Audit of the management of spontaneous pneumothorax.

This audit suggests that clinical practice in the management of spontaneous pneumothorax differs from guidelines issued by the British Thoracic Society. In particular simple aspiration was attempted in only seven out of 65 patients and clamping of an intercostal chest drain occurred in 12 out of 50 cases. Junior medical staff require more training in intercostal drainage.

Role of estrogen deficiency in pathogenesis of secondary hyperparathyroidism and increased bone resorption in elderly women.

Whether the increased bone resorption and secondary hyperparathyroidism in elderly women is due to aging or to estrogen deficiency is unclear. To address this issue, we measured serum intact parathyroid hormone (PTH) and biochemical markers in serum and urine samples from 30 premenopausal women (32 +/- 0.5 years, mean age +/- SE), 30 estrogen-deficient postmenopausal women (74.2 +/- 0.6 years), and 30 elderly women (73.8 +/- 0.6 years) receiving long-term estrogen treatment. Because of the first and third groups were comparable in estrogen status but not in age, whereas the second and third groups were comparable in age but not in estrogen status, the independent effects of age and estrogen deficiency could be assessed quantitatively. Mean values were higher in the estrogen-deficient postmenopausal women than in the premenopausal women for serum PTH (by 33%, p < .01) and for bone resorption markers [by 50% p < .001) for urine cross-linked N-teleopeptide of type I collagen (NTx); 34% (p < .001) for urine pyridinoline (Pyd); and 36% (p < .001) for urine deoxypyridinoline (Dpd)]. However, mean values for serum PTH in the postmenopausal women receiving estrogen treatment did not differ from those in the premenopausal women, and mean values for bone resorption markers were not different (urine NTx and Pyd) or were lower [urine Dpd, by -12%, (p < .005)]. These findings suggest that late consequences of estrogen deficiency rather than age-related processes per se are the principal causes of the secondary hyperparathyroidism and increased bone resorption in elderly women.

Role of calcium intake in modulating age-related increases in parathyroid function and bone resorption.

Serum parathyroid hormone (PTH) and bone resorption increase in elderly women and contribute to age-related bone loss. Whether these abnormalities are caused by calcium deficiency resulting from age-related decreases in absorption and renal conservation is unclear. We studied 28 normal elderly women (mean +/- SD, age 69.3 +/- 2.7 yr) who were maintained for 3 yr on usual calcium intake levels (20.4 +/- 7.2 mmol/day [815 +/- 289 mg/day]; n = 15) (known as the usual calcium group) or high calcium intake levels (60.4 +/- 6.5 mmol/day [2414+/260 mg/day]; n = 13) (known as the high calcium group) and a reference group of 12 normal young adult women (age 30.1 +/- 4.4 yr), whose calcium intake was 23.0 +/- 4.8 mmol/day (918 +/- 193 mg/day) (known as the young group). Serum PTH was measured every 2 h, and urinary excretion of deoxypyridinoline (Dpd), a new marker for bone resorption, was measured in 4 h collections. Parathyroid gland secretory capacity was assessed during induced hypocalcemia. The mean 24 h serum PTH was 40% lower (P < 0.001), and the mean 24 h urinary Dpd was 35% lower (P < 0.005) in the high than in the usual calcium group. Mean parathyroid gland secretory capacity also was 47% lower (P < 0.005) in the high calcium group than in the usual calcium group. However, the usual calcium group had a mean 24 h serum PTH level that was 70% higher (P < 0.001) and a mean 24 h urinary Dpd level that was 30% higher (P < 0.005) than the young group, whereas the high calcium group was indistinguishable from the young group. Thus, failure of elderly women to increase their calcium intake to offset age-related increases in calcium requirement contributes substantially to their development of increased parathyroid activity and increased bone resorption, whereas a high calcium intake can reverse both abnormalities.

Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause--a clinical research center study.

