Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study

Brain morphology was examined using magnetic resonance imaging in 30 first-episode patients with a schizophreniclike psychosis, 15 chronic schizophrenics, and 20 neurological controls. Statistical analyses of computer-generated measurements of regions of interest were controlled for gender, age, social class, and total brain volume. Lateral ventricular size was increased in both first-episode and chronic schizophrenic patients, with greater significance on the left than on the right side. Only the chronic patients, however, had reduced temporal lobe size, which also was greater on the left side. No major correlations of regional brain morphological measurements with cognitive functioning were found, although some measurements of verbal memory were correlated with parahippocampal size. This is a report of a preliminary study that suggests that some morphological brain changes may be present at the time of first treatment for a psychotic illness, whereas others may occur later in the course of illness. Future prospective studies may determine the clinical significance of these changes and whether they progress with the development of illness chronicity.     

Mathematical modeling of nicotine and cotinine as biological markers of environmental tobacco smoke exposure

Computer software developed in our laboratory (CMATRIX) was used to design a physiological pharmacokinetic model of nicotine absorption, distribution, metabolism and excretion in man. The model accommodates inhalation of nicotine from various environmental settings and physiological conditions in man. It was also used to predict pharmacokinetic behavior of cotinine arising from nicotine metabolism. Model-predicted variations in body-fluid nicotine levels confirm that nicotine is not an acceptable quantitative marker of environmental tobacco smoke (ETS) exposure. Though cotinine provides a more stable pattern, predicted interindividual variation suggests the need for specific strict sampling and monitoring guidelines for cotinine to be a reliable quantitative marker.     

Arthroscopic acromioplasty. Technique and results

Of forty-four patients who were treated by arthroscopic acromioplasty from July 1984 through August 1986, forty were available for analysis. The average age was 43.2 years, and 86 per cent of them had participated regularly in sports but were disabled due to symptoms of impingement. All patients had had a minimum of six months of non-operative therapy. The final diagnoses, which were based on the findings at arthroscopy and on clinical examination, plain radiographs, and arthrograms, were Stage-II impingement in twenty-four patients, a partial-thickness tear of the rotator cuff in six, and a full-thickness tear of the rotator cuff in ten. The shoulders were scored before the operation and again at follow-up. Preoperatively, thirty-six shoulders were rated as poor and four, as fair. After a minimum follow-up of twelve months (average, seventeen months), the scores had increased in all but one patient. The result was rated good or excellent in twenty-nine (73 per cent) of the forty patients: twenty of the twenty-four who had Stage-II impingement, four of the six who had a partial-thickness tear, and six of the ten who had a full-thickness tear. The over-all average time to return to work was nine days, and the average time to return to sports was 2.4 months. Of the thirty-three patients who had participated in sports, twenty-five (76 per cent) had returned to sports activity at the time of the most recent follow-up. The average time until full recovery was 3.8 months. There were no complications, and, over-all, thirty-eight (92 per cent) of the forty patients were satisfied with the result. In four patients, the result was a failure, and three of the four had a reoperation that relieved the symptoms.     

Symmetrical interdigital keratoderma of the hands

We report the case of a 26-year-old man affected by a symmetrical keratoderma localized to the interdigital spaces of the fingers. No occupational, traumatic, or irritant factors were discovered. Clinical and histological features were consistent with the diagnosis of symmetrical interdigital hyperkeratosis, a sporadic disorder described by Frei in 1926. We believe this condition to be less rare than the few cases reported in the literature would suggest.     

Origins of heterogeneous ovarian carcinomas. A molecular cytogenetic analysis of histologically benign, low malignant potential, and fully malignant components.

It is unclear whether ovarian carcinomas develop from malignant transformation of benign precursors or whether they arise de novo. Thus, histologically benign or low malignant potential components found in heterogeneous ovarian carcinomas may be remnants of pre-existing lesions that progressed to malignancy or, alternatively, elements that arose independently (de novo). In a third possible interpretation, they represent areas of malignant epithelium that matured. We evaluated clonal relationships of histological components in 10 heterogeneous ovarian carcinomas using fluorescence in situ hybridization and confocal microscopy. Detailed analysis of aneuploidy for chromosomes 8, 12, and 17 on intact paraffin sections revealed that two tumors were aneuploid in all components, two lacked abnormalities in benign-appearing components, and one lacked aneuploidy in both histologically benign and low malignant potential components. Histological appearance was significantly related to aneuploidy (P < 0.05). The distribution of aneuploidy among tumor components strongly supports the tumor progression theory and demonstrates that the de novo hypothesis is highly unlikely (P < 0.001). Results also indicate that benign-appearing components in heterogeneous ovarian carcinomas do not represent maturation of malignant tissue and suggest that some benign tumors that become cancerous may have genetic aberrations that predispose them to malignant transformation.     

