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Biomedical subjects

Z Khan

Publications and source records attributed to Z Khan.

At least 19 recordsLinked to original sources

Structural, functional and therapeutic biology of survivin.

Survivin is a unique member of the inhibitor of apoptosis (IAP) protein family that interferes with post-mitochondrial events including activation of caspases. Survivin regulates cell cycle also. It is expressed in most of the human tumors, but it is barely detectable in the terminally differentiated normal cells/tissues. Molecular mechanisms of regulation of survivin in cancer are not clearly understood. Nevertheless, the functional loss of wild type p53 is often associated with upregulation of survivin. Tumors that over-express survivin generally bear a poor prognosis and are associated with resistance to therapy. The differential expression of survivin in cancer versus normal tissues makes it a useful tool in cancer diagnosis and a promising therapeutic target. A growing body of literature suggests nuclear expression of survivin as a good prognostic marker. Disruption of the survivin induction pathway has resulted in an increase in apoptosis and inhibition of tumor growth. Regular therapies, such as, radiotherapy in combination with anticancer drugs in clinical practice may yield promising results.

Humans↗

Observations on the suppression of root-knot nematode (Meloidogyne arenaria) on tomato by incorporation of cyanobacterial powder (Oscillatoria chlorina) into potting field soil.

Experiments were carried out to investigate the nematicidal potential of a cyanobacterium, Oscillatoria chlorina, against the root-knot nematode, Meloidogyne arenaria on tomato plants grown in pots filled with 500 cm3 of field soil infested with 12-s stage juveniles (J2)/cm3 soil. Incorporation of freeze-dried cyanobacterial powder into potted field soil at the rate of 0.2%, 0.4%, 0.6%, 0.8% and 1.0% (w/w) 5 days prior to tomato planting, reduced root galling, final population of M. arenaria and increased vegetative growth of tomato plants and root-mass production, compared with untreated control (P > or = 0.05). The beneficial effect of adding cyanobacterial powder into infested potted field soil increased exponentially with concentration up to 0.8%. Root galling and nematode population decreased by 68.9% and 97.6%, respectively at the highest dose (1%) of cyanobacterial powder compared with the untreated control. Addition of cyanobacterial powder into infested potted field soil at 5 days before planting was the most effective followed by 2 days before and at the time of tomato planting. We conclude that application rate and timing are important factors in the control of root-knot nematodes with O. chlorina.

Animals↗

Management of Meloidogyne incognita on tomato by root-dip treatment in culture filtrate of the blue-green alga, Microcoleus vaginatus.

The nematicidal potential of culture filtrates of the blue-green alga, Microcoleus vaginatus (Cyanobacterium) was tested against Meloidogyne incognita on tomato in pots under greenhouse conditions. Prior to the transplantation of tomato seedling, roots were dipped in different concentrations (0.2%, 0.5%, 1%, 2%, 10%, 50% and 100%) of culture filtrate of M. vaginatus for 30 min. Root-dip treatment reduced the root galling and final population of M. incognita and increased vegetative growth of plants and root-mass production compared with the control. The beneficial effect of root-dip treatment increased with the increase in the concentration of culture filtrate. Root galling and final nematode populations were reduced by 65.9% and 97.5%, respectively when treated at the highest concentration.

Animals↗

Management of vesico-vaginal fistulas in women.

OBJECTIVE: Urinary fistulas resulting from obstetric trauma remains a major problem in developing countries. Surgical success rates, however, range from 61% to 95%. This study reviews the main causes of fistulas, and the surgical techniques and success rates of surgical closure. METHOD: A total of 1086 cases of urinary fistulas resulting from obstetric trauma over 25 years were reviewed. All women received surgical intervention. Various types of fistulas as well as specific surgical techniques are described, and patient age, parity, and probable cause of fistula were compared with findings from studies in Africa. RESULTS: The highest number of cases (47.6%) occurred in women aged between 26 and 35 years; moreover, 54.43% of the women were para 6 and higher. Obstructed labor contributed to 72.78%, cesarean hysterectomy to 7.60%, cesarean section to 7.30%, and other obstetrical traumatic procedures to 12.28% of the cases. Surgical success was achieved in 84.5% of the cases. The major residual problem of stress incontinence was noted in 5% of the cases. CONCLUSION: Besides prevention, the basic principles of fistula repair are the most important factors in achieving surgical success. Better preoperative preparation and rigorous measures for preventing postoperative infection can help increase the success rate of fistula repair.

