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1.
Transplant Proc ; 48(1): 123-7, 2016.
Article in English | MEDLINE | ID: mdl-26915856

ABSTRACT

INTRODUCTION: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections account for most hepatocellular carcinoma (HCC) and subsequent liver transplant cases. Racial/ethnic disparities exist in access to liver transplantation and post-transplantation survival, and we sought to compare and explore potential disparities in HBV and HCV-related liver transplant populations. METHOD: The Nationwide Inpatient Sample database was used (2001 to 2010). RESULTS: In this study, 2269 liver transplant recipients were included: 56% HCV, 6% HBV, and 37% non-HV. HBV and HCV patients were mostly Asian/Pacific Islander (API) and white, respectively. Within HBV transplant recipients, the mean age was youngest in black patients (P = .02); variation of mean age was not seen within HCV patients. Regarding the transplant recipients' income and insurance, most API and white patients were in the highest income quartile, whereas most black and Hispanic patients were in the lowest income group (P < .001). The most common form of payer across all racial/ethnic groupings was private insurance (P < .001). The mean length of hospitalization was longest in Hispanic patients (P = .008); they had a significantly longer stay compared with white patients (P = .02). The liver transplantations were mostly performed in teaching hospitals, located in urban areas in the West region of the United States (P < .001). CONCLUSION: Differences were found in the HBV and HCV-associated liver transplant populations. More work needs to be done to elucidate disparities regarding black and Hispanic liver transplant recipients as they receive transplants at younger mean ages, are in lower income quartiles, and have longer lengths of hospitalization compared with other racial/ethnic groupings.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Inpatients , Liver Neoplasms/surgery , Liver Transplantation , Transplant Recipients , Adolescent , Adult , Aged , Carcinoma, Hepatocellular/mortality , Female , Graft Survival , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Postoperative Complications , Survival Rate/trends , United States/epidemiology , Young Adult
2.
J Mater Chem B ; 3(40): 7899-7902, 2015 Oct 28.
Article in English | MEDLINE | ID: mdl-26660468

ABSTRACT

Current cell sheet-based blood vessels lack biomimetic structure and require excessively long culture times that may compromise smooth muscle cell phenotype. We modified a commercially available product for uniaxial cell sheet conditioning with thermoresponsive copolymers. Thus, culture of detachable conditioned cell sheets is shortened while retaining structural integrity and contractility.

3.
Clin Infect Dis ; 57(11): 1511-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24046309

ABSTRACT

BACKGROUND: It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. METHODS: A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated. CONCLUSIONS: We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT01052961.


Subject(s)
Antiviral Agents/administration & dosage , Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Influenza, Human/drug therapy , Influenza, Human/virology , Oseltamivir/administration & dosage , Aged , Aged, 80 and over , Antiviral Agents/blood , Antiviral Agents/pharmacokinetics , Female , Hong Kong/epidemiology , Hospitalization , Humans , Influenza, Human/epidemiology , Male , Middle Aged , Nasopharynx/virology , Oseltamivir/blood , Oseltamivir/pharmacokinetics , Prospective Studies , Treatment Outcome , Viral Load
4.
Trop Biomed ; 29(1): 187-90, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22543620

ABSTRACT

This study was conducted to investigate the low prevalence of Dirofilaria immitis in dogs in Johor Bahru as reported by veterinary practitioners, using wet blood mount, Knott's Concentration Test and two heartworm antigen test kits (IDEXX Canine SNAP® 4Dx and RapiGEN®). This study also compared the two test kits used and determined the microfilaria species. Blood were collected from 100 owned dogs and 50 stray dogs in Johor Bahru via cephalic venipuncture. A thick blood smear was done and examined for samples that were positive for microfilaria species identification. The overall prevalence of D. immitis in dogs in Johor Bahru was 1.33% (2/150) and the microfilaria identified was D. immitis. The prevalence of heartworm in owned and stray dogs in this study was 1% and 2% respectively. With only one false negative result from RapiGEN® test kit, comparing the sensitivity between the two test kits could not be achieved. The low prevalence of D. immitis found in this study confirmed anecdotal evidence that prevalence of dirofilariasis is indeed low in Johor Bahru. Additionally, we speculate that dirofilariasis in dogs might be considered as an indicator of vector availability.


