Estimating Energy Expenditure using Individualized, Power-Specific Gross Efficiencies.

Our purpose was to determine if using an individual's power-specific gross efficiency improves the accuracy of estimating energy expenditure from cycling power. 30 subjects performed a graded cycling test to develop 4 gross efficiencies: individual power-specific gross efficiencies, a group mean power-specific gross efficiency, individual fixed gross efficiencies, and a group mean fixed gross efficiency. Energy expenditure was estimated from power using these different gross efficiencies and compared to measured energy expenditure during moderate- and hard-intensity constant-power and 2 variable-power cycling bouts. Estimated energy expenditures using individual or group mean power-specific gross efficiencies were not different from measured energy expenditure across all cycling bouts (p>0.05). To examine the intra-individual variability of the estimates, absolute difference scores (absolute value of estimated minus measured energy expenditure) were compared, where values closer to zero represent more accurate individual estimates. The absolute difference score using individual power-specific gross efficiencies was significantly lower compared to the other gross efficiencies across all cycling bouts (p<0.01). Significant and strong correlations (r≥0.97, p<0.001) were found across all cycling bouts between estimated and measured energy expenditures using individual power-specific gross efficiencies. In conclusion, using an individual's power-specific gross efficiency significantly improves their energy expenditure estimate across different power outputs.

Ten Days of Intermittent, Low-dose Carbon Monoxide Inhalation does not Significantly Alter Hemoglobin Mass, Aerobic Performance Predictors, or Peak-power Exercise Tolerance.

Carbon monoxide (CO) rebreathing procedures are used to assess hemoglobin mass (Hbmass) but recent evidence suggests that CO is a signaling molecule that may alter physiological functions. We examined the effects of 10 days of intermittent, low-dose CO inhalation on Hbmass, aerobic performance predictors, and peak-power exercise tolerance. 18 recreationally-active men were randomized to either CO or placebo inhalation groups in a single-blind, pre-post parallel-groups trial. Primary outcomes were assessed before and after an intervention period during which subjects inhaled a bolus of 1.2 ml kg(-1) CO or placebo (room air) for 30 s, once per day on 10 days over a 12-day period. Cycling tests were performed >16 h following CO inhalation to exclude acute effects of CO exposure. CO inhalation elevated carboxyhemoglobin by 4.4±0.4% (mean±SD) following each exposure. Compared to placebo, chronic CO inhalation did not significantly alter Hbmass (p=0.99), peak oxygen uptake (p=0.59), peak power output (p=0.10), submaximal oxygen uptake (p=0.91), submaximal RER (p=0.22), lactate threshold (p=0.65), or peak-power exercise tolerance (p=0.60). In conclusion, our data support the ability to perform repeated measurements of Hbmass using CO rebreathing over a 12-day period without altering physiological responses.

Acute, Low-dose CO Inhalation does not Alter Energy Expenditure during Submaximal Exercise.

Carbon monoxide, a gas known most widely for its toxic effects at high doses, is receiving increased attention for its role as a physiological signaling molecule and potential therapeutic agent when administered in low doses. We sought to quantify any changes to oxygen consumption and energy expenditure during submaximal exercise after low-dose CO inhalation. 9 active individuals completed 4 graded submaximal exercise tests, with each test occurring during a separate visit. For their first exercise test, subjects inhaled CO or room air (1.2 mL·kg(-1) body mass) in a randomized, subject-blind fashion. A second test was repeated 24 h later when the inhaled gas should have cleared the system. Subjects repeated study procedures with the alternate dose after a washout period of at least 2 days. Low-dose CO administration did not affect oxygen consumption or energy expenditure during submaximal exercise immediately or 24 h following its administration. Increases in heart rate, blood [lactate], and perceived exertion were observed following acute CO inhalation but these effects were absent after 24 h. The results of this study suggest that low-dose CO administration does not influence the energetics of submaximal exercise, but it acutely increases the relative intensity associated with absolute workloads below the lactate threshold.

Proteomic technologies in the study of kinases: novel tools for the investigation of PKC in the heart.

