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Background: Aromatase inhibitors improve disease-free survival compared with tamoxifen in postmenopausal women with hormone receptor-positive breast cancer. The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial compared exemestane monotherapy with sequential therapy of tamoxifen followed by exemestane. The trial failed to show a statistically significant difference between treatment arms. A robust translational program was established to investigate predictive biomarkers. Methods: A tissue microarray was retrospectively constructed using a subset of patient tissues (n = 4631) from the TEAM trial (n = 9766). Immunohistochemistry was performed for biomarkers, classed into three groups: MAPK pathway, NF-kappa B pathway, and estrogen receptor (ER) phosphorylation. Expression was analyzed for association with relapse-free survival (RFS) at 2.5 and 10 years and treatment regimen using Kaplan-Meier curves and log-rank analysis. All statistical tests were two-sided. Results: In univariate analysis, ER167 (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.59 to 0.85, P < .001), IKK alpha (HR = 0.74, 95% CI = 0.60 to 0.92, P .005), Raf-1(338) (HR 0.64, 95% CI = 0.52 to 0.80, P < .001), and p44/42 MAPK(202/204) (HR = 0.77, 95% CI = 0.64 to 0.92, P = .004) were statistically significantly associated with improved RFS at 10 years in patients receiving sequential therapy. Associations were strengthened when IKK alpha, Raf-1(338), and ER167 were combined into a cumulative prognostic score (HR = 0.64, 95% CI = 0.52 to 0.77, P < .001). Patients with an all negative IKK alpha, Raf-1(338), and ER167 score favored exemestane monotherapy (odds ratio = 0.56, 95% CI = 0.35 to 0.90). In multivariable analysis, the IKK alpha, Raf-1(338), and ER167 score (P = .001) was an independent prognostic factor for RFS at 10 years in patients receiving sequential therapy. Conclusions: The IKK alpha, Raf-1(338), and ER167 score is an independent predictive biomarker for lower recurrence on sequential therapy. Negative expression may further offer predictive value for exemestane monotherapy.

The objective of this study was to test the hypothesis that an equine diet formulated with chelated trace minerals, organic selenium, yeast culture, direct-fed microbials (DFM) and Yucca schidigera extract would decrease excretion of nutrients that have potential for environmental impact. Horses were acclimated to 100% pelleted diets formulated with (ADD) and without (CTRL) the aforementioned additives. Chelated sources of Cu, Zn, Mn, and Co were included in the ADD diet at a 100% replacement rate of sulfate forms used in the CTRL diet. Additionally, the ADD diet included organic selenium yeast, DFM, and Yucca schidigera extract. Ten horses were fed the 2 experimental diets during two 42-d periods in a crossover design. Total fecal and urine collection occurred during the last 14 d of each period. Results indicate no significant differences between Cu, Zn, Mn, and Co concentrations excreted via urine (P > 0.05) due to dietary treatment. There was no difference between fecal Cu and Mn concentrations (P > 0.05) based on diet consumed. Mean fecal Zn and Co concentrations excreted by horses consuming ADD were greater than CTRL (P 0.05). In feces stockpiled to simulate a crude composting method, no differences (P > 0.05) due to diet were detected for particle size, temperature, moisture, OM, total N, P, phosphate, K, moisture, potash, or ammonia N (P > 0.05). Although no difference (P = 0.2737) in feces stockpile temperature due to diet was found, temperature differences over time were documented (P < 0.0001). In conclusion, the addition of certain chelated mineral sources, organic Se yeast, DFM, and Yucca schidigera extract did not decrease most nutrient concentrations excreted. Horses consuming organic selenium as part of the additive diet had lower fecal and urine Se concentrations, as well as greater fecal K concentrations.

