DNA-DR typing shows HLA-DRw11 RFLPs are increased in frequency in both progressive systemic sclerosis and CREST variants of scleroderma

DNA-DR typing of patients with both Progressive Systemic Sclerosis and CREST variants of Scleroderma has shown an increase in frequency of DRw11 RFLPs. The frequency of DQw7 was also increased in the patient groups, but this was due to linkage disequilibrium with DRw11.     

C1 inhibitor functional deficiency in systemic lupus erythematosus (SLE).

C1 inhibitor (C1-inh) was assayed in eight SLE patients presenting with consistently low levels of intact C4. C1-inh antigenic levels were normal in all patients; however, the function of the C1-inh tested against C1s and C1r was variable and outside the normal functional range in seven of the eight patients. The molecular weight of patients' C1-inh protein was 105 kD, corresponding to the size of the intact molecule. The C1-inh gene was analysed in all patients. Restriction fragments generated with TaqI, PstI and HgiAI gave no indication of a major C1-inh gene rearrangement. Direct genomic sequencing of exon VIII revealed three polymorphic point mutations, but there were no changes from the normal gene in or around the reactive-centre residue of C1-inh. Furthermore, we found no evidence for a C1-inh autoantibody in patients which could affect normal C1-inh function in vitro. These results indicate that the etiology of C1-inh dysfunction in SLE is heterogeneous and distinct from that reported in either hereditary or acquired angioedema.     

Myocardial Infarction in Wegener's Granulomatosis

A case is described of a 28-year-old man who presented with a picture of classical Wegener's granulomatosis; and who, in the absence of fulminating renal or respiratory disease died from myocardial infarction. Other reports of cardiac involvement are discussed and compared with the picture presented by this patient.     

Differences between C4A and C4B in the handling of immune complexes: the enhancement of CR1 binding is more important than the inhibition of immunoprecipitation.

There are two isotypes of C4--C4A and C4B--, encoded within the major histocompatibility complex with quite different properties. In this study we have compared purified C4A and C4B with regard to their ability to prevent immune complex precipitation and to enhance the binding of both preformed and nascent immune complexes to the receptor CR1 on red cells. C4A was modestly more effective than C4B at inhibiting immunoprecipitation, particularly in antibody excess. In the CR1 binding assay C4A was markedly more effective than C4B in enhancing binding to CR1. This difference was seen with both preformed and nascent immune complexes at equivalence and antibody excess. Thus the major differences between C4A and C4B in regard to immune complex handling is at the level of CR1 binding. Given the strong association of C4A* QO alleles with immune complex-mediated diseases like systemic lupus erythematosus, these findings have important pathogenetic implications.     

Symptomatic abdominal bronchogenic cyst mimicking acute ischemic heart disease

A 57-year-old female patient presented with a symptomatic abdominal bronchogenic cyst that was associated with ECG changes. The patient's clinical presentation with chest pain, ST and T wave changes, and rate-related bundle branch block initially suggested a myocardial infarction. The ECG reverted to normal after the cyst was removed. The physiologic origins of these observations are unknown.     

Helper and suppressor activities of lymphocyte subsets on antithyroglobulin production in vitro

We studied the regulatory activities of T cells on specific antithyroglobulin (anti-Tg) and nonspecific immunoglobulin secretion in cultures of peripheral blood lymphocytes (PBL) of five patients with autoimmune thyroid diseases and high levels of serum anti-Tg. PBL were separated into a non-T population, including B-cells and monocytes, and a T-cell population by rosetting with sheep red cells. T-Cells were further separated into T helper (Th) and T suppressor (Ts) subsets by a panning technique using the monoclonal antibodies anti-Leu 3a and anti-Leu 2a, respectively. The three sets of cells, i.e. B, Th, and Ts, from patients and from normal individuals were cocultured in various combinations and stimulated with the polyclonal stimulant pokeweed mitogen. A sensitive plaque assay was used to enumerate cells producing anti-Tg and protein A-binding immunoglobulins. The PBL of both patients and normal individuals had Tg-specific suppressor cells. Ts-cells from patients in syngeneic or allogeneic combinations with B- and Th-cells at a ratio of 1:1:1 suppressed the pokeweed mitogen-induced anti-Tg response to 41 +/- 8% (+/-SE) and 50 +/- 20% of the control value, respectively, while Ts from normal individuals suppressed the response to 7 +/- 3% of the control value. The suppressive effect of the Ts-cells from patients and normal individuals on nonspecific immunoglobulin secretion was similar (reduced to 10-15% of control). Thus, there appeared to be a deficiency in Tg-specific suppressor activity in PBL of patients. On the other hand, Th-cells from patients (syngeneic or allogeneic) cocultured with patient B-cells produced a greater anti-Tg response than Th-cells from normal individuals. The helper activities of Th-cells of patients and normal individuals on nonspecific immunoglobulin secretion were similar. Thus, there appeared to be an increase in Tg-specific helper activity in PBL of patients.     

The pharmacist as a nutrition educator? An assessment of nutritional knowledge and undergraduate training of community pharmacists

A nutrition knowledge questionnaire was sent to 240 randomly selected community pharmacists in the UK, with a response rate of 31% (n –75). The questions were designed to assess knowledge of nutrition, knowledge of current dietary recommendations and the practical application of this knowledge. In addition, some questions were asked about the educational background of the pharmacist. The overall mean score on the nutrition section was 67.5% (range 35–90%) which was better than possibly anticipated when considering their lack of nutritional education. The survey of nutrition content of courses within pharmacy schools indicated that the teaching of nutrition is limited. Only two schools reported separate courses in nutrition, elsewhere the subject was incorporated into other courses with an average time allocation of only 2 h. However, as a result of the questionnaire some of the pharmacists made comments suggesting concern about the inadequacy of their knowledge of, and undergraduate and postqualification training in, nutrition.     

Controversies in the antiphospholipid syndrome and stroke

Many clinicians providing care and advice to patients with antiphospholipid syndrome (APS), where the principal clinical manifestation is stroke, do so in the setting of an evidence base of mixed quality. Indeed, systematic studies have not particularly helped the practising clinician as they have been characterised by variable criteria used to select subjects, making it impossible to extrapolate to typical clinic patients. This has left us with a number of key questions, each of which attracts controversy in terms of patient management. In this review, these are posed as a series of questions with the answer, or lack of one, considered after each question. The review draws attention to the important questions that require answers for current primary and secondary prevention, as well as treatment of APS and stroke, and suggests a series of studies that are needed to clarify these issues.