Susan Smith

Comparison of Ct Scan Muscle Measurements and Isokinetic Trunk Strength in Postoperative Patients

The present study compared the computed tomography (CT) scan muscle area/muscle density and isokinetic trunk strength of a group of spinal surgery patients (35 males and 11 females) 3 months postoperatively. Analyses showed trunk strength means to be below 50% of gender-specific “normal” values obtained by evaluating a normative sample. Extensor strength was more significantly affected than flexors. Single-cut CT scans performed at the time of isokinetic trunk strength assessment demonstrated psoas and erector spinae atrophy through a significant decrease in muscle density, with only a trend towards decreased cross-sectional area. Findings also indicated that there was a significant correlation between increased mechanical trunk strength performance and greater muscle density on CT scan. Strength was significantly lower for the male patients undergoing spinal fusion compared with those undergoing disc excision. However, no significant difference was found in strength measures between: males with high versus low pain level and working versus nonworking males at the time of evaluation.

Increased Nerve and Blood Vessel Ingrowth Associated With Proteoglycan Depletion in an Ovine Anular Lesion Model of Experimental Disc Degeneration

Study Design. Nerves and blood vessel distribution in discs were localized immunohistochemically and correlated with the proteoglycan contents of normal and degenerate disc tissues. Objective. The aim of the present study was to systematically evaluate whether nerve and blood vessel ingrowth was associated with depletion of disc proteoglycans and degenerative changes in an established experimental model of disc degeneration. Summary of Background Data. Animal models of disc degeneration, allowing longitudinal study of pathogenic mechanisms, are limited. The ovine model enables systematic monitoring of blood vessel and nerve ingrowth during the development of disc degeneration after injury to the anulus fibrosus. Methods. Merino sheep received a controlled left anterolateral surgical defect in the outer anulus fibrosus of the L1–L2 and L3–L4 discs (lesion group); sham-operated controls received the retroperitoneal anterolateral approach only. Animals were killed 3, 6, 12, and 26 months postoperation, and the discs were collected for histology and compositional and morphologic analyses. Sagittal tissue sections were stained with toluidine blue and hematoxylin and eosin; Type IV collagen immunolocalization visualized blood vessel ingrowth, and nerves were immunolocalized using monoclonal antibodies to growth-associated protein (GAP-43), protein gene product 9.5, and glial fibrillary acidic protein. Results. Compositional and histologic results demonstrated early focal depletion 3–12 months postoperation of glycosaminoglycan associated with lesion development, increased blood vessel and nerve ingrowth, and infiltration of cells from the outer anulus fibrosus along the plane of the original defect. Blood vessel numbers in the outer to mid third of the anulus fibrosus were elevated in the lesion discs 3–6 months postoperation reaching a maximum at 12 months postoperation; nerves immunoreactive with protein gene product 9.5 (also maximal at 12 months postoperation) were often found associated (but not exclusively) with blood vessels, and some nerves were also reactive with GAP-43 and glial fibrillary acidic protein, but only at 12 months postoperation. Conclusions. Nerve and blood vessel ingrowth into the anulus fibrosis were strongly associated with proteoglycan depletion. The ovine anular lesion model of disc degeneration is a useful experimental model for the systematic evaluation of nerve and blood vessel development after anular injury.

Effect of penicillin prophylaxis on nasopharyngeal colonization with Streptococcus pneumoniae in children with sickle cell anemia.

Polyvalent pneumococcal vaccine and oral penicillin prophylaxis are frequently used in patients with functional or anatomic asplenia to protect them from fulminant Streptococcus pneumoniae sepsis. We studied nasopharyngeal colonization with pneumococci in 34 patients with sickle cell anemia (aged 6 months to 5 years) receiving penicillin prophylaxis and in 63 age- and race-matched comparison patients. Patients with sickle cell anemia had fewer positive initial pneumococcal nasopharyngeal cultures than did the comparison group (14.5% vs 34.4%, P = 0.03) and significantly lower carriage rates during the respiratory illness season of November to March (8.7% vs 40.5%, P = 0.005). Penicillin prophylaxis did not result in emergence of penicillin-resistant pneumococci or in an increased carriage rate of Haemophilus influenzae type b. Our data suggest a mechanism of action for penicillin prophylaxis and provide some evidence for the relative safety of this regimen.

