Inhibition of the A-type K+ channels of dorsal root ganglion neurons by the long-duration anesthetic butamben.

n-Butyl-p-aminobenzoate (BAB; butamben) is a long-duration anesthetic used for the treatment of chronic pain. Epidural administration of BAB is thought to reduce the electrical excitability of dorsal root nociceptor fibers by inhibiting voltage-gated ion channels. To further investigate this mechanism, we examined the effects of BAB on the potassium currents of acutely dissociated neurons from the rat dorsal root ganglion (DRG). These neurons express a rapidly inactivating A-type K(+) current (I(A)) that is resistant to tetraethylammonium (20 mM) but inhibited by 4-aminopyridine (5 mM). At low concentrations, BAB (< or =1 microM) selectively inhibited the I(A) component of DRG K(+) current. The voltage dependence of activation and inactivation, kinetics of recovery from inactivation, and the pharmacology of the DRG I(A) were similar to those of the Kv4 family of K(+) channels. Reverse transcription-polymerase chain reaction was used to establish that the messages encoding for all three of the mammalian Kv4 channel subunits (Kv4.1-Kv4.3) were present in the rat DRG. BAB produced a high-affinity, partial inhibition of heterologously expressed Kv4.2 channels (K(D) = 59 nM) but did not alter the kinetics or voltage sensitivity of gating. Substituting polar threonines for conserved hydrophobic residues of the S6 segment weakened BAB binding but did not alter the voltage-dependent gating of the Kv4.2 channel. At physiological pH, BAB is uncharged, suggesting that hydrophobic interactions may contribute to drug binding. The data support a mechanism in which BAB binds near the narrow cytoplasmic entrance of Kv4 channels and inhibits current by a pore blocking mechanism.

[Collective responsibility of nurses in their involvement in their professional organizations]. / Responsabilidade coletiva na participação da enfermagem em suas entidades organizativas.

This study has as its objective the discussion of the nursing professionals' responsibility regarding their participation in professional associations, such as the Brazilian Association of Nursing (ABEn), the Regional Board of Nursing and the Nursing Union. The investigation was carried out with nurses from a private and a public educational institution and also from a private institution of assistance. As a result, it was verified that the participation of nurses in the organizations mentioned above is still scarce, but there is already some awareness of the need for integrating them.

Aging-associated down-regulation of ClC-1 expression in skeletal muscle: phenotypic-independent relation to the decrease of chloride conductance.

In order to clarify the mechanism underlying the reduction of resting membrane chloride conductance (gCl) during aging, the levels of mRNA encoding the principal skeletal muscle chloride channel, ClC-1, were measured. Total RNA samples isolated from tibialis anterior muscles of aged (24-29 months old) and adult (3-4 months old) rats were examined for ClC-1 expression using Northern blot analysis, and macroscopic gCl was recorded from extensor digitorum longus muscle fibers from each adult and aged rat in vitro using a two intracellular microelectrode technique. Although interindividual variability was observed, aged rats exhibited a parallel reduction of both gCl and ClC-1 mRNA expression as compared to adult rats. A linear correlation exists between individual values of ClC-1 mRNA and gCl. These results provide evidence that ClC-1 is the main determinant of sarcolemmal gCl and demonstrate that the decrease of gCl observed during aging is associated with a down-regulation of ClC-1 expression in muscle.

[The concept of quality of life in a group of nursing teachers--elements for reflection]. / A qualidade de vida na concepção de um grupo de professoras de enfermagem-elementos para reflexão.

It is a qualitative study, which was realized from the concept of quality of life, adopted by Meeberg (1993) and it is related to the opinion of a group of nursing teachers. It was observed that this concept is current in the speech of the people who were interviewed in a very clear way, especially in the attributes which are related to life itself and to an acceptable physical, mental, social and emotional state.

Hormonal changes throughout the menstrual cycle and increased anterior cruciate ligament laxity in females.

