PubMed HealthSearch

Biomedical subjects

J M Gokel

Publications and source records attributed to J M Gokel.

At least 19 recordsLinked to original sources

Serial Doppler echocardiographic assessment of left and right ventricular filling for non-invasive diagnosis of mild acute cardiac allograft rejection.

Detection of acute cardiac allograft rejection (AR) remains an important clinical challenge. The role of Doppler echocardiography for the non-invasive diagnosis of AR is controversial, in particular with regard to milder forms of rejection. This study was designed to evaluate the potential of Doppler echocardiography for the non-invasive diagnosis of mild AR. Serial measurements of left and right ventricular filling parameters were performed in 31 heart transplant recipients and compared with simultaneously obtained endomyocardial biopsies. To account for biological and technical variability, consecutive rejection-free studies were used to calculate 95% confidence limits for mitral and tricuspid maximum early flow velocity and pressure half time. Measurements obtained during mild AR were then compared to these data. The study demonstrated that all parameters varied considerably between consecutive rejection-free examinations. Changes in left and right ventricular filling parameters during mild AR rarely exceeded the calculated 95% confidence limits. Thus Doppler echocardiography appears of little value for the non-invasive diagnosis of mild acute cardiac rejection.

Adult

[Lennert's lymphoma and glomerulonephritis].

A 49-year-old man noticed a swelling below the left ear. The histological diagnosis was chronic lymphadenitis with a small cell epithelioid cell reaction. A short time later he developed oedema of the legs, proteinuria and elevated serum creatinine levels (1.89 mg/dl). Renal biopsy showed mesangioproliferative glomerulonephritis. Over the next two years the tumour in the left side of the neck gradually increased in size. Computed tomography showed a space-occupying lesion 5 x 7 cm in the vicinity of the left parotid gland, with evidence of infiltrative growth. Histological examination of the tumour after removal revealed epithelioid cell tissue with numerous lymphocytes, and led to the diagnosis of a lymphoepithelial lymphoma (Lennert's lymphoma), a T-cell lymphoma of low malignancy. Complete remission was achieved after four chemotherapy cycles (COPP schedule) in reduced doses (creatinine concentration 2.09 mg/dl, creatinine clearance 36 ml/min); creatinine clearance subsequently improved to 63 ml/min. Later, however, the tumour recurred and the patient went into terminal renal failure, dying four years after the lymphoma first appeared. The glomerulonephritis may conceivably have been a paraneoplastic phenomenon.

Antineoplastic Combined Chemotherapy Protocols

Fatal infantile mitochondrial cardiomyopathy and myopathy with heterogeneous tissue expression of combined respiratory chain deficiencies.

A 5-month-old boy died of progressive heart failure that started at the age of 3 months. Autopsy revealed a mitochondrial cardiomyopathy and a mitochondrial myopathy of the limb muscle and diaphragm. Cytochemically random defects of cytochrome c oxidase were visualized by light and electron microscopy in the diaphragm and especially the heart muscle, the limb muscle showing a diffuse attenuation whereas the liver and kidneys reacted normally. The activities of NADH-dehydrogenase (complex I) and cytochrome c oxidase (complex IV) were severely diminished (20% residual activity of controls) in the skeletal and heart muscle. In the heart, succinate cytochrome c reductase (complex II/III) was additionally decreased to the same degree. Loss of cytochrome c oxidase activity was based on a reduction of both mitochondrial and nuclear derived subunits in the heart and diaphragm as revealed by immunohistochemical analysis, whereas the limb muscle showed a normal immunoreactive protein content. The results illustrate heterogeneous tissue expression of respiratory chain enzyme defects and demonstrate that a cardiomyopathy may be the leading presentation of a mitochondrial disorder in early infancy.

Cardiomyopathies

Contractility of the transplanted, denervated human heart.

