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M Coelho

Publications and source records attributed to M Coelho.

At least 19 recordsLinked to original sources
PubMed2005

The European Multiple System Atrophy-Study Group (EMSA-SG).

Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging (MRI and DWI, respectively). Results. 412 patients have been recruited into the Registry so far. Probable MSA-P was the most common diagnosis (49% of cases). 507 patients donated DNA for research. 131 patients have been recruited into the NHS. There was a rapid deterioration of the motor disorder (in particular akinesia) by 26.1% of the UMSARS II, and - to a lesser degree - of activities of daily living by 16.8% of the UMSARS I in relation to the respective baseline scores. Motor progression was associated with low motor or global disability as well as low akinesia or cerebellar subscores at baseline. Mental function did not deteriorate during this short follow up period. Conclusion. For the first time, prospective data concerning disease progression are available. Such data about the natural history and prognosis of MSA as well as surrogate markers of disease process allow planning and implementation of multi-centre phase II/III neuroprotective intervention trials within the next years more effectively. Indeed, a trial on growth hormone in MSA has just been completed, and another on minocycline will be completed by the end of this year.

Animals↗
PubMed2005

Botulinum toxin type A therapy for cervical dystonia.

BACKGROUND: Cervical dystonia is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. In recent years, Botulinum toxin Type A (BtA) has become the first line therapy. However its true efficacy, in particular the potential effect size, is still unclear. OBJECTIVES: To determine whether botulinum toxin (BtA) is an effective and safe treatment for cervical dystonia. SEARCH STRATEGY: We searched the Cochrane Movement Disorders Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2003, MEDLINE (1977 to June 2003), EMBASE (1977 to June 2003) and reference lists of articles. We also contacted drug manufacturers and researchers in the field. SELECTION CRITERIA: Randomised studies comparing BtA with placebo in adults with cervical dystonia. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: We found thirteen high quality eligible studies. They were short term (6 to 16 weeks). Eight trials, enrolling 361 patients, used the BtA formulation Botox(r) and five, enrolling 319 patients, used the BtA formulation Dysport. The dose and technique of administration varied significantly between studies.Meta-analysis showed statistically and clinically significant improvements on objective rating scales: (Peto OR 4.31; 95% confidence interval (CI) 2.68 to 6.94) and subjective rating scales (Peto OR 6.58; 95% CI 4.55 to 9.54); and for pain relief in subjective scales (Peto OR 11.92; 95% CI 6.32 to 22.5). However, for many of the outcomes, we could use data from only a few studies. Only adverse events clearly associated with the mechanism of action of BtA were more frequent in the treatment group. These included neck weakness, dysphagia, dry mouth/sore throat and voice changes/hoarseness. Sub-group and sensitivity analyses showed a clear dose-response relationship for subjective and objective benefit and for frequency and severity of adverse events. Indirect comparisons between trials that used Dysport against placebo and trials that used Botox against placebo showed no significant differences between Dysport and Botox in terms of benefits or adverse events. AUTHORS' CONCLUSIONS: A single injection cycle of BtA is effective and safe for treating cervical dystonia. Enriched trials (using patients previously treated with BtA), suggest that further injection cycles continue to work for most patients.

Botulinum Toxins, Type A↗
PubMed2005

Botulinum toxin type A versus anticholinergics for cervical dystonia.

BACKGROUND: Cervical dystonia is the most common form of focal dystonia. It is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. Most cases are idiopathic and generally cervical dystonia is a life-long disorder. Botulinum toxin Type A (BtA) is now the first line therapy. Before BtA, anticholinergics were the most widely accepted treatment, so it is important to understand how these two treatments compare. OBJECTIVES: To compare the clinical efficacy and safety of BtA versus anticholinergic drugs in the treatment of cervical dystonia. SEARCH STRATEGY: We searched the Cochrane Movement Disorders Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE 1977 to June 2003), EMBASE (1977 to June 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised studies comparing BtA versus any anticholinergic drug for the treatment of cervical dystonia. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: We found only one trial suitable for inclusion and accordingly no meta-analysis was performed. It compared BtA versus trihexyphenidyl in 66 patients with cervical dystonia. Although this was a relatively small trial with short duration, the results can probably be generalized for the population, since the trial appears to be unbiased and produced clear clinically significant results. The results favoured BtA, and the difference was similar in size to that obtained in a systematic review comparing BtA with placebo. BtA was better tolerated. AUTHORS' CONCLUSIONS: The available evidence suggests that BtA injections provide more objective and subjective benefit than trihexyphenidyl to patients with cervical dystonia. We could not draw any conclusions about other anticholinergic drugs. Future trials should explore the role of anticholinergic drugs in patients that do not get benefit with BtA.

