Search PubMed⌕ Search

Biomedical subjects

G Rosati

Publications and source records attributed to G Rosati.

At least 37 records · Page 2Linked to original sources
PubMed2001

Which syringomyelia is truly associated with multiple sclerosis?

Necrosis of the spinal cord within multiple sclerosis (MS) lesions was suggested as a putative cause of syringomyelic cavity development in MS. A number of evidences suggest however that mechanisms other than necrosis are pathogenetically relevant for cavity formation, possibly depending on the atypical topographical distribution of the demyelinative lesion and on the increased cerebrospinal fluid pressure into the central canal below the compression. Not coincidentally, the hypothesis of post-necrotic and ex-vacuo mechanisms leading to cavitation derives from Japanese studies where MS is characterised by high tissue destructive capability and, besides its rarity, has many differences from the more common Western MS type and similarities with the acute disseminated encephalomyelitis (ADEM). Our opinion is that different MS types (Asian and Western) are accompanied by nonuniform mechanisms of syrinx formation and that the Asian MS type shares common, post-necrotic mechanisms with ADEM.

Cerebrospinal Fluid↗
PubMed2001

The prevalence of multiple sclerosis in the world: an update.

The systematic study of multiple sclerosis (MS) in populations, started in 1929 by Sydney Allison, now consists of over 400 publications dealing with the prevalence of MS throughout the world. However, any attempt to redefine the pattern of geographical differences in MS frequency remains as difficult as ever. The comparison of prevalence studies carried out in different areas and times is made difficult by the variability in surveyed population sizes, age structures, ethnic origins and composition, and the difficult quantification of numerators, especially regarding the recognition of benign and very early cases. Additionally, complete case ascertainment depends on access to medical care, local medical expertise, number of neurologists, accessibility and availability of new diagnostic procedures, the degree of public awareness about MS, and the investigators' zeal and resources. Critical examination of the more recent data on MS prevalence leads to some revisions of previously held concepts, the most interesting of which is the appreciation of the greater influence of genetic factors on disease acquisition. The rarity of MS among Samis, Turkmen, Uzbeks, Kazakhs, Kyrgyzis, native Siberians, North and South Amerindians, Chinese, Japanese, African blacks and New Zealand Maoris, as well as the high risk among Sardinians, Parsis and Palestinians, clearly indicate that the different susceptibilities of distinct racial and ethnic groups are an important determinant of the uneven geographic distribution of the disease. The updated distribution of MS in Europe, showing many exceptions to the previously described north-south gradient, requires more explanation than simply a prevalence-latitude relationship. Prevalence data imply that racial and ethnic differences are important in influencing the worldwide distribution of MS and that its geography must be interpreted in terms of the probable discontinuous distribution of genetic susceptibility alleles, which can however be modified by environment. Because the environmental and genetic determinants of geographic gradients are by no means mutually exclusive, the race versus place controversy is, to some extent, a useless and sterile debate.

Genetic Predisposition to Disease↗
PubMed2001

Multiple sclerosis prevalence among Sardinians: further evidence against the latitude gradient theory.

A descriptive epidemiological survey was extended to the whole province of Sassari, northern Sardinia between latitudes 40 degrees 30' N and 41 degrees N. Results showed a crude total prevalence rate of 144.4 per 100000 on prevalence day (31 December 1997), and an onset-adjusted prevalence rate of 149.7 per 100000. The total average annual incidence rate was 4.9 per 100000 for the whole time interval studied (1968-1997), having increased from 2.0 in 1968-1972 to 6.8 in the last quinquennium considered. A substantial improvement in MS case ascertainment due to the introduction of new diagnostic procedures might account for such rates in Sardinia as well as in other Italian regions. However, when comparing our data with those obtained in the province of Ferrara, in the same time frames (1968-1997), a nine-fold versus a five-fold increase of MS prevalence was detected in Ferrara and Sassari, respectively. MS incidence temporal trend also notably increased in Sassari, but remained substantially stable in Ferrara. The progressive shortening of the time interval between clinical onset and diagnosis, and the proportion of benign-mild MS cases, were similar in both studies, thus suggesting a similar diagnostic accuracy. In our opinion, the repeatedly assessed increase of MS frequency in our province, at least partially does represent an actual rise of MS risk among Sardinians, thus disproving the latitude gradient-based theory (i.e. prevalence rates correlate with geographical latitudes) and supporting the hypothesis of a "Sardinian focus" of MS in a genetically susceptible population.

