Biomedical subjects

M Reddy

Publications and source records attributed to M Reddy.

At least 19 recordsLinked to original sources

PubMed2006

Agonal period in potential non-heart-beating donors.

The shortage of donor kidneys for renal transplantation is becoming more severe as the gap between the number of patients waiting for renal transplantation and the number of cadaveric organs available continues to widen. Therefore, many centres have started using non-heart-beating (NHB) donors. There was no clear plan for maximal duration of agonal period in Maastricht category NHB donors after withdrawal of treatment in Newcastle. This withdrawal has been audited in retrospect. Our current wait time is now a maximum of 5 hours; however, previously there have been some considerably longer periods. Concern has always been expressed about poor quality with protracted periods. Nonuse in this review of 58 kidneys can be expressed against time: 0 to 2 hours 13%, 2 to 5 hours 33%, and >5 hours 45%. Therefore, though the nonuse rate was significantly different between 0 to 2 hours and >5 hours (P < .05, chi-square), there were 16 transplants performed with kidneys >2 hours and 12 transplanted >5 hours. In conclusion, although good usable kidneys can still be used with protracted withdrawal, there are considerable logistical difficulties with our 5-hour cut-off, which means that one third of potential kidneys will not be utilized.

Heart Arrest↗

PubMed2006

Dual renal transplantation for kidneys from marginal non-heart-beating donors.

Kidneys transplanted from non-heart-beating donors (NHBD) are generally regarded as marginal or extended criteria grafts due to the associated period of warm ischemia. The most prolonged periods occurring in the category II (uncontrolled) donor. This potential for injury can adversely affect the glomular filtration rate (GFR), which in severe cases results in primary nonfunction. Viability testing can identify a group of kidneys that, although unsuitable for solitary transplantation, may be considered for dual transplant. This retrospective study examined a series of 11 dual renal transplants, comparing 3- and 12-month GFR outcome data with 81 single NHBD transplants. The mean GFR at 3 months in the dual group was 47.6 and at 12 months was 48.6. In the single group the GFR at 3 months was 40.6 and at 12 months was 41.9. Thus using viability testing to identify NHBD kidneys suitable for dual transplant appears reliable and predictable.

Follow-Up Studies↗

PubMed2006

Renal transplants from category III non-heart-beating donors with evidence of pre-arrest acute renal failure.

Kidneys transplanted from non-heart-beating donors (NHBDs) have been exposed to varying degrees of ischemic damage after death. Category III donors have invariably been managed, treated, and investigated in a hospital setting prior to arrest and death. Some therefore exhibit evidence of renal dysfunction and even acute renal failure (ARF) before death. Many surgeons would regard a NHBD with pre-arrest evidence of ARF as too marginal for renal transplantation. This retrospective study examines five Maastricht category III NHBD donors with evidence of pre-arrest ARF. We compare 3- and 12-month GFR outcome data from the nine resulting transplants with 40 category III NHBD transplants with normal pre-arrest renal function. The mean GFR at 3 months was 45.4 and 43.8 for the ARF and normal group, respectively. At 12 months the GFR was 42.2 and 44.7 in the ARF and normal groups, respectively. Thus evidence of ARF pre-arrest does not preclude successful category III NHBD renal transplantation.

Acute Kidney Injury↗

PubMed2006

Diabetic donors as a source of non-heart-beating renal transplants.

Due to the organ shortage, many renal transplantation centers attempt to increase the donor pool by using non-heart-beating donors (NHBDs). These kidneys are generally regarded as "marginal" grafts. Many centers do not consider transplantation from an NHBD with a history of diabetes as it is a more suboptimal donor. We began our NHBD program in 1998 and have performed 5 renal transplants from diabetic NHBDs. Viability testing identified kidneys suitable for single or dual transplantation. Although kidneys from brain stem dead donors with diabetes have been used successfully, our data suggested that kidneys from diabetic NHBDs can also be used although we still need long-term results.

Cadaver↗

PubMed2006

Renal graft function after prolonged agonal time in non-heart-beating donors.

