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Biomedical subjects

D H Smith

Publications and source records attributed to D H Smith.

At least 181 records · Page 10Linked to original sources
PubMed1991

A comparative study of atenolol, nifedipine and their combination in the treatment of hypertension.

The antihypertensive effects, as assessed by clinical and ambulatory blood pressure measurement, of nifedipine slow-release (SR), atenolol and the two in combination were evaluated in 28 known hypertensives in a placebo-controlled, double-blind, randomised cross-over trial. Clinical blood pressure was significantly lower on combination therapy (P less than 0.025) than on either agent alone, although all therapeutic agents reduced blood pressure significantly when compared with placebo (P less than 0.01). All ambulatory blood pressure measurements obtained on any therapeutic agent were significantly lower than those obtained on placebo (P less than 0.01). The mean daytime (08h00-17h00) ambulatory blood pressure measurement as well as the percentage of this monitoring period during which patients were hypertensive were significantly lower (P less than 0.01) on combination therapy than on nifedipine SR. A similar pattern was observed for 24-hour ambulatory blood pressure measurements. Headache was the most significant adverse effect. This was most common with nifedipine SR, less common with combination therapy and least common with atenolol. Combination therapy with nifedipine SR and atenolol is therefore a viable therapeutic alternative in the treatment of patients with benign essential hypertension.

Adult↗
PubMed1991

Response of 7- to 15-month-old infants to sequential immunization with Haemophilus influenzae type b-CRM197 conjugate and polysaccharide vaccines.

OBJECTIVE: To evaluate the immunologic potential of infants 7 to 15 months of age to respond to Haemophilus influenzae type b polysaccharide vaccine following immunization with H influenzae b oligosaccharide-CRM197 conjugate vaccine. STUDY DESIGN: One hundred seventy-one infants, aged 7 to 15 months, were consecutively and alternatively assigned to one of three immunization protocols. Group 1 (n = 71) received three doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine, group 2 (n = 47) received two doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine followed by one dose of H influenzae type b polysaccharide vaccine, and group 3 received one dose of H influenzae b oligosaccharide-CRM197 conjugate vaccine followed by two doses of H influenzae type b polysaccharide vaccine. Immunizations were given on day 0 and at 2 months and 6 months. Anti-H influenzae type b polysaccharide antibody levels were measured on day 0 and 2, 3, 6, 7, and 12 months after the study began. RESULTS: Haemophilus influenzae type b polysaccharide vaccine given as a second dose stimulated an antibody rise but did so less effectively than H influenzae b oligosaccharide-CRM197 conjugate vaccine. Two doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine were highly immunogenic; geometric means were 31 and 35 micrograms/mL in the 7- to 11-month and 12- to 15-month age groups, respectively. Following two doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine, both immunization protocols resulted in (1) equally high geometric mean antibody levels 1 month after immunization and (2) similar geometric mean antibody levels 6 months after immunization. CONCLUSIONS: Haemophilus influenzae b oligosaccharide-CRM197 conjugate vaccine induces antibody levels that would be expected to protect infants from initial invasion and primes the immune system for an anamnestic response. Our data indicate that if a booster immunization is needed, H influenzae type b polysaccharide vaccine could be an alternative to H influenzae b oligosaccharide-CRM197 conjugate vaccine.

Antibodies, Bacterial↗
PubMed1991

Effects of angiotensin II on pressor responses to norepinephrine in humans.

