D4 dopamine receptor-mediated signaling events determined in transfected Chinese hamster ovary cells

A Chinese hamster ovary (CHO) cell line stably expressing a recombinant human D4 dopamine receptor made from a synthetic gene has been used to determine potential D4-mediated signaling events. We designed and synthesized a modified gene coding for a human D4 receptor with reduced G + C content but unaltered encoded amino acids. Stable expression of this gene was obtained in two cell lines, inducible expression in CHO lacI cells and constitutive expression in HEK293 cells. In CHO lacI cells induced to express D4 receptors but not in uninduced cells, dopamine and quinpirole inhibit forskolin-stimulated cAMP accumulation and potentiate ATP-stimulated [3H]arachidonic acid release through a mechanism that requires protein kinase C but is unaffected by membrane-soluble cAMP analogs. In addition, D4 receptor activation causes an increase in the rate of extracellular acidification measured by microphysiometry. This response is unaffected by protein kinase C down-regulation but is inhibited by removal of extracellular sodium and inhibitors of NaH-1 exchange, suggesting the involvement of a Na+/H+ exchanger. All responses are blocked by clozapine and are sensitive to pertussis toxin. D4 receptors, like other G(i)/G(o)-linked receptors, mediate multiple signaling events, and the pathways activated are similar to those used by D2 and D3 receptors expressed in similar cells.     

DNA double-strand breaks measured by pulsed-field gel electrophoresis in irradiated lymphocytes from normal humans and those with Alzheimer's disease

We have previously found that radiation-induced chromosome aberrations (dicentrics) are more numerous in lymphocytes from Alzheimer's disease (AD) patients than in those from age-matched normal individuals (Tobi et al. 1990). To investigate this further, we have examined double-strand breaks (dsb) produced by gamma-irradiation in the DNA of AD and normal lymphocytes by using pulsed-field gel electrophoresis. The percentage of DNA migrating into the gels is an indirect measure of the number of dsb; we have assayed the DNA content of sequential slices of the gel by direct fluorometry and have found that the percentage migrating is dose dependent. Our results show that the level of damage is similar in AD and normal lymphocytes and preliminary assays of the rate of repair suggest that the half-time is also similar, the value being > 1 h. The latter is consistent with the known rate of rejoining of chromosome fragments in interphase lymphocytes (Pantelias and Maillie 1985). The results suggest that at a gross level dsb repair is not impaired in AD cells; however, we cannot exclude the possibility that there is misrepair or non-repair of a small fraction of the dsb, which might account for the greater radiosensitivity of the AD cells.     

A longitudinal study of bacterial vaginosis during pregnancy

OBJECTIVE: To determine the longitudinal changes in the incidence of vaginosis in pregnancy. DESIGN: A prospective study of women during pregnancy. SETTING: A District General Hospital in North-West London. SUBJECTS: Seven hundred and eighteen pregnant women attending antenatal clinics. At their first attendance and subsequently, Gram-stained vaginal smears were examined and Mycoplasma hominis and Gardnerella vaginalis were sought by culture. RESULTS: Initially, 87 (12%) women had bacterial vaginosis diagnosed on Gram-stained reading of the vaginal smears. Examination of further smears, obtained from 176 women at 36 weeks of gestation, showed that those whose vaginal flora was normal initially, and who went to term, rarely developed vaginosis (three of 127, 2.4%). Samples were obtained at 36 weeks gestation from 32 women who had bacterial vaginosis initially, and went to term. In almost 50% (15 of 32) of these a normal lactobacillus-dominated flora had regenerated. Thirty-five women (5%) had initial vaginal smears graded as intermediate. From this group, six of the 17 (35%) women from whom samples were obtained at 36 weeks gestation still had flora of an intermediate pattern; 10(59%) now had normal flora and only one (6%) had developed bacterial vaginosis. Women with bacterial vaginosis were more likely to be culture-positive for M. hominis than those with normal flora (34/78 versus 10/563, odds ratio 42.73 (18.9 to 102.3) P < 0.001), or to be culture-positive for G. vaginalis than those with normal flora (35/78 versus 21/563, odds ratio 21.0 (10.75 to 41.2) P < 0.001). CONCLUSION: Pregnant women do not commonly develop bacterial vaginosis after 16 weeks gestation, and if present, it remits spontaneously in approximately half of those who reach term. As bacterial vaginosis is associated with increased rates of second trimester miscarriage and preterm delivery, any treatment aimed at its eradication in pregnancy should be given no later than the beginning of the second trimester of pregnancy.     

