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Biomedical subjects

M A Khan

Publications and source records attributed to M A Khan.

At least 37 records · Page 2Linked to original sources

Stromal-epithelial measurements of prostate cancer in native Japanese and Japanese-American men.

We measured the histologic stromal and epithelial tissue components of the benign (normal) and malignant tissue compartments of Japanese-Americans (J-A) and native Japanese (NJ) men living in Japan. The patient cohort included 25 NJ men undergoing radical prostatectomy (RP) in Nagoya, Japan and 25 J-A (second or third generation US born). We conducted tissue image quantitation (in-house image software) of the stromal and epithelial compartments in malignant and adjacent normal tissue areas from a tissue microarray (TMA) selected from radical prostatectomy (RP) blocks. Stromal-epithelial (S-E) areas were determined using immunohistochemical stains for CAM-5.2 epithelial cytokeratin marker and the Masson trichrome stain to measure the stroma component. We observed differences in the volumes of normal and cancer epithelium and stroma within both the J-A and NJ study populations (P<0.01). Only the individual average cancer epithelium (CE) volume (JA=24.1 vs NJ=29.9) differed significantly between the NJ and J-A study populations (P=0.03). Consequently, the S-E ratio in NJ group was significantly different from that of J-A population (P=0.05). The decrease in S-E ratio noted in the malignant tissues of NJ prostate tissue may provide a biological marker for differentiation of the two groups and suggests a need for further investigations into the molecular basis for these histologic differences.

Aged↗

Inflammatory antigens of Brugia malayi and their effect on rodent host Mastomys coucha.

The study was aimed at identifying pro- and anti-inflammatory cytokine releasing potential of Brugia malayi adult worm fractions and their role in filarial infection and pathogenesis. THP-1 cells were incubated with soluble somatic Brugia malayi adult worm extract (BmAS) and its Sephadex G-200 fractions BmAFI, BmAFII and BmAFIII and the effect of the fractions on parasitological, immunological and lymph node parameters was assessed in Mastomys coucha. BmAFII stimulated the pro-inflammatory TNF-alpha, IL-1beta and IL-6 release; IL-10 release was insignificant. Sensitization of animals with BmAFII and subsequent intraperitoneal implantation of worms enhanced CMI response. BmAFII also increased lymph node weight and cellularity, stimulated lymph node mast cells and eliminated intraperitoneally instilled worms. BmAFI stimulated several folds more release of IL-10, whereas TNF-alpha release was negligible. Sensitization with BmAFI elicited low CMI responses, moderately stimulated mast cells and facilitated survival of implanted adult parasites. Fifty percent of naive animals exposed to BmAFI showed oedematous lymph nodes and increased node weight. NCP-bound molecules corresponding to BmAFI and II showed cytokine-stimulating potential in vitro. It is concluded that BmAFII is protective and stimulates pro-inflammatory cytokines, whereas BmAFI facilitates parasite survival and stimulates IL-10.

Animals↗

How to diagnose axial spondyloarthritis early.

BACKGROUND: Chronic low back pain (LBP), the leading symptom of ankylosing spondylitis (AS) and undifferentiated axial spondyloarthritis (SpA), precedes the development of radiographic sacroiliitis, sometimes by many years. OBJECTIVE: To assign disease probabilities and to develop an algorithm to help in the early diagnosis of axial SpA. METHODS: Axial SpA comprises AS and undifferentiated SpA with predominant axial involvement. Clinical features include inflammatory back pain (IBP), alternating buttock pain, enthesitis, arthritis, dactylitis, acute anterior uveitis, a positive family history, psoriasis, inflammatory bowel disease, and good response to NSAIDs. Associated laboratory findings include raised acute phase reactions, HLA-B27 association, and abnormalities on skeletal imaging. Sensitivities, specificities, and likelihood ratios (LRs) of these parameters were determined from published studies. A 5% prevalence of axial SpA among patients with chronic LBP was used. The probability of the presence of axial SpA, depending on the presence or absence of the above clinical features of SpA, was determined. A probability of > or = 90% was used to make a diagnosis of axial SpA. RESULTS: The presence of inflammatory back pain features increased the probability of axial SpA from the background 5% prevalence to 14%. The presence of 2-3 SpA features was necessary to increase the probability of axial SpA to 90%. The highest LRs were obtained for HLA-B27 and MRI. Diagnostic algorithms to be used in daily practice were suggested. CONCLUSIONS: This approach can help clinicians to diagnose with a high degree of confidence axial SpA at an early stage in patients with IBP who lack radiographic sacroiliitis.

Axis, Cervical Vertebra↗

Status of rheumatic heart disease in rural Pakistan.

