Initial intravenous cis-platinum therapy: improved management for invasive high risk bladder cancer?

Between August 1981 and December 1983, 50 patients with invasive high risk bladder cancer were treated initially with 100 mg. per m.2 cis-platinum intravenously in 2 doses with a 3-week interval, which was followed by definitive treatment (radiotherapy and/or cystectomy). High risk disease was defined on the basis of at least 2 of the following: invasion into or beyond the muscle (stages B2 to D1), grade III histology, large tumors and ureteral obstruction. Major symptomatic improvement was noted in 38 patients (76 per cent) after 1 to 2 doses of cis-platinum and 30 (60 per cent) had an objective response to cis-platinum. An objective response (complete or partial remission) was noted in 43 patients (86 per cent) after cis-platinum plus definitive treatment. The 12-month actuarial survival was 86 per cent and the 2-year actuarial survival was 80 per cent (although only 14 patients were entered in the study more than 2 years ago). The protocol was well tolerated, with nausea and vomiting being the most common side effects. There were no deaths related to treatment. Ten patients (20 per cent) died of cancer. The relevance of initial cis-platinum therapy in this management program is now being evaluated in a multicenter randomized trial.     

Subsequent tumor analysis of 36 patients who have received intravesical mitomycin C for superficial bladder cancer

We studied 36 patients with stages O and A (Tis, Ta and T1) bladder cancer who had received 8 weekly doses of 30 or 40 mg. mitomycin C as definitive therapy. Of this group 16 had failed thiotepa therapy and 13 had grade III tumors (6 multifocal carcinoma in situ). The complete response rate at 12 weeks was 45 per cent (negative biopsy and cytology), while an additional 33 per cent had a partial response. Response did not correlate with tumor grade or stage. Patients who had failed thiotepa therapy were less likely to have a complete response, although the over-all response rate was identical to patients who had either not received prior chemotherapy or were not clear thiotepa failures. Followup of these patients indicates that the complete responders were benefited by this regimen since the subsequent recurrence rate was reduced when compared prior to initiation of mitomycin C. Most of these patients received monthly maintenance therapy.     

Tumors of the submaxillary gland.

This study reviews a thirty year experience with 217 patients who had a tumor of the submaxillary gland, comprising about 9 per cent of all patients with salivary neoplasms seen during the same period. Most of the tumors were malignant (56 per cent), with adenoid cystic carcinoma predominating, but the histologic type most frequently encountered was benign mixed tumor (43 per cent). Median age was fifty-four years in patients with malignant tumors compared with forty-six years in those with benign tumors, and 58 per cent were women. Asymptomatic swelling was the usual presenting complaint, and the clinical findings are summarized using a staging system recently proposed for patients with parotid tumors. Cervical lymph node metastasis occurred in at least 50 per cent of patients who had an adenocarcinoma or epidermoid, mucoepidermoid, or anaplastic carcinoma. Treatment was surgical and complete gland excision proved adequate in those with benign tumors. Radical neck dissection was performed in conjunction with submaxillary resection in most patients with malignant lesions, but radical en bloc resection was reserved for those few who had extensive or fixed disease. Net determinate "cure" rates at five and ten years (30 and 20 per cent, respectively) are distressingly low and compare unfavorably with those previously reported in patients treated for carcinoma of the parotid. The high local recurrence rate and the greater incidence in the submaxillary gland of more aggressive tumor types which metastasize readily suggest that current treatment should be more radical. It seems reasonable to expect that results might be improved if en bloc resections were more often performed in patients with less advanced disease, possibly in conjuction with intensive postoperative irradiation in selected cases.     

