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Biomedical subjects

J S Harper

Publications and source records attributed to J S Harper.

At least 19 recordsLinked to original sources

Parathyroid hormone venous sampling prior to reoperation for primary hyperparathyroidism.

BACKGROUND: The surgical cure rate for primary hyperparathyroidismis greater than 95%. For those who have recurrent or persistent disease, preoperative localization improves reoperation success rates. Selective parathyroid venous sampling (SPVS) for intact parathyroid hormone is particularly useful when non-invasive localization techniques are negative or inconclusive. METHODS: We present all known cases (n = 13)between 1994 and 2002 who had venous sampling for localization a tour institution prior to reoperation for recurrent or persistent primary hyperparathyroidism. Comparison was made with non-invasive localization procedures. Results of invasive and non-invasive localization were correlated with surgical findings. RESULTS: Of the nine reoperated cases, eight had positive correlations between SPVS and operative findings and histopathology. SPVS did not reveal the parathyroid hormone source in one case with negative non-invasive localization procedures. Comparisons between SPVS,computerized tomography (CT), and parathyroid scintigraphy (MIBI)as expressed in terms of true positive (TP), false positive (FP)and false negative (FN) were: SPVS - TP88.8%, FP 0%, FN 11.1%; CT - TP22.2%, FP 22.2%, FN 55.5%; and MIBI - TP33.3%, FP 0%, FN 66.6%. At least seven of the nine operated cases have been cured; another remained normocalcaemic 2 weeks after subtotal parathyroidectomy. CONCLUSION: In our institution SPVS has proven to be a valuable tool in cases with recurrent or persistent primary hyperparathyroidism and negative non-invasive localization procedures.

Adult↗

Motor vehicle crash fatalities: A comparison of Hispanic and non-Hispanic motorists in Colorado.

STUDY OBJECTIVES: We compare the population-based death rates from traffic crashes in the Hispanic and non-Hispanic white populations in a single state, and compare fatally injured Hispanic and non-Hispanic drivers with respect to safety belt use, alcohol involvement, speeding, vehicle age, valid licensure, and urban-rural location. METHODS: Hispanic and non-Hispanic white motorists killed in traffic crashes in 1991-1995 were studied (n=2,272). Data from death certificates (age, sex, education, race, and ethnicity) and the Fatality Analysis Reporting System (FARS; driver, vehicle, and crash information) were merged. Average annual age-adjusted fatality rates were calculated; to compare Hispanic and non-Hispanic white motorists, rate ratios (RR) and 95% confidence intervals (CIs) were calculated. Odds ratios (ORs), adjusted for age, sex, and rural locale, were calculated to measure the association between Hispanic ethnicity and driver and crash characteristics. RESULTS: Eighty-five percent of FARS records were matched to death certificates. Compared with non-Hispanic white motorists, Hispanics had higher crash-related fatality rates overall (RR 1.75, 95% CI 1.60 to 1.92) and for drivers only (RR 1.62, 95% CI 1.41 to 1.85). After adjustment for age, sex, and rural locale, Hispanic drivers had higher rates of safety belt nonuse (OR 1.81, 95% CI 1.20 to 2.72), legal alcohol intoxication (OR 2.73, 95% CI 1.97 to 3.79), speeding (OR 1.36, 95% CI 0.99 to 1.88), and invalid licensure (OR 2.58, 95% CI 1.78 to 3.75). The average vehicle age for Hispanic drivers (10.1 years, 95% CI 9.3 to 11.0) was greater than for non-Hispanic white motorists (8.8 years, 95% CI 8.4 to 9.2). CONCLUSION: Compared with non-Hispanic whites, Hispanic drivers have higher rates of safety belt nonuse, speeding, invalid licensure and alcohol involvement, with correspondingly higher rates of death in traffic crashes. As traffic safety emerges as a public health priority in Hispanic communities, these data may help in developing appropriate and culturally sensitive interventions.

Accidents, Traffic↗

Reproducible echocardiography in juvenile sheep and its application in the evaluation of a pulmonary valve homograft implant.

Increased use of the ovine animal model in cardiovascular surgical research has created a salient need for standardized echocardiography techniques. To demonstrate a reproducible image in this species and confirm the validity of echocardiography as a diagnostic tool, we implanted 10 sheep with a pulmonary valve homograft and monitored them through weekly echocardiographic examinations until 20 weeks after implantation. We obtained good images from the left cranial and the left caudal transducer windows without needing to sedate the animals. Sedated sheep yielded adequate views from the right apical window. Echocardiographic data on the implanted homografts (including functional capacity, presence of calcification, and hemodynamic information and measurements), completely agreed with the results of the post-explantation examinations.

Animals↗

The fetal cleft palate: I. Characterization of a congenital model.

