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Biomedical subjects

A C Shah

Publications and source records attributed to A C Shah.

At least 19 recordsLinked to original sources
PubMed1992

Concurrent radiation therapy, 5-fluorouracil, and cisplatin for stage II, III, and IV, node-negative, squamous cell head and neck cancer. Results and surgical implications.

METHODS: Between 1983 and 1989, 42 patients with Stage II, III, and IV, node-negative, squamous cell head and neck cancer were treated with concurrent 5-fluorouracil, cisplatin, and radiation therapy. Two courses of chemotherapy with 30 Gy of concurrent radiation therapy were to be followed in all patients by definitive surgery and then an additional 30 Gy of radiation therapy and one to two courses of chemotherapy. The patients who achieved a complete response to the initial induction treatment, however, did not undergo surgery. RESULTS: After the completion of all therapy, 41 of the 42 patients (98%) were considered disease-free. Only 4 of these 41 had relapses, for a projected Kaplan-Meier disease-free survival rate of 86%. Treatment failure occurred in no patients with Stage II, 1 of 17 patients with Stage III, and 4 of 14 patients with Stage IV disease. Of the 42 patients, 23 (55%) did not require surgery after achieving a complete response to induction therapy, and only 1 of these 23 patients subsequently had a relapse. CONCLUSIONS: Although the value of adding chemotherapy to conventional treatment remains unproven in squamous cell head and neck cancer, this treatment schedule appears promising in node-negative disease. Randomized trials will be necessary, however, to validate the efficacy of this approach and confirm the suggestion by the authors that surgery can be avoided in most patients with N0 disease.

Aged↗
PubMed1991

Paranasal sinuses: low-dose CT.

While computed tomography (CT) has become an important imaging modality in the evaluation of the paranasal sinuses, the radiation dose remains higher than is necessary. With use of a head phantom and constant kilovolt peak setting, axial and coronal CT scans of the paranasal sinuses were obtained at each of six successively lower milliampere second settings than are commonly used in clinical practice. Although noise, as measured by the standard deviation of the CT numbers, did increase, images were of diagnostic quality even when dose levels were reduced by a factor of 28. In the same incremental manner, the milliampere second settings used in scanning 90 patients were reduced, with no loss of diagnostic quality. The authors discuss the methods of analysis and the advantages of use of lower milliampere second settings at CT scanning of the sinuses.

Humans↗
PubMed1990

Simultaneous versus sequential combined technique therapy for squamous cell head and neck cancer.

Forty-eight patients with locally confined (M0) squamous cell head and neck cancer were prospectively randomized to receive either simultaneous (SIM) or sequential (SEQ) combined technique therapy with a 5-fluorouracil infusion, a cisplatin bolus injection, and radiation therapy. Patients with residual resectable disease underwent surgery after induction therapy, whereas those achieving a complete response to induction did not require surgery. Patients on the two treatment arms were equivalent in all measured variables, including disease extent. Toxicities of the SIM and SEQ arms also were equivalent except for mucositis and the resultant weight loss, which were more severe on the SIM arm (P = 0.002). With a follow-up time ranging from 9 to 41 months, seven of the 24 SIM patients and 14 of the 24 SEQ patients are considered treatment failures. The relapse-free survival is significantly better on the SIM arm (P = 0.03), although an overall survival advantage has not yet been demonstrated (P = 0.13). The achievement of a complete response after induction therapy correlates with both the relapse-free (P = 0.0005) and overall (P = 0.05) survival, and the likelihood of an induction complete response also is significantly better for those treated with the SIM schedule (P = 0.02). Eighteen patients did not require surgery after achieving an induction complete response. Relapse-free survival does not appear to be compromised in this patient subset.

Adult↗
PubMed1990

Long-term results after chemoradiotherapy for locally confined squamous-cell head and neck cancer.

