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Biomedical subjects

W Wells

Publications and source records attributed to W Wells.

At least 37 records · Page 2Linked to original sources

The combination of in situ hybridization and immunohistochemical analysis: an evaluation of Her2/neu expression in paraffin-embedded breast carcinomas and adjacent normal-appearing breast epithelium.

The combination of in situ hybridization and immunohistochemical techniques can successfully identify viral DNA/RNA in specific subsets of cellular populations. We recently modified this method to evaluate amplification of the oncogene Her2/neu and overexpression of its protein c-erbB-2 in a series of 15 breast carcinomas. This combination allows the simultaneous evaluation of the oncogene and its corresponding protein expression in single cells and specific cellular populations in histologic tissue sections. Double staining demonstrated heterogeneity within breast carcinomas. In addition, both nuclear and cytoplasmic signals were often detected in morphologically normal-appearing adjacent breast epithelium. The ability to view both the oncogene and its corresponding protein in single cells offers a unique look at the biology of c-erbB-2.

Breast↗

Cervical thymic cyst: case reports and review of the literature.

Due to its rarity, cervical thymic cyst is seldom included in the differential diagnosis of a neck mass. Approximately 80 cases have been reported thus far, and most of these cases have occurred asymptomatically in children and adults. Only 5 cases have involved patients younger than 1 year of age. The authors report four new patients with thymic cyst in the neck. Two of the patients were newborns in whom the cyst caused airway obstruction and dysphagia. All four patients underwent successful resection of the lesions, with complete resolution of symptoms. The embryology, histopathology, and differential diagnosis of cervical thymic cysts are also reviewed. The authors recommend that despite its infrequent occurrence cervical thymic cyst should be considered in the evaluation of neck masses in children.

Child, Preschool↗

Clinical trials of bispecific antibody MDX-210 in women with advanced breast or ovarian cancer that overexpresses HER-2/neu.

MDX-210 is a bispecific antibody (BsAb) that recognizes Fc gamma R1 on monocytes and macrophages and the cell surface product of the HER-2/neu oncogene, which is overexpressed on some breast and ovarian cancers. Clinical trials have demonstrated that treatment with MDX-210 is well tolerated and that MDX-210 is both immunologically and clinically active. Optimization of the dose and schedule of MDX-210 and development of combination treatments with cytokines that modulate immune effector cells will greatly enhance the efficacy of this novel BsAb construct for treatment of tumours that overexpress HER-2/neu. We envision that MDX-210 will be effective for treating patients with tumors that overexpress HER-2/neu, especially in the minimal disease setting.

Antibodies, Anti-Idiotypic↗

Video registration virtual reality for nonlinkage stereotactic surgery.

We have combined three-dimensional (3D) computer-reconstructed neuroimages with a novel video registration technique for virtual reality-based, image-guided surgery of the brain and spine. This technique allows the surgeon to localize cerebral and spinal lesions by superimposing a 3D-reconstructed MR or CT scan on a live video image of the patient. Once the patient's scan has been segmented into the relevant components (e.g., tumor, edema, ventricles, arteries, brain and skin), the surgeon studies the 3D anatomy to determine the optimal surgical approach. The proposed intraoperative surgeon's perspective is displayed in the operating room at the time of surgery using a portable workstation. The patient is then brought to the operating room and positioned according to the planned approach. A video camera is trained on the patient from the proposed intraoperative surgeon's perspective. A video mixer merges the images from the video camera and the 3D computer reconstruction. This video mixer can vary the output intensity of the two input images between 100% of either and 50% of both. This visually superimposes the two images, not unlike a photographic double exposure. The patient's position and the 3D reconstruction are then adjusted until the images on the video mixer's output monitor are identical in terms of scale, position and rotation. This superimposition is facilitated by aligning various surface landmarks such as the external auditory canal, lateral canthus, and nasion. In some cases, such as with spinal tumors, capsules placed on the skin prior to scanning serve as fiducials.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Lentigo maligna of the head and neck. Results of treatment by radiotherapy.

