Biomedical subjects

K D Newman

Publications and source records attributed to K D Newman.

At least 37 records · Page 2Linked to original sources

PubMed1995

Experience with abdominal wall closure for patients with congenital diaphragmatic hernia repaired on ECMO.

Congenital diaphragmatic hernia (CDH) and its attendant lack of abdominal domain can create major technical challenges with respect to diaphragmatic and abdominal wall reconstruction, especially in seriously ill infants who require extracorporeal membrane oxygenation (ECMO). The authors reviewed the medical records of all infants with CDH repaired on ECMO at their institution (group 1, 15 patients), and compared them with infants having CDH repair before ECMO (group 2, 20 patients) and with those who had CDH repair but did not require ECMO (group 3, 15 patients). Thirty-seven of 50 patients survived (74%): 10 in group 1, 12 in group 2, and all 15 in group 3. There was a statistically significant difference (P < .001) with respect to the requirement of a polytetrafluoroethylene (PTFE) diaphragmatic patch for patients in group 1 versus those in both groups 2 and 3. There was also a significant difference in the number of patients in whom the abdomen could not be closed (P < .001 for group 1 v groups 2 and 3). Infants who require ECMO before CDH repair are more likely to have large diaphragmatic defects that require prosthetic reconstruction, and abdominal wall closure problems resulting from loss of abdominal domain, which further complicate the management of the physiological derangements from pulmonary hypoplasia and persistent pulmonary hypertension.

Abdominal Muscles↗

PubMed1995

In vivo adenovirus-mediated gene transfer via the pulmonary artery of rats.

Gene transfer into the pulmonary vasculature has the potential to be a powerful technique for both investigation of pulmonary pathophysiology and development of genetic therapies for pulmonary vascular disease. To evaluate the potential for in vivo pulmonary arterial gene transfer, we infused adenoviral vectors into the left pulmonary artery of Sprague-Dawley and cotton rats. Access to the left pulmonary artery was obtained by a percutaneous transcatheter approach or through thoracotomy and pulmonary arteriotomy. With the thoracotomy approach, both pulmonary arterial inflow and pulmonary venous outflow were occluded during vector influsion and throughout a subsequent 20-minute dwell period. The success of gene transfer was assessed by staining for evidence of recombinant gene expression in lungs excised at time points ranging from 48 to 72 hours after virus infusion. With the thoracotomy technique, pulmonary gene transfer was successful in 15% of surviving Sprague-Dawley rats and 30% of surviving cotton rats. Percutaneous catheter-based pulmonary gene transfer was not successful. In rats with pulmonary gene transfer, 1% to 8% of total left lung cells expressed the recombinant gene. Recombinant gene expression was found in endothelial cells (0.2% to 18% of total transduced cells), smooth muscle cells (0% to 3%), macrophages (1% to 7%), airway epithelial cells (2% to 50%), and alveolar epithelial cells (38% to 94%). Investigation of the low rate of successful gene transfer in individual animals suggested that insufficient physical contact between the virions and pulmonary cells was the most likely cause. In vivo gene transfer into the rat pulmonary vasculature can be accomplished with adenovirus vectors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoviridae↗

PubMed1995

Endothelium-specific in vivo gene transfer.

Targeted expression of genetic material within the vascular endothelium is potentially a powerful tool for the investigation of endothelial cell (EC) biology. We developed, optimized, and characterized an efficient somatic transgenic model of EC-specific gene transfer. Rat carotid arteries were infused with adenovirus expressing a beta-galactosidase (beta-gal) gene. The level and cell-type specificity of recombinant gene expression were measured by assaying beta-gal activity in vessel extracts and by counting transduced cells in histological sections. Toxicity was evaluated by counting total ECs (3 days) and by measuring neointimal formation (14 days). Effects of transduction on the proliferation of vascular cells were measured with bromodeoxyuridine and [3H]thymidine. Maximum recombinant gene expression resulted from infusion of 1 x 10(10) to 1 x 10(11) plaque-forming units (pfu) per milliliter; approximately 35% of luminal ECs were transduced. A high degree of EC specificity (90% to 98% of total transduced cells) was maintained over this range of virus concentrations. More highly concentrated virus resulted in loss of beta-gal expression and a large decrease in luminal EC number (97% decrease, P < .001). Gene transfer at 4 x 10(10) pfu/mL was efficient, preserved EC integrity, and caused minimal neointimal formation. After gene transfer, there were early (3-day) increases in both EC and smooth muscle cell proliferation. At 14 days, only EC proliferation remained elevated (18% versus 1.4% in vehicle-infused arteries, P = .005). This animal model permits efficient highly EC-specific gene transfer. Vascular toxicity is minimal, although the EC proliferative index is elevated. This model will be useful in experiments that elucidate the biological role of EC gene products and define pathways of EC gene regulation and signal transduction in vivo.

