Development of ocular hypertension in congenitally buphthalmic rabbits.
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Animals↗
Biomedical subjects
T D Smith
Publications and source records attributed to T D Smith.
%VO2max versus %HRmax regressions for six modes of exercise.
The purpose of the study was to compare the %VO2max versus %HRmax regression equations developed from data collected during incremental work on six exercise modes: treadmill (T), cycle (C), skier (S), shuffle skier (SS), stepper (ST), and rower (R). Ten active males were habituated to all modes and then performed an incremental test to maximum on each mode. Mode order was assigned by Latin square sequences and the tests were separated by at least 72 h. VO2 and HR were recorded at each increment. Regression analyses were performed using SAS-GLM. Regressions for T, S, SS, and ST were not significantly different. C had a lower intercept and higher slope, while R had a higher intercept and lower slope than the other exercise modes. These results suggest that weight bearing exercise modes have similar %VO2max-%HRmax regressions. However, weight supported and arm exercise modes appear to have different regressions.
Adult↗
Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells.
Bone marrow failure is a consistent feature of Fanconi anemia (FA) but it is not known whether the bone marrow failure is a direct and specific result of the inherited mutation or a consequence of accumulated stem cell losses resulting from nonspecific DNA damage. We tested the hypothesis that the protein encoded by the FA group C complementing gene (FACC) plays a regulatory role in hematopoiesis. We exposed normal human lymphocytes, bone marrow cells, endothelial cells, and fibroblasts to an antisense oligodeoxynucleotide (ODN) complementary to bases -4 to +14 of FACC mRNA. The mitomycin C assay demonstrated that the antisense ODN, but not missense or sense ODNs, repressed FACC gene expression in lymphocytes. Treatment with the antisense ODN substantially reduced, in a sequence-specific fashion, cytoplasmic levels of FACC mRNA in bone marrow cells and lymphocytes. Escalating doses of antisense ODN increasingly inhibited clonal growth of erythroid and granulocyte-macrophage progenitor cells but did not inhibit growth of fibroblasts or endothelial cells. The antisense ODN did not inhibit growth factor gene expression by low density bone marrow cells or marrow-derived fibroblasts. We conclude that, while the FACC gene product plays a role in defining cellular tolerance to cross-linking agents, it also functions to regulate growth, differentiation, and/or survival of normal hematopoietic progenitor cells.
Base Sequence↗
Anterior paraseptal cartilage development in normal and cleft lip and palate human fetal specimens.
As part of an ongoing study of age-related variation in fetal cleft lip and palate nasal capsule morphology, anterior paraseptal cartilage development was examined histologically in a sample of nine complete cleft lip and palate human fetuses, and 20 without clefts ranging in age from 8 to 21 weeks. A computer reconstruction technique was used to quantify lengths, volumes, and generate growth curves from various regression equations. Anterior paraseptal cartilage length was seen to change in a sigmoidal fashion while volume changes were best described by a logarithmic curve for both groups, with the steepest increases from 15 to 21 weeks. Cleft specimens exhibited significantly different growth rates (line slopes) for both length and volume dimensions compared with the normal specimens. The larger, for age, cartilages were associated with an enlarged, inferior border of the nasal septal cartilage and vomer in the cleft sample. These results are consonant with previous findings in this cleft fetal sample of other enlarged midline structures (i.e., nasal septal cartilage and vomer). Results suggest that growth abnormalities in one or all of these structures may be yet another mechanism for early nasal airway impingement and reduction in cleft lip and palate neonates.
Case-Control Studies↗
Development of a strain of rabbits with congenital simple nonsyndromic coronal suture synostosis. Part I: Breeding demographics, inheritance pattern, and craniofacial anomalies.
