Histological changes following high-dose methotrexate and cisplatinum administration and the influence of dosage scheduling

Histological changes were studied in experimental animals following the intraperitoneal administration of high-dose cisplatin with or without high-dose methotrexate and citrovorum factor. There were pronounced renal toxicities with high-dose (10 mg/kg) cisplatin, particularly involving distal tubules with glomerular congestion. However, lower toxicities were noted with reduced dosage of cisplatin (5 mg/kg) and especially if given once as a single bolus injection instead of a 5-day regimen. Renal and hepatic toxicities were marked with concomitant methotrexate administration leading to hemorrhagic diathesis and shorter survival. However, toxicities were relatively reduced when cisplatin was given as a single bolus injection instead of a 5-day divided course. Such information may prove helpful in future planning of combination chemotherapy in patients with malignancies using these two agents.     

Adenosine receptor-mediated relaxation in coronary artery: evidence for a guanyl nucleotide-binding regulatory protein involvement

The involvement of a guanine-nucleotide-binding regulatory protein (G protein) in the relaxing responses to adenosine receptor agonists was investigated in bovine coronary vessels. Ring segments of left anterior descending artery branches were suspended in organ baths for measurement of isometric tension. The adenosine analogs, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) caused concentration-dependent relaxations of coronary rings contracted with KCl. The relaxing effects of NECA and CAD were antagonized by the adenosine receptor antagonist 8-phenyltheophylline indicating the involvement of an adenosine receptor. In a separate series of experiments, incubation with cholera toxin inhibited the relaxing responses to NECA, CAD and isoproterenol but not those produced by sodium nitroprusside. Treatment with forskolin did not reduce the relaxing responses to NECA or CAD. N-ethylmaleimide and NaF/AlCl3 caused significant inhibition of the relaxations produced by both NECA and CAD. Incubation with pertussis toxin was without effect on relaxations induced by NECA and CAD. These results provide evidence for the involvement of G protein (possibly stimulatory G proteins) in the relaxing effects mediated by the bovine coronary artery adenosine receptor.     

Renal,cardiac, and systemic hemodynamic effects of the dopamine receptor agonist SK&F 85174 in anesthetized dogs

SK&F 85174 is a mixed DA-1/DA-2 receptor agonist which is shown to inhibit sympathetic neurotransmission and cause hypotension in anesthetized animals. In this study, we have determined the regional and systemic hemodynamic effects of an intravenous infusion of SK&F 85174 (5 μg/kg/min for 5 min) in pentobarbital-anesthetized dogs and attempted to identify the dopamine receptor subtype(s) involved in the cardiac as well as vascular effects of this compound. SK&F 85174 produced significant decreases in mean blood pressure (MBP), left ventricular pressure (LVP), left ventricular dp/dt, total peripheral resistance (TPR) and renal vascular resistance (RVR), and a significant increase in renal blood flow (RBF). There were no significant changes in heart rate, cardiac output, coronary blood flow, or coronary vascular resistance. Prior treatment with SCH 23390 (DA-1 receptor antagonist) significantly attenuated the effects of SK&F 85174 on MBP, LVP, TPR, RBF, and RVR. In a second group of dogs S-sulpiride (DA-2 receptor antagonist) significantly antagonized the effects of SK&F 85174 on MBP, LVP, and dp/dt, but did not influence its effects on RBF, TPR, and RVR. These results show that (a) a decrease in total peripheral resistance and not the cardiac output accounts for the hypotensive action of SK&F 85174, (b) the renal hemodynamic effects of SK&F 85174 are mediated primarily via the activation of DA-1 receptors, and (c) whereas DA-1 receptors are involved primarily with the hypotensive action of this compound, it appears that activation of DA-2 receptors also contributes to the hypotension.     

Transcutaneous electrical nerve stimulation for pain management in patients with uncomplicated minor rib fractures.

OBJECTIVE: Few non-surgical conditions are more painful than rib fractures. There are a few methods for pain relief in patients with minor rib fractures. METHODS: We used a non-steroidal anti-inflammatory drug (NSAID, Naproxen sodium) and transcutaneous electrical nerve stimulator (TENS) to control pain of the patients with uncomplicated minor rib fractures. One hundred consecutive patients admitted to Kartal Education and Research Hospital Emergency Service, were randomized into four groups. The patients were assigned to one of the following pain treatments: NSAID, TENS, NSAID plus inactive TENS or placebo. The patients used NSAIDs and placebo four times a day and TENS twice a day for 3 days. All patients were asked to assess their pain level with a scoring system on days 0, 1 and 3. RESULTS: The most effective treatment was TENS on days 1 and 3 (P<0.05). Although NSAID and NSAID plus inactive TENS controlled pain better than placebo on day 1 (P<0.05), this superiority did not continue to day 3 (P>0.05). There was no difference between NSAID and NSAID plus inactive TENS in controlling pain on either days 1 or 3. CONCLUSION: We conclude that TENS was more effective than NSAID or placebo in patients with uncomplicated minor rib fractures, because of its prominent and admirable efficacy in reduction of pain.     

