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Biomedical subjects

R Rao

Publications and source records attributed to R Rao.

At least 19 recordsLinked to original sources
PubMed2026

Surgical Management of Young Women with High-Risk Breast Cancer Receiving Neoadjuvant Systemic Therapy on the I-SPY2 Trial.

BACKGROUND: Mastectomy rates in women with breast cancer are higher in younger women than in older women. The impact of this more extensive surgery on overall survival (OS) and locoregional recurrence in younger women is unknown, especially after neoadjuvant systemic therapy (NST). This study evaluated surgical management and outcomes of patients aged &#x2264; 45 versus > 45 years enrolled in multicenter NST clinical trial, I-SPY2.0 (NCT01042379, PMID 37325931). METHODS: We conducted a secondary data analysis comparing locoregional treatment in patients aged &#x2264; 45 versus > 45 years with clinical or molecular high-risk clinical stage II-III breast cancer treated from April 2010 to June 2022. Multivariate Cox proportional hazards models were used to evaluate associations between type of breast surgery with OS and locoregional recurrence-free interval by age group and tumor receptor subtype. RESULTS: Of 1737 patients, 698 (40.2%) were aged &#x2264; 45 years. There were no significant differences in patient or tumor characteristics or residual cancer burden distribution between age groups. Although breast-conserving surgery was significantly less common in younger women (36.8% vs 48.5%, p < 0.001), surgery type was not associated with OS or locoregional recurrence-free interval for patients aged &#x2264; 45 years. CONCLUSIONS: Greater extent of breast surgery was not associated with improved outcomes in women aged &#x2264; 45 years. Choice of surgical procedure in the management of breast cancer is multifactorial, but young age alone&#xa0;does not warrant mastectomy following NST.

Breast cancer↗
PubMed2002

The role of carotid stenosis in vascular cognitive impairment.

As the contribution of carotid stenosis to cognitive impairment still remains unclear, neuropsychological function and soft neurological signs were examined in patients aged 65 and over. Twenty-five patients with symptomatic carotid stenosis (CS) of 75% or more were compared with 25 patients with first anterior circulation stroke, 25 with peripheral vascular disease and 25 healthy controls. All patients were assessed using CAMCOG (Cambridge Cognitive Examination), tests examining frontal lobe function (Behavioural Dyscontrol Scale [BDYS], Trail-Making Tests A and B, Controlled Word Association Test) and a scale for primitive reflexes (Frontal Release Signs Scale). Patients with symptomatic CS showed greater global impairment on CAMCOG and more severe impairment in frontal lobe function than controls. Those patients scoring less than 15 on the BDYS were more likely to have experienced transient ischemic attacks (TIA) for 5 or more years. Frontal lobe dysfunction, suicidal thinking and age were all independent predictors of global cognitive impairment. Mean number of frontal release signs was higher in patients with CS than in controls, with a higher proportion of patients showing all release signs except glabellar, paratonia and snout reflexes. The study is limited by small numbers and the absence of brain imaging, but provides some evidence for an association between severe carotid stenosis and neuropsychological impairment. The presence of clinically 'silent' cerebrovascular disease affecting frontal lobe function may be missed in routine clinical practice.

Aged↗
PubMed2002

Eating-related concerns, mood, and personality traits in recovered bulimia nervosa subjects: a replication study.

OBJECTIVE: Limited data suggest that eating-related concerns and behaviors, disturbances in mood, and altered temperament persist following recovery from bulimia nervosa (BN). METHOD: In order to replicate and extend such findings, 11 women who were long-term recovered from BN (>1 year with no binging, purging, or restricting behaviors, normal weight, and regular menstrual cycles) were compared with 15 healthy volunteer women on the Eating Disorders Invertory-2 (EDI-2), the Beck Depression Inventory, the State Trait Anxiety Inventory, and the Multidimensional Personality Questionnaire (MPQ). RESULTS: Compared with the control women, the recovered BN women showed elevated levels of the EDI-2 subscales of Drive for Thinness, Body Dissatisfaction, Ineffectiveness, Perfectionism, and Social Insecurity, greater depression and anxiety, elevated levels of the MPQ Stress Reaction dimension and the higher-order factor of Negative Emotionality, and lower levels of the MPQ Well Being and Closeness dimensions. DISCUSSION: Core eating and weight-related concerns, dysphoric affect, social discomfort, and personality traits indicative of perfectionism persist following long-term recovery from BN.

