Central arteriovenous anastomosis to treat resistant hypertension.

PURPOSE OF REVIEW: Novel, interventional treatments have emerged in the last decade for the treatment of resistant hypertension. This review focuses on a unique device that creates a fixed calibre, central iliac arteriovenous anastomosis that is significantly different in haemodynamic and safety profile from traditional haemodialysis fistulae. The background, physiology, and clinical data to date will be presented. RECENT FINDINGS: The single, randomized, controlled clinical trial using the ROX coupler in patients with resistant hypertension demonstrated substantial reductions in both office and ambulatory blood pressure to 12-month postimplantation. There was a common, but manageable, adverse effect of upstream iliac venous stenosis causing ipsilateral lower limb oedema. There were no renal safety concerns. The mechanism of action is proposed to be mechanical by provision of a low-pressure parallel circuit attached to the high-pressure arterial system though detailed physiological evaluation is currently lacking. SUMMARY: Preliminary data using the ROX coupler to form a central arteriovenous anastomosis are very encouraging. Concerns regarding the lack of sham control are to some extent mitigated by immediate on table blood pressure reduction with opening of the coupler and will be further addressed in the ongoing pivotal, sham-controlled ROX CONTROL Hypertension2 study which should provide further robust information regarding efficacy and safety.

Cognitive reorganization during pregnancy and the postpartum period: an evolutionary perspective.

Where the non-human animal research investigating reproduction-induced cognitive reorganization has focused on neural plasticity and adaptive advantage in response to the demands associated with pregnancy and parenting, human studies have primarily concentrated on pregnancy-induced memory decline. The current review updates Henry and Rendell's 2007 meta-analysis, and examines cognitive reorganization as the result of reproductive experience from an adaptationist perspective. Investigations of pregnancy-induced cognitive change in human females may benefit by focusing on areas, such as social cognition, where a cognitive advantage would serve a protective function, and by extending the study duration beyond pregnancy into the postpartum period.

Cost-effectiveness of lapatinib plus capecitabine in women with HER2+ metastatic breast cancer who have received prior therapy with trastuzumab.

BACKGROUND: In a phase III trial of women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab, an anthracycline, and taxanes (EGF100151), lapatinib plus capecitabine (L+C) improved time to progression (TTP) versus capecitabine monotherapy (C-only). In a trial including HER2+ MBC patients who had received at least one prior course of trastuzumab and no more than one prior course of palliative chemotherapy (GBG 26/BIG 03-05), continued trastuzumab plus capecitabine (T+C) also improved TTP. METHODS: An economic model using patient-level data from EGF100151 and published results of GBG 26/BIG 03-05 as well as other literature were used to evaluate the incremental cost per quality-adjusted life-year [QALY] gained with L+C versus C-only and versus T+C in women with HER2+ MBC previously treated with trastuzumab from the UK National Health Service (NHS) perspective. RESULTS: Expected costs were £28,816 with L+C, £13,985 with C-only and £28,924 with T+C. Corresponding QALYs were 0.927, 0.737 and 0.896. In the base case, L+C was estimated to provide more QALYs at a lower cost compared with T+C; cost per QALY gained was £77,993 with L+C versus C-only. In pairwise probabilistic sensitivity analyses, the probability that L+C is preferred to C-only was 0.03 given a threshold of £30,000. The probability that L+C is preferred to T+C was 0.54 regardless of the threshold. CONCLUSIONS: When compared against capecitabine alone, the addition of lapatinib has a cost-effectiveness ratio exceeding the threshold normally used by NICE. Compared with T+C, L+C is dominant in the base case and approximately equally likely to be cost-effective in probabilistic sensitivity analyses over a wide range of threshold values.

The association of enterotoxigenic and enteropathogenic Escherichia coli and other enteric pathogens with childhood diarrhoea in Yugoslavia.

The presence of enterotoxigenic and enteropathogenic Escherichia coli (ETEC and EPEC, respectively) was investigated in stool specimens of 1082 preschool children with diarrhoea and in stools of 335 healthy controls in localities in southern Yugoslavia, as well as in 566 children with diarrhoea and in 231 controls living in northern part of the country, during the seasonal peak (August-November) of enteric diseases in 1986. ETEC were found in 114 (10.5%) children with diarrhoea and in 14 (4.2%) controls (P less than 0.001) in the southern part, and in 26 (4.6%) ill children and one (0.4%) well child (P less than 0.005) in the northern part of Yugoslavia. EPEC were isolated from stools of 85 (7.9%) children with diarrhoea and of 14 (4.2%) well children (P less than 0.05) in localities of southern Yugoslavia, and from 22 (3.9%) ill children and from 10 (4.3%) controls in northern Yugoslavia. Nineteen EPEC strains expressed localized adherence to HEp-2 tissue culture cells; all were isolated from stools of ill children. In southern Yugoslavia, where other enteropathogens were sought, the most commonly found agents in ill children were shigellae (17.5%), rotavirus (11.8%), ETEC, and EPEC. Potential pathogens were detected in 44.5% cases of sporadic diarrhoea and in 15.8% controls. This study revealed that ETEC were associated with acute diarrhoeal disease in Yugoslav preschool children. On the other hand, the diagnosis of EPEC-diarrhoea by routine determination of serogroup established the association of these agents with sporadic diarrhoea only in the 0-2 years age categories in all investigated localities. In the less developed southern part of Yugoslavia bacteria were the predominant causative agents of enteric illness during the seasonal peak of this disease.

