[Evaluation of the timing principle with vecuronium].

We evaluated the usefulness of the timing principle with vecuronium in 60 patients who underwent elective surgery, and divided into two groups according to the dose of vecuronium (0.15 and 0.2 mg.kg-1). First, we studied the interval between vecuronium and thiopental administration in 40 patients. The time after vecuronium administration to onset of clinical muscle weakness was 57.6 +/- 7.8 sec in 0.15 mg.kg-1, and 42.2 +/- 2.2 sec in 0.2 mg.kg-1 group. Then, we made and examined the protocol of the timing principle for the rapid tracheal intubation. Induction of anesthesia with 4-5 mg.kg-1 thiopental was done 40 sec after 0.15 mg.kg-1 in 10 patients, and 30 sec after 0.2 mg.kg-1 vecuronium administration in 10 patients. Intubating conditions were almost excellent 70 sec after thiopental administration. In our study, there were no patients who experienced discomfort during induction. We conclude that the timing principle with vecuronium is useful for rapid-sequence tracheal intubation.


[Early synovectomy in the treatment of juvenile rheumatoid arthritis].

Authors report on the results of 15 synovectomies of the knee for iligoarticular juvenile rheumatoid arthritis. The operation was performed in every case in the early stage before the development of the radiological destruction. Excellent and good results were obtained in 11 cases; in 4 cases the operation was unsuccessful. It is stated that there is good chance to prevent destruction of the knee with juvenile rheumatic arthritis with an early synocvectomy. The operation is suggested after 6 years of age. The key of the good result is the early intensive mobilization of the joint.


[Abdominal injuries in polytraumatised patients].

Authors have observed in 1978-1984 in 87 of 214 polytrauma cases injuries of the abdominal organs. The data concerning children in whom the high ratio of injuries of the abdominal organs and the low mortality are conspicuous are shown separately. The necessity of urgent diagnosis to which especially the abdominal irrigation has given great help is stressed. After a review of the literature and a control of their own material the problem is considered as actual, as in polytraumas the abdominal injuries are frequent, the valuation of the abdomen in the patient, generally in shock or unconscious is problematic, the many times simultaneous therapy of the abdominal and joined injuries is difficult, the mortality high.


[Results of sonographic hip examination of infants in a risk group].

During sonographic examination of 770 newborns and infants the diagnostic value and the possibility of valuation of singular risk factors were investigated. According our data an acetabular dysplasia, requiring treatment can be found most frequently in the background of a limitation of abduction motion. Pathologic alterations may be found less frequently in groups with familiar anamnesis and with breech presentation. It could be stated that the aspecific click is a clinical symptom of significance and cannot be neglected whereas we could not prove connections between asymmetry of the folds and the sonographic data. Our results prove that the anamnesis and the clinical symptoms alone do not make a perfect recognition of the dysplasia possible; in consequence it is suggested that sonography should be used as a screening.


[Ultrasonic examination of soft tissue injuries in the shoulder region].

Authors call attention with the demonstration of pictures of a few cases of their own to the significance of the ultrasound examination in cases of shoulder injuries. They stress that beside the demonstration of rotator cuff injuries the examination of the surrounding muscles and the labrum glenoidale should not be forgotten either. The modernization of the ultrasound devices, the improvement of the methods of examination and the obtaining of the necessary practice ensure a more and more important place to echography in the diagnosis of traumas of the motion organs.


[Treatment of idiopathic femur head necrosis by implantation of a preserved bone graft. Critical evaluation of the method].

Author reports on the result of treatment in 22 patients with idiopathic femoral head necrosis. Altogether 25 hips were treated with insertion of conserved bone graft. Improvement occurred in only about 1/4 of the operated hips, the other hips deteriorated both clinically and radiologically. The author thinks, reviewing the literature, that the cause of the partly failure was the inadequate selection of patients and the insufficiency of the method. The possibilities of further progression are outlined.


[Management of tibial fractures with Ender nailing].

Authors have performed in 1984-1986 46 Ender nailings based on definite indications as treatment of lower leg fractures in the Department of Traumatology, Arpád Hospital, Ujpest. In their clinical study they stress the criteria of the choice of this method, underline the advantages and disadvantages of the stabilization with elastic nails. This treatment used especially for fractures of the distal third lightens the care, the mobilization, shortens the stay in the hospital, diminishes the number of the septic complications. In many cases authors recommend it as a good alternative method, based on own experiences and results, to surgeons forced to accept a compromise.


[Emergency treatment of severe burns in daily practice].

The paper examines the initial treatment of the severely burned patient to be transferred. It is stated that the aspirations for a uniform expert treatment have not yet brought a complete success. The suggestions concerning this problem, described in the Methodological Letter "Treatment of Thermic Injuries" issued by the Nat. Institute of Traumatology are discussed and repeated.


[Bicycle accidents].

Authors analyse the 1684 bicycle accidents, observed in the county Vas in one year, compared with the international data. It is underlined that no sufficient attention is given to the bicycle accidents, reaching 6 per cents of all traumas, and the increase of which can be still expected, and to the prophylaxis of these accidents. Especially endangered were found the little children transported on bicycles, those aged 11-14 years and the drunken drivers. Prophylactic measures are suggested.


[Management of lower leg fractures by external fixators and thermoplastic braces. Preliminary report].

Authors describe their new combined method for treatment of lower leg fractures. To this a new type fixator was developed which makes dynamization also possible. The other novelty in this country is the use of functional external fixing brace. In all of the 38 patients they had succeeded to obtain healing. No complication was found until now.


[Chondromatosis of the hip joint].

The case of a 42 years old man is described who had complaints in his left hip since 9 years for synovial chondromatosis. During the operation 38 cartilaginous free bi dies were removed and at the same time synovectomy was also performed. The chondroma not observed and not removed at the exposure was spontaneously resorbed during the follow-up time. Authors think the case interesting because during the last 30 years no similar description was found in the Hungarian literature.


[Possibilities of surgical management of fractures of the scapular corpus].

Authors report on the possibilities of the operative treatment of the corpus scapulae. In chosen cases--young patients, isolated occurrence, great dislocation--they have performed the plate osteosynthesis of the corpus fractures. The frequency of the occurrence, the classification of fractures, the possibilities of the operative technique, the indication of the operations, the postoperative therapy are mentioned and their cases are described.


[The role of Gardner's classification in the detection of dislocation in femoral neck fractures].

As the literary data are contradictory, authors examined in 489 operated femoral neck fractures the significance of Garden's classification. Based on their material it was found that this classification gives help in the judgement of the single fractures and in the choice of the adequate treatment. For a more exact assessment however they think the consideration of the lateral Roentgenograms also necessary.


[Bone transplantation methods].

Author sums on the basis of the literature of this country and of the international literature the more frequently used methods of bone substitution, their mechanical and biological characteristics. On the basis of the practice of their institute and of the international publications it can be stated that beside the usual transplantation of preserved bone the always increasing clinical claim makes the introduction and the knowledge of other methods also necessary. The advantages and disadvantages of the bone grafts of different types are detailed. It is stated that none of the implantates of different characteristics fulfils perfectly the ideal mechanical and biological requirements. To obtain the possibly best result it is recommended to choose, and on individual indication, the bone substitution method that will fulfil in the given case the requirements desired.


Effect of sialectomy on the superior cervical ganglion sympathetic neurons in young adult and aged mice.

The dependence of superior cervical ganglion (SCG) adrenergic neurons on their target organ submandibular salivary gland containing high concentrations of nerve growth factor was studied in adult and aged male mice. The submandibular salivary glands were removed (sialectomy) either uni- or bilaterally, and the SCG were studied by fluorescence microscopy and histochemically. Catecholamine fluorescence and tyrosine hydroxylase immunoreactivity decreased after sialectomy, suggesting reduced noradrenaline production. Neuronal density was lower in the aged controls than in the young controls. In both age groups, sialectomy reduced the density of catecholamine-producing neurons. In the mouse SCG, there was remarkable heterogeneity in the size of neuronal somata. In aged control mice there was a greater number of large-size neurons than in young adult control mice. Six weeks postoperatively, no large catecholamine-producing neurons could be observed in the ganglia. Yellow autofluorescent lipopigments accumulated with age in the adrenergic neurons. Sialectomy increased the accumulation of lipopigments in both young and aged neurons. Sialectomy resulted in (a) reduced catecholamine fluorescence, (b) reduced tyrosine hydroxylase immunoreactivity, (c) reduced number of catecholamine neurons, (d) increased autofluorescent lipopigment. Ageing resulted in (a) reduced number of neurons, (b) increased ratio of large to small neurons, (c) increased autofluorescent lipopigment. Alterations after sialectomy were more detrimental in the aged ganglia than in the young adult ganglia. The discontinuation of the retrograde supply of nerve growth factor may contribute to these alterations.


Biogenic amines in the guinea pig endocrine pancreas.

Pancreata of guinea-pigs were investigated for the presence and cellular distribution of biogenic amines. Out of the established endocrine cell types only insulin (B-) cells contained immunoreactivity for serotonin and noradrenaline. However, the B-cells' content of both amines was quite variable. Serotonin was also confined to enterochromaffin (EC-) cells. No immunoreactivity for dopamine or histamine was present in any islet cell. Treatment of guinea-pigs with Ro-4-4602 led to a marked decrease of serotonin and noradrenaline in pancreatic endocrine cells. The present findings suggest that serotonin and noradrenaline are involved in the function of the endocrine pancreas, particularly of islet B-cells.


Detection of genes coding for listeriolysin and Listeria monocytogenes antigen A (ImaA) in Listeria spp. by the polymerase chain reaction.

Two pairs of synthetic oligonucleotide primers were used in a polymerase chain reaction (PCR) protocol to detect targeted sequences in genes coding for listeriolysin O and Listeria monocytogenes antigen A (ImaA). Strains of Listeria spp. used in this study were isolated from clinical specimens, contaminated foods, and environmental sources. Primers were targeted to internal regions of the genes coding for listeriolysin (hlyA) and Listeria antigen (ImaA) and amplification fragments were detected after the PCR by agarose gel electrophoresis. PCR was performed using nucleic acids extracted from a collection of 74 strains of Listeria spp. including 18 reference strains, 41 L. monocytogenes, nine L. innocua, five L. seeligeri and one L. ivanovii, encompassing representative sources, serovars, and enzyme electrophoretic types. Although the listeriolysin gene was found exclusively in L. monocytogenes, some strains of serovar 4c were negative. Simultaneous presence of both genes was restricted to L. monocytogenes strains of serovars 1/2, 3, and 4. The ImaA gene was identified in five of 10 L. innocua strains and one L. ivanovii isolated from pork. Strains of L. seeligeri, L. welshimeri, and L. grayi were negative for both genes. The detection limits in the PCR were found to be 10 pg of nucleic acids for the hlyA gene and 1 pg for the ImaA gene.


Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation.

Scrapie and related animal and human disorders are neurodegenerative diseases characterized by the formation of a modified, partly proteinase-resistant protein (PrP) of the host, which tends to aggregate as amyloid fibrils and accumulate in the brain of infected individuals. There is a general consensus that the pathological form of PrP (PrPSc) is essential for the clinical appearance of the disease, but whether it is part of the scrapie agent or a by-product of viral infection is still controversial. Here we report that treatment of scrapie-infected hamsters with amphotericin B delays the accumulation in the brain of the proteinase-resistant portion of PrPSc by about 30 days without affecting scrapie replication. The consequence is that hamsters treated with amphotericin B developed clinical signs of disease later than infected controls. We argue that the proteinase-resistant portion of PrPSc is necessary for the development of the disease but that it is unlikely to be essential for scrapie replication.


Homeodomain-independent activity of the fushi tarazu polypeptide in Drosophila embryos.

The Drosophila segmentation gene fushi tarazu (ftz) encodes a homeodomain-containing protein, ftz, that can act as a DNA-binding activator of transcription. In the developing embryo, ftz is expressed in seven stripes which correspond to the even-numbered parasegments. These parasegments are missing in ftz- embryos. When ftz is expressed throughout blastoderm embryos under the control of a heat-shock promoter, the odd-numbered parasegments are lost. This 'anti-ftz' phenotype has been attributed to autoactivation of the endogenous ftz gene by the ectopically expressed protein. Here we show that the same phenotype is induced by ectopic expression of a ftz polypeptide containing a deletion in the homeodomain. Thus, ftz can alter gene expression without binding directly to DNA.


Bipotential precursors of B cells and macrophages in murine fetal liver.

LYMPHOCYTES (B and T cells) derive continuously from the same multipotential stem cells that produce myeloid cells, including erythrocytes, granulocytes and macrophages. Tri- and bipotential myeloid intermediates between the multipotential stem cells and later unipotential cells have been identified using clonal methods in culture. Although similar methods have detected committed pre-B cells in mouse fetal liver, earlier progenitors with additional non-B lineage options have not been demonstrated in normal tissues. We report the characterization and purification of fetal liver cells that generate clones containing both macrophages and B cells, identified biochemically and morphologically. The common origin of the two cell types was shown by culture of single precursor cells. Their dual potential and unrearranged immunoglobulin loci place the precursors before exclusive B-lineage commitment in the haematopoietic hierarchy. The availability of such cells in purified form will allow direct study of lineage choice in cells having both lymphoid and non-lymphoid options.


The jejunal secretory response to Escherichia coli heat-stable enterotoxin is prolonged in malnourished rats.

Undernutrition in human infants is associated with more prolonged episodes of diarrheal disease. Therefore, we tested the hypothesis that malnutrition prolongs the duration of Escherichia coli heat-stable enterotoxin-induced rat jejunal secretion. At weaning, rats were separated into two groups: malnourished rats were fed 50% of the previous day's intake of the fully fed control group. After approximately 2 wk of pair feeding, when malnourished rats weighed less than or equal to 60% of the full fed control group, we measured the secretory response to heat-stable enterotoxin in ligated jejunal loops. Toxin-induced secretion was equal in both groups until 30 min incubation time, after which net secretion continued to increase in the malnourished group but decreased in the fully fed group. Jejunal brush border membranes prepared from malnourished and fully fed rats demonstrated similar heat-stable enterotoxin receptor density, avidity of binding and guanyl cyclase activation. In both groups, radiolabeled toxin injected into in situ jejunal loops was converted into an altered radioligand unable to bind to brush border membranes. However, in malnourished rats, there was both increased appearance of two additional radioligands that still retained their ability to bind to brush border membranes and persistence of biologically active unlabeled toxin as measured in the suckling mouse bioassay. Our studies demonstrate that reduced or delayed inactivation of heat-stable enterotoxin, with continued presence of active toxin species, may contribute to prolonged secretion in the jejunum of malnourished rats.


Non-phenotypic selection of N-methyl-N-nitrosourea-induced mutations in human cells.

The distribution of mutations in a particular gene as detected by a selective mutation assay could be affected by the structural properties of the target protein. To investigate this, we have analysed N-methyl-N-nitrosourea (MNU)-induced mutations in two restriction recognition sequences of a target gene for mutation analysis and compared these data with what previously observed in a phenotypic mutation assay. DNA base changes in the Ncil and EcoRV sites of the gpt gene maintained in human cells by a shuttle vector system were measured by restriction fragment length polymorphism/polymerase chain reaction (RFLP/PCR) technique. After MNU-treatment of human cells, mutations were detected in the Ncil recognition sequence but not in the EcoRV site. DNA sequencing analysis revealed that all Ncil-resistant mutations were GC to AT transitions located over four bases of the Ncil recognition sequence. Only one of these mutations drastically affected the functionality of the GPT protein. The Ncil-resistant mutations were randomly distributed in both DNA strands of the gpt gene and were preferentially targeted at guanine residues flanked 5' by a guanine. Our results indicate that the structure of the GPT protein is the main contributor to the strand-specificity of MNU-induced mutations previously reported by using a phenotypic mutation assay. The potential use of the RFLP/PCR technique as a general tool for mutation detection is also discussed.


Effect of typical antipsychotic medications and clozapine on smooth pursuit performance in patients with schizophrenia.

The effect of typical neuroleptic drugs or clozapine on smooth pursuit eye movements was tested in 13 patients with schizophrenia or schizoaffective disorder with a repeated measures design. Nineteen normal control subjects were also studied. Compared with controls, patients in the unmedicated state had low smooth pursuit gain, had a higher rate of corrective catch-up saccades, and tended to spend less time engaged in the tracking task. The patients did not significantly differ from controls on catch-up saccade amplitude, square wave jerk rate, or anticipatory saccade rate. Medication with clozapine, but not typical neuroleptics, was associated with an increase in median catch-up saccade amplitude. Number of days on clozapine and clozapine dose both correlated significantly with a worsening of oculomotor performance. No effect of medication with typical neuroleptics was found, although there was some evidence suggesting that such an affect may occur after more prolonged treatment.


Treatment of extrapyramidal side effects with terguride.

Terguride, a partial dopamine agonist, was administered in a 4-week open clinical trial to 17 schizophrenic patients suffering from extrapyramidal side effects of neuroleptic treatment. The neuroleptic dosage was kept constant. The mean final daily dose of terguride reached 3.4 mg (SD = 2.0). Fourteen patients completed the trial. Total scores on the Rating Scale for Extrapyramidal Side Effects and the Brief Psychiatric Rating Scale showed a significant improvement of 69% and 40%, respectively. There was also a significant improvement in all BPRS factor scores.


Enzymuria and tubular proteinuria in diabetic rats: a 12-week follow-up study.

Various biochemical parameters of renal tubular function were examined for a period of up to 12 weeks in rats rendered diabetic by an i.v. injection of streptozotocin. Except for a statistically significant decrease in the urinary excretion of gamma-glutamyl-transpeptidase to 64% of control values, the urinary excretion of beta-N-acetyl-D-glucosaminidase, beta-galactosidase, alanine aminopeptidase, and lactate dehydrogenase significantly increases in diabetic rats to between 154% and 712% of control values. This increased enzymuria is not correlated to the marked polyuria induced by diabetes (r between 0.14 and 0.35, not significant). Enzymuria is also accompanied by a 10-fold increase in the urinary excretion of the low molecular weight protein beta 2-microglobulin while the excretion of albumin is not significantly modified, indicating impairment of tubular reabsorption in diabetic animals. Clearance studies reveal that the clearance of both beta 2-microglobulin and infused egg-white lysozyme are also increased. Finally the histopathologic examination of paraffin sections of the kidney show hydropic degenerescence and pycnosis of the tubular cells. It is concluded that early-stage diabetes results in tubular impairment and that the streptozotocin-rat model appears well suited to the study of these early signs of renal dysfunction.


Leukocyte adhesion deficiency: clinical and postmortem observations.

The clinical and autopsy findings in a patient with the severe form of leukocyte adhesion deficiency are presented. An 18-month-old Hispanic female had a history of delayed umbilical cord separation, recurrent necrotizing skin lesions, and gingivitis. Her neutrophils were found to lack detectable CD11/CD18 adhesion glycoproteins and were deficient in adhesion-dependent functions. She succumbed to necrotizing enterocolitis, peritonitis, and pneumonia following sudden cardiorespiratory collapse. Postmortem examination revealed multiple regions of mucosal ulceration and bacterial and fungal overgrowth with complete lack of an acute inflammatory response. Impaired neutrophil emigration from blood vessels into injured tissue appears to have been the basis of this patient's disease. Some of the many foci of bronchopneumonia, in contrast, contained numerous neutrophils. Lymphoid tissue, including the thymus, was severely depleted of lymphocytes. These findings support the concepts that neutrophils can emigrate in response to certain stimuli via CD18-independent mechanisms and that severe deficiency of CD18 is associated with compromised function of lymphocytes in vivo.


Polymorphism of the tumor necrosis factor region in relation to disease: an overview.

HLA antigens have been shown to be associated with several immunoinflammatory diseases. The mechanisms by which these antigens confer susceptibility to disease continue to be of major interest. Rapid progress has been made in the elucidation of the structure and function of class I and II MHC molecules, and several genes located within the HLA complex have been identified which are potentially involved in immunologic processes. Because of the HLA localization of the TNF-alpha and -beta genes and the biologic activities of the gene products, recent investigation has focused on a possible role of polymorphic TNF genes in the pathogenesis of HLA-associated diseases. Allelic variations have only been detected in the TNF-beta gene. No evidence has been found so far that a particular TNF-beta allele contributes significantly in the susceptibility to the diseases studied. Although it has been postulated that the TNF beta*2 allele contributes to susceptibility to IDDM in HLA-DR3, 4 heterozygous individuals, a larger group of HLA-typed patients and controls is needed to provide more conclusive evidence for this hypothesis. The increasing number of genes of unknown function encoded by the class III region leaves the possibility that the observed HLA associations in some diseases may be related to the presence of these genes. In AS, the lack of association with the TNF-beta alleles furthermore supports the function of the HLA-B27 molecule in the disease and underlines the improbability that HLA-B27 is merely a marker for a closely linked susceptibility gene.


