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Biomedical subjects

W A Khan

Publications and source records attributed to W A Khan.

At least 37 records · Page 2Linked to original sources
PubMed1997

A prospective phase II trial to evaluate the efficacy and toxicity of hepatic arterial infusion of ifosfamide in patients with inoperable localized hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common tumor in the developing countries. Most patients present with relatively advanced disease and have a poor survival. Due to lack of any effective therapy, there is an urgent need to investigate new drugs. We conducted a prospective trial to evaluate the efficacy and tolerability of ifosfamide (IFEX) in patients with histologically proved, inoperable, localized HCC. Eligibility criteria included World Health Organization (WHO) performance status (PS) of 0-2, bilirubin < or = 3.0 mg/dl, albumin > or = 2.5 g/dl, creatinine < or = 2.0 mg/dl, correctable coagulation profile, adequate bone marrow function, and no prior therapy. Hepatic arterial infusion of IFEX (6 g/m2) was given continuously over 96 hours. Mesna was given intravenously, in same doses, throughout IFEX infusion and for 12 hours afterwards. Nineteen patients were enrolled in the trial. Mean age was 51.1 years and all were men. Most of the patients had PS 1. The majority had viral hepatitis and cirrhosis. Eleven had raised serum alpha fetoprotein (AFP) levels. Thirteen patients had multiple lesions involving both lobes of the liver. Mean size of ultrasonographically evident largest lesion was 11.0 cm. Three patients are inevaluable; one died early, one refused further therapy, and another was lost to follow-up. Among the 16 evaluable patients, 6 (37.5%) had partial remission and 4 (25%) had a minor response. An additional four (25%) patients had stable disease. Only two (12.5%) patients had progression of disease while on therapy. Overall response rate (partial plus minor) was 62.5%. Mean duration of partial response was 5.0 months and mean survival was 7.1 months. Subjective improvement in pain was observed in all but two patients and correlated well with the objective response. Chemotherapy-related side effects were predominantly grade III-IV anemia and alopecia. Three patients had catheter-related complications (one local infection, one bleeding, and one thrombosis). Two patients developed mild encephalopathy and two had hepatic decompensation as evidenced by worsening liver function tests. The results of this pilot study suggest that IFEX, given as a continuous hepatic arterial infusion, is an active drug in inoperable localized HCC. Toxicity is manageable. This drug deserves further trials to properly evaluate its therapeutic potential.

Adult↗
PubMed1997

Histopathological variations among cases of Wilms' tumor in Bangladesh and its relationship with prognosis.

Recent advancement in the cytopathologic features produced a number of variants of Wilms' tumor which are the primary determinant of survival of Wilms' tumor patients. This study was carried out with 47 patients of Wilms' tumor in different stages in three selected hospitals from 1991 to 1993. Among them 61.7% (29) were in Favorable histopathology and 38.3% (18) were in Unfavorable histopathology group. After managing the patients with multimodal therapy according to the protocol of National Wilms' tumor Study-III the favorable group had shown better prognosis. The difference between two groups was statistically significant (chi-square = 3.2, P < 0.05). Histopathological variations could be easily determined which might improve the overall prognosis of Wilms' tumor.

Anaplasia↗
PubMed1996

Randomised controlled comparison of single-dose ciprofloxacin and doxycycline for cholera caused by Vibrio cholerae 01 or 0139.

