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Biomedical subjects

A Nemlander

Publications and source records attributed to A Nemlander.

At least 19 recordsLinked to original sources
PubMed1997

Heart transplantation in Finland 1985-1995.

BACKGROUND AND AIMS: Since improved immunosuppression in the 1980's, heart transplantation is a well established procedure to treat patients with end-stage heart failure. The first heart transplantation in Finland was performed in 1985. Since then the activity has gradually increased to a level of about 25 annual transplants. The aim of this report is to sum up the clinical experience during the first 11 years. MATERIALS AND METHODS: From February 1985 till the end of 1995, 190 heart transplantations were performed in our institution. There were 176 males and 14 females ranging from 15 to 62 (mean 42.2) years of age. End-stage preoperative cardiac disease was dilating cardiomyopathy in 108 cases, coronary artery disease in 65 cases, valvular disease in 12 cases and congenital heart disease in five cases. RESULTS: The 30-day hospital mortality was 29 out of 190 (15.2%). The actuarial survival was 77% at one year, 75% at two years and 73% at 10 years. The most common causes of death were rejection (11 cases), graft failure (11 cases), abdominal complications (six cases) and cytomegalovirus (CMV) infection (four cases). A total of 87 rejection episodes occurred in 53 patients consisting 28 per cent of patients. 44 rejections occurred within three months post transplantation. Significant infections were noted in 198 instances in 97 patients. These were of bacterial origin in 92, viral in 48, fungal in 12 and protozoal in 10 cases, and 36 such infections which responded to antibiotics favourably but in which the microbe remained unidentified. 138 infections (i.e. 80%) occurred within 6 months post transplantation. In viral infections cytomegalovirus (CMV) predominated (29 out of 48). The CMV infection was significantly milder in patients who were seropositive preoperatively than in preoperatively seronegative patients with seropositive donors. CMV infection was associated with increased risk of post-transplant coronary artery disease. Three years after transplantation some restoration of sympathetic nervous response was observed at orthostatic test in heart rate and blood pressure. CONCLUSIONS: It can be concluded that 1) if a patient survives the three immediate postoperative months, his prognosis is good for the forthcoming years, 2) clinically significant rejections occur in less than one third of the patients, 3) cytomegalovirus is the most harmful agent post transplantation and a risk factor for post-transplant coronary artery disease and that 4) some restoration of sympathetic nervous control of the heart occurs within three years after transplantation.

Adult↗
PubMed1995

Barrett's oesophagus and perforation of gastric tube ulceration into the pericardium: a late complication after reconstruction of oesophageal atresia.

15 years after replacement of atretic segment with a gastric tube, perforation of an intrathoracic gastric tube ulcer into the pericardium, oesophago-pericardial fistula and severe mediastinitis developed in a 17-year-old male after reconstruction of oesophageal atresia using a retrosternal Heimlich-tube with a cervical oesophagogastric anastomosis. For six years he suffered from reflux oesophagitis and had Barrett's metaplasia in the cervical oesophagus. The patient had previously had one unsuccessful attempt to correct the oesophageal atresia at the age of two years using transverse colon. The two stage treatment included subtotal oesophagectomy, pericardiotomy, cervical oesophagostomy, gastrostomy, mediastinal and pericardial irrigation with antibiotics. After healing of the mediastinitis, the continuity of the alimentary tract was restored by using an isoperistaltic subcutaneous ileocolic segment. After a follow-up of five years the patient is well, without any oesophageal symptoms.

Adolescent↗
PubMed1993

Thoracoscopic fundoplication.

Thoracoscopic fundoplication and hiatoplasty were performed by a videoassisted technique in a patient with longstanding pathologic gastro-oesophageal reflux, reflux oesophagitis and hiatal hernia. Ten months later the patient was asymptomatic and had normal findings by oesophageal endoscopy and 24-hour pH-monitoring. Thoracoscopic fundoplication may be useful in patients with intra-abdominal adhesions due to previous abdominal surgery. Also obese patients with large hiatal hernias and perioesophageal adhesions may benefit from the thoracoscopic approach.

