Whipple's disease: pathogenetic considerations

A typical case of Whipple's disease was manifested by malabsorption and nondeforming peripheral arthritis for five years. A definite diagnosis was made by duodenal mucosal biopsy which revealed the characteristic histologic features by light microscopy, intracellular and extracellular Whipple's bacilli by electron microscopy, and a typical immune cross-reactivity pattern by immunofluorescence technique. Whipple's bacilli apparently elicit no effective humoral and cellular immune response; macrophages thus play the key role in its pathogenesis. Antibiotic treatment resulted in a dramatic relief of symptoms and rapid restoration of body weight. We stress that in patients with nondeforming peripheral arthritis associated with malabsorption syndrome, Whipple's disease, despite its rarity, should be included in the differential diagnosis.     

Diagnostic and pathogenetic considerations in transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is an infrequent but life- threatening complication of hemotherapy. The findings in 36 cases are described. The typical clinical presentation includes acute respiratory distress characterized by hypoxemia and fulminant pulmonary edema. The onset is usually within 4 hours of transfusion and is accompanied by hypotension. In most patients (81%), recovery is rapid and complete. In 89 percent of cases, granulocyte or lymphocytotoxic antibodies are found in the serum of the implicated blood product which contained plasma. HLA-specific antibodies were identified in donor serums in 65 percent of cases evaluated. The passive transfer of these antibodies may promote complement activation and subsequent pulmonary injury. TRALI is an important cause of transfusion-associated morbidity and is probably often misdiagnosed. Blood banks need to identify donors whose plasma causes these reactions in order to prevent their recurrence.     

Pittsburgh Epidemiology of Diabetes Complications Study. Measuring diabetic neuropathy follow-up study results.

OBJECTIVE--This project evaluated the utility of quantitative sensory techniques in predicting the development of neuropathy for subjects participating in a prospective study. RESEARCH DESIGN AND METHODS--Distal symmetric polyneuropathy was evaluated in 77 insulin-dependent diabetes mellitus individuals via quantitative sensory testing, nerve conduction studies, and clinical examination. RESULTS--Although the specificity and positive predictive value were low for the quantitative sensory techniques as predictors of neuropathy diagnosed on clinical exam approximately 2 yr later, the sensitivity for vibratory thresholds was high (100%). Variability over the 2-yr interval was shown on follow-up testing for each of the objective assessment modalities and it was not explained by differences for potential risk factors measured at baseline. CONCLUSION--Despite a cross-sectional relationship between the assessment modalities and clinically overt neuropathy at baseline, these follow-up data suggest that the potential for the objective modalities as predictors of clinically diagnosed neuropathy may be limited.     

Pseudohyperaldosteronism: pathogenetic mechanisms

Pseudohyperaldosteronism is characterized by a clinical picture of hyperaldosteronism with suppression of plasma renin activity and aldosterone. Pseudohyperaldosteronism can be due to a direct mineralocorticoid effect, as with desoxycorticosterone, fluorohydrocortisone, fluoroprednisolone, estrogens, and the ingestion of high amounts of glycyrrhetinic acid. A block of 11-hydroxysteroid-dehydrogenase type 2 (11HSD2), the enzyme that converts cortisol into cortisone, at the level of epithelial target tissues of aldosterone, is involved in other cases. This mechanism is related either to a mutation of the gene, which encodes 11HSD2 (apparent mineralocorticoid excess syndrome and some cases of low renin hypertension) or to an acquired reduction of the activity of the enzyme due to glycyrrhetinic acid, carbenoxolone, and grapefruit juice. In other cases saturation of 11HSD2 may be involved as in severe Cushing's syndrome and chronic therapy with some corticosteroids. Recently, an activating mutation of the mineralocorticoid receptor gene has been described. Another genetic cause of pseudohyperaldosteronism is the syndrome of Liddle, which is due to a mutation of the gene encoding for beta and gamma subunits of the sodium channels.     

Secondary analysis: theoretical, methodological, and practical considerations.

