Effects of acid-base changes on human ureteric smooth muscle contractility.

Wide fluctuations of both urinary pH and the partial pressure of CO2 (PCO2) occur in normal physiological circumstances and in a variety of pathological conditions. However, the effect of extracellular pH on the contractility of human ureteric muscle has not been clearly defined. This study has established, using a microsuperfusion technique, that an increased superfusate PCO2 increases the magnitude of the phasic contraction to electrical field stimulation. A similar extracellular acidosis induced by alteration of the [HCO3-], at constant [Na+] and free [Ca2+], was without significant effect. Furthermore, when both superfusate PCO2 and [HCO3-] were simultaneously increased at constant pH the contractile response was similar to that when PCO2 alone was raised. These observations suggest that the changes of tension were mediated by intracellular pH changes, providing it is assumed that the ureteric smooth muscle cell membrane is permeable to CO2 but impermeable to H+ and HCO3-. The occurrence of an increase of force in the presence of an acidosis is a highly significant and unusual finding, since it has been assumed that the classical association between acidosis and negative inotropy, seen in cardiac muscle, was also applicable to smooth muscle.

Does extracorporeal shockwave lithotripsy cause hypertension?

Several series have suggested that the incidence of hypertension following extracorporeal shockwave lithotripsy (ESWL) may be as high as 8%. In this study, changes in blood pressure and the incidence of hypertension have been observed in 733 patients 12 to 44 months after renal ESWL on the Dornier HM3. The incidence of hypertension following ESWL was 8.1%. In patients with a pre-ESWL diastolic pressure less than 90 mmHg, the incidence of those with a diastolic greater than or equal to 100 mm Hg post-operatively was significantly greater than that predicted by historical data. There was no overall change in the mean blood pressure of the group. The hypertensive risk of ESWL remains unclear. However, blood pressure surveillance should be performed following ESWL and a prospective study is required.

Indomethacin as prophylaxis against ureteral colic following extracorporeal shock wave lithotripsy.

Ureteral colic occurs in 24 to 34 per cent of all patients following extracorporeal shock wave lithotripsy. Recent research has shown prostaglandin synthetase inhibitors to be effective in relieving the pain associated with ureteral colic. Our prospective, controlled, double-blind, randomized study was designed to test the efficacy of indomethacin in the prophylactic treatment of pain after extracorporeal shock wave lithotripsy. Patients undergoing extracorporeal shock wave lithotripsy were randomized into 2 groups. Group 1 received 100 mg. indomethacin suppositories twice daily and group 2 received placebo suppositories. After extracorporeal shock wave lithotripsy 2 analgesics were available to the patients: oral co-dydramol or intramuscular pethidine was offered in the normal manner by the nursing staff. The pre-extracorporeal shock wave lithotripsy x-ray was used to make a quantitative estimate of the total stone burden in each patient. The post-extracorporeal shock wave lithotripsy analgesic requirement was used to compare the 2 groups. Of 112 patients recruited to the study 55 received indomethacin and 57 received placebo. The request for analgesia in the 2 groups was not different (28 of 55 and 33 of 57, respectively). However, in the indomethacin group only 6 patients required pethidine (10 doses), compared to 18 (41 doses) in the placebo group. This difference is statistically significant (p less than 0.01). There was no difference between the 2 groups in the occurrence of ureteral steinstrasse. Indomethacin has been shown to be effective in the prophylactic treatment of ureteral colic after lithotripsy.

Is extracorporeal shockwave lithotripsy suitable treatment for lower ureteric stones?

Forty patients with lower ureteric calculi for which intervention was considered desirable have been treated by in situ extracorporeal shockwave lithotripsy (ESWL) on the Dornier HM3 Lithotripter using a modified technique. Stone localisation was satisfactory in all patients. Adequate disintegration was achieved in 90% of patients following one treatment; 34 patients have been followed up for at least 3 months and 27 of these are stone-free (79%). Treatment failed in 4 patients and 2 of these had dense lower ureteric stone streets as a result of previous ESWL. The retreatment rate, post-treatment auxiliary procedure rate and complication rate were minimal. It was concluded that in situ ESWL is an effective and safe method for treating certain selected lower ureteric stones and should be considered as a feasible alternative to the more conventional methods of treatment.

The action of the prostaglandins on isolated human ureteric smooth muscle.

