The significance of coasting duration during ovarian stimulation for conception in assisted fertilization cycles

BACKGROUND: Withholding gonadotrophin administration and postponing HCG injection, termed coasting, has been suggested as a treatment modality in cases of impending ovarian hyperstimulation syndrome (OHSS). It presents an opportunity to reduce the risk of OHSS and salvage the treatment, without apparent compromise to outcome. However, the duration of the coasting period, which would maintain the advantage without reducing conception rate, has not been fully established. In this retrospective study, we attempted to define the optimal interval of coasting in patients at risk of developing OHSS. METHODS: Patients were grouped according to the number of days elapsed between cessation of gonadotrophins and administration of HCG. Overall, out of 207 patients (mean age 30.76 +/- 0.33 years) coasting lasted 1 day in 39 cycles (18.8%), 2 days in 61 cycles (29.4%), 3 days in 49 cycles (23.6%) and > or = 4 days in the remaining 58 cycles (28.5%). RESULTS: There was no difference between the groups in patients' age, serum estradiol concentrations at the time of HCG administration, oocyte maturity, fertilization and embryo cleavage rates. However, patients in whom coasting lasted > or = 4 days had significantly reduced implantation (10.5%) and pregnancy (26.7%) rates compared with patients with a shorter coasting interval (ranges 18.4-27.9 and 41-55.7% respectively; P < 0.05). CONCLUSION: Coasting for >3 days appears to reduce implantation and pregnancy rates while in-vitro oocyte and embryo quality do not appear to be affected. We suggest that in patients who need coasting for >3 days, cryopreservation of embryos should be considered.     

Serodiagnosis of tuberculosis and leprosy by enzyme immunoassay

Objective: To evaluate the use of serodiagnosis for tuberculosis and leprosy using mycobacterial antigen 38 kDa, with kits from Omega laboratories, to detect IgG by enzyme immunoassay (EIA).
Method: The study population consisted of 58 patients with evidence of tuberculous infection (culture of Mycobacterium tuberculosis complex or microscopic evidence), of whom 23 had pulmonary and 35 had extrapulmonary disease. There were six subjects who had recently been treated for tuberculosis, 11 patients on treatment for leprosy and 137 patients suspected of having tuberculosis on clinical or radiologic grounds (without laboratory evidence). A control group comprised 35 healthy individuals or patients suffering from diseases other than tuberculosis.
Results: The tests showed that there was a significant difference in antibody levels between the patients with active pulmonary disease, extrapulmonary tuberculosis and leprosy in comparison with the control group ( p <0.001). The sensitivities of the two tests together for proven pulmonary tuberculosis were 100% and 95.7% at 1.0–1.5 and >1.6 EIA cut-off points respectively, while the specificities were 88.5% and 100% at the same cut-off points. The sensitivities for extrapulmonary tuberculosis were 71.4% and only 51.4% at 1.0–1.5 and >1.6 EIA cut-off points. The test was positive in 30 (21.9%) of the 137 suspected patients, while 43 (31.4%) had an equivocal result and the remaining 64 (47.7%) suspects were definitely negative. There was again a significant difference in positivity rates between suspects and the control group.
Conclusions: Omega IgG test is useful in the serodiagnosis of active pulmonary tuberculosis and leprosy, but less sensitive in extrapulmonary disease, particularly in children. Equivocal results may only add to the evidence of tuberculosis in early or minimal disease.     

Effects of mast cell-macrophage interactions on the production of collagenolytic enzymes by metastatic tumor cells and tumor-derived and stromal fibroblasts

