Nonlinear finite element analysis of anular lesions in the L4/5 intervertebral disc.

Degenerate intervertebral discs exhibit both material and structural changes. Structural defects (lesions) develop in the anulus fibrosus with age. While degeneration has been simulated in numerous previous studies, the effects of structural lesions on disc mechanics are not well known. In this study, a finite element model (FEM) of the L4/5 intervertebral disc was developed in order to study the effects of anular lesions and loss of hydrostatic pressure in the nucleus pulposus on the disc mechanics. Models were developed to simulate both healthy and degenerate discs. Degeneration was simulated with either rim, radial or circumferential anular lesions and by equating nucleus pressure to zero. The anulus fibrosus ground substance was represented as a nonlinear incompressible material using a second-order polynomial, hyperelastic strain energy equation. Hyperelastic material parameters were derived from experimentation on sheep discs. Endplates were assumed to be rigid, and annulus lamellae were assumed to be vertical in the unloaded state. Loading conditions corresponding to physiological ranges of rotational motion were applied to the models and peak rotation moments compared between models. Loss of nucleus pulposus pressure had a much greater effect on the disc mechanics than the presence of anular lesions. This indicated that the development of anular lesions alone (prior to degeneration of the nucleus) has minimal effect on disc mechanics, but that disc stiffness is significantly reduced by the loss of hydrostatic pressure in the nucleus. With the degeneration of the nucleus, the outer innervated anulus or surrounding osteo-ligamentous anatomy may therefore experience increased strains.

Biomechanical concepts and effects.

Superficial tissue ulceration can be caused by the effect of mechanical loads acting on localised areas of skin and subcutaneous tissues. Be they low sustained loads applied for long periods or higher loads intermittently applied, the importance of the time factor has been recognised clinically by doctors and nurses. The significance of the type of loading and its magnitude in the damage of tissue is, however, not well agreed. This is in part due to the fact that knowledge of the mechanical and physiological responses of tissues is limited and in part to an inability to measure the forces applied to the tissues. This presentation outlines current understanding of the mechanics of tissue response.

Alarm interventions for nocturnal enuresis in children.

BACKGROUND: Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15 to 20% of five year olds, and up to 2% of young adults. OBJECTIVES: To assess the effects of alarm interventions on nocturnal enuresis in children, and to compare alarms with other interventions. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised trials register (searched 22 November 2004) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised trials of alarm interventions for nocturnal enuresis in children were included, except those focused solely on daytime wetting. Comparison interventions included no treatment, simple and complex behavioural methods, desmopressin, tricyclics, and miscellaneous other methods. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data. MAIN RESULTS: Fifty five trials met the inclusion criteria, involving 3152 children of whom 2345 used an alarm. The quality of many trials was poor, and evidence for many comparisons was inadequate. Most alarms used audio methods. Compared to no treatment, about two thirds of children became dry during alarm use (RR for failure 0.38, 95% CI 0.33 to 0.45). Nearly half who persisted with alarm use remained dry after treatment finished, compared to almost none after no treatment (RR of failure or relapse 45/81 (55%) vs 80/81 (99%), RR 0.56, 95% CI 0.46 to 0.68). There was insufficient evidence to draw conclusions about different types of alarm, or about how alarms compare to other behavioural interventions. Relapse rates were lower when overlearning was added to alarm treatment (RR 1.92, 95% CI 1.27 to 2.92) or if dry bed training was used as well (RR 2.0, 95% CI 1.25 to 3.20). Penalties for wet beds appeared to be counter-productive. Alarms using electric shocks were unacceptable to children or their parents. Although desmopressin may have a more immediate effect, alarms appear more effective by the end of a course of treatment (RR 0.71, 95% CI 0.50 to 0.99) and there was limited evidence of greater long-term success (4/22 (18%) vs 16/24 (67%), RR 0.27, 95% CI 0.11 to 0.69). Evidence about the benefit of supplementing alarm treatment with desmopressin was conflicting. Alarms were better than tricyclics during treatment (RR 0.73, 95% CI 0.61 to 0.88) and afterwards (7/12 (58%) vs 12/12 (100%), RR 0.58, 95% CI 0.36 to 0.94). AUTHORS' CONCLUSIONS: Alarm interventions are an effective treatment for nocturnal bedwetting in children. Alarms appear more effective than desmopressin or tricyclics by the end of treatment, and subsequently. Overlearning (giving extra fluids at bedtime after successfully becoming dry using an alarm), dry bed training and avoiding penalties may further reduce the relapse rate. Better quality research comparing alarms with other treatments is needed, including follow-up to determine relapse rates.