Histiocytes in familial and infection-induced/idiopathic hemophagocytic syndromes may exhibit phenotypic differences.

Familial hemophagocytic syndrome (FHS) and infection-associated hemophagocytic syndrome (IAHS) usually present with fever, pancytopenia, hepatosplenomegaly, signs of hepatic dysfunction, bleeding diathesis, and neurological manifestations. FHS is almost uniformly fatal, and IAHS is associated with high mortality. The only distinguishing characteristics are lack of family history and association with infection in the latter. Despite this, sporadic cases of FHS and culture-negative examples of IAHS (idiopathic HS) can be difficult to distinguish and the distinction may have important implications for treatment and family planning. We evaluated the immunophenotype of the macrophages (M phi s) in frozen tissue sections from three cases of hemophagocytic syndrome using a very large panel of monocyte/M phi-associated monoclonal antibodies and an immunoperoxidase technique. The clinical and laboratory features suggested that two were examples of FHS (one with strong family history) and that the third was IAHS/idiopathic HS. The results supported the clinical impressions by showing that the antigenic phenotypes of the FHS cases were nearly identical and different from that of the case of presumed IAHS/idiopathic HS. Specifically, M phi s from the FHS cases expressed complement receptors, 1, 2, and 3 (CD35, CD21, and CD11b, respectively), the monocyte antigen CD36, and the "activation" antigens CD25 (IL2-R) and CD30 (Ki-1), while those from the IAHS/idiopathic case did not. These studies also demonstrated that the M phi s in these cases exhibited some phenotypic differences from those in control tissues, that is, expression of the pan-M phi antigen CD14, the M phi subset antigen identified by antibody G16/1, complement receptors, certain monocyte antigens, and M phi "activation" antigens.(ABSTRACT TRUNCATED AT 250 WORDS)


[Treatment of acute pain in a general hospital: opinions of physicians and nurses].

A survey was carried amongst physicians and nurses of a general hospital, in order to know their opinion about acute pain treatment. Out of 106 physicians and 153 nurses questioned, 72 and 105 respectively answered the questionnaire. Two thirds of them though that analgesic treatment was currently good, although, it could be improved if they increased their knowledge about it. Twenty nine per cent of physicians thought that their patients were receiving lower doses than what they had prescribed and that this fact could be responsible for the treatment failure. Those questioned believed that approximately 30% of patients treated with opium derivatives for over a week could develop addiction problems. Our study confirmed the existence of inadequate attitudes towards the need for analgesics in patients with acute pain.


Serum and tissue transglutaminase correlates with the severity of inflammation in induced colitis in the rat.

Simple rat models of acute and chronic colonic inflammation were used to study the behaviour in serum and mucosa of transglutaminase (TG), an enzyme recently found to be reduced in serum of patients with inflammatory bowel disease (IBD) and related to the activity index of the disease. In the first model the intraluminal administration of 400 mM lactic acid in the colon caused an acute inflammation resembling that of florid ulcerative colitis in humans. In the second, intraluminal administration of the hapten 2,4,6-trinitrobenzenesulphonic acid (TNB) (10 or 30 mg) in 0.25 ml of ethanol as a 'barrier breaker' produced a chronic inflammatory disease. The results showed a reduced TG activity in colon of rats in both acute and chronic induced colitis (447 +/- 75 versus 1344 +/- 59 mU/g protein (p less than 0.001) and 484 +/- 59 versus 1204 +/- 75 mU/g protein (p less than 0.001)). This decreased activity was related to the severity of mucosal damage, which was dose-dependent. Moreover, in severe colitis the immunohistochemistry showed a TG location in repairing tissue. Serum TG activity was decreased after TNB administration (1.36 +/- 0.05 versus 3.44 +/- 0.20 mU/ml (p less than 0.001)) but not after lactic acid treatment (3.97 +/- 0.11 versus 3.78 +/- 0.16 mU/ml). In summary, the reduction of TG activity in both tissue and serum when the damage is stabilized reflects the altered morphofunctional integrity of the colon and suggests that serum assay of this enzyme could be a simple marker of intestinal mucosal status in IBD.


Flow-cytometric analysis of growth-regulatory peptides and their receptors in Barrett's oesophagus and oesophageal adenocarcinoma.

The conventional assessment of the premalignant potential of Barrett's oesophagus is unsatisfactory. However, it has recently been shown that abnormalities of growth-regulatory peptides and their receptors may be important in the pathogenesis of this condition. In an attempt to improve the diagnostic and prognostic criteria we have studied 21 consecutive patients with Barrett's oesophagus and 7 others with adenocarcinoma of the oesophagus. In each patient biopsy specimens were taken from the columnarlined oesophagus or the adenocarcinoma and from the gastric cardiac mucosa for routine histologic evaluation. Immediately adjacent specimens were taken from both the Barrett's mucosa or adenocarcinoma and from the gastric mucosa for flow-cytometric study. The latter samples were disaggregated and labelled with antibodies to epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and epidermal growth factor receptor (EGF-R). The flow cytometer selected cells labelled with each antibody and expressed them as a percentage of the total number of disaggregated cells (average, 5500 cells). Epidermal growth factor receptors were expressed in a greater number of cells from Barrett's mucosa, with the intestinal type or those with dysplasia, than in gastric cardiac mucosa (p less than 0.05). All seven adenocarcinoma had many more cells expressing EGF, TGF-alpha, and EGF-R than normal gastric mucosa (p less than 0.01). We conclude that flow-cytometric evaluation of EGF-R can help in the understanding of the pathogenesis of Barrett's oesophagus.


[HIV-associated malignant lymphomas].

In a retrospective analysis of data from 35 cases with malignant lymphoma from a cohort of 2017 HIV-infected patients, the stage of HIV-disease, the CD4 counts at the time of diagnosis, and the use of antineoplastic agents or radiotherapy were correlated with outcome. 6 patients had Hodgkin's lymphoma (HL) and 29 non-Hodgkin-lymphoma (NHL). 11 of these lymphomas were classified according to the international working formulation (IWF) as high grade (H, I and J, respectively) and 8 as intermediate grade (G). 10 could not be classified. 22 patients with NHL had stage IV disease according to the Ann Arbor classification, all of whom had manifestations at extranodular sites. 23 patients with NHL were treated with multiagent chemotherapy (18 with m-BACOD or CHOP, 5 patients with various other regimens) and four of them had additional radiotherapy. One patient received radiotherapy only. Two of 24 treated patients showed complete and five a partial response. Median survival of patients without treatment (all of them in poor general condition at the time of diagnosis) was 1.8 months and treated patients survived a median of 5 months. The pretreatment CD4 count was the most important predictor of survival. Patients with prior Aids-diagnosis showed a tendency towards shorter survival. The observed remission rate indicates that HL in HIV-infected patients is better treatable than HIV-associated NHL. However, the overall outcome of HL in our patients was clearly less favorable compared to the course of HL usually seen in patients without HIV infection. The proportion of patients with HL among all patients with malignant lymphoma and HIV disease was unexpectedly larger in our cohort compared to others. Therefore, a possible association of HL and HIV infection, as addressed by several other authors, needs further clarification.


Efflux of glutamate produced by short ischemia of varied severity in rat striatum.

Evidence has accumulated suggesting that ischemia-induced neuronal damage may be linked to an extracellular overflow of glutamate. The purpose of this study was to provide new information about the time course of the increase in extracellular glutamate concentration associated with moderate and severe ischemia, and its relationship with electrical changes including anoxic depolarization. Changes in the extracellular concentration of glutamate were continuously monitored in the rat striatum by microdialysis. Ischemia was induced by four-vessel occlusion for 3 or 5 minutes, and in some cases its severity was increased with a neck tourniquet. The severity of ischemia was assessed by electroencephalogram and direct current potential recording to detect anoxic depolarization. In all experiments, the extracellular glutamate concentration began to increase shortly after the onset of ischemia and steadily rose throughout the ischemic period. Increases up to 35.0 mumol/l (2-3 mumol/l baseline; p less than 0.005) were observed when ischemia provoked the rapid occurrence of a large and sustained anoxic depolarization. Relatively smaller but still significant increases (6.9 mumol/l; p less than 0.005) were observed in penumbral conditions (electroencephalogram loss without anoxic depolarization). Glutamate began to be cleared immediately after reperfusion and 90% of released glutamate was cleared within 5 minutes, even when the preceding ischemia had been severe. We propose that the extracellular glutamate concentration may not reach critical levels during short episodes of penumbral ischemia, but this might happen with a longer ischemic period.


Genomic analysis of Theileria sergenti stocks in Japan with DNA probes.

Restriction fragment length polymorphisms of Theileria sergenti DNA from 18 different infections of cattle in 14 locations in Japan were analyzed by Southern blotting using T. sergenti genomic DNA fragments as probes. Probe pTs 2 hybridized with four fragments in BamHI digested piroplasm DNA, at 8.0, 7.3, 6.0 and 3.4 kb. Probe pTs 11-D1 hybridized with multiple fragments. With each probe, polymorphisms were observed among stocks from different locations. However, there was no correlation between the patterns of hybridization bands and the locations where parasites were collected. Analysis of the hybridization patterns of stocks obtained from individual cattle in the same grazing areas showed an almost identical pattern.


Preliminary human trial of inactivated golden hamster kidney cell (GHKC) vaccine against haemorrhagic fever with renal syndrome (HFRS).

An inactivated golden hamster kidney cell culture (GHKC) vaccine against haemorrhagic fever with renal syndrome (HFRS) has been developed in recent years. A monovalent GHKC vaccine (lot 88-17) was prepared with L99 strain of the rat-type hantavirus, adapted in suckling mouse brain, cultivated in GHKC, and inactivated with 0.025% formalin, and a preliminary trial of the vaccine was carried out in a small number of human volunteers with the approval of the Ministry of Public Health, PRC, in order to identify safety and antibody response of the vaccine. Three inoculations were made on days 0, 7 and 28 respectively, by the intramuscular route with 1 ml vaccine each time for every volunteer. No obvious side effect was observed in vaccinees within 3 days after each inoculation. All 12 vaccinees (10 received three inoculations, and two received two inoculations of the vaccine) showed positive seroconversion of IgG antibody (by IFAT and ELISA) and neutralizing antibody (by enzyme focus reduction neutralization test, EFRNT), and 10 of them were still seropositive 180 and 360 days after the first inoculation. These results suggest that this vaccine would be safe for human use, and could effectively induce IgG and neutralizing antibody responses.


On the application of mathematical models of schistosome transmission dynamics. II. Control.

