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Biomedical subjects

C Wittekind

Publications and source records attributed to C Wittekind.

At least 145 records · Page 8Linked to original sources

[The effect of acute cellular rejection on liver function following orthoptic liver transplantation. Quantitative functional studies with the 14C-aminopyrine breath test].

To test the effect of acute cellular rejection on liver function as represented by cytochrome-P-450 enzyme activity, the 14C-aminopyrine breath test (ABT) was performed prospectively in 46 patients (31 men, 15 women; mean age 48 [15-66] years) who had undergone a total of 50 orthotopic liver transplantations. Routine biochemical tests were performed daily until the 30th postoperative day, while the ABT was done daily on days 1-10 and three times weekly on days 11-30, and liver puncture biopsies were obtained once weekly or more often if there was clinical suspicion of rejection. Histologically confirmed cellular rejection occurred within the stated period of observation in eight patients (five women, three men; median age 45 [18-59] years). Results of routine laboratory tests (transaminases, bilirubin, thromboplastin time), as well as bile-flow and body temperature, did not vary uniformly. On the other hand, results of ABT at the time of rejection showed a decrease in all patients by an average of 65% (P < 0.01). Changes in the ABT preceded those in other tests by 1-2 days in four patients, being the only measurable functional abnormality in one. All rejection episodes responded to glucocorticoid pulse-treatment (three times 1 g methyl-prednisolone). Using ABT results as criterion, liver function became normal after the glucocorticoid injection within 4-11 days. These data indicate that the ABT is suitable in the routine monitoring of transplant function, thus facilitating early diagnosis and controlled treatment of acute cellular rejection.

Acute Disease↗

[Organ-preserving therapy in invasive bladder carcinoma].

With the aim of organ preservation, transurethral resection with subsequent radiotherapy (until 1985) or combined radio- and chemotherapy (since 1986) was undertaken as part of a prospective trial in 175 consecutive patients (137 men, 38 women; mean age 65 [31-90] years) with invasive bladder carcinoma, tumour stage T1-4 N0-3 M0. All patients had a transurethral resection, followed 2-6 weeks later by definitive radiotherapy at a dose of 50.4 Gy to the bladder in 28 fractions. 85 patients simultaneously with the radiotherapy received chemotherapy with cisplatin (25 mg/m2 daily) or carboplatin (65-75 mg/m2 daily) in the first and fifth weeks of radiotherapy. The 5-year survival rate for the whole group (including inoperable cases) was 50%. The survival rate as related to the T category was 53% for T1 (n = 26), 68% for T2 (n = 34), 45% for T3 (n = 94) and 22% for T4 (n = 17). 139 patients (79%) were left with a normally functioning bladder. Cystectomy was performed in 36 patients because of remaining tumour or recurrence after radiotherapy. Combined radio- and chemotherapy improved the histological remission rate, compared with an earlier control group with radiotherapy only, but it did not affect the survival rate. These data indicate that in advanced bladder carcinoma organ-preserving treatment with transurethral resection and definitive radiotherapy or combined radio- and chemotherapy can be successful.

Adult↗

[Rhabdomyolipoma of the right ventricle].

Echocardiography on a 29-year-old woman with exercise-unrelated tightness in the left chest for some months demonstrated an echo-dense space-occupying lesion in the outflow tract of the right ventricle (RV). Nuclear magnetic imaging revealed an ovular, fat-containing tumour, 3 x 2 x 2 cm in size. Because of threatened obstruction of the RV outflow tract removal of the tumour under cardiopulmonary bypass was undertaken. But complete removal was possible only by resecting a 2 x 3 cm area of the anterior wall of the RV, the resulting defect being covered with a Goretex patch. Histological examination identified the tumour as a rhabdomyolipoma. The patient was free of symptoms 1 year postoperatively.

Adult↗

Ductal adenocarcinoma of the pancreas. Histopathological features and prognosis.

Between 1972 and 1987, curative surgical resection (RO) was performed in 81 patients with ductal adenocarcinoma of the pancreas. In this study, slides from surgical specimens were reviewed, and histopathological features of the carcinomas were retrospectively reevaluated. Tumor stage was the most important prognostic factor: In UICC stages I, II, and III, the median survival times were 13, 16, and 8 mo, respectively. Lymph node involvement and direct extension of the tumor into adjacent peripancreatic tissue, as well as invasion into peripancreatic organs were found to significantly influence survival. Tumor infiltration of the lymphatic vessels was present in 74% of the resected carcinomas and significantly correlated with survival time. There was no relationship between survival and tumor size; furthermore, histological grade of differentiation, age, and sex had no influence on prognosis.

