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Biomedical subjects

J Khan

Publications and source records attributed to J Khan.

At least 19 recordsLinked to original sources

Accuracy of choroidal melanoma diagnosis by general ophthalmologists: a prospective study.

PURPOSE: To estimate the proportion of 'false positives' in patients referred with a diagnosis of suspected choroidal melanoma by general ophthalmologists to an ocular oncology centre. METHODS: A prospective study of patients referred by general ophthalmologists to an ocular oncology centre was undertaken over a 14-week period. The diagnosis was made clinically in patients receiving radiotherapy or phototherapy and was confirmed by histopathology in patients requiring fine needle aspiration biopsy (FNAB) or enucleation. RESULTS: A total of 132 new patients were seen in 10 consecutive ocular oncology clinics between 29 March 2004 and 5 July 2004. The mean age was 62 years (range 28-88 years) and 60 (55%) were female. Among the 83 suspected malignant posterior segment lesions, the suspected diagnosis included choroidal melanoma (73), choroidal metastasis (6), 'choroidal tumour' (3), and 'Solid retinal detachment' (1). Only 50 of the 73 suspected melanomas were confirmed (68.5%; 95% CI, 57-78%), the oncologist's diagnosis in the remaining 23 being choroidal naevus (10), choroidal metastasis (1), circumscribed choroidal haemangioma (2) and others (10). Only one of six patients with suspected metastases had this condition, the remainder having melanoma (1), lymphoma (1), circumscribed choroidal haemangioma (1), and others (2). The 'choroidal tumours' and 'solid detachments' were found to be chorio-retinal disciform scar (1), varix of vortex vein (1), eccentric CNV (1), and subretinal haemorrhage (1) CONCLUSION: Approximately 30% of patients referred to an ocular oncology service with the diagnosis of choroidal melanoma have an incorrect diagnosis.

Adult↗

Acquired weakness in the ICU: critical illness myopathy and polyneuropathy.

Illnesses commonly encountered in the ICU, such as sepsis, have frequently been associated with neuromuscular weakness and may play a role in the development of CIM and CIP, whose incidence in the critically ill is greater than initially reported. Although difficult to diagnose from history and clinical/laboratory findings alone, the use of electromyographic and nerve conduction testing is helpful in establishing these diagnoses. Information regarding prognosis of these disorders is limited, and there are no specific therapies that improve outcome. Acquired neuromuscular weakness in the ICU affects a significant number of patients and may continue to affect their quality of life long after discharge. Although diagnostic techniques are readily available, additional research is necessary to obtain adequate prognostic information and therapeutic options for these patients.

Critical Illness↗

The prevalence and associated features of posterior embryotoxon in the general ophthalmic clinic.

PURPOSE: To estimate the prevalence of posterior embryotoxon (PE) in the general ophthalmic clinic and to identify any features of PE that suggest that it is pathological rather than physiological. METHODS: Over 700 consecutive patients of all ages were examined with the slit lamp during their routine eye clinic appointment. Patients with posterior embryotoxon were invited to return for full ocular examination including keratometry, corneal topography, and gonioscopy. RESULTS: In all, 49 out of 723 patients were found to have PE. This gives a prevalence of 6.8% with an age range of 18 months to 95 years. There was a higher prevalence in the younger age group of 22.5% (age range 18 months to 20 years) compared to 5.9% in the older age range (21-95 years). A total of 29 patients with PE returned for further examination. Six patients had glaucoma (two with Axenfeld's syndrome and one with aniridia), and one had ocular hypertension. In all, 20 patients had bilateral PE on slit-lamp examination, which increased to 24 with gonioscopy. The majority of the PE was seen temporally (97.9%) and limited to a few clock hours. Gonioscopy showed that eight patients with PE had associated inferior pigmentation of schwalbes line. CONCLUSION: This large series found the prevalence of PE the general ophthalmic clinic to be 6.8%. Its presence should prompt careful anterior segment examination, including gonioscopy, to identify any associated abnormalities that may carry a risk of glaucoma. Children should also be assessed for any associated systemic or genetic abnormality.

Abnormalities, Multiple↗

Heteroassociative multiple-target tracking by fringe-adjusted joint transform correlation.

A heteroassociative joint transform correlation (JTC) technique is proposed for recognizing and tracking multiple heteroassociative or dissimilar targets from gray-level image sequences by use of the concept of fringe-adjusted JTC and a multiple-target-detection algorithm. A fringe-adjusted JTC technique is used to ensure quantification of the similarities among several input images while it satisfies the equal-correlation-peak criterion. Tracking is accomplished by retrieval of the target motion information estimated from multiple consecutive image frames. An enhanced version of the fringe-adjusted filter is incorporated into the heteroassociative multiple-target-detection process to optimize the correlation performance. The feasibility of the proposed technique is tested by computer simulation with real infrared image data.

