Cytogenetic Heterogeneity in Chronic Lymphocytic Leukemia.

OBJECTIVES: Chronic lymphocytic leukemia (CLL) is a malignancy identified by an increase in the number of lymphocytes in the blood. It is one of the most common adult leukemias. It is a heterogeneous clinical disease with changeable progression. Chromosomal aberrations play a significant role in predicting clinical outcomes and survival. Treatment strategies for each patient are determined by chromosomal abnormalities. Cytogenetic methods are sensitive procedures for detecting abnormalities in the genome. The aim of this study was to document the incidence of different genes and gene rearrangements in CLL patients by comparing conventional cytogenetic and fluorescence in situ hybridization (FISH) results and predicting their prognosis. Materials and Methods A total of 23 CLL patients, 18 men and five women with ages ranging from 45-75 years were enrolled in this case series. Interphase fluorescent in situ hybridization (I-FISH) was conducted on peripheral blood or bone marrow samples, whichever were available, and were cultured in growth culture medium. I-FISH was used to detect chromosomal abnormalities such as 11q-, del13q14, 17p-, 6q- and trisomy 12 in CLL patients. Results FISH results showed that there were different chromosomal gene rearrangements including del13q, del17p, del6q, del11q, and trisomy 12. Recurrent chromosomal abnormalities involved trisomy 12, del17p, del13q and novel translocation (8;17) were only seen in one patient. Conclusion Genomic aberrations in CLL are important independent predictors of disease progression and survival. Interphase cytogenetic analysis using FISH revealed chromosomal changes in the majority of CLL samples and is superior to standard karyotype analysis for identifying cytogenetic abnormalities.

Assessment of PTEN Gene Loss as a Possible Prognostic Marker for Prostate Cancer.

OBJECTIVES: Background: Prostate Cancer (PCa) is a leading cause of cancer deaths in older men worldwide. In the phosphatidylinositol 3-kinase (PIK3)/AKT pathway, the PTEN (10q23.3) gene is a negative regulator and a tumor suppressor gene frequently deleted in PCa. Information about the PTEN deletion in the primary tumor, in addition to clinico-pathological parameters, might be of significance for selecting the ideal treatment for a patient. Therefore, the aim of the present study was to determine the frequency of PTEN deletion in prostate cancer using FISH technique. Materials and Method: Histopathologically proven and diagnosed PCa patients were included for a PTEN gene deletion study by FISH technique. FISH was performed on paraffin embedded tissue using ZytoLight SPEC PTEN/CEN10 Dual Color Probe Kit (CytoVision GmbH, Bremerhaven, Germany). Results: A total of 42 histopathologically proven and diagnosed PCa patients were enrolled in the present study. The median age was 65 years. PTEN gene deletion was positive in 24 patients (57%) while 18 (43%) were negative. PTEN gene deletion was significantly higher in advanced stages as compared to those in early advanced stages. PTEN gene was significantly deleted in patients with the presence of positive lymph nodes compared to patients without positive lymph nodes. Conclusion: The present study suggests that PTEN deletion is associated with tumor stage and lymph node status. This study demonstrated that a higher rate of PTEN deletion is associated with advanced stage cancers with a Gleason's score of 7, which explains the poor prognosis associated with its deletion. Detection of PTEN status will help to identify the specific subsets of patients who might benefit from molecular targeted therapies.

A Comprehensive Review of Chronic Myeloid Leukemia: An Indian Perspective.

OBJECTIVES: The use of imatinib has brought a standard shift in the management of chronic myeloid leukemia (CML) during the last two decades. In India, imatinib has been available for more than fifteen years and has been made available all over the country due to patient assistance programs and cheaper generic versions. Despite improvements in survival of CML patients, there are unique challenges in the Indian context. Indian patients present with more advanced disease. Most centers have access to imatinib as first-line therapy, but there is limited availability of molecular monitoring and second-line therapy. Most of the outcome data is retrospective and comparable with that reported in Western centers. Drug adherence is impaired in at least one third of patients and contributes to poor survival. The aim of this review is to highlight the fact that prospective studies and cooperative studies are very much needed to improve the quality of data available on Indian CML patients.

