Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool

The use of livers from anti-hepatitis B core (HBc) positive donors can alleviate donor shortage. Nineteen of 367 (6%) adults receiving anti-HBc positive allografts [three were hepatitis B antigen (HBsAg) negative, hepatitis B antibody (HBsAb) positive; four were HBsAg positive and 12 were not exposed to hepatitis B viral (HBV) infection] were retrospectively reviewed. In HBsAg negative recipients, immunoprophylaxis (IP) was guided by viral serology and immunohistochemistry (IH) of day 0 and day 7 liver biopsies. If IH was negative, IP was stopped. None of three HBsAg negative, HBsAb positive recipients infected; one (replicating) of four HBsAg positive recipients reinfected and seven of eight (87.5%) HBsAg, HBsAb negative recipients, who did not receive long-term IP, infected after a median time of 2 years (range 1-5); one patient died of liver failure. Four HBsAg, HBsAb negative recipients, receiving life-long IP, remained infection free. Anti-HBc positive donor livers must be directed selectively first to HBsAg positive recipients, next to recipients having HBV antibodies and finally to HBV-naive recipients. Identification of both donor and recipient risk factors for HBV infection before transplantation allows indiscriminate use of antiviral prophylaxis. The necessity for IP therapy should be guided by HBV-DNA testing of donor liver tissue and serum. IH of early liver biopsies is an unreliable marker for predicting antiviral treatment requirements.     

A randomized, blinded trial of uncooked cornstarch to diminish nocturnal hypoglycemia at Diabetes Camp

Objective: To determine if uncooked cornstarch, as part of the evening snack, can avert nocturnal hypoglycemia in type 1 diabetes. Research Design and Methods: Fifty-one campers and counselors at the American Diabetes Association Camp in San Bernardino, CA were randomly assigned to receive 5 g of uncooked cornstarch as part of the 21:00 evening snack vs. a standard snack of equivalent carbohydrate content. Each snack was given for five nights and the participants and medical personnel were blinded as to assignment. Midnight and 07:00 finger stick blood glucose levels were compared with values <60 mg/dl defined as hypoglycemia and values >250 mg/dl defined as hyperglycemia. Results: There were 218 midnight and 222 07:00 values for comparison. There were six episodes of hypoglycemia at midnight and nine episodes of hypoglycemia at 07:00 for the cornstarch snack nights vs. 30 hypoglycemia episodes at midnight and 21 at 07:00 for the standard snack nights (P < 0.001 and < 0.05, respectively). There was no difference in the number of hyperglycemic events at midnight or 07:00 for the cornstarch vs. standard snack nights. At midnight, 12% of campers had hypoglycemia after the cornstarch snack vs. 46% after the standard snack (P < 0.001), and at 07:00, 16% had hypoglycemia after cornstarch vs. 26% after the standard snack (P = 0.327). Conclusions: These data suggest that uncooked cornstarch, as part of the evening snack, can diminish the nighttime and morning hypoglycemia associated with type 1 diabetes, without causing hyperglycemia.     

Effect of the aromatase inhibitor 4-hydroxyandrostene-3,17-dione progesterone synthesis by human luteal cells

The authors studied the effects of 4-hydroxyandrostene-3,17-dione (4-OHA) on progesterone (P), 17 beta-estradiol (E2), and 20 alpha-hydroxy-4-pregnen-3-one synthesis and pregnenolone accumulation in cultured human midluteal cells. A dose-dependent inhibition with and without human chorionic gonadotropin (hCG) of E2 and P production was observed. The accumulation of pregnenolone was significantly enhanced three to fourfold by 4-OHA in this culture system, as compared with control value. In addition, a sevenfold increase on pregnenolone accumulation was observed in the presence of 4-OHA plus 10 IU of hCG as compared with control values and 2.2-fold as compared with the 4-OHA treatments. These in vitro findings indicate a direct effect of 4-OHA on luteal steroidogenesis. Nevertheless, the suppressive effect of 4-OHA on P and E2 production is located at different sites of the steroidogenic pathway. In addition, the results demonstrate that hCG in the presence of 4-OHA stimulated pregnenolone accumulation, suggesting that the inhibition of P synthesis is in some steps after the formation of pregnenolone. These data indicate that the actions of 4-OHA on P or E2 formation have different inhibitory mechanisms.     

Iatrogenic renal disease

We studied iatrogenic problems in nephrology by classifying all patients for nephrology consultation into nine presenting syndromes and seven etiologic groups. One hundred (2.2%) of all admissions were seen in nephrology consultation. Acute renal failure was the most common presenting syndrome, accounting for 59% of the consultations. Forty-one of the 100 consultations (1% of all admissions) had a renewal syndrome of iatrogenic origin. Of these 41 patients, 38 had acute renal failure and three had fluid and electrolyte problems. Twenty of the 41 patients had drug-induced problems. Eighteen of these patients were dehydrated, and in three patients, acute renal failure occurred after surgery. Of the 20 patients with iatrogenic renal problems caused by drugs, seven problems were antibiotic related, five were due to diuretics, four were due to nonsteroidal anti-inflammatory drugs, three were due to angiotensin-converting enzyme inhibitors, and one was from the use of contrast medium. The 41 patients with iatrogenic-related renal disease were older than the other 59 patients (61.8 vs 49.3 years). Iatrogenic renal disease developed in 1% of all patients admitted to a tertiary care hospital, and 12% of these patients died. The most common renal syndrome is acute renal failure, most often caused by nephrotoxic drugs. The incidence can probably be decreased by better monitoring of body weight and fluid balance to prevent dehydration and by the avoidance of nephrotoxic drugs.     

Plasma C-peptide and cognitive performance in older men without diabetes.

BACKGROUND: Emerging evidence suggests that type 2 diabetes may be related to diminished cognition, but little data are available directly regarding the role of insulin levels. OBJECTIVE: The objective of this prospective cohort study was to examine the relation of insulin secretion to cognitive function among men without diabetes. SETTING: The study setting was the Physicians' Health Study-U.S. male physicians. PARTICIPANTS: Three hundred sixty-seven men who provided blood samples in 1982, when they had no lifetime history of diabetes and ranged in age from 47-65 years (mean age: 57 years). MEASUREMENTS: The authors assayed plasma C-peptide, reflecting insulin secretion, in the stored blood samples. Beginning in 2001, an average 18 years after blood collection, the authors administered telephone interviews, including tests of general cognition (Telephone Interview of Cognitive Status [TICS]), verbal memory, and category fluency. The authors used regression models to estimate mean differences in cognitive performance across levels of C-peptide controlling for a wide variety of potential confounding factors. RESULTS: On the TICS, men in the top tertile of C-peptide performed significantly worse than those in the bottom (multivariable-adjusted mean difference: -1.01 points, 95% confidence interval: -1.78 to -0.24); this apparent impact of C-peptide on cognition was equivalent to the cognitive differences the authors observed between men 6 years apart in age. Performance on the global score (combining results from all the individual tests) and verbal memory score (combining results from four tests of verbal memory) appeared lower among men in the highest C-peptide tertile, but results were not statistically significant. CONCLUSION: Higher midlife insulin secretion may be related to decreased later-life cognitive function, even among men without diabetes.