PubMed Health⌕ Search

Biomedical subjects

R M Ross

Publications and source records attributed to R M Ross.

At least 19 recordsLinked to original sources
PubMed2006

Acute blockade by endothelin-1 of haemodynamic insulin action in rats.

AIMS/HYPOTHESIS: Plasma levels of endothelin-1 are frequently elevated in patients with hypertension, obesity and type 2 diabetes. We hypothesise that this vasoconstrictor may prevent full perfusion of muscle, thereby limiting delivery of insulin and glucose and contributing to insulin resistance. MATERIALS AND METHODS: The acute effects of endothelin-1 on insulin-mediated haemodynamic and metabolic effects were examined in rats in vivo. Endothelin-1 (50 pmol min(-1) kg(-1) for 2.5 h) was infused alone, or 30 min prior to a hyperinsulinaemic-euglycaemic insulin clamp (10 mU min(-1) kg(-1) for 2 h). Insulin clamps (10 or 15 mU min(-1) kg(-1)) were performed after 30 min of saline infusion. RESULTS: Endothelin-1 infusion alone increased plasma endothelin-1 11-fold (p < 0.05) and blood pressure by 20% (p < 0.05). Endothelin-1 alone had no effect on femoral blood flow, capillary recruitment or glucose uptake, but endothelin-1 with 10 mU min(-1) kg(-1) insulin caused a decrease in insulin clearance from 0.35 +/- 0.6 to 0.19 +/- 0.02 ml/min (p = 0.02), resulting in significantly higher plasma insulin levels (10 mU min(-1) kg(-1) insulin: 2,120 +/- 190 pmol/l; endothelin-1 + 10 mU min(-1)kg(-1) insulin: 4,740 +/- 910 pmol/l), equivalent to 15 mU min(-1) kg(-1) insulin alone (4,920 +/- 190 pmol/l). The stimulatory effects of equivalent doses of insulin on femoral blood flow, capillary recruitment and glucose uptake were blocked by endothelin-1. CONCLUSIONS/INTERPRETATION: Endothelin-1 blocks insulin's haemodynamic effects, particularly capillary recruitment, and is associated with decreased muscle glucose uptake and glucose infusion rate. These findings suggest that elevated endothelin-1 levels may contribute to insulin resistance of muscle by increasing vascular resistance and limiting insulin and glucose delivery.

Allopurinol↗
PubMed2001

Effects of dissolved carbon dioxide on the physiology and behavior of fish in artificial streams.

A new technology for treating waters contaminated with acid mine drainage involves the dissolution of limestone particles using carbon dioxide at pressures above ambient. Because of the fish health risks associated with episodes of high carbon dioxide levels in treated waters, we subjected three species of fish, brook trout (Salvelinus fontinalis), slimy sculpin (Cottus cognatus), and blacknose dace (Rhinichthys atratulus), to 24 h exposures of elevated dissolved carbon dioxide (CO2) at three levels, ranging from 1.0 (low) to 6.3 (high)%, under laboratory conditions. We measured blood physiological variables as well as behavior, including feeding responses, before, during, and after exposure. Physiological responses differed by species, but all species had elevated hematocrits after 1 h of exposure. Brook trout hematocritis were higher at medium and high levels of CO2 than in a control group (0.0% CO2) after 24 h of exposure. Slimy sculpin hematocrits were higher in medium- and high-level exposure groups than in controls after 1 h, but not after 24 h, of exposure. Blacknose dace hematocrits were higher in all three exposure groups than in controls after 1 h but only in medium-level exposure groups after 24 h. Brook trout plasma glucose was significantly higher in medium- and high-level exposure groups after 1 h, and in the high-level group after 24 h, than in controls. Slimy sculpin plasma glucose was not significantly different in elevated CO2 exposure groups from that of controls throughout exposure. Branchial ventilation was significantly greater in all species at elevated CO2 during exposure, indicating stress; however, no difference was observed between treatment and control groups of blacknose dace after 24 h, indicating acclimation. Pectoral fin beats and cough rates were not consistently related to CO2 exposure throughout the study. Brook trout had the longest lasting reaction to stress at lower levels of CO2 among the three species tested. Many of the 11 observed behavioral variables, related to swimming, feeding, social, and illness factors, were affected by elevations of dissolved CO2. Two to seven behavioral variables (18-64% of those measured) were affected by treatment level of dissolved CO2 with a trend by species for the number of variables affected: brook trout > blacknose dace > slimy sculpin. However, behavioral sensitivity to treatment level was greatest in blacknose dace. Recovery to pre-treatment activity rates for most behavior patterns (including feeding) was observed 24 h after cessation of exposure in all three species. Recovery was independent of treatment level, was most rapid in blacknose dace, and was slowest in brook trout. Overall, slimy sculpin was least affected behaviorally by elevated CO2. Although all three species showed stress response and changes in behavior at moderate levels of CO2 (> or = 2%), brook trout and blacknose dace showed evidence of ability to avoid harmful CO2 levels by swimming out of affected waters, whereas the slimy sculpin showed minimal behavioral changes despite remaining in place during exposure. Thus, predation risk and other sources of mortality seem minimal in the event of technological malfunction at a stream treatment site involving the use of CO2 under pressure.

