Clearance of psoriasis following agranulocytosis.
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Agranulocytosis↗
Biomedical subjects
S Pai
Publications and source records attributed to S Pai.
Hairy cell leukemia--results with alpha interferon therapy.
Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder. Although now multiple treatment options are being available, the optimal treatment of this disease still remains debatable. Inspite of the advent of newer purine analogues, in India recombinant interferon is the only freely available first line treatment. We report our experience of long term remissions in HCL with interferon alpha 2a. Of a total of 35 cases of HCL we were able to treat 19 cases with interferon. Of 18 evaluable cases an overall response of 88.9% was achieved. With a median follow up of 31 months a disease free survival was 83%. Thus with a dose of 3 million units s.c. daily for 6 months at least, we feel that a reasonably good long term remission can be obtained. The cost of the treatment however, is still a deterrent.
Adult↗
Lovastatin for X-linked adrenoleukodystrophy.
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Adrenoleukodystrophy↗
Trisomy 12 in chronic lymphocytic leukemia--geographical variation.
Incidence of trisomy 12 was studied in 60 cases of chronic lymphocytic leukemia (CLL) with chromosome 12 specific alpha-satellite DNA probe by fluorescence in situ hybridization (FISH). Trisomy 12 was observed in 37 (61.8%) patients. Cells with trisomy 12 were detected in a varying proportion, ranging from > 2% to 86%. Patients with trisomy 12 were predominantly observed with total white blood cell (WBC) count > 80 x 10(9) l(-1) (P < 0.001). In addition, the percentage of trisomy 12 positive lymphocytes correlated with the high WBC counts. Trisomy 12 was observed equally in typical and atypical CLL. 90% of our patients were in the intermediate and high risk groups. It was seen that there was significantly higher percentage of trisomy 12 positive lymphocytes ( > 10%) in the high risk groups (P < 0.05). A higher incidence of FMC7 positivity in atypical CLL was seen in our study. However, there was no significant relationship found between trisomy 12 positivity and expression of either FMC7 or CD23 in our cases. It appears that the CLL that we see at our centre is at a different phase of evolution and perhaps biologically different compared to the CLL seen in the West.
Adult↗
Avascular necrosis of bone--a complication of aggressive therapy for acute lymphoblastic leukemia.
The purpose of the present paper was to report cases of avascular necrosis of bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic leukemia (ALL). X-rays and 99mtechnicium-MDP bone scans were performed on patients with symptoms of bone pain, whereby five patients out of 850 patients were detected to have avascular necrosis of the femoral head. All had received aggressive chemotherapy with steroids. Two patients were still on therapy for the primary disease. In these patients further chemotherapy was continued without steroids. The median period from diagnosis of ALL to development of AVNB was 29 months. Three patients underwent corrective surgical procedures. To conclude, the data suggest that patients receiving combination chemotherapy, especially those with high cumulative doses, run a risk of developing AVNB. Awareness of this complication is important in order to have an early diagnosis so as to limit disability.
Adolescent↗
Evaluation of a new sealed reentrant well chamber for HDR and LDR brachytherapy calibrations.
A new reentrant ionization chamber SNC 1008 has been introduced for low dose rate (LDR) and high dose rate (HDR) brachytherapy source calibrations. There is no air density correction requirement for the chamber since it is hermetically sealed. In this study we evaluate its use for HDR as well as LDR source calibrations. The magnitude of the ionization current collected was found to be independent of the sign of the polarizing voltage within +/- 0.5%. The axial response curve of the well chamber reveals a "plateau region" (+/- 0.5% dose variation) of 4.2 cm, which is larger than the published values for other commercially available chambers. Long-term stability of the chamber was evaluated. Short-term response and source positioning reproducibility were tested using both LDR and HDR sources. Ion collection efficiency was found to be high, making the chamber suitable for HDR 192Ir sources.
Brachytherapy↗
The use of improved radiochromic film for in vivo quality assurance of high dose rate brachytherapy.
GAFChromic film has become increasingly popular for radiation dosimetry. In this study we explore the use of GAFChromic film as an in vivo dosimeter for quality assurance (QA) of fractionated high dose rate 192Ir treatments. Accuracy of dose distribution is explored for the simple vaginal cylinder geometry for which the dose can be easily calculated for comparison. Source dwell times for several patients were optimized to deliver 500 cGy at 0.5 cm from the surface of the vaginal cylinder applicator using a commercial treatment planning system. GAFChromic film was taped to the vaginal cylinder applicator and was enclosed in a leak proof rubber sleeve prior to its insertion. Optical densities were measured along the film at 2 mm spacing, using a densitometer with filtered red light. Density corrections for transient film darkening effects were made and optical densities were converted to absorbed dose in cGy. In vivo patient dose distribution measured for different patients and different fractions were compared with the calculated values along the applicator surface. The variation between the calculated and measured dose was +/- 10%. the reproducibility of dose measurement for different fraction was within +/- 5%. This study demonstrates the potential usefulness of the film as an in vivo for brachytherapy QA.
