Effect of compressive follower preload on the flexion-extension response of the human lumbar spine.

Traditional experimental methods are unable to study the kinematics of whole lumbar spine specimens under physiologic compressive preloads because the spine without active musculature buckles under just 120 N of vertical load. However, the lumbar spine can support a compressive load of physiologic magnitude (up to 1200 N) without collapsing if the load is applied along a follower load path. This study tested the hypothesis that the load-displacement response of the lumbar spine in flexion-extension is affected by the magnitude of the follower preload and the follower preload path. Twenty-one fresh human cadaveric lumbar spines were tested in flexion-extension under increasing compressive follower preload applied along two distinctly different optimized preload paths. The first (neutral) preload path was considered optimum if the specimen underwent the least angular change in its lordosis when the full range of preload (0-1200 N) was applied in its neutral posture. The second (flexed) preload path was optimized for an intermediate specimen posture between neutral and full flexion. A twofold increase in flexion stiffness occurred around the neutral posture as the preload was increased from 0 to 1200 N. The preload magnitude (400 N and larger) significantly affected the range of motion (ROM), with a 25% decrease at 1200 N preload applied along the neutral path. When the preload was applied along a path optimized for an intermediate forward-flexed posture, only a 15% decrease in ROM occurred at 1200 N. The results demonstrate that whole lumbar spine specimens can be subjected to compressive follower preloads of in vivo magnitudes while allowing physiologic mobility under flexion-extension moments. The optimized follower preload provides a method to simulate the resultant vector of the muscles that allow the spine to support physiologic compressive loads induced during flexion-extension activities.     

The measurement of carnitine and acyl-carnitines: application to the investigation of patients with suspected inherited disorders of mitochondrial fatty acid oxidation.

We describe an improved radio-enzymatic method for the measurement of carnitine, short-chain acyl-carnitine and long-chain acyl-carnitine in plasma and tissue. An internal standard, hexadecanoyl-[CH3-3H]-carnitine was synthesised and used to improve the determination of long-chain acyl-carnitine. The between and within batch precisions were 10.4 and 7%, respectively. Control data for neonates, infants, children and adults in the fed and fasted state are documented. In addition we confirm the hypocarnitinaemia associated with pregnancy. Patients with medium-chain acyl-CoA dehydrogenase deficiency were studied during episodes of hypoglycaemia. In both fasted controls and patients there were high concentrations of short-chain acyl-carnitine, however in the latter group there were also low concentrations of free carnitine. We suggest that the monitoring of plasma carnitine and its derivatives is a useful adjunct to the investigation of children suspected to suffer from inherited disorders of mitochondrial beta-oxidation. We also describe a sample preparation procedure suitable for high performance liquid chromatographic analysis of specific acyl-carnitines from urine, plasma and tissue homogenates. The recoveries of acetyl-carnitine, octanoyl-carnitine and hexadecanoyl carnitine from urine were 101.5, 95 and 91% and from plasma 99.5, 91.5 and 85.5%, respectively. Acyl-carnitines (C2-C16) were analysed as their p-bromophenacyl derivatives by reverse-phase high performance liquid chromatography using a ternary gradient of acetonitrile/water/triethylamine phosphate. We report ten patients who excreted octanoyl-carnitine, hexanoyl-carnitine and in some cases a small amount of decanoyl-carnitine. In most of these cases suberylglycine and dicarboxylic acids were also detected by GC/MS. We had access to cultured fibroblasts from five of these patients and were able to demonstrate medium-chain acyl-CoA dehydrogenase deficiency by direct enzyme assay.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

Opiate receptor subtype binding in gerbil hippocampus is altered by forebrain ischemia

A role for endogenous opioids in trauma-induced brain injury has been supported by pharmacological studies. The present series of experiments were initiated to extend these observations by measuring opiate receptor subtype binding in gerbil hippocampus following 7 days recovery from a 10 min ischemic insult. Quantitative in vitro autoradiography was utilized to measure mu [( 3H]DAGO), kappa [( 3H]bremazocine + 10 microM morphiceptin + 100 nM DSLET), delta [( 3H]DSLET + 10 microM morphiceptin) and lambda [( 3H]naloxone + 300 nM diprenorphine) binding. While ischemic tissue samples at the level of the dorsal hippocampus showed complete loss of CA1 pyramidal cells, we observed no significant alterations in mu or delta binding suggesting a non-pyramidal cell localization of these receptors. Kappa binding decreased significantly to 88% of control in the CA1 and CA3 regions while lambda binding in the stratum lucidum (CA3) increased to 165% of control. Our results show that opiate receptor subtypes are differentially affected by an ischemic insult.     

Amnesia-reversal activity of a series of cyclic imides

A series of dihydro-1H-pyrrolizine-3,5(2H,6H)-diones were synthesized and evaluated for their ability to reverse electroconvulsive shock (ECS) induced amnesia in mice. Among the structure-activity relationships explored were the effects of ring size, the presence of heteroatoms (sulfur) in the ring system, and the introduction of alkyl substituents. The optimal ring size for the bicyclic system was 5.5 with dihydro-1H-pyrrolizine-3,5(2H,6H)-dione (3), although some activity was present in the corresponding 5.6 [hexahydro-3,5-indolizinedione (7)] and 6.6 [tetrahydro-2H-quinolizine-4,6(3H,7H)-dione (9)] analogues. Replacement of the C-1 carbon atom in compound 3 with a sulfur [dihydropyrrolo[2,1-b]thiazole-3,5(2H,6H)-dione (10)] abolished activity, and the introduction of methyl groups resulted in poorer biological profiles except when the substitution was made at the 7a position [dihydro-7a-methyl-1H-pyrrolizine-3,5(2H,6H)-dione (4)]. In several instances, hydrolysis of the parent bicyclic compound was carried out to furnish the corresponding lactam acids, which were further derivatized. Several exhibited interesting activity, especially the 5-oxo-2-pyrrolidinepropanoic acid derivatives such as 5-oxo-2-pyrrolidinepropanoic acid (12), 5-oxo-2-pyrrolidinepropanoic acid phenylmethyl ester (17), 5-oxo-2-pyrrolidinepropanoic acid (3-chlorophenyl)methyl ester (20), N-4-pyridyl-5-oxo-2-pyrrolidinepropanoic acid amide (25), and N-(2,6-dimethylphenyl)-5-oxo-2-pyrrolidinepropanoic acid amide (27). Compound 3 (CI-911; rolziracetam) was also observed to improve performance on a delayed-response task in aged rhesus monkeys and was selected for evaluation in cognitively impaired human subjects on the basis of its biological profile and a wide margin of safety in animals.     

