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Biomedical subjects

H Harder

Publications and source records attributed to H Harder.

At least 19 recordsLinked to original sources

[Probiotics as therapeutic agents in irritable bowel syndrome].

Probiotics are defined as living micro-organisms which, when administered in large amounts, confer a health benefit on the host. The use of probiotics in the therapy of infectious bowel diseases as well as maintaining remission of ulcerative colitis and in pouchitis is evidence-based. Also, in several studies proof could be supplied that specific probiotics relieve the symptoms and the course of irritable bowel syndrome. Some trials showed a significant improvement of irritable bowel syndrome-related constipation via Lactobacillus casei Shirota and E. coli Nissle 1917. Lactobacillus plantarum has been proven effective in reducing pain and abdominal bloating. However, in most of the studies rather small numbers of patients were examined. Furthermore, these studies do not always closely follow scientific standards (randomised, double-blind, placebo-controlled). Therefore, confirmatory studies are necessary to examine the effect of probiotics in irritable bowel syndrome.

Follow-Up Studies↗

Cognitive status and quality of life after treatment for primary CNS lymphoma.

OBJECTIVE: To evaluate the cognitive status and quality of life (QOL) in a cohort of 19 consecutive patients treated in a prospective European Organization for Research and Treatment of Cancer study (20962) for primary CNS lymphoma (PCNSL). All patients were in complete remission after combined modality treatment with IV and intrathecal high-dose methotrexate (MTX)-based chemotherapy followed by whole brain radiotherapy (WBRT). METHODS: An extensive neuropsychological assessment, including QOL measures, was conducted in 19 patients with PCNSL. The results were compared with matched control subjects with systemic hematologic malignancies treated with systemic chemotherapy or non-CNS radiotherapy. In addition, a neuroradiologic evaluation was carried out in 18 patients with PCNSL. RESULTS: Cognitive impairment was found in 12 patients with PCNSL (63%) despite a complete tumor response. Four patients (21%) showed severe cognitive deficits, and the percentage of impaired test indices correlated with age. In comparison, only two control subjects (11%) showed cognitive dysfunction (p = 0.002). Forty-two percent of the patients with PCNSL, in contrast to 81% of the control subjects, resumed work. White matter abnormalities were observed in 14 patients with PCNSL, and 14 had cortical atrophy. Cortical atrophy correlated with cognitive functioning, age, and Karnofsky performance score. Group differences in cognitive status and QOL could not be explained by anxiety, depression, or fatigue. CONCLUSIONS: Combined modality treatment for primary CNS lymphoma is associated with cognitive impairment even in patients aged <60 years.

Adult↗

The effect of a rapid weight loss on lipid profile and glycemic control in obese type 2 diabetic patients.

OBJECTIVE: To test the effect of low calorie diet (LCD) on body weight, lipid profile, and glycemic control in obese type 2 diabetes mellitus (DM) patients. DESIGN: Dietary intervention. SETTING: Department of Human Nutrition, Copenhagen. SUBJECTS: Outpatients: 11 type 2 DM patients (three males/eight females) (10 completed), four on oral hypoglycemic agents (OHA). Body mass index (BMI) 36.8 +/- 5.5 kg/m2 and age 62 +/- 5.7 y. INTERVENTIONS: In all, 8 weeks full meal-replacement diet: eight sachets of a nutrition powder (Nutrilett, 850 kcal/day). Lipid profile assessed by NMR spectroscopy. RESULTS: Mean body weight fell by 10.9 kg (approximately 11%, P<0.001). Fasting insulin, fasting blood glucose, hemoglobin A1c, fasting plasma triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol fell significantly. There were large positive changes (statistically insignificant) in LDL subclass distribution and a similar shift in high-density lipoprotein subclass distribution. Medication was discontinued in all four subjects taking OHA for 2 weeks prior to the intervention and throughout the whole 8-week intervention period. CONCLUSION: LCD is effective in improving glycemic control and blood lipids through weight loss in overweight type 2 DM patients.

Blood Glucose↗

Effect of ethanol and some alcoholic beverages on gastric emptying in humans.

