The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Total sleep deprivation decreases saliva ghrelin levels in adolescents

Ghrelin, a regulator of food intake and energy expenditure, has been shown to be associated with insufficient sleep. The goal of the present study was to investigate the effect of a single night of total sleep deprivation on fasting saliva ghrelin and on nocturnal variation of saliva ghrelin concentration. A further aim of the study was to investigate the influence of body mass index on changes in saliva ghrelin levels. Altogether 35 adolescents (18 boys; age: 13.8 ± 1.14 years) were studied on two subsequent days (sleep and total sleep deprivation). Saliva samples were collected during the two experimental nights at 21:00 hours, 01:00 hours and 06:00 hours. Total-ghrelin concentration showed a continuous increase from the evening until 06:00 hours. This increase was blunted significantly (p = 0.003) by total sleep deprivation. Total-ghrelin level was significantly lower (p = 0.02) during total sleep deprivation at 06:00 hours (median 403.6 pg ml⁻¹; 95% confidence interval: 343.1–468.9 pg ml⁻¹) as compared with values during the sleep condition (median 471.2 pg ml⁻¹; 95% confidence interval: 205.4–1578.7 pg ml⁻¹). Acyl-ghrelin levels did not present any change at the three time points, and were not affected by total sleep deprivation. Stratifying the study population according to body mass index (normal weight and overweight/obese groups), the blunting effect of total sleep deprivation was more pronounced in the obese/overweight group (sleep: median 428.2 pg ml⁻¹; 95% confidence interval: 331.3–606.9 pg ml⁻¹ versus total sleep deprivation: median 333.1 pg ml⁻¹; 95% confidence interval: 261.5–412.9 pg ml⁻¹; p = 0.0479). Saliva total-ghrelin concentrations gradually increased during the night, and total sleep deprivation significantly blunted this increase. This blunting effect was mainly observed in subjects with overweight/obesity. The physiological and clinical implications of the present observation are to be clarified by further studies.     

Gastrointestinal imaging: a systems analysis comparing digital and conventional techniques

OBJECTIVE: The purpose of this study was to compare digital and conventional methods of gastrointestinal imaging based on the cost of image storage and estimated overall costs, radiation exposure to the patient, and duration of the examination. MATERIALS AND METHODS: Our study sample consisted of 128 patients who underwent conventional gastrointestinal studies (64 double-contrast upper gastrointestinal examinations and 64 double-contrast barium enemas) and 139 patients who underwent digital gastrointestinal studies (66 double-contrast upper gastrointestinal examinations and 73 double-contrast barium enemas). The number of images and films for each study was recorded, and the mean cost of image storage and the estimated overall costs for digital versus conventional studies were calculated. Both the duration of fluoroscopy and the time from start to completion of the study were obtained from our radiology information system. From these data, we calculated mean radiation exposure to the patient and the duration of the examination. Finally, referring physicians completed a questionnaire about their level of satisfaction with paper prints generated from digital gastrointestinal studies. RESULTS: When digital studies were compared with conventional studies, the mean cost of image storage decreased by 45% and the estimated overall 10-year costs decreased by 8%. The mean number of spot images increased by 8% for upper gastrointestinal examinations and by 25% for barium enema examinations, whereas the mean duration of fluoroscopy decreased by 4% and by 10%, respectively. As a result, radiation exposure to patients increased by only 2%, a difference that did not approach statistical significance. Finally, the mean duration of examinations decreased by 24% for upper gastrointestinal examinations and by 33% for barium enemas. Approximately 85% of the physicians who completed the questionnaires indicated that they reviewed the paper prints generated from digital studies and that they would like to continue receiving them. CONCLUSION: Digital gastrointestinal imaging systems are associated with higher initial costs than conventional systems, but the long-term costs of these digital imaging systems are slightly less because of the lower cost of image storage, and radiation exposure to patients is comparable. The shorter duration of digital examinations is a potential benefit of this technology, allowing improved patient throughput. Finally, referring physicians have a high level of satisfaction with paper prints generated from digital imaging.     

Impact of retrograde cerebral perfusion on aortic arch aneurysm repair

OBJECTIVE: Protection of the brain is a primary concern in aortic arch surgery. Retrograde cerebral perfusion is a relatively new technique used for cerebral protection during profound hypothermic circulatory arrest. This study was designed to compare, retrospectively, the outcome of 109 patients undergoing aortic arch operation with and without the use of retrograde cerebral perfusion. METHODS: Fifty-five patients had profound hypothermic circulatory arrest alone, and 54 patients had supplemental cerebral protection with retrograde cerebral perfusion. Mean age was 61 +/- 13 years and 58 +/- 14 years, respectively (mean +/- standard deviation). Twenty-two preoperative and intraoperative characteristics, including age, sex, acuity, presence of aortic dissection, and aneurysm rupture, were similar in the 2 groups (P >.05). RESULTS: Mean circulatory arrest times (in minutes) were 30 +/- 19 in the group without retrograde cerebral perfusion and 33 +/- 19 in the group with retrograde cerebral perfusion, respectively. chi(2) Analysis revealed that patients operated on with the use of retrograde cerebral perfusion had significantly lower hospital mortality (15% vs 31%; P =.04) and in-hospital permanent neurologic complications (9% vs 27%; P =.01). Retrograde cerebral perfusion failed to reduce the prevalence of temporary neurologic dysfunction (17% vs 18%; P =.9). Stepwise multiple logistic regression revealed that extracorporeal circulation time, age, and lack of retrograde cerebral perfusion were statistically significant independent risk factors for hospital mortality. The same analysis revealed that lack of retrograde cerebral perfusion was the only significant independent risk factor for permanent neurologic dysfunction. CONCLUSION: Retrograde cerebral perfusion decreased the prevalence of permanent neurologic complications and the hospital mortality in patients undergoing aortic arch operations.     

