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Biomedical subjects

M Wall

Publications and source records attributed to M Wall.

At least 19 recordsLinked to original sources

Risk factors for work related violence in a health care organization.

OBJECTIVE: Identify the exposure effects of job family, patient contact, and supervisor support on physical and non-physical work related violence. DESIGN: Cross sectional study of employees in a Midwest health care organization, utilizing a specially designed mailed questionnaire and employer secondary data. SUBJECTS: Respondents included 1751 current and former employees (42% response rate). RESULTS: Physical and non-physical violence was experienced by 127 (7.2%) and 536 (30.6%) of the respondents, respectively. Multivariate analyses of physical violence identified increased odds for patient care assistants (odds ratio (OR) 2.5, 95% confidence interval (CI) 1. 1 to 6.1) and decreased odds for clerical workers (OR 0.1, 95% CI 0.03 to 0.5). Adjusted for job family, increased odds of physical violence were identified for moderate (OR 5.9, 95% CI 2.1 to 16.0) and high (OR 7.8, 95% CI 2.9 to 20.8) patient contact. Similar trends were identified for non-physical violence (OR 1.4, 95% CI 1.1 to 2.0 and OR 1.7, 95% CI 1.3 to 2.3). Increased supervisor support decreased the odds of both physical (OR 0.7, 95% CI 0.6 to 0.95) and non-physical violence (OR 0.5, 95% CI 0.4 to 0.6), adjusting for job family and demographic characteristics. CONCLUSIONS: Increased odds of physical violence were identified for the job family of nurses, even when adjusted for patient contact. Increased patient contact resulted in increased physical and non-physical violence, independent of job family, while supervisor support resulted in decreased odds of physical and non-physical violence.

Cross-Sectional Studies↗

Effect of severity of myocardial failure on heart rate variability in Doberman pinschers with and without echocardiographic evidence of dilated cardiomyopathy.

OBJECTIVE: To determine whether heart rate variability (HRV) is reduced in Doberman Pinschers with dilated cardiomyopathy. DESIGN: Case series. ANIMALS: 62 overtly healthy Doberman pinschers. PROCEDURE: Heart rate variability was analyzed in time and frequency domains from data obtained during 24-hour ambulatory electrocardiographic Holter recordings in 41 overtly healthy Doberman pinschers with normal echocardiograms and 21 overtly healthy Doberman pinschers with abnormal echocardiograms. RESULTS: Heart rate variability usually was greater during night versus day, and 2 dogs with the most severe myocardial failure had reduced HRV. CONCLUSIONS AND CLINICAL RELEVANCE: Reduced HRV was detected only in Doberman Pinschers with the most severe myocardial failure. Thus, HRV in less severely affected dogs is not reduced, or the normal sinus arrhythmia of dogs renders HRV relatively insensitive. Analysis of HRV did not provide additional information relative to the severity of left ventricular dysfunction or risk of sudden death from that which could be derived from echocardiography, analysis of Holter recordings, and signal-averaged electrocardiography.

Animals↗

Results of ambulatory electrocardiography in overtly healthy Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy.

OBJECTIVE: To determine results of ambulatory electrocardiography in and outcome of overtly healthy Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy. DESIGN: Case series. ANIMALS: 44 overtly healthy (25 male, 19 female) Doberman Pinschers. PROCEDURE: 24-hour ambulatory electrocardiographic (Holter) recordings with > 90% scan quality obtained the same day that echocardiography was performed were reviewed. RESULTS: Holter recordings from 42 of 44 (95%) dogs contained ventricular premature complexes (VPC). Fifteen of 44 (34%) dogs had > 100 VPC, 9 (20%) had > 500 VPC, and 5 (11%) had > 1,000 VPC. Nonsustained (< 30 seconds) ventricular tachycardia was detected in 4 dogs. Eighteen of 27 (67%) dogs with > 100 VPC, any couplets or triplets of VPC, or ventricular tachycardia developed dilated cardiomyopathy within 1 year, compared with 8 of 17 (47%) dogs with < 100 VPC, no couplets or triplets of VPC, and no ventricular tachycardia. Of the 18 dogs that did not develop dilated cardiomyopathy within 1 year, 11 (61%) did so within 3 years. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a high percentage of Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy will be found to have VPC during 24-hour ambulatory electrocardiography and that most will develop echocardiographic abnormalities indicative of cardiomyopathy.

