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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 253 records · Page 14Linked to original sources

Safe feeding practices for infants and young children.

OBJECTIVE: To review local and overseas experience of food asphyxia in children and to examine aspects of safe childhood eating practices. METHODOLOGY: Inpatient separation information data for childhood hospital admissions in South Australia were searched for episodes of food-induced airway obstruction and case records of the Department of Histopathology at the Women's and Children's Hospital were searched for cases of fatal food asphxia. RESULTS: While other forms of injury to young children appear to be declining in numbers, episodes caused by choking on food have remained relatively constant. The increase in average length of hospital stay (from 2.8 days in 1989-90 to 5.2 days in 1993-94) also suggests that the episodes have been more severe. Two fatal cases were also found. CONCLUSIONS: Choking due to food inhalation is a problem with potentially fatal consequences. Young children are particularly at risk as they have immature dentition and control of swallowing, and lack experience of food. Although young children should avoid potentially dangerous foods such as raw carrot sticks and raw apples, certain currently available information packages for parents recommend these foods.

Airway Obstruction↗

Altered lipopolysaccharide characteristic of the I69 phenotype in Haemophilus influenzae results from mutations in a novel gene, isn.

The 169 phenotype of Haemophilus influenzae results from a mutation leading to a lipopolysaccharide molecule consisting only of lipid A and a single phosphorylated 2-keto-3-deoxyoctulosonic acid residue. In this paper we describe the identification of a gene which, when mutated, results in the 169 phenotype. We have named the gene isn. The predicted amino acid sequence of Isn is homologous to the product of the lmbN gene involved in the biosynthesis of the sugar-containing antibiotic lincomycin by Streptomyces lincolnensis. lsn is situated between two loci that are homologous to the dpp and art periplasmic permease systems in Escherichia coli. Northern (RNA) blot and primer extension analyses reveal that isn is transcribed as a monocistronic mRNA. Potential functions of Isn protein are discussed.

Amino Acid Sequence↗

Ultrasound findings and clinical antecedents of cerebral palsy in very preterm infants.

OBJECTIVE: To investigate the incidence and timing of neonatal ultrasound lesions, and clinical details about pregnancy and the perinatal period, in a total population of extremely premature children with cerebral palsy, born to mothers who were resident in Oxfordshire. METHODS: Eighteen children born at less than 32 completed weeks of gestation were identified from a regional cerebral palsy register. Eighteen controls were matched for gestation, time, and place of birth. Perinatal records and ultrasound reports were systematically reviewed. Sequential neonatal ultrasound images stored on videotape were reanalysed, blind to the outcome of the infants. RESULTS: Sixteen (89%) of the cerebral palsy cases and one (6%) control had parenchymal cysts on neonatal brain scans. Of the cerebral palsy cases, none had cysts detectable on the first day. Six developed cysts within the first 10 days of life, and two of these had periventricular echodensities when first scanned postnatally. Antenatal complications were recorded in 16 cases and nine controls. The early postnatal appearance of cysts in a few babies with a history of severe antenatal complications suggested that antenatal factors may have contributed to the cerebral pathology. CONCLUSIONS: Intrauterine factors may have contributed to adverse neurological outcome, but 16/18 of the preterm cerebral palsy cases had an associated cerebral lesion which developed in the perinatal period.

Brain Diseases↗

Clinical associations and time of onset of cerebral white matter damage in very preterm babies.

Neuropathological examinations were carried out at necropsy on 83 very pre-term babies who died during their first hospital admission. Forty seven (57%) babies had evidence of cerebral damage-39 with ischaemic white matter damage. The time of onset of ischaemic lesions was thought to be prenatal in 12 cases (31%) and postnatal in a further 12 (31%). The exact timing of damage could not be determined in 15 (38%) cases. Maternal and neonatal case notes were reviewed to ascertain clinical associations of ischaemic white matter damage. There were no clear associations between adverse clinical factors and prenatal ischaemic white matter damage. In contrast, pre-eclampsia, intrauterine growth retardation, and delivery without labour were associated with postnatal damage as were neonatal sepsis, necrotising enterocolitis, and seizures. The absence of a clear association between the timing of adverse clinical factors and the timing of ischaemic cerebral damage suggests that cerebral damage in very preterm babies may result from a sequence of events rather than one specific insult.