3H-spiperone binding to lymphocytes in neuroleptic-naive-schizophrenia and the effect of neuroleptic treatment

The aim of this study was to determine whether spiperone binding to lymphocytes could serve as a biological marker of susceptibility to schizophrenia and schizophrenic spectrum disorders or as a measure of response to neuroleptic treatment. Lymphocyte spiperone binding parameters (Bmax, KD) were assessed in 13 patients with schizophrenia and 4 patients with schizotypal personality disorder, all neuroleptic naive, and in 19 age- and sex-matched control subjects. A repeated determination was carried out in 11 of the schizophrenic subjects after several months of neuroleptic treatment. In addition, the binding characteristics of 12 of the schizophrenic/schizotypal patients were compared with those of 13 healthy family members and normal unrelated controls. No significant differences were detected between the schizophrenic subjects and controls before or after neuroleptic treatment or between the patients and their non-affected family members and controls.     

Hemin enhances the in vitro growth of primitive erythroid progenitor cells

Since exogenous hemin has been shown to exert a variety of stimulatory effects on erythroid cells, including the augmentation of hemoglobin synthesis, we determined its effect on early stages of erythroid development by employing clonal cells assays. The addition of hemin at a concentration of 2 X 10(-4) M to cultures of normal murine marrow substantially increased the observed number of primitive BFU-E, which was in contrast to its lack of an effect on more mature erythroid colony-forming cells. This cell-specific enhancement of primitive BFU-E resulted in marrow frequencies equivalent to or exceeding those reported in the presence of "burst-promoting activity." In the presence of hemin, the number of BFU-E was also observed to be linearly related to the number of cells plated at very low plating densities, and the cell titration curve was observed to extrapolate to the origin. The evidence suggests that hemin may be a primary growth regulator of early developmental stages of erythroid progenitor cells.     

Osijek Health Center during the 1991-1992 war in Croatia

To assess the effectiveness of health services in the city of Osijek during the 1991-1992 war in Croatia, we followed the changes in the utilization of health services, morbidity and mortality, and completion of a vaccination plan during the 2 years of the war. We used a retrospective analysis of data from the Osijek Health Center and the Osijek County Institute of Public Health. The organization of health care during the war followed the concept of integrated health care and the instructions of the Ministry of Health. Visits to primary health care physicians decreased considerably, with a concomitant increase in disease and mortality. The plan for mandatory vaccination was not completed because of the evacuation of preschool and school children. The war changed the mode of health care use, the disease and mortality structure, and the implementation of mandatory vaccination. However, timely education and preparation of the health services to the war situation resulted in an adequate provision of health care to the population.     

Improved long-term results with thymoglobuline induction therapy after cardiac transplantation: a comparison of two different rabbit-antithymocyte globulines

BACKGROUND: The aim of this retrospective single center analysis was to compare possible long-term benefits of two different rabbit-antithymocyte globuline (ATG) induction therapies after cardiac transplantation. PATIENTS AND METHODS: A total of 484 primary cardiac transplanted patients received induction therapy with two different rabbit-ATGs (thymoglobuline: n=342, ATG-fresenius: n=142). All patients received immunosuppressive maintenance therapy with cyclosporine, azathioprine, and prednisolone. Cardiac rejection was assessed by serial endomyocardial biopsies. Surveillance of graft arteriosclerosis was performed by angiograms 1, 3, and 5 years after transplantation. RESULTS: Five-year survival was significantly better in the thymoglobuline group (76 vs. 60%). Thymoglobuline patients had a lower rate of death from rejection (2.3 vs. 10%; P<0.01) and graft arteriosclerosis (0.88 vs. 5.6%; P<0.01). After 5 years, freedom from rejection was 72% in the thymoglobuline group compared to 42% in the ATG-fresenius group (P<0.01). Graft arteriosclerosis appeared in 14% of thymoglobuline patients and in 28% of ATG-fresenius patients (P<0.01). Viral infections occurred more often in thymoglobuline patients (53 vs. 39%, P<0.05) although there was no difference in appearance of cytomegalovirus disease (17 vs. 13%). Freedom from posttransplant malignant disease was comparable between the two groups. CONCLUSION: These results suggest that there are differences between rabbit ATG products. The superior prevention of rejection with thymoglobuline may be the reason for the lower rate of graft arteriosclerosis.