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Biomedical subjects

L Kaplan

Publications and source records attributed to L Kaplan.

At least 37 records · Page 2Linked to original sources

Quality Enhancement Research Initiative in stroke: prevention, treatment, and rehabilitation.

Stroke is the third leading cause of death and a leading cause of adult disability in the United States. Both within and outside of the Veterans Health Administration (VHA), the lack of a systematic approach to stroke prevention and treatment may have contributed to reduced rates of compliance with recommended practices and increased rates of stroke. Gaps in the knowledge base inhibit a systematic approach to high-quality care within the veteran population. Initial recommendations for closing those gaps are proposed. In some cases (eg, systematic anticoagulation management), the VHA is perceived as a leader in applied research; therefore, a systematic national policy for implementing these clinics may significantly reduce stroke rates. In other areas (eg, carotid endarterectomy), databases exist that would help advance quality and outcomes, but short-term studies are necessary to establish their utility. To promote strategic improvement in prevention, treatment, and rehabilitation for veterans who may be at risk or have had a stroke, specific objectives are proposed to (1) identify best practices for the effective delivery of long-term anticoagulation and enhance veterans' access to these services, (2) develop risk-adjusted models for the surgical preventive procedure carotid endarterectomy to understand facility variation in outcomes so practices can be improved, (3) define a systematic acute stroke management system so that high-quality stroke-related care can be generalizable to a variety of VHA settings, and (4) assess the impact of poststroke rehabilitation on risk adjustment and the location of outcomes so as to facilitate the implementation of best rehabilitation practices.

Adult↗

Periodic orbit effects on conductance peak heights in a chaotic quantum dot

We study the effects of short-time classical dynamics on the distribution of Coulomb blockade peak heights in a chaotic quantum dot. The location of one or both leads relative to the short unstable orbits, as well as relative to the symmetry lines, can have large effects on the moments and on the head and tail of the conductance distribution. We study these effects analytically as a function of the stability exponent of the orbits involved, and also numerically using the stadium billiard as a model. The predicted behavior is robust, depending only on the short-time behavior of the many-body quantum system, and consequently insensitive to moderate-sized perturbations and interactions.

Journal Article↗

Short-time effects on eigenstate structure in sinai billiards and related systems

There is much latitude between the requirements of Schnirelman's theorem regarding the ergodicity of individual high-energy eigenstates of classically chaotic systems on the one hand, and the extreme requirements of random matrix theory on the other. It seems likely that some eigenstate statistics and long-time transport behavior bear nonrandom imprints of the underlying classical dynamics while simultaneously obeying Schnirelman's theorem. Indeed this was shown earlier in the case of systems that approach classical ergodicity slowly, and is also realized in the scarring of eigenstates, even in the Planck's over 2pi-->0 limit, along unstable periodic orbits and their manifolds. Here we demonstrate the nonrandom character of eigenstates of Sinai-like systems. We show that mixing between channels in Sinai systems is dramatically deficient compared to random matrix theory predictions. The deficit increases as |ln Planck's over 2pi| for Planck's over 2pi-->0, and is due to the vicinity of the measure zero set of orbits that never collide with the Sinai obstruction. Coarse graining to macroscopic scales recovers the Schnirelman result. Three systems are investigated here: a Sinai-type billiard, a quantum map that possesses the essential properties of the Sinai billiard, and a unitary map corresponding to a quasirandom Hamiltonian. Various wave function and long-time transport statistics are defined, theoretically investigated, and compared to numerical data.

Journal Article↗

Pulse oximetry plethysmographic waveform during changes in blood volume.

