[Surgical treatment of aortic root abscesses using a hand-made valved xenopericardial conduit].

A case is described in which a new treatment was taken to eradicate an aortic root abscess in a 56-year-old man with aortic prosthetic valve endocarditis. Debridement of all apparently infected tissue created left ventricular-aortic discontinuity, involving the orifice of the right coronary artery. A conduit of a diameter of 23 mm was made by hand with a glutaraldehyde preserved xenopericardial graft. A 21 mm St. Jude Medical prosthetic valve was sewn in it at 2 cm to its edge. The hand-made valved conduit was used to reconstruct the left ventricular outflow tract and aortic root. A saphenous vein graft was anastomosed end-to-side to the right coronary arterial system and to the conduit distal to the prosthetic valve. The aortography revealed no aortic regurgitation nor abnormalities of the conduit, such as aneurysm formation, and the coronary arteriography showed a functioning graft 5 months after surgery.


[An emergency surgical case of double aortic arch with hemoptysis].

A 78-year-old man was admitted because of hemoptysis. CT and aortogram revealed double aortic arch. Bronchofiberscopy revealed intratracheal hemorrhage which was associated with right aortic arch. An emergency operation was performed to prevent massive intra-tracheal bleeding. The patient underwent ligation of the right aortic arch through median sternotomy. After operation, hemoptysis disappeared and the postoperative course was uneventful. Surgical cases of double aortic arch are rare, especially with critical hemoptysis in aged patients.


[A case of hypertrophic pulmonary osteoarthropathy caused by adenocarcinoma of the lung].

A 58 year old housewife with tumor shadow in the right upper lung field on the chest X-ray was admitted. Marked swelling and severe arthralgia of both extremities and soft tissue clubbing of the fingers had been presented for two years prior to admission. The radiographs and bone scintigrams indicated proliferating periostitis along the long bones. Bronchofiberscope showed the obstruction of B2a of the right bronchus but the histological diagnosis was not established. Serum level of CEA and IAP were found to be high. Soon after the right upper lobectomy, arthralgia was significantly improved. The histological evaluation revealed a well differentiated adenocarcinoma of a primary lung cancer without mediastinal lymph node metastasis. Within 4 months the serum level of CEA and IAP normalized, the clubbing and the periosteal changes of the bones regressed.


[The platelet aggregation inhibiting activity in human placenta--study on the ADP degrading activity of human placental villi].

We studied the platelet aggregation inhibiting activity and ADP degrading activity of human placental villi (tissue culture supernatant) and brush border membrane vesicles (BBMV) and obtained the following results. 1. There existed a platelet aggregation inhibiting activity in tissue culture supernatant of villi (S-villi) but not in that of decidua or amnion. The S-villi inhibited the platelet aggregation induced by ADP, but not that induced by collagen, arachidonic acid or ristocetin. And, there was also ADP degrading activity (ADPase activity) in the S-villi. ADP was quickly degraded by S-villi. When ADP was preincubated with S-villi, the platelet aggregation induced by ADP was completely lost. 2. There was very strong platelet aggregation inhibiting activity in placental BBMV. The BBMV almost completely inhibited the platelet aggregation induced by ADP, collagen, arachidonic acid and ristocetin. And there was very strong ADP degrading activity in the placental BBMV. ADP was quickly degraded by BBMV. When ADP was preincubated with BBMV, the platelet aggregation induced by ADP was completely lost. 3. The enzymatic character (heat stability, enzymatic kinetics, Ca++ dependency and pH dependency) of ADP degrading activity in BBMV was very similar to that in S-villi. 4. The ADP degrading activity of both S-villi and solubilized BBMV were fractionated by anion exchange column chromatography and gel filtration column chromatography in similar patterns, and it was shown that ADP degrading substance of both S-villi and solubilized BBMV had a molecular weight of about 60K.


[Hematological values in fetal blood by cordocentesis].

Reference ranges for four hematological parameters--hemoglobin, hematocrit, white blood cell and platelet count--in each gestation were established from values for fetal blood samples obtained by cordocentesis from 72 pregnancies at 16-39 weeks gestation. These 72 fetuses turned out as normal or single malformations which should not affect fetal hematological values. Significant correlations were observed between hemoglobin, hematocrit and platelet counts and the number of weeks of gestation. No correlation was found between the white blood cell count and gestational age. Fetal anemia (hematocrit was below the lower limit of the 95% confidence interval) was found in 18 (7%) of all the fetuses that underwent cordocentesis, including nonimmune hydrops fetalis (8 cases), Rh isoimmunization (4 cases), twin-to-twin transfusion syndrome (3 cases), trisomy 18 (2 cases) and autoimmune thrombocytopenia (1 case). Of 26 hydropic fetuses, 8 (31%) were anemic. The prognosis of those fetuses depended on either the gestational age or the severity of the fetal anemia. Our results are useful in diagnosing fetal hematological disorders and to make decisions for fetal therapy.


[A biochemical study on the effects of interleukin-6 for premature rupture of membranes].

Chorioamnionitis was thought to be a cause of premature rupture of membranes (PROM). Recently it has been accepted that IL-6 is one of the important cytokines in inflammation. To investigate the correlation between PROM and IL-6, IL-6 production in chorionic cells and amniotic cells was examined. Moreover, the response of these cells to IL-6 was also examined. The results were as follows. 1. Chorionic cells and amniotic cells obtained from human membranes were cultured. 2. Comparing IL-6 production, chorionic cells produced a larger amount of IL-6 (425pg/ml/24 hrs) than amniotic cells (4pg/ml/24 hrs). 3. IL-1 treatment (10U/ml) caused a significant increase in IL-6 release from both chorionic and amniotic cells (43.2ng/ml/24hrs vs. 50.3pg/ml/24hrs, respectively). 4. Lipopolysaccharide (LPS) (10 micrograms/ml) stimulated the release of IL-6 in chorionic cells, but did not affect it in amniotic cells at all. 5. By staining with F actin, it was demonstrated that IL-6 expanded the cellular gap in amniotic cells. 6. After amniotic cells were co-cultured with chorionic cells, IL-1 treatment caused actin-polymerization in amniotic cells. These results suggest that chorionic cells produce a large amount of IL-6 as a result of stimulation by IL-1 or LPS, and the IL-6 produced constricts the amniotic cells. The phenomena may participate in the mechanism of PROM.


[Prolactin disorders in patients with habitual abortion].

To evaluate the significance of prolactin (PRL) disorders as one of the etiologic factors in habitual abortion, one hundred and six couples with a history of recurrent spontaneous abortion were assessed clinically and endocrinologically. A high rate of PRL disorders (eight patients with hyperprolactinemia and 31 patients with occulted hyperprolactinemia) was observed (36.8%) in habitual aborters, and only nine of these patients showed clinically detectable luteal insufficiency. These patients who had PRL disorders without luteal insufficiency were further analyzed with immunological examinations. Immunological evaluations revealed that there was no significant difference between the subpopulations of peripheral blood lymphocytes (PBL) in patients with PRL disorders and normal controls while the PHA-stimulated blastogenic activity of PBL and ConA-induced IL-2 synthesis by PBL was slightly suppressed as compared with that of normal controls. And the incidence of HLA sharing in couples with PRL disorders was demonstrated to be higher than that of the normal control couples without abortion. Patients with PRL disorders without impaired corpus luteum function were treated with bromocriptine only, and this therapy was very effective in maintaining pregnancy. The results of this study have allowed us to suggest that PRL disorders might be some of the etiologies in the so called "unexplained" habitual abortion.


[Urinary 11-dehydrothromboxane B2 and 6-keto-prostaglandin F1 alpha in normal pregnant women and in women complicated with pregnancy-induced hypertension].

In normal pregnancy, increased production of platelet thromboxane A2(TXA2) parallels increased biosynthesis of vascular prostacyclin (PGI2). An imbalance in the formation of these prostaglandins is believed to be associated with the pathogenesis of pregnancy-induced hypertension (PIH). Recent evidence suggested that aspirin in low doses was effective in reducing the incidence of PIH, by selective inhibition of platelet-derived TXA2 biosynthesis. In this communication, we determined the urinary 11-dehydro TXB2 and 6-keto-PGF1 alpha, which are major metabolites of TXA2 and PGI2, respectively, from early to late pregnancy of normal pregnant women and of women complicated with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha decreased significantly from as early as 10wks of gestation when compared with that in non-pregnant controls (1.43 +/- 0.15 vs 1.99 +/- 0.13: Mean +/- SEM, p less than 0.05), and increased in later pregnancy to the control values at term. No significant difference was found in the excretion of 11-dehydro TXB2 between normal pregnant women and women with PIH. In contrast, urinary excretion of 6-keto-PGF1 alpha decreased in women with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha increased significantly as compared with that of pregnant controls. These results demonstrated that disturbed production of vascular PGI2 may be the primary cause of PIH, and affect the vascular responsiveness to pressor inducers such as angiotensin II.


[Tryptophan and its metabolite concentrations in human plasma during the perinatal period].

The concentration of tryptophan (free and protein bound) and its metabolites in the plasma of the maternal vein and in the umbilical vein, umbilical artery and neonatal vein were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in the umbilical vein and artery were significantly higher than those in the maternal vein. Especially the 3-OHAA level in umbilical blood was approximately 50 times as high as that in maternal blood. The concentration of total tryptophan in the plasma of the neonatal vein showed a marked decrease at one day after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in the plasma of the neonatal vein. In the blood, ratios of free to total tryptophan and kynurenine were kept at a constant level throughout the perinatal period. In conclusion, the present study suggests that tryptophan metabolism may play an important role in fetal development.


[Clinical study of post-term pregnancy].

One hundred fourteen cases of post term pregnancy were clinically analyzed and classified. 1. In case of primipara, the duration of labor was longer and the frequency of prolonged labor (greater than 24 hours) was higher than that of the same number of cases of term delivery at 39 weeks. 2. The main cause of prolonged labor was weak pains. 3. The mean newborn umbilical artery pH in prolonged labor cases was not lower than that in other cases. 4. The cases of post-term pregnancy were classified into 4 groups and compared each other in several respects. Group I: prolonged labor(-), fetal distress(-), vaginal delivery. Group II: prolonged labor(-), fetal distress(+), vaginal delivery. Group III: prolonged labor(-), fetal distress(+), cesarean section. Group IV: prolonged labor(+). 1) The length of the fundus uteri: Group III: minimum after 31 weeks: Group IV: maximum after 35 weeks. 2) The body weight of the newborn and the weight of the placenta: Group III: minimum: Group IV: maximum. 3) The titer of E3 in urine: Group III: obviously low. 4) The frequency of Clifford's sign: Group III: high frequency of meconium staining. Cases of post-term pregnancy were composed of several groups with different clinical features.


