Obstetric and gynecologic complications in women with Marfan syndrome

OBJECTIVE: To analyze the maternal and fetal outcomes of pregnancy and gynecologic problems in women with Marfan syndrome. STUDY DESIGN: The outcomes of 14 pregnancies in 4 women with Marfan syndrome were prospectively observed between January 1988 and December 2000. The cardiovascular and obstetric complications were analyzed. During pregnancy all the patients were carefully monitored with serial echocardiography and close attention to symptoms. RESULTS: Of the 14 pregnancies, 5 (35.7%) ended in abortion, and 3 of them occurred in the early second trimester due to cervical incompetence. Premature onset of labor occurred in 2 pregnancies at 31 and 34 weeks. Postpartum hemorrhage complicated 3 deliveries, and inversion of the uterus occurred in 1 patient. Significant cardiovascular complications occurred in 2 patients, who required surgical correction of the aortic aneurysm and replacement of the aortic valve. In one patient the operation was performed within hours of vaginal delivery, and the other patient underwent surgery 8 weeks postpartum. No maternal death occurred in the study. One infant in the series was diagnosed as having Marfan syndrome. A premature infant delivered at 31 weeks died on the second day of life. CONCLUSION: Women with Marfan syndrome are at high risk of aortic dissection in pregnancy even in the absence of preconceptional aortic root dilatation. Obstetric complications in patients with this condition have been underreported in the past. Women with aortic root dilatation of < 40 mm usually tolerate pregnancy well, with good maternal and fetal outcomes. Women with Marfan syndrome should be counseled regarding the risk of pregnancy to both mother and fetus. Patients who have cardiac decompensation or aortic dilatation > 40 mm are advised to avoid pregnancy.     

Plasmacytic hyperplasia--the early form of posttransplant lymphoproliferative disorder--with atypical morphology and clinical course in patient after liver transplantation: a case report

This case report describes an early lesion of posttransplant lymphoproliferative disorder (PLTD)--plasmacytic hyperplasia with atypical morphology. The 54-year-old patient was 4 months after liver transplantation due to alcoholic cirrhosis. The postoperative course had been uneventful without graft rejection episodes. Primary immunosuppressive therapy included tacrolimus and prednisone. On admission to the hospital the patient showed rapidly increasing jaundice, hepatomegaly, anemia, thrombocytopenia, and significant leukocytosis. A biopsy suggested generalized infection. Acute Epstein-Barr virus (EBV) infection was confirmed using serological methods. Despite treatment the patient died. On autopsy we found features of generalized infection. Histological examination of the enlarged lymph nodes showed plasmacytic hyperplasia despite lymph node atrophy. Plasmacytic hyperplasia, an early lesion of PTLD despite usually a good prognosis with multifactor therapy may display a rapid course that leads to death through intensified immunosuppression. In accordance with other reports we confirmed reactivation of EBV infection as the probable cause of plasmacytic hyperplasia. The lymph node morphology of plasmacytic hyperplasia may be atypical with atrophy of lymphoid components accompanying plasma cell proliferation.     

Petroleum hydrocarbon toxicity in vitro: effect of n-alkanes,benzene and toluene on pulmonary alveolar macrophages and lysosomal enzymes of the lung

The in vitro effects of straight chain alkanes (nC₆-nC₁₀), benzene and toluene on pulmonary alveolar macrophages (PAM) of rats and rabbits was studied. The concentrations used ranged from 0.02 to 1.0 mM. All hydrocarbons used in the study were cytotoxic to isolated cultured PAM cells in a dose-dependent manner. The LC₅₀ for these hydrocarbons towards rat PAM cells was estimated to be 1.0 mM for nC₈, 2 mM for nC₇, 5 mM for nC₉ and 10 mM for nC₆, nC₁₀, benzene and toluene. Rabbit PAM cells were more sensitive to the hydrocarbons, resulting in an LC₅₀ half that for rat PAM cells. Hydrocarbons also caused extracellular release of the lysosomal enzymes cathepsin D (EC 3.4.23.5) and cathepsin B (EC 3.4.22.1) in a manner corresponding with cell damage. There was more cathepsin D activity released from cells than cathepsin B. In addition, hydrocarbons also caused the release of cathepsin B and D from isolated lysosomes, and there was 10–15% more enzyme activity released in the culture medium of lysosomes exposed to concentrations of 0.5 and 1.0 mM compared to PAM cell cultures of either rats or rabbits. Hydrocarbons also caused loss of cell respiration and stimulated a dose-dependent and a time-dependent increase in lipid peroxidation. The two alkanes nC₇ and nC₈ caused the greatest increase in lipid peroxidation and the greatest loss of cell respiration. The results indicate that there is a relationship between chain length of alkanes and their cytotoxicity to PAM cells. The results also demonstrate a good correlation between decreased cell viability, increased lysosomal enzyme release, decreased cell respiration and increased lipid peroxidation in response to the hydrocarbons.     

Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics

Open-heart surgery triggers an inflammatory response that is largely the result of surgical trauma, cardiopulmonary bypass, and organ reperfusion injury (e.g. heart). The heart sustains injury triggered by ischaemia and reperfusion and also as a result of the effects of systemic inflammatory mediators. In addition, the heart itself is a source of inflammatory mediators and reactive oxygen species that are likely to contribute to the impairment of cardiac pump function. Formulating strategies to protect the heart during open heart surgery by attenuating reperfusion injury and systemic inflammatory response is essential to reduce morbidity. Although many anaesthetic drugs have cardioprotective actions, the diversity of the proposed mechanisms for protection (e.g. attenuating Ca(2+) overload, anti-inflammatory and antioxidant effects, pre- and post-conditioning-like protection) may have contributed to the slow adoption of anaesthetics as cardioprotective agents during open heart surgery. Clinical trials have suggested at least some cardioprotective effects of volatile anaesthetics. Whether these benefits are relevant in terms of morbidity and mortality is unclear and needs further investigation. This review describes the main mediators of myocardial injury during open heart surgery, explores available evidence of anaesthetics induced cardioprotection and addresses the efforts made to translate bench work into clinical practice.     

