The role of cytokines in the pathogenesis of hepatic granulomatous disease in Schistosoma mansoni infected mice.

Cytokines are important in the cell-mediated response to Schistosoma mansoni eggs. We have found that Th2 cytokine responses (e.g. IL-4 and IL-5) are augmented after egg laying begins while Th1 responses (IL-2 and IFN-gamma) are down regulated in S. mansoni infected mice. Treatment of mice with anti-IL-5 monoclonal antibodies (Mab) suppressed the eosinophil response almost completely but did not affect granuloma size and slightly increased hepatic fibrosis. Anti-IL-4 treatment abolished IgE responses in infected mice and decreased hepatic fibrosis slightly. Anti-IFN-gamma treatment had no effect on hepatic pathology. Anti-IL-2 treatment decreased granuloma size significantly and decreased hepatic fibrosis markedly. Anti-IL-2 treatment dramatically decreased IL-5 secretion by splenic cells in vitro and decreased peripheral blood and tissue eosinophilia. In contrast IL-4 secretion was unaffected and serum IgE was normal or increased. IL-2 and IFN-gamma secretion by splenic cells of treated mice were slightly but not significantly increased suggesting that anti-IL-2 treatment is affecting Th2 rather than Th1 responses.


The susceptibility of adult schistosomes to immune attrition.

Mouse infection models are described that demonstrate reduction of egg production in Schistosoma haematobium infections and both worm loss and reduced fecundity in S. bovis infections. Neither phenomenon could be shown in S. mansoni infected mice. The immunological basis for these anti-adult responses was inferred by comparison with infections in T-cell deprived mice and by serum transfer of the ability to reduce a S. bovis worm burden into immunocompromised hosts. Vaccination with irradiation attenuated parasites was also shown to have consequences for the adults of a challenge infection of S. haematobium and S. bovis specifically. Prior vaccination resulted in an abrogation of the anti-fecundity and adult worm elimination that occurred in non-vaccinated similarly infected mice. These models are being used to define the targets and mechanisms involved in anti-adult attrition. A serological assay, quantitation of a circulating antigen (CAA) has been assessed for its ability to measure worm burdens of different species of schistosome in mice. This assay will be used to question whether anti-adult immunity contributes to the pattern of infection with S. mansoni and S. haematobium in man.


Recent advances in immunity to human schistosomiasis.

For many years the epidemiological significance of immunity in human schistosomiasis has been the subject of inconclusive debate. Recently, the results of studies from Brazil and Kenya, on Schistosoma mansoni and from Zimbabwe and The Gambia on S. haematobium have confirmed the importance of protective immunity. In communities in endemic areas the development of immunity to infection only occurs after many years of exposure. In part this is due to the slow development of antibodies which are protective but also to the earlier development of antibody isotypes which lack protective capacity and which are capable of interfering with the functioning of protective antibodies. Protective antibodies appear to be of the IgE class but some IgG subclasses may also be important. Initially, blocking antibodies were thought to be predominantly IgM and IgG2 but IgG4 also seems to possess blocking activity. The early production of blocking antibodies and late production of protective antibodies may be indicative of cytokine induced immunoglobulin class switching caused by the sequential involvement of different lymphokines.


Human IgE responses to Schistosoma mansoni and resistance to reinfection.

Schistosoma mansoni infected Kenyan patients were treated and the intensities of their reinfections were followed over the next two years. In addition, their pre- and six month post-treatment serum levels of IgG1-4, IgM, and IgE, specific for schistosomula, egg and adult worm, were measured in ELISA. No reinfection took place before six months post-treatment. Reinfection intensities varied with age; the younger children becoming reinfected at significantly higher intensities than older individuals. When antibody and reinfection levels were compared, only the six month post-treatment IgE response against adult worm correlated negatively with intensities of reinfection and, therefore, was predictive of resistance or immunity to reinfection. IgE and IgG specific Western Blots were carried out. The adult worm antigens recognized by IgE were restricted compared with the IgG responses of the same patients, although no individual antigen was uniquely recognized by the IgE isotype. A dominant 22 kDa antigen was recognized by most but not all high IgE responders. Patients with IgE responses against this antigen suffered significantly lower subsequent levels of reinfection, compared with non-responders. A monospecific rabbit antiserum against the 22 kDa adult worm antigen showed that this antigen is specifically located in the tegument of the adult worm and of 'lung' and 'liver' stage schistosomula, but is absent from the early 'skin' schistosomula. It is possible that this antigen is a target for human IgE mediated immune effector mechanisms active against the post skin stage schistosomula and that this is boosted by the death of adult worms.


The mouse ligated intestinal loop assay for the studies on enteroinvasive Escherichia coli.

Enteroinvasive Escherichia coli exhibited a positive reaction in the mouse intestinal loop assay except for noninvasive mutant strains. These mean values of fluid weight per gut length of mouse loops inoculated with enteroinvasive E. coli were significantly higher than that given by brain heart infusion broth. Oedema and swelling in all positive loops, increased bacterial cell numbers within intestinal loops were observed.


Phospholipid content of untreated and insulin treated cells of Neurospora crassa (wall-less strain).

Phosphatidylcholine (51.2%) and phosphatidyl-ethanolamine (38.3%) are the most abundant phospholipids in the wall-less strain of Neurospora crassa. Insulin treatment exerted no change on the amount of phosphoinositides, although some previous results proved the existence of specific insulin receptors and specific effect of insulin on glucose metabolism in these cells. Long (20 h) treatment with insulin also failed to cause biologically significant changes.


The course of LCMV infection in euthymic and athymic mice pretreated with immunomodulatory agents.

Balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with TP-4 (a synthetic tetrapeptide, thymopoietin sequence analog) or with Mannozym (1% zymosan suspension), and were infected intracerebrally with LCM virus. Both of the agents contributed to the development of fatal choriomeningitis, consequently stimulated the cellular immune response in euthymic mice, but the athymic mice either treated or not, survived the infection, consequently the agents had no effect on the course of LCM virus infection. Both agents exerted a thymus-dependent cellular immune response stimulating effect. That is, an immunostimulatory effect can be realized only in the presence of the thymus or the T-dependent lymphoid system.


Anthraquinone pigments production by brown mutant Trichoderma viride M-108 under various nutrition conditions.

In this work the influence of 12 carbon and 9 nitrogen sources on pigment production of brown mutant Trichoderma viride M-108 was tested. There were two concentrations of nutrient sources used and the tests were carried out in three light regimes. The pigmentation was good only on media containing sodium nitrate, sodium nitrite, sucrose, starch and glycerol and there was no pigment production on media with adenine, ammonium chloride and ammonium sulphate. In mixtures of pigments, individual compounds were determined by using thin-layer chromatography and UV spectra of colour fractions.


Reversion of UV light morphological and colour mutants of Trichoderma viride.

By using UV light 13 years ago from Trichoderma viride 8-7 Pers. ex S. F. Gray 82 colour and morphological mutants were prepared. The reversion of these mutants was high and in 1985 only 26 stable mutants (i.e. 32%) could be used for genetic studies. In 1991, from these 26 mutants we had only 6 stable types (i.e. 7.3% from the original state). These mutants were permanently transferred on fresh CzDA medium every 3-4 months and checked for morphology, growth, conidiation, heterokaryons and diploids production. The group of mentioned mutants was enlarged with mutants which were after 3-4 transfers on fresh medium, preserved dried to the present time. The largest differences were observed in microscopic appearance of colonies. Differences between growth rates, intensity of conidiation were comparable with those made 13 years ago.


Ochratoxigenicity of Aspergillus ochraceus group and Penicillium verrucosum var. cyclopium strains on various media.

Production of ochratoxin A (OA) by strains of Aspergillus ochraceus group (A. ochraceus--21, A. sclerotiorum--1, A. sulphureus--1) and Penicillium verrucosum var. cyclopium strains--11, on various media was investigated. Thirteen percent of A. ochraceus strains and 18% of P. verrucosum var. cyclopium formed OA growing on sterile crushed wheat for 14 days at 25 to 27 degrees C (preliminary experiments). Toxin concentrations were 5.0 to 7.0 micrograms/kg. Five strains OA-positive on crushed wheat and four OA-negative strains were cultivated on various liquid nutritional media (YES, RM, OAT, CG and AFP). All the strains tested, including OA-negative ones, produced OA on certain liquid media. Concentrations of OA were low again (trace to 16.0 micrograms/l). The largest number of mould strains examined produced OA on YES (55.5%) and RM media (44.0%), but the highest concentration (16.0 micrograms/l) was formed on YES and CG media.


Antibodies against invasion plasmid coded antigens of shigellae in human colostrum and milk.

Colostral and milk samples of Swedish, Vietnamese and Costa Rican mothers living under various socioeconomic conditions were tested for the presence of shigella invasion plasmid coded antigen (Ipa) specific antibodies. IgA antibodies of this specificity were found in significantly higher titres in samples of Vietnamese (600 +/- 338) than in samples of Swedish or high income Costa Rican mothers (190 +/- 224 and 290 +/- 241, respectively; p < 0.05). Specific IgA titres in the low income group of Costa Rican mothers (470 +/- 338) did not differ significantly from the values obtained in Vietnam. While no Ipa specific IgM could be detected in any of the samples tested, specific IgG was found in 90% of the Vietnamese colostrum. These data indicate that antibodies which could be responsible for the dysentery-preventing effect of breast feeding are indeed present in human colostrum and milk in areas where shigellosis occurs with relatively high incidence.


Effect of inhibitors of HeLa cell structures and functions on Escherichia coli HB101 (PRI203) entry process.

We investigated the effect of some eucaryotic cytoplasmic structure and function inhibitors on the entry into HeLa cells of the Escherichia coli HB101 K12 strain, harbouring the recombinant plasmid pRI203, in which is cloned a 3.2 Kb chromosomal fragment of Yersinia pseudotuberculosis. Substances impairing microfilament structures and functions (cytochalasin B and trifluoroperazine) significantly reduced invasion ability whereas microtubule organization inhibitors (colchicine and vinblastine) were ineffective. Data obtained with a lipophilic weak base (methylamine), which raises the pH of intracellular vesicles, demonstrated that, in entry pathway of E. coli HB101 (pRI203), endosome acidification is not required. Host cell energy has been shown to contribute to bacterial internalization since the presence of oxidative phosphorylation and glycolysis inhibitors (sodium azide, 2-dinitrophenol and 2-deoxy-D-glucose) during the invasion process, affected bacterial entry.


