Cardiac rhabdomyomas and their association with tuberous sclerosis

A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas.     

Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer

Although micrometastatic cancer cells in lymph nodes can be detected by monoclonal antibodies against epithelial or tumor-associated antigens, it remains unclear whether these cells are precursors of overt metastases or shedded tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characteristics of such micrometastases. In lymph nodes classified as tumor free by conventional histopathological staging, tumor cells were identified with monoclonal antibody Ber-EP4 in 89 of 126 patients (71%) with completely resected (R0) esophageal carcinomas. Multivariate survival analysis underlined the strong and independent prognostic significance of Ber-EP4-positive cells in "node-negative" (pN0) patients. To assess the biology of Ber-EP4-positive cells, we established tumor cell lines from an immunohistochemically positive lymph node and the autologous primary tumor. p53 mutational analysis and multiplex-fluorescence in situ hybridization revealed common aberrations shared between both cell lines, whereas an insertion of chromosome 13 material in the short arm of chromosome 1 was only observed in micrometastatic cells. The tumorigenicity and metastatic potential of both cell lines were demonstrated in severe combined immunodeficient mice. In conclusion, our data provide first direct evidence for the malignant potential of micrometastatic cancer cells.     

Outcome of congenital lung abnormalities detected antenatally

To determine the outcome of congenital lung abnormalities, data were collected retrospectively between January 1991 and December 1996 on any foetus found to have a lung lesion on antenatal ultrasound. A total of 23 foetuses had lung lesions on antenatal ultrasound. In two foetuses the antenatal ultrasound showed bilateral enlarged "bright" echogenic lungs with evidence of hydrops. Both pregnancies were terminated and tracheal atresia was confirmed. In 15 foetuses the antenatal ultrasound appearance was of a unilateral "bright" echogenic lung. There was one case of bronchial atresia and two cases of congenital lobar emphysema, which all had surgery. In nine cases there was a reduction in the size of the lesion on serial antenatal ultrasounds and no lesion was detected after birth. In three cases a small lesion was present after birth on chest radiography. In six foetuses the antenatal ultrasound appearance was of unilateral cystic or mixed cystic and echogenic lung lesions. Two pregnancies were terminated; both had congenital cystic adenomatoid malformation. Four pregnancies were continued and three infants had surgery soon after birth and were confirmed to have had congenital cystic adenomatoid malformation. One infant has been managed conservatively. In conclusion, a definitive diagnosis cannot usually be made antenatally. A large lesion on initial scan does not necessarily predict a poor outcome. The natural history of small asymptomatic postnatal lesions is unknown and a long-term prospective study is needed to determine the outcome of these lesions.     

Regional myocardial dysfunction: evaluation of patients with prior myocardial infarction with fast CT

A prototype ultrafast cine computed tomographic (CT) scanner, designed specifically for cardiac imaging, was used to evaluate a preliminary series of patients with prior myocardial infarction (n = 21) and a control group without coronary artery disease (n = 5). Multilevel 50-msec CT scan exposures were obtained during peripheral intravenous bolus injections of contrast medium. A comparison was made between cine-CT scans and standard left ventriculographic images in assessing segmental left ventricular motion. Results indicate that cine CT, performed at sufficiently rapid speeds (20 scans per second) to allow useful analysis of regional ventricular wall motion, can provide adequate image quality. Analysis of 110 segments revealed a good correlation (90.9%) between the two techniques in characterizing normal from abnormal regional wall motion. Cine CT, based on this initial study, demonstrates considerable potential for evaluating not only cardiac chamber dimensions but also segmental wall dynamics.     

Kr-81m ventilation imaging: clinical utility in suspected pulmonary embolism

The results of Kr-81m/Tc-99m ventilation-perfusion (VP) lung scintigraphy were correlated with the results of pulmonary angiography for 74 patients suspected of having pulmonary embolism (PE). Among patients having a diagnostic scan, the sensitivity and specificity of scintigraphy were 91% and 94%, respectively. Also, 157 consecutive cases of Kr-81m/Tc-99m VP lung scintigraphy were reviewed, and the frequency of an indeterminate scan was found to be 22%. A similar frequency was found for VP scintigraphy with xenon-133. Of eight patients who had indeterminate scans due to the presence of a single VP mismatch, four were demonstrated to have PE by angiography. Kr-81m is an excellent agent for VP scanning in cases of suspected PE, offering accuracy in diagnosis as well as favorable physical properties.     

