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Biomedical subjects

A Neuman

Publications and source records attributed to A Neuman.

At least 19 recordsLinked to original sources

Dopamine-induced stress signaling in COS-7 cells transfected with selectively vulnerable muscarinic receptor subtypes is partially mediated via the i3 loop and antagonized by blueberry extract.

Muscarinic receptors (MAChRs) are intimately involved in various aspects of both neuronal and vascular functioning, and there is selective oxidative stress sensitivity (OSS) among MAChR subtypes, with M1, M2, and M4 showing>OSS. OSS was assessed by determining the loss of ability of the cell to extrude or sequester Ca2+ following oxotremorine-induced depolarization following exposure to dopamine (DA) subtypes in transfected COS-7 cells. This OSS can be prevented by pretreatment with blueberry (BB) extract. Present studies were carried out to determine BB treatment of the cells transfected with wild type, truncated or chimeric [where the i3 loop of one receptor was switched with the i3 loop of the other; i.e., M1(M3i3) and M3(M1i3)] receptors would alter DA-induced changes in calcium buffering and would confer protection through alterations in pMAPK, pCREB or PKC signaling. These findings also suggest that BB may antagonize OS effects by lowering activation of pCREB and possibly PKCgamma induced by DA. In the truncated and chimeric receptors, results indicated that BB reduced OSS in response to DA in M1-transfected cells. However, BBs were also effective in preventing these Ca2+ buffering deficits in cells transfected with M1 receptors in which the i3 loop had been removed, but only partially enhanced the protective effects of the M3 i3 loop in the M1(M3i3) chimerics. A similar partial effect of BBs was seen in the M3(M1i3) chimerics which showed increased OSS in response to DA. It appears that antioxidants found in BBs might be targeting additional sites on these chimerics to decrease OSS.

Animals↗

First trimester screening for congenital heart disease.

Most obstetrical practices in the United States offer pregnant women at least one ultrasound during pregnancy. This prenatal ultrasound is usually scheduled at around 18 to 20 weeks gestation. Both the American Institute of Ultrasound in Medicine and the American College of Obstetricians and Gynecologists recommend that the four-chamber view be included to screen for congenital heart disease. Recently, many investigators have attempted to screen for congenital heart disease earlier in pregnancy. Fetal nuchal translucency thickness traditionally used to screen for fetal aneuploidy by transvaginal and abdominal ultrasound has also been shown to identify a large proportion of fetuses with congenital heart disease. Recent studies have also reported congenital heart disease in chromosomally normal fetuses with increased nuchal translucency thickness in the first trimester. Advances in ultrasound technology and training over the last 10 years allow greater visualization rates of the four-chamber view and outflow tracks in the late first trimester (up to 90% visualization at 13 weeks). Fetal echocardiography in the first trimester may be indicated for fetuses at risk for congenital heart disease. In this article we present a review of the most recent and ongoing clinical and basic research to support an earlier first trimester approach to diagnosing congenital heart defects.

Adult↗

Destabilizing effect of a fluorouracil extra base in a hybrid RNA duplex compared with bromo and chloro analogues.

In the presence of cobalt, rhodium or iridium hexammine salts, the RNA/DNA hybrid r-GCUUCGGC-d(X)U (with X = F, Cl or Br) crystallizes as a double-stranded helix with four consecutive G-U and C-U mismatches. The deoxy chloro- and bromouracil derivatives are isomorphous, space group C2, unit-cell parameters a = 53.80, b = 19.40, c = 50.31 A, beta = 109.9 degrees, with the same infinite helix arrangement in the packing along the c axis with one extra DNA halogenouracil base included in the stacking. However, the fluorouracil derivative, with unit-cell parameters a = 53.75, b = 19.40, c = 45.84 A, beta = 105.7 degrees, is not isomorphous. The corresponding extra DNA base d(F)U of the second strand is ejected out of the helical stack, leading to a shortening of the c axis. The specific destabilization of the fluorouracil for the duplex building is analyzed in terms of the polarization effect of the halogen atom attached to the 3'-terminal base that modulates its interactions.

