Biomedical subjects
Publications and source records attributed to B Eklund.
We have analyzed one human liver transplant by frequent FNABs. We conclude that FNABs of liver transplant recipients is a safe procedure that can be performed repeatedly without danger to the graft or to the graft recipient. The inflammatory episodes of rejection may be recorded and certain changes in the transplant--in particular, cholestasis and deposits of CsA--may be demonstrated in the FNAB as well.
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We used cyclosporine (formerly called cyclosporin A) to treat established episodes of kidney-transplant rejection in six patients in whom the use of corticosteroids either was ineffective or was precluded by preestablished side effects. All patients were followed up by using fine-needle aspiration biopsy and transplant aspiration cytology. In four episodes of rejection with typical blast cell--dominated inflammation, the response to cyclosporine was apparently favorable: the inflammatory cells disappeared within days and the transplant resumed its normal function. One episode of acute rejection was overcome within a week after discontinuing treatment with cyclosporine. In one episode of chronic rejection that was devoid of any distinct blastogenic component, no effect of cyclosporine could be detected. We believe that cyclosporine can be used to treat established episodes of rejection, but what type or types of inflammatory episodes are susceptible to cyclosporine must first be clarified through prerandomized clinical trials.
Serum amyloid A (SAA) levels were studied in 35 recipients of cadaveric renal transplants. Marked SAA elevations were seen during all acute allograft rejection episodes. The mean peak SAA level in well-documented rejections was 446 mg/l (median 415 mg/l, range 132-1040 mg/l; controls less than 1 mg/l). Rejections in patients receiving cyclosporin-A alone as post-transplantation immunosuppressive medication were characterized by a significantly higher peak SAA level than rejections in patients receiving cyclosporin-A in combination with methylprednisolone (539 +/- 53 mg/l, mean +/- SEM, vs 226 +/- 9 mg/l, P less than 0.01). Excluding surgery-induced SAA elevations in the immediate postoperative period, seven significant SAA peaks not related to allograft rejection were observed. These were associated with surgical complications and infections, and in one case probably with the underlying rheumatic disease, which was complicated by amyloidosis. The results show that acute renal allograft rejection induces a dramatic acute phase SAA response. Since SAA is an easily measured serum component and the rejection-induced elevation is an early event, monitoring of SAA in kidney transplant patients may have considerable clinical significance.
Intramuscular pressures were measured in the anterior tibial and deep posterior muscle compartments in eight healthy individuals before, during, and after short-term exercise and in 38 individuals after long-term exercise by the wick catheter method. Muscle biopsies were also taken and analyzed for muscle fiber distribution, water content, and lactate content. There were no elevations of the intramuscular pressures in the anterior tibial and the deep posterior muscle compartments after exercise nor was there any evidence of edema or anaerobic metabolism in the muscles examined.
1,25-Dihydroxycholecalciferol (1,25-DHCC) was administered to four patients on maintenance hemodialysis and to four patients with renal failure not requiring hemodialysis. Secondary hyperparathyroidism was found in both groups of patients. Before initiation of 1,25-DHCC treatment both groups had serum 1,25-DHCC levels below the normal range (33.1 +/- 15.3 pg/ml). During the treatment period, serum 1,25-DHCC concentrations were normalized. Parathormone concentration in serum decreased in both groups during the observation period. Serum calcium concentration was normalized in patients with renal failure and within the upper normal range in patients on maintenance hemodialysis. Bone biopsy and densitometry, of the radius showed a trend towards normalization of bone during the treatment period, while X-ray studies showed no clear effect of 1,25-DHCC treatment. This study shows that changes in bone mineralization can be reversed by normalization of 1,25-DHCC.
