Potential pitfalls in intraoperative parathyroid hormone measurements during parathyroid surgery.

BACKGROUND: The outcome of parathyroid surgery is often not clear for at least 24 h after the operation. A frozen section does not always distinguish between an adenoma and hyperplasia. Minimally invasive surgical techniques are being refined, so the need for perioperative assurance about the completeness of surgery has increased. The value of intraoperative parathyroid hormone (PTH) measurements in 26 surgical cases undergoing parathyroidectomy has been evaluated. METHODS: Twenty-one patients were diagnosed as having primary hyperparathyroidism, including two patients with multiple endocrine neoplasia type I (MEN I). Five patients had tertiary hyperparathyroidism, including one patient with X-linked hypophosphataemia and four with renal hyperparathyroidism (RHPT). Blood samples were taken at the onset of surgery, at the time of tumour resection and at 5-min intervals following removal of the tumour. PTH was measured using a PTH Turbo assay on the DPC Immulite analyser. RESULTS: Current practice suggests that the PTH concentration should fall to less than 50% of the pre-incision value or to less than 50% of the level at the time of tumour resection (time equals zero). PTH levels were therefore monitored at 5-min intervals following removal of the tumour. In most of the case studies PTH followed the suggested pattern, but not when further exploration was warranted to determine if another adenoma was present. In some cases the PTH levels fell by the appropriate margin to deem the procedure a success but at 10 min post-gland excision the PTH began to rise again. Further exploration was required to confirm the continued source of PTH. CONCLUSION: We recommend that intraoperative PTH measurements continue until at least 15 min post-gland removal in cases of suspected single-gland disease. A decline in PTH concentration to at least 50% of the pre-incision or time of gland resection levels should be observed. If the PTH remains elevated or rises again after an appropriate decrease in levels, then multigland disease or ectopic sources should be considered. Caution is recommended in interpreting intraoperative PTH measurements to ensure complete success of the surgical procedure.

External quality assessment of urinary steroid profile analysis.

BACKGROUND: Clinical samples were distributed on 10 occasions to six UK laboratories that perform urinary steroid profile analysis. Urine samples were from normal adult men and women, normal children and neonates. Samples from patients with Cushing's syndrome, virilization, adrenarche, obesity and congenital adrenal hyperplasia (21 and 17-hydroxylase defects) were also used for evaluation. METHODS: Samples were analysed by capillary column gas chromatography (all laboratories) after hydrolysis of conjugates and derivative formation (five laboratories) or by variation of 17-oxogenic steroid methodology (one laboratory). RESULTS: For each distribution of samples, the performance of the participants was compared for quantitative analysis, and user comments were summarized. Quantitative results showed variation without necessarily biasing the result. Comments varied considerably in length. The interpretations did not always lead to a clear diagnosis or advise about appropriate further tests. CONCLUSIONS: This pilot urine steroid profiling scheme has clearly identified the requirement for external quality assessment. It is now hoped to offer this scheme worldwide in collaboration with the European Research Network for the Evaluation and Improvement of Screening, Diagnosis and Treatment of Inherited Disorders of Metabolism (ERNDIM).

Faecal elastase 1: a marker of exocrine pancreatic insufficiency in cystic fibrosis.

Pancreatic elastase 1 (E1), a digestive protease, is synthesized by the acinar cells of the pancreas. Using an enzyme-linked immunosorbent assay, we evaluated stool E1 levels in the following groups of patients. (a) Specimens submitted for occult blood examination from 20 adults, over 3 consecutive days, to assess the inter-day variability in E1 excretion. There were no symptoms suggestive of pancreatic insufficiency in this group. The mean E1 concentration over all samples was 457 micrograms E1/g stool (range 124-1683). The intra-assay variation was 6.4% (n = 14) and the inter-assay variation was 8.8% (n = 12). The mean intra-patient variation was 17%. (b) Cystic fibrosis (CF) patients. Eight patients had E1 levels in the reference range (> 200 micrograms E1/g stool). The remaining 25 patients had undetectable E1 levels. (c) A control group of children presenting with unexplained bronchiectasis and/or recurrent respiratory infections and no symptoms of pancreatic dysfunction. The mean E1 concentration in the group was 519 micrograms E1/g stool (range 139-1941). There was no significant difference in E1 concentrations between the two non-CF groups, nor between the pancreatic-sufficient CF patients when compared with both non-CF groups. There was a significant difference between the pancreatic-sufficient and -insufficient CF groups (P < 0.001) using the Mann Whitney U test. All fifteen CF patients who were delta F508 homozygotes had undetectable E1. It may be possible to relate CF genotype to the presence or absence of E1 and to the degree of pancreatic insufficiency. Measurement of faecal E1 in children with CF appears to differentiate them into a group of children with normal pancreatic function and a larger group with severe insufficiency.

Ontogeny of dry gas hyperpnea-induced bronchoconstriction in guinea pigs.

