[Shigella flexneri strains having a new type antigen 89-141].

Two Shigella strains (89-141 and 89-11) isolated from the stool of patients returning from abroad (both from India) in Tokyo in 1989 showed an atypical serologic reaction of agglutination with only polyvalent antiserum to S. flexneri prepared commercially. These strains had the typical biochemical characteristics of S. flexneri and were biochemically identical. Both strains were positive for Serény test in guinea pig eye and cell-invasion test in HeLa cells. The strains also had virulence-plasmid encoding outer membrane proteins, indicating pathogenicity. The results of antigenic analyses showed that the strains were serologically identical to each other and gave significant cross-reactions with S. flexneri variant Y that has only group 3, 4 factor antigen. However, the results of reciprocal absorption tests showed that the O antigen of these strains was not identical to S. flexneri variant Y, and they were confirmed to have an additional type-specific antigen which is not included among the known S. flexneri type antigen I-VI or provisional type 88-893 which were proposed by us in 1992. Furthermore, one stock strain (TSH508) formally identified as S. flexneri variant X has this type antigen, suggesting that the new antigen can be classified into two subtypes by combination of group factor antigen. Strain 89-141 is designated as the test strain for this new type antigen of S. flexneri.


[Significance of normal oral flora, particularly group oral streptococci as defense mechanism against infection in healthy individuals (normal defense mechanism by oral Streptococcus group)].

The alpha-streptococci, consisted of normal oral flora mainly, with inhibitory activity against pathogenic microbes in healthy individuals was investigated by group A Streptococcus (indicator strain 6-22 nonmucoid T-12). Rate of alpha-streptococci with inhibitory activity against group A Streptococcus was increased as aging, and the rate in pre-school children was higher than that in school children. These results suggested that more than 90% of the tested alpha-streptococci with strong inhibitory activities (S. salivarius) against indicator strain had inhibitory activities against group A Streptococcus (mucoid T-6), H. influenzae, S. pneumoniae, group C Streptococcus, and from 40% to 70% of the tested strains had also inhibitory activities against other pathogens. As there were many strains of alpha-streptococci with inhibitory activities against pathogens, that usually detected in the upper respiratory infection, the problem on the strains in the future will explain significance of the defense mechanism against upper respiratory infection and this can be applied clinically.


[Distribution of Clostridium botulinum and Clostridium tetani in Okinawa Prefecture].

Soil samples from the sugar cane fields and muscovado samples from the manufacturing processes at sugar manufacturies in many parts of Okinawa Prefecture were collected, mainly in 1988 and 1989, and examined for Clostridium botulinum and Clostridium tetani. Of 290 soil samples 21 (7.2%) were positive for C. botulinum. Four (1.4%) and 17 (5.9%) contained types E and C respectively. C. botulinum type E was demonstrated in the North and South areas of Okinawa main island. Type A and B were not demonstrated from soil samples in Okinawa Prefecture. Of 53 samples of the manufacturing processes of muscovado 5 (9.4%) were positive for C. botulinum type C. Type A, B and E were not found from muscovado samples in Okinawa Prefecture. Of 290 soil samples 54 (18.6%) were positive for C. tetani. Among the 53 muscovado samples from the manufacturing processes of the sugar cane, 10 (18.9%) were positive for C. tetani.


[The first cholera case diagnosed early in the clinical laboratory by DNA probe method].

An alkaline-phosphatase-labelled synthetic oligonucleotide probe was applied to detect the structural gene of cholera enterotoxin (ctx). This DNA probe has a complementary base sequence to 30 base of the CT-A subunit. This method was, for the first time, applied to diagnosis of a diarrheal patient. The probe detected ctx rapidly and simply as compared with reversed passive latex agglutination (RPLA) and Beads-ELISA. The cfu minimal dose for detection with the probe was about 10(6-7)/ml. This method can be easily performed in any clinical laboratory because the procedure is safe, simple and rapid (it can be completed within about 3 hours).


[Human lymphocyte proliferative response and gamma-interferon production to Pneumocystis carinii antigen in vitro].

In vitro proliferative response and gamma-interferon (IFN-gamma) production to Pneumocystis carinii antigen were investigated in peripheral blood mononuclear cells (PBMC) from healthy volunteers and cord blood mononuclear cells (CBMC) from umbilical cords after delivery. Twenty three of 25 samples of PBMC had strong proliferative response, and 15 of 25 samples of PBMC produced IFN-gamma. In the samples showing strong proliferative response, CD4 lymphocytes expressed interleukin 2 receptors. None of the 3 CBMC samples had proliferative response nor production of IFN-gamma. When CD4 lymphocytes were depleted in PBMC, the proliferative response was markedly decreased and IFN-gamma production was abolished. In conclusion, the lymphocytes of healthy adults are activated and produce IFN-gamma by stimulation with P. carinii antigen, and these two response are both induced by CD4 lymphocytes.


Aerobic and anaerobic bacterial interactions in the development of anaerobic bacterial pneumonia.

The interactions between aerobic and anaerobic bacteria in the development of anaerobic bacterial pneumonia were studied by introducing Bacteroides fragilis and Escherichia coli alone or in combination into guinea pigs by tracheal infusion. The lung lesions induced by B. fragilis were mainly located near the pleura, unlike those induced by E. coli, and were accompanied by pneumonia, lung abscess, and pleuritis. The lung lesions produced by mixed infection with B. fragilis (10(9) cfu) and E. coli (10(7) cfu) were significantly more severe than those induced by either microbe alone, and the redox potentials at the foci of inflammation were markedly reduced (max: -330 mV). Analysis of lung lesions after treatment with aztreonam and clindamycin and neutrophil phagocytic activity suggested that E. coli was primarily responsible for the lung lesions and that B. fragilis promoted the accompanying inflammation, resulting in increased pathogenicity of the mixed infections.


[Rapid and direct detection of Mycobacterium tuberculosis complex and mycobacteria in sputum by advanced method, PCR].

We developed two PCR methods, which amplify bovine tuberculous MPB70 gene and mycobacterial 16S rRNA gene, for detection of tubercle bacilli and mycobacteria in sputum, respectively. Among 27 Mycobacterium species and 57 species of 30 genuses other than Mycobacterium, only M. tuberculosis (TB) complex, i.e., M. tuberculosis, M. bovis, M. africanum, M. microti showed DNA amplification by PCR for MPB70, and amplification of 16S rRNA gene were observed specific in Mycobacterium species. A combination of these PCR abilities were available to differentiate the TB complex and nontuberculous mycobacteria (NTM). We investigated the correlation between these methods and conventional methods with 311 sputa that were suspected mycobacteriosis. The PCR method could detect 12 cases of TB complex and 4 cases of NTM in 17 specimens, which were positive by conventional methods, but could not for one specimen. Among 294 specimens that were negative with conventional methods, the PCR method detected 13 and 8 cases of TB complex and NTM, respectively. These results were confirmed by commercial tuberculous specific DNA probe or investigation of the clinical background of the patients. On the other hand, 273 specimens showed negative result either PCR nor conventional methods. The PCR method did not detect tuberculous DNA in normal 197 sputa, which were not suspected mycobacteriosis. These results indicate that each one of these PCR methods is highly specific to TB complex or Mycobacterium species. We concluded that these PCR methods are useful and advanced methods for rapid and direct detection of tuberculosis and mycobacteriosis.


[A case of organizing pneumonia which had to be treated with steroids in the early phase of the disease against delayed resolution of severe pneumonia occurring even after antibiotic therapy].

A 58-year-old male was referred to our division because of antibiotic-resistant pneumonia. A chest X-ray film revealed severe pneumonia over the left lung field but laboratory data showed no leukocytosis. Transbronchial lung biopsy findings showed the evidence consistent with organizing pneumonia. One-month prednisolone therapy produced a disappearance of the pneumonia shadow, but a giant bulla was found at the same site. It was considered that it was necessary to treat this case with a combination of effective antibiotics and steroids in the early phase of the disease.


Monitoring for HIV-1, HIV-2, HTLV-I sero-progression and sero-conversion in a population at risk in east Africa.

Thirty-three individuals from East Africa, at risk for acquiring sexually transmitted infections, were selected to be monitored over a five month period for evidence of sero-progression and/or sero-conversion for human immunodeficiency virus type-1 and type-2 (HIV-1, HIV-2), and human T cell leukemia virus type-1 (HTLV-I). Initially, all sera were reactive by at least one retroviral screening assay, but most produced negative or indeterminate results by western blot assays. Five months after the initial screening, western blot assays indicated that one individual exhibited full sero-conversion for HIV-1; one HIV-1 positive individual also became positive for HIV-2; and two subjects showed sero-progression to become HTLV-I confirmed positive. Sera from fourteen individuals produced indeterminate results by western blot for HIV-1, ten of which were previously negative; the remaining four sera exhibited reactivity to at least one additional viral specific antigen after the five months. Circulating HIV-1 antigen was not demonstrated in any of the sera but DNA isolated from one of the individuals with indeterminate results produced a positive reaction for HIV-1 by the polymerase chain reaction.


Hepatitis B & D viral infections among schistosomal patients in Egypt.

A comparative study was done between schistosomal and non-schistosomal groups of acute and chronic HB patients to explore the possible role of schistosomiasis in predisposition to HBV and HDV infections in Egypt. The studied groups were 116 cases of acute hepatitis (78 cases without schistosomiasis and 38 cases with schistosomiasis). The second group of the study was 51 chronic HB patients (31 with schistosomiasis and 20 cases without schistosomiasis). All cases were tested for HBV markers and anti-HDV using ELISA technique. In acute hepatitis patients, the percentage of HBV infection as detected by HBsAg was significantly higher in the schistosomal group (63.15%: 24 out of 38) compared to non-schistosomal patients (37.17%: 29 out of 78) (Table 1). Also, Anti-HBs was detected in a significantly higher proportion among schistosomal group (85.71%: 12 out of 14) compared to non-schistosomal acute HB cases (44.9%: 22 out of 49) (Table 2). The infection rate of HBV (HBsAg+anti-HBs) was found to be statistically higher among schistosomal compared to non-schistosomal patients (94.73%: 36 out of 38 and 65.38%: 51 out of 78 respectively) (Table 3). As regards HDV among schistosomal and non-schistosomal patients suffering from acute HB, frequency of anti-HDV was found to be 33.33% (8 out of 24 HB cases) in schistosomal group versus 17.24% (5 out of 29 HB cases) in the non-schistosomal (Table 4). In chronic HB patients, anti HDV was present as 29.03% (9 out of 31) and 15% (3 out of 20) in schistosomal and non-schistosomal groups respectively (Table 5). But the differences between schistosomal and non-schistosomal groups, as regards delta infection (anti-HDV) among acute and chronic HB patients, were not statistically significant. From the present study, it was concluded that schistosomiasis contributes to significantly increased HBV infection and possibly also HDV infection.


