Biomedical subjects

Alexander Schneider

Publications and source records attributed to Alexander Schneider.

35 records · Page 2Linked to original sources

PubMed2004

Effect of untreated hypertension on hemorrhagic stroke.

BACKGROUND AND PURPOSE: Stroke is the third leading cause of death and the leading cause of disability in the United States. Intracerebral hemorrhage and subarachnoid hemorrhage represent approximately 20% of all stroke cases and have a mortality rate of 40% to 50%. Hypertension is an important risk factor for these subtypes of stroke. We sought to determine whether untreated hypertension carries a different risk from treated hypertension for hemorrhagic stroke. METHODS: Cases of hemorrhagic stroke in the greater Cincinnati region were identified by screening all area hospital emergency rooms, radiology reports, and International Classification of Diseases 9 codes. Medical records were reviewed for risk factors and medication use. Cases of hemorrhagic stroke were approached for enrollment into the genetic sampling and interview arm. If subjects agreed, the case was matched by age, race, and gender to population-based controls. RESULTS: Between May 1997 and December 2002, we recruited 549 cases of hemorrhagic stroke, of which 322 were intracerebral hemorrhage and 227 were subarachnoid hemorrhage. Untreated hypertension was found to be a significant risk factor for hemorrhagic stroke (odds ratio [OR]=3.5 [2.3 to 5.2]; P<0.0001) as was treated hypertension (OR=1.4 [1.0 to 1.9]; P=0.03). Insurance status of "self-pay" or Medicaid was a significant risk factor for untreated hypertension (OR=2.7 [1.6 to 4.4]). We estimate that 17% to 28% of hemorrhagic strokes among hypertensive patients would have been prevented if they had been on hypertension treatment. CONCLUSIONS: Untreated hypertension is highly prevalent and an important risk factor for hemorrhagic stroke. We estimate that among hypertensive subjects, approximately one fourth of hemorrhagic strokes would be prevented if all hypertensive subjects received treatment.

Female↗

PubMed2004

Hypercholesterolemia, HMG-CoA reductase inhibitors, and risk of intracerebral hemorrhage: a case-control study.

BACKGROUND AND PURPOSE: Several studies have demonstrated an association between hypocholesterolemia and intracerebral hemorrhage (ICH). We tested the hypothesis that hypercholesterolemia or use of HMG-CoA reductase inhibitors (statin) agents, or both, are associated with ICH. METHODS: This study was part of the preplanned midway analysis of an ongoing, population-based, case-control study of the genetic and environmental risk factors of hemorrhagic stroke. Conditional stepwise logistic regression modeling was used to determine if self-reported hypercholesterolemia or statin use, or both, were independent risk factors for ICH. RESULTS: Between December 1, 1997, and June 30, 2000, 188 cases of ICH and 366 age-, race-, and gender-matched controls were enrolled. Hypercholesterolemia and statin use were less common among cases than controls: 25% versus 38% (P=0.003) and 9% versus 17% (P=0.03), respectively. Hypercholesterolemia with statin use was associated with less risk of ICH (OR=0.30; P=0.0008) in multivariable analysis after controlling for alcohol use, hypertension, previous stroke, first-degree relative with ICH, education level, and apolipoprotein E alleles. CONCLUSIONS: Hypercholesterolemia was associated with a lower risk of ICH. We have not found an increased risk of ICH with the widespread use of statins in our population. Given the lack of cholesterol levels in the current study, further studies are needed to determine if lower cholesterol levels secondary to statin use bear the same risk as low cholesterol levels for ICH.

Aged↗

PubMed2004

Genetic analysis of the glutathione s-transferase genes MGST1, GSTM3, GSTT1, and GSTM1 in patients with hereditary pancreatitis.

BACKGROUND: Specific mutations in the cationic trypsinogen gene ( PRSS1) are disease-causing in patients with hereditary pancreatitis, but the genetic background still remains mysterious in about 40% of patients with the disease. It has been suggested that oxidative stress contributes to pancreatic damage. The glutathione s-transferases (GSTs) represent major detoxification enzymes that protect cells from oxidative stress. METHODS: In the present study we tested whether mutations in the MGST1 and GSTM3 genes or common deletions in the GSTT1 and GSTM1 genes are associated with hereditary pancreatitis. We analyzed the entire coding region of MGST1 and GSTM3 in 30 patients that were tested negative for PRSS1 mutations, and we studied 55 controls. For GSTT1 and GSTM1, we investigated 75 hereditary pancreatitis patients who had been tested negative for PRSS1 mutations, 135 hereditary pancreatitis patients with a PRSS1 mutation, and 183 controls. Patients were further subclassified with regard to age of onset of disease as a marker of severity. RESULTS: No mutation was found in the MGST1 gene. In the GSTM3 gene, we detected a homozygous 670G > A polymorphism (V224I) with similar frequencies in patients and controls. We found no difference in the frequencies of the GSTT1 and GSTM1 null genotypes between patients and controls, and we detected no differences in age of onset in patients with or without GSTT1 and GSTM1 deletions. CONCLUSIONS: We conclude that genetic alterations in the MGST1, GSTM3, GSTT1, and GSTM1 genes do not play a dominant role in hereditary pancreatitis.

