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Biomedical subjects

A Sehgal

Publications and source records attributed to A Sehgal.

At least 19 recordsLinked to original sources

Cervical cancer screening in India: strategies revisited.

With the change in the life styles and demographic profiles of developing countries, noncommunicable diseases are emerging to be important health problems that demand appropriate control program before they assume epidemic proportion. One of these is the problem of cancer. In India, cervical cancer is a significant problem in terms of incidence, mortality and morbidity. Cervical cancer is a disease that can be prevented through both primary prevention and early detection using screening techniques. Several screening modalities are now available for early detection of cervical cancer and its precursor lesions. They all differ with regard to their test characteristics, feasibility and economic considerations. This communication reviews different aspects of these screening modalities and provides different options considering mass application.

Developing Countries↗

Stable oxide nanoparticle clusters obtained by complexation.

We report on the electrostatic complexation between polyelectrolyte-neutral copolymers and oppositely charged 6-nm crystalline nanoparticles. For two different dispersions of oxide nanoparticles, the electrostatic complexation gives rise to the formation of stable nanoparticle clusters in the range 20-100 nm. It is found that inside the clusters, the particles are "pasted" together by the polyelectrolyte blocks adsorbed on their surface. Cryo-transmission electronic microscopy allows visualization of the clusters and determination of the probability distribution functions in size and in aggregation number. The comparison between light scattering and cryo-microscopy results suggests the existence of a polymer brush around the clusters.

Journal Article↗

Test characteristics of various screening modalities for cervical cancer: a feasibility study to develop an alternative strategy for resource-limited settings.

OBJECTIVE: To determine test characteristics - sensitivity, specificity, positive and negative predictive values - of different screening modalities to detect cervical precancerous and cancerous lesions in order to devise an effective alternative strategy for cervical cancer screening in resource-poor settings. METHODS: A total of 472 women presenting with nonspecific gynecologic symptoms were screened by cytology, visual inspection with acetic acid application (VIA), VIA with magnification (VIAM) and human papillomavirus (HPV)-DNA testing. Colposcopic examination was performed in all and on-site biopsy was taken if any grade I and above lesion was detected on colposcopy (230). On histopathological examination, 105 showed cervical intraepithelial neoplasia II and above lesions. Sensitivity, specificity and predictive values for each test were calculated taking colposcopy and or directed biopsy as the gold standard. Comparisons were made with cytology in order to assess the feasibility of alternative strategies in resource-poor settings. RESULTS: VIA was less sensitive (86.7% versus 91.4%) but more specific (90.7% versus 86.6%) than cytology at low grade squamous intraepithelial lesion (LSIL) threshold but the difference was not statistically significant (P > 0.01). HPV testing improved the sensitivity over cytology (97.1% versus 91.4%) but there was a nonsignificant loss of specificity (84.2% versus 86.6%). Results of VIAM were more or less similar to VIA. CONCLUSION: VIA can be used as a mass screening tool for cervical cancer in resource-poor settings.

Adult↗

Precipitation-redispersion of cerium oxide nanoparticles with poly(acrylic acid): toward stable dispersions.

We exploit a precipitation-redispersion mechanism for complexation of short chain polyelectrolytes with cerium oxide nanoparticles to extend their stability ranges. As synthesized, cerium oxide sols at pH 1.4 consist of monodisperse cationic nanocrystalline particles having a hydrodynamic diameter of 10 nm and a molecular weight of 400 000 g mol(-1). We show that short chain uncharged poly(acrylic acid) at low pH when added to a cerium oxide sols leads to macroscopic precipitation. As the pH is increased, the solution spontaneously redisperses into a clear solution of single particles with an anionic poly(acrylic acid) corona. The structure and dynamics of cerium oxide nanosols and their hybrid polymer-inorganic complexes in solution are investigated by static and dynamic light scattering, X-ray scattering, and chemical analysis. Quantitative analysis of the redispersed sol gives rise to an estimate of 40-50 polymer chains per particle for stable suspension. This amount represents 20% of the mass of the polymer-nanoparticle complexes. This complexation adds utility to the otherwise unstable cerium oxide dispersions by extending the range of stability of the sols in terms of pH, ionic strength, and concentration.

Journal Article↗

Waiting times for radiotherapy: variation over time and between cancer networks in southeast England.

