Conformational change in bacterio-opsin on binding to retinal.

The detailed mechanism of retinal binding to bacterio-opsin is important to understanding retinal pigment formation as well as to the process of membrane protein folding. We have measured the temperature dependence of bacteriorhodopsin formation from bacterio-opsin and all-trans retinal. An Arrhenius plot of the apparent second-order rate constants gives an activation energy of 11.6 +/- 0.7 kcal/mol and an activation entropy of -4 +/- 2 cal/mol deg. Comparison of the activation entropy to model compound reactions suggests that chromophore formation in bacteriorhodopsin involves a substantial protein conformational change. Cleavage of the polypeptide chain between residues 71 and 72 has little effect on the activation energy or entropy, indicating that the connecting loop between helices B and C is not involved in this conformational change.

Actinomocosis toracoabdominal / Thoracic and abdominal actinomycosis

Presentamos una paciente de 30 años de edad que padecía una actinomicosis toracoabdominal. Se realizaron Rx simple de tórax, ecografía abdóminopelviana y de partes blandas y cortes tomográfico toracoabdominales según protocolos estandarizados, comprobando un importante compromiso locorregional invasor de la enfermedad y confirmando el diagnóstico por anatomía patológica (AU)

Actinomocosis toracoabdominal / Thoracic and abdominal actinomycosis

Presentamos una paciente de 30 años de edad que padecía una actinomicosis toracoabdominal. Se realizaron Rx simple de tórax, ecografía abdóminopelviana y de partes blandas y cortes tomográfico toracoabdominales según protocolos estandarizados, comprobando un importante compromiso locorregional invasor de la enfermedad y confirmando el diagnóstico por anatomía patológica

Thrombosis resulting from heparin therapy.

Heparin is widely used in current practice for a variety of indications. It is well known that it can cause thrombocytopenia, but not that thrombosis may also develop in thrombocytopenic patients and cause significant morbidity and mortality. A 56-year-old woman developed heparin-induced thrombocytopenia with thrombosis that resulted in the amputation of her leg. It is proposed that the reaction has an immune-mediated mechanism. Several ways of diagnosing the condition are available, specifically the serotonin-release assay and an enzyme-linked immunosorbent assay. The investigational agent danaproid may be effective in the treatment of heparin-induced thrombocytopenia with thrombosis.

Pharmacologic management of adult idiopathic nephrotic syndrome.

The pathophysiology, clinical features, complications, and pharmacologic management of adult idiopathic nephrotic syndrome are reviewed. Loss of plasma proteins in the urine is the primary process leading to the nephrotic syndrome, which is characterized by hypoalbuminemia, hyperlipidemia, and edema. The four principal causes, or subclasses, of adult idiopathic nephrotic syndrome are membranous nephropathy (MN), minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranoproliferative glomerulonephritis (MPGN); definitive diagnosis requires histologic examination of a renal biopsy specimen. Treatment of nephrotic syndrome may be directed at the specific cause of the proteinuria, the proteinuria itself, or the complications induced by the syndrome. The four subclasses of nephrotic syndrome vary in their response to therapy. Corticosteroids, alone or in combination with cytotoxic agents, and cyclosporine have been used to induce partial or complete remission in patients with MN, MCD, and FSGS; combinations of corticosteroids, cytotoxic agents, platelet inhibitors, and anticoagulants have been used to treat patients with MPGN. Treatment of proteinuria involves dietary protein restriction with the possible addition of an angiotensin-converting-enzyme inhibitor or a nonsteroidal anti-inflammatory drug. Management of the complications of nephrotic syndrome encompasses the use of diuretics; a low-cholesterol, low-fat diet; lipid-lowering agents; and anticoagulants. Patients with nephrotic syndrome are in a constant state of flux with respect to fluid status, organ function, and critical protein balance. Treatment is based on the histologic subclass of the disease.

The use of norfloxacin in a university hospital.

