Non-musculoskeletal symptoms in joint hypermobility syndrome. Indirect evidence for autonomic dysfunction?

SIR, Joint hypermobility syndrome (JHS) is a chronically disablingdisorder manifested as widespread pain, fatigue, multiple softtissue lesions and fragility of skin and supportive connectivetissues [1]. It is a condition that is often overlooked by clinicians[2]. Moreover, clinical experience suggests that previouslyunrecognized non-musculoskeletal symptoms, including presyncope,palpitations and bowel disturbance, are also common in JHS.Recent evidence demonstrates dysfunction of the autonomic nervoussystem as an explanation for these symptoms [3]. Recognitionof these symptoms by clinicians     

The syndrome of inappropriate secretion of antidiuretic hormone and fluid restriction in meningitis--how strong is the evidence?

In patients with meningitis, fluid restriction is recommended to counter the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and to reduce cerebral oedema. However, any effects of an increased plasma level of ADH upon cerebral oedema would be due not to fluid retention but to hypoosmolality. In a literature review of fluid and electrolyte disturbances and the effect of fluid therapy in bacterial/tuberculous meningitis, the prevalence of hyponatraemia, hypoosmolality and SIADH varied considerably; apparently, non-osmotic stimuli for the secretion of ADH, e.g. intracranial hypertension and hypovolaemia, were present in most patients. Neither clinical nor experimental studies have confirmed that fluid restriction reduces the cerebral oedema in meningitis. Furthermore, compared with maintenance therapy, fluid restriction did not improve outcome in a randomized controlled study. Thus, we find no evidence to support the use of fluid restriction in patients with meningitis. Fluid therapy in acute bacterial meningitis should aim at avoiding hypovolaemia and hypoosmolality based on the assumptions that (i) ADH is increased by non-osmotic stimuli; (ii) elevated ADH is less important for cerebral oedema than severe hypoosmolality, which may in itself induce or aggravate oedema; (iii) maintenance fluid therapy aiming at isoosmolality will not worsen neurological outcome; and (iv) hypovolaemia is difficult to detect, and detrimental for cerebral perfusion, in these patients.     

Hormone use and abuse: what is the difference between hormones as fountain of youth and doping in sports?

GH can induce changes in body composition that are considered to be advantageous to aging subjects especially. However, there are no results indicating that the use of GH during aging should be advocated, because of the lack of any proven efficacy for whatever parameter. Also, data indicate that calorie restriction can extend life spans by altering the rate of decline in reserve capacity as well as by reducing the cumulative exposure to GH. Moreover, animal data suggest that lower GH actions are positively correlated with longevity. The abuse of GH by sportsmen is based on the belief that it has potent anabolic effects, while it is difficult to detect the abuse. Again, this supposed efficacy cannot be supported by any scientific data.     

Secondary prevention of ischemic cerebrovascular disease. What is the evidence?

Patients who had a transient ischemic attack or stroke are at increased risk of experiencing recurrent cerebrovascular events. For this reason, secondary prevention of ischemic cerebrovascular disease is essential. Several modifiable, lifestyle-associated risk factors have been implicated, such as physical activity, smoking, and alcohol consumption. Established and emerging vascular risk factors are associated with an increased risk of stroke. Pharmacologic treatment, including the use of antiplatelet, antihypertensive, and lipid-lowering agents, has also been shown to reduce the risk of secondary cerebrovascular events. Surgical intervention, either open or endovascular, may be the preferred therapeutic option in well-defined subsets of patients. It is important to establish specific measures for the early detection and prevention of recurrent cerebrovascular disease. Therefore, further research and greater awareness in this field are needed.     

Indirect costs for medical education. Is there a July phenomenon?

Medicare currently pays for "indirect costs" of medical education to support the higher costs of care in teaching hospitals. To investigate whether indirect costs are higher earlier in the training year when house officers might be less efficient--the "July phenomenon"--we compared utilization by 1251 patients hospitalized during July and August with 1338 patients hospitalized during April and May from 1982 through 1984 at Brigham and Women's Hospital, Boston, Mass. These included all patients in the 10 most prevalent medical and surgical diagnosis related groups. Using analysis of covariance to correct for age, sex, diagnosis related group, urgency of admission, temporal change, and mortality, we found no differences in length of stay, total charges, or categories of ancillary charges. These results suggest that there is no substantial increase in the cost of care early in the training year; there was no evidence of a "July phenomenon."     

