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Biomedical subjects

J Kessler

Publications and source records attributed to J Kessler.

At least 19 recordsLinked to original sources

Ductus venosus shunting in growth-restricted fetuses and the effect of umbilical circulatory compromise.

OBJECTIVE: To determine the degree of ductus venosus (DV) shunting in fetuses with intrauterine growth restriction (IUGR) and the effect of various degrees of umbilical circulatory compromise. METHODS: This was a cross-sectional observational study. Sixty-four fetuses with IUGR (estimated weight < or = 2.5(th) percentile) underwent ultrasound examination. The diameter, velocity, and blood flow were determined in the DV and intra-abdominal umbilical vein (UV), and the fraction of shunting and DV : UV diameter ratios were calculated. Placental compromise was classified according to either normal umbilical artery (UA) pulsatility index (PI), UA-PI > 97.5(th) percentile, or absent or reversed end-diastolic flow velocity (A/REDV). Regression analysis was used to construct mean values, and SD scores were used to determine differences compared with a reference population (n = 212) after ln- or power-transformation. RESULTS: In the 64 growth-restricted fetuses, the average DV shunting was 39% compared with 25% in the reference group (overall P < 0.0001). The corresponding values in the subgroups with normal UA-PI, UA-PI > 97.5(th) percentile, and A/REDV were 31%, 35%, and 57%, respectively. Fetuses with IUGR and normal UA-PI (SD score: mean, 0.48; 95% CI, 0.04-0.92) did not shunt significantly more than did the reference fetuses (SD score: mean, 0.0; 95% CI, - 0.15 to 0.15), but those with UA-PI > 97.5(th) percentile (SD score: mean, 0.85; 95% CI, 0.41-1.29), and particularly those with A/REDV (SD score: mean, 1.56; 95% CI, 1.0-2.12) did shunt significantly more. With more DV shunting, these fetuses distributed correspondingly less umbilical blood to the liver, one of the mechanisms being a lower perfusion pressure as reflected in the lower DV blood velocity (P < 0.0001). CONCLUSIONS: DV shunting is higher and the umbilical blood flow to the liver is less in fetuses with IUGR, particularly in those with the most severe umbilical hemodynamic compromise.

Blood Flow Velocity↗

Fetal cardiac output, distribution to the placenta and impact of placental compromise.

OBJECTIVES: Intrauterine growth restriction is a common clinical problem, but the underlying hemodynamic changes are not well known. Our aim was to determine the normal distribution of fetal cardiac output to the placenta during the second half of pregnancy, and to assess the changes imposed by growth restriction with various degrees of placental compromise. METHODS: A cross-sectional study of 212 low-risk pregnancies with a gestational age of 18-41 weeks constituted the reference population. A second group of 64 pregnancies with an estimated fetal weight 97.5th percentile, or absent/reversed end-diastolic velocity. Regression analysis and Z-score (SD-score) statistics were used to establish normal ranges and to compare groups. RESULTS: During gestational weeks 18-41 the normal CCO/kg was on average 400 mL/min/kg and the fraction directed to the placenta was on average 32%, while after 32 weeks it was 21%. In intrauterine growth restriction the CCO/kg was not significantly different, but the fraction to the placenta was lower (P < 0.001). This effect was more pronounced in severe placental compromise (P < 0.001). CONCLUSIONS: Normally, one third of the fetal CCO is distributed to the placenta in most of the second half of pregnancy, and one fifth near term. In placental compromise this fraction is reduced while CCO/kg is maintained at normal levels, signifying an increased recirculation of umbilical blood in the fetal body.

Aorta↗

Longitudinal reference ranges for ductus venosus flow velocities and waveform indices.

