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Biomedical subjects

B Baldwin

Publications and source records attributed to B Baldwin.

At least 19 recordsLinked to original sources

Human AML cells in NOD/SCID mice: engraftment potential and gene expression.

Most cases of human acute myeloid leukemia (AML) engraft in irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Intravenous transfer of as few as 10(5) human AML cells resulted in engraftment. Cases with poor prognosis clinical features, including FLT3 mutations, tended to engraft efficiently. Nevertheless, AML cells obtained from patients at relapse did not engraft more efficiently than cells obtained from the same patients at initial diagnosis. One passage of human AML cells in NOD/SCID mice did not appear to select for increased virulence, as measured by serial transplantation efficiency. Finally, cDNA microarray analyses indicated that approximately 95% of genes were expressed at similar levels in human AML cells immunopurified after growth in mice, as compared to cells assessed directly from patients. Thus, the growth of human AML cells in NOD/SCID mice could yield large numbers of human AML cells for direct experimental use and could also function as a renewable, potentially unlimited source of leukemia cells, via serial transplantation.

Acute Disease↗

Correlates of disruptive behavior in severely cognitively impaired nursing home residents.

This article provides information about correlates of "disruptive behaviors" among nursing home residents with dementia. We used averages of multiple observations for a wide range of behaviors (n = 45) across 11 months to gather this information. We placed behaviors into four separate categories: physically aggressive, physically non-aggressive, vocally agitated, and vocally aggressive. Then, we tested associations between these categories and demographic, cognitive, and health variables. Cognitive status and selected demographic variables were associated with the behavior categories; adding health variables did not improve prediction. Lower cognitive status was associated with more disruptive behaviors. Our findings suggest that cognitive status, but not health variables, predicts disruptive behavior among nursing home residents with dementia.

Aged↗

Variation in prostate position quantitation and implications for three-dimensional conformal treatment planning.

PURPOSE: This study describes and quantitates the motion, i.e., variation in position, of the prostate within the pelvis and its effect on target and normal organ dose. METHODS AND MATERIALS: The motion of the planning target volume (PTV) borders and center of mass was studied in 13 patients with carcinoma of the prostate through the use of superimposed serial computerized tomography (CT) scans. Changes in bladder and rectal volumes were measured and their relationship to displacements of the PTV position were noted. The effects of this motion on target and normal organ doses were measured. RESULTS: A variability in the position of the PTV is seen over time, which is related to changes in bladder and rectal volumes. The one standard deviation displacements of the PTV center of mass with respect to the planning scan center of mass position were 0.12, 0.40, and 0.31 cm in the lateral, anterior-posterior, and superior-inferior directions, respectively. Movement was significantly larger in the superior part of the PTV above the base of the bladder than in the inferior part. Movement of the borders of the PTV outward from the patient axis; hence, toward the edges of the treatment field, was also examined. Outward displacements of the anterior target border below the base of the bladder were less than 0.3 cm in 90% of the cases, and 1.4 cm above the bladder base. For the posterior wall these displacements were less than 0.7 cm and 1.1 cm, respectively, whereas the lateral border displacements were less than 0.3 cm throughout (90% confidence limits). These displacements would cause a median of 6% of the PTV to receive less than 95% of the planned dose for any given treatment day in these patients; the effect on rectal and bladder wall doses was greater and true doses may not be measurable through the use of only one treatment planning CT scan. CONCLUSIONS: The prostate is not a static organ, but rather has some limited motion in the pelvis secondary to bladder and rectal volume changes. This motion has been quantified for a group of patients, and may provide a guide to further studies on the placement of field borders.

Humans↗

Long-term entrainment of circannual reproductive and metabolic cycles by Northern and Southern Hemisphere photoperiods in woodchucks (Marmota monax).

Woodchucks were exposed to simulated Northern Hemisphere (boreal) or Southern Hemisphere (austral) natural photoperiods in groups of 17 males and 17-18 females at 20-23 degrees C for 69 mo and examined monthly. Photoentrainment of endogenous cycles was evaluated based on dates of peak body weight, peak testis volume, increased serum testosterone in males, and increased serum progesterone in females. Boreal photoperiods entrained and synchronized annual cycles in 15 of 17 males and in all 17 females; 2 males never entrained and free-ran at 9- to 11-mo intervals. Austral photoperiods phase-advanced cycles by approximately 6 mo after 2.5 yr in 34 of 35 animals. Four entrained males became refractory after 4 yr, free-running at 6- to 10-mo intervals. Photoentrained boreal animals became phase-advanced by 1 mo during the first 2 yr, and then had 12-mo cycles for 4 yr. In Year 5, on average, boreal cycles included initial testosterone elevations in mid-January (vs. mid-July in australs), parturition in early March (vs. early September in australs), and peak body weight in mid-July (vs. late January in australs). The results confirm that endogenous circannual cycles of woodchucks can be entrained and synchronized for 6 yr by daily changes in photoperiod similar to those of midnorthern latitudes, and can be re-entrained and phase-advanced 6 mo by photoperiods of midsouthern latitudes.

