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Dietary magnesium intake influences exercise capacity and hematologic parameters in rats.

The effects of feeding varying concentrations of dietary Mg (50, 100, 200, or 400 ppm) for 22 days on exercise capacity and hematologic parameters were investigated in male rats. Five-week-old male Osborne-Mendel rats fed diets containing 50 or 100 ppm Mg developed transitory priapism and hyperemia, signs of Mg deficiency. Based on a treadmill test, these rats showed a markedly lower exercise endurance capacity (four hours) than rats fed the higher levels of dietary Mg (six hours). They also showed a mild macrocytic anemia. Consumption of a mineral water containing 85 ppm Mg prevented these signs of Mg deficiency. These results show that a reduction in exercise capacity can be an early effect of Mg deficiency. Hematologic changes that occurred with Mg deficiency such as macrocytic anemia may be responsible, at least in part, for the depression of exercise observed in these rats. These data are important because they illustrate the potential significance of even a marginal deprivation of dietary magnesium.

Animals↗

Sickle cell disease in Sudan.

The clinical, haematological and biochemical features of 50 Sudanese patients with sickle cell disease (SCD) were determined. Of 23 patients with complete family data, 21 had sickle cell anaemia (homozygous HbSS), 2 had sickle-cell/beta+thalassaemia but none had sickle cell/beta Othalassaemia. The remaining 27 patients had HbSS phenotype. 84% of patients were from the Baggara tribe in western Sudan, where HbS is a natural extension of the west African HbS belt. 21 patients were children under 2 years old; 19 were 3-10 years old; and the remaining 10 were over 10 years old. Young patients presented mainly with painful vaso-occlusive crisis, severe anaemia, hand and foot syndrome, fever, underweight, malnutrition and various infectious diseases. All patients had mild to moderate cardiac enlargment; 42% had a moderately enlarged spleen but only 10% had an enlarged liver; 20% had infarctive lesions of long bones and another 8% had Salmonella osteomyelitis. Leg ulcers, priapism, enuresis and cholelithiasis were not observed. Patients had a mean haemoglobin concentration of 7.3 g/dl; reticulocyte count of 15.1%; serum bilirubin of 2.1 mg/dl; HbA2 level of 2.8% and HbF of 7%. Thus, the observed pattern of SCD in Sudan is comparable to the severe type described for Africans and not comparable to the benign form found in Shiite Moslem Arabs of Saudi Arabia. 6 adults with mild SCD had HbF levels below 5%. Amelioration of the disease, therefore, does not seem to be related to HbF levels; nor was it possible to relate it to high levels of erythrocyte 2,3-diphosphoglycerate.

2,3-Diphosphoglycerate↗

Issues in management of scorpion sting in children.

All children admitted to Madina Maternity and Children's Hospital, Saudi Arabia, in 1989 because of scorpion stings (primarily Leiurus quinquestriatus) were studied. Of 96 children studied, 20 suffered either shock, pulmonary oedema or both. These 20 shared characteristic clinical features such as vomiting, priapism and failure to maintain normal temperature and/or blood pressure. The management protocol emphasized fluid restriction and the i.v. administration of venom antitoxin. Doubling the recommended dose did not improve the outcome. Two children died and the rest recovered.

Adolescent↗

Corpus cavernography prior to insertion of penile prostheses.

Our experience with corpus cavernography prior to the insertion of a penile prosthesis is presented. We suggest that this investigative procedure should be used as a routine to determine the patency of the "corporal tubes," particularly in patients in whom corporal fibrosis is a possibility, such as a previous episode of priapism.

Adult↗

Systemic complication of intracavernous papaverine injection in patients with venous leakage.

Intracavernous papaverine injection is often used in the diagnosis and treatment of male impotence. Prolonged erection and/or priapism are well known local complications. Systemic side-effects characterized by discomfort and dizziness due to rapid escape of the drug into the vascular circulation also can occur in patients with venous leakage. Thus, venous leakage should be ruled out prior to intracavernous injection of papaverine in the treatment of impotence. Ligation of the deep dorsal vein and the small veins around the tunica albuginea will lessen the problem.

