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Biomedical subjects

J A Harris

Publications and source records attributed to J A Harris.

At least 91 records · Page 5Linked to original sources

Effects of benzodiazepine microinjection into the amygdala or periaqueductal gray on the expression of conditioned fear and hypoalgesia in rats.

Four experiments studied the effects of an intracranial microinjection of a benzodiazepine (midazolam) on the expression of conditioned fear (measured as passive avoidance) and conditioned hypoalgesia in rats. Unilateral microinjection of midazolam into the basolateral amygdala reduced both hypoalgesic and avoidance responses, whereas unilateral microinjection of midazolam into the ventrolateral region of the periaqueductal gray (vlPAG) reduced the hypoalgesic response but not the avoidance response. The results are discussed in terms of gamma-aminobutyric acid-ergic inhibition of antinociceptive mechanisms in the vlPAG and of the activation of these mechanisms by amygdala-based fear processes.

Amygdala↗

Fos expression in the spinal cord is suppressed in rats displaying conditioned hypoalgesia.

Two experiments used c-fos expression as a marker of spinal nociceptive processing to study the neural correlates of hypoalgesic responses to conditioned stimuli (CSs) paired with an aversive event. Immunoreactive (ir) neuronal labeling of Fos, the nuclear protein encoded by the c-fos gene, was examined in the spinal cords of rats killed 2 hr after injection of dilute formalin into a hind paw. Compared with control rats either not conditioned or conditioned in one environment but tested elsewhere, there were significantly fewer Fos-ir neurons in the spinal cords of rats displaying hypoalgesic responses when tested in the presence of aversive CSs. Naloxone abolished hypoalgesic responses and reinstated spinal Fos expression, indicating that aversive CSs activated opioid-based antinociceptive mechanisms. The results confirm that aversive CSs produce hypoalgesia by inhibiting the transmission of ascending nociceptive information.

Animals↗

Periconceptional vitamin use, dietary folate, and the occurrence of neural tube defects.

With a case-control study, we investigated whether periconceptional intake of supplemental or dietary folate reduced the risk of having a neural tube defect (NTD)-affected pregnancy. Mothers of 549 (88% of eligible) cases and 540 (88%) controls were interviewed in person about vitamin supplements used in either the 3 months before or the 3 months after conception and also about usual diet in the 3 months before conception. Women with any use of a folic acid-containing vitamin in the 3 months before conception had a lower risk of having an NTD-affected pregnancy [odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45-0.94]. ORs were similar for 3 levels (< 0.4, 0.4-0.9, and > 0.9 mg per day) of average daily intake of folic acid. Any level of use in the first 3 months after conception resulted in a lowered risk as well (OR = 0.60; 95% CI = 0.46-0.79). Reduced risks were less marked for Hispanics and were not observed among women who graduated from college. Modest reduced risks were noted among non-vitamin users whose estimated daily dietary intake of folate was more than 0.227 mg. We observed decreasing risk with increasing folate intake from combined dietary sources and vitamin supplements. A reduction in NTD risk associated with folate intake is consistent with other studies; however, the reduced risk may be particular to subsets of the population, primarily non-Hispanic women and women whose education does not exceed high school.

Adult↗

Closed drainage versus open packing of infected pancreatic necrosis.

Infected pancreatic necrosis is the most lethal form of pancreatic infections. We have compared our results of open packing and closed catheter drainage after surgical debridement in 20 patients between 1978 and 1993. There were 18 men and 2 women, ages 18 to 72 (mean 54 years). Pancreatitis was attributed to alcohol in eight patients, gallstones in four, surgery in four, hyperlipidemia in one, and was unknown in one. The most common infectious organisms were Strep. viridans, E. coli, Staph aureus, and Candida albicans. Surgical debridement and closed catheter drainage without lavage was the initial treatment in nine patients. Seven of 9 (78%) required reoperation for recurrent abscess and necrosis. Procedure related morbidity was 70 per cent and overall mortality was 44 per cent. Sepsis was the cause of death in three patients and multi-system organ failure in one patient. Surgical debridement and open packing was performed in 11 patients. Each patient had scheduled reoperations for repeat debridement and packing an average of 10 times over 21 days. Procedure-related morbidity was 73 per cent and overall mortality was 18 per cent. One patient died of cardiac failure and one of multisystem organ failure. Retroperitoneal hemorrhage and recurrent abscesses were more frequent after closed drainage, whereas gastric fistula and incisional hernia were more frequent after open packing. Ventilator dependence, pancreatic and intestinal fistula, and organ failure occurred at the same rate. In conclusion, surgical debridement and open packing, with planned redebridement and packing, is more effective in controlling the septic process than is closed catheter drainage of infected pancreatic necrosis.

