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PubMed2003

A polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women.

BACKGROUND: The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance. OBJECTIVE: To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women. DESIGN: Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated. RESULTS: A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity. CONCLUSION: The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.

Adult↗
PubMed1997

Primary hepatic non-Hodgkin's lymphoma in children: a case report and review of the literature.

Non-Hodgkin's lymphomas presenting exclusively in the liver are rather uncommon in adults and extremely rare in children. We describe a six-year-old white boy with jaundice, abdominal pain, and weight loss of two weeks duration. Physical examination disclosed asthenia, jaundice, abdominal swelling, large hepatomegaly, and ascitis. Aminotransferases bilirubin, and alkaline phosphatase were significantly elevated. Bone marrow aspiration, cerebrospinal fluid, chest x-ray, renal function tests, and uric acid were normal. Abdominal ultrasound showed liver enlargement with irregular regular borders, many parenchymal nodules in both liver lobes, a large hypoechogenic mass in the inferior segment of the liver, normal biliary ducts and two pancreatic nodules resembling those in the liver. Liver needle biopsy disclosed diffuse lymphomatous infiltration. Blast cells were positive for leukocyte common antigen (CD 45). Immunohistochemistry study for T or B cell lineage differentiation was not done. The child showed an excellent response to chemotherapy based on the BFM-83 protocol for B cell non-Hodgkin's lymphomas. The patient had his therapy discontinued in June 1995 and remains in first complete remission as of May 20th, 1996.

Child↗
PubMed1996

Consolidation biochemotherapy for patients with advanced nonsmall cell lung carcinoma responding to induction PVM (cisplatin, vinblastine, mitomycin-C) regimen. A phase II study.

BACKGROUND: The authors investigated a consolidation biochemotherapy program with subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN alpha) biologic response modifiers (BRM) in patients with advanced nonsmall cell lung carcinoma (NSCLC) with responsive or stable disease to induction chemotherapy. METHODS: Patients with proven, advanced, previously untreated NSCLC were entered into the study. Induction chemotherapy consisted of cisplatin, 120 mg/m2 intravenously (i.v.), on Day 1; vinblastine, 6 mg/m2 i.v., on Day 1; and mitomycin-C, 6 mg/m2 i.v., on Day 1 (PVM), every 3 weeks. Subsequently, patients with complete response (CR), partial response (PR), and stable disease (SD) received consolidation biochemotherapy with subcutaneous rIL-2, 3 MU/m2 twice/day, and rIFN alpha, 3 MU once/day, 5 days a week, starting 2 weeks after the second PVM course. After 3 and 6 weeks of BRM treatment, patients had a 14-day rest period to intercalate consolidating PVM courses. RESULTS: Seventy-seven patients were enrolled in the trial. After 2 PVM induction courses, 16 patients progressed and went off the study, whereas 61 patients were eligible for consolidation biochemotherapy. Among the 61 patients, 9 were not treated with BRM for several reasons, whereas 52 patients began biochemotherapy and were evaluable for toxicity. Furthermore, a few days after starting BRM, 9 patients discontinued therapy due to side effects; the remaining 43 patients received adequate treatment and were fully evaluable. In the 52 evaluable patients, the following BRM related toxicities were observed: World Health Organization (WHO) grade 2-3 fever in 85% of patients, asthenia in 71%, anorexia in 63%, and flu-like syndrome in 18.5%. PVM-related vomiting was present in 19% of patients. WHO Grade 3-4 myelosuppression, from both BRM and PVM (overlapping toxicity), was anemia in 16% of patients, leukopenia in 12%, and thrombocytopenia in 19%. There were three toxic deaths: two due to BRM-induced hypotension and one from pneumonia. In the 43 fully evaluable patients (23 PR and 20 SD after induction chemotherapy), after a median of 6 weeks of biochemotherapy (range, 3-16 weeks), we observed 5 of 20 patients achieving PR from SD, and 6 of 23 with confirmed PR. In these 11 patients, the median duration of response was 21 weeks (range, 7-80 weeks). Overall response improvement was 11.6% in the 43 patients and 6.4% in the 77 total enrolled patients. Median survival was 41 weeks (range, 15-173 weeks) in the 43 patients and 38 weeks (range, 1.4-173 weeks) in the 77 patients. CONCLUSIONS: In this study, biochemotherapy, when administered by this dose and schedule, did not offer substantial benefit although it caused significant toxicity.

