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Biomedical subjects

M Husain

Publications and source records attributed to M Husain.

At least 73 records · Page 4Linked to original sources

Prognostic factors in patients with surgically resected stages I and II non-small cell lung cancer.

BACKGROUND: About one-third to one-half of patients with early stages of non-small cell lung cancer (NSCLC) succumb to their disease. In this study, we attempted to identify prognostic factors that predict outcome in patients with stages I and II NSCLC. METHODS: A retrospective evaluation of 454 patients with surgically resected stages I and II NSCLC was performed to determine the impact of various clinical, laboratory, and pathological factors on patient outcome such as overall survival (OS) and event-free survival (EFS). RESULTS: Patients older than 65 years had shorter EFS and OS than younger patients (p = 0.002). Patients with preoperative hemoglobin less than or equal to 10 g% had shorter EFS and OS compared to patients with a hemoglobin greater than 10 g% (p = 0.001). Expectedly, OS and EFS were shorter in patients with stage II as compared to stage I patients (p < 0.001). In a multivariate analysis, age, hemoglobin level, and stage remain significant predictors for EFS and OS. CONCLUSIONS: Older age, anemia, and higher stage are important prognostic factors in patients with surgically resected stage I and II NSCLC.

Adolescent↗

Autologous porcine heart cell transplantation improved heart function after a myocardial infarction.

OBJECTIVE: Fetal cardiomyocyte transplantation improved heart function after cardiac injury. However, cellular allografts were rejected despite cyclosporine (INN: ciclosporin) therapy. We therefore evaluated autologous heart cell transplantation in an adult swine model of a myocardial infarction. METHODS: In 16 adult swine a myocardial infarction was created by occlusion of the distal left anterior descending coronary artery by an intraluminal coil. Four weeks after infarction, technetium 99m-sestamibi single photon emission tomography showed minimal perfusion and viability in the infarcted region. Porcine heart cells were isolated and cultured from the interventricular septum at the time of infarction and grown in vitro for 4 weeks. Through a left thoracotomy, either cells (N = 8) or culture medium (N = 8) was injected into the infarct zone. RESULTS: Four weeks after cell transplantation, technetium 99m-sestamibi single photon emission tomography demonstrated greater wall motion scores in the pigs receiving transplantation than in control animals (P =.01). Pigs receiving transplantation were more likely to have an improvement in perfusion scores (P =.03). Preload recruitable stroke work (P =.009) and end-systolic elastance (P =. 02) were greater in the pigs receiving transplantation than in control animals. Scar areas were not different, but scar thickness was greater (P =.02) in pigs receiving transplantation. Cells labeled with bromodeoxyuridine in vitro could be identified in the infarct zone 4 weeks after transplantation. Swine receiving transplantation gained more weight than control animals (P =.02). CONCLUSION: Autologous porcine heart cell transplantation improved regional perfusion and global ventricular function after a myocardial infarction.

Analysis of Variance↗

Reaching movements may reveal the distorted topography of spatial representations after neglect.

It has been proposed that patients with spatial neglect fail to respond appropriately toward stimuli opposite their brain lesion because they have an impairment of directing attention. However, a disorder of 'intention' - or movement initiation - has also been demonstrated in this condition. Recently, the paths of neglect patients' reaches have been shown to be abnormally curved, but it is unclear whether this impairment is visual or motor. Here, we show for the first time that reaches to and from identical positions executed by three patients recovering from neglect are significantly more curved to visually defined targets compared to when the same targets are defined proprioceptively. These findings indicate that abnormal hand paths in neglect result from an impairment in the visual representation of space used to guide reaches but without any general failure of spatial representation of target position. Furthermore, the curved hand paths reveal how the topography of that representation is distorted in spatial neglect.

Aged↗

The coordination of bimanual prehension movements in a centrally deafferented patient.

Many everyday tasks require that we use our hands co-operatively, for example, when unscrewing a jar. For tasks where both hands are required to perform the same action, a common motor programme can be used. However, where each hand needs to perform a different action, some degree of independent control of each hand is required. We examined the coordination of bimanual movement kinematics in a female patient recovering from a cerebrovascular accident involving anterior regions of the parietal lobe of the right hemisphere, which resulted in a dense hemianaesthesia of her left arm. Our results indicate that unimanual movements executed by our patient using her non-sensate hand are relatively unimpaired. In contrast, during bimanual movements, reaches executed by our patient using her non-sensate hand show gross directional errors and spatiotemporal irregularities, including the inappropriate coupling of movement velocities. These data are discussed with reference to the role played by limb proprioception in the planning and control of prehension movements.