Adolescent↗

Prospective randomized controlled trial: conventional versus powered phlebectomy.

OBJECTIVES: Transilluminated powered phlebectomy (TriVex) is a new surgical technique that uses tumescent dissection, transillumination, and powered phlebectomy. The purpose of this study was to compare TriVex with conventional varicose vein surgery in terms of pain, cosmesis, recurrence, complications, and operating time. METHODS: One hundred eighty-eight limbs in 141 patients (33 men, 108 women; mean age, 42.5 years) with varicose veins were randomised to conventional (n = 100) or TriVex (n = 88). Exclusion criteria were venous ulceration or deep venous disease. Varicosities were graded with CEAP and clinical assessment (grades 1-3), and were similar in both groups. Randomization was single blinded. Long or short saphenous vein ligation or stripping was performed as indicated with duplex scanning. Operative time was from skin incision to leg bandaging. Phlebectomy was performed with conventional stab avulsions or TriVex. Patients completed assessment forms preoperatively and postoperatively (2, 6, 26, 52 weeks), and this was supplemented with physician clinical evaluation. Pain was assessed with visual analog score. RESULTS: There was a significant difference in the number of incisions for phlebectomy in the two groups (conventional, n = 29; TriVex, n = 5; P <.0001). TriVex was faster in the grade 3 (extensive) group, but this did not reach statistical significance. There was no difference in mean postoperative pain score over 8 days in the two groups (P =.4624). At 2 weeks there was no significant difference between the groups with regard to bruising (P =.77), cellulitis (P =.33), and numbness (P =.33). At 6 weeks there was no significant difference between the groups with regard to nerve injury (P =.97), residual veins (P =.79), cosmetic score (P =.837), and overall satisfaction (P =.878). At 6 and 12 months, there was no significant difference in cosmesis (P =.955, P =.088, respectively) or recurrence (P =.27, P =.11, respectively). CONCLUSIONS: TriVex is a safe and effective method for excision of varicosities and compares well, after a learning curve, with conventional surgery in regard to complications and recurrence. It has the advantage of a trend toward reduced operating time in extensive varicosities, and significantly fewer incisions, although there was no perceived difference in cosmesis during follow-up.

Adult↗

Abnormal motor behavior and vestibular dysfunction in the stargazer mouse mutant.

In stargazer mutant mice, a mutation in the gene encoding stargazin results in absence epilepsy, cerebellar ataxia, and a characteristic abnormal motor syndrome. The main goal of the current studies was to characterize the nature and source of the abnormal motor behavior. Because the stargazer motor syndrome resembles that of other rodents with vestibular dysfunction, the motor abnormalities were compared with those of normal mice treated with toxins known to damage the vestibular system. Quantitative open field assessments revealed that the stargazer mice display a motor syndrome very similar to that exhibited by mice with toxin-induced vestibulopathy. However, stargazer mice also displayed several additional behaviors, such as ataxic gait and sustained extensor movements of the neck. In addition, stargazer mice performed worse than mice with toxin-induced vestibulopathy in most standard tests of motor function. Motor function was also impaired on each of four behavioral tests sensitive to vestibular function. Because of the close associations between the vestibular and auditory systems, tests of auditory function were also employed. The stargazer mutants exhibited relatively normal auditory brainstem evoked responses but no apparent acoustic startle reflex. Histological examination of vestibular sensory epithelium at the light and electron microscopic levels confirmed the existence of abnormalities in the stargazer mutants. These results imply a previously unrecognized role for stargazin in the normal functions of the vestibular system and indicate that some, but not all, of the abnormal motor syndrome of stargazer mice can be attributed to vestibular dysfunction.

Acoustic Stimulation↗

Epidemiology of Candida colonization in an intensive care unit of a teaching hospital in Kuwait.

