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Biomedical subjects

M L Hughes

Publications and source records attributed to M L Hughes.

36 records · Page 2Linked to original sources
PubMed1999

Relationship between EABR thresholds and levels used to program the CLARION speech processor.

The purpose of this study was 1) to describe the relationship between electrically evoked auditory brain stem response (EABR) thresholds and the behavioral measures needed to program the speech processor of the CLARION Multi-Strategy Cochlear Implant, and 2) to determine whether the relationship between EABR threshold and the behavioral levels used to program the Clarion device was correlated with the temporal integration abilities of these subjects. The EABR thresholds, psychophysical thresholds, and the Clarion speech processor programming levels were recorded from 29 postlingually deafened adults. The mean EABR thresholds approximated most comfortable levels (M levels) for the programming stimulus. However, intrasubject variability was substantial. Significant intrasubject variability in temporal integration also was observed. Correlations were found between the ability of a cochlear implant user to perform temporal integration and the relationship between his or her EABR threshold and the threshold for the programming stimulus.

Adult↗
PubMed1999

Persistent hypophyseal (craniopharyngeal) canal.

Two cases with a broad persistent hypophyseal canal connecting pituitary fossa and nasopharynx are presented. Both had nasopharyngeal surgery in early childhood and presented later with hypopituitarism. Coronal CT demonstrated the defects with no visible pituitary tissue. The spectrum of basal skull defects is discussed. Children with midline nasal polyps should have CT or MRI of the skull base prior to surgery to prevent inadvertent hypophysectomy.

Adult↗
PubMed1998

Role of chest CT scanning in the management of patients presenting with head and neck cancer.

BACKGROUND: The detection of synchronous tumors, whether they be second primaries or distant metastases, in patients with head and neck carcinoma drastically affects prognosis and may alter management. Computerized tomographic (CT) scanning of the chest is an effective screening investigation in this group of patients, both in the detection of synchronous second primary tumors, the incidence of which in this study is 15%, and for accurate staging of metastatic pulmonary disease. The incidence of synchronous tumors in patients who are initially seen with head and neck squamous cell carcinoma (HNSCC) has been reported in large retrospective studies as being between 1% and 3%. These may be either second primary tumors or metastases, and the lung is the commonest site for both. METHODS: Eighty-one head and neck cancer patients (67 primary and 14 secondary referrals) treated at the Royal Liverpool University Hospital between 1994 and 1996 underwent CT scanning of the chest with ultrasound of the liver as part of their routine staging. The results were compared with standard chest x-rays also performed in each patient. RESULTS: Fourteen patients had pulmonary tumors detected on the chest CT scan. In 67 patients, the scan was negative. Patients with negative scans tended not to have neck node metastases (64%), whereas patients with positive scans were much more likely to have neck node metastases with negative necks present in only 36% of patients. Where multivariate analysis was carried out, there was a correlation between neck node metastases and positive CT scans of the chest (estimate = 0.5755, standard error = 0.3066, chi2(1) = 6.73, p .047). The sensitivity of chest x-ray compared with CT scan was only 21 % and the specificity 99%. The positive predictive value of a chest x-ray was 75% and the negative predictive value 86%. Intra-abdominal lesions were detected in two patients, one in the liver and one in the adrenal gland. In the latter patient, this was an isolated lesion, but in the former, the chest scan was also positive. In the 67 patients, who were initially seen at the Royal Liverpool Hospital (primary referrals), the incidence of synchronous tumors was 15%. CONCLUSIONS: Synchronous tumors, whether they be second primary tumors or distant metastases, are more common in patients initially seen with head and neck cancer than is realized, their incidence being significantly higher in those patients with cervical metastases. Computerized tomographic scanning of the chest is a more effective screening investigation than chest x-ray in this group of patients and is now used routinely in our department prior to undertaking major head and neck surgery.

Adult↗
PubMed1998

Obesity in Latin American women and children.

