Diffuse interlobular septal thickening in a coal miner.

Diffuse interlobular septal thickening (DIST) is an abnormality seen on high-resolution CT (HRCT) scanning of the thorax. While DIST may be present to variable extents in a number of lung conditions, it is uncommon as a predominant finding except in a few entities. This report features an ex-coal miner, thought to have coal workers' pneumoconiosis (CWP), in whom the HRCT scan showed no evidence of CWP and instead showed DIST. The patient's condition progressed incessantly towards death from severe secondary pulmonary hypertension. The case links fatal pulmonary hypertension to DIST, a pattern not previously described in coal workers.

Analysis of an IL-10 polymorphism in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disorder of the lung parenchyma. We have demonstrated changes in IL-10 protein production by alveolar macrophages (AMs) from patients with IPF, which we hypothesise could be because of an IL-10 gene polymorphism. We have screened the coding sequence and 3' untranslated region of IL-10 for polymorphisms using single-standard conformational polymorphism analysis. A novel polymorphism was identified resulting in a G to A substitution of +43 nucleotides from the start codon changing glycine to arginine at amino acid 15 of the signal peptide sequence. We have introduced the signal peptide mutation into the IL-10 gene and compared secretion of the mutant and wild-type forms after transient transfection of COS-7 cells. Our studies showed that the signal peptide mutation did not have a significant effect on secretion at 24 h post-transfection (P=0.4529 by Mann-Whitney test). However, by 48 h there are significantly lower levels of mutant IL-10 (P=0.0515). There were no differences in the level of cell-associated IL-10 at either 24 or 48 h (P=0.9296 and 0.4268). We suggest that the mutation could affect the efficiency of protein translocation and signal peptide cleavage resulting in lower levels of IL-10 protein secretion.

Murine gammaherpes virus as a cofactor in the development of pulmonary fibrosis in bleomycin resistant mice.

Studies of human tissue have suggested an association between productive Epstein Barr virus and idiopathic pulmonary fibrosis (IPF). However, a pathogenic role for the virus has not been established. This study was undertaken to develop an animal model, which would explore the association between viral infection and pulmonary fibrosis. BALB/c mice (n=30), resistant to bleomycin, were primed with murine gammaherpesvirus 68 and then given intraperitoneal bleomycin. The mice were sacrificed at 28 days after bleomycin and their lungs assessed histologically and biochemically. Lung pathology was scored 0-3 for fibrotic and inflammatory change. BALB/c mice given virus and bleomycin showed more lung fibrosis (median score 2.2) compared to those given bleomycin alone (median 0), virus alone (median 0.2) or phosphate-buffered saline (PBS) control (median 0). Similarly mice given both virus and bleomycin showed more lung inflammation (median score 1.9) compared to those given bleomycin (median 0.5), virus (median 0.8), or PBS control (median 0.2). There was a significant difference in collagen content between the bleomycin and virus group (mean 1.86 mg) compared to the belomycin alone group (mean 1.52 mg). These results suggest that virus alone does not result in pulmonary fibrosis but that replicating virus in the presence of an exogenous injury may promote the development of pulmonary fibrosis.

A prospective study of a quantitative PCR ELISA assay for the diagnosis of CMV pneumonia in lung and heart-transplant recipients.

BACKGROUND: Qualitative polymerase chain reaction (PCR) for the identification of cytomegalovirus (CMV) infection has a low predictive value for the identification of CMV pneumonia. This study prospectively evaluated the application of a quantitative PCR Enzyme-Linked Immuno-Sorbent Assay (ELISA) assay in 9 lung- and 18 heart-transplant recipients who did not receive ganciclovir prophylaxis. METHODS: DNA was collected from peripheral blood polymorphonuclear leucocytes (PMNL) posttransplantation. Oligonucleotide primers for the glycoprotein B gene (149 bp) were used in a PCR ELISA assay using an internal standard for quantitation. CMV disease was defined as histological evidence of end organ damage. RESULTS: The median level CMV genome equivalents in patients with CMV disease was 2665/2 x 10(5) PMNL (range 1,200 to 61,606) compared to 100 x 10(5) PMNL (range 20 to 855) with infection but no CMV disease (p = 0.036). All patients with CMV disease had genome equivalents levels of >1200/2 x 10(5) PMNL. A cut-off level of 1,200 PMNL had a positive predictive value for CMV disease of 100% and a negative predictive value of 100%. The first detection of levels of CMV genome equivalents above a level of 1200/2 x 10(5) PMNL was at a median of 58 days (range 47 to 147) posttransplant. CONCLUSIONS: Quantitative PCR assays for the diagnosis of CMV infection may predict patients at risk of CMV disease and thereby direct preemptive treatment to high-risk patients.

