Impact of variant histology on upstaging and survival in patients with nonmuscle invasive bladder cancer undergoing radical cystectomy.

INTRODUCTION: Variant histology (VH) of urothelial carcinoma is uncommon and frequently presents at the muscle-invasive stage. VH is considering a significant risk factor for progression among patients with nonmuscle invasive bladder cancer (NMIBC). While there is some debate, expert opinion is generally that upfront radical cystectomy (RC) should be consider for these patients. Limited data exists to support this position. In this study, we sought to examine the rate of upstaging and overall survival for patients with VH NMIBC against patients with pure urothelial NMIBC who underwent RC, to help clarify the optimal treatment strategy for these patients. METHODS: The institutional REDCap database was utilized to identify all patients with T1 and Ta bladder cancer that underwent RC over the study period (2004-2022). Matched-pair analysis was performed between patients with VH and pure urothelial NMIBC; 42 pairs were matched on prior intravesical therapy, presence of muscularis propria on transurethral resection of bladder tumor (TURBT), any carcinoma in situ presence on prior TURBTs, and final tumor staging on TURBT. The primary outcomes of interest were pathologic tumor upstaging rate at RC and overall survival. Secondary outcomes of interest included association of demographic or pretreatment variables with upstaging, and upstaging rates for specific variant histologies. RESULTS: Patients with VH NMIBC undergoing RC were upstaged at a significantly higher rate than a matched cohort of patients with pure urothelial NMIBC (73.8% vs. 52.4%, P = 0.0244) and among those upstaged, had significantly higher rates of pT3 to pT4 (54.7% vs. 23.8%, P = 0.0088). Rate of node positivity at RC for VH NMIBC was also higher compared to pure urothelial NMIBC (40.5% vs. 21.4%, P = 0.0389). Among histologic variants, patients with plasmacytoid and sarcomatoid subtypes demonstrated the highest rates of upstaging; differences were not statistically significant. The overall median survival was 28.4 months for patients with VH after RC compared to 155.1 months for patients with pure urothelial NMIBC (P = 0.009). CONCLUSION: Patients with VH NMIBC undergoing RC are at significantly higher risk of upstaging at RC when compared to patients with pure urothelial NMIBC and have worse overall survival. While this study supports the concept of an aggressive treatment approach for patients with VH NMIBC, improvements in understanding of the disease are necessary to improve outcomes.

Is there a relationship between malocclusion and bullying? A systematic review.

BACKGROUND: Malocclusion is a highly prevalent public health problem, and several studies have shown its negative correlation with quality of life, self-esteem, and social perceptions. However, its association with bullying is still controversial. OBJECTIVES: To evaluate the relationship between malocclusion and bullying in children and adolescents. SEARCH METHODS: The databases used for the electronic researches were PubMed, Scopus, Lilacs/BBO, Web of Science, and Cochrane Library. Grey literature was reviewed through Open Grey literature with no language or date restrictions. Selection criteria, based on the PECO strategy, were considered eligible observational studies that included schoolchildren or adolescents (P) with malocclusion (E), compared to those with normal occlusion (C), in which the relationship between malocclusion and bullying was determined (O). DATA COLLECTION AND ANALYSIS: Risk of bias evaluation was made for the qualitative synthesis by the Fowkes and Fulton criteria. Data regarding the age of participants and types of malocclusion and of bullying were extracted among other reported data. The quality of the evidence analyzed was evaluated through the GRADE approach. RESULTS: From 2744 articles identified in databases, nine met the eligibility criteria and were included in present systematic review, of which two studies were judged with methodological soundness. The quality of the evidence was classified as very low due to very serious problems for "risk of bias" and "other considerations" and serious problems of "indirectness". The age of participants ranged from 9 to 34 years considering a cohort study, with a bullying recalling perspective. Malocclusion was both evaluated by researchers and self-reported by participants addressing dentofacial characteristics mostly related to the incisors relationship. All studies evaluated the verbal type of bullying, while 3 also considered physical type. Both types were reported as related to malocclusion, although the results showed that extreme maxillary overjet (> 4 mm, > 6 mm, > 9 mm), extreme deep overbite, and having space between anterior teeth or missing teeth were the types of malocclusion with the strongest relations to bullying. CONCLUSIONS: With very low certainty of evidence, the results of this systematic review suggest that conspicuous extreme malocclusion may be related to the occurrence of bullying among children and adolescents.

