Heart murmurs recorded by a sensor based electronic stethoscope and e-mailed for remote assessment.

BACKGROUND: Heart murmurs are common in children, and they are often referred to a specialist for examination. A clinically innocent murmur does not need further investigation. The referral area of the University Hospital is large and sparsely populated. A new service for remote auscultation (telemedicine) of heart murmurs in children was established where heart sounds and short texts were sent as an attachment to e-mails. AIM: To assess the clinical quality of this method. METHODS: Heart sounds from 47 patients with no murmur (n = 7), with innocent murmurs (n = 20), or with pathological murmurs (n = 20) were recorded using a sensor based stethoscope and e-mailed to a remote computer. The sounds were repeated, giving 100 cases that were randomly distributed on a compact disc. Four cardiologists assessed and categorised the cases as having "no murmur", "innocent murmur", or "pathological murmur", recorded the assessment time per case, their degree of certainty, and whether they recommended referral. RESULTS: On average, 2.1 minutes were spent on each case. The mean sensitivity and specificity were 89.7% and 98.2% respectively, and the inter-observer and intra-observer variabilities were low (kappa 0.81 and 0.87), respectively. A total of 93.4% of cases with a pathological murmur and 12.6% of cases with an innocent murmur were recommended for referral. CONCLUSION: Telemedical referral of patients with heart murmurs for remote assessment by a cardiologist is safe and saves time. Skilled auscultation is adequate to detect patients with innocent murmurs.

[Breast feeding in Tromsö before and after the baby-friendly-hospital initiative]. / Amming i Tromsø før og etter mor-barn-vennlig initiativ.

BACKGROUND: "The-Baby-Friendly Hospital Initiative" was introduced in the early 1990s by WHO/UNICEF to reverse a declining trend in breastfeeding worldwide. We wanted to investigate factors influencing breastfeeding and whether this initiative, introduced between 1993 and 1996, had improved breastfeeding in our region, Tromsø, a mid-sized city in northern Norway. MATERIAL AND METHODS: Medical records at maternal and child health centres of 1,374 infants born 1992 (n = 653) and 1997 (n = 721) were studied. The number of mothers breastfeeding, duration of lactation, parents' age, their occupation and education, maternal marital status and parity were registered. RESULTS: In a multiple regression analysis, birth, year 1997, high parental level of education/occupational prestige, and higher maternal age significantly prolonged the total period of breastfeeding. Parental age, education/occupation, the number of women starting breastfeeding, the duration of exclusive breastfeeding and the total lactation period significantly increased from 1992 to 1997. When correcting for parental age and education/occupation in a multiple regression analysis we found an increase in exclusive breastfeeding and the total lactation period by 0.5 month (mean (95% CI)) 0.5 (0.2-0.8) and 1.1 month (0.6-1.5) respectively. INTERPRETATION: This improvement might be due to "the Baby-Friendly Hospital Initiative", but also to unknown factors.

Antenatal, neonatal and post neonatal deaths evaluated by medical audit. A population-based study in northern Norway - 1976 to 1997.

BACKGROUND: Perinatal committees evaluate deaths by medical audit to improve antenatal and neonatal care. We report data from Troms County from 1976 to 1997. SUBJECTS AND METHODS: Antenatal, neonatal and post neonatal deaths (n=472) at > or = 20 weeks of gestation have been evaluated. Data were collected from the Medical Birth Registry of Norway and from medical records. Pregnancy risk factors, mortality rates, causes of deaths, non-optimal care and avoidable deaths were recorded. RESULTS: The death rate (all deaths per thousand total births) declined from 13.8 (1976-80) to 7.7 (1992-97), (p<0.001), due to a reduced death rate in preterms > or = 24 weeks (p<0.001) and in those between 500 and 1995 g (p<0.001). Antenatal deaths decreased (p<0.001) due to reduced intrapartum deaths (p<0.001). Prelabor deaths, unexpected intrauterine pre-hospitalization deaths included, did not change. Postnatal deaths declined (p=0.01) due to reduced early neonatal mortality (p=0.002). Deaths from malformations (p<0.001), fetal and neonatal infections (p=0.03) and placental disorders (p<0.001) declined. Non-optimal care (22.5% of deaths, 2.3%o of total births), avoidable deaths (13.1% of deaths, 1.3% of total births), and maternal neglect (7.5% of cases with non-optimal care, 0.6% of total births) did not change. Death during transport was rare (n=5), and no deaths occurred at maternity homes. Non-cohabitance, smoking and undiagnosed SGA new borns declined, and the level of education increased in the study population. CONCLUSION: The improvement is due to a reduction in intrapartum deaths and early neonatal mortality in preterms. A constant high rate of unexpected intrauterine deaths in non-hospitalized patients is a challenge for antenatal health care providers.

