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Biomedical subjects

R Mohan

Publications and source records attributed to R Mohan.

At least 37 records · Page 2Linked to original sources

Compensation in three-dimensional non-coplanar treatment planning.

This paper presents a technique for producing uniform dose distributions within the target volume with non-coplanar field arrangements. The method is based upon the principle used for producing homogeneous dose distributions for a pair of fields in two dimensions, namely, that if the isodose distributions for the fields are made parallel to one another, the combined dose distribution will be uniform. For the three-dimensional non-coplanar case, homogeneous target dose distributions are obtained by designing field modifiers which produce a uniform dose distribution on the perpendicular bisector plane for each pair of fields. It is demonstrated that for three non-coplanar fields irradiating a spherical phantom with spherical target volumes, the target dose distribution will be homogeneous for any arbitrary non-coplanar field arrangement. Furthermore, this technique can be extended to any number of fields. Therefore, target dose distributions for non-coplanar plans can be as homogeneous as the coplanar case. An example of the application of the method to the treatment of rectal carcinoma with non-coplanar fields is given. Furthermore, it is demonstrated that the therapeutic ratio is improved over traditional methods for this clinical example.

Humans

The biological basis for conformal three-dimensional radiation therapy.

The recent introduction of new computer technology for treatment planning and computer-driven treatment delivery systems, such as multi-leaf collimators and on-line verification systems, has accelerated the development of 3-dimensional (3-D) radiation therapy as a modality for curative cancer treatment. The goal of 3-D treatment planning is to conform the spatial distribution of the high radiation dose to the shape of the tumor contour while concomitantly decreasing the volume of the surrounding normal tissues receiving high radiation doses. The improved precision of tumor coverage and the exclusion of normal tissues should permit tumor dose escalation and may enhance local tumor control. It has been suggested that any survival gains derived from improvements in local control may be offset by the subsequent appearance of distant metastases arising from micrometastases already present at the time of initial diagnosis. However, clinical and laboratory studies indicate that failure to control the primary tumor at the time of initial treatment significantly increases the incidence of metastatic dissemination. This phenomenon is consistent with the hypothesis that the enhanced mitotic activity associated with the re-growth process of locally recurring primary tumors promotes the multi-step transformation of non-metastatic tumor cells into clonogens with metastatic potential, leading to increased overall rates of metastatic disease. These biologic considerations provide support for the need to focus attention on the identification of more effective therapeutic strategies designed to eradicate the primary local tumor completely at the time of initial therapy and serve as the rationale for clinical studies using 3-D conformal radiation therapy.

Humans

Synthesis and biological activity of angiotensin II analogues containing a Val-His replacement, Val psi[CH(CONH2)NH]His.

The dipeptide mimic Val psi[CH(CONH2)NH]His (4) was incorporated into angiotensin II (AII) analogues to provide an octapeptide saralasin derivative (29) as well as tetrapeptide analogue 19. Three C-terminal tetrapeptides (21, 25, and 28) were also prepared. All compounds were tested for their ability to displace 3H-AII from rabbit adrenal gland homogenate and as antagonists of AII and AI on guinea pig ileum. The octapeptide analogue 29 was 700 times less active than the parent peptide 30. All the C-terminal fragments 19, 21, 25, and 28 have no measurable AII antagonist activity. Of the four tetrapeptide fragments, only 21 showed any appreciable binding activity.

1-Sarcosine-8-Isoleucine Angiotensin II

Recovery of rats from vitamin D-deficient mothers.

Two separate studies were conducted using weanling rats from either an unsupplemented, low vitamin D colony or a supplemented, adequate vitamin D colony. Severe hypocalcemia, slower increases in body weight gain, and lower apparent calcium, magnesium, and phosphorus balance values occurred in the rats from the low vitamin D colony fed a purified AIN-76A, vitamin D-devoid diet compared to rats from the vitamin D-adequate colony fed the same diet. Apparent calcium, magnesium, and phosphorus balance values, as well as most other measurements, in rats from the low vitamin D colony fed a purified AIN-76a, vitamin D-adequate diet were greater than or equal to those of rats never subjected to low vitamin D. This was suggestive of overcompensation in recovery from low maternal vitamin D. However, rats from the low vitamin D colony fed an unrefined (chow), vitamin D-adequate diet had lower apparent balance and bone values compared with rats from the vitamin D-supplemented colony fed the same diet. Presumably high levels of calcium, magnesium, and phosphorous in the unrefined diet prevented any overcompensation during recovery, as occurred with purified diets, from the earlier vitamin D deficiency. Overall, results indicated weanling rats from a low vitamin D colony had low vitamin D stores and were marginally vitamin D-deficient. In addition, recovery from the marginal deficiency had occurred to a large extent after feeding a purified, vitamin D-adequate diet. The results suggest the use of low vitamin D colony rats as a model for human, marginal vitamin D deficiency.

