Biomedical subjects
J Gottlieb
Publications and source records attributed to J Gottlieb.
[Surveillance of invasive mold infections in lung transplant recipients: effect of antimycotic prophylaxis with itraconazole and voriconazole].
Between January 2002 and December 2003 all 157 patients (pts) that underwent lung transplantation (LTx) at our institution were prospectively screened for invasive aspergillosis (IA) during their perioperative hospital stay. Patients were regarded as IA positive, if they met the EORTC criteria for 'probable' or 'proven' IA. Records of pts were screened retrospectively for antimycotic prophylaxis. Eight of the 157 pts developed 'probable' or 'proven' IA (5.1%) within 17 +/- 10 days after LTx. This was associated with a 14-fold increased mortality compared with all pts without aspergillosis (P < 0.01, OR 13.8, CI(95%) 2.5-82). Preoperative colonization with Aspergillus was a significant risk factor for IA (P < 0.001, OR 21.9, CI(95%) 4.9-97). We switched our prophylactic strategies to the primary administration of voriconazole in high risk pts (pre-LTx colonization) starting in December 2002. Six pts (6%) of 101 pts receiving itraconazole for antimycotic prophylaxis beginning at postoperative day (POD) one developed IA, of which three pts showed cerebral aspergillosis. One pt (5%) of 18 pts receiving voriconazole prophylaxis developed IA, while 10 pts showed pretransplant colonization with Aspergillus species. Thirty-eight pts received itraconazole prophylaxis at a later time point (>POD 14). By switching our prophylactic strategy to the use of voriconazole in high risk pts, we have decreased the incidence of IA from 8% (six of 75) in 2002 to 2% (two of 82) in 2003. This study shows a high incidence of IA during the very early postoperative course after LTx of 5%. This is associated with a significantly increased risk for mortality. Voriconazole prophylaxis appears to be superior to itraconazole, especially in high risk pts with pretransplant Aspergillus colonization.
[Lung transplantation. Possibilities and limitations].
Lung transplantation is an option for patients with endstage pulmonary diseases without contraindications. Recent European studies showed a survival benefit for patients with cystic fibrosis, fibrosis and emphysema after lung transplantation. Early mortality has been reduced recently by surgical improvements. Life expectancy after lung transplantation has improved in recent years but is still lower than in patients with other solid organ transplantations. Quality of life is consistently improved but exercise tolerance keeps reduced in comparison to the normal population. Specific problems described in detail are frequent organ rejections and infections, airway problems and a high incidence of malignant diseases. 5-year survival after lung transplantation is in average 60%.
Understanding the value of diabetic retinopathy screening.
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The lateral intraparietal area as a salience map: the representation of abrupt onset, stimulus motion, and task relevance.
Neurons in the lateral intraparietal area (LIP) of the monkey represent salient stimuli. They respond to recently flashed stimuli that enter their receptive fields by virtue of saccades better than they respond to stable, behaviorally irrelevant stimuli brought into their receptive fields by saccades. They respond transiently to abrupt motion onsets, but have no directional selectivity. They respond to stable stimuli that are the targets for saccadic eye movements, but far less before the same saccades without stimuli. LIP is important in the attentional mechanisms preceding the choice of saccade target rather than in the intention to generate the saccade itself.
The effect of perceived duration of physical disability on attitudes of school children toward friendship and helping.
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[Causative treatment after surgical treatment of varicose veins in Denmark].
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Activity of neurons in the lateral intraparietal area of the monkey during an antisaccade task.
The close relationship between saccadic eye movements and vision complicates the identification of neural responses associated with each function. Visual and saccade-related responses are especially closely intertwined in a subdivision of posterior parietal cortex, the lateral parietal area (LIP). We analyzed LIP neurons using an antisaccade task in which monkeys made saccades away from a salient visual cue. The vast majority of neurons reliably signaled the location of the visual cue. In contrast, most neurons had only weak, if any, saccade-related activity independent of visual stimulation. Thus, whereas the great majority of LIP neurons reliably encoded cue location, only a small minority encoded the direction of the upcoming saccade.
Biochemical analyses of mutations in the HSV-1 helicase-primase that alter ATP hydrolysis, DNA unwinding, and coupling between hydrolysis and unwinding.
Herpes simplex virus type 1 encodes a heterotrimeric helicase-primase composed of the products of the UL5, UL52, and UL8 genes. UL5 possesses six motifs conserved among superfamily 1 of helicase proteins. Substitutions of conserved residues in each motif abolishes DNA replication in vivo (Zhu, L., and Weller, S. K. (1992) J. Virol. 66, 469-479). Purified UL5.52 harboring a Gly to Ala change in motif V retains primase and helicase activities in vitro but exhibits a higher KM for single-stranded DNA and lower DNA-dependent ATPase activity (Graves-Woodward, K. L., and Weller, S. K. (1996) J. Biol. Chem. 272, 13629-13635). We have purified and characterized six other subcomplexes with residue changes in the UL5 helicase motifs. Each variant subcomplex displays at least wild type or greater levels of primase and DNA binding activities, but all are defective in helicase activity. Mutations in motifs I and II exhibit profound decreases in DNA-dependent ATPase activity. Mutations in motifs III-VI decrease DNA-dependent ATPase activity 3-6-fold. Since mutations in motifs III, IV, V, and VI do not eliminate ATP hydrolysis or DNA binding, we propose that they may be involved in the coupling of these two activities to the process of DNA unwinding. This analysis represents the first comprehensive structure-function analysis of the conserved motifs in helicase superfamily 1.
