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Biomedical subjects

M A Kelly

Publications and source records attributed to M A Kelly.

At least 55 records · Page 3Linked to original sources
PubMed1998

Idiopathic anaphylaxis in children.

BACKGROUND: Idiopathic anaphylaxis is a disease where no identifiable antigen or disease initiates an anaphylactoid reaction. Unlike classic IgE antibody-mediated anaphylaxis, severe idiopathic anaphylaxis is treatable with corticosteroids. To date, only 22 pediatric cases from one referral center have been reported. OBJECTIVE: To describe the characteristics of children with idiopathic anaphylaxis METHODS: A retrospective review of medical records for children presenting to the pediatric allergy clinic with the diagnosis of idiopathic anaphylaxis was performed. RESULTS: The review identified eight children with idiopathic anaphylaxis. All eight patients had a cutaneous finding of either urticaria, angioedema, or generalized flushing. Six of the eight patients were noted to have wheezing or angioedema of the airway causing respiratory difficulties. Diarrhea was noted among six patients. Many of the children clearly had life threatening events. Response to appropriate therapy was generally good. CONCLUSIONS: Pediatric idiopathic anaphylaxis can present at any age. It may be that many pediatric cases are assumed to be anaphylaxis due to some unknown antigen, and the correct diagnosis is never appreciated. It is important to recognize this disease in children so that it may be appropriately treated, because its specific therapeutic regimen has been shown to prevent the potentially fatal consequences of this disease.

Adolescent↗
PubMed1998

Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors.

Although dopaminergic transmission has been strongly implicated in alcohol self-administration, the involvement of specific dopamine receptor subtypes has not been well established. We studied the ethanol preference and sensitivity of D2-receptor-deficient mice to directly evaluate whether dopamine D2 receptors contribute to alcohol (ethanol) consumption. We report a marked aversion to ethanol in these mice, relative to the high preference and consumption exhibited by wild-type littermates. Sensitivity to ethanol-induced locomotor impairment was also reduced in these mutant mice, although they showed a normal locomotor depressant response to the dopamine D1 antagonist SCH-23390. These data demonstrate that dopamine signaling via D2 receptors is an essential component of the molecular pathway determining ethanol self-administration and sensitivity.

Alcohol Drinking↗
PubMed1998

Pharmacotherapy: strategies to control drug costs in managed care.

Pharmacotherapy remains one of the most cost-effective interventions physicians can provide to manage the medical conditions of older patients. Because many older Americans have multiple diseases, the practitioner's goal is to maximize appropriate drug use while avoiding duplicative or interacting medications. Medicare managed care plans seek to provide appropriate medication for the older patient at a reasonable cost through such strategies as formularies, prior authorization, generic and therapeutic substitution, and drug utilization review. Yet, like the medications themselves, these strategies require careful attention to their risks and benefits to the individual patient.

Drug Costs↗
PubMed1997

Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides.

The effects of pituitary-derived melanocortin peptides are primarily attributed to ACTH-mediated adrenocortical glucocorticoid production. Identification of a widely distributed receptor for ACTH/MSH peptides, the melanocortin-5 receptor (MC5-R), suggested non-steroidally mediated systemic effects of these peptides. Targeted disruption of the MC5-R produced mice with a severe defect in water repulsion and thermoregulation due to decreased production of sebaceous lipids. High levels of MC5-R was found in multiple exocrine tissues, including Harderian, preputial, lacrimal, and sebaceous glands, and was also shown to be required for production and stress-regulated synthesis of porphyrins by the Harderian gland and ACTH/MSH-regulated protein secretion by the lacrimal gland. These data show a requirement for the MC5-R in multiple exocrine glands for the production of numerous products, indicative of a coordinated system for regulation of exocrine gland function by melanocortin peptides.

Animals↗
PubMed1997

Arthroscopic treatment of the degenerative knee in older athletes.

