Sustained bleeding from bites of hatchling leeches

Prolongation of haemostatic parameters in the host achieved by hatchlingHirudo medicinalis differs quantitatively but not qualitatively from those achieved by adult leeches. The duration and the rate of blood loss from the bite wounds, the gain in body weight of leeches and the duration of feeding each increase with successive feeding episodes. The mean duration of bleeding from bite wounds of hatchling leeches feeding for the first time on human volunteers was 43 min compared to 6 min from control incisions and 600 min in adult leeches. The mean ‘whole body’ concentration of hirudin in 2-week-old hatchlings was 10 antithrombin units (AT-U) compared to 285 AT-U in the head of each adult leech.     

Traumatic injuries of the brachial artery

Sixty-four patients with traumatic brachial artery injuries were treated. Fifty had penetrating and 14 had blunt injuries. Associated extremity and torso injuries were common. Despite an excellent vascular patency rate of 97 percent, limb loss resulted from severe soft-tissue injury and functional disability occurred due to nerve injury.     

Pharmacokinetic and tolerability profile of twice-daily saquinavir hard gelatin capsules and saquinavir soft gelatin capsules boosted with ritonavir in healthy volunteers

Objective

To evaluate the pharmacokinetics and safety of a boosted saquinavir (SQV)/ritonavir (RTV) combination, administered as either the hard gelatin capsule (HGC) or soft gelatin capsule (SGC) formulation of SQV, in 24 healthy volunteers.

Methods

This was a single‐centre, open‐label, randomized, 2 × 2 crossover study. Twelve subjects were randomized to receive SQV/RTV 1000 mg/100 mg twice daily (BID) orally for 10 days, as either the HGC or SGC formulation. The pharmacokinetic profile of SQV was determined on day 10. Subjects then crossed over to the opposite SQV formulation, and the pharmacokinetic profile was determined again on day 20. The primary analysis was the assessment of bioequivalence based on logarithmically transformed values for AUC_{(0?24 h)} and C_max for the two formulations.

Results

There was a statistically significant increase in the geometric means of all the pharmacokinetic variables evaluated for SQV‐HGC/RTV compared with SQV‐SGC/RTV. A mean AUC_{0?24 h}‐value of 15.798 µg/mL/h was reported for the HGC formulation compared with 11.655 µg/mL/h for the SGC formulation (P = 0.0043). The SQV‐HGC/RTV combination was better tolerated in terms of gastrointestinal system disorders. Furthermore, no elevations in triglycerides or total cholesterol were reported with SQV/RTV during the entire study period.

Conclusion

In healthy volunteers, RTV boosting of SQV‐HGC produces plasma exposures at least comparable to SQV‐SGC, which is accompanied by an improvement in gastrointestinal system disorders.

     

Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham heart study.

AIMS: Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key regulator of extracellular matrix degradation. We examined relations of plasma total TIMP-1 to cardiovascular risk factors and echocardiographic left ventricular (LV) structure and function in a community-based sample. METHODS AND RESULTS: We studied 1069 Framingham Heart Study participants (mean age 56 years, 58% women) free of heart failure and previous myocardial infarction. Plasma TIMP-1 was higher in men compared with women, and increased with age, body mass index and total/HDL-cholesterol ratio, but decreased with alcohol intake. Plasma TIMP-1 was also directly related to smoking, diabetes and use of anti-hypertensive treatment. Adjusting for age, sex and height, plasma TIMP-1 was positively associated with LV mass, wall thickness, relative wall thickness, end-systolic diameter, and left atrial diameter and the risk of having increased LV end-diastolic diameter or increased wall thickness, and negatively correlated with fractional shortening. Additional adjustment for clinical covariates attenuated the relations of plasma TIMP-1 to most echocardiographic measures. CONCLUSIONS: In our cross-sectional investigation, plasma total TIMP-1 was related to major cardiovascular risk factors and to indices of LV hypertrophy and systolic dysfunction. This raises the possibility that cardiovascular risk factors may influence cardiovascular remodelling via extracellular matrix degradation, which may be reflected in plasma TIMP-1 levels.     

Fuel tanker fire disaster — South Sudan experience

In the last 15 years 26 incidents involving transport of fuel have been recorded from 17 countries throughout the world. More than 1,300 people have died, and at least 791 have received burn injuries. One such devastating event was attended by the senior author in South Sudan.These incidents have been more common in third world countries and have proved a major problem for the local health services.This paper summarises the experience in South Sudan in addition to principle issues and possible causative factors then suggests relevant preventative measures to reduce similar incidents in the future.     

Chronic HIV-2 infection protects against total CD4+ cell depletion and rapid disease progression induced by SHIV89.6p challenge

OBJECTIVE: To better understand HIV-1 sexual transmission risk, we have studied the susceptibility of HIV-2-exposed, uninfected (EU) female pig-tailed macaques to intravaginal (IVAG) re-challenge with the homologous HIV-2 strain, followed by heterologous SHIV89.6p. METHODS: Nine female macaques, previously protected by a post-exposure prophylaxis (PEP) regimen, along with one mock-treated EU animal, were re-exposed to HIV-2 by the IVAG route approximately 1.5 years later. A single follow-up challenge was performed approximately 1 year later with SHIV89.6p to assess susceptibility of chronic HIV-2-infected animals to further re-infection and pathogenic effects with a heterologous virus, somewhat mimicking HIV-1. RESULTS: Eight of ten macaques (80%) became infected systemically with HIV-2, and plasma or cervicovaginal vRNA levels did not appreciably differ from prior historic non-PEP control macaques. Interestingly, all eight HIV-2-infected females were susceptible to SHIV89.6p infection by either intravenous (n = 4) or IVAG exposure (n = 4) after one inoculation. Plasma vRNA levels in these groups were controlled by week 8 and there were no decrease in CD4+ T cells > 50%. The remaining two HIV-2 EU macaques, inoculated intrarectally with SHIV89.6p, were unable to control virus replication and succumbed to disease by week 25 or week 61. CONCLUSIONS: Our findings demonstrate that successful PEP regimens to prevent an initial infection do not have any lasting protective effects. The observed lack of cross-protection against SHIV89.6p transmission among chronic HIV-2-infected macaques provides modeling support for limited epidemiologic data indicating that human HIV-2 infection does not protect against HIV-1 infection, but may serve to alter overt clinical outcome.