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Background and Purpose: Successful outcomes from bacterial meningitis require rapid antibiotic treatment; however, unnecessary treatment of viral meningitis may lead to increased toxicities and expense. Thus, improved diagnostics are required to maximize treatment and minimize side effects and cost. Thirteen clinical decision rules have been reported to identify bacterial from viral meningitis. However, few rules have been tested and compared in a single study, while several rules are yet to be tested by independent researchers or in pediatric populations. Thus, simultaneous test and comparison of these rules are required to enable clinicians to select an optimal diagnostic rule for bacterial meningitis in settings and populations similar to ours., Methods: A retrospective cross-sectional study was conducted at the Infectious Department of Pediatric Hospital Number 1, Ho Chi Minh City, Vietnam. The performance of the clinical rules was evaluated by area under a receiver operating characteristic curve (ROC-AUC) using the method of DeLong and McNemar test for specificity comparison., Results: Our study included 129 patients, of whom 80 had bacterial meningitis and 49 had presumed viral meningitis. Spanos's rule had the highest AUC at 0.938 but was not significantly greater than other rules. No rule provided 100% sensitivity with a specificity higher than 50%. Based on our calculation of theoretical sensitivity and specificity, we suggest that a perfect rule requires at least four independent variables that posses both sensitivity and specificity higher than 85-90%., Conclusions: No clinical decision rules provided an acceptable specificity (>50%) with 100% sensitivity when applying our data set in children. More studies in Vietnam and developing countries are required to develop and/or validate clinical rules and more very good biomarkers are required to develop such a perfect rule.

Background: Several population-wide HIV-1 subtype distribution studies in Uganda have evaluated relatively healthy clinic patients. Given the differences in HIV-1 disease progression based on subtype, we examined HIV-1 subtype distribution and disease outcomes among hospitalized patients with severe sepsis., Methods: Patients with severe sepsis were enrolled at two hospitals in Uganda. Data collected included demographics, Karnofsky scores, highly active antiretroviral therapy (HAART) use, HIV-1 serostatus, CD4+ T cell concentration, whole blood lactate concentration, and blood cultures. HIV-1 subtypes were determined by sequencing parts of the gag and env genes, followed by phylogenetic analysis., Results: Of the 267 patients evaluated, 228 (85.4%) were HIV infected. The predominant HIV-1 subtypes were A (46%), D (17%), and AD recombinants (30%). HIV-1 subtypes B, C, and other recombinants were uncommon. Patients infected with HIV-1 subtypes A, D and AD viruses were similar in demographics, CD4(+) T cell concentration, HAART use, Karnofsky scores, whole blood lactate concentration, and positive blood cultures. There was no difference in 30-day mortality from severe sepsis between the 3 groups (p = 0.99)., Conclusion: A high proportion of HIV-1 subtypes A and AD recombinants was observed in this cohort of severely septic patients. The proportion of AD recombinants was higher in this cohort than in previous cohorts of Ugandan HIV-1 patients. No difference in baseline demographics, clinical factors or 30-day mortality was seen across HIV-subtypes.

It is evident that valvular surgeries have made countless advances since the first valve surgery in 1925 when Dr Henry Souttar operated on a woman with mitral stenosis. Patients in the 21st century have a better chance of surviving as a result of these advances. In addition to providing high-quality health care to patients, educating patients and their families regarding the disease processes, symptoms, diagnosis, types of valve surgeries, different approaches, complications, nonsurgical care, recovery, and lifestyle changes is an instrumental component to a successful recovery.

Objective: To assess outcomes in managing primary lentigo maligna through surgical excision, radiation therapy, and carbon dioxide laser ablation., Methods: Retrospective case series review of all patients with primary lentigo maligna diagnosed and treated in London, Ontario, Canada, between July 2, 1991, and June 29, 2010., Results: Seventy-five patients aged 39 to 93 years (mean age, 64.8 years) were included in the study; 73 patients chose treatment. Twenty-seven patients were treated with surgical excision, 31 patients with radiation therapy, and 15 patients with carbon dioxide laser ablation. The median follow-up times were 16.6 months for surgical excision, 46.3 months for radiation therapy, and 77.8 months for carbon dioxide laser ablation (P < .001). Recurrence rates by treatment modality were 4.2% (1 of 27) for surgical excision, 29.0% (9 of 31) for radiation therapy, and 6.7% (1 of 15) for carbon dioxide laser ablation., Conclusions: A trend toward lower recurrence rates with surgical excision and carbon dioxide laser ablation was identified, but the results were not statistically significant. Carbon dioxide laser ablation may have a role as an alternative treatment for lentigo maligna among patients in whom standard treatments, such as surgical excision and radiation therapy, are declined or carry significant morbidity.

Activated protein C (aPC) promotes fibrinolysis while inhibiting coagulation and inflammation. In septic patients, aPC levels are depleted, and aPC treatment has emerged as a therapeutic option. To better understand the mechanism(s) by which aPC improves survival in sepsis, we sought to determine the effect of aPC treatment on hepatic vasoactive gene and protein expression, leading to changes in hepatic vascular responsiveness in a septic animal model. Under anesthesia, rats underwent sham or cecal ligation and puncture followed by aPC treatment (1 mg/kg, twice daily, i.v.). Treatment with aPC significantly decreased hepatic endothelin 1 (ET-1)/ET A receptor mRNA and protein expression. To determine the effect of aPC on hepatic microvasculature, ET-1-induced changes in liver microcirculation were assessed by intravital microscopy. This approach demonstrated aPC significantly improved hepatic perfusion index in the animals that underwent cecal ligation and puncture in the absence of significant changes in portal venous pressure. Furthermore, although aPC did not affect ET-1-dependent sinusoidal vasoconstriction, aPC induced hepatoprotective effects via enhanced red blood cell velocity. Collectively, these data demonstrate aPC ameliorates ET-1-dependent changes in hepatic microcirculation and improves hepatic function in the setting of sepsis.

