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Biomedical subjects

M Norman

Publications and source records attributed to M Norman.

At least 19 recordsLinked to original sources

An evaluation of skin capillary blood flow determinations in neonates using a computerized videophotometric method.

Dynamic capillaroscopy has been shown to give valid measurements of skin capillary blood flow in adults. The aim of this investigation is to evaluate the accuracy of the method when applied to studies in newborn infants. A computerized videophotometric technique was used to measure the skin capillary blood cell velocity (CBV) and the capillary erythrocyte column diameter at 64 standardized locations in 16 nailfold capillaries in five subjects. To estimate the method's reliability, we calculated the coefficient of variation (CV = 1 SD/mean x 100%) for repeated measurements at each location. The CV for CBV determinations was found to be 3.4% (0.9-13%) and the corresponding value for capillary diameter measurements was 6.7% (0.5-12%) (median and range). Although the CBV and diameter values were found to vary along the course of the capillary, the volume flow of blood cells was assumed to be the same in simultaneously studied but different sections of the capillary. The paired CBV and diameter observations were therefore used to calculate blood cell flow values at an average of four different intracapillary locations. To estimate the method's validity, the CV for these repeated flow calculations was determined and found to be 7.5% (3.2-26%). We conclude that the age-specific characteristics in neonates, mainly a high hematocrit and short, irregular skin capillary loops, do not limit the feasibility and accuracy of videophotometric microscopy for dynamic microcirculatory studies in neonates.

Capillaries

Effects of neonatal polycythemia and hemodilution on capillary perfusion.

The effects of neonatal polycythemia on nutritive capillary perfusion were investigated by a television microscopy technique. The capillary blood flow velocity in skin was measured in 12 neonates with polycythemia before and after treatment with hemodilution, and in 13 healthy control infants. The capillary blood flow velocity in the patients was 0.11 (0.02 to 0.34) mm/sec and in the healthy control infants 0.30 (0.17 to 0.44) mm/sec (p less than 0.01, median and range values). In relation to the absolute hematocrit change after treatment range, -20% to 0%), the capillary blood flow velocity increased nonlinearly (range, +733% to -14%; r = -0.98; p less than 0.001). The postnatal age was found to contribute significantly to the variation in results--the neonates with polycythemia studied during the first day of life had a very slow skin capillary circulation and responded to treatment with a more pronounced increase in capillary blood flow velocity than did the older patients. This in vivo model for capillary perfusion indicates that an insufficient microcirculation may be involved in the pathophysiology responsible for the morbidity associated with neonatal polycythemia.

Age Factors

Alanine-scanning mutagenesis of human prolactin: importance of the 58-74 region for bioactivity.

We have generated 10 alanine mutants of human PRL (hPRL), a member of the PRL/GH family, to investigate the involvement of the highly conserved 58-74 region in the biological behavior of the protein. When treated with polyclonal anti-hPRL antibodies, all mutants were immunologically indistinguishable from the unmodified hPRL, and circular dichroism analyses indicated that their alpha-helix content was similar to that of the unmodified hormone. Mutations C58A, K69A, and, to a lesser extent, P66A affected drastically the ability of hPRL first to bind to the lactogenic receptor and second to stimulate the proliferation of Nb2 lymphoma cells, proving the importance of the 58-74 peptide segment for hPRL bioactivity. Binding affinities of these mutants to the Nb2 lactogenic receptor have been compared to lactogenic binding data previously obtained for several mutants of hGH. The comparison reveals that the residues involved in the biological properties of the two proteins are not at topologically equivalent positions. Hence, we suggest that the binding of these hormones to the lactogenic receptors occurs through a different molecular mechanism having distinct requirements at the residue level.

Alanine

Growth hormone binding protein in patients with renal failure.

