Acute generalized exanthematous pustulosis induced by metronidazole: the role of patch testing

Perineal rectosigmoidectomy with a hand-sewn anastomosis is thought to be the most appropriate procedure for elderly patients deemed unfit to tolerate a major abdominal operation. However, the use of a circular stapling device to perform the coloanal anastomosis following rectosigmoidectomy shortens the operative time and provides a more secure anastomosis than the traditional hand-sewn technique.     

Acute generalized exanthematic pustulosis: a case with a lymphoma-like presentation

A 28-year-old woman developed an acute generalized exanthematic pustulosis in association with a massive lymphadenopathy. A viral etiology seemed highly probable although a drug reaction could not be excluded.     

Resistance to HIV protease inhibitors: a comparison of enzyme inhibition and antiviral potency

Resistance of HIV-1 to protease inhibitors has been associated with changes at residues Val82 and Ile84 of HIV-1 protease (HIV PR). Using both an enzyme assay with a peptide substrate and a cell-based infectivity assay, we examined the correlation between the inhibition constants for enzyme activity (Ki values) and viral replication (IC90 values) for 5 active site mutants and 19 protease inhibitors. Four of the five mutations studied (V82F, V82A, I84V, and V82F/I84V) had been identified as conferring resistance during in vitro selection using a protease inhibitor. The mutant protease genes were expressed in Escherichia coli for preparation of enzyme, and inserted into the HXB2 strain of HIV for test of antiviral activity. The inhibitors included saquinavir, indinavir, nelfinavir, 141W94, ritonavir (all in clinical use), and 14 cyclic ureas with a constant core structure and varying P2, P2' and P3, P3' groups. The single mutations V82F and I84V caused changes with various inhibitors ranging from 0.3- to 86-fold in Ki and from 0.1- to 11-fold in IC90. Much larger changes compared to wild type were observed for the double mutation V82F/I84V both for Ki (10-2000-fold) and for IC90 (0.7-377-fold). However, there were low correlations (r2 = 0.017-0.53) between the mutant/wild-type ratio of Ki values (enzyme resistance) and the mutant/wild-type ratio of viral IC90 values (antiviral resistance) for each of the HIV proteases and the viruses containing the identical enzyme. Assessing enzyme resistance by "vitality values", which adjust the Ki values with the catalytic efficiencies (kcat/Km), caused no significant improvement in the correlation with antiviral resistance. Therefore, our data suggest that measurements of enzyme inhibition with mutant proteases may be poorly predictive of the antiviral effect in resistant viruses even when mutations are restricted to the protease gene.     

Continuous arterial infusion of protease inhibitor with supplementary therapy for the patients with severe acute pancreatitis--clinical effect of arterial injection of ulinastatin

We treated five patients with severe acute pancreatitis by continuous arterial infusion (CAI) of protease inhibitor, nafamostat mesilate. Arterial injection (AI) of ulinastatin was performed in four cases and AI of antibiotics (IPM/CS) was done in one case, as supplemental therapies of CAI. Abdominal pain disappeared in 7.9 hours on the average, abdominal tenderness disappeared in 5.0 days and laboratory data lately recovered. All five cases treated by these therapies were cured without hemodialysis or surgical treatment in acute phase. AI of ulinastatin through arterial infusion catheter is pharmacokinetically more effective, because it yields a relatively high concentration of the drug at the acting site when compared with that of intravenous injection. Furthermore ulinastatin inhibits different types of protease from nafamostat mesilate. Therefore the clinical effect of CAI of nafamostat mesilate is enhanced by the combined therapy with AI of ulinastatin. It is also suggested that arterial injection of ulinastatin might be effective for the control of abdominal pain and that arterial injection of antibiotics might have an advantage on prevention of infectious pancreatic necrosis.     

