The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study.

The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.     

Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects.

The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma. Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n = 7) or saline (n = 5) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis. Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBT-induced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure. In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.     

Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

Safety considerations for operating room personnel during hyperthermic intraoperative intraperitoneal chemotherapy perfusion.

The new treatment strategy for Peritoneal Surface Malignancy combines a cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cytoreduction removes all macroscopic tumor. Intraperitoneal chemotherapy avoids implantation of microscopic residual tumor cells on intra-abdominal surfaces when it is administered intraoperatively and/or early in the postoperative period. Delivering cytotoxic drugs directly into the peritoneal cavity maximizes dose intensity and minimizes systemic toxicity. Hyperthermia is selectively cytotoxic for malignant cells and potentiates the effect of chemotherapy. Implementation of this procedure makes the perioperative personnel to face a risk of exposure to cytotoxic agents. Furthermore, peritonectomies and electro-evaporation of tumor nodules are performed with high voltage electrocautery, generating a large amount of surgical smoke during several hours. Inhalation of these fumes may be also a risk for healthcare workers. In this article, we analyse in depth these new risks of the operating room personnel, we review the literature, and we give guidelines for secure performance of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy, as well as for early postoperative intraperitoneal chemotherapy administration. These new procedures are safe techniques for patients and healthcare workers provided adequate policies are adopted to avoid occupational exposure.     

Effects of intranasal 17beta-estradiol and raloxifene on lipid profile and fibrinogen in hypercholesterolemic postmenopausal women: a randomized, placebo-controlled clinical trial.

AIM: To compare the effects of 17beta-estradiol given intranasally (intranasal E2) and raloxifene on serum lipid profile and fibrinogen in hypercholesterolemic postmenopausal women. METHODS: The study population consisted of 46 women after menopause. The placebo group (n = 11) was given calcium, while the intervention groups were given intranasal E2 (Aerodiol; Servier, Chambray-les-Tours, France) (n = 16) or raloxifene (Evista; Lilly SA, Madrid, Spain) (n = 19). Blood lipids and fibrinogen were compared between groups at baseline and after 3 months of treatment. RESULTS: The group receiving intranasal E2 showed a significant decrease in triglyceride levels (p<0.05) and a marked increase in high-density lipoprotein cholesterol levels (p<0.05). No changes in lipid profile were observed in the raloxifene and placebo groups. Raloxifene caused a significant decrease in fibrinogen levels (p<0.05). CONCLUSION: Intranasal E2 exerts significant effects on lipid profile in hypercholesterolemic postmenopausal women. Raloxifene has a greater impact on fibrinogen than intranasal E2 application.     

Neuropeptides in idiopathic chronic constipation (slow transit constipation)

Tissue specimens from the large bowel of 18 patients with long-standing slow transit constipation were investigated to determine the distribution and density of several neuropeptides and amines in the enteric nerve system, and also of endocrine cells in comparison to normal individuals. CGRP (calcitonin gene-related peptide), galanin, glucagon, GRP (gastrin-releasing peptide), metenkephalin, motilin, neuropeptide Y (NPY), PACAP, peptide YY (PYY), serotonin, somatostatin, substance P and VIP were studied by immunohistochemistry. Tissue concentrations of VIP, substance P and galanin were also measured by radioimmunoassay. Significantly increased VIP, SP and galanin contents were found in specimens from the ascending colon. Levels of VIP and galanin were also increased in the transverse colon. Immunohistochemistry revealed only marginal changes with an increased density of PACAP nerve fibres in the smooth muscle and of VIP and PACAP nerves in the myenteric plexus of the transverse colon. In the descending colon substance P and NPY immunoreactivity were also increased in the myenteric plexus while the density of VIP nerve fibres was reduced in the mucosa/submucosa. The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients.     

How to assess fetal metabolic acidosis from cord samples.

The degree of metabolic acidosis at birth has been calculated in cord artery and vein samples from 21 term fetuses with cord artery pH less than 7.20. The aim of the study was to compare base deficit values calculated from either Siggaard-Andersen alignment nomogram (BD blood) or the Acid-Base chart (BD extra cellular fluid, BDecf). BDblood was found to be consistently higher in the cord artery as compared with BDecf, 13.2 +/- 3.5 and 9.9 +/- 2.9 mmol/l (Mean +/- SD), respectively. A significant correlation was found between cord artery PCO2 and BDblood whereas BDecf appeared unaffected by PCO2. In cases with cord entanglement BDecf a-v differences were increased to 3.4 +/- 2.3 mmol/l as compared with the small a-v difference noted in acidotic cases without cord entanglement, 1.1 +/- 1.25 mmol/l. It is speculated that with acutely emerging, intermittent asphyxia due to cord compression, a cord artery and vein difference in metabolic acidosis may exist and where the vein captures the basal level and the artery the acute changes. It is concluded that BDecf in both cord artery and vein add valuable information on the mechanisms behind metabolic acidosis.