The prognostic value of intraepithelial and stromal CD3‐, CD117‐ and CD138‐positive cells in non‐small cell lung carcinoma

Al‐Shibli K, Al‐Saad S, Andersen S, Donnem T, Bremnes RM, Busund L‐T. The prognostic value of intraepithelial and stromal CD3‐, CD117‐ and CD138‐positive cells in non‐small cell lung carcinoma. APMIS 2010; 118: 371–82. The major value of prognostic markers in potentially curable non‐small cell lung carcinoma (NSCLC) should be to guide therapy after surgical treatment. Although tumor‐infiltrating T lymphocytes and plasma cells have been documented in NSCLC, a clear association with clinical outcome, especially for the stromal component, has not been well established. The aim of this study was to elucidate the prognostic significance of these cells/markers in the epithelial and stromal compartments of NSCLC. Tissue microarrays from 335 resected, stage I‐IIIA, NSCLC were constructed by duplicate cores from viable neoplastic epithelial and stromal areas. Immunohistochemistry was used to evaluate the infiltration of CD3⁺, CD117⁺ as well as CD138⁺ cells in epithelial and stromal areas. In univariate analyses, increasing numbers of stromal CD3⁺ (p = 0.001) and epithelial CD3⁺ cells (p = 0.004) correlated significantly with an improved disease‐specific survival. No such relation was noted with CD3⁺ or CD117⁺ cells. In the multivariate analysis, stromal CD3⁺ cells was an independent prognostic factor for disease‐specific survival (HR 1.925, CI 1.21–3.04, p = 0.005). Increased presence of the pan T‐cell marker, CD3, which is an independent factor, correlates with improved clinical outcome in NSCLC. This prognostic impact of T cells is clearer in the tumor stroma. Neither plasma cells nor mast cells were prognostic indicators in our cohort.     

Pituitary-Thyroid Function and Thyrotropin,Prolactin and Growth Hormone Responses to TRH in Patients with Chronic Alcoholism

ABSTRACT Basal plasma concentrations of thyroxine (T₄), 3,3′,5-triiodothyronine (T₃), free T₄ index (TF₄I), free T₃ index (FT₃I) reverse T₃, 3,3′,5-triiodothyronine (rT₃), resin T₃ uptake (TR₃U), thyroxine-binding globulin (TBG), thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) as well as thyrotropin releasing hormone (TRH) stimulated TSH, PRL and GH were investigated in 31 consecutive male patients (mean age 41 years) with chronic alcoholism. According to the histology of their liver biopsies the patients were divided into three groups: patients with normal livers, steatosis and cirrhosis. The control group consisted of 30 healthy males. The patients had abstained from alcohol for at least one week when studied, and they were on a nutritionally adequate diet. All had consumed a daily minimum of 52 g ethanol for at least 5 years. None of the patients had severe or decompensated liver disease. The patients had significantly reduced T₃ and rT₃ plasma levels compared to normals. Patients with cirrhosis of the liver had increased TBG and normal RT₃U levels, while those without cirrhosis had increased RT₃U and normal TBG levels. Plasma concentrations of basal as well as TRH-stimulated TSH and PRL were unchanged in alcoholic patients, whereas basal as well as stimulated GH levels were increased in cirrhotic alcoholics. It is concluded that alcohol per se influences T₃ levels, but not the part of the hypothalamic-pituitary axis studied, and that the binding proteins are mostly determined by the degree of liver disease.     

SCLERODERMA WITH MASSIVE REGIONAL LYMPHADENOPATHY

Abstract. Scleroderma in a two-year-old boy with gross enlargement of the right inguinal lymph nodes, as an early sign, is reported. Repeated lymph node biopsies revealed non-characteristic reactive changes and hyperplasia, but eventually histological examinations of skin and muscle from the right leg were diagnostic. The effect of one year of D-penicillamine therapy is briefly mentioned.     

Prednisolone in the treatment of severe malignant hypercalcaemia in metastatic breast cancer: a randomized study.

To determine the effect of prednisolone on severe hypercalcaemia in women with metastatic breast cancer, 30 patients with serum ionized calcium above 1.60 mmol l-1 (reference range 1.15-1.35 mmol l-1) entered a randomized trial. Performance status before entry to the trial and survival time after hypercalcaemia were also noted. All patients received 4 l of isotonic saline daily and 80 mg intravenous furosemide three times daily for 2 d; thereafter they received 3 l of isotonic saline daily and 80 mg furosemide twice daily for 6 d. Fifteen patients were randomized to receive prednisolone, 25 mg orally, three times daily for 8 d. Serum ionized calcium decreased significantly in both groups, but most markedly in the prednisolone group. The median difference was 0.28 mmol l-1 (95% confidence interval (CI), 0.09-0.52) on day 4 and 0.21 mmol l-1 (95% CI, 0.12-0.44) on day 8. In seven prednisolone-treated patients serum ionized calcium normalized, compared to none in the control group (Fisher's exact test; P = 0.028). No severe adverse effects were observed. Prior to detection of hypercalcaemia all patients were severely immobilized, primarily due to bone pain. Only 10 patients were still living after 3 months. Prednisolone, furosemide and rehydration is superior to furosemide and rehydration alone in severely hypercalcaemic patients with metastatic breast cancer in whom immobilization appears to be an early warning sign of life-threatening hypercalcaemia. The short survival time was not influenced by prednisolone.     