We evaluated the association between severity of sepsis and in-hospital mortality in 150 patients with non-surgical sepsis at a regional referral hospital in Uganda. In-hospital mortality occurred in 5 of 52 (9.6%) patients with sepsis, 24 of 71 (33.8%) patients with severe sepsis, and 16 of 27 (59.3%) patients with septic shock. In the multivariate analysis, the identification of severe sepsis (adjusted hazard ratio [AHR] = 2.9, 95% confidence interval [CI] = 1.0-8.2, P = 0.04), septic shock (AHR = 5.7, 95% CI = 1.6-20.3, P = 0.007), and dysfunction of three or more organs (AHR = 2.9, 95% CI = 1.1-7.3, P = 0.03) increased the risk of in-hospital mortality. Adding aggregate organ dysfunction to the multivariate equation that included the sepsis category statistically significantly improved the model, but the opposite did not. Predictors of mortality were easily measurable and could be used to risk stratify critically ill patients in resource-constrained settings.

Aim: To identify and characterize the function of nonmuscle myosin II (NMM II) isoforms in primary rat hepatic stellate cells (HSCs)., Methods: Primary HSCs were isolated from male Sprague-Dawley rats by pronase/collagenase digestion. Total RNA and protein were harvested from quiescent and culture-activated HSCs. NMM II isoform (II-A, II-B and II-C) gene and protein expression were measured by RealTime polymerase chain reaction and Western blot analyses respectively. NMM II protein localization was visualized in vitro using immunocytochemical analysis. For in vivo assessment, liver tissue was harvested from bile duct-ligated (BDL) rats and NMM IIisoform expression determined by immunohistochemistry. Using a selective myosin II inhibitor and siRNA-mediated knockdown of each isoform, NMM II functionality in primary rat HSCs was determined by contraction and migration assays., Results: NMM II-A and II-B mRNA expression was increased in culture-activated HSCs (Day 14) with significant increases seen in all pair-wise comparisons (II-A: 12.67 ± 0.99 (quiescent) vs 17.36 ± 0.78 (Day 14), P < 0.05; II-B: 4.94 ± 0.62 (quiescent) vs 13.90 ±0.85 (Day 14), P < 0.001). Protein expression exhibited similar expression patterns (II-A: 1.87 ± 2.50 (quiescent) vs 58.64 ± 8.76 (Day 14), P < 0.05; II-B: 1.17 ± 1.93 (quiescent) vs 103.71 ± 21.73 (Day 14), P < 0.05). No significant differences were observed in NMM II-C mRNA and protein expression between quiescent and activated HSCs. In culture-activated HSCs, NMM II-A and II-B merged with F-actin at the cellular periphery and throughout cytoplasm respectively. In vitro studies showed increased expression of NMM II-B in HSCs activated by BDL compared to sham-operated animals. There were no apparent increases of NMM II-A and II-C protein expression in HSCs during hepatic BDL injury. To determine the contribution of NMM II-A and II-B to migration and contraction, NMM II-A and II-B expression were downregulated with siRNA. NMM II-A and/or II-B siRNA inhibited HSC migration by approximately 25% compared to scramble siRNA-treated cells. Conversely, siRNA-mediated NMM II-A and II-B inhibition had no significant effect on HSC contraction; however, contraction was inhibited with the myosin II inhibitor, blebbistatin (38.7% ± 1.9%)., Conclusion: Increased expression of NMM II-A and II-B regulates HSC migration, while other myosin IIclasses likely modulate contraction, contributing to development and severity of liver fibrosis.

Background: Activated protein C (aPC) confers survival benefit in patients with sepsis, yet its protective mechanism(s) remain unclear. Herein, we determined time-dependent severity of renal dysfunction during polymicrobial sepsis. We hypothesized aPC restores renal function by preserving organ architecture and reducing inflammation., Materials and Methods: Sprague-Dawley rats underwent sham operation or cecal ligation and puncture (CLP). At 6 or 24 h post-surgery, kidney function was assessed by plasma electrolytes, blood urea nitrogen (BUN), and creatinine levels. Renal architecture was examined histologically. In the next series of experiments, 24-h post-surgery, animals were treated with vehicle or aPC (1 mg/kg) for 4 d, and kidney function and circulating cytokine levels were measured. Plasma was collected and assayed for BUN, creatinine, and lactate dehydrogenase (LDH) levels. Serum cytokine levels were measured by ELISA., Results: Plasma electrolytes, BUN, creatinine, and renal architecture were altered 6 h after CLP. Treatment with aPC significantly inhibited sepsis-induced elevations in BUN, creatinine, LDH levels, and improved renal architecture. After CLP, interferon gamma (INFγ) decreased, while interleukins-1beta and -10 (IL-1β and IL-10) increased; these effects were attenuated by aPC treatment., Conclusions: Our data demonstrate that renal dysfunction occurs as early as 6 h following sepsis and continues thereafter. Treatment with aPC attenuated INFγ and IL-1β changes, and preserved renal function in sepsis. These data suggest aPC may confer a survival advantage by reducing systemic inflammation and, in doing so, preserving organ function., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Hepatic fibrosis is characterized by excess type I collagen deposition and exacerbated inflammatory response. Naltrexone, an opioid receptor antagonist used for treating alcohol abuse, attenuates hepatocellular injury in fibrotic animal models, which can be accompanied by deleterious side effects. Additionally, opioid neurotransmission is upregulated in patients with inflammatory liver disease. Several derivatives of Naltrexone, Nalmefene (Nal) and JKB-119, exert immunomodulatory activity; however, unlike Nal, JKB-119 does not show significant opioid receptor antagonism. To delineate the potential hepatoprotective effects of these compounds, we investigated if JKB-119 and Nal could modulate activation of hepatic stellate cells (HSCs), primary effector cells that secrete type I collagen and inflammatory mediators during liver injury. Our results demonstrated that Nal or JKB-119 treatment decreased smooth muscle α-actin, a marker of HSC activation, mRNA and protein expression. Despite decreased collagen mRNA expression, both compounds increased intracellular collagen protein expression; however, inhibition of collagen secretion was observed. To address a possible mechanism for suppressed collagen secretion or retention of intracellular collagen, endoplasmic (ER) protein expression and matrix metalloproteinase (MMP) activity were examined. While no change in ER protein expression (Grp78, PDI, Hsp47) was observed, MMP13 mRNA expression was dramatically increased. In an acute LPS inflammatory injury animal model, JKB-119 treatment decreased liver injury (ALT), plasma TNFα and PMN liver infiltration. Overall, these results suggest that JKB-119 can directly inhibit HSC activation attributed to anti-inflammatory activity and may, therefore, attenuate inflammation associated with HSC activation and liver disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Topical photodynamic therapy (PDT) is a successful treatment for nonmelanotic skin cancers (NMSCs). Nevertheless, surgical excision continues to be the gold standard treatment. Cervicofacial excision often results in functional and aesthetic impairment. We hypothesize that topical PDT as a neoadjuvant therapy to surgical excision may reduce tumour size and subsequently decrease local morbidity., Objective: To determine the utility of PDT in reducing the NMSC area for the purpose of surgical excision., Method: A prospective cohort study., Results: Thirty-three basal cell carcinomas with a mean area of 523.11 ± 120.93 mm² and 26 squamous cell carcinomas with a mean area of 357.53 ± 61.96 mm² were included. Of these lesions, 22 demonstrated a complete curative response after an average of two PDT treatments, which were then confirmed with histologically negative biopsies. The remaining lesions demonstrated a partial response to topical PDT with a maximum reduction in lesion area following an average of three PDT treatments of at least 88% (p < .05). These lesions were then excised with clear histologic margins. Follow-up at 1 year for all lesions demonstrated no locoregional recurrence., Conclusions: This is the first study to investigate the efficacy of neoadjuvant topical PDT in the management of NMSC. The results suggest that for NMSC not demonstrating a complete curative response to PDT, neoadjuvant PDT can substantially reduce tumour burden, allowing for less morbid surgical excisions with histologically clear margins.

