Practical management of patients with non-small-cell lung cancer treated with gefitinib.

PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.     

Effect of dietary protein on Masheri-induced drug metabolising enzymes

The modulation of drug metabolising enzymes by Masheri extract (ME) and Benzo(a)Pyrene [B(a)P] was studied in male Sprague Dawley rats fed different dietary protein levels. Two groups of 21 days old male Sprague Dawley rats were put on a high protein diet (SHP) with 20% Casein, and a low protein diet (SLP) with 3% Casein semisynthetic based diets for 12 weeks. The SLP fed animals showed lower basal levels of the Phase I activating enzymes viz. Cytochrome P450, Benzo(a)Pyrene hydroxylase, Benzphetamine demethylase and Phase II glutathione detoxification system viz. Glutathione (GSH) and Glutathione-S-transferase. ME and B(a)P treatment significantly depleted the glutathione detoxification system in the SLP group whereas an opposite effect was observed in the SHP group. Interstingly, ME and B(a)P treated rats in the SLP group showed a higher percent increase in the hepatic and pulmonary Phase I enzyme activities than those observed in the treated ME/B(a)P treated SHP rats. Furthermore, both ME and B(a)P significantly decreased the hepatic pool of vitamin A while a concomittant increase in that of vitamin C was observed.     

Hepatic candidiasis in cancer patients: the evolving picture of the syndrome

Focal hepatosplenic candidiasis has been recognized with increasing frequency in recent years. We reviewed the cases of eight patients seen between 1982 and 1985, and information on 60 patients whose cases have been reported in the world literature. The characteristics of focal hepatosplenic candidiasis include persistent fever in a neutropenic patient whose leukocyte count is returning to normal, often coupled with abdominal pain; an elevated alkaline phosphatase level; and less commonly, rebound leukocytosis. The characteristic "bull's eye" lesions seen with hepatic ultrasound examination or computed tomography generally are not detectable until neutrophil recovery has occurred. Diagnosis can be established only by biopsy evidence of yeasts or pseudohyphae in the granulomatous lesions. Cultures are frequently negative, however, especially in patients who have been pretreated with antifungal agents. We review the evolving nature of hepatosplenic candidiasis, focusing on diagnosis and treatment.     

Correlates of Control in Pediatric Cancer Patients and Their Families

Physical illness is a life experience which challenges an individual'ssense of control and thus represents a potential threat to mentalhealth. For children, a serious illness threatens not only theirsense of physical and psychological well-being but also threatensthe psychological well-being of their family. In this study,severely ill patients (n = 15) and a member of their family(n = 15) were interviewed. The patients, who ranged in age from12 to 21 years, were being treated for metastatic solid tumorsor lymphoma that failed to respond to conventional therapeuticregimens. Correlates of control for the patients and familymembers, the relationship between control and developmentalstage of the patients, and the difference between levels ofcontrol in patients and family member were examined. The findingsare discussed in relation to development and their implicationsfor medical management.     

Endoscopic retrograde stenting for allograft hydronephrosis

BACKGROUND AND OBJECTIVES: Ureteral obstruction occurs in 2% to 10% of all renal transplant recipients. Antegrade endourologic intervention has been the gold standard of therapy but carries significant morbidity. This study was designed to investigate the feasibility of retrograde stenting of these difficult ureters and to determine whether it can be performed with minimal morbidity without general or regional anesthesia. METHODS: Ninety-seven consecutive patients were found to have renal allograft hydronephrosis by ultrasonography, between August 1993 and March 1997. Of these, 61 (63%) had confirmation of obstruction by MAG-3 imaging, with equivocal results in 25 (26%). The remaining 11 patients had a rising creatinine concentration despite Foley catheter drainage. All patients had retrograde stenting attempted under local anesthesia followed by intravenous sedation if necessary. If stent placement was unsuccessful, the procedure was repeated under regional or general anesthesia. RESULTS: A total of 85 patients (88%) were managed successfully with retrograde stenting. Of these procedures, 24 (28%) were performed under local anesthesia alone, while 57 (67%) required both local anesthesia and intravenous sedation. Only 4 patients (5%) required general anesthesia. No patient suffered any morbidity associated with retrograde stenting. Of the 12 patients in whom retrograde stenting failed, 2 had renal allograft rupture and 10 had ureteral necrosis at surgical exploration. CONCLUSIONS: Retrograde stenting of the hydronephrotic renal allograft can be achieved with a high success rate and minimal morbidity, usually without general or regional anesthesia. If the ureter cannot be managed in a retrograde fashion, a high index of suspicion for a serious allograft complication should exist.     

Characterization of lymphoma-derived cell lines: comparison of cell lines positive and negative for Epstein-Barr virus nuclear antigen. I. Physical, cytogenetic, and growth characteristics

Sixteen lymphoid cell lines were derived from patients with undifferentiated lymphoma of Burkitt's or non-Burkitt's type. They were obtained directly from tumor biopsies, from serous effusions, or from bone marrow. In 10 of the cell lines, the Epstein-Barr virus (EBV) nuclear antigen (EBNA) was undetectable; the remaining 6 lines were EBNA-positive (EB-pos). Of the 16 lines, 15 were aneuploid, with detectable chromosome "14q+ markers (11 had +8;14 translocations). These 15 lines, which included the EBNA-negative (EB-neg) lines, were believed to be of tumor cell origin. The remaining line consisted predominantly of diploid cells derived from normal lymphocytes, but some cells of tumor origin were present. Four EB-pos cell lines derived from EB-neg tumors had an aneuploid karyotype consistent with an origin from tumor cells (including no.8;14 translocation in two), which suggested that either tumor cells were infected with EBV in vitro or a tiny fraction of EB-pos tumor cells (or potential tumor cells) present in vivo gave rise to the predominant cell of the line. EB-neg B-cell lines and EB-pos cell lines established from undifferentiated lymphomas differed greatly. EB-neg lines had consistently smaller electronic mean cell volumes and narrow-angle light scatter than did EB-pos lines. This finding correlated with a lower nuclear:cytoplasmic ratio in EB-pos lines. EB-neg lines also had higher saturation cell densities than did EB-pos lines under standard culture conditions. The data indicate either that EBV influences the morphologic and physiologic characteristics of lymphoid cell lines or that EB-neg B-cell lines and EB-pos cell lines are derived ultimately from different lymphocyte subpopulations or that both may apply.     

Arthroscopic treatment of anterolateral impingement of the ankle

We studied 31 patients (17 females, 14 males; average age, 34) with more than 2 years of followup who had chronic anterolateral ankle pain following inversion injury. All had failed to respond to at least 2 months of conservative treatment and had negative stress radiographs to rule out instability. On physical examination, tenderness was localized to the anterolateral corner of the talar dome. Magnetic resonance imaging was the most useful diagnostic screening test, showing synovial thickening consistent with impingement in the anterolateral gutter. At an average of 24 months after injury, all patients underwent ankle arthroscopy, which showed proliferative synovitis and fibrotic scar tissue in the lateral gutter, often with associated chondromalacia of the talus. Operative arthroscopic treatment consisted of partial synovectomy with debridement of scar tissue from the lateral gutter. Postoperatively, patients walked with crutches allowing weightbearing as tolerated. Average return to sports was 6 weeks. Histopathologic analysis performed on the resected tissue showed synovial changes consistent with chronic inflammation. Results of treatment after at least 2 year followup were 15 excellent, 11 good, 4 fair, and 1 poor. Since there are several distinct causes of chronic ankle pain, we prefer to call this problem "anterolateral impingement of the ankle" and believe the term "chronic sprain pain" should be discarded.