Demineralized bone matrix as a biological scaffold for bone repair

Experimental models were created in rat fibula to represent impaired bone healing so that biological deficiencies that cause bone repair to fail or to be delayed may be investigated. These models consist of a 4-mm-long segmental defect, created in rat fibula by osteotomy, and fitted with a 7-mm-long tubular specimen of demineralized bone matrix (DBM) over the cut ends of the fibula. The experiments in this study involved various modifications of the DBM scaffold designed to reduce its osteoinductive activity: steam sterilization (sDBM), ethylene oxide sterilization (eoDBM), trypsin digestion (tDBM), and guanidine hydrochloride extraction (gDBM). Bone healing was evaluated by bending rigidity of the fibula and mineral content of the repair site at 7 weeks post-surgery. The sDBM scaffolds resorbed completely by 7 weeks and hence this model was a nonhealing negative control. Rigidities in the unmodified DBM and tDBM groups were comparable, whereas in the gDBM and eoDBM groups it was significantly reduced. Histologically, in the 4-mm defects repaired with unmodified DBM, direct and endochondral bone formation in the scaffold and the defect resulted in a neocortex consisting of woven and lamellar bone uniting the broken bone by 7 weeks post-surgery. We conclude that the eoDBM and gDBM groups represent failure or delay of the bone repair process when compared with the unmodified DBM group in which the process is analogous to normal bone healing.     

The homeotic genespineless-aristapedia affects geotaxis inDrosophila melanogaster

The homeotic mutationspineless-aristapedia (ss ^a ) transforms the aristae into second tarsi. Flies with aSS ^a phenotype also show extremely positive geotaxis as measured in a Hirsch-type geotaxis maze. Other antennal mutants and flies with their aristae amputated do not show such extreme positive geotaxis. Deletion analysis has comapped the geotaxis effect withSS ^a in band 89C on the third chromosome. Finally, a biometrical analysis has detected additional genes on the X chromosome that also affects geotaxis.This work was supported by a Charles and Johanna Busch Memorial Award to T.R.M. and an Anne B. and James H. Leathem Scholarship Fund Award to P.A.M.Department of Biological Sciences and Bureau of Biological Research, Nelson Biological Laboratories     

Immune rabbit sera do not recognize antigenic variants of caprine arthritis-encephalitis virus isolated during persistent infection.

Isolates of caprine arthritis-encephalitis virus recovered 12 to 18 months after infection of goats were tested for neutralization by using rabbit antisera directed to the original inoculum virus. Only slight differences in neutralization kinetics between the long-term isolates and the original virus were detected, indicating that heterologous rabbit antisera do not detect antigenic variation of the neutralizing epitopes of caprine arthritis-encephalitis virus.     

Detection of Borrelia burgdorferi in human blood and urine using the polymerase chain reaction.

We investigated the use of the polymerase chain reaction (PCR) to detect Borrelia burgdorferi strain B-31 in human blood and urine experimentally inoculated with 5 and 1 borreliae/cm3, respectively, and to biotinylate a DNA probe specific for B. burgdorferi in the dot blot and Southern blot assays. When the blood and urine samples were subjected to PCR, a 370-bp amplified product was consistently visible on agarose gel electrophoresis after 30 and 45 cycles, respectively. The total human genomic DNA extracted from a 1-cm3 sample of inoculated blood was approximately 6.25 micrograms, and the total amount of B. burgdorferi DNA was estimated to be 0.01 pg/6.25 micrograms of the human DNA. For PCR, 2.5 micrograms of human DNA which contained the equivalent of 0.004 pg of borrelia DNA (approximately two borreliae) were used for enzymatic amplification. When 1/20 or 1/10 of the PCR-amplified products were used either for dot blot or Southern blot hybridization, the accessible copies of amplified B. burgdorferi DNA were sufficient for detectable hybridization to occur. PCR amplification of B. burgdorferi DNA in clinical specimens followed by dot blot hybridization may be a valuable adjunct or alternative to current but inadequate laboratory methods for the diagnosis of Lyme disease.     

Surface receptors on neutrophils and monocytes from immunodeficient and normal horses.

Surface receptors on peripheral blood neutrophils and monocytes from normal and immunodeficient horses have been studied. Sheep erythrocytes (SRBC) coated with IgG, IgM, and complement but not IgG(T), readily bound to normal equine monocytes and neutrophils. More than 4000 molecules of IgG were required to sensitize each SRBC for adherence to monocytes, and more than 12,000 molecules were required for adherence to neutrophils. Young horses with a severe combined immunodeficiency had an almost total absence of lymphocytes, but normal numbers of monocytes and neutrophils. The number of receptors for immunoglobulin, complement, and phytolectin on monocytes and neutrophils from immunodeficient animals were similar to those on the cells of normal horses. Although the precursor cells of lymphocytes of horses with combined immunodeficiency appear to be defective, no defect in the other cellular products of the bone marrow were apparent.     

Duodenal complications in necrotizing pancreatitis: Challenges of an overlooked complication

BackgroundDuodenal complications of necrotizing pancreatitis (NP) are challenging and understudied. We sought to characterize the demographics and clinical course of NP patients with duodenal complications.MethodsSingle institution retrospective review of 687 NP patients treated from 2005 to 2018.ResultsDuodenal complications developed in 40 (6%) patients including fistula in 11 (2%) and stricture in 29 (4%) patients. Patients with duodenal complications had increased computed tomography severity index (CTSI), degree of glandular necrosis, organ failure, infected necrosis, and disease duration. Mortality from NP was increased in patients with duodenal fistula (36%) compared to patients with duodenal stricture (7%) and patients without duodenal complications (9%). Surgical management of duodenal complications was required in 9/11 (82%) patients with fistula and 17/29 (59%) patients with stricture.ConclusionsDuodenal complications occurred in 6% of necrotizing pancreatitis patients. Sixty five percent of patients with duodenal complications required surgical correction. Duodenal fistula was associated with increased mortality.     