The lack of an animal model of congenital coronal suture (CS) synostosis has prompted the widespread use of an experimental rabbit model using adhesive immobilization of the CS. Such postnatal models have helped make significant scientific contributions but may still not fully represent all aspects of the human congenital condition. In the March 1993 issue of The Cleft Palate-Craniofacial Journal we reported a female rabbit born in our laboratory with complete bilateral CS synostosis. This follow-up study presents our attempts to breed this animal and establish a strain of craniosynostotic rabbits. To date, we have accomplished 10 back- and intercrosses with these animals and have produced a total of 71 live offspring; 10 animals exhibited complete nonsyndromic unilateral (plagiocephalic) or bilateral (brachycephalic) CS synostotic deformities at birth, and 19 animals exhibited partial CS synostosis that showed more than 75% growth retardation across the CS (well below the 95% confidence interval for normals). Results revealed that gestational time and litter size averages were consistent with those reported for the strain, although the average litter size decreased with increased inbreeding. By 1.5 weeks of age the completely synostosed animals already exhibited brachycephalic cranial vaults and midfacial hypoplasia compared to unaffected siblings. Initial pedigree analysis suggested an autosomal dominant inheritance pattern with incomplete penetrance and variable expressivity. The development of such a congenital rabbit model may prove useful in helping to understand the etiopathogenesis of this condition in human populations.
Animals↗
Development of a strain of rabbits with congenital simple nonsyndromic coronal suture synostosis. Part II: Somatic and craniofacial growth patterns.
In the March 1993 issue of The Cleft Palate-Craniofacial Journal we reported a female rabbit born in our laboratory with complete bilateral coronal suture (CS) synostosis. This follow-up study presents our attempts to breed the animal and establish a strain of craniosynostotic rabbits. The second part of this study presents longitudinal somatic and craniofacial growth data in offspring with coronal suture synostosis. Serial growth data from 72 animals were collected for the present study. The sample consisted of 11 animals (10 offspring and the original female) with complete nonsyndromic unilateral (plagiocephalic) or bilateral (brachycephalic) CS synostosis, 19 animals with partial CS synostosis, and 42 unaffected control litter mates. At 10 days of age, all animals had radiopaque amalgam markers placed on either side of the frontonasal, coronal, anterior lambdoidal, and sagittal sutures. Body weights and serial lateral and dorsoventral head radiographs were taken at 1.5 (10 days), 6, 12, and 18 weeks of age. All animals showed similar body weights at 1.5 weeks of age, while completely synostosed animals exhibited a slight (about 12%), but significantly (p < .001) lowered body weight by 18 weeks of age. Results revealed that by 1.5 weeks of age the completely synostosed animals already exhibited brachycephalic cranial vaults, midfacial hypoplasia, and increased flattening of the cranial base compared to unaffected siblings. This pattern continued through 18 weeks of age, with the partially synostosed animals exhibiting intermediate morphologies.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The prevalence of diabetic retinopathy and maculopathy and their risk factors in the non-insulin-treated diabetic patients of an English town.
A total population study of the ocular status of all known non-insulin-treated diabetic patients resident in the English town of Melton Mowbray has been conducted. The population prevalence of non-insulin-treated diabetes in the town was 6.7/1000. There were 215 patients in the target population, with 65% of the resident survivors participating in the study. Further data on ocular status were gathered from hospital records, bringing the total percentage for whom some information on ocular status was available to 74%. Corrected Snellen acuity was 6/12 or better in 76% of patients and the over-all prevalence rate for any diabetic retinopathy was 52%, for proliferative retinopathy was 4%, and for maculopathy requiring treatment was 10%. In a multivariate analysis, risk factors for retinopathy and/or maculopathy included longer diabetic duration, female sex, higher blood pressure, the use of anti-hypertensive drugs and cigarette smoking.
Adult↗
Specific repression of granulocyte-macrophage and granulocyte colony-stimulating factor gene expression in interleukin-1-stimulated endothelial cells with antisense oligodeoxynucleotides.
