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Biomedical subjects

J Marrink

Publications and source records attributed to J Marrink.

At least 19 recordsLinked to original sources

Detection of recurrence in patients with clinical stage I nonseminomatous testicular germ cell tumors and consequences for further follow-up: a single-center 10-year experience.

PURPOSE: A wait-and-see policy for patients with stage I nonseminomatous testicular germ cell tumors (NSTGCT) was evaluated in a prospective study. The frequency and time of recurrence, detection of recurrence, and presence of unfavorable prognostic factors were investigated. PATIENTS AND METHODS: During the period 1982 to 1992, 154 patients with stage I NSTGCT (median age, 29 years) underwent orchidectomy and were monitored at follow-up evaluation with physical examinations, alfafetoprotein (AFP) and beta-human choriogonadotropin (hCG) levels, chest x-rays (CXR), and computed tomographic (CT) scans of the abdomen and chest. Multivariate logistic regression analyses were performed to identify prognostic factors. RESULTS: During a median follow-up period of 7 years (range, 2 to 12), recurrence was found in 42 patients (27.3%). All cases of recurrence were detected within 2 years, 90% in the first year after orchidectomy. In 29 patients (69.0%), recurrence was detected in the abdominal lymph nodes. Nine patients (21.4%) had metastases in the retroperitoneum and mediastinum and/or lungs, and four patients (9.6%) had metastases only in the mediastinum or lungs. The majority of recurrences (97.6%) were detected by tumor markers and CT scans. Recurrence was related to the presence of vascular invasion, embryonal carcinoma (E), elevated preoperative hCG level, and absence of mature teratoma (M). Only vascular invasion was an independent risk factor. After polychemotherapy treatment for recurrence, the survival rate for the total group was 98.7%. CONCLUSION: The wait-and-see policy is a reliable method for follow-up monitoring of patients with stage I NSTGCT. Even in patients with unfavorable prognostic factors, it is justified to await the possible appearance of metastases. For the future, it is recommended that CXR be omitted from the schedule, and it might be feasible to discontinue follow-up evaluations after 5 years.

Adolescent

Tissue polypeptide-specific antigen: a discriminative parameter between prostate cancer and benign prostatic hypertrophy.

The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer and in 40% of the patients who were in an inactive phase. For TPS these values were 6, 34 and 0%, respectively. The metastatic progression was biochemically mirrored by pronounced elevations of PSA and TPS. These data suggest that TPS might be a valuable adjunct in the diagnosis and follow-up of patients with prostate cancer, especially in differentiating benign from malignant deterioration of the disease.

Antigens, Neoplasm

Origin of raised maternal serum alpha-fetoprotein levels in second-trimester oligohydramnios.

Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with second-trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a normal amniotic fluid volume. This suggests that in oligohydramnios the origin of excess AFP in the maternal compartment is amniotic fluid. It is proposed that oligohydramnios and the associated raised maternal serum AFP levels are caused by damage of the fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic fluid to the decidual tissue and resorption in the maternal circulation.

Amniotic Fluid

Maternal serum alpha-fetoprotein levels and fetal outcome in early second-trimester oligohydramnios.

Early second-trimester oligohydramnios was associated with normal maternal serum alpha-fetoprotein (MSAFP) levels in nine out of 26 cases (35 per cent). Congenital malformations of the fetal urinary tract resulting in fetal anuria were present in nine cases; in seven of them, normal MSAFP levels were measured. In contrast, normal MSAFP levels were established in only 2 out of the 17 cases without fetal malformations. These data suggest that fetal urine is the major source of elevated AFP in the maternal compartment in early second-trimester oligohydramnios. This is further supported by the lack of any relationship between concentrations of MSAFP non-reactive with Concanavalin A, originating mainly from the yolk sac-derived amniotic fluid AFP pool, and the presence of fetal diuresis. Three out of 26 women had experienced early second-trimester oligohydramnios in a previous pregnancy, suggesting the existence of a recurrence risk for this condition.

Concanavalin A

Serum lactate dehydrogenase isoenzyme 1 activity in patients with testicular germ cell tumors correlates with the total number of copies of the short arm of chromosome 12 in the tumor.

