Antibody-directed enzyme prodrug therapy (ADEPT)

A conjugate of the bacterial enzyme carboxypeptidase G2 and the F(ab)(2) fragment of the anti-CEA monoclonal antibody A5B7 was directed in vitro at the human colon tumour cell line LS174T and the human non-small cell lung line COR-L23. Indirect immunofluorescence microscopy was used to show that the conjugate bound to LS174T cells but not to COR-L23. The cytotoxicity generated by addition of a phenol mustard prodrug to each cell line after pre-incubation with conjugate was found to be significantly greater for LS174T cells (IC50=0.24 mu M) than COR-L23 cells (IC50=108 mu M). However, for a 1:1 mixture of these cells an IC50, of 3.4 mu M was obtained. These data show that phenol mustard released by a localised conjugate can exert a bystander effect on neighbouring cells to which the conjugate does not bind.     

The Relationship Between Gun Ownership and Stranger and Nonstranger Firearm Homicide Rates in the United States, 1981–2010

Objectives. We examined the relationship between gun ownership and stranger versus nonstranger homicide rates.Methods. Using data from the Supplemental Homicide Reports of the Federal Bureau of Investigation’s Uniform Crime Reports for all 50 states for 1981 to 2010, we modeled stranger and nonstranger homicide rates as a function of state-level gun ownership, measured by a proxy, controlling for potential confounders. We used a negative binomial regression model with fixed effects for year, accounting for clustering of observations among states by using generalized estimating equations.Results. We found no robust, statistically significant correlation between gun ownership and stranger firearm homicide rates. However, we found a positive and significant association between gun ownership and nonstranger firearm homicide rates. The incidence rate ratio for nonstranger firearm homicide rate associated with gun ownership was 1.014 (95% confidence interval = 1.009, 1.019).Conclusions. Our findings challenge the argument that gun ownership deters violent crime, in particular, homicides.Firearms cause more than 31 000 deaths annually in the United States.1 Since the tragic shooting of 20 children and 7 adults in Newtown, Connecticut, in 2012, several states have enacted or debated legislation to restrict the availability of firearms.2 Some gun rights advocates have argued that restricting the availability of guns might cause harm by removing an effective deterrent to crime.3-5 Lott, for example, has suggested that reducing the number of guns held by law-abiding citizens might increase homicides because “it would be easier for criminals to prey on the weakest citizens, who would find it more difficult to defend themselves.”5^(p11) Understanding whether increased gun ownership increases or decreases homicides is essential to inform public policy regarding measures to address firearm violence.Of particular interest is the question of whether higher gun ownership is associated with lower rates of stranger homicide (i.e., homicide committed by a person unknown to the victim) because such a relationship is consistent with the hypothesis that increased household ownership of guns deters violent crime by strangers who might otherwise have killed the potential victim.Multiple cross-sectional studies have demonstrated a correlation between higher gun ownership at the state level and higher overall state-specific rates of firearm homicide.6-18 Most recently, we reported a strong and robust relationship between estimated gun ownership in the 50 states and firearm homicide rates over the period 1981 to 2010, while controlling for 20 potential state-level confounding variables.19 None of these studies distinguished between stranger and nonstranger homicides. We are not aware of any published studies that have examined the relationship between gun ownership and stranger versus nonstranger homicide rates.Although the US Department of Justice regularly provides national statistics on rates of stranger versus nonstranger homicide,20,21 we are aware of no published studies that report state-specific data on stranger versus nonstranger homicide. Understanding state-specific patterns of victimization in terms of the relationship between homicide victims and offenders, and identifying the trends in these patterns, would inform state efforts to reduce homicide rates.22Several studies have examined the relationship between homicide victims and offenders in specific settings, such as national youth homicides22; national homicides23,24; Allegheny County, Pennsylvania, homicides25; adolescent homicides in North Carolina26; homicides in Contra Costa County, California27; and national homicides among intimate partners.28 Nationally, between 1980 and 2008, of the homicides for which the relationship between victim and offender was known (63.1% of all homicides), approximately one fifth (21.9%) were stranger homicides.20 We are not aware of any published data on how this may vary among states.In this article, we report and analyze stranger and nonstranger homicides at the state level during the period 1981 to 2010 and examine the relationship between those rates and state-specific household gun ownership during the same years. To the best of our knowledge, ours is the first study to report state-specific data on stranger and nonstranger homicide rates and examine the relationship between state-level gun ownership and stranger and nonstranger homicide rates, while controlling for differences in a wide range of state-level factors associated with homicide.     

