Gastrostomy Tube Placement in Neonates Undergoing Congenital Heart Surgery: A Novel Assessment for Improving Utilization and Timing of Placement.

BACKGROUND: Neonates undergoing congenital heart defect repair require optimized nutritional support in the perioperative period. Utilization of a gastrostomy tube is not infrequent, yet optimal timing for placement is ill-defined. The objective of this study was to identify characteristics of patients whose postoperative course included gastrostomy tube placement to facilitate supplemental tube feeding following neonatal repair of congenital heart defects. METHODS: A single-institution, retrospective chart review identified 64 consecutive neonates who underwent cardiac operations from 2012 to 2016. Perioperative variables were evaluated for significance in relation to gastrostomy tube placement. RESULTS: A total of 27 (42%) underwent gastrostomy tube placement. Diagnosis of a genetic syndrome was associated with the likelihood of placement of gastrostomy tube (P = .032), as were patients with single ventricle physiology (P = .0013) compared to those felt to be amenable to eventual biventricular repair. Aortic arch reconstruction (P = .029), as well as the need for delayed sternal closure (P = .05), was associated with increased frequency of gastrostomy tube placement. Postoperative outcomes including the number of days intubated (P = .0026) and the presence of significant dysphagia (P = .0034) were associated with gastrostomy placement. Additionally, genetic syndrome (P = .003), aortic arch reconstruction (P = .01), and postoperative intubation duration (P = .0024) correlated with increased length of stay, where increased length of stay was associated with gastrostomy tube placement (P = .0004). DISCUSSION: Patient characteristics that were associated with a high likelihood of eventual gastrostomy placement were identified in this study. Early recognition of such characteristics in future patients may allow for reduced time to gastrostomy tube placement, which in turn may improve perioperative growth and outcomes.

Impact of different surgical protocols on dimensional changes of free soft tissue autografts: A randomized controlled trial.

BACKGROUND: To determine if there is a difference in the amount of shrinkage during healing of free soft tissue autografts (FSTAs) using different surgical techniques-suturing the vestibular flap margin apically to the base of the recipient bed versus leaving the flap margin free and unsutured. METHODS: Twenty-eight patients with mucogingival defects requiring FSTAs were recruited and enrolled in the study. Patients were randomized into test and control groups (14 per group) and received ≥1 FSTAs on non-molar mandibular teeth. In the test group the mucosal flap margin was sutured apically to the periosteum at the base of the graft; whereas, the mucosal flap margin in the control group was left free. Graft dimensional measurements were taken at time of surgery, then at 1, 3, and 6 months post-surgery. RESULTS: Thirty-five grafts were performed (15 test, 20 control). All FSTAs experienced vertical shrinkage after 6 months, but there was no significant difference (P = 0.51) in the mean amount of shrinkage after 6 months between the test (23.20% ± 20.88%) and control (21.10% ± 21.88%) groups. There was significantly greater horizontal shrinkage in the test (loss of 7.59% ± 10.20%) compared with the control (small gain of 0.32% ± 4.20%) group (P = 0.01). CONCLUSIONS: The findings suggest that there is similar vertical shrinkage when performing FSTA surgery when the mucosal flap margin is left free and unsutured when compared with leaving the flap margin free.

Management of Thick and Thin Periodontal Phenotypes for Immediate Dental Implants in the Esthetic Zone: A Controlled Clinical Trial.

The goal of the study was to compare the outcome of immediate single-implant placement in esthetic sites of patients with thick or thin tissue phenotypes. Forty-one patients underwent implant surgery with guided bone regeneration including peri-implant gap and overcontour grafting. A connective tissue graft was added only for patients with a thin tissue phenotype. Twenty-six patients completed the 12-month follow-up examination (thick, n = 14; thin, n = 12). The thick-phenotype group gained 0.01 ± 1.56 mm of midfacial soft tissue height, while the thin-phenotype group lost 0.20 ± 1.14 mm (P = .21). There was no significant difference in buccal plate thickness achieved at time of uncovery, pink and white esthetic scores, radiographic bone levels, and clinical parameters between the two groups. These results suggest that when the suggested treatment protocol is followed, there are no significant differences in the outcomes of immediate implant placement for patients with different soft tissue phenotypes.

