Charges and lengths of stay for acute and inpatient rehabilitation treatment of traumatic brain injury 1990-1996.

This investigation evaluated yearly trends in charges and lengths of stay for patients with brain injury in acute care and rehabilitation settings over a 7 year period. Data was collected from 800 consecutive patients enrolled in four NIDRR Model Systems Traumatic Brain Injury programmes. Acute care daily charges showed almost routine increases, averaging nearly $550 per year. Conversely, lengths of stay generally showed a downward trend, with annual reductions averaging 2.25 days. Admission lengths of stay averaged 22-29 days between 1990-1994. Admissions averaged less than 20 days beginning in 1995, with the 1996 average of 16 days, nearly half that of the 1993 average. Between 1990-1996, average daily rehabilitation charges increased each year, with the rise averaging $83 or 7%. The rise in daily rehabilitation charges was offset by corresponding decreases in lengths of stay averaging 3.65 days or 8% annually. Increases in daily charges for brain injury rehabilitation care were roughly comparable to those for general medical care prices. However, the rate of change in acute care charges was substantially greater, with annual increases averaging 10% more than national medical care prices. The steady downward trend in lengths of stay raises serious concerns about the future availability of health care services to persons with brain injury.

Long-term recovery course after traumatic brain injury: a comparison of the functional independence measure and disability rating scale.

OBJECTIVES: To study group changes over time after traumatic brain injury (TBI). DESIGN: Prospective cohort. SETTING AND PARTICIPANTS: TBI Model System Database with 1160 subjects using cohort with complete data. MAIN OUTCOME MEASURES: Functional Independence Measure (FIM) and Disability Rating Scale (DRS) at rehabilitation discharge and annually after injury. RESULTS: Statistically significant differences existed between FIM-total, FIM-Motor, FIM-Cognitive subscales, and DRS at rehabilitation discharge and year 1. Comparisons of year-to-year intervals, years 1 and 3, 1 and 5, and 3 and 5, revealed no statistically significant differences except between years 1 and 3 and 1 and 5 with DRS, and years 1 and 5 with FIM. Including only those more dependent at year 1 revealed statistically significant differences between years 1 and 2 and 1 and 5 on FIM-Cognitive and DRS, but not the FIM-Motor. The proportion of change for FIM and DRS items from year 1 to years 2 and 5 revealed DRS Level of Functioning and Employability items accounted for most DRS change, whereas FIM change was more spread across its components. CONCLUSIONS: DRS is more sensitive to changes during a shorter time period than FIM and seems to be more appropriate for detecting long-term deficits. However, research studies aimed at detecting meaningful changes year to year after TBI may need to use other tools or consider changes among individuals instead of group changes. DRS Level of Function and Employability Items represent complex functions expected to recover later than the more basic DRS items. Sole use of these two DRS items might provide an efficient means of measuring long-term recovery when resources are limited, whereas expansion of these two items might allow greater sensitivity and detail.

Assessing traumatic brain injury outcome measures for long-term follow-up of community-based individuals.