Botulinum Toxins, Type A↗
PubMed2005

Botulinum toxin type A versus botulinum toxin type B for cervical dystonia.

BACKGROUND: Cervical dystonia is the most common form of focal dystonia. It is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. Most cases are idiopathic, and generally it is a life-long disorder. In recent years, botulinum toxin type A (BtA) has become first line therapy for cervical dystonia. However, not all patients respond well to BtA, and 5 to 10% become resistant to it. Botulinum toxin B (BtB) is an alternative to BtA and offers the potential to help patients who do not respond to BtA. At present there is no compelling theoretical reason why it should not be as effective as, or even more effective than, BtA. OBJECTIVES: To compare the clinical efficacy and safety of BtA versus BtB in cervical dystonia. SEARCH STRATEGY: Studies for inclusion in the review were identified using the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, by handsearching the Movement Disorders Journal and abstracts of international congresses on movement disorders and botulinum toxin, by communication with other researchers in the field, by searching reference lists of papers found using the above search strategies, and by contact with authors and drug manufacturer. SELECTION CRITERIA: Studies were considered eligible for inclusion in the review if they evaluated the efficacy of BtA versus BtB for the treatment of cervical dystonia. Trials must have been randomised and placebo-controlled. DATA COLLECTION AND ANALYSIS: A paper pro-forma was used to collect data from the included studies using double extraction by two independent reviewers. Each trial was assessed for internal validity by each of the two reviewers. Differences were settled by discussion. The outcome measures used included improvement in symptomatic rating scales, subjective evaluation by patients and clinicians, changes in pain scores, changes in quality of life assessments, and frequency and severity of adverse events. MAIN RESULTS: We cannot give any results since we have only identified two ongoing trials and there are no preliminary results or interim analyses available for them. The full results of these trials are expected in late 2004 or 2005. AUTHORS' CONCLUSIONS: It is currently not possible to make definitive comparisons between BtA and BtB for the treatment of cervical dystonia; uncontrolled comparisons should be regarded with suspicion.

Botulinum Toxins↗
PubMed2005

Botulinum toxin type B for cervical dystonia.

