Kresimir Banovac

The effect of etidronate on late development of heterotopic ossification after spinal cord injury.

Abstract Forty patients with spinal cord injury (SCI) and heterotopic ossification (HO) were treated with etidronate and followed after therapy to determine the effects of long-term medication on heterotopic bone formation. Eighteen patients had tetraplegia and 22 had paraplegia. Early diagnosis of HO (positive bone scintigraphy and negative radiographic findings of HO) was established by 3-phase bone scintigraphy using 99m technetium-labeled methylene diphosphonate. All patients underwent treatment with etidronate, first with intravenous administration of 300 mg/day for 3 days followed by an oral administration of 20 mg/kg/day for 6 months. Eleven patients (27.5%) developed radiographic evidence of HO from 1.5 to 6 years after therapy. A low degree of HO was found in these patients; 8 had grade I and 3 had grade II ectopic ossification (Brooker’s scale). The analysis of data showed that 2 different types of ectopic bone may form in the later stages after SCI. In 5% of patients, HO was found in the same anatomical site initially and finally, suggesting a “rebound” in mineralization of bone matrix not prevented by the administration of etidronate. The other type of HO was found in the majority of patients (95%) where the localization of HO showed different involvement of joints than initially, indicating de novo appearance of HO following SCI. The data suggest that etidronate given for a prolonged period in higher doses has, in addition to an inhibitory effect on crystal formation, a cellular effect on bone-forming cells.

Tissue distribution of antibiotics in the intervertebral disc

Study Design This study analyzed the distribution of antibiotics within the intervertebral disc of rabbits. Specimens were tested with specific antibodies against antibiotics using an immunofluorescent technique. Objectives The results were correlated to provide a rationale for perioperative prophylaxis of infection. Summary of Background Data Several groups of investigators and the recent data from our laboratory showed quantitative changes in penetration of antibiotics into intervertebral disc. No previous study has assessed antibiotic distribution in anulus fibrosus and nucleus pulposus. Methods Discs were obtained from rabbits after intravenous injection of penicillin or gentamicin. Antibiotics were localized in tissue sections using specific antibodies with a immunofluorescent method. Result Penicillin (negatively charged) and gentamicin (positively charged) penetrated the neutrally charged anulus fibrosus, but penicillin had less ability than gentamicin to penetrate into the negatively charged nucleus pulposus. Conclusion Our data suggest that penetration and distribution of antibiotics into avascular intervertebral disc is significantly influenced by the charge of antibiotics.

Prevention and Treatment Of Heterotopic Ossification After Spinal Cord Injury

Abstract Background/Objectives: Heterotopic ossification (HO) is a frequent, irreversible complication afterspinal cord injury (SCI). The objective of this article is to explain the etiology of HO; present new advances in prevention, diagnosis, and management of this complication; and provide a suggested algorithm for clinical management. Etiology: Although still hypothetical, trauma and overexpression of bone morphogenic protein(s) in traumatized soft tissue appear to play important roles as initiating factors of HO. Prevention: Preventive use of nonsteroidal antiinflammatory agents (NSAIDs) reduces the incidence of HO by a magnitude of 2 to 3. Management: Early determination of serum creatine phosphokinase may have a diagnostic value in predicting the onset and severity of HO, and an NSAID may be added to etidronate therapy in the initial inflammatory phase of HO formation until C-reactive protein Ieveis return to normal range. Surgery is indicated in a subset of patients, and a regimenthat includes radiation therapy may prevent postoperative recurrence. Conclusion: Significant progress has been made in the early prevention and management of HO. Further studies are needed to elucidate the etiology.

