Potential Modifying Effect of the APOEε4 Allele on Age of Onset and Clinical Manifestations in Patients with Early-Onset Alzheimer's Disease with and without a Pathogenic Variant in PSEN1 in a Sample of the Mexican Population.

In Alzheimer's disease (AD), the age of onset (AoO) exhibits considerable variability, spanning from 40 to 90 years. Specifically, individuals diagnosed with AD and exhibiting symptoms prior to the age of 65 are typically classified as early onset (EOAD) cases. Notably, the apolipoprotein E (APOE) ε4 allele represents the most extensively studied genetic risk factor associated with AD. We clinically characterized and genotyped the APOEε4 allele from 101 individuals with a diagnosis of EOAD, and 69 of them were affected carriers of the autosomal dominant fully penetrant PSEN1 variant c.1292C>A (rs63750083, A431E) (PSEN1+ group), while there were 32 patients in which the genetic cause was unknown (PSEN1- group). We found a correlation between the AoO and the APOEε4 allele; patients carrying at least one APOEε4 allele showed delays, in AoO in patients in the PSEN1+ and PSEN1- groups, of 3.9 (p = 0.001) and 8.6 years (p = 0.012), respectively. The PSEN1+ group presented higher frequencies of gait disorders compared to PSEN1- group, and apraxia was more frequent with PSEN1+/APOE4+ than in the rest of the subgroup. This study shows what appears to be an inverse effect of APOEε4 in EOAD patients, as it delays AoO and modifies clinical manifestations.

Extracranial midline defects in a patient with craniofrontonasal syndrome with a novel EFNB1 mutation.

We report a female patient with craniofrontonasal syndrome (CFNS) who in addition showed other cranial and extracranial midline defects including partial corpus callosum agenesis, ocular melanocytosis, pigmentary glaucoma, duplex collecting system, uterus didelphys, and septate vagina. She was found to have a novel pathogenic variant in exon 5 of EFNB1, c.646G>T (p.Glu216*) predicted to cause premature protein truncation. From our review, we found at least 39 published CFNS patients with extracranial midline defects, comprising congenital diaphragmatic hernia, congenital heart defects, umbilical hernia, hypospadias, and less frequently, sacrococcygeal teratomas, and internal genital anomalies in females. These findings support that the EFNB1 mutations have systemic consequences disrupting morphogenetic events at the extracranial midline. Though these are not rigorously included as midline defects, we found at least 10 CFNS patients with congenital anomalies of the kidney and urinary tract, all females. Additionally, uterus didelphys and ocular melanocytosis observed in our patient are proposed also as a previously unreported EFNB1-related midline defects. In addition, this case may be useful for considering the intentional search for genitourinary anomalies in future patients with CFNS, which will be helpful to define their frequency in this entity.

Nursing students' perceptions of peer learning through cross-cultural student-led webinars: A qualitative study.

AIMS: To explore nursing students' perception of peer learning during cross-cultural learning activities through student-led webinars. DESIGN: An exploratory qualitative study. METHODS: Thematic analysis of data collected from reflective journals and focus-group interviews of participating nursing students across three international universities in Australia, Hong Kong, and Sweden during autumn 2017. RESULTS: Three themes were identified: peer learning as creation of friendship; peer learning from interactions that went beyond what was originally intended; and peer learning as empowered learning. CONCLUSION: Combining peer learning as an educational approach with cross-cultural and student-led webinars provided new perspectives. On-line learning across global boundaries, based on a sound educational model, creates new opportunities for internationalization without straining individual and institutional financial resources.

Genetic variants of mucins: unexplored conundrum.

Alternative gene splicing, occurring ubiquitously in multicellular organisms can produce several protein isoforms with putatively different functions. The enormously extended genomic structure of mucin genes characterized by the presence of multiple exons encoding various domains may result in functionally diverse repertoire of mucin proteins due to alternative splicing. Splice variants (Svs) and mutations in mucin genes have been observed in various cancers and shown to participate in cancer progression and metastasis. Although several mucin Svs have been identified, their potential functions remain largely unexplored with the exception of the Svs of MUC1 and MUC4. A few studies have examined the expression of MUC1 and MUC4 Svs in cancer and indicated their potential involvement in promoting cancer cell proliferation, invasion, migration, angiogenesis and inflammation. Herein we review the current understanding of mucin Svs in cancer and inflammation and discuss the potential impact of splicing in generating a functionally diverse repertoire of mucin gene products. We also performed mutational analysis of mucin genes across five major cancer types in International Cancer Genome Consortium database and found unequal mutational rates across the panel of cancer-associated mucins. Although the functional role of mucins in the pathobiology of various malignancies and their utility as diagnostic and therapeutic targets remain undisputed, these attributes need to be reevaluated in light of the potentially unique functions of disease-specific genetic variants of mucins. Thus, the expressional and functional characterization of the genetic variants of mucins may provide avenues to fully exploit their potential as novel biomarkers and therapeutic targets.

