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Biomedical subjects

J D Kennedy

Publications and source records attributed to J D Kennedy.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of spinal surgery on lung function in Duchenne muscular dystrophy.

BACKGROUND: The effect on subsequent respiratory function of spinal stabilisation for scoliosis in Duchenne muscular dystrophy is unclear. In order to clarify this clinical problem, changes in the forced vital capacity of a group of children with Duchenne muscular dystrophy who had undergone spinal surgery were measured and compared with a group of children with Duchenne muscular dystrophy who had not had surgery. METHODS: In this retrospective study 17 boys with Duchenne muscular dystrophy who underwent spinal stabilisation at a mean age of 14.9 years (surgical group) were compared with 21 boys with Duchenne muscular dystrophy who had not had surgery (non-surgical group). The mean (SD) Cobb angle of the surgical group at 14.9 years was 57 (16.4) degrees, and of the non-surgical group at 15 years was 45 (29.9) degrees. Forced vital capacity expressed as percentage predicted (% FVC) was measured in total over a seven year period in the surgical group and over 6.5 years in the non-surgical group, and regression equations were calculated. Survival curves for both groups were also constructed. RESULTS: No difference was found between spinal stabilisation (surgical group) and the non-surgical group in the rate of deterioration of % FVC which was 3-5% per year. There was no difference in survival in either group. CONCLUSIONS: Spinal stabilisation in Duchenne muscular dystrophy does not alter the decline in pulmonary function, nor does it improve survival.

Adolescent↗
PubMed1995

Phenotypic characterization of T lymphocytes emigrating into lung tissue and the airway lumen after antigen inhalation in sensitized mice.

Cytokines released from CD4+ T lymphocytes contribute to the pathogenesis of asthma by influencing the differentiation and function of eosinophils, the primary effector cells that cause airway epithelial damage. Using a model of ovalbumin (OA)-induced, eosinophil-rich chronic lung inflammation in sensitized mice, we have defined the role of T lymphocytes further by using three-color flow cytometry to characterize the adhesion and activation antigens that may be associated with the migration of these cells into the lung and airway lumen. OA inhalation in OA-sensitized C57BL/6 mice resulted in an early (6 to 24 h) influx of neutrophils into the bronchial lumen as enumerated by bronchoalveolar lavage (BAL), which was followed by a marked accumulation of lymphocytes and eosinophils between 24 to 72 h. Phenotypic analysis of BAL or lung tissue T cells showed that most Thy-1 CD3+ T cells were CD4+ (CD4: CD8 ratio of 3 to 4:1). The majority (90%) of the T cells in lung or BAL fluid expressed alpha beta T-cell receptors (TCR). Only 3 to 7% of the T cells were gamma delta TCR+ even though almost 25% of the T cells were CD4- CD8-. There were very few natural killer (NK) or B cells in BAL fluid compared with 15% B cells in dissagregated lung tissue. In contrast to T cells in spleen, almost all the lung and BAL T cells were of the memory phenotype, as ascertained by the expression of high levels of CD44 and by the absence of L-selectin and CD45RB on the cell surface. Fifty to ninety percent of lung and BAL T cells from vehicle-sensitized or OA-sensitized and challenged mice expressed the adhesion molecules CD11a (LFA-1), CD54 (ICAM-1), and CD49d (VLA-4). The early T-cell activation marker CD69 was upregulated on 30% of the lung and BAL T cells in OA-sensitized mice after antigen inhalation. When BAL fluid T cells from OA-sensitized and challenged mice were analyzed for their coexpression of adhesion and/or activation molecules, 75% of the cells that expressed one of three adhesion molecules, CD54, CD49d, or CD11a, also expressed at least one of the other two antigens. At least 15% of BAL T cells had all three of these molecules on their cell surfaces. The OA-dependent, temporally regulated emigration of T cells into the bronchial lumen after exposure to aerosolized antigen may be correlated with the accumulation of cells that express the memory phenotype with enhanced expression of adhesion molecules.

Administration, Intranasal↗
PubMed1994

Review of skull base surgery approaches: with special reference to pediatric patients.

The techniques of skull base surgery attempt to maximize the exposure of a cranial base lesion while using the least amount of brain retraction. Cranial base surgery is not a 'new' area of neurosurgical or otolaryngologic interest, but instead represents a resurgence of efforts to treat difficult lesions involving the cranial base. This resurgence of interest and effort is a product of recent advances in microanatomical knowledge of the cranial base, advances in microsurgical technique, improved neurophysiologic monitoring, and improved collaborative relationships between neurosurgery, otolaryngology and plastic surgery. Furthermore, improved neuroanesthetic techniques allow the surgeon to proceed with surgery without undue concern about time, and improved neuroimaging techniques provide the surgeon with detailed knowledge of the three dimensional characteristics of the tumor and surrounding structures. This review will focus on the surgical management of cranial base tumors primarily affecting the pediatric population. Little has been written on the techniques of skull base surgery as they apply to the pediatric population, since cranially-based tumors are a relatively rare occurrence in this patient population. In most instances, however, many of the 'standard' skull base approaches can be applied to the pediatric patient with few modifications, and in our experience, the pediatric patients have tolerated these approaches as well as their adult counterparts.

