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Biomedical subjects

M Lewin

Publications and source records attributed to M Lewin.

At least 37 records · Page 2Linked to original sources

Cystogastric transmural drainage for the treatment of symptomatic cystic metastases from ovarian carcinoma.

Approximately 80% of ovarian cancers are discovered when they have already progressed to stage III or IV lesions. The prognosis is, therefore, poor despite intensive treatment. Intraperitoneal dissemination is one of the most frequent pathways of distant spread ovarian cancer and pseudocystic metastases usually occur. When such cystic metastases remain symptomatic despite antitumor treatment, viable options are limited because palliative surgery generates high operative morbidity and mortality. For many years, in patients in whom the risks associated with surgery are high, percutaneous drainage and sclerosis under radiologic guidance has been performed as an effective alternative option for various forms of abdominal fluid collection. Such a collection in pancreatic pseudocyst benefits from cystogastric transmural drainage to avoid external drainage and achieves the same results as surgical cystogastrostomy. We report this transmural drainage technique under image guidance used to drain a symptomatic cystic metastasis, which was compressing the stomach.

Ascitic Fluid↗

Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues of murine genes implicated in left-right axis development.

Members of the transforming growth factor (TGF)-beta family of cell-signaling molecules have been implicated recently in mammalian left-right (LR) axis development, the process by which vertebrates lateralize unpaired organs (e.g., heart, stomach, and spleen). Two family members, Lefty1 and Lefty2, are expressed exclusively on the left side of the mouse embryo by 8.0 days post coitum. This asymmetry is lost or reversed in two murine models of abnormal LR-axis specification, inversus viscerum (iv) and inversion of embryonic turning (inv). Furthermore, mice homozygous for a Lefty1 null allele manifest LR malformations and misexpress Lefty2. We hypothesized that Lefty mutations may be associated with human LR-axis malformations. We now report characterization of two Lefty homologues, LEFTY A and LEFTY B, separated by approximately 50 kb on chromosome 1q42. Each comprises four exons spliced at identical positions. LEFTY A is identical to ebaf, a cDNA previously identified in a search for genes expressed in human endometrium. The deduced amino acid sequences of LEFTY A and LEFTY B are more similar to each other than to Lefty1 or Lefty2. Analysis of 126 human cases of LR-axis malformations showed one nonsense and one missense mutation in LEFTY A. Both mutations lie in the cysteine-knot region of the protein LEFTY A, and the phenotype of affected individuals is very similar to that typically seen in Lefty1-/- mice with LR-axis malformations.

Amino Acid Sequence↗

Hepatic nodules in Budd-Chiari syndrome: imaging features.

PURPOSE: To analyze the imaging features of nodules associated with Budd-Chiari syndrome. MATERIALS AND METHODS: The authors retrospectively studied images obtained in 23 patients with liver nodules who were being followed up for Budd-Chiari syndrome. Doppler ultrasonography was performed in all patients, computed tomography in 16, and magnetic resonance (MR) imaging in 20. The following lesion features were evaluated: location, number, size, vascularization, qualitative signal intensity at MR imaging, and homogeneity. Nodules were diagnosed on the basis of histopathologic findings or clinical and biologic data with no change at imaging during 2-year follow-up. RESULTS: All patients had histopathologic features of chronic Budd-Chiari syndrome. Four patients had hepatocellular carcinoma (HCC), with one to three lesions. The mean diameter of the largest HCC lesion in each patient was 7.3 cm. All HCC lesions were heterogeneous and had high signal intensity on T2-weighted MR images. Nineteen patients had multiple benign regenerative nodules, most of which were smaller than 4 cm. Most nodules were homogeneous and hyperintense on T1- and T2-weighted images. In 15 patients, nodules were hypervascular in the arterial phase. CONCLUSION: In patients with chronic Budd-Chiari syndrome, multiple (> 10) small (< 4-cm) lesions are suggestive of benignity.

Adult↗

Contrast agents in magnetic resonance imaging of the liver: present and future.