[A prospective study of psychosomatic reaction to hysterectomy].

Psychosomatic reaction to hysterectomy was prospectively studied by means of psychological tests and a questionnaire. One hundred and twenty patients who had simple hysterectomy were examined before and as long as one year after operation. The mean score for A-state, a state anxiety scale, was high before operation and rapidly declined postoperatively. SRQ-D and CMI, which represent depressive and neurotic states, respectively, showed rather high scores before and 2 weeks after operation. Mean scores in these psychological tests declined to a plateau within 6 months after operation, and there were less psychological and physiological symptoms and there was improved physical activity, showing that most patients can over come psychosomatic problems caused by hysterectomy. A close correlation was observed between the results of psychological tests and the number of psychological symptoms. Forty patients with a high SRQ-D score showed abnormality in other scales. Psychosomatic disorders associated with hysterectomy are characterized by various symptoms but mainly by a depressive state. High SRQ-D patients were divided into three subgroups: A) the SRQ-D score is constantly high, B) the SRQ-D is high for the first several weeks, and C) the score increased after discharge. Patients in each subgroup showed signs of a characteristic personality. These results show the presence of a different psychosomatic approach to the patients personally.


[Mass-screening for ovarian cancer by means of transvaginal ultrasonography].

Since April, 1989 in Aomori Prefecture, mass-screening for ovarian cancer by means of transvaginal ultrasonography has been performed in a mass-screening car at the same time mass-screening for uterine cervical cancer. Subjects for this screening were self referred asymptomatic women 30 years of age or older. Real time ultrasonography was performed with a 5-MHz endovaginal transducer 5 sections for scanning were established by means of a transvaginal probe and all ultrasonic pictures obtained were recorded with an 8mm VTR. For women with abnormal ultrasonic findings, such as an ovary (tumor) over 30mm in size and massive ascites, a second screening or accurate examination was performed by retransvaginal ultrasonography, CT-scan, MRI and a combination assay of tumor markers. The results were as follows: The time required for the first screening, including bimanual examination, collection of Pap smear and ultrasonic examination, was about 60-70 seconds. The total number of screened women was 15,282, and 838 (5.5%) of them needed to receive the follow-up examinations. Laparotomy has been done for 48 women to date and 2 women were found to have premalignant and malignant ovarian tumors.


[Immunohistochemical study on the expression of epidermal growth factor receptor (EGF-R) in invasive cervical cancer of the uterus].

We have investigated the expression of epidermal growth factor receptor (EGF-R) in invasive cervical cancer tissue of the uterus to determine whether there is a relationship between the expression of EGF-R and lymph node metastasis. Frozen sections of surgical specimens from twenty patients with invasive cervical cancer were immunohistochemically stained by the alkalinephosphatase anti-alkalinephosphatase method. The monoclonal antibody 528 we employed reacts with the receptor binding epitope within the EGF molecule, indicating that monoclonal antibody 528 is competitive with ligands such as EGF. Immunohistochemical staining was carried out before and after dissociation of ligands from the cellular surface of the tumor by acid treatment. However, the staining was resulted in no difference between before and after acid treatment. Consequently, the expression of EGF-R was detected in all cancer tissues as well in some normal tissue such as basal cell layers of epidermis. The expression of EGF-R was related inversely with lymph node metastasis by Wilcoxon rank sum test (p less than 0.05). These findings suggest that the expression of EGF-R in cervical cancer does not always lead to tumor growth or tumor invasion, although it does in some types of cancer.


[An early detection of the recurrence of serous cystadenocarcinoma of the ovary with the tumor marker CA125 levels].

We studied whether or not, and to what extent, it was possible to predict the recurrence of serous cystadenocarcinoma of the ovary by means of the tumor marker CA125 levels, in 35 treated cases of ovarian serous cystadenocarcinoma. The relationship between the change in CA125 levels and the frequency of recurrence was examined in two groups (recurrent group and non-recurrent group). When CA125 levels over 35U/ml were defined as positive for recurrence, the true positive rate was 22/23 in the recurrent group, and 0 in the non-recurrent group. When this cut-off level was lowered to 30U/ml, and then 25U/ml, the false positive rate in the non-recurrent group was increased to 1/12 and 4/12, respectively. A three-serial increase in CA125 levels was observed at the onset of recurrent cases including two cases with CA125 levels under 35U/ml, while it was not detected in any in the non-recurrent group. Analysis of the CA125 level increase pattern with a non-linear model showed that recurrence could be detected before the CA125 level reached 100U/ml in 13/19 (68.4%) cases if the interval between CA125 measurements was one mouth, and in 17/19 (89.5%) cases if the interval was two weeks. These results suggest that possibility that recurrence can be detected early.


[Production of CA125 in cell lines derived from human ovarian carcinoma: in relation to the cell cycle].

The association of the production of CA125 with the cell cycle was investigated in two cell lines derived from human ovarian cancer, one from a serous cystadenocarcinoma (HTOA) and the other from a mucinous cystadenocarcinoma (RMUG-s). HTOA and RMUG-s cells secreted CA125 at about 50 and 30U/ml/10(5) cell/24hr, respectively, in the logarithmic growth phase and at about 75 and 100U/ml/10(5) cell/24hr in the steady phase. Analysis by FCM revealed that cultures of both cell lines cultured for 7 days contained more cells in the G0/G1 phase and less cells in the S phase than those cultured for 3 days. The positive rate of immunologically stained DNA polymerase alpha was 31% in HTOA cells and 39% in RMUG-s cells after cultivation of the cells for 3 days. The addition of EGF at 0.01, 0.1 or 1.0nM did not affect the production of CA125 in HTOA or RMUG-s cells while the addition of NaBT at 1, 3 and 5mM raised production in both cell lines as the dose rose. With RMUG-s cells, the addition of EGF at 0.01nM to the culture media accelerated both logarithmic and steady phase growth without a significant change in the production of CA125. In contrast, the addition of NaBT at 1mM suppressed growth, but tended to increase the production of CA125 per cell. With the effect of EGF on the cell cycle of both cell lines, cells in the S phase increased by about 20% as compared with the control, 48 hours after its addition at 0.01nM. In contrast, after cultivation for 48 hours in the presence of 1mM NaBT, cells in the S phase were decreased while those in the G0/G1 phase increased. The results presented above suggested the possibility that some factors other than the cell cycle were involved in the production of CA125. There also is close correlation between cells in the G0/G1 phase and the production of CA125 in the culture of human ovarian cancer cells.


[Stimulatory effects of follicular stimulating hormone on the proliferation of ovarian cancer cell line in vitro and in vivo].

The present study was designed to determine the effects of follicular stimulating hormone (FSH) on the proliferation of the human ovarian cancer cell line (HRA line) in vitro and in vivo. The results showed: 1) The number of cells and 3H-thymidine uptake significantly increased after FSH treatment, but were suppressed by Buserelin (number of cells: 2.5 +/- 0.4 [con] vs 13.8 +/- 1.7 [FSH] vs 3.0 +/- 0.2 [FSH+GnRHa] x 10(4)/ml, uptake: 1,272.0 +/- 51.5 [con] vs 4,183.4 +/- 114.1 [FSH] vs 885.0 +/- 177.0 [FSH+GnRHa]cpm/10(5) variable cell mean +/- SD, p less than 0.05). 2) FSH increased the proportion of the cells in the S phase but decreased the cells in G0/G1 phase (S: 42.1 +/- 0.72 [con] vs 61.7 +/- 0.5 [FSH], G0/G1: 53.8 +/- 0.4 [con] vs 35.5 +/- 0.6 [FSH]% mean +/- SD, p less than 0.01, t-test). 3) Cyclic adenosine monophosphate (cAMP) production by HRA cells was significantly increased by cholera toxin (CTX), but not by FSH (1.29 +/- 0.72 [con] vs 2.05 +/- 0.21 [FSH] vs 16.2 +/- 2.28 [CTX]nM mean +/- SD p less than 0.001), suggesting that FSH has no effects on the adenylate cyclase system in the cell line. 4) FSH and GnRHa receptors were identified in HRA cells, and the number of the receptors was significantly decreased by Buserelin treatment (426.0 +/- 6.8 vs 98.6 +/- 12.3 sites/cell mean +/- SD, p less than 0.05, t-test).(ABSTRACT TRUNCATED AT 250 WORDS)


[A radiological measurements of growing hip joint in 4,000 normal children].

Roentgenograms of 4,000 hip joints of normal children were analyzed. The indices we used were as follows, the YO-value as the standard of growth (half of the distance between the both Y-cartilages), the CO-value as an index of lateralization (the distance between the center line of the pelvis and the center point of the head of the femur), the EO-value as the index of formation of the acetabulum (the distance between the center line of the pelvis and the tip of the acetabular tegmen), epiphyseal height (A), epiphyseal width (B), the alpha-angle, the CE-angle, the Sharp angle etc. The evaluation method we used consisted basically of comparisons made among values indicating length and by which the pelvis showed nearly proportional growth. The correlation coefficient among the YO-, CO-, and EO-values was extremely good. Accordingly, those indices are considered useful for the prognosis of congenital hip dislocation.


Metachondromatosis: a report of two cases in a family.

We have described a 10-year-old Japanese boy and his father with metachondromatosis characterized by multiple exostoses, enchondromas, and periarticular calcification or ossification and reviewed the literature on this condition. The boy developed bilateral epiphyseal changes in the hips mimicking Perthes' disease. These cases are the first Japanese individuals with this disorder. The natural history and the associated disorders of metachondromatosis are also discussed in this paper. Metachondromatosis is an inherited skeletal dysplasia characterized by multiple cartilaginous exostoses, multiple enchondromas, and periarticular calcification or ossification. The mode of inheritance of the disease is autosomal dominant. In 1971, Maroteaux first described the disorder in 6 patients of 2 kindreds. Since then, 22 cases have been reported. However, no Japanese patient with this disorder has been described to date. We herein report a Japanese boy and his father with this rare bone dysplasia. The boy developed bilateral epiphyseal lesions in the femoral heads mimicking Perthes' disease.


Antitumor effect of thermosensitive CDDP-liposomes on human osteosarcoma cells in culture.