Subject(s)
Dirofilaria immitis/isolation & purification , Dirofilariasis/epidemiology , Dirofilariasis/parasitology , Dog Diseases/epidemiology , Dog Diseases/parasitology , Parasitology/methods , Animals , Blood/parasitology , Dogs , Malaysia/epidemiology , Prevalence , Reagent Kits, Diagnostic , Sensitivity and Specificity , Veterinary Medicine/methods
5.
J Musculoskelet Neuronal Interact ; 12(1): 24-7, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22373948

ABSTRACT

The objective of this paper is to provide guidelines for pediatricians, adult physicians in different medical disciplines and patients' families who are planning the transition to adult care for the adolescent with osteogenesis imperfecta (OI). This observational report reflects concerns expressed by patients, their families, and involved physicians regarding the problems encountered with the transition of care. Methods for dealing with transitional issues are presented. OI is a heritable disorder of connective tissue in which fractures are the dominant clinical feature. However, OI is a systemic disorder with broad clinical variability in which there are unpredictable episodes of trauma. Coordinated team support provides the best level of care for the child with OI. This paper discusses 4 key topics related to effecting the transition from pediatric to adult care: 1) Transitioning and maintaining health, 2) Preserving or improving the level of function, 3) Assuring continuity of medical/surgical care, and 4) Re-structuring psychosocial and work-related systems. The process of transition requires active communication between the pediatric and adult team members along with a proactive approach by the patient and family. In addition, as the transition is established, the patient with OI should be encouraged to be his/her own advocate and care coordinator.


Subject(s)
Osteogenesis Imperfecta , Transition to Adult Care , Adolescent , Adult , Humans , Practice Guidelines as Topic
6.
Tropical Biomedicine ; : 187-190, 2012.
Article in English | WPRIM (Western Pacific) | ID: wpr-630171

ABSTRACT

Abstract. This study was conducted to investigate the low prevalence of Dirofilaria immitis in dogs in Johor Bahru as reported by veterinary practitioners, using wet blood mount, Knott’s Concentration Test and two heartworm antigen test kits (IDEXX Canine SNAP® 4Dx and RapiGEN®). This study also compared the two test kits used and determined the microfilaria species. Blood were collected from 100 owned dogs and 50 stray dogs in Johor Bahru via cephalic venipuncture. A thick blood smear was done and examined for samples that were positive for microfilaria species identification. The overall prevalence of D. immitis in dogs in Johor Bahru was 1.33% (2/150) and the microfilaria identified was D. immitis. The prevalence of heartworm in owned and stray dogs in this study was 1% and 2% respectively. With only one false negative result from RapiGEN® test kit, comparing the sensitivity between the two test kits could not be achieved. The low prevalence of D. immitis found in this study confirmed anecdotal evidence that prevalence of dirofilariasis is indeed low in Johor Bahru. Additionally, we speculate that dirofilariasis in dogs might be considered as an indicator of vector availability.

8.
Br J Dermatol ; 164(3): 544-52, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21062265

ABSTRACT

BACKGROUND: Multiple miliary osteoma cutis (MMOC) is a rare nodular skin disease characterized by tiny bone nodules which usually form on the facial skin, typically in middle age. The aetiology of this phenomenon is poorly understood. OBJECTIVES: To search for possible bone formation progenitors and to look for a possible association with mutations in the GNAS gene (encoding the G-protein α-stimulatory subunit) and related hormonal parameters in patients with MMOC. We also reviewed the literature and discuss the aetiology and pathogenesis of adult-onset primary osteomas. METHODS: We report four cases of MMOC. Histological samples were analysed for bone morphogenetic protein (BMP)-2, BMP-4 and oestrogen receptor-α known to be involved in bone formation. Endocrinological laboratory investigations and hand X-rays were performed to exclude a systemic disease. The GNAS gene was sequenced from DNA extracted from peripheral blood in all four patients and from a skin sample in one patient to exclude somatic mutations. RESULTS: Histological analyses revealed intramembranous cutaneous bone formation resembling the findings seen in GNAS gene-based osteoma cutis disorders. However, we did not find any germline or somatic GNAS gene mutations in our patients and all laboratory investigations gave normal results. BMP-2 and -4 were expressed normally in MMOC samples, but oestrogen receptor-α was not expressed. Altogether 47 MMOC cases, 41 female and six male, have been published between 1928 and 2009. Of these cases, 55% had a history of pre-existing acne and only 15% had extrafacial osteomas. CONCLUSIONS: MMOC is a rare but distinct disease entity of unknown aetiology. Histologically, the tiny nodular osteomas show intramembranous superficial ossification but the aetiology appears to be different from GNAS-related disorders. The osteomas seem to increase slowly in number after appearing in middle age.


