[Malignant histiocytosis associated with central neurological symptoms and cerebrospinal fluid involvement].

A 53-year-old woman was admitted with fever and general fatigue in December, 1988. A diagnosis of malignant histiocytosis (MH) was made based on her high level of LDH, thrombocytopenia, mild splenomegaly without systemic lymphadenopathy. There was also bone marrow infiltration large atypical cells and erythro-phagocytosis. VEPA therapy resulted in complete remission. Visual disturbance and left lagophthalmos were recognized in March 1990. These signs indicated central nervous system (CNS) relapse which disappeared after intrathecal methotrexate injection. The same symptoms and signs appeared after another, 5 months. Tumor cells were found not only in the central spinal fluid but also in bone marrow. CNS and bone marrow recurrence were treated with intrathecal methotrexate injection VEPA therapy and cranial irradiation. We diagnosed this case as MH, based on the clinical features which did not include systemic lymphadenopathy and laboratory findings although TcR-gamma rearrangement was observed in bone marrow cells. Only one case of CNS infiltration diagnosed when alive has previously been reported in Japan. We report here a very rare case in which by medical treatment CNS infiltrations was improved twice.


[A case of Paragonimiasis westermani with pleural effusion eight months after migrating subcutaneous induration of the abdominal wall].

Patients with Paragonimiasis westermani show a typical ring form or nodular shadow on chest X-ray, cough, sputum, and hemosputum. Recently, case reports of Paragonimiasis westermani, accompanied by pneumothorax and pleural effusion, as for Paragonimiasis miyazakii, have been increasing. Paragonimus westermani often causes an ectopic infection in various organs such as the peritoneal cavity, pleural cavity, pericardium, liver, adrenal gland and brain. Cutaneous paragonimiasis is considered one of the typical forms of ectopic infection in its earlier phase, but a few unexpected cases of cutaneous Paragonimiasis westermani have also been reported. A 68-year old man, who had never eaten fresh-water crab or raw sliced meat of wild boar, noticed subcutaneous induration of the abdominal wall. The induration had been gradually moving upwards and to the right from the infraumbilical region for over 20 days, and then disappeared at the right upper lateral abdominal wall. Eight months later, he developed severe pain in the right lower chest, and a chest X-ray showed right pleural effusion. Laboratory examinations revealed eosinophilia (WBC 3940/mm3, eosinophil 9%), elevated ESR, and an elevated serum total IgE level (5517 IU/ml). Ouchterlony's double diffusion test performed with the patient's serum in agarose showed strong bands toward Paragonimus westermani antigen, compared to Paragonimus miyazakii antigen. Immunoelectrophoresis with the patient's serum showed specific bands toward Paragonimus westermani antigen. This patient was finally diagnosed as having Paragonimiasis westermani infection, and he responded to praziquantel administration. The clinical course of this patient appears to be rare in cases of Paragonimiasis westermani infection. The clinical course of this case resembled some cases of Paragonimiasis miyazakii infection.(ABSTRACT TRUNCATED AT 250 WORDS)


[A case report of laparoscopic adrenalectomy].

Laparoscopic left adrenalectomy was performed on a 47 years old male patient with primary aldosteronism. Subcutaneous steel traction method was utilized in addition to intraperitoneal CO2 insufflation method. The combined use of steel traction method reduced CO2 insufflation pressure below 12 mmHg and might reduce possibility of CO2-related complications. A left adrenal gland was approached by a resection of phrenic colic ligament and a traction of a transverse and descending colon. Laparoscopic adrenalectomy has distinct advantages over open adrenalectomy in terms of avoidance of skin and muscle incision and rib resection, and early convalescence. This less invasive method might prevail in near future.


Global status of clinical photodynamic therapy: the registration process for a new therapy.

The clinical use of photodynamic therapy (PDT) has been ongoing for over a decade. However, attempts to apply for approval of the therapy from boards of health for general use began only in 1989. The unique nature of PDT and the resultant changes in the normal drug registration process, as well as steps which are being taken to approve PDT for the treatment of endobronchial lung cancer, superficial bladder cancer and esophageal cancer are described. The current clinical status of PDT in these indications is also reviewed.


Effect of 17 beta-oestradiol on lymphocyte subpopulations, delayed cutaneous hypersensitivity responses and mixed lymphocyte reactions in post-menopausal women.

High-dose steroids are known to be potent modulators of the immune response. We accordingly investigated the effect of therapeutic doses of 17 beta-oestradiol (E2) on cellular immune responses in post-menopausal women. Fifteen (15) healthy women who had undergone a natural menopause were treated with E2 in the form of 100 mg estraderm patches applied twice weekly for 3 out of every 4 weeks over a 3-month period, followed by combined oestrogen and progestogen formulations as long-term therapy. Blood samples were taken on two occasions prior to treatment and at weeks 1, 3, 4, 7, 9, 12 and 24 after commencing therapy. Lymphocyte subsets (CD2, CD4, CD8, CD19, HLA-DR and NK) were studied in each blood sample using a monoclonal antibody kit and a two-colour fluorescence flow-cytometer. One-way mixed lymphocyte reactions (MLRs) were performed using the same stimulator throughout. Delayed hypersensitivity skin tests (DHTs) were carried out twice before treatment and at weeks 3, 4, 12 and 24 using Multitest 7-antigen kits (Institut Mérieux). Lymphocyte subsets did not change significantly with treatment, but both the MLRs and the DHTs were significantly depressed, maximally so by the third week of treatment. We conclude that therapeutic doses of E2 modulate certain immune responses. The significance of this is discussed in the light of the increasing use of long-term oestrogen replacement therapy.


[Diseases of the kidneys and urinary tract and possibilities of their active detection in miners].

The examination of 630 miners aged 18-64 working in the mines of the Lugansk region revealed urinary and renal diseases in 15.7% of them. They were affected with chronic prostatitis (34.3%), urolithiasis (27.2%), chronic pyelonephritis (14.2%), 162 miners (33%) out of 490 had urinary shifts (hematuria in 91, proteinuria in 52, both hematuria and proteinuria in 19 examinees) when examined upon ascending from the mine. 61 miners had urinary syndrome only after working shifts. It was unrelated to relevant diseases. The authors point out the necessity of active screening of renal and urinary diseases during routine medical check-ups in miners.


[The creation of a laboratory culture of Anopheles martinius Schingarev, 1926].

A laboratory colony of Anopheles martinius has been first set up in the world. The starting colony was a sample of overwintered females collected in the Takhta-Kupyr district of Karakalpakia. The colony was reproducing in laboratory for 11 months (not less than 15 generations). The method for its maintenance is similar to that for An. sacharovi.


[Immediate allergic reaction to natural latex with special reference to surgical gloves].

There is an increasing incidence of contact urticaria (CU) and systemic reactions to rubber products. 34 patients are presented: Most were atopic (22/34) and women (29/34). 24 worked in the medical field. 13 patients showed signs of hand dermatitis. In 31 patients, rub and/or pricktests with liquid latex in different dilutions and with latex gloves led to positive reactions. The allergen(s) appear in part to be watersoluble: 23 of 31 patients revealed positive test reactions to an aqueous glove extract. In two patients, urticarial test reactions to TMTD, Mercapto-Mix, and PPD-mix were considered as possible contributing factor of CU. Scratch tests with corn-starch were negative in all patients. 17 of 29 sera showed RAST (radioallergosorbent test) class 0 using latex allergen disks. SDS-PAGE (sodiumdodecylsulfate-polyacrylamide-electrophoresis) determined protein bands of less than or equal to 14 kD (not allergen specific) and approximately 28 kD. The Western Blot detected the 28 kD protein as allergen in the sera of three patients. Isoelectric focusing (IEF) proved no protein bands. Immunoprinting performed with sera of five patients presented allergen bands in an pH range between 3.8 and 4.55. This shows that radiostaining (immunoprint) is more sensitive than the Coomassie Blue staining. Although three sera showed RAST class 0, immunoblotting detected allergen bands. In these cases the immunoblot appears to be more sensitive than the RAST. A cross reactivity between latex and banana could not be established. Alternative gloves are Neolon (neoprene) or Elastyren (styrene-butadiene polymer).


[The laboratory cultivation of Phlebotomus papatasi. The nature of the reaction of the sandflies to unfavorable environmental conditions].

The breeding of Phlebotomus papatasi in laboratory setting has been studied for 4 years. It has been found that in addition to the well-known factors such as temperature and humidity, sandfly development is affected by the features of reservoirs for their breeding, amount of nutrient substrate, duration of a diapause and developmental conditions of their parents. Ph. papatasi responds to deterioration of dwelling conditions with prolonged period of development, increased number of diapausing larvae and decreased number of emerged imagines, i.e. with development inhibition of different degree and movable transfer to diapause.


Structural and functional analysis of two cryptic plasmids from Lactobacillus pentosus MD353 and Lactobacillus plantarum ATCC 8014.

The DNA sequences of a 2.4 kb plasmid (p353-2) from Lactobacillus pentosus MD353 and a 1.9 kb plasmid (p8014-2) from Lactobacillus plantarum ATCC 8014 show 81.5% overall similarity. Both plasmids carry elements (replication protein gene, plus-origin and minus-origin of replication), which are typical of plasmids that replicate via a rolling-circle mechanism of replication (RCR). Direct evidence for an RCR mechanism was obtained by showing the accumulation of single-stranded plasmid intermediates in the presence of rifampicin. A minus-origin of replication was defined for plasmids p353-2 and p8014-2 based on DNA sequence analysis and on its ability to convert single-stranded into double-stranded plasmid DNA. Plasmids pLPE323, pLPE350 and pLPC37 that are derived from the p353-2 or p8014-2 replicon are structurally and segregationally stable in L. pentosus MD353, L. plantarum ATCC 8014 and in Lactobacillus casei ATCC 393. The presence of Escherichia coli or lambda DNA fragments in vectors derived from p353-2 or p8014-2 does not affect the structural stability but results in segregational instability of the vectors. The instability increases with increasing size of the inserted DNA fragment. Since vectors based on these replicons can be efficiently propagated in a wide variety of Lactobacillus species, they are highly suitable for cloning and expression of foreign DNA in Lactobacillus, provided that selective pressure is applied.


[The level of insecticide resistance in natural populations of houseflies].

The resistance to chlorophos and some pyrethroids (permethrin, fenvalerate and ethofenprox) were determined in house fly imagos from Moscow, some towns of the Moscow Province (Dmitrov, Kolomna, Zagorsk and others). Tajikistan, Turkmenia and also Czechoslovakia. The tested populations from the USSR were highly resistant to chlorophos (more than 100 times) and susceptible or tolerant to pyrethroids. Czechoslovak populations were more resistant to pyrethroids.