Background. This preliminary study sought to determine the success of photodynamic therapy (PDT) in reducing lesion size in an effort to assess the potential application of this treatment approach in a neoadjuvant role. Objectives. To quantify the effects of PDT on lesion area (mm(2)) for basal cell and squamous cell carcinomas of the face. Results. Eighteen participants (10 BCC lesions and 8 SCC lesions of the face) were assessed. Four lesions (all from the BCC group) showed a complete response to PDT. Of the remaining 14 lesions, 85.7% (n = 12) showed reductions in lesion area, while two lesions showed increase in lesion area. Proportional reductions for the 12 lesions that did not demonstrate complete response or an increase in area following-PDT were found to range from 13.2% to 85.1% (BCC) and 6.7% to 89.7% (SCC). Conclusions. PDT as a neoadjuvant treatment may provide a simple, efficient, and viable approach to reducing the area of malignant lesions of the face with the advantage of reduced cosmetic and aesthetic morbidities.

Aim: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation., Methods: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor., Results: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR., Conclusion: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation.

A double triangular flap, or hatchet flap, with a partial cutaneous pedicle, has great versatility for facial reconstruction, yet there has been little published discussion regarding the potential applications and/or modifications of the flap. A total of 483 cutaneous malignant neoplasms have been excised and repaired by the senior author (C.C.M.) using a modified bilateral hatchet flap; 366 of the neoplasms were located in the head and neck region. The flap has been used to reconstruct defects in the scalp, eyebrow, lower eyelid, nasal tip, cheek, chin, arms, and torso, with no cases of flap loss. The design of the flap and our modification will be discussed in detail, along with a description of 4 representative cases.

Background: Sepsis likely contributes to the high burden of infectious disease morbidity and mortality in low income countries. Data regarding sepsis management in sub-Saharan Africa are limited. We conducted a prospective observational study reporting the management and outcomes of severely septic patients in two Ugandan hospitals. We describe their epidemiology, management, and clinical correlates for mortality., Methodology/results: Three-hundred eighty-two patients fulfilled enrollment criteria for a severe sepsis syndrome. Vital signs, management and laboratory results were recorded. Outcomes measured included in-hospital and post-discharge mortality. Most patients were HIV-infected (320/377, 84.9%) with a median CD4+ T cell (CD4) count of 52 cells/mm(3) (IQR, 16-131 cells/mm(3)). Overall mortality was 43.0%, with 23.7% in-hospital mortality (90/380) and 22.3% post-discharge mortality (55/247). Significant predictors of in-hospital mortality included admission Glasgow Coma Scale and Karnofsky Performance Scale (KPS), tachypnea, leukocytosis and thrombocytopenia. Discharge KPS and early fluid resuscitation were significant predictors of post-discharge mortality. Among HIV-infected patients, CD4 count was a significant predictor of post-discharge mortality. Median volume of fluid resuscitation within the first 6 hours of presentation was 500 mLs (IQR 250-1000 mls). Fifty-two different empiric antibacterial regimens were used during the study. Bacteremic patients were more likely to die in hospital than non-bacteremic patients (OR 1.83, 95% CI = 1.01-3.33). Patients with Mycobacterium tuberculosis (MTB) bacteremia (25/249) had higher in-hospital mortality (OR 1.97, 95% CI = 1.19-327) and lower median CD4 counts (p = 0.001) than patients without MTB bacteremia., Conclusion: Patients presenting with sepsis syndromes to two Ugandan hospitals had late stage HIV infection and high mortality. Bacteremia, especially from MTB, was associated with increased in-hospital mortality. Most clinical predictors of in-hospital mortality were easily measurable and can be used for triaging patients in resource-constrained settings. Procurement of low cost and high impact treatments like intravenous fluids and empiric antibiotics may help decrease sepsis-associated mortality in resource-constrained settings.

Two HIV-1 infected patients developed signs and symptoms consistent with adrenal suppression after being exposed to intra-articular triamcinolone acetate while also receiving ritonavir as part of their highly active antiretroviral therapy. Laboratory evaluation confirmed secondary adrenal suppression in both cases. Both patients recovered without the need for chronic replacement steroids. Adrenal suppression has been described as an adverse outcome in patients treated with fluticasone and concomitant ritonavir. In the reported cases, the adrenal suppression likely developed as a result of increased systemic concentrations of triamcinolone due to an inhibition of cytochrome p450 3A4 metabolism. Practitioners of HIV medicine should be aware of the potential negative interaction of injected triamcinolone and ritonavir.