Variation in collagenase Clostridium histolyticum practice patterns: a Survey of ISSM Members.

Collagenase clostridium histolyticum (CCH, Xiaflex, Xiapex) is the only FDA-approved medication for treatment of Peyronie's disease. It is unclear how practitioners actually use CCH in their own practices. The objectives of the study were: (1) to identify variability in practice patterns for CCH among practitioners, (2) to assess adherence to the package insert instructions, and (3) to evaluate whether provider satisfaction was associated with adherence to instructions. A 30-question online survey was distributed to 1270 members of the International Society for Sexual Medicine (ISSM) from the EU, USA, Canada and Australia. Of the 30 questions, 10 survey questions had only one response consistent with the CCH package insert recommendations. An "adherence" score was calculated for each survey participant depending on how many of these questions were answered correctly. The average adherence scores of various groups were compared using a student's t-test. A chi-squared test was used to determine association between categorical variables. Of 202 total responses, 132 practitioners reported using CCH out of 1270 ISSM members from countries where CCH is available (10.4% response rate). Practitioners from outside the USA were more likely to be satisfied with CCH (p = 0.006), and more experienced users (>20 uses) were more likely to be satisfied than less experienced users (<10 uses) (p = 0.046). Satisfied users of CCH did not have significantly different adherence scores than non-satisfied users. Even though 67% of practitioners believed they followed the package insert guidelines, only 11% adhered to all the recommendations evaluated by the survey. Treatment adherence to package insert guidelines does not appear to be associated with provider satisfaction. We believe there is utility in seeing a snapshot of these practice patterns so practitioners may feel more comfortable adapting their own practice in light of newer data supporting alternative administration methods.

Increased brain and behavioural susceptibility to portion size in children with loss of control eating.

BACKGROUND: Portion size influences intake (i.e. the portion size effect [PSE]), yet determinants of susceptibility to the PSE are unclear. OBJECTIVE: We tested whether children who reported an episode of loss of control (LOC) eating over the last 3 months would be more susceptible to the PSE and would show differential brain responses to food cues compared with children with no-LOC. METHODS: Across five sessions, children (n = 47; 7-10 years) consumed four test meals at 100%, 133%, 167% and 200% conditions for portion size and completed a functional magnetic resonance imaging scan while viewing pictures of foods varied by portion size and energy density (ED). Incidence of LOC over the past 3 months was self-reported. Random coefficient models were tested for differences in the shape of the PSE curve by LOC status. A whole-brain analysis was conducted to determine response to food cues during the functional magnetic resonance imaging. RESULTS: Reported LOC (n = 13) compared with no-LOC (n = 34) was associated with increased susceptibility to the PSE, as evidenced by a positive association with the linear slope (P < 0.005), and negative association with the quadratic slope (P < 0.05) of the intake curve. Children who reported LOC compared with no-LOC showed increased activation in the left cerebellum to small relative to large portions (P < 0.01) and right cerebellum to High-ED relative to Low-ED food cues (P < 0.01). CONCLUSION: Children who reported LOC were more susceptible to the PSE and showed alterations in food-cue processing in the cerebellum, a hindbrain region implicated in satiety signalling.

Commentary on "Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy."

BACKGROUND: Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. MATERIALS AND METHODS: Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. RESULTS: A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19-13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. CONCLUSION: The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.

Does flavoured dentifrice increase fluoride intake compared with regular toothpaste in children? A systematic review and meta-analysis.

BACKGROUND: Toothpaste manufacturers encourage through aggressive marketing strategies the overconsumption of fluoridated dentifrices. There are conflicting results regarding fluoride intake from toothpastes in children. AIM: The aim of this systematic review and meta-analysis was to determine whether dentifrice flavour increases fluoride ingestion by children. DESIGN: We included clinical trials on children that evaluated the use of flavoured dentifrice - FD vs regular dentifrice - RD to identify the fluoride intake. An electronic search was performed in PubMed, Web of Science, Scopus, The Cochrane Library, LILACS/BBO, and grey literature followed by manual search. The methodological quality of the studies was assessed using the Cochrane Collaboration common scheme for bias and ROBINS-I tool. Data were analysed in subgroups such as low (G1) and ordinary (G2) fluoride concentrations of dentifrices. We carried out heterogeneity and sensitive analyses. RESULTS: For G1, the fluoride intake from RD was significantly higher than from FD [standardised mean difference = -2.57 (-3.26, -1.89), P < 0.00001]. For G2, the fluoride ingestion from RD was significantly higher than from FD [mean difference = -0.00 (-0.00, -0.00), P = 0.02]. CONCLUSIONS: There is evidence to support the null hypothesis that flavouring from dentifrice does not increase fluoride intake in young children.