Animals↗
PubMed1999

Identification of a mutation cluster in mevalonate kinase deficiency, including a new mutation in a patient of Mennonite ancestry.

Mevalonate kinase (MKase) deficiency (MKD) is a rare autosomal recessive disorder in the pathway of cholesterol and nonsterol isoprenoid biosynthesis. Thus far, two disease-causing missense alleles have been identified, N301T and A334T. We report four additional mutations associated with MKD: L264F, T243I, L265P, and I268T, the last found in a patient of Mennonite ancestry. Electrophoretic analysis of bacterially expressed wild-type and mutant MKase indicated that I268T and T243I mutants produced normal or somewhat reduced amounts of MKase protein; conversely, L264F and L265P mutations resulted in considerably decreased, or absent, MKase protein. Immunoblot analysis of MKase from all patients suggested that the MKase polypeptide was grossly intact and produced in amounts comparable to control levels. Three mutations resulted in significantly diminished MKase enzyme activity (<2%), whereas the I268T allele yielded approximately 20% residual enzyme activity. Our results should allow more-accurate identification of carriers and indicate a mutation "cluster" within amino acids 240-270 of the mature MKase polypeptide.

Alleles↗
PubMed1999

A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans.

We cloned the dbl-1 gene, a C. elegans homolog of Drosophila decapentaplegic and vertebrate BMP genes. Loss-of-function mutations in dbl-1 cause markedly reduced body size and defective male copulatory structures. Conversely, dbl-1 overexpression causes markedly increased body size and partly complementary male tail phenotypes, indicating that DBL-1 acts as a dose-dependent regulator of these processes. Evidence from genetic interactions indicates that these effects are mediated by a Smad signaling pathway, for which DBL-1 is a previously unidentified ligand. Our study of the dbl-1 expression pattern suggests a role for neuronal cells in global size regulation as well as male tail patterning.

Amino Acid Sequence↗
PubMed1996

An effect of magnesium on neuromuscular function in parturients.

STUDY OBJECTIVE: To determine the effects of magnesium sulfate on neuromuscular transmission in parturients. DESIGN: Open-label, clinical study. SETTING: Preeclamptic patients at a university-affiliated hospital. PATIENTS: 12 pregnant patients, ages 18 to 40 years, with preeclampsia or entering preterm labor. INTERVENTIONS: Patients were treated with magnesium sulfate. Train-of-four (TOF) recordings of the adductor pollicis muscle were obtained before and 30 minutes after the magnesium sulfate infusion. MEASUREMENTS AND MAIN RESULTS: Each contractile response in the control TOF showed an increase in the tension developed in response to supramaximal stimulation. The TOF responses after magnesium sulfate did not demonstrate this phenomenon, but rather developed fade. The T4/T1 ratios ranged from 0.72 to 0.92. CONCLUSIONS: In this patient population, clinically relevant infusions of magnesium sulfate produced significant changes in neuromuscular transmission as manifested by loss of treppe phenomenon and diminished TOF response to ulnar nerve stimulation.

Adolescent↗
PubMed1996

The differential regulation of the circulating levels of the insulin-like growth factors and their binding proteins (IGFBP) 1, 2 and 3 after elective abdominal surgery.