Objectives/hypothesis: To determine the efficacy of interventions to improve and monitor skin scarring, a valid assessment instrument must be used. Current tools used for the evaluation of skin scarring employ equal appearing interval (EAI) scales that assume scar dimensions conform to linear models. Some scar features meet these assumptions, whereas others may not be accurately described. This study determined if current methods of scar evaluation validly characterize inherent features of scars, and in doing so, empirically validate if specific scar dimensions were best represented by linear or nonlinear mathematical models., Study Design: Prospective, randomized, cross-over trial., Methods: Twenty-seven observers evaluated 30 scar photos utilizing both EAI and direct magnitude estimation (DME) scaling methods. The method of scaling and the assessed dimensions of vascularity, pigmentation, thickness, pliability, and surface area were randomized. EAI and DME data were evaluated to identify whether each scar dimension conformed to linear or curvilinear mathematical models., Results: Best-fit analysis revealed the dimensions of vascularity and pigmentation to be more accurately described using curvilinear functions, whereas pliability, thickness and surface area were best defined using linear models., Conclusions: The scar dimension under assessment must be considered when attempting to validly apply an assessment instrument. Several commonly evaluated dimensions of skin scarring are not appropriately characterized using linear EAI scales. Thus, present assessment instruments must be revised to account for this aberration to allow for a valid means of objectively evaluating skin scarring.

We enrolled 382 patients at two hospitals in Uganda in a prospective observational study of severe sepsis. Because artemisinins improve survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with negative malaria smears (N = 328 of 379), Kaplan-Meier curves revealed decreased combined inpatient and 30-day mortality among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank chi(2) = 3.93, P = 0.048). The decrease in mortality associated with A-L was maintained in the most clinically ill patients determined by Karnofsky Performance Scores

Objective: Clinical scar assessment lacks standardized methodology and consensus on the most appropriate evaluation instrument. This study empirically evaluated whether area scars could be validly assessed by naive observers with the objective to develop and validate a novel multidimensional visual analogue scale (VAS) for the assessment of area scars., Methods: Standardized digital photographs of radial forearm free flap (RFFF) donor sites were obtained. Naive observers evaluated the images in three sequential psychophysical experiments, which led to the development of the new scar scale. These experiments involved initial evaluation of four dimensions (pigmentation, vascularity, observer comfort, acceptability) using a paired comparison (PC) paradigm and correlation with ratings of overall severity using a VAS, and initial VAS test phase followed by formal debriefing, and, subsequently, evaluation of a VAS for the four dimensions in addition to contour. Validation involved determination of intra- and interrater reliability and correlational analysis., Results: Across all three experiments, 56 observers evaluated 101 images, generating 12 720 observations for analysis. PC data demonstrated that observers could assess scars with high reliability and internal consistency for all dimensions (> 95%). Overall (VAS) severity correlated highly with all dimensions, including contour. The new VAS yielded high levels of correlation (r = .72-.98, p < .01)., Conclusion: Comprehensive VAS analysis demonstrates high reliability in mirroring PC results for multiple dimensions of area scars. These data support our novel multidimensional VAS method as a valid, reliable, simple, and time-efficient instrument for clinical and research use. We introduce the Western Scar Index as a new measurement tool with many potential applications.

Objective: This study assessed the utility of focused scar injury with an ink-free tattooing technique combined with UV light exposure for the treatment of hypopigmented cervicofacial scars., Study Design: Pilot prospective, randomized, control trial., Subjects: Individuals with long-standing hypopigmented cervicofacial scars., Methods: Twenty individuals randomly underwent UVA light exposure with or without dry tattooing. Scars were evaluated pretreatment and at seven-months post-treatment. Outcome measures included observer and patient subjective assessment of the scar, and objective evaluation of the erythema and melanin content of the scar and the surrounding skin., Results: The tattoo group demonstrated statistically significant improvement in the subjective evaluation of their scars. Scar melanin content reached equivalence with the surrounding skin. Observer and patient subjective global ratings support the use of dry tattooing., Conclusions: Dry-tattooing followed by UV light exposure may provide a safe and effective means for the treatment of hypopigmented scars.

Background: Many novel therapeutics have failed to reduce all-cause mortality associated with severe sepsis. Eukaryotic translation initiation factor 5A (eIF5A) is a regulator of apoptosis as well as inflammatory cell activation, making it a potential target for sepsis therapy., Methods: In a murine model of severe sepsis, mice were intraperitoneally challenged with lipopolysaccharide (LPS). Mice were treated both before and after LPS challenge with liposome complexes containing either an eIF5A-specific or control small interference RNA (siRNA), and both survival and serum concentrations of inflammatory cytokines were monitored. The ability of eIF5A siRNA to reduce inflammatory cytokines was also tested in a model of acute lung injury established by intranasal administration of LPS to mice., Results: There was a statistically significant increase in the rate of survival for mice intraperitoneally challenged with LPS that received eIF5A siRNA, compared with that noted for mice that received control siRNA (71% vs. 5%; P< .001), as well as a reduction in cytokine expression in serum. Concentrations of proinflammatory cytokines were also reduced in the lung homogenates and serum of mice that were intranasally challenged with LPS and received eIF5A siRNA (P< or = .05)., Conclusions: eIF5A siRNA-liposome complexes reduced inflammation and contributed to increased survival in a model of severe sepsis, decreased inflammation in a model of acute lung injury, and should be considered for clinical use.

Objective: This study assessed rhinometric improvement in nasal airflow, perceived comfort, and the utility of nasal dilation devices for individuals with nasal obstruction treated with an external nasal dilator (END) or a novel internal nasal dilation stent (INDS)., Study Design: Prospective, randomized, crossover trial., Subjects: Individuals with symptoms of nasal obstruction., Methods: Twenty-three participants underwent rhinometry and a trial with a novel INDS and a validated END. Devices were used in a randomized, crossover fashion. Nasal airflow, maximum use, continuous use, comfort, and challenge with these devices were assessed., Results: The END and INDS showed greater nasal airflow from baseline, with the INDS being significantly better than the END. The INDS was used significantly more than the END, and demonstrated significantly greater comfort and less associated challenge., Conclusions: The novel INDS showed 3.4 times improved nasal airflow from baseline, was used maximally and continuously longer than a validated END, and was judged to be significantly more tolerable.

