HLA-DRB1 alleles and beta 2 glycoprotein I-dependent anticardiolipin antibodies in Japanese patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the association of HLA DRB1 alleles with beta 2 glycoprotein I (beta 2 GPI)-dependent anticardiolipin antibodies (aCL) in Japanese patients with systemic lupus erythematosus (SLE). METHODS: One hundred and forty-five Japanese patients with SLE were studied. beta 2 GPI-dependent aCL was measured by enzyme-linked immunosorbent assays. DNA typing of the DRB1 alleles was performed by the polymerase chain reaction sequence specific oligonucleotide probe method. RESULTS: beta 2 GPI-dependent aCL was positive in 29 (20.0%) out of 145 SLE patients. SLE patients with beta 2 GPI-dependent aCL had a significantly higher frequency or one or more of the clinical manifestations assumed to be associated with aCL, compared to those without beta 2 GPI-dependent aCL (p < 0.05). The frequency of DRB1*0901 was lower in SLE patients than in healthy subjects. SLE patients with beta 2 GPI-dependent aCL were significantly associated with DRB1*0901 as compared to those without beta 2 GPI-dependent aCL (41.4% vs 15.5%, p < 0.005, R.R. = 3.8), although the corrected P value was not significant. CONCLUSION: A possible association of DRB1*0901 with Japanese SLE patients with beta 2 GPI-dependent aCL was found. This association indicates an association between the disease and the HLA-DR53 (DRB4)-bearing haplotypes in different ethnic groups.

Modeling of cardiac muscle contraction based on the cross-bridge mechanism.

A mathematical model was developed for the cardiac muscle contraction, assuming that the attachment and detachment cycle of the cross-bridge is activated by the internal calcium concentration and the rate constant of the cycle depends on the sliding velocity of myofilaments. The inputs of the model are the rates of calcium release and uptake, while the output is the tension curve of the muscle. The variables are factored into a series of realizable functions and most constants were determined from the dynamic constants for the tetanic contraction of frog ventricular muscle at 20 degrees C. Using this model, the calcium transient curve as well as the change in the number of cross-bridges in each state of the cycle during a given experimental twitch tension curve was calculated with a PDP 11/60 computer, by selecting the input parameters so that the output curve fit the experimental curve. When the twitch tension was increased by increasing initial muscle length, the rate of calcium release increased and that of uptake decreased. At higher external calcium concentrations, the similar changes in the input parameters were observed. In the presence of 5 X 10(-6) g/ml adrenaline the duration of activation was markedly prolonged, while the rates of calcium release and uptake show little change.

Innovation in nursing education: development of computer-assisted thinking.

In order to enhance students' active thinking, faculty members at International University of Health and Welfare developed the CAT (Computer Assisted Thinking) program. The CAT program is different from CAI (Computer Assisted Instruction), which mainly asks users to choose correct answers. Instead, the CAT program asks users to type in short sentences. There are two functions in the CAT program: one is to keep the students' action log each time they use the program and the other is to serve as medical dictionary. An analysis of the action log revealed that the students demonstrated little skill in inferential thinking. Their observations were very concrete. In order to help the students to develop their abstract thinking skills, we need to review our curriculum.

[The empirical risk of retinitis pigmentosa in Japan].

The empirical risk of hereditary retinitis pigmentosa (RP), was studied based on a survey of the data from 378 families with RP who were seen in Juntendo University hospital from 1980 to 1988. If the cases have had affected sibling, the empirical risk is 19% for the other siblings, and 29% if they have parental consanguinity. Moreover the risk for male siblings is about 1.7 times higher than for female siblings. The prevalence in the general population of carriers with autosomal recessive hereditary RP was calculated to be about 0.8 to 1.7 in 100 persons. If a hereditary RP case marries a normal and unrelated partner, the risk is 0.4-0.9% for their child. If a case has many affected relatives (parents, grandparents, uncles or aunt etc), the risk is 24% for a son, and 30% for a daughter. Some normal persons among autosomal dominant families with incomplete penetrance are suspected to be carriers. The rate of penetration of the autosomal dominant gene was estimated to be 0.54. Therefore, the risk is 8.6% for the children of such persons. If the carriers are among X-linked families, the risk is 36% for their son. The risk is 1% or more for children of sporadic cases.