Black/white comparisons of deaths preventable by medical intervention: United States and the District of Columbia 1980-1986

Blacks in the US experience increased mortality (1113 versus 745 per 100,000 males; 631 versus 411 per 100,000 females) and decreased life expectancy (63.7 years versus 70.7 years for males; 72.3 years versus 78.1 years for females); compared to Whites. In an effort to determine if the excess mortality among Black Americans might be explained by differences in access or quality of health care services, we performed a race-specific analysis of conditions for which mortality is largely avoidable given timely and appropriate medical care. Using methodology proposed by Rutstein and Charlton, mortality due to 12 causes was evaluated including tuberculosis, cervical cancer, Hodgkin's disease, rheumatic heart disease, hypertensive heart disease, acute respiratory disease, pneumonia and bronchitis, influenza, asthma, appendicitis, hernias and cholecystitis. In the US, during 1980 to 1986, an average of 17,366 deaths and 286,813 years of potential life (YPLL) before age 65 were lost each year due to all 12 sentinel causes combined. Of these causes, hypertensive heart disease, pneumonia and bronchitis, cervical cancer and asthma accounted for the greatest number of deaths. The mortality rate for all 12 causes combined among Blacks was 4.5 times that of Whites. The highest relative rates among Blacks compared to Whites were observed for tuberculosis, hypertensive heart disease and asthma. The overall mortality rate in the District of Columbia for the selected causes was 3.7 times the national rate. Compared to national rates, statistically significant elevated rates in the District were observed for tuberculosis, hypertensive heart disease and pneumonia and bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clonidine Use and Abuse Among Methadone Program Applicants and Patients

Forty-eight consecutive applicants and 30 known clonidine-abusing methadone patients at three methadone treatment programs were surveyed regarding their use of clonidine. Two distinct patterns of clonidine use emerged. Of 22 applicants who took clonidine illicitly, 15 used it primarily to decrease opioid withdrawal, as well as for its sedating effect. Applicants mostly obtained it from physicians, used an average dose of 0.37 mg at a time, and about one third believed clonidine to be addictive. In contrast, clonidine-using patients took clonidine primarily for its psychoactive effects, including the interaction with methadone, in addition to decreasing opioid withdrawal. Patients obtained clonidine frequently on the street and from family or friends, but less from physicians. The average reported dose for patients was 0.6 mg. The vast majority of these patients felt clonidine was addictive. Our findings, when coupled with the risk inherent in clonidine overdose, suggest that further research into the identification and treatment of clonidine abuse among methadone patients is warranted.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Inhibition of GABA-gated chloride channel function by arachidonic acid

The effects of arachidonic acid and its metabolites on gamma-aminobutyric acid (GABAA) receptor function were determined in rat cerebral cortical synaptoneurosomes. Incubation of synaptoneurosomes with phospholipase A2 decreased muscimol-induced 36Cl- uptake. Arachidonic acid, the major unsaturated fatty acid released by phospholipase A2, also inhibited muscimol-induced 36Cl uptake. Similar inhibition was obtained with other unsaturated fatty acids (docosahexaenoic, oleic) but not with saturated fatty acids (stearic, palmitic). The effect of arachidonic acid on muscimol responses was inhibited by bovine serum albumin (BSA), and BSA enhanced muscimol responses directly, indicating the generation of endogenous arachidonic acid in the synaptoneurosome preparation. The generation of endogenous arachidonic acid was also indicated by the ability of 2 inhibitors of arachidonic acid metabolism, indomethacin and nordihydroguaiaretic acid (NDGA), to inhibit muscimol-induced 36Cl uptake. We conclude that arachidonic acid probably has both direct and indirect actions on muscimol responses since both enzyme inhibitors inhibited muscimol responses but did not prevent the effect of exogenously added arachidonic acid. In additional experiments, arachidonic acid metabolites generated by cyclooxygenase, prostaglandins D2, E2 and F2 alpha, each decreased muscimol responses; prostaglandins F2 alpha was the most potent inhibitor. Since the unsaturated fatty acids and their metabolites are most susceptible to peroxidation, a generating system of superoxide radicals was tested on muscimol responses. A combination of xanthine and xanthine oxidase inhibited muscimol-induced 36Cl uptake in a concentration-dependent manner. We propose that the inhibition of GABAA neurotransmission by arachidonic acid and its metabolites can lead to increased neuronal excitability. This mechanism may play an important role in the development of neuronal damage following seizures or cerebral ischemia.