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Biomedical subjects

J Ahonen

Publications and source records attributed to J Ahonen.

At least 181 records · Page 10Linked to original sources

Serum vitamin B12 concentration after proximal gastric vagotomy.

The serum concentration of vitamin B12, blood hemoglobin, and gastric acid secretion capacity was studied preoperatively and 1 and 5 years after proximal gastric vagotomy (PGV) in 15 patients. There was a significant reduction in the mean concentration of vitamin B12 at 1 year, but this disappeared within 5 years after PGV. The serum concentration of vitamin B12, however, remained at all times within the health-related reference interval. The blood hemoglobin concentration was unaltered during the follow-up period. The decrease in gastric acid secretion capacity gained by PGV was permanent, and no tendency to increased acidity was observed during the 5-year period. The temporary decrease in serum concentration of vitamin B12 reflects a PGV-induced diminished production of intrinsic factor in the parietal cells. In the characterization of parietal cell function the determination of serum vitamin B12 concentration is, however, much less sensitive than gastric acid secretion tests. The observed change in vitamin B12 concentration after PGV was subclinical, self-corrected, and thus required no treatment.

Adult↗

Cyclosporine in treatment of corticosteroid-resistant episodes of rejection.

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.

Adolescent↗

Serum amyloid A levels in human renal allograft rejection.

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.

Adult↗

Effect of cyclosporine on wound healing.

Two prophylactic immunosuppressive drugs, cyclosporine and methylprednisolone (MP), were compared for their effect on the in situ inflammatory reaction of granulation tissue formation and on wound healing. Granulation tissue was generated via implantation of viscous cellulose sponges in Sprague-Dawley rats. The rats were divided into six groups: One group received 40 mg/kg/day of cyclosporine, the second 10 mg/kg/day of cyclosporine, the third 2.5 mg/kg/day of cyclosporine, the fourth 12 mg/kg/day of MP, the fifth received the cyclosporine solvent, and the sixth group was given only saline. All drugs were given i.p. No reduction in the number of inflammatory cells was observed in the cyclosporine-treated sponges compared with the controls, whereas MP suppressed the inflammation strongly. Differential counts demonstrated a relative enrichment of macrophages in the cyclosporine-treated versus the MP-treated or control sponges. Chemical analyses of the sponge extracts agreed well with the cytological data: MP suppressed the total DNA content of the sponges, a marker of total cellularity, as well as the content of acid phosphatase and beta-glucuronidase, both markers of macrophages, but no such suppression was seen in the cyclosporine-treated sponges. The alkaline phosphatase content, a marker for granulocytes, was similar in all groups. A remarkable suppression in the contents of hydroxyproline, reflecting the amount of collagen, and in that of hemoglobin, reflecting the amount of neovascularization, was observed in the MP-treated sponges, whereas no such suppression--but possibly a slight enhancement of the second parameter--was observed in the cyclosporine-treated sponges. We conclude that, in contrast to MP, cyclosporine does not inhibit the inflammatory reaction of granulation tissue formation or the regenerative process of wound healing.

Acid Phosphatase↗

Ranitidine and cimetidine in renal transplantation: a clinical trial.

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.

Adult↗

Serum amyloid A protein: a sensitive indicator of renal allograft rejection in humans.

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.

Adult↗

Differential diagnosis of Cyclosporin A nephrotoxicity versus rejection by fine needle aspiration biopsy.

Twelve transplants with signs of graft failure and five with good function on CyA, were aspiration biopsied and analysed for (a) the presence of inflammation, (b) morphological changes in the graft parenchymal cells and (c) by indirect immunofluorescence for the presence of CyA in the renal tubular cells. Four reaction patterns were recorded: (i) good transplants with a normal serum creatinine, no evidence of inflammation, no parenchymal cell changes and no deposits of CyA in the graft; (ii) patients with elevated serum creatinine, no inflammation but distinct parenchymal cell changes and massive deposits of CyA (i.e., nephrotoxicity); (iii) patients with elevated serum creatinine, distinct inflammation in situ, modest tubular cell changes and no CyA in the graft (i.e., rejection); and (iv) patients with elevated serum creatinine, distinct inflammation in situ, distinct tubular cell changes and concomitant deposits of CyA (i.e., nephrotoxicity and rejection). CyA deposits in the graft had only a marginal relationship to drug dose and concentration of the drug in serum. When the dose was reduced, the deposits rapidly disappeared and tubular cell changes resolved. We recommend the FNAB for differentiating between nephrotoxicity and rejection in renal transplants.

Biopsy, Needle↗

Connective tissue changes and collagen metabolism in syngeneic vena caval grafts in rats.

