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Biomedical subjects

N Modi

Publications and source records attributed to N Modi.

At least 19 recordsLinked to original sources

Atrial natriuretic peptide, cyclic guanosine monophosphate and sodium excretion during postnatal adaptation in male infants below 34 weeks gestation with severe respiratory distress syndrome.

The role of atrial natriuretic peptide (ANP), in the perinatal period, is at present unclear. In adults urinary cyclic guanosine monophosphate (cGMP) is considered an index of the biological activity of plasma ANP. The aim of this study was to determine the relationship between plasma ANP, cGMP excretion (cGMPex) and sodium excretion (Naex) in preterm infants in the first days after birth. Sequential, 4 hourly, measurements of plasma ANP, cGMPex and Naex were made in 12 male neonates of median gestational age 27 weeks (range 25-33) and median birth weight 0.981 kg (range 0.635-2.029) over a median period of 5.2 days (range 2.3-10). The ratios of cGMPex to ANP and of Naex to cGMPex were each plotted against postnatal age. The ratio of cGMPex to ANP increased ten fold in the first 3-4 days after birth but then remained relatively constant; the ratio of Naex to cGMPex showed a steady increase from birth. We conclude that, in extremely immature infants, renal sodium loss in response to cGMP increases rapidly during the first 10 days after birth. In addition, after 3-4 days from birth, plasma ANP ia associated with a constant proportionate rate of cGMP excretion though, as the plateau ratio of cGMPex to ANP varied widely between babies, cGMPex cannot be used to predict plasma ANP in cross sectional studies. These changes may reflect postnatal adaptation and/or maturation of both ANP receptors and cGMP mediated cascades. In the immediate postnatal period, plasma ANP may also have a non-renal role.

Age Factors

The effect of polycythemia and hypoxia on urinary N-acetyl-beta-D-glucosaminidase activity in newborns.

Urinary N-acetyl-beta-D-glucosaminidase activity was assayed in fullterm and preterm polycythemic neonates, in preterm infants with hypoxia, and in healthy newborns. There were no significant differences between fullterm and preterm babies or between appropriate for gestational age and small for gestational age neonates in the normal group. N-acetyl-beta-D-glucosaminidase excretion on the first day of life was significantly raised in polycythemic newborns (P less than 0.01). Fourteen days after partial plasma exchange the enzyme activity returned to normal. N-acetyl-beta-D-glucosaminidase activities in preterm babies with respiratory distress syndrome were significantly (P less than 0.01) raised on the 1st, 2nd, 4th days and fell sharply to the 14th day. N-acetyl-beta-D-glucosaminidase isoenzyme studies revealed that urine samples taken from preterm babies with respiratory distress syndrome in the first week after birth contained increased amounts of intermediate and B isoenzyme forms while there was a concomitant reduction in the amount of the A form present.

Acetylglucosaminidase

The influence of postnatal respiratory adaptation on sodium handling in preterm neonates.

The relationship between sodium handling and alveolar-arterial oxygen gradient (AaDO2) was studied in 26 preterm babies requiring ventilation from birth. The difference between sodium intake and urinary sodium excretion was determined in sequential, four hourly periods throughout the course of the respiratory illness. Sodium retention changed from positive (mean 1.42 mmol kg-1 day-1) during the phase of deteriorating respiratory function to negative (mean - 1.99 mmol kg-1 day-1) during improving respiratory function. This difference is highly significant (P less than 0.001). A temporal relationship is also shown, in the form of individual time plots of AaDO2 and sodium retention for each baby; changes in sodium handling parallel changes in AaDO2. The diuresis that accompanies improving respiratory function is characterised as a natriuresis, with free water clearance remaining unchanged before and after the point of improvement. We suggest that a primary change in sodium handling, triggered by postnatal respiratory adaptation, may initiate the contraction in extracellular fluid volume that characterises early postnatal existence.

Adaptation, Physiological

Urinary creatinine excretion and estimation of muscle mass in infants of 25-34 weeks gestation.

The urinary excretion rate of creatinine was measured over 89 days in 31 infants of gestational ages 25-34 weeks in the first week of life. Creatinine excretion was shown to have a significant positive correlation with weight and postconceptional age. Creatinine excretion factored by body weight was also positively correlated with weight and postconceptional age. Pooled analysis of published data together with our own, confirms that this correlation is important. Muscle mass was estimated from creatinine excretion rate. A regression equation was derived predicting muscle mass from birth-weight and gestational age. Muscle mass increases from 12% of birthweight at 25 weeks gestation to 19% at 34 weeks and 24% at 40 weeks. This is in agreement with classic dissection studies which showed muscle mass to be 25% of body weight at term.

