Snake bites by the jararacucu (Bothrops jararacussu): clinicopathological studies of 29 proven cases in Sao Paulo State, Brazil

The jararacucu, one of the most dreaded snakes of Brazil, southern Bolivia, Paraguay and northeastern Argentina, is a heavily-built pit viper which may grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal venom may be milked from its venom glands on a single occasion. It has accounted for 0.8% to 10% of series of snake bites in Sao Paulo State, Brazil. We examined 29 cases of proven jararacucu bites recruited over a 20-year period in two Sao Paulo hospitals. Severe signs of local and systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding, renal failure) were seen only in patients bitten by snakes longer than 50 cm; bites by shorter specimens were more likely to cause incoagulable blood. Fourteen patients developed coagulopathy, six local necrosis (requiring amputation in one) and five local abscesses. Two became shocked and four developed renal failure. Three patients, aged 3, 11 and 65 years, died 18.75, 27.75 and 83 h after being bitten, with respiratory and circulatory failure despite large doses of specific antivenom and intensive-care- unit management. In two patients, autopsies revealed acute renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the site of the bite and disseminated intravascular coagulation. In one survivor with chronic renal failure, renal biopsy showed bilateral cortical necrosis; the patient remains dependent on haemodialysis. Effects of polyspecific Bothrops antivenom were not impressive, and it has been suggested that anti-Bothrops and anti-Crotalus antivenoms should be given in combination.      

Effects of increasing doses of simvastatin on fasting lipoprotein subfractions, and the effect of high-dose simvastatin on postprandial chylomicron remnant clearance in normotriglyceridemic patients with premature coronary sclerosis

Postprandial hyperlipidemia has been linked to premature coronary artery disease (CAD) in fasting normotriglyceridemic patients. We investigated the effects of increasing doses of simvastatin up to 80 mg/day on fasting and postprandial lipoprotein metabolism in 18 normotriglyceridemic patients with premature CAD. Fasting lipoprotein subfractions and cholesteryl ester transfer protein (CETP) activity were determined after each 5-week dose titration (0, 20, 40 and 80 mg/day). At baseline and after treatment with simvastatin 80 mg/day, standardised Vitamin A oral fat loading tests (50 g/m2; 10 h) were carried out. Ten normolipidemic healthy control subjects matched for gender, age and BMI underwent tests without medication. Treatment with simvastatin resulted in dose-dependent reductions of fasting LDL-cholesterol, without changing cholesterol levels in the VLDL-1, VLDL-2 and IDL fractions. In addition, simvastatin decreased CETP activity dose-dependently, although HDL-cholesterol remained unchanged. Simvastatin 80 mg/day decreased fasting plasma triglycerides (TG) by 26% (P < 0.05), but did not decrease significantly TG levels in any of the subfractions. The TG/cholesterol ratio increased in all subfractions. The plasma TG response to the oral fat loading test, estimated as area under the curve (TG-AUC), improved by 30% (from 21.5 +/- 2.5 to 15.1 +/- 1.9 mmol h/L; P < 0.01). Treatment with simvastatin 80 mg/day improved chylomicron remnant clearance (RE-AUC) by 36% from 30.0 +/- 2.6 to 19.2 +/- 3.3 mg h/L (P < 0.01). After therapy, remnant clearance in patients was similar to controls (19.2 +/- 3.3 and 20.3 +/- 2.7 mg h/L, respectively), suggesting a normalization of this potentially atherogenic process. In conclusion, high-dose simvastatin has beneficial effects in normotriglyceridemic patients with premature CAD, due to improved chylomicron remnant clearance, besides effective lowering of LDL-cholesterol. In addition, the lipoprotein subfractions became more cholesterol-poor, as reflected by the increased TG/cholesterol ratio, which potentially makes them less atherogenic.     

Stenting of "unprotected" left main coronary artery stenoses: early and late results

Objective—To assess short and long term efficacy of coronary stent implantation for unprotected left main coronary artery stenosis.
Design—Retrospective follow up study.
Setting—Tertiary referral centre for interventional cardiology and cardiac surgery.
Patients—Eighteen consecutive patients (12 men; age 70.8 years) between May 1993 and July 1996. Ten patients presented with stable angina and underwent the procedure electively, eight patients presented either with unstable angina or myocardial infarction and underwent the procedure in emergency.
Intervention—Johnson and Johnson Palmaz-Schatz stents were used in 16 patients, and a Microstent and a Gianturco-Roubin in one patient each. An intra-aortic balloon pump was prophylactively used for two patients in the elective group. In the acute group, six required an intra-aortic balloon pump.
Main outcome measures—Procedural success rate and major adverse cardiac events.
Results—Successful stent implantation was achieved in all patients. In the elective group, no major adverse cardiac event occurred during the procedure, but one patient had to undergo repeated angioplasty before discharge. All patients of the elective group were discharged alive and there has been one non-cardiac death during a follow up of (mean (SD)) 10 (4) months. In the emergency group, one patient died during the procedure, one patient developed a non Q-wave myocardial infarction, one patient underwent emergency coronary bypass surgery, while another patient died suddenly before hospital discharge. Six patients of the emergency group were discharged alive and there has been one non-cardiac death during a follow up of 7 (4) months.
Conclusions—Elective stent implantation for unprotected left main coronary artery stenosis is safe and effective in selected stable patients. Urgent stent implantation, however, cannot be considered as a definitive procedure in emergency situation.

