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Biomedical subjects

H Welch

Publications and source records attributed to H Welch.

At least 19 recordsLinked to original sources
PubMed2005

Elucidating determinants of the plateau in oxygen consumption at VO2max.

BACKGROUND: A plateau in oxygen consumption (VO2) is the primary means of confirming that maximal oxygen uptake (VO2max) is attained during incremental exercise to fatigue. However, it is still unresolved what causes expression of a plateau in VO2 at the end of incremental exercise. OBJECTIVES: To elucidate incidence and identify determinants of the VO2 plateau in subjects of varying fitness. METHODS: Thirty subjects (mean (SD) age and VO2max 26.9 (9.8) years and 3.4 (0.8) litre/min respectively) were separated into three groups: endurance trained (ET; n = 9), recreationally active (Rec; n = 11), and strength/sprint trained (STR; n = 10). During three separate visits, subjects completed incremental treadmill exercise during which breath by breath gas exchange data were obtained. Body composition was measured using a three site skinfolds model. Force production of the knee extensors and flexors was assessed using isokinetic dynamometry. RESULTS: VO2max was significantly higher (p < 0.05) in the ET group vs STR and Rec. The change in VO2 (DeltaVO2) at VO2max was not different (p > 0.05) in the ET group (33.0 (27.3) ml/min) compared with the Rec group (30.3 (24.1) ml/min) and the STR group (44.4 (23.8) ml/min). No correlations (p > 0.05) were evident between DeltaVO2 at VO2max and VO2max (r = 0.05), fat-free mass (r = 0.12), and muscular strength (r = -0.12). CONCLUSIONS: The incidence of a plateau in VO2 at VO2max (from correlation data) is not due to factors related to training status or physical fitness of subjects, but is altered by analysis and interpretation of gas exchange data.

Adolescent↗
PubMed1999

The effect of anastrozole on the pharmacokinetics of tamoxifen in post-menopausal women with early breast cancer.

Thirty-four post-menopausal women with early breast cancer who had received 20 mg tamoxifen once daily as adjuvant therapy for at least 10 weeks participated in a randomized, double-blind, parallel-group, multicentre trial. The primary aim of the trial was to determine the effect of anastrozole upon tamoxifen pharmacokinetics, with secondary aims of assessing the tolerability of the two drugs in combination and whether or not tamoxifen had any effect upon the oestradiol suppression seen with anastrozole. Patients were randomized to receive either 1 mg anastrozole (16 patients) or matching placebo (18 patients) once daily on a double-blind basis for 28 days. No significant difference (P = 0.919) was observed in serum tamoxifen concentrations between the anastrozole and placebo groups during the trial. The serum concentration of oestradiol was significantly suppressed (P < 0.0001) in patients co-administered anastrozole compared with placebo in the presence of tamoxifen, confirming that anastrozole remained an effective suppressant of oestradiol in the presence of tamoxifen. The combination of tamoxifen and anastrozole was well tolerated, with very little difference in side-effects reported between anastrozole and placebo. In conclusion, the results of this study confirm that anastrozole does not affect the pharmacokinetics of tamoxifen when the two drugs are given in combination to post-menopausal women with early breast cancer. In addition, the oestradiol suppressant effects of anastrozole appear unaffected by tamoxifen.

Anastrozole↗
PubMed1998

PI 3-kinase.

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Phosphatidylinositol 3-Kinases↗
PubMed1998

Protein kinase B and rac are activated in parallel within a phosphatidylinositide 3OH-kinase-controlled signaling pathway.

The GTPase Rac and the protein kinase B (PKB) are downstream targets of phosphatidylinositide 3OH-kinase in platelet-derived growth factor-stimulated signaling pathways. We have generated PAE cell lines inducibly expressing mutants of Rac. Use of these cell lines suggests that Rac is involved in both platelet-derived growth factor-stimulated membrane ruffling and the activation of p70(S6K) but not in the activation of PKB. Furthermore, expression of constitutively active alleles of PKB in PAE cells suggests that PKB is able to regulate the activity of p70(S6K) but not the cytoskeletal changes underlying membrane ruffling. Thus, our results indicate that Rac and PKB are on separate pathways downstream of phosphatidylinositide 3OH-kinase in these cells but that both of these pathways are involved in the regulation of p70(S6K).

