[Molecular genetics of Alport syndrome]. Alport syndrome is a hereditary glomerulonephritis in which progressive loss of kidney function is often accompanied by sensorineural deafness. Ultrastructural studies in glomerular basement membranes (GBM) of Alport syndrome patients implicate an altered GBM protein structure as the cause of nephritis. The product of COL4A5, the alpha 5 (IV) collagen chain, is a specific component of GBM of the kidney. Various mutations in the COL4A5 gene have been identified in X-linked dominant Alport syndrome, and these aberrations of the alpha 5 (IV) can account for at least a part of X-linked Alport syndrome.


[TGF-beta gene expression in mesangial cells]. TGF-beta recently has been shown to inhibit mesangial cell growth and to stimulate mesangial matrix synthesis by mesangial cells. Cultured rat mesangial cells expressed 2.5 kb TGF-beta mRNA, and removal of fetal calf serum (FCS) for two days decreased the TGF-beta mRNA level, which was then stimulated by addition of 17% FCS and TPA, one of the phorbol esters, although it is also reported by others that the mRNA expression was stimulated by PDGF, EGF, or high glucose. Bioassay and immunoblot analysis showed that mesangial cells produce and secrete substantial amounts of TGF-beta but mostly in latent forms. Moreover, addition of anti-TGF-beta neutralizing antibodies augmented mesangial cell growth, indicating that the secreted TGF-beta exerts a growth-inhibitory action on themselves. Thus, TGF-beta may function as an autocrine factor in mesangial cells, and it is suggested that mesangial cells may play an important role in the pathogenesis of glomerulopathy.


[Role of TGF-beta in glomerular diseases]. Accumulation of extracellular matrix (ECM) is a major histological change in glomerular diseases that progress to chronic renal failure. Such accumulation can be mediated by increased production of molecular signal such as cytokines. Transforming growth factor beta 1 (TGF-beta 1) has a combined effect of enhancing the synthesis of ECM, while inhibiting the proteolytic degradation of newly formed matrix proteins. TG1-F beta 1 has stimulative effects on the production of ECM by cultured rat mesangial cells. In an experimental glomerulonephritis, there was a close association between elevated expression of the TGF-beta 1 mRNA and development of glomerulonephritis. Treatment of glomerulonephritic rats with antiserum directed to a synthetic peptide from mature TGF-beta 1 prevented the histological accumulation of ECM in glomeruli. These results suggest that TGF-beta 1 may participate in glomerular matrix expansion.


[Glomerular extracellular matrix in glomerulosclerosis by molecular biology]. Many renal diseases progress to end-stage renal failure with glomerulosclerosis, irrespective of the cause of the disease. Glomerulosclerosis is characterized by an accumulation of extracellular matrices (ECM) due to increased synthesis of the ECM and/or decreased degradation of the ECM. Sclerotic lesions represent an accumulation of normal constituents of the ECM, including type IV collagen, laminin, proteoglycans, as well as, abnormal constituents such as type I and III collagens. The cDNAs for various ECM constituents have been obtained and it has become possible to study the status of their synthesis, in the transcriptional level, in various glomerular diseases. Studies suggest that hemodynamic factors and growth factors, such as, TGF-beta and PDGF are responsible for the development of glomerulosclerosis. Inappropriate expression of intrinsic mesangial cell metalloproteinases and tissue inhibitors of metalloproteinases also lead to glomerulosclerosis.


[Polymorphism of immunoglobulin heavy chain switch region in IgA nephropathy]. We examined the relation between IgA hyperproduction and polymorphism of the immunoglobulin heavy chain switch (S) region in patients with IgA nephropathy. The frequency of the heterozygous phenotype of IgA2 switch region was significantly increased in these patients. The patients showed a significant increase in the amount of serum IgA, IgA bearing cells and levels of proteinuria. We also compared two reports on the S region in Europe, which showed different results, and found different frequencies in the phenotype of the S region. These findings suggest that IgAN patients in various countries show heterogeneity in the S region and that this polymorphism might be associated with IgA hyperproduction and the development of proteinuria in Japanese patients.


[Recent progress in molecular biology of inherited tubular transport abnormalities]. Recent progress in the molecular biological approach to analysis of inherited tubular transport abnormalities is reviewed. 1) cDNAs of several mammalian proteins, related to amino acid transport in renal tubular cell, have been cloned using an expression cloning in Xenopus oocytes. One of them stimulates the transport of cystine, dibasic amino acids and neutral amino acids and will accelerate the analysis of cystinuria. 2) Isolation of cDNAs, encoding human and rat vasopressin V2 receptors, has been reported. The deduced amino acid sequence seems to be a member of receptors with seven putative transmembrane regions. Analysis of this gene from patients with nephrogenic diabetes insipidus is in progress. 3) Analysis of carbonic anhydrase II (CA II) gene in a Belgian family with renal tubular acidosis associated with osteoporosis and cerebral calcification has shown a point mutation replacing an invariant histidine residue of CA II protein with tyrosine. 4) Oculocerebrorenal syndrome of Lowe (OCRL) is a X-linked disorder affecting the lens, brain and kidneys. The OCRL locus has been mapped to Xq24-26 by linkage analysis and by finding de novo X-autosome translocations at Xq24-26 in two unrelated females with OCRL. A cDNA has been isolated using yeast artificial chromosome and DNA inserts that span the X chromosome breakpoint from a female patient. Transcript for this cDNA is absent in unrelated male patients. The open reading frame encodes a new protein similar to human inositol-polyphosphate-5-phosphatase, raising a possibility that OCRL is an inborn error of inositol phosphate metabolism.


[Tumor suppressor genes associated with development of human renal cell carcinoma]. Several rodent studies based on molecular biology have suggested that accumulation of genetic alterations in cancer-associated genes is required to convert a normal cell into a malignant cell. Activation of oncogenes and inactivation of tumor suppressor genes appear to be involved in carcinogenesis. In renal cell carcinomas, we have recently implied that the presence of tumor suppressor genes at chromosome 3p13-14.3 and 21.3, the regions where are also commonly deleted in adenocarcinoma of the lung; at chromosome 5q21, the region where the MCC (mutated in colorectal cancer) gene and APC (adenomatous polyposis coli) gene are located; at chromosome 6q27; and at 10q 21-23. We have also indicated that genes on 3p is probably important for development of RCCs and genes on 5q, 6q, and 10q may be associated with progression of RCCs.


[Genotype and genetic diagnosis of APRT deficiency]. Adenine phosphoribosyltransferase (APRT) deficiency is one of the most common genetic diseases among the Japanese and is transmitted in an autosomal recessive manner. Urolithiasis is a typical symptom of this disease. Molecular analysis of the deficient APRT alleles revealed that 96% of disease-causing genes among the Japanese was accounted for only three alleles. Therefore, genetic diagnosis can be performed on most of the patients without determining the mutant sequence in each family. The ASO-PCR hybridization method differentiated all of these alleles. Linkage analysis using neighboring RFLP markers revealed that each of the three mutant APRT alleles had a common ancestral origin.


[Triplex DNA for therapeutics].

[Triplex DNA for therapeutics]. Application of triplex DNA, including therapeutic use for the genetic diseases, cancers and the diseases caused by viruses, such as AIDS is widely discussed today. The use of triplex DNA for the regulation of gene expression, especially at the transcriptional level, is discussed here by considering three criteria: (1) selection of target polypurine.polypyrimidine sequences, (2) designing triplex DNA to form, and (3) introduction of oligonucleotides into nuclei. This triplex DNA method can be used as an alternate to or in combination with the more popular method using antisense oligonucleotides, which regulates the gene expression at the posttranscriptional stage.


[Frequency of Helicobacter pylori in chronic gastritis with endoscopically defined erosion]. The frequency of Helicobacter pylori was histopathologically evaluated in biopsy specimens of the gastric mucosa from 112 patients which endoscopically diagnosed as erosion. The specimens, histopathologically diagnosed as chronic gastritis, were divided into eight groups according to age, sex and location. The Helicobacter pylori infection was revealed in 65% of all specimens observed, and the frequency in patients of their sixties was lower than that of the forties. The frequency in the elder was the lowest in the transitional zone of the gastric mucosa. These findings indicate that the decrease in the frequency of Helicobacter pylori begins in the transitional zone and subsequently in the antrum.


[Effect of ursodeoxycholic acid (UDCA) therapy for compensatory liver cirrhosis on liver function tests and serum bile acid metabolism]. Effect of ursodeoxycholic acid (600 mg/day 12 weeks) on liver function tests and bile acid metabolism were investigated in 6 patients with compensatory liver cirrhosis (CLC) and 6 with chronic active hepatitis (CAH). Serial determination of serum GOT, GPT and gamma-GTP after the initiation of UDCA revealed significant reduction in mean levels of these enzymes after 4 weeks, and further improvement was observed at the end of the 12-weeks treatment regimen (CLC: 79.3%, 81.1%, 51.5% of initial values, respectively, CAH: 61.2%, 59.3%, 42.8%). On the other hand, after UDCA administration, serum total bile acid increased and UDCA became the predominant bile acid in CLC and CAH patients. Other endogenous bile acids decreased in both groups, but reduction rate of serum chenodeoxycholic acid level in CLC was smaller than that in CAH group (CLC: 86.1% of initial values, respectively, CAH: 54.2%). During UDCA treatment, apparent side effect was not observed. We suggest that UDCA administration might constitute effective treatment for compensatory liver cirrhosis as well as chronic hepatitis.


[Evaluation of subjective happiness in the elderly using a visual analogue scale of happiness in correlation with depression scale]. A Visual analogue scale of happiness (VAS-H) was applied to elderly population in a community to evaluate their subjective quality of life. The study population consisted of 313 elderly people aged over 75. Using a 20 cm visual analogue scale (VAS), VAS-H was measured by asking subjects to place a single vertical mark on a horizontal line at a point corresponding to their current subjective degree of happiness judged from health condition and psycho-social background as a whole; The VAS-H was anchored on the left and with the words "-100%; unhappiest" and on the right end with the words "+100%; happiest". The scores of VAS-H (%) were obtained by multiplying the distance (cm) from the zero point to the vertical line by 10. To determine the characteristics of VAS from the standpoint of the quality of life, we compared VAS with scores of two kinds of established depression scale, because the mood which was assessed by these scale was supposed to be an important factor of the quality of life. The results of the simultaneously assessed Geriatric Depression Scale (GDS), and Zung's depression scale (SDS) which was obtained 1 year before for the same subjects were compared with that of VAS-H. The score of VAS-H had a significantly negative correlation with both GDS and SDS. In conclusion, VAS-H was a simple and useful method to evaluate degree of subjective happiness which was one factor of quality of life in the elderly people.


