Community paediatrics moves on—an analysis of changing work patterns 1994–97

Objectives: To describe the current clinical workload of the modern community paediatrician; to outline the changes in this role over recent years and examine the reasons for these.Design and setting: The design is a retrospective analysis of data routinely collected for contracting purposes. Nottingham community paediatric service 1994–97 is the setting.Main outcome measures: These are the characteristics of patients seen, sources of referral, locations of clinical contact, referral rates by area.Results: 36 710 appointments were offered over the time period studied. The non-attendance rate was 17%. Pre-school children made up the largest group seen. Most referrals were from health visitors (23%) and school nurses (29%). There has been a small but significant increase in the numbers of children seen who have developmental problems and disability, and due to child protection issues between the time periods. There has been a shift in the proportions of children seen in a local health centre referral clinic (9.8% increase during 1994–97) rather than in a school setting. Twice as many children are referred to the community paediatrician from inner city areas than from the surrounding county areas.Conclusion: The transfer of child health surveillance to the primary health care team and the increased training of community paediatricians, has resulted in community paediatricians developing an increasingly specialised role particularly in the areas of child growth and development, disability, social and behavioural paediatrics.Public Health (2000) 114, 61–64.     

Surveillance of invasive infection in children and adults admitted to QECH,Blantyre, 1996–2002

This is a report of blood CSF isolates from the adults medical and paediatric of wards QECH, Blantyre, cultured and identified at the Welcome Trust Research Laboratories during 1996–2002. The commonest causes of adults and children bacteraemia were non-typhoidal Salmonella (35% of all blood isolates for adults and children) and Streptococcus pneumoniae (14% and 13% respectively). Cryptococcus neoformans was the commonest isolates from CSF of adults with meningitis(67%) but was very rare in children. S.pneumoniae was the commonest cause of bacterial meningitis in children and adults (38% and 28% of all CSF isolates respectively). Haemophilus influenzae type b was also a common cause of meningitis in children (27%). Data of in vitro antibiotic sensitivity are also reported. A major concern is the recent marked rise of chloramphenicol resistance among Salmonella enteritidis and Salmonella typhimurium to over 80% resistance.     

Non-insulin-dependent diabetes mellitus: dietary monounsaturated fatty acids and low-density lipoprotein composition and function

Alterations in low-density lipoprotein (LDL) composition in diabetes affect its function with respect to control of de novo cholesterol synthesis. We examined the effect of 4 weeks of an oleic-acid-rich diet on LDL composition and function in eight Type 2 diabetic and eight non- diabetic control subjects. LDL (density 1.019-1.063 g/l) was isolated by sequential ultracentrifugation. LDL composition was measured and LDL fatty acids were determined by gas liquid chromatography. Cholesterol synthesis was measured by [14C]-acetate incorporation into the freshly isolated mononuclear leucocytes. Fasting blood glucose fell from 9.3 +/- 2.0 to 8.2 +/- 1.2 mmol/l (p < 0.05) and fasting serum insulin increased from 8.3 +/- 2.8 to 10.4 +/- 5.0 mIU/l (p > 0.05) in the diabetic patients. LDL oleic acid increased in the diabetic patients from 18.8 +/- 1.8% to 22.5 +/- 1.9% (p < 0.01) and in the non-diabetic subjects from 19.9 +/- 1.8% to 23.3 +/- 2.8% (p < 0.01). The LDL- esterified to free cholesterol ratios of 3.0 +/- 0.6 and 2.7 +/- 0.2 for the diabetic and non-diabetic patients were similar, and decreased significantly (p < 0.01) to 2.4 +/- 0.5 and 2.2 +/- 0.4, respectively. Baseline [14C]-acetate incorporation was similar in the two groups, and decreased after diet from 437 +/- 239 to 249 +/- 144 ng/g cell protein (p < 0.05) in the diabetic patients. There was a negative correlation between the LDL-esterified to free cholesterol ratio and the ratio of oleic to linoleic acid in the LDL (r = -0.39, p < 0.05) and a negative correlation between fasting blood glucose and LDL oleic acid in the diabetic patients (r = -0.51, p < 0.05). Enrichment of LDL with oleic acid appears to improve its ability to regulate endogenous cholesterol synthesis in both control and diabetic subjects. In the diabetic population, the diet had a favourable effect on glycaemic control.      