Adolescent↗

PubMed2004

Analysis of tumor necrosis factor-alpha, transforming growth factor-beta 1, interleukin-10, and interferon-gamma polymorphisms in patients with alcoholic chronic pancreatitis.

The pathophysiologic mechanisms underlying alcoholic chronic pancreatitis are poorly understood. Cytokines participate in the immunologic progression of acute and chronic pancreatitis and may play an important role in the development of pancreatic fibrosis. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at positions -308 and -238; in the transforming growth factor-beta 1 (TGF-beta(1)) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1082; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with alcoholic chronic pancreatitis. We investigated 42 patients with alcoholic chronic pancreatitis. We studied 94 control subjects for the TNF-alpha polymorphisms and 73 control subjects for the remaining polymorphisms. Mutation analysis was performed by direct DNA sequencing or by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The genotype frequencies were similar between patients and control subjects for all investigated cytokine polymorphisms (P>.05). We did not find an association between the different genotypes and the clinical course of the disease. Therefore, we assume that these genetic variants do not play a dominant role in alcoholic chronic pancreatitis.

Alcoholism↗

PubMed2004

Serine protease inhibitor Kazal type 1 mutations and pancreatitis.

In summary, SPINK1 is thought to play an important role in protecting the pancreas against excessive trypsinogen activation. SPINK1 mutations are associated with the development of acute and chronic pancreatitis and have been detected in all forms of chronic pancreatitis. The strong association of mutations in the PRSS1 gene and in the SPINK1 gene with chronic pancreatitis supports the concept of intracellular trypsin activation as an initiating and extremely important step in the development of pancreatitis. The N34S mutation represents the most frequently observed pancreatitis-associated SPINK1 variant. Because the SPINK1 N34S mutation is very common in the general population, it is unlikely that this mutation alone can initiate the development of chronic pancreatitis. Thus, it rather appears that in most patients with SPINK1-associated chronic pancreatitis, this genetic variant acts as disease modifier or within a polygenic model with other yet unidentified genes or environmental cofactors. The possible interaction of mutations in the SPINK1 gene with other pancreatitis-associated susceptibility genes has to be investigated in future research efforts. The most promising candidate gene for such an interaction is the CFTR gene, because genetic alterations within the CFTR gene are also common in the general population and already have been associated with chronic pancreatitis.

Chronic Disease↗

PubMed2004

Stroke in a biracial population: the excess burden of stroke among blacks.

BACKGROUND AND PURPOSE: Excess mortality resulting from stroke is an important reason why blacks have higher age-adjusted mortality rates than whites. This observation has 2 possible explanations: Strokes occur more commonly among blacks or blacks have higher mortality rates after stroke. Our population-based epidemiological study is set in the Greater Cincinnati/Northern Kentucky region of 1.31 million people, which is representative of the US white and black populations with regard to many demographic and socioeconomic characteristics. METHODS: Hospitalized cases were ascertained by International Classification of Diseases (ninth revision) discharge codes, prospective screening of emergency department admission logs, and review of coroner's cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses, followed by physician review. Race-specific incidence and case fatality rates were calculated. RESULTS: We identified 3136 strokes during the study period (January 1, 1993, to June 30, 1994). Stroke incidence rates were higher for blacks at every age, with the greatest risk (2- to 5-fold) seen in young and middle-aged blacks (<65 years of age). Case fatality rates did not differ significantly in blacks compared with whites. Applying the resulting age- and race-specific rates to the US population in 2002, we estimate that 705,000 to 740,000 strokes have occurred in the United States, with a minimum of 616,000 cerebral infarctions, 67,000 intracerebral hemorrhages, and 22,000 subarachnoid hemorrhages. CONCLUSIONS: Excess stroke-related mortality in blacks is due to higher stroke incidence rates, particularly in the young and middle-aged. This excess burden of stroke incidence among blacks represents one of the most serious public health problems facing the United States.

