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Biomedical subjects

K M Kramer

Publications and source records attributed to K M Kramer.

At least 19 recordsLinked to original sources

The lower esophageal sphincter strength in patients with gastroesophageal reflux before and after laparoscopic Nissen fundoplication.

Lower esophageal sphincter pressure (LESP) and sphincter strength (LESS) were measured before and after short and floppy laparoscopic Nissen fundoplication (LNF) in 38 patients with severe gastro-esophageal reflux disease (GERD). These patients were compared with a control group of 23 healthy volunteers. GERD was assessed by stationary manometry, 24-h pH recordings and endoscopy. LESS was verified by motorized pull-back of an air-filled balloon catheter from the stomach into the esophagus. The catheter assembly was well tolerated by all study participants. LESP increased significantly after operation from 8 mmHg to 14 mmHg (75% of normal values; P < 0.0001), but compared to the control group, LESP (22 mmHg) decreased significantly (P < 0.002). In the control group and in patients with GERD, LESP and LESS showed excellent correlation (r = 0.97, r = 0.94, respectively). After LNF, LESS increased significantly from 0.6 to 1.6 N (P < 0.0001), about 166%. We conclude that the measurement of LESS is able to explain the discrepancy between satisfactory NF operation and the distinct increase of postoperative LESP. The evaluation of LESS is a helpful tool in assessing functional understanding of laparoscopic Nissen fundoplication with a short and floppy wrap.

Adult↗

Parental regulation of central patterns of estrogen receptor alpha.

Reduced levels of estrogen receptor alpha (ERalpha) in the medial amygdala (MeA) and bed nucleus of stria terminalis (BST) have been hypothesized to play a significant role in the expression of male behaviors associated with monogamy. Therefore, the regulation of ERalpha could be a critical factor in determining male behavior and the evolution of monogamy. Central expression of ERalpha immunoreactivity was compared in hybrid offspring from crosses between two phenotypically distinct populations of prairie voles (Microtus ochrogaster). Illinois voles (IL) are socially monogamous and display low levels of ERalpha, while Kansas voles (KN) display some characteristics associated with polygyny and have higher levels of ERalpha. In offspring from hybrid crosses, the pattern of ERalpha expression was dependent upon parentage; the two types of hybrid crosses did not produce the same ERalpha pattern in the offspring. In the BST and MeA, hybrid males expressed ERalpha patterns consistent with those of males from their mother's population, while hybrid females had ERalpha patterns typical of females belonging to their father's population. The parental-specific patterns of ERalpha expression are suggestive of genomic imprinting, therefore, the vole ERalpha (Esr1) gene was cloned and sequenced, and examined for allele-specific expression. Results from this study indicate that while maternal factors may play a major role the expression of ERalpha in their male offspring, genomic imprinting is unlikely to be involved, suggesting another mechanism is responsible.

Amygdala↗

Neonatal manipulations of oxytocin alter expression of oxytocin and vasopressin immunoreactive cells in the paraventricular nucleus of the hypothalamus in a gender-specific manner.

Early postnatal manipulations of oxytocin have long-term behavioral and physiological consequences; the present study examined the hypothesis that oxytocin or its absence influences the subsequent expression of either oxytocin or arginine vasopressin in the CNS. On postnatal day 1 female and male prairie voles (Microtus ochrogaster) received a single i.p. injection of oxytocin (3 microg), oxytocin antagonist (0.3 microg), or 50 microl of isotonic saline or were only handled. On postnatal days 1, 8 and 21, brains were fixed, sectioned and stained for oxytocin or vasopressin immunoreactivity and analyzed as a function of age, treatment and sex. Both oxytocin and vasopressin immunoreactivity were observed on day 1 in the supraoptic and paraventricular nuclei (PVN) of the hypothalamus. Numbers of oxytocin and vasopressin neurons increased with age in both nuclei. Females treated on postnatal day 1 with oxytocin or oxytocin antagonist displayed a significant increase in oxytocin immunoreactivity on day 21 in the PVN. In contrast, males treated with antagonist tended to have decreased vasopressin immunoreactivity in the same region. These results revealed that the effects of neonatal manipulation of oxytocin are age-dependent, site-specific and sexually dimorphic. The long-lasting effects of neonatal exposure to exogenous oxytocin and oxytocin antagonist indicate a role for oxytocin in the development of the CNS during the neonatal period, affecting the development of the oxytocinergic system in females and the vasopressinergic system in males. The developmental effects observed suggest one possible mechanism by which neonatal exposure to oxytocin or neonatal inhibition of endogenous oxytocin produces long-lasting behavioral and physiological alterations and could play a role in the development of male- and female-typical behavior.