Complementary and miscellaneous interventions for nocturnal enuresis in children.

BACKGROUND: Nocturnal enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15 to 20% of five year olds, and up to 2% of young adults. OBJECTIVES: To assess the effects of complementary interventions and others such as surgery or diet on nocturnal enuresis in children, and to compare them with other interventions. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Register (searched 22 November 2004), the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS) (January 1984 to June 2004) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised trials of complementary and other miscellaneous interventions for nocturnal enuresis in children were included except those focused solely on daytime wetting. Comparison interventions could include no treatment, placebo or sham treatment, alarms, simple behavioural treatment, desmopressin, imipramine and miscellaneous other drugs and interventions. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data. MAIN RESULTS: In 15 randomised controlled trials, 1389 children were studied, of whom 703 received a complementary intervention. The quality of the trials was poor: four trials were quasi-randomised, five showed differences at baseline and ten lacked follow up data. The outcome was better after hypnosis than imipramine in one trial (relative risk (RR) for failure or relapse after stopping treatment 0.42, 95% confidence interval (CI) 0.23 to 0.78). Psychotherapy appeared to be better in terms of fewer children failing or relapsing than both alarm (RR 0.28, 95% CI 0.09 to 0.85) and rewards (0.29, 95% 0.09 to 0.90) but this depended on data from only one trial. Acupuncture had better results than sham control acupuncture (RR for failure or relapse after stopping treatment 0.67, 95% CI 0.48 to 0.94) in a further trial. Active chiropractic adjustment had better results than sham adjustment (RR for failure or relapse after stopping treatment 0.74, 95% CI 0.60 to 0.91). However, each of these findings came from small single trials, and need to be verified in further trials. The findings for diet and faradization were unreliable, and there were no trials including homeopathy or surgery. AUTHORS' CONCLUSIONS: There was weak evidence to support the use of hypnosis, psychotherapy, acupuncture and chiropractic but it was provided in each case by single small trials, some of dubious methodological rigour. Robust randomised trials are required with efficacy, cost-effectiveness and adverse effects carefully monitored.

Intracellular calcium oscillations regulate ciliary beat frequency of airway epithelial cells.

The effect of ATP-induced Ca2+ oscillations on ciliary activity was examined in airway epithelial cells by simultaneously measuring the ciliary beat frequency (CBF) and the intracellular Ca2+ concentration ([Ca2+]i) near the base of the cilia. Exposure to extracellular ATP (ATPo) induces a rapid and large increase in both [Ca2+]i and CBF, followed by oscillations in [Ca2+]i and a sustained elevation in CBF. After each Ca2+ oscillation, the [Ca2+]i returned to near basal values. By contrast, the CBF remained elevated during these Ca2+ oscillations, although each Ca2+ oscillation induced small variations in CBF. During Ca2+ oscillations, increases in CBF closely followed the rising phase of increases in [Ca2+]i, but declines in CBF lagged behind declines in [Ca2+]i. Higher frequency Ca2+ oscillations reduced variations in CBF, producing a stable and sustained elevation in CBF. The maximal CBF was induced by Ca2+ oscillations and was 15% greater than the CBF induced by the substantially larger initial [Ca2+]i increase. These data demonstrate that the rate of CBF is not directly dependent on the absolute [Ca2+]i, but is dependent on the differential changes in [Ca2+]i and suggest that CBF in airway epithelial cells is regulated by frequency-modulated Ca2+ signaling.

The time-dependent mechanical properties of skin.