Pathological changes in testes and liver of male albino rats after dermal exposure to DDVP insecticide.

Exposure of male albino rats to DDVP insecticide at sublethal dose of 30 mg/kg/day through dermal painting for a period of 90 days didn't show any intoxication symptoms or mortality. However, cytopathological changes in testicular and liver tissues were evident. There was a positive correlation between the degree of cellular damage and the period of insecticide administration. In general, damages were prominent in rats treated for 30 days or more. Histological examination of testes showed degenerative seminiferous tubules and fewer leydig cells. Hepatic cells were congested, atrophied and showed different stages of necrobiotic changes. This suggests a great care and caution for workers during different phases of DDVP insecticide handling.


An epidemiologic study of ovarian cancer. Part 11: Oral contraceptive use and menstrual events.

This work was conducted to investigate the potential risk factors which may contribute to the development of ovarian cancer. A retrospective analysis was adopted where 52 ovarian cancer cases and an equal number of a control group were obtained from the Western region of Saudi Arabia. This case-control study confirms that oral contraceptive use protects against the onset of ovarian cancer and that the decrease in the risk of the development of this disease is also directly related to the duration of use. Additionally, the study revealed a positive association between both age at menopause and hot flashes and the relative risk of ovarian cancer. On the contrary, age at menarche and premenstrual tension have been shown in this study to have no role as a risk factor in the development of ovarian cancer.


Cross sectional study of schistosomiasis among military recruits in Alexandria.

A cross-sectional survey for schistosomiasis infection was carried out among 1170 military recruits in Alexandria. Data on prevalence-intensity of infection-subjective symptoms and history of antischistosomal chemotherapy administration were collected from participants. The results confirmed the endemicity of S. mansoni and the low prevalence of S. haematobium infection in Delta region (33.1% and 1.1%) respectively. Previous antischistosomal chemotherapy administration was associated with decreased geometric mean egg count inspite the increase in prevalence. It is recommended that mass chemotherapy with praziquantel of this young active adult group would be of beneficial effect in decreasing schistosomiasis morbidity among an important large section of the community.


Association between chronic hepatitis B carrier state and schistosomiasis.

A case-control study was designed to investigate the association between chronic HB carrier state and schistosomiasis infection. Four hundred bilharzial and 370 non-bilharzial individuals were included in this study. Sera from all individuals were tested for HBsAg and antibodies to delta Ag using ELISA. Chronic HB carrier rate was significantly higher among bilharzial cases (12.5%) than non-bilharzial individuals (6.2%). However no association was observed between HBs antigenaemia and intensity of schistosoma infection estimated by geometric mean of number of S. mansoni eggs/gm stools and S. haematobium eggs/10 ml of urine. Among important hepatitis associated risk factors reported were parenteral injection, dental manipulation and hospitalization. Blood transfusion seemed to have very minor role. Antibodies to delta Ag were detected in 9.6% of chronic HBsAg carriers, especially in the high titered individuals.


Assessment of level of intellectual functioning among juvenile boy delinquents in Alexandria and its relation to behavioral deviance.

Sixty-five institutionalized boy delinquents in Alexandria aged 11 to 21 years were screened for intellectual functioning (I.Q. level) in relation to behavioral deviance. Findings revealed that the mean I.Q. score on the intelligence scale was within the average level of intelligence. The presence of behavior disorder varied insignificantly as a function of intellectual level. Results of this study do not indicate the prevalence of behavior disorders in relation to intellectual functioning in the total population of delinquent children not officially declared. However, the results could be a valid index of the demand for mental health services for the delinquent children, in whom "nonintellectual factors" (familial and psychosocial) might have a significant role in shaping their behavior.


Clinical and radiologic study of the frequency and presentation of chest infection in children with severe protein energy malnutrition.

The association between P.E.M. and frequent and severe life threatening infections including lower respiratory tract infections have been always reported. Lack of the usual general and local signs of infection in P.E.M. makes the diagnosis difficult and sometimes only postmortem. This study evaluated the frequency of chest infections as well as the sensitivity, specificity and predictivity of different signs and symptoms of the disease in 100 children with severe P.E.M. (marasmus, kwashiorkor, and marasmic kwashiorkor). Sixty two percent of the studied children had chest infection (33% pneumonia, 29% bronchitis). Although most patients were symptomatic, yet, signs and symptoms were few and mostly non specific. Chest roentgenograms are thus mandatory in evaluating patients with P.E.M. whenever possible. The only valuable signs suggestive of chest infection in P.E.M. were tachypnea (> or = 40/min) and/or chest indrawing. Both were moderately sensitive, highly specific and predictive of the disease particularly pneumonia. Their presence thus, its indicative of the need for early institution of antibiotic therapy even before the results of chest roentgenograms. Total Leucocytic count was of little diagnostic value while contrary to the common belief that tuberculin test is usually negative in P.E.M., the use of double the usual dose of P.P.D. (i.e. 10 TU) yielded positive reaction in some of the studied patients and thus must not be omitted from the routine investigations of malnourished patients.


Effect of dietary fat on serum and tissue lipids of adult rats.

The effect of 3 types of fat: 1) Ghee, 2) Corn oil, 3) Subsidized vegetable oil (SVO) on serum and tissue lipids was studied by using adult albino male rats mean weight 114 g. Rats fed diet containing SVO had the highest serum cholesterol and LDL-cholesterol concentrations than those fed diet containing ghee or corn oil. Serum high density lipoprotein-cholesterol (HDL) concentration was highest in animals fed the ghee and lowest with those fed the SVO diet. On the other hand phospholipids values tend to be lower when feeding diets containing oils. Also serum triglycerides levels were higher on saturated fat diet than on the unsaturated fat diets. The same trends were found for liver cholesterol as in serum cholesterol. SVO diet gave the highest liver cholesterol concentration. Also SVO gave the highest heart phospholipids values.


Tumor necrosis factor (TNF alpha) in lymphadenopathy and bone marrow involvement: histopathological and serological study.

Serum samples were collected from 40 patients with enlarged lymph nodes. Lymph node and bone marrow biopsies were performed and processed as usual. Tumor necrosis factor-alpha (TNF alpha) was determined in the sera by factor test human TNF alpha ELISA kit. Histopathological studies of lymph node and bone marrow biopsies were evaluated. The data obtained from this study showed that bone marrow was involved in only 5 patients and their TNF showed the lowest level in this study with a mean level 50 pg/ml. The highest level of TNF occurred in cases with granulomatous lymphadenitis (124 pg/ml) followed by reactive lymphadenitis (105 pg/ml). It can be considered that TNF reflects the immune status of the patient and its study in the serum can be of help in evaluating the progress of the disease. An extended study is need to evaluate the role of TNF-alpha as a prognostic marker in malignancy.


Evaluation of diagnosis of ovarian malignancy using immunohistochemical technique.

Immunohistochemical staining was performed on biopsy specimens from normal ovary and also from abnormal ovarian growth using monoclonal OKT9 antibody. The results showed positive reaction in 8.77% of normal ovarian specimens removed during laparotomy. The reaction was also positive in 15.7% in cases diagnosed by histological examination as benign ovarian growth. Specimens proved by histological examination to be malignant showed reaction with OKT9 in 100%. The significance of this finding is discussed.


A study of the morbidity pattern of referred patients and the effectiveness of the referral system in primary health care centers.

Patient referral system is considered to be an important element in achieving the objectives of the Primary Health Care services. Patients attending the Primary Health Care Center (PHCC) expect basic medical care and appropriate follow-up services. Thus, patients requiring further evaluation and treatment are referred to a secondary health care facility. In this study the morbidity pattern as well as the referral system was evaluated in selected PHCC in the city of Jeddah. A systematic random sample of all the patient referrals from selected PHCC's were analyzed. A total of 1,164 referrals were studied, 59.9 per cent were females and 40.1 per cent were males. The contents of referral letters from PHCC to hospitals as well as feed back from hospitals were analyzed. The majority of referrals were for the age group 25-44 years old 458 (39.3%). The results demonstrated that 5 per cent of patients were routinely referred to the secondary health care centers, and the feedback from these secondary health care facilities was (22.7%). It was also noted that the majority of referral letters lack commonly accepted standards of information about the patient. It was concluded that the follow-up and feed-back system needs to be reinforced. The primary health care providers need to review the patient referral system and implement specific criteria for the optimum utilization of this essential service for the benefit of the community.


Study of the effect of birth spacing on maternal health.

This study aims at identifying the effect of birth spacing on maternal health. The study was carried out on a representative sample of 324 married women at the fertile age period and having at least two children. The result of this study revealed that women practicing birth spacing were 33.3% of the studied sample. The mean age was 34.4 +/- 5.3 years and 31.3 +/- 5.7 years for improper and proper birth spacing respectively. Improper birth spacing women constituted 70.2% of low social class. Out of the total number of improper birth spaced women, 41.7% were overweight, 25.9% were hypertensive, 57.4% had varicose veins, and 18.1% had low limb oedema. Concerning Gynecological findings; vaginal discharge and cervical erosion were 70.4% and 19.4% of improper birth spacing women respectively, laboratory investigations revealed that anaemia and glucosuria were 88.4% and 12.5% of improper birth spacing women respectively. Good knowledge and favorable attitude were 88% and 100% of properly birth spaced women. The mean number of gravidity, number of abortions and number of infant deaths were 6.6 +/- 2.8; 0.9 +/- 1.3 and 1.36 +/- 1.63 of improperly birth spaced women respectively and 4.2 +/- 1.7; 0.6 +/- 1.1 and 0.41 +/- 0.81 of properly birth spaced women respectively. It could be concluded that young women were practicing birth spacing more properly. Rural origin women are less practicing birth spacing. Medical and Gynecological disorders were more among improper birth spacing women. Pregnancy wastage are more among improper birth spacing. It is to be recommended that more efforts should be done among low social class. Encouraging young women to practice pre-natal care. Emphasizing on the practice of proper birth spacing and small family size.


Phospholipase A2 inhibitors from marine organisms.

This review of phospholipase A2 (PLA2) inhibitors from marine organisms presents a compilation of research in this field over the past decade. As an introduction to the research on marine natural products, there is an overview of the role of PLA2 in inflammation that provides a rationale for seeking inhibitors of PLA2 as anti-inflammatory agents. A radiometric assay to measure inhibition of bee venom PLA2 is described in detail. Examples of marine natural products that inhibit PLA2 are manoalide and its derivatives, scalaradial and related compounds, the pseudopterosins, the vidalols, and a group of terpenoids that contain masked 1,4-dicarbonyl moieties.


