Biomedical subjects

S A Smith

Publications and source records attributed to S A Smith.

At least 109 records · Page 6Linked to original sources

PubMed1999

Ventilatory responses to dynamic exercise elicited by intramuscular sensors.

PURPOSE: Eight subjects, aged 27.0+/-1.6 yr, performed incremental workload cycling to investigate the contribution of skeletal muscle mechano- and metaboreceptors to ventilatory control during dynamic exercise. METHODS: Each subject performed four bouts of exercise: exercise with no intervention (CON); exercise with bilateral thigh cuffs inflated to 90 mm Hg (CUFF); exercise with application of lower-body positive pressure (LBPP) to 45 torr (PP); and exercise with 90 mm Hg thigh cuff inflation and 45 torr LBPP (CUFF+PP). Ventilatory responses and pulmonary gas exchange variables were collected breath-by-breath with concomitant measurement of leg intramuscular pressure. RESULTS: Ventilation (VE) was significantly elevated from CON during PP and CUFF+PP at workloads corresponding to > or = 60% CON peak oxygen uptake (VO2peak) and during CUFF at workloads > or = 80% CON VO2peak, P < 0.05. The VO2 at which ventilatory threshold occurred was significantly reduced from CON (2.17+/-0.28 L x min(-1)) to 1.60+/-0.19 L x min(-1), 1.45+/-0.15 L x min(-1), and 1.15+/-0.11 L x min(-1) during CUFF, PP, and CUFF+PP, respectively. The slope of the linear regression describing the VE/CO2 output relationship was increased from CON by approximately 22% during CUFF, 40% during PP, and 41% during CUFF+PP. CONCLUSIONS: As intramuscular pressure was significantly elevated immediately upon application of LBPP during PP and CUFF+PP without a concomitant increase in VE, it seems unlikely that LBPP-induced increases in VE can be attributed to activation of the mechanoreflex. These findings suggest that LBPP-induced reductions in perfusion pressure and decreases in venous outflow resulting from inflation of bilateral thigh cuffs may generate a metabolite sensitive intramuscular ventilatory stimulus.

Adult↗

PubMed1999

Respiratory failure as a complication of pharyngitis: Lemierre's syndrome.

The emergence of drug-resistant organisms has promoted increased calls for judicious use of antibiotics in cases of pediatric pharyngitis. Although these recommendations are largely justified, the case of a 16-year-old girl with pharyngitis is reported to alert readers to an unusual complication, Lemierre's syndrome. This complication of pharyngitis and its relevance to changing practice habits are discussed.

Adolescent↗

PubMed1999

Natural history of diabetic macular streak exudates: evidence from a screening programme.

BACKGROUND/AIMS: Diabetic retinopathy screening guidelines recommend referral to an ophthalmologist if there is exudate within one disc diameter of the fovea. Many of these patients, however, have resolution of small amounts of exudate without treatment. This study aimed to assess whether patients with minimal streak or dot exudates within one disc diameter of the fovea can be monitored in a screening programme without compromising visual acuity. METHODS: A retrospective review of records and Polaroid photographs obtained by one screening centre over a 10 year period was performed. Outcomes measured were referral rates, alteration of Snellen visual acuity, and the need for macular photocoagulation treatment. RESULTS: 55 patients (74 eyes) fulfilled entry criteria (37 streak and 37 dot exudates). Mean follow up was 56.1 months (range 12-127 months). Twenty five patients (30 eyes) were referred to an ophthalmologist. 13 eyes (17.6%) required macular photocoagulation treatment. Four eyes (5.4%) lost two or more lines of Snellen acuity over the follow up period (three from macular oedema and one from macular ischaemia). There was no relation between the presence or resolution of minimal exudate and visual loss (p>0.2). CONCLUSION: It is appropriate to monitor eyes with streak or dot macular exudates at 6-9 monthly intervals in a screening programme.

Adult↗

PubMed1999

Bilateral Horner's syndrome: detection and occurrence.