Chloroquine inhibits the insulin binding and the imprinting of nuclear envelope in Tetrahymena.

Chloroquine possessing lysosomotrop effects inhibits the development of insulin imprinting both on the plasma membrane and the nuclear envelope. Simultaneously chloroquine can inhibit the insulin binding in the nucleus itself but not in the plasma membrane. There is a dose dependent increase of binding of labelled insulin to the nuclear envelope. The control related binding of nuclei pretreated with insulin or chloroquine is similar and have a direct ratio, independently of the applied concentrations.


Evaluation of indirect enzyme linked immunosorbent assay for the detection of coxsackieviruses in clinical samples and its comparison with dot-immunobinding assay.

Indirect enzyme linked immunosorbent assay (ELISA) was applied for the direct detection of coxsackieviruses in clinical samples viz. rectal swabs (RS) and throat swabs (TS) collected from patients admitted to various nursing homes and local hospitals. Results indicate the presence of different CVA types in 65 (62.5%) out of 104 RS, and 18 (52.9%) out of 34 TS samples. Dot-immunobinding assay was also standardized for the identification of CVA types employing 52 RS samples and the results compared with indirect ELISA. Dot-immunobinding detected more CVA types in a relatively larger number of specimens than indirect ELISA.


Latex agglutination and adenoviruses. I. Detection of polyclonal antibodies by latex agglutination test.

A latex agglutination (LA) test was developed for the detection and measurement of polyclonal anti-adenovirus antibodies. Latex particles, coated with purified hexon, penton or fibre antigens displayed specific agglutination with 21 rabbit immune sera directed against the different antigens and the complete virus of 10 human and 2 animal adenovirus types. The sensitivity of LA was compared to that of passive haemagglutination, complement fixation (CF) and immunodiffusion reactions. In experiments with immune sera as well as with human serum samples the sensitivity of LA test proved to be in the same range as that of CF test. Because of its easy and rapid performance (slide agglutination within 4 min) LA method may substitute for CF reaction in serological adenovirus diagnosis.


Diazald, a newly recognized antimicrobial agent and its spectrophotometric determination.

Diazald, a chemical intermediate for the synthesis of biologically active compounds, was found to be a potent in vitro antimicrobial agent against yeasts, yeast-like and filamentous fungi as well as Gram-positive and Gram-negative bacterial strains. Its activity is not inhibited by either para-aminobenzoic acid (PABA) or the nitroso group-specific 2-aminothiazole-methoxyimino acetic acid (ATMAA). This suggests that the molecule as such is responsible for the antimicrobial activity. For its quick measurement a sensitive spectrophotometric method has been developed.


Adherence of ruminal Streptococcus bovis and Lactobacillus strains to primary and secondary cultures of rumen epithelium.

Six strains of rumen Lactobacillus and four Streptococcus bovis strains isolated from rumen wall and fluid samples were examined for the adherence to cells of primary and secondary cultures of ruminal epithelium (REC) prepared from sheep and calf. S. bovis adhered to the keratinized REC. Ruminal lactobacilli did not adhere. The presence of rumen lactobacilli in mixture had no influence on the adherence of S. bovis strains. No difference was observed in the adherence of tested bacteria to epithelial cells of primary or secondary cultures, but adhesion was only detected on keratinized cells.


Strategies for implementation and quality assurance for mammographic screening.

Compliance with screening mammography guidelines is affected by complex factors, including cost, accessibility, education, and attitudes of referring physicians. High-volume mammography facilities have lower fees and higher quality. Quality assurance is the focus of the voluntary American College of Radiology Mammography Accreditation Program, and over half of all mammography units are accredited. Nonetheless, pressure for mandatory quality standards is increasing. Mobile mammography reduces costs and increases access, but it presents challenges in financing and quality assurance. These screening issues, especially quality assurance, are not taught adequately in radiology residency training programs. Yet public awareness of the benefits of early detection has resulted in more lawsuits for failure to diagnose and delay in diagnosis. Preventive measures reduce medicolegal risks. On a personal level, the psychologic trauma of screening mammography is greater than was previously suspected. However, associated anxiety and stress do not seem to affect compliance with screening guidelines adversely.


Thoracic intervention.

The literature of the past year regarding interventional procedures in the thorax covers aspects of transthoracic needle biopsy, drainage of pleural fluid collections, percutaneous management of lung abscess, and thoracic vascular interventions. Topics in transthoracic needle biopsy include a large retrospective series on fluoroscopically guided biopsy of thoracic masses; several reports reviewing experience with diagnosis of anterior mediastinal masses, including four studies describing the use of real-time ultrasound guidance for this procedure; the description of a new automated cutting needle for consistent tissue sampling; and two studies addressing factors affecting pneumothorax and chest tube insertion rates following transthoracic needle biopsy. Reports on percutaneous management of pleural fluid collections are highlighted by a paper reporting the results of ultrasound-guided drainage and sclerosis of malignant pleural effusions. Ultrasound-guided percutaneous aspiration of lung abscess for isolation of causative bacteria is the basis of two recent papers, and successful CT-guided drainage of lung abscesses is described by a group of researchers that has written extensively on a variety of the interventional thoracic procedures that are currently performed. Finally, the failures and complications associated with bronchial and pulmonary arterial embolization procedures have been reviewed.


Kilovoltage peak and half value layer relationships of a dental X-ray machine.

This study compares the recorded kilovoltage peak (kVp) on the control panel versus actual kVp measured by the Photon Physics instrument and Non-invasive Evaluator of Radiation Output (NERO) System. The study also measures the effects of kVp and milliampere (mA) on Half Value Layer (HVL). Kilovoltage peak was measured using a photon physics instrument and the NERO system. Half value layer was measured using aluminum as the absorber. The kVp and HVL were measured from 50 to 100 kVp at 5 kVp intervals using both 10 mA and 15 mA. Results show a 2 to 6 kVp difference between recorded kVp on the control panel of the dental x-ray machine and measured kVp using the photon physics instrument. There was 10-15 kVp difference between the recorded kVp on the control panel and kVp measured with the NERO Quality Assurance System. The measured kVp on photon physics or NERO system was always greater than the recorded kVp on the control panel. The HVL increased as the kVp increased for both 10 mA and 15 mA settings. However, above 80 kVp, the HVL increase was not significant.


Cementum and bone: a histomorphometric study.

In the present study, a series of cementum and bone specimens were examined both qualitatively and quantitatively with a view to establishing histological criteria which may help in differentiating cementum from bone. This is for the first time that differences in cellularity and width of fibre bundles between the lamellar bone and the cementum has been reported.


Evaluation of decalcified allogenic bone matrix grafts in and around root apices. A histological study.

Decalcified Allogenic Bone grafts were implanted in and around eighteen root apices after apicoectomy. The procedure was carried out on eighteen rabbits, dividing them into three groups of six rabbits each. The animals were sacrificed after 48-72 hours, 8-10 days & 8-10 weeks period of interval. Result of the present investigation reveal that DABM grafts stimulate osteogenesis and cementogenesis after the initial phase of inflammation. Tissues simulating bone and cementum appear at the apical end, speculating that the grafts would certainly result in physiological sealing of root apices. The possibility of saving the life of non vital teeth with or without wide apical foramen will enhance in future.


Osteoradionecrosis of mandible in patients treated with definitive radiotherapy for carcinomas of oral cavity and oropharynx. A retrospective study.

A retrospective analysis of 1140 cases of cancer of oral cavity and oropharynx treated with definitive radiotherapy was carried out with regard to the incidence and precipitating factors of mandibular osteoradionecrosis. 14 cases developed osteoradionecrosis out of which 10 had spontaneous mandibular necrosis and 4 had dental extractions in the area where osteoradionecrosis developed. Amongst the 10 cases of spontaneous osteoradionecrosis, 8 patients received doses of 6500 cGy in 6 1/2 weeks or 7000 cGy in 7 weeks by megavoltage cobalt 60 teletherapy and the remaining two patients received the doses of 6000 cGy in 6 weeks. The aforesaid 4 patients of osteoradionecrosis in the area of dental extractions had received doses of only 6000 cGy in 6 weeks.


Influence of opioids on LH secretion in gilts during the estrous cycle.

The effect of endogenous opioid peptides (EOP) on LH secretion is variable during different physiological states. A series of experiments concerning the role of EOP on LH secretion in cyclic gilts was performed. They were comprised of (1) an administration of an opioid antagonist or agonist in gilts during the estrous cycle and in ovariectomized (OVX) gilts in which the LH surge was induced with estradiol benzoate (EB) and (2) in vitro studies on GnRH release from the stalk median eminence (SME) of cyclic gilts and OVX estrogen and progesterone primed gilts in response to naloxone (NAL). Naloxone and met-enkephalin analogue (FK 33-824) administration as a single independent injections did not affect LH secretion during the early (Day 16) or late (Day 19 or 20) follicular phase. However, continuous infusion of FK 33-824 for 4 h decreased LH secretion during the infusion period on Day 19 of the estrous cycle. Morphine also exerts an inhibitory effect on the EB-induced LH surge during the positive feedback phase (60-64 h after EB administration) in OVX gilts. On the contrary, NAL infusion in OVX gilts during the negative feedback phase (30-34 h after EB administration) did not alter LH secretion. A single injection of FK 33-824 in luteal phase gilts decreased the number of LH pulses for a 3 h period. This allows to hypothesize that EOP participates in the regulation of pulsatile LH secretion in pigs during the luteal phase. In vitro studies indicate that influence of EOP on LH secretion also takes place at the SME level. GnRH efflux from the SME of gilts during the luteal and late follicular phases was augmented in the presence of NAL. Unexpectedly, the priming of OVX gilts with estrogens caused the highest increase in GnRH release from the SME in vitro in response to NAL. These results confirm the variety of functional links between the opioid system and LH secretion in gilts during different stages of the estrous cycle.


Caridex: dentin topography and bond strength evaluation.

CARIDEX, is a new approach to pediatric operative dentistry. An in vitro study with the aim of comparing the efficacy of the CRS system against the conventional caries removal system was carried out by studying the dentin topography following caries removal by the two systems restorative materials--Silver amalgam, Composite resin, Glass Ionomer, IRM nad Poly--F to the CARIDEX treated dentin using the Housfield Tensometer. The results were evaluated statistically and significant results were observed.


Regulation of bovine intra-luteal function by peptide hormones.

