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Biomedical subjects

R Pillai

Publications and source records attributed to R Pillai.

At least 19 recordsLinked to original sources

Role of immune response in the prognosis of carcinoma of the uterine cervix: can in vitro analysis provide a better framework for more effective management?

Cancer of the uterine cervix is the single largest female malignancy in India and also remains a major problem facing oncologists in other parts of the world. While advances in radiation therapy and surgical techniques have made the treatment of cervical carcinoma impressive, limitations to successful management still remain. In fact, the 5-year survival rate, stage for stage, has not improved in the United States or world wide in the past 40 years. With an estimated half a million women developing this disease annually, this lack of improved survival poses an international unresolved health problem. Immune response has been shown to be a major factor involved in the course of the disease for this cancer. Immunologic monitoring was also shown to be of effective value in assessing the prognosis for cervical carcinoma. We studied the various immunologic abnormalities in cervical cancer, the effects of radiation therapy on immune function, prospects of an immunologic staging system, the relationship between human papillomavirus infection and the immune response, and the possibility of using in vitro immunologic assessment to provide a better framework for more effective management of cancer of the uterine cervix.

Antibody Formation

Pathogenesis of oral submucous fibrosis. Relationship to risk factors associated with oral cancer.

Oral submucous fibrosis (OSF) is a chronic disease of the oral mucosa characterized by inflammation and a progressive fibrosis of the lamina propria and deeper connective tissues. It is a condition predominantly seen among people of Indian origin, and an epidemiologic survey done a decade ago showed no less than 250,000 cases in India, a figure that must have increased sharply. OSF is a condition with a high risk of malignant transformation; to date, no conclusive etiologic agent has been identified, although plenty of data have been generated on various aspects of the disease. These include genetic, carcinogenic, immunologic, viral, nutritional, and autoimmune possibilities, all of which also have been implicated in the development of oral cancer. This article reviews existing evidence on the pathogenesis of OSF and its relation to oral cancer and suggests a possible multifactorial model to explain the disease process.

Humans

Biological monitoring of cancer chemoprevention.

A major limiting factor in the successful implementation of cancer chemoprevention trials has been the determination of endpoints to measure efficacy and success. The use of the ultimate goal of such trials, namely, cancer incidence, as an endpoint has serious feasibility problems, including the need for large numbers of participants, long follow-up periods, and high costs. The application of biological markers as intermediate endpoints to reveal responses to chemopreventive agents within a short time and to act as surrogates for cancer is an attractive concept worthy of intense investigation. This study reviews some potential biological markers, including genetic, cellular, biochemical, and immunological, as well as their possible application to cancer chemoprevention.

Antineoplastic Agents

Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation.

The systemic inflammatory response to cardiopulmonary bypass was assessed in 20 patients who underwent elective coronary artery bypass grafting with flat-sheet membrane oxygenation (group I; n = 10; age, 59 +/- 5 years) or bubble oxygenation (group II; n = 10; age, 62 +/- 8 years). The duration of cardiopulmonary bypass was 46 +/- 12 minutes in group I and 47 +/- 15 minutes in group II. Plasma interleukin-6, plasma interleukin-1 beta, transpulmonary leukocyte counts, pulmonary hemodynamic variables, and respiratory index were determined in all patients perioperatively. The plasma interleukin-6 response (median [range]) was similar in both groups at the end of the operation, peaked 4 hours postoperatively (99 [30 to 320] pg/mL in group I; 123 [21 to 300] pg/mL in group II; p greater than 0.05), and remained elevated 48 hours postoperatively (76 [9 to 140] pg/mL in group I; 65 [25 to 159] pg/mL in group II; p greater than 0.05). No significant interleukin-1 beta response was demonstrated. Pulmonary neutrophil and lymphocyte sequestration was observed on commencement of cardiopulmonary bypass in group II but did not occur in either group on discontinuation of cardiopulmonary bypass. Pulmonary vascular resistance at the end of the operation (82 [48 to 320] dynes.s.cm-5 in group I; 119 [54 to 385] dynes.s.cm-5 in group II; p greater than 0.05) was similar to preoperative values (151 [30 to 327] dynes.s.cm-5 in group I; 185 [62 to 291] dynes.s.cm-5 in group II; p greater than 0.05). The respiratory index at the end of the operation was similarly and significantly increased in both groups (1.26 [0.92 to 4.17] in group I; 1.44 [0.73 to 3.30] in group II).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Oncogenesis of squamous carcinoma of the uterine cervix.

