Pulmonary resection for lung cancer in HIV-positive patients with low (<200 lymphocytes/mm(3)) CD4(+) count

The clinical improvement obtained with combination treatment has modified the therapeutic approach of lung cancer in HIV-positive patients. Aggressive surgical treatment has become a viable option for those patients in whom the CD4(+) cell count was greater than 200 lymphocytes/mm(3). We recently extended our surgical indications to include two HIV-positive patients with lung cancer (stage IIIA and IIB) and low (<200 lymphocytes/mm(3)) CD4(+) count. Both patients underwent a lobectomy and mediastinal nodal dissection. The postoperative course was uneventful. No evidence of recurrent cancer was seen at 12 and 20 months after the operation. Based on this limited experience, we conclude that a low CD4(+) count should not represent, per se, an exclusion criterion for the surgical treatment of pleuropulmonary conditions in HIV-positive patients.     

Autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma: comparison of different parameters in predicting the kinetics of haematological recovery

We analysed the kinetics of haematological recovery after autologous bone marrow transplantation (ABMT) in 31 patients with non-Hodgkin's lymphoma, of whom 14 had received chemotherapy and 17 had received no chemotherapy before marrow harvesting. The time for recovery of polymorph (PMN) and platelet numbers was assessed in relation to patient's sex, age, the numbers of mononuclear cells (MNC) and of granulocyte-macrophage colony-forming cells (CFU-GM) reinfused, the therapy before harvesting and the conditioning regimens. The results showed that the most important factor influencing the speed of haematological recovery was therapy before marrow collection; recovery was faster in patients not treated before harvesting than in those treated. The mean day for PMN recovery to 0.5 x 10(9)/l was 14.6 vs 21.8 (p less than 0.001); the mean day for platelet recovery to 50 x 10(9)/l was 16.5 vs 44.4 (p less than 0.00002). The other parameters assessed did not correlate with the kinetics of haemopoietic recovery. We conclude that NHL patients who undergo ABMT without chemotherapy prior to marrow harvest have rapid haematological recovery, which suggests that better timing of the harvest could be of value in the management of NHL patients for whom 'reinforcement' with ABMT is scheduled.     

Plant lectins as carriers for oral drugs: is wheat germ agglutinin a suitable candidate?

Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed also by gastrointestinal epithelial cells. WGA is currently investigated as an anti-tumor drug and as a carrier for oral drugs. Information on whether it can cross the gastrointestinal epithelium and on its possible effects on the integrity of the epithelial layer is however scanty or lacking, and herein we address these issues. Differentiated Caco2 cells have been used as a model of polarized intestinal epithelium. WGA concentration at both the apical and the basolateral side of the epithelium has been quantified using a sensitive ELISA assay (sensitivity threshold 0.84 nM). Trans epithelial electrical resistance (TEER) has been measured to evaluate the integrity of the epithelium upon treatments with WGA. (3)H-Mannitol (182.2 Da) and FITC-dextran (3000 Da) have been used to measure the permeability of the epithelium. Cell viability has been measured by the MTT, by 7-AAD uptake, and Annexin-V binding assays. Up to a concentration of 5.6 microM, approximately 0.1% of intact WGA molecules only could cross the epithelial layer. WGA perturbed the integrity of the epithelium and increased the permeability of the tissue in a dose- and time-dependent manner. WGA did not induce cell death but increased the permeability of individual cells to 7-AAD which is normally not uptaken by viable cells. These data allowed us to define a toxicity threshold for WGA on epithelial cells. WGA suitability as a carrier for oral drugs can therefore be evaluated on a rational basis.     

