Treatment of painful distal sensory polyneuropathy in HIV-infected patients with a topical agent: results of an open-label trial of 5% lidocaine gel.
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Anesthetics, Local↗
Biomedical subjects
A Khan
Publications and source records attributed to A Khan.
Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid. Tuberculosis Trials Consortium.
BACKGROUND: Rifapentine is a cyclopentyl-substituted rifamycin whose serum half-life is five times that of rifampin. The US Public Health Service Study 22 compared a once-weekly regimen of isoniazid and rifapentine with twice weekly isoniazid and rifampin in the continuation phase (the last 4 months) of treatment for pulmonary tuberculosis in HIV-seropositive and HIV-seronegative patients. This report concerns only the HIV-seropositive part of the trial, which has ended. The HIV-seronegative part will stop follow-up in 2001. METHODS: Adults with culture-positive, drug-susceptible pulmonary tuberculosis who completed 2 months of four-drug (isoniazid, rifampin, pyrazinamide, ethambutol) treatment (induction phase) were randomly assigned 900 mg isoniazid and 600 mg rifapentine once weekly, or 900 mg isoniazid and 600 mg rifampin twice weekly. All therapy was directly observed. Statistical analysis used univariate, Kaplan-Meier, and logistic and proportional hazards regression methods. FINDINGS: 71 HIV-seropositive patients were enrolled: 61 completed therapy and were assessed for relapse. Five of 30 patients in the once-weekly isoniazid/rifapentine group relapsed, compared with three of 31 patients in the twice-weekly isoniazid/rifampin group (log rank chi2=0.69, p=0.41). However, four of five relapses in the once-weekly isoniazid/rifapentine group had monoresistance to rifamycin, compared with none of three in the rifampin group (p=0.05). Patients who relapsed with rifamycin monoresistance were younger (median age 29 vs 41 years), had lower baseline CD4 cell counts (median 16 vs 144 microL), and were more likely to have extrapulmonary involvement (75% vs 18%, p=0.03) and concomitant therapy with antifungal agents (75% vs 9%, p=0.006). No rifamycin monoresistant relapse has occurred among 1004 HIV-seronegative patients enrolled to date. INTERPRETATION: Relapse with rifamycin monoresistant tuberculosis occurred among HIV-seropositive tuberculosis patients treated with a once-weekly isoniazid/rifapentine continuation-phase regimen. Until more effective regimens have been identified and assessed in clinical trials, HIV-seropositive people with tuberculosis should not be treated with a once-weekly isoniazid/rifapentine regimen.
AIDS-Related Opportunistic Infections↗
The bisindolylmaleimide protein kinase C inhibitor, Ro 32-2241, reverses multidrug resistance in KB tumour cells.
Ro 32-2241 is a bisindolylmaleimide that selectively inhibits protein kinase C (PKC) as compared with other protein kinases. Experiments were carried out to examine its potential as a multidrug resistance-reversing agent. Ro 32-2241 inhibited efflux, and increased accumulation, of [3H]-daunomycin in multidrug-resistant (MDR) KB-8-5 and KB-8-5-11 cells and had no effect on drug-sensitive KB-3-1 cells. Ro 32-2241 completely reversed the doxorubicin resistance of KB-8-5 and KB-8-5-11 cells, showing no effect on the sensitivity of drug-sensitive KB-3-1 cells. The potency of Ro 32-2241 was comparable with that of cyclosporin A and better than that of verapamil, known modulators of multidrug resistance. Ro 32-2241 also completely reversed the taxol resistance of KB-8-5 cells and partially reversed the resistance of KB-8-5-11 cells. Vinblastine resistance was also partially reversed. Mechanistic experiments were carried out to determine whether Ro 32-2241 interacted with P-glycoprotein (Pgp) directly. Increased efflux of [14C]-Ro 32-2241 was seen with the more resistant KB-8-5-11 cells (although the percentage effluxed was very low as compared with [3H]-daunomycin), suggesting that Ro 32-2241 can act as a substrate for Pgp. Direct interaction of Ro 32-2241 with Pgp was confirmed by demonstration that it inhibited binding of [3H]-azidopine to Pgp in KB-8-5-11 membranes. In conclusion, Ro 32-2241, acting directly on Pgp (rather than, or in addition to, an effect on PKC), is effective in reducing or reversing resistance to doxorubicin, taxol and vinblastine in human tumour cells with a clinically relevant degree of MDR. However, results of in vivo experiments conducted to investigate the effects of Ro 32-2241 on resistance to doxorubicin suggest that it may not be possible to achieve sufficiently high levels of Ro 32-2241 in vivo to modulate MDR.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice.