The mechanical properties of the skin were investigated by applying a torsional deformation to a circumscribed area. Results of the tests indicate that the skin is nonlinear and time dependent. The dynamic response shows that the phase angle is insensitive to frequency below 1 Hz; the peak torque amplitude increases slowly above 0.004 Hz. A self-consistent description is presented utilizing continuous relaxation spectra. The technique describes the stress relaxation data and predicts the form of the dynamic response.

Free radical involvement in hypertrophic scar formation.

Hypertrophic scarring following thermal injury has become a major problem in Hong Kong. There is evidence that immunological and biochemical changes are associated with thermal injury, including pyridinoline crosslinks which are present in large quantities in hypertrophic scar, but the primary cause of hypertrophic scar formation still remains to be established. It has been reported that free radicals are assosciated with the formation of pyridinoline. In this study, attempts have been made to elucidate the involvement of free radicals in hypertrophic scar formation after thermal injury by determining the concentrations of Complement, free iron and pyridinoline crosslinks in collagen fibres. The results showed that the Complement activation product, C3d, was increased in the first week (i.e., day 7) postburn, indicating an acute inflammatory response. Free radicals, reported to be associated with the formation of pyridinoline crosslinks, and free iron content, were also found to have higher concentration in hypertrophic scar than in normal skin. The data suggest the involvement of free radical in hypertrophic scar formation. The observed increase in serum C3d concentration in about the first week indicates an acute inflammatory response to thermal injury. Both C3d and free iron concentrations (in vitro) are found higher in hypertrophic scar than in normal skin may suggest their roles in the generation of free radicals.

Prospective pricing system for tertiary neonatal intensive care.

This study assessed the potential impact of the federal neonatal diagnosis-related group (DRG) pricing system upon reimbursement to a state neonatal intensive care program. Data for length of intensive care unit stay, procedures, hospital charges, and audited cost reports from the state of Florida's ten regional neonatal intensive care centers were analyzed for 8,492 neonates whose charges totaled $118 million. Mean lengths of stay in these tertiary care centers were substantially longer than those reported for the federal DRGs, which were based on community hospital data. If federal DRG-based reimbursement to hospitals were implemented in Florida's perinatal intensive care program, compensation would range from 9% to 56% of actual hospital care charges. Federal DRG price rates were not predictive of hospital charges. Only 16% of the total variation in hospital charges was explained by differences among federal DRG rates (R2 = .16). Analysis of data by major determinants of resource consumption provided groups more homogeneous with respect to hospital charges and, hence, cost. Therefore, we developed a prospective pricing system that used modifications of federal newborn DRG system. These modifications resulted in a threefold increase in R2 (.52). Our proposed system permits prediction of cost and reimbursement for infants by three criteria: birth weight, need for mechanical ventilation and/or major surgery, and survival status and length of survival for those who die.

Prospective pricing model for neonatologists and obstetricians in tertiary care centers.

According to the new federal diagnosis-related group (DRG) system, hospitals are reimbursed fixed sums based on discharge diagnoses, rather than variable sums that depend on specific goods and services consumed and number of days hospitalized. The government is now exploring DRGs as a potential mechanism for reimbursing physicians. In Florida, two DRG-type reimbursement systems were developed for neonatal and obstetrical hospitalizations in tertiary care settings, as departures from the federal DRG system. Called neonatal care groups (NCGs) and obstetrical care groups (OBCGs), both classification systems predicted hospital charges in these settings more accurately than did federal DRGs. The feasibility of a prospective pricing system for neonatologists and obstetricians based on NCGs and OBCGs was investigated. The data showed that neonatologists' charges had a high correlation with hospital charges (r = .90) and that increasing levels of intensity of care as defined by the NCGs were reflected by consistent increases in reimbursement to neonatologists. If the NCG system were to be applied, neonatologists would receive compensation equivalent to that which they currently earn according to the fee-for-service system. In contrast, obstetricians' charges bore almost no relationship to hospital charges. However, modest differences in obstetrician's charges did emerge as a reflection of number of complications, which are incorporated into the OBCG categories; this suggests that a reimbursement system based on hospital OBCG categories might be applied to obstetricians.

Response of femoral venous oxygen tension to graduated pressure stockings--possible relationship to deep vein thrombosis.