[The effect of socioeconomic and ecological conditions on tick-borne encephalitis morbidity in settled regions].

A relation between the tick-borne encephalitis morbidity, to the cattle-breeding methods and specific and quantitative structure of dairy cattle herds in developed regions is discussed. This relation is due to the fact that cows and goats are Ixodid hosts and donors of the virus. The factors like use of ameliorated pastures in cattle-breeding practice and cattle maintenance in the stalls deprive ticks of their hosts and donors of virus. It brings to decrease of vector density, valence of foci and human morbidity. On this basis, the prognosis of human morbidity in Byelorussia is given for the following decade.


Proteolysis of filament proteins in glial and neuronal cells after in vivo stimulation of hippocampal NMDA receptors.

An intrahippocampal injection of N-methyl-D-aspartate induced the appearance of degradation products of both the 68 kiloDalton neurofilament protein and the glial fibrillary acidic protein, as revealed by immunoblot techniques. The degradation of these two filament proteins was maximal at 10 days after the lesion. The degradation patterns were similar to those induced with calpains or calcium in vitro. There were no degradation effects on the 200 kD neurofilament protein as tested with both mono- and polyclonal antibodies. Consequently, the neuronal degeneration after excessive activation of NMDA receptors appears to involve calcium activation of proteolytic enzymes. The effects on the glial proteins are probably secondary to neuronal damage but could be related to calcium dependent processes.


[Nonparasitic hepatic cysts].

Serous cyst of the liver are a rare pathology which are often diagnosed during surgery. The paper reports 12 cases which were diagnosed during laparoscopy and discusses the etiopathogenesis of the disease, the latest diagnostic tools and the possible use of surgery. In conclusion, the Authors affirm that surgical laparoscopy represents an alternative form of treatment in some cases, such as polycystic liver.


[Decreased humoral immunity to the tick-borne encephalitis virus in the population of the western Urals].

A serological survey of the human population in the western Urals in 1966-1968 and repeated survey in 1988-1989, the decrease in humoral immunity to tick-borne encephalitis virus in all age groups of people was established in most of landscape subzones of the region. The most expressive decrease of humoral immunity was noted in middle-aged people living in the subzone of broad-leaved and coniferous forests and forest steppe.


[Seasonal variability in the insecticide resistance and irritability of Anopheles superpictus].

The resistance and irritability to malathion, fenitrothion, propoxur and DDT (WHO insecticide impregnated papers) in Anopheles superpictus from Dangara District were determined three times in season. Complete susceptibility to malathion, fenitrothion and DDT and low resistance to propoxur probably based on knockdown mechanism were noticed. DDT and malathion irritability levels were high, and those for fenitrothion and propoxur were lower. During the season irritability to malathion and fenitrothion (organophosphorous compounds) was slightly decreasing, and in contrast was increasing to propoxur (carbamate). Irritability to DDT (organochloride) considerably fell down in August and achieved the initial level in September again. None of the tested insecticides can be recommended for residual spraying in Dangara District because of high irritability levels in mosquitos or danger of its rapid increase after onset of spraying.


Role of serotonin receptor subtype in seizures kindled from the feline hippocampus.

This study assessed the effects of a serotonin (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and a 5-HT2 antagonist ketanserin on fully kindled seizures from the hippocampus. 8-OH-DPAT produced a marked suppression in hippocampal kindled seizures, while producing behavioral signs similar to those seen in the 5-HT syndrome. Although DOI and ketanserin did not affect kindled focal epileptic activity, DOI shortened and ketanserin prolonged the latency to onset of generalized convulsions. Our data suggest that 5-HT1A receptors play an inhibitory role in the generation of hippocampal seizures, whereas 5-HT2 receptors may participate in kindled seizure generalization from this region.


Pregnenolone sulfate augments NMDA receptor mediated increases in intracellular Ca2+ in cultured rat hippocampal neurons.

The ability of the neuroactive steroid pregnenolone sulfate to alter N-methyl-D-aspartate (NMDA) receptor-mediated elevations in intracellular Ca2+ ([Ca2+]i) was studied in cultured fetal rat hippocampal neurons using microspectrofluorimetry and the Ca2+ sensitive indicator fura-2. Pregnenolone sulfate (5-250 microM) caused a concentration-dependent and reversible potentiation of the rise (up to approximately 800%) in [Ca2+]i induced by NMDA. In contrast, the steroid failed to alter basal (unstimulated) [Ca2+]i or to modify the rise in [Ca2+]i that occurs when hippocampal neurons are depolarized by high K+ in the presence of the NMDA receptor antagonist CPP. These data suggest that the previously reported excitatory properties of pregnenolone sulfate may be due, in part, to an augmentation of the action of glutamic acid at the NMDA receptor.


Excitatory 5-HT2-mediated effects on rostral ventrolateral medullary neurones in rats.

Iontophoretic application of the 5-HT2 receptor agonist alpha-methyl-5-HT excited 41 neurones in the rostral ventrolateral medulla, including a population of barosensitive cells. At high ejecting currents (greater than 2-3 x threshold) the excitation was replaced by an inhibition. The excitatory responses evoked by low doses of alpha-methyl-5-HT were reduced during iontophoretic application of ketanserin (2-5 nA) in 8/9 cells. alpha-Methyl-5-HT inhibited ongoing activity of a further 28 cells. The inhibitions were not blocked by ketanserin (n = 3). We suggest that alpha-methyl-5-HT exerts an excitatory 5-HT2-mediated effect on neurones in the rostral ventrolateral medulla.


Treatment of iris melanoma with photodynamic therapy.

Photodynamic therapy was used to treat four patients with iris melanoma. Hematoporphyrin derivative was used as a sensitizing agent. The tumors were exposed to a total dose of 1.72 x 10(6) J/cm2 of 630-nanometer laser light. The eye of the first patient, enucleated after treatment, histopathologically showed significant tumor necrosis. The tumors in the three subsequent patients were almost completely ablated, with no evidence of regrowth.


The yeast homolog of the U1 snRNP protein 70K is encoded by the SNP1 gene.

The product of the yeast SNP1 gene has high homology to two domains of the metazoan U1 snRNP protein 70K, which binds to stem/loop I of the U1 RNA. However, the absence of other domains conserved in metazoan 70K and the minimal effect of yeast U1 RNA stem/loop I deletion make the assignment of SNP1 as yeast 70K less clear. To address this question, we have expressed the SNP1 gene as a fusion protein in E. coli and developed a gel shift assay for U1 RNA binding. We show here that the product of the yeast SNP1 gene binds directly and specifically to the first 47 nucleotides of yeast U1 RNA, which include the stem/loop 1 structure. We therefore conclude that the SNP1 gene product is the yeast 70K homolog. This is the first yeast protein to be identified as a homolog of a metazoan snRNP protein.


Cloning and sequence analysis of the StsI restriction-modification gene: presence of homology to FokI restriction-modification enzymes.

StsI endonuclease (R.StsI), a type IIs restriction endonuclease found in Streptococcus sanguis 54, recognizes the same sequence as FokI but cleaves at different positions. A DNA fragment that carried the genes for R.StsI and StsI methylase (M.StsI) was cloned from the chromosomal DNA of S.sanguis 54, and its nucleotide sequence was analyzed. The endonuclease gene was 1,806 bp long, corresponding to a protein of 602 amino acid residues (M(r) = 68,388), and the methylase gene was 1,959 bp long, corresponding to a protein of 653 amino acid residues (M(r) = 76,064). The assignment of the endonuclease gene was confirmed by analysis of the N-terminal amino acid sequence. Genes for the two proteins were in a tail-to-tail orientation, separated by a 131-nucleotide intercistronic region. The predicted amino acid sequences between the StsI system and the FokI system showed a 49% identity between the methylases and a 30% identity between the endonucleases. The sequence comparison of M.StsI with various methylases showed that the N-terminal half of M.StsI matches M.NIaIII, and the C-terminal half matches adenine methylases that recognize GATC and GATATC.


Requirements for U2 snRNP addition to yeast pre-mRNA.

The in vitro spliceosome assembly pathway is conserved between yeast and mammals as U1 and U2 snRNPs associate with the pre-mRNA prior to U5 and U4/U6 snRNPs. In yeast, U1 snRNP-pre-mRNA complexes are the first splicing complexes visualized on native gels, and association with U1 snRNP apparently commits pre-mRNA to the spliceosome assembly pathway. The current study addresses U2 snRNP addition to commitment complexes. We show that commitment complex formation is relatively slow and does not require ATP, whereas U2 snRNP adds to the U1 snRNP complexes in a reaction that is relatively fast and requires ATP or hydrolyzable ATP analogs. In vitro spliceosome assembly was assayed in extracts derived from strains containing several U1 sRNA mutations. The results were consistent with a critical role for U1 snRNP in early complex formation. A mutation that disrupts the base-pairing between the 5' end of U1 snRNA and the 5' splice site allows some U2 snRNP addition to bypass the ATP requirement, suggesting that ATP may be used to destabilize certain U1 snRNP:pre-mRNA interactions to allow subsequent U2 snRNP addition.


[Teicoplanin therapy in neonatal and pediatric intensive therapy].

We administered teicoplanin as specific antibiotic therapy for nosocomial "ICU specific" infections with methicillin-resistant Staphylococcus aureus and epidermidis (MRSA-MRSE). The above mentioned drug has been given to 20 patients (15 newborns and 5 not-newborns) admitted into intensive care unit during the years 1988, 1989, 1990 with MRSA-MRSE localized and/or systemic infection, affected by severe disease (RDS, pulmonary edema, congenital cardiac disease, cystic fibrosis) undergoing invasive procedures which presented high nosocomial infective risk (tracheal intubation, mechanical ventilation, venous and arterial cannulation, total parenteral nutrition, etc.). Complete recovery from systemic or localized infection (sepsis, low respiratory tract infection, high respiratory tract infection) occurred in 19 out of 20 patients, with a rate of success of 95%. Teicoplanin treatment lasted from a minimum of nine days to a maximum of thirty days. The dose was 5-6 mg/kg/die in one administration for the first three days, then 4 mg/kg/die. The tolerability of teicoplanin has proven satisfactory, since we had no major side effects during treatment and follow up.


[An association between anorectal malformations and Down's syndrome].