Adult↗
PubMed1996

Cisplatin, epirubicin, and vindesine with or without lonidamine in the treatment of inoperable nonsmall cell lung carcinoma: a multicenter randomized clinical trial.

BACKGROUND: Lonidamine (LND) is an indazol-carboxylic acid derivative that selectively inhibits the energy metabolism of neoplastic cells, and increases the permeability of cell membranes. In vitro studies have demonstrated that LND can potentiate the oncolytic activity of cytotoxic drugs and is able to reverse the acquired multidrug resistance of neoplastic cells. Some clinical trials have suggested a synergism of LND with alkylating agents, cisplatin, and anthracyclines in various solid tumors. METHODS: From June 1990 to June 1993, 158 previously untreated patients with Stage IIIB and IV nonsmall cell lung cancer (NSCLC) were enrolled into a multicentric randomized trial to evaluate the addition of LND to a cisplatin-epirubicin-vindesine regimen. Eighty patients in the control arm (A) received cisplatin, 60 mg/m2 intravenously (i.v.); epirubicin, 60 mg/m2 i.v.; and vindesine, 3 mg/m2 i.v. (PEV), on Day 1 every 4 weeks, whereas 78 patients in the experimental arm (B) received the same regimen with the addition of LND from 75 mg orally three times on Day 1 to 150 mg orally three times on Day 7+ until tumor progression occurred. RESULTS: The experimental treatment achieved a significantly higher proportion of major responses in comparison with the control regimen (43% vs. 24%; P=0.02). The addition of LND apparently potentiated the activity of this cytotoxic treatment, particularly in patients with metastatic disease (overall response rate, 39% vs. 17%). The median time to progression (5 vs. 8 months; P=0.0007) and the median survival time (7.6 vs. 11 months; P=0.0013) were also statistically improved in Arm B. The acute toxicity of the 2 treatments was low: only 6% of patients in Arm A and 4% of patients in Arm B had to withdraw from treatment due to Grade 4 World Health Organization toxicity. The main additional side effects related to the administration of LND were epigastralgia, myalgia, asthenia, and orchialgia. However, these symptoms were mild and controlled by the concomitant administration of low doses of steroids. CONCLUSIONS: The mild acute toxicity of the PEV regimen and the acceptable and nonoverlapping additional side effects of LND render our experimental therapy worthy of consideration for the management of NSCLC patients with poor performance status or low tolerance to more aggressive therapeutic approaches.

Aged↗
PubMed1999

The role of cytokines in cancer cachexia.

A large number of observations point towards cytokines, polypeptides released mainly by immune cells, as the molecules responsible for the metabolic derangements associated with cancer-bearing states. Indeed, these alterations lead to a pathological state known as cancer cachexia which is, unfortunately, one of the worst effects of malignancy, accounting for nearly a third of cancer deaths. It is characterized by weight loss together with anorexia, weakness, anemia, and asthenia. The complications associated with the appearance of the cachectic syndrome affect both the physiological and biochemical balance of the patient and have effects on the efficiency of the anticancer treatment, resulting in a considerably decreased survival time. At the metabolic level, cachexia is associated with loss of skeletal muscle protein together with a depletion of body lipid stores. The cachectic patient, in addition to having practically no adipose tissue, is basically subject to an important muscle wastage manifested as an excessive nitrogen loss. The metabolic changes are partially mediated by alterations in circulating hormone concentrations (insulin, glucagon, and glucocorticoids in particular) or in their effectiveness. The present study reviews the involvement of different cytokines in the metabolic and physiological alterations associated with tumor burden and cachexia. Among these cytokines, some can be considered as procachectic (such as tumor necrosis factor-alpha), while others having opposite effects can be named as anticachectic cytokines. It is the balance between these two cytokine types that finally seems to have a key role in cancer cachexia.