Antisense oligodeoxynucleotides (ODNs) have been used to effect the specific inhibition of cellular gene expression. We have evaluated the application of this approach to the inhibition of interleukin-1 (IL-1)-induced granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) expression in cultured human umbilical vein endothelial cells. Antisense ODNs or control ODNs (sense ODNs or missense ODNs containing random base substitutions) were added to cultures of endothelial cells, the cells were induced with IL-1 alpha, and the conditioned media were assayed for GM-CSF and G-CSF by quantitative bioassays and for immunoreactive GM-CSF by enzyme immunoassay. Antisense ODNs complementary to the first 15 or 18 bases of the translation start sites of GM-CSF or G-CSF mRNAs inhibited, in a concentration-dependent fashion, the IL-1-stimulated expression of the corresponding factor, but did not affect expression of the other factor. Control ODNs did not affect GM-CSF or G-CSF expression. Exposure to a GM-CSF antisense ODN, but not a control ODN, substantially reduced cytoplasmic GM-CSF mRNA levels in IL-1-stimulated endothelial cells. Neither ODN affected levels of endothelial leukocyte adhesion molecule (ELAM)1 or glyceraldehyde-3-phosphate dehydrogenase mRNAs. We conclude that antisense ODNs complementary to the translation start sites of GM-CSF or G-CSF mRNAs inhibit expression of the corresponding factor in a sequence-specific fashion and this effect is mediated, at least in part, by reduction in the cytoplasmic level of the targeted mRNA. Moreover, IL-1-induced GM-CSF or G-CSF expression does not depend on expression of the other factor.
Animals↗
Further pharmacological characterization of [3H]idazoxan binding sites in rat brain: evidence for predominant labeling of alpha 2-adrenergic receptors.
In addition to binding to alpha 2-adrenergic receptors, the antagonist [3H]idazoxan has been reported to bind to non-adrenergic sites in a number of tissues and species. In the present study, the pharmacological nature of [3H]idazoxan binding sites in rat brain slices has been examined using radioligand binding and autoradiographic techniques. In Na2KHPO4 buffer, four drugs with high affinity for alpha 2-adrenergic binding sites were potent inhibitors of [3H]idazoxan binding, with the rank order of potency being RX821002 greater than phentolamine greater than yohimbine greater than (-)epinephrine. Non-linear regression analysis resolved all competition curves into two components, with the high affinity site representing the majority of total [3H]idazoxan binding. In autoradiographic studies performed in Na2KHPO4 buffer, all alpha 2-selective ligands displaced greater than or equal to 75% of total [3H]idazoxan binding to most brain regions. These findings indicate that the major component of [3H]idazoxan binding was to sites that are alpha 2-adrenergic in nature. [3H]Idazoxan binding was also examined in glycylglycine buffer. In contrast to binding in Na2KHPO4 buffer, the proportion of low affinity sites was significantly increased in glycylglycine buffer. Autoradiographic studies confirmed these findings. These pharmacological data are consistent with our previously reported conclusions that, under appropriate assay conditions, [3H]idazoxan predominantly labels alpha 2-adrenergic binding sites in rat brain. These sites are widely distributed and have pharmacological characteristics consistent with those previously reported for alpha 2A-adrenergic receptors.
Adrenergic alpha-Antagonists↗
Efficacy of myocardial protection with hypothermic blood cardioplegia depends on oxygen.