OBJECTIVES: Serial Doppler measurements of the ductus venosus are used increasingly for monitoring fetuses at risk of hemodynamic compromise, but existing reference ranges are based on cross-sectional studies and thus are less suitable for comparison with serial measurements. We aimed to establish longitudinal reference ranges for ductus venosus flow velocities and waveform indices and to provide the necessary terms for calculating conditional reference ranges for serial measurements. METHODS: This was a longitudinal study of 160 low-risk pregnancies. Pulsed Doppler ultrasound was used to record ductus venosus blood flow velocities at 4-week intervals from 20-22 weeks of gestation onwards. RESULTS: With a success rate of 93%, 547 measurements (four or five in each fetus) were used to establish reference ranges. The time-averaged maximum velocity was 50 cm/s at 21 weeks of gestation, increased to 60 cm/s at 32 weeks, and remained so until term. Similarly, the peak systolic velocity increased from 59 cm/s at 21 weeks to 71 cm/s at 31 weeks and remained so until term. The end-diastolic velocity showed a continuous increase from 31 cm/s at 21 weeks to 43 cm/s at 40 weeks. The pulsatility index for veins decreased from 0.57 at 21 weeks to 0.44 at 40 weeks. When conditioned by a previous measurement, the reference ranges for the next observation became narrower and commonly shifted compared with those of the entire population. CONCLUSION: The new longitudinal reference ranges presented here reflect the development of the ductus venosus flow velocities and velocity indices and are thus appropriate for serial measurements, particularly if conditional terms are included.

Adult↗

Laparoscopic colon resection for polyps: a good novice case?

PURPOSE: Laparoscopic colon resection of the endoscopically unresectable polyp has been considered an ideal case for the surgeon with moderate laparoscopic colectomy experience because tissues are not inflamed and the lymphadenectomy may not need to be as extensive compared with that required for cancer. To assess the appropriateness of this approach, we evaluated the incidence of invasive cancer in a series of laparoscopic colon resections for polyps. METHODS: A retrospective review was performed of 55 consecutive patients undergoing laparoscopic colon resection for endoscopically unresectable polyps during a 35-month period. Colonoscopy data, polyp characteristics, and final colon pathology were reviewed. RESULTS: On final pathologic examination, 18.2 percent of patients had invasive adenocarcinoma. Patient age, gender, indication for colonoscopy, polyp size, polyp location, polyp characteristics, and colonoscopic biopsy pathology were not predictive of adenocarcinoma on final pathology. CONCLUSIONS: A significant number of endoscopically unresectable polyps harbor adenocarcinoma, thereby requiring a formal lymphadenectomy at resection. Caution should be exercised when considering the laparoscopic resection of an endoscopically unresectable polyp as a "learning" case.

Adenocarcinoma↗

Martian CH(4): sources, flux, and detection.

Recent observations have detected trace amounts of CH(4) heterogeneously distributed in the martian atmosphere, which indicated a subsurface CH(4) flux of ~2 x 10(5) to 2 x 10(9) cm(2) s(1). Four different origins for this CH(4) were considered: (1) volcanogenic; (2) sublimation of hydrate- rich ice; (3) diffusive transport through hydrate-saturated cryosphere; and (4) microbial CH(4) generation above the cryosphere. A diffusive flux model of the martian crust for He, H(2), and CH(4) was developed based upon measurements of deep fracture water samples from South Africa. This model distinguishes between abiogenic and microbial CH(4) sources based upon their isotopic composition, and couples microbial CH(4) production to H(2) generation by H(2)O radiolysis. For a He flux of approximately 10(5) cm(2) s(1) this model yields an abiogenic CH(4) flux and a microbial CH(4) flux of approximately 10(6) and approximately 10(9) cm(2) s(1), respectively. This flux will only reach the martian surface if CH(4) hydrate is saturated in the cryosphere; otherwise it will be captured within the cryosphere. The sublimation of a hydrate-rich cryosphere could generate the observed CH(4) flux, whereas microbial CH(4) production in a hypersaline environment above the hydrate stability zone only seems capable of supplying approximately 10(5) cm(2) s(1) of CH(4). The model predicts that He/H(2)/CH(4)/C(2)H(6) abundances and the C and H isotopic values of CH(4) and the C isotopic composition of C(2)H(6) could reveal the different sources. Cavity ring-down spectrometers represent the instrument type that would be most capable of performing the C and H measurements of CH(4) on near future rover missions and pinpointing the cause and source of the CH(4) emissions.

Atmosphere↗

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment.

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.

Aged↗

Limits for the central production of Theta+ and Xi(--)pentaquarks in 920-GeV pA collisions.

We have searched for Theta+(1540) and Xi(--)(1862) pentaquark candidates in proton-induced reactions on C, Ti, and W targets at midrapidity and square root of s = 41.6 GeV. In 2 x 10(8) inelastic events we find no evidence for narrow (sigma approximately 5 MeV) signals in the Theta+ --> pK0(S) and Xi(--) --> Xi- pi- channels; our 95% C.L. upper limits (UL) for the inclusive production cross section times branching fraction B dsigma/dy/(y approximately 0) are (4-16) mub/N for a Theta+ mass between 1521 and 1555 MeV, and 2.5 mub/N for the Xi(--). The UL of the yield ratio of Theta+/Lambda(1520) < (3-12)% is significantly lower than model predictions. Our UL of B Xi(--)/Xi(1530)0 < 4% is at variance with the results that have provided the first evidence for the Xi(--).