Systolic pressure variation (SPV) and its dDown component have been shown to be sensitive factors in estimating intravascular volume in patients undergoing mechanical ventilation. In this study, ventilation-induced changes in pulse oximeter plethysmographic waveform were evaluated after removal and after reinfusion of 10% estimated blood volume. The plethysmographic waveform variation (SPVplet) was measured as the difference between maximal and minimal peaks of waveform during the ventilatory cycle, and expressed as a percentage of the signal amplitude during apnoea. dUp(plet) and dDown(plet) were measured as the distance between the apnoeic plateau and the maximal or minimal plethysmographic systolic waveform, respectively. Intravascular volume was changed by removal of 10% of estimated blood volume and followed by equal volume replacement with Haemaccel. A 10% decrease in blood volume increased SPVplet from mean 17.0 (SD 11.8)% to 31.6 (28.0)% (P = 0.005) and dDown(plet) from 8.7 (5.1)% to 20.5 (12.9)% (P = 0.0005) compared with baseline. Changes in plethysmographic waveform correlated with changes in arterial SPV and dDown (r = 0.85; P = 0.0009). In the absence of invasive arterial pressure monitoring, ventilation-induced waveform variability of the plethysmographic signal measured from pulse oximetry is a useful tool in the detection of mild hypovolaemia.

Adolescent↗

Scar and antiscar quantum effects in open chaotic systems.

We predict and numerically observe strong periodic orbit effects in the properties of weakly open quantum systems with a chaotic classical limit. Antiscars lead to a large number of exponentially narrow isolated resonances when the single-channel (or tunneling) opening is located on a short unstable orbit of the closed system; the probability to remain in the system at long times is thus exponentially enhanced over the random matrix theory prediction. The distribution of resonance widths and the probability to remain are quantitatively given in terms of only the stability matrix of the orbit on which the opening is placed. The long-time remaining probability density is nontrivially distributed over the available phase space; it can be enhanced or suppressed near orbits other than the one on which the lead is located, depending on the periods and classical actions of these other orbits. These effects of the short periodic orbits on quantum decay rates have no classical counterpart, and first appear on times scales much larger than the Heisenberg time of the system. All the predictions are quantitatively compared with numerical data.

Journal Article↗

Measuring scars of periodic orbits.

The phenomenon of periodic orbit scarring of eigenstates of classically chaotic systems is attracting increasing attention. Scarring is one of the most important "corrections" to the ideal random eigenstates suggested by random matrix theory. This paper discusses measures of scars and in so doing also tries to clarify the concepts and effects of eigenfunction scarring. We propose a universal scar measure which takes into account an entire periodic orbit and the linearized dynamics in its vicinity. This measure is tuned to pick out those structures which are induced in quantum eigenstates by unstable periodic orbits and their manifolds. It gives enhanced scarring strength as measured by eigenstate overlaps and inverse participation ratios, especially for longer orbits. We also discuss off-resonance scars which appear naturally on either side of an unstable periodic orbit.

Journal Article↗

Depressive symptoms among spousal caregivers of institutionalized mates with Alzheimer's: boundary ambiguity and mastery as predictors.

The goal of this study was to identify factors that predict whether or not community-dwelling spouses experience depressive symptoms upon institutionalization of a mate with Alzheimer's disease. Eighty-four community-dwelling spouses (50 wives/34 husbands) completed questionnaires. Boundary ambiguity alone accounted for 51% of the variability in the depressive symptoms score, while mastery alone was found to account for 32%. The total explained variance, when controlling for demographic variables, was 68%. In the stepwise regression analysis, it was observed that mastery did not add significantly to the explanation of the depressive symptom score over and above boundary ambiguity. However, boundary ambiguity and mastery were somehow linked together and were powerful in explaining caregiver symptoms of depression. If a goal is to keep caregivers healthy, then interventions and education about how to live with ambiguity and how to be masterful in spite of the ambiguous status of one's mate seem necessary. Clinical implications are discussed. Future research might build upon this study's limitations for an even better understanding of factors that relate to caregiver depressive symptoms.

Adaptation, Psychological↗

Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways.