Neonatal alloimmune thrombocytopenia due to anti-HPA 1a antibodies; the level of maternal antibodies predicts the severity of thrombocytopenia in the newborn.

Eleven thousand one hundred pregnant women were genotyped for human platelet antigen HPA 1, and 198 HPA 1bb women were followed in the pregnancy with quantitative assay for anti-HPA la antibodies. Antibodies were detected in 24 women, and nine children were born with severe thrombocytopenia (< 50x10(9)/L). All mothers with high levels of antibodies were delivered of children with severe thrombocytopenia. None of the newborn infants had clinical signs of intra-cranial haemorrhage. The level of maternal anti-HPA 1a antibodies is predictive for fetal thrombocytopenia and may be used in decisions related to time and mode of delivery.

[Children with birth weight 1500 g or under from Troms and Finnmark in the period 1978-1989]. / Barn med fødselsvekt < or = 1,500 g fra Troms og Finnmark i perioden 1978-89.

During 1978-89, 245 women in Troms and Finnmark counties gave birth to 265 liveborn with birth weight < or = 1,500 g. The incidence of liveborn < or = 1,500 g, and of live- and stillborn < or = 1,500 g did not change significantly during the study period, but the stillborn proportion of live- and stillborn < or = 1,500 g decreased. The proportion of patients that had intrauterine transfer to hospitals with neonatal intensive care unit (72%), and neonatal transport (17%) did not change significantly. The mortality rate was constant (34%), probably due to change in registration practice leading to an increase in liveborn < or = 750 g. The handicap rate at four years of age decreased from 21% in 1978-81 to 12% in 1986-89, although the rates of moderate (8%) and severe (2%) handicap were unchanged. Cerebral palsy occurred in 10%, and blindness due to retinopathy of prematurity in 1%. The results are compatible with those of other studies from the same period.

Very low birthweight infants: outcome in a sub-Arctic population.

OBJECTIVE: To evaluate the outcome for very low birthweight (VLBW) infants in northern Norway. SUBJECTS AND METHODS: All live born infants (n = 536) with birthweight < or = 1500 g born during 1978-89 to women residing in the northern health region of Norway were studied retrospectively. Data were from the Medical Birth Registry (MBR), hospital records and from follow-up recordings to 4 y of age at maternal and child health centres. Stillborn infants (n = 269) with birthweight < or = 1500 g during the same period were also registered. RESULTS: The annual incidence of live born VLBW infants (7.1/1000 live births) did not change, but the proportion of infants born alive before 26 weeks' gestation increased and the stillborn part decreased significantly. The Caesarean section (CS) rate, antenatal transfer and the use of a neonatal transport team increased significantly. Four hundred and seventy-five infants (89%) were considered viable at birth, 347 (65%) survived to 1 y and 343 (64%) to 4 y. The likelihood of survival was independently related to female gender. The trend for survival to 4 y of age did not increase significantly. Thirty children suffered from cerebral palsy (8.7% of survivors, 5.6% of live births) and the cerebral palsy rate for infants with birthweight 751-1000 g decreased. The proportion of survivors considered to be normal or mild disabled increased and the part suffering from moderate or severe disability decreased significantly. CONCLUSIONS: In spite of long distances and unfavourable climatic conditions VLBW infants can be adequately cared for in this sparsely populated region of Norway.

The use of CRIB (clinical risk index for babies) score in auditing the performance of one neonatal intensive care unit.