[Statistical analysis of Marfan's syndrome].

To evaluate the ocular complications of Marfan's syndrome which cause severe visual disturbance, we retrospectively investigated 104 patients (208 eyes) with Marfan's syndrome. Dislocation of the lens, the most frequent ocular manifestation, was detected in 151 eyes (72.6%). There were 33 eyes with a visual acuity 0.1 or less. In this group, we found retinal detachment in 12 eyes (36.4%) and glaucoma in 5 eyes (15.2%) as the causes of visual disturbance. Among 17 eyes with retinal detachment, 5 eyes (29.4%) had horizontally dislocated lens. On the other hand. The lens dislocation in a downward direction was found in 5 (22.7%) of 22 eyes with glaucoma. No lens dislocation in an upward direction was found in eyes with glaucoma. The incidence of retinal detachment in aphakic eyes (5/31, 16.1%) was higher than that in the phakic group (16/177, 9.0%). In only 2 (3.6%) of 56 eyes, did the lens dislocation become markedly worse during the observation period. From these data, we re-confirmed that retinal detachment and glaucoma are the most important ocular complications of Marfan's syndrome leading to severe visual disturbance. The decision to operate on the dislocated lens should be made cautiously.

Studies on the outcome of lupus nephritis according to long-term treatment employing different modes of immunotherapy.

The outcome of long-term treatment of lupus nephritis under different immunotherapies, together with the factors affecting the outcome of lupus nephritis, was studied. A total of 212 lupus nephritis patients were classified into 5 groups according to their different modes of treatment: (1) initial dose of prednisolone (PSL) below 39 mg/day, (2) initial dose of PSL above 40 mg/day, (3) pulse therapy and steroids, (4) steroids and immunosuppressants, and (5) combination therapy of plasmapheresis with other therapies. The outcome of lupus nephritis was evaluated into 5 grades. As a result, the complete remission rate of lupus nephritis was 9.4%. The 5-year survival rates increased with all modes of treatment. However, it was impossible to identify which mode of therapy could bring about the highest rate of remission. Decreases in extrarenal involvement and low complement levels were observed together with increases in IgM anti-DNA antibodies among the lupus nephritis patients with remission.

Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis.

BACKGROUND: It is thought that overexpression of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) might compromise patient survival, presumably by promoting tumour growth by an autocrine mechanism. However, conflicting results have been reported from various laboratories, and the clinical importance of EGFR overexpression remains unsettled. METHODS: A meta-analysis of previous studies was performed to quantitatively review the effects of EGFR overexpression on survival in patients with NSCLC using a DerSimonian-Laird random effects model. Eighteen studies including 2972 patients were subjected to final analysis. RESULTS: Overall, positivity for EGFR overexpression differed between histological types: 39% in adenocarcinomas, 58% in squamous cell carcinomas, 38% in large cell carcinomas, and 32% in cancers in a miscellaneous category (p<0.0001). The combined hazard ratio (HR) was 1.14 (95% CI 0.97 to 1.34; p = 0.103), indicating that EGFR overexpression has no significant impact on survival. When only the 15 immunohistochemistry based studies were considered, the combined HR was 1.08 (95% CI 0.92 to 1.28; p = 0.356), again suggesting that EGFR overexpression has no impact on survival. Heterogeneity testing indicated that there was heterogeneity between studies but publication bias was absent, which suggests that the summary statistics obtained may approximate the actual average. CONCLUSIONS: EGFR overexpression was not associated with poorer survival in patients with NSCLC. Specific mutations of the EGFR gene will need further study in terms of survival implications.

Survival following lobectomy vs limited resection for stage I lung cancer: a meta-analysis.

