The use of drugs in emergency airway management in pediatric trauma.

Most patients who require emergency airway control receive drugs to induce rapidly sufficient anesthesia for direct laryngoscopy and endotracheal intubation, but there are no protocols that outline the use of specific drugs in general use. Drugs should safely and rapidly produce (1) unconsciousness; (2) paralysis; and (3) blunt intracranial pressure (ICP) responses to airway procedures. Consequences to be considered include increased ICP, hemorrhagic shock, and a full stomach. To refine the use of drugs used for airway procedures in pediatric trauma patients, the authors reviewed all cases of emergency endotracheal intubation over a recent 12-month period (1) to see whether medications used met the goals of producing unconsciousness and paralysis and blunting ICP responses were met safely; and (2) to identify potential drug-related complications. From July 1, 1990, to June 30, 1991, 60 of 791 children (7.6%) required endotracheal intubation at the scene of injury, at the referring hospital, or in our emergency department (15; 25%). Ten patients died (16.7%). Three fourths were younger than 9 years of age. All except one suffered blunt injuries. Nearly all (95%) suffered head injuries, isolated in 39 of 57 (68.4%) and combined with injuries in other regions in 18 (31.6%). Fifteen patients were in apnea (25%); seven were both apneic and pulseless. Three fourths (45 of 60) had diminished levels of consciousness; one fourth (15 of 60) were awake. Immediate endotracheal intubation proceeded appropriately without drugs in all seven patients in cardiopulmonary arrest. Only eight of the remaining 53 patients (15.1%) received an optimal medication regimen. Many patients with head injury were inadequately protected against increases in ICP. Thiopental, an effective anesthetic agent that effectively lowers intracranial pressure, was not used in 25 of 35 stable patients with isolated head injury (71.4%). Intravenous lidocaine was not used in 38 of 50 head-injured patients in whom it would have been an appropriate adjunct to control increases in ICP (76%). Eight patients received paralyzing agents alone, without sedatives or narcotics. Medications were thought inadequate to relieve the pain and discomfort of laryngoscopy and endotracheal intubation in 32 of the 53 patients who should have received them (60.4%). No paralyzing agents were used in 36 of the 53 instances where it would have been appropriate (67.9%). In two of 11 instances (18.3%) where succinylcholine was administered, no prior nondepolarizing agent was used. Complications of a full stomach at the time of emergency endotracheal intubation became evident in 10 patients (16.7%) who vomited during procedures to control the airway. Two patients (3.3%) aspirated.(ABSTRACT TRUNCATED AT 400 WORDS)


Ganglioside GM2 levels in human melanoma cells: inverse correlation with lysosomal beta-hexosaminidase A activity.

GM2 is usually significantly elevated in human melanoma cells. The lysosomal hydrolase beta-hexosaminidase A (Hex A), is an isoenzyme required for terminal GalNAc hydrolysis from intact GM2 to GM3. The objective of the present studies is to determine if the elevated levels of gangliosides, particularly GM2, correlate with the activity of Hex A in cultured melanoma cells. The Hex A activity in 13 melanoma cell lines ranged from 26%-88.3% There was a inverse correlation between GM2 nmole/g and Hex A activity (r = -0.48; p less than 0.003). An inverse correlation (p less than 0.03) occurred between GD2 nmole/g and Hex A activity. There was an inverse correlation (r = -0.53; p less than 0.05 and r = -0.51; p less than 0.05, respectively) between the ratio of substrate/product (GM2/GM3) and (GD2/GD3) and Hex A activity. These results indicate that the level of GM2 in melanoma is inversely correlated with the level of activity of Hex A.


Fetal gastro-intestinal and abdominal wall defects: associated malformations and chromosomal abnormalities.

During an 8-year period (1983-1991), blood karyotyping was performed in 235 fetuses with abdominal wall or gastro-intestinal tract defects. The overall incidence of chromosomal abnormalities was 29% (trisomy 21, n = 12; trisomy 18, n = 44; trisomy 13, n = 7; deletion of the short arm of chromosome 5, n = 1; unbalanced translocation involving chromosomes 4 and 15, n = 1; triploidy, n = 1; Klinefelter's syndrome, n = 1; and Beckwith-Wiedemann syndrome with mosaic duplication 11p15, n = 1). The karyotype was abnormal in 42 (36%) of the 116 fetuses with exomphalos, in none of the 26 with gastroschisis, in 10 (43%) of the 23 with duodenal atresia, in 18 (75%) of the 24 with lack of visible stomach, in 1 (4%) of the 24 with dilated bowel and in 2 (7%) of the 27 with echogenic hepatic nodules or abdominal cysts. Abnormal karyotypes were more commonly encountered when there was ultrasonographic evidence of multiple malformations (43%) compared to isolated defects (2%). Survival in fetuses with exomphalos (33%), absent stomach (4%), and large bowel obstruction (13%) was poor, whereas in those with gastroschisis (73%) or abdominal cysts (88%) survival was high; in small bowel obstruction and in duodenal atresia, survival was 65 and 57%, respectively.


Fetal T-lymphocyte subpopulations in normal pregnancies.

Peripheral blood T lymphocyte subpopulations were measured, using a fluorescence-activated cell sorter, in fetal blood samples obtained either by cordocentesis (n = 118) or at elective caesarean section (n = 14). Both the numbers and percentages of the total T lymphocytes (CD3+) and T-helper lymphocytes (CD4+) increased exponentially with gestation from respective means of 46% (1.15 x 10(9)/l) and 29% (0.70 x 10(9)/l) at 16 weeks to a plateau of 75% (3.11 x 10(9)/l) and 54% (2.10 x 10(9)/l) at 34 weeks. Similarly, the number of suppressor/cytotoxic T lymphocytes (CD8+) increased linearly with gestation from a mean of 22% (0.55 x 10(9)/l) at 16 weeks to 24% (0.96 x 10(9)/l) at 40 weeks; there were no natural cytotoxic T lymphocytes (CD3+CD56+) in any of the fetal blood samples. The helper-to-suppressor T lymphocyte ratio (CD4/CD8) increased exponentially with gestation from a mean of 1.22 at 16 weeks to 2.57 at 28 weeks. The alterations in T lymphocyte subpopulations were accompanied by changes in the expression of CD45RA, L-selectin, CD25 and HLA-DR. These alterations in T lymphocyte subpopulations with gestation reflect the pattern of maturation and development of the fetal cell-mediated immune system.


Pathophysiology of polyhydramnios in twin transfusion syndrome.

In 3 cases of severe twin transfusion syndrome we demonstrate that the concentration of atrial natriuretic factor (ANF) in the cord blood of recipient twins is significantly elevated compared to that of donor twins. The discrepancy between recipient and donor concentration correlates with the volume of transfusion. The following pathophysiological mechanism for explaining polyhydramnios in recipient twins is proposed: chronic overload in recipient twins causes enhanced release of ANF from the fetal heart. Consequently, increased fetal urine production leads to polyhydramnios, which is additionally enhanced by inhibition of ADH release.


N-methyl-D-aspartate receptor antagonist MK-801 and spatial memory representation: working memory is impaired in an unfamiliar environment but not in a familiar environment.

Female Sprague-Dawley rats were injected with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 or saline 30 min before daily testing in spatial working memory (WM) and reference memory (RM) procedures in an 8-arm radial maze. MK-801 impaired RM and WM acquisition but not performance when rats were trained to criterion before drug administration. Neither a 2-hr nor a 4-hr delay between the first and last 2 correct WM choices impaired long-term WM. MK-801 impaired WM performance in trained rats only when rats were tested in a new environment. Thus, 2 mechanisms may be required for relational memory: an NMDA-dependent mechanism for acquiring long-term spatial representations and an NMDA-insensitive mechanism for operating on these stored representations.


MK-801 prevents brain lesions and delayed-nonmatching-to-sample deficits produced by pyrithiamine-induced encephalopathy in rats.

Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task and assigned by block randomization to one of four treatments: pyrithiamine-induced thiamine deficiency (PTD), PTD with administration of MK-801 after 12 days, control with MK-801 treatment, and control without MK-801. After 15 days of treatment followed by 21 days of recovery, the PTD rats showed significant deficits for DNMTS accuracy at retention intervals (RI) that ranged from 3.0 s to 15.0 s, the RIs that produced 75% accuracy on DNMTS in staircase training, and the rate at which a novel radial arm maze task was learned. The PTD-treated rats had consistent lesions in the thalamus and the mammillary bodies. MK-801 protected rats from both behavioral deficits and brain lesions (assessed quantitatively and qualitatively) that were produced by the PTD treatment.


Oncogenes, onco-suppressors, carcinogenesis and oral cancer.

The regulation of cell growth is fundamental to the maintenance of health: disturbed regulation can result in neoplasia. Genes in normal cells (protooncogenes) code for proteins involved in the regulation of cell growth and differentiation; abnormalities in these genes (oncogenes) or their expression are often involved in the development of cancer. This paper summarises the essentials of the complex cell growth regulatory mechanisms, their genetic control, and their disturbances in neoplasia, emphasising the role of cancer-promoting (oncogenes) and suppressing genes (onco-suppressors or anti-oncogenes), especially in relation to oral carcinoma, and discusses the possible role of viruses as one cause of neoplasia.


The role of secondary cytoreductive surgery in epithelial ovarian malignancies.

The benefit of aggressive primary cytoreductive surgery in the management of patients with advanced epithelial ovarian cancer has been confirmed. The value of secondary cytoreductive surgery, however, is less clear. This approach is being studied in four categories of patients: (1) those clinically free of disease after a planned regimen of first-line chemotherapy who are found to have macroscopic tumor at second-look laparotomy; (2) patients found to have bulky, unresectable tumor at initial surgery and who undergo interval cytoreduction as part of a planned chemosurgical treatment approach; (3) those with recurrent disease after a prolonged disease-free interval; and (4) patients who progress on first-line therapy. This article reviews the technical success rates, complications, and survival in patients undergoing these secondary cytoreductive procedures.


Current status of chemoprevention of head and neck cancer.

Chemoprevention involves efforts to block or reverse carcinogenesis before the development of invasive cancer. Natural agents, such as retinol and beta carotene, as well as synthetic retinoids have been studied as potential chemopreventive agents. In the head and neck, chemoprevention studies have included efforts both to reverse premalignant lesions such as oral leukoplakia and to prevent the development of second primary tumors. In one recent trial, high-dose 13-cis-retinoic acid treatment resulted in a dramatic reduction in the incidence of second primary tumors. However, significant toxicities were associated with the high dosage. This trial, as well as previous studies of oral leukoplakia, have led to the development of a chemoprevention trial using a low dose of 13-cis-retinoic acid to prevent second primary tumors following head and neck cancer. The rationale and design of this study are discussed in detail.


The presence of scatter factor in patients with metastatic spread to the pleura.