Animals↗

Estrus, fertility, early embryo development, and autologous embryo transfer in laboratory woodchucks (Marmota monax).

Reproductive parameters were studied in female laboratory woodchucks over a 6-year period. The pregnancy rate in adult females after ad libitum exposure to a male (n = 643) was 72%; that after limited (4 to 8 h) exposure with video observations (n = 31) was only 37%. However, limited exposure resulted in a 75% ovulation rate, suggesting a problem with fertilization and not ovulation. The ovulation rate was 0% in the absence of mating (n = 10), suggesting that spontaneous ovulation is not the usual situation in this species. With ad libitum mating, fertility was greater (P < 0.05) for 2- to 4-year-old females (73%) than for 1-year-old (56%) or > or = 5-year-old (58%) females. Mean (+/-SEM) litter size at birth was greater (P < 0.05) for 2- to 5-year-old animals (4.0 +/- 0.1) than for 1-year-old animals (2.9 +/- 0.2). However, in 1-year-old females the neonatal mortality was low, and the litter size at weaning (2.4 +/- 0.3 pups) did not differ from that of older females (2.7 +/- 0.1 pups). The measurement of vulval diameter every 3 to 4 days in 31 adult females suggested that enlargement to > or = 7 mm was indicative of proestrus or estrus and was a good indicator of willingness to accept mounting by males. Vulval swelling > or = 7 mm (n = 31) lasted 5 to 47 days. Fertile mating occurred from 3 to 30 days after vulval diameter reached > or = 7 mm, near the time of peak enlargement (10.1 +/- 0.2 mm), and was followed in several days by a decrease in vulval size. Fifty-three females were allowed only limited (6 to 10 h) video-observed exposure to males, with (n = 26) or without (n = 27) another 12 to 24 h of unobserved exposure, and were examined surgically for ovulation and pregnancy at known times after mating. There were no consistent differences among nonovulating, ovulating nonfertile, and fertile females in the longest duration of mating (7.2 +/- 0.4 min) or in the number of matings lasting > or = 1 min (5.7 +/- 0.8). Compared with nonfertile females, fertile females experienced more matings > or = 3 min in duration (3.3 +/- 0.4 versus 1.8 +/- 0.2) and > or = 5 min in duration (2.9 +/- 0.4 versus 1.1 +/- 0.1). At postmating days 1, 2, 3, 4, 5, 6, and 7 the embryos were observed to be 1-, 4-, 4- to 32-cell morulae, 16- to 60-cell morulae, free-floating blastocysts, anti-measometrial peri-implantation blastocysts, and attached blastocysts respectively. Autologous transfer of day-5 uterine embryos of normal appearance into the noncontiguous contralateral uterine horn was performed in five females that had been subjected to a hemi-ovariectomy. Transfers resulted in pregnancy and litters in four of the five females. The results suggest that this large, circannual sciurid rodent can be successfully and predictably bred as a laboratory animal model, has vulval changes indicative of proestrus, is principally an induced ovulator, has an early embryo development rate similar to that of rats and mice, and may be amenable to reproductive technologies developed for more common laboratory rodents.

Animals↗

Comparing two strategies of cardiopulmonary bypass cooling on jugular venous oxygen saturation in neonates and infants.

