PURPOSE: The authors determine the association, if any, between detection of human cytomegalovirus (CMV) and human immunodeficiency virus (HIV) nucleic acids and retinal lesions in patients with acquired immune deficiency syndrome. METHODS: Postmortem eyes were examined with a dissecting microscope and light microscopy. Retinal cotton-wool spots (CWS) were removed using a clean touch punch biopsy technique. Equivalent amounts of retinal tissue from the posterior pole of the retina not affected by CWS and from the retinal periphery also were studied. Polymerase chain reaction (PCR) detection of retinal cellular DNA (GA3PD gene), human CMV DNA (major immediate early gene), and HIV (gag gene) was performed using ethidium bromide and liquid hybridization detection. RESULTS: Ninety percent of CWS were positive for CMV DNA versus 22% of peripheral retinal biopsies (P < 0.025). Liquid hybridization showed similar results. Analysis of lesions in which results of both tests were positive (ethidium and liquid hybridization) versus lesions in which results of either test were negative also showed a strong association between CWS and CMV, but not HIV nucleic acids (P < 0.02). Studies of HIV showed no association between retinal CWS lesions and HIV nucleic acid; with liquid hybridization HIV, RNA was detected equally at low levels in all areas. CONCLUSION: There is a statistically significant association between the presence of human CMV nucleic acids and retinal CWS detected by PCR. There is a low level presence of HIV in the retinal tissue studied that is only detectable using liquid hybridization techniques and is not associated with a particular area or lesions in the retina; this may represent detection of HIV in blood. The presence of CMV in areas of retinal CWS may have implications for their pathogenesis, but further study is necessary because other explanations are possible.

AIDS-Related Opportunistic Infections↗

PubMed1996

PEHO or PEHO-like syndrome?

PEHO syndrome is a rare progressive infantile encephalopathy, with variable age of onset of hypotonia, convulsions, mental retardation, oedema, and optic atrophy. Neuroimaging shows cerebellar and brainstem atrophy in most instances. A PEHO-like syndrome has been described in which those affected do not have the typical changes on neuroimaging. We report four new cases, two isolated cases and two sisters, who might be part of the PEHO-like syndrome.

Abnormalities, Multiple↗

PubMed1996

Should the stage of change model be challenged?

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California↗

PubMed1996

The frequency of homozygous deletion of a developmentally regulated Vh gene (Humhv3005) is increased in patients with chronic idiopathic thrombocytopenic purpura.

Little is known of the genetic factors that may contribute to the development of chronic idiopathic thrombocytopenic purpura (cITP). We have previously shown that a developmentally regulated Vh gene (Humhv3005) is absent in 10/41 (24%) of patients with systemic lupus erythematosus while it is absent in only 7/88 (8%) of normal controls. This finding suggests that a homozygous deletion of an Ig variable (V) gene may alter the immune system and thus predispose the host to an autoimmune disorder. We have analyzed the same gene in 44 patients with cITP and found that Humhv3005 and like genes were absent in a higher percentage of patients (14 of 44, 31.8%) than they were absent in either normals (7/88, 8%, p = 0.002) or thrombocytopenic patients without cITP (6/53, 11.3%, p = 0.042); the hv3005 deletion frequency in the latter group did not differ from that in normals (P = 0.74). These data suggest that deletions of Humhv3005 and/or highly homologous Vh genes may predispose individuals to the development of cITP, and may contribute toward production of pathogenic antiplatelet antibodies.

Chronic Disease↗

PubMed1996

Factors associated with choosing a primary care career.

The factors influencing the career choices of medical students need to be understood so that the proportion of physicians entering primary care-defined as family practice, general internal medicine, general pediatrics, and general obstetrics and gynecology-can be increased. We sent a questionnaire to 474 University of California, San Diego (UCSD), School of Medicine alumni (classes of 1974, 1978, 1982, 1986, and 1990) inquiring about demographics, personal and medical school factors, and level of debt. A total of 351 alumni responded (74% response rate), and 327 of them were engaged in direct patient care (38% in primary care). Respondents who were older, female, an underrepresented minority, from a rural background, and who chose their specialty before medical school were significantly more likely to enter primary care. The primary care group was influenced by factors unrelated to the medical school environment, such as personal social values, whereas the top 3 factors rated by the non-primary care group were directly related to school environment. Many of the respondents in primary care reported that the environment at UCSD was antagonistic toward primary care. From 1974 to 1990, more students had debt and their total debt increased, although debt had little or no influence on specialty choice.

