Autoantibodies to Human Tissue Transglutaminase: Superior Predictors of Coeliac Disease

Background: Using selected sample populations, we compared sensitivity and specificity of autoantibodies to guinea pig and human tissue transglutaminase to assess if the human antigen is superior for predicting coeliac disease. Methods: Four commercial enzyme-linked immunoassay kits using human tissue transglutaminase as antigen were used to measure autoantibody levels in serum samples from untreated adult coeliacs ( n = 32). They were from a series of 130 cases diagnosed between 1997 and 1999 and chosen to bias the group towards subjects with negative autoantibodies when measured with guinea pig tissue transglutaminase as antigen. Samples from 38 control subjects (biased towards false-positive levels with guinea pig antigen) were used to compare specificity. We also assessed if human antigen kits could differentiate between levels in normal subjects and in selective IgA deficiency. Results: Sensitivity for coeliac disease in this selected group using the human antigen kits ranged from 88% to 100%. Three kits showed significantly higher specificity (82%-97%, P < 0.05) than the guinea pig antigen kit (71%) for the samples studied. No kit achieved complete separation between normal autoantibody levels and lower levels in selective IgA deficiency. Conclusions: All human antigen kits showed significantly higher sensitivity for coeliac disease compared to guinea pig antigen ( P < 0.001). Receiver operating characteristic curves confirmed the superior diagnostic accuracy of the human antigen kits.     

Retrospective direct comparison of three intraarticular anterior cruciate ligament reconstructions.

A long-term retrospective study (minimum 5 years) was done looking at three groups of anterior cruciate deficient knee patients using both subjective and objective anterior cruciate tests. Twenty-seven chronic anterior cruciate ligament deficient knees reconstructed with the middle third of the patellar tendon and 28 chronic anterior cruciate ligament deficient knees reconstructed with the semitendinosus tendon were included in this consecutive group of patients and were felt to be directly comparable. It was found that the chronic anterior cruciate ligament deficient group reconstructed with the semitendinosus tendon had 4 excellent, 10 good, 7 poor, and 7 failures with an objective score averaging 4.5 of a possible 12, while the comparable group reconstructed with the middle third of the patellar tendon had 16 excellent, 7 good, 3 poor, and only 1 failure with a score of 10 of a possible 12 (P less than 0.0032). For completeness sake, 20 anterior cruciate deficient knees from this group of consecutive patients that were reconstructed acutely with the semitendinosus tendon were also examined. This group had 8 excellent results, 9 good, 3 poor, and no failures with a score of 9.8 (P less than 0.03 compared to the other group using the semitendinosus tendon). This comparison between the two groups where the semitendinosus tendon was used in the anterior cruciate ligament reconstruction was made only to show the difference between studies dealing with knee reconstructions. There may be a significant difference between a study dealing with acutely reconstructed knees versus one focusing on chronically reconstructed knees, most likely because of both patient selection and time between injury and reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variation in susceptibility to atherosclerosis among inbred strains of mice

The effect of short-term exercise withdrawal on plasma lipoproteins, apoprotein A-I (Apo A-I), and lecithin:cholesterol acyltransferase (LCAT) was studied in moderately trained lifestyle exercisers. Eight endurance-trained men, age 18-45 years (means = 29 years), withdrew from aerobic activity for 6 weeks, while an age and fitness-matched control group (n = 9) maintained normal exercise habits. A baseline period that included two blood samplings preceded the detraining intervention. Plasma total cholesterol (TCHOL), HDL cholesterol (HDL-C) and triglyceride (TG) levels were determined weekly. Other blood variables (HDL2-C, HDL3-C, Apo A-I, and LCAT), % fat, and aerobic capacity (VO2max) were measured pre-, mid-, and post-experiment. A two-way repeated measures analysis of variance (ANOVA) indicated that the 6-week exercise withdrawal period failed to elicit significant mean changes in any blood variable, % fat, or VO2max. Therefore, a short-term layoff from aerobic activity by moderately trained, chronic exercisers generally does not adversely affect the blood lipoprotein profile or aerobic capacity.     

The epidemiology of cytomegaloviral infection in women attending a sexually transmitted disease clinic

To test the hypothesis that cytomegalovirus (CMV) is sexually transmitted, we examined the association of CMV infection with indices of sexual activity in 347 women attending a sexually transmitted disease (STD) clinic. Stepwise multivariate logistic regression analysis showed that seropositivity to CMV (complement-fixation antibody titer, greater than or equal to 1:8) was most closely associated with number of sex partners in the subjects' lifetime (P less than .0001), young age at first sexual intercourse (P = .0002), and nonwhite race (P = .0007). Among seropositive women, cervical shedding of CMV was most strongly associated with younger age (P = .0001) and the presence of cervical chlamydial infection (P = .016). Among 84 seronegative women followed up for a mean of 18.4 weeks, 11 (13%) developed primary CMV infections, an annual incidence of 37%. Sexual contact seems to be an important mode of acquisition of CMV in some young women.     