To investigate changes in the growth hormone binding protein (GH-BP) in renal disease, gel chromatography was used to separate free and bound hormone after incubation with 125I-GH, the results being expressed as a percentage of radioactive GH eluting in a high molecular weight (70-80 kD) peak. In 26 normal individuals, binding was 39.3 +/- 8.0%, while in 11 patients with renal disease who were off dialysis binding was reduced to 16.8 +/- 5.6%. Similarly, in 9 patients undergoing hemodialysis binding was reduced to 24.6 +/- 6.8%, in 8 patients undergoing chronic ambulatory peritoneal dialysis binding was reduced to 25.7 +/- 7.6%, and in 9 patients within three months of a renal transplant binding was reduced to 25.1 +/- 8.6%. Scatchard analysis showed that these changes were not a result of decreased affinity of GH-BP for GH, and receptor binding studies showed that uremic serum was not inhibiting binding. The decreased concentration of GH-BP may indicate decreased expression of the GH receptor in target tissues, and hence diminished responsiveness to GH in renal failure.

Adult

Preinductive cervical ripening with prostaglandin E2 in women with one previous cesarean section.

Thirty term pregnant women with one previous cesarean section and with unripe cervices were given 0.5 mg prostaglandin E2 in gel strictly intracervically for cervical ripening and labor induction. Fifteen out of these 30 women (50%) were vaginally delivered within 24 hours. The cervical ripening/labor induction was considered a failure in two women. In one woman, an episode of hypercontractility was registered. After tocolytic therapy the uterine activity was normalised and the woman had a normal vaginal delivery. The frequency of cesarean sections was 8/30 (27%). At the operations no insufficiencies in the uterine scars were noted. Conclusively, strict intracervical application of 0.5 mg prostaglandin E2 in gel can be used for cervical ripening and labor induction also in women with one previous cesarean section.

Administration, Intravaginal

Levels of GH binding activity, IGFBP-1, insulin, blood glucose and cortisol in intensive care patients.

OBJECTIVE: To investigate levels of serum GH binding activity, insulin-like growth factor binding protein-1 (IGFBP-1), blood glucose, serum insulin, and cortisol in patients on the Intensive Therapy Unit. DESIGN: Case-control study of severely ill patients admitted to the Intensive Therapy Unit. PATIENTS: Six critically ill patients (51-78 years) who required ventilatory and nutritional support and six healthy age, sex, height and weight matched controls. MEASUREMENTS: Patients and controls were studied for two 24-hour periods; the patients before and after commencing parenteral nutrition, the controls whilst fasted and on a second occasion when fed a diet equal in protein and calories to that of the patients' parenteral nutrition. Samples were taken hourly for measurement of IGFBP-1, blood glucose, serum insulin and cortisol. Growth hormone binding activity was measured at 0 hours. RESULTS: Blood glucose levels were higher in the patients than controls in both the fasted (mean +/- SEM 5.1 +/- 0.5 vs 3.8 +/- 0.2 mmol/l, P = 0.04) and fed states (10.1 +/- 1.6 vs 5.0 +/- 0.1 mmol/l, P = 0.02) and patients' insulin levels were also higher when fed (81.5 +/- 31.6 vs 24.2 +/- 4.8 mU/l, P = 0.046) although there were no significant differences between patients and controls when fasted. IGFBP-1 levels were inversely related to insulin levels in both the patients and controls; mean IGFBP-1 concentrations were higher in fasted patients than in controls (123 +/- 38 vs 52 +/- 9, P = 0.046) but when fed, both groups had similar mean levels. Serum GH binding activity was low in the patients and did not change with feeding. Mean 24-hour cortisol levels were higher in the patients than in controls, whether fasted or fed, and showed no nyctohemeral rhythm. CONCLUSIONS: We have previously reported that critically ill patients have low levels of IGF-I with augmented basal levels of GH. The present results demonstrate that these changes in the GH-IGF-I axis are associated with insulin resistance with respect to blood glucose and high levels of IGFBP-1 when patients are fasted. However, when fed, the inverse relationship of IGFBP-1 to insulin is preserved. Patients have low levels of GH binding activity and increased mean cortisol levels. Interventional studies in this patient group with GH and IGF-I must take account of these changes in binding protein and cortisol levels.

Abdomen

Further characterization and biologic activity of ragweed antigen--induced neutrophil chemotactic activity in man.