[Evaluation of subjective happiness in the elderly using a visual analogue scale of happiness to analyze the effect of life style and neurobehavioral function on subjective happiness]. The effects of activity of daily living (ADL), physical conditions, social environmental factors and neurobehavioral functions on subjective happiness were investigated in 313 elderly subjects. The degree of subjective happiness was measured using visual analogue scale of happiness (VAS-H). There was significant relationship between VAS-H and ADL. The VAS-H score had weak but significant correlation with physical conditions and neurobehavioral functions. The social environmental factors, especially economical conditions, family relationships and group behavior had a significant correlation with VAS-H. In conclusion, in apparent healthy elderly people, the subjective degree of happiness was not related to ADLs, but to social environment and information physical conditions.


[Application of visual analogue scale of happiness to elderly Himalayan highlanders]. Visual analogue scale of happiness (VAS-H) was applied to elderly Himalayan highlanders to investigate the influence of life-style and socio-cultural background on subjective happiness. The score of "VAS-H" and neuropsychological function tests in 733 Himalayan highlanders who belonged to 5 separate villages were compared with those in 313 Japanese elderly subjects. The places of study consisted of 4 villages (Khalimabad; K, Gulmit; G, Pasu; P, Shimshal; S) in Hunza area in Pakistan, and Namche Bazar; N in Nepal. Degree of modern civilization was highest in K, followed by N, G, P and lowest was that in S by historical and sociological aspects. The mean VAS-H sore in Himalayan highlanders and the degree of modern civilization in the area was in inverse proportion. Himalayan elderly women showed a significant lower score on VAS-H compared with elderly Himalayan men or elderly Japanese subjects. The VAS-H score in the Japanese elderly correlated significantly with the stability of posture and walk, and that of Himalayan highlanders correlated significantly with manual skill. In conclusion, the life style or socio-cultural background strongly affected subjective happiness in the elderly. The VAS-H was useful in comparing subjective happiness in different cultures.


[Upper gastrointestinal bleeding in the elderly]. Due to increasing number of the elderly, cases of hematemesis and melena in the aged have been increasing. The authors evaluated 69 such cases over 60 years old in whom emergency endoscopy of the upper digestive tract was carried out because of hematemesis and melena. Twenty cases are diagnosed as gastric ulcer (29%), 12 cases as esophageal ulcer and esophageal erosion (17.4%), 9 as duodenal ulcer (13.0%), 7 as gastric cancer (10.1%), 6 as Mallory-Weiss syndrome (8.7%), 6 as esophageal and gastric varices (8.7%), 4 as acute hemorrhagic gastritis (5.8%), 3 as Dieulafoy's ulcer (4.3%), and one case each of chronic pancreatitis (hemosuccus pancreaticus) and hemorrhage due to gastric angiodysplasia (1.4%). Of these cases, blood transfusion was performed in 46 cases (66.7%), and shock occurred in 27 cases (39.1%). The endoscopical hemostatic procedure was effective for detection of underlying diseases in the aged. Surgery was often impossible because of the rapid deterioration of the systemic condition due to the hemorrhage of the digestive tract.


[Post operative upper gastrointestinal bleeding in the aged]. A 10-year experience with 2,441 patients over 65 years of age undergoing operations for non-upper gastrointestinal tracts was reviewed to evaluate both the incidence of postoperative upper gastrointestinal bleeding and the clinical risk factors associated with the complication. A total of 18 (0.7%, 7 males and 11 females) patients had overt postoperative upper gastrointestinal bleeding of non-variceal origin documented by endoscopic findings or blood transfusions. Of these, the complication developed in 10 (1.5%) of 646 patients after an operation for biliary or pancreatic disease, 1 (1.5%) of 64 for aneurysmal or obstructive arterial disease, 5 (1.1%) of 43 for colorectal cancer and 2 (0.3%) of 916 for hernia. The incidences of bleeding after an operation for obstructive jaundice (3.8%), for biliary or pancreatic malignancy (4.5%), and of unavoidable diversion colostomy for colorectal anastomosis (3.1%) were significantly higher than for non-jaundice (0.6%), for non-malignancy (1.1%) and of postoperative upper gastrointestinal bleeding in the present study. The origins of bleeding were gastric ulcer in 11, acute gastric mucosal lesion in 4, duodenal ulcer in 1 and other in 2. All cases of bleeding were treated and met success in hemostasis using H2-blockers. Of these, however, 5 patients died of multiple organ failure despite discontinued hemorrhage, prophylactic use of H2-blockers showed a decrease in occurrence of postoperative upper gastrointestinal bleeding in the present study.


[Comprehensive activities of daily living (ADL) index for the elderly]. In order to measure disability in the elderly with a variety of handicaps a comprehensive activities of daily living (ADL) index is described. This instrument, named the ADL-20, consists of 20 items from four major categories of daily activities: (1) 5 items from basic ADL for mobility (BADLm), (2) 6 items from basic ADL for self-care (BADLs), (3) 7 items from instrumental ADL (IADL), and (4) 2 items from communication ADL (CADL). Each activity is scored on a four point scale with values from 0 (total dependency) to 3 (independency). In order to study the interrater reliability of the instrument 40 subjects were examined by a physician and physiotherapist independently at the University of Tokyo Hospital on the same day. Perfect agreement rates on the assignment of the disability score ranged from 70.0% to 97.5% with 85.6% in 800 paired examinations. The kappa values for perfect agreement ranged from 0.52 to 0.88. These results may guarantee a moderate or greater degree of interrater reliability. The correlation coefficients of the Spearman test on the rating scores by the physician and physiotherapist ranged from 0.66 to 0.99 in each activity with 0.97 in total score of 20 items. This scale was employed in 110 patients at the University Hospital and 106 patients staying in the nursing home or long-stay geriatric hospital in order to study its validity. The average age of those 216 patients, 77 males and 139 females, was 76.2 years old. The Cronbach alpha value concerning the consistency of each item as ADL assessment scale was 0.97.(ABSTRACT TRUNCATED AT 250 WORDS)


[Intellectual ability and activity of daily living of centenarians in institutions for the elderly]. The purpose of this study was to assess the intellectual ability and activity of daily living (ADL) of 12 centenarians in institutions for the elderly and to compare them with individuals in the 62-99 age group. At the time of our study, 66.7% of the centenarians were severely demented, three quarters of them suffering from Alzheimer's type dementia and the other one quarter the mixed type. There were qualitative differences between non-demented centenarians and the demented elderly in general, particularly in regard to understanding of surrounding objects and the presence or absence of mental symptoms indicating intellectual deterioration. A total of 50% of the centenarians were bedridden, but 41.7% of them could eat without assistance. Intellectual ability and ADL directly decreased with aging. We think centenarians do not present a special case and our clinical observations suggest a continuous process of aging. Five of the centenarians recently died and were autopsied. The agreement rate between clinical diagnoses and pathological findings with respect to dementia was 80%.


[Drug compliance in the elderly].

[Drug compliance in the elderly]. In order to clarify the characteristics of elderly patients concerning their attitudes toward taking prescribed medicine, self-reported compliance with prescriptions was compared among different age groups. We performed a survey in 626 outpatients and their attending physicians in 4 of our affiliated hospitals, and analyzed self-reported compliance by the patients to the prescription and their answers to questions related to drug-taking along with the diagnoses and prescriptions reported by the physician. The number of prescribed medicine was 2.3 tablets on the average for patients younger than 40, while 5.1 tablets were prescribed for patients over 70. However, self-reported compliance was best in patients over 70 than in other age groups. Compliance was good in 76% of patients who answered that the amount of medicine was appropriate, while good compliance was lower in those who thought the prescription excessive (67%). Likewise, compliance of patients who had concerns with drug side effects or who were not feeling well under medication was lower than that of patients who felt well under medication. Prescriptions for after lunch were most liable to be forgotten than those for other times of the day. Moreover, a high percentage of elderly patients attended more than 2 departments or medical facilities, and one third of those patients did not inform the physician of the fact suggesting that they were at higher risks of overdosing and unexpected drug interaction. Furthermore, the percentage of patients who did not receive explanation from physicians was higher in the elderly thus demonstrating that elderly patients have quite different characteristics in attitude with regard to medicine from younger age group patients.(ABSTRACT TRUNCATED AT 250 WORDS)


[Spinal bone mineral density in the female diabetic patients]. To investigate the frequency and etiology of diabetic osteopenia, we measured spinal bone mineral density (SBMD), total body bone mineral density (TBBMD), total body fat and lean body mass in 69 female diabetic patients (14 IDDMs and 55 NIDDMs). SBMD decreased with age in both IDDM and NIDDM, but when expressed as a percentage of age-matched normal Japanese females, some had lower SEMD, but others had normal or increased SBMD. Postmenopausal IDDM patients had lower SBMD than postmenopausal NIDDM patients. Thirteen out of 69 (18.8%) had an SBMD lower than 90% of age-matched controls. SBMD correlated positively with TBBMD. Those with lower SBMD had poor glycemic control, but there was no relation between SBMD and either duration of diabetes or presence of retinopathy and/or nephropathy. IDDM patients had lower 1.25 (OH)2D, osteocalcin than NIDDMs. SBMD correlated negatively with urinary pyridinoline and deoxypyridinoline excretion. SBMD correlated positively with body weight, and those with lower SBMD had significantly lower body mass index, body weight, fat weight and lean body mass than those with normal or increased SBMD. These results suggest that IDDM patients may be at higher risk of losing bone postmenopausally, and diabetic patients with lower SBMD have characteristics of poor diabetic control, lean habitus, low serum 1.25 (OH)2D.


[Protein binding of cephems in the elderly]. The serum protein-binding of 12 representative cephems (CET, CEZ, CZX, CPZ, CZON, CPM, CDZM, CFX, CMZ, CTT, LMOX, FMOX) was assessed, using sera from young healthy subjects (mean age, 28.6 years old) and elderly healthy subjects (mean age, 69.7 years old), applying equilibrium dialysis under the same conditions in vitro. The protein-binding capacity of 12 cephems in elderly subjects was significantly less than that in young subjects, and marked increase in free drug concentration was observed in elderly subjects. This decrease in the protein binding capacity of cephems in elderly subjects was possibly caused by decreased serum albumin and change in non-esterified fatty acid constitution related to aging. As free-drug concentration participates in the appearance of effects and adverse reactions, the possibility of an enhanced pharmacological effects and increased adverse reactions of cephems due to decrease of protein binding in elderly subjects should be considered.


