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Biomedical subjects

S P Kumar

Publications and source records attributed to S P Kumar.

At least 37 records · Page 2Linked to original sources

Effect of different levels of calorie restriction on azoxymethane-induced colon carcinogenesis in male F344 rats.

Epidemiological and animal model studies indicate that increased calorie intake increases the risk for colon cancer development. Previous studies in animal models restricted the calorie intake severely, and none of these studies have investigated a dose-response effect of different levels of calorie restriction on colon carcinogenesis. The present study was designed to investigate the effect of various levels of calorie restriction on colon carcinogenesis in male F344 rats fed the low and high fat diets and the effect of these diets on the activities of colonic mucosal and tumor ornithine decarboxylase (ODC) and protein tyrosine kinase. Starting at 5 weeks of age, groups of male F344 rats were fed the low fat or high fat diets ad libitum. At 7 weeks of age, all animals except the vehicle-treated groups were given s.c. injections of azoxymethane (AOM) (15 mg/kg body weight, once weekly for 2 weeks). Four days after the second injection, groups of animals were restricted to 90, 80, or 70% of total calories consumed by the high fat ad libitum group (i.e., 10, 20, and 30% calorie restriction, respectively). In the low fat groups, animals were restricted to 80% of total calories consumed by the low fat ad libitum group (i.e., 20% restriction). Thirty-six weeks after AOM injections, all animals were necropsied and colon tumors were used for histopathology and ODC and protein tyrosine kinase analysis. In the second experiment, the protocol was the same as above except that the animals were sacrificed 5 days after the second AOM injection and colonic mucosal ODC and protein tyrosine kinase activities were assayed. The incidence and multiplicity of colon tumors were significantly inhibited in animals fed the high fat 20% calorie-restricted and high fat 30% calorie-restricted diets, as compared to those fed the high fat ad libitum diet. The regression coefficient representing the dose-response effect of different levels of calorie restriction in both high fat groups is significant. Results also indicate that AOM treatment significantly increased the colonic mucosal ODC and protein tyrosine kinase activities. This stimulation was inhibited by feeding the calorie-restricted diets. ODC and protein tyrosine kinase activities were lower in the colon tumors of animals fed the calorie-restricted diets.

Animals↗

Pericardial effusion in primary hypothyroidism.

Pericardial effusion is reported to occur in 30% to 80% of subjects with hypothyroidism. However, these earlier studies were conducted when the diagnosis of hypothyroidism was only suspected and was confirmed only in the presence of classic clinical features. In contrast, the diagnosis has recently been established in the early mild stage or more often in an asymptomatic stage because of more frequent or routine determinations of thyroid function tests, especially in the elderly. Thus the subjects in the older studies were severely hypothyroid at the time of diagnosis and may not be representative of the present hypothyroid population. For this reason, 30 subjects with hypothyroidism were evaluated with echocardiography to reassess the evidence of pericardial effusion in this disorder. Only two subjects demonstrated pericardial effusion, and in only one of them with severe disease could the pericardial effusion be attributed to hypothyroidism, since it resolved on the patient's attaining the euthyroid state. Thus the incidence of pericardial effusion was only 3% to 6%, depending on the inclusion of one or both subjects, an extremely infrequent occurrence when compared with that of previous studies. Moreover, the occurrence of pericardial effusion in hypothyroidism appears to be dependent on the severity of the disease. Thus pericardial effusion may be a frequent manifestation in myxedema, an advanced severe stage, as previously found, but a rare association of hypothyroidism, an early mild stage, because of the timeliness with which the latter condition is nowadays detected.

Adult↗

Blood-brain barrier to hydrogen ion during acute metabolic acidosis in piglets.