Animals↗

Measurement of G(E(p))/G(M(p)) in e(-->)p---> e(-->)p to Q(2) = 5.6 GeV(2).

The ratio of the electric and magnetic form factors of the proton G(E(p))/G(M(p)), which is an image of its charge and magnetization distributions, was measured at the Thomas Jefferson National Accelerator Facility (JLab) using the recoil polarization technique. The ratio of the form factors is directly proportional to the ratio of the transverse to longitudinal components of the polarization of the recoil proton in the elastic e(-->)p---> e(-->)p reaction. The new data presented span the range 3.5< Q(2)< 5.6 GeV(2) and are well described by a linear Q(2) fit. Also, the ratio sqrt[Q(2)] F(2(p))/F(1(p)) reaches a constant value above Q(2) = 2 GeV(2).

Journal Article↗

Episodes of care: an overview of legal and regulatory issues.

The use of managed care, with its chief goal of delivering cost-efficient health coverage, predominates the American health benefit arena. Though the advent of managed care unquestionably has saved billions of dollars since the late 1980s, patients raised on a diet of unfettered treatment have seen choices decrease and care diminish. "Episodes of care," in which teams of professionals contract to provide an entirety of health care services involved with a given procedure in exchange for a fixed, global fee, allows for broader choices for patients at competitive costs for insurers.

Antitrust Laws↗

Trace element homeostasis during continuous sedation with propofol containing EDTA versus other sedatives in critically ill patients.

OBJECTIVE: To evaluate changes in serum and urinary zinc, cobalt, copper, iron, and calcium concentrations in critically ill patients receiving propofol containing disodium edetate (disodium ethylenediaminetetraacetic acid [EDTA]) versus sedative agents without EDTA. DESIGN: This was a randomised, open-label, parallel-group study with randomisation stratified by baseline Acute Physiology and Chronic Health Evaluation (APACHE II) scores. SETTING: Intensive care units (ICU) in 23 medical centres. PATIENTS: Medical, surgical, or trauma ICU patients 17 years of age or older who required mechanical ventilator support and sedation. INTERVENTIONS: A total of 106 patients received propofol containing 0.005 % EDTA (propofol EDTA), and 104 received other sedative agents without EDTA (non-EDTA). Only the first 108 patients were assessed for urinary trace metal excretion. Twenty-four-hour urine samples were collected on days 2, 3, and 7 and every 7 days thereafter for determination of zinc, cobalt, copper, iron, and calcium excretion; EDTA levels; urine osmolality; albumin levels; and glucose levels. The first 143 patients were assessed for serum concentration of zinc, cobalt, copper, iron, and calcium; creatinine; blood urea nitrogen; and albumin at baseline and once during each 24-hour urine collection. MEASUREMENTS AND RESULTS: For the assessment of trace metals, patients receiving propofol EDTA demonstrated increased mean urinary excretion of zinc, copper, and iron compared with the normal range. All patients receiving sedatives demonstrated increased urinary excretion of zinc and copper above normal reference values. Compared with the non-EDTA sedative group, the propofol EDTA group demonstrated increased urinary excretion of zinc and iron. Mean serum concentrations of zinc and total calcium were decreased in both patient groups. Serum zinc concentrations increased from baseline to day 3 in the non-EDTA sedative group but not in the propofol EDTA group. Renal function, measured by blood urea nitrogen, serum creatinine, and creatinine clearance, did not deteriorate during ICU sedation with either regimen. CONCLUSION: This study showed that critical illness is associated with increased urinary losses of zinc, copper, and iron. Propofol EDTA-treated patients had greater urinary losses of zinc and iron and lower serum zinc concentrations compared with the non-EDTA sedative group. No adverse events indicative of trace metal deficiency were observed in either group. The clinical significance of trace metal losses during critical illness is unclear and requires further study.

APACHE↗

A Bub2p-dependent spindle checkpoint pathway regulates the Dbf2p kinase in budding yeast.