New contrast agents are being developed by drug companies to better image the liver magnetic resonance imaging (MRI). They can be divided into hepatobiliary agents (Gd-EOB-DTPA, Gd-BOPTA, Mangafodipir) and nanoparticulate agents directed to the reticulo-endothelial system (ferumoxides, SHU 555A). After intravenous injection, all these agents concentrate in the liver and induce profound signal changes. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver-lesion conspicuity is enhanced, leading to a better visualization of the lesion. After a description of the principal pharmacokinetic characteristics of the compounds, this review paper summarizes the utility of the agents in the detection and characterization of focal liver diseases.

Contrast Media↗

In vitro model(s) for the percutaneous delivery of active tissue repair agents.

There is a need to evaluate the permeability of human ulcerated tissue and periulcer tissue in order to assess the possible treatment of such a localized pathological lesion with a topical therapy. In vitro percutaneous absorption studies were undertaken to evaluate an animal model that may mimic this clinical situation. Porcine skin from three anatomical sites, the ear, abdomen, and dorsum; ischaemic skin (porcine and guinea pig); porcine wounds; and human skin (including periulcer and ulcerated tissue) were investigated, utilizing both whole skin and dermal membranes. Dermal membranes were chosen as representative of ulcerated tissue, as there would be no epidermal barrier present, and the thickness of the dermal membrane was not expected to offer any diffusional resistance to topically applied active agents. A range of chemicals with differing physicochemical properties was investigated using a Franz type diffusion cell. For all tissues a permeability coefficient (kp with units of cm h-1) was measured, along with skin thickness and tissue partition coefficient measurements. Under these experimental conditions and for the range of compounds tested, the results suggest that porcine skin, whole skin, and dermal membranes should be considered as good representative in vitro models for the topical delivery of compounds to human skin and ulcerated tissue, respectively.

Administration, Cutaneous↗

Evaluation of failure to follow vaccination recommendations as a marker for failure to follow other health recommendations.

OBJECTIVE: To determine whether families who fail to vaccinate their children also fail to follow other health recommendations. SETTING: US civilian noninstitutionalized population. DESIGN: National survey with a stratified cluster design. PARTICIPANTS: Adult respondents for children 19 to 35 months of age surveyed in the 1991 National Health Interview Survey with documented vaccination history. MEASUREMENTS: Comparison of responses to 23 questions related to health behaviors between respondents of up-to-date (UTD), i.e. having received 4 doses of diphtheria and tetanus toxoids and pertussis vaccine, 3 doses of polio vaccine and one measles vaccine, and non-UTD children. RESULTS: Of the 781 studied children, non-UTD (n = 357) and UTD (n = 424) children, or their respondents, did not differ in 18 of the 23 studied health behaviors. However, although non-UTD and UTD children were equally likely to have car seats, non-UTD children were less likely to use them always (84.3% vs. 92.9%, P = 0.002). National Health Interview Survey respondents of non-UTD children were more likely than their counterparts never to read food labels for ingredients (28.9% vs. 20.5%, P = 0.04) or for fat/cholesterol content (33.6% vs. 22.3%, P = 0.02) and never to buy low salt foods (37.5% vs. 21.5%, P = 0.001). Multivariate analyses showed that parental education level, not a child's vaccination status, was associated with compliance with the studied health behaviors. CONCLUSION: Failure to vaccinate children on time is not consistently related to the likelihood of family member's following of other health recommendations. However, these data suggest that although mediated via parental educational levels, a child's immunization status helps to define families at risk for poor nutrition-related behaviors and those who are in need of counseling on seat belt use.

Adult↗

Interoceptive exposure versus breathing retraining within cognitive-behavioural therapy for panic disorder with agoraphobia.

This study compared two components of a cognitive-behavioural treatment for panic disorder. Thirty-eight individuals with panic disorder and agoraphobia were randomly assigned to (a) cognitive restructuring, interoceptive exposure (i.e. repeated exposure to feared bodily sensations) and in vivo exposure to agoraphobic situations; or (b) cognitive restructuring, breathing retraining and in vivo exposure to agoraphobic situations. Assessments were conducted at pre-treatment, post-treatment and six months later. The treatments were equally effective on many measures. However, treatment that included interoceptive exposure was more effective at post-treatment in terms of panic frequency, overall severity and functioning, and more effective at six-month follow-up in terms of panic frequency, phobic fears and general anxiety and functioning. Follow-up results were limited due to attrition.