Background: Prediction of mortality may improve management and outcomes of patients with sepsis in resource-limited settings. Therefore, we evaluated the ability of a hand-held portable whole-blood lactate (PWBL) analyzer to predict mortality of patients who are admitted to the hospital with severe sepsis., Methods: A prospective observational study enrolled 253 patients at a national referral hospital in Uganda. Inclusion criteria required (1) >or=2 systemic inflammatory response syndrome criteria or thermodysregulation, (2) hypotension, and (3) suspected infection. A subset of 72 patients had PWBL and standard laboratory serum lactate measured. The primary measured outcome was in-hospital mortality., Results: Fifty-nine (81.9%) of 72 evaluated patients were infected with human immunodeficiency virus type 1. The in-hospital mortality rate was 25.7% (18 of 70), and the in- and outpatient mortality at 30 days was 41.6% (30 of 72). PWBL was positively associated with in-hospital but not outpatient mortality (P=.001). The receiver operating characteristic area under the curve for PWBL was 0.81 (P=.081). The optimal PWBL concentration for predicting in-hospital mortality (sensitivity, 88.3%; specificity, 71.2%) was >or=4.0 mmol/L. Patients with a PWBL concentration >or=4.0 mmol/L died while in the hospital substantially more often (50.0%) than did those with a PWBL concentration <4.0 mmol/L (7.5%) (odds ratio, 12.3; 95% confidence interval, 3.5-48.9; [P=.001). Standard laboratory serum lactate results were inconsistent and less predictive of mortality than were those of PWBL in a multiple logistic regression model., Conclusion: A PWBL concentration >or=4.0 mmol/L predicts with 81% accuracy a 7-fold higher mortality of patients with sepsis than does a PWBL concentration <4.0 mmol/L. PWBL testing would be useful in places where clinical decisions are limited by lack of laboratory infrastructure and poor reliability.

Endoscopic repair of orbital blow-out fractures could become a predictable and efficient treatment alternative to traditional methods. However, maxillary sinus endoscopy provides a complex and disorienting view of the orbital floor. To be a useful and consistent technique for providing access to the orbital floor, specific knowledge of maxillary endoscopic anatomy is required. The purpose of the study was to provide an anatomic description of the orbital floor via the endoscopic approach. Objectives include defining consistent landmarks for use in endoscopic repair of orbital floor fractures. Using 0- and 30-degree rigid endoscopes, 6 fresh cadavers (12 maxillary sinuses) were examined via a standard Caldwell-Luc approach. Computed tomographic scans, plastic molds, and digital images were used to compare observable averages within bony anatomy. Potential bony landmarks were correlated with soft-tissue anatomy in fresh specimens. The maxillary ostium, orbital floor, and lateral ethmoid air cells were visualized, and their structures were described. Observations were made in relation to the anatomy of the orbital floor and maxillary sinus, including fracture pattern and force transmission pathways. An "orbitomaxillary" sinus bony thickening was identified and described for the first time. This study provides the basis for further refinement of surgical technique and opens the door for future clinical trials using endoscopic repair.

Objective: To evaluate changes in dermal characteristics with subdermal fat grafting of cutaneous scars., Design: Prospective cohort., Methods: Fourteen patients with various scar types were treated with subdermal fat grafting over 30 months. Dermal elasticity, vascularity, pigmentation, patient perception and satisfaction, and observer assessment of scar characteristics were evaluated preoperatively and 1 year after treatment with validated objective and subjective measures., Results: Significant improvements were observed in dermal elasticity, patient and observer perception of scar thickness, patient perception of stiffness, and observer perception of relief and pliability (P < 0.05). A trend toward significance was seen in observer assessment of height as evaluated by the Vancouver Scar Scale (P < 0.1). No significant differences were seen in quantitatively and qualitatively measured vascularity and pigmentation (P > 0.1). No significant difference in pain, pruritus, and irregularity were reported (P > 0.1)., Conclusion: Although fat grafting represents a subdermal process, it appears to improve certain quantitative and qualitative dermal characteristics. Fat grafting does not appear to affect skin color, vascularity, or patient symptoms.

Objective: To determine if rounding of the inferior rectus muscle on coronal computed tomographic (CT) scans predicts disruption of the periorbita in orbital floor fractures and therefore predicts delayed enophthalmos., Design: Cadaveric study with CT scan analysis., Setting: Cadaveric laboratory and CT scanner at a tertiary care hospital in London, Ontario., Methods: Each orbit of each cadaveric head was randomly assigned to have either intact or disrupted periorbita. Progressively larger orbital floor fractures were made and CT scans were taken before fractures and after each fracture to assess the shape of the inferior rectus muscle. Measurements were made of the length of the long and short axis of the inferior rectus muscle using CT analysis software. The short to long axis ratio was then compared., Main Outcome Measures: Change in the short to long axis ratio of the inferior rectus muscle and correlation of the ratio with intact and disrupted periorbita., Results: Orbital floor fractures measuring 1 x 1 cm show an increase in the short to long axis ratio (rounding) of the inferior rectus muscle only if the periorbita is disrupted. Orbital floor fractures measuring 2 x 2 cm show rounding of the inferior rectus muscle regardless of whether the periorbita is intact or disrupted; however, the degree of rounding is greater if the periorbita is disrupted., Conclusions: For small orbital floor fractures, rounding of the inferior rectus muscle predicts periorbital disruption. This may therefore represent an indication for early surgical repair to prevent delayed enophthalmos.

Objective: Protoporphyrin IX (PpIX) is an endogenous photosensitizer commonly used in photodynamic therapy. This study sought to assess if PpIX fluorescence can be applied clinically to improve the delineation and excision of nonmelanotic cutaneous malignancies., Design: Prospective, randomized control trial., Setting: A tertiary care skin cancer clinic., Methods: Fifty-one individuals with 65 cutaneous nonmelanotic cervicofacial malignancies were randomized into two groups. The control group was offered surgical excision with surgeon-delineated excision margins. The study group had their excision margins delineated while under fluorescence., Main Outcome Measures: The delineated lesion borders, proposed excision margins, and projected lesion-free areas were compared among the two groups. Pathologic resection margins and completeness of excision were also assessed., Results: Excisions performed using fluorescence delineation were 20% narrower (p < .01) and 17% shorter (p < .04), with 35% less lesion-free skin excised (p < .005). All lesions excised using photodelineation had clear pathologic resection margins. A significant number of lesions excised via the traditional approach required reexcision owing to pathologically positive peripheral margins (p < .001). Follow-up at 2 years revealed no lesion recurrence among the study group and one recurrence within the control group., Conclusion and Significance: The results demonstrate a reliable and novel application for photodynamic photodelination and support its application in the excision of nonmelanotic cutaneous malignancies.