Wilms' tumor of the ovary: A case report

The occurrence of true extrarenal Wilms' tumor is extremely rare. The most frequently noted extrarenal sites are the retroperitoneal and inguinal regions. In the female genital tract, the occurrence of Wilms' tumor has been documented in the uterus, endocervix, and ovary in isolated case reports. In this article the authors describe a case of ovarian Wilms' tumor in a 3.5-year-old girl. Her abdominal ultrasound scan and computed tomography scan showed a solid mass with cystic components on the left lower quadrant. Total excision was performed with left salpingo-oophorectomy. There was no other mass and also no evidence of metastasis. To the best of the authors' knowledge, this patient is the first reported case of primary ovarian Wilms' tumor arising in childhood.     

Ginger (Zingiber officinale) and rheumatic disorders

Oxygenation of arachidonic acid is increased in inflamed tissues. In this condition products of two enzymic pathways--the cyclooxygenase and the 5-lipoxygenase producing respectively prostaglandins and leukotrienes--are elevated. Of the cyclooxygenase products, PGE2 and of the lipoxygenase products, LTB4 are the strongest candidates for mediating inflammation. Non-steroidal anti-inflammatory drugs which inhibit the cyclooxygenase, and corticosteroids are used to treat such disorders. Both types of drugs produce adverse side-effects on prolonged use. Ginger is reported in Ayurvedic and Tibb systems of medicine to be useful in rheumatic disorders. Seven patients suffering from such disorders reported relief in pain and associated symptoms on ginger administration.     

Dynein–dynactin complex subunits are differentially localized in brain and spinal cord, with selective involvement in pathological features of neurodegenerative disease

Aims: The dynein–dynactin complex, mostly recognized for axonal retrograde transport in neurones, has an ever growing list of essential subcellular functions. Here, the distribution of complex subunits in human central nervous system (CNS) has been assessed using immunohistochemistry in order to test the hypothesis that this may be altered in neurodegenerative disease. Methods: Three dynactin and two dynein subunits were immunolocalized in the CNS of human post mortem sections from motor neurone disease, Alzheimer's disease and patients with no neurological disease. Results: Unexpectedly, coordinated distribution of complex subunits was not evident, even in normal tissues. Complex subunits were differentially localized in brain and spinal cord, and localization of certain subunits, but not others, occurred in pathological structures of motor neurone and Alzheimer's diseases. Conclusions: These results suggest that dynein–dynactin complex subunits may have specific subcellular roles, and primary events that disturb the function of individual components may result in disequilibrium of subunit pools, with the possibility that availability for normal cytoplasmic functions becomes impaired, with consequent organelle and axonal transport misfunction.     

Albendazole is Not Effective for Primary Treatment of Hepatic Hydatid Cysts

Introduction In current practice, minimal invazive interventions such as percutaneous drainage and laparoscopic surgery in adjunct treatment with benzimidazoles have been gaining acceptance in treatment of hydatid cystic disease with minimal morbidity and mortality. In this prospective study, the efficacy and validity of primary medical therapy in the treatment of hydatid cystic disease has been investigated. Patients and methods Sixty-five patients with hepatic cystic disease were treated with albendazole alone between January 2004 and June 2007. All of the patients were administrated albendazole as 10 mg kg⁻¹ day⁻¹ divided into two equal doses for 6 months with ultrasonography (USG), serological tests, full-blood cell count and hepatic function tests performed in 2 months intervals in the course of treatment. Results Fifty of the patients were female and 15 were male with a mean age of 47.0 ± 16.9 (17–80). A total number of 106 cysts were present in 65 patients. Mean cystic diameter was 5.5 ± 3.6 (1–16). In 41 of the patients, cysts were solitary and in remaining 24 patients cysts were multiple. Mean follow-up period was 28.3 ± 8.6 (12–42) months. The overall success rate of albendazole therapy was 18 % (12/65) in the study. Conclusion Albendazole therapy for hepatic hydatidosis is not effective in the vast majority of patients and, therefore, should not be used as the primary therapy for patients who are surgical candidates.