Adenoviridae↗

PubMed1995

Adenovirus-mediated gene transfer into normal rabbit arteries results in prolonged vascular cell activation, inflammation, and neointimal hyperplasia.

Adenovirus vectors are capable of high efficiency in vivo arterial gene transfer, and are currently in use as therapeutic agents in animal models of vascular disease. However, despite substantial data on the ability of viruses to cause vascular inflammation and proliferation, and the presence in current adenovirus vectors of viral open reading frames that are translated in vivo, no study has examined the effect of adenovirus vectors alone on the arterial phenotype. In a rabbit model of gene transfer into a normal artery, we examined potential vascular cell activation, inflammation, and neointimal proliferation resulting from exposure to replication-defective adenovirus. Exposure of normal arteries to adenovirus vectors resulted in: (a) pronounced infiltration of T cells throughout the artery wall; (b) upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in arterial smooth muscle cells; (c) neointimal hyperplasia. These findings were present both 10 and 30 d after gene transfer, with no evidence of a decline in severity over time. Adenovirus vectors have pleiotropic effects on the arterial wall and cause significant pathology. Interpretation of experimental protocols that use adenovirus vectors to address either biological or therapeutic issues should take these observations into account. These observations should also prompt the design of more inert gene transfer vectors.

Adenoviridae↗

PubMed1994

Rhabdomyosarcoma of the clitoris.

Genitourinary rhabdomyosarcoma in females usually originates in the vagina or uterus, but rarely the vulva. The authors present a case of rhabdomyosarcoma originating in the clitoris. A 4-year-old with an alveolar rhabdomyosarcoma of the clitoris was treated with radical clitorectomy, radiation, and chemotherapy. Follow-up at 3 years showed no active disease.

Child, Preschool↗

PubMed1994

Optimization of recombinant t-PA secretion from seeded vascular grafts.

Seeding of vascular grafts with genetically engineered endothelial cells (EC) secreting anticoagulant or fibrinolytic agents offers a potential means of improving patency rates. Prior to the initiation of in vivo studies, we examined cell retention and tissue plasminogen activator (t-PA) secretion from small-diameter synthetic graft segments seeded with sheep venous EC genetically engineered to secrete human t-PA. Following retroviral-mediated gene transfer, EC were seeded at varying densities onto 4-mm-diameter synthetic graft segments of different composition, achieving confluent coverage of all materials. t-PA production from seeded grafts was evaluated under both static conditions and after flow exposure, for up to 3 days after seeding. t-PA secretion varied directly with increasing seeding density for all graft types, reaching a maximum of 20 ng/cm2/24 hr. t-PA secretion correlated highly with the number of seeded cells as determined by measurement of DNA from lysates of seeded grafts (r2 = 0.90, P < 0.0001). For all graft types tested, approximately 50% of seeded cells were retained after exposure to flow in vitro. Retained EC remained viable as determined by t-PA secretion. The rate of t-PA secretion from collagen-impregnated Dacron grafts was higher than that obtained with other materials both under static conditions and after flow exposure. This higher rate was most likely due to the higher surface area presented by the Dacron grafts. These data demonstrate that small-diameter prosthetic graft materials can be coated with a layer of EC that (i) remains metabolically active and capable of secreting a fibrinolytic agent, and (ii) remains adherent to the graft surface after exposure to flow. These experiments provide a foundation for in vivo studies in which grafts are seeded with EC genetically engineered to increase local fibrinolysis.

Animals↗

PubMed1994

Diamond flap anoplasty in infants and children with an intractable anal stricture.