Recent developments in the field of protein separation allows for the analysis of qualitative and quantitative global protein changes in a particular state of a biological system. Due to the enormous number of proteins potentially present in a cell, sub-fractionation and the enrichment of specific organelles are emerging as a necessary step to allow a more comprehensive representation of the protein content. The proteomic studies demonstrate that a key to understand the mechanisms underlying physiological or pathological phenotypes lies, at least in part, in post-translational modifications (PTMs), including phosphorylation of proteins. Rapid improvements in proteomic characterization of amino acid modifications are further expanding our comprehension of the importance of these mechanisms. The present review will provide an overview of technologies available for the study of a proteome, including tools to assess changes in protein quantity (abundance) as well as in quality (PTM forms). Examples of the recent application of these technologies and strategies in the field of kinase signalling will be provided with particular attention on the role of PKC in the heart. Studies of PKC-mediated phosphorylation of cytoskeletal, myofilament and mitochondrial proteins in the heart have provided great insight into the phenotypes of heart failure, hypertrophy and cardioprotection. Proteomics studies of the mitochondria have provided novel evidences for kinase signalling cascades localized to the mitochondria, some of which are known to involve various isoforms of PKC. Proteomics technologies allow for the identification of the different PTM forms of specific proteins and this information is likely to provide insight into the determinants of morphological as well as metabolic mal-adaptations, both in the heart and other tissues.

Nucleated red blood cells in human fetal scalp capillary blood samples: a feasibility study.

OBJECTIVE: Elevated umbilical cord nucleated red blood cell (NRBC) counts have been suggested as a predictor of adverse perinatal outcome. We sought to evaluate the feasibility of obtaining fetal scalp capillary blood NRBC counts during labor and to assess their correlation with umbilical cord NRBC counts. METHODS: Fetal scalp capillary blood specimens were prospectively collected in laboring patients who underwent scalp sampling because of the presence of an abnormal fetal heart rate pattern. Matched umbilical cord blood samples were collected immediately after birth. Outcome measures were the feasibility of obtaining fetal scalp NRBC counts and their correlation with umbilical cord NRBC counts. RESULTS: Thirteen term singleton pregnancies formed the study population. In four patients, fetal scalp capillary blood sampling was performed twice. Of the attempts to evaluate fetal scalp capillary samples for NRBC counts, 16 out of 17 (94.1%) were successful. The mean fetal scalp capillary blood NRBC count per 100 white blood cells was 12.6 +/- 7.6 (+/- SD). Umbilical cord mixed, venous and arterial NRBC counts were 15.5 +/- 8.8, 13.4 +/- 10.7 and 12.6 +/- 10.7, with p = 0.09, p = 0.59 and p = 0.68, respectively, when compared to the corresponding scalp sample. The Spearman rank correlation between fetal scalp capillary samples and umbilical cord mixed, venous and arterial NRBC counts were r = 0.86, r = 0.92 and r = 0.95, respectively, with all p values < 0.001. CONCLUSION: Previous studies have established the clinical utility of umbilical cord NRBC counts. Our study demonstrated that it was possible to obtain NRBC counts from a fetal scalp capillary sample and that these counts correlated highly with umbilical cord NRBC counts. Future studies are needed to evaluate fetal scalp NRBC counts as a predictor of perinatal outcome.

Treatment with growth hormone and dexamethasone in mice transgenic for human islet amyloid polypeptide causes islet amyloidosis and beta-cell dysfunction.

