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Resume Une observation de fausse hyperphosphoremie decouverte chez un patient atteint d'un myelome multiple a IgG est rapportee. La phosphoremie, mesuree suivant une technique sans deproteinisation preliminaire du serum atteignait 5,66 mM avant tout traitement. Elle variait suivant les modifications du taux de l'immunoglobuline monoclonale induites par le traitement. La phosphoremie etait par contre trouvee a des valeurs normales sur des echantillons sanguins recueillis avant ou apres traitement lorsque le serum etait deproteinise. La fausse hyperphosphoremie etait provoquee par une augmentation de la densite optique due a une interference entre l'immunoglobuline monoclonale et le reactif molybdique utilise pour determiner la phosphoremie. Une enquete retrospective a permis de decouvrir 3 observations similaires, deux chez des patients atteints de myelome, une au cours d'une dysglobulinemie monoclonale non myelomateuse. Une breve etude prospective montre la relative frequence du phenomene, decouvert 2 fois chez 9 patients porteurs d'une immunoglobuline monoclonale. Il s'agissait dans tous les cas d'une IgG. Ces observations montrent que la decouverte d'une hyperphosphoremie elevee chez un sujet presentant une dysglobulinemie monoclonale doit toujours faire pratiquer un controle sur sang deproteinise.

Mesenchymal hamartoma is a rare liver lesion. This lesion was found in a 7-month-old girl with high serum alphafaetoprotein serum levels and was composed of loose connective tissue containing a certain number of epithelial cells of biliary or hepatic origin. Immunohistochemical studies showed that cytokeratins 7 and 19 were localized in bile duct epithelium. The ultrastructural study showed that the hamartoma was composed of well differentiated ductal structures surrounded by a myxoid mesenchyma with cysts formed either from degenerative mesenchymal areas or from dilated ducts. Flow cytometric analysis of nuclei from frozen tissue revealed that the lesion was DNA aneuploid, with a DNA index of 1.28.

Thirty-two consecutive subtrochanteric fractures in 32 patients were stabilized using the Medoff sliding plate and were followed up prospectively for 1 year. Two patients died during the first postoperative year. Twenty-nine of the remaining 30 (97%) fractures united by 1-year followup. Two types of plate dynamization schema were used: uniaxial (17 patients) and biaxial (15 patients). With uniaxial dynamization, plate sliding averaged 12 mm along the femoral shaft without medialization of the femoral shaft. With biaxial dynamization along the femoral shaft and the neck, plate sliding averaged 11 mm and screw in barrel sliding averaged 9 mm; medialization of the femoral shaft ranged from 0% to 35% of the femoral shaft diameter. Three fractures treated with uniaxial dynamization had migration of the lag screw within the femoral head; all three fractures united without additional screw migration after secondary or staged biaxial plate dynamization.

A leaf cDNA library from hybrid aspen, Populus tremula x tremuloides, was constructed. From this two different cDNA clones, denoted CA1a and CA1b, encoding a chloroplastic carbonic anhydrase (CA) were isolated and DNA sequenced. Analysis of the deduced amino acid sequences showed that the isolated CAs belong to the beta-CA family, and have identities around 70% to other dicotyledonous plant CAs. The two hybrid aspen cDNA clones display a high nucleotide sequence identity, only 12 nucleotides differ. Since only one gene copy of this soluble chloroplastic CA is present in the nuclear genome, we postulate that the two isolated cDNA clones are alleles. Northern blot hybridization revealed a CA transcript of ca. 1300 bases, 140 bases shorter than in pea. Western and northern blot hybridizations on crude protein extracts and on total RNA, respectively, isolated from stem and leaves, showed that hybrid aspen CA is expressed specifically in the leaf under the growth conditions used. Based on the deduced amino acid sequence, the mature hybrid aspen CA enzyme subunit has a molecular mass of 24.8 kDa. The enzyme was over-expressed in Escherichia coli, and purified by affinity chromatography. Biochemical characterization showed that the protein structure and the CO2-hydration activity are similar to the pea enzyme. Molecular characterization of a CA from a perennial plant has not previously been performed, and it demonstrates that both the structure and activity of hybrid aspen CA resembles CAs from annual plants.

