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PubMed1983

Correlation between increased serum and tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients.

A group of 14 uremic patients on intermittent hemodialysis was admitted to a cross-over double-blind trial in order to evaluate serum and muscle carnitine levels before and after 60 days of L-carnitine oral (2 g/day) treatment. The morphology of muscle fragments was studied by light and electron microscopy. Symptoms (asthenia, cramps) occurring during hemodialysis were also recorded. After L-carnitine treatment the blood and muscle levels of the metabolite increased simultaneously to reduced asthenia and cramps. Morphological examination of the muscle of 13 of 14 patients did not reveal any pre- or posttreatment pathological alterations. The presence of nemaline rods was morphologically diagnosed in only one case and was no longer observed at the second biopsy at 2 months of L-carnitine treatment.

Adult↗
PubMed2005

Phase II randomised trial comparing docetaxel given every 3 weeks with weekly schedule as second-line therapy in patients with advanced non-small-cell lung cancer (NSCLC).

BACKGROUND: Taxotere (docetaxel) at the dose of 75 mg/m(2) every 3 weeks is a standard therapy for pretreated non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the safety profile of two schedules of docetaxel administration (every 3 weeks versus weekly) in patients with pretreated NSCLC. PATIENTS AND METHODS: From February 2000 to February 2001, 125 patients with locally advanced or metastatic NSCLC were randomised after failure of a previous platinum-based regimen to receive either docetaxel 75 mg/m(2) administered every 3 weeks (Dq3w) or docetaxel 40 mg/m(2) given weekly for 6 weeks followed by 2 weeks of rest (Dqw). Safety evaluations focused on grade 3-4 neutropenia, febrile neutropenia, nausea-vomiting and asthenia. RESULTS: Patients' characteristics were well balanced between arms. The most common National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3-4 toxicity was neutropenia, which occurred in 48.4% of Dq3w patients versus 15.9% of Dqw patients (P=0.001). In addition, febrile neutropenia were observed in 6.5% of patients in Dq3w versus 0% in Dqw. Grade 3-4 asthenia was more frequent in Dqw. Other non-haematological toxicities were very rare. Regarding efficacy, there was a trend towards a better disease control rate in Dq3w: 32.2% versus 25.4% in Dqw. Median time to progression and survival were rather similar in both arms, respectively: 2.1 months (range 2-3.2) and 5.8 months (range 4.0-7.0) in Dq3w and 1.8 months (range 1.6-2.3) and 5.5 months (range 3.7-6.6) in Dqw. CONCLUSIONS: While both schedules had a favourable safety profile, a significant lower rate of severe neutropenia was observed in the weekly arm. Both regimens had similar efficacy. The weekly regimen could be considered as a good alternative for patients at risk of severe neutropenia.

Adult↗
PubMed2004

Dose escalation study on oxaliplatin and capecitabine (Xeloda) in patients with advanced solid tumors.

OBJECTIVES: Capecitabine (CAP) and oxaliplatin (OX) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of their combination in patients with refractory solid tumors. PATIENTS AND METHODS: Thirty-three pretreated patients with histologically confirmed inoperable neoplasms were enrolled. The patients' median age was 64 years, 21 were males, and 27 had a WHO performance status of 0-1. OX was administered on days 1 and 8, as a 3-hour intravenous infusion, at escalated doses ranging from 50 to 70 mg/m(2). CAP was administered orally for 14 consecutive days, at escalated doses ranging from 1,200 to 2,100 mg/m(2)/day. Treatment was repeated every 3 weeks. RESULTS: At the dose of 2,100 mg/m(2) (Xeloda) and 70 mg/m(2) (OX), all 3 enrolled patients presented DLT (grade 3 diarrhea, grade 3 asthenia and grade 3 neurotoxicity, respectively), and, thus, the recommended MTD for future phase II studies are 2,000 mg/m(2) for CAP and 70 mg/m(2 )for OX. A total of 145 treatment cycles were administered. Toxicity was very mild. Grade 2/3 neutropenia was observed in 4 (3%) treatment cycles. The main nonhematologic toxicities were grade 2/3 nausea/vomiting (7 cycles; 5%), grade 2/3 neurotoxicity (10 cycles; 7%), grade 2/3 asthenia (8 cycles; 5.5%) and grade 2/3 diarrhea (6 cycles; 4%). There was no treatment-related death. One (4%) complete remission, 2 (8%) partial remissions, and 9 (36%) cases of stable disease were observed among 25 evaluable patients. CONCLUSIONS: The results demonstrate that CAP and OX can be safely combined at clinically relevant doses and that this regimen merits further evaluation.