A study has been carried out on the actions of the prostaglandins E2 and F2 alpha and their synthesis inhibitors, indomethacin and diclofenac sodium, upon isolated human ureteric smooth muscle, using the technique of microsuperfusion designed to ensure good tissue viability. Indomethacin and diclofenac sodium were shown to abolish almost completely the contractile response of ureteric muscle to electrical field stimulation. Contractile activity, in the presence of the inhibitors, could be restored by prostaglandin E2 or F2 alpha or by increasing the external potassium concentration, [K+]O, of the superfusate. Prostaglandin E2 or F2 alpha alone were shown to increase dramatically both the phasic and tonic component of the electrically stimulated contractions, on occasions inducing spontaneous activity. A possible mechanism of action was elucidated with an electrophysiological technique using intracellular microelectrodes. The mean membrane potential recorded was 54.7 mV (SD +/- 10 mV, n = 15). The depolarising action of raising [K+]O was demonstrated and prostaglandin F2 alpha (3 x 10(-6) M) was shown to produce a small depolarisation of the ureteric muscle cell membrane.

Effect of meteorological conditions on scintillation fading in the oxygen absorption region.

The effect of the absorption mechanism on the amplitude of the scintillations on a 4-km line of sight link at 54.5 GHz in different meteorological conditions is examined. When atmospheric temperature turbulence is dominant, the absorption mechanism causes the amplitude of the scintillations to be significantly increased for the large outer scale of turbulence sizes. When water vapor pressure fluctuations begin to dominate, the enhancement of the scintillations is suppressed, and the effect of the absorption mechanism on the amplitude scintillations is minimal.

Mercury poisoning after disc-battery ingestion.

A case is described of a 2-year-old girl who swallowed an alkaline disc battery containing mercuric oxide. Two days after ingestion it disintegrated in the stomach necessitating laparotomy to remove the battery casing and most of its contents. Postoperatively her blood mercury concentration rose to 340 micrograms/l and subsequently she developed small bowel obstruction due to adhesions. She was treated with dimercaprol but blood mercury concentrations did not fall until after a second laparotomy to relieve the obstruction and to remove residual mercury salts from the colon. The corrosive effects of swallowed disc batteries are well documented. The maximum blood concentration of mercury reported in this case is 17 times the 'acceptable level of mercury in the blood' and nearly double the highest level recorded previously after disc-battery ingestion. A policy for management of swallowed batteries is suggested.

Formaldehyde levels in homes insulated with urea-formaldehyde foam.

Twenty seven UFFI homes in Colorado and Wisconsin were sampled for formaldehyde levels. The formaldehyde concentrations found in these homes averaged 0.059 ppm. Two homes were monitored for an extended period to determine the impact of ambient climatic conditions.

Contamination of commercial blood products by di-2-ethylhexyl phthalate and mono-2-ethylhexyl phthalate.

Blood fractionation products obtained from three different manufacturers were analyzed to determine if either mono-2-ethylhexyl phthalate (MEHP) or di-2-ethylhexyl phthalate (DEHP) were contaminants of any of the fractionated proteins. The only protein fraction to contain DEHP was factor IX (23 micrograms/ml) from one company. However, MEHP was detected in low levels in several of the 5% normal serum albumin, 5% plasma protein fraction, factor VIII and factor IX samples. 25% normal serum albumin contained the highest level of MEHP with concentrations of up to 300 micrograms/ml (40% of the plasma level) depending on the sample. Attempts to remove MEHP using dialysis or ultrafiltration were unsuccessful and indicated a close association of the MEHP with albumin. There was a definite correlation between storage and transportation conditions and the level of MEHP in both plasma and 25% normal serum albumin. The highest levels of this phthalate acid ester were found in the products made from the plasma which had been shipped at ambient temperature. Contrary to published data, storage of plasma at -30 degrees C for up to 6 months prevented the accumulation of MEHP.

Cross-linking and relaxation of supercoiled DNA by psoralen and light.

Photoreaction of 4,5',8-trimethylpsoralen with superhelical ColE1 and ColE1amp DNA was studied. Changes in mobilities in agarose gels, formation of interstrand cross-links, and DNA strand breaks were determined. Psoralen and light treatment removed negative superhelical turns, and extensive treatments failed to produce positive superhelical turns in covalently closed plasmid DNA. The rate of relaxation of superhelical turns by psoralen Photobinding appeared to be directly proportional to the number of superhelical turns remaining. A unique reaction mechanism is presented to explain these results. By this interpretation the initial rate of psoralen photobinding to superhelical DNA was estimated to be 3 times that for linear DNA, and the ratio of cross-linking to monofuctional adducts appears to be dependent on the superhelical conformation of the DNA. The estimated ratio of psoralen molecules bound to DNA strand breaks was 1.7 . 10(4):1, and 70% of this breakage is caused by the light alone.