Objectives Increased risk of lung cancer has been observed among hairdressers mostly in studies that did not adjust for smoking as a confounder; the objective of the present study was to evaluate this in the SYNERGY project while adjusting for smoking. Methods SYNERGY consists of 16 pooled case-control studies conducted in Europe, Canada, China and New Zealand between 1985 and 2010. Lifetime occupational and smoking information was collected through interviews from 19,369 cases of lung cancer and 23,674 matched populations or hospital controls. Hairdressers were identified using the ISCO codes 5–70.20 (women’s hairdresser) and 5–70.30 (men’s hairdresser/barber). Odds ratios (ORs) and 95% confidence intervals (95% CI) of lung cancer risk were estimated using unconditional logistic regression. Results Overall, 170 cases and 167 controls ever worked as hairdresser or barber. The ORs for lung cancer in male hairdressers/barbers were 1.04 (95% CI: 0.79, 1.37) before adjustment for smoking and 0.91 (95% CI: 0.66, 1.25) after, and did not change markedly with regard to the time of employment. The ORs in women were 1.65 (95% CI: 1.16, 2.35) before adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) after; although women employed before 1954 experienced an increased lung cancer risk also after adjustment for smoking (OR 2.66, 95% CI: 1.09, 6.47). Smoking habits differed in female hairdressers vs. non-hairdressers, while there was no significant difference in smoking habits between male hairdressers/barbers and non-hairdressers/barbers. Conclusion Our results suggest that most findings of increased lung cancer risk among hairdressers are likely due to smoking behaviour among this occupational group and not directly related to occupational exposure.

The Stripa Project, on geologicaldisposal of radioactive waste, has been completed after a 15-year cooperative international research effort. This article summarizesthe results of research and development on methods to characterize the flow and transport properties of a fractured rock mass for repository site evaluation. The approach used, and the flow and transport experiments conducted, provide new data and permit a comparison ofmodel predictionswith large-scalefieldmeasurements. The 3D discrete fracture models used in this research gave good predictions of flowand transport to sinkscreated by boreholesbut werenot ableadequatelyto representexcavation induced changes to drift inflows.

The temperature distribution, the buoyancy head and the flow rate have been studied in a counter flow heat exchanger having buoyancy driven flow on at least one side. The assumptions made for heat flux distribution are varied and the resulting effects on the flow rate and fluid temperatures are studied. A network model is used to simulate the temperature distribution and oil flow rates in an oil-filled power transformer cooled by radiators. It is found that for operating conditions normally found for mineral oil the counter flow assumptions for heat flux distribution gives approximately the same results as assuming uniform heat flux. When a more viscous oil type is used or the radiators are placed lower than normal relative to the heat generating parts, the counter flow assumptions give more reliable results.

Since liposomes are slowly resorbed from serous cavities, they may constitute a valuable tool for the treatment of peritoneal carcinomatosis. We prepared mitoxantrone (MXN)-liposomes with various lipid compositions and checked their antitumoral activity on a peritoneal carcinomatosis induced by a colon cancer cell injection (1 x 10(5) C51 cells) in BALB/c mice. MXN entrapment in liposomes was rapid and stable due to its high lipophilicity. MXN carried in phosphatidylcholine: cholesterol (2:1; G-liposomes) displayed a reduced toxicity in mice compared to the free drug. When tested at a non-toxic dose (2 mg/kg), MXN entrapped in G-liposomes proved to be as efficient as the free drug. At a higher MXN dose (3 mg/kg), both G-liposomes and phosphatidylcholine:cholesterol:dipalmitoylphosphatidylethanolamine (7:2:1) liposomes, loaded with MXN, significantly increased the life span of mice compared to the free drug and six other liposome formulations. Increase in the MXN therapeutic index, when used in the liposomal form, could then merit further clinical investigations in regard to patients with malignancies confined to serous cavities.

Many non-malignant diseases may be associated with elevated serum CA19-9 levels. Recent reports suggest that diabetes mellitus may also be responsible for some elevations. In this study we investigated the influence of the glycaemic level and Lewis phenotype on the serum CA19-9 levels in diabetic patients. In 15 out of 84 patients (17.8%) serum CA19-9 exceeded 100 kU/L (highest value: 208 kU/L). CA19-9 concentrations were significantly correlated with glycosylated haemoglobin levels. On the other hand, no correlation was found between CA19-9 levels and the type of diabetes, lipase levels, or the presence of anti-islet cell antibodies. Le(a-b-) patients had significantly lower serum CA19-9 levels. This study emphasizes the frequency of CA19-9 elevations in diabetic patients without cancer.