There is increasing evidence for the existence of substances in ovarian tissues and fluids which are able to act locally, either alone or by modulating the actions of the gonadotropins, thus modifying the functions of ovarian cells. There are now clear data for oxytocin (OT), insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) in luteal tissue, with regard to specific expression of mRNA, secretion of peptid and receptors. Biological effects of these growth factors and others on luteal tissue were determined during the estrous cycle using two different in vitro systems; a novel microdialysis system (MDS) of intact luteal tissue and culture of luteal cells. The concentrations of secreted progesterone and OT were used as parameters. MDS; OT was most stimulative during the early luteal phase (days 5-7) and decreased continuously from days 8-12 to days 15-18. During early and mid stages bFGF was the most potent stimulator and at the late stage IGF-1 and IGF-2 were most stimulatory. Transforming growth factor beta (TGF-beta) stimulated the release of OT most effective at the early luteal stage. Results from the cell culture system (where no cell to cell contact exists) showed a different pattern. IGF-1 and IGF-2 had a stimulatory effect during long and short term stimulation, bFGF only during short term and OT showed no effect. Receptors were found for all peptides examined of luteal cells. A model of an intraovarian cascade-like system for the amplification of luteal function is presented.


Role of the noradrenergic system in the secretory function of the corpus luteum.

The importance of sympathetic innervation changed significantly during sexual maturation and in the course of the oestrous cycle in females. Basal secretion of progesterone is partly dependent on constant beta-adrenergic stimulation since local infusion of propranolol (beta-blocker) into the ovary decreased progesterone secretion by 20-30% of pre-treatment value. Noradrenaline given into the abdominal aorta in the moderate doses affected very quickly and dramatically the secretory function of the corpus luteum during the luteal phase in cattle and also in other species. Thus short-lasting mobilization stress protects and even supports corpus luteum function. This effect is exerted through the stimulation of beta-adrenoceptors which then activates specific intracellular enzymes. Additionally noradrenaline acts upon vascular alpha-receptors and increase ovarian blood flow allowing utilization of serum-derived lipoprotein as a source of cholesterol for steroidogenesis. The highest amount of specific beta-receptors in luteal membranes was found in the newly-formed corpus luteum which does appear to require noradrenergic support especially at that stage of its development. The mechanism of noradrenaline influence upon luteal cells resulting concomitant progesterone and ovarian oxytocin secretion is, however, obscure. It is suggested that intracellular second messengers (cAMP, Ca2+) involved in noradrenaline action can simultaneously affect the secretion of both these hormones and this indicates some functional relationship between them. The presented results are focused mainly upon cattle due to the importance of this species among other domestic animals. Nevertheless for comparison data from other species are also quoted.


Arterial blood pressure and blood glucose levels in oral lichen planus patients in Calcutta (India).

The Arterial Blood pressure and Blood Glucose levels of 192 patients with Oral Lichen Planus was determined. A control sample of 5000 healthy individuals was also studied for comparison with the oral Lichen Planus cases. No significant difference was found between oral Lichen Planus patients and the general population with respect to Blood pressure and Blood Glucose values.


Experimental and practical approaches to the establishment and maintenance of pregnancy.

A series of three large field trials was carried out to assess the effect of buserelin on fertility in dairy cows. In the first, 10 micrograms buserelin was injected on the day of insemination. There were no significant effects on fertility parameters compared to untreated controls. In the second trial cows were injected on day 12 after insemination. Mean pregnancy rates to first insemination were 53.4 and 65.4% for control and treated cows respectively (P < 0.01). Mean pregnancy rates to repeat inseminations were 52.9 and 59.4% for control and treated cows (NS). Mean calving to conception intervals were 91.4 and 85.3 days (P < 0.01) and the incidence of barren cows was 10.2 and 5.3% (NS). Overall the economic benefit of buserelin injection on day 12 was calculated to be 27.43 pounds per cow treated excluding the cost of the treatment. In trial 3 cows were injected with buserelin either on day 8 or 10 after insemination. There were no significant effects on fertility parameters compared to untreated control cows. In a fourth trial ewes were injected with 4 micrograms buserelin on day 12 after service. There were indications that both pregnancy rate and lambing percentage could be increased by buserelin treatment. Daily blood samples were collected from 5 dairy cows during a control cycle and a cycle in which 10 microgram buserelin was injected on days 11 and 13. Cycle length was unaffected by treatment and the concentration and pattern of progesterone secretion did not differ between control and treated cycles. Plasma oestradiol concentrations were similar in the control and treated cycles before day 11. However from day 12 to 16, equivalent to the time of maternal recognition of pregnancy, the mean concentration of oestradiol was significantly reduced in the treated cycle. As oestradiol stimulates both the development of uterine oxytocin receptors and the secretion of PGF2 alpha we suggest that any improvement in pregnancy rate after buserelin is due to a weakened luteolytic mechanism, resulting from a lower plasma oestradiol concentration.


Electrogustometry in oral submucous fibrosis. A study in 50 cases.

Taste sensation were evaluated in 50 cases of Oral Submucous Fibrosis. Ankyloglossia was present in 28% and ulceration of tongue in 6% of cases. None of the cases had subjective impairment of taste sensation. Electrogustometry revealed impairment of taste in 46% of cases. Ankyloglossia was found to be related with the severity of Oral Submucous Fibrosis but impairment of taste was not related with the severity of the disease. The possible mechanism of the impairment of taste is discussed in brief.


Regulation of steroidogenesis in the bovine placenta.

As pregnancy progresses in the cow, the secretory activity of the corpus luteum is markedly diminished. This reduced secretion is due to a decline in the number of viable luteal cells as well as reduction in the secretory activity and responsiveness of the cells to trophic agents. The principal extra-ovarian source of progesterone (P4) by mid-gestation therefore appears to be the placenta. Uniquely this P4 biosynthesis is cyclic-nucleotide independent, but the Ca+2 dependent. It therefore appears that the Ca+2 second messenger and protein kinase C systems are responsible for regulation of sterol biosynthesis in the cow placenta. Dispersed bovine caruncle cells from the first trimester of pregnancy in comparison to caruncle cells of older than 90 days of gestation produce little P4 and are refractory to agents which enhance placental steroidogenesis. In order to explain this refractoriness of the first trimester cells, we determine (1) the expression of P450scc and its mRNA and (2) the expression of adrenodoxin. It was found that P4 synthesis by bovine maternal caruncle cells was low or undetectable in the first trimester but increased more than 10-fold in the second trimester of gestation. Addition of 25-OH-cholesterol to second trimester maternal cells increased P5 production but no effect was observed in first trimester cells. Cytochrome P450scc and its mRNA and adrenodoxin content were determined using Western blot or dot-blot techniques. Both proteins and the mRNA were detected in maternal tissue of first and second trimesters of gestation. In conclusion low P4 levels synthesized by first trimester maternal cells are not due to the absence of either cytochrome P450scc or adrenodoxin protein or production of P450scc mRNA. The data suggest that the refractoriness of the maternal caruncle cells during the first trimester is the result of post-translational regulation.


Maternal behavior and neuroendocrine regulation of suckling-mediated anovulation in cows.

Although it is clear that the initial endocrine deficit contributing to the length of the postpartum anovulatory period in suckled cows is of pituitary origin, this limitation is only operative for about the first 2 weeks of the puerperium. Thereafter, the pattern of LH secretion required for the final stages of follicular development and ovulation is blocked or attenuated through a more centrally regulated phenomenon. Hence, much of the recently published work in this area has focused on regulatory processes within the hypothalamus. This focus ignores the critical issue of exteroceptive signalling. Recent observations in this laboratory suggest that exteroceptive cues responsible for suckling-mediated anovulation are specifically attributable to the dams' own calf, but are not teat-specific. In fact, suckling does not produce an extended anovulatory state in the absence of a maternal-offspring bond. This review provides an historical perspective of investigations leading to this conclusion, and proposes a conceptual working model that links the special senses, maternal behavior and neuroendocrine centers that drive gonadotropin secretion during the puerperium.


Nutrition-endocrine interrelationships in the lactating and weaned sow.

Previous studies had identified the effects of nutrient restriction on delayed occurrence of estrus when body condition is low at farrowing or levels of intake fall below 2.5 kg (8.35 Mcal ME/h/d) during lactation. It appears that the failure via the GnRH pulse generator to stimulate sufficient LH pulsatility to trigger steroidogenesis may play a major role in the lack of reinitiation of cyclicity. Base-line concentrations, because of their variability between individual animals, may not be a major factor in predicting the time to return to estrus. Prolactin appears to be definitely antigonadotropic during lactation but may be involved in folliculogenesis effects during the postweaning period. Previous results would indicate that metabolic factors in concert with the major reproductive hormones play a key role in reestablishing the cycle postweaning. To achieve a greater understanding of the complexities of these two systems--nutrition and reproduction-greater emphasis must be placed on more precisely regulating the integral factors modulating the return to cyclic behavior.


Metabolic and reproductive hormones during lactation and the post-weaning period in sows.

There is a great variation in body weight loss during lactation among primiparous sows fed a standard diet that is adjusted based on the number of piglets nursed and the maintenance requirements. Energy and protein catabolism is more pronounced during the first 1 to 3 weeks of lactation and sows with low weight loss recover earlier from their negative energy balance during lactation than sows with high weight loss. Using continuous blood collection a decrease in plasma levels of oxytocin, prolactin, and insulin, and an increase in plasma levels and no of LH pulses during lactation were demonstrated. Prolactin levels gradually increased in response to each suckling while only 40-50% of recorded sucklings induced a significant rise in plasma oxytocin. Following a 24-h fast during lactation, levels of prolactin were very low but increased rapidly after refeeding. Even plasma levels of insulin and glucose decreased to very low levels during fasting, but the release of LH was similar before and after refeeding. Weaning resulted in decrease in plasma levels of prolactin and increase in plasma levels and no. of LH pulses. Plasma levels of cortisol showed a diurnal pattern of change which disappeared on the day of weaning. In response to weaning plasma levels of glucagon and gastrin decreased, whereas insulin and somatostatin increased. At weaning sows with low weight loss during lactation had higher plasma insulin and lower plasma cortisol levels than sows with high weight loss, but no differences in levels or no. of LH pulses were observed between the two groups of sows.


Ontogeny of gonadotropin action in the rat ovary.