Aged↗

Unconscious activation of visual cortex in the damaged right hemisphere of a parietal patient with extinction.

Visual extinction is a sign classically associated with right parietal damage. The patient can see a single stimulus presented in the ipsilesional or contralesional visual field, but is characteristically unaware of the same contralesional stimulus during simultaneous stimulation of both fields. The ipsilesional stimulus is said to 'extinguish' the contralesional stimulus from awareness during bilateral stimulation, perhaps due to a pathological bias in attention towards the ipsilesional side. Recent psychophysical evidence suggests that, although extinguished stimuli are not consciously seen, they may undergo residual processing and exert implicit effects on performance. However, the neural structures mediating such residual processing for extinguished stimuli remain unknown. Here we studied the neural activity evoked by an extinguished visual stimulus, using event-related functional MRI (fMRI), in a patient with circumscribed right inferior parietal damage and profound left-sided extinction. Monochrome objects (faces or houses) were presented in the left or right field, either unilaterally or bilaterally on each trial, with the patient indicating by button press whether he saw an object on the left, the right or on both sides. He usually saw only the right object on bilateral trials, yet the fMRI data showed activation of visual cortex contralateral to the extinguished left stimulus on these trials (compared with right-only stimulation), in both striate and early extrastriate areas of the right hemisphere. This activity had a similar location and time-course to that resulting from a single stimulus in the left versus right visual field. Cortical pathways involved in the normal processing of a single seen stimulus can thus still be activated by an unseen, extinguished stimulus after right parietal damage. Comparison of fMRI responses for faces versus houses revealed some category-specific activation for extinguished stimuli in right fusiform regions, but only at low statistical threshold. These results are discussed in terms of theoretical accounts for parietal extinction and, more generally, for the neural substrates of visual awareness.

Aged↗

Distinguishing sensory and motor biases in parietal and frontal neglect.

Left neglect after right-hemisphere damage may involve perceptual and/or motor impairments. Here we discuss the limitations of previous attempts to separate these components, and introduce a new method. Six neglect patients (three with right inferior parietal lesions and three with right inferior frontal lesions) moved their right hand to a target light, which appeared unpredictably on either the left or the right of central fixation. The target appeared alone or with a distractor light in the opposite hemifield. Any directional motoric bias was measured by comparing reaches from a central start position with those for the same visual displays, but starting from the left of both possible targets (thus requiring only rightward reaches) or from the right (requiring only leftward reaches). All patients were slower to initiate reaches to left than right targets from a central start, which could reflect perceptual and/or motor biases. Critically, in the parietal neglect group only, initiation speed for left targets improved when a rightward reach was required to these (from a left start) rather than a leftward reach. This suggests a deficit in programming leftward movements into left hemispace, in addition to any visual impairment, for parietal neglect. A control task confirmed that this effect of start position was due to the associated change in reach direction and not to afferent inputs from the hand as it rested at the start position. Frontal neglect patients were slow to execute reaches to left targets, regardless of movement direction. Right visual distractors slowed visual reaction times to left targets more than vice versa in frontal neglect patients, and likewise for reach execution times in parietal neglect patients, suggesting that visual distractors on the neglected side have less impact. Distractor effects were unaffected by start position in the frontal neglect group (suggesting a perceptual basis), but distractors slowed reach initiation in the parietal neglect group only from left and central starts. Taken together, these findings demonstrate a directional motor component to parietal but not frontal neglect, and suggest that in man the inferior parietal lobe plays a role not only in perception but also in the programming of selective reaches. These conclusions are related to recent single-unit data from the monkey parietal lobe.

Aged↗

Suppressed smooth muscle proliferation and inflammatory cell invasion after arterial injury in elafin-overexpressing mice.

