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Biomedical subjects

A Pace

Publications and source records attributed to A Pace.

At least 19 recordsLinked to original sources
PubMed2006

Early post-operative MRI: correlation with progression-free survival and overall survival time in malignant gliomas.

Forty-seven patients with Glioblastoma (42) and Anaplastic Astrocytoma (5) were studied with MR 24 hrs after surgery. In order to evaluate the role of early MR in defining the extent of surgical resection and its relation with the prognosis of malignant glioma patients, three categories of surgical resection were considered: gross total, sub-total and partial resection. The results were correlated with progression-free survival (PFS) and overall survival (ST). As demonstrated by early-MR, gross total resection was performed in 17 patients, sub-total and partial resection in 19 and 11 patients, respectively. The PFS was 6 months in gross total resection, 6 and 3 months in sub-total and in partial resection, respectively. The median survival time was 16 months in total resection patients, 13 months and 7 months in sub-total resection and partial resection patients, respectively. The study confirms that early-MR has to be considered an accurate technique for monitoring the extension of malignant glioma surgical resection and shows a good correlation between early-MR findings, PFS and ST.

Adult↗
PubMed2005

Choroid plexus carcinoma in the adult: is there a role for chemotherapy?

Choroid plexus carcinoma is a rare primary brain neoplasm arising from epithelial differentiated tissue, originating from the choroids plexus of the ventricles and, in 90% of the cases, in the lateral and fourth ventricles. This neoplasm is seen mainly in children and reported infrequently in adults. The treatment of choroid plexus carcinoma is based on scarce evidence in literature. We report a rare case of an adult woman affected by a choroid plexus tumour and a discussion on the therapeutic management of this uncommon adult malignancy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Rheumatology patient preferences for timing and location of out-patient clinics.

OBJECTIVES: To determine the preferences of rheumatology patients for the time and location of their out-patient appointments. METHODS: All patients attending the rheumatology out-patient services at Dudley Group of Hospitals NHS Trust over a 2-week period were asked to complete a purpose-designed, scannable, previously piloted, self-administered questionnaire. RESULTS: Four hundred and nineteen patients completed questionnaires (response rate 87%). Age ranged from 16 to 92 yr; 38% of responders were over 65 yr, 72% were female, 57% had an inflammatory arthritis, 20% had a connective tissue disease, 8% had degenerative joint disease and 15% had another diagnosis; 29% were employed, 51% retired and 20% unemployed. Fewer than 1% of patients would like to be seen at community general practice centres (99.3% would prefer a hospital site). Proximity to their home was the main determinant of hospital choice. Monday was the most popular day for appointments, and days from Tuesday to Friday received equal rankings. Only 0.5% of patients would choose a weekend clinic. Fifty-eight per cent of patients would prefer morning appointments, 24% afternoon appointments and 2% evening appointments; 16% did not mind. Only being employed predicted out-of-hours preference. CONCLUSIONS: In this predominantly suburban, industrialized area, rheumatology out-patients prefer to be seen in the hospital rather than primary care environment, ideally close to their home, with appointments in the morning and on a weekday. These results may be generalizable to other districts and other chronic disease states, but we suggest that similar surveys become part of routine service provision and inform current and future planning.

Adolescent↗
PubMed2003

The prevalence of patients with rheumatoid arthritis in the West Midlands fulfilling the BSR criteria for anti-tumour necrosis factor therapy: an out-patient study.

