B Strom - Academia.edu (original) (raw)
Papers by B Strom
Nature communications, Oct 16, 2017
Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defe... more Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defects in these signaling pathways have been shown to impair T cell activation. The effects of PI3Kγ and PI3Kδ on alloimmunity remain underexplored. Here, we show that both PI3Kγ (-/-) and PI3Kδ (D910A/D910A) mice receiving heart allografts have suppression of alloreactive T effector cells and delayed acute rejection. However, PI3Kδ mutation also dampens regulatory T cells (Treg). After treatment with low dose CTLA4-Ig, PI3Kγ (-/-) , but not PI3Κδ (D910A/D910A) , recipients exhibit indefinite prolongation of heart allograft survival. PI3Kδ (D910A/D910A) Tregs have increased apoptosis and impaired survival. Selective inhibition of PI3Kγ and PI3Kδ (using PI3Kδ and dual PI3Kγδ chemical inhibitors) shows that PI3Kγ inhibition compensates for the negative effect of PI3Kδ inhibition on long-term allograft survival. These data serve as a basis for future PI3K-based immune therapies for transplanta...
The Journal of Experimental Medicine, 1973
The capacity of allosensitized thymus-derived lymphocytes to destroy target cells bearing donor a... more The capacity of allosensitized thymus-derived lymphocytes to destroy target cells bearing donor alloantigens is modulated by the cellular levels of cyclic AMP and cyclic GMP. Increases in the cyclic AMP levels of attacking lymphocytes by stimulation with prostaglandin E1, isoproterenol, and cholera toxin inhibit lymphocyte-mediated cytotoxicity; whereas, depletion of cyclic AMP with imidazole enhances cytotoxicity. The augmentation of cytotoxicity produced by cholinergic stimulation with carbamylcholine is not associated with alterations in cyclic AMP levels and is duplicated by 8-bromo-cyclic GMP. The effects of activators of adenylate cyclase, cholinomimetic agents, and 8-bromocyclic GMP are upon the attacking and not the target cells and occur at the time of initial interaction of attacking and target cells. Indeed, the level of cyclic nucleotide (cyclic AMP and cyclic GMP) at the time of initial cell-to-cell interaction determines the extent of cytotoxicity.
Journal of the International AIDS Society, 2012
Background: Toll-like receptors (TLRs) are transmembrane receptors that activate cells of the inn... more Background: Toll-like receptors (TLRs) are transmembrane receptors that activate cells of the innate immune systems upon recognition of pathogen-associated molecular patterns. The TLR4 is an essential component of the innate immune response to various microorganisms. We investigated the impact of TLR4 polymorphism on development of opportunistic diseases in HIV-infected patients. Methods: The presence of TLR4 Asp299Gly single nucleotide polymorphisms (SNPs) was determined in a cohort of 180 antiretroviral treatment-naive HIV-1 infected patients and evaluated in relation to the occurrence of opportunistic infections. TLR4 genotyping was performed by real-time PCR. Results: One hundred sixty-five patients were homozygous for the wild-type genotype (AA); 15 patients (8,3%) were heterozygous for the Asp299Gly SNP (AG). TLR4 polymorphism was associated with more frequent development of the opportunistic infections, such as active tuberculosis (OR 03.27; 95% CI [1.21Á10.29]), herpes zoster (OR 04.15; 95% CI [1.24Á7.29]) and toxoplasmosis (OR 06.23; 95% CI [1.19Á18.67]) compared with genotype AA. In addition, TLR4 SNP was associated with development of opportunistic diseases among individuals with CD4 cell count of !100 cells/mm 3 , compared with homozygous HIV-infected patients (OR, 5.25; 95%, CI [2.28Á10.47]). Conclusion: This study suggests a greater risk of developing of active tuberculosis and other opportunistic infections in patients with the Asp299Gly TLR4 polymorphism.