Down's syndrome is the most frequent chromosomal anomaly in humans and sometimes is associated with anorectal anomalies. The anorectal malformations include many varieties of anatomical anomalies, which are often difficult to evaluate. The Authors believe preoperative CT or MRI of the pelvis, together with other clinical and radiological examination to be a valid mean in the preoperative prognostic evaluation. In this study they analysed the association of anorectal malformations and Down's syndrome and the absence of a genito-urinary or perineal fistula.


[Cancer of the breast at the time of diagnosis. A national CANAM study: analysis of 3007 cases].

Between April 1988 and February 1990, 3,007 cases of female breast cancer were recorded among people insured by CANAM*; 118 cancers were bilateral from the start and 2,889 were unilateral. At the time of diagnosis the patients' age ranged from 24 to 101 years (median: 60 years), and 35.6 percent of the tumours were virtually subclinical. Lymph node involvement was clinically absent in 75 percent of the cases and histologically absent in 57 percent. In women under 50 the proportion of small TO-T1 tumours was greater than 40 percent, which pleaded for detection before the age of 50 years. Conversely, in economically weak populations and in women who were followed up for cancerous disease, breast cancer was diagnosed at a later stage. In older (retired) women (median age: 74), who accounted for 44 percent of the whole population, the proportion of advanced tumours was practically doubled (T4: 11 percent versus 6 percent), and the probability of metastases at the time of diagnosis had risen from 4.2 to 6.1 percent. In these patients, clinical examination once a year should contribute to an earlier diagnosis.


[Deep venous thromboses in erysipelas of the leg. A prospective study of 40 cases].

The treatment of lover limb erysipelas rests on antibiotic therapy directed against streptococci, but the necessity of prescribing a concomitant anticoagulant treatment has not yet been established. The incidence of deep vein thrombosis in patients with erysipelas of the leg in unknown. In a prospective study of 40 patients presenting with this type of skin disease, we looked for deep vein thrombosis, using systematically pulsed Doppler vein exploration combined with ultrasonography and, if necessary, a second Doppler examination and a phlebography. Six cases of deep vein thrombosis were diagnosed. This complication was observed in 5 patients at high risk for deep venous thrombosis; it had never been foreseen at clinical examination.


[Alveolar hemorrhage after cocaine inhalation].

Following inhalation of cocaine two young men developed haemoptysis associated with dyspnoea. One of these patients had severe clinical symptoms. There was blood eosinophilia, and haemosiderin was found in the macrophages that were present in the fibroscopic alveolar lavage fluid. X-ray films of the chest showed bilateral micronodular opacities. The outcome was favourable after treatment with parenteral dexamethasone, oxygen therapy and mask-administered continuous positive pressure ventilation. The frequency of cocaine-induced alveolar haemorrhage is probably underestimated; the condition must be suspected in subjects who inhale cocaine and have haemoptysis, no matter how small.


[Diabetic neuropathy. Difficulties of diagnosis and choice of tests].

None of the classifications of diabetic neuropathy already published is perfect. "Experts" now recommend an operational classification based on the quantification of signs and neurological deficits, on an electrophysiological investigation and on an easy exploration of autonomic neuropathy. Quantitative evaluation of symptoms can be performed with questionnaires or scales. Quantitative evaluation of deficits can be performed with devices which quantify vibratory and thermic sensations; reproducibility of the results is not yet perfect, but it represents a clear progress over clinical examination. Investigation of the autonomic control of cardiovascular system with standardized tests is the simplest way of exploring the vegetative nervous system; these tests have a fair sensitivity and an excellent reproducibility. Therapeutic trials, particularly with aldose reductase inhibitors or gangliosides, require this wide panel of neurological investigations.


Protein kinases in dentinogenesis.

Protein modifications such as phosphorylation and dephosphorylation are known to control several cell functions including regulation of the cell cycle, signal transduction and enzyme activation/inactivation. Bone and dentin contain highly phosphorylated anionic proteins that appear to be involved in the regulation of mineralization. This study was designed to identify and characterize the enzyme(s) responsible for phosphorylation (kinases) of dentin phosphoprotein (DPP) during dentinogenesis. DPP-protein kinase activity was demonstrated in a crude homogenate of dental pulp and odontoblast cells. In parallel studies, oligonucleotides to conserved amino acid sequences present in the active site of kinases were constructed and used to screen a lambda-gt11 tooth organ cDNA library. Several cDNA clones were isolated, the size of the insert determined by PCR (polymerase chain reaction) amplification, and in situ hybridization was used to determine cellular localization during tooth organ development. Preliminary evidence provides additional molecular determinants involved with candidate kinases responsible for DPP phosphorylation and dentinogenesis.


Morphological characterization of hypersensitive human radicular dentin and the effect of a light-curing resin liner on tubular occlusion.

A dentin biopsy technique was employed to compare the morphological features of hypersensitive and non-sensitive human radicular dentin. Specimens sampled from different areas in the same root surface displaying hypersensitivity or non-sensitivity were prepared for examination in the scanning electron microscope (SEM). Before analysis some specimens were exposed to surface demineralization and digestion of collagen to allow observation of subsurface portions of the dentinal tubules. In another set of observations the potential of a light-curing resin liner to penetrate root dentin in vitro and to maintain tubular occlusion over time following treatment of hypersensitive radicular dentin were examined. Orifices of many dentinal tubules were open in hypersensitive regions while non-sensitive areas generally displayed tubules occluded with mineralized material. SEM-images of HCl-collagenase treated specimens demonstrated the frequent presence of membrane-like structures in tubules of hypersensitive dentin. In non-sensitive dentin these structures were sparse. Topical application of a light-curing resin liner to wedge shaped defects prepared in radicular dentin of extracted human teeth resulted in a surface coating with a resin thickness of 20-50 microns. Resin penetrated dentinal tubules to a depth of more than 5 microns. Dentin biopsies examined 6 months after treatment with the liner showed presence of resin-like material in a majority of the tubules in dentin where hypersensitivity was no longer perceived. In none of the specimens did the liner remain as a surface coating. In areas of recurrent hypersensitivity more than half of the tubules presented with open orifices.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of a reduction in sodium intake on cold-induced elevation of blood pressure in the rat.

Chronic exposure of rats to cold (5 degrees C) induces hypertension within 3 weeks. The objective of this study was to determine the effect of treatment with graded levels of dietary NaCl on the induction of hypertension during chronic exposure to cold. Four groups of male rats were used. The first, given a commercial sodium-deficient diet containing 0.30% NaCl, served as the warm-adapted control group. The second, third, and fourth groups were given the same diet containing 0.075%, 0.15%, and 0.30% NaCl, respectively. Because cold-exposed rats ingest approximately twice as much food as warm-adapted controls, this represented half, the same, and twice the amount of NaCl ingested by the control group. The latter three groups were placed in cold air (5 degrees C). All cold-treated groups had an elevation of systolic blood pressure that was proportional to the concentration of NaCl in the diet by the seventeenth week of exposure to cold. Cardiac hypertrophy occurred to the same extent in all cold-exposed groups and was thus unaffected by the NaCl content of the diet or by the extent of elevation of blood pressure. Hence, cardiac hypertrophy during chronic exposure to cold is supported by other factors, possibly by the increased concentration of either norepinephrine or triiodothyronine, or both, which occurs characteristically in rats under these conditions. The results of this experiment suggest that the amount of NaCl ingested daily plays a role in the cold-induced elevation of blood pressure observed in rats.


ATP-dependent renal H+ translocation: regional localization, kinetic characteristics, and chloride dependence.

We characterized Mg(2+)-dependent ATPase activity in membranes from the renal cortex, the outer and inner stripes of the outer medulla, and papillary vesicles. In all regions, there was Mg(2+)-dependent ATPase activity that was resistant to oligomycin and vanadate and sensitive to N,N'-dicyclohexylcarbodiimide (DCCD), N-ethylmaleimide, and filipin. DCCD-Sensitive Mg(2+)-ATPase activity was highest in the inner stripe of the outer medulla and lowest in the cortex, with intermediate values in the outer stripe of the outer medulla and papilla. The Km for ATP, however, was similar among the different regions of the kidney. DCCD-Sensitive Mg(2+)-ATPase activity was critically dependent upon chloride with Km for Cl- in the range of 2-5 mM. In the presence of ATP, this ATPase was capable of H+ translocation, as assessed by acridine orange quenching. Inhibitors of ATPase activity prevented H+ translocation, which suggests that the Mg(2+)-ATPase represents, at least in part, an H(+)-ATPase. H+ transport was likewise critically dependent upon chloride, with similar Km. The effect of chloride on H+ translocation was blocked by the chloride channel inhibitor, diphenylamine-2 carboxylic acid. In the absence of chloride, H+ transport was abolished, but it could be partially restored by the creation of a favorable electric gradient by K+ and valinomycin. These studies demonstrate that the renal H(+)-ATPase exhibits different activities in various regions of the kidney. The ATPase activity and H+ translocation are critically dependent upon the presence of chloride, which suggests that chloride influences H+ translocation by dissipating the H+ gradient and acting at the catalytic site of the ATPase.


Effects of dietary essential fatty acid deficiency on the development of the rat thymus and immune system.

The paper describes an effect of essential fatty acid (EFA) deficiency on the development of the rat thymus and pups' immune system. From birth until being weaned (22nd day), the pups were hand-fed artificial milk diets containing a low (EFA-D) or high (EFA-R) proportion of EFA in the lipid fraction. The weight parameters of the body, thymus and spleen, the fatty acid composition of the individual thymus phospholipid subclasses, and mitogen-induced proliferation of thymus and spleen lymphocytes were studied. The results show that the total body weight of the EFA-deficient (EFA-D) fed animals was significantly decreased in comparison with the EFA-rich (EFA-R) and rat milk hand-fed animals. For the EFA-D group of young rats a high level of the (n-9) and (n-7) series fatty acids [mainly oleic 18:1(n-9) and eicosatrienoic 20:3(n-9) acids] was characteristic of the fatty acids in phosphatidylcholine and phosphatidylethanolamine in the thymus, compensating for the reduction of the content of arachidonic acid 20:4(n-6). The biochemical index of the EFA nutritional deficit in the thymus tissue was observable as early as on day 7. The mitogen-induced (Con A) proliferation of the thymus and spleen lymphocytes was decreased both on the 30th and 40th day of life. The results show that the EFA nutritional deficit in the early postnatal period caused damage to the structure of thymus in the young rats, most probably as a result of the change in the composition of the lipid fraction. These changes also affected the development of the immune system of the whole organism.


Pharmacokinetics of omega-3-fatty acids during ingestion of fish oil preparations.

