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J Tollemar

Publications and source records attributed to J Tollemar.

At least 37 records · Page 2Linked to original sources

Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients. A randomized, placebo-controlled study.

Eighty-six consecutive liver transplant recipients were prospectively randomized in a double-blind, placebo-controlled antifungal prophylaxis study. Seventy-seven patients received 5 days of prophylaxis starting during the transplantation with either liposomal amphotericin B (AmBisome) 1 mg/kg/day or placebo. Among 40 AmBisome-treated patients, no invasive Candida infection was seen during the first month, compared with 5 invasive Candida albicans infections among 37 control patients (P < 0.05). Furthermore, 1 placebo patient experienced Aspergillus niger pneumonia. Thus, the overall incidence of invasive fungal infections was 0/40 (0%) in the AmBisome group versus 6/37 (16%) in the placebo group (P < 0.01). Patient survival at 30 days was 92% versus 94% for AmBisome- and placebo-treated patients, respectively. One patient experienced backache related to AmBisome infusion. Two patients had transient thrombocytopenia possibly caused by AmBisome treatment. AmBisome was otherwise well tolerated. The total cost for all antifungal drugs used in both groups was equal. However, prophylaxis with AmBisome was $5000 less expensive than treatment of proven invasive fungal infections among placebo patients.

Adolescent↗

Deep Candida infection in child liver transplant recipients: serological diagnosis and incidence.

Nineteen children who received 22 orthotopic liver grafts on 20 occasions were studied with regard to Candida infection. Serum samples were analysed to determine Candida, IgA, IgM and IgG antibodies and detect free C. albicans glucoprotein antigen. Five children (25%) had a confirmed deep C. albicans infection (DCI) during the first 2 weeks after transplantation. In all children with DCI, serology was positive, a median of 6 days (range 2-9 days) before Candida infection was verified by fungal culture, direct microscopy and/or autopsy. The positive predictive values for Candida IgG, IgM and IgA antibodies in children with DCI were 100%, 78% and 100%, respectively, and for free C. albicans antigen, 45%. Pathological titres of IgM and IgA antibodies against Candida before liver transplantation were present in three of four children who later developed a DCI and in no child without infection. In conclusion, regular screening by Candida serology is recommended both before and after liver transplantation.

Adolescent↗

Transplantation of porcine fetal pancreas to diabetic patients.

Transplantation of fetal porcine islet-like cell clusters (ICC) reverses diabetes in experimental animals. We have now transplanted porcine ICC to ten insulin-dependent diabetic kidney-transplant patients. All patients received standard immunosuppression and, at ICC transplantation, antithymocyte globulin or 15-deoxyspergualin. ICC were injected intraportally or placed under the kidney capsule of the renal graft. Four patients excreted small amounts of porcine C-peptide in urine for 200-400 days. In one renal-graft biopsy specimen, morphologically intact epithelial cells stained positively for insulin and glucagon in the subcapsular space. We conclude that porcine pancreatic endocrine tissue can survive in the human body.

Adult↗

Detection of Candida albicans DNA in serum by polymerase chain reaction.

Polymerase chain reaction (PCR) was applied in order to improve the diagnosis of disseminated candidosis. A nested PCR technique with 2 primer pairs was used to increase the sensitivity. We were able to detect Candida DNA in serum and tissue samples from experimentally infected mice as well as in serum samples from candidemia patients and patients with deep-seated Candida infection. Our PCR could detect as little as 1 pg Candida albicans DNA. The PCR method was more sensitive than culture in both the mouse experiments and the patients with deep candidosis (5/7 were PCR positive and 0/7 blood culture positive), and of similar sensitivity in candidemia patients (11/17 were 15/17 blood culture positive). The relatively short processing time of PCR, when compared with culturing, its sensitivity, as well as the possibility of using serum samples for analysis, all helped improve the diagnostics in deep-seated candidosis and candidemia.

Adult↗

Safety of liposomal amphotericin B (AmBisome) in 187 transplant recipients treated with cyclosporin.

