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Biomedical subjects

J Harris

Publications and source records attributed to J Harris.

At least 217 records · Page 12Linked to original sources

Interaction between the caudal brainstem and the lamprey central pattern generator for locomotion.

Because of its remarkable simplicity and the robustness of the isolated preparation, the lamprey has been used as a model system to study locomotion and its central pattern generator. The function of the spinal cord is relatively well understood in this context, but the role of the brain or even the caudal brainstem remains less so. We here present a study of the interaction between the caudal brainstem and the spinal pattern generator for locomotion. We show that the interaction is highly complex, with both feedforward input from the brainstem to spinal cord and feedback input from the spinal cord to brainstem playing a significant role in the motor output during locomotion. The brainstem, when diffusely stimulated pharmacologically, can initiate fictive locomotion, or it can disrupt or alter the ongoing D-glutamate initiated motor output. The nature of the disruptions vary greatly, and can induce generalized irregularity, while the alterations can include accelerating or decelerating of the bursting. All behaviors are displayed with spectrograms of the motor nerve discharge. We also show that the unstimulated brainstem can disrupt as well as slow the bursting, but in a complex fashion. Finally, a slow episodic behavior initiated from the caudal brainstem is also described. This can be elicited either by D-glutamate to the brainstem or by ascending activity from the spinal cord pattern generator. Thus, we demonstrate that the interaction between the brainstem and the spinal cord during the production of locomotion is highly complex. The locomotion that is exhibited by the combined brainstem-spinal cord preparation is extremely variable. This is in striking contrast to the variability of the locomotor output pharmacologically induced in the spinal cord alone. The latter preparation exhibits remarkable regularity, or upon occasion, irregularity, but not the routine irregularity or the systemic up and down changes in frequency seen with the brainstem present. However, the pattern of frequency changes induced by the brainstem is not predictable, and remains to be understood.

Animals↗

Screening potential corneal donors for HIV-1 by polymerase chain reaction and a colorimetric microwell hybridization assay.

PURPOSE: Current screening of potential corneal donors for human immunodeficiency virus type 1 (HIV-1) involves serologic detection of antibodies to the virus. However, this approach cannot detect infection during the seronegative window period of the disease. We therefore evaluated the polymerase chain reaction (PCR) assay for viral nucleic acid as a possible alternative to screening cadaveric blood for HIV-1. METHODS: Blood specimens from cadavers diagnosed at autopsy with acquired immunodeficiency syndrome (AIDS) (n = 21), at high risk for HIV-1 infection (n = 47), and at no known risk (n = 350) were screened by PCR for HIV-1 proviral DNA and human leukocyte antigen (HLA)-DQ alpha sequences, and for HIV antibodies. RESULTS: All AIDS group samples were seropositive; of these, 18 (86%) and 20 (95%) of 21 were positive for HIV by PCR of proteinase K- and Chelex-extracted pellets, respectively. The seropositive samples negative by PCR testing were shown to inhibit PCR amplification. Nine (19%) of 47 high-risk specimens were HIV-positive. The no-known-risk group yielded negative results. The overall sensitivities for PCR in the proteinase K- and Chelex-treated groups were 90% and 97%, respectively, compared with Western blot reactivity. If PCR-inhibitory samples and HLA-DQ alpha-negative samples had been eliminated, sensitivity would have been 100%. Specificity was 100% for each group. CONCLUSIONS: Screening cadaveric blood by PCR may be feasible, but further refinement of the assay and blood specimen collection practices will be necessary for it to become routine. Future studies should focus on optimizing specimen procurement and preparation to reduce or eliminate specimens that inhibit PCR.

AIDS Serodiagnosis↗

The lifeline of triage.

Most acute hospitals operate a triage system to evaluate and prioritize the care and needs of clients presenting in the Emergency department. The emergency nurse, therefore, employs a variety of cognitive processes to clinically categorize clients in relation to the most acute need. This ability to clinically assess is a combination of knowledge and intuition grounded in experience and formal education. Therefore, the optimal functioning of the Emergency department is dependent upon not only the protocols and policies of hospitals, but the skills, experience and the confidence of individual triage nurses. This paper will reconsider the role of the triage nurse by addressing a literature deficit related to triage and the triage nurse, as the front line mediator, who is in the prime position of being able to rise the professional profile of the emergency nurse by making visible the care provided by nurses in this department and, most significantly, in the triage waiting room. This care extends beyond pointing to the waiting room clock and a sign which informs clients of the purposes of the emergency care department. This paper will also discuss a range of strategies used by the authors to enhance effective triaging to ensure a quality standard in client care.

