Persistent productive HIV infection in EBV-transformed B lymphocytes

The susceptibility to HIV infection of 14 B-cell lines established from five healthy HIV seronegative and from six HIV seropositive subjects by lymphocyte transformation with EBV and/or by lymphocyte cultivation with cyclosporin A was studied. Although the cell lines contained different proportions of CD4-positive cells, as shown by flow cytometry, all of them could be infected with the SF-2 strain of HIV. Infection was blocked by a monoclonal antibody directed against the viral attachment site of the CD4 molecule, even in a line that lacked demonstrable CD4 receptors. B-cell lines with high proportions of CD4-expressing cells produced HIV p24 antigen more rapidly and at higher concentrations than cell lines with low CD4 expression. Although HIV infection resulted in some cytopathic effects, it was possible to cultivate the infected cells for more than 8 months without refeeding the cultures with uninfected cells. Even in long-term cultures, there was a continuous production of infectious HIV, as detected by transfer of culture supernatants to other susceptible cell lines. The production of viral antigens was consistently more pronounced in the B-cell line with the highest CD4 positivity than it was in a permissive T-cell line (HUT-78) infected in the same manner. These results indicate that HIV can chronically and productively infect transformed B cells via interaction with CD4 molecules. Thus it is possible that B cells may constitute a source of infectious virus in HIV-infected EBV-positive individuals.     

SSCP analysis of paraffin wax embedded tissues in a family with an atypical form of Fabry disease

To investigate the distribution of a single base pair mutation within a family with one known case of Fabry disease, DNA from paraffin wax embedded necropsy material was studied using single-strand conformation polymorphism (SSCP) analysis. The proband, who presented with an atypical form of Fabry disease, had a G to A transition in exon 6 of the α-galactosidase A gene. This patient had mainly cardiac symptoms and late onset disease. Further cases of coronary disorders occurred in this family, including the proband's brother who died at 42 years of age of a cardiac disorder. Formalin fixed, paraffin wax embedded material from the brother and two more distant relatives was available for analysis. SSCP analysis showed that the proband's brother also carried the G to A transition. Thus, the atypical form of Fabry disease and unrelated cardiac diseases with similar clinical symptoms occurred within a single family. The variant form is rare but may account for a few of the numerous cases of cardiac disease in men and should be considered when clusters of cases of cardiac disease occur within a single family.     

DRD4 exon 3 variants are not associated with symptomatology of major psychoses in a German population

We previously reported an association of DRD4 exon 3 long alleles with delusional symptomatology, independently from psychiatric diagnoses [Am. J. Med. Genet. 105 (2001) 283; Psychiatry Res. 80 (1998) 129]. The aim of this investigation was to replicate these results in an independent sample from Germany. We studied 394 subjects, affected by bipolar disorder (n = 32), schizoaffective disorder (n = 45), and schizophrenia (n = 317). All affected subjects were evaluated using the Operational Criteria for Psychotic Illness (OPCRIT) checklist. DRD4 variants were not associated with symptomatology of major psychosis. Our present results, obtained in an independent German sample, did not confirm the association between DRD4 variants and delusional symptomatology. However it should be considered that the original sample included a much higher rate of mood disorders and this could partially explain the discrepancy.     

Substance P antagonists and mucociliary activity in rabbit

Summary Substance P (SP) is known to accelerate mucociliary (m.c.) activity in the rabbit maxillary sinus in vivo. The physiological significance of this finding was investigated by testing three putative SP antagonists. [Arg⁵, d-Trp^{7, 9}, Nle¹¹]SP_5–11 could not be used as an antagonist because it stimulated m.c. activity. [d-Arg¹, d-Trp^{7, 9}, Leu¹¹]SP had no effect on the m.c. activity changes induced by SP. [d-Pro², d-Trp^{7, 9}]SP was found to be an effective antagonist, 1 mg/kg of this drug reversibly inhibiting both the effects of 0.1 g/kg SP and the stimulating effect of 1.0 g/kg bradykinin and 30.0g/kg capsaicin; the stimulating effect of 0.5 g/kg methacholine was not inhibited. It is suggested that bradykinin and capsaicin stimulate m.c. activity at least partly by releasing SP.The results of this investigation also support the view that the accelerating effect of SP on m.c. activity reflects physiological SP-mediated protective mechanisms in the airways. It is concluded that [d-Pro², d-Trp^{7, 9}]SP is a useful pharmacological tool for studying the role of SP in the control of m.c. actvity in rabbits.     

