Effect of leptin on the regulation of placental hormone secretion in cultured human placental cells.

Placenta is an important source of leptin during pregnancy that contributes to the high plasma leptin levels in pregnant women. Leptin and its functional receptors are synthesized in trophoblast cells that, in turn, secrete gestational hormones supporting a paracrine or autocrine role for leptin in the endocrine activity of the placenta. In the present study we examined the effect of leptin on in vitro release of gestational hormones (human chorionic gonadotropin (hCG), human placental lactogen (hPL), progesterone, estrogens and testosterone) by human term placental cells in culture. Placentas at term were obtained immediately after delivery from mothers with uncomplicated pregnancies. Progesterone, hCG, hPL, estradiol, estrone, estriol and testosterone levels were measured by different assays in culture media of cells maintained in monolayer culture after incubation for 12, 24, 48 or 72 h with leptin or placebo. Incubation with leptin did not modify hCG, hPL, progesterone, estriol and estrone secretion for any of the doses and times assayed. However, leptin led to a dose-dependent decrease in estradiol release. This effect was observed when treatment with recombinant human leptin spanned from 12 to 72 h. At this time an increase in testosterone levels was observed in leptin-treated cells versus placebo. These results indicate that leptin can be considered a gestational hormone implied in the endocrine function of the placenta, with an important role in control of the production of steroid reproductive hormones in placental cells in vitro.     

Determinants of left ventricular systolic function recovery after an acute coronary syndrome.

INTRODUCTION: Ischemic heart disease is a major cause of heart failure in western societies. However, the factors that may influence left ventricular function (LVF) recovery after an acute coronary syndrome (ACS) are still unclear. OBJECTIVE: To identify variables that may influence LVF evolution one year after ACS. METHODS: 104 patients hospitalized with ACS between 7/1/2001 and 12/31/2002 and with systolic dysfunction--defined as an echocardiographic ejection fraction (EF) < or = 45%--were randomly allocated to a planned coronary follow-up program (FUP) or a general cardiology clinic (GC); patients from both groups were also randomly referred to a structured cardiac rehabilitation program (CRP). EF was re-assessed at one year. We compared differences between patients who recovered left ventricular function (EF > 45%; group 1) and those who did not (group 2). RESULTS: One year after discharge, 44.2% of the patients had recovered function. There were no significant differences between the groups in gender (77.7 vs. 76.5% male), age (56 vs. 59 years), hypertension, diabetes, dyslipidemia, smoking habits or family history. A previous history of cardiovascular events was more frequent in group 2 (11.1% vs. 35.3%, p = 0.03). Cardiac catheterization was performed before discharge in 88.8% and 88.2% in groups 1 and 2 respectively (p = NS); no differences were found in coronary anatomy between the two groups. Angioplasty was performed in 54.2% in group 1 and 50% in group 2 (p = NS). There were no differences in the use of angiotensin-converting enzyme inhibitors (83.3% vs. 87.5%), beta-blockers (87.5% vs. 87.5%), nitrates (37.5% vs. 33.3%), aspirin (95.8% vs. 95.8%), statins (79.1% vs. 75%) or diuretics (20.8% vs. 45.8%). There was no significant difference in LVF recovery between patients randomized to FUP or GC (38.5% vs. 54.5%). 87.5% of patients who completed the CRP had normal EF at one year compared to 32.7% of patients not referred to the program (p = 0.009). Although EF improved in both groups, this improvement was greater in patients who completed a CRP (EF 8% vs. 5%, p = 0.003). CONCLUSION: A previous cardiovascular event and completion of a CRP were the only variables that influenced LVF recovery. Thus, enrollment in a CRP, in addition to standard therapy, could be an important therapeutic measure in patients with systolic dysfunction after ACS; our data suggest that these programs should be more widely used.     

ImmunoCyt/uCyt+ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma.