The aim of this study was to investigate variations in the length of time that patients with cancer wait from diagnosis to treatment with radiotherapy. A total of 57,426 men and 71,018 women diagnosed with cancer between 1992 and 2001 and receiving radiotherapy within 6 months of diagnosis were identified from the Thames Cancer Registry database. In total, 12 sites were identified for which a substantial number or proportion of patients received radiotherapy: head and neck, oesophagus, colon, rectum, lung, nonmelanoma skin cancer, breast, uterus, prostate, bladder, brain and non-Hodgkin's lymphoma. Median waiting times from diagnosis to radiotherapy were calculated, together with the proportion of patients who received radiotherapy within 60 days of diagnosis, and analysed by year of diagnosis, cancer site, deprivation quintile, age at diagnosis, sex and cancer network of either residence or treatment. Logistic regression was used to adjust the proportion receiving treatment within 60 days for the effects of the other factors. There were significant differences in the proportions receiving radiotherapy within 60 days between different networks and different cancer sites, which remained after adjustment. Median waiting times varied from 42 to 65 days across networks of residence, with the adjusted proportion treated within 60 days ranging from 44 to 71%. There was no difference between male and female patients after adjustment for the other factors, particularly site. There was a highly significant trend over time: the median wait increased from 45 days in 1992 to 76 days in 2001, while the adjusted proportion being treated within 60 days declined by almost a half, from 64 to 35%, over the same period.

Adult↗

Comparison of the analgesic efficacy and plasma concentrations of high-dose intra-articular and intramuscular morphine for knee arthroscopy.

BACKGROUND AND OBJECTIVE: It is important to provide good postoperative analgesia after discharge from day case surgery. The usefulness of intra-articular morphine for analgesia after day case knee arthroscopy remains controversial. A large dose of morphine intra-articularly may provide a good long-lasting analgesia, but its efficacy and pharmacokinetics are not known and may be no better than intramuscular morphine. We compared the effect of 10 mg intra-articular and intramuscular morphine for 24 h post-injection in a randomized double-blind study. METHODS: Forty adults undergoing knee arthroscopy were recruited and received either 10mg morphine intra-articularly or intramuscularly. Our primary outcome was overall visual analogue assessment of pain (0-100 mm scale where 0 is no pain and 100 is worst possible pain) between 4 h (on discharge) and 24 h (post-operatively). Plasma morphine concentrations were measured at 15 min, and 1, 2, 4 and 24 h. The use of additional analgesia was noted. RESULTS: The assessment of pain experienced between discharge (4 h) and 24 h was significantly better in the intra-articular (n = 20; mean+/-SD: 18+/-19) than the intramuscular (n = 19; mean+/-SD: 34+/-20) group (P = 0.027). The number of patients consuming any additional analgesia between discharge and 24 h was significantly lower in the intra-articular morphine group (P = 0.038), with 4 (20%) patients in the intra-articular group and 11 (60%) patients in the intramuscular group consuming supplementary analgesia. There were no differences in plasma morphine concentrations between the groups. CONCLUSIONS: A large dose of intra-articular morphine provided better analgesia than the same dose of intramuscular morphine, low plasma morphine levels suggesting a peripheral mechanism.

Adult↗

A protective merozoite protein of Plasmodium falciparum shares an epitope with surface antigens of Paramecium.

A Plasmodium falciparum cDNA expression clone, lambdaPf9, had been identified earlier as a protective epitope, using anti-lambdaPf9 antibodies and combinatorial phagotopes. A segment of the Pf9 gene showed homology with Paramecium immobilization surface antigens such as 51B, 51A and 156G. A synthetic Pf9-peptide was designed from this region, and specific antibodies were raised. Each of these anti-Pf9 antibodies and combinatorial reagents, as well as anti-Paramecium 51B antibodies, recognized the Pf9-peptide on ELISA, and the same protein band in parasite immunoblots. The P. falciparum protein was released from the merozoite membrane fraction on treatment with PI-PLC, indicating the presence of a GPI anchor. Anti-Pf9-peptide antibodies specifically inhibited the growth of P. falciparum in culture. Immunofluorescence assays showed the reactivity of anti-Pf9-peptide sera with P. falciparum merozoites and gametocytes, as well as on the surface of Paramecium tetraurelia. The Pf9-peptide was able to induce proliferation of splenic lymphocytes obtained from mice infected with the rodent malarial parasites Plasmodium berghei and Plasmodium yoelii. These results point towards Plasmodium Pf9 as a conserved novel protective protein, sharing an epitope with Paramecium surface antigens.

