The importance of accurate dosage of topical agents: a method of estimating involved area and application to calcipotriol treatment failures

Little attention is given to accurate dosage of topical medication which is a potential source of side-effects and treatment failure. There are studies on the dosage for 'sparing' application relevant to topical steroids but not for 'liberal' application. Though calcipotriol is a first line topical treatment for psoriasis, approximately one-third of patients do not respond adequately. The aims of the present study were to define liberal dosage, to develop a method of calculation of area of involved skin and to evaluate the efficacy of calcipotriol in optimized liberal dosages, based on preliminary studies, in calcipotriol treatment failures. Weight/unit area of ointment and cream base, constituting liberal application, was determined in six normal volunteers. The area of psoriatic involvement in 24 calcipotriol non-responders was estimated by a 'fill-up' method and a modified 'hand' method. The results of the two methods were similar (Pearson correlation coefficient 0.68, P < 0.0001) but the 'hand' method proved easier in use and was the preferred method for the rest of the study. The patients applied calcipotriol at their accustomed rates for at least 2 weeks and then at the calculated liberal rates, using cream in the morning and ointment at night, for 4 weeks. The efficacy measures were Psoriasis Area and Severity Index (PASI) (primary measure), a four-point efficacy score and a visual analogue scale. As a result of the preliminary study and the actual amounts used by the patients in the psoriasis treatment study reported below, liberal application has been defined as 50 g/m2 per application for ointment base and 40 g/m2 per application for cream. At this dosage, an average individual would use approximately 100 g of medication/week to treat 10% of the body surface. During the 4-week treatment study, the psoriasis patients used an average of 39 g (SD 17 g)/m2 per application of cream and 52 g (SD 13 g)/m2 per application of ointment. All efficacy measures showed marked improvement (P < 0.0001). The frequency distribution of the PASI reduction defined responsive (70% of patients) and poorly responsive groups (30%), with mean PASI reduction of 60% and 17%, respectively.     

Stimulation of human cytotoxic T cells with HIV-1-derived peptides presented by recombinant HLA-A2 peptide complexes

HLA-A2 heavy chain and beta 2-microglobulin were expressed in Escherichia coli, and refolded in the presence of peptides derived from HIV-1 RT and gag proteins. When recombinant HLA-A2 molecules were attached to cells lacking HLA-A2, the cells became susceptible to lysis by HLA-A2-restricted cytotoxic T lymphocyte (CTL) clones specific for peptides derived from RT and gag proteins. Limiting dilution analyses of peripheral blood mononuclear cells from HIV-1-infected individuals showed that the recombinant HLA-A2 peptide complexes covalently immobilized on microspheres stimulated the development of HLA-A2 peptide-specific CTL. Preformed HLA-peptide complexes may provide an alternative to immunization procedures that depend upon intracellular processing of antigen to elicit T cell responses.      

Optimization of Thermocautery in Excisional Dermatologic Surgery

PURPOSE: Electrosurgery is routinely used in cutaneous surgery for hemostasis. Thermocautery can be used in patients with implantable cardiac devices. This technique relies on heat without electrical current passing through the patient to produce hemostasis. The temperatures and utility of a commercially available, adjustable thermocautery unit are examined. METHODOLOGY: Tip temperature of the commercially available thermocautery unit was measured in air and tissue via a type E thermocouple (0.002 in. diameter) around the unit's tip. Time intervals of 20 to 30 seconds were recorded at device settings 1 to 9 in air and 3 to 8 on surgical patients (Institutional Review Board approval obtained). RESULTS: In vitro analysis demonstrated predictable temperatures at increasing settings in air: 350 to 900 degrees C. Analysis in vivo during surgery demonstrated similar findings. Tissue contact decreased tip temperature by approximately 50% from in vitro values, and use in a bloody field caused a further decrease in the tip temperature. CONCLUSION: The thermocautery unit examined is an effective and safe unit to achieve hemostasis. In addition, the temperature may be adjusted as opposed to hand-held units that operate at in vitro temperatures exceeding 1,400 degrees F. Hemostasis at approximately 100 to 400 degrees C provided optimal hemostasis.     