BACKGROUND: Pathologic interpretation of biopsy specimens of columnar lined esophagus guides subsequent endoscopic surveillance and/or surgical intervention. The aim of this study was to evaluate pathologic interpretation of columnar lined esophagus by general pathologists in community practice. METHODS: Five histologic slides representing different types of columnar lined esophagus were submitted for review by 20 randomly selected general pathologists in community practice. There were three cases with intestinal metaplasia (one with no dysplasia, one with low-grade dysplasia, and one with high-grade dysplasia) and two cases of gastric metaplasia (one fundic-type and one cardia-type). RESULTS: High-grade dysplasia was identified as such by 30% of pathologists and was called invasive adenocarcinoma by 20%, low-grade dysplasia by 30%, and moderate dysplasia by the remaining 20%. Low-grade dysplasia was identified as such by 35% of pathologists and was called high-grade dysplasia by 20%, moderate dysplasia by 20%, and no dysplasia by 25%. Specialized columnar epithelium with no dysplasia was identified as such by 35%, called low-grade dysplasia by 35%, moderate dysplasia by 15%, indeterminate for dysplasia by 10%, and invasive adenocarcinoma by 5%. Gastric metaplasia without specialized columnar epithelium was identified as Barrett's esophagus in 38% of cases. CONCLUSIONS: Pathologic interpretation of columnar lined esophagus by community pathologists may be subject to marked interobserver variation. The term Barrett's esophagus is often used to describe columnar lined esophagus without goblet cells. Because this finding is not clearly associated with an increased risk of cancer, these data support recent suggestions that the term Barrett's esophagus be abandoned. Interpretations of both high-grade and low-grade dysplasia should be considered for review by experts in esophageal pathology.
Barrett Esophagus↗
Unusual and uncommon prostatic lesions.
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Diagnosis, Differential↗
The quest of infertile women in squatter settlements of Karachi, Pakistan: a qualitative study.
OBJECTIVES: There is a dearth of knowledge regarding Pakistani women's perceptions and treatment seeking behavior for infertility. We conducted this study to explore the contextual factors that influence the health-seeking behavior of infertile women in the lower socio-economic group. METHODS: In-depth interviews were conducted with 17 women, identified from clinics and community using pre-tested interview guidelines covering issues as the chronological sequence of the number and types of the health care providers consulted for infertility, household dynamics regarding decision making, perceived causes and social and psychological effects of infertility on the woman and her family. RESULTS: 14 of the 17 women interviewed presented with primary infertility and three with secondary infertility. Reasons reported for seeking treatment for primary infertility were: someone to carry on the family name, feeling alone and akhrat par maan bap bun kar uthna (getting up as a parent on judgment day). Two of the three women suffering from secondary infertility were seeking treatment because they did not have any male offspring. Of the 14 women, 11 initially sought treatment within the first two years of marriage; one woman reported that she was "coerced" by her mother-in-law to seek treatment following the first week of marriage. On average, a woman went to three health care providers (general practitioners, gynecologists and Traditional Birth Attendants) in her quest for assistance. The effects that infertility had on these women ranged from social pressure, coercion by in-laws and/or social isolation. Only one woman reported being put off by sex because it was not giving her what she 'desired'. CONCLUSION: Women in Pakistan seek care for infertility early and go to various types of health care providers. Infertility is usually treated as a clinical disease by the health care providers without considering its social ramifications.
Adaptation, Psychological↗
Limonoids from Swietenia macrophylla and S. aubrevilleana.
An investigation of the seeds of Swietenia macrophylla and S. aubrevilleana (Meliaceae) is reported. Three new compounds, augustineolide (1) and 3beta,6-dihydroxydihydrocarapin (2) from S. macrophylla and 6-acetoxyhumilinolide C (3) from S. aubrevilleana were isolated and characterized along with fifteen known compounds. Four of the compounds were subjected to an antifeedant bioassay on the final instar larvae of Spodoptera frugiperda. The antifeedant activity was comparable to that of bicyclononanolides previously tested.
Animals↗
Import and processing of heart mitochondrial cyclophilin D.
Cyclophilins are a family of cyclosporin-A-binding proteins which catalyse rotation about prolyl peptide bonds. A mitochondrial isoform in mammalian cells, cyclophilin D, is a component of the permeability transition pore that is formed by the adenine nucleotide translocase and the voltage-dependent anion channel at contact sites between the inner and outer membrane. This study investigated the submitochondrial location of cyclophilin D by following the fate of radiolabelled protein following import. Precursor [(35)S]cyclophilin D was expressed in vitro from a PCR-generated cDNA. The precursor was imported by rat heart mitochondria and processed in a single step to a 21-kDa protein that was identical (SDS/PAGE) to an in vitro expressed mature protein and a cyclophilin D purified from rat heart mitochondria. No further modification of the mature protein could be demonstrated. Fractionation of mitochondria following import established that cyclophilin D locates only to the matrix. It is concluded that cyclophilin D binding to the permeability transition pore must occur at the inner face of the mitochondrial inner membrane.