An attempt was made to determine if changes occurring in connective tissue and collagen metabolism of vein-to-artery grafts arose from the trauma of transplantation as such or from the higher pulsatile pressure. Segments of the supradiaphragmatic inferior vena cava were therefore transplanted to the infrarenal vena cava in syngeneic pairs of rats. The sequential changes in hydroxyproline concentration, 3H-proline incorporation and the histologic appearance of collagen, elastic fibres and fibronectin were noted. Comparisons were made with previously reported changes in syngeneic venoartery grafts in rats. The initial changes, probably resulting from the transplantation trauma, were similar in the veno-vein and veno-artery grafts. Subsequent changes, however, were less pronounced in veno-vein than in veno-artery grafts. The study thus suggests that these changes in vein-to-artery grafts are due partly to the transplantation trauma, but mainly to the increased pressure in the new environment.

Animals↗

Five-year results of proximal gastric vagotomy.

Between February 1972 and December 1976 100 proximal gastric vagotomies (PGV) were performed on duodenal ulcer patients after failure of conservative treatment. The diagnosis was verified by preoperative barium meal and endoscopy and by peroperative examination. There was no operative mortality. Mean duration of postoperative hospital stay was 9.6 days. The percentual distribution in Visick-grading at the 1-year follow-up was 90% in class I + II, and 10% in class III + IV. The corresponding figures at the 5-year follow-up were 82% and 18%. The mean postoperative basal acid output did not change from one to five years. The reduction in pentagastrin stimulated acid output was unchanged at the 1- and 5-year follow-up. Neither did the mean acid output after insulin stimulation change between one and five years postoperatively. The mean concentration of serum gastrin was raised at one year but decreased to normal at the 5-year follow-up. Ten patients (10%) had ulcer recurrence during follow-up. Seven of these were successfully treated by gastric resection and three by antacids and cimetidine.

Adult↗

Gastric blood flow, tissue gas tension and microvascular changes during hemorrhage-induced stress ulceration in the pig.

Various features of blood supply to the gastric mucosa were studied in the piglet stomach during stress ulceration induced by hemorrhagic shock. Gastric blood flow, as measured by the radioactive microsphere technique, significantly decreased during shock, but no major change occurred in the gastric function of total cardiac output. There was no difference in the magnitude of the decrease of mucosal blood flow between the nonulcerating antral mucosa and the more readily ulcerating corpus or fundic mucosa. At the same time, a significant decrease in tissue partial pressure of oxygen and increase in tissue partial pressure of carbon dioxide occurred, but again no difference was observed between the antrum and the corpus. Microangiographic studies demonstrated a clearly diminished filling of the arterial and capillary bed of the gastric mucosa during shock, suggesting intense vasoconstriction, thrombosis of the mucosal blood vessels, or both. These changes were more prominent in the corpus portion of the stomach than in the antrum. At the site of mucosal lesions, the filling defects persisted even after the shock, suggesting permanent thrombosis of the blood vessels.

Angiography↗

The desmoid tumor. III. A biochemical and genetic analysis.

We have carefully examined four patients with desmoid tumor (DT) and their 31 relatives. In three of four cases, biopsies of the DT demonstrated low yet significant amounts of estrogen but not progesterone receptors in the tumor cytosol. In the fourth case, where the receptors were not demonstrable, the affected patient was a menopausal woman and the receptors may have been blocked by endogenous estrogen. Fourteen of their 31 relatives demonstrated multiple minor bone malformations in x-ray screening of the skeleton. The inheritance of these malformations was compatible with an autosomal dominant trait with variable penetrance. These findings are compatible with our suggestion that the basic underlying cause for DT is an inherited defect in growth regulation of the connective tissue. When a trauma is superimposed on such an individual, a DT may result. The growth of the tumor is, however, controlled primarily by sex hormones, estrogen predominance over progesterone being inducive to tumor growth.

Abnormalities, Multiple↗

Is uremia immunosuppressive in renal transplantation?

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.

Adult↗

Varying course of hypertension following renal trauma.

Hypertension developed in 5 patients after unilateral renal injury. The time-lag from injury to development of hypertension varied from 6 weeks to more than 3 years. In 2 of 3 patients with partial renal injury blood pressure normalized spontaneously. In the third patient sustained hypertension was cured by nephrectomy 56 months after injury. Nephrectomy led to normotension in the 2 patients with renal artery thrombosis, in 1 of them 14 years after renal trauma. Activation of the renin aldosterone axis was observed in all patients. The causes of varying time-lag from renal injury to onset of hypertension are obscure. Because of possible spontaneous regression of hypertension sufficient followup is recommended in patients with a history of renal injury. On the other hand, nephrectomy may be curative even after long-standing hypertension caused by traumatic renal artery thrombosis.

Adolescent↗

Are transplantation antigens stable constituents on human renal allografts?

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.

Animals↗