Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness

OBJECTIVE Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration. PATIENTS AND DESIGN Critically ill adults (n=40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n=10), GHRH and GHRP-2 (n=10), GHRP-2 and GHRH+GHRP-2 (n=10), GHRH+GHRP-2 and GHRH+GHRP-2+TRH (n=10). The GHRH and GHRP-2 doses were 1μg/kg and the TRH dose was 200μg. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection. MEASUREMENTS Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA. RESULTS Critically ill patients presented a striking GH response to GHRP-2 (mean±SEM peak GH 51±9 μg/l in older patients and 102±2μg/l in younger patients; P=0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P=0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P=0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P=0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response < ninefold (P=0.005), elicited a 60% rise in serum T3 (P=0.01) and an 18% increase in T4 (P=0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P=0.007). GHRP-2 increased basal serum cortisol levels (531±29nmol/l) by 35% (P=0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P=0.05). CONCLUSIONS The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine.     

Presence of antibodies to ubiquitin during the autoimmune response associated with systemic lupus erythematosus.

Sera from patients with systemic lupus erythematosus (SLE) were shown to react with both ubiquitin and a synthetic fragment of it (residues 22-45) in an ELISA and with ubiquitin in immunoblotting experiments. Close to 80% of lupus patients possessed ubiquitin antibodies, whereas only 55% of them possessed native DNA antibodies, a marker of SLE. Less than 16% of patients with other rheumatic autoimmune diseases possessed antibodies to ubiquitin. Our results indicate that the combined measurement of antibodies to native DNA and to ubiquitin could appreciably increase the detection of SLE cases (up to 85% in our study). It is suggested that ubiquitin, a heat shock protein, could be involved in antibody formation against ubiquitin-protein conjugates present during cellular injury and that this represents a major characteristic of the autoimmune response in SLE.     

Peri-operative liver graft function: monitoring using the relationship between blood glucose and oxygen consumption during anaesthesia

The purpose of our study was to test the hypothesis that the quotient between plasma glucose and whole body oxygen consumption (VO2) as a 'metabolic index' is a sensitive indicator of early graft function. Arterial levels of glucose and oxygen consumption were determined in 100 consecutive patients during orthotopic liver transplantation performed without anhepatic veno-venous bypass. Patients were divided into survivors with no obvious problems related to graft function and those with primary nonfunction of the graft. The neohepatic increase in VO2 was significantly higher in survivors (112 +/- 4 vs 88 +/- 11 ml.min-1.m-2; p < 0.05), whereas blood glucose levels after reperfusion were higher (352 +/- 18 vs. 287 +/- 36 mg dl-1) in those with primary non-function of the graft. The calculated metabolic index was also higher (4.02 +/- 0.93 vs 2.67 +/- 0.45, p < 0.05) in patients with primary nonfunction of the graft. Our principal conclusion was that 92% of normal functioning liver grafts could be classified correctly by the metabolic index immediately after reperfusion, whereas glucose levels and VO2 alone classified only 67% and 70% of normal functioning liver grafts correctly.     

The andrology laboratory in an Assisted Reproductive Technologies program. Quality assurance and laboratory methodology.

Assuring the highest possible quality of care to the patient is the first goal of the andrology laboratory. Quality control and quality assurance as they apply to the andrology laboratory are outlined, and special problems in quality control for sperm function assays are addressed. An example of the patient review process is presented. Quality of care also depends on the ability of the laboratory to perform appropriate tests of sperm function that can diagnose sperm defects, predict success or failure of in vitro fertilization, and lead to rational therapies for sperm dysfunctions. Methods for, and diagnostic value of, sperm swim-out, enhanced sperm penetration assays, acrosome reaction assessment, motility analysis of capacitating sperm, and sperm-zona binding assays are reviewed. No single test, other than in vitro fertilization itself, is capable of providing a complete diagnosis or a highly accurate prediction. A battery of sperm function tests, arranged in an algorithm, is presented as a theoretically better approach.     

Noninvasive in vivo 13C-NMR spectroscopy in the rat to study the pharmacokinetics of 13C-labeled xenobiotics.

Noninvasive NMR methodology has been developed to enable monitoring of 13C-labeled xenobiotics in the rat in vivo. 2,2-Dichloro-1-(2-chlorophenyl)-1-(4-chlorophenyl)-[3-13C]-propane can be detected in the liver of intact rats by in vivo 13C surface coil NMR spectroscopy after ip administration of the compound. The experiments were performed at 1.9 and 9.4 Tesla. The intrahepatic changes of the signal intensity of the labeled compound were followed as a function of time. In the days following administration, the concentration decreased and dropped to values below the detection limit after 12 days. The study demonstrates the feasibility of studies on pharmacokinetics of 13C-labeled compounds in the rat using noninvasive, in vivo surface coil NMR spectroscopy in animals. The sensitivity allows the detection of a single dose of the drug of 200 mg/kg, but can be improved.     

Production and certification of an enzyme reference material for gamma-glutamyltransferase (CRM 319). Part 2: Certification campaign

We describe the process of certification for a gamma-glutamyltransferase reference material (CRM no. 319). Fifteen laboratories participated to this interlaboratory evaluation. All steps of the measurements were controlled in an effort to locate potential sources of variations. In particular, the exclusion of some data was strictly documented or justified by the non-observance of the IFCC method and (or) discrepancies in instrumentation, reconstitution of the lyophilized samples, or measurement technique. Inaccuracy in the reconstitution of the lyophilized material was +/- 0.68%, and the molar absorptivity of the 5-amino-2-nitrobenzoate reported by each laboratory was within +/- 2% limits of the value reported by the IFCC. Calculated from the sets of accepted results, the total CV among samples was 2.6% and the overall CV was 3.2%. Within-day and between-day CVs were 1.1% and 1.4%, respectively. The greatest variation for a single component was the between-laboratory variability (CV 3.1%); the within-laboratory CV, including the day effect, was 1.8%. Finally, the certified value for the catalytic concentration of this enzyme in the reconstituted lyophilized reference material was 86.8 U/L with an uncertainty of +/- 2.1 U/L (0.95 confidence interval). The uncertainty appeared to be compatible with the end-use of this reference material.     

The role of the nurse in active euthanasia and physician-assisted suicide

The researchers wanted to obtain insight into the cooperation between physicians and nurses with regard to active euthanasia and physician-assisted suicide (EAS). In study I a stratified random sample of 203 clinical specialists, 152 general practitioners (GPs) and 50 nursing home physicians (NHPs) participated. In study II a random sample of 521 GPs was drawn from the province of North Holland and a random sample of 521 GPs was drawn from the rest of the Netherlands. For study III all NHPs were approached. Data were collected by means of an interview in study I. In studies II and III an anonymous, postal questionnaire was used. Approximately half of the GPs did not consult with nurses about a patient's request for EAS, the intention to administer EAS, and the actual administration. In 5% of cases, the NHPs and the specialists did not consult with nurses concerning these aspects. The GPs and NHPs indicated in 4% and 3% of the cases, respectively, that nurses administered the lethal drug(s) to the patients; the corresponding figure for the specialists was 21%. Almost all GPs and NHPs and about three-quarters of the specialists thought that nurses should never be allowed to administer EAS.     

Severe pulmonary hypertension reversed by antibiotics in a patient with Whipple's disease

The case is described of a 58 year old man with systemic Whipple's disease with pericardial and pleural effusions and severe pulmonary hypertension. After three months of antibiotic treatment there was a complete resolution, not only of the symptoms known to be associated with Whipple's disease (diarrhoea, arthralgia, pericardial and pleural effusions), but also of pulmonary hypertension.