OBJECTIVE: To develop a method for the detection of bilateral Horner's syndrome in patients with bilateral interruption of the cervical sympathetic pathway or widespread autonomic neuropathy. METHODS: Darkness pupil diameters and redilatation times during light reflexes have been recorded with infrared TV pupillometry in 65 healthy subjects, 47 patients with unilateral Horner's syndrome, and 20 patients with bilateral Horner's syndrome. The aetiologies of the last group were diabetic autonomic neuropathy (three cases), amyloidosis (four), pure autonomic failure (PAF) (four), dopamine-beta-hydroxylase deficiency (two), and one case each of hereditary sensory and autonomic neuropathy (HSAN) type III, carcinomatous sympathetic neuropathy, familial dysautonomia, multiple system atrophy, Anderson-Fabry disease, and anterior spinal artery thrombosis at C5,6 and one had had bilateral cervical sympathectomies. RESULTS: Darkness diameters on the affected side were below normal in 12 patients with unilateral Horner's syndrome, the measurement yielding only 26% sensitivity for detection of the condition. By contrast, the time taken to reach three quarter recovery in the light reflex (T3/4) was abnormally prolonged (redilatation lag) in 33 of the same eyes. The measurement yielded 70% sensitivity and 95% specificity for detection of the condition. In 20 cases, diagnosed on clinical grounds as having bilateral Horner's syndrome of various aetiologies, pupil diameters were abnormally small on both sides in five and on one side in three patients. Fourteen of these patients had significant redilatation lag in both eyes, five patients in one eye, and one patient had it in neither eye. Measurement of redilatation lag was therefore a more sensitive diagnostic test than pupil diameter in both unilateral and bilateral Horner's syndrome. CONCLUSIONS: Provided that the pupils are not tonic, bilateral Horner's syndrome can be diagnosed on the basis of redilatation lag. It occurs clinically in some generalised autonomic neuropathies and with interruption of the local sympathetic nerve supplies to the two eyes.

Adult↗

PubMed1999

Effects of creatine supplementation on the energy cost of muscle contraction: a 31P-MRS study.

Five women and 3 men (29.8 +/- 1.4 yr) performed dynamic knee-extension exercise inside a magnetic resonance system (means +/- SE). Two trials were performed 7-14 days apart, consisting of a 4- to 5-min exhaustive exercise bout. To determine quadriceps cost of contraction, brief static and dynamic contractions were performed pre- and postexercise. (31)P spectra were used to determine pH and relative concentrations of P(i), phosphocreatine (PCr), and betaATP. Subjects consumed 0.3 g. kg(-1). day(-1) of a placebo (trial 1) or creatine (trial 2) for 5 days before each trial. After creatine supplementation, resting DeltaPCr increased from 40.7 +/- 1.8 to 46. 6 +/- 1.1 mmol/kg (P = 0.04) and PCr during exercise declined from -29.6 +/- 2.4 to -34.1 +/- 2.8 mmol/kg (P = 0.02). Muscle static (DeltaATP/N) and dynamic (DeltaATP/J) costs of contraction were unaffected by creatine supplementation as well as were ATP, P(i), pH, PCr resynthesis rate, and muscle strength and endurance. DeltaATP/J and DeltaATP/N were greatest at the onset of the exercise protocol (P < 0.01). In summary, creatine supplementation increased muscle PCr concentration, which did not affect muscle ATP cost of contraction.

Adenosine Triphosphate↗

PubMed1999

Carotid baroreflex function during prolonged exercise.

The present investigation was designed to uncouple the hemodynamic physiological effects of thermoregulation from the effects of a progressively increasing central command activation during prolonged exercise. Subjects performed two 1-h bouts of leg cycling exercise with 1) no intervention and 2) continuous infusion of a dextran solution to maintain central venous pressure constant at the 10-min pressure. Volume infusion resulted in a significant reduction in the decrement in mean arterial pressure seen in the control exercise bout (6.7 +/- 1.8 vs. 11.6+/- 1.3 mmHg, respectively). However, indexes of central command such as heart rate and ratings of perceived exertion rose to a similar extent during both exercise conditions. In addition, the carotid-cardiac baroreflex stimulus-response relationship, as measured by using the neck pressure-neck suction technique, was reset from rest to 10 min of exercise and was further reset from 10 to 50 min of exercise in both exercise conditions, with the operating point being shifted toward the reflex threshold. We conclude that the progressive resetting of the carotid baroreflex and the shift of the reflex operating point render the carotid-cardiac reflex ineffectual in counteracting the continued decrement in mean arterial pressure that occurs during the prolonged exercise.

Adult↗

PubMed1999

Morphine metabolism in the pregnant guinea pig and her pups.