Administration, Intravaginal↗
A new genetic algorithm technique in optimization of permanent 125I prostate implants.
Real time optimized treatment planning at the time of the implant is desirable for ultrasound-guided transperineal 125I permanent prostate implants. Currently available optimization algorithms are too slow to be used in the operating room. The goal of this work is to develop a robust optimization algorithm, which is suitable for such application. Three different genetic algorithms (sGA, sureGA and securGA) were developed and compared in terms of the number of function evaluations and the corresponding fitness. The optimized dose distribution was achieved by searching the best seed distribution through the minimization of a cost function. The cost function included constraints on the periphery dose of the planned target volume, the dose uniformity within the target volume, and the dose to the critical structure. Adjustment between the peripheral dose, the dose uniformity and critical structure dose can be achieved by varying the weighting factors in the cost function. All plans were evaluated in terms of the dose nonuniformity ratio, the conformation number and the dose volume histograms. Among these three GA algorithms, the securGA provided the best performance. Within 2500 function evaluations, the near optimum results were obtained. For a large target volume (5 cm x 4 cm x 4.5 cm) including urethra with 20 needles, the computer time needed for the optimization was less than 5 min on a HP735 workstation. The results showed that once the best set of parameters was found, they were applicable for all sizes of prostate volume. For a fixed needle geometry, the optimized plan showed much better dose distribution than that of nonoptimized plan. If the critical structure was considered in the optimization, the dose to the critical structure could be minimized. In the cases of irregular and skewed needle geometry, the optimized treatment plans were almost as good as ideal needle geometry. It is concluded that this new genetic algorithm (securGA) allows for an efficient and rapid optimization of dose distribution, which is suitable for real time treatment planning optimization for ultrasound-guided prostate implant.
Algorithms↗
Cardiovascular effects after inhalation of large doses of albuterol dry powder in rats, monkeys, and dogs: a species comparison.
Albuterol is a quickly acting beta-2 adrenergic agonist bronchodilator widely used by asthmatics. Because recent case-control studies have suggested a relationship between the increase in mortality of asthmatics over the past decade and the use of beta 2-adrenergic agonists in the control of asthma, concern has developed regarding the potential cardiotoxicity of beta 2-specific adrenergic agonists, including albuterol. The aim of this investigation was to assess the potential for cardiotoxicity of inhaled albuterol dry powder in rats, monkeys, and dogs. All species were exposed to an aerosol of albuterol 1 h per day, 7 days per week, for at least 2 weeks. Control groups were exposed to filtered conditioned air and handled in the same manner as the albuterol-exposed animals. Plasma concentrations of albuterol confirmed systemic exposure. The daily inhaled dose received by the animals was calculated based on measured respiratory minute volumes, published respiratory tract deposition data, as well as HPLC-determined particle size distribution data and aerosolized albuterol concentrations. Multiples of the maximum daily clinical dose (presentation of 15 micrograms/kg in a 70-kg human) were approximately 0.25- to 2500-fold in the rat, 9- to 100-fold in the monkey, and 0.5- to 90-fold in the dog. No findings attributed to albuterol were observed in the monkey. Tachycardia and transient hypokalemia occurred in rats at multiples of 1.5 times or greater of the maximum clinical dose. Absolute and relative heart weights increased in rats receiving multiples of 47 times or greater of the maximum human dose. In the absence of histopathologic findings, the increases in rat heart weights were considered a physiologic hypertrophic response to tachycardia. In dogs tachycardia and transient hypokalemia occurred at all doses tested. Slight to mild fibrosis in the papillary muscles of the left ventricle of the heart occurred in dogs at multiples > or = 19 times the clinical dose. The cardiovascular effects observed were consistent with the known pharmacologic action of beta 2-adrenergic agonists. Due to the lack of toxicologically relevant findings in rats and monkeys and the wide safety margin in dogs, the findings in this study do not suggest a cardiotoxicity risk in the human population after repeated exposures to clinical doses of albuterol currently used in the treatment of asthma.
Administration, Inhalation↗
Treatment of stable vitiligo with autologous epidermal grafting and PUVA.
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Combined Modality Therapy↗
Preliminary report of an intensified, short duration chemotherapy protocol for the treatment of pediatric non-Hodgkin's lymphoma in India.