To deal with the increasing gap between organ demand and supply for kidney transplantation, many centers have started to use non-heart-beating (NHB) donors. When we initiated our program to utilize kidneys from such donors in 1998, we had no protocol for the maximal agonal period. This however was audited in retrospect. Our current wait time is now a maximum of 5 hours. Concern has been expressed in the past about possible deterioration in the quality of the organs with a protracted agonal time. We aimed in this study to examine the effect of prolonging agonal period on the quality of kidneys retrieved from Maastricht category III donors: A total of 40 kidneys were transplanted from 29 category III donors between 1998 and 2004. Eleven kidneys had donor agonal times of >5 hours; the remainder, agonal times <5 hours. Both groups were matched for donor and recipient factors. The mean glomerular filtration rates at 12 months for <5 hours versus >5 hours agonal time were 43.8 +/- 4.4 versus 49.8 +/- 5.8, respectively (P = .24) and at 24 months, 46.83 +/- 8.99 versus 37.67 +/- 3.85, respectively (P = .24). In conclusion, intermediate graft function is comparable to ones with shorter agonal time, although we await long-term results.

Adult↗

PubMed2006

Inhibition of p38alpha MAPK enhances proteasome inhibitor-induced apoptosis of myeloma cells by modulating Hsp27, Bcl-X(L), Mcl-1 and p53 levels in vitro and inhibits tumor growth in vivo.

Inhibition of p38 kinase blocks the production of tumor-promoting factors in the multiple myeloma (MM) bone marrow microenvironment. Proteasome inhibitors MG132 and bortezomib have been shown to have direct cytotoxic effects on MM cells. We show that a selective inhibitor of p38alpha, SCIO-469, enhances the ability of MG132 and bortezomib to induce the apoptosis of MM cells. Previously, we showed that p38 inhibition with SCIO-469 enhances MM cytotoxicity of bortezomib by inhibiting the transient expression and phosphorylation of Hsp27, a downstream target of p38. Here we show that continued treatment of MM cells with bortezomib leads to a SCIO-469-enhanced downregulation of Hsp27 and to increased MM apoptosis. Furthermore, we show that p38 inhibition enhances the bortezomib-induced MM apoptosis by upregulation of p53 and downregulation of Bcl-X(L) and Mcl-1. In a mouse xenograft plasmacytoma model of MM, we found that inhibiting p38 augments the effects of bortezomib in decreasing MM tumor growth in vivo. Thus, in addition to its role in suppressing an activated MM microenvironment, co-treatment with a p38 inhibitor, such as SCIO-469, may enhance the cytotoxicity of bortezomib by modulating pro-apoptotic and anti-apoptotic factors in MM cells, suggesting great potential for co-therapy.

Administration, Oral↗

PubMed2005

Upregulation of calcium-sensing receptor and mitogen-activated protein kinase signalling in the regulation of growth and differentiation in colon carcinoma.

In the present study, we demonstrate that Ca2+-induced growth inhibition and induction of differentiation in a line of human colon carcinoma cells (CBS) is dependent on mitogen-activated protein (MAP) kinase signaling and is associated with upregulation of extracellular calcium-sensing receptor (CaSR) expression. When CBS cells were grown in Ca2+-free medium and then switched to medium supplemented with 1.4 mM Ca2+, proliferation was reduced and morphologic features of differentiation were expressed. E-cadherin, which was minimally expressed in nonsupplemented medium, was rapidly induced in response to Ca2+ stimulation. Sustained activation of the extracellular signal-regulated kinase (ERK) occurred in Ca2+-supplemented medium. When an inhibitor of ERK activation (10 microM U0126) was included in the Ca2+-supplemented culture medium, ERK-activation did not occur. Concomitantly, E-cadherin was not induced, cell proliferation remained high and differentiation was not observed. The same level of Ca2+ supplementation that induced MAP kinase activation also stimulated CaSR upregulation in CBS cells. A clonal isolate of the CBS line that did not upregulate CaSR expression in response to extracellular Ca2+ was isolated from the parent cells. This isolate failed to produce E-cadherin or undergo growth inhibition/induction of differentiation when exposed to Ca2+ in the culture medium. However, ERK-activation occurred as efficiently in this isolate as in parent CBS cells or in a cloned isolate that underwent growth reduction and differentiation in response to Ca2+ stimulation. Together, these data indicate that CaSR upregulation and MAP kinase signalling are both intermediates in the control of colon carcinoma cell growth and differentiation. They appear to function, at least in part, independently of one another.