Cachexia↗
PubMed1979

Cancer cachexia.

Cancer cachexia is characterized clinically by anorexia, early satiety, weight loss. anemia, and marked asthenia. The syndrome is not the result of semistarvation alone but it represents a complex metabolic problem. In the host there are abnormalities in metabolism of energy, carbohydrate, lipid and protein, in water content, in acid-base balance, in electrolyte, mineral and vitamin concentrations, alterations in the activity of host tissue enzymes and changes in endocrine homeostasis and immunologic mechanisms. The cancer initiates and contributes to the genesis of the syndrome but complications of the disease and the treatment may also play a role. Only the control of the cancer can reverse completely the syndrome. It was proposed that cancer peptides throw the host metabolism into a chaotic biochemical state by activating and inactivating host enzymes. This results in increased energy expenditure; the released host metabolites and trapped by the growing cancer.

Animals↗
PubMed1985

Peripheral T-cell lymphoma. A clinical, histologic, and immunologic study of five cases.

The authors describe five white patients with peripheral T-cell lymphoma. Four patients were older than 65 years. All cases presented with a short clinical course and advanced stage at the time of diagnosis. Clinical manifestations included asthenia, weight loss, peripheral and abdominal lymphadenopathy. One case showed tonsillar involvement and subcutaneous lymph node enlargement; hepatomegaly was present in four cases, two of them with splenomegaly. Only one case presented peripheral lymphocytosis and antibodies to human T-leukemia virus. Although three cases were classified as diffuse mixed lymphomas and two as poorly differentiated lymphocytic lymphomas, there were some common characteristics: diffuse infiltration by different proportions of small lymphoid cells and large immunoblasts, some of them multinucleated and similar to Reed-Sternberg cells; accumulation of histiocytes, plasmacytosis, eosinophilia, venular proliferation and compartmentalization were also found. Bone marrow infiltration was observed in two patients. Results of monoclonal markers showed four cases to be OKT4+ and the other OKT8+. The morphologic and immunologic characteristics of these patients were typical and similar to those reported from other geographical areas.

Adult↗
PubMed1988

Age and dose of chemotherapy as major prognostic factors in a trial of adjuvant therapy of osteosarcoma combining two alternating drug combinations and early prophylactic lung irradiation. French Bone Tumor Study Group.

From January 1978 to May 1983, 41 patients with primary high-grade osteogenic osteosarcoma of a limb were treated with a combination of intensive chemotherapy and prophylactic lung irradiation (PLI) intercalated between the first two cycles of chemotherapy. The primary tumor was treated according to its size and location by amputation, resection, high-dose radiotherapy, and salvage amputation for a tumor progressing under radiotherapy. Two weeks after surgery or simultaneously with radiotherapy, a three-drug regimen (cycle A) consisting of mitomycin C on day 1, vincristine followed by a 6-hour infusion of methotrexate on day 2 was given. Folinic acid rescue was started 6 hours after the end of the methotrexate infusion. A PLI of 20 G was given from day 10 to 22. On day 28, a four-drug regimen (cycle B) combining doxorubicin on day 1, vincristine on day 2 and dacarbazine with cyclophosphamide on days 3 to 6 was administered. Thereafter, five additional cycles of A and B were administered provided that the absolute number of polymorphonuclear cells and platelets had recovered. When these values were not attained, treatment was delayed until recovery. After a mean follow-up of 60.6 months, 16 patients have developed distant metastases, associated in four cases with local recurrence. Sixteen patients have died: 15 with metastases, one with no evidence of disease (toxic death). The overall survival of the entire group is 66% and the continuously disease-free survival 58% at 5 years. Alopecia, nausea, vomiting, asthenia, anorexia, and infraclinical and reversible impairment of lung ventilatory function were universal. A noticeable hematologic toxicity also was seen. One toxic death occurred after a pulmonary infection. Two patients developed cardiomyopathy. A multiparametic analysis of prognostic factors shows the very significant influence of age on treatment outcome. The continuous disease-free survival among the 17 patients younger than 15 years is 41% compared to 79% in older patients. The prognostic influence of age was independent of other factors. The delay (for more than two cycles) of methotrexate administration was the second independent prognostic factor. These results raise the question of using different protocols of adjuvant chemotherapy for patients younger or older than 15 years in order to optimize the curability/toxicity ratio.

