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[Development of a scale for assessing lack of motivation in elderly persons].

OBJECTIVE: Apathy is made of depression and of loss of motivation. For patients with senile dementia of Alzheimer-type, the MMS score is inversely correlated with apathy and depression. The aim of this study is to build a scale aimed at loss of motivation and validated for elderly people. METHODS: The study was performed on 44 non-demented elderly people, 54 outpatients with dementia, mainly Alzheimer's type. After agreement of the patients and the family, patients were assessed using different scales: Cornell's for depression, Marin's for apathy, MMS for cognitive disorders. At the same time, we tested with caregivers a 21 items indirect scale listing various disorders related to loss of motivation, scored from 1 to 4: very often, often, sometimes, never. Patients were retested by 7 different caregivers, and different investigators, immediately and a month later to evaluate reproducibility, temporal stability using Cohen's Kappa and Spearman coefficients. The demotivation scale was then correlated with the other scales and Cronbach's alpha coefficient was studied. RESULTS: The 44 non-demented people were 80.25 years old +/- 7.75. 54 demented patients were included: 15 men and 39 women. The mean age was 81.47 years +/- 8.03. As Cohen's Kappa and Spearman coefficients were not sufficient for 6 items, the scale was reduced to 15 items (Presented). The depression scale is strongly and significantly correlated with the Marin's apathy scale. Internal coherence is particularly significant: Cronbach's alpha coefficient = 0.91. For the 54 patients with dementia, the depression score worsens significantly as cognitive disorders worsen. In these patients Marin's scale shows a progression of apathy with the impairment observed in MMS, but the MMS is not correlated with the score at the demotivation scale. So this latter scale seems to measure something close but independent from apathy. DISCUSSION: The loss of motivation is a frequent behavioral disorder in old patients. Loss of motivation can be present in any chronic disease with asthenia. This disorder is frequent in depression, in dementia and even in endocrine disease, for instance hyperthyroidism. It triggers a loss of commitment of old people and paves the way for the loss of autonomy. Apathy is a loss of motivation associated with an affective blunting. Demotivation is congruent with the actual presence of apathy in patients as measured using Marin's scale that has been used as a standard in this study. This paper presents a methodology for an evaluation scale aimed at the loss of motivation in old people. A psychologist and seven different caregivers working in a day care hospital on 98 patients performed an indirect assessment. An estimation of specificity, sensibility, reproducibility and homogeneity was tested with appropriate techniques. The results obtained with this scale answer the preliminary methodological queries, allowing us to trigger further researches for a final validation. According to our results, demotivation does not increase with age neither in demented nor in non-demented patients. Conversely, the aggravation of cognitive disorders in dementia is associated with increasing demotivation and depression. The loss of motivation participates to the learnt and acquired helplessness. Its care is necessarily global, using pharmacological, psychological and sociotherapeutic treatment. CONCLUSION: EAD scale appears a reliable tool to assess loss of motivation in old and very old patients.

Aged↗

[Massive pericardial effusion and cardiac tamponade as the presentation form of hypothyroidism].

We report a 43 years old female, admitted due to fatigability, asthenia and diffuse abdominal pain. On admission, obesity, slowness of thinking, bradycardia, distention of jugular veins and ascites were observed on physical examination. Laboratory showed undetectable thyroid hormone levels, a chest X ray showed bilateral pleural effusion and an enlarged heart. An echocardiography showed a massive pericardial effusion with collapse of the right atrium and dilatation of both caval veins. A pericardial tap was performed, draining 350 ml. Thyroid hormone substitution was started and after 12 months of follow up, the heart size decreased and a control echocardiogram showed a minimal pericardial effusion.

Adult↗

[Lead poisoning in adults. Experience of the Poison Control Center of Marseille from 1993 to 2000].