to explore the vortex-induced vibration (VIV) behavior of a flat plate mounted on a virtual sprin... more to explore the vortex-induced vibration (VIV) behavior of a flat plate mounted on a virtual spring damper support. The plate is allowed to oscillate about its mid-chord and the measured angular position, velocity, and torque are used as inputs to a feedback control system that provides a restoring torque and can simulate a wide range of structural dynamic behavior. A series of experiments were carried out using different sized plates, and over a range of freestream velocities, equilibrium angles of attack, and simulated stiffness and damping. We observe a synchronization phenomenon over a wide range of parameter space, wherein the plate oscillates at moderate to large amplitude with a frequency dictated by the natural structural frequency of the system. Additionally, the existence of bistable states is reflected in the hysteretic response of the system. The cyber-physical damping extracts energy from the flow and the efficiency of this harvesting mechanism is characterized over a range of dimensionless stiffness and damping parameters.
American Journal of Epidemiology, 2012
Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whe... more Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (P trend < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years. endometrial neoplasms; parity; reproductive history Abbreviations: BMI, body mass index; CI, confidence interval; E2C2, Epidemiology of Endometrial Cancer Consortium; OC, oral contraceptive; OR 5 , odds ratio per 5-year increase.
The Journal of otolaryngology, 1983
With the new high resolution CT scanners with target reconstruction, detailed radiological anatom... more With the new high resolution CT scanners with target reconstruction, detailed radiological anatomy can be assessed. Hence, very small structures within the petrous portion of the temporal bone are accessible owing to better density resolution. Not only bony structures but also soft tissue elements are directly visible, which represents an advantage over multidirectional conventional tomography. This technique is described and examples of the normal anatomy of the temporal bone are presented.
Journal of virology, 1971
Methyl methanesulfate-induced lesions in bacteriophage T4 are repaired primarily by a mechanism i... more Methyl methanesulfate-induced lesions in bacteriophage T4 are repaired primarily by a mechanism involving polynucleotide ligase. Apparently, other recombinational and ultraviolet repair functions aren't involved.
Obstetrics and gynecology, 1987
The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed... more The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed in a hospital-based study of 61 women suffering from a first episode of idiopathic deep vein thrombosis or pulmonary embolism (cases) and 1278 women admitted for trauma or respiratory infections (controls). Twenty (33%) of the cases and 121 (9%) of the controls had used oral contraceptives within the previous month, yielding an age-adjusted relative risk estimate of 8.1 (95% confidence interval 3.7 to 18) for recent users relative to never-users. For women using oral contraceptives containing less than 50 micrograms estrogen, the relative risk estimate was 11 (3.7 to 22); for preparations with 50 micrograms estrogen, it was 5.5 (2.1 to 15); and for preparations with more than 50 micrograms estrogen, it was 11 (3.9 to 30). Past use of oral contraceptives was not associated with an increased risk. The data suggest that the risk of venous thromboembolism is increased for recent oral contra...
Gastroentérologie clinique et biologique, 1988
Vasopressin (VS) has been reported to stimulate colonic peristalsis in different therapeutic cond... more Vasopressin (VS) has been reported to stimulate colonic peristalsis in different therapeutic conditions. In order to determine the mechanisms involved in this effect, colonic function was studied with three different techniques staying: a) the transit time of radioopaque markers through the colon was measured in 7 healthy subjects after VS IM (0.3 U/kg of weight). A marked propulsive effect was observed. One hour after injection, 64.7 +/- 16.2 p. 100 of the markers (m +/- sem) had left the right colon vs 9.1 +/- 4.6 p. 100 after injection of NaCl (p less than 0.01) and 70.5 +/- 10.8 p. 100 of the markers emptied from the left colon vs 4.3 +/- 4.5 p. 100 after NaCl (p less than 0.01); b) an electromyographic study was carried out in 6 other healthy subjects with an intraluminal device equipped with contact electrodes, introduced into the left colon by colonoscopy. The injection of VS was followed by an increase in the number of the propagating electrical spike bursts that are known t...