Cadherins↗

PubMed2003

Reproducibility of prompts in computer-aided detection (CAD) of breast cancer.

AIM: We evaluated the reproducibility of prompts using the R2 ImageChecker M2000 computer-aided detection (CAD) system. MATERIALS AND METHODS: Forty selected two-view mammograms of women with breast cancer were digitized and analysed using the ImageChecker on 10 separate occasions. The mammograms were chosen to provide both straightforward and subtle signs of malignancy. Data analysed included mammographic abnormality, pathology, and whether the cancer was prompted or given an emphasized prompt. RESULTS: Correct prompts were generated in 86 out of 100 occasions for screen-detected cancers. Reproducibility was less in the other categories of more subtle cancers: 21% for cancers previously missed by CAD, a group that contained more grade 1 and small (<10 mm) tumours. Prompts for calcifications were more reproducible than those for masses (76% versus 53%) and these cancers were more likely to have an emphasized prompt. CONCLUSIONS: Probably the most important cause of variability of prompts is shifts in film position between sequential digitizations. Consequently subtle lesions that are only just above the threshold for display may not be prompted on repeat scanning. However, users of CAD should be aware that even emphasized prompts are not consistently reproducible.

Breast Neoplasms↗

PubMed2003

A comparison of propofol and sevoflurane anaesthesia: effects on aortic blood flow velocity and middle cerebral artery blood flow velocity.

We compared systemic (aortic) blood flow and cerebral blood flow velocity in 30 patients randomly allocated to receive either propofol or sevoflurane anaesthesia. Cerebral blood flow velocity (CBFv) was measured in the middle cerebral artery using transcranial Doppler. Systemic blood flow velocity (SBFv) was measured in the aorta using transthoracic Doppler sonography at the level of the aortic valve. Bispectral index (BIS) was used to measure the depth of anaesthesia. Measurements were made in the awake patient and repeated during propofol or sevoflurane anaesthesia, with BIS measurements of 40-50. The effects of SBFv on CBFv were estimated by calculating the cerebral/systemic blood flow velocity-index (CsvI). A CsvI value of 100 indicating a 1 : 1 relationship between CBFv and SBFv. The results demonstrated that propofol anaesthesia produced a significantly greater reduction in CsvI than did sevoflurane anaesthesia [propofol: 60 (19); sevoflurane: 83 (16), p = 0.009, t-test]. This suggests a direct reduction in CBFv independent of SBFv during propofol anaesthesia. The greater reduction of CBFv occurring during propofol anaesthesia may be due to lower cerebral metabolic demand compared with sevoflurane anaesthesia at comparable depths of anaesthesia.

Adult↗

PubMed2003

Functional and economic outcome following microdiscectomy for lumbar disc herniation in 672 patients.

A retrospective assessment of 809 patients operated on in 1990-1998 was performed. A patient-based outcome questionnaire also was incorporated into the study. The outcome was graded according to the Functional Economic Rating scale. A total of 64% of the patients were relieved of their complaints 3.2-10.2 years (median 6.3 years) after lumbar disc surgery. An excellent outcome, defined as Prolo scale of 9 or 10, was achieved in 55.8%, a good outcome (Prolo scale 7 or 8) in 20.7%, a fair outcome (Prolo scale 5 or 6) in 11.4%, and a poor outcome (Prolo scale of </=4) in 12.1% of the patients. Patients with strenuous occupations had a significantly (P = 0.004) less favorable outcome than patients with less strenuous or sedentary occupations. Criteria for evaluating the results of treating lumbar spinal disorders vary widely. A more universal acceptance of common criteria for judging the outcome of spinal operations should facilitate comparisons among various methods of treatment.

Adolescent↗

PubMed2003

Sociotechnical requirements analysis for clinical systems.

