Increased response to antigen and histamine release in smaller sensitized canine bronchi

Presynaptic alpha 2-autoreceptors in mouse atria were characterized in terms of the alpha 2A, alpha 2B, alpha 2C and alpha 2D subtypes. Segments of the atria were preincubated with 3H-noradrenaline and then superfused and stimulated electrically. The affinity of up to 16 antagonists for the autoreceptors was assessed as (1) pEC30% values. i.e. concentrations that increased previously autoinhibited release of 3H-noradrenaline (120 pulses, 3 Hz) by 30%, and (2) pKd values against the release-inhibiting effect of 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) under conditions of no or little autoinhibition (2 trains of 20 pulses, 50 Hz, train interval 120 s). The pKd values correlated well with the pEC30% values (r = 0.98; P < 0.001; slope of regression line 0.93), indicating that UK 14,304 and released noradrenaline modulated the release of noradrenaline through pharmacologically identical receptors. Comparison with antagonist affinities for (1) prototypic native alpha 2 radioligand binding sites, (2) radioligand binding sites in COS cells transfected with alpha 2 subtype genes, and (3) previously classified presynaptic alpha 2-autoreceptors-all taken from the literature-indicated that the mouse atrial autoreceptors corresponded to the alpha 2D subtype. For example, the pKd values at mouse atrial auto-receptors correlated closely with pKd values at native alpha 2D binding sites in the bovine pineal gland (r = 0.96; P < 0.001); with pKd values at alpha 2D binding sites in COS cells transfected with the rat alpha 2D gene (r = 0.85; P < 0.01); and with pKd values at guinea-pig cerebral and atrial and mouse cerebral alpha 2D-autoreceptors (r = 0.96-0.98; P < 0.001). The antagonist pKd values at mouse atrial autoreceptors correlated less with pKd values at alpha 2A, alpha 2B and alpha 2C sites. It is concluded that the presynaptic alpha 2-autoreceptors in mouse atria are alpha 2D. This identification supports the hypothesis that at least the majority of alpha 2-autoreceptors belong to the alpha 2A/D pair of orthologous alpha 2-adrenoceptors.     

Spatial gradients of cytosolic calcium concentration in neurones during paradoxical activation by calcium

PURPOSE: To assess long-term survival following cladribine salvage treatment for previously treated patients with chronic lymphocytic leukemia. PATIENTS AND METHODS: Fifty-two patients aged 39-84 years with previously treated CLL received cladribine 0.12 mg/kg/day in 2-hour infusions for 5 days in monthly courses. Two-thirds were refractory to previous therapy, and 8 had prior fludarabine. RESULTS: Sixteen (31%) patients achieved complete response (CR) and 14 (27%) partial remission (PR) according to consensus criteria. Response correlated with clinical stage, number of previous treatment regimes, blood lymphocyte count, and lymphocyte halflife following the first cladribine course. Toxicity included pneumonia (n = 9), herpes zoster (n = 7), and septicemia (n = 2). Four patients in CR underwent high-dose chemotherapy with autologous blood stem cell support, and 2 remain in CR 48 and 60 months from start of cladribine, and 2 had relapse at 42 and 48 months, respectively. Median progression-free survival (Kaplan-Meier analysis) for CR patients was 23 months from start of cladribine treatment, and for PR patients 16 months. The projected overall survival was 80% at 3 years for CR patients, and the median survival 28 months for PR patients and 4 months for non-responding patients. CONCLUSIONS: Our previous finding of durable CRs from cladribine in advanced CLL is thus confirmed in a larger patient material, and follow-up indicate that long-term survival may be achieved.     

Instrumental treatment of recurrent lithiasis of biliary tract with stenosis of hepatico-jejunal anastomosis

The optimal treatment for recurrent stones of the biliary tract in patients previously treated by hepatic-jejunal anastomosis with Roux en Y loop is debated and the criteria are not fully defined. Age, cardiopulmonary diseases, diabetes, multiple previous surgery of the biliary tract, size, number, and type of stones are some of the factors to evaluate before choosing the most convenient approach. We present two high surgical risk patients with recurrent biliary tract stones previously treated with hepatic-jejunal anastomosis and Roux en Y loop, and treated successfully. Percutaneous lithotripsy was used and in one extracorporeal lithotripsy was associated. These techniques offered a good treatment for these patients, but we must consider the high cost of these procedures. The criteria to choose the best option should consider the risk factors and the cost effectiveness of the various possibilities.     

