Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance

Impaired glucose tolerance (IGT) is associated with defects in both insulin secretion and action and carries a high risk for conversion to non-insulin-dependent diabetes mellitus (NIDDM). Troglitazone, an insulin sensitizing agent, reduces glucose concentrations in subjects with NIDDM and IGT but is not known to affect insulin secretion. We sought to determine the role of beta cell function in mediating improved glucose tolerance. Obese subjects with IGT received 12 wk of either 400 mg daily of troglitazone (n = 14) or placebo (n = 7) in a randomized, double-blind design. Study measures at baseline and after treatment were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin sensitivity index (SI) assessed by a frequently sampled intravenous glucose tolerance test, insulin secretion rates during a graded glucose infusion, and beta cell glucose-sensing ability during an oscillatory glucose infusion. Troglitazone reduced integrated glucose and insulin responses to oral glucose by 10% (P = 0.03) and 39% (P = 0.003), respectively. SI increased from 1.3+/-0.3 to 2.6+/-0.4 x 10(-)5min-1pM-1 (P = 0.005). Average insulin secretion rates adjusted for SI over the glucose interval 5-11 mmol/liter were increased by 52% (P = 0.02), and the ability of the beta cell to entrain to an exogenous oscillatory glucose infusion, as evaluated by analysis of spectral power, was improved by 49% (P = 0.04). No significant changes in these parameters were demonstrated in the placebo group. In addition to increasing insulin sensitivity, we demonstrate that troglitazone improves the reduced beta cell response to glucose characteristic of subjects with IGT. This appears to be an important factor in the observed improvement in glucose tolerance.     

46-year-old patient with hemorrhagic diathesis and renal artery aneurysms. Type IV Ehlers-Danlos syndrome

To establish the medium-term results of our transplant population, we retrospectively reviewed the charts of 51 consecutive patients who underwent orthotopic heart transplantation between July 1988 and April 1995. These patients comprised two groups: group A consists of 26 patients (age 6 days to 16.4 years, median 1.4 years) with no previous heart surgery, and group B consists of 25 patients (ages 0.1 to 14.3 years, median 8.3 years), all of whom had heart surgery before undergoing transplantation. There was no difference between these groups in early or late survival rates, and neither age at transplantation nor sex was an indicator of survival. There have been 14 deaths, six early (before hospital discharge) and eight late. Early deaths have predominantly been attributed to long-term ventilation and hemodynamic instability before transplantation, and late deaths to graft coronary artery disease (n = 4), acute coronary vasculitis (n = 3), and acute cellular rejection (n = 1). Although infection has resulted in significant morbidity (57 hospital admissions), there have been no late deaths resulting from infection. Sepsis accounts for four early deaths in chronically ill patients. Orthotopic heart transplantation in the pediatric patient with and without previous heart surgery is a viable option for those with end-stage heart disease and those in whom other surgical options carry a prohibitively high mortality rate.     

Hernia survey of the Section on Surgery of the American Academy of Pediatrics

The members of the Section on Surgery of the American Academy of Pediatrics were surveyed to determine the practice of North American pediatric surgeons in infants with inguinal hernia (IH). Case-scenario multiple-choice-design questionnaires regarding hernias and hydroceles were sent to all members of the Surgical Section, and responses were received from 292 (50%). In healthy full-term infant boys with asymptomatic reducible IH, 82% of responders perform repair electively, no matter what the age or weight. In full-term girls with a reducible ovary, 59% perform surgery at the next available time; if the ovary is nonreducible but asymptomatic, 44% operate emergently or urgently and 42% at the next elective slot. In former preemies, the pattern of repair is as follows. (1) For those recently discharged after 2 months in the neonatal intensive care unit (NICU) with reducible IH, 65% perform the repair when convenient. (2) A general anesthetic is used in 70%; 15% use spinal anesthesia, and 11% use caudal block with sedation. (3) If the repair is done in the hospital outpatient (same-day) unit, 36% wait until 50 weeks postconception (PC) and 33% wait until 60 weeks PC. (4) if the baby's weight is at least 1,000 g. 71% perform the repair before discharge. The pain control choice after childhood IH repair is Tylenol for 30%, local infiltration biquivacaine for 30%, caudal block for 22%, regional block for 11%, and Tylenol/codeine combined for 7%. In 6-week-old full-term infants with communicating hydroceles without definite "hernia," two thirds treat as an IH with elective repair as soon as possible. With respect to contralateral exploration in infants with unilateral IH, 65% perform it in males if they are < or = 2 years of age and 84% use it in females of up to 4 years of age. This approach is not influenced by presenting side, presence of hydrocele, or history of prematurity. Laparoscopic evaluation of the contralateral IH is performed by only 6% of responders, 40% of whom use the open ipsilateral sac for laparoscope introduction.     

Babesial antibody dynamics after cattle immunisation with live vaccines, measured with an indirect immunofluorescence test

The efficacy of vaccination of Argentinean cattle against babesiosis and anaplasmosis using live immunogens was tested to detect specific antibodies in samples obtained about 60 days after vaccination. Under these conditions a higher than expected proportion of cattle failed to show antibodies against Babesia bigemina. Therefore, a study was designed to evaluate if this failure was due to insensitivity of the routine test to detect antibodies to B. bigemina or to lack of infectivity of the live vaccine. Four groups (G) of cattle were each inoculated subcutaneously with 10 million Babesia bovis (vaccinal strain R1A), 10 million B. bigemina (vaccinal strain S1A) and 10 million Anaplasma centrale (strain M1). G1 and G2 consisted of ten Angus bulls 20-24 months old and ten Angus bulls 15-18 months old, respectively; G3 and G4 consisted of ten and 16 Holstein 1-month-old male calves, respectively. Blood samples were obtained on days 0, 10, 20, 30, 40, 50 and 60 after vaccination and the sera were analysed with an indirect immunofluorescent (IFA) test to detect antibodies to B. bovis (baseline dilution for a positive result 1:60) and B. bigemina (baseline dilution 1:120). Positive IFA titres were considered as evidence of the infectivity of the Babesia vaccinal strains contained in the vaccine. All Angus bulls were found positive to antibodies against both Babesia species, by day 20 (B. bovis) and day 30 (B. bigemina), whereas 10-25% of Holstein calves were negative throughout. The partial lack of vaccine infectivity in the calves was considered to be a consequence of innate resistance of young calves to Babesia. Antibody titres to B. bovis and B. bigemina declined by day 60 after vaccination. However, all cattle that were positive to B. bovis antibodies on day 50 were still positive to the IFA test 10 days later while 10%, 30% and 12% of cattle of G1, G2 and G3 that were positive to B. bigemina antibodies on day 50 after vaccination were found negative to the IFA test on day 60. In future, samples taken on days 40-50 will be used for detection of B. bigemina antibodies in vaccinated cattle, on day 60 for A. centrale and on either occasion for B. bovis. The reaction to the inoculation of B. bigemina S1A strain appears to lag behind the reaction to B. bovis R1A strain. It is not certain if this is a normal reaction to this B. bigemina strain or the result of interaction with the B. bovis strain.