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Biomedical subjects

L Knox

Publications and source records attributed to L Knox.

15 recordsLinked to original sources
PubMed2000

Annihilating cold dark matter

Structure formation with cold dark matter (CDM) predicts halos with a central density cusp, which are observationally disfavored. If CDM particles have an annihilation cross section sigmav approximately 10(-29)(m/GeV) cm(2), then annihilations will soften the cusps. We discuss plausible scenarios for avoiding the early Universe annihilation catastrophe that could result from such a large cross section. The predicted scaling of core density with halo mass depends upon the velocity dependence of sigmav, and s-wave annihilation leads to a core density nearly independent of halo mass, which seems consistent with observations.

Journal Article↗
PubMed2000

Characterizing the peak in the cosmic microwave background angular power spectrum

A peak has been unambiguously detected in the cosmic microwave background angular spectrum. Here we characterize its properties with fits to phenomenological models. We find that the TOCO and BOOM/NA data determine the peak location to be in the range 175-243 and 151-259, respectively (at 95% confidence) and determine the peak amplitude to be between approximately 70 and 90 &mgr;K. The peak shape is consistent with inflation-inspired flat, cold dark matter plus cosmological constant models of structure formation with adiabatic, nearly scale invariant initial conditions. It is inconsistent with open models and presents a great challenge to defect models.

Journal Article↗
PubMed2000

Dark energy and the cosmic microwave background radiation.

We find that current cosmic microwave background anisotropy data strongly constrain the mean spatial curvature of the Universe to be near zero, or, equivalently, the total energy density to be near critical-as predicted by inflation. This result is robust to editing of data sets, and variation of other cosmological parameters (totaling seven, including a cosmological constant). Other lines of argument indicate that the energy density of nonrelativistic matter is much less than critical. Together, these results are evidence, independent of supernovae data, for dark energy in the Universe.

Astronomy↗
PubMed1998

Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma.

Malignant pleural mesothelioma is a fatal neoplasm that is unresponsive to standard modalities of cancer therapy. We conducted a phase I dose-escalation clinical trial of adenoviral (Ad)-mediated intrapleural herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy in patients with mesothelioma as a model for treatment of a localized malignancy. The goals of this phase I trial were to assess the safety, toxicity, and maximally tolerated dose of intrapleural Ad.HSVtk, to examine patient inflammatory response to the viral vector, and to evaluate the efficiency of intratumoral gene transfer. Twenty-one previously untreated patients were enrolled in this single-arm, dose-escalation study with viral doses ranging from 1 x 10(9) plaque-forming units (pfu) to 1 x 10(12) pfu. A replication-incompetent recombinant adenoviral vector containing the HSVtk gene under control of the Rous sarcoma virus (RSV) promoter-enhancer was introduced into the pleural cavity of patients with malignant mesothelioma followed by 2 weeks of systemic therapy with GCV at a dose of 5 mg/kg twice a day. The initial 15 patients underwent thoracoscopic pleural biopsy prior to, and 3 days after, vector delivery. The last six patients underwent only the post-vector instillation biopsy. Dose-limiting toxicity was not reached. Side effects were minimal and included fever, anemia, transient liver enzyme elevations, and bullous skin eruptions, as well as a temporary systemic inflammatory response in those receiving the highest dose. Strong intrapleural and intratumoral immune responses were generated. Using RNA PCR, in situ hybridization, immunohistochemistry, and immunoblotting, HSVtk gene transfer was documented in 11 of 20 evaluable patients in a dose-related fashion. This study demonstrates that intrapleural administration of an adenoviral vector containing the HSVtk gene is well tolerated and results in detectable gene transfer when delivered at high doses. Further development of therapeutic trials for treatment of localized malignancy using this vector is thus warranted.

Adenoviruses, Human↗
PubMed1998

Treatment of adolescent gynecomastia using a bipedicle technique.

Many methods have been described for the treatment of gynecomastia. Eleven adolescent boys have been managed with a bipedicle technique. These patients were evaluated for nipple-areolar viability, scarring, patient satisfaction, and hematoma or seroma formation. The pedicles providing blood supply to the nipple-areolar complex are reliable and are derived from the dermis and glandular breast tissue, thus minimizing nipple-areolar necrosis and hypopigmentation as a complication of the procedure. A periareolar incision provides adequate exposure for safe dissection and excision of the breast tissue, and facilitates reduction in the complex if needed. Good to excellent results were reported in all 11 patients at 2 weeks to 13 months of follow-up. There was no evidence of nipple-areolar necrosis and only one case of postoperative seroma formation. This approach utilizes a safe and reliable method of breast reduction that is particularly effective in the male adolescent group.

Adolescent↗
PubMed1995

Morphologic change in rabbit femoral arteries induced by storage at four degrees Celsius and by subsequent reperfusion.

