Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease

Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with onset age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkage analysis studies. In all patients mutations in the amyloid precursor protein gene ( APP ) had previously been excluded. Four different PS -1 missense mutations were identified in six familial cases, two of which where autosomal dominant cases. Three mutations resulted in onset ages above 55 years, with one segregating in an autosomal dominant family with mean onset age 64 years (range 50-78 years). One PS -2 mutation was identified in a sporadic case with onset age 62 years. Our mutation data provided estimates for PS -1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively. When family history was accounted for mutation frequencies for PS -1 were 9% in familial cases and 18% in autosomal dominant cases. Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies.      

Why did persons invited to train in cardiopulmonary resuscitation not do so?

All citizens (N = 22066) aged 16 to 65 of a medium-sized Belgiantown were personally invited to CPR training sessions held intheir neighbourhood. 1152 responded by attending a trainingsession. Those who did not so respond were surveyed (randomsample N=600) for reasons of their not coming. The sample fittedwell with census data for gender, age and suburb location butnot for job, because retired persons and women at home wereover represented. 123 persons did not want to answer the questions. 116 personssaid they were already trained in CPR, 276 said they would accepton a future occasion and 82 said they would not. Three personsdid not answer this question. There was no discrimination for job, gender and suburb locationbetween those who did and did not accept a future training opportunity,nor was the existence of a heart patient among relatives. Theolder the person, the less inclined was that person to participatein CPR training (age effect x² = 17.17, d.f. = 9, P<0.05).The 276 who accepted future training, chose their workplace(221) and/or their social meeting place (club etc.) as the placewhere this future training should be held. We suggest that CPR training is well accepted and that the trainingopportunities should be given at places of work and social gatherings.     

Comparative study of the effect of muscle relaxants on the intraocular pressure

Control of intraocular pressure is a major concern in ophthalmic anesthesia, especially in the presence of glaucoma or penetrating eye injury. The use of succinylcholine under these conditions is controversial. This study was undertaken to assess the effects of the neuromuscular blocking agents succinylcholine, pancuronium, metocurine, vecuronium, and atracurium on the intraocular pressure of dogs. The study was performed on five "conditioned" mature male foxhounds. The dogs were intubated immediately after induction with thiopental 10 mg/kg and ventilated with an O2/N2O mixture (FIO2 = 0.33). The ventilation was controlled to maintain an endtidal CO2 concentration of 5 vol.%. and anesthesia maintained with a fentanyl infusion of 10 micrograms/kg per hour. Direct and continuous measurements were taken of blood pressure (MAP), central venous pressure (CVP), and intra-ocular pressure (IOP), the latter via a 22-gauge needle inserted into the anterior chamber of the eye. A force-displacement transducer was attached to the hindpaw to monitor muscle twitch following supramaximal stimulation of the anterior tibial nerve. These four measurements were displayed on a multi-channel polygraph (Figs. 1 and 2). Control values were obtained and then succinylcholine 1 mg/kg, pancuronium 0.1 mg/kg, metocurine 0.3 mg/kg, vecuronium 0.1 mg/kg, or atracurium 0.4 mg/kg were given in a randomized fashion and on different days. Measurements of heart rate (HR), MAP, CVP, and IOP were noted at 2, 5, 10, 20, and 30 min after giving the neuromuscular blocking agent. The results, as displayed on the polygraphy, indicate that the least effect on IOP and cardiovascular state followed neuromuscular blockade with vecuronium and atracurium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex-Positivity,Medical Mistrust,and PrEP Conspiracy Beliefs Among HIV-Negative Cisgender Black Sexual Minority Men in Atlanta,Georgia

Because the public health response to the disproportionate HIV burden faced by Black sexual minority men (BSMMM) has focused on sexual risk reduction and disease prevention, other vital components of sexual health (e.g., intimacy, pleasure, benefits of sex) have been often overlooked. Sex-positive describes a more open, holistic approach toward sex and sexuality that prioritizes these other components, though such an approach is rarely applied to BSMM's sexual health. For sex-positive BSMM, risk/preventive discourse may foster or exacerbate medical mistrust as a reaction to the dissonance between how these men view sexual health and how the medical establishment views it, which may discourage sexual healthcare-seeking. We assessed sex-positivity and its association with medical mistrust and PrEP conspiracy beliefs among 206 HIV-negative cisgender BSMM in Atlanta, Georgia. We performed exploratory factor analytic procedures on responses to a sex-positivity scale, followed by multivariable linear regressions to determine sex-positivity’s associations with medical mistrust and PrEP conspiracy beliefs. We extracted two sex-positivity factors: sexual freedom (α?=?0.90), reflecting openness toward casual sex and rejection of sexual mores, and essence of sex (α?=?0.77), reflecting the intimate, relational, and pleasurable qualities of sex. Sexual freedom was independently associated with perceived provider deception (β?=?0.19, CI?=?0.04, 0.34). Essence of sex was independently associated with PrEP conspiracy beliefs (β?=?0.16, CI?=?0.02, 0.31) and marginally associated with perceived provider deception (β?=?0.14, CI?=???0.00, 0.29). Healthcare providers and public health practitioners may cultivate greater trust with BSMM by incorporating a sex-positive approach into patient/participant interactions, clinical decision-making, and interventions. Improving access to sexual pleasure acknowledges BSMM’s right to optimal, holistic sexual health.