Dental avoidance behaviour in parent and child as risk indicators for caries in 5-year-old children

Aim.  The aim of this study was to explore associations between avoidance behaviour and dental anxiety in both parents and children and caries experience in 5-year-old children. It was hypothesised that parents' dental avoidance behaviour and dental anxiety were related to dental caries in 5-year-old children.
Design.  Data were collected from dental records and by clinical and radiographic examination of 523 children. The parents completed a questionnaire regarding education, national background, dental anxiety, dental attendance, and behaviour management problems. Bivariate and multivariate logistic regression was conducted.
Results.  Children having one or more missed dental appointments (OR = 4.7), child behaviour management problems (OR = 3.3), child dental anxiety (OR = 3.1), and parents avoiding dental care (OR = 2.1) were bivariately associated with caries experience at the age of 5 years. In multivariate logistic regression, having one or more missed dental appointments (OR = 4.0) and child behaviour management problems (OR = 2.4) were indicators for dental caries in 5-year-old children, when controlling for parents education and national origin.
Conclusion.  Parents that avoid bringing their child to scheduled dental appointments and previous experiences of behaviour management problems for the child indicated risk for dental caries in 5-year-old children.     

A Canine Model of Torsades de Pointes

Although quinidine has been reported to induce QT interval prolongation and torsades de pointes clinically, the only experimental model currently available for quinidine-induced torsades de pointes requires the concurrent use of ischemia, reperfusion and cardiac pacing of the isolated, perfused heart. Our purpose in this study was to determine the circumstances under which quinidine might elicit torsades de pointes consistently in the intact dog. We found that maintenance of therapeutic plasma quinidine concentrations, alone, did not induce the arrhythmia. Rather, arrhythmia induction required the additional application of aconitine, which induces early afterdepolarizations and triggered activity. When aconitine was applied to two epicardial sites in dogs having quinidine-induced QT interval prolongation greater than 10%, torsades de pointes occurred in 80% of instances. When QT prolongation was less than 10%, aconitine-induced torsades de pointes was seen in only 21% of animals. Our results suggest that in a previously healthy heart quinidine-induced QT prolongation is, itself, insufficient to induce torsades de pointes consistently, and two independent sites of ectopic activity are needed as well. The ectopic foci appear to modulate one another's impulse initiation or activation sequence, thereby giving rise to the classical "twisting of the points" associated with the arrhythmia.     

Salmonella or Campylobacter gastroenteritis prior to a cancer diagnosis does not aggravate the prognosis: a population‐based follow‐up study

Gradel KO, Nørgaard M, Schønheyder HC, Dethlefsen C, Ejlertsen T, Kristensen B, Nielsen H. Salmonella or Campylobacter gastroenteritis prior to a cancer diagnosis does not aggravate the prognosis: a population‐based follow‐up study. APMIS 2010; 118: 136–42. We hypothesized that preceding zoonotic Salmonella or Campylobacter gastroenteritis aggravated the prognosis in cancer patients. Exposed patients comprised all of those diagnosed with first‐time Salmonella/Campylobacter gastroenteritis from 1991 and with first‐time cancer diagnosis thereafter (through 2003) in two Danish counties. These patients were matched for main cancer type, gender, age and calendar period to unexposed cancer patients, i.e. those without Salmonella/Campylobacter gastroenteritis. We compared cancer stage by age‐ and comorbidity‐adjusted logistic regression analysis, survival by comorbidity‐adjusted Cox’s regression analysis and mortality dependent on the time period between Salmonella/Campylobacter gastroenteritis and cancer by spline regression curves. The study cohort comprised 272 Salmonella/Campylobacter‐exposed cancer patients and 2681 unexposed cancer patients. Prevalence odds ratios [95% confidence intervals (CI)] in exposed as compared with unexposed patients were 0.96 (0.74–1.25) for localized tumours, 1.15 (0.87–1.54) for regional spread and 1.14 (0.84–1.55) for metastases. Adjusted mortality rate ratios (95% CI) were 0.93 (0.75–1.16) for 0–1 year, 1.08 (0.84–1.39) for 2–5 years and 1.02 (0.60–1.73) for the remaining period. Mortality estimates did not change in relation to the time period between gastroenteritis and cancer. Salmonella/Campylobacter gastroenteritis prior to cancer was associated with neither the cancer stage nor a poorer prognosis.