Increased muscle strength in paralyzed patients after spinal cord injury: Effect of beta-2 adrenergic agonist

The administration of beta-2 adrenergic agonists in experimental animals result in an increased strength of skeletal muscle. In this study, we evaluated whether a beta-2 adrenergic agonist, metaproterenol, had an effect on muscle size and strength in a group of patients with muscular atrophy following spinal cord injury. Ten male subjects were randomly divided into 2 groups and agreed to participate in a prospective, double-blind, placebo-controlled, and crossover study. Metaproterenol (80 mg/day), or placebo, was administered orally for a period of 4 weeks. Muscle strength was measured by a force transducer interfaced with a microcomputer. Muscle size was calculated and expressed as a cross-sectional area of upper arm and forearm using a formula. Metaproterenol induced a significant increase of muscle strength in both groups of subjects, compared with placebo (p < .001). Similarly, there was an increase in a muscle size in the forearm following the administration of metaproterenol. Our data indicate that beta-2 adrenergic agonists may improve both muscle strength and size in patients with muscular atrophy following spinal cord paralysis.

Evaluation of serum osteoblast mitogenic activity in spinal cord and head injury patients with acute heterotopic ossification

Study Design This was a blind, prospective study of the effect of sera from patients with spinal cord and head injuries on osteoblast proliferation. Objectives The authors studied whether a humoral factor that stimulates the formation of heterotopic bone is released into the circulation after a neural injury. Backgound Data Other authors have shown that a humoral osteoinductive factor may be released after head and spinal cord injuries. Methods Serum was obtained at certain times throughout the first 12 weeks post-injury and from control subjects. It was incubated with osteoblasts harvasted from fetal rats, as well as with fibroblast controls. Results There was a significant rise in serum mitogenic activity after injury in both groups. When patients that developed heterotopic ossification were compared to other patients and controls, no significant differences were seen. Conclusions This in vitro study fails to support a humoral mechanism for heterotopic ossification after spinal cord or brain injuries.

Penetration of glycopeptide antibiotics in nucleus pulposus

The penetration of the glycopeptide antibiotics vancomycin and teicoplanin into the nucleus pulposus of rabbits was studied. Blood samples were obtained at 0.5, 1, 4, 8, and 24 hours after intravenous administration of 30 mg/kg vancomycin or 16 mg/kg teicoplanin. Concentrations of antibiotics were determined in tissue specimens and serum samples by fluorescence polarization immunoassays. Antimicrobial activity in the nucleus pulposus was determined with an agar diffusion method using a strain of Micrococcus luteus as the indicator organism. A peak concentration of vancomycin in the nucleus pulposus was attained 8 hours after drug administration. Teicoplanin reached its maximum level and plateaued 1 and 2 hours, respectively, after injection, and it remained unchanged for the rest of the study. This microbiologic analysis showed that the nucleus pulposus contained an antimicrobial level of glycopeptide antibiotics after administration. Because rabbit nucleus pulposus is similar anatomically to that of humans, these results may have implications regarding the timing and choice of antibiotic administration.

Hypothermia in Patients With Chronic Spinal Cord Injury

Abstract Design: Retrospective analysis of medical records. Background/Objectives: To determine frequency and degree of hypothermic episodes in patients with chronic spinal cord injury (SCI). Setting: Veterans Administration Medical Center. Methods: Research involved analysis of body temperature records of 50 chronic patients with tetraplegia. All patients were men with a length of injury of 19 ± 6 years. Mean age was 53 ± 15 (SD) years. Data were derived from the computerized patient record database system of the Veterans Administration Medical Center. Results were classified into 3 groups: (a) hypothermia (<95°F), (b) subnormal temperature (<97.7°F), and normal temperatures (97.7°F to 98.4°F). Body temperature was recorded during hospitalization (minimum duration of 30 days) using an oral probe twice a day. Ambient temperature was controlled by a central air-conditioning system and maintained at 72°F to 74°F. Results: A total of 867 measurements of body temperature were evaluated; normal temperature was recorded 298 times (35%), subnormal temperature was recorded 544 times (63%), and hypothermia was recorded 25 times (3%). There were 15 patients with 30 hypothermic episodes; subnormal temperature was found in all 50 patients from 1 to 47 times. Regression analysis of age and duration of SCI showed a nonsignificant relationship with body temperature. Conclusions: Our data suggest that patients with tetraplegia after SCI have significant dysfunction of thermoregulation associated with frequent episodes of subnormal body temperature in a normal ambient environment. Further studies are needed to evaluate possible consequences of low temperatures on the general health of patients and to develop preventive interventions.

