Growth failure in gastrointestinal diseases.
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Cystic Fibrosis↗
Biomedical subjects
E Mayer
Publications and source records attributed to E Mayer.
Striatal graft-associated recovery of a lesion-induced performance deficit in the rat requires learning to use the transplant.
Peformance in a prelearned choice reaction time task was studied 6 months after surgery in rats with ibotenate-induced lesions of the striatum either with or without striatal grafts, and in sham-operated controls. The long postoperative interval allowed full transplant maturation and the establishment of appropriate connections by the transplants. The animals were trained prior to surgery on a visual choice reaction time task which requires that a movement is made away from stimuli signalling reward. The use of multiple measures allowed a thorough analysis of several aspects of the animals' performance. Whilst sham-operated control animals recovered normal (preoperative) performance rapidly, the lesioned animals had a severe performance deficit. Although the transplanted animals were initially at least as deficient in performance as the lesioned group, repeated testing led to an amelioration of the lesion-induced deficit according to two distinct measures of spatial bias and reaction time. On a third measure, latency to complete the lateralized movement, the grafted group were initially worse than the lesioned group but repeated testing resulted in significant recovery. These results suggest that postoperative training may help to optimize the efficacy of graft-induced recovery, and that animals may need to learn to use a transplant in order for it to confer functional benefit in complex prelearned tasks.
Journal Article↗
Characterization of large-conductance chloride channels in rabbit colonic smooth muscle.
1. A large-conductance Cl- channel was characterized in cell-free membrane patches from the rabbit longitudinal colonic smooth muscle using the patch clamp technique. In addition, the regulation of these channels by neurokinin-1 (NK-1) receptor agonists and G proteins was studied. 2. No spontaneous channel activity was observed in cell-attached patches at the cell resting potential, or in excised patches at pipette potentials (Vp) between -20 and 20 mV. In excised patches, channel activity could be induced in thirty-six out of ninety-six patches by holding the patch at Vp values more negative than -60 mV or more positive than 60 mV. Once induced, the channel showed a bell-shaped voltage activation curve in high symmetric [Cl-], with maximal open probability between 20 and -5 mV. Varying cytosolic calcium concentration ([Ca2+]) between 5 x 10(-8) M and 1.0 mM had no effect on the voltage activation of the channel. 3. In inside-out and outside-out patches, when pipette and bath solutions contained equal [Cl-] (130 mM), the anion channel showed a linear current-voltage (I-V) relationship between -60 and 60 mV with a slope conductance of 309 +/- 20 pS (n = 13). Reversal potential measurements indicated that the channel was selective for Cl- over Na+ and K+ (PCl/PNa = 6:1). 4. Channel openings from the closed state to the full open state as well as transitions through smaller conductance states were observed. The smallest detectable substate had a conductance of 15.6 pS. Based on the similarities in selectivity and linearity of the I-V curve of the smaller conductances with the full open state, and kinetic analysis of channel activity, it is concluded that the large conductance channel is composed of multiple substates which can either open and close independently, or simultaneously via a main gate. 5. The stilbene derivative diiso-thiocyanato-stilbene-disulphonic acid (DIDS) and the diphenylamine-2-carboxylate analogue 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) caused a dose-dependent, reversible flicker block of the small conductance and significantly reduced the macroscopic current flow through the channel. 6. In quiescent outside-out patches, when the pipette contained a 140 mM-CsCl solution with 10(-6) M-CaCl2, 1.2 mM-MgCl2 and 1 mM-GTP, and the bath contained Ringer solution, addition of the NK-1 receptor antagonists substance P methylester resulted in activation of the full conductance state and of smaller substates.(ABSTRACT TRUNCATED AT 400 WORDS)
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
Surgical treatment of myocardial bridging causing coronary artery obstruction.
Nine patients with obstruction of coronary artery blood flow caused by myocardial bridging underwent surgery after failure of medical treatment. The diagnoses were made angiographically at rest or during beta-stimulation. Impaired blood flow was found only in the left anterior descending artery in seven patients and additionally in the diagonal branch in two. The operations, performed with cardiopulmonary bypass consisted of complete dissection of the overlying myocardium. All patients survived the operation. Major intraoperative complications were accidental opening of the right ventricle in two patients. Postoperative scintigraphic and angiographic studies demonstrated restoration of coronary flow and myocardial perfusion without residual myocardial bridges under beta-stimulation. Surgical relief of myocardial ischemia due to systolic compression of intramyocardial coronary arteries can be accomplished with low operative risk and with excellent functional results.
Adult↗
Efficacy of phosphodiesterase inhibitor enoximone in management of postcardiotomy cardiogenic shock.
