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Biomedical subjects

K M Kelly

Publications and source records attributed to K M Kelly.

At least 55 records · Page 3Linked to original sources
PubMed1995

Cranioplasty in the growing canine skull using demineralized perforated bone.

This study was designed to test the hypothesis that demineralized perforated bone matrix implant from canine skull and tibia induces new bone formation within the calvarial defect comparable with the bone induced by autogenous graft. We also were interested in determining whether demineralized perforated bone matrix implants from membranous bone have greater osseoinductive capacity in the calvarial area than demineralized perforated bone matrix implants from endochondral bone. Forty 12-week-old purebred beagles were used. Group I consisted of animals with unrepaired surgically created calvarial defects healed by secondary intention (n = 10). Group II consisted of animals with surgically created calvarial defects in which the bone was removed and replaced with an autograft (n = 10). Group III consisted of animals with surgically created calvarial defects in which the bony defect was closed with a demineralized perforated bone matrix implant obtained from beagle calvaria (n = 10). Group IV consisted of animals with surgically created calvarial defects in which the bony defect was closed with a demineralized perforated bone matrix implant obtained from beagle tibia (n = 10). The two control groups (I and II) allowed us to isolate the inductive capacity of demineralized perforated bone matrix implants and compare it with the healing of the bone defects left unrepaired or repaired with calvarial autografts. Animals were sacrificed after 8 and 12 weeks. In the present study we were able to verify that demineralized perforated bone matrix implants are well accepted in the calvarial defects with little tissue reaction and remarkably little osteoclastic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Antiepileptic drug mechanisms of action.

Established antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed before 1980 appear to act on sodium channels, gamma-aminobutyric acid type A (GABAA) receptors, or calcium channels. Benzodiazepines and barbiturates enhance GABAA receptor-mediated inhibition. Phenytoin (PHT), carbamazepine (CBZ), and possibly valproate (VPA) decrease high-frequency repetitive firing of action potentials by enhancing sodium-channel inactivation. Ethosuximide (ESM) and VPA reduce a low threshold (T-type) calcium-channel current. The mechanisms of action of the new AEDs are not fully established. Gabapentin (GBP) binds to a high-affinity site on neuronal membranes in a restricted regional distribution of the central nervous system. This binding site may be related to a possible active transport process of GBP into neurons; however, this has not been proven, and the mechanism of action of GBP remains uncertain. Lamotrigine (LTG) decreases sustained high-frequency repetitive firing of voltage-dependent sodium action potentials that may result in a preferential decreased release of presynaptic glutamate. The mechanism of action of oxcarbazepine (OCBZ) is not known; however, its similarity in structure and clinical efficacy to CBZ suggests that its mechanism of action may involve inhibition of sustained high-frequency repetitive firing of voltage-dependent sodium action potentials. Vigabatrin (VGB) irreversibly inhibits GABA transaminase, the enzyme that degrades GABA, thereby producing greater available pools of presynaptic GABA for release in central synapses. Increased activity of GABA at postsynaptic receptors may underline the clinical efficacy of VGB.

Acetates↗
PubMed1995

Cardiac arrest following use of sumatriptan.

I report a 35-year-old woman with occult coronary artery disease who experienced cardiac arrest within minutes after receiving a first-time dose of subcutaneous sumatriptan for migraine. The patient was resuscitated, and subsequent serial cardiac enzymes indicated myocardial infarction. Because sumatriptan can cause coronary artery vasospasm, patients with significant risk factors for coronary artery disease should be carefully evaluated for cardiovascular disease prior to the use of sumatriptan.

Adult↗
PubMed1995

Periosteum in regeneration of palatal defects.