We have administered cis-diamminedichloroplatinum (II) (CDDP) containing thermosensitive liposome and simultaneous hyperthermia into human osteosarcoma cells (OST) and studied the antitumor effects. Experiments were conducted under the following three different culture conditions as follows, (1) drug treatment alone, (2) hyperthermia after drug treatment, and (3) simultaneous hyperthermia and drug treatment. Antitumor effects were estimated by inhibition of DNA synthesis and decrease in cell growth rates. The antitumor action of simultaneous hyperthermia and drug treatments was the most dominant and synergistic among three experimental conditions. Accumulation of cellular platinum from thermosensitive CDDP-liposomes was markedly enhanced by hyperthermia. Flow cytometric analysis of the cell cycle indicated that CDDP-liposomes only under the simultaneous application of hyperthermia released free CDDP, and evoked cell accumulation in S and G 2/M phase. The results suggested that thermosensitive CDDP-liposomes were not taken up into cells by endocytosis, and released free CDDP into culture media under hyperthermia at 42 degrees C. From these, we have concluded that administration of thermosensitive CDDP-liposomes and simultaneous local hyperthermia could be a promising method for the treatment of osteosarcoma especially in the extremities.


[Three-dimensional motion analysis of the wrist using two-directional radiography, with special reference to the motion of the scaphoid].

To clarify the motion of the scaphoid, which exhibits unique movement among the carpal bones, three-dimensional motion analysis of the wrist was conducted. Three fresh-frozen cadavers were thawed, and three-dimensional measurement was carried out using two-directional radiography. Conventional two-dimensional measurement with unidirectional radiography was also carried out for comparison with the three-dimensional measurement. After measurement, the cadavers were dissected and the anatomical findings were correlated with results of measurement. During flexion-extension movement of the wrist, the scaphoid showed flexion-extension movement accompanied by rotation around the longitudinal axis. In radio-ulnar flexion of the wrist, the scaphoid did not exhibit flexion-extension movement in such a way as reported previously, but showed rotation around the longitudinal axis. These results and the anatomical findings suggest that the rotation around the longitudinal axis in both flexion-extension movement and radio-ulnar flexion is the movement along the articular surface of the capitate.


[An experimental study on mechanism of cruciate ligament rupture especially on the effect of mechanical property and tensile speed].

Patterns of rupture of the anterior cruciate ligament of the knee are most probably determined by mechanical factors. An experimental study was designed to determine patterns of rupture of the anterior cruciate ligament in immature (young) and fully mature (adult) pig models. Two different methods were used to test disruption forces in young and adult pig knee specimens: quasi-static tension at three different rates using the Instron testing instrument (1000), and impact loading using a specially designed machine. A total of 118 pig test knees was studied. Greater rupture force was required in the adult pigs than in the young pigs. In addition, rupture force was higher with impact loading test than with quasi-static tensile test. In the young pigs, avulsion fracture occurred most commonly in both tests. In the adult pigs, however, mid-substance disruption occurred with quasi-static tensile test and bony avulsion occurred with impact loading test. Patterns of disruption in pig models varies with the relative maturity of the animals tested and mode of force application. A possible explanation for this is the relative strength of the bone and ligament in animals of varied maturity.


Stereoscopic vascular architecture of the adult rat femoral head.

We studied the micro-architecture of the rat femoral head using a corroding casting method described by Murakami in comparison with haematoxylin-eosin preparation and transparent preparation. Stereoscopic architecture of the microvasculature in the femoral head was finely demonstrated. Vessels in the metaphysis and the epiphysis were aggregated to form a lobular-like structure. The lobules were interconnected with each other by a few capillaries. A bigger vessel probably corresponding to a drainage vein was seen crossing the growth plate. Loop formations, from simple hairpin-like loop to a more complex loop with a glomerular-like aspect, were demonstrated in the metaphysis underlying the growth plate as well as in the articular surface of the epiphysis.


[Immunohistochemical localization of interleukin-1 and lipopolysaccharide (LPS) of experimental arthritis in the ankles of rats immunized with LPS extracted from Escherichia coli].

Sprague Dawley (SD) rats were immunized by subcutaneous injections with heat-killed E. coli 0:14 and lipopolysaccharide (LPS) extracted from E. coli for 15, 29 and 39 weeks which induced arthritis in the ankle. Localization of interleukin-1 (IL-1) and LPS in the ankle joints were investigated immunohistochemically. Serum IgM rheumatoid factor-like substance (RFLS) and anti-LPS IgM were detected by enzyme-linked immunosorbent assay (ELISA). Rats immunized with LPS for 39 weeks developed synovial lining cell hyperplasia in 25 of 40 ankles and lymphoid cell infiltration in 25 and pannus formation in 23, the rates of which were significantly higher than those of control and rats immunized with LPS for 15 and 29 weeks. The induction rate of arthritis in rats immunized with LPS was the same as that in rats immunized with E. coli. LPS and IL-1 were located in synovial cells and pannus in arthritic joints. Changes of RFLS level in rats immunized with LPS were elevated more gradually than those in rats immunized with E. coli. These findings suggest that LPS could stimulate IL-1 and RFLS production and may induce arthritis in rats resembling rheumatoid arthritis.


[Fresh allograft of intact growth plate into immature articular cartilage defects in rats].

In three inbred rat strains with a distinct major histocompatibility complex (MHC), MHC-matched allografts (Fisher, RT1l to Lewis, RT1l, n = 39) or MHC-mismatched allografts (Brown Norway, RT1n to Lewis, RT1l, n = 38) of fresh intact cartilage obtained from the tibial epiphyseal growth-plate were grafted into the defects in the femoral articular surface of immature rats. In the controls (n = 72), similar defect on the joint cartilage were made with no epiphyseal plate grafts. The present histological observation was continued throughout one year after transplantation. Total success rate of the repair was significantly better in MHC-matched allografts (92%) than in MHC-mismatched allografts (61%, p less than 0.001) or controls (19%, p less than 0.001). The MHC-matched allografts showed no signs of tissue rejection. However, the MHC-mismatched allografts showed evidence of lymphocyte infiltration and 13 (81%) of 16 grafts were rejected from 12 to 48 weeks after operation. These findings indicate that MHC-matched allografts of intact growth-plate have a potential to repair defects in immature articular cartilage over a long period of time, but MHC-mismatched allografts will eventually be rejected.


Three-dimensional organization of the cartilage canal--a scanning electron-microscopic study by vascular cast of the rabbit's femoral head.

The microvasculature of the cartilage canal was studied by plastic corrosion casting using a scanning electron microscopic (S.E.M.) method. At the 25th fetal day, the vascular architecture of the cartilage canal showed an unbranched channel terminated by dividing into a capillary glomerulus. In the later embryonic stage, the canals dilated throughout their course. At birth, before the appearance of the secondary center of ossification, the chondroepiphysis was well vascularized. Anastomosis between the epiphysis and the metaphysis preceded the occurrence of ossification. During the growth stage, the ossifying center was enlarging, the canals extended to the metaphyseal side more frequently than to the articular side. The communicating canals which had traversed the physis faded gradually. In the adult stage, the ossification center had developed completely. The cartilage canals on the surface of the ossification center disappeared. These results show that the cartilage canal has a significant role in the nutrition of the epiphysis and in the osteogenesis of secondary centers of ossification.


Effects of some natural products on sugar cataract studied with nuclear magnetic resonance spectroscopy.

Four commercial anticataract drugs and five flavonoids isolated from Chinese herbs were studied on their effects to inhibit sugar cataract formation in vitro using 13C-nuclear magnetic resonance spectroscopy (MRS). Pa-Wei-Di-Huan-Wan (PWDHW) and Zhang-Yan-Ming (ZYM) were effective in inhibiting sorbitol formation, whereas Bai-Nei-Ting (BNT) and Pearl Min-Mu-Ye (Pearl MMY) were ineffective in inhibiting sorbitol formation. Among five flavonoids tested, four were moderately effective in inhibiting sorbitol formation, and one was totally ineffective up to 1 x 10(-4)M used.


Vascular effects of acetylcholinesterase inhibitors in the rabbit eye: a study with fasciculin and physostigmine.

The vascular effects of fasciculin and physostigmine, two acetylcholinesterase inhibitors, were studied with radioactively labelled microspheres in the rabbit eye. In addition, the effects on the intraocular pressure, pupil size and the aqueous humor protein concentration were determined. Both drugs were injected intracamerally in pentobarbital anesthetized and indomethacin pretreated animals. Fasciculin injected in a dose of 0.5 micrograms (0.7 x 10(-10)M) reduced blood flow in the anterior uvea as determined 30 and 60 min after injection. Higher doses had inconsistent effects. Physostigmine injected in a dose of 3 micrograms (1.1 x 10(-8)M) also reduced blood flow in the anterior uvea. The effect was most pronounced in the iris. Neither drug had any appreciable effect on choroidal or retinal blood flow. Both drugs caused pupillary constriction but the reduction in blood flow was not secondary to miosis. The effects on the intraocular pressure and aqueous humor protein concentration were inconsistent. The reduction in blood flow of the anterior uvea after intracameral injection of acetylcholinesterase inhibitors is consistent with a cholinergic vasoconstriction previously described in the eye during electrical stimulation of the oculomotor nerve.


An in vitro comparison of the permeability of prednisolone, prednisolone sodium phosphate, and prednisolone acetate across the NZW rabbit cornea.

Controversy and ambiguity in the literature concerning the corneal penetration of prednisolone acetate over Prednisolone Sodium phosphate in NZW rabbits has recently prompted comparative studies using specific chromatographic assays. In vitro, corneal penetration studies were performed using the Ussing Chambers to compare the permeability and flux of both esters and prednisolone at 0.5% using a reversed phase HPLC-UV assay. Chromatograms of samples from the receiver chambers show primarily the presence of prednisolone from both esters; only prednisolone phosphate penetrated the cornea intact. Flux measurements were similar for prednisolone and both salt forms in terms of the metabolite prednisolone. Permeability coefficient calculations give the relative comparison: prednisolone acetate greater than prednisolone greater than prednisolone sodium phosphate.


Precorneal sampling techniques for ophthalmic gels.

Drug-cornea contact time is a critical issue in ocular drug delivery. Existing methods for its experimental determination are developed mainly for eye drops and ointments, and have not been reported for ophthalmic gels. The present study evaluated two tear film sampling techniques (capillary tubes and Schirmer strips) and one recovery technique (cotton swab) for their suitability for the determination of precorneal drug concentration as a function of time for ophthalmic gels. The study was conducted using the rabbit eye model, and the gel studied was a commercial polyacrylate-based gel containing pilocarpine HCl. The three techniques explored yield similar results with respect to drug-cornea contact time, about one hour for the gel studied. The strip method suffers from a gel-carry-over problem at the early time points; therefore it is not recommended for tear sampling until most of the gel is cleared from the cul-de-sac. Successful tear sampling was accomplished using capillary tubes. Drug concentration in the tear film as a function of time determined using this technique reveals not only the duration of contact between the drug and the cornea, but also demonstrates a nonuniform drug distribution in the tear film at the early time points (10 and 30 minutes). Finally the cotton swab technique is gentle, easy, and nondestructive. It recovers total drug remaining in the cul-de-sac but does not yield information for the tear film.


