Biomedical subjects

J Rosen

Publications and source records attributed to J Rosen.

At least 19 recordsLinked to original sources

PubMed2004

Necrotizing meningoencephalitis and pneumonitis in a simian immunodeficiency virus-infected rhesus macaque due to Acanthamoeba.

Free-living amoebae of the genus Acanthamoeba can cause a fatal disease of the brain in humans called granulomatous amoebic encephalitis. We present a case of meningoencephalitis and pneumonitis in a simian immunodeficiency virus (SIV)-infected rhesus macaque caused by Acanthamoeba sp. The animal became ill 176 days after intravenous inoculation with SIVmac251 after a short history of weight loss and a sudden onset of hind limb paresis and abnormal head movements. Histopathologic examination of hematoxylin and eosin-stained tissues revealed multifocal to coalescing necrotizing neutrophilic meningoencephalitis and pneumonitis. Immunofluorescence and polymerase chain reaction were used to identify the genus of amoeba as Acanthamoeba. Immunohistochemistry of immune cell markers was used to characterize the animal's immune response to the opportunistic amoebic infection with features of both innate and adaptive cell-mediated immunity. Although not previously reported, the potential transmission to humans, either through environmental contamination or contact with an infected animal, makes this disease a threat to laboratory animal care staff and pathologists.

Acanthamoeba↗

PubMed2002

Assessment of behavioral and psychological symptoms of dementia.

In spite of their prevalence and persistence, why are behavioral and psychological symptoms of dementia difficult for clinicians to assess and manage? This paper provides an overview of the methodological challenges encountered in measuring behavioral disturbances of dementia. Specifically, conceptual constructs of behavioral and psychological symptoms of dementia, the strengths and weaknesses of the currently existing rating instruments, analytic methodologies, and the utility of technological devices are outlined in the service of formulating future directions in behavioral and psychological symptoms of dementia assessment research.

Journal Article↗

PubMed2002

Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile.

A novel approach to the treatment of osteoporosis in men, and possibly women, is the development of selective androgen receptor modulators (SARMs) that can stimulate formation of new bone with substantially diminished proliferative activity in the prostate, as well as reduced virilizing activity in women. Over the last several years, we have developed a program to discover and develop novel, non-steroidal, orally-active selective androgen receptor modulators (SARMs) that provide improved therapeutic benefits and reduce risk and side effects. In recent studies, we have used a skeletally mature orchiectomized (ORX) male rat as an animal model of male hypogonadism for assessing the efficacy of LGD2226, a nonsteroidal, non-aromatizable, and non-5alpha-reducible SARM. We assessed the activity of LGD2226 on bone turnover, bone mass and bone strength, and also evaluated the effects exerted on classic androgen-dependent targets, such as prostate, seminal vesicles and muscle. A substantial loss of bone density was observed in ORX animals, and this loss was prevented by SARMs, as well as standard androgens. Biochemical markers of bone turnover revealed an early increase of bone resorption in androgen-deficient rats that was repressed in ORX animals treated with the oral SARM, LGD2226, during a 4-month treatment period. Differences in architectural properties and bone strength were detected by histomorphometric and mechanical analyses, demonstrating beneficial effects of LGD2226 on bone quality in androgen-deficient rats. Histomorphometric analysis of cortical bone revealed distinct anabolic activity of LGD2226 in periosteal bone. LGD2226 was able to prevent bone loss and maintain bone quality in ORX rats by stimulating bone formation, while also inhibiting bone turnover. LGD2226 also exerted anabolic activity on the levator ani muscle. Taken together, these results suggest that orally-active, non-steroidal SARMs may be useful therapeutics for both muscle and bone in elderly hypogonadal men through their anabolic activities. Since SARMs both prevent bone loss, and also stimulate formation of new bone, they may have significant advantages relative to currently used anti-resorptive therapies. Coupled with their activity in muscle and their ability to maintain or restore libido, they offer new therapeutic approaches for male and female hormone replacement.

Journal Article↗

PubMed2001

Hydrazinonaphthalene and azonaphthalene thrombopoietin mimics are nonpeptidyl promoters of megakaryocytopoiesis.