BACKGROUND: There is a paucity of detailed and controlled studies on the action of ethanol and alcoholic beverages on gastric emptying in humans. This study was designed to compare the effect of beer, red wine, whisky and their comparable pure ethanol solutions on gastric emptying in a controlled and randomized investigation. METHODS: On separate days, 10 healthy, fasted subjects received the following solutions, in random order, through a gastric tube: 500 mL beer, red wine, comparable pure ethanol solutions (4% and 10% v/v), glucose (5.5% and 11.4% w/v) and water, 125 mL whisky and 40% (v/v) ethanol (both followed by 125 mL water) and 250 mL water. Gastric emptying of the test solutions was assessed using ultrasonography of the antrum. RESULTS: As measured by ultrasonography of the antrum, half emptying times of the ethanol solutions (4%, 10% and 40% v/v) were significantly (P < 0.05) longer (22.6 +/- 4.8, 22.7 +/- 4.3 and 27.8 +/- 3.3 min, respectively, n=10) than those of water (14.6 +/- 1.9 min (500 mL) and 13.2 +/- 1.7 min (250 mL), respectively). The half emptying times of beer (39.3 +/- 4.3 min) and red wine (72.6 +/- 7.6 min) were significantly longer than those of the corresponding ethanol concentrations, whereas whisky was emptied at nearly the same rate (26.4 +/- 5.9 min) as 40% (v/v) ethanol. Emptying of glucose 5.5% and 11.4% (w/v) was significantly and dose dependently slower (29.7 +/- 4.5 and 64.8 +/- 8.9 min) than water. CONCLUSIONS: 1) Pure ethanol in concentrations of 4%, 10% and 40% (v/v) inhibits gastric emptying. 2) The inhibitory effect of beer and red wine, but not of whisky, is stronger than that of their comparable ethanol concentrations. 3) Caloric content and non-alcoholic ingredients in alcoholic beverages produced by fermentation (beer and wine), but not in those produced by distillation (whisky), are most likely responsible for this effect.

Adult↗

Reliability of the [13C]-acetate breath test in the measurement of gastric emptying of ethanol solutions: a methodological study.

BACKGROUND: The [13C]-acetate breath test is a clinically well-established test for measuring gastric emptying of liquids and correlates significantly with scintigraphy. However, no studies have been undertaken to examine the relationship between gastric emptying measured by the [13C]-acetate breath test and ultrasonography. Furthermore, it is not known how ethanol may affect gastric emptying as measured by the [13C]-acetate breath test. This is particularly important because of the additional steps of absorption, metabolism and exhalation of the tracer involved in the [13C]-acetate breath test compared to the simple measurement of gastric emptying by ultrasonography. The aim of the present study was to examine the relationship between the gastric half emptying times measured by the [13C]-acetate breath test and by ultrasonography and to determine the effect of ethanol on the comparability between both methods. METHODS: On separate days, 10 healthy, fasted randomly selected subjects received the following solutions by gastric tube: 500 mL water, 4% and 10% (v/v) ethanol, 5.5% and 11.4 % (w/v) glucose. Gastric half emptying times of the test solutions were simultaneously determined using the [13C]-acetate breath test and ultrasonography of the fundus and the antrum. RESULTS: The gastric emptying rates determined by ultrasonography of the fundus correlated significantly with the results obtained using the [13C]-acetate breath test for all test solutions (r = 0.64-0.92, P < 0.05 for all), whereas ultrasonography of the antrum correlated significantly with the breath test only when water (r = 0.94, P = 0.001) was used. The difference between the mean half-emptying times obtained using the [13C]-acetate breath test and ultrasonography of the fundus was 55 +/- 1.8 min. This difference was significantly longer when 4% and 10% (v/v) ethanol solutions were given (61.2 +/- 3.3 and 71.2 +/- 2.9 min) compared to water (P < 0.05). CONCLUSIONS: A good correlation was found between gastric emptying as measured by the [13C]-acetate breath test and ultrasonography of the fundus. Measurements that were obtained using the [13C]-acetate breath test demonstrate a longer gastric half emptying time compared with those obtained using ultrasonography. This difference is even more marked when ethanol solutions are used. Presumably, this is because ethanol affects the absorption and/or the hepatic metabolism of the tracer. The [13C]-acetate breath test is therefore not a reliable gastric emptying test for comparison of different solutions, especially when ethanol-containing liquids are used.

Acetates↗

Direct measurements of urban OH reactivity during Nashville SOS in summer 1999.

