Alcoholic ketoacidosis with multiple complications: a case report.

Alcoholic ketoacidosis is a poorly diagnosed medical emergency usually identified in chronic alcohol misusers following an abrupt cessation or reduction of alcohol consumption. A high index of suspicion should be maintained by acute physicians as response to treatment is rapid with complete resolution of metabolic derangements. Complications are usually the result of not instituting the correct treatment or not addressing associated conditions. We describe a case of alcoholic ketoacidosis with multiple complications at presentation.

The lens in hereditary hyperferritinaemia cataract syndrome contains crystalline deposits of L-ferritin.

BACKGROUND/AIM: Hereditary hyperferritinaemia cataract syndrome (HHCS) is an autosomal dominant disorder characterised by elevated serum L-ferritin and bilateral cataracts. The ocular manifestations of this disorder are poorly studied. This study therefore sought to determine the origin of cataracts in HHCS. METHODS: L-ferritin ELISA, immunohistochemical and ultrastructural analysis of a lens nucleus from an HHCS individual. RESULTS: The HHCS lens L-ferritin content was 147 microg/g dry weight of lens compared with <16 microg/g for a non-HHCS control cataract lens. The cataract comprised discrete crystalline inclusions with positive staining with anti-L-ferritin but not anti-H-ferritin. CONCLUSIONS: This unusual finding of crystalline opacities in the lens may be unique to HHCS and is likely to result from disturbed metabolism of L-ferritin within the lens or an abnormal interaction between L-ferritin and lens proteins.

Antenatal glucocorticoids modulate the amplitude of pulsatile cortisol secretion in premature neonates.

We hypothesized that antenatal exposure to glucocorticoids influences subsequent pulsatile cortisol (F) secretion in premature neonates. To test this hypothesis, blood was sampled for plasma F determination via indwelling arterial lines at 15-min intervals for 6 h in 26 clinically stable neonates whose gestational ages were 25-33 wk. Deconvolution analysis was used to characterize F secretion and elimination. Pulsatile F secretion was observed in all neonates. Deconvolution estimates in eight neonates exposed to antenatal glucocorticoids (ANG group) were compared with those of 18 neonates not or only remotely exposed to ANG (No/RG group). The median amplitude of the F secretory burst of the ANG group was significantly less than that of the No/RG group [4.3 nmol/Lv x min and 9.2 nmol/Lv x min, respectively; p = 0.026 (Lv is liter of F distribution volume)]. The number and duration of F secretory bursts was similar for both groups: 5 bursts per 6 h, and 23 versus 16 min. By univariate linear regression analysis, mean arterial blood pressure correlated positively with F secretory burst frequency and F production rate (p = 0.0035, r = 0.55 and p = 0.0067, r = 0.52, respectively). We propose that ANG treatment modulates the amplitude of pulsatile F secretion in premature neonates.

Ocular sequelae in extremely premature infants at 5 years of age.

OBJECTIVE: To report long-term ophthalmological sequelae in extremely premature infants at 5 years and to determine the relationship between neonatal variables (including retinopathy of prematurity; ROP) and the 5 year ophthalmological outcome of these infants. METHODOLOGY: The study cohort comprised 84 surviving infants born with a birthweight < 1000 g or gestational age < 28 weeks from June 1985 to December 1989. All infants had an ophthalmological assessment between 34 and 40 weeks post conceptional age to document grade of ROP and were assessed at 5 years of age for fundoscopy, visual acuity, refractive error and ocular mobility. RESULTS: Of the 84 long-term survivors 69 (82%) were formally assessed at 5 years. Overall, 30 (43%) had some form of ocular disorder. Nineteen (27%) had reduced visual acuity of < 6/6 and three of these were blind. Myopia > -0.5 dioptre was noted in eight (12%), hypermetropia > or = 2.0 dioptre in five (8%), astigmatism in seven (11%) and strabismus was present in nine (14%) of the cohort. There was a significant relationship (P < 0.0001) between the incidence of ocular disorders and ROP. However, even those premature children without ROP had a 31% incidence of ocular disorder at 5 years. CONCLUSION: Long-term ophthalmological follow-up is recommended in all extremely premature infants regardless of the presence of ROP in the neonatal period.