Adolescent↗
PubMed1993

A phase II study of methotrexate, doxorubicin, cyclophosphamide, and lomustine chemotherapy and lonidamine in advanced non-small cell lung cancer.

BACKGROUND: Combination chemotherapy with conventional antiproliferative drugs is becoming the treatment of choice for patients with advanced non-small cell lung cancer (NSCLC), a good performance status, and no major clinical contraindications. Lonidamine (LND), a new drug with an innovative mechanism of action, might potentiate anticancer activity, without increasing toxicity. METHODS: In a Phase II study, 46 patients with advanced NSCLC were assigned to receive chemotherapy with the methotrexate, doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (MACC) regimen, as originally described, plus LND, 150 mg orally, three times per day. Treatment was continued until progression of disease, occurrence of unacceptable toxic effects, or refusal by the patient (the median duration of MACC treatment was 6 weeks; 7 weeks for LND). RESULTS: For the whole group of patients, actual dose intensities (DI) of MACC and LND were 95% and 67% of those projected (median values), respectively. There was a negative correlation between duration of chemotherapy and the DI of MACC reached in each patient. On the contrary, there was no correlation between the duration of treatment with LND and its DI. The DI of LND and MACC were not correlated with each other. In all, seven objective responses (only partial responses) were observed. The overall median survival time was 42 weeks (confidence limits [CL], 20-52). The median survival length of patients receiving the full dose of LND (450 mg daily for at least 1 week) was 46 weeks (CL, 28-67), as compared with the median survival of 19 weeks (lower CL, 9 weeks) for the remaining patients; this difference was statistically significant (P < 0.05, Breslow test). Toxic effects were as expected with the use of MACC. They were mainly gastrointestinal (any grade of toxicity occurring in 64% of the patients), hematologic (anemia, 44%; leukopenia, 36%; thrombocytopenia, 8%), oral (25%), renal (14%), and cardiac (11%). There was only one treatment-related death, from myocardial infarction and neutropenic sepsis. Uncommon side effects, which were attributed to LND, were mild to moderate and reversible; they included myalgia (26%), asthenia (15%), testicle pain (11%), visual problems (7%), and gastric intolerance (7%). CONCLUSIONS: MACC plus LND is a moderately active regimen in advanced NSCLC, with foreseeable and reversible toxic effects of low-medium grade. Potential enhancements of antitumor activity and possible host survival benefits may be expected by the addition of LND to MACC, but a Phase III study must be performed to identify them.

Aged↗
PubMed2001

Oxaliplatin plus raltitrexed in patients with advanced colorectal carcinoma: results of a Phase I-II trial.