Strategies and tactics for the synthesis of oxygenated natural products.

The total synthesis of the ansa antibiotic macbecin I [1] is described exploiting an approach that features the oxidative transformation of furans into hydropyrans that then serve as conformationally biased templates for stereoselective refunctionalization and elaboration. A novel variant of the Mitsunobu reaction was developed that may be applied to the inversion of hindered secondary alcohols. In work directed toward the total synthesis of the antifungal antibiotic ambruticin [3], new and general methods have been invented for the asymmetric synthesis of functionalized cyclopropanes by intramolecular cyclopropanations of omega-unsaturated diazoacetates and the convergent stereoselective synthesis of trisubstituted alkenes.


Scoparic acid A, a beta-glucuronidase inhibitor from Scoparia dulcis.

The 70% EtOH extract of Scoparia dulcis showed inhibitory activity against beta-glucuronidase from bovine liver. Bioassay-directed fractionation of the active extract led to the isolation of three labdane-type diterpene acids, scoparic acid A [1] [6-benzoyl-12-hydroxy-labda-8(17), 13-dien-18-oic acid], scoparic acid B [2] [6-benzoyl-14,15-dinor-13-oxo-8(17)-labden-18-oic acid], and scoparic acid C [3] [6-benzoyl-15-nor-14-oxo-8(17)-labden-18-oic acid], the structures of which were established by spectral means, including X-ray analysis. Scoparic acid A was found to be a potent beta-glucuronidase inhibitor.


Cytotoxic activity of tetraprenylphenols related to suillin, an antitumor principle from Suillus granulatus.

Cytotoxic activity against three tumor cell lines (KB, P-388, and NSCLC-N6) has been determined for 14 natural and semisynthetic tetraprenylphenols. Structure-activity relationships have been examined.


Anti-tumor-promoting activities of afromosin and soyasaponin I isolated from Wistaria brachybotrys.

Afromosin [1] and soyasaponin I [2] isolated from Wistaria brachybotrys exhibited remarkable inhibitory effects on mouse skin tumor promotion, and afromosin also exhibited a significant inhibitory effect on pulmonary tumor promotion. The combined effects of these compounds on the two-stage skin carcinogenesis were also examined, and it was concluded that the combination of 1 with 2 enhanced the inhibitory effect.


Identification of the new 10,15-eicosadienoic acid and related acids in the opisthobranch Haminaea templadoi.

The free fatty acids of the Mediterranean opisthobranch Haminaea templadoi were isolated and characterized, revealing the presence of the new 10,15-eicosadienoic acid [1] and several unusual cis delta 6 monoenoic acids, such as (Z)-6-tetradecenoic acid, (Z)-6-pentadecenoic acid, and (Z)-6-heptadecenoic acid. These results reveal some previously unrecognized fatty acids in mollusks.


Antimalarial activity of sesquiterpenes from the marine sponge Acanthella klethra.

Five sesquiterpenoids containing isonitrile or isothiocyanate groups were isolated from the sponge Acanthella klethra. Compounds 1 and 2 were identified as axisonitrile 3 and the corresponding isothiocyanate derivative, respectively. Compounds 3-5 were found to be eudesmane sesquiterpenes. None of these compounds was cytotoxic toward cultured KB-3 cells, but varying degrees of activity were observed with cultured Plasmodium falciparum. Compound 1 demonstrated greatest promise as an antimalarial agent.


Distribution of circulating beta-carotene in human plasma lipoproteins.

We examined the distribution of beta-carotene in plasma lipoprotein fractions. In healthy children and adults, LDL contained more beta-carotene than did HDL, but in cord blood more beta-carotene was found in HDL than in LDL. After the oral administration of beta-carotene, its plasma level rose although its distribution in the individual lipoprotein fractions did not change. Among disease conditions associated with hyperlipidemia, the ratio of beta-carotene to plasma lipids was highest in anorexia nervosa, while nephrotic syndrome and diabetes mellitus had similar ratios to each other.


High-performance liquid chromatographic separation and spectral identification of the photoreaction products of methyl 5,8-epoxyretinoate.

Photoreaction of methyl 5,8-epoxyretinoate was investigated. Irradiation of methyl 5,8-epoxyretinoate in acetonitrile with a light from a high-pressure mercury lamp or a daylight fluorescent lamp afforded three new products, which were purified by high-performance liquid chromatography. They were characterized on the basis of spectroscopic data as 11-(Z), 13-(Z), and 11,13-di(Z) isomers, respectively.


Determination of absorption and endogenous excretion of iron in man by monitoring fecal excretion of a stable iron isotope (58Fe).

The absorption and endogenous excretion of iron in man was studied by monitoring the fecal excretion of a stable iron isotope (58Fe). The study was carried out for 12 healthy volunteers who were divided into two groups. Group I received 58Fe-labeled ferric ammonium citrate (III) (58FeAC) equivalent to 6 mg of iron as a control, and group II received a combination of 500 mg of vitamin C and 58FeAC. A new formula was used to calculate the 58Fe absorption ratio reflecting the pool of iron in the intestinal cells, and the ratio was compared with that obtained from Janghorbani's formula, which has been used as one of the common methods. As a result, the 58Fe absorption ratio in group II was statistically significantly higher than that of group I (34.4 +/- 6.1% vs. 15.0 +/- 5.5%, M +/- SD) using Janghorbani's formula. The similar absorption ratio (34.1 +/- 6.0% vs. 14.8 +/- 5.5%) was also obtained by our new formula. Our results confirmed the previous findings that the availability of iron is stimulated by the supplementation of vitamin C. Both formulae agreed in the absorption of iron, indicating that the endogenous excretion of iron (caused by the desquamated cells) in the intestine does not disguise the iron absorption.


Impact of lead toxicity on brain metabolisms of nucleic acid and catecholamine in protein malnourished rats.

The brain biochemistry in terms of certain key substances of brain were studied in 18% protein and 6% protein-fed rats following lead ingestion at a level of 1% in the diet. Lead ingestion diminished the protein and increased the RNA content of brain, and, consequently reduced the protein/RNA ratio. The RNA/DNA ratio in brain was elevated in lead toxicity, while the protein/DNA ratio remained unaltered. The RNase and DNase activities of brain were decreased. Lead treatment diminished the glutathione (GSH) level of blood but the GSH level of brain was not altered significantly by the lead treatment. The plasma protein level was also diminished after lead treatment. The effects of lead on some of these parameters were found to be more pronounced in rats receiving the 6% protein diet. The serotonin (5-HT) level of brain was reduced, while the norepinephrine (NE) and dopamine (DA) levels of brain were elevated following lead treatment. The monoamine oxidase (MAO) and tryptophan hydroxylase (TPH) activities and 5-hydroxy-indole acetic acid (5-HIAA) content of brain were elevated in lead-ingested rats. The effects of lead on these parameters were found to be potentiated when the rats were fed on a 6% protein diet. These studies suggest that lead at the present dose affects brain biochemistry in terms of both nucleic acids and amine metabolism, and protein deficiency potentiates some of these lead-induced changes.


Lipophilic soluble protein represents labile protein in rat liver.

Lipophilic proteins, having higher turnover rates than the average of the total soluble protein pool, were separated from soluble rat-liver proteins on alkyl agarose column. The quantitative immunoprecipitation, using the antibody against the lipophilic proteins, showed that the soluble proteins from the liver of fed rats contained about twice as much lipophilic proteins as that of 3-day-starved rats. This result indicates that the lipophilic proteins, at least in part, represent labile protein in rat liver.


The effect of dietary safflower phospholipid and soybean phospholipid on plasma and liver lipids in rats fed a hypercholesterolemic diet.

The effect of dietary safflower phospholipid (Saf-PL) and soybean phospholipid (Soy-PL) on plasma, liver, and fecal lipids in rats fed a hypercholesterolemic diet was compared with that of triglyceride mixture (controls). Triglyceride mixture (SP-Oil) of safflower oil and palm oil (8:2) contained almost comparable amounts of linoleic acid to safflower phospholipid or soybean phospholipid. Concentration of total cholesterol in plasma of rats fed the Saf-PL and Soy-PL diets were significantly decreased in comparison with that of the SP-Oil diet. Similarly, both Saf-PL and Soy-PL induced a reduction in the concentration of liver cholesterol compared with SP-Oil; Saf-PL indicated the lowest value. Saf-PL only significantly increased the level of high density lipoprotein (HDL) cholesterol. The level of chylomicron plus very low density lipoprotein (VLDL) cholesterol was lower in rats fed the Saf-PL and Soy-PL diets than that of the SP-Oil diet. The activity of plasma lecithin-cholesterol acyltransferase (LCAT) was increased in rats fed Saf-PL and Soy-PL. Saf-PL and Soy-PL caused an enhanced excretion of fecal neutral steroids, but not acidic steroids compared with SP-Oil. These results suggest that, in addition to soybean phospholipid, safflower phospholipid suppresses the elevation of plasma and liver cholesterol and that this effect may be brought about by inhibiting the absorption of cholesterol in the small intestine.


Hemoglobin repletion in anemic rats fed a new bean cultivar (Phaseolus vulgaris L.) as source of iron.

Utilization of iron from a new cultivar of dry bean (Carioca 80 SH) was estimated using anemic rat by two methods: the slope ratio and the hemoglobin regeneration methods. The bean was incorporated into the diet in the form of whole bean flour (WBF) 7.45 mg Fe/100 g or as partially decorticated bean flour (DBF), 8.57 mg Fe/100 g. Hemoglobin concentration in the rats' blood at the beginning of the experiment averaged 13.79 +/- 0.33 g Hb/dl; at the end of the depletion period it ranged from 5.62 +/- 0.38 to 6.30 +/- 0.39 g Hb/dl blood, difference which was not statistically significant (p < or = 0.05). The bean iron relative biological value (RBV, relative to FeSO4 = 100) evaluated by the slope ratio method, was 74% for the WBF and 77% for the DBF. The hemoglobin regeneration efficiency was 60.4 +/- 6.5, 50.8 +/- 3.2, and 52.7 +/- 5.7%, respectively, for the iron sulfate (reference source), the WBF, and the DBF.


Obligatory nitrogen losses in pregnant rats with special reference to estimation of net protein utilization.