Adenocarcinoma↗

A 30-s PAS stain for frozen sections.

A modified periodate-Schiff's procedure technique for application in frozen section diagnosis is described. This simplified reaction performed using a microwave-oven procedure takes only 30 s and is useful in demonstrating mucin as well as mucin-containing cells. We found that this method facilitates frozen-section diagnosis.

Cryoultramicrotomy↗

Intragraft immune events after human liver transplantation. Correlation with clinical signs of acute rejection and influence of immunosuppression.

Evaluation of graft morphology is regarded as a cornerstone for diagnosis of acute liver graft rejection. Here we have studied the clinical relevance of biopsy findings obtained either by aspiration cytology or by histology in the first month after human liver transplantation, and have assessed the influence of immunosuppressive induction treatment on the incidence of morphological and clinical rejection. Results of 865 aspiration biopsies (TAC) and 155 core biopsies in 141 patients were correlated with the retrospective clinical diagnosis concerning the presence or absence of acute rejection. This analysis demonstrated that there are almost no false negative findings either in cytology or in histology (less than 0.1% of negative biopsies). In contrast, with both methods a large number of positive biopsy results were obtained that were without clinical correlate ("false positive" biopsies; 46% and 41% of positive cytologies and histologies, respectively). The rates of clinical and morphological acute rejections were differently influenced by the type of immunosuppressive induction protocol used. The incidence of clinical rejection was particularly low with a quadruple drug regimen when cyclosporine therapy was started immediately after transplantation (29% vs. 62% when introduction of cyclosporine was delayed for 2-5 days). Morphological rejections were similarly frequent with immediate and delayed introduction of cyclosporine at 2 mg/kg during quadruple therapy (65-75%) and were only reduced with initial high dose cyclosporine treatment (5 mg/kg) (35%). Antirejection treatment was not required in patients with morphological evidence of rejection but without clinical symptoms. The study demonstrates that cytology and histology are similarly reliable for exclusion and similarly unreliable for diagnosis of clinical acute rejection. The clinical relevance of positive biopsy findings is strongly influenced by the basic immunosuppressive treatment. Certain types of induction treatment can obviously alter the alloresponse in a way that no graft damage occurs despite the presence of marked intragraft immune activation. "False-positive" biopsy findings, therefore, seem to represent a qualitatively modified and self-limited type of intragraft alloresponse that is without clinical consequences ("incomplete" or "subclinical" rejection).

Biopsy, Needle↗

Results of hepatic resection and transplantation for fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is a tumor of the liver that can be differentiated from common hepatocellular carcinoma (HCC). Despite the exceptional role of the clinicopathologic signs and symptoms, true appraisal of the prognosis of the tumor is not clear and remains a controversial issue. To determine the long term prognosis of FLC more precisely, a retrospective study of 20 consecutive patients was performed, with analysis of selected pathologic factors, particularly the TNM staging system. Curative tumor removal (R0) was achieved by partial hepatic resection in 14 patients and total hepatectomy with subsequent replacement of the liver in six patients, respectively. The estimated overall five year survival rate was 36.6 percent. There was an advantage of partial versus total hepatectomy, with median survival times of 44.5 versus 28.5 months. Statistically significant better survival rates at five years were observed in patients with solitary tumors and in instances of absent regional lymph node metastases. Although other factors analyzed did not show significant differences, there was a tendency indicating individual tumor stage was the most significant determinant for prognosis. For further discussion of an apparently more favorable outcome of patients with FLC as compared with common HCC, detailed specification of the tumor stages seems mandatory. From the present analysis, the fibrolamellar variant could not be confirmed to be an independent indicator of better patient survival. The treatment of choice remains radical operation. The goal can, at best, be achieved by a therapeutic concept including partial as well as total hepatectomy, depending on the stage of the tumor.

Adolescent↗

DNA cytophotometric analysis of breast cancer. Follow-up for 10 years.