     

Fusarium endocarditis involving aortic valve following coronary artery surgery

This article describes a case of infective aortic valve endocarditisdue to Fusarium oxysporum occurring 4 years after coronary arterybypass grafting. It is the first reported case of endocarditiscaused by Fusarium.     

USE OF POST-TETANIC COUNT IN ASSESSMENT OF A REPETITIVE VECURONIUM-INDUCED NEUROMUSCULAR BLOCK

In order to evaluate the use of the post-tetanic count (PTC)method during repetitive administration of vecuronium, we studied20 patients allocated randomly to one of two groups: 10 patientsreceived droperidol-fentanyl anaesthesia (control group); 10other patients were given droperidol-fentanyl anaesthesia modifiedsubsequently by addition of 0.5% isoflurane (isoflurane group).Before tracheal intubation, a bolus dose of vecuronium 0.08mg kg^–1 was given i. v. followed by repeated doses of0.03 mg kg^–1. The twitch response of adductor polliciswas recorded after supramaximal stimulation of the ulnar nerveat the wrist using a Myograph 2000 neuromuscular transmissionanalyser. In the control group, a close correlation was foundbetween PTC and time to first reaction to train-of-four (TOF)nerve stimulation. This relationship was unchanged when comparingthe bolus dose and each of eight consecutive maintenance doses.Further, the degree and the duration of intense block were unchangedafter each of the eight maintenance doses. In the isofluranegroup, the relationship between PTC and time to first reactionto TOF stimulation remained unchanged after addition of isoflurane.However, isoflurane caused a significant prolongation of theduration of intense block and a corresponding lower PTC in allpatients. We conclude that PTC is a reliable method to evaluateintense neuromuscular block caused by vecuronium, even afterrepetitive administration of the drug and in combination with0.5% isoflurane. Presented in part at the annual meeting of the American Societyof Anesthesiologists, San Francisco, October 1988.     

Vertical Banded Gastroplasty-Gastric Bypass with and without the Interposition of Jejunum: Preliminary Report

Background: The complications of the gastric pouch in gastric bypass surgery are well known. Since the first report of this surgery 30 years ago, new technical aspects that make it safer and more effective have been implemented. Methods: As a modification of gastric bypass, the authors have performed 305 vertical banded gastroplasty-gastric bypass procedures. Two groups of patients underwent the procedure: Group I (n = 206) without a limb of jejunum interposed between the gastric pouch and the excluded stomach, and Group II (n = 99) with a limb of jejunum interposed between the pouch and the stomach. The results regarding excess weight loss and complications of the gastric pouch during the first year after surgery were compared. Results: Age, sex, initial weight, body mass index, and percentage of ideal weight were similar in both groups. Excess weight loss was also similar. The complications in Group I were 1 leak, 3 left subphrenic abscesses, 2 erosive gastritis with bleeding, 1 stenosis of the gastrojejunostomy, 1 perforated ulcer, and 4 marginal ulcers with bleeding. Two patients in Group II developed bleeding from the staple-line. Conclusions: These preliminary data suggest that complications of the gastric pouch can be reduced by interposing a limb of jejunum between the pouch and the excluded stomach. This is an early experience; long-term results are pending.     

Weibel-Palade bodies in endothelial cells as a marker for angiogenesis in brain tumors

A transmission electron microscope study was made of eight childhood brain tumors divided up into three zones, center, edge, infiltrating zone, and also of adjacent "normal-looking" brain. In seven of eight tumors, the numbers of Weibel-Palade bodies in endothelial cells were significantly increased in peripheral zones compared with central zones. A similar significant increase was observed after treatment of chick chorioallantoic membranes with tumor angiogenesis factor. It is suggested that large numbers of Weibel-Palade bodies may be a marker for proliferating endothelial cells in vivo.     

Renal immunoblastic sarcoma complicating immunosuppressive therapy for wegener granulomatosis

A renal tumor developing in a patient receiving cyclophosphamide (Cytoxan) therapy for Wegener granulomatosis is reported. The tumor was similar histologically to the "immunoblastic" sarcoma that develops in renal allograft recipients as a complication of immunosuppressive therapy. This case report strengthens the cause and effect relationship between immunosuppressive drug usage and the subsequent development of neoplasia.