Phase I study of gemcitabine and liposomal doxorubicin in relapsed ovarian cancer

Twenty-three patients were enrolled in a phase I study conducted to determine the maximum tolerated doses (MTD) of combined liposomal doxorubicin (CAE) and gemcitabine (GEM) in relapsed ovarian cancer patients. A total of 82 courses are evaluable, with a median number of three cycles administered per patient (range 2-8). GEM was administered on days 1 and 8 by 30-min intravenous infusion immediately after CAE given by 60-min intravenous infusion on day 1; cycles were repeated every 21 days. The starting doses were CAE 20 mg/m(2) and GEM 600 mg/m(2). Following dose levels were 20/800; 20/1,000; 30/800; 30/1,000; 35/800, and 35/1,000 for CAE and GEM, respectively. The MTD was reached at dose level 5, with febrile neutropenia and thrombocytopenia as dose-limiting toxicities. After the MTD, granulocyte-colony stimulating factor was administered in 15% of cycles. Non-hematological toxicity was mild and manageable. All patients are so far evaluable for response. Among them, 5 partial responses (21.7%; 95% confidence interval, CI: 4.9-38.5), 5 disease stabilizations (21.7%, 95% CI: 4.9-38.5) and 13 progressions (56.6%, 95% CI: 36.4-76.8) have been registered. These results warrant further research in a phase II study.     

Effect of repeated administration of prolactin releasing peptide on feeding behavior in rats

Prolactin releasing peptide (PrRP) has been reported to reduce food intake in rats. We tested the effect of i.c.v. administration of PrRP-31 on food intake in both food deprived and free-feeding rats. We did not find any effect of PrRP-31 on food intake after single injections of up to an 8-nmol dose, but observed a marked decrease in food intake and body weight in rats that received a repeated twice daily administration of 8 nmol of PrRP-31. This effect was associated with an adverse behavioral pattern, indicating that the repeated high doses of the peptide caused non-specific effects inducing anorexia. We also tested several other behavioral parameters like locomotion and exploratory time, grooming and resting time, using lower doses of PrRP that did not cause the adverse behavior. Moreover, we carried out locomotor and sensory motor activity tests at the doses that exerted the most pronounced effect on the food intake. None of these tests suggested any specific behavioral effect of PrRP. We conclude that the behavioral pattern induced by PrRP is likely to be different from those induced by many other neuropeptides affecting food intake in rats.     

Cardiovascular risk in hypertensive patients: results of the Pandora project

BACKGROUND: The aim of the Pandora project is to collect epidemiological information, check diagnostic and therapeutic pathways, and assess outcomes in a large hypertensive population. This report presents the results on patients enrolled in the study between 1997-1999. METHODS: Twenty-one general practitioners working in the Ravenna Local Health Service took part in the study. They were supplied with IBM compatible PCs and were trained to enter the patient's data (age, gender, familiarity for cardiovascular diseases, smoking, hospitalisations for cardiovascular disorders, diabetes, blood pressure, total cholesterolemia, creatininemia, antihypertensive therapy) on So.Ge.Pa. software. Cardiovascular risk factors were assessed according to the WHO - ISH joint committee recommendations. RESULTS: 2,608 treated hypertensive patients were enrolled, 65% of whom showed inadequate blood pressure control. The prevalence of inadequate BP control was higher in patients on multiple-drug antihypertensive therapy compared with those on monotherapy (71.9% vs. 47.9%), in older than in younger patients (70.7% vs. 56.1%) and in patients with three cardiovascular risk factors, or diabetes, or affected target organs, compared to those with two or less risk factors (72.4% vs. 63.3%), (p < 0.001 for all). 63.6% of patients were at risk for age, 36.6% for family history of cardiovascular diseases and 31.7% for severe hypercholesterolemia. CONCLUSIONS: BP control was inadequate in a large percentage of patients, but it was particularly unsatisfactory in the elderly and in patients with high cardiovascular risk. A cluster of cardiovascular risk factors was found in both adequately and inadequately controlled hypertensive patients.     