The long-term results after simultaneous chemoradiotherapy in 54 patients with previously untreated or minimally treated, locally confined (M0) squamous-cell carcinoma of the head and neck are presented. Multiple concurrent courses of radiation therapy and chemotherapy with cisplatin and a four-day 5-fluorouracil infusion were given. Twenty-eight patients underwent definitive surgery and 26 were treated without surgical resection. Treatment-associated toxicity was significant, including mucositis, myelosuppression, and a mean 12% loss of initial body weight. Of the 54 patients, 51 were ultimately rendered disease free by this combined modality protocol. With a follow-up ranging from 42-68 months, the projected Kaplan-Meier relapse-free survival for the entire patient cohort is 70%, with all relapses occurring within 17 months of patient entry. The projected Kaplan-Meier relapse-free survival for patients with Stage IV disease is 62%. The durability of these remissions suggests that there is a significant likelihood of cure in all patients with locally confined disease, and justifies comparative trials with standard treatment.

Adult↗
PubMed1990

Intensive respiratory care service. Organisation, orientation, system and future. Our experience of management of 288 cases.

Between Jan. 1983 and Dec. 1986, 288 patients with acute respiratory failure of varied aetiologies were admitted to tetanus and respiratory care ward. One hundred and twenty patients (41.66%) had primary respiratory diseases, 107 (37.15%) of poisoning, 24 (8.3%) had neuromuscular diseases and 37 (12.48%) had miscellaneous disorders. Ventilatory support was given for more than 6 hours to 118 patients. The overall survival was 61.81% and on ventilator 38.13%. The mortality was high with ARDS (100%), miscellaneous (100%) pneumonia with septicaemia (75%) and COAD (54.28%). Patient with COAD had high mortality with acidosis (pH less than 7.1, P less than 0.01), hypotension (systolic BP less than 90 mm of Hg, p less than 0.05) and oliguria (urine out put less than 400 ml/24 hours, p less than 0.05). Organophosphorus compound was the commonest poison (89.75%) and patients who had moderate to severe hypoxia (pO2 less than 60 mm of Hg), hypotension and an interval of more than 4 hours between the consumption of poison and admission (all P less than 0.05) expired; 68.18% expired within the first 72 hours. All the patients with primary neuromuscular paralysis and bronchial asthma survived. Hospital acquired infections (160 patients), retained secretions (108 patients) and hypotension (64 patients) were the commonest complications seen in the 288 patients. Staphylococcus aureus (32.14%) was the commonest organism isolated. Financial constraints, drug shortages and frequent failure of machines were other major problems in the intensive respiratory care unit.

Acute Disease↗
PubMed1989

Six month follow-up of fourteen victims with short-term exposure to chlorine gas.

Fourteen cases, 5 with pre-existing COAD, exposed to up to 30 p.p.m. chlorine gas in an accidental leakage, were followed up clinically, radiologically and by spirometry at 2 weeks, 4 weeks, 8 weeks and 6 months. All the patients were asymptomatic by 2 weeks and did not reveal any radiological abnormality. The FVC, FEV1 and FVC observed/predicted improved at 4 weeks (p less than 0.05, p less than 0.05, p less than 0.01) and the improvement in FEF0.25-0.75 reached statistical significance (p less than 0.05) at 6 months. The mean improvement in FVC was 0.84 l and FEV1 was 0.6 l at 4 weeks. The 5 patients with pre-existing COAD did not show any evidence of additional lung damage. The observations have been consistent with acute tracheobronchitis with trends towards complete recovery.

Adult↗
PubMed1988

Simultaneous radiotherapy and chemotherapy with 5-fluorouracil and cisplatin for locally confined squamous cell head and neck cancer.

