Effects of the anticholinesterase edrophonium on spectral analysis of heart rate and blood pressure variability in humans.

Edrophonium, an anticholinesterase, exerts a biphasic effect on cardiovascular autonomic drive in humans (lower doses enhance; higher doses reduce). Twenty-five anesthetized, mechanically respired (10 breaths. min(-1), constant tidal volume) patients were given either saline (n = 10) or edrophonium (0.01-1.0 mg. kg(-1), n = 15) following surgery. ECG, radial arterial pressure, and respiratory rate were sampled at 250 Hz to obtain time series for consecutive R-R intervals (RRIs), and systolic (SBP) and diastolic blood pressure (DBP). A Wigner distribution was used for time frequency mapping of spectral powers at high (HFP, 0.15-0.5 Hz) and low (LFP, 0.0-0.05 Hz) frequency. Edrophonium produced a dose-dependent decrease in heart rate [baseline 66.8 +/- 1.9 (S.E.M.) beats per minute; maximum decrease to 55.8 +/- 1.4 beats per minute with 1.0 mg. kg(-1), P < 0.01]. HFP of the RRI increased at low doses (0.2-0.4 mg. kg(-1); maximum increase to 111.0 +/- 58.2% baseline; P < 0.01) but decreased (-49.5 +/- 35.5% baseline; P < 0.01) at higher (1.0 mg. kg(-1)) doses. Edrophonium had no effect on SBP and DBP. HFP of SBP decreased with increasing doses (maximal decrease to -26.2 +/- 7.5% baseline, P < 0.01, 1.0 mg. kg(-1)). LFP of SBP was also decreased (-46.3 +/- 10.9% baseline, P < 0.01, 1.0 mg. kg(-1)). Edrophonium may enhance (lower dose) or reduce (higher dose) cardiovascular autonomic drive in humans, as evidenced by the significant changes it evokes in HFP of the RRI (parasympathetic drive), and in the HFP and LFP of SBP (sympathetic drive). These observations may account for the modest autonomic side effects of edrophonium when this drug is used clinically.     

Halothane Suppression of Spinal Sensory Neuronal Responses to Noxious Peripheral Stimuli Is Mediated, in Part, by Both GABAA and Glycine Receptor Systems

Background: A major effect of general anesthesia is lack of response in the presence of a noxious stimulus. Anesthetic depression of spinal sensory neuronal responses to noxious stimuli is likely to contribute to that essential general anesthetic action. The authors tested the hypothesis that [gamma]-aminobutyric acid receptor type A (GABAA) and strychnine-sensitive glycine receptor systems mediate halothane depression of spinal sensory neuronal responses to noxious stimuli.

Methods: Extracellular activity of single spinal dorsal horn wide dynamic range (WDR) neurons was recorded in decerebrate, spinal cord transected rats. Neuronal responses to noxious (thermal and mechanical) and nonnoxious stimuli were examined in the drug-free state. Subsequently, cumulative doses (0.1-2.0 mg/kg) of bicuculline (GABAA antagonist) or strychnine (glycine antagonist) were administered intravenously in the absence or presence of 1 minimum alveolar concentration (MAC) of halothane.

Results: Halothane, 1.1%, depressed the response of WDR neurons to both forms of noxious stimuli. Antagonists, by themselves, had no effect on noxiously evoked activity. However, bicuculline and strychnine (maximum cumulative dose, 2.0 mg/kg) partially but significantly reversed the halothane depression of noxiously evoked activity. Similar results were seen with most, but not all, forms of nonnoxiously evoked activity. In the absence of halothane, strychnine significantly increased neuronal responses to low threshold receptive field brushing.     

Effectiveness of electroconvulsive therapy in community settings.

BACKGROUND: Clinical trials indicate that electroconvulsive therapy (ECT) is the most effective treatment for major depression, but its effectiveness in community settings has not been examined. METHODS: In a prospective, naturalistic study involving 347 patients at seven hospitals, clinical outcomes immediately after ECT and over a 24-week follow-up period were examined in relation to patient characteristics and treatment variables. RESULTS: The sites differed markedly in patient features and ECT administration but did not differ in clinical outcomes. In contrast to the 70%-90% remission rates expected with ECT, remission rates, depending on criteria, were 30.3%-46.7%. Longer episode duration, comorbid personality disorder, and schizoaffective disorder were associated with poorer outcome. Among remitters, the relapse rate during follow-up was 64.3%. Relapse was more frequent in patients with psychotic depression or comorbid Axis I or Axis II disorders. Only 23.4% of ECT nonremitters had sustained remission during follow-up. CONCLUSIONS: The remission rate with ECT in community settings is substantially less than that in clinical trials. Providers frequently end the ECT course with the view that patients have benefited fully, yet formal assessment shows significant residual symptoms. Patients who do not remit with ECT have a poor prognosis; this underscores the need to achieve maximal improvement with this modality.     

