Medical management of orbital infection.
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Biomedical subjects
Publications and source records attributed to M S Edwards.
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Zinc, protein, cholesterol, phospholipids, alkaline phosphatase (AlPase), acid phosphatase (AcPase), adenosine-5-triphosphatase(ATPase) and histology were studied in testis of zinc-deficient mice. Zinc and protein decreased in the 3-week experiment whereas they increased in the 6-week experiment. Zinc is involved in several functions of the cell and is regulated by hormones. Inhibition of spermatogenesis indicates for decreased zinc levels in 3-week whereas the increase in 6-week experiment indicates for accumulation of zinc in oedomatous fluid and uncontrolled diffusion of zinc across the blood testis barrier. Glycogen decreased in the 3-week as well as 6-week experiments due to blockage of androgen and spermatogenesis. Cholesterol and phospholipids increased in the 3-week experiment and decreased in 6-week experiment as both the parameters are related to steroidogenesis. Zinc deficiency leads to aspermatogenic condition and comparatively less injury to non-germinal cells. This could have blocked the transport of material across the testis barrier and therefore might have increased AlPase levels. Increased AcPase, probably represents lysosomal enzymes, as the cell debris of disorganised epithelium are to be digested and removed. ATPase increased in 3-week experiment and can be correlated to increased demands of energy of testicular cells to overcome the insults of zinc deficiency whereas the decrease in 6-week experiment could be as a result of inhibition of spermatogenesis.
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Human peripheral blood neutrophils bear receptors for immunoglobulin G, FcRII, and FcRIII that differ structurally and functionally. We investigated the role of FcRII and FcRIII in the phagocytosis of group B streptococci (GBS) by measuring neutrophil uptake of radiolabeled type III GBS. The mean uptake of GBS opsonized with human serum containing complement and specific antibody was 76%, but when this serum was heated, the mean uptake was only 22%. A monoclonal antibody to FcRIII, Leu-11b, inhibited in a dose-dependent manner uptake of GBS opsonized with heated or intact serum to maxima of 40 and 30%, respectively. Conversely, a monoclonal antibody to FcRII, IV.3, inhibited by 77% the uptake of GBS opsonized with heated serum but had no effect when GBS was opsonized with intact serum. Leu-11b and IV.3 had an additive inhibitory effect with heated but not with intact serum. Neither monoclonal antibody inhibited the uptake of GBS opsonized with hypogammaglobulinemic serum. Therefore, FcRII is the primary mediator of the phagocytosis of GBS opsonized by antibody alone, whereas FcRIII plays a lesser role. Surprisingly, FcRII is not necessary for phagocytosis when complement is also present. FcRIII participates, to a limited extent, in phagocytosis of GBS opsonized with antibody whether or not complement is present. These findings suggest that the function of FcRII in triggering phagocytosis may be particularly important in host defense against type III GBS in the setting of complement deficiency of young infants.
The capsular polysaccharide of type III group B streptococci contributes substantially to the virulence of this organism. We explored the extent to which capsular polysaccharide influences neutrophil complement receptor interactions by using a poorly encapsulated strain (COH 31r/s), two well-encapsulated strains (M732 and M912), and strains produced from COH 31r/s by transposon mutagenesis that lacked capsule (COH 31-15) or had capsular polysaccharide lacking terminal sialic acid residues (COH 31-21). When tested with normal human serum, each strain had initially high bactericidal indices (85 to 96%). Monoclonal antibody blockade of neutrophil complement receptor 3 (CD11b/CD18) inhibited opsonophagocytosis to a significantly greater extent for the well-encapsulated strain than for the poorly encapsulated, asialo, or unencapsulated mutant strain. The addition of antibody with specificity for capsular polysaccharide reduced the inhibitory effect significantly for the encapsulated but not for the mutant strains. Blockade of neutrophil complement receptor 1 (CD35) effected only low-level inhibition. However, simultaneous blockade of complement receptors 1 and 3 augmented the inhibitory effect. When hypogammaglobulinemic serum was used as an antibody-free complement source, the initial bactericidal index was low (30% +/- 15%) for an encapsulated strain and was not affected for the mutant strains. Blockade of either neutrophil complement receptor 1 or 3 or the combination fully inhibited killing of the encapsulated strain. These results demonstrate that the type III group B streptococcal capsular polysaccharide regulates interactions with neutrophil complement receptors. We conclude that efficient phagocytic killing of encapsulated group streptococci in nonimmune serum requires ligation of complement receptors 1 and 3.
