Professor of Urogynaecology, King? College Hospital, London
With the exception of faulty equipment erectile dysfunction treatment home veda purchase dapoxetine 90mg online, the likelihood of which may be diminished by regular equipment servicing impotence urology generic 30 mg dapoxetine visa, treatment in the presence of contraindication erectile dysfunction caused by radiation therapy generic 60 mg dapoxetine free shipping, or at an inappropriate dose erectile dysfunction kansas city buy 90 mg dapoxetine otc, or over inappropriate body tissue would be considered an inappropriate application erectile dysfunction doctor prescription purchase dapoxetine 60mg overnight delivery. There were no reports of serious adverse events in any of the studies included in this analysis erectile dysfunction jogging cheap 60 mg dapoxetine fast delivery. Health Canada Device Licensing Documentation Health Canada reviews medical devices to assess their safety erectile dysfunction pills free trial buy cheap dapoxetine line, effectiveness and quality before being authorized for sale in Canada erectile dysfunction images purchase dapoxetine overnight. Health Canada licenses shockwave devices for their specific intended use/purpose as determined by the legal manufacturer of the device. A manual search was carried out of current and archival licenses in the Health Canada Medical Devices Active Licence Listing health-products. Also, individual devices for sale in Canada were identified and then searched in the database by company name or device name. The search yielded the following partial list of licensed devices, with manufacturer specified uses, to give the indications for which these devices have been licensed for use in Canada. Results of a search for shock wave devices licensed by Health Canada Manufacturer and Product (Health Manufacturer-stated indications Canada License Number) R. See attached Summary of Data and Effectiveness Documents, and the Medical Devices Database. Current evidence on efficacy of the procedure is inconsistent and limited in quality and quantity. Therefore this procedure should only be used with special arrangements for clinical governance, consent and audit or research. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research. Intralesional corticosteroid injection versus extracorporeal shock wave therapy for plantar fasciopathy. A systematic review of shockwave therapies in soft tissue conditions: focusing on the evidence. The effect of high energy shock waves focused on cortical bone: an in vitro study. In-vitro cell treatment with focused shockwaves Influence of the experimental setup on the sound field and biological reaction. Shockwave Therapyfor Pain Associated with Upper Extremity Orthopedic Disorders: A Review of the Clinical and Cost-Effectiveness. The Effectiveness of High-Energy Extracorporeal Shockwave Therapy Versus Ultrasound-Guided Needling Versus Arthroscopic Surgery in the Management of Chronic Calcific Rotator Cuff Tendinopathy: A Systematic Review. Extracorporeal shock wave enhanced extended skin flap tissue survival via increase of topical blood perfusion and associated with suppression of tissue pro-inflammation. Substance P and prostaglandin E2 release after shock wave application to the rabbit femur. Effects of shock waves on tenocyte proliferation and extracellular matrix metabolism. The dose-effect relationship in extracorporeal shock wave therapy: the optimal parameter for extracorporeal shock wave therapy. Extracorporeal shock-wave therapy reduces progression of knee osteoarthritis in rabbits by reducing nitric oxide level and chondrocyte apoptosis. Complications of extracorporeal shockwave therapy in plantar fasciitis: Systematic review. Neurological and/or laboratory-diagnostic tests and/or other investigations may be necessary to corroborate the diagnosis. Only a qualified physician (certified by National or International Societies) may use focused shockwave therapy to treat pathologies, which have been determined by diagnostic testing. For the treatment on bones, a high-energy, focused shockwave with positioning technology has to be used. The recommendations were assembled based on an assessment of the current published scientific and clinical information and accepted approaches to treatment. The recommendations are meant to aid the clinician in the use of shockwave medicine. In particular, the Guidelines are intended to clarify the indications and contraindications to treatment. The recommendations are not intended to be a fixed protocol, as some patients may require more or less treatment depending on the clinical scenario. To treat superficial soft tissue conditions, devices with or without focusing technology may be utilized; close attention must be paid to the depth of penetration of the shockwave source when treating deep tissue structures. Failure to maintain correct positioning could result in misdirection of the shockwave and injury to adjacent nerves or blood vessels. The high voltage power supply circuits utilized by extracorporeal shock wave systems use voltages that are capable of causing serious injury or death from electric shock. For example, this may include diseases such as gout, diabetes mellitus, rheumatoid arthritis. When a high voltage pulse from a capacitor discharge is transmitted via the slab coil, a current is induced in the aluminum -foil membrane. This acoustic lens focuses the energy of the propagated pressure wave to a small concentrated point some known distance from the lens. The shock wave passes through the lens and into a water filled coupling head (bellows). The release of shock waves is controlled by the user via the system control console, which is menu-driven. The repetition frequency of shock wave release ranges from 1Hz to 4Hz, and is adjusted by the user at the control console. Shock wave pulses are released either by manually pressing the release button on the handswitch or by holding down the release button for a preset number of pulses. Trolley with high tension capacitor charging unit and water conditioning system C. Control console with controls for system parameter setting such as energy and pulse frequency D. The coupling head provides an acoustically favorable path for the focused pressure wave as it moves from the shock head to the patient. By the law of induction, the Summary of Safety and Effectiveness Page 4 P010039 increasing current in the slab coil induces a magnetic field around the coil. Similarly, as this magnetic field builds, it induces eddy currents in the metal diaphragm (made of an aluminum -alloy disk), which, in turn, induces a magnetic field near the metal diaphragm. The magnetic field that is induced in the diaphragm has the opposite polarity of the field set up near the slab coil. Since these magnetic fields have opposite polarities, they repel each other and the diaphragm is forced away from the rigidly fixed slab coil. The resulting motion of the diaphragm creates a compression wave, which travels through the water within the shock head. Initiating the capacitive discharge is accomplished with a spark gap, which consists of two electrodes in a cavity. Water systems the water conditioning system, which has a compact design, fits with all its components in the housing of the transportable trolley. Control Console the system parameters can be controlled and displayed on the control console. This arm can be flexibly moved in three planes after releasing the electromagnetic brakes. The pain is identified by palpation by the physician or by subjective assessment of the patient. Summary of Safety and Effectiveness Page 5 P010039 the penetration depth of the therapeutic pressure pulse focus in the patient body can be set by varying the water level in the bellows. To decrease or increase the penetration depth, water is pumped into or out of the bellows. Alternate Practices and Procedures Alternative therapies can be divided into nonsurgical and surgical treatment. Among the most common initial treatments are rest and application of cold to the symptomatic region. Nonsteroidal anti-inflammatory medications including indomethacin seem to be helpful in some patients. The physical therapy modality of high-voltage electric stimulation has been helpful in relieving pain and inflammation. If the process does not respond to the above treatment choices, a cortisone injection may be appropriate. Since then, it has been available in countries other than the United States, Japan and Taiwan. The following figure (figure 2) shows the peak positive pressure at the focus as a function of Energy Level (system output range): Summary of Safety and Effectiveness Page 7 P010039 Peak Positive Pressure at the Focus 25. Animal testing Animal studies were conducted using an early prototype of the Sonocur Basic system, which used the same mechanism of electromagnetic shock-wave generation, by Rompe et. For this study, forty-two (42) New Zealand rabbits (84 total tendons) were randomized into four treatment groups: 2 1) Group A: 1000 shock-wave impulses of an energy flux of 0. In addition, there was marked histological changes with increased eosin staining, fibrinoid necrosis, fibrosis in the paratenon and infiltration of inflammatory cells. Summary of Clinical Studies As a first step in its clinical development for the U. The results also showed an efficacy advantage for the active treatment group in reducing pain at 12 weeks post-treatment compared with baseline, even though there was a higher than expected placebo effect that was consistently observed over the entire three month follow-up period. This additional testing was conducted as a multi-center clinical trial, which is