Specific binding of radiolabelled FSH and LH to rat ovaries was demonstrated at the age of 7 days. However, when the biological response to LH and FSH was monitored by cAMP production in vitro, the FSH response appeared earlier than that of LH, on days 4 and 7, respectively. Cholera toxin stimulated cAMP production even in fetal ovaries, suggesting the presence of functional post-receptor machinery of cAMP production. Hence, the appearance of the functional gonadotropin receptor probably plays a key role in the onset of postnatal ovarian steroidogenesis. To test the effect of gonadotropin suppression during postnatal ovarian development, a potent GnRH antagonist was administered to neonatal animals between days 1-6 or 1-9 of life. The ovarian responsiveness to FSH developed even in the absence of normal gonadotropin levels, but that to LH was suppressed after the longer antagonist treatment. The temporal relationship between the onset of LHR gene expression, i.e. transcription, and translation to functional receptor protein was thereafter investigated using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. The measurements revealed the existence only of truncated versions of LHR mRNA in the fetal ovary from day 17 of gestation up to day 7 of postnatal life. With the onset of the receptor function around day 7, also larger mRNA transcripts, corresponding to the full-length receptor protein appeared. Our findings suggest that the LHR gene may be constitutively expressed in the ovary and a change in the alternative splicing pattern may cause the onset of translation of a functional receptor protein.


Advances in reproductive endocrinology of fish.

In teleosts two gonadotropins (GtHs) are produced: GtH I which stimulates steroidogenesis and incorporation of vitellogenin into the oocytes and GtH II, which stimulates steroidogenesis in the last stage of maturation and ovulation. Synthesis and release of GtHs are under control of gonadotropin releasing hormones, growth hormone, gonadotropin releasing inhibitory factor (GRIF)--dopamine, neuropeptide Y (NPY) gamma-aminobutyric acid (GABA) and melatonin. It was also found that calcium ions play a role of an intracellular mediator in GtH release. In ovaries, GtH stimulates production of 17 alpha-hydroxyprogesterone in the thecal cells. This steroid is transferred to granulosa cells where it is converted to 17 alpha 20 beta dihydroxy-4-pregnen-3-one (17 alpha 20 beta DHP). This steroid acts on the oocyte surface causing an appearance cytoplasmatic maturation promoting factor (MPF) which initiates the nuclear membrane breakdown and a subsequent cell division in both mitosis and meiosis. Teleosts are the only animals in which it is possible to change sex and to have population of fish of one sex. This possibility is widely applied in fisheries practice.


Extragonadal gonadotropin receptors, their distribution and function.

Luteinizing hormone (LH) and a second pituitary gonadotropin, follicle-stimulating hormone (FSH), together control steroid secretion and gamete development in both males and females. LH and its agonist human chorionic gonadotropin (hCG), share a common receptor in gonadal cells. There is increasing evidence for the existence of extraovarian LH/hCG binding sites in mammalian females. High affinity, low capacity LH/hCG receptors have been detected in pigs, rabbits and rats. Gonadotropin receptors in the human uterus were also demonstrated using immunocytochemical techniques. The presence of LH/hCG receptors, both in the endometrium and myometrium, has been so far found in pigs and humans. Receptors in the endometrium are present in glandular and luminal epithelium and stromal cells. In the myometrium, they are present in circular and longitudinal myometrial smooth muscle and vascular smooth muscle. Recently, LH/hCG receptor gene expression was confirmed both in the endometrium and myometrium of the pig. The amount of receptors is higher in the luteal phase as compared to the follicular phase of the estrous cycle indicating possible regulation of these receptors by ovarian hormones. Treatment with estradiol benzoate increased the number of LH/hCG binding sites compared with ovariectomized gilts receiving corn oil. However, administration of progesterone caused an elevation of these receptors, when compared with estradiol. Combined administration of estradiol and progesterone increased receptor capacity similar to progesterone alone. It seems that there are species differences in the uterine binding response to estradiol since the positive response to estradiol by uterine receptors in the ovariectomized pig is quite different from that observed in rabbits and rats. In the endometrium, hCG and/or LH may regulate glandular and luminal epithelial cell function via cAMP modulation or by increasing the local synthesis of steroid hormones. Stimulation of LH receptors with hCG in estrogen primed ovariectomized gilts had a quiescent effect on myometrial contractility in vitro. We examined also the effect of hCG on electromyographic activities of the uterus in ovariectomized and estrogen treated pigs. The hCG treatment caused a significant reduction of total duration of electrical activity and mean burst duration. Based on our earlier and recent results we suggest that the role of LH/hCG receptors in the myometrium is the regulation of uterine contractility, though the second messenger system remains to be elucidated.


New pathways in animal reproductive physiology frontiers and perspectives.

With the inrush of new data the recent clear division of neural, hormonal and immunological regulation has been seriously complicated. Both central and peripheral neural tissue produce over 30 neuropeptides, among which are many classic peptide hormones. A steroid biosynthetic pathway has been demonstrated in oligodendrocytes. However, the distribution and role of peptydoergic neurons within the reproductive system are only superficially known among farm animals. Neurons have receptors for many hormones and interleukins. Cells of the immune system, in addition to secretion of many interleukins and interferons, produce neuropeptides locally and they possess specific receptors for them as well. Till now, the interaction between the nervous, hormonal and immunological systems has not been taken into account while investigating the functions of ovarian follicles, the corpus luteum, oviduct and uterus. The penetration of blood and lymphatic vessels by hormones, neuropeptides and cytokins has not been taken into consideration also. The counter current transfer of many steroid and peptide hormones from ovarian venous and lymphatic effluent to arterial blood supplying the ovary and through arterial anastomoses of the oviduct and uterus has been hithero shown. It has been demonstrated that thanks to this system, arterial blood supplying the uterus and oviduct has, in physiological conditions, a much higher level of some steroid hormones such as progesterone and androstendione, 37% and 36% respectively, than in systemic blood. Recently, a powerful exchange system for resupplying hormones to the brain which is dependent on the phase of the estrous cycle, has been discovered. It has also been demonstrated that neuropeptides LH-RH, beta-endorphin and oxytocin as well as the steroid hormone progesterone, were counter current transferred from venous to arterial blood at the perihypophyseal cavernous sinus and carotid rete in sheep and gilts, but only during specific periods of reproductive activity. The mechanism of this process is still unknown. The role of peptydoergic neurons and cytokins in vascular permeability during hormone counter current transfer in the broad ligament vasculature, perihypophyseal cavernous sinus and carotid rete has not been investigated. It is suggested that progress in this area may change our point of view on many basic regulatory mechanisms involved in animal reproductive physiology.


Hormonal regulation of ovarian function in vivo and in vitro.

In the ovary steroids are produced by the follicles, corpora lutea and interstitial cells. In the follicle a substantial steroid production starts after the antrum formation and the main steroid produced is estradiol which supports folliculogenesis. Its content rises as the follicle grows. In the preovulatory period of time estradiol, released in a great amount into the circulation, triggers the ovulation inducing discharge of LH from the pituitary gland. Afterwards the follicle stops producing estradiol and androgens and starts to form progesterone. Such a swish in steroid synthesis is a universal feature for many species investigated. The results of experiments suggest that this swish is due to the inhibition of androgen production and a subsequent decline of aromatase activity. After ovulation progesterone synthesis is continued by corpus luteum (CL). The pattern of steroids produced by CL depends upon the stage of luteal phase and upon the species investigated. In the pig newly formed CL contain little steroids. The highest progesterone and androgen content is characteristic for mature and midway CL. In regressing CL progesterone and androgen concentrations drop while estradiol reaches its highest level. Steroid synthesis is modulated by gonadotropins and steroids.


Biogenic amines and the activity of the hypothalamo-pituitary-ovarian axis in ewes.

An important feature of communication between the central nervous system and the pituitary-ovarian axis is the pattern of pulsatile discharge of hypothalamic luteinizing hormone releasing hormone (LHRH). The discharge of LHRH is under control of noradrenergic, dopaminergic, and serotoninergic systems of the brain. These systems intervene between external and internal signals (e.g. photoperiod and gonadal steroids) and LHRH output. In the ewe, noradrenaline, dopamine and serotonin of the brain are implicated in the control of LHRH output, and hence luteinizing hormone (LH) release, during both the anoestrous and breeding seasons. These amines are involved in steroid-dependent and steroid-independent regulation of LHRH/LH discharge. An interplay of inhibitory versus excitatory influences of these amines on LHRH/LH release appears to govern the pattern of LHRH/LH output during the annual reproductive cycle and the ovulatory cycle. A concise overview of this topic will be provided.


Control of the LH surge mechanism in the female pig.

The functionality of the oestrogen-positive feedback mechanism is the basis for the preovulatory LH surge and thus for regular cyclic activity in the sow. The LH surge mechanism (LH SM) gradually matures as a function of age, immature gilts display delayed, low amplitude LH surges in response to oestradiol benzoate (OB). The maturation of the LH SM apparently is ovarian oestrogen-dependent. Continuous ovarian secretions, probably oestrogens, also appear to be necessary for the final peripubertal maturation of the LH SM and to maintain the functionality of this mechanism in the sexually mature gilt. Superphysiological levels of oestrogens are, however, detrimental to the development of the LH SM. Failure of various infusions of the opioid antagonist naloxone during the surge period to enhance the magnitude of OB-induced LH surges in immature gilts does not support the idea, that central opioidergic systems are of major importance in preventing mature LH surge response at this age. However, opioids could be involved in the termination of the LH surge. Experiments using the opioid agonist morphine and the antagonist naloxone to demonstrate that opioids are involved in the generation of the LH surge in the mature gilt have so far provided equivocal data. Studies using pulsatile infusions of LHRH or of a potent LHRH-agonist during the surge period in OB-treated immature gilts, in which endogenous LHRH release was blocked by methallibure, suggest that oestradiol fails to generate mature LH surges because the gonadotrophs of the immature gilt are unable to respond to enhanced LHRH secretion during the surge period in an adult-like manner. During early lactation the LH SM cannot be activated by OB, while during late lactation a partial recovery of the LH SM occurs. Minor breed differences exist in the functionality of the LH SM during lactation between LW sows and highly fertile Chinese Meishan sows, in which lactational anoestrus is not obligatory.


Central nervous system peptide and amino acid modulation of luteinizing hormone and prolactin secretion in the pig.

