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Biomedical subjects

M Norman

Publications and source records attributed to M Norman.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

Proteoglycan metabolism in the connective tissue of pregnant and non-pregnant human cervix. An in vitro study.

Profound changes occur in the cervix during pregnancy. In particular, the connective tissue is remodelled. To elucidate the mechanisms behind this process, the metabolism of cervical connective tissue was studied using tissue cultures. Cervical biopsies from non-pregnant and pregnant women were incubated with [35S]sulphate. The proteoglycans of the tissue specimens were purified by ion-exchange and gel chromatography and characterized by SDS/PAGE and by enzymic degradation. In the non-pregnant cervix, the incorporation of [35S]sulphate into the proteoglycans was linear for 48 h. During the first 6 h of incubation the accumulation of chiefly one small labelled proteoglycan (apparent Mr 110,000) substituted with dermatan sulphate was recorded. This is in accordance with the known proteoglycan composition of non-pregnant cervical tissue. In addition, small amounts of two larger radioactive dermatan/chondroitin sulphate proteoglycans (apparent Mr values 220,000 and greater than 500,000) were recorded. After longer periods of incubation the proportion of heparan sulphate proteoglycans increased considerably. The pregnant tissue showed a clearly different composition of labelled proteoglycans. An increased accumulation of the two larger dermatan/chondroitin sulphate proteoglycans was seen in addition to the dominant small dermatan sulphate proteoglycan of the non-pregnant cervix. The rate of accumulation of these two proteoglycans was about 3 times higher in the pregnant tissue, whereas that of the small dermatan sulphate proteoglycan was only increased 2-fold. The fact that the concentration of proteoglycans in the pregnant cervix is approximately one-half of that in the non-pregnant cervix indicates that the turnover of proteoglycans in pregnant cervical tissue is significantly increased. The major effect of this profound change of metabolism was a 50% decrease in proteoglycan content and a 2-fold increased proportion of a dermatan sulphate proteoglycan with an apparent Mr of 220,000.

Adult↗
PubMed1991

Reactive hyperemia in term neonates and adults--a laser Doppler fluxmetry study of skin microcirculation.

The reactivities of neonatal and adult microcirculation have been studied and compared. The cutaneous reactive hyperemia after 1 and 4 min of arterial occlusion (AO) was measured with a laser-Doppler fluxmeter in 21 healthy neonates and 10 adults. Local skin temperature, mean arterial blood pressure (MAP), and skin prick hematocrit were also determined at the same time. The magnitude of neonatal reactive hyperemia was approximately one-third that of the adult response regardless of the duration of AO. In both groups, with age-specific regressions, the hyperemic blood flow response after 4 min of AO developed more slowly in subjects with low MAP and was of low magnitude in subjects with high hematocrit values. In response to a prolongation of AO, from 1 to 4 min, the magnitude and duration of hyperemia increased significantly and similarly in both neonates and adults. We conclude that compared to adults neonates have a less pronounced ability to increase skin microcirculation in response to local ischemia. The normally low blood pressure and high hematocrit in newborn infants contribute further to this conclusion.

Adult↗
PubMed1991

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↗
PubMed1991

Acute confusion--an unusual form of cerebral herpes simplex virus infection?

Herpes simplex virus (HSV) infections are common and, if afflicting the central nervous system, may cause death or severe sequelae. Since specific therapy is now available there is an increasing demand for the recognition of the various ways in which cerebral HSV-infections may be manifested. This report describes a 15-year-old boy who presented acutely with mental symptoms of confusion, hallucinations and sleep disturbance. Simultaneously, but without any increase in cerebrospinal fluid cell or protein content, an intrathecal production of HSV-antibodies of transient nature was detected. These findings suggest that the patient may have suffered from an unusual form of herpes infection in the central nervous system. We suggest that similar cases should be thoroughly explored for possible herpes etiology as early as possible during the acute phase of the disease.

Adolescent↗
PubMed1990

Blood lead, calcium status, and behavior in preschool children.

To determine if calcium status is associated with blood lead levels and behavior, 64 black urban children aged 18 to 47 months were studied. Twenty-seven controls (blood lead levels, less than 1.45 mumol/L) were compared with 37 cases (blood lead levels, greater than or equal to 1.45 mumol/L) with respect to four calcium measures (calcium intake, serum calcium level, 1,25-dihydroxyvitamin D level, and bone densitometric findings) and three behavioral scores. Levels of 25-hydroxyvitamin D provided a measure of vitamin D sufficiency. As expected, blood lead level was associated with pica scores. However, none of the calcium measures differed between cases and controls. Controlling for four confounders (season, pica score, maternal education, and sex), yielded no significant differences between the two groups in the mean values of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D level. There was no interaction between blood lead level and the four covariates. No relationship could be demonstrated between calcium status and the pica scores.

Bone Density↗
PubMed1990

Antigenic stability of fimbriae of Bacteroides nodosus.

Successful vaccination of sheep against footrot and attempts to eradicate the disease depend on there being a limit to the antigenic diversity of the causative bacterium, Bacteroides nodosus. Fimbrial antigenic variation was therefore investigated in vivo, both under conditions of chronic infection and under the pressure of a vaccine-induced immune response, to ascertain whether this represented an obstacle to such goals. Material was available from 5 experiments and although B. nodosus appeared to have undergone changes in its fimbrial antigens in one of these, the possibility that superinfection was responsible for the variation detected could not be ruled out because all sheep in this case were maintained at pasture. Overall, the results provided no evidence of fimbrial antigenic shift in B. nodosus in vivo and in conclusion, the survival of the organism in the sheep's foot, both in long-term natural infection and following vaccination, must therefore be related to factors other than the ability to undergo antigenic variation in order to evade the host's immune response.