Magnitude of right-to-left shunt as the only determinant of stroke in a pair of identical twins

Abstract. Right-to-left shunt due to patent foramen ovale is a well-established risk factor for stroke in the young. The magnitude of shunt seems to be correlated to the risk of stroke in individuals. We report the cases of two 51-year-old identical twins, with similar risk factors for ischemic stroke, in which the sibling with a large and permanent shunt suffered a left hemispheric stroke and the other, with a small and latent shunt, was asymptomatic. In a three-year follow-up, the siblings were both asymptomatic, and the dimensions of shunts were unchanged. Our cases stress the importance of quantifying right-to-left shunt in order to stratify the risk of stroke in individuals, and suggest a role of heredity in patency of foramen ovale.     

A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

In this multicentre, double-blind study, patients with LUTS/BPH were randomised to 26 weeks with finasteride 5 mg once daily (n=204) or tamsulosin 0.4 mg once daily (n=199). Double-blind treatment was continued for another 26 weeks (total treatment duration: 1 y). The primary efficacy parameter was the difference in mean change in total Symptom Problem Index (SPI) from baseline to end point at week-26 in the intention-to-treat (ITT) and per protocol (PP) populations. Tamsulosin induced a greater improvement in total SPI (-5.2 points or -37%) compared to finasteride (-4.5 points or -31%) at week-26 (P=0.055 in ITT and P=0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more bothersome storage symptoms) and flow more quickly than finasteride. The difference was statistically significant for the SPI from week-1 (reduction, respectively, -2.5 vs -1.8 points, P=0.043) to week-18 and for Qmax from week-1 (increase, respectively, 2.3 vs 0.7 ml/s, P=0.0007) to week-12. Both treatments were well tolerated with a comparable incidence of adverse events, including urinary retention.     

Feasibility of peritonectomy associated with intraperitoneal hyperthermic perfusion in patients with Pseudomyxoma peritonei

AIMS AND BACKGROUND: Pseudomyxoma peritonei is a rare disease characterized by a complete redistribution of mucin within the peritoneal cavity. It can be classified into three histologic groups: disseminated peritoneal adenomucinosis, peritoneal mucinous carcinomatosis, and an intermediate group. The aim of the present study was to evaluate the feasibility of cytoreductive surgery requiring peritonectomy procedures associated with intraperitoneal hyperthermic perfusion, a technique that combines hyperthermia and high drug doses administered locally. METHODS: Twenty-seven patients with pseudomyxoma peritonei (19 males and 8 females) were enrolled in a phase II clinical trial. Twenty-two cases underwent cytoreductive surgery plus intraperitoneal hyperthermic perfusion, and 6 received debulking surgery only. One patient was operated on twice for disease recurrence. All patients with peritoneal mucinous carcinomatosis presented serous ascites, whereas all but one patient with disseminated peritoneal adenomucinosis or in the intermediate group presented mucinous ascites. Cytoreductive surgery was performed with peritonectomy procedures. The closed abdomen technique was adopted for intraperitoneal hyperthermic perfusion using a preheated polysaline perfusate containing cisplatin (25 mg/m2/L) plus mitomycin-C (3.3 mg/m2/L) through a heart-lung pump at a mean flow of 600 mL/min for 60 mins from the hyperthermic phase (42.5 degrees C). RESULTS: All but one of the patients with disseminated peritoneal adenomucinosis and 2 of the 3 patients in the intermediate group were optimally cytoreduced. Patients with serous ascites (all patients with peritoneal mucinous carcinomatosis and 1 patient with disseminated peritoneal adenomucinosis) were considered ineligible for treatment because of tumor diffusion. The morbidity rate was 22%. There was one case of treatment-related mortality 30 days after treatment. CONCLUSIONS: The following conclusions can be drawn from this phase II clinical trial: 1) patients with pseudomyxoma peritonei originating from undifferentiated mucinous adenocarcinoma (peritoneal mucinous carcinomatosis), with complete distribution into the peritoneal cavity, are not eligible for the cytoreductive surgery plus intraperitoneal hyperthermic perfusion technique; 2) the presence of serous ascites would seem to exclude patients from the treatment; 3) cytoreductive surgery associated with intraperitoneal hyperthermic perfusion is the most suitable approach for patients with disseminated peritoneal adenomucinosis and in the intermediate group.