SQUAMOUS CELL CARCINOMA IN KAUAI, HAWAII

Background. It is estimated that over 100,000 new cases of squamous cell carcinoma are diagnosed in the United States annually. This number is compounded by an increasing concern over the ozone layer depletion and the continued sunbathing behavior of many individuals. This could be particularly acute in Hawaii, which may have the highest rates of skin cancer in the country. We believe the updated information on skin cancer is essential to address the magnitude of the problem. Methods. A prospective 5-year population-based incidence study was conducted on Kauai, Hawaii, between 1983 and 1987 to investigate the frequency of squamous cell carcinomas in resident Caucasians. Results. A total of 58 residents, 37 men and 21 women, were identified with an initial episode of squamous cell carcinoma during the 5-year period. The average annual incidence rate per 100,000 Kauai Caucasian residents, standardized to the 1980 U.S. white population, was 153 for men and 92 for women with a combined rate of 118. The average patient age was 66.4 years. The head and neck was the most common anatomic site, with the extremities second. Subsequent new squamous cell carcinoma occurred in 13.8% of patients. Only one patient (2%) developed a recurrence after treatment. Twenty-five patients (43%) had basal cell carcinoma simultaneously or at other earlier times. Conclusions. In Kauai the incidence rate of squamous cell carcinoma is the highest yet documented in the United States. No consistent trend in incidence rates was appreciated during this 5-year period.     

A Subset of Patients With Recurrent Spontaneous Abortion Is Deficient in Transforming Growth Factor β-2-Producing “Suppressor Cells” in Uterine Tissue Near the Placental Attachment Site

PROBLEM : To determine if patients with unexplained recurrent miscarriage have a deficiency of decidual immunosuppressor cells that produce transforming growth factor β type 2, as has been found in mice with abortion due to rejection and/or trophoblast failure. METHODS : Decidual biopsy specimens were taken as near to the placental attachment site as possible under ultrasound guidance from first trimester legal termination (control) patients with recurrent miscarriage and non-viable pregnancy, and from patients with sporadic missed abortion. The tissue was tested for TGFβ-2⁺ suppressor cells by in situ hybridization, immunohistochemistry, and analysis of supernatants. RESULTS : TGFβ-2-related suppressor molecules similar but not identical to those identified in pregnant mice were released by decidual lymphoid cells. Fifty percent of 14 recurrent miscarriage patients showed a lack of suppressor cells and 59% were subnormal in comparison to 20 controls and 5 sporadic miscarriage patients, where 80–85% of the patients had detectable suppressor cells. CONCLUSIONS : Suppressor cell deficiency is compatible with a role for rejection and/or trophoblast failure in some patients with recurrent miscarriage. Presence of suppressor cells in most patients with missed abortion (4/5) is compatible with an alternative cause of fetal death, similar to findings reported in genetic fetal death mice.     

Intellectual disability: population‐based estimates of the proportion attributable to maternal alcohol use disorder during pregnancy

Aim The aim of this study was to examine the association between maternal alcohol use disorder and intellectual disability in children. Method All mothers with an International Classification of Diseases (ICD) 9 and/or 10 alcohol‐related diagnosis, a proxy for alcohol use disorder, recorded on the Western Australian health, mental health, and drug and alcohol data sets were identified through the Western Australian Data Linkage Unit (n=5614 non‐Aboriginal; n=2912 Aboriginal). A comparison cohort of mothers without an alcohol‐related diagnosis was frequency matched on maternal age within maternal Aboriginal status and year of birth of their children. Linkage with the Western Australian Midwives Notification System (1983–2001) identified all births to these mothers (n=10 664 and 7907 respectively). Linkage to the Western Australian Intellectual Disability Database and Register of Developmental Anomalies identified cases of intellectual disability with no identified genetic origin (intellectual disability) (n=1487) and fetal alcohol syndrome (n=66). Odds ratios (ORs) and 95% confidence intervals (CIs) for intellectual disability were calculated using logistic regression incorporating generalized estimating equations and used to estimate population‐attributable fractions. Results At least 3.8% (95% CI 2.84–4.89%) of cases of intellectual disability could be avoided by preventing maternal alcohol use disorder: 1.3% (95% CI 0.81–1.86%) in non‐Aboriginal and 15.6% (95% CI 10.85–20.94%) in Aboriginal children. We observed a three‐fold increase in the adjusted odds of intellectual disability in children of mothers with an alcohol‐related diagnosis recorded during pregnancy (non‐Aboriginal OR 2.89, 95% CI 1.62–5.18; Aboriginal OR 3.12, 95% CI 2.13–4.56), with a net excess proportion of 3.7% and 5.5% respectively. One‐third (32%) of children diagnosed with fetal alcohol syndrome had intellectual disability. Interpretation Maternal alcohol use disorder is the leading known risk factor for intellectual disability with no identified genetic origin.     