Helicobacter pylori infection and upper gastrointestinal patholgy in a British immigrant Indian community.

OBJECTIVES: To assess the pattern of upper gastrointestinal pathology and the prevalence of Helicobacter pylori infection in the Southall Indian community. DESIGN: A prospective study of endoscopic findings in 124 Indian and 107 whites from the Southall area. In a separate study blood samples were taken from 100 Indian subjects presenting to a single general practitioner in Southall. METHODS: The presence of gastritis and H. pylori infection was assessed histologically in Indian and white patients undergoing endoscopy. Serum samples were analysed using a specific enzyme-linked immunosorbent assay (ELISA) for anti-H. pylori immunoglobulin G. RESULTS: In the endoscopic study, Indian and white patients had the same rate of H. pylori infection (52% vs. 43%, respectively) (P= NS). The pattern of upper gastrointestinal pathology was similar in whites and Indians. In the general practice based study 41 subjects were H. pylori seropositive. Seropositivity increased with age (P<0.05). CONCLUSION: There is no excess of H. pylori-related pathology in Southall immigrant Indians. The similarity of upper gastrointestinal pathology in UK Indian and white patients presenting for endoscopy suggests that the high rates of duodenal ulceration, gastritis and H. pylori infection in India are environmentally rather than racially determined.

Hyperferritinaemia in the absence of iron overload.

BACKGROUND: Serum ferritin is normally a marker of iron overload. Ferritin genes are sited at chromosomes 19 and 11. Regulation of ferritin synthesis involves an interaction between an iron regulatory protein (IRP) and part of the ferritin mRNA designated the iron regulatory element (IRE). A disorder of ferritin synthesis resulting in hyperferritinaemia in the absence of iron overload has been described recently. PATIENTS AND METHODS: Hyperferritinaemia in the absence of iron overload was detected in a patient who was investigated for possible haemochromatosis. Serum iron, transferrin saturation, and ferritin concentration were studied in 11 members of this patient's family from three generations. Eight members had DNA samples analysed by direct cycle sequencing of the 5' untranslated region of the L ferritin gene. RESULTS: Six of the family members studied had serum ferritin concentrations greater than 900 micrograms/l. However, serum iron and transferrin saturation were normal in these subjects who all had evidence of cataracts. Three affected family members who had genetic studies of the L ferritin gene on chromosome 19 had an A to G point mutation which was not found in unaffected members. CONCLUSIONS: There was complete concordance between a mutated IRE, cataracts, and hyperferritinaemia in three generations of this family. This family study confirms the finding that hereditary hyperferritinaemia in the absence of iron overload is an autosomal dominant inherited disorder.

Survey of the definition and screening of neonatal hypoglycaemia in Australia.

OBJECTIVE: To determine the approach to identifying neonatal hypoglycaemia and the definition of neonatal hypoglycaemia used by neonatal paediatricians in Australian Level 3 neonatal intensive care units (NICU). METHODOLOGY: A questionnaire was sent to the 101 neonatal paediatricians in the 22 Level 3 NICU in Australia asking their method of screening for, and definition of, neonatal hypoglycaemia. RESULTS: Responses were received from 70 neonatal paediatricians, including all 22 directors. A bedside glucose meter is used in 19 of 22 NICU to screen for hypoglycaemia, whilst one NICU uses a glucose analyzer and another NICU uses a visual colour comparison method. One NICU does not screen, but has blood glucose measured in a satellite laboratory. If the screening method suggests hypoglycaemia, 62 of 63 neonatal paediatricians proceed to blood glucose determination in a laboratory, mostly using plasma samples. Based on the laboratory measurement, the definition of neonatal hypoglycaemia ranged from < 1.1 to 3.0 mmol/L. CONCLUSIONS: The majority of neonatal paediatricians in Australian NICU screen for neonatal hypoglycaemia using a bedside glucose meter. There is a wide range in the definition of neonatal hypoglycaemia from < 1.1 to 3.0 mmol/L.