Emissions of volatile chemicals control the hydroxyl radical (OH), the atmosphere's main cleansing agent, and thus the production of secondary pollutants. Accounting for all of these chemicals can be difficult, especially in environments with mixed urban and forest emissions. The first direct measurements of the atmospheric OH reactivity, the inverse of the OH lifetime, were made as part of the Southern Oxidant Study (SOS) at Cornelia Fort Airpark in Nashville, TN in summer 1999. Measured OH reactivity was typically 11 s(-1). Measured OH reactivity was 1.4 times larger than OH reactivity calculated from the sum of the products of measured chemical concentrations and their OH reaction rate coefficients. This difference is statistically significant at the 1sigma uncertainty level of both the measurements and the calculations but not the 2sigma uncertainty level. Measured OH reactivity was 1.3 times larger than the OH reactivity from a model that uses measured ambient concentrations of volatile organic compounds (VOCs), NO, NO2, SO2, and CO. However, it was within approximately 10% of the OH reactivity from a model that includes hydrocarbon measurements made in a Nashville tunnel and scaled to the ambient CO at Cornelia Fort Airpark. These comparisons indicate that 30% of the OH reactivity in Nashville may come from short-lived highly reactive VOCs that are not usually measured in field intensive studies or by US EPA's Photochemical Assessment Monitoring Stations.

Air Pollutants↗

Intestinal gas distribution determines abdominal symptoms.

BACKGROUND: Patients with functional gut disorders manifest poor tolerance to intestinal gas loads but the mechanism of this dysfunction is unknown. AIM: Our aims were firstly, to explore the relative importance of the amount of intestinal gas versus its distribution on symptom production, and secondly, to correlate gut motility and perception of gas loads. SUBJECTS: Fourteen healthy subjects with no gastrointestinal symptoms. METHODS: In each subject a gas mixture was infused (12 ml/min) either into the jejunum or rectum for one hour during blocked rectal gas outflow, and subsequently gas clearance was measured over one hour of free rectal evacuation. We measured abdominal perception, distension, and gut tone by duodenal and rectal barostats. RESULTS: Similar magnitude of gas retention (720 ml) produced significantly more abdominal symptoms with jejunal compared with rectal infusion (perception score 4.4 (0.4) v 1.5 (0.5), respectively; p<0.01) whereas abdominal distension was similar (15 (2) mm and 14 (1) mm girth increment, respectively). Jejunal gas loads were associated with proximal contraction (by 57 (5)%) and colonic loads with distal relaxation (by 99 (20)%). CONCLUSION: The volume of gas within the gut determines abdominal distension whereas symptom perception depends on intraluminal gas distribution and possibly also on the gut motor response to gas loads.

Abdomen↗

High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CGH methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.

Adolescent↗

Tolerability of the cytoprotective agent amifostine in elderly patients receiving chemotherapy: a comparative study.

In order to determine if age and comorbidity influence the tolerability of the cytoprotective agent amifostine, we compared side effects related to amifostine in patients > or = 70 years (group I) with patients < 70 years (group II). We evaluated 268 consecutive administrations of amifostine (119 in group I and 149 in group II, respectively), given i.v. at a dose of 740 mg/m(2) just before platinum-, taxol- or cyclophosphamide-based chemotherapy. Transient hypotension was the most common side effect occurring in association with amifostine. Decreases in systolic blood pressure > 20 mmHg were of similar frequency in both groups (27.1 versus 28.8% of amifostine infusions in group I and II, respectively). Hypotension did not result in medical sequelae in any of the patients. The amifostine infusion was interrupted 16 times in group I and 8 times in group II, respectively, mainly due to hypotension, but could be restarted after a few minutes in all patients except for three cases in group I. Patients in group II more often suffered from nausea/vomiting than in group II (20.8 versus 10.0% in group I). Other subjective symptoms (e.g. warmed, flushed sensation, sneezing, metallic taste, mouth dryness, dizziness and sleepiness) and hypocalcemia occurred with a similar frequency in both groups. Adverse effects associated with amifostine were not observed more frequently in elderly patients than in younger ones, although more elderly patients had a comorbidity than the younger ones.

Adult↗

Speech recognition in background noise: monaural versus binaural listening conditions in normal-hearing patients.

