Effect of paroxetine hydrochloride (Paxil<Superscript>®</Superscript>) on fatigue and depression in breast cancer patients receiving chemotherapy

Summary Background. Fatigue can significantly interfere with a cancer patients ability to fulfill daily responsibilities and enjoy life. It commonly co-exists with depression in patients undergoing chemotherapy, suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue.Methods. We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy randomly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor (SSRI) paroxetine (Paxil®, SmithKline Beecham Pharmaceuticals) or an identical-appearing placebo. Patients began their study medication seven days following their first on-study treatment and continued until seven days following their fourth on-study treatment. Seven days after each treatment, participants completed questionnaires measuring fatigue (Multidimensional Assessment of Fatigue, Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist) and depression (Profile of Mood States-Depression subscale [POMS-DD] and Center for Epidemiologic Studies-Depression [CES-D]).Results. Repeated-measures ANOVAs, after controlling for baseline measures, showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D (p=0.006) and the POMS-DD (p=0.07) but not in reducing fatigue (all measures, ps > 0.27).Conclusions. Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo, indicating that a biologically active dose was used, no significant differences between groups on any of the measures of fatigued were observed. Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment.     

Surgical management of invasive breast cancer: a 5-year prospective study of treatment in the Australian Capital Territory and South-Eastern New South Wales

BACKGROUND: Breast cancer is a major health problem in Australia. The aim of the present report is to evaluate the surgical management of invasive breast cancers in our region. METHODOLOGY: As part of a multidisciplinary quality assurance project, data were collected for the majority of breast cancers treated in our region between July 1997 and June 2002. Participants included surgeons, medical and radiation oncologists, pathologists and general practitioners. RESULTS: Over the 5-year period, 1069 invasive breast cancers were treated. Mastectomy (52%) was more common than breast conservation. For cancers less than 2 cm in diameter (61%), breast conservation was achieved in 62%. High nuclear grade cancers (27%) resulted in mastectomy in 60%. This treatment pattern was the same for patients living in urban and rural areas and in all age groups. Those patients requiring two or more operations (30%) to achieve surgical clearance still had a 33% rate of breast conservation. Over the last 5 years there has been an increase in sentinel node biopsies (16 sentinel node biopsies during 1998-1999; 64 during 2001-2002) and axillary dissections started to decrease. A small group has had no axillary node biopsy or dissection, mainly patients over 70 years of age. Multimodality treatments increased over the 5-year period of our study with the use of postoperative radiotherapy increasing from 60% to 65% and chemotherapy from 36% to 55%. CONCLUSIONS: The project has mapped treatment trends for breast cancer in our region and documented the implementation of new treatment methods as well as the increasing use of multidisciplinary management, multimodality treatment and the implementation of best practice guidelines.     

Combination of aspirin and metoclopramide produces a synergistic antithrombotic effect in a canine model of coronary artery thrombosis

Summary— We compared the antithrombotic properties of low doses of aspirin (0.03, 0.1 mg kg⁻¹ intravenously [iv]) and metoclopramide (0.1, 0.3 mg kg⁻¹ iv) alone or in combination. The animal model chosen for this study involved the generation of cyclic flow variations (CFV) in the circumflex coronary artery of anaesthetized dogs as a result of a critical coronary stenosis associated with a controlled arterial lesion at the site of stenosis. Subsequent regular CFV represent sequential thrombus formation and embolization in the damaged vessel. Neither aspirin nor metoclopramide alone demonstrated antithrombotic properties at the doses tested. However, the combination of aspirin 0.1 mg kg⁻¹ iv and metoclopramide 0.3 mg kg⁻¹ iv produced a significant antithrombotic effect, reducing the frequency of large CFV from 6.7 ± 0.5 to 0.8 ± 0.4 cycles h⁻¹ ( P < 0.01) and increasing minimum mean coronary blood flow from 5.0 ± 1.1 to 23.7 ± 2.6 mL min⁻¹ ( P < 0.01). This result apparently reflects an antithrombotic synergism between aspirin and metoclopramide since the effects of the combination were greater than the combined effects of the individual treatments. The antithrombotic influence of metoclopramide could be due to its 5HT₂-antagonist or α₂-antagonist properties, both of which would inhibit platelet aggregation. This demonstration of a synergistic antithrombotic action of the combination of aspirin and metoclopramide is of interest since these two agents are often combined in clinical use. Its therapeutic relevance, however, remains to be established.     