In spite of established indications for early operative repair of orbital floor fractures 7-10% of patients treated nonoperatively develop enophthalmos. Clearly further indications for repair are required to prevent these post-injury complications. Rounding of the inferior rectus muscle on coronal computerized tomography (CT) scan results from a loss of soft tissue and bony support and may therefore be predictive of late enophthalmos.A four-year institutional review was conducted to identify patients with orbital floor fractures that had been treated nonoperatively. Patients were recruited for late clinical follow-up (mean 30 months) where clinically significant enophthalmos and diplopia were measured. Clinical results were correlated with measurements of the height-to-width ratio of the inferior rectus muscle on CT scans by a blinded examiner. Eighteen of 78 patients were available for late follow-up. Sixteen patients had no enophthalmos whereas 2 patients had enophthalmos. The inferior rectus height-to-width ratios measured in the unaffected orbits were statistically similar between the two groups. There was a significantly increased height-to-width ratio exceeding 1.00 in the affected orbit when the enophthalmos group was compared to the no enophthalmos group.A height-to-width ratio of the inferior rectus muscle on coronal CT scan of greater than or equal to 1.00 is predictive of late enophthalmos.

Objective: To determine the efficiency (and accuracy) of endoscopic repair versus transconjunctival repair for orbital floor fractures in a cadaveric model., Methods: In nine fresh cadavers, a standardized technique created orbital floor fractures. One orbit was repaired using an endoscopic transantral approach, whereas the other was repaired using a standard transconjunctival approach. Commercially available implants were used for floor reconstruction. A validated computed tomographic volumetric analysis of the orbits was performed at three time points: prefracture, postfracture, and postrepair. Student's t-test analyzed the percentage of volume change in the prefracture and postrepair stages for each approach., Results: The percentage of change between the prefracture and postrepair states was not statistically significant for transconjunctival (p = .834) or endoscopic (p = .366) repair. The average differences between transconjunctival repair and endoscopic repair were not statistically significant (p = .732)., Conclusions: This study objectively confirms the efficiency of the endoscopic repair of orbital floor fractures when compared with traditional techniques in the cadaveric model.

Objective: It is proposed to test the practicality of septopalatal protraction in the unilateral cleft palate infant for purposes of straightening the nasal septum and thus relieving nasal airflow obstruction and its detrimental sequelae., Methods: Alternate infants affected with complete unilateral palatal clefts had septopalatal protraction for a period of 6 to 8 weeks (protraction group; n = 4). Septal deviation was measured by a standardized technique that used computed tomography scans. The remaining infants had no protraction and served as controls (nonprotraction group; n = 5). Septal deviation was measured in the nonprotraction group from palatoseptal dental molds., Results: A total of 9 patients were studied. All patients in the nonprotraction group had worsening of nasal septal deviation over a period of 8 weeks compared with the protraction group, which had complete nasal septal straightening. Differences in septal angle deviation between the protraction group and nonprotraction group at the end of the study were statistically significant (P < or = 0.01) as measured by the paired Student t test., Conclusions: Septopalatal protraction in the newborn appears to provide a means for correcting nasal septal deviation in complete unilateral cleft palate infants. Septopalatal protraction in the newborn is relatively easy and safe.

The present work has as its purpose a description of the information exchanged during doctor-patient encounters immediately following diagnosis of pulmonary tuberculosis. To accomplish this nine such encounters were audiotape at two public health clinics in Guadalajara, Mexico. Communication of information and affect was evaluated by adapting the Roter interactional process analysis. Results show that the physician instructed the patient to behave in ways to prevent disease transmission while assuring patient recovery. Virtually lacking from these recordings is evidence of physician concern with the struggle patients experience to incorporate this regimen of directly observed therapy in to their daily lives. Because these sessions are managed by clinicians to encourage a unidirectional flow of information from physician to patient, the former fail to attain either patient cultural understanding of his/her disease process or comprehensive understanding of how he is affected she by the illness.

Results of studies of the popular illness susto and the biomedical entity pulmonary tuberculosis are offered to illustrate how comparisons of sick and well people can elucidate societal processes in cultural anthropology.

Streptococcus pneumoniae is a common cause of infection in the pediatric population, as well as an important cause of septic arthritis. The increased prevalence of drug-resistant S pneumoniae in North America has renewed interest in the use of pneumococcal vaccines. We describe the case of a child with isolated acute septic arthritis caused by infection with penicillin-resistant S pneumoniae.

Chromobacterium violaceum sepsis, a rarely reported phenomenon, has a high mortality rate. We report a unique case of C. violaceum sepsis in an infant. A 4-month-old girl presented to our institution with fever, pustular skin lesions, and distended abdomen, as well as diminished activity and mental status. Radiological investigation revealed brain, lung, and hepatic abscesses. The infant was successfully treated with trimethoprim-sulfamethoxazole and ciprofloxacin.

Magnetic resonance imaging with tissue tagging is a noninvasive technique for measuring three-dimensional motion and deformation in the human heart. Tags are regions of tissue whose longitudinal magnetization has been altered before imaging so that they appear dark in subsequent magnetic resonance images. They then move with the underlying tissue and serve as easily identifiable landmarks within the heart for the detailed detection of motion. Many different motion and strain parameters can be determined from tagged magnetic resonance imaging. Strain components that are based on a high density of tag data, such as circumferential and longitudinal shortening, or parameters that are combinations of multiple strain components, have highest measurement precision and tightest normal ranges. The pattern of three-dimensional motion and strain in the heart is important clinically, because it reflects the basic mechanical function of the myocardium at both local and global levels. Localized abnormalities can be detected and quantified if the pattern of deformation in a given heart is compared to the normal range for that region, because normal motion and strain in the left ventricle is spatially heterogeneous. Contraction strains typically are greatest in the anterior and lateral walls and increase toward the apex. The direction of greatest contraction lies along a counter clockwise helix from base to apex (viewed from the base) and approximates the epicardial muscle fiber direction. This fiber geometry also results in long-axis torsion during systole. Ejection is accomplished primarily by radially inward motion of the endocardium and by descent of the base toward the apex during systole.

