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Biomedical subjects

A Krishnan

Publications and source records attributed to A Krishnan.

At least 19 recordsLinked to original sources

Application and assessment of a robust elastic motion correction algorithm to dynamic MRI.

The purpose of this study was to assess the performance of a new motion correction algorithm. Twenty-five dynamic MR mammography (MRM) data sets and 25 contrast-enhanced three-dimensional peripheral MR angiographic (MRA) data sets which were affected by patient motion of varying severeness were selected retrospectively from routine examinations. Anonymized data were registered by a new experimental elastic motion correction algorithm. The algorithm works by computing a similarity measure for the two volumes that takes into account expected signal changes due to the presence of a contrast agent while penalizing other signal changes caused by patient motion. A conjugate gradient method is used to find the best possible set of motion parameters that maximizes the similarity measures across the entire volume. Images before and after correction were visually evaluated and scored by experienced radiologists with respect to reduction of motion, improvement of image quality, disappearance of existing lesions or creation of artifactual lesions. It was found that the correction improves image quality (76% for MRM and 96% for MRA) and diagnosability (60% for MRM and 96% for MRA).

Adult↗

Direct space-to-time pulse shaper with reflective arrayed waveguide gratings and phase masks.

We demonstrate for what we believe to be the first time the generation of sequences of ultrafast optical pulses by phase modulation in a direct space-to-time pulse shaper. The pulse shaper is based on the combination of a reflective arrayed waveguide grating multiplexer and an external reflector. The spatial modulation of the phase was obtained by fabricating corrugated patterns on the external reflector. We demonstrate that pulse sequences with different repetition rates can be obtained by changing the period in the patterned mask.

Journal Article↗

Maintenance thalidomide following single cycle autologous peripheral blood stem cell transplant in patients with multiple myeloma.

Although autologous stem cell transplant is an effective therapy for patients with multiple myeloma and extends progression-free survival (PFS) and overall survival (OS), patients show a continued pattern of recurrent disease. Twenty-nine patients were enrolled in a phase II study investigating the tolerability and efficacy of maintenance thalidomide following single autologous peripheral blood stem cell transplant. Six to eight weeks after transplant, patients were started on maintenance thalidomide at 50 mg a day. The dose was gradually escalated to a target dose of 400 mg a day and continued until disease progression or 6 months after achieving complete remission (CR) for a maximum total duration of 18 months. At 6 months, 13 patients (45%) achieved CR or near complete remission (positive immunofixation without any evidence of disease). The estimated 2-year OS was 83% and PFS was 49%. Median tolerated dose of thalidomide was 200 mg a day. In conclusion, thalidomide as maintenance therapy is feasible and may improve outcome after single autologous stem cell transplant.

Aged↗

Modified Ilizarov technique for infected nonunion of the femur: the principle of distraction-compression osteogenesis.

PURPOSE: To evaluate the treatment outcome of the modified Ilizarov technique in infected nonunion of the femur. METHODS: Between 1989 and 2002, records of 20 patients with infected nonunion of the femur treated with the modified Ilizarov technique were retrospectively reviewed. The modified Ilizarov frame was fixed after necrectomy of the dead infected bone and tissues. A proximal or distal corticotomy was performed following biological principles. For regeneration of gap, segmental transport was performed in 11 patients with a gap of more than 5 cm; acute docking followed by lengthening at the corticotomy site was performed in 9 patients with a gap of smaller than 5 cm. Mobilisation was started early with active participation of the physical therapist and the patients. Bone and functional results were measured and complications were categorised according to the Association for the Study and Application of the Method of Ilizarov guidelines. RESULTS: The mean follow-up period was 62.8 months. Bony union and eradication of the infection was achieved in all patients except one who underwent amputation due to uncontrolled infection. Bone results were excellent in 13 patients, good in 4, fair in one, poor in one, and treatment failure (amputation) in one. Functional results were excellent in 3 patients, good in 9, fair in 3, poor in 4, and failure in one. A total of 71 complications occurred: 35 problems, 6 obstacles, and 30 true complications. The mean healing index was 38.3 day/cm (standard deviation, 1.6 day/cm). CONCLUSION: The Ilizarov technique is a good salvage operation for infected nonunion of the femur. Limb salvage is preferable to prosthesis if the limb is viable, adequately innervated and the patient is mentally and financially committed to save the limb.

Adolescent↗

Involvement of private practitioners in tuberculosis control in Ballabgarh, Northern India.