Adult↗

PubMed2003

Animal models in gastrointestinal alcohol research-a short appraisal of the different models and their results.

Alcohol-related diseases of the gastrointestinal tract play an important role in clinical gastroenterology. However, the mechanisms and pathophysiology underlying the effects of ethanol on the organs of the digestive tract are not yet completely understood. Animal models represent an essential tool for investigating alcohol-related diseases because they give researchers the opportunity to use methods that cannot be used in humans, such as knockout technology. However, there is still a need for new animal models resembling the human condition, since for some alcohol-related diseases such as chronic alcoholic pancreatitis, the ideal animal model does not yet exist. In this chapter, we provide an overview of the most commonly used animal models in gastrointestinal alcohol research. We will also briefly discuss the current concepts of the pathophysiological mechanisms involved in acute and chronic alcoholic damage of the oesophagus, stomach, small and large intestine, pancreas and liver.

Alcohol Drinking↗

PubMed2003

Genetic polymorphisms in alcoholic pancreatitis.

Chronic, excessive alcohol consumption is clearly associated with acute and chronic pancreatitis. However, both clinical and laboratory studies have demonstrated that alcohol consumption alone does not directly cause pancreatitis. Growing evidence suggests that environmental and possibly genetic cofactors must also be present before the mechanisms protecting the pancreas from pancreatitis are circumvented and pancreatitis develops. The discovery that mutations in the cationic trypsinogen gene (R122H, N29I) predisposed to acute and chronic pancreatitis focused attention on possible genetic predispositions. Mutations in the cationic trypsinogen gene, however, are rarely associated with alcoholic chronic pancreatitis. Mutations in the SPINK1 gene (e.g. N34S) provide a threefold increased risk, and cystic fibrosis transmembrane conductance regulator (CFTR) mutations continue to be investigated. However, the major cofactor associated with alcoholic chronic pancreatitis is yet to be identified.

Acute Disease↗

PubMed2003

Limited contribution of the SPINK1 N34S mutation to the risk and severity of alcoholic chronic pancreatitis: a report from the United States.

Mutations in the SPINK1 gene (e.g. N34S) have been reported in patients with idiopathic, familial, tropical, and alcoholic pancreatitis. The prevalence of SPINK1 N34S differs between different patient populations, and its contribution to the risk and the severity of alcoholic chronic pancreatitis has not been defined in the United States. Mutational analysis of the exon 3 was performed in 32 patients with alcoholic chronic pancreatitis, 39 patients with nonalcoholic chronic pancreatitis or recurrent acute pancreatitis, and 190 previously studied healthy controls. The course of alcoholic chronic pancreatitis with and without N34S was compared in age of onset- and sex-matched patients. All SPINK1 gene sequence variations were heterozygous. SPINK1 N34S was present in 3/190 (1.6%) and P55S was found in 2/190 (1.1%) of controls. In alcoholics, the N34S mutation was identified in 2/32 patients (6.3%, P > 0.05). In nonalcoholics, N34S and P55S were identified in 6/39 patients (15.4%, P < 0.005, N34S N = 4, P55S N = 1, N34S/P55S N = 1). The clinical course of alcoholic chronic pancreatitis was similar between patients with and without the N34S mutation. The N34S mutation is uncommon in patients with alcoholic chronic pancreatitis in the United States; its prevalence is similar to other countries and appears not to alter the onset or the severity of alcoholic chronic pancreatitis.

Adult↗

PubMed2002

Hereditary pancreatitis: a model for inflammatory diseases of the pancreas.

Acute and chronic pancreatitis remain among the most recalcitrant of all diseases to investigation and intervention. In the majority of patients, excessive alcohol consumption is associated with development of the disease. Therefore, several theories have been proposed seeking to explain the relationship between alcohol and the development of acute and chronic pancreatitis. However, recent investigations in hereditary pancreatitis provided important insights into chronic pancreatitis pathogenesis and offer an important model for understanding pancreatic inflammation. This article highlights several advances gained from investigating hereditary pancreatitis kindreds, and reviews the TIGAR-O risk/aetiology classification system. Finally, the major independent theories on development of chronic pancreatitis are reviewed with respect to the SAPE hypothesis of chronic pancreatitis pathogenesis.

Acute Disease↗

PubMed2002

SPINK1/PSTI mutations are associated with tropical pancreatitis and type II diabetes mellitus in Bangladesh.