After posterior sagittal anorectoplasty for imperforate anus a prolonged course of anal dilatations is necessary until the scar softens. Although rare, severe stricture after this procedure is difficult to resolve. Y-V plasty is not entirely satisfactory because the pedicle advanced into the anus has some tension, which tends to retract producing recurrent stricture. The authors performed a diamond-shaped island anoplasty in eight children with postoperative and strictures (one after an unsuccessful Y-V plasty), with prompt resolution of the stricture in five. The island flap anoplasty consists of a diamond-shaped flap of skin formed laterally, with complete separation of skin and subcutaneous attachments around the periphery of the flap. The skin island is supplied with blood from the deep tissue. An incision is made through the scarred anal ring and into the mucosa, a distance of half the length of the diamond, which is then advanced into the mucosal defect. The defect lateral to the advanced flap is sutured closed. The island of skin descends naturally into the anus, under no tension. The procedure can be performed simultaneously in the 3 o'clock and 9 o'clock positions, and can later be repeated anteriorly and posteriorly, although this has not been necessary. Two of the eight children have required no dilatation postoperatively, a distinct advantage in the 4-year-old patient. One segment in one child sloughed, resulting in repeat stricture that is responding to dilatation. The other seven children are doing well with their colostomies closed.

Anus, Imperforate↗

PubMed1994

Adenoviral vector-mediated gene transfer into sheep arteries using a double-balloon catheter.

The potential for catheter-based in vivo delivery of genetic material to the arterial wall is incompletely explored. We evaluated the level of recombinant protein production as well as the anatomic distribution and duration of gene expression following adenoviral vector-mediated gene transfer into sheep arteries via a double balloon catheter. Catheters were positioned in the carotid or femoral arteries of 20 sheep via a combined percutaneous and surgical approach, and virions infused over a 30-min period. Three days later, recombinant gene expression was identified in approximately 30% (range 0-80%) of the luminal endothelial cells within the targeted area of the artery. Persistent recombinant protein expression was identified histochemically for up to 4 weeks, although the number of positive cells decreased steadily. High levels of both beta-galactosidase (beta-Gal) activity and protein (mean 20 mU and 44 ng per vessel) were measured in vessel extracts 3 days after gene transfer, again decreasing significantly over a 4-week period. Transgene expression was limited almost entirely to the intima and adventitia; adventitial gene transfer occurred virtually exclusively along the vasa vasorum. In comparison to previous studies of catheter-based gene transfer, adenoviral vectors delivered by double balloon catheter resulted in a particularly high efficiency of endothelial cell gene transfer. The efficiency and amount of recombinant gene expression achieved in this study suggest that catheter-based gene delivery may eventually be applicable to the treatment of focal human arterial disease.

Adenoviridae↗

PubMed1994

Insulin measurement and preparation among diabetic patients at a county hospital.

The investigator conducted a pilot study of 52 insulin-using adult diabetic patients at an urban county hospital in the Southeast. The purpose was to assess the ability of adult diabetic patients to measure and prepare insulin in a syringe. Results indicated that patients exhibited important deficits in their ability to prepare and measure insulin in a syringe. In addition, many subjects had difficulty with basic arithmetic involving addition and were unable to calculate their total amount of regular and long-acting (NPH) insulin. Other interesting findings were: 1) 48% did not roll the NPH vial to mix it properly, 2) 71% of the sample population did not eliminate air bubbles from the syringe, and 3) 23% of the sample population contaminated the regular insulin with the NPH insulin. Factors found to be associated with patients' insulin preparation tasks were age, arthritis of the hands, visual acuity, and education.

Adolescent↗

PubMed1994

Anatomic barriers influence the distribution of in vivo gene transfer into the arterial wall. Modeling with microscopic tracer particles and verification with a recombinant adenoviral vector.

