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Dopamine (DA), produced in proximal tubular cells, is believed to be an important intrarenal natriuretic hormone. Experimental studies have shown that the natriuretic effect of DA is less pronounced in the fetal kidney. We have evaluated renal DA and norepinephrine (NE) in the neonatal period, using urinary excretion as an indicator of renally produced/released-catecholamines. In very low-birth-weight infants (25-30 weeks gestational age) there was an increase in urinary DA (pmol/mumol urinary creatine) and NE (pmol/mumol urinary creatinine) from 1 to 13 days postnatal age, despite a decrease in sodium excretion. Urinary NE correlated with plasma NE, whereas plasma DA was undetectable. In summary, NE excretion parallels plasma levels and could reflect the general sympathoadrenal activity, whereas DA is primarily of renal origin. Renal DA and NE increase in the first 2 weeks of life in immature infants. We conclude that the catecholamine system of the human kidney undergoes maturational changes postnatally.

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The concentrations of copper (Cu), zinc (Zn) and selenium (Se) in the brain and kidneys of second trimester fetuses (abortion cases) and infants (deceased before three months of age) were determined. Concentrations of Cu in brain, 0.31-1.6 mg/kg wet weight, increased with age, and were, on the average, three times higher in the brains of infants than of fetuses. In kidneys, Cu concentrations ranged between 0.34 and 2.9 mg/kg, and increased with age after birth. Concentrations of Zn in the brain decreased significantly with age in the fetuses, from about 7 mg/kg at post-conceptional week 12 to less than 5 mg/kg at week 20, but increased again postnatally. In kidneys, Zn concentrations (12-37 mg/kg) increased in parallel with the increase in tissue density. Concentrations of Se in brain, 0.072-0.14 mg/kg, decreased with age in the fetuses, but increased with age postnatally. Kidney Se concentrations (0.16-0.55 mg/kg) did not change significantly with age during the fetal period, but increased about 2.5 times during the postnatal period. There was a significant association between the concentrations (on molar basis) of Zn and Cu in kidneys, but not in brain. There was no correlation between the concentrations of Cu, Zn or Se and those of mercury, cadmium and lead, previously determined in the same samples, with the exception of mercury and Se in kidneys.

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The endogenous production of nitric oxide (NO) in the upper airways was studied in healthy newborn infants within the first minutes after delivery (N = 2) and at postnatal ages of 1 and 24 h (N = 13). Measurements were made in infants born vaginally or by cesarean section and at various times after the rupture of membranes. Gas was sampled from the nose and pharynx, and NO concentrations were determined by a fast response chemiluminescence analyzer. Sampling from the nose at a constant flow of 20 mL/min gave 0.27 +/- 0.01 parts per million (mean +/- SEM, ppm) of NO, independent of age and mode of delivery (vaginal delivery and cesarean section). Allowing NO to accumulate in the nose for 15-120 s yielded peak concentrations up to 4.6 ppm. A 30% increase was noted between 1 and 24 h of age. We conclude that nasal peak NO concentrations in the ppm range can be demonstrated in the healthy newborn infant within the first hour after birth. Consequently autoinhalation of endogenously produced upper airway NO may play a role in the adaptation of the respiratory system to postnatal life in the human.

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The concentrations of mercury (Hg), cadmium (Cd) and lead (Pb) in brain (cerebrum) and kidney during fetal (second trimester terminations or abortions, n = 20) and postnatal (infants deceased before three months of age, n = 15) development have been studied. Information on possible sources of exposure was obtained from the mothers of the fetuses, but not from those of the infants. The median concentration of Hg in the brain was 4 micrograms/ kg wet weight in both fetuses and infants (total range < or = 2-23 micrograms/kg). The concentrations of Hg in the kidneys were significantly higher than in brain, median of Hg 6 micrograms/kg (range < or = 5-34 micrograms/kg) in fetuses and 10 micrograms/kg (< or = 7-37) in infants. There was a tendency of increasing concentration of Hg in the fetal kidney, but not in the brain, with increasing number of amalgam fillings in the mothers. The concentration of Cd in the brain was less than 1 microgram/kg in most cases, both in fetuses and infants. The concentration of Cd in the kidneys was significantly higher, with a median of about 2 micrograms/kg (1-8 micrograms/kg) in both groups. There was no detectable association between tissue Cd concentrations and the smoking habits of the mothers. The concentration of Pb in brain was below 10 micrograms/kg in most cases. In the kidneys, the concentrations of Pb were significantly higher, with a median of 12 micrograms/kg in the fetuses (range < or = 6-20 micrograms/kg) and 15 micrograms/kg (< or = 9-36 micrograms/kg) in the infants. In general, the concentrations of Cd and Pb were lower than in previously reported studies.