Cell Line↗
PubMed1998

Expression of azurophil and specific granule proteins during differentiation of NB4 cells in neutrophils.

Neutrophils contain several populations of secretory granules with characteristic sets of proteins. Granule proteins are sorted into their respective granule types by temporal regulation of their expression during cell differentiation and/or by specific targeting signals. We investigated the expression of some granule proteins in human promyelocytic NB4 cells. Like other myeloid cell lines which can be differentiated into neutrophils, NB4 cells lack the specific-granule population. We report here that, nevertheless, they express the specific-granule matrix protein lactoferrin, when differentiated with retinoic acid. Lactoferrin and the azurophil-granule protein beta-glucuronidase were simultaneously expressed, whereas myeloperoxidase expression had stopped, showing that azurophil-granule proteins are not all produced concomitantly. Cell fractionation by Percoll gradient revealed that while beta-glucuronidase co-fractionated with myeloperoxidase, lactoferrin was mostly contained in a vesicular compartment free of markers for azurophil granules, plasma membrane, and Golgi. This vesicular compartment was not implicated in regulated exocytosis since it was not mobilized by secretagogues, which, in parallel, induced the release of myeloperoxidase. Furthermore, the specific granule-membrane protein cytochrome b558 also became expressed during NB4-cell differentiation. However, it did not co-localize with lactoferrin but was present in the plasma-membrane fraction. Therefore, differentiation of NB4 cells with retinoic acid leads to the expression of specific- and azurophil-granule proteins and provides a unique cell line model to study the mechanisms involved in the sorting of azurophil- and specific-granule proteins.

Biomarkers↗
PubMed1997

Lyn and Fgr are activated in distinct membrane fractions of human granulocytic cells.

We have previously shown that the src-family protein-tyrosine kinase Hck is localized on the azurophil granules of human granulocytes, translocates towards the phagosomes during phagocytosis of opsonized zymosan and is activated during this process. Hck is also activated upon cell stimulation with the calcium ionophore A23187, but not with PMA or the chemotactic peptide fMLP. Here, we investigated whether the src-family kinases Lyn and Fgr are activated under the same conditions. Upon stimulation of human neutrophils or retinoic acid-differentiated NB4 cells with fMLP, only Lyn is activated. Cell stimulation with opsonized zymosan or A23187 leads to simultaneous activation of Lyn and Fgr. In cell fractionation experiments with differentiated NB4 cells, the kinases show a similar subcellular localization: Both co-fractionate quantitatively with plasma-membrane marker in two fractions that sediment at 11000 g and 200000 g. Lyn is selectively activated in the 200000 g fraction, whereas Fgr is activated in the 11000 g fraction and distinct sets of tyrosine phosphorylated proteins are found in these fractions. The results suggest that these kinases exert their functional roles in distinct cellular compartments in human granulocytic cells.

Blotting, Western↗
PubMed1997

Hck is activated by opsonized zymosan and A23187 in distinct subcellular fractions of human granulocytes.

Regulation of neutrophil responses is known to involve tyrosine phosphorylation. Hck, a major neutrophil protein-tyrosine kinase, becomes expressed during differentiation of human promyelocytic NB4 cells into neutrophil-like cells. Hck is mainly localized in a secretory granule-enriched cell fraction, but it is also present in a granule-free membrane fraction and the cytosol. Hck is rapidly and transiently activated upon stimulation of differentiated NB4 cells or human neutrophils with serum-opsonized zymosan or the calcium ionophore A23187, but not by phorbol 12-myristate 13-acetate. In NB4 cells, Hck is also weakly activated by fMet-Leu-Phe. Cell fractionation showed that opsonized zymosan and A23187 induce Hck activation in distinct subcellular fractions. Both stimuli activate Hck in the secretory granule-enriched fraction, but only A23187 activates the kinase in the granule-free membrane fraction. Our results suggest that Hck might regulate early signal transduction events induced by opsonized zymosan and A23187, and that the different subcellular fractions of Hck might serve discrete functions, one of which could be regulation of the degranulation response.