Arthralgias and cryoglobulinemia during protease inhibitor therapy in a patient infected with human immunodeficiency virus and hepatitis C virus

The effect of pre- and postnatal maternal dietary fatty acid composition on neurodevelopment in rat pups was studied. Timed pregnant dams were fed, beginning on d 2 of gestation and throughout lactation, either nonpurified diet (reference) or a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered among dams of the same diet group and culled to 10 pups per dam. Milk was removed from stomachs of culled pups for fatty acid analyses. From postnatal d 4 to 30, pups were assessed daily for the appearance of neurodevelopmental reflexes. Auditory brainstem conduction times were measured on postnatal d 23 and 29. Pups were killed on postnatal d 30, and cerebrums were removed for fatty acid analyses. The fatty acid composition of maternal milk and pup cerebrums reflected maternal diet with higher levels of (n-3) and (n-6) fatty acids in the fish oil and corn oil groups, respectively. The time of appearance of auditory startle was significantly delayed (P = 0.004), and auditory brainstem conduction times on postnatal d 23 and 29 were significantly longer in pups of the fish oil- than corn oil-fed dams (P 相似文献   

Combination antiretroviral therapy including a protease inhibitor eliminated the transfusion requirements of HIV-infected individuals with anemia of chronic disease

We report a case of intracoronary embolization of a ring marker on a stent sheath. The Microsnare device was unsuitable because of the distal position of the marker. After failing to retrieve the marker using an over-the-wire balloon and the two-wire technique, we succeeded in removing the marker using a balloon-on-wire system.     

Nonlactating-cow therapy with a formulation of penicillin and novobiocin: therapeutic and prophylactic effects

An experimental product incorporating 500,000 IU of procaine penicillin G and 600 mg of sodium novobiocin in 2% aluminum monostearate-peanut oil gel (10-ml dose) was infused after the final milk-out at end of lactation into all 4 mammary quarters of 56 cows that were infected in at least 1 quarter. The therapeutic and prophylactic efficacies were published in the companion report. Infusion of the product in all quarters of 5 lactating cows resulted in only slight irritation. Penicillin was eliminated by the 11th milking and novobiocin by the 5th. After infusion in the dry udder, the antibiotics were no longer detectable in serous secretion after 14 days and failed to appear in urine at the earliest (7-day) sampling after administration. Neither antibiotic was detectable in the 1st postpartum milking after nonlactating periods as short as 3 weeks.     

Hemoptysis due to MDI therapy in a patient with permanent tracheostomy: treatment with mask AeroChamber

Persistent minor hemoptysis resulted from extensive granulation tissue on the main carina and adjacent bronchi due to frequent spraying of metered-dose inhaler (MDI)-generated aerosol medications directly into a permanent tracheostomy. Salbutamol, containing oleic acid, was considered the most likely cause. After an AeroChamber equipped with an infant mask was interposed between the MDI and the tracheal stoma, hemoptysis and the pathologic changes gradually resolved.     

Acute tumor lysis syndrome due to mono-therapy with a corticosteroid in a patient with non-Hodgkin lymphoma

A 20-year-old man was hospitalised because he nearly suffocated when lying on his back. After bronchoscopy which revealed severe external compression of the airways, suddenly respiratory insufficiency developed. Because a malignant lymphoma was suspected chemotherapy was started, using monotherapy with prednisolone as the risk of acute tumour lysis syndrome (ATLS) is high with polychemotherapy of bulky tumours. Nevertheless ATLS developed, for which haemodialysis had to be applied. The tumour, a T-cell lymphoblastic non-Hodgkin lymphoma with high grade malignancy, was treated successfully with cyclophosphamide, doxorubicin, vincristine en prednisone. ATLS is characterized by hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia, lactate acidosis and acute renal failure. It can occur in the course of aggressive cytoreductive therapy in rapidly growing lymphoproliferative malignancies with large tumour size, due to massive tumour cel lysis. Corticosteroid monotherapy is a very rare cause of ATLS.     