Journal Article↗

DemTect: a new, sensitive cognitive screening test to support the diagnosis of mild cognitive impairment and early dementia.

OBJECTIVES: To design a new, highly sensitive psychometric screening to identify patients with mild cognitive impairment (MCI) and patients with dementia in the early stages of the disease. METHODS: Five tasks were included in the DemTect: a word list, a number transcoding task, a word fluency task, digit span reverse, and delayed recall of the word list. The normation was performed with 145 healthy control subjects (CG). Furthermore, 97 MCI patients and 121 patients with possible Alzheimer's disease (AD) were tested with the DemTect and the MMSE. Classification rates for both tests were analysed. RESULTS: On the basis of the CG data, age-dependant transformation algorithms for the DemTect subtests were defined, and an education correction was provided for the total transformed score. The patient groups scored significantly below the CG in both the DemTect and the MMSE. Compared to the MMSE, classification rates of the DemTect were superior for both the MCI and the AD group, with high sensitivities of 80% and 100%, respectively. CONCLUSIONS: The DemTect is short (8-10 minutes), easy to administer, and its transformed total score (maximum 18) is independent of age and education. The DemTect helps in deciding whether cognitive performance is adequate for age (13-18 points), or whether MCI (9-12 points) or dementia (8 points or below) should be suspected.

Age Factors↗

Activation of basal ganglia loops in idiopathic Parkinson's disease: a PET study.

Patients with idiopathic Parkinson's syndrome (IPS) show dysexecutive deficits which are not related to dementia. We investigated whether these deficits may be caused by a disturbed interaction of prefrontal cortex and selective basal ganglia loops. 5 healthy right-handed volunteers and 5 non demented IPS patients were studied with FDG PET while performing a gambling task paradigm. Control subjects and patients showed consistent bilateral activation of the dorsolateral prefrontal cortex (DLPFC) and the left caudate. Only controls activated the right cingulate, mesial prefrontal and frontoorbital cortex. Patients significantly deactivated the right thalamus. Thus missing frontoorbital and frontomesial activity may indicate an impairment of the basal ganglia loop in IPS, connecting those regions to the thalamus via the ventral striate. The connections between DLPFC and Thalamus via the left caudate remained intact. This impairment may be the neuroanatomical correlate for dysexecutive syndromes in IPS more related to misjudgement than cognitive impairment.

Adult↗

Disturbance and recovery of language function: correlates in PET activation studies.

Disturbance of neurologic function in disorders of the central nervous system is expressed as an altered activation pattern in functional networks employed by specific tasks and can be studied by functional imaging modalities, e.g., positron emission tomography. Language, a complex brain function, is based on the interplay of a distributed network in which partial functions are executed in various centers, the primary language areas. These areas are hierarchically organized and activated according to the complexity of the specific language task. The specialization of different centers and the lateralization of integrative functions into the dominant (usually left) hemisphere are achieved by collateral and transcallosal inhibition of secondary language areas which normally are not employed for performance of a specific language task.

Aphasia↗

Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy.

In part A of this study, patients were randomised to cohorts receiving darbepoetin alfa at doses of 0.5 to 8.0 m.c.g x kg(-1) x wk(-1) or to a control group receiving epoetin alfa at an initial dose of 150 U x kg(-1) three times weekly. In part B, the cohorts were darbepoetin alfa 3.0 to 9.0 m.c.g x kg(-1) every 2 weeks or epoetin alfa, initial dose 40 000 U x wk(-1). Safety was assessed by adverse events, changes in blood pressure, and formation of antibodies to darbepoetin alfa. Efficacy was assessed by several haematologic endpoints, including change in haemoglobin from baseline. The adverse event profile of darbepoetin alfa was similar to that of epoetin alfa. No relationship between the rapidity of haemoglobin response and any adverse event was observed. No antibodies to darbepoetin alfa were detected. Higher doses of darbepoetin alfa increased the proportion of patients with a haemoglobin response and decreased the median time to response. The overall dose of darbepoetin alfa required to produce a mean increase in haemoglobin does not increase when the dosing interval is increased from 1 to 2 weeks. Therapy with darbepoetin alfa is safe and effective in producing a dose-related increase in haemoglobin levels in patients with cancer receiving chemotherapy.

