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Biomedical subjects

K Ahmad

Publications and source records attributed to K Ahmad.

At least 127 records · Page 7Linked to original sources

Surgical reporting instrument designed to improve outcome data in head and neck cancer trials.

Precise reporting of surgical staging and operative data in multi-institutional protocol studies could provide a number of benefits: 1) fewer cases would be discarded because of inadequate data, 2) staff review time would be reduced, 3) there would be assurance that participating surgeons were performing similar operations on similar tumors, 4) the resulting precision in stratification should improve the likelihood of achieving accurate comparison of the treatment options under study, and 5) by comparing the surgical parameters with local-regional control of disease, the specific factors that have a statistically significant correlation with outcome could be identified. This paper presents a computer-based, anatomically oriented reporting instrument that should improve the reliability of surgical data available to multi-institutional protocols.

Clinical Trials as Topic↗

Short communication on erythrocyte membrane stabilization by decamethonium and succinylcholine.

The effects of decamethonium and succinylcholine on hypotonic haemolysis of erythrocytes were studied. These drugs at concentrations of 5 x 10(-8) M to 10(-4) M caused a dose dependent inhibition of haemolysis of erythrocytes in 0.45 pc NaCl but lysis occurred when the drug concentrations were increased to 10(-3) M. These results indicate that decamethonium and succinylcholine may have a membrane stabilization-lysis effect on erythrocytes.

Decamethonium Compounds↗

Hyperfractionated radiation therapy and bis-chlorethyl nitrosourea in the treatment of malignant glioma--possible advantage observed at 72.0 Gy in 1.2 Gy B.I.D. fractions: report of the Radiation Therapy Oncology Group Protocol 8302.

Between January 1983 and November 1987, the Radiation Therapy Oncology Group conducted a prospective, randomized, multi-institutional, dose searching Phase I/II trial to evaluate hyperfractionated radiation therapy in the treatment of supratentorial malignant glioma. Patients with anaplastic astrocytoma, or glioblastoma multiforme, age 18-70 years with a Karnofsky performance status of 40-100 were stratified according to age, Karnofsky performance status, and histology, and were randomized. Initially randomization was to one of three arms: 64.8 Gy, 72.0 Gy, and 76.8 Gy. Fractions of 1.2 Gy were given twice daily, 5 days per week, with intervals of 4 to 8 hr. All patients received bis-chlorethyl nitrosourea (BCNU) 80 mg/m2 on days 3, 4, 5 of radiation therapy and then every 8 weeks for 1 year. After acceptable rates of acute and late effects were found, the randomization was changed to 81.6 Gy and 72.0 Gy with a weighting of 2:1. Out of 466 patients randomized, 435 were analyzed. The distribution of prognostic factors was comparable among the 76.8 Gy arm, 81.6 Gy arm, and the final randomization of the 72 Gy arm. The 64.8 Gy arm and the initial randomization of the 72 Gy arm had somewhat worse prognostic variables. Late radiation toxicity occurred in 1.3-6.8% of the patients, with a modest increase with increasing radiation dose. The best survival occurred in those patients treated with 72 Gy (median survival of 12.8 months overall, and 14 months for the final 72 Gy randomization). The Cox proportional hazards model confirmed the prognostic variables of age, histology and Karnofsky performance status. In addition, the longer interval of 4.5-8 hr was associated with a worse prognosis than the 4-4.4 hr interval (p = 0.0011). The difference in survival between the 81.6 Gy arm and the lower three arms approached significance (p = 0.078) with inferior survival observed in the 81.6 Gy arm. When therapy was evaluated by radiation therapy dose received (60-74.4 Gy compared with 74.5-84.0 Gy), the p value was 0.062 in favor of the lower dose range. Patients with anaplastic astrocytoma treated with 72 Gy by hyperfractionation + BCNU had at least as good a survival as those treated with 60 Gy by conventional fractionation + BCNU on Radiation Therapy Oncology Group protocols 7401 and 7918. This suggests that 72 Gy delivered by 1.2 Gy twice daily is no more toxic than 60 Gy delivered by conventional fractionation.