BACKGROUND: Cervical dystonia is the most common form of focal dystonia. It is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. Most cases of cervical dystonia are idiopathic and generally it is a life-long disorder. In recent years, Botulinum toxin type A (BtA) has become the first line therapy. However, some patients become resistant to it. This problem led to the study of another Botulinum toxin (Bt) serotype, Bt type B (BtB) to address the issues of clinical efficacy, effect size, and safety of BtB in the treatment of cervical dystonia. OBJECTIVES: To determine whether botulinum toxin (BtB) is an effective and safe treatment for cervical dystonia. SEARCH STRATEGY: We identified studies for inclusion in the review using the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE; and by handsearching the Movement Disorders Journal and abstracts of international congresses on movement disorders and botulinum toxin, by communication with other researchers in the field, by searching reference lists of papers found using the above search strategies, and by contacting authors and drug manufacturers. SELECTION CRITERIA: We considered studies eligible for inclusion in the review if they evaluated the efficacy of BtB for the treatment of cervical dystonia in randomized, placebo-controlled trials. DATA COLLECTION AND ANALYSIS: We used a paper pro forma to collect data from the included studies with double extraction by two independent reviewers. Both reviewers assessed each trial for internal validity and settled differences by discussion. The outcome measures used included adverse events, improvement in symptomatic rating scales, subjective evaluation by patients and clinicians, changes in pain scores, changes in quality of life assessments. MAIN RESULTS: Studies were short term (16 weeks) employing a single BtB injection session. All were multicentre and conducted in the US. All patients included had previously received BtA. The trials differed with respect to whether or not the patients were still responding to BtA but other entry criteria were similar. All studies used a dose of 10,000 Units of BtB in one group and the technique of administration was the same. Meta-analysis of three trials enrolling 308 participants showed statistically and clinically significant improvements in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at week four with a Peto odds ratio (OR) for the number of patients who had at least a 20% improvement of 4.69 (95% CI 2.06 to 10.69) and a weighted mean difference of -5.92 (95% CI -9.61 to -2.23). Subjective rating scales (Patient Global Assessment of Change, Investigator Global Assessment of Change, and Patient Analog Pain Assessment) also improved. Adverse events clearly associated with the mechanism of action of BtB included dysphagia and dry mouth and the number of patients with any adverse event were more frequent in BtB treatment groups. Subgroup analyses showed a clear dose-response relationship for subjective and objective benefit, for frequency and severity of adverse events, and a greater benefit for BtA resistant patients than BtA responders in the primary outcome. The duration of effect was about 16 weeks. We found three eligible studies enrolling 308 participants. Studies were short term (16 weeks) employing a single BtB injection session. All were multicentre and conducted in the US. All patients included had previously received BtA. The trials differed with respect to whether or not the patients were still responding to BtA but other entry criteria were similar. Patient groups were appropriately selected and well matched. From the methodological point of view these trials were probably not subjected to important selection, performance or attrition bias and all studies used an intention-to-treat analysis.The dose varied significantly between studies although all used 10,000 Units of BtB in one group and the technique of administration was the same. The primary outcome in all trials was change in TWSTRS total score at week four and other efficacy outcomes were similar between studies. The number of dropouts was small and balanced in all trials. Reasons for withdrawals were given. One randomized double-blind placebo-controlled study was excluded because data couldn't be extracted for the outcomes. Meta-analysis showed statistically and clinically significant improvements with a Peto odds ratio (OR) of 20% in TWSTRS total score at week four (OR 4.69; 95% CI 2.06 to 10.69) and a weighted mean difference of -5.92 (95% CI -9.61 to -2.23). Subjective rating scales (Patient Global Assessment of Change, Investigator Global Assessment of Change, and Patient Analog Pain Assessment) also improved. The weighted mean difference for changes in these subjective scales varied between -13% to -21%. However, for many of the outcomes, we could not combine data from all studies. Only adverse events clearly associated with the mechanism of action of BtB were more frequent in the treatment group. These included dysphagia and dry mouth. The number of patients with any adverse event was more frequent with BtB. Subgroup analyses showed a clear dose-response relationship for subjective and objective benefit and for frequency and severity of adverse events. Subgroup analyses showed a greater benefit for the BtA resistant patients than BtA responders in the primary outcome. The duration of effect was about 16 weeks. These trials did not measure quality of life nor did they establish the long term duration of effect or immunogenicity AUTHORS' CONCLUSIONS: A single injection of BtB was effective and safe for treating cervical dystonia. Long-term uncontrolled studies suggested that further injection cycles continue to work for most patients. Future research should explore technical factors such as the optimum treatment intervals and use of image or electromyographic guidance for administration. Other issues include service delivery, quality of life, long-term efficacy and safety, and the relative indications for BtA, BtB and other treatments such as deep brain stimulation.

Botulinum Toxins↗
PubMed2005

Botulinum toxin type A therapy for hemifacial spasm.

BACKGROUND: Hemifacial spasm is characterised by unilateral involuntary contractions of muscles innervated by the facial nerve. The usual cause is a vessel touching the facial nerve near its origin from the brain stem. Although it is a benign condition it can cause significant cosmetic and functional disability. It is a chronic disease and spontaneous recovery is very rare. The two treatments routinely available are microvascular decompression and Botulinum Toxin type A (BtA) muscular injections. OBJECTIVES: To determine whether botulinum toxin (BtA) is an effective and safe treatment for hemifacial spasm. SEARCH STRATEGY: We searched the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1977 to December 2003), EMBASE (1977 to December 2003), and reference lists of articles. We also contacted drug manufacturers and researchers in the field. SELECTION CRITERIA: Randomised studies comparing BtA with placebo in people with hemifacial spasm. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: We found only one small randomised, placebo-controlled trial involving 11 people. It was a crossover trial during which patients underwent four sets of injections, comparing placebo with three different doses of BtA - formulation Botox(r) (low dose: one-half of the intermediate dose; intermediate dose; and high dose: twice the intermediate dose), and one of placebo. In this trial BtA was superior to placebo. AUTHORS' CONCLUSIONS: The findings of this single eligible trial support the results of large, open, case-control studies showing a benefit rate between 76 and 100%. This effect size probably makes it very difficult to perform new large placebo controlled trials for hemifacial spasm. Despite the paucity of good quality controlled data, all the studies available suggest that BtA is effective and safe for treating hemifacial spasm. Future trials should explore technical factors such as the optimum treatment intervals, different injection techniques, doses, Bt types and formulations. Other issues include service delivery, quality of life, long-term efficacy, safety, and immunogenicity. BtA should be compared with surgical microvascular decompression.