International assessment of inter- and intrarater reliability of the International Frontal Sinus Anatomy Classification system.

BACKGROUND: Inconsistencies in the nomenclature of structures of the frontal sinus have impeded the development of a validated "reference standard" classification system that surgeons can reliably agree upon. The International Frontal Sinus Anatomy Classification (IFAC) system was developed as a consensus document, based on expert opinion, attempting to address this issue. The purposes of this study are to: establish the reliability of the IFAC as a tool for classifying cells in the frontal recess among an international group of rhinologists; and improve communication and teaching of frontal endoscopic sinus surgery (ESS). METHODS: Forty-two computed tomography (CT) scans, each with a marked frontal cell, were reviewed by 15 international fellowship-trained rhinologists. Each marked cell was classified into 1 of 7 categories described in the IFAC, on 2 occasions separated by 2 weeks. Inter- and intrarater reliability were evaluated using Light's kappa (κ), the interclass correlation coefficient (ICC), and simple proportion of agreement. RESULTS: Interrater reliability showed pairwise κ values ranging from 0.7248 to 1.0, with a mean of 0.9162 (SD, 0.0537). The ICC was 0.98. Intrarater reliability showed κ values ranging from 0.8613 to 1.0, with a mean of 0.9407 (SD, 0.0376). The within-rater ICC was 0.98. CONCLUSION: Among a diverse sample of rhinologists (raters), there was substantial to almost perfect agreement between raters, and among individual raters at different timepoints. The IFAC is a reliable tool for classification of cells in the frontal sinus. Further outcome studies are still needed to determine the validity of the IFAC.

Construct validity of a low-cost medium-fidelity endoscopic sinus surgery simulation model.

OBJECTIVE: Assess construct validity of a low-cost medium-fidelity silicone injection molded model task trainer for endoscopic sinus surgery (ESS) training. METHODS: Fellowship-trained rhinologists, otolaryngology attendings, and otolaryngology residents at various levels of training performed sinus endoscopy and seven procedures on the model. Construct validity was evaluated by comparing novice to various levels of experienced performance using a validated checklist. RESULTS: Thirty-two subjects participated in this study. Otolaryngology attendings and postgraduate year (PGY) 3 to 5 otolaryngology residents significantly outperformed PGY 1 to 2 otolaryngology residents on most tasks in the task-specific checklist. CONCLUSIONS: This study demonstrated the construct validity of the low-cost medium-fidelity ESS model. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1505-1509, 2019.

VARIABILITY IN THYROID CANCER MANAGEMENT AND PROGNOSIS AMONG HISPANIC VERSUS NON-HISPANIC PATIENTS : 17 YEARS DATA FROM UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AND UNIVERSITY HEALTH SYSTEM AT SAN ANTONIO.

Abstracts: Objective : Given the increase in the incidence of thyroid cancer in the United States, and it's potential public health implications, patient studies assessing ethnic, disparity and health care access are important. In this study, we retrospectively examined the variability in stage of thyroid cancer at presentation and final outcome among Hispanic vs non-Hispanic patients. METHOD: After obtaining IRB approval, we retrospectively reviewed the medical records of 220 adult patients with papillary thyroid carcinoma(PTC) who were treated at UT Health Science Center San Antonio between1996 and 2013. At disease presentation, patients were staged and risk stratified according to the 2009 American Thyroid Association (ATA) and TNM staging system. Clinical data obtained during the first 6-18 months was used to identify the initial response to therapy and clinical data from the last follow up visit was used to identify the "final" outcome. We examined the effect of insurance and ethnicity on initial response to therapy and final outcome using Chi-square test and one way ANOVA. RESULT: Our patient population's ATA risk at diagnosis, initial response to therapy and final outcome did not differ by ethnicity (P=0.5, 0.3 &0.4) and insurance coverage(P=0.7, 0.3 & 0.4) . CONCLUSION: Insurance coverage and ethnicity may not be independent factors since ethnic minority individuals are more likely to be uninsured.

