Diagnosis of systemic causes of uveitis; a matter of ophthalmologist and internist

OBJECTIVE: To assess how often the aetiology is established in patients with uveitis, what systemic disease are found and what is the contribution of the internist to the diagnostic process. DESIGN: Retrospective study. SETTING: University Hospital Leiden, the Netherlands. METHOD: From January 1987 to April 1992, 342 patients presented with uveitis. All patients underwent a standard ophthalmological examination. Referral to an internist and individualised laboratory screening followed in patients with recurrent, chronic, bilateral or panuveitis. Recorded were: ophthalmological data, results of laboratory screening, results of analysis by the internist, final diagnosis and presence of systemic disease. RESULTS: 149 (44%) patients were examined by the internist, 18 (5.2%) were seen by another specialist. In 169 (49%) patients a specific diagnosis was made. 74 (22%) had a systemic disease, 74 a primary ocular disease. In 28 (8%) a systemic disease was presumed (5% were HLA-B27 positive, 3% had abnormal laboratory results); 5 (1%) patients had endophthalmitis as a complication of a septic process. CONCLUSION: In approximately 1/3 of the patients with uveitis a systemic disease was found. Examination by the internist tailored to the individual patient is essential in the evaluation of uveitis patients.     

Optical networks for local loop applications

Some of the options for optical technology within the local loop environment are examined. In particular, passive shared access networks have been considered in some detail. These networks show great promise for delivering existing telephone services to small to medium business customers (4-30 lines) economically by the early 1990s. Extending fiber to the home will also be possible by virtue of a similar passive network infrastructure for customers requiring new broadband services beyond the single telephone line. For one-line plain old telephone service (POTS) customers, an intermediate approach of terminating the fiber network at the final network distribution point, with copper retained for the final leg, may be used prior to the provision of broadband services. A key feature of the passive optical network architecture is the use of wavelength-division multiplexing (WDM) as an upgrade strategy, allowing graceful upgrading from telephone services to multichannel high-definition television (HDTV) on gigabit/second bearers and full two-way switched broadband services employing wavelength routing across the network     

Artefactual cleavage of E coli H-NS by OmpT

In the bacterium Escherichia coli, H-NS-(H1, H1a) is a heat-stable protein with a molecular mass of 15.5 kDa involved in nucleoid organisation and gene regulation linked to certain signal transduction pathways. We have shown that, following addition of preparations of everted inner membrane vesicles, heat-stable cleavage products of approximately 10 kDa of H-NS are formed in vitro from newly synthesised, radio-labelled H-NS and from purified H-NS. The 15.5 kDa protein and its cleavage products were also recovered from a minicell system. These results raised the possibility that cleavage of H-NS is physiologically significant. However, the cleavage of H-NS observed appears to occur during cell breakage and to depend on the method of protein extraction and the presence of the outer membrane protease, OmpT. Nevertheless, the results indicate that H-NS may contain at least two separate domains with cleavage occurring between these domains at a preferred OmpT site. Failure to take account of H-NS cleavage in sample preparation and analysis can lead to serious underestimation of H-NS levels.     

Potentiation of the time-dependent, antidepressant-induced changes in the agonistic behaviour of resident rats by the 5-HT1A receptor antagonist, WAY-100635

Acute and chronic antidepressant drug treatments respectively decrease and increase the aggressive behaviour of resident rats during encounters with unfamiliar conspecifics. We have now examined the effect of the 5-hydroxytryptamine1A receptor antagonist, WAY-100635, on fluoxetine-, paroxetine- or venlafaxine-induced changes in aggression. WAY-100635 (0.1 mg/kg), which did not modify behaviour when given alone, potentiated the venlafaxine (5.54 mg/kg)-induced reduction in aggression after acute treatment and, during chronic treatment, accelerated the fluoxetine (0.34 mg/kg/day)-induced increase in aggression, from day 5 to day 2. A similar change in time course was seen with paroxetine (0.33 mg/kg/day), although the increase in aggression was smaller. Venlafaxine (5.54 mg/kg/day, alone or co-administered with WAY-100635) increased aggression by day 2. During chronic treatment, therefore, venlafaxine, at the dose used, had a more rapid onset of action than either fluoxetine or paroxetine, whereas the fluoxetine- and paroxetine-, but not the venlafaxine-, induced increase in aggression was accelerated by WAY-100635. These studies further support the hypothesis that selective blockade of the 5-hydroxytryptamine1A receptor augments the effects of antidepressant drugs in an animal model predictive of antidepressant activity, presumably by concomitant blockade of the somatodendritic 5-hydroxytryptamine1A autoreceptor-mediated negative feedback system of serotonergic neurones.     