An in vivo comparison of three dosages (3 g, 6 g, 12 g) of two different fish oil preparations in terms of plasma concentrations of their major active components eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was performed. The plasma accumulation was measured during 28 days of ingestion and an equally long wash out period. Data were scrutinized for bioavailability in order to distinguish between the efficiency of the two preparations. Rapid increases in EPA and DHA plasma concentrations can be demonstrated at all dosages during a 28-day ingestion period. EPA accumulated more during ingestion of high than of low dosages of fish oil. DHA revealed almost identical increases and peak values in plasma concentrations in all subgroups. The present data demonstrate dose dependent increases of EPA concentrations whereas DHA plasma concentrations are comparable in all dosages investigated. Measurable EPA and DHA plasma concentration levels are inappropriate means to explain clinical effectiveness. These results were found in both commercially available fish oil preparations. Direct comparison of both preparations revealed no differences in bioavailability.


DNA as a solar dosimeter in the ocean.

Stratospheric ozone depletion may result in increased solar UV-B radiation to the ocean's upper layers and may cause deleterious effects on marine organisms. The primary UV-B damage induced in biological systems is to DNA. While physical measurements of solar UV-B penetration into the sea have been made, the effective depth and magnitude of actual DNA damage have not been determined. In the experiments reported here, UV-B-induced photoproducts (cyclobutane pyrimidine dimers) have been quantified in DNA molecules exposed to solar UV at the surface and at various depths in clear, tropical marine waters off Lee Stocking Island (23 degrees 45' N, 76 degrees 0.7' W), Exuma Cays, Bahamas. (14C)thymidine-labeled DNA or unlabeled bacteriophage phi X174 DNA was placed in specially designed quartz tubes at various depths for up to five days. Following exposure, DNA samples were removed to the laboratory where UV-B-induced pyrimidine dimers were quantified using a radiochromatographic assay, and bacteriophage DNA inactivation by solar UV-B was assayed by plaque formation in spheroplasts of Escherichia coli. Pyrimidine dimer induction was linear with time but the accumulation of dimers in DNA with time varied greatly with depth. Attenuation of dimer formation with depth of water was exponential. DNA at 3 m depth had only 17% of the pyrimidine dimers found at the surface. Bacteriophage phi X174 DNA, while reduced 96% in plaque-forming ability by a one day exposure to solar UV at the surface of the water, showed no effect on plaque formation after a similar exposure at 3 m. The data collected at the water's surface showed a "surface-enhanced dose" in that DNA damages at the real surface were greater than at the imaginary surface, which was obtained by extrapolating the data at depth to the surface. These results show the sensitivity of both the biochemical (dimers) and biological (phage plaques) DNA dosimeters. DNA dosimeters offer a sensitive, convenient and relatively inexpensive monitoring system, having both biochemical and biological endpoints for monitoring the biologically effective UV-B flux in the marine environment. Unlike physical dosimeters, DNA dosimeters do not have to be adjusted for biological effectiveness since they are sensitive only to DNA-mediated biologically effective UV-B radiation. Results of pyrimidine dimer induction in DNA by solar UV accurately predicted UV doses to the phage DNA.


Parental and family well-being in families of children with Down syndrome: a comparative study.

The purpose of this study was to examine the effects of a child with Down syndrome on the individual functioning of both parents, marital functioning, and family functioning. Thirty-four families of children with Down syndrome were compared to 41 families with nondisabled children. Mothers and fathers in both groups completed a series of self-report measures. No significant differences were obtained between the two groups of families on any of the measures of individual, marital, or family functioning. The results of this study support a competence model in which parents may respond to the challenges associated with parenting a child with Down syndrome with resilience and adaptive functioning.


Mechanisms and amelioration of acute renal allograft failure in the cyclosporine era.

The fairly wide-ranging spectrum of tactics under investigation for ameliorating acute renal allograft dysfunction caused by harvest/preservation-related ischemia, acute CsA nephrotoxicity, and acute immunologic crises reflect the fact that no single approach has emerged as universally useful for mitigating the vasomotor nephropathy produced by the combined effects of each of these vectors of vasomotor renal allograft injury. Given the clinical heterogeneity of patients and allografts, it is the author's bias that, in addition to careful donor and recipient hemodynamic management, induction immunosuppressive regimens should be individualized on the basis of allograft function in the immediate postreperfusion period (judged by rate of diuresis, intraoperative parenchymal tone, renal scan profiles, and rate of decline of serum creatinine concentration) as well as patient-specific immunologic and general medical risk factors. Promising laboratory and clinical investigations of such agents as calcium channel blockers, substances promoting intrarenal vasodilator vs. vasoconstrictor prostaglandin formation, and atriopeptins have the potential to provide clinically helpful options with regard to adjunctive therapy for ameliorating acute renal allograft dysfunction associated with INF and ACR.


The HOME inventory: a new scale for families of pre- and early adolescent children with disabilities.

A preliminary form of a new version of the Home Observation for Measurement of the Environment (HOME) is presented. It is designed for use with families of children aged 10-15. The 80-item preliminary version of the Preadolescent HOME (PA-HOME) was field tested on 117 children with varying disabilities. The 80 items were selected from a pool of over 250 items by means of several field tests and accompanying item analyses. Both factor analyses and item analyses were used to help pare down items and produce a scale with acceptable psychometric properties. The psychometric properties of the PA-HOME are quite similar to those reported for the other three versions of the HOME Inventory. It appears to be a reasonably reliable scale with moderate correlations with other measures of the family environment, such as SES, social support, and marital stability. It has low to moderate correlations with measures of child competence in this sample of children with disabilities. The correlations are of the same general magnitude of correlations between the Infant-Toddler, Early Childhood, and Middle Childhood versions of HOME in samples of younger children with disabilities.


[Epidemiology of asthma in children and young adults in Algiers].

A sampling survey was carried out in Algiers among households to assess the frequency of chronic asthma in children and young people and to investigate the handicap resulting from this disease. 4,677 subjects younger than 25 years of age were registered, 47% of whom were children under 15. A report by households of a doctor's diagnosis of asthma was used to identify subjects with this disease from a direct face-to-face interviewing. The overall annual prevalence was 34.2 per thousand and the annual incidence was estimated as 3.1 per thousand. Except for children under 5 years of age which prevalence was 16 per thousand, the prevalence ranged from 34 to 41 per thousand for the other age groups. There was no significant difference between children and young adults for prevalence or incidence rates of asthma. The prevalence was two times greater in boys than in girls. On the other hand, the prevalence of asthma was 2.5 times greater in upper social class persons than in lower class persons. The proportion of severe handicaps was very low. But moderate handicaps resulting from asthma especially in the field of occupation were substantially frequent, 21% of asthmatics had a curtailed or adjusted occupation.


The coagulative system in haemodialyzed patients: the relationship between the elderly and hypertrygliceridaemia.

The coagulative system has an important role on haemodialysis and on atherosclerosis genesis; in particular the platelets are key elements of the coagulation and of atherosclerosis phenomena. Alterations of the coagulative system and increase risk of developing atherosclerosis are reported in the aging. We in this paper, report the results obtained studying the influence of the interaction between the elderly and dyslipidemia on the coagulative system in haemodialyzed patients. The obtained data showed that the hypertriglyceridaemia in interaction with the elderly accelerates and increases platelet aggregation after stimulation by ADP, Epinephrine and Collagen. So, it is important to consider hypertriglyceridaemia and age as thrombogenic factors and atherosclerosis accelerating factors in haemodialyzed patients.


[Interventional radiology in the treatment of acute and chronic mesenteric ischemia].

Radiologic revascularization procedures--i.e., percutaneous transluminal angioplasty (PTA) and fibrinolysis--are a valuable alternative to surgery in the treatment of stenoses and occlusions of the visceral vessels, that is the celiac tripod and the superior and inferior mesenteric arteries. We treated 32 patients, 10 of them with acute mesenteric ischemia and 22 with chronic mesenteric ischemia and clinical signs of angina abdominis. Grüntzig or pre-shaped Cobra or Simmons balloons were employed (diameter: 5-7 mm, with variable length) when PTA was performed. Urokinase or rtPA was employed for fibrinolysis. In 3 cases acute mesenteric ischemia was not occlusive and could be successfully treated with papaverine infusion. In 7 cases, acute mesenteric ischemia was occlusive: in 5 of these patients it was successfully treated by PTA and/or fibrinolysis. Our results were positive in 80% of the cases, with remission of clinical signs in 4 of 5 patients treated for acute mesenteric ischemia. In 22 patients with chronic mesenteric ischemia, 26 stenotic occlusions were observed at angiography and 22 were treated with PTA, which was technically successful in 21 instances (early success rate: 85-95%). At 24 months, 10% of restenosis was observed. In our experience, PTA of the visceral district, possibly preceded by loco-regional infusion of fibrinolytic drugs, can be widely applied and yields excellent therapeutic results.


Pharmacology and preclinical antiemetic properties of ondansetron.

Ondansetron (GR 38032) has potent and highly selective antagonist properties at the 5-hydroxytryptamine (5-HT, serotonin) 5-HT3 receptor. The selectivity ratio for ondansetron on 5-HT3 receptors compared with actions on other neurotransmitter receptor types is greater than 1,000. The antiemetic properties of ondansetron have been determined in ferrets against the nausea and vomiting induced by cisplatin, cyclophosphamide, and whole-body radiation. Ondansetron (intravenous 0.01 to 0.1 mg/kg or subcutaneous 0.1 to 0.5 mg/kg) or metoclopramide (1.0 to 4.0 mg/kg) cause dose-dependent inhibitions of the vomiting induced by each of these procedures. Unlike ondansetron, the effects of metoclopramide are accompanied by moderate to marked behavioral depression. Since metoclopramide is 50 times more potent on dopamine D2 receptors than on 5-HT3 receptors, the behavioral depression is likely due to profound blockade of dopamine receptors. The 5-HT3 receptors have been shown to be present peripherally on vagal afferent fibers and are densely located in the vomiting center of the hindbrain. The current hypothesis is that there may be both a peripheral and a central site of action for ondansetron and other 5-HT3 antagonists. The lack of antagonist activity on dopamine and other non-5-HT3 receptors indicates that, unlike metoclopramide, ondansetron will not cause extrapyramidal or other dose-limiting side effects.


Phase I and other dose-ranging studies of ondansetron.

