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Biomedical subjects

A Guha

Publications and source records attributed to A Guha.

At least 19 recordsLinked to original sources
PubMed2006

Anaesthesia for endovascular management of cerebral aneurysms.

Subarachnoid haemorrhage due to rupture of cerebral aneurysms is a multisystem disease. Treatment of the condition in the past has relied on craniotomy and clipping of the aneurysm to prevent a recurrent haemorrhage. There is now emerging evidence to suggest that endovascular treatment of cerebral aneurysms may reduce the morbidity associated with open surgery. The anaesthetic management of interventional neuroradiology also creates new challenges due to the novel approach to treatment. Anaesthetists need to be familiar with this procedure and the management of potential complications. This review provides an overview such considerations.

Anesthesia↗
PubMed2006

A randomised, crossover study of the Dorges, McCoy and Macintosh laryngoscope blades in a simulated difficult intubation scenario.

The use of alternative adult laryngoscope blades in an unexpected difficult intubation was evaluated with a human patient simulator manikin. Twenty anaesthetists of varying experience attempted to intubate the trachea of a high fidelity simulator in both its normal and difficult intubation settings using Macintosh, Dorges and McCoy laryngoscopes in a randomised order. The time taken to intubate, Cormack and Lehane scores, percentage of glottic opening visible, failure rate, number of attempts and subjective ease of use were recorded. The Dorges and McCoy blades did not perform any better than the standard Macintosh blade in either the easy or difficult tracheal intubation settings. Guidelines recommending the use of an alternative blade in an unexpected difficult intubation scenario have limited supporting evidence. This study does not support this recommendation.

Cross-Over Studies↗
PubMed2004

Optimal concentration of epidural fentanyl in bupivacaine 0.1% after thoracotomy.

BACKGROUND: The aim of this prospective, double-blind, randomized controlled trial was to investigate the analgesic and adverse effects of three commonly used concentrations of thoracic epidural fentanyl with bupivacaine in patients undergoing thoracotomy for lung resection. METHODS: We studied 99 patients who were randomized to receive fentanyl 2 microg ml(-1) (group 2), fentanyl 5 microg ml(-1) (group 5) and fentanyl 10 microg ml(-1) (group 10) in bupivacaine 0.1% via a thoracic epidural. Postoperatively, pain on coughing was assessed using a visual analogue scale (VAS) and an observer verbal rating score (OVRS) at 2, 8, 16 and 24 h. At the same times, sedation, pruritus and nausea were assessed. RESULTS: Of 29, 28 and 32 patients who completed the study in groups 2, 5 and 10 respectively, there was no significant difference in baseline characteristics between the three groups. The number of patients with episodes of unsatisfactory pain, i.e. VAS scores >30 mm and OVRS >1, at each of the four assessments postoperatively was significantly (P<0.01) higher in group 2 than in groups 5 and 10. In group 10, 16 patients had sedation scores >1 compared with 10 each in groups 2 and 5. In addition, 19 patients in group 10 experienced pruritus compared with 12 each, in groups 2 and 5. These differences were not significant. Nausea was not significantly different between the three groups. CONCLUSION: We conclude that thoracic epidural fentanyl 5 microg ml(-1) with bupivacaine 0.1% provides the optimum balance between pain relief and side effects following thoracotomy.

Aged↗
PubMed2004

Conservative management of vestibular schwannomas - second review of a prospective longitudinal study.