Islet amyloid derived from islet amyloid polypeptide (IAPP) is a well-recognized feature of type II diabetes. However, the mechanism of islet amyloidogenesis is unknown. In vitro studies suggest that amino acid residues 20-29 in human, but not mouse, IAPP confer amyloidogenicity consistent with the absence of spontaneous islet amyloidosis in mice. Several clinical and in vitro studies suggest that increased synthetic rates of IAPP predispose to IAPP-amyloidosis. In the present study, we sought to test the hypothesis that pharmacological induction of insulin resistance in a mouse transgenic (TG) for human IAPP would induce islet amyloid and beta-cell dysfunction. TG and non-transgenic (N-TG) control mice were treated with both rat growth hormone (12 micrograms/day) and dexamethasone (0.24 mg/day) (dex/GH) or received no treatment for 4 weeks, after which animals were killed to examine islet morphology. Treatment with dex/GH caused hyperglycemia (7.3 +/- 0.4 vs. 5.2 +/- 0.1 mmol/l, TG vs. N-TG, P < 0.001) associated with a decreased plasma insulin concentration (595 +/- 51 vs. 996 +/- 100 pmol/l, TG vs. N-TG, P < 0.05) in TG versus control mice. Islet amyloid was induced in treated TG mice but not in control mice. Islet amyloid was identified in both intra- and extracellular deposits, the former being associated with evidence of beta-cell degeneration. We conclude that dex/GH treatment in mice TG for human IAPP induces IAPP-derived islet amyloid, hyperglycemia, and islet dysfunction. The present model recapitulates the islet morphology and phenotype of type II diabetes.

Correlations of plasma concentrations of B-cell polypeptides with pathologic features of insulinomas.

OBJECTIVE: To assess the correlations between plasma concentrations of b-cell polypeptides (insulin, C peptide) and size, multiplicity, and malignancy of insulinomas. METHODS: We retrospectively reviewed the medical records of 55 consecutively treated patients at our institution with surgically confirmed insulinoma. The 29 female and 26 male patients ranged from 13 to 77 years of age (median, 46). Plasma insulin, C peptide, proinsulin, and glucose concentrations were analyzed statistically in patients with benign and those with malignant insulinomas. RESULTS: Significant correlations were observed between plasma insulin and tumor size (r = 0.45; P = 0.001) and tumor volume (r = 0.41; P = 0.007) and between plasma C peptide and tumor size (r = 0.38; P = 0.004) and tumor volume (r = 0.33; P = 0.025). No differences between benign and malignant tumors were noted for plasma insulin, C peptide, glucose, nor tumor size or volume. No correlations were found between plasma insulin, C peptide, or glucose and number of tumors. CONCLUSION: The plasma levels of insulin and C peptide provide qualitative indications about the size of insulinomas.

Human islet amyloid polypeptide expression in COS-1 cells. A model of intracellular amyloidogenesis.

Non-insulin-dependent diabetes mellitus is characterized by concurrent loss of beta-cells and deposition of islet amyloid derived from islet amyloid polypeptide (IAPP). We have previously demonstrated that IAPP-derived amyloid forms intracellularly in humans with chronic excess insulin expression (eg, insulinoma and insulin receptor antibody-induced insulin resistance). To determine whether overexpression of IAPP results in intracellular amyloid in mammalian cells, we transfected COS cells with vectors expressing amyloidogenic human IAPP or non-amyloidogenic rat IAPP. Transfected COS-1 cells secreted comparable amounts of human IAPP and rat IAPP (2.1 to 2.8 nmol/L/48 hours). After 96 hours, 90% of cells expressing human IAPP contained amyloid fibrils and were degenerating or dead, whereas cells transfected with rat IAPP lacked amyloid and were viable. Thus, overexpression of human IAPP can result in intracellular amyloid formation that is associated with cell death, suggesting that intracellular amyloid may play a role in beta-cell loss in non-insulin-dependent diabetes mellitus.

Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood.

Transsphenoidal removal of pituitary adenomas has become the accepted treatment for Cushing's disease. As Cushing's disease is rare in childhood, few reports describe extended follow-up after transsphenoidal surgery for this disease in children. Twenty-two patients less than 19 yr of age were diagnosed with Cushing's disease by standard testing. All patients underwent transsphenoidal surgery (TSS) as primary treatment at Mayo Clinic between 1975 and 1990. Follow-up was available in all patients and averaged 6.7 yr. Adenomas were identified pathologically in 19 patients and visualized by the surgeon in the remainder. There was 1 macroadenoma. Ten patients are considered cured with a mean follow-up of 5.5 yr. Five patients had evidence of persistent disease within 6 months of TSS and required further treatment. Seven patients had remission lasting greater than 6 months with subsequent relapse (mean time to recurrence, 7.0 yr). In children treated with TSS for Cushing's disease, the rate of cure with extended follow-up is only approximately 50%. This rate is much lower than that in adults and may indicate that Cushing's disease is more aggressive in childhood. As TSS is associated with low morbidity, we feel it is still the treatment of choice for Cushing's disease in children.