BACKGROUND: Cerebral protection during deep hypothermic circulatory arrest is predicted on efficient and complete cerebral cooling. Institutions approach cooling quite differently. We compared two different cooling strategies in terms of measured jugular venous bulb saturations in 39 infants undergoing deep hypothermic cardiopulmonary bypass to evaluate the effect of institutional cooling practices on jugular venous bulb saturation, an indirect measure of cerebral cooling efficiency. METHODS: The patients were grouped based on the method of core cooling. In group A (n = 17), core cooling was achieved rapidly by setting the water bath temperature of the heat exchanger at 4 degrees to 5 degrees C, and the patient was cooled until rectal temperature and nasopharyngeal temperature were 15 degrees C or lower. In group B (n = 22), the heat exchanger was initially set at 18 degrees C and slowly lowered to 12 degrees C. Hypothermic temperatures of 12 degrees C were maintained until the nasopharyngeal temperature was 18 degrees C or less and the rectal temperature was 20 degrees C or lower. Once cooling was complete, blood samples were analyzed by cooximetry for determination of arterial oxygen saturation and jugular venous bulb saturation. RESULTS: In group A, the measured jugular venous bulb saturation was 98.0% +/- 0.9% and the oxygen saturation to jugular venous bulb saturation difference was 0.3% +/- 0.5%, measured at the time that institutional cooling objectives were achieved (total cooling time, 15.0 +/- 0.45 minutes). In group B, jugular venous bulb saturation was 86.2% +/- 12% and the oxygen saturation to jugular venous bulb saturation difference was 10.8% +/- 12.2%, measured at the time that institutional cooling objectives were achieved (total cooling time, 17.5 +/- 1.1 minutes (p < 0.01). CONCLUSIONS: Differences in cardiopulmonary bypass cooling techniques may alter the rate at which jugular bulb saturations rise. We believe this represents an indirect measure of the efficiency of brain cooling and therefore of cerebral protection.

Body Temperature↗

Neuropsychiatry and SPECT of an acute obsessive-compulsive syndrome patient.

BACKGROUND: A 71-year-old man with no previous psychiatric history presented with an acute onset of obsessive-compulsive disorder (OCD) symptoms associated with a right inferior parietal infarct. There were no abnormal neurological signs. There were no noteworthy abnormalities on neuropsychological testing. METHOD: Whereas a computerised tomography scan showed only a right inferior parietal infarct, a single photon emission computerised tomography (SPECT) scan revealed that in addition to the infarct there was decreased regional cerebral blood flow in the right basal ganglia and temporal areas. There was higher activity in the right orbitofrontal area than in the left. RESULTS: The patient improved with standard drug therapy and psychotherapy. CONCLUSIONS: SPECT is effective in the diagnosis of neuropsychiatric disorders such as OCD, and the pathological changes in brain metabolism detected by SPECT may be reversed by both drug therapy and psychotherapy.

Aged↗

[Pick and focal brain atrophy].

In 1892 Arnold Pick presented the case of an elderly demented patient with severe aphasia and global brain atrophy most accentuated at the left temporal lobe. Picks main interest was the relationship between focally accentuated brain degeneration and focally accentuated neuropsychological deficits, and this was what he wanted to demonstrate. He made no effort to describe a new form of dementia. The term "Pick's disease" which was introduced 30 years later implies the existence of a nosological entity with characteristic clinical features, localisation and histology. The neuropathological causes of focally accentuated brain atrophies are varied. Neocortical pyramidal cell loss with or without spongiform changes, cortical and subcortical gliosis have commonly been described. Achromatic neuronal ballooning ("Pick's cells") and intraneuronal argentophilic inclusion bodies ("Pick's bodies"), Alzheimer type plaques and tangles and other features were found in a smaller number of cases. Several authors confirmed an association between the localisation of brain atrophy and its clinical manifestations, but no convincing relationship has been demonstrated between the clinical symptoms and the underlying histology. In several studies frontal lobe degeneration was found in 10% to 20% of the demented patients, whereas aphasia, apraxia and other pronounced deficits in the context of focally accentuated brain atrophy were described less frequently. An early clinical distinction between atypical early stages of Alzheimer's disease and other forms of slowly progressive dementing disorders is virtually impossible in these cases. Prospective studies documenting the clinical and anatomical findings are needed to examine the reliability of these surmised brain-behaviour relationships in degenerative brain diseases more reliably. A descriptive approach offers a better basis for data collection than the premature diagnosis of a poorly defined disease like "Pick's".

Alzheimer Disease↗

Effect of altering pump flow rate on cerebral blood flow and metabolism in infants and children.

