Ageing and genetic control of immune responsiveness

Ageing is associated with a progressive decline of immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena [1,2]. Many studies have been focussed on the mechanisms of the immunologic features of ageing. Alterations in cellular components of the immune system rather than in the extracellular milieu seem to account for most of the variations of immune competence in ageing [3].     

The safety of anakinra in high-risk patients with active rheumatoid arthritis: six-month observations of patients with comorbid conditions

OBJECTIVE: To determine in a placebo-controlled, double-blind trial the safety profile of daily anakinra (Kineret) use in patients with active rheumatoid arthritis (RA) and concurrent comorbid conditions. METHODS: In 169 centers in 9 countries, 1,414 patients with active RA were randomly assigned to receive either anakinra (100 mg) or placebo treatment (4:1 anakinra-to-placebo allocation ratio), with study drug administered by daily subcutaneous injection for 6 months. The current post hoc analysis assessed baseline comorbid conditions, and patients were considered at high risk for the occurrence of adverse events if they had a history of at least one of the following: cardiovascular event, pulmonary event, central nervous system-related event, infection, diabetes, malignancy, or renal impairment. Within each treatment group (anakinra or placebo), incidence rates were summarized for serious adverse events, infectious events, and serious infectious events in high-risk patients and compared with these incidence rates in patients without comorbid conditions. RESULTS: The majority of patients in the trial had one or more comorbid conditions. In these high-risk patients, there were no differences in the incidence of serious adverse events or infectious events between treatment groups. The incidence of serious infectious events with anakinra use was similar between high-risk patients (2.5%) and the entire study population (2.1%) and was not attributable to any single comorbidity. CONCLUSION: Results of the analysis of adverse events in patients with active RA and coexisting comorbidities suggest that the favorable safety profile of anakinra is maintained in a high-risk patient population.     

Platelet alpha2-adrenoreceptors in obsessive-compulsive disorder

The need for new therapeutic targets in obsessive-compulsive disorder (OCD) prompted us to investigate the putative involvement of the norepinephrine system by means of platelet alpha(2)-adrenoreceptors in a group of 20 OCD patients and healthy control subjects, matched for sex and age. Platelet membranes were prepared according to standard protocols, and the alpha(2)-adrenoreceptors were measured by means of the specific binding of [(3)H]rauwolscine, a highly selective antagonist for this receptor subtype. The results, which showed no difference between patients and controls in the binding parameters of [(3)H]rauwolscine, suggest that the role of alpha(2)-adrenoreceptors, as reflected by the platelet model, is quite limited in OCD and may, perhaps, be restricted purely to some symptoms or dimensions such as motricity, as suggested by the higher density of alpha(2)-adrenoreceptors found in patients concomitantly affected by motor tics.     

Low Total Cholesterol and Increased Risk of Dying: Are Low Levels Clinical Warning Signs in the Elderly? Results from the Italian Longitudinal Study on Aging

OBJECTIVES: To analyze the relationship between serum total cholesterol (TC) and all-cause mortality, taking into account various potential confounders. DESIGN: Population-based prospective cohort study. SETTING: Older Italians residing in the general community. PARTICIPANTS: Four thousand five hundred twenty-one men and women aged 65-84. MEASUREMENTS: Vital status data were available for 1992-95. The hazard ratios of dying for subjects in the second, third, and fourth quartiles compared with the first quartile of TC were computed using Cox proportional hazards, adjusting for lifestyle factors, anthropomorphic and biochemical measures, preexisting medical conditions, and frailty indicators. RESULTS: Blood samples were obtained from 3,295 (73%) of the participants, of whom 399 died during almost 3 years of follow-up. Low TC was associated with a higher risk of death. Those with TC in the second, third, and fourth quartiles (TC>189 mg/dL or 4.90 mmol/L) had lower hazard ratios (HRs) of death than subjects in the first quartile (0.57, 95% confidence interval (CI) = 0.38-0.87; 0.56, 95% CI = 0.36-0.88; and 0.53, 95% CI = 0.33-0.84, respectively). Few subjects taking lipid-lowering drugs (LLDs) were in the lowest quartile of cholesterol, suggesting that these individuals have low TC values for reasons other than LLD use. CONCLUSION: Subjects with low TC levels (<189 mg/dL) are at higher risk of dying even when many related factors have been taken into account. Although more data are needed to clarify the association between TC and all-cause mortality in older individuals, physicians may want to regard very low levels of cholesterol as potential warning signs of occult disease or as signals of rapidly declining health.     

