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Biomedical subjects

D Pace

Publications and source records attributed to D Pace.

18 recordsLinked to original sources
PubMed2005

Sphingosine releases Ca2+ from intracellular stores via the ryanodine receptor in sea urchin egg homogenates.

Various reports have demonstrated that the sphingolipids sphingosine and sphingosine-1-phosphate are able to induce Ca2+ release from intracellular stores in a similar way to second messengers. Here, we have used the sea urchin egg homogenate, a model system for the study of intracellular Ca2+ release mechanisms, to investigate the effect of these sphingolipids. While ceramide and sphingosine-1-phosphate did not display the ability to release Ca2+, sphingosine stimulated transient Ca2+ release from thapsigargin-sensitive intracellular stores. This release was inhibited by ryanodine receptor blockers (high concentrations of ryanodine, Mg2+, and procaine) but not by pre-treatment of homogenates with cADPR, 8-bromo-cADPR or blockers of other intracellular Ca2+ channels. However, sphingosine rendered the ryanodine receptor refractory to cADPR. We propose that, in the sea urchin egg, sphingosine is able to activate the ryanodine receptor via a mechanism distinct from that used by cADPR.

Animals↗
PubMed2001

Transperitoneal laparoscopic nephrectomy for giant polycystic kidneys: a case control study.

OBJECTIVES: To describe the technique and compare the surgical outcomes of patients with autosomal dominant polycystic kidney disease (ADPKD) undergoing laparoscopic or open nephrectomy for giant kidneys. METHODS: The surgical outcome of our first 10 consecutive patients with ADPKD who underwent laparoscopic nephrectomy was analyzed from a large prospective computer database. The results were compared with the 10 most recent open nephrectomy procedures performed for ADPKD at the same institution. To facilitate safe laparoscopic hilar dissection, the kidneys were made manageable by volume reduction, accomplished through diligent cyst puncture and aspiration using a novel prototype suction device with a beveled tip. RESULTS: No statistically significant differences were found between the laparoscopic and open surgical groups relative to patient sex, age, or median preoperative kidney size (24.0 versus 21.5 cm, respectively). The laparoscopic patients were significantly heavier than their open counterparts (94 versus 78 kg, P = 0.0095) and had a longer operative time (247 versus 205 minutes, P = 0.04). One conversion to open surgery occurred in the laparoscopic group because cysts were adherent to the spleen and colonic mesentery. No intraoperative complications or deaths occurred in either group and the postoperative complications were similar. The mean length of the postoperative hospitalization was markedly reduced with the laparoscopic compared with the open approach (2.6 versus 6.6 days, P = 0.00002). At a median of 12 months after surgery, none of the laparoscopic patients had recurrent pain, bleeding, or infection. CONCLUSIONS: Laparoscopic nephrectomy is technically safe and feasible in patients with ADPKD. Progressive cyst aspiration is a critical step, facilitating the identification of vital structures and the creation of enough abdominal cavity space to operate. The advantages of this minimally invasive technique include a short hospital stay, minimal pain, low morbidity, and superior cosmesis.

Adult↗
PubMed2000

Orlistat fails to alter postprandial plasma lipid excursions or plasma lipases in normal-weight male volunteers.

OBJECTIVES: After 10 d of orlistat administration (120 mg three times/day), the primary objective was to determine the drug's effect on postprandial plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities on day 10 after an oral fat-load. The secondary objectives were to determine the effects of orlistat on 12 h postprandial measures of: (1) preheparin HTGL and LPL; and (2) serum triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and free fatty acids. METHODS: Twenty-four normal-weight, healthy male volunteers were randomized to either 120 mg orlistat (n=12) or placebo (n=12) three times a day with meals for 10 d. Preheparin LPL and HTGL activities and LPL specific activity were measured in the fasted state on days 1, 5, and 10. On days 5 and 10 the study medication (orlistat or placebo) was taken at the beginning of a fat-rich breakfast and serum lipid and lipoprotein levels monitored for 12 h postprandially. On day 10, 15 min postheparin HTGL activity was measured 8 h after the fat-rich breakfast. RESULTS: No differences were found between groups in fasting levels of preheparin LPL or HTGL activity or in LPL-specific activity on days 1, 5 and 10. No difference was found between the two treatment groups in postheparin HTGL activity 8 h after the fat-rich breakfast. Also, no differences were found between the two groups in plasma triglycerides or lipoproteins. CONCLUSION: The results indicate that the oral administration of orlistat (120 mg t. i.d.) does not significantly alter plasma triglycerides or lipoproteins, and that the inhibitory effect of orlistat on lipases is limited to the gastrointestinal tract and is not manifested systemically.

Adult↗
PubMed1999

Delay in diagnosis of breast cancer.

