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1.  Use of recombinant human parvovirus B19 antigens in serological assays. 
Journal of Clinical Pathology  1993;46(9):840-845.
AIMS--To compare the sensitivity, specificity, and practicality of recombinant proteins in serological tests for the detection of human parvovirus B19 IgG and IgM. METHODS--Indirect enzyme linked immunosorbent assays using B19 structural proteins expressed in Escherichia coli were developed for the detection of B19 specific IgG and IgM (rELISA-G and rELISA-M). Cells infected with baculovirus expressing B19 structural proteins were also used in an indirect immunofluorescence assay for IgG and IgM antibodies (IFA-G and IFA-M). Antibody capture radioimmunoassays for IgG and IgM (GACRIA and MACRIA) were used as comparative assays. RESULTS--Twenty nine pools of intravenous immunoglobulin were clearly positive for B19 IgG by rELISA-G and contained low IgG titres by GACRIA. From 113 samples tested by all methods, sensitivities of 92% (77/84) and 97% (68/70) were obtained for ELISA and immunofluorescence, respectively, when compared with GACRIA. One hundred and sixteen samples from patients presenting with rash or arthralgia were compared by MACRIA, rELISA-M, and IFA-M. Sensitivities of both recombinant tests were more than 95%. Despite pretreatment to remove IgG or rheumatoid factor, false positive results were a problem in the rELISA-M but were not seen with the IFA-M. CONCLUSIONS--The limited supply of native antigen has severely restricted the wide application of serology for parvovirus B19. The use of recombinant antigens permitted the introduction of local screening tests which had many advantages, including quicker results and relief of the burden on the Reference Laboratory. The use of rELISA-M for sensitivity and IFA-M for specificity and confirmation proved a useful and practical combination for diagnosis of recent infection with B19, and rELISA-G allowed the immune response to be determined in selected populations.
PMCID: PMC501521  PMID: 8227436
2.  Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction. 
BMJ : British Medical Journal  1996;312(7047):1637-1641.
OBJECTIVES--To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. DESIGN--Cohort follow up study. SETTING--The four coronary care units in Auckland, New Zealand. SUBJECTS--All 3014 patients presenting to the units with suspected myocardial infarction in 1993. MAIN OUTCOME MEASURES--Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation > or = 2 mm in leads V1-V3, ST elevation > or = 1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. RESULTS--948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. CONCLUSIONS--On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high.
PMCID: PMC2351378  PMID: 8664716
3.  Effects of streptokinase in patients presenting within 6 hours of prolonged chest pain with ST segment depression. 
British Heart Journal  1995;73(6):500-505.
BACKGROUND--The effects of streptokinase on the occurrence of a combined clinical outcome in patients presenting with recent chest pain and ST depression were investigated in view of the role of thrombus in the pathogenesis of acute ischaemic syndromes. METHODS--112 patients aged < or = 75 years presenting within 6 h of the last episode of ischaemic chest pain of least 20 min duration with > or = 1 mm ST depression were randomised in a double blind manner to receive either streptokinase 1.5 million units over 30 min (n = 57) or placebo (n = 55). The primary end point was the combination of death, frequency of myocardial infarction (defined as peak creatine kinase > 600 U/ml), need for angiography because of uncontrollable ischaemia, and an exercise test within 35 days showing > or = 1 mm ST depression at < or = 6 min. The secondary end points were safety, frequency of chest pain, readmission with myocardial infarction or unstable angina, or need for revascularisation between 35 days and 1 year. The severity of ST depression on presentation was analysed with respect to clinical outcome. RESULTS--The frequency of the combined hierarchical end point of death, myocardial infarction, early angiography, and a positive exercise test was 82% (47 of 57 patients) with streptokinase and 75% (41 of 55 patients) with placebo. There were four deaths, two in each group. 27 patients (47%) receiving streptokinase and 22 (40%) receiving placebo developed myocardial infarction. 11 patients (eight streptokinase and three placebo) required coronary arteriography and subsequent revascularisation because of angina uncontrolled by medical treatment. 44 patients (22 in each group) had a positive exercise test. There were three further cardiac deaths (one streptokinase, two placebo), and three noncardiac deaths within 1 year. A conservative approach to intervention was adopted and over a period of 1 year 29 patients (26%) (13 streptokinase and 16 placebo) underwent revascularisation procedures. Three patients (two streptokinase and one placebo) required transfusion. ST depression > or = 3 mm had 90% specificity but only 60% positive predictive value for myocardial infarction at presentation (P = 0.008, stepwise logistic regression). ST depression > or = 2 mm was predictive of death, late development of myocardial infarction, or a need for angiography (P = 0.02). CONCLUSION--Patients presenting with ischaemic chest pain and ST depression frequently develop myocardial infarction. Severe ST depression is predictive of an adverse outcome. The 35 day (3.6% cardiac and total) and 1 year mortality (8.9% total, 6.3% cardiac) are low with conservative management and expeditious revascularisation. Streptokinase treatment within 6 h of the last episode of pain does not seem to be beneficial.