[Pharmacokinetics of oral alminoprofen (Minalfen) in elderly patients with rheumatoid arthritis and spondylosis deformans]. The pharmacokinetics of oral Alminoprofen, a nonsteroidal anti-inflammatory drug, were studied in five elderly patients with rheumatoid arthritis and spondylosis deformans after 200 mg (three times a day) repeated dose for 5 days. The pharmacokinetic parameters after oral administration of Alminoprofen were analyzed by the one-compartment open model method. The maximum plasma concentrations (Cmax) were 16.1 +/- 2.5 micrograms/ml, after dosing on day 1, 25.2 +/- 1.6 micrograms/ml on day 3 and 21.6 +/- 2.7 micrograms/ml on day 5. The maximum time (Tmax) were about 2 hours after the medication in al cases. The area under the curve in drug concentration in plasma versus time (AUC) were 58.5 +/- 6.3 micrograms hr/ml on day 1, 58.5 +/- 3.1 micrograms hr/ml on day 3 and 58.1 +/- 8.5 micrograms hr/ml on day 5. The biological half-lives (t1/2) were 2.45 +/- 0.35, 2.09 +/- 0.82 and 2.49 +/- 0.63 hours, after dosing on day 1, day 3 and day 5, respectively. The analysis of moment in pharmacokinetics revealed that the mean residence time (MRT) on day 1, day 3 and day 5 observed were 2.31 +/- 0.03, 2.15 +/- 0.09 and 2.15 +/- 0.07 hours, respectively. The variance residence times (VRT) observed were 0.95 +/- 0.05 hour2 on day 1, 0.88 +/- 0.09 hour2 on day 3 and 1.06 +/- 0.07 hour2 on day 5. The ratios of accumulation calculated were 1.16 +/- 0.05 in both the morning medication on day 3 day 5, and it therefore appears that the steady-state equilibrium is established within 3 days after commencement of dosage.(ABSTRACT TRUNCATED AT 250 WORDS)


[Diagnostic value of a new myocardial perfusion agent, 99mTc-teboroxime (SQ30,217) in patients with coronary artery disease, utilizing a SPECT imaging protocol: a multicenter phase III clinical trial]. Technetium-99m teboroxime (TEBO) is a new technetium-based myocardial perfusion imaging agent, which has high myocardial extraction and rapid myocardial washout. Its rapid myocardial washout may necessitate rapid imaging protocols. This study was designed to perform exercise/rest SPECT imaging protocols with rapid data acquisition (from 2.8 +/- 1.4 min to 11.2 +/- 4.1 min after injection) in 171 patients with coronary artery disease, 15 patients with cardiomyopathy and 8 patients with other heart disease. The rapid imaging protocols resulted in a high prevalence of good image quality. The diagnostic value of TEBO was recognized from the high concordance of image findings with thallium-201 (201Tl) scintigraphy, 88.2% in the exercise protocol and 89.9% in the rest protocol. Also, the sensitivity and specificity of TEBO for detecting coronary artery disease were comparable (86.6% and 53.9%, respectively) with those of 201Tl (90.7% and 46.2%, respectively). No toxic effects of TEBO were observed in subjective and objective clinical findings and blood examinations. TEBO was finally evaluated to be useful in 98.4% of the patients. Thus, this agent has good clinical potential for myocardial perfusion imaging.


[Three-phase bone scintigraphy of Kienböck disease]. Thirty-three joints in 31 patients of Kienböck disease were evaluated with three-phase bone scintigraphy. Follow-up studies were performed in 19 cases of them. The patients with increased ulnar blood flow on arterial phase and ample perfusion on venous phase in angiograms showed good clinical prognosis. This ample ulnar blood flow and perfusion might be essential for the recovery of this disease. Although staging was possible using static images alone, blood pool images provided more information about the present condition of lesions, such as hyperemic state and remodeling reactions. Blood pool image was indispensable for staging and analyzing lesions and evaluating post-operative course. Increased lunate perfusion in venous phase of angiograms and localized lunate uptake in blood pool images were the favorable signs, which were shown in most cases with good prognosis. It is concluded that three-phase bone scintigraphy gives useful informations for evaluating Kienböck disease which can not be obtained by conventional bone scintigraphy.


[Usefulness of 99mTc-ECD SPECT in diseases of the central nerve system: special reference to a comparison with 123I-IMP and 99mTc-HM-PAO SPECT]. The usefulness of a new cerebral perfusion imaging radiopharmaceutical, 99mTc-ethyl cysteinate dimer (ECD), was clinically evaluated. The subjects of this study were 14 patients with neurological disorders including 10 patients with cerebral infarction and 4 patients with other diseases. A total of 15 examinations was performed. 99mTc-HM-PAO or 123I-IMP SPECTs were performed simultaneously, and the findings from those examinations were compared with 99mTc-ECD. As to the count ratio of lesions to normal area (L/N), the L/N ratio in severe ischemic patients was lower in 99mTc-ECD than in 99mTc-HM-PAO or 123I-IMP. In mild ischemic patients, on the other hand, the L/N ratio was the lowest in 123I-IMP. When the relationship between rCBFs obtained from 123I-IMP and the values of L/N in 99mTc-ECD or 99mTc-HM-PAO was compared, the values of L/N in 99mTc-ECD or 99mTc-HM-PAO were found to have decreased linearity with increasing rCBF. In a patient showing luxury perfusion, the accumulation pattern of 99mTc-ECD was different from that of the other two radiopharmaceuticals, and focal defect was revealed in 99mTc-ECD SPECT. On the dynamic SPECT of 99mTc-ECD in a patient with meningioma, the tumor showed a change from high to low perfusion with the passage of time. This finding indicated that care should be taken in the evaluation of accumulation of 99mTc-ECD. Therefore, 99mTc-ECD was found to be useful as a cerebral perfusion agent. In addition, as accumulation of 99mTc-ECD might somehow reflect metabolism in some cases, further careful investigation of many cases should be carried out.


[Clinical usefulness of the quantitative assessment of exercise thallium-201 myocardial imaging in patients with ischemic heart disease]. To clarify the significance of the quantitative analysis of the area of decreased activity in exercise thallium-201 myocardial imaging, 42 patients with one vessel disease (20 patients with angina pectoris without myocardial infarction, 22 patients with old myocardial infarction: MI) were evaluated by exercise thallium scan and compared with clinical findings and wall motion assessed by left ventriculography (LVG). Patients with MI were divided into two groups by LVG (Mild MI: MI with only hypokinesis on LVG, Severe MI: MI with akinesis or dyskinesis on LVG). The degree of defected area was expressed by the ratio of the counts of defected area to the normal area (Relative Activity: RA). RA of the area of decreased activity in patients with angina was higher than that of patients with MI (77.5 +/- 4.59% vs. 65.7 +/- 7.85%, p < 0.05). RA of the area of decreased activity in patients with mild MI was higher than that of patients with severe MI (69.5 +/- 4.78% vs. 61.3 +/- 8.45%, p < 0.01). The above results suggest that the regional thallium-201 uptake ratio in the scintigram may help to differentiate viable zones from necrotic ones and detect the degree of MI.


[Quantitative analysis of sodium fast and slow component in in vivo human brain tissue using MR Na image]. In vivo sodium concentrations in the normal brain tissue and a tumorous tissue were analyzed using MR Na image. The nuclear magnetic resonance enabled us to divide the signal from sodium in the living tissue into 2 parts based on the differences of T2 value. Those are fast component having the T2 value of less than 5 msec and slow component of 15-40 msec. We investigated the effect of macromolecules on T2 value of sodium image using polyvinyl alcohol (PVA) powder. MR Na image was taken with the parameters of TR/TD, 110 ms/1.9 ms (FID image) and TR/TE, 110 ms/20 ms (SE image). Saline solution showed high intensity on both FID image and SE image. Saline solution added PVA (PVA phantom) also showed high intensity on FID image, whereas the signal intensity of PVA phantom in SE image extinguished. To know the relation between the signal intensity and sodium concentration, sodium concentration--signal intensity curve was obtained using phantoms with various sodium concentrations (0.05-1.0%). This curve showed a direct proportion between sodium concentration and signal intensity on Na image. We measured further the sodium concentrations of the human brain tissue. Sodium phantoms were arranged around the heads and the MR Na images of the normal brains from 3 volunteers and a patient with a brain tumor (meningioma) were taken. The sodium concentrations of occipital lobe, basal ganglia and the tumorous tissue were calculated using the sodium concentration--signal intensity curve obtained from the phantoms arranged around the heads.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of scattering and spatial resolution on SPECT quantification values: experimental study using phantoms and clinical application]. The relative SPECT values are often inaccurate by the scattering and limited spatial resolution of single photon emission CT (SPECT). These effects were studied using phantoms and some attentions on clinical application were investigated. Using cylindrical phantom divided into six compartments filled with various radioactivities, the linear correlation between SPECT value and radioactivity, and also correlation with partial reduction of radioactivity were identified. But the SPECT value was relatively increased in proportion to the reduction of radioactivity due to the increase of scattering contribution. The SPECT value represented lower radioactivity when the cortical thickness was smaller than two times of FWHM and represented half radioactivity when the cortical thickness was equal to FWHM. Excellent correlation between SPECT value and radioactive partial volume averaging of brain with CSF was recognized using our hand made phantom simulating various degree of atrophic brain. It is very important to compare SPECT image with X-CT or MR image to avoid misreading taking the above mentioned effects due to scattering and limited spatial resolution.


[Quantification of regional cerebral blood flow using 99mTc-HMPAO SPECT and intravenous 133Xe injection method]. We converted an absolute value of 133Xe-CBF (initial slope index, ISI) to the three dimensional CBF-SPECT using the intravenous 133Xe injection technique and 99mTc-HMPAO SPECT according to the microsphere model (method A), and the three compartment model described by Lassen et al. (method B): [formula: see text] [formula: see text] where f = flow in the region of interest (ROI), fr = flow in the reference region, C = count density of 99mTc-HMPAO SPECT in the ROI, Cr = count density of 99mTc-HMPAO SPECT in the reference region, and alpha = conversion to clearance ratio of HMPAO. We used alpha value of 1.5, and the whole cerebrum as a reference region. Four asymptomatic subjects and 15 patients with ischemic cerebrovascular disease were entered the study. In method A, excellent correlation was seen between ISI and SPECT-CBF in both of the cerebral hemisphere (r = 0.993; p < 0.001, n = 38) and the cerebellar hemisphere (r = 0.901; p < 0.001, n = 38). When back diffusion of HMPAO was corrected by method B, correlation coefficient of SPECT-CBF with ISI was equivalent to that in method A in the cerebrum (r = 0.978; p < 0.001, n = 38), while the correlation coefficient ih the cerebellum was lowered (r = 0.726; p < 0.001, n = 38) although high flow to low flow ratio was increased. Reproducibility of rCBF assessed 1 week apart from the first CBF-SPECT was highly reproducible in all of the brain regions; correlation coefficient ranged from 0.757 to 0.910 with a mean correlation coefficient of 0.834 (n = 11). The slope and intercept of the linear regression line between 2nd rCBF versus 1st CBF were 0.889 (range, 0.791-1.141) and 5.5 (range, -9.1-13.4), respectively. Regional CBF measured by method B was approximately 20% increase from that measured by method A. However, there was no significant difference in the reproducibility of rCBF between the two methods. Our results indicate that rCBF can be simply and noninvasively quantified using 99mTc-HMPAO SPECT and absolute unit of CBF measured by 133Xe injection technique. SPECT-CBF offers high resolution images and may be applicable for various cerebrovascular disorders in routine clinical use.