National surveys conducted since 1982 were used to assess maternal and child obesity in Latin American and Caribbean countries and in U. S. residents of Mexican descent. Obesity in women, a body mass index (BMI) >/=30 kg/m2, was 3% in Haiti, 8-10% in eight Latin American countries and 29% in Mexican Americans. Median BMI for Latin American women were near or above the 50th percentile of the general U.S. population; values exceeded the 75th percentile in the case of Mexican Americans. The prevalence of overweight (>1 SD above mean weight-for-height) in children 1-5 y of age ranged from 6% in Haiti to 24% in Peru among 13 countries. Overweight occurred in 24% of Mexican-American children. Prevalences of overweight in children and of obesity in women were greater in urban areas and in households of higher socioeconomic status. Overweight in children increased with higher maternal education; however, in some countries, obesity in women decreased with higher education. No general pattern of change over time was observed in eight countries in overweight in children. Obesity in women increased in the three countries with such data and in Mexican-American women and children. There was a tendency for greater national incomes to be associated with greater obesity levels in women and with lower levels of stunting in children. Levels of obesity in the region indicate a public health concern, particularly among women, considering that studies have identified mortality and morbidity risks associated with obesity in adults.

Adult↗
PubMed1997

Abdominal wall endometriosis after amniocentesis. A case report.

BACKGROUND: Amniocentesis is a procedure performed commonly in the evaluation and early diagnosis of fetal chromosomal abnormalities. The procedure is safe, with a major complication rate of 0.5% and the most common minor complication, spotting. CASE: A 27-year-old woman underwent amniocenteses to document pulmonary maturity prior to cesarean section. She presented 18 months later with a 6-month history of left abdominal wall pain and a mass that enlarged 2 days prior to menses and shrank 1 week after. The mass was located at the prior amniocentesis site. Excisional biopsy revealed endometriosis on final pathology. CONCLUSION: To our knowledge, this is the first well-documented case of abdominal wall endometriosis following third-trimester amniocentesis. The procedure should be considered a possible complication of amniocentesis.

Abdominal Muscles↗
PubMed1995

Heparan sulfate stimulates extracellular matrix protein synthesis by mesangial cells in culture.

Heparan sulfate, a glycosaminoglycan which is a component of the glomerular basement membrane and the mesangial matrix, has been demonstrated to inhibit mesangial cell growth. The present studies investigated the effects of heparan sulfate on extracellular matrix protein synthesis by cultured rat mesangial cells. Mesangial cells were metabolically labeled with 35S-methionine and specific extracellular matrix proteins were immunoprecipitated from supernatant and cellular fractions. The following extracellular proteins were assayed: type I collagen, type IV collagen, type V collagen, laminin and fibronectin. Western blotting was performed to demonstrate the specificity of the immunoprecipitates. Heparan sulfate decreased cell number by 23.5%, p < 0.05, while chondroitin sulfate, another glycosaminoglycan, increased cell number by 11.5%, p < 0.05. Heparan sulfate significantly increased type V collagen and laminin in the cellular material and significantly increased laminin and fibronectin in the supernatant material. Chondroitin sulfate had no effect on matrix protein synthesis. Thus, heparan sulfate has effects on both mesangial cell growth and synthesis of matrix proteins and alterations in heparan sulfate may play a role in the development of glomerulosclerosis.

Animals↗
PubMed1995

Insulin-like growth factor-1 stimulates production of mesangial cell matrix components.

