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Biomedical subjects

J A Harris

Publications and source records attributed to J A Harris.

At least 73 records · Page 4Linked to original sources
PubMed1998

Biliary dyskinesia: natural history and surgical results.

Patients with biliary dyskinesia have symptoms consistent with biliary colic and an abnormal gallbladder ejection fraction (GEF) in the absence of cholelithiasis. Cholecystokinin hepatobiliary scan quantifies gallbladder function and may assist in selecting patients with acalculous biliary pain who would benefit from cholecystectomy. Seventy-eight patients with an abnormal GEF (< 35%) on cholecystokinin hepatobiliary scan without cholelithiasis were studied retrospectively. Patients were divided into groups based on diagnosis and treatment. In Group I, the patients who underwent cholecystectomy, 80 per cent (35 of 44) had complete symptomatic resolution whereas the remaining 20 per cent (9 of 44) had symptomatic improvement. Pathology reports demonstrated chronic cholecystitis in 95 per cent of specimens. Group II were patients with symptoms attributable to biliary dyskinesia, but did not undergo cholecystectomy. Persistence of symptoms was noted in 75 per cent (18 of 24) of patients whereas 25 per cent (6 of 24) had symptomatic resolution without any treatment. Group III consisted of patients with an abnormal ejection fraction who had improvement of symptoms after treatment for an alternative diagnosis (n = 10). These findings suggest that an abnormal ejection fraction does not always indicate gallbladder disease. Alternative diagnoses must be investigated and treated. Patients with persistent biliary type symptoms in combination with an abnormal GEF in the absence of other attributable causes can expect a favorable response to cholecystectomy.

Adult↗
PubMed1997

Birth prevalence, mutation rate, sex ratio, parents' age, and ethnicity in Apert syndrome.

Apert syndrome was studied to determine birth prevalence, mutation rate, sex ratio, parents' age, and ethnicity among 2,493,331 live births registered in the California Birth Defects Monitoring Program (CBDMP) from 1983 through 1993; 31 affected infants were identified. The sample was completed with an additional 22 cases from the Center for Craniofacial Anomalies (CCA), University of California, San Francisco, for a total of 53 affected children. Birth prevalence, calculated from the CBDMP subsample, was 12.4 cases per million live births (confidence interval [CI] 8.6,17.9). The calculated mutation rate was 6.2 x 10(-6) per gene per generation. Asians had the highest prevalence (22.3 per million live births; CI 7.1,61.3) and Hispanics the lowest (7.6 per million, CI 3.3-16.4). In the large population-based CBDMP subsample, there was an almost equal number of affected males and females, (sex ratio 0.94) but in the clinical CCA subsample, there were more affected females (sex ratio 0.79). For all cases, the mean age of mothers was 28.9+/-6.0 years, and of fathers was 34.1+/-6.2 years. Almost half of fathers were older than 35 years when the child was born; for more than 20% of cases, both parents were older than 35 years. These findings may support the view that point mutations appear to be more commonly associated with paternal than with maternal alleles. Representing the largest systematically ascertained population-based study of Apert syndrome to date, they provide a reliable basis for genetic counseling and decision-making, and for focused research to define the cause of this syndrome.

Acrocephalosyndactylia↗
PubMed1997

A further evaluation of the Aggression Questionnaire: issues of validity and reliability.

An analysis of the four scales from Buss and Perry's (1992, Journal of Personality and Social Psychology, 63, 452-459) Aggression Questionnaire was conducted. Examined was the internal consistency, test-retest reliability, the influence of social desirability, and the interrelationships with other measures of aggression. The results suggest that the four scales of The Aggression Questionnaire have moderate to high internal consistencies and are stable over seven months of testing. Social desirability was found to have a moderately high negative relationship with the aggression scales suggesting that social desirability may influence responses provided on The Aggression Questionnaire. In addition, the four aggression scales were found to be positively related to other measures of aggression including scales assessing affect instability and aggressive attitudes, as well as scales designed for clinical use, suggesting some degree of construct validity.

Adolescent↗
PubMed1997

Environmental predictors of personality differences: a twin and sibling study.

