Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation

BACKGROUND: Transforming growth factor (TGF)-beta1 is a profibrogenetic cytokine that has been implicated in the development of fibrosis in transplanted tissues. In this study, we have analyzed the genetic regulation of TGF-beta1 production in lung transplant recipients. METHOD: A polymerase chain reaction-single-stranded conformational polymorphism technique was used to detect polymorphisms in the TGF-beta1 gene from genomic DNA. Polymorphisms were shown to correlate with in vitro TGF-beta1 production by stimulated lymphocytes. A single-specific oligonucleotide probe hybridization method was devised to screen for these polymorphisms in lung transplant groups and controls. RESULTS: We have identified five polymorphisms in the TGF-beta1 gene: two in the promoter region at positions -800 and -509, one at position +72 in a nontranslated region, and two in the signal sequence at positions +869 and +915. The polymorphism at position +915 in the signal sequence, which changes codon 25 (arginine-->proline), is associated with interindividual variation in levels of TGF-beta1 production. Stimulated lymphocytes of homozygous genotype (arginine/arginine) from control individuals produced significantly more TGF-beta1 in vitro (10037+/-745 pg/ml) compared with heterozygous (arginine/proline) individuals (6729+/-883 pg/ml; P<0.02). In patients requiring lung transplantation for a fibrotic lung condition, there was an increase in the frequency of the high-producer TGF-beta1 allele (arginine). This allele was significantly associated with pretransplant fibrotic pathology (P<0.02) (n=45) when compared with controls (n=107) and with pretransplant nonfibrotic pathology (P<0.004) (n=50). This allele was also associated with allograft fibrosis in transbronchial biopsies when compared with controls (P<0.03) and with nonallograft fibrosis (P<0.01). CONCLUSION: The production of TGF-beta1 is under genetic control, and this in turn influences the development of lung fibrosis. Hence, the TGF-beta1 genotype has prognostic significance in transplant recipients.     

Anphen and energy status of the animal body

Energy status of rats was altered after administration of anphen [2,4-(hydroxy-3,5-ditretbutyl phenyl)-2-aminomalonic acid] at a dose of 40 mg/kg. Within 30 min after administration, maximal rates of NAD-dependent substrates and succinate oxidation were detected in liver mitochondria, which appears to occur due to activation of the mitochondrogenesis. The rate of electron transport in respiratory chain of mitochondria was decreased 1.3-1.6-fold within 1-1.5 hr, whereas within 3 hrs the patterns of oxidation and energetic coupling in liver mitochondria were reduced to control values. The similar alterations were observed in activities of lymphocyte alpha-glycerophosphate- and succinate dehydrogenases. Shifts in the pool of lipid peroxidation products in biological membranes was apparently responsible for alterations in activity of the energy metabolizing enzymes in lymphocytes and liver mitochondria.     

Health status of persons with acute radiation sickness caused by Chernobyl AES accident

Chemical prophylaxis is known to reduce the venographic prevalence of deep-vein thrombosis (DVT) after total knee replacement (TKR), but it is uncertain whether this affects the incidence of symptoms. Further analysis depends on the basic epidemiology of thromboembolic symptoms. We therefore studied the pattern of such symptoms in a consecutive series of 1000 patients with primary TKR, with particular reference to risk factors and prophylaxis. We reviewed all the clinical records and contacted all the patients individually, noting risk factors, prophylaxis, symptomatic pulmonary embolus (PE) or DVT and its timing, death and its causes, and all complications. All the patients wore antiembolism stockings, 83% had regional anaesthesia and 33.9% had chemical prophylaxis. One patient died from PE on the day of surgery, having had no prophylaxis giving a rate of 0.1% (95% CI 0.003% to 0.56%). Symptomatic, radiologically confirmed thromboembolism (VTE) was common with a rate of 10.6% (95% CI 8.7% to 12.5%). There was a similar incidence of VTE in those with and without chemical prophylaxis (10.1% v 10.5%, RR 0.96, NS). VTE was more common in patients with risk factors (15.1% v 9.5%, RR 1.59, p = 0.02) and tended to occur earlier in this group (median day of onset 5 v 7, p = 0.01). Chemical prophylaxis did not reduce the frequency of symptomatic thromboembolism in either those with risk factors (RR 0.81, p = 0.5) or those without them (RR 0.94, p = 0.8). Haematoma or wound dehiscence was more common in those having chemical prophylaxis (11.9% v 6.9%; RR 1.73 95% CI 1.16 to 2.60). Readmission for symptomatic, radio-logically confirmed thromboembolism involved 1.1% of patients (95% CI 0.55% to 2.1%). Four patients were readmitted with proven non-fatal PE and six with proven DVT (the latest on day 40). Our results show that the main risk factor for thromboembolism was TKR itself; chemical prophylaxis did not reduce the incidence of symptomatic thromboembolism but gave an increased perception of side-effects. New prophylactic methods or combinations of methods are needed, with their efficacy compared by randomised controlled studies of both the clinical and the radiological effect.     

