Defective regulation of Cl- permeability in islets of diabetic mice [C57BL/KsJ(db/db)].

Efflux of 36Cl- from prelabeled, collagenase-isolated islets of noninbred ob/ob mice, inbred diabetic [C57BL/KsJ(db/db)] mice, and nondiabetic [C57BL/KsJ(+/+)] mice was studied by nonrecirculating perifusion. Islets of both ob/ob mice and nondiabetic KsJ mice showed similar rates of basal 36Cl- efflux, D-glucose stimulation of the 36Cl- efflux, and net uptake of 36Cl- at apparent isotope equilibrium. The 36Cl- efflux in islets from both young and old KsJ-db/db mice was almost insensitive to the D-glucose concentration. The basal rate of 36Cl- efflux in islets from young and old db/db mice was increased, indicating an abnormally high Cl- permeability. It is suggested that the defective regulation of the membrane potential in B-cells from [C57BL/KsJ(db/db)] mice may at least partly be caused by a db-mediated defect in the regulation of Cl- permeability.

Aerosolized pentamidine as primary prophylaxis for Pneumocystis carinii pneumonia: efficacy, mortality and morbidity.

OBJECTIVE: Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) for patients with HIV infection has been recommended by the Centers for Disease Control and Prevention. We evaluated alternatives to routine primary PCP prophylaxis with aerosolized pentamidine. METHODS: A total of 121 HIV-infected patients with CD4+ cell counts < or = 200 x 10(6)/l or an AIDS diagnosis were enrolled in a controlled study of aerosolized pentamidine as primary PCP prophylaxis. Patients were randomly assigned to treatment (n = 61) with aerosolized pentamidine once every month or to no treatment (n = 60). Patients were evaluated for PCP, mortality, morbidity and progression of HIV disease. Morbidity was estimated from the number of days patients were unable to work due to illness, number of days hospitalized and AIDS events. RESULTS: Baseline characteristics were similar in the treatment and control groups and mean CD4+ cell counts were 116 and 107 x 10(6)/l, respectively. Eight incidents of PCP and 19 deaths were observed in the treatment group during a median follow-up of 16.4 months (range, 2.3-32.4 months). Nineteen incidents of PCP and 13 deaths, of which one was related to an acute episode of PCP, were noted in the control group. Median follow-up of controls was 18.5 months (range, 3.1-32.9 months). Patients in the treatment group were unable to work 19% of the observation time and were hospitalized for 4.3% of that time. Corresponding figures were 20 and 3.0%, respectively, in the control group. CONCLUSIONS: Aerosolized pentamidine had significant prophylactic efficacy, but we could not detect any major effect on mortality and morbidity. The overall mortality and morbidity were not markedly influenced by PCP. Clinical check-ups and treatment of acute PCP could be a justifiable alternative to drug prophylaxis with aerosolized pentamidine in selected patients.

HIV isolation and antigen detection in infected individuals and their seronegative sexual partners.

We have examined 39 couples, each consisting of one HIV-seropositive index case and one seronegative sexual partner. HIV isolations, HIV antigen (HIV-Ag) tests and HIV antibody tests were performed on samples from these 78 individuals. Results were compared with those of 68 unselected individuals. Neither HIV, nor HIV-Ag was detected in any of the seronegative individuals. HIV-Ag tests, but not HIV isolations showed positive results with a significantly lower frequency in symptomatic index cases than in unselected patients with symptoms. This indicates that the absence of HIV-Ag in the serum may be correlated with a low level of contagiousness.

HIV transmission by blood transfusions in Stockholm 1979-1985: nearly uniform transmission from infected donors.

Thirty-five out of approximately 800 known HIV-seropositive people in Stockholm by mid-1986 were blood donors during the period 1979-1986. Almost all, i.e. 349 recipients of their blood components (red blood cells, platelets, plasma) could be traced. One hundred and eighty were still alive and 112 of these on further analysis, were suspected of being infected. They were contacted and all but one agreed to be tested for HIV antibodies. Fifty recipients were found to be seropositive. They had been transfused with blood components from 14 of the 35 donors. The earliest observed transmission occurred in June 1982. The patterns of HIV transmission showed, with only one exception, that each donor who had transmitted HIV to one recipient had also transmitted it to all later recipients. Appropriate preserved sera and clinical records from five of the donors who had not transmitted the virus were found and analysed. The result indicated that these donors had acquired their HIV infection after their last blood donation. In conclusion, our study indicates that every antibody-positive donor transmits HIV to almost every recipient.

Lack of glucose-induced priming of insulin release in the perfused mouse pancreas.