Pleural effusion fluid obtained from eleven patients with metastatic spread to the pleura was screened for the ability to cause the dispersal--'scattering'--of MDCK colonies in vitro. Four of these samples proved to be positive using this assay. Of these two had titres high enough to warrant further purification on a cation exchange Mono S column. Active material from both lung samples, eluted at the same positions as factor from cultured human lung fibroblasts (MRC-5) and human placenta but in a slightly different position to murine scatter factor. In both cases the semi-purified active agent was identified as hepatocyte growth factor/scatter factor (HGF/SF) using an ELISA detection system specific for human HGF/SF. This is the first report identifying the presence of significant amounts of HGF/SF in the pleura of patients where malignant spread has occurred.


Cyclophosphamide decreases O6-alkylguanine-DNA alkyltransferase activity in peripheral lymphocytes of patients undergoing bone marrow transplantation.

O6-alkylguanine-DNA-alkyltransferase (ATase) levels were measured in extracts of peripheral blood lymphocytes taken at various times during chemotherapy from 19 patients with various haematological malignancies. Seven patients with advanced Hodgkin's disease received preparative treatment consisting of cyclophosphamide (1.5 g m-2, daily) administered on days 1 to 4 and BCNU (600 mg m-2) on day 5 prior to autologous bone marrow rescue (ABMR) delivered on day 7. Treatment in the remaining 12 patients consisted of cyclophosphamide (1.8 g m-2, daily) given on days 1 and 2 followed at day 4 with total body irradiation (TBI) administered in six fractions over the subsequent 3 days to a total dose of 1200 cGy prior to bone marrow transplantation. In the Hodgkin's group, significant decreases in ATase activity were seen during the cyclophosphamide treatment, and the median ATase nadir was 32% (range 0% to 57%) of pretreatment levels following 4 days of cyclophosphamide. In one patient, no ATase activity was detectable following the 4th cyclophosphamide treatment. ATase activities decreased further after BCNU administration to a median of 19% (range 0% to 32%) of pretreatment levels. Extensive cyclophosphamide-induced reduction of lymphocyte ATase levels was also seen in the other group of 12 patients treated with cyclophosphamide/TBI: postcyclophosphamide median ATase nadir was 35% (range 12% to 78%) of the pretreatment levels. No ATase depletion was seen when cyclophosphamide (up to 10 mM) was incubated for 2 h with pure recombinant human ATase in vitro whereas ATase activity was reduced by 90% on preincubation with 100 microns acrolein or with greater than 1 mM phosphoramide mustard. This suggests that a cyclophosphamide-induced decrease in ATase levels in human peripheral lymphocytes in vivo may be due to depletion mediated by the production of intracellular acrolein. Since ATase appears to be a principal mechanism in cellular resistance to the cytotoxic effects of BCNU and related alkylating agents, these observations suggest that a cyclophosphamide-induced reduction in ATase activity may be an additional factor in the effectiveness of the combined sequential therapy.


Reconstitution of the sarcoplasmic reticulum Ca(2+)-ATPase: mechanisms of membrane protein insertion into liposomes during reconstitution procedures involving the use of detergents.

The Ca(2+)-ATPase from skeletal muscle sarcoplasmic reticulum was reconstituted into sealed phospholipid vesicles using the method recently developed for bacteriorhodopsin (Rigaud, J.L., Paternostre, M.T. and Bluzat, A. (1988) Biochemistry 27, 2677-2688). Liposomes prepared by reverse-phase evaporation were treated with various amounts of Triton X-100, octyl glucoside, sodium cholate or dodecyl octa(oxyethylene) glycol ether (C12E8) and protein incorporation was studied at each step of the liposome solubilization process by each of these detergents. After detergent removal by SM-2 Bio-Beads the resulting vesicles were analyzed with respect to protein incorporation by freeze-fracture electron microscopy, sucrose density gradients and Ca2+ pumping measurements. The nature of the detergent used for reconstitution proved to be important for determining the mechanism of protein insertion. With octyl glucoside, direct incorporation of Ca(2+)-ATPase into preformed liposomes destabilized by saturating levels of this detergent was observed and gave proteoliposomes homogeneous in regard to protein distribution. With the other detergents, optimal Ca(2+)-ATPase pumping activities were obtained when starting from Ca(2+)-ATPase/detergent/phospholipid micellar solutions. However, the homogeneity of the resulting recombinants was shown to be dependent upon the detergent used and in the presence of Triton X-100 or C12E8 different populations were clearly evidenced. It was further demonstrated that the rate of detergent removal drastically influenced the composition of resulting proteoliposomes: upon slow detergent removal from samples solubilized with Triton X-100 or C12E8, Ca(2+)-ATPase was found seggregated and/or aggregated in very few liposomes while upon rapid detergent removal compositionally homogeneous proteoliposomes were obtained with high Ca2+ pumping activities. The reconstitution process was further analyzed by centrifugation experiments and the results demonstrated that the different mechanisms of reconstitution were driven predominantly by the tendency for self-aggregation of the Ca(2+)-ATPase. A model for Ca(2+)-ATPase reconstitution was proposed which accounted for all our results. In summary, the advantage of the systematic studies reported in this paper was to allow a rapid and easy determination of the experimental conditions for optimal detergent-mediated reconstitution of Ca(2+)-ATPase. Proteoliposomes prepared by the present simple method exhibited the highest Ca2+ pumping activities reported to date in Ca(2+)-ATPase reconstitution experiments performed in the absence of Ca2+ precipitating agents.


Leukocytes in the intestinal epithelium: an unusual immunological compartment revisited.

Intraepithelial lymphocytes (IEL) are characterized by significant heterogeneity in morphology, surface antigen expression, and function. Although IEL can express T cell markers including the T cell receptor (TcR), their relationship to peripheral T cells is not clear. The finding of IEL in athymic nude mice first suggested that a number of IEL may be thymic-independent. The identification of the gamma/delta TcR heterodimer on IEL further suggested that these cells are part of a distinct population of epithelial-associated lymphocytes, many of which express the gamma/delta TcR. We review the nature of the V gamma gene usage in IEL and highlight the differences between different gamma/delta T cell populations. The thymic independent nature of these gamma/delta cells is discussed and compared to that of the alpha/beta TcR expressing IEL. The finding that some alpha/beta IEL can develop independent of thymic processing suggests that IEL are characterized by a unique collection of T cells that may undergo differentiation within the intestinal compartment. The ability to distinguish T-dependent from T-independent IEL raises the possibility of identifying the functional nature of these two IEL lineages. We propose that the ability of IEL to potentially undergo repertoire selection in the intestine could allow for the development of mucosal T cells uniquely adapted to function in this environment.


A prospective evaluation of the cumulative illness rating scale.

Assessment of overall physical health is an important yet little studied problem in geriatric research. The Cumulative Illness Rating Scale (CIRS) was among the first instruments that attempted to summarize the overall severity of illness based on clinical information. This study evaluated the CIRS in a prospective longitudinal study of 181 elderly (mean age +/- SD = 79 +/- 7.4) subjects undergoing comprehensive geriatric assessment in an outpatient unit. The CIRS was found to correlate negatively with activities of daily living (r = -0.49, p = 0.0001), instrumental activities of daily living (r = -0.34, p = 0.0001), patient morale (r = -0.30, p = 0.0001), and positively with days in hospital (r = 0.21, p = 0.0075) and number of medications (r = 0.31, p = 0.0001). Mean CIRS scores for subjects who died during follow-up were significantly higher than the scores for survivors (p less than 0.01). In logistic regression, CIRS was a significant predictor of death, yet it did not improve that prediction over information contained in measures of activities of daily living. In separate logistic analyses, CIRS and age predicted acute care hospital days during follow-up, while ADL or IADL predicted the use of nursing home services. Although the CIRS appears to be a reliable method of summarizing medical information and to have some external validity, in its present form it does not provide additional prognostic information.


Biochemical effects of human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the human neutrophil.

Through studies of the stimulus-response coupling of GM-CSF in the neutrophils, important clues to the nature of the signal transduction of GM-CSF receptors are starting to emerge. GM-CSF receptors which have to date been identified and characterized biochemically appear to be too small to contain internal tyrosine kinase domains. Nonetheless, tyrosine phosphorylation of five separate proteins results when neutrophils are incubated with GM-CSF (73). The most appealing explanation for this interesting observation is that one or more tyrosine kinases lie distal to GM-CSF receptors in their signal transduction pathway. While less likely, the possibility exists that another class of GM-CSF receptors which exhibit intrinsic tyrosine kinase activity remains to be identified. Characterization of the specific proteins which are phosphorylated on tyrosine residues ought to provide important insights into the signal transduction of this cytokine. On the other hand, direct activation of protein kinases C has not been observed following exposure of neutrophils to GM-CSF (19,22,80). GM-CSF induces the release of small quantities of arachidonic acid from the plasma membrane of the neutrophil (22). Arachidonic acid is primarily released directly through the effects of phospholipases A2 on membrane phospholipids or indirectly through activation of phospholipases C or D, which release compounds that can serve as a source of arachidonic acid when hydrolyzed by specific enzymes. Direct activation of phospholipases C in the neutrophil by GM-CSF appears most unlikely, since GM-CSF does not elevate [Ca2+]i or induce the release of detectable quantities of inositol trisphosphates or diacylglycerols in these cells. Therefore, the possibility that GM-CSF may directly activate phospholipases A2 is quite plausible. GM-CSF directly activates Na+/H+ antiporters in the plasma membrane of the neutrophil, resulting in alkalinization of the cytoplasm of approximately 0.1-0.25 pH unit (73). The function of cytoplasmic alkalinization in the priming of mature neutrophils is unclear. However, evidence exists in other cell systems that cytoplasmic alkalinization may be important in inducing cell proliferation, since the pH optima of several enzymes necessary for DNA synthesis are slightly more alkaline than the resting pH of the cytosol. Many types of growth factors which initiate cell division through occupancy of surface receptors give rise to cytoplasmic alkalinization through just such a mechanism (52). Therefore, it seems likely that GM-cSF may activate Na+/H+ antiporters in the plasma membranes of hemic progenitor cells which bear GM-CSF receptors and which proliferate in response to this cytokine.(ABSTRACT TRUNCATED AT 400 WORDS)


[Hemostatic disorders following polytrauma--the role of physiologic coagulation inhibitors during the preclinical phase].

