Immunoglobin synthesis by fresh biopsy cells and established cell lines from Burkitt''s lymphoma

(1) Freshly dispersed cells from four Burkitt's lymphoma biopsies, and three `lymphoblast' cell lines (OB2, OB3 and OB6) derived from the tumour were tested for capacity to synthesize immunoglobulins in vitro.

Using labelled amino acid incorporation, electrophoretic, radio-immunoelectrophoretic and ultracentrifugation techniques, it was possible to demonstrate the release of labelled proteins with antigenic characteristics of immunoglobulins by all four biopsy samples, and the two cell lines tested by these techniques. Newly synthesized labelled proteins were demonstrable in the culture medium within 1 hour of incubation.

In a separate series of experiments, absorption and immunodiffusion techniques were used in the characterization of proteins synthesized by two cell lines (OB2 and OB3) growing as healthy continuous cultures.

(2) Freshly isolated cells from Burkitt's lymphoma are capable of immunoglobulin synthesis in vitro. Cells from all four fresh biopsy materials produced IgG. One cell line (OB2) produced IgG and type-κ light chains, while OB6 cell line produced IgA. Immunoglobulin synthesis was not detected in OB3 cell line by immunodiffusion technique.

(3) Cells from each biopsy specimen or cell line produced not more than one type of immunoglobulin, although there was a wide variation in the sedimentation coefficient of the protein molecules synthesized by one (OB6) and presumably all other cell lines.

     

Value of whole-cell antigen extracts for serologic detection of Helicobacter pylori.

Whole-cell protein extracts of Helicobacter pylori strains were evaluated by enzyme-linked immunosorbent assay to detect immunoglobulin G antibody against H. pylori in 113 patients with upper gastrointestinal complaints. These antigen preparations were of value for detecting infection by H. pylori in patients with high antibody titers (> or = 12,800), whereas for patients with lower titers, the results were inconclusive.     

Use of H2-receptor antagonists in patients with dyspepsia and heartburn: a cost comparison.

OBJECTIVE: Under the Pharmaceutical Benefits Scheme, the use of H2-receptor antagonists (H2A) in the treatment of dyspepsia and heartburn is only subsidised when there is a proven diagnosis of ulcer. This study compared the costs of this Australian practice with a simulation of British practice, which allows unrestricted prescribing of subsidised H2A. DESIGN: Patients with heartburn and/or dyspepsia were prospectively randomised to either a "British" group treated freely at the discretion of their general practitioner without necessarily being investigated or an "Australian" group where use of H2A was allowed only after gastroscopy or a barium meal had demonstrated a peptic ulcer or ulcerative oesophagitis. The patients were followed up for six months and all direct and indirect costs were recorded. SETTING: Forty-nine Sydney general practitioners recruited primary care patients for the study. PATIENTS: Any patient with heartburn or dyspepsia was considered for recruitment; 139 patients entered the study and 137 completed it. MAIN OUTCOME MEASURES: The outcome measures were the costs of general practitioner consultations, specialist consultations, radiology and gastroscopy, other tests, H2A, other medications, personal costs, and total cost per patient. RESULTS: The cumulative total cost per patient at the end of the study was equivalent in the "Australian" ($392) and "British" ($406) groups. A higher initial cost per patient of H2A in the "British" group was offset by a rapid decrease in the proportion that continued to use H2A and by the cost of specialist consultations and investigations in the "Australian" group. CONCLUSION: Over a six-month period the cost of early investigation of heartburn and dyspepsia was equivalent to the cost of a therapeutic trial of H2A.     

Chromosome aberrations in coeliac and non-coeliac enteropathies

The frequency of chromosomal aberrations in peripheral blood lymphocytes was assessed in three groups of children: untreated coeliac disease (n = 20); non-coeliac disease enteropathies (n = 15); controls (n = 15). The mean frequency of aberrant cells and the total number of aberrations per 100 metaphases was increased in the coeliac disease group compared with controls by factors of 5 and 6, respectively (p < 0.01 for both). Aberrant cells and total aberrations were similarly increased in the non-coeliac disease enteropathy group by a factor of 3.7 in each case (p < 0.05). However, the frequency of aberrations in the two enteropathy groups was not significantly different. Children with coeliac disease, similar to affected adults, have evidence of increased chromosomal instability. However, similarly increased chromosomal aberrations are seen in children with non-coeliac disease enteropathies, indicating that the abnormality is not specific for coeliac disease.     

Does a single plasma phenylalanine predict quality of control in phenylketonuria?