Mathematical models have considerable potential as aids to the design of schistosome control programmes. This is because of the complex nature of the schistosome transmission cycle and the variety of control measures available, which make the comparative effectiveness of different control options extremely difficult to predict. This review aims to demonstrate how control can be incorporated in models of schistosome transmission dynamics, and to make explicit the assumptions and limitations of the models and their relationships with field data. A basic model is described which considers changes in the mean number of schistosomes per person. The criteria for the eradication of endemic infection and the potential for reducing levels of infection are discussed. The treatment of various control measures within this framework is reviewed. These include: chemotherapy (mass, selective and targeted), molluscicide application (blanket and focal) and other snail control measures, larval stage control, improved water supplies and sanitation, and health education. The incorporation of economic variables is also discussed. The choice between different control options depends on the relationships between schistosome epidemiology and the costs and effects of control. The evaluation of cost-effectiveness is a dynamic problem, and the outcome will depend on local conditions and constraints. Very general recommendations for the design of schistosome control programmes are unlikely to prove useful.


Identification of a surface metalloproteinase on 13 species of Leishmania isolated from humans, Crithidia fasciculata, and Herpetomonas samuelpessoai.

Promastigotes of thirteen species of Leishmania isolated from human patients, as well as L. enriettii, Crithidia fasciculata and Herpetomonas samuelpessoai, were examined for the expression of an amphiphilic, surface-oriented metalloproteinase by surface radioiodination of living cells, fractionation by Triton X-114 extraction and phase separation, and zymogram analysis by fibrinogen-SDS-PAGE. In all species of Leishmania, and the two monoxenous trypanosomatid parasites of insects, an ectoproteinase similar to the Promastigote Surface Protease, or PSP, was observed. In contrast, neither Phytomonas sp. nor 'Leishmania tarentolae' express a detectable surface metalloproteinase. The presence of the functionally conserved metalloproteinase at the surface of Crithidia and Herpetomonas suggest the enzyme may not be involved in the infection of the mammalian host by Leishmania, but rather contributes to the survival of the protozoan in the environment of the insect midgut.


Trypanosomiasis in cattle in Gambia: incidence, prevalence and tsetse challenge.

The incidence of trypanosome infections, measured by a Berenil Index in experimental herds of 10 Zebu and 10 N'Dama cattle, was compared with tsetse challenge and with the prevalence of parasitaemia in local N'Dama at three villages in Gambia. Tsetse challenge was more strongly correlated with the incidence of parasitaemia in the Zebu than in the N'Dama. There was a strong correlation between prevalence and incidence of infection in the N'Dama. There was no correlation, however, between prevalence of infection in cattle and tsetse challenge unless the data were offset by 3-5 months. The Berenil Index in the Zebu increased at about twice the rate as in the N'Dama under corresponding levels of challenge. It is concluded that whereas incidence of infection in susceptible animals is best measured independently, it can, under stable conditions, be inferred from an assessment of tsetse challenge.


Maintenance therapy: is there still a place for antireflux surgery?

Effective and safe maintenance medical therapy for uncomplicated reflux esophagitis is now feasible with omeprazole and it is likely that other H+K+ATPase blockers, and possibly very high dose H2 receptor antagonist regimens, will also be acceptable. In addition, many patients with ulceration, strictures, and Barrett's esophagus will respond to conservative medical therapy and a proportion of patients with erosive esophagitis may remain in remission with cisapride or with low dose H2 receptor antagonists, if disease is less severe. Thus, there is now a medical "gold standard" against which surgical therapy for uncomplicated esophagitis must be judged and it is essential that all future studies be conducted with clearly defined criteria for the assessment of the symptoms and endoscopic signs of esophagitis and its complications. As ever, the patient's wishes are paramount, but he or she must be allowed to select his or her therapy on the basis of a balanced and fully informed assessment of the long-term and short-term risks of all therapeutic modalities. The burdensome prospect of lifelong tablet ingestion and its potential dangers must be weighed against the alternative, in up to 30% of cases, that surgery may produce dysphagia, gas bloat, or dumping with no guarantee of a long-term cure.


A scanning electron microscopic study of the sporogonic development of Plasmodium falciparum in Anopheles stephensi.

The full development of Plasmodium falciparum in Anopheles stephensi mosquitoes was studied by scanning electron microscopy. Ookinetic development was described from in vitro cultures. Growing oocysts beneath the basal lamina of the midgut wall mechanically stretch this lamina until it is torn and displaced by day 7. In young oocysts the wall appears smooth. In older oocysts wrinkles in the wall are visible after routine fixation. Osmium tetroxide postfixation greatly reduced the occurrence of these wrinkles. Intracapsular development of sporozoites was visualized after mechanical manipulation of the oocysts during sample preparation. In contrast to P. berghei, no ectopic development was seen in P. falciparum in the mosquito midgut. The mechanism of sporozoite escape from the oocyst appears to be similar to that described for rodent malaria. Fracturing of salivary glands provided the first view by scanning electron microscopy of sporozoites located in proximal and distal gland cells and in the draining duct.


Chemical composition of Litomosoides carinii microfilarial sheaths.

Litomosoides carinii microfilariae were exsheathed by freezing and thawing, and the sheaths were separated by filtration. Samples of pure sheaths thus obtained were hydrolyzed, methanolyzed or oxidized with nitric acid under pressure at 300 degrees C, respectively, and were analyzed for amino acids, sugars, fatty acids or for metal ions and phosphorus. Almost 75% of the sheath dry weight could thus be accounted for. Amino acids (55 weight %) were the major constituents, and amongst these glutamine and proline (approximately 11% each). The detection of 2% cysteine/cystine indicated the possible presence of disulfide crosslinks. Besides amino acids, approximately 8% of sugars--roughly equimolar amounts of (N-acetyl)galactosamine and uronic acids--1.5% of monovalent cations (Na+ and K+) and 9.5% of phosphate were detected. No appreciable amounts of fatty acids, neutral sugars, neuraminic acid, or (N-acetyl)glucosamine (i.e. no chitin) were found.


The rapid development of drug-resistance by Trypanosoma evansi in immunosuppressed mice.

The effect of immunosuppression on the development of drug resistance by trypanosomes was investigated in mice infected with Trypanosoma evansi. As a result of frequent passage in immunosuppressed mice given subcurative drug treatments clones of T. evansi rapidly developed high levels of resistance to mel Cy, diminazene aceturate and isometamidium chloride. Similar protocols in normal immunocompetent mice infected with the same parent clones did not lead to the development of drug-resistance. The resistant populations developed in immunosuppressed mice maintained their high levels of resistance when tested in normal mice. The mel Cy resistant clone was tested for cross-resistance to other trypanocides and was found to be also highly resistant to diminazene and pentamidine. The results indicate that impairment of the host immune system may lead to the rapid development of drug-resistance by T. evansi under experimental conditions in mice and may possibly play a role in the development of drug resistance by trypanosomes in the field.


Evaluation of recombinant trypomastigote surface antigens of Trypanosoma cruzi in screening sera from a population in rural northeastern Brazil endemic for Chagas' disease.

A perfect serologic test for infection with Trypanosoma cruzi does not exist. This study uses recombinant T. cruzi surface proteins in the antibody capture enzyme linked immunoabsorption assay (ELISA); and compares this approach to the more standard immunofluorescence assay (IFA). Three recombinant antigens are studied: F1-160 corresponding to the 160 kDa flagellar associated surface protein of trypomastigotes (the motile form of T. cruzi in mammalian infections); and SA 85-1.1 and 1.2 corresponding to different members of the 85 kDa family of surface proteins expressed by trypomastigotes and amastigotes (the replicative, non-motile form of T. cruzi in mammalian infections). Each recombinant antigen is found to be highly specific (range 86-94%) but relatively insensitive (range 36-52%) when used to screen for antibodies to T. cruzi. Defining seropositivity as reactivity to any of the three recombinant antigens markedly increases the sensitivity (72%) with only a minor reduction in specificity (82%). Thus, employing recombinant T. cruzi antigens to screen for T. cruzi infection has promise, but improvements in sensitivity must be made before widespread utilization is recommended.


[Usefulness and safety of bunazosin hydrochloride in neurogenic bladder after prolonged administration].

Bunazosin hydrochloride (Ea-0643), a selective alpha 1-blocker, was administered to 14 patients with neurogenic bladder over prolonged periods of time in order to determine its efficacy and safety. Subjective symptoms were classified into 4 grades, and their response assessed after 12 weeks of treatment. The proportion of patients showing improvement by at least one grade was 50.0% for retarded urination, 16.7% for prolonged urination, 25.0% for urinary stream condition, 25.0% for abdominal pressure at voiding, and 28.6% for residual urine. Objective symptoms were also assessed after 12 weeks of treatment, and a statistically significant improvement was recognized in the volume of spontaneously voided urine, the maximum and mean flow rates on uroflowmetry. It should be noted that both of those flow rates had improved significantly only 2 weeks into the treatment. The degree of improvement in subjective and objective symptoms and the degree of general improvement were all higher at week 12 than at week 2 of treatment. Current knowledge of the mechanism of action of this drug, coupled with the observations made in this study, suggests that, once it has improved the urodynamics, it exhibits a sustained effect for prolonged periods of treatment. However, further studies are warranted concerning the mechanisms of the pharmacological action of the drug from a pathological viewpoint. The proportion of patients in whom Ea-0643 was judged to be useful at 12 weeks of treatment was 41.7%, but when the assessment of 'slightly useful' was taken into consideration, the usefulness rate rose as high as 91.7%. Stomatitis was observed in only one case as a side effect of this drug.(ABSTRACT TRUNCATED AT 250 WORDS)


Various cell types in human atherosclerotic lesions express ICAM-1. Further immunocytochemical and immunochemical studies employing monoclonal antibody 10F3.

The specificity of monoclonal antibody 10F3, generated to smooth muscle cells isolated from fetal human aorta, has been further explored in a series of biological, biochemical, and immunocytochemical studies. In the first assay, it was found that 10F3 could inhibit aggregation of phytohemagglutinin (PHA)-induced lymphocytes in a manner comparable to that of antibody RR1/1, an anti-intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody. In immunoprecipitation experiments followed by one-dimensional gel electrophoresis, both 10F3 and RR1/1 immunoprecipitated 90 kd proteins, with results suggesting that the two antibodies recognized different epitopes of the same molecule. A series of immunocytochemical studies on human atherosclerotic lesions was performed; using single-labeling techniques, 10F3-positive cells were found in the vessel wall and in lesions of virtually all specimens of fatty streaks and fibrous plaques. Using double-labeling techniques, 10F3-positive macrophages and 10F3-positive smooth muscle cells were found; however, there were also a significant number of non-smooth muscle, nonmacrophage 10F3-positive cells. These studies demonstrate that 10F3 identifies ICAM-1, and that this protein is expressed on a variety of cell types in human atherosclerotic lesions. ICAM-1 may represent a developmentally regulated protein that is expressed in fetal but not adult mesenchymal cells, but can be re-expressed in pathologic processes such as atherosclerosis.


