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R Reimer

Publications and source records attributed to R Reimer.

30 records · Page 2Linked to original sources

Cyclic adenosine monophosphate is the second messenger of prostaglandin E2- and vasoactive intestinal polypeptide-stimulated active bicarbonate secretion by guinea-pig duodenum.

In a guinea-pig model we determined the intracellular events mediating the response of duodenal epithelial cells to vasoactive intestinal polypeptide (VIP) and prostaglandin (PG) E2. Intravenous administration of VIP (10(-9) to 10(-7) mol/kg) and PGE2 (10(-9) to 10(-6) mol/kg) dose-dependently increased duodenal epithelial bicarbonate secretion against an HCO3- concentration gradient, measured by a luminal perfusion technique, in anaesthetized guinea-pigs up to 4.5-fold. This secretion could be mimicked by intraduodenal dibutyryl cyclic adenosine monophosphate (dBcAMP; 10(-9) to 10(-7) mol/kg). Secretin (10(-9) mol/kg) and PGF 2 alpha (10(-9) to 10(-7) mol/kg), both given intravenously, were without effect or considerably less efficient. For VIP and PGE2, specific receptors coupled to adenylate cyclase could be demonstrated in homogenates of isolated duodenal epithelial cells. VIP and PGE2 stimulated adenylate cyclase activity up to sixfold, whereas PGF2 alpha and secretin were considerably less potent and efficient. VIP and PGE2 increased intracellular cyclic AMP levels up to fivefold and ninefold, respectively. This was followed by an increase in cytosolic protein kinase A activity. Bicarbonate secretion was maximal at 30 min. Examination of the subcellular distribution of protein kinase A showed a predominant cytosolic location. These data support the notion the PGE2 and VIP cause bicarbonate secretion by the serial activation of adenylate cyclase and protein kinase A in duodenal epithelial cells.

Adenylyl Cyclases↗

Surgical treatment of spontaneous intracranial hypotension associated with a spinal arachnoid diverticulum. Case report.

The authors present the case of a 22-year-old woman who developed spontaneous intracranial hypotension as a result of a cerebrospinal fluid leak from a thoracic extradural arachnoid diverticulum. The patient was successfully treated by ligation of the diverticulum. The entity of spontaneous intracranial hypotension and its relevance to neurosurgery are discussed.

Adult↗

Laparoscopic placement of ventriculoperitoneal shunts: preliminary report.

We used a laparoscopic technique for the percutaneous placement of the peritoneal end of cerebrospinal fluid shunts in adult patients with obstructive or normal-pressure hydrocephalus. Concurrent with the initial cranial part of the procedure, pneumoperitoneum is established in a routine fashion, and a video-laparoscope and grasping forceps are inserted into the peritoneal cavity. With use of a pacemaker introducer kit, the peritoneal catheter is placed percutaneously under direct laparoscopic vision through a small upper abdominal incision into the peritoneal cavity. At the completion of the procedure, the patency of the assembled shunt system can be verified by observing free flow of cerebrospinal fluid from the catheter tip as the valve is being pumped. We found that this technique is particularly useful in technically challenging cases--for example, those involving obese patients and those who have undergone multiple abdominal operations. No complications associated with the technique were encountered.

Adult↗

Cholinergic regulation of guinea pig duodenal bicarbonate secretion.

