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PubMed1993

Adverse effects of antipsychotic drugs.

Since the introduction of chlorpromazine in the 1950s, neuroleptic medications have been the mainstay of treatment of schizophrenia and other psychotic disorders. These medications do not always lead to complete remission of symptoms but they have allowed many patients to lead more productive and satisfying lives away from the restrictions of chronic hospitalisation. However, neuroleptics are associated with a number of adverse effects that can compromise their effectiveness. Extrapyramidal adverse effects include acute dystonic reactions, neuroleptic-induced Parkinsonism and akathisia. They can often be treated with neuroleptic dose reduction, addition of anticholinergic or beta-blocking agents, or medication change. Later-onset movement disorders such as tardive dyskinesia or dystonia require careful evaluation and may be treated with dose reduction or change of neuroleptic to an atypical agent. Potentially fatal reactions such as agranulocytosis and neuroleptic malignant syndrome can rarely occur and often require significant medical intervention. Clozapine offers some advantages over 'typical' neuroleptics but has a unique adverse effect profile which includes agranulocytosis.

Akathisia, Drug-Induced↗
PubMed1985

Beneficial effects from systematic dosage reduction of the diuretic, chlorthalidone: a randomized study within a clinical trial.

The purpose of this study was to determine the effects on blood pressure and selected biochemical measures of reducing the dosage of chlorthalidone from 100 mg to 50 mg. Within the larger study (Multiple Risk Factor Intervention Trial), 140 Special Intervention hypertensive men, taking 100 mg of chlorthalidone daily, were randomly assigned to either a continuation of 100 mg or a dosage reduction to 50 mg daily. Men were followed monthly for 4 months. Measures were made of blood pressure, serum potassium, serum uric acid, serum glucose, serum cholesterol, and triglycerides. Blood pressure change from baseline to 4 months revealed a significantly higher diastolic blood pressure in the group continued on the 100 mg dose compared to the dose reduction group. However, analysis of covariance, which took into account baseline differences in blood pressure, resulted in a nonsignificant difference in follow-up blood pressure (systolic and diastolic) between groups. Serum potassium increased significantly in the dose reduction group, especially in those participants taking supplemental potassium chloride. The results of this study demonstrate that a reduced dose of 50 mg chlorthalidone over the 4-month period was as effective as the 100 mg dose in long-term, well-controlled hypertensive men. Careful study of other antihypertensive agents is warranted to determine the drug dose that is maximally effective for blood pressure lowering and that also minimized toxic and adverse effects.

Blood Glucose↗
PubMed1996

Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma.

PURPOSE: To determine the efficacy and toxicity of topotecan administered as a 5-day intravenous infusion in patients with advanced ovarian cancer refractory to cisplatin-based chemotherapy. PATIENTS AND METHODS: Thirty patients with advanced epithelial ovarian cancer refractory to cisplatin-based chemotherapy received intravenous infusions of topotecan 1.5 mg/m2 delivered over 30 minutes each day for 5 days. A course was repeated every 21 days. The patient eligibility requirements included age > or = 18 years, Zubrod score < or = 2, measurable disease, adequate hepatic and renal function, neutrophil count > or = 1,500/microL, platelet count > or = 100,000/microL, and anticipated survival > or = 3 months. RESULTS: Twenty eight patients were assessable for response and toxicity. All patients were assessable for survival. The major toxicity from administration of topotecan at this dose schedule was myelosuppression; 21 patients required dose reductions. Four patients had neutropenic fever that required hospitalization, and seven patients required platelet transfusions. Maculopapular pruritic exanthema occurred in 20% of patients; gastrointestinal side effects were mild. No deaths were reported on the study. At dose levels of 1.5, 1.25, and 1.0 mg/m2, 61%, 31%, and 25% of patients, respectively, required dose reductions. Of 28 assessable patients, four (14%; 95% confidence interval [CI], 4% to 34%) achieved a partial response (PR) at a median of 1.4 months and lasting 8.9 months, and 17 had stable disease (SD). The overall median survival time was 10.0 months (95% CI, 8.1 to 13.5). CONCLUSION: Topotecan shows modest clinical activity against cisplatin-refractory ovarian cancer, although the dose-intensity is compromised by the depth of the granulocyte nadir and the duration of granulocytopenia. Further studies of topotecan may necessitate a reevaluation of optimal dose schedule, with the possible incorporation of multilineage cytokines, and its activity in taxane-resistant tumors.