Adult↗

Presence and possible role of c-ras and nuclear (c-fos and c-jun) proto-oncogene products in preimplantation embryonic development in mice.

The presence and possible role of products of nuclear (c-fos and c-jun) and c-ras proto-oncogenes were investigated in preimplantation embryonic development in mice. Polyclonal antibodies to c-fos or c-jun proto-oncogene products did not affect development of in vitro-cultured embryos from two-cell to morula or from morula to late blastocyst stages. However, v-H-ras monoclonal antibody (mAb) to c-ras protein (p21), although it did not inhibit the development of in vitro-cultured embryos from two-cell to morula stages, it significantly (P < .001-.005) inhibited the development of morula to late blastocyst stages in a dose-dependent manner. The effects of v-H-ras mAb were specific, since immunoabsorption with synthetic ras peptide completely blocked inhibitory effects of v-H-ras mAb. Neither c-fos nor c-jun antibodies reacted with specific proteins corresponding to c-fos (62 kDa) and c-jun (39 kDa) products on the Western blots of various murine ova/embryos extracts. However, the c-fos and c-jun antibodies reacted with 62 and 39 kDa protein bands, respectively, on the blot of NIH 3T3 cells extract. The v-H-ras mAb specifically identified 21 +/- 3 kDa protein corresponding to c-ras p21 on the blots of early as well as late blastocyst extracts. The rat control ascites IgG1 did not react with any protein band on the blots of various ova/embryo extracts. The reactions of v-H-ras mAb on the Western blots of blastocyst extracts were specific, since immunoabsorbed antibody was unable to react with any specific band on blots of early or late blastocyst extract. These results were further confirmed by immunoprecipitation procedure utilizing v-H-ras mAb. Again, the v-H-ras mAb immunoprecipitated a 21 kDa band from early as well as late blastocyst extracts. The rat control ascites IgG1 did not react with any band corresponding to p21 in the immunoprecipitation procedure. These results suggest that the specific products of nuclear proto-oncogenes, the c-fos and c-jun, are not detected in murine ova and preimplantation embryos, and the respective antibodies do not inhibit embryogenesis, indicating that they may not play a major role in early embryonic development. On the other hand, the product of c-ras proto-oncogene is specifically expressed in the blastocyst-stage embryos and may have a possible role in preimplantation embryonic development in mice.

3T3 Cells↗

Studies on neurolathyrism.

Neurolathyrism is a neurological condition seen among people who eat the seeds of Lathyrus sativus (LS) as a principal source of food energy for 2 months or more. It is characterized by severe muscular rigidity and paralysis of the lower limbs. beta-N-Oxalyl-L-alpha,beta-diaminopropionic acid is the principal toxin found in the seed. No experimental animal model for neurolathyrism could be produced by feeding either the seeds or the toxin, although the condition has been known for centuries. We discovered that experimental neurolathyrism could be produced in guinea pigs and primates that needed an external supply of ascorbic acid by making them subclinically deficient in ascorbic acid and feeding them the seeds of LS or extracts thereof. Autoclaving the seeds of LS with lime removes the toxin.

Animals↗

Involvement of cyclins and cdc2 serine/threonine protein kinase in human sperm cell function.

The presence and roles of mitotic cyclins (cyclin A and cyclin B1), and cdc2 and related (having an N-terminal PSTAIRE conserved sequence) serine/threonine protein kinases were investigated by use of specific antibodies. The cyclin A and cyclin B1 antibodies reacted specifically with the acrosomal regions of human sperm cells in the indirect immunofluorescence technique (IFT) and recognized the specific band of p60 (cyclin A) and p62 (cyclin B1) on the Western blot of sodium deoxycholate (DOC)-solubilized noncapacitated human sperm preparation. Both antibodies reacted more strongly with the specific cell region/band of capacitated sperm than with that of noncapacitated sperm. The cdc2 and PSTAIRE antibodies also reacted predominantly with the acrosomal regions of human sperm cells in IFT and recognized the specific band of 34 kDa corresponding to p34 cdc2 protein on the Western blot of DOC-solubilized noncapacitated human sperm preparation. Again, both antibodies reacted more strongly with the specific cell region/band of capacitated sperm than with that of noncapacitated sperm. The cyclin A antibodies (but not the cyclin B1 antibodies) and cdc2 antibodies as well as the PSTAIRE antibodies significantly (p = 0.02 to p < 0.001) increased (rather than decreased) the human sperm penetration rates of zona-free hamster ova; the cyclin A and cdc2 antibodies showed the strongest enhancing effects. These three antibodies significantly increased the acrosome reaction and release of acrosin activity from the sperm cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗

Antiidiotypic antibodies to sperm in sera of fertile women that neutralize antisperm antibodies.

The presence of antiidiotypic antibodies (ab-2) to sperm was investigated in the sera of fertile, infertile, and virgin women using sperm-specific anti-FA-1 monoclonal antibody Fab'.ab-2 were detected in 71% (17/24) of sera from fertile women and in none (0/12) of the sera from virgin females by the enzyme-linked immunosorbent assay, Western blot procedure, and immunoprecipitation procedure. Sera from infertile women that had antisperm antibodies showed a minimal presence of ab-2, with only three sera (13%, 3/23) demonstrating the presence of low levels of ab-2. The ab-2 present in fertile women were capable of neutralizing the fertilization-inhibitory activity of anti-FA-1 antibody in a concentration-dependent manner in a human sperm penetration assay (SPA) of zona-free hamster oocytes. ab-2 were also capable of inhibiting the binding of antisperm antibodies to the sperm surface as determined by the immunobead binding technique. This is the first report demonstrating the presence of ab-2 in the sera of fertile women that are capable of neutralizing antisperm antibodies present in sera of infertile women. These findings suggest that the inability to detect antisperm antibody activity in the sera of fertile women may be due to higher levels of ab-2 present in these sera than levels found in sera of infertile women, although both groups may be producing antisperm antibody response after sexual exposure to sperm.

Adult↗

Implications of positive surgical margins.

The recently concluded Head and Neck Intergroup trial tested the addition of three courses of cis-platinum containing chemotherapy to standard treatment of surgery and postoperative radiotherapy for patients with advanced operable squamous cell carcinoma of the head and neck. Only patients with negative surgical margins were eligible for the trial. One hundred twelve patients with positive surgical margins were dropped from the trial but continued to be followed. These patients received a variety of treatments. Positive surgical margins were most often seen in nonglottic primaries and with increasing frequency as the N stage increased. Patients with positive margins who achieved a complete clinical response to subsequent treatment had a median survival of 33.8 months vs. 9.1 months for those with less than a complete clinical response. The addition of chemotherapy did not significantly alter the median survival of the positive margin patients.

Adult↗

Presence of expression products of c-erbB-1 and c-erbB-2/HER2 genes on mammalian sperm cell, and effects of their regulation on fertilization.

The present study was conducted to investigate the presence of expression products of c-erbB-1 and c-erbB-2/HER2 genes on mammalian sperm cell, and study the effects of their antibodies on fertilization. The mature sperm cells from various mammalian species (human, mouse, rabbit and rat) were found to have EGF-receptors but not the p185HER2 molecules by indirect immunofluorescence technique (IFT) and Western blot procedure. Though the EGF-receptors present on sperm cells were functionally active and responded to ligand binding, their activation by EGF or blocking by antibodies did not affect the sperm cells in acquiring their fertilization potential. These results indicate that the products of c-erbB-1 and c-erbB-2/HER2 genes, though they have been shown to have tyrosine kinase enzyme activity, do not seem to play a major role in the development of the fertilizing capacity of sperm cells.

Amino Acid Sequence↗

Neutron therapy in Saudi Arabia: an overview and results of dose searching study in head and neck cancer.

