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Biomedical subjects

M Richards

Publications and source records attributed to M Richards.

At least 163 records · Page 9Linked to original sources

Neurologic and neuropsychological manifestations of human immunodeficiency virus infection in intravenous drug users without acquired immunodeficiency syndrome. Relationship to head injury.

We examined 99 human immunodeficiency virus (HIV)-negative and 122 HIV-positive intravenous drug users (IVDUs) without acquired immunodeficiency syndrome (AIDS) to determine whether HIV-positive IVDUs had more neurologic and neuropsychological impairment than their HIV-negative counterparts. Controlling for age, education, drug use, history of head injury, and interactions between head injury and HIV status and drug use, HIV-positive subjects had more extrapyramidal signs and frontal release signs. These findings persisted when asymptomatic HIV-positive subjects without systemic signs of infection and HIV-negative subjects were compared. Neurologic findings were more severe in those with more systemic illness. Among those reporting a history of head injury with loss of consciousness, neuropsychological performance was significantly worse in the HIV-positive subjects, and this increased with severity of illness. This was not true in the group without head injury, suggesting an interaction between history of head injury and the seropositive state. No relationship was noted between head injury and either drug use or HIV state. Therefore, subtle neurologic and neuropsychological abnormalities may precede clinical evidence of AIDS in IVDUs and may be more evident in those with head injury.

Adult↗

The stability of neuropsychological test performance in a group of parenteral drug users.

The stability of neuropsychological performance in a sample of drug abusers was investigated for a wide range of neuropsychological tests, using a test-retest paradigm with 16 parenteral drug users. The battery administered included tests of general intellectual function, abstract reasoning, verbal memory, language, attention, visuospatial ability, set switching, speeded performance, and manipulative dexterity. Stability coefficients were of a moderate to high magnitude for most of the tests and were comparable to coefficients found in other studies of non-drug-users. Two exceptions, however, were the Selective Reminding Test and the Perdue Pegboard. Possible reasons for instability with these two tests are discussed. It is concluded that neuropsychological investigations of drug abusers can yield consistent and reliable data, although further studies should employ alternative and/or supplementary measures of verbal memory and motor function.

Adult↗

Functional hemispherectomy.

Complete hemispherectomies were performed throughout the 1950's and early 1960's for the treatment of medically refractory seizures associated with hemiplegia. In 1964 a study published by Laine, Pruvet and Ossen reported a late post operative complication; superficial cerebral hemosiderosis. This, with its associated neurological deterioration, hydrocephalus, and at times death, led to disfavor with the procedure. It was replaced by the subtotal hemispherectomy which effectively eliminated the late complication of superficial cerebral hemosiderosis but was less successful in controlling seizures. Results decreased from 85% showing improved seizure tendency to 68%. Dissatisfied with these results, a hybrid operation was designed by Dr. Rasmussen and Dr. Villemure known as functional hemispherectomy. Removing less cortical tissue but disconnecting the remaining tissue provided a functionally complete but anatomically incomplete removal. Patients, having undergone this surgery, have obtained the same degree of seizure reduction without any of the late complications of the complete hemispherectomy. Our presentation will discuss the preoperative, operative and post-operative course of these patients. Criteria for surgery will be reviewed. A description of the surgical procedure will be included so that one can understand why the complications of aseptic meningitis, hydrocephalus, cerebral hemosiderosis and altered motor function will or will not occur postoperatively. Concerns of family and patient will be addressed throughout the presentation.

Cerebral Cortex↗

Assay of endopeptidase-24.11 activity in plasma applied to in vivo studies of endopeptidase inhibitors.

We developed a fluorometric assay for endopeptidase-24.11 (EC 3.4.24.11) in human plasma. Substrate [glutaryl-Ala-Ala-Phe-amidomethylcoumarin(AMC)] was incubated with plasma (20 microL, 30 min, pH 7.6) with (control) or without the endopeptidase-24.11 inhibitor phosphoramidon. Further incubation with aminopeptidase M released free AMC. Within-assay CVs were 4.5% and 8.6%, respectively, at 3.31 and 0.27 nmol of AMC released per milliliter per minute. The between-assay CV was 10.4% at 0.31 nmol/mL per minute and the detection limit was 0.05 nmol/mL per minute. A highly skewed distribution of endopeptidase-24.11 in 41 normal samples was found, ranging from 0.12 to 6.84 nmol/mL per minute (median = 0.44). Mean endopeptidase-24.11 concentrations were significantly higher in hypertensive subjects (0.68 nmol/mL per minute) than in normotensive subjects (0.34 nmol/mL per minute; P less than 0.05). Compared with placebo administration, the oral endopeptidase-24.11 inhibitor UK 79300 significantly inhibited the plasma enzyme at doses of 100 mg (twice daily). Although in normotensive subjects the enzyme was unaffected with doses of 25 mg, the same dose (25 mg) inhibited the plasma enzyme in hypertensive subjects. No activity was detected in sheep plasma, but addition of exogenous endopeptidase-24.11 to sheep plasma in vitro allowed in vivo assessment of the effect of infused endopeptidase-24.11 inhibitor SCH 39370.

