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K R Krishnan

Publications and source records attributed to K R Krishnan.

At least 91 records · Page 5Linked to original sources

Memory, language, and praxis in Alzheimer's disease: norms for outpatient clinical trial populations.

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is designed specifically to assess memory, language, and praxis dysfunctions characteristic of Alzheimer's disease (AD). In this report, we use data from 1,648 AD participants in two identical 26-week multicenter drug trials to derive clinical trial population-based norms for ADAS-Cog subtest scores. All 11 ADAS-Cog item scores were sensitive to differences in dementia severity judged either by baseline Mini-Mental State Exam (MMSE) scores or by Global Deterioration Scale (GDS) stage of dementia. Using ADAS-Cog subtest scores alone, 85 percent of GDS 4 subjects and 69 percent of GDS 5 subjects could be classified correctly. In a stepwise discriminant analysis, orientation was the item with the greatest discriminatory power between subjects with GDS 4 and GDS 5 stages of dementia. ADAS-Cog subtest scores also varied by age, gender, educational level, and concurrent use of anti-inflammatory drugs or estrogen (in women). Such normative data may facilitate the selection of appropriate outcome measures to investigate differential treatment effects on specific cognitive domains or in specific AD subpopulations.

Aged↗

A review of racial differences in geriatric depression: implications for care and clinical research.

How racial differences influence depressed elders' seeking and obtaining treatment for depression is poorly understood. Studies in other medical illnesses show older African Americans use fewer health-care services for heart disease, stroke, and renal dialysis. This article reviews the racial composition of Duke University's Clinical Research Center (CRC) for the Study of Depression in the Elderly. Possible explanations for low participation of African Americans in such programs also are discussed. During most of the first year of the CRC project, minority enrollment varied from 5% to 10%, at least one third the African-American population of the area. Active efforts to improve minority recruitment increased this percentage to 15% by the end of the project's second year. Likely explanations for low minority participation rates include 1) elders may recognize depressive symptoms, but do not seek or cannot obtain medical treatment, and 2) depressive symptoms may be attributed to a crisis of the spirit (so help is sought through prayer and the church), the "slowing down" process of aging, or part of life's burden to be endured. Future attempts at both treatment and clinical research recruitment efforts are needed to address these possibilities.

Black or African American↗

Magnetic resonance imaging changes in putamen nuclei iron content and distribution in normal subjects.

To study patterns of iron deposition in the putamen in aging, we reviewed brain magnetic resonance imaging (MRI) scans of 56 normal subjects. We developed the Signal Hypointensity in the Putamen (SHIP) Scale, a semiquantitative measure, to evaluate putamen nuclei for extent of iron deposition relative to the globus pallidus. The SHIP score was highly reliable (kappa = 0.76) and significantly correlated with age (P < 0.0001). We found that age-related iron deposition in putamen nuclei follows a characteristic pattern along a posterolateral-to-anteromedial gradient. This gradient may be related to the microvasculature of the putamen. Other studies are needed to replicate our findings in patients with affective and other neuropsychiatric disorders and to clarify the pathophysiological mechanisms that govern these changes.

Adult↗

MRI morphometric analysis and neuropsychological function in patients with neurofibromatosis.

Volumes of cerebral gray and white matter were measured in 22 children with neurofibromatosis type 1 (NF1) and in 20 controls. Judgment of Line Orientation (JLO) and the Developmental Test of Visual-Motor Integration (DTVMI) were administered to 16 of the NF1 patients. General linear models analysis of covariance revealed significantly larger brain volumes in NF1 children than in controls, particularly in white matter, and particularly in girls. JLO and DTVMI performance were positively related to right-hemisphere gray-matter volume. The results implicate a failure of growth control in NF1, leading to aberrant neurodevelopment. Our findings also suggest a basis for refined understanding of learning disabilities, which are a prominent feature of NF1.

Adolescent↗

Sociodemographic and clinical correlates of number of previous depressive episodes in the depressed elderly.

Age of onset has been used as a correlate of depressive symptomatology in the elderly. Examining frequency of episodes may improve our ability to make such correlations. The authors studied variations in an index presentation of depression in late life based on the number of previous depressive episodes. Having more than two previous episodes (as compared to two or less) was related to younger age, early age of onset, dysthymia, feelings of worthlessness, difficulty concentrating, slowed thoughts, suicidal ideation, generalized anxiety, and decreased perceptions of social support. In a logistic regression model, significant predictors of more than two previous episodes were young age, early age of onset, dysthymia, suicidality, and lower perceived social support. Patients with many episodes may be at higher risk for more severe illness and may require more aggressive treatment.