Adaptive response in mouse bone marrow stromal cells exposed to 900MHz radiofrequency fields: Impact of poly (ADP-ribose) polymerase (PARP).

This study examined whether non-ionizing radiofrequency fields (RF) exposure is capable of inducing poly (ADP-ribose) polymerase-1 (PARP-1) in bone marrow stromal cells (BMSCs) and whether it plays a role in RF-induced adaptive response (AR). Bone marrow stromal cells (BMSCs) were exposed to 900MHz RF at 120µW/cm2 power flux density for 3h/day for 5days and then challenged with a genotoxic dose of 1.5Gy gamma-radiation (GR). Some cells were also treated with 3-aminobenzamide (3-AB, 2mM final concentration), a potent inhibitor of PARP-1. Un-exposed and sham (SH)-exposed control cells as well as positive control cells exposed to gamma radiation (GR) were included in the experiments. The expression of PARP-1 mRNA and its protein levels as well as single strand breaks in the DNA and the kinetics of their repair were evaluated at several times after exposures. The results indicated the following. (a) Cells exposed to RF alone showed significantly increased PARP-1 mRNA expression and its protein levels compared with those exposed to SH- and GR alone. (b) Treatment of RF-exposed cells with 3-AB had diminished such increase in PARP-1. (c) Cells exposed to RF+GR showed significantly decreased genetic damage as well as faster kinetics of repair compared with those exposed to GR alone. (d) Cells exposed to RF+3-AB+GR showed no such decrease in genetic damage. Thus, the overall date suggested that non-ionizing RF exposure was capable of inducing PARP-1 which has a role in RF-induced AR.

DNA double-strand breaks and micronuclei in human blood lymphocytes after repeated whole body exposures to 7T Magnetic Resonance Imaging.

PURPOSE: To examine the extent of genetic damage, assessed from deoxyribonucleic acid (DNA) double-strand breaks (DSBs) and micronuclei (MN) in peripheral blood mononuclear cells obtained from individuals repeatedly exposed to 7T Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: The study protocol was approved by the local ethics committee. Informed consent was obtained from 22 healthy, non-smoking, non-alcoholic male individuals, who had never undergone radio-/chemo-therapy, scintigraphy, and had not undergone X-ray examination one year prior blood withdrawal. Eleven participants were repeatedly exposed to 7T and 3T MRI while working with/around scanners or frequently participating as 7T and lower field MRI research subjects (mean age 34±7years). The other half was never exposed to 7T or lower field MRI and served as controls (mean age 33±9years). The damage in lymphocytes was assessed using anti-γH2AX immunofluorescence staining of DNA DSBs and by quantification of MN. Isolated cells were further exposed in vitro to 7T MRI either alone or in the presence of the DNA damaging drug etoposide, to determine if there is any additional combined effect. The kinetics of DNA damage repair were examined. RESULTS: The mean base-level of γH2AX foci/cell and incidence of MN between repeatedly exposed and control group were not significantly different (P=0.618 and P=0.535, respectively). The additional in vitro exposure of cells to 7T MRI had no significant impact on MN frequencies and γH2AX foci at 1, 20 and 72h after exposure. CONCLUSION: Frequently repeated 7T MRI exposure did not result in a detectable increase in genotoxicity indices and alterations of DNA repair kinetics.

Mobile phones, non-ionizing radiofrequency fields and brain cancer: is there an adaptive response?