Absorption, distribution, metabolism, and excretion of bacteria-derived hyaluronic acid in rats and rabbits.

The feasibility of using bacteria-derived hyaluronate solution as a viscous aid for anterior chamber surgery was examined by studying the pharmacokinetic behavior and metabolic fate of 14C-labelled material, following administration to rats and rabbits. Intravenously-administered HA disappeared rapidly from the blood of rabbits and rats with a mean t1/2 of 5.3 and 3.7 min, respectively. The labelled material has concomittantly accumulated in the liver, where it was digested to oligomeric sugar subunits; these were further utilized metabolically either for energy generation or for incorporation into new high molecular weight species. Metabolic cage studies has indicated that most of the 14C-HA label administered intravenously to rats was excreted as CO2 via the respiration within 24h, while a smaller portion was excreted in the urine. The disposition of viscous 14C-HA administered into the anterior eye chamber of rabbits was slow and followed first-order kinetics with a t1/2 of 10.5h. No degradation occurred in the aqueous humour. Low blood levels of 14C-labeled material were found during 72h after intra-ocular administration. The results indicate that the absorption, distribution, metabolism and excretion of bacteria-derived HA is similar to those of the currently used ophthalmic surgery HA aids extracted from rooster combs.


Duration and long-term efficacy of phenylephrine-induced reduction in the systemic absorption of ophthalmic timolol in rabbits.

Co-administration of phenylephrine decreases systemic timolol absorption after a single topical ocular dose of timolol in rabbits. This is probably due to vasoconstriction in the conjunctiva of the eye and nasal mucosa. In this study, we evaluated the duration of action and long-term efficacy of phenylephrine in reducing the systemic absorption of ophthalmic timolol in pigmented rabbits. Although co-administered phenylephrine had a short duration of interaction with systemic timolol absorption (20-60 min), its effect on systemic timolol absorption was substantial. The long-term vasoconstrictive effect of phenylephrine was studied by administering timolol-phenylephrine eyedrops into the eyes of rabbits once a day for two months. Systemic peak concentrations of timolol following timolol-phenylephrine eyedrop administration remained unchanged throughout the study. Phenylephrine may be useful additive in decreasing the systemic concentrations of ophthalmic drugs.


LSU Medical Center initiates family medicine clerkship program for third year medical students.

This article takes note of the family physician shortage in Louisiana and the continuing need to inform medical students of the career choice in family medicine. Drs English, Gatipon, and Catlin describe the planning stages, the training of clinical teachers, and the implementation of a third (junior) year required clerkship in family medicine at LSU School of Medicine in New Orleans. The students who participated in the pilot year of the program have been enthusiastic about the value of the experience in their total medical education.


Nontyphi Salmonella sepsis in an eight-year-old boy.

Nontyphi bacteremia is a rare event in older children, especially in those without predisposing conditions. We report a case occurring in a normal 8-year-old boy from south Louisiana whose prolonged illness may, in part, have been iatrogenic. Antibiotic treatment is also discussed.


Cervical lymph node biopsy.

Controversy among head and neck oncologists has centered for many years around the appropriate and inappropriate use of cervical lymph node biopsy. Many authors contend that untimely cervical node biopsy, at best, is unnecessary, and, at worst, may lead to early recurrence and death. More recent data show that adjuvant radiation therapy may ameliorate the adverse effects of lymph node biopsy. At present, although cervical lymph node biopsy is not recommended for the diagnosis of head and neck cancer, it does not appear to shorten survival if appropriate management is administered subsequently.


Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice.

Sites of cutaneous infection with Leishmania major in genetically susceptible (BALB/c) and resistant (C57B1/6) mice were investigated for the early inflammatory response (6 h to 12 days) by electron microscopy combined with enzyme-histochemical methods. Susceptible BALB/c mice spontaneously recruited only polymorphonuclear leukocytes (PMNs) at the site of infection. Infiltrating mononuclear phagocytes (and eosinophils) were first observed at day 1 in a ratio equal to the influx of PMNs (about 40%). This pattern persisted during the following 11 days of infection. In the resistant C57/B16 mice, the first cellular infiltrate at the infected site contained mononuclear phagocytes (25%) and eosinophils (15%) besides PMNs (60%). Within 3 days after infection, mononuclear phagocytes became the dominant population of cells in cutaneous lesions (up to 80%). It was found in situ that L. major accumulated and replicated in immature macrophages, that is, intermediate stages between monocytes and resident macrophages, which were found in lesions of both strains. The burden of parasites was, however, degraded more rapidly by the infiltrating cells of the resistant mice than by those of the susceptible ones. Within the first 4 days of infection, the parasites were found in PMNs, mononuclear phagocytes, and extracellular spaces in both strains. In susceptible mice this distribution pattern persisted up to 12 days after infection; in resistant C57B1/6 mice parasites accumulated inside mononuclear phagocytes within this period. It is concluded that the features of acute inflammation during leishmaniasis in BALB/c mice are sustained over a prolonged period that is ineffective in the elimination of L. major.


Assessment of neutrophil leukocyte secretory response to fMLP in whole blood in vitro.

A simple, precise method has been developed for assessing neutrophil secretory responses (release of vitamin B12 binding protein from specific granules) to challenge of aliquots of whole blood with the bacterial chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Dose-response studies performed on blood from normal healthy volunteers showed higher maximal secretory responses in males than females (33.3 +/- SEM 2.2 vs. 27.4 +/- 2.5, P less than .005) a left shift in dose-response curves after feeding compared to fasting (P less than .005), spontaneous up-regulation of responses in blood incubated at 37 degrees C for 1 h, and marked upregulation in response to preincubation with endotoxin. This whole blood challenge method may be used to study neutrophil responses in groups of individuals or patients without the confounding effects of changes in cell responses resulting from cell isolation procedures. The method may also be used as a bioassay for neutrophil-activating factors.


Effects of phenobarbital on leukocyte activation: membrane potential, actin polymerization, chemotaxis, respiratory burst, cytokine production, and lymphocyte proliferation.

Leukocyte activation is known to involve cell membrane potential changes. Phenobarbital, an anesthetic and anticonvulsant that can inhibit neuronal membrane depolarization, may also affect leukocyte activation. Measuring membrane potential, actin polymerization, chemotaxis, superoxide production, lymphocyte proliferation, intracellular calcium concentration, and cytokine production, we found that phenobarbital at a concentration of 15-30 micrograms/ml, which is considered a therapeutic serum level for controlling seizures, did not affect polymorphonuclear neutrophil (PMN) activation. At levels higher than 100 micrograms/ml, phenobarbital significantly suppressed formylmethionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis. Concentrations greater than 300 micrograms/ml also inhibited phorbol myristate acetate-stimulated membrane potential change. In contrast, 30 micrograms/ml phenobarbital significantly inhibited lymphocyte proliferation stimulated by phytohemagglutinin (PHA) and pokeweed mitogen. This concentration of phenobarbital also suppressed the increase of intracellular free calcium induced by PHA. However, only a higher concentration of phenobarbital (300 micrograms/ml) was able to inhibit PHA-induced interleukin-2 (IL-2) production and suppress the proliferation of PHA-induced IL-2 receptor-bearing lymphocytes. These results suggest that concentrations of phenobarbital associated with anticonvulsive levels do not affect PMN activation but suppress lymphocyte activation, possibly by affecting intracellular signal transduction.


Impaired stimulus-response coupling in association with increased growth rate of HL60 cells.

Impairments in the respiratory burst and stimulus-response coupling were studied with respect to the increased rate of cell replication that occurred in HL60 cells during repetitive passages in cell culture. During a 45-week period of culture, HL60 cells developed a progressive increase in rate of replication. Concomitantly, undifferentiated cells developed an impairment in ATP-induced calcium mobilization. The percentage of cells that could be differentiated with dimethyl sulfoxide progressively diminished. Differentiated cells developed an impairment in both the respiratory burst and secretion of beta-glucuronidase. In addition, regulation of the respiratory burst by cAMP agonists including isoproterenol, adenosine, and prostaglandin E2 was reduced in rapidly proliferating cells. Thus, multiple changes in stimulus-response coupling occur during cell culture in association with an increase in rate of cell replication. It may be important to recognize progressive impairments in cell function in studies using repetitive samples of HL60 cells from a continuously maintained cell population. The observed impairments in stimulus-response coupling may be relevant to unregulated cell growth in neoplastic disease.


Effect of lipopolysaccharide on transport and metabolism of arginine in mouse peritoneal macrophages.

The transport activity of arginine in mouse peritoneal macrophages was strongly induced when they were cultured with 1 ng/ml bacterial lipopolysaccharide (LPS) for 12 h. Arginine in the medium decreased whereas ornithine in the medium increased during the culture. This time-dependent change of arginine to ornithine was accelerated by LPS. However, the activity of arginase in the macrophages did not change during the culture with or without LPS and release of arginase from the cells to the medium was not detected. It is suggested that the transport of arginine and ornithine was a rate-limiting step in arginine-to-ornithine conversion in the macrophage culture medium. A possible role of the induction of arginine transport activity in the macrophage cytocidal activity due to arginine depletion and nitric oxide production is discussed.


Type I interferons (IFN-alpha and -beta) suppress cytotoxin (tumor necrosis factor-alpha and lymphotoxin) production by mitogen-stimulated human peripheral blood mononuclear cell.

We studied the effect of the different types of interferons on the production of cytotoxin by human peripheral blood mononuclear cells (PBMCs) stimulated with the mitogen phytohemagglutinin (PHA). Maximum secreted levels of cytotoxin were observed at day 3 in culture and consisted of both tumor necrosis factor alpha (TNF-alpha) and lymphotoxin as determined by specific antibodies. Type I interferons (IFN-alpha and IFN-beta) consistently suppressed cytotoxin production. Both TNF-alpha and lymphotoxin were significantly suppressed. Mean suppression by IFN-alpha and IFN-beta (1000 U/ml) was 56 and 66%, respectively, in PBMCs from 18 different donors. The suppressive effects of IFN-alpha and IFN-beta on cytotoxin production were dose responsive over a range of 10 to 1000 U/ml. Type II interferon (IFN-gamma) did not have consistent significant effects. Pretreatment with IFN-alpha or IFN-beta for 24 or 48 h prior to PHA stimulation also resulted in significant suppression. Supplementation with interleukin-2 (10 U/ml) or IFN-gamma (1000 U/ml) did not overcome cytotoxin suppression by IFN-alpha or IFN-beta. Cytotoxin suppression by IFN-alpha and IFN-beta together appeared to be noninteractive. Suppression appeared not to be due to blockade of the cytotoxin release, since both cell-associated cytotoxin and secreted cytotoxin were suppressed to the same level. These results demonstrated that cytotoxin and lymphotoxin production by PHA-stimulated PBMCs could be down-regulated by type I interferons and that there is a substantial difference between the action of type I interferons and type II interferons (IFN-gamma) in modulating the biosynthesis of cytotoxins.