Neutralization of SARS-CoV-2 and Intranasal Protection of Mice with a nanoCLAMP Antibody Mimetic.

Intranasal treatment, combined with vaccination, has the potential to slow mutational evolution of viruses by reducing transmission and replication. Here, we illustrate the development of a SARS-CoV-2 receptor-binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope-binding nanoCLAMP, P2609. The resulting multimerized nanoCLAMP P2712 had sub-pM affinity for the Wuhan and South African (B.1.351) RBD (KD < 1 pM) and decreasing affinity for the Delta (B.1.617.2) and Omicron (B.1.1.529) variants (86 pM and 19.7 nM, respectively). P2712 potently inhibited the ACE2:RBD interaction, suggesting its utility as a therapeutic. With an IC50 = 0.4 ± 0.1 nM obtained from neutralization experiments using pseudoviral particles, nanoCLAMP P2712 protected K18-hACE2 mice from SARS-CoV-2 infection, reduced viral loads in the lungs and brains, and reduced associated upregulation of inflammatory cytokines and chemokines. Together, our findings warrant further investigation into the development of nanoCLAMPs as effective intranasally delivered COVID-19 therapeutics.

Evaluation of a combined blood glucose monitoring and gaming system (Didget®) for motivation in children, adolescents, and young adults with type 1 diabetes.

The purpose of this study was to assess the performance and acceptability of a blood glucose meter coupled with a gaming system for children, adolescents, and young adults with type 1 diabetes. During an in-clinic visit, duplicate blood samples were tested by subjects (N = 147; aged 5-24 yr) and health care providers (HCPs) to evaluate the accuracy and precision of the Didget® system. Subjects' meter results were compared against Yellow Springs Instruments (YSI) reference results and HCP results using least squares regression and error grid analyses. Precision was measured by average within-subject and within-HCP coefficient of variation (CV). During the home-use component of this study, subjects (n = 58) tested their blood glucose at least two to three times daily for 3-5 d to evaluate routine use of the system. Subjects' meter results showed significant correlations with both YSI (r(2) = 0.94; p < 0.001 for regression slope) and HCP results (r(2) = 0.96; p < 0.001). Average within-subject and within-HCP CVs were 5.9 and 7.2%, respectively. Overall satisfaction was assessed by subjects, their parents or guardians, and HCP surveys. Subject satisfaction with the Didget® system was good to excellent; most subjects found the system easy to use, motivating, and helpful for building good blood glucose monitoring habits. Most HCPs agreed that the system fulfilled a need in diabetes management. In conclusion, the Didget® system was precise and clinically accurate in the hands of children, adolescents, and young adults with type 1 diabetes.

Analysis of In Vitro Leukocyte Responses to Biomaterials in the Presence of Antimicrobial Porcine Neutrophil Extract (AMPNE).

Implant insertion can evoke excessive inflammation which disrupts the healing process and potentially leads to complications such as implant rejection. Neutrophils and macrophages play a vital role in the early inflammatory phase of tissue repair, necessitating the study of cellular responses in host-implant interactions. In order to deepen the knowledge about these interactions, the response of neutrophils and macrophages to contact with selected biomaterials was examined in vitro on the basis of secretory response as well as reactive oxygen species/reactive nitrogen species (ROS/RNS) generation. Porcine neutrophils exposed to hydroxyapatite (HA) released more enzymes and generated higher levels of ROS/RNS compared to the control group. The addition of AMPNE diminished these responses. Although the results from porcine cells can provide valuable preliminary data, further validation using human cells or clinical studies would be necessary to fully extrapolate the findings to human medicine. Our study revealed that human neutrophils after contact of with HA increased the production of nitric oxide (NO) (10.00 ± 0.08 vs. control group 3.0 ± 0.11 µM, p < 0.05), while HAP or FAP did not elicit a significant response. Human macrophages cultured with HA produced more superoxide and NO, while HAP or FAP had a minimal effect, and curdlan reduced ROS/RNS generation. The addition of AMPNE to cultures with all biomaterials, except curdlan, reduced neutrophil activity, regardless of the peptides' origin. These results highlight the potential of antimicrobial peptides in modulating excessive biomaterial/host cell reactions involving neutrophils and macrophages, enhancing our understanding of immune reactions, and suggesting that AMPNE could regulate leukocyte response during implantation.