Bromine↗

Second neoplasms in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) has been associated with a high incidence of other skin tumors and hematological malignancies. The purpose of this study was to analyze data from the Israel Cancer Registry regarding the incidence of second neoplasms in patients with MCC and their impact on survival. METHODS: Sixty-seven patients in whom MCC was diagnosed between 1983 and 1999 were included. Data were collected on age, gender and ethnic origin, dates of diagnosis of MCC and any other neoplasm, and date and cause of death, if applicable. Comparison of MCC-specific survival, estimated by the Kaplan-Meier product limit method, between patients with no other neoplasm and those with second primary tumors was performed by log rank test. Age-specific standardized incidence ratio (SIR) was calculated using 5751 age- and ethnic-matched malignant melanoma patients as a control group. RESULTS: Seventeen patients (25%) had a second neoplasm before, concomitant with, or after the diagnosis of MCC; 2 of them also had a third primary tumor. The SIR was 2.8 (95% CI; range, 1.38-4.22), significantly higher than the control group. Almost half the tumors were squamous cell carcinomas, either skin or head and neck, and most of the remainder were hematological malignancies or breast and ovarian adenocarcinomas. On univariate analysis, the presence of another neoplasm, regardless of its chronology, was associated with higher MCC-specific mortality (65% vs. 40% for patients with MCC only; P = 0.022). Analysis of only those patients in whom a second neoplasm developed during follow-up after treatment for MCC yielded an estimated actuarial risk of developing a second primary of 2.1% for each year of observation. CONCLUSIONS: There is a high incidence of second neoplasms, including noncutaneous solid tumors, in patients with MCC. The presence of these neoplasms, whether they appear before, after, or simultaneously with MCC, is associated with a higher MCC-specific mortality.

Adult↗

A pilot study of whole body hyperthermia and carboplatin in platinum-resistant ovarian cancer.

The aim of this study was to determine whether the addition of whole body hyperthermia (WBH) to carboplatin (CBDCA) can induce responses in patients with platinum-resistant ovarian cancer. 16 pretreated patients with platinum-resistant ovarian cancer were entered on a Systemic Hyperthermia Oncological Working Group (SHOWG) study; (14 patients were eligible with 14 evaluable for toxicity and 12 for response). The patients were treated with WBH (Aquatherm) 41.8 degrees C x 60 min in combination with carboplatin (CBDCA) (area under the curve (AUC) of 8) every 4 weeks. Disease status was evaluated every two cycles. Patients were treated for a maximum of six cycles. One patient had a complete response (CR) and 4 had a partial response (PR). 4 patients had stable disease (SD). 3 patients had progressive disease (PD). 2 patients were unevaluable: 1 had a bowel obstruction shortly after her first treatment; the second patient achieved a CR, but only had one treatment secondary to an idiosyncratic reaction to sedative drugs. 2 patients entered on study were ineligible, as they did not meet criteria for platinum resistance; 1 entered a CR and 1 had SD. Dose-limiting toxicity, which required CBDCA dose reductions, was grade 4 thrombocytopenia. Other toxicities included neutropenia (grade 3/4), and nausea and/or vomiting. Consistent with preclinical modelling, these results suggests that 41.8 degrees C WBH can overcome platinum resistance in ovarian cancer. These observations suggest further investigation of the therapeutic potential of WBH in a group of patients who historically fail to respond to salvage therapies is warranted.

Adult↗

Warfarin skin necrosis: local and systemic factors.

Warfarin induced skin necrosis occurs in 0.01-0.1% of warfarin treated patients. The usual presentation is that of painful lesions developing in obese women after the initiation of warfarin treatment. The lesions usually evolve into full thickness skin necrosis within a few days. Although the exact mechanism is not totally clear, low levels of Protein C or S, either functional or inherited, are associated with many of the cases. We report the case of a 17-year-old patient treated with warfarin because of iliofemoral deep vein thrombosis post abortion. The patient developed several huge haemorrhagic blisters on the affected leg. The condition rapidly developed into full thickness skin and fat necrosis. The necrotic lesions were excised and eventually covered with skin graft. The combination of the patient tendency towards hyper-coagulation and the local factors is discussed.

Adolescent↗

[Plagiocephaly in children: etiology, differential diagnosis and helmet treatment].

Plagiocephaly in a head-and-neck irradiated rat model or rhomboid-shaped head, occurs in at least 1 in 300 live births. In most cases such asymmetry is not caused by synostosis of the unilateral coronal or lambdoid sutures, but is rather a deformity produced by intrauterine and/or postnatal deformational forces. Categorization and diagnosis of plagiocephaly as synostotic or deformational is reliably made by physical examination and computerized tomography. Its differential diagnosis is extremely important because prompt surgical correction is usually indicated for the synostotic type. In contrast, infants with deformational frontal or occipital plagiocephaly generally respond to helmet treatment. 10 infants with significant deformational plagiocephaly were treated with individual plastic helmets during the past 2 years and 4 other infants with plagiocephaly are currently being treated. In each instance, cranial asymmetry dramatically improved as the brain grew and the head filled out the helmet. There were no significant complications. Awareness of deformational plagiocephaly allows more accurate diagnosis and appropriate treatment, avoiding unnecessary surgical intervention in patients with positional molding.

Head Protective Devices↗

Salivary gland transplantation: a canine model.