Ten patients with giant intradural spinal arteriovenous fistulas (perimedullary Types II and III) were treated with embolization alone (three patients) or in combination with surgery (seven patients). Their ages at the time of treatment ranged from 2 to 40 years, with a mean of 19.5 years. The indications for treatment included progressive myelopathy in five patients, spinal subarachnoid hemorrhage in four, and acute paraplegia in one. Associated conditions included Rendu-Osler-Weber syndrome in two patients, and Cobb's syndrome in two patients. In one patient, the cause of the fistula may have been related to epidural anesthesia traumatizing a low tethered cord. Angiographically, the fistulas were subclassified in three groups: a single-hole fistula supplied by a single feeding medullary artery (three patients); a single-hole fistula supplied by multiple medullary arteries (three patients); and multiple separate fistulas supplied by multiple medullary arteries (four patients). Eight patients were classified as perimedullary Type III and two as perimedullary Type II. Embolic agents were delivered from transarterial routes in 14 procedures and transvenous routes in 2 procedures. A total of 16 embolizations and 8 operations were performed in 10 patients. Seven patients were cured of their fistula (as demonstrated by angiography), two patients had 5% residual filling and are scheduled for future therapy. One refused a follow-up angiographic examination. Complications related to embolization included rupture of the anterior spinal artery by a detachable balloon, resulting in transient worsening of paraplegia with recovery to baseline. Transient worsening of symptoms after surgery was common, but all patients returned to baseline or better. Dramatic improvement was observed in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Delay in diagnosis of carcinoma of the breast is a significant cause of medical malpractice suits in the United States. Although less than one-third of the patients with carcinoma of the breast are less than 50 years of age, more than two-thirds of these suits involve women less than 50 years of age. To see whether or not there are medical factors that make diagnosis in young women more difficult, we reviewed all patient visits to the East Carolina University (ECU) Breast Clinic between 1 January 1988 and 30 June 1991. Women less than 50 years of age had many more patient visits (1,567 versus 838 visits) and many fewer carcinomas detected (38 versus 100 visits) than women who were more than 50 years old. The sensitivity and positive predictive value of mammography were significantly lower in young women than older women (68 versus 91 percent, p < 0.005, and 28 versus 53 percent, p < 0.001, respectively). Physical examination in young women was also less satisfactory. Tumors were more ill-defined and the percent that were easily palpable were significantly lower (45 versus 72 percent, p < 0.01). Furthermore, there was a basic difference in the reason tumors were not palpable in each age group. In older women, tumors were nonpalpable because they were small (mean size 1.0 versus 4.1 centimeters, p < 0.01), whereas in younger women, the non-palpable tumors were large (mean size 4.0 versus 3.4 centimeters), suggesting that they were not palpable because of background mammary density or diffuse growth pattern rather than size. Data from the Breast Cancer Detection Demonstration Project were analyzed and also suggested that carcinomas are more difficult to diagnose in young women. The percent of carcinomas that were not detectable by either mammogram or physical examination were inversely proportional to age and ranged from 36 percent at 40 years of age to 9 percent at 75 years of age. In addition, data from Blue Cross and Blue Shield and the ECU Breast Clinic indicated that it costs at least twice as much to diagnose each carcinoma in women less than 50 years of age. In conclusion, we believe that currently available techniques for diagnosis of carcinoma of the breast are not satisfactory for women less than 50 years of age and that this, rather than physician error, may account for the large number of malpractice suits in this age group.
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At deployment plus 60 days, we were busy preparing for the possibility of war while simultaneously providing pharmaceutical service for more than 25,000 people. We were anticipating the arrival of a new Deployable Medical Systems hospital, increased automation in the form of the Tri-Service Micro Pharmacy Computer system, and various improvements in reference materials. Experiences similar to ours were occurring throughout Saudi Arabia. Army pharmacy had been challenged. The challenge was accepted, and viewed as an opportunity to excel, by providing the best possible pharmaceutical care to conserve the fighting strength of our armed forces.