Native Pig Neutrophil Products: Insights into Their Antimicrobial Activity.

Cationic antimicrobial peptides are molecules with potential applications for treating infections due to their antimicrobial and immunomodulatory properties. The aim of this work was to explore the antimicrobial activity and mechanisms of action of a porcine neutrophil cathelicidin mixture (MPPN). Gram-positive and Gram-negative bacteria were used to determine the minimum inhibitory concentration (MIC) and experiments of both time-kill kinetics and effects on growth curves were performed. Planar black lipid bilayer conductance was measured to analyze the interaction of MPPN with lipid bilayers. Visualization of bacterial surfaces and membrane alterations was achieved using atomic force microscopy and transmission electron microscopy. The effects on the activity of efflux pumps (EPs) were studied with an intracellular accumulation of acridine orange (AO) assay. In E. coli, MPPN behaves as a bactericide at high concentrations and as a bacteriostatic at lower concentrations. The bacteriostatic effect was also observed for slightly shorter periods in S. enterica. The mixture was not active on S. aureus. The increase in AO accumulation in the presence of MPPN indicates that, at least in E. coli, the mixture causes inhibition of the EP function. Observed and detected variable conductance events demonstrate a strong MPPN effect on lipid bilayers. Damage to the structure of treated E. coli indicates that MPPN induces alterations in the bacterial surface. The use of AMPs capable of inhibiting EP can be seen as a good tool to combat antimicrobial resistance since they could be used alone or in combination with other conventional antibiotics to which bacteria have become resistant.

Genetic analysis of TMPRSS6 catalytic domain variants in Mexican patients with iron treatment refractoriness.

OBJECTIVE: To identify the TMPRSS6 gene variants in Mexican patients with iron treatment refractoriness, to describe hematological and iron profile parameters, and to use bioinformatic prediction and protein modeling tools to assess a possible biological impact for the detected missense variants. METHODS: Nineteen patients referred with iron treatment refractoriness were studied. Peripheral blood was collected to determine hematic cytometry, iron profile, hemoglobin electrophoresis, and quantification. Molecular screening was carried out for exons 15 through 18 of the TMPRSS6 gene by Sanger sequencing and for frequent thalassemia variants by amplification-refractory mutation system-polymerase chain reaction (PCR) and gap-PCR. The biological impact of the detected missense variants was assessed using bioinformatic prediction and protein modeling tools. RESULTS: We found 5 genetic variants in the matriptase-2 catalytic domain: 1 at intron-15/exon-16 junction (rs60484081) and 4 exonic, 3 missense (rs377054987, p.Gly626Asp; rs1384127820, p.Ser672Thr; rs855791, p.Val727Ala) and 1 synonymous (rs2235321, p.Tyr730=), with frequencies ranging from 0.18 to 0.53. No significant differences were observed in the hematological parameters or iron profile, considering type and number of variants. Bioinformatic predictions suggested a possible biological impact only for rs377054987. CONCLUSIONS: The TMPRSS6 variants observed in Mexican patients with oral iron treatment refractoriness have high frequencies; nevertheless, their relationship with hematological and iron profile parameters needs further research. The possible biological impact for rs377054987 is due to size and amino acid hydrophobicity changes and hydrogen bond modifications.

AURKA Gene Variants rs1047972, and rs8173 Are Associated With Breast Cancer.

PURPOSE: Association between variants rs1047972 and rs8173 of the AURKA gene in healthy women and breast cancer (BC) in a Mexican population. METHODS: Genomic DNA samples from 409 healthy women and 572 patients with BC were analyzed for variants rs1047972 and rs8173 of the AURKA gene by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: TT genotype (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.22-5.11; p = 0.0015) and the T allele (OR, 1.16; 95% CI, 1.23-2.12; p = 0.0007) of the rs1047972 variant were associated as risk susceptibility for BC relative to the control group. Contrarily, the GG genotype (OR, 0.64; 95% CI, 0.43-0.94; p = 0.029) was associated as a protective factor of susceptibility of BC of the variant rs8173 of the AURKA gene. Differences were observed in the patients with BC who were carriers of the CT genotype of the rs1047972 variant with overweight, obesity, estrogen receptor-positive plus obesity, Ki-67 (≥ 20%) plus history familial positive of cancer; and for variant rs8173 the BC patients who were CG carriers and presented chemotherapy gastric toxicity, hormonal receptor positive plus chemotherapy gastric toxicity, and menopause status plus chemotherapy gastric toxicity (p < 0.05). Two common haplotypes were identified in the study groups: CG and TC genotypes, were associated as a protective and risk factor, respectively (p < 0.05). CONCLUSION: Variants rs1047972 and rs8173 of the AURKA gene and the TC haplotype were associated as risk susceptibility factors for BC in this population.

