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Biomedical subjects

K Clark

Publications and source records attributed to K Clark.

At least 145 records · Page 8Linked to original sources
PubMed1993

Low dose fructose ingestion during gestation and lactation affects carbohydrate metabolism in rat dams and their offspring.

This study examined whether drinking fructose or glucose water with a balanced diet affects pregnant and lactating rats and their offspring. The animals were divided into three groups and drank tap water, 100 g/L fructose water or 100 g/L glucose water. The fructose-fed dams ate significantly more food but drank less water than the glucose-fed group. On d 19 of pregnancy, the fructose-fed dams had significantly heavier livers and significantly higher plasma glucose and insulin concentrations than dams consuming tap water. Five days after litters were weaned, dams fed fructose had the heaviest body weights, significantly higher plasma glucose concentration compared with the group receiving tap water and significantly higher plasma triglyceride concentration compared with the glucose-fed group. Weanlings of the fructose-fed dams had significantly lower plasma glucose concentration but a significantly higher plasma insulin concentration than the weanlings of the group receiving tap water. These findings suggest that intake of fructose during gestation can cause hyperglycemia and hyperinsulinemia in dams and, at weaning, greater weight gain in dams and hyperinsulinemia in offspring. These abnormalities in dams and weanlings could be the result of insulin resistance.

Adipose Tissue↗
PubMed1993

Renal allograft rejection: examination of adhesion blockade by antilymphocyte antibody drugs.

An assay was developed to investigate the binding of lymphocytes to cultured human renal epithelial cells. This binding was increased following lymphocyte activation by culture either with a polyclonal mitogen or with allogeneic stimulator cells. It was shown that such activation increased lymphocyte expression of the adhesion molecules CD2, LFA-1, and VLA-4. The ligand for each of these molecules was demonstrated on the surface of cultured renal epithelial cells. Polyclonal antilymphocyte antibody (ALA) preparations are used frequently to reverse intractable episodes of acute renal allograft rejection. It was demonstrated that such agents reduce the binding of activated lymphocytes to renal epithelial cells and subsequent cell lysis with a similar dose-response curve. Application of this assay may allow improved evaluation and titration of therapeutic antibody preparations. A range of monoclonal antibodies specific for components of the three adhesion molecule systems investigated in this work were added to lymphoid cell binding assays. It was found that combinations of these antibodies designed to interfere simultaneously with each of these adhesion interactions inhibited binding less well than the ALA preparation. It is likely that the superior inhibition of binding produced by ALA is due to the polyclonality of the antibodies which can block multiple epitopes on a wide range of potential adhesion molecules.

Antibodies, Monoclonal↗
PubMed1992

A national model of faculty development in addiction medicine.

Increasing the number of faculty with expertise in addiction medicine is one of the challenges facing the medical community in the 1990s. To meet this challenge, the Society of Teachers of Family Medicine created a faculty development course to increase the expertise of family practice faculty involved in teaching residents. The authors describe the development, implementation, and consequences of the five-day intensive course that was taught to 165 participants at ten sites in 1990. The participants' self-reporting before and three months after the course showed significant increases in the numbers of participants who taught addiction medicine in eight of 11 clinical situations. The authors conclude that the course represents a model of faculty development in addiction medicine that is applicable to other specialties and health professions.

Evaluation Studies as Topic↗
PubMed1992

Renal allograft rejection: induction and function of adhesion molecules on cultured epithelial cells.

The interaction of graft-infiltrating immune cells with donor parenchymal cells is an important early event in allograft rejection. This binding is stabilized by interaction of antigen-independent 'adhesion' molecules expressed on the two cell types. As the level of expression of these molecules can be altered during inflammation, a series of experiments was performed to examine the effects of the inflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on adhesion molecules expressed by cultured human renal tubular epithelial cells. These cells constitutively expressed ICAM-1 and LFA-3. Incubation with IFN-gamma increased expression of ICAM-1 but had no significant effect on expression of LFA-3 (P greater than 0.05). Incubation with TNF-alpha increased expression of both ICAM-1 and LFA-3; IFN-gamma synergized with TNF-alpha to further augment expression of these molecules. Peripheral blood lymphocytes (PBL) showed an enhanced binding to allogeneic renal epithelial cell monolayers which had been pretreated with IFN-gamma or TNF-alpha. MoAbs specific for ICAM-1 or its ligand LFA-1 inhibited adhesion of PBL to either IFN-gamma- or TNF-alpha-pretreated renal cells. By contrast, antibodies specific for LFA-3 or its ligand CD2 only significantly blocked PBL adhesion to renal cells which had been pretreated with TNF-alpha. Combination of antibodies specific for multiple components of the adhesion systems produced greater inhibition of adhesion than was produced by any single MoAb. These results suggest that the inflammatory cytokines IFN-gamma and TNF-alpha up-regulate expression of functional ICAM-1 and LFA-3 molecules which can augment the binding of potentially graft-damaging lymphoid cells to renal tubular epithelial cells.