For estimation of net protein utilization of dietary proteins during pregnancy, obligatory nitrogen losses were measured in protein-deficient rats in which pregnancy was maintained by administration of ovarian steroids. On shift from normal to protein-free diet, urinary nitrogen, expressed as mg/day or mg/100 g BW per day, decreased initially rapidly and then gradually during the first two weeks in both pregnant and nonpregnant rats. However, urinary endogenous nitrogen increased during the final week of pregnancy, whereas it continued to decrease in nonpregnant controls. The endogenous urinary nitrogen excretions during early-mid and late pregnancies were significantly higher in pregnant rats (666 mg/15 days and 234 mg/6 days, respectively) than in nonpregnant animals (585 mg/15 days and 153 mg/6 days, respectively), indicating pregnancy-induced protein hypercatabolism. The metabolic fecal nitrogen excretions in pregnant and nonpregnant rats were comparable. In pregnant rats, a protein-free diet resulted in decrease of basal energy expenditure, from 24 kcal/day on day 1 to about 15 kcal/day on days 16, 19 and 22 of pregnancy. Thus, the ratio of endogenous urinary nitrogen to basal energy expenditure increased in late pregnancy, indicating that "the law of a constant relationship of minimal nitrogen and energy output" is not applicable to the pregnant animals. We discuss which values for obligatory nitrogen loss should be used for estimating the net utilization efficiency of dietary proteins in pregnancy.


Net utilization of various levels of whole egg protein in pregnant rats.

Net protein utilization (NPU) was examined in pregnant rats fed various levels (1, 3, 6, 10 and 20%) of whole egg protein (WEP), based on their obligatory nitrogen losses. On increase in dietary protein, nitrogen balance improved curvilinearly and the NPU decreased exponentially in both pregnant and nonpregnant rats. The utilization efficiency was high in rats fed marginally low protein diets, mainly due to lower urinary nitrogen levels than the obligatory levels of nitrogen loss. The NPUs in pregnant rats fed 1, 3, 6, 10 and 20% WEP diets were 103, 99, 78, 66 and 46, respectively. These values were 15 to 20% higher than those in nonpregnant rats because in pregnant rats obligatory urinary nitrogen loss was higher and the animals took more energy. The problems in application of the NPUs in pregnant rats for estimating the protein allowance of pregnant humans are discussed.


Umbilical ascorbic acid levels in fetal distress.

Umbilical arterial and venous blood samples were obtained at birth immediately after clamping the cord in 38 infants. Simultaneously, maternal arterial samples were collected. Arterial blood samples were analyzed for acid-base blood gas content and venous blood samples were analyzed for plasma ascorbic acid levels. The umbilical plasma ascorbic acid level was significantly higher when compared with maternal plasma levels (172.9 +/- 39.2 vs. 57.8 +/- 21.0 mumol/liter, p < 0.0001). Correlations between maternal ascorbic acid levels and umbilical cord levels proved to be insignificant. Umbilical ascorbic acid levels in the 2 groups of infants characterized by the presence or absence of fetal distress showed significantly higher levels in the fetal distressed group (17 infants) when compared to the non-distressed group (21 infants)--191.9 +/- 36.0 vs. 157.4 +/- 34.6 mumol/liter, p < 0.005. The use of an umbilical cord ascorbic acid cut-off point of 95.8 mumol/liter gave a sensitivity of 76% and a specificity of 67% as predictors for the presence or absence of fetal distress (p < 0.025). The results of the present study demonstrate a substantial increase in ascorbic acid levels in infants exposed to intrapartum fetal distress, without any clinical sign of such insult at or after birth.


A simple enzymatic quantitative analysis of triglycerides in tissues.

We determined a method to measure the triglyceride levels in tissues by using a modified enzymatic kit. This enzymatic kit was originally designed to be used to measure the triglyceride levels in plasma. Our method of triglyceride level determination includes dissolving the tissue lipid extracts in an alcohol. Before using the enzymatic kit directly, the lipids were dissolved in tert-butyl alcohol, then a Triton X-100/methyl alcohol mixture was added (1/1 by volume). The presence of organic surfactants such as tert-butyl alcohol and methyl alcohol, and of a surfactant such as Triton X-100, did not interfere with the enzymatic activity. This method enabled us to determine triglyceride levels between 10 and 90 nmol, by using a spectrophotometer to measure the absorbances.


The morphological and biochemical changes in skeletal muscle fibers by dietary protein restriction.

The effects of dietary protein restriction on skeletal muscle fibers were studied according to morphological and biochemical approaches. Protein and DNA content of quadriceps muscles from young adult rats were decreased by the low protein and protein-free diet. Morphological examination demonstrated that there was a significant decrease in the size of muscle fibers without change in their numbers due to protein restriction. The protein/DNA ratio, accepted as an index of cell size in biochemical approaches, was compared with cell size on photomicrographs. Actual fiber size appeared much smaller than that indicated by the protein/DNA ratio.


Thiamin triphosphate does not affect contraction of skinned fibers.

Effects of thiamin triphosphate (TTP) on contraction of chemically skinned fibers prepared from the extensor digitorum longus muscle of guinea pigs were investigated. The addition of TTP at 40 microM concentration affected neither Ca2+ uptake nor Ca(2+)-induced Ca2+ release by sarcoplasmic reticulum. Contraction of myofibril was not affected by TTP either.


[Structural studies of malaria vaccine].

Malaria still remains a serious health problem in large areas of the world, and in this article, recent research progress mainly made by us toward malaria vaccine development has been reviewed. 1) Peptide vaccines (antigens) of immunodominant tetrapeptide repeats (NANP and NVDP) of the circumsporozoite surface protein of the malaria parasite, Plasmodium falciparum, were genetically produced in E. coli as a fusion protein with a part of human growth hormone, which has affected on the conformations and immunogenicities of the peptide vaccines. 2) Monoclonal antibodies against the peptide antigens were produced by fusion of mouse spleen cells with myeloma cells, and the F (ab's) obtained by partial digestion of the antibodies with papain were used for the measurement of the dissociation constants of the antigen-antibody complexes. The amino acid sequence of the Hv region in F(ab) domain was also deduced from its nucleotide sequence.


[Studies on the mechanism of drug distribution in tissues].

The importance to elucidate the mechanisms of drug distribution in tissues has been discussed in this review. By considering several factors such as tissue binding, plasma binding, membrane permeability and tissue interstitial fluid space, the tissue distribution states of drug have been characterized based on the biochemical and pharmacokinetic studies. These physiological pharmacokinetic analyses have been applied to evaluate the determinant factors of inter-organ, drug to drug, interspecies or age related changes of tissue distribution of drug. The mechanisms of membrane permeability of drug which could play the most important role to regulate the drug distribution have been discussed. The drug distribution to the brain is strictly restricted by the function of the blood-brain barrier (BBB). The drug transport mechanisms at the BBB have been discussed. Especially, the role of carrier-mediated and absorptive-mediated transport systems at the BBB has been focused on.


[Quenching of ethidium-DNA fluorescence by novel acridines with antitumor activities].

In order to elucidate the relationships between the antitumor activity and the molecular structure of novel acridine derivatives (1a-f, and 2a-e in Chart 1) the DNA-binding properties (intercalation) of the derivatives were examined by the quenching in fluorescence of an ethidium-DNA complex, which may be caused by the displacement of DNA-bound ethidium by a second DNA-binding ligand, acridines. The concentration (C50 value) of the acridine necessary to reduce the initial fluorescence of DNA-bound ethidium by 50% showed a good correlation with their antitumor activities. The fluorescence quenching of the acridines was examined using 4'-(9-acridinylamino)- methanesulfonanilide (amsacrine, AMSA) as a typical standard of the second DNA-bound ligand, and calf thymus DNA with an apparent site size of two base pairs.


[Activity of Enterococcus faecalis (FK-23) preparation as a biological response modifier].

The biological activity of a preparation of heat killed cells of Enterococcus faecalis, FK-23 which was isolated from the feces of a healthy human, was investigated in C3H/He mice. Intraperitoneal injection of the preparation caused an accumulation of neutrophils and macrophages in the peritoneal cavity of the mice 6 h later. As a parameter of the activation of macrophages, the effect of the FK-23 preparation on the production of tumor necrosis factor (TNF) was examined. The mice were given two consecutive intravenous injections of the preparation at a dose of 10 micrograms/mouse and, 3 h later, of 300 micrograms/mouse. The TNF level in the sera reached 99 U/ml in mice 2 h after the second injection. This preparation also stimulated peritoneal macrophages to produce TNF in vitro and increased the capacity of neutrophils to adhere to plastic plates and to release active oxygens, but did not induce blastogenic transformation of lymphocytes. These results suggest that the FK-23 preparation is a biological response modifier (BRM) with various activities on phagocytes similar to a streptococcal antitumor agent, OK432.


[Effects of ascorbic acid on the metabolic fate and the free radical formation of iproniazid].

The effects of ascorbic acid (AA) on the metabolic fate of iproniazid (IPN) and on the free radical intermediates derived from IPN were investigated in rats. After oral administration of IPN with or without AA, the plasma concentration and the urinary excretion of IPN and its metabolites were determined by gas chromatography-mass spectrometry using stable isotope labeled compounds as internal standards. In the excretion of IPN and its metabolites except hydrazine (Hy), the differences between co-administration and single administration were not observed. The excretion of Hy, which is a known hepatotoxic metabolite, decreased clearly in the co-administration of IPN and AA. When IPN and AA were co-administered orally, the profiles of plasma levels of IPN and its metabolites were almost similar after the administration of IPN alone. Furthermore, no differences between i.v. co-administration and i.v. administration alone were observed. These results indicated that AA did not affect both absorption and metabolism of IPN. By the electron spin resonance (ESR) spectroscopy and spin-trapping technique, the ESR signals due to the alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN) adducts induced by isopropylhydrazine (IP-Hy) were two-fold higher than those by IPN in microsomal systems. The free radical formations of IPN and IP-Hy were significantly inhibited by AA in a dose dependent manner. The 4-POBN-trapped radical species generated from IPN and IP-Hy were presumed to be an isopropyl radical by the results of mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)


[Antimutagenic substances in the Armeniacae semen and Persicae semen].

Using the Ames/Salmonella/microsome assay, we examined the antimutagenic effect of the hexane extract of Armeniacae semen (apricot (Prunus armeniaca L.) seed), Persicae semen (peach (P. persica Bat.) seed), and seeds of cherry (P. avium L.), plum (P. salicina Lindle) and almond (P. dulcis Mill). Hexane extracts of Armeniacae semen and Persicae semen inhibited the mutagenicity of benzo[a]pyrene (B[a]P), but those of seeds of cherry, plum and almond did not. The mutagenicities of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) were also inhibited by the extracts of Armeniacae semen and Persicae semen. Inhibitory substances in Persicae semen were fractionated by silica gel column chromatography and high performance liquid chromatography, and were identified as oleic acid and linoleic acid. The contents of oleic acid and linoleic acid were 0.7 and 0.4% in the hexane extract of Armeniacae semen, and 1.5 and 0.5% in that of Persicae semen, respectively.