The efficacy of the phosphodiesterase inhibitor enoximone for reversal of severe postcardiotomy low cardiac output syndrome was investigated in 13 cases of cardiogenic shock refractory to conventional treatment consisting of beta-adrenergic agonists (n = 13) combined with vasodilators (n = 7), and intra-aortic balloon counterpulsation (n = 5). Following a bolus of 1 mg/kg enoximone, cardiac and stroke volume indices increased from 1.56 +/- 0.27 l/min/m2 and 16.3 +/- 3.3 ml/m2, respectively, to 2.72 +/- 0.67 and 27.8 +/- 7.1 (both p < 0.001). Mean arterial pressure fell, from 77 +/- 11 to 68 +/- 9 mmHg (p < 0.05), as did atrial filling pressures (LAP and RAP), LAP from 21.3 +/- 5.5 to 15.9 +/- 2.9 and RAP from 16.6 +/- 2.3 to 13.7 +/- 2.1 mmHg (both p < 0.01). The heart rate rose by only 5%. Enoximone therapy was maintained by a continuous infusion (5-7.5 micrograms/kg/min) for 40.6 +/- 8.6 hours (range 14-92). All hemodynamic parameters remained stable throughout treatment. Six patients died of sepsis and/or multiorgan failure but seven were discharged from hospital. Enoximone thus improved hemodynamic performance significantly in cardiogenic shock after open-heart surgery. It also has proved valuable in cardiac failure when conventional therapy was unsuccessful.
Aged↗
The effect of basic fibroblast growth factor and omentopexy on revascularization and epithelial regeneration of heterotopic rat tracheal isografts.
Donor airway ischemia is a significant problem after clinical lung transplantation despite the use of omentopexy for accelerated local bronchial revascularization. Several growth factors have been shown to induce angiogenesis in vitro and in vivo. In the present study the quantitative effects on tracheal revascularization and epithelial regeneration of omentopexy and continuous local administration of basic fibroblast growth factor were investigated in a heterotopic rat tracheal isograft model. Tracheas were harvested from donor rats and heterotopically implanted into the omentum of syngeneic recipient rats. Animals were randomly assigned to study groups differing only in treatment of the tracheal segments: omental wrap for 2, 7, or 14 days; omental wrap plus continuous local administration of basic fibroblast growth factor for 7 or 14 days; or omental wrap plus local application of saline for 7 or 14 days. Two, 7, or 14 days after the animals were put to death, the vascularity of the tracheal segments and attached omentum and the tracheal epithelial morphology were assessed in a blinded fashion with use of light microscopy and morphometric image analysis. Vascularity in tracheal segments treated with basic fibroblast growth factor was significantly (p less than 0.05) greater than in control tracheas after 7 and 14 days. Epithelial regeneration was also improved in the basic fibroblast growth factor-treated groups at days 7 and 14 (p less than 0.05). We conclude that continuous local administration of basic fibroblast growth factor enhances early revascularization of tracheal segments induced by omentopexy and accelerates epithelial regeneration in a heterotopic rat tracheal isograft model.
Animals↗
Equivalent eighteen-hour lung preservation with low-potassium dextran or Euro-Collins solution after prostaglandin E1 infusion.
Improved techniques of pulmonary preservation would help alleviate the critical shortage of donor organs in lung transplantation and would improve early graft function. A previous study demonstrated that cold pulmonary artery flush with low-potassium dextran solution was superior to Euro-Collins solution in preservation of canine lung allografts stored for 12 hours when no pulmonary vasodilator was used before donor lung flush. The present study was designed to determine whether donor pretreatment with prostaglandin E1 would affect the superiority of low-potassium dextran as a preservation solution. Prostaglandin E1 was infused (50 micrograms/min) in 12 donor dogs until potent vasodilation was demonstrated. Low-pressure pulmonary artery flush (50 ml/kg) with either Euro-Collins or low-potassium dextran solution (n = 6 for each group) was performed at 4 degrees C in a randomized, blinded fashion. Heart-lung blocks were extracted and stored at 4 degrees C for 18 hours before left lung allografting. Inflatable cuffs were placed around each pulmonary artery, allowing independent study of the native and transplanted lungs. All 12 recipient dogs survived the 3-day assessment period. Lungs flushed and stored in Euro-Collins or low-potassium dextran solution provided equivalent gas exchange function on day 0 (arterial oxygen tension: Euro-Collins 289 +/- 105 mm Hg versus low-potassium dextran 265 +/- 111 mm Hg; mean +/- standard error of the mean) and on day 3 (Euro-Collins 516 +/- 45 mm Hg versus low-potassium dextran 354 +/- 77 mm Hg; p = 0.10). Mean pulmonary artery pressures in the transplanted lung were not significantly different in the Euro-Collins and low-potassium dextran groups on day 0 (21.4 +/- 2 mm Hg versus 33.7 +/- 5 mm Hg, respectively; p = 0.09) or on day 3 (20.2 +/- 2.7 mm Hg versus 24.2 +/- 5.1 mm Hg, respectively; p = 0.50). We conclude that there was no advantage of low-potassium dextran over Euro-Collins as a flush solution in this 18-hour canine single lung allograft model in which prostaglandin E1 was administered before pulmonary artery flush.