We have previously described the appearance in serum of increased neutrophil chemotactic activity (NCA) during bronchospasm induced by inhalation of ragweed antigen in ragweed-sensitive subjects. This NCA is non-complement derived, appears within 1 min after antigen inhalation, and is not seen after methacholine-induced bronchospasm. This article describes further characterization of this chemotactic activity and correlation with in vivo leukocytosis. NCA consistently eluted in the void volume (fraction I) after Sephadex G-150 chromatography of patient serum obtained 10 min postchallenge. Fraction I contained 94% of the NCA of postchallenge whole serum. Both postchallenge whole serum and fraction I deactivated neutrophils to autologous chemoattractants and complement-derived chemotactic factors, but not serum-independent chemotactic factors. NCA was chemotactic for neither human nor guinea pig eosinophils, nor for human mononuclear cells. A significant increase of circulating neutrophils was seen only after antigen-induced bronchospasm and correlated with the increase in NCA. Thus, NCA represents another inflammatory mediator of probable mast cell origin that may explain, at least partially, the accumulation of neutrophils observed in the peripheral blood, skin, and bronchial wall after immediate hypersensitivity reactions.

Bronchial Provocation Tests

Release of neutrophil chemotactic activity during immediate hypersensitivity reactions in humans.

Heat-stable, serum-derived chemotactic activity for neutrophils is shown in a human model of immunoglobulin E-mediated asthma. Twenty-six ragweed-sensitive subjects underwent bronchial provocation challenge using ragweed and Mecholyl. Increased neutrophil chemotactic activity was found in serum tested from 5 to 30 min after a positive ragweed-inhalation challenge, but not after negative ragweed challenge. The appearance of neutrophil chemotactic activity did not reflect the effects of bronchospasm alone, because it was not found after bronchospastic responses to Mecholyl in the same subjects. There were no accompanying changes of serum complement activity, nor evidence of inhibition of the chemotactic activity by proir exposure to antisera to the third and fifth components of complement. Ultrafiltration of serum showed chemotactic activity contained in fractions of at least 50 000 daltons. This appears to be the first demonstration of neutrophil chemotactic activity liberated during experimentally induced immunoglobulin E-mediated asthma in humans.

Adult

The cost and advantages of establishing an age-sex register.

The advantages and disadvantages of different methods of creating an age-sex register are described. The cost of setting up such a register in a NHS practice with 10,000 patients is shown, and it is suggested that financial advantages may cover the costs involved.

Costs and Cost Analysis

Grief and mourning.

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Community Health Nursing

Bacteremia on an obstetric-gynecologic service.

In a one-year evaluation of the Obstetric-Gynecologic Services of the Los Angeles County University of Southern California Medical Center, bacteremia was confirmed on 144 occasions in 139 patients. This represented an over-all incidence of 7/1,000 admissions with gram-negative bacteremia observed in 3.1/1,000 admissions. There were four deaths in this series. The most frequently recovered aerobes were Escherichia coli, enterococci, and beta hemolytic streptococci, not Group A or D, while the most commonly isolated anaerobes were peptostreptococci, peptococci, and Bacteroides. These patterns of bacterial isolation should be acknowledged in antibiotic strategies for septic patients. There is a positive correlation between the incidence of intrapartum maternal and fetal monitoring and postpartum maternal bacteremia. The oncology patients were the most seriously ill women with bacteremia.

Adolescent

Antimyelin antibodies in neurologic diseases. Immunofluorescent demonstration.

Antimyelin binding activity was determined in patients with multiple sclerosis, amyotrophic lateral sclerosis, other neurologic diseases, and normals. There was an increase in the group mean titer of antimyelin antibodies in patients with multiple sclerosis (MS) in acute exacerbation, amyotrophic lateral sclerosis (ALS) and Guillain-Barré syndrome. A lesser degree of binding was found in normals of all ages. There was an increase in the incidence of antimyelin antibodies in the IgM class in patients with ALS and MS. The interaction between human immunoglobulins and myelin seems to be immunologically specific and has the nature of an antigen-antibody reaction.

Acute Disease