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Biomedical subjects

G Lundgren

Publications and source records attributed to G Lundgren.

At least 73 records · Page 4Linked to original sources
PubMed1985

Distribution and elimination of the stereoisomers of soman and their effect on brain acetylcholine.

The four stereoisomers of soman (O-(1,2,2-trimethylpropyl)-methyl-fluorophosphonate) have been analyzed in vivo in mouse blood and tissues after administration of doses corresponding to 0.75 X LD50 of the two diastereoisomeric pairs of soman (Sc- and Rc-soman). The disappearance of the four isomers has been studied in vitro in the presence of enzymes involved in the toxicity and detoxification of soman, e.g., acetyl- and pseudocholinesterase, aliesterase, and phosphorylphosphatase. The effect of Sc- and Rc-soman on brain acetylcholine was studied in the mouse. The analytical methods used are based on gas chromatography-mass spectrometry with deuterated internal standards. Rc-Rp- and ScRp-soman, the two isomers that preferentially react with acetylcholinesterase, were found in blood and liver. In liver the concentration of ScRp was higher than that of RcRp and could be followed for 18 hr. In blood only ScRp could be found. Its presence there could be followed during 18 hr. The levels were, however, lower than in liver. The results indicate that the liver might be a depot for soman and that ScRp might be responsible for the delayed intoxication noted after treatment with antidotes. Rc-soman was found to have a more pronounced effect on the acetylcholine synthesizing system than has Sc-soman, which might explain its higher in vivo toxicity.

Acetylcholine↗
PubMed1985

Pancreatic transplantation in diabetes mellitus: present status.

Between December 1966 and June 1982, 269 transplantations of vascularized pancreas (whole or segmental) were undertaken in 254 diabetic patients throughout the world. Most of the transplantations were performed in patients with end-stage renal disease who also received kidney grafts; a few patients received pancreatic grafts only. About 25% of the pancreatic grafts are still functioning after periods of various lengths, the longest being five years. To the problem of how to handle the exocrine secretion there are two main approaches: 1) occlusion of the duct with a synthetic polymer and 2) pancreatico-enterostomy. A disadvantage of the former procedure is late fibrosis and atrophy of the endocrine tissue. With the latter method duct leakage and fistula development cannot be completely prevented. In either case, vascular complications cause graft failure in about 20% of the operations. The risk of rejection of the graft seems not to differ significantly from that concerning other allogeneic organs, including the kidney and heart. Most of the patients with a functioning pancreatic graft are normoglycemic: they have a normal or near-normal oral or intravenous glucose tolerance and an early insulin response to intravenous glucose tolerance and an early insulin response to intravenous glucose challenge. Whether the improvement of the motor and sensory nerve conduction velocities observed in some patients whose graft has functioned for a long time is due to the reversal of renal insufficiency or to insulin deficiency cannot yet be determined. At present, pancreas transplantation at Huddinge Hospital is performed only in conjunction with renal transplantation in patients with end-stage diabetic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Prevention of kidney graft diabetic nephropathy by pancreas transplantation in man.

Kidney graft biopsies were performed 2-3 yr after transplantation in eight type I (insulin-dependent) diabetic patients who had previously been subjected to kidney transplantation (six patients) or combined kidney and segmental pancreas transplantation (two patients). In five of the six patients that had undergone only kidney transplantation, light microscopic examination of the graft biopsy revealed changes compatible with diabetic nephropathy, and electron microscopic morphometry showed a thickening of the glomerular basement membrane (GBM). In the two patients who had been subjected to combined pancreas and kidney transplantation, the kidney graft biopsy showed no light microscopic changes suggestive of diabetic nephropathy, and electron microscopy showed no thickening of the GBM. Thus, it appears to be possible to prevent the recurrence of diabetic nephropathy in human kidney allografts by simultaneous pancreas transplantation.

Adolescent↗
PubMed1985

Intravenous foscarnet for the treatment of severe cytomegalovirus infection in allograft recipients.