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PMCID: PMC483908  PMID: 7626346
4.  Cefepime compared with ceftazidime as initial therapy for serious bacterial infections and sepsis syndrome. 
In an open randomized multicenter comparative study, we evaluated the safety and efficacy of cefepime (CP; 2.0 g given intravenously every 12 h) and ceftazidime (CZ; 2.0 g given intravenously every 8 h) as initial treatment for adult patients with suspected serious bacterial infections. A total of 133 patients entered the study, of whom 114 were evaluable for clinical and microbiological response assessment: 56 received CP and 58 received CZ. About 50% (30 who received CP and 25 who received CZ) fulfilled the criteria of the sepsis syndrome. The treatment groups were comparable with respect to sex distribution, mean age, underlying diseases, treatment duration, APACHE II score, and type of infection. The most commonly cultured microorganisms were members of the family Enterobacteriaceae, Streptococcus pneumoniae, and Staphylococcus aureus. The causative microorganisms were eradicated from 92% (37 of 40) of patients with a microbiologically documented infection who underwent treatment with CP; they were eradicated from 86% (42 to 49) of patients who received CZ. The responses of only clinically documented infections in the CP group were 90% (27 of 30 patients); in the CZ group they were 87% (26 of 30 patients). When patients fulfilled the criteria of the sepsis syndrome (septic shock excluded), the causative microorganisms were eradicated from 89% (16 of 18) of CP-treated patients and 86% (12 of 14) of CZ-treated patients. None of these differences was statistically significant. Mortality was the same in both groups (four patients in each group) and was not attributable to the study medication. In conclusion, CP is at least as effective and as safe as CZ, as initial antimicrobial therapy for suspected serious bacterial infections in nonneutropenic patients with or without the sepsis syndrome. CP has the additional advantage in that it can be given twice daily, which may lead to a decrease in hospital costs.
PMCID: PMC284473  PMID: 8203833
5.  Aspirin does not improve early arterial patency after streptokinase treatment for acute myocardial infarction. 
British Heart Journal  1993;69(6):492-495.
OBJECTIVE--To investigate the hypothesis that the magnitude of the life saving effect of aspirin in the second international study of infarct survival (ISIS-2) trial cannot be explained solely by prevention of late reocclusion of the infarct related artery. The aim of this study was to discover whether or not aspirin in combination with streptokinase had an adjuvant thrombolytic effect. DESIGN--Aspirin (150 mg) or placebo was given at the start of streptokinase infusion to 200 patients seen within six hours of the start of prolonged ischaemic cardiac pain and ST segment elevation. All patients received active aspirin at three hours. Patency of the infarct related artery was assessed non-invasively by the normalised rise of creatine kinase activity at three hours after starting streptokinase in these 200 patients and in a further 52 patients who had already taken aspirin within one week of the start of infarction. MAIN OUTCOME MEASURE--Rise in creatine kinase activity from baseline to > or = 20% or < 20% of the peak rise of activity in blood taken at three hours after starting infusion of streptokinase. This correlates with patency or occlusion of the infarct related coronary artery at about 2.5 hours after starting streptokinase. RESULTS--Assessed in this way, patency of the infarct related artery was 60% in patients given aspirin, 63% in those given placebo, and 62% in patients who had already taken aspirin within one week of infarction. CONCLUSION--The magnitude of the life saving effect of aspirin remains unexplained. Further investigation is needed into the mechanism of action of antiplatelet treatment in relation to thrombolytic treatment.