OBJECTIVE: To determine whether women experience significantly greater anterior cruciate ligament (ACL) laxity in conjunction with estrogen and progesterone surges during a normal 28- to 30-day menstrual cycle. DESIGN AND SETTING: Serial estrogen and progesterone levels were measured via radioimmunoassay procedures to identify the follicular and luteal phases of a subject's menstrual cycle and to determine periods of peak hormonal surges. Concomitant ACL laxity measures were taken using a knee arthrometer. Hormone levels and ACL laxity were assessed on days 1, 10, 11, 12, 13, 20, 21, 22, and 23 of the menstrual cycle. Day 1 corresponds to the menstrual phase, when estrogen and progesterone levels are at their lowest. Days 10 through 13 correspond to peak estrogen surge (follicular phase), and days 20 through 23 correspond to peak progesterone surge (luteal phase). SUBJECTS: Seven active females between the ages of 21 and 32 years with at least one apparently healthy knee (no known knee anomalies) volunteered for participation in this study. Each subject stated that she experienced a normal (28- to 30-day) menstrual cycle and was not currently taking any type of hormone therapy (eg, birth control medication). MEASUREMENTS: Blood was drawn on days 1, 10, 11, 12, 13, 20, 21, 22, and 23 of each subject's menstrual cycle, and ACL laxity measurements were assessed immediately after the blood draws. Estrogen and progesterone levels were determined via radioimmunoassay procedures, and ACL laxity was determined using a knee arthrometer. RESULTS: A within-subjects, repeated-measures analysis of variance was applied to determine the presence or absence of significant differences in ACL laxity values over the course of a subject's menstrual cycle. We found a significant difference in ACL laxity when comparing baseline levels of estrogen with peak levels of estrogen. A significant increase in ACL laxity was also noted when comparing baseline levels of progesterone with peak levels of progesterone. CONCLUSIONS: ACL laxity increased significantly throughout the menstrual cycle when comparing baseline with peak levels of estrogen and progesterone.

Pore-forming segments in voltage-gated chloride channels.

The ability to differentiate between ions is a property of ion channels that is crucial for their biological functions. However, the fundamental structural features that define anion selectivity and distinguish anion-permeable from cation-permeable channels are poorly understood. Voltage-gated chloride (Cl-) channels belonging to the ClC family are ubiquitous and have been predicted to play important roles in many diverse physiological and pathophysiological processes. We have identified regions of a human skeletal muscle ClC isoform that contribute to formation of its anion-selective conduction pathway. A core structural element (P1 region) of the ClC channel pore spans an accessibility barrier between the internal and external milieu, and contains an evolutionarily conserved sequence motif: GKxGPxxH. Neighbouring sequences in the third and fifth transmembrane segments also contribute to isoform-specific differences in anion selectivity. The conserved motif in the Cl- channel P1 region may constitute a 'signature' sequence for an anion-selective ion pore by analogy with the homologous GYG sequence that is essential for selectivity in voltage-gated potassium ion (K+) channel pores.

A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel.

Autosomal dominant myotonia congenita is an inherited disorder of skeletal muscle caused by mutations in a voltage-gated Cl- channel gene (CLCN1, 7q35). Here, we report that a mutation predicting the substitution of Gly 230 by glutamic acid (G230E) between segments D3 and D4 dramatically alters the pore properties of a recombinant human muscle Cl- channel (hCIC-1) expressed in a mammalian cell line (tsA201). The G230E mutation causes substantial changes in anion and cation selectivity as well as a fundamental change in rectification of the current-voltage relationship. Whereas wild-type channels are characterized by pronounced inward rectification and a Cl > thiocyanate > Br > NO(3) > I > CH(3)SO(3) selectivity, G230E exhibits outward rectification at positive potentials and a thiocyanate > NO(3) > I > Br > Cl > CH(3)SO(3) selectivity. Furthermore, the cation-to-anion permeability ratio of the mutant is much greater than that of the wild-type channel. Voltage-dependent blocks by intracellular and extracellular iodide help to distinguish two distinct ion binding sites within the hClC-1 conduction pathway. Both binding sites are preserved in the mutant but have decreased affinities for iodide. These findings suggest that Gly 230 is critical for normal ion conductance in hClC-1 and that this residue resides within the channel pore.