Diabetic nephropathy is characterized by mesangial cell proliferation and expansion of the mesangial matrix. Insulin-like growth factor-1 (IGF-1) increases in the kidney early in experimental diabetes. The effect of IGF-1 on mesangial cell proliferation and synthesis of extracellular matrix (ECM) proteins was examined to test the hypothesis that IGF-1 stimulates mesangial cells to synthesize ECM proteins. ECM proteins were measured by immunoprecipitation after metabolic labeling of rat mesangial cells in culture. IGF-1 caused a 2.4-fold increase in mesangial cell proliferation as measured by 3H-thymidine incorporation. IGF-1 caused an increase in cellular laminin, fibronectin and type IV collagen, 46.8 +/- 15.4%, 31.3 +/- 11.4%, and 27.7 +/- 12.6% increase respectively compared to control cells. IGF-1 did not effect cellular type 1 collagen, decrease of 8.2 +/- 8.7%. There was a trend toward increased total protein synthesis by IGF-1, 36.5 +/- 2.5%. In summary, IGF-1 stimulates ECM component production by mesangial cells. Thus, IGF-1 has the capacity to mediate the histologic changes characteristic of diabetic nephropathy.

Animals↗
PubMed1994

(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: I. In vitro characterization.

A diversity of nicotinic acetylcholine receptor (nAChR) subtypes has been identified in mammalian brain using recombinant DNA technology. Alterations in the activity of these acetylcholinegated ion channels have been implicated in a number of central nervous system disorders including Alzheimer's disease (AD). The potential therapeutic usefulness of (-)-nicotine [(S)-3-(1-methyl-2-pyrrolidinyl) pyridine], the prototypic agonist at nAChRs, is severely limited by side effects that are the result of activation of both cholinergic and noncholinergic pathways in the central and peripheral nervous systems. This study sought to determine the in vitro selectivity of (S)-3-methyl-5-(1methyl-2-pyrrolidinyl)isoxazole (ABT 418), a novel analog of (-)-nicotine in which the pyridine ring was replaced with an isoxazole bioisotere, to activate nAChRs. ABT 418 was a potent inhibitor of [3H]-cytisine binding to nAChR in rat brain (Ki = 3 nM) but was inactive (Ki > 10,000 nM) in 37 other receptor/neurotransmitter-uptake/enzyme/transduction system binding assays, including those for alpha-bungarotoxin, muscarinic and 5-hydroxytryptamine3 receptors. In PC12 cells, patch-clamp studies indicated that ABT 418 was an agonist with an EC50 value of 209 microM, a potency to activate cholinergic channel currents some 4-fold less than that of (-)-nicotine (52 microM). Channel current responses elicited by ABT 418 were prevented by the cholinergic channel blocker, mecamylamine. ABT 418 was also approximately 10-fold less potent (EC50 value = 380 nM) than (-)-nicotine (40 nM) in increasing [3H]-dopamine release from rat striatal slices, an effect that was blocked by the nAChR antagonist, dihydro-beta-erythroidine (10 microM).2+ In contrast, ABT 418 appeared equipotent with (-)-nicotine in enhancing 86Rb+ flux from mouse thalamic synaptosomes. ABT 418 demonstrated an in vitro pharmacological profile of cholinergic channel activation that was robust at some nAChR, but not others. The reasons for this are unclear. However, a nAChR subtype selectivity may account for the in vitro potency differences of ABT 418 on various neurotransmitter systems, and the substantial separation between the cognitive enhancement/anxiolytic benefits, and the reduced central nervous system side-effect liabilities seen in vivo. ABT 418 represents the first neuronal nAChR ligand that differentiates the toxicities/liabilities and other negative aspects normally associated with liabilities and other negative aspects normally associated with (-)-nicotine from the potential pharmacological benefits of selective cholinergic channel activation.

Alkaloids↗
PubMed1993

Production of an inhibitor of rat mesangial cell growth by the glomerulus and its alteration in puromycin nephrosis.