BACKGROUND: Effective antimicrobial therapy can reduce the duration and volume of cholera diarrhoea by half. However, such treatment is currently limited by Vibrio cholerae resistance to the drugs commonly prescribed for cholera, and by the difficulties involved in the administration of multi-drug doses under field conditions. Because of its favourable pharmacokinetics we thought it likely that single-dose ciprofloxacin would be effective in the treatment of cholera. METHODS: In this double-blind study treatment was either a single 1 g oral dose of ciprofloxacin plus doxycycline placebo, or a single 300 mg oral dose of doxycycline plus ciprofloxacine placebo. 130 moderately or severely dehydrated men infected with V cholerae 01 and 130 infected with V cholerae 0139 were randomly assigned treatment. Patients stayed in hospital for 5 days. We measured fluid intake and stool volume every 6 h, and a sample of stool for culture was obtained daily. The primary outcome measures were clinical success--the cessation of watery stool within 48 h; and bacteriological success--absence of V cholerae from cultures of stool after study day 2. FINDINGS: Among patients infected with V cholerae 01, treatment was clinically successful in 62 (94%) of 66 patients who received ciprofloxacin and in 47 (73%) of 64 who receive doxycycline (difference 21% [95% Cl 8-33]); the corresponding proportions with bacteriological success were 63 (95%) and 44 (69%) (27% [14-39]). Among patients infected with V cholerae 0139, treatment was clinically successful in 54 (92%) of 59 patients who received ciprofloxacin and in 65 (92%) of 71 who received doxycycline (< 1% [-9 to 9]), and bacteriologically successful in 58 (98%) and 56 (79%), respectively (19% [9-30]). Total volume of watery stool did not differ significantly between ciprofloxacin-group and doxycycline-group patients infected with either V cholerae 01 or 0139. All but one of the V cholerae 01 and all of the 0139 isolates were susceptible in vitro to doxycycline, whereas 48 (37%) of the V cholerae 01 isolates and none of the 0139 isolates were resistant to tetracycline. Treatment clinically failed in 14 (52%) of 27 doxycycline-treated patients infected with a tetracycline-resistant V cholerae 01 strain, compared with three (8%) of 37 patients infected with a tetracycline-susceptible strain (44% [23-65]). INTERPRETATION: Single-dose ciprofloxacin is effective in the treatment of cholera caused by V cholerae 01 or 0139 and is better than single-dose doxycycline in the eradication of V cholerae from stool. Single-dose ciprofloxacin may also be the preferred treatment in areas where tetracycline-resistant V cholerae are common. In V cholerae, in-vitro doxycycline susceptibilities are not a useful indicator of the in-vivo efficacy of the drug.

Administration, Oral↗
PubMed1996

Interpretation of the Widal test in the diagnosis of typhoid fever in Bangladeshi children.

The value of a Widal test in diagnosing typhoid fever was assessed in children aged between 1 and 10 years in Bangladesh. The test was done on sera specimens from 300 healthy school children, 100 patients with non-typhoidal febrile illness and 150 bacteriologically proven cases of typhoid fever. Salmonella typhi O and H agglutinin titres > 1:80 and > 1:160 were considered to be significant with 88% sensitivity and 98% specificity, respectively. Among the bacteriologically proven cases, 11.3% showed no response to either agglutinin, and in another 17.3% of cases there was no response for TO agglutinin. This study suggests that in children in an endemic area a positive Widal test is of considerable importance in diagnosing typhoid fever. Furthermore, negative results should be interpreted with caution and both the agglutinins must be considered equally important. Reliance on somatic (TO) antigen only will result in missed diagnosis.

Agglutination Tests↗
PubMed1996

Erythromycin and trimethoprim-sulphamethoxazole in the treatment of cholera in children.

To evaluate the efficacy of erythromycin and trimethoprim-sulphamethoxazole (TMP-SMX) in the treatment of cholera in children aged 1-8 years, a randomised clinical trial was conducted at a diarrhoea treatment centre in Bangladesh from December 1991 to June 1992. Fifteen children received erythromycin, 50 mg/kg per day, in four equally divided doses, 18 children received 10 mg/kg per day of trimethoprim and 50 mg/kg per day of sulphamethoxazole in two equally divided doses (12 hourly) for five days, and 15 children received no antibiotic; children in all three groups received intravenous cholera saline for severe dehydration and for mild to moderate dehydration, a rice-based oral rehydration solution. The mean stool volumes in mL/kg body weight in the two treatment groups were less than that of the control group, and there were no significant differences in stool volume among the two treatment groups. However, 67% of the children in the erythromycin group and 82% in the TMP-SMX group recovered within 72 hours compared to 33% in the control group (p < 0.01). Similarly, the bacteriological cures were 80% in the erythromycin group and 83% in the TMP-SMX group compared to only 27% in the control group (p < 0.001). These results confirm that both erythromycin and trimethoprim-sulphamethoxazole are effective antimicrobials in the treatment of cholera. These drugs are of value specially in younger children in whom tetracycline is contraindicated or when the infecting Vibrio cholerae are resistant to tetracycline.

Anti-Bacterial Agents↗
PubMed1995

Treatment of shigellosis: IV. Cefixime is ineffective in shigellosis in adults.