Elastases degrade the extracellular matrix, releasing growth factors and chemotactic peptides, inducing glycoproteins such as tenascin, and thereby promoting vascular cell proliferation and migration. Administration of serine elastase inhibitors reduces experimentally induced vascular disease. The ability to mount an intrinsic anti-elastase response may, therefore, protect against intimal/medial thickening after vascular injury. To investigate this, we showed that wire-induced endothelial denudation of the carotid artery is associated with transient elevation in elastase activity and confirmed that this is abolished in transgenic mice overexpressing the serine elastase inhibitor, elafin, targeted to the cardiovascular system. Ten days after injury, nontransgenic littermates show vessel enlargement, intimal thickening, increased medial area and cellularity, and 2-fold increase in tenascin. Injured vessels in transgenic mice become enlarged but are otherwise similar to sham-operated controls. Injury-induced vessel wall thickening, which is observed only in nontransgenic mice, is related to foci of neutrophils and macrophages, in addition to smooth muscle cells that fail to stain for alpha-actin and are likely dedifferentiated. Our study therefore suggests that a major determinant of the vascular response to injury is the early transient induction of serine elastase activity, which leads to cellular proliferation and inflammatory cell migration.

Animals↗

Short test of semantic and phonological fluency: normal performance, validity and test-retest reliability.

Tests of verbal fluency, whether of Semantic Fluency (SF) or Phonological Fluency (PF), are often used as a standard method of neuropsychological assessment. However, very little normative data, standardized on a UK sample, is available, and little is known about the utility of popularly used 'short-forms' of these tasks. Additionally, very little is known about verbal fluency test-retest reliability. In this report we describe the performance of N = 365 normal participants on a version of SF requiring the generation of exemplars of the category 'animals' and a version of the PF task requiring participants to generate words beginning with the letter 'B'. From this data we have derived a percentile distribution for both tasks. We also addressed the impact of sex, age, years of education and IQ upon both SF and PF performance. No sex differences were found on either the PF or the SF tasks. A significant but small correlation between age and SF, but not PF, was observed. Modest correlations between both years of education and IQ and PF and SF performance were also seen. We also report test-retest reliability scores for performance on both SF and PF tasks. Performance on the longer 'FAS' version was found to correlate highly with scores obtained using just the letter 'B'. This suggests that little additional advantage obtains from administering three-letter versions of PF. An extremely high degree of correlation between SF tasks in which participants are given 1 minute and scores obtained when participants are given 1 minute 30 seconds was also observed. Finally, in order to assist users in deciding whether a changed retest score is due to error measurement or a real effect, we calculated Standard Error of Prediction (SEP) scores.

Adult↗

Ventral foramen magnum meninigiomas.

OBJECT: Ventral foramen magnum meningiomas (VFMMs) are rare lesions that account for more than 3% of all meningiomas. These are among the most challenging of all meningiomas to treat. The authors comprehensively analyzed multiple features in a series of VFMMs. METHODS: A retrospective study was performed of 18 patients who harbored a meningioma in the ventral foramen magnum (mean follow-up period, 40 months) and underwent surgery via a transcondylar approach. Sixteen patients underwent surgery for the first time: 12 underwent gross-total (75%), two near-total (12.5%), and two subtotal (12.5%) tumor removal. The remaining two patients were treated for a recurrent tumor. After obtaining postoperative Karnofsky Performance Scale (KPS) scores at follow up, statistically significant improvement was demonstrated compared with the preoperative scores. The extent of surgery and higher preoperative KPS scores were variables that showed statistically significant favorable influence on outcome. Ninth and 10th cranial nerve deficits were the most common complications contributing to a prolonged hospital stay. There were no perioperative deaths. Four patients died during the follow-up period. The first patient died of multiple myeloma. The second patient, in whom surgery was performed to treat a recurrent tumor, died 3 years after the surgery of new tumor recurrence at the age of 80 years. The remaining two patients died 1.5 and 5 months postsurgery of pulmonary embolus and endocarditis, respectively. CONCLUSIONS: Ventral foramen magnum meningiomas can be radically resected in a majority of patients, with frequent but transient morbidity caused by lower cranial nerve deficits. Radical removal of a recurrent tumor provides a relatively long, stable postoperative course. In patients presenting with a low KPS score a poor prognosis is demonstrated, and early diagnosis and treatment are recommended to avoid it.

Adult↗

Cytodiagnosis of benign and malignant Hürthle cell lesions of the thyroid by fine-needle aspiration biopsy.

