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Biomedical subjects

K Holm

Publications and source records attributed to K Holm.

At least 19 recordsLinked to original sources

Intraepithelial gamma delta T-cell-receptor lymphocytes and genetic susceptibility to coeliac disease.

Although the proportion of gamma delta T-cell-receptor (TCR)-bearing intraepithelial lymphocytes is increased in the jejunum of patients with active coeliac disease, an abnormality thought to be specific among those with gluten-sensitive enteropathy, the factors influencing gamma delta TCR expression remain uncertain. We examined the relation between genetic factors associated with coeliac disease and intraepithelial gamma delta T lymphocyte distribution in both coeliac patients and their healthy first-degree relatives. 41% (45/109) of healthy relatives had an increased density of gamma delta T cells in their mucosa and 66% had an increased density of alpha beta T cells. By contrast with alpha beta T cells, the density of gamma delta cells was significantly associated with genetic markers for coeliac disease susceptibility (DR3, DQA, and DQB). We also found a dose effect of DQA and DQB genes on the number of intraepithelial gamma delta T cells. An increased density of gamma delta T cells in normal jejunal mucosa of a healthy individual with appropriate genetic determinants might be necessary for the development of the typical lesions of coeliac disease. Routine jejunal histological studies should include gamma delta T-cell counts, thus allowing early detection of coeliac disease latency.

Alleles

Serological markers and HLA genes among healthy first-degree relatives of patients with coeliac disease.

Coeliac disease may remain undiagnosed because of the non-specific nature of the presenting symptoms. Several antibody tests are claimed as markers for this condition but a direct comparison of the available tests has not been reported. The probands and healthy first-degree relatives of 42 families with coeliac disease were studied. Histological examination of biopsy specimens revealed jejunal mucosal villous atrophy compatible with coeliac disease in 13 of 122 relatives. Reticulin-antibody-positive relatives with or without jejunal mucosal atrophy were genetically similar to the probands of the families (DR3 gene frequencies 55.3%-60.0%). Gliadin-antibody-positive relatives with normal mucosa were genetically different from the probands (DR3 gene frequency 16.7% versus 55.3%). IgA reticulin and endomysium antibodies detected 92.3% of subjects with silent coeliac disease. The only case that was missed had selective IgA deficiency and was positive for IgG-class reticulin antibodies. By contrast, gliadin antibodies detected only half of the cases. Follow-up of the 7 reticulin-antibody-positive relatives with normal mucosa revealed 2 further cases of coeliac disease and 1 of dermatitis herpetiformis during the next three years. Our family study shows that healthy reticulin-antibody-positive first-degree relatives of coeliac disease patients, irrespective of the state of the jejunal mucosa, are genetically similar to known coeliac disease patients. Reticulin-antibody positivity is an indicator of both silent and latent coeliac disease.

Antibodies

Cloning and characterization of two mouse heat shock factors with distinct inducible and constitutive DNA-binding ability.

We have cloned two distinct mouse heat shock transcription factor genes, mHSF1 and mHSF2. The mHSF1 and mHSF2 open reading frames are similar in size, containing 503 and 517 amino acids, respectively. Although mHSF1 and mHSF2 are quite divergent overall (only 38% identity), they display extensive homology in the DNA-binding and oligomerization domains that are conserved in the heat shock factors of Saccharomyces cerevisiae, Kluyveromyces lactis, Drosophila, tomato, and human. The ability of these two mouse heat shock factors to bind to the heat shock element (HSE) is regulated by heat. mHSF1 is expressed in an in vitro translation system in an inactive form that is activated to DNA binding by incubation at temperatures greater than 41 degrees C, the same temperatures that activate heat shock factor DNA binding and the stress response in mouse cells in vivo. mHSF2, on the other hand, is expressed in a form that binds DNA constitutively but loses DNA binding by incubation at greater than 41 degrees C. Both mHSF1 and mHSF2 are encoded by single-copy genes, and neither is transcriptionally regulated by heat shock. However, there is a striking difference in the levels of mHSF1 mRNA in different tissues of the mouse.

Amino Acid Sequence

Alterations in splanchnic blood flow after low and high doses of ethanol.