Erectile Dysfunction↗

Intracavernous injections of papaverine and phentolamine: correlation with penile brachial index.

Eighty-two patients were evaluated for erectile failure with a comprehensive history, physical examination, hormonal testing, noninvasive Doppler examination (PBI), and nocturnal penile tumescence (NPT). After these studies all patients received intracavernous injection with a combination of papaverine (50 mg) and phentolamine (1.66 mg), and both tumescence and rigidity were monitored. Rigidity response was compared with the PBI. The number of patients with a poor rigidity response in each PBI category were: 3 of 5 with a PBI of less than 0.6 (vasculogenic), 7 of 11 with a PBI of 0.6-0.75 (ambiguous), and 25 of 66 with a PBI of 0.75-1.0 (normal). These results indicate only a marginally significant association between PBI and intracavernous injection. The procedure was safe with no long-term sequelae from injection observed, and no surgical intervention was required. Complications of injections included reversible priapism in 11 patients (13.4%), transient dizziness in 10 patients (12.2%), and hematoma in 5 patients (6.2%). This study suggests that intracavernous injection with a drug combination may be a more sensitive screening test for vasculogenic impotence than noninvasive Doppler studies because it more closely simulates the erectile response.

Adult↗

Renal cell carcinoma involving penis and testis: unusual initial presentations of metastatic disease.

Solitary parenchymal metastases of renal cell carcinoma to the penis or testis are rare. We report 1 case of each: in one instance the patient presented with priapism and an asymptomatic primary tumor; in the other, the metastasis presented as an acute change in a long-standing hydrocele more than one year after nephrectomy. Both patients had either positive margins at resection or recurrence after resection of the metastasis. While long-term, disease-free survival has been reported after orchiectomy for isolated metastatic disease, penile involvement appears to carry a very poor prognosis.

Aged↗

Fixed drug eruption to papaverine.

Papaverine has offered new options for therapy in erectile dysfunction. Various complications have been reported with papaverine, the prominent ones being priapism and liver function abnormalities. We present a previously unreported case of a fixed drug eruption caused by papaverine.

Drug Eruptions↗

Comparison of homozygous sickle cell disease in northern Greece and Jamaica.

The clinical and haematological features of homozygous sickle cell (SS) disease were compared in 30 Greek and 310 Jamacian patients. Deletional alpha-thalassaemia, which modifies SS disease, is rare among Greek patients, so only Jamacian patients with four alpha-globin genes were included in the control group. Greek patients had higher total haemoglobin concentration and red cell counts, and lower mean cell haemoglobin concentration (MCHC) and reticulocyte counts. They also had a more normal body build and more adults had persistent splenomegaly. Fewer had a history of leg ulceration or priapism but more reported acute chest syndrome. The comparatively mild disease in Greek patients is consistent with less haemolysis and sickling and therefore less bone marrow expansion. In the absence of amelioriating factors such as high HbF concentration or alpha-thalassaemia, these findings may be explained by the low MCHC.

Adolescent↗

Large-vessel occlusion in sickle cell disease: pathogenesis, clinical consequences, and therapeutic implications.

