Cervical vertebrae maturity.
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Body Height↗
Biomedical subjects
A Gupta
Publications and source records attributed to A Gupta.
Mapping of hiv-1 Gag epitopes recognized by polyclonal antibodies using gene-fragment phage display system.
Phage display has emerged as a powerful technique for mapping epitopes recognised by monoclonal and polyclonal antibodies. We have recently developed a simple gene-fragment phage display system and have shown its utility in mapping epitope recognised by a monoclonal antibody. In the present study, we have employed this system in mapping epitopes recognised by polyclonal antibodies raised against HIV-1 capsid protein, p24 which is derived from proteolytic cleavage of Gag polyprotein. HIV-1 gag DNA was fragmented by DNase I and the fragments (50-250 bp) were cloned into gene-fragment phage display vector to construct a library of phages displaying peptides. This phage library was used for affinity selection of phages displaying epitopes recognised by rabbit anti-p24 polyclonal antibodies. Selected phages contained sequences from two discrete regions of p24, demonstrating the presence of two antigenic regions. The DNA sequences encoding these regions were also cloned and expressed as GST fusion proteins. The immunoreactivity of these epitopes as GST fusion proteins, or as phage-displayed peptides, was comparable in ELISA system using same anti-p24 polyclonal antibodies. The results indicate that the gene-fragment based phage display system can be used efficiently to identify epitopes recognised by polyclonal antibodies, and phage displayed epitopes can be directly employed in ELISA to detect antibodies.
Animals↗
Management of hypertension in primary care.
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Adult↗
Etiology and chemoprevention of esophageal squamous cell carcinoma.
Squamous cell carcinoma (SCC) of the human esophagus has a multifactorial etiology involving several environmental and/or genetic factors. Current modalities of therapy for this disease offer poor survival and cure rates. Although a number of approaches could be undertaken to reduce the occurrence of esophageal SCC, including changes in lifestyle and improved nutrition, such approaches are not easily implemented. Chemoprevention offers a viable alternative that is likely to be effective against this disease. Clinical investigations in areas of high incidence of esophageal SCC have shown that primary chemoprevention of this disease is feasible, if potent inhibitors are identified. Studies in the Fischer 344 rat model of nitrosamine-induced tumorigenesis have proven valuable in understanding the biology of esophageal SCCs and help identify surrogate end-point biomarkers and putative agents that can be useful in human chemoprevention studies. Several compounds that inhibit tumor initiation by suspected human esophageal carcinogens have been identified using this model. These include diallyl sulfide, isothiocyanates and several polyphenolic compounds. Novel biomarkers, including nuclear/nucleolar morphometry using computer-assisted image analysis of preneoplastic lesions, have been developed to measure efficacy of chemopreventive agents against esophageal SCC. The identification of single agents that inhibit the progression of dysplastic lesions, however, has proven difficult. Results from a food-based approach suggest that the use of freeze-dried berry preparations can affect both initiation and promotion/progression of esophageal SCC in an animal model. These observations provide valuable information for future studies on chemoprevention of cancers of the esophagus in a clinical setting. Given the complex etiology of esophageal SCC, it is felt that the most effective chemoprevention strategies would include agents that reduce mutational events associated with carcinogen exposure in combination with agents that inhibit the progression of intraepithelial dysplasia to invasive cancer.
Animals↗
Pulse cyclophosphamide therapy in frequently relapsing nephrotic syndrome.
BACKGROUND: The treatment of frequently relapsing (FR) and steroid-dependent (SD) idiopathic nephrotic syndrome (INS) with oral cyclophosphamide (OCP) poses problems of compliance, side-effects and infections. METHODS: We prospectively evaluated the usefulness of intravenous cyclophosphamide (IVCP) in children with steroid sensitive INS who were frequent relapsers or steroid dependent. Fifty-one children were included in the study of whom 22 were FR and 29 were SD. IVCP was administered in a dose of 500 mg/m(2)/month for 6 months after achieving a steroid-induced remission. The response to IVCP was evaluated in terms of remission, change in the steroid response status of the patient, duration of remission (i.e. proteinuria-free days), side effects and compliance with therapy. RESULTS: The proteinuria-free days (mean 19.9+/-3.5 before IVCP therapy vs 1256+/-167 days after IVCP therapy) (P<0.00001), and serum albumin levels (23+/-1.6 g/l before IVCP therapy vs 34+/-2 g/l after IVCP therapy) (P<0.001) were significantly higher following IVCP therapy. The cumulative remission rate in the study group was 49% at 5 years and was comparable to that achieved with oral cyclophosphamide at a 40% lower cumulative dose. CONCLUSIONS: We conclude that IVCP is a safe and effective therapeutic modality in children with INS who are FR and SD. Its efficacy is comparable to the results obtained with oral cyclophosphamide based on historical comparisons with previous studies.