BACKGROUND: Oxaliplatin and raltitrexed both are active anticancer agents in the treatment of patients with advanced colorectal carcinoma: They have different mechanisms of action and toxicity profiles and have shown at least additive effects in experimental and preliminary clinical studies. The aim of this disease oriented Phase I-II study was to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLT), and the objective response rate of this combination in patients with advanced colorectal carcinoma. METHODS: Between April 1998 and March 1999, 69 patients with measurable metastatic colorectal carcinoma who previously were unexposed to palliative chemotherapy were enrolled. In the Phase I part of the study, 27 patients were treated with 3-weekly courses of a fixed dose of raltitrexed (3 mg/m(2) given as a 15-minute intravenous infusion) followed by a 2-hour infusion of oxaliplatin, which was escalated in consecutive cohorts of three to six patients from 85 mg/m(2) to 100 mg/m(2), 120 mg/m(2), 130 mg/m(2), and 140 mg/m(2). After having defined the toxic dose, 42 additional patients were entered at one dose level below to define the therapeutic index of this combination more precisely. RESULTS: In the Phase I part of the study, during the first three dose levels, only one patient each experienced DLT (Grade 3 increase in transaminases, diarrhea, and stomatitis); at level 4, two of the first six patients entered had Grade 3 neutropenic infection or peripheral neurotoxicity, whereas dose level 5 (oxaliplatin 140 mg/m(2)) constituted the toxic dose with three of three patients experiencing DLT (Grade 3 asthenia, transient amaurosis, and diarrhea with Grade 4 neutropenia). Externally reviewed objective responses were noted in 9 of these 27 patients (33%), and stable disease occurred in 12 patients (44.4%). Among the 42 patients who were treated subsequently at the MTD level (Phase II portion), 20 patients (47.6%) responded (95% confidence interval, 32-62.6%), and 21 patients (50%) had stable disease. Their median progression free survival was 9.0 months, and the median overall survival, with 42 patients (67%) currently alive, is > 14.5 months. Treatment tolerance at the MTD was acceptable, with only 9 of 42 patients (21%) experiencing Grade 3-4 neutropenia; Grade 3 nonhematologic adverse reactions included increase in serum transaminases in 6 patients, peripheral neuropathy in 3 patients, diarrhea in 3 patients, and both stomatitis and emesis in only 1 patient each. CONCLUSIONS: The described objective response and toxicity data, which are in agreement with preliminary results of other Phase I-II studies, support the promising therapeutic potential of this combination in the treatment of patients with advanced colorectal carcinoma. Due to its substantial antitumor activity, tolerance (at the recommended MTD level), and convenient 3-weekly outpatient administration schedule, further evaluation of this regimen seems warranted.

Adult↗
PubMed2001

Phase II evaluation of paclitaxel, alpha-interferon, and cis-retinoic acid in advanced renal cell carcinoma.

BACKGROUND: Interferon and 13-cis-retinoic acid (13-CRA) therapy showed clinical response rates of 30% in advanced renal cell carcinoma (RCC). This combination also enhanced sensitivity to paclitaxel in a bcl-2 and mutant p53 expressing renal carcinoma cell line. Based on this, the authors conducted a Phase II clinical trial of the combination of interferon, 13-CRA, and weekly paclitaxel, in advanced RCC. METHODS: The eligibility criteria consisted of unresectable or metastatic RCC, measurable disease, a Southwest Oncology Group performance status of 0-2, and adequate bone marrow, hepatic, and renal function. Prior cytotoxic or immunologic treatment including interferon was permitted. Paclitaxel was administered at a dose of 80 mg/m(2) as a 1-hour intravenous infusion on Days 1, 8, and 15 of each 28-day cycle. Interferon was administered at a dose of 3 million units subcutaneously daily and 13-CRA at 1 mg/kg/day orally in 2 divided doses for the first 21 days of each cycle. RESULTS: Twenty-one patients were enrolled with a median age of 52 years, 16 males and 5 females, 10 patients with no prior therapy, 5 each with prior interleukin-2 or interferon therapy, and 1 patient with both. Four patients had also received prior investigational chemotherapy. A total of 61 cycles were administered with a median of 2 per patient. Grade 3 and 4 toxicities were neutropenia in three patients, anemia in four patients, and asthenia, skin rash, and hypersensitivity reaction in one case each. Of the 20 evaluable patients, one objective partial response was observed for a duration of 7+ months. Seven patients had disease stabilization. The median survival of the entire population was 9.5 months (range, 4-18+ months). CONCLUSIONS: The combination of 13-CRA, interferon, and weekly paclitaxel was well tolerated and had minimal efficacy in advanced RCC.

