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Performance and role of the breast lesion excision system (BLES) in small clusters of suspicious microcalcifications. - European journal of radiology
To assess the diagnostic performance of the BLES as a biopsy tool in patients with â‰¤1cm clusters of BIRADS 4 microcalcifications, in order to possibly avoid surgical excision in selected patients.This is a retrospective study of 105 patients undergone to stereotactic breast biopsy with the BLES. It excises a single specimen containing the whole mammographic target, allowing better histological assessment due to preserved architecture.Our case series consists of 41 carcinomas (39%) and 64 benign lesions (61%). Cancer involved the specimen margins in 20/41 cases (48.8%) or was close to them (â‰¤1mm) in 14 cases (34.1%); margins were disease-free in only 7 DCIS (17.1%). At subsequent excision of 39/41 malignant cases, underestimation occurred for 5/32 DCIS (15.6%), residual disease was found in 15/39 cancers (38.5%) and no cancer in 19/39 cases (48.7%). For DCIS cases, no residual disease occurred for 66.7% G1-G2 cases and for 35.3% G3 cases (P=0.1556) as well as in 83.3%, 40.0% and 43.8% cases respectively for negative, close and positive BLES margins (P=0.2576).The BLES is a good option for removal of small clusters of breast microcalcifications, giving better histological interpretation, lower underestimation rates and possibly reducing the need of subsequent surgical excision in selected patients.Copyright Â© 2015 Elsevier Ireland Ltd. All rights reserved.
Natural History of Non-Small-Cell Lung Cancer with Bone Metastases. - Scientific reports
We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.
Morphological differences in adipose tissue and changes in BDNF/Trkb expression in brain and gut of a diet induced obese zebrafish model. - Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft
Obesity is a multifactorial disease generated by an alteration in balance between energy intake and expenditure, also dependent on genetic and non-genetic factors. Moreover, various nuclei of the hypothalamus receive and process peripheral stimuli from the gastrointestinal tract, controlling food intake and therefore energy balance. Among anorexigenic molecules, brain-derived neurotrophic factor (BDNF) acts through the tyrosine-kinase receptor TrkB. Numerous data demonstrate that the BDNF/TrkB system has a fundamental role in the control of food intake and body weight. Quantitative PCR and immunohistochemistry for both BDNF and TrkB were used to determine changes in levels in the brain and gastro-intestinal tract of an experimental zebrafish model of diet-induced obesity. Overfed animals showed increased weight and body mass index as well as accumulation of adipose tissue in the visceral, subcutaneous and hepatic areas. These changes were concomitant with decreased levels of BDNF mRNA in the gastro-intestinal tract and increased expression of TrkB mRNA in the brain. Overfeeding did not change the density of cells displaying immunoreactivity for BDNF or TrkB in the brain although both were significantly diminished in the gastro-intestinal tract. These results suggest an involvement of the BDNF/TrkB system in the regulation of food intake and energy balance in zebrafish, as in mammals.Copyright Â© 2015 Elsevier GmbH. All rights reserved.
Preparing the Field for Feasibility Testing of a Parenting Intervention for War-Affected Mothers in Northern Uganda. - Family process
In this article, we discuss the successful implementation of an adapted evidence-based parenting intervention for families affected by two decades of war in Northern Uganda. The adaptation and adoption of such interventions to support mental health and family functioning is widely endorsed by prevention scientists and considered a priority in global mental health. The preparation and early adoption phases of engaging with a highly vulnerable community affected by war trauma are documented in this paper along with a discussion of the steps taken to adapt a parenting intervention for cultural and contextual fit. This study is a component of an overall program of research aimed at reducing the long-term negative effects of war on parenting practices and childhood outcomes, which have considerable implications for preventing mental, neurological, and substance-use disorders. The processes described here cover a 4-year period culminating in the implementation of the nine-session Enhancing Family Connection intervention piloted with a group of 14 mothers. The lessons in cultural adaptation have been valuable and the feasibility results promising for further testing the intervention.Â© 2015 Family Process Institute.