Abscess↗

Hemodynamic sequelae of combined arteriovenous injury in an experimental canine hindlimb model: venous ligation vs. repair.

The hemodynamic effects of combined venoarterial injury and stasis were studied in the hindlimbs of 10 dogs. Femoral arterial blood flow and pressure, peripheral venous pressure, and peripheral resistance were measured after the restoration of blood flow following venoarterial injury and a 4-hour period of occlusion for up to 72 hours. In one limb of each animal both the artery and vein were repaired, whereas only the artery was repaired in the other limb and the vein was ligated. Arterial blood flow was similar in both groups but was significantly diminished from baseline for the first 30 minutes after restoration of blood flow, but then it became significantly reduced in the limbs with venous ligation when compared with values in those with venous repair. By 72 hours the flow on both sides returned to control values. Peripheral venous hypertension and edema occurred in all 10 limbs with venous ligation and persisted for the 72-hour experimental period. In the 10 limbs with venous repair, edema occurred in four and venous hypertension in none. The peripheral resistance was elevated on both sides; this elevation persisted for 75 minutes and then dropped to control values. None of the repaired arteries and only one repaired vein thrombosed during the experiment. Combined venous and arterial occlusion for 4 hours reduced both the amount of arterial flow and its subsequent rate of increase compared with changes seen after release of an acute venous occlusion. The rate of increase was enhanced by repair of the affected venous segment compared with simple venous ligation.

Animals↗

Effects of midazolam and naloxone in rats tested for sensitivity/reactivity to formalin pain in a familiar, novel or aversively conditioned environment.

Rats tested for sensitivity/reactivity to formalin-induced pain in either an aversively conditioned or a novel environment displayed immediate but transient hypoalgesic responses that were insensitive to either a benzodiazepine (midazolam) or an opioid antagonist (naloxone). Exposure to the aversively conditioned, but not to the novel environment also provoked a more enduring hypoalgesic response that was abolished by either midazolam or naloxone. The results were taken to mean that fear is sufficient but not necessary for the production of hypoalgesic responses to environmental stimuli.

Analgesia↗

Penetrating atherosclerotic ulcers of the aorta.

PURPOSE: This study investigates the natural history and optimal imaging modality of penetrating atherosclerotic ulcers of the aorta. METHODS: We reviewed our experience with 29 penetrating ulcers in 18 patients. Computed tomography (17 patients), magnetic resonance imaging (nine patients), and aortography (five patients) were used for diagnosis and follow-up. Patients were typically elderly (average age 74 years) and had hypertension and coronary artery disease. Ulcers were most common in the distal descending thoracic aorta (31%) and were characterized by a discrete ulcer crater (100%) and thickened aortic wall (89%). Modes of presentation included chest or back pain in four patients, distal embolization in two patients, and abnormal chest radiography results in one; the remaining were incidental findings. RESULTS: Follow-up was available in ten patients with 17 ulcers from 1 to 7 years. Recurrent pain occurred in two patients, recurrent embolization occurred in one patient, and seven patients remained symptom free. Progression to saccular pseudoaneurysm occurred in five ulcers, and fusiform aneurysm occurred in two ulcers. Two ulcers were associated with an increase in aortic diameter, and nine ulcers did not change. There were no cases of aortic dissection or rupture in the follow-up period. There were no deaths and only one patient underwent resection. CONCLUSION: The natural history of penetrating atherosclerotic ulcers is one of progressive aortic enlargement, with saccular and fusiform aneurysms the result if follow-up is sufficient. Aortic dissection, aortic rupture, and embolization can also occur but are less common. Contrast-enhanced computed tomography is the primary imaging modality.

Aged↗

Low and high doses of midazolam differentially affect hypoalgesia in rats conditioned to a heat stressor.

