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Biomedical subjects

M Reddy

Publications and source records attributed to M Reddy.

At least 55 records · Page 3Linked to original sources

Guided bone regeneration of large mandibular defects in a primate model.

BACKGROUND: An earlier publication from our laboratory described the use of guided bone regeneration to fill large bone voids in the mandible created through en bloc resection in primates. The present report is an embellishment of this paper and describes bone regeneration experiments in 18 adult male Macaca mulatta monkeys to determine how long membranes must be in position to promote guided bone regeneration. METHODS: Thirty-six lesions were created in the mandibles of 18 monkeys in a standardized mandibular defect of 8 x 19 mm. Reinforced ePTFE membranes were placed in the animals and held in place with mini screws and sutures for anywhere from 1 to 12 months. No material was added to the defect. In addition to clinical studies, digital subtraction radiology and fluorescent labeling with tetracycline and histomorphometry are described. RESULTS: The results indicate that no bone gain was observed in membranes exposed for 1 month or less, but bone gain (approximately well over 90% of defects) was observed at 12 months when membranes were left in situ for 2 to 12 months (P <0.0001). No significant difference in the amount of bone gained at 12 months was observed for membranes left in place for intervals ranging from 2 to 12 months. A significant correlation between the amount of bone gain observed at 3 and 12 months was observed (P <0.0001). CONCLUSIONS: Data therefore suggest that membranes left in situ for 1 month or less result in minimal bone gain compared with membranes left in place from 2 to 12 months. In addition, labeling and stained sections clearly showed that the bone produced after 2 months of membrane placement is mature.

Animals↗

Myelosarcoma of the cavernous sinus in a nonleukemic patient--case report.

Myelosarcomas are rare, solid extramedullary tumors composed of granulocyte precursors in most cases associated with leukemia. A 38-year-old nonleukemic female presented with a myelosarcoma of the cavernous sinus. After surgical removal of the cavernous sinus tumor she was treated by chemotherapy and whole brain radiation therapy. Despite this aggressive therapy, she died 4 months after surgical intervention.

Adult↗

Participatory design and an eligibility screening tool.

For most medical informatics software products, insufficient effort is spent on the design phase of production. However, poor design often leads to systems that are either not well accepted, or far less effective than they could be. In this paper, we describe the ideas of participatory design and discuss why these ideas are especially applicable to medical informatics systems. In particular, we present a case study in the area of clinical trial protocol management. We designed and developed a tool aimed at increasing accrual to clinical trial protocols at an oncology center. However, the design evolved over time, and features of this design were only discovered through iterative development and interaction with the users within the context of the workplace.

Clinical Protocols↗

Prognostic factor analysis for multiple brain metastases after gamma knife radiosurgery: results in 97 patients.

Stereotactic radiosurgery (SR) is being used with increasing frequency in the treatment of brain metastases. This study provides data from a clinical experience with radiosurgery in the treatment of cases with multiple metastases and identifies parameters that may be useful in the proper selection and therapy of these patients. From January 1993 to April 1997, 97 patients (43 women and 54 men; median age 58 years) suffering from multiple brain metastases (median 3; range 2-4) in MRI scans, received SR with the Gamma Knife. The median dose at the tumor margin was 20 Gy (range 17-30 Gy). Median tumor volume was 3900 cmm (range 100-10,000). Different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness and ataxia had been the predominant neurological symptoms. Major histologies included lung carcinoma (44%), breast cancer (21%), renal cell carcinoma (10%), colorectal cancer (8%), and melanoma (7%). The median survival time was 6 months after SR. The actual one-year survival rate was 26%. In univariate and multivariate analysis, a higher Karnofsky performance rating and absence of extracranial metastases had a significantly positive effect on survival. Local tumor control was achieved in 94% of the patients. Complications included the onset of peritumoral edema (n = 5) and necrosis (n = 1). SR induces a significant tumor remission accompanied by neurological improvement and, therefore, provides the opportunity for prolonged high quality survival. We conclude that radiosurgical treatment of multiple brain metastases leads to an equivalent rate of survival when compared to the historic experience of patients treated with whole brain radiotherapy. Patients presenting initially with a higher Karnofsky performance rating and without extracranial metastases had a median survival time of nine months. Each such case should therefore be evaluated based on these factors to determine an optimal treatment regimen.