The present study investigates the integrity of the blood-brain barrier to H+ or HCO3- during acute plasma acidosis in 35 newborn piglets anesthetized with pentobarbital sodium. Cerebrospinal fluid acid-base balance, cerebral blood flow (CBF), and cerebral oxygenation were measured after infusion of HCl (0.6 N, 0.191-0.388 ml/min) for a period of 1 h at a constant arterial PCO2 of 35-40 Torr. HCl infusion resulted in decreased arterial pH from 7.38 +/- 0.01 to 7.00 +/- 0.02 (P less than 0.01). CBF measured by the tracer microsphere technique was decreased by 12% from 69 +/- 6 to 61 +/- 4 ml.min-1.100 g-1 (P less than 0.05). Infusion of 0.6 N NaCl as a hypertonic control had no effect on CBF. Cerebral metabolic rate for O2 and O2 extraction was not significantly changed from control (3.83 +/- 0.20 ml.min-1.100 g-1 and 5.7 +/- 0.6 ml/100 ml, respectively) during acid infusion. Cerebral venous PO2 was increased from 41.6 +/- 2.1 to 53.8 +/- 4.0 Torr by HCl infusion (P less than 0.02) associated with a shift in O2-hemoglobin affinity of blood in vivo from 38 +/- 2 to 50 +/- 1 Torr. Cisternal cerebrospinal fluid pH decreased from 7.336 +/- 0.014 to 7.226 +/- 0.027 (P less than 0.005), but cerebrospinal fluid HCO3- concentration was not changed from control (25.4 +/- 1.0 meq/l). These data suggest that there is a functional blood-brain barrier in newborn piglets, that is relatively impermeable to HCO3- or H+ and maintains cerebral perivascular pH constant in the face of acute severe arterial acidosis. (ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Ventricular rhythm with intermediate rate in the neonate without heart disease.

Nonsustained, sustained, or incessant AVR, a form of VRIR, although infrequent, can present in the neonatal period. It must be considered in the differential diagnosis of wide QRS tachycardia. It seems to be different from VI, and it is asymptomatic and self-limited. It has good long-term prognosis and requires no treatment. These patients should not undergo invasive diagnostic evaluation unless symptoms develop.

Electrocardiography↗

Passage of the first stool in very low birth weight infants.

Times of first stool passage were studied in 171 infants who weighed less than 1,500 g at birth. Delayed passage (greater than 48 hours) was noted in 20.4% of this group. Significant differences were noted between the delayed and nondelayed groups for gestational age, presence of severe respiratory distress syndrome, and the time of the first enteral feeding. In very low birth weight infants, delay in the passage of the first stool is a common occurrence. This delay is probably due to physiologic immaturity of the motor mechanisms of the gut, lack of triggering effect of enteral feeds on gut hormones, and the presence of severe respiratory distress syndrome, which may singly or in concert adversely affect gastrointestinal motility.

Defecation↗

Effect of sympathetic nerve stimulation on cerebral blood flow in newborn piglets.

The purpose of this study was to determine the effect of sympathetic nerve stimulation on regional cerebral blood flow during the first 3 wk of postnatal development in piglets. Forty-one piglets ranging in age from 2 to 24 days were studied while anesthetized with 30% N2O, paralyzed and mechanically ventilated (PaCO2 = 35-40 mm Hg). Regional cerebral blood flow was measured with tracer microspheres (15 +/- micron) during electrical stimulation (15 Hz, 15 V, 3 ms) of the right cervical sympathetic trunk. Sympathetic stimulation decreased blood flow to the ipsilateral cerebrum (gray and white matter) (-15 +/- 2%), hippocampus (-9 +/- 2%), choroid plexus (-50 +/- 5%), and masseter muscle (-93 +/- 2%) compared to the contralateral side where blood flow to these regions was 74 +/- 4, 45 +/- 2, 258 +/- 26, and 24 +/- 4 ml/min/100 g, respectively (mean +/- SEM; p less than or equal to 0.05). The magnitude of the reduction in cerebral blood flow was not dependent on postnatal age as no significant differences were noted when the piglets were grouped according to age. Hypercapnia (PaCO2 = 64 +/- 5 mm Hg) increased blood flow 2- to 4-fold above control in all brain regions except the choroid plexus. The effect of sympathetic nerve stimulation was augmented during hypercapnia where blood flow to the ipsilateral cerebrum, hippocampus, and caudate nucleus was decreased by -34 +/- 4, -23 +/- 5, and -16 +/- 3%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Red cell glycolytic intermediates and adenosine triphosphate in preterm infants on the first day of life.

Red cell glycolytic intermediates and ATP were evaluated in 47 appropriate for gestational age preterm infants on the 1st day of life who were divided into three groups on the basis of gestational age: 28-30, 31-33, and 34-36 wk. The results were compared to those previously obtained in term infants. The concentrations of glucose-6-phosphate, total triose phosphates, and ATP were significantly higher than in term infants but appeared to be appropriately elevated for the young mean age of the red cell population. The concentration of red cell 2,3-diphosphoglycerate (2,3-DPG) was significantly decreased when compared to term infants and was lowest at 28-30 wk gestation. The content of red cell 3-phosphoglycerate was increased in term infants and was inappropriately elevated for the age of the red cell population at 28-30 wk gestation. This pattern of glycolytic intermediates was suggestive of a young red cell population metabolizing at an increased glycolytic rate with increased flow through the phosphoglycerate kinase step rather than the 2,3-DPG bypass in "normal" preterm infants. Two preterm infants of 28-30 wk gestation with low red cell intracellular pH were also evaluated and had markedly decreased concentrations of red cell 2,3-DPG and ATP and all phosphorylated intermediates distal to the phosphofructokinase reaction, indicative of a cross-over at the phosphofructokinase step secondary to acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3-Diphosphoglycerate↗

Chylothorax--a complication of chest tube placement in a neonate.