Olsson, S.-O., S. Viring, U. Emanuelson and S.-O. Jacobsson: Calf diseases and mortality in Swedish dairy herds. Acta vet. Scand. 1993,34, 263-269.– A survey of the mortality and morbidity affecting calves during the first 3 months of life was carried out. Results are reported from 131 herds with altogether 5,050 calvings. These herds kept individual calf cards for all calves born. The incidences of abortions and stillborn calves were 0.6% and 3.6%, respectively. During the period 0-90 days the mortality and morbidity were 2.6% and 11.0%, respectively. The frequencies of enteritis and pneumonia in calves were 7.2% and 0.8%. Mortality and morbidity were influenced by breed, season, age of the dam and time of first colostrum. The frequencies of abortions, stillborn calves, mortality and morbidity varied considerably between herds. Herd factors influencing mortality and morbidity during different periods of time were: herd size, yield, zero-grazing, whether the calf was allowed to feed by suckling, the design of the calf pens, and previous incidence of infectious enteritis in the herd. On average, both mortality and morbidity in calves were low, though in certain herds, temporarily high frequencies were registered.

Silicon oxynitride ceramics have been prepared from Si3N4 and SiO2 by pressureless sintering at 1600 and 1775°C and by hot isostatic pressing (HIP) at 1600, 1750 and 1900°C, with Y2O3 (0–10 wt%) as a sintering aid. Pressurelessly sintered samples were in general porous, whereas the HIPed samples were dense at all temperatures. The reaction to form Si2N2O was very sluggish in the absence of Y2O3, and the samples mostly consisted of unreacted starting material, whereas addition of Y2O3 and high temperatures greatly favoured the formation of Si2N2O. Dense Si2N2O materials, prepared by HIP at 1900°C, were hard (HV10 = 1550 kgmm−2) and brittle (K1C = 3.3 MPam1/2) at room temperature for low Y2O3 additions. The hardness decreased slightly, but the fracture toughness remained the same with increasing yttria content.

A case of pseudohyperphosphataemia detected in a male patient with multiple IgG myeloma is reported. Phosphataemia, measured by a technique without previous deproteinization, reached 5.66 mM before any treatment and varied with treatment-induced changes in monoclonal immunoglobulin levels. Conversely, normal phosphataemia levels were found in blood samples taken before and after treatment when serum was deproteinized. This pseudohyperphosphataemia resulted from an increase in optic density due to interference between monoclonal immunoglobulin and the molybdic reagent used to determine phosphataemia. A retrospective investigation yielded three similar cases: two in patients with myeloma and one in a patient with non-myelomatous monoclonal dysglobulinaemia. A brief prospective study showed that this phenomenon was relatively frequent, as it was found in 2 out of 9 patients with monoclonal immunoglobulin (IgG in all 9 cases). These data indicate that the finding of marked hyperphosphataemia in subjects with monoclonal dysglobulinaemia should always prompt a control assay performed on deproteinized blood.

Myasthenia gravis (MG) is strongly associated with antibodies to acetylcholine receptor (AChR), whereas the extent of T cell involvement is not settled. The number of cells secreting interferon-gamma (IFN-gamma) in response to AChR during 48 h culture of blood mononuclear cells (PBL) may reflect AChR-reactive T cells. Using an immunospot assay, we detected such cells in 23 of 30 patients with MG at a mean number of 1 per 33.333 PBL. AChR-reactive T cells were also found in patients with other neurological diseases (OND) and in healthy subjects but at lower frequencies and numbers. The T cell response to purified protein derivative and to PHA, and also to two major myelin proteins (basic protein and proteolipid protein) did not differ between MG and the two control groups, underlining the specificity of an augmented T cell reactivity to AChR in MG. Evaluation of the B cell response by enumerating anti-AChR IgG antibody secreting cells revealed such cells in 27 of 28 patients with MG at a mean value of 1 per 14,085 PBL. Cells secreting anti-AChR antibodies of the IgA and IgM isotypes were also detected in MG, but less frequently, at lower numbers, and only in conjunction with IgG antibody secreting cells. Anti-AChR antibody secreting cells were also found among patient with OND and in healthy controls, but at lower frequencies and numbers. These data confirm that AChR is a major target for autoimmune response in MG.