Phase I studies of intravenous (IV) ondansetron in cancer patients receiving emetogenic chemotherapy were designed to assess the degree of antiemetic protection and pattern of adverse events produced by ondansetron at various doses. In a study of 44 patients receiving various forms of chemotherapy (including cisplatin), ondansetron was administered in three IV doses 2 hours apart beginning 30 minutes prior to chemotherapy. Antiemetic efficacy was seen at all dose levels (0.04 mg/kg to 0.35 mg/kg), with 54% of patients experiencing no vomiting and 76% experiencing two or fewer vomiting episodes within the first 24 hours. Overall, ondansetron was well tolerated, and no dose-limiting toxicity was observed. The most common adverse events were mild sedation, mild headache, and transient elevations of transaminases. In a second phase I study, 45 patients receiving cisplatin (median dose 100 mg/m2) were given ondansetron in three IV doses (range, 0.01 mg/kg to 0.48 mg/kg) 4 hours apart. There was no statistically significant difference in antiemetic efficacy among dose levels from 0.06 mg/kg to 0.48 mg/kg; however, there was a trend toward a decrease in the number of patients with failure of antiemetic protection at the higher exposures. Overall, 44% of patients had no emetic episodes, and 81% of patients had two or fewer emetic episodes within the first 24 hours. The number and intensity of adverse events, of which headache was the most common, appeared to increase at the 0.48 mg/kg dose level. A randomized double-blind study that compared three dose levels of ondansetron indicated that three doses of 0.15 mg/kg was superior in efficacy to three doses of 0.015 mg/kg, and not significantly different from three doses of 0.30 mg/kg. Dystonic reactions or akathisia were not noted in any study.


Phase II trials of ondansetron with high-dose cisplatin.

Phase II trials of ondansetron were undertaken to assess the ability of this agent to control nausea and vomiting caused by specific chemotherapeutic agents, to establish the optimal number of doses and the most appropriate schedule of administration, to see if control could be improved by the use of continuous infusion, and to ascertain if the degree of efficacy and safety of ondansetron would warrant further investigations. In each of six multiplebolus trials, ondansetron was given at 0.15 mg/kg to 0.18 mg/kg intravenously for three doses, beginning 30 minutes prior to cisplatin. No patient had received prior cancer chemotherapy. Overall, 48% of patients experienced no emesis, and 71% had zero to two emetic episodes after receiving cisplatin doses of 100 mg/m2 or greater. Comparable antiemetic control was seen with all schedules studied. Three additional trials assessed the effect of the number of doses of ondansetron on antiemetic effectiveness. A single dose gave complete protection in 25% of patients and three doses gave a 50% no-emesis rate. Complete control was not improved when six doses of ondansetron were given. Efficacy rates with multiple-bolus therapy and continuous infusion over 24 hours were similar. Side effects were mild and reversible in all trials, and there were no remarkable differences in adverse events among different schedules or numbers of doses. The complete and major control rates observed show that ondansetron is as effective as or more effective than metoclopramide in controlling cisplatin-induced emesis.


Comparative trials of ondansetron versus metoclopramide in the prevention of acute cisplatin-induced emesis.

A logical outgrowth of the early clinical success with ondansetron in phase I and phase II trials has been an interest in comparative antiemetic trials using conventional agents. Metoclopramide is generally acknowledged to be the single most effective conventional drug for the prevention of acute cisplatin-induced emesis and, therefore, was considered an appropriate agent for inclusion in comparative trials with ondansetron. Three phase III trials comparing metoclopramide with ondansetron for the prevention of acute nausea and vomiting associated with cisplatin administration have been completed to date. One was a single-blind, parallel-group trial conducted in the United States, and the other two were double-blind, crossover trials performed in Europe. The efficacy results of these studies demonstrated either a consistent trend or clear superiority of ondansetron in comparison with metoclopramide. Treatment failure consistently developed much later with ondansetron than with metoclopramide. Less antiemetic toxicity was noted with ondansetron. With the exception of headache, there was a lower incidence of neurologic adverse events in the ondansetron group. No dystonic reactions were observed with ondansetron in any of the trials. In all three trials, patients expressed greater overall satisfaction with ondansetron for emesis control.


Antiemetic activity of ondansetron in cancer patients receiving non-cisplatin chemotherapy.

The emetogenic properties of chemotherapeutic agents differ in terms of the frequency, intensity, time of onset, and duration of vomiting and nausea. As the effects of antiemetic agents in the control of emesis induced by different chemotherapeutic agents could differ, new antiemetics must be tested against a variety of chemotherapy challenges. In many non-cisplatin chemotherapy situations, a partly or totally oral schedule of antiemetic administration may be preferable. The selective 5-hydroxytryptamine (5-HT3)-receptor antagonist, ondansetron, has been shown to be a safe, effective, and well-tolerated antiemetic in the prevention of nausea and vomiting from several non-cisplatin chemotherapies. In randomized studies, ondansetron has compared favorably with metoclopramide in patients receiving cyclophosphamide-containing chemotherapy regimens.


The use of ondansetron in patients receiving multiple-day cisplatin regimens.

The control of nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy has remained difficult, even with the use of combination antiemetic regimens containing metoclopramide. Although these patients receive a lower daily dose of cisplatin, the emetogenic potential remains high. In addition, many of the patients receiving multiple-day cisplatin regimens are young (eg, testicular cancer patients) and, therefore, have particular problems with the extrapyramidal side effects associated with metoclopramide. Studies show that ondansetron, used as a single antiemetic agent, is effective, safe, and well tolerated in the control of nausea and vomiting in patients receiving multiple-day cisplatin regimens.


Toxicity and side effects of ondansetron.

The safety of ondansetron has been carefully evaluated through laboratory studies and clinical trials. Preclinical studies demonstrated that there is no end-organ toxicity in rats and dogs administered ondansetron doses 30 to 100 times those used in humans. At near-lethal doses of ondansetron, animals developed subdued activity, ataxia, and convulsions. Modest transient increases in serum transaminase values were observed. Concurrent administration of ondansetron with chemotherapy had no effect on tumor response in animals. The clinical safety of ondansetron has been evaluated in more than 2,500 cancer patients who received intravenous doses as large as 1.5 mg/kg. In adult patients receiving single-day chemotherapy, the incidence of adverse events was 36% with ondansetron (n = 647) and 50% with metoclopramide (n = 498). Diarrhea occurred in 9% of ondansetron patients and 19% of metoclopramide patients. Headache occurred in 14% of ondansetron patients and 8% of metoclopramide patients. Extra-pyramidal symptoms were reported in none of the ondansetron patients and 5% of the metoclopramide patients. The incidence of vascular occlusive events and seizure disorders was nearly identical with ondansetron and metoclopramide and similar to the cancer population in general. In a group of 209 pediatric patients receiving chemotherapy, the incidence of adverse events was 19% with ondansetron. Serum transaminase values increased significantly in 6% to 8% of ondansetron patients and 2% of metoclopramide patients. There was no apparent relationship between the cumulative dose of ondansetron administered and the incidence of increased transaminase values. However, there was an apparent relationship between the cumulative dose of cisplatin administered and the incidence of transaminase abnormalities. These data demonstrate that ondansetron is better tolerated than metoclopramide and is safe for intravenous administration to pediatric and adult patients receiving chemotherapy.


Rationale for combination antiemetic therapy and strategies for the use of ondansetron in combinations.

The identification of several safe and effective agents for the control of chemotherapy-induced nausea and vomiting has prompted an intensive effort to develop combination antiemetic regimens. The principal rationale for development of drug combinations is the potential for blocking different types of neurotransmittor receptors controlling the emetic process. Studies have shown that the combination of a neurotransmitter receptor blocker, a corticosteroid, and a benzodiazepine improves antiemetic efficacy, lessens side effects, and decreases the length of treatment and the number of drug administrations. Ondansetron appears to be an excellent antiemetic for use in combination programs because of its highly selective, 5-hydroxytryptamine (5-HT3)-blocking properties and its proven single-agent effectiveness and safety. Preliminary data show that ondansetron can be combined with dexamethasone safely with enhanced antiemetic results. Ondansetron merits further study in combination antiemetic programs.


The delayed-emesis syndrome from cisplatin: phase III evaluation of ondansetron versus placebo.

Cisplatin may evoke both an acute emetic response during the first 24 hours following treatment and a less well-recognized syndrome of delayed emesis. While delayed emesis is usually less severe in terms of frequency of vomiting episodes, the problem continues to result in significant morbidity. In comparison with acute emesis, the exact pathogenesis of the delayed emesis syndrome remains unclear. Although a combination of oral metoclopramide and dexamethasone is effective in many patients in preventing delayed emesis, almost 50% continue to experience at least one emetic episode when treated with this regimen. A phase III multicenter study has evaluated oral ondansetron versus placebo in the prevention of the delayed-emesis syndrome in 50 patients during days 2 through 5 following high-dose cisplatin administration. Although the daily rates of complete emetic control, failure, and control of nausea favor ondansetron, this trial is statistically inconclusive in establishing efficacy of ondansetron as a single agent in the prevention of delayed emesis. Ondansetron was well tolerated in the dose and schedule used.


Ondansetron metabolism and pharmacokinetics.

Hepatic oxidative metabolism accounts for more than 95% of ondansetron clearance from the body. The major excreted metabolites are conjugates of 7-hydroxy or 8-hydroxyondansetron, which appear to contribute little to the activity of the parent drug. Ondansetron plasma clearance averages approximately 0.45 L/h/kg, is similar in young male volunteers and cancer patients undergoing cisplatin-based chemotherapy, and does not change significantly with repeated dosing. Clearance decreases with increasing age, whereas volume of distribution remains unchanged. The result is an increase in mean plasma half-life from 3.5 hours in young volunteers (18-40 years) to 5.5 hours in volunteers over 75 years of age. Clearance and volume of distribution are higher in young (7-12 years) cancer patients, resulting in a mean plasma half-life of 2.5 hours. Plasma clearance is slightly slower in females. Ondansetron clearance decreases and half-life increases in patients with severe hepatic insufficiency. Clearance may be enhanced in patients receiving known hepatic enzyme inducers. Because of large intersubject variability in clearance and the relative safety of ondansetron, adjustments in ondansetron dosing based on age or gender alone are not recommended. Ondansetron is rapidly and completely absorbed when administered as a tablet. A relationship exists between control of emesis and the area under the plasma concentration-time curve for ondansetron. All data collected to date support the thesis that ondansetron is a competitive antagonist of the 5-hydroxytryptamine (5-HT3) receptor in humans.


Socio-economic circumstances and functional abilities of elderly black persons in the Orange Free State.

A community-based epidemiological study was undertaken to determine the health profile of the elderly black population in the Orange Free State. Four hundred elderly blacks were randomly selected from 10 towns. Questionnaires on past and present illnesses, socio-economic circumstances (including formal education) and daily activities were completed. Most of the elderly blacks received a state old-age pension and 15.3% were still economically active. We found that 63% of the subjects were illiterate and that 31% did not live with their children. Inability to perform any of six activities was found in 3.2%. In view of the high number of elderly persons living alone, we feel that the development of support services should receive urgent attention.