Nonshared environmental influences have consistently been shown to account for at least as much of the variance in personality as genetic factors, but the nature of these nonshared influences has largely remained unidentified. To identify environmental predictors of differential personality development, the Personality Research Form and 4 measures of people's perceptions of their background environments were administered to 143 adult twin pairs (93 monozygotic [MZ] and 50 dizygotic [DZ] and 66 pairs of same-sex nontwin (NT) siblings. Differences between MZ twins, DZ twins, and NT siblings in a number of dimensions of personality were significantly related to differences on the environmental measures, and phenotypic correlations between the personality and environment measures were themselves entirely attributable to correlated nonshared environmental effects.

Adult↗
PubMed1996

Chorionic villus sampling and transverse digital deficiencies: evidence for anatomic and gestational-age specificity of the digital deficiencies in two studies.

Several but not all studies indicate that chorionic villus sampling (CVS) is associated with an increased risk for transverse limb deficiencies, including digital deficiencies. It has been suggested that variations in results regarding the transverse digital deficiencies (TDDs) may be due to the use of different classification criteria. We present the combined analysis of two case-control studies, the U.S. Multistate CVS (US) study and the Italian Multicentric Birth Defects (IP-IMC) study, using two different definitions of TDDs. We compared the frequency of CVS exposure in control infants with that among those infants with any number of affected digits (any TDD), and those with all five digits of at least one limb affected (extensive TDDs). The estimated relative risk (RR) for any TDD following CVS was 10.6 (IPIMC) and 6.6 (US). For the extensive TDDs, the RR was 30.5 (IPIMC) and 10.7 (US). In both studies, extensive TDDs were less than 25% of all TDDs. Compared to all TDDs, extensive TDDs were more likely to occur after CVS performed earlier in the first trimester (before 10-11 weeks' gestation). These findings suggest a relationship between the timing of CVS and the severity of TDDs; indicate that using a restrictive definition of TDDs (all five digits affected) may limit the ability to evaluate the association between CVS and TDDs in populations in whom CVS is usually performed at or after 10 weeks' gestation; and highlight the necessity to consider gestational age in any evaluation of the relative risk for limb deficiencies associated with CVS.

Adult↗
PubMed1996

Diencephalic asymmetries.

Structural asymmetry in diencephalic regions has been reported in a number of studies since the pioneering observations by Kemali and Braitenberg, Atlas of the frog's brain. Springer Verlag: 1969. Anatomical differences between the left and right habenulae have been identified in many lower vertebrate species. While there are few reports of structural asymmetry in the dorsal thalamus, there is evidence that asymmetrical thalamofugal projections can be induced in the visual system of chicks by lateralized sensory stimulation prior to hatching. Finally, there have been consistent reports of differences between and right sides of the hypothalamus in their sensitivity to the effects of circulating gonadal hormones in rats. In most cases, these asymmetries are sex-linked and correspond to a lateralization of function. Although the significance of these diencephalic asymmetries is still enigmatic, their existence indicates that asymmetry is not a phylogenetically recent feature of the brain, and the left-right differences in the brain may be mediated by a common ontogenetic mechanism and may underlie the development of highly specialized functions.

Animals↗
PubMed1996

Upregulation of spinal glutamate receptors in chronic pain.

Recent studies indicate that glutamate binding to N-methyl-D-aspartate receptors in the spinal cord is involved in triggering the development of chronic pain However, the processes which directly underlie the increased pain remain unclear. Here we report that, following peripheral nerve injury (ligation of the sciatic nerve) in the rat, there is an increase in immunoreactive labelling of non-N-methyl-D-asparatate, AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate), glutamate receptors in the superficial laminae of the lumbar spinal cord ipsilateral to the ligation. The increase in AMPA receptor expression peaks 14 days after nerve ligation and decreases 35 days post-ligation, corresponding to the time-course of heightened sensitivity to mechanical and thermal noxious stimuli (hyperalgesia) induced by the ligation. Given evidence that AMPA receptors in the superficial laminae mediate fast nociceptive transmission in the spinal cord, our findings suggest that an upregulation of spinal AMPA receptors contributes to hyperalgesia following peripheral nerve injury.

