Reevaluating the carcinogenicity of ortho-toluidine: A new conclusion and its implications

The aromatic amine ortho-toluidine has been recognized by IARC as an animal carcinogen for the past decade. Three recent epidemiological studies of worker populations have now implicated this chemical as a human bladder carcinogen. In a study by E. Ward, A. Carpenter, S. Markowitz, D. Roberts, and W. Halperin ((1991), J. Natl. Cancer Inst. 83, 501–506), workers definitely exposed to ortho-toluidine for at least 10 years experienced a Standardized Incidence Ratio (SIR) of 27.2 (90% CI = 11.8–53.7). The other major exposure was to aniline, which significant epidemiological studies have failed to confirm as a human carcinogen. In retrospect, studies by G. F. Rubino, G. Scansetti, G. Piolatto ((1982) Environ. Res. 27, 241–254) and M. J. Stasik ((1988) Int. Arch. Occup. Environ. Health 60, 21–24) also support the hypothesis that ortho-toluidine is a human bladder carcinogen. Animal studies of both ortho-toluidine and its possible confounders in these epidemiological investigations further confirm this hypothesis. When evaluated in a suitably comprehensive way, according to the traditional standards for assessing causality outlined by A. B. Hill ((1977) A Short Textbook of Medical Statistics, pp. 288–294, Lippincott, Philadelphia) the evidence that ortho-toluidine causes human bladder cancer has become much more conclusive. In this case, animal tests have proven a good predictor of human carcinogenicity.     

Cervical Anterior Spinal Cord Infarction

Spinal cord infarction or ischemia predominates in the thoracic region, less so in the cervical and lumbar regions. Different etiological factors have been implicated in anterior spinal artery syndrome. Magnetic resonance imaging (MRI) allows in vivo imaging of spinal cord disease, including infarction. A 31-yearold, previously healthy man had an acute onset of interscapular pain, followed by rapid development of quadriparesis associated with paresthesias and mild bladder dysfunction. Initial MRI of the cervicothoracic region demonstrated normal findings. A repeat study obtained 6 days later showed marked increase in the cervical cord size, especially at the C6-7 level. On the T2-weighted sagittal series and after gadolinium injection, increased signal in the anterior portions of the cord extending from C-4 to the T2-3 interspace was noted. This was most prominent at the C-6 and C-7 levels. The coronal views revealed abnormal high signal in the region of the anterior horns of the gray matter, a finding that is recognized as an “owl's eyes” pattern. Because the MRI changes of cerebral infarction may succeed a clinical event by hours or days, accurate diagnosis may require delayed or repeated studies. This report suggests that the diagnosis of spinal cord disease requires a similar evaluation.     

Prodromal frontal/executive dysfunction predicts incident dementia in Parkinson's disease.

To identify the cognitive characteristics predictive of incident dementia in Parkinson's disease (PD), we examined the baseline neuropsychological profiles of 18 initially non-demented patients with PD who met diagnostic criteria for dementia (PDD) at one-year follow-up. PDD participants' baseline neuropsychological test scores were compared to the baseline performance of 18 patients with PD who did not meet criteria for dementia at one-year follow-up (PDND) and 18 normal controls (NC). The three groups were matched on baseline demographic and disease variables. Relative to the PDND group, the incident PDD participants demonstrated significantly poorer performance on digits backward (Wechsler Memory Scale-Revised), word list learning and recognition (California Verbal Learning Test), and perseverative errors on the Wisconsin Card Sorting Test. Each of these baseline neuropsychological variables exhibited adequate diagnostic classification accuracy in predicting PDD and PDND group membership at follow-up. These results suggest that subtle frontal/executive dysfunction is evident during the immediate PDD prodrome and may be of prognostic value in identifying PD patients at risk for dementia. Accordingly, neuropsychological evaluation may facilitate early identification of PDD and thereby inform appropriate dispositional planning.     

Promoting Pneumococcal Immunizations Among Rural Medicare Beneficiaries Using Multiple Strategies

CONTEXT: Vaccine-preventable diseases among adults are major contributing causes of morbidity and mortality in the United States. However, adult immunizations continue to be underutilized in both urban and rural areas. PURPOSE: To evaluate the effectiveness of a community-wide education campaign and mailed reminders promoting pneumococcal immunizations to rural Medicare beneficiaries. METHODS: We implemented a community-wide education campaign, and mailed reminders were sent to Medicare beneficiaries in 1 media market in Montana to increase pneumococcal immunizations. In a second distinct media market, mailed reminders only were sent to beneficiaries. FINDINGS: The proportion of respondents aged 65 years and older aware of pneumococcal immunizations increased significantly from baseline to follow-up among respondents both in the education-plus-reminder (63% to 78%, P = 0.04) and the reminder-only (64% to 74%, P = 0.05) markets. Overall from 1998 to 1999, there was a 3.7-percentage-point increase in pneumococcal immunization claims for Medicare beneficiaries in the education-plus-reminder market and a 1.5-percentage-point increase in the reminder-only market. Medicare beneficiaries sent reminders in the education-plus-reminder market compared to those in the reminder-only market were more likely to have a claim for pneumococcal immunization in 1999 (odds ratio 1.18, 95% confidence interval 1.08 to 1.28). The results suggest that these quality improvement strategies (community education plus reminders and reminders alone) modestly increased pneumococcal immunization awareness and pneumococcal immunization among rural adults. Mailed reminder exposure was associated with an increased prevalence of pneumococcal immunizations between 1998 and 1999 and was augmented somewhat by the education campaign.     

