Recent Publications by CFE Educators

Mutations in reeler, the gene coding for the Reelin protein, result in pronounced motor deficits associated with positioning errors (i.e. ectopic locations) in the cerebral and cerebellar cortices. In this study we provide the first evidence that the reeler mutant also has profound sensory defects. We focused on the dorsal horn of the spinal cord, which receives inputs from small diameter primary afferents and processes information about noxious, painful stimulation. We used immunocytochemistry to map the distribution of Reelin and Disabled-1 (the protein product of the reeler gene, and the intracellular adaptor protein, Dab1, involved in its signaling pathway) in adjacent regions of the developing dorsal horn, from early to late embryonic development. As high levels of Dab1 accumulate in cells that sustain positioning errors in reeler mutants, our findings of increased Dab1 immunoreactivity in reeler laminae I-III, lamina V and the lateral spinal nucleus suggest that there are incorrectly located neurons in the reeler dorsal horn. Subsequently, we identified an aberrant neuronal compaction in reeler lamina I and a reduction of neurons in the lateral spinal nucleus throughout the spinal cord. Additionally, we detected neurokinin-1 receptors expressed by Dab1-labeled neurons in reeler laminae I-III and the lateral spinal nucleus. Consistent with these anatomical abnormalities having functional consequences, we found a significant reduction in mechanical sensitivity and a pronounced thermal hyperalgesia (increased pain sensitivity) in reeler compared with control mice. As the nociceptors in control and reeler dorsal root ganglia are similar, our results indicate that Reelin signaling is an essential contributor to the normal development of central circuits that underlie nociceptive processing and pain.

TRPA1 is an excitatory ion channel targeted by pungent irritants from mustard and garlic. TRPA1 has been proposed to function in diverse sensory processes, including thermal (cold) nociception, hearing, and inflammatory pain. Using TRPA1-deficient mice, we now show that this channel is the sole target through which mustard oil and garlic activate primary afferent nociceptors to produce inflammatory pain. TRPA1 is also targeted by environmental irritants, such as acrolein, that account for toxic and inflammatory actions of tear gas, vehicle exhaust, and metabolic byproducts of chemotherapeutic agents. TRPA1-deficient mice display normal cold sensitivity and unimpaired auditory function, suggesting that this channel is not required for the initial detection of noxious cold or sound. However, TRPA1-deficient mice exhibit pronounced deficits in bradykinin-evoked nociceptor excitation and pain hypersensitivity. Thus, TRPA1 is an important component of the transduction machinery through which environmental irritants and endogenous proalgesic agents depolarize nociceptors to elicit inflammatory pain.

OBJECTIVE

Antiretroviral-treated individuals with drug-resistant HIV experience slower CD4 cell count declines than untreated individuals, independent of degree of viremia. As immune activation independently predicts disease progression, we hypothesized that patients with drug-resistant viremia would have less immune activation than patients with wild-type viremia, independent of plasma HIV RNA levels and that these differences would not be explained by a direct drug effect of protease inhibitors.

METHODS

Percentages of activated (CD38/HLA-DR) T cells were compared between untreated participants with wild-type viremia and antiretroviral-treated participants with drug-resistant viremia, after adjusting for plasma HIV RNA levels among other factors associated with T cell activation. Changes in T cell activation were also assessed in subjects discontinuing protease inhibitors while continuing other antiretroviral medications.

RESULTS

Twenty-one untreated participants with wild-type viremia and 70 antiretroviral-treated participants with drug-resistant viremia were evaluated. Relative to untreated participants, those with drug-resistant viremia had 29% fewer activated CD4 (P = 0.051) and CD8 (P = 0.012) T cells after adjustment for plasma HIV RNA levels among other factors. There was no evidence for an early change in T cell activation among 13 subjects with drug-resistant viremia interrupting protease inhibitors while continuing other antiretroviral medications, but a significant increase in T cell activation with complete or partial emergence of wild-type sequences in protease.

CONCLUSIONS

Antiretroviral-treated patients with drug-resistant viremia have less T cell activation than untreated patients, independent of plasma HIV RNA level. Decreased ability of drug-resistant variants to cause T cell activation likely contributes to slower CD4 cell count declines among patients with drug-resistant viremia.

Atopic dermatitis is an extremely common childhood skin disease that can have far-reaching impact on patients and families. Pediatric patients, particularly infants, pose special concerns for parents and providers, and equal emphasis must be placed on both nonpharmacologic and prescription interventions. Concerns for adverse effects of prescription therapies and a universal parental fear of an undetected allergy are hallmarks of pediatric atopic dermatitis care. The purpose of the present study is to highlight important educational and therapeutic strategies designed to optimally care for this patient population.

Andersen-Tawil syndrome (ATS) is an autosomal dominant multisystem disorder characterized by developmental, cardiac, and neuromuscular abnormalities. Approximately 70% of patients have mutations in KCNJ2, resulting in dysfunction of the inward-rectifying potassium channel Kir2.1. Variable expression complicates the diagnosis of ATS, which in many cases, is not made until years after the first recognized symptom. To better define the distinctive clinical features of ATS and facilitate earlier diagnosis, we conducted a prospective, standardized evaluation of 10 subjects with confirmed KCNJ2 mutations. Detailed anthropometric, neurological, and cardiac evaluations were performed. Using this approach, we identified novel skeletal and dental findings and proposed additional diagnostic criteria for ATS dysmorphology.

AIMS

Lymphadenectomy in the management of papillary thyroid cancer (PTC) has evolved. The aim of this study was to examine the changing role of neck dissection as reflected in the practice of a large thyroid unit over four decades.

METHODS

A retrospective cohort study of patients that underwent primary thyroid surgery for papillary cancer in a single unit in the period 1958-2002. Nine 5-year periods were considered and the data relevant to the treatment of the regional lymph nodes reviewed.

RESULTS

Nine hundred patients with PTC underwent surgery between 1958 and 2002 of whom 32.7% underwent lymph node dissection (LND). The use of lymphadenectomy increased from 21.4% in 1958-1962 to 48.1% in 1998-2002 of which 84% underwent a selective lymph node dissection (SLND)-a dissection where the LND is determined by the extent of the disease encountered. The mean number of nodes removed during SLND was 12.6 (range 1-56) of which a mean of 3.1 (24.8%) (0-19) were involved by the disease. Cervical levels 6 and level 4 were those most frequently dissected. There was no statistically significant difference in the complication rates in patients undergoing neck dissection and those not.

CONCLUSION

The four decade experience reflects a move away from modified radical neck dissection and cherry picking towards SLND. Growing evidence suggests that lymphadenopathy in adult PTC is an adverse prognostic factor. SLND, a lymphadenectomy tailored to the extent of the disease process, is the coherent treatment for PTC since it serves the dual purpose of staging as well as control of local disease. This can be achieved with little morbidity when performed in a specialist centre.

Despite the evidence that attention-deficit/hyperactivity disorder (ADHD) is not just a diagnosis of whites, it often goes undiagnosed and is underresearched in the African-American population. There are higher rates of delinquency, incarceration, teen pregnancy and sexually transmitted diseases associated with inadequate or delayed treatment of ADHD. Afrcan Americans generally respond well to treatments, but access to evaluation, medication and psychotherapy is limited or absent for many, The purpose of this research is to compare descriptive characteristics of African-American children with ADHD to age-matched Caucasian children with the same diagnosis. Age at diagnosis, treatment offered, perception of outcome, adherence, comorbid symptoms and frequency of follow-up were collected retrospectively from charts of children treated in the sections of child and adolescent psychiatry and pediatric neurology.