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Biomedical subjects

J Zimmerman

Publications and source records attributed to J Zimmerman.

At least 19 recordsLinked to original sources

Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas.

Malignant gliomas are frequently characterized by amplification of the epidermal growth factor receptor (EGFR) and loss of PTEN tumor suppressor gene. Twenty-eight heavily pretreated patients with recurrent malignant gliomas were administered EGFR inhibitors (gefitinib or erlotinib) in combination with the mTOR (mammalian target of rapamycin) inhibitor sirolimus. The regimens were reasonably well tolerated. Nineteen percent of patients experienced a partial response and 50% had stable disease. Six-month progression-free survival for glioblastoma patients was 25%.

Adult↗

Selected growth of cubic and hexagonal GaN epitaxial films on polar MgO(111).

Selected molecular beam epitaxy of zinc blende (111) or wurtzite (0001) GaN films on polar MgO(111) is achieved depending on whether N or Ga is deposited first. The cubic stacking is enabled by nitrogen-induced polar surface stabilization, which yields a metallic MgO(111)-(1 x 1)-ON surface. High-resolution transmission electron microscopy and density functional theory studies indicate that the atomically abrupt semiconducting GaN(111)/MgO(111) interface has a Mg-O-N-Ga stacking, where the N atom is bonded to O at a top site. This specific atomic arrangement at the interface allows the cubic stacking to more effectively screen the substrate and film electric dipole moment than the hexagonal stacking, thus stabilizing the zinc blende phase even though the wurtzite phase is the ground state in the bulk.

Journal Article↗

Validation of a brief inventory for diagnosis and monitoring of symptomatic gastro-oesophageal reflux.

BACKGROUND: This article presents a brief inventory for the diagnosis and monitoring of GORD symptoms. METHODS: The inventory consists of five items pertaining to different aspects of GORD to be graded for frequency on a 5-point Likert scale. It was validated on a consecutive group of GORD patients diagnosed either by endoscopy (n = 25) or by 24-h ambulatory pH monitoring (acid exposure time > or = 5%; n = 233) and control subjects (n = 300). RESULTS: Each of the inventory items was significantly associated with GORD (P < 0.001). Factor analysis indicated that all items loaded on a single scale with a high reliability (Cronbach alpha 0.88). Each item was weighted by its respective odds ratio in favour of GORD and a total score for the scale was then calculated as the sum of weighted scores on the five individual items. Receiver-operator (ROC) curve analysis implemented on a random sample comprising 67% of the group indicated that a total weighted score of 31.6 (percentage of the maximal possible weighted score) was 91% sensitive and 92% specific in the diagnosis of GORD. This score was then validated on the rest of the sample, where it correctly classified patients and controls with a sensitivity of 89% and specificity of 94%. The score proved stable on repeated administration in controls and in patients with stable symptoms, and decreased by 66% (P < 0.001) after 1 month of treatment with omeprazole in patients who reported symptom relief. CONCLUSIONS: The scale described in this article is a brief, simple and accurate measure, for the diagnosis of GORD as well as for monitoring its symptoms.

Adult↗

Irritable bowel, smoking and oesophageal acid exposure: an insight into the nature of symptoms of gastro-oesophageal reflux.