Clinical Competence↗

A prospective study of anatomico-pathological changes in abdominal aortic aneurysms following endoluminal repair: is the aneurysmal process reversed?

AIM: The aim of this prospective study was to analyse early anatomico-pathological changes in abdominal aortic aneurysms (AAA) following endoluminal repair to determine if the natural history of continued expansion of AAA is reversed. MATERIALS AND METHODS: Sixty-seven of 85 patients undergoing endoluminal AAA repair between May 1992 and August 1995 had their operations prior to the end of February 1995 and were potentially available for follow up at 6 months or longer after operation. Excluded were: patients with failed endoluminal repairs (n = 14), patients who died within 6 months of operation (n = 5), patients with anastomotic AAA (n = 1), leaving 47 patients in the study group. Based on contrast enhanced CT performed preoperatively, within 10 days of operation and 6, 12 and 18 months after operation patients were divided into two groups: those in whom the AAA maximum transverse diameter (MTD) decreased Group I (n = 39) and those in which it increased Group II (n = 8). The following parameters were analysed: diameter of the supra coeliac aorta, MTD and the dimensions of the proximal and distal necks of the AAA plus extravasation ("leak") of contrast into the aneurysmal sac. RESULTS: Leak of contrast was seen in 0 of 39 patients in Gp I and 5 of 8 patients in Gp II. Patients in Group I experienced a progressive diminution in AAA mean MTD. The diameters of the proximal and distal necks increased but there was no shortening of the length of the necks in this group. In Group II the AAA MTD was dependent on whether or not the aneurysmal sac was isolated from the circulation. The diameter of the proximal and distal necks increased irrespective of this fact. CONCLUSION: We conclude that in early follow up AAA which diminish in diameter following endoluminal repair remain isolated from the general circulation. Co-incident with this decrease in AAA diameter, the proximal and distal necks increase in diameter but do not undergo any shortening in length. This paradoxical increase in neck diameter, was not progressive in the period of follow-up.

Aged↗

The descriptive epidemiology of anophthalmia and microphthalmia.

BACKGROUND: Anophthalmia and microphthalmia are serious eye malformations which recently have been associated with exposure to Benomyl. Data on these malformations are scarce in the literature and reported prevalences at birth vary strongly. METHODS: Data from three large registers of congenital malformations were analysed and comprised 849 malformed infants based on close to 5.7 million births. RESULTS: This is the largest available epidemiological study on anophthalmia and microphthalmia. The prevalence at birth was 1.50 per 10,000, varying between 0.92 and 2.29 between registers but no varying significantly between races in the California register. The variation in rates was mainly due to different inclusion of chromosomally abnormal infants (mainly trisomy 13) and of infants with microphthalmia occurring with major non-eye malformations. On the other hand, rates of anophthalmia and isolated microphthalmia were similar. Other major non-eye malformations were found in 73% of infants without a known chromosome anomaly. The malformation was bilateral in 53-60% of infants except when microphthalmia existed without any other malformations when only 27% were bilateral. Sex distribution was normal, there was a slight excess of twins, and an increased risk at high maternal age. CONCLUSIONS: In analytical studies searching for the cause of these malformations, it may be useful to restrict the analysis to infants with anophthalmia or isolated microphthalmia as the recording of such cases seems to be more reliable than of microphthalmia occurring with other malformations. The conclusions presented in the literature on the possible effect of Benomyl are partly based on data with apparent very incomplete ascertainment.

Abnormalities, Multiple↗

Spinal 5-HT-receptors and tonic modulation of transmission through a withdrawal reflex pathway in the decerebrated rabbit.