There is widespread concern among the general public regarding the ever increasing use of mobile phones. The concern is mainly because the antenna which transmits nonionizing radiofrequency fields is held close to the head during use and thus might cause brain cancer. By far, the largest epidemiological study was conducted by the INTER-PHONE study group and the results were published in 2011. The author's conclusions were (i) no increased risk of meningioma and glioma in mobile phone users and (ii) there were suggestions of an increased risk for glioma at the highest exposure levels but, bias and error prevented a causal interpretation. We have carefully examined all of the odd ratios presented in the INTERPHONE study publication: our results showed 24.3% decreased and 0.7% increased risk for meningioma and 22.1% decreased and 6.6% increased risk for glioma. Hence, we hypothesize that the overwhelming evidence for the decreased risk for both diseases may be due to the induction of 'adaptive response' which is well-documented in scientific literature.

The frequency of herpes simplex virus changes in anal Pap smear and its association with squamous intraepithelial lesions in high-risk male patients.

While there are studies postulating a model of synergism between human papillomavirus (HPV) and herpes simplex virus (HSV) in cervical carcinogenesis, the frequency of anal herpes as well as its association with anal squamous intraepithelial lesions (ASILs) has been understudied in men. This study evaluates the frequency of HSV changes in anal Pap smears and its association with ASILs in a high-risk population. A computerized search for specimens associated with anal cytology that had positive findings of HSV was performed. The electronic medical records were examined for past diagnosis of herpes, HSV serology prior to or after cytology, and if the patient received treatment after cytologic diagnosis of HSV. Of the 470 anal Pap smears (Thin-prep) examined, seven had cellular changes consistent with HSV infection. All patients were asymptomatic human immunodeficiency virus (HIV) positive males with no prior HSV serology tests. Two patients had prior diagnoses of HSV infection. Cytologic abnormalities were identified in 86% ranging from atypical squamous cells of undetermined significance to high grade squamous intraepithelial lesion. Three patients were treated after the HSV cytologic diagnosis. The frequency of HSV changes in anal Pap smear is low (1.48%), but the presence of concomitant cytologic abnormalities is high (86%). While our findings suggest the possible role of HSV as a HPV co-factor in ASILs, larger studies are needed to support this. Identification of HSV infection on anal Pap smear is important for institution of patient treatment and subsequent reduction of transmission.

Identifying DNA mutations in purified hematopoietic stem/progenitor cells.

In recent years, it has become apparent that genomic instability is tightly related to many developmental disorders, cancers, and aging. Given that stem cells are responsible for ensuring tissue homeostasis and repair throughout life, it is reasonable to hypothesize that the stem cell population is critical for preserving genomic integrity of tissues. Therefore, significant interest has arisen in assessing the impact of endogenous and environmental factors on genomic integrity in stem cells and their progeny, aiming to understand the etiology of stem-cell based diseases. LacI transgenic mice carry a recoverable λ phage vector encoding the LacI reporter system, in which the LacI gene serves as the mutation reporter. The result of a mutated LacI gene is the production of ß-galactosidase that cleaves a chromogenic substrate, turning it blue. The LacI reporter system is carried in all cells, including stem/progenitor cells and can easily be recovered and used to subsequently infect E. coli. After incubating infected E. coli on agarose that contains the correct substrate, plaques can be scored; blue plaques indicate a mutant LacI gene, while clear plaques harbor wild-type. The frequency of blue (among clear) plaques indicates the mutant frequency in the original cell population the DNA was extracted from. Sequencing the mutant LacI gene will show the location of the mutations in the gene and the type of mutation. The LacI transgenic mouse model is well-established as an in vivo mutagenesis assay. Moreover, the mice and the reagents for the assay are commercially available. Here we describe in detail how this model can be adapted to measure the frequency of spontaneously occurring DNA mutants in stem cell-enriched Lin(-)IL7R(-)Sca-1(+)cKit(++)(LSK) cells and other subpopulations of the hematopoietic system.

Genetic damage in human cells exposed to non-ionizing radiofrequency fields: a meta-analysis of the data from 88 publications (1990-2011).