Adolescent↗
Renal bone disease in black dialysis patients: are algorithms developed for white dialysis patients valid?
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Black or African American↗
Changing antibiotic sensitivity in enteric fever.
Emergence of drug resistance in enteric fever is a major concern for the clinician. All children hospitalized with enteric fever during the period 1 March to 31 May 2000 were studied prospectively for their clinical presentation and response to therapy, and an attempt was made to compare these results with the results of hospitalized children with enteric fever during a similar period in the years 1990 and 1995. The results revealed that there was a significant change in the response to antibiotic therapy as evidenced by significant resistance to ciprofloxacin (55.5 per cent) and early evidence of emerging drug resistance to ceftriaxone (4.4 per cent). Although the sample size was small and had its limitations, the results also pointed towards the re-emergence of sensitivity to chloramphenicol.
Age Distribution↗
A systematic review of the peripheral analgesic effects of intraarticular morphine.
The analgesic effects of intraarticular morphine are controversial. To systematically evaluate the effects, we performed a review of the literature and a metaanalysis of the peripheral effects of morphine injected intraarticularly. Research databases were searched to identify articles in which peripheral analgesic effects of morphine were studied in patients undergoing arthroscopic knee procedures under local, regional, or general anesthesia. The review was performed on three issues: does morphine injected intraarticularly produce analgesia, is it a dose-dependent effect, and, if so, is the effect systemic or mediated via peripheral opioid receptors? Visual analog score (VAS) and analgesic consumption were studied during the early phase (0-2 h), intermediate phase (2-6 h), and late phase (6-24 h) postoperatively after injection of morphine intraarticularly. Metaanalysis of these effect variables was performed by the weighted-analysis technique, and the essential homogeneity assumption was tested by the chi(2) test. Forty-five articles could be identified in which the effects of morphine were studied in a prospective, randomized manner, and 32 of these studies included a placebo control. Pooled analyses of data from 19 studies suitable for metaanalysis showed an improvement in analgesia after morphine compared with placebo in the order of 12-17 mm on the VAS during all three phases of treatment. Studies with high quality scores showed somewhat smaller improvements. Total analgesic consumption could not be analyzed statistically, but the number of studies showing decreased analgesic consumption or no differences between groups was identical (six and six). No clear dose-response effect was seen when VAS was used as a measure of pain, but it was seen when area under the curve was used as a measure of pain. A systemic effect of peripherally-injected morphine was not possible to exclude because of the very limited data available. We conclude from this metaanalysis that intraarticularly administered morphine has a definite but mild analgesic effect. It may be dose dependent, and a systemic effect cannot be completely excluded.
Analgesics, Opioid↗
Intracameral amphotericin B: initial experience in severe keratomycosis.
PURPOSE: Fungal keratitis is a significant cause of ocular morbidity in India. The most commonly implicated fungi are Aspergillus spp. Patients often present with hypopyon, which usually contains fungal elements. The treatment is difficult owing to poor intraocular penetration of most available antifungal agents. This study evaluated the results of intracameral injection of amphotericin B in natamycin resistant cases of severe keratomycosis. METHODS: Three patients of culture proven Aspergillus flavus corneal ulcer with hypopyon not responding to topical natamycin 5%, amphotericin B 0.15%, and oral itraconazole were administered intracameral amphotericin B. The first case received 7.5 microg in 0.1 mL followed by two subsequent injections of 10 microg in 0.1 mL each, the second case received two injections of 10 microg in 0.1 mL, and the third patient received a single dose of 10 microg in 0.1 mL. Culture of the aqueous sample also grew A. flavus in all three cases. RESULTS: All three cases responded favorably, with the ulcer and hypopyon clearing completely. There was no clinical evidence of corneal or lenticular toxicity in any patient. CONCLUSIONS: Intracameral amphotericin B may be a useful modality in the treatment of severe keratomycosis not responding to topical natamycin. It ensures adequate drug delivery into the anterior chamber and may be especially useful to avoid surgical intervention in the acute stage of the disease.
Adult↗
Endoscopic inferior turbinate reduction: an outcomes analysis.