High-throughput screening for the induction of a luciferase reporter gene in a thrombopoietin (TPO)-responsive cell line resulted in the identification of 4-diazo-3-hydroxy-1-naphthalenesulfonic acids as TPO mimics. Modification of the core structure and adjustment of unwanted functionality resulted in the development of (5-oxo-1,5-dihydropyrazol-4-ylidene)hydrazines which exhibited efficacies equivalent to those of TPO in several cell-based assays designed to measure thrombopoietic activity. Furthermore, these compounds elicited biochemical responses in TPO-receptor-expressing cells similar to those in TPO itself, including kinase activation and protein phosphorylation. Potencies for the best compounds were high for such low molecular weight compounds (MW < 500) with EC(50) values in the region of 1-20 nM.

Animals↗

PubMed2001

The 5-HTTPRS/L polymorphism and aggressive behavior in Alzheimer disease.

BACKGROUND: Aggressive behavior in Alzheimer disease (AD) has been linked to dysfunction of serotonin neurotransmission. Homozygosity for the long variant (*L) of an identified biallelic polymorphism of the serotonin transporter promoter region (5-HTTPR) is associated with increased expression of the transporter protein and increased speed of response to serotonin reuptake inhibitor treatment. OBJECTIVE: To determine whether the *L/*L genotype and the *L allele are associated with an increased risk of aggressive symptoms in patients with AD. DESIGN: Case-control study. SETTING: University hospital geriatric psychiatry inpatient program and Alzheimer disease research center. SUBJECTS: Fifty-eight patients with AD with a history of aggressive behavior and 79 never-aggressive patients with AD with comparable severity of cognitive impairment. MAIN OUTCOME MEASURES: The 5-HTTPR genotype and allele frequency. RESULTS: The *L/*L genotype was significantly associated with aggression in patients with AD (odds ratio, 2.8; 95% confidence interval, 1.2-6.5). Similar results were obtained for *L allele frequency. CONCLUSION: The 5-HTTPR*L allele and *L/*L genotype may predispose patients with AD to develop aggressive behavior.

Aged↗

PubMed2001

A labor perspective of workplace violence prevention. Identifying research needs.

BACKGROUND: During the past decade, labor unions have contributed to efforts to increase awareness of the importance of workplace violence as an occupational hazard. Research by the National Institute for Occupational Safety and Health and the U.S. Department of Justice have bolstered these efforts. This research revealed that workplace violence is the second leading cause of traumatic-injury death on the job for men, the leading cause of traumatic-injury death on the job for women, and accounts for some 2 million nonfatal injuries each year in the United States. LABOR PERSPECTIVE: Ten years ago, the debate focused on whether workplace violence is an occupational hazard or strictly a police and criminal justice issue. Labor unions have joined with occupational safety and health professionals in recognizing that workplace violence is a serious occupational hazard that is often predictable and preventable. They have advocated that employers establish multidimensional violence-prevention programs. CONCLUSION: Although the nature of workplace violence varies from industry to industry, implementation of the federal Occupational Safety and Health Administration (OSHA) Violence Prevention Guidelines for Health Care and Social Service Workers and for Late-Night Retail Establishments is a high priority to unions in the affected industries. Labor wants employers to invest in protecting workers from violence through voluntary programs and state legislation, and it supports the promulgation of a mandatory federal OSHA standard. To that end, intervention research can play a key role in demonstrating effective, technically and economically feasible prevention strategies

Homicide↗

PubMed2001

The 5-HTTPR polymorphism confers liability to a combined phenotype of psychotic and aggressive behavior in Alzheimer disease.