BACKGROUND AND DESIGN: Although surgical excision is considered the treatment of choice for lentigo maligna, some elderly patients presenting with large lesions in the head and neck region may not be suitable candidates for surgical management. Radiotherapy has been used for this tumor at the Princess Margaret Hospital, Toronto, Ontario, for over the past 20 years with encouraging results. Fifty-four patients treated between 1968 and 1988 were identified, and their records were reviewed to determine treatment outcome. RESULTS: Younger patients with smaller lesions were treated with surgical excision (n = 18) and achieved an actuarial tumor control rate of 94% at 3 years. Older patients with larger lesions located in the head and neck area were treated by radiotherapy (n = 36), with an actuarial tumor control rate of 86% at 5 years. Three of the four patients not achieving tumor control by radiation were successfully treated with surgical excision, and two of them proved to have malignant melanomas (both Clark's level II) when examined histologically. One patient with residual pigmentation 4 months after treatment was unavailable for follow-up. No patients developed metastatic melanoma. The late cosmetic appearance was acceptable in the majority of irradiated patients, with 11% showing poor cosmesis due to progressive skin pallor, atrophy, and telangiectasia in the treated area. CONCLUSION: Conventional fractionated radiation therapy with superficial x-rays is a simple and effective method of management for lentigo maligna of the head and neck region. It is an excellent alternative treatment to surgical excision, with low morbidity and acceptable long-term cosmetic results.

Adult↗

Chest-wall reconstruction for spondylocostal dysostosis.

A child with respiratory insufficiency due to a lethal syndrome known as spondylocostal dysostosis is described. Severe chest-wall deformities with resultant paradoxical chest-wall motion were successfully corrected by surgical reconstruction of the right thorax. We conclude that patients with the severe lethal form of the syndrome may benefit from aggressive surgical correction of the thoracic abnormality.

Abnormalities, Multiple↗

Right ventricular growth potential in neonates with pulmonary atresia and intact ventricular septum.

The cardiac catheterization data and angiograms of 30 infants with pulmonary atresia and intact ventricular septum were reviewed to evaluate the growth potential of the right ventricle after transventricular pulmonary valvotomy. An index of right ventricular size based upon the tricuspid valve anulus, right ventricular inlet, and right ventricular outlet dimensions was used. Fourteen infants (Group I) were treated with systemic-pulmonary arterial shunts only, whereas 16 infants (Group II) underwent pulmonary valvotomy and 14 had shunting as well. Follow-up studies demonstrated the lack of right ventricular growth in Group I (right ventricular index of 7.0 +/- 3.2 preoperatively versus 7.0 +/- 2.0 postoperatively) and persistence of severe right ventricular hypertension (systolic pressure of 121 +/- 31 versus 120 +/- 48 mm Hg). In contrast, the right ventricular cavity increased in nine of 11 Group II infants who underwent valvotomy. Right ventricular index increased from 7.7 +/- 1.6 to 11.0 +/- 3.1 (p less than 0.01) and systolic pressure fell from 132 +/- 31 to 83 +/- 50 mm Hg (p less than 0.1). Early and late mortality in Group I was 50% (7/14), whereas only three of 16 Group II infants died (p greater than 0.1). It is concluded that pulmonary valvotomy should be attempted in all neonates with pulmonary atresia and intact ventricular septum in whom an outflow tract is identified angiographically to maximize the potential for right ventricular growth and increase its functional contribution to normal circulation.

Blood Circulation↗

Vitamin B12 injections: considerable source of work for the district nurse.

Between June and September 1984, district nurses who worked in Coventry were asked to submit returns giving details of the patients for whom they administered vitamin B12 injections. Of 492 patients identified, 382 (78%) were receiving injections more frequently than the recommended three monthly dose of hydroxy-cobalamin. An extra 3751 injections are being administered a year. Four hundred and thirty (88%) of these patients have conditions for which the drug is of proven benefit, so the increased frequency of injections accounts for most of the observed excess. A total of 2000 hours a year of district nurse time is spent with these patients. The nursing service is under increasing strain. Changes in vitamin B12 prescribing alone could make between 600 and 1470 hours available for other patient needs.

Anemia, Pernicious↗

Rat renal peritubular transport and metabolism of plasma [35S]glutathione.