Coagulation changes due to polytrauma are considered to be an important determinant for the outcome. In this context, physiological inhibitors of activated coagulation are highlighted with special reference to antithrombin-III (AT-III). Blood samples of 20 randomly selected adults with polytrauma (Injury Severity Score mean = 36.7 +/- 8.6) were investigated. To investigate the very early onset of coagulation changes, samples were taken as early as possible at the site of emergency (mean = 18.3 +/- 5.5 min. after trauma) as well as at hospital admission (mean = 78.0 +/- 10.4 min.). By means of a specially designed "mini-lab", basic processing of the samples harvested (centrifugation, pipetting, freezing) was done on the spot to obtain haemostaseological results that agree as closely as possible with the subsequent analyses. Due to the activation of intravascular coagulation as well as the consumption of physiological inhibitors, comprehensive coagulation disturbances become obvious at the time of hospital admission. These are intensified by haemodilution as a consequence of high-dose fluid replacement. However, significantly elevated levels of specific coagulation reaction products (thrombin-antithrombin-III-complex) give evidence of the consumption of inhibitory potential exceeding haemodilution.


Bioelectrorheological model of the cell. 3. Viscoelastic shear deformation of the membrane.

An analytical electromechanical model of a spherical cell exposed to an alternating electric field was used to calculate shear stress generated in the cellular membrane. Shape deformation of Neurospora crassa (slime) spheroplasts was measured. Statistical analysis permitted empirical evaluation of creep of the cellular membrane within the range of infinitesimal stress. Final results were discussed in terms of various rheological models.


Injectable and implantable contraceptives.

In December 1990, the Food and Drug Administration approved Norplant (Wyeth-Ayerst, Radnor, PA) for general US use. This approval comes during a time period when the number of contraceptors relying on sterilization has risen, echoing known dissatisfaction with other reversible methods. During the past year, data have been presented that refute concern that Norplant may be an abortifacient. Continued estradiol production with development of follicles and ovulation in regularly menstruating women was documented. Ovulatory dysfunction among Norplant users, despite follicular development, was also detailed. Changes in carbohydrate metabolism were confirmed to be clinically insignificant. International development of biodegradable and non-biodegradable implants and 1, 3, or 6 months injectables continues. These injectable and implantable contraceptives promise diversity in contraceptive options to match diversity in contraceptive need and life style.


Prevalence of spinal pain among the staff of a district health authority.

Being aware of the many neck and back problems which occur among staff, the departments of Occupational Medicine and Physiotherapy initiated a study to ascertain the scale of the problem among employees of the district health authority. A questionnaire was sent to a 10 per cent sample, stratified by occupation, of the 16,000 employees of a district health authority of which 84 per cent (1363) responded. Over half of all respondents had had a significant degree of spinal pain in the past year, mainly located in the back. In over half of those with pain, their discomfort had been significant enough to interfere with sport, work and sleep. Over one-quarter said they had taken time off work for spinal pain in the past five years. Nearly half of respondents under 25 years of age had some degree of spinal pain. Although a very small group, ambulance workers appear to have the greatest problems. Staff involved in lifting equipment and manual work had a lower prevalence of spinal pain than nurses or ambulance workers, but were more likely to have severe pain for which analgesics were taken. Nurses had a prevalence rate of 60 per cent, but less than one third had frequent or severe pain. Based upon this information an application has been made to implement a programme to reduce both the number of injuries and the severity of those that occur.


Cardiovascular and sympathetic nervous response to dynamic exercise in patients with essential hypertension.

To investigate the relationship among systolic blood pressure (SBP) during exercise (EX), left ventricular hypertrophy (LVH) and plasma norepinephrine concentration (NE) in patients with essential hypertension (HT), 20 patients with HT and 20 age- and sex-matched normal subjects were studied using treadmill testing. According to the change in SBP from rest to EX (delta SBP), patients with HT were classified into two groups (group I, n = 12, delta SBP less than 72 mmHg: group II, n = 8, delta SBP greater than or equal to 72 mmHg). There were no significant differences between the two groups with regard to SBP at rest, NE at rest and NE on EX. However, SBP at peak EX, delta SBP and the incidence of LVH were greater in group II than in group I. We conclude that exaggerated SBP response to EX in patients with HT is related to LVH.


Angiotensin II receptor antagonist losartan has persistent effects on blood pressure in the young spontaneously hypertensive rat: lack of relation to vascular structure.

The persistent effects on blood pressure of the angiotensin II receptor antagonist losartan and the converting enzyme inhibitor captopril were compared in the young spontaneously hypertensive rat (SHR). Losartan (DuP753/MK954, 15 mg/kg/day) and captopril (100 mg/kg/day) were given in the drinking water of 3-week-old SHRs for 4- and 10-week durations. Blood pressure was measured during treatment and after treatment was stopped until the age of 30 weeks. Both losartan and captopril given for 4 and 10 weeks prevented the development of hypertension during treatment and redevelopment of hypertension after treatment was stopped. Treatment for 10 weeks was more effective than for 4 weeks in lowering long-term pressure. Four weeks of treatment did not affect the mesenteric resistance artery media/lumen (m1/l1) ratio. In contrast, both losartan and captopril given for 10 weeks resulted in large and significant reductions in m1/l1 [5.3 +/- 0.8 and 5.63 +/- 0.8 vs 7.7 +/- 0.8 x 10(-2) (SD), p less than 0.001]. In losartan-treated rats, plasma renin and angiotensin II concentration were increased between 4- and 7-fold at the end of both treatment periods. These findings show losartan to be an effective antihypertensive agent and support data implicating angiotensin II in the early events leading to hypertension in this model. The abilities of losartan and captopril to affect blood pressure without affecting vascular structure suggest that the latter is a poor predictor of long-term hypertensive levels in the SHR.


[A preliminary study on the red cell immune function in blood stasis syndrome in traditional Chinese medicine].

20 patients with blood stasis syndrome (BSS), 20 patients with non-blood stasis syndrome (NBSS), and 17 normal subjects were measured by tests of RBC-C3b receptor rosette and RBC immune complex rosette. The rates of RBC-C3b receptor rosette formation (RBC-C3b RR, %) in BSS group, NBSS group and normal subjects were 20.90 +/- 4.02, 12.88 +/- 3.29 and 16.74 +/- 4.13 (P less than 0.01) respectively. The rates of RBC immune complex rosette formation (RBC-IC R, %) in the three groups were respectively 8.28 +/- 3.68, 7.73 +/- 2.48 and 7.41 +/- 2.43 (P less than 0.05). RBC-C3b RR was correlated to RBC-IC R in the normal subjects (r = 0.695, P less than 0.001). In patients with the same disease, RBC-C3b RR between the two syndromes (BSS and NBSS) was also very significantly different (P less than 0.01). This study suggested that there are variations on red cell immune function in BSS patients, and also provided an evidence that different syndromes of traditional Chinese medicine exist in diseases.


Eicosanoid-dependent and endothelium-independent oscillations of rat aorta.

We studied the role of endothelium and eicosanoids in rhythmic contractions of rat thoracic aorta. Spontaneous oscillations were observed in 35% of 385 endothelium-intact and in 46% of 22 endothelium-denuded aortic strips from normotensive Sprague-Dawley male rats. Vasoactive agents (norepinephrine, epinephrine, phenylephrine, isoproterenol, arachidonic acid, PGF2 alpha, serotonin, potassium, endothelin, atrial natriuretic factor and angiotensin II) induced rhythmic contractions in the majority of tissues. Rhythmic activity was also observed in aortic strips from adult female, pregnant and old male rats. Aortic oscillations were partially inhibited by indomethacin, ibuprofen and nordihydroguaiaretic acid (NDGA), and completely inhibited by indomethacin plus NDGA, nifedipine, low external calcium (less than 1 mM) and pretreatment with dexamethasone. Indomethacin, NDGA and arachidonic acid did not affect oscillations of the portal vein. Rhythmic contractions were observed in thoracic aortic strips from neonatal but not from adult rabbits. However, oscillations could be induced in strips of the mesenteric artery and terminal abdominal aorta of adult rabbits. Also, adult rabbit thoracic aortic strips exhibited oscillations when set up in close proximity of rat aorta. It is suggested that rhythmic contractions are physiological characteristics of many and perhaps all blood vessels and may play a role in blood flow and turbulence; the likely cause of these oscillations is the cyclic release of one or more eicosanoids.


Ultracytochemical demonstration of Ca(++)-ATPase activity in the rat cardiac muscle.

Ca(++)-activated adenosine triphosphatase (Ca(++)-ATPase) was investigated in the rat cardiac muscle at neutral pH using tricine buffer. Reaction products indicating Ca(++)-ATPase activity were localized on the myocardial sarcolemma, sarcoplasmic reticulum, myofilaments, luminal and abluminal surfaces of capillary endothelium plasmatic membrane. The verification of the main enzymatic characteristics of Ca(++)-ATPase localization activity using this cytochemical procedure is under discussion.


Effect of CD23 on purified human hematopoietic cells.

We report herein the effect of soluble CD23 (sCD23) on the differentiation of lymphoid and myeloid precursors. CD23 is known as the low affinity receptor for IgE. In addition to it, our results indicate that sCD23 in synergy with IL1 is able to promote the maturation of normal and leukemic hematopoietic progenitor cells.


Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist.

1. OPC-31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2. OPC-31260 caused a competitive displacement of [3H]-AVP binding to both V1 and V2 receptors with IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x 10(-8) M, respectively. 3. OPC-31260 at doses of 10 to 100 micrograms kg-1, i.v., inhibited the antidiuretic action of exogenously administered AVP in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a partial V2 receptor agonist. 4. After oral administration at doses of 1 to 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC-31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5. The results indicate that OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention.


Neuroendocrine response to clonidine and 8-OH-DPAT in rats following chronic administration of desipramine or sertraline.

1. Rats were administered either desipramine (DMI) or sertraline daily at doses 7.5 mg kg-1 or 10 mg kg-1, i.p., respectively and the effects on the functional state of hypothalamic neuroendocrine control mechanisms assessed by measurements of plasma hormones following acute drug challenge. The effects of treatment on gross behaviour and brain adrenoceptor density were also determined. 2. Both DMI and sertraline caused significant reduction in activity measured as ambulation and rearing at 14 days of treatment. 3. All animals were chronically cannulated after 14 days of treatment and tested for neuroendocrine response to acute i.v. clonidine (50 micrograms kg-1) or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 250 micrograms kg-1) after 21 or more days of treatment. 4. Rats treated with DMI but not sertraline showed a virtually complete suppression of the growth hormone (GH) secretion elicited by clonidine in controls, while the secretion of corticosterone was augmented. 5. Treatment with DMI but not sertraline led to a significantly greater 8-OH-DPAT-induced secretion of prolactin than in the control rats, while the plasma concentrations of corticosterone following 8-OH-DPAT were not influenced by either DMI or sertraline treatment. 6. The density (but not the affinity) of cerebral cortical binding of [3H]-dihydroalprenolol was significantly reduced by DMI treatment. 7. These results show that DMI treatment blunted the sensitivity of post-synaptic alpha 2-adrenoceptors, accompanied by complex interactions manifested as increased responsiveness of alpha 1-adrenoceptors and 5-HT1A receptors. Sertraline had no significant neurendocrine effects at a dose which significantly reduced gross activity.