Secondary analysis, which involves the use of existing data sets to answer new research questions, is an increasingly popular methodological choice among researchers who wish to investigate particular research questions but lack the resources to undertake primary data collections. Much time loss and considerable frustration may result, however, if researchers begin secondary analyses without an awareness of the distinctive methodological and practical challenges involved. This article highlights difficulties that may arise when researchers use data from previous clinical research projects, including theoretical issues and problems involving sampling, measurement, and external and ecological validity. It also offers practical suggestions for undertaking a secondary analysis and criteria for evaluating secondary analyses.     

Vulvovaginal conditions: social, psychological, and sexual considerations.

Women experiencing vulvovaginal conditions are affected socially, psychologically, and sexually. Although vulvovaginitis is a common women's health problem, these considerations are overlooked in the literature and, unfortunately, often in practice, as well. This article presents a discussion of the social, psychological, and sexual issues to be considered when treating women with vulvovaginal conditions, including implications for practice.     

Cardiorenal syndromes: pathogenetic, clinico-diagnostic, prognostic and therapeutic aspects

Current information on cardiorenal and renocardial relations with clinicopathophysiological disorders in which primary impairment of the heart or kidneys leads to secondary functional and morphological abnormality in the other organ is analysed. Acute decompensation of cardiac failure is wide spread pathology which can be complicated by both acute and chronic lesion of the kidneys. Acute renal failure in cardiogenic shock in patients with ST elevation acute myocardial infarction deteriorates prognosis and raises lethality. Administration of radiopharmaceutical in patients with myocardial infarction and coronary heart disease with stents may induce nephropathy. Synergic affection of the heart and kidneys is observed in diabetes mellitus, systemic lupus erythematosus, amyloidosis, infectious endocarditis and some other diseases.     

Complications arising after thoracic aortic surgery: A case report on an unusual spinal cord infarction. Physiopathological and clinical considerations

Even though new prevention techniques have been developed and are being used during thoraco-abdominal aortic repairs, spinal cord infarction remains a severe and relatively frequent complication of aortic surgery. Infarctions in the territory of the anterior spinal artery are considered the most common. Different clinical pictures related to spinal cord transverse extension wounds are drawn up. In this paper, we present a case report of a subject having presented an isolated motor deficit of the lower limbs and a favorable prognosis, suggesting selective involvement of the anterior horns of the spinal cord subsequent to surgical repair of an aortic dissection. We wish to review the relevant anatomical, clinical and diagnostic characteristics along with current techniques of spinal cord ischemia prevention during and after surgery.     

Molecular pathogenetic mechanisms of nephrotic edema: progress in understanding.

Molecular and pathogenetic mechanisms in sodium retention and water reabsorption of nephrotic edema are discussed. Are reported and analyzed molecular mechanisms about sodium retention in collecting duct cells regarding activation and surface expression of epithelial sodium channels (ENaC) and sodium-potassium-ATPase (Na,K-ATPase) by aldosterone, vasopressin, natriuretic peptide system (underfill theory): is necessary a better understanding about the dysregulation of ENaC and Na,K-ATPase surface expression and the resistance to natriuretic peptide system. Are also reported and analyzed molecular mechanisms of sodium retention in proximal tubule cells regarding intrinsic albumin toxicity upon type 3 sodium-hydrogen exchanger ionic pump and the activity of sodium-hydrogen exchanger regulatory factor protein (overfill theory): a better knowledge about the link between albumin, sodium-hydrogen exchanger type 3 (NHE3) ionic pump, sodium-hydrogen exchanger regulatory factor protein is necessary. Then molecular mechanisms of vasopressin free water retention through acquaporin water channels in collecting duct cells are discussed: further studies are necessary to understand vasopressin release pathway (osmotic/nonosmotic) and V2 receptor activation with cell surface expression of renal acquaporins water channel.     

Gastric, intestinal, and gallbladder varices: hemodynamic and therapeutic considerations.

Atypically located varices are frequently overlooked in the differential diagnosis of gastrointestinal bleeding in patients with portal hypertension. The circulatory changes associated with these lesions are described and their relation to diagnosis and treatment emphasized.     