Progressive metastatic renal cell carcinoma controlled by continuous 5-fluoro-2-deoxyuridine infusion

We treated 19 patients with progressive metastatic renal cell carcinoma with continuous infusion of 5-fluoro-2-deoxyuridine, 52 per cent of whom had previously received and failed chemotherapy. Implantable pumps were used for automatic drug delivery. 5-Fluoro-2-deoxyuridine was infused continuously for 14 days at monthly intervals. The starting dose was 0.15 mg. per kg. per day (intravenous) or 0.25 mg. per kg. per day (intra-arterial). Intravenous doses were increased or decreased in increments of 0.025 mg. per kg. per day as permitted by toxicity. Abdominal pain, diarrhea and mucositis limited the intravenous infusion, while malaise, anorexia and hepatic function abnormalities limited intra-arterial infusion. Of 18 evaluable patients we observed 1 complete, 4 partial (objective response rate 28 per cent) and 2 minor responses. The duration of response ranged from 2 to greater than 18 months. During a median follow up of 7.5 months (range 2 to 21 months) only 4 of the 18 patients had objective tumor progression. Over-all survival for the 19 patients was 94 per cent. Continuous infusion of 5-fluoro-2-deoxyuridine may be effective for the treatment of progressive renal cell carcinoma.     

Intra-arterial cisplatin for bladder cancer

Cisplatin (25 to 120 mg. per m.2) was injected into the internal iliac arteries of 33 patients with locally advanced bladder cancer. Of the patients 9 were inevaluable for response to the cisplatin, since they began radiotherapy to the bladder before course 2 of cisplatin as part of a preplanned therapeutic approach. One patient received the treatment as postoperative adjuvant therapy, 1 did not return for followup and 1 with metastatic disease did not undergo repeat cystoscopy. Of 21 evaluable patients 3 (14 per cent) achieved complete remission, 12 (57 per cent) achieved partial remission, 2 (14 per cent) were stable and 4 (19 per cent) failed. The response rate was higher in patients receiving 100 to 120 mg. per m.2 per course than in patients receiving lower doses (all except 1 of whom received 60 or less mg. per m.2 per course) (86 versus 64 per cent) and it was higher in patients without prior radiotherapy or chemotherapy. The response rate in patients with previously untreated invasive transitional cell carcinoma was 88 per cent. Of the 33 patients 21 were alive at last followup, with a median duration of followup of 32 weeks. Toxicity was dose-related and local neurotoxicity was excessive at cisplatin doses of 100 to 120 mg. per m.2. Diabetic patients were particularly prone to have neurotoxicity. Other toxicity generally was not severe and consisted of ototoxicity, nephrotoxicity, myelosuppression, nausea, vomiting and diarrhea. Even elderly patients and patients with cardiac disease tolerated the treatment well. We plan to proceed with further intra-arterial cisplatin studies in which all patients except those more than 80 years old will be treated with an intra-arterial cisplatin dose of 90 mg. per m.2 per course combined with radiotherapy with or without cystectomy.     

Intravesical doxorubicin for prophylaxis in the management of recurrent superficial bladder carcinoma

Intermittent intravesical doxorubicin chemotherapy was given to 27 patients with multiple recurrent superficial transitional cell carcinoma of the bladder, including 12 who had become refractory to intravesical thiotepa. The starting dose was 60 mg. doxorubicin diluted in 40 to 50 ml. normal saline solution and doses were increased to 90 mg. The duration of instillation was 60 minutes. Treatments were administered every 3 weeks for a total of 8 doses, then every 6 weeks for 2 doses and then every 12 weeks for 2 doses. Therapy then ended for patients who were rendered free of disease. Cystoscopy and urinary cytology studies were performed every 3 months throughout the study. Of the patients 30 per cent had intermittent episodes of dysuria, 26 per cent had urinary frequency, 41 per cent had hematuria and 15 per cent had bladder spasms. None of these toxicities required discontinuation of the drug. Analysis of plasma samples for doxorubicin and metabolites revealed no systemic absorption and there was no myelosuppression. Of the 27 patients 15 (56 per cent) have maintained complete eradication of bladder cancer without any evidence of residual carcinoma detected endoscopically or with urinary cytology. Recurrent disease developed in 9 patients (33 per cent) while on therapy, including 3 with muscle invasion. Cystoscopy has remained grossly negative in 3 patients who have had positive class 5 cytology studies. The median duration of followup in all patients has been 12 months, with a range of 6 to 24 months. We conclude that intravesical doxorubicin is tolerated well and is effective in the management of multiple recurrent superficial transitional cell carcinoma of the bladder.     

