Revisit on congenital bronchopulmonary vascular malformations: a haphazard branching theory of malinosculations and its clinical classification and implication.

We propose a haphazard branching theory to support the concept of bronchopulmonary malinosculations, and we apply this theory to classify congenital bronchopulmonary vascular malformation (BPVM) based on the anatomical results we have found. Between January 1990 and December 1997, a total of 22 pediatric patients (10 male and 12 female), aged 2 days to 14 years (median, 19.6 months), with congenital BPVM were enrolled in this retrospective study. Study modalities include the clinical features and plain chest films (n = 22) plus at least two of the following: echocardiography (n = 13), barium esophagraphy (n = 2), bronchoscopy (n = 4), contrast bronchography (n = 8), high-resolution direct coronal CT (n = 1) and electron beam or ultrafast CT (n = 1) of the chest, MRI (n = 10), MRA (n = 1), contrast cineangiocardiography (n = 9), surgery (n = 11), or autopsy (n = 2). The salient clinical features were recurrent lung infections in 14 patients, acute respiratory distress in 13, associated cardiovascular malformations in 8, dextroversion in 7, congestive heart failure in 7, dextrocardia in 4, and complex congenital heart diseases in 4. There were abnormal openings (malinosculations) of the pulmonary airway in 20 patients: to an artery in 12, to a vein in 8, and to the lung parenchyma in 9. These 22 patients with congenital BPVM can be classified into bronchial malinosculation (10 cases), arterial malinosculation (2 cases), and bronchoarterial malinosculation (10 cases). Congenital BPVM can be classified in terms of bronchopulmonary malinosculation based upon a haphazard branching theory, in which abnormal communications between two independent systems (primitive foregut system and aortic-pulmonary arch system) occurred coincidentally rather than causally.     

Carrier diagnosis of Duchenne muscular dystrophy using restriction fragment length polymorphisms

Molecular probes that are tightly linked to and flank the Duchenne muscular dystrophy (DMD) locus, have been used to characterize DMD mutations and diagnose female carriers. Deletions within the Xp21 region were identified for 8 of 71 families studied. Using both DNA and CK studies, accurate (96 to 98%) carrier or noncarrier diagnoses were made for 51 of 75 females at risk in 24 families with a single affected male. DNA studies resulted in an alteration of predicted risk in 40% of the cases. Recombinant diagnostic methods are useful for carrier detection in families with one or more affected males.     

Reduced expression of CD69 and adhesion molecules of T lymphocytes in asthmatic children receiving immunotherapy

T lymphocytes play a fundamental role in the initiation and regulation of chronic inflammatory responses in patients with asthma. CD69 is an early marker of T‐cell activation. The levels of intercellular adhesion molecule‐1 (ICAM‐1, CD54) and L ‐selectin have been reported to increase in patients with allergic diseases and asthma. The present study was therefore undertaken to investigate the expression of CD69, CD54, and L ‐selectin by T lymphocytes of children with asthma, before and after immunotherapy. Eighteen children newly diagnosed with asthma, 11 good and nine poor responders to immunotherapy, and 16 normal subjects, were enrolled in this study. The percentages of CD69⁺, CD54⁺, and CD62L⁺ cells in T lymphocytes were measured by using flow cytometry. The levels of CD69, CD54, and CD62L in serum and culture supernatants were determined by using enzyme‐linked immunosorbent assay (ELISA). The expression of CD69 and CD54 on CD3⁺ T lymphocytes was significantly higher in children with asthma than in control patients. All the patient groups expressed (spontaneously and following stimulation with phorbol myristate acetate and ionomycin together with mite‐extract proteins) greater amounts of CD69 and CD54 than did control subjects. With long‐term immunotherapy, the percentages of CD69⁺ and CD54⁺ T lymphocytes were significantly lower in patients with a good response to immunotherapy. Our results also showed significantly lower serum L ‐selectin levels following immunotherapy. In conclusion, successful immunotherapy resulted in decreased expression and production of CD69 and CD54. These results may explain, in part, the clinical efficacy of immunotherapy.     

