PubMed Health⌕ Search

Biomedical subjects

G Vogler

Publications and source records attributed to G Vogler.

At least 19 recordsLinked to original sources

Exposure to inorganic arsenic metabolites during early human development.

Because of the lack of data on the exposure to and toxic effects of inorganic arsenic during early human development, the transfer of arsenic to the fetus and suckling infant was studied in a native Andean population, living in the village San Antonio de los Cobres in the North west of Argentina, where the drinking water contains about 200 micrograms/liter. The concentration of arsenic in cord blood (median, 9 micrograms/liter) was almost as high as in maternal blood (median, 11 micrograms/liter), and there was a significant correlation between the two. Thus, at least in late gestation, arsenic is easily transferred to the fetus. The median concentration of arsenic in the placenta was 34 micrograms/kg, compared with 7 micrograms/kg previously reported for nonexposed women. Interestingly, essentially all arsenic in the blood plasma of both the newborns and their mothers was in the form of dimethylarsinic acid (DMA), the end product of inorganic arsenic metabolism. Similarly, about 90% of the arsenic in the urine of both the newborns and mothers in late gestation was present as DMA, compared with about 70% in nonpregnant women (p < 0.001). This may indicate that methylation of arsenic is increased during pregnancy and that DMA is the major form of arsenic transferred to the fetus. The increased methylation in late gestation was associated with lower arsenic concentrations in blood and higher concentrations in urine, compared with a few months postpartum. The arsenic concentrations in the urine of the infants decreased from about 80 micrograms/liter during the first 2 days of life to less than 30 micrograms/liter at 4.4 months (p = 0.025). This could be explained by the low concentrations of arsenic in the breast milk, about 3 micrograms/kg.

Arsenic↗

Low-level arsenic excretion in breast milk of native Andean women exposed to high levels of arsenic in the drinking water.

OBJECTIVE: To investigate the excretion of arsenic in breast milk of lactating native Andean women living in a village in northwestern Argentina with high concentrations of arsenic in the drinking water (about 200 micrograms/l) and to assess the exposure of children to arsenic during the very first period of life. METHODS: The study included ten lactating women and two nursing babies. Hydride-generation atomic absorption spectrometry (HG-AAS) was used to determine the concentration of arsenic in samples of human milk, drinking water, blood, and urine. RESULTS: The concentrations of arsenic detected in maternal blood (total arsenic) and urine (metabolites of inorganic arsenic) were high, averaging 10 and 320 micrograms/l, respectively. In subjects without known exposure to arsenic the average concentrations found in blood and urine are 1-2 and about 10 micrograms/l, respectively. The metabolites of inorganic arsenic constituted more than 80% of the total arsenic in the urine, which shows that inorganic arsenic was the main form of arsenic ingested. The average concentration of arsenic detected in human milk was 2.3 micrograms/kg fresh weight (range 0.83-7.6 micrograms/kg). Although data on background levels of arsenic in human breast milk are scarce, the present concentrations seem to be slightly elevated. However, considering the high levels of arsenic exposure in the mothers, the total arsenic concentrations measured in human milk were low. In concordance with the low concentrations of arsenic found in the milk, the concentrations of arsenic metabolites measured in the urine of two of the nursing babies were low: 17 and 47 micrograms/l, respectively. CONCLUSIONS: The low concentrations of arsenic detected in the breast milk and urine of the two nursing babies in relation to the high level of maternal exposure to arsenic indicate that inorganic arsenic is not excreted in breast milk to any significant extent. This is a very important reason for long breast-feeding periods.

Adolescent↗

Glucocorticoid interactions with memory function in schizophrenia.

Glucocorticoid (GC) exposure can affect brain function, including potential adverse effects on hippocampal physiology and on specific elements of cognitive performance. In a prior study of healthy adult humans, decreased verbal memory performance was detected during four days of double-blind, placebo-controlled dexamethasone (DEX) treatment. Using an identical experimental design and sample size (n = 19), the cognitive effect of DEX treatment was studied in 11 subjects with schizophrenia, compared with 8 receiving placebo. In contrast to the effect in healthy adults, GC treatment with DEX at this dose (cumulative 3.5 mg) and duration did not decrease verbal memory performance or other measures of cognitive function in the patients with schizophrenia. When data from this experiment was compared with data from the previous study of healthy adults, covarying differences in baseline memory performance, a significant 3-way interaction was detected between subject group, treatment condition, and the repeated measurements of verbal memory performance across baseline, treatment and washout (F[3,87] = 4.84, p = .0066), suggesting differential cognitive effects of DEX in the patients versus the previously studied healthy subjects. Baseline plasma cortisol concentrations (0800 h) prior to DEX treatment were inversely correlated with baseline delayed (rs = -0.536, p = .03) verbal recall performance, supporting a previous report. The current results await replication using a larger sample size but provide preliminary evidence for an altered behavioral response to acute GC exposure in schizophrenic versus healthy subjects, and further evidence for a relationship between chronic changes in circulating cortisol and the memory impairments found in this disorder.

