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Biomedical subjects

P Dasgupta

Publications and source records attributed to P Dasgupta.

At least 73 records · Page 4Linked to original sources
PubMed1998

Electromotive drug administration of lidocaine to anesthetize the bladder before intravesical capsaicin.

PURPOSE: The discomfort caused by intravesical capsaicin during instillation may restrict its use in some patients. We studied the effectiveness of using electromotive drug administration (EMDA) of lidocaine to anesthetize the bladder before capsaicin. MATERIALS AND METHODS: EMDA of lidocaine and epinephrine was performed in 8 patients with detrusor hyperreflexia using catheters, electrodes and an electrical current generator (20 mA., 15 minutes) followed immediately by intravesical capsaicin (2 mmol./l.) for 30 minutes under urodynamic monitoring. The patients scored suprapubic pain at 5 minutes and at the end of the capsaicin instillations on a scale of 0 to 10. Of the 8 patients 5 had had previous capsaicin treatments and the scores were compared to previous scores when intravesical lidocaine without EMDA had been used as local anesthesia before capsaicin. RESULTS: The pain scores during capsaicin instillations after EMDA of lidocaine were much lower than those during capsaicin instillations after lidocaine alone. EMDA virtually eliminated the hyperreflexic contractions of the bladder occurring during capsaicin instillations, thus reducing the risk of urethral leakage, and prevented autonomic dysreflexia that had previously occurred in 1 patient. CONCLUSIONS: EMDA of lidocaine is an effective means of reducing pain during subsequent intravesical capsaicin, which makes the use of capsaicin in the treatment of detrusor hyperreflexia more acceptable.

Administration, Intravesical↗
PubMed1998

Treating the human bladder with capsaicin: is it safe?

OBJECTIVES: Although human contact with capsaicin has occurred over thousands of years, some uncertainty surrounds its status as a possible carcinogen. This is the first report of bladder biopsies from patients who have been treated with capsaicin over a 5-year period. METHODS: Between 1991 and 1996, 20 patients (9 males, 11 females; mean age 52.5 years, range 40-70 years) with intractable detrusor hyperreflexia have had repeated instillations of intravesical capsaicin (1-2 mmol/l). The number of treatments per patient varied between 1 and 17 (total = 82; average 6/patient). The surveillance programme involved repeated flexible cystoscopy and bladder biopsies before and after capsaicin. Cryostat sections were stained with haematoxylin-eosin and examined by light microscopy. RESULTS: None of the bladder biopsies have shown metaplasia, dysplasia, flat carcinoma in situ, papillary or solid invasive cancer. CONCLUSIONS: No pre-malignant of malignant change has been found in biopsies of patients who had repeated capsaicin instillations for up to 5 years. However, as the morphological effects of chemical carcinogens may not be apparent for 10 years, further surveillance is being continued.

Adult↗
PubMed1997

Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long-term followup.

PURPOSE: We described the long-term outcome of intravesical capsaicin instillations in patients with urinary incontinence and compared its efficacy in 2 similar populations of patients with multiple sclerosis in a dual center study. MATERIALS AND METHODS: During 5 years 79 patients with intractable urinary incontinence have been treated with intravesical capsaicin. The majority of patients had spinal cord disease due to multiple sclerosis but 4 were neurologically normal. Cystometry was performed before and 4 to 6 weeks after intravesical instillation of 1 to 2 mmol./l. of capsaicin in 30% ethanol in saline. Instillations of vehicle (30% ethanol in saline) alone were carried out in 5 patients. RESULTS: In patients with phasic detrusor hyperreflexia complete continence was achieved in 44%, satisfactory improvement occurred in 36% and treatment failed in 20%. Clinical benefit from a single instillation lasted 3 to 6 months and was repeated in some patients with similar improvement. Capsaicin was ineffective in patients with poor bladder compliance and in neurologically normal patients with sensory urgency and detrusor instability. There was no clinical or urodynamic improvement in patients treated with vehicle alone. There have been no long-term complications. CONCLUSIONS: Our study shows that repeated instillations of intravesical capsaicin are effective in treatment of patients with detrusor hyperreflexia due to spinal cord disease and that effectiveness of the treatment persists at least 3 to 5 years.