OBJECTIVES: To determine the community based prevalence of rheumatic heart disease (RHD) in the rural population of the district of Rahim Yaar Khan in Pakistan. SUBJECTS AND METHODS: A representative sample of the rural population of Rahim Yaar Khan district was selected. RHD was screened for by physical examination and the diagnosis was confirmed with echocardiographic Doppler studies. Sociodemographic data on each screened person were collected. RESULTS: 54 cases of RHD were found among the 9430 people screened (prevalence of 5.7 in 1000, 95% confidence interval 4.2 to 7.2). Females were significantly more likely to be affected. There was no significant relation with other factors studied (education, crowding, and socioeconomic status). Less than 20% of those found to have RHD were aware of their diagnosis before participation in this study and only three affected people (8%) were taking rheumatic prophylaxis. CONCLUSIONS: There is a high prevalence of RHD among the rural population of Pakistan. The prevalence has not declined over the past three decades. Nearly all people with RHD, including most of those who know their diagnosis, do not receive the benefit of potentially life saving secondary prevention measures.

Adolescent↗

Responses of Mastomys coucha, that have been infected with Brugia malayi and treated with diethylcarbamazine or albendazole, to re-exposure to infection.

The responses of Mastomys coucha to re-exposure to infection with homologous infective larvae (L(3)) of Brugia malayi were investigated, after initial infections with the nematode had been treated subcutaneously for 5 days with diethylcarbamazine (DEC; 150 mg citrate/kg. day) or albendazole (ALB; 50 mg/kg. day). The parasite burdens, serum concentrations of IgG reacting with a soluble somatic extract of adult B. malayi (BmAS), and cytokine and lymphocyte-proliferative responses to filarial antigen (BmAS) or mitogen (concanavilin A or lipopolysaccharide) were studied. The results demonstrated, for the first time, that re-infection with L(3) was only successful in the DEC-treated animals, not the ALB-treated ones. When the ALB-treated animals were re-exposed, interferon-gamma production decreased, lymphocyte-proliferative responses either remained the same (with concanavilin A) or decreased (with BmAS), and concentrations of specific IgG decreased. When the DEC-treated animals were re-exposed, microfilaraemias re-appeared and, although production of interferon-gamma decreased, there were no detectable lymphocyte proliferative responses, and concentrations of specific IgG remained unchanged. Taken together, the results indicate that, at least in the M. coucha model of human filariasis, ALB but not DEC treatment may help to prevent the development of re-infections.

Albendazole↗

Down-regulation of nitric oxide synthase in the diabetic rabbit kidney: potential relevance to the early pathogenesis of diabetic nephropathy.

OBJECTIVES: Nephropathy is a well-recognised complication of diabetes mellitus (DM). The aim of this study was to investigate the effect of DM on the density and distribution of nitric oxide (NO) synthase (NOS) in the rabbit kidney. Quantification of the NOS radioligand on slide-mounted sections was compared with the nitroblue tetrazolium reaction, where the intensity of the reaction varies with the nicotinamide adenine dinucleotide diaphorase (NADPH-d) activity of NOS. MATERIALS AND METHODS: DM was induced with alloxan in six New Zealand White (NZW) rabbits. Plasma creatinine, urea and electrolytes were monitored at monthly intervals. The kidneys were removed following 6 months of DM. Transverse serial sections were cut and low-resolution autoradiography was performed using a radioligand for NOS ([(3)H]-NOARG). Histochemical localisation of NADPH-d activity was also performed. Densitometric analysis was performed on the autoradiographs and the results compared with those obtained from six age-matched control rabbits. RESULTS: There was a significant (p < 0.01) rise in plasma creatinine levels in the diabetic rabbits, although the mean values remained within the reference range. There was a significant (p < 0.0001) down-regulation of NOS binding sites in both the cortex and medulla of the DM kidney when compared with the controls. A similar decrease in NADPH-d activity was seen in the diabetic renal cortex and medulla. In addition, NADPH-d activity also appeared to be reduced in the diabetic glomeruli when compared with controls. CONCLUSIONS: NOS binding sites and NADPH-d activity are significantly decreased in the DM renal cortex and medulla. These changes are associated with a mild deterioration in renal function and may be an early event that could subsequently play a role in the progression of DM nephropathy. Manipulating the NO pathway during the early stages of DM nephropathy may be beneficial.

Animals↗

Emerging bacterial resistance patterns in febrile neutropenic patients: experience at a tertiary care hospital in Pakistan.

