Metabolic response to experimental trauma: the time relation of post-traumatic protein metabolism

The relationship between time and the post-traumatic metabolic response was studied in a commonly used experimental model of trauma. Twenty nine rats underwent laparotomy and jugular vein sham catheterization as the standard trauma. The rats were fed ad libitum and compared to pair fed controls in terms of nitrogen balance and liver protein synthesis. The pairs of rats were divided into three groups according to the duration of the experiment, which was 24 h, 48 h or 72 h. The nitrogen balance was calculated daily and the liver protein synthesis in vitro measured in 10 rats after 48 h with an asanguinous perfusion system using L-(1-C(14))-Leucine. The metabolic effect of trauma was first detected in liver protein synthesis, which was diminished in the early post-traumatic period (percentage synthesis rates: post-traumatic 34.6 +/- 10.7 and pair fed 60.4 +/- 21.3, Mean +/- SD, P < 0.05). During this period the whole body nitrogen balances were similar (post-traumatic -1.200 +/- 1.440 and pair fed -0.880 +/- 1.130, gN/kg/48 h, mean +/- SD). On the third day, the response to nitrogen intake and the nitrogen balance became significantly worse in the post-traumatic rats (post-traumatic 0.214 +/- 1.680 and pair fed 1.236 +/- 1.220, gN/kg/day, mean +/- SD). These observations suggest that, firstly, the 'flow' phase has its onset on the third post-trauma day, and secondly that trauma does decrease liver protein synthesis, and this decrease lasts at least through the 'ebb' phase. The results indicate the necessity of defining the metabolic phase in experimental studies of post-traumatic metabolism.     

Effect of Different Respirator Adjustments on Central Haemodynamics in Open-Heart Surgery Patients

Changes in cardiac index (CI) mean pulmonary artery pressure (PAP), mean pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), and pulmonary artery vascular resistance (PVR), associated with spontaneous respiration (SR) and two different types of intermittent positive pressure ventilation (IPPPV and IPNPV) were studied in a total of 17 patients undergoing aortic valve replacement or myocardial revascularization. Swan-Ganz thermodilution pulmonary artery cardiac output catheters were used and the aim was to determine: whether postoperative cardiac output may paradoxically be greater during IPPPV than during IPNPV or SR; whether the use of "negative" pressure in the expiratory phase during controlled ventilation may be responsible for bringing about the central haemodynamic conditions prevailing during spontaneous respiration; and whether, in weaning from postoperative IPPPV to SR, there is a risk of pulmonary congestion as a consequence of possible autotransfusion. IPPPV connected with anaesthesia induction caused a highly significant deterioration central haemodynamics. The use of positive end-expiratory pressure (PEEP) is not to be recommended for such patients at this stage. On the first postoperative day, the mean CI was lower during IPPPV than during IPNPV (P less than 0.1) or during SR (P less than 0.05). The changes observed in CI, were, however, so slight that the authors consider the routine use of PEEP to be beneficial during controlled ventilation following major open-heart surgery. In some patients, the CI was paradoxically higher during IPPPV than during IPNPV or SR. The mean CI was nearly the same during IPNPV (3.32) as during SR (3.38). However, PAP, PCWP and PVR values were significantly higher during SR than during IPNPV. Thus, according to this study, the use of "negative" end-expiratory pressure during controlled ventilation did not in these patients produce central pressure conditions corresponding to spontaneous respiration. The present study supports the finding that in weaning from controlled ventilation with PEEP to SR there is a danger of pulmonary congestion. This could be predicted by measurement of pulmonary wedge pressure, but not by measurement of central venous pressure.     