Adolescent↗

[Non-surgical treatment of biliary stenoses after hepatic transplantation].

We report the initial and long-term results of non surgical procedures performed for the treatment of biliary strictures in liver transplant patients. Twelve liver transplant patients with biliary strictures underwent 16 interventional radiological procedures. Initial technical success was achieved in 11 of 12 patients (91%). Within long-term, with a follow-up of 27 months, primary success rate (only one procedure) was 58% (7 of 12 patients). Three restenoses occurred. They were all treated by interventional radiological procedures. The secondary success rate (one or more procedures) was 83% (10 of 12 patients). Two complications occurred including one pancreatitis and one cholangitis. Non surgical management may be performed for patients with biliary strictures after liver transplantation.

Adult↗

[Imaging of a case of wirsungorrhagia].

We report a case of wirsungorrhagia related to rupture of a pseudoaneurysm into the duct of Wirsung in a patient with chronic pancreatitis. Upper gastrointestinal endoscopy showed blood coming from the papilla of Vater suggesting wirsungorrhagia. Non-contrast computed tomography showed a spontaneous hyperdensity and arteriography showed an extravasation of contrast within a very large duct of Wirsung confirming wirsungorrhagia. Arteriography and dynamic computed tomography revealed a pseudoaneurysm from the left gastric artery. The pseudoaneurysm was successfully embolized with four steel microcoils, after super-selective catheterization of small branch of the left gastric artery, keeping gastric and liver vascularization.

Aneurysm, False↗

[Imaging of primary hepatic pheochromocytoma].

Extra-adrenal pheochromocytoma are extremely uncommon tumors. They demonstrate abdominal (97% of the cases), thoracic, vesical or cervical localizations. We report the case of a hepatic pheochromocytoma in a young patient with a post history of labile arterial hypertension. Ultrasonography, computed tomography and magnetic resonance imaging features were similar to those of adrenal pheochromocytoma. The presence of neuroendocrine cells was supported by immunohistochemical criteria. Histological observation showed a lack of local extension. In addition, four years after surgery, there was no apparent clinical syndrome suggesting tumor recurrence or metastasis occurrence. These observations supports the diagnosis of non malignant, primary hepatic pheochromocytoma. To our knowledge, this is the first radiologic description of this kind of tumor.

Adult↗

[Imaging of peritoneal mesotheliomas].

Peritoneal mesothelioma is a rare, either benign or malignant tumor of the peritoneum. We retrospectively analyzed the imaging features of six malignant and three benign peritoneal mesothelioma. Asbestos exposure was proven in three of the six malignant cases and in none of the three benign cases. Ascites was found in seven patients (78%), peritoneal masses in eight patients (88%), small peritoneal nodules in six patients (66%), parietal peritoneal thickening in six patients (66%), thickened mesentery in five patients (55%) and pleural plaques as well as nodules in one patient. These imaging features support the diagnosis of peritoneal mesothelioma but do not allow differentiation between benign and malignant forms of peritoneal mesothelioma.

Adult↗

[Thrombosis of the renal vein and hemorrhagic rectocolitis].

Renal vein thrombosis was observed in a patient with acute ulcerative colitis complicated by retroperitoneal perforation. Retroperitoneal inflammation related to colonic perforation may constitute a predisposing factor for local thrombosis in combination with coagulation disorders (protein S deficiency).

Adult↗

[Imaging of symptomatic giant hemangioma].

A case of symptomatic giant hemangioma of the liver with fever, anemia, and increased erythrocyte sedimentation rate is reported. Spontaneous hyperdense areas at CT, and high signal-intensity areas at T1-weighted MR images were demonstrated within the hemangioma. Marked hemorrhagic zones demonstrated at pathologic examination may explain these uncommon clinical and imaging features.

Adult↗

Pharmacological aspects of acid secretion.

