Biomedical subjects
Publications and source records attributed to A G Howatson.
Benign tumors of the thymic gland are relatively rare. Although most of these lesions are asymptomatic in nature, they may result in respiratory distress. This report describes 2 cases of benign thymic tumors presenting with respiratory symptoms that resolved after operative excision.
Analyses of survival data of neonates born with congenital diaphragmatic hernia (CDH) can be misleading. There is a hidden mortality only apparent when fetuses with CDH are included in the analysis. A retrospective review of all post mortems with a diagnosis of CDH in the West of Scotland over a 10-year period was carried out. Congenital anomalies were identified and heart and lung weights were compared with controls (infants dying of non-cardiorespiratory causes). 70 Pm reports were studied. Major congenital anomalies were present in 53% (18/ 47 live born, 19/23 not live born). Neural tube defects, cardiac and chromosomal anomalies were the most common. Antenatal detection rate was 17% in live-born infants. In infants dying within the first week of life lung weights showed severe pulmonary hypoplasia, but heart weights were within the normal range. Detailed antenatal scanning needs to be considered if the detection rate for CDH is to improve in this region.
Explore the source record for details and available documents.
CT-guided percutaneous lung biopsy was performed in children with chronic respiratory disease to obtain samples for histological examination. An automatic cutting device with a 14-G needle was used with one or two cores obtained in each procedure. Seven procedures were performed in six children, mostly with local anaesthesia. Adequate tissue was obtained in all cases. Although a small pneumothorax and/or haemothorax occurred in most procedures, these were usually visible only on CT and did not require active management. A larger pneumothorax in one child also resolved with conservative management. Percutaneous CT-guided 14-G automatic cutting-needle biopsy of lung parenchyma in children is a minimally invasive alternative to open-lung biopsy with no complications in our series.
There is little evidence as to the fatty acid composition of the cerebellum in infancy and it remains uncertain whether milk diet can influence its composition. We therefore examined cerebellar gray and white matter of infants less than 6 month old who had died unexpectedly. The fatty acid content of 33 gray and 21 white matter specimens from infants born at term and 6 gray and 5 white matter specimens from preterm infants was assessed by gas chromatographic/mass spectrometric analysis. Infants were grouped according to whether they had received human or manufactured formula milk. Whereas cerebellar cortex docosahexaenoic acid (DHA, 22:6n-3) concentrations were significantly lower (P<0.01) in the formula-fed than breast-fed infants, no differences existed between the term (n = 10) and preterm (n = 5) Synthetic Milk Adapted [corrected] (SMA) formula-fed infants. Cerebellar white matter DHA concentrations were similarly lower (P<0.01) in the SMA formula-fed infants (n = 8) than in an age-matched breast-fed group. Low concentrations of cerebellar white matter lignoceric (24:0) and nervonic acid (24:1n-9) in two 7-wk-old preterm infants appeared to correlate with postgestational rather than chronological age. Dietary long-chain polyunsaturated fatty acids, particularly DHA, are probably essential for normal development of the infant cerebellum.
One hundred and fifty-seven liver samples from newborns and infants who had died from sudden infant death syndrome (SIDS) or other known causes have been analysed by ICP-MS for Ag, Cd, Co, Pb and Sb. The median concentrations found were: 15.4 (Ag), 2.9 (Cd), 15.9 (Co), 65.2 (Pb) and 1.8 (Sb) ng g-1 wet mass. There was no measurable difference in the concentrations of any of these elements between the SIDS and non-SIDS groups. The validity of the results was assessed by analysis of appropriate reference materials, interlaboratory comparison and isotope dilution analysis. The instrumental limits of detection were 0.25 (Ag), 0.14 (Cd), 0.21 (Co), 3.8 (Pb) and 0.38 (Sb) ng g-1 wet mass. The limits of detection of the method depend on the reagent blank and the extent of background contamination.