SETTING: The Revised National Tuberculosis Control Programme (RNTCP) in India covered 70% of the population in 2003. However, the private sector, where a large proportion of tuberculosis (TB) patients are seen, does not have sufficient involvement in the programme. OBJECTIVE: To test the feasibility of involving private practitioners (PPs) in the RNTCP for identification and management of TB cases. DESIGN: PPs in Ballabgarh Block, Haryana, were identified and invited for training in RNTCP guidelines. They referred TB suspects for confirmation of diagnosis to a nearby public facility. Patients could subsequently choose to return to their referring doctor or to the government facility. Patients and doctors were interviewed at the end of the project to assess their perceptions. RESULTS: Of 146 PPs, 72% were trained in RNTCP guidelines and 14 agreed to provide directly observed treatment (DOT). During the study period (May 2001-December 2003) 113 patients initiated treatment, leading to an incremental gain of 11.5% in case finding. The cure rate among the 113 sputum positive patients was 73%, and the default rate was 11.5%. CONCLUSION: Involvement of private practitioners in TB control is possible and results in benefits for all stakeholders.

Communicable Disease Control↗

CT arteriography and venography in pulsatile tinnitus: preliminary results.

BACKGROUND AND PURPOSE: Pulsatile tinnitus (PT), a common disorder, can be caused by a variety of otologic and vascular lesions. Various imaging modalities, including CT, MR imaging and angiography, and conventional angiography, have been used in the assessment of PT. Ideally, a single imaging study to evaluate for the largest variety of etiologies would be optimal. In our study, we examine the potential for CT arteriography and venography (CTA/V) in the evaluation of PT. METHODS: Sixteen patients with PT were prospectively evaluated by an otolaryngologist, had a normal otologic examination, and were referred for a CTA/V. All examinations were performed on a 16-section multidetector CT. The carotid bifurcations, internal carotid artery course, transverse and sigmoid sinuses, jugular foramen, internal jugular vein, sella turcica, and temporal bones were evaluated. RESULTS: Seven of the 16 patients had lesions on CTA/V that could account for their PT. Examples of pathologic conditions in the series included a significantly dominant venous system, a venous diverticulum with stricture, and a transverse sinus stenosis. CONCLUSIONS: Preliminary findings indicate that CTA/V can be a valuable imaging tool in the assessment of PT. With this technique, arterial, venous, middle, and inner ear causes of PT can be excluded.

Adult↗

Robust pulmonary nodule segmentation in CT: improving performance for juxtapleural cases.

Two novel methods are proposed for robust segmentation of pulmonary nodules in CT images. The proposed solutions locate and segment a nodule in a semi-automatic fashion with a marker indicating the target. The solutions are motivated for handling the difficulty to segment juxtapleural, or wall-attached, nodules by using only local information without a global lung segmentation. They are realized as extensions of the recently proposed robust Gaussian fitting approach. Algorithms based on i) 3D morphological opening with anisotropic structuring element and ii) extended mean shift with a Gaussian repelling prior are presented. They are empirically compared against the robust Gaussian fitting solution by using a large clinical high-resolution CT dataset. The results show 8% increase, resulting in 95% correct segmentation rate for the dataset.

Algorithms↗

Cerebral venous and dural sinus thrombosis in severe falciparum malaria.

Common causes of coma in falciparum malaria are cerebral malaria, hypoglycaemia and electrolyte disturbances. Focal deficits due to arterial infarcts may sometimes occur in children, but are rare in adults. Three adults with falciparum malaria who had fever, altered consciousness and focal neurological deficits (one of whom also had seizures) are being reported here. CT scan of the brain revealed haemorrhagic infarction of the cerebral cortex and subcortical white matter with surrounding oedema suggestive of venous infarction in all three patients. The diagnosis of cerebral venous thrombosis was missed in the first patient, and was detected only at autopsy. In the next two patients, superior sagittal sinus thrombosis was confirmed angiographically. Only one patient survived; the other two died of increased intracranial pressure. Two of the three patients also had Plasmodium vivax co-infection. A hypercoagulable state resulting from severe malaria may be responsible for this rare and potentially fatal complication. Cerebral malaria may be associated with raised intracranial pressure due to cerebral oedema. Cerebral venous thrombosis may worsen this and adversely affect outcome. This diagnosis should be suspected in patients with severe malaria who develop focal neurological deficits and confirmed by appropriate imaging; judicious use of local thrombolytic therapy may help improve outcome.

Adult↗

Benzathine penicillin, metronidazole and benzyl penicillin in the treatment of tetanus: a randomized, controlled trial.

