Acquired pendular nystagmus: its characteristics, localising value and pathophysiology

Investigations were made of 16 patients with acquired pendular nystagmus and a further 32 cases reported in the literature were reviewed. Amongst our own patients two thirds had multiple sclerosis, almost one third a cerebrovascular accident or angioma and two had optic atrophy with squint. The nystagmus took forms which could be monocular or binocular, conjugate or disconjugate and could involve movements about single or multiple axes. Spectral analysis was used to characterise the amplitude and frequency of the movements and to estimate the degree of relationship (coherence) between movements of the two eyes or between movements of one eye about several axes. The oscillations ranged in frequency from 2·5 Hz to 6 Hz, with typical amplitudes between 3° and 5°. In a given patient all oscillations, regardless of plane, were highly synchronised. Somatic tremors of the upper limb, face and palate associated with the nystagmus were often at similar frequencies to the eye movement. The other ocular signs common to all our patients were the presence of squint with failure of convergence. Most patients also had skew deviation or internuclear ophthalmoplegia or both. The major oculomotor systems, that is, saccades, pursuit, optokinetic and vestibulo-ocular reflexes could be intact. It is inferred that the mechanism responsible for the pendular nystagmus lies at a level which is close to the oculomotor nuclei so that it can have monocular effects but is not part of the primary motor pathways. It is possible that this mechanism normally subserves maintenance of conjugate movement and posture of the eyes. The periodicity of the nystagmus is likely to arise from instability in a certain type(s) of neurone, for the associated somatic tremors have similar characteristics and yet involve very different neuronal muscular circuitry. Prognosis for cessation of the nystagmus is poor. In five patients with multiple sclerosis it was suppressed by intravenous hyoscine with, however, unacceptable subsequent side effects.     

Breathing and swallowing dynamics across the adult lifespan

BACKGROUND: Aberrations in the physiologic components of normal oropharyngeal swallowing have been linked to aspiration events and to predisposition to aspiration pneumonia, a common, deadly disease in elderly persons. Studies have demonstrated a temporal, physiologic link between breathing and the principal physiologic swallowing components involved in airway protection during swallowing. We developed a normative model of integrated breathing and swallowing patterns using concomitant videofluoroscopic images and nasal respiratory airflow recordings. OBJECTIVES: To establish normative temporal and respiratory-phase pattern relationships between breathing and swallowing in adult human beings across the aging continuum; to relate any alterations in these patterns to swallowing abnormality, an aspiration event during swallowing, and predisposition to aspiration pneumonia; and to develop clinically practical evaluation methods for identifying breathing and swallowing discoordination. SETTING: Fluoroscopy suite in an acute care hospital. PARTICIPANTS: Eighty-two healthy adult volunteers gave informed consent. All eligible healthy volunteers were welcome and were screened for age, race, and sex for equal distribution of each. INTERVENTION: Respiratory-phase patterns and the onset and duration of 11 predetermined swallowing events and associated respiratory activities were studied. All participants' single-liquid barium swallow examinations were studied with simultaneous videofluoroscopy and respiratory recordings. MAIN OUTCOME MEASURES: Onset of each of the 11 predetermined breathing and swallowing events was digitally recorded and analyzed. The phases of breathing before and after swallowing were identified. The presence, depth, and response to airway penetration were recorded and related to respiratory pattern. RESULTS: Four respiratory-phase patterns were identified that changed with advanced age. The correlation analyses of the temporal breathing and swallowing events revealed a normal pattern of 4 clearly distinguishable functional units. Differences in apnea duration and apnea offset occurred with advanced age. CONCLUSION: This research provides evidence for clearly distinguishable patterns and functional groupings of breathing and swallowing events, a necessary first step toward determining whether abnormal breathing and swallowing patterns in patients with dysphagia are associated with health outcome.     

Chaotic tumors and 2 mistakes of molecular oncologists

The structure of DNA is wondrously appealing in its elegant simplicity combined with its captivating power. The power of DNA derives directly from, and solely from, the fact that it represents digital information. However, this delightful digital determinism does not carry over into the multitude of cellular processes, especially in a cancer cell. This means that the sequencing of the human genome has some limitations regarding furthering the understanding of details of cancer cell biochemistry. The fading of digital control in cells, however, seems not well comprehended by most. This factor, together with the loss of DNA stability that is an underpinning of cancer, virtually guarantees that chaotic dynamics are very important in cancer cells. Yet, chaos is very underappreciated in oncology. Failure to appreciate the significance of the dissolution of digital control in cell dynamics and the lack of perception of the importance of chaotic dynamics in the cancer cell are 2 errors that will tend to enhance the frequency of mistakes made in analyzing information from gene expression microarrays, proteomic microarrays, and other advances in molecular oncology. This article explains how these mistakes will come about and why, in some instances, they could result in adverse effects in patient therapy as the goals for targeted, individualized, and molecular-based treatments are sought.     