[Determination of scopolia extract in commercial gastrointestinal drugs by high-performance liquid chromatography].

Tropane alkaloids, contained in gastrointestinal drugs including Scopolia Extract, were determined using high-performance liquid chromatographic method. Tropane alkaloids in commercial drugs were extracted with 0.5 N hydrochloric acid test solution. This solution was adjusted to pH 10.0 with a strong ammonia solution, extracted with ethyl ether, and separated on TSKgel ODS-120T (4.6 mm i.d. x 15 cm; temperature, 30 degrees C; flow rate, 1.5 ml/min; detector, UV 210 nm) with a mixture of 1/15 M sodium phosphate buffer (pH 2.5) and acetonitrile (68:32) containing 12 mM sodium dodecyl sulfate. The contents of atropine in the gastrointestinal drugs were 0.25-0.34 mg (coefficient of variation = 0.20-2.61%) a day.


[Contrast media in hepatic MRI].

This article is a review of the current commercial MR contrast media (gadolinium chelates) and of the products that are not yet on the market and are under trial in man (super-magnetic iron oxides, manganese compounds) or only in animals (ferric chelate, liposomes containing gadolinium compounds, gadolinium chelate/human serum albumin compounds, hepatic asialoglycoprotein receptors).


[Imaging of HIV+ abdominal involvements].

Abdominal symptoms are among the most frequent complaints of patients with AIDS. Because precise diagnosis from symptoms alone is difficult, the contribution of radiologist is important to fill in evaluating the cause of various illnesses. The review describes common clinical symptoms and lists the most likely causes with discussing the most appropriate imaging evaluation. For diagnosis and treatment, the most frequent and characteristics radiographic findings are described.


[Interstitial pulmonary involvements in polymyositis and dermatopolymyositis. Apropos of 3 cases. Review of the literature].

The authors report 3 cases of myositis associated with pulmonary lesions that preceded or succeeded the muscular disorder. In one of these cases, which was particularly difficult to diagnose, the patient's serum was positive for the anti-Jol antibody. These 3 cases have encouraged the authors to review the literature with particular attention to the diagnostic approach, the latest physiopathological data and the therapeutic basis of the "specific" pulmonary lesions associated with polymyositis and dermatomyositis.


[Anguilluliasis of the small intestine and AIDS. A case and review of the literature].

The authors report about one patient with an Acquired Immune Deficiency Syndrome (AIDS) presenting with strongyloidiasis involving the small bowel. On the basis of this observation, they describe the appearances of small bowel involvement by strongyloidiasis in patients with AIDS. They emphasize the main features differentiating these cases from the usual affection, namely the severity and diffusion of the lesions, as well as the presence of a very extensive associated lymphoid nodular hyperplasia.


[Breast microcalcifications].

Microcalcifications of the breast are better recognized as the quality of mammographs is improving. The clinical examination and complementary modalities are often essential to evaluate their significance and point out to an indication for surgery. However, especially when the microcalcifications are detected during a systematic examination, a strict analysis of mammographs is essential. The number of useless punctures must be reduced, as their psychological impact and socioeconomic weight are already demonstrated. Although there is no consensus, most recent publications contain ideas converging on the selection of the indications for a histological control on the basis of an accurate semiological study.


[Ultrasonographic aspects of hemolytic uremic syndrome in children. Apropos of a series of 21 cases].

The sonographic expression of the hemolytic-uremic syndrome in children is a cortical hyper-echogenicity, which has a real prognostic value in comparison to the clinical criteria. In addition, renal ultrasonography with Doppler is useful to predict the evolution of the condition, and may help the clinician to define the therapeutic choices.


[Merkel cell tumor. Contribution of imaging apropos of a case].

This rare malignant skin tumor, of controversial origin, possesses marked potential for dissemination. A case is reported in which medical imaging technics allowed close surveillance of the course of the disease.


[Chordoma of the base of skull. Apropos of 3 cases].

The authors report 3 cases of skull base chordomas. In 2 cases, skull radiographies and computed tomography found lytic lesions of sphenoid and clivus, with calcifications into the tumors. In the third case, radiological findings suggest a naso pharynx tumor.


Localization of the enzyme neutral endopeptidase to the human synovium.

Neuropeptides, contained within sensory nerve fibers in the synovium, are present in inflammatory joint fluids. The potency of these peptides in vitro has led to the hypothesis that enzyme degradation systems are operative in vivo. To address this question we localized neutral endopeptidase (NEP; EC 3.4.24.11) in human synovium. The normal human synovium failed to show any immunoreactivity for NEP. In the disease groups there was intense staining of cells surrounding blood vessels. Our data are consistent with the hypothesis that a proportion of synovial fibroblasts are the major source of this enzyme in the arthritic joint.


Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: I. Nonsteroidal antiinflammatory drugs.

The probability of continuation of a particular nonsteroidal antiinflammatory drug (NSAID) over 5 years was estimated for 1,775 courses taken by 532 patients with rheumatoid arthritis treated in 7 rheumatology private practices. Similar results were seen for 15 different NSAID--48% of courses were continued at 12 months, 36% at 24 months, and 20% at 60 months. Only acetylated salicylates, other than plain aspirin, were continued significantly longer than any of the other NSAID. The probability of continuation of plain aspirin was similar to other NSAID, including nonacetylated salicylates and nonsalicylate NSAID. The first NSAID taken by an individual patient was continued only marginally longer than the 4th NSAID taken by the same patient. While most NSAID courses were not continued for long periods, 20% were continued for longer than 5 years, suggesting effective longterm results in this minority of courses.


Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone.

The probability of continuation of 1,077 courses of 2nd line drugs taken by 532 patients with rheumatoid arthritis treated in 7 rheumatology private practices was examined. This probability was that 50% of courses were continued over 10 months for oral gold, 20 months for hydroxychloroquine, 21 months for penicillamine, 25 months for parenteral gold, 27 months for azathioprine, and more than 60 months for methotrexate (MTX). MTX and prednisone were the only drugs continued by more than 50% of patients after 60 months, while about 20% of courses of other 2nd line drugs other than oral gold were estimated to be continued at 60 months. Estimated drug continuation did not differ significantly according to age, duration of disease, or whether the drug was the first, second, or 3rd 2nd line drug used. Some patients took each 2nd line drug for more than 5 years, suggesting a favorable experience, but most courses were not continued beyond 2 years.


Sex hormones and bone metabolism in postmenopausal rheumatoid arthritis treated with two different glucocorticoids.

To investigate the effect of low doses of 2 different glucocorticoids on bone mass, sex hormone status and bone metabolic indices, a study was undertaken in 16 postmenopausal women with rheumatoid arthritis (RA) receiving < 15 mg/day of deflazacort and in 16 patients with RA matched for age, years postmenopause and disease duration, receiving < 10 mg/day of prednisone. Sixteen healthy postmenopausal women and 16 nonsteroid treated patients with RA were also studied as control groups. Vertebral bone density (vBMD) was lower (mean +/- SD: 0.65 +/- 0.07 vs 0.73 +/- 0.09 g/cm2; p < 0.02) in prednisone treated patients than in deflazacort treated patients, whose vBMD values were similar to those of nonsteroid treated RA. No significant difference was found as for radial bone mineral content. Circulating levels of estradiol, dehydroepiandrosterone sulfate, androstenedione and progesterone were low in all patient groups with RA when compared with healthy controls. The prednisone treated patients showed significantly lower values of all sex hormones with respect to deflazacort treated patients. Osteocalcin values were also lower (3.0 +/- 1.4 vs 3.9 +/- 1.6 ng/ml; p < 0.05) in prednisone treated patients with respect to deflazacort treated group. Glucocorticoid treated patients showed a direct correlation (r2 = 0.39) between vBMD and plasma estradiol levels, while no correlation was found with osteocalcin values. In conclusion, our postmenopausal patients with RA treated with low dose prednisone had reduced levels of sex hormones and osteocalcin and reduced vertebral bone mass. Comparable doses of deflazacort showed only a mild inhibitory effect on sex hormones and osteocalcin, and did not show any detectable effect on bone mass.


Relationship of changes in helplessness and depression to disease activity in rheumatoid arthritis.

We investigated the relationship between changes in helplessness and depression to disease activity in rheumatoid arthritis (RA). Sixty-three men with RA were examined at baseline, 3 months, and 6 months. Joint counts, immunophenotypic analyses of peripheral blood lymphocytes, and measures of psychological status were obtained at each examination. Zero-order correlations between psychological change and disease activity change from baseline to 6 months were not significant, but hierarchical multiple regression analyses revealed that changes in affective state were significantly related to joint counts at 6 months. Additionally, changes in absolute numbers of HLA-DR+ (human leukocyte antigen DR type) cells were significantly related to joint counts at 6 months. When absolute numbers of HLA-DR+ cells were entered prior to affective state in a hierarchical multiple regression, affective state was only marginally statistically significant. The study shows that longitudinal relationships between affective changes and disease activity are moderated by intervening variables such as immunologic activation.


Severity of disability and duration of disease in rheumatoid arthritis.

A longitudinal sample of patients with rheumatoid arthritis (RA) from Santa Clara County, CA was analyzed. Severity was measured with the Disability Index from the Health Assessment Questionnaire (HAQ). First, 6 cohorts were created of women and men with 0 to 10, > 10 to 20, and > 20 years of duration of illness in 1981. Experiences of the 6 cohorts were studied from 1981 to 1989. For both sexes, and both samples which alternately included and excluded the deceased, persons with > 20 years of duration experienced faster deterioration than those with < 20 years. Second, multiple regression models were estimated which treated the Disability Index as the dependent variable. In the regression models, the Disability Index worsened more quickly for women than men, for persons with few rather than many years of education, and for older than younger persons. Regression models which excluded an intercept term suggested a unique "S" shaped curve that described the Disability Index and duration relation.


The sense of coherence questionnaire in patients with rheumatic disorders.

Aaron Antonovsky's Sense of Coherence (SOC) questionnaire with its 3 subscales is designed to measure strengths within individuals that allow them to survive in the face of extreme stresses, including chronic illness. We administered the SOC to 1333 patients with rheumatic disorders. Although the instrument had high alpha reliability, factor analysis did not support the concept of distinct subscales. The SOC was strongly related to the Arthritis Impact Measurement Scales anxiety and depression scores (r = -0.63 to -0.69), less strongly related to clinical variables (r = -0.20 to -0.33), and was minimally related to demographic variables. When psychological variables were controlled for, almost no association between the SOC and clinical variables remained (r = 0.06). Whether the SOC will be more useful than standard psychological instruments awaits the result of ongoing studies.


Autoantibodies versus clinical symptoms in blood donors.