OBJECTIVE: We explore sociotechnical requirements by examining the use of a computerized patient record system in an intensive care unit of a U.S. hospital and present two sociotechnical requirements, awareness and coordination, embedded in the users' work. METHOD: The study is based on observation during seven months of the use of a computerized patient record system in a surgical intensive care unit. During that period semi-formal interviews, informal interviews were held. RESULTS AND CONCLUSIONS: A key step in the design of clinical systems is the development and analysis of requirements. However, traditional requirements analysis is based on a set of assumptions that break down in the highly collaborative, exception-filled clinical domain. Sociotechnical requirement analysis enabled the designers to gather a much richer description of the environment surrounding the computer system, highlighting awareness and coordination, embedded in the users' work.

Cooperative Behavior↗

PubMed2002

Stereotactic radiosurgery for brain metastases from colorectal cancer.

PURPOSE: The development of brain metastases represents an ominous event for patients with colorectal cancer. We evaluated results following stereotactic radiosurgery (SR) for patients with metastatic colorectal cancer to identify efficacy of SR and prognostic factors for survival. METHODS: This is a retrospective study of 60 brain metastases from colorectal cancer in 35 consecutive patients who underwent SR from January 1993 to December 1996. Thirteen patients also underwent additional whole-brain radiation therapy (WBRT). The median dose delivered to the tumor margin was 20 Gray (range 16-28 Gy), in most cases the tumor enclosing the 50% isodose (range 40-60%). Patients were classified into two groups: SR with and SR without WBRT. Univariate and multivariate testing was performed to determine significant prognostic factors. RESULTS: The median survival time was 6 months after SR and 40 months after diagnosis of primary tumor. A Karnofsky performance scale >70 was a significantly favorable prognostic factor in uni- and multivariate testing. Post-SR imaging was evaluated in 32 patients and in 54 cerebral lesions. Local tumor control was revealed in 94% of patients and 96% of treated tumors. Two patients developed local recurrences, and remote brain disease was revealed in five. No patient experienced a new focal neurologic deficit due to SR. The addition of WBRT to SR did not improve survival and local tumor control rates. Distant control rate was borderline in univariate analysis and significantly improved for patients who received additional WBRT in multivariate analysis. CONCLUSION: SR for brain metastases from colorectal cancer results in a high local tumor control rate of 94% associated with few complications and therefore provides patients with a higher quality of their remaining life.

Adult↗

PubMed2002

Microsurgical anterior cervical foraminotomy (uncoforaminotomy) for unilateral radiculopathy: clinical results of a new technique.

BACKGROUND: The authors report the clinical application of a new microsurgical technique. The cervical anterior foraminotomy (uncoforaminotomy), which is used for the surgical treatment of unilateral cervical radiculopathy secondary to posterolateral disc herniations or spondylotic foraminal stenoses. METHOD: Between June 2000 and May 2001, 34 patients (16 men and 18 women with a mean age of 43.8 years, range 29 to 80 years) underwent anterior cervical foraminotomy (uncoforaminotomy) for the treatment of cervical radiculopathy at one or two adjacent levels in the Neurosurgical Department of the University of Vienna. This surgical technique was devised to accomplish direct anterior decompression of the affected nerve root by removing an offending posterolateral sponylotic spur or disc fragment. The nerve root is decompressed from its origin in the spinal cord to the point were it passes behind the vertebral artery laterally. The intervertebral disc of the affected level is maintained in its form and function. Thus, the functioning motion segment is preserved and fusion related sequelae, including graft related complications, graft site complications and the adjacent level disease, are avoided. Prior to its clinical application, anatomical features of the anterior cervical spine were reviewed, and an anatomical morphometric analysis and work-up of the technique was performed in 4 cervical specimens. FINDINGS: The follow-up period varied from two to 17 months with a mean of 8.2 months. The large majority (97%) of patients were pleased with the results of their operation. The relief of neck pain and redicular pain in the affected dermatome was immediate in all patients. Motor-weakness and sensory deficit improved dramatically immediately postoperatively, and improved to normalisation in the majority of patients within 3 to 6 months. Two of the patients sustained an incomplete transient recurrent laryngeal nerve palsy, which fully resolved within two to 4 weeks. One of the patients had a repeat herniation on the second postoperative day, but recovered completely after re-operation and continued to do well at the 6-month follow-up. No permanent surgery related morbidity or associated complications were encountered. INTERPRETATION: The results indicate that this new microsurgical technique is an attractive treatment option for adequate anterior decompression of the cervical nerve root via a minimized approach. It was associated with excellent clinical outcome and a less painful postoperative course, allowing patients an almost immediate return to unrestricted full activity.