Subject(s)
Osteoma/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Bone Morphogenetic Protein 2/metabolism , Bone Morphogenetic Protein 4/metabolism , Chromogranins , Estrogen Receptor alpha/metabolism , Facial Neoplasms/pathology , Female , GTP-Binding Protein alpha Subunits, Gs/genetics , Humans , Immunohistochemistry , Male , Middle Aged , Osteoma/genetics , Osteoma/metabolism , Sequence Analysis, DNA , Skin Neoplasms/genetics , Skin Neoplasms/metabolism , Young Adult
9.
Singapore Med J ; 47(6): 499-503, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16752018

ABSTRACT

INTRODUCTION: The objective of this study was to assess the prevalence of young females at risk of developing eating disorders (ED) and the associated socio-demographical variables. METHODS: A set of self-administered questionnaires consisting of an Eating Attitude Test (EAT), an Eating Disorder Inventory (EDI) and a socio-demographical questionnaire was administered to 4,461 young females. Based on scores for EAT and/or EDI-drive for thinness (EDI-DT) subscale, subjects were categorised into either "normal" (NM) or "at risk" (AR) of ED. RESULTS: Mean age of the subjects was 16.7 years (range 12-26 years). The ethnic composition was 78.8 percent Chinese, 11.7 percent Malay, 6.6 percent Indian and 3 percent other ethnic groups. Prevalence of AR was 7.4 percent (95 percent confidence interval [CI] 6.7-8.2 percent). Mean EAT and EDI-DT scores for AR were significantly higher than that of NM (EAT: mean difference is 22.1, 95 percent CI 20.7-23.4, p-value is less than 0.0001; EDI-DT: mean difference is 10.9, 95 percent CI 10.5-11.4, p-value is less than 0.0001). Female Malays constituted a significantly larger proportion of AR (20.6 percent) as compared to NM (10.9 percent). AR females are more likely to use Malay as a spoken language at home (prevalence rate ratio 1.70, p-value is 0.001) and to be better educated with completion of General Certificate of Education (GCE) "O" levels. However, the parents of AR females are likely to be less well educated (below GCE "A" levels). CONCLUSION: The prevalence of females at risk of developing ED is 7.4 percent. Malay ethnic group, using Malay language at home and the educational levels of both the subjects and their parents appear to be associated with an increased risk for development of ED.


Subject(s)
Body Image , Feeding and Eating Disorders/epidemiology , Adolescent , Adult , Body Mass Index , Child , Cross-Sectional Studies , Female , Humans , Prevalence , Risk Assessment , Risk Factors , Singapore/epidemiology , Surveys and Questionnaires
10.
Arch Dis Child ; 91(4): 340-1, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16551788

ABSTRACT

Sturge-Weber syndrome (SWS) is a disorder involving central nervous system abnormalities that may increase the risk of hypothalamic-pituitary dysfunction. Records of 19 patients with suspected growth hormone deficiency (GHD), identified from a registry of 1653 patients with SWS, were reviewed; nine patients with GHD were found.