Immunohistochemical localization of hepatic nitric oxide synthase in normal and transgenic sickle cell mice: the effect of hypoxia

Nitric oxide (NO) generated from L-arginine and molecular oxygen by nitric oxide synthase (NOS) has been shown to influence hepatocellular function and pathology in response to ischemia and certain hepatotoxins. In the present study, we examined the liver of a transgenic line of sickle cell mice for hepatocellular injury and localization of two isoforms of NOS, the endothelial constitutively expressed isoform (EcNOS) and the inducible isoform (iNOS) by immunohistochemistry. Diffuse expression of EcNOS was observed in hepatocytes of control and sickle cell animals maintained under room air conditions. In contrast, iNOS was observed only in the sickle cell mice, well-localized to hepatocytes surrounding the central veins of the lobules. When normal mice were exposed to hypoxic conditions for 4 to 5 days, iNOS immunostaining appeared de novo in a patchy distribution throughout the liver lobules. In the sickle cell mice, hypoxia appeared to increase the subjective intensity of pericentral staining of iNOS. Liver histology was normal in the sickle cell mice maintained under room air conditions, but showed multifocal areas of necrosis when sickling was exacerbated by chronic hypoxic conditions. However, a pericentral zone of preserved architecture was present, corresponding to the region of iNOS staining. We postulate that pericentral induction of iNOS under ambient conditions occurs in transgenic sickle cell mice in response to particularly intense hypoxic conditions near the central veins of the liver. Increases in NO synthesis may occur in this region, which would serve to protect these cells from ischemic damage either directly or by maintaining blood flow. These findings could be relevant to liver pathophysiology in patients with sickle cell disease.     

Blood safety decisions, 1982 to 1986: perceptions and misconceptions

Although blood bankers and those who treat persons with hemophilia are supportive of most of the recommendations of the Report, the manner in which the analysis was conducted and some of the general conclusions that were reached appear flawed. The flaws may reflect the deficiencies in the process by which the Committee gathered data more than any bias on the part of its members themselves. The Report may accurately reflect the testimony heard, but it is biased by the committee's acceptance as fact the opinions of critics who claim the AIDS epidemic was mismanaged by the blood-collecting agencies, professional organizations, hemophilia organizations, and the federal government. Countervailing views on the various issues are ignored or incompletely discussed. Much testimony was taken from the victims of the transfusion- associated AIDS epidemic. Reliance seems to have been placed upon hindsight testimony (taken 10 years after the events), rather than on documentation of what was known at the time when events unfolded. The Report states that "[t]he Committee's charge did not include the development of assertions about what should have been done at the time," l(pl:4) yet that is precisely what was done. These comments address just a few of the misconceptions we perceive in the Report. They are based on our understanding of the state of knowledge–or ignorance–at the time that decisions about the safety of the blood supply were made. If we are to avert future threats to the blood supply from emerging infectious diseases, a goal that is universally embraced, we must learn the lessons the past can teach us, as painful as they may be. However, the hazards of judging history in hindsight should be avoided. Neither allegations nor opinions should be accepted as facts without critical examination and without placement in the context of contemporary knowledge; to accept a lesser standard does a great injustice to all who were touched by this tragedy.     

Mutations disrupting extracellular structure of MPZ cause early onset severe forms of CMT1B

Missense mutations in myelin protein zero (MPZ), an important molecule for myelin compaction, cause inherited neuropathies collectively referred to as CMT1B. Depending on the mutation, phenotypes can be severe, or mild. To determine genotype‐phenotype correlations in CMT1B we evaluated patients from 11 different families seen in our clinic and 80 reported cases from the literature with respect to (1) how the mutation affected amino acids known to be critical for homotypic MPZ interactions; (2) whether the mutation affected the charge or hydrophobicity of an amino acid; (3) whether the mutation was likely to affect the secondary or tertiary structure of the MPZ, or (4) whether it affected evolutionarily conserved amino acids. We found that mutations that added a charged residue to the extracellular domain, introduced a cysteine or altered a conserved amino acid, caused a severe neuropathy. Mutation of an amino acid critical for cis or trans homotypic adhesion, however, had no obvious consequences on disease severity. We conclude that mutations which significantly disrupt the secondary or tertiary structure of MPZ are likely to cause severe, early onset neuropathies, whereas mutations which do not cause milder disease. Studies on how mutations disrupt protein trafficking and adhesion are underway.     

Unusual cutaneous carcinoma with features of small cell (oat cell-like) and squamous cell carcinomas. A variant of malignant Merkel cell neoplasm

Three unusual primary neoplasms in the skin that occurred in elderly patients (64, 77, and 69 years of age) are presented. Two histologic components were found in each of the three neoplasms, one being small cell or oat cell-like carcinoma and the other squamous cell carcinoma. Study by electron microscopy revealed neurosecretory granules, though few, in the small cell component. The lack of clinical evidence of oat cell carcinoma elsewhere, the autopsy finding of two histologic components in one patient, and the findings by conventional and electron microscopy lead us to conclude that these three neoplasms are primary in the skin and of Merkel cell origin. We suggest further that small cell carcinoma of the skin represents a poorly differentiated counterpart of trabecular carcinoma. The spectrum of malignant Merkel cell neoplasm is, therefore, expanding. Two of our three patients died of their neoplasms 2 and 2 1/2 years, respectively, after the initial diagnosis.