OBJECTIVES/HYPOTHESIS: In a previous publication, we introduced an endoscopic technique for the treatment of nasal obstruction caused by inferior turbinate hypertrophy. The technique, a modification of the procedure popularized by Mabry, involves resecting the inferior and lateral aspects of the inferior turbinate with a microdebrider under endoscopic guidance. Our preliminary postoperative results were favorable. All 20 patients experienced improvement by postoperative day 5 and the incidence of complications over the first 6 months after surgery was low. The objective of this study is to perform a long-term outcomes analysis of patients undergoing the procedure. STUDY DESIGN: Follow-up survey questionnaire and analysis. METHODS: We sent questionnaires to 60 patients, ranging from 6 to 40 months after surgery, inquiring about continued use of nasal medications, need for further surgery, presence of adverse effects, and improvement in symptoms. Nasal airway obstruction was assessed on a subjective scoring scale from 1 (no obstruction) to 6 (complete obstruction). RESULTS: Of the 28 (47%) patients who returned questionnaires, the severity of daytime nasal obstruction was rated as 2.3 and nighttime nasal obstruction as 2.7. The use of nasal steroids and oral decongestants was 25% and 21%, respectively. Adverse effects were minimal and all but one patient (96%) experienced improvement in their nasal airway. CONCLUSION: These results confirm the long-term effectiveness of this procedure for the relief of nasal obstruction.
Endoscopy↗
Reconstructive management of cranial base defects after tumor ablation.
Successful reconstruction after cranial base tumor ablation is paramount in preventing potentially life-threatening complications. The purpose of this study was to evaluate experiences of cranial base reconstruction and to identify reconstructive management principles that may assist in achieving successful cranial base reconstruction. All cranial base reconstructions performed by the Department of Plastic Surgery at the University of Texas M. D. Anderson Cancer Center between January of 1993 and September of 1999 were reviewed. Analyses were performed to assess the impact of location of defect, type of reconstruction, type of dural repair, and history of preoperative radiation and chemotherapy on rates of complications, and patient survival. The 77 patients who underwent cranial base reconstruction after tumor ablation during the study period had a mean age of 52 years (6 to 84 years). The mean follow-up period was 28.7 months (1 to 76 months). Squamous cell carcinoma, the most common histopathologic type, was present in 24 patients (31 percent), and 35 patients (45 percent) presented with recurrent disease. Location of defects involved region I (anterior) in 31 patients (40 percent), region II (anterior-lateral) in 18 (23 percent), region III (lateral-posterior) in six (8 percent), and more than one region in 22 (29 percent). Reconstructive methods included free flaps in 52 patients (68 percent), temporalis muscle flaps in 14 (18 percent), pericranial flaps in eight (10 percent), and other local flaps (two galeal, one scalp) in three (4 percent). Of the 52 free flaps, 18 (35 percent) were used in region I, 14 (27 percent) in region II, six (12 percent) in region III, and 14 (27 percent) in defects involving more than one region. Of the 14 temporalis muscle flaps, 13 (93 percent) were used for defects involving regions I or II and one (7 percent) was used for a defect involving region III. Of the 11 pericranial and other local flaps, nine (82 percent) were used in region I, one (9 percent) in region II, and one (9 percent) in a combination of regions II and III. Complications occurred in 21 patients (27 percent): three total flap losses (4 percent), three partial flap losses (4 percent), two cerebrospinal fluid leaks (3 percent), two cases of meningitis (3 percent), two abscesses (3 percent), five cases of delayed wound healing (6 percent), two hematomas (3 percent), one wound infection (1 percent), and one cerebrovascular accident (1 percent). Overall survival was 77 percent at 2 years and 58 percent at 4 years. The type of reconstruction, location of defect, type of dural repair, and history of preoperative radiation and chemotherapy had no significant association with the incidence of complications. Neither the type of reconstruction nor the location of defect showed a significant effect on patient survival. In this experience, local flaps, such as pericranial or temporalis muscle flaps, are good choices for reconstruction of smaller anterior or lateral cranial base defects. For defects that require larger amounts of soft tissue, free flaps are appropriate. With proper patient selection, successful cranial base reconstruction can be performed with either local or free flaps with a low incidence of complications.
Adolescent↗
Comparison of immediate and delayed free TRAM flap breast reconstruction in patients receiving postmastectomy radiation therapy.