Perfusion of the mouse or rat pancreas with 20 mmol D-glucose/l caused a biphasic release of insulin. The second phase was nearly constant in the mouse but rose in the rat. Repeated pulses of 8, 20 or 30 mmol D-glucose/l did not potentiate subsequent insulin responses in the mouse, whereas repeated pulses of 20 mmol/l did in the rat. When 20 mmol D-glucose/l was introduced through the mesenteric artery or aorta of the mouse, the pattern of insulin release was the same as when it was introduced through the coeliac artery. Thus, insulin secretion in mice differs from that in rats both in not showing an increasing second phase in response to continuous stimulation with glucose and also in not showing successive enhancement in the insulin response to repeated pulses of glucose.

Diabetes is not associated with a change in the elemental composition of the pancreatic B cell in diabetic C57BL KsJ-db/db mice.

Freeze-dried pancreas sections from 7-, 17- and 27-week-old genetically diabetic (db/db) and normal (+/-/+/-) mice were subjected to proton bombardment and the concentrations of 15 elements in B cells and exocrine pancreas were calculated from the characteristic X-rays emitted. In the 7-week-old diabetic animals, B cells contained significantly above-normal levels of Na and S, while exocrine pancreas contained subnormal levels of Ca, and excess Mn. The B cells from the 17-week-old diabetic animals contained subnormal levels of Cu and the exocrine pancreas of the 27-week-old diabetic animals was deficient in Cd. The 7-, 17- and 27-week-old, genetically diabetic (db/db) mice were hyperglycemic, hyperinsulinemic and heavier than age-matched normal (+/-/+/-) mice. Although significant changes were found in elemental composition when comparing both B cells and exocrine pancreas at different ages, the changes were not consistent. Therefore, it appears as if the measured elemental changes were random and not related to the onset of diabetes.

Organochlorine accumulation and stable isotope ratios in an Atlantic salmon (Salmo salar) population from the Baltic Sea.

We investigated the organochlorine accumulation (p,p'-DDE and sigmaPCB) and stable isotope ratios (N and C) in a migrating salmon (Salmo salar) population in the Baltic Sea. delta15N in the entire population ranged from 11.7 to 13.7 per thousand and delta13C ranged from -22.0 to - 19.6 per thousand. In the entire population, delta15N were weakly related to p,p'-DDE and sigmaPCB concentrations (r2 = 0.20 and 0.14, respectively). However, lipid content was a better predictor of organochlorine (OC) concentrations (r2 = 0.48 and 0.50, respectively). Lipid adjusted sigmaPCB concentrations were not related to delta15N, and lipid adjusted p,p'-DDE concentrations were only weakly related (r2 = 0.12). We divided the salmon population into three groups representing reproductive strategies: small males < 5 kg (SM); large males > 5 kg (LM); and females (F). delta15N varied between the three reproductive strategies. The mean delta15N for SM was 12.7+/-0.3 per thousand, for F was 12.9+/-0.3 per thousand, and for LM equalled 13.2+/-0.3 per thousand. Lipid adjusted OC concentrations differed between the three reproductive strategies, with the females having the highest concentrations. We conclude that the delta15N varied between reproductive strategies indicating differences in prey choice, but the lipid content was better able to predict OC concentrations than the trophic position of the salmon.

Influence of trophic status on PCB distribution in lake sediments and biota.

We investigated the relationship between trophic status and polychlorinated biphenyl (PCB) distribution in 19 Swedish lakes. We analyzed PCB in water, phytoplankton, zooplankton, fish and sediment during two sampling periods, in spring and summer. The mass of sigma PCB in the lake sediments was positively related to lake trophy, i.e. more PCBs were accumulated and buried in the sediment of eutrophic lakes than in oligotrophic lakes. In the oligotrophic lakes a greater fraction of the total PCB load was dissolved in water. We conclude that this is a result of higher sedimentation rates in eutrophic lakes and relatively lower turnover of organic carbon in the water column of the shallow, eutrophic lakes. In the stratified lakes, the amount of PCB per cubic meter in the epilimnion decreased from spring to summer. We suggest that sedimentation of plankton beneath the thermocline during stratification act as a sink process of PCBs from the epilimnion.

Incidence of symptoms and AIDS in 146 Swedish haemophiliacs and blood transfusion recipients infected with human immunodeficiency virus.

The times from infection with the human immuno-deficiency virus (HIV) to the onset of the first clinical symptom and the development of AIDS were studied prospectively in 98 haemophiliacs and 48 blood transfusion recipients infected with the virus. Patients were followed up for a median of 61 months after infection, the dates of infection being either known exactly or estimated from the interval between the last negative and first positive HIV antibody test result. The rate of progression to AIDS was significantly higher for the transfusion recipients than for the haemophiliacs. The difference in time to the occurrence of the first clinical symptom was less pronounced between the two groups, though pointing in the same direction. The results suggest that on average roughly half of all patients positive for HIV will develop some clinical sign or symptom within five to six years after infection.

[Microcirculatory disturbances in patients with advanced AIDS].

