Atypical phenylketonuria with normal phenylalanine hydroxylase and dihydropteridine reductase activity in vitro.

A child with phenylketonuria had normal phenylalanine hydroxylase activity in vitro. In addition, all known components of the phenylalanine hydroxylating system were within the normal range. Despite early treatment with a phenylalanine-restricted diet, the patient developed severe neurological symptoms. Although the primary molecular defect in this child is not known, there are indications that the defect lead to disturbances in phenylalanine metabolism and the biosynthesis of L-dopa and L-5-hydroxytryptophan. The administration of these two precursors of neurotransmitters brought a notable improvement in the patient's neurological symptoms.     

Moderate chronic pain, weight and dietary intake in African-American adult patients with sickle cell disease

In this exploratory study, we evaluated weight status and dietary intake patterns during painful episodes in adult patients with SCD. Specifically, we explored the relation between pain severity and body mass index (BMI), and we tested the hypothesis that dietary intake would be reduced and dietary content altered during periods of increased pain. We conducted an analysis of survey data from 62 patients involved in a longitudinal evaluation of the relationship of medical and psychosocial factors to pain. Nearly half of patients with SCD were overweight, and 20% were obese. BMI was positively related to interference associated with pain. Although BMI was not statistically associated with reported pain severity, >40% of patients reported that they perceived their pain to be affected by their weight. Less than 20% of patients reported that they perceived that their weight affected their pain. Regarding dietary patterns, the majority of patients reported eating less during episodes of pain and significantly decreasing their intake of fats and proteins. We conclude that there is a need to better understand the relation among weight, dietary patterns and pain in patients with SCD in order to provide patients with accurate education and effective treatment recommendations for managing their disease and reducing current and future risks of lifestyle and disease-related morbidities.     

Cervical cancer screening beliefs among young Hispanic women

OBJECTIVES: This study examined beliefs, attitudes, and personal characteristics that correlated with self-reported cervical cancer screening history among Hispanic women aged 18 to 25 years old in El Paso, TX, a large metropolitan area on the U.S.-Mexico border. METHODS: Data were collected through a cross-sectional, face-to-face survey. The study questionnaire was based primarily on the Health Belief Model, and included scales that measured perceived susceptibility and seriousness of cervical cancer, and perceived benefits and barriers to Pap test screening. The study questionnaire also included measures of acculturation, Pap test history, pregnancy and sexual history, use of birth control, type of medical insurance, and educational attainment. RESULTS: Sixty-nine percent reported ever having had a Pap test and 56% reported having had a test in the past year. Eighty percent reported that they were sexually active, and of these, 63% reported using birth control. Respondents understood the seriousness of cervical cancer, their susceptibility to cervical cancer, and the benefits of Pap testing; however, only 61% agreed that most young women whom they know have Pap tests. Greater acculturation and the belief that most young unmarried women have Pap tests were positively associated with ever having screening. The perception that the test would be painful and not knowing where to go for the test were negatively associated with ever having a Pap test. CONCLUSIONS: This study found suboptimal rates of screening for cervical cancer in a sample of young Hispanic women residing along the U.S.-Mexico border. Although women may understand the seriousness of cervical cancer and the benefits of screening, perceptions about Pap tests may pose barriers to undergoing screening. Efforts to increase screening also may need to focus specifically on women who are least acculturated, as they also were least likely to have had prior Pap tests.     

Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors

Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC(50) in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn(2+)-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic omega-amino acid linkers. This strategy has led to a novel class of Zn(2+)-chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIP1) expression, which are hallmark features associated with intracellular HDAC inhibition.     

Advanced presentation of melanoma in African Americans

BACKGROUND: Melanoma in African Americans is rare, and the diagnosis is often delayed, leading to advanced presentation and poor prognosis. OBJECTIVE: The purpose of this retrospective study is to determine whether African American patients diagnosed with melanoma at the Washington Hospital Center were initially seen with more advanced disease than white patients. METHODS: A retrospective chart review was performed on 36 African American patients who were diagnosed and/or treated for melanoma at the Washington Hospital Center between 1981 and 2000. Data obtained included patient age at presentation, sex, Breslow's depth and histologic subtype, stage at presentation, and tumor location. These data were compared with information obtained from white patients with melanoma during this period. RESULTS: A total of 649 African American and white patients were treated for melanoma at the Washington Hospital Center between 1981 and 2000. Of these, 36 (6.1%) patients were African American. African American patients were more likely to initially be seen with stage III/IV disease (32.1%) compared with (12.7%) the white patients initially seen with these disease stages. Of the white patients 60.4% were initially seen with melanoma in situ/stage I disease compared with 39.3% of the African American patients. The 5-year survival rate was 58.8% in African Americans compared with 84.8% in whites. CONCLUSIONS: In our series, African Americans are more likely than whites to be initially seen with advanced disease and have a subsequent worse prognosis. Physician training and patient education campaigns are crucial to improving the poor prognosis associated with melanoma in the African American community.     

Inhibin-A and superimposed preeclampsia in women with chronic hypertension

OBJECTIVE: To determine if maternal serum inhibin-A can be used as a marker for subsequent development of superimposed preeclampsia in women with chronic hypertension. METHODS: Serum for measurement of inhibin-A was obtained at monthly intervals in women with chronic hypertension requiring antihypertensive medications. Superimposed preeclampsia, the primary outcome of interest, was diagnosed when hypertensive women developed proteinuria (at least 300 mg per 24-hour urine specimen). Serum inhibin-A was considered abnormally elevated when the value exceeded the mean plus two standard deviations of the log for chronically hypertensive women who did not develop preeclampsia. RESULTS: A total of 61 women were enrolled in this study, and 21 (34%) developed superimposed preeclampsia. Inhibin-A levels increased with advancing gestational age. Ten women had abnormally increased inhibin-A levels; eight (80%) developed superimposed preeclampsia, compared with 13 of 51 (26%) women with normal inhibin-A levels (P <.001). Sensitivity and specificity were 38% and 95%, respectively, whereas the positive and negative predictive values were 80% and 75%, respectively. CONCLUSION: Although inhibin-A was abnormally increased an average of 3 weeks before the clinical onset of superimposed preeclampsia, the sensitivity of the test as a screen was too limited to be clinically useful.     

Blastomycosis of the vocal folds with life-threatening upper airway obstruction: a case report

Blastomycosis is a chronic fungal disease that primarily affects the lower respiratory tract. The acute inflammatory phase of the primary pulmonary infection is characterized by a lymphohematogenous spread to extrapulmonary sites, especially the skin. The presence of disseminated infection with Blastomyces dermatitidis in the larynx is unusual. In areas of the United States where this fungus is endemic, failure to consider laryngeal involvement might lead to inappropriate therapy and thus worsening inflammation and airway compromise.