The aim of our study was to assess the relationship between the serum lactate dehydrogenase isoenzyme 1 (S-LDH-1) activity in patients with testicular germ cell tumors and the number of copies of the short arm of chromosome 12 (12p) present in tumor. Twenty-seven adult patients with measurable tumor lesions were studied. Twenty-five had three or more copies of chromosome 12 per cell in the tumors. Nineteen had one or more copies of a specific chromosomal abnormality, an isochromosome of the short arm of chromosome 12, i(12p). Fourteen had increased S-LDH-1 levels. S-LDH-1 activity correlated significantly with the product of total tumor volume and the total number of copies of the short arm of chromosome 12 present per cell (total tumor 12p). We conclude that the total number of copies of the short arm of chromosome 12 in the tumors is most probably a factor contributing to the LDH-1 activity released from the tumors.

Adult

Anti-GM1 antibodies in patients with Guillain-Barré syndrome.

Anti-GM1 antibodies were measured in 22 patients with the Guillain-Barré syndrome (GBS) and compared with anti-GM1 antibody activity in patients with other neurological or immunological diseases and in normal subjects. Four out of 22 patients with GBS had raised IgM, IgG, or IgA anti-GM1 antibody activities. All four patients were tetraparetic with only minimal or no sensory deficit. Three of the patients had highly raised antibody activity and showed severe residual deficits, while of the remaining patients with GBS, only one remained severely affected. One patient had anti-GM1 antibodies specific for GM1, whereas the other three patients showed antibody activity with asialo-GM1 or GD1b. The presence of anti-GM1 antibodies may define a subgroup of patients with GBS who have a poor prognosis.

Adolescent

Complement activation and the production of inflammatory mediators during the treatment of severe sepsis in humans.

Sepsis or septic shock is frequently associated with activation of the complement system, coagulation and fibrinolytic changes and the release of several cytokines. In this study we analyzed the relation of complement activation to the inflammatory mediators, hemodynamic and biochemical parameters and severity of illness and outcome in 20 consecutive patients with clinically defined sepsis. Levels of C3a and C3d were elevated in 90% of the patients (median levels 0.19 mg/l and 8.6 mg/l respectively) in comparison to 14% and 42%, respectively of 7 patients with non-septic shock. Levels of C4 were decreased in only 1 of the 20 septic patients. Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, respectively (median levels 122 ng/l and 1300 U/ml) and were clearly interrelated (r = 0.67, p less than 0.01). C3a levels correlated with the APACHE II score (r = 0.57, p less than 0.05) and high C3a levels were associated with fatal outcome (p less than 0.05). C3a was also correlated inversely with mean arterial pressure (r = 0.50, p less than 0.01). Levels of complement C3a and C3d significantly correlated with levels of plasminogen activator inhibitor-1 (PAI) and correlated inversely with AT-III levels. We found no correlation between these complement products and leukocyte counts or lactate levels, nor was there a correlation between C3a or C3d and the cytokines TNF and IL-6. Levels of C3a and C3d did not decrease significantly during the first 24 h of treatment, in contrast to a clear decrease in IL-6 levels in all patients and a decrease in TNF in the surviving patients. TNF levels remained stable or increased in the non-survivors. We conclude that both the complement system and the cytokine system are involved in the pathogenesis of septic shock and may be involved in the development of some of the fatal complications like hypotension and disseminated intravascular coagulation.

Aged

TRA-1-60: a new serum marker in patients with germ-cell tumors.

TRA-1-60 is a monoclonal antibody (MAb) that recognizes a mucin-like antigenic determinant expressed on the surface of embryonal carcinoma (EC) progenitor cells. In order to determine whether this antigen is released into the serum of patients with a non-seminomatous germ-cell tumor (NSGCT), we developed a sensitive 2-step immunoenzymometric assay. Of 42 EC-positive NSGCT patients tested, 32 (76%) were found to release TRA-1-60-reactive antigen into their serum, in contrast to 1 positive finding in 10 EC-negative NSGCT patients. The marker was found in 67% (10/15) of the EC-positive patients who were negative for both AFP and HCG. Sera from seminoma patients did not contain elevated levels of the TRA-1-60 antigen. Therefore, we propose that the TRA-1-60 antigen is a useful additional serum marker for following the progress of NSGCT(EC+) patients.

