FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer.

PURPOSE: The chemotherapy regimens of high-dose methotrexate, high-dose fluorouracil (FU), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and leucovorin (FAMTX) and etoposide, Adriamycin, and cisplatin (EAP) have both been reported in nonrandom assignment trials to have high overall response rates and substantial complete response rates in patients with gastric cancer, as well as major toxicities of myelosuppression. Here we report a prospective, stratified, random-assignment comparison of the two combinations in previously untreated patients with advanced gastric cancer. PATIENTS AND METHODS: Sixty patients were entered onto the trial, 30 receiving EAP and 30 FAMTX. All patients had measurable or assessable tumor masses. Patient entry was stopped at the point when significant toxicity differences were seen at interim analysis. RESULTS: Response rates were similar between the two arms (FAMTX, 33% [95% confidence interval (CI), 16% to 50%]; EAP, 20% [95% Cl, 6% to 34%]). Three FAMTX and no EAP patients had complete remissions. The median survival for the two arms were similar (EAP, 6.1 months; FAMTX, 7.3 months). At 1 year, 7% of EAP and 17% of FAMTX patients were alive. EAP caused significantly more myelosuppression (leukopenia, P = .002; anemia, P = .03; thrombocytopenia, P = .0001) than did FAMTX. EAP also resulted in significantly longer hospitalizations per study month (8 v 5 days). Four EAP patients died of lethal toxicity, whereas no FAMTX patients died of treatment-related causes (P = .04). CONCLUSIONS: FAMTX is at least as active as EAP and is significantly less toxic. Although both regimens remain investigational, the toxicities of FAMTX are more manageable. Further studies involving FAMTX in both the adjuvant and advanced disease setting are underway.

Outpatient conversion of treatment to potassium-sparing diuretics.

Thiazide diuretics frequently cause a decrease in serum potassium levels. In this study, 34 percent of patients taking hydrochlorothiazide had serum potassium levels below 3.5 meq/liter. The response of the serum potassium level was studied after treatment in 56 patients was switched from 50 mg of hydrochlorothiazide daily to either two capsules of hydrochlorothiazide/triampterene (Dyazide), or one tablet of hydrochlorothiazide/amiloride (Moduretic) daily, over nine to 15 months. The 24 patients whose treatment was changed to Dyazide had a rise in serum potassium levels from a mean of 3.56 meq/liter to 4.17 meq/liter in two to three weeks. The 32 patients whose treatment was changed to Moduretic had a rise in serum potassium levels from a mean of 3.76 meq/liter to 4.14 meq/liter in two to three weeks. The resultant rise in potassium levels was stable throughout the follow-up period in both groups. Patient acceptance of this change was excellent.

Genetic analysis of alpha 2-adrenergic receptors and blood pressure using Dahl salt-sensitive rats.

OBJECTIVE: To evaluate the role of alpha 2-adrenergic receptors in genetic hypertension by cosegregation analysis using Dahl rats. DESIGN: Inbred Dahl salt-sensitive (SS/Jr) rats were crossed with inbred Dahl salt-resistant (SR/Jr) rats; also, SS/Jr rats were crossed with several control strains, and large F2 populations were subsequently produced from each cross. All F2 populations were raised on a high-salt diet. The rats were genotyped, where possible, at the loci for three different subtypes of alpha 2-adrenergic receptors designated as classes I, II and III. The blood pressures of the rats classified by genotype at each alpha 2-adrenergic receptor subtype locus were compared using analysis of variance. METHODS: Genomic clones of three classes of alpha 2-adrenergic receptors were isolated from genomic lambda-phage libraries of SS/Jr or SR/Jr rat strains, or both, by screening with complementary DNA for human alpha 2-adrenergic receptors. Fragments of the rat genomic clones obtained were used for genotyping by restriction fragment length polymorphism. Also, cloned genomic DNA flanking the alpha 2-adrenergic receptors and containing microsatellites was sequenced; genotyping at informative microsatellite markers was performed using the polymerase chain reaction. Two of the three classes of rat alpha 2-adrenergic receptors were localized to rat chromosomes by linkage analysis or using a panel of mouse-rat hybrid somatic cell lines. RESULTS: Rat alpha 2-adrenergic receptor classes I and III genes were assigned to rat chromosomes 14 and 3, respectively. These correspond to alpha 2-adrenergic receptor genes on human chromosomes 4 and 2, respectively. Extensive cosegregation analysis, involving five alleles in six segregating populations for class I alpha 2-adrenergic receptors, yielded no evidence of an effect of these loci on blood pressure. Classes II and III alpha 2-adrenergic receptors could each be tested in only one population and there was no evidence for an effect of either receptor gene on genetic differences in blood pressure. The dopamine-1B receptor was closely linked to the class I alpha 2-adrenergic receptor on rat chromosome 14. Thus, the negative cosegregation of the class I receptor with blood pressure applies equally to the dopamine-1B receptor. CONCLUSIONS: Genetic analysis in segregating populations involving crosses of inbred Dahl salt-sensitive rats with five other strains provides no evidence for a genetic effect of class I alpha 2-adrenergic receptors, or of the dopamine-1B receptor, on blood pressure. Classes II and III alpha 2-adrenergic receptors also failed to cosegregate with blood pressure but, because only limited testing was possible with the classes II and III receptors, this negative result is not definitive.