described below in further detail. Study Design and Objectives the Siemens Sonocur Basic multi-center pivotal trial was a randomized, double blind (patients and evaluators), placebo-controlled, parallel treatment study. Patients with chronic tennis elbow were examined and randomized to one of two treatment groups (active, placebo). Each patient was scheduled to receive three treatments: once a week for a three-week period. The procedure for the active and placebo treatments was performed identically except that for patients receiving the placebo treatment, a sound-reflecting pad was placed between the treatment site and the shock wave head. During the study, assessments of pain level and functional activity were performed. At each visit, the pain intensity was evaluated using the Thomsen provocation test (resisted wrist extension). For this test, patients in the study were asked to score their ability to perform specific daily chores (such as opening jars/doors, washing dishes) on a scale from 1 to 10, with a score of 1 meaning that the patient had no problem at all and a score of 10 meaning that the patient could not perform the activity. Patients were scheduled for follow-up evaluations, occurring at 1-, 4-, 8-, 12 weeks, 6-months, and 12-months post-treatment. The primary analysis of the safety and efficacy data was performed after all patients were enrolled, treated, and completed their 12-week follow-up requirements. A third active treatment group patient was discontinued due to a low platelet count, which was found to be a pre-existing condition prior to study participation. The mean age for the active treatment group was 47 years (ranging from 35-71 years), and the mean age for the placebo group was 47 years (ranging from 35-60 years). Physical exam and medical histories at baseline were also similar between the treatment groups. Table 2: Patient Demographics and Treatment History Active Treatment Patients Placebo Treatment Patients Characteristic (N=56) (N=58) Age (years) Mean 47 47. Treatment Characteristics: All patients were scheduled to receive three treatments: once a week for a three week period. For all completed treatments, a maximum of 2100 impulses per treatment session was delivered for a total energy delivery of 9. The procedure for the active and placebo treatments was performed identically except that for patients receiving the placebo treatment, a sound reflecting pad was placed between the treatment site and the shock wave head. As summarized in Table 3, below, two active treatment patients had treatments aborted due to adverse patient reactions (elbow pain, nausea, diaphoresis, light headedness) and two patients (1 active, 1 placebo) had treatments interrupted due to temporary device malfunctions. Table 3: Number of patients with treatments interrupted or aborted Active (n=56) Placebo (n=58) Patients with Adverse Event 0 0 Treatments Interrupted Machine Malfunction 1 (1. For two of the three systems used in the clinical trials, device malfunctions were reported. One device malfunction was due to a broken system cable that prevented shock wave delivery, and one reported malfunction was due to a defective shock wave module that needed to be replaced (with the water cooling system cleaned and serviced). Given their low frequency of occurrence, its unlikely that these system malfunctions significantly affected the overall study results. The average pain score for patients who received the active treatment was 74 at baseline and 37. Table 4: Summary of Patient Pain Assessments from Baseline to Week 12 Treatment Baseline Week 1 Week 4 Week 8 Week 12 Group Active N 56 56 56 56 56 Mean 73. For the intent-to-treat cohort, the results show that the active treatment group had 34/56 (60. Table 1 (page 6: Adverse Device Effects of the Device on Health) summarizes the type and frequency of adverse events that were categorized as being possibly or probably related to the study treatment. The following table (Table 7) shows the occurrence of adverse events for the active treatment group that were judged to be possibly or probably treatment related over the course of the 12-month study period. Active Treatment Group: Adverse Events Through 12 Months of Follow-up Treatment Period Follow-up Period [1] Day of Treatment Between Between >12 (Treatments Treatments Treatments <=1 >1-4 >4-8 >8-12 Weeks >6-12 1, 2, 3) 1-2 2-3 Week Weeks Weeks Weeks 6 Months Months Adverse [N=56] [N=56] [N=54] [N=53] [N=51] [N=52] [N=53] [N=48] [N=46] Events # of # of # of # of # of # of # of # of # of # of patients occurrences patients patients patients patients patients patients patients patients [2] [2] [2] [2] [2] [2] [2] [2] [2] Pain 24 46 6 5 4 5 3 1 0 0 Nausea 10 10 0 0 0 0 0 0 0 0 Application 4 6 2 2 3 2 2 1 1 * Site Reaction Sweating 5 5 0 0 0 0 0 0 0 0 Dizziness 4 4 0 0 0 0 0 0 0 0 Hypertonia 2 3 1 0 2 1 1 1 0 0 Hypesthesia 3 5 0 0 0 0 0 0 0 0 Paresthesia 3 4 0 0 0 0 0 0 0 0 Joint Stiffness 1 1 1 2 1 1 1 1 1 * Myalgia 1 1 1 0 0 0 0 0 0 0 Tremor 2 2 0 0 0 0 0 0 0 0 Vasodilation 2 2 0 0 0 0 0 0 0 0 Pallor 1 1 0 0 0 0 0 0 0 0 [1] relative to the last treatment, using protocol defined windows. No new adverse events judged as being possibly or probably related to treatment were reported after the 6-month follow-up period. No additional study data is available for this patient after the 6-month follow-up period. Summary of Safety and Effectiveness Page 16 P010039 At the time of the 12-week follow-up visit, all device related adverse events had resolved, except for one patient who had moderate elbow stiffness and mild swelling that was still ongoing at the time of the 6-month follow-up visit. This patient, who had an x-ray with normal findings at baseline and 12 weeks, was unresponsive to treatment and terminated study participation soon after the 6-month follow-up visit for surgery. There were no new device related adverse effects reported during the long -term (3-12month) follow-up period. The results show a good safety profile for the system and show that the system can be used to relieve pain and improve functional activity. Chronic proximal plantar fasciitis is defined as traction degeneration of the plantar fascial band at the origin on the medial calcaneal tuberosity that has persisted for six months or more. The shock wave is generated by discharging a high voltage capacitor located in the Control Unit into a cylindrically shaped coil system in the Hand piece which is surrounded by a cylindrical metallic membrane. The transient magnetic field produced by the coil induces eddy currents in the metal membrane, causing it to repel from the coil, producing a pressure wave. The membrane is immersed in water and the pressure wave produced by the membrane propagates through the water to a concentric parabolic reflector, where it is reflected to a focal point outside of the Hand piece in front of the reflector. Instructions for cleaning and low level disinfection are provided in the Operating Instructions. The hand piece and applicator can be cleaned using a soft cloth and a general purpose surface disinfectant. Because the device is for use in intact skin only, neither high level disinfection nor sterilization are necessary. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle. Most patients with chronic proximal plantar fasciitis do not require surgery to relieve the symptoms. The use of shoe inserts (cups and pads), orthotics, oral non-steroidal anti-inflammatory agents, and local steroid injections provide pain relief in most patients. However, symptoms may persist in some patients over an extended period of time despite all forms of conservative management. However, even surgical intervention does not always result in success and could be associated with surgical complications. For the specific adverse events that occurred in the clinical studies, please see Section X below. The testing showed that typical value for the different parameters met the acceptance/performance criteria. In addition, peak positive and negative acoustic 2 pressures were also determined for the minimum flux density setting of 0. Table 1: Summary of Shock Wave Characterization Tests 2 Energy Flux Density Setting: mJ/mm 0. The study was conducted at six (6) clinical sites, all in the United States, with two (2) of the six (6) geographic sites for a single investigator. For the purpose of this study, painful heel syndrome was defined as chronic proximal plantar fasciitis that had persisted for at least 6 months before study enrollment. The patient and the clinician performing the efficacy assessments were blinded; the clinician administering the treatment (active and placebo) was not blinded. All study procedures for both groups were identical except that of the stand-off used. Active or sham procedures were administered at three (3) treatment visits approximately 1 week apart, with subsequent follow-up visits at 6 weeks, 3 months, 6 months, and 12 months after the last treatment session. The primary endpoint of comparison between the Duolith Group and Placebo Group is 3 months after the last treatment session (approximately 14 weeks after randomization). Subjects considered to be "responders" at the three (3) month follow up, continued to be followed at 6 and 12 months after the last treatment session. Clinical Inclusion and Exclusion Criteria After a screening visit to determine eligibility (Visit 1), the study started at Visit 2 with the first treatment (after randomization). Enrollment in the clinical study (G050236) was limited to patients who met the following inclusion criteria: i. Chronic proximal plantar fasciitis is defined as heel pain in the area of the insertion of the plantar fascia on the medial calcaneal tuberosity v.