Increased carotid atherosclerosis in andropausal middle-aged men

OBJECTIVES: This study examined the association between carotid artery intima-media thickness (IMT), serum sex hormone levels, and andropausal symptoms in middle-aged men. BACKGROUND: Male sex hormones may play a dual role in the pathogenesis of atherosclerosis in men by carrying both proatherogenic and atheroprotective effects. METHODS: We studied 239 40- to 70-year-old men (mean +/- SD: 57 +/- 8 years) who participated in the Turku Aging Male Study and underwent serum lipid and sex hormone measurements. Ninety-nine men (age 58 +/- 7 years) were considered andropausal (i.e., serum testosterone <9.8 nmol/l or luteinizing hormone [LH] >6.0 U/l and testosterone in the normal range), and in both situations, they had subjective symptoms of andropause (a high symptom score in questionnaire). Three were excluded because of diabetes. The rest of the men (age 57 +/- 8 years) served as controls. Carotid IMT was determined using high-resolution B-mode ultrasound, and serum testosterone, estradiol (E2), LH, and sex hormone-binding globulin were measured using standard immunoassays. RESULTS: Andropausal men had a higher maximal IMT compared with controls in the common carotid (1.08 +/- 0.34 vs. 1.00 +/- 0.23, p < 0.05) and in the carotid bulb (1.44 +/- 0.48 vs. 1.27 +/- 0.35, p = 0.003). Common carotid IMT correlated inversely with serum testosterone (p = 0.003) and directly with LH (p = 0.006) in multivariate models adjusted for age, total cholesterol, body mass index, blood pressure, and smoking. CONCLUSIONS: Middle-aged men with symptoms of andropause, together with absolute or compensated (as reflected by high normal to elevated LH) testosterone deficiency, show increased carotid IMT. These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men.     

Adrenocorticotropin and corticotropin-releasing hormone tests in preterm infants

The short ACTH test is used in evaluating the hypothalamo-pituitary-adrenal axis (HPA-axis) in preterm neonates after dexamethasone treatment. This test mainly examines primary adrenal suppression but is also used as a method to test secondary adrenal insufficiency because long-term deprivation of ACTH causes atrophy of the adrenal cortex. The CRH test, on the other hand, directly examines the function of the pituitary. We tested 18 infants in the neonatal intensive care unit with both the ACTH test and the CRH test to determine which of these two tests more reliably demonstrates HPA-axis suppression. One patient had normal responses both in the ACTH test and in the CRH test when the limit of 360 nmol/L was used as a sign of proper cortisol secretion. In four cases the patients' cortisol secretion would have been regarded as normal by the low-dose ACTH test, whereas the CRH test did not show an adequate cortisol response. In conclusion, the ACTH test did not reliably indicate HPA-axis suppression after a short (<2 weeks) course of dexamethasone therapy in this study. Therefore, whether the infant is or will be under acute stress after short glucocorticoid treatment, ensuring adequate cortisol secretion with the CRH test should be considered.     

Gender-specific change in leptin concentrations during long-term CPAP therapy

Purpose

Nasal continuous positive airway pressure (CPAP) alleviates sleepiness in patients with obstructive sleep apnoea syndrome (OSAS), but part of OSAS patients keep gaining weight. Leptin and insulin-like growth factor-1 (IGF-1) interact with energy balance, and CPAP therapy has been suggested to influence these endocrine factors. We hypothesised that leptin would decrease during long-term CPAP therapy, and weight gain would associate with OSAS severity, lower CPAP adherence, lower IGF-1, and leptin concentrations.

Methods

Consecutive patients (n?=?223) referred to sleep study with suspected OSAS were enrolled. Patients underwent cardiorespiratory polygraphy at baseline. Questionnaires were completed, and blood samples were drawn both at baseline and after 3 years. A total of 149 (67%; M 65, F 84) patients completed the follow-up. Plasma samples were available from 114 patients, 109 of which with CPAP adherence data (49 CPAP users, 60 non-users).

