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Biomedical subjects

B Thiessen

Publications and source records attributed to B Thiessen.

18 recordsLinked to original sources
PubMed2006

Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis.

OBJECTIVE: To report the presence of microscopic neoplasms of the testis in men with anti-Ma2-associated encephalitis (Ma2-encephalitis) and to discuss the clinical implications. METHODS: Orchiectomy specimens were examined using immunohistochemistry with Ma2 and Oct4 antibodies. RESULTS: Among 25 patients with Ma2-encephalitis younger than 50 years, 19 had germ-cell tumors, and 6 had no evidence of cancer. These 6 patients underwent orchiectomy because they fulfilled five criteria: 1) demonstration of anti-Ma2 antibodies in association with MRI or clinical features compatible with Ma2-encephalitis, 2) life-threatening or progressive neurologic deficits, 3) age < 50 years, 4) absence of other tumors, and 5) new testicular enlargement or risk factors for germ-cell tumors, mainly cryptorchidism or ultrasound evidence of testicular microcalcifications. All orchiectomy specimens showed intratubular-germ cell neoplasms unclassified type (IGCNU) and other abnormalities including microcalcifications, atrophy, fibrosis, inflammatory infiltrates, or hypospermatogenesis. Ma2 was expressed by neoplastic cells in three of three patients examined. Even though most patients had severe neurologic deficits at the time of orchiectomy (median progression of symptoms, 10 months), 4 had partial improvement and prolonged stabilization (8 to 84 months, median 22.5 months) and two did not improve after the procedure. CONCLUSIONS: In young men with Ma2-encephalitis, 1) the disorder should be attributed to a germ-cell neoplasm of the testis unless another Ma2-expressing tumor is found, 2) negative tumor markers, ultrasound, body CT, or PET do not exclude an intratubular germ-cell neoplasm of the testis, and 3) if no tumor is found, the presence of the five indicated criteria should prompt consideration of orchiectomy.

Adult↗
PubMed2005

Inhibition of ILK in PTEN-mutant human glioblastomas inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth.

The tumor suppressor gene phosphatase and tensin homologue (PTEN) regulates the phosphatidylinositol-3'-kinase (PI3K) signaling pathway and has been shown to correlate with poor prognosis in high-grade astrocytomas when mutational inactivation or loss of the PTEN gene occurs. PTEN mutation leads to constitutive activation of protein kinase B (PKB)/Akt with phosphorylation at the PKB/Akt sites Thr-308 and Ser-473. Integrin-linked kinase (ILK) has been shown to regulate PKB/Akt activity with the loss of PTEN in prostate cancer. We now demonstrate that ILK activity regulates PKB/Akt activity in glioblastoma cells. The activity of ILK is constitutively elevated in a serum-independent manner in PTEN mutant cells, and transfection of wild-type PTEN under the control of an inducible promoter into mutant PTEN cells inhibits ILK activity. Transfection of ILK antisense (ILKAS) or exposure to a small-molecule ILK inhibitor suppresses the constitutive phosphorylation of PKB/Akt on Ser-473 in PTEN-mutant glioblastoma cell lines. In addition, the delivery of ILKAS to PTEN-negative glioblastoma cells resulted in apoptosis. Rag-2M mice bearing established ( approximately 100 mg) human U87MG glioblastoma tumors, treated QD x 5 for 3 consecutive weeks with ILKAS (i.p. 5 mg/kg), exhibited stable disease with < or =7% increase in tumor volume over the 3-week course of treatment. In contrast, animals treated with an oligonucleotide control or saline exhibited a >100% increase in tumor volume over the same time period. Our initial results indicate that therapeutic strategies targeting ILK may be beneficial in the treatment of glioblastomas.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2000

Evaluation of early response to SU101 target-based therapy in patients with recurrent supratentorial malignant gliomas using FDG PET and Gd-DTPA MRI.