BACKGROUND: Psychotic symptoms in subjects with Alzheimer disease (AD+psychosis, AD+P) are a marker for a distinct phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors. We recently found that AD subjects homozygous for long alleles (l) of an insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTTPR) had elevated rates of aggressive behavior. OBJECTIVE: To examine whether the 5-HTTPR ll genotype confers an increased risk of AD+P, and of the combined AD+P/aggressive phenotype. METHODS: The 5-HTTPR genotype was determined in 332 subjects diagnosed with possible or probable AD. All subjects received structured psychiatric assessments and were categorized with regard to their history of aggressive behaviors and psychotic symptoms. RESULTS: Consistent with other reports, AD+P was associated with a significant increased risk for aggressive behavior. AD+P and aggression were both significantly associated with 5-HTTPR ll genotype and with an increased l allele frequency. Subjects with the combined behavioral phenotype (AD+P and aggressive behavior) had the highest rate of ll genotype and highest l allele frequency. CONCLUSION: The 5-HTTPR l allele appears to confer risk for the combined AD+P/aggressive phenotype. Confirmation of this association in a similar behaviorally well-characterized independent sample is needed.

Aged↗

PubMed2001

Markov modeling of minimally invasive surgery based on tool/tissue interaction and force/torque signatures for evaluating surgical skills.

The best method of training for laparoscopic surgical skills is controversial. Some advocate observation in the operating room, while others promote animal and simulated models or a combination of surgery-related tasks. A crucial process in surgical education is to evaluate the level of surgical skills. For laparoscopic surgery, skill evaluation is traditionally performed subjectively by experts grading a video of a procedure performed by a student. By its nature, this process uses fuzzy criteria. The objective of the current study was to develop and assess a skill scale using Markov models (MMs). Ten surgeons [five novice surgeons (NS); five expert surgeons (ES)] performed a cholecystectomy and Nissen fundoplication in a porcine model. An instrumented laparoscopic grasper equipped with a three-axis force/torque (F/T) sensor was used to measure the forces/torques at the hand/tool interface synchronized with a video of the tool operative maneuvers. A synthesis of frame-by-frame video analysis and a vector quantization algorithm, allowed to define F/T signatures associated with 14 different types of tool/tissue interactions. The magnitude of F/T applied by NS and ES were significantly different (p < 0.05) and varied based on the task being performed. High F/T magnitudes were applied by NS compared with ES while performing tissue manipulation and vise versa in tasks involved tissue dissection. From each step of the surgical procedures, two MMs were developed representing the performance of three surgeons out of the five in the ES and NS groups. The data obtained by the remaining two surgeons in each group were used for evaluating the performance scale. The final result was a surgical performance index which represented a ratio of statistical similarity between the examined surgeon's MM and the MM of NS and ES. The difference between the performance index value, for a surgeon under study, and the NS/ES boundary, indicated the level of expertise in the surgeon's own group. Using this index, 87.5% of the surgical procedures were correctly classified into the NS and ES groups. The 12.5% of the procedures that were misclassified were performed by the ES and classified as NS. However in these cases the performance index values were very close to the NS/ES boundary. Preliminary data suggest that a performance index based on MM and F/T signatures provides an objective means of distinguishing NS from ES. In addition, this methodology can be further applied to evaluate haptic virtual reality surgical simulators for improving realism in surgical education.

Algorithms↗

PubMed2001

Mechanisms of hormonal prevention of breast cancer.

Reproductive history is a consistent risk factor for human breast cancer. Epidemiological studies have repeatedly demonstrated that early age of first pregnancy is a strong protective factor against breast cancer and provides a physiologically operative model to achieve a practical mode of prevention. In rodents, the effects of full-term pregnancy can be mimicked by a three-week exposure to low doses of estrogen and progesterone. Neither hormone alone is sufficient to induce protection. The cellular and molecular mechanisms that underlie hormone-induced refractoriness are largely unresolved. Our recent studies have demonstrated that an early cellular response that is altered in hormone-treated mammary cells is the initial proliferative burst induced by the chemical carcinogen methylnitrosourea. The decrease in proliferation is also accompanied by a decrease in the ability of estrogen receptor-positive cells to proliferate. RNA expression of several mammary cell-cycle-related genes is not altered in hormone-treated mice; however, immunohistochemical assays demonstrate that the protein level and nuclear compartmentalization of the p53 tumor suppressor gene are markedly upregulated as a consequence of hormone treatment. These results support the hypothesis that hormone stimulation, at a critical period in mammary development, results in cells with persistent changes in the intracellular regulatory loops governing proliferation and response to DNA damage. A corollary to this hypothesis is that the genes affected by estrogen and progesterone are independent of alveolar differentiation-specific genes. Suppressive subtractive hybridization-PCR methods have identified several genes that are differentially expressed as a consequence of prior estrogen and progesterone treatment. Future experiments are aimed at determining the mechanisms of hormone-induced upregulation of p53 protein expression as part of the overall goal of identifying and functionally characterizing the genes responsible for the refractory phenotype.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