Primary tumors of the small bowel

Primary tumors of the small bowel are uncommon, representing less than 6 per cent of all gastrointestinal tumors and less than 2 per cent of all malignant gastrointestinal tumors. This report concerns a twenty-five year survey of our clinical records from 1946 to 1971 which revealed 140 primary small bowel tumors, excluding periampullary tumors. Fifty-two of the neoplasms (37 per cent) were benign; eighty-eight (63 per cent) were malignant and included twenty-eight adenocarcinomas (31.8 per cent), twenty-four lymphosarcomas (27.3 per cent), nineteen carcinoids (21.6 per cent), and ten leiomyosarcomas (11.4 per cent). The average age at the time of diagnosis was 56.9 years for patients with benign tumors and 55.9 years for those with malignant tumors. The illusive and obscure nature of small bowel tumors is illustrated by the fact that 63.3 per cent of patients with benign lesions and 47.6 per cent of those with malignant lesions had symptoms for more than six months before the diagnosis was made. Bleeding was the most common present complaint in patients with benign neoplasms (52.9 per cent) whereas patients with malignant lesions more often had symptoms of obstruction (50.6 per cent). Most of the benign lesions were located proximally in the small bowel (duodenum, 34.6 per cent; ileum, 11.5 per cent), and most of the malignant lesions were located distally (duodenum, 17.0 per cent; ileum, 61.4 per cent). Treatment of patients with malignant lesions was radical excision whenever possible. Adjunctive radiation therapy was used for those with lymphoma. A second benign or malignant tumor occurred in 42.9 per cent of the patients with primary small bowel tumors. The average period of survival after diagnosis of a malignant small bowel tumor was 5.03 years: for patients with adenocarcinoma, 3.6 years; lymphosarcoma, 1.3 years; carcinoid, 6.8 years; and leiomyosarcoma, 8.3 years.     

Cardiovascular responses to diazepam and midazolam maleate in the dog.

Previous clinical studies establishing the efficacy of midazolam maleate (RO 21-3981), a new water-soluble benzodiazepine for induction of anesthesia, have not critically evaluated the effects of this agent on the cardiovascular system. The present study compares the cardiovascular effects of midazolam maleate and diazepam in conscious dogs. Systemic arterial, pulmonary arterial and central venous pressures, cardiac output, LVmax dP/dt, heart rate and regional coronary blood flow were measured 3 min following intravenous administration of diazepam (0.5, 1.0, and 2.5 mg/kg) or midazolam maleate (0.25, 1.0, and 10.0 mg/kg). Midazolam maleate increased heart rate 10--20 per cent with all three doses and decreased mean arterial blood pressure approximately 10--20 per cent at 1.0 and 10 mg/kg. Cardiac output was increased 10--12 per cent with all three doses of midazolam maleate, and LVmax dP/dt was decreased 13--16 per cent at the two higher doses. Diazepam at all three doses did not alter heart rate or mean arterial blood pressure. Diazepam, 1.0 and 2.5 mg/kg, produced significant (17 per cent) decreases in LVmax dP/dt, and 2.5 mg/kg produced a significant (10 per cent) increase in cardiac output. Neither drug in any dosage altered regional coronary blood flow, systemic or coronary vascular resistance, stroke volume, or stroke work. Maximum alterations in cardiovascular variables occurred with doses of midazolam maleate that are 10--15 times the recommended clinical induction dosage. It is concluded that in concentrations necessary for induction of anesthesia midazolam maleate has minimal effects on cardiovascular function.     