Animals

Interpretation of treadmill stress test in patients with coronary artery disease receiving beta blocker therapy.

Graded maximal treadmill exercise responses were studied before and after beta blockade (atenolol 100 mg once daily for 2 weeks) in 20 male patients with chronic stable angina. Beta-blocking effect consisted of significant reduction of resting heart rate (HR) by 21%, systolic blood pressure (SBP) by 12% and rate pressure product (RPP) by 30%. While the maximum exercise capacity was marginally increased by mean 1.7 min +/- 1.6 SD (P less than 0.001) under the influence of therapy, peak HR, SBP and maximum RPP were significantly lower (P less than 0.001) than in preatenolol exercise tests. Similarly, while the configuration and magnitude of ST segment depression did not differ materially between the pre and post atenolol tests, onset time of ST change was delayed and offset time shortened significantly. These parameters cannot be relied upon to assess the extent and severity of coronary artery disease (CAD) if stress test is carried out while the patient is on a beta-blocking drug. The overall sensitivity of the stress test to detect coronary disease is, however, not likely to be compromised because of negligible influence of beta-blockers upon ST segment depression provided maximally tolerated (not submaximal) exercise is performed. ST/HR slope, an exercise test variable known to correlate well with the extent of CAD, was shown to be uninfluenced by beta-blockade. Its measurement is therefore recommended in interpreting stress tests performed in patients receiving beta-blocker therapy. This, however, requires a meticulously prepared protocol of recording computer averaged QRST complexes and multilead ECG tracings at very frequent intervals throughout the exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Haemostatic abnormalities in brain tumours.

The coagulation profile of 25 patients with brain tumours was studied preoperatively, intraoperatively and postoperatively. Ten patients had abnormal coagulation status preoperatively. Surgical intervention led to either an alteration of preexisting abnormality or appearance of new coagulation abnormality. Disseminated intravascular coagulation and fibrinolysis occurred with equal frequency in patients with meningiomas and gliomas. The alterations as a result of surgery were transient and compensated rapidly.

Adult

Lack of biological activity of preproendothelin [110-130] in several endothelin assays.

A 21 amino acid peptide containing the prepropendothelin sequence from amino acids 110 to 130 and two intrachain disulfide bonds was synthesized and tested for biological activity in the following endothelin assays: 1.) a competition binding assay using [125I]ET-1 and dog heart membranes, 2.) three RIA's using 125I-ET-1, -2 and -3 and the respective anti-ET rabbit antisera; and 3.) a contractile activity bioassay using hamster aortic rings. The synthetic peptide which has been referred to as the "endothelin-like" peptide occurs 36 amino acids C-terminal to endothelin in the prepro-protein sequence. It contains only 40% sequence homology to the three endothelin isoforms, but has the same sequence and cyclization pattern of cysteines at positions 1, 3, 11 and 15. Despite the overall similarity in secondary structure to the three isoforms of endothelin and sarafotoxin S6b, preproendothelin [110-130] had no activity in any of the assays when tested at concentrations of 10(-10)M to 10(-5)M.

Amino Acid Sequence

Total body irradiation for bone marrow transplantation: the Memorial Sloan-Kettering Cancer Center experience.

In May 1979, Memorial Sloan-Kettering embarked on a programme of hyperfractionated TBI (HFTBI), 1320 cGy in 11 fractions over 4 days with partial lung shielding (1 HVL), followed by cyclophosphamide (60 mg/kg/d x 2d) for cytoreduction prior to allogeneic bone marrow transplantation (BMT). Anterior and posterior chest wall electron "boosts" were given to the areas blocked (600 cGy in 2 fractions) on the last two days of treatment. Since then, we have treated over 600 patients with HFTBI, the majority for allogeneic BMT. Several modifications have occurred over the years. We have added a "boost" electron dose of 400 cGy to the testes in all male leukemic patients; this reduced testicular relapses from a rate of 14% (4/28) to 0%. In an attempt to increase engraftment of T-depleted BMTs, we added one additional fraction; since our present dose/fraction was also increased to 125 cGy, we now deliver a total dose of 1500 cGy in 12 fractions over 4 days for allogeneic transplants. Tolerance to HFTBI has been excellent relative to the single dose (SD) regimen utilised prior to May, 1979. The incidence of fatal interstitial pneumonitis (IP) decreased from 50% in the SD regimen to 18% after the introduction of HFTBI. In children, the incidence of IP was only 4% with HFTBI. With the introduction of T-depleted marrows, fatal IP in adults has decreased also, e.g. to less than 10% in CML patients. With conventional BMT after HFTBI, relapse at 5 years has been exceedingly low (e.g. in children, 13% for ALL, 2nd remission and 0% for AML, 1st remission) and engraftment has been 100%. With matched T-depleted BMT, rejections have occurred in 15% overall; the incidence of graft failure has not been reduced by the higher dose of HFTBI. Relapses in this setting are equivalent to relapses with conventional BMT for AML, but appear to be increased for ALL. Radiobiological findings related to HFTBI will also be discussed.

