Biomedical subjects

S A Thomas

Publications and source records attributed to S A Thomas.

At least 19 recordsLinked to original sources

PubMed1995

Pet ownership, social support, and one-year survival after acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial (CAST).

Social support and pet ownership, a nonhuman form of social support, have both been associated with increased coronary artery disease survival. The independent effects of pet ownership, social support, disease severity, and other psychosocial factors on 1-year survival after acute myocardial infarction are examined prospectively. The Cardiac Arrhythmia Suppression Trial provided physiologic data on a group of post-myocardial infarction patients with asymptomatic ventricular arrhythmias. An ancillary study provided psychosocial data, including pet ownership, social support, recent life events, future life events, anxiety, depression, coronary prone behavior, and expression of anger. Subjects (n = 424) were randomly selected from patients attending participating Cardiac Arrhythmia Suppression Trial sites and completed baseline psychosocial questionnaires. One year survival data were obtained from 369 patients (87%), of whom 112 (30.4%) owned pets and 20 (5.4%) died. Logistic regression indicates that high social support (p < 0.068) and owning a pet (p = 0.085) tend to predict survival independent of physiologic severity and demographic and other psychosocial factors. Dog owners (n = 87, 1 died) are significantly less likely to die within 1 year than those who did not own dogs (n = 282, 19 died; p < 0.05); amount of social support is also an independent predictor of survival (p = 0.065). Both pet ownership and social support are significant predictors of survival, independent of the effects of the other psychosocial factors and physiologic status. These data confirm and extend previous findings relating pet ownership and social support to survival among patients with coronary artery disease.

Adult↗

PubMed1995

Antitumor activity of 9(R)-dihydrotaxane analogs.

A novel reduced taxane, 13-acetyl-9(R)-dihydrobaccatin III (1) has been isolated from Taxus canadensis. The selective C-13 deacetylation of this isolate has allowed for the preparation of a wide variety of 9(R)-dihydrotaxane analogs. In general, this series has shown greater stability and water solubility than the 9-carbonyl series while retaining antimicrotubule and tumor cell cytotoxicity activities relative to taxol. Placement of polar functionalities at the C-7 position results in loss of activity whereas alkylation or acylation of either C-7 or C-9 hydroxyl groups ameliorate the activity.

Animals↗

PubMed1995

Noradrenaline is essential for mouse fetal development.

Catecholamines such as noradrenaline and adrenaline have been implicated in numerous physiological processes but, although catecholamine synthesis begins at mid-gestation, previous studies have provided little evidence for any role in early development. Furthermore, there are several case reports of humans with noradrenaline deficiency. To investigate this, we use gene targeting to produce mice lacking dopamine beta-hydroxylase and therefore unable to synthesize noradrenaline or adrenaline. We report here that in heterozygous mothers, most homozygous embryos died in utero, and only about 5% reached adulthood. Survival probably depends on catecholamine transfer across the placenta because, in homozygous mothers, all embryos die in utero. Mortality was due to lack of noradrenaline in utero because it could be prevented by treatment with dihydroxyphenylserine, a precursor that can be converted to noradrenaline in the absence of dopamine beta-hydroxylase. Mutant embryos had a histological phenotype similar to that of embryos deficient in tyrosine hydroxylase, suggesting that death might be due to cardiovascular failure.

Animals↗

PubMed1995

Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice.

The murine Ca(2+)-stimulated adenylyl cyclase (type I) (EC 4.6.1.1), which is expressed predominantly in brain, was inactivated by targeted mutagenesis. Ca(2+)-stimulated adenylyl cyclase activity was reduced 40-60% in the hippocampus, neocortex, and cerebellum. Long-term potentiation in the CA1 region of the hippocampus from mutants was perturbed relative to controls. Both the initial slope and maximum extent of changes in synaptic response were reduced. Although mutant mice learned to find a hidden platform in the Morris water task normally, they did not display a preference for the region where the platform had been when it was removed. These results indicate that disruption of the gene for the type I adenylyl cyclase produces changes in behavior and that the cAMP signal transduction pathway may play an important role in synaptic plasticity.

Adenylyl Cyclases↗

PubMed1995

Rehabilitation teams decisions on discharge housing for stroke patients.