Sixteen patients were randomized for treatment with ranitidine and seventeen for treatment with cimetidine to prevent the appearance of upper gastrointestinal (UGI) complications after renal transplantation. The two operated groups were comparable with regard to age, sex, number of pre-operative blood transfusions, and HLA match. All patients were treated with a similar immunosuppressive regime, consisting of azathioprine and methylprednisolone, and underwent endoscopic examination ten and thirty days following surgery. In the second endoscopy an entirely normal condition was observed in 11 and 12 cases in the oesophagus, 4 and 4 cases in the stomach and 13 and 12 cases in the duodenum in the two groups of 16 and 17 patients respectively. Except for one uncomplicated prepyloric ulcer in the cimetidine group, the remaining endoscopic findings were mild in intensity. There were, however, significantly more rejection episodes in the cimetidine group than in the ranitidine group. Ranitidine seems to be a safe drug in transplant patients, but the high incidence of rejection episodes in the cimetidine group is a cause for concern.
Acute human renal allograft rejection induces a dramatic elevation of serum amyloid A protein (SAA). To evaluate the clinical significance of this finding we monitored 31 consecutive recipients of cadaveric renal allografts by daily SAA measurements. SAA increased significantly during 37/38 rejection episodes. Mean peak SAA level during the reversible rejections was 271 +/- 31 mg/L (SE, median 220 mg/L, n = 35) and during the irreversible rejections 680 +/- 29 mg/L (median 705 mg/L, n = 3). Excluding the predictable operation-induced SAA elevations that peaked on the second post-operative day, there were seven out of 42 SAA elevations (greater than or equal to 100 mg/L) not due to rejection. They were all caused by severe infections, and in one instance by a surgical complication. In 17 of the 35 SAA-positive rejections the SAA elevation (greater than or equal to 100 mg/L) preceded the clinical diagnosis by 1-5 days; in 11 it occurred on the same day; and in 7 one day later. Rejection episodes in recipients with initially nonfunctioning grafts were all also characterized by significant SAA elevations. We conclude that daily monitoring of SAA concentrations offers a valuable aid in the early diagnosis of acute allograft rejection. The SAA test is not a renal function test, so it can also be carried out in transplant patients who are anuric or oliguric in the postgrafting stage.
We have quantitated the impact of post-transplantation uremia on the antiallograft immune response by transplant aspiration cytology. Sixty-four consecutive renal transplants, treated with a similar immunosuppresive regimen, were aspiration biopsied at 2-day intervals during the first 15 days postoperatively. The patients were allocated into three groups on the basis of their serum creatinine level on the 3rd postoperative day: transplants with a delayed onset of function (highly uremic group, serum creatinine level greater than or equal to 600 mumol/liter; 24 cases), transplants with a partially delayed onset of function (partially uremic group, 200 to 600 mumol/liter; 21 cases), and transplants with an immediate onset of function (nonuremic group, less than or equal to 200 mumol/liter; 14 cases). These three groups were comparable in respect to the mean age, sex ratio, number of HLA-ABC mismatches (DR was not typed), number of pretransplant blood transfusions, and underlying diseases. Seventy percent of the transplants in the high uremic group, 60% in the moderately uremic group, and 60% in the nonuremic group underwent an early inflammatory episode during days 0 to 15 post-transplantation. The date of onset of inflammation was not significantly different in the three groups. However, the size and type of inflammation were significantly different: compared with the transplants in nonuremic patients, the total inflammatory response was slightly (P = 0.272) depressed in the transplants of moderately uremic patients and significantly (P = 0.007) depressed in the transplants of highly uremic patients. This depression was attributable to the depression of the blastogenic response: compared with nonuremic patients the blastogenic response was distinctly (P = 0.059) depressed in the moderately uremic group and significantly (P = 0.003) depressed in the highly uremic group. Instead, the frequency of in situ macrophages was the same in the three groups, or moderately elevated in the highly uremic group (P = 0.079). However, the graft survival was only 40% in the highly uremic group compared with 79% in the nonuremic controls and 81% in the moderately uremic patients (P = 0.016). We conclude that post-transplantation uremia partially impairs the antiallograft immune response, but this impairment is so small that other factors, whose nature cannot be explained on the basis of the present results, overrule the effects of uremia on graft survival.