Carcinoma of the uterine cervix is the most frequent neoplasm among women in India, accounting for up to 85% of all female gynecological malignancies. In the United States, it accounts for about 48% of all female tumors and 4% of all cancer deaths of females. Epidemiological evidence suggests involvement of numerous risk factors in the etiology of cervical cancer, including sexual behavior, number of pregnancies, cigarette smoking, and venereal disease. Recent studies, however, tend to emphasize viral involvement in the development of cervical cancer along with concomitant cytogenetic and immunological changes. This review focuses on the roles of human papillomavirus infection, chromosomal abnormalities, and immune function changes in the pathogenesis of cervical carcinoma.

Carcinoma, Squamous Cell

Cardiac surgery: moving away from intensive care.

OBJECTIVE: To evaluate outcome in patients managed outside an intensive care unit after open heart surgery. BACKGROUND: The high cost of cardiac surgery is mainly due to the needs of traditional postoperative care. The requirements for intensive care and treatment has decreased with improvements in techniques of cardiac surgery and anaesthesia. In this setting the need to continue to depend on intensive care units for the recovery of cardiac surgical patients is questionable on clinical and economic grounds. DESIGN: Postoperative outcome in 245 patients over a four month period was studied prospectively. PATIENTS: Mean age of the patients was 63.2 years. They underwent a wide variety of operative procedures. Ninety percent of them recovered in a dedicated three bed cardiac surgical recovery area where the management protocol led to rapid extubation and step down in dependency care. RESULTS: Median time for ventilatory support was 90 minutes after transfer to the area. Only five patients were subsequently admitted to the general intensive care unit for prolonged respiratory and cardiac support. Ten patients were electively admitted to the general intensive care unit. Two deaths occurred in hospital in this group (0.8%). Four patients were ventilated for 24 hours in the recovery area itself and made an uncomplicated recovery. CONCLUSION: This study confirms that over 90% of patients undergoing cardiac surgery would recover safely and be treated effectively in a more economical area than intensive care.

Adult

Aortic root replacement: modifications of technique with improvements in technology.

Potential morbidity remains substantial in aortic root replacement. The tissues are often fragile, contributing to the risk of haemorrhage and postoperative complications. In the past surgery has been directed towards minimising haemorrhage by wraparound techniques and the right atrial fistula method of Cabrol. However, recent use of aortic homografts, collagen-impregnated grafts and tissue glues have reduced bleeding and simplified operative technique. Profound hypothermia and total circulatory arrest allows aneurysm resection to extend into the aortic arch. Between 1986 and 1991 25 aortic root replacements were carried out at the Oxford Heart Centre in 21- to 76-year-olds, 13 for aorto-annular ectasia (4 due to Marfan's syndrome), 7 for aortic dissection (2 Marfan's syndrome) and 2 for complications of previous aortic valve replacement. Three patients had homograft root replacement for aortic root endocarditis. We implanted 14 Medtronic composite grafts, 1 St Jude conduit and 7 collagen-coated Dacron grafts (Hemashield, Meadox) into which a Starr-Edwards valve was sewn, as well as 3 homografts. One patient with a massive chronic dissection following previous aortic valve replacement required an interposition graft to the coronary ostia. In the others, the coronary ostia were mobilised from the native aorta and directly implanted into the conduit. In dissections a ring of pericardium or GoreTex was used to buttress the coronary anastomoses. Six patients also required coronary artery grafting. Native aorta was excised and not wrapped around the conduit. Coagulation defects were corrected aggressively with platelets, fresh frozen plasma and cryoprecipitate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Combined cardiac and abdominal aortic aneurysm operations. The dual operation on cardiopulmonary bypass.

