Substance abuse and schizophrenia: effect on symptoms but not on neurocognitive function.

The authors compare symptoms and neuropsychological test performance in DSM-III schizophrenic patients who reported prior substance abuse (N = 38) with those in patients who reported no such abuse (N = 25) to determine the impact of substance abuse on the psychopathology of schizophrenia. Positive and negative symptom scores were derived from the Schedule for Affective Disorders and Schizophrenia. Sixty neuropsychological measures drawn from commonly used tests of intelligence, memory, learning, fluency, and problem solving were calculated. Separate analyses were performed on patients in a psychotic episode who were free of neuroleptics (N = 27) and on those taking maintenance neuroleptics (N = 36). Among unmedicated patients, those who reported prior substance abuse had significantly higher thought disorder scores. Among neuroleptic-medicated patients, hallucination and delusion scores were significantly higher in the patients who reported prior substance abuse. The substance abuse followed withdrawal from social relations and preceded the onset of positive symptoms. None of the neuropsychological tests discriminated between abusers and nonabusers.     

Microtubule dynamics in axons and dendrites.

We have investigated the stability, alpha-tubulin composition, and polarity orientation of microtubules (MTs) in the axons and dendrites of cultured sympathetic neurons. MT stability was evaluated in terms of sensitivity to nocodazole, a potent anti-MT drug. Nocodazole sensitivity was assayed by quantifying the loss of MT polymer as a function of time in 2 micrograms/ml of the drug. MTs in the axon and the dendrite exhibit striking similarities in their drug sensitivity. In both types of neurites, the kinetics of MT loss are biphasic, and are consistent with the existence of two types of MT polymer that depolymerize with half-times of MT polymer that depolymerize with half-times of approximately 3.5 min and approximately 130 min. We define the more rapidly depolymerizing polymer as drug-labile and the more slowly depolymerizing polymer as drug-stable. The proportion of MT polymer that is drug-stable is greater in axons (58%) than in dendrites (25%). On the basis of current understanding of the mechanism of action of nocodazole, we suggest that the drug-labile and drug-stable polymer observed in both axons and dendrites correspond to two distinct types of polymer that differ in their relative rates of turnover in vivo. In a previous study, we established that in the axon, these drug-stable and drug-labile types of MT polymer exist in the form of distinct domains on individual MTs, with the labile domain situated at the plus end of the stable domain (Baas and Black, J Cell Biol 111:495-509, 1990). Because of the great difference in drug sensitivity between the drug-labile and drug-stable MT polymer, we were able to dissect them apart by appropriate treatments with nocodazole. This permitted us to evaluate the drug-labile and drug-stable polymer in terms of polarity orientation and relative content of alpha-tubulin variants generated by posttranslational detyrosination or acetylation. In both the axon and the dendrite, the modified as well as unmodified alpha-tubulins are present in both drug-labile and drug-stable polymer, but at different levels. Specifically, the modified forms of alpha-tubulin are enriched in the drug-stable MT polymer compared to the drug-labile MT polymer. In studies on MT polarity orientation, we demonstrate that in axons, MTs are uniformly plus-end-distal, whereas in dendrites, MTs are non uniform in their polarity orientation, with roughly equal levels of the MTs having each orientation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Swallowing food without chewing; a simple way to reduce postprandial glycaemia

1. The degree to which disruption by mastication affects the glycaemic response to four different carbohydrate foods was investigated in healthy human volunteers; each food was eaten by six subjects. 2. Subjects ate meals of sweetcorn, white rice, diced apple or potato on two occasions; on one occasion they chewed the food thoroughly, on the other occasion they swallowed each mouthful without chewing it. 3. When the foods were chewed the postprandial blood glucose levels rose to levels which varied according to the food ingested. 4. Swallowing without chewing reduced the glycaemic response to each food, achieving a similar effect as administration of viscous polysaccharides or 'slow-release' carbohydrates.     

Anti-idiotypes in B-cell tumor therapy

Thirteen patients with B-cell lymphomas were treated with mouse monoclonal anti-idiotype antibodies. All but 1 of the patients in this study had received extensive prior treatment with conventional therapy for lymphoma. The treatment protocol initially included an escalating dose schedule which was intended to help us evaluate toxicity and pharmacokinetics and, eventually, to achieve appreciable levels of free mouse antibody in the circulation. The last 4 patients received substantial initial doses. Tumor sampling was performed before and during therapy for evaluation of tissue penetration by antibody. Patients received antibodies of gamma 1, 2a, or 2b isotype. None of the patients had serum paraproteins by routine clinical testing, but 6 had an idiotype protein detectable by a sensitive immunoassay at levels greater than 1 microgram/ml, two of which were greater than 200 micrograms/ml. These levels were temporarily reduced by plasma-pheresis. However, the presence of serum idiotype increased the requirement for mouse antibody to achieve tumor penetration. Another obstacle to treatment was immune response to mouse Ig that occurred in 5 of the 13 patients. Once an immune response had begun, further infusions of antibody failed to reach the tumor or induce tumor regression and were associated with toxicity. Our initial patient remains in an unmaintained complete remission 50 months after receiving antibody. Six of 12 additional patients have had objective remissions which also were clinically significant. However, these remissions were not complete. This therapy shows promise as an alternative modality for the treatment of B-cell lymphoma. We will need further studies to determine the mechanisms of the antitumor effect and to improve the clinical results.     

Milk consumption and prevalence of coronary heart disease in men and women from the Scottish Heart Health Study

This report uses cross-sectional results from the Scottish Heart Health Study to investigate whether milk consumption has an independent effect on the prevalence of coronary heart disease. Milk consumption was assessed by questionnaire in men and women aged 40–59 years (n = 10359) who participated in a survey of risk factors for coronary heart disease between 1984 and 1986. Odds ratios for coronary heart disease were calculated according to volume and type of milk consumed for subjects with and without symptoms of coronary heart disease. Statistical adjustment was made for the classicial risk factors.
A higher percentage of men and women with diagnosed coronary heart disease (CHD) usually consume low-fat milk, compared with asymptomatic controls. Odds ratios for having undiagnosed heart disease did not differ significantly with volume or type of milk. However, the odds ratios for having diagnosed heart disease were lower in the moderate (0.5–1 pint/d) milk consumption group. Patterns of milk consumption in patients diagnosed as having CHD are likely to be confounded by dietary changes post-diagnosis. Milk consumption appears to have little independent effect on the prevalence of coronary heart disease in this Scottish population.     

Alcoholism-associated spinal and femoral bone loss in abstinent male alcoholics,as measured by dual X-ray absorptiometry

Although alcoholism is a known risk factor for osteoporosis, there are few published reports on alcoholism-associated bone loss. To study alcoholism-associated bone loss, this study used a dual X-ray absorptiometry (DXA) densitometer to measure lumbar and femoral bone mineral density (BMD) in a previously little-studied population: 32 relatively healthy, nonhospitalized, Caucasian, alcoholic men with a period of abstinence longer than that previously studied (median abstinence 4.0 months, range 3 days–36 months). DXA is a new, highly precise densitometric method with many advantages over the methods used in previous studies. The subjects had statistically significant bone loss at three sites: lumbar spine, femoral neck, and Ward's triangle (multiple correction adjusted two-tailed P < 0.008). Compared to the mean BMD of sex-, age-, and race-matched norms, the subjects' average femoral neck, Ward's triangle, and lumbar BMDs were, respectively, 0.56, 0.69, and 0.57 standard deviations (SDs) below the normative values.This study was partially funded by a National Institutes of Health Short Term Research Training Grant (PHSHL 07491) to K.C.