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Biomedical subjects

R Spark

Publications and source records attributed to R Spark.

At least 19 recordsLinked to original sources
PubMed2004

Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part B: Reduced serum androgen levels in healthy premenopausal women with complaints of sexual dysfunction.

Androgen insufficiency has been associated with decreased libido and arousal in postmenopausal women, but rarely has been evaluated in healthy premenopausal women. In all, 32 healthy premenopausal women were enrolled in this study, 18 with one or more complaints of sexual dysfunction and 14 without. Assays of ovarian and adrenal androgens were measured before and after ACTH stimulation. The women with complaints of sexual dysfunction had significantly lower adrenal androgens than did the control women. There were no differences in the basal ovarian androgens or cortisol levels. After ACTH, both groups stimulated cortisol as well as adrenal and ovarian androgens. In conclusion, premenopausal women with complaints of sexual dysfunction had lower adrenal androgen precursors and testosterone than age-matched control women without such complaints. Further study is required to determine how lower adrenal androgens contribute to female sexual dysfunction.

Adrenal Glands↗
PubMed2004

Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part A. Serum androgen levels in women aged 20-49 years with no complaints of sexual dysfunction.

Androgen insufficiency is a recognized cause of sexual dysfunction in men and women. Age-related decrements in adrenal and gonadal androgen levels also occur naturally in both sexes. At present, it is unclear if a woman's low serum androgen level is a reflection of the expected normal age-related decline or indicative of an underlying androgen-deficient state. We studied premenopausal women with no complaints of sexual dysfunction to help define a normal female androgen profile. In all, 60 healthy, normally menstruating women, ages 20-49 y, were studied. The Abbreviated Sexual Function Questionnaire was administered along with a detailed interview. Radioimmunoassay measurements of morning serum testosterone (T), free testosterone (fT), dehydroepiandrosterone-sulfate (DHEAS), sex hormone-binding globulin (SHBG), and free androgen index (FAI) were measured during days 8-15 of the menstrual cycle. In women 20-49 y old without complaints of sexual dysfunction, serum androgen levels exhibit a progressive stepwise decline. Comparing values obtained in women age 20-29 y to those obtained in women 40-49 y, specific hormone decrements were DHEAS 195.6-140.4 microg/dl, serum T 51.5-33.7 ng/dl, fT 1.51-1.03 pg/ml. SHBG did not change significantly in women in this age group. The FAI reflected the age-related decrease in female androgen levels. The framework for the development of a female androgen profile in women with no complaints of sexual dysfunction has been established, and an age-related decrease in testosterone and its adrenal precursor, DHEAS, has been demonstrated. The FAI mirrors these decreases and its usefulness in clinical practice is confirmed. A precipitous decline in all androgens occurs after the decade of the 20s, yet SHBG does not show a significant change throughout the premenopausal years.

Adult↗
PubMed2003

Opposing effects of low and high-dose clozapine on survival of transgenic amyotrophic lateral sclerosis mice.

Clozapine is a potent atypical neuroleptic or antipsychotic agent used to relieve symptoms of early-diagnosed schizophrenia. Aside from well-described dopamine and serotonin receptor blockade effects, clozapine may also be neuroprotective through its modulation of the p75 neurotrophin receptor (p75(NTR)) and superoxide dismutase 1 (SOD1) expression. The death-signalling activities of both p75(NTR) and mutant SOD1 are implicated in motor neuron degeneration in humans and transgenic mice with amyotrophic lateral sclerosis (ALS). We therefore investigated the effects of clozapine in cell culture and mouse models of ALS. Clozapine dose-dependently inhibited full-length and cleaved p75(NTR) but not SOD1 protein expression in the motor neuron-like (NSC-34) cell line. Furthermore, low concentrations of clozapine protected NSC-34 cells from paraquat-mediated superoxide toxicity, nerve growth factor (NGF)-induced death signalling, and serum deprivation, whereas high concentrations potentiated death. Systemic thrice-weekly administration of low and high-dose clozapine to mutant superoxide dismutase 1 (SOD1(G93A)) mice produced differential effects on disease onset and survival. Low-dose treatment was associated with delayed locomotor impairment and death, compared to high-dose clozapine, which accelerated paralysis and mortality (P < 0.05). Increased death was not attributable to toxicity, as clozapine-induced agranulocytosis was not detected from blood analysis. High-dose clozapine, however, produced extrapyramidal symptoms in mice manifest by hindlimb rigidity, despite reducing spinal cord p75(NTR) levels overall. These results suggest that although clozapine may exert p75(NTR)-mediated neuroprotective activity in vitro, its profound antagonistic effects on dopaminergic and serotonergic systems in vivo at high doses may exacerbate the phenotype of transgenic ALS mice.

