Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids.

Hybridomas the produce anti-DNA autoantibodies were prepared from spleen cells of unimmunized MRL/1 mice, a strain that spontaneously develops severe systemic lupus erythematous (SLE). Reactivities of these monoclonal antibodies with a wide range of polynucleotides prompted tests of their reactions with phospholipids which, like polynucleotides, contain diester-linked phosphate groups in their backbones. In competitive radioimmunoassays, cardiolipin, phosphatidic acid, and phosphatidyl glycerol blocked the binding of these hybridoma antibodies to denatured DNA. These phospholipids also specifically inhibited the reaction between a hybridoma antibody and a site-specific anti-idiotypic antibody. The antinuclear reaction of one of these antibodies was specifically inhibited by cardiolipin. This same antibody prolonged the activated partial thromboplastin time in a manner characteristic of a lupus anticoagulant, presumably by binding to phospholipid in the test system. The polyspecific reactivity of a single molecular species of lupus autoantibody suggests that some of the diverse serological abnormalities of SLE may be a result of the binding of certain autoantibodies to a phosphodiester-containing epitope that is present in diverse biological molecules.

Adrenocortical hyperactivity with disseminated malacoplakia.

A case is described of an ectopic ACTH syndrome associated with malacoplakia.

Acute urinary retention attributable to sacral herpes zoster.

Acute urinary retention in women is uncommon. A 63 year old woman presented with suprapubic pain, a palpable bladder, and multiple grouped vesicles on the right buttock. Catheterisation showed a residual of 2000 ml. A case is reported of acute urinary retention secondary to herpes zoster infection of the sacral nerves (S2-4).

Perioperative nursing research. Part VII: Postoperative care.

The implications for further research will be determined by the changes in surgery and perioperative nursing itself. Things are changing. The development of biliary lithotripsy and more flexible laser angioplasty, to name but two, will reduce the potential for traditional complications of surgery. Bleeding and infection will diminish with less invasive procedures. Similarly, the postoperative course of surgical patients will be assisted by earlier signs detected by pulse oximeters, more accurate assessments of neurological status, and even intraoperative management of acute myocardial infarction. The role of the perioperative nurse will be by no means diminished. In fact, it will expand.

Parathyroid hormone as a marker for metabolic bone disease of prematurity.

OBJECTIVE: To compare parathyroid hormone to alkaline phosphatase as a serologic marker for metabolic bone disease (MBD) in preterm infants. STUDY DESIGN: An 18-month prospective observational study in neonates with birth weight < 1250 g. Simultaneous serum parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium (Ca) and phosphorus (P) were measured at scheduled intervals during hospitalization. At 6 weeks of age, MBD was evaluated using knee radiographs. Comparisons were analyzed using multivariate logistic regression, receiver operating characteristic (ROC) curves, χ² and Student t-test. RESULT: Fourty-nine infants were included in the study: 7 with severe and 42 with mild MBD. Using ROC curves, at 660 U l⁻¹ ALP had a sensitivity of 29% and specificity of 93% for severe MBD, while a cutoff point of 180 pg ml⁻¹ gave PTH a sensitivity of 71% and specificity of 88%. Infants with severe bone disease had a lower birth weight, 21-day serum P, an increased use of glucocorticoids and caffeine, and more likely to have major neonatal morbidities. CONCLUSION: PTH is an early marker with better sensitivity than ALP in screening for MBD. At 3 weeks chronologic age, a PTH level > 180 mg dl⁻¹ or a P level <4.6 pg ml⁻¹ yielded a sensitivity of 100% and specificity of 94% for severe MBD [corrected].

Crohn's disease presenting as left gluteal abscess.