Tumor pathologic features and the extent of nodal involvement dictate whether radiation therapy is given after mastectomy for breast cancer. It is generally well accepted that radiation negatively influences the outcome of implant-based breast reconstruction. However, the long-term effect of radiation therapy on the outcome of breast reconstruction with the free transverse rectus abdominis myocutaneous (TRAM) flap is still unclear. For patients who need postmastectomy radiation therapy, the optimal timing of TRAM flap reconstruction is controversial. This study compares the outcome of immediate and delayed free TRAM flap breast reconstruction in patients who received postmastectomy radiation therapy. All patients at The University of Texas M. D. Anderson Cancer Center who received postmastectomy radiation therapy and who also underwent free TRAM flap breast reconstruction between January of 1988 and December of 1998 were included in the study. Patients who received radiation therapy before delayed TRAM flap reconstruction were compared with patients who underwent immediate TRAM flap reconstruction before radiation therapy. Early and late complications were compared between the two groups. Early complications included vessel thrombosis, partial or total flap loss, mastectomy skin flap necrosis, and local wound-healing problems, whereas late complications included fat necrosis, volume loss, and flap contracture of free TRAM breast mounds. Late complications were evaluated at least 1 year after the completion of radiation therapy for patients who had delayed reconstruction and at least 1 year after reconstruction for patients who had immediate reconstruction. During the study period, 32 patients had immediate TRAM flap reconstruction before radiation therapy and 70 patients had radiation therapy before TRAM flap reconstruction. Mean follow-up times for the immediate reconstruction and delayed reconstruction groups were 3 and 5 years, respectively. The mean radiation dose was 50 Gy in the immediate reconstruction group and 51 Gy in the delayed reconstruction group. One complete flap loss occurred in the delayed reconstruction group, and no flap loss occurred in the immediate reconstruction group. The incidence of early complications did not differ significantly between the two groups. However, the incidence of late complications was significantly higher in the immediate reconstruction group than in the delayed reconstruction group (87.5 percent versus 8.6 percent; p = 0.000). Nine patients (28 percent) in the immediate reconstruction group required an additional flap to correct the distorted contour from flap shrinkage and severe flap contraction. These findings indicate that, in patients who are candidates for free TRAM flap breast reconstruction and need postmastectomy radiation therapy, reconstruction should be delayed until radiation therapy is complete.
Breast Neoplasms↗
PCR-positive tubercular retinal vasculitis: clinical characteristics and management.
BACKGROUND: Inflammation of retinal vessels is a known association of systemic tuberculosis. Patients with retinal vasculitis are subjected to extensive but unrewarding systemic workup. Polymerase chain reaction (PCR) is now commonly used to detect DNA of infective organisms including Mycobacterium tuberculosis. This study was undertaken to characterize the clinical characteristics of PCR-positive tubercular retinal vasculitis, so as to determine the clinical presentation, associated systemic features, management, and course of this form of vasculitis. METHODS: The clinical records of 13 patients seen between 1997 and 1999 with the diagnosis of PCR-positive tubercular retinal vasculitis from the aqueous or vitreous humor were reviewed. Recorded data included age, sex, race, visual acuity, anterior and posterior segment findings, and results of diagnostic evaluations. All received antituberculosis therapy with or without concomitant corticosteroids. Laser scatter photocoagulation was done in eyes with neovascularization. One eye with vitreous hemorrhage was subjected to pars plana vitrectomy. RESULTS: There were 9 (69.2%) male and 4 (30.7%) female patients with a median age of 20 years. The disease was bilateral in seven. The most consistent finding was the presence of vitritis in all the eyes followed by vitreous snowball opacities in 17 eyes (89.4%), neovascularization in 11 eyes (57.8%), retinal hemorrhages in 10 eyes (52.6%), neuroretinitis in 10 eyes (52.6%), focal choroiditis in 9 eyes (47.3%), vitreous/preretinal hemorrhage in 5 eyes (26.3%), and serous retinal detachment in 3 eyes (15.7%). Over a median follow-up of 12 months, all showed resolution of vasculitis with no recurrences. CONCLUSIONS: Polymerase chain reaction-positive tubercular retinal vasculitis had varied associated fundus findings. Its recognition is important so as to order only relevant diagnostic tests.
Adolescent↗
Bowen-Conradi syndrome in an Indian infant: first non Hutterite case.
An Indian male infant with the lethal Bowen Conradi syndrome is described. This is the first case in the literature who is not from the Hutterite population.
Abnormalities, Multiple↗
Diversity of silver resistance genes in IncH incompatibility group plasmids.