The effects of reduced pump flow rate (PFR) on cerebral blood flow, cerebral oxygen consumption (CMRO2), oxygen extraction, cerebral vascular resistance, and total body vascular resistance were examined in 27 pediatric patients during hypothermic cardiopulmonary bypass (hCPB). During steady state hCPB the extracorporeal flows were randomly adjusted to a conventional PFR and a reduced PFR for each patient. The reduced pump flow rates were dictated by surgical needs. Cerebral blood flow measured using Xenon 133 clearance, and CMRO2 and oxygen extraction were calculated. Our results demonstrated that cerebral blood flow and CMRO2 are unchanged if pump flow rates are reduced by 35% to 45% of conventional PFRs at moderate and deep hypothermic temperatures. Reductions in PFR of 45%-70% from conventional PFRs affect the brain differently during either moderate or deep hCPB. At moderate hCPB (26 degrees to 29 degrees C), reductions in PFRs of 45% to 70% resulted in a significant decrease in cerebral blood flow and CMRO2, whereas oxygen extraction increased in a compensatory manner. During deep hCPB (18 degrees to 22 degrees C), PFR reductions of 45% to 70% of conventional PFR significantly reduced cerebral blood flow and CMRO2 but did not increase oxygen extraction, suggesting that at deep hypothermic temperatures, cerebral blood flow and CMRO2 exceed cerebral metabolic needs. Cerebral vascular resistance increased significantly with decreasing temperature but was not affected by pump flow reductions. We have derived indices for minimal acceptable low-flow cardiopulmonary bypass based on the known effects of temperature on cerebral metabolism and have speculated on its utility based on our limited data and a literature review.

Adolescent↗

Detecting depression in elderly medically ill patients: the use of the Geriatric Depression Scale compared with medical and nursing observations.

In a study of 59 elderly medically ill in-patients, 35% were found to have significant depressive symptomatology, as detected by the Geriatric Mental Status Schedule (GMSS). Of two screening methods, the Geriatric Depression Scale (GDS) performed satisfactorily but detection by nurses was poor. Acknowledgement of depression in medical casenotes was low. Training of nurses might improve detection; otherwise a mood-rating scale such as the GDS should be incorporated into routine practice.

Aged↗

Alteration of growth, advancement of puberty, and season-appropriate circannual breeding during 28 months of photoperiod reversal in woodchucks (Marmota monax).

In woodchucks (Marmota monax), as in other marmotine rodents, endogenous circannual metabolic and reproductive cycles persist and free-run at intervals of 10-12 mo for up to 4 yr in a neutral photoperiod of 12L:12D. The annual metabolic cycle is not altered by exposure to constant long days or short days for several months. In the wild, changes in food intake cause body weight to peak in late summer and reach nadirs in early spring, and there is a single annual breeding season in late winter. To determine whether normal changes in photoperiod entrain the endogenous circannual cycle, aspects of reproduction, food intake, and body weight were studied for 28 mo in eight groups of woodchucks housed in light-controlled rooms. These included four groups of 7-10 males and four groups of 7-10 females exposed to automated and continuous daily changes in photoperiod. The imposed changes in photoperiod resembled native Northern Hemisphere (boreal) changes or Southern Hemisphere (austral) changes in photoperiod. The treatments started at the summer solstice shortly after capture as 2.5-mo-old juveniles or 14.5-mo-old yearling adults. In austral vs. boreal woodchucks, started as juveniles, annual increases in testosterone and testis descent at 5, 14, and 23 mo of study were advanced by 2, 5, and 6 mo, respectively. Annual increases in progesterone at 7, 16, and 25 mo of study were advanced by 4, 5, and 6 mo, respectively. The older woodchucks were significantly but less dramatically affected by austral photoperiod for the first 6 mo of study, and by 8-12 mo were advanced the same as the younger animals. At 16-17 and 26-27 mo of photoperiod reversal, 16 austral females had normal pregnancy rates (78%) and produced normal-sized litters (4.3 +/- 0.2) that were advanced by 5 and 6 mo, respectively, relative to those of boreal controls. Body weights in austral vs. boreal juveniles were reduced at 3-5 mo of study but not in older woodchucks. At 1 and then 2 yr of austral lighting, peaks in body weight were advanced by 4 and then 5 mo relative to boreal controls in young animals, and by 2 and then 5 mo in older animals. Between 1 and 2 yr of austral lighting in both age groups the nadirs in food intake (45 g per day) were about 16-25% of peak food intake 6-8 mo earlier, as in boreals, but advanced by 5-6 mo relative to boreals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Three-dimensional dosimetry for radioimmunotherapy treatment planning.