A multicenter, double-blind, trimethoprim-sulfamethoxazole controlled study of enoxacin in the treatment of patients with complicated urinary tract infections

In a double-blind, randomized, controlled trial, 249 patients with complicated urinary tract infections received either 400 mg. enoxacin or 160 mg. trimethoprim plus 800 mg. sulfamethoxazole orally every 12 hours for 14 days. The clinical outcome at the end of treatment revealed that all 89 evaluable patients (100 per cent) in the enoxacin group and 88 of 90 (98 per cent) in the trimethoprim-sulfamethoxazole group had satisfactory clinical responses (cure or improvement). Bacteriological effectiveness was measured cumulatively based on responses during and at the end of treatment, and 7 days later at followup. Satisfactory bacteriological responses (eradication or superinfection at all evaluations throughout the study) were achieved in significantly more (p equals 0.03) patients treated with enoxacin (93 per cent) than in those treated with trimethoprim-sulfamethoxazole (83 per cent). Both study medications were well tolerated. These results indicate that oral enoxacin was more effective clinically and bacteriologically (the latter statistically so) than trimethoprim-sulfamethoxazole when given as empiric therapy in the treatment of complicated urinary tract infections.     

Low molecular weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis

Three consecutive randomized open studies have been carried out to determine the optimal dosage of low molecular weight heparin (LMWH) in the prevention of postoperative thrombosis in general surgery (892 patients). All patients undergoing abdominal, gynaecological, thoracic or urological surgery were over 40 years old and presented at least one of the following risk factors for thrombosis: previous thromboembolism, obesity, varicose veins, malignancy (30 per cent), pre-operative hospitalization over 5 days, oestrogen therapy, chronic cardiac disease or bronchitis. Isotopic venous thrombosis and bleeding complications were assessed after subcutaneous administration of a LMWH fragment (LMWH, Enoxaparine) or unfractionated heparin (UH). The three studies compared 3 X 5000 units UH daily with 1 X 60 mg, 1 X 40 mg, 1 X 20 mg LMWH daily. Thromboembolic events rates were not significantly different from group to group (UH: 3.8 per cent, 2.7 per cent, 7.6 per cent respectively compared with LMWH: 2.9 per cent, 2.8 per cent, 3.8 per cent). Bleeding episodes including wound haematoma formation, perioperative blood losses and systemic haemorrhage were not significantly different in patients receiving LMWH or UH. Significant decreases in haematocrit and haemoglobin were only observed in patients receiving 60 mg Enoxaparine (as compared to UH). An analysis using the 'intention to treat' approach gave results consistent with those of an analysis of good compliers. An overview of isotopic thromboses in the three studies gave no evidence of differences amongst the effects of the three doses of LMWH (P = 0.20), and pooling the results of the three studies using the Mantel-Haenszel procedure gave no evidence of a global difference between Enoxaparine and UH (P = 0.54). These results suggest that an optimal dosage of 20 mg/day of Enoxaparine is safe and effective in the prevention of postoperative thrombosis in this population.     

Tissue plasminogen activator in peripheral arterial thrombolysis

Thirty acute peripheral arterial thromboses in 28 patients were treated with local low-dose intra-arterial recombinant tissue plasminogen activator (t-PA). All patients received 0.5 mg h-1 t-PA and 15 also received 250 units h-1 of intra-arterial heparin. Overall limb salvage at 30 days was 83 per cent (25 out of 30 limbs). Mean(s.d.) ankle/brachial index was increased by 0.53(0.26) and there was no significant difference between the group receiving t-PA alone and that receiving t-PA and heparin. No strokes or major haemorrhages occurred but there were four (13 per cent) minor haematomas associated with the catheter entry site. There were four (13 per cent) deaths from myocardial infarction occurring between 5 and 21 days after treatment. Rethrombosis occurred in four cases (13 per cent). In two patients following t-PA alone, rethrombosis occurred after 2 and 11 days. Limb salvage was achieved with a successful repeat thrombolysis and a femoropopliteal graft respectively. Rethrombosis after t-PA and heparin occurred after 30 days in two patients due to poor run-off and extensive proximal atheromatous disease respectively. t-PA is a safe, effective thrombolytic agent when given as a low-dose intra-arterial infusion. The addition of low-dose heparin does not produce any significant benefit.     