In previous studies in the conscious rabbit and in isolated artery preparations, low doses of angiotensin II synergistically amplified the pressor effects of the sympathetic neurotransmitter, norepinephrine (NE). To determine whether these observations could be replicated in humans, 9 normal adult male volunteers (mean age: 34) each were given 3 i.v. doses of NE (25, 50 and 100 micrograms.kg-1.min-1) during consecutive 10 min infusion periods. On a second study day, the procedure was repeated during infusion of angiotensin II in a subpressor dose (1.25 ng.kg-1.min-1). The angiotensin II didn't alter the BP responses to NE, but it attenuated the heart rate (HR) decreases associated with the NE infusions by 80% (P less than 0.05), 42% (P less than 0.05) and 42% (P less than 0.1). The two study days were then repeated following 2 weeks of oral treatment with the angiotensin converting enzyme inhibitor captopril (which, despite significantly decreasing baseline BP, also tended to decrease HR). In the presence of captopril, the pressor responses to the NE challenges were reduced by 50% (P less than 0.05), 33% (P less than 0.05) and 13% (P less than 0.1) compared with the pre-captopril responses. Thus, angiotensin II in subpressor doses appears to enhance NE pressor effects by attenuating the compensatory HR responses, whereas inhibition of endogenous angiotensin II mechanisms weakens the BP-raising actions of NE. These findings in humans are consistent with earlier observations that the renin-angiotensin system can directly amplify sympathetic pressor effects in two separate ways: by modifying baroreceptor sensitivity and by enhancing the actions of norepinephrine on vascular smooth muscle.

Administration, Oral↗
PubMed1991

Exogenous progesterone and embryo survival in Booroola-cross ewes.

To investigate if exogenous progesterone improves embryo survival, 209 multiparous Booroola Merino x South Australian Merino ewes, heterozygous for the F gene (F+) were allocated to seven treatment groups and inseminated at a synchronized oestrus. Six groups received progesterone from controlled internal drug release G dispensers on the following days after ovulation: 4-7, 4-11, 4-14, 7-11, 7-14 and 11-14. Concentration of peripheral progesterone increased (P less than 0.05) in most supplemented groups, but there were no significant differences in pregnancy rates between treatments. However, the number of fetuses per pregnancy was increased for progesterone treatments starting on Day 4 (Days 4-7, 4-11 and 4-14 combined v. control; P less than 0.05) and for all supplemented treatments compared with the control (P less than 0.05).

Animals↗
PubMed1991

Evaluation of memory dysfunction following experimental brain injury using the Morris water maze.

Memory dysfunction, a common clinical feature of traumatic brain injury (TBI), is thought to be related to secondary damage of key anatomic structures in the brain, including the hippocampus. In the present study, we have characterized and evaluated a novel experimental paradigm using the Morris water maze (MWM) technique, to measure post-TBI memory retention after lateral (parasagittal) fluid percussion (FP) brain injury in rats. Male Sprague-Dawley rats (n = 37) received a total of 20 training trials over 2 days in the MWM. Two and a half hours after the last training trial, the animals received FP brain injury of moderate severity (2.3 atmospheres, n = 12), high severity (2.6 atm, n = 13), or no injury (n = 12). Forty-two hours after FP brain injury, we observed a highly sufficient memory dysfunction in animals from both injury groups compared to the uninjured group (p less than 0.001). The degree of memory dysfunction was found to be directly related to the severity of injury, with the high severity group scoring significantly worse than the moderately injured group (p = 0.15). In addition, hippocampal cell loss was observed after brain injury, but only unilaterally. These data suggest that lateral FP brain injury causes memory dysfunction possibly related to concurrent hippocampal cell loss and that posttraumatic memory deficits may be sensitively quantitated using the memory testing paradigm described.

Animals↗
PubMed1991

Simultaneous prepubertal onset of panic disorder, night terrors, and somnambulism.

Concurrent acute onset of night terrors, somnambulism, and spontaneous daytime panic attacks meeting the criteria for panic disorder is reported in a 10-year-old boy with a family history of panic disorder. Both the parasomnias and the panic disorder were fully responsive to therapeutic doses of imipramine. A second case of night terrors and infrequent full symptom panic attacks is noted in another 10-year-old boy whose mother has panic disorder with agoraphobia. The clinical resemblance and reported differences between night terrors and panic attacks are described. The absence of previous reports of this comorbidity is notable. It is hypothesized that night terror disorder and panic disorder involve a similar constitutional vulnerability to dysregulation of brainstem altering systems.

Anxiety Disorders↗
PubMed1991

Arterial properties of early hypertension.