Molecular basis for decreased muscle chloride conductance in the myotonic goat.

Certain forms of myotonia, a condition characterized by delayed relaxation of muscle secondary to sarcolemmal hyperexcitability, are caused by diminished chloride conductance in the muscle cell membrane. We have investigated the molecular basis for decreased muscle chloride conductance in the myotonic goat, an historically important animal model for the elucidation of the role of chloride in muscle excitation. A single nucleotide change causing the substitution of proline for a conserved alanine residue in the carboxyl terminus of the goat muscle chloride channel (gCIC-1) was discovered. Heterologous expression of the mutation demonstrated a substantial (+47 mV) shift in the midpoint of steady-state activation of the channel, resulting in a diminished channel open probability at voltages near the resting membrane potential of skeletal muscle. These results provide a molecular basis for the decreased chloride conductance in myotonic muscle.

The stability of precision grip force in older adults.

The exceedingly large grip forces that many older adults employ when lifting objects with a precision pinch grip (Cole, 1991) may compensate for a reduced capability to produce a stable isometric force. That is, their grip force may fluctuate enough from moment to moment to yield grip forces that approach the force at which the object would slip from grasp. We examined the within-trial variability of isometric force in old (68-85 years, n = 13) and young (n = 11) human subjects (a) when they were asked to produce a constant pinch force at three target levels (0.49, 2.25, and 10.5 N) with external support of the arm, hand, and force transducer and (b) when they were asked to grasp, lift, and hold a small test object with a precision grip. Pinch force produced in the first task was equally stable across the two subject groups during analysis intervals that lasted 4 s. The elderly subjects produced grip forces when lifting objects that averaged twice as much as those produced by the young subjects. The force variability during the static (hold) phase of the lift for the old subjects was comparable with that used by the young subjects, after adjusting for the difference in grip force. The failure to observe less stable grip force in older adults contradicts a similar recent study. Differences in task (isometric grip force versus isometric abduction torque of a single digit) may account for this conflict, however. Thumb and finger forces for grip are produced through coactivation of many muscles and thus promote smooth force output through temporal summation of twitches. We conclude that peripheral reorganization of muscle in older adults does not yield increased instability of precision grip force and therefore does not contribute directly to increased grip forces in this population. However, force instability may affect other grip configurations (e.g., lateral pinch) or manipulation involving digit abduction or adduction forces.

The GORE-TEX anterior cruciate ligament prosthesis. A long-term followup.

The GORE-TEX anterior cruciate ligament prosthesis has been implanted in 268 patients at our institution since April of 1984. Follow-up for this study was available on 70% of these patients (188). Eighty-one percent (152) of these had the ligament for chronic injuries, 14% (26) for acute, and 5% (10) for subacute injuries. The patient population had an average age of 27.6 years (SD = 8.4) and a Tegner activity score of 6.05 (SD = 1.53). Prior procedures had been performed on 56% (105) of the patients. Concomitant procedures were performed in 73% (137) and included iliotibial band tenodesis, partial meniscectomy, posterior oblique ligament advancement, or meniscal repair. Followup averaged 48 months (range, 24 to 68). Evaluation included a questionnaire, physical examination, radiographs, KT-1000 arthrometer testing, and an activity score. Results were graded as excellent, good, fair, and poor. Acceptable results (good and excellent) were obtained in 83 patients (44%). Fifty-eight patients (32%) were rated excellent and 25 (13%) were rated good. Unacceptable results (fair and poor) were obtained in 105 patients (56%). Twenty-five patients (13%) were rated fair and 80 (42%) were rated poor. Subjective improvement was indicated by 166 patients (88%). Activity levels postoperatively as rated by the Tegner Scale improved in 2 (1%), remained the same in 167 (89%), and decreased in 19 patients (10%). Effusions occurred in 63 patients (34%) and caused an unacceptable result in 22 (12%). Rupture occurred in 23 patients (12%). Loosening greater than 3 mm occurred in 64 patients (34%) and led to unacceptable results in 37 (20%). Infection occurred in 5 patients (2.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Anterior cruciate ligament reconstruction with autografts.