For older people who have had a stroke, appropriate housing can promote independence and well being. However, suboptimal team accommodation recommendations may result in placement of an individual where their needs are not met, and their skills are not maximized. Although clinical judgments regarding patient discharge are routinely made by rehabilitation teams, this area has received limited research attention. This study examines how rehabilitation teams determine the most appropriate housing to recommend to stroke patients after their discharge from hospitals. A Social Judgment Theory approach was used to document and analyze the accommodation recommendations and policies of 13 rehabilitation teams (clinician n = 74). Teams were asked to consider 50 hypothetical stroke patients, and determine the most appropriate discharge housing to recommend to these patients. Each stroke patient was described in terms of 8 attributes: mobility status, ability to manage their own affairs, patient's choice of housing, personal activity of daily living (ADL) skills, domestic and community ADL skills, general health status, social situation, and premorbid living arrangements. Clinicians were provided with a response scale on which to record their recommendations. The results showed considerable yet reliable differences among teams concerning recommendations made, and judgment policies adopted. Although the highly structured and hypothetical nature of this research limits the external validity of findings, the results suggest that teams may also face difficulties with housing recommendations in the more complex clinical environment. Further studies to assess actual clinical team decision making are needed. Such studies could lead to the development of a standardized research-based protocol to help teams formalize and optimize their housing recommendations.

Aged↗

PubMed1995

Changes related to care delivery patterns.

Nurse administrators, faced with a need to increase productivity and reduce costs in response to lower inpatient volumes and increased competition, are restructuring systems of care delivery. A survey of acute care hospitals was conducted to determine the extent of changes in nursing care delivery models, skill mix, assignment of non-nursing personnel to the nursing department, use of unlicensed assistive personnel, and registered nurse role changes in healthcare delivery systems employing unlicensed personnel.

California↗

PubMed1995

Risk factors for stress fractures in female track-and-field athletes: a retrospective analysis.

The incidence and nature of stress fractures and the relationship of potential risk factors to stress-fracture history were investigated retrospectively in a group of 53 female competitive track-and-field athletes. Forty-five stress fractures, diagnosed by clinical findings and bone scan, radiograph, or CT scan, were reported in 22 women. Tibial fractures were the most common (33%). There was no significant difference in bone mineral density at the lumbar spine and tibia/fibula or in percentage body fat and total lean mass when comparing the groups with and without a stress-fracture history. Athletes with a past stress fracture were significantly older at menarche and were more likely to have experienced a history of menstrual disturbance (p < 0.05). Analysis of dietary behavior found that athletes with stress fractures scored significantly higher on the EAT-40 test and were more likely to engage in restrictive eating patterns and dieting. Multiple logistic regression showed that athletes with a history of oligomenorrhea were six times more likely to have sustained a stress fracture in the past, while those who were careful about their weight were eight times more likely. Prevention and treatment of stress fractures in female athletes should include a thorough assessment of menstrual characteristics and dietary patterns.

Adipose Tissue↗

PubMed1994

Synthesis and biological evaluation of C-3'-modified analogs of 9(R)-dihydrotaxol.

Taxol (1) is considered a most exciting new drug in cancer chemotherapy. The promising antitumor activity of 9(R)-dihydrotaxol (3) encouraged us to further explore the structure-activity relationship of this new member of the taxane family. Studies indicated that the C-13 side chain of taxol is indispensable for antitumor activity and that the natural substitution pattern of a 2'(R)-hydroxy and a 3'(S)-acylamino group might be optimal. However, relatively little is known about the effects of the 3'-phenyl ring on activity. The synthesis and biological evaluation of analogs of 3 modified at the C-3' position are described. This study revealed that the 3'-phenyl ring was not required for activity and identified several compounds which had equal or greater in vitro and in vivo activity than taxol.

Animals↗

PubMed1992

Cardiovascular responses of patients with cardiac disease to talking and exercise stress testing.

The blood pressure (BP), heart rate (HR), and premature ventricular contraction responses of patients with cardiac disease during talking were compared with those during exercise stress testing (EST). BPs, HR, and heart rhythm were recorded in 52 patients with cardiac disease before and during talking about an intentionally neutral topic and compared with changes during EST. The systolic and diastolic BP and HR increased significantly during talking. Diastolic BP increased significantly more during talking than during EST stages 1 and 2. The increase in diastolic BP during EST stage 3 did not differ from the increase during talking. HR and systolic BP increased more during EST than during talking. Nine patients had premature ventricular contractions during both EST and talking, two during EST only, and one while talking only. The verbalization protocol provides information about changes in diastolic BP that are not seen with EST. It also may be of value for evaluating heart rhythm, HR, and systolic BP changes for patients whose disabilities preclude EST.