These experiments examined the effects of a benzodiazepine (midazolam) on rats' sensitivity-reactivity to the heated floor of a hot-plate apparatus. Rats were either previously exposed to the heated floor, or naive to the hot-plate apparatus, while control rats were familiarized with the apparatus in the absence of pain. A low dose (0.63 or 1.25 mg/kg) of midazolam attenuated the conditioned hypoalgesic response resulting from pre-exposure to a heated floor, but did not affect the hypoalgesic response elicited by exposure to a novel hot-plate apparatus nor the "baseline" sensitivity-reactivity among control rats. A high dose (2.5 mg/kg) of midazolam resulted in a naloxone-insensitive increase in both the conditioned and the novelty-induced hypoalgesia, and provoked a small, but naloxone-reversible increase in paw-lick latencies among control rats. The results were taken to mean that exposure to the heated floor results in hypoalgesic responses as a consequence of fear conditioning and the reinstatement of novelty. Midazolam was assumed to attenuate conditioned hypoalgesia by reducing fear but at the high dose to augment the hypoalgesic effects of novelty.

Analgesia↗

Effects of an infusion of morphine into the accumbens nucleus upon acquisition of hypoalgesic and fear responses in rats exposed to a heart stressor.

Four experiments examined the effects of an infusion of morphine into the accumbens nucleus upon the aversive conditioning that can occur in rats exposed to the heated floor of a hot-plate apparatus. An infusion of morphine into the accumbens nucleus but not into the caudoputamen or into the prefrontal cortex impaired the acquisition of a conditioned hypoalgesic (Experiment 1) and fear (Experiment 4) response. This impairment was dose-dependent (Experiment 2) and mediated by opioid receptors in the accumbens nucleus, because it was removed by a systemic (Experiment 3a) or by an accumbal (Experiment 3b) infusion of naloxone. The results were attributed to an antagonism between the reinforcement process for aversive conditioning and the appetitive properties of an accumbal infusion of morphine.

Analgesia↗

Adverse pregnancy outcomes in relation to water consumption: a re-analysis of data from the original Santa Clara County Study, California, 1980-1981.

Residents of a census tract that received drinking water from a well contaminated with solvents were previously shown to experience a spontaneous abortion rate over twice that occurring in an unexposed census tract. In addition, the rate of birth defects in the exposed tract was three times that in the unexposed tract. Surprisingly, increased tapwater consumption was associated with higher rates of spontaneous abortions in both the exposed and the unexposed tracts. Subsequent studies in this area have investigated the relation between spontaneous abortions and consumption of tapwater in more detail. In this report, data from the original study have been re-analyzed using methods comparable with those used in more recent studies. These results confirm the association between spontaneous abortions and reported cold tapwater consumption that was seen in the original study. The observed effect was not due to maternal risk factors, nor was it a function of consumption of bottled water. After controlling for bottled water, the odds ratio for consumption of tapwater was 3.4 (95% confidence interval = 0.6-19.4).

Abortion, Spontaneous↗

Polymerase chain reaction in detecting HIV infection among seropositive infants: relation to clinical status and age and to results of other assays.

The polymerase chain reaction (PCR) for human immunodeficiency virus (HIV) was evaluated using coded blood specimens from infants whose clinical status is now known. A micromethod for the efficient isolation of mononuclear cells from small volumes of blood, and definitions of PCR positivity that took into account the number and purity of these mononuclear cells, were established in an attempt to define parameters for quality assurance. Results of HIV culture, p-24 antigen, and HIV-specific IgA obtained on the same specimens were compared to PCR results. PCR had a specificity of 100% among 83 specimens from 50 babies known to be uninfected. Sensitivity among 26 HIV-infected infants older than 3 months was 98% (44 of 45 specimens); the one negative specimen, which had also been culture negative, gave a positive PCR result on the remaining aliquot when tested after decoding. Among infected infants less than 3 months old, which is an age when diagnosis by other assays is most problematic, PCR identified 10 of 10 patients (10 of 11 specimens) including two younger than one month. Viral culture showed the best concordance with PCR; however, in three infants, positive PCR results were observed several months before positive results were observed by viral culture.

Aging↗

Psychosocial effects of juvenile rheumatic disease. The family and peer systems as a context for coping.

The psychosocial effects of juvenile rheumatic diseases and disease activity were examined among 24 children and their families (12 children with a rheumatic disease and 12 children with no chronic illness). Each child with rheumatic illness was paired with a healthy control child nominated by their classroom teacher. Family and child functioning was assessed through measures of competence, coping, and adjustment and through direct observation of social functioning with peers at school. Multivariate and univariate analyses were performed to examine scores on the assessment measures, percentages of time spent in peer activities, and frequency scores for types of peer interactions. The results of these analyses indicated that juvenile rheumatic disease (JRD) is not associated with detrimental psychosocial outcomes. Instead, the results indicated that JRD children and their families actively utilize multiple coping strategies. These findings stress the importance of including and examining the family and peer systems as contexts for coping in future research.