Epidural morphine for analgesia after Caesarean section: a report of 4880 patients

This retrospective study was undertaken to assess the efficacy and safety of epidural morphine in providing analgesia following Caesarean section under epidural anaesthesia. The morphine was administered as a single bolus, following delivery, in doses ranging from 2 to 5 mg. The charts of 4880 Caesarean sections, performed on 4500 patients, were reviewed. The duration of analgesia and the occurrence of any symptoms which might be side-effects of the epidural morphine were recorded. The duration of analgesia was 22.9 +/- 10.1 hr and was not correlated with the dose of epidural morphine. Eleven per cent of the patients required no supplemental analgesia during the first 48 hr. Twelve patients (0.25 per cent) had respiratory rates less than 10 breaths per minute, on at least one occasion. No serious sequelae resulted from these periods of bradypnoea. Pruritus occurred in 58 per cent of patients, nausea and vomiting in 39.9 per cent and dizziness in ten per cent. Herpes simplex labialis was recorded in 3.5 per cent of patients. Epidural morphine is thus confirmed as an effective analgesic technique post-Caesarean section with 3 mg being the optimal dose. Even in this young healthy patient population, clinically detectable respiratory depression occurs so clinical respiratory monitoring is indicated.     

Adjuvant medroxyprogesterone acetate and steroid hormone receptors in category M0 renal cell carcinoma. An interim report of a prospective randomized study

From July 1, 1979 to June 30, 1983, 136 consecutive patients with category M0 renal cell cancer who had undergone transperitoneal radical nephrectomy at 5 centers entered a prospective randomized trial to compare 500 mg. adjuvant medroxyprogesterone 3 times a week for 1 year to no treatment. Sex steroid hormone receptors also were studied in the renal tumor and in the surrounding healthy parenchyma with the dextran-coated charcoal technique. After a median followup period of 3 years (range 13 to 60 months) 30 of 121 evaluable patients (24.8 per cent) experienced relapse, usually in the lung or bones. Relapses occurred in 15 of 58 evaluable patients in the adjuvant treatment group (25.8 per cent) and 15 of 63 evaluable controls (23.8 per cent). The disease recurred more frequently (35.1 per cent) in the 57 patients with no receptors in the tumor than in the 45 with at least 1 receptor (17.8 per cent). These results were independent of adjuvant therapy. After a median 3-year followup, adjuvant medroxyprogesterone acetate was of no therapeutic benefit in patients who had undergone radical nephrectomy and the side effects of the therapy were evident in more than 50 per cent of the patients.     

Bladder cancer in men and women treated by radiation therapy and/or radical cystectomy

Four-hundred fifty-one patients with bladder cancer, 348 men and 103 women, were treated by radiation therapy and/or radical cystectomy during the last two decades at Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was the treatment in 98 men and 39 women. Radical radiation therapy to an average tumor dose of 6,000 rad in six weeks was given to 79 men and 30 women ± one year before salvage cystectomy was done for recurrent or persistent tumors. Planned preoperative irradiation was delivered to the true pelvis either 4,000 rad in four weeks in 95 men and 24 women or 2,000 rad in one week in 76 men and 10 women ± six weeks and two days, respectively, before radical cystectomy. Over-all survival and recurrence results in both sexes were similar; 40 per cent of men and 36 per cent of women were alive at five years without recurrence, 45 per cent of men and 48 per cent of women died in five or more years with local and/or distant recurrences, and 21 per cent of men and 15 per cent of women died before five years from causes other than cancer recurrence. Higher five-year survival for high clinical stage B₂ to D₁ tumors was noted similarly in the irradiated men (30 per cent) and women (37 per cent) than in the cystectomy alone patients (19 per cent in men and 4 per cent in women). Similar survival rates (52 to 57 per cent) were observed in men and women with low clinical stage O to B1 tumors treated with or without irradiation.     