Monitoring of antiviral therapy with quantitative evaluation of HBeAg: a comparison with HBV DNA testing

The serological endpoint of response in the treatment of chronic hepatitis B is the loss of hepatitis B virus DNA and HBeAg. Because the quantitative measurement of hepatitis B virus DNA in serum has been shown to be useful for monitoring and predicting response to interferon-alpha therapy, we decided to evaluate whether changes in HBeAg concentration could also be used in this manner. Twenty-nine patients who were initially positive for HBeAg and HBV DNA were serially evaluated for HBeAg concentration with a microparticle-capture enzyme immunoassay. HBeAg levels in serum were calculated by means of comparison with a standard curve of fluorescence rate vs. HBeAg concentration. The results, expressed in milliunits per milliliter, were compared with hepatitis B virus DNA levels determined by means of solution hybridization. The baseline HBeAg concentration proved to be the best independent predictor of response on stepwise Cox regression analysis (p = 0.026). Similar disappearance curves were observed for the two markers, although hepatitis B virus DNA became undetectable at an earlier interval in 13 of 16 cases (81%). In the 16 responders, a decline in HBeAg concentration of more than 90% was observed by wk 12 of therapy (mean +/- S.D., 95% +/- 13%). Nonresponders did not demonstrate such steep declines in HBeAg values by wk 12 (mean +/- S.D., 45% +/- 27%), and levels tended to increase at subsequent time points. We conclude that serial monitoring of HBeAg concentration with a technique that should be readily adaptable to clinical laboratories may be useful in the initial evaluation and monitoring of patients undergoing antiviral therapy.     

Satisfactory remission achieved by PUVA therapy in a case of crisis-type adult T-cell leukaemia/lymphoma with generalized cutaneous leukaemic cell infiltration

We used PUVA therapy in a patient with crisis-type adult T-cell leukaemia/lymphoma and generalized cutaneous leukaemic cell infiltration. PUVA proved very effective in reducing leukaemic cells and in clearing the eruption. To understand the way in which PUVA produced a reduction in the number of leukaemic cells, we examined peripheral blood cells by light and electron microscopy. Light microscopy was of little help, but electron microscopy revealed that PUVA induced apoptosis-like changes in circulating leukaemic cells. This suggests that apoptosis-like changes in leukaemic cells might be the reason for the success of this treatment.     

Treatment response and durability of a double protease inhibitor therapy with saquinavir and ritonavir in an observational cohort of HIV-1-infected individuals

OBJECTIVE: To evaluate treatment response, durability and tolerance of a four-drug regimen including saquinavir and ritonavir in combination with either zidovudine/lamivudine or stavudine/lamivudine. DESIGN: Observational cohort of HIV-positive individuals. METHODS: Viral load, CD4+ and CD8+ T lymphocyte counts were assessed at intervals of 1-3 months in subjects commencing therapy between July 1996 and November 1996. Adverse events were evaluated as well as risk factors for therapeutic failures. RESULTS: A group of 56 male patients were included and followed for 48 weeks. Of these, 66% had already taken a protease inhibitor. Viral load dropped by a median 1.98 log10 HIV RNA copies/ml from baseline (interquartile range: 1.49-2.46) and became undetectable (< 400 copies/ml) in 68% of patients. Response varied: 9% were non-responders (HIV RNA reduction < 0.5 log10 copies/ml) and 23% were incomplete responders (nadir of HIV RNA > 400 copies/ml). After 48 weeks, viral load remained undetectable in 49%. Median CD4+ T lymphocyte count increased from 191 x 10(6) to 418 x 10(6) cells/l (range, 241-537 x 10(6) cells/l). Although protease inhibitor and nucleoside pretreatment selected for drug-resistant viral mutants, only the protease inhibitor experience was identified as a risk factor for therapeutic failure. Adverse events occurred in 73% of patients and led to a change of therapy in 9%. CONCLUSION: Despite advanced HIV disease and pretreatment with multiple antiretroviral drugs, a strong initial treatment response to this drug regimen was observed. However, virological failure occurred in 51% of patients after 48 weeks and frequent adverse events complicated therapy.     

