The involvement of the tetrodotoxin-resistant sodium channel Na(v)1.8 (PN3/SNS) in a rat model of visceral pain.

The present study investigated the effect of inhibiting the expression of Na(v)1.8 (PN3/SNS) sodium channels by an antisense oligodeoxynucleotide (ODN) on bladder nociceptive responses induced by intravesical acetic acid infusion in rats. Animals were injected intrathecally with either Na(v)1.8 antisense or mismatch ODN. Control cystometrograms under urethane anesthesia during intravesical saline infusion exhibited intercontraction intervals (ICIs) that were significantly longer in antisense-treated rats than in mismatch ODN-treated rats. Intravesical infusion of 0.1% acetic acid induced bladder hyperactivity as reflected by a 68% reduction in ICIs in mismatch ODN-treated rats but did not significantly reduce ICIs in antisense-treated rats. The number of Fos-positive cells after acetic acid administration were significantly reduced in the L6 spinal cord from antisense-treated animals, compared with mismatch ODN-treated animals. In addition, Na(v)1.8 immunoreactivity was reduced in L6 dorsal root ganglion neurons in the antisense-treated rat. In patch-clamp recordings, the conductance density of TTX-resistant sodium currents in dissociated bladder afferent neurons that were labeled by axonal transport of a fluorescent dye, Fast Blue, injected into the bladder wall was also smaller in antisense-treated rats than in mismatch ODN-treated rats, whereas no changes were observed in TTX-sensitive currents. These results indicate that the Na(v)1.8 TTX-resistant sodium channels are involved in the activation of afferent nerves after chemical irritation of the bladder. These channels represent a new target for the treatment of inflammatory pain from visceral organs such as the urinary bladder.

Hypotension, hypoxia, and head injury: frequency, duration, and consequences.

BACKGROUND: Retrospective studies have suggested an association between systemic hypotension and hypoxia and worsened outcome from traumatic brain injury. Little is known, however, about the frequency and duration of these potentially preventable causes of secondary brain injury. HYPOTHESIS: Early episodes of hypoxia and hypotension occurring during initial resuscitation will have a significant impact on outcome following traumatic brain injury. DESIGN: Prospective cohort study. SETTING: Urban level I trauma center. PATIENTS: Patients with a traumatic brain injury who had a Glasgow Coma Score of 12 or less within the first 24 hours of admission to the hospital and computed tomographic scan results demonstrating intracranial pathologic features. Patients who died in the emergency department were excluded from the study. MAIN OUTCOME MEASURES: Automated blood pressure and pulse oximetry readings were collected prospectively from the time of arrival through initial resuscitation. The number and duration of hypotensive (systolic blood pressure, < or =90 mm Hg) and hypoxic (oxygen saturation, < or =92%) events were analyzed for their association with mortality and neurological outcome. RESULTS: One hundred seven patients met the enrollment criteria (median Glasgow Coma Score, 7). Overall mortality was 43%. Twenty-six patients (24%) had hypotension while in the emergency department, with an average of 1.5 episodes per patient (mean duration, 9.1 minutes). Of these 26 patients with hypotension, 17 (65%) died (P =.01). When the number of hypotensive episodes increased from 1 to 2 or more, the odds ratio for death increased from 2.1 to 8.1. Forty-one patients (38%) had hypoxia, with an average of 2.1 episodes per patient (mean duration, 8.7 minutes). Of these 41 patients with hypoxia, 18 (44%) died (P =.68). CONCLUSIONS: Hypotension, but not hypoxia, occurring in the initial phase of resuscitation is significantly (P =.009) associated with increased mortality following brain injury, even when episodes are relatively short. These prospective data reinforce the need for early continuous monitoring and improved treatment of hypotension in brain-injured patients.

Educational needs of patients with advanced heart failure and their caregivers.

At the time of initial transplant evaluation, we evaluated the information and counseling needs of 82 outpatients with advanced heart failure and compared them with the needs of 74 of their caregivers. Both groups answered a 23-item questionnaire, which used a 5-point Likert scale to assess needs across 6 sub-scales specific to heart failure and the process of determining transplant eligibility. The 5 most important learning needs of patients and caregivers were similar, and we found significant differences only in the groups' responses to 3 individual questions. We conclude that nurses can meet the needs of patients and their caregivers by providing honest explanations, focusing on enhanced quality of life issues, and giving information for dealing with an emergency.

Down's syndrome, precocious puberty, and transverse vaginal septum: an unusual cause of abdominal pain.

Hematocolpos should be considered in adolescent girls who present with lower abdominal pain, a pelvic mass, and primary amenorrhea. The authors describe a rare case of a young child with Down's syndrome, precocious puberty, and hematocolpos caused by a transverse vaginal septum. The diagnosis was facilitated using a combination of computed tomography and ultrasound scanning. J Pediatr Surg 36:641-643.

Arm edema in breast cancer patients.