Microtubule-associated protein tau is required for axonal neurite elaboration by neuroblastoma cells.

NB2a/d1 neuroblastoma cells constitutively express multiple isoforms of the microtubule-associated protein tau and incorporate this protein into the axonal neurites elaborated during serum deprivation. To examine whether or not tau played an essential role in axonal outgrowth, cells cultured in serum-free medium were treated at 24 h intervals with antisense- and sense-oriented cDNA oligonucleotides (25 or 36 mers that span or are upstream of tau initiation codon) and were simultaneously serum deprived. Oligonucleotide uptake was confirmed by determination of intracellular levels of radiolabeled oligonucleotides. Treatment for 48 h with tau antisense oligonucleotides reversibly inhibited the expression of tau and the number of neurite-bearing cells compared with treatment with sense oligonucleotides. By contrast, tubulin expression was not affected. When cells were treated with antisense oligonucleotide simultaneously with serum deprivation, the initial outgrowth of neurites was unaffected, but continued neurite elongation was prevented. By contrast, neurite outgrowth at 4 h was inhibited when cells were pretreated with tau antisense 24 h before serum deprivation. Furthermore, intracellular delivery of anti-tau antiserum prevented neurite outgrowth and, in cells that had previously been deprived of serum for 24 h, induced retraction of existing neurites. These findings indicate that both the initiation and the continued outgrowth of neurites are dependent on tau and that pre-existing cytoplasmic pools of tau can mediate initial neuritogenesis.     

Challenges in geriatric oral health research methodology concerning caregivers of cognitively impaired elderly adults

Little is known about oral health care behaviors of community-dwelling, cognitively impaired elderly (CIE) persons. Few studies have been conducted regarding the actual provision of oral care for CIE persons or the attitudes and concerns about oral health among their caregivers. The CIE person's ability to perform self-care decreases over time, and the role of the caregiver in daily oral care becomes increasingly important. The purpose of this pilot study was to explore the attitudes toward oral health and identify related concerns among caregivers who care for community-dwelling CIE persons. Caregivers were surveyed by means of a self-administered, mailed questionnaire. To maintain confidentiality, an intermediary was used for recruitment and data collection. Overall, 148 caregivers were invited by an intermediary to participate in the survey; only 21 (14%) consented to participate and returned the questionnaire. This paper discusses some of the numerous methodological challenges identified when an attempt was made to survey caregivers' attitudes toward and barriers to providing oral care for a dependent CIE.     

Alexithymia in Holocaust Survivors with and Without PTSD

Alexithymia was measured in non-treatment seeking, community-dwelling Holocaust survivors using the Toronto Alexithymia Scale—Twenty Item Version (TAS-20). Scores of survivors with (n = 30) and without (n = 26) posttraumatic stress disorder (PTSD) were compared, and associations among alexithymia, severity of trauma, and severity of PTSD symptoms were determined. Survivors with PTSD had significantly higher scores on the TAS-20 compared to survivors without PTSD. TAS-20 scores were significantly associated with severity of PTSD symptoms, but not with severity of trauma. This study adds to our knowledge of the relationship between alexithymia and trauma by demonstrating that this characteristic is related to the presence of posttraumatic symptoms and not simply exposure to trauma.     

Acute Sinusitis in the Rabbit: A New Rhinogenic Model

The objective of this study was to create a rhinogenic model of sinusitis using an implanted foreign body in the nasal cavity of the rabbit. The study design was a prospective controlled trial of the experimental design. In this model an obstructing foreign body was placed into the nasal cavity and then impregnated with pathogenic bacteria. This model was studied histologically using wholemount techniques. Quantitative assessment of the degree of inflammation was made for the maxillary and ethmoid sinus and for overall effect for each animal. Bacteriologic study was performed in a limited number of animals. The results indicated that a significant infection develops in about half of animals. This peaks in intensity between 1 and 2 weeks after implantation and subsequently subsides with some evidence of long-term changes present after 4 weeks. It is concluded that this is a viable and perhaps preferable animal model to study sinusitis. Further investigation is necessary to completely characterize this model.     

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.