Oral and subcutaneous sumatriptan in the acute treatment of migraine: an open randomized cress-over study

In an open, randomized cross-over study in 124 patients, we compared the efficacy, safety and patient preference of oral and subcutaneous sum triptan in the acute treatment of migraine. Patients were treated for 3 attacks or 3 months and then crossed over. Primary clinical efficacy was defined as a reduction in headache severity on a four-point self-rating scale from severe (3) or moderate (2) to mild (1) or none (0), or mild (1) to none (0). Efficacy was evaluated 2 h after the administration of subcutaneous and 4h after the administration of oral sumatriptan. Subcutaneous sumatriptan was significantly more effective than oral sumatriptan in relieving headache (over all three attacks 78% vs 61% improvement), improving clinical disability (55% vs 41 % improvement) and relieving nausea (69% vs 53%), vomiting (72% vs 32%) and phono- or photophobia (67% vs 49%). Median time to recurrence was shorter after subcutaneous (12.5 h) than after oral sumatriptan (18 h); the number of patients experiencing a recurrence was similar Patients reported more adverse events after subcutaneous sumatriptan (1.32 per attack) than after the oral form (0.85 per attack), but all adverse events were mild to moderate in intensity and of short duration. Patient opinion was more often positive after subcutaneous sumatriptan. These results may be useful in counselling patients to choose between the available marketed formulations of sumatriptan.     

Accelerating effects of epidermal growth factor on skin lesions of pemphigus vulgaris: a double-blind, randomized, controlled trial

BACKGROUND: Pemphigus vulgaris (PV) is a severe blistering disease involving the skin and mucous membranes. The most common causes of death in these patients are adverse effects of drugs, and infection. Skin lesions are one of the important sources of infection. Thus, any local treatment that could reduce healing time of lesions and consequently reduce the total dosage of drugs needed to treat is favourable. OBJECTIVE: To evaluate the efficacy of epidermal growth factor (EGF) in reducing healing time of lesions in patients with pemphigus vulgaris. METHODS: In this randomized, double-blind, within-patient, left/right, controlled trial, 20 hospitalized patients with pathologial and immunohistologial (direct and indirect immunoflourecence) proven pemphigus vulgaris (PV) were chosen. In addition, all patients had at least one appropriate pemphigus lesion on each side of the body that had not healed after 2-week systemic therapy and sterile saline washing. EGF (10 microg/g) in 0.1% silver sulfadiazine cream vs. 0.1% silver sulfadiazine cream alone was applied randomly on one side of the body. RESULTS: Kaplan-Meier survival analysis suggested that median time to heal with application of EGF plus silver sulfadiazine cream was 9 days, in comparison with 15 days for silver sulfadiazine cream alone (log-rank test, P=0.0003). No intervention-related adverse effect was observed during the study. CONCLUSIONS: EGF can significantly reduce healing time of skin lesions in patients with pemphigus vulgaris, at least when this cream base is applied (Cochrane skin group identifier: CSG20).     

Rapid prenatal diagnosis of sickle cell anemia by a new method of DNA analysis

We have used a new method of DNA analysis for the rapid prenatal diagnosis of sickle cell anemia in two fetuses at risk for this disease. This method of detecting the sickle gene is a modification of standard restriction-enzyme techniques and requires only a small amount of DNA. The first step involves a 200,000-fold enzymatic amplification of the specific beta-globin DNA sequences that may carry the sickle mutation. This provides a sufficient quantity of DNA for the analysis. Next, a short radiolabeled synthetic DNA sequence homologous to normal beta A-globin gene sequences is hybridized to the amplified target sequences. The hybrid "duplexes" are then digested sequentially with two restriction endonucleases. The presence of beta A- or beta S-globin gene sequences in the amplified target DNA from the patient determines whether the beta A-hybridization probe anneals perfectly or with a single nucleotide mismatch. This difference affects the restriction-enzyme digestion of the DNA and the size of the resulting radiolabeled digestion products, which can be distinguished by electrophoresis followed by autoradiography. This method is sufficiently sensitive and rapid that the prenatal diagnosis of sickle cell anemia can be made on the same day that the fetal DNA is made available. It can also be applied to the diagnosis of hemoglobin C disease.     

Effects of selective depletion of L3T4+ T-lymphocytes on herpes simplex virus encephalitis

The L3T4 surface molecule defines a subset of murine lymphocytes which are homologous to CD4+ lymphocytes in humans, and are functionally characterized as "helper/inducer" cells. To determine the role of helper/inducer lymphocytes in the host defense against herpes simplex virus type 1 (HSV-1) encephalitis, we utilized a monoclonal antibody to selectively deplete L3T4+ lymphocytes from BALB/c mice prior to experimental HSV infection. Susceptibility to HSV was only minimally increased by the depletion of L3T4+ cells, although mice receiving anti-L3T4 were profoundly immunosuppressed; splenic lymphocytes did not respond to stimulation by virus antigen in vitro, and L3T4+ lymphocyte-depleted mice failed to produce antibodies to HSV-1. However, mice receiving anti-L3T4 had a prolonged increase in natural killer cell activity following HSV infection as compared to controls. These data demonstrate that L3T4+ lymphocytes contribute minimally to host resistance to acute neural HSV infection, even though elimination of these lymphocytes markedly inhibits the genesis of immune responses.     

Principles and applications of the polymerase chain reaction

The polymerase chain reaction (PCR), a primer-directed in vitro enzymatic reaction for the production of a specific DNA fragment, has dramatically facilitated molecular biology approaches to fundamental research questions, as well introduced DNA testing into a variety of clinical diagnostic areas. Some of the principles of PCR, several recent advances in PCR technology and selected applications are reviewed. A variety of methods for analyzing allelic sequence diversity in amplified DNA have been developed. Genetic testing of the HLA loci, and other genes encoding cytokines and cytokine receptors, has had a significant impact on disease susceptibility studies and in clinical transplantation.     

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.