Histological examination of the metastatic rat mammary adenocarcinoma line MTLn3 showed that macrophages and mast cells were frequently localized at the tumor periphery in the stromal tissues adjacent to the zones of tumor invasion. The interactions of these host cells with tumor cells and tumor-associated fibroblasts could be important in stimulating the production of extracellular matrix-degrading enzymes that facilitate tumor invasion and metastatic spread. Therefore, we examined the effects of isolated, activated macrophages and mast cells on the secretion of collagenolytic activities by normal fibroblasts, metastatic mammary adenocarcinoma cells and tumor-associated fibroblasts. Medium from activated macrophages or degranulated mast cells stimulated significant increases in production of collagenolytic activities by normal and tumor-associated fibroblasts and MTLn3 tumor cells. Medium from activated macrophages that had been pretreated with medium from degranulated mast cells, however, were less stimulatory to fibroblasts and tumor cell production of collagenolytic activities than medium from degranulated mast cells alone. We also examined the effects of two cytokines, interleukin-1 and tumor necrosis factor-a on activated macrophage- and degranulated mast cell-stimulation of fibroblast and tumor cell collagenolytic activities. The two cytokines alone or in combination stimulated increased production of collagenolytic activities by fibroblasts and tumor cells. Addition of the cytokines to degranulated mast cell products resulted in secretion of higher collagenolytic enzyme activities by normal fibroblasts (but not by tumor-derived fibroblasts or tumor cells) than with degranulated mast cell product-treatment of either target cell alone. Cytokines used in combination with macrophage-conditioned medium were less effective in stimulating fibroblast and tumor cell collagenase activities than cytokines alone. Thus normal infiltrating host cells such as macrophages and mast cells can have profound effects on the production of degradative enzymes by tumor cells and tumor-associated stromal fibroblasts.     

Relationship between Pollen Counts and Weather Variables in East-Mediterranean Coast of Turkey

BACKGROUND: Aeroallergen sampling provides information regarding the onset, duration and severity of the pollen season that clinicians use to guide allergen selection for skin testing and treatment. OBJECTIVES: This atmospheric survey reports (1) airborne pollen contributions in Adana in one-year period (2) pollen onset, duration and peak level (3) the relationship between airborne pollen and selected meteorological variables and; (4) effects on symptoms in pollen allergic children. METHODS: Pollen sampling was performed with a volumetric Burkard Spore Trap. Meteorological data were measured daily from April 2001 to April 2002. Asthma symptom scores were investigated in 186 pollen allergic children that were on follow up in pediatric allergy outpatient clinics during same period. RESULTS: Average measurements included 82.5% tree pollen, 7.7% grass pollen and 9.8% herb pollen 54 taxa were identified during one year. The most prominent tree pollens were Cupressaceae, Eucalyptus and Pinus. The most common herb was Chenopodiaceae pollen family. When airborne pollen levels were examined in relation to single meteorological conditions; daily variations in total pollen counts were not significantly correlated with any variable studied (humidity, rainfall, temperature and wind) (p > 0.05). On the other hand, statistically significant relationship between pollen concentration and symptom scores were found (p > 0.05). Positive correlations were seen between both Gramineae and Herb pollen, and humidity and rainfall from March to July. However, positive correlations were detected between tree pollen counts and temperature and humidity in May and June. CONCLUSION: This survey is the first volumetric airborne pollen analysis conducted in the survey area in Adana. This study suggested that the effects of weather on pollen count and symptom scores in this population could not be clearly identified with the evaluation of one-year data. However, pollen counts had effect on allergic symptoms in pollen allergic children. Examination of the complex interaction of multiple whether parameters would perhaps more fully elucidate the relationship between meteorology and aerobiology and provide the clinician with information necessary to forecast pollen prevalence. An awareness of the ever chancing, local aeroallergen patterns requires regular monitoring. Such awareness serves as a useful guide in the effective testing and treatment of atopic patients.     

Prevention of oral mucositis due to 5-fluorouracil treatment with oral cryotherapy

INTRODUCTION: One of the most common and important side effects of 5-fluorouracil (5-FU) is mucositis with ulcerations in the oral cavity. We investigated the effects of local cryotherapy on mucositis incidence administrated durng 5-FU treatment. METHODS: In a total of 99 courses, 5-FU and folinic acid combination chemotherapy was given to 40 patients. In our study, we considered every course as a single case, and cryotherapy was given to the same patient in one course but not given in the next. RESULTS: While mucositis developed in 6.7% of the courses given with cryotherapy, this ratio was 38.9% in courses given without cryotherapy. In the logistic regression analysis, development of mucositis had been found to correlate only with cryotherapy. Odds ratio (OR) = 11.5; in the 95% confidence interval (CI) = 3.2 - 41.9; (p = 0.001). DISCUSSION: Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. We concluded that oral cooling prevents 5-FU induced mucositis. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis.     

