Experiences with risk estimates for carriers of chromosomal reciprocal translocations

The risk estimates for individual carriers of ten different familial reciprocal translocations detected among 500 couples with reproductive failures are presented. These were established by application of the empirical data analysed by Stengel-Rutkowski et al. (1988) and the guidelines given in Stene & Stengel-Rutkowski (1988). Different risks were estimated for unbalanced offspring at birth or at second trimester prenatal diagnosis for abortions, or stillbirths/early deaths. These risk estimates varied considerably from translocation to translocation. Carriers of five translocations had risks for offspring with single-segment imbalances. The birth risk figures ranged from 0.1% to 13.8%. Carriers of five other translocations had risks for double-segment imbalances with birth risks ranging from 0% to 3.2%. The estimated risk figures were independent of the method of ascertainment. Among the parents of the index cases we found nine maternal carriers and only one paternal carrier. This presentation illustrates the need for individual risk counselling of each carrier with reciprocal translocation regarding further family planning.     

Intracortical inhibition and facilitation in paired-pulse transcranial magnetic stimulation: effect of conditioning stimulus intensity on sizes and latencies of motor evoked potentials.

The influence of the intensity of the conditioning stimulus on intracortical inhibition (ICI) and intracortical facilitation (ICF) was assessed in a study using paired-pulse transcranial magnetic stimulation. Interstimulus intervals (ISIs) between conditioning and test stimuli were 3 msec and 13 msec. Latencies and areas of motor evoked potentials in response to the test stimulus were measured in the right extensor carpi radialis muscle. Motor evoked potential areas with ISIs of 3 msec and 13 msec showed a different dependence on the intensity of the conditioning stimulus. In contrast, the changes of motor evoked potential latencies were fairly similar with both ISIs. The findings point to a parallel action of ICI and ICF. Furthermore, the latencies seem to be a more sensitive indicator for ICF action than the size parameters of motor evoked potentials.     

Induction of monocyte chemotaxis in devascularized rabbit bone

Summary Temporary impairment of blood supply has been suggested to cause bone remodeling. The degradation of cells and matrix and the attraction of resorbing cells were examined in this study. Bone specimens of rabbits were stored in vitro for 2–20 days. At the end of this aging process the probes were tested for their chemotactic activity toward autologous leukocytes in a diffusion chamber. Both supernatant from the aged bone specimens and ground bone particles exhibited significant chemotactic activity that was specifically attracting monocytes. It is suggested that soluble bone matrix proteins or degeneration products liberated during ischemic damage to cortical bone initiate the resorptive process.This work was supported by the Swiss National Science Foundation, grant no. 3.857.0.83, and by the Studienstiftung des deutschen Volkes     

Amplification of the c-erbB oncogene is associated with malignancy in primary tumours of neuroepithelial tissue

Summary In various primary brain tumours of neuroepithelial tissue recombinant DNA techniques were used to demonstrate changes of the epidermal growth factor receptor gene, which is homologous to the c-erbB oncogene. Twenty-one of 40 grade III/IV tumours, but only 1 of 16 grade I/II tumours were found to contain amplified and/or rearranged c-erbB sequences. This highly significant difference suggest that c-erbB amplification, rearrangement, or both, are important steps in malignant transformation in a subset of patients with neuroepithelial tumours.     

Fusion and failure following anterior cervical plating with dynamic or rigid plates: 6-months results of a multi-centric, prospective, randomized, controlled study

Anterior cervical plate fixation is an approved surgical technique for cervical spine stabilization in the presence of anterior cervical instability. Rigid plate design with screws rigidly locked to the plate is widely used and is thought to provide a better fixation for the treated spinal segment than a dynamic design in which the screws may slide when the graft is settling. Recent biomechanical studies showed that dynamic anterior plates provide a better graft loading possibly leading to accelerated spinal fusion with a lower incidence of implant complications. This, however, was investigated in vitro and does not necessarily mean to be the case in vivo, as well. Thus, the two major aspects of this study were to compare the speed of bone fusion and the rate of implant complications using either rigid- or dynamic plates. The study design is prospective, randomized, controlled, and multi-centric, having been approved by respective ethic committees of all participating sites. One hundred and thirty-two patients were included in this study and randomly assigned to one of the two groups, both undergoing routine level-1- or level-2 anterior cervical discectomy with autograft fusion receiving either a dynamic plate with screws being locked in ap - position (ABC, Aesculap, Germany), or a rigid plate (CSLP, Synthes, Switzerland). Segmental mobility and implant complications were compared after 3- and 6 months, respectively. All measurements were performed by an independent radiologist. Mobility results after 6 months were available for 77 patients (43 ABC/34 CSLP). Mean segmental mobility for the ABC group was 1.7 mm at the time of discharge, 1.4 mm after 3 months, and 0.8 mm after 6 months. For the CSLP- group the measurements were 1.0, 1.8, and 1.7 mm, respectively. The differences of mean segmental mobility were statistically significant between both groups after 6 months (P = 0.02). Four patients of the CSLP-group demonstrated surgical hardware complications, whereas no implant complications were observed within the ABC-group (P = 0.0375). Dynamic plate designs provided a faster fusion of the cervical spine compared with rigid plate designs after prior spinal surgery. Moreover, the rate of implant complications was lower within the group of patients receiving a dynamic plate. These interim results refer to a follow-up period of 6 months after prior spinal surgery. Further investigations will be performed 2 years postoperatively.     