Journal Article↗

Sputum T lymphocytes in asthma, COPD and healthy subjects have the phenotype of activated intraepithelial T cells (CD69+ CD103+).

BACKGROUND: T cells of intraepithelial phenotype have previously been detected in bronchoalveolar lavage (BAL) fluid in a range of lung diseases; these cells express the adhesion molecule alpha(E)beta(7) integrin, CD103, the ligand for epithelial cell E-cadherin. In subjects with asthma CD4+ lymphocytes are the predominant T cell subtype found in bronchial biopsy specimens and in BAL fluid, whereas CD8+ lymphocytes have been shown to predominate in subjects with chronic obstructive pulmonary disease (COPD). The aim of this study was to analyse the expression of CD103, activation markers (CD25 and CD69), and chemokine receptors (CXCR3, CCR5 and CCR3) on CD4+ and CD8+ lymphocytes from sputum and peripheral blood of subjects with asthma, COPD, and healthy controls. METHODS: T cell surface markers were assessed by immunofluorescence labelling and flow cytometry of gated lymphocytes among CD45+ leucocytes in sputum cell suspensions. RESULTS: Sputum lymphocytes expressed higher levels of CD103 and CD69 than blood lymphocytes in all subject groups, with CD103 expressed at higher levels on CD8+ than on CD4+ cells. There were no detectable differences in numbers of CD4+ and CD8+ T cells between subjects with asthma, COPD and controls. The percentage of sputum lymphocytes expressing CXCR3 was lower in subjects with asthma or COPD than in healthy controls; CCR3 was not detectable on sputum or blood lymphocytes. CONCLUSIONS: Sputum T lymphocytes are predominantly of activated intraepithelial phenotype (CD103+ CD69+), and normal numbers of CD4+ and CD8+ T cell populations are found in the sputum of patients with asthma and COPD.

Adult↗

Tuberculosis diagnosis and treatment practices of private physicians in Karachi, Pakistan.

In a densely populated urban area of Karachi, Pakistan, a questionnaire survey was made of the knowledge and practices of 120 private general practitioners about the diagnosis and treatment of tuberculosis (TB). The majority knew that cough, fever and weight loss were the main symptoms of TB, but less than half knew that blood in sputum, poor appetite and chest pain were associated with the disease. Only 58.3% of physicians used sputum microscopy for diagnosing TB and 35.0% used it as a follow-up test. Only 41.7% treated TB patients themselves, the remaining referring their patients to specialists. Around 73.3% of the doctors were aware of the 4 first-line anti-TB drugs. Efforts to improve the knowledge of private practitioners, and strategies to enhance public-private collaboration forTB control in urban areas are urgently required.

Anorexia↗

Metastasis-associated differences in gene expression in a murine model of osteosarcoma.

Despite advances in the management of osteosarcoma (OSA) and other solid tumors, the development of metastasis continues to be the most significant problem and cause of death for cancer patients. To define genetic determinants of pulmonary metastasis, we have applied cDNA microarrays to a recently described murine model of OSA that is characterized by orthotopic tumor growth, a period of minimal residual disease, spontaneous pulmonary metastasis, and cell line variants that differ in metastatic potential. Microarray analysis defined 53 genes (of 3166 unique cDNAs) that were differentially expressed between the primary tumors of the more aggressive (K7M2) and less aggressive (K12) OSA models. By review of the literature, these differentially expressed genes were assigned to six nonmutually exclusive metastasis-associated categories (proliferation and apoptosis, motility and cytoskeleton, invasion, immune surveillance, adherence, and angiogenesis). Functional studies to evaluate K7M2 and K12 for differences in each of these metastasis-associated processes revealed enhanced motility, adherence, and angiogenesis in the more aggressive K7M2 model. For this reason, 10 of the 53 differentially expressed genes that were assigned to the motility and cytoskeleton, adherence, and angiogenesis categories were considered as most likely to define differences in the metastatic behavior of the two models. Ezrin, a gene not described previously in OSA, with functions in motility, invasion, and adherence, was 3-fold overexpressed in K7M2 compared with K12 by microarray. Differential expression for RNA was confirmed by Northern analysis and for protein by immunostaining. Alterations in ezrin protein levels and concomitant cytoskeletal changes in our model confirmed predictions from the arrays. The potential relevance of ezrin in OSA was suggested by its expression in five of five human OSA cell lines. This work represents a rationale approach to the evaluation of microarray data and will be useful to identify genes that may be causally associated with metastasis.

