Insulin sensitivity, adjusted beta-cell function and adiponectinaemia among lean drug-naive schizophrenic patients treated with atypical antipsychotic drugs: a nine-month prospective study.

Atypical antipsychotic drugs (AADs) induce weight gain and truncal adiposity, and even the metabolic syndrome (MetS), which may progress to IFG/IGT or DM. AAD effects in lean schizophrenic patients without MetS have not been documented, especially in terms of weight gain and changes in insulin sensitivity (S), beta-cell function (beta) and adiponectinaemia. We prospectively determined the effects of nine-month therapy with AADs on anthropometrics, metabolism and adiponectinaemia, including homoeostasis model assessment (HOMA) modelling of S, beta and betaxS (hyperbolic product, assessing individual beta adjusted for S). We analyzed 36 schizophrenic subjects (M/F: 24/12; Caucasian: n=23, North African: n=12, South Asian: n=1) aged 35+/- years (mean+/-one S.D.) free of MetS (NCEP-ATPIII), of whom 19 study completers were evaluated following AAD treatment. S, beta, betaxS and adiponectin were measured at zero, three and nine months. At nine months, BMI had risen from 22+/-2 to 25+/-2kg/m(2) (P<0.001) and waist circumference from 85+/-8 to 91+/-11cm (P<0.001), while adiponectin decreased from 10.4+/-5.1 to 7.4+/-3.8mug/mL (P<0.001). Blood pressure and lipids were unaffected. S decreased from 138+/-49 to 110+/-58% (P=0.006) and beta increased from 83+/-24 to 100+/-40% (P=0.034). As a result, betaxS decreased from 106+/-19 to 91+/-27% (P=0.015). Fasting glycaemia rose from 89+/-5 to 96+/-9mg/dL (P=0.007). On study completion, 21% had IFG. Long-term use of AADs in lean, drug-naive, schizophrenics initially free of MetS induced weight gain and truncal fat accumulation associated with decreases in adiponectin and hyperbolic product, explaining the increased fasting glycaemia and impaired fasting glucose seen in predisposed individuals.

Surveillance of antibiotic resistance in non invasive clinical isolates of Streptococcus pneumoniae collected in Belgium during winters 2003 and 2004.

A total of 391 and 424 non-invasive isolates of Streptococcus pneumoniae collected by 15 laboratories during the 2003 and 2004 survey were tested for their susceptibility by a microdilution technique following NCCLS recommendations. Insusceptibility rates (IR) in the two surveys (2003/2004) were as follows: penicillin 15.0/14.7% [8.4/6.4% Resistance (R)], ampicillin 17.4/14.6% (R 9.0/7.1%), amoxicillin +/- clavulanic acid 2.6/1.2 % (R 0/0%), cefaclor 14.3/14.1% (R 11.5/13.4%), cefuroxime 13.6/12.7% (R 10.5/11.8%), cefuroxime-axetil 10.5/11.8% (R 10.0/9.2%) (breakpoints based on 250 mg), cefotaxime 4.9/6.2% (R 1.3/2.4%), ceftazidime NotTested (NT)/6.4 (R NT/2.6%), cefepime NT/6.4 (R NT/2.6%), imipenem 7.7/8.9 % (R 1.8/1.4%), ertapenem 0.8/NT% (R O/NT%), ciprofloxacin 13.8/9.0% (R 4.3/2.4%), levofloxacin 3.3/2.8% (R 1.5/0.2%), moxifloxacin 0.6/0.2% (R 0.3/0%), ofloxacin 13.5/9.0% (R 4.3/2.4%), erythromycin 26.1/24.7% (R 25.3/24.5%), azithromycin 25.4/24.7% (R 24.6/24.5%), telithromycin 0.8/0.2% (R 0.5/0%), clindamycin 21.2/18.4% (R 19.2/17.7%) and tetracycline 32.3/22.1% (R 29.2/19.3%). There were only minor differences in resistance rates according to age, sample site, admission type (i.e. ambulatory, hospitalized or long-term care facility patients), gender and geographic origin. Overall, telithromycin (MIC50, MIC90 in 2003/2004: 0.015 microg/ml, 0.12 microg/ml/ 0.008,0.06 respectively), ertapenem (0.03; 0.25/NT), moxifloxacin (0.06; 0.25/0.06, 0.12), and amoxicillin +/- clavulanic acid (0.03; 0.25/0.015, 0.5) were the most active compounds in both surveys. In 2003, the most common resistance phenotype was isolated insusceptibility to tetracycline (10.5%) followed by combined insusceptibility to erythromycin and tetracycline (9.3%). Erythromycin-tetracycline resistance (10.4%) was the most common in 2004. Isolates showing resistance to an antibiotic were significantly more present in 2003 than in 2004 (50.4% versus 40.8%). In penicillin-insusceptible isolates, MICs of all beta-lactams were increased but cross-resistance between penicillin and other beta-lactams in the penicillin-insusceptible isolates was not complete. In the 2003 survey, most of these isolates remained fully susceptible to ertapenem (94.9%) and amoxicillin +/- clavulanic acid (83.1%). In the 2004 survey, 91.9% of the penicillin insusceptible isolates remained susceptible to amoxicillin +/- clavulanic acid. In both surveys, the most common serotypes in penicillin insusceptible isolates were 14, 23,19 and 9 (20.0%, 20.0%, 16.4% and 10.9% respectively in 2003; 41.6%, 11.7%, 15.0% and 18.3% respectively in 2004).