Venous oxygen tension (pO2) was measured in discrete samples of blood obtained through the femoral vein of cardiac catheterisation patients before, during and after application of sustained external graduated pressure in the form of compression stockings (T. E. D. Kendall). There was a significant reduction (p less than 0.05) of pO2 from the baseline value both 30 sec and one minute after the application of the pressure stockings. Thereafter, the pO2 rose to baseline values. Two minutes after the stockings were removed there was again a significant reduction (p less than 0.05) of pO2 from the baseline value. We suggest that the decrease in venous pO2 on application of external pressure may be a reflection of washing out of stagnant hypoxic blood from the venous valve pockets, which may be related to the formation of deep vein thrombosis (DVT).

Biocompatibility assessment: application of fluorescent probe response (FPR) technique.

An in vitro test procedure capable of discriminating effectively between intact and membrane-damaged cells has been developed. This procedure utilizes fluorescein diacetate and ethidium bromide as fluorescent probes. The properties of the probes and the collapse in the selective cytoplasmic membrane permeability barrier of the damaged cells ensure the principal feature of the test procedure, that functional cells fluoresce bright green, but membrane-damaged cells fluoresce bright red. Investigations with natural rubber, silicone and acrylic polymers confirmed the suitability of the procedure to distinguish between materials on the basis of cytotoxicity.

The preclinical evaluation of the water vapour transmission rate through burn wound dressings.

The control of evaporative water loss, following burn injury, is of major importance to the overall condition of the patient, whether this control is by natural eschar or by a dressing. It is therefore important to preclinically determine the water vapour transmission rate of these dressings, firstly to make comparisons between different materials and secondly to screen prototype materials, under controlled conditions. A preclinical (in vitro) technique is described and the results are given for several commercially available dressings which encompass foam, film and hydrogel material categories.

An in vitro assessment of wound dressing conformability.

An in vitro assessment technique has been developed to determine the conformability of wound dressings. The technique employed is based on an inflation technique which provides a measurement of the minimum radius of curvature which a specific dressing will adopt under pressure. A pressure of 40 mmHg was chosen as this had been shown to be the maximum tolerable pressure before the occurrence of tissue breakdown. This radius is then matched to the natural radii of the body surfaces and an assessment of conformability can be made. A series of commercially available dressings have been assessed with respect to their conformability, and to the enhancement of their conformability due to viscoelastic creep behaviour.

Principles of burn dressings.

Throughout history burn wounds have been treated by covering with dressings of many different materials. The successful application of a burn dressing remains an objective for biomaterial development. This paper examines how the burn wound differs from other skin injuries, the requirements of the ideal burn wound dressing, and reviews the type of dressings available. The dressings in common use in the treatment of burns are compared with the 'ideal' dressing, in so far as it can be defined.

A two-platform task reveals a deficit in the ability of rats to return to the start location in the water maze.

The ability of rats to return to the start location was examined with a 4-arm radial water maze. The task required rats to find 2 hidden platforms in sequence. Rats were released from 1 of 3 arms and there was a platform located in the fourth arm. Once a rat found this platform, a 2nd platform was raised in another location, which was either the start location, for 1 group, or another fixed location, for a control group. Across 3 experiments, all rats learned the location of the 1st fixed platform in 80 to 120 trials. However, rats had difficulty finding a 2nd platform if it was at the start location. Control groups revealed that rats could learn 2 platform locations and that the difficulty in learning to return to the start location did not seem to be attributable to its aversive nature. In separate groups, exposure to the start location was increased by starting the rats from an initially stable platform. Rats still did not readily learn to return to the start location. The authors suggest that start location, when varied, cannot readily be used to define the location of a hidden platform.

Propagation of intercellular calcium waves in C6 glioma cells transfected with connexins 43 or 32.

