Assessment of "look-alike" packaging designs related to medication errors using information technology.

This study aimed to assess the similarity among press-through pack (PTP) sheets of pharmaceutical products in Japan. The appearance of PTPs was assessed using a pharmaceutical design database (PDD) of 2,750 pharmaceutical tablets comprising approximately 40 % of the 6,840 products marketed in Japan. Package sheet color (Sc), tablet color (Tc), character color (Cc), sheet line color (SLc), and upper color (Uc) were used to evaluate the uniformity of PTP sheet design. To assess the risk of misidentification, 1,000 prescriptions for 82,273 cancer patients were retrieved from 21,026,742 records in the claims database of the Japan Medical Data Center Co. Ltd., Tokyo, Japan. The most frequent PTP sheet colors for 143 drugs were Sc (silver), Tc (white), Cc (blue), SLc (none), and Uc (silver). The prescribing pattern of 1000 randomly chosen prescriptions was analyzed. Database records of prescriptions without tablets (n = 69), including only one PTP tablet (n = 292), and those with lack of PDD prescription data (n = 388) were excluded. Eventually, 236 prescriptions were evaluated. Fourteen prescriptions (5.9%) had PTP sheets with five matching elements and 29 had with four matching elements (12.3%). This novel PDD database for information technology concept easily identified similar PTP sheets involved in prescriptions dispensed in 18 % of evaluated cancer patients. The concept seems to be applicable for preventing look-alike dispensing errors.

[Development of an inspection-supporting system using drug images for unit dose packages].

When inspecting unit-dose packaged drugs, there would be some possibility of inspection errors and ultimately dispensing errors due to pharmacist's incorrect memory of drug identification. Therefore, this study was aimed to establish a computer-aided system for inspecting drugs of unit dose packages more accurately and efficiently. First, we analyzed the identifiability of 5846 tablets and capsules using drug codes, in order to define an identification problem for unit dose-packaged drugs. It was shown that as much as 36% of the drugs do not have any codes, 4.0% of the code-marked drugs have identical codes with others, and that 9.7% of the drugs with codes on both sides of the surface share the same code with other drugs. Thus, it was clearly shown that in many cases it is impossible to identify pharmaceuticals exactly using drug codes only. On the other hand, it was indicated that approximately 80% of the drugs which were not identified with drug codes only, could be identified when additional information on drugs' color, size, form, and splitting line was provided. Therefore, in this study, we designed an inspection-supporting system to present promptly all the information necessary for the drug identification by displaying real drug images as linked with prescribing information on the monitor. Retrieval of prescription data from the order entry host was automatically performed by entering patient's ID number or by selecting a patient from the name list of patients at the inspection terminal computer. Moreover, the system was equipped with abilities to automatically check drug interactions and duplicate prescriptions, to provide various information of prescribed drugs and to monitor patients' drug history. We used the developed system and evaluated that it is a useful tool for accurate and efficient inspection of unit dose-packaged drugs. In addition, the quality of drug inspection increased by utilizing system functions such as checking drug interactions and providing drug information.

Galectin-1 is a component of neurofilamentous lesions in sporadic and familial amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS), abnormal accumulation of neurofilaments induces pathological changes such as axonal spheroids, cord-like neurite swellings, and perikaryal conglomerate inclusions in degenerating motor neurons of the spinal cord, and the accumulation seems to cause motor neuron degeneration in this disease. Such ALS lesions were intensely labeled with HepSS-1, a monoclonal antibody to heparan sulfate. Since the identification of HepSS-1-immunoreactive substance seems to be an important step for understanding the molecular pathology of ALS, we purified the substance from human spinal cord tissue to homogeneity. Amino acid sequence of the protein was consistent with that of galectin-1. Immunohistochemistry using antibodies against recombinant human galectin-1 showed that galectin-1 was accumulated in these lesions in ALS. Although HepSS-1 was believed to be specific for heparan sulfate, it reacted with recombinant human galectin-1 which has no heparan sulfate moiety. The results show that galectin-1 is a component of the neurofilamentous lesions in ALS. Since galectin-1 has axonal regeneration-enhancing activity, the abnormal accumulation of galectin-1 to the lesions seems to be related to the pathological process of ALS.

[Development and evaluation of an individuals-oriented information-provision system for outpatients--utility of "drug Usage sheets" and "Drug Information Cards" for patient consultation].