Multidisciplinary clinic approach improves overall survival outcomes of patients with metastatic germ-cell tumors.

Background: To report our experience utilizing a multidisciplinary clinic (MDC) at Indiana University (IU) since the publication of the International Germ Cell Cancer Collaborative Group (IGCCCG), and to compare our overall survival (OS) to that of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program. Patients and methods: We conducted a retrospective analysis of all patients with metastatic germ-cell tumor (GCT) seen at IU from 1998 to 2014. A total of 1611 consecutive patients were identified, of whom 704 patients received an initial evaluation by our MDC (including medical oncology, pathology, urology and thoracic surgery) and started first-line chemotherapy at IU. These 704 patients were eligible for analysis. All patients in this cohort were treated with cisplatin-etoposide-based combination chemotherapy. We compared the progression-free survival (PFS) and OS of patients treated at IU with that of the published IGCCCG cohort. OS of the IU testis cancer primary cohort (n = 622) was further compared with the SEER data of 1283 patients labeled with 'distant' disease. The Kaplan-Meier method was used to estimate PFS and OS. Results: With a median follow-up of 4.4 years, patients with good, intermediate, and poor risk disease by IGCCCG criteria treated at IU had 5-year PFS of 90%, 84%, and 54% and 5-year OS of 97%, 92%, and 73%, respectively. The 5-year PFS for all patients in the IU cohort was 79% [95% confidence interval (CI) 76% to 82%]. The 5-year OS for the IU cohort was 90% (95% CI 87% to 92%). IU testis cohort had 5-year OS 94% (95% CI 91% to 96%) versus 75% (95% CI 73% to 78%) for the SEER 'distant' cohort between 2000 and 2014, P-value <0.0001. Conclusion: The MDC approach to GCT at high-volume cancer center associated with improved OS outcomes in this contemporary dataset. OS is significantly higher in the IU cohort compared with the IGCCCG and SEER 'distant' cohort.

Development of an autologous canine cancer vaccine system for resectable malignant tumors in dogs.

While conventional therapies exist for canine cancer, immunotherapies need to be further explored and applied to the canine setting. We have developed an autologous cancer vaccine (K9-ACV), which is available for all dogs with resectable disease. K9-ACV was evaluated for safety and immunogenicity for a variety of cancer types in a cohort of companion dogs under veterinary care. The autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies. The resultant single cell suspensions were then UV-irradiated resulting in immunogenic cell death of the tumor cells. Following sterility and endotoxin testing, the tumor cells were admixed with CpG ODN adjuvant and shipped to the participating veterinary clinics. The treating veterinarians then vaccinated each patient with three intradermal injections (10 million cells per dose) at 30-day intervals (one prime and two boost injections). In a cohort of 20 dogs completing the study, 17 dogs (85%) developed an augmented IgG response to autologous tumor antigens as demonstrated using western blot analysis of pre- and post-peripheral blood samples. We also report several dogs have lived beyond expected survival time based on previously published data. In summary, K9-ACV is an additional option to be considered for the treatment of dogs with resectable cancer.

Does trauma in the primary dentition cause sequelae in permanent successors? A systematic review.

This systematic review sought scientific evidence (in the literature) that trauma in the primary incisors cause sequelae in permanent successors. Also this work verified whether there was a relation between the presence and type of sequelae in permanent teeth with the child's age at the time of injury and type of trauma. Electronic databases, including the PubMed, Scopus, The Cochrane Library, LILACS, and Web of Science were used to search for original articles up to June 2013. Prospective and retrospective studies that assessed the association of trauma in deciduous incisors and developmental disturbances in permanent successors were selected. Two authors independently reviewed and extracted the data from the included studies. A methodological quality assessment evaluation of the selected studies was performed. The search retrieved 258 citations. Initially, 19 studies fulfilled the selection criteria; however, one (1) was excluded, leaving 18 for the final selection. Despite some limitations in the study designs were observed, especially the lack of a control group in most studies, the evidence found suggests that individuals with trauma in their primary incisors have more developmental disorders in the permanent successors than individuals without a previous trauma. Furthermore, the younger the child is at the time of injury, the more frequent and more severe are the sequelae to the permanent successor incisors. More severe traumas such as intrusion and avulsion are associated to more serious developmental disorders. These results should be analyzed carefully because very few studies evaluated had a control group.