Botulinum Toxins, Type A↗
PubMed2005

Botulinum toxin type A therapy for blepharospasm.

BACKGROUND: Blepharospasm is a focal dystonia characterized by chronic intermittent or persistent involuntary eyelid closure due to spasmodic contractions of the orbicularis oculi muscles. Other facial and neck muscles are also frequently involved. Most cases are idiopathic and blepharospasm is generally a life-long disorder. Its severity can range from repeated frequent blinking to persistent forceful closure of the eyelids with functional blindness. Botulinum toxin type A (BtA) is the current first line therapy. OBJECTIVES: To determine whether botulinum toxin (BtA) is an effective and safe treatment for blepharospasm. SEARCH STRATEGY: We identified studies for inclusion in the review using the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, handsearches of the Movement Disorders Journal and abstracts of international congresses on movement disorders and botulinum toxin, communication with other researchers in the field, reference lists of papers found using above search strategies, and contact with authors and drug manufacturers. SELECTION CRITERIA: Studies were eligible for inclusion in the review if they evaluated the efficacy of BtA for the treatment of blepharospasm. They must have been randomised and placebo-controlled. DATA COLLECTION AND ANALYSIS: We used a paper pro-forma to collect data from the included studies using double extraction by two independent reviewers. The two reviewers separately assessed each trial for internal validity and they settled differences between them by discussion. The outcome measures used included adverse events, improvement in symptomatic rating scales, subjective evaluation by patients and clinicians, and changes in quality of life assessments. MAIN RESULTS: We found few controlled trials. They were of short duration and enrolled small numbers of patients. Because of their poor internal validity, the characteristics of the populations studied, and the types of interventions and outcomes, none of the trials fitted our criteria for inclusion. However, all these trials found BtA to be superior to placebo as did large case-control and cohort studies, which reported that around 90% of patients benefited. AUTHORS' CONCLUSIONS: There are no high quality, randomised, controlled efficacy data to support the use of Bt for blepharospasm. Despite this, other studies suggest that BtA is highly effective and safe for treating blepharospasm and support its use. The effect size (90% of patients benefit) seen in open studies makes it very difficult and probably unethical to perform new placebo-controlled trials of efficacy of BtA for blepharospasm. Future trials should explore technical factors such as the optimum treatment intervals, different injection techniques, doses, Bt types and formulations. Other issues include service delivery, quality of life, long-term efficacy, safety, and immunogenicity.

Blepharospasm↗
PubMed2005

Longitudinal analysis of heritability for dental caries traits.

The role of genetic and environmental factors on dental caries progression in young children was determined. A detailed caries assessment was performed in 2 examinations on 314 pairs of twins initially 1.5 to 8 years old. Surface-based caries prevalence rates (SBCPR) and lesion severity (LSI) were computed. Heritability estimates were calculated by SOLAR software. Analyses were performed on all ages combined and by age group (1.5-< 4; 4-6; > 6). Overall heritability estimates (H) of net increments SBCPRs were H = 30.0 (p < 0.0001), and were greatest for the youngest (H = 30.0) and oldest groups (H = 46.3). Overall LSI heritability estimates [H = 36.1 (p < 0.0001)] were also greatest for the youngest (H = 51.2) and oldest groups (H = 50.6). Similar findings were found for net increments of occlusal surfaces and deep dentinal lesions SBCPRs (H = 46.4-56.2). These findings are consistent with a significant genetic contribution to dental caries progression and severity in both emerging primary and permanent dentitions.

