791 research outputs found
Calcium and magnesium in human toenails do not reflect bone mineral density
Nail mineral composition is influenced by several physiological and pathological processes. Potentially, nails could be used to monitor alterations in the level of incorporation of specific elements produced by nutritional abnormalities, disease states or chronic exposure to toxic agents. The purpose of this study was to investigate whether the calcium and magnesium content in nail clippings, as measured by instrumental neutron activation analysis (INAA), correlates with bone mineral density (BMD), as measured by quantitative microdensitometry (QMD), and therefore could be interesting as a screening instrument for osteoporosis. The study involved 220 women, who participated in a breast cancer screening project (the DOM-project) in Utrecht, the Netherlands. The correlations found between Ca and Mg measurements and bone mineral densities were very low (correlation coefficients ranging from 0.03 to 0.18). It is concluded that Ca and Mg measurements in nail clippings by INAA cannot be used for screening purposes in the prevention of osteoporosis
Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis
Streptococcus suis is one of the most important pathogens in pigs and is also an emerging zoonotic agent. After crossing the epithelial barrier, S. suis causes bacteraemia, resulting in meningitis, endocarditis and bronchopneumonia. Since the host environment seems to be an important regulatory component for virulence, we related expression of virulence determinants of S. suis to glucose availability during growth and to the sugar metabolism regulator catabolite control protein A (CcpA). We found that expression of the virulence-associated genes arcB, representing arcABC operon expression, cps2A, representing capsular locus expression, as well as sly, ofs, sao and epf, differed significantly between exponential and early stationary growth of a highly virulent serotype 2 strain. Deletion of ccpA altered the expression of the surface-associated virulence factors arcB, sao and eno, as well as the two currently proven virulence factors in pigs, ofs and cps2A, in early exponential growth. Global expression analysis using a cDNA expression array revealed 259 differentially expressed genes in early exponential growth, of which 141 were more highly expressed in the CcpA mutant strain 10¿ccpA and 118 were expressed to a lower extent. Interestingly, among the latter genes, 18 could be related to capsule and cell wall synthesis. Correspondingly, electron microscopy characterization of strain 10¿ccpA revealed a markedly reduced thickness of the capsule. This phenotype correlated with enhanced binding to porcine plasma proteins and a reduced resistance to killing by porcine neutrophils. Taken together, our data demonstrate that CcpA has a significant effect on the capsule synthesis and virulence properties of S. suis
Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972
BACKGROUND: Oligodendroglial tumors are chemosensitive, with two-thirds of
patients responding to PCV combination chemotherapy with procarbazine,
lomustine (CCNU) and vincristine. Temozolomide (TMZ), a new alkylating and
methylating agent has shown high response rates in recurrent anaplastic
astrocytoma. We investigated this drug in recurrent oligodendroglial
tumors (OD) and mixed oligoastrocytomas (OA) after prior PCV chemotherapy
and radiation therapy. PATIENTS AND METHODS: In a prospective
non-randomized multicenter phase II trial patients were treated with TMZ
150 mg/m(2) on days 1-5 in cycles of 28 days for 12 cycles. Eligible
patients had a recurrence after prior PCV chemotherapy, with measurable
and enhancing disease as shown by magnetic resonance imaging. Pathology
and all responses were centrally reviewed. RESULTS: Thirty-two eligible
patients were included. In four patients the pathology review did not
confirm the presence of an OD or OA. Twelve of 24 patients [50%, 95%
confidence interval (CI) 29% to 71%] evaluable for response to first-line
PCV chemotherapy had responded to PCV. Temozolomide was in general well
tolerated; the most frequent side-effects were hematological. One patient
discontinued treatment due to toxicity. In seven of 28 patients (25%, 95%
CI 11% to 45%) with histologically confirmed OD an objective response to
TMZ was observed. Median time to progression for responding patients was
8.0 months. After 6 and 12 months from the start of treatment, 29% and 11%
of patients, respectively, were still free from progression. CONCLUSIONS:
TMZ may be regarded as the preferred second-line treatment in OD after
failure of PCV chemotherapy. Further studies on TMZ in OD are indicated
Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients
Paraneoplastic cerebellar degeneration (PCD) is a heterogeneous group of
disorders characterized by subacute cerebellar ataxia, specific tumour
types and (often) associated antineuronal antibodies. Nine specific
antineuronal antibodies are associated with PCD. We examined the relative
frequency of the antineuronal antibodies associated with PCD and compared
the neurological symptoms and signs, associated tumours, disability and
survival between groups of PCD with different antibodies. Also, we
attempted to identify patient-, tumour- and treatment-related
characteristics associated with functional outcome and survival. In a
12-year period, we examined >5000 samples for the presence of antineuronal
antibodies. A total of 137 patients were identified with a paraneoplastic
neurological syndrome and high titre (> or =400) antineuronal antibodies.
Fifty (36%) of these patients had antibody-associated PCD, including 19
anti-Yo, 16 anti-Hu, seven anti-Tr, six anti-Ri and two anti-mGluR1.
Because of the low number, the anti-mGluR1 patients were excluded from the
statistical analysis. While 100% of patients with anti-Yo, anti-Tr and
anti-mGluR1 antibodies suffered PCD, 86% of anti-Ri and only 18% of
anti-Hu patients had PCD. All patients presented with subacute cerebellar
ataxia progressive over weeks to months and stabilized within 6 months.
The majority of patients in all antibody groups had both truncal and
appendicular ataxia. The frequency of nystagmus and dysarthria was lower
in anti-Ri patients (33 and 0%). Later in the course of the disease,
involvement of non-cerebellar structures occurred most frequently in
anti-Hu patients (94%). In 42 patients (84%), a tumour was detected. The
most commonly associated tumours were gynaecological and breast cancer
(anti-Yo and anti-Ri), lung cancer (anti-Hu) and Hodgkin's lymphoma
(anti-Tr and anti-mGluR1). In one anti-Hu patient, a suspect lung lesion
on CT scan disappeared while the PCD evolved. Seven patients improved by
at least 1 point on the Rankin scale, while 16 remained stable and 27
deteriorated. All seven patients that improved received antitumour
treatment for their underlying cancer, resulting in complete remission.
The functional outcome was best in the anti-Ri patients, with three out of
six improving neurologically and five were able to walk at the time of
last follow-up or death. Only four out of 19 anti-Yo and four out of 16
anti-Hu patients remained ambulatory. Also, survival from time of
diagnosis was significantly worse in the anti-Yo (median 13 months) and
anti-Hu (median 7 months) patients compared with anti-Tr (median >113
months) and anti-Ri (median >69 months). Patients receiving antitumour
treatment (with or without immunosuppressive therapy) lived significantly
longer [hazard ratio (HR) 0.3; 95% confidence interval (CI) 0.1-0.6; P =
0.004]. Patients > or =60 years old lived somewhat shorter from time of
diagnosis, although statistically not significant (HR 2.9; CI 1.0-8.5; P =
0.06)
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