The role of oxygen (O2) in blood cardioplegia (BCP) remains controversial. On the one hand, O2 reduces ischemic injury between BCP infusions by maintaining energy production through oxidative pathways. On the other hand, O2 carried by blood may not be released to the tissue at 4 degrees C or potentially provides substrate for deleterious O2 radical species. This study tests the hypothesis that O2 is a critical component in myocardial protection afforded by BCP. In 17 anesthetized dogs, left ventricular performance was measured by left ventricular end-systolic pressure-volume relations using the position of the end-systolic pressure-volume relation quantitated by the left ventricular midrange volume intercept at 100 mm Hg (V100) to describe performance. After 30 minutes of global normothermic ischemia, hearts were protected with multidose 4 degrees C BCP for 1 hour of arrest. Oxygen content in BCP was adjusted to 1.1 +/- 0.2 vol% (n = 7; desaturated BCP group), 4.3 +/- 0.5 vol% (n = 5; intermediate oxygenated BCP group), or 10.2 +/- 0.6 vol% (n = 5; saturated BCP group) using a membrane oxygenator interposed in the BCP circuit and aerated with an appropriate mixture of O2, nitrogen, and carbon dioxide. After 1 hour of 37 degrees C reperfusion, 3 of the 7 dogs in the desaturated BCP group failed to generate sufficient cardiac output to discontinue bypass. In the remaining 4 dogs, severe left ventricular depression caused a rightward shift in V100 from 17 +/- 4 to 47 +/- 9 mL (p = 0.02). With intermediate BCP, all hearts were weaned from bypass with marginal left ventricular depression (V100, 20 +/- 5 versus 46 +/- 16 mL; p = 0.10). In contrast, hearts protected with saturated BCP showed no significant increase in V100 (13 +/- 4 versus 24 +/- 13 mL; p = 0.23). We conclude that O2 in BCP is critical to its myocardial protective properties.
Animals↗
N-[3H]methylscopolamine labeling of non-M1, non-M2 muscarinic receptor binding sites in rat brain.
Radioligand binding and quantitative autoradiographic techniques were used to characterize the pharmacological profile and anatomical distribution of N-[3H]methylscopolamine [( 3H] NMS)-labeled sites under assay conditions in which radioligand binding to M1 and M2 muscarinic receptors was blocked by addition of pirenzepine and AF-DX 116 (11[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b] [1,4]benzodiazepine-6-one) to the incubation buffer. Nonlinear regression analysis of saturation data demonstrated that a large proportion of atropine-displaceable [3H]NMS binding persisted in the presence of saturating concentrations of M1 and M2 blockers. The residual [3H]NMS [( 3H]NMSb) sites were widely distributed throughout rat brain and represented the predominant muscarinic receptor population. The autoradiographic distribution of [3H]NMSb sites did not correspond to that of [3H]pirenzepine or [3H]AF-DX 116, indicating that [3H]NMSb labeled non-M1, non-M2 muscarinic sites. Moreover, the pharmacological profile of [3H]NMSb differed from that of [3H]pirenzepine at M1 sites, and was inconsistent with that of M2 receptor binding sites. Although we were unable to pharmacologically distinguish subpopulations of non-M1, non-M2 binding sites, the anatomical distribution of [3H]NMSb sites corresponded to that of the combined mRNA distributions for m3 and m4.
Animals↗
Individual variation between general practitioners in labelling of hypertension.
Variation in labelling of hypertension by individual general practitioners was studied during a continuous opportunistic screening programme for hypertension in a single general practice with 12 principals. All the general practitioners agreed to label as hypertensive patients with systolic pressures of greater than or equal to 200 mm Hg or diastolic pressures of greater than or equal to 110 mm Hg on three consecutive readings. The overall number of patients labelled hypertensive at the beginning of the screening programme was 505 and this rose to 801 after five years. There was a large variation in the numbers of patients recorded as hypertensive at the start of the screening period, with numbers ranging from eight to 112 for individual practitioners. The variation persisted during the screening period, with the numbers of patients detected by individual general practitioners ranging from four to 46. The average systolic and diastolic pressures recorded among these patients also varied between doctors, and only 24 out of 187 patients had their high pressures recorded on three occasions and so fully met the criteria for diagnosing hypertension. Clearly, general practitioners are following their own individual criteria in defining hypertension and taking into account factors other than just the measured blood pressure.
Adult↗
Postischemic [Ca2+] repletion improves cardiac performance without altering oxygen demands.