Age Factors↗
PubMed2004

Isolation and characterisation of a human anti-idiotypic scFv used as a surrogate tumour antigen to elicit an anti-HER-2/neu humoral response in mice.

HER-2/neu is a tumour antigen that is overexpressed in human breast tumours. Among the vaccine strategies developed to overcome immune tolerance to self-proteins, vaccination with anti-idiotypic (anti-Id) antibodies has been described as a promising approach for treatment of several malignant diseases. To develop an active immunotherapy for cancer patients positive for HER-2/neu, we investigated immunisation with human anti-Id single-chain fragments (scFv) mimicking the conformation of HER-2/neu protein to induce a humoral response in mice. We selected by phage display two human anti-Id scFv (Ab2beta) directed against trastuzumab F(ab')2 fragments (Ab1), a humanised anti-HER-2/neu monoclonal antibody. Using competitive ELISA and Biacore biosensor analysis, we showed that anti-Id scFv 40 and scFv 69 could inhibit HER-2/neu binding to trastuzumab. Following vaccination of BALB/c mice with the soluble or phage-displayed scFv, Ab3 polyclonal antibodies, and among them Ab1' antibodies able to bind HER-2/neu, were detected in the sera of the immunised mice. These results demonstrate that the human anti-Id scFv could act as a surrogate antigen for HER-2/neu. The present study strongly suggests that the novel 30 kDa human mini-antibody could be used as an anti-idiotype-based vaccine formulation to induce an effective humoral response in patients bearing HER-2/neu-positive tumours.

Animals↗
PubMed2004

[Concomitant use of radiotherapy and gemcitabine: preclinical findings and clinical practice].

Gemcitabine is pyrimidine analog which has demonstrated antitumoral activity in a variety of solid tumors. Laboratory studies demonstrating that gemcitabine is a potent radiosensitizer led to a variety of trials combining radiation and gemcitabine. In the clinic, phase I-II studies are still trying to determine the optimal dose and schedule which could be use in daily clinical practice. This review summarizes the mechanisms of interaction between radiotherapy and gemcitabine and presents several therapeutic schemes for each tumor location.

Adenocarcinoma↗
PubMed1997

Seizure symptomatology in infants with localization-related epilepsy.

The clinical characteristics of seizures in adults and children with localization-related epilepsy have been clearly described and classified, but few data are available based on video EEG studies of postneonatal infants under 2 years of age. We analyzed 125 videotaped seizures from 23 infants aged 2 to 24 months with localization-related epilepsy defined by localized ictal EEG or localized lesion on neuroimaging with seizure-free surgical outcome. Seizure symptomatology was classified based on observable behavioral and motor manifestations and then correlated with location of the epileptogenic zone. Seizures characterized by decrease in behavioral motor activity with indeterminate level of consciousness and minimal or no automatisms ("hypomotor" seizures) arose from temporal, temporoparietal, or parieto-occipital regions (7 patients). Seizures with localized or bilateral clonic, tonic, or atonic motor phenomena arose predominantly from frontal, frontocentral, central, or frontoparietal areas (12 patients). One patient had versive seizures arising from the contralateral occipital lobe, 2 patients had infantile spasms (one with a frontal tumor, one with temporo-parieto-occipital dysplasia), and one patient had unclassifiable seizures. Disruption of temporal or temporoparietal function resulted primarily in diminution of behavioral activity, whereas ictal activation of motor areas during frontal or central onset seizures resulted mainly in localized or generalized motor phenomena. Infantile spasms occurred because of lesions in either location. Using an approach based on easily observable behavioral and motor phenomena, it was possible to classify the seizures in all but one infant.

Brain↗
PubMed1996

Usefulness of prolonged video-EEG monitoring in the elderly.

The diagnosis of epilepsy in the elderly can be difficult. We sought to determine whether video-EEG monitoring (VEEG) is useful in the diagnosis and management of elderly patients with epilepsy. We reviewed the medical records of 20 consecutive patients, over 60 years of age, selected from a total of 1423 patients referred over a five year period for VEEG evaluation for epilepsy. The usefulness of VEEG was assessed by comparing changes in (a) the diagnosis and treatment of these patients before and after VEEG, and (b) the assessments made by an epileptologist who reviewed medical records before and after receiving results of VEEG. Compared to the initial diagnosis by the referring physician, VEEG resulted in changes in either the diagnosis or treatment in 11/20 patients based on the results of VEEG. The epileptologist was able to correctly assess the diagnosis and treatment of 16/20 patients without knowledge of the VEEG results. In 4/20 cases, the VEEG provided additional information to the epileptologist. In selected elderly patients, VEEG is useful in establishing the diagnosis of epilepsy, and may change the management of these patients.