[Unsuspected painless subacute thyroiditis detected by radiogallium scintigraphy]. Two cases of painless subacute thyroiditis were presented in whom fever, fatigue and arthralgia except for thyroidal pain and swelling were complained. Until a intense uptake of the thyroid was found on radiogallium scintigraphy, the examinations of the thyroid had not been done. Laboratory data showed increased erythrocyte sedimentation rate, C-reactive protein and serum alkaline phosphatase, and mild leukocytosis. Skeletal, hepatic and biliary diseases were denied. In patients who have fever, increased erythrocyte sedimentation rate and serum alkaline phosphatase elevation without apparent sources, thyroid function should be evaluated because subacute thyroiditis can be associated with elevation of the serum alkaline phosphatase.


[Clinical study on the time courses of serum myosin light chain I levels in patients with acute myocardial infarction: effect of intracoronary thrombolysis on serum myosin light chain I levels]. Changes of serum myosin light chain I (Myosin LCI) concentrations and CK activities were serially measured in 23 patients with acute myocardial infarction. Intracoronary thrombolysis was performed in 14 patients (ICT group) while the remaining 9 patients were treated in the conventional manner (non ICT group). The relationships between the maximum levels of serum Myosin LCI or CK and a myocardial infarct size index or left ventricular function were evaluated in 18 patients. The myocardial infarct size index was determined by 201Tl myocardial scintigrams performed in the chronic phase. Multiple peaks of Myosin LCI were observed in 64% (9/14) of the ICT group and the first peak in 6 of these patients appeared Much earlier in the same time as CK peak than in the non-ICT group, while multiple peaks were seen only in one case in the non-ICT group. The infarct size index by 201Tl myocardial SPECT correlated with maximum Myosin LCI levels (r = 0.88, p < 0.001, n = 10) and CK activities (r = 0.67, p < 0.05, n = 10). These results indicate that the measurement of serum Myosin LCI is very useful for estimating the extent of myocardial damage and suggest that myocardial degeneration occurs at a very early phase of myocardial infarction.


[Metabolite of 15-p-iodophenyl-3(R,S)-pentadecanoic acid (123I) in blood and urine]. We analyzed metabolites of 123I-BMIPP in blood and urine using rats, rabbits and human, while human samples were obtained from normal volunteers of Phase I clinical study. We estimated metabolic pathway of 123I-BMIPP as a myocardial metabolic imaging agent. Radioactivity accumulated in heart after administration gradually decreased and was mainly excreted to bladder via kidneys. The main radioactive component in blood was 123I-PIPA for any species and the urinary components were metabolic conjugates of 123I-PIPA. As results of these studies, we considered that 123I-BMIPP was metabolized to 123I-PIPA by alpha-oxidation process for the first step, follow by beta-oxidation process, then 123I-PIPA was released to blood from tissues. Moreover, 123I-PIPA in blood was conjugated with other compounds and excreted to the bladder.


Evidence for phase-locking response to hypoxia in peripheral chemoreceptor activity in man. A number of animal studies have demonstrated that the ventilatory response to stimulation of the peripheral chemoreceptors is well reproduced only when it is stimulated during inspiratory period. In humans, such a response has not been confirmed when using a mild hypoxic stimulus. We, therefore, hypothesized that this response may be detected when a more intense hypoxia is applied. To confirm this hypothesis, six healthy subjects inhaled N2 gas mixture with 5% CO2 in an amount of vital capacity. This procedure started from steady state mild hypoxia (PET02; 60-70 mmHg). Inspiratory and expiratory minute ventilation (VI and VE), tidal volume (VT), and inspiratory and expiratory time (TI and TE) of the breath, at the start of falling oxygen saturation, were analyzed. 21% O2 + 5% CO2 balanced with N2 was inhaled and a breath cycle with a similar latency as during N2 gas mixture inhalation was also analyzed as a control. When oxygen saturation began to drop at the inspiratory phase, the increment of ventilation and tidal volume were larger than the control. When it occurred at the expiratory phase, no significant difference from the control was seen. These results signify the presence of rectification of chemoreceptor afferent signal in humans and may support the concept of oscillation hypothesis as an effective ventilatory stimulus.


Caffeine and theophylline contractures in tonic skeletal muscle fibers of the frog. Caffeine and theophylline evoke maintained tension in tonic skeletal muscle fibers of the frog. Their effects depended upon concentrations ranging from 0.5 to 14 mM. The resting potential of tonic skeletal fiber was unaffected by caffeine or theophylline (4 mM). Caffeine and theophylline contractures have a peak tension followed by a sustained tension, which recovered spontaneously when returned to normal solution. The peak tension and total tension (the area under tension-time curve) were reduced when the fibers were soaked in calcium-free solution. In addition the tension was reduced by calcium channel blockers (cadmium). The sustained tension was increased when external calcium was raised. These results suggest that caffeine and theophylline promote the calcium release from sarcoplasmic reticulum and probably the entry of calcium from external medium.


Axon reflex flare evoked by nicotine in human skin. (1) The purpose of the present study is to investigate whether or not the vasodilatation evoked by intradermal (I.D.) injection of nicotine is mediated through axon reflex mechanism, and to examine the involvement of histamine receptors or capsaicin-sensitive C-fibers in nicotine-induced vasodilator response, using a band method and a laser Doppler technique. (2) The vasodilator response, whether it was caused by nicotine or histamine, developed as quickly on the uninjected side as on the injected side of the band, while the wheal reaction was elicited only by histamine and was localized in the injection side of the band. (3) Pretreatment with either a local anesthetic (lidocaine) or 1% capasaicin markedly reduced the nicotine- and histamine-induced blood flow responses, whereas pretreatment with antihistaminergic agent (diphenhydramine) showed inhibitory effect to the blood flow response only to histamine. (4) These data suggest that two types of chemical receptors, i.e. the nicotinic and the histamine-sensitive receptors, exist in capsaicin-sensitive C-fibers to elicit axon reflex vasodilatation in human skin.


Somatosensory regulation of regional hippocampal blood flow in anesthetized rats. The effect of noxious or non-noxious mechanical stimulation of various cutaneous areas on cerebral blood flow in hippocampus was examined with laser Doppler flowmetry in urethane-anesthetized artificially-ventilated rats. Noxious mechanical stimulation (pinching) of the skin on the face, forepaw, chest, or hindpaw for 20s increased regional hippocampal blood flow (Hpc-BF) and systemic blood pressure, but non-noxious mechanical stimulation (brushing) had no such effect. After the spinal cord was transected at T1 level a forepaw pinch caused no change in blood pressure but still increased Hpc-BF. This suggests that cutaneous noxious stimulation can induce pressor-independent increases in Hpc-BF. The increase in Hpc-BF induced by a forepaw pinch in T1-transected rats was partially reduced by intravenous administration of mecamylamine (2 mg/kg), a nicotinic cholinergic receptor antagonist. Atropine (0.5 mg/kg), a muscarinic cholinergic antagonist was ineffective. These data indicate that the cholinergic vasodilative system is involved in the somatically-induced increase in Hpc-BF via activation of the nicotinic cholinergic receptors.


Inhibition of arterial baroreceptor reflex during coronary artery occlusion. The sensitivity of baroreceptor reflex during myocardial ischemia induced by acute occlusion of left anterior descending coronary artery (LAD) was studied in anesthetized, artificially ventilated, and thoracotomized dogs. Occlusion of LAD attenuated the baroreflex mediated changes in heart rate (HR) in response to changes in arterial pressure (AP) in the animals with intact autonomic nervous system (ANS). The HR increased significantly with the time of occlusion of LAD in control (ANS) as well as in beta-blocked group, suggesting vagal inhibition. In atropinized and vagotomized animals, the HR remained unchanged following LAD occlusion. In control group, the sensitivity of baroreflex mediated tachycardia response to hypotension and bradycardia response to hypertension, after 4 h of LAD occlusion, was reduced. In beta-blocked animals, the tachycardia response after LAD occlusion was drastically reduced to almost zero. The peak sensitivity of baroreflex bradycardia response was reduced in atropinized and vagotomized animals while the peak sensitivity of baroreflex tachycardia response increased after vagotomy. In contrast, bradycardia response was increased after beta-blockade. These data indicate that acute LAD occlusion attenuates arterial baroreflex control of HR and reduction of baroreflex sensitivity is mediated by parasympathetic efferents.


Effect of verapamil on ventilatory and circulatory responses to hypoxia and hypercapnia in normal subjects. Recent investigations have shown that the calcium channel blocker verapamil attenuated the hypoxic ventilatory chemosensitivity of carotid body in animals. To determine whether this is also the case in humans, transient physiological chemodenervation by O2 breaths (withdrawal test) during sustained hypoxia (N = 7), and ventilatory and circulatory responses to progressive hypoxia and hypercapnia (N = 8) were examined after oral administration of verapamil. During sustained hypoxia after verpamil, there was a significant reduction of withdrawal response from 5th to 25th min value (p < 0.01), but not after placebo. On the other hand, no significant difference in ventilatory responses to progressive hypoxia and hypercapnia was observed after verapamil. Verapamil run reveals similar features with placebo run in circulatory parameters except blood pressure response, which tended to be suppressed by verapamil. We conclude that verapamil attenuates peripheral chemoreceptor activity with time during sustained mild hypoxia in normal adult humans and this may be explained by delayed depletion in intracellular Ca2+ for chemotransduction of the peripheral chemoreceptors.