HYPOTHESIS: Patients with unilateral conductive hearing impairment often experience a great advantage in improved hearing thresholds after reconstructive ear surgery because the binaural hearing leads to increased speech recognition in competing noise. The aim of this study was to develop a clinical audiometric test to quantify the ability of speech recognition in background noise preoperatively and postoperatively. METHODS: A model consisting of phonetically balanced (PB) monosyllabic words and/or a just-follow-conversation test (JFC) was used in 16 normal-hearing listeners. In 8 of the participants, JFC at two levels of background noise (60 and 40 dB sound pressure level) was used as the only method. The tasks were performed in an anechoic chamber with varying spatial separations of speech and noise sources under free field conditions. The tests were made binaurally and monaurally; the latter condition was achieved by occluding one ear with a hearing protector. In PB word tests, the percent of correctly repeated words was scored. In the JFC task, the speech signal was adjusted by the listener to a level where he or she could just understand what was being said. This was expressed as a signal-to-noise (S/N) ratio. RESULTS: In both types of tests, the subjects achieved significantly better speech recognition scores in the binaural situations. In summary, compared with monaural conditions, the subjects achieved 17% to 18% better speech recognition in PB tests, and in JFC tests a 2-to 3-dB lower S/N ratio in binaural conditions. CONCLUSION: These free field tests can be developed further as a clinical tool preoperatively and postoperatively to evaluate the effect of binaural hearing after ear surgery.

Audiometry, Pure-Tone↗

Neuropathy under chemotherapy.

Neuropathy is a dose-limiting side effect for a number of effective chemotherapeutic agents. A better understanding of effective mechanisms will lead to novel treatment strategies that will protect neurons without decreasing therapeutic efficacy. The assessment of the efficacy and neurotoxicity of various chemotherapeutic agents is vital, for a determination of the maximum allowable dose. The introduction of chemotherapy in the 50s and 60s of the twentieth century has resulted in the development of curative therapeutic interventions for patients with several types of solid tumours and hemopoietic neoplasms. The important obstacles encountered in the use of chemotherapy have been the toxicity to the normal tissue. During the past 8 years there has come about a new level of understanding of the mechanisms through which chemotherapeutic agents work. This has opened the door to new paradigms of treatment in which molecular, genetic, and biologic therapy can be used together to increase the sensitivity of abnormal cells to treatment, and to protect the normal tissues of the body from therapy-induced side effects. The implementation of new strategies could change the way therapy is delivered over the next few years and improve the outcome especially in patients with neoplasms that are currently resistant to conventional dose therapy.

Antineoplastic Agents↗

Radiofrequency, Centimeter-Wave, Millimeter-Wave, and Infrared Spectra of SiHF(3): Investigation of the Ground, v(4) = 1, and v(6) = 1 Vibrational States.

The present paper deals with the analysis of the microwave, millimeter-wave, and infrared spectra of (28)SiHF(3) in its ground, v(6) = 1 and v(4) = 1 excited states. The former was observed up to 1055 GHz leading to the determination of one octic centrifugal distortion constant, L(J) = -0.0749(55) µHz. Furthermore the interaction term ||h(3,GS) || = 1.1032(70) mHz has been fitted from splittings of six K = 3 lines. The excited states have been regarded as isolated ones. This enabled fits according the Q-, D-, and QD-reduction schemes proposed by E. I. Lobodenko, O. N. Sulakshina, V. I. Perevalov, and Vl. G. Tyuterev, (J. Mol. Spectrosc. 126, 159-170 (1987)) and further developed by J. K. G. Watson, C. Gerke, H. Harder, and K. Sarka, (J. Mol. Spectrosc. 187, 131-141 (1997)) and Harder (J. Mol. Spectrosc. 194, 145 (1999)). A multiple fit analysis was performed confirming the assumption that the excited states are not affected by intervibrational resonances. Finally the millimeter spectrum of (29)SiHF(3) and (30)SiHF(3) in their ground state was also measured up to 460 GHz and accurate rotational and centrifugal distortion parameters were derived. Copyright 2000 Academic Press.

Journal Article↗

Coincidence of Gaucher's disease due to a 1226G/1448C mutation and of an immunoglobulin G lambda multiple myeloma with Bence-Jones proteinuria.

