Biomedical subjects
J Katz
Publications and source records attributed to J Katz.
Several levels of EGF receptor signaling during photoreceptor specification in wild-type, Ellipse, and null mutant Drosophila.
Dominant Ellipse mutant alleles of the Drosophila EGF receptor homologue (DER) dramatically suppress ommatidium development in the eye and induce ectopic vein development in the wing. Their phenotype suggests a possible role for DER in specifying the founder R8 photoreceptor cells for each ommatidium. Here we analyze the basis of Ellipse mutations and use them to probe the role of DER in eye development. We show that Elp mutations result from a single amino acid substitution in the kinase domain which activates tyrosine kinase activity and MAP kinase activation in tissue culture cells. Transformant studies confirmed that the mutation is hypermorphic in vivo, but the DER function was elevated less than by ectopic expression of the ligand spitz. Ectopic spi promoted photoreceptor differentiation, even in the absence of R8 cells. Pathways downstream of DER activation were assessed to explore the basis of these distinct outcomes. Elp mutations caused overexpression of the Notch target gene E(spl) mdelta and required function of Notch to suppress ommatidium formation. The Elp phenotype also depended on the secreted protein argos and was reverted in Elp aos double mutants. Complete loss of DER function in clones of null mutant cells led to delay in R8 specification and subsequently to loss of mutant cells. The DER null phenotype was distinct from that of either spitz or vein mutants, suggesting that a combination of these or other ligands was required for aspects of DER function. In normal development DER protein was expressed in most retinal cells, but at distinct levels. We used an antibody specific for diphospho-ERK as well as expression of the DER target gene argos to assess the pattern of DER activity, finding highest activity in the intermediate groups of cells in the morphogenetic furrow. However, studies of mutant genotypes suggested that this activity may not be required for normal ommatidium development. Since we saw distinct phenotypic effects of four different levels of DER activity associated with wild-type, null mutant, Elp mutant, or fully activated DER function, we propose that multiple thresholds separate several aspects of DER function. These include activation of N signaling to repress R8 specification, turning on argos expression, and recruiting photoreceptors R1-R7. It is possible that during normal eye development these thresholds are attained by different cells, contributing to the pattern of retinal differentiation.
Methodological variations in estimating apparent progressive visual field loss in clinical trials of glaucoma treatment.
OBJECTIVES: To compare methods to estimate the incidence of visual field progression used by 3 large randomized trials of glaucoma treatment by applying these methods to a common data set of annually obtained visual field measurements of patients with glaucoma followed up for an average of 6 years. METHODS: The methods used by the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), and the Early Manifest Glaucoma Treatment study (EMGT) were applied to 67 eyes of 56 patients with glaucoma enrolled in a 10-year natural history study of glaucoma using Program 30-2 of the Humphrey Field Analyzer (Humphrey Instruments, San Leandro, Calif). The incidence of apparent visual field progression was estimated for each method. Extent of agreement between the methods was calculated, and time to apparent progression was compared. RESULTS: The proportion of patients progressing was 11%, 22%, and 23% with AGIS, CIGTS, and EMGT methods, respectively. Clinical assessment identified 23% of patients who progressed, but only half of these were also identified by CIGTS or EMGT methods. The CIGTS and the EMGT had comparable incidence rates, but only half of those identified by 1 method were also identified by the other. CONCLUSIONS: The EMGT and CIGTS methods produced rates of apparent progression that were twice those of the AGIS method. Although EMGT, CIGTS, and clinical assessment rates were comparable, they did not identify the same patients as having had field progression.
Use of cuffed oropharyngeal vs laryngeal mask airway in elderly patients.
PURPOSE: This study was designed to compare the new cuffed oropharyngeal airway (COPA) to the laryngeal mask airway (LMA) in elderly patients. METHODS: In a randomized, controlled study, 80 patients, age > or = 65, ASA I-III, undergoing urology procedures, were managed with either COPA or LMA. Propofol requirements for insertion of the devices, ease of insertion and removal, airway manipulations, mean arterial pressure, heart rate, P(ET)CO2, SpO2, peak inspiratory pressure, selection of the appropriate size of the device and leaks, fibreoptic visualization of larynx and complications were studied. RESULTS: There were more airway manipulations in the COPA group than in the LMA group (40% and 5% respectively) whereas P(ET)CO2 was higher in the LMA group (P < 0.05). In 60% of COPA patients the vocal cords could not be visualized but ventilation was adequate in all but two cases. Postoperative sore throat occurred in 20% of patients with LMA vs 10% with COPA). Bloody secretions on the device were present in two patients managed with LMA. CONCLUSION: In elderly patients COPA required more airway manipulations than the LMA. Laryngeal mask airway caused more sore throats, but was better for fibreoptic visualisation of the larynx. Both are excellent options when intubation is not indicated/desired.