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Hypertriglyceridaemia (HTG) may be caused by increased production or decreased removal of very low density lipoproteins (VLDL)or by a combination of these mechanisms. A decreased lipoproteinlipase activity (LLA) in the vascular wall of the tissues could be the mechanism of impaired removal. Therefore, the release of lipase activity from the forearm musculature after regional arterial injection of heparin was studied in healthy volunteers and patients with HTG. Heparin was injected in the doses 1.5, 15 and 150 i.u. and arterial and deep venous blood was sampled simultaneously at short intervals and analysed for LLA using intralipid with triple 14C-oleate as substrate. There was no significant difference in release of lipolytic activity between the groups and there was no significant correlation between plasma triglyceride concentration and LLA release in the HTG group or the whole material. Thus, deficient skeletal muscle LLA does not seem to be a general causative mechanism in HTG.
The reproducibility of pain limited exercise time (ET) and heart rate (HR) have been evaluated in repeated treadmill exercise tests in 24 patients with arterial occlusive disease of the lower limbs and intermittent claudication. The protocol includes a walking speed of 1 m/s and load increments of 10 watt/min and the two tests were separated by 1--14 days. The total ET was systematically increased by about 30 sec (P less than 0.05) at the second exercise test. The reproducibility of ET at the onset of leg pains was 34%, whereas the corresponding value at maximal leg pain was 16%. HR at the termination of the test did not differ systematically between the two tests and the reproducibility of HR was 6.1% and 5.5% at the onset of pain and maximal pain, respectively. It is concluded that a slight improvement in walking capacity at a second exercise test must be taken into account when evaluating different types of therapy in patients with intermittent claudication and, furthermore, that ET, walking distance or work load, should preferably be evaluated at or near maximal leg pain.
1. The influence of a fixed heart rate and cardiac output on the cardiovascular response to isometric handgrip at one third of maximal voluntary contraction has been studied by means of atrial pacing. 2. At rest, atrial pacing with a mean heart rate of 109 beats/min increased cardiac output and forearm blood flow while total systemic and forearm vascular resistance decreased. 3. During handgrip, total systemic resistance increased both with and without pacing. A slow lowering of forearm vascular resistance was noted in the former situation, no change in the latter. 4. It is concluded that atrial pacing per se increases cardiac output in healthy, young volunteers. Handgrip elicits a vasoconstriction on other vascular beds than the resting forearm.
The majority of cadaveric kidney transplants suffer at most one rejection episode, thereafter the postoperative course is usually uneventful. The remaining transplants have repeated rejections terminating often in prolonged irreversible rejection and transplant removal. We have been curious about this difference and analysed whether the two types of grafts display equally the major histocompatibility (MHC) antigens on their surface. Using monospecific rabbit antisera to HLA-ABC and -DR and/or alloantisera directed to allelic determinants of HLA-A and -B, we were unable to demonstrate the MHC antigens in most of the 'well-functioning' kidneys whereas these antigens were almost regularly present on the vascular endothelial cells of transplants with repeated and irreversible rejections.
A series of 143 living donor nephrectomies during a 14 year period is presented. The overall complication rate was 16 per cent. The incidence of wound complications was 4.2 per cent and of lower urinary tract infections 9.8 per cent. To date no donor has had known significant problem related to the nephrectomy or to the solitary kidney status.
We have performed fine-needle aspiration biopsies to well-to-do and repeatedly rejecting renal allografts. After biopsy the aspirated cells were treated either (a) with monospecific rabbit antisera to HLA-ABC, -DR or beta 2m, or (b) with ordinary anti-HLA-A and B alloantisera. After wash, the cell-bound antibody was chased with Staphylococcus aureus Cowan I bacteria and the antibody-binding cell type(s) was analyzed from stained cytocentrifuged cell smears. In normal, non-transplanted human kidneys the passenger leukocytes and (part of) the endothelial cells bound strongly both anti-HLA-ABC and -DR, the tubular cells weakly anti-ABC but not anti-DR while the glomerular cells did not bind either type of antiserum or bound them only very weakly. In 7 or 8 transplants with an excellent postoperative course we were unable to demonstrate the HLA-ABC and DR antigens on the graft endothelial component. Instead, in 7 of 8 transplants with repeated late rejection episodes, both the HLA-ABC and DR antigens were distinctly expressed on the endothelial cells of the graft.