OBJECTIVE: To compare the efficacy of cefixime with that of pivamdinocillin in the treatment of adults with acute dysentery caused by Shigella infection. DESIGN: Randomized, double-blind clinical trial. SETTING: A diarrhea treatment center in Dhaka, Bangladesh. PATIENTS: 30 men with dysentery lasting 72 hours or less. INTERVENTIONS: Patients were randomly assigned to receive either 400 mg of cefixime every 24 hours (n = 15) or 400 mg of pivamdinocillin every 6 hours (n = 15) for 5 days. All patients were hospitalized for 6 days. Patients in whom initial drug therapy failed received alternative antimicrobial therapy. MEASUREMENTS: Physical examinations were done and symptoms were recorded daily, and body temperatures were measured every 6 hours. Stools were counted and examined for consistency and for the presence of blood and mucus. Therapy failed if symptoms of dysentery persisted for more than 72 hours or if, on study day 5, a patient had six stools, one watery or bloody-mucoid stool, or an oral temperature higher than 37.8 degrees C. Bacteriologic failure of therapy occurred if Shigella could be isolated from a stool sample on or after study day 3. RESULTS: Therapy failed in seven (47%) patients given cefixime but in none of the patients given pivamdinocillin (P = 0.006). Patients given cefixime had longer duration of fever (median, 6 hours compared with 0 hours, P = 0.019), longer duration of the period with dysenteric stools (median, 4 days compared with 1 day, P = 0.001), and more stools during the 6 study days (median, 65 compared with 28, P = 0.002) than patients treated with pivamdinocillin. Bacteriologic failure of therapy occurred in 60% of patients (9 of 15) given cefixime and 13% of those (2 of 15) given pivamdinocillin (P = 0.009). CONCLUSION: Cefixime is ineffective in treating shigellosis in adults when used in the standard recommended dosage.

Adolescent↗
PubMed1995

12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated hydrolysis of inositol phospholipids.

Protein kinase C (PKC) isoenzymes are essential components of cell signaling. In this study, we investigated the regulation of PKC-alpha in murine B16 amelanotic melanoma (B16a) cells by the monohydroxy fatty acids 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and 13(S)-hydroxyoctadecadienoic acid [13(S)-HODE]. 12(S)-HETE induced a translocation of PKC-alpha to the plasma membrane and focal adhesion plaques, leading to enhanced adhesion of B16a cells to the matrix protein fibronectin. However, 13(S)-HODE inhibited these 12(S)-HETE effects on PKC-alpha. A receptor-mediated mechanism of action for 12(S)-HETE and 13(S)-HODE is supported by the following findings. First, 12(S)-HETE triggered a rapid increase in cellular levels of diacylglycerol and inositol trisphosphate in B16a cells. 13(S)-HODE blocked the 12(S)-HETE-induced bursts of both second messengers. Second, the 12(S)-HETE-increased adhesion of B16a cells to fibronectin was sensitive to inhibition by a phospholipase C inhibitor and pertussis toxin. Finally, a high-affinity binding site (Kd = 1 nM) for 12(S)-HETE was detected in B16a cells, and binding of 12(S)-HETE to B16a cells was effectively inhibited by 13(S)-HODE (IC50 = 4 nM). In summary, our data provide evidence that regulation of PKC-alpha by 12(S)-HETE and 13(S)-HODE may be through a guanine nucleotide-binding protein-linked receptor-mediated hydrolysis of inositol phospholipids.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1995

Arachidonic acid and free fatty acids as second messengers and the role of protein kinase C.

In addition to serving as the precursor to a plethora of eicosanoids and other bioactive molecules, arachidonate may function as a bona fide second messenger. A number of studies have documented the ability of arachidonate to regulate the function of multiple targets in vitro systems. This has been particularly well established and studied with the activation of protein kinase C by arachidonate in a mechanism distinct from activation by diacylglycerol. In cells, arachidonate induces a number of activities, many of which may be independent of further metabolism to eicosanoids; suggesting possible direct action of arachidonate. This review summarizes the current state of knowledge on the possible second messenger function of arachidonate with specific emphasis on the regulation of protein kinase C.

Animals↗
PubMed1995

Feasibility of outpatient management of fever in cancer patients with low-risk neutropenia: results of a prospective randomized trial.

