The validity of C-peptide measurement in the diagnosis of factitious hypoglycemia

Summary The case is presented of a 32-year-old obese diabetic nurse, with a history of recent hypoglycemic episodes. Estimation of immunologically measurable insulin during hypoglycemia after an overnight fast revealed high values, while simultaneous determination of serum C-peptide failed to show an increase. This combination is considered pathognomonic for factitious hyperinsulinism. After the hidden vial was discovered and presented to her, the patient finally admitted that she had been surreptitiously injecting insulin. Supported by grants from Social Ministry, Athens, Greece, and the Department of Internal Medicine I (Endocrinology, Metabolism and Immunology), University of Ulm, FRG.     

Unilateral emphysematous pyelonephritis.

A case of unilateral emphysematous pyelonephritis is presented in a patient with uncontrolled diabetes mellitus. The diagnosis was established from the presence of gas in the renal parenchyma, the pelvicalyceal system and the ureter. The patient was treated with a prolonged course of antibiotics and the function of the left kidney returned to normal.     

Serum adiponectin concentrations and tissue expression of adiponectin receptors are reduced in patients with prostate cancer: a case control study.

PURPOSE: Adiponectin, an adipocyte-secreted hormone with insulin-sensitizing effects, has been inversely associated with several hormonally dependent malignancies, including breast, endometrial, and colorectal cancer. Few studies have examined serum adiponectin in relation to prostate cancer, and expression of adiponectin receptors has previously not been assessed in prostate tumors. EXPERIMENTAL DESIGN: We collected plasma samples and covariate data in the context of a case-control study of 300 Greek men, including 75 prostate cancer cases, 75 patients with benign prostatic hyperplasia (BPH), and 150 healthy controls. Prostate tissue samples were taken from 72 cases and 27 noncases and examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry. RESULTS: Prostate cancer patients had significantly lower plasma adiponectin concentrations as compared with men with BPH and healthy controls (7.4 +/- 5.0 versus 11.5 +/- 6.4 and 12.8 +/- 8.0 ng/mL, respectively). Men in the top two quartiles of adiponectin had a 71% to 73% reduced risk of prostate cancer as compared with men in the lowest quartile after adjusting for age, body mass index, and additional potential confounders. We found no similar relationship between adiponectin and risk of BPH. Results from immunohistochemistry experiments show weaker expression of adiponectin receptors AdipoR1 and AdipoR2 in cancerous versus healthy prostate tissue. CONCLUSIONS: Higher serum adiponectin is associated with a marked reduction in risk of prostate cancer, but not BPH, independently of other risk factors. Malignant prostate tissue samples have reduced expression of adiponectin receptors as compared with benign prostate tissue. These results support a role for adiponectin in the pathogenesis of prostate cancer.     

Immune abnormalities in myelodysplastic syndromes

The immune states of 52 patients with myelodysplastic syndromes classified according to the FAB criteria were studied. Serum electrophoresis and immunoelectrophoresis, direct Coombs test, and tests for organ and non-organ specific antibodies were performed. Twenty six patients had immunoglobulin abnormalities: six (11.5%) had monoclonal gammopathy; 17 (32.6%) had polyclonal increases in serum immunoglobulin; while in three (5.8%) immunoglobulin concentrations were decreased. The distribution of immunoglobulin abnormalities among the five myelodysplastic syndrome subtypes was fairly uniform. Results of direct Coombs test were negative in all cases. Organ specific antibodies were not detected in any of the patients tested, although two patients were found positive for antinuclear antibodies. The presence of immunoglobulin abnormalities indicates an involvement of the lymphoplasmatic system in myelodysplastic syndromes.     

Cytoplasmic and nuclear progestin receptors in human myometrium during the menstrual cycle and in pregnancy at term

Exchange assays have been developed for the determination of the total progestin in receptor sites (unoccupied and occupied with endogenous hormone) in the cytosol and nuclei of human myometrium using radiolabeled R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) as ligand. These assays have been applied to the measurement of cytosol and nuclear progestin receptor sites in the myometrium during the menstrual cycle and in pregnancy at term. Both the cytosol receptor levels as well as the sum of cytosol and nuclear receptor levels were highest during the proliferative phase of the cycle, dropped moderately but significantly in the secretory phase, and decreased markedly in pregnancy at term. Despite the marked drop in cytosol receptor levels, nuclear receptor levels in pregnancy at term were similar to those observed in the proliferative or secretory phase. In addition, the fraction of the total cellular receptor that was associated with the nucleus increased from 5.5% in the proliferative phase to 60% in pregnancy at term. The decrease in cytosol progestin receptor concentration as well as the relative increase in nuclear localization of the receptor in human myometrium in pregnancy at term may be related to the high circulating progesterone levels.     