Absorbed-dose calculations for radioimmunotherapy are generally based on tracer imaging studies of the labeled antibody. Such calculations yield estimates of the average dose to normal and target tissues assuming idealized geometries for both the radioactivity source volume and the target volume. This work describes a methodology that integrates functional information obtained from SPECT or PET with anatomical information from CT or MRI. These imaging modalities are used to define the actual shape and position of the radioactivity source volume relative to the patient's anatomy. This information is then used to calculate the spatially varying absorbed dose, depicted in "colorwash" superimposed on the anatomical imaging study. By accounting for individual uptake characteristics of a particular tumor and/or normal tissue volume and superimposing resulting absorbed-dose distribution over patient anatomy, this approach provides a patient-specific assessment of the target-to-surrounding normal tissue absorbed-dose ratio. Such information is particularly important in a treatment planning approach to radioimmunotherapy, wherein a therapeutic administration of antibody is preceded by a tracer imaging study to assess therapeutic benefit.

Brain Neoplasms↗

Immunosuppression with cyclosporine during the incubation period of experimental woodchuck hepatitis virus infection increases the frequency of chronic infection in adult woodchucks.

The immunosuppressive agent cyclosporine was given to adult woodchucks during acute experimental infection with woodchuck hepatitis virus (WHV). All 17 woodchucks given WHV alone or with a vehicle resolved the infection (i.e., zero chronicity), but when cyclosporine was given throughout the incubation and acute phases of infection (0-12 or 14 weeks; n = 12), the rate of chronic infection increased to 92%. When cyclosporine was given only during the incubation period (0-4 weeks; n = 10) or only during the acute phase of infection (2-12 weeks; n = 9), the rates increased to 50% and 55%, respectively. However, when the drug was given after the acute phase (8-18 weeks; n = 9), the chronic infection rate (11%) did not differ from that in untreated and vehicle controls. Immune responses inhibited by cyclosporine are important in resolution of acute WHV infection and occur mainly during the first 8 weeks. Immunosuppression of these responses for even short intervals during incubation (e.g., 0-4 weeks) increases the risk of chronicity.

Animals↗

A comparison of outcomes using three different methods of breast reconstruction.

In a review of 325 postmastectomy breast reconstructions, the aesthetic quality of the result and the risk of unsuccessful outcome were compared for three techniques: tissue expansion (105 breasts), latissimus dorsi myocutaneous flap (47 breasts), and TRAM flap (173 breasts). The aesthetic successes achievable with the three methods were similar, and some excellent results were achieved with each of them. The failure rate after tissue expansion (21 percent) was significantly higher than those observed with the TRAM (3 percent) and latissimus (9 percent) flaps. Tissue expansion also was not as aesthetically successful as other techniques in obese patients. For immediate breast reconstruction, the TRAM flap was the most aesthetically successful technique. Although tissue expansion has advantages and may be the best choice for some patients, methods that used autogenous tissue provided more consistent success.

Abdominal Muscles↗

The human fibroblast receptor for gp86 of human cytomegalovirus is a phosphorylated glycoprotein.

A human embryonic lung (HEL) cell receptor for gp86 of human cytomegalovirus that functions in virus-cell fusion was further characterized. Anti-idiotype antibodies that mimic gp86 were used to immunoprecipitate the 92.5-kDa fibroblast membrane receptor for gp86, which was preincubated with various endoglycosidases. The receptor, which has a pI ranging from 5.3 to 5.6, appears to be a glycoprotein with primarily N-linked sugar residues, some of which have high concentrations of mannose and some of which are complex oligosaccharides. Western blots (immunoblots) of electrophoretically transferred receptor incubated with various biotinylated lectins confirmed the presence of sugar moieties, including N-acetylglucosamine, glucose or mannose, and galactose, but not fucose or N-acetylgalactosamine. This gp86 receptor from uninfected HEL cells also incorporated radiolabeled phosphate from orthophosphoric acid, indicating that it is a constitutively phosphorylated receptor.

Animals↗

Improving documentation of aggressive behavior in nursing home residents.

1. Although 66% of the 1.3 million elderly nursing home residents in the US exhibit aggressive tendencies, research indicates that caregivers underdocument aggressive incidents. As a result, the extent of aggression is unknown. 2. This study found that LPNs reported the largest percentage (41%) of the 51 documented aggressive incidents, which reportedly occurred most frequently in the bathroom (49% of the time) between 5 AM and noon (86% of the time). Most aggressive residents (55.1%) never had visitors. 3. This study concludes that nursing practice would benefit from a consistent definition of aggression, an easy-to-use clinical instrument to collect data on aggression, and caregiver education programs on assessing aggression.

Aged↗