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.     

New ways of performing in vivo flow velocity measurements in the basilar artery

The basilar artery is the only large artery in which two flows merge, and this is reflected in the flow downstream. We report quantitative flow — velocity measurements with a phase-based MR technique, i.e. the Fourier velocity encoding method, in the basilar artery of a volunteer. To our knowledge, this has not previously been performed successfully. A comparison is made with the results of flow velocity measurements in the basilar artery with transcranial Doppler ultrasonography; the techniques agreed very well. Although Doppler ultrasonography is still most widely used, no information on the flow rate and the flow velocity distribution in the basilar artery can be provided. MR flow measurement techniques appear promising when detailed information on the flow velocity distribution and flow rate is needed.     

Lipid-associated total parenteral nutrition in patients with severe acute pancreatitis

Biochemical data were studied in 18 patients with severe acute pancreatitis receiving lipid associated with total parenteral nutrition. The mean nonprotein energy intake was 30 kcal/kg/day, with 34-70% of the nonprotein calories as lipid. These parameters were no different between patients who survived and those who died. The mean sum of Ranson criteria was significantly higher in patients who died as compared with those who survived. Plasma triglycerides, glucose, albumin, and the amount of insulin supplementation were related to the severity of the disease and to the outcome. Persistent hypertriglyceridemia, hyperglycemia, hypoalbuminemia, and higher insulin requirements were observed in patients who died in comparison with those who survived and this appeared to be an index of fatal outcome. These abnormalities reflect in part an inability to utilize nonprotein energy, because the measured energy expenditure in relation to intake was lower in the patients who died, despite comparable intakes and expected energy expenditures.     

Coronary artery and saphenous vein graft remodeling: A review of histologic findings after various interventional procedures—part V

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effect on the site of obstruction has been termed “remodeling.” Part V of this six-part series focuses on remodeling effects of balloon angioplasty on obstructed young (≤ 1 year) and old (> 1 year) saphenous vein bypass grafts.     

Dependence of vitamin B-6 status assessment on alcohol intake among elderly men and women (Dutch Nutrition Surveillance System)

To obtain more insight into the effect of moderate alcohol intake on vitamin B-6 status indicators, we studied the associations of alcohol intake (unadjusted and adjusted for intake of vitamin B-6 and protein) with the erythrocyte aspartate aminotransferase activation coefficient (EAST-AC) and plasma pyridoxal 5'-phosphate (PLP) level. Data obtained from men (n = 224) and women (n = 217) aged 65-79 (nationwide sample in the Netherlands) were used for this purpose. Although alcohol intake (a maximum of 21% of the energy came from alcohol) tended to be positively associated with PLP, this association never reached statistical significance (p greater than or equal to 0.05). EAST-AC was inversely associated with alcohol intake, whether or not it was adjusted for vitamin B-6 and protein intake. Similar results were found for the total EAST activity (after adding PLP) or apoenzyme activity; the basal EAST activity (before adding PLP) or holoenzyme activity was not associated with the alcohol intake. These results indicate that caution is needed in the interpretation of the specificity of EAST-AC (i.e., the degree to which EAST-AC is unaffected by other factors) as an indicator of vitamin B-6 intake.     

Positive tip cultures and related risk factors associated with intravascular catheterization in pediatric cardiac patients

The incidence and risk factors of positive catheter tip cultures were studied prospectively in 392 consecutive children undergoing cardiac surgery under cover of cephalothin prophylaxis. A total of 1649 catheter tips were cultured and 58 (3.5%) yielded positive cultures. Specifically, the incidence of positive catheter tip cultures for iv, central venous, arterial and pulmonary arterial (PA) catheters was 0.9%, 5.9%, 3.9% and 10.6%, respectively, whereas one of the six surgically placed venous and arterial catheters had a positive tip culture and none of the 279 transthoracic catheters. Staphylococcus epidermidis was isolated from 79% of the positive tip cultures. Ten percent of the children had one or more positive tip cultures but none developed catheter-related septicemia or endocarditis. Stepwise logistic regression analysis revealed that longer in situ time (p less than .001), younger age (p less than .001), and inotropic support (p = .003) were significant independent predictors of risk for children developing positive catheter tip cultures. The safe in situ period for arterial, central venous, and PA catheters is 3 days in infants under 1 yr and 4 and 6 days for arterial and central venous catheters, respectively, in older children, if 0.95 cumulative probability of remaining free of a positive tip culture is accepted. The data generally support the bacteriologic safety of invasive hemodynamic monitoring in infants and children undergoing cardiac surgery.     

Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph-negative,BCR-positive patients with chronic myeloid leukemia

Leukemic cells from two patients with Philadelphia-negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M-BCR region and formation of BCR-ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR-ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph-positive CML and in almost all investigated CML with variant Ph or Ph-negative, BCR-positive cases. The few aberrant chromosomal localizations of BCR-ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR-ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph-negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley-Liss, Inc.     

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.