Adult↗
PubMed1999

The incidence of akathisia in bipolar affective disorder treated with neuroleptics--a preliminary report.

BACKGROUND: Akathisia is a common side effect of neuroleptic therapy. Prevalence and incidence studies of akathisia have been predominantly undertaken in patients with schizophrenia and schizoaffective disorder. Investigations of akathisia in neuroleptic treated patients suffering from bipolar disorder are lacking. METHOD: In the present study, 23 patients with bipolar affective disorder who were treated with neuroleptics were assessed for akathisia and parkinsonism, using the Barnes Akathisia Rating Scale and DSM-IV criteria, respectively. RESULTS: 15 patients (65.2%) developed akathisia. Eighteen patients (78.3%) had parkinsonism, including all of the akathisia-group. In six patients (40%) of the akathisia-group the onset of akathisia was after neuroleptic dose reduction or after additional administration of mood stabilizers. CONCLUSIONS: Neuroleptic-induced side effects may occur frequently in patients with bipolar affective disorder and should therefore be monitored thoroughly. Demasking effects due to diminishing parkinsonian symptoms may contribute to akathisia-onset after neuroleptic dose reduction. Early application of alternative treatment regimens, e.g. monotherapy with mood stabilizers in combination with benzodiazepines should be considered. FUTURE DIRECTIONS: The preliminary findings require further investigation regarding dose dependency, incidence of akathisia in untreated patients with bipolar affective disorder, akathisia in patients with depressed episodes on SSRI, and possible differences between various mood stabilizers in their propensity to enhance akathisia, as well as possible sex differences.

Adult↗
PubMed1995

Complete reversion and prevention of rectal adenomas in colectomized patients with familial adenomatous polyposis by rectal low-dose sulindac maintenance treatment. Advantages of a low-dose nonsteroidal anti-inflammatory drug regimen in reversing adenomas exceeding 33 months.

PURPOSE: This nonrandomized, controlled Phase II pilot study aims at the lowest effective dose of rectally applied sulindac to achieve and maintain adenoma reversion in colectomized patients with familial adenomatous polyposis (FAP). METHODS: The study group (n = 15) underwent proctoscopic and laboratory follow-up for polyp reversion every 6 to 12 weeks. Polyp reversion was followed by dose reduction in predefined steps. Proliferating cell nuclear antigen/cyclin (PCNA) and KI-67 proliferation indices (PI) were performed by point counting. Prostaglandin (PG)E2 and PGF2 alpha were quantified by time-resolved competitive fluorescence immunoassay. RESULTS: All patients responded to therapy within 6 to 24 weeks. Sixty and 87 percent of patients achieved complete adenoma reversion after 48 weeks at 53 and 67 mg of sulindac per day per patient on average, respectively. Reversion was evident compared with the control group. Dose reduction by one-sixth to one-eighth of the usual oral dose was significant (Mann's trend test, P < 0.05). PCNA and KI-67 PIs of adenomatous and flat mucosa were significantly reduced (Wilcoxon's test, P < 0.05). Correlation of PCNA and KI-67 PIs indicate similar reaction of different tissue structures (Spearman's rank correlation test, P < 0.01). Nonsteroidal anti-inflammatory drug-induced redifferentiation from high-grade to low-grade dysplasia occurred in all but two patients. Tissue-PGE2 levels were greatly reduced. Unwanted, curable side effects were rare (gastritis, n = 2), and laboratory controls are within detection limits. CONCLUSIONS: Low-dose rectal sulindac maintenance therapy is highly effective in achieving complete adenoma reversion without relapse in 87 percent of patients after 33 months. Rectal FAP phenotype should be crucial for the surgical decision. Colectomy with ileorectal anastomosis and regular chemoprevention might proceed to be a promising alternative to pouch procedures. Chemoprevention with lower incidence of FAP-related tumors via dysplasia reversion may be possible in the future.

Adenomatous Polyposis Coli↗
PubMed1997

Prostaglandin E1 infusion compared with prostacyclin infusion in patients with refractory heart failure: effects on hemodynamics and neurohumoral variables.