Aged↗
PubMed1995

Survival predictors in advanced non-small cell lung cancer.

The authors studied the influence on survival of 21 clinical, anatomical, haematological and biochemical factors evaluated, at diagnosis, of 411 patients (pts) with advanced Non Small Cell Lung Cancer (NSCLC) followed in our department between 1984 and 1990. Most of the patients were male (347--84.4%) and only 64 (15.6%) were females. Median age was 62 years, but was slightly higher in females. Only 34 patients were aged under 45 years. Squamous cell carcinoma (215 pts--52%) and adenocarcinoma (152 pts--37%) were the most frequent histologic types. Performance status was poor--only 103 (25%) continued active; 120 (29%) spent at least half of the time in bed; 188 (46%) were severely limited. After staging, 179 (44%) presented locally advanced disease (stage IIIB) and 232 (56%) metastatic dissemination (stage IV). Therapy was defined by the oncologic group according to individual characteristics and based on clinical grounds. Anti-neoplastic therapy was performed in 225 (55%), chemotherapy alone in 121 (30%), radiation therapy alone in 67 (16%), and sequential combined treatment (chemotherapy and thoracic radiation) in 37 (9%). Until 1987, the main chemotherapy regimen was MACC (Metrotrexate + Adriamycine + Cyclophosphamide + Lomustin), afterwards VP(M) (Cisplatin + Vimblastin + Mitomycine). Radiation therapy was performed using Co60, 2 Gy/day, 5 days a week, for 4 weeks (approximately 45 Gy total). The response rate was poor--four complete responses (2%), 42 (19%) partial responses. The overall median survival was 4.3 months and only 5% of patients were alive after 18 months of follow up. Prognostic importance of each characteristic studied was initially done by unifactorial analysis, followed by multifactorial analysis according to two methods: Cox proportional hazards model and recursive partitioning amalgamation--RECPAM. Regardless of the method used, the main determinants of survival were found to be performance status (Zubrod), weight loss and serum albumin. Other factors such as the staging (presence or absence of metastasis), lymphocytes, lactic dehydrogenase, and hoarseness were also significant. It is noteworthy that age and histological type were irrelevant; sex and hoarseness only proved important when integrated within a multifactorial model. The overall prognostic evaluation and therapeutic decision of advanced NSCLC patients could be improved by combining the prognostic value of TNM with that of performance status, weight loss and serum albumin. These prognostic guidelines must be taken into account when designing new clinical trials.

Adenocarcinoma↗
PubMed1995

[The course of care for cancer patients hospitalized in a central hospital].

Prevention and early diagnosis are considered the main tools to reduce the incidence and mortality from cancer. The authors studied prospectively 150 oncologic patients admitted to Santa Maria Hospital-Lisbon from April/92 to April/93, by personal interview, to analyze their assistance pathways from the appearance of first symptoms. We tried to define the role of the different medical assistance structures and the most important factors conditioning delay in diagnosis and therapeutics. The results show that primary care physicians were the first medical assistance in 56% of patients; 22% of the patients went to the Emergency Service of the Hospital for the first time. Duration of symptoms was less then 3 months in 74% of the population studied. Primary care physicians diagnosed neoplasia in 32% of the cases and prescribed symptomatic treatment in another 41%. The Emergency Service was the most efficient in diagnosis, providing rapid orientation in 91% of patients. In this population, 43% had their residence more than 30 km from Lisbon. Median age was less than 60 years. These results emphasize the fundamental role of Primary Care Physicians in the initial management of cancer patients and their responsibility in early diagnosis. They also suggest the need for the promotion of graduate education and courses designed for primary care physicians and the population.

Aged↗
PubMed1990

Usefulness of immunocytochemical demonstration of neuron-specific enolase in the diagnosis of Hirschsprung's disease.