Adult↗

PubMed1996

Addiction versus stages of change models in predicting smoking cessation.

Prospective data from the California Tobacco Surveys (n = 2066) were used to perform a critical test of the Prochaska et al. (1991) stages of change model. When the stages of change model was used as a stand alone predictor, smokers in preparation at baseline were more likely to be in cessation at follow-up than smokers in pre-contemplation at baseline (ORadj = 1.9). When stage membership was combined with baseline measures of addiction including smoking behaviors and quitting history, it was not a significant predictor of future cessation. A prediction equation that combined daily vs. occasional smoking, cigarettes per day smoked, life-time quits of at least a year, and quits of more than 5 days in the previous year discriminated smokers in cessation at follow-up of 1 to 2 years better than did the stages of change model. The area under the ROC curve for the equation based on addiction measures was 69.3% vs. 55.1% for the stages of change. Cessation rates ranged from 7.7% to 35.7% for the four-category addiction equation compared with 15.1% to 24.9% for stages of change model.

California↗

PubMed1996

Detecting hemodialysis vascular access stenosis: a tracking tool.

A tool for tracking indicators of hemodialysis vascular access stenosis is described to facilitate documentation of early signs of stenosis. Prompt notification of the nephrologist, and referral to an interventional radiologist for percutaneous transluminal angioplasty may prevent more costly interventions or hospitalizations, and even loss of the permanent access. Inadequate dialysis and its complications may be avoided by nursing observation and documentation of indicators known to be predisposing factors to hemodialysis vascular access stenosis.

Arteriovenous Shunt, Surgical↗

PubMed1996

Use and safety of a new repetitive transcranial magnetic stimulator.

In order to test a new repetitive transcranial magnetic stimulator, the Dantec MagPro, we administered transcranial magnetic stimulation (TMS) at 1 Hz and 125% of motor threshold for an average of 204 s (until the coil temperature reached 40 degrees C) and 20 Hz stimulation at 100% of motor threshold for 2 s every minute for 10 min, on different days to 10 healthy volunteers. We stimulated 6 scalp positions (primary motor area (M1) and sites 5 cm anterior and posterior on each hemisphere) with an 8-shaped coil. We tested immediate and delayed memory, verbal fluency, prolactin levels and EEG at the beginning of the study and after stimulation on each day. No abnormalities were found. Motor evoked potentials evoked with 1 Hz stimulation diminished progressively in amplitude, and 1 Hz stimulation of M1 caused inhibition lasting at least 1 min in 3 of 4 subjects who were tested with 0.1 Hz stimulation before and after the 1 Hz stimulation period. This did not occur with 20 Hz stimulation. Finger tapping frequency was tested at the beginning of the study and after TMS at each scalp site. Finger tapping rate data from 6 additional subjects who were stimulated in an identical fashion with a different stimulator were also analyzed. There was an increase in tapping rate after TMS which was independent of scalp site. This was most pronounced with 1 Hz stimulation at 125% of threshold and reached statistical significance in the hand contralateral to the stimulation. The results of this study indicate that rTMS with the MagPro stimulator is safe at specific combinations of intensity, frequency and train duration.

Adult↗

PubMed1995

Influence of tobacco marketing and exposure to smokers on adolescent susceptibility to smoking.