Animals↗
Acute psychotic symptoms induced by topiramate.
The incidence of psychosis during clinical trials of topiramate was 0.8%, not significantly different from the rate for placebo or reported rates of psychosis in patients with refractory epilepsy. We observed psychotic symptoms in five patients soon after initiation of topiramate therapy. We performed a retrospective chart review of the first 80 patients who began on topiramate after approval for clinical use, between January and April 1997. Symptoms suggestive of psychosis, including hallucinations and delusions, were sought for analysis. Cognitive effects such as psychomotor slowing, confusion, and somnolence were not included. Five patients developed definite psychotic symptoms 2 to 46 days after beginning topiramate. Dosages at symptom onset were 50-400 mg/day. Symptoms included paranoid delusions in four patients and auditory hallucinations in three. Symptoms of psychosis and other psychiatric symptoms resolved quickly with discontinuation of topiramate in three patients, dose reduction from 300 to 200 mg/day in one and with inpatient treatment and neuroleptics in another. One patient had a history of auditory hallucinations, one of aggressive and suicidal thoughts, but three had no significant psychiatric history. Physicians should be aware of the possibility of psychotic symptoms, even in patients without a previous psychiatric history, when prescribing topiramate. Symptoms resolve quickly with discontinuation.
Adult↗
Monomorphic teratoma of the ovary: a rare cause of triiodothyronine toxicosis.
A case of low thyroid radioactive iodine uptake (RAIU) thyrotoxicosis due to a large struma ovarii comprising pure thyroid tissue is presented, including a detailed diagnostic evaluation, histopathology, and demonstration of rapid recovery of native thyroid function after surgical excision. In addition, the first comprehensive analysis of thyroglobulin obtained from an ovarian struma is reported.
Aged↗
Sequential chemotherapy and radiotherapy for organ preservation in advanced resectable nonlaryngeal head and neck cancer.
Although there is no definite survival advantage to the use of sequential induction chemotherapy (CT) followed by radiotherapy (RT) in advanced resectable laryngeal cancer, this approach does succeed in preserving the larynx in many of these patients. The authors performed this study to analyze their results using a similar approach for patients with advanced resectable cancer located outside the larynx who would have required a total laryngectomy for oncologic or functional reasons. A retrospective study was performed at a single institution that included all patients with advanced resectable nonlaryngeal head and neck cancer treated with induction CT between January 1990 and August 1995. A total of 19 patients were included, with primary cancers located in the oropharynx in 14 patients, the hypopharynx in four, and the oral cavity and oropharynx in one. Eight patients had clinical stage III disease, and 11 patients had stage IV disease. Our treatment protocol consisted of two cycles of induction CT with cisplatin and 5-fluorouracil, followed by a third cycle of CT and subsequent RT in patients who achieved at least a clinical partial response (PR) after two courses of induction CT. Eighteen of 19 patients were evaluable for response. Overall, 13 patients (72%) had a major response (PR or CR) to induction CT at the primary site, and eight patients (57%) had a major response to chemotherapy in the neck. With a mean follow-up of 53 months (range, 24-71 months), the disease-specific survival was 57% for those patients with cancer of the oropharynx and oral cavity. In the subset of patients with hypopharynx cancer, 3 of 4 patients died of cancer despite achieving major response to induction CT. Organ preservation using sequential CT and RT for advanced resectable nonlaryngeal head and neck cancer is feasible, and the results in our experience with cancer of the oropharynx were similar to those reported for primary laryngeal cancer. Our limited experience using this protocol for cancer of the hypopharynx has been disappointing.
Adult↗
Use of plastic stents for the external drainage of the pancreatic duct at the time of pancreaticoduodenectomy.
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Adult↗
Orthostatic-mediated hypoperfusion in limb-shaking transient ischemic attack.
In patients with severe carotid stenosis or total occlusion, episodic contralateral motor dysfunction is more likely related to cerebral hypoperfusion than epileptogenic activity. A man with orthostatic-mediated right-sided limb shaking was found to have total left internal carotid artery occlusion. There was prominent reduction of cerebrovascular reserve seen on single photon emission computed tomography (SPECT) performed with and without acetazolomide. During assumption of an upright position transcranial Doppler (TCD) revealed a marked attenuation of the left middle cerebral artery flow pattern not associated with changes during electroencephalographic monitoring, even after administration of acetazolomide. In this man, limb shaking episodes were attributed to hypoperfusion of the contralateral cerebral hemisphere, and not to epileptogenic activity.
Carotid Stenosis↗
Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines.