Adult↗
PubMed2001

Immunogenetic heterogeneity of multiple sclerosis in Sardinia.

Multiple sclerosis (MS) predisposition is thought to be influenced by a complex, yet unclear interaction of genetic and environmental factors. Studying ethnically selected populations may reduce genetic and environmental heterogeneities and help clarify the underlying mechanisms of MS susceptibility. Sardinians kept a homogeneous genetic structure and have among the highest MS frequency rates worldwide. Interestingly, MS in Sardinia is linked to otherwise rare HLA alleles. In this light, recent findings from epidemiological and immunogenetic studies of Sardinian MS are presented. Results confirm that, likely due to significant genetic differences at a microgeographic level, even in this homogeneous population MS is immunogenetically heterogeneous and tends to preferentially cluster in some more archaic areas of the island.

Female↗
PubMed2001

Multiple sclerosis and multiple sclerosis-associated retrovirus in Sardinia.

The island of Sardinia has a high and increasing incidence of multiple sclerosis (MS). In a search for environmental factors that may account for this anomalously high incidence, we looked for evidence of multiple sclerosis-associated retrovirus (MSRV) that has previously been found in the plasma and cerebrospinal fluid of MS patients. We studied 25 MS patients and 25 matched healthy controls of ascertained Sardinian lineage. Blood samples were processed for extracellular RNA extraction. RNAs underwent reverse transcription/nested polymerase chain reaction (RT-PCR) with primers specific for MRSV-pol gene. We found a striking correlation between MSRV positivity and MS disease, but the virus was found also only in controls (100% and 12% respectively; Fisher's exact test, p<0.00001). It is unclear whether MSRV exerts any pathogenic role in MS. It is possible that this is simply an epiphenomenon, but even then, it may constitute a diagnostic marker.

Female↗
PubMed2001

Docetaxel and cisplatin in locally advanced or metastatic squamous-cell carcinoma of the head and neck: a phase II study of the Southern Italy Cooperative Oncology Group (SICOG).

BACKGROUND: Docetaxel is one of the most promising new drugs against squamous-cell carcinoma of the head and neck (SCCHN), while cisplatin is one of the most active single agents. A phase I study has shown the feasibility of the combination of the two drugs, and activity in SCCHN has been seen. PATIENTS AND METHODS: Patients with locally advanced, inoperable, or metastatic SCCHN, never pretreated with radiotherapy or chemotherapy, received three courses of docetaxel 75 mg/m2 and cisplatin 100 mg/m2, every three weeks. Thereafter, responsive metastatic patients received additional chemotherapy, while patients with locally advanced disease underwent radiation therapy. RESULTS: Forty-six patients (forty-five with locally advanced, one with metastatic disease) were entered into the study. Ten patients did not complete three courses of chemotherapy because of early death; one patient discontinued treatment after one course. Twenty-one objective responses were observed (46%, 95% confidence interval (CI): 31%-60%), including five complete responses (11%) and sixteen partial responses (35%). Following induction chemotherapy plus radiation therapy, 9 of 21 evaluable patients were rendered disease free, while 8 additional patients had a partial response. After a median follow-up of 18 months, the median duration of response was 12 months, (range 3-25+), and the median overall survival was 11 months. Six early deaths were considered possibly treatment-related (sepsis following grade 4 neutropenia in two cases, hypovolemic shock following severe diarrhea in four cases). Neutropenia was the most severe toxicity (grade 3-4 in 28 patients, median duration 4 days); diarrhea and vomiting were the most troublesome non-haematologic toxicities (grade 4 in 4 and 3 patients, respectively). CONCLUSIONS: The combination of docetaxel and cisplatin is active in SCCHN, but toxicity is substantial. This schedule does not appear to offer any advantage compared with conventional regimens.

