Search PubMed⌕ Search

Biomedical subjects

R Khan

Publications and source records attributed to R Khan.

At least 19 recordsLinked to original sources

Reef-coral proteins as visual, non-destructive reporters for plant transformation.

Recently, five novel fluorescent proteins have been isolated from non-bioluminescent species of reef-coral organisms and have been made available through ClonTech. They are AmCyan, AsRed, DsRed, ZsGreen and ZsYellow. These proteins are valuable as reporters for transformation because they do not require a substrate or external co-factor to emit fluorescence and can be tested in vivo without destruction of the tissue under study. We have evaluated them in a large range of plants, both monocots and dicots, and our results indicate that they are valuable reporting tools for transformation in a wide variety of crops. We report here their successful expression in wheat, maize, barley, rice, banana, onion, soybean, cotton, tobacco, potato and tomato. Transient expression could be observed as early as 24 h after DNA delivery in some cases, allowing for very clear visualization of individually transformed cells. Stable transgenic events were generated, using mannose, kanamycin or hygromycin selection. Transgenic plants were phenotypically normal, showing a wide range of fluorescence levels, and were fertile. Expression of AmCyan, ZsGreen and AsRed was visible in maize T1 seeds, allowing visual segregation to more than 99% accuracy. The excitation and emission wavelengths of some of these proteins are significantly different; the difference is enough for the simultaneous visualization of cells transformed with more than one of the fluorescent proteins. These proteins will become useful tools for transformation optimization and other studies. The wide variety of plants successfully tested demonstrates that these proteins will potentially find broad use in plant biology.

Anthozoa↗

Impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD) over a five-year period in a district general hospital.

The impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD), over a five-year period between 1995 and 2000, were studied in the Preston Acute Hospitals Trust. In 1996 the policy was changed in the Preston Acute Hospitals Trust from cefotaxime to ceftriaxone for initial treatment of severe sepsis or pneumonia in medical patients. Over the next nine months the average number of patients with C. difficile toxin-positive stools per quarter increased from 16 to 39. The predicted use of ceftriaxone exceeded by 65% an estimate based on prior use of cefotaxime. A policy of restricted duration of ceftriaxone was introduced, and although this reduced usage by over 50%, CDAD continued at an average of 9.2 cases per month, despite withdrawal of oral cephalosporins in December 1998. In August 1999 levofloxacin was substituted for ceftriaxone in the policy. The incidence of CDAD fell progressively to five cases per month by 2000. It would appear that a short (typically three dose) course of third-generation cephalosporin poses a similar risk for CDAD as a more prolonged course. The six-month delay in the decline of CDAD after virtual withdrawal of cephalosporins may reflect a slowly diminishing environmental reservoir.

Anti-Bacterial Agents↗

The prevalence of silent kidney stones--an ultrasonographic screening study.

OBJECTIVE: Silent and not yet discovered stones of the upper urinary tract are potentially dangerous, since in due course they may cause infection, obstruction and renal damage. The aim of this study was to determine the prevalence of such silent kidney stones in a representative Pakistani population of Karachi. SUBJECTS AND METHODS: We studied 201 consecutive subjects at our hospital who underwent additional kidney screening whilst undergoing abdominal ultrasound. All these subjects did not have a history or symptoms of urolithiasis. RESULT: We found silent kidney stones in 3% of subjects. All stone bearers were males. Most stones were in the left kidney. Notably, multiple stones and stones of a considerable size went unnoticed. CONCLUSION: In addition to the usual figures of incidence and prevalence of stone disease drawn from patient data, there is a prevalence of 3% silent stones that may only be discovered incidentally or by screening. This is true for a "'stone country" like Pakistan. Figures for other regions have yet to be determined. Due to socioeconomic reasons, we believe that a general kidney screening for urolithiasis is, however, not indicated, at least in our country.

Adolescent↗

A case report of post-traumatic facial reconstruction in the West Indies.

The radial forearm free flap is one of the most commonly used free flaps in reconstructive surgery. It is a recognized option for facial reconstruction internationally, but, to our knowledge, it has not been widely used in the Caribbean. We present a patient who posed a difficult reconstructive problem, for which the radial forearm free flap was the ideal solution, utilizing the flap's features of a long length of pedicle, large area of coverage, minimal tissue bulk, and options for further cosmetic revision.

Adolescent↗

Cerebral involvement in benign tertian malaria.

