Dr. Solco Tromp and the Tromp Award.

The Tromp Award is the highest honor awarded by the International Society of Biometeorology (ISB). The award acknowledges outstanding research in biometeorology by a scientist under the age of 35 and was established in conjunction with the Tromp Foundation and the ISB. In honor of the 60th anniversary of the ISB, this article will provide a brief summary of the life of Dr. Solco Tromp and of the six awardees of the Tromp Award since the inaugural issuance of the award in 1999. The Tromp Award was established in part to recognize and support the efforts of young biometeorological professionals. As the brief summary of the awardees and a few of their selected subsequent publications have shown, the ISB and the Tromp Award has proven effective at identifying and supporting promising young scientists.

A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities.

The purpose of this study was to determine the efficacy of controlled-release (CR) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders. A randomized double-blind, placebo-controlled crossover trial of CR melatonin (5 mg) followed by a 3-month open-label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects. Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs. Clinician rating of severity of the sleep disorder and improvement from baseline, along with caregiver ratings of global functioning and family stress were also obtained. Fifty-one children (age range 2-18 years) who did not respond to sleep hygiene intervention were enrolled. Fifty patients completed the crossover trial and 47 completed the open-label phase. Recordings of total night-time sleep and sleep latency showed significant improvement of approximately 30 min. Similarly, significant improvement was observed in clinician and parent ratings. There was additional improvement in the open-label somnolog measures of sleep efficiency and the longest sleep episode in the open-label phase. Overall, the therapy improved the sleep of 47 children and was effective in reducing family stress. Children with neurodevelopmental disabilities, who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance, showed improvement in melatonin therapy.

Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders.

To date, there have been no prospective long-term studies of melatonin therapy in children. We report here data from a prospective follow-up study of 44 children with neurodevelopmental disabilities and treatment-resistant circadian rhythm sleep disorders (CRSD) who had participated in a placebo controlled, double blind cross-over trial of sustained-release melatonin. The follow-up study involved a structured telephone interview of caregivers every 3 months for upto 3.8 yr. The caregivers provided ratings of satisfaction, adverse effects, benefits, persistence with treatment and additional medications. Changes in melatonin dose were recorded. Open ended questions were included to capture caregivers' impressions and comments concerning melatonin therapy. Adverse reaction to melatonin therapy and development of tolerance were not evident. Better sleep was associated with reported improvement in health, behavior and learning. At the end of the study, the parental comments regarding the effectiveness of long-term melatonin therapy were highly positive. Parents whose children had sleep maintenance difficulties expressed a wish to have a commercially available controlled-release melatonin product which would promote sleep for 8-10 hr. Hypnotics for children with CRSD should be considered a second line of treatment for those who fail to respond to sleep hygiene and/or melatonin.

Sun exposure, sexual behavior and uterine cervical human papilloma virus.

We have previously observed marked seasonal fluctuations in the frequency of cervical smears positive for human papilloma virus (HPV) in a series of smears obtained in Holland, with a peak in the summer months, especially August. Here, we tested two possible mechanisms that might underlie this summer peak: (1) enhanced transmission of HPV due to increased seasonal sexual activity, or (2) suppression of immunity due to summertime population exposure to solar ultraviolet (UV) radiation. Data derived from a continuous series of >900,000 independent cervical smears obtained from 1983 to 1998 were assessed for histopathologic epithelial changes pathognomonic of HPV. The rate of HPV positivity was then compared to both the rate of sexual activity (using conception frequency as a readily available surrogate) as well as yearly and monthly fluctuations in solar-UV fluency. The rate of HPV positivity was found to be twice as high during the summer months, with a peak in August corresponding with maximal UV fluency. Furthermore, over these 16 consecutive years of continuous observation, maximum HPV detection rate and maximum UV fluency are positively correlated (r=0.59, P<0.01); the sunnier the year, the greater the rate of HPV. Likewise, there is a positive correlation of the monthly UV fluency, and monthly HPV discovery rate (r=0.16, P<0.03). In contrast, conception frequency (and, presumably, population sexual HPV transmission) was maximal near the vernal equinox, with relatively modest (<10%) seasonal fluctuation, i.e., not fully explaining this prominent August peak in HPV discovery. There is a clear relationship between the detection of HPV-positive cervical smears and sunlight exposure. We speculate that the well-known phenomenon of UV-mediated suppression of immune surveillance may be causally related to this unusual increase in cytologically defined active HPV infections during the summer months in northern countries such as Holland. Confirming this relationship elsewhere may be important, because whatever the risk conferred by sunlight is, in principle, behaviorally avoidable.

Season, sun, sex, and cervical cancer.

INTRODUCTION: Sunlight's UV B component, a known cellular immunosupressant, carcinogen, and activator of viral infections, is generally seasonally available. Venereal human papillomavirus (HPV) transmission, at least in part, causes cervical cancer. We have previously inspected the monthly rates of venereal HPV infection and sunlight fluency in Southern Holland over 16 consecutive years. Both peak in August with at least 2-fold seasonality. The amount of available sunlight and the rate of Papanicolaou (Pap) smear screen-detected HPV are positively correlated. We now investigate whether premalignant and malignant cervical epithelial changes are also seasonal and related to seasonal sunlight fluency. METHODS: We have studied >900,000 consecutive, serially independent, interpretable screening Pap smears obtained by a single cervical cancer screening laboratory in Leiden, Holland, during a continuous 16-year span from 1983 through 1998. The average monthly rates of premalignant and malignant epithelial change were inspected and the annual patterns contrasted to the annual pattern of sunlight fluency at this global location and to monthly average HPV infection rate. Because HPV is venereally transmitted, Dutch seasonal sexual behavior was evaluated by assessment of the annual pattern of Dutch conception frequency as a competing cause for cervical cancer seasonality. RESULTS: (a) Twice as many premalignant and malignant epithelial changes were found among Pap smears obtained in the summer months, with an August peak concurrent with histopathologic evidence of HPV infection and sunlight fluency in Southern Holland. (b) Monthly sunlight fluency is correlated positively with both the monthly rates of Pap smear-detected cervical epithelial dysplasia and carcinomatous histopathology, as well as HPV. (c) Conception frequency, in this location, peaks in Spring not summer, and has a 4.8% annual amplitude. CONCLUSIONS: (a) Cervical epithelial HPV infection and HPV-induced cervical epithelial dysplasia and carcinomatous change may each be novel sun exposure risks and thereby behaviorably avoidable. (b) Because screening Pap smears uncover many abnormalities that resolve spontaneously (false positives), these data may argue for screening and follow-up Pap smear examinations in seasons other than summer in the Northern Hemisphere, to diminish the false-positive smear rate. Global data are available to confirm and further test each of these conclusions.