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Long-term monotherapy with lamotrigine in newly diagnosed epilepsy in adults.

Lamotrigine (LTG) as both effective against a wide range of seizure types and epileptic syndromes and well tolerated drug is being used in mono--as well as in polytherapy of pharmacoresistant epilepsy. The aim of this study was to evaluate the efficacy, safety and neuropsychological functioning after LTG (mean daily dose: 316 mg) as long-term monotherapy (12 mo) in 24 young adult out-patients (22.5 ys) with newly recognised and not-previously treated epilepsy in an open, non-comparative trial. 67% of patients were responders (above 50% reduction in seizure frequency) and 42% reported seizures remission. The best were results in patients with generalised convulsive fits (87% with remission). Adverse events in the early phase of medication in 21% of patients typically concerned CNS and gastrointestinal system (headache, asthenia, insomnia, nausea, gastric aches) and resolved spontaneously without treatment discontinuation. Biochemical examinations were normal and transient leucopenia and diminishion of MCV were clinically not significant. Neurodynamic abilities, neuropsychological examination results, memory verbal and visual tests and organic evaluation in organic triada tests did not show deterioration after LTG treatment. Slight difficulties in abstractive and operative thinking and some focal symptoms of fronto-temporal origin should be considered a result of drug but also the epilepsy per se. No significant differences in latencies and amplitudes of evoked potentials (VEP, BAEP, SEP and especially ERP-300) were measured after LTG. Preliminary results obtained in this study supported good efficacy and tolerability and especially lack of unfavourable influence of LTG on neuropsychological functioning in young previously untreated patients with epilepsy.

Adolescent↗

[Acute generalized exanthematous pustulosis due to fluconazole].

INTRODUCTION: Fluconazole (Triflucan(R)), a systemic triazole antifungal agent is largely prescribed and some cutaneous side effects have already been described. We report the first case of acute generalized exanthematous pustulosis due to this molecule in a patient with cutaneous candidosis. CASE REPORT: A 65 year-old-woman was treated with fluconazole (200 mg/day) for a persistent cutaneous candidosis infection on the buttocks. After the third dose, the patient presented with a pustular eruption with erythema located on her trunk and in her large skin folds. The eruption was associated with fever at 39 degrees C, asthenia and neutrophilia (9,000/mm(3)). The histologic examination and the negativity of microbiological cultures were consistent with the diagnosis of acute generalized exanthematous pustulosis. The eruption cleared with local steroids in about ten days. Nineteen days later, the same pustular eruption occurred but without fever nor neutrophilia. DISCUSSION: Clinical, biological and histological manifestations were consistent with the diagnosis of acute generalized exanthematous pustulosis due to fluconazole. According to the imputability criteria of Begaud et al., intrinsic imputability of fluconazole was possible (I2). According to the classification of the EuroSCAR study, it was certain. No similar case of recurrence had already been described after the withdrawal of the molecule. We believe this is the first case of acute generalized exanthematous pustulosis due to fluconazole (extrinsic imputability: B0).

Acute Disease↗

[Efficacy and tolerability of long term topiramate in drug resistant epilepsy in adults].

OBJECTIVE: With the objective of evaluating the efficacy and tolerability of topiramate (TPM) in resistant epilepsy, we did a retrospective, open, multicentric analysis of 56 patients aged over 15 years in whom TPM was given as the second, third or fourth drug. All patients had already been on treatment for at least 18 months when topiramate was started. The average follow up was 27.2 months. RESULTS: At the close of the study 16% of the patients were asymptomatic, 23% had a 75% reduction in seizures and 36% a 50% reduction. The drug was withdrawn in 25% of the cases. The adverse effects noted were: nephrolithiasis, asthenia, loss of hair, diarrhoea, weight loss of over 5kg., agitation, aggressiveness, language disorders, ataxia, tremor, somnolence and confusion. The drug had to be suspended when these adverse effects affected the central nervous system moderately or severely, and when there were general effects such as renal calculi in one case and weight loss associated with symptoms which worried the patients in two cases. CONCLUSIONS: Thus, TPM is an effective drug in refractory epilepsy and most patients continue on this treatment. The side effects are typical of the drug, and although there is no risk to life, the patient should be warned of them.

Adolescent↗

Case report: fibroelastoma of the papillary muscle of the mitral valve: diagnostic implications and review of the literature.