PMCID: PMC1025158  PMID: 8343314
6.  Detection of parvovirus B19 in donated blood: a model system for screening by polymerase chain reaction. 
Journal of Clinical Microbiology  1993;31(2):323-328.
A highly sensitive and rapid method for routinely screening large numbers of donated blood units for parvovirus B19 by the polymerase chain reaction (PCR) was developed. Over a 3-month trial period in Edinburgh, B19 DNA was detected in 6 of 20,000 consecutive units of blood (0.03%), in concentrations ranging from 2.4 x 10(4) to 5 x 10(10) copies of viral DNA per ml. Seroconversion for B19-specific immunoglobulin M and immunoglobulin G and disappearance of circulating B19 DNA occurred in the interval between donation and recall in four of the five implicated donors who could be recalled. B19 DNA was detected in 18 of 27 separate batches of non-heat-treated factor VIII and IX concentrate manufactured from donated plasma unscreened for B19 DNA. Dry-heat treatment at 80 degrees C for 72 h reduced but did not always eliminate detectable B19 from factor VIII concentrates, consistent with recent observations that current methods for virus inactivation during blood product manufacture are insufficient to entirely eliminate B19 infectivity. The methods developed in this study for PCR screening could be applied routinely to prevent transfusion of B19 in blood and blood products and could play an important role in the prevention of iatrogenic transmission of infection. PCR screening could also be used for detection and exclusion of a range of other transmission-associated viruses for which current serological detection methods are only partially effective.
PMCID: PMC262759  PMID: 8432819
7.  Pharmacokinetics of cefepime in patients with respiratory tract infections. 
Antimicrobial Agents and Chemotherapy  1990;34(10):1885-1888.
The steady-state pharmacokinetics of cefepime were evaluated in 10 middle-aged and elderly patients with acute lower respiratory tract infections who were receiving 1 g intravenously every 12 h. One preinfusion and 15 postinfusion serum samples and total urine output were collected over one dosing interval between days 3 and 8 of therapy. Cefepime concentrations in serum over time exhibited a multicompartmental profile. Peak and trough concentrations in serum determined by a validated high-performance liquid chromatography method were 71.2 +/- 17.2 (mean +/- standard deviation) and 6.0 +/- 4.9 mg/liter, respectively. The steady-state volume of distribution was 0.22 +/- 0.05 liter/kg. Elimination half-lives ranged from 1.93 to 6.04 h (3.92 +/- 1.28 h), and total body clearances ranged from 36.9 to 102 ml/min per 1.73 m2 (73.0 +/- 19.7 ml/min per 1.73 m2). The disposition of cefepime at steady state in patients was comparable to previous observations in healthy elderly volunteers. The predictive performance of regression equations derived from single-dose studies in volunteers relating creatinine clearance with total body and renal clearances of cefepime exhibited slight biases (mean predictive errors, -9.7 and 2.1 ml/min per 1.73 m2, respectively) and similar precisions. Predicted and observed total body clearances (63.3 +/- 25.1 versus 73.0 +/- 19.7 ml/min per 1.73 m2, respectively) and renal clearances (51.3 +/- 24.4 versus 49.3 +/- 19.6 ml/min per 1.73 m2, respectively) were not significantly different. The pharmacokinetics of cefepime in infected patients appeared to be unaltered by illness, and the steady-state disposition of cefepime was predictable from data derived from single-dose studies in volunteers.
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PMCID: PMC171959  PMID: 2291655
8.  HLA-B27 associated cross-reactive marker on the cells of New Zealand patients with ankylosing spondylitis. 
Annals of the Rheumatic Diseases  1986;45(2):144-148.