Subject(s)
Growth Disorders/diagnosis , Human Growth Hormone/deficiency , Sturge-Weber Syndrome/physiopathology , Adolescent , Age Determination by Skeleton , Body Height , Child , Child, Preschool , Female , Humans , Male , Retrospective Studies
11.
Osteoporos Int ; 17(5): 731-40, 2006.
Article in English | MEDLINE | ID: mdl-16505982

ABSTRACT

Few longitudinal data are available characterizing bone development in adolescents with cystic fibrosis (CF) although this is a critical time for bone mineralization. Dual energy X-ray absorptiometry (DXA) scans were obtained at 1- to 4-year intervals in 18 prepubertal and pubertal girls (age 7-18 years) with CF to determine calcium (Ca) accretion rates and changes (Delta) in total body bone mineral content (TBBMC) and lumbar spine bone mineral density (LS BMD) Z-scores. Daily Ca acquisition rates were calculated assuming TBBMC was composed of 32.2% Ca. Bone Ca accretion averaged 82 mg/day (2.05 mmol/day) [(range:-38 to +197 mg/day (-0.95 to 4.9 mmol/day)] on approximately 1,200 mg/day (30 mmol/day) Ca intakes. Estimated mean peak Ca accretion was 160 mg/day (4 mmol/day) at age 13 years; losses of bone Ca occurred in late puberty. Gains in insulin-like growth factor 1 (IGF-1) predicted Ca accretion (p<0.06). Body mass index (BMI) Z-score predicted LS BMD and TBBMC Z-score cross-sectionally but did not predict DeltaTBBMC Z-score. Changes in TBBMC Z-score paralleled Ca accretion rates with age. Bone Ca accretion in girls with CF fell below rates in healthy girls during prepuberty and late puberty despite Ca intakes approaching recommendations. IGF-1 and BMI Z-scores may identify children with CF at risk of compromised bone accretion, and more data are required to elucidate roles of lung function and glucocorticoid use in compromised bone health.


Subject(s)
Bone Density/physiology , Calcium/metabolism , Cystic Fibrosis/physiopathology , Absorptiometry, Photon , Adolescent , Adult , Child , Female , Forced Expiratory Volume/physiology , Humans , Longitudinal Studies , Lumbar Vertebrae/diagnostic imaging , Puberty/physiology , Receptor, IGF Type 1/metabolism
12.
J Membr Biol ; 205(3): 139-45, 2005 Jun.
Article in English | MEDLINE | ID: mdl-16362502

ABSTRACT

The anti-cancer drug cisplatin induces apoptosis by damaging DNA. Since a stilbene-derivative blocker of Cl-/HCO3- exchangers and Cl- channels, SITS, is known to induce cisplatin resistance in a manner independent of intracellular pH and extracellular HCO3-, we investigated the relation between cisplatin-induced apoptosis and Cl- channel activity in human adenocarcinoma KB cells. A stilbene derivative, DIDS, reduced cisplatin-induced caspase-3 activation and cell death, which were detected over 18 h after treatment with cisplatin. DIDS was also found to reduce sensitivity of KB cells to 5-day exposure to cisplatin. Whole-cell patch-clamp recordings showed that KB cells functionally express volume-sensitive outwardly rectifying (VSOR) Cl- channels which are activated by osmotic cell swelling and sensitive to DIDS. Pretreatment of the cells with cisplatin for 12 h augmented the magnitude of VSOR Cl- current. Thus, it is concluded that cisplatin-induced cytotoxicity in KB cells is associated with augmented activity of a DIDS-sensitive VSOR Cl- channel and that blockade of this channel is, at least in part, responsible for cisplatin resistance induced by a stilbene derivative.


Subject(s)
Apoptosis/drug effects , Chloride Channels/physiology , Cisplatin/pharmacology , 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology , 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid/pharmacology , Chloride Channels/drug effects , Humans , KB Cells , Phloretin/pharmacology
13.
Singapore Med J ; 46(6): 275-81, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15902355