Arthroscopically assisted ACL reconstruction has undergone rapid development in recent years. Although achievement of stability has been well-documented in open ACL reconstructive procedures, improved results may be obtained by reducing operative morbidity. Arthroscopically assisted ACL reconstruction appears to offer significantly diminished morbidity and thus offers more predictable rehabilitation, at least initially, after surgery. Improvements in instrumentation continue to refine the precision of this technique. Proper graft selection is an important issue that is paramount to the evolution of ligament reconstruction surgery. Although the central third patellar tendon is presently the operation by which all new techniques must be compared, the use of nonautogenous grafts may complement arthroscopic reconstruction by allowing further reduction in surgical morbidity. In this article we have expanded on some of the advantages of arthroscopic ACL reconstruction, given an overview of arthroscopic techniques, and described the techniques we prefer.

Rehabilitation following knee surgery. Recommendations.

Satisfactory results following knee surgery can be obtained only through the combined efforts of the surgeon, patient and therapist. A rehabilitative plan is based upon consideration of the effects of disuse and immobility on musculoskeletal tissues, and knowledge of the healing requirements following injury and specific surgical procedures. A balance must be made between simultaneous demands for protection against undue stress to facilitate healing and the need for stress to retard atrophy of musculoskeletal tissue. A thorough review of these concepts forms the basis for a rational approach to rehabilitation after specific surgical procedures. The phasic approach to knee rehabilitation is based upon progression in a logical fashion through the chronology of immobility, range of motion, progressive weight bearing and strengthening exercises. The latter category can be subdivided into its own progression from isometrics, isotonics, functional exercises through isokinetics. The ultimate goal and final phase is a safe return to full activity. By integrating a thorough knowledge of the healing parameters of musculoskeletal tissues and the simultaneous coexisting needs for protection and controlled stress, specific rehabilitative programmes can then be designed for the most common surgical procedures including: anterior and posterior cruciate ligament reconstruction, meniscal repair and meniscectomy, lateral release and hyaline cartilage procedures.

Postsurgical care for arthroscopic surgery of the knee and shoulder.

The use of a consistent, organized, and individualized plan of postoperative care and rehabilitation has aided us in helping our patients achieve an early return to function while minimizing cost and time off work or sport. An integral part of this plan is a home program of therapy outlined by a physical therapist after surgery, but carried out largely by the patient with simple affordable home equipment or easily accessible gymnasium equipment. Well-motivated patients will make optimal use of time and effort in achieving their own goals of return to function with appropriate guidance.

Patient tolerance to intravenous potassium chloride with and without lidocaine.

Hypokalemia is a common electrolyte abnormality. Intravenous repletion therapy with potassium chloride (KCl) in concentrations greater than 80-100 mEq/L is not recommended due to patient intolerance. Since this guideline at times may be clinically impractical, this study was designed to examine use of peripheral vein infusions of high concentration KCl therapy. Tolerance to KCl 20 mEq/65 ml iv with and without lidocaine 50 mg was evaluated in 18 hypokalemic subjects in a randomized, placebo-controlled, double-blind study. Subjective and objective assessments of adverse effects were determined throughout the infusion period. Pain was assessed by both verbal descriptor and visual analog scales and correlated significantly following infusion of KCl with or without lidocaine. Multivariant analysis demonstrated differences in pain perception between solutions, with significantly less pain following KCl with lidocaine versus KCl infusions. Transient adverse effects occurred in both groups, but the incidence was not statistically different. Use of concentrated iv KCl infusions may benefit hypokalemic patients with hypervolemia and/or severe potassium deficits. Addition of lidocaine clearly improves patient tolerance to intravenous KCl replacement.