Antigens, CD↗
PubMed1992

Differences in lingual vibrotactile threshold shifts during magnitude-estimation scaling between normal-speaking children and children with articulation problems.

The purpose of this study was to investigate differences in function of the tactile sensory system between groups of normal-speaking children and children with articulation problems. This task was accomplished by studying possible tactile threshold shifts occurring during magnitude-estimation scaling of vibratory stimuli presented to the dorsal surface of the tongue. 10 normal-speaking children (M age = 7.8 yr.) and 9 children with articulation problems (M age = 7.5 yr.) participated. The normal-speaking children and articulatory defective children performed differently on the magnitude-estimation scaling task in which threshold was allowed to return to baseline after each stimulus presentation. These two groups of children also showed dissimilar threshold shifts for the suprathreshold intensities employed in the magnitude-estimation scaling.

Articulation Disorders↗
PubMed1991

The accuracy of self-reported hearing loss in women aged 60-85 years.

The accuracy of self-report in identifying individuals with hearing impairment was evaluated in 1988 in 267 women from rural Iowa. Using pure-tone threshold audiometry as the standard, self-reported hearing loss was a sensitive and specific indicator of measured losses of 40 decibel hearing level for pure-tone averages of either 1,000 and 2,000 Hz or 1,000, 2,000, 3,000 and 4,000 Hz (sensitivities, 90% and 84%; specificities, 71% and 75%, respectively). Predictive values positive were low (28% and 42%) in this population where hearing loss prevalence was 11-18%, but would be increased to acceptable levels in populations with a prevalence of approximately 30%.

Aged↗
PubMed1991

Unexplained rabies in three immigrants in the United States. A virologic investigation.

BACKGROUND: Extensive investigation of three patients who died of rabies in the United States failed to reveal any source of exposure to the disease. The three patients had immigrated to the United States from areas in Laos, the Philippines, and Mexico where rabies is endemic. METHODS: We studied rabies viruses isolated from the three patients, other patients with a known source of exposure, and animals in the United States, Thailand (as a proxy for Laos), the Philippines, and Mexico. The viruses were characterized by indirect immunofluorescence and neutralization tests according to their reactions to panels of monoclonal antibodies. Transcribed complementary DNA from these isolates was amplified by the polymerase chain reaction; the DNA product was then analyzed by differential digestion with restriction enzymes. RESULTS: The viral isolate from each of the three patients was a rabies variant with distinctive antigenic or genetic characteristics. For each of the three isolates, identical variants were found in specimens from rabid animals obtained from or near the country in which the patient lived before immigrating to the United States. None of these variants were found among the isolates collected from rabid animals in the United States. CONCLUSIONS: Rabies infection in these three patients did not originate in the United States but resulted from exposures in Laos, the Philippines, and Mexico. Since the three patients had lived in the United States for 4 years, 6 years, and 11 months, our findings suggest that the onset of the clinical manifestations of rabies occurred after long incubation periods.

Adolescent↗
PubMed1991

Factors influencing the ocular pulse--axial length.

The amplitude of the intraocular pressure pulse and pulsatile ocular blood flow (POBF) were correlated with the axial length and refraction of 68 eyes of healthy subjects. Measurements were obtained with subjects in the sitting position using an ophthalmic A-scan and a pneumotonometer linked to a Langham ocular blood-flow system. The amplitude of the ocular pulse and the magnitude of POBF were found to decrease with increasing axial length (r = -0.61, P less than 0.001 and r = -0.74, P less than 0.001, respectively). A similar close relationship was found between the ocular pulse amplitude and POBF and the refractive state of the eye (r = 0.63, P less than 0.001 and r = 0.7, P less than 0.001, respectively). The reasons for the association are discussed and the importance of the observations in the construction of studies in which ocular pulse amplitude or POBF are to be measured in different groups of subjects is emphasised.