The CRIB (clinical risk index of babies) score was developed to overcome the disadvantages of birthweight-specific comparisons between neonatal units. The aims of this study were to assess the ability of CRIB score compared to birthweight and gestational age to predict hospital mortality in very low birthweight infants and to use CRIB score in auditing one unit's performance during a prolonged time period. The charts of 335 infants with birthweight < or = 1500 g born between 1980 and 1995 were reviewed retrospectively. CRIB predicted hospital mortality significantly better than birthweight and gestation and performed equally well, whether the infants were treated with synthetic surfactant or not. When adjusting for CRIB score there was a significant improvement in the unit's performance, probably owing to the introduction of surfactant. As small samples tend to be associated with wide confidence intervals, use of CRIB is recommended in comparing risk adjusted mortality in a single unit over several years, as in this study, or between large groups of neonatal units over shorter periods.

Acute osteomyelitis in children: a population-based retrospective study 1965 to 1994.

OBJECTIVES: To investigate changes in occurrence, clinical features, laboratory and other investigations, aetiology and use of antibiotics, and to calculate the incidence of acute hematogenous osteomyelitis (AHO) in children up to 12 y of age in the county of Troms in the northern part of Norway. METHODS: Retrospective chart review of 86 children, newborn to 11 y old. with AHO between 1965 and 1994. RESULTS: A constant yearly incidence (95% CI) of 0.1 (0.08-0.12) per 1000 children could be calculated (X2 for trend 0.51;p = 0.48). The female proportion (95% CI) was 0.6 (0.48-0.72). The median duration of complaints prior to admission was 4 days. Erythrocyte sedimentation rate (ESR; mean (95% CI)= 59 mm/h (52-66)) and C-reactive protein concentration (CRP; mean (95% CI)= 63 mg/l (36-90)) were elevated in 96% and 89%, respectively. Local and/or blood cultures were taken in 97%. In 55% an agent was found. Staphylococcus aureus (S. aureus) was responsible in 76%. The proportion of betalactamase-producing strains tended to increase (49%; X2 for trend 3.72; p = 0.054). In 78% the long bones of the upper or lower extremities were affected. Penicillin or ampicillin combined with cloxacillin or dicloxacillin was the preferred therapy. The median duration of antibiotic treatment was 7 weeks. The use of penicillin declined (p = 0.008), whereas that of cloxacillin/dicloxacillin increased (p < 0.001). The use of ampicillin was unchanged (p = 0.79). CONCLUSION: The study confirms reports from various epochs and remote regions concerning the unchanged characteristics of AHO in children, except for the high proportion of females in the present study. An incidence for childhood AHO in a defined geographical region is given.

Role of endocardial endothelial cells in the turnover of hyaluronan in Atlantic cod (Gadus morhua).

The fate of the major connective tissue polysaccharide hyaluronan, as it appears after release from the matrix, was studied in the Atlantic cod by use of subcutaneous administration of hyaluronan conjugated with fluorescein isothiocyanate (FITC) and labelled with 125I. After administration, the ligand was transported to the heart, which contained 58% of the recovered label after 22 h, whereas 36% remained at the injection site. Uptake in other organs was low. Results from intravenous co-injection studies showed that 125I-FITC-hyaluronan and native hyaluronan were in competition for uptake by the same receptor in cod heart. Fluorescence microscopy revealed that FITC-hyaluronan accumulated in spherical structures and discrete vesicles in endocardial endothelial cells lining the muscular trabeculae of both heart chambers. Immunoelectron microscopy showed that, in these cells, the ligand lined the limiting membrane of endosomes and filled the lumen of late endosomes or lysosomes. We conclude that, in the cod, heart endothelial cells are essential for the turnover of hyaluronan. Atrial endothelial cells were also able to ingest 2-microm latex beads, although these were far more effectively phagocytosed by head kidney macrophages. The present results strengthen the notion that the cod endocardium consists of specialized scavenger endothelial cells, resembling sinusoidal endothelial cells of salmonid kidney and mammalian liver. These cells should therefore be regarded as an important part of the cod reticulo-endothelial system.

Hyaluronan injected in the anterior chamber of the eye is catabolized in the liver.