OBJECTIVES: To determine which outcome measures are best and least suited for assessing long-term functional outcome of individuals with traumatic brain injury (TBI) in the community. DESIGN: Survey of participants in the community an average of 5 years after TBI. A battery of outcome measures was given. SETTING: Community in northern California after inpatient rehabilitation. PARTICIPANTS: Forty-eight adult individuals with prior moderate to severe TBI. All subjects had received inpatient rehabilitation 2 to 9 years previously and could be reached for telephone interview. MAIN OUTCOME MEASURES: The Community Integration Questionnaire, Neurobehavioral Functioning Inventory (NFI), Patient Competency Rating Scale (PCRS), Level of Cognitive Functioning Scale (LCFS), FIM instrument, Functional Assessment Measure (FIM+FAM), Supervision Rating Scale (SRS), Disability Rating Scale (DRS), Revised Craig Handicap Assessment and Reporting Technique (R-CHART), and Glasgow Outcome Scale (GOS). The number of maximal scores on each of the surveys was studied to determine which instruments continued to reveal deficits years after TBI. RESULTS: Most individuals obtained maximum scores, ie, functional independence, on these scales: LCFS, FIM motor subscale and total score, R-CHART physical independence subscale, FIM+FAM, GOS, and the SRS. Measures with the fewest maximum scores (<36%, measuring deficits still extant in the group) were the R-CHART cognition subscale and the NFI memory/attention and communication subscales, and employment subscales. Items, subscales, and total scores that showed good variability and correlated most highly and frequently with other scales also demonstrating good variability were the PCRS, the DRS and FIM+FAM employment items, the R-CHART cognition subscale, and the NFI motor, memory/attention, communication, and depression subscales (the R-CHART cognition subscale and NFI memory/attention subscale were highly correlated with the PCRS;.84,.83). CONCLUSIONS: Measures that appeared to contribute little to assessing functional status of a TBI sample years postinjury were the FIM, FIM+FAM, SRS, GOS, and LCFS. Measures that showed a range of deficits across participants were DRS employability, the NFI, PCRS, and the R-CHART cognition subscale.

The substrate for brain-stimulation reward in the lateral preoptic area. I. Anatomical mapping of its boundaries.

Given the putative role of the lateral preoptic area as a primary contributor of the cell bodies of origin of the descending pathway linking a subset of lateral hypothalamic and ventral tegmental area reward neurons, the distribution of self-stimulation sites in this structure was mapped in 22 animals using moveable electrodes and threshold procedures. Ninety-seven electrode sites were evaluated with placements ranging from just rostral to the midline convergence of the anterior commissure back to the transition zone between the lateral preoptic and lateral hypothalamic areas; of these, roughly 2/3 supported self-stimulation which was widely observed throughout the lateral preoptic area and medial forebrain bundle. In general, self-stimulation thresholds obtained from lateral sites were most stable, and progressively so approaching more caudal regions. Examination of the slopes of the period/current trade-off functions revealed a tendency for higher values in lateral and caudal sites; in contrast, dorsoventral excursions did not influence these estimates. Taken together, these data provide support for the notion that the substrate for brain-stimulation reward in the lateral preoptic area has a relatively homogeneous distribution that is more diffusely organized than that found in reward sites activated further caudally in the medial forebrain bundle.

The substrate for brain-stimulation reward in the lateral preoptic area. II. Connections to the ventral tegmental area.

This experiment investigated the existence of a direct anatomical connection between lateral preoptic and ventral tegmental areas that mediate brain stimulation reward using the behavioral adaptation of the collision test. This test is a double-pulse, two-electrode technique based on the axonal conduction failure that occurs when two separate sites in the same axon bundle are concurrently stimulated. This anatomical arrangement is inferred from the shape of the function relating the effectiveness of double-pulse stimulation to the interval between pulses. In this study, nine rats with a total of 44 pairs of sites were examined. In two pairs only was there a profile suggestive of an axonal collision effect, while the double-pulse effectiveness curve consistent with the properties of transynaptic collision was apparent for a single pair of sites; the remaining 93% were associated with relatively flat effectiveness curves. While electrode misalignment could be responsible for these results, there was adequate sampling to suggest that the preponderance of first stage signals that give rise to the rewarding effects mediated by the lateral preoptic and ventral tegmental areas do not travel along the same fiber bundle. However, stimulation applied to both sites concurrently produces a summation that is roughly 40% greater than stimulation at either site alone, suggesting reasonable integration of the reward signals generated by lateral preoptic and ventral tegmental area stimulation.

Functional magnetic stimulation facilitates gastrointestinal transit of liquids in rats.