Amyotrophic Lateral Sclerosis↗
PubMed1997

The effect of PTH antagonist BIM-44002 on serum calcium and PTH levels in hypercalcemic hyperparathyroid patients.

BIM-44002, a pure competitive antagonist of parathyroid hormone (PTH), has a high affinity for the PTH/PTHrP receptor in vitro, and can completely inhibit the actions of a PTH agonist in rats in vivo. Toxicology studies in rats and dogs showed BIM-44002 to be devoid of any adverse effects. Therefore we undertook an investigation to evaluate the potential utility of BIM-44002 in lowering elevated serum calcium in three patients with primary hyperparathyroidism. BIM-44002 was administered by continuous intravenous infusion at dosages of 100 microg/hour (370 nmol/hour) for 12 hours, followed by 200 microg/hour for 12 hours, followed by 400 microg/hour for 12 hours. Vital signs and serum ionized and total calcium were monitored hourly and for 3 hours after cessation of the infusion. Blood for PTH determinations was obtained at the same time points. Serum calcium and PTH did not change during and after the infusion of the antagonist. No subject experienced any adverse reactions to the infusion of the antagonist. We conclude that although the PTH antagonist BIM-44002 was effective both in vitro and in vivo in animals, and it was safe in humans, it was not able to lower serum calcium in patients with hyperparathyroidism. Possible reasons for lack of clinical efficacy are discussed.

Adult↗
PubMed1997

Loxosceles arizonica bite associated with shock.

Envenomation by the brown recluse spider (Loxosceles reclusa) is associated with shock, significant hemolysis, renal insufficiency, and disseminated intravascular coagulation (DIC). Shock has never been associated with envenomation by L arizonica, a related species indigenous to Arizona, southern California, and northwestern Mexico. We report the case of a 13-year-old girl, bitten by a specimen of L arizonica (the spider was identified by an entomologist), in whom shock and a typical cutaneous lesion developed. She did not experience renal insufficiency or disseminated intravascular coagulation. Infectious causes of shock were excluded. She recovered completely with supportive care.

Adolescent↗
PubMed1997

Intractable hypercalcaemia due to parathyroid hormone-related peptide secretion by a carcinoid tumour.

Hypercalcaemia, a common complication of malignancy, may result from either the lytic effect of multiple osseous metastases or the effect of tumour-derived humoral factors. Excessive secretion of parathyroid hormone-related peptide (PTHrP), a major cause of humoral hypercalcaemia of malignancy, has been incriminated as the cause of hypercalcaemia in patients with lung, breast, renal, head and neck and, occasionally, haematological malignancies. Carcinoid tumours, while frequently the source of ectopic hormone secretion, are infrequently associated with hypercalcaemia. We report the case of a 59-year-old woman with fulminant hypercalcaemia due to excessive PTHrP secretion from a hepatic carcinoid and we present the change in her serum PTHrP concentrations during infusion of a somatostatin analogue.

Antineoplastic Agents, Hormonal↗
PubMed1997

Towards guidelines for survey research in remote Aboriginal communities.

Based on our experience in developing and evaluating community-based health promotion programs in Aboriginal and Torres Strait Islander communities, we offer guidelines to assist nonindigenous health and public policy professionals whose information gathering in these communities includes the use of unstructured interviewing or survey questionnaires. The guidelines primarily apply to research among mainland remote Aboriginal communities, but are placed in a cultural context such that those dealing with Torres Strait Islanders and rural or urban community Aborigines also may benefit from the guidelines. The major aims of these guidelines are to facilitate communication between interviewers and indigenous interviewees and to ensure that interviewing is done with maximum sensitivity to cultural differences and with minimum discomfort to the respondents.