Effects of monoamine uptake inhibitors on extracellular and platelet 5-hydroxytryptamine in rat blood: different effects of clomipramine and fluoxetine.

1. The concentration of 5-hydroxytryptamine (5-HT) in rat platelet-free plasma increased significantly 30 min after a single i.p. injection (10 mg kg-1) of each of six inhibitors of the high-affinity 5-HT uptake (fluvoxamine, fluoxetine, alaproclate, paroxetine, sertraline and clomipramine). The increases ranged from 226% to 776% of control values. In contrast, imipramine, desipramine and femoxetine had no significant effect. The increase elicited by paroxetine was dependent on the dose (1, 5 and 10 mg kg-1) and returned to control values after 4 h. That observed after clomipramine was also transient and paralleled the plasma concentration of the drug (Spearman-rank correlation r = 0.43). 2. In vivo, the rat pulmonary vascular endothelium removed trace amounts (8.8 nmol in a bolus) of intravenously injected [14C]-5-HT. Paroxetine pretreatment (10 mg kg-1, 30 min before-hand) reduced this uptake by 73%. 3. Repeated fluoxetine treatments reduced rat whole blood 5-HT concentration (ca. -60% after daily 2 x 5 mg kg-1, i.p. during 14 days). However, plasma (extracellular) 5-HT was not increased. 4. Various repeated treatments with clomipramine (i.p. injections or osmotic minipumps, up to 30 mg kg-1 day-1), failed to decrease rat whole blood 5-HT concentrations. Platelet-free plasma 5-HT was also unchanged, even after treatments yielding plasma clomipramine levels 2.7 times higher than those that increased it acutely. 5. These results indicate that the extracellular pool of 5-HT in rat blood (measured in the platelet-free plasma) is physiologically under the control of high-affinity 5-HT uptake systems.The sustained 5-HT uptake inhibition does not result in an increase of 5-HT in platelet-free plasma, suggesting that adaptative mechanisms are triggered. The distinct long-term effects of the two antidepressants clomipramine and fluoxetine on rat whole blood 5-HT suggest a differential in vivo action on the rat 5-HT uptake.


Effects of the neutral endopeptidase inhibitor, SQ 28,603, on regional haemodynamic responses to atrial natriuretic peptide or proendothelin-1 [1-38] in conscious rats.

1. Regional haemodynamic responses to atrial natriuretic peptide (ANP, 0.5 nmol kg-1) or proendothelin-1 [1-38] (1.0 nmol kg-1) were assessed in the same conscious Long Evans rats before and 20 min after administration of the novel neutral endopeptidase (NEP) inhibitor, SQ 28,603 (50 mg kg-1, i.v.). In a separate experiment, responses to endothelin-1 (0.5 nmol kg-1), angiotensin I (0.25 nmol kg-1) and angiotensin II (0.12 nmol kg-1) were measured before and after administration of SQ 28,603. 2. SQ 28,603 alone had no significant cardiovascular effects but caused significant prolongation of the hypotensive, tachycardic and renal and mesenteric vasoconstrictor effects of ANP. However, the early vasodilator and late vasoconstrictor responses in the hindquarters were not affected significantly. 3. SQ 28,603 caused significant attenuation of the pressor effects of proendothelin-1 [1-38] but the associated bradycardia was unchanged. SQ 28,603 caused a significant inhibition of the renal and mesenteric vasoconstrictor effects of proendothelin-1 and also inhibited the initial vasodilator and subsequent vasoconstrictor responses in the hindquarters vascular bed. 4. SQ 28,603 had no significant effects on the haemodynamic responses to endothelin-1, angiotensin I, or angiotensin II. 5. The results are consistent with SQ 28,603 not only inhibiting NEP that is involved in the degradation of ANP, but also suppressing activity of the enzyme involved in the conversion of proendothelin-1 [1-38] to endothelin-1.


Effects of cyclopiazonic acid, a novel Ca(2+)-ATPase inhibitor, on contractile responses in skinned ileal smooth muscle.

1. Effects of cyclopiazonic acid (CPA), a specific inhibitor of the Ca(2+)-ATPase in sarcoplasmic reticulum (SR) of skeletal and cardiac muscles, on contractile responses induced by Ca(2+)-release from intracellular storage sites were examined in the longitudinal smooth muscle strip of the guinea-pig ileum skinned with beta-escin. 2. Ca(2+)-loading of storage sites (Ca(2+)-uptake) was performed in pCa 6.3 solution. The amount of Ca2+ taken up was monitored by use of the amplitude of contraction following application of 25 mM caffeine or 25 microM inositol 1,4,5-trisphosphate (IP3). 3. Contractile responses to caffeine or IP3 were reduced or abolished when the preceding Ca(2+)-uptake was performed in the presence of 0.1-10 microM CPA. The dose of CPA required to inhibit the contraction induced by caffeine or IP3 by 50% was approximately 0.6 microM. The CPA-sensitive Ca(2+)-uptake completely depended upon the presence of ATP in the solution during Ca(2+)-uptake. 4. When 1 microM CPA was added after Ca(2+)-uptake, the subsequent caffeine- or IP3-induced contraction was not significantly affected by the presence of CPA. 5. Acetylcholine-induced contraction was also almost abolished when the preceding Ca(2+)-uptake was performed in the presence of 10 microM CPA. 6. The relationship between pCa and contraction was not affected by the presence of 10 microM CPA in skinned fibres where Ca2+ storage sites had been destroyed by treatment with A23187. The enhancement of contraction in pCa 6.0 solution by calmodulin was not affected by 10 microM CPA.7. These results suggest that CPA selectively inhibits ATP-dependent Ca2"-uptake into intracellular storage sites in skinned ileal smooth muscle strips. CPA appears to be a potent, reversible, and very specific inhibitor of the Ca2+-pump in the storage sites of smooth muscle, and is an extremely valuable pharmacological tool.


Effects of vapiprost, a novel thromboxane receptor antagonist, on thrombus formation and vascular patency after thrombolysis by tissue-type plasminogen activator.

1. A thrombus was induced in the rat femoral artery by endothelial damage due to the photochemical reaction between systemically-injected Rose Bengal and transillumination with green light (wavelength: 540 nm). The artery of the control rat was completely occluded in 302.8 +/- 27.0 s after the initiation of the reaction. 2. Pretreatment with vapiprost (0.1, 0.3 and 1.0 mg kg-1, i.v., 5 min before the reaction) prolonged the time required to occlude the femoral artery in a dose-dependent manner. The efficacy of vapiprost on the time required for occlusion was over 10 times higher than that of aspirin which was administered 30 min before the reaction. 3. The thrombolytic effects of tissue-type plasminogen activator (tPA) on the established arterial thrombus in the presence and absence of vapiprost were also studied in the same model. When vapiprost (0.3 mg kg-1, i.v.) was administered just before tPA infusion (100 micrograms kg-1 min-1 for 30 min), the time required to reperfuse the occluded artery was reduced, the incidence of the reperfusion was increased and the arterial blood flow after reperfusion was improved. 4. When vapiprost (1.0 mg kg-1 daily p.o.) was administered for 1 week after the establishment of reperfusion by tPA combined with vapiprost, the patency of the reperfused artery was improved and the femoral arterial blood flow was better preserved than after treatment with only tPA. 5. These findings suggest that this thromboxane receptor antagonist may be a useful adjunct to anti-thrombotic therapy. The combination therapy with tPA may be more effective than treatment with tPA alone and provides greater protection against reocclusion after reperfusion.


Pharmacological characterization of 5-hydroxytryptamine-induced excitation of afferent cervical vagus nerve in anaesthetized rats.

1. An excitatory response to 5-hydroxytryptamine (5-HT) was measured from the afferent vagus nerve of anaesthetized rats. Measurements were determined by an extracellular recording from the whole nerve. 2. Intravenous bolus injection of 5-HT (1.56-100 micrograms kg-1) evoked a dose-dependent excitation of afferent vagus nerve activity. This response was blocked not only by a selective 5-HT3 receptor antagonist, GR38032F (10 and 100 micrograms kg-1), but also by a 5-HT2 receptor antagonist, ketanserin (10 and 100 micrograms kg-1). 3. Both a 5-HT3 receptor agonist, 2-methyl-5-HT (3.12-100 micrograms kg-1), and a 5-HT2 receptor agonist, alpha-methyl-5-HT (3.12-50 micrograms kg-1), produced a dose-dependent excitation of afferent vagus nerve activity. These excitatory effects were antagonized by GR38032F (10 micrograms kg-1) and ketanserin (10 micrograms kg-1), respectively. 4. A 5-HT1 like receptor agonist, 5-carboxamidotryptamine (50 micrograms kg-1), and a putative 5-HT4 receptor agonist, 5-methoxytryptamine (100 micrograms kg-1), failed to produce excitatory effects on the afferent vagus nerve. 5. These results suggest that the 5-HT-induced excitatory response of the afferent vagus nerve might be mediated not only via 5-HT3 receptors but also via 5-HT2 receptors in anaesthetized rats. It is unlikely, however, that either 5-HT1-like or putative 5-HT4 receptors are involved in the excitatory response of the afferent vagus nerve to 5-HT.


Effects of interleukin-1 receptor antagonist on the behavioral effects of lipopolysaccharide in rat.

To investigate the role of interleukin-1 (IL-1) in lipopolysaccharide (LPS)-induced sickness behavior, rats were injected with recombinant human interleukin-1 receptor antagonist (IL-1ra), an endogenous cytokine able to block most of the biological effects of IL-1 both in vivo and in vitro. Intraperitoneal injection of IL-1ra (3 mg/rat) attenuated the depressive effect of LPS (250 micrograms/kg) on social exploration and body weight when both treatments were injected peripherally. Intracerebroventricular injection of IL-1ra (60 micrograms/rat) did not block the effects of peripherally injected LPS. These data indicate that the peripherally mediated effects of IL-1 account for a significant part of LPS-induced sickness behavior.


Evidence for postsynaptic mediation of the hypothermic effect of 5-HT1A receptor activation.