Adult↗
PubMed2002

Abnormalities of hypothalamic-pituitary-thyroid axis in patients with primary empty sella.

Primary empty sella (PES) is a very frequent neuroradiological finding in the general population, that can induce hypopituitarism. Some studies focused on the association of PES with GH deficiency (GHD) or hypogonadotropic hypogonadism (HH), while data regarding the involvement of hypothalamic-pituitary-thyroid (HPT) axis, despite sporadic reports of central hypothyroidism, or the occurrence of hypoadrenalism (HA) are scanty. In this study, thyroid function and TSH response to exogenous TRH injection (TRH/TSH) were investigated in 43 patients [10 men and 33 women; aged (mean +/- SD), 48+/-12 yr] with PES: 22 patients had total and 21 partial PES. Forty healthy subjects (9 men and 31 women; aged 46+/-12 yr) were enrolled as a control group. Central hypothyroidism was found only in 2/43 cases, whereas one patient showed primary hypothyroidism. In euthyroid patients, mean serum TSH levels were significantly lower than controls (TSH: 1.0+/-0.7 vs 1.4+/-0.6 mU/l, p<0.01) and 79% of them showed abnormal TRH/TSH responses (TRH test was performed in 34 euthyroid patients: 17 cases with total and 17 cases with partial PES), but mean serum free T4 (FT4) and free T3 (FT3) values were not significantly lower than controls (FT4: 15.9+/-0.4 vs 15.0+/-2.1 pmol/l, p=NS; FT3: 5.3+/-1.2 vs 5.8+/-1.5 pmol/l, p=NS). Moreover, no significant differences were evident in mean serum TSH, FT4 and FT3 between patients with total and partial PES (TSH: 1.1+/-0.7 vs 0.9+/-0.8 mU/l, p=NS; FT4: 16.3+/-2.6 vs 15.7+/-2.2 pmol/l, p=NS; FT3: 5.4+/-1.3 vs 5.2+/-0.8 pmol/l, p=NS) and the TRH/TSH peak was impaired or exaggerated/delayed in 9 and 3 patients with total and in 12 and 3 cases with partial PES. No significant differences in the prevalence of abnormal TRH/TSH responsiveness were found between patients with partial or total PES (chi2=1.6, p=NS). Other impairment of pituitary function was detected in 23/43 patients: GHD was present in 15 cases, HH in 11 and central HA in 5 patients. Isolated or combined hypopituitarism was present in 17 and in 6 patients, respectively. In conclusion, pituitary dysfunction is very frequent in patients with PES, but central hypothyroidism occurs rarely. The entity of arachnoid herniation into the sellar fossa does not play a significant role on the degree of HPT axis dysfunction.

Adrenal Insufficiency↗
PubMed2002

Plant-to-plant communication mediating in-flight orientation of Aphidius ervi.

Broad bean plants (Viciafaba) infested by the pea aphid, Acyrthosiphonpisum, play akey role in the in-flightorientation of the parasitoidAphidius ervi, by producing host-induced synomones (HIS). These volatiles are herbivore-specific and are systemically released from insect-free parts of an infested plant, suggesting the existence of an elicitor circulating throughout the plant. This study was designed to investigate whether the plant metabolic changes, leading to HIS biosynthesis and emission, can in some way trigger similar responses in neighboring plants through aerial and/or root communication. Uninfested broad bean plants maintained in the same pot together with plants infested by A. pisum became more attractive towards A. ervi females when tested in a wind-tunnel bioassay. This change was not observed when root contact was prevented among plants that had their aerial parts in close proximity, suggesting that an exudate from the roots of the infested plant may cause the induction of the attractive volatiles in uninfested plants. Broad bean plants grown hydroponically also produce pea aphid induced signals that attract A. ervi. When an intact (uninfested) plant was placed in a hydroponic solution previously used to grow a pea aphid-infested plant, it became attractive to parasitoids, while an intact plant placed in a solution previously used to grow an intact plant did not undergo such a change. These results indicate that plant-to-plant signaling in this tritrophic system may occur at the rhizosphere level and is most likely mediated by a systemically translocated elicitor.