The purpose of this investigation was to determine the effect of various acute doses of ethanol (1.0, 3.0, 4.0 g/kg) on the distribution of cardiac output (%CO) and blood flow to the splanchnic vascular bed in conscious male Wistar rats. Regional blood flow and cardiac output (CO) were measured by the reference microsphere technique. Mean arterial pressure and CO were significantly reduced 60 min after 3.0 g/kg and 4.0 g/kg of ethanol, while no changes occurred over time in total peripheral vascular resistance or heart rate. Acute ethanol administration produced an early non-sustained increase in portal vein blood flow, that was most pronounced after a low dose of ethanol, and was attenuated after the 3.0 g/kg and 4.0 g/kg doses of ethanol. The early increase in portal vein blood flow produced a corresponding increase in total liver blood flow. Additionally, we found increases in hepatic arterial blood flow after the higher doses. The combined increase in portal vein and hepatic arterial supply to the liver may serve to increase oxygen delivery, more than the singular increase in portal vein blood flow. This early increase in total liver blood flow after high doses of ethanol may be important for protecting hepatocyte function in the presence of high blood ethanol levels.

Animals

Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease.

A jejunal biopsy specimen from an asymptomatic 35 year old man was studied because of a low serum titre of reticulin antibody and the finding of coeliac disease in his son. In this specimen villous structure was quite normal as was the total number of intraepithelial lymphocytes, but the number of gamma/delta T cell receptor bearing lymphocytes was 10 times higher than the mean in control subjects. Two years later a further biopsy specimen was obtained because of clinical symptoms and an increased titre of reticulin antibody. This specimen showed villous atrophy with crypt hyperplasia and increased infiltration of intraepithelial lymphocytes compatible with coeliac disease. A control biopsy specimen taken during gluten free diet showed normalisation of the villous architecture. Latent coeliac disease may be characterised by an increase in gamma/delta positive cells similar to that seen in established coeliac disease.

Adult

Quality of life of patients with sarcoma postchemotherapy.

This study was designed to describe the effects of a 96-hour doxorubicin hydrochloride/dacarbazine chemotherapy protocol for soft-tissue sarcoma on patients' functioning, life-style, and quality of life (QOL). Patients from the surgical oncology clinic of a large, midwestern university completed the Quality of Life Index--Cancer Version (QLI) and Functional Living Index: Cancer (FLIC). Additional information obtained regarded response to chemotherapy and demographic data. Patients were most satisfied with faith in God, family health, health care, long life, and their spouse. Patients were least satisfied with sex life, stress or worries, unemployment, financial independence, and government influence. QOL in the family domain was found to be significantly higher than QOL in the health, functioning, and socioeconomic domains (p less than 0.05). Functional living assessment indicated that patients were confident in their prescribed course of treatment, optimistic about the future, generally felt well, and felt that their QOL had improved since treatment. Aspects of chemotherapy that most interfered with patients' lives were the length of treatment and the financial burden. The patients reported a high confidence level in the medical and nursing care that they received.

Activities of Daily Living

Middle nurse manager effectiveness.

In a nationwide survey of academic health center chief nurse executives (CNEs) and middle nurse managers (MNMs), human management skill was ranked as the most important criterion of effectiveness. The characteristic of flexibility/negotiation/compromise was second. Neither group reported fiscal management skills as a top priority for MNM effectiveness. The authors compare the results with earlier studies of the effectiveness criteria of CNEs, for whom human management skills were ranked second and general management skills first.

Academic Medical Centers

[Juvenile chronic arthritis. A clinical and radiographic study of the chewing apparatus].

The present investigation of a relatively large Danish sample of patients with Juvenile Chronic Arthritis (JCA) revealed high frequencies of symptoms from the masticatory apparatus. 63% of the patients had destructive changes in the region of the mandibular condyles caused by arthritis. In one third of these cases the destructions were severe. Three fourth of the patients with TMJ-affection showed bilateral affection, and one fourth had unilateral affection. TMJ-affection was positively correlated to the duration and the severity of the general disease at the time of examination. Fifty per cent of the patients with TMJ-affection had reduced mouth opening capacity and most of these patients were aware of the problem themselves. The frequency of other symptoms from the TMJ and the jaw musculature was relatively high in the patient group. However, there were no significant differences between these frequencies when the group with TMJ-affection was compared to the group without TMJ-affection except for mouth opening capacity. The patients with TMJ-affection had significantly higher frequencies of frontal and lateral open bite and midline devition when compared to the patients without TMJ-affection. Furthermore, the patients with TMJ-affection had a significantly higher frequency of crowding in the mandibular incisor region than the patients without TMJ-affection. Thus, the study showed that TMJ-affection is common among children with juvenile chronic arthritis, and that the TMJ-affection may result in both functional problems and malocclusion.

Arthritis, Juvenile

Normal small bowel biopsy followed by coeliac disease.