Australia↗
PubMed1991

Age specific patterns of change in the dynamics of Wuchereria bancrofti infection in Papua New Guinea.

Results of a longitudinal study of the age-specific dynamics of Wuchereria bancrofti infection in a community of East Sepik Province, Papua New Guinea (PNG) are described. Microfilarial (mf) density and serum levels of W. bancrofti phosphorylcholine-containing antigen (PC-Ag) in individuals were used as indirect measures of adult worm burden. These parasitological data were collected from 126 subjects greater than 4 years of age at two time points, 12 months apart, prior to the administration of the antifilarial drug diethylcambamazine (DEC). No significant changes in levels of mf density were observed for the study population between these two time points. However, significant changes in the levels of circulating PC-Ag were noted in subjects less than or equal to 20 years of age, but not in subjects greater than 20 years of age, between these two time points. The apparent shorter half life of circulating PC-Ag compared to that of mf makes antigenemia a more sensitive measure of the dynamics of adult worm populations. These data are discussed in terms of a basic mathematical model describing the dynamics of adult worm populations in relation to their life expectancy and attrition of larvae during establishment. Consideration of these data in the context of this simple immigration/death model suggests that the differences observed in patterns of change in intensity of infection between subjects less than or equal to 20 years old and those greater than 20 years old may be consistent with the acquisition of resistance to superinfection with increasing age.

Adolescent↗
PubMed1991

Serological evaluation of the macrofilaricidal effects of diethylcarbamazine treatment in bancroftian filariasis.

An Mr 200,000 phosphorylcholine-containing antigen (PC-Ag) of predominantly adult worm origin was found in the sera of humans infected with Wuchereria bancrofti. This paper describes results of a longitudinal study of changes in levels of PC-Ag in response to diethylcarbamazine (DEC) therapy as measured by two-site immunoradiometric assay (IRMA) and Western blotting. One hundred thirty-two residents of a bancroftian filariasis-endemic area of Papua New Guinea (PNG) were treated with a 72 mg/kg dose of DEC. A macrofilaricidal effect was seen with this dose of DEC as 34% of the treated subjects had localized side effects and long-term decreases in microfilariae (mf) counts were observed 12 months after treatment. The PC-Ag levels were reduced to 72%, 52%, and 51% of pretreatment values at 21 days and at six and 12 months after treatment. These decreases, observed by IRMA, were specifically associated with loss of the Mr 200,000 PC-Ag detected by immunoadsorption and Western blotting. From drug treatment data, the maximum half-life of PC-Ag in circulation was calculated to be 50 days, assuming a first-order decay process. This maximum half-life indicates that persistent antigenemia observed in the majority of treated subjects could only result from the survival of adult worms. In the absence of methods to directly demonstrate W. bancrofti adult worms, detection of serum PC-Ag levels provides a sensitive indirect measure of the dynamics of adult worm populations. This serological measurement may be useful in optimizing the macrofilaricidal and therapeutic effects of DEC and in assessing the macrofilaricidal action of new antifilarial drugs and immunological interventions.

Adolescent↗
PubMed1985

Syndrome of camptodactyly, ankyloses, facial anomalies, and pulmonary hypoplasia (Pena-Shokeir syndrome): obstetric and ultrasound aspects.

Two siblings with Pena-Shokeir syndrome are described. This syndrome consists of polyhydramnios, intrauterine growth retardation, short umbilical cord, perinatal death, facial abnormalities, limb abnormalities including arthrogryposis, and lethal pulmonary hypoplasia. The mode of inheritance is most likely autosomal recessive. Prenatal diagnosis was made in the second pregnancy with ultrasound performed at 26 weeks' gestation. The roles of fetal akinesia and fetal apnea in the production of the various manifestations of the syndrome are detailed, and the possibility of early prenatal diagnosis is considered.

Abnormalities, Multiple↗
PubMed1985

Non-Hodgkin's lymphoma limited to the adrenal gland with adrenal insufficiency.