We report about a 58-year-old female with coexisting type-I Gaucher's disease (GD) and multiple myeloma (MM). The diagnosis of GD was made in early childhood by means of bone marrow biopsy and was recently confirmed by analysis of the patient's genomic DNA for the underlying glucocerebrosidase mutations and the identification of the 1226G/1448C genotype. At the age of 24 years, the patient developed massive splenomegaly. Therefore, a splenectomy was performed. No further therapy was necessary for the next 34 years until 1999 when progressive anemia and thrombocytopenia occurred. Additional laboratory analysis revealed high serum protein and immunoglobulin (Ig) G levels and evidence of monoclonal gammopathy and lambda light-chain proteinuria, indicating plasma cell dyscrasia. This diagnosis was confirmed by the detection of osteolytic lesions in skeletal X-rays and a bone marrow biopsy showing an extensive infiltration with Gaucher cells and an increase of plasma cells, which expressed lambda light chains. When examined by means of electron microscopy, typical Gaucher cells, i.e., histiocytes containing tubular-structured cytoplasmatic material and spots of plasma cells with an increase of the endoplasmic reticulum, were found. GD associated with acquired MM has been described 13 times in the literature from 1968 to 1997. Only three of the patients were suffering from IgG myeloma. This distribution of the monoclonal component is in contrast to that of patients suffering from MM alone.

Bence Jones Protein↗

MRI screening of the cerebellopontine angle and inner ear with fast spin-echo T2 technique.

In patients with unilateral hearing loss and dizziness it is important to rule out a cerebellopontine angle process. This is often done by audiological and otoneurological investigations. However, in many cases we must rely on the imaging of the temporal bone and the cerebello-brainstem area. The paper has presented the three dimensional (3D) Fast Spin-Echo (FSE) T2 weighted, 0.7 mm thick MR images, which in addition to being quick, does not require the use of expensive contrast material. Between September 1996 and November 1997, 152 patients with unilateral hearing loss and/or balance disorders were investigated. In normal cases the 7th and 8th nerves could be followed accurately from the brainstem to the internal auditory meatus. The found tumors were hypointense compared to the cerebrospinal fluid and could be outlined with reasonable accuracy even without gadolinium contrast. The inner ear had high signal, like cerebrospinal fluid. The patency of the cochlea could be estimated accurately. Thus, 3D FSE T2 weighted images can reliably differentiate between patients with and without pathologies of the cerebellopontine angle. The use of gadolinium contrast could be avoided in most of the cases, but contrast is necessary for differential diagnostic purposes in patients with alterations in the cerebellopontine angle or in doubtful cases.

Artifacts↗

Radio-Frequency, Centimeter-Wave, Millimeter-Wave, and Infrared Spectra of SiDF(3) in the v(6) = 1 Excited State.

This paper deals with the first study of high-resolution radio-frequency, centimeter-wave, millimeter-wave, and infrared spectra of the deuterated isotopomer of trifluorosilane, SiDF(3), in its lowest degenerate excited v(6) = 1 state. Following the work of E. I. Lobodenko, O. N. Sulakshina, V. I. Perevalov, and Vl. G. Tyuterev, (J. Mol. Spectrosc. 126, 159-170 (1987)) and Harder (J. Mol. Spectrosc. 194, 145 (1999)), the data (18 A(1)-A(2) transitions, 229 l-type resonance transitions, 189 pure rotational transitions, and 1167 rovibrational transitions) have been fitted using three equivalent Q, D, and QD reduction schemes enabling the fit of one of the three interaction parameters d, q(12), and epsilon, respectively, while the other two are fixed to zero. In addition to further higher order constants, either f(K)(22) or tau(K) also had to be constrained. By checking the standard deviation of each data set and the relations between parameters determined within different constrains, the six reduction schemes have been shown to be unitary equivalent. Furthermore, the axial rotational ground state constant C(0) has been accurately determined. Copyright 1999 Academic Press.

Journal Article↗

The Reduced Effective Vibration-Rotational Hamiltonian for the v(t) = 2 Levels of C(3v) Symmetric-Top Molecules.

The theory of the reduction of the effective rotation-vibration Hamiltonian is applied to the v(t) = 2 states of C(3v) molecules, and the higher-order terms up to H(43) are included. The results explain clearly why it is possible to determine in this state all four spectroscopic constants eta(J), eta(K), q(12), and d(t) simultaneously without the indeterminacy problems that have been encountered in the v(t) = 1 states. Constraints suitable for most cases are proposed and alternative choices are discussed. A number of new relations among the parameters of the various reduced forms of the effective Hamiltonian is predicted. Copyright 1999 Academic Press.

Journal Article↗