Eight patients underwent both cardiac operation and repair of abdominal aortic aneurysm. All had respiratory impairment and significant impairment of left ventricular function, whereas six patients had severe diffuse distal coronary disease. In all patients the cardiac procedure was performed first, and the patients continued to receive cardiopulmonary bypass. Rewarming was not commenced until the abdominal repair was well under way, to protect the vital organs. There were no problems in weaning the patients from bypass, and six of the patients were extubated within 24 hours; one required ventilation for 36 hours. One patient died of colonic infarction complicated by kidney failure without being extubated. Another patient who was initially extubated in 11 hours required reintubation because of poor lung function and eventually died of multisystem organ failure caused by bilateral lower limb ischemia that persisted despite embolectomies. All survivors are well and in New York Heart Association functional class I or II between 3 and 18 months postoperatively. We conclude that for patients considered unfit for abdominal aortic aneurysm operations because of the nature of the cardiac disease, the combined operation with cardiopulmonary bypass is both safe and effective.

Aged

Oncogenes and oncoproteins as tumor markers.

A major problem in the management of patients with cancer is the lack of specific tumor markers for the early detection, the accurate prediction of biological behavior and for accurate assessment of prognosis. A new and exciting answer to this problem may now become available following the discovery of specific genes associated with malignancy. The role of such genes and their products are now being identified and their role in cancer is under intense investigation. On a clinical level, these genes and their products may allow us to improve our understanding of disease etiology and provide more precise diagnostic, prognostic and therapeutic characterization of individual tumors. This paper discusses the possibilities of using the altered expression of oncogenes and tumor suppressor genes and their products in neoplastic tissues as markers for the diagnosis and prognosis of malignant disease. These data support the view that detailed analysis of such gene expression has the potential to predict a tumor's behavior as well as the response to different treatment modalities.

Biomarkers, Tumor

Thrombolysis and postinfarction ventricular septal rupture.

We studied all patients with postinfarction ventricular septal rupture referred to the Oxford Heart Centre for operation over a 4 1/2-year period. Twenty one women and 8 men were admitted to the Centre, 13 of whom had received streptokinase and 16 of whom had not. The median interval between symptomatic onset of myocardial infarction and the development of septal rupture was 24 hours for those treated by early thrombolysis (all streptokinase) and six days for those who were not. Of the 26 patients who underwent surgical repair, three were operated on less than 36 hours after streptokinase infusion, in one case within 12 hours of thrombolytic treatment. Macroscopic observation of the disintegrating myocardium showed muscle bundles dissected by blood rendered incoagulable by thrombolytic treatment, together with the histologic features of reperfusion injury. The overall surgical mortality rate for the streptokinase group was 33% and for the others 21%. The patient operated on within 12 hours of thrombolytic treatment recovered uneventfully. Six of seven surgical deaths were caused by left ventricular or biventricular failure and one by gastrointestinal hemorrhage. All survivors were in New York Heart Association classes II or III between 2 weeks and 4 1/2 years after operation. We conclude that thrombolysis leads to early breakdown of the interventricular septum after acute myocardial infarction but does not preclude early repair.

Aged

Lymphocyte subset distribution after radiation therapy for cancer of the uterine cervix. Possible prognostic implications and correlation with disease course.

An analysis of lymphocyte subpopulations was done in patients with cancer of the uterine cervix before and at different intervals after the commencement of radiation therapy. A common feature was a duration of T-cell and B-cell lymphopenia after therapy. The findings relating to the T-cell subsets were interesting. Although the CD4/CD8 ratio remained unchanged in Stages I/IIA for 24 months after treatment, patients with Stages IIB and III showed a lowering of the ratio immediately after treatment. Distinctive patterns of lymphocyte subset distribution were seen in a comparison between patients who were disease-free and those with recurrent disease. The CD4+ cell counts and CD4/CD8 ratio differed between the two groups, with consistent lowered values during the follow-up associated with recurrent disease. This study demonstrates the effects of radiation therapy in altering lymphocyte subset distribution, resulting in characteristic patterns which could be used as clinical and prognostic indicators.

