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Biomedical subjects

M A Kelly

Publications and source records attributed to M A Kelly.

At least 19 recordsLinked to original sources
PubMed1992

Birth weight threshold for postponing preterm birth.

OBJECTIVE: The study was designed to determine the birth weight threshold at which obstetric efforts intended to delay delivery might potentially improve rates of neonatal morbidity and mortality among pregnancies delivered after spontaneous preterm labor or rupture of the membranes. STUDY DESIGN: We studied 1147 singleton infants with birth weights between 1000 and 2499 gm and whose only complication was spontaneous preterm labor or preterm rupture of the membranes. The Mantel-Haenszel chi 2 statistic was used to evaluate trends for neonatal mortality and several indexes of morbidity. RESULTS: The birth weight threshold for neonatal mortality was 1600 gm (p < 0.001). For neonatal morbidity the threshold was between 1600 and 1900 gm (p < 0.008). CONCLUSION: Aggressive obstetric attempts to prevent preterm birth for infants whose weights exceed 1900 gm offers few apparent potential benefits.

Birth Weight↗
PubMed1992

The role of drugs in the etiology of stroke.

Drugs of many classes have been implicated in hemorrhagic and ischemic stroke. Alcohol in moderation may have a protective effect although in greater doses may predispose to stroke. Drugs such as cocaine, amphetamines and heroin have been associated with stroke by a number of mechanisms. Antiplatelet, anticoagulant and thrombolytic therapy carry risk of hemorrhagic complications. Oral contraceptives appear to slightly increase stroke risk whereas estrogen replacement therapy may decrease it. Anabolic steroid use in athletes has been linked to stroke. The antineoplastic agent L-asparaginase has been associated with cerebral hemorrhage, ischemic infarction and venous sinus thrombosis. Infarction has been reported in association with cisplatin-based combination chemotherapy. Stroke is an infrequent but recognized complication of some forms of drug therapy and drug abuse.

Animals↗
PubMed1992

Rhinocerebral and nasal zygomycosis in sheep caused by Conidiobolus incongruus.

The clinical findings, pathology and mycology of a cluster of 5 ovine cases of rhinocerebral and nasal zygomycosis caused by Conidiobolus incongruus are described. All cases were in Border Leicester or Merino x Border Leicester ewes from a flock pastured in a low-lying paddock adjoining a small tidal river in subtropical Queensland (latitude 28 degrees S). These cases of zygomycosis are believed to be the first infections due to C incongruus recorded in animals other than humans. The disease was subacute in 4 animals with a course of up to several weeks. In these, the primary site of infection was the posterior nasal cavity. The lesions extended to the dorsum of the face between the eyes, to the orbital cavity and to the anterior brain and meninges in the cranial cavity. In one animal, where the anterior nasal cavity was affected and iodine treatment used, the course was longer. The fungal granulomas had numerous foreign body giant cells, neutrophils and eosinophils. Fungal hyphae were thin walled, 6 to 8 microns in diameter, with occasional septa and irregular branching. They were cuffed with a wide zone of necrotic cell coagulum, or with homogeneous eosinophilic Splendore-Hoeppli granules.

Animals↗
PubMed1992

Historical perspectives of chondromalacia patellae.

Widespread misuse of the term chondromalacia has led to confusion regarding its true meaning. This term should not be used to diagnose patellofemoral pain, but to describe lesions of articular cartilage. Recent advances using stereophotogrammetry to evaluate the patellofemoral joint and its articular cartilage may lead to new insight into the etiology of these lesions.

Cartilage Diseases↗
PubMed1992

Patellectomy.

We believe the patella should be preserved when possible and stress the significant use the patella has in normal knee function. Although alternative treatments can often be found, patellectomy may be indicated in selected patients to improve function and reduce pain.

Humans↗
PubMed1991

MR imaging of the knee: clarification of its role.

In an attempt to further delineate the role of magnetic resonance (MR) imaging in evaluating knee pathology, a retrospective study of 60 patients who underwent MR scanning before arthroscopy was undertaken. For medial meniscus tears, the sensitivity of MR imaging was 97% whereas its specificity was 77%. For lateral meniscus tears, MR imaging was 90% sensitive and 87% specific. The positive predictive value of MR imaging was 85% for medial meniscus tears and only 79% for lateral meniscus tears. The negative predictive value was 95% for the medial meniscus and 94% for the lateral meniscus. MR imaging had an accuracy of 93% in assessing anterior cruciate ligament pathology also. These results begin to clarify the role of MR imaging in evaluating intraarticular knee pathology. Grade III signals represented tears at arthroscopy more than 90% of the time. False-positive results occurred more frequently than false negative results did. The high negative predictive value of MR imaging indicates that with a negative MR image, the orthopaedist can reliably conclude that no meniscal pathology is present. MR imaging is a useful diagnostic tool; however, it should be used selectively and in conjunction with the clinical examination in evaluating internal derangements of the knee.

