Breast filariasis--an unusual presentation.
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Biomedical subjects
Publications and source records attributed to A Gupta.
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A case is described where monitoring regional cerebral oxygenation using a microprobe brain tissue electrode detected important changes in cerebral oxygenation not identified by jugular venous bulb oximetry. The possible benefits of monitoring regional cerebral oxygenation and the possible pitfalls of only monitoring global cerebral oxygenation are discussed.
Somatostatin receptor expression, which was not a previously described marker for Hürthle cell cancer of the thyroid, was demonstrated by in vivo imaging with (111)In-pentetreotide in three patients. This phenomenon not only adds another imaging technique to the nuclear medicine armamentarium for detecting recurrent and metastatic cancer in patients with Hürthle cell cancer but also opens up an alternative therapeutic avenue with somatostatin analogs or their radiolabeled compounds.
One thousand six hundred ninety-four (1694) cases of carcinoma cervix have been reviewed out of a total of 11919 malignancies, over a period of 4 years (1992-1995), in the department of radiotherapy, Safdarjung Hospital, New Delhi. The epidemiological features studied showed that there was a gradual decline in the total number of cases, age at presentation and parity. There has been a definite increase in the proportion of adenocarcinoma cases. Adenocarcinoma of cervix showed statistically significant preponderance in comparatively younger age group viz, 40-60 years (p < 0.005); 76% of overall cases were illiterate; 77% of cases belonged to rural/urban slum settings compared to 23% which were purely urban in origin. About 65% cases had haemoglobin levels below 10 g/dl at the time of presentation.
QUESTIONSome of my pregnant patients have trouble functioning because of morning sickness. In particular, they are afraid to take medications. They end up losing weight, quitting work, and dropping out of other activities. What can I do to allay their fears?ANSWERWomen often benefit from knowing that they are not alone in having this problem, that morning sickness typically does not harm a fetus, and that safe therapies are available. Psychological and medical support is very important. Other causes of nausea and vomiting must always be ruled out. The Motherisk Program has a clinic and hot-line line for patients with severe morning sickness.
METHODS: Thirty-two patients with clinical node-negative breast cancer underwent sentinel node localization study as part of a National Cancer Institute-sponsored multicenter trial. Anatomical and histopathologic characteristics of sentinel lymph node (SLN) and a kinetic analysis of nodal uptake were studied. Patients were injected with 1 mCi/4 ml unfiltered 99mTc-sulfur colloid in four divided doses around the palpable lesion or immediately adjacent to the excision cavity if prior biopsy was performed. SLN biopsy was performed 1.5-6 hr (mean = 3 hr) postinjection. Intraoperative localization was performed using a gamma probe. All patients underwent complete axillary dissection. RESULTS: SLN was identified in 30 of 32 (94%) patients. There were no false-negative SLN biopsies. CONCLUSION: This study supports the clinical validity of SLN biopsy in breast cancer and confirms that, unlike the blue dye technique, the learning curve with unfiltered 99mTc-sulfur colloid and the gamma detection probe is short, and SLN localization is achievable in over 90% of cases by surgeons with modest experience. The use of unfiltered 99mTc-sulfur colloid (larger particle size) with larger injected volume permits effective localization of SLNs.
