Photodynamic therapy using aminolaevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: phase IV multicentre clinical trial with 12-month follow up.

BACKGROUND: Actinic keratoses (AKs) are the most common epithelial precancerous lesions, especially among individuals with light complexions. AKs are believed to progress to in situ squamous cell carcinoma (SCC) and potentially, to invasive SCC. AKs and invasive SCCs share certain histopathological features and both share genetic tumour markers and p53 mutations. Given these facts, the treatment and management of AKs are integral components to quality dermatological health care. OBJECTIVES: Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been extensively studied over the last several years. This study seeks to characterize further the efficacy and safety of ALA-PDT by extending previous work to: (i) assess the long-term recurrence rate of AKs that have resolved after ALA-PDT; (ii) to characterize the histopathology of treated AK lesions that do not completely respond to ALA-PDT or recur in long-term follow up; (iii) to characterize the histopathology of untreated clinically diagnosed AK lesions in the study population at baseline; and (iv) to evaluate ALA-PDT in darker skin types than previously studied. METHODS: Patients enrolled in this study had six to 12 discrete AK lesions, either on the face or the scalp. Individual AK lesions designated for treatment were graded as either grade 1 (lesions slightly palpable and more easily felt than seen) or grade 2 (moderately thick AKs, easily seen and felt). Patients with grade 3 (very thick and/or hyperkeratotic) lesions were excluded. For each subject, two lesions at baseline were randomized to biopsy, and were not followed as part of the study while the remaining lesions (target lesions) were treated with ALA-PDT (baseline and month 2, if required) and followed for 12 months. RESULTS: Of the 110 patients enrolled, 101 completed the study. The target AK lesions in the per-protocol population clearing completely in the first and second months following a single ALA-PDT treatment (baseline) were 76% and 72%, respectively. Sixty per cent of the patients received a second ALA-PDT treatment, limited to the target AKs still present at month 2. The percentage of treated target lesions that cleared completely peaked at 86% at month 4 then decreased gradually over time to 78% at month 12. The overall recurrence rate for all lesions that were noted to be cleared at some visit during the 12-month period was 24% (162/688). Of the 162 recurrent lesions 16 were lost to follow up, seven spontaneously cleared and 139 were biopsied. With respect to the lesions biopsied, 91% (127/139) were diagnosed histopathologically as AK, with the balance of lesions being SCC (nine of 139: 7%), basal cell carcinoma (one of 139: 0.7%) and other non-AK diagnoses (two of 139: 1%). The recurrence rate for histologically confirmed AKs was 19%. The clinical diagnosis of AK by investigators appeared to be accurate, with 91% (200/220) of the untreated clinically diagnosed AK lesions being histopathologically confirmed to be AK (AK, 142/220: 65%; advanced AK, 29/220: 13%; macular AK, 29/220: 13%). Despite concentrated efforts to recruit patients with Fitzpatrick skin types IV-VI, the distribution was as follows: I, 11%; II, 36%; III, 41%; IV, 11%; V, 2%. The demographics of this study population are typical of a patient population with AK. CONCLUSIONS: ALA-PDT was shown to be an effective and safe therapy for the treatment of AKs of the face and scalp in skin types I-V, with an acceptable rate of recurrence over 12 months of histologically confirmed AKs of 19%. Phototoxicity reactions were all expected, nonserious and had essentially resolved after 1 month post-treatment independent of skin type.

Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. The Peptide T Neuropathy Study Group.

OBJECTIVE: To assess the safety and efficacy of Peptide T in the treatment of painful distal symmetrical polyneuropathy (DSP) associated with human immunodeficiency virus (HIV) infection. BACKGROUND: Painful DSP is a frequent complication of HIV infection, although its etiology and optimal treatment are unknown. Peptide T (D-(alpha 1)-Peptide T-amide) has been found in phase I trials and anecdotal reports to relieve neuropathic pain in AIDS patients. DESIGN/METHODS: In this multicentered, double-blind, randomized study, subjects received intranasal Peptide T 6 mg/day or placebo for 12 weeks. The primary outcome measure was change in the modified Gracely pain score. Secondary efficacy variables were results of neurologic examination, neuropsychological and electrophysiologic studies, global evaluation, and CD4 lymphocyte counts. RESULTS: Of 81 evaluable subjects, 40 received Peptide T and 41 received placebo. The change in pain scores was not significantly different (p = 0.32) in the Peptide T group (-0.24) as compared to placebo (-0.39). Group comparisons were not significantly different for change in any clinical examination or neuropsychologic measure, sural nerve amplitude or conduction velocity, or CD4 lymphocyte count. No significant drug-related adverse effects occurred in either group. CONCLUSION: Intranasal Peptide T is safe but ineffective in the treatment of painful DSP associated with AIDS.

Systemic and local immune responses to enhanced-potency inactivated poliovirus vaccine in premature and term infants.

Serum neutralizing, nasopharyngeal neutralizing, and IgA antibodies to polioviruses 1, 2, and 3 were detected in preterm and term infants who had received three doses of an enhanced-potency inactivated poliovirus vaccine at 2, 4, and 12 months of age. After the third dose of this vaccine, 95% or more of the infants tested had detectable serum neutralizing antibodies to polioviruses types 1, 2, and 3. Nasopharyngeal neutralizing and IgA antibodies were detected in 43% to 91% of the infants. The peak geometric mean titers of serum and nasopharyngeal antibodies against polioviruses types 1, 2, and 3 were similar for both groups. These preliminary data indicate that preterm infants are capable of mounting systemic and local immune responses to enhanced-potency inactivated poliovirus vaccine that are comparable to those made by term infants.

Comparative evaluation of immunization with live attenuated and enhanced-potency inactivated trivalent poliovirus vaccines in childhood: systemic and local immune responses.

Serum neutralizing, nasopharyngeal neutralizing, and IgA antibodies were determined in 123 infants immunized with one of four schedules containing live oral vaccine (OPV), inactivated vaccine (IPV), or combinations of the two trivalent poliovirus vaccines: OPV-OPV-OPV, IPV-IPV-IPV, IPV-OPV-OPV, or IPV-IPV-OPV. Nearly 100% of individuals formed serum neutralizing antibodies. The highest geometric mean titer (GMT) of antibody to polioviruses 1, 2, and 3 occurred in groups IPV-IPV-OPV, IPV-OPV-OPV, and IPV-IPV-IPV, respectively. Local neutralizing and IgA antibody responses were detected in 41%-88% and 75%-100%, respectively. Peak GMT of nasopharyngeal antibodies differed minimally between immunization groups. The data suggest that incorporation of at least one dose of IPV at the start of the immunization schedule tends to increase systemic as well as local antibody production.

Electromyographic feedback: effects on voluntary muscle contractions in normal subjects.

To evaluate the efficacy and function of EMG feedback (FB) in muscle reeducation, voluntary muscle contractions with and without EMG FB were compared under controlled experimental conditions in normal human subjects (n=10). Each subject was instructed to produce 12 sustained, 30-second contractions of the left abductor hallucis muscle, 6 contractions in each of 2 sessions. For all subjects, EMG FB was provided in half of the trials, alternating with nonfeedback (NFB) trials. A ranking task was included to measure ability to discriminate contractions in the target muscle. EMG activity was significantly greater during muscle contractions attempted with EMG FB; this was due to increased motor unit recruitment early in the course of the trials, a positive response in normal subjects similar to that in paretic subjects in our previous study. Performance on the ranking task also indicated that subjects had little perceptual awareness of their muscle contractions. Our findings suggest that the positive response to EMG FB was due to the precise information it provided concerning small, poorly discriminated muscle contractions.