Clinical Implications of Simultaneous Occurrence of Variant Philadelphia Translocations in Chronic Myeloid Leukemia.

OBJECTIVES: Up to 90% of cases of chronic myeloid leukemia (CML) are myeloproliferative disorders characterized by a Philadelphia (Ph) chromosome with a classical t(9;22)(q34;q11). Of all CML patients, 5-10% show variant Philadelphia translocations (vPh) and are an area of research interest for their significance in predicting response to various therapies, including tyrosine kinase inhibitors. They are also being studied for prognosticating multi-year survival outcomes in varied patient populations, with conflicting results. We included 238 patients for conventional cytogenetic and fluorescence in situ hybridization study from January 2018 to October 2018. Patients with vPh in CML-Chronic Phase (CML-CP) were analyzed with respect to their demographic parameters, response to imatinib therapy, and survival. Out of 238 patients diagnosed with CML-CP, 8 patients (3.3%) showed vPh. The most common chromosomes involved in these translocations were 1, 2, 3, 4, 7, 11 and 12. In almost all the cases with variant Ph chromosome, the BCR-ABL rearrangement was detected by molecular methods or by fluorescence in situ hybridization (FISH). All patients were treated with imatinib as a first-line therapy. Rates of complete hematological response, complete cytogenetic response, and major molecular response were similar in all patients with classical Ph and variant Ph chromosome. Our data suggest that prognosis of CML patients with vPh in CML has no significant effect in predicting response to imatinib or in predicting survival.

Association between α1-antitrypsin and bronchiectasis in patients with humoral immunodeficiency receiving gammaglobulin infusions.

BACKGROUND: In patients with humoral immunodeficiency, the progression of bronchiectasis has been known to occur despite adequate gammaglobulin therapy and in the absence of recurrent infections. This observation suggests that factors other than gammaglobulin replacement might play a part in the prevention of lung damage in this population. α1-Antitrypsin deficiency can be associated with bronchiectasis, a chronic inflammatory lung disease. The protective levels of α1-antitrypsin and phenotype in preventing bronchiectasis have not been thoroughly studied in the immunodeficient population. We hypothesized that patients with humoral immunodeficiencies on gammaglobulin infusions and bronchiectasis have lower median levels, but not necessary "classically" deficient levels, of α1-antitrypsin compared with those without bronchiectasis. OBJECTIVE: To compare levels of α1-antitrypsin in subjects with immunodeficiency with and without bronchiectasis. METHODS: One hundred ninety-two subjects with humoral immunodeficiencies requiring gammaglobulin therapy had their α1-antitrypsin levels and phenotype screened. High-resolution computed tomograms of the chest of participants were obtained and compared with α1-antitrypsin levels and phenotype. RESULTS: Participants without bronchiectasis were found to have higher median levels of α1-antitrypsin than those with bronchiectasis (P = .003). Furthermore, subjects with improving or resolved bronchiectasis since initiating gammaglobulin therapy had higher median levels of α1-antitrypsin than those with worsening bronchiectasis (P = .004). The prevalence of the α1-antitrypsin PiZZ mutation was higher than in the general public (P < .0001). CONCLUSION: Median α1-antitrypsin levels and phenotype in subjects were associated with humoral immunodeficiency and their bronchiectasis status. Prospective studies might be necessary to determine possible benefits of augmentation therapy. This study supports the idea that what is considered a "normal or protective" α1-antitrypsin range might need to be refined for patients with humoral immunodeficiency on gammaglobulin therapy.

Scholar 7: The Development of Regional Community Hospitals' Scholastic Environment.