The objective of this study was to test the hypothesis that feed additives such as chelated minerals, organic Se, yeast culture, direct-fed microbials, and Yucca schidigera extract would improve nutrient digestibility when included in an equine diet. Horses (Quarter Horse geldings 4.5 to 16 yr of age; mean BW 522 kg ± 46 kg) were acclimated to 100% pelleted diets formulated with (ADD) and without (CTRL) commercially available sources of the aforementioned additives followed by a 14-d collection period of feces and urine. Chelated sources of Cu, Zn, Mn and Co were utilized versus sulfated forms, at a 100% replacement rate. No significant differences among apparent the digestibility of DM, ADF, or NDF (P= 0.665, P = 0.866, P = 0.747, respectively) were detected between dietary treatments. Likewise, no differences in apparent digestibility of Cu (P = 0.724), Zn (P = 0.256), Mn (P = 0.888), Co (P = 0.71), or Se (P = 0.588) were observed. No differences were observed in serum Cu, Mn, or Co concentrations between ADD and CTRL at acclimation or collection time points (P > 0.05). While no difference in serum Zn concentrations were observed between ADD and CTRL groups at acclimation (P > 0.05), they were statistically higher at the collection time period for horses consuming CTRL (P 0.05). Serum Zn concentrations of horses consuming both ADD (P = 0.021) and CTRL (P 0.05) were observed in serum Mn concentrations. Serum Co concentrations increased over time in horses consuming both ADD (P = 0.001) and CTRL (P = 0.021). From acclimation to collection, whole blood Se concentration increased for horses consuming CTRL (P = 0.01) but not for ADD (P > 0.05). The results of this study indicate no effect on nutrient digestibility due to the inclusion of chelated minerals, organic Se, yeast culture, direct-fed microbials, and Yucca schidigera extract for horses at maintenance.

Aim A systematic review of treatment guidelines for metastatic colorectal cancer (mCRC) was performed to assess recommendations for monoclonal antibody therapy in these guidelines. Method Relevant papers were identified through electronic searches of MEDLINE, MEDLINE In Process, EMBASE and the Cochrane Library; through manual searches of reference lists; and by searching the Internet. Results A total of 57 relevant guidelines were identified, 32 through electronic database searches and 25 through the website searches. The majority of guidelines were published between 2004 and 2010. The country publishing the most guidelines was the USA (12), followed by the UK (10), Canada (eight), France (eight), Germany (three), Australia (two), Spain (two) and Italy (one). In addition, eight European and three international guidelines were identified. As monoclonal antibody therapy for mCRC was not introduced until 2004, no firm recommendations for monoclonal antibody therapy were made in guidelines published between 2004 and 2006. Recommendations for monoclonal antibody therapy first appeared in 2007 and evolved as more data became available. The most recent international, European and US guidelines recommend combination chemotherapy with the addition of a monoclonal antibody for the first-line treatment of mCRC. Second-line treatment depends on the first-line regimen used. For chemoresistant mCRC, cetuximab or panitumumab are recommended as monotherapy in patients with wild-type KRAS tumours. Conclusion The study indicates that recent treatment guidelines have recognized the role of monoclonal antibodies in the management of mCRC, and that treatment guidelines should be updated in a timely manner to reflect the most recently available data.

With the aim of achieving earlier diagnosis of congenital Trypanosoma cruzi infection, we assessed the usefulness of detecting specific IgA antibody by an ELISA. We evaluated 12 pregnant women chronically infected with T. cruzi, their newborn infants, and three additional neonates with parasitemia at birth. The IgA-specific antibody was detected by adapting the procedure for use of a commercial IgG ELISA, the Hemagen Chagas' Kit (Hemagen Diagnostics, Inc., Waltham, MA). Trypanosoma cruzi-specific IgA was detected in 10 (83%) of 12 mothers at delivery, in one of three parasitemic infants, and one of 12 newborns of the chronically infected women. Testing of 13 infants at six months of age revealed IgA in seven infants (54%), of whom four also had persistent T. cruzi-specific IgG. Detection of T. cruzi-specific IgA could provide a criterion for diagnosis of congenital infection in the absence of detectable parasitemia.

