Hypercalcemia secondary to leprosy

Despite the high prevalence of leprosy in undeveloped countries, hypercalcemia secondary to leprosy is rare. One of most important mechanisms responsible for this disorder seems to be high serum concentrations of 1,25-dihydroxyvitamin D produced extrarenally by the granulomatous tissue. Serum levels of parathyroid hormone-related protein (PTHrP) have never been analyzed in this disorder. We report here a case of hypercalcemia in a patient with leprosy. Serum levels of 1,25-dihydroxyvitamin D were normal in spite of low levels of 25-dihydroxyvitamin D and acute renal failure. Suppressed serum levels of parathyroid hormone and PTHrP were also remarkable. In this case, PTHrP seems not to play an important role in the pathogenesis of hypercalcemia. Our data indicate that this disorder may be due, at least in part, to abnormal calcitriol overproduction by granulomatous tissue. Further investigations of the prevalence and pathogenesis of this type of hypercalcemia are needed.     

Language-association cortex asymmetry in autism and specific language impairment

Language deficits are among the core impairments of autism. We previously reported asymmetry reversal of frontal language cortex in boys with autism. Specific language impairment (SLI) and autism share similar language deficits and may share genetic links. This study evaluated asymmetry of frontal language cortex in a new, independent sample of right-handed boys, including a new sample of boys with autism and a group of boys with SLI. The boys with autism were divided into those with language impairment (ALI) and those with normal language ability (ALN). Subjects (right-handed, aged 6.2-13.4 years) included 22 boys with autism (16 ALI and 6 ALN), 9 boys with a history of or present SLI, and 11 normal controls. MRI brain scans were segmented into grey and white matter; then the cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere. Group differences in volumetric asymmetry were predicted a priori in language-related regions in inferior lateral frontal (Broca's area) and posterior superior temporal cortex. Language impaired boys with autism and SLI both had significant reversal of asymmetry in frontal language-related cortex; larger on the right side in both groups of language impaired boys and larger on the left in both unimpaired language groups, strengthening a phenotypic link between ALI and SLI. Thus, we replicated the observation of reversed asymmetry in frontal language cortex reported previously in an independent autism sample, and observed similar reversal in boys with SLI, further strengthening a phenotypic link between SLI and a subgroup of autism. Linguistically unimpaired boys with autism had similar asymmetry compared with the control group, suggesting that Broca's area asymmetry reversal is related more to language impairment than specifically to autism diagnosis.     

Factors influencing the decision to perform carotid endarterectomy

Various interpretations of the indications for carotid endarterectomy exist. Physician knowledge as it relates to the decision to proceed or recommend carotid endarterectomy was investigated, using disaggregate discrete choice analysis. Canadian neurologists, neurosurgeons, vascular surgeons, and internists were surveyed. The degree of stenosis was most important, followed by symptoms, comorbid illness, and arterial imaging modality. No differences existed by specialty. Canadian physicians in four specialties are knowledgeable about results of randomized clinical trials for carotid endarterectomy.     

Congruence on medication between patients and physicians involved in patient course

Objective To analyse congruence on medication throughout patient courses, including an acute admission to a medical department.Design A prospective, observational study. Data were collected from patient records in primary health care, hospital departments, from the Health Insurance database and through patient interviews.Setting Departments of internal medicine, general practice and patients homes.Main outcome measures Number, type and character of discrepancies between paired sources of information on patient medication at predefined time points throughout the complete patient course. Assessment of likelihood and severity of potential untoward effects of discrepancies.Results Data were obtained for 75 of 99 consecutive patients included. Patients stated use of four drugs (median, range 0–17) at admission, five (0–16) at discharge and four (0–15) 1 month after discharge. At admission, 11 patients used no drugs. A median of one (0–20) to three (0–16) discrepancies per patient were identified in seven paired source comparisons with no improvement along patient course. Full agreement throughout the course was found in six patients (8%; 95% confidence interval: 3–17%). No association was found among source discrepancies and number of drugs and age. Of discrepancies, 4–13% were considered serious and likely to cause untoward effects. Discrepancies due to synonymous and analogous drugs accounted for 2–7% of the discrepancies.Conclusion Congruence between sources of information on medication throughout patient courses cannot be obtained with separate medication charts. Discrepancies among patient, general practitioner and hospital give rise to a definitive risk of serious untoward effects.     

IgH PCR of zinc formalin-fixed,paraffin-embedded non-lymphomatous gastric samples produces artifactual "clonal" bands not observed in paired tissues unexposed to zinc formalin

Helicobacter pylori (HP) causes dense gastritis that can be difficult to distinguish morphologically from MALT-type lymphoma (ML). Immunoglobulin heavy chain (IgH) gene analysis by polymerase chain reaction (PCR) is often used to resolve diagnosis. However, monoclonal bands have been reported in nonmalignant cases of gastritis. Retrospectively, 16 gastric ML with both formalin-fixed, paraffin-embedded (FF-PE) and ethanol-fixed samples (EF), and 9 cases of FF-PE HP-gastritis were analyzed by IgH PCR to document the presence of non-reproducible bands in HP-gastritis, but not ML samples. In duplicate analyses, 12 of 16 ML yielded identical monoclonal bands in FF-PE and EF samples whereas 3 of 9 FF-PE gastritis cases yielded different-sized (ie, non-reproducible) “clonal” bands. Sequencing of two PCR products from a gastritis case confirmed IgH gene sequences. To investigate whether FF-PE had a direct effect on producing these non-reproducible bands, 7 gastrectomy samples were prospectively divided into EF and FF-PE halves for IgH PCR. All 7 samples demonstrated polyclonal smears in EF portions while 4 of 7 FF-PE portions yielded either multiple distinct bands or non-reproducible bands. In conclusion, IgH PCR of FF-PE tissue can create artifactual “clonal” bands, which are the appropriate product size, contain IgH sequences, and, if not performed in duplicate, may confuse interpretation of B-cell clonality.     