Bone Marrow Transplantation

Myocardial protection by simple systemic hypothermia without aortic occlusion.

Systemic hypothermia at 25 degrees-28 degrees C without chemical cardioplegia was used in 908 patients undergoing coronary artery bypass grafting. Local coronary artery flow was interrupted only during grafting of a distal anastomosis. Systemic perfusion pressure was maintained at 80-100 mmHg, hematocrit at 20%-25%, and pCO2 and pH were monitored during hypothermia according to the alpha-stat principle, while the left ventricle was vented routinely. Proximal anastomoses were performed just before extracorporeal circulation was started by only partially occluding the ascending aorta. Preoperatively 61.9% of the patients had had a myocardial infarction, and 44% had unstable angina. In 14% a severe lesion of the main stem of the left coronary artery was present. Left ventricular function was moderately depressed in 25% and severely depressed in 8% of the patients. Forty-eight patients (5.3%) were aged 70 years or older. The mean number of grafts placed per patient was 3.3. Perioperative myocardial infarction occurred in 3%. Death due to left ventricular failure occurred in 0.4%. No left ventricular assist devices were needed; an intra-aortic balloon pump was used in 1%; positive inotropic support was required in 3.8% of the patients. These results indicate that systemic hypothermia alone provides safe myocardial protection and in certain cases may be the method of choice, particularly if aortic cross clamping or administration of cardioplegic solution is contraindicated. In addition, this method provides rapid revascularization of a severely ischemic zone, as present after unsuccessful PTCA procedures.

Aged

Nasopharyngeal carriage of Neisseria meningitidis in general population and meningococcal disease.

Nasopharyngeal carriage of Neisseria meningitidis was determined in the normal healthy population in Delhi at monthly intervals for a period of 2 years from January, 1986 to December, 1987. Of a total of 6513 individuals screened only 107 (1.64 per cent) were found to carry Neisseria meningitidis serogroup A. There was no age and sex difference in carriage. During the same period, data of laboratory confirmed cases of meningitis due to N. meningitidis serogroup A was obtained from 6 hospitals of Delhi which acted as sentinel centres. Of the total 11,870 pyogenic C.S.F. samples processed, only 557 (4.69 per cent) were due to N. meningitidis serogroup A. There was no correlation observed between the nasopharyngeal meningococcal carriage in the healthy population with the disease prevalence. There was no seasonal variation in nasopharyngeal carriage though upsurge in the number of meningococcal meningitis cases was noticed from January to April.

Adolescent

Comparative study of monocomponent insulins and conventional insulins on the course of diabetic nephropathy. A follow-up study.

Two matched groups of insulin requiring non-insulin dependent diabetic (NIDDM) patients with mild proteinuria (200 to 999 mg/day), one on mono component (MC) insulin therapy and the other on conventional insulins were studied for a 3 year period to evaluate the course of nephropathy in these two groups. Twenty-seven and 35 patients were followed-up in the MC insulin and conventional insulin groups respectively. In the MC insulin treated group, the percentage of patients showing deterioration in proteinuria was lower (11% vs 34%, P less than 0.05) and the percentage showing improvement was higher (48% vs 29%) compared to the conventional insulin treated group. Insulin antibody titres decreased significantly in the MC insulin group and serum C-peptide values decreased in both groups on follow-up.

Diabetes Mellitus, Type 2

Treatment planning for internal radionuclide therapy: three-dimensional dosimetry for nonuniformly distributed radionuclides.

A calculational approach is described that provides the spatially varying radiation absorbed dose, presented as isodose contours superimposed on CT images, from nonuniform and/or irregular cumulated activity distributions. CT images are read from magnetic tape and are displayed on a high-resolution color graphics display monitor. Source tissue geometries are defined on a series of contiguous CT images automatically (by an edge detection algorithm) or manually (using a trackball), thereby obtaining a three-dimensional representation of the various source volumes of activity. Dose calculations are performed using a radionuclide-specific absorbed dose point kernel in the form of a lookup table. The method described yields the spatially varying dose delivered to tumor and normal tissue volumes from a patient-specific cumulated activity distribution in a clinically implementable manner. This level of accuracy in determining normal tissue and tumor doses may prove valuable in the evaluation and implementation of radionuclides and radiolabeled compounds for therapeutic purposes.