The objective of this study was to test the hypothesis that feed additives such as chelated minerals, organic Se, yeast culture, direct-fed microbials, and Yucca schidigera extract would improve nutrient digestibility when included in an equine diet. Horses (Quarter Horse geldings 4.5 to 16 yr of age; mean BW 522 kg ± 46 kg) were acclimated to 100% pelleted diets formulated with (ADD) and without (CTRL) commercially available sources of the aforementioned additives followed by a 14-d collection period of feces and urine. Chelated sources of Cu, Zn, Mn and Co were utilized versus sulfated forms, at a 100% replacement rate. No significant differences among apparent the digestibility of DM, ADF, or NDF (P= 0.665, P = 0.866, P = 0.747, respectively) were detected between dietary treatments. Likewise, no differences in apparent digestibility of Cu (P = 0.724), Zn (P = 0.256), Mn (P = 0.888), Co (P = 0.71), or Se (P = 0.588) were observed. No differences were observed in serum Cu, Mn, or Co concentrations between ADD and CTRL at acclimation or collection time points (P0.05). While no difference in serum Zn concentrations were observed between ADD and CTRL groups at acclimation (P0.05), they were statistically higher at the collection time period for horses consuming CTRL (P0.0001). Whole blood Se concentration was greater in the CTRL group versus the ADD group both at acclimation (P = 0.041) and collection (P = 0.005) time periods. In reference to time, serum Cu concentrations increased (P = 0.012) for animals consuming CTRL, but not ADD (P0.05). Serum Zn concentrations of horses consuming both ADD (P = 0.021) and CTRL (P0.0001) increased over time from acclimation to collection time points. No time differences (P0.05) were observed in serum Mn concentrations. Serum Co concentrations increased over time in horses consuming both ADD (P = 0.001) and CTRL (P = 0.021). From acclimation to collection, whole blood Se concentration increased for horses consuming CTRL (P = 0.01) but not for ADD (P0.05). The results of this study indicate no effect on nutrient digestibility due to the inclusion of chelated minerals, organic Se, yeast culture, direct-fed microbials, and Yucca schidigera extract for horses at maintenance.

The objective of this study was to test the hypothesis that an equine diet formulated with chelated trace minerals, organic selenium, yeast culture, direct-fed microbials (DFM) and Yucca schidigera extract would decrease excretion of nutrients that have potential for environmental impact. Horses were acclimated to 100% pelleted diets formulated with (ADD) and without (CTRL) the aforementioned additives. Chelated sources of Cu, Zn, Mn, and Co were included in the ADD diet at a 100% replacement rate of sulfate forms used in the CTRL diet. Additionally, the ADD diet included organic selenium yeast, DFM, and Yucca schidigera extract. Ten horses were fed the 2 experimental diets during two 42-d periods in a crossover design. Total fecal and urine collection occurred during the last 14 d of each period. Results indicate no significant differences between Cu, Zn, Mn, and Co concentrations excreted via urine (P0.05) due to dietary treatment. There was no difference between fecal Cu and Mn concentrations (P0.05) based on diet consumed. Mean fecal Zn and Co concentrations excreted by horses consuming ADD were greater than CTRL (P0.003). Differences due to diet were found for selenium fecal (P0.0001) and urine (P0.0001) excretions, with decreased concentrations found for horses consuming organic selenium yeast (ADD). In contrast, fecal K (%) was greater (P = 0.0421) for horses consuming ADD, whereas concentrations of fecal solids, total N, ammonia N, P, total ammonia, and fecal output did not differ between dietary treatments (P0.05). In feces stockpiled to simulate a crude composting method, no differences (P0.05) due to diet were detected for particle size, temperature, moisture, OM, total N, P, phosphate, K, moisture, potash, or ammonia N (P0.05). Although no difference (P = 0.2737) in feces stockpile temperature due to diet was found, temperature differences over time were documented (P0.0001). In conclusion, the addition of certain chelated mineral sources, organic Se yeast, DFM, and Yucca schidigera extract did not decrease most nutrient concentrations excreted. Horses consuming organic selenium as part of the additive diet had lower fecal and urine Se concentrations, as well as greater fecal K concentrations.

Aim A systematic review of treatment guidelines for metastatic colorectal cancer (mCRC) was performed to assess recommendations for monoclonal antibody therapy in these guidelines. Method Relevant papers were identified through electronic searches of MEDLINE, MEDLINE In Process, EMBASE and the Cochrane Library; through manual searches of reference lists; and by searching the Internet. Results A total of 57 relevant guidelines were identified, 32 through electronic database searches and 25 through the website searches. The majority of guidelines were published between 2004 and 2010. The country publishing the most guidelines was the USA (12), followed by the UK (10), Canada (eight), France (eight), Germany (three), Australia (two), Spain (two) and Italy (one). In addition, eight European and three international guidelines were identified. As monoclonal antibody therapy for mCRC was not introduced until 2004, no firm recommendations for monoclonal antibody therapy were made in guidelines published between 2004 and 2006. Recommendations for monoclonal antibody therapy first appeared in 2007 and evolved as more data became available. The most recent international, European and US guidelines recommend combination chemotherapy with the addition of a monoclonal antibody for the first-line treatment of mCRC. Second-line treatment depends on the first-line regimen used. For chemoresistant mCRC, cetuximab or panitumumab are recommended as monotherapy in patients with wild-type KRAS tumours. Conclusion The study indicates that recent treatment guidelines have recognized the role of monoclonal antibodies in the management of mCRC, and that treatment guidelines should be updated in a timely manner to reflect the most recently available data.