Adult↗
PubMed1990

The frequency of B cells secreting antibodies against donor MHC antigens in rats rejecting renal allografts.

We have estimated the frequency of B cells secreting antibodies against donor MHC antigens in rats rejecting histoincompatible renal allografts. In a major plus minor antigen-incompatible DA-to-WF combination on day 4 post-transplantation, reverse protein A plaque assay demonstrated that in the graft the frequency of lymphoid cells secreting Ig was 1:850. A major locus-incompatible and minor locus-compatible, congeneic LBN-to-Lewis strain combination was then applied to estimate the specificity of the secreted antibody. The lymphoid inflammatory cells were fused with mouse myeloma cells, cultured under limiting dilution conditions, and assayed by ELISA to donor and irrelevant strain spleen cells. Among cells infiltrating the graft, the fusion frequency was 1:172 x 10(3) and the frequency of Ig-producing hybrids 1:400 x 10(3) (i.e., this assay was approximately three log orders less sensitive than the reverse pA assay). The frequency of hybridomas secreting specifics antibodies against donor MHC antigens was 1:720 x 10(3) (i.e., every second hybridoma deriving from inflammatory population produced specific Ig). In addition, there was at least one obviously polyspecific population of hybridomas, detectable only in the spleen and reactive with all rat strains tested with a frequency of 1:700 x 10(3). The inflammatory cells were also cultured directly under limiting dilution conditions, and the frequency of Ig-secreting cells was determined by ELISA. The frequency of inflammatory lymphocytes secreting detectable amounts of immunoglobulin in the supernatant was 1:14 x 10(3) in the graft (i.e., this assay was approximately one log order less sensitive than the reverse protein A plaque assay).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Evidence that thymectomized, bone marrow-reconstituted rats do not reject their allografts.

We have investigated the reasons why thymectomized, bone marrow-reconstituted (B) rats do not reject their allografts, by comparing the structure of inflammation and functions of inflammatory cells in nonrejecting allografts to rejecting allografts in normal control recipients. The results demonstrate that B recipients mount a specific cellular response towards the graft. The response in B recipients differs from that in normal controls by a smaller intensity of inflammation, fewer blast cells, and activated mononuclear phagocytes in the inflammatory infiltrate, as well as a delay in the appearance of specific donor-directed lytic activity in the graft. B rats also have fewer blast cells and an inverted CD4/8 ratio in the spleen. There is no obvious absence of any given cell type or cellular function in the graft inflammatory infiltrate. In light of these results no cell type responsible for allograft nonrejection can be pinpointed.

Animals↗
PubMed1984

In situ effector pathways of allograft destruction. 3. Plasminogen activator activity in rat renal allografts.

The question of which cell components in a rejecting rat renal allograft secrete plasminogen activator (PA) has been analyzed. Although normal renal parenchymal cells also secreted PA, most of the PA in a renal allograft (and to a lesser extent also in an autograft) was produced by the inflammatory leukocytes. Fractionation at 1 g demonstrated that the inflammatory cell population responsible for the PA production in the allograft sedimented together with the large mononuclear phagocytes (macrophages). Fractions purified for small blast cells and large lymphocytes did not contain any PA activity but they were able to induce resting peritoneal macrophages to produce PA when cocultured in vitro. The results demonstrate that the allograft-infiltrating mononuclear phagocytes are "activated" in the sense that they secrete PA and that the activation of mononuclear phagocytes at the site of inflammation may be partially regulated by the inflammatory lymphoid cells.

Animals↗
PubMed1984

In situ effector pathways of allograft destruction. 1. Generation of the "cellular" effector response in the graft and the graft recipient.