The AP-2 transcription factors are required for normal growth and morphogenesis during mammalian development. Previous in vitro studies have also indicated that the AP-2 family of proteins may be involved in the etiology of human breast cancer. The AP-2 genes are expressed in many human breast cancer cell lines, and critical AP-2-binding sites are present in both the ERBB-2 (HER2/neu) and estrogen receptor promoters. We have now characterized immunological reagents that enable specific AP-2 family members, including AP-2alpha and AP-2gamma, to be detected in human breast cancer epithelium. Data obtained with these reagents demonstrate that whereas AP-2alpha and AP-2gamma are both present in benign breast epithelia, there is a significant up-regulation of AP-2gamma expression in breast cancer specimens (P = 0.01). There was also a significant correlation between the presence of the AP-2alpha protein and estrogen receptor expression (P = 0.018) and between specimens containing both AP-2alpha/AP-2gamma proteins and ERBB-2 expression (P = 0.003). Furthermore, we detected an association (P = 0.04) between the expression of AP-2gamma and the presence of an additional signal transduction molecule implicated in breast cancer, the insulin-like growth factor I receptor. Analysis of the proximal promoter of the insulin-like growth factor I receptor revealed a novel AP-2-binding site. Thus, AP-2 proteins may directly regulate the transcription of this growth factor receptor. Taken together, these data strongly support a role for the AP-2 gene family in the control of cell growth and differentiation in breast cancer.

Binding Sites↗

Sequential or simultaneous, same-day anterior decompression and posterior stabilization in the management of vertebral osteomyelitis of the lumbar spine.

STUDY DESIGN: A retrospective clinical study of patients with vertebral osteomyelitis of the lumbar spine necessitating surgical treatment. All patients underwent sequential (same-day) or simultaneous anterior decompression and posterior stabilization of the involved vertebrae. OBJECTIVE: To evaluate the efficacy and clinical out-come of sequential or simultaneous anterior and posterior surgical approaches in the management of vertebral osteomyelitis of the lumbar spine. SUMMARY OF BACKGROUND DATA: Anterior approach alone and staged anterior decompression and posterior stabilization have been advocated as the surgical treatment methods of choice for patients with vertebral osteomyelitis of the lumbar spine. The drawbacks of the latter management plan are the necessity to use external support or the delayed patient mobilization and the need for additional anesthesia and surgical trauma. Sequential (same-day) anterior and posterior approaches are used regularly in the surgical management of scoliosis and other spinal deformities. It would appear advantageous to also use the same strategy (i.e., combined same-day double approaches) in the management of vertebral osteomyelitis of the lumbar spine. METHODS: Ten consecutive patients who had a diagnosis of vertebral osteomyelitis of the lumbar spine underwent combined (same-day) anterior and posterior approaches either in a sequential or simultaneous manner. Indications for surgery included neurologic deficit, abscess formation, instability with localized kyphosis formation, and failure of nonoperative treatment. Patients were evaluated clinically and radiographically after surgery. RESULTS: All 10 patients had uneventful surgery. Only one patient required a second surgical procedure because of expulsion of the anterior bone graft and pull-out of instrumentation. All patients were mobilized within the 2 days immediately after surgery. At the mean follow-up examination 30 months after surgery, all patients had regained their motor function and prior ambulatory status. CONCLUSIONS: Patients with lumbar osteomyelitis necessitating surgery can undergo combined, same-day surgery either in a sequential or simultaneous manner. This is a safe and efficient way to control the infection and stabilize the affected segments, allowing for early mobilization of these sick elderly patients.

Aged↗

Hypnotic analgesia: 1. Somatosensory event-related potential changes to noxious stimuli and 2. Transfer learning to reduce chronic low back pain.

