Diagnosis of rejection in liver transplantation.
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Biomedical subjects
Publications and source records attributed to E Taskinen.
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To assess the effects of bevantolol on stable angina pectoris of effort and its impact on metabolic risk factors, a comparison study of this beta 1-blocking agent and atenolol was undertaken in 40 subjects (mean age 51 years). After a 4-week, single-blind, placebo washout period, 12 men and 8 women were randomized to receive 150 mg of bevantolol twice daily and 12 men and 8 women to treatment with 100 mg of atenolol once daily in a parallel, double-blind, 12-week treatment phase. Patients were assessed at weeks 2, 6 and 12 after bicycle exercise until angina or ST-segment depression greater than or equal to 0.15 mV appeared. Concentrations of cholesterol lipoproteins and 3 prostaglandin metabolites were determined. One patient receiving bevantolol was withdrawn from the study because of insufficient efficacy and 2 receiving atenolol were withdrawn because of side effects. After 2 weeks of therapy, significant decreases were seen in both groups in the number of angina attacks, mean sitting heart rate, systolic and diastolic blood pressure, mean maximum heart rate during exercise and mean double-product of systolic blood pressure and heart rate at the end of exercise. There was a trend toward significance in the increase of mean duration of exercise and total work performed with both agents, although these values were not statistically significant. Both high density lipoproteins and the ratio of high density lipoproteins to low density lipoproteins increased in the bevantolol group and decreased in the atenolol group. These changes were statistically significant at week 6.(ABSTRACT TRUNCATED AT 250 WORDS)
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The condition called "lactation optic neuritis" has been previously considered a clinical entity of its own. Four women, who developed optic neuritis within 1-12 months while breast-feeding their infants, were investigated ophthalmologically and neurologically in order, to find specific clinical features for this condition. The course of the disorder was similar to classic optic neuritis without lactation. The clinical history and laboratory findings in three of the four patients suggested a demyelinating disorder. It is possible that the decreased immunosuppressive activity just after pregnancy induces the manifestation of an underlying demyelinating disease. The existence of "lactation optic neuritis," however, is questioned as a separate entity of its own. Lactation together with decreased immunosuppression may merely act as a provocateur in the onset of optic neuritis, which in many cases is the first clinical manifestation of incipient multiple sclerosis.
Forty-six patients with juvenile autoimmune thyroiditis were followed for an average of 6.5 years. The diagnosis was based on a firm goiter and on cytologic findings of lymphocytic thyroiditis. The thyroid function and the size of the thyroid gland were regularly evaluated, and thyroid cytologic findings reevaluated once about 4.5 years after the diagnosis was made. Initially, 24 patients were euthyroid, 16 subclinically hypothyroid, and six hypothyroid. At the end of follow-up, 29 patients were euthyroid, six subclinically hypothyroid, and 11 hypothyroid, but there had been an extensive exchange of individual patients among these three groups. At cytologic reevaluation, the changes were virtually unaltered. Thyroid antibodies and circulating immune complexes were repeatedly tested: on one or more occasions, 85% of the patients had positive test results for thyroid antibodies, and about 50% for circulating immune complexes. Hypothyroidism at the end of follow-up correlated with the initial hypothyroid state and with thyroglobulin antibodies of IgG class detected by enzyme immunoassay. The best predictors of the final hypothyroid state were female sex, initial hypothyroidism, IgG thyroglobulin antibodies by EIA, and IgG circulating immune complexes assayed by conglutinin-binding test-EIA.
Monoclonal mouse antibodies to the "framework" determinants of the class I and II molecules of the major histocompatibility complex (MHC) were used to demonstrate the presence of the MHC antigens in human liver. First, the localization of these antigens was demonstrated from frozen section histology with indirect FITC immunofluorescence and the cell component(s) binding the mouse antibody were identified by rabbit marker antisera and indirect TRITC immunofluorescence. Second, the antigen expression on the cell surface was analyzed by the Staphylococcus aureus rosette method from cytological cell smears. All antibodies reacted with cells in the liver sinusoids, both with the Kupffer cells and at least partially with the sinusoidal endothelial cells. The same antisera reacted also with the bile duct cells, though weaker, and with some stromal cells in close proximity of the blood vessels. The vascular endothelial cells of hepatic artery, hepatic vein, and portal vein displayed no reaction. Thus human liver differs strikingly from, e.g., human kidney, where the vascular endothelial cells contain large amounts of MHC antigens on the cell surface. This difference may be one explanation to why liver allografts are less promptly rejected than renal allografts in man.