A group of 255 blood donors was analyzed for the presence of serum autoantibodies, e.g., antinuclear antibodies, smooth muscle antibodies, antimitochondrial antibodies, antiparietal cell antibodies and antireticulin antibodies by indirect immunofluorescence microscopy. The 37 (15%) who had autoantibodies underwent examination and extended laboratory investigation. We found no strong evidence of disease in any of the blood donors with autoantibodies.


Absence of HLA-B8 and HLA-DR3 in Japanese patients with Sjögren's syndrome positive for anti-SSA(Ro).

Forty Japanese anti-SSA(Ro) positive patients with Sjögren's syndrome were typed for HLA-A, B, C, DR and DQ antigens. No patient had either HLA-B8 or HLA-DR3 which has been reportedly associated with the immune response to SSA(Ro) antigens in white and black patients. Our patients had higher frequencies of HLA-DRw8 and HLA-DRw52 than the control population.


Fibroblast growth factors released by wounded endothelial cells stimulate proliferation of synovial cells.

We demonstrated that vascular endothelial cells mechanically wounded by scraping from the substratum were able to release growth promoting factors for synovial cells as well as for endothelial cells. The wounded endothelial cell conditioned medium stimulated the proliferation of synovial cells derived from different human donors dose dependently and induced transit of growth arrested synovial cells (predominant in the G0 and G1 phases), through the S phase and into the G2 and M phases. When the wounded endothelial cell conditioned medium was applied to heparin-sepharose columns, mitogenic activity was eluted with 2.0 M NaCl. The mitogenic activity in wounded endothelial cell conditioned medium, which was heat sensitive, was inhibited by protamine sulfate and a specific mouse monoclonal antibody against basic fibroblast growth factor (bFGF). Our results are evidence that the wounded endothelial cell conditioned medium contained growth promoting factors for synovial cells, including bFGF. We also showed the presence of bFGF in the endothelial cells of the small blood vessels and stromal synovial fibroblast-like cells in patients with rheumatoid arthritis (RA). Our results suggest that the endothelial cells in the luxuriant capillaries in the synovial tissues from patients with RA may have a critical role in the stimulation of neighboring synovial cell proliferation, resulting in pronounced synovial hyperplasia.


Predictors of functional outcomes after arthroscopic partial meniscectomy.

To confirm previous studies that have identified knee osteoarthritis as the principal correlate of poor outcomes after arthroscopic partial meniscectomy (APM), we considered a range of other preoperative characteristics using multivariable analyses to control for confounding variables. One hundred five patients who had APM were studied. Selected demographic and clinical features were obtained from charts and operative notes. Preoperative and current functional status were determined by patient interviews. The principal outcomes were functional status at the time of followup, measured by the Physical Activity Scale of the SF-36 Health Status Inventory, and the Lysholm Knee Rating Scale. SF-36 scores improved from a mean of 53.7 to a mean of 18.2. The percentage of patients with satisfactory (> or = 77) Lysholm scores increased from 5% preoperatively to 73%. In multivariable analyses, Worker's Compensation (p = 0.003), worse baseline physical functional status (p = 0.007), and Grade III-IV cartilage damage (p = 0.05) were associated with worse post-operative function. The outcome of APM is generally favorable. The extent of cartilage damage was confirmed as a correlate of poor outcome. However, Worker's Compensation and preoperative physical functional status had the greatest prognostic value and should be ascertained routinely in orthopedic outcome studies.


Correlates of knee pain among US adults with and without radiographic knee osteoarthritis.

We examined the associations of sociodemographic variables, health behaviors, health status and psychological well being with radiographic knee osteoarthritis (OA) and self-reported knee pain for 4056 US adults aged 45-74 years. Among persons with or without knee OA known correlates of radiographic knee OA (age, sex, race, obesity) were generally not associated with knee pain. Radiographic severity, psychological well being and health status were associated with knee pain, both among persons with and without radiographic knee OA, suggesting that nonradiographic correlates of self-reported knee pain are independent of whether a person has radiographic knee OA.


Treatment of knee osteoarthritis: relationship of clinical features of joint inflammation to the response to a nonsteroidal antiinflammatory drug or pure analgesic.

Our randomized double blinded comparison of acetaminophen versus analgesic and antiinflammatory doses of ibuprofen in the treatment of 182 subjects with knee osteoarthritis (OA) systematically evaluated soft tissue tenderness and joint swelling. Improvement in these signs of joint inflammation was associated with lessening of disability (p = 0.02), and reduction in rest pain (p = 0.07), but not with the drug treatment regimen. Thus, joint tenderness and swelling, presumptive evidence of synovitis, may not be a priori indications for use of an antiinflammatory drug, or predict greater responsiveness to treatment with an antiinflammatory drug than to a pure analgesic, in symptomatic treatment of patients with knee OA.


Interrater reliability of the tender point criterion for fibromyalgia.

The diagnosis fibromyalgia (FS) requires the existence of tender points, routinely identified by clinical examination. We evaluated the interrater reliability of digital (thumb) examination for tender points by comparison with dolorimeter examination, a procedure considered to measure accurately muscle tenderness. Subjects were 15 patients with varying rheumatological diagnoses and anatomically widespread pain. In a physician blinded procedure, 2 rheumatologists determined the tender point count by digital examination at 18 points, and the tender point threshold by dolorimeter at 12 points. A pain threshold of 4 kg/1.77 cm2 or less defined the presence of tender points under both methods. Results indicate (1) classification as FS vs other diagnosis using pain complaint and digital examination for tender points, was moderately reliable (kappa = 0.74, p < 0.005); (2) interrater agreement about presence/absence of tenderness at individual points was not significantly lowered by digital examination (kappa = 0.51, p < 0.0001) relative to dolorimetry (kappa = 0.62, p < 0.0001); however, (3) analyses on the 12 anatomical points that were common to both methods indicated that digital examination resulted in significantly more anatomical points being considered tender relative to dolorimetry. Our findings indicate that digital and dolorimeter measures are equally reliable, but have poor concurrent validity for defining tender points in FS. Implications of these findings for the classification of fibromyalgia are discussed.


Septic arthritis in patients with acquired immunodeficiency syndrome with human immunodeficiency virus infection.

We have evaluated the presence and characteristics of septic arthritis in intravenous (iv) drug users with human immunodeficiency virus (HIV) infection. Sixteen patients with both HIV infection and septic arthritis were studied and compared with 5 patients with septic arthritis but no HIV infection. Clinical profile, laboratory findings at the time of onset, localization, causative organisms, mean hospitalization time and presence of complications were the same in HIV positive and HIV negative patients. Staphylococcus aureus was the most commonly isolated organism in both groups. We conclude that septic arthritis in HIV infected iv drug users is not uncommon, it is produced by the same organisms and presents similar characteristics to the ones found in iv drug users without HIV infection. Therefore, the presence of HIV infection does not appear to modify the characteristics of septic arthritis.


Liver disease, erroneously attributed to methotrexate, in a patient with rheumatoid arthritis.

We describe a patient with rheumatoid arthritis and Felty's syndrome who developed evidence of hepatic dysfunction initially attributed to a short course of methotrexate therapy. He was subsequently found to have nodular regenerative hyperplasia.


Lymphadenopathy, oligoclonal T cell receptor rearrangement and systemic lupus erythematosus.

To investigate the cause of generalized lymphadenopathy in case of systemic lupus erythematosus (SLE), we performed a molecular genetic analysis of lymph node, peripheral blood mononuclear cell and bone marrow specimens with T cell receptor and immunoglobulin gene probes. Oligoclonal T cell receptor rearrangements were detected in the lymph node cells. The oligoclonal T cell expansion observed is the first such example reported in SLE, and may be indicative of an immune response to specific antigenic challenge. Alternatively, these changes may represent the earliest phases of a malignant process. Molecular genetic investigations in autoimmune disease such as SLE can provide opportunities to enhance our understanding of the underlying condition, or reveal unexpected abnormalities requiring further assessment.


The "shrinking lungs syndrome" in systemic lupus erythematosus--improvement with corticosteroid therapy.

A 35-year-old woman had a 13-year history of systemic lupus erythematosus (SLE) with recurrent flares since 1972 responding to corticosteroid therapy. In August, 1990 she presented with a 2-month history of dyspnea at rest, 4-pillow orthopnea and paroxysmal nocturnal dyspnea. Respiratory rate was 32-36/min, chest expansion 2 cm and crackles were present at the lung bases. On chest radiograph diaphragms were elevated. Pulmonary function tests (PFT) showed further reduction in lung volumes, maximum inspiratory pressures, maximum expiratory pressures and arterial blood gases. Ventilation/perfusion and gallium lung scans were normal. A diagnosis of "shrinking lungs syndrome" was made. Treatment with 40 mg of prednisone resulted in resolution of the patient's shortness of breath. PFT showed improvement in all variables. Corticosteroid therapy for acute "shrinking lungs syndrome" in active SLE can improve symptoms and pulmonary function.


Hypertrophic cardiomyopathy in systemic lupus erythematosus and "lupus-like" disease. Chance association? A report of 2 cases.

Two patients, both women, one with "lupus-like" disease, age 51 years, the other a 45-year-old with systemic lupus erythematosus (SLE), developed symptoms and echocardiographic signs of hypertrophic cardiomyopathy. One patient had a family history of sudden maternal death. Neither patient had a history of sustained hypertension and there were no significant valvular lesions detectable to account for the septal and ventricular hypertrophy. The association of SLE or any related condition with hypertrophic cardiomyopathy has not been recorded. In one patient the question of a hereditary cardiomyopathy remains a possibility. The diagnosis of the condition was based on clinical and echocardiographic grounds alone. No endomyocardial biopsies were performed.


Simultaneous occurrence of diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis in the same patient.

Diffuse idiopathic skeletal hyperostosis (DISH) frequently gives rise to some diagnostic confusion, as it may radiologically mimic ankylosing spondylitis (AS). A patient with features of DISH and AS is described and the literature is reviewed. The diagnostic value of sacroiliac computerized tomography is emphasized. The role of spinal mobility in the appearance of the enthesiophytes is discussed since our patient, who underwent a segmental fusion, presented different radiological features in the mobile segment and the fused region.


Magnetic resonance imaging assessment of sacroiliac joint involvement in Gaucher's disease.

A young woman with Gaucher's disease experienced acute pain in her right sacroiliac (SI) joint. Although pelvic radiographs and computed tomographic scan showed no significant change in the right SI joint, magnetic resonance imaging demonstrated an area of high signal intensity in the iliac part of the right SI joint, and a periosseous collection of blood. This skeletal location is rarely reported in Gaucher's disease; the mechanism of bone crisis is still controversial and our case suggests the occurrence of a bone infarct.