Amino Acid Sequence↗

An evaluation of the modified Airway Management Device.

We evaluated the modified Airway Management Device (AMDTM) in 60 spontaneously breathing anaesthetised patients. The insertion and removal of the device was very easy and atraumatic. The airway was secured on the first attempt in 41 patients (70%; 95% CI 57-80%). The most important problem was loss of airway, which occurred in 11 patients (19%; 11-30%) during maintenance of anaesthesia. The AMD was dislodged during maintenance in one patient. There was a loss of the airway in 12 patients (20%; 12-31%); in 10, it was maintained with simple airway manoeuvres or a laryngeal mask airway and tracheal intubation was required in two patients. Ten of these patients were male and two were female; the failure rate was 33% (12-31%) among the male patients and 6% (2-22%) among the female patients. The cuff volumes ranged from 4 ml to 80 ml and cuff pressures from 6 cm H2O to 92 cm H2O. Blood was seen on removal in three patients (6%; 2-16%) and nine patients (18%; 10-30%) experienced sore throat after removal of the device.

Adult↗

A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras/MAPK.

Output from the circadian clock controls rhythmic behavior through poorly understood mechanisms. In Drosophila, null mutations of the neurofibromatosis-1 (Nf1) gene produce abnormalities of circadian rhythms in locomotor activity. Mutant flies show normal oscillations of the clock genes period (per) and timeless (tim) and of their corresponding proteins, but altered oscillations and levels of a clock-controlled reporter. Mitogen-activated protein kinase (MAPK) activity is increased in Nf1 mutants, and the circadian phenotype is rescued by loss-of-function mutations in the Ras/MAPK pathway. Thus, Nf1 signals through Ras/MAPK in Drosophila. Immunohistochemical staining revealed a circadian oscillation of phospho-MAPK in the vicinity of nerve terminals containing pigment-dispersing factor (PDF), a secreted output from clock cells, suggesting a coupling of PDF to Ras/MAPK signaling.

Alleles↗

Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock.

Circadian clock genes are expressed in the suprachiasmatic nucleus and in peripheral tissues to regulate cyclically physiological processes. Synchronization of peripheral oscillators is thought to involve humoral signals, but the mechanisms by which these are mediated and integrated are poorly understood. We report a hormone-dependent interaction of the nuclear receptors, RAR alpha and RXR alpha, with CLOCK and MOP4. These interactions negatively regulate CLOCK/MOP4:BMAL1-mediated transcriptional activation of clock gene expression in vascular cells. MOP4 exhibits a robust rhythm in the vasculature, and retinoic acid can phase shift Per2 mRNA rhythmicity in vivo and in serum-induced smooth muscle cells in vitro, providing a molecular mechanism for hormonal control of clock gene expression. We propose that circadian or periodic availability of nuclear hormones may play a critical role in resetting a peripheral vascular clock.

3T3 Cells↗

Regulation of the cycling of timeless (tim) RNA.

Circadian rhythms in Drosophila depend upon expression of the timeless (tim) and period (per) genes, which encode interacting components of the endogenous clock. These two clock genes show a robust circadian oscillation in transcription rate as well as RNA and protein levels. Transcriptional activation of both genes requires the basic helix-loop-helix (bHLH) PAS transcription factors dCLOCK (dCLK) and CYCLE (CYC), which bind E-box elements. We investigated the role of E-box elements in regulating behavioral rhythmicity and tim gene expression. We show that mutation of the upstream E-box in the tim gene prevents the rescue by tim cDNA sequences of the arrhythmic tim(01) phenotype. RNA encoded by this mutated tim transgene fails to cycle and is expressed at low levels. While a tim transgene carrying a wild-type E-box restores behavioral rhythms, tim RNA levels are intermediate to those of the mutant E-box transgenic lines and wild type, and do not display high amplitude cycling. On the other hand, high-amplitude RNA cycling was consistently obtained with a tim transgene that contains genomic, rather than cDNA, sequences. To identify additional sequences that may be required for tim cycling, we investigated the role of an E-box in the first intron of the tim gene through cell culture experiments. In these experiments, the presence of this intron did not have any effect on the activation of tim transcription by dCLK/CYC. As the upstream E-box was implicated in activation by dCLK/CYC in cell culture, we assayed sequences containing this E-box for association with proteins in fly head extracts. These studies provide the first biochemical evidence for an in vivo complex containing dCLK and CYC that binds the tim upstream sequence and is detected at all times of day. Together, these data highlight molecular mechanisms that are critical for behavioral rhythms.