OBJECTIVE: Report the experience of the Marseille's anti-poison center with lead poisoning adults. PATIENTS AND METHODS: Between 1993 and 2000, 45 adults patients consulted the poison Centre of Marseille for a history of lead exposure (9 women, 36 men, average age 44 YO, between 22 an 76 YO). The lead sources were mostly occupational (welding, heavy metal industries...), but some were environmental (shooting as a hobby, hunting,...). RESULTS: Ninety-one percent of the patients presented with a clinical feature of possible lead intoxication (asthenia, abdominal pain, anaemia, seizures,...). For 22 patients, calcitetracemate provocation test was negative. 6 patients with a positive test refused to be treated. 16 patients with a positive test were treated with chelation therapy (average lead blood level 566 micrograms/l--mini 320 micrograms/l, maxi 943 micrograms/l--and average lead urine elimination 3,011 micrograms/24 H--mini 789 micrograms/24 H, maxi 7,229 micrograms/24 H. 58 cures were done (1 to 12 cures for each patient). The average quantities of lead eliminated in the urine during the chelation therapy was 30,912 micrograms +/- 29,059 micrograms by case. For 12 patients who stopped the lead exposure after the diagnosis of lead poisoning, the chelaion therapy permitted to decrease the lead blood level of 69%. For 4 patients still exposed during the treatment, the lead blood level decrease of 7% only. For the 16 treated patiEnts, a clinical improvement was noted, and no adverse effects of chelation therapy was observed during the 58 cures.

Adult↗

[Experimental study on effect of bushen yijing recipe in delaying senility of bone and brain of aged male rats].

OBJECTIVE: To evaluate the effect of Bushen Yijing recipe (BSYJR) in delaying senility of bone and brain of aged male rats and infer its mechanism in delaying systemic senility. METHODS: Forty male SD rats, 24 months old were randomly divided into 4 groups, the baseline control group, the aged control group (30 months old), the BSYJR high dose group and the BSYJR low dose group. The latter two groups received BSYJR treatment from 24 months old to 30 months old. Bone indexes (bone density of the proximal, middle and distal segments of left femur and break bending load of right femur) and brain indexes (binding capacity of M receptor and cholinesterase activity of brain) were measured after responding treatment. RESULTS: In bone, BSYJR could not only increase the bone mineral density in various segments of femur, but also raise the bending break load of femur dose-effect dependently. In brain, BSYJR could both up-regulate the binding capacity of M receptor and inhibit the activity of cholinesterase. CONCLUSION: BSYJR could delay the senility of bone and brain in male rats, inferring that it might regulate integrally the abnormality of aging in Kidney Asthenia and Essence Deficiency through mediation of nerve-endocrine-immunity network.

Aging↗

[Therapeutic indications for managing symptoms: fatigue].

Fatigue is a common complaint in patients affected by multiple sclerosis. Its mechanisms are poorly understood and are likely diverse. The term "fatigue" has been used for asthenia at rest but also for fatigability during exercise. Amantadine is the only drug that has a proven therapeutic benefit in randomized, double blind, controlled trials. Inhibitors of serotonin re-uptake are used pragmatically because of the relationship between fatigue and depression. Aminopyridins may improve fatigability, mainly at the level of lower limbs.

Amantadine↗

[An exceptional case of hypersensitivity to actinomycin D. Case report and review of the literature].

We report the first case, to our knowledge, of an allergic attack following the administration of Act-D in a 9 year old boy, affected by orbit embrional rabdomyosarcoma. The boy was given most operative therapy according to RMS 96 protocol, IRS group IIb, with Actinomicin D (Act-D), Vincristine and Ifosfamide and RT. Immediately after the beginning of chemotherapy the boy presented with an asthma-like attack (dyspnoea and asthenia), supposed to be a side effect of Ifosfamide administration regressed by intravenous bolus of hydrocortisone and chlorphenamine. In the second chemotherapy cycle concurrent with RT, the Act-D preceded the administration of ifosfamide. Subsequently to the administration of Act-D and RT, without premedication, the boy presented with a face erythema and asthma like attach. Post operative chemotherapy was achieved with no further allergic side effect using premedication with hydrocortisone and chlorphenamine. The boy is now 13 years old, alive and disease free at a three years follow-up.

Antibiotics, Antineoplastic↗

[Unusual case of malaria in Italy].