BACKGROUND: Today the uptake of smoking is primarily an adolescent pursuit. Awareness of tobacco advertising and promotion is high, and evidence suggests that it plays a role in adolescent smoking uptake. PURPOSE: We evaluated the influence of tobacco advertising and promotion and exposure to smokers on never-smoking adolescents' susceptibility to smoking. METHODS: We used data on 3536 adolescent never smokers (those who had never even puffed on a cigarette) from the 1993 California Tobacco Survey. That survey questioned adolescents about smoking history and inclinations. For this analysis, we defined as susceptible to smoking those never smokers who said on the survey that they could not rule out independently deciding to try a cigarette soon or smoking one offered by a friend. Also for this analysis, we devised two indices: 1) a 5-point index of an individual's receptivity to tobacco advertising as determined by the number of positive responses to five survey items (recognition of advertising messages, having a favorite advertisement, naming a brand he/she might buy, owning a tobacco-related promotional item, and willingness to use a tobacco-related promotional item) and 2) an index classifying an individual's reported exposure to family and peer smoking into one of four levels. Using logistic regression, we assessed the independent importance of our indices in predicting susceptibility to smoking after adjustment for sociodemographic variables, including age, sex, and race/ethnicity, and for perceived school performance. Tests of statistical significance were two-sided. RESULTS: Receptivity to tobacco advertising and exposure to smokers were independently associated with susceptibility to smoking, but the relationship appeared stronger for receptivity to advertising. Adolescents exposed to family members and peers (n = 489) who smoked were 1.89 (95% confidence interval [CI] = 1.30-2.74) times as likely to be susceptible, whereas adolescents who scored 4 or more on the Index of Receptivity to Tobacco Marketing (n = 361) were 3.91 (95% CI = 2.38-6.42) times as likely to be susceptible as those who scored 0. Even adolescents who scored 2 (n = 1090) were 2.03 (95% CI = 1.31-3.15) times as likely to be susceptible. There was no interaction effect between score on the Index of Receptivity to Tobacco Marketing and exposure to smokers. CONCLUSION: Our results support the hypothesis that tobacco marketing may be a stronger current influence in encouraging adolescents to initiate the smoking uptake process than exposure to peer or family smokers or sociodemographic variables including perceived school performance.

Adolescent↗

PubMed1995

Medical schools and racial discrimination. The London Hospital Medical College denies selection bias.

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Ethnicity↗

PubMed1995

Dicarboxylic acid dipeptide neutral endopeptidase inhibitors.

The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described. In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50 = 5.0 nM) in vitro and in vivo. Blood levels of 21a were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys. Free drug concentrations were 10-1500 times greater than the inhibitory constant for NEP over the course of a 6 h experiment. A good correlation of free drug concentrations was obtained when comparing values determined by the ex vivo analysis to those calculated from direct HPLC measurements. Plasma atrial natriuretic factor (exogenous) levels were elevated in rats and dogs after oral administration of 19a. Urinary volume and urinary sodium excretion were also potentiated in anesthetized dogs treated with 21a.

Amino Acid Sequence↗

PubMed1995

The predictive value of cytomegalovirus retinitis for cytomegalovirus encephalitis in acquired immunodeficiency syndrome.

Cytomegalovirus (CMV) infection of the brain, optic nerves, and retinas from 47 consecutive autopsies of patients with acquired immunodeficiency syndrome (AIDS) were examined. Immunocytochemistry demonstrated CMV infection in 11 (23%) brains, two (2%) of 94 optic nerves, and 38 (40%) of 94 retinas. Ten (91%) of 11 patients with CMV encephalitis had concurrent retinitis. While 10 (42%) of 24 patients with CMV retinitis had CMV encephalitis, when the retinitis included the peripapillary region, 75% had encephalitis. Usually, the optic nerve parenchyma was not infected histologically despite extensive peripapillary retinitis. The strength of these associations suggests that CMV retinitis defines a group of patients with AIDS at risk for development of CMV encephalitis (relative risk, 9.5), particularly when the retinitis involves the peripapillary region (relative risk, 13). Furthermore, in patients with AIDS without CMV retinitis, central nervous system symptoms are unlikely to be attributable to CMV encephalitis.

AIDS-Related Opportunistic Infections↗

PubMed1995

Aspartic proteinases from the human malaria parasite Plasmodium falciparum.

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Amino Acid Sequence↗

PubMed1995

Can chemicals be loved?--A problem for 2000.

Public perception of the value of chemicals in daily life depends on an often irrational set of conclusions reached on partial or defective information often derived from single issue pressure groups. Benefits are consistently undervalued, clean water and uncontaminated food are taken for granted and changes in the pattern of disease are assumed to have occurred as a result of other kinds of intervention. If we are to ensure a proper evaluation of the place of chemicals in our lives then we will have to persuade opinion formers of the need for rational debate, inform the scientifically literate part of the population about hazard, risk, the difficult concept of safety and the dangers of mistaking association for causation. Changes in science in the field of toxicology give us a more reasonable ground for this debate than has existed in the past and the way in which these can be exploited will be discussed.

Environmental Exposure↗