Adult↗
PubMed1991

Use of costal cartilage cantilever grafts in negroid rhinoplasties.

Dorsal augmentation and nasal tip refinement are important objectives in Negroid rhinoplasty. Use of a costal cartilage cantilever graft will achieve these objectives. We report on our experience in 19 patients. The technique offers an excellent solution to supplying the large amount of material often required to adequately augment the dorsum in these patients. The graft is also versatile enough to allow nasal tip refinement. There are additional aesthetic benefits as the cantilever causes a lengthening in the nasal columella, a reduction in the flare of the nostrils, and increases the columellar-labial angle. The procedure is relatively simple to perform. The problem of warping is minimized by symmetrical carving and the use of large grafts with a substantial cross-section.

Anthropometry↗
PubMed1990

Observations on the cause of oligohydramnios in prolonged pregnancy.

There is increasing evidence that implicates reduced amnionic fluid volume as a major determinant of fetal risk in prolonged pregnancy. We sought to determine whether reduced fetal urine production might be associated with oligohydramnios in pregnancies that reach 42 weeks or more. Ultrasonographic measurements of the fetal bladder were obtained every 2 to 5 minutes for 1 hour in 38 gestations verified to be at least 42 weeks. Oligohydramnios was present in eight of the prolonged pregnancies. Similar measurements were performed in 15 normal pregnancies delivered by elective repeat cesarean section between 38 and 40 weeks' gestation. Hourly fetal urine production rates were calculated with sequential bladder volume measurements. The result of this investigation suggest that diminished fetal urine production is associated with oligohydramnios in prolonged pregnancy. The mechanism by which fetal urine production is reduced in prolonged pregnancy remains unknown. A likely possibility is reduced fetal swallowing because of already diminished amnionic fluid volume, the latter a result of placental senescence.

Chi-Square Distribution↗
PubMed1990

Material properties and structure-function relationships in the menisci.

The menisci serve several important biomechanical functions in the knee. They distribute stresses over a broad area of articular cartilage, absorb shocks during dynamic loading, and probably assist in joint lubrication. These functions enhance the ability of articular cartilage to provide a smooth, near-frictionless articulation and to distribute loads evenly to the underlying bone of the femur and tibia. In addition, the menisci provide stability to the injured knee when the cruciate ligaments or other primary stabilizers are deficient. The ability to perform these mechanical functions is based on the intrinsic material properties of the menisci as well as their gross anatomic structure and attachments. The material properties of the menisci are determined by their biochemical composition and, perhaps more important, by the organization and interactions of the major tissue constituents: water, proteoglycan, and collagen. Interactions among the important constituents of the fibrocartilage matrix cause meniscal tissue to behave as a fiber-reinforced, porous, permeable composite material similar to articular cartilage, in which frictional drag caused by fluid flow governs its response to dynamic loading. The menisci are one-half as stiff in compression and dissipate more energy under dynamic loading than articular cartilage. Energy dissipation, or shock absorption, by the menisci is the result of high frictional drag caused by low permeability of the matrix, which is about one-sixth as permeable as articular cartilage. The dynamic shear modulus of meniscal tissue is only one-fourth to one-sixth as great as that of articular cartilage. The coarse, circumferential Type I collagen fiber bundles of the meniscus give the tissue great tensile stiffness (range, 100-300 megapascals) and strength. The highly oriented collagen ultrastructure of the menisci makes the tissue anisotropic in tension, compression, and shear and appears to dominate its behavior under all loading conditions.

Collagen↗
PubMed1989

Material properties of the normal medial bovine meniscus.

The intrinsic compressive and tensile properties of normal bovine medial menisci were measured, and the variations in these properties with respect to the structural organization of the tissue and test specimen location were examined. Using a confined compression experiment, the compressive aggregate modulus and permeability of the meniscus were determined. The permeability of the tissue was also compared with the permeability as measured experimentally using a direct permeation experiment. Deep posterior specimens are significantly stiffer in compression than deep anterior and central-anterior specimens, while deep anterior specimens are significantly less stiff than deep posterior and central-posterior specimens. Posterior specimens have a significantly higher average water content. In addition, the permeability of the bovine meniscus was found to be about one-tenth that of bovine articular cartilage. The tensile stiffness of meniscal tissue was determined from constant strain rate uniaxial tension tests. To asses the directional variations in the tensile properties, specimens were obtained from the circumferential and radial orientations. The results indicate that the femoral surface of the meniscus is isotropic in tension, while specimens from within the meniscus are anisotropic--the circumferential specimens are much stiffer than the radial specimens. Furthermore, circumferential posterior specimens from the interior of the meniscus are significantly stiffer than similar anterior specimens. Layer inhomogeneities in the tensile properties with respect to distance from the femoral surface are also present.