There is a significant increase in cases of malaria in Italy. The incidence among Italian citizens has remained quite stable since 1990, while the number of cases among foreigners residing in Italy has continued to increase. The clinical manifestations of plasmodium infection can be less evident in these people: they often have only mild complaints for weeks or months. The case of a Senegalese woman with Plasmodium malariae infection is presented. She had been in Italy for 13 months and was 4-month pregnant. Her only symptoms were asthenia and microcytic anemia; she was afebrile. Her anemia was initially believed to be due to iron deficiency: she was treated with iron and folic acid. The anemia worsened, and resolved only after antimalarial therapy with chloroquine.

Adult↗

[Reversible myocardial ischemia in hypothyroidism: Case report].

A silent, reversible myocardial ischemia with normal coronary angiography and reversible with thyroid hormone substitution, has been recently described in hypothyroid patients. We report a 49 years old male with an abnormal exercise electrocardiogram detected in a preventive medical examination. He had laboratory evidence of hypothyroidism and a history of two years of asthenia and progressive coarsening of the voice. The Thallium myocardial perfusion study, showed an alteration of coronary flow during exercise in the septum and lower wall of the left ventricle. Thyroid hormone substitution was started and three months later, a coronary angiography was normal. After six months a repeated Thallium perfusion study and exercise electrocardiogram were informed as normal.

Coronary Angiography↗

Terazosin for treating symptomatic benign prostatic obstruction: a systematic review of efficacy and adverse effects.

OBJECTIVE: To systematically review and evaluate the effectiveness and adverse effects of the alpha-antagonist, terazosin, for treating urinary symptoms associated with benign prostatic obstruction (BPO). METHODS: Studies were sought and included in the review if they were randomized trials of at least 1 month duration, involved men with symptomatic BPO and compared terazosin with placebo or active controls. The study, patient characteristics and outcome data were extracted in duplicate onto standardized forms using a prospectively developed protocol. RESULTS: Seventeen studies involving 5151 men met the inclusion criteria, i.e. placebo-controlled (10), alpha-blockers (seven), finasteride alone or combined with terazosin and placebo (one), and microwave therapy (one). The study duration was 4-52 weeks; the mean age of the men was 65 years and 82% were white. Baseline urological symptom scale scores and flow rates showed that men had moderate BPO. Efficacy outcomes were rarely reported in a way that allowed for data pooling, but indicated that terazosin improved symptom scores and flow rates more than did placebo or finasteride, and similarly to other alpha-antagonists. The pooled mean percentage improvement for the Boyarsky symptom score was 37% for terazosin and 15% for placebo (four studies). The mean percentage improvement for the American Urological Association symptom score was 38%, compared with 17% and 20% for placebo and finasteride, respectively (two studies). The pooled mean improvement in the International Prostate Symptom Score of 40% was similar to that with tamsulosin (43%). Peak urinary flow rates improved more with terazosin (22%) than with placebo (11%) and finasteride (15%), but did not differ significantly from the other alpha-antagonists. The percentage of men discontinuing terazosin was comparable with those receiving placebo and finasteride, but greater than with other alpha-antagonists. Adverse effects were greater than with placebo and included dizziness, asthenia, headache and postural hypotension. CONCLUSIONS: The available evidence indicates that terazosin improves the symptoms and flow rates associated with BPO; it was more effective than placebo or finasteride and similar to other alpha-antagonists. Adverse effects were generally mild but more frequent than with other alpha-antagonists and associated with a two- to four-fold increase in treatment discontinuation.

Adrenergic alpha-Antagonists↗

[Misuse and or overdose of BCG vaccine: evaluation over a 4-year period].

The inappropriate use of BCG vaccine could be followed by adverse events (AE). In order to know their frequency and type, we evaluated the spontaneous reports of misuses (MS) and overdosages (OV) over a 4-year period. One hundred and twenty-six notifications were collected; 109 concerned MS, 13 OV, and 4 concerned both MS and OV. We recorded a high number (97) of MS related to the injection of a BCG vaccine instead of a tuberculin test (TT). Among the 126 initial notifications, 122 cases of AE were reported, 107 after an MS, 11 after an OV and 4 after both MS and OV. The most common AE were related to injection-site reactions which were in fact expected reactions when BCG is used under correct conditions. In half of the cases systemic signs were associated. The most common were asthenia, fever and lymphadenopathy. Seven cases related to MS were considered as serious according to the ICH definition. Six of them recovered, for one the outcome was unknown. It appeared that perhaps the presentation of the products BCG vaccine and TT could play a role in contributing to this inappropriate use. Both presentations contain 10 doses but there are significant differences in colours used and in specific instructions. Despite the fact that the AE reported after an MS and/or an OV represented the one-third of the total notifications recorded with the BCG vaccine over the 4-year period under review, they have to be considered in light of the 170 million doses distributed in 150 countries. We have to consider the possibility of under reporting because of the delicacy of incorrect administration and differences in pharmacovigilance structures worldwide. Even if the number of AE is low, MS and OV should be reported and documented for good pharmacovigilance surveillance.