Antibodies, Monoclonal

Oncogene expression and oral cancer.

Cancer of the oral cavity remains a major problem in the United States as well as in many other countries, some of which record as much as 30% of all their cancers to be in the oral region. Despite numerous advances in the fields of epidemiology and etiology, little is known of the molecular basis of oral cancer. Advances in the field of oncogenes have produced a tool to study the different stages of carcinogenesis, including transition from premalignant to malignant stages. These strategies have direct relevance to oral cancer where the premalignant stage is well defined. Preliminary studies into the expression and function of oncogenes suggest abnormalities including individual and multiple amplification of three or more types of these genes. This review briefly describes the concept of oncogenes, and their possible role in the development of neoplasia and specifically on studies in oral cancer.

Animals

AIDS, drugs of abuse and the immune system: a complex immunotoxicological network.

Two of the most interesting questions often asked about AIDS is why many people do not become immunodeficient or get complicating disease when first infected with Human Immunodeficiency Virus (HIV) and what are the "risk factors" making some individuals more susceptible to the disease. A large majority of people with AIDS have a well established history of drug and alcohol abuse. Both drugs of abuse and alcohol have immunotoxic properties as evidenced by a number of studies. These include marked changes in the cellular, humoral and other components of the immune defense mechanism. Such a compromise of the immune system can render it susceptible to the development of AIDS after HIV infection. This paper reviews the evidence suggesting possible links between substance abuse and its immunotoxicology, and their possible roles in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome

Immunological abnormalities in oral precancers.

Cancer of the oral cavity constitutes approximately 30% of all malignancies in India today. Many oral cancers first present as a precancerous lesion and hence it is important to understand the biological factors associated with such lesions. The immune system and its functioning is a significant element in the development of cancer. Considerable evidence exists suggesting that the immune response plays a role in regulating the development and growth of oral precancers. This paper reviews the various immunological abnormalities associated with oral precancers including cell surface changes, alterations in cell mediated immune reactions and humoral immune abnormalities.

Antibody Formation

Oncogene expression and prognosis in cervical cancer.

Cancer of the uterine cervix accounts for 80-85% of all female genital tract malignancies in India and also remains a major problem for oncologists in other parts of the world. A major concern regarding the disease is the lack of specific tumor markers for early detection, for accurate prediction of biological behaviour and for accurate assessment of prognosis. A new and exciting answer to this issue may now be available with the description of specific oncogenes and oncoproteins associated with this malignancy. On a clinical level these genes and their products may allow us to improve our understanding of disease etiology, and provide more precise diagnostic, prognostic and therapeutic characterization of individual tumors. This paper discusses the possibilities of using altered expression of oncogenes and their products in neoplastic tissue as markers for the diagnosis and prognosis of cervical cancer. These data support the view that detailed analysis of such gene expression has the potential to predict tumor behavior.

Female

Cocaine immunotoxicity: abnormal cytokine production in Hispanic drug users.

Peripheral blood lymphocytes from 47 Hispanic poly-drug users with a history of cocaine abuse were analyzed for in vitro production of interleukin-1 (IL-1), interleukin-2 (IL-2), gamma-interferon (IFN) and plasma levels of soluble IL-2 receptor (SIL-2R). Cocaine use was confirmed and quantified by analysis of hair and urine samples, and subjects were grouped into 3 based on the extent of cocaine metabolites detected. No significant differences in IL-1 and IFN production were seen between the 3 groups. However, subjects with higher levels of cocaine in hair also showed higher levels of IL-2. In addition, a positive correlation was seen between cocaine concentrations and IL-2 levels. A corresponding negative correlation was seen between cocaine levels and levels of plasma SIL-2R. These findings suggest modulation of the IL-2 network by cocaine in poly-drug users.

Adolescent