Animals↗
PubMed2002

cDNA microarray analysis of changes in gene expression induced by neuronal hypoxia in vitro.

We used cDNA microarray gene expression profiling to characterize the transcriptional response to exposure of cultured mouse cerebral cortical neurons to hypoxia for 24 hr. Of 11,200 genes examined, 1,405 (12.5%) were induced or repressed at least 1.5-fold, whereas 26 known genes were induced and 20 known genes were repressed at least 2.5-fold. The most strongly induced genes included genes coding for endoplasmic reticulum proteins (Ero1L/Giig11, Sac1p, Ddit3/Gadd153), proteins involved in ubiquitination (Arih2, P4hb), proteins induced by hypoxia in non-neuronal systems (Gpi1, Aldo1, Anxa2, Hig1), and proteins that might promote cell death (Gas5, Egr1, Ndr1, Vdac2). These findings reinforce the importance of endoplasmic reticulum-based mechanisms and of protein-ubiquitination pathways in the neuronal response to hypoxia.

Animals↗
PubMed2002

Perinatal aspects of iron metabolism.

UNLABELLED: Iron sufficiency is critical for rapidly developing fetal and neonatal organ systems. The majority of iron in the third trimester fetus and the neonate is found in the red cell mass (as hemoglobin), with lesser amounts in the tissues as storage iron (e.g. ferritin) or functional iron (e.g. myoglobin, cytochromes). Iron is prioritized to hemoglobin synthesis in red cells when iron supply does not meet iron demand. Thus, non-heme tissues such as the skeletal muscle, heart and brain will become iron deficient before signs of iron-deficiency anemia. Gestational conditions that result in lower newborn iron stores include severe maternal iron deficiency, maternal hypertension with intrauterine growth retardation and maternal diabetes mellitus. Stable, very low birthweight premature infants are also at risk for early postnatal iron deficiency because they accrete less iron during gestation, grow more rapidly postnatally, are typically undertreated with enteral iron and receive fewer red cell transfusions. Conversely, iron overload remains a significant concern in multiply transfused sick preterm infants because they have low levels of iron-binding proteins and immature antioxidant systems. CONCLUSION: The highly variable iron status of preterm infants combined with their risk for iron deficiency and toxicity warrants careful monitoring and support in the newborn and postdischarge periods.

Anemia, Iron-Deficiency↗
PubMed2002

In vitro effects of antibiotics on Brugia malayi worm survival and reproduction.

Recent studies have suggested that intracellular Wolbachia spp. endobacteria are necessary for the reproduction and survival of filarial nematodes. The effects of antibiotics that are active against related bacteria on adult worms and microfilariae (Mf) of Brugia malayi in vitro were investigated. Antibiotics tested were doxycycline (Doxy), tetracycline (Tet), rifampicin (Rif), azithromycin (Azith), and chloramphenicol (Chlor). Doxy, Tet, Rif, and Azith reduced release of Mf by adult female worms. The minimum effective concentrations that reduced Mf release by 50% were 5 microg/ml for Doxy, 20 microg/ml for Tet, 40 microg/ml for Rif, and 100 microg/ml for Azith. The same drugs (at higher concentrations) killed adult worms and Mf. Embryograms showed that Tets blocked embryogenesis in female worms. Electron microscopy (EM) showed that the Tets, Rif, and Azith cleared Wolbachia spp. from adult worms and damaged developing embryos. These studies show that antibiotics active against Rickettsiaceae affect adult B. malayi worms and Mf in vitro. Additional studies will be needed to elucidate the mechanisms of action of these antibiotics on Wolbachia and filarial worms.

Animals↗
PubMed2001

Mining DNA microarray data using a novel approach based on graph theory.

The recent demonstration that biochemical pathways from diverse organisms are arranged in scale-free, rather than random, systems [Jeong et al., Nature 407 (2000) 651-654], emphasizes the importance of developing methods for the identification of biochemical nexuses--the nodes within biochemical pathways that serve as the major input/output hubs, and therefore represent potentially important targets for modulation. Here we describe a bioinformatics approach that identifies candidate nexuses for biochemical pathways without requiring functional gene annotation; we also provide proof-of-principle experiments to support this technique. This approach, called Nexxus, may lead to the identification of new signal transduction pathways and targets for drug design.