Alterations of cerebrospinal fluid (CFS) proteins and cells and blood-brain barrier impairment were determined in 4 patients with proven and 2 patients with presumptive herpes simplex virus encephalitis ( HSVE ) using simultaneous nephelometric measurements of CSF and serum albumin and immunoglobulins and combined MilliporeR filtration-cytocentrifuge cytologic techniques. The follow-up period ranged from 17 to 855 days. All patients showed intrathecal IgG synthesis which in 1 case continued for 28.5 months (855 days). The daily production of IgG in the central nervous system ranged up to 1157 mg. CSF-IgA and -IgM were also elevated in the early phase of the disease. The impairment of the blood-brain barrier was variable being apt to develop during the first 2 months of the disease and diminishing thereafter. Pleocytosis, mainly due to lymphoid cells, varied from slight to severe (325 X 10(3) cells/ml) and was observed in the CSF of all cases during the first 2 months. Lymphoid reaction (increase of enlarged stimulated lymphoid cells) was persistent and was the most pronounced cellular alteration. The lymphoid reaction and intrathecal IgG synthesis indicated continuous immunoactivation of the CNS, which was most intensive during the first 2 months and appeared to persist for at least 16-28.5 months.
We have analyzed the inflammatory changes in pig liver allografts and autografts by fine needle aspiration biopsy (FNAB) and correlated the cytological findings with transplant histology and changes in recipient blood. In nonimmunosuppressed piglets (n = 9) the inflammatory episode of rejection occurred promptly, peaked on days 4-7, and thereafter subsided in cases in which the graft was accepted (n = 6). The early inflammatory infiltrate consisted of all major types of inflammatory leukocytes, including T lymphoblasts, B plasmablasts, and plasma cells, lymphocytes and monocytes; macrophages dominated the late inflammatory lesion of irreversible rejection. In piglets that died of rejection (n = 3), the inflammation peaked earlier and the total amount of inflammation, including the frequency of blast cells and mononuclear phagocytes, was higher. These differences were, however, statistically insignificant and not predictive for irreversible rejection. In sham-operated autograft recipients (n = 5) no inflammation was recorded in the graft. Application of cyclosporine (n = 5), significantly suppressed the total inflammation (P = 0.02 and 0.06 on days 4 and 7, respectively) and delayed the peak; in addition, both the blastogenic component (P = 0.08 on day 4) and the mononuclear phagocyte component (P = 0.03 on day 7) were clearly suppressed. These inflammatory changes, recorded by the FNAB, had a close correlation with biopsy histology. On the other hand, determinations of S-ASAT, S-ALAT, and S-AFOS was not correlated with the episodes of rejection, and no characteristic changes were seen in blood cytology during the rejection episodes either.
A chronic pulmonary granulomatous reaction was associated with an almost identical clinical picture in two patients exposed to talc. In both patients lung biopsy showed the deposition of talc particles and a heavy granulomatous reaction. At the time of diagnosis the Kveim test result was negative in both patients, urinary calcium excretion was normal, and there were no extrapulmonary manifestations and no response to steroid treatment. These findings point against sarcoidosis. The serum angiotensin-converting enzyme level, however, was raised in both patients. It was concluded that the patient who was exposed to talc in the rubber industry had a true talc pneumoconiosis. The other patient, who was exposed to cosmetic talcum powder, suffered from chronic sarcoidosis with talc deposition in the lungs, since an enlarged axillar lymph node containing granulomatous inflammation was discovered after two years' follow up. These cases show that it may be extremely difficult to differentiate between chronic sarcoidosis and talc pneumoconiosis even after careful clinical and histological analysis.
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.
