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Biomedical subjects

G Deutsch

Publications and source records attributed to G Deutsch.

At least 19 recordsLinked to original sources

A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer.

The neuropsychological performance of 85 women with early stage breast cancer scheduled for chemotherapy, 43 women scheduled for endocrine therapy and/or radiotherapy and 49 healthy control subjects was assessed at baseline (T1), postchemotherapy (or 6 months) (T2) and at 18 months (T3). Repeated measures analysis found no significant interactions or main effect of group after controlling for age and intelligence. Using a calculation to examine performance at an individual level, reliable decline on multiple tasks was seen in 20% of chemotherapy patients, 26% of nonchemotherapy patients and 18% of controls at T2 (18%, 14 and 11%, respectively, at T3). Patients who had experienced a treatment-induced menopause were more likely to show reliable decline on multiple measures at T2 (OR=2.6, 95% confidence interval (CI) 0.823-8.266 P=0.086). Psychological distress, quality of life measures and self-reported cognitive failures did not impact on objective tests of cognitive function, but were significantly associated with each other. The results show that a few women experienced objective measurable change in their concentration and memory following standard adjuvant therapy, but the majority were either unaffected or even improve over time.

Adult↗

Composition dependence of vesicle morphology and mixing properties in a bacterial model membrane system.

We have determined the mixing properties and lamellar organization of bacterial membrane mimetics composed of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) and -phosphatidylglycerol (POPG) at various molar ratios applying differential scanning calorimetry, small and wide-angle X-ray scattering, as well as optical phase contrast microscopy. Combining the experimental thermodynamic data with a simulation of the liquidus and solidus lines, we were able to construct a phase diagram. Using this approach, we find that the lipids mix in all phases non-ideally in the thermodynamic sense. As expected, pure POPE assembles into multilamellar and pure POPG into unilamellar vesicles, respectively, which are stable within the studied temperature range. In contrast, mixtures of the two components form oligolamellar vesicles consisting of about three to five bilayers. The layers within these oligolamellar liposomes are positionally correlated within the gel phase, but become uncorrelated within the fluid phase exhibiting freely fluctuating bilayers, while the vesicles as a whole remain intact and do not break up into unilamellar forms. X-ray, as well as DSC data, respectively, reveal a miscibility gap due to a lateral phase segregation at POPG concentrations above about 70 mol%, similar to previously reported data on mixtures composed of disaturated PEs and PGs. Hence, the existence of a region of immiscibility is a general feature of PE/PG mixtures and the mixing properties are dominated by PE/PG headgroup interactions, but are largely independent of the composition of the hydrocarbon chains. This is in accordance with a recent theoretical prediction.

Bacteria↗

High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer.

BACKGROUND: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. PATIENTS AND METHODS: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles (3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. RESULTS: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses (median cumulative dose 339 mg/m(2)) was administered (range: 2-18). The overall response rate was 48.1% (95% CI: 34-61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months (intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. CONCLUSION: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status.

Adult↗

The effects of adjuvant chemotherapy on cognition in women with breast cancer--preliminary results of an observational longitudinal study.

Several studies have reported that chemotherapy-treated patients have impaired cognition function relative to control groups. We are conducting a longitudinal study with cognitive assessments at baseline, 6 and 18 months. A planned preliminary analysis of data from 50 chemotherapy patients and 43 healthy controls at baseline and post-treatment found a significant group by time interaction on three measures of verbal and working memory. Chemotherapy patients were more likely to show cognitive decline than controls (OR 2.25). Patients were significantly more likely to have GHQ(12) scores indicative of possible psychological morbidity and showed significant increases in endocrine symptoms and fatigue post-treatment however neither GHQ(12) nor quality-of-life variables were related to cognitive performance.

Antineoplastic Combined Chemotherapy Protocols↗

A bipotential precursor population for pancreas and liver within the embryonic endoderm.