Pituitary binding of vasopressin is altered by experimental manipulations of the hypothalamo-pituitary-adrenocortical axis in normal as well as homozygous (di/di) Brattleboro rats

In the present study we report the properties of vasopressin (VP) receptors in the anterior pituitary gland and show that the number of these receptors is markedly affected by adrenalectomy and hypothalamic lesions. VP-binding activity was assayed in particulate fractions of rat anterior pituitary glands using tritium-labeled arginine VP ([3H] AVP) as tracer. In the presence of Mg2+ the radioligand interacted with a single class of high affinity, low capacity binding sites. Magnesium ions modulated the affinity of the receptors but had no effect on binding capacity. Guanine nucleotides decreased the amount of tracer bound in a dose-dependent manner by increasing the dissociation constant (Kd) of the binding reaction by approximately 2-fold. Increasing the concentration of Mg2+ did not prevent this effect. Bilateral adrenalectomy (ADX) decreased pituitary AVP-binding activity: binding fell by 30% 4 h after surgery and declined further to 10% or less of control at 4 days. The decrease in binding was primarily due to a reduction in the number of receptors. Daily administration of corticosterone inhibited the reduction of binding activity at 4 days in a dose-dependent manner. Destruction of hypophyseotropic VP neurons by means of surgical lesioning of the hypothalamic paraventricular nucleus or the medial basal hypothalamus abolished the effect of ADX on pituitary AVP binding at 24 h but only attenuated the degree of receptor loss at 4 days. Furthermore, the lesions themselves caused a significant (approximately 30%) reduction in receptor number 4-7 days after hypothalamic surgery. Adrenalectomy reduced pituitary AVP-binding activity in homozygous (di/di) Brattleboro rats. The extent as well as the time course of the loss of receptor activity resembled that in normal rats. Rat anterior pituitary segments were exposed to synthetic CRF, AVP, or oxytocin (all 10(-7) M) for 4 h in vitro, and [3H] AVP-binding activity was subsequently determined. Both AVP and oxytocin reduced the amount of radioligand bound, while CRF had no effect. These observations allow the following conclusions: Magnesium ions and guanine nucleotides modulate the affinity of pituitary AVP receptors by different mechanisms and have no effect on binding capacity; Pituitary receptors for AVP are regulated by the amount of AVP released by paraventricular nucleus neurons as well as through a mechanism that requires the presence of corticosterone; Homozygous Brattleboro rats may respond to ADX by increased hypothalamic release of an endogenous ligand for pituitary AVP receptors.     

Role of technology in controlling health care costs

The objectives of medical technology are to define basic knowledge about the function of the body and to aid in making patients better. Because the escalation of costs for advanced technology has been dramatic, it has been labelled one of the culprits for the great increases in health care costs in the past decade. Yet technology can improve the quality of care while providing mechanisms for lowering costs. Such an approach requires improved productivity. Several approaches to improve productivity, with emphasis on the electronic and computer revolution that has been brought to medicine, are discussed. In addition, it is suggested that the use of technology gives medical staff more time to meet the personal needs of patients.     

Cardiac arrhythmias in patients with surgical repair of Ebstein's anomaly

Preoperative, perioperative and postoperative arrhythmias in 52 consecutive patients who underwent operation for Ebstein's anomaly were reviewed. There were 25 male and 27 female patients (mean age 18 years, range 11 months to 64 years). Thirty-four patients had one or more documented arrhythmias preoperatively (18 had paroxysmal supraventricular tachycardia, 10 had paroxysmal atrial fibrillation or flutter, 13 had ventricular arrhythmia and 3 had high grade atrioventricular block). Seven patients without documented arrhythmias had a history typical of tachyarrhythmias. During the perioperative and early postoperative periods, 14 patients had atrial tachyarrhythmias and 8 had ventricular tachycardia or ventricular fibrillation. There were seven deaths between day 1 and 27 months after operation. Five of these deaths were sudden (all in male patients, aged 12 to 34 years), and four of the patients had had perioperative ventricular tachycardia or ventricular fibrillation. One patient was taking one antiarrhythmic agent and another patient was taking two at the time of sudden death. Of the 18 patients with paroxysmal supraventricular tachycardia and 9 patients with paroxysmal atrial fibrillation or flutter preoperatively who were followed up for a mean of 40 and 36 months, respectively, 22 and 33% continued to have symptomatic tachycardia. Of the 11 patients (mean age 9 years) without preoperative documentation or symptoms of arrhythmia, follow-up data were obtained (range 1 to 144 months, mean 31) in 9 patients. None died suddenly or developed symptomatic arrhythmia.