Aged↗

An unusual management of an open compound depressed skull fracture with venous sinus involvement. A case report.

A neurosurgical management of an open compound depressed fracture perforating the superior sagittal sinus is reported. Undue bleeding from the fracture did not allow a conservative management. The patient had been operated primarily at an outside emergency surgery unit. Profuse uncontrollable bleeding made a tamponade of the sinus necessary for transportation to our neurosurgical department. After reconstruction of the sinus he survived without evidence of a neurological deficit.

Adult↗

Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages.

The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.

Adult↗

Antibodies to TR2 (herpesvirus entry mediator), a new member of the TNF receptor superfamily, block T cell proliferation, expression of activation markers, and production of cytokines.

TR2 (TNFR-related 2) is a recently identified member of the TNFR family with homology to TNFRII. We have demonstrated previously that TR2 mRNA is expressed in resting and activated human T cells and that TR2-Ig partially inhibits an allogeneic mixed leukocyte proliferation response. We now characterize TR2 further by the use of specific mAbs. Flow-cytometry analysis using TR2 mAbs confirmed that resting PBL express high levels of cell surface TR2, and that TR2 is widely expressed on all freshly isolated lymphocyte subpopulations. However, stimulation of purified T cells with either PHA or PHA plus PMA resulted in decreased surface expression within 48 h of activation before returning to resting levels at 72 h. TR2 mAbs inhibited CD4+ T cell proliferation in response to stimulation by immobilized CD3 or CD3 plus CD28 mAbs. Assay of culture supernatants by ELISA showed inhibition of TNF-alpha, IFN-gamma, IL-2, and IL-4 production, which, for IL-2 and TNF-alpha was also confirmed by intracellular cytokine staining. Furthermore, expression of activation markers on CD4+ T cells, including CD25, CD30, CD69, CD71, and OX40 (CD134), was inhibited. TR2 mAbs inhibited proliferation in a three-way MLR, and a response to soluble recall Ag, tetanus toxoid. In conclusion, these results suggest that TR2 is involved in the activation cascade of T cell responses and TR2 mAbs prevent optimal T cell proliferation, cytokine production, and expression of activation markers.

Animals↗

Intraoperative computed tomography guided neuronavigation: concepts, efficiency, and work flow.

Image-guided surgery is currently considered to be of undisputed value in microsurgical and endoscopical neurosurgery, but one of its major drawbacks is the degradation of accuracy during frameless stereotactic neuronavigation due to brain and/or lesion shift. A computed tomography (CT) scanner system (Philips Tomoscan M) developed for the operating room was connected to a pointer device navigation system for image-guided surgery (Philips EasyGuide system) in order to provide an integrated solution to this problem, and the advantages of this combination were evaluated in 20 cases (15 microsurgical and 5 endoscopic). The integration of the scanner into the operating room setup was successful in all procedures. The patients were positioned on a specially developed scanner table, which permitted movement to a scanning position then back to the operating position at any time during surgery. Contrast-enhanced preoperative CCTs performed following positioning and draping were of high quality in all cases, because a radiolucent head fixation technique was used. The accuracy achieved with this combination was significantly better (1.6:1.22.2). The overall concept is one of working in a closed system where everything is done in the same room, and the efficiency of this is clearly proven in different ways. The most important fact is the time saved in the overall treatment process (about 55 h for one operating room over a 6-month period). The combination of an intraoperative CCT scanner with the pointer device neuronavigation system permits not only the intraoperative control of resection of brain tumors, but also (in about 20% of cases) the identification of otherwise invisible residual tumor tissue by intraoperative update of the neuronavigation data set. Additionally, an image update solves the problem of intraoperative brain and/or tumor shifts during image-guided resection. Having the option of making an intraoperative quality check at any time leads to significantly increased efficiency, improves the operating work flow because of the closed-system concept, and offers an integrated solution for improved patient work flow and clinical outcome.

Brain Neoplasms↗

The relationship between depressive symptoms and cigarette smoking in US adolescents.