Effects of glucocorticoids on the TPA-induced monocytic differentiation.

The human monocytic cell line U937 was used as a model system to investigate the effects of glucocorticoids on monocytic differentiation. Upon incubation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 x 10(-9) M) for 48 to 72 h, the immature U937 cells ceased to proliferate and became morphologically and functionally macrophage-like. Preincubation of the cells with glucocorticoids (dexamethasone and prednisolone, 10(-7) and 10(-6) M) but not progesterone (10(-6) M) had marked effects: The cells remained in suspension and developed very little cell-cell interaction. This correlated with decreased expression of the surface molecules ICAM-1 and CD18 as determined by fluorescence-activated cell sorter analysis. The TPA-induced ability of the cells to release lysozyme or to generate reactive oxygen radicals (determined as reduction of nitroblue tetrazolium) was markedly reduced. The induction of cyclooxygenase activity and thus the ability to release prostanoids was almost completely abolished. Inhibition of prostanoid synthesis was also observed when the glucocorticoids were administered 24 or 48 h after TPA. The primary step of TPA induction, the activation and translocation of protein kinase C, however, was not affected by glucocorticoids as determined by activity measurements and Western blot analysis. There was no change in the subsequent TPA-induced induction of c-fos. The down-regulation of the differentiation-related oncogenes c-myc and c-myb was the same in cells treated with TPA in the presence or absence of glucocorticoids. Furthermore, no significant effect of glucocorticoids on the TPA-induced growth arrest was observed. Glucocorticoids thus interfere with TPA-induced functions, which are typical for activated macrophages; however, they do not impair the differentiation process and concomitant growth inhibition.


The myeloid leukemia cell line HL-60 produces a factor that induces chloride secretion in cultured epithelial cells.

When activated, polymorphonuclear leukocytes (PMNs) produce a small soluble factor, termed neutrophil-derived secretagogue (NDS), that elicits electrogenic Cl- secretion--the transport event responsible for hydration of mucosal surfaces. Work toward purification of this factor has been hampered by variability in activity of PMN-derived NDS. Using a human-derived intestinal epithelial cell line (T84) that serves as a model for studies of the regulation of electrogenic Cl- secretion, we find that the human promyelocytic leukemia cell line HL-60 secrets a factor with NDS-like activity. Buffer conditioned by HL-60 cells (10(7) cells/ml for 1 h), when applied to T84 monolayers grown on permeable supports and analyzed by routine electrophysiological techniques, elicited a short-circuit current (Isc) of 11.7 +/- 1.02 microA/cm2. This short-circuit current was sensitive to bumetanide, an inhibitor of the basolateral Na-K-2Cl cotransporter, and was dependent on the presence of chloride in the assay buffers. Such data indicate that buffer conditioned by HL-60 cells stimulates electrogenic Cl- secretion. Like NDS, the active factor in HL-60-conditioned buffer has a nominal molecular weight of less than 500 and was increased by activation of cells with phorbol ester. 125I and 86Rb efflux assays confirmed that the secretagogue released by stimulated HL-60 cells, similar to PMN-derived NDS, preferentially stimulates opening of Cl- rather than K+ channels in T84 cells. Lastly, release of NDS-like bioactivity increases when HL-60 cells are differentiated toward granulocytes compared to cells differentiated toward monocytes.


Fucose-activated killer cells. I. Enhanced TNF-alpha mRNA accumulation and protein production.

Our previous studies have shown that the monosaccharide alpha-L-fucose significantly enhances the cytolytic capacity of peripheral blood mononuclear leukocytes (PBMLs). To examine possible mechanisms through which fucose affects cytolytic activity, we studied the production of cytokines after alpha-L-fucose stimulation. In this report, we show that fucose induced a minor but significant augmentation of production of interleukin-2 (IL-2), but anti-IL-2 antibodies did not completely inhibit fucose-activated cytolysis. Fucose induced significantly higher secretion of TNF-alpha by both lymphocytes and monocytes. The nature of the lytic molecule detected in the TNF bioassay was verified with specific neutralizing antibodies. In addition, fucose induced the accumulation of TNF-alpha mRNA in a time-dependent manner with a peak at 8 h and a return to baseline values at 20 h after stimulation. In vitro nuclear transcription assays determined that fucose augmented the rate of transcription of the TNF-alpha gene, and inhibition of de novo transcription with actinomycin D indicated that the turnover rate of the TNF-alpha mRNA was not affected by fucose stimulation. We also determined that fucose did not modulate the mRNA expression of the pore-forming protein, a major lytic protein involved in lymphocyte cytotoxicity. Specific neutralizing antibodies indicated that TNF-alpha was not an effector molecule in fucose-activated killing of K562 or Raji target cells but that this cytokine had an essential role in the induction of the augmented killing by alpha-L-fucose.


Interleukin-6 in mouse hypersensitivity pneumonitis: changes in lung free cells following depletion of endogenous IL-6 or direct administration of IL-6.

In this study, we examined the role of interleukin-6 (IL-6) in the development of chronic lung inflammatory conditions, using a mouse model of hypersensitivity pneumonitis established by intranasal instillation of the thermophilic actinomycete Faeni rectivirgula. Challenged mice developed an early neutrophilic response at 24 h, followed by a macrophage/lymphocyte recruitment. The impact of IL-6 on the development of the inflammatory response was assessed by giving infusions of a monoclonal antibody against IL-6 so as to deplete endogenous levels of this cytokine or by giving exogenous IL-6 to challenged mice. Mice challenged intranasally with the actinomycete and given the anti-IL-6 antibody developed a strong, sustained neutrophilic response, with a significantly higher lung free cell number than control mice. Assessment of fibrosis by measuring lung hydroxyproline levels showed that challenged mice given anti-IL-6 developed more significant fibrosis than control mice. Conversely, infusions with IL-6 diminished F. rectivirgula-induced cell recruitments and the fibrotic response in the lungs. Moreover, alveolar macrophages from mice given 2 weeks of F. rectivirgula treatment released high levels of tumor necrosis factor alpha (TNF-alpha) bioactivity upon in vitro lipopolysaccharide challenge, compared to mice instilled with saline only. This TNF-alpha activity produced by macrophages was decreased by in vivo IL-6 treatment and enhanced by in vivo neutralization with anti-IL-6. These observations suggest that IL-6 may play a role in regulating the cellular recruitment in the lungs during an inflammatory response, with dramatic consequences for the cellular profile in the bronchoalveolar lavage and the subsequent fibrosis.


Effects of antiorthostatic suspension and corticosterone on macrophage and spleen cell function.

The purpose of this study was to determine whether antiorthostatic suspension of C3HeB/FeJ mice for a period of 11 days affected macrophage and spleen cell function. We found that antiorthostatic suspension did not alter macrophage secretion of prostaglandin E2, tumor necrosis factor alpha, and interleukin-1. Antiorthostatic suspension also did not affect macrophage-mediated contact-dependent cytotoxicity, TNF-mediated cytotoxicity, expression of class II histocompatibility molecules, or concanavalin A and Bandeiraea simplicifolia lectin binding sites. The proliferative response of splenic T cells in response to mitogens and staphylococcal exotoxins was significantly enhanced in antiorthostatically suspended mice. We detected significantly higher concentrations of corticosterone in the plasma of antiorthostatically suspended mice. Therefore, there did not appear to be any direct immunosuppressive effects of corticosterone on the parameters tested.


Tumor antigen presentation by epidermal antigen-presenting cells in the mouse: modulation by granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and ultraviolet radiation.

I-A+ epidermal antigen-presenting cells (APCs, Langerhans cells) have been shown to present tumor-associated antigens (TAAs) and to induce tumor immunity in vivo. This study examined the effects of ultraviolet radiation (UVR) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha) on the ability of epidermal cells (ECs) to induce or to elicit immunity against the murine spindle cell tumor S1509a. Naive syngeneic mice were immunized three times at weekly intervals with ECs that had been cultured in GM-CSF for 18 h and then pulsed with TAA derived from S1509a. This resulted in protective immunity against subsequent tumor challenge, providing a model to study the conditions required for sensitization against TAAs by epidermal APCs. Culture of ECs in GM-CSF was required for induction of significant protective tumor immunity, and UV irradiation or incubation in TNF-alpha for 2 h after GM-CSF incubation abrogated the immunostimulatory effect of GM-CSF. However, unlike UVR, TNF-alpha did not significantly inhibit the induction of immunity when ECs were exposed to TNF-alpha before overnight incubation in GM-CSF, together with GM-CSF, or after pulsing with TAA, and anti-TNF-alpha antibody treatment did not abrogate the effects of UVR on this system. Furthermore, TNF-alpha incubation of ECs augmented their ability to elicit delayed-type hypersensitivity (DTH) and also enhanced elicitation of DTH by GM-CSF-cultured ECs, whereas UV-irradiation reduced it in a dose-dependent fashion. Taken together, these results demonstrate that GM-CSF, TNF-alpha, and UVR are significant regulators of tumor antigen presentation by epidermal APCs and that the effects of the cytokines examined differ with regard to induction or elicitation of immunity.


Lytic effects of Actinobacillus actinomycetemcomitans leukotoxin on human neutrophil cytoplasts.

Actinobacillus actinomycetemcomitans leukotoxin lysed human neutrophil cytoplasts. The reaction was associated with a rapid influx of extracellular calcium, a collapse in membrane potential, release of lactate dehydrogenase, and overt disintegration of the plasma membrane. These functional and structural alterations in the plasmalemma of neutrophil cytoplasts reinforce the hypothesis that A. actinomycetemcomitans leukotoxin acts as a pore-forming, membranolytic agent and indicate that neutrophil cytoplasts are useful tools in studying the biology of membrane-active toxins.


Interactions between HIV-infected monocytes and the extracellular matrix: HIV-infected monocytes secrete neutral metalloproteases that degrade basement membrane protein matrices.