Mechanisms for anoxic survival in the vertebrate brain.

When energy supplies to the mammalian brain are significantly reduced by anoxia, for a very short time energy requirements are curtailed by such routes as the suppression of synaptic transmission, while energy supply is enhanced by an increase in cerebral blood flow and an increase in glycolysis. The reduction of ATP consumption is insufficient to match the greatly curtailed supply of ATP coming from anaerobic glycolysis and the hydrolysis of PCr, and within minutes ATP falls, there is a loss of ion homeostasis with depolarization, and cell death occurs. The anoxia-tolerant species, like the turtle, appear to employ similar mechanisms to reduce energy expenditure, but in addition to such means as increases in inhibitory neurotransmitters and the manipulation of ion channel activities, they are able to reduce the energy costs to a level that can be met by a greatly reduced supply from anaerobic glycolysis. In this way ATP levels are maintained for many hours, and anoxic depolarization, with its concomitant consequences such as an uncontrolled release of excitatory amino acids are avoided. The greater anoxic tolerance of the mammalian neonate brain is due in part to intrinsic lower metabolic requirements and, perhaps through mechanisms similar to those in the turtle, to suppress metabolic demand. Studies of the survival mechanisms of anoxia-tolerant brains of such species as the turtle and crucian carp are not only of value for investigating a remarkable neuronal adaptation, but they promise to provide a valuable model for the study of the etiology of hypoxic damage and survival strategies in the mammal.


[How to evaluate the cost/effectiveness ratio of different therapies of coronary disease].

The results of epidemiologic studies on the efficacy of different strategies of prevention or improvement of the prognosis of coronary artery disease are generally expressed in terms of percentage reduction of risk; for example, the treatment of hypercholesterolaemia reduces the risk of coronary death by 21%. In order to improve the assessment of the efficacy of these approaches the authors propose to take into account the number of subjects which needs to be treated each year to prevent one cardiovascular event more than the control group (for example, in hypercholesterolaemia, 1,736 patients). This number depends on the reduction of risk and also on the incidence of complications in the control group. Using this method, the authors classified different therapeutic strategies in order of their efficacy: thrombolytic therapy in the acute phase of myocardial infarction, then aortocoronary bypass grafting of left main coronary or triple vessel disease, secondary prevention with stopping smoking, and betablocker therapy. Finally, primary prevention with anti-smoking campaigns, treatment of hypertension and hypercholesterolemia. Based on this figure and knowing the annual cost of patient treatment, it is possible to calculate a cost-effectiveness ratio for each of these therapeutic interventions.


Characterization of a new compound, S35b, as a guanylate cyclase activator in human platelets.

The effects of S35b (4-methyl-3-phenyl sulfonylfuroxan), a new phenyl sulfonylfuroxan compound, were investigated on human platelets activated by different agonists. Platelet aggregation evoked by arachidonic acid (AA), collagen, ADP and thrombin was inhibited by the drug in a dose-dependent manner. S35b inhibited the AA-induced increase of cytosolic free Ca2+ ([Ca2+]i) and production of malondialdehyde. A primary action of the compound on cyclooxygenase is unlikely since: (1) U-46619 (15s-hydroxy-11,9-[epoxymethano]-prosta-5Z,13E-dienoic acid, a stable epoxymethano analog of prostaglandin H2) could not reverse the inhibitory effect of S35b on AA-induced aggregation and [Ca2+]i increase; (2) U-46619-induced aggregation and [Ca2+]i rise were inhibited by S35b; and (3) at high collagen concentrations platelet aggregation (which is unresponsive to aspirin under such conditions) was blocked by S35b as well. Thus the drug action is likely to be exerted at an early step of the platelet activation pathway. The elevation in the platelet cGMP level evoked by S35b in a time- and concentration-dependent manner can account for the inhibitory effect: increased cGMP levels could interfere, for instance, with G protein-phospholipase C coupling and subsequent phosphoinositide hydrolysis.


Antimalarial activity of orotate analogs that inhibit dihydroorotase and dihydroorotate dehydrogenase.

Dihydroorotase and dihydroorotate dehydrogenase, two enzymes of the pyrimidine biosynthetic pathway, were purified from Plasmodium berghei to apparent homogeneity. Orotate and a series of 5-substituted derivatives were found to inhibit competitively the purified enzymes from the malaria parasite. The order of effectiveness as inhibitors on pyrimidine ring cleavage reaction for dihydroorotase was 5-fluoro orotate greater than 5-amino orotate, 5-methyl orotate greater than orotate greater than 5-bromo orotate greater than 5-iodo orotate with Ki values of 65, 142, 166, 860, 2200 and greater than 3500 microM, respectively. 5-Fluoro orotate and orotate were the most effective inhibitors for dihydroorotate dehydrogenase. In vitro, 5-fluoro orotate and 5-amino orotate caused 50% inhibition of the growth of P. falciparum at concentrations of 10 nM and 1 microM, respectively. In mice infected with P. berghei, these two orotate analogs at a dose of 25 mg/kg body weight eliminated parasitemia after a 4-day treatment, an effect comparable to that of the same dose of chloroquine. The infected mice treated with 5-fluoro orotate at a lower dose of 2.5 mg/kg had a 95% reduction in parasitemia. The effects of the more potent compounds tested in combination with inhibitors of other enzymes of this pathway on P. falciparum in vitro and P. berghei in vivo are currently under investigation. These results suggest that the pyrimidine biosynthetic pathway in the malarial parasite may be a target for the design of antimalarial drugs.


[Takayasu arteritis associated with heart valve diseases (pulmonary and aortic) and arteritis (coronary and renal)].

The most severe arteritis due to Takayasu's disease are those related to renal and coronary arteries. The first one because it produces severe arterial hypertension and the second one because it puts the patient in high risk of suffering either myocardial ischemia or infarction. These situations worsen when this entity is associated to valvular heart lesions. The authors present the clinical cases of two female patients with Takayasu's disease. One of them in acute phase of the illness, where coronary arteritis, mild coarctation of the aorta, right pulmonary artery stenosis, and pulmonary valve stenosis were present. The second patient was seen during the remission phase of the disease with obstruction of the left subclavicular artery, renal arteritis, severe arterial hypertension and aortic valve insufficiency. The authors discuss the prognosis of patients with Takayasu's disease associated to valvular heart disease and its role in the etiology of pulmonary valvular stenosis. Finally, the authors point out the importance of recognizing the active and non active phases of the Takayasu's disease in relation of the adequate stage for surgical treatment of the lesions caused by this disease.


The cerebroside sulfate activator from pig kidney: derivitization, cerebroside sulfate binding, and metabolic correction.

Highly purified cerebroside sulfate activator from pig kidneys was characterized by a number of chemical and biological procedures. Methods for chemical modifications were evaluated in an attempt to obtain biologically active derivatives. Iodination, dabsylation, and to a lesser degree reductive methylation provided useful products with good retention of cerebroside sulfate activator activity. Other procedures resulted in largely inactive derivatives or losses in both protein and biological activities. Attempts at renaturation of cerebroside sulfate activator subjected to various denaturing conditions appeared to be successful in many instances, but it was uncertain if the protein structure had actually been disrupted. The binding of cerebroside sulfate by activator was estimated by gel filtration under conditions similar to those of its assay. The formation of a relatively stable 1:1 complex was observed, collaborating results with the human protein. The complex was stable enough to be isolated and shown to be an efficient substrate for arylsulfatase A. The effectiveness of the pig kidney cerebroside sulfate activator for correcting the metabolic defect in activator-deficient human fibroblasts was compared with human materials. The pig kidney protein was taken up more efficiently by the cells and resulted in a better metabolic correction than material from human liver, but was somewhat less effective than a preparation from human urine.


P-glycoprotein overexpression cannot explain the complete doxorubicin-resistance phenotype in rat glioblastoma cell lines.

We have associated pharmacological studies to a semi-quantitative evaluation of P-glycoprotein(s) expression, to establish if classical multidrug resistance (MDR) could account for the complete resistance phenotype exhibited by progressively doxorubicin-resistant rat glioblastoma cells. Three resistant variants (C6 0.001, C6 0.1 and C6 0.5) of the C6 glioblastoma cell line (C6 S) were selected by long-term culture in the presence of three concentrations of doxorubicin (0.001, 0.1 and 0.5 microgram.ml-1 respectively). The degree of doxorubicin resistance was respectively 7, 33 and 400, and all the cell variants were cross-resistant to m-AMSA, etoposide and vincristine. Doxorubicin incorporation was reduced similarly in all resistant cells, irrespective of the level of resistance. When exposed to their respective doxorubicin IC50, the 7-fold resistant cells had the same intracellular drug incorporation as the sensitive cells, whereas the 33-fold and 400-fold resistant cells could incorporate respectively 3.7 and 17 times more drug. The ratio of doxorubicin exposures required for 50% DNA synthesis inhibition and 50% growth inhibition was dependent on the degree of resistance; this ratio was 12.8 in C6 S, 11.6 in C6 0.001, 6.3 in C6 0.1 and 1.8 in C6 0.5. P-glycoprotein(s) overexpression was of the same magnitude as the resistance factor in variants C6 0.001 and C6 0.1, but was lower than resistance factor in variant C6 0.5. Reversal of drug incorporation by verapamil was complete in all resistant cell lines; however, reversal of doxorubicin cytotoxicity was complete only in the 7-fold resistant line and was only partial in the most resistant lines, which remained 10-fold and 20-fold resistant to doxorubicin. These results suggest that classical MDR was the first phenotype selected by doxorubicin in C6 0.001, whereas mechanism(s) of doxorubicin resistance other than classical MDR are added in the most resistant lines.


Facilitation of rapid-sequence intubation with large-dose vecuronium with or without priming.