Administration, Intravesical↗
PubMed1997

The 'Queen Square bladder stimulator': a device for assisting emptying of the neurogenic bladder.

OBJECTIVE: To describe the effectiveness of a vibrating device for emptying the neurogenic bladder in patients with neurological disease. PATIENTS AND METHODS: The study involved 36 patients, comprising 29 with multiple sclerosis (MS), four with multiple system atrophy (MSA), one with radiation myelitis and two with neurological disease of uncertain aetiology. Most patients with MS (27) were able to walk unaided or with aids. Three of the 36 patients had loss of suprapubic sensation (two MS, one with uncertain diagnosis). All patients had free flow rates and ultrasonographic post-void residual volumes (PVRs) measured before and after voiding while using a vibrating device (frequency 60 Hz) applied to the suprapubic region. They also completed questionnaires about their urinary symptoms before and after the continued use of this device. The mean follow-up was 11.5 months (range 8-14). RESULTS: The device improved the symptoms in 25 of 36 patients (70%) and reduced the PVR from a mean (standard deviation) of 175 (78) mL to 68 (32) mL. It was not useful in patients with PVRs of > 400 mL, Kurtzke pyramidal function scores of > 3, and in those with suprapubic numbness. There were no complications and most patients complied well. CONCLUSIONS: Suprapubic vibration is an effective means of emptying the neurogenic bladder in patients who are not severely disabled and who have detrusor hyper-reflexia. It probably acts through a tonic vibration reflex which is under supraspinal influence. This device may be a useful alternative to clean intermittent self-catheterization.

Follow-Up Studies↗
PubMed1993

Alternative splicing of the chicken c-myb exon 9A.

The c-myb gene products are thought to be regulators of cellular replication and of differentiation and heterogeneity may underlie their multiple functions. To investigate the possible existence of heterogeneity we have examined the chicken c-myb mRNAs by Northern blot analysis and polymerase chain reaction amplification of cDNAs (RT-PCR). Northern blot analysis with the c-myb cDNA clone pSG3, which contains the entire open reading frame (ORF) plus 500 base pairs of 3' untranslated sequences (Gerondakis & Bishop, 1986), and genomic probes revealed c-myb RNA species of 4.3 kb in addition to the major 4.0 kb species. The 4.3 kb c-myb RNA contained the alternatively spliced exon 9A which is highly conserved and has also been detected in a minor 4.3 kb alternatively spliced c-myb mRNA in murine and human cells. Sequencing of the avian exon 9A revealed 360 bp exon homologous to that found in murine and human mRNAs, which contains three highly conserved sequence regions shared by all three species. RT-PCR demonstrated usage of exon 9A in five hematopoietic tissues and revealed an additional splicing variant which used the 3' portion of exon 9A. Northern blot analysis using splice site-specific oligonucleotide probes spanning the two splice junctions between exon 9 and 9A revealed four additional c-myb RNAs of 4.4 kb, 2.2 kb, 2.0 kb and 1.4 kb.

Alternative Splicing↗
PubMed1992

The cellular proto-oncogene product Myb acts as transcriptional activator of the long terminal repeat of human T-lymphotropic virus type I.

The proto-oncogene c-myb encodes a nuclear transcription factor that binds to DNA in a sequence-specific manner and activates transcription of several viral and cellular genes. Expression of the c-myb gene is induced in mitogen- and/or antigen-stimulated T lymphocytes, which are also the preferential target cells of human T-lymphotropic virus type I (HTLV-I) in vivo and in vitro. We report here that Myb binds to the HTLV-I long terminal repeat (LTR) in four different regions in a sequence-specific manner. Electrophoretic mobility shift assay using labeled LTR fragments as well as labeled double-stranded oligonucleotides show that there are two high-affinity and two low-affinity Myb-binding sites present in the HTLV-I LTR. DNase I footprinting analysis and oligonucleotide competition experiments indicate that this binding is sequence specific. Cotransfection experiments in HeLa cells, using a Myb expression vector and chloramphenicol acetyltransferase reporter gene linked to the HTLV-I LTR, show that Myb activates HTLV-I LTR-mediated transcription by a factor of four-to sixfold. Thus, in HTLV-I-infected T cells, Myb protein binding to the HTLV-I LTR may constitute one of the signal that regulate HTLV-I transcription in vivo.