Animals↗
PubMed1989

The total condylar prosthesis. 10- to 12-year results of a cemented knee replacement.

Over a two-year period 104 patients had 130 knee arthroplasties performed with the total condylar prosthesis at the Hospital for Special Surgery. At a 10- to 12-year review 58 patients (74 knees) had survived and were available for detailed clinical and radiographic evaluation. Of these, 38 knees (51.3%) were rated as excellent and 27 (36.5%) good. There were three (4.0%) fair and six (8.2%) poor results. Five of the six had had revision operations. The success of this early pattern of prosthesis supports the continued use of methacrylate cement for knee arthroplasties.

Adult↗
PubMed1987

Saturation analysis of cellular retinoid binding proteins: application to retinoic acid resistant human neuroblastoma cells and to human tumors.

A method for saturation analysis of cellular retinoic acid and retinol binding proteins, CRABP and CRBP, respectively, in cultured cells and human tumor samples, and its application to a retinoic acid resistant subline of the human neuroblastoma LA-N-5 cell line is described. Assessment of retinoid binding was accomplished by incubation of cytosols with increasing concentrations of [3H]retinoid (28-43 Ci/mmol; 1 Ci = 37 GBq) for 24 h. Bound retinoid was separated from free retinoid by adsorption with dextran-coated charcoal. Nonspecific binding was quantitated in parallel incubations which had been treated with p-chloromercuribenzene sulfonate (PCMBS), resulting in selective elimination of sulfhydryl-dependent ligand binding to both CRABP and CRBP. Quantitation was accomplished by Scatchard analysis of specific (PCMBS sensitive) binding. Employing this technique, specific retinoid binding was attributed to the presence of 2S macromolecules which displayed the known properties of CRABP and CRBP, namely ligand specificity, saturability, high ligand affinity, and PCMBS sensitivity. The apparent dissociation constants (Kd) for retinoic acid binding in cytosols prepared from murine 3T6 fibroblasts, rat testes, and a human ovarian tumor were 7, 11, and 35 nM, respectively. These preparations also bound retinol with high affinity, exhibiting Kds of 12, 26, and 48 nM, respectively. A retinoic acid resistant subline of LA-N-5 cells designated LA-N-5-R9 was established by long-term culture in the presence of 10(-6) M retinoic acid. This subline is resistant to the effects of retinoic acid in that it requires a 10-fold higher concentration of retinoic acid for 50% inhibition of growth than the parent line and displays no retinoic acid induced morphologic differentiation. Saturation analysis of CRABP in the parent and resistant subline reveal no significant alteration in either CRABP content or affinity. These results indicate that resistance to retinoic acid induced differentiation in LA-N-5-R9 occurs distal to CRABP binding or that CRABP does not mediate this response to retinoic acid.

4-Chloromercuribenzenesulfonate↗
PubMed1987

cis-Retinoic acid stimulates the clonal growth of some myeloid leukemia cells in vitro.

We studied the effects of cis-retinoic acid (cisRA) on the clonogenic growth of samples of leukemic cells from 35 patients with acute nonlymphocytic leukemia (ANLL). We observed significant inhibition of leukemic colony growth in 17 samples by 10(-7) to 10(-6)M cisRA. However, we found that retinoid exposure resulted in striking stimulation of clonal growth in ten samples at the same drug concentrations. With the exception of cases with promyelocytic features, there was no morphologic or functional evidence that cisRA induced the leukemic blasts to differentiate. Both inhibition and stimulation were dose-dependent and observable at pharmacologically achievable levels of cisRA. Leukemic cells with monocytic features more frequently demonstrated a stimulatory response than did those without monocytic features. Depletion of T lymphocytes and monocytes did not alter the type of growth response. Assays for cellular retinoic acid-binding protein (CRABP) were performed on five samples (two with inhibitory growth responses, two with stimulatory responses, and one with no growth) and failed to reveal detectable levels of CRABP in any case. The addition of cisRA to liquid suspensions of leukemic cells produced no significant change in the number of viable cells. We conclude that the effects of cisRA on leukemic colony growth are not cytotoxic and not mediated by T lymphocytes, monocytes, or CRABP. More importantly, cisRA appears to enhance the growth of certain human leukemia cells in vitro. Taking into account the increasing use of retinoids in clinical trials for patients with leukemia, the latter findings may represent a significant cautionary note.