The influence of the periosteum on the regeneration of palatal bone was investigated in this study. Eighty, 8-week-old, purebred beagle dogs were assigned randomly to four groups: (1) unoperated dogs as a group control; dogs in which the mid-third of the palate was surgically removed and (2) left unrepaired (unrepaired controls); (3) repaired with mucosal flaps; (4) repaired with mucoperiosteal flaps. Five animals from each group were killed at 4, 6, 8, and 12 weeks after surgery and coronal sections examined under light microscopy. Among the animals with complete soft tissue healing, 8 of 12 dogs from Group 2, 11 of 20 from Group 3, and 10 of 19 from Group 4 showed complete bone regeneration. No significant differences were found overall in bone thickness and bone density measurements between Group 3 and Group 4. Histologically, a well-differentiated periosteum was present on the maxilla at 4 weeks, even in animals in which the periosteum had not been preserved in the original flap. These results suggest that maintaining the periosteum at surgical closure does not influence bone regeneration in beagles up to 12 weeks of age. We suggest that osteoprogenitor cells, migrating from the undisturbed local periosteum adjacent to the defect, were responsible for the new bone growth in our study.

Analysis of Variance↗
PubMed1995

Comparison of fura-2 imaging and electrophysiological analysis of murine calcium channel alpha 1 subunits coexpressed with novel beta 2 subunit isoforms.

A polymerase chain reaction product was used to isolate mouse brain cDNA clones coding for isoforms of the beta subunit of voltage-dependent Ca2+ channels. The two mouse brain beta 2 subunit cDNA clones described, beta 2a and beta 2b, differed by alternative splicing within the coding region but possessed a unique amino terminus not yet reported in other beta 2 subunit cDNAs. Northern blot and RNase protection analyses demonstrated that both mRNA isoforms could be detected in highest abundance in heart and brain and at lower levels in lung, kidney, and testis. In a novel assay for beta 2 subunit function, COS-1 cells were transfected with alpha 1 and beta 2 subunit expression vectors and assayed for increases in intracellular Ca2+ concentration by using fura-2 imaging. Co-transfection of COS-1 cells with the mouse brain class C-1 alpha 1 subunit expression vector and either of the beta 2 subunit expression vectors resulted in increases in intracellular Ca2+ concentration after stimulation with elevated K+ and the dihydropyridine agonist Bay K 8644. Transfection of either alpha 1 or beta 2 subunit expression vectors alone did not result in an elevation of intracellular Ca2+ concentration. Electrophysiological recording of human embryonic kidney 293 cells transfected with the expression vector for the alpha 1 subunit alone or with either beta 2 subunit demonstrated expression of voltage-dependent Ca2+ channels that were dihydropyridine sensitive. Currents formed by expression of only the alpha 1 subunit were small and slowly inactivated. In contrast, the currents formed by coexpression of alpha 1 subunits with either beta 2 subunit were larger and inactivated more rapidly. Dihydropyridine binding studies demonstrated that coexpression of alpha 1 subunits with beta 2 subunits increased the density of functional receptors, compared with expression of alpha 1 subunits alone. These experiments suggested that coexpression of the alpha 1 and beta 2 subunits produced functional dihydropyridine-sensitive Ca2+ channels and that both beta subunit isoforms had modulatory effects on these channels.

Amino Acid Sequence↗
PubMed1994

Successful in vivo immunolocalization of Langerhans cell histiocytosis with use of a monoclonal antibody, NA1/34.

The antibody NA1/34 is a murine monoclonal antibody directed against the CD1a surface antigen expressed on normal Langerhans cells, cortical thymocytes, and on lesional cells in Langerhans cell histiocytosis (LCH). Our hypothesis was that NA1/34 would localize sites of disease activity in patients with multisystem LCH. To test this hypothesis, indium 111-labeled NA1/34 was administered to five patients with multisystem LCH and serial gamma scans were obtained for up to 120 hours. Serial serum samples were obtained from one patient for analysis of anti-mouse Ig antibody and NA1/34 levels. Direct and indirect immunofluorescence staining for CD1a and NA1/34 were performed on a tissue biopsy specimen from one patient after administration of the antibody. The 1- and 4-hour scans showed distribution of antibody in the blood pool, but in later scans localization of the antibody was noted in areas of known disease activity in all five patients. Bony lesions, previously seen on skeletal radiographs, were especially well identified. Serum kinetics studies showed clearance of the antibody from the blood pool within 12 hours of administration. Direct binding of NA1/34 to lesional cells was demonstrated by direct immunofluorescence. The only adverse effect was urticaria in one patient. We conclude that NA1/34 localizes disease activity in vivo in bones of patients with LCH with minimal toxic effects. An evaluation of its role in determining disease extent ("staging") and in treatment is now needed.