Adult↗

North American opossum Didelphis virginiana as a fetal nephrotoxicity model: histologic and ultrastructural assessment of uranyl nitrate (UN)-induced damage.

We have used our opossum model of fetal nephrotoxicity to investigate uranyl nitrate-induced morphologic changes in the developing kidney. The present study establishes a renal dose response curve for the uranyl nitrate (UN). We find that pups treated with nonlethal doses of UN do not demonstrate growth retardation compared to saline-treated controls. The kidneys of UN-treated pups are heavier than the control animals, an effect less apparent the longer the pups are followed. A low dose of 60 mg/kg of UN administered to small pups causes slight histologic derangement but nevertheless more change than the same dose administered to larger more mature pups. Using a dose of 100 mg/kg of UN that effectively causes nonfatal renal disruption, we examined the kidneys from 4 to 42 days following injection. We find that tubular dilation and epithelial necrosis starts soon after treatment (day 4) and reaches its maximum during the second and third week (11 and 22 days). Architectural restoration appears complete by the end of the third week. By electron microscopy, UN induces sequential structural damage with loss of proximal tubule brush border, epithelial necrosis with intact basement membranes and regeneration at 4, 11, and 22 days. Residual tubular mitochondrial damage is present at 42 days in spite of histologically normal tubules. No apparent lesions are seen in glomeruli. Fibroblastic interstitial proliferation in UN-treated kidneys at 11 days is not followed by appreciable fibrosis when assessed at 22 and 42 days. As the structural changes caused by 100 mg/ml UN administration in fetal opossum kidneys are reversible, this is a useful model to study the molecular mediators responsible for this form of renal damage and repair.

Animals↗

Right ventricular end-diastolic volume as a measure of preload.

Right ventricular (RV) end-diastolic volume index (RVEDVI) measured by a modified thermodilution pulmonary artery catheter has been proposed as an improved measure of cardiac preload, compared with pulmonary capillary wedge pressure (PCWP). This study compared the correlation of RVEDVI and PCWP with cardiac index (CI) to determine which parameter better reflected ventricular preload. Modified thermodilution catheters were placed in 38 critically ill patients. Hemodynamic parameters were recorded in these patients at 2- to 4-hour intervals for 1 to 7 days. Complete data sets (1,008) were obtained. Regression analysis was performed comparing PCWP, RVEDVI, RV ejection fraction (RVEF) to CI in the entire group and in individual patients. Because mathematical coupling may exist between RVEDVI and CI, the correlation between these variables was corrected for mathematical coupling using the method described by Stratton. Simple regression analysis of data from all patients, uncorrected for mathematical coupling, yielded a significant correlation between CI and RVEDVI (r = 0.60, p < 0.0001), RVEF (r = 0.37, p < 0.0001), and PCWP (r = 0.01, p < 0.001). Correction for mathematical coupling between RVEDVI and CI resulted in a minor changes of the correlation coefficient to 0.56. In individual patients, a significant, uncorrected correlation (p < 0.05) was found between RVEDVI and CI in 27 of the 38 patients, whereas 11 patients had a significant correlation between PCWP and CI. RVEDVI correlated more closely with CI than did PCWP, even after correlation for mathematical coupling. In both the group as a whole and in individual patients, RVEDVI was a better indicator of cardiac preload.

Adolescent↗

Insulin-like growth factor improves renal architecture of fetal kidneys with complete ureteral obstruction.

Others have previously demonstrated that the administration of insulin-like growth factor-I accelerates recovery from ischemic acute tubular necrosis in the rat kidney. We investigated the effect of insulin-like growth factor-I on the histology of unilaterally obstructed kidneys in the pouch young of the North American opossum, Didelphis virginiana. In this model complete unilateral ureteral obstruction reliably induces statistically significant degrees of caliceal dilatation, tubular cystic change, and cortical and medullary fibrosis in kidneys examined 1 week after the creation of complete obstruction. Cortical and medullary inflammation is also increased after 1 week of obstruction in this model but not to a degree that is statistically different than control (sham operated) animals. We administered insulin-like growth factor-I to opossum pups with complete unilateral obstruction created at a length of 5 cm. (age 25 days, human equivalent 18 to 20 weeks). Insulin-like growth factor-I (400 mcg/kg.) was injected subcutaneously on the day of operation and again on days 2 and 4 postoperatively. The animals were sacrificed 1 week after obstruction and the formalin fixed, paraffin embedded kidneys were assessed histologically. In the obstructed kidney insulin-like growth factor-I ameliorated the development of fibrosis (cortical and medullary) and caliceal dilatation such that these characteristics did not differ significantly from those of sham operated animals. Tubular cystic change in the obstructed kidneys was also decreased by insulin-like growth factor-I administration but not to significant levels. Insulin-like growth factor-I treatment in obstructed animals resulted in significantly more inflammation (cortical and medullary) than in the sham operated animals. We also administered insulin-like growth factor-I to normal pups with no other intervention. These insulin-like growth factor-I treated pups did not differ from sham pups for any characteristic studied. Our study suggests that there is protective effect of insulin-like growth factor-I on renal architecture when administered in the setting of experimental fetal ureteral obstruction.