Osteoclasts are the primary cells responsible for bone resorption. They are exposed to high ambient concentrations of inorganic phosphate (Pi) during the process of bone resorption and they possess specific Pi-transport system(s) capable of taking up Pi released by bone resorption. By immunochemical studies and PCR, we confirmed previous studies suggesting the presence of an Na-dependent Pi transporter related to the renal tubular "NaPi" proteins in the osteoclast. Using polyclonal antibodies to NaPi-2 (the rat variant), an approximately 95-kD protein was detected, localized in discrete vesicles in unpolarized osteoclasts cultured on glass coverslips. However, in polarized osteoclasts cultured on bone, immunofluorescence studies demonstrated the protein to be localized exclusively on the basolateral membrane, where it colocalizes with an Na-H exchanger but opposite to localization of the vacuolar H-ATPase. An inhibitor of phosphatidylinositol 3-kinase, wortmannin, and an inhibitor of actin cytoskeletal organization, cytochalasin D, blocked the bone-stimulated increase in Pi uptake. Phosphonoformic acid (PFA), an inhibitor of the renal NaPi-cotransporter, reduced NaPi uptake in the osteoclast. PFA also elicited a dose-dependent inhibition of bone resorption. PFA limited ATP production in osteoclasts attached to bone particles. Our results suggest that Pi transport in the osteoclast is a process critical to the resorption of bone through provision of necessary energy substrates.
T lymphocytes normally express their Ag receptors in association with the CD3 proteins, which include CD3zeta. In CD3zeta eta(null) mice thymic and peripheral T lymphocytes do not express the TCR/CD3 complex on their surface due to retention in the endoplasmic reticulum of the remaining polypeptide chains. However, intestinal intraepithelial lymphocytes (iIEL) of CD3zeta eta(null) mice do express surface TCR, because the Fc epsilonRI gamma chain replaced the CD3zeta chain in the TCR/CD3 complex. Here we report that in a subset of CD8alpha alpha+ iIEL the presence of the Fc epsilonRI gamma chain could be accounted for by the surface expression of the Fc gammaRIII(CD16) complex. Because in wild-type (wt) mice only CD16+ iIEL coexpressed Fc epsilonRI gamma and CD3zeta, we concluded that the presence of Fc epsilonRI gamma was dictated by its required participation of CD16 complex. CD8alpha alpha+ iIEL bearing CD16 and B220 were also detected in the intestinal mucosa of RAG-2(null) mice from 12 days after birth onward. Two independent experimental settings were used in an attempt to demonstrate that CD16+ iIEL matured into CD16- T cells. First, in the RAG-2(null) mice, iIEL responded to in vivo administration of an anti-CD3epsilon mAb by progression to a more mature stage of development, characterized by a loss of CD16 and B220. Secondly, a conversion to CD16- iIEL occurred upon transfer of wt CD16+ iIEL into RAG-2(null) mice. We conclude from these experiments that in both RAG-2(null) and wt mice, a precursor/progeny relationship may exists between CD16+ B220+ CD8alpha alpha+ and CD16- B220- CD8alpha alpha+ iIEL.
Transposons are important genetic tools for mutation studies and for location of genes in prokaryotes. However, very little published work is available on transposon mutagenesis in Gluconobacter oxydans. We report here Tn5-induced mutation in a keto acid-producing strain of G. oxydans ATCC 9937 with special reference to the direct-glucose oxidation pathway operative in this organism. In this study, a mutant deficient in glucose dehydrogenase (GDH) activity has been developed by Tn5 mutagenesis. The data of plasmid profiles in the wild-type and the GDH- mutant are indicative of transposition in the first instance on one of the three plasmids (pVJ1) harboured by the organism, resulting in rearrangement of the plasmid and finally stable transposition of Tn5 on the main genome. The final location of Tn5 on the genome has been established by DNA hybridisation studies.
Endothelin (ET) is a potent peptide mediator exhibiting a wide variety of effects in both the parenchymal and nonparenchymal hepatic cells. In the Kupffer cell, ET activates several transmembrane signaling pathways to generate numerous second messengers including the phospholipase C-generated products inositol-1,4,5-trisphosphate and diacylglycerol and the cyclooxygenase product prostaglandin E2 via specific ETB-type receptors. In addition to these findings, we have now demonstrated that endothelin stimulates the production of nitric oxide (NO) in the Kupffer cell in a time- and concentration-dependent manner. Western blot analysis indicates that ET-stimulated NO production occurs though activation of the inducible form of the nitric oxide synthase enzyme. These findings have important implications as the stimulation of NO production by ET may be part of the physiological response to inflammation or infection. Elevated levels of ET and NO have been found to be associated with numerous hepatic pathophysiological conditions that may contribute to derangements in the vascular system seen in these conditions.