Adult↗
PubMed2001

Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer.

PURPOSE: To identify the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of oxaliplatin (L-OHP) given on a weekly schedule including fixed doses of leucovorin (LV) and infusional 5-fluorouracil (5-FU), to define the toxicity profile of this regimen and to find preliminary evidence of its activity in pretreated patients with metastatic colorectal cancer (MCRC). PATIENTS AND METHODS: Twenty-one patients with progressive disease, treated with fluoropyrimidines and with histologically measurable MCRC entered into this phase I study. Fixed doses of LV (500 mg/m2) followed by a 48-hour 5-FU 2600 mg/m2 infusion (5-FU48h) were administered with escalating doses of L-OHP, starting from 60 mg/m2 and with stepwise increments of 5 mg/m2. No intra-patient dose escalation was allowed. Treatment was given once a week for four consecutive weeks, followed by a one-week rest period. RESULTS: Three dose levels were tested. The MTD was L-OHP 70 mg/m2 since two of the three patients showed dose-limiting diarrhea and the third developed neutropenia during the first cycle of chemotherapy. Most patients complained of mild peripheral sensitive neurotoxicity, which was related to the cumulative dose of L-OHP. Treatment delays were necessary for a total of 42 cases, but only in II of 42 after the pre-arranged 10% dose reduction of 5-FU (2300 mg/m2). Sixteen patients were evaluable for response: seven (33%; 95% confidence interval (CI): 14.6%-57.0%) were considered to show a major response (one complete), six showed a stable disease, and in addition progressive disease was observed in three patients. CONCLUSIONS: Our results show that L-OHP, LV and 5-FU can be administered safely and repetitively using a weekly schedule. Diarrhea and neutropenia are the DLT of this regimen. Its activity and its manageable toxicity profile deserve further evaluation in chemotherapy-naïve MCRC patients. The doses recommended for phase II trials are: L-OHP 65 mg/m2, LV 500 mg/m2 and 5-FU48h 2300 mg/m2 infusion given on a weekly-times-four schedule followed by a one-week rest period.

Aged↗
PubMed2001

Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk.

OBJECTIVES: To update prevalence and incidence rates of MS among Sardinians. MATERIALS AND METHODS: The present work is a "spider" kind of population based survey, conducted over the interval 1968-97, on patients with MS (Poser criteria) living in the province of Sassari, Northern Sardinia (454,904 population). RESULTS: A crude total prevalence rate of 144.4 per 100,000, an onset-adjusted prevalence rate of 149.7 per 100,000 and an average annual incidence rate of 8.2 for the period 1993-7 were found. CONCLUSION: Repeated epidemiological assessments of MS in Sardinia over decades have shown that the island is at high risk for MS. The present work highlights that MS incidence in Sardinia has been increasing over time. Although a substantial and widely spread improvement in MS case ascertainment can be postulated as the reason for such observations, a comparison between our data and those recently reported from a more industrialized province in Northern Italy seems to prove an at least partially real increase in MS risk among Sardinians and favours the hypothesis of a MS "Sardinian focus" as related to its latitude.

Adolescent↗
PubMed2001

Epileptic seizures after treatment with thiocolchicoside.

PURPOSE: To report the occurrence of epileptic seizures in humans, closely related to the use of the centrally acting muscle relaxant thiocolchicoside. METHODS: Description of three case histories. RESULTS: Two patients, affected with complex-partial seizures, sometimes secondarily generalized, receiving antiepileptic therapy, were seizure free for 7 and 9 years, respectively. They had the reappearance of tonic-clonic seizures few days after the continued use of thiocolchicoside, at a cumulative dose of the drug of 52 mg and 76 mg, respectively. The third patient was brain damaged and without a history of seizures. He had a sudden, convulsive seizure a few minutes after 4 mg intramuscular thiocolchicoside. CONCLUSIONS: Our case histories indicate that thiocolchicoside has a powerful epileptogenic activity. This drug should be avoided in patients with epilepsy or acute brain injury and possible disruption of the blood-brain barrier.