The study of chronic in utero exposure to heroin and morphine in the human is limited by polysubstance abuse. The guinea pig was used as a model for the human to determine the in vivo and in vitro effect of chronic morphine exposure on morphine metabolism in the pregnant dam and her offspring. In vivo pharmacokinetics of morphine were examined in pregnant guinea pigs following pretreatment with either saline or morphine. In vitro hepatic enzyme kinetics were also examined in a similar group of pregnant dams and their fetuses. Additional pregnant dams were allowed to give birth and their pups' enzyme kinetics were studied at 1, 3, and 7 days. Apparent V(MAX) for the formation of both morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) formation was significantly increased in the morphine-treated pregnant guinea pig. However, no effect of morphine treatment was detectable on the in vivo pharmacokinetics of morphine in the pregnant dam. The apparent morphine K(M) for the formation of M3G was significantly different than the apparent K(M) for the formation of M6G. Significant age effects on the enzyme kinetics were found. The apparent V(MAX) for the formation of both glucuronides increased through the neonatal period. Through literature comparisons, the guinea pig was shown to have in vivo pharmacokinetics similar to the pregnant human, and the guinea pig pups were found to have enzyme development consistent with in vivo pharmacokinetic development seen in human neonates, infants and children.

Animals↗

PubMed1999

Clinical consultations using store-and-forward telemedicine technology.

OBJECTIVE: To investigate the potential role of a store-and-forward (SAF) telemedicine system in specialty consultations initiated by primary care physicians. MATERIALS AND METHODS: In this pilot telemedicine study, patients needing consultations in cardiology, dermatology, endocrinology, and orthopedics had both standard face-to-face (FTF) consultations and SAF consultations. RESULTS: Fifteen patients had both FTF and SAF consultations, 4 had echocardiograms transmitted for an SAF consultation only, and 1 had an SAF consultation but no FTF appointment. Of 19 diagnoses made, all were essentially the same in both types of consultations; 14 of 15 FTF consultations and 15 of 19 SAF consultations resulted in additional treatment recommendations. CONCLUSIONS: While it was possible to develop a desktop system for SAF consultations, the equipment was not adequately integrated. Without total digital input, including electronic patient medical records, packaging of information is laborious and impractical. Seamlessly adapting to existing clinical practice is vital. Issues such as increasing work for the physicians or office staff, gathering adequate patient information, and designing a referral process were more difficult than we had anticipated. Patient acceptance was high, but the clinical pilot had very small numbers.

Female↗

PubMed1999

Cesarean section scar as a cause of abnormal vaginal bleeding: diagnosis by sonohysterography.

A previously undescribed cause of abnormal uterine bleeding is presented. Nine of 310 women evaluated by sonohysterography for abnormal bleeding demonstrated an 8 to 17 mm gap in the anterior lower uterine segment myometrium at the site of prior cesarean deliveries. All women were premenopausal and had a history of 2 to 12 days of postmenstrual spotting. Presumably a lack of coordinated muscular contractions occurs around the cesarean scar, allowing the defect to collect menstrual debris. Subsequently, the debris leaches out through the cervix for several days after the majority of menstrual flow has ceased.

Adult↗

PubMed1999

Tilapia (Oreochromis niloticus) and rodents exhibit similar patterns of inhibited antibody production following exposure to immunotoxic chemicals.

The hemolytic plaque forming cell assay (PFC), a measure of ability to produce specific antibodies following challenge with antigen, is a powerful predictor of immunosuppression in chemical-exposed rodents. The efficacy of this assay for predicting humoral immunosuppression in non-rodent species remains unknown. In the present report, tilapia (Oreochromis niloticus) were exposed to 9 chemical agents known to inhibit antibody production in mice (benzo[a]pyrene, 7,12-dimethylbenzanthracene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, dimethyl nitrosamine, cadmium chloride, azathioprine, hexachlorocyclohexane, T2 mycotoxin and toluene) and 5 chemical agents which do not inhibit this response (oxymethalone, acetonitrile, diethylstilbesterol, t-butylhydroquinone and formaldehyde). Eight of 9 agents which inhibit antibody production in rodents caused decreased PFC responses in fish. All 5 compounds with negative humoral effects in rodents were also negative in fish. Thus, 13/14 chemical agents tested gave similar results in tilapia as reported in rodents, suggesting a comparable pattern of humoral immunosuppression in chemical-exposed tilapia to that seen in laboratory rodent models.

Animals↗

PubMed1998

Fused aminotetralins: novel antagonists with high selectivity for the dopamine D3 receptor.

Starting from a series of 2-aminotetralins 1, a novel series of N-[4-(4-phenylbenzoylamino)butyl]-octahydrobenzoquinolines and hexahydrobenzoindoles with high potency and selectivity for the dopamine D3 receptor has been designed. The effect of ligand chirality on binding affinity has been established. Selected derivatives (e.g. 2o, 2p) show high functional selectivity and enhanced in vivo properties compared to 1.

Animals↗

PubMed1998

Favorable prognostic significance of high-level retinoic acid receptor beta expression in neuroblastoma mediated by effects on cell cycle regulation.