The incidence of Candida infections in intensive care units (ICU) is increasing. Although most cases of candidemia are caused by commensal strains colonizing the patients' own body sites, recent studies have suggested that the source of Candida infection can also be exogenous. This study was carried out to prospectively investigate the frequency of Candida colonization among patients and health care personnel of an ICU of a teaching hospital in Kuwait. A total of 57 patients and 45 nurses were investigated. Candida isolates were identified to the species level by the Vitek identification system. The typing of selected isolates was performed by randomly amplified polymorphic DNA (RAPD) using three different arbitrary primers (CARAPD1, AP3, CT5). Of the 526 samples collected from 57 patients, 180 (34%) yielded Candida species. These included 112 (62%) C. albicans, 37 (21%) C. glabrata, 15 (8%) C. parapsilosis, 11 (6%) C. tropicalis, 3 (2%) C. krusei and 2 (1%) C. lusitaniae isolates. Thirty-seven patients (65%) were colonized by Candida at some point of stay in the ICU. Seven (12%) patients yielded more than one Candida species from the sites/specimens tested. The frequency of Candida isolation was highest from oropharynx, followed by rectum, groin, urine and trachea. Twenty-five (6%) of the 448 swabs from the nurses yielded Candida and included C. albicans (n = 16), C. parapsilosis (n = 4) and C. famata (n = 5). While all the three primers yielded varying patterns in RAPD analyses for each Candida species, the results obtained by AP3 were most discriminatory. The data showed that the colonizing Candida isolates recovered from various body sites of the patients, as well as the nursing staff, were different. However, when RAPD profiles of three blood culture isolates from candidemic patients were analyzed, the DNA fingerprint produced by one C. parapsilosis blood culture isolate was similar to C. parapsilosis recovered from the hands of two nurses, suggesting exogenous acquisition of infection.

Adolescent↗

Variation in intubation decisions for patients with chronic obstructive pulmonary disease in one critical care network.

BACKGROUND: Anecdotal evidence suggests variation in intubation decisions for chronic obstructive pulmonary disease (COPD) patients with respiratory failure, but little is known about the extent of or reasons for this variability. AIM: To describe clinician decision-making for patients with exacerbations of COPD considered for intubation. DESIGN: Telephone simulation study. METHODS: Consultants responsible for COPD admissions in the Heart of England Critical Care network were asked to decide whether or not to admit three patients with COPD to ICU on the basis of information conveyed over the telephone. Consultants were also asked to predict patients survival in ICU hospital and at 180 days on the assumption that the patient did receive ICU care. RESULTS: Of the 120 consultants, 98 (82%) took part; 89% would admit patient 1, 64% patient 2, and 40% patient 3. The prediction of survival if ICU admission had occurred differed significantly between admitters and non-admitters. Mean predicted post-ICU hospital survival for patient 1 was 46% (95%CI 43-49) for admitters, and 13% (95%CI 6-19) for non-admitters (p < 0.001). The respective figures for patient 2 were 38% (95%CI 34-42) vs. 12% (95%CI 8-15) (p < 0.001), and for patient 3, 28% (95%CI 24-33) vs. 13% (95%CI 10-16) (p < 0.001). For a housebound COPD patient in their mid 70s, the mean (SD) threshold of predicted hospital survival below which consultants would recommend not admitting to ICU was 22% (13.2%). CONCLUSIONS: Consultants differed markedly in their admitting decisions about identical patients. Objective outcome prediction models might improve equity in ICU bed use for patients with COPD.

Aged↗

HPV16/18 prevalence in cervical lesions/cancers and p53 genotypes in cervical cancer patients from India.

OBJECTIVES: The HPV16/18 code for an oncoprotein-E6, which binds to p53 tumor suppressor protein and degrades the protein via ubiquitination. A common polymorphism of p53 in exon 4 codon 72, resulting in either proline (Pro) or arginine (Arg), affects HPV16/18 E6-mediated degradation of p53 protein in vivo. Hence, in the current study we investigated the prevalence of HPV16/18 in cervical lesions and the distribution of p53 genotypes in cervical cancers and normal healthy women. METHODS: DNA from 337 Indian women with invasive cervical cancers, 164 women with clinically normal cervix, 64 women with low-grade squamous intraepithelial lesions (LSIL), and 5 women with high-grade squamous intraepithelial lesions (HSIL) was examined for the presence of HPV16/18 using consensus primers in a polymerase chain reaction (PCR), and the specific HPV type was identified by Southern hybridization of the PCR product using HPV16/18 type-specific nucleotide sequences as probes. Further, 134 women with cervical cancers and 131 healthy women were used to determine the frequency of p53 genotypes, Pro/Pro, Arg/Arg, and Pro/Arg, using peripheral blood cell DNA to indicate the constitutional genotypes and allele-specific primers, in a PCR-based assay. RESULTS: We observed a prevalence of HPV16/18 in 77% (258/337) of cervical cancer patients, 38% (24/64) of LSILs, 4 of 5 HSILs, and 15.2% (25/164) of normal healthy women. The frequency of distribution of the three genotypes of p53 codon 72 in a subgroup of the HPV16/18-positive cervical cancer patients was Pro/Pro 0.18 and Arg/Arg 0.26, with the heterozygous Pro/Arg 0.56, differing significantly from the genotype frequency in the normal healthy women (chi(2) = 6.928, df = 2, P < 0.05). CONCLUSIONS: A high prevalence of HPV16/18 was observed in the cervical cancers. The prevalence in LSILs confirms HPV16/18 infection as an early event and further indicates a role in progression of lesions. The p53 genotype distribution indicated that women homozygous for Arg genotype were at a 2.4-fold higher risk for developing HPV16/18-associated cervical carcinomas, compared to those showing heterozygous Pro/Arg genotype (odds ratio 2.4, 95% confidence interval 1.89 to 3.04).