We report four patients (two children, one adolescent, and one adult) having normal small bowel mucosa shown on a biopsy specimen taken before the initial diagnosis of coeliac disease was made. The first biopsy was undertaken in two cases because of suspected malabsorption, in the third because of suspected dermatitis herpetiformis, and in the fourth as part of a coeliac disease family study. After a further 2.6 to 9 years on a diet containing gluten, small bowel villous atrophy with crypt hyperplasia compatible with coeliac disease was found on a second biopsy specimen. The HLA type of the patients was that typical for coeliac disease; all were DR3 positive. Within the families three other patients with coeliac disease have been diagnosed, two earlier and one at the time the first biopsy was undertaken. Four other HLA-DR3 positive haploidentical first degree relatives were found and had biopsies. All four had normal small bowel villous architecture, one had an increased intraepithelial cell count, and another was positive for reticulin and endomysium antibodies. Coeliac disease may exist latent in patients having normal mucosa when eating a normal diet containing gluten.

Adult

Perspectives on the interpretation of continuous mixed venous oxygen saturation.

Continuous measurement of mixed venous oxygen saturation (SvO2) is a beneficial method for evaluating overall dynamic tissue oxygen balance in critically ill patients. Several important factors, however, may influence the accurate analysis of SvO2 data trends. In this review we highlight these factors and support cautious interpretation of SvO2 in conjunction with other available patient data and with strict attention to the clinical value and limitations of the parameter.

Blood Volume

Electrocardiographic response to ice water ingestion.

To determine the necessity of restricting ice water for patients with acute myocardial infarction (MI) we performed studies in 89 patients who had been admitted to a coronary care unit with a diagnosis of acute MI or "rule out MI." Using a split-plot factorial repeated-measures design, we randomly assigned patients to position and sequence of volume. A Marquette Augmented Cardiograph was used to obtain 12-lead electrocardiogram (ECGs) at baseline and at 3, 10, and 25 minutes after ingestion of 200 or 400 ml ice water. Multivariate analysis of variance (MANOVA) was used to assess the significance of each factor alone and in interaction for both ST segments and T waves for 11 leads. The preliminary analysis of variance showed significant difference (p less than 0.10) in ST segments for position in several leads and in T waves for disease in several leads. Differences did not continue to be significant when they were considered across the four time periods (MANOVA); then time and volume were the significant variables for most leads. Mean change scores for ST segment (0.01 to 0.05) and T wave amplitude (0.01 to 0.88) were not clinically significant; however, a few patients had significant changes in ST segment of greater than 1 mm and T wave amplitude of greater than 10 mm. A few patients exhibited T wave inversion, suggesting a third level of significance: clinically detectable differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Urine cytology as a supplement to cystoscopy and biopsy in the control of bladder tumors].

Throughout the years several investigations have either recommended or discredited exfoliative urine cytology because of high incidence of false negative or false positive results. Most authors agree that high grade bladder tumors are diagnosed with fairly high certainty (80-87%) by using exfoliative urine cytology whereas the value of urine cytology of low grade bladder tumors is uncertain. This investigation, including 200 patients who came for cystoscopic control of bladder tumors, revealed 87% accordance between cystoscopic biopsy and exfoliative urine cytology of high grade tumors while there were 47% false negative and no false positive of low grade tumors. On this background, it must be concluded that exfoliative urine cytology is an important investigation in diagnosing and controlling patients with bladder tumors, but the method can not always stand alone.

Aged

Immobility and bone loss in the aging adult.

Increasing numbers of older patients will be admitted to critical care units. Although bone loss will not be the primary concern, astute critical care nurses must be aware that the bone loss associated with immobility, compounded with the bone loss that occurs with aging, can place a patient at the fracture threshold.

Aged

Measuring physical activity in midlife women.

Women's risks for osteoporosis and cardiovascular disease are increasing. Although it is known that these risks decline with physical activity, it is difficult to associate specific risk levels with specific activity levels. Measuring activity levels is complex and problematic, especially in women. The present study explored the validity of a particular measure, the retrospective survey questionnaire, used with a female population to gauge physical activity, both occupational and leisure. To measure construct validity, four retrospective measures were administered to a sample of 43 middle-aged women representing three occupational groups (teachers, clerical workers, nurses) known to differ in activity levels. In addition, measurement approaches were triangulated by including a prospective measure, a beeper-cued record kept by subjects. A significant difference was noted among the groups on retrospective and prospective occupational activity measures, with clerical workers having the lowest levels of energy expenditure. The retrospective occupational measure correlated positively and significantly with the beeper-cued record kept during work; however, no correlation was found between the retrospective leisure measure and the beeper-cued record. These data suggest that the retrospective measure is appropriate for measuring the occupational dimension of physical activity. Additional study is required to identify women's leisure pursuits and the dimension of their household activities.

Adult