Penicillin, the drug of choice in tetanus, may potentiate the effect of tetanus toxin by inhibiting the type-A (GABAA) receptor for gamma-amino-n-butyric acid. Metronidazole has therefore been suggested as an alternative. Intramuscular benzathine penicillin (1.2 million units as a single dose; N=56), enteral metronidazole (600 mg every 6 h for 10 days; N=55) and intravenous benzyl penicillin (2 million units every 4 h for 10 days; N=50) were therefore compared, in a randomized, controlled trial, among patients with all grades of tetanus. On presentation, the three treatment groups were similar in terms of age and sex distributions, immune statuses, durations of illness, and their APACHE-II scores and Ablett's grades of tetanus. Of the patients given benzathine penicillin, 36 required tracheostomy, 10 neuromuscular blockade, and 23 mechanical ventilation; the corresponding numbers for the metronidazole (34, 12 and 18, respectively) and benzyl-penicillin groups (39, 12 and 25, respectively) were similar (P>0.10). The incidences of dysautonomia and nosocomial pneumonia and the numbers of in-hospital deaths (26 with benzathine penicillin, 19 with metronidazole and 22 with benzyl penicillin; P=0.392) were also similar in each treatment arm. The length of the hospital stay was longer in the patients receiving benzyl penicillin than in the benzathine-penicillin or metronidazole groups, with means (S.D.) of 21.9 (15), 16.9 (11) and 19.9 (15) days, respectively, but the difference was not statistically significant (P=0.09). Although the three antibiotic regimens investigated appear equally effective, benzathine penicillin offers the convenience of a single, intramuscular injection instead of the 10 days of therapy needed with the other two drugs.

Adult↗

A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome.

The prognosis of patients with primary refractory acute myelogenous leukemia (AML) is poor. Our initial report suggested that some patients could achieve durable remission after allogeneic stem cell transplantation (SCT). Herein, we update our initial experience and report further analysis of this group of patients to determine whether there are pre-SCT prognostic factors predictive of posttransplantation relapse and survival. We reviewed the records of 68 patients who consecutively underwent transplantation at the City of Hope Cancer Center with allogeneic SCT for primary refractory AML between July 1978 and August 2000. Potential factors associated with overall survival and disease-free survival were examined. With a median follow-up of 3 years, the 3-year cumulative probabilities of disease-free survival (DFS), overall survival (OS), and relapse rate for all 68 patients were 31% (95% confidence interval [CI], 20%-42%), 30% (95% CI, 18%-41%), and 51% (95% CI, 38%-65%), respectively. In multivariate analysis, the only variables associated with shortened OS and DFS included the use of an unrelated donor as the stem cell source (relative risk, 2.23 [OS] and 2.05 [DFS]; P =.0005 and.0014, respectively) and unfavorable cytogenetics before SCT (relative risk: 1.68 [OS] and 1.58 [DFS]; P =.0107 and.0038, respectively). Allogeneic SCT can cure approximately one third of patients with primary refractory AML. Cytogenetic characteristics before SCT correlate with transplantation outcome and posttransplantation relapse.

Adolescent↗

Reduced-intensity allogeneic stem cell transplantation for patients whose prior autologous stem cell transplantation for hematologic malignancy failed.

Autologous hematopoietic stem cell transplantation (autoSCT) is an effective treatment for patients with various hematologic malignancies. Despite the significant improvement in the overall outcome, disease progression after transplantation remains the major cause of treatment failure. With longer follow-up, therapy-related myelodysplasia/acute myelogenous leukemia is becoming an important cause of treatment failure. The prognosis for these 2 groups of patients is very poor. Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potential curative treatment for these patients. However, the outcome with conventional myeloablative alloSCT after failed autoSCT is typically poor because of high transplant-related mortality. In an attempt to reduce the treatment-related toxicity, we studied a reduced-intensity conditioning regimen followed by alloSCT for patients with progressive disease or therapy-related myelodysplasia/acute myelogenous leukemia after autoSCT. This report describes the outcomes of 28 patients with hematologic malignancies who received a reduced-intensity alloSCT after having treatment failure with a conventional autoSCT. Fourteen patients received a hematopoietic stem cell transplant from a related donor and 14 from an unrelated donor. The conditioning regimen consisted of low-dose (2 Gy) total body irradiation with or without fludarabine in 4 patients and the combination of melphalan (140 mg/m(2)) and fludarabine in 24. Cyclosporine and mycophenolate mofetil were used for posttransplantation immunosuppressive therapy, as well as graft-versus-host disease (GVHD) prophylaxis, in all patients. All patients engrafted and had >90% donor chimerism on day 100 after SCT. Currently, 13 patients (46%) are alive and disease free, 7 patients (25%) developed disease progression after alloSCT, and 8 (32%) died of nonrelapse causes. Day 100 mortality and nonrelapse mortality were 25% and 21%, respectively. With a median follow-up of 24 months for surviving patients, the 2-year probabilities of overall survival, event-free survival, and relapse rates were 56.5%, 41%, and 41.9%, respectively. Six patients (21%) developed grade III to IV acute GVHD. Among 21 evaluable patients, 15 (67%) developed chronic GVHD. We conclude that (1) reduced-intensity alloSCT is feasible and has an acceptable toxicity profile in patients who have previously received autoSCT and that (2) although follow-up was short, a durable remission may be achieved in some patients who would otherwise be expected to have a poor outcome.

