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D H Smith

Publications and source records attributed to D H Smith.

At least 145 records · Page 8Linked to original sources
PubMed1994

Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs.

We describe a strategy for producing human monoclonal antibodies in mice by introducing large segments of the human heavy and kappa light chain loci contained on yeast artificial chromosomes into the mouse germline. Such mice produce a diverse repertoire of human heavy and light chains, and upon immunization with tetanus toxin have been used to derive antigen-specific, fully human monoclonal antibodies. Breeding such animals with mice engineered by gene targeting to be deficient in mouse immunoglobulin (Ig) production has led to a mouse strain in which high levels of antibodies are produced, mostly comprised of both human heavy and light chains. These strains should provide insight into the adoptive human antibody response and permit the development of fully human monoclonal antibodies with therapeutic potential.

Adult↗
PubMed1994

(S)-emopamil attenuates acute reduction in regional cerebral blood flow following experimental brain injury.

We examined the effects of (S)-emopamil, a phenylalkylamine calcium channel blocker with serotonin receptor antagonist properties, on regional cerebral blood flow (rCBF) following experimental brain injury in the rat. Animals were subjected to fluid percussion brain injury of moderate severity (2.1 atm), and received (S)-emopamil (20 mg/kg, i.p., n = 10) or saline (n = 10) at 20 minutes postinjury and 2.5 hours after the first injection of the drug. Consecutive rCBF measurements were performed: (1) prior to injury, (2) 15 minutes, (3) 90 minutes, and (4) 4 hours postinjury, using the radiolabeled microsphere technique. Brain injury produced an acute and significant reduction of rCBF at 15 minutes postinjury in all the regions examined (p < 0.05). At 90 minutes postinjury, rCBF remained significantly depressed in the forebrain regions. All brain regions showed a recovery of rCBF to normal by 4 hours following injury in saline-treated animals, with the exception of injured left parietal cortex and bilateral hippocampi, where rCBF remained significantly depressed. A significant attenuation of the trauma-induced reduction in rCBF was observed at 70 minutes after the first administration of (S)-emopamil in the forebrain regions and cerebellum (p < 0.05). Following the second (S)-emopamil injection, the significant improvement in rCBF observed in left injured cortex was maintained. These results suggest that (S)-emopamil may be efficacious in reversing post-traumatic alterations in rCBF, which may contribute to the post-traumatic pathophysiologic sequelae.

Animals↗
PubMed1994

A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension.

The primary objective of this study was to compare the antihypertensive efficacy and safety of intravenously administered nicardipine with that of intravenous nitroprusside (SNP) in patients with severe hypertension. The study was conducted in 121 patients with severe hypertension (diastolic blood pressure [BP] > 120 mm Hg, or systolic BP > 200 mm Hg). Patients were randomized to receive intravenous nicardipine or SNP. Drugs were administered according to a predetermined dosing schedule for a 10 to 12 h period. Sixty-one patients were randomized to intravenous nicardipine and 60 to SNP. Pretreatment BP values for the nicardipine and SNP groups were 217/128 mm Hg and 219/128 mm Hg, respectively. Therapeutic response (diastolic BP < 100 mm Hg, or a decrease of > 15 mm Hg; systolic BP < 180 mm Hg, or a decrease of > 20 mm Hg) was achieved in 98% (60/61) of patients treated with nicardipine and 93% (56/60) of patients treated with SNP. The mean decreases in systolic and diastolic BP were 61 mm Hg and 40 mm Hg after 4 h of nicardipine, and 59 mm Hg and 38 mm Hg after 4 h of SNP. The mean increases in heart rate also were similar in both groups (nicardipine, 12 beats/min; SNP 10 beats/min). The mean numbers of dose adjustments per hour required to maintain the BP reductions were lower (P < .01) in the nicardipine-treated patients (0.5 +/- 0.1 times per hour) than in the SNP-treated patients (1.5 +/- 0.2 times per hour).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Safety and immunogenicity of a subunit respiratory syncytial virus vaccine in children 24 to 48 months old.