Asthma in New Zealand: implications for North America

In the early 1980s, reports of a significant rise in asthma mortality emanated from New Zealand. Difficulties in accessing medical care, noncompliance with medication, inadequate medical management, lack of patient education, and inadequate recognition of asthma severity have been suggested as factors that may have contributed to the excess of asthma mortality. Asthma mortality has now declined significantly in New Zealand. We traveled to New Zealand to examine why the incidence of asthma deaths declined in that country at the time where it may have continued to rise in North America. We hypothesize that increased patient and physician education, targeting of high-risk socioeconomic groups, and increased public awareness have played a large role in these improved statistics. The measures taken in New Zealand which have involved a cooperative approach between lay organizations, the pharmaceutical industry, government agencies, and medical personnel may be adapted to North America with, it is hoped, similar results.     

Corticotropin-Releasing Factor Reduces Lipopolysaccharide-Induced Pulmonary Vascular Leak

Previous studies have suggested that corticotropin-releasing factor (CRF) has immunoregulatory effects in addition to its neuroendocrine role. We examined the ability of CRF to inhibit lipopolysaccharide (LPS)-induced pulmonary vascular leak in vivo. Female BALB/C mice were treated with either normal saline (NS) or CRF prior to injection with LPS. Pulmonary vascular leak was inhibited by CRF as assessed by measurement of lung wet-to-dry ratios. The stress-induced increase in serum corticosterone levels in mice injected with LPS alone was not further increased by treatment with CRF. This indicates that the effect of CRF was not mediated centrally by stimulation of endogenous steroid release. Histologic examination of the lungs revealed that leukocyte infiltration was significantly depressed in CRF-treated mice thus confirming the protective effect of CRF. In addition, a modest prolongation of survival was demonstrated in CRF-treated mice following challenge with LPS (p=.08). These data indicate the potential utility of CRF as a modulator of pulmonary vascular leak.     

Characterization of Aerosols of Human Recombinant Deoxyribonuclease I (rhDNase) Generated by Jet Nebulizers

Recombinant human deoxyribonuclease I (rhDNase) is a new therapeutic agent developed to improve clearance of purulent sputum from the human airways. It is delivered by inhalation. Four jet nebulizers, T Up-Draft II (Hudson), Customized Respirgard II (Marquest), Acorn II (Marquest), and Airlife Misty (Baxter), were evaluated in vitro for their ability to deliver aerosols of rhDNase. The aerosols were generated from 2.5-mL aqueous solutions of rhDNase, at concentrations of either 1 or 4 mg/mL. In all experiments, the Pulmo-Aide Compressor (De Vilbiss) was used to supply the air to the nebulizers. Between 20 and 28% of the rhDNase dose initially placed in the nebulizers was delivered to the mouthpiece in the respirable range (1-6 µm). Evaluation of the rhDNase following nebulization in all four devices indicated that there was no loss in enzymatic activity and no increase in aggregation. Circular dichroism spectrophotometry indicated there was no change in either the secondary or the tertiary structure in rhDNase following nebulization. These results show that all four nebulizers are essentially equivalent in their ability to deliver respirable doses of rhDNase in an intact, fully active form. Changing the concentration of the solution in the nebulizer from 4 to 1 mg/mL rhDNase leads to a proportional reduction in the respirable dose delivered to the mouthpiece.     

Moderne Pharmakotherapie bei supraventrikulären und ventrikulären Herzrhythmusstörungen

Currently the pharmacological approach still represents the mainstay in the acute phase of arrhythmia management as well as in the chronic treatment phase of specific entities such as atrial fibrillation. However, non-pharmacological options have recently emerged as frequently used first-line tools for the treatment of various supraventricular and ventricular heart rhythm disturbances. Nevertheless, antiarrhythmic drug treatment is frequently used as a bridging or adjunctive therapy in conjunction with catheter ablation or implantable cardioverter defibrillators. Antiarrhythmic agents constitute a very heterogeneous group prone to various drug interactions and side-effects. Therefore, this article aims to summarise the most important facts and recent findings with regard to appropriate contemporary pharmacological therapy of atrial and ventricular arrhythmias in clinical practice.