Vestibular schwannomas have been traditionally managed with microsurgical removal and in recent years, stereotactic radiotherapy. However, there is a group of patients in whom a conservative management approach might represent a desirable alternative. The aim of this study was to determine the natural history and outcome following the conservative management of 72 patients with unilateral vestibular schwannomas. This is a prospective cohort review of a previously published group of patients [Clin. Otolaryngol. (2000) 25, 28-39] with unilateral vestibular schwannoma that were initially analysed at our institution in 1998 [Walsh R.M., Bath A.P., Bance M.L. et al., Clin. Otolaryngol. (2000) 25, 28]. The mean duration of follow-up was 80 months (range 52-242 months). All the patients in the study underwent serial magnetic resonance imaging (MRI) for assessment of tumour growth. Patients were deemed to have failed conservative management if there was evidence of rapid radiological tumour growth and/or increasing signs and symptoms, which necessitated active intervention. The mean tumour growth rate for the entire group at the second review was 1 mm/year (range -0.84-9.65 mm/year). The mean growth rate for cerebellopontine angle tumours (1.3 mm/year) was significantly greater than that of internal auditory canal (IAC) tumours (0 mm/year) (P = 0.005). The majority of tumours (87.14%) grew <2 mm/year. There was significant tumour growth seen in 38.9%, no or insignificant growth in 41.7%, and negative growth in 19.4%. Twenty-three patients (32%) failed conservative management at the second review. There was no difference in the outcome of these failed patients in comparison with patients who underwent primary treatment without a period of conservative management. The mean growth rate of tumours in patients that failed conservative management (3.1 mm/year) was significantly greater than that in patients who did not fail (0.2 mm/year) (P < 0.001). No factors predictive of tumour growth or failure of conservative management were identified. Hearing deterioration with pure tone averages (0.5, 1, 2, 3 kHz) and speech discrimination scores occurred irrespective of tumour growth. This prospective study further emphasizes the role of conservative management in selected cases of vestibular schwannomas. Tumours in this study confined to the IAC typically demonstrated minimal or no growth on serial MRI scanning. Regular follow-up with interval scanning is mandatory in all patients.

Adult↗
PubMed2004

Management of traumatic brain injury: some current evidence and applications.

Traumatic brain injury remains a worldwide problem. Newer modalities in the management of such injuries include both drugs and therapeutic strategies. Continuing research in animal models has provided a better understanding of the pathophysiological processes that follow head injury, and this in turn has enabled workers to work on improved treatment targets. Although there are exciting and novel approaches emerging, there is no substitute for meticulous initial resuscitation. Additionally, some of the more well known management options are now better understood. These concepts are discussed in the article.

Absorptiometry, Photon↗
PubMed2003

Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1.

BACKGROUND: Fifteen to 20% of children with neurofibromatosis type 1 (NF1) develop low-grade astrocytomas. Although brain tumors are less common in teenagers and adults with NF1, recent studies have suggested that patients with NF1 are at a significantly increased risk of developing astrocytomas. OBJECTIVE: S: To investigate the genetic basis for astrocytoma development in patients with NF1 beyond the first decade of life. METHODS: The authors performed molecular genetic analyses of 10 NF1-associated astrocytomas representing all World Health Organization (WHO) malignancy grades using fluorescence in situ hybridization, loss of heterozygosity, immunohistochemistry, and direct sequencing. RESULTS: Later-onset NF1-associated astrocytomas, unlike histologically identical sporadic astrocytomas, exhibit NF1 inactivation, supporting a direct association with NF1 rather than a chance occurrence. Furthermore, some of these astrocytomas have homozygous NF1 deletion. In addition, genetic changes observed in high-grade sporadic astrocytomas, including TP53 mutation and CDKN2A/p16 deletion, are also seen in NF1-associated high-grade astrocytomas. CONCLUSIONS: Neurofibromatosis type 1-associated astrocytomas occurring in patients older than 10 years exhibit genetic changes observed in sporadic high-grade astrocytomas. Patients with neurofibromatosis type 1 and germline NF1 deletions may be at risk for developing late-onset astrocytomas.

Adolescent↗
PubMed2003

Shibire mutations reveal distinct dynamin-independent and -dependent endocytic pathways in primary cultures of Drosophila hemocytes.