Apoptosis↗
PubMed2001

APAP, a sequence-pattern recognition approach identifies substance P as a potential apoptotic peptide.

We have previously described a novel cancer chemotherapeutic approach based on the induction of apoptosis in targeted cells by homing pro-apoptotic peptides. In order to improve this approach we developed a computational method (approach for detecting potential apoptotic peptides, APAP) to detect short PAPs, based on the prediction of the helical content of peptides, the hydrophobic moment, and the isoelectric point. PAPs are toxic against bacteria and mitochondria, but not against mammalian cells when applied extracellularly. Among other peptides, substance P was identified as a PAP and subsequently demonstrated to be a pro-apoptotic peptide experimentally. APAP thus provides a method to detect and ultimately improve pro-apoptotic peptides for chemotherapy.

Amino Acid Sequence↗
PubMed2001

Depression in older people with mild stroke, carotid stenosis and peripheral vascular disease: a comparison with healthy controls.

BACKGROUND: Although depression has a recognised association with stroke, the role of "silent" cerebrovascular pathology associated with carotid stenosis and peripheral vascular disease remains unexplored. METHODS: Four groups of 25 community residents aged 65 and over were recruited, comprising first anterior circulation stroke, carotid stenosis accompanied by transient ischaemic attack, peripheral vascular disease and a non-vascular control group. All participants were interviewed using the Hamilton Rating Scale for Depression [HRSD] (including a modified version) and Geriatric Depression Scale. DSM IV criteria for major depression and measures of handicap, social support and physical illness were also administered. Head computerised tomography (CT) scans were performed on stroke patients to examine the relationship between lesion location and depression. RESULTS: One hundred patients were interviewed. Stroke patients were more likely to live in a nursing home and had less social support than other groups. Mean scores on the modified Hamilton and Geriatric Depression Scales were higher in stroke and carotid stenosis groups than controls. Patients with stroke did not show a higher prevalence of DSM IV major depressive disorder than those with carotid stenosis. There was no relationship between the presence of lesions affecting the frontal/subcortical system and prevalence/severity of depression. LIMITATIONS: Small numbers, mortality of stroke patients in hospital, possible selection bias in the control group and use of a previously unvalidated depression rating scale all limit the study. CONCLUSIONS: A possible role for carotid stenosis in the pathogenesis of depressive disorder is suggested. Larger studies incorporating brain imaging may be required to examine the mechanism of this association more closely. The use of a shorter version of the HRSD in older people with cerebrovascular disease may warrant further exploration.

Aged↗
PubMed2001

Physical and sexual abuse histories in patients with eating disorders: a comparison of Japanese and American patients.

Physical and sexual abuse among patients with eating disorders has been a focus of attention in Western countries, however, there is no study comparing the incidence of these factors in Western and Asian countries. Japanese subjects consisted of 38 patients with anorexia nervosa restricting type (AN-R), 46 patients with anorexia nervosa binge eating/purging type (AN-BP), 76 patients with bulimia nervosa purging type (BN) and 99 controls. Subjects from the USA consisted of 29 AN-R, 34 AN-BP and 16 BN. The Physical and Sexual Abuse Questionnaire was administered to all subjects. Minor sexual abuse such as confronting exhibitionism or being fondled by a stranger tended to be more prevalent among Japanese subjects, while victimization by rape or incest was more prevalent among USA subjects. Conversely, physical abuse history was similarly distributed across each diagnostic subgroup in both countries. Events related to physical abuse, such as an abusive family background, may contribute whether eating disorder patients are restricting or bulimic and regardless of culture.

Analysis of Variance↗
PubMed2001

Neonatal iron nutrition.

Preterm infants are prone to iron deficiency. Their total body iron content at birth is low and gets further depleted by clinical practices such as uncompensated phlebotomy losses and exogenous erythropoietin administration during the neonatal period. Early iron deficiency appears to adversely affect cognitive development in human infants. To maintain iron sufficiency and meet the iron demands of catch-up postnatal growth, iron supplementation is prudent in preterm infants. A dose of 2-4 mg/kg/day is recommended for preterm infants who are fed exclusively human milk. A dose of 6 mg/kg/day or more is needed with the use of exogenous erythropoietin or to correct preexisting iron deficiency. However, due to the poor antioxidant capabilities of preterm infants and the potential role of iron in several oxidant-related perinatal disorders, indiscriminate iron supplementation should be avoided.