Incidental Finding of Tuberculosis During Evaluation for Delayed Wound Healing.

Cutaneous tuberculosis (TB) is an uncommon form of extrapulmonary TB that can be difficult to diagnose. The following case is about a 14-year-old female who was experiencing delayed wound healing after an incision and drainage of a chest wall abscess. A computed tomography scan of her chest obtained 2 months after the procedure revealed pulmonary findings consistent with TB. An acid-fast bacilli culture was obtained from the wound after the computed tomography scan was performed and was positive for Mycobacterium tuberculosis 8 weeks later. Although TB is relatively uncommon in the United States, it is more prevalent in the Republic of Korea where the patient lives and was evaluated. This case serves to illustrate the long history of challenges the military medical community has faced with TB and to remind providers to be cognizant about local common diseases when serving overseas and include these diagnoses in their differentials.

PODO447: a novel antibody to a tumor-restricted epitope on the cancer antigen podocalyxin.

BACKGROUND: The success of new targeted cancer therapies has been dependent on the identification of tumor-specific antigens. Podocalyxin (Podxl) is upregulated on tumors with high metastatic index and its presence is associated with poor outcome, thus emerging as an important prognostic and theragnostic marker in several human cancers. Moreover, in human tumor xenograft models, Podxl expression promotes tumor growth and metastasis. Although a promising target for immunotherapy, the expression of Podxl on normal vascular endothelia and kidney podocytes could hamper efforts to therapeutically target this molecule. Since pathways regulating post-translational modifications are frequently perturbed in cancer cells, we sought to produce novel anti-Podxl antibodies (Abs) that selectively recognize tumor-restricted glycoepitopes on the extracellular mucin domain of Podxl. METHODS: Splenic B cells were isolated from rabbits immunized with a Podxl-expressing human tumor cell line. Abs from these B cells were screened for potent reactivity to Podxl+ neoplastic cell lines but not Podxl+ primary endothelial cells. Transcripts encoding heavy and light chain variable regions from promising B cells were cloned and expressed as recombinant proteins. Tumor specificity was assessed using primary normal tissue and an ovarian cancer tissue microarray (TMA). Mapping of the tumor-restricted epitope was performed using enzyme-treated human tumor cell lines and a glycan array. RESULTS: One mAb (PODO447) showed strong reactivity with a variety of Podxl+ tumor cell lines but not with normal primary human tissue including Podxl+ kidney podocytes and most vascular endothelia. Screening of an ovarian carcinoma TMA (219 cases) revealed PODO447 reactivity with the majority of tumors, including 65% of the high-grade serous histotype. Subsequent biochemical analyses determined that PODO447 reacts with a highly unusual terminal N-acetylgalactosamine beta-1 (GalNAcß1) motif predominantly found on the Podxl protein core. Finally, Ab-drug conjugates showed specific efficacy in killing tumor cells in vitro. CONCLUSIONS: We have generated a novel and exquisitely tumor-restricted mAb, PODO447, that recognizes a glycoepitope on Podxl expressed at high levels by a variety of tumors including the majority of life-threatening high-grade serous ovarian tumors. Thus, tumor-restricted PODO447 exhibits the appropriate specificity for further development as a targeted immunotherapy.

FDPS cooperates with PTEN loss to promote prostate cancer progression through modulation of small GTPases/AKT axis.