ABSTRACT

INTRODUCTION: Information regarding the clinical features of patients with anorexia nervosa in Singapore is rare and there have not been any large studies published to date. The aims of this paper were to study the clinical characteristics and features of patients with anorexia nervosa in Singapore, and to compare the clinical features of the early versus the classical later-onset cases. METHODS: 126 cases presenting to the Child Guidance Clinic and the Eating Disorder Clinic at the Institute of Mental Health between 1994 and 2002 were identified and studied retrospectively. All presented with anorexia nervosa or had a past history of it. Subjects were further classified into early-onset (younger than 14 years) or classical later-onset (14 years and older), and a comparison was done between the two groups. RESULTS: The large majority were female students with a mean presenting age of 17.6 years. 65.1 percent were of the restricting subtype. 84.1 percent were Chinese, 7.9 percent were Indians and 4.8 percent were Malays. Mean presenting body mass index (BMI) was 15.56. Depression was the most common co-morbid condition affecting 25.4 percent of the sample. The number of new cases increased significantly from six in 1994 to 24 in 2002 (p-value equals 0.002). Commonest precipitating factors were comments from others, school and work stress. 11.1 percent were previously members of trim and fit club in school. 42.7 percent of late-onset cases compared to 16.2 percent of the early-onset were of the binge-purge type (p-value equals to 0.005) and had a higher presenting BMI (15.91 +/- 2.90 versus 14.74 +/- 2.14, p-value equals 0.003). CONCLUSION: The clinical characteristics of patients with anorexia nervosa in Singapore are similar to that reported in western literature. The Malay population appears to be under-represented. There was a significant increase in numbers presenting over the last two years. The early-onset cases tend to be of the restrictive-type and had a lower presenting BMI than the later-onset group.


Subject(s)
Anorexia Nervosa/epidemiology , Adolescent , Anorexia Nervosa/psychology , Body Mass Index , Comorbidity , Depression/epidemiology , Female , Humans , Male , Retrospective Studies , Singapore/epidemiology
14.
Hum Exp Toxicol ; 22(8): 445-51, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12948085

ABSTRACT

In Malaysia, the phase 3 registration for traditional medicines was implemented on 1 January 1992 under the Control of Drugs and Cosmetics Regulation 1984, emphasizing quality, efficacy and safety (including the detection of the presence of heavy metals) in all pharmaceutical dosage forms of traditional medicine preparations. Therefore, a total of 100 products in various pharmaceutical dosage forms of a herbal preparation, were analysed for lead content using atomic absorption spectrophotometer. Results showed that 8% (eight products) possessed 10.64-20.72 ppm of lead, and therefore, do not comply with the quality requirement for traditional medicines in Malaysia. One of these products, M-Tongkat Ali (exhibited 10.64 +/-0.37 ppm of lead), was in fact already registered with the DCA Malaysia. The rest, Sukarno Tongkat Ali, Eurycoma Madu, Super Pill Tongkat Ali, Force Pill Tongkat Ali, Tender Pill Tongkat Ali, Super Pill Tongkat Ali Plus and Great Pill Tongkat Ali Plus have not registered with the DCA Malaysia and exhibited 12.24-20.72 ppm of lead. Although this study showed that only 92% of the products complied with the quality requirement for traditional medicines in Malaysia, however, they cannot be assumed safe from lead contamination because of batch-to-batch inconsistency.


Subject(s)
Lead/analysis , Plant Preparations/analysis , Plants, Medicinal/chemistry , Capsules , Drug Combinations , Lead Poisoning/epidemiology , Lead Poisoning/etiology , Malaysia/epidemiology , Plant Preparations/poisoning , Spectrophotometry, Atomic , Tablets
15.
Cancer ; 92(6 Suppl): 1708-13, 2001 Sep 15.
Article in English | MEDLINE | ID: mdl-11598891

ABSTRACT

Cancer-related fatigue is now the most prevalent symptom of cancer, occurring in 60-90% of patients. Fatigue has been identified by cancer patients as a factor influencing functionality and quality of life. Our objectives in developing a fatigue specialty clinic at The University of Texas M. D. Anderson Cancer Center were to improve our patients' quality of life by decreasing fatigue; educate health care providers, patients, and patients' families about cancer-related fatigue; develop an appropriate clinical and diagnostic evaluation for this symptom; correlate objective measures of fatigue with its clinical evaluation; and develop innovative treatment plans for cancer-related fatigue. This article describes the general clinic design and operations and the preliminary analysis of the first 40 patients evaluated in the fatigue clinic.