AIMS: Data from the Teenage Attitudes and Practices Survey were analyzed to assess the relationship between depressive symptoms and cigarette smoking. DESIGNS, SETTING, PARTICIPANTS: Nationally representative sample of adolescents interviewed in 1989 and again in 1993. MEASUREMENTS: Prevalence rate and adjusted odds ratio for smoking at follow-up by depressive symptoms status at baseline. FINDINGS: Adolescents with depressive symptoms were more likely than other adolescents to start smoking. CONCLUSIONS: The associations between depressive symptoms and regular smoking appears to be established by adolescence.

Adolescent↗

A comparison of iron absorption in adults and infants consuming identical infant formulas.

Fe absorption was estimated in adults and infants from the erythrocyte incorporation of Fe isotopes added to infant formula. Fe absorption was measured in adults using radioisotopes, and in infants with a stable-isotope technique. In adults, the geometric mean Fe absorption from a ready-to-feed soya formula with its native phytic acid content was 2.4%. This increased to 6.0% (P < 0.05) after almost complete dephytinization. In infants, mean Fe absorption values were 3.9 and 8.7% respectively from the same products (P < 0.05). In adults, mean Fe absorption from a spray-dried soya formula containing 110 mg ascorbic acid/l was 4.1%, increasing to 5.3% (P < 0.05) when ascorbic acid was doubled to 220 mg/l. In infants, mean Fe absorption values were 5.7 and 9.5% (P < 0.05) from the same products. Mean Fe absorption from a milk-based formula was 6.5% in adults compared with 6.7% in infants. All meals in the adult and infant studies were fed using an identical meal size of 217 g. Increasing the meal size threefold in adults did not change fractional Fe absorption. Mean Fe absorption values for each meal were lower in adults than in infants but the relative inhibitory effect of phytic acid and the enhancing effect of ascorbic acid were similar. We conclude that Fe absorption studies in adults can be used to assess the influence of enhancers and inhibitors of Fe absorption in infant formulas fed to infants. Further studies, however, are required to extend these findings to weaning foods and complete meals.

Adult↗

Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells.

A novel (TL1), a recently described (TL2) TNF-like, and three recently described TNF receptor-like (TR1, TR2, TR3) molecules were identified by searching a cDNA database. TL1 and TL2 are type-II membrane proteins. TR2 and TR3 are type-I membrane proteins whereas TR1 appears to be a secreted protein. TL1, TL2, TR2 and TR3 were expressed in hematopoietic cells, whereas TR1 was not. Northern blots hybridized with the cDNA probes revealed multiple forms of RNA as well as inducible expression of TL1, TL2, TR2 and TR3. TL2 and TR3, in particular, were highly induced in activated CD4+ T cells. Radiation hybrid mapping localized TR1 and TL2 to 8q24 and 3q26, respectively, which are not near any known superfamily members. TL1 was mapped to 9q32, near CD30L (9q33) and TR2 and TR3 mapped to the region of chromosome 1 that contains the TNFR-II, 4-1BB, OX40 and CD30 gene cluster at 1p36. Only TR3 in this cluster possesses a death domain. Southern blot analysis revealed the presence of TL and TR genes in different mammalian species. TL2, TR1, TR2 and TR3 were recently described by others as TRAIL/Apo-2L, OPG, HVEM and DR3/WSL-1/Apo-3/TRAMP/LARD, respectively.

Amino Acid Sequence↗

[Influence of postoperative pain therapy on nausea and vomiting].

PROBLEM: Postoperative nausea and vomiting remains an important problem. Many risk factors have been identified; however, the importance of postoperative analgesic technique and patient expectation remain poorly defined. METHODS: We prospectively collected data on postoperative nausea and vomiting (PONV) in four groups of randomly selected patients (n=50 per group) who received either simple analgesics, nurse-administered intravenous morphine (NAA), patient-controlled analgesia (PCA) with morphine or epidural analgesia with bupivacaine and fentanyl. Patients were questioned regarding any past history of PONV or motion sickness, their preoperative expectation of suffering PONV and satisfaction with their antiemetic therapy. RESULTS: The incidence of nausea was higher in both morphine groups P<0.05), women (P<0.05), those less than the median age of their group (P<0.05) and those with a past history of PONV (P<0.05) or motion sickness (P<0.05). Most patients did not expect to experience PONV (19.3%). The incidence of nausea was higher in those expecting to experience PONV than in those not expecting to suffer PONV (P<0.01). Of those who received postoperative antiemetic treatment, 23.6% were dissatisfied or very dissatisfied with their therapy. Few patients received a prophylactic antiemetic drug (15%). CONCLUSIONS: Study results show that patient expectation is a potent predictor of postoperative nausea, a risk factor hitherto ignored in the anaesthetic literature, and that, in the provision of analgesia following major surgery, epidural analgesia is associated with less PONV than intravenous morphine.