CCTV-microscopic observation of nail-fold microcirculation was made on 11 AIDS patients and 11 healthy European adults. Unique severe microcirculatory disturbances were observed in these patients: (1) severe dysfunction of automatic alternative capillary blood flow perfusion. All the capillary loops in the same microscopic field emptied at the same moment and remained empty for a long time (3-100 seconds). Subsequent filling up of the capillary loops was very slow (1-2.5 min/loop). (2) remarkable damage of endothelial cells in the capillary wall. Some parts of the capillary wall were penetrated by some heterogeneous, visible and sludgy mass, making the wall swelled and the lumen narrowed. The wall tension in all the capillaries was markedly decreased. After the capillary loops had emptied, these damaged parts of the wall still remained in the field. These findings demonstrated the deep involvement of microcirculation in the pathogenesis of AIDS, and also showed the close relationship between microcirculation and the immune condition of the organism.

[The first case of rabies in Sweden in 26 years. Inform travellers abroad about risks and treatment following suspected infection]. / Första rabiesfallet i Sverige på 26 år. Informera utlandsresenärer om risker och behandling efter misstänkt smitta.

In June 2000, a case of rabies was diagnosed in Stockholm. The patient, a 19-year-old woman, had been bitten by a dog in Thailand three months earlier. She was admitted with a 2-day history of pain and paresthesia at the exposure site (right arm), along with anxiety. Her neurological symptoms progressed, and during the following week she developed the typical signs of furious rabies. Despite intensive care, her condition deteriorated continuously, and she died 18 days after onset of symptoms. The diagnosis was not considered until five days after admission to the hospital. A saliva sample was obtained and the diagnosis confirmed by virus isolation in mouse neuroblastoma cells. Although Sweden is free of rabies, the diagnosis should be considered in patients with encephalitis after having visited a rabies endemic area. Tourists must be informed of the vital importance of post-exposure prophylaxis after suspected infection.

The effect of tadalafil on psychosocial outcomes in Swedish men with erectile distress: a multicentre, non-randomised, open-label clinical study.

A multicentre, non-randomised, open-label study assessed whether personal distress caused by erectile dysfunction (ED) affected psychosocial outcomes of tadalafil treatment. Eligible Swedish men at least 18 years old reporting > or =3-month history of ED were stratified into two groups (manifest or mild/no distress) based upon a distress question administered at enrollment. Tadalafil 20 mg was taken as needed for 8 weeks. The primary outcome was the difference between the two distress groups in change from baseline in the Psychological and Interpersonal Relationship Scales (PAIRS) spontaneity domain. Secondary outcome measures were PAIRS sexual self-confidence and time concerns domains, Life Satisfaction (LiSat-11) checklist and a Global Assessment of Treatment Response. The study also assessed tolerability. Of 662 men enrolled, 88% had manifest distress and 12% had mild/no distress. Baseline-to-endpoint changes for PAIRS domains were not significantly different between groups. Baseline-to-endpoint changes in LiSat-11 items were not significantly different between groups except for satisfaction with sexual life. Compared with men without ED, below normal baseline satisfaction with partner relationship and family life were normalised at endpoint. Over 90% of men reported improved erection and ability to engage in sexual activity. The most common treatment-emergent adverse events were headache, myalgia, dyspepsia, flushing and back pain. One man discontinued because of myalgia; 630 (95%) completed the study. In conclusion, erectile distress levels vary among patients with ED and distress can affect intra-familiar aspects of life, which may have implications for clinical practise. However, distress does not appear to hinder improvement in both mechanical and psychosocial outcomes of tadalafil treatment.

Different dynamics of insulin secretion in the perfused pancreas of mouse and rat.

The dynamics of insulin release were studied in the perfused pancreas of rats and mice. Perfusion of the rat pancreas with 20 mM D-glucose resulted in the classical biphasic release of insulin with a rising second phase. However, in normal C57BL/KsJ-mice and non-inbred mice, whether fed or starved, the second phase was nearly constant. The secretory dynamics of KsJ-mice were essentially the same, whether the glucose concentration was 30 or 20 mM, whether the medium contained 2.56 or mM Ca2+, and whether or not the medium was supplemented with 5 mM pyruvate, 5 mM glutamate, and 5 mM fumarate. Insulin secretion in these mice was almost totally inhibited by omission of Ca2+, and was markedly enhanced by 3-isobutyl-1-methylxanthine. Insulin release during the constant phase was reversed by lowering the glucose concentration. A second rise of glucose from 3 to 20 mM produced a secretory pattern very similar to the first response. These studies indicate that the dynamics of insulin secretion are somewhat different in rats and mice. Since similar results were obtained with C57BL/KsJ-mice and non-inbred mice, the liability of KsJ-mice to develop beta-cell failure when stressed by the mutated db gene is not related to the constancy of the second insulin secretory phase.