Human immunodeficiency virus infection in disadvantaged adolescents. Findings from the US Job Corps

OBJECTIVE--To describe the human immunodeficiency virus (HIV) epidemic among socially and educationally disadvantaged young persons in the United States. DESIGN.-We analyzed demographic and geographic findings from the screening of Job Corps students for antibody to HIV. SETTING--The Job Corps is a federal training program for disadvantaged, out-of-school youth. POPULATION SCREENED--Residential students aged 16 to 21 years who entered the Job Corps from October 1987 through February 1990. MAIN OUTCOME MEASURE--Rates of observed HIV infection in entering students, stratified by demographic and geographic features. RESULTS--Of 137,209 Job Corps students screened, 488 were HIV seropositive (3.6 per 1000), a seroprevalence rate higher than that among military applicants of the same age. Overall seroprevalence was slightly higher in male (3.7 per 1000) than in female (3.2 per 1000) Job Corps students, but among those students aged 16 and 17 years, seroprevalence was higher among females (2.3 per 1000) than among males (1.5 per 1000) (P less than .05). For students aged 16 to 21 years, seroprevalence increased with year of age: 1.8 per 1000 per year for males and 0.7 per 1000 per year for females. Among those aged 21 years, HIV prevalence was 8.9 per 1000. For black and Hispanic students from large Northeastern cities, seroprevalence increased by 4.3 per 1000 per year of age and reached 24.8 per 1000 (one of 40) in students aged 21 years. However, among students from rural areas and small towns, HIV seroprevalence was disproportionately high in the Southeast. Compared with recently described US patients with the acquired immunodeficiency syndrome, HIV-infected students who entered the Job Corps were much more likely to be female. CONCLUSIONS--These findings show that disadvantaged, out-of-school adolescents are at high risk for HIV infection. The screening results identified surprisingly high seroprevalence in the southeastern United States and demonstrated a marked shift in the HIV epidemic to young women. Controlling the HIV epidemic among teenagers must include interventions that will reach adolescents early and outside of the formal educational system.     

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.     

Chronic orchialgia: Consider gabapentin or nortriptyline before considering surgery

OBJECTIVE: To establish if there is a role for gabapentin or nortriptyline in the treatment of chronic orchialgia. METHODS: Twenty-six consecutive patients with chronic orchialgia were seen in the chronic pain clinic by a multidisciplinary team. A pain questionnaire was completed prior to commencing either gabapentin or nortriptyline. They were reviewed at 3 months and a repeat questionnaire completed. A 50% improvement in pain was considered successful. RESULTS: Complete data was available for 19 patients. Overall, 61.5% of patients commenced on gabapentin and 66.6% of patients commenced on nortriptyline had a greater than 50% improvement in pain. Patients with post-vasectomy testicular pain were considered as a subgroup. None of these patients had a greater than 50% improvement in pain. However, 80% of patients in the subgroup with idiopathic chronic orchialgia had a greater than 50% improvement in pain. CONCLUSION: Although this is a small study, it appears that gabapentin and nortriptyline are effective in the treatment of idiopathic chronic orchialgia but not post-vasectomy pain.     

Interaction of permanently charged chlorpromazine and dopamine analogs with the striatal D-1 dopaminergic receptor