Farnesyl diphosphate synthase (FDPS), a mevalonate pathway enzyme, is highly expressed in several cancers, including prostate cancer (PCa). To date, the mechanistic, functional, and clinical significance of FDPS in cancer remains unexplored. We evaluated the FDPS expression and its cancer-associated phenotypes using in vitro and in vivo methods in PTEN-deficient and sufficient human and mouse PCa cells and tumors. Interestingly, FDPS overexpression synergizes with PTEN deficiency in PTEN conditionally knockout mice (P < 0.05) and expressed significantly higher in human (P < 0.001) PCa tissues, cell lines, and murine tumoroids compared to respective controls. In silico analysis revealed that FDPS is associated with increasing Gleason score, PTEN functionally deficient status, and poor survival of PCa. Ectopic overexpression of FDPS promotes oncogenic phenotypes such as colony formation (P < 0.01) and proliferation (P < 0.01) through activation of AKT and ERK signaling by prenylating Rho A, Rho G, and CDC42 small GTPases. Of interest, knockdown of FDPS in PCa cells exhibits decreased colony growth and proliferation (P < 0.001) by modulating AKT and ERK pathways. Further, genetic and pharmacological inhibition of PI3K but not AKT reduced FDPS expression. Pharmacological targeting of FDPS by zoledronic acid (ZOL), which is already in clinics, exhibit reduced growth and clonogenicity of human and murine PCa cells (P < 0.01) and 3D tumoroids (P < 0.02) by disrupting AKT and ERK signaling through direct interference of small GTPases protein prenylation. Thus, FDPS plays an oncogenic role in PTEN-deficient PCa through GTPase/AKT axis. Identifying mevalonate pathway proteins could serve as a therapeutic target in PTEN dysregulated tumors.

Intracellular amyloid beta expression leads to dysregulation of the mitogen-activated protein kinase and bone morphogenetic protein-2 signaling axis.

Alzheimer's disease (AD) is a neurodegenerative syndrome classically depicted by the parenchymal accumulation of extracellular amyloid beta plaques. However, recent findings suggest intraneuronal amyloid beta (iAß1-42) accumulation precedes extracellular deposition. Furthermore, the pathologic increase in iAß1-42 has been implicated in dysregulation of cellular mechanisms critically important in axonal transport. Owing to neuronal cell polarity, retrograde and anterograde axonal transport are essential trafficking mechanism necessary to convey membrane bound neurotransmitters, neurotrophins, and endosomes between soma and synaptic interfaces. Although iAß1-42 disruption of axonal transport has been implicated in dysregulation of neuronal synaptic transmission, the role of iAß1-42 and its influence on signal transduction involving the mitogen-activated protein kinase (MAPK) and morphogenetic signaling axis are unknown. Our biochemical characterization of intracellular amyloid beta accumulation on MAPK and morphogenetic signaling have revealed increased iAß1-42 expression leads to significant reduction in ERK 1/2 phosphorylation and increased bone morphogenetic protein 2 dependent Smad 1/5/8 phosphorylation. Furthermore, rescue of iAß1-42 mediated attenuation of MAPK signaling can be accomplished with the small molecule PLX4032 as a downstream enhancer of the MAPK pathway. Consequently, our observations regarding the dysregulation of these gatekeepers of neuronal viability may have important implications in understanding the iAß1-42 mediated effects observed in AD.

Age-based and reproductive biology of the Pacific Longnose Parrotfish Hipposcarus longiceps from Guam.

The Pacific longnose parrotfish Hipposcarus longiceps (Valenciennes 1840) represents a prime fishery resource throughout much of the tropical Pacific. In this study, we sampled the species from the Guam commercial fishery market across five consecutive years to characterize reproductive and age-based demographic information imperative for informed fishery management. Compared with other parrotfishes, this species was found to be large-bodied, but has only a moderate life span of 10 + years. Hipposcarus longiceps was confirmed as a diandric protogynous hermaphrodite with highly sex-specific growth patterns and an overall mean asymptotic length of 434 mm fork length (FL). Females were estimated to reach median maturity at 329 mm FL (2.4 years) and have a median length at female-to-male sex change of 401 mm FL. Life-history trait values derived here were used to update previous models relating life history and vulnerability to overexploitation. We found that enhancement of just one species' trait values improved model fits considerably, which strengthens the conclusion that life-history traits are a strong determinant of species' vulnerability in the parrotfishes. This information is an imperative complement to other data sources facilitating formal stock assessment of a key fishery target.

Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer.