Brain↗

Analysis of parent of origin specific DNA methylation at SNRPN and PW71 in tissues: implication for prenatal diagnosis.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct developmental disorders caused by absence of paternal or maternal contributions of the chromosome region 15q11-q13, resulting from deletions, uniparental disomy (UPD), or rare imprinting mutations. Molecular cytogenetic diagnosis is currently performed using a combination of fluorescence in situ hybridisation (FISH), DNA polymorphism analysis, and DNA methylation analysis. Only methylation analysis will detect all three categories of PWS abnormalities, but its reliability in tissues other than peripheral blood has not been examined extensively. Therefore, we examined the methylation status at the CpG island of the small nuclear ribonucleoprotein associated polypeptide N (SNRPN) gene and at the PW71 locus using normal and abnormal lymphoblast (LB) cell lines (n = 48), amniotic fluid (AF) cell cultures (n = 25), cultured chorionic villus samples (CVS, n = 17), and fetal tissues (n = 18) by Southern blot analysis with methylation sensitive enzymes. Of these samples, 20 LB cell lines, three AF cultures, one CVS, and 15 fetal tissues had been previously diagnosed as having deletions or UPD by other molecular methods. Methylation status at SNRPN showed consistent results when compared with FISH or DNA polymorphism analysis using all cell types tested. However, the methylation pattern for PW71 was inconsistent when compared with other tests and should therefore not be used on tissues other than peripheral blood. We conclude that SNRPN, but not PW71, methylation analysis may be useful for diagnosis of PWS/AS on LB cell lines, cultured amniotic fluid, or chorionic villus samples and will allow, for the first time, prenatal diagnosis for families known to carry imprinting centre defects.

Amniotic Fluid↗

Growth of acid fast L forms from the blood of patients with sarcoidosis.

BACKGROUND: Acid fast cell wall deficient forms (CWDF) of bacteria have been grown from blood, bronchial washings, and ocular anterior chamber fluid from patients with sarcoidosis. A monoclonal antibody raised against Mycobacterium tuberculosis whole cell antigen (H37RV) was used to characterise further CWDF grown from the blood of patients with sarcoidosis. METHODS: Blood from 20 patients with active sarcoidosis and from 20 controls was cultured using methods favourable for the growth of CWDF. Isolates were further characterised by indirect fluorescent antibody analysis using a monoclonal antibody highly reactive with M tuberculosis. RESULTS: CWDF were grown from the blood of 19 of 20 subjects with sarcoidosis. All isolates stained positively with the monoclonal antibody and with a modified Kinyoun stain. No organisms were grown from the blood of controls. CONCLUSIONS: These data demonstrate that CWDF can be grown from the blood of nearly all patients with active sarcoidosis. The results confirm that the organisms are mycobacterial in origin and are similar, if not identical, to M tuberculosis. Their role in the pathogenesis of sarcoidosis is unknown.

Fluorescent Antibody Technique, Indirect↗

Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake.

To better define the time course of skeletal muscle glucose uptake and its modulation by changes in perfusion, we performed systemic euglycemic-hyperinsulinemic clamps (40 mU.m-2.min-1) for a 90-min period in a group of lean, insulin-sensitive subjects (n = 9) on two occasions (approximately 4 wk apart) with insulin-mediated vasodilation intact or inhibited. Insulin-mediated vasodilation was inhibited by an intrafemoral artery infusion of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase. During the study, leg blood flow (LBF) and arteriovenous glucose difference (AVG delta) were measured every 10 min; leg glucose uptake (LGU) was calculated as LGU = LBF x AVG delta. The systemic insulin infusion caused a time-dependent increase in LBF from 0.194 +/- 0.024 to 0.349 +/- 0.046 l/min (P < 0.01). The intrafemoral artery infusion of L-NMMA completely inhibited this increase in LBF. AVG delta, LGU, and whole body glucose disposal rates increased in a time-dependent manner in both studies. The maximum AVG delta was lower with insulin-mediated vasodilation intact than when inhibited (25.9 +/- 2.5 vs. 35.0 +/- 1.6 mg/dl, P < 0.001). The time to achieve half-maximal (T1/2) AVG delta was somewhat longer with insulin-mediated vasodilation intact compared with inhibited (35.6 +/- 4.1 vs. 29.7 +/- 1.6 min, P < 0.01). Maximal LGU was 93.9 +/- 26.8 and 57.2 +/- 11.6 mg/min (P < 0.005), and the T1/2 LGU was 50.2 +/- 16.0 and 36.3 +/- 8.8 min (P = 0.1) during intact and inhibited insulin-mediated vasodilation, respectively. Thus insulin-mediated vasodilation has a modest effect in slowing the time course at which insulin stimulates glucose uptake but has a marked effect in augmenting the maximal rate of insulin-stimulated glucose uptake in skeletal muscle. Impaired insulin-mediated vasodilation, as observed in patients with essential hypertension, may explain, at least in part, the insulin resistance observed in these patients.