Amino Acid Sequence↗

Interrater reliability of extrapyramidal signs in a group assessed for dementia.

Extrapyramidal signs were rated by three neurologists in 20 patients who had either been diagnosed as having probable Alzheimer's disease or who were being evaluated for dementia. In general, good interrater reliability was found for the presence or absence of extrapyramidal signs, although agreement over the presence of some signs was reduced when distinctions between normality and slight departures from normality were required.

Aged↗

Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection. III. Neurologic and neuropsychological findings.

We explored the possibility that neurologic and neuropsychological changes constitute the earliest detectable manifestations of human immunodeficiency virus (HIV) infection. Without knowledge of HIV status, we assessed neurologic signs and symptoms and administered a battery of neuropsychological tests to 208 homosexual men, of whom 84 were HIV negative, 49 were HIV positive and asymptomatic, 29 were mildly symptomatic, and 46 had significant medical symptoms but not the acquired immunodeficiency syndrome. There was no difference between the HIV-negative and HIV-positive men in the frequency of neurologic signs or of defective or borderline performance on any neuropsychological test. However, HIV-positive men performed slightly but significantly worse than HIV-negative men on tests of verbal memory, executive function, and language. Similar results were obtained when comparisons were limited to HIV-positive medically asymptomatic and HIV-negative men. There was no degradation of neurologic status or neuropsychological performance across stages of HIV severity, but neurologic and neuropsychological summary scores correlated with CD4/CD8 ratios in the HIV-positive group. Ratings of neurologic signs and symptoms correlated with neuropsychological summary scores in the HIV-positive group only. Cognitive complaints were more frequent in the HIV-positive men; they correlated with actual test performance in the HIV-positive but not HIV-negative men. The constellation of subjective and objective neuropsychological and neurologic findings suggests the possibility of a definable syndrome associated with HIV infection in asymptomatic individuals.

Adolescent↗

Evaluation of polyphosphates and polyphosphonates as degradable biomaterials.

A series of polymers, bisphenol A-based poly(phosphoesters), were evaluated as degradable biomaterials. Degradation was observed for the four polymers studied under both in vitro and in vivo conditions. The rate of degradation was affected by polymer side-chain structure and correlated with the swelling behavior. The ethyl side-chain polymers absorbed more water than their phenyl counterparts. Among the sterilization methods, UV irradiation followed by antibiotic treatment was the most suitable, as steam autoclave and ethylene oxide treatments altered the properties of several of the poly (phosphoesters). Tissue response to the poly(phosphoesters) in rabbits was characterized by minor encapsulation and slight or no lymphocyte, giant cell, or macrophage activity. No evidence of edema or necrosis was found. The elastic moduli of these materials varied from 488 MPa for poly(bisphenol A-ethylphosphate) (BPA/EOP) to 627 MPa for the more rigid poly(bisphenol A-phenylphosphonate) (BPA/PP). The ultimate strength, modulus, and energy to failure of BPA/PP were lower than those of similarly compression molded high-molecular-weight poly(L-lactic acid) (PLLA).

Animals↗

Serum corticosterone concentrations in developing shell-less and shelled turkey embryos.

1. Turkey embryos grown in shell-less culture (EO) display normal development to day 14 of incubation, after which growth rate is reduced and mortality increases, compared to age-matched in ovo (IO) embryos (Richards 1982. Long term shell-less culture of turkey embryos. Poultry Sci. 61, 2089-2096). 2. In this study serum corticosterone concentrations were monitored in normally incubated embryos and embryos maintained in shell-less culture. 3. On days 14 and 16 of incubation, corticosterone levels were greater (P less than 0.05) in EO than IO embryos, whereas during the later stages corticosterone increased dramatically in the shelled embryos, and remained relatively constant in the EO embryos. 4. EO embryos do not exhibit a pattern of adrenal hormonal secretion that would indicated a stressful condition. 5. The absence of a normal increase in corticosterone in shell-less embryos may contribute to the abnormal embryological development in the later stages of incubation.