Octreotide in the Management of Bowel Obstruction in Terminal Ovarian Cancer

Intestinal obstruction is a common and distressing clinical complication in ovarian cancer. The aim of our study was to assess vomit control in terminal ovarian cancer patients with inoperable gastrointestinal obstruction, using a symptomatic pharmacological treatment with octreotide which obviates the need for nasogastric tube placement. We studied 13 patients, all of whom had advanced ovarian cancer FIGO stage IIIc. Seven patients were treated in the Gynecology Department of S. Raffaele Hospital, at the University of Milan, and 6 were managed in the University of Varese Hospital. Octreotide was administered at doses starting with 0.3 up to 0.6 mg (mean 0.44 mg) a day by subcutaneous bolus or continuous infusion. Octreotide controlled vomiting in all cases to grade 0 on the WHO emesis scale. Complete relief of symptoms was achieved within 3.07 days (range 1–6 days). Vomiting stopped within 2–3 days of starting treatment in most patients. In 8 patients with a nasogastric tube, drainage decreased from 2000 to under 100 ml/day after the start of octreotide treatment. No side effects were reported. All patients died with minimal distress or pain.     

A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome

Noonan (NS) and multiple lentigines/LEOPARD syndromes (LS) have proved to be associated with distinct PTPN11 mutations. Noonan-like/multiple giant cell lesion syndrome (NLS) is a rare disease, characterised by short stature, facial dysmorphisms, congenital heart defect (CHD) and central giant cell lesions. PTPN11 gene mutations have been reported in a single NLS family and two sporadic patients. Here we report a patient with a complex phenotype progressing throughout the years from NS at birth towards LS and NLS. PTPN11 gene analysis disclosed a novel missense mutation (Ala461Thr) in exon 12, affecting the consensus sequence of the SHP2-active site. This observation joins together NS and LS to NLS into a unique genetic defect, broadening the clinical and molecular spectrum of PTPN11-related disorders.     

Use of DDDRP pacing device in prevention and treatment of tachy-brady syndrome after Mustard procedure

A 13-year-old male patient, who underwent Mustard operation for a very complex congenital heart disease (CHD), after palliation presented a decrease of the sinus node function, developing a tachy-brady syndrome and a mild dysfunction of atrioventricular (AV) conduction. He was successfully treated using a DDDRP pacemaker, which ensured a suitable atrial rhythm and was able to interrupt supraventricular tachycardia episodes. Until now, hospitalization related to episodes of heart failure or symptomatic arrhythmia, has not been necessary.     

1-Thioangelicin: crystal structure, computer-aided studies and photobiological activity

1-Thioangelicin is a furocoumarin analog synthesized to investigate the role of the substitution of sulfur for oxygen in the parent compound angelicin. The compound was examined by X-ray diffraction, and its interaction with DNA, both in the dark and by UVA irradiation, studied by means of linear flow dichroism, chromatography and (1)H NMR. Further insight into the steric and electronic features of 1-thioangelicin has been reached through theoretical calculations, including molecular mechanics optimization, docking studies and frontier molecular orbital investigations. The experimental data indicate that thioangelicin is able to intercalate in the DNA helix and subsequent irradiation yields a cis-syn adduct, in agreement with theoretical calculations within the lower/higher singly occupied molecular orbital formalism. Antiproliferative activity has been assessed on Balb/c 3T3 cultured cells.     

Breast irradiation with three conformal photon fields for patients with high lung involvement

Since 2001, 50 breast cancer patients, for whom extensive lung/heart involvement was expected from the use of conventional tangential 2-field technique (2F) owing to complex anatomies, were irradiated using a 3-field conformal technique (3F). Dose plans were designed for both 3F and 2F and a dose volume histogram analysis on ipsilateral lung, heart, and target was conducted. The 3F technique allowed a significant reduction in ipsilateral lung irradiation: mean dose dropped from 16.0±3.8 (2F) to 12.0±2.7 Gy (3F) and V_45Gy from 20.7±6.8 (2F) to 3.2±2.9% (3F). Similarly, in patients irradiated to the left breast, heart mean dose was reduced from 8.1 Gy (2F) to 6.8 Gy (3F) and D_15% from 19.0 Gy to 14.0 Gy. All differences reached a high degree of significance. The target coverage was not clinically compromised since the slight reduction using 3F compared with 2F is limited to V_95% while V_90% difference, even if statistically significant, is small: 98.2±1.8% (3F) and 98.8±1.6 (2F). A preliminary report on clinical follow up is also included; with a mean follow up of 15.8 months, no pulmonary or cardiac complications were observed.