Adult↗
PubMed1994

Relationship between the sequence of lip and palate repair and maxillary growth: an experimental study in beagles.

The present study was designed to evaluate the relationship between varying sequences of lip and palate repair and maxillary growth. To investigate this problem, an experimental study using beagles was conducted to assess the influence of three different sequences of lip and palate repair. The first sequence constitutes the commonly accepted approach of lip repair first, palate repair second. The second sequence was reversed: palate repair first, lip repair second. The third sequence consisted of simultaneous lip and palate repair. Using 70 eight-week-old beagles, we tested the following hypothesis: The sequence of lip repair first and palate repair second is less detrimental to maxillary growth than the other two sequences. The animals were assigned to two control groups (unoperated and unrepaired animals) and three experimental groups, in which three different sequences of repair were executed. Upon sacrifice, 11 maxillary variables were measured directly from cleaned skulls and analyzed by univariate and multivariate techniques. The most important finding from this analysis is that the commonly accepted sequence of cleft lip and palate repair (lip first, palate second) is less detrimental to maxillary growth than repairing the palate first and the lip second or simultaneous closure of both defects.

Analysis of Variance↗
PubMed1994

A comparative study of the effects of biodegradable and titanium plating systems on cranial growth and structure: experimental study in beagles.

An experimental study was conducted in beagles to assess the effects of biodegradable and titanium plating systems on cranial growth and structure. Forty-eight 9-week-old purebred beagles were used in this study. To avoid any effects of sexual dimorphism, we used only female beagles. The animals were divided in three groups: sham-operated controls, n = 16; beagles implanted with commercially available titanium plates and screws, n = 16; and beagles implanted with biodegradable plates and screws, n = 16. The biodegradable plating system developed by Storz Instrument Company (St. Louis, Mo.) for use in the craniofacial skeleton does not require another procedure to remove plates and screws once the healing process is completed. To assess the dynamics of changes in cranial growth under the influence of two different plating systems, we conducted two identical studies during two different time periods: 6 weeks and 12 weeks. Using two different time frames allowed us to assess changes in the biodegradable material and in the bone and soft tissue surrounding this material. Statistical analysis revealed no significant differences in the gross cranial structure among the three groups. This finding suggests that the biodegradable plating system has no adverse effect on cranial growth. The material does resorb and/or disintegrate between 6 and 12 weeks after insertion. The rate of resorption is approximately 5.3 microns per day. The bone and soft tissue surrounding the biodegradable implant exhibited very limited inflammation and foreign body reaction. Bony overgrowth was frequently found over the plating system.

Animals↗
PubMed1994

The effects of lip repair with and without soft-tissue undermining and delayed palate repair on maxillary growth: an experimental study in beagles.

Undermining of the soft tissue on the surface of the maxilla at the time of cleft lip repair remains a controversial issue in cleft management. Using 64 eight-week-old beagles, we tested the hypothesis that lip repair with soft-tissue undermining contributes more to maxillofacial growth aberrations than lip repair without these additional procedures. Animals were assigned to four groups: unoperated controls, unrepaired controls, and two experimental groups (with and without undermining). Defects simulating cleft of the lip, alveolus, and palate were surgically created in the unrepaired and experimental animals. At 36 weeks of age, 11 measurements were made directly on the cleaned maxillae. Analysis revealed that all groups with surgically created defects were significantly different from normal; however, animals with undermining exhibited the greatest group deviation from normal. These findings reaffirm our earlier conclusions that undermining of the soft tissue on the surface of the maxilla is detrimental to maxillofacial growth.

Analysis of Variance↗
PubMed1994

Mechanisms of action of currently prescribed and newly developed antiepileptic drugs.