A 81-year-old man presented with bilateral adrenal masses found pathologically to be a large cell, non-follicular center, non-Hodgkin's lymphoma. His clinical course was remarkable for the lack of macroscopic extra-adrenal tumor and for adrenal insufficiency in response to stress and cosyntropin stimulation. This is believed to be the first reported case of a non-Hodgkin's lymphoma limited to the adrenal glands with associated adrenal insufficiency.

Adrenal Gland Neoplasms↗
PubMed1985

A monoclonal antibody-based immunoradiometric assay for detection of circulating antigen in Bancroftian filariasis.

A monoclonal antibody designated Gib 13 has been used in an immunoradiometric assay (IRMA) to detect circulating antigen in the sera of Wuchereria bancrofti-infected subjects from an endemic area of Papua New Guinea. A clear association between the presence of patent infection and the Gib 13 target epitope in serum was established because 93% of microfilaremic individuals were antigen-positive. Moreover, there was a significant correlation between levels of serum antigen and blood microfilarial counts. Detection of circulating antigen in amicrofilaremic subjects with acute symptoms of lymphatic filariasis, and 53% of asymptomatic amicrofilaremic subjects, but not in nonendemic controls, suggests that the Gib 13 IRMA will also be of value in the diagnosis of occult filariasis. However, as in all IRMA based on detection of potentially immunogenic molecules in man, antibodies can be expected to be the major contributor to reduced sensitivity of the assay.

Adolescent↗
PubMed1984

An affinity technique for the isolation of Clostridium perfringens type C from man and pigs in Papua New Guinea.

Necrotising enteritis caused by Clostridium perfringens type C (CwC) is an important cause of morbidity and death in highland regions of Papua New Guinea (PNG) and the organism is readily isolated from clinical cases. Although detected in fluorescent antibody stains of faecal cultures, CwC has previously only once been isolated from normal people or from pigs in PNG. The difficulty results from the greater numbers of the much more common Cl. perfringens type A (CwA) which is morphologically and culturally indistinguishable from CwC. Separation of CwC from the more numerous CwA has been achieved by utilising their antigenic dissimilarity. Silicate beads covered with specific antibody to CwC added to a mixed culture bound CwC cells while most of the unbound cells were washed away. When the beads were plated out type C organisms were recovered. In laboratory tests CwC was isolated from mixtures with CwA where the type A organisms predominated by one million to one. With this system type C organisms have been isolated from human and pig faeces from PNG.

Animals↗
PubMed1984

Parasitologic and clinical features of bancroftian filariasis in a community in East Sepik Province, Papua New Guinea.

Bancroftian filariasis has been reported in several areas of Papua New Guinea. The epidemiologic features and natural history of Wuchereria bancrofti infection in this geographic region, however, have not been well-defined. The objective of this study was to assess the parasitological and clinical features of bancroftian filariasis in a community in East Sepik Province, Papua New Guinea. In a village of 99 individuals, the overall prevalence of microfilaremia was 68%. The microfilarial carrier rate was high in those less than or equal to 10 years (62%), remained elevated in the 11-20, 21-30, and 31-40 age groups (42-55%), and peaked in subjects greater than or equal to 41 years old (90%). The geometric mean level of parasitemia in all subjects with patent infection was 3,198 microfilariae/ml blood. This value was 78 parasites/ml in the less than or equal to 10-year-old age group, increased to 1,753 in 21 to 30-year-olds and was markedly elevated in subjects greater than or equal to 41 years old (6, 792 microfilariae/ml). Acute symptoms of filariasis (lymphadenitis and lymphangitis) were initially noted in individuals between the ages of 11 and 20 years (30%). Obstructive disease, manifested as elephantiasis and hydroceles, was present in 64 and 79% of 31-40 and greater than or equal to 41-year-olds, respectively. These data suggest that intense transmission of W. bancrofti infection occurs at an early age in this area of East Sepik Province; patent infection remains high in older age groups. Irreversible lymphatic obstruction develops 20-30 years after initial infection and may be associated with either amicrofilaremia or microfilaremia.

Adolescent↗