OBJECTIVES: Patients undergoing abdominal surgery often suffer from morbidity associated with increased protein catabolism. Therapeutic recombinant human insulin-like growth factor (rhIGF)-I has been proposed as a means of reversing this process. As IGFBPs modulate the bioavailability of the IGFs, we have studied the changes in the circulating levels of these peptides during surgery. DESIGN: Patients undergoing elective intestinal surgery were recruited prospectively. Blood samples were taken before, during and after surgery. Standard anaesthetic techniques were used. METHODS: Twelve adults (aged 30-70 years; 9 female, 3 male) undergoing surgery were studied. Serum was taken before premedication (preop), end of surgery (end surg), 2 h, 6 h post surgery, on days 1-4, 7, 10 and 14, and on recovery at 6 weeks. MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, insulin and C-peptide were measured by radioimmunoassay. IGFBP profiles were also assessed by Western ligand blot (WLB). Samples taken preop and at 2 days were separated by fast-phase liquid chromatography (FPLC) using a Superose 12 column under neutral conditions (pH 7.4), and the fractions were analysed subsequently by WLB and immunoblot using a specific IGFBP-3 antiserum. RESULTS: IGF-I fell rapidly during surgery from 170 +/- 21 (preop) to 133 +/- 14 micrograms/l (end surg) (P < 0.05). The magnitude of this fall could not be explained by haemodilution. IGF-I levels then fell further to a nadir of 103 +/- 10 micrograms/l at day 4 (P < 0.05). IGF-II fell from 580 +/- 46 (preop) to 397 +/- 38 micrograms/l (day 2). Both IGF-I and IGF-II recovered to preop levels at 6 weeks (205 +/- 14 micrograms/l and 623 +/- 30 micrograms/l respectively). IGFBP-3 levels fell similarly from 4.46 +/- 0.45 to 3.2 +/- 0.3 mg/l (end surg) and to a nadir of 2.66 +/- 0.19 mg/l at day 2. There was a close correlation between IGFBP-3 levels and the sum of IGF-I and IGF-II levels before surgery (r = 0.9, P < 0.01) and this was maintained throughout the post-operative period (mean correlation coefficient of 0.86 +/- 0.02, P < 0.05). On days 2 and 3 there was a small but significant increase in the ratio between serum IGF-I and IGFBP-3 levels compared with the preop ratio (P < 0.05 and < 0.005, respectively). WLB demonstrated almost complete absence of IGFBP-3 by day 2. This discrepancy between RIA and WLB analysis of IGFBP-3 suggested the presence of IGFBP-3 protease activity between days 1 and 4. This was confirmed by WLB and immunoblot analyses of samples taken 2 days after surgery. The decrease in IGFBP-3 on WLB was shown to be associated with an increase in the proteolytically cleaved fragments of IGFBP-3. These fragments following FPLC were detected in the high molecular weight fractions, suggesting that the fragments were still able to form the high molecular weight IGFBP-3/ALS complex which is thought to form only when IGF is bound by IGFBP-3. IGFBP-1 levels rose during surgery (mean duration of surgery was 125 minute) from 18 +/- 3 (preop) to 51 +/- 12 micrograms/l (end surg) (P < 0.05). This rise in IGFBP-1 paralleled increases in insulin from 7.3 +/- 1.0 to 20.8 +/- 7.5 mU/l and glucose from 4.6 +/- 0.3 to 8.7 +/- 1.2 mmol/l. IGFBP-1 levels then fell to basal values by 6 hours. IGFBP-2, in contrast, fell slightly during surgery from 636 +/- 14 to 599 +/- 96 mg/l and then returned to basal levels by 6 hours. CONCLUSION: After major surgery there are complex and diverse changes in the IGFs and IGFBPs. The effect of these changes on IGF bioavailability may significantly affect the therapeutic potential of IGF-I in this setting.

Abdomen↗
PubMed1995

Cardiac enzymes in patients undergoing caesarean section.

Some of the changes reported in the ECG of parturients undergoing Caesarean section are suggestive of myocardial ischaemia. This study determined serum CK total and the isoenzyme CK-MB levels in 21 patients during and after Caesarean section under epidural anaesthesia. Twenty patients complained of chest pain, discomfort and pressure, while 12 had ST segmental depression. Although the total CK activity in ten patients was elevated, CK-MB activity in all patients was negative. The electrocardiographic changes were rate-related and occurred at the time pressure was placed upon the upper abdomen and lower thoracic cage by the surgeon to facilitate Caesarean delivery. The data from this study demonstrate that no myocardial injury as measured by CK-MB activity occurs in parturients undergoing Caesarean delivery despite the complaint of chest pain, discomfort and pressure, and ST changes in the ECG.

Abdomen↗
PubMed1995

Changes in aerobic power of men, ages 25-70 yr.