It is usually mild to moderate in complicated cases so as to distinguish from other but occasionally it may be marked (haemoglobin less than hypochromic anaemias erectile dysfunction surgery dapoxetine 30mg for sale. The usual findings are as follows 6 g/dl) due to persistent and severe blood loss erectile dysfunction treatment exercises order dapoxetine line. The essential feature is a fall in due to erythroid hyperplasia (myeloid-erythroid ratio haemoglobin concentration up to a variable degree erectile dysfunction treatment in bangalore buy dapoxetine 90 mg low cost. There is normoblastic erythropoiesis chromic and microcytic erectile dysfunction pump youtube purchase dapoxetine with a mastercard, and there is anisocytosis and with predominance of small polychromatic normoblasts poikilocytosis (Fig erectile dysfunction cleveland clinic dapoxetine 30mg line. Hypochromia is due to poor filling of cytoplasm around the nucleus and a ragged and of the red cells with haemoglobin so that there is increased irregular cell border erectile dysfunction divorce 60 mg dapoxetine with mastercard. In severe cases erectile dysfunction drugs bayer proven 30mg dapoxetine, there may be only a thin so that the late normoblasts have pyknotic nucleus but rim of pink staining at the periphery erectile dysfunction green tea order dapoxetine with a visa. Target cells, elliptical persisting polychromatic cytoplasm (compared from forms and polychromatic cells are often present. Iron staining (Prussian blue reaction) macrocytic as well as microcytic hypochromic. The haematological bone marrow examination, the following biochemical tests response to parenteral iron therapy is no faster than the are of value: administration of adequate dose of oral iron but the stores i) the serum iron level is low (normal 40-140? When serum iron falls below iron, total dose is calculated by a simple formula by multi 15? The adverse effects with iron dextran raised in iron overload and is normal in anaemia of chronic include hypersensitivity or anaphylactoid reactions, disorders. These granules stain positively with Prussian preventive measures are instituted to correct the cause of blue reaction as well as stain with Romanowsky dyes when blood loss. This is iron is corrected with iron therapy as under: because the reticulocytes on release from the marrow are i) Oral therapy. Iron deficiency responds very effectively finally sequestered in the spleen to become mature red cells. These are nucleated red cells (normo absorption is obtained by giving iron fasting, but if side blasts) containing siderotic granules which stain positively effects occur. Oral iron therapy is continued long enough, both to correct the anaemia and to replenish the body iron stores. The response to oral iron therapy is observed by reticulocytosis which begins to appear in 3-4 days with a peak in about 10 days. Poor response to iron replacement may occur from various causes such as: incorrect diagnosis, non-compliance, continuing blood loss, bone marrow suppression by tumour or chronic inflammation, and malabsorption. The bone marrow cells commonly show chromosomal abnormalities, neutro penia and thrombocytopenia with associated bleeding diathesis. The spleen and liver may be either normal or mildly enlarged, while the lymph nodes are not enlarged. About 10% of individuals with refractory acquired sideroblastic anaemia develop acute myelogenous leukaemia. Drugs, chemicals and toxins: Isoniazid, an anti-tuberculous size and distribution of siderotic granules, sideroblasts may drug and a pyridoxine antagonist, is most commonly be normal or abnormal (Fig. Other granules representing iron which has not been utilised for drugs occasionally causing acquired sideroblastic anaemia haemoglobin synthesis. These cells comprise 30-50% of are: cycloserine, chloramphenicol and alkylating agents. All these agents cause reversible sideroblastic anaemia which usually resolves following Abnormal sideroblasts are further of 2 types: removal of the offending agent. Haematological disorders: these include myelofibrosis, scattered, coarse cytoplasmic granules and are seen in polycythaemia vera, acute leukaemia, myeloma, lymphoma conditions such as dyserythropoiesis and haemolysis. Miscellaneous: Occasionally, secondary sideroblastic the other type is ringed sideroblast in which haem anaemia may occur in association with a variety of inflam synthesis is disturbed as occurs in sideroblastic anaemias. The ringed arrangement of these granules is due to the presence Laboratory Findings of iron-laden mitochondria around the nucleus. Sideroblastic anaemias usually show the following haematological features: Types of Sideroblastic Anaemias 1. The acquired type is further may be microcytic, or there may be some normocytic red divided into primary and secondary forms: cells as well (dimorphic). The affected males have moderate to marked anaemia while the females are carriers of the disorder and 4. Hb electrophoresis Normal Normal Abnormal Normal Treatment tions, the anaemia is complicated by other causes such as iron, B12 and folate deficiency, hypersplenism, renal failure the treatment of secondary sideroblastic anaemia is with consequent reduced erythropoietic activity, endocrine primarily focussed on removal of the offending agent. However, in general, 2 factors appear to definite treatment is available for hereditary and idiopathic play significant role in the pathogenesis of anaemia in chronic types of sideroblastic anaemias. These are: defective red cell production and reduced administered routinely to all cases of sideroblastic anaemia red cell lifespan. Though there is abun Differential diagnosis of various types of hypochromic dance of storage iron in these conditions but the amount of anaemias by laboratory tests is summarised in Table 12. A defect in One of the commonly encountered anaemia is in patients of the transfer of iron from macrophages to the developing a variety of chronic systemic diseases in which anaemia erythroid cells in the marrow leads to reduced availability develops secondary to a disease process but there is no actual of iron for haem synthesis despite adequate iron stores, invasion of the bone marrow. In general, anaemia in chronic of erythropoieitn by inflammatory cytokines at some stage disorders is usually normocytic normochromic but can have in erythropoiesis, and hepcidin which is the key iron mild degree of microcytosis and hypochromia unrelated to regulatory hormone. Decreased survival of circulating red cells in chronic renal disease is attributed to A number of factors may contribute to the development of hyperplastic mononuclear phagocyte system. Since cell division is slow but cytoplasmic development progresses normally, the nucleated red cell precursors tend to be larger which Ehrlich in 1880 termed megaloblasts. Megaloblasts are both morphologically and functionally abnormal with the result that the mature red cells formed from them and released into the peripheral blood are also abnormal in shape and size, the most prominent abnormality being macrocytosis. Measurement of erythrocyte survival anaemia, an outline of vitamin B and folic acid metabolism 12 generally reveals mild to moderate shortening of their is given for a better understanding of the subject. Examination of the marrow generally of vitamin B12 and folic acid are summarised in Table12. Cases of chronic infection often organometallic compound having a cobalt atom situated have myeloid hyperplasia and increase in plasma cells. The only dietary sources of vitamin B12 are foods between true iron-deficiency anaemia and iron-deficient of animal protein origin such as kidney, liver, heart, muscle erythropoieisis in anemia of chronic diseases. In addition, certain other and vegetables contain practically no vitamin B unless 12 plasma proteins called phase reactants are raised in contaminated with bacteria. Cooking has little effect on its patients with chronic inflammation, probably under the activity. Body stores 2-3 mg (enough for 2-4 yrs) 10-12 mg (enough for 4 months) 304 thus, the humans are entirely dependent upon dietary sources. After ingestion, vitamin B12 in food is released and forms a stable complex with gastric R-binder. Vitamin B12 plays an important role in general action as co-enzyme, polyglutamates must be reduced to cell metabolism, particulary essential for normal dihydro and tetrahydrofolate forms. Folate exists in different plants, bacteria and 12 biochemical reactions in the body: animal tissues. Its main dietary sources are fresh green leafy vegetables, fruits, liver, kidney, and to a lesser extent, muscle Firstly, as methyl cobalamin (methyl B12) in the methylation meats, cereals and milk. Folate is labile and is largely of homocysteine to methionine by methyl tetrahydrofolate destroyed by cooking and canning. The homocysteine-methionine reaction is closely synthesised by bacteria in the human large bowel is not linked to folate metabolism (Fig. However, Secondly, as adenosyl cobalamin (adenosyl B12) in propionate absorption depends upon the form of folate in the diet. Synthetic folic Adenosyl B12 acid preparations in polyglutamate form are also absorbed Propionyl CoA > Methyl malonyl CoA > Succinyl CoA as rapidly as mono and diglutamate form because of the absence of natural inhibitors. An alternative hypothesis of inter-relationship a carrier protein, it is reconverted to polyglutamate (see of B12 and folate is the formate-saturation hypothesis. Normally, folate is lost from the sweat, Etiology and Classification of Megaloblastic Anaemia saliva, urine and faeces. It acts as a co-enzyme for 2 