Animals↗
PubMed1996

Midazolam impairs the acquisition of conditioned analgesia if rats are tested with an acute but not a chronic noxious stimulus.

Three experiments investigated the effects of midazolam on acquisition of fear-mediated analgesic responses in rats conditioned on the heated floor of a hot-plate apparatus. Experiment 1 demonstrated that a moderate dose (1.25 mg/kg) of midazolam administered prior to conditioning impaired acquisition of conditioned analgesia in rats retested on the heated floor 24 h later. This effect of midazolam was reversed by the benzodiazepine receptor antagonist flumazenil. In contrast, in Experiment 2, the same or higher (2.5 mg/kg) dose of midazolam did not appear to affect the acquisition of conditioned analgesia in rats tested 24 h later with a formalin-injected paw on the non-heated floor of the hot plate apparatus. By testing rats with the opioid antagonist naloxone, Experiment 3 revealed that the higher dose of midazolam did disrupt the acquisition of conditioned analgesia in rats tested with formalin, but only by preventing acquisition of an immediate but brief analgesic response that was insensitive to naloxone. Midazolam was shown to have no effect on the acquisition of the enduring naloxone-reversible analgesia. These results are discussed in terms of benzodiazepines acting within the amygdala to produce a retrieval deficit whereby fear conditioning that takes place under the influence of a benzodiazepine can only be accessed if the animal is tested in the presence of ongoing noxious stimulation.

Animals↗
PubMed1996

Descending antinociceptive mechanisms in the brainstem: their role in the animal's defensive system.

The identification of specialized mechanisms in the mammalian brainstem that function to inhibit the rostral transmission of nociceptive (pain-related) information in the spinal cord led to an explosion of research into the neuroanatomical and neurochemical substrates of these antinociceptive systems. As outlined in the present paper, most attention was directed at those mechanisms in the periaqueductal grey (PAG) and rostral ventromedial medulla (RVM). However, comparatively little attention has been paid to the functional role of these mechanisms in animal behaviour. The purpose of the present paper is to review research into the behavioural significance of those antinociceptive mechanisms in the PAG and RVM. It is concluded that these mechanisms function as part of the animal's fear or defensive system, serving to make a threatened animal insensitive to noxious stimulation and thereby allowing that animal to engage in defensive responses instead of recuperative activities. Further, it is argued that the organization of these antinociceptive circuits reflects the animal's increasing capacity for early detection of danger. Specifically, nociception itself is held to signify the presence of immediate threat, and consequently, nociceptive input directly activates antinociceptive circuits at either the spinal level (during intense noxious stimulation) or RVM (following exposure to moderate noxious stimuli). In contrast, events that are themselves innocuous but which signal threat (either learned or innate danger signals) activate fear and defensive systems in the amygdala and PAG which engage the descending antinociceptive projections in the RVM.

Aggression↗
PubMed1996

Case-control study on maternal residential proximity to high voltage power lines and congenital anomalies in France.

The literature indicates that exposure to electro-magnetic fields (EMF) may result in an increased incidence of cancer and spontaneous abortion. The aim of the present study was to determine whether living closer to high voltage power lines (HVPL) increased the risk of congenital anomalies. We studied residential exposure in any municipality in the Central-East Region of France where there was at least one residence within 500 metres of a HVPL. This was a matched case-control design. The cases consisted of all children with congenital anomalies, identified to the population-based registry in Central-East France between 1988-91. We chose two random controls, matched for birth year and municipality, for each case. For every case and control, we measured the distance from the HVPL to the maternal residence at the time of birth of the child as a surrogate for EMF exposure. Using 100 metres from an HVPL as the cut-point between exposure and non-exposure to electro-magnetic fields produced by HVPL, yielded an odds ratio of 0.95 (95% (confidence interval) CI: 0.45-2.03). Using 50 metres as the cut-point, yielded an OR of 1.25 (95% CI: 0.49-3.22). Among the 11 cases within 100 metres, there were 2 children with chromosomal anomalies, but otherwise there was no pattern in the occurrence of specific anomalies. These data indicate a lack of association between distance to HVPL and the total number of congenital anomalies. This study does not have enough statistical power to determine whether the prevalence of a specific congenital anomaly is significantly increased as a result of living near a HVPL.