Alprostadil↗
Reliable thirty-hour lung preservation by donor lung hyperinflation.
We examined the hypothesis that the degree of inflation of the lungs at the time of harvest may have an important role in postpreservation function. Lungs of donor dogs randomly assigned to groups 1 (n = 5) and 2 (n = 5) were ventilated with large tidal volumes (tidal volume, 25 ml/kg; positive end-expiratory pressure, 5 cm H2O; respiratory rate, 12 breaths/min, inspired oxygen fraction 1.0) and were inflated to 30 cm H2O for 15 seconds before pulmonary artery flush and again immediately before tracheal crossclamping. In group 3 (n = 5) donor lungs were normally ventilated (tidal volume, 12.5 ml/kg, positive end-expiratory pressure 0 cm H2O; respiratory rate 12 breaths/min, inspired oxygen fraction, 1.0) and were not hyperinflated before pulmonary artery flushing; the trachea was crossclamped at end-inspiration. In groups 1 and 3 a large bolus (25 micrograms/kg) of prostaglandin E1 was injected into the pulmonary artery before flushing and was also added to the pulmonary artery flush solution (500 micrograms/L). A rapid (approximately 50 seconds), high-volume mm Hg), hypothermic (4 degrees C) pulmonary artery flush was performed in all hypothermic (4 degrees C) pulmonary artery flush was performed in all groups with modified Euro-Collins solution. Heart-lung blocks were stored at 4 degrees C for approximately 29 hours before left single lung allografting. An inflatable cuff was placed around the recipient right pulmonary artery, allowing independent study of the transplanted lung. Hyperinflated lungs harvested with or without prostaglandin E1 provided equivalently excellent early posttransplant function (arterial oxygen tension [mean +/- standard deviation]: group 1; 503 +/- 45, vs group 2; 529 +/- 150 mm Hg; inspired oxygen fraction 1.0). Mean arterial oxygen tension was significantly lower in group 3 (116 +/- 78 mm Hg) than in either groups 1 or 2 (p < 0.0002 for either comparison). Copious reperfusion pulmonary edema was a constant feature in group 3 but was not seen in groups 1 and 2. All 10 recipients in groups 1 and 2 survived the 3-day assessment period without difficulty; two of the five recipients in group 3 died during initial unilateral perfusion of the transplanted lung. Donor hyperventilation and inflation to 30 cm H2O before hypothermic storage can help provide excellent posttransplantation lung function after 30-hour preservation, with or without prostaglandin E1 pretreatment. We speculate that this improvement may be due to effects of increased lung volume on pulmonary vascular tone and/or surfactant metabolism.
Alprostadil↗
[Isolated lung transplantation. I. Indications and criteria for patient selection].
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Adult↗
[Isolated lung transplantation. II. Surgical procedure, complications and results].
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Cause of Death↗
Reliable eighteen-hour lung preservation at 4 degrees and 10 degrees C by pulmonary artery flush after high-dose prostaglandin E1 administration.
Pulmonary preservation is improved by hypothermia, but the optimal preservation temperature is not known. The effects of two different preservation temperatures, 4 degrees and 10 degrees C, on lung function were studied in a canine left lung allograft survival model allowing selective perfusion of either lung. After donor treatment with high-dose prostaglandin E1, (25 micrograms/kg), lungs were flushed with modified Euro-Collins solution (50 ml/kg) and stored in Euro-Collins solution for 18 hours at 4 degrees C in group I (n = 8) and 10 degrees C in group II (n = 6). Pulmonary gas exchange and hemodynamics were compared on the day of transplantation (day 0) and 3 days later (day 3). Rapid, high-flow, low-pressure flush was achieved uniformly in both groups (flush time: group I, 35.1 +/- 2.4 second; group II, 35.3 +/- 3.0 seconds; p = 0.96; flush pressure: group I, 9.8 +/- 0.7 mm Hg; group II, 10.1 +/- 1.1 mm Hg; p = 0.8). Transplanted lungs provided similar excellent oxygenation in both groups on day 0 (arterial oxygen tension, group I, 451 +/- 82 mm Hg; group II, 497 +/- 37 mm Hg; p = 0.61; inspired oxygen fraction = 1.0) and day 3 (arterial oxygen tension, group I, 551 +/- 57 mm Hg; group II, 587 +/- 19 mm Hg; p = 0.55), with a statistically significant improvement from day 0 to day 3 in both groups (group I, p = 0.034; group II, p = 0.038). There was no difference in arterial carbon dioxide tension, base excess, cardiac output, blood pressure or pulmonary artery pressure between the two groups. We conclude that a large bolus of prostaglandin E1 into the pulmonary artery produces a high-flow, low-pressure flush with modified Euro-Collins solution; with this technique, equivalent, reliable 18-hour lung preservation can be achieved at 4 degrees and 10 degrees C flush and storage temperatures.