Disposition, metabolism, and toxicity of methyl tertiary butyl ether, an oxygenate for reformulated gasoline.

Studies of the toxicology of methyl tertiary butyl ether (MTBE) were reviewed as a possible information base for evaluating the health effects of evaporative emissions from reformulated gasoline (RFG). The major metabolites of the oxidative demethylation of MTBE in vivo were methanol and tertiary butyl alcohol (TBA), whereas formaldehyde and TBA were the principal products of hepatic microsomal oxidation by cytochrome P-450. Pharmacokinetic studies in rats treated with intragastric MTBE in corn oil gave an initial disposition T1/2 for MTBE of 0.32 h. The decline in the serum drug versus time curve for MTBE in rats was accompanied by a progressive increase in serum methanol concentrations to levels more than 50-200 times those of the parent compound. Repeated exposure of MTBE vapor by inhalation in rats resulted in dose-dependent increases in MTBE in the blood, brain, and adipose tissue compartments. Blood concentrations of TBA were also dose dependent and provided an estimate of the total amount of MTBE distributed to peripheral drug metabolizing compartments. Perirenal fat/blood MTBE concentration ratios ranged from 9.7 to 11.6 after 15 wk of intermittent exposure. During an oxyfuels program in Fairbanks, AK, blood levels of occupationally exposed workers were 0.2-31.5 microgram/L MTBE and 1.6 to 72.2 microgram/L TBA with a mean TBA:MTBE blood concentration ratio of 4.2. In patients who received MTBE by percutaneous, transhepatic puncture for the dissolution of cholesterol gallstones, concentrations of MTBE in fat tissue reached 60 and 300 microgram/g at a treatment time when mean blood MTBE was less than 20 microgram/ml. The results of laboratory and clinical studies indicate that metabolites of MTBE may contribute to the nephropathy, neoplasms, and other pathological changes associated with repeated exposure to MTBE in experimental animals. It is concluded that such studies can provide a well-defined database for quantitative safety comparisons and health risk-benefit analyses of MTBE and other oxygenates in RFG.

The Neonatal Neurobiologic Risk Score: does it predict outcome in very premature infants?

OBJECTIVE: To examine the validity of the Neonatal Neurobiologic Risk Score (NBRS) for predicting neurodevelopmental outcome to 3 years in infants born at < 28 weeks gestation. METHOLDOLOGY: The NBRS was retrospectively determined for 56 consecutive infants cared for in our NICU and prospectively followed to 3 years. Neurodevelopmental assessments performed at 3 years were correlated with the NBRS, and the predictive powers of individual items in the NBRS determined. RESULTS: The mean (range) birth weight was 908 (514-1295) g and gestational age was 26 (24-27) weeks. Three-year outcome was abnormal in 12 (21%) infants. A high NBRS at discharge was associated with an increased risk of abnormal 3-year outcome (odds ratio 2.56; 95% C.I. 1.4-4.7, p = 0.002). A modified NBRS using only significantly predictive items (acidosis, hypoxemia, hypotension, intraventricular hemorrhage, infection and hypoglycemia) demonstrated high sensitivity (1.00), specificity (0.98), positive predictive value (0.92) and negative predictive value (1.00) for abnormal 3-year outcome. CONCLUSIONS: This study confirms the validity of the NBRS as a simple and objective means of identifying very premature infants at highest risk of abnormal neurodevelopmental outcome, and of identifying specific events which may contribute to such outcomes.

Predictive value of the Griffiths assessment in extremely low birthweight infants.