Sepsis after coronary bypass grafting: evidence for loss of the gut mucosal barrier

Postoperative infections may originate from a patient's gastrointestinal tract. We studied infections after coronary artery revascularization. Three hundred twenty-nine patients underwent coronary artery revascularization from January 1987 to March 1990. Eight of the 329 (2.4%) died; none of the deaths were infection related. Fifty-five culture-proven infections were identified in 22 of 321 survivors (6.8%); 9 infections (16%) were gram-positive, 5 (9%) were fungal, and 41 (75%) were gram-negative. Site of infections were respiratory tract, 58%; urinary tract, 18%; blood, 13%; and mediastinum, 11%. Ninety-six percent of respiratory tract and all urinary tract infections were gram-negative or fungal. There was no significant difference between infected and noninfected groups in sex, age, smoking history, preoperative hematocrit or leukocyte count, serum albumin level, or time on extracorporeal bypass. The infected group required intubation and nasogastric suction for a significantly longer time than the noninfected group (p less than 0.001). Time to enteral alimentation was significantly longer in the infected group (p less than 0.02). We were unable to correlate the number of infections with the lengths of intubation, nasogastric suction, or time to enteral alimentation. This study supports the concept of postoperative infections arising from bacterial translocation across the patient's gastrointestinal tract. The most significant risk factor is the length of the gastrointestinal tract disuse.     

Complete amino acid sequence of goose VLDV-neurophysin Traces of a putative gene conversion between promesotocin and provasotocin genes

Goose VLDV-neurophysin (mesotocin-associated neurophysin) has been purified from posterior pituitary glands through molecular sieving on Sephadex G-75 and high-pressure reverse-phase liquid chromatography on Nucleosil C-18 columns. Despite apparent molecular mass of unreduced VLDV-neurophysin measured by polyacrylamide gel electrophoresis with sodium dodecylsulfate appeared near 17kDa, this value fell to 11 kDa after reduction with mercaptoethanol, suggesting the existence of a homodimer. Complete amino acid sequence (93 residues) of goose VLDV-neurophysin has been determined. N- and C-terminal sequences of the protein have been established by Edman degradation (microsequencing) and use of carboxypeptidase Y, respectively. Peptides derived from oxidized or carboxamidomethylated neurophysin by trypsin or staphylococcal proteinase hydrolyses have been isolated by high-pressure liquid chromatography and microsequenced, allowing determination of the complete sequence. Comparison within the vertebrate VLDV-neurophysin lineage, namely goose VLDV-neurophysin to mammalian VLDV-neurophysins and to deduced toad VLDV-neurophysin, reveals a residue insertion between positions 66 and 67 in the nonmammalian VLDV-neurophysins. When goose MSEL-neurophysin (vasotocin-associated neurophysin) and goose VLDV-neurophysin are compared to their bovine counterparts, identical substitutions are found in positions 17 (Asn in both goose neurophysins instead of Gly in both ox neurophysins), 18 (Arg instead of Lys), 35 (Tyr instead of Phe), and 41 (Thr instead of Ala). Identity of the sequences 10-74 in both ox neurophysins has been explained by partial gene conversion between oxytocin and vasopressin genes, and identical substitutions in both goose neurophysins might reveal a similar gene conversion between mesotocin and vasopressin genes in birds.     

Superior vena caval placement of a Kimray-Greenfield filter

Kimray-Greenfield filters placed in the inferior vena cava have been shown effective for prophylaxis against pulmonary embolism from lower extremity or pelvic thrombi. Percutaneous filter placement in the superior vena cava is described in a patient with pulmonary embolism and upper extremity thrombosis in whom anticoagulative therapy was contraindicated.