Neostigmine,pyridostigmine and edrophonium as antagonists of deep pancuronium blockade

To compare the ability of equipotent doses of neostigmine, pyridostigmine and edrophonium to antagonize intense pancuronium neuromuscular blockade, one hundred and twenty ASA physical status I or II patients scheduled for elective surgery received 0.06 mg.kg-1 pancuronium during a thiopentone nitrous oxide-enflurane anaesthetic. Train-of-four stimulation was applied every 12 s and the force of contraction of the adductor pollicis muscle was recorded. In the first 60 patients, spontaneous recovery was allowed until ten per cent of initial first twitch height. Then neostigmine (0.005, 0.01, 0.02 or 0.05 mg.kg-1), pyridostigmine (0.02, 0.04, 0.1 or 0.2 mg.kg-1), or edrophonium (0.1, 0.2, 0.4 or 1 mg.kg-1) was injected by random allocation. Dose-response relationships were established from the measurement of first twitch height (T1) ten minutes later. From these, neostigmine, 0.04 and 0.08 mg.kg-1 was found to be equipotent to pyridostigmine, 0.2 and 0.38 mg.kg-1, and edrophonium, 0.54 and 1.15 mg.kg-1, respectively. These doses were given by random allocation to the next 60 patients, but at one per cent spontaneous recovery. Neostigmine, 0.04 mg.kg-1, produced a T1 of 73 +/- 4 per cent (mean +/- SEM), and a train-of-four ratio (TOF) of 39 +/- 3 per cent. This was significantly greater than with pyridostigmine, 0.2 mg.kg-1 (T1 = 50 +/- 6 per cent; TOF = 25 +/- 3 per cent), and edrophonium, 0.54 mg.kg-1 (T1 = 54 +/- 3 per cent; TOF = 17 +/- 2 per cent).(ABSTRACT TRUNCATED AT 250 WORDS)     

Time course of antirecall effect of diazepam and lorazepam following oral administration

The time course of antirecall effect and grades of sedation after the oral administration of diazepam and lorazepam were determined in 120 patients. Three standard doses of each drug were employed. Grades of sedation following oral diazepam were dose related, with a latency of 30-60 min and duration of 120-150 min. All three doses of lorazepam produced significantly more sedation with a similar latency (30-60 min) but longer duration (more than 240 min). Peak frequencies of the antirecall effects of diazepam 10, 15, and 20 mg were 5, 20, and 30 per cent, respectively. The duration was about two hours. Peak frequencies of the antirecall effect after lorazepam 2, 3, and 4 mg were 30, 45, and 72 per cent, respectively. Latency of peak action was about 60-90 min for all the doses, but the duration, especially with 3 and 4 mg doses, was long (4 h).     

Hypertension following coronary artery bypass graft

Hypertension following coronary surgery is generally reported at an alarmingly high incidence (30 to 75 per cent). A vigilance program carried out in 1977 at the Montreal Heart Institute disclosed a low incidence of 3.5 per cent in 200 consecutive unselected cases. A similar program in 1980 based on 160 cases showed an incidence of 23.7 per cent. This highly significant difference is found to be related to the differences in anaesthetic management which have occurred since 1977 when anaesthesia was primarily morphine 1.0 to 1.5 mg . kg-1 supplemented as needed with low dose halogenated agents and vasodilation therapy. In 1980, only one of the authors (J.T.) still uses this technique. The incidence of hypertension in 40 of his patients was 2.5 per cent. The others use low dose fentanyl (7.5 to 10 micrograms . kg-1) supplemented as needed with halogenated agents and vasodilating therapy; the incidence of hypertension in 160 cases was 23.7 per cent. Would these results be the same with an anaesthetic technique comparing both drugs at equipotent doses? A prospective clinical study is addressing this question.     