Although Plasmodium vivax usually causes benign uncomplicated malaria, it can occasionally result in severe disease with life-threatening, end-organ involvement generally seen with falciparum malaria. We report a case of cerebral malaria caused by P. vivax and review the literature on this subject.

Electrophoresis, Agar Gel↗

Combined orthogeriatric care in the management of hip fractures: a prospective study.

AIMS: To evaluate the efficacy of combined care between orthopaedic surgeons and geriatricians in the management of patients with fractured necks of femur. PATIENTS AND METHODS: A prospective study of the admissions to a district general hospital with hip fractures was carried out over a 5-year period. In the years 1992-1994, medical problems in this patient group were managed by a consultation-only service. At the end of 1994, a consultant geriatrician was appointed to manage these patients jointly with the orthopaedic surgeons, and the study was then carried through until the end of 1996. Information about the patients from admission to discharge or death was gathered prospectively using a proforma for the 3 years prior to orthogeriatric care, and the 2 years after. Main outcome measures were mortality, length of stay and discharge destination. These were compared for the two periods--pre- and post-orthogeriatric care. RESULTS: No significant differences were noted in mortality, length of stay or discharge destination. CONCLUSIONS: Combined orthogeriatric care according to our model did not have an impact on our chosen outcome measures.

Aged↗

Optical coherent reflectometry: a new technique to guide invasive procedures.

The success rate of percutaneous transluminal coronary angioplasty for chronic total arterial occlusions is still unsatisfactory. Inability to cross the lesion with a guidewire is a major cause of failure. Optical coherent reflectometry (OCR) is a new method of using laser light to measure the depth of tissue from the end of an optic fiber. This study tests whether an OCR prototype guidewire provides a guidance system that might be useful to assist reopening chronic total arterial occlusions. An OCR fiber optic within a 0.014" hypotube was developed using the interference pattern of two reflected light beams (wave length 1,300 nm). To determine if OCR can distinguish different tissue types, plaques of human lower extremity arterial segments were visually divided into three types (calcified, white, or yellow). The slope of the initial reflectance of the OCR curve was calculated and compared between the three groups. In six other arteries, the OCR wire was advanced longitudinally through occluded human artery segments in vitro. Guidewire position was determined by OCR and compared to the position of the guidewire tip observed simultaneously by intravascular ultrasound (IVUS) imaging. In 16 arterial surface segments, calcified plaques had a significantly steeper slope than white or yellow plaques (-227.2 +/- 82.2; -81.5 +/- 12.9; -103.6 +/- 19.6 dB/mm; P < 0.01). For the determination of the guidewire position, IVUS and OCR corresponded correctly in 82% of 28 measurements. Sensitivity and specificity of OCR for detection of plaque versus the media/adventitia boundary were 79% and 89%, respectively (P < 0.001). OCR can distinguish calcified from noncalcified plaque and may distinguish plaque from the media/adventitia boundary. This technology may be useful as a means to help navigate a guidewire safely through an occluded artery.

Arterial Occlusive Diseases↗

Leber's congenital amaurosis with anterior keratoconus in Pakistani families is caused by the Trp278X mutation in the AIPL1 gene on 17p.

BACKGROUND: Leber's congenital amaurosis (LCA) represents the earliest and severest form of retinal dystrophy leading to congenital blindness. A total of 20% of children attending blind schools have this disease. LCA has a multigenic basis and is proving central to our understanding of the development of the retina. We describe the clinical and molecular genetic features of four inbred pedigrees from neighbouring remote villages in northern Pakistan, in which some of the affected members have concurrent keratoconus. METHODS: History-taking and physical and eye examinations were performed in the field. Venipuncture, DNA extraction, studies of linkage to known LCA genes, automated sequencing and polymorphism analyses for haplotype assessments were done. RESULTS: We examined 12 affected and 15 unaffected family members. By history, there were an additional nine blind people in the four pedigrees. In each pedigree a consanguineous marriage was evident. We found a homozygous nonsense mutation in the AIPL1 gene, which replaces a tryptophan with a stop codon (Trp278X). The phenotype is severe and variable, despite the common molecular genetic etiology in each family. Affected patients had hand motion to no light perception vision and fundus findings ranging from maculopathy to diffuse pigmentary retinopathy. Three affected members had definite keratoconus, and two were suspects based on mild cone formation in the cornea of at least one eye. INTERPRETATION: We have identified four Pakistani families with a severe form of LCA that is associated with severe keratoconus in some affected members. The molecular etiology in all four families is a homozygous nonsense mutation, Trp278X, in the photoreceptor-pineal gene AIPL1. To our knowledge, this is one of the first phenotype-genotype correlations of AIPL1-associated LCA.