PURPOSE: Cold-stored arteries function well as microvascular autografts, but little is known of the morphologic changes that occur in them during cold storage or of further changes during reperfusion. METHODS: In part A of the study, rabbit femoral arteries were stored at 4 degrees C for up to 6 months. In part B rabbit femoral arteries were stored at 4 degrees C for up to 6 months, inserted as end-to-end autografts into contralateral femoral arteries, and reperfused for 24 hours. Tissue was examined by histologic study, transmission and scanning electron microscopy, histochemical study, immunohistochemical study, and tissue culture. RESULTS: Cell viability declined gradually at 4 degrees C, so that by 4 weeks no viable cells remained. However, the extracellular framework and elastic lamellae remain intact. If cold-stored arteries are reinserted as autografts for 24 hours, this accelerates breakdown of necrotic cells and reduces the thickness of the medial wall and internal elastic lamina but does not alter the extracellular framework. CONCLUSIONS: Cold storage results in acellular vascular grafts with intact extracellular frameworks. After 24 hours reperfusion there is no major change to the extracellular framework.

Actins↗
PubMed1995

Ambulatory medical detoxification for alcohol.

In the past decade, ambulatory medical detoxification for alcohol withdrawal has become increasingly utilized due to pressures to contain cost of treatment and research demonstrating its effectiveness. The research that describes this area spans the last 15 years. This article reviews the available literature on ambulatory detoxification and attempts to summarize and synthesize what is known about this area in order to make ambulatory medical detoxification readily reproducible in clinical practice. Finally, this article concludes with an analysis of the advantages and disadvantages of outpatient alcohol detoxification as compared to inpatient treatment.

Ambulatory Care↗
PubMed1994

Repair of congenital sternal clefts in adolescence and infancy.

Two cases of sternal cleft not associated with ectopia cordis are presented. An 11-year-old girl with a superior incomplete sternal cleft underwent reconstruction of the sternum with autologous rib, cartilage, and sternal periosteum. At the 1-year follow-up her sternal appearance was normal. The second patient, a full-term baby girl, had complete sternal cleft diagnosed by ultrasonography at 21 weeks' gestation. She underwent primary repair in the neonatal period and currently is asymptomatic with a normal-appearing sternum (10 months postoperatively). Primary repair in the neonatal period is the best type of management for this rare condition. For older patients, autologous repair is appropriate and avoids problems associated with the use of prosthetic materials.

Child↗
PubMed1994

Effect of route of administration and age on the pharmacokinetics of amikacin administered by the intravenous and intraosseous routes to 3 and 5-day-old foals.

The suitability of the intraosseous (i.o.) route for drug administration to equine neonates was evaluated in a study comparing the pharmacokinetics of amikacin administered by the i.o. and intravenous (i.v.) routes. Using a cross-over study design amikacin sulphate (7 mg/kg bwt) was administered i.o. or i.v. to 6 healthy foals at 3 and 5 days of age. Amikacin was instantaneously and completely absorbed after i.o. administration, achieving a mean +/- sd peak concentration (34.17 +/- 3.54 micrograms/ml) in the first sample collected 3 min after administration which was not significantly different from the mean +/- sd peak concentration (32.92 +/- 2.63 micrograms/ml) achieved after i.v. administration. The plasma amikacin concentration-time profiles for the i.o. and i.v. routes were not different and both were appropriately described by a 2-compartment open pharmacokinetic model. No significant differences attributable to route of administration were found in values for the major pharmacokinetic variables. The degree of inter-individual variation in values for indices of clearance was considerably greater than the degree of variation attributable to age. Despite this, values for body clearance (ClB) were significantly higher (P < 0.05) and values for area under the plasma amikacin concentration-time curve (AUC) and concentration of amikacin in plasma at 8 h [Cp(8h)] were significantly lower in 5- than in 3-day-old foals, indicating that amikacin was more rapidly cleared by the older foals. Technical difficulties were not encountered during i.o. needle placement in the medial aspect of the proximal tibia. Mild diffuse soft tissue swelling which developed at the i.o. site resolved completely within 1-2 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMedDate not supplied

Multiple transfusion fail to provoke antibodies against blood cell antigens in human infants.

We conducted studies of both red cell (RBC) and leukocyte (WBC) antibody formation in infants following multiple transfusions given during the first weeks of life. Fifty-three infants received 683 RBC transfusions from 503 different donors, plus 62 platelet, 4 granulocyte, and 53 fresh-frozen plasma units during the first 4 months of life. Three hundred fifty serum samples were obtained before, during, and after the transfusions. None of the infants formed unexpected RBC antibodies when tested at 37 degrees C by a two-cell low-ionic-strength solution antibody screen that included an anti-globulin phase. Twenty posttransfusion serums were negative when tested at room temperature. Lymphocytotoxic and granulocytotoxic WBC antibodies were measured in posttransfusion serums from 13 infants, and none were found. Despite exposure to many RBC and WBC antigens, no infants produced alloantibodies against blood cell antigens. Thus, immunologically mediated transfusion reactions should be quite rare in young infants, and this study supports recommendations of the American Association of Blood Banks Standards to omit repeat RBC compatibility testing during the first 4 months of life in infants whose initial RBC antibody screens reveal no unexpected antibodies.

Antibody Formation↗