Catabolism of hyaluronan was studied by injecting hyaluronan (M(r) 200,000) labelled with [125I]-tyramine cellobiose, ([125I]-TC), into the anterior chamber of the rabbit eye. After endocytosis [125I]-TC accumulates in cells, allowing localization of the site of catabolism. When 0.1 ml of the aqueous humour was replaced with an equal volume containing polymer in tracer quantities, 24% was recovered from the eye at 2 hr and 6.5% at 6 hr after injection. With replacement of 0.2 ml of aqueous humour 38% and 19%, respectively, were found within the eye at the same time points. Most of the radioactivity was found in the liver. If the tracer was mixed with Healon the removal from the anterior chamber was delayed. Chromatography on Sephacryl S-300 showed that there was no significant degradation of the labelled polymer in the aqueous humour nor in the remaining parts of the enucleated eye, while most of the tracer extracted from the liver was of low molecular weight. Thus the labelled hyaluronan was being washed out of the eye and subsequently taken up and catabolized by the liver.

Coeliac disease and gluten-free diet: a following-up study of fifteen young adults.

Fifteen patients with coeliac disease diagnosed in infancy and early childhood between 1959 and 1971 were included in the study. The primary diagnosis was made on the basis of typical symptoms and signs, stool examination for fat, xylose test and clinical and laboratory improvement after introduction of gluten-free diet. All patients were challenged with gluten for a minimum of 4 weeks to 4 years before a peroral proximal jejunal biopsy was performed between 1973 and 1976. The biopsy specimen showed changes consistent with coeliac disease in all patients. Gluten-free diet induced again clinical recovery and was recommended as a life-long diet. The patients were reinvestigated after 15-18 years (mean 17 years) and 13 biopsies were evaluated. Five of these biopsy specimens showed variable histopathological changes. Only 5 patients were still on a strict gluten-free diet. There was no correlation between the presence of gastro-intestinal symptoms and abnormal biopsies. All patients had haematological tests within the normal range. Anti-gliadin IgA levels above the upper normal limit were found in 2 out of 3 patients with grade IV histopathological changes in the mucosa, and in 1 of the patients on a normal diet who refused to have a biopsy performed. The patients' knowledge of their disease was evaluated, and suitable follow-up programs for coeliac patients are discussed.

[Streptococci group B and pregnancy. Need for routine check-ups?]. / Gruppe B-streptokokker og graviditet. Behov for rutinemessig kontroll?

Group B streptococci are a major cause of perinatal infections and affect 1-5 infants out of every 1,000 live births. Maternal vaginal colonization with these bacteria is common (5-25%), and has been associated with late abortions, foetal growth retardation, early rupture of membranes and premature delivery. Colonization with group B streptococci may be observed in more than 70% of neonates born to mothers with the bacteria in their vaginal tracts at delivery. A high number of bacteria in the maternal urogenital tract during pregnancy may predispose to early-onset disease in neonates. The estimated attack rate in colonized neonates is 1-2%. A high specific IgG antibody concentration in the mother may protect the infant, but probably not before 32 weeks of gestation. Colonized women who are unable to produce such antibodies risk having affected offspring. Neonatal infection with group B streptococci frequently results in death or permanent neurologic morbidity; especially from the early-onset type (case-fatality more than 50%) which is most often vertical transmitted. Four cases with early-onset disease illustrate the severity of perinatal group B streptococcal infections. The severity and outcome of the disease may be moderated by screening for group B streptococci during late pregnancy. This screening must be combined with special attention to irregularities in pregnancy or perinatal complications.

Catabolism of hyaluronan in the knee joint of the rabbit.

Catabolism of hyaluronan was studied by injecting hyaluronan labelled with [125I]-tyramine cellobiose ([125I]-TC) into knee joints of rabbits. After endocytosis [125I]-TC remains intracellularly allowing localization of the site of catabolism. At 6 hours after injection 63% could be recovered in and around the joint, while at 48 hours 32% remained locally. Chromatography showed that 12% of the injected tracer was degraded in joint tissues at 6 hours, increasing to 33% at 24 hours. There was no apparent degradation within the joint fluid. No tracer was found in the regional lymph glands, but 16% of the injected tracer was detected in the liver at 24 hours. This investigation demonstrates that hyaluronan in the joint can be degraded both locally and in the liver.

Catabolism of hyaluronan in rabbit skin takes place locally, in lymph nodes and liver.