The purpose of this study was to investigate the effect of a relatively novel technology, functional magnetic stimulation (FMS), on gastrointestinal transit of liquids in rats. Orogastric gavage with technetium-99 solution was used to assess gastric emptying and gastrointestinal transit time in 92 rats. FMS was performed over the anterior cervical and/or dorsal thoracolumbar regions using a figure-8 coil. Stimulation protocols were 1, 2, or 4 h in length. FMS accelerated gastric emptying and decreased gastrointestinal transit time. The acceleration was dependent on the stimulation parameters used as well as on the duration of the protocol; high levels of FMS produced a quicker effect, whereas lower levels were effective at later times. This study provides evidence that FMS could be an alternative or adjunct therapy to treat disorders in gastrointestinal motility.

The Center for Outcome Measurement in Brain Injury (COMBI): An Internet resource you should know about.

OBJECTIVE: This article describes the Center for Outcome Measurement in Brain Injury (COMBI), an Internet resource that provides information on brain injury outcome measures. Funded by the National Institute on Disability and Rehabilitation Research (NIDRR), the COMBI is a collaborative project of eight Traumatic Brain Injury (TBI) Model System centers. Information the COMBI provides includes rating scales and form(s) syllabus and administration guidelines, descriptions of properties, references in the literature, a frequently asked questions (FAQ) section, training and testing materials, and contact information. CONCLUSIONS: As a dissemination effort, the results of the COMBI project have been outstanding with over 1,500 users accessing information every month. The project has a truly international scope, with 20% of its users being outside the United States.

Open saphenectomy complications following lower extremity revascularization.

A review of saphenectomy site complications following lower extremity revascularization was conducted. Leg incisions used for 133 consecutive infrainguinal bypass procedures were categorized by location. Patient and procedural risk factors were analyzed for risk of wound complications. Procedure, limb and patient outcome were reported via life table analysis. Incisional wound complications followed 32/133 procedures (24%), including 15 groin, eight saphenectomy, five distal and four vein/distal incisions. There were five grade I and three grade II saphenectomy complications. Only weight (body mass index) predicted the likelihood of wound complication (P < 0.05). The 6-month primary patency rate was 79% (mean follow-up 22 months). Four-year assisted primary patency, limb salvage and survival rates were 75, 87 and 57%, respectively. Most bypass-related wound complications (24/32, 75%) involve arterial access incisions. Incisional complications are related to body mass index. Only 6% of GS vein bypass procedures develop saphenectomy site complications. Limiting saphenectomy size may not significantly reduce incisional morbidity following bypass grafting.

Expiratory muscle activation by functional magnetic stimulation of thoracic and lumbar spinal nerves.

OBJECTIVE: This study was conducted to stimulate respiratory muscles by functional magnetic stimulation (FMS) of the spinal nerves (T1-L5) to obtain maximum expiratory function. DESIGN: A prospective before and after trial. SETTING: Functional Magnetic Stimulation Laboratory, Spinal Cord Injury Service, VA Palo Alto Health Care System, Palo Alto, CA. PARTICIPANTS: Twelve normal able-bodied subjects. INTERVENTION: A commercially available magnetic stimulator with a round magnetic coil (MC) was used. Respiratory muscle activation was achieved by placing the MC at each spinous process ranging from T1 to L5 vertebral levels. MAIN OUTCOME MEASURE: The planned major outcome was to determine the optimal MC placement for producing maximal expiratory pressure (MEP) and expiratory reserve volume (ERV) by FMS. These measurements were compared with the subjects' voluntary maximal efforts. A profile with varying stimulation intensities was also obtained in select individuals for determining the highest expiratory pressure. RESULTS: Stimulation at the T9 spinal level resulted in the highest mean MEP and ERV. Stimulation between T8 and L5 produced similar MEP and ERV as obtained from the T9 MC placement. The mean maximum MEP and ERV produced by FMS were 76.8 +/- 6.4 cm H2O (7.52 +/- 0.62 kPa) and 1.28 +/- 0.15 L, which were 67% and 79% of the subjects' voluntary maximal efforts, respectively. A stimulation intensity of 80% resulted in the highest expiratory pressure. CONCLUSION: FMS of lower thoracic and lumbar regions produced significant expiratory pressures and volumes. FMS of the expiratory muscles may prove to be a valuable technique for restoring cough in patients with spinal cord injury or other neurologic diseases, and in critical care or perioperative settings.