OBJECTIVES: There are currently two anti-tumour necrosis factor (anti-TNF) therapies licensed for treatment of rheumatoid arthritis (RA). A British Society for Rheumatology (BSR) working party defined criteria for patients that would be suitable for such treatment. The aim of this study was to determine the prevalence of these patients attending rheumatology out-patient departments across the West Midlands. METHODS: Data were collected over a 2-week period in adult out-patient departments of 12 centres. A questionnaire was completed at each patient review. Disease activity scores (DAS-28) were recorded for those who had failed methotrexate treatment and at least one other disease-modifying anti-rheumatic drug (DMARD) in the absence of contraindications to anti-TNF therapy. Information was also collected on the number of DMARDs failed and the use of steroid therapy. RESULTS: A total of 1441 patients with RA were assessed; 177 (12.3%) patients had failed methotrexate and at least one other DMARD. Of these, 19 had contraindications to the use of anti-TNF therapy. In the remaining 158 patients (11%), 80 (5.6%) had a DAS-28 score of >5.1, thus fulfilling BSR criteria for use of anti-TNF therapy. Those with a DAS-28 score of < or = 5.1 were significantly more likely to have been taking steroids compared with those with a DAS-28 score >5.1 (68.2 and 49.3%, respectively, P=0.024). CONCLUSIONS: Of patients with RA attending adult rheumatology out-patient clinics in the West Midlands, 5.6% would meet BSR criteria for use of anti-TNF therapy. Eligibility may be affected by steroid use.

Adult↗
PubMed2003

Trauma care systems in Italy.

In this article we analyse the Italian Trauma System, stressing what has been modified over the last decade, in order to provide a more adequate and safe pre-hospital care, as well as a more efficient in-hospital treatment. We describe how the 118 operative exchange is organised, the most important educational courses for the health personnel and the new emergency/urgency structures called DEA.

Ambulances↗
PubMed2003

Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene.

We describe a Sicilian family presenting a recessive form of hypercholesterolemia harboring a mutation of the autosomal recessive hypercholesterolemia (ARH) gene. In two of the three sibs, a 26-year-old male and a 22-year-old female, a severe hypercholesterolemia was diagnosed with very high levels of plasma cholesterol (15.9 and 12.2 mmol/l, respectively); tendon xanthomatas and xanthelasms were present and in the male proband was documented a diffuse coronary atherosclerotic disease with a rapid and fatal progression. Both the parents had normal or slightly increased levels of plasma cholesterol. All causes of secondary hypercholesterolemia were ruled out as well as an involvement of the LDL receptor or apoB genes. Beta-Sitosterol plasma levels were in the normal range. Cultured fibroblasts from skin biopsy from parents and the two probands displayed a normal ability to bind and degrade 125I-LDL. Direct sequencing of ARH gene demonstrated the presence of a 432insA mutation in homozygosis in the two probands; parents were heterozygotes for the same mutation. This mutation is the first report of a mutation of the ARH gene responsible for recessive forms of hypercholesterolemia in Sicily.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Low-density-lipoprotein peak particle size in a Mediterranean population.

BACKGROUND: The predominance of small, dense low-density lipoprotein (LDL) particles ('LDL phenotype B') has been associated with a three-fold increased risk of myocardial infarction, but the feasibility of the identification of small, dense LDL as independent predictors of coronary artery disease risk in population studies remains questioned. Design We evaluated the LDL peak particle size and its relation with other established risk factors for coronary heart disease in a group of 156 randomized subjects living on the Mediterranean island of Ustica (71 males and 85 women, range of age 20-69 years), representing approximately 30% of the total population. RESULTS: The prevalence of LDL phenotype B subjects was low (approximately 15% in both men and women) and there was a clear trend for both genders in reducing the LDL peak particle size with age. Moreover, LDL phenotype B subjects had higher BMI values, prevalence of diabetes and plasma triglyceride (TG) levels and lower plasma HDL-C concentrations in comparison with LDL phenotype A individuals; in a multivariate analysis, plasma TG levels were the only variable independently associated with LDL peak particle size. CONCLUSIONS: In this population, which appears to be somewhat protected by premature coronary artery disease, a low prevalence of the LDL pattern B was found in both men and women, and plasma TG could have a key role in regulating the LDL peak particle size. The follow up, still ongoing, will provide useful information on the predictive role of LDL peak particle size on cardiovascular risk, at least in a low-risk population.

Adult↗
PubMed2003

Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response.