OBJECTIVE: To look at the clinical presentations, spectrum and site of isolation of the organisms, sensitivity patterns of the organisms and the antibiotic prescribing practices for the treatment of febrile neutropenic patients at our hospital. METHODS: The data were collected retrospectively from the records of all neutropenic patients with an absolute neutrophil count (ANC) of less than 500/ml admitted during the period of 3 years from August 1999 to July 2002 at AKUH. RESULTS: Out of the total of 404 patients, 65% had hematological malignancies and around half of them had leukaemia, 86% of the patients presented with fever. A total of 124 bacterial organisms were isolated from 96 patients among which 47% were gram positive and 53% were gram negative organisms; 16.1% of the patients had septicaemia. Coagulase Negative Staphylococci (CoNS) were the most common gram positive and E. coli was the most commonly isolated gram negative organism. Most of the gram positive organisms were isolated from blood (67%). There was emerging resistance to all commonly used antibiotics including imipenem, cloxacillin, vancomycin and amikacin. The average duration of neutropenia was 6.4 days. The mortality rate was 6%. CONCLUSION: There is increasing trend of gram negative organisms developing resistance to commonly used antibiotics. Gram positive bacteria including Enterococcus spp. and CoNS are also showing emerging resistance to vancomycin.

Amikacin↗

"Decoking" of a "coked" zeolite catalyst in a glow discharge.

"Decoking" of a "coked" zeolite catalyst in a glow discharge in oxygen is investigated. The "decoking" process involves reactions of atomic oxygen (O atoms) with "coke" and yields gases such as CO, CO(2) as well as other gaseous products that could be easily pumped out. Three different modes of discharge were investigated including a static mode, a flowing-gas mode, and a periodic-purge mode where the oxygen and other gaseous products of the discharge were replaced by fresh O(2)gas after short but regular intervals of time. In some cases, additional heating was also used to provide base temperatures of the order of 100 degrees C to facilitate penetration of oxygen atoms into the inner layers and cages of the zeolite catalyst. This paper presents some results of spectroscopic analytical techniques used to monitor the atomization of oxygen, oxidation of "coke", and to confirm the process of "decoking". More specifically, radiation emission on the 3 s (5)S- 3p (5)P transitions of O around 777.2-777.5 nm were selected for monitoring the atomization of O(2). On the other hand, X-ray photo-electron spectroscopy (XPS) was used to determine the amount of residual carbon and extent of "decoking". Furthermore, evolution of CO and CO(2) gases as a function of time was systematically monitored in real time. For CO, the 451.1 nm band head belonging to the B(1) Sigma - A(1) Pi bands of the Angstrom system of the CO spectrum was used, while for CO(2), the band head at 353.4 nm belonging to the CO(2)(+) spectrum was used. The rates of evolution of CO and CO(2) were related to the rate of "decoking" of the catalyst. It is noted that in the periodic-purge mode, about 63% of the total yield of CO from a given sample of the catalyst appears in the first 3-min exposure to discharge whereas it takes up to 15 min to remove nearly 94% of the removable carbon under our experimental conditions.

Journal Article↗

Distribution and bioavailability of copper in farm effluent.

Effluent and sludge samples from a number of dairy and piggery units in the North Island of New Zealand were collected and analysed for free ionic-copper (Cu(2+)) and organically-complexed Cu. The bioavailability of sludge-Cu was examined using microbial respiration and plant growth experiments. Microbial respiration was measured at various levels of Cu (0-1000 mg kg(-1)), added as copper sulfate (CuSO(4)) and sludge-Cu, using a Gilson differential respirometer. A glass house experiment was conducted to examine the transformation of Cu in soils and its subsequent uptake by ryegrass pasture. Three Cu sources were used that included fast-release CuSO(4), slow-release copper oxide (CuO) and Cu-enriched sludge. The pasture samples were analysed for Cu concentration. The transformation of Cu in the soil was monitored by analysing the soil samples for various fractions of Cu. The effluent and sludge samples collected from farms which regularly used Cu to treat lameness in dairy cattle and as a growth promoter in swine contained higher concentration of Cu. The total Cu concentration ranged from approximately 0.1 to 1.55 mg l(-1) and from 0.5 to 10.5 mg l(-1) in the piggery and diary effluent, respectively. The corresponding values for the sludge samples were 3.0-526 and 25-105 mg kg(-1). Most of the Cu in both the effluent and solid sludge material was organically complexed. The respiration measurements indicated that sludge-Cu was less toxic to soil microbial activity than CuSO(4). The results from the glass house experiment indicated that increasing the level of Cu applied through fertilisers and sludge increased Cu concentration in plants. At the same rate of application, plants took up less Cu from sludge and CuO than from CuSO(4). There was, however, a greater translocation of Cu from root to shoot at the highest rate of Cu through sludge application. The Cu fractionation study indicated that there was greater accumulation of organic bound Cu in the sludge-treated soil than the fertiliser-treated soil.

Animals↗

Synthesis and antifilarial evaluation of N1,Nn- xylofuranosylated diaminoalkanes.