Although accumulating evidence suggests a chemopreventive role for folic acid in colon cancer, the regulation of this process in unknown. We hypothesize that supplemental folic acid exerts its chemopreventive role by inhibiting mucosal hyperproliferation, an event considered to be central to the initiation of carcinogenesis in the gastrointestinal tract. The present investigation examines the effect of supplemental folic acid on proliferation of Caco-2 and HCT-116 colon cancer cell lines. Furthermore, because certain tyrosine kinases, particularly epidermal growth factor receptor (EGFR), play a role in regulating cell proliferation, we also examined the folic acid-induced changes in tyrosine kinase activity and expression of EGFR. In Caco-2 and HCT-116 cells, maintained in RPMI 1640 medium containing 1 microg/ml folic acid, we observed that the supplemental folic acid inhibited proliferation in a dose-dependent manner. Pretreatment of HCT-116 and Caco-2 cell lines with supplemental folic acid (1.25 microg/ml) completely abrogated transforming growth factor-alpha (TGF-alpha)-induced proliferation in both cell lines. Tyrosine kinase activity and the relative concentration of EGFR were markedly diminished in both cell lines following a 24-h exposure to supplemental folic acid. The folic acid-induced inhibition of EGFR tyrosine kinase activity in colon cancer cell lines was also associated with a concomitant reduction in the relative concentration of the 14-kDa membrane-bound precursor form of TGF-alpha. In conclusion, our data suggest that supplemental folic acid is effective in reducing proliferation in two unrelated colon cancer cell lines and that EGFR tyrosine kinase appears to be involved in regulating this process.
Anticarcinogenic Agents↗
Induction of G(1) checkpoint in the gastric mucosa of aged rats.
Although in Fischer 344 rats aging is found to be associated with increased gastric mucosal proliferative activity, little is known about specific changes in the regulatory mechanisms of this process. To determine whether changes in cell cycling events could partly contribute to the age-related rise in gastric mucosal proliferative activity, the present investigation examines changes in cyclin-dependent kinase (Cdk2) activity and the regulation of this process in the gastric mucosa of Fischer 344 rats aged 4 (young), 13 (middle aged), and 24 (old) mo. We observed that aging is associated with a progressive rise in activity and protein levels of Cdk2 in the gastric mucosa. This is also found to be accompanied by a concomitant increase in cyclin E but not cyclin D1 levels. On the other hand, the levels of p21(Waf1/Cip1) (total as well as the fraction associated with Cdk2), a nuclear protein that is known to inhibit different cyclin-Cdk complexes, are found to decline in the gastric mucosa with advancing age. In contrast, with aging, there was a steady rise in p53 levels in the gastric mucosa. We have also observed that the levels of phosphorylated retinoblastoma protein, a form that participates in regulating progression through the S phase, are markedly elevated in the gastric mucosa of aged rats. In conclusion, our data suggest that, in the gastric mucosa, aging enhances transition of G(1) to S phase as well as progression through the S phase of the cell cycle. However, the age-related decline in p21(Waf1/Cip1) in the gastric mucosa appears to be independent of p53 status.
Aging↗
Know your intellectual property rights.
Dismissing intellectual property rights as someone else's responsibility may not be prudent. It can jeopardize a company's future business because any new product could be unprotected, or even worse, belong to someone else. This article explains how a little strategic planning and due diligence can help prevent unnecessary legal costs. Much of a company's value can be tied up in intangible assets such as patents, trademarks and copyright, and an intellectual property audit helps assess its true worth.
Equipment and Supplies↗
Scorpion--stings the limb and stuns the heart?
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Animals↗
Development of a sensitive and quantitative analytical method for 1H-4-substituted imidazole histamine H3-receptor antagonists utilizing high-performance liquid chromatography and dabsyl derivatization.
A sensitive and versatile analytical method utilizing high-performance liquid chromatography (HPLC) and precolumn derivatization of 1H-4-substituted imidazole compounds is described. A HPLC method using 4-dimethylaminoazobenzene-4'-sulfonyl chloride (dabsyl chloride) and ultraviolet (UV) detection was developed for the analysis of histamine (HA) H3-selective compounds in human plasma, rat plasma, or homogenized rat cortical tissue. The average intra- and inter-assay variability, over a range of 10 to 0.01 microg/ml, was determined to be acceptable. The lower limit of detection for the dabsylated ligands was estimated to be <1.0 ng/ml while the lower limit of quantitation (LLOQ) was determined to be 10 ng/ml of conjugate. This assay has demonstrated it's suitability for the sensitive quantitation of several structurally diverse 1H-4-substituted imidazole HA H3-receptor antagonists in biological matrices for pharmacokinetic and biodistribution studies.
Animals↗