Adult↗

PubMed1991

New 1-(heterocyclylalkyl)-4-(propionanilido)-4-piperidinyl methyl ester and methylene methyl ether analgesics.

A series of new 1-(heterocyclyalkyl)-4-(propionanilido)-4-piperidinyl methyl esters and methylene methyl ethers have been synthesized and pharmacologically evaluated. In the mouse hot-plate test, the majority of compounds exhibited an analgesia (ED50 less than 1 mg/kg) superior to that of morphine. These studies revealed a pharmacological accommodation for many more structurally diverse and far bulkier aromatic ring systems than the corresponding components of the arylethyl groups of the prototypic methyl ester (carfentanil, 2) and methylene methyl ether (sufentanil, 3 and alfentanil, 4) 4-propionanilido analgesics. Compound 9A (methyl 1-[2-(1H-pyrazol-1-yl)-ethyl]-4-[(1-oxopropyl)phenylamino]-4- piperidinecarboxylate), which exhibited appreciable mu-opioid receptor affinity, was a more potent and short-acting analgesic, than alfentanil with less respiratory depression in the rat. On the other hand, the phthalimides 57A and 57B, which exhibited negligible affinity for opioid receptors associated with the mediation of nociceptive transmission (i.e., mu-, kappa-, and delta-subtypes), displayed analgesic efficacy in all antinociception tests. In addition, while 57B, compared to clinical opioids, showed a superior recovery of motor coordination after regaining of righting reflex from full anesthetic doses in the rat rotorod test, 57A showed significantly less depression of cardiovascular function at supraanalgesic doses in the isoflurane-anesthetized rat.

Analgesics↗

PubMed1991

A receptor that is highly specific for extracellular ATP in developing chick skeletal muscle in vitro.

1. Extracellular adenosine 5'-triphosphate (ATP) activated an early excitatory conductance followed by a late potassium conductance in developing chick skeletal muscle. A series of ATP analogues were tested for their ability to activate these two conductances. All compounds tested were either agonists for both responses or for neither. Furthermore, the potency of agonists was similar for the two responses. 2. The order of potency for agonists was ATP approximately adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S) approximately 2-methylthio-ATP (2-CH3S-ATP) greater than 2'-deoxy-ATP approximately 3'-deoxy-ATP greater than adenosine 5'-tetraphosphate (ATP-OPO3) approximately adenosine 5'-diphosphate (ADP). Many other ATP analogues were not agonists. 3. Activation of the excitatory response did not require divalent cations. Furthermore, the concentration-response relation of the excitatory response was similar when ATP was applied as the free anion of ATP (ATP4-) or complexed with a divalent cation (M.ATP2-). 4. Three antagonists of the ATP response were characterized. 8-Br-ATP was a weak antagonist, while 2',3'-dialdehyde-ATP and DIDS (4,4'-diisocyanatostilbene-2,2'-disulphonic acid) were potent irreversible inhibitors. The two conductances were equally affected by these antagonists. 5. These results suggest that both ATP responses are activated through the same receptor type, or two very similar receptors.

Adenosine Triphosphate↗

PubMed1991

Long-bone fractures in young children: distinguishing accidental injuries from child abuse.

While testifying in child abuse cases, physicians have been frustrated by the lawyer who asks, "Doctor, how did this injury happen?" The medical records and radiographs of 215 children younger than the age of 3 with fractures evaluated by a pediatric service during a 5-year period were retrospectively reviewed in an attempt to elucidate the mechanism of childhood fractures. Based on these reviews, two clinicians and two pediatric radiologists rated the likelihood that the fracture was either accidental or due to child abuse. Long-bone fractures were strongly associated with abuse. This report focuses on the 39 children with either humeral or femoral fractures. Fourteen children had humerus fractures. Eleven were considered to be the result of child abuse, and 3 the result of accidents. The latter 3 were supracondylar elbow fractures in children who fell from a tricycle, a rocking horse, or downstairs. Humerus fractures other than supracondylar fractures were all found to be due to abuse. There were 25 femur fractures. Nine were found to be from abuse, 14 were found to be from accidents, and 2 could not be rated. Sixty percent of femur fractions in infants younger than 1 year of age were due to abuse. Although it is taught that femur fractures in young children are inflicted unless proven otherwise, in this study it was found that femur fractures often are accidental and that the femur can be fractured when the running child trips and falls.