Based on the 'limited' evidence suggesting an association between exposure to radiofrequency fields (RF) emitted from mobile phones and two types of brain cancer, glioma and acoustic neuroma, the International Agency for Research on Cancer has classified RF as 'possibly carcinogenic to humans' in group 2B. In view of this classification and the positive correlation between increased genetic damage and carcinogenesis, a meta-analysis was conducted to determine whether a significant increase in genetic damage in human cells exposed to RF provides a potential mechanism for its carcinogenic potential. The extent of genetic damage in human cells, assessed from various end-points, viz., single-/double-strand breaks in the DNA, incidence of chromosomal aberrations, micronuclei and sister chromatid exchanges, reported in a total of 88 peer-reviewed scientific publications during 1990-2011 was considered in the meta-analysis. Among the several variables in the experimental protocols used, the influence of five specific variables related to RF exposure characteristics was investigated: (i) frequency, (ii) specific absorption rate, (iii) exposure as continuous wave, pulsed wave and occupationally exposed/mobile phone users, (iv) duration of exposure, and (v) different cell types. The data indicated the following. (1) The magnitude of difference between RF-exposed and sham-/un-exposed controls was small with some exceptions. (2) In certain RF exposure conditions there was a statistically significant increase in genotoxicity assessed from some end-points: the effect was observed in studies with small sample size and was largely influenced by publication bias. Studies conducted within the generally recommended RF exposure guidelines showed a smaller effect. (3) The multiple regression analyses and heterogeneity goodness of fit data indicated that factors other than the above five variables as well as the quality of publications have contributed to the overall results. (4) More importantly, the mean indices for chromosomal aberrations, micronuclei and sister chromatid exchange end-points in RF-exposed and sham-/un-exposed controls were within the spontaneous levels reported in a large data-base. Thus, the classification of RF as possibly carcinogenic to humans in group 2B was not supported by genotoxicity-based mechanistic evidence.

Predictive value of Sp1/Sp3/FLIP signature for prostate cancer recurrence.

Prediction of prostate cancer prognosis is challenging and predictive biomarkers of recurrence remain elusive. Although prostate specific antigen (PSA) has high sensitivity (90%) at a PSA level of 4.0 ng/mL, its low specificity leads to many false positive results and considerable overtreatment of patients and its performance at lower ranges is poor. Given the histopathological and molecular heterogeneity of prostate cancer, we propose that a panel of markers will be a better tool than a single marker. We tested a panel of markers composed of the anti-apoptotic protein FLIP and its transcriptional regulators Sp1 and Sp3 using prostate tissues from 64 patients with recurrent and non-recurrent cancer who underwent radical prostatectomy as primary treatment for prostate cancer and were followed with PSA measurements for at least 5 years. Immunohistochemical staining for Sp1, Sp3, and FLIP was performed on these tissues and scored based on the proportion and intensity of staining. The predictive value of the FLIP/Sp1/Sp3 signature for clinical outcome (recurrence vs. non-recurrence) was explored with logistic regression, and combinations of FLIP/Sp1/Sp3 and Gleason score were analyzed with a stepwise (backward and forward) logistic model. The discrimination of the markers was identified by sensitivity-specificity analysis and the diagnostic value of FLIP/Sp1/Sp3 was determined using area under the curve (AUC) for receiver operator characteristic curves. The AUCs for FLIP, Sp1, Sp3, and Gleason score for predicting PSA failure and non-failure were 0.71, 0.66, 0.68, and 0.76, respectively. However, this increased to 0.93 when combined. Thus, the "biomarker signature" of FLIP/Sp1/Sp3 combined with Gleason score predicted disease recurrence and stratified patients who are likely to benefit from more aggressive treatment.

Pathologic changes in breast cancer after anti-estrogen therapy.