Silver compounds are used as antimicrobial agents in medicine and bacteria that develop resistance to silver cations (Ag(+)) pose problems similar to those of antibiotic-resistant bacteria. The first set of Ag(+) resistance genes (sil) was from plasmid pMG101, now assigned to the IncHI incompatibility group. Questions of whether sil genes are unique to pMG101 or are more widely found, and whether they are associated with a specific incompatibility group or occur in many plasmid groups and on bacterial chromosomes were addressed. sil genes were identified in five IncH plasmids, but not in plasmids of the IncP incompatibility group. Three sil genes (silP, silR and silE) from these plasmids were PCR-amplified, cloned, sequenced and compared to those of pMG101. Differences of 0-50 nt per kb of sequence were found. Predicted gene products were 0-6% different in amino acid sequence, but the differences did not alter residues thought to be involved in protein function (see supplementary data at http://mic.sgmjournals.org or http://www.uic.edu/depts/mcmi/individual/gupta/index.htm). For representative IncH plasmid R476b and pMG101 the effects of Ag(+) exposure on resistance levels were measured by growth. The inducibility of silC, silR and silE gene expression after Ag(+) exposure was studied by reverse transcriptase (RT)-PCR. Silver resistance increased after Ag(+) exposure for strains carrying plasmid R476b. silC and silE expression from R476b was inducible after Ag(+) exposure and was constitutive and high from pMG101. The mRNA levels for the regulatory gene silR was constitutive for both pMG101 and R476b. Close homologues for silABC(ORF96)RS from pMG101 are clustered on the chromosomes of Escherichia coli strains K-12 and O157:H7, without contiguous silP and silE homologues. Insertion deletions of the E. coli K-12 chromosomal homologues for silA and silP gave Ag(+) hypersensitivity for growth. The silA homologue knockout was complemented back to wild-type resistance by the same gene cloned on a plasmid. Homologues of sil genes have also been identified on other enterobacterial genomes.
Anti-Bacterial Agents↗
Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN.
A high-throughput, retrovirus-mediated mutagenesis method based on gene trapping in embryonic stem cells was used to identify a novel mouse gene. The human ortholog encodes a transmembrane protein containing five extracellular immunoglobulin-like domains that is structurally related to human NEPHRIN, a protein associated with congenital nephrotic syndrome. Northern analysis revealed wide expression in humans and mice, with highest expression in kidney. Based on similarity to NEPHRIN and abundant expression in kidney, this protein was designated NEPH1 and embryonic stem cells containing the retroviral insertion in the Neph1 locus were used to generate mutant mice. Analysis of kidney RNA from Neph1(-/-) mice showed that the retroviral insertion disrupted expression of Neph1 transcripts. Neph1(-/-) pups were represented at the expected normal Mendelian ratios at 1 to 3 days of age but at only 10% of the expected frequency at 10 to 12 days after birth, suggesting an early postnatal lethality. The Neph1(-/-) animals that survived beyond the first week of life were sickly and small but without edema, and all died between 3 and 8 weeks of age. Proteinuria ranging from 300 to 2,000 mg/dl was present in all Neph1(-/-) mice. Electron microscopy demonstrated NEPH1 expression in glomerular podocytes and revealed effacement of podocyte foot processes in Neph1(-/-) mice. These findings suggest that NEPH1, like NEPHRIN, may play an important role in maintaining the structure of the filtration barrier that prevents proteins from freely entering the glomerular urinary space.
Amino Acid Sequence↗
Electrophysiologic and antiarrhythmic effects of the new class III antiarrhythmic drug KCB-328 in experimental canine atrial flutter.
BACKGROUND: The electrophysiologic and antiarrhythmic effects of a new class III antiarrhythmic drug (KCB-328), a delayed rectifier potassium current (IKr) blocker with minimal reverse use-dependent effect on atrial repolarization, were evaluated in the canine night atrial crush-injury model of atrial flutter (AFL). METHODS: Ten anesthetized, open-chest dogs, were studied after right atrial crush-injury. Atrial effective refractory period (ERP), conduction velocity (CV), wavelength, and dispersion of refractoriness were determined during programmed stimulation (S1S2 at S1S1 = 200, 300, 400, and 500 msec) at four sites via a mapping plaque sutured on the right atrial free wall. Right and left ventricular ERP were similarly measured at single sites. Electrophysiological parameters were determined at baseline and following sequential cumulative doses of KCB-328 (10, 30, 100, and 300 microg/kg). RESULTS: Sustained AFL was inducible in 7/10 dogs by rapid pacing following baseline electrophysiologic measurements. KCB-328 significantly prolonged sinus cycle length, but had no effect on PR interval, and prolonged QTc only at the highest dose level. KCB-328 significantly prolonged atrial ERP and wavelength and ventricular ERP, and significantly reduced dispersion of atrial refractoriness. KCB-328 significantly prolonged AFL cycle length, and increasing doses progressively terminated sustained AFL and prevented its reinduction by pacing. No adverse hemodynamic or ventricular proarrhythmic effects were observed. CONCLUSIONS: The electrophysiologic profile of KCB-328 in this canine model of AFL, particularly its lack of reverse use-dependent effect on atrial refractoriness, suggests that it may have significant antiarrhythmic potential in treatment of atrial arrhythmias.
Animals↗