Fifty-four patients with previously untreated or minimally treated locally confined (MO) squamous cell carcinoma of the head and neck were treated with chemoradiotherapy employing multiple courses of simultaneous radiation, cisplatin, and a 4-day 5-fluorouracil infusion. Twenty-eight patients subsequently underwent definitive surgery, and 26 were treated without surgical resection. Of the 54 patients, 51 were ultimately rendered disease free by this combined modality protocol. The projected relapse-free survival rate for the entire cohort is 71%, with a median relapse-free survival time greater than 17 months. Thirteen patients who had tumors that were technically operable did not undergo surgery after achieving a complete response to induction chemoradiotherapy. Only 1 of these patients experienced subsequent local failure. Although the treatment-associated mucositis and local failure. Although the treatment-associated mucositis and myelosuppression were significant, this chemoradiotherapeutic protocol offers a significant chance of relapse-free survival for all patients with locally confined disease and merits comparison with more standard treatment approaches.

Adult↗
PubMed1987

Mass transport in dissolution kinetics. I: Convective diffusion to assess the role of fluid viscosity under forced flow conditions.

The quantitative influence of viscosity on dissolution kinetics is assessed under laminar flow conditions by utilizing a convective diffusion model for drug dissolution. Functional dependency of three types of viscosity inducing agents is established with respect to the parameters of fluid flow rate, diffusivity, and solubility. Studies of aqueous solutions of sucrose and of glycerol demonstrate that the decrease in dissolution rate of ethyl p-aminobenzoate is related to the decrease in solute diffusivity in these solutions, whereas the solubility change in the glycerol solutions has an additional independent simultaneous effect. Dissolution in hydroxypropyl cellulose solutions remains constant under fixed fluid flow conditions because of the negligible effect of the polymer upon the drug diffusivity. A change in fluid flow rate, however, alters the dissolution rate and correlates quantitatively with the rate of shear in the convective diffusion model. The interpretation of the effect of viscosity on dissolution kinetics with the convective diffusion model explains these phenomena quantitatively in terms of the fundamental mass transport processes.

Cellulose↗
PubMed1987

Mass transport in dissolution kinetics. II: Convective diffusion to assess role of viscosity under conditions of gravitational flow.

Dissolution kinetics was studied in a laminar flow cell, through which aqueous solutions of increasing viscosity flowed under the force of gravity, in order to help elucidate the mechanism of drug dissolution. The viscosity was varied by addition of either hydroxypropyl cellulose, sucrose, or glycerin. The dissolution data were evaluated quantitatively in terms of a convective diffusion model for dissolution. It was demonstrated that the decrease in dissolution rate of a test compound due to viscosity in the polymer solution occurs primarily because of a decrease in the rate of shear over the dissolving surface. In solutions of sucrose or glycerin, the decrease in dissolution rate due to viscosity results because of a decrease in the diffusivity of the solute in addition to the decreased rate of shear. Also, the model accounts for the increase in solubility in the glycerin solution. Thus, the influence of viscosity on dissolution depends on whether the viscosity-inducing agent primarily affects only the flow properties of the liquid, or whether it affects diffusivity (i.e., a "micro" viscosity effect, in addition to the flow properties).

Cellulose↗
PubMed1987

Evaluation of reversible polymorphic phase transitions by thermal analysis.

Crystalline states of 1,2-dihydro-6-neopentyl-2-oxonicotinic acid, an investigational antidiabetic drug, were evaluated by thermal analyses. Two polymorphs were detected for the drug, Form I (m.p. 193 degrees C) and Form II (m.p. 196 degrees C). Interconversion of the polymorphs upon cyclic solid-melt transitions provided confirmation of the crystal forms. Solidification of the melt was observed to occur either at 162 or 182 degrees C with the formation of Form I or Form II crystals, respectively. Form I underwent partial conversion to Form II upon heating at 10 degrees C min-1 when nucleating crystals of Form II were present in the sample. Differential scanning calorimetry (DSC) thermograms were recorded for different lots of the drug, solvent-recrystallized samples, and a series of known mixtures of Form I and II polymorphs. The study illustrates the usefulness of cyclic heat-cool studies to characterize polymorphic crystal forms of drugs.

Crystallization↗
PubMed1985

Combination chemotherapy prior to definitive local therapy in squamous cell carcinoma of the head and neck.

