Failure of genetically selected miniature swine to model NIDDM

Ten young adult miniature swine from a line reported to be genetically selected for glucose intolerance and eight normal controls were obtained from Colorado State University. They were consecutively exposed to 4 mo of a high-fiber, low-fat standard swine diet; 4 mo of a high-sucrose, high-fat, low-fiber diabetogenic diet; and 4 mo of excess diabetogenic diet for obesification. Results of oral glucose tolerance and intravenous insulin tolerance tests conducted at the end of each regimen were compared. Hyperglycemia was not observed in any animals after any manipulation. Insulin sensitivity was also not influenced by diet. We conclude that F7 low-K miniature swine from this colony fail to model human non-insulin-dependent diabetes.     

Left ventricle in Noonan's syndrome. Electro-vecto-echo and angiocardiographic aspects

The electrocardiographic features of Noonan's syndrome have been known for several years, but the discordance between these electrical findings and the underlying haemodynamic disorders remains unexplained. In an attempt to elucidate the genesis of electrical abnormalities, we present here a retrospective study of 14 children with Noonan's disease, aged from a few days to 16 years and evaluated by electrocardiography, vectography, one- or two-dimensional echocardiography, angiography and His bundle electrophysiology. The electrocardiographic abnormalities observed concerned ventricular depolarization and intracardiac electric conduction with, notably, a QRS axis directed towards the right upper part of the electric field and a first degree infra-hisian atrioventricular block (His bundle potentials). Vectography showed in some cases an image of inferior pseudo-necrosis due to the absence of initial inferior forces; this image is highly characteristic. In other cases the QRS loop showed an image of left segmental block which is unusual in this type or cardiac pathology (pulmonary stenosis with or without atrial septal defect of the ostium secundum type).     

The fate of isoprene inhaled by rats: comparison to butadiene

Isoprene (2-methyl-1,3-butadiene), a volatile monomer occurring in the natural environment and used in the manufacture of elastomers, is a close chemical relative of the animal carcinogen 1,3-butadiene. To obtain toxicokinetic data for inhaled isoprene, male F344 rats were exposed in groups of 30 to 14C-labeled isoprene vapor at four concentrations from 8 to 8200 ppm. The percentage of the inhaled isoprene that was metabolized decreased with increasing exposure concentration. The percentage of the total metabolites (that is, non-isoprene-retained 14C) excreted in urine and feces or expired was determined as a function of vapor concentration. About 75% of the total metabolites was excreted in urine. This was independent of inhaled isoprene concentration. After exposure to 8200 ppm, a larger percentage of the metabolites was excreted in feces than after exposure to lower concentrations. Using vacuum line techniques, blood metabolite concentrations were determined as functions of both vapor concentration and exposure duration. At one exposure concentration (1480 ppm) metabolites were measured in the nose, lungs, liver, kidney, and fat, as well as in blood. A mutagenic metabolite, isoprene diepoxide, was tentatively identified in all tissues examined. Between 0.0018 and 0.031% of the inhaled 14C label was tentatively identified as this metabolite in blood. The relative amount of the metabolites present in blood was highest for low concentrations of inhaled isoprene and for shorter exposure durations. Body fat appeared to be a reservoir for both isoprene metabolites and isoprene itself. The appearance of metabolites in the respiratory tract after short exposure durations together with low blood concentrations of isoprene indicated that substantial metabolism of inhaled isoprene in the respiratory tract may occur.     

3-(Methylnitrosamino)propionitrile: occurrence in saliva of betel quid chewers, carcinogenicity, and DNA methylation in F344 rats

3-(Methylnitrosamino)propionitrile (MNPN), a potent carcinogen in F344 rats, was detected for the first time in the saliva of betel quid chewers at levels ranging from 0.5 to 11.4 micrograms/liter. The tumorigenic properties of MNPN and its potential to methylate DNA in F344 rats were evaluated. Groups of 21 male and 21 female rats were given 60 s.c. injections over a 20-week period (total doses 0.055 and 0.23 mmol per rat). The experiment was terminated after 106 weeks. MNPN at the higher dose induced 18 (86%) malignant tumors of the nasal cavity in male and 15 (71%) in female rats. The lower dose induced nine (43%) liver tumors. Groups of four or five male F344 rats were treated with a single s.c. or i.v. injection of MNPN (0.4 mmol/kg). MNPN was also administered to rats by swabbing the oral cavity (2.21 mmol/kg). The levels of 7-methylguanine and O6-methylguanine, formed 0.5-36 h after treatment, were measured in the liver, nasal mucosa, esophagus, and oral issues. The highest levels of methylated guanines were detected in the nasal cavity independent of the route of administration. The results of this study demonstrate that MNPN is present in the saliva of betel quid chewers and is a potent carcinogen in F344 rats.     

Diagnoses of the relatives of schizotypal outpatients

Relatives of 22 schizotypal probands were evaluated for lifetime psychiatric diagnoses. Forty-four (N = 44) of the 97 available relatives were interviewed directly using the Diagnostic Interview Schedule. The rates of psychiatric diagnoses were compared with those of sixty-six (N = 66) of 140 relatives of 30 depressed patients. Family history of mental illness was ascertained by the informant method on the remainder of relatives of both proband groups. The rate of depression found in the relatives of schizotypal patients was 52% in those directly interviewed and 25.7% when informants' reports on unavailable relatives are pooled with direct interview data. These rates were not significantly higher than those found for the relatives of depressed probands (34.8% by direct interview and 21% including reports from informants). The high rates of depression in the relatives of schizotypal probands may indicate that schizotypal personality is associated with affective disorder and not only with schizophrenia. However, the high rates may be due to the presence of depressive character traits in relatives, which inflate the rates of dysthymic disorder and other chronic depressive disorders in the relatives of borderline patients.     

Lumbar disc syndrome in Finland.

The prevalence of lumbar disc syndrome (herniated disc or typical sciatica) and its consequences in terms of disability, handicap, and need for medical care were studied as part of the Mini-Finland Health Survey. A sample of 8000 persons representative of the Finnish population aged 30 or over was asked to come for examination, and 7217 (90%) participated. A diagnosis of lumbar disc syndrome based on medical history, symptoms, and standardised physical examination was made for 5.1% of the men and for 3.7% of the women. Half of these patients were assessed to be in need of medical care, over 80% of which was considered to be adequately met. One third of all patients with lumbar disc syndrome had been previously hospitalised for that syndrome, and one fifth of the patients had undergone lumbar surgery. At least slight disability was found in almost 60% of the patients, though severe functional limitations were rare. About 6% of the population's work disability was estimated to be attributable to lumbar disc syndrome.