A double-blind randomized comparison of nortriptyline plus perphenazine versus nortriptyline plus placebo in the treatment of psychotic depression in late life.

OBJECTIVE: To conduct the first randomized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression. METHOD: The efficacy of nortriptyline plus placebo versus nortriptyline plus perphenazine was compared in 36 patients aged 50 years or older presenting with a major depressive episode with psychotic features (DSM-III-R criteria). Patients were started openly on nortriptyline treatment titrated to therapeutic levels. They were then randomly assigned under double-blind conditions to addition of perphenazine or placebo. Outcomes were compared in the 2 treatment groups using measures including the Hamilton Rating Scale for Depression (HAM-D) and the Brief Psychiatric Rating Scale (BPRS); side effects were assessed with the Geriatric Movement Disorder Assessment. RESULTS: Both treatments were well tolerated. Of the 36 randomly assigned patients, 2 (1 in each group) dropped out due to treatment-related adverse effects. Four additional patients dropped out for administrative reasons. Thirty patients received nortriptyline for at least 4 weeks combined with either perphenazine (N = 14) or placebo (N = 16) for at least 2 weeks (median = 9 weeks). There was no significant difference between the completers in the 2 treatment groups when comparing their scores on the HAM-D, the BPRS, its psychoticism subscale, or any side effects measure. Rates of response (defined as resolution of both depression and psychosis) did not differ significantly in the 2 groups (nortriptyline-plus-perphenazine group, 50% vs. nortriptyline-plus-placebo group, 44%). CONCLUSION: When treating older patients with psychotic depression, the addition of a moderate dose of a traditional neuroleptic to a tricyclic antidepressant was well tolerated but did not improve efficacy. This finding supports existing data suggesting that the pathophysiology (and thus the required treatment) of psychotic depression may be different early and late in life.

Affective Disorders, Psychotic↗

PubMed2001

Therapeutic radiation and the neurosurgeon.

For nearly a century, neurosurgeons have been involved in the use of therapeutic radiation. Long before there was a separate discipline of radiology or radiation therapy, pioneers such as Cushing and Frasier explored the effects of X-rays and radium on patients with brain tumors and arteriovenous malformations. This interest was never completely abandoned and was again pursued with vigor with the emergence of image-guided sterotaxy for use in intracranial brachytherapy and radiosurgery. Neurosurgeons have been and will remain at the forefront of these and other emerging techniques.

Brain Neoplasms↗

PubMed2001

Effects of geared motor characteristics on tactile perception of tissue stiffness.

Endoscopic haptic surgical devices have shown promise in addressing the loss of tactile sensation associated with minimally invasive surgery. However, these devices must be capable of generating forces and torques similar to those applied on the tissue with a standard endoscopic tool. Geared motors are a possible solution for actuation; however, they possess mechanical characteristics that could potentially interfere with tactile perception of tissue qualities. The aim of the current research was to determine how the characteristics of a geared motor suitable for a haptic surgical device affect a user's perception of stiffness. The experiment involved six blindfolded subjects who were asked to discriminate the stiffness of six distinct silicone rubber samples whose mechanical properties are similar to those of soft tissue. Using a novel testing device whose dimensions approximated those of an endoscopic grasper, each subject palpated 30 permutations of sample pairs for each of three types of mechanical loads; the motor (friction and inertia), a flywheel (with the same inertia as motor), and a control (no significant mechanical interference). One factor ANOVA of the error scores and palpation time showed that no significant difference existed among error scores, but mean palpation time for the control was significantly less than for the other two methods. These results indicated that the mechanical characteristics of a geared motor chosen for application in a haptic surgical device did not interfere with the subjects' perception of the silicone samples' stiffness, but these characteristics may significantly affect the energy expenditure and time required for tissue palpation. Therefore, before geared motors can be considered for use in haptic surgical devices, consideration should be given to factors such as palpation speed and fatigue.