The importance of increasing scholarly activity has been highlighted among residency programs currently accredited by the American Osteopathic Association (AOA) to ensure a smooth transition to the single accreditation system. The Scholar 7 program, a series of seven 2-hour sessions, was created to aid faculty and residents in the pursuit of scholarly work and to facilitate change in an entire community hospital system's environment by creating a self-replicating scholarly culture in a timely and cost-efficient manner. Skills were taught by means of preparation and submission of a research protocol to the institutional review board (IRB) along with grant proposals. The authors tracked scholarly work, IRB submissions, and grants awarded to participants during the 2015-2016 academic year. The results were compared in a post-hoc fashion with previous classes since 2007-2008 within the same hospitals system. The Scholar 7 program successfully aided faculty in achieving their required pursuit of scholarly work in 8 months. This program has the potential to help AOA-focused residency programs meet the scholarly requirements of the Accreditation Council for Graduate Medical Education.

Reducing Errors in Transition from Acute Stroke Hospitalization to Inpatient Rehabilitation.

OBJECTIVE: Effective stroke care does not end with acute treatment during hospitalization, but extends through rehabilitation and secondary stroke prevention. In transitions across care environments, stroke patients are vulnerable to errors in communication of diagnosis and treatment. This study aimed to demonstrate that formalized communication between the neurology team and the rehabilitation medicine team would promote secondary stroke prevention and minimize interruptions during rehabilitation. METHODS: The intervention was a standardized verbal handoff by phone between the discharging neurology resident and the admitting rehabilitation resident regarding each patient at transfer. This retrospective cohort study compared a pre-intervention control group (September 2012 to February 2013) and a post-intervention group transferred with the handoff (September 2013 to January 2014). The outcomes measured included errors in communication of stroke severity, stroke mechanism, medications, and recommended follow-up (appointments and tests) as well as emergent brain imaging, return to the acute care facility, and readmission. RESULTS: The pre- and post-intervention groups were similar with respect to number of patients (50 vs. 52) and demographics including gender (52 vs. 54% female), age (65.8 vs. 64.0 years), severity of illness as measured by the National Institutes of Health Stroke Scale (NIHSS) (10 vs. 6.5), and stroke type (84 vs. 77% ischemic). Implementation of the handoff decreased errors in communication of diagnosis (NIHSS 92 vs. 74%, p = 0.02; stroke mechanism 54 vs. 30%, p = 0.02). Furthermore, the handoff decreased the proportion with errors in reconciliation of critical medications (42 vs. 23%, p = 0.04). However, the intervention did not significantly reduce interruptions of the rehabilitation program, such as emergent brain imaging (8 vs. 12%, p = 0.55), or transfers back to the acute care hospital (26 vs. 21%, p = 0.56). CONCLUSION: Standardized handoffs decreased errors in communication of diagnosis and critical medications for secondary stroke prevention.

Genetic vs Environmental Factors That Correlate With Rosacea: A Cohort-Based Survey of Twins.