Adjuvants, Immunologic↗

Safety and efficacy of the multidrug resistance inhibitor Incel (biricodar; VX-710) in combination with paclitaxel for advanced breast cancer refractory to paclitaxel.

PURPOSE: VX-710 (biricodar, Incel) restores drug sensitivity to P-glycoprotein (MDR1) and multidrug resistance-associated protein (MRP1)-expressing cells. This Phase II study evaluated the safety/tolerability, pharmacokinetics, and efficacy of VX-710 plus paclitaxel in women with locally advanced or metastatic breast cancer who were refractory to prior paclitaxel therapy. EXPERIMENTAL DESIGN: Eligible patients had paclitaxel-refractory disease defined as progressive disease after a minimum of two cycles of paclitaxel (weekly or 3-week schedule) or relapsed/progressive disease within 6 months of prior paclitaxel therapy. Patients received 80 mg/m(2) paclitaxel over 3 h starting 4 h after initiation of a 24-h continuous i.v. infusion of 120 mg/m(2)/h VX-710. Cycles were repeated every 3 weeks. RESULTS: Thirty-seven patients received study treatment and 35 were evaluable for response. VX-710 + paclitaxel therapy was generally well tolerated. Myelosuppression was the principal toxicity, with a median nadir ANC cycle 1 of 0.76 x 10(9) cells/liter and a 40% overall incidence of Grade 4 neutropenia. Nonhematological side effects (asthenia, paresthesia, headache, myalgia, nausea, and diarrhea) were generally mild to moderate and reversible. Paclitaxel AUC (16.8 +/- 5.0 microg x h/ml) and clearance (5.1 +/- 1.3 liters/h/m(2)) during the first treatment cycle were comparable with standard 175 mg/m(2) paclitaxel administered in a 3-h schedule. Four patients achieved partial responses (three of the four had progressive disease on prior paclitaxel) with a mean response duration of 5.5 months. CONCLUSIONS: The 11.4% (4 of 35) objective response rate observed in this study suggests that VX-710 can resensitize a subgroup of paclitaxel-refractory patients to paclitaxel. The safety and pharmacokinetics of the VX-710/pacitaxel regimen support further evaluation in breast cancer patients with initial paclitaxel therapy to prevent emergence of the MDR phenotype in recurrent disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Phase I study of N(1),N(11)-diethylnorspermine in patients with non-small cell lung cancer.

PURPOSE: Polyamines are essential for tumor growth; consequently, agents that interfere with their metabolisms have been developed as antineoplastic agents. Diethylnorspermine (DENSPM) is one such agent. A focused Phase I clinical trial in patients with advanced non-small cell lung cancer was undertaken. EXPERIMENTAL DESIGN: Twenty-nine patients were treated with DENSPM using a dosing schedule of once daily for 5 days. Doses ranged from 25 mg/m(2)/day to 231 mg/m(2)/day. RESULTS: The dose-limiting toxicity was determined to be gastrointestinal including asthenia, abdominal cramps, diarrhea, and nausea. The maximal tolerated dose was 185 mg/m(2)/day for 5 days. At drug dosages for which it was possible to estimate, serum half-life ranged from 0.5 to 3.7 h without apparent dose dependence. Maximal serum concentrations increased with dosage. However, the increase was greater than the proportional increase of the administered dose. There were no objective disease responses observed during the Phase I trial. CONCLUSIONS: The results of the Phase I clinical trial suggest that DENSPM can safely be administered to patients with minimal toxicity. Furthermore, the observed dose-limiting toxicity is unique to DENSPM, thus underscoring the potential for DENSPM to be a suitable agent for chemotherapy in combination with agents possessing different spectrums of toxicities.