Impaired salivary function with resultant severe dryness of the mouth, or xerostomia, may occur in association with a variety of systemic disorders or therapies. No adequate treatment exists for this debilitating condition, which impedes normal oral function, in particular alimentation and phonation. This study explores the feasibility of salivary gland autotransplantation, using a canine model. A salivary gland with its duct and surrounding blood vessels still attached was excised and reimplanted in the dog's thigh by anastomosing the graft's blood vessels to the femoral artery and vein. The duct was sutured to an artificial orifice cut in the thigh's skin, from which the saliva was collected. Salivary secretion was induced by a single intravenous bolus of pilocarpine (5 mg). Preoperative (normal) salivation was measured by collecting saliva from the gland in situ. Periodic functional studies showed normal saliva production during the first month after grafting, after which the salivary flow was reduced by 35% over the next 2 months. This reduction was interpreted as a sign of disuse atrophy resulting from the lack of autonomic innervation. To overcome this impediment, oral pilocarpine (5 mg/day) was administered to the recipient dog, after which normal levels of saliva were excreted through the graft during the 3-month follow-up period. The quality of the graft saliva was assessed by its protein and electrolyte levels, which showed close to normal values.

Animals↗

Study of the complex between the contrast agent Iobitridol (Xenetix) and Elastase (PPE): a model for hydrophobic site protection in drug-protein interactions.

PURPOSE: The concept of Hydrophilic Sphere Stabilization, or Hydrophobic Shielding, has been postulated in the synthesis of biocompatible contrast agents in vascular imaging. To improve the safety of these polyiodinated agents, interactions with protein hydrophobic sites in biomacromolecules should be kept as low as possible. In order to evaluate the level of interactions with proteins, we have selected the serine proteinase Elastase, in presence of Iobitridol (Xenetix), as a model. METHODS: The complex between Iobitridol and Pancreatic Porcine Elastase was investigated by X-ray diffraction techniques, on saturated monocrystals, using the synchrotron radiation at 0.98A. RESULTS: In contrast to Iohexol, which displays several interactions including one in the active site, Iobitridol is unable to interact directly with elastase. Only one partially occupied site is found in between two molecules of the crystal packing. CONCLUSIONS: The validation of the "hydrophobic shielding" concept, which was at the origin of the design of the Iobitridol molecule, has been proven to be an essential feature in minimizing in vivo protein interactions.

Animals↗

Chest wall deformity following maximal tissue expansion for breast reconstruction.

Forty-three women, in a series of 150, participated in a prospective study that examined their chest walls for deformities 3 months after maximal tissue expansion for single-breast reconstruction. Computed tomography imaging was used for this purpose. Twenty-one patients underwent immediate breast reconstruction and the other 22 patients underwent delayed reconstruction. Fifty-three percent had some chest wall abnormality. In the delayed group, chest wall deformities were more statistically significant (p < 0.001). Our findings suggest that chest wall deformity is a common occurrence after maximal tissue expansion for breast reconstruction.

Adult↗

Report of the Eriksholm Workshop on auditory deprivation and acclimatization.

The terminology used in studies documenting changes in auditory performance following fitting of hearing aids has been diverse. Definitions for the auditory deprivation effect and auditory acclimatization are offered as a first step in rationalization. Two statements summarize current knowledge concerning auditory deprivation effects and auditory acclimatization, as well as considering the potential implications for research, field trial and clinical practice applications. Potential areas for future research are identified.

Auditory Perception↗

Angiography contrast agents interact with serine proteinases. The molecular structure of the model system elastase/iohexol.

Pancreatic elastase was co-crystallised with iohexol, a tri-iodo benzenic contrast agent used in angiography analyses. The X-ray analysis of the complex reveals the presence of three molecules of iohexol associated with the proteinase with low occupancy factors. Two iohexol molecules are located in and near the active site of the enzyme and provide a model for explaining the inhibition of the hemostatic system, one of the major and inconvenient side effect associated with these chemicals.

Binding Sites↗

Cardiac tamponade as the initial manifestation of primary pericardial mesothelioma.

Although cardiac tamponade is a known complication of malignancy, it is rarely the initial manifestation. We report a 46-year-old male who presented with malignant cardiac tamponade 6 months prior to the definitive diagnosis of primary pericardial mesothelioma. A thorough literature search has not revealed a similar care.

Cardiac Tamponade↗

Rare sites of melanoma: melanoma of the external ear.

A small series of melanomas of the external ear is presented. The presentation in general was late and they varied from 2.6 mm to 4.8 mm in thickness. The outcome in most of the patients (9 patients) was bad and within 3 years only 4 survived. The fact that 9 patients remembered having a nevus that suddenly changed to melanoma emphasizes the need for early removal of such nevi.

Aged↗

Efficacy of the topical anesthetic cream, EMLA, in alleviating both needle insertion and injection pain.

To assess the efficacy of the topical anesthetic cream, EMLA, in alleviating the pain produced by infiltration of local anesthetic prior to surgical skin biopsies, a randomized, double-blind, placebo-controlled study was performed on 54 patients undergoing 162 excisional biopsies. Both pain induced by needle insertion and pain induced by local injection were significantly diminished after topical application of EMLA cream. However, part of the effect was placebo, because the placebo ointment (Vaseline) also produced significant pain alleviation.

Adult↗