We recently demonstrated that pulsatile LH secretion is associated with pulsatile gonadotropin releasing hormone (GnRH) in the pig. Endogenous opioid peptide (EOP) inhibition of pulsatile LH and prolactin (PRL) secretion is dependent on reproductive status and development of this EOP system is a brain maturational process independent of the ovary. Once sexual maturation has occurred, EOP then become part of a progesterone dependent system and EOP inhibit a noradrenergic component of this system. During lactation, EOP also inhibit pulsatile LH, but stimulate PRL secretion. N-methyl-d,l-aspartate (NMA), an agonist of the excitatory amino acids (EAA), aspartate and glutamate, suppressed LH secretion in gilts pretreated with progesterone or vehicle. Both the EOP agonist, morphine (MOR), and the EOP antagonist, naloxone (NAL), delayed emergence and time to maximum serum LH concentration of the estradiol-induced LH surge in prepuberal and mature gilts, respectively. Therefore, EOP may normally have both a permissive as well as an inhibitory role in the LH surge mechanism. Although a norepinephrine synthesis inhibitor failed to alter basal PRL secretion, the PRL increase after NAL was suppressed in progesterone-treated ovariectomized (OVX) gilts. NAL suppressed the PRL response to NMA in OVX gilts pretreated with oil vehicle or progesterone, indicating that NMA stimulation of PRL secretion is mediated through the EOP system.


[The role of the pineal gland in cartesian psychophysiological doctrine].

In the present paper, we review the cartesian description of the neuromuscular reflex and the sensorial perception as well as the hypothetical role of the pineal gland on these functions. We analyze the historical bases which support the physiological cartesian doctrine and, from the perspective of our present knowledge, we evaluate the contributions of Descartes to the scientific progress of his time. In the elaborated psychophysiological theory of the french wise, the pineal gland plays a pivotal role, raising the theory that the human soul could be located within this organ.


Prenatal nicotine exposure induces cardiac adrenergic subsensitivity in adult rats.

Adult offsprings of Wistar female rats treated during pregnancy (days 1-20) with nicotine (1 mg/kg s.c.,b.i.d.), were tested in order to detect possible alterations in the reactivity of the cardiovascular system to sympathetic agonists. Dose-response curves to the pressor response of noradrenaline (NA) did not show any differences between control and experimental animals. However, cumulative dose-response curves to the chronotropic effect of NA on isolated atria were significantly shifted to the right in nicotine prenatal treated rats than in controls. Accordingly, 3H-dihydroalprenolol binding was significantly reduced in hearts of experimental animals as compared with controls, without any change in affinity. These data demonstrate long lasting deleterious effects induced by prenatal nicotine exposure, probably resulting from alterations in the sympathetic system during the developing stage.


High-protein diet: effect on insulin secretion patterns from streptozotocin-diabetic rats and mice.

In the present study we have investigated the effect of a high-protein feeding on glucose induced-insulin secretion patterns from high dose streptozotocin (SZ) injected rats and mice, and from mice given multiple low doses of SZ. For this purpose male rats and mice were fed either a high-protein, carbohydrate-free diet, or control diets, before and after i.p. injections of SZ, or citrate buffer only. Our results show that when SZ was given as a single diabetogenic dose, rats and mice kept on the high-protein diet presented lower serum glucose levels, normal basal insulin values, and higher first and second phases of stimulated insulin release, when compared with diabetic animals on control diets. Furthermore, when rats prolonged their high-protein feeding from 4 to 11 days after SZ injection, there was an additional increment in insulin secretory capacity with a further diminution in serum glucose levels. We also show that high-protein feeding in mice given multiple low doses of SZ (a model of autoimmune diabetes), produced a diminution in serum glucose values, and an improvement in both phases of stimulated insulin release. Thus, in the two models of experimental diabetes used here, high-protein feeding exerts beneficial effects in beta cell responsiveness to glucose.


Cyclic AMP infusion and blood sugar, serum insulin and serum nonesterified fatty acid responses to glucose in recent experimental hyperthyroid dogs.

Recent experimental hyperthyroid (REH) dogs exhibit poor "in vivo" insulin responses to glucose probably due to a failure somewhere in cAMP-adenylate cyclase system. The actions of exogenous cAMP on these responses and on the regulation of blood sugar (BS) and serum nonesterified fatty acids (NEFA) during glucose infusion tests (GIT) in REH and normal dogs were studied here. Hyperthyroidism was induced by 1-thyroxine administration (100 micrograms/kg body wt./die, 10 days). GIT consisted of i.v. glucose-priming followed by glucose i.v. continuous infusion (60 min). cAMP (0, 33 or 66 mg/kg body wt./min) was infused alone (30 min) and then overlapped to gluco-se infusion (60 min). Peripheral veins were used for infusions and blood sample withdrawal. BS, serum inmunoreactive insulin (IRI) and serum NEFA concentrations, basally and throughout the test, were measured. Basally, there was neither action nor interaction of hyperthyroidism and exogenous cAMP on these variables. During the GIT, the BS levels remained unaffected by hyperthyroidism; cAMP increased them, but failed to interact with hyperthyroidism. cAMP noninfused normal dogs responded to hyperglycemia with hyperinsulinemia, whereas REH dogs noninfused the nucleotide did not. cAMP administration at a high dose promoted their response in normal and REH dogs, particularly in the former; in the latter, the response was still lower than in cAMP noninfused normal controls. Although recent hyperthyroidism increased serum NEFA basal level, it exerted neither action nor interaction with the infused cAMP on serum NEFA during GIT. Results are discussed on the basis that the abolished insulin secretion "in vivo" characterizing the REH dogs, related to beta-adrenergic deficiency, can be for the most part restored by exogenous cAMP administration, despite which some glucose and triglyceride metabolism impairments are developed.


[Emergency aorto-coronary bypass after myocardial infarction].

During a recent three-year period, 37 patients had an emergent aortocoronary bypass (ACB) after evolutive acute myocardial infarction. The patients are divided up into two groups: group I includes 12 patients who were operated after the failure of early thrombolysis; group II includes 25 patients operated after the failure of revascularization through percutaneous angioplasty. In group I, all patients survived and 9 had no postoperative complications. In group II, the outcome was favorable for 16 patients. Long-lasting postoperative inotropic support was required for nine patients. Two patients died early. In all patients of the study, surgery failed to prevent myocardial necrosis but there was no recurrence of angina nor major left ventricular malfunction in the long term. This work suggests that early surgery after acute myocardial infarction may be a rescue procedure, with low risks and good long-term results.


[Can pheochromocytoma be considered a benign unilateral intra-adrenal sporadic hypertensive tumor ? Reflections on a series of 105 surgically treated subdiaphragmatic chromaffin tumors].

In a 20 year period, from 1971 through 1991, 105 chromaffin tumours--excluding cervical ones--were operated by the same surgeon: 50 during the first 15 years and 55 during the last 5 years. Pheochromocytomas are defined as intra-adrenal chromaffin tumours, and paragangliomas--or ectopic pheochromocytomas--as of extra-adrenal location. Among those tumours, 30 were malignant (i.e. metastatic) and 75 benign. Among the 30 malignant tumours, 14 were ectopic, 2 occurred in a MEN II A setting and were bilateral, 2 were associated with liver adenoma and liver hemangioma respectively suggesting Von Hippel-Lindau syndrome, and one case was associated with a seemingly sporadic primary hyperparathyroidism. 9 out of those 30 malignancies were not associated with hypertension. Among 75 benign pheochromocytomas or paragangliomas, 10 were ectopic, 7 occurred in a MEN setting (6 type II, 1 type I). 3 patients without evidence of MEN or other neuroectodermal abnormalities presented bilateral pheochromocytoma, either synchronous (2) or metachronous (1). 7 cases occurred in a Von Hippel-Lindau syndrome (3 bilateral) and 4 in a neurofibromatosis setting (1 bilateral). 3 other cases were familial without evidence of MEN (including a case of triple tumour: bilateral and ectopic and another ectopic case). 2 other cases were associated with seemingly sporadic hyperparathyroidism. As a whole, in 34 of 75 benign pheochromocytomas or paragangliomas, the tumour was not intra-adrenal, unilateral and sporadic. Among those 75 tumours, 22 were not overtly hypertensive, including 10 out of the 41 seemingly intra-adrenal, solitary and sporadic. The pheochromocytoma, benign, intra-adrenal sporadic, hypertensive accounts for no more than 30% of the subphrenic catecholamine-secretin chromaffin tumours.(ABSTRACT TRUNCATED AT 250 WORDS)


[Recurrence of cervical lymph node involvement in surgically treated thyroid cancer. Uselessness of routine cervical lymph node excision (medullary carcinoma excluded)].

From 1966 throughout September 1990, 753 patients underwent surgery for thyroid carcinoma, in the same institution, covering all pathological types. Complete follow-up was achieved in 96% of them, being at least 7 years in 50% of cases. 599 (80%) are currently alive. Neck dissection was not routinely done, except for medullary thyroid carcinoma, but rather selectively, if nodes were palpable either pre or intraoperatively, and also (since oct. 1983 i.e. the last 400 cases) if, after routine sampling of mid jugular nodes, frozen sections assessed nodal invasion. On the grounds of this policy, 205 patients underwent unilateral or bilateral neck dissection; 17% of them died during follow-up whereas 5.9% (12 cases) exhibited a cervical nodal recurrence, 6 of them occurring less than two years post-operatively, including 3 medullary thyroid carcinomas. 548 had no neck dissection; 9% died during follow-up whereas 0.9% (5 cases) exhibited a cervical nodal recurrence, 3 of them occurring less than two years post-operatively. Routine neck dissection seems not to be justified in the surgery of non medullary differentiated thyroid carcinoma, in as much as late occurrence of cervical node metastases is uncommon and does not obviously impair life-expectancy.


[Diagnostic laparoscopy. Its current indications].

Operative laparoscopy and laparoscopic surgery are quite topical today, but not so much diagnostic laparoscopy. In fact, the wide distribution and great accuracy of new noninvasive exploratory techniques has revolutionized strategy for the diagnosis of abdominal diseases. It has been said that these techniques have now superseded laparoscopy, which should be abandoned. The reply should be that, indeed, laparoscopy has lost many of its classic indications, but that it still retains other important ones. The results obtained with a very close integration of laparoscopy and ultrasonography should particularly be emphasized, as they provide a decrease in risks and an improvement of diagnoses.


[What is the role of elective surgery in diverticular sigmoiditis?].