Accidental Falls↗

PubMed1990

Permeation of both cations and anions through a single class of ATP-activated ion channels in developing chick skeletal muscle.

Micromolar concentrations of extracellular adenosine 5'-triphosphate (ATP) elicit a rapid excitatory response in developing chick skeletal muscle. Excitation is the result of a simultaneous increase in membrane permeability to sodium, potassium, and chloride ions. In the present study we quantify the selectivity of the ATP response, and provide evidence that a single class of ATP-activated ion channels conducts both cations and anions. Experiments were performed on myoballs using the whole-cell patch-clamp technique. We estimated permeability ratios by measuring the shift in reversal potential when one ion was substituted for another. We found that monovalent cations, divalent cations, and monovalent anions all permeate the membrane during the ATP response, and that there was only moderate selectivity between many of these ions. Calcium was the most permeant ion tested. To determine if ATP activates a single class of channels that conducts both cations and anions, or if ATP activates separate classes of cation and anion channels, we analyzed the fluctuations about the mean current induced by ATP. Ionic conditions were arranged so that the reversal potential for cations was +50 mV and the reversal potential for anions was -50 mV. Under these conditions, if ATP activates a single class of channels, ATP should not evoke an increase in noise at the reversal potential of the ATP current. However, if ATP activates separate classes of cation and anion channels, ATP should evoke a significant increase in noise at the reversal potential of the ATP current. At both +40 and -50 mV ATP elicited a clear increase in noise, but at the reversal potential of the ATP current (-5 mV), no increase in noise above background was seen. These results indicate that there is only a single class of excitatory ATP-activated channels, which do not select by charge. Based on analysis of the noise spectrum, the conductance of individual channels is estimated to be 0.2-0.4 pS.

Adenosine Triphosphate↗

PubMed1990

Irreversible desensitization of ATP responses in developing chick skeletal muscle.

1. In developing chick skeletal muscle, extracellular adenosine 5'-triphosphate (ATP) elicits an early excitatory conductance increase followed by a late potassium conductance increase. Both of these responses desensitize profoundly. Intracellular recordings and whole-cell voltage-clamp recordings were made in order to examine the time course and mechanism of desensitization and the recovery from desensitization. 2. Most of the loss of responsiveness to ATP occurred during the first minute of exposure to ATP. For the excitatory conductance, the loss of responsiveness to ATP resulted in part from long-lasting activation of the ATP-sensitive channels and in part from entrance into an inactive (non-conducting) state. In contrast, desensitization of the potassium conductance was entirely the result of a relatively fast transition to an inactive state. 3. Recovery from desensitization took many hours for both responses and was quite sensitive to temperature. 4. Recovery from desensitization for both responses was prevented by preincubation with the glycosylation inhibitor, tunicamycin. Several lines of evidence suggest that tunicamycin treatment blocked the delivery of new ATP receptors to the cell surface. 5. The recovery of the early response to ATP following exposure to two non-competitive inhibitors of the ATP response was also examined. These two compounds are thought to covalently modify the receptor. After exposure to either of these inhibitors, responsiveness to ATP returned over a time course that was similar to the time course of recovery from desensitization. 6. These results indicate that, following activation, ATP receptors do not become available for reactivation, and that recovery from desensitization is due to the insertion of newly synthesized receptors into the plasma membrane.

Action Potentials↗

PubMed1990

Australian workers with back injury: a statistical overview.

This paper reviews international and Australian data concerning the occurrence of back injuries amongst the labour force. Analyses of Australian Bureau of Statistics data for the period 1977 to 1986 revealed substantial differences between Australian states in their rates of back injury claims for work injuries, with a decline in rates over the ten years surveyed. Analyses of WorkCare data from the State of Victoria in Australia revealed that claimants with back injury claims of greater than 12 months standing were very costly. A total of 8,633 claimants accounted for 68.7% of all payments for back injury ($362 million out of a total of $527 million) when these claimants represented only 10.7% of all back injury claimants for the period September 1985 to May 1989. Substantial variations were found in claim rates across occupations and age levels. An almost linear (r = 0.98) association was found between age and proportion of long term claimants at each age level. It is suggested that these data could be used to identify 'at risk' groupings with a view to the implementation of preventive measures.