Control of motor seizures by brotizolam with maintenance of stable refractory periods for self-stimulation.

In recent years, we have been pursuing our mapping investigations of the substrate for brain-stimulation reward in regions of the anterior hypothalamic and lateral preoptic areas. However, one problem is that stimulation of these sites often generates overt seizures so that their suppression via a pharmacological means would be very useful. The sedative-hypnotic benzodiazepine, brotizolam, is reportedly a long-lasting anticonvulsant. Hence, its effects on motor seizures elicited from stimulation of the lateral preoptic area were evaluated in the first experiment. Both tested doses (5.0 and 7.5 mg/kg) of the drug were shown to significantly decrease the number, and marginally, the severity of stimulation-induced seizures; furthermore, this effect was relatively long lasting, up to about 3 h. The higher dose of brotizolam did not alter the single-pulse thresholds for self-stimulation, a requirement for evaluations of poststimulation excitability, the purpose of the second experiment. Here, our interest was in documenting whether the membrane properties of the stimulated neurons, as assessed by refractory periods, were altered by brotizolam. No differences in the time course of recovery were observed; refractoriness began between 0.4 and 0.8 ms, and reached 50% recovery by 2.0 ms, which is consistent with the pattern of poststimulation excitability typically measured at these sites. Thus, in addition to its long-lasting suppression of motor seizures in rats, brotizolam does not alter the time course of recovery from refractoriness of the neurons that mediate brain-stimulation reward in the lateral preoptic area.

Influence of bombesin on threshold for feeding and reward in the rat.

Bombesin's purported role in satiety mechanisms prompted this investigation of its effects on thresholds for stimulation-induced feeding and self-stimulation in the rat. Single electrodes were implanted in the lateral hypothalamus and the ability of each electrode to support self-stimulation and stimulation-induced feeding was evaluated at four current levels between 80 and 320 microA. The frequency thresholds associated with each current value were assessed following four intraperitoneal doses of bombesin, 2, 4, 8, and 16 micrograms/kg, as well as a saline dose. Bombesin increased the thresholds for stimulation-induced feeding at doses known to reduce food intake without influencing self-stimulation thresholds. From these findings we conclude that (1) the effects of peripheral bombesin on stimulation-induced feeding are analogous to its effects on normal feeding and (2) the data provide additional evidence for a pharmacological dissociation between stimulation-induced feeding and reward.

Subcellular localization of rolipram-sensitive, cAMP-specific phosphodiesterases. Differential targeting and activation of the splicing variants derived from the PDE4D gene.

Biochemical and immunofluorescence analyses revealed that phosphodiesterase variants encoded by the PDE4D gene are targeted to discrete subcellular structures. In quiescent FRTL-5 thyroid cells, the rolipram-sensitive phosphodiesterase (PDE) activity (cAMP-PDE) was recovered both in the soluble and particulate fractions of the homogenate. Although an immunoreactive 93-kDa PDE (PDE4D3) variant was recovered in both compartments, a 105-kDa variant with the properties of PDE4D4 was recovered mostly in the particulate fraction. The PDE4D3 form was readily solubilized with nonionic detergents. Conversely, the PDE4D4 form required buffers containing ionic detergents for extraction, suggesting that different mechanisms target these variants to insoluble structures. A 15-min stimulation with thyroid-stimulating hormone (TSH) led to an activation of the cAMP-PDE in both compartments and was correlated with a shift in electrophoretic mobility of the PDE4D3 polypeptide. Long term incubation with TSH caused an increase of the PDE activity in the soluble fraction and the appearance of a 68-kDa immunoreactive polypeptide with the properties of PDE4D2. Immunofluorescence analysis showed, in addition to diffuse staining, a signal localized on regions adjacent to the plasma membrane on cytoskeletal structures and in a perinuclear region of quiescent cells. Long term incubation with TSH caused an increase in the immunofluorescence signal in the soluble compartment. These data demonstrate that three PDE4D splicing variants are targeted to discrete subcellular compartments and that hormones cause the activation of these isoforms in a temporally and spatially dependent manner.