Foscarnet, trisodium phosphonoformate, was administered intravenously to 6 immunosuppressed patients with life-threatening cytomegalovirus infection. Three of the patients were recipients of a kidney and 3 of a bone-marrow transplant. Favourable clinical responses were seen in 5 of the patients, 2 of whom were still in good health 5 and 8 months after the infection had cleared up. No toxic effect of the drug was detected. The results seem to justify further trials, in which foscarnet should be introduced at an earlier stage of the disease.

Adult↗
PubMed1985

Acyclovir prophylaxis in bone marrow transplant recipients.

Forty-two patients undergoing bone marrow transplantation were included in a randomised, double-blind and placebo controlled trial of prolonged acyclovir prophylaxis against infections with viruses of the herpes group. Twenty patients were allocated to receive acyclovir and 22 to receive placebo. Acyclovir or placebo was administered i.v. at a dose of 250 mg/m2 twice daily, starting 5 days before transplantation. At 5 weeks after transplantation, administration was changed to tablets, 400 mg three times daily (children less than 6 years, 200 mg three times daily) and continued until 6 months after transplantation. In the placebo group, 10 acute herpes simplex virus (HSV) infections occurred in 7 patients (5 HSV-1 and 2 HSV-2), and another patient repeatedly shed HSV in throat washings. Five patients developed herpes zoster. Among patients receiving acyclovir only one episode of HSV infection occurred and no herpes zoster. The difference in the number of infection episodes and the number of infected patients was strongly significant (p = 0.0002 and 0.0017, respectively). The only acyclovir patient who reactivated HSV was terminally ill, and it is highly likely that she did not absorb a sufficient amount of the orally administered drug to control infection. All HSV and varicella zoster virus (VZV) infections were reactivations, and 9 of 10 patients who developed HSV infections or shed virus had a pre-transplantation HSV IgG titer of greater than 10 000 (ELISA). Acyclovir had no effect on cytomegalovirus (CMV), time of engraftment, or graft versus host disease (GVHD). Apart from a possible allergic reaction (skin rash) to acyclovir tablets, no adverse reactions were seen during this long prophylaxis with acyclovir.

Acyclovir↗
PubMed1984

Stereoselectivity of enzymes involved in toxicity and detoxification of soman.

The fate of the four stereoisomers of soman [0-(1,2,2- trimethylpropyl )-methyl-fluoro phosphonate] has been studied a) in vivo in mouse blood and liver after IP injection of 0.75 X LD50 RC- and SC-soman respectively, and b) in vitro upon incubation with acetyl- und pseudocholinesterase, aliesterase and phosphorylphosphatase . The analytical method used is based on gas chromatography-mass spectrometry with deuterated internal standard. Most soman disappeared very rapidly from blood and liver. In liver, SCRP and RCRP , the two isomers that preferentially react with cholinesterase, could be detected. The level of SCRP , which was higher than that of RCRP , could be followed for 17-18 h. In blood only SCRP could be detected. The amounts found were fairly constant during the time period 2 min to 4h, and it could even be detected 17-18 h after soman administration.

Acetylcholinesterase↗
PubMed1984

Cytomegalovirus infection associated with and preceding chronic graft-versus-host disease.

Of 68 consecutive allogeneic bone marrow transplant patients, 53 survived more than three months after transplantation. Twenty-two (42%) developed chronic graft-versus-host disease (GVHD). Chronic GVHD was more common among patients who had previously experienced cytomegalovirus (CMV) infection (20/36, 56%) than among those without signs of active CMV infection (2/17, 12%) (P less than 0.01). The CMV infections preceded the development of chronic GVHD by a median of 128 days (range 23-322 days). Children below 14 years of age who had had CMV infection developed chronic GVHD as often as older patients (8/14 vs. 12/22). CMV infection may pave the way for chronic GVHD.