Gynecologic Oncology, 2012
… Research/Fundamental and …, 1972
In bacteriophage T 4 , temperature-sensitive (ts) mutations in gene 32 as well as in gene 43 have... more In bacteriophage T 4 , temperature-sensitive (ts) mutations in gene 32 as well as in gene 43 have previously been shown to stimulate reversion of frame-shift mutations. We show here that twots mutations in gene 32 increase reversion of base substitution mutations.ts mutations in ...
Clinical Pharmacology …, 2001
The erythromycin breath test (EBT) has been extensively used for more than a decade as a noninvas... more The erythromycin breath test (EBT) has been extensively used for more than a decade as a noninvasive in vivo probe of cytochrome P4503A (CYP3A) activity and as a potential tool for dosing individualization of CYP3A substrate drugs. l-6 The popularity of this test could be illustrated in part by more than 100 literature citations of an early important review article by Watkins.3 The EBT is relatively simple, fast, safe, and highly reproducible in the same individuals with a coefficient of variation of only 4.9% reported recently.' The test has also been extensively validated in humans and
Hepatology, 1996
spectively, P°.0001 for each comparison), even after To evaluate the a priori hypotheses that an ... more spectively, P°.0001 for each comparison), even after To evaluate the a priori hypotheses that an increased excluding those with a serum bilirubin higher than 2.0 level of glyco and tauro lithocholic acid, perhaps bemg/dL. Bile cholesterol was lower for the cases as well cause of a decreased capacity for hepatic sulfation, con-(median 1.70 mmol/mL vs. 4.90 mmol/mL and 16.81 mmol/ tributed to the biochemical epidemiology of gallbladder mL, respectively, P°.02), as was the concentration of cancer, a case-control study was undertaken at four hosbile phospholipids (median 2.97 mmol/mL vs. 6.26 mmol/ pitals in La Paz, Bolivia, and at one hospital in Mexico mL and 52.69 mmol/mL, P Å .1 and .0004, respectively). City, Mexico. Eighty-four cases with newly diagnosed Contrary to our a priori hypothesis, there was no differhistologically confirmed gallbladder cancer were comence between the cases and either control group in their pared with 264 controls with cholelithiasis or choledobile concentrations of lithocholate, the proportion of bile cholithiasis in the absence of cancer and with 126 conacids which were sulfated, or the concentration of nontrols with normal biliary tracts. All study subjects were sulfated lithocholate. However, the cases had a higher undergoing abdominal surgery. Interview data were colconcentration of ursodeoxycholate (UDC) (P õ .004 for lected for all study subjects, as well as blood, bile, and both control groups), especially glycoursodeoxycholate gallstone specimens when feasible. Sera were analyzed (P õ .001 for both control groups). A previously pubfor carcinoembryonic antigen, cholesterol concentralished suggestion that gallstone size differed between tion, and total bile acids. Bile specimens were analyzed cases and controls was not confirmed. In conclusion, for carcinoembryonic antigen; and for concentration of cases with gallbladder cancer differed from controls bile salts; cholesterol; phospholipids; and the glycine with stones and from controls with normal biliary tracts and taurine conjugates of cholic, ursodeoxycholic, chein their serum and bile biochemistries. These findings nodeoxycholic, deoxycholic, and lithocholates; sulfoglymay be a reflection of the disease process, or may procolithocholate; and sulfotaurolithocholate. Gallstone vide useful clues to its pathogenesis. (HEPATOLOGY specimens were analyzed for the percentage of choles-1996;23:1402-1411.) terol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus The study of gallbladder cancer provides a unique the two control groups (median 11.7 nmol/mL vs. 9.3 opportunity to combine biochemistry and epidemiology nmol/mL for stone controls and 8.2 nmol/L for nonstone to investigate the possible cause of cancers that are controls, P°.02 for each pairwise comparison). Biliary uncommon in the United States' black and white popubile acids were markedly decreased in the cases (median 3.98 mmol/mL vs. 33.09 mmol/mL and 154.0 mmol/L, relations , but of considerable international importance among Hispanic, and especially Amerind, populations. 