Adverse event associated with methionine loading test: a case report.

The death of a control subject after an oral load of methionine for a study of the possible relationship between homocysteine and Alzheimer's disease is reported. The subject developed postload plasma concentrations of methionine far beyond those reported previously in humans given the usual oral loading dose of methionine (100 mg/kg body wt). Her preload plasma metabolite values rule out known genetic diseases that might predispose one to unusually high methionine concentrations. The most likely explanation for these events is that the subject received a substantial overdose of methionine. The possibility that extremely high methionine concentrations may lead to severe cerebral effects is discussed, and it is recommended that any move to increase the sensitivity of the usual methionine loading test by increasing the dose of methionine either not be undertaken or be taken only with extreme care.

Linking theory of mind and central coherence bias in autism and in the general population.

Three experiments investigated whether 2 characteristic aspects of the psychological profile of autism, theory-of-mind deficits and weak central coherence, might be functionally related. Experiment 1 showed that in the general population, performance on a proposed test of theory of mind was inversely related to speed on the Embedded Figures Test, a measure of central coherence bias. Experiments 2 and 3 confirmed that poor theory-of-mind performance was linked to weak central coherence among typically developing children and among children with autism; however, the correlations between these measures were reliable only after accounting for differences in individuals' verbal mental ages. This pattern of results is interpreted in terms of a relationship between individual differences in theory of mind and central coherence bias, a relationship that is separate from any developmental differences in these domains.

Usefulness of thallium-201 for distinction of ischemic from idiopathic dilated cardiomyopathy.

Thallium-201 scintigraphic defects are observed in most patients with ischemic cardiomyopathy and also can be found in idiopathic dilated cardiomyopathy. To determine the ability of qualitative and quantitative perfusion parameters to differentiate these entities, thallium-201 exercise testing was performed in 51 patients with coronary arteriography referred for evaluation of severe congestive heart failure. All patients had a left ventricular ejection fraction < 35%. Thirty-one ischemic patients had coronary stenosis > 70% in > or = 1 artery, and 20 idiopathic patients had no coronary stenosis or identifiable cause of heart disease. Similar exercise capacity, ejection fraction and sex distribution were found in both groups. Ischemic patients more often had severe perfusion defects (97 vs 25%; p = 0.00001), large perfusion defects involving > or = 40% of the left ventricular contour (100 vs 80%; p = 0.01), and increased thallium-201 lung uptake (94 vs 65%, p = 0.01). Large severe defects were present in 90% of ischemic and only 5% of idiopathic patients. On quantitative analysis, the area of the thallium-201 curve less than normal was greater in ischemic than idiopathic patients (14.8 +/- 9.5% vs 3.3 +/- 2.8%; p = 0.001). The degree and severity of redistribution were similar in both groups. Multivariate analysis identified the qualitative parameters of increased thallium-201 lung uptake, severe defects and large severe defects as the only independent predictors of the presence of ischemic disease. The presence of large severe defects had a 97% predictive value for ischemic cardiomyopathy. The absence of severe defects had a 94% predictive value for idiopathic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular compatibility and renal graft survival--the HLA DQB1 genotyping.

Renal donor-recipient HLA DQB1 typing at the DNA level provides a new avenue to study graft survival (GS) and compatibility. HLA DQB1 genotypes of 63 renal donor-recipient pairs were typed simultaneously by assessing patterns from electrophoresed restriction fragments (PCR-RFLP) of amplified DNA (ADNA) and hybridization patterns of sequence specific oligonucleotides (PCR-SSO) of ADNA. Thus the clinical applicability of these two protocols for HLA DQB1 typing was assessed in addition to the compatibility study. Typing results of these two protocols gave overall agreeable results. Sixty-seven per cent of 150 alleles from 75 heterozygotes typed by both protocols had identical allelic type assignments. Serotyping shared more concordant results to PCR-RFLP determined types than to PCR-SSO determined types. The PCR-RFLP protocol can be easily implemented for clinical DNA typing because of its clarity in assigning allelic types and the possible handling of a small number of typing samples, even a single sample, in a single run. The degree of compatibility of these donor-recipient pairs was measured by matching (M) or mismatching (MM) the PCR-RFLP determined DQB1 allelic types. The Kaplan-Meier method was used to estimate GS. Significantly higher GS rates (P < 0.03) were found in donor-recipient pairs with 2 M (GS:74%) as compared with those with 1 M (GS:68%) or 0 M (GS:40%). Higher graft survival was also associated with 0 MM (GS:86%) compared with those with 1 MM (GS:60%) or 2 MM (GS:40%), although the significance level is P = 0.08 for both Mantel-Cox and Breslow tests. These findings indicate the importance of determining HLA DQB1 molecular alleles for assessing GS.