The King Faisal Specialist Hospital and Research Centre is the only center in the Middle East that incorporates a neutron therapy facility. The neutron beam is produced by a cyclotron, which produces a beam by either a (d(15)+Be) or (p(26)+Be) reaction. The beam from the proton reaction is selected for therapy because of its superior physical characteristics. These were verified by an intercomparison conducted by the European Organization for Research on Treatment of Cancer (EORTC) Heavy Particle Therapy Group. Full beam data are presented. The first study in the neutron therapy Program is on the treatment of squamous cancers of the head and neck. This consists of two parts. Part I is a dose searching phase and Part II is a comparison of our current photon treatment versus neutrons using the neutron dose selected by Part I of the study. Results of the dose searching phase (Part I) are presented.

Carcinoma, Squamous Cell↗

Total nodal radiation in progressive sarcoidosis. Case report.

The subject of this article is a patient with sarcoidosis with neurological involvement, who failed to respond to high dose steroid therapy and cyclophosphamide. Low doses (20 Gy) of total nodal and craniospinal irradiation resulted in an excellent response, the patient being alive and in good health 3 years after irradiation without any further steroid therapy.

Adult↗

Expression and function of ras proto-oncogene proteins in human sperm cells.

The presence and role of c-ras proteins were investigated in mature human sperm cells. The v-H-ras monoclonal antibody (mAb) against the c-ras protein, p21, reacted specifically with the acrosomal region of methanol-fixed as well as unfixed-live capacitated and non-capacitated human sperm cell in the indirect immunofluorescence technique. The v-H-ras mAb predominantly recognized c-ras protein of 21 kDa on the Western blot of lithium diiodosalicylate (LIS)-solubilized human sperm preparation. The incubation of sperm cells with v-H-ras mAb affected the sperm cell function in the human sperm penetration assay. The antibody significantly reduced the acrosome reaction and release of acrosin activity from the sperm cells. There was no effect of the mAb on percentage motility, although the mAb significantly affected various motility characteristics such as linearity, amplitude of lateral head displacement (ALH) and beat frequency, the motility parameters involved in the hyperactivation phenomenon of sperm cells leading to capacitation and acrosome reaction. These results suggest that the c-ras or c-ras-like proteins are present in mature sperm cell and may have a role in capacitation and/or acrosome reaction of human sperm cell.

Acrosin↗

The effect of head and neck cancer treatment on whole salivary flow.

The effects of multimodality therapy for head and neck cancer on whole salivary flow were evaluated. Eighteen subjects with head and neck cancer were studied. Resting and stimulated whole salivary flow rates were recorded, pretreatment, after individual modality therapy, and posttreatment. Twenty-four subjects with no history of head and neck cancer matched for age, and sex distribution, served as controls. Primary site, stage, major salivary glands resected, radiation fields, and dose to major salivary glands are reported. The average salivary flow rates for 18 subjects following treatment was reduced 83% for resting and 86% for stimulated saliva from pretreatment levels. The null hypothesis that the overall resting and stimulated whole salivary flow rates are unaffected by treatment (surgery and radiation) of the head and neck cancer was rejected (P values at 0.05 level of significance). Stage and location of primary, total dose delivered to and volume of gland exposure are important factors when predicting xerostomia following multimodality therapy.

Adult↗

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult↗

High-dose-rate afterloading brachytherapy, external radiation therapy, and combination chemotherapy in poor-prognosis cancer of the cervix.

Fourteen patients with poor-prognosis cervical cancer were treated with concurrent chemotherapy (cisplatin and mitomycin-C), external radiation therapy (RT), and high-dose-rate (HDR) brachytherapy. Pelvic RT was delivered as (a) external-beam radiation (four-field box technique, 40.0 Gy), (b) brachytherapy using HDR 60Co or 192Ir (3.80 Gy/fraction, thrice weekly; total dose, 46.83 Gy) with intrauterine stent, and (c) parametrial boost using an AP field with custom-fabricated step wedges. Post-radical-hysterectomy patients received 50.40 Gy external RT and 3.23 Gy/day vaginal cylinder HDR at 1/2-cm depth (total dose, 16.15 Gy). Complete clinical and radiographic response was noted in all evaluable patients who are alive with no evidence of disease, 3 to 27 months after completion of therapy (median, 9 months). Toxicity consisted of grade 2 to 3 hematologic toxicity (4 patients) and nausea and vomiting in all, but grade 3 in only 2 patients. One patient had grade 2 diarrhea. The only major complication (small bowel obstruction) occurred in a patient with lupus vasculitis. This pilot study demonstrates the feasibility of this regimen in an outpatient setting with acceptable toxicity. More prolonged follow-up of our patients is required to determine its impact on long-term survival.