Case-Control Studies↗
PubMed1996

Antimicrobial therapy of pneumonia in infants and children.

To provide optimal management for the child with community-acquired pneumonia, the clinician must take multiple factors into consideration. The etiology of pneumonia is difficult to determine and initial choice of therapy is based on the frequency of pathogens in various age groups, local antibiotic resistance patterns of the organisms, clinical presentation, and epidemiological data. Streptococcus pneumoniae and Haemophilus influenzae remain the most common bacterial pathogens outside the newborn period. Increasing numbers of multidrug-resistant strains of S pneumoniae in the United States and Europe, the decline in H influenzae type b because of current vaccination strategies, and increasing recognition of nontypeable H influenzae as etiologic agents of pneumonia have prompted reconsideration of the drug of choice. Amoxicillin and its derivatives or oral cephalosporins are the drugs of choice for initial therapy for mild to moderate disease. For severe disease or if beta-lactamase producing organisms are a concern, extended spectrum cephalosporins are indicated. Pneumococcal pneumonia unresponsive to penicillin therapy may warrant the use of extended spectrum cephalosporins or vancomycin. For older children in whom mycoplasma is a significant cause of pneumonia, the new macrolides have provided additional options for the clinician. Azithromycin and clarithromycin are efficacious, well tolerated, and require less frequent dosing intervals. The introduction of ceftriaxone, a third-generation cephalosporin with a broad spectrum of activity and prolonged half-life, allows once-a-day intramuscular therapy that can be administered on an outpatient basis. With the availability of parenteral outpatient therapy, hospital admission is no longer required for the treatment of most cases of serious community-acquired pneumonia.

Age Factors↗
PubMed1995

Myotube driven myogenic recruitment of cells during in vitro myogenesis.

Muscular dysgenesis (mdg) is a recessive lethal mutation in the mouse which drastically affects skeletal muscle development during embryonic life. Physiologically, the disease is characterized by a complete paralysis resulting from a lack of excitation-contraction coupling. Existing electrophysiological, biochemical, and genetic evidence shows that mdg/mdg mice express a basic alteration of L-type voltage-sensitive Ca2+ channels in skeletal muscle. Studies on mdg/mdg myotubes in primary culture have shown that +/+ fibroblasts or +/+ Schwann cells may fuse with them and correct their functional deficiency by genetic complementation. As the spontaneous formation of heterocaryons is thought to be an exclusive property of myoblasts, we asked whether fibroblasts may have changed their properties before fusion occurred. We used primary cells issued from sciatic nerves dissected from newborn transgenic mice carrying the pHuDes1-nls-LacZ transgene (Des-LacZ cells) as non-muscle cells. These cells were mainly fibroblasts (80%) positive for Thy1.1 and Schwann cells positive for S100. The cultures were negative for myogenic markers (desmin, troponin T), did not form myotubes long-term, and did not display significant activation of the muscle reporter gene (pHuDes1-nls-LacZ). After a few days in coculture with dysgenic or normal myotubes, the muscle reporter gene (beta-galactosidase) was detected both within dysgenic myotubes, correlating with the restoration of normal contractile activity, and normal myotubes. As well as confirming that fusion takes place, this shows that Des-LacZ cells nuclei incorporated into recipient myotubes express their own myogenic genes. Moreover, individual mononucleated Des-LacZ cells expressing beta-galactosidase were observed, indicating that myogenic genes were being expressed before fusion. This suggests a mechanism of myotube driven myogenic recruitment of cells during the in vitro myogenesis. Analysis of the distribution of the induced Des-LacZ cells (positive for beta-galactosidase) in compartmentalized muscle cocultures showed that in the presence of dysgenic myotubes, these cells were equally distributed in both myotube free and enriched areas, whereas in the presence of normal myotubes, the positive cells remained in close vicinity of the myotubes. This difference could be explained by the fact that the dysgenic phenotype might include release of the induction process from its normal controls. Our results are consistent with the idea of a transcellular mechanism triggering myogenic differentiation in non-muscle cells, and that myotubes themselves are able to drive myogenic recruitment of cells during the in vitro myogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Increased risk for transverse digital deficiency after chorionic villus sampling: results of the United States Multistate Case-Control Study, 1988-1992.