Spinal cord claudication from amyloid deposition.

We describe the clinical course of an 81-year-old woman who was evaluated for worsening symptomatology of spinal cord claudication. Diagnostic studies revealed mild lumbar canal stenosis at L3-4, severe stenosis at L4-5 with a myelogram-CT scan demonstrating a complete block at this level mainly a result of a hypertrophied ligamentum flavum. At surgery, the ligamentum was found to be thickened and to be causing severe compression of the dural tube. Pathologic studies of the excised ligamentum flavum revealed extensive amyloid protein deposition. The amyloid was not further classified with further medical evaluation and followup failing to identify any conditions associated with local or systemic amyloidosis.


Articular histoplasmosis.

Rheumatic manifestations of histoplasmosis are uncommon. Polyarthritis or arthralgias may occur as a part of a sensitization process in primary acute histoplasmosis. Infectious arthritis may accompany disseminated histoplasmosis or occur as solitary monoarthritis. Treatment of the latter traditionally consists of surgical excision followed by amphotericin B. Reports of clinical experience with the newer triazole compounds in treating articular histoplasmosis are lacking. We describe a patient with solitary monoarticular histoplasmosis of the knee who was successfully treated with oral fluconazole and required no surgical intervention. Specific issues that pertain to clinical presentation and management of articular histoplasmosis are discussed.


Detection of localized Salmonella infection by gallium-67 citrate scan.

Fifteen cases (9 males, 6 females, ages: 18-73 y/o) of salmonella bacteremia were referred for a Gallium-67 citrate (Ga-67) scan to detect the focal site(s) of salmonella infection. Among them, 8 were finally proved to have focal infection(s). Their underlying diseases were systemic lupus erythematous (SLE, 4 cases), malignancies (2 cases), immunocompromise (1 case) and unknown disease (1 case). The focal infections detected were septic arthritis in 6, soft tissue abscesses in 4 and lung abscesses in 2. This report suggests that Ga-67 scan is of great value in detection of localized salmonella infection.


[Kinetic studies of protein kinase A in rat liver during late sepsis].

The covalent modification of receptor proteins via phosphorylation and dephosphorylation is one of the principal mechanisms controlling carbohydrate metabolism and is known to be regulated by various protein kinases. Recent studies indicated that many hormones may exert their effects on cellular metabolism by regulating intracellular c-AMP levels and by activating a c-AMP dependent protein kinase, i.e., protein kinase A. The metabolic disturbances during sepsis are characterized by an initial hyperglycemia followed by a progressive hypoglycemia and a depletion of hepatic glycogen content. The latter is coupled with a slowdown in glycogenesis, an accelerated glycogenolysis, and a depression in gluconeogenesis in the liver. Since the liver is the major organ that regulates the homeostatic level of blood glucose, it is conceivable that the sepsis-induced glucose dyshomeostasis might be mediated by changes in protein kinase activity and the kinetic characteristics of enzymes. The present experiment was designed to study the correlation between protein kinase A and the pathophysiology of hepatic glucose dyshomeostasis during sepsis. Sepsis was induced in rats by cecal ligation and puncture (CLP). Late sepsis occurred 18 hours after CLP. Protein kinase A was extracted from the rat livers by acid precipitation and ammonium sulfate fractionation, and then partially purified by DEAE-cellulose. The results show that in the late sepsis, type-I protein kinase A (eluted at low ionic strength) activity was significantly decreased by 34-52% (P < 0.01). The kinetic parameters such as Vmax's for ATP, histone, and c-AMP were also significantly decreased from the control values of 6.1 +/- 0.9, 5.4 +/- 0.8, and 5.1 +/- 1.9 nmoles/mg.min. to 3.6 +/- 0.5, 2.8 +/- 0.3, and 2.5 +/- 0.5 nmoles/mg.min., respectively. Analysis using Hill's equation indicates that the S0.5 and n (Hill coefficient) values of the various substrates and activators for type-I protein kinase A remained unchanged. In the case of type-II protein kinase A (eluted at high ionic strength), the Vmax, S0.5, and n values for ATP, histone, and c-AMP were unchanged during late sepsis. The results of the present study indicate that the activities and kinetic characteristics of type I protein kinase A in rat liver are modified during late sepsis. Since protein kinase A is known to regulate glucose metabolism through adrenergic receptor mediation, these findings may have a pathophysiological significance in the understanding of hepatic glucose dyshomeostasis during sepsis.(ABSTRACT TRUNCATED AT 400 WORDS)


[Phagocytosis of the reticuloendothelial system in diabetes mellitus].

It has been assumed that patients with diabetes mellitus (DM), who are usually susceptible to bacterial infections, have a depression of the antibacterial defense mechanism. This study was undertaken to substantiate the hypothesis that phagocytosis of the reticuloendothelial system (RES) is depressed in diabetic patients. It is believed that intravenously injected colloidal suspensions whose particles are unable to pass through the capillary barrier will be phagocytized mainly by the reticuloendothelial cells in the liver and spleen. In the present study, the RES phagocytic index (RESPI) was measured in 48 subjects: 20 normal controls and 28 patients with DM. Measurements were based on the rate of disappearance (T1/2) of radioactivity in the heart (blood pooling) after rapid I.V. injection of 3mCi of Tc-99m phytate (2mg phytate). Using a gamma camera, sequential images of the liver and heart were obtained, and computer-generated time-activity curves were established. The T1/2 was then calculated. Our results revealed that the RESPI values in the DM group were significantly increased as compared to the normal control group (normal control = 4.60 +/- 1.01; DM = 6.78 +/- 3.83; P < 0.05). This prolonged half-disappearance time of blood radioactivity in diabetic patients is interpreted as a reflection of impaired phagocytotic efficiency in the reticuloendothelial system. The results of this preliminary study add support to the in vivo evidence explaining the increased susceptibility to infection in diabetic patients.


[A study of the satisfaction of clients with the home visiting service provided by public health nurses].

The purpose of this study is to explore the satisfaction of clients with the home visiting services provided by public health nurses. In addition, the related factors that influence this satisfaction are to be explored. A structured questionnaire was used for data collection. This study comprises 247 subjects who were chosen via distributive sampling, 222 questionnaires were completed for use. The completed percentage achieved 90%. Factors analysis was used to discern the satisfaction components. The contents of the client's satisfaction can be broken down into 5 major areas: (1) the assistance provided by home health services; (2) the professional capacities of the home-visiting nurses; (3) the disturbance caused by the home health services; (4) the home visiting nurses' capacity for instruction and reaction; (5) the autonomy of home health services. The results of this study indicate that the clients' satisfaction ratio achieves 89%. A stepwise multiple regression was used to analyze the related factors that influence the clients' satisfaction. We found that the most important variables were "the assistance provided by home-visiting services", "the necessity of home-visiting services", and "the variation in client diagnosis". The predictable variance of these three variables reaches 34.8%.


Pneumatosis cystoides intestinalis arising in jejunal diverticular disease: report of a case and a suggestion to its pathogenesis.

The occurrence of pneumatosis cystoides intestinalis (PCI) in the gastrointestinal tract is rare. Among the cases already documented in the English language literature, the association of PCI with jejunal diverticulosis has only been mentioned once or twice. We herein report a case of a 63-year-old woman who had both entities concurrently in a segment of the jejunum. What is important to note is the relationship of PCI to the diverticulosis and its possible pathogenesis. Through histological examination and review of related articles, we are convinced that a mechanical theory plays a pivotal role when both diseases occur in the same segment of intestine and are compounded by obstruction or impaired peristalsis. This finding, when properly applied to PCI in other settings, helps to resolve the pathogenesis of PCI and other related gas-filled cysts.


Osler-Weber-Rendu disease: a six generation family.

A Taiwanese family, with at least nine members in six generations has been affected with Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia. It is an autosomal dominant familial disease which involves systemic subepithelial fibrovascular dysplasia and manifests with telangiectasia or angiomas of the face, the palms, or the mucosa of the aerodigestive tract (such as the nose, lips, oral cavity, or stomach, etc.). The most common clinical symptom is recurrent epistaxis with/without upper gastrointestinal bleeding which may be resistant to the otolaryngologist's best efforts for control. Repeated bleeding marks the typical course of the disease. Epistaxis from hereditary hemorrhagic telangiectasias often requires a combination of therapeutic approaches. Carbon dioxide laser surgery was highly successful in decreasing postoperative morbidity and epistaxis in the four patients we treated.


Internal jugular phlebectasia.

Phlebectasia, defined as abnormal venous dilation, may occur in a number of different sites. Two cases with definite diagnosis of internal jugular phlebectasia were reported. The first case was a 6-year-old girl with a bulging mass on right neck for 3 years. Angiography and CT scan showed definite diagnosis, and the bulging mass was resected from the internal jugular vein (IJV). The second case was a 66-year-old female patient, also complained of a bulging mass on her right neck. Sonogram and CT scan also showed the same diagnosis. Because it did not bother the patient, she was just under close observation. From the three kinds of diagnostic modalities, we found sonography is an effective technique because of its clarity, safety and low cost.


[Neurogenic pulmonary edema: five cases report].

Five patients with neurogenic pulmonary edema (NPE) were reported. The edemas were caused by head injuries in four patients and by a craniotomy in the fifth. The onset of NPE was either acute (3 hours after injury) or was slow to develop (4 days later). Clinical symptoms included the sudden onset of coughing, tachypnea, tachycardia, and pink bubbly sputum. Moreover, the patients also suffered cyanosis, confusion, or respiratory failure. The distribution of the resulting pulmonary edema was diffuse in 4 cases and localized within a single lobe of the lung in 1 case. Treatment of the NPE included reducing intracranial pressure (glycerol), diuresis (furosemide and mannitol), narcotics (morphine, phenobarbital), and blocking the peripheral effect of sympathetic reflex activity (hydralazine, sodium nitroprusside). Mechanical ventilation support (CPU-1) in combination with controlled hyperventilation may also be necessary. The inability to correct hypoxemia without toxic levels of oxygen necessitates the use of PEEP (positive end-expiratory pressure, +5-10 cmH2O). Resolution of symptoms was noted 24 to 48 hours after treatment in 4 patients. Early diagnosis and intensive care of the pulmonary edema may have a significant bearing on the recovery of lung functions. Unfortunately, 4 of the patients failed to survive because of central nervous system failure. We therefore want to emphasize that NPE can cause secondary deterioration of neurological functions. In conclusion, when dealing with respiratory distress patients with CNS injuries, the possibility of additional damage from a NPE must be taken into consideration.


[Clinicopathological study on progressive hereditary nephritis: observations of ultrastructural lesions in the glomerular basement membrane].

