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Biomedical subjects

I H Khan

Publications and source records attributed to I H Khan.

At least 19 recordsLinked to original sources
PubMed2000

Can we improve early mortality in patients receiving renal replacement therapy?

BACKGROUND: Approximately one in eight patients with end-stage renal disease (ESRD) die within the first three months of starting renal replacement therapy (RRT). We investigated which factors might improve this early mortality. METHODS: We performed a prospective nationwide study of all patients commencing RRT for ESRD in Scotland over one year. Patients were classified according to how they presented to start RRT, their burden of comorbid diseases, access prepared for dialysis, and duration of care by a nephrologist prior to commencing RRT. Those factors most strongly associated with death within 90 days of commencing treatment were determined by logistic regression analysis. RESULTS: Patients with an acute unexpected element to their presentation for RRT had early mortality rates between 6.0 and 8.9 times greater than those who commenced RRT electively after a period of care from a nephrologist. Patients in high and medium comorbidity risk groups had early mortality rates of 4.7 and 2.2 times greater than those in the low-risk group. Low serum albumin had a significant association with early death. Patients who progressed steadily to ESRD, who had a planned start to dialysis, and who had mature access were 3.6 times more likely to survive beyond three months than those with no access; they were, however, also younger with less comorbidity. CONCLUSIONS: The factors principally associated with early mortality are nonelective presentation for RRT, comorbid illness, and low serum albumin. Patients cared for by a nephrologist before requiring RRT who have mature access have better short-term survival than those without access. They are also younger with less comorbidity. It may be possible to improve short-term survival in this "unplanned" group if referred early to facilitate reducing cardiovascular risk factors and preparation for RRT.

Adolescent↗
PubMed1999

Glycoside primers of Psittacanthus cucullaris.

Bioassay-directed chromatographic separation of the ethyl acetate extract of the whole plant of Psittacanthus cucullaris afforded a new phenolic xyloside, ellagic acid-4-O-beta-xyloside-3,3', 4'-trimethyl ether (1) together with four known compounds, ellagic acid-4-O-beta-xyloside-3,3'-dimethyl ether (2), gallic acid, beta-sitosterol, and beta-sitosterol beta-D-glucoside. The structure of the new compound was determined by spectroscopic methods. Like other beta-D-xylosides, compounds 1 and 2 stimulated the formation of glycosaminoglycan chains when fed to the cultured Chinese hamster ovary cells.

Animals↗
PubMed1999

Equity of renal replacement therapy utilization: a prospective population-based study.

This 1-year prospective survey assessed the incidence and characteristics of all patients starting renal replacement therapy (RRT) for end-stage renal disease in Scotland, and whether there is equity of utilization of RRT in terms of age, domicile and social circumstance. In the year studied, 104 patients per million population (533 patients) started RRT (390 per million population aged 65-75). In 23.5% the cause of ESRD could not be determined. Diabetes was the single most frequently identified cause (16%). The requirement for RRT rose with age, but over the country as a whole, patients aged over 75 years were under-represented. The majority of health boards provided RRT at a rate within 20% of the national rate. There was no difference in the median age at starting RRT between health boards. The spectrum of social deprivation of patients starting RRT was the same as that of the general population. There was no evidence that social deprivation influences acceptance on to the RRT program, although the relationship between ESRD and deprivation is complex. The utilization of RRT exceeded the minimum rate recommended by the Renal Association, although there was fluctuation between health board areas. The national requirement for resources to provide RRT is likely to rise further to care for an increasingly elderly population.

Adolescent↗
PubMed1999

A national survey of thoracic surgical practice in the UK.

