ABSTRACT
OBJECTIVES: Diminished GH response to stimulation has been demonstrated in obesity, leading to erroneous diagnosis of GH deficiency. The aim of this study was to evaluate the influence of body mass index (BMI) on GH responsiveness in patients at risk for pituitary function deficits. METHODS: A total of 59 healthy subjects and 75 patients with a pituitary insult underwent insulin tolerance test or pyridostigmine+GHRH test in order to assess GH secretory reserve. Normal subjects and patients were classified as normal weight (BMI <24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI >30 kg/m(2)). RESULTS: All normal individuals with BMI <24.9 kg/m(2) demonstrated adequate GH responses, while three of the 21 overweight (14.3%) and nine of the 28 obese subjects (32.1%) did not respond to GH stimulation. Among patients, four of 14 (28.6%) with BMI <24.9 kg/m(2), 18 of 22 (81.8%) who were overweight, and 28 of 39 (71.7%) who were obese did not respond to GH stimulation. Of the 46 nonresponder patients with increased BMI, nine (19.6%) had normal insulin-like growth factor 1 (IGF1) values and no other pituitary hormone deficits, raising questions about the accuracy of somatotroph function assessment, while all nonresponders with BMI <24.9 kg/m(2) had low IGF1 values and panhypopituitarism. CONCLUSIONS: Our results indicate that BMI >25 kg/m(2) has a negative effect on GH response not only in normal healthy subjects but also in patients at risk for pituitary function deficit as well. Parameters such as IGF1 levels and anterior pituitary deficits should be taken into account to accurately assess GH status in these patients.
Subject(s)
Body Mass Index , Human Growth Hormone/blood , Human Growth Hormone/deficiency , Pituitary Diseases/blood , Pituitary Diseases/diagnosis , Pituitary Gland/metabolism , Adolescent , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Obesity/blood , Obesity/complications , Obesity/diagnosis , Overweight/blood , Overweight/complications , Overweight/diagnosis , Pituitary Diseases/complications , Risk Factors , Young AdultABSTRACT
BACKGROUND: Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R) complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity. RESULTS: Using an in vitro model of SPW-R activity we found that thiopental (50-200 muM) significantly and concentration-dependently reduced the incidence of SPW-R events (it increased the inter-event period by 70-430 %). At the concentration of 25 muM, which clinically produces mild sedation and explicit memory impairment, thiopental significantly reduced the quantity of ripple oscillation (it reduced the number of ripples and the duration of ripple episodes by 20 +/- 5%, n = 12, P < 0.01), and suppressed the rhythmicity of SPWs by 43 +/- 15% (n = 6, P < 0.05). The drug disrupted the synchrony of SPWs within the CA1 region at 50 muM (by 19 +/- 12%; n = 5, P < 0.05). Similar effects of thiopental were observed at higher concentrations. Thiopental did not affect the frequency of ripple oscillation at any of the concentrations tested (10-200 muM). Furthermore, the drug significantly prolonged single SPWs at concentrations >/=50 muM (it increased the half-width and the duration of SPWs by 35-90 %). Thiopental did not affect evoked excitatory synaptic potentials and its results on SPW-R complexes were also observed under blockade of NMDA receptors. Phenobarbital significantly accelerated SPWs at 50 and 100 muM whereas it reduced their rate at 200 and 400 muM. Furthermore, it significantly prolonged SPWs, reduced their synchrony and reduced the quantity of ripples only at the clinically very high concentration of 400 muM, reported to affect memory. CONCLUSION: We hypothesize that thiopental, by interfering with SPW-R activity, through enhancement of the GABAA receptor-mediated transmission, affects memory processes which involve hippocampal circuit activation. The quantity but not the frequency of ripple oscillation was affected by the drug.
Subject(s)
Hippocampus/drug effects , Hippocampus/physiopathology , Memory Disorders/chemically induced , Memory Disorders/physiopathology , Phenobarbital/pharmacology , Thiopental/pharmacology , Action Potentials/drug effects , Action Potentials/physiology , Anesthetics, Intravenous/pharmacology , Animals , Anticonvulsants/pharmacology , Biological Clocks/drug effects , Biological Clocks/physiology , Dose-Response Relationship, Drug , GABA-A Receptor Agonists , Male , Memory/drug effects , Memory/physiology , Nerve Net/drug effects , Nerve Net/physiopathology , Neural Pathways/drug effects , Neural Pathways/physiopathology , Organ Culture Techniques , Rats , Rats, Wistar , Receptors, GABA-A/metabolism , Synaptic Transmission/drug effects , Synaptic Transmission/physiologyABSTRACT
BACKGROUND: A regimen including interferon-alpha has become the standard of care in the treatment of chronic hepatitis C over the last decade. One rare adverse effect associated with the use of interferon-alpha is a granulomatous pulmonary reaction. CASE: A unique case of uterine sarcoidosis associated with the use of interferon-alpha for chronic hepatitis C infection is presented. CONCLUSION: Gynecologists should be aware of a potential association between interferon-alpha therapy and granulomatous reactions occurring not only in the lung but also in the female genital tract.