Quantifying postoperative deficits of physical function following spinal surgery.

This study evaluates the degree of objectively quantified physical deconditioning of spinal surgery patients. The object is to evaluate the data in terms of the pain and disability claimed by 35 male and 11 female patients three months after spinal surgery. Among the males, two subgroups (i.e., disc excision or spinal fusion) were evaluated. All patients reported subjective indices of pain/disability and completed quantified tests of lumbar motion, sagittal trunk strength, lifting capacity, and bicycle ergometry. In general, true lumbar motion was markedly restricted to 50%-60% and trunk strength means were below 50% of gender-specific normative values. There were similar deficits for lifting capacity. Those who had spinal fusions tended to perform poorly, with a relatively high incidence of pain/disability. There were no differences found between the male group and subgroups who were gainfully employed or had a brief period of disability prior to surgery or had low subjective pain/disability. These results indicate that a patients subjective pain/disability were not a reliable measure of functional capacity by three months postoperatively. Regardless of working status, pain level, or brevity of disability, there was a significant loss of performance ability and risk of persistent dysfunction after surgical treatment.

Hematologic alterations during acute infection in children with sickle cell disease

In order to assess the hematologic features of acute bacterial infection in sickle cell anemia, we compared complete blood counts of 23 affected children with proven bacterial infection (Group A) to those of 22 patients with fever but without evidence of bacterial disease (Group B). Univariate and multivariate analyses of the data were carried out. Values for hemoglobin and platelet count were similar in Group A and Group B patients even though these measurements in both groups differed from base line steady state values. Absolute band counts were usually greater in Group A patients, but the sensitivity and specificity of elevated band counts as a diagnostic tool for bacterial infection were relatively low. We conclude that no aspect of the complete blood count can be used to guide major management decisions in febrile children with sickle cell anemia and potentially life-threatening infection.

DIFFERENTIAL SIGNALING THROUGH THE IL-2 AND IL-4 RECEPTORS IN LYMPHOCYTES FROM PATIENTS WITH X-SCID: EVIDENCE FOR A γ c INDEPENDENT IL-4 RECEPTOR. • 73

DIFFERENTIAL SIGNALING THROUGH THE IL-2 AND IL-4 RECEPTORS IN LYMPHOCYTES FROM PATIENTS WITH X-SCID: EVIDENCE FOR A γ c INDEPENDENT IL-4 RECEPTOR. • 73

EFFECTIVE IMMUNE RECONSTITUTION IN MICE AFTER CO-TRANSPLANTATION OF BONE MARROW AND MARROW STROMA TRANSDUCED WITH THE IL-7 GENE: GENE THERAPY FOR POST-BMT IMMUNE DEFICIENCY. • 40

Bone marrow transplant (BMT) is followed by a period of profound immune deficiency, which is a major problem in clinical BMT and is likely to be important for gene therapy directed at immunologic diseases, e.g., SCID or AIDS. We have previously shown that human IL-7 (huIL-7) induces early thymic reconstitution in syngeneic murine BMT recipients (C57/B6). Another approach to achieve the same effect as multiple IL-7 injections would be to co-transplant bone marrow stroma engineered to produce high amounts of IL-7. Murine bone marrow stromal cultures were transduced with the retroviral vector JZEN hIL-7/tk neo to express huIL-7 (>1000pg/106 cells/24hours). Mice received T cell depleted BMT (TCD-BMT) and 5×106 stromal cells transduced with the human IL-7 gene (IL-7STR) via tail vein injection. Control animals received the same TCD-BMT but were co-transplanted with stromal cells transduced with the LNCX vector, which expresses only the neomycin resistance gene (LN-STR). Co-transplantation of the IL-7STR resulted in enhanced thymic reconstitution by day 28. The mean thymic cell number was 110 ± 7.5×106 in normal mice, 88 ± 21×106 in IL-7STR mice, and 9.8 ± 6.7×106 for the LN-STR mice. Thymic subsets in IL-7STR and normal mice were comparable, but LN-STR mice had a block in early thymic maturation. T and B cell function was tested using the T cell mitogen ConA and the T-dependent antibody response to sheep RBC. Both proliferative responses to ConA and anti-SRBC titers developed sooner and were of greater magnitude in IL-7STR than in LN-STR mice. Transduced bone marrow stromal cells producing huIL-7 (1068-968 pg/106 transduced stromal cells/24hours) could be cultured from the thymus on D28 post-BMT. No toxic effects of the IL-7 STR have been observed in recipient mice, with follow up of 1 year. Thus, bone marrow stroma transduced to overexpress IL-7 has the same effects on post-BMT thymopoiesis as IL-7 injections. Clinical strategies using IL-7STR gene therapy may be useful in enhancing thymopoiesis in BMT, SCID gene therapy, or AIDS patients.