We conducted a survey of thoracic surgery in the UK today. Questionnaires were sent to 75 cardiothoracic surgeons, known to perform thoracic surgery regularly; we had a 100% response. The commonest preoperative investigations for carcinoma of the oesophagus were serum alkaline phosphatase (90%), GGT (69%), contrast swallow (80%), ultrasound of abdomen (71%) and CT scan of chest and abdomen (60%). After oesophagectomy, 84% of the surgeons inserted nasogastric tubes and 31% sent their patients to the intensive care unit. Oral fluids were started on days 3-5 in 81% of cases, and 58% of the surgeons requested a postoperative contrast swallow, usually between the seventh and tenth postoperative days, after oral fluids had been started. Most of the surgeons nearly always used staplers for a given procedure or else completely avoided them for that part of the operation. The commonest use of staplers was for bronchial closure in pneumonectomy (67%) and lobectomy (48%) and in constructing an oesophageal anastomosis (25%). Twenty per cent of the surgeons did not insert a chest drain after pneumonectomy, while 65% observed the protocol of chest drain insertion with short intermittent unclamping, usually every hour, followed by removal of the drain, usually the next morning. Thoracic surgeons vary widely in their surgical practices. In a well structured training programme, trainees should rotate between several units so they are exposed to different techniques and ideas and acquire a broad based training.

Chest Tubes↗
PubMed1998

Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.

Adolescent↗
PubMed1998

Role of the SH3-ligand domain of simian immunodeficiency virus Nef in interaction with Nef-associated kinase and simian AIDS in rhesus macaques.

The nef gene of the human and simian immunodeficiency viruses (HIV and SIV) is dispensable for viral replication in T-cell lines; however, it is essential for high virus loads and progression to simian AIDS (SAIDS) in SIV-infected adult rhesus macaques. Nef proteins from HIV type 1 (HIV-1), HIV-2, and SIV contain a proline-Xaa-Xaa-proline (PxxP) motif. The region of Nef with this motif is similar to the Src homology region 3 (SH3) ligand domain found in many cell signaling proteins. In virus-infected lymphoid cells, Nef interacts with a cellular serine/threonine kinase, designated Nef-associated kinase (NAK). In this study, analysis of viral clones containing point mutations in the nef gene of the pathogenic clone SIVmac239 revealed that several strictly conserved residues in the PxxP region were essential for Nef-NAK interaction. The results of this analysis of Nef mutations in in vitro kinase assays indicated that the PxxP region in SIV Nef was strikingly similar to the consensus sequence for SH3 ligand domains possessing the minus orientation. To test the significance of the PxxP motif of Nef for viral pathogenesis, each proline was mutated to an alanine to produce the viral clone SIVmac239-P104A/P107A. This clone, expressing Nef that does not associate with NAK, was inoculated into seven juvenile rhesus macaques. In vitro kinase assays were performed on virus recovered from each animal; the ability of Nef to associate with NAK was restored in five of these animals as early as 8 weeks after infection. Analysis of nef genes from these viruses revealed patterns of genotypic reversion in the mutated PxxP motif. These revertant genotypes, which included a second-site suppressor mutation, restored the ability of Nef to interact with NAK. Additionally, the proportion of revertant viruses increased progressively during the course of infection in these animals, and two of these animals developed fatal SAIDS. Taken together, these results demonstrated that in vivo selection for the ability of SIV Nef to associate with NAK was correlated with the induction of SAIDS. Accordingly, these studies implicate a role for the conserved SH3 ligand domain for Nef function in virally induced immunodeficiency.

Animals↗
PubMed1997

Scleroderma, D-penicillamine treatment, and progressive renal failure associated with positive antimyeloperoxidase antineutrophil cytoplasmic antibodies.

Progressive renal failure in patients with scleroderma is a sinister development that is usually attributed to impaired renal blood flow. In some exceptional cases, the underlying pathology is a crescentic glomerulonephritis, which has been associated with positive antineutrophil cytoplasmic antibodies, and in particular antimyeloperoxidase antibodies. The prognosis in such cases has been very poor. We report such a patient whose renal function has improved and stabilized on immunosuppressive therapy.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Characterization of flagella genes of Agrobacterium tumefaciens, and the effect of a bald strain on virulence.