BACKGROUND: The optimal treatment for low-grade glioma (LGG) is still controversial. Recent data indicate a potential influence of chemotherapy on the natural evolution of these tumors, allowing for the deferral of more aggressive therapies. PATIENTS AND METHODS: Forty-three patients affected with LGG (29 astrocytoma, four oligodendroglioma and 10 mixed oligo-astrocytoma) were treated with temozolomide (TMZ) at the time of documented clinical and radiological progression. McDonald's response criteria were utilized to evaluate TMZ activity. Thirty patients (69.7%) had previously received radiotherapy; 16 (37.2%) had received prior chemotherapy. Clinical benefit was evaluated measuring seizure control, reduction in steroid dose and modification of Karnofsky performance status and Barthel index. Quality of life was assessed with the QLQ-C30 questionnaire. RESULTS: We observed a complete response in four patients, 16 partial responses, 17 stable disease (with four minor response) and six progressive disease. Median duration of response was 10 months [95% confidence interval (CI) 8-12], with a 76% rate of progression free survival (PFS) at 6 months, and a 39% rate of PFS at 12 months. A relevant clinical benefit was observed particularly in patients presenting epilepsy. CONCLUSIONS: The high response rate of 47% (95% CI 31% to 61%) confirms that TMZ chemotherapy is a valid option in the treatment of progressive LGG. The present preliminary results seem interesting and warrant further evaluation of TMZ clinical activity in a larger series of progressive LGG.

Administration, Oral↗
PubMed2003

Lithium fluoride as a novel X-ray image detector for biological mu-world capture.

X-ray microradiographs of small biological objects, such as animals and plant materials at micrometric resolution, are currently performed by various methods, all of which are limited by the resolution or the dynamic range of the image detectors. Here a novel X-ray image detector is discussed, in which the previous limitations have been overcome. A film of lithium fluoride salt is used as a detector, in which the stored biological image is read by observing the optically stimulated visible luminescence of the active color centers, efficiently produced by the X-rays.

Animals↗
PubMed2003

Demyelinating disease in monoclonal gammopathy of undetermined significance.

We describe herein the case of a 57 year old man who, over the last five years, has presented ataxic and spastic gait on the right side, a reduction in fine motor movement of the fingers mainly on the right side, superficial right side brachiocrural hypoesthesia and a marked dysarthria associated with internuclear ophthalmoplegia. The neurological picture, after an initial progressive worsening which lasted some months, remained relatively stable over the years. Repeated magnetic resonance imaging (MRI) of the brain and spinal cord documented the presence of demyelinating plaques spread in the white matter of the periventricular region and the semioval centres, and a right side paramedian plaque at the C4-C5 level, none of which were in the active phase. Oligoclonal bands were revealed in the cerebrospinal fluid (CSF). Monoclonal IgM/lambda gammopathy with anti-myelin and anti-nucleo reactivity, found with serum immunofixation, were confirmed several times in successive annual controls, not associated to myeloproliferative pathology. The lack of progression in the clinical picture would seem to contradict the diagnosis of late Multiple Sclerosis. The presence of antibody activity against the myelin might support the hypothesis of a pathogenetic role of the immunoglobulins at the onset of the demyelinating disease in this patient. However, in the end, there is the possibility of casual association with a poorly functioning immune system connected to age.

Brain↗
PubMed2001

A pilot study on the relation between cisplatin neuropathy and vitamin E.

Peripheral sensory neuropathy is the main non-hematological side-effect related to cisplatin chemotherapy. The strong similarity between clinical and neuropathological aspects in peripheral neuropathy induced by cisplatin and neurologic syndromes due to vitamin E deficiency, prompted us to investigate the relationship between cisplatin neuropathy and plasmatic level of vitamin E (alpha-tocopherol). We measured vitamin E in the plasma of 5 patients (Group 1) which developed severe neurotoxicity after cisplatin treatment and in another group of 5 patients (Group 2) we analyzed the plasmatic level of vitamin E before and after 2 or 4 cycles of cisplatin treatment. The results showed that the patients of group 1 presented low plasmatic levels of vitamin E and that the patients of group 2 presented significantly lower levels of vitamin E after 2 or 4 cycles of cisplatin than before treatment. Our preliminary data suggest that an inadequate amount of the antioxidant vitamin E due to cisplatin treatment could be responsible of the peripheral nerve damage induced by free-radicals. Given the lack of toxicity of vitamin E, we need to systematically assess the possible neuroprotective role of vitamin E supplementation in patients treated with cisplatin chemotherapy.

