Biomedical subjects
Publications and source records attributed to J Dowling.
Six cases of malignant prolactinoma have been reported; an additional two cases are presented here and the literature is reviewed. Diagnosis rests upon evidence of metastasis rather than histological criteria per se. Cases have arisen from known adenomas, particularly the invasive type. Bromocriptine is a useful palliative. The features and treatment of malignant prolactinoma are discussed.
Legionella micdadei is a human pathogen which survives within leukocytes. To determine how this organism escapes intracellular destruction, we examined its effect on human neutrophil activity. Neutrophils were allowed to ingest L. micdadei prior to evaluation of functional activity. Compared with control cells which did not ingest organisms, cells ingesting L. micdadei showed significantly depressed production of superoxide anion (24.5 +/- 9.0 nmol/10(6) cells per 15 min versus 6.9 +/- 3.2 nmol/10(6) cells per 15 min, respectively; P = 0.002), chemotaxis (43.9 +/- 0.8 mm versus 0.9 +/- 1.3 mm of directed migration, respectively; P = 0.001) and bactericidal activity against Staphylococcus aureus (97.9% versus 37.6% of ingested organisms killed, respectively; P = 0.001). Similar degrees of inhibition could not be demonstrated when either Staphylococcus aureus or Escherichia coli was ingested by cells prior to evaluation. Inhibition of neutrophil function did not occur when phagocytosis of L. micdadei was prevented. However, inhibition occurred with heat-killed as well as with viable organisms. The inhibition of neutrophil function by ingested L. micdadei may help explain the bacterium's ability to survive intracellularly and may begin to explain the pathogenesis of this disease.
The association of anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis and glomerular immune complexes is common and probably arises from a number of mechanisms. In the series, glomerular immune complexes were identified in 6 of 17 patients who initially presented with anti-GBM disease. In four cases, glomerular immune complexes were noted in renal biopsies obtained at clinical presentation; in the other two, they were first demonstrated seven and 28 months after presentation, when circulating anti-GBM antibody levels were undetectable. Circulating immune complexes were detected in only two of six patients, either 28 months before or 17 months after the demonstration of the glomerular membranous lesion. The association of glomerular immune complexes and anti-GBM disease may be coincidental with immunologically-unrelated immune complexes localizing in the GBM for physico-chemical reasons; or the presence of glomerular-bound anti-GBM antibodies may predispose to the deposition of molecules with particular affinity for these antibodies. One patient with glomerular immune complexes used heroin, which may be associated with immune complex formation and the development of glomerulonephritis; and one patient was subsequently thought to have systemic lupus erythematosus (SLE). An antecedent infection was found in two of the four patients who had glomerular complexes at presentation, but in only three of 13 with uncomplicated anti-GBM disease. Three of 6 patients with superimposed glomerular complexes had a history of exposure to organic solvents before the onset of disease, while none in the group with anti-GBM disease alone had.
We have synthesized three peptides corresponding to putative antigenic regions in the immunogenic domain, hinge region, and carboxy-terminus of the protein. A rabbit immunized with a peptide derived from the hinge region of the receptor produced an antiserum which showed 50% displacement with 20 pg peptide at a final serum dilution of 1:35,000. When the antiserum was immunopurified and applied to sections of intact rat and human kidney it stained cells lining segments corresponding to distal tubule, connecting piece, and initial cortical collecting duct, consistent with the known sites of mineralocorticoid action. In both human (formaldehyde-fixed) and rat (Bouin's solution) there was ample evidence for both nuclear and cytoplasmic staining. The thymus, in which previously we have found [3H]aldosterone binding to be below detection limits, showed little or no staining. Western blot analyses demonstrated that the polyclonal antibody recognized an epitope of the expected molecular size. The availability of antibodies to the mineralocorticoid receptor should, thus, facilitate investigation of the steroid specificity-conferring mechanism which allows mineralocorticoids, but not glucocorticoids, access to the nonselective receptor in the kidney.