The role of arthroscopy in the management of degenerative knee arthritis in the older athlete remains controversial. This patient population desires symptomatic improvement to maintain active lifestyles. For advanced tricompartmental osteoarthritis, total knee arthroplasty provides the most predictable results. For active patients with unicompartmental disease, osteotomy can provide symptomatic improvement and delay the time to total knee arthroplasty. Substantial morbidity is associated with both of these procedures. Arthroscopic management of degenerative arthritis is an attractive alternative to osteotomy or total knee arthroplasty if predictable improvement and durable results can be achieved. Arthroscopic lavage success rates are quite variable and decline rapidly over time. It is mainly a palliative procedure with limited long-term success. Success rates for arthroscopic partial meniscectomy and arthroscopic débridement vary between 50% and 75% depending on many factors, including the age of the patient, degree of arthritis, activity level of the patient, limb alignment, and extent of follow-up. Lavage is probably an important aspect of this procedure. Abrasion arthroplasty and the Pridie procedure do not appear to offer any additional benefit to arthroscopic débridement alone. In fact, studies comparing arthroscopic abrasion with arthroscopic débridement have shown that débridement alone gives better long-term results than débridement combined with abrasion. Several studies have shown that some patients become significantly worse following abrasion arthroplasty. Clearly, arthroscopic débridement is the preferred procedure to abrasion arthroplasty. The arthroscope is useful in the treatment of degenerative arthritis of the knee. It has low morbidity and does not preclude future reconstructive procedures. Although long-term success is difficult to predict, certain patient variables are associated with a better outcome: normal limb alignment, history of mechanical symptoms, minimal radiographic signs of degeneration, and short duration of symptoms. Long-term randomized prospective studies are needed to define the role of arthroscopy further in the older athlete with degenerative knee arthritis.

Adult↗
PubMed1997

The efficacy of arthroscopy following total knee replacement.

We evaluated the utility and safety of arthroscopy for diagnosing and treating symptoms in problematic total knee replacements. From 1988 to 1995, 40 arthroscopies were performed on 38 patients with an average age of 68.4 years. The average onset of symptoms post knee replacement was 33.7 months (range 1 month to 15 years), and the average duration of symptoms prior to arthroscopy was 15.6 months (range 1 month to 5 years). Presenting symptoms included pain in 73%, catching or soft tissue impingement in 35%, and stiffness in 20% of patients. Our protocol involves 24 hours of perioperative, intravenous antibiotics, and two or three routine arthroscopic portals. There were no arthroscopy-related complications or infections. Arthroscopy successfully diagnosed the etiology of the patient's symptoms in all but one case (97.5%). Operative diagnoses included impinging soft tissue under the patella consistent with the "clunk" syndrome (43%), impinging hypertrophic synovitis elsewhere in the knee (15%), impinging PCL stump (10%), prosthesis loosening or wear (10%), and arthrofibrosis (20%). Arthroscopic treatment consisted of removal of impinging tissue or loose body as indicated. Additionally, eight of the patients had a manipulation under anesthesia with an average improvement in flexion of 26.3 degrees postoperatively. At an average follow-up of 19.9 months, 27.5% of knees had developed recurrent symptoms. Two of these patients had repeat arthroscopy for recurrent impinging hypertrophic synovitis. The rates of successfully relieving symptoms without recurrence according to operative diagnosis were 82% for "clunks," 60% for other impinging synovium or soft tissue, and 63% for arthrofibrosis. Three patients underwent total knee revisions. Knees were rated at follow-up using the Knee Society rating system with patients divided according to functional category. The average Knee Society knee scores and function scores respectively were 93 and 92 for group A patients, 91 and 88 for group B patients, and 81 and 76 for group C patients. Arthroscopy successfully identified all cases of soft tissue impingement and prosthetic loosening or wear, and successfully treated 73% of patients without recurrence. There were no arthroscopy associated complications or infections. Thus, arthroscopy is a safe, effective tool for managing certain problematic knee replacements, especially "clunks," and may help to avoid revision or arthrotomy in some cases.

Aged↗
PubMed1997

Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice.