Actins↗

Superselective intra-arterial carboplatin for treatment of intracranial neoplasms: experience in 100 procedures.

BACKGROUND: The results of animal studies suggest that superselective intra-arterial infusion allows the permeation of a high concentration of chemotherapeutic agents within intracranial neoplasms. In the present report, we review our clinical experience with the 100 intra-arterial infusions of carboplatin in intracranial neoplasms not responsive to other treatment modalities. METHODS: Carboplatin was infused in 100 separate sessions (24 patients) as a mean dose of 286+/-60 mg/m2 (range 34-377 mg/m2). RMP-7, a bradykinin analog, was used as an adjunct in 28 sessions (6 patients). The infusions were performed through superselective microcatheterization of the following arteries: internal carotid (n = 39), middle cerebral (n = 61), posterior cerebral (n = 21) and anterior cerebral (n = 10). The frequency of neurological and non-neurological complications, and survival were recorded. In a subset of 10 patients, tumor volume was measured by serial magnetic resonance images to assess therapeutic response to therapy. RESULTS: The mean age of the patients was 44.5 years (range 26-67 years); 13 were men. The tumors were classified as glioblastoma multiforme (n = 12), metastatic tumor (n = 1), high-grade astrocytoma (n = 6), and anaplastic mixed glioma (n = 5). Follow-up was available for 23 patients (mean 22 months, range 2-69 months). Survival beyond 1 year after initiation of intra-arterial carboplatin therapy was documented in 12 of the 23 patients. A total of 13 neurological complications including seizures (n = 7), transient neurological deficits (n = 5), and ischemic stroke (n = 1) were observed in 100 procedures. A lower frequency of complications occurred in men and in patients who received adjunctive RMP-7. Volumetric analysis of serial magnetic resonance images demonstrated tumor mass reduction in 3 out of 10 patients. An increase in tumor mass ranging from 23% to 230% was observed in the other 7 patients over a period ranging from 2.3 to 37.7 months since initiation of carboplatin therapy. CONCLUSIONS: Superselective intra-arterial administration of carboplatin appears feasible and was associated with predominantly transient neurological complications. The addition of RMP-7 to carboplatin therapy appears to be at least as safe as the administration of carboplatin alone and requires further investigation as a means of chemotherapeutic dose intensification.

Adenocarcinoma↗

Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks.

The purpose of this study was to develop a method of classifying cancers to specific diagnostic categories based on their gene expression signatures using artificial neural networks (ANNs). We trained the ANNs using the small, round blue-cell tumors (SRBCTs) as a model. These cancers belong to four distinct diagnostic categories and often present diagnostic dilemmas in clinical practice. The ANNs correctly classified all samples and identified the genes most relevant to the classification. Expression of several of these genes has been reported in SRBCTs, but most have not been associated with these cancers. To test the ability of the trained ANN models to recognize SRBCTs, we analyzed additional blinded samples that were not previously used for the training procedure, and correctly classified them in all cases. This study demonstrates the potential applications of these methods for tumor diagnosis and the identification of candidate targets for therapy.

Burkitt Lymphoma↗

Gene transfer: manipulating and monitoring function in cells and tissues.

1. The ectopic expression of genes has proven to be an extremely valuable tool for biologists. The most widely used systems involve electrically or chemically mediated transfer of genes to immortalized cell lines and, at the other end of the spectrum, transgenic animal models. As would be expected, there are compromises to be made when using either of these broad approaches. Immortalized cell lines have limited "physiological relevance" and transgenic approaches are costly and out of the reach of many laboratories. There is also significant time required for the de novo generation of a transgenic animal. 2. As a viable alternative to these approaches, we describe the use of recombinant adenovirus and Sindbis virus to deliver genes to cells and tissues. 3. We exemplify this approach with studies from our laboratories: (i) an investigation of Ca2+ handling deficits in cardiac myocytes of hypertrophied hearts using infection with recombinant adenovirus encoding either green fluorescent protein (GFP) or the sarcoplasmic/endoplasmic reticulum calcium-ATPase (Serca2a); (ii) a study of the mechanism of macrophage/microglial migration by infection of embryonic phagocytes with a GFP-encoding virus and coculture with brain slices to then track the movement of labelled cells; and (iii) we are also exploiting the natural tropism of the Sindbis virus to label neurons in hippocampal brain slices in culture to resolve high-resolution structure and to map neuronal connectivity. 4. Further development of these approaches should open new avenues of investigation for the study of physiology in a range of cells and tissues.