The validity of new memory complaints in the elderly

OBJECTIVE: To determine the validity of new subjective memory complaints (MCs) from individuals who previously, when without dementia, denied having MCs. DESIGN: Prospective cohort. SETTING: Longitudinal, community-based study of aging and dementia. PATIENTS: One hundred thirty-three community-dwelling elderly individuals who were part of a registry for the study of conditions related to aging in North Manhattan, NY. Patients were selected if they were initially without dementia and had completed at least 2 successive annual clinical and neuropsychological evaluations and provided their own medical history. MAIN OUTCOME MEASURES: Performance on memory tests--the Buschke Selective Reminding Test and a visual memory task--and global performance on a neuropsychological test battery and clinical evaluation, by which questionable dementia or dementia was diagnosed according to a well-defined paradigm. RESULTS: Fifty-three subjects with MCs at the initial evaluation performed no worse on the memory test than the 80 subjects who denied MCs initially. There was a weak association between MCs and the diagnosis of questionable dementia at baseline (P = .04), but this was nonsignificant after adjusting for age and education. At 1-year follow-up, 21 of the 80 without baseline MCs now reported MCs. At the follow-up evaluation, these 21 subjects performed significantly worse on the memory tests, were 5 times more likely to have significant cognitive impairment, and had shown significantly greater decline over the preceding year on several of the cognitive measures than the 59 who continued to deny MCs. CONCLUSION: New MCs from individuals, who when without dementia recently denied MCs, may suggest the presence of significant impairment of memory or cognition.     

Estimation of the interindividual variability in the one-compartment pharmacokinetic model for methylmercury: implications for the derivation of a reference dose

A critical step in the U.S. EPA's derivation of an Reference Dose (RfD) for methylmercury is conversion of the maternal hair Hg concentration of 11 ppm to average daily intake using the one-compartment pharmacokinetic model. A default uncertainty factor (UF) adjustment of 3 for interindividual variability was then applied to this conversion. A probabilistic (Monte Carlo) analysis is presented estimating the interindividual variability inherent in this dose conversion for women 18-40 years old based on data in the scientific literature. The dose of 1.1 micrograms/kg/day, calculated by the U.S. EPA to correspond to 11 ppm Hg in hair, is estimated in this analysis to be larger than 94-99% of corresponding doses. The application of a UF of 3 to this U.S. EPA value gives a dose which is estimated to be larger than 28-73% of corresponding doses. This analysis suggests that if the dose conversion in the RfD is intended to be inclusive of 95-99% of women 18-40, the daily intake should be set at 0.1-0.3 microgram/kg/day. The RfD of 0.03-0.1 microgram/kg/day, derived from this dose by the U.S. EPA's application of an additional UF of 3 for additional toxicologic concerns, is somewhat smaller than the current RfD of 0.1 microgram/kg/day.     

Partial cricotracheal resection with primary anastomosis in the pediatric age group

The traditional approach to severe subglottic stenosis (SGS) in the pediatric age group is laryngotracheal reconstruction (LTR). This approach may be complex and multistaged, with variable and unpredictable success rates in the individual patient. Excellent results have been reported in adults who had severe SGS and underwent partial resection of the cricoid and primary thyrotracheal anastomosis. This procedure has not been widely reported in infants and children. We report our experience with this procedure in 16 pediatric patients with grade III or IV SGS. Eleven patients had multiple previous LTR operations. The preoperative evaluation, surgical techniques, postoperative care, complications, and final results are described and discussed. Fourteen patients were decannulated after the procedure, 1 patient needed a second open procedure prior to decannulation, and 1 patient with concomitant bronchopulmonary dysplasia remains cannulated, for an overall 94% decannulation rate. Fourteen patients have no limitation of respiration, and 1 patient has moderate exercise intolerance. The results of this series suggest that partial cricotracheal resection with primary anastomosis is a relatively safe and effective procedure for pediatric patients with severe SGS.     

Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors

The majority of pituitary tumors are of monoclonal origin; however, the molecular basis for their formation is poorly understood. Somatic mutations in the alpha-subunit of the GTP-binding protein, Gs alpha (gsp oncogene) have been found in about one third of GH-secreting tumors. Mutations in another alpha-subunit of a GTP-binding protein, Gi2 alpha (gip mutations) have been described in other endocrine tumors. In this study, we examined 21 nonfunctioning pituitary tumors and 4 macroprolactinomas for gsp mutations and 27 nonfunctioning tumors and 4 macroprolactinomas for gip mutations. Using the polymerase chain reaction and denaturing gradient gel electrophoresis, 2 nonfunctioning pituitary tumors displayed migration abnormalities when the Gs alpha-gene was analyzed. Sequence analysis of these abnormally migrating polymerase chain reaction products revealed two previously known gsp mutations: arginine at codon 201 altered to cysteine, and glutamine at codon 227 changed to leucine. No gip mutations could be demonstrated. These findings emphasize the monoclonal origin of nonfunctioning pituitary tumors and suggest that cAMP may play a role in tumorigenesis of nonfunctioning pituitary tumors.     

Making darkness visible: the discovery of X-ray and its introduction to dentistry

Wilhelm Conrad Roentgen's discovery of the X-ray one century ago has been ranked in importance with the discovery and development of anesthesia and the discovery of microorganisms and their role in disease. Roentgen's scientific devotion and the persistence of C. Edmund Kells, who took Roentgen's discovery and applied it to dentistry, had a great impact on how dentists practice today.