Prostaglandin E1 or prostacyclin were randomly infused in 18 patients with severe chronic heart failure who did not respond to oral treatment. Maximally tolerated dosages of both agents increased cardiac index; however, only prostacyclin decreased mean arterial pressure and increased plasma norepinephrine significantly. Twelve hours after 50% peak dose reduction, atrial natriuretic peptide levels, right atrial pressure, mean pulmonary artery pressure, and mean arterial pressure continued to decrease with prostaglandin E1, whereas the increase in cardiac index was sustained; in contrast, at 50% prostacyclin dose reduction, cardiac index decreased toward baseline, suggesting that, with reduced dosages for chronic infusions, desired hemodynamic changes seem to be sustained with prostaglandin E1 only.

Alprostadil↗
PubMed1991

Cholinergic blockade with pirenzepine induces dose-related reduction in glucose and insulin responses to a mixed meal in normal subjects and non-insulin dependent diabetics.

OBJECTIVE: The aim of the study was to assess the effects of cholinergic blockade with pirenzepine on glucose and insulin responses to a mixed meal in normal subjects and patients with non-insulin dependent diabetes (NIDDM). Further, to assess in normal subjects the relative importance of nocturnal GH suppression by pirenzepine. DESIGN: Placebo, 100 or 200 mg pirenzepine were given to the normal subjects 1 hour before a standard mixed meal. The effects of placebo or 200 mg pirenzepine at night on nocturnal GH secretion and subsequent breakfast carbohydrate tolerance were also studied. NIDDMs were given placebo or 200 mg pirenzepine before the meal. SUBJECTS: We studied six healthy male volunteers (ages 20-22, body mass indices 20.3-23.3) and ten NIDDMs (eight men, ages 42-74); five obese (BMI 25.5-31.8) and five non-obese (BMI 21.2-24.8). MEASUREMENTS: Serial plasma glucose and insulin concentrations were measured for 3 hours after a standard mixed meal. RESULTS: Acute pretreatment of normal male volunteers with pirenzepine produced a dose-related improvement in carbohydrate tolerance. Peak post-prandial plasma glucose levels were delayed and significantly reduced following 200 mg orally (6.5 +/- 0.1 mmol/l), but not following 100 mg (7.3 +/- 0.3), compared with placebo (7.6 +/- 0.3). Peak insulin levels were similarly delayed and reduced by the 200 mg dose only (36.5 +/- 6.1 mU/l, compared with 49.8 +/- 8.7). Suppression of nocturnal GH by 200 mg pirenzepine at night produced a small reduction in fasting plasma glucose (5.0 +/- 0.1 mmol/l, compared with 5.3 +/- 0.1, P less than 0.02) but did not improve subsequent breakfast carbohydrate tolerance. Peak plasma glucose in NIDDMs was reduced following pirenzepine (12.4 +/- 0.9 mmol/l) compared with placebo (14.3 +/- 1.0, P less than 0.01). This reduction was equally significant in obese and non-obese groups. Peak plasma insulin was also reduced by pirenzepine (22.4 +/- 3.9 mU/l) compared with placebo (42.4 +/- 5.3, P less than 0.01). Insulin suppression was quantitatively greater in obese than in non-obese patients. CONCLUSIONS: Improvement in carbohydrate tolerance after pirenzepine in normal subjects is dose related and largely independent of GH suppression. Cholinergic blockade can also improve meal carbohydrate tolerance with simultaneous reduction in plasma insulin concentrations in non-insulin dependent diabetics, particularly those with obesity.

Adult↗
PubMed1999

Dose dependent reduction of erythroid progenitor cells and inappropriate erythropoietin response in exposure to lead: new aspects of anaemia induced by lead.

OBJECTIVE: To determine whether haematopoietic progenitor cells and erythropoietin (EPO), which is an essential humoral stimulus for erythroid progenitor (BFU-E) cell differentiation, are affected by lead intoxication. METHODS: In male subjects chronically exposed to lead with and without anaemia, pluripotent (CFU-GEMM), BFU-E and granulocyte/macrophage (CFU-GM) progenitor cell counts in peripheral blood were measured with a modified clonal assay. Lead concentrations in blood (PbB) and urine (PbU) were measured by the atomic absorption technique, and EPO was measured with a modified radioimmunoassay. RESULTS: PbB in the subjects exposed to lead ranged from 0.796 to 4.4 mumol/l, and PbU varied between 0.033 and 0.522 mumol/l. In subjects exposed to lead with PbB > or = 2.896 mumol/l (n = 7), BFU-E cells were significantly reduced (p < 0.001) whereas the reduction in CFU-GM cells was only of borderline significance (p = 0.037) compared with the age matched controls (n = 20). The CFU-GEMM cells remained unchanged. Furthermore, BFU-E and CFU-GM cells were reduced in a dose dependent fashion, with increasing PbB or PbU, respectively. In the subjects exposed to lead EPO was in the normal range and did not increase in the presence of anaemia induced by lead. No correlations existed between EPO and PbB, PbU, or progenitor cells. CONCLUSION: The data suggest new aspects of lead induced anaemia besides the currently acknowledged shortened life span of erythrocytes and inhibition of haemoglobin synthesis. Two additional mechanisms should be considered: the reduction of BFU-E cells, and inappropriate renal EPO production in the presence of severe exposure to lead, which would lead to an inadequate maturation of BFU-E cells.