We have previously shown that ectopic overexpression of retinoic acid receptor (RAR) subtypes alpha, beta and gamma in human neuroblastoma cells had different effects on growth and retinoid sensitivity. Only overexpressed RAR beta induced profound growth inhibition in the absence of additional retinoid, and increased retinoid sensitivity. In this study, we measured mRNA expression levels of RAR alpha, beta, and gamma in 50 primary neuroblastoma tumor samples, and found a strong correlation between favorable patient prognosis and high-level RAR beta expression. Human neuroblastoma cells transfected with a vector expressing RAR beta demonstrated irreversible growth arrest following a 1 week exposure to all-transretinoic acid, whereas control cells continued to proliferate. In the absence of additional retinoid, RAR beta transfectants demonstrated a higher proportion of cells in the G0/G1 phase of the cell cycle, increased p21WAF1/CIP1 expression and specific binding to a retinoic acid response element. These were changes which we also observed in control neuroblastoma cells following retinoid treatment. Our data indicate that RAR beta is an important factor mediating the growth inhibitory effects of retinoids in neuroblastoma cells. The favorable effect of high-level RAR beta expression on prognosis in primary tumor tissue may occur through RAR beta effects on p21 expression and consequent G0/G1 cell cycle arrest.

Cell Cycle↗

PubMed1998

Benzo[a]pyrene-induced hypocellularity of the pronephros in tilapia (Oreochromis niloticus) is accompanied by alterations in stromal and parenchymal cells and by enhanced immune cell apoptosis.

Numerous reports indicate that carcinogenic polycyclic aromatic hydrocarbons (PAH) are mammalian immunotoxicants. These environmental contaminants are widely distributed in both freshwater and costal marine ecosystems where they have been found to bioaccumulate in aquatic species, yet limited information exists regarding potential adverse effects of specific PAH on fish immune function. In the present report, Oreochromis niloticus fish (tilapia) were exposed by intraperitoneal injection to 5, 25, or 50 mg/kg of the PAH, benzo[a]pyrene (B[a]P). Histopathologic evaluation of the primary hematopoietic compartment of fish, the pronephros, demonstrated increased vacuolation of both stromal and parenchymal cells, reduction of lymphoid elements, and immune cell apoptosis. Total pronephros cell counts were diminished in a dose-dependent manner by the chemical exposure. The oxidative metabolic burst in phorbol myristate acetate (PMA)-simulated macrophages isolated from the pronephros was significantly inhibited by B[a]P, but only at the highest dose level employed. The phagocytic capacity of pronephros macrophages was not altered by the chemical treatment.

Animals↗

PubMed1998

Effector systems involved in the insulin secretory responses to efaroxan and RX871024 in rat islets of Langerhans.

One component of the mechanism by which imidazoline compounds promote insulin secretion involves closure of ATP-sensitive K+ channels in the beta-cell plasma membrane. Recently, however, it has also been proposed that these compounds may exert important effects on more distal effector systems. In the present work, we have investigated the contribution played by protein kinases A and C to the insulin secretory responses of isolated rat islets of Langerhans treated with efaroxan and RX871024 (1-phenyl-2-(imidazolin-2-yl) benzimidazole). Removal of extracellular Ca2+ or blockade of voltage-sensitive Ca2+ channels prevented stimulation of insulin secretion by efaroxan, confirming a critical role for increased Ca2+ influx in the secretory response. By contrast, inhibition of protein kinases A or C failed to alter efaroxan-induced insulin secretion. RX871024 dose-dependently increased insulin secretion from cultured islets incubated with 20 mM glucose. This effect was unaffected by modulation of protein kinase C, but was significantly attenuated by a selective inhibitor of protein kinase A (Rp-cAMPs). Measurements of cAMP revealed that RX871024 increased the islet cAMP content by more than 3-fold; reaching values similar in magnitude to those elicited by 50 microM 3-isobutyl-1-methyl xanthine. The results reveal that neither protein kinase A nor protein kinase C is obligatory for stimulation of insulin secretion by imidazolines. However, they suggest that a rise in cAMP may contribute to the amplified secretory response observed when cultured islets are incubated with RX871024 in the presence of a stimulatory glucose concentration.

Adrenergic alpha-Antagonists↗

PubMed1998

In vitro effects of the extracellular protein of Renibacterium salmoninarum on phagocyte function in brook trout (Salvelinus fontinalis).