Adolescent guinea pigs (AGPs) demonstrate dry gas hyperpnea-induced bronchoconstriction (HIB) that shares key features with HIB in humans with asthma. The airways of immature animals exhibit enhanced reactivity to diverse types of stimulation. We tested whether dry gas HIB is also increased in newborn guinea pigs (NGPs). We quantified HIB as the fractional increase of respiratory system resistance (Rrs) over baseline (BL) in five 4- to 7-day-old NGPs after 10 min of hyperpnea, as well as changes in Rrs elicited by intravenous methacholine or capsaicin, and compared these responses with those of AGPs. During hyperpnea, analogous stimuli were delivered by mechanically imposing hyperpnea at 3.0, 4.5, and 6.0 times quiet eucapnic minute ventilation (VE). In AGPs, hyperpnea caused significant bronchoconstriction that increased with VE; peak fractional increase of Rrs was 7.6 +/- 2.0 times BL. In contrast, hyperpnea caused insignificant bronchoconstriction in NGPs (1.4 +/- 0.2 times BL after the largest VE; P < 0.05 vs. AGP). Responses elicited by methacholine (10(-10)-10(-7) mol/kg) or capsaicin (0.01-10.0 microgram/kg) were similar in NGPs and AGPs. In AGPs, hyperpnea suppressed HIB until posthyperpnea. To determine whether the reduced HIB of NGPs was caused by enhanced suppression, NGPs and AGPs were administered acetylcholine (10(-10)-10(-7) mol/kg i.v.) during BL eucapnic ventilation and during eucapnic hyperpnea with warm humidified gas. Responses to acetylcholine were suppressed in AGPs and NGPs to a similar degree. We conclude that HIB is markedly diminished shortly after birth in guinea pigs and that it increases substantially during maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Ontogenic expression of acetylcholinesterase activity in trachealis of young swine.

Previous investigations have demonstrated that cholinergic contraction of porcine tracheal smooth muscle (TSM) decreases between the second and tenth weeks of life. In this investigation, we hypothesized that the greater contractile response to acetylcholine (ACh) in TSM of 2-wk-old swine (2ws) vs. 10-wk-old swine (10ws) was the result of a relative decrease in activity of acetylcholinesterase (AChase). To examine this hypothesis, we assessed AChase activity directly in homogenates of TSM from eight 2ws and seven 10ws using a newly adapted method that measures the rate of cleavage of acetylthiocholine; enzyme activity was expressed as absorbance units per minute per milligram protein. The AChase from tissues of both age groups saturated at approximately 3 mM substrate. However, maximal AChase activity (Vmax) was significantly greater in 10ws than 2ws. Eadie-Hofstee analysis of enzyme kinetics revealed similar Michaelis-Menten constants for 2ws and 10ws. The concentration of physostigmine (PS), an inhibitor of cholinesterase, that elicited half-maximal inhibition of AChase activity also was similar for 2ws and 10ws. In separate studies, contraction of TSM strips was assessed in vitro at optimal resting length and expressed as a function of maximal force generation to potassium chloride. Strips of TSM from 2ws contracted with greater force than those of 10ws. After pretreatment with 10(-8) M PS, contractile forces were similar in 2ws and 10ws. We conclude that AChase activity measured directly in muscle homogenates is significantly reduced in TSM of 2ws vs. 10ws and that this may result in augmented contraction to ACh under conditions of zero-order kinetics.

Effect of maturation on topographic distribution of bronchoconstrictor responses in large diameter airways of young swine.

We studied the effect of maturation on the topographic distribution of airway constriction in Generations 0 (trachea) through 6 in fourteen 2-wk-old swine (2ws) and sixteen 10-wk-old swine (10ws) in vivo and in excised airways from seven 2ws and seven 10ws in vitro. Animals were anesthetized with chloralose-urethane and received beta-adrenergic blockade and vagotomy prior to generation of random-order, dose-response curves with i.v. methacholine (MCh) and histamine (His) or serotonin (5HT) given intravenously. Lung resistance (RL) was measured, and airway diameter was assessed by tantalum bronchograms obtained at functional residual capacity for each dose of agonist. Baseline RL was substantially greater in 2ws (48 to 62 cm H2O/L/s) than in 10ws (9 to 11 cm H2O/L/s; p less than 0.001 for all groups). Intravenous infusion of 10(-6) mol/kg MCh caused a 416 +/- 110% increase in RL in 2 ws and a 314 +/- 32% increase in RL in 10 ws (p = NS); airway diameter (Daw) decreased by 10 +/- 1% (Generation 2) to 27 +/- 4% (Generation 6) in 2ws and from 8 +/- 2 (Generation 2) to 17 +/- 4% in 10ws. Intravenous infusion of 10(-6) mol/kg His caused a 513 +/- 85% increase in RL in 2ws and a 276 +/- 17% increase in RL in 10 ws (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)