1. The 5-HT1A ligand BMY 7378 (8-[2[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]8-azaspirol [4,5]-decane-7,9-dione dihydrochloride, 0.032-2 mg kg-1, s.c.) caused hyperphagia, a response to the activation of presynaptic 5-HT1A receptors. 2. BMY 7378 (8 mg kg-1, s.c.) and the 5-HT1A agonist (8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), 0.10 and 0.25 mg kg-1 s.c.) also caused hypothermia. This was inhibited by (-)-pindolol (1-mg kg-1, i.p.) and not prevented by pretreatments with p-chlorophenylalanine which grossly depleted 5-hydroxytryptamine (5-HT) from terminal regions. The hypothermic effects are explicable by activation of postsynaptic 5-HT1A receptors. Infusion of BMY 7378 (8-64 micrograms) into the dorsal raphe was without convincing hypothermic effect. 3. BMY 7378 (8 mg kg-1, s.c.) inhibited another effect of activation of postsynaptic 5-HT1A receptors, i.e., the induction of components of the 5-HT syndrome by 8-OH-DPAT (0.5, 1.0 mg kg-1, s.c.) which suggests that BMY 7378 has antagonistic as well as agonistic effects at these sites. 4. Partial agonist properties of BMY 7378 at postsynaptic sites were also indicated by doses for hypothermia being much greater than those for hyperphagia i.e., ED50 (hypothermia) greater than 2 mg kg-1, ED50 (hyperphagia) = 0.010 mg kg-1. This contrasts with the similar ED50 values for both the hypothermic (ED50 = 0.08-0.10 mg kg-1) and hyperphagic (ED50 = 0.06-0.10 mg kg-1) effects of 8-OH-DPAT.5. The evidence obtained for mediation of the hypothermic response to 5-HTIA agonists by postsynaptic sites is relevant to the interpretation of the effects on it of antidepressant treatments and depressive illness.


The combination of NMDA antagonism and morphine produces profound antinociception in the rat dorsal horn.

Dorsal horn nociceptive neurones exhibit wind up, a frequency dependent potentiation of their responses to repeated C-fibre stimulation. Intrathecal morphine (5 micrograms) significantly reduces the initial responses of the neurones but not wind up whereas the reverse is true for N-methyl-D-aspartate (NMDA) antagonists. The combination of intrathecal morphine (5 micrograms) and 7-chlorokynurenate (2.5 micrograms), an antagonist at the glycine site of the NMDA receptor, abolishes both the input and wind up of these neurones.


Cocaine-induced behavioral sensitization and D1 dopamine receptor function in rat nucleus accumbens and striatum.

Based on electrophysiological data showing that repeated cocaine administration produces persistent enhancement of D1 dopamine (DA) receptor-mediated responses in nucleus accumbens (NAc), we investigated whether changes in neurochemical properties of these receptors resulted when rats were injected with cocaine (15 mg/kg) for 6 days followed by a 7-day abstinence period. D1 DA receptor density and affinities for either [3H]SCH 23390 or DA were similar between NAc and striatum and between saline and cocaine treatment groups. DA-stimulated adenylyl cyclase activity was 1.5-fold higher in striatum than in NAc; however, repeated cocaine treatment produced no persistent changes in enzyme activity in either brain area.


Autoradiographic localization of dopamine D1 and D2 receptors in rat cerebral cortex following unilateral neurotoxic lesions.

Relative to dopaminergic innervation of cortex, dopamine D1 and D2 receptors may be located on presynaptic terminals and/or postsynaptically on cortical neurons. To assess the relative distribution of these sites, quantitative in vitro receptor autoradiography was performed following injection of 6-hydroxydopamine (6-OHDA) into the median forebrain bundle (MFB; which lesions presynaptic DA terminals) and ibotenic acid into the prefrontal and anterior cingulate cortices (which lesions neurons whose cell bodies are intrinsic to cortex). Receptor autoradiography was performed ten days after injection of neurotoxins with [3H]SCH 23390 (a D1 probe) and [125I]epidepride (a D2 probe). Both DA receptor subtypes were found in all layers of anterior cingulate and prefrontal cortices but were concentrated in deeper layers V and VI. Ibotenic acid lesion of cortex reduced D1 and D2 receptors by 55-80%, although the concentrations of DA and its major metabolite dihydroxyphenylacetic acid (DOPAC) were unchanged. Lesion of MFB produced no significant change in D1 and D2 receptors, but was associated with a 49-52% decrease in DA and DOPAC levels relative to the contralateral side. These results suggest that the majority of D1 and D2 receptors in prefrontal and anterior cingulate cortices are located postsynaptically on neurons intrinsic to the cortex.


D1 and D2 receptor modulation in rat striatum and nucleus accumbens after subchronic and chronic haloperidol treatment.

The antipsychotic effects of neuroleptic drugs are believed to be achieved by chronic blockade of dopaminergic transmission in the limbic system. Nevertheless, the effects of chronic (3-12 months) haloperidol administration on the dopaminergic transmission in the nucleus accumbens of rodents remains poorly understood. Studies of spontaneous locomotor activity (SLA), a behavioral measure related to limbic dopamine transmission, and of dopamine D2 receptor density in the nucleus accumbens after chronic oral haloperidol treatment have yielded conflicting results. We evaluated these indices after 8 months of parenteral administration of haloperidol decanoate. We report here that, after 8 months of parenteral treatment, SLA stays significantly decreased and D2 receptors in the nucleus accumbens exhibit the same up-regulation as in the striatum (about 50%). These results fail to support the notion of a different pattern of D2 receptor adaptation to neuroleptic treatment between the nucleus accumbens and the striatum. In contrast, dopamine D1 receptors were found to be unaffected in the nucleus accumbens but decreased in the striatum by 22% after 8 months of treatment. This observation could be relevant to the pathogenesis of tardive dyskinesia.


Post-lesion administration of the NMDA receptor antagonist MK-801 does not impair motor recovery after unilateral sensorimotor cortex injury in the rat.

Although treatment with N-methyl-D-aspartate (NMDA) receptor antagonists reduce neuronal loss after cerebral infarction and brain trauma in laboratory animals, there is little data concerning the effects of these drugs on behavioral recovery. Because NMDA receptor antagonists impede certain kinds of learning, and because motor recovery after sensorimotor cortex injury in the rat is dependent on post-lesion experience, we hypothesized that treatment with MK-801 after focal brain injury would be detrimental. Groups of rats were first trained to traverse a narrow elevated beam and then subjected a right sensorimotor cortex suction-ablation lesion. In the first experiment, 24 h later, each rat received a single dose of either saline or the NMDA receptor antagonist MK-801 (0.5, 1.0, or 2.0 mg/kg). Beam-walking recovery was measured over the next 12 days. In a second experiment, rats were given 3 doses of MK-801 (0.5 mg/kg) at 24 h intervals beginning 24 h after cortex injury. In a third experiment, lesioned and sham-operated rats were allowed to recover for 12 days and then given MK-801 (0.5 mg/kg). Despite obvious behavioral effects of the drug, there was no overall difference in beam-walking performances among the treatment groups in any of the experiments. If 're-learning' is involved in motor recovery after cortex injury, the present results suggest that the process is not susceptible to permanent disruption by the early or late administration of an NMDA receptor antagonist.


A comparison of the effects of the 5-HT1 agonists TFMPP and RU 24969 on feeding following peripheral or medial hypothalamic injection.

Experiments were conducted to compare the food intake suppressant effects of the 5-hydroxytryptamine (5-HT)1 agonists 1-3-trifluoromethylphenylpiperazine hydrochloride (TFMPP) and 5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)1H indole (RU 24969) following either peripheral or medial hypothalamic injections. The effects of these manipulations were examined in 3 different paradigms involving the stimulation of feeding by: (1) infusion of 25 nmol noradrenaline (NA) into the medial hypothalamus, (2) adaptation to a 20 h food deprivation schedule, and (3) the presentation of a palatable wet mash diet for 1 h each day to ad libitum-fed rats. In all 3 paradigms TFMPP and RU 24969 (0.31-5 mg/kg, i.p.) induced dose-dependent reductions of food intake. Both drugs were somewhat less potent at inhibiting feeding that resulted from food deprivation. In contrast to these results medial hypothalamic infusion of TFMPP or RU 24969 (12.5-50 nmol) failed to affect food intake in any of the 3 tests. This occurred in spite of the fact that both 5-HT (12.5-50 nmol) and fluoxetine (12.5-50 nmol) mildly attenuated the feeding that resulted from NA infusion into the same site. The results provide clear evidence that the food intake suppressant effects of peripherally injected TFMPP and RU 24969 are not mediated in the medial hypothalamus. They also suggest that even though manipulations of serotonergic function within the medial hypothalamus can alter food intake, this probably does not involve selective activation of 5-HT1C and/or 5-HT1B receptors.


Reduced density of NMDA receptors and increased sensitivity to dizocilpine-induced learning impairment in aged rats.

About 20 min prior to training in a shock-motivated 14-unit T-maze, young (3-4 months) and aged (24-25 months) male Fischer-344 rats were given s.c. injections of either saline or dizocilpine (MK-801, 0.02 or 0.04 mg/kg), a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. The aged rats showed a dose-dependent impairment in maze performance. Deficiencies were manifested as increases in errors, in runtime from start to goal, and in the number and duration of shocks received. In contrast, young rats exhibited no detrimental effects of dizocilpine on maze performance. Analysis of [3H]glutamate binding in these rats revealed a marked age-related decline in NMDA receptor binding in hippocampus. A significant correlation was observed between errors in the maze and hippocampal [3H]-glutamate binding, but the correlation was positive, i.e., rats that made the most errors had the highest level of NMDA receptor binding. Thus, compared to young rats, aged rats were more sensitive to the behavioral effects of NMDA receptor antagonism and they showed a hippocampal loss of [3H]glutamate in binding, which may be related to the increased sensitivity to dizocilpine. The positive correlation between poor maze performance and NMDA receptor binding suggests that the behaviors assessed involve complex interactions between NMDA receptors and other neuronal systems in the hippocampus.


Impairment of endothelium-dependent dilatation of the basilar artery during diabetes mellitus.

The goal of this study was to determine whether responses of the basilar artery are altered during diabetes mellitus. We measured the diameter of the basilar artery in vivo in non-diabetic and diabetic rats (streptozotocin; 50-60 mg/kg i.p.). Responses of the basilar artery to agonists, which presumably produce dilatation by releasing endothelium-derived relaxing factor (EDRF), were impaired in diabetic rats compared to non-diabetic rats. Acetylcholine (1.0 and 10 microM) dilated the basilar artery by 13 +/- 2 and 26 +/- 4% (means +/- S.E.M.), respectively, in non-diabetic rats, but by only 4 +/- 1 and 9 +/- 2%, respectively, in diabetic rats (P less than 0.05). Bradykinin (1.0 and 10 microM) dilated the basilar artery by 14 +/- 2 and 35 +/- 6% (means +/- S.E.M.), respectively, in non-diabetic rats, but by only 5 +/- 1 and 6 +/- 2%, respectively, in diabetic rats (P less than 0.05). The response to nitroglycerin was similar in non-diabetic and diabetic rats. Thus, impairment of vasodilatation in diabetic rats in response to acetylcholine and bradykinin is not related to non-specific impaired of vasodilatation. Next, we examined the possibility that impaired dilator responses of the basilar artery in response to acetylcholine and bradykinin in diabetic rats may be related to the activation of the thromboxane A2-prostaglandin H2 receptor. SQ 29548 (a specific thromboxane A2-prostaglandin H2 receptor antagonist) did not alter responses of the basilar artery to acetylcholine and bradykinin. These findings suggest that diabetes mellitus impairs endothelium-dependent dilatation of the basilar artery.(ABSTRACT TRUNCATED AT 250 WORDS)


Decreased brain N-acetylaspartate in Huntington's disease.