Evaluation of therapeutic drug monitoring in a long-term care facility: a pilot project.

The need for a therapeutic drug monitoring service was evaluated in a 150-bed long-term care facility. Thirty blood samples from 28 residents (mean age 87.9 years) were assayed to determine trough drug concentrations. All subjects were examined to determine pharmacodynamic effect. Pharmacokinetic consultations were written for serum drug concentrations outside accepted ranges. Fifty percent (15 of 30) of serum drug levels measured were subtherapeutic; the remaining levels were in the normal therapeutic range. Based on this sample data, it could be concluded that a minimum of 32 percent and as many as 68 percent of serum drug levels would be subtherapeutic following drug analysis in similar nursing home populations. Of 12 consultations, recommendations for seven (58 percent) were accepted by the subject's primary care physicians. Four of the consultations (33 percent) resulted in dosage modifications. These results support the need for further study.

Human infection with herpes zoster: etiology, pathophysiology, diagnosis, clinical course, and treatment.

Herpes zoster is a cutaneous vesicular eruption resulting from recrudescence of the chickenpox virus. It is mainly a disease of adults, with a predisposition for the elderly or immunocompromised. Although usually localized, the disease can disseminate to visceral organs. Diagnosis is often made based on the characteristic pattern of the lesion and clinical features. Tzanck smear, viral isolation, seroconversion, antibody titers, and monoclonal antibodies may further aid or confirm the diagnosis. Clinical features of herpes zoster may follow a progression through 3 stages, prodromal, acute, and chronic. The prodromal and acute phases seldom require more than symptomatic management. The chronic pain syndrome, postherpetic neuralgia (PHN), demands a more aggressive approach. Pharmacologic intervention, neuroaugmentation, and/or surgery may prevent or alleviate PHN, but universal response to any of these therapeutic approaches is unlikely. Tricyclic antidepressants remain the first choice in treating this pain syndrome. A trial of antiviral therapy may be warranted in patients with disseminated disease or in immunocompromised patients with localized disease. Of the antiviral agents, acyclovir is considered the drug of choice by most clinicians.

Evaluation of creatinine clearance estimation in an elderly male population.

Thirty-one medically stable, elderly males (age 75 +/- 8.3 yrs) participated in a prospective study evaluating the accuracy of 16 methods of estimating creatinine clearance. Serum creatinine values were determined on the mornings of days 1, 4, and 5 to assure stable renal function. On the morning of day 3, a 24-hour urine collection was initiated. A statistically significant correlation existed between the measured and estimated clearance values for all 16 formulas. The correlation (r less than 0.65) was lower than that in previously published studies, however. Five of the formulas (1A, 5A, 5B, 7A, 7B) demonstrated no statistical difference between mean measured and estimated values. In this population, formula 2B was the least biased and formula 9B the most accurate. For all 16 methods, the bias was minimal and the relative accuracy of the estimated methods was comparable. The results support using methods to estimate creatinine clearance only as a rough bedside prediction of renal function in elderly males.

Continuous nasogastric morphine infusion.

Morphine sulfate is the narcotic analgesic most commonly used for pain treatment in terminally ill patients. This case report demonstrates a new method of morphine administration. A 56-year-old terminally ill cancer patient with severe pain from metastatic adenocarcinoma of the lung required continuous nasogastric feeding and around-the-clock narcotic analgesics. The patient was safely and effectively converted from a continuous intravenous morphine infusion to continuous nasogastric morphine-enteral feedings. This method of administration may benefit patients receiving continuous enteral tube feedings who either require high-dose morphine therapy or are unable to use the oral administration route.

Physeal bridge resection in infantile Blount disease.

Physeal bridge resection and osteotomy were used in the treatment of three cases of Stage VI Blount disease. At follow-up, all patients showed continued growth of the proximal tibial physis, as well as maintenance of alignment. Bridge resection with realignment osteotomy offers an attractive alternative in the treatment of skeletally immature patients with Blount disease and a medial physeal bridge.