PURPOSE: We recently demonstrated the efficacy of single-agent oral ofloxacin in the management of hospitalized neutropenic febrile patients. Ofloxacin was particularly effective in patients with short duration of neutropenia and fever of undetermined origin. These results prompted us to study the feasibility of outpatient management of neutropenic febrile patients who are otherwise at low risk of morbidity and mortality. PATIENTS AND METHODS: This multi-institutional, prospective, randomized trial included 182 low-risk neutropenic febrile episodes. After an initial work-up for fever, patients were randomized to receive oral ofloxacin 400 mg immediately and twice daily thereafter in the hospital or as outpatients. Close monitoring and follow-up were carried out in all patients. Those who failed to respond and remained febrile were given parenteral antibiotics. Nonresponding outpatients were admitted to the hospital for parenteral therapy. RESULTS: One hundred sixty-nine episodes were evaluable. The hospital and outpatient treatment groups had comparable clinical characteristics. Pyrexias of undetermined origin (PUO) comprised 69% of episodes managed in hospital and 73% of episodes treated outside. The success rate with PUO was similar with inpatient and outpatient management. Patients with clinical and microbiologic infections fared less well than those with PUO. Overall, 78% of inpatient and 77% of outpatient fevers resolved with no modification of the initial treatment. Twenty-one percent of patients originally assigned to outside management required hospitalization. Mortality was 2% among inpatients and 4% among outpatients. One early death in a nonhospitalized patient underscores the need for close monitoring and surveillance in these cases. CONCLUSIONS: Outpatient management of low-risk neutropenic febrile patients with ofloxacin is as effective as inpatient management with the same agent. This approach should be limited to the subset of patients with low-risk factors who are not otherwise on quinolone prophylaxis.

Adult↗
PubMed1995

Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial.

Nausea and vomiting are extremely common and most distressing side effects of high-dose cisplatin therapy. Cisplatin induces anticipatory and acute, as well as, delayed emesis. High doses of metoclopramide can effectively decrease the intensity of these symptoms in up to 70% of cases. Several agents, including dexamethasone and antihistamines have been demonstrated to either increase the efficacy of metoclopramide or decrease the side effects. Lorazepam, a benzodiazepine, has both antiemetic and anxiolytic properties. It can be useful as an adjunct to metoclopramide-based therapy. We conducted a randomized trial to evaluate the efficacy of lorazepam in managing anticipatory, acute, and delayed emesis induced by high doses of cisplatin. A total of 180 events involving cisplatin administration (100 mg/m2 as a 24-hour continuous infusion) were randomized to receive metoclopramide along with dexamethasone and clemastine with and without lorazepam. Categorical scales were utilized to document the incidence of nausea and vomiting and side effects related to antiemetic therapy. All episodes are evaluable. Lorazepam significantly reduced the incidence of anticipatory nausea and vomiting (P < .05) as well as acute emesis (P = .05) induced by cisplatin. Delayed emesis was also decreased; however, it was statistically significant on day 3 only (P < .05). Side effects were few except for mild sedation and amnesia, which were significantly more common in those receiving lorazepam (P < .001). We conclude that lorazepam increases the efficacy of metoclopramide against cisplatin-induced anticipatory, acute, and delayed nausea and vomiting. This four-drug regimen may offer one of the best combinations to be utilized in comparative trials against the newly introduced serotonin antagonists.

Adult↗
PubMed1995

C reactive protein and prealbumin as markers of disease activity in shigellosis.

To evaluate serum C reactive protein (CRP) and prealbumin concentrations as markers of disease activity in shigellosis this study serially measured serum concentrations of CRP and prealbumin in 39 patients infected with Shigella spp, and a comparison group of 10 patients infected with Vibrio cholerae serotype 01. On admission, patients with shigellosis had significantly higher median concentrations of CRP (109 v 5 mg/l; p < 0.01) and significantly lower median concentrations of prealbumin (16 v 23 mg/l; p < 0.01) than did patient with cholera. Among Shigella spp infected patients, CRP concentrations were significantly lower, and prealbumin concentrations significantly higher, on study days 3 and 5 when compared with admission values. Among Shigella spp infected patients, those in whom treatment failed had higher admission CRP concentrations than those in whom treatment was successful (p = 0.142). An admission CRP concentration > or = 110 mg/l had a 70% sensitivity and a 61% specificity in predicting failure of treatment among patients infected with Shigella spp; the predictive value of a positive and negative test was 14% and 96% respectively. In summary, acute shigellosis elicits an acute phase response, the magnitude of which predicts clinical outcome.

Acute Disease↗
PubMed1994

Identification, partial purification, and characterization of a novel phospholipid-dependent and fatty acid-activated protein kinase from human platelets.