We evaluated the extent to which anatomic barriers to vector penetration might influence the distribution of successful in vivo gene transfer into the normal arterial wall. A double-balloon catheter technique with infusion pressures of 100 to 400 mm Hg was used to infuse microscopic tracer particles of the size range of liposomes and viral vectors into normal elastic arteries of sheep. Localization of the tracer particles in tissue sections by light, fluorescence, and electron microscopy suggested that vector-sized particles were delivered to the intima by direct infusion and to the adventitia via the arterial vasa vasorum. Particles were virtually absent from the arterial media. To test the predictions made from the particle studies, we repeated the infusion protocol with high-titer adenoviral vectors. Gene transfer occurred at high levels in the intima and along the adventitial vasa vasorum but again was virtually absent within the media. The ability of medial smooth muscle cells to be transduced was established in separate experiments with a high-pressure (5 atm) porous balloon infusion catheter. We conclude that (1) the anatomy of the normal elastic arterial wall imposes significant limitations on the penetration of particles in the size range of most gene-transfer vectors and (2) the distribution of in vivo gene transfer with adenoviral vectors is correctly predicted by the distribution of inert tracer particles. These findings have important implications for the design of arterial gene-transfer and gene-therapy protocols.

Adenoviridae↗

PubMed1993

Visualization of enlarged mesenteric lymph nodes at US examination. Clinical significance.

PURPOSE: To identify conditions associated with enlarged mesenteric lymph nodes in children with acute abdominal pain and determine the ability of US to detect associated abnormalities. METHODS: Two hundred and fifty children with acute abdominal pain were evaluated for the presence of enlarged mesenteric lymph nodes (AP diameter > 4 mm). Additionally, a reference group of 50 asymptomatic children was also studied for the presence of enlarged mesenteric lymph nodes. RESULTS: Enlarged mesenteric lymph nodes were noted in 35 (14%) symptomatic children and two (4%) asymptomatic children. A specific diagnosis was established in 16/35 (46%) symptomatic children with mesenteric lymphadenopathy. Acute appendicitis was the most common diagnosis. The discharge diagnosis in the remaining 19 children was abdominal pain or gastroenteritis of unknown origin. US suggested the correct diagnosis in 12/16 (75%) children in whom a definite diagnosis was established. Histopathologic examination of enlarged mesenteric lymph nodes in three patients demonstrated non-specific inflammatory changes. CONCLUSION: Enlarged mesenteric lymph nodes in children with acute abdominal pain represents a nonspecific finding. Mesenteric lymphadenopathy is associated with a variety of medical and surgical conditions in symptomatic children and is occasionally seen in asymptomatic children. Sonography is useful in establishing a primary diagnosis in these children.

Abdominal Pain↗

PubMed1993

Protocols for college health nurses: alive and well in the 1990s.

This article seeks to assist college health nurses in developing appropriate protocols for patient care. In addition, the authors outline factors influencing protocol content, design, and development and describe steps in creating individualized protocols by practice setting. To provide college health nurses with a basic understanding of protocols, the authors offer definitions and examples of appropriate and inappropriate use, and show how protocols can influence the delivery of patient care. Although protocols may provide college health nurses with directives for managing specific health problems, they require a sophisticated level of judgment and skill in their implementation.

Female↗

PubMed1993

Giving up: shelter experiences of battered women.

Within the last decade intrafamilial violence has been identified as a major health and social problem. Women in particular are at high risk for battering and often seek refuge in shelters. Empirical evidence is required regarding the experiences of battered women who use these shelters. Therefore, we collected qualitative data from interviews with seven battered women and by observation in ten group counseling sessions at a shelter in the Southeast. Using grounded theory methodology, the core concept that emerged was "giving up." Supporting concepts were helplessness and fear of the unknown. The participants found it easier to give up and return to the abusive relationship than to seek alternatives.

Adaptation, Psychological↗

PubMed1993

The current management of thyroid tumors in childhood.

Thyroid cancer is a rare but intriguing malignancy when it occurs in childhood and adolescence. Although it often presents at a more advanced stage than similar adult thyroid tumors, the biologic behavior is more benign, accounting for improved survival. Therefore, pediatricians and surgeons have debated the wisdom of aggressive versus conservative surgical approaches. Although the final answers have not been achieved it has become increasingly clear that radical surgical approaches may be unnecessary. Further investigation of the tumor cell biology, genetics, and molecular biology of thyroid tumors may allow prospective classification of children so that the best operative and adjuvant management can be selected for each individual.

Child↗

PubMed1992

A community health nursing curriculum and Healthy People 2000.