Chiral resolution of cationic drugs of forensic interest by capillary electrophoresis with mixtures of neutral and anionic cyclodextrins

Chiral resolution of a number of cationic drugs of forensic interest (amphetamine, methamphetamine, cathinone, methcathinone, cathine, cocaine, propoxyphene, and various alpha-hydroxyphenethylamines) is achieved via capillary electrophoresis (CE) with added cyclodextrins (CDs), including novel mixtures of neutral and anionic CDs. In the latter studies, resolution and migration speed are readily adjusted by varying the ratio of the two added CDs, as the anionic CD acts as a counter-migrating complexing reagent. The neutral CD, heptakis(2,6-di-O-methyl)-beta-CD, was found suitable for the analysis of illicit cocaine and khat leaves (Catha edulis Forsk), which contain (-)-alpha-aminopropiophenone ((-)-cathinone), (+)-norpseudoephedrine (cathine), (-)-norephedrine, and trace levels of the phenylpentenylamines (+)-merucathinone, (+)-merucathine, and possibly (-)-pseudomerucathine. The use of mixtures of the neutral and the anionic CD (beta-CD sulfobutyl ether IV) was found suitable for the analysis of illicit amphetamine, methamphetamine, methcathinone, and propoxyphene. A model is presented for the impact of mixtures of neutral and anionic CDs on migration behavior and chiral resolution in CE.     

An outbreak of vampire bat bite in a Brazilian village

An outbreak of 26 cases of vampire bat bite in one month in the rural area of Honorópolis, a Brazilian village, is reported. All patients were bitten during the night, when they were asleep, and most bites were on their toes. No complication attributed to the bite was reported. The patients were given prophylactic antirabies serum and rabies vaccine. Control of the outbreak was achieved by visiting bat roosting sites, smearing captured vampire bats (Desmodus rotundus) with a paste of 2% warfarin in vaseline, and releasing them. No case of human or animal rabies was diagnosed in a 5-month follow-up. A possible explanation for the outbreak of bat bite is that, because of man-induced environmental modifications in their habitats, vampire bats in Honorópolis now live in the peridomiciliar area, where people are more exposed to their bites. An alternative explanation is related to the use in cattle of a pyrethroid insecticide to control the horn fly, Haematobia irritans, as both events were temporally related. The insecticide could have had a repellent effect on bats, that then started to seek alternative food sources.     

Proposed recommendations for research on biochemical markers for problematic drinking

Successful eradication of Helicobacter pylori infection in children has required long treatment regimens that may result in noncompliance with failure to eradicate this organism. Despite full compliance with shorter therapeutic regimens, such as amoxycillin and omeprazole for 2 wk, the H. pylori eradication rate is poor in children. OBJECTIVES: The aim of this study was to evaluate the efficacy of, and compliance with, a 2-wk treatment with metronidazole, omeprazole, and clarithromycin in eradicating H. pylori disease in children. METHODS: Over a 15-month period, children diagnosed to be H. pylori positive by Steiner's stain of gastric antral biopsy specimens were treated with metronidazole, omeprazole, and clarithromycin. Follow-up upper GI endoscopy was performed 6-8 wk after completion of therapy. RESULTS: Of 15 patients with H. pylori-positive antral gastritis, 11 had duodenal ulcer disease; three patients with severe abdominal pain and one with vomiting had H. pylori gastritis only. H. pylori eradication was seen in 11 of 11 (100%) patients with duodenal ulcer disease and in three of four (75%) with gastritis only; the overall success rate was 93%. Duodenal ulcer disease healed when H. pylori was eradicated in all but one patient, who at presentation had a penetrating ulcer with a duodenobiliary fistula. Fourteen of 15 patients (93%) were fully compliant, and no adverse reactions were reported. CONCLUSIONS: Two weeks of therapy with metronidazole, omeprazole, and clarithromycin is effective H. pylori therapy in children. It is well tolerated, and full compliance can be achieved.     