Dopamine secreted from hypophysial hypothalamic neurons is a principal inhibitory regulator of pituitary hormone secretion. Mice with a disrupted D2 dopamine receptor gene had chronic hyperprolactinemia and developed anterior lobe lactotroph hyperplasia without evidence of adenomatous transformation. Unexpectedly, the mutant mice had no hyperplasia of the intermediate lobe melanotrophs. Aged female D2 receptor -/- mice developed uterine adenomyosis in response to prolonged prolactin exposure. These data reveal a critical role of hypothalamic dopamine in controlling pituitary growth and support a multistep mechanism for the induction and perpetuation of lactotroph hyperplasia, involving the lack of dopamine signaling, a low androgen/estrogen ratio, and a final autocrine or paracrine "feed-forward" stimulation of mitogenesis, probably by prolactin itself.

Animals↗
PubMed1997

The Internet and randomised controlled trials.

Several factors constrain the implementation of Randomised Controlled Trials (RCTs). To obtain large sample sizes a multicentred multinational trial may be necessary or a long sampling period. The larger the trial the larger is the unit cost. To allow larger sample sizes, shorter sampling periods and lower unit costs, new methods are needed. The Internet and in particular the WWW provides such an opportunity. The WWW can provide global access, fast interaction and automation. A prototype Internet Trials Service (ITS) is currently being tested with a real international clinical trial (the Growth Restriction Intervention Trial--GRIT). The ITS is hosted on a Web server. It provides a series of HTML documents that describe the GRIT protocol. Registered centres may enter patients into the GRIT trial via ITS. Java applets are used to collect trial data before returning the study number and randomisation. ITS assumes all trial data will be intercepted by a sniffer. Therefore no information is sent that could specifically identify a patient, this must be sent later by more secure means. ITS assumes that trial centres can be spoofed. To authenticate the patients entered into the trial and the trial data sent, a regular audit report is sent to each centre by secure means for confirmation. By using Java, a full functional data entry system can be developed that runs locally within any Java enabled browser. It can perform data validation locally and also provide a sophisticated user interface.

Child Development↗
PubMed1996

Characterization of SH2-ligand interactions via library affinity selection with mass spectrometric detection.

Synthetic combinatorial libraries have proven to be a valuable source of diverse structures useful for large-scale biochemical screening. Their use has greatly facilitated the study of protein-protein interactions. We have developed a practical technique for screening such libraries by integrating affinity chromatography selection with electrospray ionization mass spectrometric detection, referred to as library affinity selection-mass spectrometry (LAS-MS). The process allows for rapid and efficient screening of solution phase libraries and provides detailed information such as the relative affinities of substrates. The method is generally applicable to include nonpeptide libraries; moreover, electrospray tandem mass spectrometry (ES-MS/MS) yields sequence-specific identification of individual components without the need for chemical tags. This technique is demonstrated using the Src homology 2 (SH2) domain of phosphatidylinositol 3-kinase (PI 3-kinase). The critical importance of methionine in the position +3 (relative to the phosphotyrosine position) is demonstrated in a library built with a phosphotyrosine mimic, (phosphonodifluoromethyl)phenylalanine. The described method has broad applicability to combinatorial library screening.

Amino Acid Sequence↗
PubMed1996

Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene.

Fanconi anemia (FA) is an autosomal recessive chromosome instability syndrome characterized by progressive bone marrow (BM) failure, skeletal defects, and increased susceptibility to malignancy. FA cells are hypersensitive to DNA cross-linking agents, oxygen and have cell cycle abnormalities. To develop an animal model of the disease we generated mice homozygous for a targeted deletion of exon 9 of the murine FA complementation group C gene (fac). Mutant mice had normal neonatal viability and gross morphology, but their cells had the expected chromosome breakage and DNA cross-linker sensitivity. Surprisingly, male and female mutant mice had reduced numbers of germ cells and females had markedly impaired fertility. No anemia was detectable in the peripheral blood during the first year of life, but the colony forming capacity of marrow progenitor cells was abnormal in vitro in mutant mice. Progenitor cells from fac knock-out mice were hypersensitive to interferon gamma. This previously unrecognized phenotype may form the basis for BM failure in human FA.

