Modification of tumour blood flow using the hypertensive agent, angiotensin II

The effects of different doses of angiotensin II (0.02 to 0.5 microgram kg-1 min-1 on mean arterial blood pressure, tissue blood flow and tissue vascular resistance were investigated in BD9 rats. Blood flow was measured using the uptake of 125I- or 14C-labelled iodoantipyrine (125I-IAP and 14C-IAP). Spatial heterogeneity of blood flow within tumours, before and after angiotensin II infusion, was also measured using 14C-IAP and an autoradiographic procedure. Mean arterial blood pressure rose steeply with angiotensin II dose. Blood flow to skeletal muscle, skin overlying the tumour, contralateral skin, small intestine and kidney tended to decline in a dose-dependent manner. Blood flow to the tumour was also reduced (to 80% of control values) but there was no dose response. Blood flow to the heart was slightly increased and blood flow to the brain was unaffected by angiotensin II. Vascular resistance, in all tissues, was increased by angiotensin II infusion. The increase in tumour tissue was similar to that found in skeletal muscle and small intestine and is likely to be caused by a direct vasoconstricting effect of the drug rather than autoregulation of tumour blood flow in the face of an increase in perfusion pressure. The reduction in overall blood flow at the highest perfusion pressure was due to a preferential effect of angiotensin II at the tumour periphery. These results show that some tumours, at least, can respond directly to the effects of vasoactive agents

The response of tumour vasculature to angiotensin II revealed by its systemic and local administration to 'tissue-isolated' tumours.

A tissue-isolated preparation of the P22 rat carcinosarcoma was used to investigate the tumour vascular response to angiotensin II (ATII). In particular, the relative importance of systemic and local tumour factors was assessed by comparing tumour vascular resistance during systemic administration of ATII and during administration directly into the tumour-supplying artery. The effect of hypervolaemia on tumour vascular resistance was determined as well as the effect of ATII on oxygen metabolism. Tumour vascular resistance was increased by ATII in a dose-dependent manner. The response was biphasic with an initial peak in resistance followed by a lower plateau phase. Systemic administration of ATII was more effective in increasing tumour vascular resistance than direct administration. This suggests that systemic administration is not causing any reopening of previously collapsed tumour blood vessels. Further evidence for this is that hypervolaemia caused no reduction in tumour vascular resistance and that there was no difference in oxygen extraction by tumours between groups treated with systemically and directly administered ATII. A heterogeneous distribution of ATII receptors in the P22 tumour is a more likely explanation for the known heterogeneity of blood flow response to ATII

Characterisation of tumour blood flow using a 'tissue-isolated' preparation.

Tumour blood flow was characterised in a 'tissue-isolated' rat tumour model, in which the vascular supply is derived from a single artery and vein. Tumours were perfused in situ and blood flow was calculated from simultaneous measurement of (1) venous outflow from the tumour and (2) uptake into the tumour of radiolabelled iodo-antipyrine (IAP). Comparison of results from the two measurements enabled assessment of the amount of blood 'shunted' through the tumours with minimal exchange between blood and tissue. Kinetics of IAP uptake were also used to determine the apparent volume of distribution (VDapp) for the tracer and the equilibrium tissue-blood partition coefficient (lambda). lambda was also measured by in vitro techniques and checks were made for binding and metabolism of IAP using high-pressure liquid chromatography. VDapp and lambda were used to calculate the perfused fraction (alpha) of the tumours. Tumour blood flow, as measured by IAP (TBFIAP), was 94.8 +/- 4.4% of the blood flow as measured by venous outflow, indicating only a small amount of non-exchanging flow. This level of shunting is lower than some previous estimates in which the percentage tumour entrapment of microspheres was used. The unperfused fraction ranged from 0 to 20% of the tumour volume in the majority of tumours. This could be due to tumour necrosis and/or acutely ischaemic tumour regions. For practical purposes, measurement of the total venous outflow of tumours is a reasonable measure of exchangeable tumour blood flow in this system and allows for on-line measurements. Tracer methods can be used to obtain additional information on the distribution of blood flow within tumours

Resistance to flow through tissue-isolated transplanted rat tumours located in two different sites

The perfusion characteristics of the P22 carcinosarcoma were investigated in tissue-isolated tumour preparations in the ovarian and inguinal fat pads of BD9 rats. Tumours were perfused with a physiological buffer of known viscosity and changes in perfusion pressure were recorded at different perfusion rates in an ex vivo system. At perfusion pressures exceeding 30-40 mmHg tumour flow rate was directly proportional to the perfusion pressure in all tumours, indicating a constant resistance to flow. An apparent positive pressure difference across the tumour vasculature of 20-30 mmHg occurred under conditions of zero flow in either site. At low perfusion pressures, the flow resistance increased sharply due to increases in the geometric resistance of the tumours. These findings are in accord with previously published data. Geometric resistance increased with tumour volume in both sites and was approximately five times greater in the inguinal tumours than it was in the ovarian tumours, on a weight to weight basis. The dependence of tumour geometric resistance on perfusion pressure differs from the situation in normal tissues and may provide a means of manipulating the tumour microcirculation to the exclusion of the systemic blood supply. The dependence of geometric resistance on tumour site may partly explain why tumours located in different sites respond differently to various forms of therapy