Although abscesses and fistulae are common complications of Crohn's disease, the gluteal area is a rare site for abscess formation. The abscess results from extension of pus through the fascial plains of the pelvis and through the greater sciatic foramen into the gluteal area. This is the first reported left gluteal abscess due to Crohn's disease as pus extends across the midline to the left side. The clinical picture can be misleading and diagnosing the source of infection may be difficult. Incision of this abscess without identifying the source of infection will result in enterocutaneous fistula. Ultrasound guided aspiration of the abscess as well as treatment of metabolic deficiencies and septicaemia before definitive surgical treatment of the bowel disease will reduce the morbidity and mortality of this rare complication. The clinical picture, management of this complication and review of the literature are discussed.

Is anyone speaking my language?

This paper describes an on-going three-phase action research project undertaken by members of the Norwich Community Trust speech and language therapy adult services team. With the support of the Clinical Audit department the project was set up in order to: 1) investigate the characteristics, needs and aspirations of the population of dysphasic people in the community; 2) examine how dysphasic people and their families perceive the speech and language therapy service; 3) implement specific changes to the speech and language therapy service to dysphasic people and their families. These changes are based on proposals developed through a working partnership between the speech and language therapy department and dysphasic people and their families.

Prostatectomy in a district hospital.

In order to monitor the safety and efficacy of a new service for transurethral prostatectomy, an audit was performed, prospectively, over a period of 7.25 years. Of 304 prostatectomies performed, 91% were by transurethral prostatectomy. The proportion of patients with retention was 52%, 16% were uraemic and the incidence of carcinoma of the prostate was 21%. The operative mortality rate was 1.0%. An outline of the treatment policy and the data on complications and revision operations are presented. Comparisons are made with the experience of teaching centres and other district hospitals. Transurethral prostatectomy can be performed safely in the district general hospital and is a service which is essential to the smooth running of the surgical department.

Faecal bile acid concentration of patients with carcinoma or increased risk of carcinoma in the large bowel.

Faecal 3-hydroxy bile acids were assayed enzymatically in patients with carcinoma, or at increased risk of developing carcinoma of the large bowel. No rise in bile acid concentration was demonstrated in patients with ulcerative colitis, previously resected adenoma, or resected carcinoma. Patients with carcinoma, before treatment, had faecal bile acid concentrations similar to control values, and surgery did not affect the mean level. These findings cast doubt on the importance of the 3-hydroxy bile acid concentration in the faeces in the pathogenesis of large bowel cancer.

Human monoclonal antibodies to phenolic glycolipid-I derived from patients with leprosy, and production of specific anti-idiotypes.

Human monoclonal antibodies (mAb) were produced by hybridomas derived from fusion of the GM4672 lymphoblastoid cell line and peripheral blood mononuclear cells from leprosy patients. Hybridoma supernatants were screened for immunoglobulin (Ig) secretion, binding to Mycobacterium leprae, phenolic glycolipid-I (Phen GL-I), the unique M. leprae glycolipid and single-stranded(ss)DNA by ELISA. On the basis of direct-binding ELISAs, two IgMk mAb (PR4 and TH3) were selected for characterization. PR4 and TH3 bound to M. leprae, Phen GL-I and ssDNA; PR4 also bound to M. avium and M. kansasii and TH3 to M. kansasii. Inhibition assays demonstrated that these antibodies did not bind to the terminal disaccharide of Phen GL-I. In addition, both PR4 and TH3 bound to several autoantigens: ssDNA, double-stranded(ds)DNA and poly(ADP-ribose) but not RNA. PR4 and TH3 were used for preparation of rabbit anti-idiotype antisera. Inhibition studies demonstrated that the affinity purified rabbit anti-idiotype antisera were specific for their respective idiotype and that both Phen GL-I and ssDNA inhibited binding of idiotype to its anti-idiotype. PR4, but not TH3, was found to be similar but not identical to the 16/6 idiotype originally identified on a human monoclonal anti-DNA antibody derived from a patient with systemic lupus erythematosus (SLE).

Assessment of the immune deficit in leprosy patients and the effect of recombinant IL-2 in vitro.