The work reported here was carried out to study the importance of immunocytochemical staining of neuron-specific enolase (NSE) in the diagnosis of Hirschsprung's disease and to compare its results with those obtained by hematoxylin-eosin (H&E) staining in consecutive sections. A retrospective study was made on 51 rectal mucosal biopsies and 19 colorectal surgical specimens from 52 patients clinically suspected of Hirschsprung's disease. Several consecutive sections from all cases were restained by H&E and for NSE demonstration. Sixteen (31%) patients had a histological diagnosis of Hirschsprung's disease, 9 (17%) had hypoganglionosis, 4 (8%) had neuronal intestinal dysplasia, and 2 (4%) had normal histology. In eight patients (15%) hypoganglionosis remained dubious, and in 10 (19%) the diagnosis was inconclusive. Although the NSE staining improved the identification of the nervous tissue of the colon, both H&E and NSE staining proved to be of equal value in the assessment of the presence of neurons in the rectal wall of people with clinically suspected cases of Hirschsprung's disease. Ten H&E-stained sections from different levels of the biopsy specimen would be enough to detect ganglion cells in most cases.

Adolescent↗
PubMed1989

Effect on EEG responses of removing ocular artefacts by proportional EOG subtraction.

Work undertaken to investigate the effect on EEG responses of ocular artefact removal by proportional electro-oculogram subtraction using the least-squares method is reported. The ocular artefact model and the least-squares approach to estimation of the model parameters and hence of the EEG waveform, including the response, are described. Results are presented to show that the response shapes become modified if ocular artefact removal is implemented recursively. This happens because the response is incorrectly treated as part of the random background EEG. The solution is to incorporate a model of the response within the ocular artefact removal algorithm. The results of tests on simulated data confirm these conclusions. The results of the incorporation of response models in removing ocular artefacts from CNV recordings are presented. Even with modelling recursive ocular artefact removal is found to modify the shape of the CNV, and so reliable results can only be obtained if the removal is implemented nonrecursively. Evidence is given that it is advisable to remove DC levels from the recorded data.

Electroencephalography↗
PubMed1989

Spectral analysis of EEG responses.

The techniques used and the results obtained in a spectral analysis of two specific responses in the human electroencephalogram are presented in this paper. The purposes are to show how the techniques may be applied to the necessarily short lengths of EEG data and to illustrate these techniques and the useful results obtained by relevant examples. The necessary data-processing procedures and precautions for transforming from the time to frequency domain are presented in a tutorial fashion. The importance of augmenting zeros, choice of the most appropriate data window and pretransformation of the data to avoid the combined effects of energy loss and low frequency content biasing caused by windowing is explained. The pros and cons of the tapered-cosine (Tukey) and Kaiser-Bessel windows are illustrated. The usefulness of applying certain statistical tests, which are based on a physical model of the responses, to the harmonic components of the responses is demonstrated. Thus a comparison is made between the features of auditory evoked responses and of the contingent negative variation, and the usefulness of predictive statistical diagnosis in differentiating between subject groups is illustrated by application to normal subjects and Huntington's chorea patients.

Biomedical Engineering↗
PubMedDate not supplied

Can a low or moderate dose of inhaled budesonide replace oral non-steroidal anti-asthma treatment?

The efficacy of inhaled budesonide was assessed as an adjunct to and as a replacement for oral bronchodilators in an open study of 27 asthmatic patients. The patients had been treated regularly with oral bronchodilators but not with oral inhaled, or nasal steroids during the 2 3 months prior to the study. The study consisted of four treatment periods: 1, oral bronchodilator plus inhaled placebo for 1 week; 2, oral bronchodilator plus 400 micrograms inhaled budesonide twice daily for 3 weeks; 3,400 micrograms inhaled budesonide twice daily for 3 weeks; 4,200 micrograms inhaled budesonide twice daily for 3 weeks. Lung function measurements increased when budesonide was included with oral bronchodilators and there was a corresponding decrease in symptoms and rescue inhaler usage. Removal of oral bronchodilators from therapy did not significantly alter lung function and symptoms, whereas decreasing the dose of budesonide produced a slight reduction in peak expiratory flow and an increase in inhaled bronchodilator consumption.

Administration, Inhalation↗