The patient as 'teacher': learning in the care of elderly persons with dementia

In 1996 HM Queen Silvia of Sweden started a non-governmental education programme with an integrated day-care unit devoted to elderly persons with dementia. A total of 18 Licensed Practical Nurses (LPN) from various parts of Sweden took part in the year theoretical and practical education in dementia care. The purpose was to develop specialized skills in the particular field and more generally to develop mentor capabilities. The aim of the study was to examine the experiences of the trainees, gained from following a single patient during their entire practical training period in the school's integrated day-care unit. The study was based on a combination of participant observations, interviews, diaries and recorded data and used an ethnographic approach. The results showed that themes such as 'personal guide', 'creating a relationship', 'reducing the working pace' and 'investigative mealtimes' were of major importance for the trainees' learning. In their role as 'personal guides', the trainees fell into six categories with different educational focuses. In their relationships with the patients, the trainees were able to form their own impressions of the patients' present and former lives. By training their ability to adapt the pace at which they worked, they had time to observe symptoms and be aware of the patients' needs, as well as the patients' signs of appreciation. The results also indicated that 'investigative mealtimes' can be an important element in the trainee's education in dementia care.     

Usefulness of tumor volumetry by magnetic resonance imaging in assessing response to radiation therapy in carcinoma of the uterine cervix

: Clinical evaluation of tumor size in cervical cancer is often difficult, and clinical signs of radiation therapy failure may not be present until well after completion of treatment. The purpose of this study is to investigate early indicators of treatment response using magnetic resonance (MR) imaging for quantitative assessment of tumor volume and tumor regression rate before, during, and after radiation therapy.

: Thirty-four patients with cervical cancer Stages IB [5], IIB [8], IIIA [1], IIIB [14], IVA [3], IVB [1], and recurrent [2] were studied prospectively with four serial MR examinations obtained at the start of radiation therapy, at 2-2.5 weeks (20–24 Gy), at 4–5 weeks (40–50 Gy), and 1–2 months after treatment completion. Tumor volume was assessed by three-dimensional volumetric measurements using T₂-weighted images of each MR examination. The volume regression rate was generated based on the four sequential MR studies. These findings were correlated with local control, metastasis rate, and disease-free survival. Median follow-up was 18 months (range: 9–43 months).

: The tumor regression rate after a dose of 40–50 Gy correlated significantly with treatment outcome. The actuarial 2-year disease-free survival was 88.4% in patients with tumors regressing to <20% of the initial volume compared with 45.4% in those with ≥20% residual (p = 0.007). The incidence of local recurrence was 9.5% (2 out of 21) and 76.9% (10 out of 13), respectively (p < 0.001). Analysis by initial tumor volume showed that this observation was valid in patients with initial volumes between 40 and 100 cm³. Analysis by FIGO stage confirmed this observation in all patients except those with Stage IB.

: Sequential tumor volumetry using MR imaging appears to be a sensitive measure of the responsiveness of cervical cancer to irradiation. Treatment response can be assessed as early as during the course of radiation therapy by measurement of initial tumor volume and regression rate at 40–50 Gy. In patients with large (>40 cm³) and advanced (Stage ≥ IIIA) tumors, this technique may be helpful in supplementing the clinical examination for response assessment. The identification of patients at high risk for treatment failure may ultimately lead to improved clinical outcome.     

Prevalence of gonococcal and chlamydial infections and sexual risk behavior among youth in Addis Ababa,Ethiopia

BACKGROUND: No community-based study on the magnitude of sexually transmitted diseases (STDs) has ever been conducted among young people in Ethiopia. GOAL: To assess the magnitude of Chlamydia trachomatis and Neisseria gonorrhoeae infections and status of sexual risk behavior among youths (15-24 years old) in Addis Ababa, Ethiopia. STUDY DESIGN: Youths in or out of school residing in two (of the six) administrative zones in Addis Ababa served as the study population. Participants filled out a self-administered questionnaire related to sexuality and its sociocultural determinants. First-void urine (FVU) was analyzed for gonorrhea and chlamydial infection by polymerase chain reaction (PCR). RESULTS: A total of 561 youths took part in the study. Urine PCR was performed for 522 of them. Nine subjects (1.7%) were found to have and N gonorrhoeae and C trachomatis infections. There were five cases (1.0%) involving each agent. Double infection was noted in one female subject. All but one of the infections were detected among the out-of-school youths (chi-square = 4.5; < 0.05). None of these subjects complained of symptoms suggestive of an active STD. One-third (188/561) reported having had sexual intercourse. The prevalence among sexually active youths was thus 4.8% (9/188) for both infections combined (2.7% for each agent). While 7/52 (13.5%) of the sexually active females were found to also have STDs, only 2/136 (1.5%) of the males had an STD (chi-square = 8.0; < 0.01). Report of sexual activity was significantly associated with being male, an age of >/=20 years, out-of-school status, and report of alcohol/khat (amphetamine-like substance) consumption. Females reported less condom use, whether they were in or out of school and independent of age. CONCLUSIONS: Out-of-school youths, especially females, took more sexual risk and were exceedingly susceptible to STDs. This calls for alternative group-targeted strategies for sex education, disease prevention, and STD screening and management.     