Renibacterium salmoninarum is a facultative intracellular pathogen often found in host phagocytes where it appears to successfully avoid the host fish's immunological defenses. The objective of this investigation was to determine if soluble extracellular protein (ECP) produced by R. salmoninarum may contribute to the immunomodulation in bacterial kidney disease (BKD) via inhibition of phagocyte respiratory burst and/or phagocytosis mechanisms. Splenic cells from adult brook trout (Salvelinus fontinalis) were incubated with two different concentrations of ECP (0.1 mg/ml and 1.0 mg/ml) and viable R. salmoninarum. Splenic cell cultures were evaluated for respiratory burst activity via flow cytometry with the dichlorofluorescin diacetate (DCF-DA) assay and for phagocytosis via light microscopic assessment of microsphere engulfment. Respiratory burst activity was significantly inhibited in all treatment groups as compared to untreated fish, while no differences were noted in phagocytic activity.

Animals↗

PubMed1998

Fine structure of the retinal pigment epithelium of Oreochromis niloticus L. (Cichlidae; Teleostei) in light- and-dark adaptation.

The fine structure of the retinal pigment epithelium (RPE) of the cichlid Oreochromis niloticus was investigated in both light- and dark-adaptation. The eyes of four light-adapted and from four dark-adapted O. niloticus were fixed routinely for light and transmission electron microscopy. The RPE consisted of a single layer of columnar cells showing minimal basal infolding but plentiful apical processes that in light-adaptation interdigitated with the photoreceptor outer segments. The epithelial cells were joined by a series of basally-located tight junctions. These cells showed a large vesicular nucleus, plentiful smooth endoplasmic reticulum and polysomes, but only small amounts of rough endoplasmic reticulum. Phagosomes, lysosome-like bodies, lipid droplets, and myeloid bodies were observed. The choriocapillaris was a single layer of large-caliber capillaries, and Bruch's membrane (complexus basalis) was a trilaminate structure typical of teleosts. The RPE melanosomes moved basally (sclerally) in dark-adaptation and apically (vitreally) during light-adaptation. Other morphological features which changed at least to some degree during retinomotor responses were: the location of the RPE nucleus; the location and electron density of the mitochondria; and the location, number, and size of the myeloid bodies. A number of unique morphological changes take place within the RPE cells of this species during the circadian cycle in addition to the movement of melanosomes characterized in other vertebrates.

Adaptation, Ocular↗

PubMed1998

Photoreceptor fine structure in Oreochromis niloticus L. (Cichlidae; Teleostei) in light- and dark-adaptation.

The structure and arrangement of both light- and dark-adapted retinal photoreceptors of Oreochromis niloticus L. were studied. Eyes of four light-adapted and four dark-adapted O. niloticus were fixed routinely for light and transmission electron microscopy. Rods, single cones, and double (twin) cones were present in a ratio of 30:1:2, respectively. Light-adapted rods were tall, extending into the retinal epithelial layer. Rod inner segments showed a distal ellipsoid of mitochondria that narrowed dramatically in the myoid region. Dark-adapted rod inner segments were much shorter with a thicker myoid region, indicating photomechanical movement. Rod synaptic spherules were small, with both superficial synapses and invaginated sites. Single cones were similar to individual members of a double cone. Cone outer segments consisted of uniform discs with a single incisure. All cones displayed a short, tapering outer segment, a large ellipsoid of mitochondria, and a myoid region rich in organelles. Both members of double cones had extensive subsurface cisternae along their contiguous surfaces. Cone inner segments changed little throughout the circadian cycle, suggesting an absence of significant retinomotor movements. Large, vesicular cone nuclei were located adjacent to or through the external limiting membrane. The cones' synaptic pedicles had larger synapses than rod spherules, with more of both invaginated (ribbon) and conventional (superficial) synaptic sites. Cone photoreceptors were arranged in a repeating square mosaic pattern with a single cone surrounded by four double (twin) cones. The photoreceptors of the Nile tilapia presented basic piscine characteristics, and also some more species-specific features.

Adaptation, Ocular↗

PubMed1998

Unilateral enucleation of adult rats does not effect the synapse-to-neuron ratio within the stratum griseum superficiale of the superior colliculi.

Ninety-day-old hooded male rats were anaesthetised with an intraperitoneal injection of a mixture of xylazine and ketamine and had their right eyes removed. Groups of non-enucleated control and enucleated rats were killed at either 150 or 390 days of age by intracardiac perfusion with fixatives. Stereological methods were used to estimate the synapse-to-neuron ratios within the stratum griseum superficiale (SGS) layers of both the ipsi- and contra-lateral superior colliculi. The enucleation had no significant effects on this ratio irrespective of the side or age of the brains examined. This experiment shows that a constant synapse-to-neuron ratio may be maintained within the SGS layer of the rat superior colliculus despite the inevitable loss of synaptic contacts due to the anterograde transneuronal degeneration initiated by the enucleation.

Animals↗