Smoking and hypertension: risk factors for carotid stenosis

Summary The prevalence of smoking, hypertension and diabetes mellitus was assessed in 221 patients suffering from internal carotid stenosis and compared with the prevalences in two sex- and age-matched control groups composed of subjects having normal Doppler findings and from non-neurological outpatients. Of the subjects with carotid stenosis 27.6% were hypertensive smokers in comparison with 9.5% and 17.2% in the two control groups. The difference of the stenosis cohort from the two control groups was significant (P<0.01 and P=0.016 respectively). There was no statistically significant differences between the occurrence of diabetes and hypertension in non-smokers and patients who smoked. In 394 investigated patients suffering from carotid stenosis or occlusion an obstruction index, based on the Doppler shift frequency, was calculated. This index was lowest in the normotentive non-smokers. It was only insignificantly higher in the hypertensive non-smokers but significantly so in the normotensive smokers. The index was highest in the hypertensive non-smokers. It was concluded that cigarette smoking, especially if associated with hypertension, is a determinant risk factor for carotid stenosis and occlusion.     

Postnatal developmental changes in the responses of mouse primary vestibular neurons to externally applied galvanic currents.

The ontogenesis of vestibular primary neuron sensitivity to depolarisation produced by galvanic current stimulations was studied in mouse inner ear explants maintained in vitro. Cathodal galvanic stimulations, which elicit an increase of the discharge frequencies, are assumed to act on the spike initiation site by depolarizing the neuron. The responses of neurons to galvanic currents at various developmental stages were recorded. The pattern of responses reflected the sensitivities of the neurons to depolarization. At birth, about 75% of the vestibular neurons responded weakly to high intensity galvanic currents thus indicating that they were able to generate action potentials. However, the very low gain of the response to the stimulation revealed the immaturity of the neurons at the spike generation site. Between the day of birth and the ninth postnatal day, an increase in the gain of the responses was observed, indicating the enhancement of the sensitivity of the vestibular neurons to the galvanic currents. This increase in sensitivity was more pronounced from the fourth postnatal day. The response of the neurons to galvanic stimulation increased gradually during postnatal development without reaching a plateau at postnatal day 9 indicating that a further physiological maturation occurs after this stage. These results are consistent with the morphological maturation of the vestibular primary afferents and with previous studies showing that the physiological maturation parallels myelination of the afferent fibers.     

Decreased hyperthermic effect of MK-801 in selectively bred hypercholinergic rats

The Flinders Sensitive Line (FSL) of rats has been selectively bred to have increased sensitivity to cholinergic agonists. However, these rats exhibit altered responsiveness to a number of noncholinergic agents, such as apomorphine, buspirone and ethanol. This study compared the FSL and control Flinders Resistant Line (FRL) rats in terms of their hyperthermic response to the phencyclidine (PCP) receptor agonist, MK-801 (0.2 mg/kg SC) and their MK-801 binding characteristics. We have found that FSL rats react with a delayed hyperthermia, having a significantly lower hyperthermia for the first 120 min of observation. Thereafter the response does not differ in FSL and FRL rats. Both groups had similar affinities and numbers of [3H]MK-801 binding sites in the hippocampus/cerebral cortex. Pretreatment with scopolamine (1 mg/kg SC) failed to affect MK-801-induced hyperthermia in either line of rats. These findings suggest that selective breeding of FSL rats attenuated the secondary mechanisms involved in the PCP receptor-mediated hyperthermic response. However, by itself cholinergic supersensitivity does not appear to be a major factor in the blunted responsiveness of FSL rats to MK-801.     