Mesangial cell proliferation is found in many forms of progressive renal disease. This proliferation may be due to dysregulation of mesangial cell growth. The studies presented here test the hypothesis that the normal glomerulus produces a regulator of mesangial cell growth. Conditioned media (CM) from primary glomerular cultures were able to inhibit rat mesangial cell growth in a dose- and time-dependent fashion, from 30.0 +/- 3.8 to 86.6 +/- 3.9% growth inhibition. The growth inhibitor in glomerular CM appears to have a molecular weight of less than 3,000. Glomerular CM caused significantly more growth inhibition than did 3T3 fibroblast CM, 77.9 +/- 2.8% growth inhibition by 10% glomerular CM versus 21.2 +/- 5.4% by 10% 3T3 CM (P < 0.001). The growth inhibition was completely reversible. Glomerular CM had no effect on the growth of 3T3 fibroblasts. Treatment of the glomerular CM with either trypsin or neutral protease had no effect on its growth inhibitory activity. Glomerular CM obtained from rats with puromycin aminonucleoside nephrosis caused significantly less growth inhibition than did control glomerular CM; at a concentration of 10% CM, control glomerular CM had 65.1 +/- 1.9% growth inhibition and puromycin had 45.4 +/- 2.1% (P < 0.001). Thus, the rat glomerulus produces a small, nonprotein inhibitor of rat mesangial cell growth and the activity of this inhibitor is reduced in puromycin nephrosis. Impairment of mesangial cell growth regulation may be important in the pathogenesis of progressive renal disease.

3T3 Cells↗
PubMed1992

Evidence that nitric oxide mediates the cyclic GMP response to synaptic activity in the rat superior cervical ganglion.

Preganglionic nerve stimulation in the rat superior cervical ganglion (SCG) caused an increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) in a Ca(2+)-dependent manner. This increase was inhibited by oxyhaemoglobin, and blocked stereoselectively by an inhibitor of nitric oxide synthase, NG-nitro-L-arginine. Thus, nitric oxide or a similar substance appears to mediate the neuronal cyclic GMP response to synaptic activity in the rat SCG.

Animals↗
PubMed1986

Interglomerular heterogeneity of filtration fraction among superficial nephrons: fact or artifact.

The variance (S2inter-G) in protein concentration (CE) of plasma samples collected by micropuncture from randomly chosen surface efferent arterioles was compared to the variance (S2intra-G) of samples collected and re-collected from the same efferent arterioles in 23 Munich-Wistar rats. During efferent arteriolar blood collection, an oil droplet was maintained with gentle suction downstream to the collection pipette to avoid disturbance of natural glomerular blood outflow. S2inter-G averaged 0.067 +/- 0.014 (SE), a value comparable to mean S2intra-G (0.075 +/- 0.016, P greater than 0.50), indicating that the degree of interglomerular heterogeneity in the value of filtration fraction is too small to detect with this micropuncture technique. When ten additional samples were collected using uncontrolled suction pressure, S2inter-G averaged 1.15 +/- 1.30, a value markedly greater than that obtained with controlled pressure. In six nephrons which possessed both glomeruli and efferent arterioles on the surface of the kidney, glomerular capillary pressure (PGC) was monitored during efferent arteriolar blood collection. Applying widely varied suction pressure, PGC changed as much as 42 mmHg, suggesting that improper suction pressure can alter glomerular pressures and flows, hence filtration fraction and CE. Thus, unlike renal proximal tubules, some of the rat renal efferent arterioles do not function as Starling resistors, which may, in turn, account for the wide variability in CE values reported recently by some investigators.

Animals↗
PubMed1984

Physiologic basis for the maintenance of glomerulotubular balance in young growing rats.

To examine the physiologic basis of preservation of glomerulotubular balance in young growing animals, we measured the various determinants for fluid transfer across the glomerular and postglomerular capillaries in young (approximately 40 days, N = 8) and adult (N = 8) male Munich-Wistar rats under mild volume expansion. The single nephron (SN) GFR increased by approximately 2.5-fold from young to adult animals. The increase in SNGFR was due to marked rises in both glomerular plasma flow rate (QA) and ultrafiltration coefficient (Kf). The increase in QA was associated with a nearly 60% reduction in afferent and efferent arteriolar resistances. As with SNGFR, the absolute proximal reabsorption rate (APR) increased by some 2.5-fold, indicating preservation of perfect glomerulotubular balance. Of the factors determining peritubular capillary uptake of APR, the mean oncotic pressure difference across the peritubular capillary was similar in young and adult animals. The mean hydraulic pressure difference was also comparable in the two groups. By contrast, the peritubular capillary reabsorption coefficient (Kr) rose markedly and accounted entirely for the increase in peritubular capillary uptake of APR during growth. These results obtained under mild volume expansion indicate that the maintenance of glomerulotubular balance in the growing rat requires harmonious growth of renal microcirculation, that is, glomerular capillary (Kf) and arteriolar (QA) maturation balances the development of peritubular capillary (Kr).