Arginine↗

The non-immunosuppressive immunophilin ligand GPI-1046 potently stimulates regenerating axon growth from adult mouse dorsal root ganglia cultured in Matrigel.

We used explant cultures of adult mouse dorsal root ganglia with spinal nerve attached growing in Matrigel to assess the effects of the non-immunosuppressive immunophilin ligand GPI-1046 [Snyder et al. (1998) TIPS 19, 21-26] on the growth rate of regenerating sensory axons and found a potent stimulation of axon growth. In these explant cultures, naked, unfasciculated axons emerge from the cut end of the spinal nerve and continue to grow in the Matrigel for up to eight days [Tonge et al. (1996) Neuroscience 73, 541-551]. Some axons are entirely smooth whilst others show prominent varicosities. Some of the former express the phosphorylated neurofilament epitope recognised by monoclonal antibody RT97, a marker for large calibre, myelinated axons, whilst the latter express calcitonin gene-related peptide, predominantly a marker for unmyelinated, and small diameter myelinated sensory axons. Many of the axons in these cultures also express the low-affinity neurotrophin receptor p75. GPI-1046 has been shown to have striking stimulatory effects on embryonic primary sensory axons growing in vitro and it was therefore of interest to see whether it could also enhance regenerating sensory axon growth from the adult ganglia in our cultures. GPI-1046 potently stimulated axon growth in our cultures in a dose-dependent manner. The stimulatory effect was not dependent on the class of sensory axon. These observations show that GPI-1046 is a potent stimulator of regenerating axons from adult, primary sensory neurones. The cellular site of action of GPI-1046 is unknown. To distinguish between a direct effect of the drug on neurones and an indirect effect we compared the effects of GPI-1046 on explant and dissociated cultures. In confirmation of previous results, we found that GPI-1046 potently stimulated axon outgrowth from explants of embryonic chick dorsal root ganglia. However, the drug was without effect on dissociated embryonic dorsal root ganglion neurones, suggesting that non-neuronal cells are important for axon growth stimulation.

Animals↗

Use of the 'nutriceutical', bovine colostrum, for the treatment of distal colitis: results from an initial study.

BACKGROUND: Bovine colostrum is a rich source of nutrients, antibodies and growth factors. AIM: To examine the efficacy of colostrum enemas in the treatment of distal colitis using a randomized, double-blind, controlled protocol. METHODS: Fourteen patients (eight female), with a mean age of 45 years (range, 16-75 years) and mild to moderately severe distal colitis (Powell-Tuck scoring system), received colostrum enema (100 mL of 10% solution) or placebo (albumin solution) b.d. for 4 weeks. Both groups also received mesalazine (1.6 g/day) or, if already taking it, had a dose increment of 1.6 g/day. Disease activity was documented at 0, 2 and 4 weeks. RESULTS: After 4 weeks, the colostrum group showed a mean reduction in symptom score of - 2.9 (95% confidence interval (CI), - 5.4 to - 0.3), whereas the placebo group showed a mean response of + 0.5 (95% CI, - 2.4 to +3.4). The histological score improved in five of the eight patients in the colostrum group (mean response, - 0.9; 95% CI, - 1.69 to - 0.03), whereas the histological scores only improved in two of the six patients in the placebo group (mean response, 0.2; 95% CI, - 2.4 to +2.6). CONCLUSIONS: Bovine colostrum enema shows potential as a novel therapy for left-sided colitis with additional benefits over using mesalazine alone. Further studies appear to be warranted.

Adolescent↗

Does Helicobacter pylori eradication reduce the long-term requirements for acid suppressants in patients with a history of peptic ulcer disease in general practice? Results from a four-year longitudinal study.

