Biomedical subjects

L McKinley

Publications and source records attributed to L McKinley.

5 recordsLinked to original sources

PubMed2006

Anti-tumor necrosis factor-alpha antibody treatment reduces pulmonary inflammation and methacholine hyper-responsiveness in a murine asthma model induced by house dust.

BACKGROUND/AIMS: Recent studies documented that sensitization and exposure to cockroach allergens significantly increase children's asthma morbidity as well as severity, especially among inner city children. TNF-alpha has been postulated to be a critical mediator directly contributing to the bronchopulmonary inflammation and airway hyper-responsiveness in asthma. This study investigated whether an anti-TNF-alpha antibody would inhibit pulmonary inflammation and methacholine (Mch) hyper-responsiveness in a mouse model of asthma induced by a house dust extract containing both endotoxin and cockroach allergens. METHODS: A house dust sample was extracted with phosphate-buffered saline and then used for immunization and two additional pulmonary challenges of BALB/c mice. Mice were treated with an intravenous injection of anti-TNF-alpha antibody or control antibody 1 h before each pulmonary challenge. RESULTS: In a kinetic study, TNF-alpha levels within the bronchoalveolar lavage (BAL) fluid increased quickly peaking at 2 h while BAL levels of IL-4, IL-5, and IL-13 peaked at later time-points. Mch hyper-responsiveness was measured 24 h after the last challenge, and mice were killed 24 h later. TNF inhibition resulted in an augmentation of these Th2 cytokines. However, the allergic pulmonary inflammation was significantly reduced by anti-TNF-alpha antibody treatment as demonstrated by a substantial reduction in the number of BAL eosinophils, lymphocytes, macrophages, and neutrophils compared with rat IgG-treated mice. Mch hyper-responsiveness was also significantly reduced in anti-TNF-alpha antibody-treated mice and the pulmonary histology was also significantly improved. Inhibition of TNF significantly reduced eotaxin levels within the lung, suggesting a potential mechanism for the beneficial effects. These data indicate that anti-TNF-alpha antibody can reduce the inflammation and pathophysiology of asthma in a murine model of asthma induced by a house dust extract.

Allergens↗

PubMed2004

Reproducibility of a novel model of murine asthma-like pulmonary inflammation.

Sensitization to cockroach allergens (CRA) has been implicated as a major cause of asthma, especially among inner-city populations. Endotoxin from Gram-negative bacteria has also been investigated for its role in attenuating or exacerbating the asthmatic response. We have created a novel model utilizing house dust extract (HDE) containing high levels of both CRA and endotoxin to induce pulmonary inflammation (PI) and airway hyperresponsiveness (AHR). A potential drawback of this model is that the HDE is in limited supply and preparation of new HDE will not contain the exact components of the HDE used to define our model system. The present study involved testing HDEs collected from various homes for their ability to cause PI and AHR. Dust collected from five homes was extracted in phosphate buffered saline overnight. The levels of CRA and endotoxin in the supernatants varied from 7.1 to 49.5 mg/ml of CRA and 1.7-6 micro g/ml of endotoxin in the HDEs. Following immunization and two pulmonary exposures to HDE all five HDEs induced AHR, PI and plasma IgE levels substantially higher than normal mice. This study shows that HDE containing high levels of cockroach allergens and endotoxin collected from different sources can induce an asthma-like response in our murine model.

Allergens↗

PubMed1998

Phase I study of the mitomycin C analogue BMS-181174.

BMS-181174 is an aminodisulphide derivative of Mitomycin C (MMC) with activity against a range of tumour cell lines and xenografts, including MMC-resistant tumours. In a phase I study of 82 patients with confirmed malignancy, we administered BMS-181174 at doses of 0.8-75 mg m(-2) by intravenous injection every 28 days. At least three patients were evaluated at each dose level, and 174 courses were administered. The pharmacokinetics were dose linear at BMS-181174 doses of 11.5-75 mg m(-2) and the drug appeared to undergo wide distribution. The maximum-tolerated dose was 65 mg m(-2) in previously treated patients and 75 mg m(-2) in chemotherapy-naive cases. The dose-limiting toxicity was myelosuppression, particularly thrombocytopenia, which was prolonged and cumulative. Three patients treated at 65-75 mg m(-2) died suddenly with evidence of pneumonia/pneumonitis, thought to be drug-related. Other toxicities included thrombophlebitis, possible cardiotoxicity (asymptomatic, reversible decline in left ventricular function) and renal impairment. The partial response rate was 5% (4 out of 82) overall, and 9% (3 out of 32) in patients treated at 65-75 mg m(-2). Responses occurred in treated and previously-untreated patients, including cases of colorectal cancer, non-small-cell lung cancer, ovarian cancer and adenocarcinoma of unknown primary site. BMS-181174 has anti-cancer activity but, because of its toxicity, particularly pneumonitis and thrombophlebitis, no phase II studies are planned.

Adult↗

PubMed1993

Are baseline prothrombin time/partial thromboplastin time values necessary before instituting anticoagulation?

STUDY OBJECTIVES: To determine whether baseline prothrombin time (PT) or partial thromboplastin time (PTT) values provide information that is useful to the clinician before initiating anticoagulation and whether emergency physicians elicit historical information about bleeding disorders before beginning anticoagulant therapy. DESIGN: A three-year retrospective review of the records of 199 patients admitted through the ED with an ICD-9-CM diagnosis of deep-vein thrombosis or pulmonary embolus using a predesigned study sheet that included historical questions, baseline PT and PTT values, treatment given, timing of treatment, and underlying medical problems. SETTING: University-affiliated tertiary-care hospital. MEASUREMENTS AND MAIN RESULTS: Deep-vein thrombosis was the primary diagnosis in 75% of patients. Pertinent historical items were not documented in 92% to 100% of patients. Baseline PT and PTT values were obtained in 94% of patients. An elevated baseline PT was found in 26 patients, all of whom were taking warfarin. An elevated baseline PTT was found in 21 patients. These results were attributed to laboratory error (one), warfarin use (nine), heparin therapy before baseline tests (five), anticardiolipin antibodies (five, one of whom was on warfarin therapy), and unknown causes (three). Heparin therapy was not altered for any patient. CONCLUSION: Emergency physicians rarely document pertinent questions about bleeding disorders before initiating anticoagulation therapy. Baseline PT and PTT values are almost routinely obtained despite the fact that they do not alter therapy or serve as sensitive or specific screening tests. Routine baseline PT and PTT values are rarely needed before initiating anticoagulation. Eliminating such routine testing would result in significant cost savings.

Adolescent↗

PubMed1977

Myocardial creatine kinase isoenzyme in serum after subarachnoid haemorrhage.

The myocardial isoenzyme of creatine kinase (MB CK) has been demonstrated in the serum of seven of 16 patients presenting with acute subarachnoid haemorrhage. All patients with elevated MB CK levels exhibited at some stage either intracranial arterial spasm as demonstrated by cerebral angiography, or a focal reversible neurological deficit not due to direct pressure by either intracranial haematoma or aneurysm. The presence of MB CK isoenzymes in sera of patients with subarachnoid haemorrhage may be an index of cerebral ischaemia, and may thus be of value in determining optimal timing of surgery or, ultimately, the long-term prognosis. Changes in the sympathetic nervous system may be a common factor producing both MB isoenzyme release from the myocardium and intracranial arterial spasm.

Brain↗