Adult↗

Should HIV-positive patients with lymphoma be offered stem cell transplants?

Advances in effective antiretroviral therapy for HIV infection have made high-dose therapy and autologous stem cell transplantation possible in patients with HIV-associated lymphomas. Regimen-related toxicity is not significantly increased when antiretroviral therapy is combined with high-dose chemoradiotherapy. Durable engraftment can be seen with autologous stem cell rescue. Infectious complications can be managed with a combination of surveillance and prophylaxis. Long-term remissions of these high-risk lymphomas can be achieved with this approach. This suggests that patients with HIV-associated lymphomas should be considered for autologous transplantation in a manner similar to HIV-negative lymphoma patients.

Antiretroviral Therapy, Highly Active↗

Pseudo-isolated FSH deficiency caused by an inhibin B-secreting granulosa cell tumour: case report.

Isolated FSH deficiency due to a mutation in the FSHbeta subunit is characterized by an extremely low serum FSH concentration. We report a patient who presented with an FSH of 0.8 mIU/ml and infertility associated with anovulation. Endocrinological assessment and immunohistochemistry revealed that a granulosa cell tumour was secreting inhibin B and suppressing FSH; however, LH and estradiol were within their normal ranges. Upon removal of the tumour, inhibin B decreased and FSH levels rose to normal values. The patient subsequently conceived and delivered successfully. Based on this case and on those previously described in the literature, we suggest that inhibin B levels should be evaluated in anovulatory patients having a clinical presentation consistent with functional hypothalamic amenorrhoea and very low to normal values of FSH.

Adult↗

A comparative study of avian auditory brainstem responses: correlations with phylogeny and vocal complexity, and seasonal effects.

We conducted a comparative study of the peripheral auditory system in six avian species (downy woodpeckers, Carolina chickadees, tufted titmice, white-breasted nuthatches, house sparrows, and European starlings). These species differ in the complexity and frequency characteristics of their vocal repertoires. Physiological measures of hearing were collected on anesthetized birds using the auditory brainstem response to broadband click stimuli. If auditory brainstem response patterns are phylogenetically conserved, we predicted woodpeckers, sparrows, and starlings to be outliers relative to the other species, because woodpeckers are in a different Order (Piciformes) and, within the Order Passeriformes, sparrows and starlings are in different Superfamilies than the nuthatches, chickadees, and titmice. However, nuthatches and woodpeckers have the simplest vocal repertoires at the lowest frequencies of these six species. If auditory brainstem responses correlate with vocal complexity, therefore, we would predict nuthatches and woodpeckers to be outliers relative to the other four species. Our results indicate that auditory brainstem responses measures in the spring broadly correlated with both vocal complexity and, in some cases, phylogeny. However, these auditory brainstem response patterns shift from spring to winter due to species-specific seasonal changes. These seasonal changes suggest plasticity at the auditory periphery in adult birds.

Acoustic Stimulation↗

Autologous stem cell transplantation for HIV-associated lymphoma.