English Abstract↗

Relationship between cigarette smoking and health risk and problem behaviors among US adolescents.

OBJECTIVE: To examine whether sociodemographic factors and health risk and problem behaviors explain the prevalence of cigarette smoking among US adolescents. DESIGN: Probability survey. PARTICIPANTS: A nationally representative sample of US adolescents. MAIN OUTCOME MEASURES: Weighted prevalence, adjusted odds ratio (OR), and 95% confidence intervals (CIs) for current smoking status by health risk and problem behaviors. RESULTS: The prevalence of smoking was highest among adolescents who were white, older, and who had a high school education or lived in the Northeast. When we adjusted for sociodemographic factors and health risk and problem behaviors, smoking was associated with marijuana use (OR, 3.7; 95% CI, 2.7-5.1), binge drinking (OR, 2.1; 95% CI, 1.6-2.8), and fighting (OR, 1.4; 95% CI, 1.1-1.7) among white adolescent males. Similar associations between each of these 3 behaviors and cigarette smoking were found among white adolescent females and African American and Hispanic adolescent males and females. Cigarette smoking was also associated with using smokeless tobacco, having multiple sexual partners, and not using bicycle helmets among white adolescent males and females, having multiple sexual partners among Hispanic adolescent females, and carrying weapons among Hispanic adolescent males. CONCLUSIONS: Marijuana use, binge drinking, and fighting are correlates of cigarette smoking among US adolescents. These associations, which vary by sex and race or ethnicity, suggest clustering to form a risk behavior syndrome.

Adolescent↗

A primatized MAb to human CD4 causes receptor modulation, without marked reduction in CD4+ T cells in chimpanzees: in vitro and in vivo characterization of a MAb (IDEC-CE9.1) to human CD4.

A Primatized anti-CD4 monoclonal antibody (MAb), CE9.1, with V-domain from cynomolgus macaque (showing 92% homology with human consensus sequence V-domains), and a human IgG1 constant region, was characterized in vitro and in vivo in chimpanzees. This MAb binds human CD4 with Kd of 1.0 nM and was also able to bind to human IgG Fc receptors (Fc gamma R). However, despite being of the IgG1 subclass, CE9.1 did not bind to complement component C1q, nor did it mediate complement-dependent cytotoxicity. Examination of T cells from a number of species showed restricted reactivity for CE9.1, recognizing only human and chimpanzee CD4. In both human and chimpanzee MLRs, it had an IC50 of about 10.0 ng/mL. Therefore, a chimpanzee in vivo model was used to characterize CE9.1, CE9.1 caused transient decrease in the number of lymphocytes bearing the CD4 receptor starting at doses of 0.3 mg/kg in an in vivo dose ranging study in one chimpanzee. This effect was reversed within approximately 7 days. In a multiple high-dose study in which 10.0 mg/kg of CE9.1 was administered at intervals of 1-3 months, there was a dramatic loss of CD4 marker with a reciprocal increase in the number of CD3+ CD8- CD4- cells. The CD4 receptor was totally undetectable on these lymphocytes for 1-2 weeks, with a gradual, but complete, reversal within 4 weeks. We interpret these observations as receptor modulation because, although there was apparent loss of CD4+ lymphocytes, an equivalent number of CD3+CD8- T lymphocytes were present in circulation in all four chimpanzees treated with 10.0 mg/kg CE9.1. Even at this high dose, only limited reduction of CD4+ T lymphocytes was observed in these animals. These observations are in sharp contrast to what has been reported in rodents or in human clinical studies using other IgG1 mAbs to human CD4. CD8 counts, although variable, remained unaffected by CE9.1 treatment. No adverse events were observed following administration of CE9.1 to chimpanzees, and there was no detectable host immune responses to the Primatized MAb.