The purpose of the study was to characterize the contractility of the transplanted human heart and to evaluate possible adverse effects of denervation or structural changes of the myocardium or coronary vessels. As an index of contractility, the linear slope k of the end-systolic pressure/dimension relationship during afterload increase with angiotensin II was determined by M-mode echocardiography in 34 heart transplant recipients and 20 healthy control subjects. Baseline findings for end-systolic diameter and systolic blood pressure were normal and similar in both groups, but the transplanted hearts performed at a significantly lower end-systolic wall stress (40.4 +/- 12 gm/cm2 vs 49.9 +/- 11 gm/cm2, p less than 0.001). Comparable increase of afterload was achieved in heart transplant recipients with significantly (p less than 0.001) less angiotensin II, which indicates increased vasoconstrictor sensitivity. Contractility index k did not differ between heart transplant recipients (12.95 +/- 4.9 mm/100 mm Hg) and control subjects (12.78 +/- 2.8 mm/100 mm Hg). This finding is consistent with a normal contractility of the transplanted, denervated human heart. Normal baseline contractility therefore is an intrinsic property of the intact heart, which is independent of autonomic neural control. Contractility was not compromised by increasing interval from transplantation or the presence of mild acute rejection or mild interstitial fibrosis. Mildly impaired contractility (k greater than 2 SD of k in control subjects) in four heart transplant recipients (12%) was neither associated with structural myocardial or coronary changes nor with rejection episodes or graft ischemic time. One may speculate that impaired contractility, which is present in a minority of heart transplant recipients, results from pretransplantation damage.

Adult

Expression of HLA-D subloci DR and DQ by breast carcinomas is correlated with distinct parameters of favourable prognois.

The expression of HLA-D region products HLA-DR, DQ and DP by primary breast carcinomas was examined for its relationship to standard prognostic parameters. A positive correlation was found between the expression of HLA-DR and the differentiation state of the tumour (P = 0.02) and the expression of progesterone receptors (P = 0.002), two parameters which are associated with good prognosis and with each other. No correlation was seen between these parameters and the expression of HLA-DQ or HLA-DP. In contrast, tumour diameter was inversely correlated with the expression of HLA-DQ (P = 0.0004) although no association was observed between this parameter and HLA-DR expression. Essentially all HLA-DQ positive tumours had a diameter of less than 2 cm although these represented only 50% of the tumours of this size examimed. These data show that in breast carcinomas HLA class II expression is correlated with several distinct parameters of good prognosis and suggest that HLA-DQ expression may define a subtype of T1 tumours.

Adult

[Detection of acute graft rejection with Fourier transformation of the surface ECG in long-term follow-up of heart transplantation].

Up to now, diagnosis of acute rejection after heart transplantation (HTx) has been based on endomyocardial biopsy (EMB), but there is the need for reliable noninvasive parameters. Spectral analysis of the surface ECG with fast Fourier transformation (FFT) has been shown to be useful for rejection monitoring in the immediate postoperative phase. We tested the method in the chronic phase after HTx: the QRS complex (2 bipolar leads, position tattooed with Indian ink) was repeatedly analyzed with FFT (segment size 120 ms, 512 points. Blackman-Harris window) in 38 patients for 4-36 months after HTx. In mean intervals of 3 months, 254 checkups with FFT and EMB were performed on the same day. EMB revealed 28 acute rejection episodes in 21 patients, and ongoing rejection was diagnosed in 17 EMB. During rejection the frequency content of the QRS complex between 70 and 110 Hz increased in 25/28 rejection episodes (89%) and in 15/17 ongoing rejection cases, whereas in the time domain no specific changes could be seen. The QRS-amplitudes did not reliably indicate rejection, but decreased slowly during follow-up. After therapy the spectral changes disappeared within weeks. No signs of acute rejection were evident in 209 EMB: in 156/209 frequency analyses (77%) the spectra were constant, in 45/209 cases the frequency content increased, and eight analyses could not be evaluated. As the number of rejection crises decreased in the first postoperative months, there was an increasing number of false positive FFT analyses (positive predictive value 35%). Thus, a change of frequency content requires control by biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy

The influence of rejection episodes on the development of coronary artery disease after heart transplantation.

