Jean-Jacques Legros

Hemodynamic changes induced by laparoscopy and their endocrine correlates: effects of clonidine

OBJECTIVESnWe investigated endocrine correlates of the hemodynamic changes induced by carbon dioxide pneumoperitoneum (PNO). We then studied whether clonidine might modulate the hemodynamic changes induced by PNO by reducing release of catecholamines and vasopressin.nnnBACKGROUNDnBoth mechanical and neurohumoral factors contribute to the hemodynamic changes induced by carbon dioxide PNO. Several mediators have been proposed, but no study has correlated hemodynamic changes with changes in levels of these potential mediators.nnnMETHODSnWe conducted two studies, each including 20 healthy patients scheduled for elective laparoscopic cholecystectomy. In the first study serial measurements of hemodynamics (thermodilution technique) were done during laparoscopy and after exsufflation. Plasma concentrations of cortisol, catecholamines, vasopressin, renin, endothelin and prostaglandins were measured at the same time points. In the second study patients were randomly allocated to receive 8 microg/kg clonidine infused over 1 h or placebo before PNO. Hemodynamics and plasma levels of cortisol, catecholamines and vasopressin were measured during PNO and after exsufflation.nnnRESULTSnPeritoneal insufflation resulted in a significant reduction of cardiac output (18+/-4%) and increases in mean arterial pressure (39+/-8%) and systemic (70+/-12%) and pulmonary (98+/-18%) vascular resistances. Laparoscopy resulted in progressive and significant increases in plasma concentrations of cortisol, epinephrine, norepinephrine and renin. Vasopressin plasma concentrations markedly increased immediately after the beginning of PNO (before PNO 6+/-4 pg/ml; during PNO 129+/-42 pg/ml; p < 0.05). The profile of vasopressin release paralleled the time course of changes in systemic vascular resistance. Prostaglandins and endothelin did not change significantly. Clonidine significantly reduced mean arterial pressure, heart rate and the increase in systemic vascular resistance. Clonidine also significantly reduced catecholamine concentrations but did not alter vasopressin and cortisol plasma concentrations.nnnCONCLUSIONSnVasopressin and catecholamines probably mediate the increase in systemic vascular resistance observed during PNO. Clonidine before PNO reduces catecholamine release and attenuates hemodynamic changes during laparoscopy.

Two years of replacement therapy in adults with growth hormone deficiency

Although several studies have shown beneficial short‐term effects of recombinant human growth hormone (rhGH) therapy in adult GH deficient (GHD) patients, few data are available on large groups of patients treated for more than one year. In addition, the optimal dose of rhGH for each patient and the baseline parameters that predict which patients will benefit most from therapy or will have adverse events are not entirely elucidated.

Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in parathyroids, enteropancreatic endocrine tissues, anterior pituitary, and other tissues. The gene for MEN1 has recently been cloned and shown to code for a 610‐amino acid protein of enigmatic function which probably acts as a tumor suppressor. Several mutations causing the MEN1 phenotype have been recently identified. In order to determine the spectrum of MEN1 gene mutations in a sample of 25 Belgian patients, we have systematically screened the 10 exons and adjacent sequences of the MEN1 gene by means of an automatic sequencing protocol. Twelve different mutations were identified including nonsense, frameshift, splicing, and missense mutations. Two of these mutations (D172Y and 357del4) occurred more than once. A missense mutation was also found in a kindred with familial hyperparathyroidism. We observed no significant correlation between the nature or position of mutation and the clinical status. We have also detected 6 intragenic polymorphisms and DNA sequence variants and have analyzed their frequencies in our population. Hum Mutat 13:54–60, 1999.

SUPPRESSED PROLACTIN BUT NORMAL NEUROPHYSIN LEVELS IN CIGARETTE SMOKING BREAST‐FEEDING WOMEN

The hormonal responses to breast‐feeding were studied during the first 3 post‐partum weeks in ten women smoking more than fifteen cigarettes/day and in a control group. Basal PRL levels were significantly lower in smokers compared with non‐smokers, but suckling induced acute increments in serum PRL and oxytocin‐linked neurophysin, which were not influenced by smoking. The lactational pattern was normal, but smokers weaned their babies significantly earlier compared with non‐smokers. Heavy cigarette smoking women have lower basal PRL levels and this may shorten the period of lactation.

THE EFFECT OF HYPOTHALAMIC LUTEINIZING HORMONE RELEASING HORMONE (LH‐RH) ON PLASMA GONADOTROPHIN LEVELS IN NORMAL SUBJECTS

The release of gonadotrophin following the injection of synthetic LH‐RH (Hoechst) was studied in various physiological and experimental circumstances.

NEUROPHYSINS IN CENTRAL DIABETES INSIPIDUS

When they were discovered by Acher and co-workers, neurophysins were thought to act as carriers for the active nonapeptides vasopressin (AVP) and oxytocin (OT) and were then recognized as the inactive fragment of a precursor with a higher molecular weight (propressophysin). The role of neurophysins in the hypothalamo-neurohypophyseal system is now being reconsidered in the light of crystallographic and molecular biology research and the recent definition of the different deletions or substitutions that cause central diabetes insipidus in rats (Brattleboro) or human beings. Apparently, any disruption of the structure and/or conformation of neurophysins (by genic substitution or deletion) may cause a decline in the binding and the activity of the endopeptidase responsible for the cleavage of the AVP. The disruption may also produce a change in the polymerization of neurophysins and salt bridges relating this to the neuropeptides, with the result that there is an accelerated aspecific enzymatic degradation of the hormone revealing clinical symptomatology. So, rather than being a mere inactive part of the precursor, neurophysins are now equally regarded as a system for carrying and protecting nonapeptides.

Pathogenic Tracks in Fatigue Syndromes

This review analyses the recent literature devoted to two related fatigue syndromes: chronic fatigue syndrome (CFS) and acute onset postviral fatigue syndrome (PVFS). The articles are grouped into five pathogenic tracks: infectious agents, immune system, skeletic muscle, hypothalamo-pituitary-adrenal (HPA) axis and psychiatric factors. Although a particular infectious agent is unlikely to be responsible for all CFS cases, evidence is shown that host-parasite relationships are modified in a large proportion of patients with chronic fatigue. Antibody titres against infectious agents are often elevated and replication of several viruses could be increased. Chronic activation of the immune system is also observed and could be due to the reactivation of persistent or latent infectious agents such as herpes viruses (i.e. HHV-6) or enteroviruses. It could also be favorised by an impaired negative feedback of the HPA axis on the immune system. A model is proposed where the abnormalities of the HPA axis are primary events and are mainly responsible for a chronic activation of the immune system which in turn induces an increased replication of several viruses under the control of cellular transcription factors. These replicating viruses together with cytokines such as TNF-alpha would secondarily induce functional disorders of muscle and several aspects of asthenia itself.