Effects of intermittent hypoxia on sympathetic activity and blood pressure in humans

Sympathetic nerve activity and arterial pressure are frequently elevated in patients with obstructive sleep apnea (OSA). The mechanisms responsible for chronic sympathetic activation and hypertension in OSA are unknown. To determine whether repetitive apneas raise sympathetic nerve activity and/or arterial pressure, awake and healthy young subjects performed voluntary end-expiratory apneas for 20 s per min for 30 min (room air apneas). To accentuate intermittent hypoxia, in a separate group of subjects, hypoxic gas (inspired O2 10%) was added to the inspiratory port for 20 s before each apnea (hypoxic apneas). Mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA, peroneal microneurography) were determined before and up to 30 min following the repetitive apneas. Following 30 hypoxic apneas (O2 saturation nadir 83.1+/-1.2%), MSNA increased from 17.4+/-2.7 to 23.4+/-2.5 bursts/min and from 164+/-28 to 240+/-35 arbitrary units respectively (P<0.01 for both; n=10) and remained elevated while MAP increased transiently from 80.5+/-3.7 to 83.1+/-3.9 mm Hg (P<0.05; n=11). In contrast, in the subjects who performed repetitive apneas during room air exposure (O2 saturation nadir 95.1+/-0.8%), MAP and MSNA did not change (n=8). End-tidal CO2 post-apnea, an index of apnea-induced hypercapnia, was similar in the 2 groups. In a separate control group, no effect of time on MAP or MSNA was noted (n=7). Thus, repetitive hypoxic apneas result in sustained sympathetic activation and a transient elevation of blood pressure. These effects appear to be due to intermittent hypoxia and may play a role in the sympathetic activation and hypertension in OSA.     

Pig xenografts to the immunocompetent rat brain: Survival rates using distinct neurotoxic lesions in the nigrostriatal pathway and two rat strains

Porcine foetal neurons for xenotransplantation in Parkinson's disease (PD) is an alternative source to human fetuses. One of the obstacles facing brain xenotransplantation is the existence of an immune response, which prevents long-term graft survival. Experimental results concerning the survival time of porcine foetal neurons implanted into the brain of immunocompetent rats have been quite different from one study to another, suggesting an effect on graft survival of uncontrolled experimental parameters. To identify such parameters, we have first analyzed the survival of porcine foetal nigral neurons at 5 and 10 weeks after implantation into the striatum of immunocompetent rats having different types of brain lesion affecting cells (quinolinic acid) or projections to the striatum (MPP+, 6-OHDA). In a second experiment, graft survival was analyzed in two strains of recipient rats (female Sprague-Dawley and male Lewis rats) in conditions of ipsilateral dopaminergic denervation using 6-OHDA. The characteristics of surviving grafts were assessed by measuring the graft volume, the number of TH+ neurons, the size of TH+ neurons soma, and CD5+ cell infiltration. Long-term survival (> or = 10 weeks) of porcine neurons could be observed in all experimental models. However, there was no significant difference in graft survival rates and characteristics of the surviving grafts between the lesioned groups, or between Sprague-Dawley and Lewis rats. Altogether, results were highly variable within groups of grafts exposed to similar experimental procedures at both 5 and 10 weeks post-grafting. We conclude that the distinct neurotoxins and host rat strains used in our experimental design are not major factors influencing the rejection time-course of primary neural xenografts.     

P50 inhibitory gating deficit is correlated with the negative symptomatology of schizophrenia

Abnormal sensory gating in schizophrenia has frequently been reported. The strength of central inhibitory pathways was measured using the P50 component of the auditory evoked potential in a conditioning-testing paradigm. The relationships between a relative decrease in P50 amplitude to repeated auditory stimuli and clinical symptoms remain controversial. Using the Positive and Negative Syndrome Scale, we studied the P50 auditory conditioning-testing paradigm in 81 schizophrenic subjects, categorized into subgroups with and without prominent negative symptoms, in comparison with 88 control subjects. We found increased ratios of testing stimuli to conditioning stimuli in both schizophrenic subgroups relative to findings in the control group. In addition, we found significantly increased mean latencies of the P50 responses to conditioning (C) and testing (T) stimuli and significantly increased T/C ratios in the subgroup with negative symptoms compared with the subgroup with non-negative symptoms.     

A review of dengue fever incidence in Kota Bharu, Kelantan, Malaysia during the years 1998-2003