important bio anaemia is classified into 3 broad groups: vitamin B12 chemical reactions involving transfer of 1-carbon units (viz. This reaction is Indian Hindus and breast-fed infants have dietary lack of linked to vitamin B metabolism (Fig. Gastrectomy by lack of intrinsic factor, and small 12 these biochemical reactions are considered in detail intestinal lesions involving distal ileum where absorption of below together with biochemical basis of the megaloblastic vitamin B12 occurs, may cause deficiency of the vitamin. Deficiency of vitamin B12 takes at least 2 years to develop when the body stores are totally depleted. Folate deficiency is more often the basic biochemical abnormality common to both vitamin due to poor dietary intake. This reaction requires the presence such as methotrexate and pyrimethamine; alcohol, congenital enzyme deficiencies. In addition to the cardinal features mentioned and in various disease states, chronic alcoholism, and excess above, patients may have various other symptoms. Combined deficiency of vitamin B Laboratory Findings 12 12 and folate may occur from severe deficiency of vitamin B12 the investigations of a suspected case of megaloblastic because of the biochemical interrelationship with folate anaemia are aimed at 2 aspects: metabolism. In addition to deficiency of vitamin blood picture, red cell indices, bone marrow findings, and B and folate, megaloblastic anaemias may occasionally be biochemical tests. Based on these principles, the following scheme of investigations is followed: Clinical Features A. General Laboratory Findings Deficiency of vitamin B12 and folate may cause following clinical manifestations which may be present singly or in 1. Esti combination and in varying severity: mation of haemoglobin, examination of a blood film and evaluation of absolute values are essential preliminary 1. Typically, the patient has a smooth, beefy, red concentration may be of a variable degree. Vitamin B12 deficiency, parti cularly in patients of pernicious anaemia, is associated with macrocytosis can also be seen in several other disorders significant neurological manifestations in the form of such as: haemolysis, liver disease, chronic alcoholism, subacute combined, degeneration of the spinal cord and hypothyroidism, aplastic anaemia, myeloproliferative peripheral neuropathy (Chapter 30), while folate deficiency disorders and reticulocytosis. The underlying demonstrates marked anisocytosis, poikilocytosis and pathologic process consists of demyelination of the peripheral presence of macroovalocytes. The reticulocyte count is generally ataxia, poor finger coordination and diminished reflexes. The total white blood cell count may be be decreased and show abnormal morphology such as reduced. Presence of characteristic hypersegmented hypersegmented nuclei and agranular cytoplasm. Prussian blue staining for iron in the blood film should raise the suspicion of megaloblastic marrow shows an increase in the number and size of iron anaemia. Significant findings of marrow blood and marrow investigations and specific tests to examination are as under (Fig. The marrow is hypercellular with following biochemical abnormalities are observed in cases a decreased myeloid-erythroid ratio. Megaloblasts a result of ineffective erythropoiesis causing marrow cell are abnormal, large, nucleated erythroid precursors, breakdown. Special Tests for Cause of Specific Deficiency stains lightly, while the haemoglobinisation of the cytoplasm proceeds normally or at a faster rate i. Megaloblasts with abnormal mitoses laboratories, currently automated multiparametric, may be seen. Features of ineffective erythropoiesis such random access analysers are employed based on separa as presence of degenerated erythroid precursors may be tion techniques by chemiluminescence and enzyme-linked present. The normal Patients with pernicious anaemia have abnormal test range of vitamin B12 in serum is 280-1000 pg/ml. Assay of vitamin B12 in patients absorb vitamin B12 in water as was stipulated in blood can be done by 2 methods?microbiological assay the original Schilling test. In this test, the serum sample to causing malabsorption, the test is repeated after a course be assayed is added to a medium containing all other of treatment with antibiotics or anti-inflammatory drugs. The medium along with another way of distinguishing whether megaloblastic microorganism is incubated and the amount of vitamin anaemia is due to cobalamine or folate is by serum B12 is determined turbimetrically which is then compared determination of methylmalonic acid and homocysteine with the growth produced by a known amount of vitamin by sophisticated enzymatic assays. Several organisms have been used for this test such cobalamine deficiency, while in folate deficiency there is as Euglena gracilis, Lactobacillus leichmannii, Escherichia coli only elevation of homocysteine and not of methylmalonic and Ochromonas malhamensis. Values of 4 ng/ml or less are generally considered to be diagnostic of folate ii) Radioassay. These tests are more sensitive and have the formerly for assessing folate status but it is less specific advantage over microbiologic assays in that they are and less sensitive than the serum assays. Radioisotope used for labeling B12 is either Co 57 estimated by 2 methods?microbiological assay and or Co. Other pathologic changes are Most cases of megaloblastic anaemia need therapy with secondary to vitamin B deficiency and include 12 appropriate vitamin. This includes: hydroxycobalamin as megaloblastoid alterations in the gastric and intestinal intramuscular injection 1000? Blood transfusion should be avoided the disease has insidious onset and progresses slowly. Packed cells may, clinical manifestations are mainly due to vitamin B12 however, be infused slowly. These include: anaemia, glossitis, neurological Treatment of megaloblastic anaemia is quite gratifying. Reticulo hepatosplenomegaly, congestive heart failure and cytosis appears within 4-5 days after therapy is started and haemorrhagic manifestations. Haemoglobin should rise by 2-3 g/dl each such as autoimmune thyroiditis may be associated. The peripheral neuropathy may show some improvement but subacute combined degeneration of the Diagnostic Criteria spinal cord is irreversible. The condition ii) Megaloblastic anaemia in bone marrow examination, is, therefore, also termed Addisonian megaloblastic anaemia. Minor clinical criteria: by an autoimmune reaction against gastric parietal cells. Reference standard criteria: thyroiditis, vitiligo, diabetes and idiopathic adrenocortical i) Schilling test showing malabsorption of oral cyano insufficiency. Most of the abnormalities due to vitamin B12 deficiency Extravascular haemolysis is more common than the can be corrected except the irreversible damage to the spinal former. Corticosteroid therapy can improve the gastric lesion pathogenesis of various haemolytic anaemias. Acquired haemolytic anaemias caused by a variety of extrinsic environmental factors (extracorpuscular). Hereditary haemolytic anaemias are usually the result of intrinsic red cell defects (intracorpuscular). Haemolytic anaemias are defined as anaemias resulting from an increase in the rate of red cell destruction. These are briefly haemoglobin is not liberated into the plasma in appreciable described below: amounts. However, clinical features common to most congenital and acquired shortening of red cell lifespan does not necessarily result in haemolytic anaemias are as under: anaemia. Positive family history with life-long anaemia in patients causing anaemia to the patient, so-called compensated with congenital haemolytic anaemia. Mild fluctuating jaundice due to unconjugated anaemia may occur by 2 mechanisms: hyperbilirubinaemia. Urine turns dark on standing due to excess of Firstly, the red cells undergo lysis in the circulation and urobilinogen in urine. Splenomegaly is found in most chronic haemolytic In these cases the plasma haemoglobin rises substantially anaemias, both congenital and acquired. In extravascular haemolysis, plasma Pathways by which haemoglobin derived from effete red cells haemoglobin level is, therefore, barely raised. Reticulocyte count reveals reticulocytosis which is generally early and is hence most useful initial test of marrow B. Disorders of red cell interior morphological appearances of red cells described on page 366 and illustrated in Fig. Target cells (Leptocytes) Increased ratio of surface area: volume Thalassaemias Liver disease HbS disease HbC disease 3. Isoimmune haemolytic anaemia in which the antibodies are whenever present, corticosteroid therapy, and in severe cases acquired by blood transfusions, pregnancies and haemolytic blood transfusions. The haematological and detection of incomplete Rh-antibodies in saline directly biochemical findings in such cases are as under: (direct Coombs) or after addition of albumin (indirect 1. Positive direct Coombs (antiglobulin) test for presence of warm antibodies on the red cell, best detected at 37?C. Warm antibodies reactive at body may indicate presence of large quantities of warm temperature and coating the red cells are generally IgG class antibodies in the serum. In more severe cases, haemoglobinaemia and lost resulting in spherical transformation of the red cells haemoglobinuria may be present. Antibodies which are reactive in the cold spleen is particularly efficient in trapping red cells coated (4?C) may induce haemolysis under 2 conditions: cold with IgG antibodies. It is, thus, the major site of red cell agglutinin disease and paroxysmal cold haemoglobinuria. These cold antibodies are usually directed against the I any apparent cause (idiopathic) but about a quarter of antigen on the red cell surface. Most cold agglutinins affect usual clinical features are as follows: juvenile red blood cells. It is seen In each type of drug-induced immunohaemolytic 313 in the course of certain infections. Mycoplasma anaemia, discontinuation of the drug results in gradual pneumonia, infectious mononucleosis) and in lymphomas. Cyanosis affecting the cold exposed regions such as tips characterised by red cell fragmentation (schistocytosis). Direct external trauma to red Treatment consists of keeping the patient warm and blood cells when they pass through microcirculation, espe treating the underlying cause.