A 1993 MRC working group on phenylketonuria suggested standardising blood phenylalanine measurements by taking blood samples at the same time each day. Since it is not known how representative of a 24 hour period a single phenylalanine concentration is, the aim of this study was to investigate the 24 hour variability of plasma phenylalanine in well controlled children with phenylketonuria. Sixteen subjects, 12 girls and four boys aged 1 to 18 years, had hourly venous blood samples collected for 13 hours between 09.00 and 21.00 on one day. Serial skin puncture blood specimens were then collected at 24.00, 03.00, and 06.00 within the same 24 hour period. All food and drink was weighed. The median variation in plasma phenylalanine concentration was 155 mumol/l/day, with a minimum of 80 and a maximum of 280. The highest concentration occurred in the morning between 6.00 and 9.00 in 63% of subjects; the lowest occurred between midday and midnight in 94%. Concentrations < 100 mumol/l occurred in 46% of children below 11 years, three having concentrations < 30 mumol/l for two, six, and seven hours respectively. Three of five subjects had concentrations above the MRC guidelines for 24% of the period studied. Except in two subjects, the blood concentrations did not rise in response to phenylalanine consumption. However, the greater the quantity of protein substitute taken between waking and the 16.00 specimen, the larger the decrease in daytime phenylalanine concentration (r = -0.7030) (p < 0.005). There is therefore wide variability in phenylalanine concentrations in a 24 hour period in children with phenylketonuria which is not reflected in a single observation. Further study is needed to investigate the effects of timing of protein substitute on the stability of phenylalanine concentrations.     

Effect of age, Helicobacter pylori infection, and gastritis with atrophy on serum gastrin and gastric acid secretion in healthy men.

Gastric acid secretion has been considered to decline with increasing age but this view is being re-evaluated as the importance of Helicobacter pylori infection emerges. This study aimed to determine the effect of age, H pylori, and gastritis with atrophy on the serum gastrin concentration, gastric secretory volumes, and acid output in healthy, asymptomatic men. Young men (mean (SD) age 22.9 (0.6) years; n = 22) were compared with old men (72.9 (1.2) years; n = 28) in respect of basal serum gastrin and basal, sham fed, pentagastrin stimulated maximal and peak acid secretion. Antral, corpus, and fundal biopsy specimens were taken for histology and H pylori status (histology, culture, and rapid urease test). H pylori associated gastritis was present in three of 22 young (13.6%) and 16 of 28 old (57.1%) men. Gastritis with atrophy was present in 11 old subjects, 10 of whom were H pylori positive. These subjects had higher mean (SD) serum gastrin concentrations than old subjects without atrophy and young subjects (61.8 (9.2); 40.0 (2.9); 36.8 (2.3) pmol/l respectively; p < 0.001). H pylori infected subjects had higher gastrin values than uninfected subjects, overall (55.3 (5.9); 36.0 (1.8) pmol/l; p < 0.001) and in subjects without atrophy (45.3 (4.2); 36.0 (1.8) pmol/l; p < 0.03). In subjects without H pylori infection, gastrin values did not differ with age (old 37.1 (1.7); young 35.4 (2.1) pmol/l). The maximal gastric secretory volume was lower in old subjects with atrophy. Acid output (mmol/h) in subjects with atrophy was lower than in subjects with no atrophy (basal: 3.0(1.1); 5.1(0.7); p=NS; sham led: 5.4 (1.4); 9.3 (0.8); p<0.02; maximal: 18.9 (4.0); 31.4(1.8); p<0.002; peak: 25.1(5.3); 43.4(2.7); p<0.003). However, acid secretion in old subjects without atrophy was not different to that in young subjects, irrespective of H pylori status. These results did not differ when acid output was expressed as mmol/h/kg lean body mass or mmol/h/kg fat free body weight. Using multiple linear regression analysis, gastritis with atrophy was the only factor that had an independent negative effect on acid secretion. In healthy men without atrophy, gastric acid secretion is preserved with ageing and is independent of H pylori status. Atrophy, which is closely related to H pylori infection, is associated with a decline in acid secretion. Increased basal serum gastrin is related to both atrophy and H pylori infection but not to ageing per se.     

Admission inflammatory markers and isolation of a causative organism in patients with spontaneous spinal infection

Introduction

The purpose of this study was to investigate the significance of the inflammatory markers on admission in the isolation of a causative pathogen in patients with spinal infection. Spinal infection is treated frequently at spinal units and can encompass a broad range of clinical entities. Its diagnosis is often delayed because of the difficulty of identifying the responsible pathogen.

Methods

Patients with spinal infection treated in our institution over a period of eight years were identified and their notes studied retrospectively. Admission C-reactive protein (CRP), white cell count (WCC) as well as co-morbidities and mode of pathogen identification were recorded. Overall, 96 patients were included in the study.

Results

The CRP levels on admission were correlated significantly with the overall potential for isolation of a pathogen (p<0.0001) and positive biopsy cultures (p=0.0016). Admission WCC levels were associated significantly with the overall potential for isolation of a pathogen (p=0.0003) and positive biopsy cultures (p=0.0023). Both CRP and WCC levels were significantly negatively correlated with the duration of the preceding symptoms (p=0.0003 and p<0.0001 respectively). Delay in presentation was significantly negatively correlated with organism isolation (p=0.0001). Multivariate analyses identified the delay in presentation as the strongest independent variable for organism isolation (p=0.014) in cases of spontaneous spinal infection when compared with the admission CRP level (p=0.031) and WCC (p=0.056).

Conclusions

In spontaneous spinal infection, delay in presentation is the strongest independent variable for organism isolation. High inflammatory marker levels on admission are a useful prognostic marker for the overall potential of isolating a causative organism either by blood cultures or by biopsy in patients with negative blood cultures. Furthermore, the admission inflammatory marker levels allow for treating surgeons to counsel their patients of the likelihood of achieving a positive microbiological yield from biopsy.