Clinically available antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed before 1980 appear to act on sodium (Na) channels, gamma-aminobutyric acid A (GABAA) receptors, or calcium (Ca) channels. Benzodiazepines and barbiturates enhance GABAA-receptor-mediated inhibition. Phenytoin, carbamazepine and, possibly, valproate (VPA) decrease high-frequency repetitive firing of action potentials by enhancing Na channel inactivation. Ethosuximide and VPA reduce a low threshold (T-type) Ca-channel current. The mechanisms of action of recently developed AEDs are less clear. Lamotrigine may decrease sustained high-frequency repetitive firing of voltage-dependent Na action potentials, and gabapentin (GBP) appears to bind to a specific binding site in the CNS with a restricted regional distribution. However, the identity of the binding site and the mechanism of action of GBP remain uncertain. The antiepileptic effect of felbamate may involve interaction at the strychnine-insensitive glycine site of the N-methyl-D-aspartate receptor, but the mechanism of action is not yet proven.

Acetates↗
PubMed1994

Monoclonal antibody therapy in Langerhans cell histiocytosis--feasible and reasonable?

Many recent studies have demonstrated the range of disorders in which monoclonal antibodies have a clinical role. The monoclonal antibody NA1/34, directed against a surface antigen present on lesional cells ('LCH cells'), has been found to localise in vivo to sites of disease. This review explores the possible applications and limitations of monoclonal antibody based-therapy in Langerhans cell histiocytosis.

Antibodies, Monoclonal↗
PubMed1993

Biological response modifier-mediated resistance to herpesvirus infections requires induction of alpha/beta interferon.

The role of interferon alpha/beta (IFN) induction by the immunomodulators pICLC and CL246,738 was investigated in CD-1 mice infected with murine cytomegalovirus (MCMV) or herpes simplex virus type 2 (HSV-2). Mice were treated with either normal sheep serum or anti-alpha/beta IFN antiserum, inoculated with the immunomodulators, and infected with virus. Because anti-IFN treatment also decreased natural resistance to HSV-2 and MCMV, two viral challenge doses were used to ensure that the mice with control serum or anti-IFN antiserum received biologically equivalent infections. Antiviral protection of pICLC and CL246,738 against HSV-2 infection was completely abrogated by treatment with anti-alpha/beta interferon antiserum. Mice treated with pICLC also lost antiviral protection against MCMV when interferon alpha/beta was depleted. These results indicate that induction of interferon alpha/beta appears to be a major mechanism for both natural resistance and pICLC-induced antiviral protection against MCMV and HSV-2 herpesvirus infections.

Acridines↗
PubMed1993

Gabapentin actions on ligand- and voltage-gated responses in cultured rodent neurons.

Gabapentin (GBP) is a cyclic gamma-aminobutyric acid (GABA) analog and investigational antiepileptic drug which is effective in the treatment of a variety of human and experimental seizures. GBP's antiepileptic mechanism of action is not known. The present studies tested for effects of GBP on inhibitory (GABA and glycine) and excitatory (N-methyl-D-aspartate (NMDA) and non-NMDA) amino acid neurotransmitter receptors, on repetitive firing of sodium (Na+) action potentials, and on voltage-dependent calcium (Ca2+) channel currents in cultured rodent neurons using intracellular, whole cell, or single channel recording techniques. GBP did not have a significant effect in any experiment when tested at or above concentrations that are therapeutic in humans except for a variable enhancement of NMDA-evoked depolarizations. These results suggest that the antiepileptic activity of GBP is not due to direct effects at receptors for inhibitory or excitatory amino acids or on voltage-dependent Na+ or Ca2+ channels.

Acetates↗
PubMed1993

The utility of routine daily chest radiography in the surgical intensive care unit.