The catabolism of hyaluronan has been studied by injecting hyaluronan, labelled with 125I-tyramine cellobiose (125I-TC), subcutaneously into the hindpaw of rabbits. Following endocytosis, 125I-TC remains in the cells at the site of uptake, allowing localization of the site of catabolism. At 6 h after subcutaneous injection, 65% of the injected radioactivity was recovered. The skin at the injection site contained 47%, the popliteal gland at the side of injection 10%, and the liver 8% of the injected dose. At 48 h the three organs contained 40% of the injected dose with 17% in the skin, 10% in the lymph node and 13% in the liver. The decline in recovery could be accounted for by urinary excretion of the tracer, implying that some tracer had been released from the cells after endocytosis. Chromatography revealed that over 85% of 125I-TC-hyaluronan in the lymph nodes and liver was of low molecular mass throughout the experiment. In skin, 4% of the injected tracer was recovered with low molecular mass at 6 h, increasing to 12% of injected dose at 24 and 48 h. Thus, a minimum of 12% of the injected tracer was catabolized per 24 h at the skin injection site. If cells in skin are responsible for the subsequent release of tracer, as seen from the decrease in recovery of the injected dose, another 10-15% of the tracer could have been catabolized locally in the skin per day. The major part of the hyaluronan injected in the skin was, however, catabolized by lymphatic removal and subsequent degradation in local lymph nodes and liver.

Does VLDL-LDL-cholesterol in cord serum predict future level of lipoproteins?

Lipoproteins were measured in 618 healthy, full-term newborns. Seventy-four with a VLDL-LDL-cholesterol above 1.3 mmol/l (50 mg/dl) at birth and 25 randomly chosen controls with VLDL-LDL-cholesterol 1.3 mmol/l or below at birth were followed up at age 2. Seventy-two (52 in the high VLDL-LDL-cholesterol group and 20 in the low VLDL-LDL-cholesterol group) were followed up at age 13. At age 2 mean total cholesterol was 5.48 mmol/l (SEM 0.10) in the children with a high VLDL-LDL-cholesterol at birth, compared to 4.69 mmol/l (SEM 0.17) in the children with a low VLDL-LDL-cholesterol at birth (p less than 0.001). A difference was still present at age 13 (4.74 mmol/l; SEM 0.11 versus 4.20 mmol/l; SEM 0.14; p less than 0.01). At age 13 apolipoprotein B was 0.74 g/l (SEM 0.02) in the children with a high VLDL-LDL-cholesterol at birth, compared to 0.65 g/l (SEM 0.02) in the children with a low VLDL-LDL-cholesterol at birth (p less than 0.01). Children with high VLDL-LDL-cholesterol at birth might be more liable to high lipoprotein serum levels later in life.

Evaluation of fetal and neonatal mortality at the University Hospital of Tromsø, Norway, from 1976 to 1989.

To investigate developments in perinatal care, all fetal and neonatal deaths among those born after at least 24 weeks of gestation at the University Hospital of Tromsø, Norway from 1976 to 1989, were subjected to medical audit. A decrease in total mortality rate was found when based on maturity (greater than or equal to 24 weeks; 19.9-13.4%; p less than 0.01), and/or birth weight (greater than or equal to 500 g; 19.2-13.4%; p less than 0.05). This was mainly due to a decrease in fetal deaths (14.8-6.6%; p less than 0.0001). Deaths during labor (5.4-1.1%; p less than 0.001), and deaths before the onset of labour (9.4-5.5%; p less than 0.05) declined. The neonatal death rate remained virtually constant (5.2-6.8%). The incidence of conditions affecting the placenta and the umbilical cord, causing asphyxia and intra-uterine growth retardation, declined, from 9.2 to 5.0% (p less than 0.01), as did that caused by immaturity (2.8-1.3%; p less than 0.05). The rates of death caused by cerebral hemorrhage, respiratory distress syndrome, infections, and malformations did not change. There was no significant proportional change in the causes of death from the first to the last period. The rate of fetal death following suboptimal care declined (2.4-0.4%; p less than 0.01), while the corresponding neonatal death rate remained unchanged (0.9-1.1%). The proportions of both fetal and neonatal deaths occurring after suboptimal care were low (fetal: 16.2, 8.8, and 5.6%; neonatal: 17.1, 23.5, and 16.2%). These differences did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

The origin and fate of hyaluronan in amniotic fluid.