Algorithms

Retinopathy in insulin dependent diabetes mellitus (IDDM) in south India.

The prevalence of diabetic retinopathy was assessed by direct and indirect ophthalmoscopy in a group of patients with insulin dependent diabetes mellitus (IDDM). Fourteen percent of patients had retinopathy. Proliferative retinopathy and severe background retinopathy including maculopathy were both seen in four percent of patients. It is possible that the lower prevalence rates for these complications is due to the shorter duration of diabetes in our patients.

Adult

Dose computations for three-dimensional radiation treatment planning.

The knowledge of radiation dose at all points of interest within a patient's body is essential for the evaluation of treatment plans and for the judicious selection of the best one from among a set of competing plans. This paper discusses the physical and geometric aspects of radiation dose distribution calculations necessary for three-dimensional treatment planning. A practical method of obtaining dose distributions for a given arrangement of beams and beam modifiers is with the aid of computer calculations based on mathematical formalisms derived from the principles of physics. The most accurate method of computing dose is by Monte Carlo stimulation of radiation transport. However, this method is extremely CPU time intensive and too complicated to implement for routine radiation treatment planning. Approximate semi-empirical methods have to be employed to compute dose distributions within reasonably short times. Conventional approximate methods do not yield results of adequate accuracy. Newer methods that are better able to take into account the three-dimensional nature of radiation transport have been introduced but require considerably greater computing capacity. Furthermore, computing power needs for dose calculations for three-dimensional treatment planning are one to two orders of magnitude greater than the corresponding needs of two-dimensional treatment planning. However, the concern for greater computing power requirements is being lessened somewhat with the advent of high speed computers and specialized hardware, and with the development of clever algorithms for speeding up dose calculations. For three-dimensional treatment planning some geometric issues, such as the calculation of dose at points in three-dimensional space, the incorporation of three-dimensional patient and beam geometry into a system for dose calculations, the choice of optimum grid spacing, radiological pathlength calculations, and algorithms for speeding up dose calculation, take on added importance compared to the corresponding issues for conventional two-dimensional planning. These issues are also discussed here briefly.

Algorithms

Autonomic function tests in cases of chronic severe anaemia.

Autonomic functions were studied in 30 adult cases of chronic severe anaemia (CSA) and equal number of age and sex matched healthy controls. Blood pressure and heart rate responses to standing, to respiration (expiratory-inspiratory ratio), to Valsalva manoeuvre (Valsalva ratio) and to hand immersion in ice cold water and given 1.8 mg of atropine intravenously were studied. Patients with CSA had significantly high basal pulse rate and low blood pressure as compared to control subjects (p less than 0.001). The expiratory inspiratory ratio was abnormal in 30% of the cases of CSA (p greater than 0.10) valsalva ratio was abnormal in 50% of cases (p less than 0.01) and postural tachycardia was observed in 60% of cases (p less than 0.001). Normal response to hand immersion in ice cold water was observed in 56.6% of cases (p less than 0.001). Atropine resulted in tachycardia in 73.4% of cases of CSA as compared to 86.7% of controls (p less than 0.10). All the cases of CSA showed one or more abnormal response and in 16.6% of cases all responses were abnormal.

Adult

Retinal revascularisation in diabetic retinopathy.

The case history of a 33-year-old diabetic patient who has had diabetes for 24 years is presented. When first seen in 1975 he had bilateral proliferative retinopathy with new vessels in the retinal periphery. He had large areas of capillary non-perfusion lateral to the macula in the right eye associated with the new vessels. Nine years later, after extensive repeated photocoagulation, revascularisation of large areas previously not perfused were seen. The vessels are in the plane of the retina and do not have the appearance of new vessels.

Adult

A method of correction for curvature and inhomogeneities in computer aided calculation of external beam radiation dose distributions.

This paper deals with the problem of finding the effective pathlength along a ray passing through a patient's outline and internal structure. The pathlength contributes to the correction applied for curvature and inhomogeneities in the computer-aided calculation of external beam radiation dose distributions. The pathlength is found by first determining the intersections of the ray with the contours defining the patient's body and the interior inhomogeneities. From these intersections the geometric length within each contour is obtained. This information is then employed in a treatment planning program for high energy gamma and X-rays and electrons, in which the radiation dose distribution is computed taking into account the actual inhomogeneous tissue structures. Other applications of the techniques described to problems in the field of radiation therapy are briefly discussed.

Computers