Surveillance of antibiotic resistance in clinical isolates of Streptococcus pneumoniae collected in Belgium during winter 2000-2001.

A total of 314 isolates of Streptococcus pneumoniae collected by 10 different laboratories were tested for their susceptibility by using a microdilution technique following NCCLS recommendations. The following antibiotics were included: penicillin, ampicillin, amoxicillin, amoxicillin/clavulanate, cefaclor, cefuroxime, cefotaxime, imipenem, ciprofloxacin, gemifloxacin, levofloxacin, erythromycin, clarithromycin, azithromycin, miocamycin, clindamycin and tetracycline. The insusceptibility rate (IR) to penicillin was 21.0% [10.8% intermediate (> or = 0.12-1 microgram/mL) and 10.2% high-level (> or = 2 micrograms/mL)], to cefotaxime 7.3% [3.5% intermediate (> or = 1 microgram/mL) and 3.8% high-level (> or = 2 micrograms/mL)], to imipenem 3.8% [3.8% intermediate (> or = 0.25-0.5 microgram/mL) and 0% high-level (> or = 1 microgram/mL)], to ciprofloxacin 11.2% [8.3% intermediate (2 micrograms/mL) and 3.9% high-level (> or = 4 micrograms/mL)], to erythromycin 30.3% [3.5% intermediate (0.5 microgram/mL) and 26.8% high-level (> or = 1 microgram/mL)] and to tetracycline 38.5% [0.9% intermediate (4 micrograms/mL) and 37.6% high-level (> or = 8 micrograms/mL)]. No decreased susceptibility was found for gemifloxacin (> or = 0.5 microgram/mL). This compound was the most active with MIC50, MIC90 and an IR of 0.015 microgram/mL, 0.03 microgram/mL and 0% respectively, followed by amoxicillin/clavulanate, amoxicillin and imipenem (MIC50, MIC90 and IR: 0.015 microgram/mL, 1 microgram/mL, 1.6%/0.015 microgram/mL, 1 microgram/mL, 1.9%/0.008 microgram/mL, 0.12 microgram/mL, 3.8% respectively). Compared to the 1999 surveillance, penicillin and tetracycline-insusceptibility increased with 4.9% and 15.6% respectively, while cefotaxime, erythromycin and ciprofloxacin insusceptibility decreased with 5.4%, 5.8% and 4.4% respectively. MICs of all beta-lactams rose with those of penicillin for penicillin-insusceptible isolates. Imipenem, cefotaxime, amoxicillin and amoxicillin/clavulanate were generally 4, 2, 1 and 1 doubling dilutions respectively more potent than penicillin on these isolates while ampicillin, cefuroxime and cefactor were generally 1, 2 and 4 dilutions respectively [table: see text] less potent. Most penicillin-insusceptible isolates remained fully susceptible to amoxicillin/clavulanate (92.4%), amoxicillin (90.9%) and imipenem (81.8%). Erythromycin-tetracycline insusceptibility was the most common resistance phenotype (14.3%). Three- and four-fold resistance was found in 12.4% and 1.6% respectively of the isolates. Most penicillin-insusceptible isolates were of capsular types 14 (22.7%), 23 (21.2%), 6 (18.2%), 9 (13.6%) and 19 (12.1%).