Changes in blood volume and potassium concentration during exercise in rats. We measured the changes in circulating blood volume (BV), plasma sodium ([Na+]), and plasma potassium ([K+]) concentrations continuously, during and after exercise in euhydrated and dehydrated rats. Rats ran on a treadmill for 15 min at 600, 900, and 1,200 m/h, and the recovery period lasted 45 min. The BV decreased immediately after onset of exercise, and reached a plateau value in about 5 min of exercise. With 1,200 m/h exercise, a further decrease in blood volume was observed in both groups. The decline in BV was reversely related to the exercise intensity in both groups although the decrease was less in the dehydration group. During and after exercise, there were no significant changes in plasma [Na+] at any speed in either group. Plasma [K+] increased sharply at the onset of exercise and the magnitude of the increase was directly related to the exercise intensity. However, at all three exercise intensities the change in plasma [K+] in the dehydrated group was only about 60% of that measured in the euhydrated control group. These findings suggest that dehydration reduces the wash-out of K+ from the interstitial space of the exercising muscle.


Somatic afferent stimulation-plasma corticosterone, luteinizing hormone (LH), and testosterone responses in aged male rats under anesthetization. Our previous studies have demonstrated that somatic sensory stimulation can produce increases in secretions of corticosterone, luteinizing hormone (LH), and testosterone in young male Wistar rats of 13-22 weeks old even after emotional factors are eliminated by pentobarbital-anesthetizing of the subjects. In the present study, we examined the effects of somatic sensory stimulation on plasma corticosterone, LH, and testosterone using aged male Wistar rats (24-27 months old) under the same anesthetizing condition as employed in our previous studies. We compared the reflex responses in aged rats with those previously measured in young rats. Nociceptive mechanical stimulation of both hindpaws by pinching for 10 min significantly increased plasma corticosterone levels in aged rats. The magnitude and time-course of this response were equivalent to those in young rats. On the other hand, neither plasma LH nor testosterone levels were changed by nociceptive mechanical stimulation of the hindpaws of aged rats. This is in sharp contrast to the increase in both plasma LH and testosterone caused by the stimulation of young rats. These results indicate a functional dissociation induced by aging between the secretory responses of the anterior pituitary, testes on the one hand and the adrenal cortex on the other hand, to nociceptive somatic sensory stimulation. Aging does not alter corticosterone release from the adrenal cortex to nociceptive somatic sensory stimulation; however, LH secretion from the anterior pituitary and testosterone secretion from the testes to nociceptive somatic sensory stimulation are subject to dysfunction with aging.


Heat production associated with a propagated impulse in bullfrog myelinated nerve fibers. By using heat-sensors constructed with thin film of polyvinylidene fluoride, it was found possible to detect the heat generated by myelinated fibers in the bullfrog sciatic nerve in association with a propagated impulse. The quantity of heat generated (about 0.4 microcal/g at 4.5 degrees C) is roughly two orders of magnitude smaller than that observed in nerves containing only non-myelinated nerve fibers. The smallness of the heat observed is attributed to the localization of the heat sources at the nodes of Ranvier. The major portion of the heat generated is re-absorbed by the nerve.


Contractile activity and fluorescence changes in fluo-3-loaded isolated ventricular myocytes. Isolated rat ventricular myocytes were loaded with fluo-3 which did not result in a loss of beating activity, in order to record the changes in the fluorescence and contractile parameters. Changes in the beating activity induced by various reagents in perfusing medium were related to variations in the peak intensity of fluorescence time course and possibly to changes in myofibrillar ATPase activity. Isoproterenol stimulated, whereas 2,3-butanedione monoxime (BDM) and a medium with a low Ca2+ concentration suppressed the contractile activity by increasing and reducing the Ca2+ transient, respectively, and, in the presence of BDM, a decrease in the maximum ATPase activity also contributed the suppressive effect.


Effects of acute hypoxia on ventilatory response at the onset of cycle exercise in man. In order to examine whether or not there are initial changes in ventilation at the start of bicycle exercise having work loads of differing intensities are affected with regard to normoxia and to hypoxia accompanying hypocapnia, six healthy male subjects performed submaximal exercise of 30 and 120 W at 60 rpm under normoxic (FIO2 = 0.21) and hypoxic (FIO2 = 0.11) conditions. Resting ventilation was significantly higher in hypoxia than in normoxia. However, no statistically significant differences in the initial change in ventilation at the start of exercise (delta VI assessed breath-by-breath) were found between eucapnic normoxia and hypocapnic hypoxia in both 30 and 120 W exercise. Moreover, blood lactate after exercise did not increase in any conditions as compared with rest. These observations suggest that the neurogenic ventilatory response immediately after submaximal exercise at a work load below the subject's anaerobic threshold is independent from PO2.


Epinephrine and norepinephrine release from bullfrog gastrointestinal sympathetic postganglionic endings at a high ambient temperature. The influence of a high ambient temperature on sympathetic neurotransmitter release in bullfrogs was studied. Gastrointestinal vascular perfusates were collected before and after splanchnic nerve stimulation, and their content of epinephrine and norepinephrine was determined. A marked increase in epinephrine and norepinephrine release was observed following stimulation at 29-32 degrees C, indicating that epinephrine and norepinephrine may both act as adrenergic transmitters in a high-temperature environment.


Chronopharmacology of furosemide in rats with amikacin-induced acute renal damage. To examine the influence of amikacin-induced acute renal damage on the urinary excretion of furosemide and the time-dependent variation in the urinary amount of the agent, amikacin (1.2 g/kg) was given intraperitoneally to Wistar rats. Study I: Three percent b.w. of 1% NaCl solution was given orally before and after amikacin treatment, and an 8-hour urine for N-acetyl-beta-D-glucosaminidase (NAG) was collected. Study II: Furosemide (30 mg/kg) in 3% b.w. of 1% NaCl solution was given orally at 12 a.m. or 12 p.m. before and after amikacin treatment, and an 8-hour urine for sodium and furosemide was collected. Following amikacin treatment, urinary excretion of NAG increased, while urine volume and urinary excretion of sodium and furosemide decreased. Urinary excretion of furosemide and its diuretic effects were significantly greater at 12 a.m. than at 12 p.m. before and after treatment. However the time-dependent differences in these parameters were diminished by amikacin treatment. These results suggest that the urinary excretion of furosemide is reduced and the extents of the time-dependent variation in the urinary furosemide and its diuretic effects are altered in rats with amikacin-induced renal damage.


Characterization of the triphenyltin-induced increase in intracellular Ca2+ of mouse thymocytes: comparison with the action of A23187. The properties of triphenyltin (TPT) in increasing intracellular Ca2+ ([Ca2+]i) of thymocytes was studied, in comparison with those of A23187, by the use of fluorescent dyes to monitor membrane potential and [Ca2+]i. Both 1 microM TPT and 30 nM A23187 increased the [Ca2+]i associated with the hyperpolarization mediated by Ca(2+)-dependent K+ conductance. The time course for the TPT-induced increase in the [Ca2+]i was much slower than that of A23187. When the external Ca2+ ([Ca2+]o) was removed, TPT produced a slight, but persistent, increase in the [Ca2+]i while A23187 caused only a transient increase in the [Ca2+]i. Reintroduction of Ca2+ to the external solution produced an increase in [Ca2+]i in both cases. Therefore, these results suggested that the increase in the [Ca2+]i of thymocytes induced by TPT and A23187 was dependent on the presence of [Ca2+]o and an intracellular Ca store. The potency of TPT in increasing the [Ca2+]i was greater than those of diphenyltin and monophenyltin, suggesting an involvement of the lipophilic property of organotins in increasing [Ca2+]i. The TPT-induced increase in the [Ca2+]i may be partly responsible for the toxicity of TPT on organs and/or organ systems.


Studies on the antinephritic effects of plant components (6): antinephritic effects and mechanisms of phellodendrine (OB-5) on crescentic-type anti-GBM nephritis in rats (2). Effects of phellodendrine (OB-5) on crescentic-type anti-GBM nephritis in rats and the cell number of the various leukocyte subpopulations in the glomeruli of the nephritic rats were investigated. OB-5 at 25, 50 and 100 mg/kg/day, p.o. prevented the urinary protein excretion by the 19th day after i.v.-injection of anti-GBM serum. In the OB-5-treated rats, plasma cholesterol and creatinine contents were lower than those of the control rats throughout the 40-day experimental period. Histopathological observations demonstrated that OB-5 inhibited the incidence of crescent formation, adhesion and fibrinoid necrosis in the glomeruli by the 41st day. OB-5 did not affect the plasma antibody titer against rabbit gamma globulin. The increases in total leukocytes, macrophages, cytotoxic/suppressor T cells, Ia positive cells, and IL-2 receptor positive cells in the glomeruli in OB-5, 100 mg/kg-treated rats as well as those of the animals treated with azathioprine or cyclosporin A were lower than those of the anti-GBM nephritic control. These results indicate that OB-5 was effective in crescentic-type anti-GBM nephritis and the antinephritic mechanisms of this agent may be due to its ability to inhibit the proliferation or the migration of macrophages and cytotoxic T lymphocytes in the glomeruli.


In vitro antagonism of ONO-1078, a newly developed anti-asthma agent, against peptide leukotrienes in isolated guinea pig tissues. We evaluated the antagonist activity of ONO-1078 against peptide leukotrienes (LTs) by a radioligand binding assay and functional experiments in guinea pigs. In the radioligand binding assay, ONO-1078 inhibited [3H]LTD4 and [3H]LTE4 bindings to lung membranes (Ki = 0.99 and 0.63 nM, respectively) and was 2,000- to 3,000-fold more potent than FPL55712. Antagonism of ONO-1078 against [3H]LTC4 binding (Ki = 5640 nM) was approximately twofold more potent than that of FPL55712. The antagonism of ONO-1078 against [3H]LTD4 binding was competitive. In functional experiments, ONO-1078 showed competitive antagonism against the LTC4- and LTD4-induced contractions of guinea pig trachea and lung parenchymal strips with a pA2 range of 7.70 to 10.71 and was approximately 400- to 3,300-fold more potent than FPL55712. Interestingly, in the presence of an inhibitor of the bioconversion of LTC4 to LTD4, ONO-1078 also antagonized the LTC4-induced contraction of guinea pig trachea (pA2 = 7.78). ONO-1078 significantly reversed the LTD4-induced prolonged contraction without effect on the KCl- and BaCl2-induced contractions of guinea pig trachea. Furthermore, ONO-1078 antagonized the antigen-induced SRS-A mediated contraction of guinea pig trachea. On the other hand, ONO-1078 showed no antagonism against histamine, acetylcholine, 5-hydroxytryptamine, prostaglandin D2 and U-46619. In addition, ONO-1078 showed little or no effect on the activities of cyclooxygenase, 5-lipoxygenase and thromboxane synthetase. These in vitro studies indicate that ONO-1078 is a highly potent, selective and competitive antagonist of peptide leukotrienes that acts with higher affinity at LTD4 and LTE4 receptors than LTC4 receptors.