Adenoviridae↗

Quantitative analysis of injured, necrotic, and apoptotic cells in a new experimental model of intracerebral hemorrhage.

OBJECTIVE: To develop a new survival model of intracerebral hemorrhage (ICH) in rabbits and study the patterns of cellular injury in different regions 24 hrs after introduction of hematoma. Quantitation and characterization of injured cells in regions adjacent and distant to the hematoma have not been performed. DESIGN: Prospective case-control study. SUBJECTS: Ten New Zealand rabbits. INTERVENTION: We introduced ICH in six anesthetized New Zealand rabbits by autologous blood injection under arterial pressure in the deep white matter in the frontal lobe. MEASUREMENTS AND MAIN RESULTS: Hematoxylin and eosin staining was performed in six animals with ICH after 24 hrs to quantify intact, injured, and necrotic cells in regions proximal and distant to the hematoma, and the results were compared with four control animals. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was performed to quantify apoptotic cells in specified regions in five animals with ICH, and the results were compared with four control animals. All cell counts were performed by one investigator who used 100x oil emersion microscopy. The presence of localized hematoma was confirmed in all six animals with blood infusion. Compared with controls, animals with ICH had a significantly higher proportion of swollen cells in both the inner (55.9% +/- 3.0% vs. 26.8% +/- 1.7%; p < .05) and the outer (59.8% +/- 4.6% vs. 27.7% +/- 4.5%; p < .05) rim of the perihematoma region. A small proportion of shrunken dark cells were observed in both the inner (4.0% +/- 1.5%) and the outer (3.6% +/- 1.0%) rim of the perihematoma region. The remaining cells were considered morphologically intact. A large proportion of cells trapped within the matrix of the hematoma were either shrunken dark cells (48.8% +/- 16.4%) or swollen (38.8% +/- 15.1%). In the TUNEL-stained sections, a high burden of apoptotic cells was observed in the matrix of the hematoma (17.5 +/- 6.3 cells per high power field) but not in the perihematoma regions (less than two cells per high power field). CONCLUSIONS: A reproducible model of ICH in rabbits is described. At 24 hrs, the perihematoma region contains relatively large proportions of morphologically intact or reversibly injured (swollen) cells, suggesting the possibility of an extended window for therapeutic intervention.

Analysis of Variance↗

Absence of early proinflammatory cytokine expression in experimental intracerebral hemorrhage.

OBJECTIVE: We sought to analyze the regional concentrations of proinflammatory cytokines in the acute period of intracerebral hemorrhage (ICH) and to test the hypothesis that ICH is associated with the expression of proinflammatory cytokines in the acute period. Although the expression of cytokines and their role in neuronal injury and inflammation is well characterized in cerebral ischemia and head injury, no information exists regarding expression of cytokines in ICH. METHODS: We introduced ICH in eight anesthetized mongrel dogs by autologous blood injection (6 ml) under arterial pressure in the deep white matter adjacent to the left basal ganglia. Samples of arterial blood and cerebrospinal fluid were collected, and tissue extracts were prepared from different regions of the brain for immunoassay of tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 concentrations in animals with and without ICH. RESULTS: The tumor necrosis factor a levels (+/- standard error) in the cerebrospinal fluid 1 hour after ICH did not differ significantly between the ICH group and the control group (7.1 +/- 1.3 pg/ml versus 10.8 +/- 2.3 pg/ml, P = 0.22). Levels in the perihematoma region in the ICH group (96.6 +/- 3.1 pg/ml) were not significantly different from those in the control group (93.4 +/- 6.7 pg/ml, P = 0.7). IL-6 levels (+/- standard error) in the perihematoma region in the ICH group (116.3 +/- 13.3 pg/ml) did not differ significantly from those in corresponding regions in the control group (122.3 +/- 12.8 pg/ml, P = 0.7). IL-1beta levels were below 5 pg/ml in serum, cerebrospinal fluid, and extracts of different brain regions. CONCLUSION: The early pathophysiology of ICH does not involve significant expression of tumor necrosis factor a either in the perihematoma region or other regions of the brain. The observation suggests that the pathophysiology of ICH in the acute period is different from both cerebral ischemia and traumatic brain injury.

Animals↗

Insulin and IGF-1 induce different patterns of gene expression in mouse fibroblast NIH-3T3 cells: identification by cDNA microarray analysis.

