A prospective evaluation of the relationships between smoking dosage and body mass index in an adolescent,biracial cohort

Although there is clearly an inverse relationship between smoking and body weight, recent studies suggest that weight attenuation via smoking is slow and may take decades to accrue. This investigation prospectively evaluated the relationships between smoking dosage (or lack thereof) and relative weight change in 1697 adolescents followed over 4 years. A 4 (smoking groups: 0, 1, 2, or 3 or more years of smoking exposure)x2 (ethnicity: Caucasian or African American)x2 (gender: male or female) analysis of variance (ANOVA) was performed to assess weight gain attenuation associated with increasing exposure to smoking. The overall results revealed a significant three-way interaction between smoking dosage, gender, and ethnicity. Specifically, smoking initiation was associated with an increase in body mass index (BMI) for 2 years after initiation. For those youth smoking 3 or more years, body weights were almost identical compared to never-smokers. No significant reductions in body weight were observed in any gender or ethnic group for up to 3 years after smoking initiation. It is concluded that smoking initiation is not associated with adolescent body weight change for at least a 3-year period.     

Opioid detoxification with buprenorphine,clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.     

Comparison of recombinant derivatives of chimeric TNT-3 antibody for the radioimaging of solid tumors

Although intact monoclonal antibodies (MAbs) are well suited as therapeutic reagents, their relatively slow clearance rates render them less useful for imaging applications. Over the last several years, our laboratory has developed a unique targeting approach to solid tumors that utilizes MAbs directed against DNA and its components to bind to degenerating cells and necrotic regions of tumors in a specific manner. Because these MAbs have considerable potential for the early diagnosis of cancer and for the monitoring of cytoreductive therapies, the availability of an effective imaging agent is highly desirable. To accomplish this goal, a series of genetically engineered derivatives of MAb chTNT-3 including the single-chain Fv, diabody, triabody, Fab, and F(ab')(2) were generated and expressed in NS0 myeloma cells using the Glutamine Synthetase Amplification System. Initial in vitro studies demonstrated that each of the antibody derivatives maintained its antigen binding in a stable manner. In vivo analyses after radiolabeling were then performed to evaluate their pharmacokinetic, biodistribution, and tumor-imaging properties in solid tumor-bearing mice. The results of these studies showed that compared with intact parental chTNT-3, which has a half-life of 134.2 h, the smaller derivatives were eliminated more rapidly (4.9-8.1 h). Importantly, the smaller derivatives were found to have significantly higher tumor-to-organ ratios, but lower overall uptake levels compared with parental (125)I-chTNT-3 in two different tumor models. A comparison of the five derivatives showed that the F(ab')(2) reagent consistently gave the best results in imaging and biodistribution studies. Based upon these results, further studies are warranted to demonstrate the potential of this reagent for the diagnosis and monitoring of solid tumors using noninvasive imaging techniques such as immunoscintigraphy and positron emission tomography (PET).     

TNM: evolution and relation to other prognostic factors

The TNM Classification describes the anatomic extent of cancer. TNM's ability to separately classify the individual tumor (T), node (N), and metastasis (M) elements and then group them into stages differs from other cancer staging classifications (e.g., Dukes), which are only concerned with summarized groups. The objectives of the TNM Classification are to aid the clinician in the planning of treatment, give some indication of prognosis, assist in the evaluation of the results of treatment, and facilitate the exchange of information. During the past 50 years, the TNM system has evolved under the influence of advances in diagnosis and treatment. Radiographic imaging (e.g., endoscopic ultrasound for the depth of invasion of esophageal and rectal tumors) has improved the accuracy of the clinical T, N, and M classifications. Advances in treatment have necessitated more detail in some T4 categories. Developments in multimodality therapy have increased the importance of the "y" symbol and the R (residual tumor) classification. New surgical techniques have resulted in the elaboration of the sentinel node (sn) symbol. The use of immunohistochemistry has resulted in the classification of isolated tumor cells and their distinction from micrometastasis. The most important challenge facing users of the TNM Classification is how it should interface with the large number of non-anatomic prognostic factors that are currently in use or under study. As non-anatomic prognostic factors become widely used, the TNM system provides an inviting foundation upon which to build a prognostic classification; however, this carries a risk that the system will be overwhelmed by a variety of prognostic data. An anatomic extent-of-disease classification is needed to aid practitioners in selecting the initial therapeutic approach, stratifying patients for therapeutic studies, evaluating non-anatomic prognostic factors at specific anatomic stages, comparing the weight of non-anatomic factors with extent of disease, and communicating the extent of disease data in a uniform manner. Methods are needed to express the overall prognosis without losing the vital anatomic content of TNM. These methods should be able to integrate multiple prognostic factors, including TNM, while permitting the TNM system to remain intact and distinct. This article discusses examples of such approaches.     