A 77-year-old woman was found accidentally to be in atrial fibrillation. Two-dimensional echocardiography revealed the presence of a mass attached to the anterior papillary muscle of the mitral valve. She was mildly symptomatic for dyspnea and asthenia. The patient was successfully operated on to excise the left ventricular mass and preserve the mitral valve apparatus. Morphological examination of the excised tissue led to a diagnosis of papillary fibroelastoma. Surgical treatment must be considered when such a tumor is diagnosed, even though asymptomatic, and especially if left-sided because of the high risk of systemic embolization.

Aged↗

Small bowel metastases of lung cancer as unique metastatic lesions: CT, MRI and small bowel enema findings. a case report.

Small bowel metastases of lung cancer as unique secondary lesions are a very rare occurrence and may be clinically missed due to the aspecificity of the symptoms. Diagnosis is usually made at acute abdominal symptomatology that requires emergency surgical treatment. We report a case of 69-year-old woman, previously treated for epidermoid lung carcinoma, complaining only of aspecific asthenia; blood cell count and chemistry showed a moderate but progressive anemia; no signs of small bowel occlusion were present. The follow-up CT scan showed two large masses at the small bowel level, without any evidence of hepatic, lung, adrenal or brain metastases. MRI and small bowel enema confirmed the presence of the masses, and the diagnosis of small bowel metastases was hypothesized. Surgical specimens of the masses confirmed the radiological suspicion.

Aged↗

The first-reported case of diffuse purulent peritonitis in a patient with retroperitoneal Hodgkin disease (etiopathogenetic hypotheses).

We report a case of purulent diffuse peritonitis in a patient who was affected by Hodgkin lymphoma, with no evidence of other abdominal diseases. This is a 54 y. old. white male who was admitted to our department with a history of asthenia, recurrent fever, dysphagia and abdominal pain. In the plain abdominal radiology pneumoperitoneum was evident. Duodenal perforation suspicion was confirmed by anamnesis and plain radiology which showed the presence of intra abdominal air. Emergency exploratory laparotomy showed a purulent diffuse peritonitis, which relapsed after multiple surgical toilettes and peritoneal lavage. A postoperative abdominal CT scan and histology of a biopsy taken during the second surgical operation showed a retroperitoneal Hodgkin lymphoma, which went to remission after chemotherapy. Considering the two simultaneous clinical manifestations (retroperitoneal Hodgkin lymphoma and peritonitis), we made two pathogenetic hypotheses: a) The retroperitoneal disease produced lymphatic stagnation and peritoneal transudation, which then was infected; b) The abnormal lymph nodes were infected and the abdominal cavity was contaminated from retroperitoneum from blood/lymphatic stream or by contiguity.

Hodgkin Disease↗

[Tolerance of riluzole in a phase IIIb clinical trial].

Within the framework of an early drug access programme launched in 1995, a multicentre open study was initiated in France in order to assess, inter alia, the safety of riluzole (50 mg twice a day) in a total of 2069 patients from 28 centres. This programme, a phase IIIb study with direct individual benefit, had two main objectives: to enable patients to receive riluzole therapy pending regulatory approval and commercial availability and to provide further data on the safety of riluzole in a broader ALS population. The most frequent adverse events related to riluzole treatment were: asthenia, nausea and elevation of serum transaminase levels. These observations, similar to data derived from previous pivotal clinical trials, confirm that riluzole has a satisfactory tolerability profile.

Aged↗

[Mental disorders in patients with complete heart block before and after a pacemaker implantation].

Mental disorders were studied in 52 patients with acquired complete heart block (CHB) before and after pacemaker implantation. Mental state of the patients was characterized primarily by borderline mental pathology--asthenia, affective pathology, hysteria spectrum disorders with autonomic symptoms and hypochondriac disorders. The structure and expression of mental disorders depend on premorbid personality traits of the patients, duration, severity and stage of the disease, the phase in respect to surgery intervention as well as preoperative period duration. Being the main therapy method, the operative CHB treatment, in general, positively influences the dynamics of mental disorders. However, in some cases, pacemaker implantation changes the behavior and quality of life of patients. Peculiarities of mental disorders in the CHB demand to include of psychopharmacotherapy and psychotherapy in treatment process.

Aged↗

Docetaxel in the treatment of ovarian cancer.