1 Different parts of the biliary tract are bathed in the Abbreviations: HDL, high-density lipoprotein; HPLC, high-pressure liquid same material: bile. Yet, there are important differchromatography; TUDC, taurousodeoxycholate; GUDC, glycoursodeoxychoences in the epidemiology of cancers of the liver, the late; GC, glycocholate; TCDC, taurochenodeoxycholate; GCDC, glycochenointrahepatic bile ducts, the extrahepatic bile ducts, the deoxycholate; CDC, chenodeoxycholate; DC, deoxycholate; UDC, ursodeoxycholate; UDCA, ursodeoxycholic acid. ampulla of Vater, and the gallbladder. 2 In addition, From 1 the Center for Clinical Epidemiology and Biostatistics, Department there are marked differences in the incidence of these of Biostatistics and Epidemiology, and Division of General Internal Medicine diseases across countries. 1,3 These findings have led to of the
Archives of Internal Medicine, 1992
To determine the incidence of agranulocytosis, a descriptive epidemiologic study was performed. W... more To determine the incidence of agranulocytosis, a descriptive epidemiologic study was performed. With the use of computerized Medicaid billing data from 1980 through 1985 from Minnesota, Michigan, and Florida, the ratio of persons hospitalized with a discharge diagnosis of neutropenia to persons with any claim for medical service was first used as an estimate of the incidence rate of the condition. Patients with cancer and patients receiving cytotoxic and immunosuppressive drugs were excluded. The information provided by a review of medical records for a subset of neutropenia cases was used to determine the proportion with neutropenia after excluding cases with recurrent or chronic neutropenia, and to determine the proportion with agranulocytosis. The incidence rates (95% confidence intervals) of agranulocytosis, excluding recurrent or chronic disease, were 2.3 (1.4 to 3.7), 7.7 (6.6 to 8.9), and 15.4 (11.3 to 20.4) per million per year in each state, respectively. The overall incidence was 7.2 (6.3 to 8.1) per million per year. Agranulocytosis is an extremely uncommon condition. The excess risk of agranulocytosis due to any drug other than cytotoxic drugs must, therefore, be very low.
Nature communications, Oct 16, 2017
Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defe... more Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defects in these signaling pathways have been shown to impair T cell activation. The effects of PI3Kγ and PI3Kδ on alloimmunity remain underexplored. Here, we show that both PI3Kγ (-/-) and PI3Kδ (D910A/D910A) mice receiving heart allografts have suppression of alloreactive T effector cells and delayed acute rejection. However, PI3Kδ mutation also dampens regulatory T cells (Treg). After treatment with low dose CTLA4-Ig, PI3Kγ (-/-) , but not PI3Κδ (D910A/D910A) , recipients exhibit indefinite prolongation of heart allograft survival. PI3Kδ (D910A/D910A) Tregs have increased apoptosis and impaired survival. Selective inhibition of PI3Kγ and PI3Kδ (using PI3Kδ and dual PI3Kγδ chemical inhibitors) shows that PI3Kγ inhibition compensates for the negative effect of PI3Kδ inhibition on long-term allograft survival. These data serve as a basis for future PI3K-based immune therapies for transplanta...
The Journal of Experimental Medicine, 1973
The capacity of allosensitized thymus-derived lymphocytes to destroy target cells bearing donor a... more The capacity of allosensitized thymus-derived lymphocytes to destroy target cells bearing donor alloantigens is modulated by the cellular levels of cyclic AMP and cyclic GMP. Increases in the cyclic AMP levels of attacking lymphocytes by stimulation with prostaglandin E1, isoproterenol, and cholera toxin inhibit lymphocyte-mediated cytotoxicity; whereas, depletion of cyclic AMP with imidazole enhances cytotoxicity. The augmentation of cytotoxicity produced by cholinergic stimulation with carbamylcholine is not associated with alterations in cyclic AMP levels and is duplicated by 8-bromo-cyclic GMP. The effects of activators of adenylate cyclase, cholinomimetic agents, and 8-bromocyclic GMP are upon the attacking and not the target cells and occur at the time of initial interaction of attacking and target cells. Indeed, the level of cyclic nucleotide (cyclic AMP and cyclic GMP) at the time of initial cell-to-cell interaction determines the extent of cytotoxicity.
