Nine novel mutations in the hydroxymethylbilane synthase gene of Polish patients with acute intermittent porphyria.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
A Gregor
Publications and source records attributed to A Gregor.
Symptom control and quality of life in people with lung cancer: a randomised trial of two palliative radiotherapy fractionation schedules.
AIMS: To determine whether palliation of chest symptoms from a 10 Gy single fraction (regimen 1) was equivalent to that from 30 Gy in 10 fractions (regimen 2). MATERIALS AND METHODS: Patients with cytologically proven, symptomatic lung cancer not amenable to curative therapy, with performance status 0-3, were randomised to receive either 30 Gy in 10 fractions or a 10 Gy single fraction. Local symptoms were scored on a physician-assessed, five-point categorical scale and summed to produce a total symptom score (TSS). This, performance status, Hospital Anxiety and Depression (HAD) score and Spitzer's quality-of-life index were noted before treatment, at 1 month after treatment and every 2 months thereafter. Palliation was defined as an improvement of one point or more in the categorical scale. Equivalence was defined as less than 20% difference in the number achieving an improvement in the TSS. RESULTS: We randomised 149 patients and analysed 74 in each arm. According to the design criteria, palliation was equivalent between the two arms. TSS improved in 49 patients (77%) on regimen 1, and in 57 (92%) patients on regimen 2, a difference of 15% (95% confidence interval [CI] 3-28) in the proportion improving between the two regimens. A complete resolution of all symptoms was achieved in three (5%) on regimen 1, and in 14 (23%) patients on regimen 2 (P < 0.001), a difference in the proportion between the two regimens of 21% (95% CI 10-33). A significantly higher proportion of patients experienced palliation and complete resolution of chest pain and dyspnoea with regimen 2. No differences were observed in toxicity. The median survival was 22.7 weeks for regimen 1 and 28.3 weeks for regimen 2 (P = 0.197). CONCLUSIONS: Although this trial met the pre-determined criteria for equivalence between the two palliative regimens, significantly more patients achieved complete resolution of symptoms and palliation of chest pain and dyspnoea with the fractionated regimen.
Aged↗
Early age of onset in fatal familial insomnia. Two novel cases and review of the literature.
Fatal familial insomnia (FFI) is a prion disease exhibiting the PRNP D178N/129M genotype. Features of this autosomal dominant illness are progressive insomnia, dysautonomia, myoclonus, cognitive decline and motor signs associated with thalamic nerve cell loss and gliosis. In contrast to the new variant of Creutzfeldt-Jakob disease (vCJD) the onset of FFI is in middle to late adulthood. We report two male patients who belong to a large German FFI kindred. They were examined clinically, and postmortem neuropathological examination was carried out in collaboration with the German reference centre for prion disease. Additionally, the prion protein gene (PRNP) was analysed. To identify further patients with disease onset under 30 years of age a comprehensive literature review was carried out. Two male patients presented with typical symptoms of FFI at the age of 23 and 24 years. In their kindred, the age of onset has never before been under 44 years of age. Our literature review identified five additional early onset cases who died at age 21 to 25 years. In all 22 reviewed FFI families the median manifestation age was 49.5 years. Although phenotypic variability of FFI is common, age of onset under 30 years has been considered to be a hallmark of vCJD with a mean manifestation at 27 years of age. Our findings underline that in addition to vCJD, FFI must be considered in cases of young-onset prion disease. This has considerable impact on clinical management and genetic counselling.
Adult↗
Mutation hotspots in the human porphobilinogen deaminase gene: recurrent mutations G111R and R173Q occurring at CpG motifs.
Acute intermittent porphyria (AIP) is an inherited disorder in the haem biosynthetic pathway caused by a partial deficiency of porphobilinogen (PBG) deaminase. To date, more than 200 different mutations have been identified in the PBG deaminase gene (PBGD) in AIP patients from various countries and ethnic groups. While the majority of the PBGD gene mutations, including most of the mutations occurring at CpG dinucleotides, are family-specific, a few CpG mutations have been observed in a number of AIP patients of European origin. To study the origin of these common CpG mutations, eight intragenic single-nucleotide polymorphisms (SNPs) in the PBGD gene, as well as eight microsatellites flanking the gene in chromosome 11 were used to construct haplotypes in six AIP families of German, Polish and Swiss origins who carried either G111R (4707G>A) or R173Q (6391G>A) mutations. Among the three R173Q families, three distinct haplotypes were found to be cosegregated with the mutation. One Swiss and one German G111R family shared partially an intragenic and its extended microsatellite haplotype, whereas the Polish G111R family showed a unique haplotype. These results indicated that the recurrent CpG mutations that exist in the European AIP population can be either of ancestral origins or derived from de novo events.
Chromosome Mapping↗
Induction treatment before surgery for non-small cell lung cancer.