The majority of pancreatic cancer (PC) patients are clinically presented with obstructive jaundice with elevated levels of circulatory bilirubin and alkaline phosphatases. In the current study, we examined the implications of bile acids (BA), an important component of bile, on the pathophysiology of PC and investigated their mechanistic association in tumor-promoting functions. Integration of results from PC patient samples and autochthonous mouse models showed an elevated levels of BA (p < 0.05) in serum samples compared to healthy controls. Similarly, an elevated BA levels was observed in pancreatic juice derived from PC patients (p < 0.05) than non-pancreatic non-healthy (NPNH) controls, further establishing the clinical association of BA with the pathogenesis of PC. The tumor-promoting functions of BA were established by observed transcriptional upregulation of oncogenic MUC4 expression. Luciferase reporter assay revealed distal MUC4 promoter as the primary responsive site to BA. In silico analysis recognized two c-Jun binding sites at MUC4 distal promoter, which was biochemically established using ChIP assay. Interestingly, BA treatment led to an increased transcription and activation of c-Jun in a FAK-dependent manner. Additionally, BA receptor, namely FXR, which is also upregulated at transcriptional level in PC patient samples, was demonstrated as an upstream molecule in BA-mediated FAK activation, plausibly by regulating Src activation. Altogether, these results demonstrate that elevated levels of BA increase the tumorigenic potential of PC cells by inducing FXR/FAK/c-Jun axis to upregulate MUC4 expression, which is overexpressed in pancreatic tumors and is known to be associated with progression and metastasis of PC.

Pathobiological implications of MUC16 expression in pancreatic cancer.

MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

The use of SPECT-CT in determining 90Y microspheres distribution post selective internal radiation therapy

Hepatocellular carcinoma and metastatic colorectal carcinoma are amongst the more common causes of cancer-related mortality worldwide. Selective internal radiation therapy (SIRT) with 90y microspheres is usually indicated in patients with nonresectable status and extensive colorectal liver metastases that are refractory to chemotherapy or target therapy. Several examinations, including CT, MRI or PET, serum chemical analyses, hepatic angiography and liver-lung shunting study with Tc-99m MAA, are done to ensure appropriateness and safety of therapy. Herein, three cases (two with hepatocellular carcinoma and one with metastatic colorectal cancer), which qualified for SIRT and underwent SPECT-CT, are presented. All of them underwent the necessary pre-therapy work-ups. The CT and PET-CT scans identified the hepatic lesions. The blood tests showed nearly normal hepatic and renal functions, except for the third case with elevated bilirubin level. The hepatic angiograms revealed no significant gastrointestinal shunting. The liver-lung shunting studies computed 10% hepatopulmonary shunt. Together with the patient with an elevated bilirubin level, they received a reduced dose of 90Y microspheres by 20%. After SIRT, bremsstrahlung planar imaging and SPECT-CT were performed to localize the distribution of the 90y microspheres, the findings of which correlated well with the results of the pre-therapy scans. The use of SPECT-CT is recommended for better anatomic localization and functional correlation.

I131 MIBG imaging in the diagnosis of pheochromocytoma: Philippine setting

The clinical diagnosis of pheochromocytoma is easy, considering that it manifests as labile hypertension, attacks of palpitations, headache, sweating, pallor or flushing. Urinary VMA or metanephrines seem to be the first investigative step as well as a CT scan to localize it as 85-90 percent arise from the adrenal medulla. Ten percent of these tumors are bilateral but non-adrenal tumors may arise from the sympathetic ganglia, usually alongside the aorta or its branches and in the wall of the urinary bladder. One percent is found outside the abdominal cavity. Meta-iodobenzyl guanidine (MIBG) is an excellent scanning agent that is taken up by most benign and malignant pheochromocytoma tissues. While this procedure is quite costly and underutilized in the Philippines, this paper was done to review its indications and how helpful it can be. From 2001 -2005, I131 MIBG scintigraphy was done only in 17 patients in two medical centers to confirm the diagnosis of pheochromocytoma. The clinicians must be informed that this is not a screening procedure but it is particularly helpful in surveying the entire body for adrenal and extra-adrenal metastatic lesions. It is also diagnostic of intra-adrenal paragangliomas, neuroblastoma, carcinoids, and medullary thyroid carcinoma. This study was, likewise, done with the thought that MIBG may be utilized in the future for therapy as it has shown to be effective in pheochromocytoma and neuroblastoma.

Precipitación máxima probable en el Estado de Veracruz

En este trabajo se trazaron las isoyetas de precipitación máxima en 24 hors, registrada en todo el Estado de Veracruz. Para esto se recurrió pluviométicos de 67 estaciones que tenían información entre 11 y 30 años. A las precipitaciones máximas se registradas en cada estación se les ajusto la función de distribución de probabilidad de eventos eextremos o de Gumbel, con el objeto de conocer las regiones del Estado. Los valores obtenidos para cada estación pluviométrica se asentaron en un mapa del estado de Veracruz para trazar las isoyetas de precipitación máxima probable en 24 horas, las cuales deben ser tomadas en cuenta para el diseño de estructuras hidráulicas (AU)