Aged↗
PubMed1997

Symptomatic improvement after AV nodal ablation and pacemaker implantation for refractory atrial fibrillation and atrial flutter.

Symptomatic Improvement was evaluated in 64 patients with drug-refractory atrial fibrillation or atrial flutter who underwent atrioventricular (AV) nodal ablation and permanent pacemaker implantation. The arrhythmias were chronic in 40 patients and paroxysmal in 24 patients. All were refractory to multiple drugs (3.7 +/- 1.5) and had severe symptoms: palpitations (58 patients), dyspnea (n=58), dizziness (n=38), asthenia (n=37), and chest pain (n=20). All underwent AV nodal ablation and single- (n=39) or dual-chamber (n=25) pacemaker implantation. During follow-up of 20.4 +/- 17.8 months, palpitations improved in 100% of 58 patients who had palpitations before the ablation, dyspnea improved in 75% of 58 patients, chest pain in 95% of 20 patients, asthenia in 75% of 37 patients, and dizziness in 93% of 38 patients. Moderate to significant improvement in these symptoms was reported in 83% of patients and mild improvement in 5%. Before ablation, 77% of patients were in New York Heart Association functional class III or IV. After ablation, 19% of patients were in the same functional classes (P < 0.05). Thus, AV nodal ablation and pacemaker implantation in patients with drug-refractory atrial fibrillation or flutter was associated with significant improvement in presenting symptoms and functional capacity. A randomized, controlled study is needed to compare this form of therapy with other therapeutic modalities.

Aged↗
PubMed2000

Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: a University of Chicago Phase II Consortium study.

PURPOSE: Flavopiridol is the first cyclin-dependent kinase (cdk) inhibitor to enter clinical trials. Serum levels of flavopiridol obtained during phase I studies were sufficient to inhibit in vitro cancer cell growth. Because responses were observed in kidney cancer patients in the phase I trials, we performed a phase II trial of flavopiridol in this patient population. PATIENTS AND METHODS: Thirty-five minimally pretreated patients were accrued using a standard two-step mechanism. Flavopiridol (50 mg/m(2)/d) was administered by continuous infusion for 72 hours every 2 weeks, and response was evaluated every 8 weeks. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, at completion of drug infusion, and on day 7 of the first therapy cycle, and cell cycle parameters after phytohemagglutinin and interleukin-2 stimulation were assessed. RESULTS: There were two objective responses (response rate = 6%, 95% confidence interval, 1% to 20%). The most common toxicities were asthenia, occurring in 83% of patients (grade 3 or 4 in 9%), and diarrhea, occurring in 77% of patients (grade 3 or 4 in 20%). Also, nine patients (26%) experienced grade 3 or 4 vascular thrombotic events, including one myocardial infarction, two transient neurologic ischemic attacks, four deep venous thrombosis, and two pulmonary emboli. Cell cycle studies did not reveal any effect of flavopiridol on stimulated PBMCs. CONCLUSION: Flavopiridol, at the dose and schedule administered in this trial, is ineffective in metastatic renal cancer. In addition to the diarrhea observed in phase I studies, we also observed a higher incidence of asthenia and serious vascular thrombotic events than expected.

Adult↗
PubMed1976

Serum dopamine beta-hydroxylase in cardiovascular diseases.

Dopamine-beta-hydroxylase (DBH), the enzyme responsible for the biosynthesis of norepinephrine from dopamine was assayed in the blood serum of 23 normal adults, 16 patients with congestive heart failure, 19 patients with asymptomatic ischemic heart disease, 4 patients with angina pectoris at rest, 15 patients with essential hypertension, 8 patients with essential hypotension, 5 patients with neurocirculatory asthenia, and 9 normal adults before and after the exercise test. The serum DBH activity varied within a wide range in the control population. The DBH activity increased about 16% after the exercise stress. A tendency to increase DBH activity was shown in the patients with congestive heart failure. There was no significant difference between asymptomatic ischemic heart disease, essential hypertension and normal controls. A lower value was observed in the patients of angina pectoris at rest, while a higher DBH activity was demonstrated in the patients with essential hypotension. There was no significant difference between the neurocirculatory asthenia group and the normal control group.

Adult↗
PubMedDate not supplied

Osteoporosis with lymphoid nodules and hematopoietic marrow hyperplasia.