Animals↗

Evaluation of the catalytic mechanism of AICAR transformylase by pH-dependent kinetics, mutagenesis, and quantum chemical calculations.

The catalytic mechanism of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (AICAR Tfase) is evaluated with pH dependent kinetics, site-directed mutagenesis, and quantum chemical calculations. The chemistry step, represented by the burst rates, was not pH-dependent, which is consistent with our proposed mechanism that the 4-carboxamide of AICAR assists proton shuttling. Quantum chemical calculations on a model system of 5-amino-4-carboxamide imidazole (AICA) and formamide using the B3LYP/6-31G level of theory confirmed that the 4-carboxamide participated in the proton-shuttling mechanism. The result also indicated that the amide-assisted mechanism is concerted such that the proton transfers from the 5-amino group to the formamide are simultaneous with nucleophilic attack by the 5-amino group. Because the process does not lead to a kinetically stable intermediate, the intramolecular proton transfer from the 5-amino group through the 4-carboxamide to the formamide proceeds in the same transition state. Interestingly, the calculations predicted that protonation of the N3 of the imidazole of AICA would reduce the energy barrier significantly. However, the pK(a) of the imidazole of AICAR was determined to be 3.23 +/- 0.01 by NMR titration, and AICAR is likely to bind to the enzyme with its imidazole in the free base form. An alternative pathway was suggested by modeling Lys266 to have a hydrogen-bonding interaction with the N3 of the imidazole of AICAR. Lys266 has been implicated in catalysis based on mutagenesis studies and the recent X-ray structure of AICAR Tfase. The quantum chemical calculations on a model system that contains AICA complexed with CH3NH3+ as a mimic of the Lys residue confirmed that such an interaction lowered the activation energy of the reaction and likewise implicated the 4-carboxamide. To experimentally verify this hypothesis, we prepared the K266R mutant and found that its kcat is reduced by 150-fold from that of the wild type without changes in substrate and cofactor Km values. The kcat-pH profile indicated virtually no pH-dependence in the pH range 6-10.5. The results suggest that the ammonium moiety of Lys or Arg is important in catalysis, most likely acting as a general acid catalyst with a pK(a) value greater than 10.5. The H267A mutant was also prepared since His267 has been found in the active site and implicated in catalysis. The mutant enzyme showed no detectable activity while retaining its binding affinity for substrate, indicating that it plays a critical role in catalysis. We propose that His267 interacts with Lys266 to aid in the precise positioning of the general acid catalyst to the N3 of the imidazole of AICAR.

Binding Sites↗

Penetrating esophageal injuries: multicenter study of the American Association for the Surgery of Trauma.

OBJECTIVE: The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS: This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fisher's exact test, Student's T test, and logistic regression analysis. RESULTS: The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION: Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

Adolescent↗

SITA standard in optic neuropathies and hemianopias: a comparison with full threshold testing.