BACKGROUND: Intrauterine growth restriction (IUGR) has been linked to impaired renal function and hypertension, suggesting that an adverse prenatal environment could alter kidney development and renin production. METHODS: Immunohistochemistry and in situ hybridization were employed to localize renin-containing cells (RCCs) in the deep, middle, and superficial zones of autopsy kidney sections, in parallel with histologic maturation, from unexplained stillborn fetuses of normal weight (N = 26) and stillborn fetuses with IUGR (N = 17). RESULTS: In the control group, the number of RCC per 100 glomeruli in the deep zone decreased with advancing gestation from 40 at 20 weeks gestation to five at term (P < 0.001), whereas the opposite change was found in the superficial zone (increase from 5 per 100 to 55 per 100; P < 0.001). In the IUGR group, the density of RCCs in both the superficial and deep zones was similar to the control group at 20 weeks, and no shift in renin gene expression was observed as gestation advanced. Histologic maturation was unaltered. CONCLUSIONS: Renin gene expression persists and predominates in the deep renal cortex of the stillborn IUGR fetus, and could contribute to the pathogenesis of neonatal oliguria and/or hypertension during postnatal life.
We examined the incidence, aetiological factors and outcome in 40 cases of nonimmune hydrops fetalis (NIH) and suggest a rational approach to management. The incidence of NIH was 1 in 830 deliveries during the last 10-year period. In spite of extensive antenatal and postnatal investigation no cause could be established in 14 (35%) cases. A probable aetiological factor was found in 65% of cases. These included viral infection (7), cardiovascular (6), twin-to-twin transfusion (3), chromosomal abnormality (3), other malformation syndromes (4), renal dysplasia (1), laryngeal atresia (1) and severe fetomaternal haemorrhage (1). Five of the 40 fetuses survived, 2 treated antenatally for tachyarrhythmia, 2 had spontaneous resolution and the fifth fetus had repeated intrauterine transfusions because of human parvovirus B19-induced anaemia. After diagnosis of nonimmune hydrops fetalis, early referral to a tertiary centre is to be encouraged for investigation and provision of intensive perinatal care. Investigation allows parents to be counselled appropriately that the mortality is no longer 100% and a steadily growing number may be amenable to some form of fetal therapy.
Abnormal fetal and infant growth have increasingly been correlated with adult onset cardiovascular disease. To date, there is little known about the lipid fatty acid profiles in infant cardiovascular tissue. Therefore, we analysed total lipid fatty acids from thoracic and abdominal aorta intima and media from 24 normally grown sudden infant death syndrome cases. Aorta from small for gestational age (n = 2), failure to thrive from birth (n = 3), and premature (n = 1) infants were also examined. Dihomo-gamma-linolenic acid (C20:3n-6) and oleic acid (C18:1n-9) concentrations were significantly lower in the thoracic than in the abdominal aorta. Similar dietary related differences were found in the subgroup (n = 15) of infants fed on formula milks. Both abdominal and thoracic intimal arachidonic (C20:4n-6) to dihomo-gamma-linolenic acid ratios were greater in the infants with retarded growth after birth than in their normally grown counterparts. Growth restriction in infancy might disrupt the normal accretion of vascular endothelial polyunsaturated fatty acids.
We report on 12 children with neuronal ceroid lipofuscinosis (NCL) diagnosed between 1974-1995 in the West of Scotland. Diagnosis was made on the basis of clinical, electrophysiological, radiological and pathological examination including electron microscopy (EM) in all cases. Incidence was calculated on the basis of the year of diagnosis and the live birth rate. Six cases were infantile and 6 juvenile NCL derived from a total of 10 families. No cases of late infantile or early juvenile NCL were identified. All cases were typical in clinical description. Cumulative incidence was 1.61/100,000 live births (0.87 and 0.73/100,000 live births for juvenile and infantile NCL respectively). There was significant delay in diagnosis of the juvenile form of NCL. EM findings were unusual in the juvenile group in that 5 of 6 cases exhibited granular osmiophilic deposits (GROD) rather than typical fingerprint inclusion bodies. Four of these 5 cases also failed to show vacuolation of lymphocytes. Thus, in the West of Scotland, the distribution of NCL cases by type and by EM findings is unusual, and suggests a distinct genetic variant of juvenile NCL, possibly allelic to infantile NCL.