In a randomized, double-blind, parallel group study, diltiazem was compared with metoprolol as add-on therapy to diuretic treatment in 115 patients with hypertension. Following a placebo and diuretic period of four weeks, patients were randomized to either slow release diltiazem 90 mg twice daily or metoprolol 100 mg once daily using a double dummy technique. If after four weeks a target supine diastolic blood pressure (DBP) less than or equal to 90 mmHg pressure was not reached, the doses of diltiazem and metoprolol were doubled. Supine inclusion systolic/diastolic blood pressures (SBP/DBP) at randomization were 158 +/- 13 (mean +/- SD)/102 +/- 5 mmHg in the diltiazem group and 158 +/- 17/101 +/- 6 mmHg in the metoprolol group. Active therapy significantly lowered SBP and DBP in both groups by 7-10%. Heart rate was significantly lowered in both groups, although the effect of metoprolol was more pronounced. Response rates (supine DBP less than or equal to 90 mmHg and/or decreased by greater than or equal to 10%) were 43% on diltiazem 90 mg twice daily and 52% on metoprolol 100 mg once daily, increasing to 82% and 62%, respectively, after dose escalations. No serious side effects were seen, but three patients, two on diltiazem and one on metoprolol, were withdrawn from the study due to severe headache, nausea and bradycardia respectively. of mild to moderate adverse reactions, tiredness was most frequent, occurring in 14.5% and 15.8% on active diltiazem and metoprolol therapy, respectively. We conclude that both diltiazem and metoprolol lower BP when added to diuretics in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of the bolus dose and the basal infusion during insulin pump treatment on pre- and post-prandial hyperinsulinemia was investigated in 8 insulin-dependent diabetic patients. Frequent determinations of free insulin in blood and simultaneous determination of glucose consumption with euglycaemic clamp technique were made after a bolus of 5 U with or without basal infusion and after 10 U with basal infusion. The maximum free insulin level was reached after 75, 65 and 105 min respectively (median; NS), whereas 50% of the maximum was reached already after 15, 10, and 12.5 min (NS). The fall in free insulin after the peak was slower in all protocols compared to the breakfast induced peak in healthy subjects and it was slower with than without basal infusion (p less than 0.03). Glucose consumption followed the free insulin profiles. We conclude, that administration of a subcutaneous bolus with an insulin pump gives a dose-related free insulin peak that is unphysiological in comparison with the normal meal-related insulin secretion. Preprandial hyperinsulinemia, found after a prescribed interval of 30 min between injection and meal, as well as postprandial hyperinsulinemia, increased with a greater bolus indicating that adjustments of timing of meals and snacks may be necessary when the dose is changed. Furthermore, the insulin substitution with external pumps would probably be more physiological if the basal supply was interrupted after a bolus.

A double-blind, parallel-group multicentre study has been done to compare the antihypertensive properties, effects on serum lipoproteins and adverse effect profiles of diltiazem and metoprolol given as monotherapy to primary hypertensive patients. 128 patients were included from 10 participating centers.

Antibodies to myelin components, such as myelin basic protein (MBP), may play a role in pathogenesis of multiple sclerosis (MS) but results from determinations of anti-MBP antibodies are inconsistent. Enumeration of cells secreting antibodies represents a new approach to evaluate a specific antibody response regarding extent and localization, and reduces effects of e.g. antibody binding to target. Anti-MBP IgG antibody secreting cells were present in MS patients' cerebrospinal fluid (CSF) at a mean value of 1 per 833 cells, and they amounted to a mean value of about 2454 in the whole CSF compartment. Similar numbers were encountered in patients with other inflammatory neurological diseases (OIND). During follow-up, anti-MBP IgG antibody secreting cells persisted regarding frequency and numbers in MS, but decreased in OIND. Such cells were rarely detected in patients with tension headache. No correlations to clinical exacerbation of MS, disability or duration were discernable. In blood from MS and OIND patients, anti-MBP IgG antibody secreting cells were detected infrequently and at low numbers. The anti-MBP antibody response is strongly restricted to the IgG isotype. The anti-MBP IgG antibody response which is persistent and compartmentalized to the diseased organ, may be important for the development of MS.