Calcimycin↗
PubMed1997

Maternal experience during epidural or combined spinal-epidural anesthesia for cesarean section: a prospective, randomized trial.

UNLABELLED: Epidural anesthesia (EA) and combined spinal-epidural anesthesia (CSEA) are popular anesthetic techniques for elective cesarean section. A randomized, blind study was conducted to compare maternal experiences during these regional anesthetics. EA was established using alkalinized 2% lidocaine with epinephrine and fentanyl, whereas spinal anesthesia was performed using 2.5 mL hyperbaric 0.5% bupivacaine and fentanyl via a single-space CSEA approach. Both patients and observers were blinded to the anesthetic technique allocation. One hundred twenty patients were enrolled; 6 were withdrawn (Group EA, n = 55; Group CSEA, n = 59). Of the two techniques, CSEA was associated with earlier onset times (P < 0.001), more intense motor block (P < 0.05), and greater ephedrine use (P < 0.01). Anxiety was significantly lower (P < 0.05) and satisfaction was higher (P < 0.05) before starting surgery with CSEA. Pain scores were lower pre- and intraoperatively with CSEA, a difference that became significant during block placement and at delivery (P < 0.05). There were no differences between groups in the incidence or severity of hypotension and nausea or analgesic supplementation rate; or for postoperative assessments of intraoperative pain, anxiety and satisfaction, and postpartum backache and headache. We conclude that maternal conditions and experience were good with both methods, although CSEA conferred several minor advantages. IMPLICATIONS: Epidural and combined spinal-epidural anesthesia are often used for elective cesarean sections. Although the combined spinal-epidural anesthetic technique conferred minor advantages, both techniques were associated with low anesthetic failure rates, good operative conditions, and high maternal satisfaction levels.

Adult↗
PubMed1996

Nonreceptor Protein-Tyrosine Kinases in Neutrophil Activation

Nonreceptor protein-tyrosine kinases are involved in the regulation of almost all neutrophil responses such as adhesion, chemotaxis, priming, oxidative burst, and degranulation. Here, we show that phagocytosis is also regulated by protein-tyrosine kinase activity. Using various protein-tyrosine kinase inhibitors, we further demonstrate that opsonized zymosan-induced degranulation of specific and azurophil granules is regulated by protein-tyrosine kinase activity, whereas phorbol ester-induced degranulation is not. Several of the nonreceptor protein-tyrosine kinases involving in neutrophil signal transduction are known, including Fgr, Hck, Lyn, Yes, and Syk. Among these, Hck and Fgr are localized on the azurophil and specific granules, suggesting the involvement of these two protein-tyrosine kinases in the regulation of degranulation. In this report, we characterize some of the molecular properties of Hck and Fgr. We discuss the methods generally used for the measurement of protein-tyrosine kinase activities in neutrophils highlighting precautions against proteolysis. In addition, we show that in subcellular fractions of retinoic acid-differentiated neutrophil-like NB4 cells, the 59- and 61-kDa forms of Hck are attached to the membranes of their respective compartments by different mechanisms. Finally, we discuss the functional roles of protein-tyrosine kinases in the regulation of neutrophil activation and speculate on the importance of their subcellular localization.

Journal Article↗
PubMed1996

Nurse midwives as primary care providers for women.

As we approach the 21st century, the prospect of a new healthcare system in the United States should prompt us to reopen the question of who can best meet the healthcare needs of women. Nurse midwives are advanced practice nurses educated in the field of primary health care for essentially normal women and newborns. Their focus is wellness and health education. Once patients are introduced to the concept of a nurse practitioner and the services provided, the majority are satisfied with the quality of the care received. Evidence suggests that women, if given a choice, prefer the ministrations of a female practitioner over that of a male for their intimate healthcare needs. As a predominantly female group, nurse midwives are an excellent source of qualified providers for women. In this article, the cost effectiveness of nurse practitioner care and the issue of provider gender are discussed. A case for the utilization of nurse midwives as primary healthcare providers for women is presented.