Since 1981, 77 of 116 patients undergoing heart transplantation (HTx) have survived from 6 months to 8 years. Graft control involved a total of 871 endomyocardial biopsies (EMB) and 141 angiographies. Sixteen patients developed coronary artery disease (CAD) manifesting itself 7-60 months after HTx (20.7%). These patients (15 male, 1 female) experienced multiple rejection episodes (RE) and more than half suffered from hypercholesterolaemia and hypertension (n = 10). A mean rejection score (Billingham grading) of greater than 1 (mean = 1.6 +/- 1.1) was calculated in all patients with CAD at the time of angiography or autopsy. By contrast, the mean rejection score ranked less than 1 in patients with undetectable or resolved CAD (means = 0.4 +/- 0.38). This rate is not remarkably different from the rejection score in patients (n = 61) without CAD (mean = 0.2 +/- 0.4). The 8 patients alive (56 +/- 18 months) showed a low number of RE/year (mean = 1.1 +/- 0.4) compared with means = 1 +/- 0.9 in patients without CAD. Eight patients expired within a short period (mean = 31 +/- 26.9) and had a significantly higher number of RE/year (mean = 4.3 +/- 2.9; P less than 0.01 vs. no CAD, CAD alive). Autopsy (n = 6) and angiographic studies (n = 46) demonstrated diffuse, concentric, obliterative arterial disease in all vessels (type A) in 6 patients (RE/yr: mean = +/- 5.5 +/- 2.3), single stenoses in major coronary vessels (type B) in 7 patients and ordinary atherosclerosis (3-vessel disease) comparable to ischaemic heart disease (type C) in 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease

Significance of salvage lymphadenectomy in the therapeutical concept of advanced nonseminomatous germ cell tumors.

A retrospective study reports 65 patients with metastatic disease from nonseminomatous germ cell testicular tumors who underwent a salvage lymphadenectomy either to remove a residual mass or to confirm a complete clinical response after polychemotherapy. Scarring was found in 23 patients (35%), differentiated teratoma in 25 patients (39%) and residual cancer in 17 patients (26%). Of the 12 patients staged as complete responders 2 were found to have cancer, 4 teratoma and 6 fibrosis. Neither tumor markers nor CT scan could accurately predict which patients with residual masses would have cancer, mature teratoma or necrosis. Thus needle biopsy or limited resection is inadequate in its ability to detect persistent vital tumor. After a follow-up of 10-106 months 49 patients (75%) are living with no evidence of disease. 12 patients (19%) died of tumor progress. The most critical prognostic determinant was the nature of the tissue resected. 21 (91%) of 23 patients with only fibrous or necrotic elements are living with no evidence of disease. However, of 17 patients with persistent cancer in the resected tissue only 8 patients (47%) fared well. Our experience confirms the original concept which called for postchemotherapeutic tumor surgery in all patients who demonstrated either a partial or complete clinical response.

Adult

[The value of immunofluorescence on frozen sections and immunoperoxidase methods on paraffin sections with different types of glomerulonephritis comparative study].

171 kidney biopsies were tested with the peroxidase- antiperoxidase (PAP)-method on paraffin sections. A comparison of the PAP-results with corresponding ones for the immunofluorescence method (IMF) on frozen sections was possible in 131 of the biopsies. When results of the 2 techniques were compared, outcomes showed a very strong accordance for both methods in tissues of postinfectious and perimembraneous GN an a strong accordance in mesangioproliferative GN tissue. In membrano-proliferative GN the immunopathological findings were more readily delinated with the PAP-method than with IMF. Cases involving IgA-nephritis, focal sclerosis and lupus nephritis with smaller deposits did not show consistant reactivity in the PAP-method as compared with IMF. 40 kidney biopsies, not examined by IMF, were diagnosed as GN by light microscopy and could be shown in 29 cases to contain evidence of an immune pathogenesis with the PAP-method.

Biopsy

Cyclosporine-associated nephropathy in patients with heart and bone marrow transplants.

The morphology of kidneys from heart (n = 55) and bone marrow (n = 112) transplant recipients treated either with cyclosporine (CSA) or conventional immunosuppression was investigated at autopsy. The major findings were: In the bone marrow transplant recipients glomerular collapse, tubular atrophy, interstitial fibrosis, striped form, CSA-associated arteriolopathy and thrombi in glomeruli and/or arterioles were more often found in the CSA group as compared to conventional immunosuppression. In the heart transplant recipients glomerular collapse and obsolescence, tubular atrophy and intimal fibrosis in arteries were more frequent in the CSA group. Vascular interstitial toxicity known to be associated with CSA treatment from renal transplant patients was found in 54% (25% severe) of the bone marrow and 19.5% (9.7% severe) of the the heart transplant recipients. The prevalence of vascular interstitial toxicity in bone marrow versus heart transplant recipients is possibly due to higher CSA dosage and pretreatment with cytostatic drugs and irradiation. Analyses of the lesions from early stages to the full picture of vascular interstitial toxicity suggests that CSA causes a form of thrombotic microangiopathy with focal glomerular and/or arteriolar thrombosis followed by typical CSA-associated arteriolopathy which results in interstitial fibrosis with tubular atrophy.

Adult