Reduced effect of propofol at human {alpha}1{beta}2(N289M){gamma}2 and {alpha}2{beta}3(N290M){gamma}2 mutant GABA(A) receptors.

BACKGROUND: Propofol is an i.v. anaesthetic commonly used during general anaesthesia and intensive care. It is known that the second transmembrane segment of the beta subunit in the GABA(A) receptor is an important target for the effects of propofol; however, this has not been investigated in human receptors. The aim of this study was to investigate the effect of propofol on human beta2 and beta3 GABA(A) subunits with point mutations corresponding to the N265M mutation in the rat beta2 and beta3 subunits. METHODS: Asparagine-to-methionine replacement at amino acid position 289 and 290 (N289M and N290M) in the beta2 and beta3 GABA(A) receptor subunits, respectively, was accomplished by site-directed mutagenesis. Thereafter, subunits for three human wild-type (alpha1beta2gamma2, alpha2beta2gamma2, and alpha2beta3gamma2) and two mutant GABA(A) receptor channels [alpha1beta2(N289M)gamma2 and alpha2beta3(N290M)gamma2] were introduced into Xenopus oocytes and studied with two-electrode voltage clamp. RESULTS: The mutant receptors left-shifted the GABA concentration-response curve. In comparison with the wild-type receptors, both the positive modulatory and the agonistic effects of propofol were strongly reduced in potency and amplitude at both mutated GABA(A) channels. CONCLUSIONS: We demonstrate that N289M or N290M mutation in human GABA(A) beta2 and beta3 subunits increases sensitivity to GABA, which is in contrast to the corresponding rat N265M mutation. Furthermore, the N289M and N289M mutations reduce both the potentiation of GABA-induced currents and the direct effect of propofol on channels incorporating either of the mutated subunits, which confirms earlier findings concerning the corresponding mutation in rat receptors and knock-in mice.

Glutamate-induced currents reveal three functionally distinct NMDA receptor populations in rat dorsal horn - effects of peripheral nerve lesion and inflammation.

The importance of the N-methyl-D-aspartate (NMDA) receptor in various painful conditions is well established. The effects of peripheral nerve lesion or joint inflammation, as models of different pain states, on NMDA receptor-mediated currents and NMDA receptor subunit mRNA expression were therefore studied in acutely dissociated neurones from the rat spinal cord dorsal horn. In the neuronal population from control rats, all four NR2 subunits and both NR1 splice variants assayed were detected. A majority of neurones expressed mRNA for more than one NR2 subunit, and some neurones expressed all four NR2 subunits as well as both NR1 splice variants. The NR2B subunit was the most commonly expressed, while the NR2C was the rarest. Following nerve lesion, fewer neurones expressed NR2A compared to the control. The dose-response curve for glutamate-evoked NMDA receptor-mediated currents in the neurones was best described by a three-component fit, suggesting that three functionally distinct NMDA receptor populations are present in the dorsal horn. Minor changes in the dose-response curve after nerve lesion could not be ascribed with certainty to the lesion. Changes in other parameters of NMDA receptor-mediated currents were observed neither after nerve lesion nor after joint inflammation. In summary, the present work demonstrates that single dorsal horn neurones express mRNA for several NMDA receptor subunits. The glutamate dose-response curves indicate that there are three major types of NMDA receptors present in dorsal horn neurones. We also report a reduced expression of NR2A following peripheral nerve lesion.

Data warehousing as a basis for web-based documentation of data mining and analysis.

In this paper we present a case study for data warehousing intended to support data mining and analysis. We also describe a prototype for data retrieval. Further we discuss some technical issues related to a particular choice of a patient record environment.

Perforation of the bowel during SWL in prone position.

Perforation of the small bowel during SWL is reported for the first time. The patient was treated in the prone position for a ureteral stone with 4500 shockwaves. There were no underlying or predisposing factors for the damage to the gut with the exception of the large number of shockwaves at a high energy setting. It is concluded that SWL in the prone position with shockwaves traversing the peritoneal cavity carries a risk of damage to the bowel. A reduction of the number of shockwaves and the energy level should be considered in this setting.

The urological fate of young adults with myelomeningocele: a three decade follow-up study.

OBJECTIVE: Virtually all patients with myelomeningocele suffer from neurogenic disorder of the bladder. Problems with incontinence are common and there is also a risk of deterioration of renal function. The aim of the present study was to determine the long-term urological fate of this patient group. PATIENTS AND METHODS: Twelve young adults with myelomeningocele were interviewed and their records reviewed. RESULTS: The patients started clean intermittent catheterization (CIC) at the age of 10-21 years. Three patients underwent urological surgery prior to the start of CIC. This was also the case for 3 patients after having started CIC. Only 1 patient is completely continent. In the rest, the degree of incontinence varies. With few exceptions, the glomerular filtration rate was well preserved. Six of the incontinent patients had, on at least one occasion, denied incontinence to his doctor. CONCLUSION: It seems that the prognosis is good as far as renal function is concerned. However, continence is a prerequisite for good social adjustment. An obstacle for a rational treatment of incontinence, in the adolescent patient group, is the patient's strong tendency to underreport the actual incontinence situation. Thus, every effort must be made in order to obtain a correct history. In patients with validated incontinence, an aggressive treatment policy, including surgical intervention, is justified.