In a prospective study of patients with haematemesis and melaena, there were 22 admissions of patients with bleeding stomal ulceration, representing 2.5% of total admissions to the Unit. In 16 patients the bleeding was from superficial stomal lesions. These lesions, endoscopically and histologically, resembled alkaline reflux gastritis, a recently defined cause of postgastrectomy bile vomiting. Five patients presented with chronic ulceration following inadequate gastric surgery. One patient was admitted on two occasions. Nine patients received more than five units of blood and came to operation for continued bleeding. In seven of the surgical cases, the bleeding was from superficial stomal lesions. Our experience suggests that truncal vagotomy is necessary to control the bleeding in these patients. One patient presented with superficial stomal ulceration and carcinomatous change. This patient died. It is important to subject these lesions to biopsy, and biopsy with extension of a previous gastrectomy is indicated to control bleeding, and to exclude malignancy.
Lymphomatoid granulomatosis is a multi-system disorder of high mortality and characterised by angiocentric and angiodestructive lymphoreticular proliferative and granulomatous change. A case is described of this disease occurring in a renal transplant patient. The patient underwent a rapid remission of the disease after a course of combined cytotoxic therapy and remains free of disease three years after treatment. This case is the second described renal transplant patient to develop the disease and the first to be successfully treated. It is likely that the disease originated as a consequence of immunosuppression similar to the development of lymphomas in allograft recipients.
Since the recent introduction of the Roche Oxi/Ferm Tube to the UK two identification schemes have been developed by the manufacturer for use with the kit. We evaluated the success of these two schemes in identifying 222 predominantly culture collection strains belonging to 45 taxa of non-fermenters and nine taxa of oxidase-positive fermenters. The strains were chosen to represent all the taxa included in the two identification schemes developed by the manufacturer and we have therefore been able to assess the overall success of identification by the two schemes. Since, however, our choice of strains does not reflect their incidence in clinical material, our identification rates are not necessarily those that might be obtained in a routine clinical laboratory. The most advanced identification scheme so far developed for the Oxi/Ferm Tube (CCIS System 1977-1432) allowed 62% of the 222 strains to be correctly identified although a disturbing feature was that more of the strains that were not correctly identified were incorrectly identified (24%) rather than not identified (14%); these figures represent an improvement over the earlier identification scheme (CCIS System 1976-621-74346) for which the corresponding figures were 56%, 32%, and 12%. CCIS System 1977-1432 seems likely to give a better performance in a routine clinical laboratory than in this study since for those taxa which, we would judge from the material sent to us for identification, are most commonly seen in a routine laboratory (Acinetobacter calcoaceticus, A. lwoffii, Pseudomonas aeruginosa, P. fluorescens, P. maltophilia, P. pseudoalcaligenes, and P. putida) 89% were correctly identified, none remained unidentified, and 11% were incorrectly identified. Thirty strains, each of a different taxon, were tested in triplicate to assess the reproducibility of reactions in the Oxi/Ferm Tube.
Lipoplysaccharide (endotoxin) from E. coli cells produced lethal effects in guinea-pigs. Endotoxin caused no visible dermal change in normal animals, but produced skin reactions characterized by specific Arthus-type (Type III immune hypersensitivity) vascular inflammation in immunized animals. It is concluded that Arthus allergic reactions were evoked by endotoxin, however, endotoxin lethal toxicity appears independent of this process.
The case reported in this paper appears to be the first example of spontaneous subarachnoid haemorrhage complicating an acoustic tumour. The only comparable case is one of a pontocerebellar angle tumour, but its histological nature is unstated. The excellent response to surgical management has been gratifying, and the patient has remained well over an extended period of surveillance.
Nephropathy with proteinuria is an occasional complication of gold therapy for rheumatoid arthritis and is considered to be due to an immune hypersensitivity reaction. Three patients are described in whom the structural changes typical of gold nephropathy were demonstrated by electron microscopy of renal biopsies. There was early membranous glomerular nephropathy with multiple sub-epithelial deposits of immune complexes. In one case these were shown by immunofluorescence to contain IgG and complement. Proximal tubules contained characteristic dense granular intracytoplasmic gold inclusions, best demonstrated by electron microscopy of unstained sections.