Adult↗

PubMed2002

A clinical study of a fibrinogen-based collagen fleece for dural repair in neurosurgery.

BACKGROUND: There is frequently a need for dural grafts to cover defects resulting from retraction, shrinkage, or excision following neurosurgical procedures. Many substances have been tried as possible dural substitution, and different tissues and materials have been evaluated for use in dural repair. METHOD: The authors performed a retrospective review of 288 consecutive neurosurgical procedures using a fibrinogen based collagen fleece (TachoComb), a resorbable mesh of collagen from horse tendons, coated with human fibrinogen, bovine thrombin, bovine aprotinin and riboflavin (for marking the coated side), for dural substitution. The fibrinogen and thrombin imitate the last step of the coagulation cascade. On contact with bleeding wounds or other body fluids the coagulation factors dissolve and a link is formed between the collagen carrier and the wound surface. Thrombin converts fibrinogen into fibrin by splitting off peptides. Aprotinin prevents premature lysis of the fibrin clot by plasmin. FINDINGS: Neither superficial or deep wound infections nor aseptic meningitis were noted. We found good fibrous incorporation of TachoComb into the surrounding normal dura. Postoperative cerebrospinal-fluid (CSF) leaks developed in only five cases, who had to be re-operated, upon as well as one patient with a rebleeding. In another four cases, there was notable subcutaneous cerebrospinal-fluid accumulation without CSF-leak. They required a lumbar cerebrospinal-fluid drainage. INTERPRETATION: We conclude that TachoComb is a valuable alternative to the patients fibrous tissues for dural repair in cases in which autogenous tissues are either unavailable or insufficient for proper reconstruction.

Aprotinin↗

PubMed2002

The complexity of trauma to the cranio-cervical junction: correlation of clinical presentation with Doppler flow velocities in the V3-segment of the vertebral arteries.

BACKGROUND: Trauma to the craniocervical junction (CCJ) encompasses a wide and complex spectrum of injury with an even broader range of clinical presentation, and since trauma to this area borderlines neurosurgical main areas of interest, these relatively rare injuries can be overlooked. In fact, there has been an abundance of documentation in the literature since Sir Charles Bell first reported on a case of occipital condyle fracture in 1817 in which a patient suddenly dropped dead as he turned his head to thank physicians and nurses while leaving the hospital. The death was attributed to compression of the medulla oblongata by a fractured occipital condyle. METHOD: At our department, we have been applying specialized diagnostic procedures in our clinical work-up in the acute and chronic situation of isolated injury to the CCJ as well as polytrauma with CCJ involvement in a total of 33 patients throughout a 3-year period (1997 to 2000). In this article, we present some of our experiences with these diagnostic procedures, introducing the application of V3-segment Doppler of the vertebral artery (VA), which we consider to be an effective supplementary method in a precise work-up in CCJ injury. The V3-segment of the vertebral artery, especially where it courses through its' groove behind the superior facet of the atlas is particularly vulnerable to injury. The authors measured flow velocity of the V3-segment from a point just below and roughly 2 to 3 centimeters dorsal to the mastoid process. FINDINGS: All patients were investigated for the occurrence of changes in the blood flow in the V3-segment of the VA after suffering a CCJ injury. There was an increase or decrease in the flow velocity in trauma patients with whiplash injuries as well as in patients with occipital condyle fractures and associated ligament injury. In severe injuries, some with fatal outcome, a dissection or thrombosis of the VA was found with a loss of the V3-doppler flow signal, or rather flow void. CONCLUSION: CCJ injuries in the polytrauma patient as well as in patients presenting with delayed onset of symptoms often remain unrecognised, despite the advances in medicine. CCJ injuries are potentially lethal and can be treated if detected early. The V3 method enables rapid, effective, feasible and inexpensive diagnosis in the initial work-up of CCJ-injury.

Adult↗

PubMed2002

Neurological outcome following laminectomy in spinal metastases.