Quality of life during radiotherapy for rectal cancer

The aim of this study was to assess symptoms and health-related quality of life (HRQL) during (neo)adjuvant radiotherapy for rectal cancer. Patients receiving pelvic radiotherapy 50 Gy for rectal cancer, were studied prospectively (n=42). The European Organization for Research and Treatment of Cancer (EORTC) questionnaires quality of life-core 30 QLQ-C30 and QLQ-CR38 and a 5-day symptom diary were completed at the start and end of radiotherapy and 4-6 weeks later. At the end of radiotherapy, mean scores of diarrhoea, fatigue and appetite loss had significantly increased (P<0.01) compared with pretreatment scores, but this was not observed for scores for nausea or pain. At the end of radiotherapy, diarrhoea, fatigue, appetite loss, physical function, social function and global quality of life (QL) were significantly worse than the population-based norms. 64% of the patients reported an increase in fatigue and 52% an increase in diarrhoea during radiotherapy. HRQL scores had returned to pre-treatment levels 4-6 weeks after radiotherapy. Thus, diarrhoea, fatigue and appetite loss increased transiently during pelvic radiotherapy.     

Prognostic value of neuroendocrine serum markers and PSA in irradiated patients with pN0 localized prostate cancer

BACKGROUND: The prognosis of patients with localized prostate cancer depends on clinical stage, histological grade, and pretreatment prostate-specific antigen (PSA). We evaluated the additional prognostic impact of serum levels of neuron-specific enolase (NSE) and chromograninA (CgA) after curative radiotherapy and the importance of serum PSA, analyzed 3 months after irradiation. METHODS: From 1988 to 1995, 161 patients with localized T1-4, pN0M0, prostate adenocarcinoma were treated with external radiation (66Gy, 2Gy/5 fractions per week). Frozen serum samples were assessed for CgA, NSE, and PSA before and 3 months after radiotherapy. CgA was analyzed in only 100 patients. NSE and CgA were determined by a immunometric assay. Total PSA was measured by a time-resolved fluoro-immunometric assay. RESULTS: Prior to radiotherapy CgA was elevated in 16 of 100 patients, and NSE was elevated in 33 of the 161 patients. There was no association between grade, T category or pretreatment PSA and the levels of neuroendocrine markers. Pretreatment-elevated serum NSE, but not initial CgA, identified patients with an unfavorable prognosis. A < 50% reduction of PSA 3 months after radiotherapy was associated with decreased failure-free 10 years urvival. Multivariate analysis demonstrated an increased risk of failure for patients with elevated pretreatment NSE and PSA values, T3 category, and decline of PSA less than 50% 3 months after radiotherapy. The presence of none or several risk factors (1-4) defined clearly separable groups. CONCLUSIONS: Together with T category and pretreatment serum PSA values, serum NSE values before radiotherapy and decrease of serum PSA 3 months after radiotherapy represent easily assessable prognostic parameters in patients undergoing curative radiation treatment for prostate cancer.     

Antiphospholipid antibody syndrome. A literature review

Antiphospholipid syndrome (APS) occurs as a primary or secondary syndrome and has various manifestations, including arterial and venous thrombosis, thrombocytopenia, fetal loss, livedo reticularis, and cardiac and neurological sequelae. APS is linked with autoantibodies that were originally thought to have specificity for negatively charged phospholipids. Recent data suggest specificity for different phospholipid-binding plasma proteins, including 2-glycoprotein I, prothrombin, protein C, and protein S. The most well-known antiphospholipid antibodies are lupus anticoagulant and anticardiolipin antibody. These antibodies are detected through lupus anticoagulant assays, anticardiolipin assays, and certain serologic tests for syphilis. This article describes 2 cases encountered in our clinical work and reviews the literature on APS.     

p53, p21 and mdm2 expression vs the response to radiotherapy in transitional cell carcinoma of the bladder

OBJECTIVE: To identify, in a retrospective study, possible molecular markers predictive of radioresponsiveness in patients with transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Patients with T2-T4a TCC treated with preoperative radiotherapy and cystectomy were included in the study if their cystectomy specimen was pT3b (in 42) or pT0 (in 17). Because treatment schedules changed over time, radiotherapy was given either as 2 Gy x 23 over 4-5 weeks with cystectomy 4-5 weeks later (in 23), or as 4 Gy x 5 during 1 week with cystectomy in the following week (in 36 patients). Protein expression of p53, mdm2 and p21 (CDKN1 A/WAF1/CIP1/SDI1) was assessed immunohistochemically in biopsies taken before radiotherapy. RESULTS: There was no difference in protein expression when comparing all patients with pT0 and pT3b. However, for patients receiving 46 Gy, increased p53 expression (but not p21 or mdm2) predicted the absence of residual tumour (P = 0.005): six of seven patients with > 50% p53 expression had pT0 in the cystectomy specimen, whereas 10 of 12 patients with < or = 5% expression had pT3b. Over-expression of p53 correlated with longer overall (P = 0.045) and cancer-specific survival (P = 0.020). CONCLUSION: The expression of mdm2 or p21 did not predict radioresponsiveness in patients with TCC of the bladder. The role of p53 remains unclear; the view that p53 over-expression confers radioresistance in bladder cancer is not supported.