A novel lipid-dependent protein kinase in human platelets was partially purified and characterized. This enzyme was calcium-independent and was selective for phosphatidic acid as a cofactor/activator with initial activation observed at approximately 2 mol % and peak activity achieved at 4 mol % phosphatidic acid. In the presence of phosphatidylserine, enzyme activation was observed with concentrations of phosphatidic acid as low as 0.5 mol % with peak activity at 2 mol %. Other anionic phospholipids also activated the enzyme but to a lesser extent and with less potency. Enzyme activity was independent of diacylglycerol or phorbol esters and the enzyme did not bind [3H]phorbol dibutyrate. In a soluble protein kinase assay, the enzyme was activated by cis-unsaturated fatty acids with maximum activation occurring at 5-10 microM sodium oleate. Western blot analysis showed that this enzyme did not cross-react immunologically with antibodies raised against the currently identified isoenzymes of protein kinase C. A number of additional biochemical criteria distinguished this enzyme from known isoenzymes of protein kinase C. These biochemical and immunologic data define a novel lipid-dependent protein kinase in human platelets. The role of this enzyme in signal transduction as a phosphatidic acid-activated enzyme and as a possible target for cis-unsaturated fatty acids is discussed.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Self-administered antibiotic therapy for chemotherapy-induced, low-risk febrile neutropenia in patients with nonhematologic neoplasms.

A multicenter prospective nonrandomized trial was conducted to evaluate the efficacy of self-administered oral ofloxacin in the treatment of cancer patients with fever and neutropenia. Patients receiving chemotherapy who either resided far away and were unable to reach the oncology ward within 12 hours of the onset of fever or were unable to afford the expensive inpatient care were eligible for inclusion in the study. Requirements for enrollment included an absolute neutrophil count of < or = 0.5 x 10(9)/L, temperature of > 38 degrees C, and the ability to take oral medications. The patients were instructed to immediately self-administer oral ofloxacin on recognition of fever and to maintain daily telephonic contact with the oncology staff. One-hundred eleven such episodes were evaluable. Neutropenia was mostly of short duration (87% of episodes, < or = 1 week); 92 (83%) of the febrile episodes responded to ofloxacin with resolution of fever and neutropenia (hospitalization was not required). Two episodes resulted in death before the patients could be brought to the hospital; 17 (15%) did not respond to ofloxacin, and the patients required hospitalization. The conditions of all except one improved with parenteral combination antibiotic therapy. No toxicity was observed, and the cost of therapy was negligible. Treatment with oral ofloxacin may possibly serve as an alternative to hospitalization for those who are otherwise at low risk of morbidity and death.

Administration, Oral↗
PubMed1994

Fatal sepsis due to Pseudomonas cepacia.

Pseudomonas cepacia is known as an opportunistic pathogen in the patients with altered host defence. We report a case of hospital-acquired fatal sepsis due to P. cepacia in a child with no known defect in immune system. Virulence of the organism was indicated by the high magnitude of septicaemia. The organism was successfully eliminated by ceftriaxone but the patient died of renal failure.

Bacteremia↗
PubMed1993

Heterogeneity of protein kinase C-mediated rapid regulation of Na/K-ATPase in kidney epithelial cells.

Na/K-ATPase in renal epithelium is expressed at the basolateral surface and thus is critical for vectorial solute transport. One potential mode of regulation of Na/K-ATPase involves the intracellular effector protein kinase C (PKC). In kidney cell lines, activation of PKC by the phorbol ester phorbol 12,13-dibutyrate (PDBu) (1 microM) inhibited Na/K-ATPase transport activity in OK cells (Vmax decreased 42%; p < 0.02), but not in LLC-PK1 cells. By immunoblot, both cell types expressed detectable levels of PKC alpha and PKC sigma. In response to PDBu, PKC alpha translocated from the cytosol to the membrane fractions of both cell lines. Phorbol ester treatment increased incorporation of 32PO4 in multiple substrates in both cell types, but a approximately 109-kDa substrate with neutral pI was detected only in the OK cell. Anti-LEAVE, directed against a highly conserved sequence in the H4-H5 loop of all known alpha isoforms of Na/K-ATPase, recognized a approximately 109-kDa membrane protein from both cell lines. Anti-LEAVE also identified a protein that comigrated with the large phosphoprotein which was only present in OK cells. Following 32PO4 loading and PDBu treatment, anti-LEAVE immunoprecipitated a approximately 109-kDa phosphoprotein in OK but not LLC-PK1 cells. These data support the notion that PKC is capable of phosphorylating the alpha subunit and inhibiting Na/K-ATPase transport activity in intact renal cells. Furthermore, they suggest that some forms of Na/K-ATPase in the kidney are not susceptible to PKC phosphorylation and that this heterogeneity may contribute to response diversity.

Amino Acid Sequence↗