Adaptor Proteins, Signal Transducing↗

Lasers in plastic surgery.

The laser is a relatively new tool in many branches of medicine. In particular, in the field of plastic surgery, lasers have found numerous applications. Laser light is produced by the stimulated emission of photons from the lasing medium. Lasers may be classified according to the lasing medium employed, the wavelength of the emitted light and the pulse duration. One of the main uses of lasers is in the treatment of vascular lesions such as port wine stain (PWS). The 585 nm flashlamp pumped pulsed dye laser (FPPDL) is particularly effective in this role. The principle of selective photothermolysis has allowed highly specific targeting of different tissue components. Newer lasers have been developed to treat pigmented lesions as well as primary and metastatic cutaneous malignancies. In cosmetic surgery, lasers have been developed for skin resurfacing and removal of wrinkles, tattoos and unwanted hair. There has been recent interest in the use of lasers to promote wound healing. Laser therapy is not without complications and the safety of both patient and operator must remain paramount. The future is likely to hold greater advances in this rapidly developing field.

Humans↗

Latropathic injuries of peripheral nerves.

This is a retrospective study of 612 cases of iatropathic injury to peripheral nerves seen in one tertiary referral unit between 1991 and 1998. A total of 291 patients was subsequently operated on to explore the nerve lesion. The most common presenting symptom was pain, which often masked underlying loss of function. The delay in diagnosis was up to 40 months. The findings at operation were analysed according to the type of nerve damaged, the nature of the injury and the referring specialty. Some of the more common causal operations and procedures are discussed. Preventive measures are listed, and early diagnosis and treatment are recommended.

Adult↗

Consent to surgery in a high risk specialty: a prospective audit.

A prospective audit was performed to assess how well patients were being consented for neurosurgery. Sixty patients with various neurosurgical conditions were included in the study. Audit was performed firstly by means of a questionnaire to examine the type of information given to patients, and their understanding of such information. Secondly, the patient's medical notes were reviewed to analyse any written evidence by the consenting doctor for the consenting procedure. 100% of the patients felt that they had been informed satisfactorily about the nature of their condition and the nature of the operation. 92% understood the specific risks of their proposed operation. However, only 25% were informed about the general risks of surgery and anaesthesia. Only 33% felt that they were informed fully about alternative treatment options. 97% of the patients felt that they had reached an informed decision regarding surgery. 67% of the case notes contained information on the nature and specific risks of the operation, while information on general risks of surgery and anaesthesia was documented in only 17% of the case notes. 33% of the case notes contained no information for the consenting procedure. Our audit showed that the patients had a good understanding of the nature and aim of the operation and the specific risks. Areas that require improvement are explaining the general risks of surgery and alternative treatment. For the consenting doctor, there should be more documentation in the notes, and there should be mention of the doctor's satisfaction that the patient was deemed to be competent and had made an informed decision.

Adult↗

A new Alamar Blue viability assay to rapidly quantify oligodendrocyte death.

We developed a rapid fluorometric viability assay for primary cultures of OL precursors (preOLs) or mature OLs that utilized the oxidation/reduction indicator dye Alamar Blue (AB). PreOLs had a lower rate of AB reduction than did mature OLs (0.02 +/- 0.01 units/min per cell versus 0.07 +/- 0.01). The assay was tested under two conditions toxic to preOLs: oxidative stress induced by glutathione depletion or kainate excitotoxicity. When glutathione was depleted by a 24-h exposure to cystine-depleted medium, the EC50 values for the dependence upon cystine for survival did not differ significantly when determined by AB reduction (2 +/- 2 microM), by the trypan blue exclusion method (3 +/- 3 microM) or by MTT histochemistry (1 +/- 0.4 microM). Quantification of preOL viability with AB was unaffected by the presence of free radical scavengers (alpha-tocopherol or idebenone) or the antioxidant enzymes Cu,Zn-superoxide dismutase and catalase. There was no difference in preOL viability as determined by AB or MTT after a 24-h exposure to kainate at concentrations up to 1 mM. AB offers a rapid objective measure of OL viability in primary culture and is a valid means to quantify OL death.

Animals↗

Acute encephalopathy and intractable seizures in a 10-year-old boy.