This study quantified and compared the cross-sectional and longitudinal influence of age, self-report physical activity (SR-PA), and body composition (%fat) on the decline of maximal aerobic power (VO2peak). The cross-sectional sample consisted of 1,499 healthy men ages 25-70 yr. The 156 men of the longitudinal sample were from the same population and examined twice, the mean time between tests was 4.1 (+/- 1.2) yr. Peak oxygen uptake was determined by indirect calorimetry during a maximal treadmill exercise test. The zero-order correlations between VO2peak and %fat (r = -0.62) and SR-PA (r = 0.58) were significantly (P < 0.05) higher that the age correlation (r = -0.45). Linear regression defined the cross-sectional age-related decline in VO2peak at 0.46 ml.kg-1.min-1.yr-1. Multiple regression analysis (R = 0.79) showed that nearly 50% of this cross-sectional decline was due to %fat and SR-PA, adding these lifestyle variables to the multiple regression model reduced the age regression weight to -0.26 ml.kg-1.min-1.yr-1. Statistically controlling for time differences between tests, general linear models analysis showed that longitudinal changes in aerobic power were due to independent changes in %fat and SR-PA, confirming the cross-sectional results.

Adipose Tissue↗
PubMed1990

Prediction of functional aerobic capacity without exercise testing.

The purpose of this study was to develop functional aerobic capacity prediction models without using exercise tests (N-Ex) and to compare the accuracy with Astrand single-stage submaximal prediction methods. The data of 2,009 subjects (9.7% female) were randomly divided into validation (N = 1,543) and cross-validation (N = 466) samples. The validation sample was used to develop two N-Ex models to estimate VO2peak. Gender, age, body composition, and self-report activity were used to develop two N-Ex prediction models. One model estimated percent fat from skinfolds (N-Ex %fat) and the other used body mass index (N-Ex BMI) to represent body composition. The multiple correlations for the developed models were R = 0.81 (SE = 5.3 ml.kg-1.min-1) and R = 0.78 (SE = 5.6 ml.kg-1.min-1). This accuracy was confirmed when applied to the cross-validation sample. The N-Ex models were more accurate than what was obtained from VO2peak estimated from the Astrand prediction models. The SEs of the Astrand models ranged from 5.5-9.7 ml.kg-1.min-1. The N-Ex models were cross-validated on 59 men on hypertensive medication and 71 men who were found to have a positive exercise ECG. The SEs of the N-Ex models ranged from 4.6-5.4 ml.kg-1.min-1 with these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Fat embolism after liposuction.

We present a case of adult respiratory distress syndrome (ARDS) after extensive liposuction. On the basis of fever, tachypnea, hypoxia, and ARDS occurring within 48 hours after surgery without evidence of cardiogenic pulmonary edema or sepsis, the etiology is believed to be fat embolism. Although liposuction is generally an effective and safe procedure, awareness of this life-threatening complication is important in order to institute prompt and appropriate treatment. Fat embolism must be differentiated from thromboembolism, as the treatment is different, and heparin is not indicated. It is recommended that training standards and guidelines be devised in order to reduce morbidity and mortality associated with this procedure.

Abdomen↗
PubMed1987

Limitation of deuterium labelled methoximes as internal standards in the mass spectral analysis of prostaglandins.

A reported method for the preparation of d3-methoxime derivatives as internal standards for prostaglandin assays by gas chromatography-mass spectrometry was evaluated. Sample derivatization resulted in 1.5-86% exchange of the d3-methoxime in a series of prostaglandins. Exchange was minimal when the methoxime was on the 5-membered ring; whereas, acyclic methoximes exhibited extensive exchange. Induced strain energy due to the steric interaction of the hydroxyl group and the C13-C20 alkyl side chain with the gem-dimethoxylamine transition state is offered as an explanation for the unusual stability of PGE2. The use of 18O exchange of the carboxylic acid function is presented as an alternative for the preparation of unavailable labelled eicosanoids.

Deuterium↗
PubMed1986

Delayed life-threatening hemothorax associated with rib fractures.

We present two cases of delayed, massive, life-threatening hemothorax due to intercostal hemorrhage in association with fractured ribs and severe blunt chest trauma (SBCT), a combination we have not seen described in the literature. Blunt chest trauma is not benign. Significant intrathoracic injuries are frequent although usually not life threatening. However, associated extrathoracic injuries are also common and much more lethal. Most cases of hemo- and pneumothorax associated with SBCT can be treated without thoracotomy. However, rapid blood loss requires immediate open thoracotomy and surgical attention. Several days of observation in hospital may be required for patients with SBCT and fractured ribs even without any other obvious intra- or extra-thoracic injuries. Vigorous activity or chest physical therapy may be dangerous during the first several days after the injury.

Accidents, Occupational↗