Anemia, Iron-Deficiency↗
PubMed2001

Indocyanine green angiography of the anterior segment in patients undergoing strabismus surgery.

BACKGROUND: Anterior segment imaging using fluorescein angiography is only suitable in lightly pigmented irides as the brown pigmentation of the iris masks fluorescein transmission. Indocyanine green (ICG) angiography has excellent penetration of pigment epithelium and, therefore, has potential application in detecting perfusion changes of dark irides after strabismus surgery. METHODS: A prospective study was conducted on patients older than 15 years undergoing strabismus surgery. A fundus camera was focused on the arteriolar tufts of the pupillary margin and 50 mg of ICG (concentration of 12.5 mg/ml) was given intravenously. Images were then obtained at 1 minute intervals of 5 minutes' duration. RESULTS: 45 patients with a mean age of 54.6 years and a mean follow up period of 8.6 weeks were studied. There were 23 patients in the primary surgery group, 11 in the secondary surgery group, and 11 in the staged group. Iris ICG angiograms were successfully performed in all patients. No persistent filling defect was detected in the primary and secondary horizontal recti surgery groups or in the secondary or staged vertical and combined vertical rectus groups 6-8 weeks postoperatively. 57% of both primary vertical and combined vertical and horizontal groups showed defects in the early postoperative phase. Only three cases demonstrated late perfusion defects in this series. CONCLUSION: ICG can detect iris perfusion changes in dark irides after strabismus surgery. Iris reperfusion was achieved in the majority of the cases.

Adolescent↗
PubMed2001

The role of carotid stenosis in vascular cognitive impairment.

The role of carotid stenosis in vascular cognitive impairment was reviewed using Medline, EMBASE, PsychLit and PsychInfo databases using the words "carotid stenosis", "neuropsychological tests" and "endarterectomy". Limited evidence exists for frontal lobe dysfunction associated with carotid stenosis, but there is a lack of systematic and prospective studies carried out in consecutive patients, including appropriate neuropsychological and MRI assessment. Possible pathophysiological processes suggested for cognitive impairment associated with carotid stenosis are suggested; these include chronic ischaemia and lacunar infarction; such mechanisms and resultant pathologies may co-exist in the presence of large-artery atheroma.

Brain Ischemia↗
PubMed2000

The yeast Na+/H+ exchanger Nhx1 is an N-linked glycoprotein. Topological implications.

Nhx1, the endosomal Na(+)/H(+) exchanger of Saccharomyces cerevisiae represents the founding member of a newly emerging subfamily of intracellular Na(+)/H(+) exchangers. These proteins share significantly greater sequence homology to one another than to members of the mammalian Na(+)/H(+) exchanger (NHE) family encoding plasma membrane Na(+)/H(+) exchangers. Members of both subtypes are predicted to share a common organization, with an N-terminal transporter domain of transmembrane helices followed by a C-terminal hydrophilic tail. In the present study, we show that Nhx1 is an asparagine-linked glycoprotein and that the sites of glycosylation map to two residues within the C-terminal stretch of the polypeptide. This is the first evidence, to date, for glycosylation of the C-terminal region of any known NHE isoform. Importantly, the mapping of N-linked glycosylation to the C-terminal domain of Nhx1 is indicative of an unexpected membrane topology, particularly with regard to the orientation of the tail region. Although one recent study demonstrated that certain epitopes in the C-terminal domain of NHE3 were accessible from the exoplasmic side of the plasma membrane (Biemesderfer, D., DeGray, B., and Aronson, P. S. (1998) J. Biol. Chem. 273, 12391-12396), numerous other studies implicate a cytosolic disposition for the hydrophilic C-terminal tail of plasma membrane NHE isoforms. Our analysis of the glycosylation of Nhx1 is strongly indicative of residence of at least some portion of the hydrophilic tail domain within the endosomal lumen. These findings imply that the organization of the tail domain may be more complex than previously assumed.

Asparagine↗