ARNTL Transcription Factors↗

Postcoital vaginal laceration in a patient presenting with signs of small bowel perforation: report of a case.

Postcoital vaginal rupture or tear is a well-known entity to the gynecologist, albeit unusual; however, such cases are rarely encountered by the general surgeon. The index case is reported to highlight the rare situation wherein a middle-aged woman underwent laparotomy for a suspected small bowel perforation, which revealed a vaginal tear as the cause of pneumoperitoneum. This case emphasizes the importance of taking a gynecological history and performing a gynecological examination when the clinical diagnosis is uncertain.

Coitus↗

Role of molecular oscillations in generating behavioral rhythms in Drosophila.

Circadian oscillations of clock gene products are thought to provide time-of-day signals that drive overt rhythms. In Drosophila, RNA and protein levels of the period and timeless genes oscillate and the proteins autoregulate their transcription. To test the relevance of these oscillations, we expressed period and timeless under control of constitutively active promoters. Constitutive expression of either RNA supported protein cycling and behavioral rhythms in the respective null mutant, although constitutive timeless was less effective than constitutive period. Constitutive expression of both genes restored behavioral rhythms that showed deficits in photic resetting and drove cyclic expression of the clock-controlled RNA, vrille. Overexpression of either period or timeless, but especially timeless, attenuated behavioral rhythmicity and protein cycling in lateral neurons. We propose that the two proteins must cycle to drive rhythmic expression of downstream genes.

Animals↗

A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis.

In the fruit fly, Drosophila melanogaster, rest shares features with mammalian sleep, including prolonged immobility, decreased sensory responsiveness and a homeostatic rebound after deprivation. To understand the molecular regulation of sleep-like rest, we investigated the involvement of a candidate gene, cAMP response-element binding protein (CREB). The duration of rest was inversely related to cAMP signaling and CREB activity. Acutely blocking CREB activity in transgenic flies did not affect the clock, but increased rest rebound. CREB mutants also had a prolonged and increased homeostatic rebound. In wild types, in vivo CREB activity increased after rest deprivation and remained elevated for a 72-hour recovery period. These data indicate that cAMP signaling has a non-circadian role in waking and rest homeostasis in Drosophila.

Animals↗

The injury pattern of a new law enforcement weapon: the police bean bag.

STUDY OBJECTIVE: This case series describes the injury pattern of the police bean bag, a new weapon adopted by US law enforcement agencies. METHODS: Retrospective chart review between 1996 and 2000 identified bean bag injuries. Autopsy data were gathered for 1 fatality. Circumstances of the shootings, toxicology results, and psychiatric diagnoses, if any, were recorded. RESULTS: Thirty-nine men and 1 woman between the ages of 16 and 77 years were shot by officers of either the Los Angeles Police Department or the Los Angeles Sheriff's Department. The fatality was caused by massive hemothorax after thoracic penetration. The locations of serious penetrating injuries included the thoracic cavity, eye, abdomen, arm, and leg. Blunt injuries included splenic rupture, pneumothorax, compartment syndrome, testicular fracture, subcapsular liver hematoma, and cardiac contusion. Complications included hemothorax, pneumopericardium, wound infection, compartment syndrome, and osteomyelitis. Psychiatric consultation was requested for 27 (69.2%) of 39 surviving patients. The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) Axis I was used for diagnosis in all 27 patients. Psychosis was diagnosed in 16 (59.3%), suicidal ideation in 15 (55.6%), and major depression in 6 (22.2%) of the 27 cases. Schizophrenia had previously been diagnosed in 7 (25.9%) of the 27 cases. All but 1 of the patients had toxicology screenings performed, and the results of 29 (74.4%) of 39 were positive. Of these 29 positive results, 15 (51.7%) were positive for alcohol and 8 (27.6%) were positive for cocaine. CONCLUSION: Awareness of the broad scope of potential injuries mandates a thorough evaluation of both blunt and penetrating trauma in patients shot with police bean bags. The scope of these injuries raises significant public health considerations because use of this weapon has been adopted by law enforcement agencies in all 50 states and at least 10 countries.

Adolescent↗