A premature infant with respiratory distress syndrome developed a left chylothorax after evacuation of a left tension pneumothorax. The Argyle catheter noted in the posterosuperior mediastinum possibly traumatized the thoracic duct. Although the infant's chylothorax resolved with conservative management, he subsequently died of severe bronchopulmonary dysplasia. The potential complication of chylothorax from thoracostomy tubes can be prevented by avoiding penetration into the posterosuperior mediastinum.

Chylothorax↗

Edema, hypoproteinemia, and zinc deficiency in low-birth-weight infants.

Three premature infants with zinc deficiency who had an unusual presentation with generalized edema and hypoproteinemia between 5 and 9 weeks of age are described. The infants were fed their own mother's milk, supplemented with a proprietary formula after the first 2 to 3 weeks of life. None of the infants had diarrhea, liver disease, or urinary protein loss. Treatment with oral zinc supplements led to rapid resolution of the edema, with an increase in values for serum proteins, alkaline phosphatase, and zinc. There was no recurrence of symptoms following discontinuation of zinc therapy 1 month later. At 1-year follow-up, all infants were doing well and had normal growth and development. As zinc plays a critical role in nucleic acid and protein synthesis, it is postulated that dietary zinc deficiency in the phase of rapid postnatal growth precipitated edema and hypoproteinemia in these infants. Zinc deficiency should be included in the list of causes of generalized edema in the low-birth-weight infant.

Diagnosis, Differential↗

Red cell metabolic alterations in postnatal life in term infants: glycolytic intermediates and adenosine triphosphate.

Red cell glycolytic intermediates and adenosinetriphosphate were evaluated in term infants from birth to on year of age and compared to values obtained from normal adults and subjects wit a population of a similar mean cell age. The concentration of glycolytic intermediates, with the exception of phosphoenolypyruvate were elevated at birth when compared to normal subjects, consistent with a young mean red cell population. The mean levels of red cell glucose-6-phosphate, fructose-6-phosphate, and "total triose phosphate" were elevated on days 1 and 4 of life when compared to both red cells from normal adults and subjects with a similar young mean red cell age. Glucose-6-phosphate steadily increased in concentration, peaked at 3 to 4 wk of age, and then progressively decreased in value. Total triose phosphate declined to a mildly elevated concentration by 3 to 4 wk of age. The mean concentrations of 2,3-diphosphoglycerate and adenosine triphosphate were normal on day 1, increased on day 4, and then declined by 3 to 4 wk to normal values, until 5 to 6 months when both increased. The mean phosphoenolpyruvate concentration was decreased on day 1 of age when compared to red cells of a similar mean age, but this decrease was not significant (P greater than 0.05). The mean concentrations of 3-phosphoglycerate increased at 3 to 4 wk of age and remained elevated for cell age at 11 to 12 months but this increase was no statistically significant (P greater than 0.05). 3-Phosphoglycerate levels did not change significantly throughout the first year of life. At one year of age, all red glycolytic intermediates and adenosine triphosphate were elevated when compared to red cells from normal adults, but were comparable to those observed in subjects with a red cell population of a similar mean cell age, consistent with the persistence of a young red cell population throughout the first year of life.

Adenosine Triphosphate↗

Red cell metabolic alterations in postnatal life in term infants: possible control mechanisms.

Red cell glycolytic intermediates and enzymes in term infants in the first year of life were correlated with the fetal hemoglobin concentration (%F), intra- and extracellular venous pH, plasma inorganic phosphorus (Pi) and pyruvate kinase (PK) activity. Changes in the non-age-dependent enzymes phosphoglycerate kinase, enolase, and phosphofructokinase correlated most significantly with the postnatal decline in %F (P less than 0.001), not the age of the red cell population, as reflected in PK activity. The age-dependent enzymes, hexokinase and glucose-6-phosphate dehydrogenase, however, correlated well with PK activity (P less than 0.001). The concentration of glucose-6-phosphate did not correlate significantly with the postnatal decline in %F (P greater than 0.05) or PK (P greater than 0.10), but correalted significantly with the plasma Pi concentration (P less than 0.001). "Total triose phosphate" and 2,3-diphosphoglycerate did not correlate with Pi. It appears from these studies that an extracellular factor, Pi alters the pattern of glycolytic intermediates in term infants and that the postnatal changes in phosphoglycerate kinase, enolase, and phosphofructokinase are unique to the "fetal" red cell and reflect passage from fetal to "adult" erythropoiesis.