[The incidence of ischemic heart disease and its risk factors in 20- to 54-year-old male workers in physical and intellectual jobs].

The low incidence of coronary heart disease (CHD) was established in the course of a one-stage epidemiological examination of 2562 men aged 20-54 years (a random sample from an open city population). It was found to be associated with an insignificant prevalence of lipid metabolism abnormalities (excluding hypoalphacholesterolemia) and did not depend on the nature of labour (4.3% among white collars and 4.4% among blue collars). The incidence of overweight and high AP turned out approximately identical, whereas tobacco-smoking, hypercholesterolemia and hypertriglyceridemia were mostly recorded in blue collars. The prevalence of CHD and its risk factors increased with age, excluding tobacco-smoking. In the latter case, it reduced with age.


[The role of a lesion of the gastrointestinal tract in the origin of urticaria].

The relations between urticaria and various diseases of the gastrointestinal tract (GIT) are under discussion. The disturbances of the gall bladder and biliary vessels, liver diseases, and disorders of the stomach are most often among those diseases. The main role is played by disturbances of upper GIT motility, bacterial and viral infection. It is necessary that in the treatment of GIT lesions-related urticaria, disturbances of the GIT may be corrected.


Monoclonal antibody-based enzyme-linked immunosorbent assays (ELISA) for the measurement of vitamin K-dependent protein S: the effect of antibody immunoreactivity on plasma protein S antigen determinations.

Two monoclonal antibodies (Mabs) specifically directed to human protein S (PS) - named 5E9E9 and 3B10.25 - were produced and their properties compared to those of 2 previously characterized anti-PS-Mabs (HPS-2 and S10). 3B10.25, similar to S10, was directed to the calcium-free conformation of PS and had virtually identical affinity for free and C4b-binding protein (C4b-BP)-bound PS; 5E9E9 similar to HPS-2, had no calcium-dependency and was selectively directed to free PS. All Mabs were equally reactive to freshly purified and thrombin-cleaved PS. To evaluate the influence of C4b-BP bound PS on PS antigen determinations, ELISA systems employing the four Mabs individually as capture antibody (Ab) and peroxidase-conjugated polyclonal anti-PS IgG as detecting Ab were developed and compared to immunoelectrophoresis (EIA) and to an ELISA employing polyclonal anti-PS IgG as capture and detecting Ab, in the determination of PS in purified systems and in plasma. With all the ELISAs there was parallelism of dilution curves obtained with normal plasma and purified PS; however, supplementation of plasma with purified C4b-BP resulted in loss of parallelism when employing the Mabs directed to free PS as capture Ab. Influence of high C4b-BP on PS antigen determinations was confirmed in a series of plasma samples from patients with C4b-BP levels ranging from 70% to over 200%. Compared to the values obtained with the S10- or 3B10.25 - based ELISAs - which were similar despite a 10-fold difference in sample dilution - plasma PS was underestimated by the ELISAs employing 5E9E9 or HPS-2 while it was overestimated by EIA.(ABSTRACT TRUNCATED AT 250 WORDS)


Release of thromboxane A2 and beta-thromboglobulin during in-vivo plug formation following standardized skin incisions: effect of a moderate fish intake.

This paper describes a controlled study of the effects of a fish supplement on haemostasis. This was evaluated by measuring bleeding times from skin incisions, the volume of the emerging blood, the number of platelets taking part in the formation of the haemostatic plug (platelet retention), and the release of thromboxane B2 and beta-thromboglobulin in volunteers, before and after consuming a daily supplement of 100 g of fish (n = 20) or meat (n = 20) paste for 6 weeks. The fish supplement decreased the amount of thromboxane B2 released per platelet incorporated into the plug. Despite this, the skin bleeding times were hardly changed. There was also no difference in platelet retention, which was consistent with there being no difference in the release of beta-thromboglobulin. These results suggest that in the effect of marine diets on haemostasis, a reduced vascular reactivity plays a more important role than decreased plug formation.


[Laparoscopic closure and tegmentation of perforated ulcer].

Laparoscopy is fully recognized for diagnosis and even treatment of various acute abdominal conditions. In a 42-year-old woman with intense lower abdominal pain, laparoscopy revealed a perforated peptic ulcer. The ulcer was closed and patched with omentum and the abdomen was irrigated, all by laparoscopic techniques. Except for a minor wound infection recovery was uneventful.


[Handling and decisions by the authorities of reported occupational tendon injuries of the upper extremities. Occupational diseases' registry E6b].

The aim of this investigation was to show how the Danish National Social Security Office, (the department of industrial injuries insurance (NSS)), handles the cases and makes the final decisions concerning the diseases in tendons in the upper extremity belonging to the list of occupational disorders in the Danish Workers' Compensation Act. Five hundred and nineteen notified cases were followed-up until the final solution and eventual compensation for permanent injury and loss of earning capacity. Two hundred and twenty-six cases had to be excluded because the criteria in the list of Occupational Disorders concerning unusual work and complete or partial inability to work were not fulfilled. Sixty-seven commenced work again after the notification and forty four did not reply to the NSS correspondence. One hundred twenty-seven had to be eliminated for other reasons. Fifty-five cases could be further investigated according to the workload criteria. fourteen were accepted and forty-one were rejected. Eight of these were paid a total compensation for permanent injuries amounting to 200,000 DDK and a capitalized compensation for loss of earning capacity amounting to 1,000,000 DDK. The notified diseases occurred among unskilled workers in their forties, equally frequently in men and women. It takes a long time to obtain the answers to NSS correspondence from doctors as well as the injured persons and therefore a total handling time of up to one year has to be expected. Our conclusion is that it is difficult to have these diseases accepted as being caused by the work because the criteria on the list about "unusual work" and "complete or partial inability to do normal work" exclude many cases from acceptance. Probably the criteria for workload should be changed so that it is based on an objective goal for the workload and the movements to a greater extent compared with the exposure time. Doctors who report the diseases should be more precise in the notified diagnosis, symptoms and the workload responsible.


[Hypercalcemia during immobilization and prolonged anuria treated with disodium clodronate].

Severe hypercalcaemia was observed during prolonged anuria and prolonged immobilization in a previously healthy 34 years old male after a severe trauma caused by a traffic accident. Other causes of the hypercalcaemia were evaluated, and even though granulomas of unidentified nature were found in the liver after partial resection due to traumatic rupture the immobile state was concluded to be the major cause. A maximum calcium value of 4.44 mmol/l was seen after 10 weeks immobilization. The patient was treated with daily dialysis and, even though the calcium content in the dialysis fluid was reduced, only a minor effect was seen on the calcium level. After eight weeks of hypercalcaemia, the patient was treated with disodium clodronate intravenously 400 mg for daily five days. However, the calcium level was not normalized and the treatment was repeated with a further reduction in the calcium level. If immobilization is a major contributory factor to hypercalcaemia, disodium clodronate seems to be a safe and effective treatment.


Hematological alterations in kittens induced by 6 and 12% dietary propylene glycol.

Soft-moist cat foods containing 6-13% propylene glycol (PG) induce Heinz body formation and decreased red blood cell (RBC) lifespan in adult cats in a dose dependent manner. Since kittens eat relatively more food/kg of body weight and must expand their blood volume in addition to replacing senescent RBC, the hematologic dyscrasia associated with consumption of PG-containing diets may be exaggerated. To test this hypothesis 21 kittens were divided into 3 groups of 7 each and fed diets containing, 0,6 or 12% PG for 13 w. A dose-related increase in Heinz bodies occurred in the 6 and 12% PG groups within 2 w and persisted throughout the study. Although only slight changes occurred in hematocrit, hemoglobin and red blood cell (RBC) count, punctate reticulocytes increased significantly in the 6 and 12% PG groups indicating accelerated erythropoiesis. Mean RBC survival was decreased in the 6 and 12% groups by 44% and 63% respectively when compared to the control group. The increase in reticulocyte count and reduction in RBC lifespan was greater than observed in adult cats. The greater effect in kittens may be due to greater PG intake and not to an inate susceptibility of kitten RBC to PG.


[Eosinophilic gastroenteritis with serosa involvement. A rare differential diagnosis of ascites].

A 21 year old caucasian male suffered for 14 days from cramping abdominal pain, associated with nausea and vomiting. 6 weeks later he was admitted to our hospital because of rapidly increasing ascites. Further examinations led to the following decisive findings: Marked eosinophilia in the white cell count; marked eosinophilia in protein rich ascitic fluid; infiltration of serosal layer with eosinophils; no evidence for parasites in blood, faeces and ascites in multiple probes; no evidence for malignant or rheumatoid disease. Histology and cytology of probes obtained at laparoscopy led to the diagnosis of eosinophilic gastroenteritis with ascites. After low dose prednisolone therapy we observed a complete relief of symptoms and ascites disappeared.


[Significance of the ulcer vessel in acute ulcer hemorrhage--value of local endoscopic therapy in combination with endoscopic Doppler ultrasound].

The acute ulcer hemorrhage is one of the most frequent diagnoses in Gastroenterology. In addition to the active hemorrhage the visible ulcer vessel, even if not bleeding at present, is one of the most important prognostic criteria. Numerous controlled studies have shown that with this sign recurrent hemorrhages will occur in up to 81%, resulting in emergency surgery in up to 56% with an associated mortality of up to 21%. By a meta-analysis we could show that prophylactic endoscopic therapy can significantly reduce both the rate of recurrent hemorrhage as well as emergency surgery. If the endoscopic doppler is used as well, as diagnostic as well as follow-up examination, the effectiveness of endoscopic treatment is greatly improved. The numbers we present show that active local endoscopic therapy should be undertaken in a visible ulcer vessel.


Disability in Western Highlands Province.

During late 1987 and early 1988 the Mount Hagen Handicapped Children's Centre (as it was then known) set out to determine if substantial numbers of persons with disabling conditions lived within 15km of Mount Hagen town. The investigation located 1408 persons, deemed by themselves, family members or neighbours to have a disability.


Necrotizing crepitant cellulitis of the abdominal wall following a caesarean section and subsequent hysterectomy.

A case report of necrotizing crepitant cellulitis of abdominal wall following caesarean section is presented. Because of intense haemorrhage it was namely necessary to perform additional hysterectomy and bilateral hypogastric artery ligation. Serious wound infection and sepsis were successfully treated by administration of antibiotics and repeated deep incisions.