An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene

The gene for autosomal recessive spinal muscular atrophy (SMA) has been mapped to 5q12 in a region that contains repeated markers and genes. Three cDNAs that detect deletions in SMA patients have been reported. One of these, the survival motor neuron (SMN) cDNA, is encoded by two genes (SMNT and SMNC) which are distinguished by base changes in exons 7 and 8. Exon 7 of the SMNT gene is not detectable in approximately 95% of SMA cases, due either to deletion or sequence conversion. There is limited information on the mutations in SMA patients that have detectable SMNT, these are critical for confirmation of SMNT as the SMA gene. Using SSCP analysis of the SMN exons we screened our SMA patients that possess at least one intact SMNT allele for mutations in SMNT. We identified one type I SMA patient with an 11 bp duplication in exon 6 which causes a frameshift and premature termination of the deduced SMNT protein. Dosage and SSCP analysis of SMNT in this family indicated that the father contributed a SMNT-deleted allele to the affected child whereas the mother passed on the 11 bp exon 6 duplication SMNT allele. Analysis of RNA by RT-PCR conclusively demonstrated that the 11 bp duplication is associated with the SMNT locus and not SMNC. This mutation provides strong support for SMN as the SMA-determining gene and indicates that disruption of SMNT on its own is sufficient to produce a severe type I SMA phenotype.      

Ultrasound appearances in de Quervain's subacute thyroiditis with long-term follow-up.

In order to determine whether permanent echo abnormalities are produced by subacute thyroiditis, ultrasound examination of the thyroid was performed repeatedly after a mean interval of 23 months in 17 subjects (8 women and 9 men) aged 31-52 (mean 41) years, suffering from subacute thyroiditis. The diagnosis was based on typical clinical symptoms, and cytological confirmation was obtained in all subjects but one. In the primary phase the ultrasonic finding was in all cases abnormal, showing either diffuse or focal hypoechogenicity and enlargement of thyroid lobes. At follow-up, a homogenous echo structure was found in 15 patients. Nodularity was detected in only two subjects. It is concluded that permanent focal echo abnormalities are generally not produced by subacute thyroiditis. Consequently, thyroid nodules in subjects with a history of SAT should not be ignored.     

Heterogeneity of autosomal dominant osteopetrosis

A review of the radiographs of 26 patients with autosomal dominant osteopetrosis disclosed two distinct and strictly family-related radiographic types. Both types had universal osteosclerosis. In type 1 the most striking finding was pronounced sclerosis of the cranial vault while the spine was almost unaffected. In type 2 the sclerosis of the skull was most pronounced at the base, the vertebrae always had end-plate thickening, and in the pelvis the iliac wings contained convex arcs of sclerotic bone. Age and sex distribution did not differ between the types. Autosomal dominant osteopetrosis may be a heterogeneous group of inherited bone disorders.     

Nocturnal oxygen saturation and body movement in asthmatics treated with controlled-release preparations of theophylline or terbutaline

Summary Nine adult asthmatics with a history of nocturnal symptoms and with morning dips in peak expiratory flow (PEF) were treated for 10–14 days with 24-h controlled-release preparation of theophylline (Th), or a controlled-release preparation of terbutaline (Te), in a double-blind cross-over experiment.During treatment with 450–900 mg Th in the evening morning, plasma drug levels ranged from 53–95 (mean 73) mol/l. The Te dose was 7.5 mg twice daily. Morning PEF values during Th (mean 338 l·min^–1) and Te (316 l·min^–1) were not significantly different. There were no significant differences between the treatments in average nocturnal oximetric O₂ saturation (91.9% during Th and 91.0% during Te), or the amount of nocturnal body movement, recorded with a static charge sensitive bed (total number of movements 146 during Th and 120 during Te).No difference between the treatments was seen with respect to assessment by the subjects of sleep quality, which was considered fair or good.The findings suggest that in moderately severe asthma, nocturnal oxygenation and sleep quality were similar during the two treatments.     

Mechanism of human accommodation as analyzed by nonlinear finite element analysis

Results of nonlinear finite element analysis support the Schachar theory of accommodation and demonstrate that the long-held Helmholtz theory of accommodation is impossible.