Docetaxel (Taxotere) has extended the armamentarium of agents with significant activity in the treatment of ovarian cancer. As a single agent in advanced ovarian cancer patients previously treated with a platinum agent, docetaxel at 100 mg/m2 every 3 weeks yields a 30% overall response rate and a 6-month duration of response. In vitro data demonstrate a lack of complete cross-resistance between docetaxel and paclitaxel. As a result, antitumor activity has also been demonstrated in patients refractory to a paclitaxel-containing regimen. In both platinum- and paclitaxel-pretreated patients, the highest response rates were obtained in patients with the longest interval of time since receipt of prior chemotherapy. Docetaxel has been successfully combined with the platinum salts for the first-line treatment of ovarian cancer patients. In combination with cisplatin, response rates of 69% were reported. In an effort to minimize hematologic toxicities and asthenia associated with the cisplatin/docetaxel combination, investigators have substituted carboplatin (Paraplatin) for cisplatin. Several phase II studies and the Scottish Randomized Trial in Ovarian Cancer (SCOTROC), a large phase III randomized trial, of the docetaxel/ carboplatin combination have been completed. The most frequent toxicity noted is neutropenia, which is generally of brief duration, predictable, and manageable. The docetaxel/carboplatin combination has a notably low rate of neurotoxicity. Therefore, the SCOTROC comparative trial, demonstrating equivalent overall response rates and progression-free survival rates, suggests that the docetaxel/carboplatin combination may represent a new alternative to paclitaxel/carboplatin as first-line chemotherapy for advanced ovarian cancer.

Antineoplastic Agents, Phytogenic↗

[Gluteal fistulo-gummatous syndrome (malignant dysembryoma)].

The authors present the case of a 61 years old patient with fistulo-gummutous lesions with ulcer formation and pus formation in the right buttock, loss of weight and asthenia. The lesions appeared six months after a violent blow on the right buttock. General examination of the ano-rectal region, including sigmoidoscopy and fistulography, together with histo-pathological examination, revealed the existence of a perirectal muciparous carcinoma developing on embryonic glanduilform remains, situated in the right perinee-rectal region. The special interest of this case resides in its rareness and the unusual clinical appearance of gummatous fistula.

Buttocks↗

[ANTI HCV PREVALENCE IN CIRRHOTIC PATIENTS]

We studied 30 patients with diagnosis of liver cirrhosis (clinical, biochemical, pathologyc and images diagnosis); each patients was evaluated for hepatitis C antbodies (Elisa 2rd/3rd generation) and 27 patients were evaluated for hepatitis B surface antigen. The most characteristic symptoms and signs were ascitis (60%), anorexia (63.65%) and asthenia (66.65%). Hypo albuminemia in 82% of cases; 65.5% with serum aminotransferasas high level; 84% with trombocytopenia. Two patients were positive of hepatitis C antiboides (6.65%) and two patients olso were hepatitis B surface antigen positive. One patients was positive for anti-HVC and HBsAg.

Journal Article↗

[Secondary recurrent hepatitis in ventricular arrhythmia].

INTRODUCTION: A major episode of hepatic cytolysis, rapidly regressive and occasionally recurrent, evokes a bilary or toxic pathology. We report an exceptional case in which several episodes of cytolysis were secondary to a paroxystic cardiac rhythm disorder. OBSERVATION: A 44 year-old woman was hospitalized 3 times during 4 months for episodes of asthenia and rapidly regressive cytolysis. Lithiasic, viral, metabolic, autoimmune and toxic causes were eliminated. A cardiac rhythm disorder was revealed during the last two episodes and diagnosis was made of intermittent and asymptomatic ventricular tachycardia, secondary to arryhthmogenic right ventricular dysplasia, and was confirmed on the electrocardiogram, cardiac scan and magnetic resonance imaging. Treatment of the cardiac rhythm led to the absence of further relapse. COMMENTS: In our patient, the clinical and chronological imputability appeared highly probable. The responsibility of perturbed cardiac rhythm in the genesis of an ischemic hepatopathy is classical, but little documented. Our observation confirms that severe unexplained cytolysis requires systematic search for a cardiac rhythm disorder, even in the absence of a known or symptomatic cardiopathy.

Adult↗

Pfeifer-Weber-Christian's panniculitis in an obese patient with antinuclear antibody-positive leukocytoclastic vasculitis.