Study of the in vitro activity of amoxicillin/clavulanic acid and other beta-lactam antibiotics against Escherichia coli isolated from urine specimens.

A total of 205 serial, unduplicated urinary isolates of Escherichia coli was collected from June through August 1998 in 2 community and 3 hospital laboratories. By using the NCCLS broth microdilution technique, their in vitro susceptibility to ampicillin, amoxicillin/clavulanic acid, cefuroxime, cefuroxime axetil, ticarcillin/clavulanic acid and piperacillin/tazobactam was determined. One hundred and twenty isolates were from hospitalised patients, 85 from ambulatory, 129 community acquired and 76 nosocomial. Half of the nosocomial isolates were obtained from naturally produced and half from alternatively produced urine specimens. In general, the highest susceptibility rates, following NCCLS criteria, were found for piperacillin/tazobactam (93.2%) followed by cefuroxime (92.2%) and amoxicillin/clavulanic acid (82.9%). Ampicillin showed a clear bimodal distribution with a clear peak for the resistant population. The highest degree of ampicillin resistance was found in nosocomial isolates. Overall, ampicillin showed the lowest degree of susceptibility. Most of the ampicillin resistant isolates remained susceptible to piperacillin/tazobactam, cefuroxime and amoxicillin/clavulanic acid. In general, the community acquired isolates had higher susceptibility rates than the nosocomial isolates.

Comparative in vitro activity of temocillin and other antimicrobial agents against Enterobacteriaceae isolated from patients admitted to five Belgian hospitals.

Temocillin, a methoxy-derivative of the broad-spectrum penicillin, ticarcillin, has been introduced into clinical practice in Belgium in 1988. Since then, not many surveys of its in vitro activity have been published. This study addresses this issue in a prospective collection of 300 consecutive Gram-negative isolates originating from in-patients in five general hospitals throughout Belgium. In addition to temocillin, seven common antibiotics were tested: amoxicillin-clavulanate, piperacillin-tazobactam, cefotaxime, aztreonam, meropenem, ciprofloxacin and amikacin. Meropenem appeared to exhibit the best activity overall, whereas amoxicillin-clavulanate scored the worst. Cumulative MIC plot for two subsets of organisms are given: temocillin, meropenem and cefotaxime are the most active on E. coli and Klebsiella spp., while a significant percentage is resistant to ciprofloxacin and amoxicillin-clavulanate. In the group of inducible Enterobacteriaceae, temocillin, meropenem and amikacin are the most active drugs, while the activity of amoxicillin-clavulanate, piperacillin-tazobactam, cefotaxime and ciprofloxacin is largely decreased. Taking this well preserved in vitro activity of temocillin into account, and looking at its convenient pharmacokinetics and low cost of acquisition, this drug may prove a useful alternative in the treatment of severe nosocomial infections.

In vitro study on the antimicrobial activity of various antibiotics against clinical isolates of Streptococcus pneumoniae from Belgium collected during winter 1998-1999.

A total of 205 isolates of Streptococcus pneumoniae obtained from 10 different centres were included in this study. The susceptibilities to penicillin, ampicillin, amoxicillin, amoxicillin/clavulanic acid, cefaclor, cefuroxime, cefotaxime, imipenem, ciprofloxacin, gemifloxacin, grepafloxacin, levofloxacin, trovafloxacin, erythromycin, clarithromycin, miocamycin, clindamycin and tetracycline were determined by a microdilution technique following NCCLS recommendations. Decreased susceptibility to penicillin was 16.1% [6.8% intermediate (0.12-1 microgram/mL) and 9.3% high-level (> or = 2 micrograms/mL)], cefotaxime insusceptibility (> or = 1 microgram/mL) 12.7%, ciprofloxacine insusceptibility (> or = 2 micrograms/mL) 15.6% with 1.5% of high level resistance (> or = 4 micrograms/mL), erythromycin insusceptibility (> or = 0.5 microgram/mL) 36.1% and tetracycline insusceptibility (> or = 4 micrograms/mL) 22.9%. Decreased susceptibility to cefotaxime was found in 78.8% of the penicillin-insusceptible isolates. No decreased susceptibility was found for gemifloxacin (> or = 0.5 microgram/mL) and trovafloxacin (> or = 1 microgram/mL). Compared to the 1996-1997 surveillance, penicillin, cefotaxime and erythromycin insusceptibility rose by 3.8%, 5.2% and 5.0% respectively, while tetracycline insusceptibility decreased with 8.2%. MICs of all beta-lactams rose with those of penicillin for penicillin-insusceptible isolates. Amoxicillin +/- clavulanate, cefotaxime and imipenem were generally 1, 1 and 5 doubling dilutions respectively more potent than penicillin on these isolates. Penicillin, ampicillin and cefuroxime were equally active while cefaclor was generally 5 dilutions less potent. Most penicillin-insusceptible isolates remained fully susceptible to amoxicillin +/- clavulanate and imipenem. The penicillin-insusceptible isolates were 36.4%, 27.3% and 3.0% co-insusceptible to erythromycin, erythromycin plus tetracycline and tetracycline respectively. A subpopulation of 52 isolates obtained from children aged < or = 3 years was also studied. Compared to the other isolates we found a statistically significant increase in insusceptibility for penicillin, cefaclor, cefuroxime, erythromycin, clarithromycin and tetracycline while a significant decrease was found for ciprofloxacin.