Adult↗

Nitrovasodilator repletion increases TNF-alpha-induced pulmonary edema.

We tested the hypothesis that nitrovasodilator repletion enhances tumor necrosis factor-alpha (TNF-alpha) -induced pulmonary edema. Lungs were isolated from control guinea pigs or 4 h after the intraperitoneal injection of TNF-alpha (1.60 x 10(5) U/kg). In the control and TNF-alpha-injected lungs, the thromboxane mimetic U-46619 (155 pmol/min) caused increases in pulmonary capillary pressure (Ppc) and lung weight (delta W). In control lungs, the nitrovasodilator agonist S-nitroso-N-acetyl-penicillamine (SNAP, 1 microM) attenuated the U-46619-induced increases in Ppc. In lungs injected with TNF-alpha, SNAP had no effect on Ppc and increased delta W. The peroxynitrite (ONOO-) scavenger urate (35 mM) prevented the TNF-alpha +SNAP-induced increases in Ppc and delta W. In addition, chemically synthesized ONOO- (4.0 mM) enhanced U-46619-induced increases in delta W. The data indicate that nitric oxide repletion enhances TNF-alpha-induced pulmonary edema, possibly via ONOO-.

Animals↗

ECG changes in pediatric patients on tricyclic antidepressants, desipramine, and imipramine.

OBJECTIVE: To determine if there is an altered pattern of cardiac electrical activity in children treated with tricyclic antidepressants, desipramine, or imipramine, which may predispose these patients to sudden death. METHODS: All patients in a child psychiatry practice from 1989 to 1993 in Calgary, Alberta, treated with desipramine or imipramine with both pre- and post-treatment electrocardiograms (ECGs) were included in the study (n = 21; ages 8 to 17 years). Thirty-six blinded post-treatment ECGs were analysed for interval measurement and compared to the pretreatment ECGs. RESULTS: Drug dosages ranged from 25 mg to 125 mg per day and treatment duration ranged from 1 to 49 months. Seven of 21 patients were concurrently receiving an antipsychotic medication (pericyazine). The maximal increase in PR, and QRS, and QT interval changes were 40 msec and 70 msec, respectively, with most patients demonstrating no significant changes in the ECG intervals. The QT interval was corrected for heart rate (QTc). No significant arrhythmias or tachycardias were observed. ECG interval changes were not related to drug dosage, age, treatment duration or plasma levels. CONCLUSIONS: No consistent pattern of ECG interval changes including the QTc interval was observed in children on desipramine and imipramine.

Adolescent↗

Birthweight and health and development at the age of 7 years.

This study was set up to compare the frequency of health, educational and behavioural problems in a geographically defined birth cohort of 7-year-old children grouped by weight at birth. The study design was based on a multi-stage postal survey, with sampling stratified by birthweight. It took place in the four counties of Oxfordshire, Buckinghamshire, Berkshire and Northamptonshire which make up the former Oxford region. We studied 1319 live births to women resident in the former Oxford region in 1985, including all those with birthweights under 1500 g, or whose weight was not recorded, and a sample of those who weighed 1500-2499 g, and of those who weighed 2500 g or more at birth. The children in the sample were traced through the National Health Service Central Register (NHSCR) and self-administered questionnaires were sent to their parents, general practitioners (GP) and teachers. Of the 1169 children who were alive at the age of 7 years and were successfully traced, 805 (75%) were followed up by postal survey. The use of health services, and of additional educational support was higher, and school performance was poorer among children who had weighed less than 1500 g at birth than among children who had weighed 2500 g or more, with the rates for children who had weighed 1500-2499 g falling in between. This survey method identifies the higher rate of health and educational problems in children weighing under 2500 g at birth, particularly those with birthweight under 1500 g, compared with other children. The method could be developed to provide a way of monitoring any changes over time in the prevalence of these problems. This information can be used to assess the health and educational needs of 7-year-old children in the population.

Adult↗

Pregnancy in patients with preexisting transverse myelitis.

