Use of "<Emphasis Type="Italic">biokit</Emphasis>HSV-2 Rapid Assay" to improve the positive predictive value of Focus HerpeSelect HSV-2 ELISA

Background  

Commercially available assays to detect antibodies to the herpes simplex virus type 2 (HSV-2)-specific glycoprotein gG-2 have markedly improved serologic diagnosis of HSV-2 infection. However, even tests with high specificity can have low positive predictive values in low prevalence populations. HSV-2 is a chronic, life-long viral infection that requires both medical attention and potential alterations in health care strategy. As such, the concern for false positive diagnoses is high confirmatory testing is routine for other viral serologies such as HIV and hepatitis C. We evaluated such a strategy for HSV-2 serology by using an easily performed commercial test, biokitHSV-2 rapid test ("Biokit"; Biokit USA, Lexington MA) as a confirmatory test for the widely used gG-2 specific serology ("Focus;" HerpeSelect HSV-2 ELISA; Focus Diagnostics, Cypress CA).     

Identification of a novel splice site mutation in the human hairless gene underlying atrichia with papular lesions

Atrichia with Papular Lesions (APL) is a rare autosomal recessive disorder characterized by complete hair loss that begins shortly after birth with the development of papular lesions on various regions of the body. Since the establishment of hairless (HR) gene mutations as the cause of this disorder, several patients previously assumed to suffer from alopecia universalis have been subsequently diagnosed with APL. In this study we have identified a novel splicing mutation, IVS8+2T-->G, in the hairless gene. This mutation most likely abolishes normal splicing of exon 8 and potentially leads to out-of-frame skipping of this exon and a downstream premature termination codon (PTC). Our findings contribute to the growing body of HR mutations implicated in APL and provide further evidence for the differentiation of APL from alopecia universalis.     

Serotype distribution and antimicrobial susceptibility of <Emphasis Type="Italic"> Streptococcus pneumoniae </Emphasis>causing invasive infections and acute otitis media in children

A prospective study was conducted to determine the serotypes and antibiotic resistance patterns of pneumococcal isolates from children with invasive pneumococcal disease (IPD) and acute otitis media (AOM). From October 2001 to May 2002, 65 children with IPD (28 bacteraemic pneumonia, 24 bacteraemia without focus, 7 meningitis, 6 other infections) and 78 with AOM were identified. The most common serotypes causing IPD were 14 (32.3%), 6B (20.0%), 1 (18.5%) and 19F (7.7%) whereas the predominant serotypes causing AOM were 19F (35.9%), 14 (16.7%) and 23F (9.1%). Sixty-nine percent of IPD and 70.5% of AOM were caused by vaccine serotypes. The vaccine serotypes were more commonly encountered in meningitis cases and in children younger than 2 years of age. Intermediate resistance to penicillin was observed in 6 of 65 (9.2%) IPD isolates, one of which was intermediately resistant to cefotaxime (1.6%), whereas none exhibited high-level resistance to penicillin or other beta-lactam antibiotics. A higher proportion of antimicrobial resistance was noted in AOM isolates; 29 of 78 (37.4%) exhibited intermediate resistance and 8 (10.2%) high level resistance to penicillin, four of which had intermediate resistance to cefotaxime. Significant resistance was also noted to erythromycin; 38.5% of IPD and 48.7% of AOM isolates were resistant. Multidrug resistance was observed in one IPD and in eight AOM isolates. Conclusion:these findings have implications in the potential use of 7-valent conjugate vaccine in our region.Abbreviations AOM acute otitis media - IPD invasive pneumococcal disease - MIC minimal inhibitory concentration     

Obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas

OBJECTIVE: To determine the rate, obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas. STUDY DESIGN: A population-based study comparing all singleton deliveries between the years 1988 and 1999 in women with and without uterine leiomyomas was performed. Patients lacking prenatal care were excluded from the analysis. Multivariable analysis, adjusting for possible confounders, such as maternal age, parity and gestational age, was performed to investigate associations between uterine leiomyomas and selected outcomes. RESULTS: There were 105,909 singleton deliveries with 690 (0.65%) complicated by uterine leiomyomas during the study period. Using a multivariable analysis, the following conditions were significantly associated with uterine leiomyomas: nulliparity (odds ratio [OR]=4.0, 95% confidence interval [CI] 3.3-4.7, P<.001), chronic hypertension (OR=1.9, 95% CI 1.6-2.4, P<.001), hydramnios (OR=1.5, 95% CI 1.2-2.0, P<.001), diabetes mellitus (OR=1.4, 95% CI 1.1-1.7, P=.001) and advanced maternal age (OR=1.2, 95% CI 1.1-1.2, P<.001). Higher rates of perinatal mortality (2.2% vs. 1.2%, OR=1.8, 95% CI 1.1-3.2, P<.001) were found in the uterine leiomyoma group as compared to the control group. While adjusting for maternal age, parity, gestational age and malpresentation, pregnancies with uterine leiomyomas had higher rates of cesarean deliveries (OR=6.7, 95% CI 5.5-8.1, P<.001), placental abruption (OR=2.6, 95% CI 1.6-4.2, P<.001) and preterm deliveries (<36 weeks' gestation, OR=1.4, 95% CI 1.1-1.7, P=.009) as compared to pregnancies without uterine leiomyomas. Conversely, no significant differences were noted regarding perinatal mortality (OR=1.4, 95% CI 0.7-2.8, P=.351) after controlling for maternal age, parity and gestational age using a multivariable analysis. CONCLUSION: Uterine leiomyomas increase the risk of adverse pregnancy outcomes, thus emphasizing the importance of appropriate intrapartum management of these high-risk pregnancies.     

