Surgery for ruptured abdominal aortic aneurysm and early mortality in women. Risk factors and complication profile.

AIM: Repair of ruptured abdominal aortic aneurysm (rAAA) is reported to have a higher mortality in women than in men. The aim was to study whether this difference could be verified in our institution and secondary if difference in risk- and complication profiles could explain the higher 30 day mortality after surgery for rAAA in women. METHODS: During the period 1983-2009 1649 patients, 1348 men and 301 women, were operated consecutively for infrarenal abdominal aortic aneurysm (AAA); 430 patients had rAAA, 98 women and 332 men. Co-morbidities were identified from the patients' medical records. Outcome measures within 30 days were mortality, cardiac disease (heart attack, heart failure), cerebrovascular disease (stroke, TIA), renal insufficiency (serum creatinine >140 µmol/L), major amputation, bowel infarction, pancreatitis and graft related complications. RESULTS: Compared to men, women had higher 30 d mortality after surgery for rAAA (54.1% vs. 36.3%, P=0.002). Women were significantly older than men (76 years vs. 73 years, P=0.001). In the period 1995-2009 women had more autoimmune diseases than men (P=0.045). There was no significant difference between men and women for the other measured outcomes. CONCLUSION: During the period 1995-2009, autoimmune disease were more common among women than men. For all other parameters recorded, there were no differences in risk - or complication profile that could explain the higher 30 d mortality in female patients after surgery for rAAA.

Biochemical characterization of four novel mutations in the thyroid hormone receptor beta gene in patients with resistance to thyroid hormone.

In resistance to thyroid hormone (RTH), decreased tissue responsiveness to thyroid hormones is usually caused by mutations in the thyroid hormone receptor beta (THRB) gene. Subsequently, in serum the level of thyroid stimulating hormone (TSH) is not suppressed despite increased concentrations of thyroxine (T4) and triiodothyronine (T3). In our laboratory, DNA sequences of exon 7 to 10 in the THRB gene have been analysed in individuals with biochemical signs of RTH. Four novel point mutations were identified (I250T, A279E, T327A and L440P) and their effects on T3 binding activity characterized. The mutations were introduced into a vector carrying the wild-type THRB cDNA by in vitro mutagenesis. T3-binding activity was measured by a filter-binding assay procedure in receptors generated from the vector by in vitro transcription and translation. Specific binding was calculated as total activity subtracted by non-specific activity. The association constants (Ka) of the wildtype (WT) and mutant receptors were determined by Scatchard analysis. No specific T3-binding was observed for the receptor with the A279E mutation. The binding affinity was reduced by 74% in the T327A mutant and by about 50% in the I250T and L440P mutants compared to the WT receptor (Ka = 4.2 x 10(10) L/mol). The reduction of T3-binding affinity caused by the four mutations in our study is comparable to the effects of THRB gene mutations found in other patients with RTH and supports the assumption that the signs of RTH observed in our patients are caused by the mutations.

Cross-sex pattern of bone mineral density in early onset gender identity disorder.

Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment at months 3 and 12. The study included 33 EO-GID patients who were approved for sex reassignment and a control group of 122 healthy Norwegians (males, n=77; females, n=45). Male patients (n=12) received an oral dose of 50 mug ethinylestradiol daily for the first 3 months and 100 mug daily thereafter. Female patients (n=21) received 250 mg testosterone enantate intramuscularly every third week. BMD, TBF and TLBM were estimated using dual energy X-ray absorptiometry (DXA). In male patients, the DXA measurements except TBF were significantly lower compared to their same-sex control group at baseline and did not change during treatment. In female patients, the DXA measurements were slightly higher than in same-sex controls at baseline and also remained unchanged during treatment. In conclusion, this study reports that body composition and bone density of EO-GID patients show less pronounced sex differences compared to controls and that bone density was unaffected by cross-sex hormone treatment.

Insulin sensitivity in subjects with secondary hyperparathyroidism and the effect of a low serum 25-hydroxyvitamin D level on insulin sensitivity.