Breast cancer patients do not commonly receive anti-estrogens prior to surgical excision. We reviewed a cohort of patients who received preoperative anti-estrogen therapy after baseline biopsy and then had a repeat biopsy after several weeks on treatment. Patients with estrogen receptor positive tumors received anastrozole and fulvestrant in combination with gefitinib. Core needle biopsies were performed at day 1 and 21, and tumors were completely excised if operable at day 112. All patients were postmenopausal. Following treatment, tumors had degenerative changes including smudged nuclei, decreased nuclear size, intranuclear vacuoles, vacuolated cytoplasm, and increased cellular discohesion. In addition, increased tubule formation and intracytoplasmic lumina were seen in 6/9 cases (66.7%) and decreased mitotic rate was demonstrated in 7/9 cases (77.8%). These findings indicate increased differentiation of the tumor cells in response to anti-estrogen therapy and that may correlate with clinical response.

Evaluation of napsin A, cytokeratin 5/6, p63, and thyroid transcription factor 1 in adenocarcinoma versus squamous cell carcinoma of the lung.

CONTEXT: The distinction of lung adenocarcinoma from other types of primary lung malignancies is important clinically. Accurate morphologic classification is often hindered because 70% of lung cancers are diagnosed on limited fine-needle aspiration or transbronchial biopsy specimens. Although thyroid transcription factor 1 (TTF-1) has historically been the most specific marker for lung adenocarcinoma, a relatively new marker, napsin A, has recently been shown to be more sensitive and specific than TTF-1. OBJECTIVE: To find the most cost-effective panel to reliably distinguish lung adenocarcinoma from squamous cell carcinoma. DESIGN: A total of 291 lung cancers were evaluated morphologically (197 adenocarcinomas [75%]; 66 squamous cell carcinomas [25%]; 28 cases could not be classified into either and were dropped). Immunohistochemistry for napsin A, Cytokeratin 5/6, p63, and TTF-1 was performed on a formalin-fixed tissue microarray obtained from Toyama, Japan. Cases were scored as positive or negative against a negative control. RESULTS: Napsin A had 83% sensitivity and 98% specificity and TTF-1 had 60% sensitivity and 98% specificity for adenocarcinoma. Cytokeratin 5/6 had 53% sensitivity and 96% specificity and p63 had 95% sensitivity and 86% specificity for squamous cell carcinoma. A panel of napsin A and p63 has a specificity of 94% and a sensitivity of 96% for distinguishing adenocarcinoma from squamous cell carcinoma. CONCLUSIONS: The source of the antibody is important in avoiding false-negative results. The most cost-effective tissue-preserving panel for small biopsy specimens in the differential diagnosis of lung adenocarcinoma versus squamous cell carcinoma is a combination of p63 and napsin A.

Diabetes and risk of renal cell carcinoma.

BACKGROUND AND OBJECTIVES: There is evidence that the incidence of solid tumors is markedly increased in patients with diabetes mellitus. In the current study, we investigate the association between diabetes and renal cancer. PATIENTS AND METHODS: A single-center retrospective analysis of 473 patients who underwent nephrectomy for renal cell carcinoma (RCC) was performed. Diabetic RCC patients were screened for age, gender, ethnicity, HgA1C, glucose levels and renal function. RESULTS: Of the 473 cases with RCC, we identified 120 patients (25.4%) with a history of diabetes. The incidence of diabetes in RCC patients was higher in female than male subjects and in Hispanic compared to White and Other ethnic backgrounds. At diagnosis, the majority of diabetic RCC patients were 50-59 years of age. In diabetic RCC cases, clear cell type histology (92.0%), nuclear grade 2 (56.1%) and tumor size range from 1-5 cm (65.7%) were the most common in each category. CONCLUSION: Our findings indicate that diabetic RCC patients have a predominance of localized, small clear cell RCC. In addition, females with a history of RCC have a higher frequency of diabetes compared to males. This is the first report of clinical and histopathological features of RCC associated with diabetes.

Chemoradionuclide therapy with 186Re-labeled liposomal doxorubicin in combination with radiofrequency ablation for effective treatment of head and neck cancer in a nude rat tumor xenograft model.