Clinical evidence of growth hormone for patients undergoing abdominal surgery： Meta-analysis of randomized controlled trials

AIM: To assess the effectiveness and safety of perioperative growth hormone (GH) in patients undergoing abdominal surgery. METHODS: We searched the following electronic databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Chinese Bio-medicine Database. The search was undertaken in February 2003. No language restrictions were applied. Randomized controlled trials (RCT) comparing GH with placebo in patients undergoing abdominal surgery were extracted and evaluated. Methodological quality was evaluated using the Jadad scale. RESULTS: Eighteen trials involving 646 patients were included. The combined results showed that GH had a positive effect on improving postoperative nitrogen balance (standardized mean difference [SMD] = 3.37, 95%CI [2.46, 4.27], P<0.00001), and decreasing the length of hospital stay (weighted mean difference [WMD] = -2.07, 95%CI [-3.03, -1.11], P= 0.00002), and reducing the duration of postoperative fatigue syndrome (SMD = -1.83, 95%CI [-2.37, -1.30], P<0.00001), but it could increase blood glucose levels (WMD = 0.91, 95%CI [0.56, 1.25], P<0.00001). CONCLUSION: GH for patients undergoing abdominal surgery is effective and safe, if blood glucose can be controlled well. Further trials are required with a sufficient size to account for clinical heterogeneity and to measure other important outcomes such as infection, morbidity, mortality, fluid retention, immunomodulatory effects, and tumor recurrence.     

Does cortisol mediate endotoxin-induced inhibition of pulsatile luteinizing hormone and gonadotropin-releasing hormone secretion?

Bacterial endotoxin (lipopolysaccharide), a commonly used model of immune/inflammatory stress, inhibits reproductive neuroendocrine activity and concurrently induces a profound stimulation of the hypothalamo-pituitary-adrenal axis. We employed two approaches to test the hypothesis that enhanced secretion of cortisol mediates endotoxin-induced suppression of pulsatile GnRH and LH secretion in the ovariectomized ewe. First, we mimicked the endotoxin-induced increase in circulating cortisol by delivering the glucocorticoid in the absence of the endotoxin challenge. Within 1-2 h, experimentally produced increments in circulating cortisol suppressed pulsatile LH secretion in a dose-dependent fashion. Second, we blocked the endotoxin-induced stimulation of cortisol secretion using the drug metyrapone, which inhibits the 11-beta hydroxylase enzyme necessary for cortisol biosynthesis. In the absence of a marked stimulation of cortisol secretion, endotoxin still profoundly inhibited pulsatile GnRH and LH secretion. We conclude that, although enhanced cortisol secretion may contribute to endotoxin-induced suppression of reproductive neuroendocrine activity, the marked stimulation of the glucocorticoid is not necessary for this response. Our findings are consistent with the hypothesis that immune/inflammatory stress inhibits reproductive neuroendocrine activity via more than one inhibitory pathway, one involving enhanced secretion of cortisol and the other(s) being independent of this glucocorticoid.     

Drug-induced syndrome of inappropriate diuresis or of antidiuretic hormone secretion?

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (Bartter and Schwartz, 1967) is defined as low effective plasma osmolality due to impaired renal water dilution together with impaired thirst center regulation once effective hypovolemia and corticotropin deficiency are ruled out (Robertson, 2006).Impaired water dilution is encountered following stimulation of voloreceptors triggering ADH (i.e., vasopressin) secretion through brain circumventricular organ stimulation [including notably the subfornical organ (SFO)] (Bichet, 2019). This condition is reversed as soon as volemia is restored: hyponatremia is corrected within hours, unlike withdrawal of drugs inducing SIADH, in which optimal water dilution recovery usually takes several days or weeks. Therefore, diuretics will be beyond the scope of this review.