Adaptation, Psychological↗

Bias in congenital malformations information from the birth certificate.

An analysis of 1983 data from California birth certificates, and from the California Birth Defects Monitoring Program case registry, showed that there is a bias in reporting of congenital malformations on the birth certificate. Hospitals with many births erroneously report lower malformation rates than do hospitals with few births. The bias is partly due to the source of information; larger hospitals are more likely to get their information about malformations from the obstetrician than from the pediatrician. Since malformation data recorded on the birth certificate is both incomplete and biased, at present it is advisable to use these data for epidemiologic analyses with great caution.

Bias↗

Repeated episodes of C5a-induced neutrophil influx do not result in pulmonary fibrosis.

Multiple reactive oxygen species-induced epithelial injury by glucose, glucose oxidase, and lactoperoxidase instillation in the lung results in a progressive interstitial fibrosis. To test the hypothesis that multiple pulmonary inflammatory responses alone would not result in fibrosis, three sequential inflammatory reactions were produced at weekly intervals in hamster lungs via intratracheal instillation of human recombinant C5a. Numbers of neutrophils and total inflammatory cells in bronchoalveolar lavage (BALF) increased significantly at 24 h after each C5a treatment compared with saline controls. Neutrophils increased by 3-, 33-, and 34-fold compared with the corresponding controls at 24 h after the first, second, and third doses, respectively, but returned to control levels by six days postinstillation. LTB4 levels increased by 24% and 20% compared with the corresponding controls at 24 h after the first and second doses but were not different from controls at other times. Hydroxyproline levels in treated animals did not differ significantly from control levels throughout the study. Protein levels were significantly increased at 24 h after the second and third doses and six days after the third dose compared with the corresponding controls. Occasional foci of neutrophils in alveolar spaces were observed at 24 h after each dose, but they decreased in frequency after six days. No foci of neutrophils were observed six days after the final dose, although some epithelial degeneration was observed by transmission electron microscopy. Our results indicate that pulmonary inflammation resulting from repeated influx of neutrophils in response to multiple instillations of C5a in the lung does not cause sufficient injury to result in pulmonary fibrosis.

Animals↗

Birth defects monitoring in California: a resource for epidemiological research.

The California Birth Defects Monitoring Program maintains a population-based birth defects registry of structural congenital malformations, monitoring over 600,000 resident births annually. Cases are actively ascertained from hospitals and genetic centres throughout California and from selected facilities in adjacent states. Field staff identify presumptive cases from careful review of medical records. Diagnostic and demographic information is collected from in-patient and genetic centre medical charts for children diagnosed with major structural malformations between conception and 1 year of age. The application of these data to epidemiological investigations of birth defects is described in the context of prevalence studies, aetiological studies and evaluative studies, and the strengths and limitations of the registry data are discussed.

California↗

Early diagnosis of HIV infection in infants by detection of IgA HIV antibodies.

With the aim of achieving earlier diagnosis of human, immunodeficiency virus (HIV) infection in infants, IgA and IgM HIV antibodies in serum samples from babies born to seropositive mothers were assayed by immunoblot and enzyme-linked immunosorbent assay after removal of IgG with recombinant protein G. 64 samples were from 38 HIV-infected babies with Centers for Disease Control classifications of P1 or P2. Among these infected children IgA HIV antibodies were present in all 23 samples from those older than 12 months, in 12 of 18 samples from babies aged 6-12 months, in 5 of 10 samples from babies aged 3-5 months, and in 2 of 13 from babies under 3 months old. The 6 IgA-negative samples from infants over 6 months were all from infants with severe AIDS and/or hypogammaglobulinaemia. IgA HIV antibodies were present in twice as many samples as IgM HIV antibodies (66% vs 33%). No IgM or IgA HIV antibodies were detected in infants who subsequently seroreverted or in infants born to seronegative mothers. The correlation of the serological results with clinical information on each child suggests that detection of IgA HIV antibodies is an effective method for early diagnosis of HIV-infected infants without signs of infection.

AIDS Serodiagnosis↗