Bone Marrow↗
PubMed1986

1,25-Dihydroxyvitamin D3 receptors: altered functional domains are associated with cellular resistance to vitamin D3.

1,25-Dihydroxyvitamin D3 receptors are cytosoluble proteins detectable in a variety of tissues responsive to 1,25(OH)2D3. They are DNA binding-proteins analogous to other steroid receptors and it is this functional property which is likely involved in the activation of hormone-sensitive genes. Utilizing 1,25(OH)2D3 and DNA binding assays, as well as anti-receptor monoclonal antibodies, we have probed the relationship between the 1,25(OH)2D3 receptor binding domains after selective cleavage with trypsin. These studies reveal that the hormone and DNA binding regions are separable, and are consistent with the finding that tissue resistance to 1,25(OH)2D3 is a result of structural defects in these domains. Recently, a primate model, the LLC-MK2 monkey kidney line, has been uncovered which may exemplify a hormone-binding defect. Here, 25-hydroxyvitamin D3-24-hydroxylase induction, a 1,25(OH)2D3 bioresponse, requires 100-fold higher concentrations of the hormone for maximal response. Concomitantly, this cell contains a variant receptor form which displays a correspondingly lowered apparent affinity for the hormone despite its seemingly normal DNA binding characteristics. Taken together, these studies suggest that the 1,25(OH)2D3 receptor is a macromolecule with multiple domains each of which may produce modified cellular resistance to 1,25(OH)2D3 if structurally altered.

Animals↗
PubMed1985

A variant form of the 1,25-dihydroxyvitamin D3 receptor with low apparent hormone affinity in cultured monkey kidney cells (LLC-MK2). A model for tissue resistance to vitamin D.

Chandler et al. (Chandler, J.S., Chandler, S.K., Pike, J.W., and Haussler, M.R. (1984) J. Biol. Chem. 259, 2214-2222) previously demonstrated that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) caused the induction of 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) in a rhesus monkey kidney cell line (LLC-MK2) apparently deficient in the high affinity 1,25-(OH)2D3 receptor. We have re-examined this phenomenon and report here that 24-hydroxylase induction is mediated by a receptor variant in LLC-MK2 cells with low hormone affinity. Dose response analysis showed that in contrast to LLC-PK1 (a typical receptor-positive cell line), the LLC-MK2 line was less sensitive to 1,25-(OH)2D3 by 2 orders of magnitude. Employing optimal concentrations of 1,25-(OH)2D3 for 24-hydroxylase induction in each cell type, the early time courses of this bioresponse were identical in LLC-MK2 and LLC-PK1 and were consistent with a nuclear action of hormone-receptor complexes. Moreover, the rank order of potency of vitamin D3 congeners as inducers of 24-hydroxylase activity in LLC-MK2 cells agreed well with their relative affinity for the 1,25-(OH)2D3 receptor. An examination of 1,25-(OH)2D3 receptor content via DNA-cellulose chromatography in LLC-MK2 cells incubated at ligand concentrations 10-25-fold higher than the normal 2 nM revealed a minimum of 1600 receptor-like molecules/LLC-MK2 cell. These results show that LLC-MK2 cells possess a variant receptor form with apparent low affinity for 1,25-(OH)2D3. This system should serve as a model for clinical syndromes characterized by the requirement for massive doses of vitamin D to prevent rickets.

24,25-Dihydroxyvitamin D 3↗
PubMed1979

Effects of high-LET neon (20Ne) particle radiation on the brain, eyes and other head structures of the pocket mouse: a histological study.

A study was made of tissues from 130 pocket mice after a single head-only exposure to high-LET 20Ne particle radiation at 1000, 100 or 10 rad (nominal surface dose) with the view of obtaining base"line data regarding the effectiveness of HZE (cosmic-ray) particles during spaceflight. First seen at 2-3 weeks after exposure, necrotic neurons in the cerebrum reached peak incidence (0 . 04 per cent at 1000 rad, 0 . 003 per cent at 100 rad and less than 0 . 0005 per cent at 10 rad) after 4-5 weeks and decreased to low levels thereafter. Incidence in the cerebellum was lower. Neuroglia, cells of the subependymal matrix and dentate gyrus precursor cells suffered acute damage at 1000 and at 100 rad. At 1000 rad, enlarged hyperchromatic neuroglia, first noted at 3 weeks, increased in number up to 7 months, then declined. Alterations in the retina and olfactory epithelium were seen at 1000 rad, and reaction in the scalp at 100 rad. Damage was incurred by dentinoblasts at 10 rad. Changes similar to those observed in pocket mice were found in the brains of gerbils and C57B1 mice.

Animals↗