Removal of extracellular Mg2+ suppresses sulfation of glycoconjugates secreted from rabbit trachea in culture. The influences of extracellular Ca2+ and Mg2+ concentrations on the basal secretion of glycoconjugates from rabbit trachea in organ culture were examined. Over 80% of the 35S-labeled and [3H]glucosamine-labeled glycoconjugates secreted by the trachea were digested upon incubation with chondroitinase ABC. The basal secretion did not occur in the medium at 4 degrees C, indicating an energy-dependent process. The basal secretion at 37 degrees C of 35S-labeled glycoconjugates was prominently suppressed in Mg(2+)-free Tyrode solution but not in Ca(2+)-free Tyrode solution containing ethyleneglycol bis(2-aminoethylether)tetraacetic acid (EGTA). In contrast, the basal secretion of [3H]glucosamine-labeled glycoconjugates was not affected by the Mg2+ concentration in the medium. The results suggest that extracellular Mg2+ largely contributes to sulfation of glycoconjugates basally secreted from rabbit trachea.


Regional hemodynamic effects of betaxolol, a new selective beta 1-blocker, and atenolol in conscious spontaneously hypertensive rats. Betaxolol is a new beta-blocker that has been reported to have beta 1-selectivity, and it is devoid of both membrane stabilizing action and intrinsic sympathomimetic action. The effects of betaxolol on systemic and regional hemodynamics were examined in conscious spontaneously hypertensive rats (SHR) by a microsphere method and compared with the effects of atenolol. A single oral administration of betaxolol at 1 and 10 mg/kg decreased the mean arterial pressure in a dose-dependent manner. At the same doses, atenolol also showed a similar but weak hypotensive effect. Both of these drugs at the high dose decreased cardiac output and heart rate and at the low dose, did not. Total peripheral resistance decreased by only betaxolol at the low dose. Betaxolol showed a tendency to normalize the hemodynamic abnormalities which were observed in the kidney, spleen and gastrointestinal tract of SHR, while atenolol did not. It should be noted that betaxolol increased the flow rate in the kidney, which may be explained by its direct vasodilatory action on renal blood vessels. In conclusion, betaxolol showed an antihypertensive action at the doses of 1 and 10 mg/kg, exhibited the characteristics of a beta 1-blocker and produced preferable effects on regional hemodynamics in SHR.


Evidence that stretch receptors for peristalsis are located in the mucosal layer of the guinea pig ileum. Location of stretch receptors triggering the peristalsis was investigated in the isolated guinea pig ileum. Peristalsis was cyclically induced by perfusing the lumen with Krebs solution flowing at a constant rate. Peristalsis was promptly abolished by serosally applied 3 x 10(-7) M tetrodotoxin, 10(-4) M lidocaine, 10(-6) M morphine or 10(-5) M nicotine, confirming the claim that peristalsis was neurally regulated by the myenteric plexus. Intraluminal application of 3 x 10(-7) M tetrodotoxin not only blocked the peristalsis, but also inhibited the contractions of the longitudinal muscle elicited by transmural stimulation or 10(-4) M nicotine by the same extent as those by serosal tetrodotoxin, suggesting that the blockade of peristalsis was due to the tetrodotoxin infiltrating into the muscle layer. In contrast, intraluminal application of 0.1% glutaraldehyde or perfusing the lumen with the low NaCl (20 mM)-containing Krebs solution abolished the peristalsis without critically inhibiting the neurogenic contractions of the longitudinal muscle, indicating that the blockade of peristalsis by these intraluminal treatments was ascribed to the actions on the mucosal layer. These results may imply that stretch receptors are located in the mucosal layer of the guinea pig ileum, and the impairment of the functions of these receptors by the intraluminal treatments leads to the blockade of the peristalsis.


Effects of standard cigarette smoke and nicotine-reduced cigarette smoke on plasma concentrations of indomethacin administered orally to rats. The influence of acute exposures to standard (ST) and nicotine-reduced (NR) cigarette smokes on the plasma concentration of orally administered indomethacin (IM, 5 mg/kg) was investigated in rats. IM plasma concentrations in the ST- and NR-groups were lower than those in the non-smoking control group, while the lowered effect in the NR-group was slightly weaker than in the ST-group. These results suggest that the plasma concentrations of IM administered orally are lowered by the acute exposure of cigarette smoke, and this influence may be attributed largely to constituents other than nicotine in the cigarette smoke as well as slightly attributable to nicotine.


Effects of isolation housing and timing of drug administration on theophylline kinetics in mice. ICR mice were grouped according to 1) housing environment: individual (I) or aggregated (A) and 2) timing of drug administration: midlight (L) or middark (D), i.e. I-L, I-D, A-L, A-D groups. Theophylline was orally administered at midlight or middark. The results showed that both social environment and timing of drug administration exerted significant influence on the pharmacokinetics of theophylline. These data may suggest the importance of considering many non-drug factors in toxicological studies with experimental animals.


ATP-sensitive K+ channels are gradually recruited in the vasodepressor response to adenosine in spinally-anesthetized dogs. Vasodepressor mechanisms of adenosine were investigated in spinally-anesthetized dogs. An i.v.-infusion of adenosine (0.1-10 mumol/kg/min) caused a slowly developing and sustained decrease in blood pressure (BP). This vasodepression was antagonized by glibenclamide, a blocker of ATP-sensitive K+ (KATP) channels. On the other hand, a transient decrease in BP caused by a single bolus i.v.-injection of adenosine was not antagonized by glibenclamide in our previous study. These results suggested that the opening of KATP channels is gradually recruited in the vasodepressor mechanisms for adenosine-induced sustained vasodepression.


Kangenkaryu prevents the decrease of cholinergic markers following the nucleus basalis magnocellularis lesion. The nucleus basalis magnocellularis (nbm)-lesioned rat is considered to be a model of the cholinergic dysfunction observed in the cerebral cortices of Alzheimer's disease patients. The cholinergic markers, acetylcholine release and choline acetyltransferase activity, were decreased in the cerebral cortex of the nbm-lesioned rat. Kangenkaryu (KAN), a Chinese traditional medicine, is a typical prescription for the treatment of symptoms related to blood circulation deficiency. Orally administered KAN following the nbm lesion significantly preserved the cholinergic markers. The present results indicate that KAN may preserve the activity of cholinergic neurons in the cerebral cortex after the nbm lesion.


In vivo release of dopamine by perfusion of 1-methyl-4-phenylpyridinium ion in the striatum with a microdialysis technique. We examined the effects of 1-methyl-4-phenylpyridinium ion (MPP+) on the release of DA in rat striatum by the in vivo microdialysis technique. For this study, we made a suitable microdialysis probe from a 22-G needle, microliter pipette tip, silica tube and polyethylene tube. Such a repairable microdialysis probe can be easily made from readily available and inexpensive materials. DA release, as determined by the 3-methoxytyramine level, was dose-dependently increased by MPP+ (1-10 mM). Only the presence of a 1 mM concentration of MPP+ in the dialysate significantly decreased the level of the DA metabolite DOPAC, while administration of higher MPP+ concentrations resulted in no significant change.


[Nursing research issues and trends: views from Korea]. The purposes of study was: 1. To identify the direction and scope of research activities in Korean Nursing. 2. To discuss the unique problems present in Korea that warrant nursing research. 3. To delineate the factors that facilitate and/or hinder nursing research in Korea. This study was conducted at six colleges of nursing in Korea. The schools which were selected had doctoral programs at the time, the data were collected in 1990. Four of the schools were located in the metropolitan area of the capital city, Seoul, and two were in two other cities similar in size. The total population of the study was 283 nurses. The instrument for the research was the English version of Research Profile Questionnaire which was translated into Korean by the researchers and was validated in its translation by two professors. A pretest procedure was done before the data collection process. Of the population of 283,210 subjects received the questionnaire and 150 subjects responded (71.4%). Excluding incomplete questionnaires, 141 questionnaires were utilized for data analysis. Data were analyzed using descriptive statistics. Responses to open-ended questions were content analyzed for themes and categories. Results of the study were as follows: Respondents currently involved in nursing research numbered 108 (76.6%), but 33 (23.4%) did not have any research experience. The inexperienced respondents tended to be younger than the experienced subjects and most (60.6%) were employed in hospitals, while 82.4 percent of the experienced nurses were employed in nursing schools. Among the respondents with research experience, 68.5 percent were involved in one to three projects and 31.5 percent were engaged in four or more projects. The experienced nurses indicated that nursing research in Korea is active. On the other hand, the responses of the inexperienced were that nursing research is not active. The most frequently selected research subjects were patients (76.9%, 83 respondents) followed by nurses, healthy persons and nursing students. The relatively high percentage of healthy persons as study subjects, could be explained as a concern of nurses for healthy persons as well as for ill patients. The aforementioned literature review showed a dramatic change in the kinds of study subjects; approximately 33 percent were patients but 25 percent were healthy subjects of various ages. The hospital was the prevailing research setting (67.6%) but at the same time various community settings were used. This is a changing phenomena in nursing research of Korea. Current research designed to build on previous studies amounted to 75 percent; about 39.8 percent were theory and hypothesis generated.(ABSTRACT TRUNCATED AT 400 WORDS)


[Study on the families' participation need for women in labor]. This study was done to suggest basic modifications in the present situation for the family of women in labour which is a separation management method. The study design was a descriptive study. The number of the subjects were 80. They were husbands, mothers in law, and mothers of women in labour who were full term and for whom there were no complications, either for the mother or the fetus. Data collection was done with a structured questionnaire which was analyzed using frequencies. The results were as follows, 1. Most of the subjects (95.0%) wanted to participate in the labour process. 2. The subjects wanted to support the women in labour by way of encouraging (95.0%), consoling (95.0%), listening to (75.0%), praying with (68.8%), hand holding (97.5%), stroking (63.8%), helping with respiration control (50.0%), maintaining relaxation (46.3%), changing position (58.8%), and illustration (58.8%). 3. The subjects answered that they expected their participation to have the effect of an easier labour course (52.5%), security for the women in labour (95.0%), and providing a better relationship between the women in labour (66.3%) and the new baby (55.0%). 4. The priority of the response as to who is the best supporter was husband, and mother of the women in labour in that order. It can be concluded that nurses maintained a management method which ignored the needs of the families of women in labour. If given consideration is to be given to these subjects, future programs should initiate ways to let the families participate in the labour process.


