Increased plasma pyridoxal-5′-phosphate levels before and after pyridoxine loading in carriers of perinatal/infantile hypophosphatasia

Summary We measured plasma levels of pyridoxal-5-phosphate (PLP), a cofactor form of vitamin B6 and apparent natural substrate for alkaline phosphatase (ALP), in carriers and in non-carriers of the severe perinatal and infantile forms of hypophosphatasia, both before and after an oral load of pyridoxine (i.e. 1/3 mg/kg body weight). The assignment of carrier status was determined by serum ALP activity, level of serum inorganic phosphate, and if necessary urinary phosphoethanolamine excretion. Plasma PLP levels were significantly increased in the carriers both before and especially after B6 loading.     

Toward standardization of health information

NCVHS has made recommendations to the DHHS to standardize 42 core health data elements, a number of which relate to medical conditions and services. The committee has asked the DHHS Data Council to actively promote, both within the department and externally, standardization of data elements and definitions where substantial consensus already exists. For those elements that have been recognized as significant core data elements, but for which there is not consensus on approach or definition, the NCVHS is recommending that the Data Council support the formation of a public-private working group to conduct further study and evaluation. This group, or a separate group, could also be the focus for evaluating additions to the list of core data elements and for setting up methods for testing and promulgating the final products. The coming 12-18 months will be exceedingly important for health data standardization efforts in the US as the DHHS responds to both the NCVHS recommendations and the legislation recently enacted by Congress.     

An assessment of a urinary biomarker for total human environmental exposure to benzo[a]pyrene

Urinary banzo[a]pyrene (BaP) metabolite levels were compared to human environmental exposure to BaP through inhalation and dietary ingestion to assess the predictive validity of the exposure biomarker. These measurements were made for 14 adult volunteers over 14 consecutive days, once during summer/fall, again during winter periods. Based on personal air monitoring, median potential inhalation doses of 11.0 and 2.3 ng/day were estimated for the winter and summer/fall studies, respectively. A median potential ingested dose of 176 ng/day, estimated from duplicate plate sampling, exceeded inhalation by 6-and 122-fold for the winter and summer/fall studies, respectively. Total urinary BaP metabolites were measured using a published reverse metabolism (BaP) method of analysis. Median rates of urinary BaP metabolite elimination for the winter and summer/fall studies were 121 and 129 ng/day, respectively. The changes in inhaled and ingested potential doses were regressed on the change in urinary metabolite elimination from week 1 to week 2 to test the predictive validity of the biomarker measurement. The regression was statistically significant (r = 0.620, p = 0.015, n = 25) when body weight was included and two extreme values were removed. Consistent with the exposure measurements showing diet as the dominant route of exposure, most of the variation in urinary metabolite elimination was explained by the ingested dose. It is concluded that the measurement of urinary BaP by reverse metabolism is qualitative and of marginal predictive validity as an exposure biomarker due to the method's low recoveries and the large unexplained variance.     

Gender differences in HIV risk behaviors in an adult emergency department in New York City

Background The human immunodeficiency virus (HIV) epidemic in the US increasingly involved urban heterosexual adults, particularly women, belonging to ethnic minority groups. An understanding of gender-based differences in HIV risk behaviors within these groups would be of value in the ongoing struggle to limit HIV transmission in metropolitan centers. Methods This was a prospective study of demographic and historical characteristics and HIV risk behaviors. The study utilized a structured interview format, which was administered to all patients treated by participating emergency department physicians. Results On univariate analysis of data obtained from 1,460 patients who had neither a known HIV infection nor a chief complaint or final emergency department diagnosis associated with HIV risk behaviors, men were more likely to be older, homeless, to have ever injected drugs, used crack, engaged in same-gender sex, paid for sex, been incarcerated, or had syphilis or gonorrhea. Women were more likely to report prior chlamydia infection or to report that their sole sex partners had other partners within the past year. On multivariate analysis, variables independently associated with male gender included homelessness, injection drug use, crack use, any prior sexually transmitted disease (in subjects 35 years of age or older), and sex with prostitutes. In a separate analysis of patients admitting to drug use, the male predominance of other risk behaviors was not observed; the only significant differences between genders were a higher rate of prostitution among women and a higher rate of sexual contact with a prostitute among men. Conclusions In patients visiting an inner-city emergency department in the Bronx, HIV risk behaviors are generally more common in men, but rates of risk behaviors among male and female drug users are comparable. This work was supported in part by a collaborative agreement with the Centers for Disease Control and Prevention (U64/CCU200714). Drs. Shuter, Alpert, and DeShaw were supported in part by a training grant (5-T32-AI070183) from the National Institute of Allergy and Infectious Diseases. This study was presented in part at the 32nd Annual Meeting of the Infectious Diseases Society of America, October 1994, Orlando, Florida.     