Erythrocytes↗

Monocyte-induced potentiation of bovine fetal thymocyte mitogenic responses to concanavalin A.

Peripheral blood monocytes significantly potentiated the mitogenic response of bovine fetal thymocytes to Concanavalin A as measured by incorporation of [3H] thymidine into cellular DNA. Mononuclear cells obtained from either normal or Mycobacterium bovis sensitized cattle were cultured with or without purified protein derivative (PPD) for 24 hours at which time bovine fetal thymocytes and concanavalin A were added. After 3 days of culture, both activated or non-activated monocytes significantly potentiated Con A-induced blastogenic responses. of monocytes from thymocyte cultures completely abrogated thymocyte responses to Concanavalin A.

Animals↗

Red cell metabolic alterations in postnatal life in term infants: glycolytic enzymes and glucose-6-phosphate dehydrogenase.

The activities of red cell enzymes enolase (ENO), phosphoglycerate kinase (PGK), phosphofructokinase (PFK), glucose-6-phosphate dehydrogenase (G-6-PD), hexokinase (HK), aldolase (ALD), and pyruvate kinase (PK) were followed sequentially in term infants from birth to one year of age. At birth, red cell PGK and ENO activities were disproportionately elevated when compared to both red cells with a similar mean cell age and those with a younger mean cell age; red cell PFK was significantly decreased. There was a progressive full in PGK and ENO activities and rise in PFK levels toward normal values in the first year of life. The most significant changes in PGK, ENO, and PFK appeared to begin at 8 to 9 wk of age. ENO and PFK activities stabilized at approximately 5 to 6 months of age at values compatible with mean cell age; mean PGK levels remained mildly elevated at 11 to 12 months. The age-dependent enzymes G-6-PD, PK, ALD, and HK were all elevated in term newborns. G-6-PD and ALD progressively decreased in activity during the first year of life. PK and HK decreased in activity until 8 to 9 wk when there was a secondary rise in mean activity. Mean red cell G-6-PD, PK, ALD, and HK levels remained mildly to moderately elevated at 11 to 12 months of life, suggesting the persistence of a relatively young red cell population throughout the first year of life.

Adult↗

Follow-up studies of very low birth weight infants (1,250 grams or less) born and treated within a perinatal center.

The growth and development of inborn very low birth weight infants was evaluated in 50 of 60 survivors from 132 babies weighing less than or equal to 1,250 gm born July 1974 to December 1977. Mean +/- SE birth weight and gestation was 1,066 +/- 19.3 gm and 29.5 +/- 0.3 weeks, respectively, with 13 infants small-for-gestational age. Of the survivors, 26% weighed less than or equal to 1,000 gm. Male to female ratio was 1:1.4. Apgar scores less than or equal to 5 at five minutes occurred in 16% of the infants. Respiratory distress syndrome occurred in 56%, but only 10% (5/50) required mechanical ventilation. At 1 year, 46% small for gestational age (SGA) and 8% appropriate for gestational age (AGA) infants were less than the third percentile for weight. Major neurologic abnormality occurred in three infants (6%), one of whom is also blind. Grade V retrolental fibroplasia occurred in two others. Severe developmental delay (development quotient < 80, Gesell) occurred in these five infants and two other neurologically normal babies. Of 15 infants weighing less than or equal to 1,000 gm, two had major handicaps. Eight percent of the AGA infants and 30% of the SGA infants had major handicaps. These data indicate that infants born and treated in a perinatal center have a decreased incidence of asphyxia and severe respiratory distress syndrome and that the incidence of major handicaps is reduced, especially in the appropriate for gestational age baby.

Developmental Disabilities↗

Unusual artifacts in electrocardiographic monitoring.

Three unusual artifacts noted during Holter and telemetry monitoring, not previously described, are presented. Recognition of the artifacts prevented misinterpretation and wrong treatment. The clues to the identification of the artifacts and the need for avoiding wrong interpretation and inappropriate treatment are discussed. The cause of the telemetry artifact is discussed.

Adult↗