Although it is well known that vagal stimulation induces duodenal HCO3- secretion, there is presently no information about the nature of the cholinoceptor and the intracellular signals involved. In a series of experiments performed in a guinea pig duodenal loop model in situ, intravenous carbachol, atropine, pirenzepine, and hexamethonium were used to determine the extent of cholinergic stimulation and the types of cholinoceptors. Carbachol (2 micrograms.kg-1.5 min-1) stimulated HCO3- secretion threefold, and atropine (0.1 mg.kg-1.5 min-1) and pirenzepine (1 mg.kg-1.5 min-1) both abolished this effect. In addition, hexamethonium (0.3 mg.kg-1.5 min-1) inhibited carbachol-stimulated duodenal HCO3- secretion. Vasoactive intestinal peptide (VIP, 5 micrograms.kg-1.5 min-1) stimulated duodenal HCO3- secretion, and this action was partly inhibited by atropine (0.1 mg.kg-1.5 min-1) but not by pirenzepine (1 mg.kg-1.5 min-1). [4Cl-D-Phe6,Leu17]VIP (3.3 mg/kg), an antagonist to VIP, reduced basal, VIP-stimulated, and carbachol-stimulated HCO3- secretion. To examine the role of Ca2+ in this process, Ca2+ ionophore A23187, verapamil, and nifedipine were employed. A23187 (5, 50, 500 micrograms.kg-1.5 min-1) stimulated duodenal HCO3- secretion, an effect blocked by the VIP antagonist, and modestly augmented the effect of carbachol. Verapamil (0.2 mg.kg-1.5 min-1) and nifedipine (1.7 mg.kg-1.5 min-1) stopped the effect of carbachol on duodenal HCO3- secretion. These results suggest, that in cholinergic regulation of duodenal HCO3- secretion, the M-cholinoceptor pathway, Ca2+, and VIP are involved.

Animals↗

Effects of EP-receptor subtype specific agonists and other prostanoids on adenylate cyclase activity of duodenal epithelial cells.

Rank order of agonist potency for activation of adenylate cyclase by the naturally occurring prostanoids PGE2, PGF2 alpha, PGD2, the stable PGI2 analogue iloprost, and the TXA2 mimetic U 46619, provides evidence for the existence of a distinct PGE-receptor on guinea-pig duodenal enterocytes. The PGE-receptor is likely to be of the EP2-subtype since the specific EP2-agonist 11-deoxy-PGE1 stimulated adenylate cyclase activity with a 20-fold higher potency than the EP1-agonist 17-phenyltrinor-PGE2 and the EP3-agonists MB 28767 and GR 63799. In addition, sulprostone (acting on both EP1- and EP3-receptors) was ineffective. Since the specific EP1-antagonist SC 19220 did not inhibit PGE2-stimulated adenylate cyclase activity, the involvement of EP1-receptors could be further excluded. The synthetic prostaglandin E-analogues misoprostol and nocloprost stimulated adenylate cyclase almost identically, though they were about 10-fold less potent than the natural PGE2.

Adenylyl Cyclases↗

[The effect of postural changes on cerebral hemodynamics during general anesthesia].

Anesthesia may compromise the regulation of systemic and cerebral hemodynamics following changes in body position. Sudden decreases in cerebral perfusion pressure due to changes from a horizontal to a head-elevated position may cause decreases in cerebral blood flow (CBF), particularly in patients with preexisting cerebrovascular disease. Transcranial Doppler sonography (TCD) permits on-line measurement of blood flow velocity (BFV) in human basal cerebral arteries, and there is evidence that monitoring of BFV may indicate relative changes in CBF. The present study compares the effects of changes from a horizontal to a head-elevated position on blood flow velocity in the middle cerebral artery (MCA) in 30 patients (ASA I) with different levels of steady state anesthesia (group A: n = 20, isoflurane = 1.0 vol% end-tidal; group B: n = 10, isoflurane = 0.4 vol% end-tidal; O2/N2O; FiO2: 0.3; 6 1/min). The MCA was insonated by transtemporal approach using a 2 MHz Doppler ultrasound system (TC2-64 B, EME) with a range-gating mechanism, adjustable sample volume depth, and flow direction discrimination. Systolic (Vsyst, cm/s) and mean flow velocity (Vmean, cm/s), pulsatility index (PI), mean arterial blood pressure (MAP, mmHg), heart rate (HR, b/min) and end-tidal CO2 (pet-CO2, mmHg) were recorded with the subjects lying flat (baseline values) and for 5 min following adjustment to a 35-40 degrees head-elevated position. There was a significant reduction of 25% for Vsyst from 79 +/- 17 cm/s (baseline) to 59 +/- 13 cm/s and a 33% decrease for Vmean from 52 +/- 9 cm/s (baseline) to 35 +/- 9 cm/s in group A immediately after repositioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Astrocytomas of the spinal cord in children and adolescents.