The positive inotropism expected with correction of postischemic hypocalcemia might be counterbalanced by potential aggravation of reperfusion injury, in particular by calcium overload. We evaluated the effect of normalizing blood calcium concentration ([Ca2+]) on postischemic left ventricular systolic and diastolic mechanics using oxygen consumption and indices derived from pressure-diameter relations. In 10 open-chest dogs on cardiopulmonary bypass, the hearts underwent 30 minutes of normothermic global ischemia followed by one hour of multidose hypothermic (4 degrees C), hypocalcemic (0.3 mmol/L) blood cardioplegia. After reperfusion, systemic [Ca2+] had decreased to 70% of control (p = 0.017). The left ventricular inotropic state was significantly depressed from baseline (control) values, but was restored to baseline levels by resumption of normocalcemia after one hour of reperfusion. Chamber stiffness increased by 308% (p = 0.006) after hypocalcemic reperfusion but decreased significantly after [Ca2+] correction. Recovery of left ventricular performance with [Ca2+] correction did not augment myocardial oxygen consumption from the postischemic uncorrected state (5.0 +/- 0.3 mL O2/min/100 g versus 5.3 +/- 0.3 mL O2/min/100 g). We conclude that normalizing [Ca2+] after blood cardioplegia improves postischemic left ventricular performance without adversely affecting compliance or oxygen consumption.
Animals↗
Group A streptococcus-associated upper respiratory tract infections in a day-care center.
Little information is available about the epidemiology of group A streptococcal upper respiratory tract infections in child day-care centers. During an initial 3-month period, symptomatic upper respiratory tract infections associated with throat cultures or rapid antigen detection tests positive for group A streptococci developed in 55 of 214 (26%) children and adult staff in one day-care center. When the entire day-care center population (except for those receiving antibiotics at the time) was then surveyed, 52 of 146 (36%) children and two of 24 (8%) adult staff had throat cultures positive for group A streptococci. Of the 54 group A streptococcal isolates found during the survey, the three most frequently encountered serotypes were M2,T2/28 (35%), M3,T3/13 (30%), and M-NT, T25 (20%). Rapid antigen detection was performed at the same time as the throat culture in the first 98 individuals examined during the culture survey but was positive in only 11 (35%) of 31 individuals with positive throat cultures. Sensitivity of the rapid antigen test was related to degree of positivity of the throat culture but not to age. The overall group A streptococcal positivity rate was 49% for 187 children and 33% for 27 adult staff; 18 of 66 (27%) children younger than 31/2 years of age were found to have group A streptococci in their upper respiratory tracts. This is the first report of high prevalence rates of group A streptococci associated with upper respiratory tract infections in a day-care center. The group A Streptococcus may represent a significant upper respiratory tract pathogen in the day-care setting.
Adult↗
Calcium channel binding characteristics in the human heart.
The number, affinity, pharmacologic specificity and regional distribution of calcium channel binding sites in human hearts obtained at autopsy and open heart surgery were characterized using the radioligand [3H]nitrendipine. Scatchard analyses of saturation data from 6 autopsy hearts revealed a homogeneous distribution of high affinity binding sites (affinity-1 [KD] = 0.44 +/- 0.06, 0.52 +/- 0.07, 0.32 +/- 0.02, 0.30 +/- 0.03, and 0.45 +/- 0.01 nM; binding capacity [Bmax] = 30 +/- 4, 27 +/- 6, 25 +/- 7, 33 +/- 3, and 28 +/- 4 fmol/mg protein in right atrium, right ventricle, left atrium, left ventricle and ventricular septum, respectively). In ligand competition experiments, nifedipine and nitrendipine completely displaced binding with partial displacement by verapamil and 35% enhancement of binding by 10(-5) M diltiazem at 37 degrees. Analyses of right atrial appendages obtained at open heart surgery from 5 coronary artery bypass patients provided similar results (KD = 0.2 +/- 0.03 nM, Bmax = 42 +/- 2 fmol/mg protein). In addition, no significant differences in KD or Bmax were found in 3 hamster hearts assayed at the time of death or up to 18 hours postmortem at either 4 or 25 degrees. In contrast, there was a significant increase in Bmax (110 fmol/mg protein) with no change in KD (0.3 nM) in a myomectomy specimen from a patient with obstructive hypertrophic cardiomyopathy compared with either autopsy or surgical specimens. These studies illustrate the feasibility and potential advantages of studying calcium channels directly in human hearts.