Cerebrospinal fluid, peripheral blood lymphocytes (PBL) and sera from 5 patients with herpes simplex encephalitis (HSVE), 3 with varicellae zoster (VZV) meningoencephalitis and 5 with encephalitis of unknown origin (NUD) were analyzed. Lymphocytes from both blood and CSF were shown to synthesize anti-VZV IgG subclasses in VZV meningoencephalitis and anti-HSV IgG subclasses in HSVE. The subclass patterns of CSF and in vitro synthesized anti-viral IgG were similar, suggesting that a considerable portion of the antiviral IgG subclasses detected are synthesized in the CNS compartment. Antigen presentation in vitro seemed to produce a heterologous IgG4 and/or 3 response in 3 patients. Lymphocyte proliferation was detectable in response to HSV and VZV, respectively.

SUMMARY By two-colour flow cytometric analysis, we found increased numbers of B cells co-expressing the pan-T cell marker CD5 and the B cell marker CD19 in cerebrospinal fluid (CSF) of 21 patients withmultiple sclerosis (MS), compared with 17 control subjects with muscular tension headache. Only onepatient with MS, but nine controls lacked CD5+ B cells in CSF. This difference was not observed inperipheral blood. Numbers of CD5+19+ B cells were increased in CSF compared with blood in MS, but not in the controls. In both groups, CD5+19+ B cells were not restricted to small restinglymphocytes, but were also found among larger-sized lymphocytes. The relative density of CD5molecules and of CD19 molecules was lower in CD5+ 19+ thaninCD5- 19+ B cells and CD5+ 19- Tcells. CD5+ B cells are assumed to be responsible for auloanlibody production, and our resultssuggest a palhogenetic role of such cells, predominantly within the central nervous system, in MS.

When the B-eell response was examined by enumeration of immunoglobulin (Ig) secreting cells, normal cerebrospinal fluid (CSF) contained IgG secreting cells, indeed at an eight-fold higher proportion per 104 mononuclear cells (MNC) than blood. As expected, the proportion of IgG producing cells is mostly greatly increased in CSF from patients with multiple sclerosis (MS). Evaluation of antibody responses at cellular level (thereby bypassing probable drawbacks inherent in determinations of circulating antibody levels such as antibody binding to target) revealed that in one MS patient group, 57% had in CSF cells secreting IgG antibodies against myelin basic protein (MBP), and in another MS group, 55% had in CSF cells producing IgG antibodies against myelin-assoeiated glycoprotein (MAG); both MBP and MAG are possible targets for immune attack in MS. Anti-MBP and anti-MAG IgG antibody secreting cells could occur in parallel or independently. They were rarely detected in blood, reflecting strong compartmentalization to CSF-CNS. Their possible role in MS pathogenesis is envisaged in light of recently suggested coupling between polyclonal B-cell hyperresponsiveness and antigen-driven specific response in autoimmune-prone individuals.

rosuvastatin (Crestor) is a highly efficacious 3-hydroxy- 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) with a safety profile comparable to those of other marketed statins. AstraZeneca's ongoing review of post-marketed safety data as well as a recent review of data by health authorities worldwide, including the US Food and Drug Administration, supports this conclusion. Because patients' safety is of para- mount importance to AstraZeneca, rosuvastatin was the most extensively studied statin ever submitted for regulatory review. To date, regulatory authorities in more than 60 countries worldwide have approved rosuvastatin on the basis of the excellent benefit-risk profile, and over 2 million patients have now been treated with rosuvastatin. Since rosuvastatin is the statin delivering the greatest reduction in LDL cholesterol (with the advantage of a significant increase in HDL cholesterol), more than 80% of patients can reach their LDL cholesterol goal on the usual start dose of rosuvastatin 10 mg. For the small number of patients with particularly severe hypercholesterolaemia who are inade- quately treated with current monothera- pies, titration to rosuvastatin 40 mg offers a therapeutic option. Rhabdomyolysis is seen with all statins and is observed rarely across the full dose range. With continued marketed experience of rosuvastatin, the reporting rate of rhabdomyolysis has remained very rare by the Council for International Organizations of Medical Sciences' definition (