A comparison of nalbuphine and meperidine in treatment of postoperative pain

The analgesic efficacy and side effect profile of nalbuphine 20 mg IV and of nalbuphine 40 mg IV were compared to those of meperidine 75 mg IM in the immediate postoperative period. Pain intensity, pain relief, additional analgesic requirements and the overall acceptability of the treatment were recorded for 150 patients. No significant differences were found between the groups for any of the efficacy variables. Peak analgesic effects occurred at 15 minutes in both nalbuphine groups and at 30 minutes in the meperidine group. The mean time to additional analgesic medication was approximately 207 minutes in each group. The incidence of nausea and vomiting with meperidine was 22 per cent (95 per cent confidence interval 10 to 34 per cent) and with nalbuphine 20 mg the incidence was two per cent (95%CI -2 to 6 per cent). This difference was significant (p less than 0.01). The difference between nalbuphine 40 mg (10 per cent, 95%CI 1 to 19 per cent) and meperidine, was not considered statistically significant (p = 0.17). The analgesic efficacy of nalbuphine 20 mg was indistinguishable from that of nalbuphine 40 mg and from that of meperidine 75 mg. The significantly lower incidence of nausea and vomiting with nalbuphine is a major advantage for a recovery room analgesic.     

A comparative evaluation of intubating doses of atracurium,d-tubocurarine,pancuronium and vecuronium in children

To determine the onset and recovery times and haemodynamic effects of intubating doses of atracurium (0.4 mg.kg-1), d-tubocurarine (0.8 mg.kg-1), pancuronium (0.12 mg.kg-1), and vecuronium (0.07 mg.kg-1), sixty-seven children aged one to eight years were studied under halothane and nitrous oxide anaesthesia. The time to maximum twitch depression and the time to recovery to T1/Tc 25 per cent were recorded with an integrated evoked EMG recorder. The heart rate and systolic blood pressure were recorded for five minutes after drug administration and prior to intubation. There was no difference in onset times between drugs. The recovery time to T1/Tc 25 per cent following vecuronium (25.5 +/- 6.3 min) was shorter than following atracurium (37.5 +/- 7.0 min). Recovery times for d-tubocurarine and pancuronium were greater than sixty minutes. Elevation of heart rate occurred after administration of pancuronium (+29.8 per cent to +38.6 per cent) and d-tubocurarine (+31 per cent to +34.9 per cent), but no change was observed after atracurium or vecuronium. Elevation of blood pressure was greatest following pancuronium (+10.8 to +14.8 per cent). No significant change was observed following atracurium or vecuronium. A transient lowering of blood pressure (-9.3 per cent) occurred following d-tubocurarine.     

Dosage and duration of tamoxifen treatment for mastalgia: a controlled trial

A controlled trial has been conducted in which 60 women with mastalgia were randomly allocated to receive tamoxifen at a dosage of either 10 mg or 20 mg daily for either 3 or 6 months. All eligible patients had self-rated moderate or severe mastalgia present for at least 6 months, for which no specific therapy had been given for the previous 3 months. End points of the study were pain control, measured by linear analogue scales, relapse rate and side-effects. Pain relief was achieved in 90 per cent of those receiving 10 mg daily and 86 per cent of those given 20 mg daily. The relapse rate was also similar for both dosages, being 48 per cent and 39 per cent respectively and usually occurred within 2-3 months of discontinuing treatment. However, side-effects were reported less frequently among those receiving 10 mg daily (21 per cent versus 64 per cent; chi 2 = 11.1, P less than 0.001). Prolongation of treatment from 3 months to 6 months did not materially improve the response rate (85 per cent versus 90 per cent). Side-effects were similar, as was the relapse rate among the patients receiving the two durations of treatment. The agent proved to be significantly more effective in the relief of cyclical rather than non-cyclical pain (94 per cent versus 56 per cent). Use of tamoxifen for the treatment of mastalgia is still experimental. Nevertheless, for the majority of women with mastalgia, pain relief can be achieved using tamoxifen 10 mg daily, given for a 3-month course. As almost half these patients will develop relapse of breast pain it may be necessary to give longer courses of therapy, although the safety of this more protracted treatment has yet to be determined.