Adult↗
PubMed2001

Chlamydia pneumoniae in the cerebrospinal fluid of patients with multiple sclerosis and neurological controls.

Chlamydia pneumoniae infection is a common event in neurological patients and recovery of C. pneumoniae DNA in the cerebrospinal fluids (CSF) of multiple sclerosis (MS) patients could represent an epiphenomenon. We assessed the relevance of C. pneumoniae infection in 62 CSF samples from 32 MS patients and 30 neurological controls by means of PCR, immunofluorescence microscopy, enzyme-linked fluorescence and antibody detection. Multiple sclerosis (9.3%) and neurological controls (13.3) had similar percentage of anti-C. pneumoniae antibodies. However, C. pneumoniae DNA was only detectable in MS patients' CSF (9.3%). Our data support the hypothesis that C. pneumoniae persistence in some MS patients may be the result of an impaired clearance within the central nervous system.

Adult↗
PubMed2001

Expression profile of epidermal differentiation complex genes in normal and anal cancer cells.

Anal cancer originates from a peculiar histological region and provides a useful model for investigating alterations in proliferation and/or differentiation of neoplastic keratinocytes. Epidermal differentiation complex (EDC) genes, which form one of the major gene clusters in the human genome, are involved in the terminal differentiation of epithelial cells and in many instances have been implicated in epithelial tumours. We constructed a DNA macroarray capable of characterising the expression profiles of the entire EDC gene complex in normal mucosa and anal cancer biopsies of seven unrelated patients. Brain tissue and cultured keratinocytes were used as controls. All anal cancer samples showed expression profiles in which none of the EDC genes was silent, as evaluated by phosphor-imager analysis. Variance analysis showed significantly lower expression of SPRR2 with respect to SPRR1 or SPRR3, and significantly higher expression of S100A8 than of other S100A subfamily members. At hierarchical clustering analysis, the four basaloid anal cancer cases conglomerated in the top five positions. The macroarray method used by us provides the first demonstration of the expression profile of the EDC gene family in anal cancer, and is capable of producing significant information on the subgrouping of epithelial tumours such as anal cancer.

Adult↗
PubMed2000

The increasing incidence and prevalence of MS in a Sardinian province.

OBJECTIVE: To verify incidence rates and their temporal trend in a homogeneous, ethnically, and genetically distinct population of central Sardinia (the Nuoro province). BACKGROUND: Intensive epidemiologic studies carried out in Sardinia since the 1970s have suggested that the prevalence and incidence of MS are much higher in this Mediterranean island compared with those found on mainland Italy. METHODS: The study area had a population of approximately 274, 000 people in the 1991 census. The authors adopted a complete enumerative approach by reviewing all possible sources of case collection available in the investigative area. RESULTS: Based on 469 MS patients, the mean annual incidence for 1955 to 1995 was 4.18 per 100,000 (or 4.3 per 100,000 if age- and sex-adjusted to the European population). The incidence, averaging 1.95 per 100,000 during 1955 to 1959, rose progressively over time, reaching rates of 6.6 in the quinquiennium 1985 to 1989 and 6.4 per 100,000 in 1990 to 1995. On December 31, 1994, the crude prevalence, based on 415 MS patients alive in the study area, was 151.9 per 100,000 (156.6 if adjusted to the European population). CONCLUSION: These incidence and prevalence rates are the highest to date that have been estimated for a large community in southern Europe, and they constitute some of the highest rates in the world. Based on other surveys, these results reinforce the position of Sardinia as a higher and rising prevalence area for MS compared with other Mediterranean populations. Genetic and social-historic data strengthen the hypothesis of the environmental role and genetic factors among Sardinians in determining the notable difference in MS frequency between Sardinians and other Mediterraneans.