Animals↗
PubMed1996

Osteoblast adhesion to orthopaedic implant alloys: effects of cell adhesion molecules and diamond-like carbon coating.

In total joint arthroplasty, long-term outcomes depend in part on the biocompatibility of implant alloys. This study analyzed effects of surface finish and diamond-like carbon coating on osteoblast cell adhesion to polished titanium-aluminum-vanadium and polished or grit-blasted cobalt-chromium-molybdenum alloys. Osteoblast binding was tested in the presence and absence of the cell adhesion proteins fibronectin, laminin, fibrinogen, and vitronectin and was quantified by measurement of DNA content. Although adherence occurred in serum-free medium, maximal osteoblast binding required serum and was similar for titanium and cobalt alloys at 2 and 12 hours. With the grit-blasted cobalt alloy, cell binding was reduced 48% (p < 0.05) by 24 hours. Coating the alloys with diamond-like carbon did not alter osteoblast adhesion, whereas fibronectin pretreatment increased cell binding 2.6-fold (p < 0.05). In contrast, fibrinogen, vitronectin, and laminin did not enhance cell adhesion. These results support the hypothesis that cell adhesion proteins can modify cell binding to orthopaedic alloys. Although osteoblast binding was not affected by the presence of diamond-like carbon, this coating substance may influence other longer term processes, such as bone formation, and deserves further study.

Alloys↗
PubMed1996

Amniotic fluid meconium: a fetal environmental hazard.

OBJECTIVE: To investigate the hypothesis that meconium aspiration syndrome, the major hazard of meconium during labor, may be associated with superimposed fetal acute acidemia. METHODS: Umbilical artery blood gases were measured in 7816 term pregnancies with meconium in the amniotic fluid (AF) and the results were correlated with intrapartum and neonatal outcomes. RESULTS: Sixty-nine (1%) infants developed meconium aspiration syndrome and 31 (45%) of these were in association with fetal acidemia at birth. Moreover, umbilical blood gas analysis and intrapartum events suggested that the fetal acidemia linked to meconium aspiration was an acute event rather than a long-duration process, which might be expected if meconium was itself a marker of an antecedent fetal asphyxial event. CONCLUSION: Meconium in the AF may be a fetal environmental hazard when acidemia supervenes rather than solely a marker of preexisting fetal compromise leading to the release of meconium.

Acid-Base Imbalance↗
PubMed1996

Primary structure of bovine adenosine deaminase.

Derivatized bovine adenosine deaminase is used in enzyme replacement therapy and as an adjunct to gene therapy against severe combined immunodeficiency syndrome. Although a gene sequence is known for human adenosine deaminase, the structure of the bovine enzyme has not been characterized. Structure studies using mass spectrometry are reported here that evaluate sequence, processing, post-translational modifications and the extent of homology between the human protein and its therapeutic surrogate.

Adenosine Deaminase↗
PubMed1996

A study of oligoclonal band negative multiple sclerosis.

OBJECTIVES: To determine whether oligoclonal band (OCB) negative multiple sclerosis is a reliable diagnosis and, if so, whether it has a distinctive prognosis. METHODS: Retrospective and matched prospective comparison of the clinical and laboratory features of patients with clinical definite multiple sclerosis with and without intrathecal synthesis of oligoclonal IgG. RESULTS: Thirty four patients were identified with apparent OCB negative clinically definite multiple sclerosis. The results of oligoclonal banding proved to have been equivocal in 14 of 34; the clinical diagnosis of multiple sclerosis was questionable in 8 of 34. The remaining 12 patients with "true" OCB negative multiple sclerosis were significantly less disabled than matched OCB positive controls. Re-examination of CSF-serum pairs from six OCB negative patients showed that three remained OCB negative while three showed evidence of intrathecal synthesis of OCBs. CONCLUSIONS: OCB negative clinically definite multiple sclerosis is rare and should be diagnosed with caution; in unequivocal cases it seems to have a relatively benign prognosis.

Adult↗