[Study of the epidemic significance of noncultivated forms of Vibrio cholerae by the polymerase chain reaction].

A specific method of the isolation of the cholera toxin gene by the directional amplification of DNA in the polymerase chain reaction (PCR) has been developed. The product of this reaction has a molecular weight of 440 sequence pairs and is a DNA fragment located on the A-subunit of V. cholerae gene vct. The sensitivity of the method permits the detection of one bacterial cell in the reaction mixture. The method is effective when V. cholerae purified DNA, cell lysates and the DNA of total microflora isolated from the water of natural springs are used. The study of water samples from natural water bodies by the method of PRC has revealed cholera toxin genes of V. cholerae noncultivated forms ni 5 out of 7 water samples taken from natural water bodies at the regions of Azerbaijan endemic for cholera and made it possible to evaluate the number of V. cholerae. The prospects of using PCR for the control of the epidemiological situation in regions endemic for cholera are discussed.


[Self-maintenance of foci of bovine leptospirosis].

The relationship between the rate of cattle infection with leptospirosis and the total number of livestock at cattle-breeding farms has been established. The annual dynamics of this infection has been found to give two morbidity rises among the animals, occurring not due to their contacts with the natural foci of leptospirosis, but as a consequence of the animal vertical and horizontal "circulation". The mechanisms of self-maintenance of the foci of leptospirosis among cattle are discussed.


[Laparoscopic surgery--the revolution in gallstone treatment].

The treatment of gallbladder disease is revolutionized by laparoscopic cholecystectomy (LCHE). Less pain postoperatively, earlier mobilization and a fascinating cosmetic result as well as a definitive cure of the disease have led to a fast acceptance by patients and doctors. From March 1990 to March 1991 we have performed 250 LCHE. Only 5 times we had to switch to the conventional procedure. 5 complications (1 lesion of the common bile duct, 2 biliary effusion, 1 abscess formation, 1 bleeding) were treated by laparotomy without further morbidity or lethality. Our rate of gallbladders operated by laparoscopy has increased from 35% in 1990 to 75% in 1991.


[Change in the income status of the disabled after introduction of long-term care insurance].

Up to the present time, long-term-care needs in the Federal Republic of Germany have only been covered to a limited extent through health insurance. The needs of the majority of those requiring long-term care must be covered from their pension funds or acquired wealth. This often does not suffice, which results in those needing long-term care becoming recipients of social assistance. The introduction of a long-term-care insurance should bring an end to this situation, which is considered unacceptable. At present, two competing schemes for covering the social risk of long-term care are being discussed: a social security insurance and a private insurance. When comparing the planned benefits under consideration, the social security insurance is more favorable in regards to nursing-home treatment, as well as with at-home care and benefits in kind. The private insurance is more favorable when considering nursing-home treatment and monetary benefits. If the private insurance is adopted, over 31% of those formerly relying on nursing-home care would no longer need social assistance. In the case of social security insurance, almost 46% would no longer require social assistance. Most of the remaining individuals requiring social assistance would be women.


[Infrequent cause of bilateral obstructive uropathy].

Muscular haematoma of the straight muscles of the abdomen are very rare to observe and, although there is a possibility of the haematoma extending to the retroperitoneum, they very rarely cause oligoanuria by compression of the urinary tract. Presentation of one case of spontaneous haematoma of the straight muscles of the abdomen with urologic damage by ureteral compression inducing oligoanuria and bilateral ureterohydronephrosis.


Mechanism of the modulation of murine peritoneal cell function and mast cell degranulation by low doses of malathion.

Malathion is a widely used organophosphate pesticide that modulates immune function at noncholinergic doses. Previous studies showed that this alteration in immune function was the result of enhanced macrophage function. In the present study, the effects of low doses of purified malathion (as low as 0.25 mg/kg malathion) administered orally to mice enhanced the respiratory burst of peritoneal cells. Microscopic examination of the peritoneal cells showed that mast cells were degranulated within 4 hr after malathion administration. The amount of beta-hexosaminidase, an enzyme released upon immunologic degranulation of mast cells, in the peritoneal lavage fluid of malathion-treated mice was also significantly elevated with 4 hours after malathion administration. Treatment of RBL-1, a rat basophilic cell line, cells with malathion, parathion or paroxon in vitro also led to the release of beta-hexosaminidase with paraoxon being the most potent. Further examination of the peritoneal cells of malathion-treated mice showed that the percentage of phagocytic peritoneal cells ingesting mast cell granules and the number of granules ingested per cell were elevated. These data suggest that malathion may enhance the respiratory burst of peritoneal cells through degranulation of peritoneal mast cells and the subsequent exposure to peritoneal cells to mast cell mediators.


Perceptions of parents of handicapped children concerning nurses and the health care system as it affects them.

Because of the change in mandate for Home Care Programs across Alberta, new cases of children with handicaps are now being assessed by nurses. Social workers, through the Handicapped Children's Services program, have traditionally been the ones to assess these children. This is a very new area for nurses and there is much to learn. Even less is known about the parents' perspective in working with families in community. As both a nurse working in the community and a parent of a child with special needs I see many of the issues from two sides. This study seeks to find out more about parents' feelings and views regarding nursing and the health care system. This knowledge is helpful to nurses working with these families as they strive to understand, communicate and build a helping relationship.


Effects of the immunomodulator diacetyl-splenopentin on antigen-induced arthritis in rabbits.

Long-term treatment with the immunomodulator diacetyl-splenopentin reduces the severity of chronic joint inflammation and cartilage destruction in rabbits with antigen-induced arthritis. The level of specific antibodies as well as specific and non-specific cell-mediated immune reactivities including the proliferative response of spleen lymphocytes to cartilage proteoglycans in treated animals are lower than in untreated arthritic rabbits. Moreover, suppressor cell activity, which normally decreases during the early phase of inflammation, is enhanced and hyperreactive helper cell potential is reduced. These findings suggest that treatment with diacetyl-splenopentin normalizes the immune regulation, which is disturbed in the early phase of inflammation. This might result in a depression of the hyperreactive immune system including the autoimmunity developed against cartilage. Lowered immune reactivity in the joint in turn reduces the severity of chronic joint inflammation.


Short- and long-term efficacy and safety of flecainide acetate for supraventricular arrhythmias.

This report summarizes efficacy and safety data on the use of flecainide acetate for supraventricular arrhythmias. For this purpose, 60 original articles were identified by a literature search representing data from 1,835 treatment courses. In 18 trials, flecainide was administered intravenously; in 19, orally; and in 23, both forms of therapy were applied. There were 5 placebo-controlled and 12 comparative studies, whereas data from uncontrolled studies were represented in 43 articles. Short-term flecainide administration terminated atrial fibrillation in 65% of attempts and terminated atrial flutter in 28%. The drug was effective during long-term therapy for atrial fibrillation in 49% of patients, with similar efficacy rates in 11 comparative trials and in 16 uncontrolled studies. In randomized, placebo-controlled studies in patients with paroxysmal atrial fibrillation, flecainide was shown to reduce significantly the number of attacks, to prolong the time between attacks, and to improve quality of life. In patients with atrioventricular (AV) reciprocating tachycardias, acute drug administration was successful in 72%; 83% of patients with AV nodal reentrant tachycardias and 74% exhibiting arrhythmias associated with the Wolff-Parkinson-White syndrome responded acutely. During long-term therapy, efficacy rates were 70%, 78%, and 69%, respectively. Ectopic atrial tachycardia responded in 86% and 95% of patients treated with flecainide acutely or chronically. Data concerning drug-related side effects were available for 1,794 of 1,835 treatment courses (98%). Overall, 352 of 1,794 patients (20%) reported at least one non-cardiac or cardiac adverse experience.(ABSTRACT TRUNCATED AT 250 WORDS)


A new classification of left ventricular geometry in patients with cardiac disease based on M-mode echocardiography.

M-mode echocardiograms of 202 cardiac patients were studied with respect to the pattern of left ventricular (LV) geometry. Patients with normal LV mass and volume were separated from those who had LV hypertrophy or enlargement on the basis of LV mass and volume indexed to body surface area. The relative wall thickness that is currently used to classify LV hypertrophy/enlargement was found to be inadequate for differentiating between concentric and eccentric types of LV hypertrophy. A new M-mode echocardiographic classification is therefore proposed that accurately separates the different types of LV enlargement; it also allows identification of patients who have chronically dilated left ventricles at the expense of thin walls and thus have normal LV mass.


Tensile strength of orthodontic brackets bonded directly to fluorotic and nonfluorotic teeth: an in vitro comparative study.

Information related to bonding of orthodontic brackets to fluorotic teeth is scanty. The purpose of this study was to compare, in vitro, the tensile bond strength and the bond failure site of brackets bonded directly to fluorotic and nonfluorotic teeth. The etching patterns were also evaluated. The study involved 26 teeth classified as score 3 and 4, and 26 as score 0 with the Thylstrup and Fejerskov's (TF) fluorosis index. In addition to the clinical classification, difference in the concentration of fluoride in the teeth was verified by acid etching. Brackets were bonded with a composite resin after etching the enamel surface with 40% phosphoric acid for 60 seconds. Tensile bond strength was determined with an Instron testing machine. The bond failure site was assessed by the percentage of residue cement on the tooth surface after debonding and the etching pattern by SEM. The mean concentration of fluoride was 2888.5 ppm (SD 1081.7) in the fluorotic teeth and 1227.1 ppm (SD 526.3) in the nonfluorotic teeth. The mean bond strength was 7.8 N/mm2 (SD 1.47) for the fluorotic teeth and 8.6 N/mm2 (SD 2.19) for the nonfluorotic teeth. The difference between the means for bond strength was not statistically significant (p greater than 0.05). Bond failure site was primarily at the bracket-adhesive interface. The mean percentage of adhesive on the enamel surface after debonding was 70% (SD 25.90) for the fluorotic teeth and 75% (SD 24.66) for nonfluorotic teeth. The difference in the means was not statistically significant (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Relations between sex hormone level and characters of hair and skin in healthy young men.

Total testosterone and dihydrotestosterone in blood serum as well as free testosterone in saliva were determined by radioimmunoassay in 110 healthy young men. The results were compared with the development of terminal hair on the trunk and limbs, with the disposition to balding and with the disposition to acne. No significant correlations were found between terminal hair development and absolute androgen levels; however, some significant values were observed in the case of the metabolic rate of dihydrotestosterone/testosterone and the proportion of free to total testosterone. The disposition to balding also correlates positively with the latter ratio. Yet the absolute serum androgen concentrations in men with a disposition to balding is lower than in men with no reduction of scalp hair. The widespread assumption that androgen levels are in general elevated in bald-trait men must therefore be rejected. In accordance with this finding, men with a disposition to balding are morphologically (with regard to anthropometric measures) no more masculine than those with good scalp hair growth. When body build and age are taken into consideration, the relations between terminal hair and androgen ratio are also problematical. No relationship could be found between acne and androgens.