Exit from mitosis in all eukaroytes requires inactivation of the mitotic kinase. This occurs principally by ubiquitin-mediated proteolysis of the cyclin subunit controlled by the anaphase-promoting complex (APC). However, an abnormal spindle and/or unattached kinetochores activates a conserved spindle checkpoint that blocks APC function. This leads to high mitotic kinase activity and prevents mitotic exit. DBF2 belongs to a group of budding yeast cell cycle genes that when mutated prevent cyclin degradation and block exit from mitosis. DBF2 encodes a protein kinase which is cell cycle regulated, peaking in metaphase-anaphase B/telophase, but its function remains unknown. Here, we show the Dbf2p kinase activity to be a target of the spindle checkpoint. It is controlled specifically by Bub2p, one of the checkpoint components that is conserved in fission yeast and higher eukaroytic cells. Significantly, in budding yeast, Bub2p shows few genetic or biochemical interactions with other members of the spindle checkpoint. Our data now point to the protein kinase Mps1p triggering a new parallel branch of the spindle checkpoint in which Bub2p blocks Dbf2p function.

Anaphase↗

Prophylactic antibiotics for severe acute pancreatitis: the beginning of an era.

Death from acute severe pancreatitis results from infection and multiple organ system failure occurring late in the course of illness. Patients with necrotizing pancreatitis involving at least one-third of the organ are at highest risk of secondary infection and death. We conducted a MEDLINE search to identify human trials of prophylactic antibiotics in acute pancreatitis. Results of early studies of prophylactic ampicillin to avoid secondary infection and death were negative, but the studies included patients with mild disease who are at low risk for infection. Antibiotics were beneficial in four recently completed studies: imipenem significantly reduced pancreatic and nonpancreatic sepsis (p< or =0.01); cefuroxime reduced all infectious complications (p<0.01) and deaths (p=0.0284); a regimen of ceftazidime, amikacin, and metronidazole reduced all infectious complications (p<0.03); and protocol use of imipenem significantly reduced pancreatic infection compared with nonprotocol antibiotics (p=0.04) and no antibiotics (p<0.001). Based on these results, we suggest early antibiotic prophylaxis in patients with necrotizing pancreatitis, but the best drug and duration of therapy are unknown.

Acute Disease↗

Budding yeast RSI1/APC2, a novel gene necessary for initiation of anaphase, encodes an APC subunit.

SIC1 is a non-essential gene encoding a CDK inhibitor of Cdc28-Clb kinase activity. Sic1p is involved in both mitotic exit and the timing of DNA synthesis. To identify other genes involved in controlling Clb-kinase activity, we have undertaken a genetic screen for mutations which render SIC1 essential. Here we describe a gene we have identified by this means, RSI1/APC2. Temperature-sensitive rsi1/apc2 mutants arrest in metaphase and are unable to degrade Clb2p, suggesting that Rsi1p/Apc2p is associated with the anaphase promoting complex (APC). This is an E3 ubiquitin-ligase that controls anaphase initiation through degradation of Pds1p and mitotic exit via degradation of Clb cyclins. Indeed, the anaphase block in rsi1/apc2 temperature-sensitive mutants is overcome by removal of PDS1, consistent with Rsi1p/Apc2p being part of the APC. In addition, like our rsi1/apc2 mutations, cdc23-1, encoding a known APC subunit, is also lethal with sic1Delta. Thus SIC1 clearly becomes essential when APC function is compromised. Finally, we find that Rsi1p/Apc2p co-immunoprecipitates with Cdc23p. Taken together, our results suggest that RSI1/APC2 is a subunit of APC.

Amino Acid Sequence↗

Criteria used to judge obese persons in the workplace.

Researchers have speculated that employers are less likely to hire obese persons for more publicly visible jobs, although this hypothesis remains untested. In the present study, 54 undergraduate students rated 40 jobs on several items, including the likelihood they would hire an obese person for each job. Multidimensional scaling showed a one-dimensional solution, labeled as physical activity, with participants less likely to hire obese persons for more active jobs. For hiring likelihood ratings for jobs at either end of the dimension appear to be most similar for men and individuals with more positive attitudes toward obese persons versus women and individuals with more negative attitudes toward obese persons. Implications for both theory and practice are discussed.

Adult↗

Posttraumatic syringomyelia: a review of 21 cases.