To investigate the relation between secondary hyperparathyroidism (SHPT) and insulin sensitivity, 15 subjects with SHPT (serum PTH >6.4 pmol/l, serum calcium <2.40 mmol/l, and normal serum creatinine) and 15 control subjects were investigated with an oral glucose tolerance test (OGTT) and a 3-h hyperglycemic clamp. Body composition was measured with dual-energy X-ray absorptiometry. No differences were found between the SHPT and control groups on any indices of glucose or insulin metabolism. However, when dividing the 30 subjects in the upper and lower halves according to serum 25-hydroxyvitamin D levels (<59 and >58 nmol/l), those in the lower half had significantly higher 2-h serum insulin value at the OGTT, significantly higher insulin secretion during the last hour of the clamp, and significantly lower insulin sensitivity index (ISI; glucose infusion rate/insulin secretion during the last hour of the clamp). In a multiple linear regression analysis correcting for age, gender, and body mass index (BMI), the serum 25-hydroxyvitamin D level was significantly and positively associated with the ISI. The amounts of total body and truncal fat were negatively and significantly associated with the ISI, whereas no association between measures of lean body mass were associated with insulin secretion or sensitivity.

Does rapid intraoperative parathyroid hormone analysis predict cure in patients undergoing surgery for primary hyperparathyroidism? A prospective study.

BACKGROUND AND AIMS: Preoperative 99mTc-sestamibi scintigraphy is used by many surgeons to identify the anatomical location of pathological parathyroid glands in patients undergoing surgical treatment for hyperparathyroidism. However, false negative results do occur. It has been suggested that intraoperative parathyroid hormone (PTH) analysis may enhance the possibility of performing successful focused, unilateral neck surgery in these patients. This study aimed to evaluate whether an adequate fall in intraoperative parathyroid hormone values predicts the removal of all hyperfunctioning parathyroid tissue and postoperative normocalcemia. MATERIAL AND METHODS: One hundred consecutive patients undergoing surgery for hyperparathyroidism had preoperative 99mTc-sestamibi scintigraphy and intraoperative parathyroid hormone (PTH) analysis. A fall in intraoperative PTH value by more than 50% of baseline value ended the procedure. This prospective study presents the clinical and biochemical results. RESULTS: The overall sensitivity of the 99mTc-sestamib scintigraphy was 88% and for single adenomas 95%. The scintigraphy failed to detect the correct pathology in all cases with multiglandular disease (7 patients). A fall in intraoperative PTH value by more than 50% of baseline value was achieved in all patients. The combination of intraoperative PTH analysis and 99mTc-sestamibi scintigraphy enabled us to limit the operation to a focused, unilateral operation in 87 of the 100 patients. All patients were normocalcemic postoperatively. CONCLUSIONS: A fall in intraoperative PTH value more than 50 % of baseline value seems to predict postoperative normocalcemia and the removal of all hyperfunctioning parathyroid tissue. Bilateral neck exploration is avoided in the majority of patients.

Elective open operation for abdominal aortic aneurysm in octogenarians--survival analysis of 105 patients.

OBJECTIVES: To study early mortality and long-term survival of patients more than 80 years of age having elective open repair for abdominal aortic aneurysm (AAA). DESIGN: Retrospective multicenter cohort study. MATERIAL: One hundred and five patients, 23 women and 82 men, with a median age of 82 years, operated at three Norwegian hospitals during the period 1983-2002. METHOD: Survival analyses were based on data from medical records and the Norwegian Registrar's Office of Births and Deaths. Expected survival was based on mortality rates of the general population, matched by age, sex, and calendar period. Relative survival was calculated as the ratio between the observed and the expected survival. RESULTS: During the study period there has been a 10 fold increase in octogenarians treated with open operation for AAA. Early mortality (30-day) for the whole group of patients was 10.5% (95% confidence interval (95% CI) 5.3-18.0), and similar for both genders. The 5-year survival rate was 47% (95% CI 35.9-57.4), and not significantly different from that of a matched group in the general population. Patients aged 84 years or more had a median survival time of 35 months (95% CI 18.5-51.6). CONCLUSION: The number of AAA operations in octogenarians has increased considerably during 20 years. Octogenarians operated electively for AAA has higher 30-day mortality as compared to younger patients. Their long-term survival appears similar to a matched control group. The benefit of surgery must be carefully considered against the perioperative risk, especially for the oldest octogenarians.

Quality of data reported on abdominal aortic aneurysm repair--a comparison between a national vascular and a national administrative registry.