Free kappa and lambda light chain levels in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases.

Free kappa and lambda light chains were assayed by particle-counting immunoassay in cerebrospinal fluid (CSF) from patients with various neurological disorders. Detection limits were 25 and 50 ng/ml, respectively. Values of free kappa chain were higher than 50 ng/ml (upper reference limit) in 155 of 191 (81%) multiple sclerosis (MS) patients, in 100 of 168 (60%) patients with central nervous system (CNS) infections but in 41 of 217 (19%) patients with other neurological disorders. Free kappa chains were also assayed in 273 matched sera. The mean concentration in the control group (1.58 micrograms/ml; SD: 0.41) did not differ significantly from those in MS sera (1.63 micrograms/ml; SD: 0.43). The free kappa chain index was increased in 86% of MS patients and in 40% of patients with CNS infections. Regarding free lambda chains, CSF values were higher than 240 ng/ml (upper reference limit) in most neurological disorders (50-100%). However, the use of a lambda chain index increased the specificity of the assay as this index was higher than the upper reference value in 86% of MS patients and in only 23% of patients with infectious diseases. In MS, high levels of free kappa and lambda indices correlated significantly (P less than 0.01) with either the presence of oligoclonal bands or a high IgG index. Local synthesis of free light chains is an additional marker of an ongoing immune response within the CNS, especially in MS.

Particle counting immunoassay of S100 protein in serum. Possible relevance in tumors and ischemic disorders of the central nervous system.

S100 protein (S100) was assayed by particle counting immunoassay in serum samples from 50 healthy individuals, 325 patients with various neurological disorders, and 20 patients with malignant melanoma. The detection limit for this protein was 0.3 microgram/L. We detected none in healthy individuals or in 50 patients with multiple sclerosis, 23 with dementia, or 20 with meningitis. S100 was detectable in serum of only a few patients with meningoradiculitis (2/20), peripheral neuropathy (2/30), encephalitis (1/14), Guillain-Barré syndrome (1/25), or AIDS (2/20). In contrast, we observed high concentrations in 29 of 75 patients with tumors of the central nervous system, especially in meningioma (6/9), glioblastoma (9/23), and neurinoma (5/5). Values for S100 were mainly abnormally high (greater than 0.3 microgram/L) in serum from patients with cerebrovascular disorders (43/48) or with metastases of melanoma (9/11).

Pregnancy-specific beta 1 glycoprotein (SP1) in the cerebrospinal fluid.

Pregnancy-specific beta 1 glycoprotein (SP1) was assayed by Particle Counting Assay in the cerebrospinal fluid (CSF) from 26 non-neurological patients, from 190 patients with various neurological disorders and from 84 patients with malignant hemopathies. With a sensitivity limit of 0.5 microgram/l, SP1 was undetectable in normal CSF. High levels were observed in CSF from one pregnant woman with herpetic encephalitis and from another woman with post-puerperal thrombophlebitis as a result of high serum concentrations and leakage of the blood-brain barrier. SP1 was detected at low levels in the CSF from 1 patient out of 5 with Creutzfeldt-Jakob disease and from a patient with Behçet's disease. Seven patients out of 84 with malignant hemopathies presented cerebral involvement; 3 of them had detectable SP1. However, SP1 was also detected in the CSF of 2 patients in apparently complete remission. The determination of SP1 in CSF appears to be of limited value in the diagnosis of neurological disorders and in the early detection of a cerebral localization of malignant hemopathies.