Animals↗

Recruitment of peripheral mononuclear cells by mammalian collagenase digests of type I collagen.

Type I collagen is highly susceptible to proteolytic cleavage by neutral mammalian collagenase. Following an initial site specific cleavage of the substrate, two characteristic products are generated, TCA and TCB. These two products then spontaneously denature and are degraded into multiple smaller molecular weight peptides. We prepared TCA and TCB from native type I collagen by the action of rat uterine fibroblast neutral collagenase. In addition we prepared denatured type I alpha chains and exposed them to the action of collagenase under controlled conditions in order to generate small molecular weight peptides. We then examined intact type I collagen, TCA and TCB and type I gelatin peptides for chemotactic activity in a Boyden chamber assay using both human peripheral monocytes and polymorphonuclear leucocytes as target cells. Intact type I collagen, while chemotactic for neutrophils, failed to elicit any chemotactic response in mononuclear cells. In addition, the results demonstrate an absence of any detectable chemotactic activity for either TCA or TCB when human peripheral monocytes were used as the target cells. However, type I collagen peptides demonstrated chemotactic activity for peripheral monocytes. Maximum cell migration was found with digests which had been exposed to neutral mammalian collagenase for three to four hours. No chemotactic activity was found using the same peptides, when neutrophils were used as the target cells. The data strongly suggest that chemotactic activity for mononuclear cells, normally suppressed in intact type I collagen, is revealed and/or activated by neutral collagenase digestion. Conversely, chemotactic activity for neutrophils is lost when intact type I collagen is digested into smaller molecular weight fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Movement↗

Oncogenic transformation following sequential irradiations with monoenergetic neutrons and X rays.

Mouse C3H 10T1/2 cells were exposed sequentially to low doses (0.1 and 0.3 Gy) of monoenergetic neutrons (0.35, 0.45, 5.9, and 13.7 MeV) and 250-kVp X rays (1 and 3 Gy). The incidences of oncogenic transformation in the cells exposed to neutrons followed by X rays indicated that the effects of the individual radiations were simply additive. This supports the contention that risks associated with the two different radiation modalities may be considered to be additive.

Animals↗

Eysenck's incubation of fear hypothesis: an experimental test.

The present experiment was designed to test Eysenck's hypothesis that repeated exposure to an unreinforced CS of brief duration following acquisition of a classical aversive CR may lead to a progressive increase in the strength of that CR, provided that the UCS is intense and the CR has drive-like properties. Using a between-groups design, normal human subjects were given identical classical acquisition trials, followed by extinction trials where CS duration was either 2, 8 or 16 sec. The UCS was of fixed high intensity. Dependent measures were tonic and phasic heart rate and skin conductance. No evidence of incubation was found as a function of CS duration. Nor was there any indication that CS duration differentially affected resistance to extinction. A small number of subjects showed evidence of incubation with heart rate measures during extinction. However, there was no indication that this enhancement was governed by the parameters suggested by Eysenck. UCR amplitude, which showed a positive correspondence with CS-bound activity throughout the trials, did not reliably predict incubation. Problems concerning both the definition and the demonstration of incubation are discussed.

Adolescent↗

Inhibition of endopeptidase EC 24.11 in humans. Renal and endocrine effects.

The effects of an orally active inhibitor (UK 79300) of the neutral metalloendopeptidase EC 3.4.24.11 were investigated in six healthy male volunteers maintained on a constant diet (150 mmol sodium/day and 80 mmol potassium/day). Subjects were studied in a random order, single-blind study on two occasions, each 48 hours in length, when they were given UK 79300 (25 or 50 mg p.o.) or placebo at 12-hour intervals (each agent for 24 hours). The endopeptidase inhibitor enhanced plasma concentrations of atrial natriuretic factor in association with suppression of both plasma renin activity and aldosterone concentrations. Twenty-four-hour urinary excretion of sodium was doubled by UK 79300, and the urinary excretion rates of phosphorus, atrial natriuretic factor immunoreactivity, and cyclic guanosine monophosphate were also significantly enhanced, whereas urinary aldosterone excretion was halved. The profile of biological effects closely paralleled those previously reported with low dose infusions of atrial natriuretic factor in humans and animals. Therapeutic trials of such inhibitors are now indicated for hypertension or heart failure together with further studies to clarify the underlying mechanisms of action.