Antigens, Neoplasm

Aggressive chemotherapy for acute leukaemia frequently causes intestinal protein leakage.

Cytostatic drugs are known to produce disturbances in intestinal absorption of carbohydrates. To further explore the gastrointestinal (GI) toxicity of cytostatic therapy, 37 patients with acute leukemia were investigated during and/or after remission induction courses by the use of the differential sugar absorption test (DSAT) and the intestinal clearance of alpha-1-antitrypsin (ClAAT). The ratio of the lactulose to the mannitol excretion in the urine was found abnormal in 44% of the tests. The ClAAT was increased in 74% of tests. The tests results differed considerably from patient to patient and depended on the chemotherapy course; correlation between the tests was low, probably indicating the unrelated pathophysiological processes were measured. After haematological regeneration, abnormal test results normalised. It is concluded that aggressive chemotherapy not only causes a reduction in the absorption of sugars, but commonly also protein leakage. These GI side-effects are reversible, and the application of both tests in combination provides a practical and reproducible method for investigation of GI toxicity in patients treated with cytostatic drugs.

Adolescent

Alpha-fetoprotein-lectin binding as a marker of tumour activity or liver damage.

To establish whether alpha-fetoprotein (AFP) produced in the early post-treatment phase of a patient with a germ cell tumour of the testis or the ovary originates from the tumour or is due to an underlying disturbance in liver function, the binding of AFP to concanavalin A (Con A) was investigated as a discriminative variable. A two-step assay is described that can distinguish the type of AFP produced at levels as low as 10 ng/ml. A Con A-binding ratio of 12-43% was found in the patients with disseminated germ cell tumours and in patients with AFP-positive gastrointestinal carcinomas. AFP from the liver gives ratios below 10%.

Biomarkers, Tumor

Complement activation during an active cytomegalovirus infection after renal transplantation: due to circulating immune complexes or alternative pathway activation?

In 32 patients with a renal allograft, serial determinations after transplantation were made of C3d, the stable conversion product of the complement factor C3, as well as serial measurements of the anaphylatoxin C3a des arg. Furthermore, serial determinations were made on the presence of circulating immune complexes using three different assays (C1q binding assay, polyethylene glycol precipitation test, and indirect granulocyte phagocytosis test). Twenty patients were studied during an active cytomegalovirus (CMV) infection, and 12 patients were studied during allograft rejection or during stable phase after renal transplantation. In 12 patients with a CMV infection serial measurements were made of AP50 (alternative pathway of complement). During an active CMV infection elevated C3d as well as elevated C3a des arg levels were found and not in the control group (P less than 0.01). In 8 out of the 12 patients tested, with CMV infection, a decreased hemolytic activity of the alternative pathway (AP50) was found, together with the elevated levels of C3d and C3a des arg. Serum C4 levels were normal or high during CMV infection. Furthermore, circulating immune complexes were found to be positive in 15 out of the 20 patients with a CMV infection (both primary and secondary infections), and in 2 out of 12 patients of the control group. The complement activation found in the CMV group was not related to the presence of circulating immune complex-like material, since complement activation was present in advance of the appearance of the immune complexes, suggesting that complement activation was not due to classical pathway activation by those complexes. We conclude that our data are consistent with complement activation and the formation of biologically active peptides like C3a des arg in patients with an active CMV infection. The decreased hemolytic activity of the alternative pathway (AP50) together with the normal or high C4 levels suggest involvement of the alternative pathway, although further studies of the alternative pathway of C are warranted to confirm this hypothesis.

Adolescent

Results of adjuvant surgery in patients with stage III and IV nonseminomatous testicular tumors after cisplatin-vinblastine-bleomycin chemotherapy.