OBJECTIVE: To study consistency of data and completeness of reporting in a national vascular registry, NorKar, and a national administrative registry, The Norwegian patient register (NPR). DESIGN: Comparative registry-based national study supplemented with a comprehensive control of patients registered in one major hospital. MATERIAL: All patients registered with a procedure-code for treatment of AAA in NorKar or NPR during 2001 or 2002, were included. METHOD: We compared the reporting of procedure-codes, diagnosis-codes and in-hospital deaths after treatment for abdominal aortic aneurysm (AAA) in the two registries to evaluate completeness. Consistency between procedure-codes and diagnoses were evaluated within both registries. Completeness of reporting to one NorKar Local Registry was investigated in more detail in one of the hospitals. RESULTS: Compared with the NPR numbers, NorKar contained 69% of the patients treated for AAA in Norway, while completeness for NorKar member hospitals was 84%. The detailed investigation in one of the hospitals showed a completeness of 91% and a false inclusion of 5.3% of all cases treated for AAA. The consistency between procedure-codes and diagnosis-codes was 93% in both registries. We found evidence of substantial underreporting of in-hospital deaths to NorKar in several hospitals. Overall reporting of early deaths to NorKar relative to completeness of reported cases was estimated to 72%. CONCLUSION: There is an underreporting of patients with AAA to NorKar according to the NPR numbers and a need for better control of procedure-diagnosis consistency in both registries. There seems to be a substantial underreporting of early deaths to NorKar. Introduction of unique patient-identifiable data could improve the quality of both registries by making matching of data possible.

Effects of acute hypercalcaemia on blood pressure in subjects with and without parathyroid hormone secretion.

AIM: Acute hypercalcaemia increases the blood pressure, but the mechanism is uncertain. It may partly be the result of the concomitant fall in parathyroid hormone (PTH) secretion as PTH has been reported to have a vasodilator effect. To elucidate this, we infused calcium intravenously in subjects with and without PTH secretion. METHODS: Seven thyroparathyroidectomized subjects with undetectable PTH levels and 10 controls were studied twice, once with a calcium clamp technique that increased plasma ionized calcium in two steps of 0.1 mmol L(-1), each step lasting 60 min, and once with a placebo infusion. RESULTS: On the placebo day, blood pressure and all other variables were unaffected in both groups. On the calcium day, systolic blood pressure increased gradually and significantly from end of baseline till end of the calcium infusion in the controls (123.5 +/- 19.8 and 134.2 +/- 17.6 mmHg, P < 0.004) but not in the thyroparathyroidectomized subjects (124.9 +/- 15.7 and 126.0 +/- 20.6 mmHg, P = ns). Serum PTH levels fell promptly in the controls, and in both groups there was a significant increase in serum phosphate. The diastolic blood pressure and pulse rate, and the plasma adrenaline and noradrenaline, plasma renin activity, and serum aldosterone levels were unaffected by the calcium infusion. CONCLUSION: During acute hypercalcaemia the blood pressure increase appears unrelated to catecholamine secretion and the renin-aldosterone system, whereas the fall in PTH secretion may play a contributory role.

Serum parathyroid hormone (PTH) levels in smokers and non-smokers. The fifth Tromsø study.

OBJECTIVE: Smoking is associated with reduced bone density and calcium absorption, and reduced serum levels of vitamin D. A compensatory increase in serum parathyroid hormone (PTH) would therefore be expected as a result of an altered calcium balance. However, reports on PTH levels in smokers are conflicting. As serum PTH levels give important information on the calcium balance, the PTH levels in smokers are of interest. SUBJECTS AND METHODS: In the fifth Tromsø study, smoking status was recorded and serum PTH measured in 7896 subjects. Intakes of calcium and vitamin D were evaluated with a food-frequency questionnaire. In a follow-up study on 205 subjects, serum 25-hydroxyvitamin D, calcium absorption, and renal excretion of calcium were measured in addition. RESULTS: The serum PTH levels were significantly lower in smokers than non-smokers (3.1+/-1.4 vs 3.6+/-1.9 pmol/l in males; 3.1+/-1.5 vs 3.6+/-1.8 pmol/l in females (P < 0.001) after correcting for confounding variables, linear regression). In the smokers, there was no association between number of cigarettes smoked and serum PTH. One year after quitting smoking, serum PTH levels were similar to those of people who had never smoked. The smokers had significantly lower intake of vitamin D, lower serum levels of 25-hydroxyvitamin D and lower calcium absorption. The intake of calcium and the renal excretion of calcium were similar to that in non-smokers. CONCLUSIONS: Smokers have lower serum PTH levels than non-smokers. This cannot be explained by the predictors of serum PTH measured in our study.