Adult↗
PubMed2005

Skin toxicity associated with pegylated liposomal doxorubicin (40 mg/m2) in the treatment of gynecologic cancers.

OBJECTIVES: To characterize the incidence of skin toxicity of pegylated liposomal doxorubicin (PLD) administered at a lower dose (40 mg/m(2)) in the treatment of advanced gynecologic malignancies. METHODS: Medical charts of all patients who initiated PLD at a starting dose of 40 mg/m(2) from 1997 to 2003 for the treatment of gynecologic cancers were retrospectively reviewed. PLD was infused over 1-2 h and administered every 4-6 weeks. No patient had previously received doxorubicin. All patients were clinically assessed for adverse reactions including skin toxicity. RESULTS: Ninety patients (mean age 62 years, range 45-82 years) were included in this analysis. There were 55 ovarian, 16 endometrial, 2 fallopian, and 17 primary peritoneal cancers. The median cumulative dose of PLD was 120 mg/m(2) (range 40-855 mg/m(2)) with a median of 3 cycles (range 1-25). 33/90 (37%) developed a skin reaction during therapy. The overall incidence of grade 1, 2, and 3 skin toxicity was 23 (26%), 9 (10%), and 1 (1%), respectively. Of the 23 cases of grade 1 toxicity, 16 (70%) occurred within 1-3 cycles. All 9 cases of grade 2 toxicity occurred within 1-3 cycles. The only case of grade 3 toxicity occurred after the first cycle. 28/30 (93%) patients who continued treatment did not experience further episodes of skin toxicity with subsequent cycles after a dose reduction (5-20 mg/m(2)). PLD was stopped in only 2/90 (2%) cases due to a skin reaction. CONCLUSIONS: Severe skin toxicity (> or =grade 2) associated with PLD occurs infrequently when initial doses of 40 mg/m(2) are administered. When skin reactions appear, they usually occur early in the course of treatment, respond to dose reduction, and do not appear to limit the duration of treatment.

Aged↗
PubMed2005

Sirolimus-associated interstitial pneumonitis in solid organ transplant recipients.

Sirolimus is a potent immunosuppressive agent used with increasing frequency in solid organ transplantation (SOT). However, it has been associated with rare but devastating pulmonary toxicity. We describe a case of pulmonary toxicity associated with the use of sirolimus in a 64-yr-old heart transplant recipient. We also review all reported cases of sirolimus-associated lung toxicity among SOT recipients in an effort to better understand the pathophysiology, risk factors, and outcomes of this rare but serious complication. A total of 64 cases have been reported since January 2000 including the present case. These consisted of 52 kidney, four lung, three liver, three heart, one heart-lung and one islet cell transplants. In most cases, patients presented with a constellation of symptoms consisting of fever, dyspnea, fatigue, cough, and occasionally hemoptysis. Although the risk factors for this association have not been clearly established, high dose, late exposure to the drug and male gender have been noticed among most. In almost all of the reported cases, sirolimus was added later in the course of immunosuppressive therapy, usually in an effort to attenuate the nephrotoxic effects of a previous regimen containing a calcineurin inhibitor. There were three deaths (4.8%) among 62 patients with known status at follow up; all deaths were among heart transplant recipients. Most patients (95%) resolved their clinical and radiographic findings with discontinuation or dose-reduction of the drug. Sirolimus-induced pulmonary toxicity is a rare but serious entity that should be considered in the differential diagnosis of a transplant recipient presenting with respiratory compromise. Dose-reduction or discontinuation of the drug can be life saving.

Bronchoscopy↗
PubMed1994

Tolerance of patients with human immunodeficiency virus and anal carcinoma to treatment with combined chemotherapy and radiation therapy.