In addition to high blood pressure, hypertension is characterised by metabolic and cardiovascular abnormalities, including decreased arterial compliance. To evaluate arterial involvement in early hypertension, we have employed a technique that analyses the arterial pulse wave contour to separately quantify proximal compliance (aorta and large arteries) and distal compliance (small arteries and arterioles). Proximal compliance was 24% lower in patients with borderline (diastolic BP 90-99 mmHg, n = 22) and 33% lower in patients with established (n = 19) hypertension than in normals (n = 15); distal compliance was 58% and 61% lower. These differences were not age-dependent, for in 27 age-matched pairs, proximal and distal compliances were 22% (P less than 0.01) and 55% (P less than 0.01) lower in hypertensives (diastolic BP greater than or equal to 95 mmHg) than in normotensives. Moreover, independent of BP or age, both proximal (P less than 0.05) and distal (P less than 0.01) compliance values were significantly lower in subjects with a family history of hypertension than in those without. Proximal compliance correlated inversely with indices of BP variability and heart work measured by automated whole-day blood pressure monitoring. Thus, changes in the elastic properties of the distal arterial circulation, reflected by decreased compliance, occur at the initiation of hypertension and may be an early diagnostic marker. Low proximal compliance appears to be associated with established hypertension, and might be a determinant of cardiovascular prognosis.

Adult↗
PubMed1991

Observer accuracy and confirmation of the important role of abnormal ST/T time course behavior in the evaluation of stress electrocardiograms.

Routine exercise electrocardiography has been criticized for yielding too many so-called "false-positive" results. Recent studies in our institution indicate that evaluation of the time course behavior of ST segment and T wave (ST/T) changes after cessation of exercise differentiates ischemic from non-ischemic ("false-positive") stress electrocardiograms (SEs). Our method of assessing time course behavior is clarified. The principal aim of this study was to determine the accuracy of experienced observers in making this differentiation. Records of consecutive patients undergoing coronary arteriography over a 2 year period were reviewed and 30 with SEs judged positive for ischemia by the widely accepted ST/T configurational criteria alone were selected at random for the investigation. Sixteen subjects had normal coronary angiograms and had therefore previously been regarded as having false-positive SEs. Fourteen patients had at least one significantly (> 70%) stenosed coronary artery which was our yardstick for ruling that true myocardial ischemia, due to epicardial coronary artery disease (CAD), was present. Five observers, familiar with post-exercise ST/T time course patterns, independently and "blindly" analyzed all 30 configurationally abnormal SEs. Observers were informed only of the patient's age and sex; they were thus unaware of symptoms, exercise variables, coronary anatomy and the number of patients in the 2 groups. The observer consensus for ischemia of SEs using time course analysis was: total test accuracy 87%, sensitivity 79%, specificity 94%, positive predictive value 92% and negative predictive value 83%. Because all 30 patients had ST/T abnormalities, results of the sample for ischemia based on configurational criteria alone were sensitivity 100%, specificity 0% and positive predictive value 47%. We concluded that time course analysis plays a crucial role in evaluating SEs and that exercise electrocardiography remains a safe, cost-effective and reliable method of screening many asymptomatic, as well as symptomatic, subjects for CAD.

Coronary Angiography↗
PubMed1991

Applications of ambulatory blood pressure monitoring in clinical practice.

Traditionally, blood pressure has been measured by the sphygmomanometer in the medical office. There is growing evidence, however, that office blood pressures may not be typical of values throughout the day. Between 20% and 30% of patients diagnosed with hypertension in the office actually are normotensive at other times. Ambulatory blood pressure monitoring with small, portable devices that automatically measure blood pressure every few minutes throughout the day appears to be an appropriate tool when "white-coat" hypertension is suspected--i.e., for individuals whose hypertension in the physician's office is not associated with other physical or historical evidence for cardiovascular disease or with other risk factors. Used prudently, ambulatory monitoring is a cost-effective technique that potentially can prevent unnecessary treatment of patients. Moreover, whole-day measurements may correlate more closely than office measurements may correlate more closely than office measurements do with findings of cardiovascular disease. This new approach also has highlighted the circadian pattern of blood pressure, especially the sharp early to mid-morning increase that coincides with an increased tendency to major cardiovascular events. This has focused attention on directing antihypertensive therapy towards the morning hours. Ambulatory monitoring is now used routinely in studies of antihypertensive drugs. This technique has no placebo effect and takes fewer patients to assess drug efficacy than do conventional methods.