Coeliac disease in subjects with secondary hyperparathyroidism.

OBJECTIVE: Coeliac disease (CD) may present in its classical form with diarrhoea and weight loss, but also with atypical symptoms that are both related and unrelated to malabsorption. Osteomalacia or osteopenia following malabsorption of calcium and vitamin D is known to occur in patients with CD, and in such cases secondary hyperparathyroidism (SHP) caused by low serum calcium levels is frequently found. However, the prevalence of CD in subjects with SHP has not been reported. MATERIAL AND METHODS: In the Tromsø study 2001, serum parathyroid hormone (PTH) and calcium were measured in 7954 subjects of whom 6061 were eligible for follow-up. From this group, 97 subjects with SHP (serum PTH> or =6.5 pmol/l and serum calcium <2.40 mmol/l) and 104 matched control subjects were re-examined with serological tests for CD (anti-tissue transglutaminase, anti-gluten IgA and IgG). RESULTS: CD was diagnosed in 4 subjects, all from the original SHP group. At the re-examination, only 29 of the 97 subjects with SHP still had elevated serum PTH levels. Among these were 3 of the subjects with CD. When grouping the serological test results as negative, borderline or positive, there was a significant difference between the SHP group and the controls for anti-tissue transglutaminase and anti-gluten IgA (p<0.05). CONCLUSIONS: Subjects with SHP, at least when SHP is persistent, should be tested for CD.

Prevalence and predictors of vitamin D deficiency in five immigrant groups living in Oslo, Norway: the Oslo Immigrant Health Study.

OBJECTIVE: To study the prevalence of vitamin D deficiency and to identify possible predictors of vitamin D deficiency in five main immigrant groups in Oslo. DESIGN: Cross-sectional, population-based. SETTING: City of Oslo. SUBJECTS: In total, 491 men and 509 women with native countries Turkey, Sri Lanka, Iran, Pakistan and Vietnam living in the county of Oslo. RESULTS: Median serum 25(OH)D level (s-25(OH)D) was 28 nmol/l, ranging from 21 nmol/l in women born in Pakistan to 40 nmol/l in men born in Vietnam. Overall prevalence of vitamin D deficiency defined as s-25(OH)D<25 nmol/l was 37.2%, ranging from 8.5% in men born in Vietnam to 64.9% in women born in Pakistan. s-25(OH)D did not vary significantly with age. s-25(OH)D was higher in blood samples drawn in June compared to samples obtained in April, but not significantly for women. Reported use of fatty fish and cod liver oil supplements showed a strong positive association with s-25(OH)D in all groups. Education length was positively associated with s-25(OH)D in women, whereas body mass index (BMI) was inversely associated with s-25(OH)D in women. These two variables were not related to vitamin D deficiency in men. CONCLUSIONS: There is widespread vitamin D deficiency in both men and women born in Turkey, Sri Lanka, Iran, Pakistan and Vietnam residing in Oslo. The prevalence of vitamin D deficiency is higher in women than in men, and it is higher in those born in Pakistan and lower in those born in Vietnam compared to the other ethnic groups. Fatty fish intake and cod liver oil supplements are important determinant factors of vitamin D status in the groups studied. BMI and education length are also important predictors in women.

Emergency non-ruptured abdominal aortic aneurysm.