Pfeifer-Weber-Christian's panniculitis is a rare syndrome characterized by fever, arthralgias, fatigue and recurrent nodular panniculitis. It has been associated with pancreatic diseases, trauma, connective tissue diseases, alpha-1-antitrypsin deficiency, systemic lupus erythematosus, infections, lymphoproliferative diseases and neoplasias. We report the case of a 43-year-old obese male patient who presented with asthenia, arthralgias, intermittent fever, skin erythema and a large hard-elastic tumor of the right calf. Laboratory analysis revealed increased values of the immunophlogosis parameters and positivity for serum antinuclear antibodies. Surgical drainage of the abscess-like tumor mass, revealed leakage of a sterile, subflavious, oily and thick liquid; a skin biopsy showed intra and perivascular infiltration by neutrophils, diagnostic for leukocytoclastic vasculitis. Treatment with prednisone induced clinical improvement and normalization of the laboratory data. The clinical picture, laboratory data and efficacy of prednisone therapy confirmed that the patient developed Pfeifer-Weber-Christian's panniculitis in the clinical setting of an antinuclear antibody-positive leukocytoclastic vasculitis.

Adult↗

Clinical benefit of gemcitabine-cisplatin in advanced non-small cell lung cancer elderly patients.

BACKGROUND: Cisplatin-based chemotherapy seems to improve the control of non-small cell lung cancer (NSCLC)-related symptoms, but assessment of symptomatic gain in these patients is often difficult. This study was designed to test a method for the assessment of clinical benefit in elderly advanced NSCLC patients, after weekly cisplatin-gemcitabine chemotherapy. PATIENTS AND METHODS: Evaluation of clinical benefit was the primary end-point. Clinical benefit derived from the evaluation of eight parameters: PS, cough, dyspnea, pain and hemoptysis were considered primary parameters. Weight loss, asthenia and anorexia were secondary parameters. RESULTS: Twenty-nine patients aged > 65 years, symptomatic at study entry, were enrolled. Responses were calculated according to the intent-to treat principle. Fifteen patients were considered as clinical benefit responders for an overall clinical benefit response rate of 52% (95% C.I. = 33.5% to 70%). The median duration of clinical benefit was 9 months (range 2-36). Tumour objective responses, according to WHO criteria, were 14, for an overall response rate of 48% (95% C.I. = 31% to 65%). Ten patients (34%) obtained both clinical benefit and tumour response. The median survival-time was 10 months (range 1-36). Chemotherapy was well-tolerated with low incidence of WHO grade III-IV toxicities. CONCLUSION: Evaluation of clinical benefit in advanced, symptomatic, elderly NSCLC patients is feasible and could be used together with tumor response and quality of life questionnaires to assess the efficacy of chemotherapy. It could reasonably be extended to non-elderly NSCLC patients. Our results suggest that weekly cisplatin-gemcitabine seems to be able to improve the principal NSCLC-related symptoms in elderly patients.

Aged↗

[HUMAN BALANTYDIASIS IN HUARAZ: REPORT OF FIVE CASES]

In order to know the clinical behavior of Human Balantidiasis, five symptomatic cases are reported (three from hospital and two from private practice), observed from December 1993 to December 1996 in the city of Huaraz (3,100 Mt above sea level). All patients were from Ancash, being their mean age 57,2 years old (3-85); 4/5 were male, and 3/5 were farmers. They bred pigs, lived in a rural environment and had no access to drinking water nor to sewage at home. The mean length of this disease was 22,8 days (10-60). Clinical symptoms were dysenteric diarrhea and abdominal pain accompanied by fever, pallor, asthenia, weight loss and dehydration. All five cases presented the parasite in the feces: one as a cyst, two as trophozolte, and the other two, both shapes. Two patients suffered serious complications: The first one had intestinal perforation, peritonitis and died, and the other one presented bronchopneumonia, low digestive hemorrhage and sepsis. Treatment included tetracycline, metronidazole and large spectrum antibiotic, if required. When we observe a patient with hemorrhagic or chronic severe diarrhea in Huaraz, who comes from the rural area and is a breeder of pigs, we must consider a diagnosis based on Human Balantidiasis.

Journal Article↗

Results of a Phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies.