OBJECTIVE: To assess the relationship between the Griffiths Mental Development Scales at 1 and 3 years and the Stanford-Binet Intelligence Scale (S-B) and Beery Test of Visual-Motor Integration (VMI) at 5 years in extremely low birthweight (ELBW) children. METHODOLOGY: Prospective study of 45 ELBW infants, without severe neurosensory impairment, cared for in a single Level III neonatal intensive care unit. RESULTS: At 5 years, 36 (80%) children were of average intelligence, 8 (18%) had borderline intelligence and one was mentally retarded. The Griffiths general quotient (GQ) at 1 year had a weak correlation with the 5 year IQ (corr. coeff. = 0.47), with only 17% of children with a GQ < -1 s.d. at 1 year receiving an IQ < -1 s.d. at 5 years. In contrast, the Griffiths GQ at 3 years correlated strongly with 5 year IQ (corr. coeff. = 0.78). Among those children with a 3 year GQ < -1 s.d., 67% had a 5 year IQ < -1 s.d. and all had a 5 year 1Q < 89. The 3 year hearing and speech subscale correlated strongly with the 5 year S-B verbal comprehension factor (corr. coeff. = 0.753) and the 3 year combined eye/hand co-ordination/performance quotient had a moderate correlation with the S-B non-verbal reasoning factor (corr. coeff. = 0.597) and with the Beery VMI (corr. coeff. = 0.49). CONCLUSIONS: The 3 year Griffiths GQ is a good predictor of 5 year S-B IQ in ELBW children and can be used to identify children who may benefit from intervention prior to school entry.

Neonatal outcome in a randomized, controlled trial of low-dose aspirin in high-risk pregnancies.

OBJECTIVE: To determine the value of low-dose aspirin in high-risk pregnancies, and assess its impact on fetal growth, as well as on perinatal mortality and morbidity. METHODOLOGY: One hundred and eight women with singleton pregnancies were enrolled in a randomized, double-blind, placebo-controlled trial of 100 mg/day aspirin from 17 to 19 week gestation. Enrolment criteria included pre-existing chronic essential hypertension or renal disease, or a history of previous early, severe pre-eclampsia. RESULTS: There were four stillbirths (all aspirin) and two neonatal deaths (both placebo), to yield respective perinatal mortality rates of 69/1000 and 40/1000 (P = 0.499). Liveborn infants in the aspirin group were significantly more mature (P = 0.017) and of heavier birthweight (P = 0.034) but had similar length (P = 0.091) and head circumference (P = 0.257). Fewer infants in the aspirin group were liveborn prematurely (5/54 vs 14/50; P = 0.016) or were of low birthweight (3/54 vs 9/50; P = 0.052). There were no significant between-group differences for standard deviation (Z) scores for weight, length or head circumference, or for skinfold thickness measurements. There was no significant difference in occurrence of low Apgar scores or in neonatal intensive care unit use between the groups. CONCLUSIONS: Low-dose aspirin does not appear to have a significant effect on perinatal morbidity. The increase in weight at birth associated with low-dose aspirin therapy is due to prolongation of pregnancy rather than prevention of intra-uterine growth retardation.

Risk factors for sensorineural hearing loss in extremely premature infants.

OBJECTIVE: To identify potentially preventable risk factors for sensorineural hearing loss (SNHL) in extremely premature infants. METHODOLOGY: A case control study of survivors with gestational age (GA) < 28 weeks or birthweight (BW) < 1000 g using data collected prospectively in our Neonatal Intensive Care Unit database. Each subject with bilateral SNHL > 40 dB was matched according to GA, BW and sex with two controls who had neither sensorineural nor conductive hearing loss. RESULTS: Infants with SNHL had increased mean (+/- s.d.) days ventilated (53 +/- 21 vs 37 +/- 23 days, P = 0.006) and in oxygen (107 +/- 44 vs 69 +/- 28 days, P = 0.02) compared with controls. The risk for SNHL was increased for infants who spent > 90 days in oxygen (OR 4.0 [95% CI 1.1-15.6]), had maximum FiO2 > 0.90 (5.6 [1.2-26.9]), minimum plasma Na < 125 mmol/L (5.6 [1.1-27.8] or maximum pH > 7.60 (5.6 [1.1-89.0]). Neither maximum serum bilirubin nor exposure to ototoxic drugs was associated with SNHL. CONCLUSIONS: Avoidance of severe hyponatraemia and extreme alkalosis, as well as use of surfactant to minimize the severity of hyaline membrane disease, may result in a decreased incidence of SNHL in extremely premature infants.