Should patients with a pre-operative prostatespecific antigen greater than 15ng/ml be offered radical prostatectomy?

Background Patients with prostate cancer with a pre-operative prostate-specific antigen (PSA) τ;15ng/ml who undergo radical retropubic prostatectomy (RRP) generally do not have a good outcome, yet may have organ-confined cancer and should be offered the option of surgery. Aim To assess the outcome of patients who underwent RRP with a pre-operative PSA ≥ 15ng/ml. Methods Thirty-four patients, mean pre-operative PSA: 25.46ng/ml (15.03–76.6) and mean Gleason score: 6.4 (5–9) were assessed. Results Two groups were identified. Group I: 41% (14/34) have no biochemical recurrence to mean follow up of 58 months (30–106). Mean PSA: 18.8ng/ml (15.03–25.84). Mean Gleason score: 6.1 (5–7). Clinical stage: T1c in 80%. No patient had seminal vesicle or lymph node involvement. Group II: 59% (20/34) have biochemical recurrence or died (3) from their disease to mean follow up of 66 months (36–98). Mean PSA: 28.9ng/ml (15.28–76.6). Mean Gleason score: 6.7 (5–9). Clinical stage: T1c in 25%. Eleven patients had seminal vesicle (8) involvement or positive lymph nodes (3) or both (2). Conclusion RRP seems feasible in patients whose pre-operative PSA is between 15 and 25ng/ml with stage T1c, Gleason score ≤ 7 and negative lymph node frozen section.     

Induction of chromosomal aberrations by dacarbazine in somatic and germinal cells of mice

Dacarbazine (DTIC) is a chemotherapeutic agent that has been successfully applied to treat various types of cancer such as Hodgkin's disease, malignant melanomas, soft tissue sarcomas and advanced neuroblastomas. Many of the patients are of reproductive age and express concern over the genetic risk of the treatment they receive. Therefore, DTIC was tested for its clastogenic effects in somatic and germinal cells of mice. In the bone marrow micronucleus assay DTIC induced micronuclei that increased linearly in the dose range 0-125 mg/kg. In a dominant lethal study DTIC gave a positive response at the dose of 500 mg/kg when conceptions occurred 5-16 days after treatment, corresponding to treated spermatids and early spermatozoa. The induction of heritable translocations was tested in that sensitive period. The observed translocation rate among the F(1) progeny of male mice treated with 500 mg/kg DTIC was 2.13% (P < 00.1 against the historical control of 0.05%). Assuming linearity of the dose-response effect, the point estimate was used to calculate a doubling dose for the induction of heritable translocations of 12 mg/kg. Alternatively, an induced translocation rate of 41.6x10(-6) per unit dose was calculated. Both figures indicate that an increased genetic risk may exist for male patients after chemotherapy with DTIC under the assumption that germ cells of mice and humans are equally sensitive to the clastogenic effects of DTIC. However, the genetic risk is restricted to conceptions within a period of 40 days after the end of chemotherapy, since the sensitive stages of spermatogenesis are spermatids and early spermatozoa.     