PURPOSE: To evaluate treatment tolerance in patients with and without the human immunodeficiency virus (HIV) who were undergoing treatment of anal cancer. MATERIALS AND METHODS: The authors retrospectively reviewed the medical records of 62 patients with anal cancer who received radiation treatment. Seven patients had HIV, four of whom had acquired immunodeficiency syndrome. Fifty-five patients were HIV negative, including 11 patients identified as being at high risk for HIV infection whose status was unknown. RESULTS: Thirty of the 55 (55%) patients who were HIV negative required treatment breaks of a mean duration of 16.7 days. Four of those 55 (7%) patients required hospitalization. Three of 42 (7%) patients who were HIV negative receiving chemotherapy required chemotherapy dose reduction. All seven patients with HIV required treatment breaks of a mean duration of 21.7 days. Three of the seven (43%) patients required hospitalization. Four of the seven (57%) patients required chemotherapy dose reduction. CONCLUSION: Patients with HIV undergoing treatment of anal cancer have increased toxic reactions to chemoradiation. Treatment must be individually tailored on the basis of extent of disease and degree of compromise of the immune system.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Effect of age on therapeutic outcome in advanced diffuse histiocytic lymphoma: the Southwest Oncology Group experience.

To study the influence of chronologic age on treatment outcome in patients with advanced, diffuse large-cell (histiocytic) lymphoma (DHL), we reviewed the results of two recent Southwest Oncology Group (SWOG) clinical trials. From 1974 to 1982, members entered 307 eligible patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without bleomycin, and CHOP with or without immunotherapy using BCG, levamisole, or both. Complete response (CR) rates declined progressively with advancing age: 65% in those under 40, 60% in the 40 to 54 age group, 55% in the 55 to 64 age group, and 37% in those 65 and older (P = .001). Likewise, survival decreased significantly in older patients: medians were 101 +, 52, 34, and 16 months, respectively (P less than .001). Treatment guidelines included an initial dose reduction of 50% for patients aged 65 or older and for younger patients with bone marrow compromise. Despite protocol specifications, 23 of 81 patients aged 65 or older received initial full-dose therapy. When these patients were compared with younger patients on whom full-dose chemotherapy was started, survival curves, but not CR rates, were still significantly different. There were no significant differences in duration of CR or frequency of treatment complications. These data suggest that older age is associated with a worse prognosis in advanced DHL. Moreover, the initial dose reduction for patients aged 65 or older may have contributed to their inferior outcomes.

Adult↗
PubMed1985

De novo hemolytic uremic syndrome in renal transplant recipients immunosuppressed with cyclosporine.

Three renal transplant recipients were studied who developed the hemolytic uremic syndrome (HUS) during cyclosporine (CsA) immunosuppression. All patients displayed characteristic findings including normocytic, normochromic anemia, thrombocytopenia, erythrocyte morphologic abnormalities, increased numbers of reticulocytes, bone marrow hyperplasia, and renal failure. The clinical studies support the diagnosis of an extrinsic hemolytic process. Renal biopsy specimens demonstrated fibrin deposition and glomerular thrombosis. The renal failure was not responsive to antirejection therapy. The first patient was converted to azathioprine and consequently had a gradual improvement in renal function. Failure to convert the second patient resulted in adequate immunosuppression and subsequent graft loss. The third patient's improvement corresponded with a moderate CsA dose reduction. The occurrence of HUS in these patients represents a de novo presentation after CsA immunosuppression. An analysis of these cases indicates that CsA should be discontinued if HUS persists after moderate dose reduction.

Adult↗
PubMed2004

Feasibility of high-dose interferon-alpha2b adjuvant therapy for high-risk resected cutaneous melanoma.