Eighty-two Hürthle cell (HC) lesions of the thyroid with cytologic evaluation by fine-needle aspiration biopsy (FNAB) were reviewed. In 17 cases the FNAB was not diagnostic because the fine-needle aspirates (FNAs) were too scanty in cellularity. Among the remaining 65 lesions, there were 45 HC adenomas (HCAs), six non-neoplastic HC nodules (NHCNs), 10 primary HC carcinomas (HCCs), and four metastatic HCCs. Forty-four HCAs were diagnosed as HC tumor (HCT), and one HCA was wrongly diagnosed as medullary carcinoma. All six NHCNs were wrongly diagnosed as HCT. Of 10 primary HCCs, there were diagnosed as HCT and seven as suspected HCC. Four metastatic HCCs were correctly diagnosed. The FNAs from 38 HCAs and four NHCNs were predominantly composed of large monomorphic HCs with oval nuclei, inconspicuous nucleoli, and abundant, well-defined, granular cytoplasm present singly, in acinar arrangement, and in monolayered sheets of variable sizes. Nuclear pleomorphism and prominent nucleoli were noted in seven HCAs and two NHCNs. Occasional small syncytial tumor cell clusters (STCCs) were noted in six cases, and a few naked tumor cell nuclei (NTCN) were observed in 16 cases. The FNAs from 14 HCCs were hypercellular. In all cases tumor cells were relatively small and showed monomorphic or pleomorphic nuclei, prominent nucleoli, and ill-defined cytoplasm. STCCs of variable sizes were present in abundance in 10 cases, and numerous NTCN were noted in 12 cases. In two HCCs, the tumor cells with well-defined cytoplasm were present singly and in cohesive sheets, and no STCCs or NTCN were observed. Thus, the presence of small tumor cells with ill-defined cytoplasm and prominent nucleoli in syncytial clusters and abundant NTCN in the FNA of a thyroid nodule should alert the observer about the strong possibility of an HCC.

Adenoma, Oxyphilic↗

Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability.

OBJECTIVES: We investigated whether glutathione (GSH), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion and NO activity in atherosclerosis. BACKGROUND: Endothelial dysfunction and reduced NO activity are associated with atherosclerosis and its clinical manifestations such as unstable angina. METHODS: In the femoral circulation of 17 patients with atherosclerosis or its risk factors, endothelium-dependent vasodilation with acetylcholine (ACH), and endothelium-independent vasodilation with nitroglycerin and sodium nitroprusside were studied before and after GSH. In 10 patients, femoral vein plasma cyclic guanylate monophosphate (cGMP) levels were measured during an infusion of ACH before and after GSH. Femoral artery flow velocity was measured using a Doppler flow wire and the resistance index (FVRI) calculated as mean arterial pressure divided by flow velocity. RESULTS: Glutathione strongly potentiated ACH-mediated vasodilation; at the two doses, FVRI decreased by 47% and 56% before, and by 61% and 67% after GSH (p = 0.003). Glutathione also elevated cGMP levels in the femoral vein during ACH infusion from 17.6 +/- 3 to 23.3 +/- 3 pmol/ml (p = 0.006). Augmentation of ACH responses was only observed in patients with depressed endothelial function. Glutathione did not influence endothelium-independent vasodilation with either NO donor. CONCLUSIONS: Thiol supplementation with GSH selectively improves human endothelial dysfunction by enhancing NO activity.

Acetylcholine↗

Targeted overexpression of elafin protects mice against cardiac dysfunction and mortality following viral myocarditis.

Serine elastases degrade elastin, stimulate vascular smooth muscle cell migration and proliferation, and are associated with myocardial damage. To evaluate the impact of elastase inhibition on cardiovascular development and disease, transgenic mice were created in which the mouse preproendothelin-1 promoter was used to target elafin overexpression to the cardiovascular system. To distinguish the transgene from endogenous elafin, constructs were made incorporating a FLAG sequence; the COOH-terminus FLAG-tagged elafin construct produced a stable, functionally active gene product and was used to create transgenic mice. Consistent with endothelin expression, abundant elafin mRNA was observed in transgenic F1 embryos (embryonic day 13.5) and in adult transgenic mice heart, trachea, aorta, kidney, lung, and skin, but not in liver, spleen, and intestine. Functional activity of the transgene was confirmed by heightened myocardial elastase inhibitory activity. No tissue abnormalities were detected by light microscopy or elastin content. However, injection of 10 plaque-forming units (PFU) of encephalomyocarditis virus resulted in death within 11 days in 10 out of 12 nontransgenic mice compared with one out of nine transgenic littermates. This reduced mortality was associated with better cardiac function and less myocardial inflammatory damage. Thus, elafin expression may confer a protective advantage in myocarditis and other inflammatory diseases.