SU5416 is a small molecule antiangiogenic agent that inhibits vascular endothelial growth factor (VEGF) stimulation of the KDR tyrosine kinase receptor. In this Phase I dose escalation trial, a weekly dose schedule of SU5416 was tested whereby an initial 5-day loading dose was followed by weekly maintenance infusions. The start dose was 20 mg/m(2) for the loading dose followed by 65 mg/m(2) for the weekly infusions. Dose escalations occurred at 33% until a final dose of 65 mg/m(2) (loading dose) and 190 mg/m(2) (weekly infusion) was obtained. Twenty-two patients were treated at five dose levels; tumor types included gastrointestinal (8), breast (3), lung (4), sarcoma (2), and other (5). The most common serious drug-related toxicity was headache, often associated with nausea and vomiting. Grade 1 and 2 toxicities included headache, nausea, vomiting, asthenia, pain at the infusion site, phlebitis, change in voice, and fevers. Of 19 evaluable patients, 4 obtained clinical benefit as defined by tumor regression (1) or disease stabilization for at least 12 weeks (3). Pharmacokinetic data revealed that the weekly infusion schedule prevented the reported 50-60% induction in SU5416 clearance observed with either daily or twice weekly dosing. Higher baseline levels of urine VEGF were observed in the 4 patients who gained clinical benefit, suggesting this may be a useful marker for predicting response to anti-VEGF therapies. Our results suggest that a weekly schedule of SU5416 shows signs of biological activity and is well tolerated at doses up to 145 mg/m(2).

Adult↗

3-month contraceptive injection approved.

FDA has approved medroxyprogesterone acetate as Depo Provera Contraceptive Injection, effective for 3 months in preventing pregnancy in women. In clinical studies, the drug's failure rate was less than 1%. However, physicians must ensure that patients receive injections on schedule to prevent pregnancy. The recommended dose is 150 mg administered every 3 months by deep, intramuscular injection in the gluteal or deltoid muscle. Most women in clinical studies of Depo Provera experienced menstrual irregularities. As use continued, amenorrhea became common, reported by 57% of the women by the end of a year of treatment. Other side effects included weight gain, headache, nervousness, abdominal pain or discomfort, dizziness, and asthenia. Physicians should administer the drug only to women found not to be pregnant, because fetal exposure may lead to low birth weight and other problems. Recent data have demonstrated that longterm use may contribute to osteoporosis, and the drug's manufacturer, the Upjohn Company of Kalamazoo, Michigan, will conduct additional research to study this possible side effect. Contraindications are similar to those for other contraceptives and include undiagnosed vaginal bleeding, known or suspected malignancy of breast, thromboembolic disorders, cerebral vascular disease, and liver dysfunction. Depo Provera was developed in the 1960s and has been approved for contraception in many other countries. When FDA first reviewed data on the drug in the 1970s, animal studies raised questions about its potential to cause breast cancer. Since then, longterm controlled clinical studies in other countries have shown a risk of breast cancer comparable to oral contraceptives, and no increased risk for ovarian, liver, or cervical cancer. The studies also showed that the contraceptive injection reduced the risk of endometrial cancer. FDA approved the drug October 29, 1992.

Contraception↗

[Anaphylactic shock revealing anisakiasis].

INTRODUCTION: The manifestations of anisakiasis are essentially digestive pain, nausea or transit disorders. When it is initially asymptomatic, it is later revealed by a major complication, which is occlusion on an eosinophilic granuloma of the ileum. Over the past 5 years, the international literature has reported allergic manifestations related to this helminthozoonose, such as urticaria, angioedema, bronchospasm and occasionally anaphylactic shock. OBSERVATION: A 60 year-old man presented with an anaphylactic shock and diarrhea. One month later, he exhibited persisting asthenia, cough and intermittant pruriginous rashes. Blood hypereosinophilia was borderline and total IgE was clearly increased. The initial event was retrospectively labeled "histaminic shock following ingestion of tuna fish". The discovery of highly positive anisakiasis serology, conducted simultaneously in 2 different laboratories, corrected the diagnosis. The patient was treated with albendazole (10 mg/kg/day for 7 days) with excellent results on the clinical and biological symptomatology. CONCLUSION: With the occurrence of an allergic reaction, whether major or minor, a notion of ingestion of fresh fish must be searched for and, if positive, an immunodiagnosis of anisakiasis must be requested. Any seriological positivity should be controled by gastro-duodenal endoscopy. If the search for larvae is negative, we recommend anthelminthic treatment as a precaution.

Albendazole↗