Adult↗
PubMed2000

Laparoscopic cholecystectomy and the Peter Pan syndrome.

We report the case of a patient who experienced hemobilia a few weeks after undergoing laparoscopic cholecystectomy (LC). This condition was due to the rupture of a pseudo-aneurysm of the right hepatic artery in the common bile duct, probably caused by a clip erroneously fired during LC on the lateral right wall of the vessel. It also caused the formation of multiple liver abscesses and the onset of sepsis. This life-threatening complication led to melena, fever, epigastric pain, pancreatitis, liver dysfunction, and severe anemia, requiring urgent hospitalization and operation. In the operating theater, the fistula was closed, the liver abscesses drained, and a Kehr tube inserted. Thereafter, the patient's general condition improved, and she is now well. LC is often considered to be the gold standard for the management of symptomatic cholelithiasis. However, recent data have undermined that opinion. The apparent advantages offered by LC in the short term (less pain, speedier recovery, shorter hospital stay, and lower costs) have been overwhelmed by the complications that occur during long-term follow-up. When the late downward trend in the bile duct and the vascular injury rate are taken into consideration, the learning curve is prolonged. Therefore, LC should be regarded as the surgical equivalent of a modern Peter Pan-i.e., it is like a young adult who should make definitive steps toward becoming an adult but does not succeed in doing so. We report the case of a patient who experienced hemobilia a few weeks after undergoing laparoscopic cholecystectomy. Based on the facts in this case, we argue that the endoscopic procedure still needs to be perfected and cannot yet be considered the gold standard for selected cases of gallstone disease.

Biliary Fistula↗
PubMed2000

Weekly schedule of vinorelbine in pretreated breast cancer patients.

PURPOSE: In this phase II study, we explored tolerability and activity of vinorelbine administered according to a dose-dense weekly schedule with hematopoietic growth factor support in pretreated, advanced breast cancer patients. PATIENTS AND METHODS: From January 1994 to March 1996, 40 patients with metastatic breast cancer, pretreated with at least one prior anthracycline-containing regimen, were entered into the study. PATIENT CHARACTERISTICS: median age 53 years (range 32-70); ECOG performance status 0-1: 34 patients, 2: 6 patients; dominant visceral metastatic disease: 15 patients, dominant non-visceral: 25; anthracycline-refractory/resistant: 2 patients, sensitive: 38 patients. Six patients were treated as first-line therapy for metastatic disease and 34 in second- or subsequent lines. All patients received vinorelbine at the dose of 25 mg/m2/week as a short intravenous infusion, together with routine antiemetic medication. Granulocyte-colony stimulating factor (Lenograstim) at the dose of 150 microg/m2 subcutaneously on day 3 was included in the treatment schedule. RESULTS: The median number of treatment weeks was 23 (range: 4-24), with a delivered dose-intensity (DDI) of 23.8 mg/m2/week (range: 18.7-25, 95.2% of projected dose-intensity). Toxicity was mild, with non-complicated neutropenia being the main toxicity observed (grade 3-4 in 25% of the patients but only 2% of treatment weeks). Overall response rate was 52.5%, with complete responses in 12.5% of patients. Median duration of the response and median time to progression were 10 and 9 months, respectively. Median overall survival was 19 months. CONCLUSION: Dose-dense weekly vinorelbine is safe and effective with minimal toxicity in pretreated advanced breast cancer patients.

Adjuvants, Immunologic↗
PubMed2000

Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor.