Changes in [18F]-2-fluoro-2-deoxyglucose (FDG) uptake and gadopentetate dimeglumine (Gd-DTPA) enhancement before and after the first course of treatment with a cytostatic agent SU101 (N-[(4-trifluoromethyl)-phenyl]-5-methylisoxazole-4-carboxamide, SUGEN) were assessed using positron emission tomography (PET) and magnetic resonance imaging (MRI) in a pilot study of 8 patients with recurrent supratentorial malignant gliomas. The localization and the volume of Gd-DTPA enhancement and FDG hypermetabolism were analyzed. PET and MRI studies were performed one week before and 7.6+/-3.7 weeks after administration of SU101. The ratios of mean tumor activity to mean contralateral white matter and ipsilateral cerebellar activity were calculated for tumor regions, and SUV values corrected to the subjects' body surface area and glucose level (SUVbsa*glu) were calculated for nontumor regions. Five patients had a substantial increase of tumor volume on both PET and MRI during the first course of SU101. PET and MRI showed roughly equivalent volume changes. Large tumor volume increases were associated with a short time to clinical progression. The metabolic change in the tumor following the first course of SU101 varied from patient to patient, ranging from a 31% reduction to a 43% increase in FDG uptake ratio. Changes in FDG uptake were not predictive of time to progression or survival. In 2 patients with marked clinical deterioration and rapid tumor growth, there were differences in localization of Gd-DTPA enhancement and FDG hypermetabolism suggesting that hypermetabolism beyond the area of contrast enhancement may be of value in predicting rapid progression of high-grade glioma. SU101 did not induce any appreciable changes in SUVbsa*glu for non-tumor brain in 6 of 8 patients.

Adult↗
PubMed1998

Hydrocephalus in radiation leukoencephalopathy: results of ventriculoperitoneal shunting.

OBJECTIVE: To assess the clinical benefit of ventriculoperitoneal shunting in patients suffering from radiotherapy-induced leukoencephalopathy. DESIGN: Retrospective review of a single institutional experience. PATIENTS: Thirty-one patients with the postradiotherapy syndrome received ventriculoperitoneal shunts. All had a history of cranial irradiation, progressive ventriculomegaly visible on neuroimaging scans, and neurologic decline; other causes of hydrocephalus were excluded. All 31 patients had cognitive deficits: 30 had gait disturbance and 24 were incontinent. RESULTS: Twenty-four (80%) of 30 assessable patients achieved symptomatic improvement an average of 1.6 months after ventriculoperitoneal shunting. Incontinence and gait problems were more likely to improve than cognition. Sixteen (53%) of 30 patients achieved a good overall functional outcome, and incontinence was the only feature significantly associated with good outcome (P=.04). Neither cerebrospinal fluid-opening pressure nor tap tests predicted improvement from ventriculoperitoneal shunting. Median duration of improvement was 6 months, and median survival after receiving the shunt was 14.5 months. Shunt-related complications occurred in 10 (33%) of 30 patients, with 1 fatal outcome. CONCLUSIONS: Our results from ventriculoperitoneal shunting in selected patients with radiation-induced hydrocephalus suggest potential benefit. Improvement is incomplete and temporary, but can improve quality of life. Reliable predictors of successful shunt outcome were not identified.

Adult↗
PubMed1998

Astroblastoma: does histology predict biologic behavior?

Astroblastoma is a rare and controversial tumor about which little is known. We have made the diagnosis in seven patients since 1990 at Memorial Sloan-Kettering Cancer Center. Four patients had astroblastomas with anaplastic features, whereas three patients had tumors which were well-differentiated. All three patients with low grade lesions are alive and recurrence free after surgery alone (mean follow-up 29 months). All four patients with anaplastic astroblastoma were treated with surgery, radiotherapy and chemotherapy. One died of infection during induction chemotherapy. Two others died of tumor progression at 28 and 42 months. Radiographic response to chemotherapy was seen in one patient. The results of our series and other reports suggest that anaplastic histology is a prognostic factor in the setting of astroblastoma. More aggressive treatment is necessary for patients with anaplastic astroblastoma although the precise role of irradiation and chemotherapy cannot be defined at this time.

Antineoplastic Agents↗
PubMed1997

Fluorodopa and raclopride PET analysis of patients with Machado-Joseph disease.

We performed [18F]6-fluoro-L-dopa (6-FD) and [11C]raclopride (RAC) PET studies in six patients with Machado-Joseph disease (MJD) (age, 17 to 61 years; duration of illness, 3 to 10 years), normal controls (n = 10 in 6-FD-PET, n = 8 in RAC-PET), and patients with idiopathic parkinsonism (n = 15 in 6-FD-PET). The youngest patient with MJD had prominent dystonia and pyramidal features (type 1 MJD), whereas the remainder were prominently ataxic (types 2 and 3 MJD). Striatal RAC binding was normal in patients with MJD. Striatal 6-FD influx constants (Ki) were low in the range of idiopathic parkinsonism in two patients with MJD (youngest and oldest patients), whereas striatal Ki were normal in the remaining patients with MJD. The impairment of the nigrostriatal dopaminergic pathway did not correlate with the phenotype, CAG repeat length, disease duration, or age of onset of patients with MJD. Our results suggest that striatal D2 receptors are normal and the nigral damage is diverse in MJD.

