One hundred twenty-nine dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the new dihydroxyquinone derivative of anthracene, ...mitoxantrone, which was administered IV at 21-day intervals at dosages ranging from 2.5 to 5 mg/m2 body surface area. Each dog was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the dog died, whichever came first. The number of dogs in each evaluation period were as follows: 1 dose (n = 129), 2 doses (n = 82), 3 doses (n = 43), 4 doses (n = 26), 5 doses (n = 19), 6 doses (n = 9), 7 doses (n = 6), 8 doses (n = 5), 9 doses (n = 3), and 10 doses (n = 1). The most common signs of toxicosis were vomiting, diarrhea, anorexia, and sepsis secondary to myelosuppression. None of the dogs died of complications resulting from mitoxantrone treatment. Dogs with signs of toxicosis during the 21-day interval from administration of the first dose of mitoxantrone were 95 times (P = 0.003) more likely to develop signs of toxicosis during the 21-day interval from the second dose of mitoxantrone. Similarly, dogs that developed signs of toxicosis during the 21-day interval from the administration of the second dose were 34 times (P less than 0.001) more likely to develop signs of toxicosis during the 21-day interval from the administration of the third dose. With each 1 mg/m2 increase in mitoxantrone, the odds of developing signs of toxicosis increased by 5.9 fold (P less than 0.001).
This paper concerns a dispute at the Adelaide Hospital in September 1896 between Professor Archibald Watson, Pathologist, Honorary Consulting Surgeon and sole remaining University teacher at the ...hospital, and Alexander Disney Leith Napier, who had arrived from England to fill the place of the honorary surgeons who had resigned from the hospital. Watson accused Napier of incompetence in his management of 'Mrs L.', who died after a femoral hernia operation. Mrs L had a form of internal hernia causing intestinal obstruction, whereas all the medical attendants, including Watson, originally thought an old femoral hernia was the cause of her illness. By fortuitous coincidence the operation on the femoral hernia could have cured the internal hernia if the band of omentum attached to the femoral hernia had been divided. Watson became aware of the band at the post-mortem and then asserted that the operation should have taken it into account. Napier complained to the Board of the Hospital, alleging that Watson had misrepresented the facts when he conducted the post-mortem on the patient and that he was disloyal to the hospital. The Board found the complaint proved and invited Watson to resign; he declined and was dismissed. Undaunted, Watson circulated a privately printed pamphlet (entitled 'Mrs L.'s case'), which re-stated the events of the case and graphically described his post-mortem findings. It was submitted to the Chairman of a Select Committee of the Legislative Council of South Australia established to review the running of the hospital. The Committee recommended the setting up of a Royal Commission but the Government let the matter lapse.
Fifteen dogs were given doxorubicin, IV, at a dosage of 30 mg/m(2) of body surface. A commercially available biological extract of Serratia marcescens (BESM) was administered sc to 9 of these dogs ...(0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of BESM to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of BESM SC: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (G-CSF) by enzyme immunoassay. Increasing the dosage and schedule of administration of BESM reduced the duration and severity of doxorubicininduced myelosuppression. Neutrophil counts of the group of dogs given BESM daily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P 0.05) above pretreatment values in BESM-treated dogs after day 7. Median neutrophil counts of the BESM-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12). The median counts decreased below normal ( 3,000 cells/microl) for 1 day in the dogs given BESM and doxorubicin, and for 3 days in the dogs that were given only doxorubicin. Four of the 6 dogs not treated with BESM and none of those given BESM developed serious neutropenia ( 1,500/microl). There was an increase in canine G-CSF 4 to 6 hours after BESM was administered to dogs at dosages of 0.16 and 0.32 mg/kg. These findings demonstrate that BESM is capable of reducing the duration and severity of doxorubincin-induced myelosuppression, and that this may be at least partially mediated by G-CSF
Interleukins are biologically active glycoproteins derived primarily from activated lymphocytes and macrophages. Tremendous insight into the biochemical and biological properties of interleukins has ...been gained with advances in recombinant DNA technology, protein purification, and cell‐culture techniques. The biological properties of interleukins include induction of T‐lymphocyte activation and proliferation, augmentation of neutrophil, macrophage, and T‐lymphocyte cytotoxicity, and promotion of B lymphocyte and multilineage bone marrow stem‐cell precursor growth and differentiation. Interleukins may play a role in the pathogenesis of several important diseases. Interleukin therapy is likely to play an important role in the treatment of cancer, infectious diseases, and immunodeficiency syndromes.
Background: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with ...amputation and doxorubicin chemotherapy.
Hypothesis: Survival will be prolonged in dogs receiving BAY 12–9566.
Animals: The study included 303 dogs with appendicular osteosarcoma.
Methods: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12–9566; 4‐4–4‐(chlorophenyl)phenyl‐4‐oxo‐2S‐(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy.
Results: Median survival for all 303 dogs was 8 months; and 1‐year, 2‐year, and 3‐year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12–9566 did not influence survival. Multivariate analysis revealed that increasing age (P= .004), increasing weight (P= .006), high serum alkaline phosphatase (ALP) (P= .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P= .013), and as plasma active MMP‐2 concentrations increased (P= .027), the risk of dying increased.
Conclusions and Clinical Importance: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.
In a previous study we described a problem-based criterion-referenced test of the clinical competence of medical students which was felt to offer advantages over the traditional final-year ...examination. This paper reports the validity and reliability studies on which it is possible to judge the value of this new test when compared to the traditional approach. The results demonstrate a high level of content validity and provide evidence of the construct validity of the test. Efforts to obtain measures of concurrent and predictive validity were thwarted by a failure to attain reliable assessments of ward performance from resident and consultant staff. Satisfactory levels of internal consistency were established for the whole test. Marker reliability was satisfactory in all sections of the test except for those requiring examiners to rate practical clinical skills. This was so despite the use of simulated patients, behavioural check-lists and rater training. Possible solutions to this problem are discussed. It is concluded that this new approach overcomes many of the measurement problems inherent in the traditional final examination. It has been shown to be feasible to construct and administer in the medical school setting without the need for the allocation of additional resources.
This paper reports a study which compared the performance of different groups of students and doctors on identical and equivalent tests set in an objective-type format and in a free-response format. ...The tests were designed to ensure that the content was relevant to clinical practice at the hospital intern level. In all test situations candidates' scores were significantly higher in the objective tests than in the free-response tests. This difference was greater for the more junior and less competent students than for the more competent doctors. The cueing effect of the options was thought to be the main factor responsible for the difference in performance. The results of a questionnaire survey demonstrated that students were aware of the deficiencies in multiple-choice tests. A large majority of the students believed that the free-response tests gave a more accurate assessment of their clinical ability. It was found that in these tests, aimed at measuring aspects of clinical competence, multiple-choice questions appeared to overestimate the candidate's ability to an extent that made them less suitable than free-response questions for this purpose. It was also found that free-response tests, of the type used in this study, provide a suitable alternative to multiple-choice tests for use in the written section of clinical examinations. It was concluded that the written component of the final examination in the medical course should have a preponderance of free-response items over multiple-choice items.
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