Urinary diversion after total pelvic exenteration for rectal cancer.
BACKGROUND: Total cystectomy is indicated for the treatment of bulky primary rectal cancers as well as previously treated, locally recurrent tumors that invade the bladder, prostate, seminal vesicle, or urethra. We review a 10-year Memorial Sloan-Kettering Cancer Center experience with urinary diversion in this setting. METHODS: Between April 1988 and June 1998, 47 patients underwent urinary diversion during a total pelvic exenteration for rectal cancer. Charts and operative records were reviewed to determine pathological findings, short-term and long-term urological complications, and survival. RESULTS: Forty-seven patients (25 males and 22 females; median age, 62 years; age range, 27-79 years) were included. Sixteen (34%) patients underwent cystectomy for a primary rectal tumor (including 1 for rectal sarcoma and 1 for synchronous invasive bladder cancer), and 31 (66%) patients underwent surgery for a locally recurrent rectal cancer. Thirty (64%) patients underwent preoperative, 18 (38%) underwent intraoperative, and 11 (23%) underwent postoperative radiotherapy. Twenty-six (55%) patients received preoperative and 16 (34%) underwent postoperative chemotherapy. Two patients had continent ileal cecal reservoirs, 1 a colonic conduit, and the remaining 45 had ileal conduits. The tumor invaded the bladder in 24 (51%) patients, the prostate in 5 (11%) patients, and the seminal vesicle in 5 (11%) patients. Complete resection was achieved in 42 (89%) patients. There were a total of eight complications in eight (17%) patients. There were three early complications, two of which were ileoureteral anastomotic leaks, one managed by reoperation, the second by percutaneous drainage, and one moderate hydronephrosis managed expectantly. There were five late complications; three patients had ureteral stricture/stenosis, leading to nephrectomy in one patient and percutaneous stenting in two patients. Two patients developed late hydronephrosis, so far managed expectantly. There was one perioperative death. After a median follow-up of 16.83 months, 20 patients were dead of the disease, 6 were alive with disease recurrence, 2 were dead of other causes, and 19 had no evidence of disease. Three-year actuarial disease-specific survival was 34%. CONCLUSIONS: Complete resection of bulky primary or locally recurrent rectal cancer can be performed with acceptable urological morbidity. Complete resection was obtained in 89% of patients, with 72% having urological organ invasion. Overall urological complications of 17% are acceptably low despite intensive perioperative radiation and chemotherapy. Disease-specific survival in these patients remains limited.
Measurement of pain.
Pain is a personal, subjective experience influenced by cultural learning, the meaning of the situation, attention, and other psychologic variables. Approaches to the measurement of pain include verbal and numeric self-rating scales, behavioral observation scales, and physiologic responses. The complex nature of the experience of pain suggests that measurements from these domains may not always show high concordance. Because pain is subjective, patients' self-reports provide the most valid measure of the experience. The VAS and the MPQ are probably the most frequently used self-rating instruments for the measurement of pain in clinical and research settings. The MPQ is designed to assess the multidimensional nature of pain experience and has been demonstrated to be a reliable, valid, and consistent measurement tool. A short-form MPQ is available for use in specific research settings when the time to obtain information from patients is limited and when more information than simply the intensity of pain is desired. The DDS was developed using sophisticated psychophysical techniques and was designed to measure separately the sensory and unpleasantness dimensions of pain. It has been shown to be a valid and reliable measurement of pain with ratio-scaling properties and has recently been used in a clinical setting. Behavioral approaches to the measurement of pain also provide valuable data. Further development and refinement of pain measurement techniques will lead to increasingly accurate tools with greater predictive powers.
Scoring systems for measuring progression of visual field loss in clinical trials of glaucoma treatment.