We have implemented an information-provision system for outpatients at the department of pharmacy, University of Tokyo Hospital, in order to comply with the revised Pharmacists' Law by which pharmacists have been obliged to provide patients with information necessary for rational usage of medicine at the time they receive dispensed drugs. This system is linked on-line with the order entry system to print "Drug Usage Sheets" containing important drug information such as therapeutic effects and adverse reactions, as well as photographic color views of drugs. We prepared the sheets by extracting and classifying the original information, and by converting medical terms into lay expressions. Moreover, we developed "Drug Information Cards" to inform each patient of severe side effects and drug interactions, which should affect drug compliance, and implemented an individuals-oriented information system using both the "Drug Usage Sheets" and "Drug Information Cards." In this study, we evaluated the usefulness of this system from the viewpoint of patients' recognition and understanding on necessary drug information. It was indicated from questionnaires to patients that the "Drug Usage Sheets" help most patients understand the names, usage, effects, and general cautions including slight adverse reactions (i.e. grade 1), and that the use of colored letters for important parts and pictograms is a useful method to attract more attention from patients as compared with a conventional method using only letters. Most patients answered that the "Drug Usage Sheets" can be utilized in many ways and valuable in taking drugs with assurance. We formulated the "Drug Information Cards" by information processing: separation of early symptoms of adverse effects into subjective and objective ones and their classification into related organs. Moreover, the brand names of drugs which may cause drug interactions have been listed on the cards so that worsening of adverse reactions and drug interactions can be avoided. Although 14% of the patients answered that they became unsecured when informed on side effects, the percentage of such patients was significantly higher with those who received caution-required drugs for the first time or who have experienced drug side effects before, suggesting the need for combining oral explanation based on each patient's background and understanding on drug adverse effects. In conclusion, an efficient provision of drug information became possible through our integration of necessary drug information in this study, and the individuals-oriented system of drug information was established, which was demonstrated to contribute to the rational usage of medicine.

Role of xanthine oxidase in delayed lipid peroxidation in rat liver induced by acute exhausting exercise.

The aim of this study was to examine whether xanthine oxidase (XOD)-derived hepatic oxidative damage occurs in the main not during but following strenuous exercise. The degree of damage to hepatic tissue catalyzed by XOD was investigated immediately and 3 h after a single bout of exhausting exercise, in allopurinol and saline injected female Wistar rats. Allopurinol treatment resulted in increased hypoxanthine and decreased uric acid contents in the liver compared with the saline treated group, immediately and 3 h after the exercise. Analysis immediately after the exercise showed no changes in hepatic hypoxanthine, uric acid, and thiobarbituric acid-reactive substance (TBARS) contents in the saline treated group, when compared with the resting controls. However, significant increases in uric acid contents in the saline treated livers were observed 3 h after the exercise, relative to the controls. Hepatic TBARS content in the saline treated group were markedly greater than those in both the control and allopurinol treated groups after 3 h of recovery following the exercise. It was concluded that a single bout of exhausting exercise may impose XOD-derived hepatic oxidative damage, primarily during the recovery phase after acute severe exercise.

Increased epinephrine-induced cAMP response in severely diabetic BB/W rat liver.

The effect of prolonged diabetes on epinephrine-induced adenosine 3',5'-monophosphate (cAMP) response in the liver was examined in diabetes-prone BB/W rats. Basal and 1 microM epinephrine-induced cAMP release from isolated perfused liver was similar in non-diabetic and diabetic BB/W rats with preserved adipose tissue. In adipose tissue-absent diabetic rats losing intra- and retro-peritoneal adipose tissue completely, both basal and 1 microM epinephrine-induced cAMP release from the liver were enhanced (P<0.01, each case). Plasma epinephrine and norepinephrine were similar in non-diabetic, adipose tissue-preserved and -absent diabetic BB/W rats. The plasma free thyroxine level was similar in non-diabetic and adipose tissue-preserved diabetic BB/W rats, but was lower in adipose tissue-absent diabetic BB/W rats than in non-diabetic rats (P<0.01), but the frequency of lymphocytic thyroiditis was similar in these three groups, although plasma corticosterone was lower in adipose tissue-preserved diabetic BB/W rats (P<0.05) and the lowest in adipose tissue-absent diabetic BB/W rats (P<0.01). Lymphocytic infiltration was not observed in the adrenal or pituitary glands in any group. Plasma total protein and albumin were low in adipose tissue-absent diabetic BB/W rats (P<0.01, each case). In adipose tissue-absent diabetic BB/W rats, liver dysfunction and hepatomegaly, but no apparent histological change in the liver, were observed. Plasma glucose was higher (P<0.01) and plasma insulin lower (P<0.05) in adipose tissue-absent diabetic BB/W rats than in adipose tissue-preserved diabetic BB/W rats. In conclusion, epinephrine-induced cAMP response in the liver was enhanced only in adipose tissue-absent diabetic BB/W rats. Denervation supersensitivity was not likely to be responsible for the enhanced beta-adrenergic response. The observed reductions in plasma thyroxine and corticosterone seemed to result from severe diabetes. Although the severity of diabetes can vary continuously, severe diabetes with loss of adipose tissue appeared to cause significant changes in the metabolism and enhanced beta-adrenergic response in the liver.