Adult↗

Brain natriuretic peptide administered to man: actions and metabolism.

To investigate the effects and metabolism of brain natriuretic peptide (BNP) in man, eight normal subjects received 3-h infusions of synthetic porcine BNP (2 pmol/kg.min) in a placebo-controlled study. The MCR and plasma half-life of BNP were 2.69 L/min and 3.1 min, respectively. BNP clearly suppressed PRA to less than 50% of placebo values (P less than 0.001). Plasma aldosterone concentrations were also significantly reduced by 30% (P less than 0.05). Urinary sodium excretion tended to rise (P = 0.054), and urinary cGMP excretion was clearly enhanced (P less than 0.01). Systemic and renal hemodynamics, hematocrit, plasma protein concentrations, plasma ACTH, arginine vasopressin, PRL, and catecholamines were unchanged. Porcine BNP has a similar range of effects and is similarly metabolized in man as human ANP. Further elucidation of the possible role of BNP as a circulating hormone in man awaits measurement of tissue and plasma concentrations of human BNP in health and disease and provision of fuller dose-response data for human as well as porcine BNP.

Adult↗

Burnout among primary care physicians and mental health professionals in a managed health care setting.

This study assessed burnout within a large Health Maintenance Organization. Primary care physicians and one psychiatric clinic staff were studied. The Maslach Burnout Inventory was used to develop frequency data in the areas of emotional exhaustion, depersonalization, and personal achievement. Among the primary care physicians, moderate emotional exhaustion, and depersonalization were found. Personal achievement was high. Among the psychiatric staff, high emotional exhaustion and depersonalization were found. Again, personal achievement was high. The entire professional group, with the one exception, was significantly higher in emotional exhaustion, depersonalization, and personal achievement than Maslach's normative sample. Psychiatrists and social workers had significantly higher scores on depersonalization than the primary care physicians or psychologists. High burnout in a Health Maintenance Organization setting suggests that managed health care providers may be more prone to burnout than fee-for-service practitioners. Several suggestions were made for such organizations to help alleviate burnout in their staffs.

Adult↗

Skin to skin contact for very low birthweight infants and their mothers.

Separation between mothers and very low birthweight infants is often prolonged with subsequent psychological distress, behaviour problems, and lactation failure. Babies as small as 700 g, who no longer require oxygen, can be safely and enjoyably held naked, except for a nappy, between the mother's breasts for up to four hours a day. We have carried out a randomised trial among babies less than 1500 g. Seventy one infants were randomised. In 35, the mother was helped to hold her baby in skin to skin contact and encouraged to do so whenever she visited the baby. In 36, the mother was encouraged to handle her baby but without skin to skin contact. Mothers using skin to skin contact lactated for four weeks longer on average than the control group. At 6 months of age the infants who had skin to skin contact cried significantly less than the control group. Skin to skin contact can safely and enjoyably be offered to very low birthweight infants especially in developing countries where the mother's lactation is vital.

Child Behavior↗

alpha 2HS glycoprotein is chemotactic for mononuclear phagocytes.

alpha 2HS glycoprotein is a normal constituent of plasma. It has a high affinity for hydroxyapatite and is concentrated in bone 100-fold greater than albumin, however its biological function in bone is not known. We have purified alpha 2HS from human plasma and examined it for evidence of chemotactic activity against human peripheral mononuclear cells, polymorphonuclear leucocytes and lymphocytes in Boyden chamber assays. We observed that the protein was chemotactic for mononuclear cells and that maximal cell migration occurred when its concentration in the lower compartment of Boyden chambers was 10(-10) M. Chemotaxis did not occur in the absence of a concentration gradient. In addition, cell migration was blocked when the cells were preincubated with 10(-10) M alpha 2HS or when the protein was preincubated with rabbit anti-human alpha 2HS glycoprotein IgG. Neither polymorphonuclear leucocytes, which are responsive to a wide range of chemoattractants, or peripheral lymphocytes exhibited directed migration to alpha 2HS in Boyden chamber assays. The glycoprotein appears therefore to act as a chemotaxin directed to monocyte recruitment, and we speculate that the protein may have an important role in monocyte recruitment to bone and possibly their subsequent fusion and differentiation into functional osteoclasts.

Blood Proteins↗