From 1981 to 1991 inclusive, 188 operations were carried out for diverticular sigmoiditis. One hundred and thirty-nine patients were operated in emergency for acute complications (123) or fistulae (16), and another 49 had surgery scheduled outside acute crisis periods. Mortality and morbidity respectively are 16.5 and 31% in the first group, against 0 and 12% in the second one. Similarly, the stay in hospital varies from 13 days for scheduled surgery to 23 days for emergent surgery, the latter also requiring to account for risks and for the duration of a second operation that is far from exceptional (40%). Considering the severity of some evolutive complications, the authors advocate early radical surgery for symptomatic diverticular sigmoiditis, after the second crisis or as soon as the first one if it has been severe, and in young subjects and patients at risks.


[Cervical osteoid osteoma. Report of a case and review of the literature].

One case of a cervical osteoid osteoma is presented and compared with infrequent similar cases from the literature. The authors recall the diagnosis difficulties, facing a long standing not explained neck pain due to poor neurological and current radiological informations. The interest of the bone scintigraphy, CT scan and M.R.I. are emphasized. Like in other cases, the pain disappeared after surgical removal of the tumor. The eventually associated scoliosis often rectify too.


[Pancreatic metastasis of naso-sinusal epithelioma. Apropos of a case].

The authors report a pancreatic metastasis of sinusal squamous cell carcinoma in a 69 year-old man, 18 years after the first excision of the primary neoplasm. The metastases appearing in a patients having previously presented several tumors, was detected by a rising CA 19-9 level and a pancreas head enlargement at the CT. The diagnosis was identified at laparotomy by tumor biopsy. The vascular involvement of the tumor obliged to perform double bypass. 103 cases of pancreatic metastases, published in the literature from 1983 to 1991, are reviewed. Generally the pancreatic mass is visualized by CT but the diagnosis is only carried out on microscopy. Treatment depends on anatomical and pathological characteristics of primary and secondary tumours. Solitary metastasis of renal carcinoma origin have the best prognosis after radical surgery. In other cases palliative procedures are widely used. First case of pancreatic metastasis originated from recurrent sinusal squamous cell carcinoma with poly-tumoral clinical presentation.


[Arteriovenous fistula for chronic hemodialysis. 370 patients].

In cases of chronic renal failure, the usual technique for vascular approach is an arteriovenous fistula (AVF). This is the vascular approach with the longest lifetime. Microsurgery has improved the realization technique. This technique was used between 1978 and 1987 in 370 adult patients. Distal AVFs are made as a priority to preserve the patient's vascular capital. Radial AVF is the basic technique. Complications, including thrombosis, aneurysms, stenosis, low flow rate, require second surgery that must often be repeated. Arteriovenous bypass with a saphenous or cubital venous graft is used in difficult cases. Bovine carotid artery grafts are still used as bypass grafts in occasional cases; their lifetime is usually short. Catheterization through a jugular (never subclavian) site is a temporary alternative.


Effect of using soft liner on bone density around the abutments supporting complete lower overdenture.

The effect of lower acrylic overdentures lined with soft liner on bone density around the abutment was studied on 14 patients divided into two equal groups. Group I patients using lower acrylic overdenture lined with soft liner. The abutments selected in each patient were two canines and two posterior. Bone density was measured from periapical radiographs made at denture insertion and after one year of denture use, for each abutments, using an accurate densitometer. The results showed decrease in bone density in the crestal alveolar bone around the abutments through the one year study period. patient using superstructure lined with soft liner showed less bone density than those using acrylic overdenture. The results of these study reached the conclusion that the resiliency of soft liner reduces the load applied over the overdenture abutments and in turn reduces alveolar bone changes.


Durability of cermet ionomer cement conditioned in different media.

The glass ionomer cement has exhibited significant adhesion to hard tooth structures, and good cariostatic properties. The sintering of the silver alloy powder and glass ionomer cement "cermet cement" has provided additional improvement in the physical properties of the restorative material. These were flexural resistance, wear resistance, increased radio-opacity, hardness and porosity. The improvement in the physical properties of the cermet glass cements has provided an extension in their clinical use as core build up, lining for inlays, amalgam and composite restoratives, fissure filling, restoration of primary teeth, class II tunnel preparation, treatment of root caries and repair of defective metal margins in crown and inlays.


Vibration pattern of different endosonic instruments.

The history of using ultrasound in dentistry goes back to 1952. The first report on the use of ultrasound as an adjunct to mechanical debridement was given by Richman in 1957. It's popularity started with the work of Martin then many clinical evaluations were reported mainly discussing the efficiency of ultrasonics in root canal preparation.


Histochemical classification of human minor labial salivary glands according to their glycoprotein content.

There is debate about the nature of the secretory cells in human labial salivary glands. Histologically two types of acinar cells were observed. The predominant mucous acini, few basophilic serous acinar cells were detected. Histochemical differentiation of these cells according to their neutral and acidic mucopolysaccharides content using PAS, AB pH 1 and AB pH 2.5 stain revealed the presence of three types of acinar cells: 1. Cells rich in both neutral and acidic mucopolysaccharides. 2. Cells rich in either neutral or acidic mucopolysaccharides. 3. Cells contain neither neutral nor acidic mucopolysaccharides. The first type constitute the major component of the gland.


Trimetaphosphatase activity in rat incisor odontoblasts during early dentinogenesis.

The ultrastructural localization of trimetaphosphatase activity have been investigated in early stages of dentinogenesis in the rat incisor. Extracellular reactive structures were present in between the odontoblasts during early secretion and absent later on. Tubular lysosomes were observed for the first time in odontoblasts and seemed to be involved with other elements of the lysosomal system in endocytosis of extracellular substances.


Anti-inflammatory effect of natural steroid sapogenins on oral aphthous ulcers.

The search in plants for sapogenins has been stimulated by the need for readily accessible sources of sapogenins which can be converted in the laboratory to animal sterols of therapeutic importance. The present study represents a clinical trial for the investigation of the antiinflammatory effect of natural steroidal sapogenins on oral aphthous ulcers.


Occlusal vertical dimension changes in visible light-cured resin.

On a twenty standard, identical edentulous upper and lower casts, an identical upper and lower waxed-up sets of dentures were constructed with same vertical dimension of occlusion. These waxed up dentures were divided into two equal groups. For group I, the dentures sets were processed in compression molding heat-cured acrylic resin denture base material. For group II, the denture sets were processed in visible light-cured denture base material. After processing the vertical dimension of occlusion was measured for every denture set in both groups. It was found that there was an increase in the vertical dimension of occlusion on group I and a decrease in the vertical dimension of occlusion in group II. Regardless of the direction of the changes in the vertical dimension of occlusion, it was found that there was a significant difference between the dimensional changes in both groups and the dimensional changes in the denture bases of group I was more than group II by 54.5%.


Examination services provided by dental hygienists.

The information presented in this paper was obtained as part of an ongoing longitudinal study of 1982 dental hygiene graduates. This paper presents information contracted by the American Dental Hygienists' Association and includes information on examination services provided to new and recall, child and adult dental hygiene patients by dental hygienists. Mail questionnaires were sent to a cohort of 1,008 dental hygienists who graduated in 1982. Data presented here were collected in September 1986. Surveys were returned from 766 subjects, 77% of those with valid addresses. Of the respondents, 455 were working in traditional clinical dental hygiene positions and provided information on patient examination services. The frequencies reported for the 15 examination services investigated by the dental hygienists varied for child and adult patients and for new and recall patients. Visual gingival examination was the most frequently provided service. In conclusion, dental hygienists need to incorporate additional patient examination services into their diagnostic workups to ensure adequate patient care and to provide adequate information to evaluate their dental hygiene care.


A new neutralization method for influenza virus in cell culture.

A novel neutralization method (ELISA-NT) has been developed for simple detection of neutralizing antibodies to influenza virus in which type specific soluble (S) CF antigen produced by unneutralized virus was measured by anti-S immune (probe) serum and enzyme-labelled Clq. Neutralizing antibody activity was determined within 48 h and expressed as a new term, NT% of the quantity of neutralized virus. A good correlation was found between NT% determined by the ELISA-NT method and NT titer by the conventional method in 82 human serum samples (r = 0.941 for type A and r = 0.875 for type B of influenza virus, p < 0.01).


Cytotoxic effects of antitumor agents on mouse tracheal organ cultures at ultrastructural level.

A cytotoxic effect of antitumor agents (mitomycin C;MMC, adriamycin;ADM, bleomycin;BLM, 5-fluorouracil;5-FU, and cisplatin;CDDP) on ciliated epithelial cells of mouse tracheal organ cultures was studied in transmission electron microscopy. Mouse tracheal rings incubated with each agent in a concentration of 1 microgram/ml or 10 micrograms/ml were observed after 1, 2, and 20 hr of the incubation. After 2 hr, the ciliated epithelial with MMC or ADM of 1 microgram/ml exhibited appearance of lipid droplets in the nonciliated cells and the swelling of mitochondria and epithelial cells. Further incubation of 20 hr with those agents resulted in the pronounced degeneration including the ciliary subsidence into intracellular spaces, balloon-like ciliary swelling, and cellular destruction. Whereas, the ciliated epithelia with 5-Fu, BLM or CDDP did not show any notable change within 2 hr. After 20 hr, these exhibited the swelling of mitochondria, cilia and epithelial cells. The ciliated epithelia incubated with MMC or ADM of a greater concentration of 10 micrograms/ml showed remarkable cytotoxic effects after 1 hr of the incubation. The morphological changes in the epithelial cells with 1 hr incubation were almost similar to those of 20 hr incubation with the 1 microgram/ml. After 20 hr, the cellular degeneration proceeded to extremely flattened epithelial cells with disappearance of cilia and appearance of numerous vacuoles. Those with 5-FU, BLM or CDDP of 10 micrograms/ml exhibited ciliary swelling after 2 hr, but the morphological changes of 5-FU were more remarkable than those of BLM or CDDP. After 20 hr, the pronounced degeneration was observed, and it was similar to one of MMC or ADM of 2 hr incubation.


Suppression of 125I-uptake in mouse thyroid by seaweed feeding: possible preventative effect of dietary seaweed on internal radiation injury of the thyroid by radioactive iodine.