The pancreas emerges independently from dorsal and ventral domains of embryonic gut endoderm. Gene inactivation experiments in mice have identified factors required for dorsal pancreas development, but factors that initiate the ventral pancreas have remained elusive. In this study, we investigated the hypothesis that the emergence of the ventral pancreas is related to the emergence of the liver. We find that the liver and ventral pancreas are specified at the same time and in the same general domain of cells. Using embryo tissue explantation experiments, we find that the default fate of the ventral foregut endoderm is to activate the pancreas gene program. FGF signalling from the cardiac mesoderm diverts this endoderm to express genes for liver instead of those for pancreas. No evidence was found to indicate that the cell type choice for pancreas or liver involves a selection for growth or viability. Cardiac mesoderm or FGF induces the local expression of sonic hedgehog, which in turn is inhibitory to pancreas but not to liver. The bipotential precursor cell population for pancreas and liver in embryonic development and its fate selection by FGF has features that appear to be recapitulated in the adult pancreas and are reflected in the evolution of these organs.

Animals↗

Use of neuroimaging to understand abnormal pain sensitivity in fibromyalgia.

This paper examines the use of neuroimaging to measure change in regional cerebral blood flow (rCBF) produced by pain in patients with fibromyalgia and in healthy individuals. Fibromyalgia patients differ from healthy persons in rCBF distribution in several brain structures involved in pain processing and pain modulation both at rest and during experimental pain induction. These abnormalities may contribute to abnormal pain sensitivity as well as the maladaptive pain behaviors that characterize many patients with fibromyalgia. We anticipate that future neuroimaging studies will enhance our understanding of abnormal pain sensitivity and of pain management interventions aimed at altering central nervous system function in patients with fibromyalgia.

Blood Flow Velocity↗

Efficient genetic analysis of fungal samples.

We present a method for rapid genetic analysis of small amounts of fungal material. Sterile glass slides, sufficiently small to fit in a standard PCR tube, were placed on agar inside a Petri dish. After a few days, fungal cultures start to overgrow the glass slides. Glass slides with attached mycelium were harvested, analysed microscopically, and placed into a standard PCR tube. Conserved primers flanking the ITS regions of rDNA repeat were used in a direct PCR with the fungal material. Sequence data were generated to be included in phylogenetic analyses to investigate the relationships of the studied mycorrhizal fungi from orchids. The mycelium attached to glass slides was also used for an in situ hybridization experiment using fluorescent labelled oligonucleotides as probes. Fluorescent signal was found throughout the cytoplasm when a probe specific to a site in the nuclear small subunit rRNA is used.

DNA Primers↗

Evaluation of patient satisfaction in a specialized HIV/AIDS care unit of a major hospital.

Patient satisfaction has gained widespread recognition as an important indicator of quality of care. In this study, we analyzed quality of care in correlation with patient satisfaction. Our results indicate that the overall satisfaction of quality of care of HIV/AIDS patients in a dedicated HIV/AIDS unit is affected mainly by the patient's perception of his/her health status, level of professional or family support, and the patient's level of involvement in treatment decisions.

HIV Infections↗

Angiogenesis and morphogenesis of murine fetal distal lung in an allograft model.

Neovascularization is crucial to lung morphogenesis; however, factors determining vessel growth and formation are poorly understood. The goal of our study was to develop an allograft model that would include maturation of the distal lung, thereby ultimately allowing us to study alveolar development, including microvascular formation. We transplanted 14-day gestational age embryonic mouse lung primordia subcutaneously into the back of nude mice for 3.5-14 days. Lung morphogenesis and neovascularization were evaluated by light microscopy, in situ hybridization, and immunohistochemical techniques. Embryonic 14-day gestational age control lungs had immature structural features consistent with pseudoglandular stage of lung development. In contrast, 14 days after subcutaneous transplantation of a 14-day gestational age lung, the allograft underwent significant structural morphogenesis and neovascularization. This was demonstrated by continued neovascularization and cellular differentiation, resulting in mature alveoli similar to those noted in the 2-day postnatal neonatal lung. Confirmation of maturation of the allograft was provided by progressive type II epithelial cell differentiation as evidenced by enhanced local expression of mRNA for surfactant protein C and a threefold (P < 0.008) increase in vessel formation as determined by immunocytochemical detection of platelet endothelial cell adhesion molecule-1 expression. Using the tyrosine kinase Flk-1 receptor (flk-1) LacZ transgene embryos, we determined that the neovascularization within the allograft was from the committed embryonic lung endothelium. Therefore, we have developed a defined murine allograft model that can be used to study distal lung development, including neovascularization. The model may be useful when used in conjunction with an altered genetic background (knockout or knock in) of the allograft and has the further decided advantage of bypassing placental barriers for introduction of pharmacological agents or DNA directly into the lung itself.