BACKGROUND: In gastro-oesophageal reflux disease, oesophageal acid exposure correlates with symptoms but explains only a small fraction of their variance. AIMS: To elucidate the effects of irritable bowel syndrome and smoking on gastro-oesophageal reflux disease symptoms and to clarify whether they modulate the relationship between oesophageal acid exposure and symptoms. METHODS: The relationship between oesophageal acid exposure, irritable bowel syndrome (Rome I criteria), smoking status and symptoms was investigated in patients with a normal gastroscopy who underwent a 24-h oesophageal pH monitoring. RESULTS: Of 256 patients with gastro-oesophageal reflux disease, 16% were smokers and 50% met the criteria for irritable bowel syndrome (irritable bowel syndrome+). The extent of oesophageal acid exposure was unrelated to smoking or irritable bowel syndrome status. Oesophageal acid exposure, irritable bowel syndrome status and current smoking independently predicted symptoms. Irritable bowel syndrome and smoking modulated the effect of oesophageal acid exposure on symptoms: oesophageal acid exposure was predictive of symptoms only in non-smokers. However, irritable bowel syndrome was a significant predictor of symptoms both in smokers and in non-smokers. Smoking was associated with symptoms only in irritable bowel syndrome+, while oesophageal acid exposure was associated with symptoms irrespective of irritable bowel syndrome status. CONCLUSIONS: In patients with non-erosive gastro-oesophageal reflux disease, smoking and irritable bowel syndrome independently predicted symptoms, without affecting the extent of oesophageal acid exposure. The relationship between oesophageal acid exposure and symptoms was affected significantly, and in opposite directions, by smoking and irritable bowel syndrome.

Adult↗

[Severity assessment by APACHE III system in Spain].

BACKGROUND: To assess the performance of the prediction equation of the APACHE(Acute Physiology Age and Chronic Health Evaluation) III prognostic scoring system when applied in Spain. PATIENTS AND METHOD: Prospective multicenter cohort study that included 10786 adult patients from 86 Spanish intensive care units (ICU). Data collection during first 24 hours of admission: acute physiology score, age and comorbilties,for calculating APACHE III score; treatment location prior to ICU admission and main diagnosis admission category for applying the mortality prediction equation of APACHE III system. Main outcome was observed hospital mortality. RESULTS: Age was 57.74 (0.16); 68% males. Non-operative patients represented 76% of sample. APACHE III score was 53.75(0.26); observed and predicted hospital mortality were 21.2% and 19.8% respectively, with a standardized mortality ration of 1.07. The Chi2 Hosmer-Lemershow statistic was (H) 135.6, (C) 133.91: p < 0.001. The area under the Receiver Operating Curve (ROC) was 0.808, and correct classification at mortality risk of 50% was 82%. Uniformity of fit was better for non-operative diagnoses and for patients admitted from the emergency area. Calibration was excellent for risk lower than 60% but slightly underestimated observed risks above this level. CONCLUSIONS: The American APACHE III equation fit well when applied to Spanish critical patients but with limitations. Discrepancies could be attributed to differences in case-mix and variations in practice style.

APACHE↗

A double-blind, multicentered study comparing the accuracy of diagnostic markers to predict short- and long-term clinical events and their utility in patients presenting with chest pain.

BACKGROUND: Millions of patients present annually with chest pain, but only 10% have myocardial infarction (MI). We recently reported comparative sensitivity and specificity of available markers in the diagnosis of MI; however, optimum interpretation of marker results requires prognostic follow-up data. HYPOTHESIS: The study was undertaken to study the accuracy of CK-MB subforms, troponin I and T, myoglobin, and CK-MB in predicting clinical events at 30 days and 6 months. METHODS: In all, 955 consecutive patients with chest pain were enrolled in a prospective, multicenter, double-blind study to test the prognostic accuracy of these markers. RESULTS: Myocardial infarction was diagnosed in 119 by CK-MB mass criteria and unstable angina (UA) in 203 patients by clinical criteria. Follow-up at 30 days and 6 months was available in 824 and 724 patients, respectively, with mortalities of 2.8 and 4.14%, respectively. Cumulative 6-month mortality was 5.6% in MI, 4.4% in UA, and 3.0% in others. Revascularization was reported in 9.3% of patients by 6 months. A positive test on each of the markers except myoglobin was predictive of revascularization. The composite endpoint of death or revascularization occurred in 107 patients by 6 months and a positive result on each of the markers was predictive of this composite endpoint (p < 0.05). The relative risk of death or revascularization for patients who did not have MI but tested positive on each of the markers was > 1.0 but did not reach statistical significance. CONCLUSIONS: With the possible exception of myoglobin, each of the diagnostic markers displayed similar prognostic performance in patients with chest pain presenting to emergency departments. The most appropriate markers to triage patients with chest pain, which has both adequate early diagnostic sensitivity and prognostic accuracy, are the CK-MB subforms.