Four boys and six girls with progressive hereditary nephritis were studied clinicopathologically. Renal biopsy was performed 16 times in ten cases. Mean age at renal biopsy was 7.3 years old (range 2 to 14 years old). The obtained results were as follows: (1) Montages of electron micrographs were prepared to complete one whole glomerulus. The length of the glomerular basement membrane (GBM) with the characteristic splitting of the lamina densa (Reticulation) was measured and expressed as a percentage of the total length of the GBM. The range of the percentage of the GBM with Reticulation was from 2 to 43% (13.4 +/- 10.0%, mean +/- SD, n = 16). In 4 cases of the 5 cases performed serial renal biopsy, the percentage of the GBM with Reticulation at the 2nd biopsy increased compared with the 1st one. (2) Protein excretion in the urine, serum albumin, alpha 2-globulin, fibrinogen and total cholesterol showed the correlation with the percentage of the GBM with Reticulation. (3) Incomplete ruptures (deep invasion of the epithelial cells into the thickened GBM with Reticulation) were observed. Those suggested that the GBM became fragile associated with the expansion of Reticulation and finally ruptured. Gaps of the GBM were observed 0 to 3 per in one glomerulus (0 to 1.87 per 1mm GBM) and the serial biopsies showed an increase in the number of the gaps as time passed. (4) This study showed the increase in factors activating the blood coagulation such as total cholesterol and fibrinogen, with the expansion of the GBM with Reticulation. And in a nephrotic case, fibrin strands were observed in the glomerular capillary loops and in the GBM. These findings suggest that the activation of the blood coagulation plays a role for the damage of the glomeruli in progressive hereditary nephritis.


[Echocardiographic assessment of cardiac function in the children of chronic renal failure with cardiomegary].

Five children (four boys and one girl) with chronic renal failure (CRF) developed congestive heart failure 0.5 to 11 years after the onset of the disease. Their ages were from 4 to 13 years old. They noticed tachypnea, tachycardia, cough, chest anxiety, general fatigue and their chest X-rays showed cardiomegaly with cardio-thoracic ratio (CTR) of from 55 to 63% and pulmonary congestion. Their echocardiograms showed no cardiomuscular hypertrophy, but the dilatation of left ventricular diastolic diameter (LVDd), and the decreased ejection fraction (EF) were observed. They were treated with water restriction, antihypertensive agents, cardiotonics and dialysis. Their clinical symptoms improved promptly, but their cardiomegary and echocardiographic findings improved gradually. The causes of heart failure in these patients seemed to be due to uremia, fluid overload and hypertension. The echocardiographic examination was useful for the management of the children with CRF in heart failure.


[Clinical effects of six-month short time biofiltration].

The clinical effects of six-month short time biofiltration (SBF) were evaluated using a B-A-B' study (B, B': conventional bicarbonate hemodialysis; CBHD, A:SBF) in ten patients maintained on CBHD three times a week. An F80 hemodiafilter (1.9 m2, polysulfone, Fresenius) was used. In addition to routine clinical parameters for a patient on regular dialysis treatment, plasma von Willebrand factor antigen (vWF) (an index of stimulation of vascular endothelium), and the methylguanidine/creatinine ratio (MG/Cr) and malondialdehide (MDA) (indices of the levels of oxygen radicals), were evaluated. Nine patients completed the study, one patient dropping out at the 12th week of A because of muscle cramps during SBF. The treatment time was 2 hours in six cases and 2.5 hours in three cases. The mean blood flow rate was 280 +/- 42 (SD) minutes. Using the urea kinetics model, the mean KT/V was 1.26 +/- 0.28, and the mean protein catabolic rate was 1.22 +/- 0.18 g/kg body weight/day at the end of A. No change in ultrafiltration, blood pressure, cardiac function (assessed by echocardiography), CTR, human atrial natriuretic peptide, total protein, albumin, uric acid, serum creatinine, sodium, calcium, inorganic phosphorus, vWF, or MDA was found between each period. Blood urea nitrogen, c-PTH, and MG/Cr increased during the A period. Serum magnesium and beta-2 microglobulin decreased during the A period. Blood gas results, on the whole, did not change. In a patients, however, acidosis gradually developed. An increase in substitution fluid from 5 L/session to 7.5 L/session improved the acid-base balance in that patient. In conclusion, SBF is as effective as CBHD in removing small molecules and maintaining cardiocirculatory status, and is superior to CBHD in removing beta 2-microglobulin and is less stimulative to the endothelium than CBHD.


[Effect of weight loss on the reduction of blood pressure in obesity hypertension--hyperinsulinemia and renal sodium retention].

The role of insulin and dopamine on blood pressure and renal sodium excretion was evaluated in 10 obese hypertensive patients. Essential hypertensive subjects (age 49.7 +/- 7.7) with at least 26.0kg/m2 obesity were hospitalized and a 2000k cal diet for 7 days (control periods) followed by a 800 k cal for 21 days were given. Salt intake was maintained at 10 g/day throughout this study. Mean blood pressure (MBP), plasma insulin (IRI), urinary dopamine and fractional excretion of sodium (FENa) were measured in both diet periods. Body mass index significantly decreased from 31.6 +/- 4.6kg/m2 to 28.6 +/- 4.1 kg/m2 after weight reduction (P < 0.001). MBP significantly lowered from 112.8 +/- 14.1 mmHg to 100.4 +/- 12.4 mmHg (P < 0.01) and IRI from 9.11 +/- 5.0 microU/ml to 6.3 +/- 5.5 microU/ml (P < 0.001) after weight loss. We observed a significant correlationship between delta MBP and delta IRI (r = 0.754, P < 0.01). Also, we observed a significant correlationship between delta MBP and delta FENa (r = -0.835, P < 0.01). A significant relationship was observed between urinary excretion of sodium and urinary excretion of dopamine (r = 0.507, P < 0.05). We concluded that sodium retention and increase of sympathetic nervous activity by hyperinsulinemia might play an important role of hypertension, and blood pressure reduction by weight loss resulted from decreased insulin and increased excretion of sodium in obesity hypertension.


[A diabetic patient with empty sella syndrome accompanied by stimulated guanidinoacetic acid metabolism].

Since urinary guanidinoacetic acid (GAA) derives from the kidneys, its detection is suggested to be associated with renal disease. We have been making a practice of investigating renal GAA production in diabetic patients, using a citrulline/creatine loading test. We noted a marked increase in urinary GAA excretion in 1 patient. Since GAA-synthesis is hormonally regulated, we made a through investigation of endocrine function in this patient. She was a 58-year-old woman with a 15-year history of diabetes mellitus, proliferative diabetic retinopathy, and negative microalbuminuria. There was a high plasma GH level and urinary 17-KS analysis revealed an increase in the adrenal androgen-derived fractions. Based on the X-ray finding of ballooning of the sella turcica and the MRI data, empty sella syndrome was diagnosed. It was suggested that stimulated anabolic hormone release had accelerated renal nitrogen metabolism and induced aggravation of her retinopathy. The findings in this patient implied the involvement of hormones in the development of diabetic complications.


[A case of Bufferin induced acute interstitial nephritis--analysis of immune cells and cytokine].

This paper describes a case report of acute interstitial nephritis associated with Bufferin. A 15-year-old girl were referred to our hospital due to fever and renal dysfunction. Laboratory findings showed elevation of serum BUN and creatinine, and increased urinary beta 2-MG excreation. Light microscopic findings of her renal biopsy specimen revealed edema and numerous inflammatory cells in the interstitium, and minor alterations in glomeruli. The interstitial infiltrates consisted mainly of T cells and also monocytes/macrophages. Interstitial cells were labelled with antibodies to interleukin (IL)-1 and tumor necrose factor (TNF). Bufferin was positive by lymphocyte stimulation test. Thus, we considered that this drug was causative in this case. This observation suggests the participation of cell-mediated immune injury in drug induced acute interstitial nephritis.


[Effects of growth factors on proliferation of cultured human peritoneal mesothelial cells].

Loss of ultrafiltration during continuous ambulatory peritoneal dialysis (CAPD) is often caused by the structural peritoneal membrane alteration, namely the disappearance of mesothelial cells and the proliferation of peritoneal collagen fibers. The interleukin hypothesis has been proposed to explain the etiology of peritoneal fibrosis. The CAPD procedure has been shown to induce macrophages and lymphocytes in the peritoneum, resulting in the production of interleukin-1 (IL-1) and interferon-gamma (IFN-gamma), which may be promote to the development of peritoneal fibrosis. On the other hand, the mesothelial defect can be rapidly restored by proliferation of mesothelial cells implanted on the wound surface. In this study, we demonstrated that IL-1 beta, IFN-gamma, epidermal growth factor (EGF) and platelet derived growth factor (PDGF) enhance to the growth of cultured human peritoneal mesothelial (CHPM) cells. The cell cultures were derived from surgically removed omentum using the enzymatic disaggregation method. CHPM cells were cultured with Ham's F-12 medium containing 10% FCS up to third generation. At a concentration of 1x10(4) cells/well were cultured with various concentrations of IL-1 beta, IFN-gamma, EGF, PDGF and IL-6. [3H] TdR (37MBq/well) was added to the cultures during the last 12hr of the 48hr culture period and then radioactivity was measured to determine the uptake of [3H] TdR. It was shown that IL-1 beta, IFN-gamma, EGF and PDGF induced the proliferation of CHPM cells in a dose dependent manner when cultured in medium containing 3% FCS.(ABSTRACT TRUNCATED AT 250 WORDS)


[Studies of the analysis of urinary proteins from children with renal diseases by reversed-phase high performance liquid chromatography].

In order to analyze urinary proteins from patients with various renal diseases, a reversed-phase high performance liquid chromatography (HPLC) with IPG PACK ODS column packed with polyporous glass was used. The reproducibility of standard proteins was good. The results by this method correlated well with those by radioimmunoassay or laser nephelometry, precolumn procedure needed the centrifugation only. The reversed-phase HPLC was superior to the other HPLC methods in the analysis of urinary proteins for its simplicity and high sensitivity. The peaks of both alpha 1-acid glycoprotein (alpha 1-AGP) and human serum albumin (HSA) in the chromatogram was regarded as the marker of renal damage. Urinary alpha 1-AGP/HSA ratio was calculated after measuring these two peak areas. As a result, it was significantly higher in the urine from patients with various glomerulonephritis (GN) than in those from healthy children. In the patients with postural proteinuria, it was the same level as that in healthy children. These date suggest that the urinary alpha 1-AGP/HSA ratio would be a beneficial indicator to find out the patients with GN from among children with proteinuria. Furthermore, it seems that this method is suitable for use in routine screening of renal diseases for its simplicity and speed.