101: CHANGING PATTERN OF EARLY STOOL BACTERIAL COLONISATION|[quest]|

A prospective study of 45 infants, evenly divided for mode of delivery and type of feeding, was undertaken. Stools were obtained at 10 and 30 days(d) of age and specific culture media used to allow quantitative assessment of the following organisms: coliforms(C), enterococci, staphylococci, lactobacilli(L), bifidobaeteria(B) and total anaerobes. L and B were further differentiated using gas liquid chromatography. The results were as follows:** (when present) No influence of mode of delivery or feeding method was found. The results support the findings of two recent studies which suggested that an ecological change may have occurred in Northern Europe to the effect that bifidobacteria are no longer the predominant organism in the stool of the majority of normal infants during the first month of life.

889 PNEUMOCOCCAL SEPTICEMIA DESPITE PENICILLIN PROPHYLAXIS IN CHILDREN WITH SICKLE CELL ANEMIA

Mortality due to S.pneumoniae septicemia in infants and young children with sickle cell anemia (SCA) remains unacceptably high. Pneumococcal vaccine and prophylactic penicillin (PRO PCN) have been used to prevent these infections. We have routinely used PRO PCN since 1978 for all patients with homozygous SCA between 6 mo and 5 yr of age: 125 mg b.i.d. for infants <2 yrs of age and 250 mg b.i.d. for those >2 yr old. Compliance is maximized by means of regular reminders. 71 patients have received PRO PCN for a total of 204 person yrs. During the past 6 1/2 yrs, 7 episodes of S. pneumoniae bacteremia occurred in 6 children (3.4 episodes/100 person yrs); 3 events were fatal. S.pneumoniae infections occurred in 4 clinical settings: (1) A 6 yr old girl died of sepsis 13 months after we electively terminated 4 yrs of prophylaxis. (2) A 14 month old girl died of sepsis 2 weeks after her PCN prescription ran out and her parents failed to refill it. (3) After missing only 1 or 2 doses, a 4 yr old girl died and another patient survived 2 episodes of sepsis. (4) Bacteremic pneumococcal pneumonia developed within 12 hours of the last PCN dose in a 9 month old girl who was reported not to have missed any recent doses. No examples of PCN insensitive or resistant S. pneumoniae were seen. In conclusion, PRO PCN may reduce the frequency of S. pneumoniae sepsis, but strict compliance is required. Prolonged administration may be advisable, with the understanding that absolute protection is not achieved.

40 ORAL PENICILLIN (P) PROPHYLAXIS IN CHILDREN WITH IMPAIRED SPLENIC FUNCTION: A STUDY OF COMPLIANCE

Septicemia due to S. pneumoniae is a well known complication of splenectomy or splenic dysfunction. Although prophylactic oral P is often recommended as a supplement to patient education and pneumococcal vaccine as a means of preventing these serious and often fatal infections, poor patient compliance is used as an argument against this approach. Therefore, we studied compliance during a 10 mo. period in 43 high risk patients, 27 of whom were infants or young children with sickle cell anemia, 15 with prior splenectomy, and 1 after bone marrow transplant. Median age was 3 yr. (range 6 mo. to 19 yr.). All were instructed and most were regularly reminded to take P twice daily. Without knowledge of the patients or their parents, urine obtained at one or more clinic visits was tested for P by the Sarcina lutea inhibition method. 50 of 76 (66%) samples contained P. Of the 43 patients, 32 (76%) had urines positive for P at least once. 19 of 20 patients tested multiple times were positive on at least one occasion. Parents of children whose initial urines were negative for P were provided with written and verbal reminders, and repeat urines tended to be positive. Compliance was not clearly related to age, duration of P administration, diagnosis, or number of clinic visits. Based on these data, we conclude that poor patient compliance is not a valid argument against use of prophylactic oral P in patients at high risk of pneumococcal septicemia.