Survival rates during the first trimester of multiple gestations achieved by ICSI: a report of 1448 consecutive multiples

BACKGROUND: The purpose of this study was to determine the rate of spontaneous gestational sac loss during the first trimester in women achieving multiple pregnancies by ICSI. METHODS: A retrospective analysis was performed of 1448 consecutive multiple pregnancies conceived by ICSI. RESULTS: Of the cohort of 1448 pregnancies, twin gestations constituted 59.6% (864), triplets 30.2% (438) and quadruplets 10.0% (146). During the first trimester, 69 (4.7%) patients miscarried, while 179 (12.3%) continued their pregnancies and had fewer gestational sacs at the end of the first trimester than at the beginning. The overall loss rate of any gestational sac during the first trimester in these multiple pregnancies was 10.1%. There was a significant difference in the frequency of spontaneous reduction to twin or singleton pregnancies in the first trimester between women carrying triplets (11.7%) and those carrying quadruplets (3.5%) [P = 0.004; odds ratio (OR) 3.5; 95% confidence interval (CI) 1.3-9.1]. The frequency of gestational sac loss was significantly greater among women >35 years old (20.9%) than in women less than 35 years old (15.9%) (P = 0.03; OR 1.4; 95% CI 1.0-1.9). CONCLUSION: In multiple pregnancies there is a significant risk of spontaneous loss of any embryo during the first trimester. These findings should be considered prior to any decision about selective embryo reduction.     

Increased Expression of Fas Ligand on Mycobacterium tuberculosis Infected Macrophages: A Potential Novel Mechanism of Immune Evasion by Mycobacterium tuberculosis?

We have studied the location and mechanism of apoptosis within the granulomas in the lungs at various stages of slowly progressive primary murine Mycobacterium tuberculosis infection. Parallel sections were analyzed for detection of mycobacterial antigens, Fas, and Fas ligand (FasL) by immunohistochemistry, and for apoptotic cells by terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. The frequency of apoptosis was high in the macrophage aggregates as compared to the lymphocyte aggregates and at the interface between them. Five to seven percent of the vacuolated macrophages in the granulomas expressed FasL intensely. These cells contained large amounts of mycobacterial antigens. These findings suggest that M. tuberculosis infection can induce increased expression of FasL in a population of infected macrophages. As a consequence the infected macrophages will be protected from the attack of cytotoxic T cells and activation of bactericidal mechanisms by Th1 type lymphocytes. This constitutes a novel evasion mechanism for M. tuberculosis possibly explaining the chronic course of infection.     

Acceleration of rat brain beta-adrenoceptor subsensitivity following the coadministration of histamine receptor antagonists with imipramine

Systemic administration of isoprenaline to rats produced a dose-dependent increase in water drinking which was effectively blocked by propranolol. This dipsogenic effect was significantly inhibited by the subacute (4 days) administration of imipramine (18.1. mg/kg/day) together with either the H₁-histamine receptor antagonist, chlorpheniramine (0.1 or 1.32 mg/kg/day), or the H₂-histamine antagonist, cimetidine (1.91 mg/kg/day) or ranitidine (0.60 or 1.51 mg/kg/day). The oral subacute administration of imipramine alone had no significant effect on this behavior. However, chronic ingestion of imipramine alone (21 days) caused a significant reduction in the isoprenaline-induced behavior.It is concluded that the desensitization of central beta-adrenoceptors, as evidenced by inhibition of isoprenaline-induced drinking, can be accelerated following the oral subacute co-administration of imipramine with either H₁- or H₂-histamine receptor antagonists. It also seems that central histamine receptors may partially contribute towards the mechanism of antidepressant effect of imipramine.     

Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99

Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunization with myelin basic protein (MBP) and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the MBP amino acid sequences 68-86 and 87-99. To further define the principles of nasal tolerance induction, we generated three different MBP peptides (MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and evaluated whether their nasal administration on day -11, -10, -9, -8 and -7 prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection to Lewis rat EAE. Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage compared to that being used for individual peptides. Rats tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA expressing cells were observed in the two groups. Nasal administration of MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord homogenate-induced EAE, and passive transfer of spleen mononuclear cells from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE. Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse ongoing EAE induced with gp-MBP, although higher doses are required compared to the dosage needed for prevention. In conclusion, nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.