Adolescent↗
PubMed1984

Metallothionein in rabbit kidneys preserved for transplantation.

Thirteen rabbits were given repeated cadmium injections to achieve cadmium concentrations in kidney cortex ranging from 0.05 to 1 mmole Cd/kg wet weight. Another four animals served as controls. One kidney from each animal was frozen directly to -70 degrees C whereas the other kidney was kept for 24 hr at +4 degrees C in a preservative (Sachs' solution) to simulate conditions for preservation of human donor kidneys before transplantation. Protein binding of cadmium, zinc and copper in kidney homogenates and the concentration of metallothionein (MT) were measured in the kidney that was frozen directly and in the kidney that had been preserved. No gross differences in either the protein binding of cadmium, zinc and copper or in the MT content were seen between the directly frozen and preserved kidneys from the same animal. This indicates that MT is not rapidly broken down in rabbit kidneys which have been preserved similarly to human donor kidneys for 24 hr in a standard preservative solution prior to a transplantation.

Animals↗
PubMed1984

Selective decontamination of alimentary tract microbial flora in patients treated with bone marrow transplantation. A microbiological study.

14 patients undergoing bone marrow transplantation were studied regarding the oral and faecal microflora. Seven patients were given a multidrug regimen, directed against aerobic gram-negative rods and fungi, for local decontamination of the oral cavity and gastrointestinal tract. Seven other patients served as controls. The decontamination regimen was found to decrease the numbers of fungi in the oral cavity and to protect from new colonization. In the gastrointestinal tract aerobic gram-negative rods were eliminated in all patients and new colonization with acquired microorganisms was not observed even when the indigenous anaerobic flora had been disturbed by parenteral antibiotics. In the control group aerobic gram-negative rods and fungi were isolated from all patients during the observation period.

Adolescent↗
PubMed1984

Human renal allograft blood flow, oxygen extraction, and prostaglandin release: their bearing on graft function.

The intraoperative blood flow, oxygen extraction, and prostaglandin production were studied in 26 transplanted kidneys. Eleven were from related donors and 15 from cadavers. Postoperative dialysis was required by four of the five recipients of a cadaveric kidney having an intraoperative blood flow of less than 200 ml/min/100 gm of tissue. All the cadaveric kidneys with a blood flow greater than this produced urine immediately after revascularization. The blood flow in the cadaveric kidneys was related to the total ischemia time, with a lower rate in kidneys preserved for more than 24 hours. There was no difference in the oxygen extraction values for the kidneys in the related donors, in their associated recipients, and in the cadaveric organ recipients. During postoperative catheterization of the renal vein the oxygen extraction for the kidneys from related donors was practically normalized, while for the cadaveric kidneys it was increased though still subnormal. This difference was also reflected in the renal function at that time. No evidence was found that prostaglandins are involved in the regulation of the blood flow to the graft kidney.

Adolescent↗
PubMed1984

Deterioration in glucose metabolism in pancreatic transplant recipients after conversion from azathioprine to cyclosporine.

Six recipients of combined pancreas and kidney transplants displayed a deterioration in glucose tolerance when the immunosuppressive therapy was changed from azathioprine-prednisolone to cyclosporine-prednisolone. Because at the same time the plasma C-peptide level increased it seems that insulin resistance, rather than reduced insulin secretion, caused the impairment in glucose tolerance. The condition was found to be reversible.

Adult↗
PubMed1984

Optimal cyclosporine plasma levels decline with time of therapy.

To avoid nephrotoxicity and hepatotoxicity the CsA-PL should be kept at less than 500 ng/mL during the first month after transplantation and less than 200 ng/mL after four months. After ten months most patients in this study had a CsA-PL of less than 150 ng/mL and many had levels of less than 50 ng/mL with an apparently good immunosuppressive effect. Rejections showed no correlation with high or low CsA-PL. Continuous monitoring of CsA-PL is recommended for the management of renal allograft recipients.

Adolescent↗