OBJECTIVES: To compare the statistical properties of two visual field scoring systems used by clinical trials of glaucoma treatments with a view to their performance as longitudinal measures of visual field progression. DESIGN: Cohort study comparing the scoring systems used by the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS) using pairs of visual fields (C-30-2 of the Humphrey Analyzer) spaced 1 year apart. PARTICIPANTS: Sixty-seven eyes of 56 subjects with glaucomatous visual field loss from a natural history study of glaucoma were examined. METHODS: Because both scoring systems are scaled so that they range from 0 to 20, the AGIS and CIGTS scores were compared by scatterplot, Pearson correlation, and the mean difference between scores. The difference between pairs of scores 1 year apart was used to compare the temporal variability of each scoring system. The proportion of subjects whose visual field "deteriorated" in 1 year by the amount specified for unconfirmed progression in each clinical trial was calculated. MAIN OUTCOME MEASURES: Mean difference in scores 1 year apart and the variance of these differences were measured. RESULTS: The median scores for the first of the two fields was 5.2 (interquartile range [IQR] = 9.8) for CIGTS and 5.0 (IQR = 7.0) for AGIS. The CIGTS scores were slightly larger than AGIS scores by an average of 0.5 (P = 0.06). The mean CIGTS score of the baseline fields was 0.06 (standard deviation = 3.8) higher than the mean of the second fields and 0.12 (standard deviation = 2.8) higher for AGIS. Fifteen percent of eyes had CIGTS scores that deteriorated by three or more (the cutoff for unconfirmed progression) over 1 year, while 7.5% of eyes had AGIS scores that deteriorated by four or more (the AGIS cutoff for unconfirmed progression) over the same period. Twenty-one percent improved by CIGTS criteria, while 12% improved by AGIS criteria. CONCLUSIONS: CIGTS scores are systematically slightly higher than AGIS scores. The CIGTS scoring system has higher temporal variability than the AGIS system. The CIGTS criterion for unconfirmed progression over a 1-year period is likely to lead to higher estimated rates of progression than the AGIS criteria. This is mostly because of the difference in the definition of progression between the two study criteria.
Racial differences in the prevalence of age-related macular degeneration: the Baltimore Eye Survey.
OBJECTIVE: To determine the prevalence of age-related macular degeneration (AMD) and signs of age-related maculopathy in a population-based sample of blacks and whites 40 years of age or older from East Baltimore. DESIGN: Cross-sectional population-based study. PARTICIPANTS: A total of 5308 black and white subjects received a screening eye examination that included fundus photography. MAIN OUTCOME MEASURES: Stereoscopic color fundus photographs were graded for the presence and severity of drusen, pigmentary abnormalities, geographic atrophy, and choroidal neovascularization in the macula. RESULTS: Drusen > or = 64 microm were identified in about 20% of individuals in both groups, but large drusen (>125 microm) were more common among older whites (15% for whites versus 9% for blacks over 70). Pigmentary abnormalities were also more common among older whites (7.9% for whites versus 0.4% for blacks over 70). Age-related macular degeneration was more prevalent among whites than blacks. The prevalence of AMD was 2.1 % among whites over 70 years of age. No cases of AMD were detected among 243 black subjects in this age group. Logistic regression adjusting for age, sex and smoking (current, former, or never) detected an odds ratio of 4.4 (95% confidence interval: 1.5-12.4) for whites with AMD compared with blacks. CONCLUSION: Although drusen are common in both blacks and whites over the age of 40, more severe forms of age-related maculopathy and late AMD are more prevalent in older whites.
The patient's motivation in seeking complementary therapies.
The motivations of cancer patients in seeking complementary therapies are, fundamentally, self-healing motivations which, when engaged appropriately, can contribute to the patient's psychological and physical well being. In this paper, we apply a theoretical model, the Risk Adaptation Model, to furthering the clinical understanding of the motivations of cancer patients in seeking complementary therapies. The model identifies six discrete cognitive processes which, in combination, are hypothesized to play a central role in therapy seeking. Emphasis in this model is placed on the patient's need to maintain positive expectancies (optimism) when faced with the risk and uncertainty of cancer. This understanding of complementary-therapy seeking is grounded in the perspective that clinicians must respect the autonomy of cancer patients in their quest for appropriate therapies, and assist rather than direct their process of therapy-seeking.
Pain and tension are reduced among hospital nurses after on-site massage treatments: a pilot study.
