Wegener's Granuloma. A Series of 265 British Cases Seen Between 1975 and 1985. A Report by a Sub-committee of the British Thoracic Society Research Committee

In order to describe the British experience of Wegener's granuiomatosisHospital Activity Analysis was used to collect cases diagnosedin England, Wales and Scotland between 1975 and 1985. Wherepossible clinical details, histological material and chest radiographswere obtained. Two hundred and sixty five patients were consideredto have Wegener's granuiomatosis. In 109 a single pathologistconfirmed the diagnosis by finding both granulomas and vasculitisin biopsy material. The diagnosis was made on clinical groundsor clinical grounds together with histological diagnosis inthe local hospital in 156 patients. Wegener's granuiomatosiswas confined to the lung or upper respiratory tract in 22 percent of patients and renal disease occurred in 58 per cent.Laboratory tests showed a pattern of mild anaemia, polymorphleucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia,with no specific pattern of changes. Histological confirmation was most frequently obtained by examinationof nasal biopsy specimens, but multiple biopsies were oftenrequired. Renal biopsies showed focal proliferative glomerulonephritisbut granulomatous glomerulonephritis was uncommon. Of availablechest radiographs 61 per cent were abnormal, large opacitiesbeing most common. Small irregular opacities were found lessoften and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients receivedno drug therapy. This large series illustrates that even withoutspecific treatment, patients with Wegener's granuiomatosis cansurvive for several years and with modern treatment survivalfor more than a decade is possible. Conclusions about the effectivenessof the various therapies cannot be drawn from this restrospectivestudy. Renal failure and disseminated vasculities were the commonestcauses of death; death was considered to result from complicationsof treatment with cytotoxic drugs or prednisolone in 6 per centof patients.     

Demonstration by the monoclonal antibody-specific immobilization of erythrocyte antigens assay that a new red cell antigen belongs to the Kell blood group system

BACKGROUND: The Kell blood group system comprises 21 antigens residing on a red cell membrane glycoprotein of apparent M(r) 93,000. STUDY DESIGN AND METHODS: Serologic techniques were used to identify a new red cell antigen. The monoclonal antibody-specific immobilization of erythrocyte antigens (MAIEA) assay was used to identify the red cell membrane component carrying that antigen. RESULTS: A new high-frequency red cell antigen was identified and provisionally named RAZ. RAZ is absent from K.o red cells and from red cells treated with 2-amino- ethylisothiouronium bromide and is expressed weakly on McLeod phenotype cells. It differs from all other Kell system antigens, and no depression of other Kell system antigens on RAZ+ red cells was noticed. The RAZ antigen was shown by the MAIEA assay to be located on the Kell glycoprotein. CONCLUSION: RAZ is a new high-frequency antigen located on the Kell glycoprotein. The MAIEA assay is a very effective method of demonstrating the membrane structure carrying a red cell antigen.     

Acoustic monitoring (RFM) of total hip arthroplasty results of a cadaver study

Introduction

At present there are no reliable non-traumatic and non-invasive methods to analyse the healing process and loosening status after total hip replacement. Therefore early as well as late loosening of prosthesis and interface component problems are difficult to be found or diagnosed at any time.

Methods

In a cadaver study the potential application of Resonance Frequency Monitoring (RFM) will be evaluated as a non-invasive and non-traumatic method to monitor loosening and interface problems in hip replacement. In a 65 year old female cadaver different stability scenarios for a total hip replacement (shaft, head/modular head and cup, ESKA, Luebeck, Germany) are simulated in cemented and cement less prosthesis and then analysed with RFM. The types of stability vary from secure/press-fit to interface-shaft disruption.

Results

The RFM shows in cemented as well as cement less prosthesis significant intra-individual differences in the spectral measurements with a high dynamic (20 dB difference corresponding to the factor 100 (10000%)), regarding the simulated status of stability in the prosthesis system.

Conclusion

The results of the study demonstrate RFM as a highly sensitive non-invasive and non-traumatic method to support the application of RFM as a hip prosthesis monitoring procedure. The data obtained shows the possibility to use RFM for osteointegration surveillance and early detection of interface problems, but will require further evaluation in clinical and experimental studies.     

Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Cardiac CT and MRI guide surgery in impending left ventricular rupture after acute myocardial infarction

We report the case of a 67 year-old patient who presented with worsening chest pain and shortness of breath, four days post acute myocardial infarction. Contrast enhanced computed tomography of the chest ruled out a pulmonary embolus but revealed an unexpected small subepicardial aneurysm (SEA) in the lateral left ventricular wall which was confirmed on cardiac magnetic resonance imaging. Intraoperative palpation of the left lateral wall was guided by the cardiac MRI and CT findings and confirmed the presence of focally thinned and weakened myocardium, covered by epicardial fat. An aneurysmorrhaphy was subsequently performed in addition to coronary bypass surgery and a mitral valve repair. The patient was discharged home on post operative day eight in good condition and is feeling well 2 years after surgery.     

Evaluation of clinical and laboratory correlates of sickle leg ulcers

The exact mechanism for the occurrence of sickle leg ulcers (SLUs) has not been fully explained, although, popular opinion supports a multifactorial etio‐pathogenetic process. Leg ulceration in sickle cell is a chronic and debilitating condition which is difficult to treat and may worsen the psychosocial impact of this illness. This study aims to evaluate the laboratory and clinical correlates of SLUs. One hundred sixty‐seven patients who had been diagnosed with sickle cell anemia (homozygous S) had their steady‐state hemoglobin concentration (Hb), hematocrit, white cell count, platelet count, serum bilirubin, and aspartate transaminase (AST) as well as frequency of crisis per annum evaluated with respect to their relationship to the occurrence of leg ulcers. They were aged 6–53 years (mean age 24.3 years), and prevalence of leg ulcer was found to be 2.75 per 1000 (2.54 per 1000 in females and 2.83 per 1000 in males). The independent sample t‐test showed a significant difference in the serum AST levels in those with SLU (p = 0.029), though a positive correlation did not exist. Other predictors of disease severity found to have positive relationship with each other were the AST and total serum bilirubin 0.207 (p = 0.012); Hb and age 0.130 (p = 0.035); Hb and white cell count ?0.159 (p = 0.010), white cell count and age ?0.113 (p = 0.018). SLUs do not occur in patients with severe disease in sickle cell. The clinical and laboratory indicators of severe sickle cell disease do not correlate positively with the occurrence of SLU. Serum AST may have a relationship with leg ulceration in these patients. Environmental factors most likely play a major part in the etiopathogenesis of leg ulcer and this may require further studies in different sociocultural settings.     

Role of cyclooxygenase-2 in the angiogenesis of colorectal cancer

BACKGROUND: Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of prostaglandins. It exists in two isoforms: COX-1 which is constitutively expressed and COX-2 which is an inducible form activated by a variety of cytokines during inflammation. DISCUSSION: Interest in this enzyme arose in the early 1990s when, following epidemiological studies, aspirin (which is a COX inhibitor) was found to reduce the risk of colorectal cancer. Since then various studies to decipher the mechanisms by which COX reduces the development of colorectal cancer have been undertaken. One of the mechanisms being studied is its role in the angiogenesis of colorectal cancer. Angiogenesis of its own has been well established as a key factor in the development of tumours. Agents that specifically inhibit COX-2 are now in clinical development and have been licensed to be used in patients with familial adenomatosis polyposis. CONCLUSION: What needs to be determined is whether the antiangiogenic effects of COX-2 inhibitors can be used in the prevention and/or treatment of colorectal cancer and its metastases.