Absorption↗
PubMed1983

Blood flow dependence of postglomerular fluid transfer and glomerulotubular balance.

The rate of blood flow entering a capillary network can, in some vascular systems, regulate capillary surface area and the rate of fluid and solute transfer. To determine whether such a mechanism exists in the renal peritubular capillary, we performed micropuncture studies in 28 rats during relatively low and high efferent arteriolar blood flow (EABF). High EABF was achieved by intravenous infusion of isoncotic plasma (group 1: from 120 +/- 11 to 301 +/- 49 nl/min [+/- SE]); whole blood with high hematocrit (approximately 75 vol %) (group 2: from 141 +/- 14 to 252 +/- 31 nl/min); or acetylcholine (group 3: from 193 +/- 20 to 266 +/- 26 nl/min). In group 1 rats, plasma infusion caused an increase in single nephron glomerular filtration rate (SNGFR), on average, from 23.2 +/- 2.4 to 45.2 +/- 3.9 nl/min, owing primarily to increased glomerular plasma flow rate (from 63 +/- 5 to 210 +/- 21 nl/min). The rate of fluid uptake by the peritubular capillary, assessed by the absolute rate of proximal fluid reabsorption (APR), also rose significantly, on average from 10.5 +/- 1.2 to 17.5 +/- 2.4 nl/min. This rise in APR was associated with near constancy in mean transcapillary hydraulic (delta Pc) and oncotic (delta IIc) pressure differences, and was therefore attributed to a significant increase in peritubular capillary reabsorption coefficient (Kr), with the mean from 0.017 +/- 0.003 to 0.030 +/- 0.005 nl/(s . mmHg). In group 2 rats, high hematocrit blood infusion led to a significant rise in APR; on average, from 10.7 +/- 0.7 to 15.0 +/- 1.2 nl/min, without changing SNGFR. This rise in APR occurred despite unfavorable changes in the physical forces, namely a significant increase in delta Pc and constancy in delta IIc. Instead, an increase in EABF was again associated with a significant rise in Kr (on average, from 0.016 +/- 0.002 to 0.030 +/- 0.06 nl/[s . mmHg]), which accounted entirely for the rise in APR, independently of SNGFR. In group 3 rats, in which an increase of EABF was induced pharmacologically with acetylcholine, a rise in EABF was also accompanied by a significant increase in Kr, on average, from 0.019 +/- 0.002 to 0.026 +/- 0.004 nl/(s . mmHg). The results indicate that: (a) Kr is modulated by EABF. (b) In view of plasma flow dependence of GFR, blood flow dependence of Kr and APR provides an important basis for glomerulotubular balance.

Absorption↗
PubMed1979

Utilization of prepaid dental health care by students in health professional schools.

Utilization of prepaid dental health care was studied, involving health professional students in an open panel program at the University of Alabama Medical Center. Major barriers to treatment were eliminated and optimal conditions for utilization established. Annual utilization ranged from 44-61 per cent during the period extending from 1969-70 to 1975-76. The majority of enrollees treated sought care from the Student Dental Health Plan (SDHP) clinic, rather than from private practitioners. Thirteen per cent of recent graduates presented for treatment at least once each year during their tenure as students, 57 per cent sought care in more than one year, and 24 per cent did not seek care at all. It was concluded that factors other than cost, accessibility, and educational level operate to prevent total utilization of prepaid dental health care in a young adult age group.

Alabama↗