Tension and pain are common occupational hazards of modern-day nursing, especially given recent changes to the health care system. The aims of the pilot study were (1) to evaluate the feasibility of carrying out a series of eight 15-minute workplace-based massage treatments, and (2) to determine whether massage therapy reduced pain and stress experienced by nursing staff at a large teaching hospital. Twelve hospital staff (10 registered nurses and 2 nonmedical ward staff) working in a large tertiary care center volunteered to participate. Participants received up to eight, workplace-based, 15-minute Swedish massage treatments provided by registered massage therapists. Pain, tension, relaxation, and the Profile of Mood States were measured before and after each massage session. Pain intensity and tension levels were significantly lower after massage (P < .01). In addition, relaxation levels and overall mood state improved significantly after treatments (P < .01). The results of this pilot study support the feasibility of an eight-session, workplace-based, massage therapy program for pain and tension experienced by nurses working in a large teaching hospital. Further research is warranted to study the efficacy of workplace massage in reducing stress and improving overall mood.
Sexual desire discrepancies: effects on sexual and relationship satisfaction in heterosexual dating couples.
Sexual desire discrepancies and the associations between desire discrepancies and relationship adjustment (i.e., sexual and relationship satisfaction) in heterosexual dating couples (N = 72) were examined Desire discrepancies were assessed via two methods: (1) a couple-based index created using both individuals' reports of sexual desire and (2) an individual-based index using each person's own subjective perception of a desire discrepancy within the couple. Both indices were associated with women's adjustment, whereas only individual perceptions of discrepancies were associated with men's adjustment. The association between desire discrepancies and general relationship satisfaction was fully mediated by level of sexual satisfaction for both men and women. Women whose sexual desire level was lower than their partners' endorsed lower levels of relationship adjustment relative to women whose desire was either greater than or similar to their partners'. Implications for the assessment of sexual desire differences in couples are discussed.
Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study.
This study was designed to test the hypothesis that high-dose asparaginase consolidation therapy improves survival in pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five hundred and fifty-two patients (357 patients with T cell acute lymphoblastic leukemia (ALL) and 195 patients with advanced stage lymphoblastic lymphoma) were enrolled in POG study 8704 (T-3). Treatment included rotating combinations of high-dose myelosuppressive chemotherapy agents proven to be effective in T cell ALL in other POG group-wide or local institutional protocols (including vincristine, doxorubicin, cyclophosphamide, prednisone, asparaginase, teniposide, cytarabine and mercaptopurine). After achieving a complete remission (CR), patients were randomized to receive or not receive high-dose intensive asparaginase consolidation (25,000 IU/m2) given weekly for 20 weeks by intramuscular injection. Intrathecal chemotherapy (methotrexate, hydrocortisone and cytarabine) was given to prevent CNS disease, and CNS irradiation was used only for patients with leukemia and an initial WBC of >50,000/microl or patients with active CNS disease at diagnosis. CR was achieved in 96% of patients. The high-dose asparaginase regimen was significantly superior to the control regimen for both the leukemia and lymphoma subgroups. Four-year continuous complete remission rate (CCR) for the leukemia patients was 68% (s.e. 4%) with asparaginase as compared to 55% (s.e. 4%) without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%) with asparaginase and 64% (s.e. 6%) in the controls. The overall one-sided logrank test had a P value <0.001 favoring asparaginase, while corresponding values were P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities were tolerable, but there were 18 failures due to secondary malignancies (16 with non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (leukemia patients) nor lymphoma stage were major prognostic factors. We conclude that when added to a backbone of effective rotating agents, repeated doses of asparaginase during early treatment improve the outcome for patients with T cell leukemia and advanced stage lymphoblastic lymphoma.
Tumor necrosis factor alpha and interferon gamma--induced cell growth arrest is mediated via insulin-like growth factor binding protein-3.