Adolescent↗
PubMed1990

Age, environments, and the number of substantia nigra neurons.

We examined forty-eight midbrain sections from normal brains containing SN at the level of the exiting fibers of the IIIrd cranial nerve. The cases were classified into two groups based on at least 80% life exposure to either rural or urban provincial environments, respectively. Linear regression analysis revealed a lower SN neuron count in the rural group by age 20, although this difference was not statistically significant. There was a 34% decline in urban and a 17% decline in rural residents' neuron counts between ages 20 and 80. These results are consistent with our previous studies, which indicate a higher risk of PD in the Saskatchewan rural population. We believe that studies of environmental factors in early life will provide the most rewarding clues to the etiology of PD.

Adult↗
PubMed1989

Hypersexuality with antiparkinsonian therapy.

Thirteen parkinsonian patients drawn from two large parkinsonism clinics experienced hypersexuality as a consequence of anti-parkinsonian therapy. The cases include only those whose sexual behavior on treatment became a concern to the patient's family or a social agency. The majority of patients were men and had a relatively early onset of parkinsonian symptomatology. There was no relation between functional improvement and increased sexuality. Most patients showed some element of dose dependency between antiparkinsonian drugs and the hypersexual behavior. Prior sexual profile included from no sexual outlet to hypersexuality. Neither the prior history of psychiatric illness nor brain damage predisposed to such response on treatment, and in most patients, it was not a part of hypomania or a more diffuse psychiatric disturbance. We propose that hypersexuality on antiparkinsonian drugs is consequent to inhibition of prolactin secretion.

Adult↗
PubMed1984

Factors determining residual volume in normal and asthmatic subjects.

We have studied the mechanisms determining the residual volume (RV), by inducing temporary changes in RV through respiratory manoeuvres and bronchodilation. Four asthmatic and 5 normal subjects inhaled placebo, salbutamol, and ipratropium bromide, and performed maximum expiratory manoeuvres after partial and maximal inspiration. RV and static lung pressure-volume measurements were made in each experiment. After bronchodilation, RV increased in both groups after a maximal inspiration, while bronchodilatation, as such, decreased RV in both groups. We also found unexpectedly that in the asthmatic patients, the static transpulmonary pressure (Pst) at low lung volumes increased after bronchodilatation. Our findings can be explained if bronchodilators open-up closed airways, and if a preceding maximal inspiration decreases the elastic recoil pressure of the lungs causing a change of the lung volume at which airway closure occurs. The results also support that Pst at low lung volume is influenced by airway closure and underestimates the elastic recoil pressure of the lungs, even in normal subjects. We postulate that the increase in Pst at low lung volumes after bronchodilatation is due to smaller amounts of trapped gas.

Adult↗
PubMed1982

Airway compliance and flow limitation during forced expiration in dogs.

Bronchial pressure measured by means of a Pitot static probe, esophageal pressure, and airflow were monitored during forced lung deflations in six anesthetized dogs. Dynamic transmural pressure-cross-sectional area area curves (Ptm-A curves) were constructed for three intrathoracic tracheal positions and one right lower lobal bronchial position. From the Ptm-A curves the maximal possible flow (Vmax) through the airways at each of the four positions was calculated and compared with the overall maximal flow obtained during the same deflation. The peak of the maximal expiratory flow-volume curve (MEFV curve) equaled the calculated Vmax at more than one position in the trachea but did not reach the Vmax calculated for the more peripheral position. During the transition between the peak and the plateau of the MEFV curve, the Ptm-A curve often changed shape, indicating an abrupt change in the "tube law," probably due to changes in axial tension of the airway. During the flow-volume curve plateau, measured flow was near an estimated Vmax at a single point in the trachea. At lower lung volumes where the MEFV curve descends from the plateau, measured flow equaled Vmax calculated for the right lower lobe position. This indicates that after an initial period with no localized choking a "choke point" develops and eventually moves toward the periphery. We conclude that measurement of dynamic Ptm-A curves allows a precise prediction of maximal expiratory flows from the properties of the airways.

Animals↗
PubMed1982

Maximal expiratory flows and forced vital capacity in normal, asthmatic and bronchitic subjects after salbutamol and ipratropium bromide.