Atherosclerotic renal artery stenosis (ARAS) is an important cause of renal dysfunction and secondary hypertension, and is associated with adverse cardiovascular events and increased mortality. The natural history of ARAS is characterized by anatomic disease progression and/or renal dysfunction in only a minority of patients. Medical therapy for ARAS is directed primarily toward blood pressure control and cardiovascular risk factor reduction. Renal artery revascularization is an additional treatment option for ARAS associated with ischemic nephropathy or severe, poorly controlled hypertension despite aggressive medical therapy. Unfortunately, the benefits associated with revascularization versus medical therapy alone remain unproven. Renal artery revascularization may be accomplished through open surgical revascularization or angioplasty and stenting. Although surgical renal revascularization is associated with more durable results and relatively lower risk for postoperative renal function decline, the increased risk of death or major complications associated with this management approach limit its use in patients with significant comorbidities. Renal artery angioplasty and stenting is being utilized with increasing frequency but is of uncertain benefit and is associated with rates of post-intervention renal function improvement and deterioration that are approximately equal. Renal function outcomes associated with angioplasty and stenting may be improved through a selective treatment approach and utilization of distal embolic protection. Renal artery revascularization represents the only treatment alternative for patients unresponsive to medical management, and is therefore the ''treatment of choice'' in this select group. Results of ongoing randomized trials are eagerly anticipated and may provide useful guidance for future management of ARAS.

Elderly adults account for >40% of persons with invasive group B streptococcal (GBS) disease and for >50% of GBS-associated deaths in the United States. The prevalence of colonization among healthy elderly adults (approximately 25%) is similar to that among women of childbearing age. Delineating contributions of comorbid conditions, altered integrity of anatomical barriers, and abnormalities in immune responses caused by immune senescence to pathogenesis require further investigation. Delayed clinical recognition of illness may contribute to poor outcome. Skin and soft-tissue infections and bacteremia with no identified focus are common manifestations of infection in elderly adults and younger nonpregnant adults. Urinary tract infection and pneumonia are presentations more often encountered in elderly persons than in younger adults. The safety and immunogenicity of GBS serotype V-tetanus toxoid conjugate vaccine in healthy elderly persons suggest the potential for vaccination as an approach to prevention of invasive GBS infections in elderly persons.

To evaluate the predictability of shoulder dystocia using preconceptive and prenatal risk factors.Data from 1,622 term patients with prenatal care prior to 20 weeks who delivered single, vertex fetuses during a consecutive 12-month period were analyzed. Two groups were chosen. The first group was patients whose fetuses experienced shoulder dystocia during delivery (cases). The second group (controls) consisted of the remaining patients, whose fetuses had not experienced shoulder dystocia. The two groups were compared with regard to demographics and pregnancy characteristics.Factors not significantly different between the two groups included were obesity, multiparity, history of diabetes, short maternal stature, postdatism and advanced maternal age. The incidence of macrosomia was significantly higher (P.001) in cases (35.4%) than in controls (4.8%). Other factors associated with shoulder dystocia were previous shoulder dystocia, concurrent diabetes, prior delivery of a fetus4,000 g and excessive weight gain during pregnancy. Many factors previously associated with shoulder dystocia were found to be nonsignificant in our study.Macrosomia appears to be the single important factor associated with shoulder dystocia which, even in the presence of significant risk factors, remains largely unpredictable.