BACKGROUND: Although several cases of pregnancies of traumatic spinal cord injury patients have been reported, to our knowledge, only one case has been reported detailing the perinatal outcome in a patient with preexisting transverse myelitis. CASE: The prenatal course and pregnancy outcome in two patients with preexisting transverse myelitis is presented. The major complications encountered were urinary tract infections and mobility problems. CONCLUSION: Patients with preexisting transverse myelitis can have successful pregnancies with term vaginal deliveries. Prevention of potential complications, such as anemia, preterm labor and delivery, decubitus ulcers, and autonomic dysreflexia can be achieved with coordinated multidisciplinary management.

Adult↗

Study of in vitro and in vitro effects of isradipine in skeletal muscles and interaction with some drugs.

The effects of the calcium channel blocker isradipine were studied in the indirectly and directly stimulated mouse diaphragm and in the anesthetized rat to determine its potency, reversibility and interaction with a number of drugs. Initially, it potentiated both indirect and direct twitches followed by a reduction. With tetanic contractions, no potentiation was obtained, only a reduction, which was complete or near complete at the highest concentration tested (10(-4) M). In combination, isradipine reduced the IC50 and IC90 values for the antibiotics gentamicin, polymyxin B and clindamycin, d-rubocurarine and magnesium ions. Depression of contraction caused by isradipine or in combination could be reversed to varying degrees by washout, elevated calcium ions, neostigmine or 4-aminopyridine. Spontaneous recovery from the effects of isradipine alone or in combination was slow and usually incomplete. For in vivo experiments, severe cardiovascular depressant effects of isradipine limited its exposure to lower concentrations and for shorter periods. Under these conditions, it had no effect on heart rate. However, both systolic and diastolic blood pressure were significantly reduced, while pulse pressure was increased. After an initial potentiation muscle contraction was maximally reduced to 55% of control. This study indicates that acute administration of isradipine may aggravate neuromuscular effects of antibiotics, muscle relaxants or hypermagnesemia, although it is unlikely that spontaneous recovery or reversibility of muscular activity by suitable reversal agents will be affected. However, prolonged use of the drug may be more difficult to reverse.

Animals↗

The effect of reduction of lipoprotein (a) on cellular cholesterol synthesis in non-diabetic and type 2 diabetic subjects.

This study investigates the effect of Lipoprotein (a) (Lp(a)) on cellular cholesterol synthesis in non-diabetic (n = 7) and Type 2 (non-insulin-dependent) diabetic subjects (n = 7) with elevated levels of Lp(a) (> 20 mg/dl). N-Acetylcysteine was used to lower Lp(a) in the control subjects and their lipoproteins were re-examined after 7 days of treatment. Low-density lipoprotein (LDL) was isolated and separated from Lp(a) by sequential ultracentrifugation. Regulation of cellular cholesterol synthesis was assessed by measuring incorporation of [14C]acetate into mononuclear leucocytes in the presence of LDL and Lp(a). Cellular cholesterol content was determined by a fluorometric assay. Delivery of cholesterol to the cell was examined using [3H]cholesteryl oleate-labelled LDL or Lp(a). LDL (5 micrograms/ml) from non-diabetic subjects suppressed cellular cholesterol synthesis by 66.2%, while Lp(a) at a similar concentration only suppressed cholesterol synthesis by 5.8% (P < 0.001). At a concentration of 20 micrograms/ml, Lp(a) suppressed cholesterol synthesis by 31.7%. The situation was similar in the diabetic subjects. Serum LDL cholesterol in non-diabetic subjects was 4.2 +/- 0.5 mmol/l and the LDL esterified/free cholesterol ratio was 2.6 +/- 0.2. Following treatment with N-acetylcysteine, LDL cholesterol did not change, while Lp(a) decreased significantly by 24% (P < 0.05). The LDL esterified/free cholesterol ratio decreased to 2.2 +/- 0.2 (P < 0.05) and there was a significant increase in the ability of the subjects LDL to inhibit cellular cholesterol synthesis (P < 0.05). There was a significant negative correlation between plasma Lp(a) and the ability of the patients' LDL to inhibit cellular cholesterol synthesis (r = -0.68, P < 0.01). [3H]Cholesteryl-oleate-LDL (5 micrograms/ml) delivered 266 +/- 13 ng cholesteryl oleate/mg cell protein, while it took 20 micrograms of [3H]cholesteryl oleate-labelled-Lp(a) to deliver a similar concentration (315 +/- 21 ng cholesteryl oleate/mg cell protein). In conclusion it appears possible that the atherogenicity of Lp(a) may be associated with its effect on the LDL receptor which alters LDL receptor uptake, LDL composition and cellular cholesterol synthesis.

Acetylcysteine↗