Platelet reactivity to "in vitro" allergen challenge in asthmatic patients.

Platelet involvement in inflammation and allergic states is now well documented. In fact, it has been suggested that platelets can be triggered by either activated cells as monocytes and macrophages or by allergen itself. This latter possibility is still a matter of controversy. In this study we analysed platelet "in vitro" response to allergen, by optical aggregation technique, in 25 asthmatic patients, being 20 atopic and 5 non atopic patients. Platelet aggregation response to epinephrine, ADP, collagen and arachidonic acid was studied in all patients. In addition, allergen was added to platelet rich plasma and platelet reactivity was recorded both before and after stimulations with collagen. Platelet aggregation studies confirmed and abnormality of ADP induced platelet aggregation, that exhibited great variability among patients. In most cases this defect was the only one found in asthmatic patients and it should be further analysed. Results also showed a nonspecific response to allergen when dissolved in glycerol. This was due to glycerol rather than to allergen, since lyophilized allergen did not affect platelets, and glycerol added to platelet rich plasma induced the same type of curve. So, allergen by itself does not imply platelet aggregation. Experiments with IgE did not provoke either platelet agglutination or platelet aggregation. Furthermore, previous incubation with allergen immediately before collagen induced aggregation did not significantly change platelet response. This study allows the conclusion that platelet reactivity to allergen contact must be an expression of multicellular cooperation rather than a direct effect on platelet IgE receptors stimulation.


Expression of vacuolar H(+)-ATPase in mouse osteoclasts during in vitro differentiation.

Osteoclasts express high levels of a vacuolar H(+)-adenosinetriphosphatase (H(+)-ATPase) on the ruffled membrane which they employ to dissolve bone mineral by acidifying their site of attachment on bone. The factors that control amplification of H(+)-ATPase during osteoclast differentiation are poorly understood. We examined the expression of vacuolar H(+)-ATPase in a cell culture system in which mouse spleen cells can be induced to differentiate into osteoclasts by coculture with a mouse bone marrow stromal cell line. We found that the coculture system produced active osteoclasts, identified as multinucleated cells with staining for tartrate-resistant acid phosphatase activity that formed genuine resorption pits in bone. These cells developed high levels of H(+)-ATPase expression in culture, and omission of dexamethasone or 1 alpha,25-dihydroxyvitamin D3 from the coculture system each partially suppressed the expression of H(+)-ATPase. The results demonstrate that the spleen and PA6 cell coculture system may be useful for investigating the factors that control the induction of H(+)-ATPase amplification that occurs during osteoclast differentiation.


Neutrophil chemiluminescence following exposure to formaldehyde in healthy subjects and in patients with contact dermatitis.

13 formaldehyde-sensitive contact dermatitis patients and 5 healthy subjects were exposed to formaldehyde (FM) at a concentration 0.5 mg/m3, in an exposure chamber for 2 hours. There was no significant decrease of the ventilatory parameters either in healthy subjects or in contact dermatitis patients following the exposure Bronchial hyperreactivity to histamine (PC20) increased in one healthy and two patients with contact dermatitis. Neutrophils were isolated from whole venous blood before the test and 30 minutes and 24 hours after the exposure. All subjects with allergic contact dermatitis had chemiluminescence higher before the FM provocation in a comparison with the healthy ones. It increased significantly 30 minutes post the exposure and was much higher 24 hours after the exposure in the comparison with the neutrophil chemiluminescence before the test.


Sliding velocity of isolated rabbit cardiac myosin correlates with isozyme distribution.

To investigate the relationship between the mechanical and biochemical properties of cardiac myosin, the sliding velocity of isolated cardiac myosin obtained from both euthyroid and hyperthyroid rabbits on actin cables was measured with an in vitro motility assay system. Ten rabbits (T) were treated with L-thyroxine to induce hyperthyroidism, and eight nontreated animals (N) were used as controls. Myosin was purified from the left ventricles of anesthetized animals. Myosin isozyme content was analyzed by the pyrophosphate gel electrophoresis method, and myosin adenosinetriphosphatase (ATPase) activity was determined on the same sample. Long well-organized actin cables of green algae, Nitellopsis, were used in the in vitro motility assay. Small latex beads were coated with purified cardiac myosin and introduced onto the Nitellopsis actin cables. Active unidirectional movement of the beads on the actin cables was observed under a photomicroscope, and the velocity was measured. The velocity was dependent on ATP concentrations, and the optimal pH for bead movement was approximately 7.0-7.5. The mean velocity was higher in T than in N (0.66 +/- 0.12 vs. 0.32 +/- 0.09 micron/s, P less than 0.01). Both Ca(2+)-activated ATPase activity and the percentage of alpha-myosin heavy chain were also higher in T than in N (0.691 +/- 0.072 vs. 0.335 +/- 0.072 microM Pi.mg-1.min-1, P less than 0.01, and 79 +/- 12 vs. 26 +/- 7%, P less than 0.01, respectively). The velocity of myosin closely correlated with both Ca(+2)-activated myosin ATPase activity (r = 0.87, P less than 0.01) and the percentage of alpha-myosin heavy chain (r = 0.87, P less than 0.01).


Vasopressin modulates K(+)-channel activities of cultured smooth muscle cells from porcine coronary artery.

The ATP-sensitive K+ channel (KATP channel) and the Ca(2+)-activated K+ channel (KCa channel) were active in cell-attached and excised inside-out patch configurations in cultured smooth muscle cells of the porcine coronary artery. Vasopressin activated the KCa channel (240 pS) when it was applied in the bath in the cell-attached patch mode presumably because of an increase in intracellular Ca2+, but it had no direct effect on the KCa channel. However, vasopressin directly blocked the KATP channel from outside the cell membranes in a concentration-dependent manner in both outside-out and cell-attached patch configurations; the K(+)-channel opener, nicorandil, reversed this effect. The KATP channel (30 pS) was highly active in the intact cell-attached patch configuration when the pipette contained a physiological concentration of Ca2+, suggesting that this channel may control the resting membrane potential. (The block might produce depolarization of the cells and might result in the contraction of smooth muscle cells.) These observations suggest that the KATP channel may play a role, at least in part, in controlling the contraction of smooth muscle cells of the coronary artery and that the control of vascular tone by vasopressin may be related to its ability to block the KATP channel.


Effects of atrial natriuretic peptides on metabolism of arginine vasopressin by isolated perfused rat kidney.

Atrial natriuretic peptide (ANP) antagonizes the release and action of arginine vasopressin (AVP) both in vivo and in vitro. We have reported that ANP increases the urinary and metabolic clearances of AVP in normal subjects (A. M. Moses et al. J. Clin. Endocrinol. Metab. 70: 222-229, 1990). To clarify this effect, we perfused isolated rat kidneys in vitro and measured the clearances of AVP for 30 min after the addition of rat ANP [rANP-(1-28), 10(-7) M]. In the perfused kidney, rANP increased the urinary clearance of AVP (UCAVP) from 321 +/- 19 to 417 +/- 20 microliters/min (P less than 0.01) and increased the glomerular filtration rate (GFR) from 558 +/- 28 to 696 +/- 28 microliters/min (P less than 0.01). Fractional excretion of AVP was unchanged. Rates of AVP reabsorption were directly related to filtered AVP, and this relationship was not altered by ANP. ANP did not affect the total organ clearance or the renal metabolic clearance of AVP. The increase in GFR was associated with increases in renal vascular resistance (P less than 0.05), filtration fraction (P less than 0.01), and sodium excretion (P less than 0.001). UCAVP also increased when GFR was raised without ANP by perfusing at higher pressures. The rat ANP clearance receptor agonist [cANP- (4-23), 10(-7) M] did not change GFR or UCAVP. ANP increases UCAVP in the isolated perfused rat kidney. This appears to be a hemodynamic effect of ANP, acting through its biological receptor and not the clearance receptor.(ABSTRACT TRUNCATED AT 250 WORDS)


Rat brain natriuretic peptide is localized in atrial granules and released into the circulation.

Rat brain natriuretic peptide (BNP) was detected by radioimmunoassay in heart atria and ventricles and in plasma. We have investigated its localization in atria and the possibility of cosecretion of atrial natriuretic factor (ANF) and BNP into the circulation. BNP was detected by chromatographic analysis and immunoblotting in the isolated atrial granules together with ANF: It consisted of two immunoreactive proteins of 14,000 and 2,500 apparent molecular weight. By immunohistochemical methods, BNP was particularly found in the perinuclear region of atrial cardiocytes. Double-labeling immunocytochemical methods colocalized BNP and ANF in the same atrial secretory granules. Basal plasma BNP levels ranged from 2.6 to 4.4 fmol/ml. After stimuli by morphine injection or an aortocaval shunt, BNP levels increased by 4- and 7-fold, respectively, whereas ANF levels rose by 50- and 6-fold, respectively. Depending on the stimulus, BNP release into the circulation is not necessarily proportional to ANF, indicating that BNP may originate not only from the atrial granules but also from other tissues such as the ventricles. These results suggest that BNP may participate with ANF in blood pressure control and salt and water homeostasis.


Dexamethasone stimulates release of an ANP-like substance from rainbow trout cardiocytes.

A substance that cross-reacts with antiserum to human atrial natriuretic peptide (ANP) is found in fish hearts. This ANP-like material increases sodium output from the gill and kidney while inhibiting sodium uptake in the gut. Mammalian ANP secretion is stimulated by glucocorticoids, and cortisol injection increases sodium output in salt-loaded fish. Therefore, we wanted to determine if the release of ANP in fish is sensitive to dexamethasone. Ventricle cardiocytes from the rainbow trout Oncorhynchus mykiss were treated with various doses of dexamethasone for 18 or 72 h. Single ventricle cells were then assayed for ANP release using a reverse hemolytic plaque assay and antiserum to human alpha-ANP. Incubation with 100 microM dexamethasone almost doubled the population of ventricle cells committed to ANP release (basal, 15.0 +/- 0.3% vs. Dexamethasone, 28.3 +/- 1.4%; values are percent plaque formation +/- SE). Stimulation of ANP secretion was dependent on dose and time of exposure to dexamethasone. These results suggest that ANP secretion in fish is regulated by glucocorticoids.