BACKGROUND: Acid suppressants, especially proton-pump inhibitors, are major contributors to the drug costs in primary care. Although Helicobacter pylori eradication reduces peptic ulcer relapse, some studies suggest that patients may remain symptomatic and continue to require acid-suppressant therapy. METHODS: We identified all patients taking long-term acid suppressants in a large primary health care clinic to determine the proportion who had peptic ulcer disease and to examine the effect of H. pylori eradication on their long-term requirement for acid suppressants. RESULTS: 126/394 patients taking long-term acid suppressants had a definite diagnosis of peptic ulcer. Of these 126 patients, 60 were considered appropriate for the study. At Stage 1 (May 1994), all patients were tested for H. pylori infection and positive patients (60/66) received eradication therapy with omeprazole 20 mg bd and amoxycillin (1 gm bd) or clarithromycin (500 mg tds) for 2 weeks. Six weeks later (Stage 2) patients, requirements for continued acid-suppressant treatment were determined and previously positive subjects retested using the 13C urea breath rest. This showed that 70% (42/60) had been successfully eradicated. One year later (Stage 3), 44% (18/41) of the patients successfully eradicated still required acid suppressants. The majority of these patients (11/18; 61%) continued to remain on acid-suppressant treatment at 4 years (Stage 4) (95% CI 38%, 83%). CONCLUSIONS: We found that about 1/3 of all patients on long-term acid-suppressant therapy in General Practice had a confirmed diagnosis of peptic ulcer disease. Despite successful eradication treatment for H. pylori at the start of the study, about half of these patients still used acid suppressants after 1 year and 1/4 patients (11/41) in this group continued to remain on acid-suppressant treatment for another 3 years.

Amoxicillin↗

Detection of Y chromosome-specific DNA in the plasma and urine of pregnant women using nested polymerase chain reaction.

The present study was undertaken to evaluate a nested polymerase chain reaction (PCR) for detection of Y chromosome-specific fetal DNA in maternal plasma and urine of pregnant women during different gestational stages. DNA isolated from plasma and urine samples of 80 pregnant women (between 7 and 40 weeks' gestation) underwent amplification for Y chromosome-specific 198 bp DNA by nested PCR. The postpartum analysis of fetal gender showed that 55 women carried male and 25 female fetuses. Among the 55 women bearing male fetuses, Y chromosome-specific signals were detected in 53 (96%) plasma and 21 (38%) urine samples. Moreover, out of 25 women bearing female fetuses, 3 (12%) and 1 (4%) women had Y chromosome-specific signal in plasma and urine, respectively. Analysis of results with respect to gestational age revealed that there was no significant difference in the detection of Y chromosome-specific DNA between different trimesters in maternal plasma of women bearing male fetuses. These results showed that fetus-specific DNA was detected with high sensitivity (96%) and specificity (88%) in the maternal plasma by nested PCR, and therefore the method could be useful as a non-invasive procedure for fetal sex determination and prenatal diagnosis.

Adult↗

Spectral karyotyping study of chromosome abnormalities in human leukemia.

Chromosomal analysis plays an important role in the diagnosis, treatment and prognosis of human leukemia. Currently, the GTG-banding technique (G-banding) is the most commonly used diagnostic method in clinical cytogenetics. G-banding analysis of subtle chromosomal rearrangements or complex karyotypes with multiple markers can be inadequate because of poor chromosome morphology and/or an insufficient yield of analyzable metaphases. Fluorescence in situ hybridization (FISH) is a highly sensitive and specific method to detect chromosomal alterations. Conventional FISH is used optimally in instances where only one or a few abnormalities are investigated. Spectral karyotyping (SKY), a novel cytogenetic technique, has been developed to unambiguously display and identify all chromosomes at one time using a spectrum of 24 different colors. This report presents the use of SKY for examination of the entire karyotype in specimens with complex chromosomal abnormalities from three leukemia patients. Conventional cytogenetic analysis (G-banding) showed complex hyperdiploid clones with multiple markers in each case. SKY was able to clarify and identify additional cryptic chromosomal translocations [e.g., t(2;10), t(3;10), t(5;7), t(7;18), t(9;17), t(10;12), t(13;16)] insertions [e.g., ins(17;9), ins(20;Y)], duplications [e.g., i(8)(q10), dup(4)(q31q35)] and marker chromosomes in each case. This study demonstrates that the combination of SKY and G-band techniques results in a more complete characterization of the complex chromosomal aberrations seen in leukemia.

Bone Marrow Cells↗