Surgery alone is currently still accepted "standard of care" for patients with operable NSCLC, this includes stages IA and IIB, as well as selected early subsets of IIIA disease. In more advanced and inoperable stage III disease, combinations of chemotherapy and radiotherapy remain the standard treatment approach for patients with good performance status. The role of surgery following induction therapy in these advanced stage III patients is at the moment not conclusively defined. More evidence from randomized trials is clearly needed to tailor treatment for the large number of patients that present in these locally advanced stages. Enrollment of patients into ongoing prospective clinical trials should be encouraged, whenever possible, to further define prognostic factors and improve multimodality strategies in this clinical setting.
Antineoplastic Combined Chemotherapy Protocols↗
Managed clinical network in practice--is it working?
Explore the source record for details and available documents.
Cancer Care Facilities↗
Practical problems with the collection and interpretation of serial quality of life assessments in patients with malignant glioma.
OBJECTIVES: To assess the problems involved with the collection and interpretation of serial collected health related quality of life assessments in patients with malignant glioma. PATIENTS AND METHODS: One-hundred and fifty nine patients with malignant glioma from three Scottish neurosurgical centres in whom assessments of performance status, neurological impairment, mood, and quality of life had been recorded over a 6-month period were prospectively identified. The amount of missing data and the reasons for missing data were assessed. Characteristics of patients that were fully compliant with serial assessments were then compared with those that were not. RESULTS: Compliance with serial assessments (both patient and observer reported) was poor, dropping to less than 50% at 6 months. Observer reported measures showed a similar pattern of decline as patient reported measures. The largest single cause of missing data (approximately 70%) was due to administrative failure. Compliant patients were found to have a significantly greater probability of survival compared to non-compliant patients and were also found to be younger and fitter relative to the rest of the study population. CONCLUSIONS: Studies utilising quality of life outcomes should give early consideration to minimising avoidable sources of missing data and recording the reasons for non-compliance. Quality of life studies basing conclusions on a complete case analysis should be wary of possible bias.
Bias↗
The prognostic influence of bcl-2 in malignant glioma.
The bcl-2 gene is one of a complex group of genes which control programmed cell death. Bcl-2 acts to extend cell survival by blocking apoptosis, and thereby may influence tumour prognosis. This study of 187 high grade gliomas reviews clinicopathological prognostic features and the relationship to bcl-2 expression. Bcl-2 immunostaining was assessed in 159 specimens from these patients, by scoring systems of 0 to 3 for intensity of scoring and proportion of cells staining. Age, histology, pre- and post-operative performance status were found to be strongly predictive of survival (log rank test P<0.0001). The type of surgery performed did not influence survival in this group of patients. The expression of bcl-2 had a significant relationship with survival (univariate Cox model P=0.0302, hazard ratio 0.8, 95% confidence interval 0.65-0.98), with increased staining associated with improved survival. Multivariate analysis showed performance status, histology and proportion of cells staining for bcl-2 to be independently predictive of survival. Bcl-2 staining was not related to histological grade of tumours.
Adolescent↗
The treatment of a thyrotropin-secreting pituitary macroadenoma with octreotide in twin pregnancy.
TSH-secreting pituitary tumours are rare but difficult to treat due to a combination of refractory hyperthyroidism and low surgical cure rates. We describe the case of a 21-year-old woman who, despite twin pregnancy, became euthyroid and had dramatic tumour shrinkage on octreotide treatment. To our knowledge, this is the first description of the use of octreotide for a TSH-secreting pituitary adenoma throughout pregnancy.
Adenoma↗
Antitumour and pro-apoptotic actions of highly unsaturated fatty acids in glioma.
The highly unsaturated fatty acids (HUFA) of the n-6 and n-3 series are involved in cell signalling in normal and transformed cells and have recently been associated with pathways leading to tumour cell death. The antitumour activity of three HUFA (arachidonic acid, gamma linolenic acid and eicosapentaenoic acid) were studied in glioma cells and tissue. Using five glioma models, including primary cell suspensions prepared from 46 human glioma samples and an in vivo rat C6 glioma model, we obtained evidence that, following exposure to HUFA, either administered into the medium surrounding human glioma cells or in 16 preparations of multicellular spheroids derived from human and rodent glioma cell lines (C6, MOG, U87, U373) or administered intra-tumourally by infusion using osmotic mini-pumps in 48 rats, glioma regression and apoptosis were detected. Additionally, synergy between gamma irradiation and HUFA administration was observed in 13 experiments analyzing C6 glioma cell apoptosis in vitro. These pro-apoptotic and antiproliferative activities were observed using both C18 and C20 fatty acids of the n-6 and n-3 series, but not when saturated and monounsaturated C18 and C20 fatty acid preparations were used. In the glioma infusion model, in addition to the apoptosis detected in glioma tissue infused with HUFA for 3-7 days, preservation of normal neural tissue and vasculature in adjacent brain was observed. Also, there was little evidence of acute inflammatory infiltration in regressing tumours. Our findings suggest that intraparenchymal infusion of HUFA may be effective in stimulating glioma regression.
