Prospective evaluation of pulmonary function in cancer patients treated with total body irradiation, high-dose melphalan, and autologous hematopoietic stem cell transplantation.

Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: a) cyclophosphamide (7 g/m2); b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed.

Total body irradiation and high-dose melphalan with bone marrow transplantation at Istituto Nazionale Tumori, Milan, Italy.

The technique of total body irradiation (TBI) developed at Istituto Nazionale Tumori, Milan, Italy, is described. This technique consists of i) administration of 12.5 Gy and 14.85 Gy TBI for autologous and allogeneic bone marrow transplantation respectively; ii) in all cases in vivo dosimetry of absorbed TBI dose; and iii) radiation doses to lungs higher than previously described. As of June 1988, seventeen patients with Hodgkin's disease and four with lymphoblastic lymphoma received TBI and 120-180 mg/m2 melphalan. Respiratory function was prospectively evaluated demonstrating moderate and transient reduction of pulmonary function.

Contralateral breast cancer after limited surgery plus radiotherapy of early mammary tumors.

Conservative treatment of early breast cancer with limited surgery requires a mandatory irradiation of the affected breast, which implies a low but measurable irradiation of contralateral breast too. As ionizing radiations can produce an oncogenic effect on mammary tissues, the series of 701 patients of the Milano clinical trial on T1 No breast cancer (1973-1980) was investigated to compare the incidence of contralateral breast cancer in the Halsted group (not irradiated) and in the QU.A.RT. group (irradiated on the operated breast with a total dose of 50 Gy plus a limited boost of 10 Gy). In March 1986, a contralateral breast cancer was diagnosed in 17/349 patients (4.9%) of the Halsted group and in 18/352 patients (5.1%) of the QU.A.RT. group after a median follow-up of 108 months. The sites of contralateral cancer were superimposable in the two groups of patients, with a constant prevalence of external quadrants, despite the great difference of dose distribution in the irradiated patients. Our data on the incidence of contralateral breast cancer failed to demonstrate an oncogenic effect of irradiation to date, but the follow-up is still in progress and any future event will be registered and discussed.

Severe postpartum hypertension and reversible cerebral angiopathy associated with ergot derivative (methergoline) administration.

A 36-year-old woman (gravida 2, para 2) delivered a healthy child by cesarean section at the 37th week of an unremarkable gestation. Blood pressure remained within normal range throughout the pregnancy, surgery, and for the 9 following days. On day 10, about 36 hours after the initiation of oral methergoline to suppress lactation, the patient complained of severe posterior headache, flashing scotomata, hypertension, tonico-clonic seizures and then homonymous left hemianopsia and hemiparesis. Blood pressure monitoring confirmed intermittent and severe hypertension. Angiography demonstrated diffuse narrowing of the small and medium cerebral arteries. Transcranial Doppler ultrasound examination disclosed a bilateral increase in mean flow velocity. Progressive normalization of blood pressure, obtained with labetalol and oral clonidine, was accompanied by amelioration of the neurological deficits until a complete recovery and normalization of transcranial Doppler flow velocity occurred. This case provides further evidences that hypertension might play a major pathogenetic role in reversible cerebral angiopathy. Some ergot derivatives (including methergoline) might trigger the initial rise in blood pressure.

Magnesium and cardiovascular drugs: interactions and therapeutic role.