Animals↗

Frontotemporal decreases in rCBF correlate with degree of dysnomia in primary progressive aphasia.

UNLABELLED: Primary progressive aphasia (PPA) is an uncommon degenerative dementia characterized by gradual impairment of language function with initial sparing of the memory domain. Using semiquantitative 99mTc-hexamethyl propyleneamine oxime (HMPAO) brain SPECT as a measure of regional cerebral blood flow (rCBF), we investigated the relationship between reduced 99mTc-HMPAO uptake and the severity of dysnomia in PPA. METHODS: Seven right-handed patients with PPA had their dysnomia assessed by the Boston Naming Test (BNT), a subtest of the Boston Diagnostic Aphasia Examination. Neuroimaging studies, including 99mTc-HMPAO brain SPECT, CT, and MRI, were performed. Correlational analysis between reduced rCBF and BNT was performed. RESULTS: Brain SPECT showed a reduction in 99mTc-HMPAO uptake involving the frontal and temporal lobes in all 7 patients. CT and MRI showed mild to moderate cerebral atrophy in 4 patients. Low scores on the BNT correlated with low frontotemporal 99mTc-HMPAO (Spearman r = 0.97, P = 0.004) in the 5 patients with left-hemisphere involvement. CONCLUSION: Decreased rCBF to the frontotemporal region characterized the cerebral abnormalities associated with PPA. The finding of focal rCBF abnormalities in the right hemisphere of 2 right-handed women corroborates that PPA symptoms may arise from a "non-left-dominant"-hemisphere degenerative process. Our results support the usefulness of rCBF SPECT imaging as a diagnostic aid in PPA.

Aged↗

Postinfectious cerebellitis: clinical significance of Tc-99m HMPAO brain SPECT compared with MRI.

PURPOSE: We compared Tc-99m HMPAO brain SPECT and MRI with the clinical findings in a case of a 14-year-old boy with post-infectious cerebellitis. RESULTS: Tc-99m HMPAO brain SPECT scan showed marked reduction in perfusion to the left anterior lobe, left lateral hemisphere, and left posterior lobe of the cerebellum. The MRI showed a limited region of abnormal signal in the mid posterior left cerebellar hemisphere. Since the patient's overall neurological deficit was characterized by ataxia, nystagmus, head and body titubation, dysmetria, dysdiadochokinesia, loss of normal check, and rebound testing attributed to the involvement of the anterior, lateral, and posterior lobes of the left cerebellar hemisphere, the Tc-99m HMPAO brain SPECT finding correlated better with the extent of functional neurological deficits. CONCLUSION: Tc-99m HMPAO brain SPECT may better assess cerebellar signs and symptoms in cerebellitis since the blood flow abnormalities correlated with dysfunction of the cerebellum, whereas the MRI abnormalities did not encompass the scope of the neurological deficits.

Adolescent↗

Familial painful restless legs syndrome correlates with pain dependent variation of blood flow to the caudate, thalamus, and anterior cingulate gyrus.

To understand the relationship of caudate, thalamic, and anterior cingulate perfusion to pain states, we investigated familial restless legs syndrome in a father and daughter during the state of pain induced by immobility using semiquantitative regional cerebral blood flow (rCBF) brain single photon emission computed tomography (SPECT). The father underwent 4 brain SPECT scans using the rCBF tracer 99mTc-HMPAO several weeks apart, at different pain levels and after treatment with L-dopa. Caudate, thalamic, and anterior cingulate rCBF indices were measured. The caudate nuclei showed a 13% reduction in rCBF with increasing pain. The thalami and anterior cingulate showed a 7 and 6.6% increase in rCBF, respectively, with increasing pain. Compared to normal controls at rest, there was a decrease in caudate rCBF by 13% and an increase in thalamic rCBF by 3%. Linear regression for the caudate nuclei revealed a significant reduction in rCBF (p < 0.05), as pain increased. The daughter underwent an identical rCBF brain SPECT scan procedure at a high pain level induced by immobilization. Her scan showed a 12% reduction in caudate rCBF and a 1.2% increase in the anterior cingulate rCBF compared to healthy controls. The study supports the association between pain and decreased regional cerebral blood flow to the caudate nucleus as reported in fibromyalgia syndrome. There is increase in anterior cingulate rCBF with increasing pain. Our findings also corroborate that there is increased thalamic rCBF with pain stimulation.