Adolescent↗
PubMed2000

Defensive extrusive ectosymbionts of Euplotidium (Ciliophora) that contain microtubule-like structures are bacteria related to Verrucomicrobia.

Epixenosomes, ectosymbionts on hypotrich ciliates (genus Euplotidium) defend their host against the ciliate predator Litonotus lamella. Although here only Euplotidium itoi and Euplotidium arenarium from tide pools along a rocky shore near Leghorn (Ligurian sea) were studied in detail, these epibionts are certainly present on specimens of E. itoi and on other Euplotidium species in similar north coastal habitats. The complex life history of epixenosomes has two main stages. In stage I, cells with typical prokaryotic structure divide by binary fission. Stage II cells show complex organization with different cytoplasmic compartments where an extrusive apparatus within a proteinaceous matrix, although not membrane-bounded, differs from the remaining cytoplasm. The ejection process is involved in defense; extrusive apparatus is surrounded by a basket consisting of bundles of tubules. These tubules, 22 +/- 3 nm in diameter, delimited by a wall made up of globular structures, are sensitive to inhibitor of tubulin polymerization (nocodazole/4 degrees C temperature) and react positively with different antitubulin antibodies, two of which are monoclonal. The prokaryotic vs. eukaryotic nature of epixenosomes was resolved by comparative sequence analysis of amplified small subunit rRNA genes and in situ hybridization with fluorescently labeled rRNA-targeted polynucleotide probes. These unique ectosymbionts are phylogenetically related to Verrucomicrobia. Epixenosomes represent marine symbionts in this recently discovered division of the Bacteria.

Animals↗
PubMed2000

Risperidone, neuroleptic malignant syndrome and probable dementia with Lewy bodies.

1. Conflicting reports are available regarding the sensitivity of patients with Dementia with Lewy bodies (DLB) to risperidone. 2. The authors studied a rare familial case of probable DLB, who developed a documented episode of neuroleptic malignant syndrome (NMS) following the exposure to risperidone. Previously, the patient had had an episode of NMS on trifluoperazine. 3. The discontinuance of risperidone, in combination with a mild increase of dopaminergic therapy, led to a complete recovery in few days. 4. In patients with DLB, a continued vigilance for extrapyramidal side effects, including NMS, would be advisable during the use of risperidone.

Antipsychotic Agents↗
PubMed2000

Contemporaneous bilateral forearm triceps metastases from adenocarcinoma of the lung.

Haematogenous skeletal muscle metastases from non-small-cell lung cancer (NSCLC) are rare, and are even more uncommonly observed bilaterally. Usually, NSCLC metastasizes to the liver, adrenal glands, lung, bone, central nervous system and kidney. We report a case of a long-surviving patient with contemporaneous histologically proven bilateral muscle metastases in the right and left forearm triceps, from adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed2000

Expression analysis and mutational screening of the epithelium-specific ets gene-1 (ESE-1) in patients with squamous anal cancer.

To investigate whether ESE-1 gene abnormalities are involved in alterations of epithelial cell differentiation in squamous anal cancer ESE-1 expression and structure were screened in six patients by reverse transcriptase-polymerase chain reaction (RT-PCR) and automated sequence analysis. The complete cDNA of isoform ESE-1b was always expressed and correctly spliced, with single nucleotide polymorphism being observed in two cases. Presence of ESE-1b point mutations was excluded. Expression of SPRR2A and ENDOA/CK8, two epithelium-specific ESE-1 target genes, were revealed by RT-PCR in all cases. This first report of expression of ESE-1, and of SPRR2A and ENDOA/CK8 (both related to terminal differentiation in different types of epithelia lining) in anal cancer excludes the hypothesis that these genes influenced carcinogenesis in our patients. Despite selecting of patients without clinical evidence of HPV infection, PCR consistently revealed HPV-16 DNA, highlighting the importance of HPV infection in anal cancer.

Adult↗