A subunit vaccine for respiratory syncytial virus (RSV) consisting of purified fusion glycoprotein (designated PFP-1) was tested in children 24 to 48 months old. Two doses of 20 micrograms (n = 13) and 50 micrograms (n = 10) were compared with a saline (n = 24) placebo control group. Local and systemic reactions, reported within 96 hours postvaccination, were mild, transient, and did not differ significantly from the control cohort. Long term follow-up through at least one, and in some cases two, RSV seasons showed no serious RSV illness in vaccinees at any time. There was, therefore, no evidence of disease enhancement postvaccination. In the 20-micrograms cohort, 92% responded to vaccination by a 4-fold increase in enzyme-linked immunosorbent titer to the F glycoprotein and 42% had a 4-fold or greater rise in neutralizing titer to the A2 virus. In the 50-micrograms cohort 100% responded by enzyme-linked immunosorbent to the F glycoprotein and 70% responded by A2-neutralizing titers. The neutralizing titers in the vaccinated cohorts were similar to those seen previously in adults. These data show the ability of the subunit vaccine to boost existing immunity and to prime for a response to natural virus exposure in children who were seronegative at the time of vaccination.

Child, Preschool↗
PubMed1994

Diagnosis of mild hypertension by ambulatory blood pressure monitoring.

BACKGROUND: Between 20% and 30% of patients with clinically diagnosed hypertension have normal blood pressure (BP) values during automated ambulatory 24-hour BP monitoring. It has not been clear, however, whether these patients can be regarded as normotensive or whether they should be treated in the same way as confirmed hypertensive patients. METHODS AND RESULTS: Ambulatory BP monitoring was performed in 88 normal control subjects and 171 hypertensive patients (office diastolic BP > or = 90 mm Hg on three visits; never treated or off treatment for more than 6 months). Hypertensive patients were classified as nonconfirmed or white coat (n = 58) if their 24-hour diastolic averages were < 85 mm Hg and at least 15 mm Hg lower than their office values. For comparisons, white coat patients were pair-matched with normal subjects by 24-hour diastolic averages and sex, and by similar age and weight; there were 40 such pairs. White coat patients were likewise pair-matched with confirmed hypertensive patients by identical office BPs (51 pairs). Participants were studied by individualized treadmill testing, Doppler echocardiography, and assays of resting plasma catecholamines, upright plasma renin and aldosterone, and lipid, glucose, and insulin concentrations. Because of the matching, compared with normal subjects, patients with white coat hypertension and normal subjects had identical 24-hour BP averages. The white coat patients exhibited slightly greater variability among individual readings (obtained each 15 minutes) throughout the day [P < .05]), but there were no differences in hemodynamic responses to exercise. Plasma norepinephrine (P < .05), renin and aldosterone (P < .01 for each), and insulin and low-density lipoprotein cholesterol levels (P < .01 for each) were higher in the white coat group, as were left ventricular septal wall (P < .05) and muscle mass (P = .07) echocardiographic measurements. When compared with the confirmed hypertensive patients, the white coat patients had higher renin (P < .01) but were otherwise similar. Within the white coat group, plasma norepinephrine correlated with total cholesterol and triglycerides (P < .05 for each), and aldosterone correlated with left ventricular mass (P < .01); there were no significant correlations within the normal control subject or confirmed hypertension groups. CONCLUSIONS: Patients with white coat hypertension differ in metabolic, neuroendocrine, and cardiac findings from normal control subjects and have greater BP variability. These changes appear to be mediated by heightened activity of the sympathetic and renin-angiotensin systems. Although these characteristics could reflect an alerting reaction in the clinic due to awareness of their diagnosis, the white coat hypertensive patients also have evidence for additional, more-sustained differences from normal subjects. Thus, this condition appears to be a true variant of hypertension.

Adult↗
PubMed1994

The quantitative buffy coat for the diagnosis of trypanosomes.

The use of quantitative buffy coat (QBC) tubes developed for malaria diagnosis is described in the diagnosis of African trypanosomiasis. One hundred and thirty-four patients with Trypanosoma gambiense were examined using QBC plus either haematocrit (HCT) or mini anion exchange centrifugation (MAEC) or both. QBC was the only method that detected all 134 patients. QBC proved to be the most sensitive diagnostic test for the detection of trypanosomes in blood. It is simple to use, gives fast results and would be a useful test at the district hospital level.

Animals↗
PubMed1994

A repressive coping style protecting from emotional distress in low-renin essential hypertensives.