The improvement in the life expectancy of women with breast cancer raises important questions about how to improve the quality of life for women sustaining complications of breast cancer treatment. In particular, attention to common problems, such as arm edema, is of critical importance. We reviewed published breast cancer guidelines and literature identified via MEDLINE(R) searches in an effort to summarize the research literature pertinent to management of breast cancer-related arm edema, including incidence, prevalence, and timing; risk factors; morbidity; prevention; diagnosis; and efficacy of nonpharmacologic and pharmacologic interventions. We found that arm edema is a common complication of breast cancer therapy that can result in substantial functional impairment and psychological morbidity. The risk of arm edema increases when axillary dissection and axillary radiation therapy are used. Recommendations for preventive measures, such as avoidance of trauma, are available, but these measures have not been well studied. Nonpharmacologic treatments, such as massage and exercise, have been shown to be effective therapies for lymphedema, but the effect of pharmacologic interventions remains uncertain. Comparing results across studies is complicated by the fact that the definitions of interventions and measures of outcomes and risk stratification vary substantially among studies. As arm edema becomes more prevalent with the increasing survival of breast cancer patients, further research is needed to evaluate the efficacy of preventive strategies and therapeutic interventions.

Cerebral oxygenation during hemorrhagic shock: perils of hyperventilation and the therapeutic potential of hypoventilation.

OBJECTIVES: Prophylactic hyperventilation of patients with head injuries worsens outcome, presumably by exacerbating tissue hypoxia. Oxygen tension in brain tissue (PbrO2) provides a direct measurement of cerebral metabolic substrate delivery and varies with changing end-tidal carbon dioxide tension (ETCO2) and mean arterial pressure. However, the effects of hyperventilation and hypoventilation on PbrO2 during hemorrhagic shock are not known. The aim of this study was to examine the effects of alteration in ventilation on PbrO2 in hemorrhaged swine. METHODS: Clark-type polarographic probes were inserted into the brain tissue of seven swine to measure PbrO2 directly. To examine the effects of alterations in ventilation on hemorrhage-induced hypotension, swine were hemorrhaged to 50% estimated blood volume and PbrO2 was monitored during hyperventilation (RR = 30) and hypoventilation (RR = 4). RESULTS: After the 50% hemorrhage, PbrO2 declined rapidly from 39.8 +/- 4.6 mm Hg to 11.4 +/- 2.2 mm Hg. Hyperventilation resulted in a further 56% mean decrease in PbrO2. Hypoventilation produced a 166% mean increase in PbrO2. These changes were significant (p = 0.001) for absolute and percentage differences from baseline. CONCLUSION: During hemorrhage, alterations in ventilation significantly changed PbrO2: hyperventilation increased brain-tissue hypoxia whereas hypoventilation alleviated it. This finding suggests that hyperventilation has deleterious effects on brain oxygenation in patients with hemorrhagic shock and those with head trauma. Conversely, hypoventilation with resultant hypercapnia may actually help resolve hemorrhagic shock-induced cerebral hypoxia.

Increased c-fos expression in spinal lumbosacral projection neurons and preganglionic neurons after irritation of the lower urinary tract in the rat.

Chemical irritation of the lower urinary tract (LUT) induces c-fos expression in neurons in the lumbosacral (L(6) and S(1)) spinal cord. This study used axonal tracing with fluorescent dyes to identify the types of spinal neurons expressing Fos immunoreactivity (IR) after LUT irritation in the rat. Fos-IR was detected in lateral and medial superficial dorsal horn, the sacral parasympathetic nucleus (SPN) and lamina X around the central canal. Fos-IR was detected in spinal neurons projecting to supraspinal sites (brainstem and hypothalamus), in preganglionic neurons (PGN) and in unlabeled segmental interneurons. A substantial percentage (20%) of dye labeled PGN exhibited Fos-IR after LUT irritation; and a larger percentage (36%) exhibited Fos-IR after electrical stimulation of the pelvic nerve which contains afferent pathways from all of the pelvic organs. The majority (average 55%) of Fos-positive neurons projecting to supraspinal sites were also located in the region of the SPN. A selective distribution of different types of neurons was detected in this region: PGN were located ventral to the spinal projection neurons which in turn were located ventral to the majority of unidentified Fos-positive neurons. The distribution of Fos-positive PGN and projection neurons was similar in spinal intact and spinal transected animals indicating that c-fos expression was mediated by monosynaptic afferent input or input from segmental interneurons and was not due to activation of supraspinal micturition reflex pathways.

Effects of injectate volume on thermodilution measurements of cardiac output in patients with low ventricular ejection fraction.

OBJECTIVE: To determine the effect of 5-mL injectate on cardiac output measurements in critically ill patients with low ventricular ejection fraction (< 35%). METHODS: Thermodilution cardiac output measurements obtained with three 5-mL and three 10-mL (randomly ordered) iced injectates in 50 patients with low ejection fraction were averaged if the measurements were within 10% of the median. If the 3 measurements were not within those limits, additional measurements were obtained. RESULTS: Cardiac output measured with the 5-mL injectate (mean, 4.63 L/min) and cardiac output measured with the 10-mL injectate (mean, 4.52 L/min) were not significantly different (P = .64). Lower and upper limits of agreement were -1.7 L/min to +1.6 L/min. The bias (mean difference between 10- and 5-mL measurements) of all measurements was -0.09, and the precision was 1.43 L/min, with a 95% confidence limit (mean difference +/- 2 SD) of -1.7 to +1.6 L/min. An additional measurement was necessary in 77% of patients in the 5-mL group but in only 48% of the 10-mL group (P = .006). CONCLUSIONS: Cardiac outputs measured with 5- and 10-mL injectates do not differ significantly. The greater variability of measurements obtained with a 5-mL injectate suggests that more measurements, and thus more time, are needed to measure cardiac output accurately. Clinicians must weigh the benefit of minimizing fluid volume used against the potential decreased reliability of cardiac output measurements.