The IGF-1 receptor and the related insulin receptor are similar in structure and activate many of the same postreceptor signaling pathways, yet they mediate distinct biological functions. It is still not understood how the specificity of insulin vs. IGF-1 signaling is controlled. In this study, we have used cDNA microarrays to monitor the gene expression patterns that are regulated by insulin and IGF-1. Mouse fibroblast NIH-3T3 cells expressing either the wild-type human IGF receptor or the insulin receptor were stimulated with either IGF-1 or insulin, respectively. Thirty genes, 27 of which were not previously known to be IGF-1 responsive, were up-regulated by IGF-1 but not by insulin. Nine genes, none of which was previously known to be insulin responsive, were up-regulated by insulin but not by IGF-1. The IGF- and insulin-induced regulation of 10 of these genes was confirmed by Northern blot analysis. Interestingly, more than half of the genes up-regulated by IGF-1 are associated with mitogenesis and differentiation, whereas none of the genes specifically up-regulated by insulin are associated with these processes. Our results indicate that under the conditions used in this study, IGF-1 is a more potent activator of the mitogenic pathway than insulin in mouse fibroblast NIH-3T3 cells.

3T3 Cells↗

Endovascular treatment of intracranial aneurysms by using Guglielmi detachable coils in awake patients: safety and feasibility.

OBJECT: Embolization of intracranial aneurysms performed using Guglielmi detachable coils (GDCs) is performed with the patient in a state of general anesthesia at most centers. Such an approach does not allow intraprocedural evaluation of the patient's neurological status and carries additional risks associated with general anesthesia and mechanical ventilation. At the authors' institution, GDC embolization of intracranial aneurysms is performed in awake patients after administration of sedative and analgesic agents (midazolam, fentanyl, morphine, and/or hydromorphone). To determine the feasibility and safety of this approach, the authors have retrospectively reviewed their clinical experience. METHODS: The authors reviewed the medical records of all patients in whom GDC embolization for the treatment of intracranial aneurysms was undertaken between February 1, 1990 and October 31, 1999. Clinical presentation, medical comorbidities, anesthetic agents used, intraprocedural complications, and final procedural outcome were recorded for each patient. Guglielmi detachable coil embolization was attempted in the awake patient in 150 procedures. Among 92 procedures for unruptured aneurysms, 75 (82%) were completed without complications. Four procedures were completed with complications. Of the 92 procedures, 13 were aborted due to patient uncooperativeness (one patient), complications (three patients), morphological characteristics of the aneurysm or surrounding vessels that made embolization technically difficult (eight patients), or vasospasm (one patient). Among 58 procedures for ruptured aneurysms, the procedure was completed without complication in 48 cases (83%). The procedure was completed with complications in five cases and two patients required induction of general anesthesia during the procedure. Five procedures were aborted because morphological characteristics of the aneurysm or surrounding vessels made embolization technically difficult (two patients) or because of aneurysm rupture (two patients) or the appearance of a transient neurological deficit (one patient). CONCLUSIONS: Embolization of intracranial aneurysms performed using GDCs in the awake patient appears to be safe and feasible and allows intraprocedural evaluation of the patient. Potential advantages, including decreased cardiopulmonary morbidity rates, shorter hospital stay, and lower hospital costs, still require confirmation by a direct comparison with other anesthetic procedures.

Adult↗

An observational study of 256 cases of vascular trauma in the north western province of Pakistan.

During the past 10 years Peshawar has dealt with increasing casualties with penetrating trauma inflicted by a wide variety of missiles. The aim of this study was to assess whether delay in arrival and mode of presentation affects the outcome of patients with penetrating vascular trauma. Prospective data were collected on 256 vascular injuries in 248 patients (median age, 29 years; range, 7-60 years) between January 1995 and June 1998. Early presentation (group A, 55 cases, < 12 h) was compared with late presentation (group B, 201 cases, > 12 h). The majority of injuries (93%) were caused by fire-arms. Arterial injuries accounted for 71% of the total, venous injuries accounted for 10% and 19% were mixed. The site of injury was the lower limb (61%), upper limb (32%), abdominal cavity (5%) and neck (2%). Patients presented with absent pulses (56%), haemorrhage (46%), false aneurysms (8%), A-V fistula (5%) and 11% presented with more than one sign. There were significantly more lower limb amputations in group A than group B (23% versus 5%; P < 0.05), with fractures having a positive association with lower limb amputations (odds ratio, 0.32; 95% CI, 0.13-0.94; P < 0.05). Group A had a higher mortality than group B (18% versus 7%; P < 0.05). This study shows that patients with vascular trauma can be managed successfully with clinical assessment alone. Patients with fractures were more likely to suffer eventually from lower limb loss. Due to self-selection, arrival at the hospital less than 12 h after sustaining vascular injury was associated with a higher mortality than those presenting after 12 h.

Adolescent↗