OBJECTIVE: To investigate the relationship between the behavioural characteristics and specified subgroups of patients with essential hypertension. DESIGN AND METHODS: Fifty-four patients were classified into groups with a high (n = 9), normal (n = 35) or low plasma renin activity (n = 10), and were compared with 20 normotensive subjects by psychological tests. Standardized tests were used to measure anger expression, defensiveness and the subjects' psychological status (e.g. anxiety, depression). RESULTS: A repressive coping style, defined by a high defensiveness and low anxiety levels, was found significantly more often in patients with low than in patients with high plasma renin activity and normotensive subjects. The patients with high plasma renin activity scored significantly higher on suppressed anger, anxiety and interpersonal sensitivity than did those with low plasma renin activity. The scores of the normal plasma renin activity group were similar to those of the normotensive group. CONCLUSIONS: The results underline that there is not one hypertensive 'personality'. Whereas the patients with a high plasma renin activity appear to be more susceptible to emotional conflicts, the patients with low plasma renin activity report low emotional distress and maintain an apparently well-adjusted facade.

Adaptation, Psychological↗
PubMed1993

The nootropic compound BMY-21502 improves spatial learning ability in brain injured rats.

Although long-lasting cognitive dysfunction often follows clinical traumatic brain injury (TBI), few pharmacologic regimens have been developed to treat post-traumatic cognitive deficits. We have previously shown that, in the rat, experimental lateral fluid-percussion (FP) brain injury induces a profound impairment in retrograde memory. In the present study, we characterized alterations in the ability of rats to learn a novel task following lateral FP brain injury and examined the potential modulatory effects of the nootropic cognitive enhancer BMY-21502 on post-injury learning. Male Sprague-Dawley rats were subjected to lateral (parasagittal) FP brain injury of moderate severity (2.4 atm) or sham surgery (no injury). On days 7 and 8 post-injury, animals were tested in a Morris water maze for their ability to learn to navigate to a submerged, invisible platform using external visual cues. BMY-21502 (10 mg/kg) or vehicle was administered 30 min prior to the first trial on both days. A highly significant (P < 0.001) impairment in post-injury learning was observed in vehicle-treated brain-injured animals compared with vehicle-treated sham animals. Injured animals treated with BMY-21502 at one week post-injury showed significantly (P < 0.05) improvement in post-injury learning ability compared to injured animals treated with vehicle. Paradoxically, in uninjured control animals BMY-21502 treatment appeared to worsen learning scores. The results of this study indicate that BMY-21502 may be useful for attenuating the dysfunction in learning ability that occurs following TBI.

Animals↗
PubMed1993

Magnesium and ketamine attenuate cognitive dysfunction following experimental brain injury.

We evaluated the therapeutic effects of two noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, MgCl2 and ketamine, both individually and together, on cognitive dysfunction observed following parasagittal fluid-percussion (FP) brain injury in the rat. Using a modified Morris water maze technique, we found significant attenuation of post-traumatic memory dysfunction in animals treated with either MgCl2 (125 mumol) or ketamine (4 mg/kg) (P < 0.005). Combined MgCl2 and ketamine treatment also preserved memory function (P < 0.005), with no apparent additive effect.

Amnesia, Retrograde↗
PubMed1993

Comparison of bisoprolol with atenolol for systemic hypertension in four population groups (young, old, black and nonblack) using ambulatory blood pressure monitoring. Bisoprolol Investigators Group.

The antihypertensive effects of drugs are partly determined by characteristics of the patients treated. A randomized, double-blind study used 24-hour ambulatory blood pressure (BP) monitoring to compare the effects of 2 beta blockers, bisoprolol (10 to 20 mg; n = 107) and atenolol (50 to 100 mg; n = 96), administered once daily in 4 population groups. After a 4-week placebo period, patients with an office diastolic BP between 95 and 114 mm Hg were stratified according to race and age, and were randomly assigned to treatment with bisoprolol or atenolol for 8 weeks. BP averages measured by automated monitoring for the 24-hour periods were compared between groups. In elderly patients, the reductions in both average 24-hour systolic and diastolic BP were greater with bisoprolol than with atenolol (13 +/- 3/13 +/- 1 mm Hg [n = 23] vs 4 +/- 2/6 +/- 1 mm Hg [n = 30]; p < 0.01). Similarly, bisoprolol produced greater reductions in average 24-hour diastolic BP than did atenolol in nonblack patients (16 +/- 2/12 +/- 1 mm Hg [n = 85] vs 12 +/- 2/9 +/- 1 mm Hg [n = 83]; p = 0.02). Bisoprolol and atenolol were similar in the black (10 +/- 5/9 +/- 3 mm Hg [n = 22] and 10 +/- 6/6 +/- 3 mm Hg [n = 13], respectively) and young (15 +/- 1/11 +/- 1 mm Hg [n = 84] and 16 +/- 2/10 +/- 1 mm Hg [n = 66], respectively) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Use of immunoplot analysis for the identification of immunodominant non-variant antigens of Trypanosoma brucei rhodesiense.