Vitamin A status in preterm neonates with and without chronic lung disease.

It has been proposed that there is an association between vitamin A (VA) deficiency and the development of chronic lung disease (CLD) in preterm infants. This study was designed to measure the VA status in preterm infants and to compare the results in the group of babies who developed CLD with the group who did not. Vitamin A status was assessed by measuring plasma VA, retinol binding protein (RBP) and the plasma VA:RBP molar ratio in 25 infants of less than 31 weeks gestation during the first 28 days of life. Eleven babies developed CLD and 14 did not. There was no significant difference in plasma VA levels between the CLD and non CLD groups during the first 28 days. The majority of infants had adequate VA status, with a subgroup being deficient.

Extremely low birthweight infants at 3 years: a developmental profile.

This study documents the neurodevelopmental outcome at 3 years of 52 of 55 extremely low birthweight (ELBW) survivors (survival rate 49%) born in a tertiary maternity centre from July 1985 through December 1988, and examines more closely the developmental profile of the neurologically normal survivors. At 3 years, 6 (12%) children had severe neurodevelopmental impairment (severe cerebral palsy, blindness, deafness or a General Quotient (GQ) < 70 on the Griffiths Scales), 11 (21%) had mild to moderate impairment and 35 (67%) had no neurosensory impairment and normal development (GQ > or = 85). Significant risk factors for severe impairment were stage 3 or 4 retinopathy of prematurity (odds ratio [OR] 21.5), treatment with postnatal steroids (OR 21), grade III or IV intraventricular haemorrhage (OR 11) and supplemental oxygen at 'term' (OR 6.4). The developmental profile of the 35 neurologically normal children revealed a significant weakness in eye and hand coordination skills and a relative strength in hearing and speech skills. Early recognition of this developmental profile may allow implementation of more appropriate preschool programmes for ELBW children.

Longitudinal study of plasma ACTH and cortisol in very low birth weight infants in the first 8 weeks of life.

There are few published data on plasma ACTH and cortisol in very low birth weight (VLBW) infants beyond the first week of life. We therefore measured plasma ACTH and cortisol longitudinally in 25 infants (mean birth weight 1025 g, mean gestational age 28 weeks) at 1, 2, 4 and 8 postnatal weeks to document normative values for infants not receiving dexamethasone. We also examined the influence of clinical state and dexamethasone treatment on plasma ACTH and cortisol levels. Median plasma ACTH increased significantly with advancing postnatal age from 1 week to 8 weeks (21.0 vs. 40.0 ng/l; P = 0.01) but did not correlate with postconceptional age. Median plasma cortisol decreased significantly with advancing postnatal age from 1 week to 8 weeks (216 vs. 50 nmol/l; P = 0.001) and correlated inversely with postconceptional age (P = 0.004). At 8 weeks infants who were clinically well (n = 6) had lower plasma ACTH values compared with sick (n = 6) infants (median: 37.0 vs. 63.5 ng/l; P = 0.033). Plasma ACTH did not correlate with clinical state at 1, 2 and 4 weeks. At none of the postnatal ages studied was plasma cortisol influenced by the degree of sickness. Five infants received dexamethasone to assist weaning from mechanical ventilation. Their median plasma ACTH level, at 8 weeks, was significantly lower than that of the 12 infants who did not receive dexamethasone (11.0 vs. 40.0 ng/l; P = 0.0006). Plasma cortisol was not significantly influenced by dexamethasone treatment (P = 0.27). These data provide further information on the evolution of adrenocortical function in VLBW infants in the first months of life.

In-vitro fertilisation and neonatal ventilator use in a tertiary perinatal centre.

