Roblee Allen | PubMed Health

PubMed2005

Pharmacokinetics and clinical effects of mono-L-aspartyl chlorin e6 (NPe6) photodynamic therapy in adult patients with primary or secondary cancer of the skin and mucosal surfaces.

BACKGROUND/PURPOSE: Mono-L-aspartyl chlorin e6 (NPe6) is a photosensitizer that exhibits chemical purity, absorption at 664 nm wavelength and may be useful in photodynamic therapy (PDT). METHODS: This open label phase I clinical trial at the University of California, Davis Medical Center examined the pharmacokinetic properties of Npe6 and clinical response to PDT with this photosensitizer. A single intravenous dose of Npe6 was administered to 14 cancer patients with superficial malignancies (basal cell carcinoma = 22 lesions, squamous cell cancer = 13 lesions, papillary carcinoma = 14 lesions). Patients received one of five ascending doses (0.5 mg/kg (n = 4), 1.0 mg/kg (n = 3), 1.65 mg/kg (n = 3), 2.5 mg/kg (n = 3), or 3.5 mg/kg (n = 1)) 4-8 h prior to light activation. The total light dose (range 25-200 J/cm2) depended on the tumor shape and size. Light was delivered using an argon-pumped tunable dye laser. Serum NPe6 concentrations were measured over a 28-day period. The toxicity and cutaneous clinical efficacy of NPe6 were observed. RESULTS: Four weeks post-PDT, 20 of 22 basal cell carcinoma tumors (91%) showed a complete response. Eighteen of 27 other malignant cutaneous tumors showed a complete (n = 15/27, 56%) or partial (n = 3/27, 11%) response. Fewer non-responders were seen at an Npe6 dose level of 1.65 mg/kg or higher. Only 2 of 14 patients experienced an adverse event that was definitely related to NPe6 administration. Photosensitivity resolved within 1 week of NPe6 dosing in 12 of 14 patients. Analysis of serum levels of 11 individual patients indicated that a two-compartment model with a residual phase best fits the data. The mean alpha, beta, and terminal half-lives were 8.63+/-2.92, 105.90+/-37.59 and 168.11+/-53.40 h (+/-1 SD), respectively. The observed mean volume of distribution was 5.94+/-2.55 l, and the mean clearance was 0.0394+/-0.0132 l/h. These values were independent of the dose administered. CONCLUSION: The photosensitizer, NPe6, was well tolerated with minimal phototoxic side effects, and demonstrated preliminary efficacy against cutaneous malignancies.

Aged↗

PubMed2004

Bronchiolitis obliterans: an update.

PURPOSE OF REVIEW: Bronchiolitis obliterans (BO) occurs in both post-lung transplant and nontransplant-related individuals, and is characterized by mainly irreversible airflow obstruction that is often ultimately progressive. RECENT FINDINGS: While post-lung transplant BO is a major cause of lung allograft dysfunction, and hence is better characterized than nontransplant-related BO, it is likely that many similarities in pathogenesis and treatment apply to both categories. SUMMARY: Optimal management for BO remains to be established, and the role of retransplantation in this disease requires further consensus. Minimization of risk factors for BO and earlier detection in the form of methacholine challenge testing and HRCT scans of the chest amongst other forms of detection, may help in the stabilization and possible resolution of early BO.

Biopsy↗

PubMed2004

Epoprostenol in pregnant patients with secondary pulmonary hypertension: two case reports and a review of the literature.

Women who present with pulmonary hypertension during gestation have traditionally been persuaded to terminate their pregnancy. Historically, the mortality associated with this group is very high. Certain patients with a secondary cause of pulmonary hypertension are believed to share similar pathophysiology with primary pulmonary hypertension patients. Recently, new treatments have become available that have slowed disease progression. We present the successful treatment of two patients who presented during late gestation with moderate pulmonary hypertension. Both patients were managed with intravenous vasodilators and anticoagulants without complication. Each patient successfully delivered a healthy child via spontaneous vaginal delivery. The review of the historical management of similar patients including new insights into the etiology of pulmonary arterial hypertension is also included. It highlights the complexity involved in managing such patients and the requirement of a multidisiplinary team approach.

Adult↗