Transneuronal labeling of neurons in the adult rat brainstem and spinal cord after injection of pseudorabies virus into the urethra.

Transneuronal tracing techniques were used to identify sites in the central nervous system involved in the neural control of urethral function. The distribution of virus-infected neurons was examined in the spinal cord and brainstem at various intervals (56-96 hours) following pseudorabies virus (PRV) injection into the urethra. In the lumbosacral (L6-S1) spinal cord at 56 hours, neurons containing PRV immunoreactivity (PRV-IR) were located in the region of the sacral parasympathetic nucleus (SPN), around the central canal, and in the dorsal commissure. Some animals also exhibited PRV-IR in cells in the L6 dorsolateral motor nucleus. At longer survival times (72-96 hours), PRV-IR cells were observed in the superficial and deeper laminae of the dorsal horn, and increased numbers of PRV-IR cells were consistently detected in the region of the SPN, around the central canal, and in the dorsal commissure. PRV-IR fiber-like staining also occurred along the lateral edge of the dorsal horn extending from Lissauer's tract to the region of the SPN. In rostral lumbar segments (L1-L2), PRV-IR cells were located in the region of the dorsal commissure and the intermediolateral cell nucleus (IML), around the central canal, and in the dorsal horn. After 72-84 hours, PRV-IR cells were also noted at more rostral levels of the neuraxis including the medulla, pons, midbrain, and diencephalon. At 72 hours, PRV-IR cells were consistently observed in Barrington's nucleus (pontine micturition center), nucleus raphe magnus (RMg), parapyramidal reticular formation, and the A5 and A7 regions. At 78-84 hours, additional regions exhibited PRV-IR cells, including the periaqueductal gray, locus coeruleus, the dorsal and ventral subcoeruleus alpha, and the red nucleus. A few cells were also located in the lateral hypothalamic area. This distribution of PRV-labeled cells in the spinal cord and brainstem is similar in many respects to the distribution of cells labeled in previous studies by PRV injection into the urinary bladder. This overlap of urethra and bladder neurons is consistent with the results of physiological experiments indicating a close coordination between the central nervous control of bladder and urethral activity.

Localization of NADPH diaphorase in the lumbosacral spinal cord and dorsal root ganglia of the cat.

The distribution of NADPH-d activity in the spinal cord and dorsal root ganglia of the cat was studied to evaluate the role of nitric oxide in lumbosacral afferent and spinal autonomic pathways. At all levels of the spinal cord NADPH-d staining was present in neurons and fibers in the superficial dorsal horn and in neurons around the central canal and in the dorsal commissure. In addition, the sympathetic autonomic nucleus in the rostral lumbar segments exhibited prominent NADPH-d cellular staining whereas the parasympathetic nucleus in the sacral segments was not well stained. The most prominent NADPH-d activity in the sacral segments occurred in fibers extending from Lissauer's tract through laminae I along the lateral edge of the dorsal horn to lamina V and the region of the sacral parasympathetic nucleus. These fibers were very similar to VIP-containing and pelvic nerve afferent projections in the same region. They were prominent in the S1-S3 segments but not in adjacent segments (L6-L7 and Cx1) or in thoracolumbar and cervical segments. NADPH-d activity and VIP immunoreactivity in Lissauer's tract and the lateral dorsal horn were eliminated or greatly reduced after dorsal-ventral rhizotomy (S1-S3), indicating the fibers represent primary afferent projections. A population of small diameter afferent neurons in the L7-S2 dorsal root ganglia were intensely stained for NADPH-d. The functional significance of the NADPH-d histochemical stain remains to be determined; however, if NADPH-d is nitric oxide synthase then this would suggest that nitric oxide may function as a transmitter in thoracolumbar sympathetic preganglionic efferent pathways and in sacral parasympathetic afferent pathways in the cat.

Erythroid burst forming units (BFUE) grown from canine marrow and peripheral blood.

Studies of canine erythropoiesis in vitro have been limited to a relatively mature class of precursor that gives rise to erythroid colonies of 8-64 cells after 2-4 days in culture. In this report we provide data indicating that a second class of erythroid precursor that gives rise to clusters of colonies or bursts can be grown from both dog marrow and peripheral blood. Dog bursts reach maximum size after 7-14 days in culture and have an appearance characteristic of human erythroid bursts. Dog burst forming units, or BFUE, are low density cells (less than or equal to 1.065 g/ml) that can be separated from the majority of colony forming units, or CFUE, by density centrifugation.