Journal of the International AIDS Society, 2012
Background: Toll-like receptors (TLRs) are transmembrane receptors that activate cells of the inn... more Background: Toll-like receptors (TLRs) are transmembrane receptors that activate cells of the innate immune systems upon recognition of pathogen-associated molecular patterns. The TLR4 is an essential component of the innate immune response to various microorganisms. We investigated the impact of TLR4 polymorphism on development of opportunistic diseases in HIV-infected patients. Methods: The presence of TLR4 Asp299Gly single nucleotide polymorphisms (SNPs) was determined in a cohort of 180 antiretroviral treatment-naive HIV-1 infected patients and evaluated in relation to the occurrence of opportunistic infections. TLR4 genotyping was performed by real-time PCR. Results: One hundred sixty-five patients were homozygous for the wild-type genotype (AA); 15 patients (8,3%) were heterozygous for the Asp299Gly SNP (AG). TLR4 polymorphism was associated with more frequent development of the opportunistic infections, such as active tuberculosis (OR 03.27; 95% CI [1.21Á10.29]), herpes zoster (OR 04.15; 95% CI [1.24Á7.29]) and toxoplasmosis (OR 06.23; 95% CI [1.19Á18.67]) compared with genotype AA. In addition, TLR4 SNP was associated with development of opportunistic diseases among individuals with CD4 cell count of !100 cells/mm 3 , compared with homozygous HIV-infected patients (OR, 5.25; 95%, CI [2.28Á10.47]). Conclusion: This study suggests a greater risk of developing of active tuberculosis and other opportunistic infections in patients with the Asp299Gly TLR4 polymorphism.
to explore the vortex-induced vibration (VIV) behavior of a flat plate mounted on a virtual sprin... more to explore the vortex-induced vibration (VIV) behavior of a flat plate mounted on a virtual spring damper support. The plate is allowed to oscillate about its mid-chord and the measured angular position, velocity, and torque are used as inputs to a feedback control system that provides a restoring torque and can simulate a wide range of structural dynamic behavior. A series of experiments were carried out using different sized plates, and over a range of freestream velocities, equilibrium angles of attack, and simulated stiffness and damping. We observe a synchronization phenomenon over a wide range of parameter space, wherein the plate oscillates at moderate to large amplitude with a frequency dictated by the natural structural frequency of the system. Additionally, the existence of bistable states is reflected in the hysteretic response of the system. The cyber-physical damping extracts energy from the flow and the efficiency of this harvesting mechanism is characterized over a range of dimensionless stiffness and damping parameters.
American Journal of Epidemiology, 2012
Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whe... more Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (P trend < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years. endometrial neoplasms; parity; reproductive history Abbreviations: BMI, body mass index; CI, confidence interval; E2C2, Epidemiology of Endometrial Cancer Consortium; OC, oral contraceptive; OR 5 , odds ratio per 5-year increase.
The Journal of otolaryngology, 1983
With the new high resolution CT scanners with target reconstruction, detailed radiological anatom... more With the new high resolution CT scanners with target reconstruction, detailed radiological anatomy can be assessed. Hence, very small structures within the petrous portion of the temporal bone are accessible owing to better density resolution. Not only bony structures but also soft tissue elements are directly visible, which represents an advantage over multidirectional conventional tomography. This technique is described and examples of the normal anatomy of the temporal bone are presented.
Journal of virology, 1971
Methyl methanesulfate-induced lesions in bacteriophage T4 are repaired primarily by a mechanism i... more Methyl methanesulfate-induced lesions in bacteriophage T4 are repaired primarily by a mechanism involving polynucleotide ligase. Apparently, other recombinational and ultraviolet repair functions aren't involved.
