Safety of GM-CSF in Patients with AIDS: A Review of the Literature

We performed a literature search for all clinical studies reporting outcomes in patients with the acquired immunodeficiency syndrome (AIDS) receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) for any indication. Safety outcomes included human immunodeficiency virus replication, immune status, and frequency of opportunistic infections and neoplasms. Data were synthesized qualitatively. We identified 22 studies (274 patients): 12 addressed AIDS neutropenia, 8 AIDS cancer therapy, and 2 opportunistic infections. Viral burden was assessed by serum p24Ag in 15 studies. Nine reported no change in levels, three net decreases, and three net increases. All studies showing net increases involved patients receiving GM-CSF without a concurrent antiretroviral. The CD4 counts were unchanged in 5 studies, increased in 3, and not reported in 14. The incidence of neoplasms or new opportunistic infections was low. The literature suggests no increased risk of viral replication or clinical deterioration in patients with AIDS who take GM-CSF concurrently with zidovudine.     

MOBILITY AIDS FOR CHILDREN WITH HIGH-LEVEL MYELOMENINGOCELE: PARAPODIUM VERSUS WHEELCHAIR

The optimal method for providing mobility for children with myelomeningocele remains controversial. 39 children using a parapodium were compared with 29 children in wheelchairs. There were no significant differences between the two groups for medical complications, use of health-care services or activities of daily living, although there were differences in the patterns of complications. Children using the parapodium were more likely to develop lesions of the lower extremities, to have dislocated hips, to be more obese and to watch more television; children using wheelchairs were more likely to develop lesions of the gluteal region, to have knee-flexion contractures and to have fewer fecal accidents. The parapodium was judged by families to be less effective as a mobility aid; however, the upright posture it allows was considered extremely advantageous. A combined approach allowing upright posture and wheeled mobility would appear to be optimal.     

Differences in leisure-time physical activity levels between blacks and whites in population-based samples: The Minnesota heart survey

Energy expenditure in leisure-time physical activity (LTPA) was measured using the Minnesota LTPA Questionnaire in 35- to 74-year-old black and white residents of Minneapolis-St. Paul, Minnesota. Estimates of the geometric mean LTPA energy expenditure were 129 and 204 kcal per day for black and white men (p<.05) and 91 and 123 kcal per day for black and white women (p<.05). The percentage of individuals expending 2000 kcal or more per week in LTPA was significantly lower in black men than white men (25 vs. 35%; p=.01) but was not different in black versus white women (18 vs. 17%). Although black men and women reported greater occupational physical activity than their white counterparts, LTPA and job activity were unrelated in all race and sex groups. In both races, LTPA energy expenditure declined with age. LTPA increased with level of formal education, and the largest LTPA difference between blacks and whites was observed in those who had a high-school diploma or less. Blacks had lower participation rates than whites in most of the individually assessed physical activities. Additional research is needed on the determinants and promoters of LTPA in population subgroups.The research was funded by National Heart, Lung, and Blood Institute Research Grant R01 HL 23727 and National Research Award T32 HL 07328-10.     

External fixation of lower limb fractures in children.

Thirty-four tibial and femoral shaft fractures in 32 children between the ages of 3 and 15 years were treated by external fixation over a 5-year period. The indications were fractures occurring in association with other major injuries and failure of conservative treatment to maintain satisfactory reduction. There was one case of delayed union and one early refracture. The overall pin track infection rate was 6%, but the rate for the tibial pins (2.1%) was much lower than for the femoral pins (10.3%). Union was achieved at an average of 11.7 weeks in the femoral fractures and 10.0 weeks in the tibial fractures. The use of external fixation is recommended for childhood femoral and tibial fractures, particularly in children with multiple injuries.     

Executive cognitive deficits in primary dystonia.

Primary dystonia is a disorder of movement for which no consistent pathophysiology has been identified; in the absence of evidence to the contrary, it is assumed to be cognitively benign. We have studied a clinically heterogeneous group of 14 patients with primary dystonia on a battery of neuropsychological tests. Despite well-preserved speed of information processing, language, spatial, memory and general intellectual skills relative to normal controls, we have identified a constellation of attentional-executive cognitive deficits on the Cambridge Neuropsychological Test Automated Battery (CANTAB). Specifically, patients demonstrated significant difficulties negotiating the extra-dimensional set-shifting phase of the IED task. The implications of these findings for the pathophysiology of primary dystonia are discussed. This is, to the best of our knowledge, the first report of a significant cognitive deficit in patients with primary dystonia.     