OBJECTIVES: To assess the consequences of physician delay in the diagnosis of breast cancer by comparing stage, treatment, and outcome of patients with and without delay, and to identify patient characteristics that may make diagnosis more difficult. SUMMARY BACKGROUND INFORMATION: Delay in diagnosis of breast cancer is the most common clinical scenario resulting in malpractice litigation. METHODS: The records of 1014 patients were reviewed and the events preceding the diagnosis were reconstructed. Accurate assessment of the physician delay in diagnosis could be made for 606 patients, 51 (8%) with physician delay >3 months. Patients with delay were comparable to patients without delay in terms of age, height, weight, age at menarche, pregnancies, children, proportion in menopause, age at menopause, and family history of breast cancer. RESULTS: Thirty-six percent of patients who had a delay in diagnosis had normal mammograms versus 7% of patients without delay. Cancers in patients with delay were significantly larger on average than in those without delay, but there were no significant differences in pathology, differentiation, nodal status, TNM stage, treatment, or outcome. CONCLUSIONS: Physician delay in the diagnosis of breast cancer is common, and patients with delay are similar to patients without delay, although they are more likely to have normal mammograms. The consequences of physician delay in terms of stage at diagnosis, treatment, and outcome were not statistically significant.

Adult↗
PubMed1997

Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast.

OBJECTIVES: The degree and duration of protection against exercise-induced bronchoconstriction afforded by three doses of a specific leukotriene D4 receptor antagonist, cinalukast, were assessed after an initial dosing and after 1 week of therapy. METHODS: A placebo-controlled crossover study was performed in eight male patients who had mild, stable asthma and exercise-induced bronchoconstriction. Treatment consisted of four 7-day periods of placebo and three dose levels of the drug (10, 50, and 200 mg administered orally). Exercise challenge was performed at 2 hours and 8 hours after treatment on the first and seventh treatment days. The response was measured as the area under the FEV1-time effect curve (AUEC). RESULTS: On the first day of treatment, the mean (+/- SEM) AUEC at 2 hours was 24.2 +/- 3.3 L.min after placebo and was 5.5 +/- 2.2 L.min, 6.3 +/- 2.7 L.min, 3.3 +/- 3.8 L.min after 10 mg, 50 mg, and 200 mg, respectively (p < 0.05 for all values compared with placebo). The AUEC at 8 hours on the first day was 25.1 +/- 4.4 L.min after placebo and was 6.8 +/- 4.1 L.min, 11.2 +/- 2.5 L.min, and 5.0 +/- 2.8 L.min after 10 mg, 50 mg, and 200 mg, respectively (p < 0.05 for all values compared with placebo). The protection afforded by 10 mg of cinaluicast was lost after 7 days of treatment but persisted with 50 mg and 200 mg doses. CONCLUSION: Orally administered cinalukast provides at least 8 hours of protection against exercise-induced bronchoconstriction. This protection is lost with regular treatment for 1 week for the lowest dose studied.

Administration, Oral↗
PubMed1993

Effectiveness of thymostimulin and study of lymphocyte-dependent antibacterial activity in children with recurrent respiratory infections.

Recurrent respiratory infections (RRI) consist of more relapsing acute respiratory infections than the ones expected for the age [> 6 acute respiratory tract infections (RTI) per year if age is > 3 years, and > 8 acute RTI per year if age is < 3 years]. Concerning the pathogenesis of RRI, several investigations report the important role of environmental factors, early socialization and immunological dysfunctions, such as lymphocyte subpopulations alterations, IgG subclass deficiency and phagocytosis and/or opsonization deficit during acute infections. In this framework, we have studied the lymphocyte-dependent antibacterial activity (ABA) among 121 children affected by RRI. Results show a statistically significant alteration of this function in 38 children (31.4%): 19 of them exhibited an absent ABA (group 1), while in the others same function was reduced (group 2). A bovine thymic extract, thymostimulin, was administered to both groups by intramuscular injections (1 mg/kg) for a 3 month cycle. At the end of therapy we observed a statistical significant rise of ABA only in group 1 and among children aged > 3 years. Among the same patients, 33 children (86.8%) improved in terms of reduction of clinical score and better results were seen among children aged > 3 years. These data emphasize the beneficial role of thymostimulin in RRI-affected children, suggesting a transient immaturity of the immune system as one of the possible pathogenetic factor.

Adjuvants, Immunologic↗
PubMed1991

Granulated lymphocytes in human endometrium: histochemical and immunohistochemical studies.