The School of Nursing at the University of Alabama at Birmingham recently revised its graduate level community health nursing curriculum based on the priority areas and health objectives in Healthy People 2000. Health priority areas are presented as class topics and provide direction for the students' fieldwork. This paper provides background on the national strategy used to develop the national health objectives, suggestions on how nursing can be at the forefront of influencing the health of the nation, and specifics involved in implementing a community health nursing curriculum using the year 2000 health objectives.

Community Health Nursing↗

PubMed1992

Molecular characterization of the soybean alcohol dehydrogenase gene family amplified in vitro by the polymerase chain reaction.

Soybean (Glycine max) alcohol dehydrogenase (ADH) cDNAs were amplified in vitro from total RNA by the polymerase chain reaction (PCR). The amplification strategy involved first strand cDNA synthesis from anaerobic cotyledon total RNA using an 18-thymidine primer. The second strand cDNA primer was a conserved sequence near the 5' end of known plant ADH transcripts. The PCR products were ligated into a plasmid vector and unique clones were isolated on the basis of size and restriction pattern. Sequence analysis revealed three distinct classes of soybean ADH cDNAs, all of which showed high homology to Adh genes from maize and peas. RNA blot hybridization analyses showed differential expression patterns for these genes. One gene, expressed constitutively in all seedling organs, was inducible by anaerobiosis, one gene was expressed only in anaerobic organs, and the third gene was expressed predominantly in anaerobic roots.

Journal Article↗

PubMed1992

Appendicitis: usefulness of US in diagnosis in a pediatric population.

One hundred eighty pediatric patients with suspected appendicitis were prospectively examined with graded compression ultrasonography (US) to assess the sensitivity, specificity, and accuracy of graded compression US in the diagnosis of appendicitis in children and to compare those results with results of clinical assessment in the diagnosis of this disorder. Patients were assigned to one of three groups prior to US based on the clinical level of confidence that appendicitis was present and on the planned management decision. Of 141 patients in the low- and intermediate-clinical risk categories, 20 (14%) had appendicitis: US had a sensitivity of 100%, specificity of 97%, and accuracy of 97% in these two groups. Of 39 patients in the high-clinical risk category, 32 (82%) had appendicitis: US had a sensitivity of 81%, specificity of 86%, and accuracy of 82%. Of 52 patients with surgically proved appendicitis, the initial management decision was to discharge to home or admit for observation and further testing in 18 (35%). Results at US were positive for appendicitis in all 18 patients in the latter two categories.

Adolescent↗

PubMed1992

Low level in vivo gene transfer into the arterial wall through a perforated balloon catheter.

BACKGROUND: Gene transfer into the arterial wall may provide a novel therapeutic strategy for the treatment of coronary artery restenosis. Previously described methods for gene transfer into the arterial wall require total vessel occlusion for 30 minutes. We sought to develop a protocol for gene transfer within a more clinically relevant time frame. METHODS AND RESULTS: We used a perforated balloon (Wolinsky) catheter to inject retroviral vector-containing virions into rabbit aortas in vivo. The virions were injected within 1 minute. Aortas were removed 5-14 days after injection and analyzed for evidence of gene transfer. In initial studies, nine rabbits were injected with a vector expressing the beta-galactosidase gene, and nine rabbits were injected with either non-beta-galactosidase-containing vectors or with a vehicle control. Histochemical staining of aortic tissues revealed blue (positive) cells in eight of nine experimental rabbits and six of nine controls. Because of the lack of specificity of the beta-galactosidase detection system, we adopted a polymerase chain reaction-based protocol in which oligonucleotide primers were used to amplify specific vector-related sequences from aortic tissue extracts. The polymerase chain reaction protocol, calibrated with standards containing known numbers of transduced cells, revealed low amounts of vector-related sequences in six of 12 vector-injected rabbits and in one of 13 controls (p less than 0.03). Comparison with standards indicated that fewer than 100 transduced cells were present in a 2-cm length of the injected aortic tissue. CONCLUSIONS: Although in vivo gene transfer through an infusion balloon catheter can be accomplished within 1 minute, the therapeutic use of this protocol is limited by the small number of cells that are transduced.

Animals↗