Adult↗

[Color-physiopuncture corrections of autonomic disorders].

Investigations have shown that electromagnetic waves of color band used for physiopuncture correction of functional-dynamic condition of channel-meridional system of the body in young patients with vegetovascular asthenia of a hypertensive type lead to a regress of the clinical symptoms, normalization of arterial pressure, correction of cerebral hemodynamic disorders, recovery of normal bioelectric activity of the brain.

Autonomic Nervous System Diseases↗

[Obsessive-phobic disorder typology in schizophrenia].

The study aims at clinical characteristics of obsessive-phobic disorders (OPD) in schizophrenia with regard to their modification in main disease development and interaction with basic schizophrenia symptoms (positive and negative). Eighteen patients, mean age 28.2 years, were examined. An affinity degree of schizophrenia to OPD was found to be associated with endogenous progressive process. In slowly progressive schizophrenia, an affinity is selective, concerning to one of the obsessive phobic syndrome component (phobic component proper or avoidance behavior) and realizing in either positive, or negative manifestation of schizophrenia. Two obsessive-phobic syndrome types were determined: OPD of the 1st type--panic and generalized anxiety disorder (52 patients) are modified because of overlapping by chronic endogenous anxiety, obsessive-phobic symptoms being not represented in structure of negative changes (asthenia defect); in OPD of the 2nd type (agora and social phobias, 80 patients) an overlapping of psychopathological symptoms related to avoidance behavior and negative changes (psychopathic-like defect "verschroben" type) was found. Phobic syndrome component does not tend to psychopathological transformation and undergoes reverse changes. In typical cases of progressive schizophrenia has no affinity. But exclusion is--the OPD of the 3rd type (obsessive-compulsive disorders with a fear of external threat and massive defense rituals, 49 patients). In this case, total affinity to schizophrenia is realized in overlapping of both obsessive syndrome components with positive and negative manifestation of schizophrenia.

Adult↗

Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale.

BACKGROUND: A prospective, randomized Phase III trial was performed to determine whether, compared with gemcitabine (GEM) alone, the addition of cisplatin (CDDP) to GEM was able to improve the time to disease progression and the clinical benefit rate in patients with advanced pancreatic adenocarcinoma. The objective response rate, overall survival rate, and toxicity patterns of patients in the two treatment arms were evaluated as secondary end points. METHODS: Patients with measurable, locally advanced and/or metastatic pancreatic adenocarcinoma were randomized to receive GEM (Arm A) or a combination of GEM and CDDP (Arm B). In Arm A, a dose of 1000 mg/m(2) GEM per week was administered for 7 consecutive weeks, and, after a 2-week rest, treatment was resumed on Days 1, 8, and 15 of a 28-day cycle for 2 cycles. In Arm B, CDDP was given at a dose of 25 mg/m(2) per week 1 hour before GEM at the same dose that was used in Arm A. On Day 22, only GEM was administered. Patients were restaged after the first 7 weeks of therapy and then again after the other 2 cycles. RESULTS: A total of 107 patients entered the trial: Fifty-four patients were randomized to Arm A, and 53 patients were randomized to Arm B. The median time to disease progression was 8 weeks in Arm A and 20 weeks in Arm B; this difference was statistically significant (P = 0.048). In Arm A, one complete response and four partial responses were recorded on the basis of an intent-to-treat analysis, with an overall response rate of 9.2% (95% confidence interval [95%CI], 3-20%). In Arm B, there were no complete responses, whereas 14 partial responses were achieved, with an overall response rate of 26.4% (95%CI, 15-40%). This difference in the overall response rates was statistically significant (P = 0.02). The tumor growth control rate (i.e., total number of patients who achieved complete responses, partial responses, and stable disease) was 42.6% (95%CI, 29-57%) in Arm A and 56.6% (95%CI, 42-70%) in Arm B. A clinical benefit was observed in 21 of 43 patients (49%) in Arm A and in 20 of 38 patients (52.6%) in Arm B without any significant difference. The median overall survival was 20 weeks for patients in Arm A and 30 weeks for patients in Arm B (P = 0.43). Toxicity was mild in both treatment arms, with no significant differences between the two groups except for the statistically higher incidence of Grade 1-2 asthenia in Arm B (P = 0.046). CONCLUSIONS: The addition of CDDP to GEM significantly improved the median time to disease progression and the overall response rate compared with GEM alone. The clinical benefit rate was similar in both arms, whereas the median overall survival rate was more favorable for Arm B, although the difference did not attain statistical significance. The authors conclude that the combination of CDDP and GEM currently may be considered as an optimal treatment for patients with locally advanced and/or metastatic adenocarcinoma of the pancreas.