Familial medullary thyroid cancer and prominent corneal nerves: clinical and genetic analysis.

A unique kindred manifesting medullary thyroid carcinoma and corneal nerve thickening without other aspects of the multiple endocrine neoplasia syndrome (MEN) was analyzed by linkage analysis using four highly polymorphic (CA)n repeat markers (sTCL-1, D10S141, ZNF22, and sJRH-1). Additionally, the RET protooncogene was examined for specific mutations by DNA sequence analyses in all affected family members. Screening of 11 family members spanning 4 generations revealed 7 subjects with corneal nerve thickening; of these subjects, 3 had abnormal pentagastrin-stimulated calcitonin studies, and these 3 subjects were each found to have C-cell hyperplasia or medullary thyroid carcinoma at surgery. Linkage analysis showed cosegregation of alleles (as defined by the above markers), with the presence of both corneal nerve thickening and medullary thyroid carcinoma/C-cell hyperplasia (maximum LOD score, 2.69; consistent with, but not proving linkage). DNA sequence analysis showed that none of the affected individuals had mutations in either exon 10 or 11, or in exon 16 of the RET protooncogene, regions where mutations have been described for MEN type 2A (MEN-2A) and MEN-2B families, respectively. Thus, compared to the defined syndromes of MEN-2A and MEN-2B, this kindred appears to represent a true clinical overlap syndrome whose genetic basis may be distinct from these two syndromes.

Pituitary adenomas in childhood and adolescence.

A clinicopathological study of 56 pediatric patients with non-ACTH-secreting pituitary adenomas removed by a transsphenoidal neurosurgical approach was undertaken to better define the clinical presentation, to assess demographic factors, to determine the immunohistochemical staining characteristics of the tumors, and to evaluate the outcome of transsphenoidal surgical treatment and other adjuvant therapies. A separate analysis of prolactinoma patients was performed. All tumors were confirmed histologically and immunophenotyped for pituitary hormones. Forty-one patients had tumors that stained for PRL alone, eight patients had tumors that stained for PRL and GH, six patients had plurihormonal adenomas, and one patient had a tumor that stained for glycoprotein hormones. No tumors contained GH alone. Macroadenomas exceeded microadenomas (1.4:1). There were no male patients with microadenomas of any type. Females outnumbered males (3.3:1). Patients presented most frequently with headache, menstrual dysfunction (in females), galactorrhea, and hypopituitarism. All but one of the patients with hypopituitarism at presentation had macroadenomas. Tumor staining characteristics did not always correlate well with clinical status, especially with regard to GH-containing tumors. Pediatric pituitary tumors did not appear to be more invasive or more aggressive than adult pituitary tumors, contrary to some previous reports. The patients with microadenomas had a 70% operative cure rate and a 65% long term cure rate; the recurrence rate for microadenoma patients was 25%. Macroadenoma patients had a 33% operative cure rate, a 55% long term cure rate, and a recurrence rate of 33%. Thus, microadenoma and macroadenoma patients had similar long term cure rates, but macroadenoma patients required more aggressive adjuvant therapy (second surgery, radiation, or bromocriptine) and had higher rates of hypopituitarism (52% of macroadenoma patients vs. 0% of microadenoma patients required long term hormone replacement).

Insulinoma in a patient with NIDDM.