The mechanisms which regulate the steady-state concentration and molecular weight of hyaluronan in the amniotic fluid of sheep at different gestational ages have been investigated. An attempt to trace the origin of the polysaccharide has been made by analyses of various fetal fluids (amniotic fluid, allantoic fluid, tracheal fluid, urine, and serum). The fate has been studied by injection of radioactively labelled hyaluronan into the amniotic cavity and following the tracer in fetal tissues and fluids. The concentration of hyaluronan in amniotic fluid varies considerably but is in the order of 5 mg/l at mid-pregnancy and decreases to 1 mg/l in late pregnancy. The polysaccharide has a Mr-distribution with a weight-average in the order of 10(6) at 10 to 13 weeks of gestation which decreases to 10(5) closer to term. Calculations show that urine contributes 0.1 and 0.5 mg of low-molecular (Mr = 10(4) hyaluronan per day in mid- and late pregnancy, respectively, and the lung 10-20% of that amount in the form of high-molecular weight polymer (Mr greater than 10(6). The hyaluronan disappears from the amniotic cavity by bulk flow due to fetal swallowing. It is taken up and degraded in the fetal intestine. Molecules of Mr = 10(3) can pass the intestinal barrier. Calculations show that about 0.5 mg and 1.0 mg of hyaluronan is eliminated per day from the amniotic fluid at 12 and 17 weeks of gestation, respectively. Thus, the higher rate of elimination and the relatively high urinary contribution in more mature fetuses explain the low concentration and Mr of amniotic hyaluronan in late gestation, whereas a slower elimination combined with a relatively larger contribution of high molecular weight hyaluronan both from lung and urine and possibly from other sources are responsible for the higher concentration and Mr of the compound in early pregnancy.

Elimination and subsequent metabolism of circulating hyaluronic acid in the fetus.

Hyaluronic acid differs from other glycosaminoglycans in its lack of covalently linked peptide, absence of sulphate groups, and the exceptional size of its single-chain polymers. These differences can be related to its distinct physical and functional properties, and may be pertinent to its greater abundance in early tissue development. In mature animals, the turnover of hyaluronic acid in tissues is reflected at least partly in the blood stream. The metabolism of circulating hyaluronic acid was therefore studied in fetal sheep after intravenous injection of [3H]acetylhyaluronic acid. Between 95% and 99% was removed within 6 min. Plasma radioactivity decayed by first-order kinetics, with a half-life between 0.8 and 1.25 min. The rate of elimination did not vary materially with hyaluronic acid fractions of widely disparate average Mr or with fetal age between 70 and 120 days. 3H2O was detected in plasma within 8-10 min. Labelled material found in urine from 10 min onward included polymers greater than or equal to 70,000 Mr, which indicates that urine may be a source of hyaluronic acid in amniotic fluid. Elimination from the plasma took place mainly in the liver, where labelled material was largely recovered in small metabolic residues as early as 28 min after injection. These were shown by high pressure liquid chromatography (h.p.l.c.) to include water, acetate, N-acetylglucosamine and a fraction tentatively identified as N-acetylglucosamine 1-phosphate. Tritium radioactivity was detected in hepatic lipids but not those of the spleen. Estimated plasma turnover was in the order of 10 micrograms/min per kg body weight. This is about 3-10 times that in adult animals and is consistent with an increased inflow of hyaluronic acid generated during the maturation of developing tissues.

Preparation of biologically intact radioiodinated hyaluronan of high specific radioactivity: coupling of 125I-tyramine-cellobiose to amino groups after partial N-deacetylation.

Hyaluronan was substituted with tyramine-cellobiose on amino residues exposed after hydrazinolytic N-deacetylation of the polysaccharide. Nonsubstituted amino groups were reacetylated, and the carboxylic hydrazides were removed by treatment with HIO3. The adduct was labeled with 125I before or after coupling to hyaluronan. N-deacetylation increased with prolonged pretreatment with hydrazine, which also reduced the chain length of hyaluronan. Hydrazinolysis for 30 min produced hyaluronan with Mr 2.2-2.9 x 10(5). This material was substituted with varying amounts of tyramine-cellobiose (from 1 per 20 to 1 per 130 disaccharides). Hyaluronan labeled in this way was recognized by Streptomyces hyaluronidase, hyaluronan affinity protein of cartilage proteoglycan, and receptors for specific endocytosis of hyaluronan in liver endothelial cells. Since tyramine-cellobiose is nondegradable and therefore is arrested intralysosomally at the site of uptake, turnover studies of hyaluronan can be easily carried out with this ligand.