The crystal structure of bikunin from the inter-alpha-inhibitor complex: a serine protease inhibitor with two Kunitz domains

Bikunin is a serine protease inhibitor found in the blood serum and urine of humans and other animals. Its sequence shows internal repetition, suggesting that it contains two domains that resemble bovine pancreatic trypsin inhibitor (BPTI). A fragment of bikunin has been crystallised, its structure solved and subsequently refined against 2.5 A data. The two BPTI-like domains pack closely together and are related by an approximate 60 degrees rotation combined with a translation. These domains are very similar to each other and other proteins with this fold. The largest variations occur in the loops responsible for protease recognition. The loops of the first domain are unobstructed by the remaining protein. However, the loops of the second domain are close to the first domain and it is possible that protease binding may be affected or, in some cases, abolished by the presence of the first domain. Thus, cleavage of the two domains could alter the substrate specificity of domain II. Bikunin has a hydrophobic patch close to the N terminus of domain I, which is the most likely site for cell-surface receptor binding. In addition, there is a basic patch at one end of domain II that may be responsible for the inhibition of calcium oxalate crystallization in urine.     

Regression of Kaposi's sarcoma during therapy with HIV-1 protease inhibitors: a prospective pilot study

BACKGROUND: Early studies using HIV protease inhibitors (PI) showed regression of Kaposi's sarcoma (KS) lesions in some patients. OBJECTIVE: Our purpose was to determine prospectively the influence of PI on HIV-related KS. METHODS: KS lesions of nine patients with progressive cutaneous disease were prospectively evaluated clinically and by means of epiluminescence microscopy before and during PI therapy. HIV viremia and CD4 cell count were measured in parallel. RESULTS: All patients experienced reduction or initial stabilization of KS lesions during the first 4 to 8 weeks of HIV-1 PI therapy. After a median follow-up of 7 months and according to AIDS Clinical Trials Groups criteria, six patients had a partial response, two showed stable disease, and in one noncompliant patient KS progressed, requiring chemotherapy. With epiluminescence microscopy, a reduction in skin surface alterations, lesional size, and color intensity was demonstrated in six of nine patients. PI induced a median decrease in viremia of 1.66 log and a median increase in the CD4 count of 49 cells/mm3. CONCLUSION: In this series, HIV PI therapy reduced or stabilized KS. The efficacy of HIV-1 PI in KS may result from the improvement in cellular immunity. These results suggest the use of PI in AIDS-related KS regardless of the level of CD4 lymphocyte count and HIV viremia.     

Regression of rectal stenosis secondary to neoplasm in an HIV1-positive patient with gancyclovir antiviral therapy: report of a case

PURPOSE: The case of a human immunodeficiency virus-positive patient with rectal stenosis caused by a tumor that completely regressed in response to gancyclovir is presented. METHODS: Several biopsies from the tumoral mass failed to show any stigmata of non-Hodgkin's lymphoma, adenocarcinoma, or Kaposi sarcoma. No parasites could be detected in rectal biopsies. Viral inclusions showing both Epstein-Barr virus and cytomegalovirus on immunostained sections suggested an unusual form of viral infection. RESULTS: Antiviral therapy (gancyclovir 10 mg/kg/day) had a dramatic effect on pain and discharge of blood, and suppressed rectal difficulties within three days of therapy. The antiviral treatment was stopped at Day 10 because of leukopenia. Endoscopic and histologic examinations revealed normal rectal mucosa after 3, 6, 9, 12, and 18 months of follow-up. CONCLUSION: This is the first case of complete and long-term regression of a rectal stenosis secondary to a tumoral mass in response to antiviral therapy in patients with human immunodeficiency virus.     

Acute therapy for cluster headache with sumatriptan: findings of a one-year long-term study

The efficacy, safety, and tolerability of subcutaneous sumatriptan in the acute treatment of cluster headache were investigated in a multicenter study over a period of up to 1 year. A total of 2,031 attacks were evaluated in 52 patients. Therapy was successful in 88% of all attacks. Freedom from pain within 15 minutes in more than 90% of all attacks treated was reported by 42% of the patients, and no decline in efficacy occurred during the course of the study. Adverse events were reported by 62% of the patients.