OBJECTIVE: To determine the contribution of livebirths resulting from in-vitro fertilisation and related technologies (IVF) to the use of neonatal ventilator beds. DESIGN: A retrospective review of records of all livebirths from our hospital's IVF program and all IVF infants receiving mechanical ventilation in our neonatal intensive care unit for the period 1985-1989. We also reviewed records of labour ward deliveries, neonatal intensive care unit admissions and transfer requests in order to obtain comparative data for livebirths of non-IVF infants whose mothers had been booked to deliver in our hospital. SETTING: A tertiary perinatal centre with a large IVF program and a Level 3 neonatal intensive care unit. RESULTS: IVF livebirths accounted for 5.1% of total ventilator bed days. Compared with non-IVF booked livebirths, IVF babies were more likely to require ventilation (odds ratio, 7.41; P less than 0.0001) and used more ventilator bed days per 100 livebirths (rate ratio, 9.63; P less than 0.0001), largely due to preterm delivery of multiple pregnancies; 42.3% of IVF babies who required ventilation were from triplet births and 38.5% from twin births. Nevertheless, even IVF singletons used more ventilator bed days per 100 livebirths than non-IVF booked livebirths (rate ratio, 2.78; P less than 0.0001). IVF livebirths accounted for 9.9% of the 78% increase in ventilator bed days used in 1989 compared with 1985. CONCLUSIONS: IVF livebirths accounted for only a small percentage of the overall use of neonatal ventilator beds, but consumed relatively more of such resources per livebirth than did non-IVF livebirths. The degree of risk of requiring ventilation is directly related to the number of infants in a multiple pregnancy, but even IVF singletons are at a relatively high risk of requiring ventilation.

Glycosylated haemoglobin in the diagnosis of diabetes mellitus in elderly people.

An oral glucose tolerance test (OGTT, 75 g WHO criteria) was applied to healthy elderly subjects (mean age 76 years) within a week of measurement of random blood glucose and glycosylated haemoglobin (HbA1). The 'Corning' method was used to assay HbA1 (established normal range for our laboratory 5-8%). Sixty-five subjects (38 women) of whom 54 were not diabetic on WHO criteria for OGTT participated in the study. Five of the 54 patients with non-diabetic OGTT results had abnormal HbA1 (greater than 8%). These five subjects had no evidence of impaired glucose tolerance. Eleven subjects had diabetic OGTT results of whom only four had raised HbA1 assay results. Seven subjects had normal HbA1 in spite of diabetic OGTT. The mean HbA1 in the group of subjects with normal OGTT (n = 52) was 6.7% (SD 1.05, range 4.6-8.7%). It appears from our study that the normal range of HbA1 in elderly subjects is not markedly different from established normal values. The poor sensitivity (36%) and predictive value (44%) of abnormal HbA1 in detecting diabetes, as shown in our study, would not permit its use for screening purposes nor as a confirmatory test for diabetes in elderly subjects.

Hyaline membrane disease and early neonatal aldosterone metabolism in infants of less than 33 weeks gestation.

We studied urine excretion of free and conjugated aldosterone by 12 control infants and 14 infants with hyaline membrane disease (HMD) on the first and seventh days after birth. Both groups had a mean gestational age of 29 weeks. Total urine aldosterone excretion (UAE) and percent excreted as conjugate were similar for both groups on both study days, and did not relate to the severity of respiratory failure in infants with HMD. Sodium intake was higher for infants with HMD on both study days (p less than 0.02), but their urine sodium excretion was only significantly (p less than 0.01) higher on day 7. For total UAE values greater than 3 nmol/kg/d, there was no significant difference between estimated sodium-potassium exchange by control (22 +/- 5%, n = 8) and HMD (31 +/- 5%, n = 10) groups. These data suggest that neither the magnitude of excretion of aldosterone in the urine, the ability to conjugate aldosterone nor the degree of relative distal tubular unresponsiveness to aldosterone are related to the severity of pulmonary immaturity in preterm infants.