Pharmacologic therapy for diabetic retinopathy

Diabetic retinopathy remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop macular oedema (ME) or proliferative diabetic retinopathy (PDR). ME is manifest by retinal vascular leakage and thickening of the retina. The hallmark of PDR is neovascularisation (NV)--abnormal angiogenesis that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. Pharmacologic therapy aimed specifically at preventing vascular leakage and NV would be a welcome addition to the armamentarium. PDR and ME could be prevented by improved metabolic control or by pharmacologically blunting the biochemical consequences of hyperglycaemia (e.g., with aldose reductase inhibitors, inhibitors of non-enzymatic glycation or by protein kinase C [PKC] inhibition). The angiogenesis in PDR could be treated via growth factor (e.g., vascular endothelial growth factor [VEGF], insulin like growth factor-1 [IGF-1]) blockade, integrin (e.g., alpha-v beta-3) blockade, extracellular matrix alteration (e.g., with steroid compounds) or interference with intracellular signal transduction pathways (e.g., PKC and mitogen activated protein kinase [MAPK] pathway proteins). Some of these antiangiogenic agents may also prove useful for treating or preventing ME. Numerous potentially useful antiangiogenic compounds are in development; two drugs are presently in clinical trials for treatment of the preproliferative stage of PDR, while two are in clinical trials for treatment of ME.     

Letale Sinusvenenthrombose bei einer Patientin mit Mischkollagenose und sekund?rem Antiphospholipid-Antik?rper-Syndrom

Zusammenfassung Hintergrund: Assoziiert mit Kollagenosen findet sich gelegentlich ein Antiphospholipid-Antikörper-Syndrom, charakterisiert durch thromboembolische Gefäßverschlüsse im arteriellen oder venösen Gefäßsystem. Fallbeschreibung: Bei der Patientin manifestierte sich im Alter von 13 Jahren eine Mischkollagenose (Sharp-Syndrom) mit Arthritis und Myositis. Trotz immunsuppressiver Therapie traten wiederholt Schübe auf. Mit 15 Jahren entwickelte die Patientin eine Beinvenenthrombose als Ausdruck eines sekundären Antiphospholipid-Antikörper-Syndroms. Sie wurde auf eine orale Antikoagulation eingestellt, wandte sich im Alter von 16 Jahren jedoch der "Alternativmedizin" zu und beendete sowohl die Antikoagulation als auch die immunsuppressive Therapie. Etwa 4 Wochen später entwickelte die Patientin einen Status epilepticus, musste wegen respiratorischer Insuffizienz reanimiert werden und verstarb trotz intensivmedizinischer Therapie mit den Zeichen eines schweren Hirnödems und einer Einklemmung des Hirnstamms. Die Obduktion zeigte eine vollständige Thrombosierung der Sinusvenen als Ursache für das schwere Hirnödem. Schlussfolgerung: Eine Sinusvenenthrombose stellt eine seltene Manifestation eines Antiphospholipid-Antikörper-Syndroms dar. Im geschilderten Fall fiel die letale Thrombose zeitlich mit einer Phase von reaktiver Hyperkoagulabilität nach Beendingung einer Immunsuppressiva- oder Antikoagulationsbehandlung zusammen. Dieser tratische Fall unterstreicht, dass eine dauerhafte Antikoagulation bei Patienten mit Antiphospholipid-Antikörper-Syndrom unerlässlich ist. Abstract Background: The antiphospholipid (Huges) syndrome is a complication of connective tissue diseases characterized by thromboembolic occlusions of arterial and venous blood vessels. Case Report: At the age of 13, the patient developed connective tissue disease with arthritis and myositis. The course of her disease was characterized by frequent relapses despite immunosuppressive treatment. She developed deep venous thrombosis of her right leg as a manifestation of secondary antiphospholipid antibody syndrome at the age of 15 and was subsequently started on oral anticoagulation therapy. Approximately 10 months later, however, she decided to try alternative medicine and stopped both anticoagulation and immunosuppressive therapy. Only after 4 weeks she developed seizures followed by respiratory arrest with the need for cardiopulmonary resuscitation. Despite intensive care she died 2 days later with the signs of severe cerebral edema causing herniation of the brainstem. Autopsy confirmed the diagnosis of severe edema of the brain as a result of extensive thrombosis of all sinus veins. Conclusion: A complete sinus vein thrombosis is a rare manifestation of antiphospholipid antibody syndrome. The lethal thrombosis in this case occurred during a period of reactive hypercoagulability after termination of immunosuppressive and/or anticoagulation therapy. This case report underlines the need for long-term anticoagulation in patients with the antiphospholipid syndrome.