1. In decerebrated, non-spinalized rabbits, intrathecal administration of either of the selective 5-HT1A-receptor antagonists (S)WAY-100135 or WAY-100635 resulted in dose-dependent enhancement of the reflex responses of gastrocnemius motoneurones evoked by electrical stimulation of all myelinated afferents of the sural nerve. The approximate ED50 for WAY-100635 was 0.9 nmol and that for (S)WAY-100135 13 nmol. Intrathecal doses of the antagonists which caused maximal facilitation of reflexes in non-spinalized rabbits had no effect in spinalized preparations. 2. In non-spinalized animals, intravenous administration of (S)WAY-100135 was significantly less effective in enhancing reflexes than when it was given by the intrathecal route. 3. When given intrathecally, the selective 5-HT 2A/2C-receptor antagonist, ICI 170,809, produced a bellshaped dose-effect curve, augmenting reflexes at low doses (< or = 44 nmol), but reducing them at higher doses (982 nmol). Idazoxan, the selective alpha 2-adrenoceptor antagonist, was less effective in enhancing reflex responses when given intrathecally after ICI 170,809 compared to when it was given alone. Intravenous ICI 170,809 resulted only in enhancement of reflexes and the facilitatory effects of subsequent intrathecal administration of idazoxan were not compromised. 4. The selective 5-HT3-receptor blocker ondansetron faciliated gastrocnemius medialis reflex responses in a dose-related manner when given by either intrathecal or intravenous routes. This drug was slightly more potent when given i.v. and it did not alter the efficacy of subsequent intrathecal administration of idazoxan. 5. None of the antagonists had any consistent effects on arterial blood pressure or heart rate. 6. These data are consistent with the idea that, in the decrebrated rabbit, 5-HT released from descending axons has multiple roles in controlling transmission through the sural-gastrocnemius medialis reflex pathway. Thus, it appears 5-HT tonically inhibits transmission between sural nerve afferents and gastrocnemius motoneurones by an action at spinal 5-HT1A-receptors. Spinal 5-HT2A/2C-receptors may mediate a weak inhibition of transmission in the spinal cord, but more convincing evidence was obtained for their involvement in descending facilitatory tone. Further, some of the facilitatory consequences of spinal alpha 2-adrenoceptor blockade may be mediated through 5-HT2 type receptors. Spinal 5-HT3 receptors do not appear to have a major role in tonic modulation of the sural-gastrocnemius medialis reflex.

Animals↗

Would Aristotle have played Russian roulette?

This paper continues the debate between myself and Peter Singer et al started in the Journal of Medical Ethics volume 21, no 3 about the ethical respectability of the use of QALYs in health care allocation. It discusses the question of what, in the way of health care provision, would be chosen by rational egoists behind a Rawlsian "veil of ignorance", and takes forward the vexed question of what is to count as "doing good" and hence as "doing the most good" in health care. Most importantly, this paper argues that it would be unfair to discriminate against people because they have been disadvantaged by their genetic condition. It notes that McKie et al in their reply to my first contribution to this debate continue to fail to distinguish between chance and probability and it is argued that this failure causes them to miss the whole point of the argument.

Ethical Theory↗

The epidemiology of anotia and microtia.

We studied a large data set from three registries of congenital malformations (central-east France, Sweden, and California), a total of 954 cases, known chromosome anomalies excluded. The prevalence at birth varied significantly between programmes, probably to a large extent because of different ascertainment and inclusion criteria, from 0.76 per 10,000 births in the French programme to 2.35 in the Swedish. Within the California programme, there is a racial variability in prevalence with lower values among whites (and probably blacks) than in Hispanics and Asians. Also the proportion of anotia and microtia varies between races with the lowest proportion of anotia in whites. Anotia and microtia are equally often associated with other malformations and show other similar epidemiological characteristics. In unilateral cases, the right side is more frequently malformed than the left side, especially when the ear malformation is isolated. There is a male excess, most pronounced in isolated forms. Among associated malformations, facial clefts and cardiac defects are the most common ones (each about 30% of infants with associated malformations), followed by anophthalmia or microphthalmia (14%), limb reduction defects or severe renal malformations (11%), and holoprosencephaly (7%). There is a maternal parity effect seen, an increased risk at parity 4+ (standardised for maternal age), more pronounced for anotia than microtia.

Abnormalities, Multiple↗

Clinical and neuropsychological comparison of psychotic depression with nonpsychotic depression and schizophrenia.