Because of increasing norfloxacin use and the development of resistant organisms, an evaluation was undertaken in a University Hospital to assess the appropriateness of norfloxacin for the treatment of urinary tract infections and to calculate the potential cost savings associated with more cost-effective antibiotic therapy. Medical records of 64 patients receiving norfloxacin for a 31-day period were concurrently reviewed. Of these, 58 patients were treated for urinary tract infections and four patients received urinary tract infection prophylaxis. Fourteen patients were prescribed solely empiric therapy whereas an additional 44 patients received definitive treatment confirmed by culture results. Based on the predetermined criteria, norfloxacin use for the definitive treatment of urinary tract infections was deemed to be appropriate in 34 of the 44 patients. Three additional courses of therapy were also judged to be appropriate due to documented signs and symptoms associated with urinary tract infections, despite cultures with less than 10(5) colony forming units per mL urine. Reasons for inappropriate use in the remaining seven patients included isolation of fewer bacteria than required by the criteria in asymptomatic patients (3 cases), isolation of organisms not sensitive to norfloxacin (1 case) and lack of dosage adjustment for renal insufficiency (3 cases). Nineteen of 32 evaluable inpatients (59%) received norfloxacin when a less expensive, equally effective agent was available. Although savings from more cost-effective therapy of urinary tract infections are minimal, due to the potential emergence of resistant organisms, norfloxacin should be reserved for infections not amenable to treatment with other oral antibiotics.

Appropriate but not cost effective ceftazidime use in a university hospital.

An evaluation of ceftazidime use at a university hospital was performed. Drug utilization evaluations usually categorize therapies as appropriate or inappropriate, with the inappropriate category including all regimens which are not cost effective. This may be misleading since therapy which is therapeutically appropriate may be labeled as inappropriate. Therefore, ceftazidime use was classified as appropriate, appropriate but not cost effective, or inappropriate. Clinical pharmacists reviewed the charts of 72 patients over a 1 month period. Courses of therapy were first categorized as empiric or definitive and as appropriate or inappropriate. Those that were appropriate were further analyzed to determine cost effectiveness. When a more cost effective regimen was available, the difference in cost was calculated; the cost of inappropriate therapy was compared to that of an appropriate alternative regimen. Ceftazidime use was appropriate and cost effective in 22% of courses, appropriate but not cost effective in 66%, and inappropriate in 11%. Annual savings of up to $72,000 could be realized in our 550 bed hospital by intervention into appropriate but not cost effective therapy and inappropriate therapy.

Management of cirrhotic ascites.

The pathogenesis and diagnosis of cirrhotic ascites are reviewed, and the treatment options are described, focusing on pharmacologic management. The major theories on the pathogenesis of cirrhotic ascites are the underfill and overflow theories. The underfill theory states that ascites formation results in decreased plasma volume leading to renal sodium and water retention. The overflow theory states that the initial event in ascites formation is renal sodium retention. Evidence suggests that the formation of ascites is a continuum involving both overflow (early) and underfill (late) mechanisms. Although the most frequent cause of ascites is hepatic cirrhosis, analysis of the ascitic fluid is important to exclude other causes (e.g., neoplasm, peritonitis, pancreatitis). Patients who do not respond to treatment with sodium restriction and bed rest require diuretic therapy. Spironolactone is the agent of choice for treatment of the nonazotemic patient with cirrhotic ascites. Combination therapy with spironolactone and furosemide or spironolactone and metolazone may be used in those patients who do not respond to spironolactone. Patients with impaired renal function should not be treated with spironolactone because of the risk of hyperkalemia. Paracentesis with albumin replacement has been used successfully for treatment of patients with tense cirrhotic ascites. Initial management of cirrhotic ascites is conservative, with sodium restriction and bed rest. Spironolactone is a good first-choice drug for treatment of ascites. Daily weight, serum electrolytes, and renal function should be monitored to assess the effectiveness and potential adverse effects of diuretic therapy.