Birth Weight

Phototherapy and the use of heat shields in very low birthweight infants.

The irradiance produced by phototherapy units in use on a neonatal unit was measured. The phototherapy tubes were found to decline at a variable rate. Heat shields used to decrease heat and evaporative losses in the very low birthweight infant reduce irradiance and may appreciably limit the effectiveness of phototherapy.

Critical Care

Outbreak of cephalosporin resistant Enterobacter cloacae infection in a neonatal intensive care unit.

Enterobacter cloacae resistant to third generation cephalosporins emerged rapidly during an outbreak of serious infections due to this organism in a neonatal intensive care unit where ampicillin and gentamicin were used as first line antibiotic treatment. Organisms resistant to cephalosporins were isolated from 12 infants, six of whom developed systemic infection. Two infants died. Isolates of E. cloacae from four of five infants treated with cefotaxime showed a loss of sensitivity to this antibiotic during treatment, but in the three infants who survived sensitive organisms were again isolated after treatment had stopped. Stopping treatment with the cephalosporins, closure of the unit to new admissions, and strict cohorting of colonised infants resulted in a prompt end to the outbreak. This outbreak suggests that the routine use of third generation cephalosporins for suspected sepsis may be inappropriate in the presence of a large reservoir of organisms with the potential for rapidly developing resistance. Routine bacteriological surveillance, however, might permit their use on a rotational basis.

Cephalosporins

Interdonor incompatibility due to anti-Kell antibody undetectable by automated antibody screening.

A unit of whole donor blood, the plasma of which contained anti-Kell antibody, was transfused into a Kell-negative patient who had received a unit of Kell-positive blood 4 weeks previously. A haemolytic transfusion reaction ensued. The antibody had gone undetected in routine automated screening of the donor blood. Automated antibody detection techniques do not offer reliable detection of anti-Kell antibodies.

Blood Group Antigens

In vitro assays for botulinum toxin and antitoxins.

Clostridium botulinum produces several powerful neuroparalytic toxins which, although rare in food-poisoning instances, are generally fatal. A considerable amount of effort has therefore been made by the food industry to ensure that food treatment processes adequate to prevent growth and toxin production by Cl. botulinum. Laboratory mice and guinea-pigs are presently used extensively both for the assay of botulinum toxins and for the development and assessment of vaccines used to protect laboratory workers. An amplified ELISA, using a monoclonal antibody, has been developed for botulinum type A toxin with a sensitivity similar to that of the mouse acute toxicity test. The immunoassay has been found to be applicable to the detection of toxin in foodstuffs and could replace the currently used mouse bioassay in many laboratories. Immunoassays have also been developed for the detection of antibodies to botulinum toxins. A preliminary study has shown that antibody titres to botulinum types A and B toxins in sera taken from immunised personnel, as measured by ELISA, showed limited correlation with those measured by the toxin neutralisation test in mice. A more extensive study should determine whether the latter test can be replaced by the ELISA.

Animal Testing Alternatives

Monoclonal antibody-based immunoassay for type A Clostridium botulinum toxin is comparable to the mouse bioassay.

A monoclonal antibody (BA11) has been produced against Clostridium botulinum type A neurotoxin by the fusion of myeloma cells (P3 NS1/1-Ag4-1) with spleen cells from BALB/c mice immunized with botulinum type A neurotoxoid. The antibody bound specifically to botulinum type A neurotoxin, showing no cross-reactivity with types B and E botulinum toxins or with any of several other bacterial toxins tested. The monoclonal antibody did not bind to botulinum type A neurotoxin which had been denatured with sodium dodecyl sulfate and bound only weakly to each of the separated heavy and light subunits of the neurotoxin, suggesting a conformational requirement for the antigenic determinant of the antibody. A sensitive immunoassay for C. botulinum type A toxin with monoclonal antibody BA11 in conjunction with an enzyme amplication system has been developed which allows detection of 5 to 10 mouse 50% lethal doses ml-1 of purified neurotoxin. The assay was equally sensitive when applied to the detection of crude toxin in food stuffs; the average value for the minimum level of detectable toxin in extracts of tinned salmon or corned beef was 9 +/- 3.1 mouse 50% lethal doses ml-1.

Animals