Pulmonary edema in meningococcal septicemia associated with reduced epithelial chloride transport.

OBJECTIVES: To test the hypothesis that meningococcal septicemia-related pulmonary edema is associated with a systemic abnormality of epithelial sodium and chloride transport and to investigate an association with hormones regulating Na transport. DESIGN: Prospective observational study. SETTING: The 24-bed pediatric intensive care unit and pediatric wards of Royal Liverpool Children's Hospital. PATIENTS: Consecutive children admitted to the pediatric intensive care unit and pediatric wards with a diagnosis of meningococcal septicemia and children (controls) with noninfectious critical illness receiving ventilatory support in the pediatric intensive care unit. MEASUREMENTS AND MAIN RESULTS: We measured sweat and saliva electrolytes, renal electrolyte excretion, nasal potential difference, and aldosterone, thyroxine, and cortisol levels. Pulmonary edema was diagnosed by chest radiography and its severity quantified by calculation of ventilation index at admission and duration of mechanical ventilation. We recruited 17 patients with severe meningococcal septicemia (nine patients with pulmonary edema), 14 patients with mild meningococcal septicemia, and 20 controls. Sweat and saliva Na and Cl concentrations and renal Na excretion were significantly (p < .05) higher in patients with pulmonary edema compared with controls. Nasal potential difference and amiloride response in patients with pulmonary edema were not significantly different to controls, but response to a low Cl solution was reduced in the nasal airway of patients with pulmonary edema (p < .05). Sweat and saliva chloride concentrations correlated significantly and better with ventilation index and duration of ventilation than sodium concentrations. Aldosterone, thyroxine, and cortisol levels were not significantly different between groups. CONCLUSIONS: We have confirmed that meningococcal septicemia-related pulmonary edema is associated with reduced systemic sodium and chloride transport. Features of reduced Cl transport were most closely associated with markers of respiratory compromise, and this was supported by the reduced chloride channel function detected on nasal potential difference measurement.

Effects of supra-physiological changes in human ovarian hormone levels on maximum force production of the first dorsal interosseus muscle.

The purpose of this study was to investigate the effects of supra-physiological changes in ovarian hormone levels on maximum force production in two conditions, one physiological (pregnancy) and one pseudo-physiological (in vitro fertilization (IVF) treatment). Forty IVF patients were tested at four distinct stages of treatment and 35 women were tested during each trimester of pregnancy and following parturition. Maximum voluntary isometric force per unit cross-sectional area of the first dorsal interosseus muscle was measured. Plasma concentrations of total and bioavailable oestradiol and testosterone were measured, in addition to the total concentrations of progesterone and human chorionic gonadotropin. Despite significant changes in the concentrations of total progesterone, 17beta-oestradiol, bioavailable oestradiol and testosterone between phases, strength did not change significantly throughout IVF treatment (1.30+/-0.29, 1.16+/-0.38, 1.20+/-0.29 and 1.26+/-0.34 N mm-2, respectively, in the 4 phases of IVF treatment). Force production was significantly higher during the second trimester of pregnancy than following childbirth (1.33+/-0.20 N mm-2 at week 12 of pregnancy, 1.51+/-0.42 N mm-2 at week 20, 1.15+/-0.26 N mm-2 at week 36 and 0.94+/-0.31 N mm-2 at week 6 postnatal) but was not significantly correlated with any of the hormones measured. These data suggest that extreme changes in the concentrations of reproductive hormones do not affect the maximum force-generating capacity of young women.

Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men.

BACKGROUND: Conflicting views are reported on the association between advancing age and gradually diminishing concentrations of serum total testosterone in men. The putative loss of diurnal rhythm in serum total testosterone in older men is reported to be in part due to low concentrations in the morning when compared to concentrations found in young men. We have measured total, free and bioavailable testosterone along with SHBG in samples taken every 30 min throughout a 24-h period in 10 young and eight middle-aged men. RESULTS: Both young and middle-aged men displayed a significant diurnal rhythm in all variables, with a minimum fall of 43% in total testosterone from peak to nadir in all subjects. Subjecting the data to a time series analysis by least squares estimation revealed no significant difference in mesor (P = 0.306), amplitude (P = 0.061) or acrophase (P = 0.972) for total testosterone between the two groups. Comparing bioavailable testosterone in the two groups revealed no significant difference in mesor (P = 0.175) or acrophase (P = 0.978) but a significant difference (P = 0.031) in amplitude. Both groups display a significant circadian rhythm (middle-aged group P < 0.001; young group P = 0.014). Free testosterone revealed a highly significant rhythm in both the young group (P < 0.001) and the middle-aged group (P = 0.002), with no significant difference between the groups in mesor (P = 0.094) or acrophase (P = 0.698). Although analysis of the SHBG data revealed a significant rhythm in the young group (P = 0.003) and the older group (P < 0.001), the acrophase occurred in the mid afternoon in both groups (15.12 h in the young and 15.40 h in the middle-aged). The older men had a significantly greater amplitude (P = 0.044) but again no significant difference was seen in mesor (P = 0.083) or acrophase (P = 0.477) between the two groups. Acrophases for total, bioavailable and free testosterone occurred between 07.00 h and 07.30 h; for SHBG the acrophase occurred at 15.12 h in the young group and 15.40 h in the middle-aged group. CONCLUSIONS: The study suggests that the diurnal rhythm in these indices of androgen status is maintained in fit, healthy men into the 7th decade of life.

Assessment of adrenal function in the initial phase of meningococcal disease.

OBJECTIVE: To determine the status of the hypothalamic-pituitary-adrenal axis in children who had meningococcal disease and were admitted to 2 regional pediatric intensive care units. METHODS: Sixty-five children (34 boys; median age: 2.5 years; range: 0.2-15 years) had cortisol and adrenocorticotropic hormone (ACTH) levels measured on admission, then at 8 AM and 8 PM during the next 48 hours. At 48 hours, a low-dose short Synacthen test (LDST) (500 ng of 1-24 corticotropin/m2) was performed in 42 patients (19 boys). Normal ranges for 8 AM cortisol and ACTH levels in unstressed children were 140 to 500 nmol/L and 2 to 11.3 pmol/L, respectively. Adrenal insufficiency (AI) was defined as a peak cortisol <500 nmol/L on the LDST or an 8 AM cortisol value <140 nmol/L. RESULTS: Five (7.7%) of the 65 children died, including 1 with primary AI. Cortisol levels were elevated on admission (median: 1122 mmol/L; range: 65-2110 nmol/L) with 81% of values more than the 8 AM normal range. The median ACTH level on admission was within the 8 AM normal range, but 40% of values were more than the 8 AM normal range. However, 7% and 8% of cortisol and ACTH values, respectively, were less than the normal range. Both cortisol and ACTH levels fell thereafter and showed no diurnal variation during the 48-hour profile. Six (14%) of the 42 failed the LDST. These patients had significantly lower mean 8 AM cortisol values than those with a normal peak value on the LDST. Five additional patients who did not have the LDST had 8 AM cortisol values <140 nmol/L. In the diagnosis of AI, the sensitivity of the 8 AM mean cortisol value at a cutoff of 400 nmol/L, judged against the LDST, was 83%; the specificity was 81%. CONCLUSIONS: During the initial phase of meningococcal disease, raised cortisol and ACTH levels indicate an appropriate stress response within the hypothalamic-pituitary-adrenal axis. However, a substantial subpopulation (11 [16.9%] of 65) has evidence of adrenal dysfunction during this period. Morning cortisol values in the initial phase of meningococcal disease could be used as a potential early index of AI.