Routine morning chest x-ray films (CXRs) are widely obtained in surgical intensive care unit (SICU) patients. During a 1-month time period we prospectively evaluated 525 routine morning CXRs in patients admitted to the SICU of a university trauma center (n = 256) or a suburban affiliate hospital (n = 269) to assess the impact of these CXRs on patient care. All CXRs were read by radiologists. Data on position of medical devices (CVP lines, endotracheal tubes, etc.) and cardiopulmonary (CP) findings were collected. A total of 1028 medical devices were evaluated. Fifty-five (5.4%) were considered to be in a minor incorrect position that did not adversely affect patient care and only 13 (1.3%) devices required repositioning for patient care or safety. Seventy-eight CXRs were read as normal. There were 775 CP findings on the remaining 477 CXRs. When compared with previous CXRs, only 12% (89 of 775) of the findings were considered new, 65% were unchanged, 14% were improved, and 15% demonstrated worsening of a known finding. Of the 89 new CP findings, only three had any potential clinical impact (pneumothorax in two, effusion in one). These data demonstrate an extremely low yield of clinically significant and unsuspected new CP findings or device malposition on the routine morning CXR. We conclude that routine daily chest radiography should be abandoned and that the need for a morning CXR should be based on clinical necessity.

Adult↗
PubMed1993

A comparative study of facial growth following lip and palate repair performed in sequence and simultaneously: an experimental study in beagles.

This study was designed to assess the effects of the commonly accepted sequence of cleft lip and palate repair on subsequent maxillofacial growth and to compare these effects with those resulting from simultaneous lip and palate repair. Using 62 eight-week-old normal beagles, we tested the hypothesis that sequential repair (lip first, palate second) of surgically induced lip and palate defects is less detrimental to maxillofacial growth than simultaneous repair of both surgically created defects. Animals were assigned to one of four groups: two control groups (unoperated and unrepaired) and two experimental groups. Defects simulating cleft of the lip, alveolus, and palate were surgically created in the unrepaired controls and in the experimental animals. In one experimental group, the lip and palate defects were repaired immediately and simultaneously. In the other experimental group--simulating current clinical practice--the lip defect was repaired first at the time that it was created, while closure of the palatal defect was delayed 4 weeks. After the animals were killed at 36 weeks of age, 11 maxillary variables were measured directly from cleaned skulls and analyzed by using univariate and multivariate techniques. Animals that had lip and palate defects closed in sequence had less severe maxillofacial aberrations than animals with simultaneously closed defects. Sequential closure of the defects also had identifiable effects on maxillofacial form. The growth aberrations observed among animals with sequential closure, however, are primarily attributable to surgical creation of the defects and not to the surgical repair. Delaying palate repair is less traumatic to the subsequent growth of the maxillary complex than simultaneous repair of lip and palate defects.

Animals↗
PubMed1993

Antiepileptic drug mechanisms of action.

Clinically used antiepileptic drugs (AEDs) decrease membrane excitability by interacting with ion channels or neurotransmitter receptors. Currently available AEDs appear to act on sodium channels, GABAA receptors, or calcium channels. Phenytoin, carbamazepine, and possibly valproate (VPA) decrease high-frequency repetitive firing of action potentials by enhancing sodium channel inactivation. Benzodiazepines and barbiturates enhance GABAA receptor-mediated inhibition. Ethosuximide and possibly VPA reduce a low-threshold calcium current. The mechanisms of action of AEDs currently under development are less clear. Lamotrigine may decrease sustained high-frequency repetitive firing. The mechanisms of action of felbamate are unknown. Gabapentin (GBP) appears to bind to a specific binding site in the central nervous system with a restricted regional distribution, but the identity of the binding site and the mechanism of action of GBP remain uncertain.

Acetates↗
PubMed1993

Multidisciplinary treatment results for patients with isolated cleft palate.

Fifty-eight patients with cleft palate only who had received treatment in the Department of Otolaryngology-Head and Neck Surgery at the University of Iowa were examined for treatment results. Forty-one (70.7 percent) of the 58 patients showed a syndrome or suggestive factors. An unusually high percentage (36 percent) of the 58 patients required secondary surgery for velopharyngeal dysfunction or showed indications for surgery at examination. Some but not all of the relatively low success rate appears related to surgical experience. Speech proficiency, hearing acuity, and dental status were within normal limits or nearly so. The 20 patients with pharyngeal flap surgery were doing well, with minimal indications of functional obstruction.

Adolescent↗