Molecular cytogenetic analysis of a de novo 5q31q33 deletion associated multiple congenital anomalies: case report

Interstitial deletions are relatively rare chromosomal anomalies that usually arise de novo. The data describing the phenotype associated with interstitial deletions of 5q are very limited. We describe the first case of multiple fetal anomalies, diagnosed on prenatal sonographic examination, associated with a deletion at 5q31q33. Sonographic examination at 23 weeks' gestation demonstrated growth parameters consistent with 20 weeks' gestation; a 7-mm nuchal fold; a dilated loop of bowel adjacent to the stomach suggestive of duodenal atresia; clubbing of the left foot; a narrow aorta; suspected ventricular septal defect; and placental thickening. The patient delivered a severely growth-restricted fetus and enlarged placenta at 30 weeks' gestation. The infant died neonatally.     

A prospective evaluation of the value of preoperative laboratory testing for office anesthesia and sedation

PURPOSE: The purpose of this investigation was to determine whether routine laboratory testing affected the clinician's preoperative evaluation and decision-making process for patients undergoing general anesthesia or intravenous sedation in the oral and maxillofacial surgery office. PATIENTS AND METHODS: This was a prospective evaluation of the records of 458 who required an office general anesthetic or intravenous sedation for routine dentoalveolar surgery. The patients ranged in age from 15 to 54 years and were categorized as American Society of Anesthesiologists Classification I or II. Fifty-two percent were female. All patients underwent a history and physical examination, complete blood cell count, and urine analysis. Female patients were tested for pregnancy by measuring the serum beta human chorionic gonadotropin level. All patients older than 40 years of age were further evaluated by posterior-anterior and lateral chest radiographs, as well as electrocardiography. On the day of surgery, the data were reviewed and analyzed, and specific components of the history were reassessed. The results of the decision-making process were evaluated by one investigator. RESULTS: From the 458 patients initially enrolled, 78 failed to return on the appointed day. Of the 235 patients requiring general anesthesia who did return on the appointed day, five had aberrant laboratory values (2%). These consisted of one patient with a low hematocrit, one with a low red blood cell count, one with a low white blood cell count, and two with a urine analysis positive for blood. No procedure was canceled based on the aberrant data. Of the 145 patients requiring intravenous sedation who did return on the appointed day, six had aberrant laboratory values (4%). Two patients exhibited elevated white blood cell counts, two possessed low red blood cell counts, one known to have diabetes had an elevated urine glucose, and one patient with an elevated human chorionic gonadotropin level realized that her menstrual cycle was delayed. The latter two patients had their procedures deferred. CONCLUSIONS: Based on the results of this study, a good history and physical examination and then reassessment of key portions of the history were the major factors in the development of the anesthetic treatment plan. Laboratory data had little if any effect on the decision-making process.     

The expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) on human vascular smooth muscle cells and monocytes and its down-regulation by lovastatin

Accumulation of oxidatively modified low-density lipoprotein (oxLDL) in the vascular wall is a characteristic feature of atherosclerosis. oxLDL can be taken up into monocytes, smooth muscle cells, and endothelial cells by several known scavenger receptors such as scavenger receptor class A I and II, CD36, and CD68. A new lectin-like oxLDL receptor (LOX-1) was recently found in bovine and human endothelial cells. We studied whether LOX-1 is also expressed in other cells present in the atherosclerotic lesion and whether its expression can be modified. We found LOX-1 expression in human blood monocytes, umbilical smooth muscle and endothelial cells, and 3T3 fibroblasts. LOX-1 mRNA expression in monocytes could be significantly suppressed by lovastatin. Thus, LOX-1 expression is not restricted to endothelial cells and its down-regulation by HMG-CoA reductase inhibitors could contribute to the clinical benefits of these drugs.     

Microelectrode recording during posteroventral pallidotomy: impact on target selection and complications

OBJECTIVE: To assess the practical usefulness of single-cell microelectrode recording (MER) when performing posteroventral pallidotomy. METHODS: A retrospective comparison of the initial, magnetic resonance imaging-derived coordinates of the pallidotomy target to the final, MER-refined lesion coordinates in 132 consecutive pallidotomies was conducted. The time required to perform the procedure and the surgical complications are reported. RESULTS: MER led to targeting changes in 98% of the cases. In 12%, the MER-refined target was more than 4 mm from the original, image-guided site, which is a targeting error that could adversely affect outcome. Although all components of targeting were affected by MER, laterality and depth were impacted most. The ventral border of the globus pallidus pars interna was located within 1 mm of the magnetic resonance imaging-selected target in only 40% of the cases. On average, only 2.2 MER trajectories were required to perform pallidotomy. During the last 3 years of our study, 85% of the procedures were performed with one or two trajectories. The mean operating time of the operations performed during the last 3 years was 2 hours and 12 minutes. The incidence of intracerebral hemorrhage in our series (1.5%) was no higher than that reported for other large series of stereotactic procedures. No patient suffered an optic tract injury. CONCLUSION: MER provides important targeting information for performing pallidotomy. In particular, the micrometric delineation of the ventral border of the globus pallidus pars interna permits safe lesioning of the posteroventral region of the globus pallidus pars interna with little risk of visual field deficit. These data can be obtained efficiently and without increased surgical risk.     