Although a structural feature common to all dopaminergic agonists and antagonists is a side-chain basic amino group, it is unclear whether this moiety binds to the D-1 dopamine (DA) receptor in the charged or uncharged form. To obtain information on this point, we synthesized permanently charged dimethylsulfonium and quaternary ammonium analogs of chlorpromazine and DA and determined whether these compounds can bind to the D-1 receptor by measuring their abilities to inhibit the binding of SCH 23390, a D-1 receptor antagonist. Chlorpromazine and the dimethylsulfonium and trimethylammonium analogs of chlorpromazine were found to inhibit the binding of [3H]SCH 22390, which was maximally inhibited to the same extent by all three compounds. In addition, inhibition curves for the compounds fit a one-site binding model, indicating binding to a single class of sites. However, while the permanently charged chlorpromazine analogs were able to inhibit [3H]SCH-23390 binding, they were considerably less potent than chlorpromazine. DA and dimethyl DA were also able to inhibit [3H]SCH 23390 binding. However, the permanently charged dimethylsulfonium and trimethylammonium analogs of DA were ineffective in inhibiting [3H]SCH 23390 binding. In addition, the permanently uncharged methylsulfide analog did not inhibit binding. These studies show that permanently charged analogs of chlorpromazine can bind to the striatal D-1 receptor, which is consistent with an anionic recognition site on the D-1 receptor that interacts with antagonists in the cationic form. In addition, it appears that a nitrogen atom is not required for binding to the D-1 receptor, since the sulfonium analog of chlorpromazine bound to the receptor to the same extent as chlorpromazine. However, since the permanently charged or uncharged analogs of DA did not bind to the D-1 receptor, it is still unclear as to whether the charged form of a dopaminergic agonist can bind. The lower potency or ineffectiveness of the permanently charged analogs compared to the parent amines (chlorpromazine, DA, dimethyl DA) in binding to the D-1 receptor may reflect the inability of the permanently charged analogs to undergo hydrogen binding with the anionic site of the receptor.     

Congenital rubella in babies of south Asian women in England and Wales: an excess and its causes

The incidence of congenital rubella was found to be 2.3 times higher in Asian than non-Asian births in England and Wales. This was attributed in part to higher susceptibility to rubella in Asian than non-Asian women, as shown by antenatal serological data from public health laboratories in Leeds, Luton, and Manchester. Examination of the ethnic origin of pregnant women requesting laboratory testing after contact with rubella or rash and of women with laboratory confirmed rubella in pregnancy also suggested that the disease was being underdiagnosed in pregnant Asian women. Failure to prevent congenital rubella by termination of infected pregnancies may therefore contribute to the increased incidence of the syndrome in Asians. Health education programmes about the dangers of rubella in pregnancy and of the need for vaccination can readily be promoted in the Asian community through existing ethnic organisations. Protection of other ethnic minorities likely to be at similar increased risk may require a vaccination programme aimed at national elimination of rubella.     

An analysis of the paradoxical effect of morphine on runway speed and food consumption

A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference. Offprint requests to: W.A.CorrigallThe views expressed in this publication are those of the authors and do not necessarily reflect those of the Addiction Research Foundation     

Molecular targeted therapy for advanced hepatocellular carcinoma

Systemic anticancer therapy for hepatocellular carcinoma (HCC) is limited by intrinsic drug resistance and accompanying liver dysfunction. However, recent advances in molecular targeted therapy (MTT) have shed light on the treatment of advanced HCC. A recent randomized, placebo-controlled trial demonstrated that sorafenib, a multi-target tyrosine kinase inhibitor, prolonged overall survival and time-to-progression in patients with advanced HCC. This breakthrough highlights the potential of MTT targeting hepatocarcinogenic pathways, such as the Raf/MAPK/ERK pathway, angiogenic pathways and the EGFR signaling pathway. This review discusses the current status and the potential of developing novel MTTs for advanced HCC.     

Contribution of Gender to Pathophysiology and Clinical Presentation of IBS: Should Management Be Different in Women?

The irritable bowel syndrome (IBS) is found more commonly in women than men. It is more prevalent in patients with chronic fatigue syndrome, fibromyalgia, and chronic pelvic pain, all syndromes characterized by pain and found predominantly in women. This article reviews evidence for a role of biological sex factors and gender on the pathways mediating visceral pain. The effect of gonadal hormones on gastrointestinal motility and the sensory afferent pathway and central processing of visceral stimuli and the contribution of gender role to the clinical presentation are discussed. Although differences in responses to treatment modalities between genders exist, the approach to IBS patients in both genders is quite similar. Nevertheless, a special attention to gender role and stress-related factors should be addressed. New developments in research, outlined in the paper, might bring more gender-specific treatments in the future.