A new cembrane-type diterpenoid from Bornean liverwort Chandonanthus hirtellus

A new compound, chandonanol (1), along with four known compounds, chandonanthone (2), iso-chandonanthone (3), anastreptene (4), and (6R,7S)-sesquiphellandrene (5), was isolated from the MeOH extract of Bornean liverwort Chandonanthus hirtellus. The structure of the new metabolite was established by analyses of the spectroscopic data (1D NMR, 2D NMR, HRESIMS, and IR). These compounds were tested for their activity against antibiotic-resistant clinical strains. Chandonanol (1) exhibited potent bactericidal activity against Staphylococcus aureus and Escherichia coli.     

Outcome assessment of the Ministry of Health Malaysia dialysis programme

We describe the outcomes on haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) provided by the Ministry of Health (MOH). The assessment was based on data from the Malaysian Dialysis Registry on 2480 HD and 732 CAPD patients who commenced dialysis between 1980 and 1996. Young patients (age < 40) have remarkable long term survival (life expectancies of 16 years on HD, 18 years on CAPD). Adjusting for background mortality, relative survival of older patients was as good as younger ones. Diabetics did poorly. 52% of HD and 26% of CAPD patients were employed in 1996. 71% of HD patients scored 10(normal) on QL index (a measure of quality of life) while 60% of CAPD patients have similar score. Differences in rehabilitation and QL index scores by age, gender and diabetes were also observed. Outcomes of dialysis in the MOH programme are reassuring.     

Phase I/II trial of (131)I-MN-14F(ab)2 anti-carcinoembryonic antigen monoclonal antibody in the treatment of patients with metastatic medullary thyroid carcinoma

BACKGROUND: Monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA) have been recognized as targeting agents for medullary thyroid carcinoma (MTC). This Phase I/II study was initiated to determine the safety, maximum tolerated dose (MTD), and therapeutic potential of (131)I-MN-14 F(ab)2 anti-CEA MAb for patients with metastatic MTC. METHODS: Fifteen patients were enrolled in this study. Dose escalation was based on estimates of radiation dose to the bone marrow, and the radioactive dose given was determined by a pretherapy diagnostic study in which 8 mCi (0.6-20 mg) of (131)I-MN-14 F(ab)2 was administered 1 week prior to therapy. RESULTS: Three patients received an initial dose of 140 centigray (cGy) to bone marrow, 11 received 180 cGy, and 1 received 220 cGy. Myelosuppression was the only significant treatment-related dose-limiting toxicity (DLT), and the MTD appeared to be 180 cGy to the bone marrow. Human antimouse antibodies (HAMA) developed in 8 patients 2-6 weeks after therapy. Seven patients had a median of 55% reduction of tumor markers. One patient showed a dramatic improvement in the mass effect on the airways caused by 3 tumor lesions in the neck, with a 45% reduction of overall tumor burden. The disease has continued to be radiologically stable in 11 of 12 assessable patients for periods ranging from 3+ to 26+ months. CONCLUSIONS: Therapy with (131)I-MN-14 F(ab)2 is well tolerated and shows evidence of biochemical and radiologic antitumor activity. HAMA development suggests that humanized MAbs will be required in trials with repeated dose schedules. Further dose escalation, alone or in combination with other therapy modalities, is indicated for future trials, preferably with humanized anti-CEA MAbs.     

Gastrointestinal Kaposi's sarcoma in renal transplant patients

We report nine cases of gastrointestinal Kaposi's sarcoma in renal transplant patients negative for human immunodeficiency virus. In eight the lesions regressed on either withdrawing or reducing the dose of cyclosporin A, but this led to the loss of the renal graft in approximately 50 per cent of patients.     

Bipyridylium herbicide toxicity: effects of paraquat and diquat on isolated rat hepatocytes

Paraquat (1,1'-dimethyl-4,4'-bipyridylium) and diquat (1,1'-ethylene-2,2'-bipyridylium) are the two most widely used bipyridylium herbicides today. Both compounds, however, have also been found to cause liver damage in animals and man. In this study, isolated rat hepatocytes were used to assess the cytotoxicity of these two compounds. Five indices of cell damage were used to quantitate cytotoxicity: dye (trypan blue) uptake, loss of cell respiration, the extracellular release of lysosomal enzymes, the formation of thiobarbiturate (TBA)-reacting substances, and the oxidation of cellular NADH and NADPH. Diquat was shown to be more toxic than paraquat toward these cells in the first three assay systems. The acute LC50 for diquat was determined to be 80 mM, whereas the acute LC50 for paraquat was estimated to be greater than 1 M. This difference in cell sensitivity could be explained, at least in part, by the observed differences in herbicide uptake rates for these two compounds. Diquat uptake was calculated to be 9.0 +/- 1.1 nmoles/hour/10(6) cells, whereas paraquat uptake was only 5.5 +/- 0.5 nmoles/hour/10(6) cells. The dose-response curves for enzyme release and loss of cell respiration superimposed the lethality curves for both compounds. An oxidative mechanism of cytotoxicity was suggested for diquat by: the establishment of both a concentration-dependent and a time-dependent increase in lipid peroxidation (formation of TBA-reacting substances); complete oxidation of both NADPH and NADH at herbicide levels less than the LC50; and the finding that diquat stimulated glucose oxidation at subtoxic doses.