Aged↗

Nuclear magnetic resonance spectroscopy: new insights into the pathophysiology of mood disorders.

Magnetic Resonance Spectroscopy (MRS) is a novel non-invasive approach for investigation of in vivo brain neurochemistry. In this paper, we review the initial studies conducted in mood disorders. 31P MRS studies have suggested membrane phospholipid and energy metabolism abnormalities in the frontal and temporal lobes of bipolar patients. 1H MRS studies have pointed to increase in choline resonance in the basal ganglia of patients with unipolar and bipolar disorders. Mood disorders are not associated with reductions in N-acetyl-aspartate, unlike schizophrenia and other neuropsychiatric disorders. Both 31P and 1H MRS have begun to be used to investigate the mechanisms of action of ECT. 19F and 7Li MRS offer therapeutically relevant new tools for psychopharmacological investigation, allowing the determination of brain concentrations of psychotropic drugs. Measurement of in vivo brain lithium concentrations may have clinical relevance. While several methodological limitations persist, the noninvasiveness and the unique neurochemical insights provided by MRS offer an excellent opportunity for in vivo investigation of the neurobiology of mood disorders.

Bipolar Disorder↗

Depression in patients with coronary artery disease.

Depression is more prevalent in patients with coronary artery disease (CAD) than in the general elderly population. Although CAD patients with depression have higher mortality rates, depression is often not recognized and treated in these patients. We administered structured psychiatric diagnostic interviews to 99 inpatients with CAD and diagnosed 23% with a major depressive episode (MDE) by DSM-IV criteria. Severity of medical illness and family history of psychopathology were indicators for increased risk for MDE. These findings may facilitate the recognition of CAD patients at greater risk for MDE.

Aged↗

Reproducibility of high spatial resolution proton magnetic resonance spectroscopic imaging in the human brain.

The application of proton (1H) magnetic resonance spectroscopic imaging (MRSI) allows for noninvasive, localized analyses of brain biochemistry; however, minimal work has been devoted to the evaluation of 1H MRSI reproducibility. This study examined the reproducibility of 1H MRSI from five normal subjects on two occasions, separated by 10 days. Reproducibility of the MR signal was evaluated in the context of automated shimming, automated processing, and accurate subject repositioning. Reliability measures for physicochemical indices (choline moieties, creatine, N-acetylaspartate, and myo-inositol) were moderately concordant across repeat studies. Gain variation and repositioning results were excellent. It has been concluded that 1H MRSI reproducibility is adequate for serial studies of brain metabolism.

Adult↗

Imaging in acquired immune deficiency syndrome dementia complex (AIDS dementia complex): a review.

1. Since 1986, the AIDS dementia complex has been recognized increasingly as a significant sequela of HIV infection. Though the pathogenesis remains poorly characterized and the diagnosis is one of exclusion, research utilizing various imaging techniques has resulted in greater understanding of the progressive character of ADC. 2. CT and MR studies have revealed general atrophy, atrophy of the basal ganglia, and white matter lesions that appear to increase in severity with progression of HIV infection. 3. CT and MR are relatively insensitive to the presence of clinical dementia, neurological signs, or positive findings on neuropsychological tests. In addition, they show poor correlation with histopathologic findings. 4. PET, SPECT, and MRS show the greatest sensitivity to changes wrought by primary HIV infection of the CNS and thus the greatest potential for early diagnosis of ADC. 5. PET, SPECT, and MRS show involvement of the basal ganglia, bloodflow abnormalities, and metabolite disturbances in HIV-seropositive subjects without findings on examination or neuropsychological tests.

AIDS Dementia Complex↗

Magnetic resonance imaging of Alzheimer's disease.

1. Although dementia is caused by a heterogeneous group of diseases and pathologic states, Alzheimer's disease is the largest cause, estimated to account for 50 to 75% of all dementias. 2. Unfortunately, confirmation of Alzheimer's disease (AD) requires postmortem histologic confirmation; clinical diagnosis prior to death remains one of exclusion. 3. A large number of structural and volumetric MRI studies have noted anatomic and structural changes accompanying AD, including variable degrees of general cortical atrophy. 4. A classic feature reported by many MRI studies is hippocampal and temporal lobe atrophy. 5. White matter hyperintensities on MRI are common, especially in late onset AD although their significance is still controversial. 6. This article reviews the contribution of magnetic resonance to imaging the neuropathologic changes of AD, discussing both advantages and limitations, and summarizing the major findings.