BACKGROUND: In the past, the results of the treatment of non-Hodgkin's lymphomas (NHL) in Indian children have been poor, due to inadequate chemotherapy and poor supportive care. In an attempt to overcome these problems, we conducted a clinical trial in Bombay with a new protocol, MCP842. PATIENTS AND METHODS: Seventy-four previously untreated patients < 25 years were entered on study at the Tata Memorial Hospital, Bombay. Patients with lymphoblastic lymphoma (LL) (38) without bone marrow involvement and all patients with small noncleaved cell lymphoma (SNCL) (18) and large cell lymphoma (LCL) (18) were eligible. Treatment consisted of alternating cycles of two regimens, A and B. Patients with St. Jude stages I and II received six cycles, and those with stages III or IV received eight cycles. A cycles included cyclophosphamide, adriamycin, vincristine and ara-C, and B cycles, etoposide, vincristine, methotrexate, ifosfamide and mesna. RESULTS: Complete response was achieved in 67 (91%) of patients. Event free survival (EFS) for all patients was 58%; 68% for patients with SNCL and LCL combined, and 48% for patients with LL. There was no significant difference in EFS by histology (LL versus non-LL), or stage. There were nine (12%) toxic deaths, two during induction and seven in patients in remission; six occurred in patients with LL. CONCLUSIONS: These results are better than past results in Bombay. Unlike earlier CCG protocols, in which the outcome between patients with LL and non-LL differed, this was not so in MCP842. Even patients with extensive LL without bone marrow disease received only eight cycles of therapy, suggesting that short duration therapy is curative in as many as half of such patients--an important observation in a country with limited resources.
Adolescent↗
Single-dose pharmacokinetics of felbamate in patients with renal dysfunction.
AIMS: The purpose of this study was to evaluate the effects of renal impairment on the single-dose pharmacokinetics of the antiepileptic felbamate. METHODS: Twelve subjects with three levels of renal dysfunction (creatinine clearance > 30-80, > 10-30 or 5-10 m min(-1)) and four controls with normal renal function (creatinine clearance > 80 ml min(-1) were studied). Plasma and urine samples were obtained for 144 h following administration of a single 1200 mg dose. RESULTS: Compared with controls, apparent total body clearance, renal clearance and urinary excretion of felbamate were decreased, and half-life, Cmax and AUC values were increased in subjects with renal dysfunction. The magnitude of these changes was associated with the degree of renal dysfunction. Nonrenal clearance and apparent volume of distribution values were also lower in renal dysfunction subjects, but there was no association between the extent of these changes and degree of renal dysfunction. Renal clearance of felbamate accounted for approximately 30% of apparent total body clearance in the control group and from 9-22% in the renal failure patients. Renal clearance of felbamate was significantly correlated with creatinine clearance (r = 0.75; P< 0.001). CONCLUSIONS: These data suggest that initial dosage and titration of felbamate may require adjustment in patients with renal dysfunction.
Adult↗
The investigation of 32P wire for catheter-based endovascular irradiation.
The dose distribution from a 32P source has been measured and calculated in order to evaluate its application in endovascular irradiation. The source dimension was 27 mm in length and 0.3 mm in diameter and was embedded in the end of a Ni-Ti wire. Dose measurements were performed using radiochromic film in several specially designed tissue equivalent phantoms. Loevinger's point dose kernel was used for the calculation. The approximate dose rate at a radial distance of 1.5 mm from the center of the source was found to be 6.75 cGy/s per GBq (0.25 cGy/s per mCi), which allows the delivery of a therapeutic dose in a short time interval with a satisfactory homogeneity without stepping the source. However, the dose rate falls off almost exponentially along the radial distance. Therefore it may not be suitable for treating large diameter vessel from a centrally located source. The effect of a curved 32P wire source on the radial dose distribution was also investigated. The results showed that for a maximum bend of 180 degrees the dose rate was increased by as much as 20% along the inner radial distance but decreased by as much as 20% along the outer radial distance compared to the dose along a straight wire. However, for curvatures normally encountered in a clinical situation, the dose rate was changed less than 5%.
Angioplasty, Balloon, Coronary↗
Novel and frequent mutations of hepatitis B virus coincide with a major histocompatibility complex class I-restricted T-cell epitope of the surface antigen.
We examined the full-length hepatitis B virus (HBV) envelope (surface antigen or HBV small surface antigen [HBsAg]) sequences of 12 different liver samples from 10 different hepatoma-containing chronic carriers. Surprisingly, novel and frequent mutations occurred predominantly at amino acids 40 and 47 of HBsAg, in addition to within a known protective B-cell epitope (so-called group a determinant of HBsAg 124-148). Approximately 58% of chronic carriers contain mutations at the group a determinant. The mutation frequency at the hotspot codons 40 and 47 is approximately 83%, 1 order of magnitude higher than at the known polymorphic sites of subtype-specific determinants at codons 122 and 160, which is approximately 4%. This new mutational domain is found to coincide with a major histocompatibility complex class I-restricted T-cell epitope. The potential biological significance of this novel mutation in the immunopathogenesis of HBV chronic carriers is discussed.