We conducted an animal experiment to determine how dietary seaweeds rich in iodine and dietary fibers suppress radioactive iodine uptake by the thyroid, using mice and four kinds of experimental diets, three with 1% or 2% powdered fronds of the kelp Laminaria religiosa and 2% powdered laver Porphyra yezoensis, and one with cellulose. Iodine content of a hot-water extract of the kelp was 0.530 +/- 0.001%, and its dietary fiber (DF) values were 52.8 +/- 1.2%. Iodine in an extract of the laver was 0.008 +/- 0.001%, and its DF values were 41.4% +/- 0.7%. A statistically significant reduction of 125I uptake by the thyroid, 3 hours after intragastric administration of the radionuclide at a dosage of 18.5 kBq or 185 kBq in 0.3 ml aqueous solution per mouse, was observed in mice previously fed the experimental diets containing 1% and 2% kelp during periods varying from 24 hours to 7 days. The degree of the suppression was observed to depend on the amount of iodine in the diet or in the injected sample, no matter whether organic or inorganic, judging from the results of an additional experiment. Thus, we conclude that previously fed iodine-rich material, especially dietary seaweeds rich in iodine and other minerals, vitamins, and beta-carotene, such as kelps or laver supplemented with inorganic iodine, may be effective in prevention of internal radiation injury of the thyroid.


Oxygen-independent antimicrobial activity against Salmonella enteritidis of specially activated macrophage with living vaccine.

Characteristics of peritoneal macrophages recovered from mice infected with two attenuated strains SER and Jena of Salmonella enteritidis were compared. Strong resistance against lethal infection with a virulent strain 116-54 of S. enteritidis was seen in a group of mice immunized with strain SER, but not in a group of mice immunized with strain Jena as well as in a control group. Peritoneal macrophages from mice immunized with strain SER showed an enhanced Salmonella-killing activity, an increased generation of O2- and an increased expression of Ia antigen on 7 to 14 days after infection when compared with those from mice immunized with strain Jena and thioglycollate(TG)-elicited macrophages as a control. The bacterial number of strain Jena in organs decreased more rapidly than that of strain SER after day 4 of infection. These observations suggest that the survival of an attenuated Salmonella bacilli at reticulo-endothelium is essential to increase of their activities of macrophages. Macrophages from mice injected with recombinant interferon(IFN)-gamma for 3 days induced the activated stage of the same characteristics as noted in activated macrophages from mice immunized with strain SER. Effect of oxygen intermediates (OI) scavengers such as superoxide dismutase and catalase on Salmonella-killing activity of activated macrophages was not seen at all. These results suggest that an increased generation of OI may be not primarily responsible for the ability to inhibit the intracellular growth of a virulent strain of S. enteritidis in macrophages activated by immunization with live, attenuated strains and injection with rIFN-gamma.


Effect of short-term fasting treatment on liver and renal function.

Five healthy male adults were deprived of food for a short period (40 hr) and biochemical studies and urinalyses were done before and after fasting to determine the effects on liver and renal functions. Acceleration in lipid metabolism was seen with an increase of about 90% in NEFA and about 20% in TG. GOT, GPT and LDH showed elevations of about 40 to 100% indicating a slight effect of 40 hr fasting on liver functions. BUN, HDL-C and ALP showed increases of about 30% while, CPK and TC showed decreases of about 20%. In the other parameters changes of about 10% were seen. After a fasting with water intake of about 1,000 ml/day, a body weight loss of 1.2 kg was observed at 40 hr. During the short-term fasting (40 hr) as done in our study, changes were seen in glucose and lipid metabolism. However, since no abnormalities were seen in general biochemical parameters, we consider that a fasting of this duration is valuable for use as one of the fastings.


Role of lipid peroxidation and antioxidants in aging process and thalassemia.

Oxygen free radicals and other oxygen derived species (Superoxide, O2-; Hydroperoxide, HOO; Singlet oxygen, 1O2-; Hydroxyl radical, OH; and Hydrogen peroxide, H2O2) including lipid peroxides have been suggested as important causative agents of aging and several human diseases, including cancer, multiple sclerosis, Parkinson's disease, autoimmune disease, ischemia, anemia, senile dementia, asbestosis and in thalassemia. This paper aims to communicate some of the theories and rationales in aging process and thalassemia.


Physical characteristics of an enclosed afferent reservoir breathing system.

We have assessed the characteristics of the Ohmeda Enclosed Afferent Reservoir Breathing System (EAR) using simulated spontaneous ventilation and controlled ventilation. The additional work of breathing through the system was measured and shown to be comparable to that of a modified Mapleson D breathing system (Bain) for fresh gas flows producing similar end-tidal carbon dioxide concentrations. It was shown under conditions of simulated controlled ventilation that end-tidal gas concentration was relatively insensitive to variations in inspired to expired ratio (I: E), tidal volume (VT) and deadspace (VD). Measurement of the volume of carbon dioxide rebreathed using simulated spontaneous ventilation led to the prediction that rebreathing of carbon dioxide would begin to occur in the EAR when fresh gas flow to total ventilation ratio (VF: VE) was approximately 0.87. However, comparison of the results of model lung tests and clinical data suggests that great caution should be taken in extrapolating such results into clinical advice.


Incommensurate oxygen consumption in response to maximal oxygen availability predicts postinjury multiple organ failure.

Untreated flow-dependent oxygen consumption (VO2) has recently been implicated as an unrecognized risk factor for multiple organ failure (MOF). We therefore prospectively studied 39 severely injured patients with known risk factors for multiple organ failure who were subjected to an established resuscitation protocol aimed at maximizing oxygen delivery (DO2 greater than 600 mL/min.m2) to attain a VO2 goal of greater than 150 mL/min.m2. Fifteen (38%) of these high risk patients did not meet this VO2 goal by 12 hours. These nonresponding patients had significantly elevated lactate levels, suggesting defective aerobic metabolism. Of note, this blunted VO2 response despite maximal efforts to enhance peripheral oxygen availability predicted MOF. These data serve to re-emphasize the importance of the initial shock insult in causing or priming the host for the development of late MOF.


Empty sella resulting from the spontaneous resolution of a pituitary macroadenoma.

Recent studies suggest that the infarction of a pituitary adenoma may be a frequent cause of an empty sella turcica. However, to date, evidence of such progression has been largely speculative. We present the case of a patient with a pituitary macroadenoma that underwent spontaneous involution resulting in an empty sella, as documented by serial magnetic resonance imaging scans. A brief review of the proposed causes of primary empty sella, with emphasis on pituitary necrosis, is provided.


Use of an antibiotic-bonded graft for in situ reconstruction after prosthetic graft infections.

We have developed an infection resistant vascular prosthesis by bonding rifampin to Dacron grafts with the use of a collagen matrix release system. The purpose of this study was to determine the efficacy of this antibiotic-bonded graft in resisting infection after an in situ reconstruction of a previously infected prosthetic bypass. Eighty-three adult mongrel dogs underwent implantation of a 3 cm untreated Dacron graft into the infrarenal aorta. This initial graft was deliberately infected, at the time of operation, with 10(2) organisms of Staphylococcus aureus by direct inoculation. One week later, the dogs were reexplored, the retroperitoneum debrided, and the animals randomized to undergo an end-to-end in situ graft replacement with either one of two types of prosthetic grafts: group I (collagen, n = 36) received control collagen-impregnated knitted Dacron grafts; group II (rifampin, n = 47) received experimental collagen-rifampin-bonded Dacron grafts. Each group of animals was then subdivided to receive one of four treatment protocols: (a) no antibiotic therapy, (b) cephalosporin peritoneal irrigation solution (cefazolin 500 mg/1000 ml) during operation and two doses of cephalosporin (cefazolin, 500 mg intramuscularly) postoperatively, (c) treatment as in protocol group b plus 1 week of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily), and (d) treatment as in protocol group b plus 2 weeks of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily). All grafts were sterilely removed between 3 and 4 weeks after implantation. There were no anastomotic disruptions and all grafts were patent at the time of removal.(ABSTRACT TRUNCATED AT 250 WORDS)


Coronary-prone behaviour pattern and myocardial infarction.

Seventy five patients with acute myocardial infarction (MI) and forty matched control subjects were assessed for coronary-prone behaviour pattern by a self administered scale. Analysis of the results showed a higher incidence (P < 0.001) of type A behaviour pattern in acute (MI) patients, as compared to controls.


A case of human chimerism detected by unbalanced chromosomal translocation.

Chimerism in humans is usually found only because of discrepancies in unique blood group typing or sex chromosome complements. We describe a case found because of an inherited chromosomal translocation. A female carrier of the balanced reciprocal translocation t(14;20)(q31;q13.3) had a twin pregnancy. After birth the B-twin, a girl, was found to have the balanced translocation. The A-twin, a severely malformed and stillborn boy, had two different karyotypes; a normal 46,XY and an unbalanced translocation derivative 46,XY,-14, +der(14)t(14;20)(q31;q13.3). He was a dispermic chimera, formed by two fertilized oocytes.


Prognosis of sarcoidosis. An unresolved issue.

Prognosis of sarcoidosis may be difficult to establish because the disease may follow an unpredictable course. It depends mainly on the persistence of activity over time and on the type of organ involved and its degree of functional impairment. It would be very useful for clinicians to be able to identify at diagnosis which factors would predict the final outcome of the disease. Multivariate statistical models are proposed in order to study factors influencing the persistence of activity as one of the best methods of studying the prognosis of sarcoidosis.


High resolution computed tomography in sarcoidosis and extrinsic allergic alveolitis: imaging insights.

Chest radiography gives a useful but imprecise indication of the extent of diffuse lung disease. The limitations in sensitivity and specificity of chest radiography in this context are well known and have been reinforced with the advent of computed tomography and its application to this difficult diagnostic area. High resolution computed tomography shows morphological detail invisible on chest radiography and both sensitivity and specificity in diffuse lung disease are greatly improved with this technique. Features of sarcoidosis and extrinsic allergic alveolitis revealed by high resolution computed tomography are examined in this review.


Tumour necrosis factor production by alveolar macrophages in pulmonary sarcoidosis and tuberculosis.

Tumour Necrosis Factor alpha (TNF/Cachectin) is a cytokine produced mainly by macrophages, which has been shown to cause endothelial cell damage, pyrexia and weight loss, clinical features of tuberculosis, but not of sarcoidosis which is in many other respects a similar disease. 1,25 di-hydroxy Vitamin D and gamma interferon, factors which are present in vivo in both tuberculosis and sarcoidosis, enhance the ability of macrophages to release TNF in vitro. We have studied the ability of pulmonary alveolar macrophages (PAM) harvested by broncho-alveolar lavage (BAL) to produce TNF in response to stimulation with E. coli endotoxin lipopolysaccharide (LPS). 25 patients undergoing bronchoscopy and BAL were studied: 9 with sarcoidosis, 7 with tuberculosis (TB) and 9 (non-neoplastic) disease controls. TNF was assayed by Enzyme Linked Immunosorbent Assay (ELISA) in lavage fluid and cell culture supernatants. No TNF was detected in lavage fluid from any of the groups. PAMs from control patients released no detectable TNF spontaneously, but released 59 +/- 31 units after LPS stimulation. Cells from patients with sarcoidosis and tuberculosis released TNF spontaneously in vitro (TB 226 +/- 106 units; Sarcoidosis 293 +/- 176). TNF release by these cells was not increased further by addition of an optimal concentration of LPS. Thus, the pulmonary macrophages of patients with sarcoidosis and tuberculosis released significantly more TNF than those of controls.