Identification of free and esterified hydroxyoctadecadienoates (HODEs) and linoleate-hydroxylating pathway in the epidermis of hairless mice. Epidermal homogenates of hairless mice contained a large amount of lipid material showing a single peak on reverse phase (RP)-high pressure liquid chromatography (HPLC) with a maximum absorbance of 234 nm, which was different in retention time from arachidonate metabolites such as 12-HETE, 15-HETE and 5-HETE. The production of this material was dependent on exogenous linoleate concentration, protein concentration and buffer pH. This material was identified to be a mixture of 13-HODE and 9-HODE on the basis of UV absorbance spectra, retention times on RP-HPLC, straight phase (SP)-HPLC, gas chromatography-mass spectrometry (GC/MS) and mass spectra obtained. As assessed by SP-HPLC after saponification, these two HODEs were found to exist primarily in esterified forms in the skin. Neither substance was produced following heat denaturation of the homogenate. These results indicate that 13- and 9-HODEs are produced from linoleate enzymatically at physiologically relevant levels in the epidermis of hairless mice. Thus, it is possible that these two materials may play some important role in pathophysiology of the skin.


A retrospective study of resected gastric cancers. From 1976 to 1989, a total of 1303 patients with gastric cancers underwent gastrectomies in the First Department of Surgery, Kurume University Hospital. Of these, 358 (27.5%) were total gastrectomies, 84 (6.4%) were proximal gastrectomies and 825 (63.1%) were distal gastrectomies. The 5-year survival rate was 44.8% after the total gastrectomies, 38.9% after the proximal and 72.4% after the distal gastrectomies. The 5-year survival rate was 86.2% with the absolute curative resection, 36.3% with the relative curative resection, 29.3% with the relative non-curative resection and 9.4% with the absolute non-curative resection. Macroscopically, the 5-year survival rate was 95.1% for type 0 (early cancers), 61.3% for Borrmann type 1, 58.8% for Borrmann type 2, 37.5% for Borrmann type 3 and 16.5% for Borrmann type 4. According to the pathological cancer stage, the 5-year survival rate was 94.8% for stage I, 79.3% for stage II, 49.2% for stage III and only 11.3% for stage IV.


Mandibular angloplasty.

Mandibular angloplasty. Bulging of the mandibular angle is considered to be unattractive in the Orient since it gives the face a quadrangular and muscular appearance. In spite of its muscular origin, surgery should be aimed toward bony reduction or osteoplasty and supplemental myotomy. An intraoral approach was utilized with an oscillating saw to resect a predetermined segment of bone (mandibular angloplasty). In 2 patients with a prominent bilateral mandibular angle, only the bony angle was resected. The improvement of facial esthetics was subtle, and the acceptance and satisfaction of the patients were very good. A review of the literature is included with comments on the diagnosis and treatment of benign masseteric hypertrophy.


Incidentally identified multiple low-intensity areas on T2-weighted images by MR imaging. Multiple small lesions of low intensity on T2-weighted images identified by MR imaging were observed in four patients. There were no definite associations between the patients' clinical symptoms and the lesions. MR imaging showed multiple, small areas with slightly high and/or low-intensities on T1-weighted images, and low intensities on T2-weighted images. IN two patients these low intensity areas were increased in size with field echo images. These MR studies indicate that multiple ruptures and/or hemorrhagic infarctions of microaneurysms may occur in the brain without any clinical manifestations.


Preoperative prediction of mortality following surgery for esophageal cancer. Ninety-five patients with thoracic esophageal cancer who had undergone radical esophagectomies through right thoracotomies from 1986 to 1989 were statistically analyzed semi-quantitatively to identify the risk factors predicting "operative (within 45 days of operation) or hospital death." Age, pulmonary function (%VC or %FEV1.0), cardiac function (EKG or Master test), renal function (Ccr), hepatic function (R15'ICG), diabetes mellitus (75 OGTT), extent of tumor invasion to the adventitia, and the type of operative procedure were each scored according to severity; 0 (no risk), 1, 2, or 3 (high risk). Patients with no severe postoperative complications had an accumulated score of less than 8 and comprised Group I, while those suffering an an "operative death" had a total score of 8 or more, and comprised Group II. Group III included those suffering a "hospital death." There was a significant difference between Group I and Group II (p < 0.005), but not between Group I and Group III. "Operative deaths" could be preoperatively predicted from the risk factors. However, "hospital deaths" could not be predicted, since they resulted mainly from recurrences of the cancer. In cases with scores of 8 or more the operative procedure should be changed to a simpler one for an improved prognosis.


Cervico-thoraco-abdominal (3-field) lymph node dissection for carcinoma in the thoracic esophagus. The efficacy of an extended radical lymph node dissection for carcinoma in the thoracic esophagus is controversial. Results of a multivariate analysis using clinical data from 127 cases collected from 1982 to 1988 are reported. Twenty-seven of these patients underwent an extended radical (cervico-thoraco-abdominal: 3 fields) lymph node dissection which was recently developed in Japan, while others underwent a standard (thoraco-abdominal: 2 fields) lymph node dissection. They all had a locally-curative resection of the tumor through a right thoracotomy. In this study, 13 factors commonly affecting prognosis were examined: sex, age, cancer location, tumor length, radiographic type, depth of invasion, lymph node metastasis, tumor differentiation, postoperative radiotherapy, chemotherapy, operative risk, postoperative complications, and 3-field or 2-field dissection. Based on the survival-rate curves using Kaplan-Meier's statistics, the 3-field dissection was superior to the 2-field dissection. Moreover, when other prognostic factors were adjusted using Cox's proportional hazards general linear model, the same result was obtained from survival-rate curves. From this analysis, it can be concluded that a 3-field dissection is a better approach for management of carcinoma in the thoracic esophagus.


Preoperative radiation for carcinoma of the thoracic esophagus involving adjacent organs--a comparative and multivariate analysis of prognosis. Controversy remains over the comparative efficacy and subsequent prognosis for preoperative radiation for carcinoma of the esophagus involving the trachea, bronchus, and/or aorta. Results of a multi-variate analysis are reported using clinical data from 57 cases from 1981 to 1987. Based on both the survival-rate curves using the Kaplan-Meier method and the adjusted survival-rate curves using Cox's proportional hazards linear model, there was no significant difference in prognosis between patients who received preoperative radiation and those who did not. This analysis indicates that preoperative radiation at doses of 30Gy produces no clinical advantage and therefore is not the best treatment for carcinoma of the esophagus involving these adjacent organs.


Questionable resection for carcinoma of the esophagus involving the trachea, bronchus and/or aorta--a comparative and multivariate analysis. Controversy remains over the comparative efficacy and subsequent prognosis of resections for carcinomas of the esophagus involving the trachea, bronchus, and/or aorta. Results of a multi-variate analysis are reported using clinical data from 103 cases from 1981 to 1987. Based on the survival-rate curves according to the Kaplan-Meier method, resection was superior to non-resection. However, when other prognostic factors were adjusted using Cox's proportional hazards linear model, there was no significant difference between the resection and non-resection groups. This analysis indicates that esophagectomy is not necessarily the best approach for carcinoma of the esophagus involving these adjacent organs, although it must be remembered that resection provides excellent palliation.


Sclerotic fibromas of the skin--reports of two cases and a review of the literature in Japan. Two cases of sclerotic fibromas of the skin are presented. Clinical and light-microscopic findings are also reviewed from 8 sclerotic fibromas of the skin arising in other Japanese patients. The patients in this series had no manifestations of Cowden's disease.


Intraperitoneal transplantation of ascitic cancer cells from a 7,12-dimethylbenz[a]anthracene (DMBA)-induced ovarian cancer. Intra-abdominal implantation of 7,12 dimethylbenz[a]anthracene (DMBA)-induced rat ovarian cancer tissue produces intraperitoneal carcinomatosis with a high incidence. The peritoneal carcinoma produces malignant ascites in 62% of the donor rats. The ascites is bloody in appearance and includes an average of 1.2 x 10(6) cancer cells/ml. To observe the transplantability of the ascites, 0.1 ml of a condensed ascites with 4 x 10(6) cancer cells was injected into the abdominal cavity of 118 infant rats that were 2 to 4 days old. In 103 rats (87%), the ascitic cells were successfully transplanted. Twelve rats were sacrificed each week from the 2nd to the 6th week following the inoculation. The omentum was the first site at which the metastastic tumor appeared following the inoculation. Then the tumor disseminated throughout the intraperitoneal cavity and produced bloody ascites by the 3rd week. Eighty-four rats were observed to determine the survival, and it was 34 +/- 10 days. Cytologically the ascites had clusters of tumor cells resembling bunches of grapes. The ultrastructure of the ascitic cells was globular shaped with many microvilli and epithelial attachments. The histology of the developed tumor was that of an adenocarcinoma. Due to morphological similarity with advanced human ovarian cancer and the high reproducibility, this experimental system could be a feasible model for human ovarian cancer, especially the type which produces malignant ascites.


Doppler ultrasonographic assessment of fetal renal artery blood flow velocity waveforms in intrauterine growth retarded fetuses. Thirty-two blood flow velocity waveforms of the fetal renal artery, umbilical artery and fetal middle cerebral artery were recorded by a pulsed Doppler ultrasound from 28 to 38 gestational weeks in 32 intrauterine growth-retarded (IUGR) fetuses without structural defects. The nonstress test (NST) was performed on the day of pulsed Doppler ultrasonographic examination to assess fetal well-being. Of the 32 fetuses, the pulsatility index (PI: peak systolic velocity minus end diastolic velocity over mean velocity) values in the fetal renal artery were in the normal range in 26 measurements (81.3%), high in 2 (6.3%) and low in 4 (12.5%). The resistance index (RI: peak systolic velocity minus end diastolic velocity over peak systolic velocity) values in the umbilical artery and fetal middle cerebral artery were determined simultaneously in all the patients examined. Of the 12 fetuses with high RI values in the umbilical artery and low RI values in the fetal middle cerebral artery, the PI values in the fetal renal artery were within the normal range in 11 measurements (91.7%) and high in 1 (8.3%). Of the 9 fetuses with loss of fetal heart rate baseline variability in NST, the PI values in the fetal renal artery were within the normal range in 7 measurements (77.8%), high in 1 (11.1%) and low in 1 (11.1%). These data suggest that fetal renal blood flow may not change under the condition of chronic hypoxic state, although the NST shows fetal distress and the pulsed Doppler ultrasound reveals a brain sparing effect in the fetal middle cerebral artery. It is hypothesized that the fetal renal blood flow is controlled by an autoregulation mechanism for oxygen delivery presumably located in the renal artery.