Treatment of heterotopic ossification after spinal cord injury.

A new protocol in management of heterotopic ossification (HO) was evaluated in 46 patients after spinal cord injury (SCI). A group of 24 paraplegic and 22 tetraplegic patients was involved in a prospective study. Diagnosis of HO was made by bone scintigraphy and radiographic evaluation. Patients were divided into two groups. Group I was made up of 33 patients with positive bone scintigraphy and negative evidence of HO and Group II was made up of 13 patients with positive bone scintigraphy and positive radiographic evidence of HO. Etidronate was started intravenously (300 mg/day) for three days followed by oral therapy for six months (20 mg/kg/day). Follow-up of patients was 15.7 +/- 8 months after SCI. In Group I, etidronate therapy prevented the development of HO in 79 percent of patients; in 21 percent of patients, a low degree of tissue ossification was found which was not clinically significant. In Group II, there was an inhibitory effect of etidronate on progression of soft tissue ossification in six patients. The remaining seven patients did not respond to therapy and showed an increased growth of HO. Our data indicate that etidronate may prevent HO in the majority of patients when administered at an early stage of HO development and in higher doses than are routinely recommended.

Morphologic and metabolic changes in rat osteoblast cultures during the dark reaction with 8-methoxypsoralen

The dark reaction of 8-methoxypsoralen (8-MOP) with cultured rat osteoblasts did not cause significant changes in cellular replication rates or in the synthesis of RNA and proteins. Microscopic examination, however, revealed that the dark reaction resulted in massive accumulation of perinuclear lipids and in the statistically significant enhancement of alkaline phosphatase activity. A sharp, and statistically significant, upsurge of lipid synthesis in osteoblasts preceded microscopically detectable accumulation of lipids and occurred only during the initial, but not during the subsequent stages of the dark reaction. These results suggest that in the course of the dark reaction the plasma membrane of osteoblasts is a target of psoralen.

Poster 509 Some Characteristics of Bone Fractures after Spinal Cord Injury

restrictive lung disease was being treated for pneumonia on an inpatient spinal cord injury unit when he sustained a cardiac arrest requiring intubation, aggressive fluid resuscitation, and an intensive care unit (ICU) stay of several days. While in the ICU, the patient developed a 6 x 6.5 cm unstageable deep tissue injury to his left ischial area. Initial attempts to promote wound healing included diuresis, offloading, moisture management, nutritional support, ultrasonic mist therapy, chemical debridement, and, subsequently, three bedside surgical debridements. Despite these interventions, significant necrotic tissue persisted in the wound bed. Further surgical procedures were not possible due to the patient’s poor medical condition, and the decision was made to pursue biological debridement. The patient underwent three cycles of maggot therapy each lasting 2-3 days utilizing 250-500 Lucilia sericata larvae covered with a custom dressing. Setting: Inpatient spinal cord injury unit. Results or Clinical Course: Following biodebridment, the wound base consisted of healthy granulation tissue. The patient was discharged home with subsequent successful wound healing. Discussion: Decubitus ulcers are a major source of morbidity and mortality in patients with spinal cord injuries (SCIs). Annual incidence in this group has been estimated to range from 20% to 31%, resulting in yearly health care costs in the United States exceeding one billion dollars. There is extensive literature on the successful use of biodebridement in wound care; however, few reports focus specifically on the SCI population. When placed in the wound bed, Lucilia sericata larvae selectively dissolve necrotic tissue and secrete antibacterial substances that assist in wound disinfection. Maggot therapy is inexpensive, relatively simple to implement, and may be superior to surgical alternatives in patients with significant medical comorbidities and/or a high risk of autonomic dysreflexia. Conclusions: Decubitus ulcers are a common and potentially life-threatening problem in patients with spinal cord injuries, and healthcare providers should be aware of biodebridement with medical maggots as a safe and effective means of non-surgical management.