The impact of hospital structure and restructuring on the nursing workforce.

OBJECTIVE: Health systems throughout much of the world have been subject to 'reform' in recent years as countries have attempted to contain the rapidly rising costs of health care. Changes to hospital structures (restructuring) have been an important part of these reforms. A significant impact of current approaches to restructuring is the loss of, or changes to, nursing management roles and functions. SETTING: Australian hospitals PRIMARY ARGUMENT: Little evaluation has been undertaken to determine the impact of hospital structure and organisational restructuring on the nursing workforce. CONCLUSIONS: There is some indication that nurses have experienced a loss of key management positions, which may impact on their capacity to ensure that adequate and safe care is provided at the ward level.     

Use of ultrasound to assess healing of a mandibular distraction wound.

PURPOSE: A standardized, noninvasive technique to assess healing of the mandibular distraction wound is not available. Current methods include clinical examination, plain radiography, and computed tomography. These imaging techniques are expensive and obligate the patient to serial radiation exposure. In addition, anatomic overlap and metal artifacts may obscure the distraction gap. In contrast, ultrasound has been shown to be a noninvasive, efficient, and inexpensive way to evaluate bone healing. The purpose of this study was to test the feasibility of ultrasound to evaluate an experimental mandibular distraction osteogenesis wound. MATERIALS AND METHODS: Distraction devices were placed via a submandibular incision into 24 minipigs. The protocol consisted of 0-day latency and distraction rates of 1, 2, or 4 mm/d for a 12-mm gap. The wounds were assessed in vivo after 0, 8, 16, and 24 days of neutral fixation. Ex vivo radiographs were used to estimate bone fill using a semiquantitative score. A semiquantitative ultrasound score was assigned, and the beam penetration depth was measured in millimeters. RESULTS: In all groups, clinical stability of the distraction wound increased with the duration of fixation. Plain radiographs, taken during neutral fixation, showed that the desired distraction gap was achieved and maintained. The ultrasound score increased with fixation time, whereas beam penetration depth decreased as expected. Ex vivo radiographs showed increasing bone fill score with time and paralleled the ultrasound score. CONCLUSIONS: The results of this feasibility study indicate that ultrasound is potentially useful for the assessment of bone formation in distraction osteogenesis wounds.     

Attachment style, childhood adversity, and behavioral risk among young men who have sex with men.

PURPOSE: To examine relationships among childhood adversity, attachment style (one's core beliefs regarding the self and others), and the following risk behaviors and contexts among young men who have sex with men (YMSM): homelessness, daily substance use, participation in sex work, involvement in the criminal justice system, and being out of school or work. METHODS: Using a targeted sampling approach, we recruited 569 YMSM aged 17-28 years from natural venues in New York City including bars, clubs, parks, and bus stations. Youth completed a structured interview assessing lifetime and current risk and protective contexts and behavior. Data were analyzed using univariate and multivariate statistical methods, including hierarchical logistic regression. RESULTS: After controlling for demographic characteristics and childhood adversity, YMSM with a fearful attachment style were more likely to have been homeless (OR 2.93, 95% CI 1.65-5.18), to have participated in sex work (OR 2.35, 95% CI 1.44-3.85), to use substances daily (OR 2.79, 95% CI 1.29-6.03), to have been involved in the criminal justice system (OR 2.04, 95% CI 1.38-3.01), and to be out of school/work (OR 2.47, 95% CI 1.47-4.15). Three subgroups were particularly vulnerable: YMSM who identified as heterosexual, or bisexual, and/or transgender. CONCLUSIONS: A fearful attachment style contributes to some YMSM remaining outside of the protective systems of family, school, and work, and is associated with risky contexts where they are less likely to encounter prosocial peers and adults. Further, it is associated with risk behavior. Although gay-identified youth are generally found to have poor outcomes when compared with the general population of adolescents, in the present report, YMSM who identified as heterosexual were at particular risk. Attachment theory can guide interventions by informing how individuals experience relationships and manage developmental transitions.     

Immunohistologic demonstration of myocardial proteins with applications.

The authors used antibodies specific for creatine kinase MB isoenzyme (CK-MB) and myosin light chain-1 (MLC-1) for immunohistologic staining. At appropriate dilutions of antibody, frozen sections of human heart muscle were positive for both CK-MB and MLC-1, whereas sections of human skeletal muscle were negative for both proteins. Staining for both CK-MB and MLC-1 also was demonstrated in an immature teratoma. Furthermore, staining was localized to the rhabdomyosarcomatous elements within the teratoma; other components of the tumor did not stain for CK-MB or MLC-1. Biopsies of skeletal muscle revealed that regenerative, but not intact normal or degenerating, fibers also contained CK-MB and MLC-1. Immunohistologic stains for CK-MB and MLC-1 may be useful as tumor markers and as markers for regenerative muscle fibers.