Fifteen adults with chronic low back pain (M = 4 years), age 18 to 43 years (M = 29 years), participated. All but one were moderately to highly hypnotizable (M = 7.87; modified 11-point Stanford Hypnotic Susceptibility Scale, Form C [Weitzenhoffer & Hilgard, 1962]), and significantly reduced pain perception following hypnotic analgesia instructions during cold-pressor pain training. In Part 1, somatosensory event-related potential correlates of noxious electrical stimulation were evaluated during attend and hypnotic analgesia (HA) conditions at anterior frontal (Fp1, Fp2), midfrontal (F3, F4), central (C3, C4), and parietal (P3, P4) regions. During HA, hypothesized inhibitory processing was evidenced by enhanced N140 in the anterior frontal region and by a prestimulus positive-ongoing contingent cortical potential at Fp1 only. During HA, decreased spatiotemporal perception was evidenced by reduced amplitudes of P200 (bilateral midfrontal and central, and left parietal) and P300 (right midfrontal and central). HA led to highly significant mean reductions in perceived sensory pain and distress. HA is an active process that requires inhibitory effort, dissociated from conscious awareness, where the anterior frontal cortex participates in a topographically specific inhibitory feedback circuit that cooperates in the allocation of thalamocortical activities. In Part 2, the authors document the development of self-efficacy through the successful transfer by participants of newly learned skills of experimental pain reduction to reduction of their own chronic pain. Over three experimental sessions, participants reported chronic pain reduction, increased psychological well-being, and increased sleep quality. The development of "neurosignatures of pain" can influence subsequent pain experiences (Coderre, Katz, Vaccarino, & Melzack, 1993; Melzack, 1993) and may be expanded in size and easily reactivated (Flor & Birbaumer, 1994; Melzack, 1991, 1993). Therefore, hypnosis and other psychological interventions need to be introduced early as adjuncts in medical treatments for onset pain before the development of chronic pain.

Adult↗

Pregnant women's perspectives on umbilical cord blood banking.

Promising clinical results suggest that umbilical cord blood (UCB) collected after delivery of a child may have many advantages over bone marrow for transplantation. As there are an increasing number of options regarding the collection of UCB, including private and public banking, more pregnant women are likely to be asked to make decisions about UCB collection. We conducted three focus groups with pregnant women to learn about their perspectives on this emerging technology. All the women in these focus groups indicated that they would choose to have UCB collected. Reasons leading to this choice were that the UCB would otherwise be discarded and altruism. Participants indicated that possible reasons to decide not to have UCB collected include concerns about the safety of the mother and neonate, beliefs about the placenta, threats against confidentiality, rejection of UCB, and the influence of fathers. While feeling confident in making an anticipatory decision about UCB collection, women expressed a clear desire to learn much more about the collection, storage (including distinctions between public and private banking), and use of UCB. In addition, they believed that recruitment for UCB collection should occur after sufficient education about UCB and certainly not after delivery and collection. These data will be useful in guiding efforts to help women make decisions about having UCB collected and in developing an appropriate recruitment and informed consent process for donating UCB to a public bank.

Adult↗

Advances and future challenges in non-Hodgkin's lymphoma.

The mortality and morbidity burden of Non-Hodgkin's lymphoma (NHL) is increasing within the human immunodeficiency virus- (HIV-) infected population. Recent improvements in HIV management has meant overall reductions in deaths, especially those due to opportunistic infections, and while the outcome of HIV-related NHL may now be somewhat less grim, the incidence remains high and outcome poor. The median survival of those with HIV-related NHL is only approximately 7 months, although those with high CD4 lymphocyte counts seem to do somewhat better. Improved management of the underlying HIV infection, more effective infusional chemotherapy regimens, moderately effective second line regimens, and new investigational approaches all offer promising hope that improvements will soon be seen for the treatment of HIV-related systemic NHL. Immunotherapy, monoclonal antibodies, and adoptive immunotherapy targeting Epstein Barr virus (EBV) all represent novel experimental treatment approaches that are becoming possible based on our increased understanding of the pathogenesis of HIV-related lymphoma. Primary central nervous system lymphoma (PCNSL) in HIV patients has declined in incidence and there now is a rapid, less invasive diagnostic test. The presence of EBV DNA in the cerebral spinal fluid of HIV patients with focal brain lesions strongly suggests a diagnosis of PCNSL. Unfortunately, this disease remains difficult to treat in such an immunocompromised patient population. Further work is needed in order to prevent and effectively manage these diseases.