Adult↗
PubMed2002

Terazosin for benign prostatic hyperplasia.

BACKGROUND: Lower urinary tract symptoms associated with benign prostatic obstruction (BPO) occur in up to 70% of men over the age of 60 years. To relieve these bothersome symptoms, treatment options include alpha-antagonists, also know as alpha-blockers. OBJECTIVES: We conducted a systematic review to evaluate the effectiveness and adverse effects of the alpha-blocker, terazosin, for treatment of urinary symptoms associated with BPO. SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, Cochrane Library), by checking bibliographies, and by contacting manufacturers and researchers. SELECTION CRITERIA: Studies were included if they (1) were randomized trials of at least 1 month duration, and (2) included men with symptomatic BPO and compared terazosin with placebo or active controls. DATA COLLECTION AND ANALYSIS: Study, patient characteristics and outcomes data were extracted in duplicate onto standardized forms utilizing a prospectively developed protocol. The main outcome measure for comparing the effectiveness of terazosin with placebo or other BPO medications was change in urological symptoms as measured by validated symptom scores. Secondary outcomes included urodynamic measures. The main outcome measure for adverse effects was the number of men reporting side effects. We also evaluated the number of men withdrawing from treatment and the number withdrawing due to adverse effects. MAIN RESULTS: 17 studies involving 5,151 subjects met inclusion criteria (placebo-controlled (10); alpha-blockers (7); finasteride alone or in combination with terazosin as well as placebo (1); microwave therapy (TUMT) (1). Study duration ranged from 4-52 weeks. Mean age was 65 years and 82% of men were white. Baseline urologic symptom scale scores and flow rates demonstrated that men had moderate BPO. Efficacy outcomes were rarely reported in a fashion that allowed for data pooling but indicated that terazosin improved symptom scores and flow rates more than placebo or finasteride and similarly to other alpha antagonists. The pooled mean percentage improvements for the Boyarsky symptom score was 37% for terazosin versus 15% for placebo (n=4 studies). The mean percentage improvement for the American Urological Association symptom score (AUA) was 38% compared to 17% and 20% for placebo and finasteride, respectively (n = 2 studies). The pooled mean improvement in the International Prostate Symptom Score (IPSS) (40%) was similar to tamsulosin (43%). Peak urine flow rates improved greater with terazosin (22%), than placebo (11%) and finasteride (15%) but did not differ significantly from the other alpha-blockers. The percentage of men discontinuing terazosin was comparable to men receiving placebo and finasteride but was greater then with other alpha-antagonists. Adverse effects were greater than placebo and included dizziness, asthenia, headache and postural hypotension. REVIEWER'S CONCLUSIONS: The available evidence suggests that terazosin improves urinary symptoms and flow measures associated with BPO. Effectiveness is superior to placebo or finasteride, similar to other alpha-blockers but less than TUMT. Adverse effects were generally mild but more frequent than other alpha-blockers and associated with between a two-four fold increase in treatment discontinuation.