A total of 2,880 maximum expiratory flow-volume curves were performed in a controlled double-blind cross-over examination designed to evaluate the bronchodilating effects of two different nebulized doses of salbutamol (1.75 and 0.875 mg) and ipratropium bromide (0.175 and 0.0875 mg) inhaled by 8 normal, 8 asthmatic, and 8 bronchitic subjects. FEV1, FVC, and flows at 50% FVC and at three fixed volumes below TLC have been measured over a period of 6 h on the maximum expiratory flow-volume curve. In the normal subjects, salbutamol seems to have a smaller bronchodilating effect than ipratropium bromide both at high and low lung volumes. After salbutamol the average initial FEV1 increased from 4.0 to 4.3 liters, whereas after ipratropium bromide it increased to 4.4 liters. In our asthmatic patients the initial response to salbutamol was much larger than to ipratropium bromide. After salbutamol FEV1 increased from 1.8 to 2.7 liters in 60 min, whereas after ipratropium bromide it increased to 2.4 liters in 120 min. In our bronchitic patients the difference between the two drugs seems to be very small. After both drugs FEV1 increased from 1.6 to 2.1 liters. The choice of drug for treatment of the condition would then depend on how well the individual patients tolerate the two drugs.

Adult↗
PubMed1980

Effect of freon inhalation on maximal expiratoryflows and heart rhythm after treatment with salbutamol and ipratropium bromide.

The purpose of this investigation was to determine whether inhalation of a freon gas mixture, the propellant of the commercial metered-dose aerosols, consisting of freon 11, freon 12, and freon 114, reduces the bronchodilating effects of inhaled salbutamol or ipratropium bromide or causes cardiac arrhythmias in control, asthmatic and bronchitic subjects. FEV1 and flows measured at different lung volumes on the maximal effort expiratoryflow-volume curve were measured during a period of 6 h. Inhalation of freon caused no significant overall reduction in the salbutamol and ipratropium bromide response in any group. Arrhythmias only occurred among the asthmatic and bronchitic patients, and were most frequent after salbutamol. Ventricular extrasystoles occurred in three cases, all after salbutamol and in two of these in combination with freon inhalation. In one patient there was furthermore hyposia and hypercapnia. The combination of the effects of hypoxia, hypercapnia, catecholamines and freon on the heart is therefore a more likely cause of arrhythmia than the effect of freon alone.

Adult↗
PubMed1979

A double blind cross-over study of maximal expiratory flows and arterial blood gas tensions in normals, asthmatics and bronchitics after salbutamol and ipratropin.

8 normals, 8 asthmatics and 8 bronchitics inhaled comparable doses of ipratropin and salbutamol. Five different flow-volume parameters were measured before and at intervals from 3 to 360 minutes after inhalation, on a total number of 2880 maximal effort expiratory flow-volume curves. Arterial blood gas tensions were measured before and 60 minutes after inhalation. In all parameters a significant larger effect (p less than 0.05) of ipratropin was found in normals, but in different time intervals. The parameter FEV1 and MEF at 50% of FVC showed the largest effect of salbutamol during the interval from 3 to 60 minutes in the asthma patients. None of the parameters showed significant difference in drug effects in the bronchitis patients. The findings suggested a more peripheral action of ipratropin than of salbutamol in the normals. No significant change in gas tensions were found after inhalation in any of the three groups.

Albuterol↗
PubMedDate not supplied

Comparison of gastrointestinal tolerance to two enteral feeding protocols in critically ill patients: a prospective, randomized controlled trial.

BACKGROUND: The purpose of this study was to compare gastrointestinal tolerance to two enteral feeding protocols in critically ill patients. METHODS: A prospective, randomized controlled trial, that involved 96 consecutive patients expected to stay in the intensive care unit for > or =3 days and who had no contraindications to enteral feeding. The patients were randomized to either the current protocol (group I; gastric residual volume threshold, 150 mL, optional prokinetic) or proposed feeding protocol (group II; gastric residual volume threshold 250 mL, mandatory prokinetic). Gastrointestinal intolerance was recorded as episodes of high gastric residual volume, emesis, or diarrhea. The time to reach the goal rate of feeding and the percentage of nutritional requirements received during the study period were also recorded. RESULTS: Nineteen of 36 patients (19/36 = 0.53) in group I had one or more episodes of high gastric residual volume, compared with 10 of 44 patients (10/44 = 0.23) in group II (p < .005). There was no statistical difference between the two protocols with regards to emesis, diarrhea, or the total episodes of intolerance. The patients in group II reached their goal rates on average in 15 hours and received 76% of their nutritional requirements, compared with 22 hours and 70% in group I; however, these differences were not statistically significant. CONCLUSIONS: The incidence of enteral feeding intolerance was reduced by using a gastric residual volume of 250 mL along with the mandatory use of prokinetics. The study showed a trend of improved enteral nutrition provision and reduced the time to reach the goal rate in group II. These improvements support the adoption of the proposed feeding protocol for critically ill patients.

Adult↗