To determine the effect of priming on the intubation and onset times of vecuronium 0.3 mg/kg. Randomized, unblinded study. Operating rooms and postanesthetic recovery unit of a university-affiliated general hospital. Thirty female ASA physical status I and II patients scheduled for intraperitoneal surgery divided into two groups of 15 each. Anesthesia was induced and maintained with sufentanil, droperidol, thiopental sodium, and nitrous oxide in oxygen. Patients in Group 1 were given vecuronium 0.015 mg/kg 4 minutes before induction and vecuronium 0.285 mg/kg 1 minute after induction. Patients in Group 2 received a single 0.3 mg/kg dose of vecuronium 1 minute after thiopental sodium. The ulnar nerve was stimulated every 10 seconds with train-of-four supramaximal impulses of 0.2 millisecond duration at 2 Hz. The compound electromyogram (EMG) of the adductor pollicis was continuously recorded. The trachea was intubated when the amplitude of the EMG decreased to 15% to 25% of control. At the end of surgery, residual neuromuscular block was reversed with edrophonium 0.75 mg/kg. All patients in Group 1 could be intubated in 80 seconds or less, and the longest onset time was 120 seconds. In Group 2, the longest intubation time was 140 seconds, and the longest onset time was 200 seconds. Clinical durations in both groups were unpredictable, ranging from 47 to 185 minutes in Group 1 and from 63 to 160 minutes in Group 2. Ten of the 30 patients required an additional 0.5 mg/kg of edrophonium for antagonism of the residual neuromuscular block. There were no significant changes in heart rate or blood pressure attributable to vecuronium. Seventy-five percent to 85% neuromuscular block of the adductor pollicis, required for atraumatic tracheal intubation, developed in 80 seconds or less when vecuronium 0.3 mg/kg was administered in divided doses and in 140 seconds or less when it was injected as a single bolus dose. Clinical duration of vecuronium 0.3 mg/kg is long and unpredictable, and reversal of residual neuromuscular block may require larger doses of anticholinesterases. It is recommended that an intubating dose of vecuronium 0.3 mg/kg be used only in patients undergoing long surgical procedures that require prolonged postanesthetic mechanical ventilation.


Germ cell-Sertoli cell interactions and production of testosterone by purified Leydig cells from mature rat.

The addition of seminiferous tubule (ST) culture medium (STM) prepared from testes of either busulfan-treated (Bus) or cryptorchid (Cryp) or genetically sterile (hd) rats, to Percoll purified Leydig cells leads to a further increase of LH-stimulated testosterone (T) output (26, 43 and 14%, respectively). Taking into account that the Sertoli cell number per cm of ST is 2.6, 1.8 and 1.4-fold greater in Bus, Cryp and hd rats than in controls, the above STM effects on T output, expressed per 10(6) Sertoli cells are in fact lower (63, 44 and 43%, respectively) that those of control STM. Similar results have been obtained for the STM transferrin levels which are decreased, 74, 67 and 45%, respectively in Bus, Cryp and hd animals. So, it is likely that the Sertoli cell secretion of both the paracrine factor involved on Leydig cell T production and the transferrin is influenced mainly by spermatids and to a lesser extent by spermatocytes of mature rat testis.


Duration of antagonizing effect of RU486 on the agonist induction of tyrosine aminotransferase via glucocorticoid receptor.

The duration of the antagonizing activity of RU486 on tyrosine aminotransferase (TAT) induction and the glucocorticoid receptor in rat liver was studied. A single dose of RU486 (10 mg/kg) caused occupation of the cytosol glucocorticoid receptor in rat liver at 1 h. During this time no nuclear binding of [3H]dexamethasone ([3H]Dex) receptor complex was recorded, and TAT induction was completely blocked. TAT inducibility recovery parallelled receptor binding in both the cytosol and the nuclei, reaching maximum at 12 h. In contrast, nuclear binding recovered in 24 h, and [3H]Dex receptor binding in cytosol 48 h after RU486 application. It is concluded that the inhibitory effect of a single dose of RU486 on TAT induction is of rather short duration. At concomitant presence of agonist and antagonist in vivo, no direct correlation between agonist receptor occupancy and TAT induction could be observed.


Clinical interactions with alpha-2-adrenergic agonists in anesthetic practice.

With the continued use of alpha-2-adrenergic agonists in anesthetic practice, careful attention should be given to the potential for drug interactions. Based on a review of the basic and applied pharmacology of this class of compound, we have made recommendations for the safe and efficacious use of alpha-2-adrenergic agonists in the clinical setting.


Two liver-enriched trans-acting factors support the tissue-specific basal transcription from the rat tyrosine aminotransferase promoter.

The rat tyrosine aminotransferase gene (TAT) is a glucocorticoid-inducible gene, specifically expressed in liver. Using gel retardation assays, we have shown that its promoter (nt + 1 to -350; TAT.35) binds a combination of both ubiquitous and liver-specific trans-acting factors. Cis-acting sequences spanning: (i) nt -65 to -85 bound NF-Y, an ubiquitous "AACCAAT" box binding factor; (ii) nt -157 to -171 bound a liver-enriched member of the NF1 gene family [NF1Liver (NF1L hereafter)]; (iii) nt -266 to -281 bound the liver specific factor HNF1; and (iv) nt -283 to -288 bound ubiquitous "CCAAT" box binding factor(s). Moreover, the TAT gene promoter was able to drive liver-specific basal transcription, even in an in vitro assay using TAT-expressing (liver) vs non-expressing (spleen) crude nuclear extracts (NEs). Competition studies in transcription with both unmutated and mutated ds-oligonucleotides (ds-oligos) demonstrated that NF1L and HNF1 supported approx. 60 and 25% of the basal transcriptional activity sustained by TAT.35 in the liver, respectively. Neither of these oligos affected the very low level of transcription sustained by spleen NEs. This suggests a minor role for HNF1 in liver-specific basal TAT gene expression, consistent with previous observations with dedifferentiated C2 hepatoma cells (which does not express HNF1) [Deschatrette and Weiss. Biochimie 56 (1974) 1603-1611 and Cereghini et al. EMBO Jl9 (1990) 2257-2263]. Competition studies in liver-specific in vitro transcription with ds-oligo -265/-290 yielded a 90% inhibition, suggesting either that sequences spanning nt -283 to -288 sequester "CCAAT-box" binding factor(s) that may be relevant elsewhere for TAT promoter function (e.g. NF-Y which interacts with nt -65 to -85), or that such a factor interacts functionally with HNF1.


Excitatory amino acid regulation of gonadotropin secretion: modulation by steroid hormones.

Excitatory amino acids (EAAs) can potently modulate gonadotropin secretion in the male rat and monkey. In the present study we examined the effect of EAAs on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the female rat under low estrogen (ovariectomized) and high estrogen (proestrus) backgrounds. In ovariectomized immature female rats N-methyl-D-aspartate (NMDA) inhibited LH but not FSH secretion at 30 min post-injection. In contrast, NMDA potently stimulated LH but not FSH secretion when administered on proestrus to adult female rats. Both glutamate and kainate were also found to stimulate LH but not FSH secretion in estrogen-treated ovariectomized immature rats. This study suggests that EAA neurotransmission may be an important component in the expression of gonadotropin surges and that EAA effects appear to be subject to gonadal steroid regulation.


Colocalization of vasoactive intestinal polypeptide and GABA immunoreactivities in a population of wide-field amacrine cells in the rabbit retina.

Vasoactive intestinal polypeptide (VIP) immunoreactive (IR) neurons in the rabbit retina constitute a population of wide-field amacrine cells. To better define this cell population, we examined the coexpression of VIP with other putative retinal transmitters or their biosynthetic enzymes, including gamma-aminobutryic acid (GABA), tyrosine hydroxylase (TH), and somatostatin (SRIF). Colchicine-treated retinas were immersion fixed in 4% paraformaldehyde. The retinas were cut either perpendicular or parallel to the vitreal surface and processed by double-label immunofluorescence techniques using antibodies directed to VIP, GABA, TH, and SRIF. The immunoreactive staining patterns obtained with these antibodies were the same as those described in previous studies. GABA-IR neurons were localized to the proximal inner nuclear layer (INL) and ganglion cell layer (GCL) and processes were distributed throughout the inner plexiform layer (IPL). TH- and SRIF-IR neurons were sparsely distributed to the proximal INL and GCL, respectively. TH-IR processes ramified in laminae 1, 3, and 5, and SRIF-IR processes in laminae 1 and 5 of the IPL. Colocalization experiments showed that all VIP-IR neurons contain GABA immunoreactivity. In contrast, colocalization of VIP and TH or SRIF immunoreactivities was never observed. These results demonstrate that VIP-IR wide-field amacrines of the rabbit retina make up a neurochemically and morphologically distinct subpopulation of the GABA-IR amacrine cell population. Furthermore, VIP-IR amacrine cells constitute a distinct group with respect to the TH- and SRIF-IR amacrine cells.


Identification of distinct P-glycoprotein gene sequences in rat.

In higher vertebrates, P-glycoprotein is usually encoded by a small family of genes. We have determined that the rat contains three P-glycoprotein genes and have cloned distinct genomic fragments containing the putative 3' untranslated regions of these P-glycoprotein genes. Sequence analysis indicates that the rat P-glycoprotein genes belong to the three P-glycoprotein classes identified in mammals. These cloned sequences will be useful for delineating the expression of P-glycoprotein genes in the rat. We have also isolated a fourth clone which contains only a short, but highly conserved P-glycoprotein domain. This clone appears not be a member of the P-glycoprotein gene family, and its relationship to P-glycoprotein is unknown.


Analysis of the 5' flanking region of the rat proliferating cell nuclear antigen (PCNA) gene.

The proliferating cell nuclear antigen (PCNA), highly conserved among eukaryotes, is an auxiliary factor for DNA polymerase delta. In this report we sequenced 1560 nucleotides (nt) of the 5' flanking region of the rat PCNA gene and located the transcription initiation site. The sequence contains 1435 nt upstream of the cap site and promotes transcription of a linked heterologous reporter gene in rat, mouse and human cells. Transient expression assays using a series of 5' deletion mutants revealed that 240 nt of the upstream sequence are sufficient for full promoter activity. Three GC boxes and several other binding sites of transcription factors were observed, but neither a TATA nor a CCAAT sequence was found in this region. The results also suggested the existence of a negative regulatory element(s) between -968 and -691. Cotransfection with early region 1 (E1) genes of human adenoviruses activated the expression of the reporter gene, suggesting that an E1-responsive element is located at the proximal promoter region within 81 nt upstream of the transcription initiation site.


Drug addiction and AIDS: highlights of the 1st European Congress.

The 1st European Congress on 'Drug Addiction and AIDS' was held in Vienna, Austria, February 21-23 1991. This conference represented scientists from all areas of Europe and North America. The co-ordinators and the international scientific board offered an exciting programme with eight workshops in clinical, medical and management tracts; there were four plenary sessions with international, national and local experts, exhibits and receptions. With the impact of AIDS and the changes in Eastern Europe, we must now, more than ever before, rethink our strategies to improve effective treatment for substance abusing patients.