Molecular compatibility and renal graft survival--the HLA DRB1 genotyping.

HLA DRB1 allelic types were determined by using sequence-specific oligonucleotides for the analysis of 91 renal donor-recipient pairs that were followed for 30 months. The Kaplan-Meier method was used to evaluate graft survivals (GS) of the matched and mismatched groups. The degree of compatibility was measured by allelic type matches and mismatches of the pairs. Furthermore, HLA DR genotypes were categorized into five groups, namely DR1, DR2, DR4, the group that also has the DRw52 allele, and the group of DR7, DR9, and DR10. All types within a group were considered a match. Serotypes of the same study group were also included for comparison. Associations of superior GS with compatible DRB1 allelic types, serotypes, and grouped DRB1 types were observed. A significantly higher GS rate was found in donor-recipient pairs when HLA DRB1 types were analyzed by group mismatching (P = 0.03) rather than type mismatching (P > 0.34). Because of the numerous allelic types that can be assigned on the basis of nucleotide sequence variations, a larger number of donor-recipient pairs is required to derive statistically significant results.

Rewarming, ultraprofound hypothermia and cardiopulmonary bypass.

Rewarming, a key event in resuscitation from accidental, experimental and clinical hypothermia, is sometimes followed by neurologic, cardiac, and respiratory sequelae and may lead to death. The rate of rewarming has been implicated but not quantified as etiologic in these sequelae. Under anesthesia fifteen dogs were cannulated and connected to an extracorporeal circuit for oxygenation, core cooling and rewarming. They were subjected to ultra-profound hypothermia with a core (esophageal) temperature as low as 1.3 degrees C, cardiac arrest, blood substitution, and continuous low flow perfusion. After 2-3 hours of cardiac arrest, rewarming began. Mechanical activity of the heart was seen between 10 degrees and 28 degrees C and respiration resumed at 29 degrees C. The rewarming rates of the 15 dogs were retrospectively studied. They were placed into three categories (G) based on the outcome. G-I (N=2):no neurological complications, G-II (N=8):transient neurological problems, and G-III (N=5):death, mainly from cardiovascular and respiratory complications confirmed at death by autopsy. Heat gain by each animal was recorded as a function of time for all experiments. The time it took each dog to reach 35 degrees C was determined and a mean was calculated (rewarming rate). Normal body temperature for a dog is 37.8 degrees C. Statistical analysis (ANOVA) was performed ex post facto to determine the relationship between rewarming rate and outcome. Our data contradicts the notion that slow core rewarming from nadir to normal temperature offers better outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Repeated dose administration of desmopressin acetate in uncomplicated cardiac surgery: a prospective, blinded, randomized study.

The effects of single or repeated doses of desmopressin on blood loss were examined in uncomplicated cardiac surgery, while assessing the potential for thrombogenic side effects. Seventy patients undergoing elective coronary artery bypass grafting (CABG) were studied. Patients were randomized into three blinded groups: Group I received DDAVP (0.3 micrograms/kg), IV, after cardiopulmonary bypass (CPB) and 12 hours later in the Intensive Care Unit (ICU); Group II, DDAVP (0.3 micrograms/kg), IV, after termination of CPB and saline (placebo) 12 hours later in the ICU; Group III, saline (placebo) IV after CPB and 12 hours later in the ICU. Blood loss and bleeding time decreased for Group I at 24 hours (P < 0.04) when compared to Group III; however, blood product replacement, as well as intraoperative and total blood loss at 36 hours, were not different among treatment and control groups. There were four myocardial infarctions recorded in Group I, two in Group II, and one in Group III. These differences were not found to be statistically significant. It is concluded that in routine CABG the prophylactic use of single or repeat dose DDAVP does not effectively decrease blood loss or blood product replacement.

Pancreatic flush injury in combined pancreas-liver recovery.