Alprostadil↗
[Revascularization of heterotopic isotransplants of the rat trachea using an omentum flap].
Donor airway ischemia remains a significant problem following lung transplantation. An acceleration of local bronchial revascularization would be advantageous for bronchial healing. In the present study, the quantitative effects of omentopexy on tracheal revascularization and epithelial regeneration were investigated in a heterotopic rat tracheal isograft model. Tracheal segments were harvested from donor rats and heterotopically implanted into the omentum of syngeneic recipient rats. Tracheal segments were wrapped for 2 days (group 2), 7 days (group 3) or 14 days (group 4). Tracheal segments in group 1 were harvested and not re-implanted. Following sacrifice of the animals after 2, 7 or 14 days, the vascularity of the tracheas and the tracheal epithelial morphology were assessed histologically using morphometric image analysis. The vascularity of tracheal segments was significantly higher in group 1 (native tracheas) compared to all other groups. Vascularity in group 4 segments (omental wrap for 14 days) was significantly greater than in group 3 segments (omental wrap for 7 days). Tracheal epithelial morphology was characterized by non-confluent single epithelial cells at day 2, a confluent multilayered nonciliated epithelium after 7 days of omental wrap and a morphologically normal epithelium after 14 days of omental wrap. Our new heterotopic rat tracheal isograft model allows histologic assessment and quantification of local revascularization and epithelial regeneration of tracheal segments by omentopexy.
Anastomosis, Surgical↗
Alkali cation effect on carbonyl-hemoglobin's and -myoglobin's conformer populations when exposed to freeze-concentration of their phosphate-buffered aqueous solutions.
Freeze-concentrated aqueous phosphate-buffered (pH 6.8) solutions of carbonyl-hemoglobin (HbCO) and -myoglobin (MbCO) were investigated by Fourier-transform infrared spectroscopy for the effect of alkali cation on the population of conformers. When using sodium phosphates as buffer components, HbCO was transformed from conformer III (at approximately 1951 cm-1) which is the dominant form at ambient temperatures, into conformer IV (at buffer concentration at a given temperature. The conformational changes started slightly below the temperature where ice began to crystallize and the remaining solution became freeze-concentrated, and they were reversible for HbCO. For MbCO in 0.5 M sodium phosphate buffer solution, however, they were irreversible and MbCO denatured completely. When potassium phosphate salts were used for preparing the buffer at the same pH of 6.8, little or no transformation of conformer III into conformer IV was observed. The conformational changes induced by sodium salts are attributed to a decrease in pH and it is shown by infrared spectroscopy that during freeze concentration drastic changes in composition of the two buffer components H2PO4-/HPO(2)4- occur, the acid component increasing strongly relative to the base component. Supersaturation is also important because change from conformer III to IV requires a minimum concentration of sodium salts: whereas 0.1 M sodium phosphate buffer concentration shows a strong effect, 0.03 M concentration does not and therefore behaves like a potassium phosphate buffer.
Animals↗
Role of angiotensin and sodium intake in cardiac noradrenaline release.