Management of the chronically ventilated patient with a tracheostomy

Tracheostomy is the most common surgical procedure performed on critically ill patients. For those who survive their critical illnesses but remain ventilator-dependent, tracheostomy provides patients with a secure airway that frees the mouth for oral nutrition, enhances verbalized speech, and promotes generalized comfort. Avoiding complications from tracheostomy requires a skilled multi-disciplinary approach to ensure that the benefits outweigh the risks of the procedure.     

Multilevel and continuous pleural fluid pH likelihood ratios for draining parapneumonic effusions

BACKGROUND: Although clinical practice guidelines endorse the use of pleural fluid pH to select patients with parapneumonic effusions for pleural drainage, no studies have reported likelihood ratios for pleural fluid pH. OBJECTIVES: We derived and tested the value of continuous likelihood ratios for selecting pneumonia patients for pleural drainage. METHODS: Patient level pleural fluid pH results were obtained from a registry of primary studies that assessed the discriminative properties of pH. Multilevel likelihood ratios were calculated for four pH intervals. Continuous likelihood ratios were derived from logistic regression using discrete pH values. Binary, multilevel and continuous likelihood ratios were compared to evaluate the statistical (chi2) and clinical advantages of continuous likelihood ratios. RESULTS: Hundred and ninety-seven pleural fluid pH results were retrieved from published reports and categorized into four pH ordinal intervals. Multilevel likelihood ratios ranged from a low of 0.13 (95% CI, 0.04-0.41) for pH values >7.40 to a high of 15.80 (95% CI, 7.04-35.45) for pH values < or =7.00. Logistic regression derived the following equation for continuous likelihood ratios: exp[-7.168(measured pH - 7.207)]. Continuous likelihood ratios offered more diagnostic information both statistically (p < 0.005) and clinically compared with binary and multilevel likelihood ratios. CONCLUSIONS: Analysis of a patient registry allows the derivation of an exponential equation that calculates continuous likelihood ratios for discrete pleural fluid pH values. Continuous likelihood ratios provide more clinically and statistically significant information compared with binary and multilevel likelihood ratios for calculating posttest probabilities of the need to drain parapneumonic effusions.     

Does a preemptive block of the great auricular nerve improve postoperative analgesia in children undergoing tympanomastoid surgery?

We performed a double-blinded randomized controlled trial to evaluate the efficacy of preemptive analgesia in children undergoing tympanomastoid surgery. Children were divided into two groups: group block-block (BB) received a preemptive great auricular nerve block (GAN-block) with 0.25% bupivacaine with 1:200,000 epinephrine before incision followed by a second GAN-block with 0.25% bupivacaine with 1:200,000 epinephrine 1 h before the end of the procedure. Group sham block-block (SB-B) received a preemptive GAN-block with normal saline before surgical incision followed by a GAN-block with 0.25% bupivacaine with 1:200000 epinephrine 1 h before the completion of the procedure. All patients were evaluated for pain with the objective pain score (OPS) by a blinded observer. There was no difference in pain rescue requirements in the postanesthesia care unit (BB versus SB-B, 1 of 20 versus 3 of 20, P= 0.60) or in the short-stay unit (BB versus SB-B, 5 of 20 versus 11 of 20, P = 0.107) or for the entire hospital stay (P = 0.20). There was no significant difference between groups in the time to first rescue pain medication (BB versus SB-B, 226 +/- 71 min versus 201 +/- 94 min). There was no significant difference between groups regarding vomiting in the postoperative period (P = 0.52). We conclude that a preoperative GAN-block does not offer significant advantages for postoperative pain relief in children undergoing tympanomastoid surgery. IMPLICATIONS: This double-blinded randomized controlled trial compared the efficacy of preemptive analgesia with a peripheral nerve block of the great auricular nerve for decreasing postoperative pain in children undergoing tympanomastoid surgery. Preemptive analgesia did not improve the quality or duration of postoperative analgesia in our cohort.     