The effect of food on the interaction of ofloxacin with sucralfate in healthy volunteers.

We have studied the effect of food on the interaction of ofloxacin with sucralfate. Six healthy men took a single oral dose of ofloxacin (200 mg) on 4 occasions: alone after overnight fasting or after breakfast (non-fasting), and with sucralfate fasting or non-fasting. There were no significant differences in the plasma concentration-time profiles of ofloxacin after ofloxacin alone between fasting and non-fasting conditions. On the other hand, the peak plasma concentration and AUC of ofloxacin after co-administration with sucralfate while fasting fell by 70 and 61% compared with ofloxacin alone; the changes non-fasting were 39 and 31% respectively. The interaction of ofloxacin with sucralfate was markedly reduced by food, but still could not be disregarded.

Calcitonin gene-related peptide immunoreactivity in familial amyotrophic lateral sclerosis.

The lumbar cords from 3 cases of familial amyotrophic lateral sclerosis (fALS), one case of vincristine neuropathy, and two control cases were examined with an antiserum to calcitonin gene-related peptide (CGRP). The anti-CGRP intensely labelled the spinal posterior horns in all cases. In the anterior horns, several perikarya and cord-like neuritic swellings, mostly axons, were labelled with the antibody in the fALS cases, whereas CGRP-positive structures were extremely rare in the cases other than fALS. It is possible that the accumulation of CGRP in the proximal axonal swellings and perikarya may result from entrapment of CGRP during the anterograde axonal transport, causing loss of, or decrease in, CGRP at the neuromuscular junction and producing weakness and atrophy of the muscles.

A determination of the positions of disulphide bonds in Paim I, alpha-amylase inhibitor from Streptomyces corchorushii, using fast atom bombardment mass spectrometry.

Paim I, a protein alpha-amylase inhibitor, is a single-chain polypeptide which consists of 73 amino acids, including 4 half-cystine residues. The positions of disulphide bonds in Paim I have been determined with the combination of enzymatic digestion and fast atom bombardment (FAB) mass spectrometry. Denatured Paim I was digested to peptides with Staphylococcus aureus V8 protease. These peptides were subjected to FAB mass spectrometry, with or without isolation by high-performance liquid chromatography. The positions of disulphide bonds in Paim I were determined from the relative molecular masses of the peptides containing a disulphide bond and by the enzyme specificity of S. aureus V8 protease. It is deduced that Paim I has two disulphide bridges at Cys(8)--Cys(24) and Cys(42)--Cys(70).

Serum total and HDL cholesterols according to reproductive status in Japanese females.

In order to observe variations according to reproductive status, serum total cholesterol (TC) and HDL cholesterol (HDL-C) were investigated in 153 pregnant, in 153 age-adjusted non-pregnant females, in 787 females aged 45-54 years living in a northern suburb of Tokyo, and in 150 12-year-old girls from a private junior high school in a southern suburb of Tokyo. Non-menstruating (non-menarcheal, postmenopausal) females had significantly higher TC and significantly lower HDL-C/TC than menstruating (menarcheal, premenopausal) females did in both the age groups of 12 and 45-54 years, although no significant difference of HDL-C was found between them. The menstruating females tended to be more overweight in Quetelet's index and had thicker skinfolds. Pregnant females at the eighth month of gestation revealed a significantly high value of both TC and HDL-C vs age-adjusted non-pregnant females, while at the fourth month of gestation only HDL-C was high.

Congenital heart disease in high school and college students.

The prevalence and relative frequency of congenital heart disease in high school and college students were investigated during the period April 1970-March 1976. Forty congenital lesions were found among 13,127 subjects which shows a rate of 3 per thousand. The ratio of congenital lesion to rheumatic heart disease was 4/1. Ventricular septal defect was the most common defect, found in 30% of all lesions followed by atrial septal defect (20%) and patent ductus arteriosus (17.5%). The prevalence and relative frequency in those investigated differed only slightly from the results obtained among children. The possibility of spontaneous closure of ventricular septal defect during adulthood strongly suggested itself when compared with our previous data on post middle age subjects.