We have developed a primary cell culture system derived from embryonic and larval stages of Drosophila. This allows for high-resolution imaging and genetic analyses of endocytic processes. Here, we have investigated endocytic pathways of three types of molecules: an endogenous receptor that binds anionic ligands (ALs), glycosylphosphatidylinositol (GPI)-anchored protein (GPI-AP), and markers of the fluid phase in primary hemocytes. We find that the endogenous AL-binding receptor (ALBR) is internalized into Rab5-positive endosomes, whereas the major portion of the fluid phase is taken up into Rab5-negative endosomes; GPI-APs are endocytosed into both classes of endosomes. ALBR and fluid-phase-containing early endosomes subsequently fuse to yield a population of Rab7-positive late endosomes. In primary culture, the endocytic phenotype of ALBR internalization in cells carrying mutations in Drosophila Dynamin (dDyn) at the shibire locus (shits) parallels the temperature-sensitive behavior of shits animals. At the restrictive temperature in shits cells, receptor-bound ALs remain completely surface accessible, localized to clathrin and alpha-adaptin-positive structures. On lowering the temperature, ALs are rapidly sequestered, suggesting a reversible block at a late step in dDyn-dependent endocytosis. By contrast, GPI-AP and fluid-phase endocytosis are quantitatively unaffected at the restrictive temperature in shits hemocytes, demonstrating a constitutive dDyn and Rab5-independent endocytic pathway in Drosophila.

Animals↗
PubMed2002

Gliomas presenting after age 10 in individuals with neurofibromatosis type 1 (NF1).

Children with neurofibromatosis 1 (NF1) often develop low-grade gliomas, but brain tumors are infrequently encountered in adults with NF1. The authors present evidence from two clinical series, one including patients known to have NF1 and another focusing on adults with new onset brain tumors, that suggests an association between NF1 and symptomatic gliomas in older individuals. They also summarize the clinical data on 17 adolescents or adults with NF1 and symptomatic gliomas. The findings suggest that individuals with NF1 are at increased risk of developing gliomas throughout their lives.

Adolescent↗
PubMed2002

Effect of outer-membrane permeabilizers on the activity of antibiotics and plant extracts against Pseudomonas aeruginosa.

Several known outer membrane permeabilizers increased susceptibility of a highly resistant pathogenic strain Pseudomonas aeruginosa to different antibiotics and plant extracts. Of all the chemicals tested, EDTA, sodium citrate and sodium hexametaphosphate (HMP) were found to be potent permeabilizers as shown by enhanced lysis of the bacteria in the presence of lysozyme. In the presence of EDTA and sodium citrate susceptibility of the strain to gentamicin and rifampicin increased markedly. The strain was resistant to vancomycin but became susceptible when grown in the presence of increasing amounts of EDTA and sodium citrate. Similar results were obtained for erythromycin when treated with sodium citrate. EDTA was found to be most potent permeabilizer in enhancing the activity of the plant extracts. Though HMP was an effective permeabilizer it had a weak or no effect on the activity of the antibiotics and plant extracts.

Anti-Bacterial Agents↗
PubMed2002

Gastric emptying in post-thoracotomy patients receiving a thoracic fentanyl-bupivacaine epidural infusion.

BACKGROUND AND OBJECTIVE: The effect of anaesthesia and surgery on gastric emptying is not constant, and this has not been previously studied in patients undergoing thoracotomy for lung resection with a bupivacaine-fentanyl epidural infusion for analgesia. There are important implications in this group of patients with regards to the recommencement of important oral medication as well as the risks of aspiration of gastric contents. The study examined gastric emptying in these patients until the second postoperative day. METHODS: In a prospective repeated measures study, the effect of fentanyl-bupivacaine epidural analgesia at the mid-thoracic level on gastric emptying was assessed in 11 patients undergoing thoracotomy for lung resection. Gastric emptying was measured using a paracetamol absorption technique. Patients acted as their preoperative controls and were assessed 4 h postoperatively and on the second postoperative day. RESULTS: The mean (SEM) maximum plasma paracetamol concentration was 204.6 (20.4) micromol L(-1) before operation, 61 (9.5) micromol L(-1) 4 h postoperatively and 114.3 (22.6) micromol L(-1) on the second postoperative day. Mean (SEM) paracetamol absorption at 120 min was 15,638 (1441) micromol min L(-1) preoperatively, 5731 (821) micromol min L(-1) 4 h postoperatively and 9325 (1759) micromol min L(-1) on the second postoperative day. Postoperative values were significantly (P < 0.005) less than the preoperative values. CONCLUSIONS: After thoracotomy, gastric emptying was delayed until at least the second postoperative day in patients receiving mid-thoracic fentanyl-bupivacaine epidural analgesia.