The concentration of N-acetylaspartic acid (NAA) was measured in perchloric acid extracts of postmortem brain tissue obtained from patients with Huntington's disease and from control subjects. The material in the desalted extracts was resolved on an ion exclusion column and the content of NAA was determined by subsequent fluorometric quantitation of aspartate in hydrolyzates of the resolved NAA. The concentration of NAA in the putamen from patients with Huntington's disease was less than half that of controls (2.74 vs. 6.06 mumol/g wet weight). A smaller but significant reduction was also evident in samples of cerebral cortex from Brodmann area 10 (3.99 vs. 5.29 mumol/g), while the difference in concentrations in the cerebellum was not statistically significant. Though NAA could play a direct role in Huntington's disease, it seems more likely that the changes observed reflect illness or death of neurons, and that it may be feasible to monitor the course of Huntington's disease from NAA determinations. The same tissue extracts were also examined for the presence of D-isomers of amino acids. Only traces were found in NAA, aspartate, or glutamate.


Effects of the N-methyl-D-aspartate antagonists on the rise in [Ca2+]i following depolarization in aged rat brain synaptosomes.

The effects of non-competitive NMDA antagonists, MK-801 and dextrorphan in relation to the rise in intracellular Ca2+ concentrations ([Ca2+]i) after stimulation with 15 mM K+ in whole brain synaptosomes from young (3 months old) and aged (24 months old) Fisher344 rats were examined. A fluorescent chelating agent, Rhod-2, was employed to monitor any alterations of K(+)-evoked [Ca2+]i. In young rats, the rise in [Ca2+]i following depolarization was affected by neither dextrorphan (1, 10, 100 microM) nor MK-801 (0.1, 1, 10 microM), while in aged rats, 1 microM dextrorphan and 0.1 microM MK-801 brought about a significant increase in [Ca2+]i following depolarization. In low Mg2+ medium, 10 microM MK-801 and 100 microM dextrorphan significantly inhibited the rise in [Ca2+]i after stimulation with 15 mM K+ in young rats, while neither dextrorphan nor MK-801 could affect the rise in [Ca2+]i significantly in aged rats. When 100 microM NMDA was applied in a medium containing 1.2 mM Mg2+, the rise in [Ca2+]i following depolarization was slightly inhibited by 1 microM MK-801 in young rats, but it was not inhibited significantly by dextrorphan. In aged rats, both 100 microM dextrorphan and 10 microM MK-801 strongly inhibited the rise in [Ca2+]i following depolarization in the presence of 100 microM NMDA. Instead of NMDA, when 100 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), a non-NMDA receptor agonist, was applied, dextrorphan did not inhibit the rise in [Ca2+]i. In low Mg2+ medium, 100 microM NMDA potentiated the inhibitory effect of 10 microM dextrorphan in young rats, while 100 microM dextrorphan or MK-801 did not show any further inhibition by adding 100 microM NMDA. The addition of 100 microM AMPA did not affect the effect of dextrorphan in a low Mg2+ medium in young rats. These results suggest that NMDA antagonist-mediated [Ca2+]i homeostatic system may alter through aging. In addition, the findings that NMDA potentiated the inhibitory effect of NMDA antagonist, which being further potentiated by aging or lowered extrasynaptosomal Mg2+, indicate the possibility that the Mg2+ block to NMDA receptors might be attenuated through aging.


Assessment of the need for education and/or training in the dental care of people with handicaps.

A survey questionnaire was sent to members of the British Society of Dentistry for the Handicapped to investigate their opinions about the need for education and training of dentists in the delivery of oral care to people with handicaps. Their educational experience was explored. Views on education and training were investigated in relation to timing, content and methods. Three hundred and sixty five questionnaires were sent and the total response rate was 67.4 per cent. There was a higher percentage of females than males and a higher percentage of 30 to 39 year old subjects in the sample. The data were analysed using the 'Survey Plus' program. A high proportion of respondents thought there was a need for education and training of dentists in the delivery of care to people with handicaps (70 per cent). Their views on training provided information on three main issues: the type of training course, and the content and methods of training or education. In-service training, observation of other dentists and continuing education courses were opportunities that people considered would have helped them. Although views varied, there was a notable desire for contact with experienced clinicians, particularly the observation of them carrying out treatment, the opportunity for participating in teaching methods, discussions and problem-solving aids. The involvement of carers and of people with handicaps themselves was suggested. Undergraduate and postgraduate education were both considered important, although postgraduate training was the more highly favoured. In relation to the content of training, behaviour management, communication skills and appropriate treatment planning were most commonly identified. This information will be useful for those wishing to establish courses.


Treatment accessibility for physically and mentally handicapped people--a review of the literature.

This paper presents a review of the literature concerning the access of physically and mentally handicapped people to dental care, and the attitudes of dentists towards them. It is particularly concerned with access for those who are housebound, or restricted to wheelchairs. Accessible dental care facilities and information about them may have been difficult to locate in the United Kingdom. This situation may improve in the near future as family health services authorities have data obtained from dentists registering with them under the new National Health Service contract, and general dental practice leaflets are required to provide information on wheelchair access. Transport systems may severely limit the ability of some handicapped people to travel to otherwise accessible surgeries. Professional and societal attitudes towards handicapped people are ambivalent. It has been shown that professional attitudes towards handicapped people, and willingness to treat them, increases with training in this field. At present, this training has a low priority in many dental schools.


The influence of terfenadine and ipratropium bromide alone and in combination on bradykinin-induced nasal symptoms and plasma protein leakage.

Nasal instillation of bradykinin elicits many of the characteristic features of rhinitis. To assess the relevance of histamine release from metachromatic cells and the activation of cholinergic pathways, we investigated the effects of terfenadine, a histamine H1-receptor antagonist, and ipratroprium bromide, a selective antimuscarinic agent, on bradykinin induced rhinorrhoea, nasal airways resistance (NAR), nasal pain and plasma protein leakage. Oral terfenadine (120 mg) or matched placebo and nasal ipratropium bromide (80 micrograms) or matched placebo were administered at 4 hr and 30 min respectively prior to bradykinin nasal challenge in two randomized, double-blind and cross-over studies on eight non-rhinitic subjects. Thus subjects received either double-placebo, oral terfenadine and nasal placebo, oral placebo and nasal ipratopium bromide or oral terfenadine and nasal ipratropium bromide, as pretreatment. Bradykinin challenge induced mean maximal increases of 57%, 59%, 77% and 72% in NAR on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratropium bromide pretreatment days respectively. These increments were not significantly different. Similarly rhinorrhoea and nasal pain induced by bradykinin nasal challenge were not significantly different on the four challenge days. Bradykinin nasal challenge caused a mean maximal increase in albumin levels in recovered nasal lavages of 11.5, 13.0, 12.2 and 12.3 times of baseline levels on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratroprium bromide pretreatment days respectively. Similarly total protein levels achieved a mean maximal increase of 8.0, 8.2, 7.9 and 8.8 times of baseline levels on these challenge days. The increments in both albumin and total protein did not significantly differ on the 4 challenge days.(ABSTRACT TRUNCATED AT 250 WORDS)


Oral care for the homebound and institutionalized.

Most patients who are homebound or in LTC facilities have multiple health problems that require the cooperation of many different types of providers. Dentists have a specific role in this process because they can improve the quality of life for the elderly by keeping them free of oral infection, restoring their dentition so they can enjoy eating, and restoring facial esthetics. It should be apparent that dental care for these patients is a complicated process. There are many considerations in prescribing the type of treatment needed by each patient. These include the patient's life span, medical history, drug history, mental status, mobility status, neuromuscular coordination, dental status, previous dental experience, dental expectations, and economic status. This information must be gathered by the dentist from the patient, the family, the nursing staff, and the patient's physician. Furthermore, the dentist also must assess the facilities and equipment available to carry out oral health care. Only after such considerations can a dental treatment plan evolve that is appropriate for the individual concerned. Dental care for one patient may be no treatment whatsoever, whereas a different patient in the same institution may require the most technologically sophisticated care that dentistry has to offer. Finally, the following circumstances should suggest that a homebound or institutionalized patient needs an urgent oral/dental evaluation: General Signs and Symptoms; Orofacial pain, Visible oral infection, Difficulty chewing food, Halitosis/dry burning mouth, Visible oral soft tissue lesions (white, red, or ulcerated). Tooth-related signs and symptoms; Visible dental decay, Loose or mobile teeth, Bleeding or sore gums. Denture-related Signs and Symptoms; Loose, ill-fitting, or worn dentures, Missing denture teeth, Home repairs attempted.


[Changes in left ventricular filling after acute increase of afterload in essential arterial hypertension with or without left ventricular hypertrophy].

It is debatable whether a direct causal link exists between left ventricular hypertrophy (LVH) and abnormal left ventricular filling (LVF) in arterial hypertension (AH). To assess if LVH is responsible for peculiar patterns of LVF, we examined 30 selected subjects, similar in age and body surface area, by Doppler echocardiography: 10 hypertensives (SBP: 158 +/- 15; DBP: 105 +/- 7 mmHg) with LVH (IM: 154 +/- 19 mg/m2) (Group 1); 10 hypertensives (SBP: 157 +/- 9; DBP: 101 +/- 5 mmHg) without LVH (IM: 105 +/- 17 mg/m2; Group 2); 10 normotensives without familiar history of AH (Group 3). LVF was analyzed in baseline conditions and during transient afterload increase, obtained by isometric exercise (handgrip, HG, for 5 min at 30% of maximal effort). At rest: 1) A wave peak velocity resulted significantly higher (p less than 0.01) in Group 1 (61 +/- 3 cm/s) versus Group 3 (52 +/- 7 cm/s), and E wave peak velocity was significantly lower in Group 1 (58 +/- 13 cm/s) versus Group 3 (74 +/- 10 cm/s); 2) Group 2 values (E wave: 66 +/- 12; A wave: 58 +/- 15 cm/s) were intermediate between those of groups 1 and 3, and with no significant differences; 3) E/A ratio resulted significantly lower both in Group 1 (1.04 +/- 0.2) and Group 2 (1.21 +/- 0.2) versus Group 3 (1.6 +/- 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)


[Giardiasis in dog and cat owners].

In subjects with positive giardiasis tests examinations of contacts were made not only in all members of the family but also in dogs and cats living with them in the same household. Attention was paid to the possible transmission of giardias. A total of 174 families were examined, i.e. 1140 subjects incl. 156 positive ones. Of 123 examined dogs 9 were positive and of 56 cats 8 were positive. Forty-three dog keepers were negative, of their 222 dogs 60 were positive. Although no association was proved between the infection of domestic animals and humans in the examined group, it is recommended to treat not only humans but also domestic animals.