The safety of AmBisome was evaluated in 187 transplant recipients treated for 197 episodes. Patients included 89 bone marrow transplant recipients, 64 liver transplant recipients, 20 renal transplant recipients and 14 recipients of combined organs. AmBisome was instituted for verified invasive fungal infection in 34 cases, suspected invasive fungal infections in 80 cases and as prophylaxis in 83 cases. AmBisome was given for a median of 11 days (range 1-112 days) with a maximum daily dose of 1.49 +/- 0.70 mg/kg/day (mean +/- SD). The total cumulative dose of AmBisome was 1.11 +/- 1.78 g (mean +/- SD). Side-effects definitely attributed to AmBisome therapy included low potassium (n = 3), low back pain (n = 3), dyspnoea (n = 2), allergic rash (n = 1), nausea and vomiting (n = 1), confusion (n = 1), rise in alkaline phosphatase (n = 1) and cholecystitis (n = 1) with an overall incidence of 13 of 197 (7%). AmBisome was discontinued due to side-effects in 6 (3%) of the cases. During AmBisome treatment the mean cyclosporin dose was 9.6 +/- 28.8 mg/kg/day. Compared to pre- and post-AmBisome therapy there was a significantly increased cyclosporin concentration in blood during AmBisome therapy. Side-effects with possible association to AmBisome therapy included low serum potassium (36%), increase in serum creatinine (31%), rise in alkaline phosphatases (26%) and fever (3%). The overall mean increase in serum creatinine was 20%. Other possible side-effects like headache, abdominal pain, rash, rise in bilirubin, cramps and pancreatitis was seen in single patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Nutritional status, muscle composition and plasma and muscle free amino acids in renal transplant patients.

To investigate the effects of renal transplantation (Rtx) on the nutritional status, muscle composition and the plasma and muscle free amino acid (AA) pattern, three groups of altogether 30 renal transplant patients (group I n = 10; 46 +/- 14 [SD] days after Trx), (group II n = 10; 13 +/- 2 months after Rtx) and (group III n = 10; 9 +/- 2 years after Rtx) underwent anthropometric measurements, blood sampling and percutaneous muscle biopsy. The immunosuppressive therapy consisted of prednisolone, azathioprine and cyclosporine-A. The results were compared with data from age-matched healthy subjects. Renal function was impaired in groups I, II and III. Serum albumin was decreased in groups I and II. The patients of group II had an increased percentage of body fat, triceps and subscapular skin folds and total sum of skinfolds. In group I the ratio alkaline-soluble protein (ASP) to DNA, which is a sensitive index of protein depletion on the cellular level, was decreased. Muscle magnesium content was decreased whereas the muscle DNA, sodium and chloride contents were increased. The mean plasma concentration of most essential AA (EAA) was essentially normal except phenylalanine which was increased in groups I and II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Detection of CMV-matrix pp65 antigen in leucocytes by immunofluorescence as a marker of CMV disease.

The finding that active cytomegalovirus (CMV) infection is associated with an increased mortality after organ transplantation and the introduction of successful antiviral treatment render more urgent the development of rapid and accurate diagnostic methods. Rapid immunodiagnosis of active CMV infection was investigated by means of immunofluorescence staining of leucocytes by monoclonal antibodies. Monoclonals directed against the matrix protein, pp65, and ClonabR monoclonal antibody, which has been claimed to be directed against immediate early antigens, were used. All monoclonal antibodies directed against the matrix protein reacted equally well in staining of polymorphonuclear cells. Monoclonals described by Gerna et al. [1991] and by Pereira et al. [1982] also reacted more clearly with mononuclear cells. One hundred fifty heparinized blood samples were collected monthly from 82 patients within 3 months after transplantation. In addition, 132 EDTA blood samples were tested in connection with suspected CMV infection. The latter approach gave a better agreement between antigen detection and virus isolation. There was a relationship between active CMV infection and the finding of antigen-positive leucocytes (P = 0.002, Fisher's exact test) found within 1 month of one another. When the number of antigen-positive cells was taken into account, a relationship to severe CMV disease was detected (P < 0.001, Fisher's exact test). The antigen test was positive at an early stage during the development of severe CMV disease. This rapid method is useful for following the disease process of CMV and in determining when to initiate antiviral treatment.