BACKGROUND & AIMS: Tropical pancreatitis, including tropical calcific pancreatitis and fibrocalculous pancreatic diabetes, is endemic in parts of Asia and Africa. In a preliminary study, we found serine protease inhibitor, Kazal type 1 (SPINK1) mutations in 6 of 8 patients with fibrocalculous pancreatic diabetes in Bangladesh. A more extensive investigation of patients with pancreatic diseases in Bangladesh, including non-insulin-dependent diabetes mellitus, was undertaken. METHODS: Patients with fibrocalculous pancreatic diabetes (n = 22), tropical calcific pancreatitis (n = 15), and non-insulin-dependent diabetes mellitus (n = 43) and controls (n = 76) from Bangladesh were studied. DNA was extracted, and the SPINK1 gene was sequenced in all patients and 50 controls. Exon 3 was sequenced in an additional 26 controls. RESULTS: SPINK1 N34S mutations appeared in 1 of 76 controls (1.3%), 12 of 22 patients with fibrocalculous pancreatic diabetes (55%; odds ratio, 83; P < 0.00001), 3 of 15 with tropical calcific pancreatitis (20%; odds ratio, 11.2; P = 0.04), and 6 of 43 with non-insulin-dependent diabetes mellitus (14%; odds ratio, 11.9; P = 0.009). P55S was present in 2 of 76 controls (3%) and in 1 of 22 patients with fibrocalculous pancreatic diabetes (5%; P = not significant). A novel Y54H (160T>C) mutation was identified in 1 of 15 tropical calcific pancreatitis patients. CONCLUSIONS: In Bangladesh, the SPINK1 N34S mutation increases the risk of several forms of pancreatic disease, including fibrocalculous pancreatic diabetes, tropical calcific pancreatitis, and non-insulin-dependent diabetes mellitus.

Adult↗

PubMed2002

Genetics and pancreatic disease.

The recognition that variations in the DNA sequence of key genes predispose individuals to acute pancreatitis, chronic pancreatitis, and pancreatic cancer represents one of the greatest breakthroughs in pancreas research. This review highlights recent progress in understanding mutations in the cationic trypsinogen gene, the pancreatic secretory trypsin inhibitor gene, and the cystic fibrosis transmembrane conductance regulator gene with respect to pancreatitis. It also notes progress in the use of microarray technology, classification of chronic pancreatitis, and predisposition to pancreatic cancer.

Journal Article↗

PubMed2002

Two cases of pancreatic tuberculosis in nonimmunocompromised patients. A diagnostic challenge and a rare cause of portal hypertension.

Pancreatic tuberculosis is very rare, especially in immunocompetent patients, and represents a diagnostic challenge. We describe 2 cases of pancreatic tuberculosis mimicking carcinoma on CT scan. In the first case, explorative laparotomy revealed granulomatous inflammation suggestive of tuberculosis. Cultured smears from the pancreatic tail tested positive for Mycobacterium tuberculosis, and the patient responded well to antituberculous medication. In the second case, fine needle aspirate revealed tuberculosis. This case is unique with regard to development of portal hypertension in pancreatic tuberculosis. Antituberculous medication achieved little improvement, then the patient was lost to follow-up. In suspicion of carcinoma the patient underwent laparotomy in another hospital. Malignancy was excluded, and a purulent necrotic pancreas was resected. The patient finally improved without any antituberculous medication and remains well. Both patients were tested HIV-negative. We summarize the etiology, clinical presentation, diagnosis and treatment of a diagnostic dilemma, which should be considered in clinical practice.

Adult↗

PubMed2002

Animal models in alcoholic pancreatitis--what can we learn?

Although the majority of patients with chronic pancreatitis present a history of excessive alcohol consumption, the pathophysiology underlying chronic alcoholic pancreatitis remains poorly defined. Since experimental animal models represent helpful tools in understanding human disease, numerous laboratory studies have been designed to study the effects of alcohol on the pancreas. In the present article we summarize the existing animal models that have been used to investigate the effects of acute and chronic alcohol application on the development of morphological alterations and pancreatic injury. Despite considerable experimental effort, acute or chronic ethanol feeding alone failed to cause acute or chronic pancreatitis in animals. However, ethanol-feeding and the combination with other procedures has demonstrated several mechanisms that play a role in ethanol-induced pancreatic injury. Among these ethanol-induced alterations and mechanisms are the reduction of pancreatic blood-flow and microcirculation, damaging effects of ethanol metabolites, increased pancreatic acinar cell expression of digestive and lysosomal enzymes, increased glandular enzyme content, additional nutritional factors, pancreatic duct obstruction, and limitations of pancreatic regeneration. Although no satisfactory animal model for alcoholic pancreatitis has been developed, these animal models have provided insights in several factors that predispose the pancreas to development of pancreatic injury and contribute to alcoholic pancreatitis.