Extent of resection needed to treat lung cancer has long been an issue. The sole randomised controlled trial, reported by the Lung Cancer Study Group, advised against limited resection as standard surgery even for small peripheral non-small-cell lung cancers (< or =3 cm), because of frequent local recurrences. Elsewhere, conflicting results have been reported from different institutions. We therefore conducted a meta-analysis of reported studies to compare survival of stage I patients between limited resection and standard lobectomy. A MEDLINE web search for computer-archived bibliographic data yielded 14 articles suitable for analysis. Combined survival differences (survival rate with lobectomy minus that with limited resection) at 1, 3, and 5 years after resection according to the DerSimonian-Laird random effects model were 0.7% (95% CI, -0.8 to 2.1; P=0.3659), 1.9% (95% CI, -3.7 to 7.4; P=0.5088), and 3.6% (95% CI, -0.4 to 10.5; P=0.3603), respectively. None of these survival differences were significant, indicating that survival after limited resection for stage I lung cancer was comparable to that after lobectomy. However, since interstudy heterogeneity was detected, caution is required in interpretation of the results.

A sequential diagnostic model for medical questioning.

A medical interview is a very important part of medical treatment since it is conducted when a patient is first admitted to a hospital and treatment is decided afterwards. However, these interviews are not always carried out in sufficient detail because physicians have very heavy work-loads. The development of automated medical questioning equipment which tabulates the answers to questions into a form easily understood by physicians, which enumerates data on doubtful diseases and which indicates pertinent medical examinations may come to the aid of patients and physicians. This paper presents a new diagnostic theory for the design of automated medical questioning equipment. Diagnostic theories can be classified into batch and sequential theories; the authors have investigated the sequential one, because decisions are made using minimal data. The techniques supporting this theory are multi-class recognition systems based on independently designed dual-class recognition systems and Wald's Sequential Probability Ratio Test. To discuss the properties inherent in the present theory, classification of three pattern classes was made. These were normal, hypertension and myocardial infarction classes of patients. The mean error probability of classification was found to be 3.08%.

Evaluation of a new method for identification of Cryptococcus neoformans which uses serologic tests aided by selected biological tests.

A new method for identifying Cryptococcus neoformans isolates and their serotypes by the slide agglutination test using five kinds of factor sera, with the aid of nitrate reduction, phenol oxidase, and growth at 37 degrees C tests was evaluated by using 36 reference strains and 75 clinical isolates of C. neoformans. The results showed that the reference strains were identified exactly as they were labeled, and clinical isolates were identified as C. neoformans serotypes A, D, and AD. C. neoformans could be distinguished from other Cryptococcus species that cross-reacted with factor sera by their ability to grow at 37 degrees C. These results indicate that the slide agglutination test combined the use of factor sera for isolates which grow at 37 degrees C is a useful method for identification of C. neoformans and their serotypes and that the nitrate reduction test (negative in 100% of the isolates) and the phenol oxidase test (positive in approximately 95% of the isolates) can be used to confirm that the species is C. neoformans.

[Studies on clinical subsets and severity of systemic lupus erythematosus based on a 1987 questionnaire conducted in Japan--clinical analysis of the outcome and treatments in clinical subsets].

A 1987 questionnaire sponsored by the Health and Welfare Ministry concerning the clinical subsets and severity of systemic lupus erythematosus (SLE) was distributed to 93 medial facilities. A clinical analysis of the outcome and treatments was accomplished on one thousand six hundred and fourteen SLE patients fulfilling ARA criteria. The outcome was evaluated into 6 categories, namely; complete remission, incomplete remission, no change, gradual worsening, rapid worsening and unknown. Treatments included (1) anti-inflammatory drugs, (2) initial dose of prednisolone (PSL) below 29 mg/day, (3) initial dose of PSL from 30 to 59 mg/day, (4) initial dose of PSL above 60 mg/day, (5) pulse therapy, (6) immunosuppressants, (7) plasmapheresis, and (8) hemodialysis. Statistical significances were determined with ridit analysis. The severity of the disease for 1,614 SLE patients was evaluated by the judgement of each medical facility independently, separating it into 3 grades. As a result, 16.8% was evaluated as severe, 54.6% was evaluated as moderate, and 28.6% was evaluated as mild. Clinical subsets were divided into 3 categories according to the outcome; (1) those with high complete remission rates (serositis, convulsion, oral ulcers, unconsciousness, hemolytic anemia and so on), (2) those with high incomplete remission rates (lupus nephritis, digital gangrene, hypertension, peripheral neuropathy, erythema, Raynaud's phenomenon and so on), and (3) those with high rates of no change or worsening (aseptic bone necrosis, pulmonary hypertension, pneumonitis, chronic renal failure and so on). SLE patients with persistent proteinuria below 3.4 g/day, pulmonary hypertension, or pneumonitis treated with large doses of PSL such as an initial dose of PSL above 60 mg/day and/or pulse therapy had a significantly higher remission rate than those treated with small dosages of PSL. Hereafter, the establishment of modes of treatments for increasing the remission rates of intractable clinical subsets in highly desired.