Students' gender and examination of patients in a third-year family medicine clerkship.
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The perception of risk over time as a factor influencing attitudes toward children with physical disabilities.
The impact of perception of risk (a perception of possible psychological harm) on attitudes toward friendship with and offering help to children with physical disabilities was examined, and the stability of the perception in specific contexts, over time, was investigated. Participants were 510 children without physical disabilities between the ages of 8 and 19 years who were assigned to 1 of 12 experimental conditions in a basic 2 x 2 x 3 (Involvement x Interview x Grade) design. Results indicated significantly more favorable attitudes on helping than on friendship. Over time, attitudes toward friendship became more positive, whereas attitudes toward helping became somewhat more negative, but these effects interacted with the age of the participant and the degree of perceived risk.
Should half of all medical school graduates enter primary care? Perceptions of faculty members at Jefferson Medical College.
PURPOSE: This study was undertaken to promote communication among faculty regarding the impact of a proposed goal that 50% of the graduates of Jefferson Medical College enter generalist careers. Since the opinions and attitudes of faculty regarding career decisions may directly or indirectly influence students, the authors investigated faculty's views of the optimal ratio of primary care to non-primary care physicians in the workforce and their perceptions of the effect on medical education, research, and health care delivery if the 50% goal were to be mandated. METHOD: A questionnaire was mailed in January 1994 to all 684 salaried faculty of Jefferson Medical College. Respondents' opinions about the optimal primary care to non-primary care ratio and their perceptions of the effects of implementing the 50% goal on 21 areas related to medical education, research, and health care delivery were examined using a Likert-type scale. Obstacles perceived by non-primary care physicians as preventing their practice of primary care were also among the outcome measures. RESULTS: A total of 275 completed questionnaires were received (40% response rate; 72 primary care physicians, 141 non-primary care physicians, and 62 non-physicians). The median and mode of an optimal primary care to non-primary care ratio were both 50/50. Faculty, in general, perceived that implementing the 50% goal would enhance public access to primary care, physician-patient relationships, utilization of non-physicians, and the career satisfaction of generalists. They predicted decreases in costs of care, freedom of career choice, funding, and interest in research. The primary care physicians perceived greater enhancements of the image of physicians, quality of care, and satisfaction of generalists and subspecialists than did the non-primary care physicians. Gender and age did not affect the perceptions. A lack of appropriate training was identified by 45% and a lack of interest by 28% of the non-primary care physicians as major obstacles to their practice of primary care medicine. CONCLUSION: The faculty members' positive and negative views of the proposed reform can provide useful information to the institution in understanding the potential impediments to increasing the numbers of generalist graduates. The generalists had significantly different views from the subspecialists about the impact of increasing the proportion of primary care physicians on health care delivery and research. In general the primary care physicians were more likely to view the proposed changes as beneficial than were the non-primary care physicians.
Interaction of herpes simplex virus type 1 DNA polymerase and the UL42 accessory protein with a model primer template.
Genetic and biochemical studies have shown that the products of the herpes simplex virus type 1 (HSV-1) DNA polymerase (UL30) and UL42 genes are both required for viral DNA replication. A number of studies have previously suggested that these two proteins specifically interact, and more recent studies have confirmed that the viral DNA polymerase from HSV-1-infected cells consists of a heterodimer of the UL30 (Pol; the catalytic subunit) and UL42 polypeptides. A comparison of the catalytic properties of the Pol-UL42 complex with those of the isolated subunits of the enzyme purified from recombinant baculovirus-infected insect cells indicated that the Pol-UL42 complex is more highly processive than Pol alone on singly primed M13 single-stranded substrates. The results of these studies are consistent with the idea that the UL42 polypeptide is an accessory subunit of the HSV-1 DNA polymerase that acts to increase the processivity of polymerization. Preliminary experiments suggested that the increase in processivity was accompanied by an increase in the affinity of the polymerase for the ends of linear duplex DNA. We have further characterized the effect of the UL42 polypeptide on a defined hairpin primer template substrate. Gel shift and filter binding studies show that the affinity of the Pol catalytic subunit for the 3' terminus of the primer template increases 10-fold in the presence of UL42. DNase I footprinting experiments indicate that the Pol catalytic subunit binds to the primer template at a position that protects 14 bp of the 3' duplex region and an adjacent 18 bases of the single-stranded template. The presence of the UL42 polypeptide results in the additional protection of a contiguous 5 to 14 bp in the duplex region but does not affect the 5' position of the Pol subunit. Free UL42 protects the entire duplex region of the substrate but does not bind to the single-stranded region. Taken together, these results suggest that the increase in processivity in the presence of UL42 is related to the double-stranded DNA-binding activity of free UL42 and that the role of UL42 in the DNA polymerase complex is to act as a clamp, decreasing the probability that the polymerase will dissociate from the template after each cycle of catalysis.