Alzheimer Disease↗

Epidermal growth factor receptor in the vesical urothelium of paraplegic and tetraplegic patients: an immunohistochemical study.

Spinal cord injury (SCI) patients are at high risk of developing cystitis, and vesical neoplasia. As abnormal growth regulation of urothelium may be a predisposing factor for cystitis and vesical neoplasia, we studied alterations if any, in the expression and localization of epidermal growth factor receptor (EGRF) in the vesical urothelium by an immuno-histochemical technique, using monoclonal mouse anti-human epidermal growth factor receptor antibody (DAKO-EGFRI) in cold-cup biopsies taken from the trigone of the urinary bladder in 18 adult SCI patients who had a neuropathic bladder. Abnormal localisation of EGFR-p, i.e. cytoplasmic, was noted in 13 patients. A linear localization of EGFR-p along the cell membrane of the urothelium, considered as an essential requirement for effective function, was observed in only three cases. Combined cytoplasmic and cell membrane location of EGFR-p was seen in two patients. The three patients with cell membrane location of EGFR-p showed a strong expression of EGFR-p (2+, 2-3+, and 4+, respectively); the intensity of EGFR-p expression in cases of cytoplasmic immunostaining varied considerably. Histopathology revealed denuding cystitis in one; follicular cystitis in four; active inflammatory infiltrate in three; lymphocytic infiltrate in three; squamous metaplasia in six; and intestinal metaplasia in three biopsy specimens. The three specimens showing cell membrane location of EGFR-p were from patients who did not have an indwelling urethral catheter (a paraplegic man practising intermittent self-catheterisation, a tetraplegic patient on penile condom drainage, and a tetraplegic woman with reflex voiding), and histopathology revealed very little inflammatory infiltrate. In contrast, the biopsies from all the nine patients, who were on indwelling urethral catheter drainage and in whom the bladder biopsy revealed varying degree of cystitis, showed only cytoplasmic location of EGFR-p. Similarly, the biopsies from patients with bladder stone (n = 6) showed only cytoplasmic localisation of EGFR-p. In conclusion, abnormalities in vesical urothelial expression in EGFR in SCI patients may play a role in the pathogenesis of cystitis, vesical urothelial metaplasia, dysplasia and neoplasia.

Adult↗

Endoscopic management of urethral trauma in male spinal cord injury patients.

Spinal cord injury (SCI) patients with a neuropathic bladder are more prone to develop catheter-induced urethral trauma than occurs in the general population because many of the SCI patients are on indwelling urethral catheter drainage, or intermittent urethral catheterisation is performed either by them or by their carers. The presenting symptoms of improperly positioned Foley catheter in SCI patients may be at times, peculiar to the SCI patients and these include profuse sweating, bypassing of the catheter, increased spasms, or rarely, full fledged features of autonomic dysreflexia. With the availability of the flexible cystoscope, cystourethroscopy has been performed safely on SCI patients who had sustained catheter-induced urethral trauma, on the bedside, with an immediate, and accurate diagnosis of the extent of urethral trauma, and the presence of urethral false passage(s). Further, flexible cystoscopy has helped to treat the patients with urethral trauma by introducing a flexible tip guide wire under vision into the urinary bladder via the normal urethral channel and subsequently, passing a 12 Fr. Foley catheter over the guide wire, thus avoiding the false passage(s) in the urethra. With this technique, it was possible to avert the need for suprapubic urinary diversion in those SCI patients who had sustained acute urethral trauma. Such endoscopic management of acute urethral trauma in SCI patients is described with illustrative case reports of eight patients seen during a 15 month period.

Cystoscopy↗

Intravenous salbutamol treatment for penile erection arising during cystoscopy of cervical spinal cord injury patients.

Two patients with long-standing tetraplegia after spinal cord injury developed reflex penile erection in the operation theatre. One had not received any anaesthesia, and penile erection occurred after introduction of the cystoscope into the urethra, and also autonomic dysreflexia. Intravenous salbutamol, in a dose of 10 micrograms, produced immediate and persistent penile detumescence and salbutamol-induced fall in blood pressure was of therapeutic value. In the second patient, penile erection occurred during general anaesthesia prior to cystoscopy. Immediate and persistent penile detumescence was achieved with intravenous salbutamol 20 micrograms. There was transient fall of blood pressure which responded to intravenous infusion of 0.9% sodium chloride. Salbutamol-induced fall in blood pressure is of therapeutic value in those spinal cord injury patients who develop, in addition to penile erection, autonomic dysreflexia precipitated by urethral instrumentation, or bladder distension with the irrigating fluid. Intravenous salbutamol is preferable to intra-cavernosal phenylephrine, noradrenaline, metaraminol, and epinephrine, or intravenous ephedrine which are contraindicated in patients with hypertension.