How medical students define surgical mentors

BACKGROUND: Current literature does not define ideal qualities of surgical mentors. We sought to define mentoring qualities desired by medical students in attending and resident surgeons. METHODS: We conducted a survey asking third-year medical students to identify the best attending surgeon and resident surgeon mentors during their surgical clerkship and to explain their selections. Comments were systematically evaluated using content analysis. RESULTS: The survey response rate was 94.8%. Attending surgeon mentors were described by 84 students; 70 students described resident surgeon mentors. Students most frequently described the "teacher" role for attending surgeons. For resident surgeon mentors, students most often ranked the "person" role. Students prioritized characteristics or attributes within roles differently for attending and resident surgeon mentors. CONCLUSIONS: Medical students' expectations of attending and resident surgeon mentors differ. Emphasis on behaviors consonant with identified characteristics may improve mentoring of medical students by surgeons and increase interest in surgical careers.     

Resource utilization and its management in splenic trauma

Background

This study compared resource utilization and its management for splenic injury at 2 level-I trauma centers and a pediatric referral center with other facilities in a state currently developing a trauma system.

Methods

Management strategy, length of stay, and total charges for children were compared among the pediatric referral center, trauma centers, and other facilities. Adult management, length of stay, and total charges were compared between trauma centers and other facilities.

Results

Nonoperative management was more frequent in children at the pediatric referral center than trauma centers or other facilities and was more common in adults at trauma centers than at other facilities. Mean length of stay and total charges for children were significantly greater at the pediatric referral center and trauma centers than at other facilities and for adults at trauma centers than at other facilities. Facility type was associated with length of stay and total charges when injury type and severity were controlled.

Conclusions

Nonoperative management of splenic injury is more common at trauma centers, and splenic trauma management may be more costly at trauma centers.     

Conservative management of hyperplastic and multicentric nephroblastomatosis

PURPOSE: The treatment of hyperplastic nephroblastomatosis remains controversial. We report the advantages of conservative management of hyperplastic and multicentric nephroblastomatosis associated with unilateral Wilms tumor (WT). MATERIALS AND METHODS: During the last 10 years 48 children with unilateral WT were consecutively treated at our 2 institutions. Children with multiple solid renal masses on imaging were treated with 2-drug chemotherapy until disappearance of the lesions. Stabilization or progression of the lesions despite chemotherapy, as well as heterogeneity of the lesions on imaging, prompted nephron sparing surgery (NSS). RESULTS: Three female infants (12, 13 and 20 months old, respectively) presented with multiple solid renal tumors at imaging. Despite chemotherapy, small and unilateral WT developed in 2 cases of hyperplastic nephroblastomatosis, which was excised. One of these infants subsequently presented with a small contralateral metachronous WT, which was excised. Both infants are disease-free with 2 normal kidneys at followup of 6 and 2 years, respectively. The third infant, who presented with unilateral multicentric WT and unilateral hyperplastic nephroblastomatosis nodules, was successfully treated with preoperative chemotherapy and enucleation of 5 tumors. Subsequently, nephrectomy was performed at another institution because the abnormal kidney outline due to NSS was misinterpreted as a recurrence of WT. She was lost to followup. CONCLUSIONS: Hyperplastic and multicentric nephroblastomatosis is not a rare lesion and is most often associated, either initially or subsequently, with WT. In some infants with multiple solid renal masses on imaging chemotherapy and for developing WT NSS may safely allow maximum sparing of the parenchyma of both kidneys.     

