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PubMed2006

Ifosfamide neurotoxicity: an atypical presentation with psychiatric manifestations.

Ifosfamide can be responsible for acute central neurotoxicity in children and adolescents treated for cancer. The signs of acute encephalopathy most frequently observed are: alteration of consciousness, cerebellar syndrome, asthenia, urinary incontinence, cranial nerve palsy, and seizures. Various combinations of these signs may occur, but disorders of consciousness and drowsiness are common. We describe the case of a young man presenting with reversible acute hypomanic disorder during ifosfamide-based chemotherapy and discuss the possible mechanisms of this toxicity.

Acute Disease↗
PubMed2007

Acenocoumarol and vasculitis: a case report.

A 62-year-old woman was referred to the dermatology department for a history of fever, asthenia and cutaneous rash, which appeared after a 3-day course of digitalin and acenocoumarol for atrial fibrillation. The physical examination revealed multiple round confluent purpuric lesions over her entire legs with no blistering. Laboratory exams were all negative. Biopsy of the involved skin was compatible with leucocytoclastic vasculitis. The acenocoumarol treatment was withheld and the skin lesions resolved spontaneously over the next 10 days. The cause of this purpura was seemingly acenocoumarol because of the close temporal relationship between exposure to the drug and the onset of the symptoms, and the spontaneous resolution of the lesions after acenocoumarol was discontinued. This observation illustrates a rare association between vasculitis and acenocoumarol. Clinicians should be aware of this potential adverse effect and recommend interrupting the drug intake when temporal relation is evocative.

Acenocoumarol↗
PubMed1990

Efficacy of once-a-day terazosin in benign prostatic hyperplasia: a randomized, double-blind placebo-controlled clinical trial.

This randomized, placebo-controlled, double-blind study was performed to evaluate the efficacy and safety of once-a-day terazosin (10 mg/day) in ambulatory patients (n = 57) with benign prostatic hyperplasia (BPH). After a 4-week placebo lead-in and a 24-week treatment period with terazosin (both single-blind), 30 patients who responded to terazosin were randomly assigned to either the terazosin or placebo treatment group for 12 weeks. During the single-blind treatment period, the peak urine flow rate increased 54% from a baseline average of 7.76 ml/sec to 11.92 ml/sec after terazosin; the mean flow rate increased 55% from a baseline of 4.90 ml/sec to 7.59 ml/sec; and the residual volume decreased 56% from 93.1 ml to 40.7 ml. The mean obstructive symptom score, irritative symptom score and physician's global assessment score improved by 68%, 34% and 27%, respectively. All these changes were significant (P less than 0.05) when compared to baseline values. During the double-blind period, the improvement in all the variables was sustained in the terazosin group but not in the placebo group. Peak and mean urinary flow rates, and physician's global assessment showed significant (P less than or equal to 0.05) differences at the end of the double-blind period. Adverse events occurred only during the single-blind period. The most frequent were headache (n = 6), asthenia (n = 3), and hypotension (n = 3). In summary, terazosin administered once-a-day improved the obstructive and irritative symptoms of BPH, urine flow rates and residual volume. Terazosin was well tolerated.

Adrenergic alpha-Antagonists↗
PubMed2007

Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice.

Rhodiola rosea L., or 'golden root', is a popular plant in traditional medicine in Eastern Europe and Asia, with a reputation for improving depression, enhancing work performance, eliminating fatigue and treating symptoms of asthenia subsequent to intense physical and psychological stress. Due to these therapeutic properties, R. rosea is considered to be one of the most active adaptogenic drugs. To confirm and extend results obtained in the few preclinical and clinical studies available in English language journals, the purpose of the present study was to re-investigate the effects produced by a single oral administration of an R. rosea hydroalcohol extract (containing 3% rosavin and 1% salidroside) on the central nervous system in mice. The extract was tested on antidepressant, adaptogenic, anxiolytic, nociceptive and locomotor activities at doses of 10, 15 and 20 mg/kg, using predictive behavioural tests and animal models. The results show that this R. rosea extract significantly, but not dose-dependently, induced antidepressant-like, adaptogenic, anxiolytic-like and stimulating effects in mice. This study thus provides evidence of the efficacy of R. rosea extracts after a single administration, and confirms many preclinical and clinical studies indicating the adaptogenic and stimulating effects of such R. rosea extracts. Moreover, antidepressant-like and anxiolytic-like activities of R. rosea were shown in mice for the first time.