Animals↗

Motor role of human inferior parietal lobe revealed in unilateral neglect patients.

The exact role of the parietal lobe in spatial cognition is controversial. One influential hypothesis proposes that it subserves spatial perception, whereas other accounts suggest that its primary role is to direct spatial movement. For humans, it has been suggested that these functions may be divided between inferior and superior parietal lobes, respectively. In apparent support of a purely perceptual function for the inferior parietal lobe (IPL), patients with lesions to this structure, particularly in the right hemisphere, exhibit unilateral spatial neglect (deficient awareness for the side of space opposite to that of their lesion). Here we show that patients with right IPL lesions also have a specific difficulty in initiating leftward movements towards visual targets on the left side of space. This motor impairment was not found in neglect patients with frontal lesions, contrary to previous proposals that motor aspects of neglect are particularly associated with anterior damage. Our results suggest that the human IPL operates as a sensorimotor interface, rather than subserving only perceptual functions.

Cerebrovascular Disorders↗

Saccadic eye movement and working memory deficits following damage to human prefrontal cortex.

A patient with a lesion confined largely to the right inferior frontal gyrus was found to be impaired on tests of spatial working memory and executive functioning. By contrast, his pattern recognition was good. The patient's selective impairments are consistent with the view that prefrontal cortex contributes to processes involved in spatial working memory. The patient was also tested on a range of oculomotor paradigms, some of which required the temporary suppression of a saccadic response. He was unable to suppress making contra- or ipsilesional reflexive glances to peripheral stimuli on the "anti-saccade" paradigm, but his performance improved on delayed saccade, memory-guided saccade and fixation tasks. Although reflexive glances were observed under these conditions they occurred more frequently in response to contralesional stimuli than ipsilesional ones. Furthermore, the patient had no difficulty in performing anti-point movements with his ipsilesional hand. Thus, his inability to suppress reflexive glances on the anti-saccade task is not due to a generalised problem of "distractibility". The patient's deficits are discussed in terms of models of anti-saccade generation and are related to recent findings regarding the role of prefrontal cortex in working memory and visual attention.

Attention↗

Maintaining internal representations: the role of the human superior parietal lobe.

In sensorimotor integration, sensory input and motor output signals are combined to provide an internal estimate of the state of both the world and one's own body. Although a single perceptual and motor snapshot can provide information about the current state, computational models show that the state can be optimally estimated by a recursive process in which an internal estimate is maintained and updated by the current sensory and motor signals. These models predict that an internal state estimate is maintained or stored in the brain. Here we report a patient with a lesion of the superior parietal lobe who shows both sensory and motor deficits consistent with an inability to maintain such an internal representation between updates. Our findings suggest that the superior parietal lobe is critical for sensorimotor integration, by maintaining an internal representation of the body's state.

Body Image↗

Role of in vivo proton magnetic resonance spectroscopy in the diagnosis and management of brain abscesses.

OBJECTIVE: In vivo proton magnetic resonance spectroscopy was performed for 24 patients with pyogenic brain abscesses, to examine the consistency of the spectral patterns and to observe the changes in metabolites with treatment. METHODS: Localized proton spectra were obtained from 4- to 8-ml volumes in the abscesses, using stimulated echo acquisition mode and spin echo sequences. Twenty-two patients were treated with combined surgical and medical therapy, and two patients were treated conservatively. High-resolution magnetic resonance spectroscopy was performed for 15 samples of abscesses obtained from these patients, to confirm the assignments of resonances seen in vivo. Postaspiration studies were performed for 12 patients treated with combined medical and surgical therapy and 2 patients treated medically. RESULTS: Lactate and amino acids were seen in spectra for all patients, irrespective of the time of spectroscopy after the onset of combined medical and surgical therapy. Acetate and pyruvate disappeared after 1 week of combined treatment. CONCLUSION: It was concluded that spectral patterns for brain abscesses are consistent and specific and can assist in the noninvasive diagnosis of abscesses. Responses to combined treatment could be monitored by showing the changes in metabolite patterns in serial spectroscopic studies.

Adolescent↗