Repair of cross-linked DNA and survival of Escherichia coli treated with psoralen and light: effects of mutations influencing genetic recombination and DNA metabolism.

Repair of cross-linked DNA was studied in Escherichia coli strains carrying mutations affecting DNA metabolism. In wild-type cells, DNA strands cut during cross-link removal were rejoined during a subsequent incubation into high-molecular-weight molecules. This rejoining was dependent on gene products involved in genetic recombination. A close correlation was found relating recombination proficiency, the rate of strand rejoining, and formation of viable progeny after DNA cross-linking by treatment with psoralen and light. Wild-type cells and other mutants which were Rec+ (sbcB, recL, recL sbcB, recB recC sbcA, recB recC sbcB, xthA1, and xthA11) rejoined cut DNA strands at a rate of 0.8 +/- 0.1 min -1 at 37 degrees C and survived 53 to 71 cross-links per chromosome. recB, recC, recB recC, recF, or polA strains showed reduced rates of strand rejoining and survived 4 to 13 cross-links per chromosome. Recombination-deficient strains (recA, recB recC sbcB recF, recB recL) and lexA failed to rejoin DNA strands after crosslink removal and were unable to form colonies after treatments producing as few as one to two cross-links per chromosome. Strand rejoining occurred normally in cells with mutations affecting DNA replication (dnaA, danB, dnaG, and dnaE) under both permissive and nonpermissive conditions for chromosome replication. In a polA polB dnaE strain strand rejoining occurred at 32 degree C but not at 42 degree C, indicating that some DNA synthesis was required for formation of intact recombinant molecules.

Topography and kinetics of genetic recombination in Escherichia coli treated with psoralen and light.

Genetic exchanges appear to be involved in repair of cross-linked DNA. Kinetics for completion of repair and strand rejoining controlled by the recA(+) gene were examined in Escherichia coli treated with psoralen and light. The results suggest the following model for genetic recombination. After cross-linking treatment, cells in a population initiate repair in near synchrony. Removal of DNA cross-links, preparation of substrate for recombination, and initiation of the first recA-dependent event are completed in less than 1 min. Recombination events occur singly in each cell or chromosome, and require 2.3 +/- 0.4 min at 32 degrees for the recA(+)-dependent step. After completion of the first event, subsequent recombination events occur in a sequential or progressive fashion around the chromosome or in clusters which may consist of one or more domains of the folded chromosome. The time required to proceed to successive sites is either a constant, independent of the distance on the chromosome, or is quite small compared to 2.3 min. DNA substrate for recombination decays with approximate first-order kinetics and the rate is dependent on the number of unrepaired sites. Cell survival can be expressed as a competition between completion of all repair events and the simultaneous decay of chromosomes to forms not reparable by recombination.Equations relating kinetics for completion of repair, the size distribution of DNA molecules, and cell survival are derived for the above model, using as parameters only rate constants for recombination and decay of substrate, and number of events per chromosome. An excellent correlation is found between experimentally determined and theoretical values.

Role of ATP in removal of psoralen cross-links from DNA of Escherichia coli permeabilized by treatment with toluene.

Removal of interstrand cross-linked from DNA was examined in Escherichia coli permeabilized by treatment with toluene. Under these conditions, the reaction requires ATP and Mg2+, and the mechanism appears to be similar to that occurring in whole cells. Under optimum conditions, the rate constant was 0.06 min-1. Genetical, physical, and biochemical analysis of the repair process suggest the following mechanism. In an ATP-dependent reaction, the uvrA and uvrB gene products cleave a phosphodiester bond on the 5' side of one arm of the cross-link, producing a 3'-OH terminus. Subsequently, DNA polymerase I (5'-3' exonuclease activity) makes a second strand cut on the 3' side of the cross-link in the same DNA strand, completing removal of the covalent link between complementary strands. The second reaction did not occur in a uvrD- strain, which had normal levels of DNA polymerizing activity. The uvrD gene may regulate the specificity or activity of the 5'-3' exonuclease of DNA polymerase I in vivo.

Repair of cross-linked DNA in Escherichia coli.

The repair of DNA containing interstrand cross-links in Escherichia coli was studied by following the temporal sequence of DNA-related metabolic events in cells exposed to psoralen plus light. Mutations in some genes controlling replication, recombination, and repair strongly influence these specific events. Results reported here are consistent with a cross-link repair mechanism involving sequential excision and recombination.