A fast protein liquid chromatography (FPLC) method for study of thyrotropin-releasing hormone (TRH) and its metabolite histidyl-proline diketopiperazine (CHP) in human blood: degradation in liver and pancreatic diseases.

We have developed a convenient method combining fast protein liquid chromatography (FPLC) with sensitive radioimmunoassay (RIA) for thyrotropin-releasing hormone (TRH) to separate and identify TRH and its metabolite histidyl-proline diketopiperazine (CHP) and applied this to study inactivation of TRH by blood extracts from patients with liver cirrhosis (LC) and acute edematous pancreatitis (AP). Blood samples spiked with TRH and CHP were extracted by cold methanol and injected on a reverse-phase FPLC column. A linear gradient was applied for separation. Subsequent analyses of fractions by RIA for TRH revealed that only fractions 9-10 contained TRH. Separation by retention time (9.9 +/- 0.8 min for TRH, 10.5 +/- 0.6 min for CHP, mean +/- SEM) was highly reproducible. For degradation studies, pooled sera from patients with LC and AP were incubated with TRH and CHP for 60 min. Inactivation of TRH was less rapid in the presence of blood extract from LC patients than that from normal subjects or AP patients. CHP was more stable than TRH. These data suggest that activity of TRH-degrading enzymes is reduced in liver disease, whereas it does not appear to be altered in AP. Degradation of CHP does not closely reflect metabolic processing of its major precursor. This rapid and sensitive method may be applicable for further investigations on the metabolism of TRH in organic fluids.

Evaluation of thyrotropin secretion before and after TRH by third generation chemiluminescent assay. Assessment of subclinical hyperthyroidism.

The recent introduction of third generation assays for TSH has led to a considerable improvement of assay sensitivity. To assess the clinical significance of subnormal basal TSH (b-TSH) values (< 0.2 microU/ml), we investigated b-TSH and TRH-stimulated TSH (r-TSH) by means of a new, highly sensitive immunochemiluminometric assay in 105 euthyroid subjects, 45 patients with overt hyperthyroidism and 18 patients suspected of having subclinical hyperthyroidism. A weak, albeit statistically significant, correlation (r = 0.48) was found between b-TSH and r-TSH and also between b-TSH and delta-TSH (r = 0.31) in euthyroid subjects. Consideration of b-TSH alone correctly identified 90 % of euthyroid subjects in this group; 10 of 105 apparently euthyroid subjects presented delta-TSH suggesting subclinical hyperthyroidism. While b-TSH was detectable (> 0.04 microU/ml) in 8 of 45 (18%) of hyperthyroid patients, all (100%) were abnormal in both b-TSH and r-TSH. 14 of 18 (78%) of patients with subclinical hyperthyroidism exhibited a blunted TSH response to stimulation (delta-TSH < 2 microU/ml). These results suggest that although the new generation of TSH assays can be a valuable addition to the diagnostic arsenal of thyroid function tests, certain limitations must still be accepted. Specifically, b-TSH in the "grey zone" (0.1-0.2 microU/ml) appears to be a less than reliable predictor of thyroid function.

[Micturition disorders following spinal anesthesia of different durations of action (lidocaine 2% versus bupivacaine 0.5%)]. / Miktionsstörungen nach Spinalanästhesie unterschiedlicher Wirkungsdauer (Lidocain 2% versus Bupivacain 0.5%).

Disturbances of micturition following spinal anaesthesia are considered to be rare and harmless side effects of this technique. For this reason, we set up a prospective study to investigate their incidence, characteristics and intensity. Our special interest was directed at the influence of the duration of action of local anaesthetics. METHODS. In a randomized, double-blind study, two groups, each consisting of 73 trauma surgical and orthopaedic patients, received isobaric spinal anaesthesia with either lidocaine 2% or bupivacaine 0.5%. From the 1st to the 3rd postoperative day, the patients were interviewed daily and asked specifically about disturbances of micturition. RESULTS. The two groups were comparable in terms of clinical data, spinal anaesthesia and surgery. Disturbances of micturition occurred only during the first 24 h and were observed in a total of 42%. They were about twice as frequent after bupivacaine (56%) as following lidocaine (27%). After bupivacaine there was a higher rate of difficult micturition or complete inability to micturate in the presence of an urge to urinate, carbachol medication and catheterization of the urinary bladder. Sex and age had no influence on the incidence. A history of disturbances of micturition increased their frequency. DISCUSSION AND CONCLUSIONS. Disturbances of micturition are the most common side effect of spinal anaesthesia during the first 24 h after surgery. Their higher frequency following the longer acting bupivacaine may be evidence of longer lasting blockade of the efferent sacral parasympathetic fibers innervating the detrusor vesicae muscle, leading to inhibition of bladder voiding. The consequences of these disturbances, if not correctly managed, may be distension of the urinary bladder with ensuing infection and loss of tone of the detrusor muscle. Various measures are recommended: choice of the longer acting local anaesthetic only if necessary, careful control of bladder filling, restrictive infusion of fluids, early mobilization, carbachol, catheterization in good time, prophylactic placement of an indwelling catheter in patients with previous disturbances.