Antineoplastic Combined Chemotherapy Protocols↗

Eye metastasis from carcinoma of the breast: diagnosis, radiation treatment and results.

The experience at the Gershenson Radiation Oncology Center of 32 cases of metastases to the eye or orbit from breast cancer are presented with a review of the literature. The 32 patients were referred for radiation therapy in the period of 1980-1991. Eighteen patients had metastasis to the choroid, 2 patients had involvement of other parts of the eye (anterior chamber +/- choroid), and 11 patients had orbital metastasis. In one patient, the diffuse nature of the disease prevents subsite assignment. Ten of the patients with eye metastases also had brain or meningeal metastases (8 patients concurrent with eye metastases). Four of the 32 patients had bilateral choroidal metastases. A complete course of radiation therapy was delivered to 28 patients, one patient was not treated and 3 patients received only partial treatment because of general deterioration due to other widespread metastases from breast cancer. Of 21 evaluable patients, 15 had definite improvement. There was no progression of the eye metastases in the other 6 patients. The rest (7 patients) were lost to detailed follow-up of the response of the eye metastases. Four patients are still alive without any severe long-term side-effects. The diagnosis, treatment and outcome is presented with a review of the literature. The importance of emergency treatment for rapidly progressing lesions is stressed as well as the need for detailed treatment planning, careful delivery of daily treatments with a high degree of reproducibility and precision to prevent possible damage to sensitive normal structures.

Adult↗

Initial experience with a practical hyperfractionated accelerated radiotherapy regimen.

This paper presents early results of a trial of a three-fractions-per-day (TID) regimen that is more convenient to schedule than the Continuous Hyperfractionated Accelerated Radiotherapy (CHART) protocol currently being tested in Europe. The treatment schedule used in the CHART regimen has been modified from 36 fractions of 1.5 Gy TID in 12 days to 72 fractions of 1.1 Gy in 24 treatment days, with all fractions delivered during normal working hours. With no weekend treatments, the entire course of radiotherapy is completed in less than 5 weeks. The doses used were determined using the L-Q model, with correction for incomplete repair between fractions and for accelerated repopulation of cancer cells. Comparison with historical controls shows statistically significant improvements both in CR rates for the primary tumor and in acute toxicity, as measured by reduced treatment interruptions. L-Q model calculations predict that, compared to the highest dose achieved in previous studies without exceeding tolerance, we are able to obtain a 12% increase in bioeffect dose to the primary tumor due to accelerating the treatment. An analysis of the potential tumoricidal effectiveness of this new treatment regimen shows that it should be better than several other accelerated fractionation schedules being tested for all values of Tpot. For short Tpot times, the advantage may be as much as one log cell kill, corresponding to a 10-15% potential improvement in local control.

Aged↗

Presence and role of c-myc proto-oncogene product in mammalian sperm cell function.

The presence and role of c-myc protein was investigated in mature sperm cells of the human, mouse, and rabbit. The monoclonal antibodies against c-myc protein (c-myc) reacted with the acrosomal region of the sperm of these mammalian species in the indirect immunofluorescence technique. The c-myc monoclonal antibody (MCA) recognized c-myc protein of 62 and 64 kDa on Western blots of lithium diiodosalicylate-solubilized sperm preparations of these species. The c-myc MCA showed a dose-dependent inhibition of human sperm penetration of zona-free hamster eggs, inhibition of murine in vitro fertilization, and reduced in vivo fertilization in rabbits. There was no effect of the antibody on percent sperm motility, though the antibody significantly affected various motility characteristics such as mean and maximum amplitude of lateral head displacement and curvilinear velocity involved in hyperactivation phenomenon of human sperm cells. These results suggest that c-myc or c-myc-like protein is present in mature sperm cells and may have a role in sperm cell function especially in capacitation and/or acrosome reaction.

Animals↗