US-assisted bronchoscopy with use of miniature transducer-containing catheters.
PURPOSE: To demonstrate the value of ultrasound (US) guidance during flexible bronchoscopic procedures in a series of patients with known or suspected pulmonary neoplasms. MATERIALS AND METHODS: US-guided bronchoscopy was carried out as an adjunct to conventional bronchoscopy for the diagnosis of mediastinal, hilar, or parenchymal neoplasms in 25 patients with masses previously detected with chest radiography or computed tomography. Miniature transducer-containing catheters were inserted through the biopsy port of the flexible bronchoscope, and cross-sectional real-time US scans of tumors, lymph nodes, and blood vessels were obtained. RESULTS: Among six cases of peripheral masses and 19 cases of central masses, additional information was provided in 18 cases (72%). This information was used to choose the optimal site for transmural biopsy. CONCLUSION: These preliminary results suggest that this US procedure may become an important diagnostic tool during bronchoscopy, due to the ability to identify structures beyond the lumen of the tracheobronchial tree.
[Significant prognostic factors for recurrence-free survival after surgical treatment of head-neck melanoma].
The clinico-pathological and therapeutic data of 512 patients with clinical stage I invasive head and neck melanoma of the skin were re-evaluated. There were 287 females and 225 males. The median age at primary surgery was 65 years, range 18 to 96 years. The median observation period was 5 years, range 1 month to 25 years. Sex, age, ulcerated tumor and tumor thickness were found by Cox multivariate regression analysis to act as independent prognostic factors for recurrence-free survival. In addition, size of the excision margin was found of no significance for survival without relapse when adjusting for the independent risk factors.
Inhibition of herpes simplex virus type 1 DNA polymerase activity by peptides from the UL42 accessory protein is largely nonspecific.
To identify regions in the UL42 protein of herpes simplex virus type 1 which affect viral DNA polymerase activity, a series of 96 overlapping pentadecapeptides spanning the entire 488 amino acids of the UL42 protein were synthesized and tested for their ability to inhibit polymerase activity on a primed single-stranded M13 DNA template. Two assays were used: formation of full-length double-stranded M13 molecules and rate of incorporation of deoxyribonucleoside triphosphates. Peptides from five noncontiguous regions of the UL42 protein were found to inhibit herpes simplex virus type 1 polymerase activity in both the presence and absence of UL42 protein. The most active peptides from each region correspond to amino acids 23 to 38 (peptide 6), 64 to 78 (peptide 14), 89 to 102 (peptide 19), 229 to 243 (peptide 47), and 279 to 293 (peptide 57). By two different methods (DNA mobility shift and DNA precipitation), peptides 14, 19, 47, and 57 were found to bind DNA; they most probably inhibit enzyme activity by this mechanism. Peptide 6 did not bind DNA and must act by some mechanism other than competing for DNA. The inhibitory peptides were also tested for activity against mammalian polymerase alpha and the Klenow fragment of Escherichia coli polymerase. Although some limited specificity was demonstrated (up to 10-fold for peptide 6), all the peptides showed significant activity against both polymerase alpha and E. coli polymerase.
[Disease patterns during the first year in the arctic mining industry].
In the zinc, lead and silver ore mine of Maarmorilik, Greenland 1,061 episodes of illness in the first year of employment were studied in 421 persons. Despite the fact that about 80% of the employees were of Scandinavian origin, the patterns of illness were considerably different from the health problems in primary health care units in Denmark. Urogenital problems were the only group of illnesses representing overweight of multiple contact episodes. All other groups of diagnoses were dominated by episodes of single contact. Dental problems, traumatic and urogenital episodes appeared more frequently compared to Danish primary health care units. The lower frequency of traumatic episodes in women reflected their employment in service jobs only. Despite a health examination before employment the total amount of episodes of illness corresponded to that of primary health care units in Denmark, and the age specific contact rate for males was higher than in other morbidity studies from Greenland. Possible explanations were: sick leave required documentation of the doctor, the workload was heavy and prolonged, the spare time possibilities were few, the buildings were inadequate, the employees were isolated from their families for months and the consumption of alcohol was considerable. Because the doctor was the only person with health education in the mining village, knowledge about dental treatment and considerable experience in traumatology and diagnosis of venereal disease were necessary.
Skin melanoma of the head and neck. Prognostic factors and recurrence-free survival in 512 patients.
The clinicopathologic and therapeutic data of 512 patients, with clinical Stage I invasive head and neck melanoma of the skin were retrospectively evaluated. There were 287 females and 225 males. Median age at primary surgery was 65 years (range, 18 to 96 years). Median observation period was 5 years (range, 1 month to 25 years). Site of first recurrence was local in 7% (38 of 512), regional in 13% (67 of 512) and distant in 6% (31 of 512). Sex, age, ulcerated tumor, and tumor thickness were found to act as independent risk factors to recurrence-free survival by Cox multivariate regression analysis. In addition, size of excision margin was found to be of no significance to survival without relapse when adjusting for the independent risk factors.