OBJECTIVE: In 1983 Vigorita reported 3 cases of osteoporosis associated with intramedullary lymphoid nodules. We present 8 patients with osteoporosis and lymphoid nodules (LN) in whom we studied the clinical, biological and histological features and the course of the disease. METHODS: Three men (mean age 52 yrs., range 43-68 yrs.) and 5 women (mean age 60 yrs., 49-66 yrs.), 6 of them with osteoporosis with fracture and 2 with osteoporosis on bone densitometry (T score < -2.5 SD) were enrolled in this study. The following parameters were studied: immunobinding with IG determination, phosphorus and calcium levels, PTH, 25 and 1-25 OH D3, osteocalcin, urinary deoxypyridinoline, histomorphometry, tests for autoanti-bodies, HIV, HTLV, EBV and CMV serology. The results were compared with those of 20 patients with osteoporosis but without LN. Five patients underwent a second BMB a mean of 2 years after the first. RESULTS: Five patients had asthenia, 4 had joint pain and 3 had hyperlymphocytosis. Immunologic and virologic investigations were negative in all cases. Bone marrow was hypercellular (59.9 +/- 5.3 vs 40.1 +/- 13%, p: 0.001). At the second BMB, LN were absent but bone marrow was still hypercellular. In all cases, no cause of demineralization was found and osteoporosis progressed rapidly (an average of 3 vertebral compression fractures in three months, with increased resorption (ES 6.5 +/- 1.6 vs 3 +/- 1.2, p: 0.05) with decreased calcification rate (CR 0.62 +/- 0.07 vs 0.79 +/- 0.1, p: 0.04). CONCLUSION: Some interesting questions are raised by this study. Did an undiscovered viral infection cause the asthenia and joint pain via cytokines or PTHrp in our patients, and can activated lymphocytes perhaps modify bone remodeling?

Adult↗
PubMedDate not supplied

[Evaluation of the effect of tobacco on trandolapril tolerance].

The objective of this study was to evaluate the impact of smoking habits on safety of trandolapril assessed by interrogation and by visual analogue scales (VAS). A total of 3402 hypertensive smokers (> or = 1 cigarette/d for at least 6 months) and non-smokers (no smoking or ceased at least 6 months previously) received trandolapril 2 mg/d for 4 weeks. The safety profile of trandolapril was assessed by both interrogation and by VAS. The VAS completed by the patients at D0 and D28 explored the following symptoms: asthenia, nausea, cough, headaches and dizziness. A significant change in cough VAS was previously defined by an at least 19 mm change. VAS analysis was performed on 2840 patients (1296 smokers and 1544 non-smokers), mean age 59 +/- 12 years. Smokers and non-smokers were significantly different for age 56 +/- 12 years vs. 62 +/- 12 years, sex ratio 74 per cent males vs. 45 per cent, history of hypertension 4.5 +/- 6.1 years vs. 5.3 +/- 6.5 years and cough VAS score at D0 35 +/- 26 mm vs. 20 +/- 21 mm. In the total population, 214 adverse events were reported by 177 patients (5.2 per cent). The most frequent adverse events were a cough (2.1 per cent), bronchitis (0.6 per cent), headaches (0.5 per cent), rhinitis (0.4 per cent), nausea (0.4 per cent) and asthenia (0.3 per cent). Cough was reported by 23 smokers (1.5 per cent) and by 49 (2.6 per cent) non-smokers (p = 0.02). In the VAS population, 151 adverse events were reported by 130 patients, 47 smokers (3.6 per cent) and 83 non-smokers (5.4 per cent, p = 0.03). The difference between the two groups was mainly due to a cough: 15 smokers (1.2 per cent) reported a cough vs. 38 non-smokers (2.5 per cent, p = 0.01) and 77 smokers (5.9 per cent) presented a significant change of cough VAS score vs. 124 non-smokers (8.0 per cent, p = 0.03). In this large scale study, 1.9 per cent of patients treated with trandolapril exhibited a cough. Smokers were less likely to present a cough. Use of VAS confirmed this trend.

Adult↗
PubMedDate not supplied

Phase I study of docetaxel administered by bi-weekly infusion to patients with metastatic breast cancer.

