Objective evaluation of generic drug information

Pharmacists active in health care venues need to be able to evaluate generic drugs in terms of effectiveness, safety, and economy to ensure that they are used appropriately. As part of the ongoing study of these factors, we carried out an objective evaluation of information provided for generics. A minimum of 20 commercially available products was considered for each pharmaceutical ingredient. The information subjected to evaluation consisted of the text of drug package inserts and information noted on interview forms. Using our own criteria for evaluating drug information, we attempted to quantify the amounts of information provided. Then, based on the numerical values obtained, we calculated information quantities with reference to drug prices to study the relationship between prices and available information for original drugs and their later-developed, generic equivalents. A total of 14 different pharmaceutical ingredients (327 product items) were considered, with the information quantity for generics amounting to 27.9+/-17.8-46.3+/-21.4% (Mean+/-S.D.) that for the original drugs. Examined on the basis of individual pharmaceutical companies, the corresponding ratio came to 15.1+/-7.8-62.4+/-6.4% (Mean+/-S.D.). For generics, the relationship between drug price (expressed against a value of 1.0 for original drugs) and information quantity (Qua(i)) came to 0.79+/-0.46-1.90+/-0.79% (Mean+/-S.D.). These results clearly point to the importance of evaluating information quantity for generic drugs on a maker-by-maker basis.     

Long-term complete response of multiple hepatic metastases from carcinoma of the papilla of Vater using intrahepatic infusion of 5-FU with low-dose cisplatin following pancreaticoduodenectomy

Of all distant metastases from carcinoma of the papilla of Vater (CPV), the liver is the most frequent site (more than 60%) and should be specifically targeted in the effort to improve the prognosis. However, the optimal chemotherapy regimen for nonresectable liver metastasis has not been clearly established. In this preliminary report, we note a patient with multiple hepatic metastases from CPV successfully treated using intrahepatic infusion of 5-fluorouracil (FU) with low-dose cisplatin. A 62-year-old woman underwent curative pylorus-preserving pancreaticoduodenectomy for CPV. Four months after surgery, followup computed tomography (CT) demonstrated multiple liver metastases. Weekly intrahepatic arterial infusion chemotherapy of 5-FU, 350 mg/m², with low-dose cisplatin (7 mg/m²) was started. Ten months after starting chemotherapy, a complete response was obtained. To date, the patient continues to receive this weekly hepatic arterial infusion chemotherapy without any side effects, and she has successfully maintained a long-term complete response for 20 months. The patient remains well and was able to proceed with daily activity at the last follow up 30 months after starting this chemotherapy regimen. This regimen is safe and effective and is recommended as one of the treatment choices for liver metastases from CPV.     

Scleral indentation optimizes visualization of anterior chamber angle during goniosynechialysis

PURPOSE: To propose a new surgical technique for optimized visualization of the chamber angle using scleral indentation under an operating microscope in goniosynechialysis (GSL). PATIENTS AND METHODS: Six volunteers with normal chamber angle and five patients with synechial angle closure glaucoma were examined. Scleral indentation 2 mm posterior to the limbus was performed during observation of chamber angle. Width of trabecular meshwork in images was recorded through a CCD camera mounted on an operating microscope. Trabecular-iris angle and trabecular-corneal angle obtained by ultrasound biomicroscopy were used for the parameters for the angle configuration. GSL with scleral indentation was performed in the patients. RESULTS: According to the visibility of the chamber angle, width of trabecular meshwork in images significantly increased from 0.34 +/- 0.08 mm equivalent (mean +/- SD) to 0.67 +/- 0.14 mm equivalent (P = 0.0001) with scleral indentation. According to the angle configurations, trabecular-iris angle significantly increased from 39.6 +/- 3.8 degrees to 47.5 +/- 6.6 degrees (P = 0.0016), and trabecular-corneal angle significantly decreased from 169.8 +/- 5.5 degrees to 158.7 +/- 5.4 degrees (P < 0.0001). All patients were successfully treated with GSL using scleral indentation. CONCLUSION: Scleral indentation provided the surgeon an optimized visualization of the anterior chamber angle. Deepening of the chamber angle and steeping in trabecular-corneal curvature probably induced the plane of the trabecular meshwork less oblique to the surgeon's visual axis. This enhanced visualization promises the accuracy and safety of GSL.     