Evaluation of single sample clearance calculations in 902 patients. A comparison of multiple and single sample techniques.

PURPOSE: To derive new formulae for the calculation of single sample clearance of the contrast medium iohexol and to compare the formulae to a selection of existing single sample clearance formulae derived for the calculation of 51Cr-EDTA and 99mTc-DTPA clearance. MATERIAL AND METHODS: Glomerular filtration rate (GFR) was calculated from total plasma clearance of iohexol used for urography in 902 patients. Two plasma samples were drawn in each patient. Automated x-ray fluorescence analysis equipment was used for the plasma iodine analysis. Single and multiple sample iohexol clearance values were compared. In 77 patients the multiple sample clearance values were additionally compared to a 51Cr-EDTA clearance performed simultaneously or within 14 days. RESULTS: The precision of the results calculated by the existing single sample clearance formulae and the derived iohexol single sample clearance formulae were essentially the same. The most precise of the derived formulae was that based on the Bak Christensen & Groth formula. The correlation between multiple sample clearance of iohexol and 51Cr-EDTA was high (r = 0.918). CONCLUSION: Iohexol can substitute 51Cr-EDTA for GFR measurement. A valid GFR can be calculated from a single plasma sample determination of iohexol clearance using either the existing formulae or the new formulae derived from the present study.

Thermal injury during TUMT.

A 71-year-old man was treated with transurethral microwave thermotherapy because of symptoms of benign prostatic hyperplasia. The treatment session was performed without any abnormal complaints from the patient. Two hours post-treatment the patient felt pain in his penile shaft and noticed a wound. A thorough investigation revealed that the only possible explanation for the injury was a dislocation of the catheter.

Monitoring of renal pelvic pressure in patients with hydronephrosis.

A diagnostic method for the determination of obstructions in the pelvoureteral junction in patients with suspected idiopathic hydronephrosis is described and discussed. Two microtransducer catheters (MTCs) with infusion lumens are inserted under fluoroscopic control, one into the renal pelvis and the other in the perirenal space as a reference. The pressure values obtained are stored on a portable microcomputer system, carried by the ambulatory patients. Renal pelvic pressure, intra-abdominal pressure and differential pressure are calculated and displayed as time-pressure diagrams on a plotter. The pressures can be measured for long periods (3-24 h). Furthermore, steady state conditions can be evaluated during pelvic infusion of saline. The results from the pressure measurements are compared with clinical and radiological evaluations. Our results show that this method of long-term monitoring of intrapelvic pressure together with intra-abdominal pressure contributes to the evaluation of patients with suspected pelvoureteral obstructions and complements other methods in the preoperative investigation. However, this study reveals difficulties with measurements of intra-abdominal pressure. Carrying the equipment was not inconvenient for the patients.

Lymph leakage after staging pelvic lymphadenectomy for prostatic carcinoma with and without heparin prophylaxis.

The effect of heparin prophylaxis on lymph leakage and lymphocele formation was observed in a randomized, prospective, consecutive study of 48 patients undergoing lymph node dissection for staging carcinoma of the prostate. Subcutaneous low-dose heparin was given to 24 patients, and 24 without heparin prophylaxis constituted the control group. Lymph leakage per day was significantly greater and the leakage period longer in the heparin group than in the controls. The total of leaked lymph was notably greater and the incidence of lymphocele seven times higher in the heparin group than in the controls. All lymphoceles disappeared spontaneously in the first postoperative year. The results suggest high risk of prolonged lymph leakage and of lymphocele formation when low-dose heparin prophylaxis is given to patients undergoing a staging operation for prostatic carcinoma.

Carcinoma of the penis. Treatment by surgery or combined bleomycin and radiation therapy.

Forty-four patients with squamous cell carcinoma of the penis stage T1-T2, N0 were either treated surgically (n = 19) or with a combination of irradiation and bleomycin (n = 25). The overall actuarial survival rate was 80% at 3 years, 77% at 5 years and 60% at 10 years. The result of irradiation treatment combined with bleomycin was in stage N0 equivalent to that of surgical therapy. The non-surgical treatment had the advantage of preserved sexual ability.

Sexual function in men after radical cystectomy with or without urethrectomy.

Sexual function was evaluated in 21 patients with bladder carcinoma who had undergone radical cystectomy either with (n = 9) or without (n = 12) excision of the urethra. All patients received preoperative radiotherapy, and the cystectomy was done by a nerve-sparing surgical technique. At follow-up all patients reported normal sexual desire and tactile sexual activity. Eight of the 12 patients in whom the urethra was preserved could achieve penile erection and orgasm to tactile stimulation, and five of them had sufficient strength and duration of erection for sexual intercourse. Two of the nine patients in whom the urethra was removed-had weak erections insufficient for intercourse; three could experience orgasm. These results show that when cystectomy is done by a nerve-sparing technique and without urethrectomy there is more chance of preserving sexual function than when simultaneous urethrectomy is done.