Agrobacterium tumefaciens produces flagella that are arranged circumthecally near one end of the bacilliform cell. The flagella are required for motility to facilitate reaching the root surface, and possibly aid in orientating the bacterial cells at various sites for infection. We have identified three flagella genes designated flaA, flaB, and flaC. Mutations in flaA, flaB and flaC result in abberant swimming behaviour. Electron microscopic examination of these mutants revealed the defective flagella. A non-motile, bald mutant strain was generated by deleting all three fla genes. Nucleotide sequencing of flaA, flaB, and flaC showed that they have a potential coding capacity for polypeptides of 307, 321, and 314 amino acid residues, respectively. The predicted amino acid sequences of the A. tumefaciens FlaA and FlaB proteins are similar (66% average identity) to the FlaA and FlaB proteins encoded by flaA and flaB genes, respectively, in Rhizobium meliloti. There was no counterpart FlaC protein reported in R. meliloti, but the A. tumefaciens FlaC is similar in amino acid sequence to the R. meliloti FlaA (59.8% identity) and FlaB (66.7% identity). Distinct from FlaA and FlaB of R. meliloti is the absence of histidine and cysteine residues and their shorter length (by 88 amino acid residues fewer than FlaA and FlaB of R. meliloti). The transcriptional start sites of each fla gene determined by primer extension revealed consensus-sequence boxes representing potential binding sites for sigma 28 RNA polymerase (RNAP) upstream of the transcriptional start of each fla gene. Besides the potential sigma 28-binding site upstream of flaC, also present are additional putative conserved sequences, GC at -11 and GG at -21 from the transcriptional start, that resemble potential binding motifs for sigma 54. Because the sigma 54 promoter is associated with genes regulated by physiological changes in various bacteria, the flaC gene might be similarly regulated in response to A. tumefaciens responding to host plant stimuli. Virulence studies showed that the bald strain was consistently reduced in virulence below that of the parental wild-type strain by at least 38%. The difference is statistically significant and suggests that the flagella may play a role in facilitating virulence.

Agrobacterium tumefaciens↗
PubMed1997

Acute renal failure: factors influencing nephrology referral and outcome.

We investigated the incidence, factors affecting referral and outcome of acute renal failure (ARF), in an unselected (predominantly Caucasian) population in the Grampian region of Scotland served by a single renal unit. Case-notes were examined for all patients with a serum creatinine > or = 300 mumol/l. ARF (311 patients) was defined as a temporary rise in serum creatinine > or = 300 mumol/l, or, if the patient died during the acute illness, clinical features indicating acute deterioration of previously normal renal function. Advanced ARF at presentation (51 of the 311 with ARF) was defined as a first recorded serum creatinine > or = 500 mumol/l. Patients were classified into low-, medium-, and high-risk groups according to presence of comorbidity and age. The annual incidence of ARF was 620/million population (pmp), that of advanced ARF 102 pmp. The age-related incidence of ARF ranged from 30 pmp in the age group (0-19 years) to 4266 pmp in the age group > 80 years. Overall, 22% were referred to a nephrologist (34% after excluding those with advanced cancer and age > 80 years). Referral of patients decreased from 100% in the age group 0-19 to 5% in those > 80 years. Referrals in the low-, medium- and high-risk groups were 75%, 30% and 14%, respectively. Patient survival at 2 years was 80%, 42% and 19% for low-, medium-, and high-risk groups, respectively (86%, 44% and 32% for referred patients). Referral and outcome in patients with ARF were significantly influenced by age and presence of comorbidity at presentation.

Acute Kidney Injury↗
PubMed1997

The effect of exercise training on physical fitness and plasma lipids in young Chinese men and women.

