Effect of dietary restriction upon the age-associated decline of lymphocyte DNA repair activity in mice

Effects of dietary restriction (DR) on DNA repair capacity of mouse splenocytes after ultraviolet (UV)-induced damage were assessed. Two mouse cohorts received restricted amounts of purified hypocaloric diets; one was minimally restricted (∼75% of the caloric intake of mice fed a commercial diet ad libitum), the other was severely restricted (∼50% caloric restriction). An inverse correlation between age and DNA repair was present in the two cohorts; however, the regression lines of the two cohorts showed different slopes. DR appears to decelerate the age-associated decline of DNA repair capacity, and this delay might account in part for the improved immune function shown by old mice on DR.     

Proliferative and cytotoxic immune functions in ageing mice. I. Sequence of decline of reactivities measured under optimal and suboptimal sensitization conditions.

Individual young adult, middle-aged, and old C57BL/6J male mice were tested for in vitro generated proliferative and cytotoxic responses to H-2 alloantigens under a variety of sensitization conditions. Proliferation in mixed lymphocyte culture (MLC) had decreased by 14 months of age (middle-aged), whether measured by directly assaying cultures in microtitre plates (micro MLC) or by labelling aliquots taken from large culture tubes (macro MLC). Cytotoxicity did not decline until a later age if sensitization was done in large tubes (macro cell-mediated lympholysis, CML). When cytotoxic activity was assayed by measuring lysis after addition of chromated cells to MLCs in microtitre plates (micro CML), differences were revealed between young and middle-aged animals. However, these conditions were suboptimal for generation of cytotoxicity even in young controls and showed even lower responses in the middle-aged group. It was concluded that proliferation showed an earlier, more severe decline than cytotoxicity with age as the proliferative response had declined by middle-age under all sensitization conditions used. With optimal sensitization conditions, senescent mice (26--30 months) showed a four- to ten-fold decrease in cytotoxicity compared with young adult mice.     

Free insulin levels and metabolic effects of meal-time bolus and square-wave intraperitoneal insulin infusion in insulin-dependent diabetic patients

Summary The intraperitoneal route may offer more physiological insulin delivery through absorption of a proportion of the dose into the portal circulation. We have compared 1-h square-wave and bolus supplemental infusions of a fixed dose of 10 U of intraperitoneal insulin in 6 C-peptide negative insulin-dependent diabetic patients eating a standard breakfast and compared the insulin, glucose and metabolite responses with those of non-diabetic control subjects. Blood glucose profiles were similar on the two experimental days and although the peak glucose levels were not different from normal they were delayed by 30 min (p<0.05). Basal free insulin levels were elevated in diabetic patients (square-wave 19.6±2.3, bolus 18.7±1.9mU/l) compared to controls (7.3±1.0mU/l, p< 0.02) and rose more rapidly after bolus injection than infusion. Peak insulin concentration was achieved at 33±4 min after bolus, 90±13 min after infusion (p<0.02) and 39±5 min in normal control subjects. The shape of the profile of free insulin concentration was similar after bolus injection and in the controls, but after square-wave infusion the return to baseline was delayed (p< 0.05). Fasting intermediary metabolite concentrations were normal on both study days in the patients, but serum cortisol levels were significantly elevated and glucagon concentrations low. Metabolite responses to the meal were not significantly different from normal after bolus injection but increases in lactate and glycerol were seen at some time points between 60 and 180 min after infusion. Glucagon levels remained low after square-wave infusion. We conclude that bolus injection of the breakfast insulin supplement gives a more optimal profile of insulin delivery for patients on intraperitoneal insulin.     

The New York State cardiac registries: history, contributions, limitations, and lessons for future efforts to assess and publicly report healthcare outcomes

In 1988, the New York State Health Commissioner was confronted with hospital-level data demonstrating very large, multiple-year, interhospital variations in short-term mortality and complications for cardiac surgery. The concern with the extent to which these differences were due to variations in patients' pre-surgical severity of illness versus hospitals' quality of care led to the development of clinical registries for cardiac surgery in 1989 and for percutaneous coronary interventions in 1992 in New York. In 1990, the Department of Health released hospitals' risk-adjusted cardiac surgery mortality rates for the first time, and shortly thereafter, similar data were released for hospitals and physicians for percutaneous coronary interventions, cardiac valve surgery, and pediatric cardiac surgery (only hospital data). This practice is still ongoing. The purpose of this communication is to relate the history of this initiative, including changes or purported changes that have occurred since the public release of cardiac data. These changes include decreases in risk-adjusted mortality, cessation of cardiac surgery in New York by low-volume and high-mortality surgeons, out-of-state referral or avoidance of cardiac surgery/angioplasty for high-risk patients, alteration of contracting choices by insurance companies, and modifications in market share of cardiac hospitals. Evidence related to these impacts is reviewed and critiqued. This communication also includes a summary of numerous studies that used New York's cardiac registries to examine a variety of policy issues regarding the choice and use of cardiac procedures, the comparative effectiveness of competing treatment options, and the examination of the relationship among processes, structures, and outcomes of cardiac care.     

Double vs single balloon technique for aortic balloon valvuloplasty

Percutaneous aortic valvuloplasty using a single dilating balloon has been associated with significant but modest reduction in transvalvular pressure gradient and increase in valve area. The balloon diameter is usually 20 mm or smaller to avoid disruption of aortic root structure and to permit forward blood flow during inflation. To evaluate the safety and efficacy of valvuloplasty using a combination of balloons with larger maximum inflated diameters, we compared results of aortic valvuloplasty in 21 patients using either the single or double balloon technique. Mean maximum inflated balloon diameter was 19.4 mm +/- 1.4 for the single balloon technique, while the mean sum of diameters for the simultaneous double balloon technique was 36.3 mm +/- 3.9. The mean age, aortic annulus diameter, and predilatation aortic valve area were not different among groups. Mean aortic transvalvular gradient reduction and mean aortic valve area increase were greater for the double balloon technique. The procedure was well tolerated with no major complications. No change in the degree of aortic regurgitation was noted. The double balloon technique for aortic valvuloplasty is safe and more effective at improving aortic valve area and transvalvular gradient than the conventional single balloon technique.     

Rhabdoid Tumor of the Kidney Is a Component of the Rhabdoid Predisposition Syndrome

The rhabdoid predisposition syndrome (RPS) is characterized by pedigrees in which two or more individuals carry germline mutations of the hSNF5/INI1 tumor suppressor gene. The tumors associated with the syndrome include atypical teratoid/rhabdoid tumor (AT/RT), choroid plexus carcinoma, medulloblastoma, and extrarenal rhabdoid tumor. Rhabdoid tumor of the kidney (RTK) has not been described as part of the RPS. We report a case of a 7-month-old boy with RTK whose sister had a malignant cerebellar tumor followed by a malignant lung and pleural tumor of childhood with typical rhabdoid histology. Molecular genetic analysis of the RTK and tissue from the pleural tumor revealed in both cases identical nonsense mutations of the hSNF5/INI1 gene on chromosome 22q11.2, where thymidine was substituted for cytosine in base 472. The proband had an identical germline mutation. This is the fifth genetically analyzed RPS pedigree and the first to include an RTK.