Subject(s)
Fatigue/therapy , Neoplasms/complications , Outpatient Clinics, Hospital , Adult , Aged , Fatigue/diagnosis , Fatigue/etiology , Female , Humans , Male , Middle Aged , Outpatient Clinics, Hospital/organization & administration
16.
Arch Pathol Lab Med ; 125(10): 1365-7, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11570918

ABSTRACT

Oncocytic schneiderian papillomas (OSPs) are uncommon benign neoplasms that arise from the sinonasal schneiderian epithelium. Malignancies arising in OSPs are rare, and, to our knowledge, only 14 such instances have been reported in the medical literature. We report 2 additional cases--a small cell carcinoma and a sinonasal undifferentiated carcinoma arising in OSPs and presenting synchronously with the benign neoplasm. The potential for malignant transformation in OSPs is small, but warrants that these papillomas be completely excised to exclude a coexisting carcinoma.


Subject(s)
Nasal Mucosa/pathology , Nose Neoplasms/pathology , Papilloma/pathology , Paranasal Sinuses/pathology , Aged , Biomarkers , Biopsy , Carcinoma/pathology , Humans , Immunohistochemistry , Keratins/analysis , Male , Middle Aged , Nose Neoplasms/surgery , Papilloma/surgery
17.
Am J Surg Pathol ; 25(8): 1067-73, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11474292

ABSTRACT

Colchicine is an alkaloid with antimitotic ability used to treat a variety of medical conditions. Colchicine toxicity can result in multiorgan failure and death. The histopathologic features of colchicine toxicity in gastrointestinal biopsies have not been reported. Twenty-one gastrointestinal mucosal biopsies obtained from nine patients receiving oral colchicine therapy were studied. Immunohistochemical staining for Ki67 proliferation antigen was performed, and medical records of each patient were reviewed. All patients had a history of gout. Four patients with chronic renal failure also had clinical evidence of colchicine toxicity, and the other five patients did not. Distinct morphologic changes, seen as metaphase mitoses, epithelial pseudostratification, and loss of polarity, were seen in biopsy material from 4 of 4 (100%) patients with clinical colchicine toxicity. Three of these four cases (75%) also contained abundant crypt apoptotic bodies. These morphologic features were best seen in the biopsies from duodenum and gastric antrum, with relative sparing of the gastric body in the upper gastrointestinal tract. Ki67 staining demonstrated an expansion of the proliferating region in three available cases with clinical colchicine toxicity. These distinctive morphologic features were not seen in the five patients without clinical colchicine toxicity. These results indicate that colchicine toxicity can produce diagnostic morphologic features in gastrointestinal mucosal biopsies. Recognition of these features is important because colchicine toxicity can be fatal if undiagnosed clinically.


Subject(s)
Colchicine/adverse effects , Intestinal Diseases/chemically induced , Intestinal Mucosa/drug effects , Adult , Aged , Aged, 80 and over , Apoptosis , Biopsy , Colon/drug effects , Colon/pathology , Duodenum/drug effects , Duodenum/pathology , Female , Humans , Immunohistochemistry , Intestinal Diseases/metabolism , Intestinal Diseases/pathology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Ki-67 Antigen/metabolism , Male , Middle Aged , Mitosis , Pyloric Antrum/drug effects , Pyloric Antrum/pathology , Rectum/drug effects , Rectum/pathology , Retrospective Studies
18.
Bioorg Med Chem Lett ; 9(18): 2747-52, 1999 Sep 20.
Article in English | MEDLINE | ID: mdl-10509928

ABSTRACT

Analogs of compound 1 with a variety of azacycles and heteroaryl groups were synthesized. These analogs exhibited Ki values ranging from 0.15 to > 10,000 nM when tested in vitro for cholinergic channel receptor binding activity (displacement of [3H](-) cytisine from whole rat brain synaptic membranes).