Aged↗
PubMed2001

Heterozygosity for the neurofibromatosis 1 (NF1) tumor suppressor results in abnormalities in cell attachment, spreading and motility in astrocytes.

Individuals with the neurofibromatosis 1 (NF1) tumor predisposition syndrome develop low-grade pilocytic astrocytomas at an increased frequency. Previously, we demonstrated that astrocytes from mice heterozygous for a targeted mutation in the Nf1 gene (Nf1+/- astrocytes) exhibit a cell autonomous growth advantage associated with increased RAS pathway activation. In this report, we extend our initial characterization of the effect of reduced Nf1 gene expression on astrocyte function by demonstrating that Nf1+/- astrocytes exhibit decreased cell attachment, actin cytoskeletal abnormalities during the initial phases of cell spreading, and increased cell motility. Whereas these cytoskeletal abnormalities were also observed in Nf1-/- astrocytes, astrocytes expressing a constitutively active RAS molecule showed increased cell motility and abnormal actin cytoskeleton organization during cell spreading, but exhibited normal cell attachment. Based on ongoing gene expression profiling experiments on human astrocytoma tumors, we demonstrate increased expression of two proteins implicated in cell attachment, spreading and motility (GAP43 and T-cadherin) in Nf1+/- and Nf1-/- astrocytes. These results support the emerging notion that tumor suppressor gene heterozygosity results in abnormalities in cell function that may contribute to the pathogenesis of non-tumor phenotypes in NF1.

Animals↗
PubMed2001

Isotype-specific Ras.GTP-levels predict the efficacy of farnesyl transferase inhibitors against human astrocytomas regardless of Ras mutational status.

Previous studies have demonstrated that astrocytomas express elevated levels of activated Ras.GTP despite the absence of activating Ras mutations. Farnesyl transferase inhibitors (FTIs) exert their antitumor effect in part through inhibition of Ras-mediated signaling. SCH66336 is a potent FTI presently undergoing clinical trials in patients with solid tumors. We evaluated the efficacy of SCH66336 against a panel of eight human astrocytoma cell lines and three human astrocytoma explant xenograft models in NOD-SCID mice. SCH66336 demonstrated variable antiproliferative effects against the cell lines, with IC(50) ranging from 0.6 microM to 32.3 microM. Two of the three human glioblastoma multiforme (GBM) xenografts demonstrated substantial growth inhibition in response to SCH66336, with up to 69% growth inhibition after 21 days of treatment. Drug efficacy could be accurately predicted using a combination of the H-, K-, and N-isotype-specific Ras.GTP levels. These data indicate that the absence of Ras mutations does not preclude chemotherapeutic efficacy by FTIs, that Ras is likely a major target of FTIs regardless of Ras mutational status, and that isotype-specific Ras.GTP levels are a promising marker of drug efficacy.

Alkyl and Aryl Transferases↗
PubMed2001

Astrocyte-specific expression of activated p21-ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas.