[Use of the Streptotest for identification of enterococci and viridans-type streptococci].

The new identification system STREPTOtest (fy. Lachema, Brno) was evaluated. A total 118 well-known strains of genus Enterococcus, Streptococcus, Aerococcus, Stomatococcus and Gemella were tested. The STREPTOtest system rapidly and reliably distinguished genus Enterococcus from genus Streptococcus. This method identified correctly to the species level 65.9% of enterococci strains and 52.5% of streptococci strains. The STREPTOtest was used for identification of A. viridans and S. mucilaginosus and it was possible to separate these strains from similar ones. A new differentiation chart for identification of all 13 recently described enterococcal species was proposed.


[Review of new methods of investigating cellular immunity].

The objective of this review is to describe some recent methods which are used to examine the specific and non-specific cellular defense of the body. Greatest attention is devoted to methods which are not mentioned in the publication "Selected diagnostic methods in medical immunology" by J. Procházková (Prague, Avicenum 1986). The article summarizes data from the literature on recent examination methods of various parameters of cellular immunity such as detection of surface membrane antigens of immunocompetent cells, examination of cytotoxic activity, blastic transformation and activation of cells of the immune system.


[Vaccination against tick-borne encephalitis in the Central Slovakia Region using a Soviet vaccine].

During the period between 1986 and 1989 in the region 1311 people working in forestry were vaccinated against tick-borne encephalitis by the inactivated Soviet vaccine. Only some of the people had prevaccination examinations only in some reactogenity of the vaccine was investigated as well as the persistence of humoral antibodies one and two years after the basic vaccination. These examinations in some of the vaccinated subjects were made in autumn 1986 and spring 1987. After two doses of vaccine in the haemagglutination-inhibition test (HIT) the seroconversion was 77% (of 182 evaluated) with a geometric mean of 37.9. One year after the primary vaccination in 53% of the examined subjects the titre of humoral antibodies dropped to negative values. Two years after the primary vaccination in the HIT antibodies were detected in 44% of 57 examined subjects. None of the immunized subjects contracted tick-borne encephalitis.


[New findings on alpha-hemolytic strains of E. coli in urinary tract infections. II. Antigen structure, resistance, production of colicins and siderophores].

Alphahaemolytic uropathogenic strains of E. coli (UPEC) belong mostly into the serogroup 04, 06, 018 and 075. UPEC are resistant against antibacterial substances and against the bactericide action of serum. Properties which condition the virulence of these strains are also colicin and siderophore production.


[An explosive familial epidemic of viral hepatitis B with a horizontal transmission].

The authors describe the course of an explosive epidemic of viral hepatitis B (VHB) where all members of a seven-member family contracted the disease. The probable source of infection was an infant with a history of anicteric VHB with transition into chronicity and with HBs and HBe antigenaemia. Four members of the family contracted the disease between the 126th and 172nd day after his return from hospital to the family and another two members of the family contracted the disease three months later. Generally accepted risk factors for transmission of VHB could be ruled out. Saliva is suspected as a transfer factor of the disease. Five children had the anicteric form of VHB with an atypical but protracted course, in two with probable development of a chronic character of the disease. Adult patients had the icteric form of the disease. All cases were diagnosed by biochemical examination and confirmed by a positive finding of HBsAg and/or a positive finding of anti HBs antibodies.


[Prevalence of hantavirus infection in small mammals in the South Moravian Region].

In 1987 to 1990 in the South Moravian region 1094 lungs of small terrestrial mammals were examined for hantavirus antigen and sera of 525 rodents and 93 hares for antibodies against these viruses. In the majority the materials were not from the same individual. Lungs were examined by the ELISA method, antibodies were assessed by the indirect immunofluorescence reaction. An antigen resembling the western subtype (Puumala) was found in 65 animals (5.9%) of two rodent species (Microtus arvalis--63 times and Apodemus flavicollis--twice) in 20 localities. Antibodies against this subtype were detected in 25 examined individuals (4.0%) of four species (Microtus arvalis, Apodemus flavicollis, Pitymys subterraneus and Lepus europaeus) from eight localities. A marked predominance of positive findings was obtained from Microtus arvalis which under conditions of the South Moravian region can be considered the main host of hantaviruses of the western subtype. Only in one specimen of Clethrionomys glareolus from Hrbov antibodies against the eastern subtype were detected (Hantaan). Hantaviruses form in Southern Moravia natural foci of the avector type, in particular in perennial fodder crops, most frequently with a mesophil character of the site. The foci were found most frequently at sites of assumed borderlines of natural meadow forests of the Alno-Padion type and woods of the Carpinion betuli, Quercion robori-petreae and Fagion silvaticae type.


Quantitative analysis of factors contributing to handicap and distress in vertiginous patients: a questionnaire study.

Statements encapsulating common beliefs, behaviour and difficulties associated with vertigo, derived from in-depth interviews, were used to construct a Vertigo Handicap Questionnaire (VHQ) which was completed by 84 patients referred for vestibular testing. Factor analysis identified four principal components of handicap in addition to 'Anxiety and Depression', (which was isolated prior to analysis): 'Restriction of Activities', both physical and social; concern that vertigo would adversely affect social relationships ('Social Anxieties'); 'Fear of Vertigo', both the attacks themselves and their possible significance; and 'Severity of Attacks' which was multiplied with frequency of attacks to give a measure of reported physical disability. Multiple regression revealed that Severity x Frequency of attacks contributed to patient distress only indirectly, through its influence on the mediating psychological and behavioural variables. Significant patient benefit may therefore result from counselling or behavioural therapy, whether or not the vertigo itself can be controlled.


Acute subendocardial infarction with diffuse intense Tc-99m PYP uptake and minimal Tl-201 abnormality.

Tc-99m PYP scintigraphy performed on a patient with severe anterior chest pain showed diffuse intense uptake with central decreased activity corresponding to the left ventricular cavity. Tl-201 myocardial perfusion scintigraphy at rest revealed a minimal perfusion abnormality with decreased apical uptake in the lateral view. Because of these findings, diffuse subendocardial infarction was suggested.


[The association of amlodipine with isosorbide-5-mononitrate in the treatment of ischemic-hypertensive cardiopathy].

Every form of therapy must always aim at obtaining maximum benefit with minimum use of drugs; also for the purpose of ensuring maximum patient compliance. With this end in mind, 21 patients with ischemic heart disease and arterial hypertension were divided into three groups of seven subjects each and submitted to different drug treatments with single daily doses: group 1 received isosorbide-5-mononitrate (60 mg), group 2 amlodipine (10 mg), and group 3 a combination of both drugs at the same dosage, for four weeks. Statistical analysis showed blood pressure values to have been significantly reduced in subjects receiving amlodipine both alone and in combination (p less than 0.05) while no significant variation was observed (p = n.s.) in those treated with isosorbide-5-mononitrate only. A significant reduction of diastolic blood pressure (p less than 0.05) occurred only in patients talking the combination. No significant changes of heart rate (p = n.s.) were observed in any of the groups. Tests at the cycling ergometer revealed increased in any of the groups. Tests at the cycling ergometer revealed increased maximal effort tolerance for all three groups but the increase was more marked in patients taking the combination (who from 130 +/- 10 Watt increased to 160 +/- 20 Watt). This was confirmed also by the reduced consumption of trinitrine capsules which diminished in groups 1 and 2 from an average of 5/week to 2/week but was completely abolished in group 3. Also ST depression was significantly reduced (p less than 0.05) only in this latter group.(ABSTRACT TRUNCATED AT 250 WORDS)


Contact allergy to tioconazole.

In 15 months, we detected allergic patch test reactions to tioconazole in 14 patients. 9 of the 14 patients were allergic to additional imidazole derivatives used as antifungal agents. The positive patch test reactions to tioconazole may have been caused either by simultaneous sensitization or more probably by cross-reactivity between the various commercially used imidazole derivatives with a similar chemical structure. The abundant use of tioconazole in concentrated (up to 28%) topical formulations in Finland could be the major cause of the apparent increase in allergic reactions.


Assignment of the human cyclin D3 gene (CCND3) to chromosome 6p----q13.

The PRAD1/cyclin D1 gene (CCND1), a member of the D-type cyclin gene family, has been implicated as a protooncogene in parathyroid, lymphoid, and mammary tumors. We cloned and mapped another member of this family, the human cyclin D3 gene (CCND3), to chromosome 6p----q13 using human x rodent hybrids. This assignment raises the hypothesis that cyclin D3 may be involved in the pathogenesis of human neoplasms with abnormalities of chromosome 6.


The relative effects of maternal and child problems on the quality of attachment: a meta-analysis of attachment in clinical samples.

In this meta-analysis of 34 clinical studies on attachment the hypothesis is tested that maternal problems such as mental illness lead to more deviating attachment classification distributions than child problems such as deafness. A correspondence analysis on 21 North American studies with normal subjects produced a baseline against which the clinical samples could be evaluated. Separate analyses were carried out on studies containing the traditional A, B, C classifications and on studies that also included the recently discovered D or A/C category. Results show that groups with a primary identification of maternal problems show attachment classification distributions highly divergent from the normal distributions, whereas groups with a primary identification of child problems show distributions that are similar to the distributions of normal samples. The introduction of the D or A/C classifications (about 15% in normal samples) reveals an overrepresentation of D or A/C in the child problem groups, but the resulting distribution still is much closer to the normal distributions compared to the samples with maternal problems. In clinical samples, the mother appears to play a more important role than the child in shaping the quality of the infant-mother attachment relationship.


[Laparoscopic side-to-side gastrojejunostomy].

Development of laparoscopic stapling devices and growing experience with the new method made resective and reconstructive operations on the digestive system accessible to laparoscopy. After extensively testing the method on pigs, we now report on laparoscopic gastro-jejunostomies performed in two patients for gastric stenosis due to inoperable carcinoma of the pancreas. The technique is described. It requires expensive instruments and a very skilled surgeon. While being a safe procedure in the hands of a well-trained surgeon, it presents a high degree of difficulty. Therefore, in order to avoid complications, it should not be advised for a large scale application before results of a greater number of cases can be presented.


[Effect of highly active atrial natriuretic peptide and changes of superoxide dismutase level in pregnancy induced hypertension].

In this paper, patients with severe pregnancy induced hypertension (PIH) were treated with a highly active atrial natriuretic peptide (haANP). The results indicated that the effect of haANP in decreasing blood pressure (BP), clearing proteinuria and detumescence was marked. Serum hSOD-1 concentrations after haANP infusion decreased significantly (P less than 0.01). This may be related to the amelioration of the disease. Serum hSOD-1 concentrations in normal pregnancy and mild, moderate PIH were higher than in the non-pregnant. Serum hSOD-1 concentration in severe PIH was highest. These findings suggested the presence of a defence mechanism in the body against oxidative damage on tissues. The pathogenesis of PIH may be associated with the defence effect of the hSOD-1, and defective free radicals. The initial results suggest that ANP may be related to hSOD-1 in normal pregnancy as well as in PIH.