Epidemiological profile and clinico-pathological features of pediatric gynecological cancers at Moi Teaching & Referral Hospital, Kenya

Background: The main pediatric (0–18 years) gynecologic cancers include stromal carcinomas (juvenile granulosa cell tumors and Sertoli-Leydig cell tumors), genital rhabdomyosarcomas and ovarian germ cell. Outcomes depend on time of diagnosis, stage, tumor type and treatment which can have long-term effects on the reproductive career of these patients. This study seeks to analyze the trends in clinical-pathologic presentation, treatment and outcomes in the cases seen at our facility. This is the first paper identifying these cancers published from sub-Saharan Africa. Method: Retrospective review of clinico-pathologic profiles and treatment outcomes of pediatric gynecologic oncology patients managed at MTRH between 2010 and 2020. Data was abstracted from gynecologic oncology database and medical charts. Results: Records of 40 patients were analyzed. Most, (92.5%, 37/40) of the patients were between 10 and 18 years. Ovarian germ cell tumors were the leading histological diagnosis in 72.5% (29/40) of the patients; with dysgerminomas being the commonest subtype seen in 12 of the 37 patients (32.4%). The patients received platinum-based chemotherapy in 70% of cases (28/40). There were 14 deaths among the 40 patients (35%) Conclusion: Surgery remains the main stay of treatment and fertility-sparing surgery with or without adjuvant platinum-based chemotherapy are the standard of care with excellent prognosis following early detection and treatment initiation. LMICs face several challenges in access to quality care and that affects survival of these patients. Due to its commonality, ovarian germ cell cancers warrant a high index of suspicion amongst primary care providers attending to adnexal masses in this age group

One-year clinical outcome of patients with nonvalvular atrial fibrillation: Insights from KERALA-AF registry.

BackgroundWe report patient characteristics, treatment pattern and one-year clinical outcome of nonvalvular atrial fibrillation (NVAF) from Kerala, India. This cohort forms part of Kerala Atrial Fibrillation (KERALA-AF) registry which is an ongoing large prospective study.MethodsKERALA-AF registry collected data of adults with previously or newly diagnosed atrial fibrillation (AF) during April 2016 to April 2017. A total of 3421 patients were recruited from 53 hospitals across Kerala state. We analysed one-year follow-up outcome of 2507 patients with NVAF.ResultsMean age at recruitment was 67.2 years (range 18-98) and 54.8% were males. Main co-morbidities were hypertension (61.2%), hyperlipidaemia (46.2%) and diabetes mellitus (37.2%). Major co-existing diseases were chronic kidney disease (42.1%), coronary artery disease (41.6%), and chronic heart failure (26.4%). Mean CHA2DS2-VASc score was 3.18 (SD ± 1.7) and HAS-BLED score, 1.84 (SD ± 1.3). At baseline, use of oral anticoagulants (OAC) was 38.6% and antiplatelets 32.7%. On one-month follow-up use of OAC increased to 65.8% and antiplatelets to 48.3%. One-year all-cause mortality was 16.48 and hospitalization 20.65 per 100 person years. The main causes of death were cardiovascular (75.0%), stroke (13.1%) and others (11.9%). The major causes of hospitalizations were acute coronary syndrome (35.0%), followed by arrhythmia (29.5%) and heart failure (8.4%).ConclusionsDespite high risk profile of patients in this registry, use of OAC was suboptimal, whereas antiplatelets were used in nearly half of patients. A relatively high rate of annual mortality and hospitalization was observed in patients with NVAF in Kerala AF Registry

Clinical characteristics and computed tomography findings in Arab patients diagnosed with pulmonary sarcoidosis

<b>Background and Objective</b> : Sarcoidosis is prevalent worldwide with significant heterogeneity across different ethnic groups. We aimed To describe the clinical characteristics and computed tomography findings among Arab patients with pulmonary sarcoidosis. <b> Methods</b> : A retrospective study of patient demographics, symptoms, co-morbid illness, sarcoidosis stage, treatment, pulmonary function and CT results. <b> Results</b> : Of 104 patients, most (77&#x0025;) were 40 years of age or older at diagnosis, and females in this category (&#899;40 years ) significantly outnumbered male patients (69/104 (66.3&#x0025;) vs. 35/104 (33.7&#x0025;), <i>P</i>=.003). The most common complaints were dyspnea (76&#x0025;), cough (72.1&#x0025;) and weight loss (32.7&#x0025;). The majority of patients displayed impairment in lung function parameters at presentation. However, significant impairment in forced vital capacity, percentage predicted (FVC&#x0025;) (&lt; 50&#x0025;) was present in only 17&#x0025; of patients. The most frequent CT finding was mediastinal lymph node enlargement in 49 patients (73.1&#x0025;). Parenchymal abnormalities indicating lung fibrosis were noted in 31 patients (46.3&#x0025;), and traction bronchiectasis was the most common (35.8&#x0025;) fibrotic pattern detected on CT scans. <b>Conclusion</b> : At presentation, clinical manifestations of sarcoidosis among this sample of Arab patients were similar to reports from other nations. Further studies are needed to explore the effects of race and ethnicity on disease severity in the Middle East