Inflammatory leukocytes of DA-to-WF rat renal allografts displayed significant cytolytic activity to natural killer (NK) target cells on Day 2 after transplantation. The NK activity, which was associated with large granular lymphocytes in discontinuous Percoll gradients, peaked on Day 4 and disappeared rapidly thereafter. Coincident with the presence of NK activity in the graft, a decrease in NK activity in the recipient spleen was observed. Low NK activity was also recorded in WF-to-WF autografts. The cells displaying direct cytotoxic activity to donor (but not to recipient) strain peritoneal exudate target cells (PEC) were associated with the T suppressor/killer lymphocytes in affinity chromatography. They appeared in the graft between Days 2 and 4, peaked between Days 6 and 8 and disappeared slowly thereafter. In the spleen the cytotoxic T lymphocyte (CTL) activity appeared later and it reached a maximum between Days 16 and 20 before decreasing. In the blood distinct CTL activity was seen only from Days 16-20 onwards, after the graft had been rejected. No CTL activity was recorded in the graft, blood, or spleen of an autograft recipient. Addition of donor-directed post-transplantation antibody (antibody-dependent cellular cytotoxicity, ADCC) had a slight enhancing effect on the cytotoxic activity of inflammatory leukocytes up to Day 5. After this time, added antibody had a blocking effect on direct CTL activity. No ADCC activity was recorded in the inflammatory population of an autograft. On the contrary, high levels of ADCC activity to donor strain PEC were recorded in the spleens of both autograft and allograft recipients throughout the period of follow-up. The results demonstrate that at least three cellular effector pathways exist in an allograft: a strong natural killer cell component, a strong cytotoxic T lymphocyte component, and (possibly) a weak cell component participating in an ADCC type of cytotoxicity.

Animals↗
PubMed1984

In situ effector pathways of allograft destruction. 2. Generation of the "humoral" response in the graft and the graft recipient.

The frequency of both immunoglobulin (Ig)-synthesizing and Ig-secreting B cells have been analyzed in DA-to-WF rat renal allografts (and in control WF-to-WF autografts). We have correlated the in situ B-cell responses with corresponding events in the central lymphatic system of the recipient. Intracellular IgM- and IgG-containing plasma cells appeared in an allograft (but not in an autograft) very shortly after the transplantation. The numbers of both cell types in situ was approximately equal, the highest numbers of each being found on Day 4 after transplantation. A similar early response was observed in the recipient's spleen, however, very few Ig-synthesizing cells were seen in the blood. Only a fraction of the Ig-synthesizing cells in the allograft were involved in immunoglobulin secretion. Thus, the recovery of IgG- and IgM-secreting cells from an allograft was 10 and 2% of intracellular IgG- and IgM-containing cells, respectively. It appears, therefore, that allograft-infiltrating Ig-synthesizing B cells either die or migrate elsewhere before secreting immunoglobulin. The B-cell response in the graft occurs very early and is disproportionally high when the very low frequency of B lymphocytes in the allograft is considered. The data provide no evidence for inflammatory B cells being an integral part of graft rejection. Indeed, the possibility remains that the inflammatory B-cell response observed during the rejection process represents a meaningless byproduct of the inflammatory response.

Animals↗
PubMed1983

Are "natural killer" cells involved in allograft rejection?

"Natural killer" (NK) effector cells and large granular lymphocytes (LGL) are found inside rat renal allografts during rejection. Their appearance in situ precedes the appearance of cytotoxic T lymphocytes, and concomitantly with their influx in the allograft, the NK activity and the LGL are depleted from the recipient spleen. This suggests that the NK effector cells and the LGL are involved in allograft rejection, although their role(s) among the other in situ inflammatory effector pathways remains to be clarified.

Animals↗
PubMed1983

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↗
PubMed1983

Effect of irradiation on rat renal transplant rejection.