Estimate of the genetic divergence between inbred Dahl salt-sensitive and salt-resistant rats.

OBJECTIVE: The genetic divergence of inbred Dahl salt-sensitive (SS/Jr) rats from inbred Dahl salt-resistant (SR/Jr) rats and various other inbred strains was measured. DESIGN: Structural differences in DNA between strains were evaluated. METHODS: Genetic variants were sought (1) by restriction fragment length polymorphism (RFLP) analysis, using 19 DNA probes, (2) by the polymerase chain reaction around microsatellites and (3) by DNA sequencing. RESULTS: It was estimated that 1 in 1532 bases of DNA were different between the SS/Jr and SR/Jr strains. In comparing SS/Jr and SR/Jr rats, it was also observed that one DNA probe in 10 will yield multiple RFLP, presumably as the result of large insertion/deletion events. A comparison of SS/Jr rats with seven other inbred strains showed that the percentage of loci that carry alleles different from SS/Jr rats varies from about 23% for Albino Surgery rats to 71% for Brown Norway rats. CONCLUSIONS: Although the SR/Jr strain is an appropriate contrasting strain for the genetic analysis of hypertension in SS/Jr rats, a genetic analysis involving crosses of SS/Jr rats and unrelated inbred strains is also likely to be useful in identifying genes that cosegregate with blood pressure because more informative genetic markers will be available than in a cross of SS/Jr with SR/Jr rats.

Modification by prostaglandin E 2 (PGE 2 ) of the response of guinea-pig isolated vasa deferentia and atria to adrenergic stimuli.

1. Prostaglandin E(2) (PGE(2)) exerted positive cardiostimulant effects on isolated guinea-pig atria. The response was not altered by treatment of the animal with reserpine or by addition of propranolol to the organ bath. These results suggest that the cardiostimulatory actions of PGE(2) are not mediated through the release of catecholamines or stimulation of adrenoceptors.2. On the electrically driven atria, PGE(2) consistently exerted a cardiostimulant action which was not appreciably altered by changes in calcium ion in the bathing medium. PGE(2) showed no effect on the transport of calcium by the fragments of heart sarcoplasmic reticulum.3. PGE(2) reduced the responses to both noradrenaline and tyramine in the isolated atria. The shifted dose-response curve was not parallel to the original.4. PGE(2) increased the contractor response of the isolated vas deferens to nerve stimulation or to direct electrical stimulation.5. PGE(2) antagonized the increase caused by noradrenaline in contractor response of isolated vas deferens to direct electrical stimulation, whereas it affected the potentiation by noradrenaline differently when the vas deferens was contracting in response to nerve stimulation. In low concentration it inhibited and in large concentrations, it slightly enhanced the potentiation by catecholamine.6. It is concluded that PGE(2) has actions on multiple sites. It has post-junctional as well as pre-junctional effects on adrenergic neurones.

Absence of acute cocaine interactions with the MAO-B inhibitor selegiline.

Selegiline, an irreversible monoamine oxidase-B (MAO-B) inhibitor, is under investigation as a treatment for cocaine relapse prevention. To evaluate its safety, human volunteers (n = 5) received intravenous cocaine (0, 20 and 40 mg, 1 h apart) following treatment with placebo or selegiline (10 mg, p.o.). Cocaine increased heart rate, blood pressure, pupil diameter and subjective indices of euphoria and craving. Selegiline produced no measureable effects, except for miosis, and did not alter the effects of cocaine. These data suggest that selegiline may be safely administered in combination with cocaine, and that selegiline is unlikely to increase reinforcing effects of cocaine.

Canadian nurses' views on assignment of publication credit for scholarly and scientific work.