CHANGES IN THE PITUITARY-TESTICULAR SYSTEM WITH AGE

In order to provide a comprehensive account of pituitary-testicular function in man, 466 subjects, ranging in age from 2 to 101 years, were studied to examine blood levels of the pituitary gonadotrophins (LH and FSH), the sex steroids testosterone and oestradiol, the binding capacity of the sex hormone binding globulin (SHBG), the free testosterone and oestradiol fractions, and the transfer constant for the peripheral conversion of testosterone to oestradiol. The results were compared with clinical indices of testicular size, sexual function and secondary sex hair distribution. Serum LH and FSH were low before puberty, increased in pubertal adolescents to levels somewhat above those of adults and subsequently increased progressively over the age of 40 years. Testosterone levels fell slowly after the age of 40, while there was a slight rise in plasma oestradiol with increasing age. FSH and testosterone showed small seasonal variations in young adult men, the lowest values being seen in winter. SHBG binding capacity was high in two prepubertal boys, fell in adult men, but increased in old age. Free testosterone and oestradiol levels fell in old age. The metabolic clearance rates (MCR) of testosterone and oestradiol also fell in old age, while the conversion of testosterone to oestradiol was increased. Many correlations were observed between various hormonal and clinical measurements. The evidence is consistent with a primary decrease in testicular function over the age of 40 years.     

Exercising attention within the classroom

Aim To investigate whether increased physical exercise during the school day influenced subsequent cognitive performance in the classroom. Method A randomized, crossover‐design trial (two weeks in duration) was conducted in six mainstream primary schools (1224 children aged 8–11y). No data on sex was available. Children received a teacher‐directed, classroom‐based programme of physical exercise, delivered approximately 30 minutes after lunch for 15 minutes during one week and no exercise programme during the other (order counterbalanced across participants). At the end of each school day, they completed one of five psychometric tests (paced serial addition, size ordering, listening span, digit‐span backwards, and digit‐symbol encoding), so that each test was delivered once after exercise and once after no exercise. Results General linear modelling analysis demonstrated a significant interaction between intervention and counterbalance group (p<0.001), showing that exercise benefitted cognitive performance. Post‐hoc analysis revealed that benefits occurred in participants who received the exercise intervention in the second but not the first week of the experiment and were also moderated by type of test and age group. Interpretation Physical exercise benefits cognitive performance within the classroom. The degree of benefit depends on the context of testing and participants’ characteristics. This has implications for the role that is attributed to physical exercise within the school curriculum.     

Level of purposeful hand function as a marker of clinical severity in Rett syndrome

Aim We investigated relationships between hand function and genotype and aspects of phenotype in Rett syndrome. Method Video assessment in naturalistic settings was supplemented by parent‐reported data in a cross‐sectional study of 144 females with a mean age of 14 years 10 months (SD 7y 10mo; range 2y–31y 10mo), 110 of whom had a mutation of the methyl CpG binding protein 2 (MECP2) gene. Ordinal logistic regression was used to assess relationships between hand function and MECP2 mutation, age, a modified Kerr score, Functional Independence Measure for Children (WeeFIM), ambulation level, and frequency of hand stereotypies. Results Approximately two‐thirds of participants demonstrated purposeful hand function, ranging from simple grasping skills to picking up and manipulating small objects. In participants with a confirmed MECP2 mutation, those with the p.R168X mutation had the poorest hand function on multivariate analysis with C‐terminal deletion as the baseline (odds ratio [OR] 0.19; 95% confidence interval [CI] 0.04–0.95), whereas those with the p.R133C or p.R294X mutation had better hand function. Participants aged 19 years or older had lower hand function than those aged less than 8 years (OR 0.36; 95% CI 0.14–0.92). Factors that were associated with better hand function were lower Kerr scores for a 1‐point increase in score (OR 0.77; 95% CI 0.69–0.86), higher WeeFIM scores for a 1‐point increase in score (OR 1.08; 95% CI 1.04–1.12), and greater ambulation than those completely dependent on carers for mobility (OR 22.64; 95% CI 7.02–73.08). The results for participants with a confirmed pathogenic mutation were similar to results obtained when participants without a mutation were also included. Interpretation Our novel assessment of hand function in Rett syndrome correlated well with known profiles of common MECP2 mutations and overall clinical severity. This promising assessment could measure clinical responses to therapy.