More than 80% of the plasma glutathione is extracted during a single pass through the kidney. The peritubular component of this extraction was characterized by in situ arterial infusion of [35S]glutathione and [3H]inulin. The peak of 35S-labeled material recovered in the renal venous effluent was delayed approximately 10 S compared with the peak of [3H]inulin. As a result, the initial fractions exhibited a decreased 35S/3H ratio, indicating that 35S-labeled material is transported out of the postglomerular peritubular capillaries. Later fractions exhibited a normalized 35S/3H ratio greater than 1, consistent with the subsequent addition of a 35S-labeled metabolite to the venous circulation. An identical profile was observed when perfusion experiments were repeated using gamma-[35S]glutamyl-S-methylcysteine and [3H]inulin. Renal venous plasma samples obtained from a rat perfused with [35S]glutathione were reduced with sodium borohydride, reacted with monobromobimane, and analyzed by high-pressure liquid chromatography. More than 70% of the recovered 35S-labeled material was identified as cysteine and 20% was recovered as unmetabolized glutathione. Pretreatment of rats with a single injection of AT-125 resulted in 96% inactivation of renal gamma-glutamyltranspeptidase. Under these conditions, the percent of glutathione converted to cysteine (35%) was significantly less than the observed level of renal extraction (61%). Two injections of AT-125 caused a complete inhibition of cysteine formation. However, the residual level of renal extraction (41%) was still significantly greater than the filtration fraction (26%). The peritubular transport of glutathione is stimulated by prior depletion of renal glutathione with buthionine-L-sulfoximine and is competitively inhibited by simultaneous infusion of gamma-glutamylcysteine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Production of pharmacologic monodisperse aerosols.

Monodisperse aerosols containing a range of chemical material, including pharmacologically active substances, were produced by using a modified Sinclair-LaMer condensation generator. Instead of the usual hot-wire technique, an ultrasonic nebulizer was used to suspend nuclei in the gas phase as an aqueous polydisperse aerosol. This technique allowed the generation of monodisperse oil (sebacate) aerosols containing nuclei of sodium chloride, histamine, methacholine, antigen, iron oxide, methylene blue, uranine, radioactive technetium pertechnetate, and technetium-labeled human serum albumin. Quantitative agonist activity was demonstrated for each active nucleus. Particle sizes ranged from 0.65 to 3 microns, with a geometric standard deviation of 1.1-1.2. This system can produce a stable, monodisperse, biologically active radiolabeled aerosol for a period of several hours.

Aerosols↗

Evaluation and surgical treatment of pulmonary atresia and intact ventricular septum in infancy.

The initial surgical approach to the infant with pulmonary atresia and intact ventricular (PA-IVS) is to establish an adequate source of pulmonary blood flow and, when possible, relieve right ventricular (RV) outflow obstruction. The selection of patients for pulmonary valvotomy, alone or in combination with a systemic-pulmonary arterial shunt, depends on the presence of an RV outflow tract and the adequacy of the RV chamber. To evaluate the size of the RV cavity in PA-IVS, an RV index (RVI) was developed using biplane angiographic measurements of the sum of the tricuspid valve annulus and the RV inflow and the RV outflow tracts. The RVI was normalized by relating it to the aortic diameter (Ao) at the diaphragm (RVI/Ao). The RVI/Ao was 13.5 +/- 1.4 in 20 control subjects and only 7.3 +/- 2.6 in 26 PA-IVS patients (p less than 0.001), and was within the normal range in only two of the 26. Since 1976, pulmonary valvotomy plus a Blalock-Taussig shunt has been performed in 10 infants, with one death. Serial cardiac catheterizations in five of nine survivors demonstrated substantial RV growth in all, with the RVI/Ao increasing from an average of 8.0 to 12.5. In contrast, patients who underwent a shunt alone had no change in RV cavity size. We conclude that pulmonary valvotomy may be performed successfully in most PA-IVS patients, but usually must be combined with a systemic-pulmonary shunt. In a small minority of patients, a normal RV cavity, as evidenced by an RVI/Ao greater than or equal to 11, appears to be sufficient to sustain adequate pulmonary blood flow after valvotomy alone. The RVI/Ao ratio is a simple method of quantitatively evaluating RV cavity size and is helpful in planning the initial surgical approach for these infants.

Cardiac Catheterization↗