Prediction of outcome after first recurrence of breast cancer.

To assess the independent power of certain clinical, histological, and morphometric variables to predict survival after first recurrence of breast cancer. Long term follow up study. Departments of surgery and pathology, University Hospital. 212 patients (from a consecutive series of 517) who developed recurrence after primary treatment of breast cancer between 1968 and 1990. Re-examination of histology of primary tumours, follow up of patients, and calculation of predictive score by Cox's regression analysis. The nodal status at the time of diagnosis (p less than 0.001), the SD of the nuclear area (p = 0.01), the degree of tubule formation (p = 0.003), and the age of patient, were all independent predictors. The most important predictor of survival was the prognostic score derived from the coefficients of the Cox's model (p less than 0.0001). Survival after first recurrence can be accurately predicted by advanced histological analysis of the primary tumour tissue. Combination of independent predictors permits even more accurate estimation of survival time.


Increasing prevalence of abdominal aortic aneurysms. A necropsy study.

To analyse the prevalence of abdominal aortic aneurysms in the city of Malmö. Retrospective demographic study. Malmö General Hospital. Reports of all 45,838 necropsies done at the Department of Pathology, Malmö General Hospital 1958-1986. Abdominal aortic aneurysms were found in 4,300/100,000 men and 2,100/100,000 women. The mean annual age-standardised increase of aortic aneurysmal disease was 4.7% among men and 3.0% among women. The prevalence among men increased rapidly after the age of 55 and reached a peak of 5.9% at the age of 80; that among women increased after the age of 70 and reached a peak of 4.5% above the age of 90 years. The prevalence of aortic aneurysmal diseases has increased during the last three decades, and is age and sex-dependent.


A "new" intraabdominal artery. The pedicled right gastroepiploic artery for myocardial revascularization.

The right gastroepiploic artery (GEA) was used as a pedicled conduit for direct coronary artery revascularization in 20 patients presenting with more or less exhausted saphenous vein resources. The early angiographic patency of the GEA conduit appears to be satisfactory when it is connected to the right coronary artery system. A distinct disadvantage of GEA grafting is the necessity to enter the abdominal cavity, which may lead to probably rare and as yet unrecognized morbidity. Future abdominal surgery may injure the GEA conduit unless its topographic relations to the prepyloric antrum, liver and diaphragm are properly recognized. The surgeon must then be prepared to encounter antegastric, retrogastric, antehepatic, transhepatic and retrohepatic routes of the redirected intraabdominal artery. The present paper addresses this problem. Preoperative angiography of the celiac trunk and superior mesenteric artery may be helpful in decision-making when a patient reports or records show that a graft has been harvested from the abdominal cavity.


Laser hepatorrhaphy in albino rats.

The ability of low-power Nd-YAG laser to weld liver tears was studied in nine albino rats (average body weight 146 g) after induction of 11 liver tears. Laser hepatorrhaphy was successful in ten tears. Haemostasis was achieved with the laser technique in all 11 tears, including the single case of postoperative liver tear dehiscence. Bleeding from the site of a marker stitch was successfully controlled by two additional laser shots in one animal. Histologic studies of successfully welded liver tears were done on the first and third postoperative days.


Prevention of peritoneal adhesions in rats with verapamil, hydrocortisone sodium succinate, and phosphatidylcholine.

To assess the effectiveness of verapamil, hydrocortisone sodium succinate, and phosphatidylcholine in the prevention of experimental adhesions. Randomized trial. 80 rats. Laparotomy and intraperitoneal irrigation with saline 40 degrees C, then verapamil hydrochloride 1 mg/kg intravenously 15 min before, during, and after irrigation; or hydrocortisone sodium succinate 50 mg/kg intravenously half an hour before irrigation; or phosphatidylcholine 5.5 mg/kg orally eight days before and seven days after irrigation plus 0.5 mg/ml in the irrigation fluid; or no further intervention. Development of adhesions two weeks after irrigation, and completeness of wound healing. Adhesions developed in 13 of 19 control animals; 7 of 20 that were given verapamil; 6 of 20 that were given hydrocortisone; and 3 of 20 given phosphatidylcholine. Adhesions that developed in rats after laparotomy and intraperitoneal irrigation with saline at 40 degrees C can be significantly reduced by phosphatidylcholine.


Diagnostic accuracy and perforation rate in appendicitis: association with age and sex of the patient and with appendicectomy rate.

To see if diagnostic accuracy and perforation rate in acute appendicitis is associated with age and sex of the patients and with the appendicectomy rate. Retrospective study of consecutive patients from a defined population. Study of associations between diagnostic accuracy and perforation rate and appendicectomy rate in published reports. Jönköping county, Sweden. 3,029 patients operated on for suspected acute appendicitis from 1984-1989. Findings at laparotomy for acute appendicitis, confirmed with histological examination in 83% of the cases. Diagnostic accuracy was low at the extremes of age and in women (60% compared with 79% in men, p less than 0.001). When all intra-abdominal conditions were considered the percentage of negative laparotomies among women (24%) was twice that among men (12%, p less than 0.001). This difference between the sexes was also seen in nonfertile ages. Perforation rate was higher among men (18% compared with 13%, p less than 0.01) and at extremes of age. According to correlation analysis of published reports the perforation rate is unrelated to either diagnostic accuracy or appendicectomy rate while diagnostic accuracy is inversely associated with the appendicectomy rate. A low diagnostic accuracy is a problem mainly at extremes of age and in females. A low appendicectomy rate is associated with a high diagnostic accuracy, while the perforation rate is unaffected. A conservative attitude to exploration therefore seems justified.


Effect of appendicectomy on development of right inguinal hernia.

The effect of appendicectomy on the subsequent development of right inguinal hernia was investigated in 583 patients with hernias, 42 of whom had previously had appendicectomies. The incidence of right sided hernias was no greater among these patients than among those who had not had their appendixes removed. Neither sex was more prone to develop an inguinal hernia after appendicectomy, and no type of hernia (direct or indirect) predominated. The cause of right sided inguinal herniation after appendicectomy has been thought to be damage to the nerve supply of the inguinal muscles during the appendicectomy incision. All our 42 cases except two had had their appendicectomies through classic McBurney incisions, which were some distance away from the most common areas of nerve damage. We conclude that development of a right inguinal hernia is an unlikely complication of appendicectomy if a classic McBurney incision was used.


Effect of epidural and general anaesthesia compared with general anaesthesia alone in large bowel anastomoses. A prospective study.

To find out whether patients did better after operations that entailed a large bowel anastomosis if they were given combined epidural and general anaesthesia with spontaneous ventilation rather than standard general anaesthesia with muscle relaxation and ventilation. Prospective randomised trial. Specialist unit, teaching hospital. 80 patients undergoing large bowel anastomoses. Incidence of chest infection, wound infection, anastomotic breakdown, urinary tract infection, deep vein thrombosis, pulmonary embolism, median hospital stay and death. There were no differences between the groups, but the results were better during the trial period (1985-89) than during the period 1978-83. Factors that influence anastomotic healing are complex and improved surgical techniques, postoperative monitoring and patient care may account for the improvement in results compared with the earlier period.


Anorectal abscesses in immunosuppressed patients.

The results of surgery in 14 immunosuppressed patients with 17 anorectal abscesses are presented. Abscess incision was followed by almost immediate relief of pain. Healing was obtained in 15 cases, but two patients died of causes unrelated to surgery. Symptoms, therapeutic possibilities and prognosis are discussed. The authors conclude that surgery should be performed in all cases to prevent development of septicemia. Fluctuation should not be awaited, but surgery should be minimized if granulocyte and platelet counts are low. Each patient must be managed individually, according to the nature of malignant disease, general state of health and degree of immunosuppression. Antibiotic cover is important, and primary closure of the abscess cavity should never be attempted.


Resection of liver gastrinoma leading to persistent eugastrinemia. Case report.

In a 30-year-old man with Zollinger-Ellison syndrome, the only detectable gastrinoma was in the right liver lobe. Removal of the lobe, without additional gastric surgery, was followed by normalization of the gastrin level. Long-term follow-up confirmed the good result. The usefulness of quick intraoperative gastrin assay is stressed.


Septic pulmonary emboli after prolonged use of central venous catheter for parenteral nutrition. Case report.

A 48-year-old man underwent total parenteral nutrition via a central venous catheter because of small bowel obstruction after the reconstruction of the abdominal aorta. Three weeks after, he developed septic emboli in the right lung, which was one of rare complications of central venous catheter.


Eosinophilic gastroenteritis presenting as ascites. Case report.

A 46 year old man presented with a four week history of ascites and loss of weight. The diagnosis of eosinophilic gastroenteritis was made only after histological examination of a biopsy specimen taken at laparotomy. All other investigations had been unhelpful. He made a good recovery and was given no treatment.


Extragenital endometriosis. A review.

Extragenital endometriosis is common and may be found in any tissue. The most pronounced symptoms are pain and local bleeding that usually (at least initially) are cyclical and more pronounced at the time of menstruation. The lesions often infiltrate neighbouring organs, and cause considerable fibrosis together with increasing symptoms. The patients have often had pain for many years, have been investigated at different clinics, and been given conflicting diagnoses, often of mental instability, before the correct diagnosis is finally made. The disease is difficult to diagnose clinically, and must be verified histologically. Often the endometriosis responds to treatment with hormones to inactivate the ovaries, but, sometimes the lesions are resistant, or respond too slowly, to drugs, and local excision is required. A gynaecologist should be called if the diagnosis is made at laparotomy or laparoscopy, to establish the extension of the endometriotic lesion and should be consulted about complementary investigations and hormonal treatment.


Molecular determination of cell tropism of human immunodeficiency virus.

In the 10 years since AIDS was first identified, knowledge of the causative agent, human immunodeficiency virus (HIV), has advanced remarkably. Molecular biological analysis has had a greater impact on the investigation of HIV and AIDS than on that of any other disease. Unfortunately, the vast amount of material published on this subject has still not resulted in a thorough understanding of the pathogenesis of AIDS. Undoubtedly, part of the reason for the complexity of this disease stems from the ability of HIV to infect a large number of different cell types. To comprehend the mechanisms involved in the pathogenesis of AIDS, it is of great importance to understand the factors that control the cell tropism of the virus. In this review, we describe the known factors involved in the determination of the cell tropism of retroviruses and the ways by which molecular biological analysis of HIV has revealed the nature of the processes involved in control of the tropism of the virus for various cell types.


Peptic ulcer in cirrhotic patients: a short- and long-term study with antisecretory drugs.