HIV/AIDS related knowledge, attitudes, and preventive behavior of pregnant Korean women

OBJECTIVE: To assess HIV-AIDS-related knowledge, attitudes, and preventive behavior of pregnant Korean women before designing patient and public education programs. DESIGN: Pre-experimental cross-sectional survey. POPULATION, SAMPLE, SETTING, YEARS: Convenience sample of 409 women at six prenatal clinics in Seoul, Korea, in 1993. OUTCOME MEASURES: HIV-AIDS-related knowledge, attitudes, and preventive behavior. METHODS: Self-administered questionnaires. FINDINGS: The women described high levels of knowledge about HIV and AIDS risk factors but less knowledge about transmission of the virus, as well as attitudes of rejection toward unrelated people with HIV/AIDS; 16% provided condoms for their husband's use in extramarital sex, the primary risk behavior. CONCLUSIONS: Korean women are at risk for heterosexual transmission of HIV despite knowledge of risk factors. CLINICAL IMPLICATIONS: Korean education programs for women should focus on modes of heterosexual transmission, care of individuals with HIV or AIDS, self-assessment of HIV-AIDS risk, and self protection.     

Solid-state NMR studies of the prion protein H1 fragment

Conformational changes in the prion protein (PrP) seem to be responsible for prion diseases. We have used conformation-dependent chemical-shift measurements and rotational-resonance distance measurements to analyze the conformation of solid-state peptides lacking long-range order, corresponding to a region of PrP designated H1. This region is predicted to undergo a transformation of secondary structure in generating the infectious form of the protein. Solid-state NMR spectra of specifically 13C-enriched samples of H1, residues 109-122 (MKHMAGAAAAGAVV) of Syrian hamster PrP, have been acquired under cross-polarization and magic-angle spinning conditions. Samples lyophilized from 50% acetonitrile/50% water show chemical shifts characteristic of a beta-sheet conformation in the region corresponding to residues 112-121, whereas samples lyophilized from hexafluoroisopropanol display shifts indicative of alpha-helical secondary structure in the region corresponding to residues 113-117. Complete conversion to the helical conformation was not observed and conversion from alpha-helix back to beta-sheet, as inferred from the solid-state NMR spectra, occurred when samples were exposed to water. Rotational-resonance experiments were performed on seven doubly 13C-labeled H1 samples dried from water. Measured distances suggest that the peptide is in an extended, possibly beta-strand, conformation. These results are consistent with the experimental observation that PrP can exist in different conformational states and with structural predictions based on biological data and theoretical modeling that suggest that H1 may play a key role in the conformational transition involved in the development of prion diseases.     

Depression of lipogenesis in swine adipose tissue by specific dietary fatty acids

The objective of this study was to document the influence of specific dietary fatty acids on rates of lipid synthesis and sensitivity to insulin in porcine adipose tissue. Weanling pigs were assigned to one of six groups, and each group was fed diets containing 10 g/100 g of added cornstarch or 10 g/100 g of added fatty acid. The fatty acid-enriched diets contained either a combination of 14:1 plus 16:1 (14:1/16:1 diet), 16:0, 18:0, 18:1, or 18:2 (n-6). With the exception of the cornstarch diet, all diets contained approximately 35% 14:0. Subcutaneous adipose tissue samples were collected at slaughter from the area overlying the first cranial vertebra. Fresh samples were incubated for 2 h in 20 mM glucose and 0, 10, 100 or 1,000 microU/mL of porcine insulin. The smallest adipocytes were observed in adipose tissue from pigs fed the 16:0 or 18:2 diets. Glucose incorporation into lipids was greater (P < .05) in adipose tissue from cornstarch-fed pigs than in adipose tissue from the other treatment groups. Lipogenesis was 67, 53, 35, 32, and 20% lower (P < .05) in adipose tissue from 16:0-, 14:1/16:1-, 18:0-, 18:2-, and 18:1-fed pigs, respectively, than in adipose tissue from the cornstarch-fed pigs. Insulin increased lipogenesis by 19% (P < .05) in adipose tissue from the cornstarch-fed pigs and by 15 to 40% (P < .05) in adipose tissue from the 14:1/16:1-fed pigs. Insulin did not stimulate lipogenesis (P > .4) in adipose tissue from pigs fed the 16:0, 18:0, or 18:1 diets. The data suggest that fatty acid chain length and unsaturation are determinants in the effects of dietary fat and insulin on de novo lipogenesis.     

Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus

The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha 1A, alpha 1B and alpha 1E, in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. All three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha 1A, alpha 1B and alpha 1E subunits were differentially localized. In general, alpha 1A-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha 1B antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha 1E staining pattern shared features in common with both alpha 1A and alpha 1B, with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha 1B and alpha 1E staining in the CA3 stratum lucidum with calbindin-immuno-reactivity suggested that these two calcium channels subunits may be localized presynaptically in mossy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.     

A 6-year clinical assessment of electronic facial thermography

The authors briefly report their experience regarding the opportunities offered by the use of current ultrasound methods in carotid surgery. They describe: a system for the quantification of athcromasic plaque used to monitor non-operated patients over time; ultrasound methods used to analyse the carotid wall to establish whether it can be utilised as an index of vascular aggression in hypertension, diabetes and atherosclerosis; the use of transcranial Doppler; criteria for the definition of high risk plaque; the applications of eco-color Doppler. The paper also illustrates a new pathology identified by the authors, defined as primary intimal fibrous hyperplasia, and the evolution of the carotid wall after endarterectomy. The structural characteristics of primary hyperplasia can only be shown using ultrasound given that arteriography cannot distinguish it from atheromatic stenosis. After endarterectomy the carotid wall is subject to hematic and hemodynamic stimuli which determine the type of evolution of the wall itself. The authors therefore examine the myointimal reaction, myointimal hyperplasia, early restenosis and late restenosis as different facets of the same phenomenon.     

Randomised trial comparing hysterectomy with endometrial ablation for dysfunctional uterine bleeding: psychiatric and psychosocial aspects

OBJECTIVE: To compare in psychiatric and psychosocial terms the outcome of hysterectomy and endometrial ablation for the treatment of dysfunctional uterine bleeding. DESIGN: Prospective randomised controlled trial. SETTING--Obstetrics and gynaecology department of a large teaching hospital. SUBJECTS: 204 women with dysfunctional bleeding for whom hysterectomy would have been the preferred treatment were recruited over 24 months and randomly allocated to hysterectomy (99 women) or to hysteroscopic surgery (transcervical resection (52 women) or laser ablation (53 women). MAIN OUTCOME MEASURES: Mental state, martial relationship, psychosocial and sexual adjustment in assessments conducted before the operation and one month, six months, and 12 months later. RESULTS: Both treatments significantly reduced the anxiety and depression present before the operation, and there were no differences in mental health between the groups at 12 months. Hysterectomy did not lead to postoperative psychiatric illness. Sexual interest after the operation did not vary with treatment. Overall, 46 out of 185 (25%) women reported a loss sexual interest and 50 out of 185 (27%) reported increased sexual interest. Marital relationships were unaffected by surgery. Personality and duration of dysfunctional uterine bleeding played no significant part in determining outcome. CONCLUSIONS: Hysteroscopic surgery and hysterectomy have a similar effect on psychiatric and psychosocial outcomes. There is no evidence that hysterectomy leads to postoperative psychiatric illness.     

Treatment of insomnia. Getting to the root of sleeping problems

Insomnia may be periodic and transient, as caused by situational stress, or persistent, as caused by a chronic sleep disorder. Physicians can gain much information concerning the type, probable cause, onset, and duration of insomnia through history taking. A sleep diary may reveal helpful information, and input from the patient's sleeping partner can also be valuable. Complicating disorders, such as heart failure, prostatism, or depression, should be sought and specific treatment prescribed. Chemical dependency, too, requires appropriate treatment. These measures, institution of good sleep-hygiene practices, and behavior modification may resolve sleeplessness. The primary indication for use of hypnotic agents is transient sleep disruption caused by acute stress. When an agent is chosen, onset of action, metabolism, and side effects should be considered, especially in elderly patients. Addictive agents should not be given to patients with substance abuse problems. If insomnia persists, evaluation at a sleep-disorder center is recommended to facilitate design of an appropriate therapeutic regimen.