The application of the 'immunoplot' technique to the analysis of a complex series of immunoblots is described. A number of isolates of Trypanosoma brucei rhodesiense blood forms from Uganda, Kenya and Zambia were separated by SDS-PAGE under reducing and non-reducing conditions and transferred by immunoblotting onto nitrocellulose paper. The separated antigens from each isolate were then probed with sera from European and endemic controls, and a large panel of sera from confirmed trypanosomiasis patients. The resulting series of immunoblots was examined by the 'immunoplot' technique, which involves comparing frequencies of recognition of each band by the sera of controls and patients. A number of antigens of possible diagnostic interest were identified; a bad of 37/38 kDa was found to be recognised with high frequency (> 55%) by the sera of patients and virtually not at all by control sera under both reducing and non-reducing conditions. When this band was combined with one of the other frequently recognised bands, recognition by patient sera was raised to 92% (reduced) and 76% (non-reduced). This did not appear to be isolate-specific. The 'immunoplot' technique has potential for further development and wider use in immunoepidemiology and immunodiagnostic research.

Animals↗
PubMed1993

Metabolic characteristics of hypertension: importance of positive family history.

This study was performed to compare metabolic and endocrine characteristics of untreated hypertensive patients and normal controls. Measurements were made in age-matched, body mass index (BMI) matched, normotensive patients with (n = 40; age = 53; BMI = 28) and without (n = 39; age = 54; BMI = 27) a family history of hypertension and hypertensive patients with (n = 38; age = 53; BMI = 28) and without (n = 25; age = 54; BMI = 29) a family history of hypertension. Norepinephrine, renin activity, and total cholesterol blood concentrations were similar in normotensive patients with a positive family history of hypertension and in hypertensive patients with or without a family history. Similarly, there were no differences in plasma insulin concentrations or insulin/glucose ratios between the normotensive patients with a family history of hypertension and hypertensive patients with or without a family history. But in all three groups the values were significantly greater (at least p < 0.05 for each) than in the normotensive patients without a family history. Increases in systolic blood pressure during treadmill testing were 51 +/- 4 mm Hg in the normotensive patients with a family history, 50 +/- 3 mm Hg in hypertensives with a family history, and 45 +/- 5 mm Hg in hypertensives without a family history; these changes were all less (p < 0.05 for each) than in normotensives without a family history (65 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Application of ambulatory blood pressure monitoring in differentiating between antihypertensive agents.

PURPOSE: This multicenter, double-blind, parallel group study assessed the usefulness of the ambulatory blood pressure monitoring (ABPM) technique in differentiating between the once-daily administration of the beta blockers bisoprolol (10 to 20 mg) and atenolol (50 to 100 mg) in terms of efficacy and duration of action. PATIENTS AND METHODS: The study population consisted of 659 patients with essential hypertension and an average office diastolic blood pressure (BP) between 95 and 115 mm Hg after 4 weeks of placebo treatment. Office BPs were recorded at the end of the 24-hour dosing interval (trough). ABPM was performed in 11 of the 28 institutions participating in this study in a total of 203 patients. These procedures were performed at the end of the placebo phase and again after 8 weeks of active treatment. RESULTS: With the use of conventionally measured office BPs, the two drugs significantly (p < 0.001) decreased trough systolic and diastolic BPs to a similar extent. By 24-hour monitoring, bisoprolol demonstrated a 33% greater reduction in whole-day average diastolic BP than did atenolol (11.6 +/- 0.7 mm Hg versus 8.7 +/- 0.8 mm Hg, p < 0.01). Significant treatment differences in systolic (p < 0.05) and diastolic (p < 0.01) BPs were also noted for bisoprolol compared with atenolol during the final 4 hours of the dosing interval (-13.2 +/- 1.5/-10.9 +/- 1.0 mm Hg versus -8.9 +/- 1.6/-7.3 +/- 1.1 mm Hg, respectively), and over the time period 6:00 AM to noon (-14.2 +/- 1.3/-11.5 +/- 0.9 mm Hg versus -9.9 +/- 1.4/-7.7 +/- 0.9 mm Hg). CONCLUSIONS: Whereas conventional BP measurements did not detect differences in the antihypertensive effects of the beta blockers bisoprolol and atenolol, ABPM revealed significant treatment differences in both the efficacy and duration of action of these two agents. These findings indicate the power of this technique to discriminate potentially important differences between apparently similar antihypertensive drugs.