Phase II trial of chemoembolization for the treatment of metastatic colorectal carcinoma to the liver and review of the literature

BACKGROUND: Hepatic artery chemoembolization represents an alternative treatment for patients whose neoplastic lesions are not amenable or have become refractory to other treatment modalities. This project was designed to test the feasibility of regional chemoembolization for patients with colorectal carcinoma metastasis to the liver who had experienced failure with one or more systemic treatments. METHODS: Thirty patients who met the study entry criteria underwent one to three hepatic artery chemoembolizations. The chemoembolization regimen consisted of an injection of a bovine collagen material with cisplatin (10 mg/mL), doxorubicin (3 mg/mL), and mitomycin C (3 mg/mL). Repeat treatments were performed at 6- to 8-week intervals. RESULTS: Radiologic responses, as measured by a decrease in lesion density of at least 75% of the lesion or a 25% decrease in the size of the lesion, occurred in 63% of the cases. A decrease of at least 25% of the baseline carcinoembryonic antigen level occurred in 95% of the cases. All responses were transient. Median survival for all 30 patients was 8.6 months after the initiation of chemoembolization and 29 months after the initial diagnosis of metastasis to the liver. Common toxicities included a "postembolization syndrome," which consisted of fever > 101 degrees F (83%), pain in the right upper quadrant (100%), nausea, and vomiting. Lethargy was a common occurrence (in 60+% of cases) and lasted up to 6 weeks. Hematologic toxicities included leukocytosis, anemia, and thrombocytopenia. CONCLUSIONS: Chemoembolization is a feasible treatment modality for patients with colorectal carcinoma metastasis to the liver who have experienced failure with other systemic treatments. It results in high response rates with transient mild-to-moderate toxicity. Responses are measured in months, however, and all patients have eventual progression of disease. Patients who are able to undergo three or more chemoembolization procedures may receive the most clinical benefit.     

Empirical solvent-mediated potentials hold for both intra-molecular and inter-molecular inter-residue interactions

Whether knowledge-based intra-molecular inter-residue potentials are valid to represent inter-molecular interactions taking place at protein-protein interfaces has been questioned in several studies. Differences in the chain connectivity effect and in residue packing geometry between interfaces and single chain monomers have been pointed out as possible sources of distinct energetics for the two cases. In the present study, the interfacial regions of protein-protein complexes are examined to extract inter-molecular inter-residue potentials, using the same statistical methods as those previously adopted for intra-molecular residue pairs. Two sets of energy parameters are derived, corresponding to solvent-mediation and "average residue" mediation. The former set is shown to be highly correlated (correlation coefficient 0.89) with that previously obtained for inter-residue interactions within single chain monomers, while the latter exhibits a weaker correlation (0.69) with its intra-molecular counterpart. In addition to the close similarity of intra- and inter-molecular solvent-mediated potentials, they are shown to be significantly more residue-specific and thereby discriminative compared to the residue-mediated ones, indicating that solvent-mediation plays a major role in controlling the effective inter-residue interactions, either at interfaces, or within single monomers. Based on this observation, a reduced set of energy parameters comprising 20 one-body and 3 two-body terms is proposed (as opposed to the 20 x 20 tables of inter-residue potentials), which reproduces the conventional 20 x 20 tables with a correlation coefficient of 0.99.     

Monoclonal antibodies to mitochondrial E2 components define autoepitopes in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of antimitochondrial Abs (AMA). The autoantigens recognized by AMA are the E2 components of the pyruvate dehydrogenase complex (PDC-E2), the branched chain 2-oxoacid dehydrogenase complex E (BCOADC-E2), and the 2-oxoglutarate dehydrogenase complex E (OGDC-E2). Previous studies using murine monoclonal and human combinatorial Abs to PDC-E2 have demonstrated an intense linear staining pattern in the apical region of biliary epithelial cells (BEC) in PBC but not control liver. We therefore examined whether mAbs to the other mitochondrial autoantigens BCOADC-E2 and OGDC-E2 demonstrated disease-specific patterns of reactivity. Using an expressed recombinant "trihybrid" protein containing the lipoyl domains of PDC-E2, OGDC-E2, and BCOADC-E2, we immunized BALB/c mice to produce 35 mAbs specific for one or more of the above mitochondrial autoantigens. Seven of these mAbs uniquely stained the apical region of BEC in PBC. Of these seven, one was reactive to PDC-E2, two recognized BCOADC-E2, three were reactive to OGDC-E2, and one recognized all three Ags. Our current data demonstrate that, similar to our previous studies regarding PDC-E2, mAbs to BCOADC-E2 and OGDC-E2, or a molecule that cross-reacts with the inner lipoyl domain of all three enzymes, also show a uniquely intense staining pattern in the apical region of BEC in patients with PBC when compared with diseased controls. The abundance of such disease-specific determinants in the target cells of PBC raises interesting possibilities regarding the role of these autoantigens in the pathogenesis of this disease.