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The Hyp mouse, a model for human X-linked hypophosphatemia (XLH), is characterized by phosphate wasting and defective mineralization. Since osteopontin (OPN) is considered pivotal for biological mineralization, we examined the biosynthesis of OPN in osteoblasts of +/Y and Hyp/Y mice. Immunoprecipitation analyses using a specific antibody to OPN revealed that Hyp/Y and +/Y osteoblasts secrete similar levels of OPN as determined by [35S]-methionine biosynthetic labeling, but a reduced phosphorylation was noted after 32P-PO4 biosynthetic labeling. Northern blot hybridization analysis of +/Y and Hyp/Y mice osteoblast mRNAs, using a cDNA probe for mouse OPN, revealed no difference in the steady state levels of osteopontin mRNA. Analysis of casein kinase II activity in +/Y and Hyp/Y mice osteoblast, kidney, heart and liver membrane fractions revealed that casein kinase II activity in the Hyp/Y mice osteoblasts and kidney is only 35%-50%, respectively, of that of the +/Y mice tissues. The accumulated data are consistent with a post-translation defect in the Hyp/Y mouse osteoblast which results in the under-phosphorylation of osteopontin and subsequent under-mineralization of bone matrix.
Various factors were analyzed in 80 consecutive children under 16 years who had acute renal failure (ARF), for various prognostic factors. Overall mortality was 42.5%, with significantly higher levels seen in hemolytic uremic syndrome (68%, P < 0.05) and associated with cardiac surgery (90.9%, P < 0.01). Anuria (67.6% vs. 43.5%, P < 0.05), need for dialysis (85.3% vs. 56.5%, P < 0.05), neurological complications (50% vs. 6.3%, P < 0.01), and respiratory complications (35.2% vs. 2.1%, P < 0.01) were significantly higher in nonsurvivors than survivors. Multiple regression analysis showed the presence of neurological and respiratory complications to be poor prognostic factors.
BACKGROUND: Studies of monozygotic and dizygotic twins indicate an important genetic influence on the variability of responsiveness to norepinephrine in superficial human vein. OBJECTIVES: Genetic aspects of variability of alpha1-adrenergic receptor responsiveness to norepinephrine in superficial veins were further investigated by studying the response to norepinephrine in the dorsal hand veins of parents and their children. METHODS: Subjects were healthy nonsmoking adults (n = 24; age range, 40 to 52 years) and their biological children (n = 20; age range, 15 to 26 years) who were free from medications likely to modify vascular tone. Superficial vein responsiveness to norepinephrine was assessed by the linear variable differential transformer technique. The dose of norepinephrine required to constrict superficial vein diameter by 50% from baseline (ED50) was calculated for each subject. Heritability was estimated by standard techniques of regression of mid-parent/child (natural logarithm) ED50 values. RESULTS: ED50 ranged from 5.6 to 254.6 ng/min in the parents and from 7.8 to 242.3 ng/min in the children. Heritability was calculated at 0.88. CONCLUSIONS: These data confirm wide variability in superficial vein responsiveness to norepinephrine. The results confirm a major genetic influence in biological responsiveness of superficial vein to norepinephrine in healthy humans. Heritability of vascular alpha-adrenergic receptor responsiveness may influence vascular regulation during sympathetic stimulation and blockade.