OBJECTIVE: This study compared the clinical and neuropsychological characteristics of patients with psychotic depression to those of patients with nonpsychotic depression and patients with schizophrenia. METHOD: Two hundred eighteen patients over the age of 45, including 30 who met the DSM-III-R criteria for unipolar major depression with psychotic features, 28 with nonpsychotic unipolar major depression, and 160 with schizophrenia, were examined. Subjects were evaluated on several clinical measures as well as on neuropsychological tests of attention, learning, memory (retention), psychomotor speed, and motor skills. RESULTS: The three groups were comparable in age and education. The severity of depressive symptoms in the depressed patients with and without psychosis was similar. The patients with psychotic depression were comparable to those with schizophrenia on the neuropsychological measures; they were more impaired than the patients with nonpsychotic depression on the measures of psychomotor speed, motor skills, attention, and learning. The cognitive deficits seemed to be trait-related. CONCLUSIONS: The findings provide additional support for the validity of psychotic depression as a diagnostic category distinct from nonpsychotic depression.

Age of Onset↗

Neuronal cell migration in C. elegans: regulation of Hox gene expression and cell position.

In C. elegans, the Hox gene mab-5, which specifies the fates of cells in the posterior body region, has been shown to direct the migrations of certain cells within its domain of function. mab-5 expression switches on in the neuroblast QL as it migrates into the posterior body region. mab-5 activity is then required for the descendants of QL to migrate to posterior rather than anterior positions. What information activates Hox gene expression during this cell migration? How are these cells subsequently guided to their final positions? We address these questions by describing four genes, egl-20, mig-14, mig-1 and lin-17, that are required to activate expression of mab-5 during migration of the QL neuroblast. We find that two of these genes, egl-20 and mig-14, also act in a mab-5-independent way to determine the final stopping points of the migrating Q descendants. The Q descendants do not migrate toward any obvious physical targets in wild-type or mutant animals. Therefore, these genes appear to be part of a system that positions the migrating Q descendants along the anteroposterior axis.

Animals↗

Adenosine receptor blockade and hypoxia-tolerance in rainbow trout and Pacific hagfish. I. Effects on anaerobic metabolism

The physiological properties of adenosine may be essential in the control of energy metabolism for the survival of animals exposed to oxygen shortages. Accordingly, we tested the hypothesis that adenosine modulates metabolic regulation in rainbow trout and Pacific hagfish exposed to acute hypoxia. Treatment of hypoxic rainbow trout (PwO2=3.33 or 4.00 kPa) with the adenosine receptor (AR) blocker theophylline was associated with greater increases in plasma [lactate], more rapid and pronounced metabolic acidosis, higher tissue [lactate], and lower heart creatine charge and glycogen content than in the hypoxic controls. The recruitment of anaerobic metabolism in hypoxic trout treated with enprofylline, an AR blocker with very weak affinity, was intermediate to that of the hypoxic theophylline-injected and control groups. In hagfish, plasma [lactate] increased following exposure to a PwO2 of 1.33 kPa but did not increase following exposure to 3.33 kPa and, like plasma acidosis, it was greatest in the animals treated with theophylline. These findings indicate that AR blockade results in a more rapid and pronounced recruitment of anaerobic metabolism following acute hypoxic exposure, and while rainbow trout and Pacific hagfish show marked differences in their responses to hypoxia, adenosine appears to play an important protective role in both species.

Journal Article↗

The aging eye: pathophysiology and management.

As humans go through the normal process of aging, there is drooping of many of the deep structures of the eyes. For generations, and continuing today, aesthetic plastic surgeons are removing superficial structures (i.e., skin and fat) as the primary management of drooping upper and lower eyelids. However, the dissatisfaction of patients with the results of these conventional approaches (Fig. 1) has led to further research and the development of innovative techniques that give a more youthful and harmonious appearance to the face.

Journal Article↗

Consumer health information demand and delivery: implications for libraries.