Any animal model of a human congenital anomaly established by iatrogenic methods involving intrauterine fetal manipulation has limited clinical applicability. A congenital model that more closely simulates the etiopathogenesis of a human anomaly may provide data that can more readily be extrapolated to that anomaly and, therefore, be used in diagnostic and management strategies. The present work provides a description and characterization of a congenital model of cleft palate in the goat. Palatal shelf closure normally occurs at approximately day 38 of gestation in the caprine species. Sixteen pregnant goats were gavaged twice daily during gestational days 32 through 41 [term, 145 days] with a plant slurry of Nicotiana glauca containing the piperidine alkaloid teratogen anabasine. Gross analysis and measurement of fetal clefts were performed at 60, 70, and 85 days gestation (four fetuses were studied at each time point). Seventeen clefted kids were sacrificed at specific intervals after birth (2 weeks, and 1, 3, and 6 months); after skull debridement and preparation, they were compared with 12 unclefted control kids. Complete clefting of the secondary palate occurred in 97 percent of the fetuses. In all cases, the cleft extended from the posterior aspect of the alveolar ridge to the uvula; the majority of these clefts were bilateral, with complete detachment of the vomer. Morphologically, these clefts were similar to human clefts. Eighteen percent of clefted newborn kids demonstrated gross maxillary hypoplasia and midfacial retrusion at birth with a relative Class III malocclusion. Direct measurement of the congenital caprine skulls confirmed these findings. The incidence of midfacial growth abnormalities in these clefted animals raises questions regarding the etiopathogenesis of facial dysmorphology that is unrelated to scarring of the maxilla. This congenital cleft palate model is currently being used to explore these questions and others related to craniofacial growth and palatal function after in utero repair.

Animals↗

The fetal cleft palate: II. Scarless healing after in utero repair of a congenital model.

The role of fetal surgery in the treatment of non-life-threatening congenital anomalies remains a source of much debate. Before such undertakings can be justified, models must be established that closely resemble the respective human anomalies, and the feasibility and safety of these in utero procedures must be demonstrated. The authors recently described and characterized a congenital model of cleft palate in the goat. The present work demonstrates the methodology they developed to successfully repair these congenital cleft palates in utero, and it shows palatal healing and development after repair. A surgically created cleft model was developed for comparative purposes. Palatal shelf closure normally occurs at approximately day 38 of gestation in the caprine species. Six pregnant goats were gavaged twice daily during gestational days 32 to 41 (term, 145 days) with a plant slurry of Nicotiana glauca containing the piperidine alkaloid anabasine; the 12 fetuses had complete congenital clefts of the secondary palate. Repair of the congenital clefts was performed at 85 days of gestation using a modified von Langenbeck technique employing lateral relaxing incisions with elevation and midline approximation of full-thickness, bilateral, mucoperiosteal palatal flaps followed by single-layer closure. Six congenitally clefted fetuses underwent in utero repair, six remained as unrepaired controls. Twelve normal fetuses underwent surgical cleft creation by excision of a 20 x 3 mm full-thickness midline section of the secondary palate extending from the alveolus to the uvula, at 85 days of gestation. Six surgically clefted fetuses underwent concurrent repair of the cleft at that time; six clefted fetuses remained as unrepaired controls. At 2 weeks of age, no congenitally or surgically created clefts repaired in utero demonstrated gross or histologic evidence of scar formation. A slight indentation at the site of repair was the only remaining evidence of a cleft. At 6 months of age, normal palatal architecture, including that of mucosal, muscular, and glandular elements, was seen grossly and histologically. Cross-section through the mid-portion of the repaired congenitally clefted palates demonstrated reconstitution of a bilaminar palate, with distinct oral and nasal mucosal layers, after single-layer repair. In utero cleft palate repair is technically feasible and results in scarless healing of the mucoperiosteum and velum. The present work represents the first in utero repair of a congenital cleft palate model in any species. The use of a congenital cleft palate model that can be consistently reproduced with high predictability and little variation represents the ideal experimental situation. It provides an opportunity to manipulate specific variables, assess the influence of each change on the outcome and, subsequently, extrapolate such findings to the clinical arena with a greater degree of relevance.

Animals↗

Body mass change during altered gravity: spaceflight, centrifugation, and return to 1 G.