Animals↗

Experimental ureteral obstruction in the fetal opossum: histologic assessment.

In the North American opossum, Didelphis virginiana unilateral complete ureteral obstruction (ECO) and partial unilateral (EPO) ureteral obstruction were created during the early metanephric stage of kidney development in pups attached to the teat (approximately 4.5 cm. long, 20 days old). At 70 days of pouch life (full-term equivalent in the human) some completely obstructed ureters were unobstructed with reanastomosis in the bladder (RECO). Other pups underwent unilateral complete ureteral ligation at this full-term equivalent (70 days of pouch life) and constituted the late obstruction (LCO) group. Unoperated animals constituted the control (C) group. All animals were harvested when full grown (.7 to 2.2 kg.), and paraffin sections of the kidneys were stained with hematoxylin and eosin and Masson's Trichrome. In each a semiquantitative assessment of 24 histologic features was made and a digital score assigned. All experimental groups except EPO demonstrated significant epithelial and mesenchymal alterations. The changes can be broadly categorized as those secondary to obstruction of urine flow (dilation and cystic changes), those affecting epithelial differentiation in both cortex and medulla and those affecting mesenchymal differentiation. The EPO group demonstrated significantly fewer glomerular generations than did control kidneys. For all other characteristics studied, the EPO group did not differ from control. The ECO group demonstrated significant changes when compared with control for most parameters studied. Medullary dysplasia was more prominent in kidneys obstructed early. Reanastomosis (RECO) at a full-term equivalent did ameliorate the changes of medullary dysplasia and cortical atrophy. More collecting duct hyperplasia, cortical and medullary aplasia were present in the LCO group compared with the ECO. The LCO group also had less primitive duct formation and less medullary dysplasia than the ECO group. Renal blastema, previously unreported in experimental obstruction, was present in 41% of experimental kidneys.

Animals↗

Correlates of length of stay in gynecologic oncology patients undergoing inpatient surgery.

Escalating economic constraints require identification of the determinants of length of stay (LOS), since optimizing these may facilitate cost-effective care. However, risk factors for increased LOS are poorly understood. In order to identify correlates of long LOS, we retrospectively reviewed the charts of 252 consecutive patients who underwent major inpatient surgery on the gynecologic oncology service at Barnes Hospital during 1990. Of these, 86 had benign disease and 38 were excluded for other reasons, leaving 128 for analysis. The recorded variables of age, race, medical history, measures of nutritional state, primary cancer, prior therapy, blood loss, operating time, and attending surgeon were subjected to regression analysis. In order to avoid reducing cell numbers to insignificant sizes, the linked factors of type of surgery and primary site were not analyzed simultaneously. A separate analysis was performed substituting type of procedure for primary site. The mean LOS was 12 days (range, 4-30). Five factors emerged as significant correlates of longer LOS: decreasing preoperative albumin level (P < 0.001) and hemoglobin level (0.029), increasing age (0.017), operative blood loss (0.039), and prior platinum-based chemotherapy (0.043). Presence of vulvar and fallopian tube primaries was associated with significantly shorter LOS (0.023 and 0.037). Together these factors accounted for 36% of total variance in LOS. Substituting procedure type for primary site accounted for 37% of total variance in LOS and showed that only bowel surgery (0.001) and preoperative intracavitary implant were significantly correlated with longer LOS. Factors not associated with LOS (P > 0.05) were race, attending physician, number of preoperative medications or medical conditions, body mass index, other radiotherapy, and other primary sites and procedures. Future studies should attempt to determine why elderly, nutritionally depleted women undergoing long or complicated procedures are at high risk for long LOS and should assess interventions designed to minimize LOS for this high-risk group.

Adolescent↗

Viability of the rectus abdominis muscle following internal mammary artery ligation.