Cost-Benefit Analysis↗
PubMed1994

Correlation of venous noninvasive tests with the Society for Vascular Surgery/International Society for Cardiovascular Surgery clinical classification of chronic venous insufficiency.

PURPOSE: Noninvasive tests for the evaluation of chronic venous insufficiency (CVI) include quantitative photoplethysmography (QPG), air plethysmography, and duplex ultrasonography measurement of valve closure time (VCT). These tests have been shown to accurately identify the presence of CVI, define the disease, and locate the involved segments. However, the correlation of noninvasive assessment of CVI with the clinical severity (Society for Vascular Surgery/International Society for Cardiovascular Surgery staging) has not been addressed critically. METHOD: During an 18-month period, 74 limbs were prospectively evaluated with clinical examination, air plethysmography, QPG and duplex ultrasonography. RESULTS: We studied 52 patients with a mean age of 46 years. There were 14 stage 0 limbs, 14 stage 1, 15 stage 2, and 31 stage 3. We found significant differences (p < 0.05) between normal limbs and those with CVI only by VCT and QPG. There were also marked trends toward worsening mean values for reflux (VCT, QPG, and venous filling index) and venous hypertension (residual volume fraction) between stages 0 to 1, and 1 to 2; however, there was a large degree of overlap between all groups. No test discriminated stage 2 from 3. Assessment of calf muscle pump function with ejection fraction showed no difference between any groups. CONCLUSION: The Society for Vascular Surgery/International Society for Cardiovascular Surgery criteria for CVI staging distinguishes ulcerated limbs (stage 3) from those with nonulcerating skin changes (hyperpigmentation, brawny edema, and subcutaneous fibrosis) (stage 2). However, we were not able to distinguish these groups by available noninvasive methods. This may imply that these tests are not accurate enough or that the progression from lipodermatosclerosis to frank ulceration is not accounted for by large-vessel hemodynamic changes, but rather by microcirculatory alterations.

Adult↗
PubMed1992

Routine postendarterectomy duplex surveillance: does it prevent late stroke?

Our recent finding that less than 50% of late postendarterectomy strokes are related to recurrent carotid stenosis led us to question the utility of routine postendarterectomy duplex surveillance (RpCEADS) in the prevention of late stroke. To evaluate our RpCEADS program, we reviewed our postoperative duplex studies and correlated their results with clinical data. A total of 1053 postendarterectomy scans was carried out on 348 carotid arteries (258 patients) (3.0 +/- 0.1 studies/artery) during an average follow-up of 52.6 (+/- 2.3) months. Less than 50% of recurrent carotid stenosis was documented throughout follow-up in 292 (83.9%) of 348 arteries. Recurrent carotid stenosis of greater than 50% or occlusion of either the common or internal carotid artery was noted in the remaining 56 arteries (16.1%). Of the 56 duplex-detected recurrent stenoses, only two (3.6%) resulted directly in an unheralded stroke, whereas eight (14.3%) underwent prophylactic reoperation, eight (14.3%) resulted in transient ischemia requiring reoperation, eight (14.3%) occluded without causing stroke, and 29 (51.8%) remained asymptomatic and did not progress to occlusion. Assuming that each of our eight patients who underwent prophylactic reoperation would have had a stroke if operation had not been carried out and our two unheralded strokes could have been prevented with more rigorous follow-up, RpCEADS might have prevented late stroke related to 10 (2.9%) of 348 arteries in 10 (3.9%) of 258 patients after surgery. All other cases of duplex-detected recurrent carotid stenosis or occlusion were asymptomatic or manifest by transient cerebral ischemia. Therefore RpCEADS cannot be justified as a means of preventing late strokes related to recurrent stenosis.

