Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR).

Oral transmucosal fentanyl citrate (OTFC); Actiq) is a drug delivery formulation used for management of breakthrough cancer pain. Previous studies with open-label comparisons indicated OTFC was more effective than patients' usual opioid for breakthrough pain. The objective of this study was to compare OTFC and morphine sulfate immediate release (MSIR) for management of breakthrough pain in patients receiving a fixed scheduled opioid regimen. This double-blind, double-dummy, randomized, multiple crossover study was conducted at 19 US university- and community-based hospitals and clinics and comprised 134 adult ambulatory cancer patients. Patients were receiving a fixed scheduled opioid regimen equivalent to 60-1000 mg/day oral morphine or 50-300 microg/h transdermal fentanyl, were using a 'successful' MSIR dose (15-60 mg) as defined by entry criteria, and were experiencing 1-4 episodes of breakthrough pain per day. In open-label fashion, OTFC was titrated such that a single unit (200-1600 microg) provided adequate pain relief with acceptable side effects. Successfully titrated patients entered the double-blind phase of the study and received ten prenumbered sets of randomized capsules and oral transmucosal units. Five sets were the successful OTFC dose paired with placebo capsules, and five sets were placebo OTFC paired with capsules containing the successful MSIR dose. Patients took one set of study medication for each episode of target breakthrough pain. Pain intensity (PI), pain relief (PR) and global performance of medication (GP) scores were recorded. Pain intensity differences (PID) were calculated and 15-min PID was the primary efficacy variable. Adverse events were recorded. Sixty-nine percent of patients (93/134) found a successful dose of OTFC. OTFC yielded outcomes (PI, PID, and PR) at all time points that were significantly better than MSIR. GP also favored OTFC and more patients opted to continue with OTFC than MSIR following the study. Somnolence, nausea, constipation, and dizziness were the most common drug-associated side effects. In conclusion, OTFC was more effective than MSIR in treating breakthrough cancer pain.

Desmopressin-induced improvement in bleeding times in chronic renal failure patients correlates with platelet serotonin uptake and ATP release.

Hemostatic defects resulting in life-threatening hemorrhagic episodes are a common occurrence in the chronic renal failure patient. Hemorrhagic tendencies correlate best with laboratory tests of bleeding times. The identification of a specific hemostatic defect and its role in bleeding dyscrasias has yet to be elucidated. Our studies demonstrate that factor VIII coagulant activity and factor VIII related antigen (vWF:Ag) are normal or greatly elevated in uremic renal failure patients with greatly prolonged bleeding times. The multimeric state of the von Willebrand factor is also normal in these patients. The bleeding times were normalized in all 15 patients, 90 minutes post-infusion with desmopressin (DDAVP). No significant changes in factor VIII/vWF associated properties, blood cell counts, or coagulation factors were observed post-DDAVP treatment. However, a significant increase in platelet serotonin uptake (p less than .025) and ATP release (p less than .025) was detected after DDAVP treatment. These results indicate that DDAVP acts on the platelet membrane. This is further substantiated by the ability of DDAVP to block vasopressin-induced platelet aggregation in a dose- and time-dependent fashion. Perturbations in the movement and storage of serotonin and the release of adenosine 5'-triphosphate (ATP) in the platelets of uremic individuals are proposed to play a critical role in regulating bleeding times.

Probable hypersensitivity vasculitis in a dog.

Allergy immunotherapy (hyposensitization) injections or ibuprofen were implicated as causes of hypersensitivity vasculitis in a dog suffering from probable food allergy. The vasculitis was associated with increased complement component, C3, and resulted in deep, ulcerated draining nodules and plaques on the forelimbs, lateral aspects of the thorax, and thighs. Injections had been given as immunotherapy for suspected atopy. Vasculitis, associated with allergy immunotherapy and increased complement component, C3, as well as with nonsteroidal anti-inflammatory drugs, has been reported in human beings.

Chylothorax associated with blastomycosis in a dog.

Respiratory distress caused by pleural effusion resulted from chylothorax. Thoracic drainage and lowfat dietary therapy was effective in removing and preventing significant recurrence of the chylothorax; however, the patient died unexpectedly. At necropsy a blastomycotic granuloma found at the precava was considered the cause of the chylothorax. There had been no recognizable antemortem signs of blastomycosis. Blastomycosis can be considered as a rare cause of chylothorax.

Demographic change and population policy in four Asian nations: Japan, Korea, Singapore and Thailand.

PIP: The author examines differences among the recent population histories and population policy approaches of Japan, the Republic of Korea, Singapore, and Thailand. Particular attention is paid to the experience of Thailand and to the applicability of that country's experience to Indonesia. The author suggests that although the fertility decline was primarily linked to socioeconomic development in the other three countries considered, in Thailand it has been due to other factors such as the national family planning program.^ieng

Sunlight-skin cancer association in the dog: a report of three cases.

Squamous cell carcinoma is one of the most frequently recognized neoplastic diseases of the canine integument, although few risk factors influencing tumor development have been clearly defined. Three dogs with cutaneous squamous cell carcinomas are reported. Tumors developed in lightly-pigmented, glabrous following chronic sunlight exposure and long period of dermatosis. Microscopic examination of tissues from the three dogs showed progressive development of epithelial hyperplasia through stages of solar keratosis-like lesions to invasive and metastatic squamous cell carcinoma.

Experimental swine vesicular disease, pathology and immunofluorescence studies.

Two day old piglets were inoculated intravenously with 1 ml of swine vesicular disease virus UK-G 27-72 isolate. Using infectivity tests, immunofluorescent staining and gross and histopathological examination, pathogenesis of the infection was studied in tissue specimens collected daily from one through seven days postinoculation. Swine vesicular disease virus had a strong affinity for the epithelia of the tongue, snout, coronary band and lips, the myocardium and the lymphoid elements of the tonsil and the brain stem. The virus had the greatest affinity for the epithelium of the tongue. However, there was no evidence that the tongue was the initial replication site for swine vesicular disease virus. Prickle cells in the stratum spinosum appear to be the primary targets for the virus. The necrotic foci in the stratum spinosum appeared first, followed the next day by reticular degeneration and multilocular intraepidermal vesicular formation. In the digestive tract and most of the other visceral organs the short duration and sudden drop of the virus titres and the negative fluorescence and pathological findings suggest that these are not important sites for the replication of swine vesicular disease virus in this experiment. The virus was recovered from most of the central nervous tissue specimens. Although the piglets had significant central nervous system lesions, signs of impaired central nervous system function were not detected. However, subtle nervous signs could have been obscured by difficulties in locomotion resulting from severe lesions of the feet.