We have previously shown that antibodies raised in rabbits to certain enteric bacteria will specifically lyse, in a 51Cr release assay, the peripheral blood lymphocytes (PBL) of 80% of HLA-B27 positive patients with ankylosing spondylitis (B27+ AS+) but not the PBL of HLA-B27 positive normal controls (B27+ AS-). Other laboratories have been unable to reproduce these findings. This study was designed to ascertain whether this lack of reproducibility was due to a peculiarity of our B27+ AS+ patients or to technical difficulties in the complement mediated 51Cr release assay. We have shown in this blind study that the PBL of 16 out of 18 B27+ AS+ patients from a New Zealand population were lysed by our antisera but none of the PBL of 20 B27+ AS- normal controls were lysed. The phenomenon of 'cross reactivity' between certain enteric bacteria and B27+ AS+ PBL is not confined to the Sydney AS population.
PMCID: PMC1001837  PMID: 3484937
9.  Clinical features of meningococcal arthritis: a report of four cases. 
Annals of the Rheumatic Diseases  1985;44(11):790-792.
Four patients with Neisseria meningitidis infection complicated by arthritis are described. Three patients had an acute polyarthritis which responded quickly to antimicrobial therapy. A fourth patient developed a prolonged arthritis which occurred after the initial infection had been successfully treated. Tenosynovitis occurred as a complication in one case. Attention is drawn to possible confusion with gonococcal infection, and postulated pathological mechanisms are discussed.
PMCID: PMC1001779  PMID: 3933440
10.  Identification and expression of a human cytomegalovirus glycoprotein with homology to the Epstein-Barr virus BXLF2 product, varicella-zoster virus gpIII, and herpes simplex virus type 1 glycoprotein H. 
Journal of Virology  1988;62(4):1416-1422.
An open reading frame with the characteristics of a glycoprotein-coding sequence was identified by nucleotide sequencing of human cytomegalovirus (HCMV) genomic DNA. The predicted amino acid sequence was homologous with glycoprotein H of herpes simplex virus type 1 and the homologous protein of Epstein-Barr virus (BXLF2 gene product) and varicella-zoster virus (gpIII). Recombinant vaccinia viruses that expressed this gene were constructed. A glycoprotein of approximately 86 kilodaltons was immunoprecipitated from cells infected with the recombinant viruses and from HCMV-infected cells with a monoclonal antibody that efficiently neutralized HCMV infectivity. In HCMV-infected MRC5 cells, this glycoprotein was present on nuclear and cytoplasmic membranes, but in recombinant vaccinia virus-infected cells it accumulated predominantly on the nuclear membrane.
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PMCID: PMC253155  PMID: 2831402
11.  Employment in ankylosing spondylitis. 
Annals of the Rheumatic Diseases  1984;43(4):604-606.
All patients with ankylosing spondylitis attending our rheumatology clinics were reviewed to assess the effect of their disease on employment. Back movement was measured in three planes, chest expansion determined, and peripheral joint involvement was noted to see whether these correlated with work capability. Sixty patients were reviewed (47 men, 13 women; mean disease duration 24.3 years). Nine were unemployed, but only four of these attributed this condition to ankylosing spondylitis. Although all four had severe neck, back, and hip involvement, this did not differentiate them from other patients who were fully employed. There was no relationship between disease duration and employment. The prospect for continued employment in ankylosing spondylitis is good even when the disease is long standing and severe.
PMCID: PMC1001418  PMID: 6476919
12.  Ethnic difference in the prevalence of systemic lupus erythematosus. 
Annals of the Rheumatic Diseases  1983;42(5):529-532.
A retrospective study of systemic lupus erythematosus (SLE) was carried out in Auckland, New Zealand, for the years 1975 to 1980 inclusive. One hundred and fifty-one patients were found of which 106 fulfilled the American Rheumatism Association criteria. There were 15 deaths. Age-adjusted prevalence rates per 100 000 were estimated for all cases at the end of 1980 as follows: white 14.6, Polynesian 50.63, and other 19.11. There was a preponderance of females in each ethnic group, average 87% of all cases. Age-adjustment mortality rates per million patient years were: white 2.5 and Polynesians 13.0. Survival curves for both ethnic groups were similar. The prevalence rate in New Zealand Polynesian is significantly higher than in white counterparts which confirms the observation that the disease is commoner in the pigmented races.