Our previous experience with early neurosurgery for lipomyelomeningocele revealed that patients undergoing repair before age 1.5 years were more likely to have normal bladder function. We evaluate the durability of the urological benefits in patients with lipomyelomeningocele with longer followup.A retrospective chart review was performed on all patients who underwent urodynamic testing before and after primary neurosurgical repair of lipomyelomeningocele. A total of 43 patients presented between 1983 and 1995 with at least 12 months of followup (median 68, range 15 to 167).Of the 43 patients 36 (84%) maintained stable clinical and urodynamic function, and 7 (16%) had late deterioration, which occurred between 9 months and 8 years postoperatively. Of 19 patients with normal urodynamic studies preoperatively 14 (74%) maintained normal function. Overall, 14 of 43 patients (33%) with lipomyelomeningocele had normal bladder and sphincter function during followup. The principal predictor of long-term normal bladder function was preoperative urodynamic status, since urodynamic studies were preoperatively normal in 13 of 14 patients (93%) who maintained normal bladder and sphincter function. Late neurosurgery was equally efficacious if urodynamic studies were normal.Our data continue to support early diagnosis and neurosurgical intervention in patients with lipomyelomeningocele, since there is a higher likelihood of normal preoperative function that can be preserved. Furthermore, the results are durable in 84% of cases. However, close followup is necessary, since deterioration can occur up to 8 years postoperatively.

Late-onset septicemia due to Enterococcus faecalis is common among very low-birth weight neonates. These infants have low concentrations of placentally derived IgG and developmentally low levels of complement. The aim of the present study was to determine the contribution of antibody to in vitro neutrophil-mediated phagocytosis of E. faecalis. Antibody alone, as contained in an adult serum pool heated to inactivate complement, promoted only a modest reduction in the initial bacterial inoculum (50 +/- 12%) for 6 of 10 E. faecalis bacterial strains tested and allowed growth of the other four strains. In the presence of complement, NHS promotedor = 90% reduction in the initial bacterial inoculum of two representative strains at serum concentrations as low as 0.5%. Hypogammaglobulinemic serum supported similar activity only at concentrations above 5%. Purification of IgG and IgM fractions from NHS revealed that IgM had the higher specific activity to promote phagocytic activity. Absorption to remove specific antibody significantly reduced bactericidal activity by normal human serum, complement-deficient sera, and hypogammaglobulinemic serum. Reconstitution of hypogammaglobulinemic serum with antibody as contained in 1% heated normal human serum or in immune globulin for intravenous use (1200 mg/dl) restored phagocytic activity. Thus, E. faecalis-specific antibody enhances PMN-mediated killing of this organism. Adjunctive therapy with intravenous immunoglobulin could augment the host response to enterococcal infections in infancy.

This analysis aimed to review the experience in the management of adult medulloblastoma at the University of California, San Francisco, and to identify important prognostic factors for survival and posterior fossa control.We performed a retrospective review of 34 adult patients, ageor = 15, with cerebellar medulloblastoma treated with radiotherapy at the University of California, San Francisco from 1970 to 1994. All patients underwent a surgical procedure (complete resection in 17, subtotal resection in 10, and biopsy alone in seven), followed by craniospinal irradiation. Most patients treated after 1979 also received chemotherapy. Twenty were classified as poor-risk due to either incomplete resection or evidence of disease outside of the posterior fossa at diagnosis.The 5-year posterior fossa control and overall survival rates were 61% and 58%, respectively. The majority of relapses occurred in the posterior fossa (14 of 17). Multivariate analysis revealed that age (favoring older patients), gender (favoring female patients), and extent of disease at diagnosis (favoring localized disease) were important prognostic factors for posterior fossa control. There was a trend toward improved posterior fossa control with higher radiation dose to the posterior fossa in patients with a complete resection. Gender and extent of disease at presentation were significant prognostic factors for survival. The 5-year survival rates were 92% for female patients versus 40% for male patients, and 67% for patients with localized disease versus 25% for those with disseminated disease. The prognosis following recurrence was poor; all died of the disease.Survival for adult medulloblastoma was comparable to its pediatric counterpart. In patients with localized disease at presentation, gender (favoring female patients) and age (favoring older patients) were important prognostic factors for posterior fossa control and survival. In patients with disseminated disease at presentation, the prognosis is poor, and innovative therapy is needed to improve survival.