[Diagnostic and therapeutic aspects of pneumococcal meningitis in Africa (apropos of 119 cases)]. / Aspects diagnostiques et thérapeutiques de la méningite a pneumocoque en Afrique (à propos de 119 observations).

This study shows the extreme gravity of pneumococcal meningitis in Abidjan. The factors of bad prognosis are: male sex, coma, protein rate of the cerebral fluid equal to or higher than 3 g. Our statistical study shows evident superiority of cephacetrile to penicillin G and ampicillin.

Studies on vaccination against bacillary dysentery. 6. Protection of children by oral immunization with streptomycin-dependent Shigella strains.

A field trial of oral streptomycin-dependent mutant Shigella vaccines in five hyperendemic areas of Yugoslavia in 1969 confirmed the findings of earlier studies by demonstrating the effectiveness of these vaccines against dysentery. For the first time, a high degree of protection was demonstrated in children. The vaccines induced serotype-specific immunity against Shigella flexneri 1 and 2a and S. sonnei. Postvaccinal reactions were minor and consisted of vomiting or diarrhoea, or both, in a small proportion of children within several hours of the administration of the vaccine. These reactions, seen mainly after the first dose, were dose-dependent and could be decreased by reducing the number of live organisms. Reactions to subsequent doses were much fewer. Pretreatment with sodium bicarbonate was necessary. Under the conditions of this study, the vaccines proved to be stable with no evidence of reversion of the mutant strains to the virulent parent.

Study of live typhoid vaccine in chimpanzees.

Streptomycin-dependent Salmonella typhi containing O and H antigens was administered as a live oral antityphoid vaccine to chimpanzees. Five animals served as controls; 5 others received the vaccine 4 times at 3-day intervals; 4 further animals were given 4 doses of vaccine at 3-day intervals together with streptomycin; and 1 animal received the 4 doses of vaccine and a daily dose of streptomycin. The individual vaccine doses varied between 36x10(9) and 82x10(9) organisms, totalling about 258x10(9)Salm. typhi per animal. The chimpanzees were challenged with 26x10(9) cells of the virulent Salm. typhi Ty2 strain 10 days after immunization and followed up bacteriologically, serologically and clinically. It was observed that after this very heavy challenge the immunized animals that had received streptomycin with the vaccine were protected to some degree against the infection and showed fewer symptoms. The animal that received vaccine and streptomycin daily did not develop the disease.The authors point out that, while the strain used may have potential usefulness for the protection of man, further studies are needed to confirm the innocuity of the vaccine, to reduce the strain's reversion to streptomycin-independence, and to determine the relative effectiveness of different immunization dosages and schedules.

Studies on vaccination against bacillary dysentery. 5. Studies in Erythrocebus patas.

In earlier studies in man it has been demonstrated that streptomycin-dependent shigellae, if given orally in 5 sufficiently large doses, confer a very high type-specific protection against bacillary dysentery.In the present study, 2 groups of Erythrocebus patas monkeys were immunized with live streptomycin-dependent Shigella flexneri 2a, and a third group was not vaccinated. One of the vaccinated groups was given streptomycin with each dose of the live vaccine. The animals that received streptomycin with the vaccine were shedding these organisms in their faeces for a significantly longer period than the animals that did not receive streptomycin. A week after the last dose of vaccine, the animals were challenged with virulent Sh. flexneri 2a organisms. All the control animals developed diarrhoea and excreted challenge organisms for an average of 9 days. None of the 9 immunized animals showed pathological changes nor symptoms of dysentery. On average, they excreted challenge organisms for only 2.3 days.Immunological tests confirmed the immunity of the vaccinated animals.This study shows that 3 doses of live oral streptomycin-dependent Shigella vaccine given together with streptomycin are at least as effective as immunization with 5 doses of the same vaccine without streptomycin. Oral application of streptomycin, therefore, seems to have had an enhancing effect on the immunizing property of live oral streptomycin-dependent enteric vaccines.