In this study, gap junction-deficient C6 glioma cells, transfected with either connexin 43 (Cx43) or 32 (Cx32), have been used to evaluate the ability of these connexins to pass intercellular Ca2+ waves. Ca2+ waves, observed with fluorescence imaging using fura-2 or fluo-3, were initiated by mechanical stimulation in the presence of a supra-perfusion of the extracellular fluid or by the non-contact technique of flash photolysis of intracellular caged-IP3. Following manual mechanical stimulation, the parental C6 glioma cells and cells expressing Cx43 and Cx32 gap junctions all propagated intercellular Ca2+ waves. Ca2+ waves in cells expressing Cx43 traveled approximately twice the distance as compared to waves in cells expressing Cx32 or parental cells. The cells expressing Cx43 were also about twice as sensitive to ATP as cells expressing Cx32. In the presence of a supra-perfusion of extracellular fluid, the Ca2+ waves in parental cells were almost abolished while the mechanically induced Ca2+ waves in the cells expressing Cx43 and Cx32 propagate similar but limited distances of several cells in a direction opposite to the fluid flow. The photolytic release of IP3, but not Ca2+, in cells expressing Cx43 or Cx32 resulted in the propagation of Ca2+ waves that traveled distances similar to those observed in the presence of supra-perfusion. Parental C6 glioma cells did not initiate intercellular Ca2+ waves when stimulated by photolysis. From these studies we conclude that (1) both Cx43 and Cx32 based gap junctions are permeable to IP3 and can serve to communicate Ca2+ waves, (2) that Ca2+ wave propagation via gap junctions was dependent on the diffusion of IP3 but not Ca2+, (3) that an extracellular messenger capable of communicating waves is released from only the stimulated cell, and (4) that simultaneous intracellular and extracellular signaling can occur to enhance the propagation of intercellular Ca2+ waves.

Use of ultrasound in monitoring ovulation induction with human pituitary gonadotropins.

Serial follicular growth was studied using real-time ultrasound scanning in 26 anovulatory patients in 55 cycles stimulated with exogenous human pituitary gonadotropin (hPG) and human chorionic gonadotropin (hCG). Dosage was monitored with urinary total estrogen estimations. The ultrasound findings were not made known to the attending physician. Forty-four cycles (80%) were ovulatory, and conception occurred in 13. The mean follicular diameter of 17 to 25 mm at ovulation corresponded with the range observed in spontaneous cycles, although the rate of follicular growth was faster with hPG. On the day the ovulatory dose of hCG was given, as determined by the first urinary estrogen value greater than 50 microgram/24 hours, estrogen excretion was similar whether single or multiple follicles of potential ovulatory size were present, but mean follicular diameters were significantly smaller when there was more than 1 follicle. During the last 4 days before ovulation, the mean diameters in conceptual cycles increased from 14.2 mm to 19.7 mm, values similar to those observed in spontaneous cycles, but different growth patterns occurred in some nonconceptual cycles. Ovarian hyperstimulation was identified by ultrasound scan in 4 of 5 cycles before urinary estrogen excretion exceeded the normal range. Although ultrasound scan does not supplant estrogen monitoring, it can assist in the early detection of hyperstimulation, in the more accurate timing of the ovulatory dose of hCG, and in the withholding of hCG when 3 or more ovulations are possible. It is recommended that ultrasound examination be performed in all patients before the ovulation-inducing dose of hCG is given to provide information on the number of follicles that are likely to ovulate and thus avoid conception of more than twins.

Treatment-independent pregnancies after cessation of gonadotropin ovulation induction in women with oligomenorrhea and anovulatory menses.

Life-table analysis was performed for the cumulative spontaneous pregnancy rate (CSPR) of 56 patients with oligomenorrhea and anovulatory cycles who had been treated with gonadotropin for ovulation induction between 1963 and 1985. Twenty-seven had at least one spontaneous pregnancy, giving rise to a CSPR of 66.4% (95% confidence limit [CL] 42.4% to 90.4%) at 115 months for the first spontaneous pregnancy, which is significantly lower than the cumulative induced pregnancy rate (CIPR) of 88.6% at 23 months for the first course of gonadotropin therapy (P less than 0.0001). This fertility potential was not affected by the baseline estrogen and follicle-stimulating hormone levels, diagnosis, result of gonadotropin therapy, and age and menstrual pattern during exposure to spontaneous pregnancy by Cox regression analysis. More multiple births occurred in the induced pregnancies than in the spontaneous pregnancies (P = 0.005).