We have analysed retrospectively 100 consecutive patients with cryptogenic fibrosing alveolitis, who were treated with corticosteroids and followed for at least three years. At the time of diagnosis biopsy specimens were available in 64 cases. The clinical, radiographic, physiological, and histological features and the response to steroid treatment have been correlated with the prognosis. An early objective functional improvement was observed in 30%. Analysis of the survival data (life table and log rank test) showed a longer survival in younger patients and in patients with a shorter duration of symptoms before presentation, less radiographic abnormality, and less impairment of diffusing capacity, but not clearly in patients with more cellular histological appearances. The most favourable prognostic sign seemed to be an early response to steroid treatment.
Ninety-nine TruCut needle biopsies were performed on 92 patients with sarcoidosis. Non-caseating granulomas were found in 77 of 92 patients (84%) and in 78 of 99 biopsies (79%). Granulomas were found in 67% of patients showing only slight radiographic opacity (ILO classification grades 0/0-1/1) and in 90% of patients with higher radiographic grades (ILO 1/2-3/3). There was also a positive relationship between the size of the biopsy specimen and the presence of granulomas. Granulomas were found in 68% of small biopsy specimens and in 90% of moderate or large specimens.
The enzyme-linked immunosorbent assay (ELISA) was used to determine levels of specific IgG antibodies against measles, rubella, vaccinia, corona (OC43) and mumps viruses in cerebrospinal fluid (CSF) and serum of 18 patients with clinically definite multiple sclerosis (MS), 8 patients with optic neuritis (ON), 27 patients with other neurological disease (OND), and 88 control subjects without central nervous system disease. Serum antibody levels were not significantly different between the four groups. Differences in the frequency and levels of CSF antibodies between the four groups were observed. Control patients had serum/CSF antibody ratios from 2.0 to 3.0 (log) with an average of 2.5 corresponding to a 320-fold difference between serum and CSF antibody levels. MS patients had ratios from 1.1 to 2.1 with an average of 1.6. The average was 2.0 for the ON patients. The average for the OND patients was similar to the controls. The altered serum/CSF ratios for several viruses within an individual patient was similar. These results suggest that nonspecific immunostimulation is responsible for the increased levels of CSF virus antibodies.
Cerebrospinal fluid (CSF) cells and proteins were determined for 33 patients exposed to industrial organic solvents. A lymphoid reaction, i.e., a pathologically elevated number or percentage of enlarged lymphoid cells was observed in one-third of the patients, more often in patients with chronic intoxication (40%) than in those currently exposed to organic solvents (32%). An almost significant decrease of small lymphocytes in the CSF was observed among patients who had a past history of chronic solvent intoxication but no recent exposure. No cytological evidence of tissue destruction was found. Signs of slight blood--CSF barrier damage occurred in 5 (23%) of the currently exposed patients, but intrathecal IgG synthesis was not observed. Increased cellular activity in the CSF was also accentuated in principal component analysis. The results suggest slight nonspecific immunoactivation in the central nervous system of subjects exposed to organic solvents.
An unusual, severe pneumonia probably caused by varicella-zoster virus is reported in a 19-year-old previously healthy man. The diagnosis was based on high titer of varicella-zoster antibodies in serum, and demonstration of varicella-zoster antigen from lung biopsy specimen. The uncommon feature in the pathophysiological course of the disease was the selective hypercarbia that responded well to bronchodilator therapy with theophylline. Furthermore, the patient had no skin manifestations during his illness.
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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We studied CSF and serum samples from 16 patients with progressive myoclonus epilepsy (PME). These patients had juvenile-onset PME with evidence of autosomal recessive inheritance and no Lafora bodies. Twelve of the 16 patients with PME had immunologic abnormalities. Oligoclonal gamma bands were seen in six of the eight patients from whom sufficient CSF was available. The CSF albumin and serum/CSF albumin ratios were normal in all 16 patients, indicating the presence of intact blood-brain barriers. Six of the 16 patients showed increased CSF IgG levels and five had an increased CNS IgG synthesis. All patients had normal serum and CSF IgM and IgA levels. Three patients, all with bands, had reduced measles and/or vaccinia serum/CSF antibody ratios. The findings suggest altered immune response of the CNS of some patients with PME apparently caused by nonspecific immunostimulation.