[Studies on criteria for clinicopathological diagnosis of allergic granulomatous angiitis (AGA)].

Comparative studies in the evaluation of criteria for clinicopathological diagnosis of AGA which was proposed by Japanese Health and Welfare Ministry (JHWM) in 1988 and American College of Rheumatology (ACR) in 1990 were conducted. Twenty seven Japanese patients with AGA and 231 Japanese controlled patients with polyarteritis nodosa (PAN) and Wegener's granulomatosis (WG) were used as material patients who had been provided a second questionnaire in 1984 sponsored by the JHWM. As a result, the JHWM criteria was 85.2% in sensitivity and 96.5% in specificity, which was superior to the ACR criteria being 74.1% in sensitivity and 93.9% in specificity. These results were due to the low sensitivity and low accuracy in paranasal sinus abnormality and pulmonary infiltrates which were included in the ACR criteria. Furthermore, the JHWM criteria could be diagnosed as AGA using not only the histopathological findings but by the clinical symptoms alone. The controlled patients who were overdiagnosed as AGA using ACR criteria were thought to be included as patients with WG. On the other hand, the controlled patients who were overdiagnosed as AGA using JHWM criteria were thought to be included as patients with overlap syndrome of AGA and PAN. Accuracy of polyneuropathy, muscle weakness, melena and pretibial edema were over 60%, indicating that these clinical symptoms were available for vasculitis symptoms of the JHWM criteria.

Measurement of urinary lactoferrin as a marker of urinary tract infection.

The usefulness of the measurement of urinary lactoferrin (LF) released from polymorphonuclear leukocytes and of an immunochromatography test strip devised for measuring urinary LF for the simple and rapid diagnosis of urinary tract infections (UTI) was evaluated. Urine specimens were collected from apparently healthy persons and patients diagnosed as suffering from UTI. In the preliminary study, the LF concentrations in 121 normal specimens and 88 specimens from patients (60 with UTI) were quantified by an enzyme-linked immunosorbent assay. The LF concentration was 3,300.0 +/- 646.3 ng/ml (average +/- standard error of the mean) in the specimens from UTI patients, whereas it was 30.4 +/- 2.7 ng/ml and 60.3 +/- 14.9 ng/ml in the specimens from healthy persons and the patients without UTI, respectively. Based on these results, a 200-ng/ml LF concentration was chosen as the cutoff value for negativity. Each urine specimen was reexamined with the newly devised immunochromatography (IC) test strip to calculate the indices of efficacy. Based on the cutoff value, it was calculated that the sensitivity, specificity, and positive and negative predictive values of the IC test were 93.3, 89.3, 86.2, and 94.9%, respectively, compared with the results of the microscopic examination of the urine specimens for the presence of leukocytes. The respective indices for UTI were calculated as 95.0, 92.9, 89.7, and 96.6%. The tests were completed within 10 min. These results indicated that urine LF measurement with the IC test strip provides a useful tool for the simple and rapid diagnosis of UTI.

HLA antigens in Japanese patients with systemic lupus erythematosus.

To determine the association of HLA antigens with SLE and the clinical findings of the disease, HLA antigens were tested in 58 Japanese patients with SLE, who fulfilled the ARA diagnostic criteria, along with 97 normal controls. HLA class I and II antigens were typed serologically using the antisera provided by the 11th HLA Workshop. Among the HLA class II antigens, further DRB, DQ and DP alleles were defined by DNA typing using the PCR/SSOP method. There were significantly more SLE patients with HLA-B39, DRB1*1501, DRB5*0101 and DQB1*0602 than normal controls. This result suggested that the haplotype of HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 consists of the SLE-associated MHC markers in Japan. There were some positive and negative associations between the HLA antigens and clinical or serological findings in SLE. There is a possibility that some HLA alleles might be related to the clinical and/or serological subsets of SLE.