A line of mice had been developed which became obese when fed a commercial mouse breeder chow. This obese line was compared to a non-obese line at various ages to determine whether the type or amount of dietary fat would affect adipocyte size and number. Experimental diets containing beef tallow (38% of calories as beef fat and 2% as corn oil), corn oil (40% corn oil) or low fat (2% corn oil) were provided ad libitum at the time of weaning. Dorsoscapular subcutaneous fat pads were removed at 5, 6, 7, and 8 weeks and at 3, 6, 9, 12, 15, 18, and 21 months of age. Adipocyte size and number were determined histologically. Obese mice had enhanced adipocyte hyperplasia compared to the non-obese line. Only when eating the low fat diet did the obese mice have life-long elevated hypertrophy compared with their non-obese counterparts since non-obese mice responded to high fat feeding with a dramatic increase in adipocyte volume, regardless of type of fat. Body weight was greater in the obese line at all ages studied; however, some overlap in body weight was encountered between non-obese mice fed the high fat diets and genetically obese mice. Non-obese mice fed the low fat diet were smaller than mice in all other treatment groups throughout the study. Weight of the dorsoscapular subcutaneous adipose tissue was consistently greater in the obese line; however, high fat feeding greatly increased fat pad weight in non-obese mice.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Cell kinetics and clinical behavior were correlated for 22 primary and 10 recurrent or metastatic medulloblastomas from 30 patients. METHODS: Twenty-six patients received bromodeoxyuridine (BUdR) intravenously during craniotomy; excised specimens were stained by the immunoperoxidase method. The BUdR labeling index (LI) was calculated. Four patients received a pulse of tritiated thymidine; LI was calculated autoradiographically. RESULTS: The mean LI for 32 tumors (11.7 +/- 1.3% standard error) indicated high proliferative potential. LI appeared higher in tumors from younger patients and those in the cerebellar hemisphere as compared with those in the cerebellar vermis. LI did not correlate with survival time. In six BUdR-labeled tumors labeled with iododeoxyuridine, the S-phase duration was 6.1-11.3 hours (mean, 8.0 +/- 0.8 hours); the potential doubling time was 25-82 hours. The actual doubling time, estimated in three cases from serial imaging, was 20-24 days. A cell loss factor of approximately 0.90 was assumed. CONCLUSION: A high LI may reflect rapid medulloblastoma growth, but survival seemed more dependent on sensitivity to radiation therapy.
In 43 pediatric patients (29 male, 14 female) with primary astrocytic tumors of the central nervous system (CNS), the correlation was evaluated between outcome and proliferative potential, measured by the bromodeoxyuridine (BrdU) labeling index (LI). Twenty-five patients had low-grade gliomas, 13 had anaplastic gliomas, and 5 had glioblastomas multiforme (GBM). All patients underwent surgery; 37 also had chemotherapy, radiation therapy, or both. The median BrdU LIs were less than 1% (range 0-9.3%) in low-grade gliomas, 2.3% (range 0-21.2%) in anaplastic gliomas, and 7.7% (range 0-21.3%) in GBM. Seven of eight patients with BrdU LI greater than 5% have died (median survival 29 weeks). Median survival has not been reached in patients with BrdU LI less than 1% (19/22 alive) or between 1% and 5% (12/13 alive) after median follow-up periods of 165 and 120 weeks, respectively. A high BrdU LI correlated with short survival (p = 0.0001); the association between malignant histology and short survival was weaker (p = 0.019). BrdU LI is therefore a significant predictor of outcome in patients with primary CNS astrocytomas and appears to be a stronger predictor than histology in patients with low-grade and anaplastic gliomas. More patients need to be studied to confirm these preliminary observations.
The usefulness of histopathological grading in predicting the prognosis of patients with ependymomas is controversial. To clarify the discrepancy between the histological malignancy and the prognosis of these tumors, we estimated the proliferative potential of 32 intracranial and intraspinal ependymomas and correlated the findings with the clinical behavior. Each patient received an intraoperative infusion of bromodeoxyuridine (BUdR, 200 mg/m2 i.v.) before tumor removal; the BUdR labeling index (LI), or percentage of BUdR-labeled cells, was determined immunohistochemically in excised specimens. The mean BUdR LI (+/- SD) of intracranial malignant ependymomas was 4.1 +/- 2.8%. Nonmalignant intracranial and intraspinal ependymomas and subependymomas had mean LIs of 1.5 +/- 0.9%, 1.1 +/- 0.3%, and less than 1%, respectively. Overall, 44% of the tumors recurred. There were no statistically significant differences in the recurrence rates of intracranial and intraspinal ependymomas, including subependymomas (43% and 44%, respectively), or of intracranial ependymomas with LIs greater than 1.0% and less than 1.0% (67% and 44%, respectively). However, the early recurrence rate (within 24 months after treatment) of tumors with LIs greater than 1.0% was higher than that of tumors with LIs of less than 1.0% (100% vs. 25%, P less than 0.05). The BUdR LI also showed a statistically significant inverse correlation with the time to recurrence. These findings indicate that BUdR LI reflects the proliferative potential of individual ependymomas and can be used to help predict the recurrence and estimate the prognosis of these tumors.