Adult↗
PubMed1993

The relationship of arterial compliance with endothelial-derived proteins of the hemostatic system.

Cardiovascular risk factors associated with hypertension include alterations in arterial compliance and an increased tendency to thrombosis. In this study we examined the relationship between arterial compliance and endothelial derived components of the hemostatic system: von Willebrand factor (vWF) and tissue plasminogen activator (t-PA). Ten males (4 normal and 6 untreated hypertensives, 41 +/- 12 years) were studied. Compliance of proximal (large vessel) and distal (small vessel) arteries was measured by intraarterial pulse wave analysis; left ventricular wall thickness by echocardiography; and vWF and t-PA by immunoassay of plasma obtained before and immediately after maximum treadmill exercise. Baseline t-PA and vWF correlated inversely with distal compliance (r = -0.74, p = 0.01; r = -0.56, p = 0.09). Exercise strengthened the relationship between vWF and both distal compliance (r = -0.56 to r = -0.86) and proximal compliance (r = -0.44 to r = -0.70). Moreover, post-exercise levels of vWF and t-PA were each significantly related to left ventricular posterior wall and septal thickness. Of note, these protein concentrations correlated more strongly with arterial compliance and left ventricular wall thickness than with blood pressure. Thus, arterial compliance and left ventricular wall thickness appear to be more powerful than blood pressure as predictors of the endothelial release of vWF and t-PA in response to exercise. These findings indicate that some of the key cardiac and arterial characteristics of hypertension might be linked to increased endothelial reactivity to hemodynamic stress.

Adult↗
PubMed1993

Effect of nutrition during pregnancy on fetal growth and survival in Fec(B) Booroola x South Australian Merino ewes.

The effect of nutritional manipulation during mid and late pregnancy on fetal growth and survival in high fecundity (Fec(B) Fec(+)) Merino ewes was examined. A total of 4 treatment groups was utilized in each of 3 years (1987, 1988 and 1989); and 2 groups were given low nutrition during mid pregnancy while 2 groups received high nutrition during this period. One group from each of these treatments subsequently received a high protein diet 1 to 2 weeks prior to term. Differential feeding during mid pregnancy resulted in the high and low treatment groups varying by 7.5 and 5.0 kg liveweight at Days 100 and 135 of pregnancy, respectively. Fetal survival was not improved by variation in nutritional intake during mid pregnancy (P>0.05) and neither were placental and fetal growth (P>0.05), as indicated by observations on cotyledon diameter and fetal head width, respectively. However, fetal survival during late pregnancy was reduced by a high level of nutrition during both mid and late pregnancy (P<0.05).

Journal Article↗
PubMed1993

Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus.

Memory dysfunction following mild human traumatic brain injury (TBI) is a common clinical observation, but the pathologic substrate underlying this loss of function has not been well-characterized. In the present study, we examined the effects of a mild lateral fluid percussion (FP) brain injury on memory dysfunction, neuronal cell loss in specific regions of the hippocampus, and breakdown of the blood-brain barrier (BBB). A Morris Water Maze (MWM) memory paradigm was used to assess memory retention in rats 42 h after lateral FP brain injury (n = 11) or sham injury (n = 10). At the completion of cognitive testing, animals were sacrificed and neuronal cell loss in the hippocampi was examined with Nissl staining. Immunoreactivity to anti-rat IgG was used to evaluate the extent of BBB disruption. A significant correlation was observed between posttraumatic memory scores and neuronal loss in the hilus of the dentate gyrus (p < 0.005). To our knowledge, these observations are the first to suggest an association between cognitive deficits following a mild experimental brain injury and neuropathological changes in the hippocampus.

Animals↗