Cardiogenic ischemic strokes: pathogenetic aspects

Eighty-three patients with acute ischemic stroke (56 men and 27 women, mean age 90.1 +/- 10.8 years) were examined in order to elucidate the significance of paroxysmal heart rhythm disorders and silent myocardial ischemia and determine the pattern of hemorheological changes. Traditional clinical instrumental examinations were supplemented by Holter monitoring and measurements of a wide spectrum of hemostatic and hemorheological values. Cardiogenic ischemic strokes were pathogenetically heterogeneous. Holter monitoring helped detect the significance of paroxysmal atrial fibrillation in the pathogenesis of embolic cardiogenic stroke. One of the key factors in development of hemodynamic cardiogenic stroke was transitory bradyarrhythmia and deterioration of left-ventricular contractility. Cardiogenic strokes are associated with hemostatic activation with predominant changes in the plasma hemostasis, which dictates purposeful hemocorrection.     

Double-blind, placebo-controlled homeopathic pathogenetic trials: symptom collection and analysis

BACKGROUND: Homeopathic pathogenetic trials (provings) are fundamental to homeopathy. Since most of the data from available provings have not been statistically evaluated, it is unclear how specific reported symptoms are and how they differ from those reported by people taking placebo. METHOD: We combine and analyse data from two different homeopathic pathogenic trials--including 10 and 11 provers, respectively, and both including 30% placebo-to test the null hypothesis that there is no significant difference between the number of symptoms in placebo and verum groups. RESULTS: The principal results were: Placebo reported less symptoms than verum groups. Symptom distribution according to predefined classes (common symptoms increased in intensity and/or duration-, cured, old, new and exceptional) was statistically different between placebo and verum group at a high level of significance (P<0.001). Compared to verum, placebo provers reported less new and old but more common (increased in duration or intensity) symptoms. Within repertory categories, other differences were detected. The two groups differ in terms of the duration of each symptom and kinetics of symptoms: most symptoms were more persistent in verum than in placebo groups and verum provers recorded a decreasing number of symptoms with time. Placebo provers did not show such a temporal pattern. CONCLUSIONS: If confirmed by other studies these results would demonstrate the non-equivalence between homeopathic medicines in high dilution and placebo and contribute to the improvement of proving methodology and evaluation.     

Heart transplantation in children: indications, complications, and management considerations.

Heart transplantation in children has increased in the last 5 years because of the availability of cyclosporine and improved surgical techniques. The primary indications for transplantation in children are dilated cardiomyopathy and complex congenital heart disease. The major complications affecting morbidity and mortality are infection and rejection. However, the development of accelerated coronary artery disease represents a serious complication limiting long-term survival. Successful rehabilitation and long-term survival depend on careful selection of potential recipients, application of stringent medical and psychosocial criteria, operative technique, comprehensive medical surveillance, and thorough and effective patient and family education.     

Oxcarbazepine in painful diabetic neuropathy: a randomized, placebo-controlled study.

In this multicentre, placebo-controlled, 16-week trial, the efficacy and safety of oxcarbazepine monotherapy in patients with neuropathic pain of diabetic origin was evaluated. Eligible patients had a 6-month to 5-year history of neuropathic pain symptoms of diabetic origin and a pain rating of > or =50 units on the visual analogue scale (VAS). Oxcarbazepine was initiated at a dose of 300 mg/day and titrated to a maximum dose of 1800 mg/day. In total, 146 patients (oxcarbazepine, n=69; placebo, n=77) were randomized. After 16 weeks, oxcarbazepine-treated patients experienced a significantly larger decrease in the average change in VAS score from baseline compared with placebo (-24.3 vs. -14.7 units, respectively; p=0.01). The reduction from baseline in mean VAS score for oxcarbazepine-treated patients was of a greater magnitude than placebo as early as week 2 (-8.0 vs. -4.7; p<0.05). A significantly greater proportion of oxcarbazepine-treated patients experienced a >50% reduction from baseline in VAS score at the end of treatment compared with placebo (35.2% vs. 18.4%, respectively; p=0.0156; number needed to treat=6.0). Global assessment of therapeutic effect rating was improved in more oxcarbazepine patients than placebo patients (48% vs. 22%, respectively; p=0.0025). Patients on oxcarbazepine were awakened less frequently due to pain than patients on placebo. Most adverse events were mild to moderate in severity, transient, and in line with the known tolerability profile of oxcarbazepine. These observations suggest that oxcarbazepine monotherapy, pending additional trials, may be efficacious and may provide clinically meaningful pain relief in patients with neuropathic pain of diabetic origin.