Adolescent↗
PubMed1994

Fetal lung compliance in premature and term lambs after two methods of in utero repair of diaphragmatic hernia.

BACKGROUND: In utero surgery was used to correct a surgically induced model of congenital diaphragmatic hernia (CDH) in premature and term lambs, resulting in an improvement in lung mechanics at birth. METHODS: The differences between the in utero "patch" repair method and the "silo" repair method were assessed in 55 lambs by measuring the static respiratory system compliance (CST,RS) at birth in term (approximately 145 day) and in premature (128 day) animals. RESULTS: Both methods resulted in similar improvements in CST,RS in term lambs, but in premature lambs only the silo method produced an increase in compliance. Comparisons of specific compliance related to length or birth weight did not alter these findings; however, corrections related to lung weight or a measure of lung volume showed there was no difference between any experimental groups in either term or premature lambs. CONCLUSIONS: These findings suggest that there was no difference in the intrinsic compliance of the lung tissue between normal, unrepaired and repaired animals, and that the differences in respiratory system compliance measured at birth may be due primarily to differences in lung size. The silo repair method appears to provide an earlier improvement in CST,RS than the patch repair method.

Animals↗
PubMed1993

Intrathoracic silo for fetal diaphragmatic hernia: lung growth and slow reduction of abdominal viscera.

Correction of a left congenital diaphragmatic hernia in a human fetus with a large volume of liver in the chest requires reduction of liver and viscera into the abdomen. This can kink the ductus venosus and cause the death of the fetus. Therefore, we have repaired surgically created diaphragmatic hernias in fetal lambs by leaving viscera in the chest wrapped in a silastic chimney. With fetal growth there is a relative reduction of hernia volume over weeks, potentially avoiding kinking the ductus venosus. In four groups of lambs lung size and static respiratory system compliance at birth were compared. Lambs treated by this new technique (silo, n = 7) were compared with lambs that had undergone immediate complete correction with a flat silastic patch in the diaphragm plus an abdominal patch (patch, n = 8), with lambs with uncorrected hernias (n = 6), and with normals (n = 8). There was no significant difference between total lung weights (131 +/- 6 g v 157 +/- 13 g, mean +/- SEM, silo v patch) and lung displacement volumes (142 +/- 7 mL v 162 +/- 14 mL) in either surgically corrected group. Lungs from those corrected by silo were significantly heavier than those with uncorrected herniae (131 +/- 6 g v 56 +/- 5 g, P < .01), but were not as heavy as normal lungs (131 +/- 6 g v 257 +/- 16 g, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Extrathymic T cell maturation. Phenotypic analysis of T cell subsets in nude mice as a function of age.

T cell maturation in an extrathymic environment has been studied using as a model the congenitally athymic nude mouse. Phenotypic analyses as a function of age were conducted on lymphocytes obtained from the spleens and lymph nodes of nude mice through use of mAb recognizing T cell surface markers and multiparameter flow cytometry. The data show that nude mice accumulate increasing numbers of lymphocytes bearing Thy-1, CD3, CD4, and CD8 with age characterized by a progression from heterogeneous dim to more homogeneous bright expression. In contrast, the expression of heat-stable Ag (HSA), a marker of immature thymocytes, decreases with age. By analogy to intrathymic maturation, spleens and lymph nodes in nude mice contain T cells defined as immature, transitional, and mature based on the expression of these markers. Although the proportion of CD4+ and CD8+ T cells associated with bright CD3 expression increases with age, at no age are significant numbers of CD4+8+ cells observed, in contrast to intrathymic T cell maturation. In addition to the frequently observed inversion in the ratio of CD4 to CD8, the CD8 T cell subpopulation in older nude mice contains mainly mature cells (CD8+, CD3+, HSA-) whereas only 50% of CD4+ T cells express the mature (CD4+, CD3+, HSA-) phenotype. At any age, the spectrum of phenotypes observed indicates that lymph nodes contain more mature T cells than spleen, suggesting a role for environmental Ag in driving extrathymic maturation, a process occurring most efficiently among CD8+ T cells. Because extrathymic maturation mirrors some but not all aspects of the intrathymic pathway, we propose that the nude mouse may be a useful model for further dissecting those interactions crucial to establishing the T cell repertoire in euthymic individuals as well as elucidating the contribution of extrathymically derived T cells to the peripheral immune system.