Much of the morbidity and mortality in sickle cell disease (SCD) is caused by tissue ischemia and infarction resulting from vascular occlusion. Research in this area has been dominated by the hypothesis that vascular occlusion in SCD is due primarily to microvascular obstruction by sickle erythrocytes (SS RBC), yet there is no direct evidence that microvascular occlusion is responsible for any of the vasocclusive complications of SCD. In this paper an alternate hypothesis is proposed: that thrombotic occlusion of larger arteries and veins is an important factor in many of the vasocclusive complications of SCD. Large-vessel cerebral arterial disease (intimal hyperplasia with superimposed thrombosis) has clearly been established as the most important cause of stroke in SCD, and considerable evidence suggests that pulmonary arterial thrombosis/embolism is a major cause of pulmonary infarction and hypertension. The involvement of large-vessel thrombosis in painful crisis, aseptic necrosis of bone, priapism, leg ulcers, retinopathy, and miscarriage has not been adequately investigated. Large-vessel occlusion in SCD is probably a consequence of the abnormal adhesive and procoagulant properties of SS RBC, which produce endothelial damage, secondary intimal proliferation, and thrombosis. Techniques currently used to treat large-vessel occlusion in other disorders (antiplatelet and anticoagulant agents, thrombolytic therapy, angioplasty, endarterectomy, and vascular bypass surgery) should be considered in sickle cell subjects with large-vessel occlusion, especially in the cerebral vasculature.

Anemia, Sickle Cell↗

Emergencies caused by side effects of psychiatric medications.

Psychiatric medications cause side effects in several organ systems that need emergency evaluation and treatment. Serious cardiovascular side effects include postural hypotension, cardiac conduction blockade, and SA mode dysfunction; serious neurological side effects include extrapyramidal reactions, seizures, delirium, catatonia, pseudotumor cerebri, ataxia, and glaucoma; serious genitourinary side effects include urinary retention, nephrotic syndrome, and priapism, and the serious hematological side effect of agranulocytosis. Also potentially fatal syndromes secondary to psychiatric drugs are the neuroleptic malignant syndrome, hyperandrenergic crisis, the serotonin syndrome, and lithium toxicity. Individual psychiatric drug classes most notorious for causing side effects with high morbidity and mortality are low potency neuroleptics, clozapine, tertiary tricyclics, monoamine oxidase inhibitors, and lithium.

Agranulocytosis↗

Delayed traumatic spinal epidural hematoma with spontaneous resolution of symptoms.

Post-traumatic spinal epidural hematomas are uncommon, usually requiring emergent neurosurgical evacuation. We present a symptomatic delayed post-traumatic epidural hematoma of the T-spine that resolved within hours of administration of high dose steroids. A 22-year-old man presented 10 days after sustaining blunt trauma during a motor vehicle crash. He developed signs of acute cord compression with loss of sensation and motor function in bilateral lower extremities with priapism. Magnetic resonance imaging demonstrated a spinal epidural hematoma with 50% canal stenosis at the T4 level. His symptoms improved 1 h after the administration of high dose steroids. All symptoms resolved completely while the patient was in the Emergency Department and he was treated conservatively by Neurosurgery with no further sequelae. Thoracic spinal epidural hematoma is an uncommon condition that may present in delayed fashion after trauma with significant neurologic compromise. If neurologic symptoms improve with initial steroid therapy, patients with this condition may be treated conservatively with steroids and observation.

Adult↗

Plasma levels of plasminogen activator inhibitor type 1, factor VIII, prothrombin activation fragment 1+2, anticardiolipin, and antiprothrombin antibodies are risk factors for thrombosis in hemodialysis patients.

Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non-systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition, there was a reduction of factor XII during the treatment. It is possible to assume in the TC group and, to a lesser extent, also in the NTC group that endothelial cells liberate PAI-1 in the vascular lumen, which causes hypofibrinolysis. In addition, an excess of factor VIII is activated by endothelial dysfunction with subsequent activation of the coagulation cascade as shown by increased F1+2 and fibrinogen. ACA-IgM, in turn, is capable of interfering with the system of protein C, a potent anticoagulant factor that inactivates cofactors Va and VIIIa. They also induce the expression of procoagulant factors on the surface of the endothelial cells. In conclusion, the hypercoagulable state caused by alterations of coagulation and fibrinolytic factors is a cause of vascular access dysfunction and thrombosis of other vessels.

Antibodies↗

Overall cardiovascular profile of sildenafil citrate.

Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is the first in a new class of orally effective treatments for erectile dysfunction. During sexual stimulation, the cavernous nerves release nitric oxide (NO), which induces cyclic guanosine monophosphate (cGMP) formation and smooth muscle relaxation in the corpus cavernosum. Sildenafil facilitates the erectile process during sexual stimulation by inhibiting PDE5 and thus blocking the breakdown of cGMP. Sildenafil alone can cause mean peak reductions in systolic/diastolic blood pressure of 10/7 mm Hg that are not dose related, whereas the heart rate is unchanged. Sildenafil and nitrates both increase cGMP levels in the systemic circulation but at different points along the NO-cGMP pathway. The combination is contraindicated because they synergistically potentiate vasodilation and may cause excessive reductions in blood pressure. Erectile dysfunction is a significant medical condition that shares numerous risk factors with ischemic heart disease, and hence a substantial overlap exists between these patient groups. From extensive clinical trials, the most commonly reported cardiovascular adverse events in patients treated with sildenafil were headache (16%), flushing (10%), and dizziness (2%). The incidences of hypotension, orthostatic hypotension, and syncope and the rate of discontinuation of treatment due to adverse events were <2% and were the same in patients taking sildenafil and those taking placebo. Retrospective analysis of the concomitant use of antihypertensive medications (beta blockers, alpha blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium antagonists) in patients taking sildenafil did not indicate an increase in the reports of adverse events or significant episodes of hypotension compared with patients treated with sildenafil alone. In clinical trials, the incidence of serious cardiovascular adverse events, including stroke and myocardial infarction, was the same for patients treated with sildenafil or placebo. Concurrent disease states, such as renal or hepatic impairment, or concomitant use of inhibitors of the cytochrome P450 isozyme CYP3A4 could increase systemic exposure to sildenafil. Since the US market launch in April 1998, monitoring of spontaneous adverse event reports in association with sildenafil has demonstrated a pattern that is generally consistent with the experience observed during clinical development, with the exception of infrequent reports of priapism. In conclusion, extensive clinical testing has shown that overall treatment with sildenafil for up to 1 year is well tolerated and is associated with a low incidence of adverse events that result in discontinuation of treatment in <3% of patients.

3',5'-Cyclic-GMP Phosphodiesterases↗

Airbags and children: a spectrum of C-spine injuries.

Over 30 children who were improperly restrained or in rear facing safety seats have been reported killed in motor vehicle accidents (MVA) involving airbags. The authors report one minor and two major injuries in properly restrained children in the front passenger seat. In case 1, A 10-year-old seat-belted boy was involved in an MVA (40 km/h) with deployment of both airbags. Physical examination findings showed right hyphema with corneal abrasion, right cheek abrasion and minimal cervical tenderness. C-spine x-ray was normal. He was treated for whiplash and facial burns resulting from contact with hot gas released by the airbags and discharged. In case 2, a 4-year-old boy wearing a lapbelt was in a MVA (20 km/h) with airbag deployment. On arrival, his Glasgow coma score was 3 and he was hemodynamically unstable. Secondary survey after stabilization showed left neck abrasions and ecchymoses, quadraplegia, priapism, and absent rectal tone. C-spine x-ray showed atlanto-occipital dislocation with possible complete spinal cord transection at C1. Aggressive maneuvers were withheld, and the patient was pronounced dead. Autopsy findings confirmed the clinical diagnosis. In case 3, a 3-year-old boy in a forward-facing safety seat was in a MVA (60 km/h) with air bag deployment. The patient was fully awake. C-spine x-rays were normal. Because of fluctuating level of consciousness, he underwent head computed tomography (CT) scan, which demonstrated a posterior fossa subarachnoid hemorrhage and a hematoma posterior to the odontoid, suggesting a ligamentous tear. He remained asymptomatic and was discharged on day 6. A head CT scan at 1 month showed a periosteal reaction in the area of the alar ligament suggestive of partial ligamentous avulsion; this injury was the forerunner of atlanto-occipital dislocation. Airbags deploy by releasing a hot effluent at 300 km/h. Mechanisms of injury include direct contact of hot gas with facial skin and energy transmitted directly from the airbag system to the child's head and neck. These cases illustrate a spectrum of C-spine injuries caused by airbag deployment and support the recommendation that children under 12 years of age travelling in a car equipped with dual airbags be seated in the back.

