Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac

It has been hypothesized that cyclooxygenase 2 specific inhibitors may increase the risk of cardiovascular (CV) thromboembolic events because of their inhibition of vascular prostacyclin synthesis and lack of an effect on platelet thromboxane A(2) production and aggregation. Thus, we analyzed the data for celecoxib and nonsteroidal anti-inflammatory drugs (NSAIDs) from the Celecoxib Long-term Arthritis Safety Study to determine the incidences of serious CV thromboembolic events. This trial included 3,987 persons randomized to celecoxib 400 mg twice daily (2,320 person-years of exposure) and 3,981 persons randomized to either ibuprofen 800 mg 3 times daily or diclofenac 75 mg twice daily (2,203 person-years). Because acetylsalicylic acid (ASA) use for CV risk prophylaxis (< or =325 mg/day) was permitted, separate analyses were performed for all patients and those not taking ASA. The incidences of serious CV thromboembolic events (myocardial infarction, stroke, CV deaths, and peripheral events) were similar, and not significantly different, between celecoxib and NSAID comparators (combined or individually) for all patients as well as the subgroup of patients not taking ASA. This observation was true both for all serious CV thromboembolic events, as well as for individual events. No increase in myocardial infarction was apparent, even in patients not taking ASA who were candidates for secondary prophylaxis for myocardial infarction. The relative risks for celecoxib versus NSAIDs for serious CV thromboembolic events were 1.1 for all patients and 1.1 for the subgroup of patients not taking ASA (95% confidence interval 0.7 to 1.6 and 0.6 to 1.9, respectively). In addition, the incidences of adverse CV events such as hypertension, edema, and congestive heart failure were similar to, or significantly lower than, NSAID comparators regardless of the use of ASA. Thus, these analyses demonstrate no increased risk of serious CV thromboembolic events associated with celecoxib compared with conventional NSAIDs and therefore do not support the hypothesis of a class adverse effect of cyclooxygenase 2 specific inhibitors on the CV system.     

Prognostic indicators in acute pancreatitis.

Several approaches have been used in an attempt to predict the severity and prognosis of attacks of acute pancreatitis. The Ranson and Glasgow criteria include a variety of simple laboratory parameters that are measured on admission and again within 48 h. They are the most widely used indices in clinical practice. The Acute Physiological and Chronic Health Evaluation II system is more complicated, but can be applied to a wide variety of conditions, especially in intensive care settings. The usefulness of this system depends on the threshold score for defining severe pancreatitis; a score of eight appears to be the most appropriate. The finding of nonperfused areas in the pancreas at contrast-enhanced computed tomography is indicative of pancreatic necrosis and portends an unfavourable prognosis. Other clinical and laboratory indices have been proposed, but the most important predictive factor of early mortality seems to be the presence and persistence of a Marshall organ failure score of two or more. This is especially true if organ dysfunction persists beyond 36 h. Radiological findings do not always correlate well with the presence of organ dysfunction, and more investigations are required.     

On-table cecoscopy : a novel diagnostic method in acute diverticulitis of the right colon

PURPOSE: Controversies abound regarding the optimal surgical management in noncomplicated diverticulitis of the right colon, ranging from a conservative approach to diverticulectomy to right hemicolectomy. One of the arguments for resection is to exclude carcinoma. However, there is significant morbidity associated with resection. We aim to introduce on-table cecoscopy as a tool to improve the diagnosis of acute diverticulitis of the right colon, exclude carcinoma, and reduce the rate of resection. METHODS: From October 1999 to June 2000, five patients presented to our unit with suspected acute appendicitis. Intraoperatively, we found a colonic inflammatory mass at either the cecum or the ascending colon. The cecum and ascending colon were mobilized, and bowel clamps were applied to the ascending colon and ileum. A bronchoscope (Olympus® BF-P200) was introduced through the appendix stump. To achieve a good endoscopic view, a limited volume of air was introduced through the working channel. RESULTS: After on-table cecoscopy, all the patients were diagnosed as having acute nonperforated diverticulitis of the right colon. They received appendicectomy, and the diverticulitis was managed conservatively. They were treated with a course of cephalosporin and metronidazole. We performed colonoscopy four weeks later and confirmed that none of them had carcinoma of the colon. CONCLUSIONS: On-table cecoscopy is a new, safe, and effective means of diagnosing acute diverticulitis of the right colon. We can confidently exclude carcinoma and reduce the amount of colonic resection in patients with noncomplicated diverticulitis of the right colon.     

Sensitivity of treponemal tests for detecting prior treated syphilis during human immunodeficiency virus infection

To evaluate the sensitivity of treponemal tests as a marker of prior syphilis in individuals with human immunodeficiency virus (HIV) infection, the syphilis serology of 109 homosexual men with a documented history of treated syphilis was compared with records of prior results and confirmed on stored serum samples. None of the HIV-seronegative individuals lost reactivity to a treponemal test, whereas 7% of the seropositive asymptomatic individuals and 38% of those with symptomatic HIV infection had loss of reactivity. Symptomatic HIV infection was associated with loss of reactivity, as a T4 lymphocyte count less than 200 X 10(6)/1, a T4-to-T8 ratio less than 0.6, a single prior episode of syphilis, and a low VDRL titer at the time of the last documented episode of syphilis. Although no conclusions can be drawn about the sensitivity of treponemal tests in patients with active syphilis and HIV infection, these data suggest that treponemal tests may not identify those previously infected with Treponema pallidum.     