Expression of RHAMM/CD168 and other tumor-associated antigens in patients with B-cell chronic lymphocytic leukemia

Antigen targeted immunotherapies might represent a novel treatment for B-cell chronic lymphocytic leukemia (B-CLL). We screened the mRNA expression of tumor-associated antigens (TAAs) from the literature (fibromodulin, survivin, OFA-iLRP, BAGE, G250, MAGE1, PRAME, proteinase, syntaxin, hTERT, WT-1) and TAAs defined previously by serological analysis of cDNA expression libraries from leukemic cells (PINCH, HSJ2, MAZ, MPP11, RHAMM/CD168, NY-Ren60). Peripheral blood mononuclear cells from 43 B-CLL patients and 20 healthy volunteers (HVs) were examined by conventional and quantitative RT-PCR. mRNA of RHAMM/CD168, fibromodulin, syntaxin and NY-Ren60 was expressed in 55-90%, and mRNA of HSJ2, MAZ and OFAiLRP was expressed in 90-100% of the patients. No expression of WT-1, hTERT, BAGE, G250, MAGE1 or survivin was observed. Low (2-20%) expression frequencies of MPP11, PINCH, PRAME and proteinase were detected. RHAMM/CD168, fibromodulin, PRAME and MPP11 showed expression in B-CLL patients, but not in HVs. Because of the exquisite tissue expression of RHAMM/CD168 and its high expression frequency in CLL patients, mixed lymphocyte peptide culture (MLPC), enzyme-linked immunosorbent spot (ELISPOT) and flow cytometry were performed for antigen specific T-cells. In MLPC, RHAMM specific responses by CD8+HLA-A2/R3tetramer+CCR7-CD45RAhigh effector T-cells were detected. RHAMM/CD168 might be a possible target for future immunotherapies in both ZAP-70(+) and ZAP-70(-) B-CLL patients.     

Liposomal cisplatin combined with gemcitabine in pretreated advanced pancreatic cancer patients: a phase I-II study

The present trial is a phase I-II study based on a new liposomal cisplatin (lipoplatin). Previous preclinical and clinical data (phase I pharmacokinetics) led to the investigation of a combined treatment modality involving lipoplatin and gemcitabine. The gemcitabine dose was kept standard at 1000 mg/m2 and the lipoplatin dose was escalated from 25 mg/m2 to 125 mg/m2. The treatment was administered to advanced pretreated pancreatic cancer patients who were refractory to previous chemotherapy which included gemcitabine. Lipoplatin at 125 mg/m2 was defined as dose limiting toxicity (DLT) and 100 mg/m2 as the maximum tolerated dose (MTD) in combination with 1000 mg/m2 of gemcitabine. Preliminary objective response rate data showed a partial response in 2/24 patients (8.3%), disease stability in 14 patients (58.3%) for a median duration of 3 months (range 2-7 months) and clinical benefit in 8 patients (33.3%). Liposomal cisplatin is a non-toxic alternative agent to bare cisplatin. In combination with gemcitabine, it has an MTD of 100 mg/m2 and shows promising efficacy in refractory pancreatic cancer.     

Disappearance of a growth hormone secreting macro adenoma during long-term somatostatin analogue administration and recurrence following somatostatin withdrawal

Acromegaly is caused by excessive growth hormone secretion, usually from a pituitary adenoma. The use of somatostatin analogues as primary or adjunctive therapy has been widely applied in the management of acromegaly. We are aware of only three reported cases of complete shrinkage of a pituitary adenoma after long-term analogue administration. However in these cases, the reduction in the dimension of the adenoma was obtained with the everyday use of somatostatin analogues and not with the newer longer acting formulations. We report a patient in whom long term (62 months) lanreotide-L.A.R administration resulted in complete disappearance of a growth hormone secreting pituitary macroadenoma, followed by recurrence of the adenoma six months post therapy discontinuation.