A Guide to Immunotherapy of Genital Warts

Genital warts affect at least 1% of sexually active adults. Current therapies are inadequate because they are often painful, may fail to prevent recurrence and transmission of warts, and usually require either surgery or at least application by a physician. Investigation of immunotherapy for genital warts began with interferon. It has been studied in topical, intralesional, systemic and adjuvant applications. We review the major clinical trials of interferon for genital warts, and conclude that intralesional therapy with interferon-alpha or interferon-beta, with complete response rates of 36 to 63%, is the most successful route for interferon monotherapy. In choosing patients for therapy with interferon, major considerations include immune status, pregnancy and ability to return for frequent injections. Imiquimod is a new immune response enhancer that acts through stimulating host cytokine production. Interleukins-1, -2, -6, -8 and -12, interferons alpha, beta and gamma and tumour necrosis factor alpha have all been associated with the mechanism of action of imiquimod. Recently, 3 clinical trials have reported positive results using topical imiquimod to treat genital warts. Complete response rates ranged from 37 to 54% for these controlled trials of 5% imiquimod cream. Adverse effects reported include localised pruritis, erythema, erosion, burning and pain, which were rarely severe enough to cause discontinuation of the medication. Although further trials are necessary to identify the role of imiquimod in the therapy of genital warts, it appears to be an efficacious and well tolerated patient-controlled measure for wart therapy.     

The effect of lesions of the sensorimotor cortex and the capsular pathways on servo responses from the human long thumb flexor

Lesions of the sensorimotor cortex, or of the capsular pathways beneath it, caused (with one exception out of 14 cases) diminution "r loss of the servo responses in the thumb, which are based on the long-latency stretch reflex. When not absent the long-latency stretch reflex tended to be late in onset. When absent it was often replaced by a large early reflex response at spinal latency. In general the results are consistent with the transcortical theory of the long-latency stretch reflex for the thumb, but, in detail, they indicate that the theory will require elaboration.     

Anticonvulsant and proconvulsant properties of viloxazine hydrochloride: Pharmacological and pharmacokinetic studies in rodents and the epileptic baboon

Viloxazine HCl is evaluated as an anticonvulsant in a wide range of rodent seizure models and in the epileptic baboon (Papio papio). In the maximal electroshock test, the oral ED₅₀ for abolition of tonic extension was 9 mg/kg^-1 after 30-min pretreatment (mouse) rising to 30 mg/kg^-1 after 60 min (mouse and rat). Comparable ED₅₀ values were also found for protection against tonic extension in the mouse induced by the administration of the chemical convulsants metrazole or 3-mercaptopropionic acid. In DBA/2 mice the ED₅₀ for abolition of tonic extension during sound-induced seizures was 6.8 mg/kg^-1 IP (30-min pretreatment). Pharmacokinetic studies in the mouse showed peak plasma levels to occur 30 min following oral doses, with a mean half-life of 58 min. The anticonvulsant plasma concentration was within 0.5–1 g/ml^-1. In the baboon, significant protection against photomyoclonic responses is observed 1–2 h after viloxazine (2.6 mg/kg^-1 IV), during which period the plasma concentration was again 0.5–1 g/ml^-1. After administration of approximately ten-times this latter dose level, i.e. 24 mg/kg^-1 IV, a syndrome characterised by an abnormal EEG and, in some instances, seizure activity was observed.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

Serum protein profiles to identify head and neck cancer.

PURPOSE: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. The purpose of this study was to determine whether a new proteomic technology could correctly identify protein expression profiles for cancer in patient serum samples. EXPERIMENTAL DESIGN: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ProteinChip system was used to screen for differentially expressed proteins in serum from 99 patients with HNSCC and 102 normal controls. Protein peak clustering and classification analyses of the surface-enhanced laser desorption/ionization spectral data were performed using the Biomarker Wizard and Biomarker Patterns software (version 3.0), respectively (Ciphergen Biosystems, Fremont, CA). RESULTS: Several proteins, with masses ranging from 2778 to 20800 Da, were differentially expressed between HNSCC and the healthy controls. The serum protein expression profiles were used to develop and train a classification and regression tree algorithm, which reliably achieved a sensitivity of 83.3% and a specificity of 100% in discriminating HNSCC from normal controls. CONCLUSIONS: We propose that this technique has potential for the development of a screening test for the detection of HNSCC.     

Is there an incremental rise in the risk of obstetric intervention with increasing maternal age?

Objective To determine whether increasing maternal age increases the risk of operative delivery and to investigate whether such a trend is due to fetal or maternal factors.
Design Analysis of prospectively collected data on a maternity unit database.
Setting A postgraduate teaching hospital.
Population 6410 nulliparous women with singleton cephalic pregnancies delivering at term (37–42) weeks of gestation) between 1 January 92 and 31 December 95.
Main outcome measures Mode of delivery, rates of prelabour caesarean section, induction of labour and epidural usage.
Results There was a positive, highly significant association between increasing maternal age and obstetric intervention. Prelabour (  P < 0.001  ) and emergency (   P < 0.001  ) caesarean section, instrumental vaginal delivery (spontaneous labour   P < 0.001  ; induced labour   P = 0.001  ), induction of labour (   P < 0.001  ) and epidural usage in spontaneous labour (  P = 0.005  ) all increased with increasing age. In the second stage of labour fetal distress and failure to advance, requiring instrumental delivery, were both more likely with increasing maternal age (in both   P < 0.001  ). Epidural usage in induced labour and the incidence of small for gestational age newborns did not increase with increasing maternal age (P = 0.68 and  P = 0.50  , respectively).
Conclusions This study demonstrates that increasing maternal age is associated with an incremental increase in obstetric intervention. Previous studies have demonstrated a significant effect in women older than 35 years of age, but these data show changes on a continuum from teenage years. This finding may reflect a progressive, age-related deterioration in myometrial function.