ImmunoCyt/uCyt is a fluorescent test combining three monoclonal antibodies. In this study, it has been tested as a complement to cytology in the detection of urothelial carcinoma in urine. It has been performed simultaneously with standard cytology and cystoscopy on 870 urine analyses from one hospital. In 136 cases, one or more bladder tumors were found. Overall sensitivity of cytology, ImmunoCyt/uCyt and combined analyses reached 29, 74 and 84%, respectively, and overall specificity was 98, 62 and 61%. The negative predictive value of cytology, ImmunoCyt/uCyt and both analyses was 88, 93 and 95%, respectively, and the positive predictive value was 70, 26 and 29%. The sensitivity of cytology for low malignant potential neoplasms, low- and high-grade papillary carcinomas was 6, 18 and 53%, while it reached 71, 79 and 93% when combined with ImmunoCyt/uCyt. The sensitivity of cytology for stages Ta, T1, T2 and over and Tis tumors was 12, 67, 47 and 50%, while it reached 78, 83, 79 and 100% when combined with ImmunoCyt/uCyt. In the absence of tumor on cystoscopy but with positive ImmunoCyt/uCyt, 18% of patients developed a tumor, 2-6 months later. Of the 109 cases diagnosed as suspicious for malignancy by cytology, a tumor was present in 30 cases and ImmunoCyt/uCyt was positive in 22 (73%) of them. In conclusion, ImmunoCyt/uCyt may be used to postpone cystoscopies in patients followed for bladder cancer and may help to save cytologist and pathologist screening time.     

Study of the localization of radiopacities similar to calcified carotid atheroma by means of panoramic radiography.

OBJECTIVE: To determine the location in soft tissues of the calcifications, similar to calcified carotid atheromas, that can be observed radiographically in the cervical region in panoramic radiographs. STUDY DESIGN: In each anatomic cadaver specimen preserved in formol, consisting of the head and neck, radiopaque spheres (made from gutta-percha) were positioned in anatomic structures of the cervical region that can be sites of calcification. For each anatomic structure marked in this way, panoramic radiography was performed, consisting of 17 radiographs. The images obtained were analyzed by 24 examiners who indicated which radiographs, in their opinion, presented the radiopaque reference projected in the region of bifurcation of the carotid artery. Analysis of 2 proportions from agreement and disagreement was used to determine radiopacities that could be confused in panoramic radiographs with calcified atheromas in the carotid artery. RESULTS: The results showed that 75% (18) of the examiners correctly indicated the reference in the bifurcation of the carotid artery and 79.2% (19) indicated a triticeous cartilage as calcified atheroma of the carotid artery. CONCLUSIONS: Calcified atheromas of the carotid artery are not the only features that can produce radiopaque images lateral to the panoramic radiograph; the presence of calcification in the triticeous cartilage also can induce an erroneous diagnosis of calcified carotid atheroma.     

Cementoblastoma related to a primary tooth: a case report

Cementoblastomas are benign lesions of the odontogenic ectomesenchyme that rarely occur related to the primary dentition, especially on the left side of the mandible. This study describes a case of a true cementoblastoma related to the left second primary mandibular molar in a 7-year-old child (the largest one seen in the left side of the mandible). Additionally, the radiographic and histologic findings of the lesion are described in details.     

Corneal allograft rejection in rabbits

We performed a phase I study to assess the therapeutic efficacy of an anti-T cell monoclonal antibody conjugated with ricin A-chain in a corneal graft rejection model. Corneal allografts were exchanged between Dutch and New Zealand rabbits. Rejections occurred within 16-22 days in untreated animals. Graft rejection was delayed by topical or retrobulbar cyclosporine, but not by subconjunctival injections of a murine anti-rabbit T cell monoclonal antibody, nor by either subconjunctival or intravenous F(ab')2-ricin conjugate.     

Genetic polymorphisms and risk of recurrent deep venous thrombosis in young people: prospective cohort study.