Characterization of the rolipram-sensitive, cyclic AMP-specific phosphodiesterases: identification and differential expression of immunologically distinct forms in the rat brain.

To determine the properties of the cAMP-specific, rolipram-sensitive phosphodiesterases (cAMP-PDEs) that are expressed in different organs, monoclonal and polyclonal antibodies were raised against different epitopes present in the cAMP-PDE sequences. Of the several antibodies generated against peptides and fusion proteins, one monoclonal and four polyclonal antibodies recognized both the native cAMP-PDEs as well as the denatured proteins on Western immunoblot analysis. An immunoprecipitation assay demonstrated that these antibodies recognized the recombinant rat PDE4A, PDE4B, and PDE4D proteins with different avidity. The polyclonal antibody K118 and the monoclonal M3S1 were most specific for rat PDE4B and PDE4D forms, respectively, whereas the AC55 antiserum displayed the highest affinity for PDE4A forms. This selectivity was confirmed by Western blot analysis using recombinant rat PDE4A, PDE4B, and PDE4D proteins expressed in a heterologous system. These antibodies were used to characterize the cAMP-PDEs expressed in the rat brain. An immunoblot of extract of cortex and cerebellum demonstrated that at least seven different polypeptides specifically cross-reacted with the different antibodies, indicating that multiple cAMP-PDEs are expressed in this tissue. On the basis of cross-reactivity with PDE4D but not PDE4A or PDE4B antibodies, 93- and 105-kDa PDE4D species were detected in the cortex and cerebellum extract. These forms are different from the 68-kDa PDE4D form expressed in endocrine cells after hormonal stimulation. Although the 93-kDa form was recovered in both the soluble and particulate fractions, the 105-kDa polypeptide was mostly particulate in the cortex and cerebellum extracts. PDE4B forms of 90-87 kDa were recovered in both soluble and particulate compartments of the brain extract. These forms were different from the previously identified PDE4A variants of 110 and 75 kDa. These data demonstrate that the presence of multiple cAMP-PDE genes is translated into cAMP-PDE proteins of different sizes and distinct immunological properties and that multiple variants derived from these cAMP-PDE genes are expressed in different regions of the brain and different subcellular compartments. These immunological tools will be useful to identify different cAMP-PDE forms expressed in organs targeted for pharmacological intervention with PDE4 inhibitors.

The population of GnRH-containing neurons showing socially mediated size changes project to the pituitary in a teleost, Haplochromis burtoni.

Reproductive function in all vertebrates is controlled by the brain-pituitary-gonadal axis. In teleost fish, endocrine cells within the adenohypophysis are grouped together and each collection of cells is innervated by specific neuropeptide fibers. An important regulatory step in reproductive control is gonadotropin-releasing hormone (GnRH), whose delivery to the pituitary is responsible for its release of gonadotropins. The hormone GnRH has been shown to play a critical role in the social control of reproduction in a teleost fish, Haplochromis burtoni. However, there has been no direct evidence that the preoptic area GnRH neurons project to the pituitary. In this study, we used a retrograde tracer and immunohistochemistry to identify those GnRH containing neurons that project to the adenohypophysis. We compared reproductively active territorial males with quiescent non-territorial males to discover whether the connectivity of the preoptic area GnRH neurons depends on the reproductive status of the male. We found that, irrespective of reproductive status, most GnRH neurons in the preoptic area project to the pituitary and that all of these GnRH neurons show the soma size change that has been associated with reproductive status in Haplochromis burtoni. Based on these data, we propose that there is a single population of GnRH containing cells in the preoptic area that change size as a function of reproductive state and that this entire population projects to the pituitary. This is the first direct demonstration that this essential circuit, linking GnRH neurons in the preoptic area to the pituitary, exists.