PURPOSE: To compare visual sensitivity, fatigue effect, and probability plot data between Full Threshold (FT) Humphrey automated perimetry and Swedish Interactive Threshold Algorithm (SITA) standard strategies in patients with optic neuropathies and hemianopias. METHODS: Twenty-four patients with nonglaucomatous optic neuropathies and 18 patients with a relative homonymous or bitemporal hemianopia were tested with both conventional perimetry (Humphrey 24-2 program) and "back to back" SITA standard tests (SITA 1, SITA 2) to approximate the test time of the FT test conditions. Also, 28 normal subjects between the ages of 20 and 80 were tested with this protocol. The visual field quadrants with the most damage were used to evaluate any fatigue effect (i.e., possible lack of fatigue effect with SITA standard due to the shorter test time) and to compare probability plot data between FT, SITA 1, and SITA 2. Pointwise total and pattern deviation probability plot defects were weighted by degree of significance and summed. RESULTS: Test times for normal subjects were 45 seconds longer for FT than for the combined test time of SITA 1 + SITA 2. Patients' test times were 40 seconds longer for hemianopias and 90 seconds longer for optic neuropathies with FT than the combined times for two SITA tests. There were higher sensitivities found with SITA 1 compared with Full Threshold (1.06 dB, P< 0.001) and SITA 2 with Full Threshold (0.73 dB, P< 0.001) in the most damaged quadrant for the optic neuropathy patients; for the hemianopia patients the difference in values were between SITA 1 and Full Threshold (0.96 dB, P = 0.07) and between SITA 2 and Full Threshold (0.11 dB, P = 0.87). The second SITA standard test had lower sensitivity than the first SITA standard test by 0.82 dB in hemianopias and by 0.71 dB in optic neuropathy patients. Analysis of the total and pattern deviation probability plot data showed slightly more defects (number and magnitude) with SITA 1 compared to FT for both groups, but the differences were not statistically significant. CONCLUSIONS: Sensitivities were higher in patients with hemianopias or optic neuropathies using SITA standard compared with FT by approximately 1 dB. The probability plot comparison suggests SITA standard is at least as good as FT for detection of visual loss in individual examinations. However, efficacy of SITA standard for serial examinations has not yet been evaluated.

Adult↗

Human AICAR transformylase: role of the 4-carboxamide of AICAR in binding and catalysis.

We have prepared 4-substituted analogues of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to investigate the specificity and mechanism of AICAR transformylase (AICAR Tfase). Of the nine analogues of AICAR studied, only one analogue, 5-aminoimidazole-4-thiocarboxamide ribonucleotide, was a substrate, and it was converted to 6-mercaptopurine ribonucleotide. The other analogues either did not bind or were competitive inhibitors, the most potent being 5-amino-4-nitroimidazole ribonucleotide with a K(i) of 0.7 +/- 0.5 microM. The results show that the 4-carboxamide of AICAR is essential for catalysis, and it is proposed to assist in mediating proton transfer, catalyzing the reaction by trapping of the addition compound. AICAR analogues where the nitrogen of the 4-carboxamide was derivatized with a methyl or an allylic group did not bind AICAR Tfase, as determined by pre-steady-state burst kinetics; however, these compounds were potent inhibitors of IMP cyclohydrolase (IMP CHase), a second activity of the bifunctional mammalian enzyme (K(i) = 0.05 +/- 0.02 microM for 4-N-allyl-AlCAR). It is proposed that the conformation of the carboxamide moiety required for binding to AICAR Tfase is different than the conformation required for binding to IMP CHase, which is supported by inhibition studies of purine ribonucleotides. It is shown that 5-formyl-AICAR (FAICAR) is a product inhibitor of AICAR Tfase with K(i) of 0.4 +/- 0.1 microM. We have determined the equilibrium constant of the transformylase reaction to be 0.024 +/- 0.001, showing that the reaction strongly favors AICAR and the 10-formyl-folate cofactor. The coupling of the AICAR Tfase and IMP CHase activities on a single polypeptide allows the overall conversion of AICAR to IMP to be favorable by coupling the unfavorable formation of FAICAR with the highly favorable cyclization reaction. The current kinetic studies have also indicated that the release of FAICAR is the rate-limiting step, under steady-state conditions, in the bifunctional enzyme and channeling is not observed between AICAR Tfase and IMP CHase.

Adenosine Monophosphate↗

Improved general health status in an unselected infant population following an allergen-reduced dietary intervention programme: the ZUFF-STUDY-PROGRAMME. Part II: infant growth and health status to age 6 months. ZUg-FrauenFeld.