The ability of a physiological dose of estrogen (estradiol benzoate, estrogen: 10 microgram 48 and 24 h prior) to modulate autoreceptor-mediated changes in dopamine transport properties was investigated in a synaptosomal preparation prepared from the nucleus accumbens of ovariectomized rats. Quinpirole (1-100 microM)-mediated potentiation of [3H]dopamine uptake was attenuated in synaptosomes from estrogen-primed animals. Haloperidol (10 microM) inhibited basal uptake and effectively prevented quinpirole potentiation of uptake in both ovariectomized and estrogen-primed samples. The ability of selective protein phosphatase inhibitors to modulate autoreceptor-mediated potentiation of dopamine uptake was also examined. Pretreatment with protein phosphatase 2B (deltamethrin, cypermethrin) or protein phosphatase 1 (tautomycin) inhibitors attenuated basal and quinpirole-potentiated dopamine uptake in ovariectomized but not estrogen-primed tissue. These data suggest that autoreceptor-mediated activation of dopamine transport can be regulated by physiological doses of estrogen and implicate a role for protein phosphorylation in autoreceptor-mediated potentiation of dopamine uptake.

Two perceptual structures (based on colors) and one semantic structure (based on names) of eight basic chromatic colors were obtained from three judged similarity tasks for 41 Mandarin Chinese-speaking females in Taiwan and 35 English-speaking females in the United States. Major findings include the following: (i) there are robust and reliable individual differences among individuals, (ii) the structures for Chinese and English speakers are similar, and (iii) the semantic structure of color names is similar to the perceptual structures of colors. The results place strong constraints on theories relating to individual differences, linguistic relativity, and the relation of perceptual and semantic structures for colors.

Purpose: To present a database of systolic three-dimensional (3D) strain evolution throughout the normal left ventricle (LV) in humans., Materials and Methods: In 31 healthy volunteers, magnetic resonance (MR) tissue tagging and breath-hold MR imaging were used to generate and then detect the motion of transient fiducial markers (ie, tags) in the heart every 32 msec. Strain and motion were calculated from a 3D displacement field that was fit to the tag data. Special indexes of contraction and thickening that were based on multiple strain components also were evaluated., Results: The temporal evolution of local strains was linear during the first half of systole. The peak shortening and thickening strain components were typically greatest in the anterolateral wall, increased toward the apex, and increased toward the endocardium. Shears and displacements were more spatially variable. The two specialized indexes of contraction and thickening had higher measurement precision and tighter normal ranges than did the traditional strain components., Conclusion: In this study, the authors noninvasively characterized the normal systolic ranges of 3D displacement and strain evolution throughout the human LV. Comparison against this multidimensional database may permit sensitive detection of systolic LV dysfunction.

This paper describes a variety of statistical methods for obtaining precise quantitative estimates of the similarities and differences in the structures of semantic domains in different languages. The methods include comparing mean correlations within and between groups, principal components analysis of interspeaker correlations, and analysis of variance of speaker by question data. Methods for graphical displays of the results are also presented. The methods give convergent results that are mutually supportive and equivalent under suitable interpretation. The methods are illustrated on the semantic domain of emotion terms in a comparison of the semantic structures of native English and native Japanese speaking subjects. We suggest that, in comparative studies concerning the extent to which semantic structures are universally shared or culture-specific, both similarities and differences should be measured and compared rather than placing total emphasis on one or the other polar position.

Background: To limit ischemic myocardial injury, it is important to differentiate viable from infarcted myocardium. Three dimensional (3D) tagged MRI has the ability to quantify myocardial 3D deformation and strain (noninvasively and precisely), and can achieve a true comparison of contraction not only from region to region, but also at different levels of function. In this study, we investigated whether regional strain mapping obtained by 3D-tagged MRI can differentiate between viable but stunned myocardium and nonviable myocardium., Methods and Results: We examined 7 dogs 2 days after a 90-minute closed-chest left anterior descending coronary artery occlusion followed by 48 hours of reperfusion. 3D-tagged MR images spanning the entire left ventricle were acquired both at rest and during dobutamine infusion (5 microg. kg-1. min-1 IV). Regional blood flow was measured with radioactive microspheres and used to define risk regions. Infarcted regions were defined as 2,3,5 triphenyltetrazolium chloride negative regions. Strains in infarcted regions were greatly impaired compared with remote regions (P<0.001) and remained unchanged during dobutamine stress. Risk regions showed a dysfunction at rest, with improved function during dobutamine infusion. Receiver operating characteristics analysis showed that radial strain was more accurate for identifying viable regions., Conclusions: When coupled with a stress test, 3D strain mapping by the use of tagged MRI is a sensitive and noninvasive method for characterizing ischemic injury. Regional strain can be used to differentiate between viable but stunned and nonviable myocardium within the postischemic injured myocardium.

The purpose of this study was to investigate the relationship between three-dimensional (3D) deformation patterns in the canine left ventricle and localized graded reductions in perfusion. Magnetic resonance (MR) tissue tagging in a clinical scanner was used to determine systolic 3D deformation throughout the left ventricle with 32-msec time resolution. Six dogs were studied at normal and reduced left anterior descending coronary artery flow levels, for a total of 14 studies. Deformation was calculated by fitting a 3D displacement field to tag displacement data from three orthogonal sets of tags and taking spatial derivatives. A novel index of 3D radial mechanical function, calculated from the 3D strain tensor components and the tissue incompressibility constraint, had a higher correlation (R = 0.94) with perfusion (colored microspheres) than any of the 3D Lagrangian finite strain tensor components or wall thickening. As a function of the fraction of baseline perfusion, it was well fit by a linear relationship for subnormal perfusion with a slope of 0.46 +/- 0.05 and an intercept of -0.156 +/- 0.026. Longitudinal strain was lost first with decreasing perfusion (48%), followed by circumferential (40%) and finally radial function (35%). The strain method detected perfusion drops as small as 20%, and early paradoxical strain transients lasting 100 msec were seen only with ischemia. 3D strain changes can be noninvasively measured throughout the left ventricle with MR tissue tagging. MR imaging-derived strain indices, unique to 3D analysis, correlate most sensitively with regional perfusion in the canine left ventricle.

Research is presented on the semantic structure of 15 emotion terms as measured by judged-similarity tasks for monolingual English-speaking and monolingual and bilingual Japanese subjects. A major question is the relative explanatory power of a single shared model for English and Japanese versus culture-specific models for each language. The data support a shared model for the semantic structure of emotion terms even though some robust and significant differences are found between English and Japanese structures. The Japanese bilingual subjects use a model more like English when performing tasks in English than when performing the same task in Japanese.