Carcinoembryonic antigen expression of resurgent human colon carcinoma after treatment with therapeutic doses of 90Y-alpha-carcinoembryonic antigen monoclonal antibody

We have previously shown that the colon carcinoma (LS174T) xenografts that emerged shortly after radioimmunotherapy with 90Y-labeled anti-CEA monoclonal antibody (MAb) ZCE025 lacked significant expression of CEA in comparison with the untreated tumors. The present study was designed to establish if the immunophenotype of the treated tumors was the result of CEA specific therapy and if the effect was permanent. Athymic mice bearing LS174T tumors were treated either with 120 mu Ci of 90Y-ZCE025, an equal dose of 90Y-96.5 (nonspecific MAb), or received no treatment. When the treated tumors grew to approximately 1.5 cm in diameter (6 weeks after therapy), they were resected and aliquoted to be transplanted to other mice, plated in tissue culture, fixed in formalin, and homogenized for CEA quantitation. The procedure was repeated 3 times (a total of 4 months after treatment). The CEA content was evaluated 2 and 6 weeks after therapy and when the tumors were transplanted. We confirmed a 4-fold decrease of CEA in the resurgent tumors 6 weeks after specific 90Y-ZCE025 therapy, which was twice the decrease experienced by the tumors treated with nonspecific 90Y-96.5, indicating substantial and specific killing of CEA-expressing cells. The CEA content slowly but progressively increased with each new pass of the tumor in the mice, reaching approximately one-half the value of the controls at the end of the study. The resurgent tumors were also studied by immunohistochemistry with MAbs detecting different epitopes of CEA, keratin, TAG-72, and epithelial membrane antigen to evaluate possible additional immunophenotypic changes induced by radioimmunotherapy. Only the expression of TAG-72 (recognized by MAb B72.3) increased immediately after therapy, but it returned to the original levels by the end of the study. These results suggest that: (a) specific radioimmunotherapy with 90Y-ZCE025 selectively kills cells that express higher levels of CEA; (b) the immunophenotype of the surviving fraction of the tumor appears to slowly revert to its original form; and (c) other tumor markers unrelated to CEA can also be affected. These observations have important implications for the design of radioimmunotherapy trials.     

Bernardino Ramazzini (1633-1714). On the 275th anniversary of the death of the founder of occupational dermatology

Ramazzini is not only reputed to be the father of industrial hygiene, but must be thought to be the founder of occupational dermatology too. In his famous book about diseases of artists and craftsmen (De morbis artificium diatriba) he shows us numerous job-caused dermatoses, their occupational background, and makes proposals for their treatment and prophylaxis. The medical inspection of the work place and asking for the occupational history of the patient are tracing back to him too. His life is described.     

Electron microscopic immunocytochemical evidence for the existence of bidirectional synaptic connections between growth hormone-releasing hormone- and somatostatin-containing neurons in the hypothalamus of the rat

Synaptic contacts between growth hormone-releasing hormone (GHRH)- and somatostatin-containing neurons were demonstrated in the rat hypothalamus by a double-staining immunocytochemical method at the electron microscopic level. Somatostatin-immunoreactive nerve terminals synapse on GHRH-positive dendrites and cell bodies in the arcuate nucleus. A fine network of GHRH-immunopositive nerve terminals was observed at the light microscopic level in the rostral part of the periventricular nucleus and in the dorsal part of the arcuate nucleus around somatostatin-containing neuronal elements. With the electron microscope synaptic contact between GHRH-containing nerve terminals and somatostatin-containing dendrites are demonstrated. The reciprocal innervation between GHRH- and somatostatin-containing neurons that project to the median eminence and regulate growth hormone secretion must allow them to coordinate their activities.     

Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury

Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation.     

The factor of magnification in mammography

The last generation of mammographic equipment allows mammography to be performed with direct magnification techniques, thanks to such technical features as microfocus, high focus-film distance, high-power generators. The authors compared the diagnostic yield of two different equipment sets, with 1.4x and 2x magnification respectively, and verified the utility of magnification radiography. A significant reduction was obtained in questionable diagnoses (42 to 18) in a group of 63 patients, with no evidence of substantial differences in the diagnostic yield of the images obtained with different magnification ratios. An objective analysis of the system resolution power privileges 2x magnification ratio, which however implies an increase in the average dose to the breast. The use of faster recording systems reduces the dose by 50%, though maintaining good image quality.