Subject(s)
Cholinergic Agonists/pharmacology , Animals , Brain/metabolism , Cholinergic Agonists/chemistry , Cholinergic Agonists/metabolism , Ethers/chemistry , Rats , Structure-Activity Relationship
19.
Hum Pathol ; 29(12): 1433-40, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9865829

ABSTRACT

Colonic histopathology in some patients with untreated celiac sprue and refractory sprue has been said to be indistinguishable from lymphocytic colitis, but there have been no objective comparisons on which this is based. The purpose of this study was to determine the prevalence and to characterize the nature of colonic histopathology at the time of diagnosis in patients with celiac or refractory sprue. Colonoscopic biopsy specimens obtained at the time of diagnosis from 16 patients with celiac sprue, six patients with refractory sprue, nine patients with lymphocytic colitis, and five normal controls were analyzed blindly by histological and morphometric methods, quantitating the number and specific subtypes of inflammatory cells within the lamina propria and epithelium. Immunoperoxidase staining of intraepithelial lymphocytes with a monoclonal antibody to CD8 also was performed. Three of 16 patients with untreated celiac sprue (19%) were thought to have colonic histological abnormalities, which by morphometry consisted of slightly increased numbers of lymphocytes in the surface epithelium and lamina propria, many of which were CD8-positive. These abnormalities were distinguishable from lymphocytic colitis by the lack of increased overall lamina propria cellularity and surface epithelial abnormalities, and by fewer intraepithelial lymphocytes. In refractory sprue, colonic histological abnormalities were more frequent than in celiac sprue, occurring in four of six patients (67%), more pronounced, and identical to those in the lymphocytic colitis syndrome. However, colonic intraepithelial lymphocytes in lymphocytic colitis were mostly CD8-positive, whereas those in the colitis of refractory sprue rarely were. Mild colonic lymphocytosis in patients with untreated celiac sprue should be distinguished from lymphocytic colitis by the lack of surface epithelial abnormalities, the lack of increased cellularity of the lamina propria, and the lack of ongoing watery diarrhea after treatment with a gluten-free diet. In contrast, colonic histopathology in refractory sprue is indistinguishable from lymphocytic colitis, although immunohistochemical differences do exist.


Subject(s)
Celiac Disease/diagnosis , Colitis/diagnosis , Colon/pathology , Lymphocytes/pathology , Lymphocytosis/diagnosis , Adolescent , Adult , Aged , Biopsy , CD8 Antigens/metabolism , Celiac Disease/complications , Celiac Disease/metabolism , Chronic Disease , Colitis/complications , Colitis/metabolism , Colon/metabolism , Colonoscopy , Diagnosis, Differential , Diarrhea/etiology , Diarrhea/pathology , Diet, Protein-Restricted , Female , Glutens , Humans , Lymphocytosis/etiology , Lymphocytosis/metabolism , Lymphocytosis/pathology , Male , Middle Aged , Prospective Studies , Single-Blind Method , Treatment Outcome
20.
Am J Surg Pathol ; 22(11): 1404-10, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9808133

ABSTRACT

Gastrointestinal complications of cocaine abuse occur less frequently than those of the cardiovascular and nervous systems. The clinical history and pathologic findings of three patients with cocaine-induced mesenteric ischemia are described, and the mechanism of acute and chronic cocaine-induced mesenteric ischemia is discussed. The role of preoperative angiography in detecting occlusive arterial lesions so that arterial revascularization can be carried out is emphasized. Briefly, recent intravenous cocaine use in a 45-year-old man resulted in sharply demarcated small intestinal ischemia with perforation characterized by pseudomembranous enteritis. Histologic sections of the small-bowel resection showed intraluminal fibrin and intimal hyperplasia in rare submucosal arterioles. Two women, 29 and 35 years of age, both with a 2-year history of intravenous cocaine use, presented with acute abdominal pain and had angiographic documentation of occlusion of the celiac axis and the superior mesenteric arteries. Vascular bypasses were performed in both cases. Microscopic examination of both arteries and their branches revealed total obstruction by luminal thrombus with recanalization.


Subject(s)
Cocaine-Related Disorders/pathology , Cocaine , Intestine, Small/blood supply , Ischemia/pathology , Mesenteric Arteries/pathology , Substance Abuse, Intravenous/complications , Adult , Arterioles/drug effects , Arterioles/pathology , Cocaine-Related Disorders/etiology , Female , Humans , Intestinal Perforation/etiology , Intestinal Perforation/pathology , Intestine, Small/pathology , Ischemia/etiology , Male , Mesenteric Arteries/drug effects , Mesenteric Vascular Occlusion/etiology , Mesenteric Vascular Occlusion/pathology , Middle Aged
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