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We have isolated a human homolog of Xenopus Eg5, a kinesin-related motor protein implicated in the assembly and dynamics of the mitotic spindle. We report that microinjection of antibodies against human Eg5 (HsEg5) blocks centrosome migration and causes HeLa cells to arrest in mitosis with monoastral microtubule arrays. Furthermore, an evolutionarily conserved cdc2 phosphorylation site (Thr-927) in HsEg5 is phosphorylated specifically during mitosis in HeLa cells and by p34cdc2/cyclin B in vitro. Mutation of Thr-927 to nonphosphorylatable residues prevents HsEg5 from binding to centrosomes, indicating that phosphorylation controls the association of this motor with the spindle apparatus. These results indicate that HsEg5 is required for establishing a bipolar spindle and that p34cdc2 protein kinase directly regulates its localization.

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A review of the daily requirements of sodium, potassium and chloride in preterm infants with particular emphasis on very low-birth-weight (VLBW) infants is given against the background of our present knowledge of the homeostatic regulation of these electrolytes during early postnatal life. Particular attention has been given to the importance of balanced fluid and electrolyte homeostasis in the control of compartment volumes and tonicity. The risk of rapid changes of extracellular fluid osmolality for many organs, and particularly for the brain, has been stressed. In order to obtain an adequate sodium and fluid balance during the first postnatal weeks in preterm infants of varying gestational age, recommendations for sodium intake during the first 4-5 postnatal weeks are given.

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At St. Göran's Children's Hospital (a tertiary center), we perform electron microscopy of feces in most cases of nosocomial gastroenteritis. From September 1987 through April 1992 we identified 32 episodes of calicivirus infection, 25 of which were nosocomial and, except for one outbreak, sporadic. Systematic study of the nosocomial outbreak of calicivirus gastroenteritis from November 1991 to January 1992, revealed calicivirus in the stools of 8 of 23 children with diarrhea and 0 of 10 without diarrhea. In 3 of 7 sampled after cessation of diarrhea, calicivirus excretion continued for 3 to 6 days. We found no calicivirus in 42 staff members or 9 members of infected patients' families. Nosocomial transmission of calicivirus can occur among infants.

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Numerous clinical studies during the past two decades have indicated that kidney function and regulation of electrolyte and fluid balance undergo profound changes in the neonatal period. The genetic mechanisms behind these developmental changes have recently been the topic for many investigations and has led to the identification of factors, reviewed here, that seem to be of extraordinary importance for the induction of kidney differentiation and maturation. For a long time it has been debated whether immaturity of renal function might have any clinical consequences. It now seems clear that at least one aspect of renal immaturity, namely the high urinary sodium excretion in preterm infants, which often results in negative sodium balance, should be paid more attention to because it might interfere with growth. Two recent review articles discuss this issue. The profound changes in fluid and electrolyte homeostasis that occur in the neonatal period, involves most tissues. This is exemplified with some recent exciting studies on the changes in ion transport that occur in the lung around birth.

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Renal immaturity is pronounced in very low-birth-weight infants with a gestational age < or = 30 weeks. We attempted to elucidate if conditions requiring mechanical ventilation, including patent ductus arteriosus, might further compromise renal function due to decreased renal perfusion. Forty infants studied between 4 and 28 days of age were divided into four groups: Control with no patent ductus or mechanical ventilation (n = 8); PDA+MV, with both patent ductus and mechanical ventilation (n = 17); PDA, with patent ductus (n = 6); MV, with mechanical ventilation (n = 9). The groups PDA+MV and MV had significantly lower creatinine clearances and significantly higher fractional sodium excretions than controls. Mean arterial pressure was significantly lower in all groups compared to controls and correlated significantly with creatinine clearance (r = 0.47, p < 0.02). In conclusion, low renal function in these infants is further compromised by a patent ductus arteriosus and/or the use of mechanical ventilation.