30 patients with locally advanced squamous cell carcinoma of the head and neck were given chemotherapy with methotrexate, bleomycin and cis-Platinum prior to planned definitive surgery and/or radiation therapy. Chemotherapy was well tolerated and 90% of patients responded. Of 14 initially unresectable patients, 6 became operable after chemotherapy. After definitive therapy 70% of patients were considered complete responders, and 43% of the entire cohort remain disease-free. All partial responders have died. Patients receiving chemotherapy, surgery and radiation had a significantly greater likelihood of achieving a complete response than those receiving chemotherapy and radiation alone. Although this initial chemotherapy is highly active in this disease its contribution to ultimate survival is unclear. Overall treatment success is determined by the results of definitive therapy.

Adult↗
PubMed1978

Bioavailability of acetazolamide tablets.

Plasma acetazolamide levels were measured by an enzymatic assay following single 250-mg oral tablet doses to 20 healthy volunteers; five different lots of acetazolamide tablets from a single manufacturer were used in a balanced incomplete block design. From the measured plasma levels, estimates of the bioavailability parameters (area under the plasma concentration versus time curve, time to peak plasma concentration, and peak plasm concentration) were obtained by least-squares digital computer fitting. No significant differences among the tablets were observed (alpha = 0.05) for the analysis of variance of the area under the curve or time to peak parameters. Two tablets, however, provided statistically higher peak plasma concentrations than the other three. Thus, lot-to-lot bioinequivalence of acetazolamide tablets was observed. Some in vitro tests employed showed general trends for correlation with the in vivo data. However, considerable refinement of these technique appears necessary for in vitro prediction of the observed lot-to-lot bioinequivalence.

Acetazolamide↗
PubMed1977

Application of a convective diffusion model to membrane transport.

Studies were carried out on the permeation rate of butambed through a dimethicone membrane. Under conditions of "aqueous diffusion layer control", the permeation rate was accurately described by a mathematical model based on convective diffusion theory. In accordance with model, the rate of permeation from a saturated donor phase was shown to be equal to the rate of dissolution from a pure solid.

Aminobenzoates↗
PubMed1977

Mechanism of surface lubrication: influence of duration of lubricant-excipient mixing on processing characteristics of powders and properties of compressed tablets.

A mathematical expression for tablet hardness was related to lubricant mixing by considering increases in the surface coverage with prolonged mixing time. The duration of lubricant mixing significantly changed the apparent bulk volume of the mix, ejection force during tableting, hardness, and disintegration and dissolution properties of tablets. These findings may provide some rationale for the changes in processing characteristics and properties of finished drug products often encountered in the scale-up of solid dosage formulations. Several lubrication mechanisms are discussed in connection with the duration of mixing effects and scanning microscopy studies.

Drug Compounding↗
PubMed1975

Convective diffusion model for a transport-controlled dissolution rate process.

A mathematical model based on convective diffusion was developed to describe the rate of dissolution form the surface of a compressed compact. Experimental studies were carried out to test the model. The basic experimental apparatus consisted of a modified rotating-filter-stationary basket dissolution test apparatus. Dissolution rates from rectangular and circular surfaces of an homologous series of p-aminobenzoate esters permitted testing the theory with respect to solubility, geometry, and agitation conditions. The correlation between experimental results and theory was reasonalby good considering that the test conditions were somewhat less than ideal.

Aminobenzoates↗
PubMed1975

Evaluation of a convective diffusion drug dissolution rate model.

A recently introduced drug dissolution rate model based on convective diffusion was evaluated by experimentally determining dissolution rates. Alkyl p-aminobenzoates were used as the test compounds in a dissolution cell which promoted laminar flow of the liquid past the dissolving surface. The parameters evaluated were diffusivity, solubility, rate of shear, dissolving surface shape, and orientation of the surface relative to flow. The agreement between theory and experiment was quite satisfactory with respect to the functional dependence of the rate on these parameters as well as the actual magnitude of the rates.

Aminobenzoates↗