Adrenergic beta-Antagonists↗

Unusual complications of intermittent self-catheterisation in spinal cord injury patients.

Three unusual complications of intermittent self-catheterisation in spinal cord injury patients observed over a period of 30 months are described. (1) Two patients performing intermittent catheterisation with a PVC catheter requiring the use of lignocaine gel to numb the urethra, developed allergic reaction in the form of swelling and erythematous lesions around the external urethral meatus. This rare complication was overcome by switching over to the use of a Lofric catheter instead of a PVC catheter for intermittent catheterisation. (2) Urethral bleeding was observed on three occasions in male paraplegic patients performing intermittent self-catheterisation who had allowed the bladder to become over-distended. Bladder emptying therefore, took nearly 10 min, by which time the Lofric catheter became too sticky in the urethra and required undue force for withdrawal, resulting in trauma to the adherent urethral mucosa and urethral bleeding. By adopting the policy of catheterisation at regular intervals and not allowing the bladder to become distended beyond 450 ml of urine, this complication was never seen again either in these three patients or in any other patient using Lofric catheter for intermittent urethral catheterisation. (3) Failure to drain urine after urethral catheterisation resulting in a panic reaction was observed in a 45 year old woman practising intermittent catheterisation. This unique complication happened because there were no eye holes on the Nelaton catheter.

Adult↗

Nerve fibres in urothelium and submucosa of neuropathic urinary bladder: an immunohistochemical study with S-100 and neurofilament.

Intravesical administration of drugs has been used commonly in spinal cord injury patients to suppress detrusor hyperreflexia (eg oxybutynin, verapamil, terodiline) or, to initiate a micturition reflex (eg 15S 15-methyl prostaglandin F2 alpha, protaglandin E2); however, the response has been variable and sometimes, unpredictable. This prompted us to study the presence of nerve fibres in the vesical urothelium and submucosa in mucosal biopsies taken from the dome and trigone (obtained prior to performing a therapeutic procedure eg, vesical lithotripsy, or a diagnostic cystoscopy) in 47 consecutive, unselected paraplegic/tetraplegic patients with a neuropathic urinary bladder. Nerve fibres were demonstrated by routine immunohistochemical technique using commercially available monoclonal and polyvalent antibodies against S-100 (DAKO A/S, Glostrup, Denmark) and Neurofilament (MILAB, Malmo, Sweden). Biopsy specimens were graded for the presence of nerve fibres on a 0-3 scale for urothelium, and superficial/deep submucosa separately in a blind and randomised manner. Virtually no fibre presence was found in one paraplegic patient and no superficial or single fibres were noted in a tetraplegic patient. Absence of C-fibre hyperplasia (Grade 0) was found in nine cases (paraplegic: 4; tetraplegic: 5); Grade 1 hyperplasia was observed in 17 cases (paraplegic: 4; tetraplegic: 13); Grade 2 hyperplasia was seen in 11 cases (paraplegic: 7; tetraplegic 4); and Grade 3 hyperplasia was noticed in eight cases (paraplegic 3: tetraplegic: 5). The magnitude of C-fibre hyperplasia was not significantly different between paraplegic and tetraplegic patients (chi(2) = 4.64; P = 0.3262). The relationship, if any, between the degree of C-fibre hyperplasia and duration of paralysis was studied by categorising patients as < 5 years, and > 5 years of paralysis. No evidence of single fibre or fibre bundle hyperplasia (Grade 0) was seen in five and six cases, grade 1 hyperplasia in six and 11 cases, grade 2 hyperplasia in two and nine cases, and grade 3 hyperplasia in three and five cases respectively in these two categories of patients. (chi(2) = 1.92; P = 0.58). The possible relationship between C-fibre hyperplasia in the vesical mucosa/submucosa and (i) the vesical response to intravesical drug administration; (ii) the vesical urothelial proliferation arrest; (iii) the electrical stimulation of urinary bladder by implanted electrodes (sacral anterior root stimulator); and (iv) long-term indwelling urethral Foley catheter drainage, are discussed with illustrative case reports. In conclusion, mucosal biopsy and study of nerve fibres in urothelium and submucosa of neuropathic bladder has helped to generate hypotheses on the association between C-fibre hyperplasia and response to intravesical pharmacotherapy and the predictive value of such a study in identifying those patients who are likely to respond to intravesical pharmacotherapy.

Adult↗