Clinical relevance of corrosion patterns attributed to inflammatory cell-induced corrosion: A retrieval study. - Journal of biomedical materials research. Part B, Applied biomaterials
In vitro studies have shown that human osteoclasts can corrode stainless steel and titanium leading to the production of metal ions responsible for inflammatory reactions. Moreover, traces of cellular activities on metal orthopaedic explants have recently been reported as inflammatory cell-induced (ICI) corrosion being the result of the cells sealing on the metal surfaces and releasing reactive oxygen species (ROS) through Fenton-like reactions. The extent and clinical relevance of this phenomenon has yet to be understood. We analysed a cohort of 100 CoCr alloy hips collected at our retrieval centre; we performed macroscopic and microscopic screening and used statistical analysis to correlate our findings with implant and clinical variables. We found that 59% of our implants had evidence of surface damage consistent with what has previously been described as cell-induced corrosion. There was a significant association between the patterns and aseptic loosening for the ASR modular (râ€‰=â€‰-0.488, pâ€‰=â€‰0.016) and the Durom modular (râ€‰=â€‰0.454, pâ€‰=â€‰0.026). This is the largest implant retrieval study to examine the phenomena of so-called ICI corrosion and is the first to investigate its clinical relevance. We recommend further work to determine the role of cells in the damage patterns observed. Â© 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.Â© 2015 Wiley Periodicals, Inc.
Research Article Flavocoxid Protects Against Cadmium-Induced Disruption of the Blood-Testis Barrier and Improves Testicular Damage and Germ Cell Impairment in Mice. - Toxicological sciences : an official journal of the Society of Toxicology
Cadmium (Cd) causes male infertility. There is the need to identify safe treatments counteracting this toxicity. Flavocoxid is a flavonoid that induces a balanced inhibition of cyclooxygenase (COX)-1 and COX-2 peroxidase moieties and of 5-lipoxygenase (LOX) and has efficacy in the male genitourinary system. We investigated flavocoxid effects on Cd-induced testicular toxicity in mice. Swiss mice were divided into 4 groups: 2 control groups received 0.9% NaCl (vehicle; 1â€‰ml/kg/day) or flavocoxid (20â€‰mg/kg/day ip); 2 groups were challenged with cadmium chloride (CdCl2; 2â€‰mg/kg/day ip) and administered with vehicle or flavocoxid. The treatment lasted for 1 or 2 weeks. The testes were processed for biochemical and morphological studies. CdCl2 increased phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2, tumor necrosis factor (TNF)-Î±, COX-2, 5-LOX, malondialdehyde (MDA), B-cell-lymphoma (Bcl)-2-associated X protein (Bax), follicle-stimulating hormone (FSH), luteinizing hormone (LH), transforming growth factor (TGF) -Î²3, decreased Bcl-2, testosterone, inhibin-B, occludin, N-Cadherin, induced structural damages in the testis and disrupted the blood-testis barrier. Many TUNEL-positive germ cells and changes in claudin-11, occludin, and N-cadherin localization were present. Flavocoxid administration reduced, in a time-dependent way, p-ERK 1/2, TNF-Î±, COX-2, 5-LOX, MDA, Bax, FSH, LH, TGF-Î²3, augmented Bcl-2, testosterone, inhibin B, occludin, N-Cadherin, and improved the structural organization of the testis and the blood-testis barrier. Few TUNEL-positive germ cells were present and a morphological retrieval of the intercellular junctions was observed. In conclusion, flavocoxid has a protective anti-inflammatory, antioxidant, and antiapoptotic function against Cd-induced toxicity in mice testis. We suggest that flavocoxid may play a relevant positive role against environmental levels of Cd, otherwise deleterious to gametogenesis and tubular integrity.Â© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
E5 nucleotide polymorphisms suggest quasispecies occurrence in BPV-1 sub-clinically infected horses. - Research in veterinary science
BPV-1 is known as the main causative agent of equine sarcoid, but the virus has also been detected in skin and blood of healthy horses. Previous reports demonstrated the presence of E5 variants in sarcoids of donkeys and horses; we investigated whether this genetic variability might be also found in BPV-1, PBMC associated, of sub-clinically infected horses. With this aim, we analyzed the E5 gene of 21 BPV-1 strains from diseased and sub-clinically infected horses. Our analyses lead us to demonstrate that multiple sequence variants can be present in the blood of sub-clinically infected horses, with alternative bases corresponding to either synonymous or non-synonymous codons in the E5 oncogene sequences. The results give support to the proposed existence of "equine adapted" BPV-1 strains with the occurrence of viral variants, resembling quasispecies, in clinically healthy horses with viremia.Copyright Â© 2015 Elsevier Ltd. All rights reserved.