Age Factors↗
PubMed1991

CD8+ alpha/beta or gamma/delta T cell receptor-bearing T cells from athymic nude mice are cytolytically active in vivo.

Phenotypic analysis of lymphocytes that mature extrathymically in congenitally athymic nude mice has revealed a large population of CD3+ CD8+ T cells that express gamma/delta-TCR. In euthymic mice, significant numbers of cells with this phenotype are found only in the intestinal epithelium. Intestinal intraepithelial lymphocytes have been shown to be cytolytically active in vivo, as measured by the redirected lysis assay. In this communication, freshly harvested T cell subsets obtained from pooled nude mouse spleen and lymph nodes and separated by flow cytometric cell sorting were assayed for their ability to lyse FcR+ P815 targets in the presence of mAb to the epsilon-chain of the CD3 complex. CD8+, but not CD4+ or CD4- CD8-, T cells in nude mice were cytolytically active. CD8+ alpha/beta- and gamma/delta-TCR-bearing T cells from the spleen and lymph nodes of nude mice demonstrated similar cytolytic activity. No cytolytic activity of purified cell subsets was apparent in the absence of anti-CD3 mAb, even when NK-susceptible target cells were used. These data indicate that, in contrast to euthymic mice, a large proportion of CD8+ cells from the spleen and lymph nodes of nude mice are cytolytically active in vivo. In addition, these results suggest that the intestinal epithelium is not the only anatomical location where constitutively cytolytic CD8+ alpha/beta- or gamma/delta TCR-bearing T cells may be found.

Animals↗
PubMed1991

T cell receptor expression by T cells that mature extrathymically in nude mice.

The expression of TCR by T cells that mature extrathymically in nude mice was determined by staining Ig- cells from B10 nude mice that were 5 months of age or older with mAbs specific for CD3, alpha/beta or gamma/delta TCR. Although the majority of Ig- cells in older nude mice express TCR, the distribution of alpha/beta and gamma/delta TCR in relation to CD4 and CD8 expression is markedly different compared to T cells from euthymic mice. Approximately half of the CD3+ T cells found in the spleen and lymph nodes of nude mice express gamma/delta TCR that is equally distributed between CD4-8- double-negative and CD8+ single-positive T cells. These data provide the first quantitative measure of the expression of TCR by T cells that mature in the absence of a thymus and suggest that the extrathymic environment, although not efficient, is permissive for the maturation of T cells that express alpha/beta and gamma/delta TCR.

Animals↗
PubMed1990

Intralesional immunotherapy of brain tumors with combined Corynebacterium parvum and recombinant interleukin-2 in mice.

Clinical observations and experimental work suggested that inflammatory cells attracted to the brain exert a nonspecific antineoplastic effect. Intralesional treatment of implanted malignant murine brain tumors (KHT sarcomas) with killed Corynebacterium parvum produced an inflammatory cell infiltrate and increased survival in C3H mice relative to that in untreated control C3H mice. This antitumor effect was enhanced when recombinant interleukin-2 was sequentially added as a second intralesional immunomodifier. A high percentage of mice so treated were cured. Inflammatory cells in the brains of treated mice divided for 1-2 weeks, and metabolic activity of astrocytes increased. These findings form the basis for a recently initiated immunotherapy protocol in patients with recurrent glioblastoma multiforme.

Animals↗
PubMed1990

Pseudo-Bartter's syndrome in cystic fibrosis.

Seven cases of cystic fibrosis complicated by chronic salt depletion and failure to thrive were studied. After replacement of the salt deficit, the metabolic abnormalities resolved, and weight gain was rapid. This should be considered as a differential diagnosis in children who have been diagnosed as having cystic fibrosis, but who fail to thrive despite standard treatment.

Alkalosis↗
PubMed1989

Effect of intracerebrally injected Corynebacterium parvum on implanted brain tumor in mice.

Experiments were performed to determine the effectiveness of Corynebacterium parvum on resistance to growth and development of tumor in the central nervous system. A syngeneic sarcoma was injected intracerebrally into C3H/HeN/MTV-negative female mice that had received intraperitoneal injections of C. parvum or saline prior to tumor inoculation or that received intraperitoneal C. parvum or saline after tumor inoculation. Groups then received an intracerebral injection of C. parvum or saline. Our results reveal that intracerebral C. parvum elicited an intracerebral inflammatory reaction which was enhanced by prior systemic priming with C. parvum. Any inflammatory reaction which was enhanced by prior systemic priming with C. parvum. Any inflammatory reaction produced by C. parvum retarded the growth of intracerebrally-implanted sarcoma and significantly increased the survival of mice bearing such tumors. These results suggest that C. parvum may be an effective therapeutic agent in the treatment of neoplasia of the central nervous system.