Between February 1984 and September 1990, 60 patients with brainstem gliomas were treated with hyperfractionated radiotherapy in the Department of Radiation Oncology at the University of California, San Francisco. Forty-one children (< or = 18 years) and 19 adults were treated with 100 cGy twice daily with 4-8 hr between doses. Thirty-one patients (21 children and 10 adults) received total doses of 66-72 Gy and 29 patients (20 children and nine adults) received 74-78 Gy. Median follow-up was 208 weeks for all patients (214 weeks for children, 157 weeks for adults). Twenty-three patients (14 children and nine adults) were alive at the time of analysis, surviving 59-359 weeks following treatment. Median actuarial survival was 73.6 weeks overall (72 weeks for children, 190 weeks for adults; p = 0.43). Survival at 12 and 24 months was 65% and 38%, respectively (63% and 32%, for children; 68% and 53% for adults). All patients had pretreatment magnetic resonance imaging by which tumors were classified as either focal or diffuse. No significant pretreatment prognostic factors for adults were identified. In children, significant favorable prognostic factors on univariate analysis were older age (p = 0.001), tumor location in thalamus or midbrain (p = 0.002), focal appearance on MRI scan (p < 0.001) and duration of symptoms > 2 months prior to treatment (p < 0.001). Thirty-five patients had tumor biopsies, leading to a diagnosis in 33 (22 children and 11 adults). Children with moderately anaplastic astrocytomas survived significantly longer than those with glioblastoma multiforme or unbiopsied tumors (p < 0.001). Only duration of symptoms > 2 months remained significant as a favorable prognostic indicator for children on multivariate analysis (p < 0.001). Survival was not significantly different for patients receiving < or = 72 Gy and those receiving > 72 Gy (p = 0.18). No subgroup of patients showed significantly better survival with the higher dose. These findings indicate that hyperfractionated radiotherapy is effective treatment for adults and a subgroup of better prognosis children with brainstem gliomas. There is a subgroup of pediatric patients with extremely poor prognosis for whom even this aggressive treatment does little to extend survival. We conclude that there is no benefit to increasing total dose above 72 Gy for any of the groups analyzed.
An infant had a giant congenital nevus, neurocutaneous melanosis (NCM), and a Dandy-Walker malformation of the brain. The diagnosis of NCM was suspected at 6 weeks of age when macrocephaly was noted, resulting in the discovery of hydrocephalus and a Dandy-Walker malformation. Serial magnetic resonance imaging scans demonstrated so-called T1 shortening in the pia or subarachnoid spaces surrounding the cerebellar vermis and in the temporal lobes anterior to the temporal horns. Eventually, a biopsy-proved melanoma developed in the anterior temporal lobe, in an area previously noted to have T1 shortening. Since meningeal cells have been shown experimentally to play a critical role in cerebellar development, we hypothesize that the association of NCM with a Dandy-Walker malformation may be due to meningeal melanosis disrupting the normal development of the cerebellum and fourth ventricle.
Serotype III strains of group B streptococci (GBS) are isolated from the majority of young infants with bacteremia or meningitis. We hypothesized that serotype-associated differences in structure of the type-specific capsular polysaccharide or the presence of c protein would influence the extent to which C3 degradation occurs on GBS and that type-specific antibody would alter C3 deposition or degradation patterns. When clinical isolates of GBS representing serotypes Ia, Ib/c, II (with or without c protein) and III were employed with hypogammaglobulinemic serum as an opsonic source, a remarkable similarity was observed in patterns of C3 deposition and degradation for each of the four GBS serotypes and between strains with or without c protein. Both C3b and iC3b were detected by 5 min and throughout a 90-min opsonization interval. Less deposition occurred at 5 min on serotypes Ia and Ib/c than on types II and III GBS. Minimal degradation to C3d or smaller fragments was observed. Type-specific antibody facilitated C3b deposition on GBS and C3b degradation to iC3b early in opsonization. Possibly, accessibility of C3 fragments to neutrophil receptors, rather than the extent to which the surface permits C3 degradation, accounts for differential virulence among GBS serotypes.