Consumers are increasingly interested in information that will help them manage their own health and that of their families. Managed care and other health providers see consumer health information as one tool to help improve patient satisfaction and reduce costs. There is a huge and varied supply of such information, provided through myriad sources. This article summarizes findings from a preliminary assessment of consumer health information demand and delivery supported by the U.S. Department of Health and Human Services. It highlights patterns of consumer interest and supply sources, identifies problems that confront those looking for information, and suggests a role for libraries as providers and interpreters of health information. The last publicly released general study on consumer health information was commissioned by General Mills in 1979. In the sixteen years since then, the scope of consumer health information has become huge and diverse; with increased responsibility for health, consumers have developed both broad interests and very specific needs. The Department of Health and Human Services commissioned a preliminary assessment of consumer health information demand and delivery to lay the foundation for a more comprehensive understanding of the issues. This article highlights some of the key findings that suggest a role for libraries as consumer health information providers and interpreters.

Adult↗

A simple and sensitive microtiter plate estrogen bioassay based on stimulation of alkaline phosphatase in an endometrial adenocarcinoma cell line (Ishikawa line).

We have developed an estrogen bioassay using the Ishikawa human endometrial adenocarcinoma cell line grown in 96-well microtiter plates. Alkaline phosphatase enzyme activity (Alkp) in these cells was markedly stimulated by estrogen (E2), and this enzyme can be easily quantified in situ using a chromogenic substrate. Estradiol induces AlkP at levels as low as 10-8M. The induction of AlkP is specific for estrogens as for other steroids and other steroidal materials (Progesterone, Tamoxifen, clomiphene citrate, Ru 486, ICI) could not produce a similar effect. The stimulation of AlkP in Ishikawa cells is not only specific for estrogen, it is highly reproducible and sensitive and permits large numbers of samples to be assayed with ease. The non-radioactive nature of the assay makes it attractive to developing countries.

Adenocarcinoma↗

Is there a moral obligation not to infect others?

The emergence of HIV infection and AIDS has refocused concern on the obligations surrounding the carrying and transmission of communicable diseases. This article asks three related questions: Is there a general duty not to spread contagion? Are there special obligations not to communicate disease in the workplace? And does the mode of transmission of the disease affect the ethics of transmission and, if so, how and to what extent? There seems to be a strong prima facie obligation not to harm others by making them ill where this is avoidable, and this obligation not to communicate disease applies as much to relatively trivial diseases like the common cold as it does to HIV disease. The reasonableness of expecting people to live up to this obligation, however, depends on society reciprocating the obligation in the form of providing protection and compensation.

Communicable Diseases↗

The content of glutathione and glutathione S-transferases and the glutathione peroxidase activity in rat liver nuclei determined by a non-aqueous technique of cell fractionation.

Hepatocellular nuclei require glutathione, glutathione S-transferases (GSTs) and Se-dependent glutathione peroxidase (GPx) for intranuclear protection against damage from electrophiles or products of active oxygen. Data so far available from the literature on nuclei isolated in aqueous systems range from glutathione, GSTs and GPx either being absent altogether to being present in quantities in excess of those in the cytoplasm. This paper describes a small-scale preparation of a nuclear fraction from rat liver by a non-aqueous technique, designed to retain nuclear water-soluble molecules in situ, since low-molecular-mass compounds can diffuse freely into other compartments during aqueous separation. This non-aqueous procedure shows the nucleus to contain glutathione at 8.4 mM and soluble GSTs at 38 micrograms/mg of protein, the enrichment over the homogenate being 1.2-1.4-fold. Se-dependent GPx activity was also present in the nucleus (56 m-units/mg), although with slightly lower activity than in the homogenate (0.7-fold).

Animals↗

Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis.

The neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders with an autosomal-recessive pattern of inheritance. There are 3 main categories of childhood NCL, namely, infantile, late-infantile, and juvenile NCL. These can be distinguished on the basis of age of onset, clinical course, and histopathology. A number of variant forms of NCL have also been described, and these show symptoms intermediary between the main classical forms. The genes for both the infantile and juvenile forms of NCL have previously been mapped to chromosome areas 1p32 and 16p12, respectively. The gene for late-infantile NCL (LINCL), CLN2, has been excluded from both these loci, but its location is as yet unknown. Recently, CLN5, the gene for the Finnish variant form of LINCL, was mapped to 13q21.1-32. Using the 3 microsatellite markers which were most tightly linked to CLN5, we have excluded CLN2 from this region using a subset of 17 families. Thus, CLN2 represents a fourth distinct genetic locus involved in the pathogenesis of NCL.

Age of Onset↗