Contrast media and pain in patients with acute ureteral stone obstruction. A comparative study with iohexol and metrizoate.

A randomized study was conducted in 43 patients who were in pain due to acute ureteral obstruction. Emergency urography was performed in all patients, using either a low osmolar non-ionic (iohexol) or a high osmolar ionic (metrizoate) contrast medium. Increase of pain following injection of contrast media was found in 56 percent of all patients. Increase of pain occurred with both contrast media without any difference between the degree of pain nor the number of patients who experienced an increase of pain. Delayed excretion was considered the only reliable indicator of the degree of obstruction in the present study. Nineteen (68%) of the 28 patients with a delayed excretion greater than 10 min experienced increased pain while the incidence of pain increase was significantly lower (33%) in patients without that sign of ureteral obstruction (p less than 0.05). The increase of pain was not associated with a simultaneous increase of the mean arterial blood pressure.

Renal cell carcinoma in a renal cyst: a case report and review of the literature.

We report a case of renal cell carcinoma within a simple renal cyst in the lower pole of the right kidney. Excretory urography showed a mass and ultrasonography revealed multiple renal cysts with a solid component arising from the wall in 1. This finding also was visualized by computerized tomography. Analysis of the cystic fluid showed a high cholesterol level but negative cytological results. At operation a 7 mm. tumor arose from the wall of the cyst. Histopathological examination showed grade 3 renal cell carcinoma with an aneuploid deoxyribonucleic acid content.

Central and renal haemodynamic effects of intravenous infusion of non-ionic and ionic contrast media. An experimental investigation in the pig.

The central and renal haemodynamic effects after intravenous infusion (1 ml/s) of a non-ionic (iohexol) and an ionic (metrizoate) contrast medium were investigated in 16 pigs. The injected contrast media induced marked haemodynamic changes compared with normal saline. However, there were no significant differences between the ionic and the non-ionic media. It was concluded that the effects were only partially caused by an increase in the blood volume due to the injected volume. In addition, the effects related to the viscosity, the osmolality and other not specified pharmacodynamic properties of the media are proposed to be of importance.

Antidiuretic hormone levels and the effect of indomethacin on ureteral colic.

We treated 25 patients with ureteral colic and urographically verified stones with 50 mg. indomethacin intravenously. Pain was relieved completely in 17 patients, while in 8 incomplete or no pain relief was achieved after the infusion of indomethacin. Patients completely relieved of pain had significantly higher levels of antidiuretic hormone in plasma before the infusion of indomethacin (18.2 plus or minus 3.4 pg./ml.) than patients with incomplete or no pain relief (7.2 plus or minus 1.3 pg./ml.) (p less than 0.01). These findings indicate that the volume status and/or the level of antidiuretic hormone may be of critical importance for pain relief after infusion of indomethacin in patients with ureteral colic.

Effects of indomethacin on central, renal and coronary hemodynamics. An experimental study in swine with unilateral ureteral obstruction.

The circulatory effects of intravenously administered indomethacin, a potent prostaglandin synthesis inhibitor (0.8 mg/kg bw) were investigated in pigs with unilateral ureteral obstruction. The drug induced a marked but transient increase in systemic arterial pressure (+53%, p less than 0.02) and pulmonary arterial (+81%, p less than 0.02) pressure without any changes in left or right sided filling pressures, cardiac output or heart rate. Coronary blood flow remained unchanged and renal venous blood flow decreased (-26%, p less than 0.02). Renal pelvic pressure decreased (-20%, p less than 0.02). Thus systemic (SVR), pulmonary (PVR) and coronary vascular resistance (CVR) and renal vascular resistance (RVR) on the obstructed side increased (SVR + 73%, p less than 0.02; PVR + 140%, p less than 0.02; CVR + 53%, p less than 0.02 and RVR + 107%, p less than 0.02 respectively). Even if one takes into consideration other factors than ureteral obstruction contributing to these reactions, e.g. low volume load, anaesthesia, surgical trauma and species differences, care is advised in treating patients with coronary artery disease or obstructive lung disease with indomethacin.

Effects of saline load, Roentgen contrast medium and indomethacin on diuresis and pelvic pressure in the acute obstructed kidney. An experimental study.

In anaesthetised pigs indomethacin (2.5 mg/kg body weight) immediately reduced pelvic pressure above unilaterally and bilaterally totally occluded ureters. Repeated administration of the same dose caused a cumulative reduction of pelvic pressure. In animals with a kidney working against a partial obstruction of the ureter, indomethacin reduced urine production by more than 50% within 15 to 30 min. It was also shown that the effect of indomethacin on the pelvic pressure was dependent on the fluid load of the animals. Rapid infusion of saline or X-ray contrast medium counteracted the pressure fall induced by indomethacin.