Activation of the p21-ras signaling pathway from aberrantly expressed receptors promotes the growth of malignant human astrocytomas. We developed a transgenic mouse astrocytoma model using the glial fibrillary acidic protein (GFAP) promoter to express oncogenic V(12)Ha-ras, specifically in astrocytes. The development of GFAP-immunoreactive astrocytomas was directly proportional to the level of V(12)Ha-ras transgene expression. Chimeras expressing high levels of V(12)Ha-ras in astrocytes died from multifocal malignant astrocytomas within 2 weeks, whereas those with moderate levels went to germ-line transmission. Ninety-five percent of these mice died from solitary or multifocal low- and high-grade astrocytomas within 2-6 months. These transgenic astrocytomas are pathologically similar to human astrocytomas, with a high mitotic index, nuclear pleomorphism, infiltration, necrosis, and increased vascularity. Derivative astrocytoma cells are tumorigenic upon inoculation in another host. The transgenic astrocytomas exhibit additional molecular alterations associated with human astrocytomas, including a decreased or absent expression of p16, p19, and PTEN as well as overexpression of EGFR, MDM2, and CDK4. Cytogenetic analysis revealed consistent clonal aneuploidies of chromosomal regions syntenic with comparable loci altered in human astrocytomas. Therefore, this transgenic mouse astrocytoma model recapitulates many of the molecular histopathological and growth characteristics of human malignant astrocytomas in a reproducible, germ-line-transmitted, and high-penetrance manner.

Animals↗
PubMed2001

Mouse astrocytoma models: embryonic stem cell mediated transgenesis.

The development of rational and targeted therapies for human astrocytomas is heavily dependent on our knowledge of its molecular pathogenesis, combined with the generation of appropriate pre-clinical mouse models. The ability to manipulate the mouse genome. which is nearing completion and is highly homologous to its human counterpart, has significantly accelerated our ability to create transgenic mouse models that replicate the pathological and molecular characteristics found in human astrocytomas. These models should serve to further our knowledge of the molecular pathogenesis of human astrocytomas, and serve as useful reagents to test conventional and novel therapeutics.

Animals↗
PubMed2001

The Montgomery T-tube: anaesthetic problems and solutions.

The Montgomery T-tube is a device used as a combined tracheal stent and an airway after laryngotracheal surgery. The device is used mostly in specialist centres for head and neck surgery, and therefore, many anaesthetists may be unfamiliar with its use. The Montgomery T-tube presents the anaesthetist with challenges both during its surgical insertion when acute loss of the airway might occur and also during induction of anaesthesia in patients who have such a tube in situ. Anaesthetists who are unfamiliar with the tube may have to resort to ingenious ways of coping with the problems of a shared airway with a T-tube, which does not have a suitable adaptor for a standard catheter mount, as well as controlling and maintaining ventilation through the device. Safe management of such patients requires careful planning. We describe the anaesthetic management of two cases to illustrate the problems associated with Montgomery tubes.

Adult↗
PubMed2001

Expression and hypoxic regulation of angiopoietins in human astrocytomas.

Vascular endothelial growth factor (VEGF) is a major inducer of tumor angiogenesis and edema in human astrocytomas by its interaction with cognate endothelial-specific receptors (VEGFR1/R2). Tie1 and Tie2/Tek are more recently identified endothelial-specific receptors, with angiopoietins being ligands for the latter. These angiogenic factors and receptors are crucial for the maturation of the vascular system, but their role in tumor angiogenesis, particularly in astrocytomas, is unknown. In this study, we demonstrate that the angiopoietin family member Ang1 is expressed by some of the astrocytoma cell lines. In contrast to VEGF, Ang1 is down regulated by hypoxia. Ang2 was not overexpressed. Expression profiles of low-grade astrocytoma specimens were similar to those of normal brain, with low levels of Ang1, Ang2, and VEGF expression. Glioblastoma multiforme expressed higher levels of Angl, but not to the same degree as pseudopalisading astrocytoma cells around necrotic and hypoxic zones expressed VEGF, as shown in previous studies. Ang2 expression in the highly proliferative tumor vascular endothelium was also increased, as was phosphorylated Tie2/Tek. The expression profile of these angiogenic factors and their endothelial cell receptors in human glioblastomas multiforme was similar to that in a transgenic mouse model of glioblastoma multiforme. These data suggest that both VEGF and angiopoietins are involved in regulating tumor angiogenesis in human astrocytomas.

Angiopoietin-1↗