To assess the effect of gravity on growth, immature rats (130-200 g) were studied during chronic altered gravity exposure and while transitioning between gravity fields. Body mass gain of rats (n = 12) exposed to 14 days of microgravity (spaceflight) was evaluated and compared to mass gain of 1 G controls. Spaceflight did not affect mass gain. Six rats exposed to 1 G following spaceflight, when compared to controls, experienced a significant (0 < 0.05) post-flight mass loss over 48 h of 13 g. Over subsequent days, however, this loss was compensated for, and no difference from 1 G controls was noted after 5 days. Exposure to hypergravity (2 G) for 16 days was evaluated [(n = 6/group): Centrifuge (C); On Center Control (OCC); Centrifuge Control (CC)]. Body mass of centrifuged and OCC rats was reduced within 24 h, with OCCs regaining control mass within 13 days. The mass difference (44 g) in centrifuged animals persisted, however, with no subsequent difference in rate of mass gain between centrifuged animals and controls over Days 3-16 (3.7 +/- 0.1 vs. 3.9 +/- 0.1 g/day, respectively). Transitioning from 2 G to 1 G resulted in a mass increase within 48 hours for centrifuged animals. Over Days 3-16 at 1 G, the rate of gain for centrifuged animals continued to increase (3.1 +/- 0.1 g/day compared to 2.1 +/- 0.1 g/day for controls); differences from control, however, were still noted on Day 16. Transitioning to an increase in a gravity field causes acute losses in body mass. In hypergravity, the acute reduction in body mass persists but the rate of mass gain is normal. Animals returning to 1 G, after acute changes, adjust to attain control mass.

Adaptation, Physiological↗

Mineral distribution in rat skeletons after exposure to a microgravity model.

Exposure to space flight models induces changes in the distribution of bone mineral in the human skeleton that has the features of a gravitational gradient. Regional bone mineral measurements with dual energy x-ray absorptiometry (DEXA) in male adults exposed to head-down tilt bed rest for 30 days show non-significant decrements in the pelvis and legs with 10% increases in the head region. Horizontal bed rest for 17 weeks reveals losses of bone mineral ranging from 2.2 to 10.4% from the lumbar spine to the calcaneus and an increase of 3.4% in the skull. Investigation of this phenomena would be most definitively carried out in an animal model. One candidate is the flight simulation model in the rat which removes body weight from the hind limbs and induces a cephalad fluid shift by suspending the animal by the tail. Weanling rats exposed to this model showed bone mineral to be lower in the hind limbs and higher in the skull after 3 weeks. These findings are similar in older 200 g animals after 2 weeks tail suspension. The purpose of this study was to determine the effect of age on the distribution of skeletal mineral in this model.

Aging↗

Comparison of Plasmodium falciparum infections in Panamanian and Colombian owl monkeys.

Parameters of blood-induced infections of the Vietnam Oak Knoll, Vietnam Smith, and Uganda Palo Alto strains of Plasmodium falciparum studied in 395 Panamanian owl monkeys in this laboratory between 1976-1984 were compared with those reported from another laboratory for 665 Colombian owl monkeys, studied between 1968-1975, and, at the time, designated Aotus trivirgatus griseimembra. The virulence of these strains was less in Panamanian than in Colombian owl monkeys, as indicated by lower mortality rates of the Panamanian monkeys during the first 30 days of patency. Maximum parasitemias of the Vietnam Smith and Uganda Palo Alto strain, in Panamanian owl monkeys dying during the first 15 days of patent infection, were significantly higher than in Colombian owl monkeys. Panamanian owl monkeys that survived the primary attack had significantly higher maximum parasitemias than the surviving Colombian owl monkeys. Peak parasitemias were attained significantly earlier after patency in Panamanian than in Colombian owl monkeys, irrespective of the strain of P. falciparum. More Panamanian than Colombian owl monkeys evidenced self-limited infection after the primary attack of either the Vietnam Smith or Uganda Palo Alto strain. The duration of the primary attacks and recrudescences were significantly shorter in Panamanian than in Colombian owl monkeys. Mean peak parasitemias during recrudescence were usually higher in Panamanian owl monkeys than in Colombian monkeys. Differences of infection parameters were probably attributable, in part, to geographical origin of the two monkey hosts and parasite strains.

Animals↗

Five drug regimens for treatment of acute toxoplasmosis in squirrel monkeys.

Five drug regimens for the treatment of acute toxoplasmosis were compared in a monkey model. Systemic disease that is almost always fatal in squirrel monkeys within 7-9 days was produced by oral inoculation of a brain suspension made from mice chronically infected with the Beverly strain of Toxoplasma gondii. All untreated controls died of toxoplasmosis (6/6) while treatment gave the following results: sulfamethoxazole, 0/3; spiramycin, 5/5; clindamycin/sulfadiazine (CLD/SLD), 0/4; pyrimethamine/sulfadiazine (PYR/SLD), 0/5; trimethoprim/sulfamethoxazole (TMP/SMZ), 0/4. Three of the five monkeys treated with CLD/SLD died during or shortly after the experiment from probable CLD toxicity. Sulfonamides alone or in combination with PYR or TMP were significantly more effective than spiramycin in treating toxoplasmosis in this model. The dose regimen used in this study did not allow us to determine if the addition of PYR or TMP changed the protection of sulfa alone.