AIM OF THE STUDY: An allergen-reduced dietary intervention programme with strict dietary requirements was implemented over the first four months of life in an unselected population-based infant cohort and compared to a non-intervention cohort (the ZUFF study). Recommendations for the dietary programme in the intervention cohort were extended, but not strictly implemented, until the end of month six. The intervention was based on breastfeeding, a moderate whey hydrolysate formula (pHF), and delayed introduction of weaning foods with a high allergenicity. This study was a prospective, controlled, and unblinded study, the first to assess the effects of an allergen-reduced, pHF-based early nutritional programme in a broad unselected infant population. Because overall healthy development of the infant is a major objective of any nutritional programme, the study evaluated the effects of the dietary intervention on infant growth and general health status rather than specific allergic manifestations. Part I of this paper gave results for nutritional behaviour only, and Part II gives results for growth and general health status during the intervention period through the sixth month of life. METHODS: Assignment of study infants was to demographically comparable intervention (Z) or control (FF) cohorts according to place of birth. In the intervention cohort (Z=564), the recommended dietary regimen was breastfeeding and--if exclusive breastfeeding was not possible--supplementation with a moderately hydrolysed, allergen-reduced infant formula (pHF). Weaning foods were delayed until four months of age or later in case of weaning foods with high allergenicity. In the control cohort (FF=566), there was no specific intervention. Imbalances between cohorts in confounding (adjuvant) factors that could influence health-related outcomes were integrated as covariates into the logistic regression of the main analyses. Growth parameters included weight, length, head circumference, BMI, and Z scores (SDS). General health status was assessed by clinically significant findings in gastrointestinal, respiratory, or skin symptoms. RESULTS: Growth at 6 weeks and at 3 and 6 months was similar for Z and FF. Significantly fewer Z than FF infants had clinically noteworthy health findings at 3 months (Z=27% versus FF=37%, odds ratio=0.63, CI=0.48-0.82) and 6 months (Z=33% versus FF=49%, odds ratio=0.51, CI= 0.40-0.66). This corresponds to a 30 % reduction in overall health concerns at 6 months for the intervention cohort. At 3 and 6 months, differences between cohorts in most measures of general health status were strongly influenced by a lower incidence of skin symptoms in the Z cohort. Within FF, there were fewer exclusively breastfed (eBF) infants with health problems at 3 months compared with those who were partially (pBF) or non-breastfed (nBF) (eBF=31%, pBF=40%, nBF=39%, p< 0.05). In contrast, in the Z intervention cohort, the number of infants with health concerns was similar for exclusively breastfed infants and for those in whom mother's milk was supplemented or replaced by pHF (eBF=29%, pBF=25%, nBF=26%, ns). In a subanalysis of overall health findings in infants without a family risk of allergies, there were again significantly fewer Z than FF infants with any health or any skin problem. CONCLUSION: An allergen-reduced dietary recommendation that includes a moderate whey hydrolysate infant formula (pHF) has no negative effects on growth parameters up to 6 months of life in an infant population unselected for atopic risk. The dietary intervention produced improvements in general health status when compared with a control cohort that received infant formula with unhydrolysed proteins (IF), and high allergenic weaning foods at an earlier age. The difference between cohorts was principally due to fewer adverse skin findings. (ABSTRACT TRUNCATED)

Animals↗

Improved general health status in an unselected infant population following an allergen reduced dietary intervention programme. The ZUFF-study-programme. Part I: Study design and 6-month nutritional behaviour.