PMCID: PMC1001290  PMID: 6625702
13.  The behaviour, development, and health of the young child: implications for care. 
Children with recurrent physical illnesses such as infections of the ears and chest are more likely than average to have developmental and behavioural disorders as well. Specialist skills are needed for the assessment and management of these disorders; the belief that "the child will grow out of it" is rarely correct. Any reorganisation of the child health services should take account of the need for children with developmental and behavioural disorders to be treated within the community by doctors and other health workers with the appropriate skills.
PMCID: PMC1548054  PMID: 6190531
14.  Search for viruses in rheumatoid macrophage-rich synovial cell populations. 
Annals of the Rheumatic Diseases  1980;39(2):159-163.
The adherent cells remaining after short-term culture of synovial fluid and synovial membrane cells from rheumatoid and non-rheumatoid patients were examined for the presence of a productive virus infection and for various viral antigens. Labelling was carried out with 3H-thymidine and 3H-uridine followed by sucrose density gradient centrifugation of the culture supernatant. Only in 1 case was there incorporation of 3H-uridine into material of density 1 . 21 g/cm3. Viral antigens were tested for by indirect immunofluorescence with antisera to rubella virus, the retroviruses RD-114 and simian sarcoma associated virus, early adenovirus type 2 antigens, late adenovirus type 2 antigens, SV-40 T antigen, and in 1 case measles virus. No cell showed immunofluorescence with any antiserum except the early adenovirus type 2 antiserum, which stained the cytoplasm of about half the synovial cell cultures, some from rheumatoid and some from non-rheumatoid patients.
PMCID: PMC1000502  PMID: 6992720
15.  Viruses and lymphocytes in rheumatoid arthritis. II. Examination of lymphocytes and sera from patients with rheumatoid arthritis for evidence of retrovirus infection. 
Annals of the Rheumatic Diseases  1979;38(6):514-525.
The possible involvement of retroviruses in the aetiology of rheumatoid arthritis (RA) was investigated. Retrovirus antigens were not expressed on rheumatoid synovial and peripheral blood lymphocytes as judged by membrane immunofluorescence, radioimmunoassay, and complement-mediated cytotoxicity. The specific antiretroviral (anti-RD-144 and anti-SSAV) sera used in this study were produced in rabbits immunised with viral antigens grown in a homologous system (rabbit cells and medium supplemented with normal rabbit serum), avoiding non-specific immunofluorescence previously detected with donated antiretroviral sera. Immune complexes lodged in the rheumatoid synovial membranes did not contain, and other cells within the membranes did not express, retroviral antigens. Antibodies cross-reacting with primate retrovirus antigens were sought in sera from patients with 'autoimmune' diseases by means of solid phase radioimmunoassay. There were no retrovirus antibodies in the 3 groups of patients studied, that is, those with rheumatoid arthritis, systemic lupus erythematosus, and with non-RA conditions. Absorption of rheumatoid factor did not alter this conclusion. These results give little support to the hypothesis that activation of endogenous human retroviruses or an infection with horizontally transmitted retroviruses is associated with the rheumatoid process.
PMCID: PMC1000411  PMID: 395909
16.  Viruses and lymphocytes in rheumatoid arthritis. I. Studies on cultured rheumatoid lymphocytes. 
Annals of the Rheumatic Diseases  1979;38(6):507-513.
Synovial fluid lymphocytes from patients with rheumatoid arthritis have been examined for evidence of a productive infection with retroviruses by electron microscopy, labelling with 3H-uredine, growth in soft agar, and culturing in conditioned medium. No such viruses were detected. In addition, the synovial lymphocytes were activated before fusion and cocultivation with several cell lines which have proved permissive for primate retroviruses. Monitoring these cultures subsequently by reverse transcriptase assay, labelling with 3H-uridine, and membrane immunofluorescence gave no indication that retroviruses were present.
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PMCID: PMC1000410  PMID: 539843
17.  Lack of association of cytomegalovirus with adenocarcinoma of the colon. 
Gut  1982;23(1):21-30.