Diazepam facilitates stimulation-induced feeding in rats.

The effect of diazepam on the trade-off function between current and frequency for stimulation-induced feeding was evaluated in five rats with electrodes implanted in medial forebrain bundle structures. Three of the five exhibited stimulation-induced feeding (SIF) in vehicle tests, while in the remaining two attention to food was interspersed with periods of high activity. In all cases diazepam facilitated stimulation-induced feeding; the expression of stimulation-induced feeding was observed at a dose of 2.5 mg/kg and 5.0 mg/kg, where tested, and frequency threshold shifts ranged from 10% to 25%. The degree of facilitation was consistent across currents in two of the four pairs of trade-off functions examined. The results suggest that diazepam can facilitate stimulation-induced feeding and its expression in feeding sites with a competing arousal component.

A double-blind placebo-controlled glucose challenge in bulimia nervosa: psychological effects.

Nineteen bulimic women and 22 age-matched controls were randomly assigned to receive 25 g of glucose or a placebo injection under double-blind conditions. Blood samples of glucose, insulin, and glucagon, and psychometric assessments of mood and food cravings were obtained 10 min before, and 0, 5, 10, 20, 30, 45, and 60 min after injection. Blood levels of the large neutral amino acids (LNAAs) tryptophan, tyrosine, leucine, valine, phenylalanine, and leucine were determined at 10 min before and 60 min after the injection. Bulimic subjects were found to report more symptoms of distressed mood throughout the entire monitoring period than controls. Five minutes following glucose ingestion the self-reports of depression, fatigue, anxiety, and bewilderment rose to a level among the bulimic subjects that was above that at baseline, and was higher than that of bulimia nervosa (BN) subjects receiving placebo. No comparable change in mood was observed among controls. Blood glucose levels were correlated with mood in the bulimic group, but not in controls. In addition, the glucose injection induced a heightened urge to binge in the bulimic group (compared to placebo at 10 and 60 min), whereas reducing food cravings (for sweets) in the controls (at 5 min). When collapsed across time and injection condition, the blood glucose level of bulimics was lower than that of controls. There were no differences in insulin response between the groups. The bulimic group was found to have lower baseline levels of blood tryptophan, whereas no differences in the tryptophan/LNAA ratio were observed either at baseline or following glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of bulimia with fenfluramine and desipramine.

Desipramine and fenfluramine were administered to bulimic patients in a 15-week study of double-blind, placebo-controlled, crossover design. The 22 patients in the study met DSM-III criteria for bulimia and were of normal weight. Twelve subjects were randomly allocated to the fenfluramine group, and 10 subjects received desipramine. Half the subjects in each group received the active drug in the first 6 weeks and half received placebo. There was a 3-week washout period, after which subjects were crossed over for the remaining 6 weeks. The Eating Disorder Inventory, profile of Mood States, bulimia symptom checklists, and Hopkins Symptom Checklist were administered at weeks 0, 2, 4, 6, 9, 11, 13, and 15. Subjects maintained a daily record of bingeing, vomiting, and laxative/diuretic abuse. Results indicated that both drugs had beneficial effects on bingeing and vomiting frequency, although a greater proportion of patients were identified who responded to fenfluramine than to desipramine. Fenfluramine and desipramine were also effective in reducing the psychological symptoms of bulimia, such as the urge to binge, and feelings of depression. Results suggest that direct alteration of central food intake regulatory centers can effectively control bulimia.