Adolescent↗

PubMed1989

Spirituality: an essential dimension in the treatment of hypertension.

In this time of "burnout" and high turnover in nursing, we must attend to our own needs for healing. Integration of a spiritual dimension in our lives and work are central to our health. A balanced life allows nurses to give more, not less, to their practice. Spirituality enlarges the purpose and meaning of our lives and work. Nursing practice entails care, comfort, and healing. These nursing actions flow naturally from a peaceful center.

Adult↗

PubMed1989

A calcium- and voltage-dependent chloride current in developing chick skeletal muscle.

1. Depolarization of embryonic chick myotubes from negative potentials elicits a rapid spike followed by a long-duration after-potential. The ionic basis of the long-duration after-potential was examined by making intracellular recordings from cultured myotubes, and by making whole-cell patch-clamp recordings from myoblasts and myoballs. 2. The peak potential of the long-duration after-potential varied with the chloride gradient, suggesting that a conductance increase to chloride is involved in generating the after-potential. However, a calcium current was also implicated, since lowering the extracellular calcium or replacing extracellular calcium with cobalt abolished the after-potential. 3. When extracellular calcium was replaced with strontium or barium, short-duration spikes similar to calcium spikes were observed, but only strontium was able to support activation of long-duration after-potentials. Intracellular injection of calcium or strontium into myotubes bathed in calcium-free extracellular solutions restored the ability of depolarization to evoke an after-potential. Intracellular injection of magnesium, barium, nickel or cobalt did not restore this ability. These experiments strongly suggested that the long-duration after-potential was due to a calcium- and voltage-activated chloride current. 4. Whole-cell voltage-clamp recordings from myoballs and myoblasts showed that a large chloride conductance could be activated by depolarization when the internal free calcium concentration was buffered at levels greater than 10(-7) M. At 2.5 x 10(-7) M-calcium, the voltage dependence of activation was steepest in the range of -30 to -20 mV and the activation kinetics varied with the membrane potential. The time to half-maximal activation ranged from 0.1 s at positive potentials to greater than 1 s at more negative potentials. The time constant for deactivation was approximately 1 s at -50 mV. No inactivation was observed. 5. The selectivity of the chloride current was measured by substituting other anions for chloride. The following permeability series was found: I- greater than NO3- greater than Br- greater than Cl- greater than acetate greater than F- greater than SO4- = glucuronate. Thus anion permeability decreased as the hydration radius increased. 6. Measurements of the resting potential of developing myoblasts and myotubes under 'physiological' conditions (37 degrees C, bicarbonate buffer) suggest that the after-potential acts to depolarize these cells 10-20 mV above their resting potential (approximately -60 mV) for several seconds. 7. We discuss the possibility that the long-duration after-potential may be involved in triggering myoblast fusion and in the generation of bursts of spontaneous contractions in developing myotubes.

Animals↗

PubMed1989

Blood pressure, heart rate, and heart rhythm changes in patients with heart disease during talking.

Blood pressure and heart rate were recorded in 37 patients with cardiac disease while they were resting quietly and talking. Heart rate, systolic blood pressure, and diastolic blood pressure were all significantly greater while the patients were speaking than while they were resting silently. In addition, ventricular and atrial arrhythmias were more frequent while they were talking than while they were quiet. Higher resting systolic blood pressure levels also were associated with larger blood pressure increases while the patients were speaking. Older patients exhibited significantly greater systolic pressure increases while talking than younger patients. Therapeutic doses of antihypertensive medications, including beta-blockers, calcium channel blockers, and diuretics did not block the heart rate and blood pressure increases while the patients were talking. These findings suggest that more attention needs to be paid to the hemodynamic consequences of communication in patients with coronary heart disease. Coupled with previous research findings, these data also suggest that clinicians need to attend to verbal communications during routine diagnostic procedures for evaluating cardiovascular function.

Adult↗