Animals↗

Influence of intraocular lens haptic material on bacterial isolates from anterior chamber aspirate.

PURPOSE: To determine whether intraocular lens (IOL) type affects the bacterial count in anterior chamber aspirates obtained immediately after cataract surgery. SETTING: L.V. Prasad Eye Institute, Hyderabad, India. METHODS: This in vivo study evaluated two groups of eyes that had uneventful cataract extraction and implantation of one of two types of IOLs: all poly(methyl methacrylate) (PMMA) (n = 73) or polypropylene haptic (n = 83). Anterior chamber fluid aspirates (0.1 mL) were obtained with a 30 gauge cannula at the end of surgery and inoculated onto chocolate agar and in thioglycolate broth. Microbiology evaluation was performed using standard methods. RESULTS: Seven eyes (9.5%) with all-PMMA IOLs and 21 (25.3%) with polypropylene haptic IOLs were positive for bacterial isolates (P = .0322; chi-square test). Mean colony count (+/-SD) was 11.43 +/- 3.78 and 13.16 +/- 4.78 colony-forming units/ milliliter in the PMMA and polypropylene haptic IOL groups, respectively. No eye developed endophthalmitis. CONCLUSION: Polypropylene haptic IOLs were associated with a significant increase in bacteria in the anterior chamber.

Aged↗

A genetic strategy to demonstrate the occurrence of spontaneous mutations in nondividing cells within colonies of Escherichia coli.

A genetic strategy was designed to examine the occurrence of mutations in stationary-phase populations. In this strategy, a parental population of cells is able to survive under both permissive and restrictive conditions whereas mutants at a particular target locus exhibit a conditional-lethal phenotype. Thus, by growing the population to stationary phase under restrictive conditions and then shifting it to permissive conditions, mutations that had arisen in stationary phase can be studied without confounding effects caused by the occurrence of similar mutations during growth of the population. In two different applications of this strategy, we have studied the reversion to Lac+ in stationary phase of several Lac- mutations in Escherichia coli. Our results indicate that a variety of spontaneous point mutations and deletions, particularly those that are sensitive to the mechanisms of replication slippage (for their generation) and methyl-directed mismatch repair (for their correction), can arise in nondividing populations of cells within a colony. The frequency of their occurrence was also elevated in mutS strains, which are defective in such mismatch repair. These data have relevance to the ongoing debate on adaptive or directed mutations in bacteria.

Bacterial Proteins↗

Identification and characterization of ssb and uup mutants with increased frequency of precise excision of transposon Tn10 derivatives: nucleotide sequence of uup in Escherichia coli.

A Lac+ papillation assay was used to identify mutants (tex) of Escherichia coli that exhibit an increased frequency of precise excision of a lacZ::Tn10dKan insertion. Three tex strains had suffered mutations in the gene (ssb) encoding the essential single-stranded DNA-binding protein SSB, which resulted in the following alterations in the 177-residue protein: G4D; L10F, P24S; and V102M. The phenotypes of these ssb mutants indicated that they were largely unaffected in other functions mediated by SSB, such as DNA replication, recombination, and repair. Strains with multicopy ssb+ exhibited a decreased frequency of Tn10dKan precise excision. Three other tex mutants had insertion mutations in the locus designated uup at 21.75 min on the linkage map. The nucleotide sequence of uup was determined, and the gene was inferred to encode a 625-amino-acid hydrophilic protein that belongs to the superfamily of ABC-domain proteins (with two pairs of the Walker A and B motifs), which are postulated to be involved in coupling ATP hydrolysis with other biological processes. The uup gene product shares extensive homology with the deduced sequences of two proteins of Haemophilus influenzae. The uup gene is also situated immediately upstream of (and is transcribed in the same direction as) the paraquat-inducible SoxRS-regulated pqi-5 gene, two reported promoters for which are situated within the uup coding sequence.

ATP-Binding Cassette Transporters↗