Antibodies, Monoclonal↗

Infections in human liver recipients: different patterns early and late after transplantation.

The first 49 consecutive patients who underwent orthotopic liver transplantation between 1984 and 1989 in our department were studied with regard to symptomatic and asymptomatic post-transplantation infections. The major infections carrying a risk of fatal outcome are presented. During the first 4 weeks, fungal and bacterial infections predominated, the percentages of patients affected being 27% and 35%, respectively. Eight patients (17%) suffered from bacterial septicemia, which in six cases was due to gram-negative micro-organisms. The bacterial septicemia was often associated with severe ischemic damage to the graft, rejection, or cholangitis. In addition, a concomitant invasive fungal infection supervened in seven out of eight septic patients, further aggravating the patients' condition. Seventeen of the 49 patients (35%) died after transplantation within 3.3 years. Infection was the cause of death in nine patients (18%), with bacterial septicemia and/or fungemia in eight of these. Cytomegalovirus (CMV) disease was the dominant cause of illness after the 1st month. While only 5 of the 49 patients developed CMV disease during the 1st month (10%), as many as 16 of the 40 recipients who survived beyond that time suffered from symptomatic CMV viremia (40%). CMV mismatching, i.e., the donation of a CMV-positive organ to a CMV-seronegative recipient, entailed the highest risk for CMV disease. Pneumocystis carinii pneumonia occurred within 4 months in 10% of the patients. The four liver recipients affected were among the 20 patients not receiving trimethoprim-sulfamethoxazole prophylaxis. None of the 28 patients who received this prophylaxis over a 12-month period developed this complication (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Randomized double-blind study of liposomal amphotericin B (Ambisome) prophylaxis of invasive fungal infections in bone marrow transplant recipients.

Invasive fungal infection is a problem in patients undergoing bone marrow transplantation (BMT). To determine if a liposomal formulation of amphotericin B (Ambisome) is safe and can prevent fungal infection we performed a placebo controlled double-blind randomized prophylactic trial. Study drug was administered from when neutrophil count had decreased to < 0.5 x 10(9)/l and was continued until neutrophils recovered to this level or an infection or toxicity end-point was reached. Thirty-six patients received 1 mg/kg/day of ambisome and 40 patients received placebo daily. There were no statistical differences in characteristics or clinical course between the two groups. Fungal colonization decreased in the ambisome group while it increased in the placebo group. By the end of prophylaxis 8 of 24 (33%) patients receiving ambisome were colonized compared with 18 of 29 (62%) placebo patients (p = 0.05). Five and 7 patients on ambisome or placebo, respectively, were withdrawn due to a presumed fungal infection (NS). There was no statistical reduction of autopsy-proven fungal infection. Proven fungal infection occurred in one patient receiving ambisome (C. guillermondi) compared with three patients receiving placebo (C. guillermondi, 2; C. albicans, 1). Ambisome was well tolerated at the dose of 1 mg/kg/day but in three patients allergic reactions were observed.

Adolescent↗

Injection of xenogeneic endocrine pancreatic tissue into the portal vein--effects on coagulation, liver function, and hepatic hemodynamics. A study in the pig-to-dog model.

The safety of injecting discordant xenogeneic fetal endocrine pancreatic tissue into the portal vein was studied in a pig-to-dog system. It was found that minced fetal porcine pancreas and fetal porcine isletlike cell clusters prepared by collagenase digestion and culture could be injected with only minor or no hepatic hemodynamic disturbances. Coagulation studies revealed a small increase in plasma fibrinopeptide A, but this increase could be prevented by heparinization of the recipient. There was no consumption of fibrinogen or platelets. In contrast, injection of minced adult porcine pancreas caused pronounced hepatic hemodynamic changes and marked coagulation abnormalities, indicating consumption coagulopathy. The present finding that fetal porcine pancreas can be injected intraportally without deleterious effects in dogs provides a foundation for the eventual clinical use of such material as treatment for insulin-dependent diabetes mellitus.

Animals↗