Numerous experimental, epidemiological and clinical studies have pointed out a relevant role for magnesium deficiency in the development of many cardiovascular diseases. Some pharmacological treatments may interfere with magnesium turnover, and magnesium deficiency may alter the pharmacokinetics and pharmacodynamics of some cardiovascular drugs. Loop and thiazide-like diuretics increase magnesiuresis, and total bodily magnesium deficiency may appear during prolonged treatment with diuretically active doses of these drugs. The potassium retaining agents, such as amiloride, triamterene and spironolactone, tend to retain magnesium but they are not magnesium-retaining substances to the extent to which they are potassium-retaining diuretics. The interaction between magnesium and digitalis is complex. Magnesium, acting as an indirect antagonist of digoxin at the sarcolemma Na(+)-K(+)-ATPase pump, reduces cardiac arrhythmias due to digoxin poisoning. Recent controlled studies have shown that treatment with magnesium significantly reduces the frequency and complexity of ventricular arrhythmias in digoxin-treated patients with congestive heart failure without digoxin toxicity. Magnesium improves the efficacy of digoxin in slowing the ventricular response in atrial fibrillation. Digoxin reduces tubular magnesium reabsorption, and in patients with congestive heart failure this interaction may be cumulative with other causes of magnesium deficiency (diuretics, diet, poor intestinal absorption). The complex and potentially life-threatening interactions between magnesium and some cardiovascular drugs suggest that magnesium status should be carefully monitored in patients receiving such drugs. Therapy with magnesium is rapidly acting, has a safe toxic-therapeutic ratio, is easy to administer and titrate. The correction of magnesium deficit should therefore always be considered for patients with cardiopathy.

Prolonged treatment with ursodeoxycholic acid for primary biliary cirrhosis.

Eighteen patients affected with biopsy-proved primary biliary cirrhosis (PBC) (histological stage III and IV) received ursodeoxicholic acid (UDCA) 600 mg for 1 year. Signs and symptoms and biochemical tests (glutamic and oxalcetic transaminase, glutamic and pyruvic transaminase, bilirubine, gamma-glutamyl transpeptidase, alkaline phosphatase, leucine aminopeptidase, bile acids, plasma proteins electrophoresis, immunoglubulins A, G and M) and antimitochondrial antibodies were evaluated before the treatment and every four months during the treatment. The results were compared with those obtained in 8 untreated patients affected PBC. The control group of patients were comparable (as far as age, histological stage, biochemical tests are concerned) to the group who received UDCA. Bilirubine, ALP, gamma-GT and LAP decreased during the treatment with UDCA and remained lower than baseline values until the end of the observation (12 months), while no changes occurred in the untreated patients. Both in the treated and untreated group plasma protein electrophoresis, serum immunoglubulins A, G and M remained unchanged, as well as anti-mitochondrial antibody. A moderate reduction of transaminases and bile acids was observed in the group of patients receiving UDCA but it did not reach statistical significance. In 16 out of the 18 treated patients pruritus disappeared and resulted diminished in the remaining 2 patients. No significant amelioration of pruritus was observed in the patients who did not receive UDCA. In conclusion, our data show that prolonged treatment with UDCA drastically reduces pruritus and improves cholestasis biochemical tests in patients affected with symptomatic PBC.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-dosage ibopamine treatment in progressive renal failure: a long-term multicentre trial.

A multicentre trial (11 nephrology centres) was carried out to test the effects of ibopamine, an orally active dopamine-like drug, on the progression of chronic renal failure. For a 2-year period 189 chronic renal failure patients (serum creatinine level 1.5-4.0 mg/dl) were observed. They were homogeneous for basic nephropathy, degree of residual renal function, blood pressure, and proteinuria. The patients were randomly divided into two groups: 96 took ibopamine at a dosage of 100 mg/day (group A) and 93 served as controls (group B). All were on a low-protein diet (mean 0.8 g/kg body weight). By the end of the observation period, the rate of decrease of the renal function indexes in time proved significantly slower (1.8 times) in group A than in group B. The survival curves for renal function (pre-established end points were creatinine level increases equal to or > 20% and equal to or > 40% of the basal values) proved significantly better (p < 0.02 and p < 0.002 respectively) in group A than in group B. The mean plasma creatinine values rose by 17% in group A and by 36% in group B. The creatinine clearance decreased by 5% in treated patients and by 14% in the controls. Statistical analysis ruled out any possible centre effect. The trial suggests that low-dosage ibopamine administration may be used as a valid and safe pharmacological adjunct for retarding the progression of renal failure in patients with mild or moderate chronic renal impairment.