OBJECTIVE: To determine the incidence of deep venous thrombosis (DVT) recurrence in young people, and its association with some genetic polymorphisms (FV G1691A, FII G20210A, MTHFR C677T, PAI-1 4G/5G). DESIGN: Prospective cohort study. METHODS: A database was established prospectively to follow-up a cohort of unselected patients who had had a first episode of objectively proven DVT under the age of 40 years. All patients had DNA analysis for heritable thrombophilia. We excluded patients with deficiency of antithrombin, protein C or protein S, malignant disease, antiphospholipid syndrome, or a requirement for long-term antithrombotic treatment. The end-point was objective evidence of symptomatic DVT recurrence. RESULTS: Eighty-seven patients were enrolled in the study. Mean duration of follow-up was 4.07 years. At 2 years, the cumulative recurrence rate was 19.3%. The risk of risk was not related to presence or absence of laboratory evidence of genetic polymorphisms: FV G1619A (HR 1.26 [95%CI: 0.64-2.46]; p = 0.51), FII G20210A (HR 0.81 [95%CI: 0.35-1.89]; p = 0.62), MTHFR C677T (HR 1.26 [95%CI: 0.56-2.81]; p = 0.58), PAI-1 4G/5G (0.84 [95%CI: 0.35-2.05]; p = 0.71). CONCLUSION: In this study, the risk of recurrent deep venous thrombosis in young people was not related with the presence of FV G1691A, FII G20210A, MTHFR C677T or PAI-1 4G/5G polymorphisms.     

Medullar expression of type-A natriuretic peptide receptor in an animal model of hypertension induced by renal mass ablation.

INTRODUCTION: The biological activity of the natriuretic peptide (NP) system is dependent on the balance between NP tissue levels and the local expression of their receptors. In the kidney, the natriuretic peptide receptor type A (NPR-A) is the principal receptor mediating NP activity and is mainly expressed in the renal medulla. An increase in circulating NP levels is well documented in chronic renal failure (CRF); however, the renal expression of NPR-A has not been evaluated in this condition. METHODS: Wistar-Han rats were submitted to right nephrectomy plus ablation of both poles of the left kidney (3/4nx; n=27) or were sham operated (Sham; n=22) and followed for up to 26 weeks post surgery. Blood pressure measurements were performed weekly. Two, 10 and 26 weeks after surgery, renal sodium and creatinine excretion were evaluated and the kidneys removed for NPR-A mRNA quantification by real-time PCR. The results of mRNA quantification are expressed in arbitrary units (AU) set as the mean value of the Sham group (Sham=1 AU), after normalization for GAPDH (p<0.05). weeks after surgery) and in elevated fractional sodium excretion (+270%, 26 weeks after surgery). Although sodium intake was similar in 3/4nx and Sham rats, blood pressure was higher in 3/4nx rats and increased progressively throughout the study. This was accompanied by a marked decrease in NPR-A mRNA levels in the renal medulla from 3/4nx animals at 2, 10 and 26 weeks post surgery. Conclusion: In 3/4nx rats, the expression of NPR-A in the renal medulla of the remnant kidney is markedly reduced from 2 weeks up to 26 weeks post surgery. It is suggested that this may contribute to the progressive increase in blood pressure, as well as to the renal fibrosis observed in 3/4nx rats.     

Cardiovascular protection from alcoholic drinks: scientific basis of the French Paradox.

This article discusses the cardiovascular protection afforded by low to moderate consumption of ethanol and the role of ethanol-induced preconditioning. Ethanol, a compound that is found in many popular beverages, has a whole range of cardiovascular protective effects when consumed in low to moderate doses. Although they have yet to be totally clarified, recent data suggest that a combination of several actions at the biochemical and molecular levels play a role in this protection. These include favorable changes in lipid metabolism, antioxidant effects, changes in hemostasis and platelet aggregation, arterial vasodilation mediated by NO release, induction of the expression of cardioprotective proteins, insulin sensitization and lower levels of inflammatory markers. Special emphasis will be given to ethanol-induced preconditioning. Some of the compounds present in red and white wine, such as resveratrol and quercetin, are also partly responsible for some of the cardioprotective effects of alcoholic drinks. These are due to antioxidant effects and changes in platelet aggregation, endothelial function and inflammatory response. The last part of the paper will focus on the clinical applications and possibilities raised by these new findings.     

To die with dignity.

This paper examines the conundrum facing an individual with a terminal disease who wishes to end his or her life in a manner that maintains a minimum of dignity. The State's interest versus the individual's right to live or die is examined in its various aspects. The interference by the State supplanting the Church as the authority that interprets the boundaries between life and death, with the individual losing his voice as well as his body to the impersonality of maintaining a life not worth living, is studied, as well as the implicit dangers when the freedom to decide when and who should die is measured against the present international economic situation. The need to listen to the language of the dying as well as to their need for a 'closure' is approached with a view to future study.