PURPOSE: To determine the therapeutic efficacy of rhenium 186 ((186)Re)-labeled PEGylated liposomal doxorubicin ((186)Re-liposomal doxorubicin) in combination with radiofrequency (RF) ablation of human head and neck squamous cell carcinoma (HNSCC) xenograft in nude rats. MATERIALS AND METHODS: This investigation was approved by the animal care committee. Sixty nude rats with subcutaneously implanted HNSCC xenografts (six per group) were treated with (a) RF ablation (70 °C for 5 minutes), (b) PEGylated liposomes, (c) liposomal doxorubicin, (d) (186)Re-PEGylated liposomes (1295 MBq/kg), (e) (186)Re-liposomal doxorubicin (555 MBq/kg), (f) PEGylated liposomes plus RF ablation, (g) liposomal doxorubicin plus RF ablation, (h) (186)Re-PEGylated liposomes plus RF ablation, or (i) (186)Re-liposomal doxorubicin plus RF ablation. Six rats did not receive any treatment (control group). Tumor uptake in (186)Re therapy groups was monitored with small-animal single photon emission computed tomography for 5 days. Therapeutic efficacy was monitored for 6 weeks with measurement of tumor volume, calculation of the percentage injected dose of fluorine 18 fluorodeoxyglucose (FDG) in tumor from small-animal positron emission tomography (PET) images, and determination of viable tumor volume at histopathologic examination. Significant differences between groups were determined with analysis of variance. RESULTS: The average tumor volume (± standard deviation) on the day of therapy was 1.32 cm(3) ± 0.17. At 6 weeks after therapy, control of tumor growth was better with (186)Re-liposomal doxorubicin than with liposomal doxorubicin alone (tumor volume, 2.26 cm(3) ± 0.89 vs 5.43 cm(3) ± 0.93, respectively; P < .01). The use of RF ablation with liposomal doxorubicin and (186)Re-liposomal doxorubicin further improved tumor control (tumor volume, 2.05 cm(3) ± 1.36 and 1.49 cm(3) ± 1.47, respectively). The tumor growth trend correlated with change in percentage of injected dose of FDG in tumor for all groups (R(2) = 0.85, P < .001). Viable tumor volume was significantly decreased in the group treated with (186)Re-liposomal doxorubicin plus RF ablation (0.54 cm(3) ± 0.38; P < .001 vs all groups except (186)Re-liposomal doxorubicin alone). CONCLUSION: Triple and dual therapies had an observable trend ((186)Re-liposomal doxorubicin plus RF ablation > (186)Re-liposomal doxorubicin > liposomal doxorubicin plus RF ablation > liposomal doxorubicin) of improved tumor growth control and decreased viable tumor compared with other therapies. FDG PET could be used as a noninvasive surrogate marker for tumor growth and viability in this tumor model.

Predicting hypocalcemia after total thyroidectomy: parathyroid hormone level vs. serial calcium levels.

A 24- to 48-hour in-hospital observation period to monitor for hypocalcemia is common after total thyroidectomy. Because most thyroidectomy patients do not experience this potentially serious complication, investigators have searched for methods and clinical indicators that may help stratify thyroidectomy patients according to their risk of developing hypocalcemia and identify those who can be safely discharged earlier. We conducted a retrospective study to compare the value of an immediate postoperative intact parathyroid hormone (PTH) level and serial calcium levels in predicting the development of hypocalcemia following total thyroidectomy. Our study population was made up of 69 consecutive patients who had undergone total thyroidectomy from January 2004 through March 2005. These patients were divided into two groups on the basis of their postoperative calcium levels; 11 patients (16%) had developed transient hypocalcemia (serum calcium level: <7.5 mg/dl) and 58 (84%) had remained normocalcemic. A model was developed to assess the relationship between early (<60 min) postoperative PTH levels and serial (6 and 18 hr) calcium levels, and the two-sample Student t test was used to identify differences between the two groups. Analysis showed that hypocalcemia was associated with a postoperative PTH level of less than 14 pg/ml and a negative serum calcium slope between 6 and 18 hours postoperatively. A single early postoperative intact PTH measurement may be the most cost-effective screening tool for hypocalcemia, but even greater specificity can be achieved by combining those findings with a serum calcium measurement taken 6 hours postoperatively. The combination of the two measurements represents the safest method of assessing risk and identifying those patients who can be discharged on the day of surgery.