A series of N(1),N(n)-xylofuranosylated diaminoalkanes (3-9 and 11-18) has been synthesized either by reductive amination of deoxy xylouloses (2a, 2b) with amines followed by one pot reduction with NaBH(4) or NaCNBH(3); or by 1,4-conjugate addition of amines to glycosyl olefinic esters (10a, 10b). The compounds were screened for their interference with filarial worms' glutathione metabolism, a potential target for chemotherapeutic attack. Interestingly, these compounds affected intracellular glutathione, gamma-glutamyl cysteine synthetase, glutathione reductase and glutathione-S-transferase(s) of bovine filarial worms to varying degrees. Some of the compounds though effected the motility and MTT reduction potential of filarial worms Brugia malayi, however, little microfilaricidal and macrofilaricidal were noted with compounds at 50mg/kg oral dose. Compounds 6, 16 and 17 were evaluated also for in vivo activity.

Alkanes↗

Alcohol and drug use in Australian male sex workers: its relationship to the safety outcome of the sex encounter.

This paper describes the self-reporting patterns of alcohol and drug consumption among male sex workers (MSWs) in three Australian cities during commercial sex encounters, and examines to what extent alcohol and drugs are used and whether this is related to the safe/unsafe outcome of the commercial sex encounter. One hundred and eighty-six MSWs from Brisbane, Sydney and Melbourne completed a diary following each commercial sex encounter over a two-week period. MSWs reported 2,087 commercial sex encounters during the study period. Alcohol or drug consumption was reported in 50.5% of the encounters. There were 488 instances of marijuana use reported before or during a commercial sex encounter, 210 instances of volatile inhalants use, 149 instances of heroine use and 151 of other drug use, including benzodiasepines, ecstasy, speed and cocaine. These substances were consumed either alone or combined. Marijuana consumption was associated with the commercial sex encounter occurring at the MSWs' place of residence and consumption of alcohol, marijuana and nitrites with the client's place. The results also reveal that consumption of drugs and alcohol was statistically related to length of the encounter, and that clients obtained through escort agencies or brothels were significantly associated with marijuana, other drug consumption and heroine use. Interestingly, a multivariate analysis indicated that encounters where the MSW consumed marijuana or did not consume any substance were less likely to have an unsafe outcome. The paper argues that it is necessary to identify and target risk groups and behaviours that are usually not included in broad based health education messages.

Adolescent↗

Initiation of biological agents in patients with ankylosing spondylitis: results of a Delphi study by the ASAS Group.

BACKGROUND: There is ample evidence of important symptomatic efficacy of tumour necrosis factor alpha (TNFalpha) inhibition in ankylosing spondylitis (AS). Moreover, studies suggest that anti-TNF could be considered as the first disease controlling antirheumatic treatment (DC-ART) for AS. OBJECTIVE: To determine precisely which patients with AS are most likely to benefit from anti-TNFalpha treatment because of the cost and possible long term side effects of such treatment. METHODS: Assessment in Ankylosing Spondylitis (ASAS) members were asked to use a Delphi technique to name the characteristics of patients with AS for whom they would start DC-ART, in three different clinical presentations (isolated axial involvement, peripheral arthritis, enthesitis). RESULTS: Among the 62 invited ASAS members, more than 50% actively participated in the four phases of definition according to the Delphi technique. For each of the three clinical presentations, a combination of five to six domains was proposed, with an evaluation instrument and a cut off point defining a minimum level of activity for each domain. CONCLUSION: This study provides a profile for a patient with AS for considering initiation of biological agents that reflects the opinion of the ASAS members, using a Delphi exercise. Further studies are required to assess their relevance and their consistency with clinical practice.

Antibodies, Monoclonal↗

Endothelin-1 and nitric oxide in the pathogenesis of urinary tract disorders secondary to bladder outlet obstruction.

Bladder outlet obstruction (BOO) is a common disorder that is associated with urinary tract symptoms. Nitric oxide (NO), synthesized by NO synthase (NOS) is a potent vasodilator that is present throughout the urinary tract and the corpus cavernosum. Endothelin-1 (ET-1) conversely is a potent vasoconstrictor peptide that is similarly distributed throughout the urinary tract. ET-1 and NO as well as possessing opposing actions regulate each other's synthesis. The disruption of the balance between ET-1 and NO is associated with various vascular pathologies. However, their potential roles in the pathogenesis of urinary tract disorders, secondary to BOO, is not well established. New Zealand White rabbits with BOO are considered to be a suitable model of the human condition. Hence, using this model, we systematically investigated the potential roles of ET-1 and NO in the pathogenesis of the various urological disorders associated with BOO. In this review we discuss the results of our studies, which support the concept that an imbalance between ET-1 and NO may be associated with the pathogenesis of urinary tract disorders secondary to BOO. We also discuss the potential clinical implications of this association. This review is based on the Bard Silver Medal Lecture given (by MAK) at the 2002 British Association of Urological Surgeons (BAUS) annual meeting.

Animals↗