Adult↗
Comparison of regional differences in cardiac myocyte dimensions in rats, hamsters, and guinea pigs.
Isolated myocytes were prepared from Sprague Dawley rats, golden Syrian hamsters, and Hartley guinea pigs to investigate regional variations in myocyte size. Cell volume (V) was measured with a Coulter Channelyzer, cell length (L) was measured directly, and cross-sectional area (CSA) was calculated from V/L. Compared to values from the left ventricle (LV), right ventricular L was shorter in the rat (P less than .01) and hamster (P less than .05) and longer in the guinea pig (P less than .01). Guinea pig atrial L was shorter (P less than .01) than L in the right ventricle (RV) but did not differ from L in the LV. No significant differences in L existed between endomyocardium, middle myocardium, and epimyocardium of the LV in all three species. In rats and hamsters, myocytes from the RV had smaller V and CSA values (P less than .01) compared to any region of the LV. A transmural gradient of cellular dimensions existed in the LV of the rat, but not in hamster, with V and CSA of endomyocardium being largest and epimyocardium smallest (P less than .01). Endomyocardial V and CSA were larger (P less than .01) than all other regions in the hamster, but the difference was not significant compared to epimyocardial V. In the guinea pig, no significant differences in V existed between RV and LV or between the three LV regions. No pattern of regional differences was seen between ventricular CSA values in the guinea pig. Guinea pig atrial V and CSA values were smaller (P less than .01) than those for ventricular myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Efficacy of beta-lactamase-resistant penicillin and influence of penicillin tolerance in eradicating streptococci from the pharynx after failure of penicillin therapy for group A streptococcal pharyngitis.
We studied the ability of dicloxacillin, a beta-lactamase-resistant penicillin, to eradicate persistent group A streptococci from the upper respiratory tract of children previously given penicillin V, and concomitantly assessed the role of antibiotic (penicillin and dicloxacillin) tolerance as a contributing factor. During a group A streptococcal pharyngitis outbreak, 66% of 324 children were found to be culture positive for group A streptococci. Ninety percent of these isolates were serotype M-1, T-agglutination pattern T-1. The treatment failure rate after initial orally administered penicillin treatment was 21% (42 of 204). These 42 children then received either a second course of penicillin V orally or a course of dicloxacillin. The resulting rates of failure to eradicate the homologous streptococcal serotype were 83% (20 of 24) and 50% (9 of 18), respectively (P less than 0.02). Of 189 streptococcal isolates tested by the gradient replicate plate method for penicillin tolerance, 18 (10%) were tolerant. In this study, penicillin-tolerant strains of group A streptococci were no more frequently isolated from children in whom initial penicillin treatment failed than from those who were successfully treated. Dicloxacillin tolerance was not a factor in failure of dicloxacillin therapy. These data, when evaluated with data from previous studies, suggest that reasons for failure to eradicate group A streptococci from the upper respiratory tract are complex, but dicloxacillin may be beneficial in some patients who fail to respond to orally administered penicillin therapy.
Child↗
Drug and chemical related deaths: incidence in the State of Maryland--1975 to 1980.
The incidence of drug and chemical related deaths was studied over a six-year period in the State of Maryland. Deaths were classified into the following categories: alcohol, carbon monoxide (CO), single drugs, multiple drugs, and narcotism. The last three categories were further subdivided as to the specific drugs or chemicals involved. Over the six-year period the number of alcohol and CO deaths remained steady, the number of barbiturate and propoxyphene deaths declined, while the number of tricyclic antidepressant drug deaths increased.
Adolescent↗