BACKGROUND: To find a more convenient and tolerable schedule than the tri-weekly or weekly schedules, we conducted a dose escalation study of bi-weekly docetaxel. MATERIALS AND METHODS: Between March 1998 and June 1999, 16 patients entered this phase I study. The starting dose was 40 mg/m2, with planned dose escalation to 45, 50 and 55 mg/m2, in consecutive patient cohorts. Patients continued to receive the assigned treatment at the same dose level bi-weekly, provided that they did not develop progressive disease, refuse further treatment, or experience unacceptable toxicity. RESULTS: Grade 4 neutropenia lasting for more 4 days was seen at dose level 3 in all three patients. Only one patient who had previously received intensive chemotherapy required granulocyte colony stimulating factor (G-CSF) to prevent neutropenic fever and there were no actual episodes of neutropenic fever. Grade 3 asthenia and Grade 3 elevation of serum glutamic oxaloacetic transaminase were noted in only one patient treated at a dose of 40 mg/m2. Grade 3 skin toxicity and grade 2 elevation of serum glutamic oxaloacetic transaminase were seen in only one patient treated at a dose of 55 mg/m. Cumulative toxicity was not severe in all patients. Although grade 3 and/or grade 4 neutropenia were noted in eight patients (50%), all except one who received treatment at dose of 55 mg/m2 did not need G-CSF. Nail toxicity and peripheral edema seemed to be related to the number of treatment cycles. Severe fatigue and asthenia were never seen in all patients. CONCLUSION: 1) The maximum-tolerated dose of docetaxel when administered by this bi-weekly schedule was 55 mg/m2; 2) Docetaxel administered on a bi-weekly basis well tolerated.

Adult↗
PubMed2001

Pharmacologic management of nonpain symptoms in surgical patients.

Palliative care patients present with multiple symptoms other than pain and cachexia. Asthenia, delirium, dyspnea, and chronic nausea and constipation cause significant distress to patients and families and frequently coexist in the same patient. A careful assessment frequently identifies reversible causes. When none are identified or there is no improvement, symptomatic pharmacologic interventions are available. The success rate is variable, and it is very high for symptoms such as chronic nausea or constipation and less effective for symptoms such as asthenia and delirium. More research on the mechanism and treatment of these symptoms is needed.

Algorithms↗
PubMed2001

[Treatment of asthenic disorders with tanakan].

AIM: To evaluate efficacy and safety of tanakan in different asthenic disorders. MATERIAL AND METHODS: Tanakan in a dose 240 mg/day was used in 60 patients with various asthenic disorders arising in neurasthenia and late after craniocerebral trauma. The response was assessed by the scale of general clinical impression, side effects and by changes in psychic and somatic status. RESULTS: The response was achieved in 90% of the patients. 78% had significant improvement regardless nosological entity of asthenia. CONCLUSION: Tanakan is safe and effective in therapy of asthenic disorders. Moreover, with tanakan asthenia can be treated without polypragmasia.

Antioxidants↗
PubMed2002

[Correction of asthenovegetative disorders in the postoperative period in pulmonary tuberculosis patients].

UNLABELLED: 58 patients with asthenia were observed during postoperative period after surgery treatment of tuberculosis. All of the patients were divided into two groups: 34 patients taking anti tuberculosis drugs and Stimol, and 24 patients taking only anti tuberculosis drugs. Following method where used to appreciate states of the patients: scales of Symptoms Check List--90, acid-base and gas state of blood, EKG, ECHOKG, KIG, Contactles Spirometry. RESULTS: Treatment with using of Stimol leads to quicker regress of asthenia to improvement in both cardiovascular and respiratory systems and normalization of gas state of blood. Effect of this medicine can be connected with positive influence on cardiac and respiratory functions of the body due to normalization vegetative prevision and improvement of metabolism in cells of drain and cardiomyocyties.

Asthenia↗
PubMed1986

[Clinical problems in mitral valve prolapse: an electrocardiographic review].

Electrocardiographic signs of mitral valve prolapse are essentially non-specific. Diagnosis must be based on the other methods, but whenever the diagnosis was established, the electrocardiographic abnormalities may have a certain significance to predict the natural course and prognosis. The reported results and those of our series of 111 cases were compared in detail. Resting and exercise electrocardiography of our series revealed no definite tendency of ST-T changes, arrhythmias and other abnormalities in cases with prolapse except a few signs. When the abnormalities were present, they were not related to the severity of prolapse, but premature ventricular contractions were more frequently observed in severe cases. Atrial fibrillation was observed in higher frequency in cases with mitral regurgitation. The other abnormalities were not conclusive to verify previous studies. When compared to 19 cases with neurocirculatory asthenia comfirmed by clinical tests including angiography, the similarity of electrocardiographic abnormalities was observed in many aspects, but arrhythmias were much more common in cases with mitral valve prolapse. On the other hand, exercise test was positive more frequently in cases with neurocirculatory asthenia. No conclusion was established as to the sites of prolapse and electrocardiographic abnormalities.