[221 cases of laparoscopic laser therapy].

Laparoscopic laser therapy, using a Nd:YAG laser and an Olympus laparoscope, was performed in 221 cases. 0.5% dicaine spray was used intraperitoneally. The types of operations performed were tubal sterilization in 110 cases, vaporization of endometriotic lesions in 76 cases, lysis of pelvic adhesions in 13 cases, salpingostomy in 11 cases, salpingostomy for tubal pregnancy in 10 cases, and fenestration of cyst of Morgagni in one, the rate of success was 98.2% in tubal/sterilization. In 71 cases of endometriosis the pregnancy rate was 32.7% for R-AFS stage I-II, and 25.0% for stage III-IV cases. The advantages and techniques of the laparoscopic laser therapy were discussed.


Response to HBV vaccination in patients with severe liver disease. Absence of an HLA effect.

HLA antigen profiles have been used to identify individuals who are likely not to respond to HBV vaccination. The majority of these reports have included either normal individuals or individuals with severe abnormalities of their immune system. The present investigation assessed the rate of HBV vaccination seroconversion in 132 individuals with chronic advanced liver disease who were referred for possible liver transplantation. Each was vaccinated using a serum-derived vaccine administered intramuscularly at three consecutive monthly clinic visits. As part of their transplant evaluation, each subject also underwent HLA typing for class I and class II antigens. Of the 132 subjects vaccinated, only 47% seroconverted and became HBsAb positive. There was no difference between types of liver disease. As expected, individuals older than 55 years of age responded less well than those younger than this cutoff age. No difference between seroconverters and nonresponders was evident for gender or any individual or combination of HLA antigens. In conclusion, individuals with advanced chronic liver disease seroconvert less often in response to HBV vaccination than do normal individuals. Moreover, unlike normals and the experience with other disease groups, no difference in conversion rates was evident for gender. Similarly, no difference in seroconversion rates was evident for the two major pathophysiologic types of chronic liver disease. Age greater than 55 years was associated with a reduced rate of seroconversion.


Is combination sulfonylurea and insulin therapy useful in NIDDM patients? A metaanalysis.

To assess the efficacy of combination therapy with insulin and sulfonylurea in the treatment of NIDDM. Studies published between January 1966 and January 1991 were identified through a computerized Medline search and by hand searching the bibliographies of identified articles. We identified 17 eligible randomized, controlled trials of combination therapy in NIDDM. These trials had a minimum duration of 8 wk and at least one of three outcome measures (fasting glucose, HbA1, or C-peptide) with SD or SE of the mean reported to do metaanalysis. With standardized forms, three independent reviews abstracted measures of study quality and specific descriptive information about population, intervention, and outcome measurements. We calculated effect size and weighted mean changes of the three outcome measures for control and treatment groups. In the treatment group, the fasting plasma glucose decreased from a mean of 11.4 mM (206 mg/dl) at baseline to a mean of 9.16 mM (165 mg/dl) posttreatment, whereas the control group decreased from (11.3 to 10.8 mM) (204 to 194 mg/dl) (effect size 0.39, P less than 0.0001). For HbA1, the treatment group decreased from a baseline of 11.0 to 10.2% compared to 11.0 and 11.2% in the control group (effect size 0.43, P less than 0.0001). For fasting C-peptide, the treatment group increased from 0.49 to 0.58 nM (1.45 to 1.75 ng/ml) compared with 0.47 and 0.43 (1.42 and 1.30) for the control group (effect size 0.26, P less than 0.017). Combined insulin-sulfonylurea therapy leads to modest improvement in glycemic control compared with insulin therapy alone. With combined therapy, lower insulin doses may be used to achieve similar control. Obese patients with higher fasting C-peptides may be more likely to respond than others.


Lipoprotein(a) in diabetic patients with and without chronic renal failure.

To examine the distribution of Lp(a) plasma levels in patients with IDDM and NIDDM, and in nondiabetic and IDDM patients with chronic renal failure. Cross-sectional study of Lp(a) plasma levels in a population of diabetic patients with stable metabolic control, with simultaneous determination of plasma lipids, fasting plasma glucose, and HbA1. Thirty-six patients with IDDM, 90 with NIDDM, and 41 with chronic renal failure (20 IDDM, 21 nondiabetic) were compared with 78 control subjects. Lp(a) plasma levels were significantly higher in IDDM and NIDDM patients, as well as in nondiabetic and IDDM patients with chronic renal failure compared with control subjects. No correlation was observed between Lp(a) and lipid plasma levels, fasting plasma glucose, and HbA1. Lp(a) may contribute to the increased prevalence of atherosclerotic disease in diabetic patients and patients with chronic renal failure, especially in IDDM patients whose lipoprotein pattern was not different from that of the control group.


[Latex proteins as the trigger of respiratory and systemic allergies].

56 patients (52 members of the hospital's staff, four with other employment) who had hypersensitivity reactions to latex articles and developed an immediate-type response to latex extract with the skin-prick test were studied. Specific IgE antibodies were present in the enzyme-allergo-sorbent test of 50 of the subjects. Latex-containing surgical and household gloves were the main cause of allergies. Patients with isolated contact urticaria (n = 8) had a tendency towards lower antibody concentrations than those with additional respiratory and/or systemic symptoms (n = 48). Occupation-related provocation tests triggered rhinitis in 19, conjunctivitis in ten, and bronchial obstruction in six. The main allergen was found to be a protein with a relative molecular mass of 58,000, originating from the latex milk and passing from the latex glove into the glove powder. In the course of usual activities considerable allergen inhalation can occur. Even small amounts (e.g. 400 ng/ml) can precipitate significant allergic reactions. The results show that the main latex allergen, a glycine-rich protein molecule, can cause cutaneous, inhalant and systemic hypersensitivity reactions.


Clinical studies on isradipine in the management of adult hypertensive patients at Moi University Teaching Hospital, Eldoret, Kenya.

In a 16 weeks open label therapeutic trial, studies were performed on isradipine (Lomir) to evaluate its haematological and biochemical safety and hypotensive capacity in the management of adult black hypertensive patients. The mean sitting diastolic blood pressure decreased from 105.5 +/- 9.66 mm hg at the end of the washout period to 92.1 +/- 7.59 mm hg at the end of the study, p less than 0.0001; while the mean standing diastolic blood pressure was 108.0 +/- 7.10 mm hg and 93.9 +/- 8.4 mm hg at the end of the washout phase and at the completion of the therapy respectively, p less than 0.0001. The corresponding mean sitting systolic blood pressures were 155.4 +/- 9.91 mm hg and 140.6 +/- 9.47 mm hg, p less than 0.001 while the corresponding mean standing systolic blood pressures were 156.6 +/- 12.50 mm hg and 142.6 +/- 9.15 mm hg, p less than 0.001. There were negligible changes in the mean heart rate; from 79.5 +/- 9.23 beats per minute (bpm) at the end of the placebo phase to 78.2 +/- 9.15 bpm at the end of the study in the sitting position, p greater than 0.1. The corresponding mean standing values of heart rate were 82.5 +/- 11.33 and 78.6 +/- 8.76, p greater than 0.5. The haematological, biochemical and electrocardiographic parameters remained within normal limits during the study. Side effects were mild, transitory, improved with therapy and consisted of dizziness, palpitations, headache, nocturia, tiredness and fainting attacks. The study achieved 96% good-to-excellent results with respect to both efficacy and tolerability. Isradipine (Lomir) is therefore an efficacious and safe antihypertensive agent in the management of black adult patients with mild to moderate primary arterial hypertension when administered in the dose of upto 2.5 mg twice daily alone or in combination with a beta-blocker.


Acceptable workloads for three common mining materials.

A series of psychophysical lifting studies was conducted to establish maximum acceptable weights of lift (MAWL) for three supply items commonly handled in underground coal mines (rock dust bags, ventilation stopping blocks, and crib blocks). Each study utilized 12 subjects, all of whom had considerable experience working in underground coal mines. Effects of lifting in four postures (standing, stooping under a 1.5 m ceiling, stooping under a 1.2 m ceiling, and kneeling) were investigated together with four lifting conditions (combinations of lifting symmetry and lifting height). The frequency of lifting was set at four per min, and the task duration was 15 min. Posture significantly affected the MAWL for the rock dust bag (standing MAWL was 7% greater than restricted postures and kneeling MAWL was 6.4% less than stopped); however, posture interacted with lifting conditions for both of the other materials. Physiological costs were found to be significantly greater in the stooped postures compared with kneeling for all materials. Other contrasts (standing versus restricted postures, stooping under 1.5 m ceiling versus stopping under 1.2 m ceiling) did not exhibit significantly different levels of energy expenditure. Energy expenditure was significantly affected by vertical lifting height; however, the plane of lifting had little influence on metabolic cost. Recommended acceptable workloads for the three materials are 20.0 kg for the rock dust bag, 16.5 kg for the ventilation stopping block, and 14.7 kg for the crib block. These results suggest that miners are often required to lift supplies that are substantially heavier than psychophysically acceptable lifting limits.


An ergonomic evaluation of nursing assistants' job in a nursing home.

Thirty-eight nursing assistants (NAs) in a nursing home ranked and rated 16 different patient handling tasks for perceived stresses to the low back. The nursing assistants were observed for 79 4 h shifts and were videotaped for 14 4 h shifts to describe a typical workday and to determine the number of patient-handling tasks performed per shift, the use of assistive devices, and biomechanical stresses to the low back. In addition, data were collected on nursing assistants' and patients' characteristics. The top eight ranked tasks included transferring patient from toilet to wheelchair (WC), WC to toilet, WC to bed, bed to WC, bathtub to WC, chairlift to WC, weighing patients and lifting patients up in bed. The mean ratings of perceived exertion for these tasks were between 'somewhat hard' and 'hard'. The estimated compressive force on L5/S1 disc for the 50th percentile patient weight ranged from 3.7 to 4.9 KN. Nursing assistants worked in teams of two and performed 24 patient transfers per 8 h shift by manually lifting and carrying patients. Assistive devices (a hydraulic lift and gait belt) were used less than 2% of the time. Patient safety and comfort, lack of accessibility, physical stresses associated with the devices, lack of skill, increased transfer time, and lack of staffing were some of the reasons for not using these assistive devices. Environmental barriers (such as confined workplaces, an uneven floor surface, lack of adjustability of beds, stationary railings around the toilet, etc.) made the job more difficult. Nursing assistants had a high prevalence of low-back pain and 51% of nursing assistants visited a health care provider in the last three years for work related low-back pain.