Results

At baseline, the CPAP users were more obese and had more severe OSAS than the non-users. Leptin concentrations did not differ. After follow-up, leptin concentrations were higher in CPAP users (30.2 ng/ml vs. 16.8 ng/ml; p?=?0.001). In regression analysis, increase in leptin concentrations was independent of age, baseline body mass index (BMI), or the change in BMI. Leptin concentrations increased among females (??8.9 vs. 12.7 ng/ml; p?<?0.001); whereas in men, CPAP did not have an effect, if not opposed the natural decrease in leptin observed in men not using CPAP. Change in IGF-1 levels did not differ.

Conclusions

Our results suggest increase in leptin concentrations during long-term CPAP therapy among females.

     

Clinical features and circulating gonadotropin, insulin, and androgen interactions in women with polycystic ovarian disease

OBJECTIVE: To investigate the interactions of hyperinsulinemia and inappropriate gonadotropin secretion in women with polycystic ovarian disease (PCOD). DESIGN: Comparative study of endocrinologic parameters in subjects with PCOD. SETTING: Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. PATIENTS: Fourteen nonobese and 10 obese patients with PCOD. Seven healthy women for reference data collection. Normal thyroid function, serum prolactin concentration, normal diurnal cortisol variation, euglycemia in all subjects. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, immunoreactive luteinizing hormone (LH), bioactive LH, and follicle-stimulating hormone (FSH). RESULTS: The concentration of insulin was higher and that of bioactive LH was lower in obese than in nonobese PCOD women in whom the levels were also above the upper reference value. There was a negative correlation between insulin and bioactive LH levels (r = -0.57). Bioactive LH correlated inversely with the body mass index (BMI) (r = -0.50). After eliminating the effect of the BMI, the correlation between bioactive LH and insulin was no longer significant (r = -0.37). The bioactive LH and immunoreactive LH/FSH ratio correlated significantly (r = 0.68). CONCLUSIONS: These data demonstrate that hyperandrogenic women can be divided into two subgroups: those with insulin resistance, normal or minimally elevated LH, and markedly elevated insulin levels; and those with elevated LH levels, no insulin resistance, and normal insulin concentrations. Obesity is associated with the former, and high bioactive LH levels with the latter subgroup.     

The effect of conventional vitamin D(2) supplementation on serum 25(OH)D concentration is weak among peripubertal Finnish girls: a 3-y prospective study

OBJECTIVES: To study the effect of vitamin D supplementation and the impact of summer season on serum 25-hydroxyvitamin D (S-25(OH)D) in Finnish 9-15-y-old girls. DESIGN: Three-year follow-up study with vitamin D(2) supplementation using D(2) 10 microg daily from October to January for the first and from October to February for the second winter as well as 20 microg daily from October to March for the third winter. SETTING: Paavo Nurmi Centre, University of Turku, Turku, Finland. SUBJECTS: A total of 171 female volunteers aged 9-15 y. METHODS: Vitamin D and calcium intakes were estimated by a semi-quantitative food frequency questionnaire (FFQ). S-25(OH)D was measured by radioimmunoassay. RESULTS: The median daily dietary intakes of vitamin D and calcium were 3.8 microg (interquartile range (IQR) 2.7-5.0) and 1451 mg (IQR 1196-1812), respectively, over 3 y. The prevalence of severe hypovitaminosis D (S-25(OH)D<20 nmol/l) was 14% and of moderate hypovitaminosis D (20 nmol/l < or = S-25(OH)D < or = 37.5 nmol/l) 75% at baseline in winter. None of the participants had severe hypovitaminosis D in summer. The effect of 10 microg of D(2) daily was insufficient to raise S-25(OH)D from baseline. The daily supplementation of 20 microg of D(2) increased S-25(OH)D significantly in wintertime compared with the non-supplement users (to 45.5 vs 31.8 nmol/l; P<0.001). None of the subjects with vitamin D(2) supplementation approximately 20 microg daily had severe hypovitaminosis D; however, 38% of those participants had moderate hypovitaminosis D at 36 months. Sun exposure in summer raised mean S-25(OH)D to 62.0 nmol/l. Both the daily supplementation of approximately 20 microg of D(2) and summer sunlight exposure had more effect on those who had severe hypovitaminosis than those who had a normal vitamin D status (increase of 24.2 vs 0.9 nmol/l (P<0.001), and 38.8 vs 18.2 nmol/l (P<0.001), respectively). CONCLUSION: Vitamin D supplementation daily with 20 microg is needed to prevent hypovitaminosis D in peripubertal Finnish girls in winter. Sunlight exposure in summer is more effective than approximately 20 microg of D(2) supplementation daily in winter to raise S-25(OH)D. Both the daily supplementation with 20 microg of D(2) and summertime sunlight exposure had more effect on those who had severe hypovitaminosis D than those who had a normal vitamin D status. SPONSORSHIP: Supported by the Yrj? Jahnsson Foundation and the Medical Research Foundation of the Turku University Central Hospital.     