A retrospective study was conducted on 21 consecutive patients with combined clinical and radiologic evidence of posttraumatic syringomyelia. Medical records and radiologic studies were reviewed to determine the following: age at injury, mechanism of trauma, spinal column injury and resultant neurologic deficit, latency period between injury and clinical manifestations of posttraumatic syringomyelia, clinicoradiologic findings of posttraumatic syringomyelia, and results of treatment. The patients were found uniformly to have sustained significant trauma (gunshot wounds, falls, or vehicular accidents) with marked neurologic dysfunction at the time of injury. Latent periods ranged from 1 month to 23 years. The most commonly presenting symptoms were radicular pain, spasticity, sensory loss, hyperhidrosis, and weakness. The most common physical findings were spasticity, hypesthesia, and weakness. Long term followup was obtained in 17 (81%) of the cases and suggested a higher rate of satisfaction among patients treated with surgical decompression of the syrinx. Radicular pain and sensory disturbance responded most predictably to surgical intervention, whereas spasticity responded least favorably. It is concluded that posttraumatic syringomyelia is a potentially disabling but treatable late complication of spinal injury, warranting a high index of suspicion among physicians who observe patients with such trauma.

Adolescent↗

Two different types of double-strand breaks in Saccharomyces cerevisiae are repaired by similar RAD52-independent, nonhomologous recombination events.

In haploid rad52 Saccharomyces cerevisiae strains unable to undergo homologous recombination, a chromosomal double-strand break (DSB) can be repaired by imprecise rejoining of the broken chromosome ends. We have used two different strategies to generate broken chromosomes: (i) a site-specific DSB generated at the MAT locus by HO endonuclease cutting or (ii) a random DSB generated by mechanical rupture during mitotic segregation of a conditionally dicentric chromosome. Broken chromosomes were repaired by deletions that were highly variable in size, all of which removed more sequences than was required either to prevent subsequent HO cleavage or to eliminate a functional centromere, respectively. The junction of the deletions frequently occurred where complementary strands from the flanking DNA could anneal to form 1 to 5 bp, although 12% (4 of 34) of the events appear to have occurred by blunt-end ligation. These types of deletions are very similar to the junctions observed in the repair of DSBs by mammalian cells (D. B. Roth and J. H. Wilson, Mol. Cell. Biol. 6:4295-4304, 1986). When a high level of HO endonuclease, expressed in all phases of the cell cycle, was used to create DSBs, we also recovered a large class of very small (2- or 3-bp) insertions in the HO cleavage site. These insertions appear to represent still another mechanism of DSB repair, apparently by annealing and filling in the overhanging 3' ends of the cleavage site. These types of events have also been well documented for vertebrate cells.

Base Sequence↗

New telomeres in yeast are initiated with a highly selected subset of TG1-3 repeats.

The creation of new telomeres was studied by generating a site-specific double-strand break in diploid strains of Saccharomyces cerevisiae that are unable to carry out homologous recombination. New telomere formation occurred approximately 1% of the time but only when (T2G4)13 was present proximal to the break site. About half of the healing events occurred at a number of 1- to 9-bp G or G, T sequences located as far as 128 bp distal to the T2G4 repeats. Surprisingly, in 16 events at sites ending in GTGG, the first TG1-3 nucleotides added always included either an 11- or a 13-bp sequence (GTGTGGGTGTG or GTGTGTGGGTGTG), after which each new telomere diverged into a less ordered TG1-3 pattern. Moreover, at 75% of the remaining addition sites, these same 11- or 13-bp sequences were found overlapping the junction between the chromosomal primer and the newly added sequences. We propose that short G, T sequences near an organizing sequence such as (T2G4)13 can act as primers to pair with the template RNA of a telomerase and add new sequences that are complementary to that RNA.

Base Sequence↗

A 16-channel 8-parameter waveform electrotactile stimulation system.

We have developed a general-purpose electrotactile (electrocutaneous) stimulation system as a research tool for studying psychophysiological performance associated with various stimulation waveforms. An experimenter-defined command file specifies the stimulation current and waveform of each of the 16 channels. The system provides burst onset delay of 0-20 ms, phase current of 0-50 mA, interphase interval of 0-1000 microseconds, number of pulses per burst from 1-100, pulse repetition rate of 0.1-25 kHz, phase width of 2-1000 microseconds, and functionally-monophasic pulses (with zero dc current) or balanced-biphasic pulses (with equal positive and negative phases). The system automatically delivers the desired stimulation, prompts the subject for responses, and then logs subject responses. Key features of the system are 1) very flexible choice of bursts of pulsatile waveforms, 2) real-time control of all of the waveform parameters as mathematical functions of external analog inputs, and 3) high-performance electrode-driver circuitry.

Electric Stimulation↗