Granulated lymphocytes with an unusual antigenic phenotype (CD56+ CD38+ CD2 +/- CD3- CD16-) form a substantial proportion of leukocytes in human endometrial stroma. The purpose of this study was to examine morphological and antigenic heterogeneity in endometrial granulated lymphocytes (eGL) in imprint preparations, paraffin-embedded sections and frozen sections. eGL in decidual imprints showed variations in cell size, nuclear size, shape and chromatin content and the number and size of cytoplasmic granules. eGL were detected in paraffin-embedded sections using phloxine tartrazine, alcian blue and toluidine blue stains. There was no difference in the number of eGL among the three stains but the granules appeared smaller and more regular when stained with toluidine blue. The proportion of stromal cells which were leukocytes increased from 8.2% in proliferative endometrium to 31.7% in early pregnancy decidua. The number of CD56+ and CD38+ cells increased in late secretory endometrium; CD56+ cells formed greater than 75% of the leukocytes in first trimester decidua. The increased number of CD2+ cells in decidua was not comparable with CD56+ and CD38+ cells suggesting that a lower proportion of CD56+ cells in first trimester decidua coexpress CD2, an observation which was supported by double labelling studies. eGL therefore show morphological and antigenic heterogeneity and the study of granulated lymphocytes in pathological endometrium and decidua will require careful phenotypic and morphological analysis of accurately dated samples.

Antibodies, Monoclonal↗
PubMed1991

Characterization of intraepithelial lymphocytes in human endometrium.

Intraepithelial lymphocytes (IELs) were characterized and quantitated in normal non-pregnant endometrium and in early pregnancy decidua using H & E and phloxine tartrazine stains and a panel of monoclonal antibodies in an indirect immunoperoxidase technique. The relative numbers of granulated and non-granulated IELs varied according to menstrual cycle stage and in early pregnancy all IELs appeared to be granulated. There was a higher surface:gland ratio for IELs in proliferative endometrium compared with late secretory phase and early pregnancy endometrium. In proliferative endometrium most IELs were T cells, predominantly of the CD8 + subset. In first trimester decidua, higher numbers of CD56 + cells were observed, in keeping with the increased proportion of granulated IELs. IEL populations in human endometrium vary according to menstrual cycle stage and endometrial IELs appear to show phenotypic differences compared with IELs in the human gastrointestinal tract.

Antibodies, Monoclonal↗
PubMed1989

Proliferative activity in endometrial stromal granulocytes throughout menstrual cycle and early pregnancy.

The proliferative activity in endometrial stromal granulocytes was studied using two approaches. Firstly, mitotic activity was studied in paraffin wax embedded sections of normal non-pregnant endometrium and early pregnancy decidua stained with phloxine-tartrazine. Secondly, the monoclonal antibody Ki67 was applied to cryostat sections of similar tissues. Endometrial stromal granulocytes were identified by their labelling with NKH1, Dako T11, UCHL1 or Dako-LC. The percentage of cases in which endometrial stromal granulocytes showed mitosis was 25%, 75%, 86%, and 93%, respectively in proliferative, early secretory, mid secretory, and late secretory phases, and 14% in early decidua. There were at most one or two endometrial stromal granulocytes in mitosis per 10 high power fields. Double labelled cells were present in small numbers in proliferative endometrium and in moderate numbers in secretory endometrium. Only a few cells in early decidua double labelled with Ki67/T11; moderate numbers of cells double labelled with Ki67/Dako-LC. It is concluded that proliferative activity does occur in endometrial stromal granulocytes and is particularly prominent in the late secretory phase.

Decidua↗
PubMed1988

Immunoregulatory cells in human decidua: morphology, immunohistochemistry and function.

Suggestions that local intrauterine materno-fetal immune interactions may be important for normal pregnancy have led to investigation of immunoregulatory function by decidualised endometrium. Human decidua is complex and cell types may be difficult to distinguish at the light microscope level. Immunohistochemical techniques have allowed antigenic identification of cells within decidua and abundant leucocytes are present throughout pregnancy. Macrophages (CD14+) are abundant in decidua basalis and decidua parietalis throughout pregnancy and may be closely associated with extravillous trophoblast. Expression of class II MHC antigens and CD11c may suggest an immunological role but their content of lysosomal enzymes could indicate phagocytic functions. Antigen-presenting capacity has been noted in early human decidua and may be due to macrophages. Decidual macrophages have also been attributed with immunosuppressive function due to secretion of prostaglandin E2. Decidual granulated lymphocytes are abundant in the first trimester and correspond to the so-called endometrial stromal granulocytes. They express CD2, CD7, CD38 and NKH1 but are negative for classical T cell and NK cell markers and they do not express the IL2 receptor. Semipurified populations show low levels of cytotoxicity in a standard NK assay. Thus, immunohistochemical techniques have allowed characterisation of potentially immunocompetent cells in human decidua. However, their roles both in vitro and in vivo remain to be established with certainty.