Animals↗

Diaphyseal Paget's disease: an unusual finding in the tibia.

Paget's disease may present in the tibia without involvement of either end of the bone. Such unusual diaphyseal lesions are invariably lytic and, rarely, may be multifocal. They almost always involve the anterior cortex of the bone and usually have a characteristic 'V-shaped' margin at one or both ends. Expansion of the bone is common. This unusual appearance is frequently an early manifestation of the disease under the age of 40 years. Awareness of this appearance is important in order to prevent incorrect diagnosis and unnecessary biopsy or surgery.

Adult↗

Experimental disseminated strongyloidiasis in Erythrocebus patas. I. Pathology.

Fatal disseminated disease was induced in ten patas monkeys infected with two Southeast Asian strains of Strongyloides stercoralis. While some animals died within 6 weeks after infection, others controlled their infections until placed on high doses of corticosteroids. Larvae were first noted in the stools 11-20 days after transcutaneous exposure to filariform larvae. Daily larval counts tended to increase as the infections progressed, but the number of larvae in the stool was not predictive of whether a monkey would control his infection or succumb to fatal disease. Hyperinfection was confirmed in the six monkeys in which counts were made of the adult female parasites in the duodenum at postmortem, as well as by pathologic findings in all animals. Clinical signs of disease were vague until dyspnea induced by terminal pulmonary hemorrhage occurred. Eosinophilia and/or basophilia were noted intermittently in some infections. Severe necrotizing duodenitis, colitis, and pulmonary hemorrhage were the most conspicuous postmortem findings. Hyperinfection has been predictably induced in a cercopithecoid monkey for the first time; a species which may lend itself to further investigations into the pathogenesis of disseminated strongyloidiasis .

Animals↗

Experimental disseminated strongyloidiasis in Erythrocebus patas. II. Immunology.

Parasite-specific humoral and cellular immune responses were evaluated in seven Erythrocebus patas monkeys experimentally infected with a Southeast Asian strain of Strongyloides stercoralis. Most animals developed high titers of anti-larval surface IgG antibody (as evaluated by the indirect immunofluorescence test), and all animals tested developed specific IgE antibody (as shown by the in vitro histamine release test). Modest lymphoproliferative responses to S. stercoralis antigens were demonstrated in most animals during the early phase of the infection (days 20-40), but disappeared later. Steroid treatment (prednisone, 12.5 mg/kg on alternate days) was given to three animals, but did not appear to significantly affect the immune parameters tested. The degree of the immune responses to S. stercoralis larval antigens did not correlate well with the course of the infection, and several animals died of disseminated disease in spite of demonstrable humoral and cellular responses to these antigens. We suggest therefore that other factors, such as local intestinal immune and nonimmune mechanisms may be of importance in protection against disseminated strongyloidiasis.

Animals↗

Antibody to type III group B Streptococcus in the rhesus monkey.

Susceptibility to infection due to intra-amniotic type III group B streptococcal infection was studied in 27 rhesus monkeys. Sera from mothers and their offspring were tested to determine the concentration of antibody to the native type III group B Streptococcus antigen. Among 17 controls there was a statistically significant association between the concentration of maternal antibody prior to infection and both the neonatal survival rate and survival time (P less than 0.05). Neonatal survival was decreased to less than or equal to 6 hours (P = 0.005) if the maternal antibody concentration was less than 0.5 micrograms/ml. Modified immune serum globulin was given intravenously to the mothers prior to intra-amniotic infection with (five animals) or without (five animals) neonatal modified immune serum globulin. Neither of the modified immune serum globulin groups demonstrated a significant reduction in the neonatal mortality rate; however, the addition of the modified immune serum globulin provided protection against rapid neonatal death among those animals born to mothers which had low or no detectable antibody. All maternal groups developed a significant increase in the concentration of antibody in postpartum sera. These results indicate that both naturally acquired and passive (modified immune serum globulin) antibodies to type III group B Streptococcus antigen are partially protective against intra-amniotic infection.

Animals↗

Paralysis in nude mice caused by polyomavirus-induced vertebral tumors.

Eighty-one of 95 BaLB/c nude mice infected intracranially with the LID strain of polyomavirus developed tumors of the vertebrae which compressed the spinal cord or peripheral nerves and produced paralysis. Wallerian degeneration was the only pathological alteration found in the nervous system of polyoma-infected mice. While polyomavirus was demonstrated in the brain and spinal cord by viral isolation and immunoperoxidase staining, no evidence of a primary demyelinating process was found. The disease produced in the present study is not a satisfactory animal model of progressive multifocal leukoencephalopathy.

Animals↗