Arthroscopic distal clavicle resection

The acromioclavicular joint is a potential source of pain in the shoulder. There are a variety of disorders that can affect this joint, including distal clavicle osteolysis, posttraumatic arthritis, osteoarthritis, and rheumatoid arthritis. Nonoperative treatment for this condition with nonsteroidal medication and activity modification can alleviate the pain. When conservative treatment is exhausted, surgical resection of the distal clavicle is often necessary. Arthroscopic resection of the distal clavicle preserves the acromioclavicular ligaments to prevent postoperative distal clavicle instability. The procedure is performed in either the beach chair or lateral position and requires the use of a shaver, electrocautery, and a burr for soft tissue and debridement and bone resection.     

Early experience with a novel plaque excision system for the treatment of complex coronary lesions.

The use of directional coronary atherectomy (DCA) in current practice has been limited. The SilverHawk System is a newly developed plaque excision device that aims to overcome the drawbacks of prior DCA platforms. The device was evaluated in a porcine coronary model and in a series of patients. Procedural variables along with outcomes were reviewed. Quantitative angiography (QCA) was performed and excised tissue fragments were weighed and examined histologically. In porcine cases, pretreatment MLD increased from 0.51 +/- 0.26 to 2.36 +/- 0.59 mm postdebulking and 19.9 +/- 7.6 mg of tissue was retrieved. In human cases, pretreatment MLD increased from 0.8 +/- 0.4 to 2.2 +/- 0.5 mm postdebulking and 15.2 +/- 7.8 mg of tissue was retrieved without complications. These data show that the SilverHawk System may offer significant utility in treating a wide variety of complex coronary lesions.     

Effect of the Aldehyde Dehydrogenase Inhibitor, Cyanamide, on the Ex Vivo Sensitivity of Murine Multipotent and Committed Hematopoietic Progenitor Cells to Mafosfamide (Asta Z 7557)

The ex vivo sensitivity of murine multipotent (CFU-GEMM) and committed (CFU-Mk, CFU-GM, BFU-E and CFU-E) hematopoietic progenitor cells to mafosfamide was quantified with and without concurrent exposure to cyanamide, an inhibitor of aldehyde dehydrogenase activity. In the absence of cyanamide, CFU-GEMM, CFU-Mk and CFU-GM were approximately equisensitive to mafosfamide while the erythroid progenitors were more sensitive to the drug. Cyanamide potentiated the cytotoxicity of mafosfamide toward CFU-GEMM and CFU-Mk, but not toward CFU-GM, BFU-E and CFU-E. Cellular aldehyde dehydrogenases are known to catalyze the oxidation of 4-hydroxycyclophos-phamide/aldophosphamide, the major intermediate in cyclophosphamide and mafosfamide activation, to the relatively nontoxic acid, carboxyphosphamide. Thus, our findings indicate that 1) murine CFU-GEMM contain the relevant aldehyde dehydrogenase activity, and 2) the relevant aldehyde dehydrogenase activity is retained upon differentiation to progenitors committed to the megakaryocytoid lineage, but lost upon differentiation to progenitors committed to the granulocytoid/monocytoid and erythroid lineages. The relative insensitivity of CFU-GM to mafosfamide is apparently due to a cellular determinant that influences their sensitivity to all cross-Unking agents since CFU-GM were found to be relatively insensitive to non-oxazaphosphorine cross-linking agents as well.     

Infantile myofibromatosis

 Infantile myofibromatosis is a mesenchymal tumor most commonly seen in infancy. The tumors have a variable appearance on CT/MR and often simulate a more aggressive neoplasm. This report describes CT/MR findings in cases of infantile myofibromatosis with pathologic correlation. Discussion into the success of imaging in suggesting the correct diagnosis is also addressed. Infantile myofibromatosis is a mesenchymal disorder of infancy characterized by the presence of tumorous nodules in the skin, subcutaneous tissue, muscle, viscera, and bone. Cases of solitary and multiple lesions have been described. We present the clinical, histologic, and radiographic findings of one case of the solitary form of infantile myofibromatosis that was recently diagnosed at our hospital.