Is reflection like soap? a critical narrative umbrella review of approaches to reflection in medical education research

Advances in Health Sciences Education - Reflection is a complex concept in medical education research. No consensus exists on what reflection exactly entails; thus far, cross-comparing empirical...     

Risk factors for Epstein–Barr virus reactivation after renal transplantation: Results of a large,multi-centre study

Epstein–Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi-centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post-transplant year. The patients were characterized pre-transplant and two weeks post-transplant by a multi-level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre-transplant EBV shedding and male sex were associated with significantly increased incidence of post-transplant EBV reactivation. Importantly, we also identified a significant association of post-transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post-transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long-term studies are paramount to support these conclusions.     

Potency mismatch for behavioral and biochemical effects by dopamine receptor antagonists: implications for the mechanism of action of clozapine

Clozapine (3.8–60.0 µmol kg^?1) did not produce any alterations in DOPA accumulation (following inhibition of cerebral aromaticl-amino acid decarboxylase) in the prefrontal cortex or in three regions of the neostriatum, i.e. the ventral, the dorso-lateral and the posterior regions, in the rat. In contrast, clozapine produced a reduction in the 5-HTP accumulation in all these brain areas, except for the prefrontal cortex. Raclopride (0.08–20.0 µmol kg^?1) produced a marked increase in DOPA accumulation in all four brain regions and an increase in 5-HTP accumulation in the dorso-lateral neostriatum (2.5–20.0 µmol kg^?1), but not in the other forebrain regions. Treatment with SCH-23390 (0.4–1.6 µmol kg^?1) resulted in increased DOPA accumulation in the ventral and posterior parts of the neostriatum. No other changes in the DOPA or 5-HTP accumulation were seen with SCH-23390. Considering the doses of these three compounds needed for suppression of conditioned avoidance behavior and for the induction of cataleptic rigidity, it is concluded that raclopride produces an increased DA synthesis at much lower doses than those needed for behavioral effects. In contrast, the behavioral effects of SCH-23390 or clozapine precedes effects on brain DA synthesis on the dose-effect curve. In fact, the only biochemical effect of clozapine, which was observed in low, yet behaviorally active doses, was a decrease in forebrain 5-HTP accumulation. In conclusion, the present results demonstrate a mismatch, in different directions for raclopride and SCH-23390, as regards the doses needed to produce effects on brain dopamine synthesis and on behavior. Thus, the biochemical effects are seen with lower doses than the behavioral effects for the DA D₂ receptor blocking agent, whereas the opposite relationship is the case for the DA D₁ receptor antagonist. Taking these two DA receptor subtypes into consideration, the possibility should be considered that clozapine produces its antipsychotic-like behavioral effects on animal behavior primarily by a blockade of brain DA D₁, rather than D₂, receptors.     

High exposures to organic solvents among graffiti removers

Summary The exposure to organic solvents among 12 graffiti removers was studied. Health effects were also assessed by structured interview and a symptom questionnaire. Blood and urine samples were collected at the end of the day of air sampling. The concentrations of dichloromethane, glycol ethers, trimethylbenzenes and N-methyl-2-pyrrolidinone in the breathing zone of each worker were measured during one working day. The 8-h time-weighted average exposure to dichloromethane ranged from 18 to 1200 mg/m³. The Swedish Permissible Exposure Limit value for dichloromethane is 120 mg/m3. The air concentrations of glycol ethers, trimethylbenzens and N-methyl-2-pyrrolidinone were low or not detectable. No exposure-related deviations in the serum concentrations of creatinine, aspartate transaminase, alanine transaminase, -glutamyl transpeptidase or hyaluronan or the urine concentrations of ₁-microglobulin, R2-microglobulin or N-acetyl--glucos-aminidase were found. Irritative symptoms of the eyes and upper respiratory tract were more prevalent than in the general population. This study demonstrates that old knowledge about work harzards is not automatically transferred to new professions. Another aspect is that the public is also exposed as the job is performed during daytime in underground stations. At least for short periods, bystanders may be exposed to high concentrations of organic solvent vapours. People with predisposing conditions, e.g. asthmatics, may risk adverse reactions.     