Differentiation of prostate cancer from normal tissue in radical prostatectomy specimens by desorption electrospray ionization and touch spray ionization mass spectrometry.

Radical prostatectomy is a common treatment option for prostate cancer before it has spread beyond the prostate. Examination for surgical margins is performed post-operatively with positive margins reported to occur in 6.5-32% of cases. Rapid identification of cancerous tissue during surgery could improve surgical resection. Desorption electrospray ionization (DESI) is an ambient ionization method which produces mass spectra dominated by lipid signals directly from prostate tissue. With the use of multivariate statistics, these mass spectra can be used to differentiate cancerous and normal tissue. The method was applied to 100 samples from 12 human patients to create a training set of MS data. The quality of the discrimination achieved was evaluated using principal component analysis - linear discriminant analysis (PCA-LDA) and confirmed by histopathology. Cross validation (PCA-LDA) showed >95% accuracy. An even faster and more convenient method, touch spray (TS) mass spectrometry, not previously tested to differentiate diseased tissue, was also evaluated by building a similar MS data base characteristic of tumor and normal tissue. An independent set of 70 non-targeted biopsies from six patients was then used to record lipid profile data resulting in 110 data points for an evaluation dataset for TS-MS. This method gave prediction success rates measured against histopathology of 93%. These results suggest that DESI and TS could be useful in differentiating tumor and normal prostate tissue at surgical margins and that these methods should be evaluated intra-operatively.

Is non-cavitated proximal lesion sealing an effective method for caries control in primary and permanent teeth? A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to perform a systematic review and meta-analysis on the effectiveness of sealing non-cavitated proximal caries lesions in primary and permanent teeth. DATA: Only controlled clinical trials and randomized controlled clinical trials that evaluated the effectiveness of sealing on non-cavitated proximal caries with a minimum follow-up of 12 months were included in the study. The primary outcome should be arrestment/progression of proximal caries evaluated by bitewing radiographs. A risk of bias evaluation based on the Cochrane Collaboration common scheme for bias was carried out for each study. The meta-analysis was performed on the studies considered low risk of bias and with pair-wise visual reading results through RevMan software. SOURCES: A comprehensive search was performed in the Systematic Electronic Databases: Pubmed, Cochrane Library, Scopus, IBI Web of Science, Lilacs, SIGLE, and on website Clinical trials.gov, through until June 2013. STUDY SELECTION: From 967 studies identified, 10 articles and 3 studies with partial results were assessed for eligibility. However three articles were excluded and our final sample included 10 studies. According to the risk of bias evaluation, six studies were considered "high" risk of bias, and four "low" risk of bias. The forest plot of the meta-analysis showed low heterogeneity (I(2)=29%) and a favourable outcome for the Infiltrant. The chance of caries progression when this technique was used was significantly lower (p=0.002) compared with Placebo. CONCLUSION: Our results suggest that the technique of sealing non-cavitated proximal caries seems to be effective in controlling proximal caries in the short and medium term. Further long-term randomized clinical trials are still necessary to increase this evidence. CLINICAL SIGNIFICANCE: Contemporary dentistry is focused in minimally invasive approaches that prevent the destruction of sound dental tissues next to carious lesions. This paper searches for evidence of the efficacy of sealing/infiltrating non-cavitated proximal caries in arresting caries progression both in permanent and primary teeth.

Degrees of sexual dimorphism in Cebus and other New World monkeys.