Twenty-four hour ambulatory blood pressure in the Hypertension Optimal Treatment (HOT) study

BACKGROUND AND AIMS: The Hypertension Optimal Treatment (HOT) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg, there can be a further reduction of cardiovascular events, particularly myocardial infarction, with no evidence of a J-shaped curve at lower pressures. Office measurement, however, gives no information about blood pressure outside the office. This paper describes a HOT substudy in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring. METHODS: The mean age of the substudy population was 62 +/- 7 years. Substudy patients were treated for a median period of 2 years. All received the dihydropyridine calcium antagonist felodipine, while some also received an ACE-inhibitor, a beta-blocker or a diuretic. Average 24 h, day and night ambulatory blood pressure values were computed at baseline (n = 277) and during treatment (n = 347): 112 patients had been randomized to a target office diastolic blood pressure 相似文献   

Hepatocyte iron kinetics in the rat explored with an iron chelator

S ummary . The hepatocyte metabolism of ⁵⁹Fe-labelled ferritin, haemoglobin-haptoglobin and transferrin has been examined in rats. All three forms of ⁵⁹Fe became transiently available to desferrioxamine (DF) at the time they would otherwise have entered storage or alternative pathways of iron metabolism. However, differences in both the patterns of spontaneous ⁵⁹Fe reutilization by normal and iron deficient rats and the partition of chelate iron excretion between bile and urine, suggested that iron in transit within hepatocytes did not behave as a single common pool. Ferritin ⁵⁹Fe, entering a pool of non-radioactive iron the size of which is determined by liver iron stores, was chelated predominantly into the bile. Transferrin ⁵⁹Fe was distinguished by a greater reflux to the erythron in iron deficient rats, and by excretion of a larger proportion of ⁵⁹Fe chelated by DF in the urine. Haemoglobin-haptoglobin ⁵⁹Fe followed a metabolic pathway which was relatively independent of both the iron stores and DF. If the heterogeneous behaviour of rat hepatocyte transit iron has a parallel in man, alterations in the size of similar chelatable iron pools could explain the dependence of DF-induced urine and faecal iron excretion on both liver iron stores and the level of erythropoiesis.     

Oral modified insulin (HIM2) in patients with type 1 diabetes mellitus: results from a phase I/II clinical trial

An effective, orally administered insulin product would be of substantial benefit in the treatment of patients with diabetes mellitus. This phase I/II clinical trial was the first to investigate the safety and effectiveness of a single oral dose of a modified human insulin in controlling postprandial plasma glucose levels in patients with type 1 diabetes mellitus who were receiving basal continuous subcutaneous insulin infusion (CSII) therapy. Fourteen patients with type 1 diabetes mellitus were evaluated in an open-label, 2-center, dose-escalation, nonrandomized study of oral hexyl-insulin monoconjugate 2 (HIM2). After an overnight fast and prior to receiving a standardized meal (50% carbohydrates, 30% fat, 20% proteins; 650 calories), the patients received either no additional insulin (day 1), or 0.5 to 1.0 mg/kg of HIM2 (day 2). All patients received a basal insulin regimen by CSII throughout the study. Blood samples were collected for determination of glucose and insulin levels for 240 minutes post-dose. The postprandial glucose excursion versus time curves showed clear reductions in glucose values after both HIM2 doses (day 2) relative to no treatment (day 1), although the differences in the reductions were not statistically significant. When the data for both HIM2 doses were pooled, a statistically significant effect of HIM2 on glucose excursion (as measured by AUCex(30-240)) was observed. Mean +/- SD values for AUCex(30-240) were 501.35 +/- 124.1 mg. h/dL after no treatment and 375.81 +/- 215.5 mg. h/dL after HIM2 (Wilcoxon signed-rank test, P =.042). The results of this study suggest that oral HIM2, when added to a basal insulin regimen, was safe and may prove effective in controlling postprandial hyperglycemia in patients with type 1 diabetes mellitus. Further clinical investigation is necessary.     

HIV-2 protease sequences of subtypes A and B harbor multiple mutations associated with protease inhibitor resistance in HIV-1

BACKGROUND: HIV-1 protease inhibitors (PI) have been used for treating HIV-2-infected persons but little is known about amino acid mutations associated with PI resistance in HIV-2 and whether they are similar to those seen in HIV-1. OBJECTIVE: To determine the frequency of HIV-1 PI resistance-associated mutations in PI-naive HIV-2-infected individuals. DESIGN: Using PCR, protease genes were amplified from 76 individuals, directly sequenced, phylogenetically subtyped, and translated into amino acids to analyze PI-associated major and minor mutations. RESULTS: Of the 76 HIV-2 sequences, 68% belonged to subtype A and 32% to subtype B. All sequences contained at least four codon changes giving substitutions at 10, 30, 32, 36, 46, 47, 71 or 77. The frequency of these mutations was similar in subtype A and B viruses. Two major resistance-conferring mutations, 30N and 46I, were identified in one (1%) and 68 (89%) specimens, respectively. Minor mutations 10V/I, 32I, 36I, 47V, and 71V were predominant (89%-100%), followed by the rare mutation 77I (1%). Of the 76 strains, 89% harbored multiple PI resistance-associated substitutions comprising both the major 46I and minor mutations: 10V/I, 32I, 36I, 46I, 47V, 71V (76%); 10V, 32I, 36I, 46I, 47V (9%); and 10V, 32I, 36I, 46I, 47V 71V, 77I (1.3%), 10V, 32I, 46I, 47V, 71V (1.3%), and 10V, 30N, 32I, 36I, 46I, 47V, 71V (1.3%). The remaining 11% of the sequences had patterns with only minor mutations: 10V, 32I, 36I, 47V, 71V (9%) and 10V, 32I, 36I, 47V (1.3%). CONCLUSIONS: The high frequency of multiple PI-associated substitutions represent natural polymorphisms occurring in HIV-2 strains of subtypes A and B. Phenotypic and clinical studies are needed to determine the relevance of these substitutions.