Carotid Stenosis↗
PubMed1987

Factors affecting the level of kanamycin resistance in transformed sunflower cells.

A 230 base pair DNA segment containing the sequences 5' to the 700 to 750 nucleotide (nt) transcript 7' (ORF 3; RF Barker, KB Idler, DV Thompson, JD Kemp 1983 Plant Mol Biol 2: 335-350) of the octopine tumor inducing plasmid pTiA6 has been isolated. This region has (a) 180 base pairs of DNA upstream of the TATA box, (b) the start of RNA synthesis, and (c) the entire 5' untranslated region of the gene. We have fused this presumed promoter fragment to the neomycin phosphotransferase II (NPTII) gene from Tn5 in a plant expression cassette. After recombination into a tumor inducing plasmid delivery plasmid, this cassette confers selectable kanamycin resistance to transformed sunflower cells. Removal of the out-of-frame ATG in the 5' leader sequence of the NPTII gene by two different modifications increased both the levels of NPTII enzyme activity and the ID(50) for kanamycin in the tumor cells. The promoter region of the transcript 7 gene gives levels of kanamycin resistance equivalent to the nopaline synthase promoter and octopine synthase promoter when used in the same constructions and assayed in the same tissues.

Journal Article↗
PubMed1986

Complications of carotid endarterectomy. A military hospital experience.

The Naval Hospital Oakland (NHO) carotid study is a review of the morbidity and mortality of an 8-year experience of 201 consecutive carotid endarterectomies (164 patients). Arteriographic findings, risk factors, method of patient management, and all major and minor complications are discussed. Patient groups are categorized by indication for surgery and by the Mayo Clinic classification of Sundt. A credentialed attending surgeon assisted a senior general surgery resident (81.6%) or performed the operation himself (18.4%). Resident and staff adverse occurrences are compared. Complications in the NHO study were present in 35.8 per cent of cases (8.9% major). Elimination of myocardial infarction and transient ischemic attacks reduced this to 4 per cent. The experience is compared to one in a university setting, a Veteran Administration study, community hospital studies, and a study performed in another major military medical center.

Adult↗
PubMed1982

Prophylactic carotid endarterectomy for asymptomatic bruit. A look at cardiac risk.

We assessed the influence of preoperative cardiac risk factors in 57 patients undergoing 70 prophylactic carotid endarterectomies (PCE) and found that: (1) 47 (83%) had at least one cardiac risk factor and (2) nine of 15 deaths occurring in the late follow-up period (40 to 120 months) were due to cardiac causes. Perioperatively, one patient sustained a mild stroke. Although the cumulative stroke-free occurrence rate was kept to less than 6% over the five-year period, cardiac morbidity and mortality greatly influenced the quality of life after PCE. Therefore, PCE is suggested only for patients who have minimal preoperative cardiac risk factors or for those patients whose cardiac risk factors can be improved by medical therapy.

Aged↗
PubMed1979

Failure of carotid stump pressures. Its incidence as a predictor for a temporary shunt during carotid endarterectomy.

A total of 289 carotid endarterectomies were performed in 204 patients. A decision to place a temporary shunt during carotid endarterectomy in this series was made entirely on the basis of intraoperative EEG monitoring. Retrospectively, the correlation between stump pressures and the results of intraoperative EEG monitoring in each case was determined. Evidence of ischemia developed in 6% of the total series on intraoperative EEG monitoring despite a stump pressure of greater than 50 mm Hg. The degree of disagreement between stump pressure and EEG varied according to clinical category in this series. In those endarterectomies performed for completed stroke, all cases requiring shunting had stump pressures less than 50 mm Hg. In those cases performed for symptoms of vertebral basilar insufficiency, however, 77% of the cases requiring an intraoperative shunt had stump pressures greater than 50 mm Hg. A review of the complication rate in the various study groups indicates that the use of intraoperative EEG is a safe indicator of cerebral ischemia during carotid endarterectomy regardless of stump pressure.

Blood Pressure↗