During later stages of shock erectile dysfunction cholesterol lowering drugs dapoxetine 60 mg otc, serious ischaemic damage with loss of cortical functions erectile dysfunction genetic purchase dapoxetine once a day, anoxia damages the capillary and venular wall and arteioles coma impotence over 70 buy dapoxetine cheap, and a vegetative state erectile dysfunction treatment chinese medicine proven 30mg dapoxetine. Vasodilatation results in peripheral pooling Grossly impotence restriction rings generic dapoxetine 30 mg amex, the area supplied by the most distal branches of of blood which further deteriorate the effective circulating the cerebral arteries suffers from severe ischaemic necrosis blood volume erectile dysfunction filthy frank purchase dapoxetine visa. In shock due to burns erectile dysfunction vacuum device buy dapoxetine with visa, Purkinje cells diabetes and erectile dysfunction causes order dapoxetine without prescription, are more prone to develop the effects of acute stress ulcers of the stomach or duodenum may occur ischaemia. Grossly, the lesions are multifocal and widely distributed Dead and dying nerve cells are replaced by gliosis. There Microscopically, the involved surface of the bowel shows are 2 types of morphologic changes in heart in all types of dilated and congested vessels and haemorrhagic necrosis shock: of the mucosa and sometimes submucosa. There may be small or large infection may supervene and condition may progress into ischaemic areas or infarcts, particularly located in the pseudomembranous enterocolitis. Microscopically, depending upon the time lapse between injury and cell death, ischaemic shrinkage, hydropic 3. Lungs due to dual blood supply are change, focal necrosis, or fatty change may be seen. Liver generally not affected by hypovolaemic shock but in septic function may be impaired. Other organs such as lymph nodes, spleen and pancreas may also show foci of necrosis in Grossly, the lungs are heavy and wet. The renal ischaemia following Shallow and sighing respiration In addition, the patients in shock have pale face, sunken systemic hypotension is considered responsible for renal eyes, weakness, cold and clammy skin. The end-result is generally anuria and Life-threatening complications in shock are due to death. Sectioned responses and activation of various cascades (clotting, surface shows blurred architectural markings. These include the following*: Microscopically, the tubular lesions are seen at all levels 1. The Thrombosis is the process of formation of solid mass in hypoperfusion of the alimentary tract in conditions such circulation from the constituents of flowing blood; the mass as shock and cardiac failure may result in mucosal and itself is called a thrombus. In contrast, a blood clot is the mass mural infarction called haemorrhagic gastroenteropathy of coagulated blood formed in vitro. These events are discussed below: formed in healthy individuals at the site of bleeding. In other words, haemostatic plug wall is important for maintaining normal blood flow. An at the cut end of a blood vessel may be considered the intact endothelium has the following functions: simplest form of thrombosis. Haemostatic plugs are useful as they stop the escape of blood and plasma, whereas thrombi i) It protects the flowing blood from the thrombogenic developing in the unruptured cardiovascular system may influence of subendothelium. Since the protective haemostatic plug formed as a result of normal haemostasis is an example of thrombosis, it is iii) It can release a few prothrombotic factors which have procoagulant properties (thrombosis favouring factors). Human beings possess inbuilt system by which the blood remains in fluid state normally and guards against the b) von Willebrand factor that causes adherence of platelets to the subendothelium. However, injury c) Platelet activating factor which is activator and to the blood vessel initiates haemostatic repair mechanism aggregator of platelets. B, Endothelial injury exposes subendothelium, initiating adherence of platelets and activation of coagulation system. D, Activated coagulation system forms fibrin strands in which are entangled some leucocytes and red cells and a tight meshwork is formed called thrombus. A, Normal non-activated platelet, having open canalicular system and the cytoplasmic organelles dispersed in the cell. B, Early adhesion phase, showing dilatation of the canalicular system with formation of pseudopods and the organelles present in the centre of the cell. A number of factors and conditions may the phospholipid complex-platelet factor 3 gets activated cause vascular injury and predispose to the formation of which plays important role in the intrinsic pathway of thrombi. Following endothelial cell injury, both haemostatic process and thrombus formation. The sequence of events is as under (blood) pathway, the extrinsic (tissue) pathway, and the (Fig. The blood is kept in fluid down, the blood cells including platelets marginate to the state normally and coagulation system kept in check by periphery and form a kind of pavement close to endothelium controlling mechanisms. These act on coagulation factors so as allows a higher release of oxygen from the blood, turbulence to oppose the formation of thrombin. Plasmin, a potent fibrinolytic enzyme, is formed by the action of plasminogen activator on plasminogen present in the normal plasma. The platelets are present in the slow-moving laminar stream adjacent to the central stream while the peripheral stream consists of most slow-moving cell-free plasma close to endothelial layer (Fig. The effect of hypercoagulability on Thrombosis may occur in the heart, arteries, veins and the thrombosis is favoured by advancing age, smoking, use of capillaries. Hypercoagulability may formation at these sites, the clinical effects of these are even occur by the following changes in the composition of blood: more different. Arterial A number of primary (genetic) and secondary (acquired) factors favour thrombosis. Mixed or laminated Primary (Genetic) factors: thrombi are also common and consist of alternate white i) Deficiency of antithrombin and red layers called lines of Zahn. Red thrombi are soft, ii) Deficiency of protein C or S red and gelatinous whereas white thrombi are firm and iii) Defects in fibrinolysis iv) Mutation in factor V pale. Microscopically, the composition of thrombus is deter Secondary (acquired) factors: mined by the rate of flow of blood i. The lines of Zahn are formed by ii) Prolonged bed-rest iii) Immobilisation alternate layers of light-staining aggregated platelets iv) Cigarette smoking admixed with fibrin meshwork and dark-staining layer of red cells. Red (venous) thrombi have more abundant b) Clinical conditions predisposing to thrombosis: red cells, leucocytes and platelets entrapped in fibrin i) Heart diseases. Thus, red thrombi closely resemble blood clots rheumatic mitral stenosis, cardiomyopathy) ii) Vascular diseases. The thrombus is adherent to the arterial wall and is seen occluding most of the lumen. It shows lines of Zahn composed of granular-looking platelets and fibrin meshwork with entangled red cells and leucocytes. Relation to vessel wall Adherent to the vessel wall Weakly attached to the vessel wall 3. Shape May or may not fit their vascular contours Take the shape of vessel or its bifurcation 4. Microscopy the surface contains apparent lines of Zahn the surface is chicken fat yellow covering the underlying red currant jelly Origin of Thrombi v) Superior vena cava: infections in head and neck. Thrombi may arise from the heart, arteries, veins or in vi) Inferior vena cava: extension of thrombus from hepatic vein. They are more Distinguishing features between thrombi formed in common in the atrial appendages, especially of the right rapidly-flowing arterial circulation and slow-moving venous atrium, and on mitral and aortic valves called vegetations blood are given in Table 5. Cardiac thrombi are of packed red cells are formed in the capillaries in acute mural (non-occlusive) as are the mural thrombi encountered inflammatory lesions, vasculitis and in disseminated in the aorta in atherosclerosis and in aneurysmal dilatations. Rarely, large round thrombus may form and obstruct the mitral valve and is called ball-valve thrombus. Agonal thrombi Fate of Thrombus are formed shortly before death and may occur in either or the possible fate of thrombi can be as under (Fig. The examples of system with consequent release of plasmin which may major forms of vascular thrombi are as under: dissolve the thrombus completely resulting in resolution. Arterial thrombi: Usually, lysis is complete in small venous thrombi while large i) Aorta: aneurysms, arteritis. Phagocytic cells (neutrophils and vi) Cerebral artery: atherosclerosis, vasculitis. The proteolytic enzymes liberated by leucocytes i) Veins of lower limbs: deep veins of legs, varicose veins. Capillaries ii) Popliteal, femoral and iliac veins: postoperative stage, grow