Pregnancy-specific beta 1-glycoprotein in serum in monoclonal gammopathies: relationship with serum beta 2-microglobulin, and cellular origin.

Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle-counting immunoassay in serum from 86 healthy blood donors and 236 patients with various types of gammopathy. A concentration of 1 microgram/L was taken as the upper normal limit. Abnormally high values were found in one of 10 patients with monoclonal gammopathy of undetermined significance, in 65% of 152 patients with multiple myeloma, in 84% of 64 patients with Waldenström's macroglobulinemia, and in seven of 10 patients with monoclonal gammopathies associated with other myeloproliferative disorders. In a study of 90 myeloma patients, the SP1 value correlated (p less than 0.001) with the concentration of beta 2-microglobulin in serum, a value which had been corrected for possible renal dysfunction, but not with the concentration of the monoclonal component. SP1 was detected by direct immunofluorescence in myeloma cells of bone-marrow smears from six of 10 patients with myelomatosis. These six patients had serum SP1 values greater than 1 microgram/L, whereas the four patients with fluorescence-negative myeloma cells had SP1 values less than 1 microgram/L.

Particle-counting immunoassay of a fetuin-like antigen in serum and cerebrospinal fluid.

A fetuin-like antigen was detected (smallest concentration detectable: 5 micrograms/L) by particle-counting immunoassay in 2% (13/641) of consecutive patients' sera but not in sera from 80 healthy blood donors, 40 neonates, or 40 pregnant women. The relation of the presence of detectable antigen to patients' diagnosis is not yet clear. However, in the group with cancer (154), it was found only in two of four patients with nephroblastoma and in three of five with tumors of tissue derived from the neurological crest: retinoblastoma (1/1), neuroblastoma (1/3), and medulloblastoma (1/1). Serum specimens from 422 patients with neurological disorders showed the antigen at a concentration greater than 5 micrograms/L in cases of neurosyphilis (5/11), peripheral neuropathy (12/38), Guillain-Barré syndrome (7/27), and multiple sclerosis (74/184). When we assayed 232 specimens of cerebrospinal fluid from the same neurological patients, we found the antigen in two cases of multiple sclerosis (6 and 15 micrograms/L) and in one case of Guillain-Barré syndrome (54 micrograms/L).

Prognostic value of concentration of pregnancy-specific beta 1-glycoprotein (SP1) in serum of patients with breast cancer.

Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle counting immunoassay in serum from 46 healthy female blood donors, 33 patients with benign mastopathy and 84 patients with breast cancer before operation and during follow-up. Values greater than 1 micrograms/1 were found more frequently with benign mastopathies (11/33) and in patients with breast cancer at stage 2 (20/48), 3 (4/9), and 4 (7/10) than in healthy female blood donors (3/46). The survival rate after 4 years was significantly lower in patients with SP1 level greater than 1 microgram/1 before tumor resection (52% vs. 87%). The difference remained significant when only patients in stage 2 were taken into account (57% vs. 85%). A highly significant (r = 0.64; N = 46) negative correlation was observed between the concentration of SP1 in serum and the concentration of estrogen receptor in the tumor. The longitudinal study of patients in stage 2 indicated that, of the 15 whose SP1 concentration fell below 1 microgram/1 after operation, 14 survived over 4 years whereas during the same period, 9 of the 10 patients whose SP1 value remained higher than 1 microgram/1 died.

Particle-counting immunoassay (PACIA) of pregnancy-specific beta 1-glycoprotein, a possible marker of various malignancies and Crohn's ileitis.

Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle-counting immunoassay (PACIA) with a sensitivity of 1 microgram/L. In serum from 50 men, the SP1 concentration was less than 1 microgram/L, whereas three of the specimens from 46 nonpregnant women had values exceeding 1 microgram/L. In 29% of 950 consecutive patients' sera, SP1 concentrations exceeded 1 microgram/L--in sarcoma (six of six), in malignant hemopathies (101/127, 80%) such as myeloma (20/26, 92%) and acute myeloblastic leukemia (23/27, 90%), and in various other types of cancer (11/19, 58%) except for bronchial epithelioma, which did not lead to any significant increase of SP1 in the five patients examined. The concentration of SP1 was also frequently increased in patients with Crohn's ileitis (28/43, 65%) but not in patients with other inflammatory disorders.