Adult↗

Dyspepsia as a somatic expression of guilt: a case report.

A 58-year-old woman developed chronic, severe symptoms of heartburn, epigastric pain, and regurgitation that persisted for 2 years. She underwent a thorough evaluation and no organic cause was identified. Therefore, a diagnosis of dyspepsia was made. Her symptoms were refractory to pharmacological treatment. Upon further probing, the patient reported that the onset of her symptoms coincided with the death of her son of cancer 2 years earlier. She blamed herself for the death of her son and admitted to a need for self-punishment. A brief course of treatment using metaphors and hypnosis resulted in a complete resolution of her symptoms, which did not recur during a follow-up of 12 years. This is the first published report of the treatment of dyspepsia using hypnotic methods.

Dyspepsia↗

Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group.

OBJECTIVE: Insulin glargine (HOE 901, 21(A)-Gly-30(B)a-L-Arg-30(B)b-L-Arg human insulin) is a novel recombinant analog of human insulin with a shift in the isoelectric point producing a retarded absorption rate and an increased duration of action that closely mimics normal basal insulin secretion. It recently received approval from the Food and Drug Administration. The aim of this study was to evaluate 2 formulations of insulin glargine for safety and efficacy in the treatment of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a 4-week trial, 256 patients with type 1 diabetes received either NPH insulin or insulin glargine containing 30 microg/ml zinc (insulin glargine[30]) or 80 microg/ml zinc (insulin glargine[80]). Insulin glargine was given subcutaneously once daily at bedtime. NPH insulin was given either once daily (at bedtime) or twice daily (before breakfast and at bedtime), according to the patient's prestudy regimen. The initial doses of insulin glargine and NPH were based on the previous NPH total daily dose. RESULTS: At study end point, insulin glargine-pooled groups had significantly lower fasting plasma glucose (FPG) levels than the NPH insulin group, with adjusted mean FPG levels reduced by 2.2 mmol/l (P = 0.0001). Insulin glargine was superior to NPH insulin in reducing FPG levels in patients who had previously received NPH insulin twice daily but not in patients who had previously received NPH once daily. FPG levels were more stable in patients using insulin glargine than in patients using NPH insulin. A subset of patients (n = 71) underwent hourly overnight plasma glucose measurements. Insulin glargine patients exhibited lower FPG levels after 5:00 A.M.; the difference was significant by 8:00 A.M. The adjusted mean FPG for insulin glargine[30] was 7.8 mmol/l; for insulin glargine[80], 7.3 mmol/l; and for NPH, 10.7 mmol/l. Both formulations of insulin glargine were well tolerated, similar to NPH insulin. CONCLUSIONS: Basal insulin glargine administered once daily for 4 weeks as part of a basal-bolus multiple daily insulin regimen was safe and more effective in lowering fasting plasma glucose levels than NPH in patients with type 1 diabetes.

Adult↗

Diagnostic marker cooperative study for the diagnosis of myocardial infarction.

BACKGROUND: Millions of patients present annually with chest pain, but only 10% to 15% have myocardial infarction. Lack of diagnostic sensitivity and specificity of clinical and conventional markers prevents or delays treatment and leads to unnecessary costly admissions. Comparative data are lacking on the new markers, yet using all of them is inappropriate and expensive. METHODS AND RESULTS: The Diagnostic Marker Cooperative Study was a prospective, multicenter, double-blind study with consecutive enrollment of patients with chest pain presenting to the emergency department. Diagnostic sensitivity and specificity and frequency of increase in patients with unstable angina were determined for creatine kinase-MB (CK-MB) subforms, myoglobin, total CK-MB (activity and mass), and troponin T and I on the basis of frequent serial sampling for </=24 hours. Of 955 patients with chest pain, 119 (12.5%) had infarction identified by use of CK-MB mass, and 203 (21%) had unstable angina. CK-MB subforms were most sensitive and specific (91% and 89%) within 6 hours of onset, followed by myoglobin (78% and 89%). For late diagnosis, total CK-MB activity (derived from subforms) was the most sensitive and specific (96% and 98%) at 10 hours from onset, followed by troponin I (96% and 93%), but not until 18 hours, and troponin T (87% and 93% at 10 hours). In unstable angina, CK-MB subforms were increased in 29.5%, myoglobin in 23.7%, troponin I in 19.7%, and troponin T in 14.8%. All markers were increased in 99 patients. With each marker as the diagnostic standard, CK-MB subforms and myoglobin remained the most sensitive for early diagnosis. CONCLUSIONS: The CK-MB subform assay alone or in combination with a troponin reliably triages patients with chest pain and should lead to improved therapy and reduced cost.