Leucocytes were selectively eliminated either from a DA renal allograft or from a WF host by irradiation of either the host or the graft on different days after the transplantation. The recovery of inflammatory leucocytes and the generation of lymphoid killer cells--that is, the natural killer (NK) cells and the cytotoxic T lymphocytes (CTL)--were analysed separately in the two compartments. Early irradiation of the graft did not affect the recovery of leucocytes in either compartment. The NK activity was only slightly reduced in the graft but was distinctly reduced in the spleen. A delay in the generation of the CTL activity was observed in the spleen. Late irradiation of the graft reduced the recovery of leucocytes in both compartments. The disappearance of the NK activity increased in the graft but not in the spleen. The CTL activity in the spleen developed normally up to day 6, whereafter it declined. After selective irradiation of the host a fair number of leucocytes remained in the graft, compared with a nearly complete disappearance of leucocytes from the graft and blood. The NK and CTL activity declined rapidly in both compartments. The data demonstrate a bidirectional interdependence between the graft and the host during the rejection.

Animals↗
PubMed1982

Redistribution of renal allograft-responding leukocytes during rejection. II. Kinetics and specificity.

We investigated the traffic of allograft-responding leukocytes between the host and graft without handling of these cells in vitro. The blood flow between the host and graft was disconnected, the proliferating cells were labeled with [3H]thymidine selectively in the graft or in the host, the label was chased with cold thymidine, and the circulation was reestablished. The localization of labeled cells was quantitated by autoradiography. The first host-derived labeled cells appeared in the graft and graft-derived labeled cells in the host, already on the 1st d after transplantation. This was followed by an exponential increase in the labeled cell traffic in both directions. The peak of traffic was observed on day 4 after transplantation, whereafter the traffic rapidly declined and tapered off. This decline was not due to exhaustion of supply, as the labeled cells continued to proliferate in their original compartments, nor to a slowdown of blood circulation, which took place 2-3 d later. We consider the decline to indicate that the rejection has proceeded to a (irreversible) stage autonomous of the host lymphatic and hematopoietic system. During the exponential increase, nearly one-third of the graft-infiltrating inflammatory cells were replaced as a consequence of relocalization during each 18-h-period. All mononuclear white cell types, with the exception of granulocytes, participated in the traffic. Most lymphoid cells entrapped in the graft were descendents of recent cell divisions; most of the mononuclear phagocytes derived from a preexisting phagocyte pool. The entrapment of labeled leukocytes in a relevant graft was specific: when an allograft and an autograft were simultaneously transplanted, a more than 50-fold entrapment was observed in the allograft, compared with the autograft. Very few of the cells localized in irrelevant positions, such as the liver and lung, of the recipient.

Animals↗
PubMed1982

Effect of cyclosporin A on the in situ inflammatory response of rat renal allograft rejection.

The impact of cyclosporin A (CyA) on a normal kidney parenchyma and on the in situ inflammatory response of rejection was investigated in normal DA rats and after transplantation of DA renal allografts to Lewis recipients. In a normal, non-transplanted DA kidney more than 80 mg/kg/day of CyA induced light-microscopic changes in the distal tubular cells of the renal cortex and outer medulla. These changes were not accompanied by any visible inflammation and were directly proportional to the dose of the drug and to the duration of drug administration. Treatment of a transplant recipient with 40 mg/kg/day of CyA abolished or at least efficiently reduced the in situ inflammatory response of rejection both as analysed from tissue sections and as quantified from the recovery of inflammatory cells after enzymatic digestion. It also reduced efficiently not only the number of T and B blast cells of the inflammatory infiltrate but also the number of other inflammatory cells, such as in situ lymphocytes, monocytes, and macrophages, and abolished or at least reduced the generation of (T) killer cells in situ and in the recipient spleen. These effects were inversely proportional to the time elapsed between grafting and initiation of treatment: although a complete suppression of all three features was obtained if the drug treatment was initiated already on the day of transplantation, a significant reduction of these functions was still found if the treatment was initiated later when the blastogenic response was already underway.

Animals↗