Administration, Oral↗
PubMed1998

Immunogenicity and safety in adults of a new chromatographically purified Vero-cell rabies vaccine (CPRV): a randomized, double-blind trial with purified Vero-cell rabies vaccine (PVRV).

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (Verorab; Pasteur Mérieux Connaught). The immunogenicity and safety of primary immunization, followed by a booster at one year, with CPRV was compared to that of the purified Vero cell vaccine (PVRV) in a randomized, double-blind study carried out at four veterinary schools in France. A total of 330 healthy, male and female, first-year veterinary students, aged at least 18 years and who required pre-exposure rabies prophylaxis, were enrolled in this study. Included subjects were randomly assigned either CPRV (n = 163) or PVRV (n = 167) to be given as a primary immunization series of three intramuscular injections (D0, D7, D28), followed by a booster after 1 year (D365). Blood samples for serological analysis were taken at D0 (before first injection), D28, D42, D180, D365 (before booster) and D379. All subjects developed a strong immune response to the primary series, and at D42, all subjects had seroconverted for rabies neutralizing antibody (serum titre > or = 0.5 IU/ml). The rabies virus-neutralizing antibody GMT value at D42 in the CPRV group (23.0 IU/ml) was non-inferior to that in the PVRV group (29.6 IU/ml), according to a one-sided non-inferiority test. While antibody titres tended to decrease over the period of follow-up, at D365 (before booster), 97.5% subjects in the CPRV group and 98.8% of subjects in the PVRV group remained seroconverted. After booster, although the rabies antibody GMT value in the CPRV group was lower than that in the PVRV group, all subjects in both groups were seroconverted, and the difference is probably not clinically important. The incidence of local and systemic reactions tended to decrease with each dose during the primary immunization series, followed by a slight increase after booster (significant time-effect in an exploratory logistic regression analysis). Although mild or moderate local reactions tended to be more frequent after injection with CPRV compared to PVRV, systemic reactions were reported less often (significant group-effects in exploratory logistic regression analyses). One serious adverse event possibly related to vaccine occurred during this study (severe asthenia after the third dose of PVRV). This comparative study in healthy young adults demonstrates that the new chromatographically purified rabies vaccine is as immunogenic as PVRV, and seems to be associated with fewer systemic reactions.

Adolescent↗
PubMed1999

Phase II trial of vinorelbine in recurrent and progressive epithelial ovarian cancer.

OBJECTIVE: A phase II, multicenter trial was conducted to define the efficacy and safety of vinorelbine (Navelbine (vinorelbine tartrate) injection, NVB) in the treatment of advanced epithelial ovarian cancer (EOC). METHODS: Patients with persistent or recurrent EOC who had received one prior platinum-based chemotherapy regimen were eligible. NVB was administered at 30 mg/m2 as a weekly outpatient intravenous infusion. RESULTS: Using an intent-to-treat analysis of the 38 patients who received at least one dose, 11(29%, 95% confidence limits 15-46%) objective responses (4 complete, 7 partial) were observed. The median duration of response was 19 weeks. For all 38 patients, the median time to treatment failure and median survival were 12 and 60 weeks, respectively. Four of the 12 patients with platinum-resistant disease responded, while 7 of the 24 patients with platinum-sensitive disease responded. Toxicity was evaluable in all 38 patients. During course 1, 15 patients required dose reduction and 21 required dose delays. Grade 3-4 granulocytopenia occurred in 23 (62%) of 37 reporting patients. Grade 3-4 anemia and thrombocytopenia occurred in 16 and 5%, respectively. The most common nonhematologic toxicities were nausea (grade 3 or less, in 34%), constipation (grade 3 or less, in 29%), and asthenia (grade 2 or less, in 24%). No life-threatening adverse effects were reported. CONCLUSIONS: NVB is an effective, palliative agent for women with recurrent EOC. Dose-limiting granulocytopenia is substantial, yet manageable.

Adult↗
PubMed2006

Cytokines as mediators and targets for cancer cachexia.

The cachexia syndrome, characterized by a marked weight loss, anorexia, asthenia and anaemia, is invariably associated with the growth of a tumour and leads to a malnutrition status caused by the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumour and the host results in a state of accelerated catabolism, which promotes severe metabolic disturbances in the patient. The search for the cachectic factor(s) started a long time ago, and many scientific and economic efforts have been devoted to its discovery, but we are still a long way from a complete answer. The present review aims to evaluate the different molecular mechanisms and catabolic mediators (both humoural and tumoural) that are involved in cancer cachexia and to discuss their potential as targets for future clinical investigations.

