24-hour pH monitoring in symptomatic patients without erosive esophagitis who did not respond to antireflux treatment.

Twenty symptomatic patients without erosive esophagitis underwent 24-h esophageal pH monitoring after failing standard medical antireflux treatment. Sixty-five percent had abnormal esophageal acid exposure, and the majority of these improved on proton pump inhibitor therapy. However, 35% had a normal 24-h pH test. One patient had coronary artery disease, one had diffuse esophageal spasm, and two had a negative work-up and no improvement with omeprazole. Consequently, we suggest that patients like these have an omeprazole trial. If symptoms persist, 24-h esophageal pH monitoring can appropriately define more rational management. Patients with abnormal esophageal acid exposure will require more aggressive acid-control therapy, whereas those with normal esophageal acid exposure will need further work-up to assess the cause of their symptoms.

The challenge of detection and management of alcohol abuse among elders.

Alcohol abuse and dependence, defined in the Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised), is a serious mental health problem in older adults. It affects an estimated 2.5 million older adults. The true extent of alcohol abuse and dependence among elders is likely even greater as many problem drinkers go undetected. Alcohol abuse can seriously predispose the elderly to accidents, nutritional deficiencies, and diseases, and eventually result in loss of independence. The purpose of this article is to (1) describe the profile of older alcoholics in the acute care setting who typically mask as medical management seekers, (2) relate some of the difficulties involved in accurately identifying the problem of elder alcohol abuse, and (3) suggest strategies to improve intervention by CNSs.

Age- and gender-related differences in 24-hour esophageal pH monitoring of normal subjects.

Twenty-four-hour esophageal pH monitoring is currently the most sensitive test for diagnosing gastroesophageal reflux. Little is known, however, about the effect of aging and gender on esophageal acid exposure in asymptomatic individuals. Thirty asymptomatic volunteers underwent 24-hr esophageal pH monitoring. Fifteen were < 65 years (eight female, seven male) and 15 were > or = 65 years (seven female, eight male). In this asymptomatic group no significant difference was seen by age, while males were found to have significantly more esophageal acid exposure than females. The need for sex-specific normal 24-hr pH monitoring values is suggested. Thirty percent of these asymptomatic subjects were abnormal by conventional 24-pH criteria. The clinical importance of these "silent refluxers" is unknown.

Phase II trial of bisantrene in non-small cell lung cancer.

Eighteen evaluable patients with non-small cell lung cancer (NSCLC) were treated with bisantrene at a dose of 200 mg/m2 once a week for 3 consecutive weeks. Courses of treatment were repeated every 4 weeks. This dose schedule caused leukopenia (less than 3,500 cells/microl) in all patients. There were no objective responses in 18 patients. Bisantrene in this myelosuppressive dose schedule did not have significant activity in patients with NSCLC.

Pharmacology of mitoxantrone: mode of action and pharmacokinetics.

Although a number of investigators have established that mitoxantrone (Novantrone; dihydroxyanthracenedione) inhibits RNA and DNA synthesis and intercalates with DNA in vitro, its exact mechanism of action is unclear. Mitoxantrone is structurally related to a series of substituted anthraquinones and has features known to be essential for DNA intercalation; however, we have determined recently that mitoxantrone binds DNA in intact L1210 leukemia cells by a non-intercalative, electrostatic interaction and induces both protein associated and non-protein associated DNA strand scissions. The difference between mitoxantrone and doxorubicin with respect to their interactions with DNA could account for their relative lack of cross-resistance in the treatment of lymphoma and acute leukemia. Distribution and half-life data provide a pharmacological rationale for the use of mitoxantrone on an intermittent dosing schedule. Considerable evidence exists to suggest that mitoxantrone undergoes extensive metabolism, probably in the liver. Preliminary data show that abnormal liver function leads to decreased rates of total body mitoxantrone clearance, suggesting a possible need for dose reduction in patients with severe liver dysfunction. The most important route of mitoxantrone elimination appears to be fecal. Because of the relatively low urinary excretion it is unlikely that the standard drug dose must be reduced in the presence of compromised renal function.

Phase II trial of bisantrene in patients with intermediate and high grade diffuse non-Hodgkin's lymphomas.