The effects of exogenous and of endogenous angiotensin on noradrenaline overflow were investigated in saline perfused rat hearts with intact sympathetic nerves. The overflow of endogenous noradrenaline induced by electrical stimulation of the left stellate ganglion was determined in the coronary venous effluent by HPLC. The activity of the renin-angiotensin system was modulated by varying of the nutritional sodium load prior to the experiments. Endogenous angiotensin formation was blocked by angiotensin-converting enzyme inhibitors. Following high sodium intake, both angiotensin II (100 nmol/l) and angiotensin I (1 mumol/l) caused a marked increase of the electrically evoked noradrenaline overflow. After inhibition of the angiotensin-converting enzyme using captopril (350 nmol/l) or ramiprilat (50 nmol/l), angiotensin I (1 mumol/l) did not enhance noradrenaline overflow. This indicates an active cardiac angiotensin conversion, since the sole administration of captopril and ramiprilat did not affect noradrenaline overflow in rats with high sodium intake. Following low sodium intake, neither angiotensin II (100 nmol/l) nor angiotensin I (1 mumol/l) significantly affected noradrenaline overflow. Both captopril and ramiprilat, however, significantly reduced noradrenaline overflow induced by electrical stimulation, suggesting a facilitory action of endogenous angiotensin under these conditions. This concept was substantiated when evaluating the noradrenaline overflow during control stimulations. Following low sodium intake, stimulation evoked noradrenaline overflow was higher as compared to that after nutritional sodium load. The results are in keeping with a sodium-dependent intracardiac formation of angiotensin II which facilitates noradrenaline release from sympathetic nerve terminals. Following low sodium intake, cardiac angiotensin II formation is active, as indicated by the suppression of noradrenaline release by angiotensin-converting enzyme inhibitors and the ineffectiveness of exogenous application of angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin I↗
Simultaneous presentation of adenocarcinoma of prostate and transitional cell carcinoma of bladder.
Simultaneous presentation of transitional cell carcinoma of the bladder and adenocarcinoma of the prostate is not uncommon. Twenty-two patients were diagnosed as having simultaneous or concurrent presentation of prostate and bladder carcinomas between January 1970 and July 1986. The overall five-year survival was 40 percent, with patients presenting with prostate cancer doing better (50%) than those with bladder cancer (32%). Retrospective review of these cases suggests that primary therapy should be directed to the most advanced cancer. Incidental prostate cancer may be "cured" with a cystoprostatectomy and, when indicated, radiation therapy added postoperatively for the bladder cancer. Eleven patients presented with Stage A prostate cancer: 10 of the 11 were treated for their bladder cancer. Treatment was usually radical cystoprostatectomy with or without postoperative radiation. None died of prostate cancer. Patients presenting with advanced stage prostate cancer have had recurrence or have died of the cancer.
Adenocarcinoma↗
Genetic analysis of reproductive disorders in Israeli Holstein dairy cows.
The heritability of common reproductive disorders was asessed in Israeli Holstein cows. Data were collected from 76,000 calvings on 102 collective farms (kibbuts) over a 36-mo period. The disorders considered were those of retained placenta, abnormal lochia, endometritis, anestrus, ovarian cysts with anestrus and ovarian cysts with nymphomania. The statistical model included fixed effects of herd-year, month of calving, duration of previous pregnancy, interaction between calving difficulty and sex of offspring, and the random effect of the sire. Herd-year effects consituted 0.68 of the explained variance of the incidence of retained placenta and approximately 0.89 of all the other disorders. Sire and calving-month effects were significant (P<0.05) for all the disorders. Heritability estimates of the disorders were 0.01 for retained placenta, abnormal lochia, and endometritis; 0.02 for anestrus; and 0.03 for all disorders. Correlations between any two disorders did not exceed 0.20. High genetic correlations were found between retained placenta and either abnormal lochia (0.90) or endometritis (0.70), while moderate genetic correlations were found among each of these and anestrus (0.30). Reproductive disorders occur as part of a complex which may be efficiently controlled by management measures. Nevertheless, breeding for resistance to reproductive disorders may also be feasible by using appropriate sires evaluated on a large number of daughters.
Journal Article↗
A novel indicator system allows detection of point mutations conferring a Ner- phenotype of phage Mu.
A plasmid-based indicator system was constructed which allows the easy detection of point mutations within the ner gene of bacteriophage Mu and its regulatory region. Five mutants have been sequenced exhibiting point mutations within the ner gene itself or its upstream region. These data are discussed with respect to the activity of the Ner protein.
Amino Acid Sequence↗
The expression of the c-src+ proto-oncogene mRNA in foetal striatal tissue grafts.
We have studied by in situ hybridization the mRNA expression of the pp60c-src proto-oncogene in grafts of foetal striatal neurons implanted into the ibotenic acid lesioned adult rat neostriatum. Animals were studied at 5, 10, 15, 30 days and 4 months after transplantation. Using 35S-labelled specific oligonucleotide probes, high levels of mRNA for pp60c-src+ but not pp60c-src- were found in the normal embryonic striatum and in striatal grafts up to 1 month after implantation; no hybridization signal was obtained in the normal adult striatum or in 4-month old grafts. The data suggest that pp60c-src+ is highly expressed in developing, but not mature, neurons and may play a fundamental role in the maturation and differentiation of grafted embryonic striatal neurons.
Animals↗