IMPORTANCE: To our knowledge, this is the first study on rosacea to formally define genetic and environmental contributions. OBJECTIVES: To study a cohort of identical and fraternal twins to determine whether genetic factors contribute to rosacea development and, if genetic factors are present, quantitatively estimate the genetic contribution, as well as to identify environmental factors that correlate with rosacea by controlling for genetic susceptibility. DESIGN, SETTING, AND PARTICIPANTS: Identical and fraternal twins were surveyed regarding risk factors implicated in rosacea. Faculty dermatologists determined a rosacea score for each twin participant according to the National Rosacea Society (NRS) grading system. Data were collected at the annual Twins Days Festival in Twinsburg, Ohio, on August 4-5, 2012, and August 2-3, 2013. Analysis was conducted for several months after each meeting. A cohort of 550 twin individuals, with most from Ohio, Pennsylvania, and the northeastern United States, participated. MAIN OUTCOMES AND MEASURES: The NRS score and rosacea subtype were assessed using the NRS grading system and physical examination by board-certified dermatologists. RESULTS: Among the 275 twin pairs (550 individuals), there were 233 identical twin pairs with a mean rosacea score of 2.46 and 42 fraternal twin pairs with a mean rosacea score of 0.75. We observed a higher association of NRS scores between identical vs fraternal twins (r = 0.69 vs r = 0.46; P = .04), demonstrating a genetic contribution. Using the ACE model (proportion of variance in a trait heritable secondary to additive genetics [A] vs the proportions due to a common environment [C] and unique environment [E]), we calculated this genetic contribution to be 46%. A higher NRS score was also significantly associated with the following factors: age (r = 0.38; P < .001) and lifetime UV radiation exposure (r = 0.26; P < .001). These associations remained after use of propensity score matching to adjust for multicollinearity. Other correlated variables included body mass index (r = 0.21; P < .001), smoking (r = 0.10; P < .02), alcohol consumption (r = 0.11; P = .01), cardiovascular comorbidity (r = 0.17; P < .001), and skin cancer comorbidity (r = 0.19; P < .001). CONCLUSIONS AND RELEVANCE: The study of twins allows us to separate genetic susceptibility and the influence of environmental factors affecting rosacea. We found that approximately half of the contribution to the NRS score could be accounted for by genetics and the other half by environment. We identified correlations between rosacea and UV radiation exposure, alcohol, smoking, skin cancer history, cardiac comorbidity, and age. These findings may help improve current management and expectations of individuals affected by rosacea.

Epidemiology of limb loss.

In 2005, 1.6 million people were estimated to be living with limb loss; by 2050, the rate is expected to double to 3.6 million in the United States. Past data have shown that the rates of dysvascular amputations were increasing. However, recent studies looking at single diseases of peripheral arterial disease and diabetes mellitus show amputations related to these conditions are now decreasing. The authors think that it may not be a single disease process but rather the cumulative illness burden that is leading to amputations. In addition to cause, age, gender, and race continue to play a role in limb loss.

Former heroin addicts with or without a history of cocaine dependence are more impulsive than controls.

BACKGROUND: Personality traits such as impulsivity and sensation seeking may contribute to the initiation and maintenance of illicit drug use. Since studies have reported higher impulsivity and sensation seeking traits in cocaine dependent subjects, we were interested in determining whether former heroin addicts in methadone pharmacotherapy with comorbid cocaine addiction have greater impulsivity than those without. METHODS: Instruments to assess impulsivity (Barratt Impulsiveness Scale version 11) and sensation seeking (Sensation Seeking Scale version V) were administered to former severe heroin addicts meeting Federal criteria for methadone maintenance pharmacotherapy with (n = 71) or without cocaine dependence (n = 31) and to 145 normal healthy (non-methadone-maintained) volunteers. RESULTS: The methadone-maintained without cocaine dependence and the methadone-maintained with cocaine dependence groups, both scored higher than did the normal volunteer group on the Barratt Impulsiveness Scale total score (p<0.001). On the Barratt Impulsiveness Scale Attentional, Nonplanning, and Motor subscales, the methadone-maintained and methadone-maintained with cocaine dependence groups scored higher than did normal volunteers with no history of drug abuse or dependence (p<0.001). There was no difference among groups on total score or any subscale of the Sensation Seeking Scale. However, males in all groups overall scored higher than did females on Disinhibition and Thrill and Adventure seeking subscales of the Sensation Seeking Scale version V (p<0.001). CONCLUSIONS: This study demonstrates higher impulsivity in former severe heroin addicts meeting criteria for or currently in stable methadone maintenance pharmacotherapy, irrespective of a positive or negative history of cocaine dependence.

Penetrating eyelid injury: a case report and review of literature.