Alcohol Drinking↗

PubMedDate not supplied

Perimesencephalic subarachnoid hemorrhage: incidence, risk factors, and outcome.

BACKGROUND: Nonaneurysmal perimesencephalic subarachnoid hemorrhage (PMSAH) appears to have an etiology and natural history distinct from aneurysm rupture. Referral-based studies suggest that 15% of SAH patients have no discernable cause of bleeding, but the incidence of PMSAH is unknown. We describe the first population-based study of PMSAH and place it in the context of all non-traumatic SAH, with presentation of incidence rates, patient demographics, and clinical outcomes. METHODS: All patients age >/= 18 hospitalized with first-ever, non-traumatic SAH in the Greater Cincinnati area were identified from 5/98-7/01 and 8/02-4/04. PMSAH was defined as hemorrhage restricted to the cisterns surrounding the brainstem and suprasellar cistern and a negative cerebral angiogram. Incidence rates were age, race, and sex adjusted to the 2000 US population. RESULTS: There were 431 SAHs identified. Cases in Asian-Americans (2) were excluded, leaving 429 SAHs for analysis. Of these patients, 77 did not have angiograms. Among remaining cases, 285 had aneurysm rupture, 43 had nonaneurysmal hemorrhage not of the PMSAH pattern, and 24 had PMSAH. The overall annual incidence rates for SAH and PMSAH were 8.7 (95% CI 7.9-9.5) and 0.5 (95% CI 0.3-0.7) per 100,000 persons age >/= 18. Patients with PMSAH were younger (p = 0.018) and less likely to be female (p = 0.020) or hypertensive (p = 0.005) than other SAH patients. There was one death among PMSAH patients during 14 months mean follow-up. CONCLUSIONS: PMSAH represents approximately 5% of all SAH. Its risk factors and outcome differ from other forms of SAH.

Journal Article↗

PubMedDate not supplied

Genetic epidemiology of intracerebral hemorrhage.

We have previously reported that family history of intracerebral hemorrhage (ICH) was associated with both lobar and nonlobar ICH. We sought to further examine this finding by analyzing differences by age and by apolipoprotein E (Apo E) genotype. All cases of hemorrhagic stroke in the greater Cincinnati area were identified through retrospective screening, and a subset was invited to undergo a direct interview and genetic testing. Interviewed subjects were matched to 2 controls by age, race, and sex. Conditional stepwise logistic regression modeling was used to determine whether having a first-degree relative with an ICH (FHICH) was an independent risk factor for ICH. Between May 1997 and December 2002, we recruited 333 cases of ICH. FHICH was found to be an independent risk factor for both lobar ICH (odds ratio [OR] = 3.9; P = .04) and nonlobar ICH (OR ratio = 5.4; P = .01) after controlling for the presence of numerous variables. Among nonlobar ICH cases, the risk appeared to be predominately in those age < 70 years. The presence of Apo E4 was associated with lobar ICH at age >/= 70 years but not at age < 70 years. Family history of ICH appears to be a significant risk factor for nonlobar ICH at age < 70 years. The presence of Apo E4 appears to be a risk factor for lobar ICH at age >/= 70 years but not at age < 70 years. Family history of ICH is a risk factor for lobar ICH after controlling for the presence of Apo E4.

Journal Article↗

PubMedDate not supplied

Hereditary, familial, and idiopathic chronic pancreatitis are not associated with polymorphisms in the tumor necrosis factor alpha (TNF-alpha) promoter region or the TNF receptor 1 (TNFR1) gene.

PURPOSE: Genetic alterations that are associated with acute and chronic pancreatitis remain to be identified. METHODS: The authors investigated two functionally active tumor necrosis factor (TNF) promoter region polymorphisms at positions -238 and -308 and the entire coding region of the corresponding TNF receptor 1 (TNFR1) gene in 54 patients with hereditary, familial, and idiopathic chronic pancreatitis who were previously tested negative for cationic trypsinogen mutations by direct DNA sequencing. RESULTS: In three patients, we detected novel DNA variants in the TNFR1 gene that did not segregate with the disease. The genotype frequencies of the TNF promoter polymorphisms were similar between patients and controls. CONCLUSION: These polymorphisms are not associated with hereditary, familial, or idiopathic chronic pancreatitis.

Antigens, CD↗