Retinoic acid (RA), and the combination of TNFalpha and Interferon (IFN-gamma) inhibit human salivary gland tumor (HSG) cell growth with the combination of all three being even more inhibitory (P<0. 05). Previous studies have demonstrated that these inhibitory effects of RA, and the combination of TNFalpha and IFN-gamma are associated with increased accumulation of IGFBP-3 in the culture medium of HSG cells. Therefore, we set out to determine if the increase in IGFBP-3 was due to increased production of IGFBP-3 by the cells and whether IGFBP-3 played a causative role in the inhibition of cellular proliferation. TNFalpha and IFN-gamma induced a rise in IGFBP-3 mRNA levels between 4 and 8 h, which returned to control levels after 24 h. IGFBP-3 was shown to inhibit HSG cell growth at concentrations of >/=75 U (P<0.05). When antibodies to IGFBP-3 were used with TNFalpha and IFN-gamma, the inhibitory effect of the cytokines on cell growth was diminished. Retinoic acid with TNFalpha and IFN-gamma had a marked inhibitory effect (P<0.05) which was similarly reversed by increasing concentrations of IGFBP-3 antibody. The present data support the hypothesis that the combination of TNFalpha and IFN-gamma with retinoic acid exert their anti-proliferative effect on HSG cells by reducing the mitogenic effect of IGF-I due to a shift in IGF-I from the free to the IGFBP-3-bound form.
Estimating the magnitude of close-up work in school-age children: a comparison of questionnaire and diary instruments.
BACKGROUND: Numerous scientists have noted a relationship between close-up work and myopia. METHODS: A questionnaire and four 24-hour diaries were developed to estimate close-up work activity in a cohort study of close-up work and myopia progression in Singapore children. The number of hours per day that children engaged in each type of close-up work activity over a weekday and weekend during the school term, during the examination period, and in the vacation were estimated. RESULTS: The children spent an average of 6.6 hours per day on total weighted average close-up work, of which 4.3 hours were spent on reading and writing. The intra-class correlation coefficient for the reproducibility of the questionnaire was 0.87 (95% CI 0.85-0.91). The intra-class correlation coefficient for total weighted close-up work was 0.50 (95% CI 0.34-0.66) when the questionnaire was compared with the four 24-hour diaries. The amount of close-up work activity increased with age. CONCLUSIONS: A questionnaire for close-up work was developed and proven to be reproducible and comparable to four 24-hour diaries.
Learning disabilities: compromising undergraduate GPAs.
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Distance, lighting, and parental beliefs: understanding near work in epidemiologic studies of myopia.
PURPOSE: To develop measures and indices of factors (distance of eye from object, posture, and lighting) that may modify a possible effect of near work activity on myopia. METHODS: The duration of near work, the distance of an object from eye, lighting conditions, and other sociodemographic characteristics were asked in an interview. Both distance and lighting information from the questionnaire were compared with more precise measurements. RESULTS: Diopter hours were quantified as the duration of near work multiplied by the reciprocal of the distance which the activity was performed. The intraclass correlation coefficient of the reliability of distance information for each type of near work activity ranged from 0.43 to 0.91. Home light meter readings were significantly higher for children who were reading under both room and reading light, and the distances from the questionnaire were comparable to the measured distances. CONCLUSIONS: Measures of posture, distance, and lighting factors have been developed to study the possible effect modifiers of the effects of near work on myopia.
Mechanisms of extraocular muscle injury in orbital fractures.
The gross and microscopic events that occur after orbital blowout fractures were evaluated to assess the mechanisms of diplopia and muscle injury. Intramuscular and intraorbital pressures were evaluated in experimental animals, in cadavers, and at the time of orbital fracture explorations for repair of orbital fractures in humans. Histologic and circulatory changes, muscle pressure recordings, and operative observations were evaluated. Creation of a compartment syndrome was evaluated to include a histologic evaluation of the orbital fibrous sheath network for the extraocular muscles and the intramuscular vasculature. These experiments and observations do not support the role of a compartment syndrome in ocular motility disturbances because (1) intramuscular pressures were subcritical in both humans and animals; (2) no limiting fascial compartment could be demonstrated; and (3) microangiograms and histologic evaluations did not confirm areas of compartmental ischemic necrosis. Muscle contusion, scarring within and around the orbital fibrous sheath network, nerve contusion, and incarceration within fractures remain the probable causes of diplopia, with the most likely explanations being muscle contusion and fibrosis or incarceration involving the muscular fascial network.
Unusual peripheral odontogenic tumors in the differential diagnosis of gingival swellings.
Differential diagnosis of gingival mass lesions includes several conditions and causes. Peripheral odontogenic tumors may mimic gingival swellings and, although rare, must be included in the differential diagnosis. The purpose of this article is to describe 3 different cases of peripheral odontogenic tumors and to discuss the differential diagnosis of gingival swelling. Histologic examination is mandatory when localized gingival swellings are surgically removed.