Although the mechanism of immunologic unresponsiveness in lepromatous leprosy remains unknown, it has been shown that interleukin-2 (IL-2) production is defective in these patients. Peripheral blood mononuclear cells (PBMC) were isolated from treated (less than 16 months) and untreated leprosy patients as well as household contacts; age, sex, ethnically matched control subjects; and laboratory staff. PBMC were cultured for 6 days with sonicated Mycobacterium leprae (1-10 micrograms/ml), Dharmendra lepromin (1:10), or phenolic glycolipid-I (PGL-I) (0.05-5.0 micrograms/ml) in medium supplemented with various concentrations of recombinant IL-2 (rIL-2) or cultured for 3 days with one of the three mycobacterial antigens in the presence of concanavalin A (ConA). TT/BT patients and household control subjects had a robust response to M. leprae and lepromin, but were unresponsive to PGL-I delivered in liposomes. PBMC from LL patients did not respond to any of the three antigen preparations. rIL-2 induced proliferation of PBMC both in leprosy patients and control subjects regardless of the presence or absence of the three leprosy antigen preparations. This antigen nonspecific augmentation of proliferation by the wide range of doses of rIL-2 employed makes difficult the interpretation of the enhanced thymidine incorporation noted when rIL-2 is added in the presence of antigen to cultures of lymphocytes from LL patients. Our studies are at variance with reports that leprosy antigens, specifically PGL-I, induce immunological suppression, in that mycobacterial antigens did not cause significant suppression of the ConA-induced proliferations of PBMC from patients.

Expression of a common idiotype PR4 in the sera of patients with leprosy.

The sera of 187 patients from across the leprosy spectrum were screened for the expression of the PR4 idiotype, which was first identified on a human hybridoma-derived monoclonal antibody from a patient with leprosy and found to react with the Mycobacterium leprae phenolic glycolipid and a variety of polynucleotides. Sixty per cent (51 out of 85) of patients with lepromatous leprosy (LL), 66% (33 out of 49) with borderline lepromatous (BL) disease, 47% (14 out of 30) with borderline tuberculoid (BT) leprosy, and 56% (13 out of 23) of tuberculoid (TT) patients were found to have significantly elevated titres of the PR4 idiotype in their sera compared with endemic controls, irrespective of the presence or absence of endemic malaria. Sera from 52 patients with tuberculosis were also screened as a control for mycobacterial infection. The PR4 idiotype was significantly elevated in 37% (19 out of 52) of these patients. No correlation between idiotype and serum immunoglobulins IgG and IgM was found, indicating that the concentrations of idiotype levels in sera were not merely a reflection of changes in serum immunoglobulin levels. It is hypothesized that the expression of the PR4 idiotype is due to certain germline genes preferentially expressed rather than being the result of polyclonal B cell activation.

Polyspecificity of human monoclonal antibodies reactive with Mycobacterium leprae, mitochondria, ssDNA, cytoskeletal proteins, and the acetylcholine receptor.

The origin of autoantibodies against ubiquitous autoantigens (e.g., single-stranded (SS) DNA, cytoskeletal proteins, mitochondria) is obscure. Patients with lepromatous leprosy have many such autoantibodies in their serum. In order to study the polyspecificities of human autoantibodies expressed during infection with Mycobacterium leprae we prepared human monoclonal antibodies derived from the fusion of peripheral blood lymphocytes of a patient with lepromatous leprosy to the human lymphoblastoid line GM 4672. Hybridomas were tested for binding to a DNAse-treated sonicate of M. leprae and a panel of autoantigens. Of the primary (uncloned) cultures, 14% bound ssDNA, 35% bound M. leprae, 11% bound both M. leprae and ssDNA, and 16% bound to mitochondria. Several also bound to the acetylcholine receptor of Torpedo marmorata. Monoclonal antibodies derived from separate primary cultures revealed similar cross-reactions between several autoantigens and M. leprae. In addition, one antibody was identified which bound to mitochondria and the acetylcholine receptor, and which was recognized by an anti-idiotypic antibody which bears the "internal image" of the acetylcholine receptor. These results suggest that antigenic mimicry may play a role in eliciting autoantibody expression from the immune repertoire.