Angina, Unstable↗

PGG-glucan, a soluble beta-(1,3)-glucan, enhances the oxidative burst response, microbicidal activity, and activates an NF-kappa B-like factor in human PMN: evidence for a glycosphingolipid beta-(1,3)-glucan receptor.

PGG-Glucan, a soluble beta-(1,6)-branched beta-(1,3)-linked glucose homopolymer derived from the cell wall of the yeast Saccharomyces cerevisiae, is an immunomodulator which enhances leukocyte anti-infective activity and enhances myeloid and megakaryocyte progenitor proliferation. Incubation of human whole blood with PGG-Glucan significantly enhanced the oxidative burst response of subsequently isolated blood leukocytes to both soluble and particulate activators in a dose-dependent manner, and increased leukocyte microbicidal activity. No evidence for inflammatory cytokine production was obtained under these conditions. Electrophoretic mobility shift assays demonstrated that PGG-Glucan induced the activation of an NF-kappaB-like nuclear transcription factor in purified human neutrophils. The binding of 3H-PGG-Glucan to human leukocyte membranes was specific, concentration-dependent, saturable, and high affinity (Kd approximately 6 nM). A monoclonal antibody specific to the glycosphingolipid lactosylceramide was able to inhibit activation of the NF-kappaB-like factor by PGG-Glucan, and ligand binding data, including polysaccharide specificity, suggested that the PGG-Glucan binding moiety was lactosylceramide. These results indicate that PGG-Glucan enhances neutrophil anti-microbial functions and that interaction between this beta-glucan and human neutrophils is mediated by the glycosphingolipid lactosylceramide present at the cell surface.

Adjuvants, Immunologic↗

Giant fibrovascular polyp of the esophagus.

Giant fibrovascular polyps (FVP) are the most common intraluminal tumors of the esophagus. The case of a second, nonrecurrent FVP is presented. A thorough review of the literature was conducted to provide an informative discussion on this benign but potentially life-threatening neoplasm.

Esophageal Neoplasms↗

Decreased seroprevalence for Toxoplasma gondii in Seventh Day Adventists in Maryland.

Despite its widespread prevalence, uncertainties remain about the relative contribution of various routes of transmission to the overall rate of infection with Toxoplasma gondii, particularly in developed countries. To explore the hypothesis that meat consumption is an important risk factor for infection, a cross-sectional seroprevalence study was performed on healthy adults in one region in the state of Maryland. The population included Seventh Day Adventists who as a group follow a diet containing no meat, and control community volunteers who were not Seventh Day Adventists. Thirty-one percent of the population had serologic evidence of T. gondii infection. People with T. gondii infection were older (49 versus 42 years old; P < 0.01, by t-test) and less likely to be Seventh Day Adventists (24% versus 50%; P < 0.01, by chi-square test) than people without T. gondii infection. When adjustments were made for age and gender through multiple logistic regression, Seventh Day Adventists had a significantly decreased risk of T. gondii infection (odds ratio = 0.21, 95% confidence interval = 0.09-0.46, P = 0.0001) compared with the controls. While the basis for this effect remains to be determined, one possible protective factor is the general adherence of Seventh Day Adventists to a diet that does not contain meat.

Adult↗