The authors review 32 cases of spinal cord astrocytoma in patients under 20 years of age who were treated at the Mayo Clinic between 1955 and 1980. There was a 1.3:1 male to female ratio. Twenty patients were between 6 and 15 years of age at the time of diagnosis. The duration of symptoms prior to definitive diagnosis varied from 5 days to 9 years, with an average of 24 months. The most common symptoms were pain (62.5%), gait disturbance (43.7%), numbness (18.8%), and sphincteric dysfunction (18.8%). The most common neurological findings were a Babinski response (50.0%), posterior column sensory dysfunction (40.6%), and paraparesis (37.5%). A median follow-up period of 8.6 years (range 0.8 to 25.5 years) revealed that the survival time diminished with increased histological grade of the astrocytoma (p less than 0.001). The development of postlaminectomy spinal deformities represented a serious postoperative complication. This occurred in 13 patients and was first recognized between 8 and 90 months postoperatively. Six deformities occurred following cervical laminectomy, and eight patients required at least one orthopedic procedure. It is crucial to follow these patients for an extended period of time to watch for postoperative spinal deformities.

Adolescent↗

Interaction specificity of the anthracyclines with deoxyribonucleic acid.

The interaction specificity of salmon sperm DNA with various derivatives of daunorubicin has been studied. The results of binding, viscometric, 1H nuclear magnetic resonance (NMR), flow dichroism, DNA template inhibition, rates of dissociation, and circular dichroism studies are found to be consistent with an intercalation mode of binding of the anthracycline ring as has been shown by other investigators. Moreover, it is observed that (i) strength of binding, (ii) the ease of dissociation of DNA-anthracycline complexes, and (iii) the degree of inhibition of the DNA-dependent RNA polymerase are dependent on the presence of the amino sugar moiety of daunoseamine. The results are consistent with specific H bonding of the amino group of the sugar moiety with DNA as has been suggested earlier by Pigram et al. (Pigram, W.J., Fuller, W., and Hamilton, L.D. (1972), Nature (London), New Biol. 235, 17). Peptide derivatives substituted at the amino sugar function of daunorubicin lower the affinity of the drug to DNA and presumably interfere with the "full insertion" of the anthracycline drugs between base pairs of DNA. The significance of these findings in relation to the biological efficacy of daunorubicin and related derivatives as antileukemic agents is discussed.

Animals↗

Sturcture-activity relationship of daunorubicin and its peptide derivatives.

The synthesis of potentially specific antitumor peptide derivatives of daunorubicin is presented. The interaction specificites of the drugs with nucleic acids have been examined via stop-flow kinetics as well as the inhibition of DNA template activity. It is found that the biological activity of the daunorubicin derivatives against the mouse P388 tumor is directly proportional to RNA polymerase inhibition and inversely proportional to the rate of dissociation of the DNA complex. It is concluded that the biological efficacy of drugs which act at the replicative and transcriptional level may be estimated by the more rapid in vitro techniques provided that problems of permeability, solubility, stability, etc., in vivo are not encountered.

Animals↗

Influence of estrogen receptor status on response to combination chemotherapy for recurrent breast cancer.

To determine the influence of cytoplasmic estrogen receptor (ER) status on response to chemotherapy among patients with recurrent breast cancer amenable to biopsy, we studied 65 patients who had ER determinations performed on metastatic lesions. The response to combination chemotherapy and duration of survival were determined in 49 of these patients who receive cytotoxic chemotherapy as their sole modality of treatment. Compared to patients with ER levels less than 3 femtomols/mg, patients with an ER concentration greater than or equal to femtomols/mg had a higher response rate (57% vs 21%, P less than 0.05) and a longer survival (35 vs 13 patients was attributable to response to subsequent hormonal manipulations. These differences between ER-positive and ER-negative patients were lessened by redefining ER-positive as greater than 10 femotomols/mg. Nevertheless, at our institution patients with ER-positive metastatic breast cancer have a higher response rate to chemotherapy and survive longer than their ER-negative counterparts.

Antineoplastic Agents↗