Obstetrics and gynecology, 1987
The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed... more The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed in a hospital-based study of 61 women suffering from a first episode of idiopathic deep vein thrombosis or pulmonary embolism (cases) and 1278 women admitted for trauma or respiratory infections (controls). Twenty (33%) of the cases and 121 (9%) of the controls had used oral contraceptives within the previous month, yielding an age-adjusted relative risk estimate of 8.1 (95% confidence interval 3.7 to 18) for recent users relative to never-users. For women using oral contraceptives containing less than 50 micrograms estrogen, the relative risk estimate was 11 (3.7 to 22); for preparations with 50 micrograms estrogen, it was 5.5 (2.1 to 15); and for preparations with more than 50 micrograms estrogen, it was 11 (3.9 to 30). Past use of oral contraceptives was not associated with an increased risk. The data suggest that the risk of venous thromboembolism is increased for recent oral contra...
Gastroentérologie clinique et biologique, 1988
Vasopressin (VS) has been reported to stimulate colonic peristalsis in different therapeutic cond... more Vasopressin (VS) has been reported to stimulate colonic peristalsis in different therapeutic conditions. In order to determine the mechanisms involved in this effect, colonic function was studied with three different techniques staying: a) the transit time of radioopaque markers through the colon was measured in 7 healthy subjects after VS IM (0.3 U/kg of weight). A marked propulsive effect was observed. One hour after injection, 64.7 +/- 16.2 p. 100 of the markers (m +/- sem) had left the right colon vs 9.1 +/- 4.6 p. 100 after injection of NaCl (p less than 0.01) and 70.5 +/- 10.8 p. 100 of the markers emptied from the left colon vs 4.3 +/- 4.5 p. 100 after NaCl (p less than 0.01); b) an electromyographic study was carried out in 6 other healthy subjects with an intraluminal device equipped with contact electrodes, introduced into the left colon by colonoscopy. The injection of VS was followed by an increase in the number of the propagating electrical spike bursts that are known t...
Gynecologic Oncology, 2012
… Research/Fundamental and …, 1972
In bacteriophage T 4 , temperature-sensitive (ts) mutations in gene 32 as well as in gene 43 have... more In bacteriophage T 4 , temperature-sensitive (ts) mutations in gene 32 as well as in gene 43 have previously been shown to stimulate reversion of frame-shift mutations. We show here that twots mutations in gene 32 increase reversion of base substitution mutations.ts mutations in ...
Clinical Pharmacology …, 2001
The erythromycin breath test (EBT) has been extensively used for more than a decade as a noninvas... more The erythromycin breath test (EBT) has been extensively used for more than a decade as a noninvasive in vivo probe of cytochrome P4503A (CYP3A) activity and as a potential tool for dosing individualization of CYP3A substrate drugs. l-6 The popularity of this test could be illustrated in part by more than 100 literature citations of an early important review article by Watkins.3 The EBT is relatively simple, fast, safe, and highly reproducible in the same individuals with a coefficient of variation of only 4.9% reported recently.' The test has also been extensively validated in humans and
Hepatology, 1996
spectively, P°.0001 for each comparison), even after To evaluate the a priori hypotheses that an ... more spectively, P°.0001 for each comparison), even after To evaluate the a priori hypotheses that an increased excluding those with a serum bilirubin higher than 2.0 level of glyco and tauro lithocholic acid, perhaps bemg/dL. Bile cholesterol was lower for the cases as well cause of a decreased capacity for hepatic sulfation, con-(median 1.70 mmol/mL vs. 4.90 mmol/mL and 16.81 mmol/ tributed to the biochemical epidemiology of gallbladder mL, respectively, P°.02), as was the concentration of cancer, a case-control study was undertaken at four hosbile phospholipids (median 2.97 mmol/mL vs. 6.26 mmol/ pitals in La Paz, Bolivia, and at one hospital in Mexico mL and 52.69 mmol/mL, P Å .1 and .0004, respectively). City, Mexico. Eighty-four cases with newly diagnosed Contrary to our a priori hypothesis, there was no differhistologically confirmed gallbladder cancer were comence