Antihypertensive Agents↗
PubMed1990

Bezafibrate and simvastatin (MK-733) in the treatment of primary hypercholesterolaemia.

Simvastatin, a new 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor, was compared to bezafibrate, a fibric acid derivative, in an open cross-over placebo-controlled study. Bezafibrate was administered as a 200 mg dose 3 times daily, while simvastatin dosage ranged from 10 mg to 40 mg once daily at night. Bezafibrate produced a non-significant 13.1% (P = 0.113) decrease in total cholesterol (TC), a 20.7% (P less than 0.05) decrease in low-density lipoprotein cholesterol (LDL-C), an increase of 26.5% (P less than 0.01) in high-density lipoprotein cholesterol (HDL-C) and an improvement in the HDL:LDL ratio of 77.3% (P less than 0.01). Simvastatin 10 mg and 20 mg daily reduced TC by 18.6% and 22.6%, respectively, and LDL-C by 23.9% and 28.6% respectively (P less than 0.01), while no significant increase was noted in HDL-C. Simvastatin 40 mg daily reduced TC and LDL-C by 27.1% and 37.6%, respectively (P less than 0.01), increased HDL-C by 32.0% (P less than 0.05) and improved on the HDL:LDL ratio by 130.8% (P less than 0.01). This showed improvements over bezafibrate of 13.5% for TC, 18.9% for LDL-C, 6.0% for HDL-C and 55.8% for HDL:LDL ratio. It was concluded that simvastatin was well tolerated and had significant hypocholesterolaemic effects when taken once daily.

Adult↗
PubMed1990

Effects of therapy with diet and simvastatin on atherosclerosis in hypercholesterolemic patients.

We evaluated the effect of cholesterol reduction on atherosclerotic coronary artery lesions using diet and simvastatin, a potent HMG CoA reductase inhibitor. Fifteen subjects aged 28-69 years (mean 44), each of whom demonstrated significant (greater than 50%) narrowing of a coronary artery and a baseline cholesterol level greater than 278 mg/dl, were studied. Coronary arteriography was performed prior to and after 20 +/- 2.5 months of therapy. A 42% reduction in total serum cholesterol, a 52% reduction in LDL cholesterol, and an 87% increase in the HDL/LDL cholesterol ratio (p less than 0.01) were achieved. Pretreatment and posttreatment angiograms were reviewed by three experienced angiographers with temporal order masked. Improvement in the overall status of coronary atherosclerotic lesions was demonstrated in two patients (13%), while deterioration occurred in one patient (7%). No overall change was found in the remaining 12 patients (80%). We conclude that a cholesterol-lowering regimen using a nonatherogenic diet and simvastatin therapy may at least stabilize coronary atherosclerosis.

Adult↗
PubMed1990

Real-time ultrasound imaging for predicting ovine fetal age.

Fetal head width and thoracic depth were observed via real-time ultrasound imaging in 12 single-, 12 twin- and 4 triplet-bearing BooroolaxSouth Australian Merino ewes at weekly intervals during mid pregnancy. Fetal age varied by a maximum of 24 h. Relationships between fetal age and the linear measures (head width, thoracic depth) were determined within litter size categories, using both linear and quadratic terms. All relationships tested for linearity were statistically significant (P<0.05). A curvilinear relationship (P<0.05) was observed for fetal age and thoracic depth of twin fetuses. Significant (P<0.05) curvilinear relationships were also observed for fetal age and head width, and fetal age and thoracic depth when litter size data were pooled. We conclude that head width and thoracic depth are acceptable linear measurements for estimating fetal age in the ovine species. Implications of these results for research and for the commercial field are discussed.

Journal Article↗
PubMed1990

Factors influencing lamb survival in a high fecundity Booroola Merino x South Australian Merino flock.