Culture consists of shared cognitive representations in the minds of individuals. This paper investigates the extent to which English speakers share the "same" semantic structure of English kinship terms. The semantic structure is defined as the arrangement of the terms relative to each other as represented in a metric space in which items judged more similar are placed closer to each other than items judged as less similar. The cognitive representation of the semantic structure, residing in the mind of an individual, is measured by judged similarity tasks involving comparisons among terms. Using six independent measurements, from each of 122 individuals, correspondence analysis represents the data in a common multidimensional spatial representation. Judged by a variety of statistical procedures, the individuals in our sample share virtually identical cognitive representations of the semantic structure of kinship terms. This model of culture accounts for 70-90% of the total variability in these data. We argue that our findings on kinship should generalize to all semantic domains--e.g., animals, emotions, etc. The investigation of semantic domains is important because they may reside in localized functional units in the brain, because they relate to a variety of cognitive processes, and because they have the potential to provide methods for diagnosing individual breakdowns in the structure of cognitive representations typical of such ailments as Alzheimer disease.

Purpose: To reconstruct three-dimensional (3D) myocardial deformations from orthogonal sets of parallel-tagged magnetic resonance (MR) images., Materials and Methods: Displacement information in the direction normal to the undeformed tag planes was obtained at points along tag lines. Three independent sets of one-dimensional displacement data were used to fit an analytical series expression to describe 3D displacement as a function of deformed position. The technique was demonstrated with computer-generated models of the deformed left ventricle with data from healthy human volunteers., Results: Model deformations were reconstructed with a 3D tracking error of less than 0.3 mm. Error between estimated and observed one-dimensional displacements along the tags in 10 human subjects was 0.00 mm +/- 0.36 (mean +/- standard deviation). Robustness to noise in the tag displacement data was demonstrated by using a Monte Carlo simulation., Conclusion: The combination of rapidly acquired parallel-tagged MR images and field-fitting analysis is a valuable tool in cardiac mechanics research and in the clinical assessment of cardiac mechanical function.

Normal male sex differentiation requires that Sertoli cells in the embryonic testes produce müllerian inhibiting substance (MIS), a TGF beta-like hormone that causes müllerian duct regression. In primary Sertoli cells, the orphan nuclear receptor, steroidogenic factor 1 (SF-1), regulates the MIS gene by binding to a conserved upstream regulatory element. In heterologous (HeLa) cells, MIS gene activation by SF-1 requires removal of the SF-1 ligand-binding domain, implicating a Sertoli cell-specific ligand or cofactor. Finally, the sexually dimorphic expression of SF-1 during development coincides with MIS expression and müllerian duct regression. We propose that SF-1 regulates MIS in vivo and participates directly in the process of mammalian sex determination.

The imaging modalities used to study the mechanism of cardiomyoplasty, such as echocardiography and radionuclide scintigraphy, are seriously limited by their two-dimensional format. Radiofrequency-pulse-tagged magnetic resonance imaging was used to generate three-dimensional reconstructions of the left ventricle throughout the cardiac cycle after cardiomyoplasty. In 2 dogs that had undergone conditioned, right anterior cardiomyoplasty, wrap stimulation with alternating heartbeats was found to produce marked translation of the left ventricle in the short-axis plane, rotation around the long axis, and displacement along the long axis with net long-axis compression; there was no augmentation of radial squeeze. The findings from this study suggest that any systolic augmentation produced by the right anterior wrap is due primarily to long-axis compression. Our study demonstrates a new, more accurate technique of assessing the mechanical effects of cardiomyoplasty in three dimensions, thus permitting a more rational optimization of wrap configurations, and emphasizes the perils of using standard two-dimensional imaging modalities in this setting of exaggerated three-dimensional motion.

Purpose: To validate cine magnetic resonance (MR) image tagging measurements of a deforming object by means of a precise photographic method., Materials and Methods: A piece of silicone rubber that acted as a phantom was stretched in a cyclical fashion inside a plastic clamp driven by a respirator pump. Deformation as a function of time was measured with a rapid gradient-echo cine tagging sequence and with sequential stroboscopic photographs. Deformations from 1.0 to 1.2 (0% to 20% stretch) in the readout direction were measured over a 7-cm region of the phantom, which had a maximum standard error of +/- 0.001 with photography and a maximum standard error of +/- 0.003 with MR imaging., Results: The deformation versus time values measured with MR imaging had a standard error of 0.002 about a straight line fit to the photographic deformation versus time data. These results demonstrate that the MR imaging deformation estimates were accurate and precise., Conclusion: The validated tagging method can now be used to evaluate MR imaging motion estimation techniques.

Studies of adrenal steroidogenesis have been facilitated by the availability of immortalized mouse adrenocortical Y-1 cells. We sought to make new, alternative mouse steroidogenic cell lines by genetically targeted tumorigenesis. Transgenic mice were constructed expressing both the SV40 T-antigen and a bacterial neomycin-resistance gene under the control of the promoter for the human P450 cholesterol side-chain cleavage (P450scc) gene, which encodes the first and rate-limiting enzyme in steroidogenesis. Two female transgenic mice expressed T-antigen in various nonsteroidogenic tissues but generated tumors only in the adrenals, suggesting adrenal tumor formation was an early event. Ovarian tissues, which, unlike the adrenal, do not make steroids in fetal or early postnatal life, did not develop tumors. Cell lines derived from the adrenal tumors were resistant to the neomycin analog G418. Clonal sublines are stable, growing easily in monolayers with a doubling time of 24-60 h. The cell lines secrete progesterone and 11-deoxycorticosterone, indicating these cells express the P450scc system, 3 beta-hydroxysteroid dehydrogenase, and 21-hydroxylase activity. However the 21-hydroxylase activity was not mediated by P450c21, as the cells lacked P450c21 mRNA. The cells did not secrete any 11-hydroxylated steroids, although they contained P450c11 beta mRNA. Both the secretion of progesterone and the abundance of P450scc mRNA increase in response to 8-bromo-cAMP, but not to ACTH or angiotensin II. In addition to expression of steroidogenic enzyme mRNAs, one cell line also expresses mouse renin-1 mRNA, making these cells useful for studies of the role of adrenal renin in regulating adrenal steroidogenesis. These findings represent an approach in transgenic mice to develop highly differentiated adrenal cell lines.