On the Closing Sounds of a Mechanical Heart Valve

In the 1994 Replacement Heart Valve Guidance of the U.S. Food and Drug Administration (FDA), in-vitro testing is required to evaluate the potential for cavitation damage of a mechanical heart valve (MHV). To fulfill this requirement, the stroboscopic high-speed imaging method is commonly used to visualize cavitation bubbles at the instant of valve closure. The procedure is expensive; it is also limited because not every cavitation event is detected, thus leaving the possibility of missing the whole cavitation process. As an alternative, some researchers have suggested an acoustic cavitation-detection method, based on the observation that cavitation noise has a broadband spectrum. In practice, however, it is difficult to differentiate between cavitation noise and the valve closing sound, which may also contain high-frequency components. In the present study, the frequency characteristics of the closing sound in air of a Björk-Shiley Convexo-Concave (BSCC) valve are investigated. The occluder closing speed is used as a control parameter, which is measured via a laser sweeping technique. It is found that for the BSCC valve tested, the distribution of the sound energy over its frequency domain changes at different valve closing speeds, but the cut-off frequency remains unchanged at 123.32± 6.12 kHz. The resonant frequencies of the occluder are also identified from the valve closing sound.     

An evaluation of extubation failure predictors in mechanically ventilated infants and children

OBJECTIVE: To assess the accuracy of traditional weaning indices in predicting extubation failure, and to compare their accuracy when indices are measured at the onset of a breathing trial (SBT) and at the end of the SBT before extubation. DESIGN: Prospective study. SETTING: Medical-surgical intensive care unit at a tertiary care hospital. PATIENTS: Four hundred eighteen consecutive infants and children who received mechanical ventilation for at least 48 h and were deemed ready to undergo a SBT by their primary physician. INTERVENTIONS: Respiratory frequency (RR), tidal volume (V(T)), maximal inspiratory pressure (P(imax)) and frequency-to-tidal volume ratio (f/V(T)) were obtained within the first 5 min of breathing through a T-piece. The primary physicians were unaware of those measurements and the decision to extubate a patient was made by them. RR, V(T), f/V(T) were remeasured before extubation by the respiratory therapists. Extubation failure was defined as needing re intubation within 48 h after extubation. The area under the receiver operating characteristic (ROC) curve was calculated for each index as a measure of the accuracy in predicting extubation outcome. MEASUREMENTS AND MAIN RESULTS: Three hundred twenty-three patients successfully underwent the SBT and were extubated, but 48 of them (14%) required re-intubation. The ROC curve for V(T), RR, P(imax) and f/V(T) measured within the first 5 min of breathing were 0.54, 0.56, 0.57 and 0.57, respectively. The ROC curve did not increase significantly when the above indices were remeasured before extubation. CONCLUSIONS: In a population which had passed SBT, the ability of the traditional weaning indices to discriminate between children successfully extubated and children re-intubated is very poor.     

Innovative testing method for an integrated radiology-histology curriculum

A module of radiology instruction was incorporated into an existing histology course for first-year medical students (n = 177). An innovative testing methodology for assessing the instructional effectiveness of the integrated radiology-histology module was developed and tested. Test items were designed to measure the students' ability to integrate the two disciplines successfully. Radiologic and histologic images were displayed at each of seven stations, to which the content of the images either were or were not related. The seven stations were incorporated into three traditional histology laboratory examinations. For purposes of data analysis, each test was divided into three components, including histology alone, histology in combination, and radiology in combination. Testing lengths were equated using the Spearman-Brown statistical adjustment. Analysis of the test results showed the reliability coefficients to be comparable to the traditional testing methods used previously in the course. Correct responses were similar in all three sections, ranging between 85 to 97%. This methodology thus appears to be an effective means of testing an integrated curriculum.     

Light therapy and advanced wound care for a neuropathic plantar ulcer on a Charcot foot

Light therapy is a relatively novel modality in wound care. I used a light-emitting diode (LED) and superluminous diode (SLD) to deliver low-intensity laser light as an adjunctive treatment to a patient with a chronic diabetic foot ulcer. Standard treatment of conservative sharp debridement, off-loading, bioburden management, and advanced dressings was delivered in a WOC clinic setting. This combination of therapies resulted in closure of the neuropathic plantar ulcer within 8 weeks.