The frequency of human immunodeficiency virus (HIV)-infected monocytes that spread on a model basement membrane was about twofold greater than that of an equal number of uninfected control cells through the initial 12 to 18 h of culture. By 24 h, virtually all HIV-infected and uninfected control cells spread on the basement membrane gel. The frequency of spread cells in the uninfected control population was less than 10% of total cells by 12 days. In contrast, 30 to 40% of HIV-infected monocytes remained spread through this time interval and formed a dense interdigitated network of cell processes on and into the gel matrix. Invasion of the basement membrane matrix by HIV-infected monocytes suggested increased secretion of proteases able to digest the gel. Indeed, levels of neutral protease activity in culture fluids from HIV-infected monocytes were significantly higher than those from equal numbers of uninfected control cells. High levels of protease activity in culture fluids of HIV-infected monocytes required productive virus infection and were not observed with cells exposed to T cell-tropic HIV isolates. The predominant protease activity in these cultures was a 92-kd neutral metallogelatinase. HIV-induced changes in monocyte metalloprotease activity may be important for extravasation of infected cells to tissue or for the development of AIDS-associated neuropathology, carcinogenesis, and opportunistic infection.


The sexual difficulties of women.

Despite the fact that women are susceptible to experiencing a wide variety of sexual difficulties and complaints during their lifetime, it is also true that women are sexually resilient and are capable of satisfactory sexual response throughout their life cycle. Often, permission and reassurance, coupled with sensible suggestions are sufficient to overcome bothersome sexual difficulties. When this is not helpful, referral to a well-trained sexual or couples' therapist is indicated.


Hormones, behavior, and sexuality in women.

Many hormones are involved in the control of human sexuality. Clearly both androgens and estrogens are important parts of the picture. The physiologic role of prolactin, thyroid hormones and gonadotropins is not clear. The part played by neurotransmitters can only be guessed at. The neuroendocrine interaction governing female sexuality is far less understood than in the male. For example while there is a loss of tumescence in the vaginal tissue in diabetic females there is no loss of sexual function as in the male. The effects of deletion and addition of sex steroids in the female are far less predictable than in the male. Environmental and psychosocial factors are probably more important in the total picture. The role of hormones in the sexual function and psychological makeup of women is important. The exact role of the endocrine system in their psychosexual function is by no means clear. A great deal of research is required to ratify or disprove many of the speculative assertions found in today's literature. Studies of female sexuality would seem to have acquired a new urgency. Too often attempts at such serious study is met with a snicker and little or no funding is forthcoming. Unfortunately we know more about the sexuality of most animal species than our own. We have to take the study of female sexuality far more seriously to solve these problems.


Clinical features of systemic lupus erythematosus in Thai males and females.

From 1976 through 1988, 726 patients with systemic lupus erythematosus (SLE) were admitted to the Medical Service of Chulalongkorn Hospital, 666 cases (91.7%) being female and 60 cases (8.3%) male (the female-to-male ratio = 11:1). Clinical comparison of 60 males and 130 females (by randomized selection from the total of 666 females) was made. Onset of disease in males occurred later than in females (29.2 +/- 12.2 years vs 25.8 +/- 10.7 years, p less than 0.01). The majority of clinical manifestations were similar; however, musculoskeletal (63.3 vs 73.3%), cardiac manifestations (13.3 vs 26.1%) and Raynaud's phenomenon (18.3 vs 35.4%) were less common in males than females (p less than 0.01), whereas hematologic manifestations were more common in males than females (p less than 0.01).


Wilson's disease.

Fourteen cases of Wilson's disease in Thais were studied retrospectively. Most were in the second and third decades. The hepatic form occurs in all age groups and the most common presentation was cirrhosis and complications. Neurological complications were observed during the second decade and consisted of Parkinsonism, dystonic and pseudosclerotic forms. A Keyser-Fleisher ring was detected in 2/3 of the cases. D-penicillamine was the mainstay of our therapy. Death in this series was related to crisis such as acute hemolysis, hepatitis as well as septic complications of cirrhosis. Since Wilson's disease is a treatable and preventable disorder, early clinical diagnosis and screening of asymptomatic siblings is mandatory.


Double-blind evaluation of enalapril in patients with systolic heart failure.

Fifty-six patients with a mean age of 58 years, 14 females and 42 males, all with dominant systolic heart failure (33 in functional class 3 and 4) were randomised to receive either added placebo or added enalapril to their heart failure medication. There were 13 patients in this group who had their trial drug switched after a certain period to allow direct but blind comparison between placebo and enalapril. Cardiac mortality with enalapril was 32 per cent compared to 48 per cent with placebo at intervals after initiating therapy of 20.0 +/- 19.4 versus 14.3 +/- 11.5 months respectively. When compared to a preceding control period, 80 per cent of the enalapril patients improved in contrast to 21 per cent of the placebo. However, when a comparison was made directly between enalapril and placebo, enalapril was better in 31 per cent and placebo was better in 8 per cent of the patients. It is concluded that in certain patients with systolic heart failure from non-valvular and non-hypertensive causes, enalapril is beneficial when added to the conventional treatment. An argument is also presented that to cost-effectively identify the group who will benefit, a short term ACE-I trial after the conventional antifailure therapy can be considered in all patients with systolic heart failure.


Cholinesterase activity in the chondrocranium of normal and exencephalic mouse fetus with trisomy 12.

Cholinesterase (ChE) activity in the chondrocranium of normal and exencephalic trisomy 12 mouse fetuses was studied. Non-specific cholinesterase activity was found strongly in the developing bone cells at the central zone and weakly in the more maturely developed bone cells at the peripheral zone of the chondrocranium of both normal and exencephalic trisomy 12 mouse fetuses. In exencephalic mouse fetuses, the ChE-activity was lesser than in the normal ones which corresponded to hypoplastic chondrocranium. The centrifugal direction of the maturity of individual bone cells could be demonstrated by the activity of cholinesterase. The young bone cells showed strong ChE-activity while the more matured cells showed weak ChE-activity. The enzyme activity disappeared when the definite tissue structure was well developed. From this study, it may be concluded that ChE plays a role in chondrocranium development which is different from its known function in the adult tissue.


The correlation between osmolality and specific gravity of parenteral nutrition solution.

The correlation between osmolality and specific gravity of parenteral nutrition solutions containing various concentrations of amino acid and glucose were studied. There is good correlation between osmolality and specific gravity up to 1,000 mOsmol/kg H2O and 1.050, respectively. There are strong correlations between osmolality and amino acid concentration at each concentration of glucose. An equation which can be applied for quick calculation of osmolality of the solution from amino acid and glucose concentrations is: Osmolality (mOsmol/kg H2O) = 74.36 G + 163.91 A - 36.56. The results of this study can be adopted by all physicians for quick assessment of the osmolality of the PNS before administration to patients.


An investigation into the climacteric in Nigerians.

The alterations in the hormonal levels during menopause have been studied in Nigerian women. There was a significant decrease in estradiol level of early menopausal and late menopausal women while the testosterone level increased (P less than 0.01). The luteinizing hormone (LH) and follicle stimulating hormone (FSH) showed significant elevation (P less than 0.01). The elevation of follicle stimulating hormone was about fourteen times higher in early menopausal women and sixteen times higher in late menopausal women when compared to the level in controls. Luteinizing hormone, however, showed an elevation eight times higher in early menopausal women and twelve times higher in late menopausal women. The level of these hormones, the intensity of climacteric symptoms among menopausal Nigerian women and attainable age of menopause was found to be the same as in Caucasians.


Post-cesarean section puerperal morbidity. The incidence and risk factors at Srinagarind Hospital.

We found that the incidence of post-cesarean puerperal morbidity at Srinagarind Hospital, Khon Kaen University was 5.5 per cent, which is very low compared to other reports. Statistically significant risk factors for post-cesarean puerperal morbidity included having less than 4 antenatal care visits, duration of labour longer than 12 hours and absence of prophylactic antibiotics.


Febrile and infectious morbidity after abdominal hysterectomy at Srinagarind Hospital.

Two hundred and fifty-seven patients who had undergone total abdominal hysterectomy (TAH) in a rural University Hospital in Thailand between September, 1989 and May, 1990 were found to have an incidence of postoperative febrile and infectious morbidity of 35.4 per cent and 10.1 per cent respectively. The risk factors for febrile morbidity are administration of prophylactic antibiotics, a resident being the surgeon and duration of operation time of more than 120 minutes. The risk factors for infectious morbidity included history of previous surgery, performing TAH alone without adnexectomy and omentectomy and also operation time longer than 120 minutes.


Malignant histiocytosis: a chronic variant.

An 18-year-old woman had unusual clinical manifestations of malignant histiocytosis (MH) including a long duration of massive splenomegaly, absence of lymphadenopathy, and a number of exacerbations characterized by sudden onset of fever. During life, a definite diagnosis could not be established. The antemortem pathology of the marrow and liver was nonspecific and non-diagnostic. The diagnosis of MH was made after postmortem examination by histologic and immunohistochemical studies. The long duration of massive splenomegaly suggests that this patient could represent a chronic form of MH.


Upper urinary tract transitional cell carcinoma in patients with bladder carcinoma.

An upper urinary tract tumor following the initial diagnosis of bladder carcinoma is rare. We report 3 patients with bladder carcinoma who later developed upper urinary tract tumors. Ureteral tumor was diagnosed by ureterorenoscope in the first 2 patients, while in the third case, urothelial tumor involving the entire left upper tract was found at the time of planned operation for cystectomy. The etiology, risk factors, and investigation plans were reviewed, in order to make an early detection of tumors.


Primary tuberculosis of the nasopharynx.

A case of primary tuberculosis of the nasopharynx with cranial nerve 6 and 3 involvement is reported. The disease according to available statistics is very rare. The response to antituberculous therapy was very satisfactory.


Morphological estimation of total number of influenza A type virion spikes.

When purified and stored influenza A type virions were observed by the negative staining method in electron microscopy, we found disintegrated virions associated with a population of dispersed but clustered spikes. The total spike numbers of the clusters were morphologically counted, and their peak number (about 200) was consistent with the spike number measured by the molecular biology method, described in the other report.


An EDTA-KOH method to expose bone cells for scanning electron microscopy.

To observe bone cells by scanning electron microscopy (SEM), the mouse parietal bones were processed by decalcification with EDTA and digestion of collagen fibers with KOH to remove the bone matrix, in addition to the conventional preparation for SEM. The critical-point-dried specimens were split into two membranous pieces along the gaps formed by removing the bone matrix. By this method, osteoclasts showing full three-dimensional images of ruffled borders, osteoblasts showing special structures on the surfaces facing the bone matrix, and osteocytes extending many slender processes were clearly demonstrated in SEM. This new method may provide new viewpoints in bone cell biology.