Is peripheral stem cell mobilization followed by autologous stem cell transplantation (ASCT) feasible in patients with human immunodeficiency virus (HIV)- associated lymphoma (HIV-L)? Studies have demonstrated that, in the HIV- negative (HIV(-)) setting, ASCT may improve lymphoma-free survival in high-risk non-Hodgkin lymphoma (NHL) or relapsed Hodgkin disease (HD) and NHL. Given the poor prognosis of HIV-L with conventional chemotherapy, this dose-intensive approach was explored. Nine patients with HIV-HD or NHL mobilized a median of 10.6 x 10(6) CD34(+) cells/kg and engrafted after ASCT. CD4 counts recovered to pretransplantation levels and HIV viral loads were controlled in patients compliant with antiretroviral therapy. Seven of 9 patients remain in remission from their lymphoma at a median of 19 months after transplantation. Thus, patients with HIV-L on antiretroviral therapy can engraft following ASCT. Prolonged lymphoma remissions, without significant compromise of immune function, can be seen, suggesting that ASCT can be used in selected patients with HIV-L.

Adolescent↗

Negatively calcium-modulated membrane guanylate cyclase signaling system in the rat olfactory bulb.

The mechanism by which the individual odor signals are translated into the perception of smell in the brain is unknown. The signal processing occurs in the olfactory system which has three major components: olfactory neuroepithelium, olfactory bulb, and olfactory cortex. The neuroepithelial layer is composed of ciliated sensory neurons interspersed among supportive cells. The sensory neurons are the sites of odor transduction, a process that converts the odor signal into an electrical signal. The electrical signal is subsequently received by the neurons of the olfactory bulb, which process the signal and then relay it to the olfactory cortex in the brain. Apart from information about certain biochemical steps of odor transduction, there is almost no knowledge about the means by which the olfactory bulb and cortical neurons process this information. Through biochemical, functional, and immunohistochemical approaches, this study shows the presence of a Ca(2+)-modulated membrane guanylate cyclase (mGC) transduction system in the bulb portion of the olfactory system. The mGC is ROS-GC1. This is coexpressed with its specific modulator, guanylate cyclase activating protein type 1 (GCAP1), in the mitral cells. Thus, a new facet of the Ca(2+)-modulated GCAP1--ROS-GC1 signaling system, which, until now, was believed to be unique to phototransduction, has been revealed. The findings suggest a novel role for this system in the polarization and depolarization phenomena of mitral cells and also contradict the existing belief that no mGC besides GC-D exists in the olfactory neurons.

Animals↗

Solid cancers after bone marrow transplantation.

PURPOSE: To evaluate the incidence and associated risk factors of solid cancers after bone marrow transplantation (BMT). PATIENTS AND METHODS: We analyzed 2,129 patients who had undergone BMT for hematologic malignancies at the City of Hope National Medical Center between 1976 and 1998. A retrospective cohort and nested case-control study design were used to evaluate the role of pretransplantation therapeutic exposures and transplant conditioning regimens. RESULTS: Twenty-nine patients developed solid cancers after BMT, which represents a two-fold increase in risk compared with a comparable normal population. The estimated cumulative probability (+/- SE) for development of a solid cancer was 6.1% +/- 1.6% at 10 years. The risk was significantly elevated for liver cancer (standardized incidence ratio [SIR], 27.7; 95% confidence interval [CI], 1.9 to 57.3), cancer of the oral cavity (SIR, 17.4; 95% CI, 6.3 to 34.1), and cervical cancer (SIR, 13.3; 95% CI, 3.5 to 29.6). Each of the two patients with liver cancer had a history of chronic hepatitis C infection. All six patients with squamous cell carcinoma of the skin had chronic graft-versus-host disease. The risk was significantly higher for survivors who were younger than 34 years of age at time of BMT (SIR, 5.3; 95% CI, 2.7 to 8.6). Cancers of the thyroid gland, liver, and oral cavity occurred primarily among patients who received total-body irradiation. CONCLUSION: The risk of radiation-associated solid tumor development after BMT is likely to increase with longer follow-up. This underscores the importance of close monitoring of patients who undergo BMT.

Adolescent↗

Craniofacial surgery for leaking encephalocele in a newborn baby.

A newborn baby with a leaking frontoethmoidal encephalocele is reported. The 1-day-old baby was referred to our center with a swelling on the nose leaking CSF. The child was the third baby of a consanguinous marriage. The baby had a swelling over the nose, 8 cm in diameter. The center of the swelling looked unhealthy, with a small raw area seeping CSF. CT scan showed a swelling containing tissue isodense with normal brain. The bone window and the 3D CT revealed a basal bone defect in front of the crista galii and an outer bone defect at the frontonasal junction over the nasion. The baby was operated on the 5th day after birth. One-stage repair of the encephalocele was performed, along with correction of hypertelorism and bone grafting over the forehead. The baby withstood the surgery well and was discharged from the hospital on the 10th postoperative day.

Cerebrospinal Fluid↗