Accidents, Traffic↗

Treatment of intracorporeal injection nonresponse with sildenafil alone or in combination with triple agent intracorporeal injection therapy.

PURPOSE: We assess the efficacy of sildenafil as salvage therapy for intracorporeal injection therapy nonresponse. MATERIALS AND METHODS: The study group comprised 93 patients with a mean age of 53.6 years (range 24 to 77) with chronic erectile dysfunction. In all cases a home trial of intracavernosal injection of high dose alprostadil and triple agent intracavernosal injection therapy had failed. Patients were treated with sildenafil citrate alone or in combination with intracavernosal injection therapy. RESULTS: The etiology of erectile dysfunction was arteriogenic in 29 cases, cavernosal venous leakage in 36, mixed vasculogenic in 24, psychogenic in 3 and post-priapism intracavernous fibrosis in 1. Of the 32 sildenafil responders (34% of the study group) 30 required 100 and 2 required 50 mg. The 29 sildenafil intracavernosal injection (combined therapy) responders (31% of the study group) required 100 mg. sildenafil. There were 32 nonresponders (34% of the study group). Mean International Index of Erectile Function questions 3 and 4 scores were 1.7 and 1.5 at baseline, 2.3 and 1.9 with intracavernosal injection, 4.6 and 42.2 with sildenafil, and 4.1 and 4.10 with combined therapy, respectively. Of the 93 patients 29 (31%) treated with intracavernosal injection reported adverse effects, including penile pain in 27, dizziness in 5 and headache in 2. Of the patients treated with sildenafil 34 (37%) reported side effects, including headache in 30, facial flushing in 25, dyspepsia in 12, nasal congestion in 9, dizziness in 5 and visual disturbances in 1. Of the 41 patients given combined therapy 20 (49%) reported adverse effects, including penile pain in 15, headache in 15, facial flushing in 12, dyspepsia in 7, nasal congestion in 3, dizziness in 12 and syncope in 1. CONCLUSIONS: Sildenafil alone or sildenafil plus intracavernosal injection is effective salvage therapy for intracavernosal injection nonresponse. Sildenafil in combination with intracavernosal injection is associated with a 33% incidence of adverse effects, including a 20% incidence of dizziness.

Adult↗

Pharmacokinetics of vasoactive substances administered into the human corpus cavernosum.

The pharmacokinetics of vasoactive substances injected into the corpus cavernosum for the treatment of erectile dysfunction have not been investigated to date. We measured the local intracavernous and peripheral venous concentration curves of papaverine and prostaglandin E1, and its primary metabolite 15-keto-13,14-dihydro-prostaglandin E1 in an intra-individual comparison after intracavernous injection. Papaverine was measured with high performance liquid chromatography and prostaglandin E1 was measured with a specially adapted radioimmunoassay. The results demonstrate that papaverine is slowly draining into the systemic circulation, showing slightly elevated levels in the peripheral blood 30 and 60 minutes after injection. Prostaglandin E1 shows a much faster decrease in local concentrations with no measurable increase in the periphery, probably due to the short half-time after lung passage. Measurement of the primary metabolite proves a local degradation of prostaglandin E1 in the corpus cavernosum into the biologically inactive 15-keto-13,14-dihydro-prostaglandin E1, which also shows a slight increase in the peripheral circulation due to the longer half-time of approximately 8 minutes. The data provide good explanation for the clinical finding of a markedly decreased incidence of priapism with the use of prostaglandin E1, which can be shown to be locally metabolized, compared to papaverine, which is retained in the corpus cavernosum in cases of nonvenogenic impotence.

Alprostadil↗