The secretion of gastric acid is regulated both centrally and peripherally. The finding that H2-receptor antagonists are able to reduce or abolish acid secretion due to vagal, gastrinergic, and histaminergic stimulation shows that histamine plays a pivotal role in stimulation of the parietal cell. In the rat, the fundic histamine is released from the ECL cell, in response to gastrin, acetylcholine, or epinephrine, and histamine release is inhibited by somatostatin or by the H3-receptor ligand, R-alpha-methyl histamine. The parietal cell has a muscarinic, M3, receptor responsible for [Ca]i regulation. Blockade of muscarinic receptors by atropine can be as effective as H2-receptor blockade in controlling acid secretion. However, general effects on muscarinic receptors elsewhere produce significant side effects. The different receptor pathways converge to stimulate the gastric H+,K(+)-ATPase, the pump responsible for acid secretion by the stomach. This enzyme is an alpha,beta heterodimer, present in cytoplasmic membrane vesicles of the resting cell and in the canaliculus of the stimulated cell. It has been shown that acid secretion by the pump depends on provision of K+Cl- efflux pathway becoming associated with the pump. As secretion occurs only in the canaliculus, this K+Cl- pathway is activated only when the pump inserts into the canalicular membrane. Transport by the enzyme involves reciprocal conformational changes in the cytoplasmic and extracytoplasmic domain. These result in changes in sidedness and affinity for H3O+ and K+, enabling active H+ for K+ exchange. The acid pump inhibitors of the substituted benzimidazole class, such as omeprazole, are concentrated in the canaliculus of the secreting parietal cell and are activated there to form sulfenamides. The omeprazole sulfenamide, for example, reacts covalently with two cysteines in the extracytoplasmic loops between the fifth and sixth transmembrane and the seventh and eighth transmembrane segments of the alpha subunit of the H+,K(+)-ATPase, forming disulfide derivatives. This inhibits ATP hydrolysis and H+ transport, resulting in effective, long-lasting regulation of acid secretion. Therefore, this class of acid pump inhibitor is significantly more effective and faster acting than the H2 receptor antagonists. K+ competitive antagonists bind to the M1 and M2 transmembrane segments of the alpha subunit of the acid pump and also abolish ATPase activity. These drugs should also be able to reduce acid secretion more effectively than receptor antagonists and provide shorter acting but complete inhibition of acid secretion.

Amino Acid Sequence↗

Prediction of the antigenic sites of the cystic fibrosis transmembrane conductance regulator protein by molecular modelling.

Antibodies are powerful tools for studying the in situ localization and physiology of proteins. The prediction of epitopes by molecular modelling has been used successfully for the papilloma virus, and valuable antibodies have been raised [Müller et al. (1990) J. Gen. Virol., 71, 2709-2717]. We have improved the modelling approach to allow us to predict epitopes from the primary sequences of the cystic fibrosis transmembrane conductance regulator. The procedure involves searching for fragments of primary sequences likely to make amphipathic secondary structures, which are hydrophilic enough to be at the surface of the folded protein and thus accessible to antibodies. Amphipathic helices were predicted using the methods of Berzofsky, Eisenberg and Jähnig. Their hydrophobic-hydrophilic interface was calculated and drawn, and used to predict the orientation of the helices at the surface of the native protein. Amino acids involved in turns were selected using the algorithm of Eisenberg. Tertiary structures were calculated using 'FOLDING', a software developed by R. Brasseur for the prediction of small protein structures [Brasseur (1995) J. Mol. Graphics, in press]. We selected sequences that folded as turns with at least five protruding polar residues. One important property of antibodies is selectivity. To optimize the selectivity of the raised antibodies, each sequence was screened for similarity (FASTA) to the protein sequence from several databanks. Ubiquitous sequences were discarded. This approach led to the identification of 13 potential epitopes in the cystic fibrosis transmembrane conductance regulator: seven helices and six loops.

Algorithms↗

Peritoneal Kaposi's sarcoma: a cause of ascites in acquired immunodeficiency syndrome.

The investigation of ascites in a homosexual man with acquired immunodeficiency syndrome and mucocutaneous Kaposi's sarcoma (KS) revealed only numerous purplish nodules of KS in the parietal and serosal peritoneum, observed at laparoscopy. KS lesions of the peritoneum, a finding not reported in the literature previously, was the only and likely cause of ascites in our patient. Increased red cells and high serum-ascites albumin gradient in a patient with acquired immunodeficiency syndrome should suggest the possibility of peritoneal KS as a cause of ascites.

Acquired Immunodeficiency Syndrome↗