Sixteen heavily pretreated patients with advanced intermediate and high-grade diffuse non-Hodgkin's lymphoma (NHL) were treated with 260 mg/M2 of bisantrene every three weeks. Thirty infusions of bisantrene were given without evidence of objective response. Pain in the infused arm, with or without signs of phlebitis, was the most common side effect occurring in 40% of treated patients. At the doses employed bisantrene had little activity as a single agent in this group of previously treated patients with unfavorable histology NHL.

Prospective study of left ventricular function using radionuclide scans in patients receiving mitoxantrone.

A prospective Phase II study to evaluate the effects of mitoxantrone on left ventricular ejection fraction (LVEF) has been carried out in patients treated with 12 mg/m2 every three weeks. Gated radionuclide cardiac blood pool imaging with assessment of LVEF and wall motion prior to and during graded exercise was performed before the first and every other mitoxantrone course. Ten patients had either a minor response or tumour stabilization while receiving mitoxantrone treatment and underwent serial radionuclide scans during the course of therapy. Three patients who had received adriamycin as part of prior chemotherapy regimens showed no evidence of cardiotoxicity. Seven patients, who had had no prior adriamycin exposure, underwent serial radionuclide studies while receiving up to 204 mg/m2 of mitoxantrone. None of these patients showed evidence of clinically significant myocardial damage. One had a decline in LVEF from 70% to 50% at a maximum dose of 108 mg/m2. An additional patient whose LVEF rose from 57% at baseline to 62% at a total dose of 204 mg/m2 (17 courses) underwent endomyocardial biopsy which showed grade 2.5 anthracyclin-type cardiotoxicity. Serial endomyocardial biopsy studies are indicated in patients on longterm drug therapy to determine the incidence, dose-relationship and severity of potential mitoxantrone associated endomyocardial damage.

Scalp hypothermia: a comparison of ice packs and the Kold Kap in the prevention of doxorubicin-induced alopecia.

Two methods of scalp hypothermia were compared in preventing alopecia, a side effect of doxorubicin chemotherapy that has a significant psychologic impact on the patient. Thirty-three patients received scalp ice packs consisting of crushed ice in plastic bags. Twenty-nine patients received Kold Kap, a device that produces chilling via an endothermic reaction. Scalp hypothermia was applied for 5-10 min before the doxorubicin bolus and left in place for 30-40 min afterward. The percent of hair loss was rated at each visit and photographs were used to further quantitate any hair loss. Sixty-three percent of Kold Kap and 56% of ice pack patients had good or better protection and did not require wigs. Excellent protection (less than 25% loss) was provided for 51% of Kold Kap and 33% of ice pack patients. Similar protection was provided to Kold Kap patients regardless of dose, while ice pack patients received significantly better protection if their doxorubicin doses were less than 50 mg. Scalp hypothermia is an effective method of preventing doxorubicin-induced alopecia.

Phase I clinical investigation of 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] dihydrochloride with correlative in vitro human tumor clonogenic assay.

9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] dihydrochloride (bisantrene) is a new anthracene bishydrazone derivative which was entered into a Phase I clinical trial (one dose weekly for 3 weeks) because it showed significant antitumor activity in a number of animal tumor models and in vitro in the human tumor stem cell assay. When possible, patients were entered into the phase I study if their tumors showed in vitro sensitivity to bisantrene and resistance to standard agents, using a human tumor stem cell assay. Thirty-one patients were treated with bisantrene over a 10-month period, starting at a dose of 70 mg/sq m/week. The appearance of leukopenia determined the dose-limiting toxicity of bisantrene. The maximally tolerated dose appeared to be 200 mg/sq m in that three of five patients tolerated these weekly-for-3-weeks doses while experiencing only mild or moderate leukopenia. In contrast, the 220-mg/sq m dose caused moderate to life-threatening leukopenia after just two weekly doses in four of five patients. Local bisantrene toxicity included mild to severe arm swelling, phlebitis, pain, urticaria, and erythema in 68% of the patients. In general, these toxicities were well tolerated and rapidly reversible, but two patients had severe local swelling for up to 6 months. In this Phase I trial, bisantrene showed clinical antitumor activity against both hematological cancer (i.e., lymphoma and myeloma) and solid tumors (i.e., bladder, lung, and renal cancer and melanoma). Of importance, four of the six responses occurred in patients whose therapy was selected on the basis of in vitro sensitivity to bisantrene using the human tumor stem cell assay. One patient with disseminated melanoma had complete disappearance of an axillary node metastasis (for more than 6 months) while developing a brain metastasis, suggesting that bisantrene does not concentrate in the central nervous system.