Fine-needle cytology and flow cytometry immunophenotyping and subclassification of non-Hodgkin lymphoma: a critical review of 307 cases with technical suggestions

BACKGROUND: Flow cytometry (FC) is a useful adjunct to fine-needle aspiration cytology (FNC) in evaluating lymphoproliferative disorders. The authors present a critical review of 307 lymph nodal and extra lymph nodal lymphoproliferative disorders that were diagnosed with FNC and FC. METHODS: FC was performed over a 4-year period on 185 palpable and 122 impalpable lymph nodal and extra lymph nodal lymphoproliferative processes under ultrasound or computed tomography guidance. FC was performed using the following fluoresceinated antibodies: CD3, CD4/CD8, CD2/CD7/CD3, CD5/CD10/CD19, CD19/kappa/lambda, FMC7/CD23/CD19, CD38/CD56/CD19, and bcl-2. The series included 15 inadequate, 10 suspicious, and 135 benign reactive hyperplasias (BRHs); 70 primary non-Hodgkin lymphomas (NHLs), and 77 recurrent NHLs (rNHLs). FC/FNC diagnoses of suspicious, NHL, and rNHL were controlled either histologically or clinically or by the interphase fluorescence in situ hybridization demonstration of t(11;14)(q13;q32) in two cases of mantle cell lymphoma. BRHs were controlled by follow-up. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the FC/FNC diagnoses of NHL, rNHL, and BRH were calculated as well as the identification of specific subtypes among the small- and medium-sized cells. RESULTS: Statistical analysis showed 93% sensitivity, 100% specificity, 100% PPV, and 91% NPV in NHL, rNHL, and BRH discrimination. The subclassification of small cell and medium-sized NHLs showed 63% sensitivity, 88% specificity, 95% PPV, and 37% NPV. CONCLUSIONS: FC applied to FNC enhanced the precision of cytologic diagnosis in lymph nodal and extra lymph nodal lymphoproliferative disorders and allowed further subclassification in more than half of the cases, thus avoiding invasive surgical biopsies in many patients.     

The neutrophil, not the tumor: serum CA 15-3 elevation as a result of granulocyte--colony-stimulating factor-induced neutrophil MU1C overexpression and neutrophilia in patients with breast carcinoma receiving adjuvant chemotherapy

BACKGROUND: Patients with resected breast carcinoma who received granulocyte-colony-stimulating factor (G-CSF)-supported adjuvant chemotherapy exhibited an increase in their serum CA 15-3 levels. The authors investigated the role of G-CSF-induced neutrophil MUC1 expression in this setting. METHODS: Twenty-two patients with resected early breast carcinoma and 6 patients with high-grade lymphoma received chemotherapy cycles with or without G-CSF support. When given, G-CSF was administered for either 5 or 10 days per cycle. Immunocytochemical staining and flow cytometric analysis of peripheral blood neutrophils and bone marrow myeloid cells for MUC1 epitopes were performed during treatment. RESULTS: At baseline, the median serum CA 15-3 was 16 U/mL, with weak MUC1 expression in peripheral neutrophils (median immunocytochemical score [ICCS] = 40, flow cytometric score [FCS] = 211 antibody molecules per neutrophil). For patients receiving chemotherapy cycles with 5-day G-CSF support, median CA 15-3 levels increased moderately (median = 28 U/mL; P = 0.016) and absolute neutrophil counts (ANC) did not increase, whereas ICC staining showed a moderate increase (median ICCS = 105; P = 0.015). For patients receiving chemotherapy cycles with 10-day G-CSF, serum CA 15-3 levels increased 2-4-fold from baseline levels and reached abnormal levels (median = 47; P < 0.0005) and the ANC increased (median = 21,400/mm(3); P = 0.007), whereas significant induction of MUC1 expression occurred in the cell membrane and mostly in the cytoplasm of neutrophils (median ICCS = 162; P = 0.001). Flow cytometry detected increased cytoplasmic, but not surface, neutrophil MUC1 expression in the 10-day G-CSF group only (baseline median FCS = 3975, 4th cycle median = 6327 molecules per cell; P = 0.028). In the bone marrow, induction of MUC1 expression was observed in the 10-day G-CSF group only in band forms and neutrophils, but not in more immature myeloid cells. Serum CA 15-3 levels and ICC score were found to demonstrate a linear relation. When ICCS and ANC were incorporated in a combined score, its relation with serum CA 15-3 levels demonstrated a parabolic (cubic) pattern. Serum CA 15-3 levels, ANC, and neutrophil MUC1 staining returned to baseline after the completion of therapy. No excess of malignant recurrences were observed. CONCLUSIONS: Women with resected breast carcinoma who received G-CSF-primed chemotherapy showed serum CA 15-3 elevation due to an increase in peripheral blood neutrophil number and induced neutrophil cytoplasmic MUC1 expression, which was caused by G-CSF. Physicians should be aware of this interaction.     

Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells

The cytotoxic effects of asbestos are partly mediated by the production of free radicals, including nitric oxide (NO). SV40 has been suggested to synergize with asbestos in the pathogenesis of malignant mesothelioma. Crocidolite asbestos fibers induced in human mesothelial and malignant mesothelioma cells a significant increase of NO synthase activity and expression, which was absent in SV40-infected cells. Furthermore, SV40 infection prevented the NF kappa B activation elicited by crocidolite in both mesothelial and mesothelioma cells. These data suggest that SV40, by inhibiting the synthesis of NO, could favor the survival of transformed, potentially neoplastic cells.