into the thrombus from the site of its attachment and postpartum. Blood flow Formed in rapidly-flowing blood of arteries and heart Formed in slow-moving blood in veins 2. Sites Common in aorta, coronary, cerebral, Common in superficial varicose veins, deep leg iliac, femoral, renal and mesenteric arteries veins, popliteal, femoral and iliac veins 3. Thrombogenesis Formed following endothelial cell injury Formed following venous stasis. Development Usually mural, not occluding the lumen completely, Usually occlusive, take the cast of the vessel in may propagate which formed, may propagate in both directions 5. Macroscopy Grey-white, friable with lines of Zahn on surface Red-blue with fibrin strands and lines of Zahn 6. Microscopy Distinct lines of Zahn composed of platelets, fibrin Lines of Zahn with more abundant red cells with entangled red and white blood cells 7. The new vascular channels in it may be able to re-establish the blood flow, Definition and Types called recanalisation. The fibrosed thrombus may undergo Embolism is the process of partial or complete obstruction of hyalinisation and calcification. The thrombus may enlarge in size due detached from its site of origin is called an embolus. Most to more and more deposition from the constituents of flowing usual forms of emboli (90%) are thromboemboli i. In this way, it may ultimately cause obstruction of originating from thrombi or their parts detached from the some important vessel. The thrombi in early stage and infected thrombi are quite friable and may get detached from A. These depend upon the site of thrombi, rapidity of formation, and nature of thrombi. Large thrombi in the heart may cause sudden death by mechanical obstruction of blood flow or ii) Septic, when infected. These cause ischaemic necrosis of the i) Cardiac emboli from left side of the heart. Sudden originating from atrium and atrial appendages, infarct in the death may occur following thrombosis of coronary artery. Depending upon the flow of blood, two special types v) Painful thrombosed veins (thrombophlebitis) of emboli are mentioned: vi) Painful white leg (phlegmasia alba dolens) due to i) Paradoxical embolus. An embolus which is carried from ileofemoral venous thrombosis in postpartum cases the venous side of circulation to the arterial side or vice versa vii) Thrombophlebitis migrans in cancer. Pulmonary embolism Veins of lower legs of lodgement, and adequacy of collateral circulation. Systemic embolism Left ventricle (arterial) vascular occlusion occurs, the following ill-effects may result: 3. Fat embolism Trauma to bones/soft tissues i) Infarction of the organ or its affected part. Air embolism Venous: head and neck necrosis in the lower limbs (70-75%), spleen, kidneys, brain, operations, obstetrical trauma intestine. Arterial: cardiothoracic ii) Gangrene following infarction in the lower limbs if the surgery, angiography collateral circulation is inadequate. Decompression Descent: divers sickness Ascent: unpressurised flight iii) Arteritis and mycotic aneurysm formation from bacterial 6. Atheroembolism Atheromatous plaques iv) Myocardial infarction may occur following coronary 8. An embolus which travels against the flow of blood is called retrograde embolus. The spread the following sources: occurs by retrograde embolism through intraspinal veins i) Thrombi in the veins of the lower legs are the most which carry tumour emboli from large thoracic and common cause of venous emboli. Some of the important types of embolism are tabulated iv) Thrombosis in cavernous sinus of the brain. The most significant effect of venous embolism is Thromboembolism obstruction of pulmonary arterial circulation leading to A detached thrombus or part of thrombus constitutes the pulmonary embolism described below. Pulmonary embolism is the most common be derived from the following sources: and fatal form of venous thromboembolism in which there A. Causes within the heart (80-85%): these are mural is occlusion of pulmonary arterial tree by thromboemboli. Causes within the arteries: these include emboli develop thromboembolism is tabulated in Table 5. Pulmonary emboli are more common in hospitalised or bed-ridden patients, though they can occur in ambulatory patients as well. The causes are as follows: i) Thrombi originating from large veins of lower legs (such as popliteal, femoral and iliac) are the cause in 95% of pulmonary emboli. Detachment of thrombi from any of the above-mentioned sites produces a thrombo-embolus that flows through venous drainage into the larger veins draining into right side of the heart. If the thrombus is large, it is impacted at the bifurcation of the main pulmonary artery (saddle embolus), or may be found in the right ventricle or its outflow tract. Gross appearance Head pale, tail red No distinction in head and tail; smooth surface dry dull surface 5. Microscopy Platelets and fibrin in layers, Mixed with blood clot, Lines of Zahn seen lines of Zahn rare are then impacted in a number of vessels, particularly iii) Pulmonary infarction. The clinical features include chest pain embolus from right heart into the left heart through atrial or due to fibrinous pleuritis, haemoptysis and dyspnoea due ventricular septal defect. The clinical features are haemoptysis, Pulmonary embolism occurs more commonly as a compli dyspnoea, and less commonly, chest pain due to central cation in patients of acute or chronic debilitating diseases location of pulmonary haemorrhage. Women in their reproductive period are at higher risk such as in late be concomitant pulmonary infarction. The effects of pulmonary embolism depend mainly on (60-80%) are resolved by fibrinolytic activity. These patients the size of the occluded vessel, the number of emboli, and are clinically silent owing to bronchial circulation so that lung on the cardiovascular status of the patient. These are the sequelae of instantaneous death, without occurrence of chest pain or multiple small thromboemboli undergoing healing rather dyspnoea. Numerous small emboli may this is the type of arterial embolism that originates comm obstruct most of the pulmonary circulation resulting in acute only from thrombi in the diseased heart, especially in the right heart failure. These arterial emboli invariably cause infarction at the sites of lodgement which include, in descending order of frequency, lower extremity, brain, and internal visceral organs (spleen, kidneys, intestines). Thus, the effects and sites of arterial emboli are in striking contrast to venous emboli which are often lodged in the lungs. Fat Embolism Obstruction of arterioles and capillaries by fat globules constitutes fat embolism. If the obstruction in the circulation is by fragments of adipose tissue, it is called fat-tissue embolism. Following are the important causes of fat embolism: i) Traumatic causes: Trauma to bones is the most common cause of fat embolism Figure 5. The pathologic findings in the brain are Diabetes mellitus petechial haemorrhages on the leptomeninges and minute Fatty liver haemorrhages in the parenchyma. Pancreatitis Microscopically, microinfarct of brain, oedema and Sickle cell anaemia haemorrhages are seen. Renal fat embolism present in the glomerular Extrinsic fat or oils introduced into the body. The following mechanisms are proposed Other effects include tubular damage and renal to explain the pathogenesis of fat embolism. Besides the brain and kidneys, other findings in systemic fat embolism are petechiae in the skin, i) Mechanical theory. Mobilisation of fluid fat may occur conjunctivae, serosal surfaces, fat globules in the urine following trauma to the bone or soft tissues. Some of the fat globules may further pass through into the systemic circulation to lodge in other organs. Air, nitrogen and other gases can produce bubbles within the circulation and obstruct the blood vessels causing damage ii) Emulsion instability theory. Two main forms of gas embolism?air embolism pathogenesis of fat embolism in non-traumatic cases. According to this theory, fat emboli are formed by aggrega tion of plasma lipids (chylomicrons and fatty acids) due to Air Embolism disturbance in natural emulsification of fat. Air embolism occurs when air is introduced into venous or iii) Intravascular coagulation theory. The blood vessels of lungs are chemically injured by high plasma accidental opening of a major vein of the neck like jugular, levels of free fatty acid, resulting in increased vascular or neck wounds involving the major neck veins, may allow permeability and consequent pulmonary oedema. During childbirth by embolism depend upon the size and quantity of fat globules, normal vaginal delivery, caesarean section, abortions and and whether or not the emboli pass through the lungs into other procedures, fatal air embolism may result from the the systemic circulation. Air embolism tures of bones, presence of numerous fat emboli in the may occur during intravenous blood or fluid infusions if only capillaries of the lung is a frequent autopsy finding because positive pressure is employed. During angiographic procedures, air may obstruction of pulmonary circulation due to extensive be entrapped into a large vein causing air embolism. The effects of venous air embolism depend upon the following factors: Microscopically, the lungs show hyperaemia, oedema, i) Amount of air introduced into the circulation. This results in similar effects as in 123 as little as 40 ml of air may have serious results. The effects of decompression sickness depend in the pulmonary arterial trunk in the right heart. If bubbles upon the following: of air in the form of froth pass further out into pulmonary Depth or altitude reached arterioles, they cause widespread vascular occlusions. If Duration of exposure to altered pressure death from pulmonary air embolism is suspected, the heart Rate of ascent or descent and pulmonary artery should be opened in situ under water General condition of the individual so that escaping froth or foam formed by mixture of air and Pathologic changes are more pronounced in sudden blood can be detected. Entry of air into pulmonary those who decompress from low pressure to normal levels. Acute form occurs due to acute obstruction of small blood ii) Paradoxical air embolism.