Forty-four cases of newly diagnosed invasive ductal breast cancer were studied by static cytometry at the time of diagnosis and were followed for 10 years to determine if the survival rate correlated with the nuclear DNA measurements. In 22 cases the stem line was in the 2c range, in 15 cases in the 3c range and in 7 cases in the 4c range. Thirty-four percent (n = 15) of the patients died of metastases during the first five years, 11% (n = 5) died of metastases between 5 and 10 years, and 55% (n = 24) survived for > 10 years without metastases. No correlation between increased tumor cell proliferation and recurrence of tumors could be found. In this study all patients with diploid tumors, tumor size T1 and negative lymph node status survived for > 10 years. In the presence of node metastasis (T1N1M0) all patients (n = 4) having tumors with the stem line in the 2c range survived for 5 years but only 2/4 for > 10 years. The percentage of patients surviving for 10 years showed no significant differences between the groups: in the 2c range, 59% (13/22); in the 3c range, 53% (8/15); and in the 4c range, 43% (3/7). The small number of cases does not allow definitive statistical conclusions, although the logistic regression analyses showed that stem line, pT and pN were the important prognostic factors for five-year survival. However, only pT and especially pN were of prognostic value for 10-year survival.

Breast Neoplasms↗

[Pathology of stomach cancer].

Dysplasias, the best-defined precancerous lesion of the stomach, are seldomly found alone, but most commonly in association with carcinoma. The established classification of gastric carcinomas includes the site, histological tumour type, grade of differentiation, R classification and pTNM classification with stage grouping. The Laurén classification is important in operative planning (extent of operation on the stomach and oesophagus). Additional conventional classification parameters are at present not proven independent prognostic factors.

Biopsy↗

Liver transplantation in HBs antigen (HBsAg) carriers. Prevention of hepatitis B virus (HBV) recurrence by passive immunization.

Liver transplantation in HBs-antigen (HBsAg) positive allograft recipients is associated with a high risk of HBV recurrence some time after surgery. So far, results of measures to prevent recurrent HBV-infection by means of treatment with interferon, hepatitis B vaccination and short-term passive immunization with hepatitis B immunoglobulin (HBIg) or monoclonal antibody to HBsAg (anti-HBs) have been disappointing. In the present study the results of long-term, anti-HBs monitored passive immunization with HBIg is reported. In 23 HBsAg-positive liver transplant recipients an anti-HBs level of greater than or equal to 100 IU/l was maintained for 6 or 12 months, respectively. The rate of recurrent infection was found to be less than 20% under HBIg substitution, whereas 11 graft recipients with no or only short-term HBIg prophylaxis were reinfected by month 15 after transplantation. HBV recurrence was associated with chronic liver disease and recurrent cirrhosis in the allograft.

Adolescent↗

Sonography and scintigraphy in the diagnosis of diseases of the major salivary glands.

This is a prospective study of 73 patients with diseases of the major salivary glands. The sonographic diagnosis could be confirmed by the course of the disease and/or the histologic result after operation in 67 (93%). In 29 patients, salivary gland scintigrams also were carried out. There was a tendency for signs of hypervascularization to be seen in patients with acute inflammation and reduction or loss of function in the presence of a chronic inflammation of the salivary glands. Scintigraphy did not provide diagnostic information on tumors of the salivary glands with regard to the type and location, with the exception of the Warthin's tumor. In selected cases it adds additional information, especially in functional therapy control.

Adenoma, Pleomorphic↗

Differentiation of liver graft dysfunction by transplant aspiration cytology.

Episodes of graft dysfunction are frequently observed after liver transplantation and can be due to different causes requiring specific therapy. In this study the usefulness and reliability of liver transplant aspiration cytology (TAC) for differential diagnosis of liver graft dysfunction is assessed. Out of more than 1500 TACs performed, 292 TACs, taken during episodes of liver dysfunction due to retrospectively defined causes, were analyzed. Immune activation and parenchymal damage in the aspirates were determined cytologically. In 63 episodes of acute rejection, marked immune activation was present in aspirate but not in blood, with varying degrees of hepatocyte damage and cholestasis. No or only minimal immune activation was observed in 86 cases of toxic, ischemic, or septic liver damage, but considerable parenchymal damage and cholestasis were observed. In 3 cases of hepatitis slight-to-moderate immune activation with large granular lymphocytes was found in the aspirate, while 17 cases of viral infection presented with slight-to-moderate immune activation in aspirate and blood. After successful treatment the cytologic patterns normalized, except when the cause of liver dysfunction persisted. Moreover, typical patterns of parenchymal changes were found for preservation damage of the liver (n = 108), fatty degeneration (n = 3), obstructive cholestasis (n = 5), and acute arterial ischemia (n = 2). One case of moderate subcapsular hematoma was the only complication observed (less than 0.1%). Thus, liver TAC is an easy, safe, and clinically useful method for differential diagnosis of liver graft dysfunction. In particular, differentiation between acute rejection and nonimmunologic causes of dysfunction is very reliable, but hepatitis and viral infections also present distinctive patterns in liver TAC.