BACKGROUND: The best nutritional option for newborn infants is mother's milk. However, some newborn babies may not be exclusively breastfed during the first months of life, potentially leading to reduced overall health status and the early onset of allergic diseases in some infants. Considerable research has been devoted to the development and assessment of infant nutrition programmes, particularly to the prevention of allergies in high-risk infants. However, equal numbers of infants with and without an elevated familial risk of allergies will eventually develop allergic diseases. Therefore, optimizing nutritional programmes for the early infant population as a whole is an important--but as yet insufficiently studied--area of investigation. Moreover, although safe and effective nutrition must primarily support healthy development of the infant, few studies have evaluated the overall health benefits of nutritional interventions, but have focussed on specific allergic manifestations. In animal models, an allergen-reduced moderate whey hydrolysate formula (pHF, Nestlé Beba HA) induces the development of oral tolerance towards cow's milk proteins, without inducing sensitization. In infants with a high risk for allergies, pHF formulae reduce the early onset of allergic disease during the first 5 years of life by approximately 50% compared with a dietary regimen of unaltered proteins. At present, very little is known about the overall health benefits of such a dietary intervention on the unselected infant population as a whole. AIM OF THE STUDY: The aim of our prospective, controlled study was to investigate the overall health benefits of an allergen-reduced nutritional programme in a newborn infant population unselected for atopic risk factors. The population in our study was as comparable as possible to the general population of healthy newborn infants. Our study included exclusive breastfeeding, use of a moderate whey hydrolysate formula (pHF, Nestlé Beba HA) if infant formula was needed, and delayed introduction of low-allergenic weaning foods. The study included assessments of compliance with the dietary programme, and evaluated nutritional habits, growth, and overall health status for 24 months. The health evaluation included allergic manifestations but did--by porpose--not define or evaluate them specifically. Part I of this paper gives results for nutritional habits during the first 6 months of life, Part II gives results for growth and general health status for the same time period, Part III will present feeding habits during the second half of the first year of life, and Part IV will present results to 24 months of age. The complete study report is published as a supplement to this journal. METHODS: Nutritional assignment was to demographically comparable intervention (Z) or control (FF) cohorts according to the infant's place of birth. In the intervention cohort (Z, n = 564), the recommended dietary regimen was breastfeeding and/or the pHF formula, with no weaning food before 4 months of age. In the control cohort (FF, n = 566), there was no intervention. Longitudinal diet groups, defined for 4 months, excluding dropouts and noncompliants, were exclusive breastfeeding (eBF, Z, n = 201, FF, n = 162), partial breastfeeding (pBF, Z, n = 222, FF, n = 311), or non-breastfeeding (nBF, Z, n = 43, FF, n = 62). Imbalances between groups and cohorts in confounding factors that could influence health-related symptoms were integrated as covariates into the main analyses using logistic regression. Nutritional surveillance was carried out using continuous prospective monitoring. RESULTS: The overall rate of breastfeeding, irrespective of partial or exclusive breastfeeding or the additional use of weaning foods, was similar in both cohorts at 4 and 6 months. However, from ages 3 to 6 months, significantly more Z than FF infants were exclusively breastfed (p < 0.05), and weaning foods were introduced at a significantly later age in Z t

Animals↗

Prolonged use of intraluminal arterial shunts without systemic anticoagulation.

BACKGROUND: Temporary arterial shunts maintain perfusion while surgeons postpone arterial repairs. The common indications are combined orthopedic and vascular injuries and damage control. The duration of patency and the need for systemic anticoagulation remain in question. We examined our experience for answers. METHODS: We searched for patients who had temporary arterial shunts and collected the following: mechanism, artery injured, shunt time, blood loss and transfusions, injury severity score (ISS,) mangled extremity severity score (MESS,) and anticoagulation. RESULTS: Of 19 patients, 10 had shunts for damage control (group 1,) and 9, for orthopedic/vascular injuries (group 2.) group 1 had significantly higher shunt time, mortality, ISS, and MESS. Shunt time ranged from 47 to 3,130 minutes (52 hours.) Two patients, 1 in each group, required amputations. CONCLUSION: Temporary arterial shunts can be use for combined orthopedic and vascular injuries and for damage control. Shunts can stay open for 52 hours without systemic anticoagulation.

Adolescent↗

Is regionalization of trauma care using telemedicine feasible and desirable?

BACKGROUND: The judgement and skill of an experienced surgeon are crucial ingredients during trauma resuscitation, so that errors of omission, commission, and misprioritization can be avoided. Trauma represents a potential paradigm application for telemedicine owing to its ubiquitous and urgent nature and the limited availability of specialized care. METHODS: A two-phase project was performed, using an Advanced Trauma Life Support (ATLS)-based evaluation tool. In phase I, we reviewed 24 videotaped trauma resuscitations on a single pass. Clinical data thus observed were compared with the clinical chart for agreement. In phase II, we performed real time, remote, initial evaluations of 17 trauma victims. RESULTS: In phase I, 19 of 44 variables had agreement rates >90%, 10 had agreement rates between 70% and 90%. In phase II, agreement rates were similar to those in phase I, with improved accuracy in documenting initial and secondary vital signs and the secondary physical examination. CONCLUSION: Remote evaluation of trauma victims is feasible. Accurate clinical data can be recorded, tasks delegated, and therapeutic measures advised using telemedicine. This can make expert trauma care available to hospitals without advanced trauma systems and potentially reduce cost, prevent unnecessary transfers, and promote early transfer when indicated.