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The cutaneous microcirculation was investigated before and 2-4 h after haemodilution in 13 newborn infants with polycythaemia. Skin microvascular perfusion was related to the haematocrit and to the presence of rhythmical changes in blood flow, reflecting vasomotor activity. The microcirculation was studied with a laser Doppler fluxmeter in a superficial microvascular bed represented by the dorsal hand skin. In five subjects, it was possible to combine laser Doppler flux measurements with microscopic quantitations of blood cell velocity in single, nailfold capillaries. In neonates less than 12 h postnatal age (n = 6), microvascular perfusion was only one-third that of the equally polycythaemic, but older infants (n = 7, p < 0.01). The higher perfusion in the older neonates with polycythaemia was associated with rhythmical variations in blood flow (3-5 cycles/min). There was no difference in skin temperature, blood pressure or heart rate between the two age groups. After haemodilution, the younger infants had developed rhythmical blood flow variations with the same characteristics as in the older group, in which the flow pattern was unchanged. In association, the laser Doppler flux had increased 304% in the younger and 73% in the older group (median values, p < 0.05 versus pretreatment values). The post-treatment change in laser Doppler flux corresponded to an increase in nailfold capillary blood cell velocity from 0.08 (0.02-0.23) mm/s prior to haemodilution to 0.21 (0.07-0.32) mm/s after treatment (n = 5, p < 0.05). Skin microcirculatory effects of neonatal polycythaemia and haemodilution vary in relation to vasomotor activity.

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In order to identify children with fatal outcome in a neonatal intensive care unit in which only outborns are admitted, a retrospective study over a 10-year period was undertaken. The study was limited to respiratory disorders. The aim of the study was to identify lethal risk factors and thereby the need for improving therapeutic tools. Diagnoses, perinatal history, ventilator settings, blood gases, medical treatment, X-ray findings, head ultrasounds, echocardiograms, laboratory tests, surgical procedures and autopsy findings were evaluated. Severe respiratory insufficiency requiring mechanical ventilation was found in 777 patients and of these babies, 207 (27%) died while still on the ventilator. Fifty-eight patients were excluded for various reasons and thus 149 patients were included in the study. It is concluded that the mortality rate from respiratory insufficiency in the material studied was consistently high over the 10-year period. New therapeutic modalities, one of which is ECMO, are offered nowadays in clinical practice and may improve mortality and morbidity rates.

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Development of glomerular and tubular renal function is delayed in preterm infants. To study the pattern of maturation during infancy and childhood, we re-evaluated renal function in 22 very low birth weight infants--in 14 of the infants at 18 months postconceptional age (9 months corrected age) and in the remaining 8 infants at 8 years of age. The glomerular filtration rate remained lower at 9 months corrected age than in term infants of the same postconceptional age: 82 +/- 23 versus 125 +/- 18 ml/min per 1.73 m2 (p < 0.001). At 8 years of age the glomerular filtration rate did not differ from that of healthy control subjects. Effective renal plasma flow, filtration fraction, albumin excretion, maximal concentrating ability, and kidney size determined by ultrasonography were all normal at 8 years of age. We conclude that renal function, which is markedly reduced during the neonatal period in very low birth weight infants, reaches normal maturity by 8 years of age but not by 9 months corrected age.

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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.

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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.

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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.

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A case of septicemia in a 7-day-old infant with a gentamicin-resistant strain of Klebsiella oxytoca prompted an epidemiological survey in a neonatal unit. Within a 3-month period 7 patients presented with symptomatic infection with gentamicin-resistant gram-negative bacilli. Another 3 patients were asymptomatic and only harboured the organisms in the stool. The aminoglycoside modifying enzyme ANT(2")-a was identified with a probe technique in different gram-negative species indicating the spread of a plasmid. After the replacement of gentamicin with amikacin and the adherence to proper barrier precautions the gentamicin-resistant strains disappeared from the ward.

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