Developmental outcomes in children receiving resection surgery for medically intractable infantile spasms

Two-year postsurgical developmental outcomes were assessed in 24 children with infantile spasms who underwent resective surgery. The mean age of onset of infantile spasms was 12.0 weeks and the mean age at surgery was 20.8 months. Developmental outcomes were assessed using the Vineland Adaptive Behavior Scales (VABS). There was a significant increase in developmental level at 2 years postsurgery compared with presurgical levels. At 2 years postsurgery only one of the children in this series was severely retarded. The developmental outcomes of patients in the series were better than those in prior studies of symptomatic patients receiving medical treatment for infantile spasms. It is surprising that the children in the UCLA series frequently had developmental outcomes equal to and sometimes superior to other groups of children with infantile spasms, since all the UCLA patients were symptomatic, had neurologic deficits and had failed to respond to adrenocorticotrophic hormone (ACTH) and antiepileptic drugs. The 2-year postsurgery developmental outcomes were best for the children who received surgery when they were relatively young and who had the highest level of developmental attainments presurgically.     

Reproductive history, glucose tolerance, and NIDDM in Hispanic and non-Hispanic white women. The San Luis Valley Diabetes Study

OBJECTIVE: To ascertain whether childbearing would decrease oral glucose-stimulated insulin and C-peptide levels and increase the risk of NIDDM and impaired glucose tolerance in a population of Hispanic and non-Hispanic white women residing in the San Luis Valley of Colorado. Several investigators have related childbearing to subsequent abnormal glucose tolerance. RESEARCH DESIGN AND METHODS: In a population-based case-control epidemiological study, diabetic patients 20-74 yr of age (n = 196) and randomly sampled control women subjects (n = 735) underwent a glucose tolerance test, a physical examination, and an in-person standardized interview. The relations between the live-birth number and fasting and oral glucose stimulated glucose, insulin and C-peptide concentrations, and NIDDM and impaired glucose tolerance were estimated using linear or logistic regression to adjust for extraneous variables. RESULTS: In women selected as control subjects, the live-birth number was related to a significant decrease in the sum of 1- and 2-h C-peptide concentrations (coefficient = -0.077, P < 0.001) and the logarithm of the sum of 1- and 2-h insulin concentrations (coefficient = -0.014, P = 0.02). After adjustment for subscapular skin-fold thickness, the relative odds of NIDDM for the live-birth number, which was small and of borderline significance, diminished (odds ratio = 1.04 for one birth, P = 0.18). Findings were similar for impaired glucose tolerance. CONCLUSIONS: Childbearing was related to lower C-peptide and insulin levels in Hispanic and non-Hispanic women of the San Luis Valley. It had little apparent effect on later risk of NIDDM or impaired glucose tolerance.     

Delusions of parasitosis. A psychiatric disorder to be treated by dermatologists? An analysis of 33 patients

Delusions of parasitosis is a rare disorder in which patients have the false and fixed belief that they are infested by parasites. It is a psychiatric disorder, but patients usually present to a dermatologist and referral to a psychiatrist is almost always rejected. Treating a patient with delusions of parasitosis requires patience and tact. The neuroleptic pimozide is the treatment of choice, but a significant problem is convincing the patient to take the drug. We report a study of 33 patients (13 men and 20 women) with delusions of parasitosis. The mean age at onset was 56.9 years and the mean duration of symptoms before attending the department of dermatology was 1.3 years. Pimozide (Orap) was prescribed for 24 patients, but only 18 patients took it. Follow-up information was available for 18 patients: five had full remission, four were less symptomatic, five were unchanged and four had died of unrelated causes.