Biomechanical Phenomena↗

PubMed2001

MEDNET: a medical simulation network grand challenge.

The need to improve war-fighter training led to significant advancements in simulator technology. Now, simulator technology is ready to be applied to a new challenge: an evolutionary approach to training military medical personnel that will result in improved combat casualty care. With the exception of the introduction of helicopter evacuation support during the Korean War, changes in combat casualty care have not significantly altered the percentage of wounded soldiers lost in combat since World War II. The introduction of battlefield simulator training has improved strategic planning and combat readiness. It is time to apply these same tools to improve medical planning, military medical readiness and execution of casualty care.

Computer Communication Networks↗

PubMed2001

Objective laparoscopic skills assessments of surgical residents using Hidden Markov Models based on haptic information and tool/tissue interactions.

UNLABELLED: Laparoscopic surgical skills evaluation of surgery residents is usually a subjective process, carried out in the operating room by senior surgeons. By its nature, this process is performed using fuzzy criteria. The objective of the current study was to develop and assess an objective laparoscopic surgical skill scale using Hidden Markov Models (HMM) based on haptic information, tool/tissue interactions and visual task decomposition. METHODS: Eight subjects (six surgical trainees: first year surgical residents 2 x R1, third year surgical residents 2 x R3 fifth year surgical residents 2 x R5; and two expert laparoscopic surgeons: 2 x ES) performed laparoscopic cholecystectomy following a specific 7 steps protocol on a pig. An instrumented laparoscopic grasper equipped with a three-axis force/torque sensor located at the proximal end with an additional force sensor located on the handle, was used to measure the forces and torques. The hand/tool interface force/torque data was synchronized with a video of the tool operative maneuvers. A synthesis of frame-by-frame video analysis was used to define 14 different types of tool/tissue interactions, each one associated with unique force/torque (F/T) signatures. HMMs were developed for each subject representing the surgical skills by defining the various tool/tissue interactions as states and the associated F/T signatures as observations. The statistical distance between the HMMs representing residents at different levels of their training and the HMMs of expert surgeons were calculated in order to generate a learning curve of selected steps during laparoscopic cholecystectomy. RESULTS: Comparison of HMM's between groups showed significant differences between all skill levels, supporting the objective definition of a learning curve. The major differences between skill levels were: (i) magnitudes of F/T applied (ii) types of tool/tissue interactions used and the transition between them and (iii) time intervals spent in each tool/tissue interaction and the overall completion time. The objective HMM analysis showed that the greatest difference in performance was between R1 and R3 groups and then decreased as the level of expertise increased, suggesting that significant laparoscopic surgical capability develops between the first and the third years of their residency training. The power of the methodology using HMM for objective surgical skill assessment arises from the fact that it compiles enormous amount of data regarding different aspects of surgical skill into a very compact model that can be translated into a single number representing the distance from expert performance. Moreover, the methodology is not limited to in-vivo condition as demonstrated in the current study. It can be extended to other modalities such as measuring performance in surgical simulators and robotic systems.

Animals↗

PubMed2000

Nitric acid trihydrate (NAT) in polar stratospheric clouds.

A comprehensive investigation of polar stratospheric clouds was performed on 25 January 2000 with instruments onboard a balloon gondola flown from Kiruna, Sweden. Cloud layers were repeatedly encountered at altitudes between 20 and 24 kilometers over a wide range of atmospheric temperatures (185 to 197 kelvin). Particle composition analysis showed that a large fraction of the cloud layers was composed of nitric acid trihydrate (NAT) particles, containing water and nitric acid at a molar ratio of 3:1; this confirmed that these long-sought solid crystals exist well above ice formation temperatures. The presence of NAT particles enhances the potential for chlorine activation with subsequent ozone destruction in polar regions, particularly in early and late winter.