Although numerous infants have been reported with transverse limb deficiencies after their mothers had undergone chorionic villus sampling (CVS), it has been unclear whether the procedure caused these defects. We report the results of the first multistate case-control study to assess and quantify the risk for specific limb deficiencies associated with CVS. Case subjects were 131 infants with nonsyndromic limb deficiency ascertained from 7 population-based birth defect surveillance programs, and born from 1988-1992 to mothers 34 years of age or older. Control subjects were 131 infants with other birth defects. We ascertained exposure to CVS from medical records and maternal and physician questionnaires. We assessed rates and timing of exposure to CVS, and estimated relative and absolute risks for anatomic subtypes of limb deficiency. The odds ratio for all types of limb deficiency after CVS from 8-12 weeks' gestation was 1.7 (95% confidence interval, 0.4-6.3). For specific anatomic subtypes, the strongest association was for transverse digital deficiency (odds ratio = 6.4; 95% confidence interval, 1.1-38.6). The risk for transverse digital deficiency increased with earlier gestational exposure (P < 0.01 for trend). We estimated that the absolute risk for transverse digital deficiency in infants after CVS was 1 per 2,900 births (0.03%). Exposure to CVS was associated with a sixfold increase in risk for transverse digital deficiency. The causality of this association is supported by its strength, specificity, biologic plausibility, and consistency with the results of previous studies. Although some centers already inform patients about risk for limb deficiency, this study quantifies the magnitude of risk associated with CVS from 8-12 weeks' gestation.

Case-Control Studies↗
PubMed1995

Responses of neurons to extreme osmomechanical stress.

Neurons are often regarded as fragile cells, easily destroyed by mechanical and osmotic insult. The results presented here demonstrate that this perception needs revision. Using extreme osmotic swelling, we show that molluscan neurons are astonishingly robust. In distilled water, a heterogeneous population of Lymnaea stagnalis CNS neurons swelled to several times their initial volume, yet had a ST50 (survival time for 50% of cells) > 60 min. Cells that were initially bigger survived longer. On return to normal medium, survivors were able, over the next 24 hr, to rearborize. Reversible membrane capacitance changes corresponding to about 0.7 muF/cm2 of apparent surface area accompanied neuronal swelling and shrinking in hypo- and hyperosmotic solutions; reversible changes in cell surface area evidently contributed to the neurons' ability to accommodate hydrostatic pressures then recover. The reversible membrane area/capacitance changes were not dependent on extracellular Ca2+. Neurons were monitored for potassium currents during direct mechanical inflation and during osmotically driven inflation. The latter but not the former stimulus routinely elicited small potassium currents, suggesting that tension increases activate the currents only if additional disruption of the cortex has occurred. Under stress in distilled water, a third of the neurons displayed a quite unexpected behavior: prolonged writhing of peripheral regions of the soma. This suggested that a plasma membrane-linked contractile machinery (presumably actomyosin) might contribute to the neurons' mechano-osmotic robustness by restricting water influx. Consistent with this possibility, 1 mM N-ethyl-maleimide, which inhibits myosin ATPase, decreased the ST50 to 18 min, rendered the survival time independent of initial size, and abolished writhing activity. For neurons, active mechanical resistance of the submembranous cortex, along with the mechanical compliance supplied by insertion or eversion of membrane stores may account for the ability to withstand diverse mechanical stresses. Mechanical robustness such as that displayed here could be an asset during neuronal outgrowth or regeneration.

Animals↗
PubMed1995

Discrete and reversible vacuole-like dilations induced by osmomechanical perturbation of neurons.