BACKGROUND: The mortality from coronary heart disease (CHD) has been steadily increasing in many parts of the world. Measures to reduce the incidence of CHD were initially addressed mainly to middle aged and elderly population groups, but for effective prevention of CHD, measures addressed to younger age groups are also necessary. Moreover, differences between male and female plasma lipid changes after exercise training are not known exactly. METHODS: The concentrations of plasma lipids, before and after regular physical exercise training for 12 weeks, were analyzed in 25 male and 25 female medical students of the same age group. Physical fitness was evaluated by the measurement of maximum oxygen uptake. RESULTS: Results indicated that plasma tri-glyceride, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol differences between the before-and-after exercise were significant (p < 0.05) in males while the differences of plasma total cholesterol were found to be insignificant. In females there were no significant changes in the plasma lipids levels. In both males and females, the marked increase in maximal O2 uptake after exercise training indicated an improvement in physical fitness. CONCLUSIONS: This study concludes that a short-term exercise program can improve plasma lipid and lipoprotein patterns more in males than in females. It also suggests that daily physical exercise may be an important prevention for cardiovascular diseases in later life, so it is essential to establish a life style with optimum nutrition and physical activity in both the young and in adults of all ages.

Adult↗
PubMed1997

Monthly measurements of intraocular pressure in normal, ocular hypertensive, and glaucoma male subjects of same age group.

BACKGROUND: Recently it has been shown that environmental conditions have a significant influence on intraocular pressure (IOP). Due to differences in inherent constitution, diet and environmental conditions, there is a clear need for well collected IOP data in different countries and ethnic groups. The seasonal variation of IOP has never been described in Pakistani subjects. METHODS: IOP was measured each month over the course of 12 months with the Goldmann applanation tonometer in normal, ocular hypertensive, and glaucoma male subjects. RESULTS: In all groups, the average intraocular pressures in the winter months were highest, while lowest in summer months. The intraocular pressures of spring and autumn months were nearly the same. The intraocular pressure levels in these seasons were between the IOP levels in summer and winter seasons. The difference between highest and lowest IOP was 1.4 +/- 0.2, 3.1 +/- 1.4, and 2.3 +/- 1.1 mmHg, in normal, ocular hypertensive, and glaucoma subjects, respectively. The ups and downs of intraocular pressure were greater in the ocular hypertensive subjects than in the glaucoma patients. CONCLUSIONS: This study confirms that season influences IOP, and concludes that seasonal influence is highest in ocular hypertensive than in normal and glaucoma subjects. As compared to other nations, effect of seasons on IOP seems to be somewhat less pronounced in Pakistan.

Glaucoma↗
PubMed1996

Activation of PAK by HIV and SIV Nef: importance for AIDS in rhesus macaques.

BACKGROUND: The primate lentiviruses, human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV), encode a conserved accessory gene product, Nef. In vivo, Nef is important for the maintenance of high virus loads and progression to AIDS in SIV-infected adult rhesus macaques. In tissue culture cells expressing Nef, this viral protein interacts with a cellular serine kinase, designated Nef-associated kinase. RESULTS: This study identifies the Nef-associated kinase as a member of the p21-activated kinase (PAK) family of kinases and investigates the role of this Nef-associated kinase in vivo. Mutants of Nef that do not associate with the cellular kinase are unable to activate the PAK-related kinase in infected cells. To determine the role of cellular kinase association in viral pathogenesis, macaques were infected with SIV containing point-mutations in Nef that block PAK activation. Virus recovered at early time points after inoculation with mutant virus was found to have reverted to prototype Nef function and sequence. Reversion of the kinase-negative mutant to a kinase-positive genotype in macaques infected with the mutant virus preceded the induction of high virus loads and disease progression. CONCLUSIONS: Nef associates with and activates a PAK-related kinase in lymphocytes infected in vitro. Moreover, the Nef-mediated activation of a PAK-related kinase correlates with the induction of high virus loads and the development of AIDS in the infected host. These findings reveal that there is a strong selective pressure in vivo for the interaction between Nef and the PAK-related kinase.

Acquired Immunodeficiency Syndrome↗