Adrenergic alpha-Antagonists↗
PubMed2004

Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neuromuscular disease characterized by progressive muscle weakness resulting in paralysis, which might be treated with ciliary neurotrophic factor. OBJECTIVES: The objective of this review was to examine the efficacy of ciliary neutrophic factor in amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (searched June 2003) for randomized trials, MEDLINE (from January 1966 to October 2003) and EMBASE (from January 1980 to October 2003), checked the reference lists of papers identified and contacted the authors of studies identified to get additional unpublished results. SELECTION CRITERIA: We considered the following selection criteria: Types of studies: randomized controlled clinical trials; TYPES OF PARTICIPANTS: adults with a diagnosis of either probable or definite amyotrophic lateral sclerosis according to the El Escorial criteria; Types of interventions: treatment with ciliary neurotrophic factor for at least six months, in a placebo-controlled randomized format; Types of outcome measures Primary: survival; Secondary: muscle strength, respiratory function, changes in bulbar functions, changes in quality of life, proportion of patients with adverse side effects (such as cough, asthenia, nausea, anorexia, weight loss and increased salivation). DATA COLLECTION AND ANALYSIS: We identified two randomized trials. The data were extracted and examined independently by the reviewers. Some missing data were obtained from investigators. MAIN RESULTS: Two trials, with a total population of 1,300 amyotrophic lateral sclerosis patients treated with subcutaneous injections of recombinant human ciliary neurotrophic factor, were examined in this review. The methodological quality of these trials was considered adequate. No significant difference was observed between ciliary neurotrophic factor and placebo groups for survival, the primary outcome measure. The relative risk was 1.07 (95% CI 0.81 to 1.41). No significant differences between the groups were observed for most of the secondary outcomes. However, a significant increase of the incidence of several adverse events was noted in groups treated with higher doses of CNTF. REVIEWERS' CONCLUSIONS: Ciliary neurotrophic factor treatment has no effect on amyotrophic lateral sclerosis progression. At high concentration, several side effects were observed. A combination of ciliary neurotrophic factor with other neurotrophic factors (as suggested by results on animal models), and more efficient delivery methods should be tested.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Gallium-67 scintigraphy in macrophagic myofasciitis.

OBJECTIVE: To evaluate gallium-67 (67Ga) uptake and the value of 67Ga scintigraphy for diagnosis of macrophagic myofasciitis (MMF), a recently identified inflammatory myopathy. METHODS: Twelve consecutive patients with MMF confirmed by muscle biopsy, 10 with polymyositis, 10 with sarcoidosis, 8 with fibromyalgia, and 10 with lymphoma without muscle symptoms (serving as normal controls for muscle) were included. Patients received 1.8 MBq 67Ga per kg body weight by intravenous injection, and scintigraphy was performed with a 2-head gamma camera. The various views were acquired for the 3 main photopeaks of 67Ga 48 hours after infusion, and were analyzed in 2 blinded experiments by nuclear physicians. A semiquantitative scale was used to compare the uptake of 67Ga in the vascular soft tissue background with that in the muscles or joints of MMF patients, and with that in the normal controls. RESULTS: The MMF patients (4 men and 8 women, mean +/- SD age 47.8 +/- 8.7 years) had chronic myalgia (n = 11; predominantly in the lower limbs), asthenia (n = 10), arthralgia (n = 7), mild muscle weakness (n = 5), and high serum creatine kinase levels (n = 6). All MMF patients had significantly higher levels of 67Ga uptake in the muscle and para-articular areas than that recorded for the soft tissue background and for the controls. Muscle uptake was bilateral, symmetric, and homogeneous, and predominantly localized in the legs. No linear enhancement corresponding to fascias or synovial involvement was observed. In patients with polymyositis, symmetric, but heterogeneous, 67Ga uptake was observed in muscle, but not in the fascia. In patients with sarcoidosis, 67Ga uptake was nodular and heterogeneous in muscle, was not detected in the fascia, and was suggestive of synovial involvement in the joints. The uptake of 67Ga in fibromyalgic patients was similar to that in normal controls and to that in the soft tissue background. CONCLUSION: MMF is a new condition involving characteristic changes that can be detected by deltoid muscle biopsy. It usually manifests as a weakly specific, chronic arthromyalgic syndrome that predominates in the lower limbs. 67Ga scintigraphy is a noninvasive method that may make it easier to differentiate MMF from fibromyalgia and sarcoidosis.

Adult↗
PubMed1994

Reversal of nephrotic syndrome due to reactive amyloidosis (AA-type) after excision of localized Castleman's disease.