Animals↗
Management of patients aged >60 years with malignant glioma: good clinical status and radiotherapy determine outcome.
Many clinical trials have shown that the most important prognostic variable in patients with malignant glioma is advanced age. However, can some patients aged >60 years still have relatively good outcomes with conventional surgical and radiotherapeutic treatment? A previous audit of practice (1983-89) suggested that functional status was an important prognostic variable in the elderly. We have reviewed a further cohort (1989-96) to evaluate changes in practice and outcomes given advances in neuroimaging, neurosurgery and radiotherapy. The major findings in this series of 80 patients aged over 60 years with a histological diagnosis of supratentorial malignant glioma were: (i) There was a relationship between management undertaken and clinical status of the patients (p < 0.01), i.e. patients in good grade generally had tumour debulking and radiotherapy, whilst those in poor grade generally had only biopsy. (ii) There was a significant increase in survival of patients in the second period who received surgical debulking and post-operative radiotherapy (from a median of 23 to 41 weeks (p < 0.05). (iii) It is likely that case selection accounted for much of this improvement since there was a direct relationship between median survival time and good clinical grade using the WHO performance scale. (iv) A shorter radiotherapy course (30 Gy in six fractions) was as efficacious as a conventional course (60 Gy in 30 fractions), and those patients having radiotherapy survived significantly longer than those not having this treatment (p = 0.001). This study has again demonstrated the importance of preoperative clinical grade and radiotherapy treatment in determining outcomes in patients >60 years. To put these data in a societal context a recent prospective multicentre audit of patients with malignant glioma in Scotland, and another audit from our unit, showed that between 24 and 65% of patients aged >60 years, with a CT diagnosis of malignant glioma do not undergo either surgery or radiotherapy. Advanced age per se should not be a bar to interventional treatment in patients aged >60 years with suspected malignant glioma.
Age Factors↗
[Quality of life of severely injured patients 1 year after trauma. A matched-pair study compared with a healthy control group].
PURPOSE: Severe trauma is accompanied not only with functional disabilities, but also with pain, social and psychological problems of the patient. Those four aspects are important components of the construct quality of life (QoL). The purpose of this study was to evaluate different questionnaires and to compare results between multiply injured patients and healthy controls. METHODS: A group of 43 severely injured patients was matched according to age, gender, educational status and family life situation to 43 persons who had never experienced a severe injury. For the assessment of all four aspects of QoL the patients completed validated questionnaires: Beck-Depression-Inventory (BDI), Short Form Health Survey (SF-36), State-Trait Anxiety Inventory (STAI), a questionnaire for locus of control (KKG), and a questionnaire for social support (SOZU). RESULTS: Patients and the control group showed remarkable differences: 22 of 43 trauma patients suffered from bad health perception (subscale of SF-36) (8/43 control persons), 21 trauma patients reported moderate to severe pain (5/43 control persons), 11 of 43 trauma patients suffered from anxiety (4/43 control persons) and 10 of 43 trauma patients complained about depressive symptoms (2/43 control persons). CONCLUSION: One year after trauma, patients suffer from severe impairments, some even in all four aspects of QoL. The questionnaires used are very well applicable to patients after severe injuries. A trauma-specific Quality of Life Instrument is lacking--and is currently developed by the german trauma registry group.
Adaptation, Psychological↗
Long-term survival in patients with non-small cell lung cancer treated with palliative radiotherapy.
The aim of palliative thoracic radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) is to alleviate symptoms. This study was designed to determine whether any patients achieved long-term survival after this treatment. In Edinburgh, between 1974 and 1993, 4531 patients were treated with palliative radiotherapy for NSCLC, receiving ten fractions or fewer. We reviewed the case notes of the long-term survivors. Sixty-one (1.3%; 95% confidence interval (CI) 1.0-1.6) patients survived for more than 5 years; 43 (70%) had histological confirmation of cancer; 28 (46%) had stage Stage I or II, 28 (46%) Stage III and one Stage IV disease; 53 (87%) patients were treated with doses of 30-35 Gy in ten daily fractions, seven (12%) received 20 Gy in five daily fractions and one received a 10 Gy single fraction. Forty-two (69%) patients had a radiological complete response, 16 (26%) a partial response and the remainder stable disease. Clinically significant radiation pneumonitis occurred in one (2%) patient, radiation myelopathy in two (3%) and multiple rib fractures in one (2%). There did not appear to be an association between long-term survival and a radiosensitive phenotype. On univariate analysis, long-term survival was more frequent in patients receiving ten-fraction regimens than in those who underwent a shorter course of radiotherapy (chi 2 = 19.5, P < 0.001). Thirty-four (0.8%; 95% CI 0.6-1.0) patients were disease free at death or at last review (median 10 years; range 5-17). We conclude that palliative thoracic radiotherapy produces long-term survival in 1.3% and personal cure in up to 1% of patients with advanced NSCLC.