Dengue is the most common and widespread arthropod borne arboviral infection in the world today. It is estimated that there are at least 100 million cases of dengue fever (DF) annually and 500,000 cases of dengue hemorrhagic fever (DHF) which require hospitalization. In Malaysia, it has become a major public health problem. Malaysia recorded 19,544 dengue cases in 1997, the highest recorded since the disease was made notifiable in the country. Of 19,544 cases, 806 were DHF with 50 deaths. The objectives of this analysis were to describe the incidence of dengue fever and dengue hemorrhagic fever in Kota Bharu, Kelantan, Malaysia for the years 1998-2003 and to explore the characteristics of dengue fever and dengue hemorrhagic fever in Kota Bharu, Kelantan, Malaysia for years 1998-2003. A total of 4,716 dengue cases were notified involving 4,476 (94.9%) DF and 240 (5.1%) DHF cases, which increased though the years. The highest incidence was in January (701 or 14.9%), while the lowest was in May (188 or 4.0%). Forty percent of cases (n=1,890) were in the 15-29 year old group. The Majority were Malays (4,062 or 86.1%) and 2,602 or 55.2% were male. A total of 4,477 cases (95%) were local cases and 4,289 or 91% came from the urban area. For priority areas, 3,772 (80%) were from priority 1. More than half the cases had positive serology results. All symptoms occurred in more than 96% of cases and fever was the commonest (99.7%). The mean values for age, temperature, systolic and diastolic blood pressure (BP) were 27.8 +/- 15.4 years, 37.9 +/- 0.90 degrees C, 115 +/- 15.2 mmHg and 73 +/- 11.1 mmHg, respectively. The mean value for the time interval between the onset of symptoms and diagnosis, onset of symptoms and notification and time of diagnosis to notification were 5.1 +/- 2.3, 5.9 +/- 2.5 and 0.8 +/- 1.1 days, respectively. There were associations between the types of dengue and classification, area and priority area. Among the symptoms, the association was only seen in joint pain. The mean significant differences between DF and DHF were found in age and systolic blood pressure. The incidence of dengue in Kota Bharu is comparable to that in Malaysia. The increase in the number of cases needs to be addressed promptly with effective surveillance, prevention and control programs.     

HIV therapy after treatment interruption in patients with multiple failure and more than 200 CD4+ T lymphocyte count

The aim of the study was to investigate the safety and efficacy of a salvage therapy initiated after interrupting treatment in patients with virological failure and more than 200 CD4(+) T lymphocyte count. In this prospective study, 77 patients who received failing regimens had stopped completely all medication for 3 months before starting an optimised regimen consisting of 3-5 drugs. Patients were tested for HIV resistance before and after treatment interruption. Discontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 1.1 log(10), a median decrease in CD4(+) T cell count of 136 x 10(6)/L and five clinical events related to HIV, but no AIDS-defining event. Eighty-seven percent of patients showed a shift from a drug resistant genotype to a wild-type genotype based on the major resistance mutations. Forty-seven percent of patients with a genotype shift reached fewer than 200 HIV RNA copies/ml of plasma 6 and 12 months after treatment resumption whereas none of those without a genotype shift did so (P = 0.03). However, the genotypic shift was not associated with a sustained virological response by multivariate analysis. The use of a new therapeutic class of compound in the salvage regimen was the only predictor of the sustained virological response. Salvage therapy with 3-5 drugs after interrupting treatment for 3 months can be a safe and effective strategy provided the HIV disease is not too advanced. Randomised trials in this population are needed to assess the clinical benefit of this strategy.     

Life-threatening gastrointestinal bleeding related to the treatment of strongyloidiasis hyperinfection in an immunocompromised patient

The clinical course and sequel of the life-threatening gastrointestinal (GI) bleeding during the treatment of strongyloides helmintic hyperinfection induced by immunosuppression in a patient with multiple myeloma is presented. A 55-year old male patient was diagnosed with strongyloides infection with stool analysis and intestinal biopsy shortly after his combined chemotherapy for myeloma. He was commenced on albendazole anthelmintic therapy. However, after initiation of the treatment he suffered life-threatening GI bleeding. Repeated endoscopies, including intraoperative enteroscopy, concluded to diffuse multifocal intestinal bleeding. The patient required huge amounts of red blood cells and plasma transfusions and correction of haemostasis with recombinant activated factor VII. Abdominal aorto-angiography showed numerous microaneurysms ("berry aneurysms") in the superior and inferior mesenteric arteries' territories. While the biopsy taken prior to the treatment with albendazole did not show evidence of vasculitis, the biopsy taken after initiation of therapy revealed leukoclastic aggregations around the vessels which was also consistent with vasculitis. These findings suggest that--in addition to direct destruction of the mucosa-vasculitis could be an important additive factor to the massive GI bleeding during the anthelmintic treatment. This might result from substances released by the worms that have been killed with anthelmintic drugs. Current guidelines advise steroids to be tapered and stopped in case of systematic parasitic infections as they reduce immunity and precipitate parasitic hyperinfection. In our pinion, steroid therapy might be of value in the management of strongyloides hyperinfection related vasculitis--in addition to the specific anthelmintic treatment. Indeed, steroid therapy of vasculitis with other means of supportive care yielded in sequel of the bleeding and in recovery of the patient.     

Knowledge, action and resistance: the selective use of pre-natal screening among Bedouin women of the Negev, Israel

The selective use of prenatal screening by Bedouin women attending Ministry of Health, maternal and child health clinics in Israel is examined. The data consist of a review of 537 prenatal care records, 16 in depth interviews with mothers, and four interviews with health personnel. These data are part of a larger study that took place between 1994-99 amongst Negev Bedouin women, part of the Palestinian Arab minority within Israel. The record review shows that the majority of women who attend prenatal care do not take up referrals for Maternal Serum Alpha Feto Protein (MSAFP) testing or for amniocentesis tests. Although many women interviewed talked about the value of prenatal screening, they also spoke of 'false alarms' that may result from testing. Similarly, women were aware that the socially preferred pattern of consanguinity in marriage amongst the Bedouin may cause medical problems, however test uptake was unrelated to consanguinity. There was a variety of views concerning the permissibility of terminating a pregnancy. This study shows that women use prenatal screening selectively in a way that helps them to balance social and medical risk.