Atypical mycobacterial (AMB) infection is an important cause of lymph node enlargement in children. Over the period, January 1992 to December 1993, 17 patients with lymphadenitis because of AMB infection were treated at the Royal Hospital for Sick Children in Glasgow. These case notes of the patients were reviewed. The mean age at presentation was 5.37 years (range 1.5-10.6 years). The patients had a short history (1-11 weeks) of unilateral single focus, usually cervicofacial (16/17), disease. The tuberculin skin test was not helpful in diagnosis (negative in 14/15). Primary excision was curative (11/11). Incision and drainage of an abscess or drainage with partial excision led to chronically discharging sinus in all cases (6/6). AMB were not always seen on staining (11/17) of drained or excised material and cultures were negative in eight cases. The diagnosis in the remaining patients was made on the basis of clinical features and particular histopathological patterns. We are currently assessing the use of polymerase chain reaction (PCR) techniques for making the diagnosis in non-cultured cases.
Using biochemical and immunocytochemical methods, we have investigated endogenous levels of various markers in tissues obtained from 67 Down's syndrome pregnancies after therapeutic abortion in the second trimester and in corresponding tissues from unaffected abortuses. Alpha-fetoprotein (AFP), intact and free beta human chorionic gonadotrophin (hCG), pregnancy-specific beta-1 glycoprotein (SP-1), placental alkaline phosphatase (PALP), pregnancy-associated plasma protein A (PAPP-A), and gamma glutamyl transferase (GGT) were investigated in placental tissue; AFP and GGT in fetal liver; and GGT in fetal intestine. The results indicate that maternal serum levels of placental products reflect those found in the placenta: intact hCG, free beta hCG, and SP-1 levels were elevated in Down's syndrome pregnancies, while PAPP-A and PALP levels were little changed. This suggests that membrane passage of these markers is not affected but there is altered synthesis of hCG and SP-1. AFP levels were strikingly elevated in placental homogenates and unchanged in liver homogenates from Down's syndrome pregnancies, while the levels in maternal serum were reduced, pointing to a possible transport defect specific to AFP. GGT levels were high in placenta and liver from Down's syndrome pregnancies but low in fetal intestine.
Explore the source record for details and available documents.
Most patients with nephroblastoma have high levels of plasma renin and some are hypertensive. Blood pressure falls after removal of the affected kidney, suggesting that nephroblastoma is associated with renin production either by the tumour or by the kidney. In this study, direct evidence was sought of renin gene expression in nephroblastoma using in situ hybridization. Digoxigenin-labelled riboprobes and an immunoperoxidase technique were used to detect cells containing renin mRNA: this showed renin gene expression in 9 out of 12 cases. There were positive cells within metanephric blastema and in occasional neoplastic glomeruloid structures, confirming that in seven cases nephroblastoma tumour cells expressed the renin gene. However, renin gene expression was also demonstrated in perivascular cells of uncertain lineage in seven cases; in five cases there was evidence of renin gene expression in both tumour cells and perivascular cells. The latter finding raises the possibility that some of the cells expressing the renin gene could be stromal cells. It is concluded that nephroblastomas contain cells that express the renin gene and that some are tumour cells, while other perivascular cells may be stromal cells.
Explore the source record for details and available documents.