Animals↗
PubMed1989

Effect of intracerebrally injected Corynebacterium parvum on the development and growth of metastatic brain tumor in mice.

Using KHT tumor in a mouse metastatic tumor model, we examined the effect of intracerebral and/or intraperitoneal injections of Corynebacterium parvum on the growth of metastatic brain tumor and the development of an inflammatory response in the central nervous system (CNS). C. parvum given intraperitoneally had no effect on the development and growth of CNS tumor, but did prolong the survival of mice by inhibiting the growth of systemic metastatic tumor, which was the cause of death in our tumor model. Mice that received intracerebral injections of C. parvum exhibited significantly decreased growth of metastatic brain tumor, as compared with mice that received intracerebral injections of saline, whether or not they had received C. parvum intraperitoneally. In addition, the brains of mice that received C. parvum intracerebrally exhibited an inflammatory response that was minimal or absent in the brains of control mice. Our results suggest that if immunotherapeutic agents can be delivered to the CNS and cause an inflammatory response, they can be effective against CNS metastases.

Animals↗
PubMed1989

Effect of bracing on respiratory mechanics in mild idiopathic scoliosis.

The use of a corrective orthopaedic brace is an established form of management for patients with progressive idiopathic scoliosis. Thirteen patients with mild idiopathic scoliosis were studied with and without the corrective brace applied. Lung volumes and the pattern of chest wall and abdominal movement were measured during quiet breathing. Transdiaphragmatic pressures were measured in six of the patients and upper ribcage movement in seven patients. Application of the brace resulted in a significant reduction in vital capacity (14%), functional residual capacity (22%), and total lung capacity (12%). There was no effect on respiratory rate or minute volume. In the erect position the pattern of chest wall movement was altered with a reduction in lower ribcage movement of 46% and abdominal wall of 39% and an increase in upper ribcage movement of 43%. These changes were greater in the supine position. There was at least a twofold increase in end inspiratory and end expiratory gastric pressures during tidal breathing, but oesophageal pressures were not affected by the brace. Transdiaphragmatic pressures showed a similar twofold increase, which implies a substantial increase in the work of breathing. In view of the doubts concerning the influence of bracing on the natural history of idiopathic scoliosis and the substantial functional effect of bracing on the respiratory system, it is suggested that the current practice of bracing in this condition needs to be reviewed.

Adolescent↗
PubMed1987

Brain stem glioma presenting as gastro-oesophageal reflux.

Brain stem gliomas may present as gastro-oesophageal reflux. In such cases gastro-oesophageal reflux presents atypically late, and computed tomography may not detect the presence of the tumour until late in the course of the disease.

Brain Neoplasms↗
PubMed1987

Pulmonary restrictive effect of bracing in mild idiopathic scoliosis.

The use of bracing in the treatment of mild idiopathic scoliosis is controversial. A study of 33 adolescents showed that bracing significantly decreased lung volumes. Functional residual capacity was reduced by a mean of 26%, 18% of children showing a reduction of greater than 40%. The mean reduction in total lung capacity was 16% and in forced vital capacity 18%. This restriction of lung function by bracing might have a deleterious effect on lung growth or might impose an additional risk factor in the presence of other disorders, such as asthma and diaphragmatic weakness. The use of bracing in individuals with mild scoliosis should be judiciously reassessed.

Adolescent↗
PubMed1986

Value of chest ultrasonography versus decubitus roentgenography for thoracentesis.

Chest ultrasonography (CU) has been advocated as an effective tool for diagnosis and localization of pleural fluid. Studies to date supporting the technique have been anecdotal and nonrandomized. To determine if CU was beneficial when thoracentesis was performed by clinicians or house staff, we evaluated prospectively 205 patients presenting with pleural effusion at 2 community teaching hospitals. Decubitus roentgenograms were obtained on all patients, but CU with targeting by skin marker was performed on a randomized basis. Results were evaluated as to (1) whether the quantity of fluid obtained was sufficient for the intent of the procedure, (2) the number of needle insertions required to obtain the fluid, and (3) the incidence of complications such as pneumothorax. One hundred three effusions were evaluated by CU and 102 by roentgenography alone. The effusions in each group were stratified as small (obliteration of less than half of the hemidiaphragm on roentgenogram) or large. Small effusions were further stratified as free flowing or loculated (no layering of fluid on decubitus roentgenograms). By chi-square test, CU was significantly superior to decubitus roentgenograms alone for obtaining adequate fluid samples in small effusions (p less than 0.01). This was true regardless of whether the effusion was loculated (p less than 0.02) or free flowing (p less than 0.05). The technique had no such advantage in large effusions. We did not find that CU significantly reduced the need for multiple attempts nor incidence of complications in any group.

Drainage↗