Human mini-chromosomes in mouse embryonal stem cells

We have introduced human mini-chromosomes of 4 Mb and approximately 15 Mb in size into mouse embryonal stem cells. Although these human mini- chromosomes are stable in hamster and chicken cells, they re-arrange or segregate aberrantly in the embryonal stem cells and are rapidly lost in the absence of selection. However, one of the mini-chromosomes re- arranged, acquired mouse centromeric sequences and was then stably maintained for at least 60 population doublings in culture. This mini- chromosome, which is 4 Mb in size, is a candidate for a mouse germ line chromosome vector.      

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes

PurposeDissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.Materials and MethodsA total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).ResultsThe cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.ConclusionThe presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; {"type":"clinical-trial","attrs":{"text":"NCT04619277","term_id":"NCT04619277"}}NCT04619277).     

Juvenile dermatomyositis associated with autoantibodies to small ubiquitin-like modifier activating enzyme: a report of 4 cases from North India and a review of literature

Immunologic Research - Juvenile dermatomyositis (JDM) is the commonest inflammatory myositis in children. The clinical phenotype is often characterized by the presence of myositis-specific...     

Epidemiology of early neonatal mortality

During 1981-1991 at a rural teaching hospital (Kasturba Hospital) of Mahatma Gandhi Institute of Medical Sciences in Sevagram, Wardha, India, 454 of 13,939 newborns died during the early neonatal period for an early neonatal mortality rate (ENMR) of 33.7/1000 live births. The ENMR for boys was not significantly different from that for girls (36.1 vs. 28.6). Community medicine specialists analyzed data on these early neonatal deaths to examine distribution of early neonatal mortality, especially its relationship with prematurity, low birth weight, birth order, and by sex. They calculated average percent deaths (APD) per hour to examine the dynamics in early neonatal mortality. The mean age at death was lower among newborns of birth order greater than 2 than those of birth order less than 2 (23.47 vs. 26.85 hours; p 0.001). ENMR was higher for newborns of birth order greater than 2 than those of birth order less than 2 (41.74% vs. 27.35%; P 0.001). The mean age at death increased as gestation increased (10.34 for 28 weeks; 24.27 for 28-33 weeks, 31.53 for 33-37 weeks, and 34.43 for 37 weeks; p 0.001). ENMR decreased as gestation increased (850 for 28 weeks; 375 for 28-33 weeks, 147.02 for 33-37 weeks, and 8.77 for 37 weeks; p 0.001). The mean age at death increased as birth weight increased for newborns weighing less than 1500 gms through 2000-2500 gms (23.36-37.13 hours; p 0.001). It was lowest among those weighing more 3000 gms (11.55 gms). ENMR fell as birth weight increased (614.33 for 1500 gms, 116.19 for 1500-2000 gms, 19.38 for 2000-2500 gms, 10.99 for 2500-3000 gms, and 5.41 for 3000 gms; p 0.001). The APD/hour for the first hour of life was 3.74% for a relative risk of 12.9. It decreased steadily as the hours of life increased (3.08% for 1-6 hours, 1.19% for 6-24 hours, 0.67% for 24-72 hours, and 0.29% for 72-168 hours). Knowledge of time of likely death can help providers know where they need to focus their attention to prevent early neonatal deaths.     

Effects of Acute and Chronic Inflammation on the Pharmacokinetics of Prednisolone in Rats

The effects of acute and chronic stages of carrageenan-induced air-pouch inflammation on the pharmacokinetics of prednisolone were studied in male Wistar rats. Chronic inflammation produced a significant increase in the area under the curve (AUC) of prednisolone compared to control animals (6594 ± 2144 vs 3530 ± 2164 µg · hr/ L). The effect of acute inflammation was not significant (AUC = 4996 ± 3813). Both acute and chronic inflammation also reduced thein vitro plasma protein binding of prednisolone, the reduction being much greater after chronic inflammation. The AUC of free prednisolone after chronic inflammation was 3141 µg · hr/L, compared to 1121 µg · hr/L in the control group and 1823 µg · hr/L after acute inflammation. The mean values of half-life and apparent volume of distribution at steady-state in each group were similar. These results indicate that prednisolone must be used with caution in the treatment of inflammatory diseases because of higher free concentrations of the steroid.     

Effect of the ownership of dialysis facilities on patients' survival and referral for transplantation

BACKGROUND: More than 200,000 patients with end-stage renal disease undergo dialysis in the United States each year, about two thirds in for-profit centers. Economic pressures, such as the decline in inflation-adjusted Medicare payments for dialysis, may compromise the quality of care. Facilities may also be reluctant to refer patients to be evaluated for transplantation because of the loss of revenues from dialysis after patients receive transplants. It is unknown whether for-profit facilities respond more aggressively than not-for-profit facilities to these financial pressures. Therefore, we examined the effect of for-profit ownership of dialysis facilities on patients' survival and referral for possible transplantation. METHODS: We used data from the U.S. Renal Data System to assemble a nationally representative cohort of patients with end-stage renal disease of recent onset. We followed patients for a minimum of three years and a maximum of six years, until death, placement on the waiting list for a renal transplant, or loss to follow-up, or until May 31, 1996. We used proportional-hazards models to assess the effect of the profit status of the dialysis facility on patients' outcomes and adjusted for differences in sociodemographic, clinical, and facility-level characteristics. RESULTS: Of the 3681 patients who were eligible for inclusion, we included 3569 in the analysis of mortality and 3441 in the analysis of the waiting list. The crude mortality rate per 100 person-years of end-stage renal disease was 21.2 for patients treated in for-profit facilities and 17.1 for patients treated in not-for-profit centers (adjusted relative hazard, 1.20; 95 percent confidence interval, 1.02 to 1.42). The likelihood of being placed on the waiting list for a renal transplant was lower for patients treated at for-profit centers (adjusted relative hazard, 0.74; 95 percent confidence interval, 0.56 to 0.98). CONCLUSIONS: In the United States, for-profit ownership of dialysis facilities, as compared with not-for-profit ownership, is associated with increased mortality and decreased rates of placement on the waiting list for a renal transplant.     

Half-ring external fixation in the management of tibial plafond fractures

OBJECTIVE: To investigate the management of tibial plafond fractures with a half-ring external fixator using half pins. DESIGN: Prospective. SETTING: University teaching hospital. PATIENTS: Twenty-four patients with AO Type A or C tibial plafond fractures. OUTCOME MEASURES: Outcome was assessed by using standard criteria of time to union, incidence of infection and malunion, and incidence of pin-tract sepsis. Functional return was assessed by measuring hindfoot function. A scoring system, incorporating clinical and radiological results, was used to rate the results. RESULTS: When using closed or minimally open reduction techniques and interfragmentary screw fixation for the articular component of the fractures, the results of using a half-ring external fixator with half-pins were comparable with those of using small wire fixators. There was a 4.2 percent incidence of infection, and 75 percent of the patients had good or excellent results. CONCLUSIONS: A half-ring external fixator using half-pins produces results that are comparable to those obtained with small wire external fixation. However, the technique is easier and safer.