[A study of psychiatric patients perceived effect and expectancy of activity therapy]. The intent of this descriptive study is to investigate the patients perceived effect and expectance of activity therapy. The subjects for this study were 56 patients from the psychiatric ward in Severance Hospital. The data were collected during the period from June 1, 1991 to January 18, 1992. The effect and expectance of the activity therapy was measured using a questionnaire developed by this study's investigators. The date were analyzed by descriptive statistics, t-test and one-way ANOVA, using the SPSS program. The results of this study can be summarized as following; 1. For motivation for the activity therapy, the response range was from 64.3% to 89.3%, that is, it showed a relatively positive response. 2. For the degree of improvement according to the nurse's method in the activity therapy, it was shown that the nurses need professional skill and meeting after activity therapy. 3. For the relevance of the nurse in the activity therapy, 90% of the subjects had a positive answer for all of the activity therapy except the painting therapy. 4. For the perceived effect of the activity therapy, the following results were obtained. 1) 92% of the subjects had a positive response to the dance therapy, that is-I am vigorous physically. 2) 90% of the subjects had a positive response to the reading therapy, that is-I acquire good ideas and instruction. 3) 98.1% of the subjects had a positive response to the recreation therapy, that is-I am joyful. 4) 88.9% of the subjects had a positive response to the writing therapy, that is-I am interested and become acquainted with other patients. 5) 86.8% of the subjects had a positive response to the occupation therapy, that is-I am happy when I work. 6) 92.6% of the subjects had a positive response to the painting therapy, that is-I can express myself in painting. 7) 87.3% of the subjects had a positive response to the music therapy, that is-I am comforted. 5. For the expectance related to the activity therapy, 97.1% of the subjects had the most positive response to the music therapy which is a pleasant comfortable time. From the above-mentioned findings, it is suggested that psychiatric nurses need to development systematic and professional group activity therapy, and know the patient premorbid hobbies, interests and occupations.


[A study of home care needs of patients at discharge and effects of home care--centered on patients discharged from a rural general hospital]. The study was carried out at W. hospital, an affiliated hospital of Y university, involved a total of 163 patients who were discharged from the hospital between May 1990 and March 1991. Data collection was twice, just prior to discharge and a minimum of three months post discharge. Thirty patients who lived within a hour travel time of the hospital received home care during the three months post discharge. Nursing diagnoses and nursing interventions for these patients were analyzed in this study. The results of the study are summarized as follows: 1. Discharge needs for the subjects of the study were analyzed using Gordon's eleven functional categories and it was found that 48.3% of the total sample had identified nursing needs. Of these, the needs most frequently identified were in the categories of sexuality, 79.3%, health perception, 68.2% self concept, 62.5%, and sleep and rest 62.5%. Looking at the nursing diagnosis that were made for the 30 patients receiving home care, the following diagnoses were the most frequently given; alteration in sexual pattern 79.3%, alterations in health maintenance, 72.6%, alteration in comfort, 68.0%, depression, 64.0%, noncompliance with diet therapy, 63.7%, alteration in self concept, 55.6%, and alteration in sleep pattern, 53%. 2. In looking at the effects of home nursing care as demonstrated by changes in the functional categories over the three month period, it was found that of the 11 functional categories, the need level for health perception, nutrition, activity and self concept decreased slightly over the three month period. On the average sleep patterns improved, but restfulness was slightly less and bowel elimination patterns improved but satisfaction with urinary elimination was slightly less. On the other hand, role enactment, sexuality, stress management and spirituality decreased slightly. The only results that were statistically significant at the 0.05 level were improvement in digestion and decrease in pain. No statistically significant changes were found in ability related to ADL, the total ADL score at discharge was 19.78 +/- 8.23, and after 3 months 19.01 +/- 8.12. Considering that a majority of the patients were over 60 years of age and that many had brain or spinal cord injuries, the fact that their ADL ability did not deteriorate after discharge can be interpreted as related to a positive impact by the home health care nurses. Similarly there was a slight but not statistically significant decrease in the quality of life scores between the two test times (147.83 at discharge and 143.02 at the three month period).(ABSTRACT TRUNCATED AT 400 WORDS)


6R instrumented spatial linkages for anatomical joint motion measurement--Part 2: Calibration. The six-revolute-joint instrumented spatial linkage (6R ISL) is often the measurement system of choice for monitoring motion of anatomical joints. However, due to tolerances of the linkage parameters, the system may not be as accurate as desired. A calibration algorithm and associated calibration device have been developed to refine the initial measurements of the ISL's mechanical and electrical parameters so that the measurement of six-degree-of-freedom motion will be most accurate within the workspace of the anatomical joint. The algorithm adjusts the magnitudes of selected linkage parameters to reduce the squared differences between the six known and calculated anatomical position parameters at all the calibration positions. Weighting is permitted so as to obtain a linkage parameter set that is specialized for measuring certain anatomical position parameters. Output of the algorithm includes estimates of the measuring system accuracy. For a particular knee-motion-measuring ISL and calibration device, several interdependent design parameter relationships have been identified. These interdependent relationships are due to the configuration of the ISL and calibration device, the number of calibration positions, and the limited resolution of the devices that monitor the position of the linkage joints. It is shown that if interdependence is not eliminated, then the resulting ISL parameter set will not be accurate in measuring motion outside of the calibration positions, even though these positions are within the ISL workspace.


Finite element stress analysis of a push-out test. Part 1: Fixed interface using stress compatible elements. In this first part of a two-part paper, interelement stress compatible finite elements are developed and used to perform the stress analysis of a push-out test with a fixed interface. In the formulation, the required continuity of some of the stresses along either a specific interface or all interelement interfaces is enforced by a penalty procedure. The model is axisymmetric and consists of two cylinders attached to each other through the interface. Various relative material properties and boundary conditions are simulated in order to examine their effects on the interface stresses. Both loadings of axial compression force and axial torque are considered. The predicted results exhibit identical interelement stresses and displacements even when highly dissimilar materials are used. They also exhibit a complex state of interface stresses which depend on the geometry, material arrangement, boundary conditions, and loading. The variation of the shear stress is often highly nonuniform and the radial normal stresses are likely to be large. The present results, therefore, disagree with the common assumptions made in the pull-out tests in the orthopaedic applications. Finally, stress analysis of a number of possible testing configurations could lead to the design of an optimal pull-out test which maximizes the usefulness of the measured results in terms of the interface bond strength and factors affecting it.


Failure analysis of a beam-column under oblique-eccentric loading: potential failure surfaces for cervical spine trauma. For a cantilever beam-column with one end built-in and the free end subjected to an oblique-eccentric arbitrary concentrated force, general formulas to produce failure were derived. The original generalized uniform solution to the oblique-eccentric buckling problem was obtained. The Secant formula and Euler's formula were proved to be specific cases in this general solution. The load ratio, F/aE, was derived as functions of the force acting direction, alpha, the slenderness ratio, L/r, as well as the eccentricity ratio, ec/r2. Material and buckling failures aspects were combined in a uniform structural failure analysis. Safe regions for the load ratio, F/aE, were visualized in the three-dimensional (F/aE)-alpha-(L/r) space with the eccentricity ratios, ec/r2, as a parameter. The column failure factor, kL, was shown to be a key index controlling both aspects of failure as well as the orientation of the second stiffest region. The angle alpha E = tan-1 (2L/pi e) for kL = pi/2 is the singular point for both strength and buckling failure, and alpha II = tan-1 (2L/3e) for KL = 0 is the upper bound of the second stiffest region. The feasible domain of the second stiffest region is bounded by alpha E and alpha II both of which are only functions of geometrical properties. The implications of these analyses for the experimental validation of cervical spine trauma are discussed.


An evolutionary Wolff's law for trabecular architecture. A continuum model is proposed to describe the temporal evolution of both the density changes and the reorientation of the trabecular architecture given the applied stress state in the bone and certain material parameters of the bone. The data upon which the proposed model is to be based consist of experimentally determined remodeling rate coefficients and quantitative stereological and anisotropic elastic constant measurements of cancellous bone. The model shows that the system of differential equations governing the temporal changes in architecture is necessarily nonlinear. This nonlinearity is fundamental in that it stems from the fact that, during remodeling, the relationship between stress and strain is changing as the stress and strain variables themselves are changing. In order to preserve the remodeling property of the model, terms that are of the order strain times the changes in density and/or microstructural properties must be retained. If these terms were dropped, there would be no feedback mechanism for architectural adaptation and no adaptation of the trabecular architecture. There is, therefore, no linearized version of the model of the temporal evolution of trabecular architecture. An application of the model is illustrated by an example problem in which the temporal evolution of homogeneous trabecular architecture is predicted. A limitation of the proposed continuum model is the length scale below which it cannot be applied. The model cannot be applied in regions of cancellous bone where the trabecular bone architecture is relatively inhomogeneous or at a bone-implant interface.


A composite micromechanical model for connective tissues: Part I--Theory. A micromechanical model has been developed to study and predict the mechanical behavior of fibrous soft tissues. The model uses the theorems of least work and minimum potential energy to predict upper and lower bounds on material behavior based on the structure and properties of tissue components. The basic model consists of a composite of crimped collagen fibers embedded in an elastic glycosaminoglycan matrix. Upper and lower bound aggregation rules predict composite material behavior under the assumptions of uniform strain and uniform stress, respectively. Input parameters consist of the component material properties and the geometric configuration of the fibers. The model may be applied to a variety of connective tissue structures and is valuable in giving insight into material behavior and the nature of interactions between tissue components in various structures. Application of the model to rat tail tendon and cat knee joint capsule is described in a companion paper [2].


A composite micromechanical model for connective tissues: Part II--Application to rat tail tendon and joint capsule. A micromechanical model of fibrous soft tissue has been developed which predicts upper and lower bounds on mechanical properties based on the structure and properties of tissue components by Ault and Hoffman [3, 4]. In this paper, two types of biological tissue are modeled and the results compared to experimental test data. The highly organized structure of rat tail tendon is modeled using the upper bound aggregation rule which predicts uniform strain behavior in the composite material. This model fits the experimental data and results in a correlation coefficient of 0.98. Applied to cat knee joint capsule, the lower bound aggregation rule of the model correlates with the data and predicts uniform stress within this more loosely organized tissue structure. These studies show that the nature of the interactions between the components in tissue differs depending upon its structure and that the biomechanical model is capable of analyzing such differences in structure.


Secondary flow in the human common carotid artery imaged by MR angiography. The blood flow in arteries affects both the biology of the vessels and the development of atherosclerosis. The flow is three-dimensional, unsteady, and difficult to measure or to model computationally. We have used phase-shift-based magnetic resonance angiography to image and measure the flow in the common carotid arteries of a healthy human subject. There was curvature of the vessels and thin-slice dynamic flow imaging showed evidence of the presence of secondary motions. Flexing the cervical spine straightened the vessels and reduced the asymmetry of the flow.