Aged↗
Management and survival of patients with lung cancer in Scotland diagnosed in 1995: results of a national population based study.
BACKGROUND: The prognosis of patients with lung cancer in Scotland is poor and not improving. This study was designed to document factors influencing referral, diagnostic evaluation, treatment, and survival in patients with lung cancer. METHODS: Patients diagnosed during 1995 were identified from the Scottish Cancer Registry and their medical records were reviewed. Adequate records were available in 91.2% of all potentially eligible cases. RESULTS: In 1995, patients in Scotland with lung cancer had a high rate of microscopic verification (74.1%) and 75.3% were assessed by a respiratory physician; however, only 56.8% received active treatment (resection 10.7%, radiotherapy 35.8%, chemotherapy 16.1%) and 2.9% participated in a clinical trial. Survival was poor with a median of 3.6 months; 21.1% (95% CI 19.8% to 22.4%) were alive at 1 year and 7.0% (95% CI 6.2% to 7.8%) at 3 years. Management by respiratory physician, oncologist, or thoracic surgeon was an independent predictor of access to potentially curative treatment and better survival. CONCLUSION: This national population based study demonstrates low use of treatment, poor survival, and the influence of process of care on survival. Implementation of evidence-based guidelines will require substantial changes in practice. Increasing the number of patients who receive treatment may improve survival.
Adult↗
New missense mutation in the human ferrochelatase gene in a family with erythropoietic protoporphyria: functional studies and correlation of genotype and phenotype.
Explore the source record for details and available documents.
Adolescent↗
[Uniform programme in caring for patients with acute hepatic porphyria].
The programme commissioned by the Ministry of Health is presented. Data basis for the years 1996-1998 were created. A booklet on diagnosis, treatment and prophylaxis of porphyrias was edited and distributed in Poland in 5000 copies to all hospitals, major laboratories, medical libraries, regional officers as well as patients. The booklet lists simple diagnostic methods which can be easily introduced to hospital laboratories for early diagnosis of porphyria. It also includes a list of the safe drugs for patients with porphyria. Several lectures for doctors and medical staff were delivered, nine publications appeared and six others were accepted for publication. Results of the work, evaluated after three years are as follows. Early clinical diagnosis of porphyria and its prophylaxis among family members has significantly improved. The frequency of severe attacks and the mortality rate due to porphyria has been reduced to singular cases. The proposed organization of small regional centers (with help of Porphyria Center), oriented at early diagnosis of porphyria appears to be impossible without further financial support.
Guidelines as Topic↗
Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group.
PURPOSE: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation. PATIENTS AND METHODS: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain. RESULTS: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087). CONCLUSION: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.
Adult↗
A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy.
BACKGROUND: The role of chemotherapy in the treatment of patients with primary central nervous system lymphoma (PCL) remains unclear, with no randomized trials available to aid in the interpretation of the current data. The Medical Research Council therefore conducted the current randomized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in nonimmunocompromised adult patients with pathologically proven PCL. METHODS: After surgery, patients were randomized at a ratio of 1:2 to radiotherapy alone (RT: 40 grays [Gy] in 20 fractions to the whole brain followed by a 14-Gy boost to the tumor plus a 2-cm tumor margin) or to the same radiotherapy followed by six cycles of CHOP chemotherapy given at 3-week intervals (RT-CHOP). The target sample size was 90 patients, which allowed 90% power to detect a doubling of the median survival time. RESULTS: Between 1988 and 1995, 53 patients were randomized: Fifteen patients were randomized to RT, and 38 patients were randomized to RT-CHOP. The trial closed earlier than planned through poor accrual. The median patient age was 57 years, 57% of the patients were male, and 75% of the patients had unifocal disease. The median number of chemotherapy cycles received was 6 (mean, 4 cycles). Forty-three patients have died, and the median follow-up of survivors is 5 years (range, 1-9 years). There was no evidence of a benefit from RT-CHOP with respect to overall survival (hazard ratio [HR], 1.19; 95% confidence interval, 0.51-2.76) after adjustment for prognostic factors (patient age and neurologic performance status) in an analysis in which HR > 1 favored the control (RT) group. CONCLUSIONS: CHOP has no clear role in the postradiotherapy treatment of patients with PCL. Chemotherapy is poorly tolerated and largely palliative in older, less fit patients. In younger patients, initial chemotherapy designed to penetrate the blood-brain barrier warrants further investigation.
Adult↗