Adolescent↗
PubMed1984

[The preoperative mental state].

In four studies psychological and psychophysiological correlations to anesthesiologically important factors were investigated. The most important preoperative emotions are anxiety, depression and asthenia. These emotions are part of the preoperative stress response. It was investigated which factors are correlated to these emotions and how these emotions correlate to physiological parameters, important in anesthesia. Sex, age, the quality of former experience of anesthesia and suffering of a chronic disease influence the degree of preoperative emotional stress. Cancer or the suspect of cancer increase preoperative anxiety. The preoperative psychological state correlates to blood pressure, heart rate and P-cortisol as well as to complications in anesthesia. There are two psychophysiological risk groups: Patients in a bad psychological state and patients in a good psychological state. Patients in the mean group have the best prognosis. Differences depending on the emotions anxiety depression and asthenia are described and discussed.

Age Factors↗
PubMed1993

[Asthenic disorders in persons infected with HIV at the initial stages of the disease].

Clinical psychopathological, follow-up and neuropsychological evaluation was made for 125 HIV-infected patients in stage 2B of the disease (general lymphadenopathy by V. I. Pokrovskiĭ's classification). It is shown that seropositive subjects had asthenic syndrome for the initial 6 months of the disease. According to the manifestations, asthenia was defined as psychogenic-reactive and organic. In the former variant the treatment involved psychotherapy and occasionally drugs, the latter was treated with chemotherapy and psychopharmacological modalities as the first-line and psychotherapy as adjuvant means. The authors expect that a differential approach to HIV-infection-related asthenia at the disease onset may contribute to better life quality and prognosis in AIDS patients.

AIDS-Related Complex↗
PubMedDate not supplied

[Hypothyroid myopathy in a young adult].

We describe here the case of a young man admitted to our department for asthenia and diffuse myalgia. Because of persistently increasing aminotransferase levels over the preceding 2 years, he had undergone a number of diagnostic procedures to evaluate liver function. On admission to our department, the patient suffered from asthenia, myalgia, notable hair loss and sinus bradycardia. Laboratory examinations confirmed severe primary hypothyroidism with high serum levels of aminotransferase, aldolase and creatine-phosphokinase attributable to thyroprivic myopathy. The thyroid deficit was caused by autoimmune atrophic thyroiditis. Treated with levothyroxine, the patient recovered fully from his illness, his normal metabolic state was restored, and his serum aminotransferase level returned to normal.

Adult↗
PubMed2001

Physostigmine for Alzheimer's disease.