A randomized controlled trial of interleukin-1 receptor antagonist in a rabbit model of ascending infection in pregnancy

OBJECTIVE: To determine whether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amniotic fluid concentrations of tumor necrosis factor alpha (TNF-alpha) and prostaglandins or clinical or microbiological outcomes in a model of ascending bacterial infection in pregnancy. METHODS: Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation of the cervices with 10(6) - 10(7) cfu Escherichia coli. Animals were randomly assigned in a blinded manner to a 5-h intravenous infusion of human IL1-ra (10 mg/kg) or placebo beginning 1-2 h after inoculation. Blood was drawn from the does for assay of serum IL1-ra concentration before inoculation, at mid-infusion, after the infusion ended and at necropsy. At necropsy, temperature and cultures were taken, and aspirated amniotic fluid was pooled for assays of TNF-aalpha, prostaglandin E2 (PGE2) and ILI-ra. RESULTS: Serum IL1-ra concentrations rose to a mean of 2 microg/ml at mid-infusion and fell markedly after the infusion to concentrations barely detectable at necropsy. Between the two groups, there were no significant differences in the rates of fever or positive cultures or in amniotic fluid concentrations of PGE2 or TNF-alpha. One unique finding was the demonstration that administration of human IL1-ra to the does resulted in measurable concentrations of human IL1-ra in the amniotic fluid. CONCLUSIONS: Treatment with an intravenous infusion of human IL1-ra after cervical inoculation with E. coli did not affect clinical or microbiological outcomes or amniotic fluid concentrations of TNF-alpha or PGE2. This experiment providesthefirstdemonstration of passage of human IL1-ra from the maternal bloodstream to the amniotic fluid.     

Inhibition of murine sperm-oolemma binding by antibodies to an oocyte membrane (OM) antigen: implication in contraceptive vaccine development

PROBLEM: The present study was conducted to investigate the oocyte membrane protein(s) that is involved in sperm binding in the mouse, and whether or not it can be used for the development of a contraceptive vaccine. METHOD OF STUDY: The zona-free oocytes were treated with Triton X-100 and the extract was analyzed for homogeneity in the sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) after staining with silver nitrate. The appropriate band of 50+/-4 kD, designated as OM antigen, was excised from the gel and used for the immunization. The female rabbits were immunized with the excised band per se and the female mice were immunized with the OM antigen after conjugation to keyhole limpet hemocyanin (KLH). The affinity-purified antibodies were analyzed in the enzyme-linked immunosorbent assay (ELISA), immunoprecipitation procedure, western blot procedure, indirect immunofluorescence technique (IFT), and spermoolemma binding assay. Actively-immunized mice were analyzed for in vivo fertility. RESULTS: The Triton X-100 extract of zona-free oocytes predominantly showed a single protein band of 50+/-4 kD in the SDS-PAGE. Active immunization of female rabbits and of female mice with OM antigen raised high antibody titers (ELISA titer > 1:4096) that specifically recognized the OM antigen in the immunoprecipitation and Western blot procedures, and reacted with the oocyte in the IFT. These antibodies demonstrated a significant (P < 0.05) up to a complete block of sperm-oolemma binding in the in vitro binding assay. Binding of both the acrosome-intact and acrosome-reacted sperm was inhibited. Mice actively immunized with OM antigen also showed a significant reduction in vivo fertility as seen by the 9-day implants in uteri. Preliminary data indicate that the antibodies to OM antigen were tissue-specific and did not react with the specific band in any tissue extract in the western blot procedure. CONCLUSIONS: These results indicate that the OM antigen is involved in spermoolemma binding and constitute an attractive molecule that needs further investigation for examining its utility in the contraceptive vaccine development.     

'Round-table' ethical debate: is a suicide note an authoritative 'living will'?

Living wills are often considered by physicians who are faced with a dying patient. Although popular with the general public, they remain problems of authenticity and authority. It is difficult for the examining physician to know whether the patient understood the terms of the advance directive when they signed it, and whether they still consider it authoritative at the time that it is produced. Also, there is little consensus on what spectrum of instruments constitutes a binding advance directive in real life. Does a ''suicide note'' constitute an authentic and authoritative ''living will''? Our panel of authorities considers this problem in a round-table discussion.     

E-Nursing: electronic nursing resources on your desktop

E-Nursing represents an innovative approach to nursing education that has the potential to support professional practice throughout the institution. This paper details the benefits, design and promotion of an electronic nursing resource collection. How to divide responsibility, cost and expertise in such a project is also discussed. Preliminary usage statistics validate E-Nursing as a point-of-care education tool for nurses at Mount Sinai Hospital. A planned approach to implementation has been an effective means of introducing E-Nursing in an institution that previously relied on traditional hard-copy resources housed in the hospital's library.     

Efficacy and time-efficiency of a "sonographer-driven" contrast echocardiography protocol in a high-volume echocardiography laboratory

Background Contrast echocardiography (CE) has not gained widespread use despite numerous studies demonstrating its efficacy in the assessment of left ventricular (LV) function. Methods We sought to determine whether CE could be used in a high-volume echocardiography laboratory in a clinically effective and time efficient manner. We implemented a protocol with a feasibility phase and an established phase. Cost-benefit analyses were done on the basis of time use. Results During the feasibility and established phases, data on 119 and 672 patients, respectively, were obtained. After a “sonographer-driven” protocol, contrast studies represented 7% to 8% of the total number of routine transthoracic and stress studies. Stress studies accounted for only 15% of the total number of contrast studies. Obesity was the most common indication for contrast use. LV visualization indices and wall thickening assessment, as evaluated by 2 blinded readers, were significantly improved with CE compared with second harmonic imaging alone. The time to make the decision to use CE and the time taken to administer contrast decreased significantly from the feasibility phase to the established phase (8.3 ± 5 vs 7.6 ± 5 min, P < .01, and 13.4 ± 10 vs 10.2 ± 5 min, P < .001, respectively). On the basis of time use only, a cost analysis indicated that savings were obtained at a 10-minute reduction in study time. Conclusions A “sonographer-driven” CE protocol for LV assessment is feasible in high-volume echocardiography laboratories. It is clinically effective because it significantly improves LV global and regional wall motion visualization. A “sonographer-driven” CE protocol can reduce decision and administration times substantially, thus making CE time-efficient. (Am Heart J 2003;145:535-41.)