A cyclic adenosine monophosphate agonist elevates the b- and c-waves of the rabbit direct-current electroretinogram

The effects of the stable cyclic adenosine monophosphate analogue adenosine 3, 5-cyclic monophosphorothioate Sp-isomer (Sp-cAMPS) on the direct-current electroretinogram and the standing potential of the eye were studied. Corneal recordings were obtained from unilaterally vitrectomized albino rabbit eyes during alternating intravitreal perfusions with Sp-cAMPS and a control solution (Pharmacia eye irrigating solution). The contralateral eye was used as a control. To evaluate further the effects on the c-wave,in vivo intraretinal microelectrode measurements were made during simultaneous intravitreal perfusion of Sp-cAMPS and irrigating solution, respectively. Sp-cAMPS in concentrations of 1, 10 and 100µM was tested by corneal direct-current electroretinography. There was no significant effect on the a-wave amplitude. The b-wave amplitude was reversibly elevated at an Sp-cAMPS concentration of 100µM (p<0.01, n=7). The c-wave amplitude was reversibly elevated at a concentration of 10µM (p<0.001, n=8), and this effect was more pronounced at 100µM (p<0.001, n=7). The SP increased reversibly at a concentration of 100µM (p<0.001, n=7). Microelectrode recordings were performed with Sp-cAMPS at a concentration of 100µM. The recordings showed significant increases in both the transepithelial potential (p<0.01, n=3) and the slow PIII (p<0.01, n=3). The effects of Sp-cAMPS on the b-wave as well as on the two components of the c-wave suggest influences on both the inner retina and the retinal pigment epithelium of the rabbit eye.Abbreviations PHS Pharmacia eye irrigating solution - AMP adenosine monophosphate - Sp-cAMPS adenosine 3, 5 - cyclic monophosphorothioate Sp-isomer     

Outpatient Induction of Labor – Are Balloon Catheters an Appropriate Method?

As the number of labor inductions in high-income countries has steadily risen, hospital costs and the additional burden on obstetric staff have also increased. Outpatient induction of labor is therefore becoming increasingly important. It has been estimated that 20 – 50% of all pregnant women requiring induction would be eligible for outpatient induction. The use of balloon catheters in patients with an unripe cervix has been shown to be an effective and safe method of cervical priming. Balloon catheters are as effective as the vaginal administration of prostaglandin E ₂ or oral misoprostol. The advantage of using a balloon catheter is that it avoids uterine hyperstimulation and monitoring is less expensive. This makes balloon catheters a suitable option for outpatient cervical ripening. Admittedly, intravenous administration of oxytocin to induce or augment labor is required in approximately 75% of cases. Balloon catheters are not associated with a higher risk of maternal and neonatal infection compared to vaginal PGE ₂ . Low-risk pregnancies (e.g., post-term pregnancies, gestational diabetes) are suitable for outpatient cervical ripening with a balloon catheter. The data for high-risk pregnancies are still insufficient. The following conditions are recommended when considering an outpatient approach: strict selection of appropriate patients (singleton pregnancy, cephalic presentation, intact membranes), CTG monitoring for 20 – 40 minutes after balloon placement, the patient must be given detailed instructions about the indications for immediate readmission to hospital, and 24-hour phone access to the hospital must be ensured. According to reviewed studies, the balloon catheter remained in place between 12 hours (“overnight”) and 24 hours. The most common reason for readmission to hospital was expulsion of the balloon catheter. The advantages of outpatient versus inpatient induction of cervical ripening with a balloon catheter were the significantly shorter hospital stay, the lower costs, and higher patient satisfaction, with both procedures having been shown to be equally effective. Complication rates (e.g., vaginal bleeding, severe pain, uterine hyperstimulation syndrome) during the cervical ripening phase are low (0.3 – 1.5%); severe adverse outcomes (e.g., placental abruption) have not been reported. Compared to inpatient induction of labor using vaginal PGE ₂ , outpatient cervical ripening using a balloon catheter had a lower rate of deliveries/24 hours and a significantly higher need for oxytocin; however, hospital stay was significantly shorter, frequency of pain during the cervical ripening phase was significantly lower, and patientsʼ duration of sleep was longer. A randomized controlled study comparing outpatient cervical priming with a balloon catheter with outpatient or inpatient induction of labor with oral misoprostol would be of clinical interest. Key words: outpatient/inpatient induction of labor/cervical priming, balloon catheter, prostaglandins, efficacy, safety