Adult↗

Jejunal cirsoid aneurysm: a rare cause of massive lower gastrointestinal hemorrhage.

Diverticulosis and angiodysplasia are the most common causes of massive lower gastrointestinal hemorrhage. Lower gastrointestinal hemorrhage frequently resolves without determination of a definitive source. An uncommon cause of lower gastrointestinal tract hemorrhage is the small intestinal submucosal aneurysm. This poorly described entity, more commonly recognized as Dieulafoy's disease in the gastric mucosa, has been documented only rarely in the jejunum. We describe a case report of a 27-year-old man with a massive lower gastrointestinal hemorrhage. Diagnostic evaluation failed to identify the source on initial admission. The patient re-presented to the emergency room with recurrent bleeding, anemia, and hypotension. During a period of active bleeding, a number of diagnostic studies ultimately revealed the source to be the proximal jejunum. Inspection of the resected specimen identified a submucosal aneurysm on the mesenteric border. Histologic evaluation identified the pathologic entity as a cirsoid aneurysm.

Adult↗

A semiquantitative cortical circumferential normalization method for clinical evaluation of rCBF brain SPECT.

The authors studied 33 normal patients who ranged in age from 8 to 71 years to establish a normative data base for young-age, middle-age, and older-age subjects using a computer automated semi-quantitative cortical annular region of interest (ROI) method. The data were grouped to obtain a "young age-range" normative data base of mean age +/- 1 S.D. = 13.1 +/- 4.8 years (seven subjects with an age range of 6 to 20 years); a "middle age-range" normative data base of mean age +/- 1 S.D. = 39 +/- 2.7 years (12 subjects with an age range of 35 to 43 years); and an "older age-range" normative data base of mean age +/- 1 S.D. = 59.7 +/- 5.8 years (14 subjects with an age range of 55 to 71 years). Normative values were obtained for brain level parallel to and positioned at 3.5, 5.5, and 7.5 cm above the canthomeatal (CM) line. The results show that the average global rCBF indices (defined as cortical/cerebellar ratios) for the young age-range group were 0.98, 0.99, 1.07; middle age-range group were 0.84, 0.86, and 0.88; and older age-range group were 0.86, 0.87 and 0.87 for CM + 3.5 cm, CM + 5.5 cm, and CM + 7.5 cm, respectively. In routine clinical studies, on more then 2,000 Tc-99m HMPAO brain SPECT scans, the authors have employed this semi-quantitative cortical circumferential normalization method of analysis to accurately calculate indices representing cortical blood flow values. This method also allows efficient comparison of individual patient values to age-range matched normal control groups to assist in disease diagnosis.

Adolescent↗

Regional stability of cerebral blood flow measured by repeated technetium-99m-HMPAO SPECT: implications for the study of state-dependent change.

UNLABELLED: The replicability of resting state rCBF has implications for the analysis of cerebral activation protocols and the interpretation of rCBF in disease states. This study examined the stability of rCBF as measured by two resting state 99mTc-HMPAO brain SPECT scans with an emphasis on examining the contribution of specific cerebral regions to within and between subjects variance. METHODS: Nine normal, medically healthy subjects underwent two 99mTc-HMPAO brain SPECT scans under identical conditions separated by 48 hr. A reference system and semiautomated computer ROI method was used to enable accurate alignment and cortical analysis of the two scans. RESULTS: Mean within-subject difference between Scans 1 and 2 was 2.8% (range 0%-7.8%) for the 36 cortical ROIs. The mean between-subject coefficient of variation was 10% (range 7%-15%) for these ROIs. Correlation analysis of rCBF pattern replication for all slice levels yielded a highly significant overall consistency of pattern within subjects (Pearson r = 0.698, p = 0.0001). Variance component analysis revealed regional heterogeneity in between-subjects variance, with significantly greater variability found in frontal regions. The within-subject repeated measures variability was not significantly different across regions. CONCLUSION: Good within-subject 48-hr replicability indicates that individual resting state rCBF reflects fairly stable, subject-specific factors. This also justifies comparing state-dependent studies separated by a modest length of time. Although individual patterns of rCBF replicate well, the larger contribution of frontal regions to normal between-subjects variance makes evaluating the frontal effects of disease or activation more difficult.

Aged↗