The use of t-butyl alcohol in the microdissection of resin corrosion casts for SEM.

We developed a new method using t-butyl alcohol in the microdissection of microvascular resin casts of the rat cerebral cortex for scanning electron microscopy. Brains injected with Mercox resin were eroded with sodium hypochlorite solution and dehydrated with graded ethanol. The resin casts obtained were embedded and frozen in t-butyl alcohol at 4 degrees C, and shaved through the planes of interest parallel to the brain surface with a razor blade. The sections were directly freeze-dried and coated with gold and platinum for scanning electron microscopy. Our method enables the demonstration of cross sections of the fine microvascular networks by SEM without any contamination or mechanical artifacts such as distortion and destruction.


Quantitative and morphological observations on the ultrastructure of articular tissue generated from free periosteal grafts.

This study investigates the ultrastructure of articular tissue generated on osteochondral defects in skeletally immature rabbits from free reversed periosteal allografts after 50 and 100 days of post-operative intermittent active motion. Tissue samples prepared for transmission electron microscopy were compared with normal cartilage and periosteum in terms of cell morphology and the pattern of intercellular collagen deposition. Well-differentiated tissue demonstrated many ultrastructural features of normal articular cartilage while poorly differentiated samples contained cells and intercellular collagen profiles which were somewhat similar to those observed in periosteum.


Effects of phalloidin on the epithelial regeneration in the mouse gastric mucosa.

Effects of phalloidin on the early (5-60 min) processes of wound repair were examined in the ethanol-injured mouse gastric mucosa. Within 5 min after ethanol was washed out from the stomach, survived epithelial cells changed their shape and became flat extending both lamellipodia and filopodia. The denuded basal lamina was re-covered by these stretched cells within 30 min. When a low dose of phalloidin (5 micrograms) was applied to the wounded stomach, it took 60 min or more to cover the exposed basal lamina. Epithelial cells at the wound edge of the phalloidin-treated stomach often contained unusually thick layer of microfilaments in their subapical region. This observation suggests that phalloidin induces active microfilament assembly mainly in the apical region of epithelial cell processes.


Dexfenfluramine in the treatment of severe obesity: a placebo-controlled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behaviour.

Dexenfluramine, an effective and safe serotoninergic drug with anorectic and possible food-selection-tuning properties, was investigated in a placebo-controlled study of 1 year's duration in severe and refractory obesity. The aim of the study was to assess weight loss, and changes in cardiovascular risk factors, food intake and eating behaviour. Dexfenfluramine- and placebo-treated patients achieved a similar weight loss (greater than 10% of initial weight, by 39.5 and 30.0%, greater than 20% of initial overweight by 42.1% and 32.5% and greater than 10 kg by 41.4 and 33.3%, respectively, of the initial cohorts). Furthermore, the decreases in weight (10.7 vs. 8.0 kg), in body mass index (3.9 vs. 2.9 kg m2) and in waist/hip ratio (0.04 vs. 0.02) were not significantly different. After discontinuation of the drug, the increase in weight (2.8 vs. 1.0 kg) was significantly higher in the dexfenfluramine-treated group. Except for a borderline better effect on glucose of dexfenfluramine, both groups showed similar beneficial changes in food intake and cardiovascular risk factors. Eating behaviour in response to emotional and external stimuli was comparable in the two groups, but placebo-treated patients had to restrain their eating more in order to achieve the same weight loss. Notwithstanding the fact that weight losses and an associated amelioration of health-risk factors were of similar magnitude in dexfenfluramine- and placebo-treated patients, dexfenfluramine might have a useful role in promoting a less stressed adherence to prolonged restriction of energy intake in the severe and refractory obese subject.


Influence of a meat-free diet on the urinary excretion of 3-methylhistidine and creatinine in chronic renal failure.

Urinary excretion of 3-methylhistidine has been proposed as an index of internal protein breakdown provided that the intake of exogenous 3-methylhistidine (meat) is excluded. To evaluate the potential use of 3-methylhistidine in the metabolic assessment of patients with advanced renal failure, we studied a group of 11 patients with markedly reduced renal function who were put on a meat-free diet (the protein intake was kept constant). Steady-state plasma concentration and urinary excretion of 3-methylhistidine were not achieved until 14 d after exclusion of meat from the diet. At that time the plasma concentration and urinary excretion of 3-methylhistidine had decreased by 43% and 60%, respectively. We conclude that the delay in reaching steady state makes the clinical use of urinary excretion of 3-methylhistidine in patients with advanced renal failure unpracticable as an index of protein breakdown. The exclusion of meat also resulted in a continuous decrease in the plasma level and urinary excretion of creatinine, with the result that plasma creatinine or its reciprocal become misleading for evaluation of changes in renal function until a new steady state has been reached.


Drug-induced hepatic injury: an analysis of 1100 cases reported to the Danish Committee on Adverse Drug Reactions between 1978 and 1987.

The Danish Committee on Adverse Drug Reactions received 1100 reports of suspected drug-induced hepatic injury during the decade 1978-1987. The causal relationship between drug and hepatic injury was classified as definite in 57 (5.2%) reports, probable in 989 (89.9%) reports, possible in 50 (4.5%) reports and unclassifiable in four (0.4%) reports. Hepatic injuries accounted for 5.9% of all adverse drug reactions reported, and 14.7% of the lethal adverse drug reactions. A total of 47.2% were classified as acute cytotoxic, 16.2% as acute cholestatic and 26.9% as abnormal hepatic function. In 52 (4.7%) cases the hepatic injury was lethal; only 14 (1.3%) cases were chronic. Halothane accounted for 25% of the cases. The incidence of halothane-induced hepatic injury is decreasing, and only one lethal case has been reported since 1981. Next to halothane, sulfasalazine was the drug most often suspected during the last 2 years of the decade. Based on consumption data, the incidence of hepatic injury due to sulindac was estimated to be 18-fold higher than that due to ibuprofen. Paracetamol was reported to induce acute cytotoxic as well as cholestatic reactions in non-alcoholic subjects taking therapeutic doses.


Treatment of orthostatic hypotension with sleeping in the head-up tilt position, alone and in combination with fludrocortisone.

We studied the effect of sleeping in the head-up tilt (HUT) position, alone and in combination with fludrocortisone, on orthostatic tolerance and blood pressure (BP) in six patients with hypoadrenergic orthostatic hypotension. A high salt diet of 150-200 mmol Na+ d-1 was also administered. Combined treatment reduced orthostatic dizziness in all patients (P less than 0.001), and increased the maximal standing period to at least 10 min. HUT alone (n = 4) reduced the BP decrease after 1 min of standing from -64/-42/-25 +/- 29/21/17 mmHg to -53/-37/-23 +/- 31/24/20 mmHg (P less than 0.01 for systolic BP). Addition of fludrocortisone to HUT (HUT/fludro) (n = 5) further reduced the BP decrease after 1 min of standing from -63/-40/-24 +/- 20/12/11 mmHg to -21/-19/-8 +/- 12/10/5 mmHg (P less than 0.05 for systolic, mean and diastolic BP, respectively). BP at maximal standing time increased from 58/47/42 +/- 9/8/7 mmHg initially to 95/69/57 +/- 27/22/20 mmHg during combined treatment (P less than 0.05 for systolic and mean BP), and remained unchanged during the 14-month (range 8-70 month) follow-up period. Nocturnal sodium excretion decreased from 8.0 +/- 2.3 mmol h-1 to 5.9 +/- 1.9 mmol h-1 with combined treatment; body weight increased by 1.6 kg on average (range 0.5-2.4 kg) (P less than 0.01). We conclude that the combination of HUT and fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic BP in patients with hypo-adrenergic orthostatic hypotension.


Reproducibility of symptom-limited exercise-stress testing performed 2 and 6 weeks after myocardial infarction.

To assess the reproducibility of variables with prognostic value from exercise testing, two symptom-limited treadmill exercise tests were performed in 76 consecutive patients at 2 weeks (predischarge) and 6 weeks after myocardial infarction. In addition, cardiac catheterization was performed at 6 weeks. Exercise duration showed a moderate increase from 7.9 +/- 4.4 min to 8.8 +/- 3.0 min (NS). The rate-pressure product increased from 22,377 +/- 5491 to 24,832 +/- 7261 (P less than 0.001). Reproducibility of ST-segment depression was dependent on the initial response: among the group of 25 patients with ST-segment depression at 2 weeks, only 13 (52%) patients had a reproducible result, whereas among the group of 51 patients without initial ST-segment depression, 40 (78%) patients showed reproducibility. There was no difference in coronary anatomy or ejection fraction between the groups with and without reproducibility results. Among the 30 patients with initial ST-segment elevation, 15 (50%) patients showed reproducibility, while among the 46 patients without initial ST-segment elevation, 42 (91%) patients showed reproducibility: the ejection fraction was significantly higher in the latter group than in the group of patients with lower reproducibility. Thus predischarge exercise testing in postinfarction patients identifies a different group of patients at risk compared to exercise testing after 6 weeks, due to considerable variation between the two tests.


A prospective study of the incidence of deep-vein thrombosis within a defined urban population.

In a prospective study all positive phlebographies within the well-defined population of the city of Malmö, Sweden, during 1987 were studied in order to determine the incidence of deep venous thrombosis (DVT). Epidemiological data were analysed for the detection of patient groups at increased risk of DVT. The incidence was found to be equal for both sexes, i.e. 1.6 per 1000 inhabitants a year. Risk factors were found to be in accordance with earlier studies. The median age for men was 66 years, compared to 72 years for women. At diagnosis of DVT, 19% of subjects had a known malignancy and within 1 year 5% (19 cases) developed a new malignancy. Of the men, 29% had postoperative or post-traumatic (fracture) DVT, compared to 46% of the women. Fewer patients with DVT than expected (39%) belonged to blood group 0 (31%) (P less than 0.005). Pulmonary embolism (PE) was clinically suspected in only 5% of cases, and diagnosis was verified scintigraphically in 2% of cases. None of these died of PE, but of 6 patients who were found to have PE at autopsy, four died about 4 weeks after the DVT was diagnosed.


Normoalbuminuria ensures no reduction of renal function in type 1 (insulin-dependent) diabetic patients.