Between March 9, 1984 and January 29, 1992, 42 children with newly diagnosed symptomatic or previously diagnosed progressive low-grade gliomas received outpatient chemotherapy as their primary treatment. This study was a single arm, phase II trial designed to estimate the time to tumor progression and toxicity of this regimen. Procarbazine, 6-thioguanine, and dibromodulcitol were given before lomustine (CCNU) and vincristine was given 1 and 3 weeks after CCNU. Patients were treated for six treatment cycles or until the tumor progressed, whichever came first. Twenty-three patients had juvenile pilocytic astrocytomas, 11 had astrocytomas, one had oligodendroglioma, one had ganglioglioma, and six had radiographically diagnosed low-grade gliomas. The mean age of the patients was 5 years (median, 3 years). The median time to treatment failure was 132 weeks (95% confidence interval: 106, 186 weeks). Only eight patients have died the estimated 5-year survival rate is 78% (95% confidence interval, 60% 87%). There were two episodes of grade 4 neutropenia, and three episodes of grade 4 thrombocytopenia. This regimen was safe, able to be delivered in the outpatient setting, and produced prolonged periods of disease stabilization in children with low-grade gliomas.

Primary intracerebral sarcomas are rare tumors. Malignant fibrous histiocytoma and fibrosarcoma are the predominant histologies. A 3 year old girl with a primary, intraparenchymal cerebral osteosarcoma, the second case reported in the literature, is described. Partial surgical resection, systemic chemotherapy and radio-surgery has provided tumor control at 18 months. Treatment issues are discussed.

This article reviews the effects of the physiologic changes accompanying pregnancy on the pharmacokinetics of antimicrobials commonly employed during pregnancy. The possible adverse effects on the fetus from maternal use of antibacterials and their excretion into breast milk are reviewed. Principles of antibiotic pharmacology in newborn infants are summarized. The indications for use, dosages, and potential for adverse effects are reviewed for antibiotics currently in use and for several agents for which approval is pending for use in the newborn.

We screened human primary and recurrent malignant glioma, juvenile pilocytic astrocytoma, medulloblastoma, and meningioma tissue specimens for alterations in p16 gene structure. Single strand conformation polymorphism (SSCP) analysis was used to screen for point mutations, and a quantitative polymerase chain reaction-based assay was used to screen for homozygous gene deletions. In malignant glioma specimens, homozygous p16 gene deletions were significantly more common in high-grade tumors than in low-grade gliomas. Point mutations causing alteration in predicted protein structure were not detected. Medulloblastomas showed rare homozygous deletions and no point mutations. No mutations were detected in meningiomas.

Objective: The purpose of this study was to prospectively test the null hypothesis that there is no difference in the clinical effectiveness of azithromycin and erythromycin for the treatment of chlamydia cervicitis in pregnancy. Methods: All antepartum obstetrical patients underwent routine screening for chlamydia cervicitis using a DNA probe assay (Gen-Probe Pace, San Diego, CA). Women who tested positive for chlamydia cervicitis were prospectively randomized to receive either azithromycin 1 g orally at enrollment, or erythromycin 500 mg orally 4 times a day for 7 days. Sexual partners were referred to the county health department for evaluation and treatment. A test of cure was repeated in 2 weeks. Results were analyzed by chi-square analysis and Fisher's exact test when indicated. Results: One hundred forty women tested positive for chlamydia cervicitis and agreed to randomization. There were 4 (6.2%) treatment failures in the azithromycin group and 18 (27.7%) in the erythromycin group (P = 0.005). Gastrointestinal side effects were reported by 42 (65.5%) of the women taking erythromycin, but only 12 (19.4%) of those taking azithromycin (P < 0.002). Gastrointestinal side effects and resultant noncompliance were significantly related to treatment failure with erythromycin. Conclusions: The findings of this study support the conclusion that a single dose of azithromycin is a significantly more effective and better tolerated treatment regimen for chlamydia cervicitis in pregnancy than erythromycin which is currently recommended.