Luteal function declines after laparoscopic sterilization by Hulka or Filshie clips

We evaluated the influence of laparoscopic sterilization by Hulka or Fishie clips on corpus luteum function. Changes in corpus luteum function were evaluated in 46 women, before and after sterilization by Hulka (n = 22) or Filshie clips (n = 24). The mean age of the participants was 37 years (range 31-43 years). All women were healthy with regular menstrual cycles. Serum progesterone (P) was measured in one cycle before, and 3 and 12 months after the sterilization on cycle day 20-24. Endometrial biopsies were performed in the luteal phase before and one year after the procedure. The women measured the basal body temperature daily and kept a menstrual diary. The luteal phase P concentrations declined after the sterilization and the values were at the lowest level 3 months after the procedure (27.9 +/- 14.3 nmol/L vs. 18.7 +/- 13.4 nmol/L, = 0.0016). The values seemed to have recovered by 12 months (23.0 +/- 14.0 nmol/L, = 0.114 vs. baseline). Endometrium tended to be out-of-phase more frequently 1 year after the sterilization than before the surgery (= 0.065). Laparoscopic tubal sterilization is associated with an increased risk of luteal phase deficiency. However, the change may be only temporary in nature.     

Obesity regulates bioavailable testosterone levels in women with or without polycystic ovary syndrome

OBJECTIVE: To evaluate [1] the effects of levels of sex hormone-binding globulin (SHBG), albumin, and total testosterone on the distribution of testosterone between SHBG-bound and non-SHBG-bound fractions; [2] the independent effects of polycystic ovary syndrome (PCOS) and body mass index on serum levels of total testosterone, non-SHBG-bound testosterone, SHBG, and albumin; and [3] the usefulness of levels of total testosterone and non-SHBG-bound testosterone and of the free androgen index in the diagnosis of PCOS. DESIGN: Retrospective clinical study. SETTING: An academic research environment. PATIENT(S): Forty-three women with oligomenorrhea and PCOS. Twenty-five women with regular menstrual cycles and without hirsutism served as controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Levels of non-SHBG-bound testosterone, total testosterone, SHBG, and albumin in serum. RESULT(S): Levels of total testosterone and non-SHBG-bound testosterone, and the free androgen index were higher in patients with PCOS than in healthy controls. PCOS did not have an effect on the levels of SHBG or albumin, or on the percentage of non-SHBG-bound testosterone. Levels of SHBG and albumin were inversely related to body mass index. The percentage and concentration of non-SHBG-bound testosterone and the free androgen index were directly related to body mass index. Hirsutism did not have an effect on any outcome measure. CONCLUSION(S): The distribution of total testosterone into SHBG-bound and non-SHBG-bound fractions is associated with body mass index, not with PCOS. The high levels of non-SHBG-bound testosterone and the high free androgen index in patients with PCOS reflect mainly high levels of total testosterone. Thus, the measurement of levels of non-SHBG-bound testosterone and the calculation of the free androgen index provide no further information in the diagnosis of PCOS beyond that provided by the measurement of levels of total testosterone.