Adult↗

[Number processing and acalculia in dementia].

In this review, studies on number processing and calculation in demented patients are summarized. Single cases, group studies and our own examinations all show that acalculia is a frequent symptom of dementia and correlates with severity of dementia. While calculation and numeral transcoding deficits are often prominent in early courses of the disease, deficits in semantic processing and basic number processing are less severe. Still, single cases demonstrate that very specific dysfunctions in number processing and calculation can occur in dementia. In number transcoding, a characteristic error type occurs in demented patients that has not (or rarely) been described in other brain damaged people so far. In these "shift errors" or "intrusion errors" the wrong number code is used or the number codes are mixed (e.g. patients write "2hindert11" instead of zweihundertelf (two hundred eleven)). Due to the frequent occurence of acalculia in dementia and its specific features, it is suggested that acalculia should be integrated into the criteria for dementia and that number processing and calculation tests are used in the diagnosis of dementia.

Aged↗

Prognostic relevance of quantitative topographical EEG in patients with poststroke aphasia.

In this prospective study we analyzed the prognostic value of topographical quantitative EEG (qEEG) in poststroke aphasia. Twenty-three right-handed patients (ages 56 +/- 12 years) with different types of aphasia were studied. Quantitative EEG under resting conditions and an aphasia test battery were applied twice, 2 and 8 weeks after a stroke. EEG power fast Fourier transform was performed for delta (2-3.5 Hz), theta (4-7.5 Hz), alpha (8-13 Hz), and beta (13.5-20 Hz) frequency bands. EEG abnormalities within and outside speech relevant areas are related to restitution of poststroke aphasia. In the ischemic regions they indicate local disturbances; outside they reflect failures in neuronal networks involved in the generation and propagation of the alpha rhythm.

Adult↗

[Language activation in ischemic stroke and brain tumor: a PET study].

Disturbance of neurologic function in disorders of the central nervous system is expressed as altered activation pattern in functional networks after specific tasks, and can be studied by functional imaging modalities, e.g. positron emission tomography (PET). Language, a complex brain function is based on the interplay of a distributed network in which partial functions are executed in various centers and tasks are hierarchically organized according to their complexity. The specialization of different centers and the lateralization of integrative functions into the dominant (usually left) hemisphere is achieved by collateral and transcallosal inhibition of structures of lower order in the network. Patients with ischemic stroke often suffer from aphasia; the features and the prognosis of this disturbance is determined by the localization and the extent of the infarct in the dominant hemisphere. The preservation of the left superior temporal gyrus or its functional reintegration, respectively, is of utmost importance for the recovery of the deficits and for a satisfactory outcome. Reactivation of this region in repeated PET-activation studies were related to a favorable outcome, activation of other eloquent regions or of contralateral areas were accompanied by some improvements, but never indicated recovery of sufficient speech production. Symptoms develop slowly in patients with tumors in the left hemisphere, and the functional network can adapt to the lesion. In these patients a dislocation of areas activated during language tasks was observed, either to ipsilateral regions usually not involved or to contralateral homotopic areas. Aphasia was frequent in cases with activation shift to the subdominant hemisphere, and the right over left asymmetry in activation of the cerebellum was correlated to the severity of language impairment. The shift of dominance in activation could be reversed after surgical resection of the tumor leading to improved speech performance. The patterns of intrahemispheric as well as interhemispheric compensation may be explained by reduction of collateral inhibition of specific centers on other structures within the network (disinhibition): circumscript and/or slowly developing lesions disinhibit surrounding areas leading to increases and to displacements of activated centers; large morphological defects reduce the transcallosal inhibition leading to the activation of contralateral regions.

Adult↗

Combinatorial synthesis of CCR5 antagonists.

Herein we report the preparation of a combinatorial library of compounds with potent CCR5 binding affinity. The library design was aided by SAR generated in a traditional medicinal chemistry effort. Compounds with novel combinations of subunits were discovered that have high binding affinity for the CCR5 receptor. A potent CCR5 antagonist from the library, compound 11 was found to have moderate anti-HIV-1 activity.

CCR5 Receptor Antagonists↗