Normal coronary angiograms: financial victory from the brink of clinical defeat?

OBJECTIVE: To examine the hypothesis that, in patients undergoing coronary angiography for suspected ischaemic heart disease, a normal angiographic result is associated with a fall in consumption of health care resources following the angiogram. DESIGN: Retrospective cost-benefit analysis comparing the 12 month periods before and after coronary angiography. SETTING: Tertiary cardiac referral centre. SUBJECTS: 69 consecutive patients investigated in the financial year 1991-92 whose angiograms were normal. MAIN OUTCOME MEASURES: Drug and hospital admission costs in the 12 month periods before and after angiography; urgent and elective consultations with general practitioner in that time. RESULTS: The mean cost of care per patient in the year before investigation was 656.89 pounds. A highly significant fall in all indices of resource consumption was observed in the year following investigation, the mean resulting difference in the cost of care being 35.15 pounds per month. The cost of coronary angiography would, if this fall were maintained, be recouped in a mean time of 18 months. CONCLUSIONS: Patients suspected on clinical grounds to have coronary atherosclerosis who are found at angiography to have normal coronary arteries are heavy consumers of health care resources. Early investigation for these patients is safe and has beneficial resource consequences in the medium term.

Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)

The cardiovascular actions of the magnesium ion at pharmacological concentrations include coronary and systemic vasodilatation, platelet inhibition, and antiarrhythmic effects. Magnesium has also been reported to protect myocardial tissue in experimental models of ischaemia and reperfusion. Several small clinical trials in suspected acute myocardial infarction have suggested that early mortality can be reduced by intravenous infusion of magnesium salts in the acute phase, but none has been of sufficient size to be conclusive. We therefore conducted a randomised, double blind, placebo controlled study in 2316 patients with suspected acute myocardial infarction who received either intravenous magnesium sulphate (8 mmol over 5 min followed by 65 mmol over 24 h) or physiological saline. The primary outcome measure was 28-day mortality, which was ascertained in 99.3% of patients. The groups were well balanced for prognostic factors. By intention-to-treat analysis mortality from all causes was 7.8% in the magnesium group and 10.3% in the placebo group (2p = 0.04), a relative reduction of 24% (95% confidence interval 1-43%). Within the coronary care unit the incidence of left ventricular failure was reduced by 25% (7-39%) in the magnesium group (2p = 0.009). There was no significant difference between the groups in the incidence of heart block or the use of antiarrhythmic drugs, direct-current cardioversion, or temporary pacing. Myocardial infarction was confirmed in 65% of each group, with closely similar rises in cardiac enzymes. The side-effects of magnesium treatment were transient flushing, related to speed of injection of the loading dose, and an increased incidence of sinus bradycardia (2p = 0.02). Exploratory subgroup analyses of 28-day mortality did not indicate any effect modification by thrombolysis or aspirin, or by previous treatment with beta blockers, calcium antagonists, or diuretics. Intravenous magnesium sulphate is a simple, safe, and widely applicable treatment. Its efficacy in reducing early mortality of myocardial infarction is comparable to, but independent of, that of thrombolytic or antiplatelet therapy.

An audit of patients attending a general medical follow-up clinic.

Of the 418 consecutive patients attending a general medical clinic for follow-up, 113 (27%) had appointments in another medical clinic for the same or a related problem; 98 of them (87%) were attending a clinic in a different hospital. The reasons for multiple clinic attendance were routine follow-up after hospital admission in 55 (49%), referrals from general practitioners to more than one clinic in 33 (30%), and cross-referrals from the 'parent' medical firm in 19 (17%). In six patients no clear reason for multiple attendances could be identified. More than half (55%) were over 65 years old, 45% lived more than five miles from the hospital, and 78% depended on ambulance, friends, or relatives for transport. We suggest that follow-up attendances at outpatient clinics should be stringently reviewed and should only be maintained if a clear reason can be identified. This would not only ensure a more effective service overall but would also save patients and relatives from inconvenience.

Terminal-deoxynucleotidyl transferase (TdT): serial observations on patients with leukemia.