Weightbearing and Activity Restriction Treatments and Quality of Life in Patients with Perthes Disease

BackgroundWeightbearing and activity restrictions are commonly prescribed during the active stages of Perthes disease. These restrictions, ranging from cast or brace treatment with nonweightbearing to full weightbearing with activity restrictions, may have a substantial influence on the physical, mental, and social health of a child. However, their impact on the patient’s quality of life is not well-described.Questions/purposesAfter controlling for confounding variables, we asked (1) are restrictions on weightbearing and activity associated with physical health measures (as expressed by the Patient-Reported Outcome Measurement Information System [PROMIS] mobility, PROMIS pain interference, and PROMIS fatigue) of children in the active stages of Perthes disease? (2) Are these restrictions associated with poorer scores for mental health measures (PROMIS depressive symptoms and PROMIS anxiety)? (3) Are these restrictions associated with poorer scores for social health measures (PROMIS peer relationships)?MethodsBetween 2013 and 2020, 211 patients with Perthes disease at a single institution were assigned six PROMIS measures to assess physical, mental, and social health. Patients who met the following eligibility criteria were analyzed: age 8 to 14 years old, completion of six PROMIS measures, English-speaking, and active stage of Perthes disease (Waldenstrom Stage I, II, or III). Weightbearing and activity restrictions were clinically recommended to patients in the initial through early reossification stages of Perthes disease when patients had increasing pain, loss of hip motion, loss of hip containment, progression of femoral head deformity, increased hip synovitis, and femoral head involvement on MRI or as a postoperative regimen. Patients were categorized into four intervention groups based on weightbearing and activity regimen. We excluded 111 patients who did not meet the inclusion criteria. The following six pediatric self-report PROMIS measures were assessed: mobility, pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Of the 100 patients, 36 were categorized into the no-restriction regimen, 27 into the mild-restriction regimen, 25 into the moderate-restriction regimen, and 12 into the severe-restriction regimen at the time of PROMIS administration. The median (range) age at diagnosis was 8 years old (range 2 to 13 years). There were 85 boys and 15 girls. Eleven patients had hips in Waldenstrom Stage I, 10 were in Stage II, and 79 were in Stage III. Forty-four patients had hips classified as lateral pillar B and 47 patients as lateral pillar C. Nine patients had not reached the mid-fragmentation stage for appropriate lateral pillar classification by the time they took the PROMIS survey. ANOVA was used to compare differences between the mean PROMIS T-scores of these weightbearing/activity regimens. Results were assessed with a significance of p < 0.05 and adjusted for Waldenstrom stage, gender, age at diagnosis, and history of major surgery using multivariate regression analysis.ResultsAfter controlling for confounding variables, the mild- (β regression coefficient -15 [95% CI -19 to -10]; p < 0.001), moderate- (β -19 [95% CI -24 to -14]; p < 0.001), and severe- (β -25 [95% CI -30 to -19]; p < 0.001) restriction groups were associated with worse mobility T-scores compared with the no-restriction group, but no association was detected for the pain interference or fatigue measures. Weightbearing and activity restrictions were not associated with mental health measures (depressive symptoms and anxiety). Weightbearing and activity restrictions were not associated with social health measures (peer relationships). Earlier Waldenstrom stage was associated with worse pain interference (β 10 [95% CI 2 to 17]; p = 0.01) and peer relationships scores (β -8 [95% CI -15 to -1]; p = 0.03); female gender was linked with worse depressive symptoms (β 7 [95% CI 2 to 12]; p = 0.005) and peer relationships scores (β -6 [95% CI -12 to 0]; p = 0.04); and earlier age at diagnosis was associated with worse peer relationships scores (β 1 [95% CI 0 to 2]; p = 0.03). History of major surgery had no connection to any of the six PROMIS measures.ConclusionWe found that weightbearing and activity restriction treatments are associated with poorer patient-reported mobility in the active stages of Perthes disease after controlling for Waldenstrom stage, gender, age at diagnosis, and history of surgery. Weightbearing/activity restrictions, however, are not associated with pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Understanding how these treatments are associated with quality of life in patients with Perthes disease can aid in decision-making for providers, help set expectations for patients and their parents, and provide opportunities for better education and preparation. Because of the chronic nature of Perthes disease, future studies may focus on longitudinal trends in patient-reported outcomes to better understand the overall impact of this disease and its treatment.Level of EvidenceLevel III, therapeutic study.     

Optimal payment systems for health services

Demand-side cost sharing and the supply-side reimbursement system provide two separate instruments that can be used to influence the quantity of health services consumed. For risk-averse consumers, optimal payment systems--pairs of insurance and reimbursement plans--are characterized by conflict rather than consensus between patient and provider about the quantity of treatment. A model of conflict resolution based on bargaining theory is used to represent the outcome when the payment system creates divergences between desired demand and desired supply. Using that model, we describe the optimal combination of insurance and reimbursement systems that maximize consumer welfare.     

Establishing a capitation policy for mental health and substance abuse services in healthcare reform

In healthcare reform the evolution toward capitated payment systems raises many questions that are unique to behavioral healthcare providers. These issues include how to structure risk contracts, how to set appropriate prices and how to price and cover the severely mentally ill and uninsured. Two possible solutions to the pricing dilemma are described in this article: using prior-use experience for setting prices, with a DRG-type classification formula, and using a combination of past-use formulas and current utilization data.