OBJECTIVES: To investigate symptoms and early mortality (<30 days) following open surgery for emergency, symptomatic non-ruptured abdominal aortic aneurysm (AAA). DESIGN: Retrospective cohort study. PATIENTS AND METHODS: During the period 1983-1994, 129 patients had an emergency admission, followed by surgery, for symptomatic non-ruptured AAA. Sixty-one received surgery within 24 h of admission and 68 received surgery more than 24 h after admission (median 135 h, inter-quartile range: 51-239 h). During the same period 239 patients had elective surgery for non-ruptured AAA. Early mortality (<30 days), symptoms and co-morbidities were recorded. Data were retrieved from the patient records. RESULTS: Mortality (30 days) was 18% in the 61 patients having surgery within 24 h of emergency admission for non-ruptured AAA. Mortality following either delayed surgery (semi-elective) after emergency admission or elective surgery was 4.2% (p=0.0002). Four out of 11 patients who died within 30 days following an acute operation had previously been declared unfit for elective surgery. One additional emergency patient had been found unfit for open surgery, but survived a delayed operation. CONCLUSION: The high mortality rate of patients with non-ruptured, symptomatic AAA undergoing surgery within 24 h of admission appears to be influenced by several factors, including co-morbidities and the acute operation. We propose that the 30-day mortality for non-ruptured AAA should be reported in two categories: mortality rate for elective surgery and mortality for surgery performed within 24 h of emergency admission. The term 'emergency non-ruptured' is a suitable term for the latter group.

Vitamin D deficiency, bone mineral density and weight in patients with advanced pulmonary disease.

OBJECTIVE: To study the influence of underweight, body composition and vitamin D deficiency on bone mineral density in patients with advanced pulmonary disease. DESIGN: Cross-sectional study with time span for inclusion set at 5 years. SETTING: The clinical work and biochemical analyses were carried out at Rikshospitalet University Hospital, Norway. Analyses for vitamin D metabolites and bone markers were carried out at Aker University Hospital, and bone measurements at Clinic of Osteoporosis. SUBJECTS: Seventy-one candidates for lung transplantation (63% chronic obstructive pulmonary disease, 42 underweight and 29 normal weight) were included. MAIN OUTCOME MEASURES: Body composition, bone mineral density at lumbar spine and femur neck, serum concentration of calcidiol and vitamin D intake. RESULTS: Subnormal calcidiol levels were present in 52% of the underweight patients and 69% of the normal-weight patients. The resulting models of linear regression showed that for the lumbar spine T scores model, the total variation of 16.7% was explained by group (underweight/normal weight), sex and age. For the femur neck T scores model, the total variation of 20.4% was explained by the interaction of underweight and vitamin D deficiency (with borderline significance) and by arm muscle circumference percentage of standard. In patients with normal calcidiol levels, the median intake of vitamin D was 17 microg in the underweight patients and 11 microg in the normal-weight patients. CONCLUSIONS: Vitamin D deficiency was common in both underweight and normal-weight patients, but only in the underweight patients, an association between vitamin D deficiency and reduced femur neck T scores was indicated.

Inflammatory aortic aneurysm is associated with increased incidence of autoimmune disease.

OBJECTIVE: It has been suggested that certain genetic risk factors indicative of an autoimmune mechanism can be identified in patients with inflammatory aortic aneurysm (IAA). We therefore investigated whether there was a higher incidence of autoimmune diseases in patients with IAA. Further, we explored risk factors, need for in-hospital resources, and early results of treatment, in a case-control study in a university hospital setting. Material and methods From 1983 to 1994, 520 patients were operated because of abdominal aortic aneurysm (AAA). Thirty-one patients had IAA. Control subjects were matched for aneurysm rupture, emergency or elective hospital admission, and date of operation. Two noninflammatory AAA were included for every IAA. RESULTS: Of the 31 patients with IAA, 6 patients (19%) had autoimmune disease, compared with none of the control subjects (P =.0017). Two patients had rheumatoid arthritis, 2 patients had systemic lupus erythematosus, 1 had giant cell arteritis, and 1 patient had an undifferentiated seronegative polyarthritis diagnosed as rheumatoid arthritis. Nineteen patients (61%) with IAA had involvement of the duodenum, and 8 patients (26%) had hydronephrosis with ureteral involvement. Operating time was longer in the IAA group, which also had a higher need for blood transfusion. Hospital stay, intensive care unit stay, and 30-day mortality were similar in the two groups. CONCLUSION: Except for longer operating time and more need for blood transfusions in the IAA group, use of hospital resources was similar after operations to treat IAA or noninflammatory AAA. The study findings indicate an association between IAA and autoimmune disease. This is in accordance with other reports that showed a genetic risk determinant mapped to the human leukocyte antigen (HLA) molecule in these patients. Further research is necessary to explore whether IAA might be a separate entity with a role of antigen binding in the origin of the disease.