A dietary-related deficiency of docosahexaenoic acid [C22:6(n-3)] in infant cerebral cortex has been identified. Absence or very low rates of hepatic synthesis from the essential fatty acid precursor, alpha-linolenic acid [C18:3(n-3)], in early life may have been a contributory factor. We have analyzed liver total lipid fatty acid compositions in 27 term (37-42 wk gestation) and 4 preterm (30-33 wk gestation) infants who died within the first 6 mo of life from sudden infant death syndrome. The infants were fed exclusively either human or formula milks. Formula-fed infants were subdivided into two groups, one receiving SMA milk with an alpha-linolenic acid content at 1.5% of total fatty acids and the other a composite group fed milks with low alpha-linolenic acid concentrations (< 0.1% to 0.4%). The hepatic content of arachidonic acid [C20:4(n-6)] and docosahexaenoic acid was generally lower in both formula-fed groups than in the human milk-fed group. The age-related distributions of docosahexaenoic acid showed that coincident minimum levels were present in both formula groups in the third month of life. This may indicate that the hepatic enzymes involved in the final stage (delta 4-desaturation) conversion of alpha-linolenic acid to docosahexaenoic acid could be inactive in the first months of life. Emphasis must be on provision of preformed dietary docosahexaenoic acid and possibly arachidonic acid as well as their essential fatty acid precursors, to both term and preterm infants for at least the first 16 wk of life.
BACKGROUND: Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may lead to inflammation of the small intestine associated with occult blood and protein loss. The aim of this study was to investigate the prevalence and structural correlates of this enteropathy. METHODS: We examined the stomach, duodenum, and small intestine of 713 patients post mortem. Of these patients, 249 had had NSAIDs prescribed during the six months before death and 464 patients had not. All visible small intestinal lesions were removed for histologic examination, and specific etiologic factors were sought. The prevalence of nonspecific small-intestinal ulcers and ulcers of the stomach and duodenum was compared in the two groups of patients. RESULTS: Nonspecific small-intestinal ulceration was found in 21 (8.4 percent) of the users of NSAIDs and 3 (0.6 percent) of the nonusers (difference, 7.8 percent; 95 percent confidence interval, 5.0 to 10.6 percent; P less than 0.001). Three patients who were long-term users of NSAIDs were found to have died of perforated nonspecific small-intestinal ulcers. Ulcers of the stomach or duodenum were found in 54 (21.7 percent) of the patients who used these drugs and 57 (12.3 percent) of those who had not (difference, 9.4 percent; 95 percent confidence interval, 3.9 to 15.1 percent; P less than 0.001). CONCLUSIONS: Patients who take NSAIDs have an increased risk of nonspecific ulceration of the small-intestinal mucosa. These ulcers are less common than ulcers of the stomach or duodenum, but can lead to life-threatening complications.
Conventional approaches to virus detection fail to provide convincing evidence in support of a viral aetiology for SIDS. Virus positivity of about 20% in cases of SIDS is typical of most studies and is similar to that found in control groups. The application of direct immunofluorescence assays (DFA) has increased virus detection rates to 30-40%. Constraints imposed by technology, postmortem interval, choice of samples for analysis and the necessary limitation of virus types to be sought may all result in under-diagnosis of virus positivity. Alpha interferon (IFN alpha), produced by cells in an early response to exposure to many viruses, has been shown to increase in concentration in the cerebrospinal fluid of patients with viral meningitis. In cases of SIDS significant increases in IFN alpha concentrations have been shown in nasopharyngeal aspirates from virus positive cases and from apparently virus negative cases. The application of conventional techniques of DFA and IFN alpha measurement therefore identifies a much larger percentage of SIDS cases as having been exposed to virus. Disturbance of respiratory regulation has been suggested as an aetiological mechanism in SIDS. Apnoeic episodes are frequently described and are known to be associated with certain viral infections, particularly respiratory syncytial virus. The abnormal presence of IFN alpha in neurones of the medulla of the brain stem in a proportion of SIDS cases were identified by immunohistochemistry. This might suggest a link between viral infection and disturbance of respiratory regulation. The higher rates of virus exposure which can now be detected and the localisation of IFN-alpha in medullary neurones suggest that it is premature to discount the viral hypothesis as an explanation for at least a proportion of SIDS cases.