Base Sequence↗
PubMed1992

Regulation of HIV-1 gene expression by cellular transcription factors.

The human CD4+ T lymphocytes in the peripheral blood represent a major target for HIV-1 infection in vivo. In the quiescent state T lymphocytes are nonpermissive for the propagation of HIV-1. Antigenic or mitogenic stimulation of T lymphocytes triggers a cascade of biochemical events that lead to cellular proliferation and activation of transcription and replication of HIV-1. Transcription of HIV-1 provirus in infected T cells is regulated by the interaction of both viral proteins and cellular transcription factors with the viral long terminal repeat (LTR) sequences. HIV-1 LTR has been shown to contain recognition sequences for many cellular transcription factors. These include both positive and negative regulatory factors. Interplay of cellular proteins involve both the upstream and downstream regions of the viral LTR. Our full understanding of the transcriptional regulation of HIV-1 provirus will require isolation and characterization of each of these cellular factors which bind to the HIV-1 LTR. Mutational analyses of HIV-1 LTR indicate that not all these various cellular factors are absolutely essential for the regulation of LTR-mediated viral gene expression, but their presence or absence may determine the course of HIV-1 replication in the infected cells. A balance between the inhibitory host transcription factors and the stimulatory cellular and/or viral protein factors possibly determine the final consequence of HIV-1 replication and pathogenesis.

Gene Expression Regulation, Viral↗
PubMed1992

Mutational analysis of Max: role of basic, helix-loop-helix/leucine zipper domains in DNA binding, dimerization and regulation of Myc-mediated transcriptional activation.

The Max protein forms a heterodimeric complex with the Myc family of proteins and binds to DNA in a sequence-specific manner. We investigated the role of the helix-loop-helix (HLH), leucine zipper (LZ) and basic domains of Max in protein complex formation, DNA-binding activity and transcriptional regulation. We mutagenized the basic, HLH and LZ domains of Max and studied the ability of the normal and mutant proteins to bind to DNA as both homo- and heterodimers and their ability to heterodimerize with Myc. Helix-1 and helix-2 regions of Max were found to be critical for homodimer formation and subsequent DNA binding, while the LZ was essential for heterodimer formation. In transient transfection assays the Myc protein functioned as a transcriptional activator while Max protein repressed the trans-activation observed with Myc.

Base Sequence↗
PubMed1990

Ranolazine (RS-43285): a preliminary study of a new anti-anginal agent with selective effect on ischaemic myocardium.

Ranolazine (RS-43285) has been shown to possess significant anti-ischaemic properties in a canine model of reversible myocardial ischaemia. The clinical efficacy of this new agent was assessed by a single blind, placebo controlled study of 14 patients with chronic stable angina. A 2 week placebo phase was followed by therapy with 30 mg and 60 mg of ranolazine tid for 2 weeks each. Graded, symptom limited treadmill exercise tests were performed at the end of each phase, 1.5 h (AM) and 7 h (PM) after the morning dose. An additional exercise test 1.5 h after the first dose of 30 mg was included to assess the acute dose response. In the AM study, the mean exercise time increased from 6.9 min (placebo) to 7.8 min after the first dose of 30 mg and to 8.2 min and 8.5 min respectively at the end of 30 mg and 60 mg phases. In the PM study, exercise time improved from 6.5 min (placebo) to 8.2 min and 7.8 min respectively at the end of 30 mg and 60 mg phases. The time to onset of angina showed a similar improvement. No significant changes were observed in the resting and peak exercise heart rates and blood pressure. This preliminary study suggests that ranolazine may significantly prolong exercise time in patients with stable coronary artery disease without altering heart rates and blood pressure.

Acetanilides↗
PubMed1990

Ambulatory intra-arterial blood pressure in normal subjects.