Bronchopulmonary lavage (BAL). A window of the lungs.

Bronchopulmonary lavage (BAL) has provided a fresh dimension for the investigation of pulmonary and multisystem disorders. BAL fluid may be analysed for cells and chemical mediators in the diagnosis and also serially for the management of several granulomatous disorders including sarcoidosis, extrinsic allergic alveolitis, chronic beryllium disease, talc granulomatosis, tuberculosis, Langerhans' histiocytosis-x and Crohn's disease. It may also provide information in fibrosing alveolitis, collagen vascular disease, occupational and drug-induced lung disease, acquired immune deficiency syndrome, bronchial asthma, neoplasia, transplantation, pulmonary alveolar proteinosis and eosinophilic lung disease. This survey analyses the value of BAL and how it has provided a new window for the chest physician.


Monoclonal antibodies to epithelioid cells in lip biopsy in sarcoidosis.

The phenotype of infiltrating and residual cells in biopsies of minor salivary glands from patients with sarcoidosis and from normal controls, were studied using a sensitive two-step indirect immunoperoxidase technique. We found that infiltrating lymphocytes were practically absent from salivary gland biopsies in the control group, but that in the Sarcoid group the numerous infiltrating lymphocytes consisted mainly of T-lymphocytes, mostly T-helper cells (CD4+ cells). These data correlate positively with other studies on lymphocytic infiltration in other organs involved in the immunopathology of sarcoidosis, e.g. the lung. In our study the glandular epithelial cells in the salivary gland biopsies were HLA-DR positive in the patients with sarcoidosis, especially in those specimens from patients with active disease in which 50-80% of the epithelial cells expressed an HLA-DR antigen. We observed a positive relationship between HLA-DR positive epithelial cells, the expression of interleukin-2 receptors (IL-2R) and the density of lymphocytic infiltrates. This is in accordance with other chronic, lymphocytic infiltratory diseases with HLA-DR positive epithelial expression, such as Sjögren's syndrome involving salivary glands. This suggests that there might be a common denominator causing disease in these cases.


High frequency of IgM antibodies to coxsackie B virus in sarcoidosis patients and patients with asbestos-related lesions.

By using radioimmunoassay (RIA) for detection of IgM antibodies to Coxsackie B viruses (CBV), the occurrence of these antibodies was investigated in patients with sarcoidosis and asbestos-related lesions. Sixty-one per cent of the patients with sarcoidosis, all patients with benign asbestos pleural effusion, and 67% of those with diffuse asbestos-related pleural thickening showed CBV-IgM. Patients with healed sarcoidosis or pleural plaques were all negative, and among the "healthy" controls seven per cent had CBV-IgM. Thus, there was a high frequency of CBV-IgM in patients with sarcoidosis and in those with asbestos-related diseases. Since the titres could be the effect of an unspecific polyclonal stimulation of the B cells, sera were tested for antibodies to rubella and cytomegalovirus, but without any remarkable results.


Lymphocytic alveolitis and airway responsiveness in recently diagnosed sarcoidosis.

We looked at the relationship between the intensity of the lymphocytic alveolitis and airway responsiveness to methacholine, in patients with recently diagnosed untreated pulmonary sarcoidosis. We studied 19 subjects, 13 M and 6 F, aged 19-58 (mean: 36.6) who had a diagnosis of pulmonary sarcoidosis within the last 6 months (radiologic stages: I, 10 subjects; II, 8; III, 1). One subject had a previous history of asthma but was currently asymptomatic. Five were smokers, 5 ex-smokers and 9 non-smokers. Initial assessment included a flexible bronchoscopy with bronchoalveolar lavage (BAL), measurement of expiratory flows, lung volumes, CO diffusion and a methacholine inhalation test. Pulmonary function tests were repeated six months later, and a second evaluation of airway responsiveness to methacholine was obtained in 13 patients. Mean % of lymphocytes, neutrophils and macrophages on BAL were respectively: 25.4, 2.3 and 72.4. Mean % of predicted values for FVC, FEV1, FEF25-75%, TLC, FRC and DLCO were respectively 91.3, 94.3, 88.8, 97.6, 102.1 and 91.2. In all subjects FEV1 was > or = 80% and PC20 was in the normal range (> 16 mg/ml in all subjects but one who had a PC20 of 12.0). There was no correlation between the % of BAL lymphocytes and the initial PC20. At 6 months, overall airway responsiveness was unchanged (geometric mean initial/6 month PC20 methacholine: 95.9/102.8) whether or not the subjects had a high intensity alveolitis (defined as > or = 30% lymphocytes on BAL).(ABSTRACT TRUNCATED AT 250 WORDS)


B-lymphocyte response in peripheral blood of patients with pulmonary sarcoidosis.

Sarcoidosis is a granulomatous disorder which can be characterized by various immunologic abnormalities including lymphocyte dysfunctions. The purpose of this study was to investigate the B-lymphocyte reactivity in the peripheral blood of 29 various patients with pulmonary sarcoidosis. A significant decrease in the production of IgG, IgM and IgA in supernatants of cultivated sarcoidosis B-cells both after stimulation with a T-cell dependent polyclonal B-cell activator (pokeweed mitogen) and with a T-cell independent polyclonal B-lymphocyte activator (Klebsiella pneumoniae) was seen, which suggested a disturbance in the B-cell differentiation of sarcoidosis patients. Those patients which were known to have a clinically active disease or a high intensity alveolitis in the bronchoalveolar lavage fluid showed a greater reduction in the B-cell differentiation response. Further evaluation of Ig-G subclasses displayed a significant decrease in the secretion of IgG1, IgG3 and IgG4. In contrast to the differentiation, the proliferation response of sarcoidotic peripheral blood lymphocytes to different mitogens did not differ from healthy controls.


Angiotensin-converting enzyme in bronchoalveolar lavage fluid in sarcoidosis.

This is the first Australian study of angiotensin converting enzyme (ACE) in bronchoalveolar lavage fluid in 51 patients with sarcoidosis. The aim was: 1) to establish the range of lavage ACE in healthy smokers and non-smoking patients with sarcoidosis. 2) to evaluate the clinical usefulness of lavage ACE. Seventeen control subjects and 51 sarcoid patients all underwent bronchoalveolar lavage, the latter also having 67Gallium scan, spirometry and carbon monoxide uptake. Eighteen patients had all tests repeated six months later. Lavage ACE was significantly higher in sarcoid non-smokers than control non-smokers (p < 0.05). In the 51 sarcoid patients, lavage ACE/albumin ratios were 10-fold higher than serum ACE/albumin ratios (p < 0.0001). In sarcoid patients with raised intrathoracic 67Gallium uptake, lavage ACE was significantly higher than those patients with normal uptake (p < 0.05). Expressing lavage ACE as ACE/albumin ratios reduced the statistical significance of correlations with other parameters, eg, lavage % lymphocytes, and lavage IgG. Lavage ACE levels changed concordantly with lung function 67Gallium scan and lavage lymphocytes, albumin and IgG. However, the wide distribution of lavage ACE in control and sarcoid subjects and the influence of smoking history severely limits its clinical application.


Idiopathic granulomatous bronchitis. An unusual form of known granulomatous lung diseases or an unknown disease?

We describe two patients demonstrating a granulomatous inflammation of bronchial mucosa characterized clinically by a persistent dry cough, lack of manifestations of bronchial asthma, normal level of serum IgE and serum ACE, inflamed bronchial mucosal appearance consisting of edema, erythema, bleeding and narrowing and recovering without specific treatment. Histopathological findings of the bronchial inflammation of our patients were characterized by noncaseating granuloma formation consisting of epithelioid cells and multinucleated giant cells with infiltration of lymphocytes, plasma cells and eosinophils. The bronchial granulomatous inflammation of our patients was thought to differ from that of diseases which have been known, to our knowledge, as diseases demonstrating a granulomatous inflammation of bronchial mucosa. Although the pathogenesis of the disease could not be clarified by a careful search of special staining and culturing for the infective agent, it was most suggestive of non-specific inflammation with a granulomatous response to some sort of inhaled agents.


Diffuse panbronchiolitis observed in an Italian male.

We describe a case of a 43 year old man who presented with productive cough, dyspnea, severe obstructive ventilatory failure and diffuse micronodular shadows on chest roentgenogram. Bronchoalveolar lavage fluid analysis showed an increased total cellularity sustained by a huge neutrophilia. Sweat test was negative. Transbronchial lung biopsy and autopsy showed unit lesion of diffuse panbronchiolitis. This report represents, to the best of our knowledge, the first case of diffuse panbronchiolitis observed in Europe.


Monoclonal gammopathy of undetermined significance in sarcoidosis. Two case reports.

We report the first two cases of monoclonal gammopathy of undetermined significance associated with sarcoidosis. Both of our patients had biopsy proven sarcoidosis with elevated proteins. Further workup of sarcoidosis patients with elevated proteins is recommended to diagnosis monoclonal gammopathy.


Is sarcoidosis related to exposure to pets or the housing conditions? A case-referent study.

On the assumption that sarcoidosis could be caused by inhalation of antigens stemming from pets a case-referent study was set up to examine this idea. Thirty-nine patients with biopsy-proven sarcoidosis were compared with 106 sex- and age-matched control persons on the exposure to pets, present and previous, in the households. In addition data on basic housing conditions and smoking habits were collected. No statistical difference in the absolute frequency of dogs, dogs and/or cats or any pet in the two groups was observed counting only pets kept for more than 2 years prior to the year of diagnosis. Equally the basic housing conditions (size, type of and age of dwelling, family size) were identical. There was a tendency of more non-smokers in the sarcoidosis group (46% vs 33%) but the difference did not reach statistical significance. However it cannot be excluded that inhalable antigens stemming from pets initiate sarcoidosis among susceptible individuals.