Terminal-deoxynucleotidyl transferase (TdT) bone marrow determinations were performed on 67 patients with leukemia using the indirect immunofluorescence technique. A total of 103 smears were evaluated on 32 patients with acute lymphoblastic leukemia. With some exceptions, TdT levels were elevated at onset, declined during induction except in resistant cases, decreased during remission on chemotherapy, showed slight elevation during remission off chemotherapy, and rose during relapse in those cases previously positive. The most important finding was that patients in remission may have elevated TdT levels. Those were usually less than 10%. A total of 124 bone marrow smears were evaluated on 29 patients with acute myeloid leukemia. In general, values in all categories were below 1%, with a few elevated between 1% to 10%. Six patients with chronic myelogenous leukemia in blast crisis had 13 bone marrow smears evaluated. Five were in myeloblastic crisis and had values of less than 1%; 1 was lymphoblastic which had 50% positive cells at onset. In our experience, TdT determinations are of value in lymphoblastic leukemia in diagnosis, in predicting response to therapy, and in detecting early relapse.

Acute myeloid leukemia with hand-mirror cells.

A retrospective analysis of 37 cases of acute myeloid leukemia (AML) seen during five years was undertaken to evaluate the presence in the bone marrow of hand-mirror cells (HMCs). Three cases with greater than 5% HMC were investigated by light and electron microscopy, cytochemistry, levels of terminal-deoxy-nucleotidyl-transferase, study of histologic aspects of bone marrow clot and biopsy specimens, and bone marrow immune complexes for numerous viruses. The findings supported the myeloid nature of the HMC; however, immune complexes associated with the baboon endogenous virus was absent, a finding that has been observed in all cases of acute lymphoblastic leukemia (ALL) with HMCs so studied. In light of this finding, it was suggested that HMCs are produced in ALL and AML by different mechanisms. In addition, the patients with AML-HMC did not survive longer than those without HMCs in the bone marrow. Further studies in larger groups are needed to clarify the phenomenon of HMC formation in AML and its relation to survival.

Coronary arterial disease in systemic lupus erythematosus; quantification of degrees of narrowing in 22 necropsy patients (21 women) aged 16 to 37 years.

The degrees of cross-sectional area luminal narrowing by atherosclerotic plaques of each 5 mm long segment of each of the four major (right, left main, left anterior descending and left circumflex) epicardial coronary arteries in 22 necropsy patients (age 16 to 37 years, 21 women) with systemic lupus erythematosus (SLE) was determined, and the findings were compared to those in 13 control subjects. Of 623 coronary segments (5 mm long) in the patients with SLE, 80 (13 percent) were narrowed 76 to 100 percent (controls = 0 of 431 segments); 125 (20 percent), 51 to 75 percent (controls = 6 percent); 273 (44 percent), 26 to 50 percent (controls = 31 percent). Of the 22 patients with SLE, 10 had one or more of the four major coronary arteries narrowed 76 to 100 percent in cross-sectional area, and 12 patients had lesser degrees of narrowing similar to that in the 13 control subjects. The 10 patients with SLE and severe coronary narrowing compared to the 12 patients with SLE and no severe (greater than 75 percent) coronary narrowing had significantly higher (1) mean values of total serum cholesterol (382 versus 290 mg/dl), (2) mean systolic/diastolic systemic arterial pressures (175/119 versus 151/93 mm Hg), (3) frequencies of mitral valvular disease (seven of 10 patients versus none of 12 patients) and (4) frequencies of pericardial adhesions (seven of 10 patients versus three of 12 patients).

An epidemiological study of strains of Shigella sonnei from two related outbreaks.

During the winter of 1967-8 Sonne dysentery affected neighbouring North London primary schools. This was not simply due to cross-infection between the two schools, for two different, unusual strains of Sh. sonnei were distinguished. One was a novel kanamycin-resistant colicine type 7 strain, and as far as we know this was the first school outbreak due to such a strain to be documented. The other strain was kanamycin-sensitive and of colicine type 0 with a rare specific requirement for aspartic acid. There was some evidence to suggest that the kanamycin-resistant strain was more infective for adults and possibly more pathogenic than the kanamycin-sensitive.Studies on the transfer of drug resistance and of colicinogeny revealed that the factor determining colicine type 7 was carried on a transmissible plasmid, a new observation. Various drug resistances were also transmissible experimentally, and some were spontaneously unstable. Non-transferable ampicillin-resistance in the colicine type 7 strain and aspartic acid dependence in the colicine type 0 strain enabled all but one of the isolates to be classified into two distinct lines. No common ancestor was found and it was concluded that although occurring together they must have arisen from separate sources.