Activated neutrophils aggravate endothelial dysfunction after reperfusion of the ischemic feline myocardium.

Endothelial dysfunction, as evidenced by decreased stimulated release of endothelium-derived relaxing factor (EDRF), occurs after reperfusion of the ischemic myocardium. To better understand this endothelial dysfunction, isolated cat hearts were perfused under constant flow by the Langendorff procedure with Krebs-Henseleit solution devoid of blood cells. Following global ischemia (90 minutes) and reperfusion (20 minutes), coronary vasorelaxation to the endothelium-dependent vasodilator acetylcholine (ACh) was 70 +/- 3% of initial values (p less than 0.01) compared with 90 +/- 4% in nonischemic control perfused hearts. No decrement occurred in response to the endothelium-independent vasodilator nitroglycerin (NTG). Coronary artery rings isolated from the ischemic left circumflex coronary artery showed a similar degree of endothelial dysfunction to ACh, with normal relaxation in response to NaNO2. Autologous cat neutrophils (100 million cells), activated with 100 nmol/L f-met-leu-phe infused into the heart directly before and throughout reperfusion, resulted in a further decrement in ACh-induced vasodilation, to 55 +/- 5% of initial response, with no effect on NTG-induced vasodilation. Similar results were obtained with coronary artery rings isolated from perfused cat hearts and exposed to neutrophils. This neutrophil-enhanced endothelial dysfunction was inhibited by human superoxide dismutase as well as by an antibody to the adherence glycoprotein complex CD-18 (i.e., MAbR 15.7). Therefore endothelial dysfunction occurs initially upon reperfusion of the previously ischemic heart and is aggravated by superoxide radicals produced by activated neutrophils.     

Monoclonal antibody K1 reacts with epithelial mesothelioma but not with lung adenocarcinoma.

Immunoperoxidase histochemical staining of cryostat sections from human tumor tissues revealed that a murine monoclonal antibody (MAb), K1, can distinguish epithelial mesotheliomas from lung adenocarcinomas. All of 15 epithelial-type mesotheliomas and all four mixed type mesothelioma samples, but none of 23 lung adenocarcinomas with different degrees of histologic differentiation demonstrated reactivity with antibody K1. Of the cell populations in each mesothelioma tested, 80% to 100% showed strong and homogeneous staining with MAb K1. Immunofluorescence analysis of live cultured cells from an epithelioid mesothelioma (H-meso) and several lung carcinoma cell lines as well as a pleural effusion of a patient with mesothelioma also showed selective reactivity of K1 with the mesothelioma cells. These data indicate that K1 can be useful as a mesothelial cell marker for the differential pathological diagnosis of the epithelial form of mesothelioma; K1 may also be useful in the study of the pathogenesis, immunodiagnosis, and immunotherapy of epithelial-type and mixed-type human malignant mesothelioma.     

Results of the tension-free vaginal tape procedure for stress incontinence: Patient''s perspective

BACKGROUND: To evaluate the results of the tension-free vaginal tape procedure (TVT) from a patient's perspective. METHODS: Between May 1999 and January 2002, 90 patients underwent a TVT for genuine stress incontinence (GSI) and mixed incontinence. Prior to the procedure, GSI was confirmed by clinical examination and urodynamic studies. Results were then audited from patient notes and the same patients were sent questionnaires to examine results from a patient perspective. RESULTS: Overall response rate to the questionnaire was 70 (77%). The mean age of the patients was 50.4 years (range 31-83 years). Sixty-one patients had spinal anesthesia, seven had general anesthesia and two had local anesthesia. Mean hospital stay was 3.36 days (range 2-14 days) and mean period from the operation to the time of the survey and audit was 16.34 months (range 3-28; SD 6.92). Thirty-nine (56%) of the 70 patients who answered said that the operation had cured their incontinence, 16 (23%) had an improvement in their symptoms, 7 (10%) had worsening of their symptoms and 8 (11%) felt that the operation did not make any difference. The overall success rate according to the patients' perspective was 79%, whereas our audit showed an overall success rate of 86% (77% and 82%, respectively, when we compared only the 66 patients who had both notes and replies available for analysis). CONCLUSION: Although a patient's perception regarding the success of TVT tends to differ from that of a clinician, it was not found to be statistically significant (P = 0.22, McNemar test). The TVT is a very successful operation, but realistic cure rates should be offered to patients.     