From January 1978 to April 1983, 53 patients were treated with cisplatin-vinblastine-bleomycin chemotherapy because of advanced nonseminomatous testicular tumor (NSTT). After the chemotherapy, the serum tumor markers were back to normal in 41 patients, of whom 35 were eligible for surgical removal of the residual tumor. In four patients, vital tumor tissue was found in the residual tumor. Salvage chemotherapy resulted in complete remission. Residual mature teratoma was encountered after the chemotherapy in 15 of the 25 patients with a teratomatous component and in one of the ten patients without a teratomatous component in the primary tumor. On completion of the study, 38 of the 53 patients (72%) are still alive, with a median follow-up of 65 months. Subdivided by tumor volume, survival is found to amount to 92% for small-volume disease, 67% for large-volume disease, and 64% for very-large-volume disease. Six patients (11%) developed a recurrence in the course of the follow-up. Exploratory laparotomy after remission induction chemotherapy is necessary in all patients with a teratomatous component in the primary testicular tumor who have become tumor marker negative, irrespective of the roentgenographic findings of the retroperitoneum. Patients without a teratomatous component in the primary tumor should have exploratory laparotomy only in case of roentgenographic evidence of retroperitoneal residual tumor. A thoracotomy is needed only in the presence of roentgenographic evidence of pulmonary residual lesions.

Adolescent

Double cryoprecipitated factor VIII concentrate from heparinised plasma and its heat treatment.

In an attempt to implement the small pool concept in Factor VIII purification, cryoprecipitate derived from heparinised plasma was reprecipitated in the cold providing a factor VIII concentrate for freeze drying and heat treatment. There was considerable purification; only 1% of the original plasma proteins was left in the final product. Factor VIII:C concentration was about 19 IU/ml. Factor VIII related antigen (RAg) appeared heterogeneous, with a broad base and asymmetry on crossed immunoelectrophoresis. Fibrinogen content was 15 g/l. In contrast to high-purity commercial concentrates, fibronectin was considerably concentrated. Immunoglobulin contents were similar to a high-purity commercial product. The amount of other plasma proteins was very small, varying from less than 0.2% for C3 complement to 2.3% ceruloplasmin. In some respects the preparation may be considered as an intermediate-purity Factor VIII concentrate. Following addition of 2% sucrose before freeze drying, Factor VIII, total protein and fibrinogen remain virtually stable (less than 15% loss) during heating of the material to 60, 64 or 68 degrees C for 24 to 72 h without changes of protein spectrum following heating. The heated product when stored at 4 degrees C remains stable for at least 3 months. In two severe haemophiliacs receiving this heat treated product, in vivo Factor VIII recovery was 100% with a mean half life of 10.2 h.

Acquired Immunodeficiency Syndrome

Quantitation of IgM, IgA and IgG rheumatoid factors by ELISA in rheumatoid arthritis and other rheumatic disorders.

We describe the evaluation of an enzyme-linked immunosorbent-assay (ELISA) for the measurement of IgM, IgA and IgG rheumatoid factor (RF). Results were obtained from sera of normal controls and patients with different rheumatic disorders in a cross-sectional study. Both human and rabbit IgG could be used as antigen in the assays. IgA-RF and IgG-RF were measured after pepsin digestion. The WHO reference preparation was used to standardise IgM-RF, but could not be used in the IgA- and IgG-RF assay, because neither IgA- nor IgG-RF could be detected in this standard serum. The ELISA for detection of RF is a highly sensitive and reproducible method and quantitation of results can be standardised. It yields good discriminative values for RA versus controls, in particular when more RF-isotypes are determined. In RA patients a correlation between IgM-, IgA- and IgG-RF concentrations does exist, although a wide variation was found in the ratio of these concentrations.

Adult

Orchidectomy alone in stage I nonseminomatous testicular germ cell tumors.

Fifty-four patients with Stage I nonseminomatous testicular germ cell tumors (NSTGCT) were treated from 1982 to 1984. In 1982 and 1983, the orchidectomy was followed by an exploratory laparotomy to conclude the dissemination study. In 1984, laparotomy was performed only if indicated. The mean follow-up was 29 months. A relapse occurred in 11 patients (20%). The relapse rate in patients who underwent exploratory laparotomy was as high as that in patients who did not. All patients treated for relapse by chemotherapy and surgery entered a complete remission for at least 1 year. It proved impossible to establish criteria for prediction of a subsequent relapse. Both serum tumor marker assays and roentgenography are important aids in diagnosing a relapse. With careful follow-up of Stage I NSTGCT patients, a wait-and-see attitude can be adopted until a relapse occurs.

Humans