Drug Therapy↗

Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation.

The insulin-like growth factor-I receptor (IGF-IR) plays a critical role in cell growth regulation and transformation. The radiosensitivity of NIH 3T3 fibroblasts overexpressing either wild-type or mutant IGF-IR was examined. High levels of wild-type IGF-IR conferred radioresistance, and mutational analysis revealed that this effect correlated with the transforming capacity but not the mitogenic activity of the receptor. The radioresistant phenotype was reversed when the cells were incubated with antisense oligonucleotides targeted to IGF-IR mRNA, demonstrating that IGF-IR directly influences radioresistance. The clinical significance of these findings was examined in an immunohistochemical analysis of primary breast tumors, revealing that high levels of IGF-IR in tumor samples were highly correlated with ipsilateral breast tumor recurrence (IBTR) following lumpectomy and radiation therapy (P = 0.001). Subgroup analysis revealed that, for early breast tumor relapses (within 4 years of initial breast tumor diagnosis), elevated levels of IGF-IR were strongly associated with IBTR (P = 0.004) but IGF-IR expression was not prognostic for IBTR from breast cancer patients with late relapses (P was not significant). These studies provide evidence for the influence of IGF-IR on cellular radioresistance and response to therapy and raise the possibility that the radiocurability of selected tumors may be improved by pharmaceutical strategies directed toward the IGF-IR.

3T3 Cells↗

Aspects of spinal deformity in familial dysautonomia (Riley-Day syndrome).

Familial dysautonomia (FD) is a rare autosomal recessive disease occurring in Jews of Ashkenazi descent, with only some 500 recognized cases. The causative gene was identified on chromosome 9. FD is of considerable orthopedic interest, because of the prevalence of skeletal deformity. About 90% of surviving dysautonomic children will develop a spinal curvature, commonly a scoliosis. The scoliotic curve is usually kyphotic rather than lordotic, and appears during the first decade of life. Fifty-one of the 90 reported cases of familial dysautonomia in Israel involved patients who were seen at the scoliosis clinic for assessment and treatment of their spinal deformities. Most of the patients presented with a scoliotic deformity associated in 37 cases with an increased thoracic kyphosis. In our series orthotic treatment and physiotherapy were found to be minimally successful at best. Surgical treatment of the spine was performed in 13 of 51 patients in this series. A retrospective review of these patients' charts and radiographs was carried out. Six years of follow-up are reported. The primary indication for surgery was progression of the spinal curve. Only posterior spinal fusions were performed. Anterior transthoracic procedures were avoided in spite of the significance of the kyphotic deformity, because of the frequency of pulmonary complications. Harrington distraction and compression instrumentation was used. Three-millimeter compression rods were used in a distraction mode in thin, young children. "Harri-Luque" segmental sublaminar wiring technique and Wisconsin spinous process segmental wiring was used in some. In all cases, the spine fusion was supplemented by bank bone only, to avoid the additional trauma of graft removal. We believe that surgical intervention is advantageous, if done early in the evolution of spinal deformity. Greater technical difficulties and a higher complication rate were encountered in this series relative to the problems usually seen after spinal deformity surgery in children; this is all the more important in a disease in which general anesthesia is an additional major complicating factor. It is hoped that the improved physical condition now seen after early gastrostomy and fundoplication will aid in reducing this high complication rate. Only a small degree (about 25%) of correction was achieved in the majority of patients. Some of this apparent rigidity derived from the inability to apply sufficient instrumental corrective force because of the friable osteoporotic bone. After surgery, there was a marked decrease in the frequency of pneumonia and an improvement in the degree of ataxia, for reasons not understood, which led to an obvious improvement in the quality of life.

Adolescent↗