In cultured Lymnaea stagnalis neurons, osmolarity increases (upshocks) rapidly elicited large membranous dilations that could be dislodged and pushed around inside the cell with a microprobe. Subsequent osmolarity decreases (downshocks) caused these vacuole-like dilations (VLDs) to disappear. Additional upshock/downshock perturbations resulted in repeated appearance/disappearance (formation/reversal) of VLDs at discrete sites. Confocal microscopy indicated that VLDs formed as invaginations of the substrate-adherent surface of the neuron: extracellular rhodamine-dextran entered VLDs as they formed and was expelled during reversal. Our standard VLD-inducing perturbation was: 2-4 min downshock to distilled water, upshock to normal saline. However, a wide range of other osmotic perturbations (involving osmolarities up to 3.5 x normal, perturbations with or without Ca2+, replacement of ions by sucrose) were also used. We concluded that mechanical, not chemical, aspects of the osmo-mechanical shocks drove the VLD formation and reversal dynamics and that extracellular Ca2+ was not required. Following a standard perturbation, VLDs grew from invisible to their full diameter (> 10 microns) in just over a minute. Over the next 0.5-3 hr in normal saline, neurons recovered. Recovery eliminated any visible VLDs and was accompanied by cytoplasmic turmoil around the VLDs. Recovery was prevented by cytochalasin B, brefeldin A and N-ethylmaleimide but not by nocodazole. In striking contrast, these drugs did not prevent repeated VLD formation and reversal in response to standard osmo-mechanical perturbations; VLD disappearance during reversal and during recovery are different. The osmo-mechanical changes that elicited VLDs may, in an exaggerated fashion, mimic tension changes in extending and retracting neurites. In this context we postulate: (a) the trafficking or disposition of membrane between internal stores and plasma membrane is mechanosensitive, (b) normally, this mechanosensitivity provides an "on demand" system by which neurons can accommodate stretch/release perturbations and control cell shape but, (c) given sudden extreme mechanical stimuli, it yields VLDs.

Animals↗
PubMed1995

Confirmatory factor analysis of The Aggression Questionnaire.

A confirmatory factor analysis of the factor structure of The Aggression Questionnaire created by Buss and Perry (1992) [Journal of Personality and Social Psychology, 63, 452-459] was conducted to assess whether the scale's purported 4 factors emerged. The results generally supported the 4-factor model. However, the hostility factor may be improved if 2 items pertaining to suspicion are removed from the scale. These items had relatively low loadings on that factor and decreased the hostility scale's internal reliability.

Adult↗
PubMed1995

Sleep fragmentation, and changes in locomotor activity and body temperature in trypanosome-infected rats.

The rest-activity and body temperature 24 h cycles, as well as the structure of spontaneous sleep, were studied in rats 3 weeks after infection with monomorphic Trypanosoma brucei brucei. This parasite belongs to the species of trypanosomes that causes in humans African sleeping sickness, a neuropsychiatric syndrome that involves alterations of endogenous biological rhythms. In the infected rats, entrained to a 12 h:12 h photoperiod, a considerable hypokinesia was detected during the hours of darkness. A significant oscillation of the body temperature during 24 h was lost in some infected animals. In the other infected animals, the body temperature cycle displayed a lower amplitude and a phase advance. The mean temperature was slightly higher in the infected than in control rats during the period of light. A detailed analysis of the structure of spontaneous sleep, based on daytime electroencephalographic recordings, revealed during trypanosome infection an increased relative proportion of wake, and a decreased percent value of synchronized sleep. A marked reduction of the mean REM latency and a fragmented pattern of synchronized sleep, resulting in a considerable alteration of the REM-non-REM sleep sequences, were also observed in the infected animals. These findings indicate that trypanosomiasis in the rat results in a striking sleep fragmentation, as well as in changes of locomotor activity and body temperature rhythm. Thus, trypanosome infection in the rat provides an experimental model of sleep dysregulation in a structurally intact brain, and may provide an animal model of endogenous rhythm changes documented in African sleeping sickness.

Analysis of Variance↗