Antigens, Surface↗
PubMed1986

Failure of superoxide dismutase and catalase to alter size of infarction in conscious dogs after 3 hours of occlusion followed by reperfusion.

Superoxide dismutase (SOD) and catalase (CAT), enzymes that degrade superoxide anion and hydrogen peroxide, respectively, reduce size of infarction in anesthetized, open-chest dogs subjected to coronary occlusion followed by reperfusion. To evaluate potential protective effects of these enzymes in conscious animals, three groups of dogs were instrumented at sterile surgery with a hydraulic occluder on the left circumflex (LCX) coronary artery, sonomicrometers to measure regional wall thickness, and catheters to monitor arterial and left ventricular pressures. Ten to 14 days after surgery, the animals were sedated with morphine sulfate (0.5 mg/kg). The LCX artery was occluded for 3 hr by inflation of the hydraulic cuff. Infusions of SOD (n = 7), CAT (n = 6), or saline (control group, n = 7) were begun 15 min before reperfusion and lasted for 45 min of reperfusion. The doses of SOD and CAT were 5 mg/kg, dissolved in 60 ml of saline, and infused at a rate of 1 ml/min. Myocardial blood flow was measured with tracer-labeled microspheres (15 micron diameter) before occlusion, after 5 to 10 min of occlusion, after 150 min of occlusion, and 5 to 10 min after reperfusion. Size of infarction was measured 24 hr later by dual-perfusion staining with Evans blue and triphenyl tetrazolium. Size of infarction (expressed as a percentage of area at risk) did not differ significantly among the three groups: control, 32 +/- 17% (mean +/- SD); SOD, 38 +/- 17%; CAT, 27 +/- 17%. Hemodynamic parameters and myocardial blood flows (measured before infusion of any agents) were not significantly different among the three groups. Serum SOD levels in SOD-treated dogs were 19 +/- 2 micrograms/ml at the onset of reperfusion and 29 +/- 3 micrograms/ml at the end of the infusion. Blood assays collected after infusion showed a monoexponential decay of SOD levels with a half-life of 22 +/- 6 min. We conclude that myocardial protection by SOD or CAT is model dependent. In conscious dogs subjected to 3 hr of coronary occlusion followed by reperfusion, SOD and CAT failed to alter size of infarction.

Animals↗
PubMed1983

Biotransformation of cibenzoline to 2-(2,2-diphenylcyclopropyl)-1H-imidazole.

A microsomal metabolite of cibenzoline, 4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole butanedioate, was identified by n.m.r. as the 4,5-dehydro analogue, 2-(2,2-diphenylcyclopropyl)-1H-imidazole. Three dogs dosed orally with 13.8 mg/kg 14C-cibenzoline base excreted 1.8-3.5% of the dose as this metabolite in the urine. Mean plasma concentrations of cibenzoline reached a peak of 1.5 micrograms/ml at 2 h while mean concentrations of the metabolite of 0.4-0.5 micrograms/ml were found between 2 and 7 h. The metabolite was synthesized and found to decrease the frequency of ventricular premature depolarizations in conscious dogs having a two-stage occlusion of the left anterior descending coronary artery performed 48 h before. It did not inhibit ventricular arrhythmia in rats induced by i.v. infusion of aconitine. Thus, in contrast to cibenzoline, the metabolite does not appear to be a true antiarrhythmic agent.

Animals↗
PubMedDate not supplied

[Genetic, polyphysiographic, CT and therapeutic aspects (author's transl)].

Genetic, clinical, polyphysiographic and therapeutical aspects were investigated in a 37 year old patient suffering from: sporadic and localized segmentary myoclonia (present during rest and increasing slightly during movement), cerebellar syndrome, marked hypoacusia, hyper-reflexia of the lower limbs, spike and polyspike EEG discharges and massive myoclonia during photostimulation. A dominant autosomic inheritance of this syndrome was suggested by the occurrence of a more serious and rapid, yet similar, illness in the mother and by EEG alterations in an 8 year old son. The Authors suggest that, from the clinical point of view, they are dealing with an atypical Ramsay-Hunt syndrome (MCD) with signs of Pierre-Marie Heredoataxia. This supports the possibility, however rare, of intermediate forms between MCD and Heredoataxia. The patient underwent polyphysiographic investigations under the following conditions: i) without therapy; ii) with diphenylhydantoin; iii) with phenobarbital; iv) with sodium dipropyl-acetate; v) with clonazepam. The above investigations confirmed the previously described alterations, during wakefulness or sleep, observed in cases of Unverricht-Lundborg syndrome (PME) and Ramsay-Hunt syndrome (MCD). Clonazepam was found to be the most effective drug in attenuating myoclonia, in reducing the EEG spike activity and in reorganizing the phases and cycles of sleep.

Adult↗