between the cases and either control group in their pared with 264 controls with cholelithiasis or choledobile concentrations of lithocholate, the proportion of bile cholithiasis in the absence of cancer and with 126 conacids which were sulfated, or the concentration of nontrols with normal biliary tracts. All study subjects were sulfated lithocholate. However, the cases had a higher undergoing abdominal surgery. Interview data were colconcentration of ursodeoxycholate (UDC) (P õ .004 for lected for all study subjects, as well as blood, bile, and both control groups), especially glycoursodeoxycholate gallstone specimens when feasible. Sera were analyzed (P õ .001 for both control groups). A previously pubfor carcinoembryonic antigen, cholesterol concentralished suggestion that gallstone size differed between tion, and total bile acids. Bile specimens were analyzed cases and controls was not confirmed. In conclusion, for carcinoembryonic antigen; and for concentration of cases with gallbladder cancer differed from controls bile salts; cholesterol; phospholipids; and the glycine with stones and from controls with normal biliary tracts and taurine conjugates of cholic, ursodeoxycholic, chein their serum and bile biochemistries. These findings nodeoxycholic, deoxycholic, and lithocholates; sulfoglymay be a reflection of the disease process, or may procolithocholate; and sulfotaurolithocholate. Gallstone vide useful clues to its pathogenesis. (HEPATOLOGY specimens were analyzed for the percentage of choles-1996;23:1402-1411.) terol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus The study of gallbladder cancer provides a unique the two control groups (median 11.7 nmol/mL vs. 9.3 opportunity to combine biochemistry and epidemiology nmol/mL for stone controls and 8.2 nmol/L for nonstone to investigate the possible cause of cancers that are controls, P°.02 for each pairwise comparison). Biliary uncommon in the United States' black and white popubile acids were markedly decreased in the cases (median 3.98 mmol/mL vs. 33.09 mmol/mL and 154.0 mmol/L, relations , but of considerable international importance among Hispanic, and especially Amerind, populations. 1 Different parts of the biliary tract are bathed in the Abbreviations: HDL, high-density lipoprotein; HPLC, high-pressure liquid same material: bile. Yet, there are important differchromatography; TUDC, taurousodeoxycholate; GUDC, glycoursodeoxychoences in the epidemiology of cancers of the liver, the late; GC, glycocholate; TCDC, taurochenodeoxycholate; GCDC, glycochenointrahepatic bile ducts, the extrahepatic bile ducts, the deoxycholate; CDC, chenodeoxycholate; DC, deoxycholate; UDC, ursodeoxycholate; UDCA, ursodeoxycholic acid. ampulla of Vater, and the gallbladder. 2 In addition, From 1 the Center for Clinical Epidemiology and Biostatistics, Department there are marked differences in the incidence of these of Biostatistics and Epidemiology, and Division of General Internal Medicine diseases across countries. 1,3 These findings have led to of the
Archives of Internal Medicine, 1992
To determine the incidence of agranulocytosis, a descriptive epidemiologic study was performed. W... more To determine the incidence of agranulocytosis, a descriptive epidemiologic study was performed. With the use of computerized Medicaid billing data from 1980 through 1985 from Minnesota, Michigan, and Florida, the ratio of persons hospitalized with a discharge diagnosis of neutropenia to persons with any claim for medical service was first used as an estimate of the incidence rate of the condition. Patients with cancer and patients receiving cytotoxic and immunosuppressive drugs were excluded. The information provided by a review of medical records for a subset of neutropenia cases was used to determine the proportion with neutropenia after excluding cases with recurrent or chronic neutropenia, and to determine the proportion with agranulocytosis. The incidence rates (95% confidence intervals) of agranulocytosis, excluding recurrent or chronic disease, were 2.3 (1.4 to 3.7), 7.7 (6.6 to 8.9), and 15.4 (11.3 to 20.4) per million per year in each state, respectively. The overall incidence was 7.2 (6.3 to 8.1) per million per year. Agranulocytosis is an extremely uncommon condition. The excess risk of agranulocytosis due to any drug other than cytotoxic drugs must, therefore, be very low.