BACKGROUND: The main pharmacological approach for the treatment of Alzheimer's disease (AD) has been based on the use of agents potentiating cholinergic transmission, particularly by inhibiting acetylcholinesterase (AChE), the enzyme that destroys acetylcholine after it has been secreted into the synaptic clefts. Physostigmine is an AChE inhibitor originally extracted from calabar beans. It is licensed in many countries as an agent for reversing the effect of drugs and poisons causing the anticholinergic syndrome. Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia. Investigation of this property has been limited by the very short half-life of physostigmine. Various forms of administering the drug have been tried to overcome this problem, most recently a controlled-release (CR) oral formulation, and a skin patch. It has been proposed as a potential drug for the symptomatic treatment of AD. OBJECTIVES: To determine whether there is evidence of beneficial effects for the use of physostigmine in Alzheimer's disease. To assess the incidence and severity of adverse effects. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched using the following terms: 'physostigmine', 'physostigmine salicylate', 'Synapton' and 'Antilirium' in accordance with the Cochrane Dementia and Cognitive Improvement Group's search strategy. The pharmaceutical company was contacted. SELECTION CRITERIA: All relevant unconfounded, double-blind, randomized, placebo-controlled trials in which physostigmine was administered for more than one day to patients with dementia of Alzheimer type. Trials in which the allocation to the treatment was not randomized, or in which the allocation to the treatment was not concealed were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers (JMC & JB), pooled where appropriate and possible, and the weighted or standardized mean differences or Peto odds ratios (95% CI) were estimated. Where possible, intention-to-treat analysis was used. MAIN RESULTS: Fifteen studies were included using four different methods of administration of physostigmine. Four studies, involving 29 people in total, used intravenous infusion; seven, involving 131 people, used a conventional oral form; four, involving 1456 participants, used a controlled-release oral form, and one study of 181 people used a verum skin patch. There are no usable results from the intravenous infusion trials, and the few results from the conventional oral form showed no benefit of physostigmine compared with placebo. The results from two of the four studies of the controlled-release physostigmine apply only to a group of patients identified as responders in a pre-randomization titration period. The best dose physostigmine (mean 25mg/day) was associated with a 1.75 point improvement on ADAS-Cog score (mean difference -1.75, 95% confidence interval -2.90, -0.60 on an intention-to-treat basis) and a 0.26 point improvement on the CGIC score (treated as a continuous scale) (mean difference -0.26, 95% confidence interval 0.06, 0.46 on an intention-to-treat basis) compared with placebo at 6 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial (22/183 vs 2/183)(OR 5.92, 95% confidence limits 2.59, 13.54) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, flatulence or sweating compared with placebo at 6 weeks. The best dose physostigmine (mean 27mg/day) was associated with a 2.0 point improvement on ADAS-Cog score (mean difference -2.02, 95% confidence interval -3.59, -0.45 on an intention to treat basis) compared with placebo at 12 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial due to adverse events (13/83 vs 5/93)(OR 3.05, 95% confidence limits 1.15, 8.07) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, tremor, asthenia or sweating compared with placebo at 12 weeks. When no attempt was made to identify responders and all relevant patients with Alzheimer's disease were randomized, fixed dose physostigmine (mean 33 mg/day) was associated with a statistically significantly higher number withdrawing (234/358 vs 31/117)(OR 4.82, 95% confidence limits 3.17, 7.33), withdrawing due to adverse events (196/358 vs 10/117) (OR 6.54, 95%confidence limits 4.29, 9.95) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, dyspepsia, sweating, asthenia, dyspnoea or abnormal dreaming compared with placebo at 24 weeks. The results from the study of the verum patch physostigmine show that the double dose (delivering mean dose 12mg/day) was associated with statistically significantly higher numbers suffering at least one adverse event of vomiting, nausea or abdominal cramps compared with placebo at 24 weeks, but placebo was associated with statistically significantly greater numbers of gastrointestinal complaints at 24 weeks compared with single-dose physostigmine. REVIEWERS' CONCLUSIONS: The evidence of effectiveness of physostigmine for the symptomatic treatment of Alzheimer's disease is limited. Even in a controlled release formulation designed to overcome the short half-life, physostigmine showed no convincing benefit and adverse effects remained common leading to a high rate of withdrawal.

Alzheimer Disease↗
PubMed2004

Reducing the time interval between cycles using standard doses of docetaxel and lenogastrim support: a feasibility study.

BACKGROUND: As a single agent, 100 mg/m(2) of docetaxel every 3 weeks remains the standard schedule in the first-line treatment for metastatic disease. At this dose level, the major limiting toxicity is neutropenia. The current study was conducted to assess the feasibility of reducing time intervals between cycles while delivering standard doses of docetaxel with granulocyte-colony-stimulating factor (G-CSF; lenograstim). METHODS: In the first part of the study, 24 patients were randomized to receive 1 of 4 schedules: 100 mg/m(2) of docetaxel every 21 days without lenograstim; 100 mg/m(2) of docetaxel every 18 days with lenograstim; 100 mg/m(2) of docetaxel every 14 days with lenograstim; or 100 mg/m(2) of docetaxel every 10 days with lenograstim. In the second part of the study, 15 additional patients were included to confirm the feasibility of the recommended interval between cycles. RESULTS: Of the 39 patients treated, 14 patients (36%) withdrew from therapy because of Grade 3 (according to standard World Health Organization criteria) nonhematologic limiting toxicities. Only 3 patients were treated in the 10-day interval arm and were withdrawn because of toxicity--1 patient had Grade 3 asthenia after the second cycle and 2 patients had Grade 3 dermatitis after 4 cycles. Of the 24 patients treated in the 14-day intervals, Grade 3 limiting toxicities occurred in 8 patients (33%), including dermatitis in 3 patients; diarrhea, myalgia/arthralgia, or asthenia in 4 patients; and ungual toxicity in 1 patient. CONCLUSIONS: Introduction of G-CSF (lenograstim) as primary prophylaxis allowed the administration of docetaxel every 14 days with manageable toxicities. Further studies are now required to assess the impact in terms of response rates and survival in patients with cancer.

Adult↗