     

Are there differences in late outcome after PTCA for angina pectoris after non-Q wave vs Q wave myocardial infarction?

AIMS: Revascularization is thought to improve prognosis better ifischaemia persists after so-called non-Q wave myocardial infarction,than after Q-wave myocardial infarction, because it is assumedthat prognosis is better where there is less left ventricularfunction loss. This study evaluates the differences in clinicaloutcome between patients with Q wave and those with non-Q wavemyocardial infarction who underwent percutaneous transluminalcoronary angioplasty because of recurrent ischaemia. METHODS: We retrospectively analysed two consecutive groups of patientswho underwent percutaneous transluminal coronary angioplastyfor ischaemia after either a non-Q wave (n=175) or a Q wave(n=175) myocardial infarction, and who were followed for 4 years. RESULTS: Initial angioplasty success rates were similar in both groups.At follow-up there were no significant differences between thetwo patient groups in rates of death (9% vs 11%, P=ns), myocardialinfarction (3% vs 7%, P=ns) and target vessel revascularizationby repeat percutaneous angioplasty (11% vs 15%, P=ns) or coronarybypass surgery (both 7%). CONCLUSION: We conclude that elective coronary angioplasty in patients withangina pectoris after non-Q wave myocardial infarction doesnot lead to a better prognosis than after Q wave myocardialinfarction. Thus, management strategies after myocardial infarctionshould not be based on the absence or presence of Q waves onthe electrocardiogram.     

IVF过程受精失败的预测

在发明和常规应用卵胞浆内单精子注射（ICSI）之前,十多年的临床体外受精（IVF）治疗实践中,受精率低下很常见,大约有20％～35％的IVF患者受精率很低（〈35％的卵子受精）和受精完全失败（所有卵子都不受精）。虽然受精失败与精子或卵子的质量有关,但相当一部分患者受精失败与精液质量或精子功能低下有很密切相关性。最常见的是严重的少精,弱精和畸形精子症患者。     

Proof-of-concept study on the suitability of 13C-urea as a marker substance for assessment of in vivo behaviour of oral colon-targeted dosage forms

Background and purpose:

¹³C-urea may be a suitable marker to assess the in vivo fate of colon-targeted dosage forms given by mouth. We postulated that release in the colon (urease-rich segment) of ¹³C-urea from colon-targeted capsules would lead to fermentation of ¹³C-urea by bacterial ureases into ¹³CO₂. Subsequent absorption into the blood and circulation would lead to detectable ¹³C (as ¹³CO₂) in breath. If, however, release of ¹³C-urea occurred in the small intestine (urease-poor segment), we expected detectable ¹³C (as ¹³C-urea) in blood but no breath ¹³C (as ¹³CO₂). The differential kinetics of ¹³C-urea could thus potentially describe both release kinetics and indicate the gastrointestinal segment of release.

Experimental approach:

The in vivo study consisted of three experiments, during which the same group of four volunteers participated.

Key results:

The kinetic model was internally valid. The appearance of ¹³C-in breath CO₂ (F_fermented) and the appearance of ¹³C in blood as ¹³C-urea (F_{not fermented}) show a high inverse correlation (Pearson''s r=−0.981, P= 0.06). The total recovery of ¹³C (F_fermented+F_{not fermented}) averaged 99%, indicating complete recovery of the administered ¹³C via breath and blood. ¹³CO₂ exhalation was observed in all subjects. This indicates that ¹³C-urea was available in urease-rich segments, such as the caecum or colon.

Conclusions and implications:

In this proof-of-concept study, ¹³C-urea was able to provide information on both the release kinetics of a colon-targeted oral dosage form and the gastrointestinal segment where it was released.     

High-dose aspirin in addition to daily low-dose aspirin decreases platelet activation in patients before and after percutaneous coronary intervention

BACKGROUND: Activated platelets play a major role in acute vessel closure after coronary angioplasty. Although aspirin is the routine therapy during angioplasty, it only incompletely prevents acute closure. This might be due to suboptimal dosing. OBJECTIVE: First, to study the effect of additional high-dose aspirin on platelet activation during coronary angioplasty. Second, to assess the potential of the new PFA-100 analyzer to evaluate the effect of different doses of aspirin in patients undergoing angioplasty. METHODS: Fifty-one patients on 100 mg aspirin/day for at least 1 month were randomized to continuation of 100 mg aspirin/day only (Group A=24 patients), or to this regime plus a bolus of 1000 mg of aspirin given 1 day before angioplasty (Group B=27 patients). Results were compared with 15 controls. Platelet function was measured before angioplasty by the PFA-100 analyzer; platelet activation was measured by flow cytometry just before and 1 h after angioplasty. RESULTS: At baseline, Group A had significantly more activated platelets than the control group (P<.001). High-dose aspirin in Group B resulted in significantly lower platelet activation as compared with both controls (P<.001) and Group A (P<.001). During angioplasty, the number of activated platelets decreased significantly in Group A (P<.001), while there was no change in Group B (P=.6). The PFA-100 analyzer was unable to detect differences between the two treatment groups. CONCLUSIONS: The addition of high-dose aspirin to daily low-dose aspirin, 1 day before coronary angioplasty, significantly reduced the platelet activation state before and after intervention. The PFA-100 analyzer did not detect differences in the effect of low- versus high-dose aspirin on platelet function.