The function of pancreatic grafts harvested from six pancreas-liver (PL) donors was compared to that of nine pancreas-alone (PA) donors. All donors had comparable physiological parameters. Pancreas and liver were flushed in situ with 4C Collins solution and the portal vein was vented immediately. The pancreaticoduodenal grafts were reflushed and stored in Collins solution (three PA and two PL), silica gel-filtered plasma (six PA and two PL), or University of Wisconsin solution (two PL). Later they were revascularized by the iliac vessels and drained into the bladder. All pancreas recipients were insulin-dependent. Serum glucose, amylase, lipase, blood urea nitrogen (BUN), creatinine, protein, albumin, and urine amylase, bicarbonate and pH were monitored for 12 days. Data were analyzed using the Mann-Whitney U-test and Fischer's exact test. The PL grafts received a significantly higher aortic flush volume (5983 cc vs 1622 cc, P = 0.001) than those in the other group. Recipients of PL grafts had higher serum amylase (335 vs 250 IU/l) and lipase (1048 vs 424 IU/l), significantly lower levels of urine bicarbonate (11.2 vs 27.1 mEq/l, P = 0.01), pH (6.8 vs 7.3, P = 0.04), and amylase (9202 vs 19,981 IU/l, P = 0.05) than those in the PA group.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma oxalate levels rise in hemodialysis patients despite increased oxalate removal.

The cause of secondary hyperoxalemia and oxalosis in patients on maintenance dialysis is unknown. The oxalate removal rate was determined in 26 patients on maintenance hemodialysis and 6 on continuous ambulatory peritoneal dialysis by measuring oxalate removed by dialysis and urinary excretion. The role of vitamin B6 deficiency and ascorbate in the raised plasma oxalate concentrations of these patients was evaluated. Plasma oxalate in hemodialysis patients, 442 +/- 41 micrograms/100 mL (mean +/- SE), and peritoneal patients, 394 +/- 115 micrograms/100 mL, were significantly higher than that in normal subjects, 11 +/- 1 microgram/100 mL (P less than 0.001). Average daily oxalate removal in subjects on hemodialysis, based on dialysis losses and urinary excretion, 35 +/- 3 mg/24 h, was significantly greater than urinary excretion of normal subjects, 26 +/- 1 (P less than 0.01). Oxalate removal from peritoneal dialysis patients, 28 +/- 2 mg/24 h, was not significantly different from that of hemodialysis patients or urinary excretion of normal subjects. Plasma ascorbate and B6 status were not correlated with plasma oxalate. A positive correlation between B6 deficiency and oxalate removal rate was not found. Plasma oxalate was correlated with time on dialysis (all patients) (P = 0.02). In a separate study of 15 hemodialysis patients followed over 2.3 +/- 0.2 yr, both plasma oxalate and oxalate removal rate significantly increased, P less than 0.001 and 0.05, respectively. It was concluded that oxalate removal rate is increased in hemodialysis patients and that the increased total body oxalate burden in these patients is not due to decreased removal. Although the increase may result from increased oxalate synthesis or gastrointestinal absorption, B6 deficiency and increased plasma ascorbate do not play a role.

Flow cytometric S fraction as a predictor of clinical outcome in cystosarcoma phyllodes.

Clinicopathologic characteristics were evaluated in 20 cases of cystosarcoma phyllodes in relation to clinical outcome. Flow cytometric DNA studies were carried out in 15 of these 20 cases. Stromal overgrowth and an infiltrating tumor border emerged as prominent histopathologic features that were associated with an unfavorable clinical outcome. Flow cytometric S fractions greater than 0.05 were associated with poor clinical outcome. There was no correlation between tumor ploidy and clinical outcome. There were no direct correlations between clinicopathologic features and flow cytometric measurements. Our data suggest that flow cytometric S fractions may be a useful predictor of clinical outcome in cystosarcoma phyllodes that can complement the traditional histologic analysis of these rare breast tumors.

Physiologic studies of urinary drained pancreaticoduodenal grafts in humans.

Exocrine function of urinary drained pancreas transplants (UDP) as determined by measurements of urinary pancreatic metabolites was assessed in 15 recipients. Normal UDP showed significantly higher levels (P less than 0.05) of urinary amylase, (42,931 +/- 5135 U/liter), HCO3 (27.12 +/- 3.18 meq/liter), and pH 7.83 +/- 0.15) than nine other recipients of enteric drained pancreas transplants with corresponding values of 168.00 +/- 2.00 U/liter, 3.20 +/- 0.20 meq/liter, and 6.08 +/- 0.27. These urinary metabolites dropped significantly (P less than 0.02) during rejection to 13,576 +/- 3446 U/liter, 19.22 +/- 5.74 meq/liter, and 7.06 +/- 0.14, respectively. These changes preceded elevation of blood sugar levels by 2-3 days. During rejection episodes, pancreatic grafts failed also to excrete bicarbonate and amylase significantly in response to secretion stimulation (P less than 0.05) contrary to nonrejecting pancreata. It is concluded that decreases in urinary amylase, HCO3, and pH observed with and without secretin stimulation are simple markers of pancreatic rejection.