The purpose of this study was to determine if the rectus abdominis muscle in the dog model could be used as a transposition flap based on its proximal blood supply following ligation of the internal mammary artery. In 11 dogs, the left internal mammary artery and vein were ligated at the fifth intercostal space. Both the left and right rectus abdominis muscles were elevated from their respective beds, dividing the inferior epigastric and intercostal vascular pedicles. Each muscle was then wrapped in a thin silicone sheet and replaced. One week later the dogs were returned to surgery and the muscles inspected. The right rectus abdominis muscle was completely viable in all the dogs. In 10 of the 11 dogs, the left rectus abdominis muscle was completely viable. We conclude that a superiorly based rectus abdominis muscle in the dog can maintain its viability following ligation of its proximal blood supply at the fifth intercostal space.

Abdominal Muscles↗

Experimental ureteral obstruction in the fetal opossum. I. Renal functional assessment.

The North American opossum Didelphis virginiana was used as a model for fetal urinary obstruction. In this animal the fetus develops on a teat in a pouch and, therefore, it is accessible to surgical intervention. Unilateral ureteral obstruction was created at a mid trimester developmental equivalent in 8 pups, late ureteral obstruction was created in a similar fashion in 6 pups at a full-term equivalent and unobstruction of 9 pups was accomplished with a ureteroneocystostomy at a full-term equivalent. After early intervention 6 pups were found to have only partial ureteral obstruction as measured by mild dilatation and probe patency of the ureter. The control group consisted of 11 unoperated animals. The animals were maintained until adulthood when they were harvested after obtaining creatinine clearances from both kidneys. All dilated urinary systems were cultured for bacteria and they were sterile.

Animals↗

Frequent fallers. Leading groups to identify psychological factors.

CNAs might be good leaders for groups of frequent fallers for several reasons, two of which are that they provide hands-on care and they know the residents well. Residents who fall frequently do not see themselves as persons who fall; they slip, trip, or slide. Single fallers explore ways to prevent another fall. Residents attempting to "do for themselves" and thus maintain their highly-prized independence is a factor contributing to falls. Preservation of autonomy and self-esteem are co-factors. Denial and independence in the faller need to be identified, supported as strengths, and incorporated into a resident's plan of care.

Accident Proneness↗

Induced renal dysplasia in the young pouch opossum.

Using the North American opossum, Didelphis virginiana, we have developed a new model for studying the effects of early fetal urinary obstruction on subsequent renal development. We have successfully induced renal dysplasia in the marsupial that has a typically mammalian kidney.

Animals↗

Protective barrier effect of the posterior lens capsule in exogenous bacterial endophthalmitis--an experimental primate study.

Ten eyes of five Rhesus monkeys underwent extracapsular lens extraction. The right eye of each monkey was allowed to retain an intact posterior capsule. The left eye of each monkey had a wide primary capsulectomy with minimal anterior vitrectomy. In order to exclude operative contamination, we waited 2 to 3 weeks later to challenge the eyes with bacteria. Seventy-two hours after anterior chamber injection of equal numbers of Staphylococcus aureus, diagnostic cultures were obtained from the anterior chamber and vitreous and correlated with the clinical findings. Injection of 10,000 S. aureus produced culture-positive endophthalmitis in eyes that had undergone posterior capsulectomy, but it failed to produce endophthalmitis in fellow eyes with intact posterior capsules. This suggest that a significant barrier effect against the development of bacterial endophthalmitis exists in the eyes with intact posterior capsules.

Animals↗

Protective barrier effect of the posterior lens capsule in exogenous bacterial endophthalmitis: an experimental pseudophakic primate study.

Five Rhesus monkeys underwent cataract extraction and intraocular lens implantation. The right eyes had extracapsular extraction, implantation of a Shearing J-loop posterior chamber lens, and primary posterior capsulotomy. The fellow eyes had extracapsular extraction, subtotal posterior capsulectomy, a limited anterior vitrectomy, and anterior chamber implantation of a modified J-loop Sinskey-style intraocular lens. One to two weeks postoperatively, we inoculated the anterior chamber of each eye with 10,000 Staphylococcus aureus organisms. After enucleating the eyes, we obtained anterior chamber and vitreous cultures and examined the gross pathologic specimen for vitreous clarity 72 hours after inoculation. Twenty percent of right eyes had infection of the vitreous cavity, whereas in the fellow eyes, 80% demonstrated vitreal infection by examination of the sectioned gross pathologic specimens. Sixty percent of the left eyes had positive vitreous cultures. These findings suggest that the posterior capsule acts as a barrier to prevent the spread of infection from the anterior chamber to the vitreous cavity in experimental, primate pseudophakia.

Animals↗