A retrospective review including long-term follow-up (4.6-12.0 years) was performed of all 28 pediatric patients who underwent high-activity 125I brachytherapy at the University of California, San Francisco, for primary or recurrent brain tumors from 1980 until 1991. There were 4 glioblastomas, 11 high-grade nonglioblastoma multiforme (NGM) malignant gliomas, 10 contrast-enhancing low-grade NGM, 2 choroid plexus carcinomas, and 1 rhabdomyosarcoma. The 13 survivors included 7 of 8 patients with primary high-grade NGM, 2 of 3 patients with primary low-grade NGM, and 3 of 7 patients with recurrent low-grade NGM. Necrosis (with or without tumor) was identified in 17 of 22 reoperated patients. The mean Karnofsky performance status was 88 +/- 9 at the time of brachytherapy, 87 +/- 7 at 3 years, and 87 +/- 9 in 11 patients alive at 6-12 years. Brachytherapy is a useful modality for treating selected pediatric brain tumors, and although focal necrosis is a common sequela, it does not tend to have a major impact on the Karnofsky performance status, if the implant site is amenable to reoperation.

Ganglion cysts that compress the common peroneal nerve frequently arise from the proximal tibiofibular joint. In a 60-year-old man, the nerve was compressed by a cyst that arose from the lateral meniscus and extended around the posterolateral aspect of the fibular neck. The origin and extent of the lesion, which could not be determined by clinical examination, was seen through magnetic resonance imaging. Cysts arising from the lateral meniscus should be considered in the differential diagnosis of compression of the common peroneal nerve.

The purpose of this study was to evaluate the accuracy of antenatal ultrasonography in the detection of fetal anomalies among twin gestations cared for in a specialized antepartum twin clinic. A retrospective study was performed of 245 consecutive twin gestations followed in our twin clinic. The sensitivity, specificity and diagnostic indices of ultrasound to detect prenatal anomalies in the 490 infants delivered from July 1988 to October 1994 were determined. Fourteen infants had isolated congenital anomalies, and ten had multiple anomalies. The overall prevalence of congenital anomalies was 4.9%. Antepartum ultrasound examination had a sensitivity of 88% and a specificity of 100% for the detection of an anomalous infant, with a positive predictive value of 100% and a negative predictive value of 99%. The sensitivity of ultrasound for each individual anomaly within the cohort was 82%, with 100% specificity, 100% positive predictive value, and 98% negative predictive value. Our conclusions are that serial antepartum ultrasound examination of twins for congenital anomalies in our institution is very specific, with high positive and negative predictive values. The sensitivity, while also excellent, has limitations, which should be discussed with the patient.

We retrospectively evaluated relapse of medulloblastoma after low- or high-dose craniospinal radiotherapy, and after conventional or hyperfractionated posterior fossa irradiation.Ninety-two pediatric patients were treated postoperatively since 1970 at the University of California, San Francisco. Until 1989, we employed conventional fractionation with low (or = 30 Gy) or high-dose craniospinal fields and low-dose (or = 56 Gy) posterior fossa boosts. Recently, hyperfractionation delivered low- or high-dose to the craniospinal axis and high-dose to the posterior fossa. Most patients treated after 1979 received chemotherapy.Median follow-up was 70 months. Five-year disease-free survival was 36% (22% for poor-risk vs. 59% for good-risk patients). Five-year overall survival was 52% (43% for poor vs. 68% for good-risk). Neither the dose to the posterior fossa nor the craniospinal axis was statistically related to recurrence. Failure in the posterior fossa occurred despite boosts greater than 56 Gy. Females, over the age of 6 years, had significantly better relapse-free survival than males of the same age. Six of the 54 patients who relapsed were long-term survivors.Low-dose craniospinal radiotherapy, where the majority of patients received chemotherapy, was not associated with increased failure. High-dose posterior fossa hyperfractionation did not improve control. Long-term survival was noted in a number of patients after relapse. We recommend 60 Gy or greater with conventional fractions to the primary area, and continued study of low-dose craniospinal irradiation with adjuvant chemotherapy.

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.

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, p0.005, and 28 versus 53 percent, p0.001, 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, p0.01). 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, p0.01), 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.

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)

Physical features do not reliably distinguish premature infants with bacterial infections from those with noninfectious conditions. We evaluated the association of depressed plasma fibronectin with sepsis among hospitalized very low birth weight infants (1500 gm). Reference values were determined by sequential plasma sampling from 60 healthy very low birth weight infants. Among 17 very low birth weight infants with proved late-onset sepsis (mean age, 20 days; range, 10 to 42 days), 9 had plasma fibronectin levels more than 1 SD below the age- and birth weight-associated mean. Overall, the sensitivity and specificity of the finding of depressed fibronectin levels were 53% and 94%, respectively. These data suggest that depression of plasma fibronectin occurs commonly in association with late-onset sepsis among hospitalized premature infants.