Adolescent↗
PubMed1991

Prospective study of radial bone mineral density in a geographically defined population of postmenopausal Caucasian women.

The radial bone mineral density (BMD) mass of 324 Caucasian women, aged 55-80 years, from geographically defined areas was evaluated in 1983 using single photon absorptiometry; 271 of these women (86%) were reexamined 5 years later in 1988. More than 65% of women lost radial BMD in excess of 1%/year in the 5-year follow-up. Thirty percent of women lost at least 2%/year. Baseline radial BMD measures taken in 1983 were highly predictive of the 1988 radial BMD values, explaining approximately 82% of the variability. The rate of bone change, expressed as percent change or 5-year difference (g/cm2), was not associated with baseline radial BMD value. Rate of change was not strongly associated with chronologic age or years since menopause, even when data were restricted to those women who reported no previous use of perimenopausal estrogen or thiazide medication. We conclude that BMD loss in a general population may be more substantial than previously believed.

Absorptiometry, Photon↗
PubMed1991

A prospective study of physical trauma and multiple sclerosis.

During an eight year period 170 multiple sclerosis (MS) patients and 134 controls without physical impairment were followed closely to record all episodes of physical trauma and to measure their effect on exacerbation rate and progression of MS. There was a total of 1407 instances of trauma, which were sorted into various categories. Overall there was no significant correlation between all-traumas and disease activity. There was, however, a statistically significant negative correlation between traumatic episodes and exacerbations in 95 patients who had exacerbations during the programme, due primarily to less activity of the disease during a three month period following surgical procedures and fractures. Electrical injury had a significant positive association with exacerbation using a three month at-risk period, but there were no other significant positive correlations in any other category of trauma, including minor head injuries; there were no cases of head injury with prolonged unconsciousness. There was no linkage between the frequency of trauma and progression of disability. MS patients had two to three times more trauma than controls.

Adult↗
PubMed1991

Renal allograft rejection: investigation of alloantigen presentation by cultured human renal epithelial cells.

Defined lines of primary human renal epithelial cells were established and their expression of class II major histocompatibility (MHC) antigens was up-regulated by culture with interferon-gamma (IFN-gamma). The ability of these cells to stimulate the proliferation of allogeneic peripheral blood mononuclear cells (PBMC) was compared with that of endothelial cells and splenic mononuclear cells. It was found that both endothelial and splenic cells stimulated lympho-proliferation but that cultured renal epithelial cells were non-stimulatory. The failure of proliferation by allogeneic lymphocytes in culture with epithelial cells was not overcome by treatment with interleukin-1 (IL-1) or indomethacin. However, addition of IL-2 to mixed cultures of allogeneic PBMC and renal epithelial cells stimulated lympho-proliferation and allowed the generation of lymphoid cell lines which mediated non-specific lysis of renal epithelial cell lines. Stimulation of PBMC by mixed lymphocyte culture yielded an allospecific T-cell line which was added either to renal epithelial cells from the same donor as the stimulator cells used in the priming reaction or from a third-party donor; lympho-proliferation was observed in the specific secondary reaction but not in the non-specific reaction. These findings indicate that class II MHC antigen-expressing epithelial cells within a renal allograft may not initially stimulate the proliferation of resting allospecific recipient lymphocytes. However, within a rejecting graft it is likely that high local concentrations of IL-2 are present and that many of the infiltrating allospecific lymphocytes will be primed by previous contact with donor antigen-presenting cells, such as vascular endothelial cells or dendritic cells. Therefore, expression of class II MHC antigens by epithelial cells within the microenvironment of a renal allograft may render such cells immunogenic and able to play a direct role in the lymphocyte-mediated intragraft rejection process.

Antigen-Presenting Cells↗
PubMed1990

Crico-tracheal disruption and common carotid artery occlusion: a case of blunt trauma.