The patient (TAL), a chronic asymptomatic HBV carrier with HBsAg-anti-HBsAg circulating immune complexes, was admitted to our hospital because of a nephrotic syndrome due to renal amyloidosis. There was no family history of hereditary amyloidosis. Recurrent arthralgias, asthenia, and weight loss were the prominent clinical features. Laboratory test results showing that severe chronic inflammatory activity had been present for 6 years. Interleukin-6 (IL-6) serum concentration was 10 times normal and C-reactive protein was 1.9 mg/ml. A complex immunological picture was also present (immune complex formation, exuberant B-cell reactivity, and decrease in the number of CD4 T cells). A localized form of Castleman's disease (CD) (plasma-cell type) was diagnosed by surgical excision of a giant axillary lymph node. AA amyloid was present in the blood vessels. Within 60 days after excision of the mass, the systemic symptoms subsided, laboratory signs of inflammatory activity disappeared and IL-6 serum concentration returned to normal, thus establishing a causal relationship between the localized Castleman's disease, elevated IL-6 concentration and the chronic inflammation responsible for AA amyloidosis. At 10 months of follow-up, the nephrotic syndrome has reversed, kidney function has slowly ameliorated, and the patient has gained 12 kg. Abdominal fat aspirates drawn to search for amyloid, positive before surgery, were subsequently negative. The latter finding, and the remission of the nephrotic syndrome, provided strong evidence for regression of the amyloid deposits. However, the HBsAg-anti-HBsAg immune complexes and depression of T-helper cell activity persist. This immunological derangement is therefore not a consequence of CD. Chronic stimulation of the immune system due to the patient's inability to eliminate HBV, in the contest of perturbed immunity, may have favored the genesis of the lymphadenopathy.

Adult↗
PubMed1979

Creutzfeldt-Jakob disease in France: I. Retrospective study of the Paris area during the ten-year period 1968-1977.

A systematic search for cases of Creutzfeldt-Jakob disease occurring in the ten-year period 1968 through 1977 was conducted in the city of Paris and surrounding departments which comprise the greater Paris area. Fifty-six cases were found among the total population of approximately 10 million inhabitants, with a maximum incidence of 1.1 cases per year per million people in the densely populated city of Paris and a progressively lower incidence in the less heavily populated suburban and rural areas of the region. There was no temporal or geographic clustering of disease. Attention is drawn to the often rapid onset and short duration of illness (nearly two-thirds of the patients died within five months of onset) and the frequent early occurrence of symptoms such as asthenia, diaphoresis, and disturbances of sleep and appetite.

Adult↗
PubMed1996

A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group.

Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.

Adult↗
PubMed2006

Quality of life and psychological status in patients with primary Sjögren's syndrome and sicca symptoms without autoimmune features.

OBJECTIVE: To compare pain, fatigue, and sicca symptoms; quality of life; and psychological status between patients with primary Sjögren's syndrome (SS) and those with sicca symptoms but no autoimmune features (sicca asthenia polyalgia syndrome [SAPS]), and to determine whether a psychological pattern can be detected in patients with SAPS, which could suggest psychological distress as the cause. METHODS: This cross-sectional, prospective study included 111 patients with primary SS according to the American-European Consensus Group criteria and 65 SAPS patients with no focus on lip biopsy and no anti-SSA/SSB antibodies. Pain, fatigue, and sicca symptoms were assessed using visual analog scales; quality of life was assessed using the Short Form 36 (SF-36); and psychological distress by the Symptom Checklist-90-Revised (SCL-90-R) questionnaire. RESULTS: No difference was observed between primary SS and SAPS patients for pain, fatigue, sicca symptoms, quality of life, and psychological status. Fatigue and pain, but not dryness, were correlated with both quality of life and psychological distress in both groups. For primary SS patients, physical and mental composite scores on the SF-36 correlated well with global severity index (GSI) scores of the SCL-90-R (r = -0.29, P = 0.006 and r = -0.61, P < 0.0001, respectively). CONCLUSION: Patients with primary SS and SAPS do not differ in quality of life or psychological status. Although both diseases probably have a different origin, they may require the same psychological support or psychiatric care. The strong correlation between the composite physical and mental scores of the SF-36 and the GSI scores of the SCL-90-R in primary SS patients emphasizes the importance of the psychological dimension in results of the SF-36.

Cross-Sectional Studies↗