OBJECTIVE: To confirm insulinoma as the cause of hypoglycemia in a patient with NIDDM and determine the frequency of the co-occurrence of these two conditions. RESEARCH DESIGN AND METHODS: The patient underwent an in-hospital prolonged fast (< or = 72 h), according to standard protocol, and an ultrasound examination of the pancreas. All cases of histologically confirmed insulinoma at this institution over the period of 1927-1992 were reviewed to determine the prevalence of pre-existent diabetes mellitus. RESULTS: After 10 h of fasting, plasma glucose was low (1.89 mM); plasma insulin (258 pM) and C-peptide (1.39 nM) were elevated in the absence of sulfonylurea in the plasma. An insulinoma detected by ultrasonography was removed surgically with subsequent reoccurrence of insulin-requiring diabetes. Among 313 cases of insulinoma confirmed at this institution, this patient is the only one with pre-existent diabetes mellitus. CONCLUSIONS: Insulinoma occurs extraordinarily rarely in patients with pre-existing NIDDM.

Changes in substance P and 5-HT binding in the spinal cord dorsal horn and lamina 10 after dorsolateral funiculus lesions.

The present study was undertaken to determine whether changes in receptor binding of substance P (SP) and 5-hydroxytryptamine (5-HT) occur in lumbar spinal cord laminae 2, 3, 4 and 10 following interruption of descending SP and 5-HT input. These transmitters and spinal cord regions have been implicated in nociceptive and visceral functions. Quantitative receptor binding autoradiography was used to assess the binding of 2 nM [3H]SP and 2 nM [3H]5-HT to lumbar spinal cord sections taken from normal rats and rats with unilateral thoracic dorsolateral funiculus (DLF) lesions. Postoperative survival times ranged from 1 to 28 days. Substance P binding was above normal in laminae 2 and 3 ipsilateral to the lesion and in contralateral lamina 2 at 1 day postoperatively (DPO), and declined thereafter, reaching below normal levels by 28 DPO. Substance P binding in lamina 10 was significantly above normal at 7 and 14 DPO, but not at 1 or 28 DPO. Binding of 5-HT was above normal at 7 DPO in lamina 2 ipsilateral to the lesion, lamina 3 contralaterally, and lamina 10 bilaterally. These increases were not sustained, however, and at 28 DPO 5-HT binding was significantly below normal in laminae 2-4 bilaterally. The bilateral effects seen in the present study are consistent with the bilaterality of descending thoracic DLF projections demonstrated by the Fink-Heimer method.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of 5-HT1 binding sites in cat spinal cord.

Quantitative analysis of high affinity [3H]5-HT binding to 5-HT1 receptors in the cervical, thoracic, lumbar, and sacral spinal cord of the cat revealed specific binding throughout the grey matter, with the highest levels of binding in laminae II and III, and the lowest levels in laminae I and VII. Relatively high levels were also observed in the thoracic intermediolateral cell column. There were no significant differences in the degree of binding between various segmental levels. Comparison of these data with published maps of 5-HT immunoreactivity reveals--with the exception of lamina I--a close correspondence between the degree of immunoreactivity and the degree of 5-HT binding. These results suggest that 5-HT plays an important role in a variety of spinal cord sensory, motor and autonomic functions.

Postcoital contraception: a family planning study.

The New Zealand Family Planning Association undertook a prospective study of Yuzpe's postcoital method of contraception (0.1 mg ethinyloestradiol and 1 mg d1-norgestrel taken within 72 hours of unprotected intercourse and repeated 12 hours later). The study also used pills containing levonorgestrel. Both pill formulations were equally effective. All participants were drawn from six family planning branches throughout the country. The study covered a period of one year. There were 909 participants with 8% lost to follow up. Strict criteria excluded women on medication or hormone therapy. The ages ranged from 11 to 43 years with 92% aged 19 years and under. Results revealed an overall failure rate of 2.3% and a significantly higher failure rate (4.49%) if the method was taken after 48 hours of unprotected intercourse and a significantly lower failure rate (1.22%) if taken before 12 hours of unprotected intercourse. Vomiting occurred in 17% but it did not affect the failure rate.

Open reduction of nasal fractures.

Open reduction of nasal fractures has been defined and discussed from a clinical standpoint. Specific advantages of the procedure are mentioned with the suggestion that perhaps more of these procedures should be performed. Reference is made to the authors' series of 788 cases, with analysis of type of injury, age group, and procedure performed.