Prior to the study erectile dysfunction vacuum pumps reviews purchase dapoxetine 60mg free shipping, 9 gastric banding patients and 10 lifestyle patients had metabolic syndrome beta blocker causes erectile dysfunction order dapoxetine 90mg free shipping. At 24 month follow-up erectile dysfunction psychological causes treatment buy dapoxetine 60mg amex, none of the patients in the gastric banding group had the metabolic syndrome compared with 4 in the lifestyle group erectile dysfunction ugly wife cheap dapoxetine 30 mg amex. The authors concluded that use of gastric banding compared with lifestyle intervention resulted in a greater percentage of excess weight loss erectile dysfunction drugs market order 60mg dapoxetine mastercard. All patients completed a 1 year follow-up with 41 patients completing 2 year follow-up erectile dysfunction meds online order discount dapoxetine on-line. The estimated weight loss at 6 months was 31 16; at 1 year 46 21; and 2 years 47 22 erectile dysfunction fpnotebook order generic dapoxetine. At follow-up erectile dysfunction drugs research buy dapoxetine 90 mg cheap, 47 of the 85 identified co morbidities (55%) were completely resolved and 25 (29%) were improved in comparison with baseline. Improvements in alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, fasting insulin, triglycerides, and high density lipoprotein, were also seen. The authors concluded that based on these results, laparoscopic adjustable banding is an appropriate surgical option for morbidly obese adolescents. Surgical patients showed significant improvements in triglycerides (-65 mg/dL), total cholesterol (-28 mg/dL), fasting blood glucose (-12 mg/dL), and fasting insulin (-21 microM/mL]). The authors concluded that post-operatively, adolescents lose significant weight and realize major metabolic improvements. Complication rates and types are similar to those of adults; however, the small sample size of this precludes calculation of complication rates. There was one causally related adverse event with StomaphyX, that required laparoscopic exploration and repair. Seventeen of 20 (85%) patients had an average reduction in stoma diameter of 16 mm (65% reduction) and an average reduction in pouch length of 2. Laparoscopic Mini-Gastric Bypass (One Anastomosis Gastric Bypass) In a prospective, observational and descriptive study of 150 morbidly obese patients who underwent laparoscopic one anastomosis gastric bypass, lipid profiles were evaluated preoperatively and at different intervals during a 2-year follow-up. Long-term randomized studies are needed to fully evaluate the impact of this procedure. Long-term outcomes (up to 11 years) in a cohort of 156 patients undergoing silastic ring mini gastric bypass were evaluated by Sheikh et al. Computer-based hospital information was available on a total of 139 patients; 92 patients responded to the follow-up questionnaires. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. Gastric Electrical Stimulator Lebovitz (2016) reviewed interventional treatment of obesity and type 2 diabetes with gastric electrical stimulation. Combining lifestyle modification with gastric electrical stimulation frequently complicates the interpretation of the results and requires that the studies be double blind and inactive implanted device controlled. The relationship between the metabolic benefits of gastric electrical stimulation in improving glycemic control and lowering systolic blood pressure needs further analysis through randomized controlled studies. No statistical difference in the weight loss between study and control groups was found at six-month follow-up. At the 12-month follow-up point, 71% of participants lost weight (54% lost > 10% of excess, and 29% lost > 20% excess). Thirty-one studies consisting of a total of 33 different trials were included in the systematic review for data analysis. Weight loss was achieved in most studies, especially during the first 12 mo, but only very few studies had a follow-up period longer than 1 year. Among those that had a longer follow-up period, many were from the Transcend (Implantable Gastric Stimulation) device group and maintained significant weight loss. Other significant results included changes in appetite/satiety, gastric emptying rate, blood pressure and neurohormone levels or biochemical markers such as ghrelin or HbA1c respectively. Vagus Nerve Blocking the ReCharge pivotal study sponsored by the manufacturer (Ikramuddin et al. Subjects randomized to the sham control group underwent a surgical procedure consisting of anesthesia, implantation of a non-functional neuroregulator, and the same number of incisions an investigator would use during the laparoscopic placement of the leads. The use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified co-primary efficacy objectives which were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. Heartburn/dyspepsia and implant site pain were the most frequently reported adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Study subjects consisted of 90% females, body mass index of 41 1 kg/m2, and age of 46 1 years. Electrodes were implanted laparoscopically on both vagi near the esophago-gastric junction to provide electrical block. They noted that these findings have resulted in the design and implementation of a randomized, double-blind, prospective, multi-center trial in an obese subject population. Well-designed studies are needed to determine the best usage of the Maestro Rechargeable System. Gastric ulcers were observed; a minor device change led to significantly reduced ulcer size and frequency (10%). The authors concluded that the dual balloon system was significantly more effective than diet and exercise in causing weight loss with a low adverse event profile. On the other hand, complications of intragastric balloon placement occurred, however few of a serious nature. These patients refused bariatric surgery because of fear of complications and mortality and were followed over a 6 to 30 month period (mean 18. The authors concluded that use of the intragastric balloon served as a first step and a smooth introduction to bariatric surgery for morbidly obese patients who initially refused surgical intervention; however; the incidence of surgical intervention was double in patients who initially experienced the benefits of weight loss and then had obesity recurrence, compared with patients in whom the method failed. However, there is not sufficient evidence confirming its safety or long-term efficacy. The authors evaluation is that intragastric balloons are the best-studied of all the treatments and although they show 30%-50% excess weight loss after device removal, there is a lack of significant long-term follow-up. More severe, albeit rare, events have occurred included gastric outlet or intestinal obstruction caused by underinflated or leaking balloon, dehydration, gastric perforation with sepsis, aspiration pneumonia, abdominal cramping, and infection (fluid inside balloon positive for Candida albicans) (Hayes, 2015). Nine subjects required a prolonged hospital stay and three subjects required major interventions. The authors concluded that duodenojejunal bypass liner promotes a more significant weight loss beyond a minimal sham effect in candidates for bariatric surgery. This study is limited by small patient sample, short term follow-up and relatively high complication rates. Secondary outcomes included changes in blood pressure, lipids, and anti-diabetic medication. Initial C-peptide levels and body weight may help to select patients with the greatest chance of success. They found that the Endobarrier in in this subset of patients is associated with significant weight decrease and moderate reduction in HbA1c at month 12. Significant weight-loss and a reduced body composition resulted from either procedure vs. Intergroup comparisons for glycemic parameters yielded no statistically significant differences. The comorbidities including diabetes, sleep apnea and hypertension were markedly improved in the both groups after surgery. Eligible studies included one randomized controlled trial and three non-randomized controlled trials involving 299 patients. The difference in the resolution of diabetes mellitus between these two approaches did not reach statistical significance (p=0. At 52 weeks, participants in the AspireAssist group, on a modified intent-to-treat basis, had lost a mean (?s. The most frequently reported adverse events were abdominal pain and discomfort in the perioperative period and peristomal granulation tissue and peristomal irritation. Outcomes of the post approval study may provide more solid evidence regarding the longer term efficacy of the AspireAssist. Ten of the 11 subjects who underwent aspiration therapy and 4 of the 7 subjects who underwent lifestyle therapy completed the first year of the study. Seven of the 10 subjects in the aspiration therapy group completed an additional year of therapy and maintained a 20. Noren and Forssel (2017) reported 1 and 2-year outcomes from their prospective observational study of 25 