STUDY DESIGN: Retrospective outcome measurement study. OBJECTIVES: Patients suffering from malignant tumour disease and metastases to the spine develop a variety of clinical complaints including radicular symptoms and/or spinal cord compression syndromes. Palliative decompressive laminectomy with total or partial tumour resection is an acknowledged method of treatment, despite controversy. SETTING: The Department of Neurosurgery of the University of Vienna. METHOD: Patients suffering from metastases with predominant infiltration of the dorsal epidural parts, or patients who could not be operated on via an anterior approach, were included. Eighty-four patients who met these criteria underwent decompressive laminectomy with total or partial tumour removal. The study analyzed motor function, pain relief and continence in a 2- and 4-month post-operative follow-up. According to the criteria of motor performance, 20% of the patients had been mobile pre-operatively. RESULTS: In the immediate post-operative period 45%, after 2 months 33% and after 4 months 26%, were considered mobile. None of the paraplegic patients showed functional improvement. The median survival time was 6.5 months. Pre-operatively, 56% of the patients had shown continence dysfunction. Post-operatively, 38%, and after 2 months 46% of the patients, developed continence disorders. A significant reduction in analgesic medication was also observed in the post-operative period. CONCLUSION: In our series, palliative laminectomy with total or subtotal tumour reduction in patients with malignant spinal metastatic disease resulted in amelioration of motor function, pain and continence and therefore improved the patients' quality of life. The improvement in quality of life shows that this method is a valuable option in neurosurgical therapy, except for cases with pre-operative paraplegia. However, in patients with severe pre-operative paraparesis, the authors recommend laminectomy only in very exceptional cases, because of the poor post-operative neurological results.

Analgesics↗

PubMed2002

Outcome after chronic sciatica as the only reason for lumbar microdiscectomy.

There are only a few long-term studies on microsurgical disc operations, and none concentrated on long-term follow-up of therapy-resistant sciatica. A total of 258 patients whose only neurologic symptoms were sciatica were included in this study. Patients were operated on between 1990 and 1997. All outcome results have been performed by an independent reviewer. The mean follow-up period was 7.3 years (range 4-11 years). At follow-up 25% of the patients were free of pain, 66% demonstrated marked improvement, and 9% had either no improvement or worsening of pain. At follow-up 65% of the patients reported returning to their original occupation or being able to go into retirement without hindrance. A total of 15% required changing of profession following discectomy (75% of these patients applying for early retirement were rejected), 6% were incapacitated and unable to work, and 14% were forced into early retirement. Patients with a history of sciatica longer than 3 months acquired failed back surgery syndrome considerably more often than those <3 months (p = 0.005).

Adult↗

PubMed2001

AtHKT1 is a salt tolerance determinant that controls Na(+) entry into plant roots.

Two Arabidopsis thaliana extragenic mutations that suppress NaCl hypersensitivity of the sos3-1 mutant were identified in a screen of a T-DNA insertion population in the genetic background of Col-0 gl1 sos3-1. Analysis of the genome sequence in the region flanking the T-DNA left border indicated that sos3-1 hkt1-1 and sos3-1 hkt1-2 plants have allelic mutations in AtHKT1. AtHKT1 mRNA is more abundant in roots than shoots of wild-type plants but is not detected in plants of either mutant, indicating that this gene is inactivated by the mutations. hkt1-1 and hkt1-2 mutations can suppress to an equivalent extent the Na(+) sensitivity of sos3-1 seedlings and reduce the intracellular accumulation of this cytotoxic ion. Moreover, sos3-1 hkt1-1 and sos3-1 hkt1-2 seedlings are able to maintain [K(+)](int) in medium supplemented with NaCl and exhibit a substantially higher intracellular ratio of K(+)/Na(+) than the sos3-1 mutant. Furthermore, the hkt1 mutations abrogate the growth inhibition of the sos3-1 mutant that is caused by K(+) deficiency on culture medium with low Ca(2+) (0.15 mM) and <200 microM K(+). Interestingly, the capacity of hkt1 mutations to suppress the Na(+) hypersensitivity of the sos3-1 mutant is reduced substantially when seedlings are grown in medium with low Ca(2+) (0.15 mM). These results indicate that AtHKT1 is a salt tolerance determinant that controls Na(+) entry and high affinity K(+) uptake. The hkt1 mutations have revealed the existence of another Na(+) influx system(s) whose activity is reduced by high [Ca(2+)](ext).

Alleles↗