Sexual dimorphism in primate species expresses the effects of phylogeny, life history, behavior, and ontogeny. The causes and implications of sexual dimorphism have been studied in several different primates using a variety of morphological databases such as body weight, canine length, and coat color and ornamentation. In addition to these different patterns of dimorphism, the degree to which a species is dimorphic results from a variety of possible causes. In this study we test the general hypothesis that a species highly dimorphic for one size-based index of dimorphism will be equally dimorphic (relative to other species) for other size-based indices. Specifically, the degree and pattern of sexual dimorphism in Cebus and several other New World monkey species is measured using craniometric data as a substitute for the troublesome range of variation in body weight estimates. In general, the rank ordering of species for dimorphism ratios differs considerably across neural vs. non-neural functional domains of the cranium. The relative degree of sexual dimorphism in different functional regions of the cranium is affected by the independent action of natural selection on those regions. Regions of the cranium upon which natural selection is presumed to have acted within a species show greater degrees of dimorphism than do the same regions in closely related taxa. Within Cebus, C. apella is consistently more dimorphic than other Cebus species for facial measurements, but not for neural or body weight measurements. The pattern in C. apella indicates no single best measurement of the degree of dimorphism in a species; rather, the relative degree of dimorphism applies only to the region being measured and may be enhanced by other selective pressures on morphology.

Sexual dimorphism and interspecific cranial form in two capuchin species: Cebus albifrons and C. apella.

Ontogenetic patterns of sexual dimorphism and cranial form in two capuchin monkeys, Cebus albifrons and C. apella, are investigated by means of univariate, bivariate, and multivariate statistics. The analyses are based on 23 linear variables. Univariate analyses indicate that similar ontogenetic patterns of cranial sexual dimorphism are present; however, interspecific differences exist in timing. Ontogenetic scaling is present in both species' crania; however, it is more prevalent in C. albifrons. Several departures are present in cranial regions associated with orbital shape, the dental arcade, and the muscles of mastication. The latter two indicate that sexual differences in diet and/or foraging strategies may exist. Sexual selection is suggested as being the primary selective regime underlying the observed patterns of cranial sexual dimorphism in each species. Interspecific comparisons confirm that C. apella possesses a more dimorphic cranium than C. albifrons and that sexual dimorphism in C. apella begins earlier in development. Although interspecific ontogenetic scaling is present in some cranial variables, C. apella is not just a scaled-up version of C. albifrons. These sympatric congeners seem to be differentiated by variables related to the orbital region and the masticatory apparatus, as indicated by both departures from ontogenetic scaling and results of the discriminant function analysis. Ecological selection, rather than varying degrees of sexual selection, is likely to be responsible for this finding given that C. apella is known to consume hard-object foods. This is consistent with the predicted outcome of the competitive exclusion principle.

Nutcracker syndrome: an underdiagnosed cause for hematuria?

Since its description in 1972, the Nutcracker Syndrome or Aorto-Mesenteric Left Renal Vein Entrapment Syndrome has been mentioned in the literature as an infrequent cause of hematuria originating from the left collecting system. It describes compression of the left renal vein in the fork between the abdominal aorta and the proximal Superior Mesenteric Artery (SMA), close to its origin. This results in left renal venous hypertension leading to the development of collateral veins with intrarenal and perirenal varicosities which can cause hematuria if the thin-walled septum separating the veins from the collecting system ruptures. The main presenting symptom is hematuria, with or without left flank pain. Some patients may present with left flank pain alone and, in a few, varicocele might be the only complaint. Exercise seems to aggravate the symptoms. It still remains unclear why compression of the left renal vein occurs in only a few patients despite its very peculiar course between the aorta and the SMA. Different anatomical details have been proposed. This controversy reflected itself on the lack of a clear agreement in regard to the treatment. We did a general overview of the current literature in an effort to elucidate further its pathophysiology. We present here three cases. The first case is that of a lady who presented with intermittent hematuria, sixteen years apart. Her hematuria cleared spontaneously without surgical intervention. Given her long symptom free interval, we strongly suspect some variable constitutional factors to play a role in the symptom development. The second case represents a perfectly healthy asymptomatic young women in whom an IVP done as routine renal donor work up revealed irregularities within the left collecting system that proved to be periureteric varices secondary to a nutcracker phenomenon as proved later by a renal angiogram. The third case describes a hypertensive, otherwise healthy, middle-aged male in whom an asymptomatic Nutcracker Phenomenon disclosed itself during a renal angiographic work up for his intractable hypertension. It is likely that the incidence of this anatomical problem is rather underestimated. We would like to emphasize the importance of its early inclusion in the differential diagnosis of left-sided hematuria because of the need for special testing for its diagnosis. Early proper diagnosis would spare many unneeded investigations.