Cachexia↗
PubMed1980

Vindesine: a new vinca alkaloid.

Vindesine (VDS) is an analogue of the vinca alkaloids. Its spectrum of antitumoral activity is similar to that of vincristine (VCR), but with milder experimental neurotoxicity, and it inhibits the polymerization of tubulin. Its terminal half-life is 24 h and its plasma clearance is intermediate between those of vinblastine (VLB) and VCR. The maximal tolerated dose is 4-5 mg/m2/week, the dose-limiting toxicity being myelosuppression (nadir by days 7-8 and recovery by days 11-13). It has already been demonstrated as efficient in childhood acute lymphoid leukemia (ALL), non-Hodgkin's lymphoma, blastic crisis of chronic myeloid leukemia, and esophageal carcinoma. It has also shown activity in Hodgkin's disease, breast and germ cell carcinomas, and melanoma. Intolerance is mainly neurologic, with paresthesias, without motor impairment, or hematologic, with leukopenia, and sometimes alopecia, asthenia, and muscle pains. The results are better if the patients have not been treated previously; continuous infusion could be of interest and there appears to be no cross-resistance with its parent VCR, as documented in ALL.

Animals↗
PubMed1996

Investigation of a Q-fever outbreak in northern Italy.

OBJECTIVES: A study was conducted to evaluate the extent of a Q-fever epidemic through active case finding in the area of Vicenza (north-eastern Italy), and to identify risk factors for Q-fever in this outbreak. METHODS: 1) Descriptive epidemiology; 2) Seroepidemiological survey; 3) Case-control study. 1) Epidemic curve and maps with the location of cases. Identification of the road followed by the flocks of sheep. 2) Cross-sectional study on humans and flocks of sheep tested for anti-Coxiella burnetii antibodies. 3) Cases were defined by the presence of fever > 38 degrees C plus serological confirmation. Controls were 94 apparently healthy individuals attending outpatient facilities for control visits or certification, group-matched by geographical area, age and gender. A standardized questionnaire was administered by trained interviewers. Odds ratio and 95% confidence intervals (CI) were used to evaluate risk factors for Q-fever. RESULTS: A total 58 cases were identified in a 5-month period. Male to female ratio was 2.8:1; mean age was 42 years (range: 20-65 years). Twenty-eight patients (48%) were hospitalized. Fever was accompanied by asthenia (81%), headache (76%), chills (72%), and myalgia and arthralgia (53%); cough was present in 47% of patients. Rx abnormalities were found in 81% of the patients undergoing chest X-ray. Among 111 apparently healthy family members who underwent serological testing, four (3.6%) had antibodies to Coxiella burnetii. Three flocks which passed through the outbreak area between late May and early June were shown to be infected, with prevalence of antibodies ranging between 45 and 53%. The case-control study showed a significant association with exposure to flocks of sheep (Odds ratio = 6.1; 95% CI 2.5, 16.3). Other potential risk factors were not more commonly reported by cases with respect to controls. CONCLUSIONS: Indirect exposure to flocks of sheep was a determinant of this outbreak of Q-fever. This finding suggests that transmission occurred through inhalation of contaminated airborne particles. The importance of control measures should be stressed in areas traversed by flocks of sheep.

Adult↗
PubMed1996

Community outbreak of acute respiratory infection by Mycoplasma pneumoniae.

We present the results of the investigation of an epidemic outbreak of Mycoplasma pneumoniae infection which affected 95 schoolchildren from certain village in Catalonia. The investigation took an epidemiological, clinical and microbiological approach, detecting by capture enzyme-immunoassay technique the presence of IgM antibodies against M. pneumoniae. All cases occurred over a 9 week period. The attack rate in children under five was 18% and 8.2% in those from 5-14 years. The age mean and standard deviation of the cases was 5.2 +/- 3.5 years, the range being from 9 months to 14 years. Cough was the most common clinical manifestation (87.4%), followed by fever (67.4%), asthenia (21.1%), abdominal pain (18.9%), vomiting (13.7%), earache (8.4%) and sore throat (6.3%). There was no significant difference in the distribution of symptoms according to age groups. IgM anti M. pneumoniae was positive in 36 (37.9%) of the samples analysed. Treatment chosen in most cases (90) was eritromicin and there was a correct evolution in all cases except for two clinical and radiological recurrences. Hospitalization was only necessary in 5 cases. The present findings are important to emphasize the high incidence of M. pneumoniae respiratory disease in children under 5, and suggests that with respiratory processes affecting very young children, a possible Mycoplasma pneumoniae infection should also be considered and the necessary action taken in the form of early and appropriate treatment.