Recent reports have suggested that impaired renal function in type 1 diabetic patients may be present despite normal urinary albumin excretion (UAE). We have studied kidney function by means of a constant-infusion technique in normoalbuminuric type 1 diabetic patients without antihypertensive medication (UAE less than 20 micrograms min-1, n = 134), in microalbuminuric patients (20 greater than or equal to UAE less than 200 micrograms min-1, n = 50) and in 27 non-diabetic control subjects. Mean UAE was 4.5 micrograms min-1 (range 1.0-19.3 micrograms min-1) in normoalbuminuric patients, 53.1 micrograms min-1 (range 20.8-147.5 micrograms min-1) in microalbuminuric patients, and 4.0 micrograms min-1 (range 2.1-17.9 micrograms min-1) in controls. Glycosylated haemoglobin A1c was significantly higher in microalbuminuric patients (8.9%, range 5.9-12.6%) than in normoalbuminuric patients (7.9%, range 5.5-11.5%) (P less than 0.0001). Glomerular filtration rate in normoalbuminuric patients (135 ml min-1, range 97-198 ml min-1) was significantly higher than in controls (118 ml min-1, range 94-139 ml min-1) (P less than 1 x 10(-6), and significantly lower than in microalbuminuric patients (142 ml min-1, range 100-186 ml min-1) (P less than 0.05). Mean arterial blood pressure was lower in normoalbuminuric patients (91 mmHg, range 78-108 mmHg) than in microalbuminuric patients (98 mmHg, range 82-131 mmHg) (P less than 1 x 10(-6), but not significantly different from that of controls (89 mmHg, range 73-103 mmHg). We conclude that normal UAE is a reliable indicator of well-preserved renal function. Glomerular hyperfiltration, elevated blood pressure and poor metabolic control are characteristic features of microalbuminuric patients.


Syncope in young adults: evidence for a combined medical and psychiatric approach.

To determine the principal causes and effects of syncope in young adults, we prospectively evaluated 197 consecutive patients referred to a Syncope Specialty Clinic, comparing young (age 16-39 years, n = 71), middle-aged (age 40-65 years, n = 70) and elderly (greater than age 65 years, n = 56) patients. Psychiatric aetiologies were significantly more common in young patients (39% vs. 20% in middle-aged, and 3.6% in the elderly; P less than 0.001), while cardiac aetiologies were rare in the young (2.8% vs. 12% in the middle-aged, and 16% in the elderly; P less than 0.04). These differences were still significant after controlling for gender. Because psychiatric causes are so common in young patients, we evaluated hyperventilation as a bedside test for syncope patients and found it to have a positive predictive value of 59% for psychiatric causes of syncope. Syncope interfered with daily activities in 62% of young patients, and resulted in anxiety or depression in 70% of the young (no difference when compared with other age groups). Thus syncope in young adults can be a disabling medical condition requiring a unique medical and psychological approach to diagnosis and treatment.


Extrinsic allergic alveolitis due to exposure to esparto dust.

We here describe the case of a patient with a history of exposure to esparto grass for two and a half years, who presented with clinical symptoms, radiological signs, pulmonary function test and histological findings consistent with the diagnosis of hypersensitivity pneumonitis. Signs and symptoms reappeared after re-exposure. There are few reports of stipatosis in the world literature.


Fatal adult Henoch-Schönlein purpura due to small intestinal infarction.

A 57-year-old woman presented with classical symptoms of Henoch-Schönlein purpura including arthralgia, abdominal pain, palpable purpuric rash and abnormalities of the urinary sediments. The clinical course was subsequently complicated by severe paralytic ileus leading to respiratory embarrassment. Laparotomy confirmed patchy areas of small bowel infarction due to necrotizing vasculitis. Skin biopsy revealed extensive leukocytoclastic vasculitis with granular deposits of IgA in the blood vessels. Anti-neutrophil cytoplasmic autoantibodies (ANCA) were not detectable. The patient continued to deteriorate despite bowel resection, intensive immunosuppressive therapy and plasma exchange, and eventually died. Gastrointestinal involvement in adult Henoch-Schönlein purpura has previously been reported to have a favourable clinical course. However, our case illustrates the rate but lethal complication of intestinal infarction in patients who fail to respond to conservative treatment.


Autoimmune reactions in patients with M-component and peripheral neuropathy.

A study of 17 patients with autoimmune axonal or demyelinating peripheral neuropathy in combination with M-component is described. The M-component was associated with MGUS (monoclonal gammopathy of undetermined significance) in 12 patients, CLL in one patient, Waldenström's disease in one patient, and myeloma in three patients. Immunohistological examination with direct and indirect fluorescence showed binding of antibodies to nerve structures of the same class and light chain as seen in the M-component. In five cases of IgM M-component, the demyelinating neuropathy was caused by binding of the IgM M-protein and complement C3b to myelin-associated glycoproteins (MAG). In 12 cases with axonal neuropathy, binding of IgG to the connective tissue of the peri- and endoneurium was found in 50% of cases, IgM in five cases, and IgD in one case. None of the patients had central nervous system (CNS) symptoms. The clinical and therapeutic difficulties are discussed; only two patients with an acute course responded to immunosuppression. A marked co-expression of other autoimmune phenomena is interpreted in the light of cross-reactions between the autoantibody and similar tissue autoantigens.


Acute myelomonocytic leukaemia with infiltrative peripheral neuropathy.

The case of a 71-year-old woman with acute myelomonocytic leukaemia and severe pains in her arms, legs and back during treatment is described. Signs of a generalized polyneuropathy subsequently developed. Autopsy revealed massive leukaemic infiltration of peripheral nerves. Peripheral nerve involvement in acute leukaemia appears to be rare as judged from the very few previously reported cases. The condition should be suspected whenever inexplicable pain problems and signs of peripheral neuropathy occur in patients with acute leukaemia.


Neural and behavioral correlates of emotion recognition in children and adults.

Event-related potentials (ERPs), accuracy scores, and reaction times were used to examine the recognition of emotional expressions. Adults and 7-year-old children saw upright and inverted chromatic slides of the facial expressions of happiness, fear, surprise, and anger, and were asked to press a button for either "happy" or "angry" faces. A positive-going waveform (P300) was apparent at parietal scalp (Pz) and at left and right temporal scalp. Although the behavioral data were similar for both children and adults (e.g., both had more difficulty recognizing angry expressions than happy ones, and angry expressions were more difficult to recognize upside-down than were happy faces), the ERPs indicated that children responded differently than adults did to happy and angry expressions. Adults showed greater P300 amplitude to happy faces, while children showed greater P300 amplitude to angry faces. In addition, for adults, but not children, there were greater P300 amplitude responses at right vs. left temporal scalp.


The effect of object alignment on the representation of depth in young children's drawings.

Light and Humphreys (1981, Journal of Experimental Child Psychology, 31, 521-530) provided evidence that young children's drawings, despite infrequently showing view-specific occlusion, do systematically reflect spatial relations within an array. The present research tested the hypothesis that young children's preferences for canonical "best views" interact with array-faithful tendencies to increase early uses of occlusion. Forty-three children between 4 and 7 years of age drew arrays like Light and Humphreys' end-to-end alignments, with end-on views of objects in depth, and arrays aligned side-to-side, with canonical side-views of objects in depth. Significantly fewer single-object, view-specific occlusions were produced for end-to-end than for side-to-side alignments. Nevertheless, the former reveal that more children are able to use the vertical dimension to depict multiple objects in depth. Other comparisons suggest an interaction in multiple-object depictions of canonicality with spatial dimension and graphic complexity.


The perception of identity by 6 1/2-month-old infants.

In Study 1, sixteen 6 1/2-month-olds were habituated to a Reversible stimulus (an upright face that could be perceived as an entirely different upright face when it was rotated 180 degrees) and to a Nonreversible stimulus (a face that could be perceived as upright in only one orientation). Following habituation for each type of stimulus, test trials paired the habituated face with a novel stimulus (an inversion of the same face). For both Reversible and Nonreversible stimuli, the physical difference between the old and new test stimuli was the same (a 180 degrees rotation); however, infants devoted more visual attention to the 180 degrees rotation only when it was a Reversible face, suggesting that the identity change was detected. Experiment 2 ruled out the explanation that infants might have failed to dishabituate to the inversion of the Nonreversible stimulus because they could not remember it. Results are interpreted as evidence that 6 1/2-month-old infants are not limited to face recognition based on similarity in pattern arrangement alone, but are capable of processing faces at a representational level.


Asphyxial deaths from the recreational use of nitrous oxide.

The recreational use of nitrous oxide is widespread. Nitrous oxide for recreational use is usually obtained from anesthesia tanks or whipped-cream machine chargers or cans. Twenty previously described deaths associated with recreational nitrous-oxide use describe anesthesia tanks and whipped-cream machine dispensors as a source. Five deaths associated with nitrous oxide use are presented; two involving whipped-cream cannisters as the source, two involving anesthesia tanks, and one involving a racing fuel tank as a source of nitrous oxide. Autopsy findings in our cases were subtle or negative, but usually suggestive of asphyxia. Through a laboratory simulation, we have confirmed that nitrous oxide displaces oxygen in a closed space, which probably leads to asphyxia. A review of the literature, neuropharmacology, and pathophysiology of nitrous oxide use is also presented.


Electrocution: a review of 155 cases with emphasis on human factors.

A review of 155 cases of electrocution were investigated to determine the role of human factors, such as carelessness and intoxication, as contributions. The cases were retrieved by computer coding from the repository of the Armed Forces Institute of Pathology, covering the period 1955-1988. The cases are predominantly of military origin. Cases were divided into low-voltage electrocution (N = 47), high-voltage electrocution (N = 79), lightning strikes (N = 16), and unclassified (N = 13). For each group, data is presented on the circumstances of the incident and the pathologic findings. Blatant carelessness, misuse or improper maintenance of equipment, and intoxication are analyzed as contributory factors.


Fungal tunneling of hair from a buried body.

Tunnels produced in human head hair by fungal hyphae were examined with a light microscope and with a scanning electron microscope. The tunnels had small diameters and exhibited minimal branching. The use of a backscattered electron detector facilitated the locating of the openings of the tunnels in the surfaces of the hairs. In the backscattered electron image, tunnel openings appeared as dark spots. The tunneling hyphae did not show a preference for a particular location for entering the shaft of the hair. Some hyphae penetrated under the free edges of the cuticular scales, while others burrowed through the surfaces of the scales.


A microscopic comparison of fresh and burned bone.

Examination of the microstructure of human bone is useful in estimating age at death in forensic science cases. This technique has been tested and is well accepted, however samples of burned bone may complicate analysis because of possible changes in the microstructure occurring during the burning process. In a comparison of fresh and burned ground thin sections taken from midshaft femorae of eight dissecting-room cadavers of known age and sex, this study finds significant shrinkage of microstructural elements through the burning process. These results are compared to previous work on the subject, which found the microstructural elements to increase through the burning process.