We report a 10-year-old child with Robinow's syndrome who had a 2-week history of headaches and dizziness. On the day of admission, he developed a focal onset seizure with rapid secondary generalization. The seizures were intractable despite adequate doses of benzodiazepine, phenytoin, and phenobarbital, requiring a pentobarbital drip. Continuous electroencephalogram (EEG) monitoring showed persistence of the epileptiform discharges for 13 days. Cerebrospinal fluid and brain biopsy studies were unrevealing. Mycoplasma pneumonia titers showed elevation of both immunoglobulins G and M that doubled during the tenth hospital day. High-dose methylprednisolone was begun, and within 12 hours of initiation the patient sat up and began to follow commands appropriately. The overall EEG background markedly improved. Central nervous system Mycoplasma pneumoniae infection should be suspected in patients with an encephalopathy of unclear etiology.

Acute Disease↗

Chromosome 11q13 and atopic asthma.

Asthma is a complex syndrome in which bronchial inflammation and smooth muscle hyperactivity lead to labile airflow obstruction. The commonest form of asthma is that due to atopy, which is an immune disorder where production of IgE to inhaled antigens leads to bronchial mucosal inflammation. The ultimate origins of asthma are interactive environmental and genetic factors. The genetics is acknowledged to be heterogeneous, and one chromosomal region of interest and controversy has been 11q13. To clarify the nature of the chromosome 11q13 effect in atopy and asthma, we conducted a genetic association study in subjects with marked atopic asthma and matched controls, which incorporated the study of 13 genetic variants over a distance of 10-12 cM and which took account of detailed immune and clinical phenotyping. Association with high IgE levels was limited to the interval flanked by D11S1335 and CD20 in a 0.8-Mb interval and was greatest for variants of Fc epsilonRIbeta and HTm4; these variants also associated with asthma (recurrent wheeze with labile airflow obstruction and need for regular inhaler treatment). At the more telomeric marker, D11S480, variants associated with asthma, but not with high IgE levels. The data might support the possibility of multiple loci relevant to atopic asthma on chromosome 11q13.

Alleles↗

Free-radical-generated F2-isoprostane stimulates cell proliferation and endothelin-1 expression on endothelial cells.

BACKGROUND: Free-radical-generated F2-isoprostane stimulates DNA synthesis and endothelin-1 (ET-1) expression on endothelial cells. 8-Iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a member of the recently discovered family of prostanoids, the F2-isoprostanes, produced in vivo by cyclooxygenase-independent, free-radical-catalyzed lipid peroxidation. The goal of our study is to establish the effect of isoprostane on ET-1 production by endothelial cells, as well to determine the receptors responsible for these effects. METHODS: The proliferative effect of isoprostanes was measured as an increase of viable cell number and [3H]-thymidine uptake. ET-1 gene expression and protein synthesis were determined by Northern blot and radioimmunoassay, respectively. We also determined inositol 1,4,5-trisphosphate synthesis. Thromboxane A2 (TXA2) receptor antagonist SQ29,548 was used to establish the role of TXA2 receptor in isoprostane effect, as well as to determine the type of receptors involved in these effects. RESULTS: Our results show that physiological concentrations of 8-iso-PGF2alpha stimulated cell proliferation, DNA synthesis, and ET-1 mRNA and protein expression in bovine aortic endothelial cells (BAECs). The proliferative effect was partially abolished by treatment with anti-endothelin antibody. 8-Iso-PGF2alpha also increased inositol 1, 4,5-trisphosphate formation in these cells. These effects were partially inhibited by SQ29,548. In competitive binding assays, two binding sites were recognized on BAECs with dissociation constants (Kd) and binding site densities at equilibrium similar to those previously described in smooth muscle cells and likely represent [3H]-8-iso-PGF2alpha binding to its own receptor (high-affinity binding site) and cross-recognition of the TXA2 receptor (low-affinity binding site). CONCLUSION: These studies expand the potential scope of the pathophysiologic significance of F2-isoprostanes, released during oxidant injury, to include alteration of endothelial cell biology.

Animals↗

Anterior jugular venous aneurysm.

An anterior jugular venous aneurysm in a 4-year-old boy is described. Noninvasive radiology confirmed the diagnosis and excluded any deeper cervical venous malformation. Surgical excision was uncomplicated. Whilst the internal jugular vein is the commonest site of a venous aneurysm, recognition that the anterior jugular vein can be affected in isolation may help to avoid diagnostic confusion. A unifying concept of pathogenesis is suggested.

Aneurysm↗