Agenesis of the penis: patterns of associated malformations

Agenesis of the penis is a rare malformation that occurs in otherwise normal males or together with other anomalies. In this article, we document unusual patterns of malformations in four such infants and analyze the nature and incidence of defects in 57 cases by clinical evaluation and numerical classification techniques. Although patients with this condition previously have been divided into groups based on the position of the urethral meatus in relation to the anus (presphincteric, postsphincteric, urethral atresia), our analyses suggest that most cases can be classified into either a severe form (16%) with renal aplasia or dysplasia and other caudal anomalies or a second group (72%) with low mortality and fewer additional malformations. The remaining cases in our group represented unique patterns stemming from a variety of causes, including etretinate embryopathy and the human homologue of the disorganization mutation. Agenesis of the penis occurs as a consequence of single gene disorders, teratogenic effects, or malformation sequences and associations and in unrecognized patterns of anomalies. It thus should be considered a developmental field defect. Its concurrence with scrotal hypoplasia, absent raphe, and anal anomalies implies a major disturbance of the caudal mesoderm. In such cases, severe renal defects are usually seen, and the prognosis is poor. When the patient has a patent urethra and normal scrotum, raphe, and testes, however, penile agenesis may be a localized malformation of the genital tubercle potentially related to penoscrotal transposition, a phylogenetic anomaly that is the normal genital arrangement in male marsupials, rabbits, and certain other mammals. Infants with isolated penile agenesis have generally done well. In the past, many were not treated; however, current recommendations are to use appropriate surgical and endocrine techniques to reassign female gender and enhance sexual and psychosocial functioning, though this approach is the subject of controversy.     

Ventricular function

Multiple modalities contribute to the evaluation of ventricular function. The role of cineangiography, echocardiography, MR imaging, ultrafast CT, and nuclear medicine continue to evolve and improve our understanding of the physiology and pathophysiology of ventricular function. This article discusses the use and limitation of each modality.     

Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS

In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency < or = 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression.     

Early castration reduces prostatic carcinogenesis in transgenic mice

Objectives. To test the hypothesis that transgenic mouse models of prostate cancer could be useful for testing chemoprevention strategies by evaluating the effects of early castration on prostate carcinogenesis in TRAMP mice. Human prostate cancer, unlike other cancers, requires androgens for oncogenesis yet acquires partial androgen independence in the castrated milieu. This paradigm is the basis for an ongoing clinical trial using selective androgen deprivation for prostate cancer chemoprevention. However, preclinical correlates for hormonal prevention or other chemoprevention strategies of prostate cancer have not previously been demonstrated in autochthonous models of prostate carcinogenesis.Methods. Magnetic resonance imaging was used to longitudinally measure prostate growth in castrated and noncastrated TRAMP mice, and mice were prospectively examined for the onset of advanced, palpable prostate cancer. Modulation of androgen-responsive oncogene expression, as well as oncogene expression in refractory cancers, was evaluated by Western blot.Results. Early castration significantly reduced prostate tumor growth as measured by magnetic resonance imaging and improved cancer-free survival. Prevention of prostate cancer development in these mice was associated with durable suppression of androgen-responsive oncogene expression (T-antigen expression not detectable by Western blot); prostate cancers refractory to the hormonal prevention strategy demonstrated androgen-independent oncogene expression.Conclusions. These findings suggest that carcinogenesis related to androgen-responsive oncogene expression can be prevented in some cases by hormonal manipulation and that transgenic TRAMP mice are useful for the preclinical evaluation of hormonal and possibly other strategies of prostate cancer chemoprevention.