A total of 184 Canadian nurses who were expected to publish scholarly and/or scientific work or whose roles provide for socialization of nurses in academic endeavours, research, and publication were asked to respond to 42 scenarios. This study replicated, with some modifications, surveys conducted in 1981, 1985, and 1987 to determine the views of American nurses on assignment of publication credit. The scenarios in the present survey required judgements about how authorship and footnote credit should be allocated among groups involved in research and academic writing; in some scenarios all the individuals were nurses (in both clinical and academic settings), while other scenarios featured collaboration between nurses and other health-care professionals or focused on interactions between nursing professors and students. While consensus of greater than 80% was achieved for only 7 of the 42 scenarios (modal responses), the respondents' written comments revealed 2 recurrent themes: that credit should be based entirely on contribution, rather than status; and that, as much as possible, authorship and footnote acknowledgement should be discussed and resolved before contentious issues arise. There was widespread agreement on these 2 principles. However, there was disagreement concerning collaborative academic work, particularly concerning the forms of collaboration that merit authorship credit and the forms that are sufficiently acknowledged through footnoting. Both the model responses and the areas of disagreement are discussed.

Guillain-Barré syndrome. An uncommon but severe illness.

It is important for primary care physicians to be familiar with Guillain-Barré syndrome, a relatively rare disorder that may occur after another illness or after stress such as surgery. Although most patients recover fully, respiratory failure and cardiovascular failure are possible complications. Rapid diagnosis and referral to specialists experienced in plasmapheresis therapy can significantly benefit patients.

Respiratory infections in ambulatory adults. Choosing the best treatment.

The diagnosis and treatment of respiratory tract infections in ambulatory adults is challenging. The prevalence of these conditions outstrips the medical profession's efficiency and effectiveness in dealing with them. However, selecting diagnostic techniques that identify causative organisms and therapeutic agents targeted to those organisms should lead to a reduction in the morbidity and mortality associated with these illnesses.

Moving toward policy development on assigning publication credit for oncology nurses' contributions to scholarly and scientific work.

The policy implications of a 1996 national nursing survey on the allocation of publication credit form of this paper. An earlier article (Butler & Ginn, 1997) describes and analyzes the outcome of the survey; the purpose here is to draw on that analysis, and on the relevant literature, to propose a starting place for discussion within the specialty of oncology and the nursing profession regarding assignment of credit for various contributions to collaborative scholarly work. After identifying the growing need for such a discussion and briefly highlighting the findings of the survey, the paper goes on to examine unacceptable practices in scholarly work and identify issues which should be resolved before collaborative work is undertaken. The final portion of the paper makes tentative suggestions as to principles and guidelines which might be applied to avoid disputes about the value of different contributions to a collaborative project. It is emphasized that the intention is not to advocate acceptance of the guidelines suggested here, but to create sufficient interest so that an approach to allocation of publication credit may be developed which will be consistent and relevant to the needs of the nursing profession.

The northeast Tennessee Spirituality and End of Life Issues Survey.

We developed the northeast Tennessee Spirituality and End of Life Issues Survey and randomly distributed it to 1,000 patients in our internal medicine practice. We received 568 surveys at least partially completed. Most of the participants demonstrated a spiritual interest and at least half believed it appropriate for their physician to share their diagnosis and prognosis with their spiritual leader. Only 0.9% of patients thought it was necessary for their physician to know about their spiritual heritage in order to serve their needs better. Less than 30% of respondents had a living will or durable power of attorney for health care. A large majority of patients did not want CPR (67.8%) or i.v. fluids (69%) or mechanical ventilation (74.5%) if their physician determined they were at the end of their life. This was true whether or not they could identify a house of worship or a spiritual leader. Less than one-third of patients who did not want terminal CPR or mechanical ventilation had a living will or durable power of attorney for health care.

The AIDS information crisis: confluence of the roles of information creator, seeker, and provider.

The dramatic increase in the number of cases and deaths from AIDS since 1981 has been accompanied by an information explosion on the topic. The government, health professionals, service organizations, consumers, and the media are each vital links in both formal and informal AIDS information networks. New information sources and systems have emerged from these five sectors, and their roles as information creators, seekers, and providers have come together. The need for integrative or synthesizing databases and systems which reflect the sectors' interdependence and acknowledge their roles in the information process is discussed. Databases and systems which reflect a multi-sector approach, such as the Computerized AIDS Information Network (CAIN), are suggested as potential solutions to the AIDS information problem.

Cardiopulmonary resuscitation. Not for all terminally ill patients.

Where there are clear clinical indications that a patient suffering from a terminal illness would not benefit from cardiopulmonary resuscitation, there is no legal or ethical requirement that CPR be discussed with the patient as a treatment option or that CPR be administered if the patient stops breathing or suffers cardiac arrest.