Monte Carlo spreadsheet modeling of stable isotope biosynthesis.

Metabolic physiologists often introduce stable isotopes, atoms containing additional neutrons, into molecules during biosynthesis. This tags the newly synthesized material by altering its mass. Monte Carlo analysis is implemented on a popular spreadsheet to analyze this process. An example is provided where acetoacetate is synthesized by condensation of two acetate moieties. The precursor acetate is present as a mixture of natural, and 13C enriched, acetate. Monte Carlo spreadsheet modeling captures the complexity of the multi-species isotope biosynthesis by repetitively performing multiple simultaneous Boolean calculations. The effects of increasing the number of molecules synthesized on the goodness of fit of between model and an exact analytical solution is illustrated.

Isotopomer spectral analysis of cholesterol synthesis: applications in human hepatoma cells.

Cholesterol synthesis from 13C-labeled precursors produces a discrete spectrum of mass isotopomers detectable using gas chromatography-mass spectrometry. The isotopomer spectral analysis (ISA) method matches the observed spectrum of cholesterol isotopomers with a mathematical model to obtain the best fit of model spectrum to data spectrum. The model was based on multinomial probability expressions that simulate cholesterol synthesis as a condensation of mevalonate fragments. As many as four unknown parameters, representing fluxes between compartments, were included in the model. Models were developed to assess cholesterol synthesis from 13C-enriched precursors including mevalonate, acetate, acetoacetate or octanoate. Models were tested in the human hepatoma cell line, Hep G2, which readily incorporated the 13C substrates into cholesterol. The ISA approach was used to estimate the fractional amount of the cholesterol precursors derived from the 13C substrate and the fraction of total cellular cholesterol synthesized in the presence of the 13C substrate. The study demonstrated the feasibility of the ISA approach for a condensation biosynthesis that is not a simple polymerization and for models with more than two unknown parameters.

Verapamil enhances the survival of primary ischemic venous obstructed rodent skin flaps.

The effect of verapamil, a calcium channel blocker, on the survival of skin flaps subjected to primary venous obstruction was studied. Skin flaps 9 x 4 cm, which are axial patterns with random extension, were elevated in Sprague-Dawley rats. A microvascular clamp was placed on the vein alone for 8 hours. Group 1 received verapamil (0.3 mg/kg) before flap elevation and before clamp release; group 2 received saline on the same schedule. Group 3 received verapamil (0.3 mg/kg) as above, plus every 8 hours for 5 days postoperatively. Group 4 received saline on the same schedule. There was no difference in survival between groups 1 and 2. Group 3 had 100% improvement in the flap survival compared with group 4 (78% vs 37%). Verapamil, if administered for the duration of the experiment, significantly increased flap survival.

Assessing extracranial carotid stenosis: magnetic resonance angiography, duplex scanning, and digital angiography.

Recent data have demonstrated the efficacy of carotid endarterectomy in patients with severe, symptomatic carotid stenosis. In this context, our study analyzes the role of carotid testing with magnetic resonance angiography and carotid duplex scanning, as compared to arterial digital subtraction angiography.

Isotopomer spectral analysis of triglyceride fatty acid synthesis in 3T3-L1 cells.

A new analysis of stable isotope data for biosynthesis reaction, isotopomer spectral analysis (ISA), is demonstrated. ISA is theoretically applicable for polymerization biosynthesis where data are collected using selected ion-monitoring gas chromatography-mass spectrometry. ISA utilizes the discrete spectrum of isotopomer abundances and the multinomial distribution to estimate two key parameters related to the biosynthesis. These parameters are 1) the dilution of the precursor immediately before biosynthesis and 2) the dilution of the newly synthesized product in the sampled compartment. Differentiated 3T3-L1 cells incorporated 2 mM [1,2-13C]acetate into triglyceride palmitate, yielding a spectrum of mass isotopomers of palmitate. The set of equations for the first nine isotopomers were solved for the two parameters using nonlinear regression. We found that precursor dilutions for acetate and glucose were constant over time, whereas the product dilution parameter increased with time, as expected for cells accumulating triglyceride palmitate. Mathematical procedures are presented for calculating 1) the predicted isotopomer fractional abundance values and 2) the correction for atoms other than the tracer atom in the mass ion.