Prolylhydroxylase and procollagen type III in long-term survivors of acute lymphoblastic leukemia (ALL): a biochemical approach to HCV-related liver disease

BACKGROUND: We examined two proteins, prolylhydroxylase (hPH) and procollagen type III (PIIIP), as possible non-invasive HCV-related markers of liver disease. The purpose of this study was to assess whether the measurement of these proteins could serve to monitor HCV related liver damage in acute lymphoblastic leukaemia (ALL) patients. PROCEDURE: A total of 34 ALL patients, 24 HCV-seropositive and 10 HCV-seronegative, who had had increased transaminase values (ALT) for almost 6 months were studied. Serum hPH concentrations were determined by an immuno-enzymatic assay kit. PIIIP was assayed by the radioimmunoassay method. RESULTS: Both hPH and PIIIP were increased in ALL patients with chronic hepatitis C. Serum hPH levels were significantly elevated in those with chronic hepatitis C with either normal or high transaminases when compared to those who never were HCV seropositive. The sensitivity and specificity of these protein measurements to evaluate hepatic fibrosis were not supported by histologic confirmation because only 6 out of 12 patients with chronic hepatitis had a liver biopsy. CONCLUSIONS: Our study suggests that PIIIP and hPH values are significantly higher in ALL patients with chronic HCV with either normal or high transaminases. This might suggest that the liver damage is more marked in patients with chronic hepatitis and that the liver damage is related to the HCV rather than chemotherapy. Future studies correlating histologic findings with the serum biochemical markers are required to establish the sensitivity and specificity of hPH and PIIIP in predicting hepatic fibrosis and to confirm this association.     

Skin and eye: uncommon sites of distant metastasis from tongue base squamous cell carcinoma

The frequency of non-lymphatic distant metastases from primary head and neck squamous cell carcinoma (SCC) appears to be higher than previously presumed. The general conditions of the affected patients, who usually also present with locoregional recurrences, are so impaired as to limit the use of available methods for diagnosing the distant spread of head and neck SCC. The incidence reported in autopsy studies is approximately three to four times higher than that in clinical studies. Lung metastases from head and neck SCC are most common, followed by metastases to bone and liver. Metastases to the skin are unusual. Secondary ocular localizations of head and neck SCC are exceedingly rare. We report the first case of synchronous intraocular (involving the choroid and vitreous body) and cutaneous metastases from a recurrent tongue base SCC in a 64-year-old woman who had undergone radiotherapy, bilateral neck dissection and chemotherapy. Cytological evaluation of vitreous aspirate and histological diagnosis of the skin lesion were performed < 1 month before the patient's death. Skin metastases occur in 1-4% of patients with diagnosed head and neck SCC and are usually associated with advanced or recurrent disease. To the best of our knowledge, fewer than 10 cases of ocular metastases from head and neck SCC have been reported. The average survival time after diagnosis of ocular or skin metastases from head and neck SCC is 7 months. Treatment for eye and skin metastases is palliative and rarely alters patient outcome.     

Ceramic model for temporal bone exercises--an alternative for human temporal bones?

BACKGROUND: The complexity of the temporal bone anatomy makes it necessary to train in a model before starting middle ear surgery. The classical object are human cadaver temporal bones, but these are not always available for different reasons. Alternatively in cooperation between the department of otolaryngology, head and neck surgery of the University of Jena and the 3di company Jena, Germany, a calcium sulfate based model was developed. METHODS: During a temporal bone course at the Bugando Medical Centre, Mwanza, Tanzania, these ceramic temporal bone specimens were used for training. Because of the lack of drills, the specimens were worked on in chisel and carving technique. All participants were beginners in ear surgery. Classical procedures in mastoid surgery were performed: Exposing of sigmoid sinus, facial nerve, labyrinth, dura, jugular bulb and internal carotid artery. RESULTS: The temporal bone models were very useful for these exercises. Good exposure was possible for the dura, the facial nerve and the major blood vessels. The possibility of exposing tinier structures like the labyrinth was still insufficient. Nevertheless the understanding of the 3-dimensional anatomy of the temporal bone using the ceramic model was excellent. The relationship of all important anatomical structures could be taught intensively. CONCLUSIONS: Particularly for beginners or in cases where human temporal bones are not available the calcium sulfate based temporal bone is an alternative training model for mastoid and middle ear surgery.     

Quality assurance in diagnostic radiology: practical outcomes

Over the last four years, our Health Physics Department has implemented a quality control programme focusing on the performance of the diagnostic X-ray machines in use at our hospital. The results of the tests performed (X-ray and light field alignment, tube voltage reproducibility and accuracy, ) were used to compare the 1999 and 2002 findings by means of the chi squared and Fischer statistical tests. The comparison has demonstrated that the decrease in the number of non-conformities, also emerging from a simple comparative analysis on the experimental data, was statistically significant with a p<0.05 for all of the X-ray machines examined. This finding confirms that our quality control programme had positive effects on the overall performance of the hospital diagnostic X-ray equipment, and appears to justify the resources employed for its implementation.