Biopsy, Needle↗

Human versus animal insulin in the management of insulin-dependent diabetes: lack of effect on fetal growth.

It is generally accepted that the human placenta is impermeable to free insulin and that insulin present in the fetus is entirely of fetal origin. A recent study suggested that antibody-bound animal insulin crosses the placental barrier and may exert direct effects on fetal growth. We hypothesized that mothers with insulin-dependent diabetes treated with animal insulin would have infants with higher birth weights and ponderal indices compared with mothers treated with human insulin. We studied 209 mothers with insulin-dependent diabetes who were enrolled in our program and who delivered after 28 weeks' gestation: 170 were treated with animal insulin and 39 with human insulin. There were no differences between the groups in the mean birth weight (adjusted by gestational age at delivery) or ponderal index of the infants. The rate of macrosomia (birth weight greater than the 90th percentile for gestational age or ponderal index above 2.85) was similar in both groups. The sample size was adequate to yield a power of 80% to detect a difference between groups of 179 g or more in birth weight and 0.1 g/cm3 in ponderal index. We suggest that the type of insulin (animal versus human) used by the pregnant insulin-dependent diabetic mother has no bearing on fetal weight gain.

Adult↗

Mucoepidermoid tumor of the parotid gland showing a translocation (3;8)(p21;q12) and a deletion (5)(q22) as sole chromosome abnormalities.

The cytogenetic findings in a mucoepidermoid tumor of the parotid gland are described. In addition to a t(3;8)(p21;q12), all cells analyzed showed a deletion of part of the long arm of chromosome 5. Although the typical translocation of benign pleomorphic adenomas was found, histologic examination did not show remnants of a pleomorphic adenoma. Nevertheless, we assumed that the malignant tumor most likely arose in a preexisting pleomorphic adenoma. As a mechanism for malignant transformation, the loss of a suppressor gene located on the long arm of chromosome 5 is discussed.

Adenoma, Pleomorphic↗

[The Alagille syndrome in an adult].

Severe bleeding from gastric varices occurred in an 18-year-old male known, since he was three years old, to have liver cirrhosis with beginning protal hypertension. The cause of the portal hypertension was chronic cholestasis due to hypoplasia of the interlobular bile ducts. There was also peripheral pulmonary stenosis with pulmonary hypertension (106 mmHg systolic), and a posterior embryotoxon (arcus juvenilis). Skeletal anomalies, particularly of the vertebrae, and a striking facial dysmorphism provided the features of arteriohepatic dysplasia, Alagille's syndrome, an autosomal dominant disease generally becoming manifest during childhood. As the patient's liver functions were only slightly abnormal, liver transplantation was not indicated and a shunt operation performed. A septicaemia developed on the third postoperative day after an at first complication free course, and he died from right-heart failure.

Abnormalities, Multiple↗

Triploidy syndrome in a liveborn female.

We present the autopsy report of a liveborn triploid female, born after 36 weeks of gestation, who died at the age of 20 hours. External features were diagnostic: fetal hypoplasia, hypertelorism, microstomia, micro-and retrognathia, preauricular skin tag, low-set ears, and 3-4 syndactylia. All internal organs were hypoplastic. There were atrial and ventricular septal defects. Adrenals and kidneys were fused, the gallbladder was absent, and ovarian hilum cell were found to be hyperplastic. Triploidy, 69xxx, was confirmed cytogenetically. The placenta was hypoplastic and, microscopically, revealed a peculiar type of immaturity, so-called hydatidiform villous hypoplasia, findings which have not been previously reported. We suggest that the generalized fetal and placental hypoplasia and the severe hypoplasia of all internal organs are caused by a proliferative deficiency of the triploid cells. In addition, the nuclear DNA content was determined by cytophotometrically from placental stromal cells and was found to be about 50% above the normal diploid DNA value; i.e., a triploid DNA value was confirmed.

Abnormalities, Multiple↗