Adolescent↗
PubMed1993

Hepatic mesenchymal sarcoma: MRI findings.

Hepatic undifferentiated mesenchymal sarcoma is a rare pediatric malignant neoplasm. We present three children, aged 7, 8, and 12 years, with this tumor. Clinical presentation was abdominal pain, palpable mass, asthenia, anorexia, and weight loss. One had jaundice. All three lesions were detected on ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). MRI localized the lesions more accurately than the other methods, with good resectability correlation. On MRI, these tumors were markedly hyperintense on long TR/TE spin-echo (SE) and short-time inversion recovery (STIR) sequences. This was due to the cystic areas with myxoid material and necrosis. The internal separations were hypointense on these sequences. On short TR/TE SE sequences the lesions presented a fibrous pseudocapsule (two cases), and internal hyperintense areas representing hemorrhage (two cases). MRI also detected vascular invasion (one case), biliary obstruction (one case), and hilar adenopathies (one case). The combination of hemorrhage (hyperintense on short TR/TE SE) and cystic or myxoid components (markedly hyperintense on long TR/TE SE and STIR sequences) is common in this tumor.

Child↗
PubMed1982

VM26 in malignant hematological diseases. A phase II study.

From August 1979 to April 1981, 33 consecutive patients with malignant hematological diseases, entered this phase II study. Sixteen patients had NHL, eight CLL, four Myeloma, three HD, one ALL, and one Polycythaemia vera. Two patients were unevaluable because of early death. The median age was 67 years. Eight patients were not pretreated with drugs. Two CR (5+, 20+ weeks) were obtained among NHL patients, whereas five PR were observed among two NHL, one CLL, one Myeloma, and one HD patients, respectively. Toxicity was almost exclusively hematologic and occurred in ten patients, in one of them causing severe myelosuppression. Moreover, severe asthenia, attributable to VM26, was encountered in three patients, in one requiring the suspension of the treatment.

Drug Evaluation↗
PubMed1980

A peculiar case of malignant cerebral reticulosis: clinico-pathological study.

A man aged 56 years, previously healthy, developed asthenia, hypersonnia, apathy, later polydipsia and bulimia, headache and episodes of unconsciousness. There was temporary improvement with steriod therapy, but ever-deepening stupor appeared till death due to bronchopneumonia. All blood chemistry examinations were normal. The CSF IgG was elevated but no neoplastic cells were seen. At autopsy areas of grayish color in the basal gagnlia and granulomatous tissue in the floor of the third ventricle and in the mamillary bodies were seen, and the gonads were attrophied. Microscopically, in the floor of third ventricle, mamillary bodies and adjacent leptomeninges there was granulomatous tissue made up of more-or-less typical cells of the reticulum, polymorphonuclear cells, plasma cells and some phagocytes along with proliferation of small blood vessels and reticulin fibers. In addition, the white matter of the frontal lobes, pons, middle cerebellar peduncle and cerebellar white matter contained diffuse proliferation of pleomorphic histiocytic elements with questionable atypical mitoses. Notwithstanding, the morphology of our case suggests that it is a peculiar form of malignant reticulosis (or malignant histocytosis) related to histiocytosis X. The duplicity of the features of our case suggests it to be neoplastic, where the proliferative phase is followed by a granulomatous and sclerotic one.

Brain Neoplasms↗
PubMed1987

Chronic intracranial hypertension secondary to neurobrucellosis.

Chronic intracranial hypertension in the presence of hydrocephalus and/or arachnoiditis is a rare presentation of neurobrucellosis. The present case is exceptional because neither hydrocephalus nor arachnoiditis were present. Brucellosis was diagnosed by serological tests. The patient developed asthenia, anorexia, weight loss, violent headaches, explosive vomiting, bilateral papilloedema, diplopia with paralysis of the abducens nerves, left supranuclear facial paralysis and left hemiparesis. A skull radiograph showed destruction of the sella turcica. Rapid recovery was attained with the use of antibiotics. The pathogenesis of this intracranial hypertension syndrome with destruction of sella turcica is discussed.

Brucellosis↗
PubMed1991

Phase II trial of carboplatin or iproplatin in cervical cancer.