INTRODUCTION: In literature, many different types of foreign objects have been found to have caused eye injuries. These objects can range from organic to inorganic matter such as glass, wood, pencil, nails and fishhooks. Once the injury is recognized, removal of the foreign body and technique used in the management of the injury is very important to reduce further ocular damage. This case report investigates an injury caused by an object similar to a fishhook that pierced into the eyelid in the opposite direction to normal. CASE PRESENTATION: A 19 year old man presented with a one hour history of the right upper eyelid injury from a wire fence. The loose end of the wire penetrated the full thickness of the eyelid in the direction opposite to the normal. The wire passed from under the eyelid, through the centre of the upper lid, to the external surface. After the application of topical anesthetic drops, the eye could be opened manually, the lid averted, and the wire passed out through the defect. No complications were observed. Post removal, the acuity increased to 6/9 and there was no intraocular penetration. Full recovery was observed as well. CONCLUSION: A severe eyelid penetrating injury can be uncomplicated with a full recovery when there is no intraocular penetration. It is also possible to have an injury pass under the lower margin of the lid and penetrate from inside to out, with no associated corneal injury.

Infrared matrix isolation study of the thermal and photochemical reactions of ozone with dimethylzinc.

The matrix isolation technique has been combined with infrared spectroscopy and theoretical calculations to explore the reaction of (CH3)2Zn with O3 over a range of time scales. Upon twin jet deposition, an initial cage pair complex was observed, along with formation of the novel H3COZnCH3 species. Subsequent UV irradiation destroyed the complex and greatly increased the yield of H3COZnCH3. An extensive set of bands were seen for this molecule, and (18)O spectroscopic data were obtained as well. The identification of this species was supported by theoretical calculations at the B3LYP/6-311++g(d,2p) level. Merged jet deposition led to a very different set of products, including H2CO, CH3OH and C2H6, identifications that were confirmed by (18)O substitution. In addition, a new variable length concentric deposition technique was developed to permit study of the time scales between twin (relatively short) and merged (relatively longer) reaction times. Mechanistic inferences for this reaction are discussed.

Pharmaceuticals: pharmaceutical cost controls--2005. End of Year Issue Brief.

The enactment of the Omnibus Budget Reconciliation Act of 1990 (OBRA '90) gave states the option of offering pharmaceutical benefits within their Medicaid programs. But the law placed restrictions on states' flexibility to control what prescriptions they would cover and required the states to reimburse outpatient prescription drugs from manufacturers that signed rebate agreements with the U.S. Department of Health and Human Services. Forty-nine states--Arizona is excluded, based on its program structure--and the District of Columbia currently offer prescription drug coverage under the Medicaid Drug Rebate Program. During the past four years, states all over the country have been plagued with revenue shortfalls in their state Medicaid budgets. While the fiscal situation improved for most states in the 2004 legislative session, many states still face budget pressures in 2005. Compounding existing budget pressures are threats from the Bush Administration to shift increased costs of the Medicaid program on to the states. All things considered, the economic pressure of funding Medicaid is at the top of legislative agendas in 2005. As in previous years, states are attempting to reduce costs to their Medicaid programs by seeking savings in their pharmaceutical programs. Prescription drug costs are highly attributed as a contributing factor to the fiscal climate of state Medicaid programs. Currently, prescription drug spending outpaces that of every other category of health care and drug prices are rising faster than inflation. In response, states are instituting a variety of pharmaceutical cost control measures such as creating preferred drug lists (PDLs), negotiating supplemental rebates, forming bulk purchasing pools, promoting generic drug substitution and implementing price controls. As prescription drug cost containment tools have gained acceptance and momentum, they continue to be controversial. This issue brief explores the debate, history, methodology, utilization and 2005 legislative activity surrounding the most commonly used and emerging pharmaceutical cost control measures.

Public health issue brief: medical marijuana: year end report-2004.

During the last few years, the debate over the use of marijuana for medical purposes has moved from the legislative arena into the public forum. Thirty six states and the District of Columbia have had statutes that address the medical utility of marijuana within the past 26 years. However, several of those states have either repealed the laws or allowed them to sunset. Since 1996, 11 states have enacted laws that allow individuals to use marijuana with a doctor's consent.