Adenocarcinoma↗

Retinoids, cisplatin and interferon-alpha in recurrent or metastatic cervical squamous cell carcinoma: clinical results of 2 phase II trials.

BACKGROUND: There is no standard treatment for inoperable recurrent or metastatic cancer of the uterine cervix. Retinoids and interferon, in combination with cytotoxic compounds, have been shown to be active in squamous cell carcinoma (SCC). This phase II trial sought to estimate the response rate and the tolerance to a 3-month treatment combining cisplatin, interferon-alpha (IFN-alpha) and all-trans-retinoic (tRA) or 13 cis retinoic acid (13Cis), in women with recurrent or metastatic cervical SCC. PATIENTS AND METHODS: Between November 1994 and October 1996, 33 patients, who had previously received aggressive treatment, and with metastatic and/or bulky disease were enrolled: 22 received tRA(40 mg/m(2)/day), 11 received 13Cis (1 mg/kg/day) in combination with IFN-alpha (6.106 UI/day SC) for 84 days plus cisplatin (40 mg/m(2)IV, days 1, 28 and 56). RESULTS: All patients were evaluable for response and/or toxicity. Toxicities were easily manageable and were never life-threatening, with major grade 3/4 vomiting (54%) and asthenia (54%). Seventeen patients (52%) stopped or reduced treatment because of toxicity or progression. Six objective responses (18%) were observed. No complete response was recorded. Median response duration was 4 months. Time to progression was 9 months [range 3.3 to 20.9] for responders and 7 months [range 1.7 to 32] for all patients. CONCLUSIONS: Regarding toxicity, this regimen should no longer be recommended in previously treated, advanced uterine SCC. However, the consistent response rate reported here may warrant further investigations in an early setting. Retinoid-based treatment with cytokines remains a promising field of research.

Antineoplastic Combined Chemotherapy Protocols↗

[A 74-year-old woman with macrocytic anemia].

A seventy-four years old woman is assessed for asthenia, fatigue, non ulcerous dyspepsia with macrocytic anemia. The patient's medical history taking in Binswanger disease--diagnosed 5 aa before-, epilepsy-2 aa before- and a previous episode of TVP of the left leg, suggested the hypothesis that a B12 deficiency, by a chronic gastritis, would involve an increase of homocysteine cause of the clinical manifestations of megaloblastic anemia, Binswanger disease, tardive epilepsy and previous TVP. The fisic and blood and instrumental exams confirmed the clinical diagnosis. The patient is having vitamin B12.

Aged↗

[Subjective blockage in Parkinson's disease].

UNLABELLED: Akinetic symptoms or off-period motor signs in patients with Parkinson's disease and motor fluctuations can be associated with subjective symptoms. A systematic interview was conducted in a series of 24 patients. Sixteen out of 24 (67 p. cent) experienced these subjective symptoms as on-off non motor symptoms that were classified in three groups: energy lost consistent with a severe asthenia, perceptive and cognitive alterations, and emotional troubles such as panic and depression. These phenomenons could be combined in some patients and were sometimes asynchron to akinesia. In some patients (six cases reported), they occurred without any akinesia but could totally inhibit patients daily activities, and so could be described as subjective off-period . Frequently, the patients did not distinguish them from motor disability. Their persistence, after subthalamic nucleus stimulation or intrastriatal transplant, could interfere with functional results, even though akinetic symptoms had disappeared. CONCLUSION: subjective phenomenons during off-periods are frequent. Their frequency is underestimated due to a non-targeted examination. Subjective off-periods are symptoms of Parkinson's disease, partly independent from off motor symptoms, and important to consider in evaluation of therapeutics, especially surgery.

Aged↗