The effects of year of lambing, age of ewe and litter size on lamb survival and birthweight, and the effects of ewe mating weight and pregnancy wastage (ovulation rate minus litter size) on birthweight were examined in Booroola Merino x South Australian Merino ewes. Year of lambing, litter size and their interaction were significant (P<0.001) sources of variation for lamb survival. When birthweight was included as a linear and quadratic covariate for lamb survival, year of lambing and litter size and their interaction remained as statistically significant sources of variation. Year of lambing, litter size and pregnancy wastage contributed significantly (P<0.05) to variation in birthweight. Ewe liveweight at mating was not an important source of variation (P>0.05). Birthweight was significantly (P<0.05) reduced with an increase in pregnancy wastage. Improvement of birthweight of multiple birth lambs has some potential for increasing lamb survival. Other factors influencing lamb survival (year of lambing, litter size, pregnancy wastage) require further study so that strategies for reducing lamb loss in high fecundity Merino flocks can be developed.

Journal Article↗
PubMed1990

Fertilization and embryo loss in Booroola Merino x South Australian Merino ewes: Effect of the F gene.

The effects of Booroola genotype (F+, ++); the number of ovulations per ewe (one, two or three); and the age of a ewe (2.5 yr vs 3.5 to 6.5 yr) on the percentage of ova fertilized, embryo loss and fetal loss were examined in Booroola x South Australian Merino ewes slaughtered on Days 4, 21 and 90 after insemination. Ewes slaughtered on Day 90 were examined by real-time ultrasound imaging (RUI) on Day 45. Fertilization failure was independent of ewe genotype, ovulation rate and age of ewe, and it was not an important source of wastage (F+, 9.4%; ++, 6.7%). Most embryo loss occurred during the first 21 d (F+, 54.7%; ++, 40.3%). Interpretation of the effects of genotype and ovulation rate on embryo wastage measured on Days 21, 45 and 90 was obscured by significant (P < 0.05) genotype and ovulation rate interactions with the day of slaughter/RUI. The effect of age on embryo loss was not significant (P > 0.05). Reasons for the high rate of wastage observed in this experiment require further study.

Journal Article↗
PubMed1990

Panic disorder on a child psychiatric consultation service.

In a review of all cases seen from 1984 to 1988 by the psychiatric consultation-liaison service of a tertiary referral pediatric hospital, four cases of definite panic disorder meeting DSM-III-R criteria were identified. Three of these children were referred to the consultation service after intensive investigation of physical complaints had failed to yield a diagnosis. These cases of panic disorder differed from those previously reported in child psychiatric populations by their relative absence of psychiatric comorbidity. This suggests that uncomplicated panic disorder may present with primarily somatic symptoms in pediatric subspecialty clinics, while panic disorder, complicated by behavioral or emotional disturbance, is more likely to present directly to child psychiatric services. Children presenting with somatic symptoms are at risk for receiving nonproductive investigations while having delayed diagnosis and treatment of the panic disorder.

Adolescent↗
PubMed1990

Use of hematopoietic growth factors for treatment of aplastic anemia.

The recent discovery and manufacture of recombinant human hematopoietic growth factors offers a novel approach to treating patients with aplastic anemia. There are ongoing preclinical trials of a number of recombinant proteins that demonstrate remarkable hematopoietic activity in a variety of bone marrow failure states. Moreover, there are preliminary results of phase I/II trials of the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with aplastic anemia. It appears that this factor, the first to reach the stage of actual clinical trials, effectively increases proliferation of myeloid cellular elements of the peripheral blood and bone marrow, particularly in patients with milder forms of aplastic anemia. The side effects of GM-CSF at low to moderate doses of the growth factor (less than 16 micrograms/kg/day) appear tolerable. These results suggest that GM-CSF holds promise as a therapeutic option for patients with aplastic anemia. Long-term clinical trials will be needed to assess accurately the role that GM-CSF and other promising hematopoietic growth factors can play in the treatment of this disease, relative to other therapies such as antithymocyte globulin and bone marrow transplantation.

Anemia, Aplastic↗