A case of blunt trauma to the neck is presented. While driving an all terrain vehicle (ATV), a 20-yr-old male was struck across the anterior neck by a cord suspended between two poles. Initial findings were suggestive of an isolated laryngeal injury; 48 hours later, however, a dense left hemiplegia became manifest. A CT scan demonstrated a large right frontoparietal cerebral infarct, and an angiogram confirmed occlusion of the right common carotid artery. Intractable cerebral oedema developed, and the patient died five days after the initial insult. Such injuries should alert the clinician to the possibility of major vascular injury, and if suspected, angiography is warranted.

Adult↗
PubMed1990

The effects of oral hydralazine on blood pressure, cardiac output and peripheral resistance with respect to dose, age and acetylator status.

Cardiovascular responses are reported in 21 patients with carcinoma of the bronchus taking part in a study of tumour perfusion. There were eight slow and 12 fast acetylators; acetylator status was not determined in one patient with a history of sulphonamide allergy. Hydralazine dose ranged from 25 to 150 mg orally (equivalent to 0.37 to 2.86 mg/kg). Mean arterial blood pressure fell from 98 mmHg before hydralazine to 90 mmHg 60 min after hydralazine (p = 0.002) and mean cardiac output rose from 5.53 l/min to 7.75 l/min (p = 0.00005). Calculated total peripheral resistance fell by 30% (p = 0.0002). Falls in peripheral resistance per milligram hydralazine administered were greater in patients over 70 years of age. Acetylator status was a poor predictor of response. Side-effects were reported by eight patients and were related to the magnitude of fall in peripheral resistance (p = 0.0005) but not to falls in blood pressure (p = 0.12).

Acetylation↗
PubMed1990

Mechlorethamine, vincristine, and procarbazine chemotherapy for recurrent high-grade glioma in adults: a phase II study.

We undertook a phase II study of combination chemotherapy with mechlorethamine (nitrogen mustard) 6 mg/m2 intravenously day 1 and day 8, vincristine 2 mg intravenously day 1 and day 8, and procarbazine 100 mg/m2 orally days 1 through 14 (MOP) in adults with recurrent high-grade glioma. There were 31 patients entered and 27 patients assessable for response. The median age was 49 years old. All patients had prior maximal radiotherapy, and eight had previous chemotherapy. Responses were determined based on clinical and computed tomographic (CT) scan/magnetic resonance imaging (MRI) criteria. The response rate (partial response [PR] plus objective qualitative response [OQR] plus complete response [CR]) was 52% with one CR. The response rate was higher in patients with anaplastic astrocytoma as compared with glioblastoma multiforme (P less than .05). The median duration of response was 42 weeks. Median survival for all assessable patients was 30 weeks, and for responders, it was 60 weeks. Response was correlated with ability to decrease dexamethasone doses and improved performance status. Toxicity was mainly hematologic with leukopenia being common. There was one treatment-related death from listeria meningitis, and two patients developed Pneumocystis carinii pneumonia. There were three episodes of neutropenic fever. We conclude that MOP is active and merits further investigation in adult high-grade glioma.

Adult↗
PubMed1990

Optical spectroscopy (INVOS) is unreliable in detecting breast cancer.

Recently a new nonionizing, nonimaging technique for evaluating risk of breast cancer, in vivo optical spectroscopy (INVOS), became available. The procedure evaluates the biochemical composition of the breast with spectrophotometry to provide a risk number related to the development of breast cancer. INVOS was evaluated in a prospective study of 180 women who were referred to our institution for needle localization and excisional biopsy of 181 breast lesions. All women had mammography and INVOS before surgical biopsy. The INVOS risk numbers and mammographic findings were compared with the pathologic diagnoses. Of 39 breast cancers, 19 (49%) had high-risk INVOS numbers, as did 52% of women with benign disease. INVOS had a sensitivity of 95%, specificity of 4%, and a positive predictive value of 21% for the detection of breast cancer. Mammography predicted malignancy with a sensitivity of 97%, specificity of 48%, and a positive predictive value of 34%. Receiver-operating-characteristic (ROC) curve analysis also was performed. The ROC area for mammography was 0.85 compared with 0.43 for INVOS, indicating a significantly greater (p less than .0000001) ability for mammography to detect breast cancer. We conclude that because INVOS cannot accurately predict the presence of breast cancer, it is unlikely that INVOS can be used to predict which patients are at risk for the development of breast cancer.

Adenofibroma↗