Tumor specimens from patients with adenocarcinoma of the colon or rectum were examined for the presence of cytomegalovirus (CMV), and specimens of normal mucosa from the same patients were studied in parallel. Frozen sections of 14 specimens were made and the presence of CMV mRNA assayed by in situ hybridisation using 3H-labelled CMV-DNA as a probe. Nine of these sections were also tested for cytomegalovirus antigens by immunofluorescence. No viral nucleic acids or antigens were detected. In addition to these direct approaches, the specimens were disaggregated and 19 were successfully cultured in various media over several months without yielding virus on any occasion. Areas containing epithelial cells were found in some cultures, foci of bipolar cells in others, while, in several, fibroblastic cells predominated. To ensure that any virus-containing cells were not lost by this method, the disaggregated tumour and normal intestinal cells were directly co-cultivated and also fused with human embryo lung cells, which are permissive for cytomegalovirus replication. The resulting cultures were examined over two to three months for the presence of cytomegalovirus, and in no instance was virus found, despite attempted induction by iododeoxyuridine. Two fusion cultures became contaminated with cytomegalovirus, strain AD-169, which was being handled in the laboratory at the same time. The strain was identified by the pattern of viral DNA fragments produced by restriction endonuclease cleavage. Thus the accidental passage of virus in the heterokaryons did not alter its DNA and would further indicate the absence of any cytomegalovirus genomes in the adenocarcinoma cells.
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PMCID: PMC1419583  PMID: 6276266
18.  Rheumatoid polyarthritis after rubella. 
Annals of the Rheumatic Diseases  1978;37(3):266-272.
A 21-year-old woman developed persistent polyarthritis indistinguishable from rheumatoid arthritis after rubella. The arthritis persisted for approximately 30 months and was associated with high levels of antibody to rubella virus and with rheumatoid factor. The antibody titres declined pari passu with clinical improvement which progressed to complete resolution. Fractionation of serial serum specimens showed a substantial and persistent IgM antibody response to rubella virus. Rubella antigen was not demonstrated in the synovial exudate.
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PMCID: PMC1000220  PMID: 686860
19.  Use of the child health clinic. 
Archives of Disease in Childhood  1981;56(6):440-445.
Attendance at child health clinics in two areas of London, north Westminster and south Camden, is described. Routine examinations were attended by 97% of children although such visits accounted for only one-third of attendances. There were more non-routine visits than have been reported in most other studies--about 14 visits in Westminster and 12 in Camden during the first year. Over half the mothers sought advice on a wide variety of medical, developmental, and behavioural problems.
PMCID: PMC1627470  PMID: 7259274
22.  Rubella virus and rheumatoid arthritis. 
A collection of synovial fibroblasts from 19 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthrosis or other non-RA disease has been examined for rubella virus antigens by immunofluorescence and radioimmunoassay with negative results. Eluates of synovial membrane prepared under conditions likely to dissociate antigen-antibody complexes have shown no rubella antibody. A serological survey of RA patients and those with other forms of arthritis has shown no differences in the frequency or levels of rubella haemagglutination-inhibiting antibody. These results provide little support for various hypotheses that a persistent infection with rubella virus underlies or initiates the rheumatoid process.
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PMCID: PMC1006622  PMID: 320944
23.  The conveyance of patients to and from hospital, 1720--1850. 
Medical History  1978;22(4):397-407.
PMCID: PMC1082329  PMID: 362087
25.  Health needs of preschool children. 
Archives of Disease in Childhood  1976;51(11):848-852.
An epidemiological study of disease in a geographically identified population of 250 children is reported. 22% had not seen their general practitioner (GP) at all in the past year, while 20% had seen him four times or more. The vast majority of these visits were because of an infective illness; and developmental and behavioural problems were rarely presented to GPs. 53% of children had not been to hospital since birth, but 11% had been at least four times. Respiratory infections and middle ear disease were the commonest illness reported, and nearly 3% had an infected or discharging ear at the time of examination. 15% of 3 year olds had speech and language problems. 18% of children over 2 years were thought by the examiners to have a behavioural problem, half being assessed as mild, the remainder as moderate or severe.
PMCID: PMC1546081  PMID: 1008590

Results 1-25 (27)