Hodgkin disease: CT of the thymus

The computed tomography (CT) scans in two groups of patients with Hodgkin disease were reviewed to determine the frequency of thymic enlargement. In 50 CT scans from 50 patients with evidence of thoracic disease on CT scans who were examined for primary staging, the thymus was enlarged in 15 of 50 (30%). Fifty CT scans were obtained from 44 patients at the time of 50 separate episodes of known or suspected relapse. Relapse occurred in the mediastinum in 12 episodes, lung parenchyma in five, and both sites in one. Thymic enlargement thought to be due to involvement by disease was present in seven of 18 (38%). Mediastinal disease was associated with thymic enlargement in all but one patient in whom a thymic cyst developed after radiation therapy. Differentiation of thymic enlargement from enlarged superior mediastinal lymph nodes was easily made in all but two patients. Thymic enlargement in the absence of lymph node enlargement may indicate a different disease, since isolated Hodgkin disease of the thymus is uncommon. Primary thymic tumor should be considered initially, whereas after treatment, rebound hyperplasia of the thymus may be the cause of enlargement.     

Solid and papillary epithelial neoplasms of the pancreas: CT findings

Five female patients and one male patient with solid and papillary epithelial neoplasms of the pancreas were examined with computed tomography (CT). The mean age of the patients was 27 years (range, 13-46 years). All cases showed well-encapsulated, round or lobulated masses consisting of both cystic and solid areas. Cystic portions showed CT numbers that suggested hemorrhagic necrosis. There were no internal septations within the masses. In three tumors located in the head of the pancreas, dilatation of the biliary tree was absent or minimal, although the masses were large. Two tumors contained calcifications. One tumor demonstrated metastatic deposits in liver and lymph nodes. Metastatic masses appeared similar to the primary pancreatic mass. Solid and papillary neoplasm of the pancreas should be the primary diagnostic consideration when characteristic CT findings are detected in a young female patient.     

In vitro metabolic study of temsirolimus: preparation, isolation, and identification of the metabolites.

The in vitro metabolism of temsirolimus, (rapamycin-42-[2,2-bis-(hydroxymethyl)]-propionate), an antineoplastic agent, was studied using human liver microsomes as well as recombinant human cytochrome P450s, namely CYP3A4, 1A2, 2A6, 2C8, 2C9, 2C19, and 2E1. Fifteen metabolites were detected by liquid chromatography (LC)-tandem mass spectrometry (MS/MS or MS/MS/MS). CYP3A4 was identified as the main enzyme responsible for the metabolism of the compound. Incubation of temsirolimus with recombinant CYP3A4 produced most of the metabolites detected from incubation with human liver microsomes, which was used for large-scale preparation of the metabolites. By silica gel chromatography followed by semipreparative reverse-phase high-performance liquid chromatography, individual metabolites were separated and purified for structural elucidation and bioactivity studies. The minor metabolites (peaks 1-7) were identified as hydroxylated or desmethylated macrolide ring-opened temsirolimus derivatives by both positive and negative mass spectrometry (MS) and MS/MS spectroscopic methods. Because these compounds were unstable and only present in trace amounts, no further investigations were conducted. Six major metabolites were identified as 36-hydroxyl temsirolimus (M8), 35-hydroxyl temsirolimus (M9), 11-hydroxyl temsirolimus with an opened hemiketal ring (M10 and M11), N- oxide temsirolimus (M12), and 32-O-desmethyl temsirolimus (M13) using combined LC-MS, MS/MS, MS/MS/MS, and NMR techniques. Compared with the parent compound, these metabolites showed dramatically decreased activity against LNCaP cellular proliferation.