Our specific aim in a 10-year prospective study of 772 Cincinnati firemen (predominantly aged 26 to 46 years) was to determine the prevalence, attributes, and etiology of persistent hypobetalipoproteinemia, defined by entry low-density lipoprotein cholesterol (LDLC) less than 75 mg/dL. A second specific aim was to cross-sectionally assess hypocholesterolemia (defined by total serum cholesterol [TC] < 130 mg/dL) in 1,314 white and 165 black men aged 26 to 46 years in the National Health and Nutrition Examination Survey (NHANES I). The 141 black and 631 white firemen had 4,973 person-years of follow-up time (median, 7.1 yr/man). Of 772 men, 44 (5.7%) had entry LDL levels less than 75 mg/dL; they had a mean follow-up time of 7.3 yr/man. Of these 44 men, there were 12 (1.8% of the cohort) with entry LDLC less than 75 mg/dL, and at least 67% of their follow-up LDLC levels were less than 75. Their mean entry TC and LDLC levels were low (130 and 58 mg/dL), mean triglyceride (TG) was low (63 mg/dL), and mean high-density lipoprotein cholesterol (HDLC) was high (60 mg/dL), LDLC remained at less than 75 mg/dL in 81% of their follow-up samples. Their mean entry and follow-up cholesterol and LDLC did not differ (P > .1, 130 v 133 mg/dL and 58 v 63 mg/dL). Compared with 32 men with entry LDLC less than 75 mg/dL but with less than 87% of follow-up LDLC less than 75 mg/dL, the 12 men with persistently low LDLC had lower mean Quetelet indices and diastolic blood pressure at entry (2.36 v 2.58, P = .056; 73 v 80 mm Hg, P = .03) and on follow-up study (2.45 v 2.69, P = .04; 72 v 79 mm Hg, P = .05). Of 12 men with persistently low LDLC, two had truncated apolipoprotein (apo) B (familial hypobetalipoproteinemia, two had the apo E genotype 2/3, and two had acquired hypobetalipoproteinemia that antedated mortality from melanoma by 9 years and from alcoholism by 2 years. Comparable to white and black firemen aged 26 to 46 years, 2.9% and 3.6% of whom had entry serum TC less than 130 mg/dL, of 1,314 white and 165 black men in the NHANES I study (aged 26 to 46), 1.8% and 3.6% had hypocholesterolemia (entry TC < 130 mg/dL). Daily mean calorie, fat, and protein intake (grams per day) did not differ (P > .05) in men with entry TC less than 130 mg/dL compared with those with TC 130 to 230 or greater than 230 mg/dL. Hypocholesterolemia in white and black men in NHANES I could not be attributed to hypocaloric intake or to protein, fat, or carbohydrate undernutrition. There appear to be racial differences in the prevalence of hypocholesterolemia. Blacks comprised 18% of the firemen's cohort but 42% of those with persistent hypobetalipoproteinemia; among NHANES I subjects, 3.6% of blacks were hypocholesterolemic versus 1.8% of whites. Unless persistent hypobetalipoproteinemia reflects an underlying disease, alcoholism, etc., it is often heritable, and may be associated with a reduced likelihood of coronary heart disease (CHD) and with increased longevity.
Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.
Neonates and older infants are a diverse group of children, quite different from their older counterparts. Adverse drug reactions may have profound immediate, delayed, and long-term implications for their neurologic and somatic development. The intrauterine, neonatal, and infancy periods are the only stages in life in which one is exposed to and affected by drugs administered to another person, the mother. In addition, because of the fragility of the neonate and the complexity of their illnesses, their pharmacotherapy is frequently complicated with misadventure and adverse drug reactions that are unavoidable or difficult to assess. Because of their differences in morphology and disease process and treatments, infants and children experience a different range of adverse drug reactions. These reactions are not necessarily predictable from the adult experience. Despite the advances made in the field of pediatric adverse drug reactions and the lessons learned through the misfortunes involving children, children continue to suffer. Sixty years after the Elixir of Sulfanilamide-Massengill disaster, children continue to be given medications with diethylene glycol in developing countries. Pediatricians, pharmacologists, and others must continue to be vigilant and active in preventing, monitoring, and treating adverse drug reactions in children. Learning from mistakes of the past will improve the health of children by preventing mistakes in the future.