The Kirkwood high-dose interferon-alpha2b adjuvant therapy in high-risk-of-recurrence melanoma patients (stage IIb-III) demonstrated a benefit in terms of disease-free survival (DFS) (three trials out of three) and overall survival (OS) (two trials out of three). These important and exclusive results match with a grade 3-4 toxicity in about 75% of patients. This problem is the most limiting of this treatment. The aim of the study was to check these results and the feasibility of this treatment using the original Kirkwood schedule of 52 weeks, with appropriate dose modification, until unacceptable toxicity or progression of disease. From 23rd February 1998 until 29th July 2002, 26 patients were treated (mean age 45 years; range 25-70) with high-dose interferon-alpha2b adjuvant therapy. All patients were evaluated for toxicity, whilst 24 out of 26 (92%) were evaluated for OS and DFS. All patients were in stage IIB/III of the new American Joint Committee on Cancer (AJCC) classification. The sentinel node biopsy was performed in 19 out of 26 (73.1%) patients (clinical N0). At 31st December 2002, 20 out of 26 (77%) were still alive, whilst four (15%) had died and two (8%) were lost to follow-up. Of the patients still alive, 14 (70%) were disease free. The patients lost to follow-up refused to continue therapy for toxicity related treatment: one of them was disease free, whereas one was relapsed. There were 11 observed relapses (44%). The DFS ranged from 2 to 27 months. Among the patients, the maximal DFS is, at the time of writing, 59 months. The DFS mean is 29 months, the median is 19 months. The OS calculation will be performed at the end of 5 years observation. Now our attention is on therapy tolerability. In 18 patients out of 26 (69%) we noted at least one grade 3-4 toxicity, in accordance with literature data. The most common toxicities were haematological, hepatic, fever and asthenia. Overall, only two grade 4 events (one hepatic and one haematological) were reported. Grade 3 toxicity was hepatic in 23% of patients and haematological in 50%. Grade 2 toxicity was hepatic in 19%, haematological in 27% and fever in 50%. Grade 1 toxicities were hepatic, haematological and fever in 15, 15 and 35% of patients, respectively. Asthenia was severe in 54%, mild in 31% and not found in 15%. In 39, 4 and 15%, respectively, we have reported no hepatic, haematological or fever events. Less common toxicities were nausea, diarrhoea, headache, arthralgia, alopecia and one case of hypothyroidism. As a result of these reported toxicities, of 23 patients evaluable with regard to the protocol, 12 underwent dose reductions, six suspended treatment for disease progression, eight delayed treatment for toxicity, two interrupted treatment indefinitely for unacceptable toxicity or refused treatment, two refused to continue, two patients had no delay in treatment and three did not receive any delay or dose reduction. Of three patients still in therapy, just one has so far received a delay in treatment. Overall, only four patients (17%) interrupted therapy for toxicity related events, whereas 83% continued with the expected program: 52 weeks of therapy with appropriate dose modifications.

Adult↗
PubMed1990

Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen.

A prospective study was performed to evaluate the feasibility of full dose chemotherapy given on schedule in elderly patients with unfavourable non-Hodgkin's lymphoma, stage IE, III and IV. Using a combination regimen of six courses of cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) given every 4 weeks, no serious toxicity was encountered in a group of 30 consecutive patients with a mean age of 70.4 years. A 60% complete response rate was observed and a total response rate of 90%. The disease-free survival of complete responders was 50% at 1 year. The overall survival was also 50% at 1 year. In 148 courses of CNOP only two serious infectious episodes were noted, i.e. one herpes zoster infection and one case of bronchopneumonia. Asymptomatic transient thrombocytopenia and granulocytopenia were commonly observed. Nadirs of white blood cells were WHO grade 1, 2, 3 and 4 in six, five, twelve and two patients respectively and nadirs of thrombocytopenia were WHO grade 0 and 1 (22 patients) or 2 (three patients). Based on low white blood cell counts, a delay of 1 week before administration of the next course of CNOP was necessary in 7% of the courses. No dose reductions were applied. Toxicity other than transient granulocytopenia was minor and consisted of alopecia and nausea. WHO grade 0-2. CNOP related toxicity was never a reason to stop treatment. It is concluded that CNOP chemotherapy without initial dose reduction in elderly patients with intermediate and high grade malignant non-Hodgkin's lymphoma is feasible and that no major toxicity is observed.

Aged↗
PubMed1989

Dose-dependent reduction by Ro 15-4513 in mice of the effects of ethanol and some other general depressant drugs.

In mice, Ro 15-4513 reduced the anaesthesia induced by ethanol and some other general depressant drugs, but was less effective against others. The order of potency was, from greatest reduction to least, ethanol, t-butanol, trichloroethanol, urethane, chlormethiazode, pentobarbitone. Of the two gaseous anaesthetics that were tested, ether anaesthesia was reduced but halothane was not. These results appeared independent of the doses of depressant or of Ro 15-4513; the effect of Ro 15-4513 in reducing ethanol anaesthesia was blocked by flumazenil (Ro 15-1788). It would appear that the benzodiazepine receptor complex is of importance in the induction of anaesthesia, most significantly with ethanol and to a diminishing degree with the other general depressants tested.

Anesthetics↗