To assess the mechanism by which estrogen replacement therapy (ERT) enhances renal calcium conservation in perimenopausal women, we studied 18 normal women in early postmenopause before and after 6 months of ERT (cyclic treatment with transdermal estradiol at 100 micrograms/day and medroxyprogesterone acetate at 10 mg/day for the first 12 days of each cycle). The changes after ERT were: serum ionized calcium and ultrafiltrable calcium, no change; serum intact PTH, 38.2% increase (P < 0.0001); serum 1,25-dihydroxyvitamin D, 23.8% increase (P < 0.0001); urinary calcium excretion, 33.3% decrease (P < 0.001); and deoxypyridinoline (a marker for bone resorption), 19.5% decrease (P < 0.0001). Also, ERT increased tubular reabsorption of calcium (TRCa; 97.6% +/- 0.2% to 98.7% +/- 0.1%; P < 0.0001), and this increase correlated with that in serum PTH (r = 0.49; P < 0.05). After the infusion of human PTH-(1-34), the TRCa maximum was greater after ERT than at baseline (99.4% +/- 0.1% vs. 99.0% +/- 0.1%; P < 0.0001), resulting in decreased calcium excretion (0.9 +/- 0.20 vs. 1.43 +/- 0.20 mumol/dL glomerular filtrate; P < 0.001). Thus, in early postmenopause, the major mechanism of increased renal calcium conservation after ERT is an increase in TRCa due to an increase in serum PTH because of estrogen-induced inhibition of bone resorption. However, ERT also may directly increase the TRCa maximum in response to PTH.

Measurement of colony-stimulating factors in synovial fluid: potential clinical value.

In this study, 100 synovial fluid (SF) samples from patients with a variety of arthritides were assayed for levels of colony-stimulating factors (CSFs) using a human bone-marrow bioassay and enzyme immunoassays for granulocyte (G-) and granulocyte-macrophage (GM-) CSFs. GM-CSF was found more frequently in samples from rheumatoid arthritis (RA) subjects (49%) than in non-RA samples (29%). Absence of GM- but not G- or bioassay CSFs characterised samples from subjects with psoriatic arthritis and ankylosing spondylitis (n = 14). There was strong evidence of an antagonistic relationship between levels of G- and GM-CSFs in samples from RA patients, an effect independent of drug treatment. However, treatment with non-steroidal anti-inflammatory agents (NSAIDs) may affect reported CSF concentrations: G-CSF levels were significantly lower in samples from subjects not taking NSAIDs. These results suggest that SF-CSF estimations using commercially available assays could provide useful diagnostic clues for clinicians, but careful interpretation is warranted particularly in patients on long-term NSAID treatment.

Circulating levels of cytokines that modulate bone resorption: effects of age and menopause in women.

Interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are cytokines with potent bone-resorbing effects; some of these biologic effects are opposed by interleukin-1 receptor antagonist (IL-1ra). In vitro and animal model studies suggest that these cytokines are paracrine mediators of the increased bone resorption associated with estrogen deficiency, and increases in their production also could contribute to age-related bone loss. Therefore, we measured serum concentrations of these cytokines in 80 normal women who were 24-87 years old. IL-6 concentration correlated highly with age (p < 0.001) and increased three-fold during life. However, multiple-regression analysis showed no significant correlation between serum IL-6 levels and menopausal status, serum estradiol concentration, or markers for bone turnover (serum bone alkaline phosphatase, osteocalcin, carboxyl-terminal telopeptide of type I collagen, or 24 h urinary free pyridinoline excretion). Serum IL-1 alpha, IL-1 beta, or IL-1ra level did not change with age and, by multiple-regression analysis, did not correlate with markers of bone turnover, except IL-1ra weakly with ICTP. We found no relationship between bone-resorbing cytokines and ovarian function. Although the large age-related increase in serum IL-6 concentration could contribute to age-related bone loss, the lack of correlation with markers for bone turnover argues against this. However, based on the strong evidence in experimental animals that these cytokines are involved in estrogen action on bone, further studies in humans are warranted.

Resting energy expenditure in chronic cardiac failure.

1. Resting energy expenditure has previously been shown to be elevated in the acute phase of heart failure, but the situation in the compensated state of chronic cardiac failure is unclear. Resting energy expenditure was assessed in 14 patients with stable chronic cardiac failure and 14 matched control subjects by using indirect calorimetry. 2. Resting energy expenditure was significantly elevated in the patients with chronic cardiac failure (112.6 +/- 18.1 versus 87.1 +/- 12.2 kJ day-1 kg-1 total body weight, P less than 0.0002; mean +/- SD) as were resting O2 consumption (3.88 +/- 0.64 versus 3.00 +/- 0.43 ml min-1 kg-1, P less than 0.0002), ventilation (164 +/- 40.3 versus 104 +/- 16.2 ml min-1 kg-1, P less than 0.0001) and heart rate (85.8 +/- 16.9 versus 66.6 +/- 6.9 beats/min, P less than 0.001). Both the resting plasma concentration of noradrenaline (4.48 +/- 1.52 versus 2.28 +/- 0.96 nmol/l, P less than 0.0001) and the serum concentration of free fatty acids (0.78 +/- 0.21 versus 0.57 +/- 0.27 mmol/l, P less than 0.03) were greater in the patients with chronic cardiac failure. Analysis of covariance indicated that most of the difference in resting energy expenditure could be accounted for by the elevated ventilation in the patients with chronic cardiac failure. Arm muscle area, an index of wasting, was lower in the patients with chronic cardiac failure (39.1 +/- 13.1 versus 50.5 +/- 9.4 cm2, P less than 0.02) and resting energy expenditure was found to account for some of this difference. 3. We conclude that an elevated basal metabolism occurs in chronic cardiac failure.(ABSTRACT TRUNCATED AT 250 WORDS)