The mechanism of yohimbine-induced renin release in the conscious rat

Summary These studies were designed to determine the role of the central nervous system, the sympathetic nervous system, the adrenal glands and the renal sympathetic nerves in yohimbine-induced renin release in conscious rats. Yohimbine (0.3–10 mg/kg, s.c.) caused time- and dose-related increases in plasma renin activity (PRA) and concentration (PRC) which were accompanied by time- and dose-related elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. Significant positive correlations were found between the increases in PRA and the increases in plasma NE and Epi concentrations caused by yohimbine, and propranolol (1.5 mg/kg, s.c.) blocked 90% of yohimbine (3 mg/kg, s.c.)-induced renin release. Over the entire spectrum of doses of yohimbine, the increases in PRA and plasma NE and Epi concentrations were positively correlated with the decreases in mean arterial pressure (MAP), but the -intercept was positive in every case and the 1 mg/ kg dose of yohimbine consistently increased PRA independent of any change in MAP. Complete renal denervation, as evidenced by a greater than 90% reduction in renal NE content, did not alter the increase in PRA caused by yohimbine (3 mg/kg, s.c.). An increase in circulating plasma catecholamine concentrations appeared to mediate yohimbine-induced renin release since propranolol prevented the rise in PRA caused by yohimbine in renal denervated rats. Prior adrenalectomy (Adx) also failed to prevent the rise in PRA produced by yohimbine (3 mg/kg, s.c.), but a combination of Adx and renal denervation caused a significant impairment of yohimbine-induced renin release. However, neither Adx alone nor the combination of Adx and renal denervation affected the increase in plasma NE concentration caused by yohimbine. Complete transection of the spinal cord at C₈ caused a drastic reduction in plasma catecholamine concentrations but did not change basal PRC. Yohimbine (3 mg/kg, s.c.) did not increase PRC or plasma catecholamine concentrations after spinal transection. Based on these results, we conclude that 1) the stimulation of renin release by yohimbine is a secondary neurohormonal consequence of the generalized increase in sympathetic activity caused by yohimbine, 2) the sympathoadrenal activation produced by yohimbine results from an action in the brain which is amplified by the simultaneous blockade of prejunctional ₂-adrenoceptors and 3) vasodepressor effects of the larger doses yohimbine cause a baroreflexly-mediated increase in sympathetic activity which interacts in a positive fashion with the central and peripheral sympathoexcitatory effects of yohimbine. Send offprint requests to T. K. Keeton     

Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be oxidized only after an initial oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me₂) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me₂) which cannot be oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1-¹⁴C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid, which indicated that all the methyl-branched iodo fatty acids underwent a strong deiodination process. Fatty acids were esterified in the following order: palmitic acid >16-iodo-3-R,S-methyl palmitic acid>16-iodo-2-R,S-methyl palmitic acid>16-iodo-2,2-dimethyl palmitic acid>16-iodo-3,3-dimethyl palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethylbranched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[¹²⁵I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1-¹⁴C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched-palmitic acids were found in hepatocyte or secred phospholipids as compared with palmitic acid. This metabolic fate of methyl-branched iodo palmitic acids argues against their utilization as imaging probes to monitor in vivo the synthesis and the secretion of triglycerides by the liver.     

Socioeconomic position and cardiovascular and neuroendocrine responses following cognitive challenge in old age

Social disparities in health persist into old age, and differences in psychophysiological responsivity may contribute to this pattern. We assessed whether higher socioeconomic status (SES) is associated with attenuated cardiovascular and neuroendocrine responses elicited by cognitive tasks in old age. We tested 132 community-dwelling men and women aged 65-80 years, divided on the basis of educational attainment into higher and lower SES groups, and compared them with 26 higher educated participants aged 27-42 years. Blood pressure, hemodynamic variables and salivary cortisol were assessed in response to the performance of three cognitive tasks, and then during recovery. Older groups showed smaller heart rate and larger cortisol changes than younger participants. Post-task recovery in heart rate, stroke volume, pre-ejection period, and systolic blood pressure was greatest in the younger group, least in the older/lower education group, and intermediate in the older/higher education group. SES did not influence the increased cortisol responsivity of older participants. The results are consistent with the notion that higher SES protects against age-related changes in cardiovascular response profiles, particularly during recovery.     

Investigations on the biology,epidemiology, pathology and control of<Emphasis Type="Italic"> Tunga penetrans</Emphasis> in Brazil: I. Natural history of tungiasis in man

Tungiasis is an important health problem in poor communities in Brazil and is associated with severe morbidity, particularly in children. The causative agent, the female flea Tunga penetrans, burrows into the skin of its host, where it develops, produces eggs and eventually dies. From the beginning of the penetration to the elimination of the carcass of the ectoparasite by skin repair mechanisms, the whole process takes 4-6 weeks. The present study is based on specimens from 86 patients, for some of whom the exact time of penetration was known. Lesions were photographed, described in detail and biopsied. Biopsies were examined histologically and by means of scanning electron microscopy (SEM). Based on clinical, SEM and histological findings, the "Fortaleza classification" was elaborated. This allows the natural history of tungiasis to be divided into five stages: (1) the penetration phase, (2) the phase of beginning hypertrophy, (3) the white halo phase, (4) the involution phase and (5) residues in the host's skin. Based on morphological and functional criteria, stages 3 and 4 are divided into further substages. The proposed Fortaleza classification can be used for clinical and epidemiological purposes. It allows a more precise diagnosis, enables the assessment of chemotherapeutic approaches and helps to evaluate control measures at the community level.