Tissue diagnosis is necessary for optimal treatment of pineal region tumors in children. Preoperative staging should include craniospinal MR imaging with and without gadolinium DTPA enhancement, CSF sampling for cytology, and measurement of biologic tumor markers in serum and CSF. Surgical approach is determined by results of preoperative MR imaging and the extent of resection by the results of staging and intraoperative frozen-section histopathologic evaluation. There is no longer a role for the radiation test dose (2000 cGy) in the management of these tumors. Postoperative treatment is based on histopathology and extent of disease. Benign tumors are treated with surgery only, and nondisseminating focal tumors with surgery and focal radiation therapy. Non-germinoma malignant germ cell tumors are best treated with neoadjuvant chemotherapy followed by radiation therapy given focally for focal disease; craniospinal radiation therapy is reserved for patients with evidence of disseminated disease at the completion of induction chemotherapy.

Cell kinetics and clinical behavior were correlated for 22 primary and 10 recurrent or metastatic medulloblastomas from 30 patients.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.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.A high LI may reflect rapid medulloblastoma growth, but survival seemed more dependent on sensitivity to radiation therapy.

Gardnerella vaginitis is one of the most common diagnoses in our outpatient clinic. From January 1, 1989 through July 30, 1989 we had 230 positive cultures for G. vaginitis. Eighty-three compliant patients in this group had unabated symptoms with documented positive cultures for Gardnerella after treatment with metronidazole. This led to the use of alternative regimens of ceftriaxone or clindamycin. A survey of antibiotic choice and post-treatment culture obtained 103 entries from 34 active duty women soldiers and 60 women dependents. This paper presents the results of the survey after an introduction beginning with a 1953 article in U.S. Armed Forces Medical Journal.

The MR studies of seven pediatric patients with surgically proved spinal dorsal dermal sinuses were reviewed retrospectively. Five of the seven had associated congenital tumors (three epidermoids, two dermoids). The subcutaneous portions of the spinal tracts and intramedullary portions of tumor were easily identified with the use of standard spin-echo techniques. However, except for limited areas where they were lined by fat, the intraspinal portions of the dermal sinuses were poorly seen. Moreover, diffuse subarachnoid tumor was missed in two patients. Three-dimensional Fourier transform gradient-echo acquisition using a volumetric radiofrequency pulse as a "spoiler" proved to be helpful in evaluating these abnormalities. Optimal radiologic workup of patients with dorsal dermal sinuses awaits the development of new MR imaging sequences. For now, heavily T1-weighted MR sequences should be obtained and supplemented with sonography in infants and with CT myelography in older children.

Seven patients with symptomatic aneurysms involving the petrous segment of the internal carotid artery were treated by endovascular techniques (six patients) or surgical ligation (one patient). Patients' ages at the time of treatment ranged from 7 to 62 years (mean, 30 years). The presenting symptoms were pain (seven patients), eighth nerve dysfunction (three patients), seventh nerve dysfunction (one patient), fifth nerve dysfunction (two patients), and bruit (one patient). Two patients, ages 7 and 19, respectively, presented with giant, partially thrombosed petrous aneurysms and had hemiatrophy of the body ipsilateral to the side of the aneurysm. Only one patient had a history of trauma; aneurysms in the remaining patients were presumed to be congenital in origin. In one patient with a saccular aneurysm, a balloon could be navigated into the aneurysm, obliterating it but preserving the parent artery. The remaining six patients had fusiform aneurysms with intraluminal thrombus and underwent proximal occlusion (four patients) or trapping procedure (two patients). In all patients, symptoms were alleviated after thrombosis of the aneurysm. The only complication was a transient visual loss in a hypercoagulable patient, occurring after carotid occlusion. Petrous carotid aneurysms can produce a wide clinical spectrum of signs and symptoms in younger patients; these aneurysms frequently are fusiform and contain chronic thrombus. They can be treated effectively by endovascular or surgical occlusive procedures.