The assessment of hepatic and peripheral insulin sensitivity in hypertriglyceridemia.

Peripheral insulin resistance is a common finding in hypertriglyceridemia. However, hepatic insulin sensitivity has rarely been investigated. We measured hepatic and peripheral insulin sensitivity in eight nondiabetic, nonobese hypertriglyceridemic subjects (HT) with raised triglyceride concentrations (4.3 +/- 0.6 mmol.L-1, mean +/- SEM) and eight age-, sex-, and weight-matched control subjects (C) with normal triglyceride concentrations (1.2 +/- 0.2 mmol.L-1). Insulin secretion was assessed during a 75-g oral glucose tolerance test (OGTT). Glucose turnover was determined using 3(3H) glucose in the postabsorptive state and during euglycemic glucose clamps at insulin infusion rates of 0.25 and 1.0 mU.kg-1.min-1. At identical fasting glucose concentrations (HT, 5.2 +/- 0.2; C, 5.2 +/- 0.2 mmol.L-1), the glucose responses to OGTT were similar in both groups. Fasting plasma insulin (HT, 8.3 +/- 1.2; C, 4.6 +/- 0.4 mU.L-1; P = .02), and C-peptide (HT, 1.7 +/- 0.2; C, 1.1 +/- 0.1 microgram.L-1; P = .006) concentrations were higher in hypertriglyceridemic subjects. The insulin and C-peptide responses to OGTT were greater in hypertriglyceridemic subjects (insulin, P = .005; C-peptide; P = .01). Hepatic glucose appearance in the postabsorptive state was similar (HT, 11.4 +/- 0.3; C, 10.9 +/- 0.7 mumol.kg-1.min-1; NS). At low insulin concentrations (HT, 20.7 +/- 1.4; C, 20.5 +/- 1.4 mU.L-1), hepatic glucose appearance was equally suppressed (HT, 9.6 +/- 0.9; C, 10.5 +/- 1.3 mumol.kg-1.min-1; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Psychomotor performance and counterregulatory responses during mild hypoglycemia in healthy volunteers.

The effect of mild hypoglycemia on psychomotor performance and counterregulatory responses was studied among 12 healthy volunteers. Each volunteer received two modified hyperinsulinemic glucose clamps. One morning, plasma glucose was held constant at euglycemic levels (4.9 mM) for 95 min, and another morning, it was lowered over 35 min and then held constant at hypoglycemic levels (3.4 mM) for 60 min. A battery of psychomotor tests and a questionnaire assessing hypoglycemic symptoms were administered before and repeated during the last 30 min of each clamp. The questionnaire and three selected psychomotor tests were also administered repetitively during the 1st h of each clamp. During the hypoglycemic studies, a rise was seen in plasma epinephrine and pancreatic polypeptide at 45 min. An increase in symptom scores was first recorded at 50 min during the hypoglycemic studies [median 4 (range 0-13) vs. 2 (5-6), P less than .05]. Performance was impaired on two psychomotor tests included in the battery. One was the trail making test on fine motor performance (-19.3 +/- 4.2 targets/min, mean +/- SE vs. 1.2 +/- 4.8 targets/min, P less than .05), and the other was the digit-symbol substitution (DSS) test on information processing and memory (18 +/- 3 vs. 29 +/- 4 symbols/min, P less than .03). Of the tests administered during the 1st h, performance was impaired on the DSS. This impairment became significant at 45 min (14 +/- 4 vs. 22 +/- 4 symbols/min, P less than .005). In conclusion, mild hypoglycemia selectively impairs psychomotor performance in healthy volunteers but not before the onset of glucose counterregulation and warning symptoms.