obese subjects to evaluate weight reduction and safety of aspiration therapy with AspireAssist. This weight loss surpassed our expectation and is nearly at the level of gastric bypass procedure and other major abdominal surgery for obesity. No clinically significant changes in serum potassium or other electrolytes occurred. For example, the complicated vascular anatomy of the stomach and its rich supply of collateral vessels creates a technical challenge to administer either small particle or liquid embolics without non-target embolization and resultant tissue damage in a population of patients without a terminal illness. Hunger/appetite scores decreased in the first 2 weeks after the procedure and then rose without reaching preprocedure levels. Further expansion of this study will provide more insight into the long-term safety and efficacy of bariatric embolization. They commented that the development of a variety of new endoscopic therapies that replicate the physiological benefits of bariatric surgery in a safe, cost-effective, and minimally invasive fashion may potentially offer the best path to making a meaningful impact on the obesity epidemic, as less than 1% of qualified patients actually undergo bariatric surgery. Currently investigated devices have established promising outcomes in short-term weight loss and in control of the metabolic and other medical adverse events of obesity. Further studies will help define their optimal role in the comprehensive management of obesity. Causative factors to note include a family history of obesity, use of weight-gaining medications, and dietary and physical activity patterns. A brief summary of personal weight loss attempts, commercial plans, and physician-supervised programs should be reviewed and documented, along with the greatest duration of weight loss and maintenance. The detailed evidence-based recommendations allow for nuanced clinical decision-making that addresses real world medical care of patients with obesity, including screening, diagnosis, evaluation, selection of therapy, treatment goals, and individualization of care. The goal is to facilitate high-quality care of patients with obesity and provide a rational, scientific approach to management that optimizes health outcomes and safety. The need to ensure that post-operative psychosocial care is available has been noted in established practice guidelines and evidence suggests that such care is associated with better outcomes after surgery. More prospective studies with longer follow-up are required to establish the clinically significant efficacy and patient tolerance of this device. The associated risk/benefit analysis should also include the consideration of the potential long-term health risks of untreated or inadequately treated obesity for the individual candidate. Although evidence suggests that certain parameters associated with childhood obesity are linked to the development of the metabolic syndrome in adulthood, the diagnosis of the metabolic syndrome in this age group is ill-defined and not well standardized. Therefore, a diagnosis of the metabolic syndrome in obese adolescents is a relative indication for bariatric surgery. Providing access to bariatric surgery earlier in life when the disease burden and severity is lower might decrease the operative risk, morbidity, and mortality. Additionally, earlier surgical intervention alters the natural course of many obesity-related co-morbidities that otherwise would put the patient at risk of long-term complications and early mortality. Although current short-term data show improvement in depression, eating disturbances, and quality of life after weight loss induced by bariatric surgery, the long-term results have not been well studied. The presence of such eating disturbances before bariatric surgery does not appear to affect weight loss outcome after bariatric surgery in adult cohorts, at least in the short term. Therefore, although not studied specifically in adolescents seeking bariatric surgery, the presence of eating disturbances is not an exclusion criterion. If an eating disorder is identified, treatment should be initiated and the patient should be considered stable before bariatric surgery. Additional surgical therapy may benefit patients who present with insufficient weight loss, continued co-morbid disease, or weight gain after bariatric surgery. As the risks of reoperative bariatric surgery are higher than with the primary procedure, evidence suggests the need for careful patient selection. The Task Force also conducted a systematic review to evaluate morbidity, mortality, and weight loss outcomes after reoperative bariatric surgery. However, not all reoperations will result in further weight loss or resolution of comorbidity. Endocrine Society In its 2016 guideline for the prevention and treatment of pediatric obesity (August et al. They do not make a definitive recommendation for one procedure over another and note that at the present time, decisions are driven by patient and surgeon preferences, as well as considerations regarding the degree and timing of necessary outcomes versus tolerance of risk and lifestyle change. Further, the 2008 guidelines state that there are no absolute contraindications to bariatric surgery. Relative contraindications to surgery may include severe heart failure, unstable coronary artery disease, end-stage lung disease, active cancer diagnosis/treatment, cirrhosis with portal hypertension, uncontrolled drug or alcohol dependency, and severely impaired intellectual capacity. It is to be used in conjunction with a long-term supervised diet and behavior modification program designed to increase the likelihood of significant long-term weight loss and weight loss maintenance. It is indicated for adults who have failed conservative weight reduction strategies, such as supervised diet, exercise and behavior modification program. The device was changed to add a silicone adhesive to bond the strain relief sleeve and the locking connector components of the injection port. Surgical stapling devices are used in all bariatric surgical procedures except gastric banding. The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome. Endocrine Society releases new clinical practice guideline on the prevention and treatment of pediatric obesity. Body composition and bone health in adolescents after Roux-en-Y gastric bypass for severe obesity. Weight reduction and improvement in diabetes by the duodenal-jejunal bypass liner: a 198 patient cohort study. Outcomes associated with pre-operative weight loss after laparoscopic Roux-en-Y gastric bypass. Systematic review of sleeve gastrectomy as staging and primary bariatric procedure. Systematic review on reoperative bariatric surgery: American Society for Metabolic and Bariatric Surgery Revision Task Force. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003-2012. Early trial data show novel, less invasive weight-loss treatment is safe and efficacious. StomaphyX vs a sham procedure for revisional surgery to reduce regained weight in Roux-en-Y gastric bypass patients : a randomized clinical trial. Laparoscopic sleeve gastrectomy as first-line surgical treatment for morbid obesity among adolescents. Indications for revisions following 630 consecutive laparoscopic sleeve gastrectomy cases: Experience in a single accredited center. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. Weight loss, weight regain, and conversions to Roux-en-Y gastric bypass: 10-year results of laparoscopic sleeve gastrectomy. Prevalence of overweight, obesity, and extreme obesity among adults: United States, 1960?1962 Through 2011?2012. Long-term outcome after laparoscopic sleeve gastrectomy in patients over 65 years old: a retrospective analysis. Open-label, sham-controlled trial of an endoscopic duodenojejunal bypass liner for pre-operative weight loss in bariatric surgery candidates. Managing complications associated with laparoscopic Roux-en-Y gastric bypass for morbid obesity. Health care guideline: prevention and management of obesity (mature adolescents and adults). Thromboembolic events in bariatric surgery: a large multi-institutional referral center experience. A multidisciplinary approach to laparoscopic sleeve gastrectomy among multiethnic adolescents in the United States. Pre-operative assessment and perioperative care of patients undergoing bariatric surgery. Vertical gastrectomy for morbid obesity in 216 patients: report of two-year results. Comparing outcomes of two types of bariatric surgery in an adolescent obese population: Roux-en-Y gastric bypass vs. A primer on natural orifice transluminal endoscopic surgery: building a new paradigm. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient?2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Laparoscopic adjustable gastric banding for morbidly obese adolescents affects android fat loss, resolution of co-morbidities, and improved metabolic status. Think tank on enhancing obesity research at the National Heart, Lunch and Blood Institute. Short-term outcomes of laparoscopic gastric plication in morbidly obese patients: importance of post-operative follow-up. Assessment of weight loss with the intragastric balloon in patients with different degrees of obesity. Laparoscopic adjustable gastric banding in severely obese adolescents: A Randomized Trial. American Society for Metabolic and Bariatric Surgery Clinical Issues Committee vagal blocking therapy for obesity. American Society for Metabolic and Bariatric Surgery integrated health nutritional guidelines for the surgical weight loss patient 2016 update: micronutrients.
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