It has been suggested that ambulatory blood pressure monitoring is superior to casual cuff methods in predicting cardiovascular events, but lack of reference data from a normal population seriously limits this method's clinical applicability. We therefore performed 24-hour intra-arterial ambulatory blood pressure (BP) monitoring in 50 normal volunteers (cuff BP less than 140/90 mm Hg) whose ages ranged from 18 to 74 years. There were 30 men and 20 women in the study, but there was no significant difference between the sexes with respect to age, cuff BP, or body mass index. A diurnal variation in BP was observed, qualitatively similar to that seen in hypertensive individuals, including a prewaking BP rise. Mean daytime intra-arterial pressures differed little between the sexes (124/74 mm Hg for women and 127/76 mm Hg for men, p = NS), but was lower at night in women than in men (96/52 versus 102/59 mm Hg, respectively; p less than 0.02 for diastolic pressure). Based on this group of subjects, we defined the upper limit of normal daytime BP in both men and women as 150/90 mm Hg and the upper limit of mean nighttime BP as 130/80 mm Hg for men and 115/65 mm Hg for women. The lower nighttime pressures in women compared with their male counterparts with similar daytime pressures may explain why women appear to tolerate similar levels of BP better than men.

Adolescent↗
PubMed1990

Myb protein binds to human immunodeficiency virus 1 long terminal repeat (LTR) sequences and transactivates LTR-mediated transcription.

The protooncogene c-myb encodes a nuclear transcription factor that binds to DNA in a sequence-specific manner and transactivates transcription of several viral and cellular genes. The expression of c-myb is induced in mitogen-stimulated peripheral blood lymphocytes and is constitutively expressed in several CD4+ T-cell and myeloid cell lines, all of which constitute excellent targets for human immunodeficiency virus (HIV) infection and replication. We looked for the presence of Myb-binding motifs in human retroviral long terminal repeats (LTRs) and tested for Myb binding to HIV-1 LTR sequences by using a highly purified recombinant Myb protein. Our results show that HIV-1 LTR contains one high-affinity Myb-binding site along with two or more low-affinity binding sites. DNase I protection analysis as well as oligonucleotide competition experiments indicate that this binding is sequence specific. Introduction of purified Myb protein directly into HeLa cells harboring HIV-1 LTR chloramphenicol acetyltransferase vectors indicates that Myb protein transactivates HIV-1 LTR-mediated transcription. Thus, Myb protein binding to HIV LTR sequences may constitute one of the signals that regulates HIV-1 transcription.

Base Sequence↗
PubMed1989

Cardiovascular changes in obese subjects on very low calorie diet.

The effect of 330 kcal/day diet on cardiac function, blood pressure and cardiac chambers was studied in 34 obese subjects, using radionuclide ventriculography, intra-arterial ambulatory blood pressure recording and echocardiography. The group included 15 hypertensives and nine with coronary artery disease. After 4 weeks dieting, mean body weight fell from 105.6 +/- 22 kg to 96.1 +/- 19 kg (P less than 0.001), mean blood pressure fell from 157 +/- 23 to 144 +/- 21 mmHg systolic and 90 +/- 15 to 85 +/- 13 mmHg diastolic (P less than 0.001). The resting left ventricular ejection fraction after dieting fell significantly only in the hypertensive group (P less than 0.0005). Left ventricular ejection fraction response to exercise was impaired in all subjects. After weight loss this returned to normal except in the coronary artery disease group. There was a significant reduction in left ventricular internal dimensions, left ventricular fraction shortening and left ventricular mass after weight loss.

Adult↗
PubMed1989

Molecular cloning of the breakpoint region on chromosome 6 in cutaneous malignant melanoma: evidence for deletion in the c-myb locus and translocation of a segment of chromosome 12.

Nonrandom involvement of chromosome 6 in cutaneous malignant melanoma have been noted by several investigators. Recently an alteration in the c-myb locus (6q22-23) has been identified by Southern analysis in the WM983A cell line which was derived from a primary melanoma of the vertical growth phase. In the present study, the nature of this rearrangement in the WM983A cell line has been further characterized by molecular cloning and nucleotide sequence analysis of the break-point region in the c-myb locus. The results of this investigation demonstrate that the rearrangement in the 6q22-23 region results in deletion of the 3'-end of the c-myb locus with the concomitant translocation of a portion of chromosome 12 to chromosome 6.

Base Sequence↗