Journal Article↗

PubMed2000

Pharmaceutical intervention in the JAK/STAT signaling pathway.

Many cytokines exert their effect via the JAK/STAT signal transduction pathway. Due to the medical relevance of many of these cytokines, they are being exploited, either directly, or through antagonists, as therapeutics for a variety of serious diseases. Currently, these therapeutics consist almost entirely of protein products, with all of their attendant drawbacks. Delineation of the signaling mechanisms for the cytokines, however, has allowed the design and implementation of a variety of cell-based and biochemical screens for small molecule mimics or antagonists of these cytokines. Several successful assays will be described along with the advantages of each type of assay. Use of assays of this type should make it possible to discover numerous small molecule cytokine modulators with significant utility in the clinic. Oncogene (2000).

Animals↗

PubMed2000

Sertraline in the treatment of minor depression in nursing home residents: a pilot study.

'Minor' depression affects up to 50% of residents in long-term care facilities and is associated with considerable discomfort, disability and risk of morbidity. Despite the prevalence of this problem, few studies addressing the treatment of these patients have been conducted. In an open clinical trial, 12 nursing home residents who met the DSM-IV description for minor depressive disorder were treated with sertraline for 6 weeks. Adverse effects and clinical response were monitored. All residents tolerated their medication without any significant side-effects. At the completion of the study, the Hamilton Depression Rating Scale and Global Assessment Scale change scores both indicated significant improvement and 75% of the residents met criteria for 'remission'. This preliminary study provides evidence that nursing home residents with minor depression tolerated treatment with sertraline and improved clinically.

Aged↗

PubMed2000

Skills evaluation in minimally invasive surgery using force/torque signatures.

BACKGROUND: One of the more difficult tasks in surgical education is to teach the optimal application of instrument forces and torques necessary to facilitate the conduct of an operation. For laparoscopic surgery, this type of training has traditionally taken place in the operating room, reducing operating room efficiency and potentially affecting the safe conduct of the operation. The objective of the current study was to measure and compare forces and torques (F/T) applied at the tool/hand interface generated during laparoscopic surgery by novice (NS) and experienced (ES) surgeons using an instrumented laparoscopic grasper and to use this data for evaluating the skill level. METHODS: Ten surgeons (five-NS, five-ES) performed a cholecystectomy and Nissen fundoplication in a porcine model. An instrumented laparoscopic grasper with interchangeable standard surgical tips equipped with a three-axis F/T sensor located at the proximal end of the grasper tube was used to measure the F/T at the hand/tool interface. In addition, one axis force sensor located at the grasper's handle was used to measure the grasping force. F/T data synchronized with visual view of the tool operative maneuvers were collected simultaneously via a novel graphic user interface incorporated picture-in-picture video technology. Subsequent frame-by-frame video analysis of the operation allowed a definition of states associated with different tool/tissue interactions within each step of the operation. F/T measured within each state were further analyzed using vector quantization (VQ). The VQ analysis defines characteristic sets of F/T in the database that were defined as F/T signature. RESULTS: The magnitude of F/T applied by NS and ES were significantly different (p < 0.05) and varied based on the task being performed. Higher F/T magnitudes were applied by NS than by ES when performing tissue manipulation, whereas lower F/T magnitudes were applied by NS than by ES during tissue dissection. Furthermore, the time to complete the surgical procedure was longer for NS by a factor of 1.5-4.8 when compared to the time for ES. State analysis suggests that most of this time is consumed in an [idle] state, in which movements of the surgeon make no tissue contact. CONCLUSIONS: Preliminary data suggest that F/T magnitudes associated with the tool/tissue interactions provide an objective means of distinguishing novices from skilled surgeons. Clinical F/T analysis using the proposed technology and methodology may be helpful in training, developing surgical simulators, and measuring technical proficiency during laparoscopic surgery.

Cholecystectomy, Laparoscopic↗