Animals↗
PubMed1990

The proportion of glycosylated prolactin in serum is decreased in hyperprolactinemic states.

The proportion of serum PRL that is glycosylated has been determined, and the effects of physiological and pathological hyperprolactinaemia on this proportion have been examined. Glycosylated and nonglycosylated PRL were immunoprecipitated from serum and subjected to polyacrylamide gel electrophoresis under reducing and dissociating conditions. Separated proteins were then transferred to nitrocellulose paper by electroblotting and detected immunologically with anti-PRL antiserum and 125I-labeled protein-A, followed by autoradiography. The proportion of total monomeric PRL present in the glycosylated form was then estimated by densitometric scanning of autoradiograms. In normal individuals glycosylated PRL was predominant, accounting for about 72% of the circulating monomeric PRL. This proportion was markedly decreased (ranging from undetectable to about 60%) in the serum of women who were pregnant or were lactating postpartum and also in patients with hyperprolactinemia caused by a pituitary tumor. The results suggest that under basal conditions the majority of PRL secreted from the pituitary is glycosylated, but with physiological or pathological hyperprolactinemia the capacity for glycosylation is exceeded.

Adult↗
PubMed1989

A comparison between the composition of maternal peripheral plasma and plasma collected from the retroplacental compartment at caesarean section. A study on protein and steroid hormones and binding proteins.

In the pregnant uterus unique immunological conditions must prevail. Since compounds of possible fetoplacental origin may modulate the local maternal immunological response, higher concentrations of such compounds in the vicinity of the conceptus might be expected. We have measured the concentrations of several compounds in peripheral and retroplacental plasma, mainly by immunological methods, from women delivered by caesarean section in pregnancy week 38-40. Significantly higher (P less than 0.001) retroplacental concentrations were found for human placental lactogen, prolactin, alpha-fetoprotein, tissue polypeptide antigen, non-conjugated estriol and progesterone. Peripheral plasma levels were significantly higher for cortisol (P less than 0.01), transcortin (P less than 0.001) and sex-hormone binding globulin (P less than 0.002). No difference was found for albumin, alpha 2-macroglobulin, estradiol, placental alkaline phosphatase and human chorionic gonadotrophin. Significant correlations between retroplacental and maternal peripheral plasma levels were found for progesterone, cortisol, estradiol, estriol, transcortin, sex-hormone binding globulin, prolactin, human placental lactogen, human chorionic gonadotrophin, placental alkaline phosphatase, albumin and alpha 2-macroglobulin. There were also significant correlations between estradiol and sex-hormone binding globulin as well as transcortin in peripheral maternal plasma.

Adult↗
PubMed1988

Capillary blood cell velocity in full-term infants as determined in skin by videophotometric microscopy.

In order to study the neonatal microcirculation, the capillary hemodynamics in skin was investigated in 43 full-term infants 2-7 days after birth. The nailfold capillaries of the thumb were visualized by means of television microscopy and the capillary blood cell velocity (CBV) was videophotometrically quantified in 107 microvessels. The skin temperature, mean arterial blood pressure, and heel puncture hematocrit were measured simultaneously to evaluate any relation with the CBV. The mean CBV in all infants was 0.38 +/- 0.21 mm/s, with a range of 0.04 to 1.2 mm/s in individual capillaries. There was no correlation between CBV and skin temperature (27-33 degrees C), mean arterial blood pressure (44-68 mm Hg), or postnatal age. However, a significant correlation was found between the log CBV and the skin prick hematocrit (r = -0.64, p less than 0.001). It is concluded that the mean CBV during the 1st wk of life is not significantly different from the capillary velocity reported in adults. Normal variations in skin temperature and mean arterial blood pressure, as well as age differences 2-7 days after birth, do not significantly influence the neonatal skin capillary blood flow. However, the hematocrit is of major importance for skin capillary perfusion in the newborn infant.

Blood Flow Velocity↗
PubMed1988

Bioactivity and immunoactivity of growth hormone during dynamic testing of patients with acromegaly.

We have used the Nb2 cell proliferation bioassay for lactogenic hormones to investigate the biological activity of hGH in sera of patients with acromegaly. The specificity of the assay has been improved by the use of monoclonal antibodies to block the activity of individual lactogenic hormones. Disease activity in patients was assessed by scoring signs and symptoms, and by measuring IGF-I concentrations in some patients. Patients with a wide spectrum of disease activity were studied using a TRH test. hGH concentrations were measured by bioassay, RIA and immunoradiometric assay (IRMA) at 0, 20 and 60 min after injection of TRH. There was a high degree of correlation between log10 of all hGH concentrations measured by bioassay and RIA (r = 0.995, P less than 0.0001), between bioassay and IRMA (r = 0.990, P less than 0.0001), and between RIA and IRMA (r = 0.995, P less than 0.0001). In contrast to previous reports, we found no evidence for changes in the bioactivity of hGH secreted after pituitary stimulation.

Acromegaly↗
PubMed1987

Protection of sheep against footrot with a recombinant DNA-based fimbrial vaccine.

Recombinant Pseudomonas aeruginosa cells containing the Bacteroides nodosus fimbrial subunit gene under the transcriptional control of a strong promoter produce large amounts of B. nodosus-type fimbriae. We have carried out vaccination trials which show that these fimbriae are just as effective as either natural fimbriae or whole cell preparations of B. nodosus in inducing protective immunity against homologous footrot challenge. The recombinant-produced fimbriae are also effective therapeutically in accelerating the rate of healing of pre-existing footrot lesions. These results confirm that the structural subunit of the fimbrial strand is a primary protective antigen against footrot, and demonstrate the practicality and potential of recombinant DNA approaches to the development of new vaccines against B. nodosus and other Type 4 fimbriate pathogens.

Animals↗