Adenomyosis and its impact on women fertility. - Iranian journal of reproductive medicine
Adenomyosis is a widespread disease affecting the reproductive period of women's life. In the last ten years, different pathogenetic hypotheses have been proposed to explain the initiation and development of the disease. This article aims to present and discuss the most important pathophysiologic mechanisms underlying adenomyosis development in order to clarify the relationship between adenomyosis and infertility. A PubMed search was undertaken for English language literature using the MeSH terms 'adenomyosis', 'infertility', 'treatment', and 'pathogenesis'. Although the exact etiology of adenomyosis is unknown, many theories have been proposed. We analysed the most important pathogenic theories expressed and evaluated the potential consequences on women fertility. A better comprehension of the adenomyosis pathogenesis has allowed realizing that adenomyosis may affect young women and may have a great impact on their fertility through different mechanisms. The understanding of these mechanisms helps to clarify the potential usefulness of current therapies.
Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene. - Brain : a journal of neurology
We aimed to characterize genotype-phenotype correlations and establish baseline clinical data for peripheral neuropathies caused by mutations in the myelin protein zero (MPZ) gene. MPZ mutations are the second leading cause of Charcot-Marie-Tooth disease type 1. Recent research makes clinical trials for patients with MPZ mutations a realistic possibility. However, the clinical severity varies with different mutations and natural history data on progression is sparse. We present cross-sectional data to begin to define the phenotypic spectrum and clinical baseline of patients with these mutations. A cohort of patients with MPZ gene mutations was identified in 13 centres of the Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC) between 2009 and 2012 and at Wayne State University between 1996 and 2009. Patient phenotypes were quantified by the Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and the Charcot-Marie-Tooth disease paediatric scale outcome instruments. Genetic testing was performed in all patients and/or in first- or second-degree relatives to document mutation in MPZ gene indicating diagnosis of Charcot-Marie-Tooth disease type 1B. There were 103 patients from 71 families with 47 different MPZ mutations with a mean age of 40 years (range 3-84 years). Patients and mutations were separated into infantile, childhood and adult-onset groups. The infantile onset group had higher Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and slower nerve conductions than the other groups, and severity increased with age. Twenty-three patients had no family history of Charcot-Marie-Tooth disease. Sixty-one patients wore foot/ankle orthoses, 19 required walking assistance or support, and 10 required wheelchairs. There was hearing loss in 21 and scoliosis in 17. Forty-two patients did not begin walking until after 15 months of age. Half of the infantile onset patients then required ambulation aids or wheelchairs for ambulation. Our results demonstrate that virtually all MPZ mutations are associated with specific phenotypes. Early onset (infantile and childhood) phenotypes likely represent developmentally impaired myelination, whereas the adult-onset phenotype reflects axonal degeneration without antecedent demyelination. Data from this cohort of patients will provide the baseline data necessary for clinical trials of patients with Charcot-Marie-Tooth disease caused by MPZ gene mutations.Â© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: email@example.com.
Analysis of connexin expression during seizures induced by 4-aminopyridine in the rat hippocampus. - Journal of biomedical science
In epilepsy, seizures are generated by abnormal synchronous activity in neurons. In the rat hippocampus (HIP), epileptiform activity has been found to be associated with gap junctions (GJs). GJs are formed by the combination of two hemichannels, each composed of six connexins. At low doses, the convulsive drug 4-aminopyridine (4-AP) produces epileptiform activity without affecting glutamate levels; therefore, GJs could participate in its effect. Based on this argument, in this study, the expression of Cx 32, Cx 36 and Cx 43 protein and mRNA in the HIP of rats treated with 4-AP was evaluated. The evaluation of connexins was carried out by chemifluorescent immunoassay, semiquantitative RT-PCR and immunofluorescence to detect the amount and distribution of connexins and of cellular markers in the HIP and dentate gyrus (DG) of animals treated with NaCl and 4-AP in the right entorhinal cortex. In these animals, convulsive behavior and EEG signals were analyzed.The animals treated with 4-AP showed convulsive behavior and epileptiform activity 60Â min after the administration. A significant increase in the protein expression of Cx 32, Cx 36 and Cx 43 was found in the HIP contralateral and ipsilateral to the site of 4-AP administration. A trend toward an increase in the mRNA of Cx 32 and Cx 43 was also found. An increase in the cellular density of Cx 32 and Cx 43 was found in the right HIP and DG, and an increase in the cellular density of oligodendrocytes in the DG and a decrease in the number of cells marked with NeuN were observed in the left HIP.Cx 32 and Cx 43 associated with oligodendrocytes and astrocytes had an important role in the first stages of seizures induced by 4-AP, whereas Cx36 localized to neurons could be associated with later stages. Additionally, these results contribute to our understanding of the role of connexins in acute seizures and allow us to direct our efforts to other new anticonvulsant strategies for seizure treatment.
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