Feasibility Studies↗

Quantitative phase-sensitive imaging in a transmission electron microscope

This paper presents a new technique for forming quantitative phase and amplitude electron images applicable to a conventional transmission electron microscope. With magnetised cobalt microstructures used as a test object, we use electron holography to obtain an independent measurement of the phase shift. After a suitable calibration of the microscope, we obtain quantitative agreement of the phase shift imposed on the 200 keV electrons passing through the sample.

Journal Article↗

Effect of instructions on conventional automated perimetry.

PURPOSE: To investigate the effect of perimetrists' instructions on automated perimetry thresholds. METHODS: Eighteen volunteers in two age groups participated in a series of three test sessions. Each session consisted of a Humphrey Field Analyzer 30-2 test, a questionnaire, and a customized test program using a Humphrey perimeter to construct frequency of seeing (FOS) curves from which thresholds were calculated, and a descriptive measure of response criterion was derived. The FOS curves were obtained at a central and a peripheral test location within the same test session. The three test sessions differed only by the instructions given. The instructions were adapted from those listed in the manufacturer's instruction manual and were designed to influence participants to respond to the stimuli in a conservative, liberal, or neutral manner. RESULTS: For the 30-2 threshold test, a significant difference in mean deviation was found among the three instruction types (P = 0.001) and between the two age groups (P = 0.001). Although differences were small in the younger subjects (2.04 dB), the means for the responses from liberal to conservative differed by 6.57 dB in the older subjects. Thresholds obtained in a peripheral location by the customized threshold test were found to differ significantly between the age groups (younger group mean, 31.0 dB; older group mean, 27.2 dB) and among the instruction types (liberal mean, 30.9 dB; conservative mean, 28.1 dB; and neutral mean, 30.3 dB; P < 0.001). The descriptive measurement of response criterion suggests that a difference in criteria occurred as a result of the instructions in both peripheral and central locations for both age groups (P = 0.0001). In addition, according to self-reports, liberal instructions caused participants to be more likely to respond, whereas the conservative instructions caused them to be more reluctant to respond. CONCLUSIONS: Perimetrists' instructions can significantly affect obtained automated perimetry thresholds.

Adult↗

Idiopathic intracranial hypertension: mechanisms of visual loss and disease management.

Idiopathic intracranial hypertension (IIH) is a disorder of increased intracranial pressure of unknown cause. It is a disorder, predominantly of overweight women in the childbearing years. The major morbidity of the disease is visual loss. Damage to the visual system occurs at the optic nerve head. This damage is most likely due to axoplasm flow stasis and resultant intraneuronal ischemia. Management of IIH begins with educating the patient about the disease and its potential outcomes. I recommend modest dieting and following a low-salt regimen with caution against overuse of fluids. Acetazolamide and Lasix appear to be efficacious. Patients failing medical therapy have optic nerve sheath fenestration performed if visual loss is the main morbidity. Shunting procedures are considered if headache is the main symptom. Most patients respond well to therapy, but idiopathic intracranial hypertension may recur throughout life.

Age Factors↗

Production of cyclic peptides and proteins in vivo.

Combinatorial libraries of synthetic and natural products are an important source of molecular information for the interrogation of biological targets. Methods for the intracellular production of libraries of small, stable molecules would be a valuable addition to existing library technologies by combining the discovery potential inherent in small molecules with the large library sizes that can be realized by intracellular methods. We have explored the use of split inteins (internal proteins) for the intracellular catalysis of peptide backbone cyclization as a method for generating proteins and small peptides that are stabilized against cellular catabolism. The DnaE split intein from Synechocystis sp. PCC6803 was used to cyclize the Escherichia coli enzyme dihydrofolate reductase and to produce the cyclic, eight-amino acid tyrosinase inhibitor pseudostellarin F in bacteria. Cyclic dihydrofolate reductase displayed improved in vitro thermostability, and pseudostellarin F production was readily apparent in vivo through its inhibition of melanin production catalyzed by recombinant Streptomyces antibioticus tyrosinase. The ability to generate and screen for backbone cyclic products in vivo is an important milestone toward the goal of generating intracellular cyclic peptide and protein libraries.

Bacterial Proteins↗