The aim of our study was to explore whether nerve growth factor (NGF) plays any role in the development of peripheral neuropathy induced by anticancer treatment. We measured the circulating NGF levels in 23 cancer patients before and after chemotherapy. We evaluated whether the development of peripheral neurotoxicity was associated with changes in basal NGF concentrations in patients studied with a comprehensive neurological and neurophysiological examination. The results of these studies showed that the circulating levels of NGF, which are about 20 pg/ml in plasma of controls, decrease during chemotherapy and in some cases completely disappeared after prolonged treatment with antitumor agents. The decrease in NGF levels seems to be correlated with the severity of neurotoxicity. These results clearly suggest that NGF might become a useful agent to prevent neuropathies induced by antineoplastic drugs and restore peripheral nerve dysfunction induced by these pharmacological compounds.

Aged↗
PubMed1999

Phorbol ester-induced disruption of the CD4-Lck complex occurs within a detergent-resistant microdomain of the plasma membrane. Involvement of the translocation of activated protein kinase C isoforms.

Recent studies have highlighted the existence of discrete microdomains at the cell surface that are distinct from caveolae. The function of these microdomains remains unknown. However, recent evidence suggests that they may participate in a subset of transmembrane signaling events. In hematopoietic cells, these low density Triton-insoluble (LDTI) microdomains (also called caveolae-related domains) are dramatically enriched in signaling molecules, such as cell surface receptors (CD4 and CD55), Src family tyrosine kinases (Lyn, Lck, Hck, and Fyn), heterotrimeric G proteins, and gangliosides (GM1 and GM3). Human T lymphocytes have become a well established model system for studying the process of phorbol ester-induced down-regulation of CD4. Here, we present evidence that phorbol 12-myristate 13-acetate (PMA)-induced down-regulation of the cell surface pool of CD4 occurs within the LDTI microdomains of T cells. Localization of CD4 in LDTI microdomains was confirmed by immunoelectron microscopy. PMA-induced disruption of the CD4-Lck complex was rapid (within 5 min), and this disruption occurred within LDTI microdomains. Because PMA is an activator of protein kinase C (PKC), we next evaluated the possible roles of different PKC isoforms in this process. Our results indicate that PMA induced the rapid translocation of cytosolic PKCs to LDTI microdomains. We identified PKCalpha as the major isoform involved in this translocation event. Taken together, our results support the hypothesis that LDTI microdomains represent a functionally important plasma membrane compartment in T cells.

Biological Transport↗
PubMed1999

Cyclooxygenase-independent induction of p21WAF-1/cip1, apoptosis and differentiation by L-745,337, a selective PGH synthase-2 inhibitor, and salicylate in HT-29 cells.

In order to dissect out cyclooxygenase-dependent from cyclooxygenase-independent mechanisms in the antiproliferative effects of selective prostaglandin H synthase (PGHS)-2 inhibitors, we compared the effects of L-745,337 (a highly selective PGHS-2 inhibitor) with sodium salicylate (a weak PGHS inhibitor) on prostanoid production, induction of the cyclin-dependent kinase inhibitor p21WAF-1/cip1, mutant p53 (m273-p53) levels, apoptosis and differentiation in human colon adenocarcinoma HT-29 cells. L-745,337 dose-dependently suppressed the cyclooxygenase activity of HT-29 cells (IC50: 0.24 microM). Four-day treatment with L-745,337 caused a concentration-dependent inhibition of cell growth (IC50: 0.9 mM) associated with the induction of p21WAF-1/cip1 and an increase in the proportion of apoptotic nuclei (EC50: 0.1 and 0.34 mM, respectively) while reducing the levels of m273-p53 (IC50: 0.2 mM). Sodium salicylate, at the concentration of 10 mM that did not affect prostanoid formation, caused a 60% reduction of cell growth associated with a 3-fold induction of p21WAF-1/cip1 and a 60% increase in the proportion of apoptotic nuclei. Ultrastructural analysis showed that L-745,337 (0.5 mM) and sodium salicylate (10 mM) caused the induction of a differentiated phenotype. We conclude that high concentrations of L-745,337 and sodium salicylate inhibit colon cancer cell growth by a mechanism unrelated to cyclooxygenase inhibition that may involve p53-independent induction of the tumor suppressor p21WAF-1/cip1.

Journal Article↗