Generalized tetanus with intractable autonomic cardiovascular instability in an aged woman

Tetanus is characterized by tetanic convulsions related to the actions of tetanospasmin produced by Clostridium tetani. Another important characteristic of tetanus is the instability of the cardiovascular system related to sympathetic hyperactivity in the autonomic nervous system, and it may be an important prognostic factor. We report a patient with tetanus in whose unstable circulatory kinetics made circulation management difficult. A 77-year-old woman who injured in a fall, 11 days after trismus appeared and 3 day after convulsion appeared. It was not severe case in the acuity classification. However, repeated generalized convulsions and autonomic imbalance involving the cardiovascular system were observed clinically, suggesting a severe case. Because of the unstable circulatory kinetics, the patient was carefully managed was performed in the intensive care unit (ICU), and she improved. ICU management may be essential for treating severe tetanus with cardiovascular complications. Acquired immunity is not achieved after the onset of tetanus, and since elderly people, in particular, as in our own caset, are easily injured when they fall, we recommend vaccination.     

Human glioblastomas overexpress ADAMTS-5 that degrades brevican

Selective cleavage of the Glu³⁹⁵-Ser³⁹⁶ bond of brevican, one of the major proteoglycans in adult brain tissues, is thought to be important for glioma cell invasion. Our previous biochemical study demonstrated that ADAMTS-4, a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, has such an activity. In the present study, we examined brevican-degrading activities of ADAMTS-1, -4 and -5 at the cellular level, and their expression and localization in human glioma tissues. In 293T transfectants expressing ADAMTS-4 or ADAMTS-5, brevican was cleaved into two major fragments in an identical pattern, but no such degradation was observed with ADAMTS-1 transfectants. When the expression levels of these ADAMTS species were examined by real-time quantitative PCR, only ADAMTS-5 was found to be overexpressed in glioblastoma tissues compared to control normal brain tissues (P <0.05). In situ hybridization and immunohistochemistry demonstrated that ADAMTS-5 is expressed predominantly in glioblastoma cells. Forced expression of ADAMTS-5 in glioma cell lines stimulated cell invasion. These results demonstrate for the first time that ADAMTS-5 is capable of degrading brevican and is overexpressed in glioblastoma cells, and suggest that ADAMTS-5 may play a role in glioma cell invasion through the cleavage of brevican.     

Discovery of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent and selective human prostaglandin EP(4) receptor antagonists

Two novel classes of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent and selective EP(4) antagonists have been discovered. The optimized diphenyloxzole 8 and Ndelta-Z-ornithine 11 effectively competed with [(3)H]PGE(2) binding to human recombinant EP(4), with K(i) values of 0.30 nM and 0.91 nM, respectively, and were selective for all members of the human prostanoid receptor family. 8 was shown to exhibit good pharmacokinetic properties in rats and dogs and potent inhibitory activity toward in vitro PGE(2)-promoted IgE synthesis.     

New experimental model of crush injury of the hindlimbs in rats

BACKGROUND: Crush injury (CI) remains a life-threatening condition. Because there is a shortage of animal models of CI, we purposed to develop a reproducible model of CI of hindlimbs in rats and to evaluate correlation between the volume of muscles traumatized and the severity of CI. METHODS: The right or both hindlimbs of anesthetized rats were compressed for 6 hours under blocks weighing 3 kg. This was followed by 3 hours of reperfusion. Serum lactate, base excess (BE), and potassium (K) were measured at 10 minutes after cannulaton (baseline), immediately before release (compression), and 3 hours after release (reperfusion). Serum creatine phosphokinase (CK), lactate dehydrogenase (LDH), aspartate transferase (AST) and alanine transferase (ALT) were measured at baseline and reperfusion. Muscles and kidneys were evaluated morphologically. In a separate group of animals treated in the same way, survival rate was monitored for 168 hours. RESULTS: Unilateral CI did not induce serious systemic impairment. Bilateral CI resulted in severe lactic acidosis. Serum K levels increased similarly and significantly in both groups. Serum CK levels correlated strongly with the volume of muscles traumatized. Bilateral CI produced a sharp increase in serum LDH, AST and ALT levels by the end of experiment. Signs of direct cellular damage and ischemia-reperfusion injury were found in histology specimens. In bilaterally crushed rats there were patent signs of acute tubular necrosis at 24 hours after insult. All rats with unilateral CI survived, whereas mortality rate reached 58.3% in rats with bilateral CI. The majority of these animals died within 24 hours after compression. CONCLUSIONS: We developed a valid experimental model of severe CI of the hindlimbs in rats. Systemic responses to CI and the severity of CI appeared to correlate strongly with the volume of muscle traumatized.