Scientific information of health personnel: an approach to the sources, access, costs and research

OBJECTIVE: To study the appropriateness of minimally invasive surgical treatment of primary hyperparathyroidism. DESIGN: Prospective. SETTING: University Hospital Utrecht, the Netherlands. METHOD: In patients with primary hyperparathyroidism, parathyroid adenomas were located preoperatively by means of Doppler assisted ultrasonography and spiral computer tomography. If the results were positive, minimally invasive surgery was performed. RESULTS: Minimally invasive surgery was carried out in 13 out of 15 successive patients with good results (the serum calcium and parathyroid hormone levels returned to normal). Two patients were subjected to conventional neck exploration, also with good results (preoperatively several adenomas were suspected in one, while no adenoma was seen in the other). CONCLUSION: It can be calculated that minimally invasive surgery will probably suffice in 60-70% of the patients with primary hyperparathyroidism, so that conventional neck exploration can be avoided.     

The measurement of light scattering and electrical conductivity for the prediction of PSE pig meat at various times post mortem

Measurements of light scattering and electrical conductivity were made in the Longissimus dorsi (LD) and Semimembranosus (SM) muscles using the Fibre Optic Probe (FOP) and Quality Meter (QM), respectively, to assess their ability to estimate pig meat quality, particularly the occurrence of PSE meat. One-hundred-and-fifty-three gilt carcasses were measured on three occasions post mortem (pm): 45 min (FOP(45) and QM(45)), 2h (FOP(2) and QM(2) and 24 h (FOP(u) and QM(u)). Measurements of pH were taken in the same anatomical position and at the same times. At 24 h pm muscle reflectance (GOFO value) and subjective colour assessments were made on the cut surface of the LD at the level of the last rib. Water-holding capacity (WHC) was estimated in a sample taken from the exposed surface of the LD by the solubility of sarcoplasmic and myofibrillar proteins. The FOP(45) predicted most accurately the WHC (R(2) = 0·49). Neither of the other quality measurements improved the prediction at 45 min pm. However, at 2h, adding QM(2) as a second independent variable improved prediction of WHC (R(2) = 0.58). At 24 h the combination of FOPu, QMu and GOFO did not improve the prediction of WHC (R(2) = 0.58). The best prediction used measurements of FOP(45), QM(2) and GOFO (R(2) = 0·62). The best relationship between subjective colour scores and the quantitative measurements of meat quality using discriminant analysis was obtained with the FOPu with an error-count estimate of 15·1% followed by FOP(2) (17%), GOFO value (18·7%), pH(2) (19·7%) and QMu (20·2%). With combination measurements of two instruments, pH(2) and FOP(2) had the lowest error-count estimate (10·9%). No further precision was obtained with combinations of three instruments. These results suggest that FOP and QM can be used to predict PSE and normal pig meat at different times pm and can replace traditional pH muscle measurements.     

Die Bedeutung subjektiver Krankheitsvorstellungen in der Gesundheitsversorgung am Beispiel von Menschen mit (türkischem) Migrationshintergrund

Definition of the problem

People with a Turkish migration background are one of the largest population groups with migration background in Germany. Compared to the autochthonous population, they have a higher prevalence of certain chronic diseases, which is partly due to a low socioeconomic status. In addition, they encounter different barriers in the health system with respect to access and effectiveness of health care. These barriers result from needs and expectations of patients which are not sufficiently considered by health care institutions. This lack of patient-oriented health care may affect therapy and appropriate disease management, particularly in chronically ill individuals.

Conclusion

In order to provide patient-oriented health care, patients’ illness perceptions also need to be considered. For this purpose, health care providers must be made aware of their patients’ diverse beliefs. On the patients’ side, illness perceptions which support coping with an illness need to be supported. Simultaneously, patients should be empowered to critically reflect on their own perceptions that affect adequate coping with illness. This can be facilitated by means of interventions such as storytelling, which is based on the exchange of knowledge and experiences.

     

Low‐Bandgap Methylammonium‐Rubidium Cation Sn‐Rich Perovskites for Efficient Ultraviolet–Visible–Near Infrared Photodetectors

Solution‐processed and low‐temperature Sn‐rich perovskites show their low bandgap of about 1.2 eV, enabling potential applications in next‐generation cost‐effective ultraviolet (UV)–visible (vis)–near infrared (NIR) photodetection. Particularly, the crystallization (crystallinity and orientation) and film (smooth and dense film) properties of Sn‐rich perovskites are critical for efficient photodetectors, but are limitedly studied. Here, controllable crystallization for growing high‐quality films with the improvements of increased crystallinity and strengthened preferred orientation through a introducing rubidium cation into the methylammonium Sn‐Pb perovskite system (65% Sn) is achieved. Fundamentally, the theoretical results show that rubidium incorporation causes lower surface energy of (110) plane, facilitating growth in the dominating plane and suppressing growth of other competing planes. Consequently, the methylammonium‐rubidium Sn‐Pb perovskite photodetectors simultaneously achieve larger photocurrent and lower noise current. Finally, highly efficient UV–vis–NIR (300–1100 nm) photodetectors with record‐high linear dynamic range of 110 and 3 dB cut‐off frequency reaching 1 MHz are demonstrated. This work contributes to enriching the cation selection in Sn‐Pb perovskite systems and offering a promising candidate for low‐cost UV–vis–NIR photodetection.