Combined bilateral submandibular and sublingual swelling, macroglossus, and carpal tunnel syndrome caused by light chain amyloidosis

Three cases of light chain kappa amyloidosis in multiple myeloma patients are described with remarkable involvement of the tongue and swelling of the sublingual and submandibular regions, and without signs of nephropathy despite Bence Jones kappa proteinuria. All three patients had carpal tunnel syndrome at the beginning of their disease course and only moderate gastrointestinal involvement. Primarily for prognostic reasons, amyloidosis should be suspected in such cases, even in the presence of these highly unusual manifestations, and the diagnosis should be confirmed by unambigously-positive biopsies.     

Fluvoxamine inhibits the CYP2C19-catalysed metabolism of proguanil in vitro

OBJECTIVE: The potent CYP1A2 inhibitor fluvoxamine has recently been shown also to be an effective inhibitor of the CYP2C19-mediated metabolism of the antimalarial drug proguanil in vivo. The purpose of the present study was to confirm this interaction in vitro. METHODS: A high-performance liquid chromatography (HPLC) method was developed to assay 4-chlorophenylbiguanide (4-CPBG) and cycloguanil formed from proguanil by microsomes prepared from human liver. The limit of detection was 0.08 nmol mg-'. h-I. RESULTS: The formation of 4-CPBG and cycloguanil could be described by one-enzyme kinetics, indicating that the formation of the two metabolites is almost exclusively catalysed by a single enzyme, i.e. CYP2C19 within the concentration range used, or that the contribution of an alternative low-affinity enzyme, probably CYP3A4, is very low. This notion was confirmed by the lack of potent inhibition by four CYP3A4 inhibitors: ketoconazole, bromocriptine, midazolam and dihydroergotamine. Fluvoxamine was a very effective inhibitor of the oxidation of proguanil, displaying Ki values of 0.69 micromol x l(-1) for the inhibition of cycloguanil formation and 4.7 micromol x l(-1) for the inhibition of 4-CPBG formation. As expected, the CYP2C19 substrate omeprazole inhibited the formation of both metabolites with an IC50 of 10 micromol x l(-1). Norfluoxetine and sulfaphenazole inhibited proguanil oxidation with Ki values of 7.3-16 micromol x l(-1), suggesting that the two compounds are moderate inhibitors of CYP2C19. CONCLUSIONS: Fluvoxamine is a fairly potent inhibitor of CYP2C19 and it has the potential for causing drug-drug interactions with substrates for CYP2C19 such as imipramine, clomipramine, amitriptyline and diazepam. The combination of fluvoxamine and proguanil can not be recommended.     

Functional morphology of nucleolus organizer regions of chromosomes and nucleoli in human multiple myeloma cell lines. I. Variation of the morphology and silver staining of nucleolus organizer regions of chromosomes in RMPI 8226 and U 266 cell lines with different level of differentiation of during 7 days after cell passage

The morphology and Ag-staining of nucleoli in human multiple myeloma cell lines RPMI 8226 and U 266, distinguished from each other in the differentiation degree, were quantitatively studied, and the production of immunoglobulins or their fragments by the line cells was evaluated throughout 7 days after cell seeding. The less differentiated cell line RPMI 8226 and the high differentiated cell line U 266 were revealed to differ in both the initial level of immunoglobulin production and dynamics of immunoglobulin accumulation in culture medium. The total number of Ag-stained nucleolar-organizer regions (AgNORs) per nucleus in cells RPMI 8226 was significantly higher than in cells U 266 in all times after seeding of the cells. In both cell lines changes in the quantity and shape of nucleoli and also in the total number of AgNORs per nucleus and pattern of AgNORs distribution within nucleoli correlated with the cell cycle phase. Relationships between morphofunctional changes in nucleoli and the differentiation degree and proliferative activity of the cells, and also between the number of Ag-positive nucleolar-organizing metaphase chromosomes and the functional activity of interphase AgNORs are discussed.     

Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.     

Occupational medicine in general practice. A study of the extent and nature of occupational injuries in the county of Ringkj?bing

The purpose of this investigation was to estimate the occurrence and type of work-related incidents in primary health care in the county of Ringkoebing, Denmark, with 270,000 inhabitants. Symptom-related general practitioner (GP)-consultations among 17-66 year-old residents were registered among 114 GP's during four days over one year. In each occasion the GP evaluated the question of work-relatedness versus none-work-relatedness. Of 3017 registered consultations, 479 were work-related (15.9%). There were 376 disease cases and 103 injury cases. Musculoskeletal diseases constituted the dominating diagnostic category, as well as being the category with the highest proportion of work-relatedness, corresponding to 35% of all musculoskeletal consultations. Notification as a work injury case was performed for 19% of all work-related cases. This investigation represents the hitherto most extensive Danish material of the distribution of work-related incidents within the broad spectrum of the GP's practice.     

Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium

The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.     

Favourable effect of olive oil in patients with non-insulin-dependent diabetes. The effect on blood pressure, blood glucose and lipid levels of a high-fat diet rich in monounsaturated fat compared with a carbohydrate-rich diet

The aim of the study was to elucidate the role of the neuropeptide galanin in the regulation of somatotropic and gonadotropic function in normal women. Thirteen normally ovulating (aged 28 to 40 years), non-obese (body mass index, 18.4 to 27.1 kg/m2) women with infertility due to a tubal or male factor were studied. Each woman underwent three tests: (1) bolus intravenous (IV) injection of growth hormone (GH)-releasing hormone (GHRH) (1-29)NH2 1 microgram/kg plus gonadotropin-releasing hormone (GnRH) 100 micrograms at time 0; (2) IV infusion of porcine galanin 500 micrograms in 100 mL saline from -10 minutes; and (3) bolus IV injection of GHRH(1-29)NH2 1 microgram/kg plus GnRH 100 micrograms at time 0 plus IV infusion of porcine galanin 500 micrograms in 100 mL saline from -10 to +30 minutes. All results are expressed as the mean +/- SEM. GH peak after GHRH was 14 +/- 5 micrograms/L; porcine galanin significantly increased serum GH (GH peak, 7.3 +/- 1.2) with respect to baseline levels. No significant differences were observed between either GH peak or GH absolute values after galanin as compared with GHRH alone. Porcine galanin significantly enhanced GH response to GHRH (peak, 31.4 +/- 4.4 micrograms/L) with respect to either GHRH or galanin alone. Luteinizing hormone (LH)/follicle-stimulating hormone (FSH) peaks after GnRH were 16.5 +/- 5.3 and 17.4 +/- 4 IU/L, respectively. Porcine galanin did not cause significant increases in serum LH and FSH levels with respect to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metachromatic leukodystrophy and coincidental finding of papillomatosis of the gallbladder. A case report

In this case report we describe the coincidental finding of polyps in the gallbladder by ultrasound investigation in a six-year-old girl, known to have metachromatic leukodystrophy. The investigation was carried out because of suspicion of abdominal trauma after falling down the stairs and finding elevated serum amylase.