Oral Rehabilitation of a Patient With Amelogenesis Imperfecta

A patient with Type I hypoplastic patterned amelogenesis imperfecta, subtype D, presented for prosthodontic evaluation. This article describes the developmental and pathophysiological background of this disease. A clinical report describing the diagnosis, treatment planning, and dental rehabilitation of the patient is reviewed.     

Optimizing Suicide Gene Therapy for Head and Neck Cancer

An effective “suicide gene” therapy strategy in experimental studies has been the use of the herpes simplex virus thymidine kinase gene(HSV-tk) to sensitize tumors to the cytotoxic effects of ganciclovir administration. Previous studies using this model have focused on utilizing maximal viral titers and high levels of ganciclovir that are not compatible with human dosing. Because of the high ganciclovir doses and the maximal viral titers, this strategy has limited application to actual clinical scenarios. In the following studies the authors investigate tumor regression in an oral squamous cell carcinoma animal model as a function of variable adenoviral titers and more physiologic ganciclovir dosing. Using adenoviral titers ranging from 1 × 10⁸ to 2 × 10⁹ plaque forming units(pfu) to treat oral tumors, they found no statistical difference in tumor regression among the different viral doses, despite differences in mitotic activity. Each treatment group, however, demonstrated a significant effect on tumor regression when compared with controls. Furthermore, the authors were able to reduce the level of ganciclovir administration to 10 mg/kg twice daily from established levels of 100 to 150 mg/kg twice daily while maintaining significant tumor responses to the HSV-tk therapy. Mean survival of animals treated with this lower ganciclovir dose was significantly higher than in controls and was equal to established means based on previous studies using higher ganciclovir doses. The optimization of this suicide gene therapy strategy is imperative in order to minimize theoretical and known viral and ganciclovir toxicities while establishing a foundation upon which to design appropriate and effective clinical trials.     

Mental object rotation in Parkinson's disease.

Deficits in visual-spatial ability can be associated with Parkinson's disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated.     

Decreased platelet vesicular monoamine transporter density in habitual smokers.

The brain vesicular monoamine transporter (VMAT2) is part of the re-uptake mechanism which regulates monoaminergic neurotransmission. We demonstrated previously a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. Nicotine induced increase of dopamine and serotonin neurotransmission in limbic structures may alter the expression of VMAT2 in brains of smokers. In this study we measured the VMAT2 pharmacodynamic characteristics using high-affinity [3H]dihydrotetrabenazine (TBZOH) binding to platelets of smokers (n=15) compared to sex and age matched healthy nonsmokers controls (n=14). A significant decrease (17%, P=0.02) in VMAT2 density (Bmax) was observed in platelets of smokers compared to nonsmokers. There was no significant difference in the affinity of [3H]TBZOH to its platelet binding site and the VMAT2 density did not correlate with the heaviness of smoking. The decreased density of the VMAT2 in the platelets of smokers may reflect nicotine induced desensitization of VMAT2, a phenomenon that may be relevant to the addictive properties of nicotine.     

Longitudinal changes in IQ among fragile X males: clinical evidence of more than one mutation?

Longitudinal changes in IQ among mentally retarded (MR) fragile X [fra(x)] males have been reported previously. While age is associated with decline in IQ, not all males are so affected. This suggests that there may be more than one subtype of affected fra(X) male. Therefore, we examined the distribution of standardized difference scores (Zdiff) in IQ to determine if subjects were from an admixture of at least 2 populations. Cluster analysis of Zdiff scores was used to partition subjects into 2 groups. Goodness-of-fit tests indicated that scores were more likely to come from an admixture. Discriminant functions (DF) were calculated to determine predictive validity of Zdiff scores. To eliminate the effect of skewing, a power transform was applied to Zdiff scores and DFs recomputed. Zdiff and transformed scores provided similar results. The mean and variance for one group showed no differences in test-retest scores as would be expected from examining any population while the mean for the second group indicated significant decline in IQ nearly 4 standard errors below the first test score. These results suggest that there may be clinical evidence for 2 types of fra(X) mutation: One which causes MR but is static, and a second mutation which causes MR but is dynamic and contributes to an apparent longitudinal decline in cognitive function.     

Risk of recurrence of birth defects in Washington State

A population-based study was conducted using maternally-linked birth certificate records from Washington State for 1980–93 to evaluate the risk of birth defect occurrence among infants with pre-viously affected siblings, relative to infants whose siblings did not have birth defects. The risks of recurrence of similar and dissimilar defects were estimated, and the effects of change in paternity and/or city of residence were evaluated as proxies of genetic and environmental effects. At the first birth on record, 3322 women were identified in the linked certificates as giving birth to a child with a birth defect; 6620 women whose first birth did not result in an infant with a defect were randomly selected for comparison. Women with a malformed infant had an in-creased risk of having a malformed infant at the subsequent birth (Relative Risk = 1.9, [95% Confidence Interval (CI) = 1.5–2.4]), which did not vary by intervening changes in partner or residence. The risk of recurrence of the same general type of defect [RR = 11.7, 95% CI = 9.7–19.50] was much greater than that of occurrence of a dissimilar defect [RR = 1.5, 95% CI = 1.1–1.9]. This was consistent for all defect categories, and did not vary markedly by changes in partner or residence.