Thyroid dysfunction during treatment of chronic hepatitis C with interferon alpha: no association with either interferon dosage or efficacy of therapy.

OBJECTIVES: Treatment of chronic hepatitis C with interferon-alpha (IFN-alpha) may induce thyroid disorders. We evaluated whether this risk is related to the dosage of IFN-alpha or the virological treatment response. Other possible risk factors as well as the evolution of the thyroid abnormalities were also studied. METHODS: In this prospective trial (n=254), thyroid-stimulating hormone (TSH), free thyroxin (fT4) and thyroid peroxidase autoantibodies were measured before, during and after treatment for hepatitis C virus (HCV). The patients were randomized to either induction therapy [IFN-alpha 6 million units (MIU) daily for 4 weeks and 3 MIU 3/7 days for 22 weeks] or conventional therapy [IFN-alpha 3 MIU 3/7 days for 26 weeks]. In addition, all patients received ribavirin (1000 or 1200 mg) daily. Sustained virological response was defined as loss of detectable HCV RNA at 6 months follow-up. Thyroid dysfunction was defined as TSH level below or above the normal range (0.2-4.5 MIU L-1). RESULTS: Biochemical thyroid dysfunction developed in 30 (11.8%) of 254 patients. Hypothyroidism (TSH > 4.5 MIU L-1) was seen in 20 and hyperthyroidism (TSH < 0.2 MIU L-1) in 10 patients. Nine of the 30 patients developed symptomatic thyroid disease and HCV treatment was discontinued because of thyroid dysfunction in three of these patients. Thyroid dysfunction occurred in 15 (11.7%) of 128 patients who received high-dose IFN-alpha induction therapy as compared with 15 (11.9%) of 126 patients who received conventional IFN-alpha therapy (P=0.96). Amongst 231 patients who completed all 6 months of HCV treatment, a sustained virological response was obtained in 19 (66%) of 29 with thyroid dysfunction and 109 (54%) of 202 without (P=0.24). By multivariate analysis female gender and Asian origin were independent predictors of developing biochemical thyroid dysfunction (P < 0.01). CONCLUSION: Thyroid dysfunction occurred in 11.8% of patients treated for chronic hepatitis C with IFN-alpha and ribavirin. Neither the IFN-alpha dosage nor the virological response to treatment were related to the incidence of thyroid dysfunction.

Simulation of a knee joint replacement during a gait cycle using explicit finite element analysis.

The stress distribution within the polyethylene insert of a total knee joint replacement is dependent on the kinematics, which in turn are dependent on the design of the articulating surfaces, the relative position of the components and the tension of the surrounding soft tissues. Implicit finite element analysis techniques have been used previously to examine the polyethylene stresses. However, these have essentially been static analyses and hence ignored the influence of the kinematics. The aim of this work was to use an explicit finite element approach to simulate both the kinematics and the internal stresses within a single analysis. A simulation of a total knee joint replacement subjected to a single gait cycle within a knee wear simulator was performed and the results were compared with experimental data.The predicted kinematics were in close agreement with the experimental data. Various solution-dependent parameters were found to have little influence on the predicted kinematics. The predicted stresses were found to be dependent on the mesh density. This study has shown that an explicit finite element approach is capable of predicting the kinematics and the stresses within a single analysis at relatively low computational cost.

Are patients with Hirschsprung's disease prediabetic?

Hirschsprung's disease (HD) is considered a focal disease usually confined to the distal colon and rectum. However, autonomic dysfunction and dysmotility in the upper gastrointestinal tract have been reported, suggesting that this disease is not only confined to the distal gastrointestinal tract. This study examines the fasting and postprandial levels of glucose and insulin in adult patients with HD to elucidate whether there might also be an endocrine involvement in this disease. Sixteen patients with surgically treated HD during early childhood and 17 healthy subjects were studied. All subjects ingested a caloric liquid meal containing glucose, lactose, maize oil, and water (2,020 kJ) after an overnight fast. Blood samples were collected at regular intervals for insulin and glucose analyses. Fasting levels of both glucose (P <.05) and insulin (P <.02) were significantly higher in patients compared with healthy controls. Peak concentration of insulin following meal intake was significantly higher in the patient group (P <.05), and peak concentration of glucose tended to be higher in patients compared with controls (P =.06). There was no correlation between body mass index and serum levels of glucose or insulin. The present study shows that adult patients treated for HD during childhood have an impaired glucose and insulin homeostasis, indicating a mild degree of insulin resistance. This may imply susceptibility towards development of non-insulin-dependent diabetes mellitus.

Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective.

Three to 12 h of mild hypothermia (HT) starting after hypoxia-ischemia is neuroprotective in piglets that are anesthetized during HT. Newborn infants suffering from neonatal encephalopathy often ventilate spontaneously and are not necessarily sedated. We aimed to test whether mild posthypoxic HT lasting 24 h was neuroprotective if the animals were not sedated. Thirty-nine piglets (median weight 1.6 kg, range 0.8-2.2 kg; median age 24 h, range 7-48 h) were anesthetized and ventilated and subjected to a 45-min hypoxic (FiO(2) approximately 6%) global insult (n = 36) or sham hypoxia (n = 3). On reoxygenation, 18 were maintained normothermic (NT, 39.0 degrees C) for 72 h, and 21 were cooled from 39 (NT) to 35 degrees C (HT) for the first 24 h before NT was resumed (18 experimental, three sham hypoxia). Cardiovascular parameters and intermittent EEG were documented throughout. The brain was perfusion fixed for neuropathology and five main areas examined using light microscopy. The insult severity (duration in minutes of EEG amplitude < 7 microV) was similar in the NT and HT groups, mean +/- SD (28 +/- 7.2 versus 27 +/- 8.6 min), as was the mean FiO(2) (5.9 +/- 0.7 versus 5.8 +/- 0.8%) during the insult. Six NT and seven HT piglets developed posthypoxic seizures that lasted 29 and 30% of the time, respectively. The distribution and degree of injury (0.0-4.0, normal-maximal damage) within the brain (hippocampus, cortex/white matter, cerebellum, basal ganglia, thalamus) were similar in the NT and HT groups (overall score, mean +/- SD, 2.3 +/- 1.5 versus 2.4 +/- 1.3) as was the EEG background amplitude at 3 h (13 +/- 3.5 versus 10 +/- 3.3 microV). The HT animals shivered and were more active. The sham control group (n = 3) shivered but had normal physiology and neuropathology. Plasma cortisol was significantly higher in the HT group during the HT period, 766 +/- 277 versus 244 +/- 144 microM at 24 h. Mild postinsult HT for 24 h was not neuroprotective in unsedated piglets and did not reduce the number of animals that developed posthypoxic seizures. Cortisol reached 3 times the NT value at the end of HT. We speculate that the stress of shivering and feeling cold interfered with the previously shown neuroprotective effect of HT. Research on the appropriateness of sedation during clinical HT is urgent.

Increased neuroendocrine response to a repeated bout of endurance exercise.

This study was designed to compare a first bout of high-intensity endurance exercise with a second bout of similar exercise on the same day, and thereby test the hypothesis that the endocrine response elicited by a second bout is more pronounced compared with a single bout of exercise. Nine male, elite endurance athletes participated in three trials of 24-h duration: 1) complete bed rest (REST), 2) one bout of exercise (ONE), and 3) two bouts of exercise separated by a 3-h rest period (TWO). Each exercise bout consisted of a 10-min warm-up at 50% of VO(2max) followed by 65 min at 75% of VO(2max) on a cycle ergometer. Exercise was performed between 11:00 a.m. and 12:15 a.m. (only in TWO) and 3:15 and 4:30 p.m. (both ONE and TWO). The subjects rested in bed at all hours except when exercising. Blood was sampled 11 times at identical time-points until 7:30 a.m. the next morning. We observed significantly increased levels of epinephrine, norepinephrine, ACTH, cortisol, and growth hormone, and decreased levels of testosterone during and/or after the second bout of exercise compared with the first bout. No difference was observed for insulin, follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, free fraction of thyroxin or insulin-like growth factor 1. Thus, this study demonstrates a more pronounced neuroendocrine response to a second bout of exercise on the same day compared with a first/single bout, involving both the sympatho-adrenal system and the hypothalamo-pituitary-adrenal axes.