Effects of tuberculosis, race, and human gene SLCO1B1 polymorphisms on rifampin concentrations.

Rifampin has concentration-dependent activity against Mycobacterium tuberculosis. However, marked intersubject variation of rifampin concentrations occurs. In this study, we evaluated rifampin pharmacokinetics in relation to tuberculosis, geographic region, race, and single nucleotide polymorphisms of the human transporter genes SLCO1B1, SLCO1B3, and MDR1. Seventy-two adults with pulmonary tuberculosis from Africa, North America, and Spain were evaluated during multidrug intensive-phase therapy, and their results were compared to those from 16 healthy controls from North America. Rifampin pharmacokinetic values were similar between tuberculosis patients and controls (geometric mean [GM] area under the concentration-time curve from 0 to 24 h [AUC(0-24)] of 40.2 versus 40.9 µg.h/ml; P = 0.9). However, in multivariable analyses, the rifampin AUC(0-24) was significantly affected by rifampin dosage (in mg/kg of body weight), polymorphisms in the SLCO1B1 gene, and the presence of tuberculosis by geographic region. The adjusted rifampin AUC(0-24) was lowest in patients with tuberculosis from Africa compared to that in non-African patients or control subjects. The adjusted rifampin AUC(0-24) was also 36% lower among participants with SLCO1B1 genotype c.463CA than that among participants with SLCO1B1 genotype c.463CC (adjusted GM, 29.8 versus 46.7 µg.h/ml; P = 0.001). Polymorphisms in the SLCO1B1 gene associated with lower rifampin exposure were more frequent among black subjects. In conclusion, marked intersubject variation of the rifampin AUC(0-24) values was observed, but the mean values of the AUC(0-24) did not significantly vary between patients with tuberculosis and healthy controls. Lower rifampin exposure was associated with the polymorphism of the SLCO1B1 c.463C>A gene. When adjusted for the patient mg/kg dosage and transporter gene polymorphisms, rifampin exposure was lower in patients with tuberculosis, which suggests that additional absorption or metabolic processes affect rifampin exposure with tuberculosis disease.

Micronuclei in the blood and bone marrow cells of mice exposed to specific complex time-varying pulsed magnetic fields.

For 8 weeks, adult CD-1 male mice were continuously exposed to complex time-varying pulsed magnetic fields (PMF) generated in the horizontal direction by a set of square Helmholtz coils. The PMF were <1000 Hz and delivered at a peak flux density of 1 mT. Sham-exposed mice were kept in a similar exposure system without a PMF. Positive control animals exposed to 1 Gy gamma radiation were also included in the study. Blood samples were collected before (time 0) and at 2, 4, 6, and 8 weeks. All mice were euthanized at the end of 8 weeks and their bone marrow was collected. From each blood and bone marrow sample, smears were prepared on microscope slides, fixed in absolute methanol, air-dried, and stained with acridine orange. All slides were coded and examined using a fluorescence microscope. The extent of genotoxicity and cytotoxicity was assessed from the incidence of micronuclei (MN) and percent polychromatic erythrocytes (PCE) in the blood and bone marrow, respectively. The data indicated that both indices in PMF-exposed mice were not significantly different from those observed in sham-exposed animals. In contrast, positive control mice exhibited significantly increased MN, and decreased percentages of PCE in both tissues. Thus, the overall data suggested that 8 weeks of continuous exposure to PMF did not induce significantly increased genotoxicity and cytotoxicity in experimental mice. Further investigations are underway using other genotoxicity assays (comet assay, gamma-H2AX foci, and chromosomal aberrations) to assess genotoxicity following PMF exposure.