Adult↗
Routine rapid Mycobacterium species assignment based on species-specific allelic variation in the 65-kilodalton heat shock protein gene (hsp65).
OBJECTIVE: To assess the utility of automated DNA sequencing strategies for Mycobacterium species assignment and surrogate rifampin susceptibility testing of Mycobacterium tuberculosis complex isolates in a hospital-based clinical microbiology laboratory. DESIGN: Consecutive patient specimens (n = 161) cultured in BACTEC 12B medium (growth index of 50 or greater) or on solid media (Löwenstein-Jensen) were analyzed. A 360-bp segment of a gene (hsp65) encoding a 65-kd heat shock protein was sequenced to identify species-specific allelic polymorphism. Identification of sequence variation in the rpoB gene encoding the beta subunit of RNA polymerase was used as a surrogate method to assess rifampin susceptibility in M tuberculosis complex isolates. RESULTS: The automated DNA sequencing strategies rapidly identified virtually all mycobacteria (158 [98%] of 161) to the species level and unambiguously characterized the region of rpoB that contains mutations responsible for rifampin resistance in M tuberculosis strains. With few exceptions, DNA sequence-based species assignment data agreed with diagnostic information obtained by conventional methods. All discrepancies were due to ambiguous biochemical test data or interpretation. The rifampin susceptibility phenotype was correctly predicted for all strains by rpoB sequencing. CONCLUSIONS: Rapid mycobacterial species assignment based on hsp65 sequencing can be routinely performed in a hospital diagnostic microbiology laboratory setting. The method is especially useful for identification of fastidious organisms, such as Mycobacterium genavense. Sequencing of the rifampin-resistance-determining region of rpoB provides a convenient surrogate strategy for predicting rifampin susceptibility in M tuberculosis complex isolates.
Alleles↗
Adenocarcinoma of cervical esophagus arising in aberrant gastric mucosa.
Ectopic gastric epithelium is common in the cervical esophagus. However, complications arising from such tissue are rare. We report an adenocarcinoma arising in ectopic gastric mucosa of the cardiac type in the cervical esophagus of a 60-year-old man.
Adenocarcinoma↗
Antimicrobial activity of a 13 amino acid tryptophan-rich peptide derived from a putative porcine precursor protein of a novel family of antibacterial peptides.
It has long been speculated that porcine cathelin is an N-terminal fragment of a longer precursor protein which possesses antimicrobial activity. In an attempt to find such a precursor, a cDNA clone was recently isolated and sequenced by screening a cDNA library from porcine bone marrow. In order to identify the functional activity of the putative protein encoded by an open reading frame, we have synthesized various lengths of peptides that correspond to the C-terminal region of the protein and examined them for their antimicrobial activities. We found that a 13 amino acid tryptophan-rich region with the sequence of VRRFPWWWPFLRR had strong antimicrobial activity with a wide spectrum. It showed potency against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Staphylococcus epidermidis, Proteus mirabilis, and Streptococcus group D as well as Aspergillus fumigatus. The action of this peptide is bactericidal rather than bacteriostatic and this activity is completely inhibited by 2 mM MgCl2. Our results indicate that the previously identified putative precursor encoded by the isolated cDNA indeed possesses a potent antimicrobial activity and that this 13 amino acid synthetic peptide is considered to be a potentially effective drug against various infectious agents.
Amino Acid Sequence↗
Effect of felbamate on the pharmacokinetics of lamotrigine.
To assess the possible interaction between lamotrigine and felbamate, a double-blind, randomized, placebo-controlled, two-way crossover study was conducted in 21 healthy male volunteers. Volunteers were given lamotrigine (100 mg every 12 hours) and felbamate (1,200 mg every 12 hours) or matching placebo for 10 days during each period of the crossover. After morning administration on day 10, blood samples were obtained over 12 hours for measurement of lamotrigine. Felbamate increased the maximum concentration (Cmax) and and area under the concentration-time curve from time 0 to 12 hours (AUC0-12) of lamotrigine by 13% and 14%, respectively, compared with placebo. The 90% confidence intervals of the log-transformed pharmacokinetic parameters were within the 80-125% bioequivalance limits, however. Felbamate had no significant effect on the urinary excretion of lamotrigine (total), unconjugated lamotrigine, or the N-glucuronide. One volunteer discontinued the study after developing a rash while taking lamotrigine and placebo. All other adverse events were primarily related to the central nervous system and gastrointestinal tract, with a higher incidence reported during coadministration of lamotrigine and felbamate than with placebo. Overall, felbamate appears to have no clinically relevant effects on the pharmacokinetics of lamotrigine.
Adult↗