The clinical course of gastric and duodenal ulcer and the efficacy of H2 blockers in ulcer healing and the prevention of relapse in cirrhotic liver patients were studied. Seventy-four cirrhotic patients with endoscopically proven acute gastric ulcer (30), duodenal ulcer (34) or a combination of both gastric and duodenal ulcers (10) were treated for six weeks with either Cimetidine 800 mg/daily (27) or Ranitidine 300 mg/daily (47). Of the 77 patients 49 (66.2%) were healed after therapy, 11 cases (14.8%) remained unhealed even after two additional cycles of the same treatment and four were lost to follow-up. After an endoscopically proven healing of the active ulcer, 51 patients took part in the long-term study over a mean period of 24 months: 21.5% of the 27 patients were treated with a maintenance dosage of H2 blockers and 29.1% of the 24 patients left without therapy relapsed during the first year. We conclude that the ulcer healing rate with H2 blockers is lower and the relapse rate higher in cirrhotic patients than in the general ulcer population.


Atypical affective disorder with episodic dyscontrol: a case of von Economo's disease (encephalitis lethargica).

The case is described of a patient with atypical affective disorder, episodic behavioural dyscontrol and parkinsonism resulting from presumed encephalitis lethargica. EEG abnormalities were found which were compatible with a post-encephalitic state and suggestive of epileptiform complications. Poor or deleterious response to neuroleptics, sleep disorder, and parkinsonism are features that may allow recognition of this illness in a psychiatric setting.


The cross-leg flap: still a useful flap in children.

Reconstruction of the distal lower limb and foot is a difficult problem, especially where large areas of skin loss have occurred. The cross-leg flap is a safe and reliable alternative to free tissue transfer in paediatric lower limb trauma. By incorporating fascia or muscle the versatility of the flap can be enhanced. Our experience with the cross-leg flap in children during the last 5 years is discussed.


Psychiatric emergency services in a Canadian city: II. Clinical characteristics and patients' disposition.

The clinical characteristics of patients seen at the psychiatric emergency facilities in a Canadian city and the determinants of decisions regarding their treatment were investigated. A total of 544 patients who sought psychiatric emergency services from the three hospitals in Saskatoon during a three month period were studied. Cognitive disturbance, past psychiatric history, previous psychiatric hospitalization and diagnoses of substance use disorders, affective disorders, anxiety disorders and schizophrenic disorders were associated with psychiatric emergencies. Psychiatric diagnoses and availability of social support were significantly associated with disposition. The implications of these findings for psychiatric emergency services are discussed.


Truncated fibronectin. An autologous growth-promoting substance secreted by renal carcinoma cells.

The human renal carcinoma cell (RCC) line ACHN proliferates in the absence of exogenous growth factors and secretes a 178-kilodalton growth-promoting substance (GPS). Complementary DNA (cDNA) was isolated that coded for polypeptides antigenically cross-reactive with GPS. Nucleotide sequencing of the cDNA showed strong homology with human fibronectin (FN). The deletion of an adenine in human FN codon 1482 caused a reading-frame shift that predicted early termination of translation after 1518 amino acid residues. Western immunoblotting human FN and GPS with anti-human FN antibodies showed that GPS was a truncated FN. Previous work found that malignant cells synthesized, bound, and deposited into the extracellular matrix decreased amounts of FN. Addition of this substance to transformed cells changed their morphology but not their rate of growth. By contrast, partial proteolysis of FN resulted in a prominent 180-kilodalton fragment that stimulated DNA synthesis. Similar to this finding, the authors showed that truncation of fibronectin during synthesis appeared to unmask latent DNA synthetic stimulating activity. Polymerase chain reaction methods using genomic DNA from normal kidneys and RCC and primers specific for the GPS-human FN gene showed two products of identical size, indicating that genomic amplification did not cause activation of the human FN gene in RCC to produce GPS. Restriction-fragment length analysis demonstrated identical patterns in DNA extracted from both normal kidneys and RCC, suggesting that chromosomal rearrangements did not activate the GPS-human FN gene. This study showed that genetic changes detectable only by DNA sequencing can explain the activation of the normal human FN gene to produce GPS, a product important for autologous growth stimulation of RCC.


Determination of biomarkers for intermediate end points in chemoprevention trials.

Renewed interest is being directed toward chemoprevention as a means of reducing cancer mortality. To overcome the inherent problems associated with using cancer development as a study end point, there has recently been a great surge of interest in defining the biomarkers associated with specific stages of the carcinogenic process as intermediate end points. We have detailed the evidence supporting the concept of field cancerization, a concept of general importance that is probably applicable to carcinogenesis and chemoprevention at many organ sites in humans, and presented results of tests of the potentially useful biomarkers proliferating cell nuclear antigen and blood group antigen. Because microassay techniques are more readily applicable to small biopsy samples, further expansion of these studies and exploration of panels of additional biomarkers are expected to generate exciting results in the field of chemoprevention.


Naproxen premedication reduces postoperative tubal ligation pain.

This study evaluated the effectiveness of naproxen sodium oral premedication in reducing postoperative pain, analgesic requirements and day surgery length of stay in patients undergoing outpatient laparoscopic tubal ligations. We undertook a randomized, double-blind clinical trial on ASA I and ASA II patients undergoing outpatient laparoscopic tubal ligations. The treatment group received two capsules containing naproxen sodium, 275 mg each, and the control group received two identical capsules containing placebo. Postoperative visual analogue pain scores, analgesic requirements, side-effects and length of day surgery stay were studied. Forty-four patients completed the study with 21 patients in the naproxen group and 23 in the placebo group. There was a statistically significant difference between groups in terms of pain score (naproxen group 0.9 +/- 0.2 vs placebo group 3.5 +/- 0.6); patients requiring postoperative opioids (naproxen group 0% vs placebo group 34.8%); and time spent in the day surgery unit (naproxen group 168 +/- 13 min vs placebo group 188 +/- 15 min). There was no difference in the incidence of nausea and vomiting. Only one person developed a side-effect from the naproxen sodium which was minor gastric discomfort. This study shows that naproxen decreased the postoperative tubal ligation pain with less subsequent postoperative analgesic requirements, less time to street fitness and no increase in analgesic side-effects. We recommend the use of this premedication in outpatient laparoscopic tubal ligations.


Half-life of exogenous growth hormone following suppression of endogenous growth hormone secretion with somatostatin in type I (insulin-dependent) diabetes mellitus.

To estimate the half-life of growth hormone in young adult patients with type I (insulin-dependent) diabetes mellitus following bolus injection and prolonged exposure for the purpose of deconvolution analysis of plasma growth hormone profiles to determine growth hormone secretory rates. In the bolus study, an intravenous bolus injection of 100 mU of biosynthetic human growth hormone was given while endogenous growth hormone was suppressed by a continuous infusion of somatostatin under three different glucose clamp conditions: normoglycaemia (5 mmol/l) with normoinsulinaemia (65 pmol/l); hyperglycaemia (12 mmol/l) with normoinsulinaemia; and normoglycaemia with hyperinsulinaemia (360 pmol/l). In the infusion study, the effect of prolonged and repeated growth hormone exposure upon the growth hormone half-life was estimated. Three pulses of 60 minutes growth hormone infusion (6 mU/kg/pulse) two hours apart under euglycaemic somatostatin suppression were applied. Six young adult patients with type I (insulin-dependent) diabetes mellitus were studied in both the bolus and the infusion study. Mean GH half-lives by mono-exponential analysis were not significantly different remaining unaltered by the short-term metabolic changes of hyperglycaemia and hyperinsulinaemia. Data were therefore pooled yielding an overall mean GH half-life of 13.6 minutes (range 11.9-19.4). Applying a bi-exponential model mean GH half-lives were 3.1 minutes (range 2.5-5.9) for the rapid phase of distribution of the hormone and 13.8 minutes (range 9.6-16.9) for the decay of GH from the circulation. The GH half-life during the infusions studies did not vary with repeated exposure but was significantly longer (mean half-life of 25.7 minutes; range 19.4-37.1) than during the bolus studies (P less than 0.001). The half-life of exogenous r-hGH is not affected by glucose or insulin concentrations but increases after prolonged GH exposure in young adults with type I (insulin-dependent) diabetes mellitus.


Carrier detection in X-linked ocular albinism of the Nettleship-Falls type by DNA analysis.

X-linked ocular albinism (XOA) is characterized by anomalies of the eyes and hypopigmentation or absence of pigment in skin, hair and eyes due to a hereditary inborn error of metabolism affecting the pigment cells. The gene of XOA of the Nettleship-Falls type (OA1) has been mapped to Xp22.3, and several closely linked RFLP loci have been identified. Linkage analysis and deletion mapping have established the marker gene order Xpter-STS-DX237-(OA1,DXS143,DXS85)-DXS1 6-DXS43-Xcen. Although the position of OA1 has yet not been fully resolved, we report on the first carrier detections in OXA of the Nettleship-Falls type by DNA analysis using markers which unquestionably flank OA1.


Influence of apolipoprotein B signal peptide insertion/deletion polymorphism on serum lipids and apolipoproteins in a Chinese population.

Insertion/deletion polymorphism of the apo B gene encoding signal peptide and its influence on serum lipids and apolipoproteins was studied in 269 Chinese of both sexes in Singapore. The frequency of the Del allele was found to be 0.20, which is significantly lower than that in Caucasians (France) (0.34). The distribution of genotypes of ins/del polymorphism was at Hardy-Weinberg equilibrium in this population. There was an excess of individuals with the deletion allele in hypercholesterolemic subjects compared to those with normal cholesterol levels (P less than 0.05). All the lipid and apolipoprotein values were regressed for age, sex and BMI by multiple regression analysis. Individuals with one or two del alleles had significantly higher levels of serum total cholesterol (248.8 +/- 13.0 and 255.4 +/- 20.4 mg/dl, respectively) compared to those in individuals with only the Ins allele (218.4 +/- 7.8 mg/dl) (P less than 0.05). Serum LDL cholesterol level was also significantly higher in individuals with del allele (173.4 +/- 11.7 mg/dl) compared to that in those without the del allele (141.1 +/- 7.4 mg/dl) (P = 0.02). The percentages of sample variance of different lipid traits explained by apo B signal peptide polymorphism were estimated by analysis of variance (ANOVA) with sex, age and BMI as covariates. 2.3% of variability of serum total cholesterol (F = 3.27, P = 0.040) and 2.8% of LDL cholesterol (F = 3.87, P = 0.023) could be explained by the ins/del polymorphism of the apo B signal peptide gene.