Benign postoperative spindle cell nodule of the urinary bladder? don't think so

According to colleagues specializing in genitourinary pathology, the so-called postoperative spindle cell nodule of the bladder can be extremely difficult to distinguish from a spindle cell sarcomatoid carcinoma. What I have learned in 25 years about spindle cell sarcomatoid carcinoma of the larynx may, by analogy, possibly help with the genitourinary pathology problem.     

The validity of subjective measures of body image disturbance

OBJECTIVE: We examined weight dissatisfaction (actual weight minus self-stated ideal weight) and weight goal (normative weight minus self-stated ideal weight) subjective indices in a large clinical sample to determine how the indices discriminate between diagnostic categories and relate to other measures of body image disturbance. METHOD: Approximately 200 anorexic, bulimic, and eating disorder not otherwise specified (NOS) participants reported their self-stated ideal weight and completed the Mizes Anorectic Cognitions (MAC) Questionnaire, Eating Disorders Inventory (EDI), and Restraint Scale-Revised. RESULTS: Compared with bulimic and NOS participants, anorexics reported less weight dissatisfaction but had an ideal weight that is farthest from normative weight. The weight dissatisfaction measure correlates well with other measures of body image disturbance, and both measures show evidence of discriminant validity. DISCUSSION: These two measures highlight the substantial differences in the nature of body image disturbance between the eating disorder diagnostic groups. Theoretical, clinical, and practical implications are discussed.     

Tamoxifen and tamoxifen ethyl bromide induce apoptosis in acutely damaged mammary epithelial cells through modulation of AKT activity

Normal human mammary epithelial cells (HMECs), unlike estrogen receptor-positive (ER+) breast cancers, typically express low nuclear levels of ER (ER-'poor'). We previously demonstrated that 1.0 microM tamoxifen (Tam) induced apoptosis in ER-'poor' HMECs acutely transduced with human papillomavirus-16 E6 (HMEC-E6) through a rapid mitochondrial signaling pathway. Here, we show that plasma membrane-associated E2-binding sites initiate the rapid apoptotic effects of Tam in HMEC-E6 cells through modulation of AKT activity. At equimolar concentrations, Tam and tamoxifen ethyl bromide (QTam), a membrane impermeant analog of Tam, rapidly induced apoptosis in HMEC-E6 cells associated with an even more rapid decrease in phosphorylation of AKT at serine-473. Treatment of HMEC-E6 cells with 1.0 microM QTam resulted in a 50% decrease in mitochondrial transmembrane potential, sequential activation of caspase-9 and -3, and a 90% decrease in AKT Ser-473 phosphorylation. The effects of both Tam and QTam were blocked by expression of constitutively active AKT (myristoylated AKT or AKT-Thr308Asp/Ser473Asp). These data indicate that Tam and QTam induce apoptosis in HMEC-E6 cells through a plasma membrane-activated AKT-signaling pathway that results in (1) decreased AKT phosphorylation at Ser-473, (2) mitochondrial membrane depolarization, and (3) activated caspase-9 and -3.     

Behavioral audiograms of homozygous med(J) mutant mice with sodium channel deficiency and unaffected controls

Complete behavioral audiograms were determined for med(J) mice (F1 offspring of C57BL/6JxC3HeB/FeJ) and unaffected controls from the same F1 background. The med(J) mutation results in greatly reduced levels of Scn8a voltage-gated sodium channels, which causes abnormal conduction of action potentials throughout the nervous system and may account for the virtual absence of spontaneous bursting activity in the dorsal cochlear nucleus. The med(J) mice also have tremors, display dystonic postures, and drag their hind legs. The mice were tested using a conditioned suppression/avoidance procedure, with minor modifications of the apparatus made to accommodate the motor-impaired med(J) mice. Thresholds were repeatedly obtained up to the age of 50 weeks to determine if the animals developed a hearing loss with age. The results indicate that med(J) mice have normal thresholds, with the first signs of hearing loss (detectable at 80 kHz) appearing for both the med(J) and normal mice by 48 weeks. Neither the med(J) nor the normal mice could hear below 1 kHz, indicating that house mice fall into the group of mammals with poor low-frequency hearing. The results also demonstrate that the conditioned suppression/avoidance procedure is well suited for assessing hearing in severely impaired, as well as normal, mice and that it can provide for the rapid determination of thresholds necessary to follow changes in hearing that may occur as the result of age, disease, mutation, or drugs.