From July 1984 to November 1987, 89 patients with recurrent measurable squamous-cell cancer of the uterine cervix were randomized in a single institution to receive treatment with either carboplatin (CBDCA) or iproplatin (CHIP). Objective response rates were similar: 2 complete regressions (CRs) and 10 partial regressions (PRs) were recorded both in the 46 evaluable patients treated with CBDCA (response rate, 26.1%; 95% confidence interval, 15-41%) and in the 40 evaluable patients treated with CHIP (response rate, 30%; 95% confidence interval, 17-47%). The median duration of response was 5.5 months for CBDCA and 6 months for CHIP; the median survival was 7.5 and 7.6 months, respectively. Both drugs were given in an outpatient setting and myelosuppression (thrombocytopenia) was the predominant toxicity. Analysis of all toxic events yielded additional interesting observations: the occurrence of moderate to severe platelet nadirs beyond cycle 1 was confined to CHIP, a higher incidence of gastrointestinal toxicity during treatment with CHIP, and five moderate to severe complaints of asthenia (recorded as neurologic events) during CHIP therapy versus only one during treatment with CBDCA. Because of its antitumor activity and its toxicologic advantage, a future role for CBDCA in the treatment of cervical cancer appears likely.

Antineoplastic Agents↗
PubMed1994

Epidemiologic approach to human toxocariasis in western France.

Toxocara canis is a common parasite in puppies. The danger to human health has not been properly established. We estimated the current incidence of this pathogen in two western districts of France, Loire-Atlantique and Maine et Loire. Blood samples from 1836 eosino-philic patients were collected and tested by an enzyme-linked immunosorbent assay (ELISA) excretory-secretory Toxocara antigen test. We obtained positive results in 22% of the cases and highly positive results in 7%. The ELISA data seemed to be age-dependent, with older patients having more positive results (P < 0.0001). The interlaboratory distribution of positive test results was statistically significantly different (P < 0.0001), suggesting regional sources. The main clinical expressions of toxocariasis were: asthenia, gastric pain, and pulmonary disease. Individual and collective surveys of this zoonotic disease need to be carried out.

Animals↗
PubMed1997

Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin.

Experimental data have suggested that the pineal hormone melatonin (MLT) may counteract chemotherapy-induced myelosuppression and immunosuppression. In addition, MLT has been shown to inhibit the production of free radicals, which play a part in mediating the toxicity of chemotherapy. A study was therefore performed in an attempt to evaluate the influence of MLT on chemotherapy toxicity. The study involved 80 patients with metastatic solid tumors who were in poor clinical condition (lung cancer: 35; breast cancer: 31; gastrointestinal tract tumors: 14). Lung cancer patients were treated with cisplatin and etoposide, breast cancer patients with mitoxantrone, and gastrointestinal tract tumor patients with 5-fluorouracil plus folates. Patients were randomised to receive chemotherapy alone or chemotherapy plus MLT (20 mg/day p.o. in the evening). Thrombocytopenia was significantly less frequent in patients concomitantly treated with MLT. Malaise and asthenia were also significantly less frequent in patients receiving MLT. Finally, stomatitis and neuropathy were less frequent in the MLT group, albeit without statistically significant differences. Alopecia and vomiting were not influenced by MLT. This pilot study seems to suggest that the concomitant administration of the pineal hormone MLT during chemotherapy may prevent some chemotherapy-induced side-effects, particularly myelosuppression and neuropathy. Evaluation of the impact of MLT on chemotherapy efficacy will be the aim of future clinical investigations.

Adult↗
PubMed1987

Cardiomegaly and abdominal mass in an acromegalic patient.

We herein report the case of a 53-year-old white acromegalic patient with an abdominal mass due to massive cardiomegaly. The patient suffered from long lasting acromegaly refractary to bromocriptine, transsphenoidal surgery and radiotherapy. He had been previously diagnosed as having systemic hypertension, ischemic chest pain and congestive heart failure with marked cardiomegaly. The present admission was due to asthenia, anorexia and weight loss that were finally attributed to adrenal insufficiency secondary to radiotherapy. Plain abdomen X-ray suggested the presence of supramesocolic mass. A large cold area in the left hepatic lobe was detected on the radionuclide liver scan. Radionuclide angiography surprisingly identified the cold area as a vascular structure corresponding to the heart. A body CT scan revealed the heart was expanding between stomach and liver. Two-dimensional echocardiography showed marked enlargement of left ventricle. Cardiomegaly was probably multifactorial (chronic hypertension, ischemic heart disease and acromegaly). To our knowledge, this is the first reported case of massive cardiomegaly behaving as an intraabdominal mass. This possibility must be considered when invasive intraabdominal diagnostic procedures are to be done, particularly in an acromegalic patient.

Abdomen↗