The power of the Z statistic: implications for trauma research and quality assurance review.

The Z statistic can be used to test whether the observed number of survivors in a specific trauma population is significantly different from what would be expected based on the Major Trauma Outcome Study (MTOS) norms. However, as with any statistic, inferences based on the Z statistic should be made with care. This is particularly true when a non-significant Z statistic is observed. The purpose of this paper, using data from a large, urban trauma registry, is to illustrate how the power of the Z statistic, or its ability to detect a difference between observed and expected survival, is influenced by the magnitude of the difference, the direction of the difference, the survival probability distribution of the study population, and the sample size. The implications for trauma research and quality assurance review are discussed.

The utility of physiological status, injury site, and injury mechanism in identifying patients with major trauma.

It has been suggested that if triage criteria are to identify accurately patients with major trauma, not only physiologic status, but also anatomic site and injury mechanism must be assessed. This study examined the influence of physiologic, injury site, and injury mechanism criteria on the diagnosis of major trauma in 2,057 trauma patients. Because the Trauma Score was found to be a highly specific indicator of major trauma (98.7%), the strategy adopted for isolating the factors that minimize inappropriate triage was to determine which, alone or in combination, are the most effective in identifying patients with major trauma among those with high Trauma Scores (greater than 12). Based on this analysis, a set of triage guidelines was developed. The application of these guidelines to the study population indicated an undertriage rate of 4.1 to 6.3% and an overtriage rate of 16.8 to 21.3%, depending on the definition of major trauma.

Stressful work conditions and diastolic blood pressure among blue collar factory workers.

The authors examined the relationships between stressful work conditions and diastolic blood pressure among blue collar men employed in similar occupational settings. The study population consisted of 288 male, hourly workers, aged 40-63 years, employed for a minimum of 10 years at one of two plants in the metropolitan Pittsburgh, Pennsylvania area in January 1980. Blood pressure was assessed by the random zero muddler method by trained nurses at screenings between March 1981 and August 1982; 47 men who received pharmacologic treatment for previously diagnosed hypertension were excluded from the analyses. Multiple regression analyses showed that ratings of six (of 15) stressful work conditions as well as overall job dissatisfaction were significant predictors of diastolic blood pressure, controlling for age, body mass index, alcohol consumption, cigarette smoking habits, family history of hypertension, and severe noise-induced hearing loss. Men with elevated diastolic blood pressure reported having little opportunity for promotion and for participating in decisions at work, an uncertain job future, unsupportive coworkers and foreman, difficulties communicating with others, and overall dissatisfaction with the job. Additional stepwise multiple regression analyses showed that overall job satisfaction was related to low diastolic pressure among men from the plant rated as having overall good work conditions. These results are noteworthy because they support the importance of stressful work conditions and psychological reactions to those conditions in understanding the epidemiology of hypertension.

Anger-coping types, blood pressure, and all-cause mortality: a follow-up in Tecumseh, Michigan (1971-1983).

This study examined prospectively (1971-1983) the relationship between anger-coping types, blood pressure, and all-cause mortality in a sample of men and women aged 30-69 (n = 696) of the Tecumseh Community Health Study. Subjects who indicated that they were likely to suppress their anger in response to two hypothetical anger-provoking situations had 1.7 times the mortality risk of those who expressed their anger (95% confidence interval (CI) = 1.03-3.05). Subjects who suppressed their anger when unjustifiably confronted by their spouse had twice the mortality risk of those who expressed their anger (95% CI = 1.13-3.38). For high vs. low suppressed anger towards a policeman, the mortality risk was 1.24 (95% CI = 0.72-2.14). These relationships were invariant across age, sex, and education groups, even when medical risk factors were adjusted for, i.e., smoking, relative weight, blood pressure, coronary heart disease status, forced expiratory volume at one second (FEV1), and chronic bronchitis. However, suppressed anger measures significantly interacted with elevated blood pressure to predict the highest mortality risk. These results suggest that persons with high mortality risk can be identified in part by how they cope with anger, and by the joint effect of anger-coping type (a behavioral trait) and elevated blood pressure (a biologic trait).