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Biomedical subjects

K K Ang

Publications and source records attributed to K K Ang.

At least 19 recordsLinked to original sources
PubMed1992

Intrinsic radiosensitivity of normal human fibroblasts and lymphocytes after high- and low-dose-rate irradiation.

The existence of heritable radiosensitivity syndromes and clinical observations in radiotherapy patients suggests that human cellular radiosensitivity differs among individuals. We report here an in vitro study of radiosensitivity in 30 fibroblast and 29 lymphocyte cultures obtained from cancer patients and controls. In 25 cases, both fibroblasts and lymphocytes were obtained from the same donors. Fibroblasts were cultured from skin biopsy samples, and peripheral T-cell lymphocytes were cultured from blood. Clonogenic survival assays were performed by using high- and low-dose-rate irradiation; lymphocytes were in G0 phase and fibroblasts in confluent plateau phase. Various end points were calculated and compared (i.e., surviving fraction at 2 Gy, initial slope of the survival curve, and doses resulting in 10 and 1% survival, respectively). Depending on the end point, the coefficient of variation of the survival parameters ranged from 31 to 68% for lymphocytes and 21 to 41% for fibroblasts following high-dose-rate irradiation. Similar ranges were obtained after low-dose-rate irradiation. Variance analysis performed on replicate assays in cultures derived from the same patient showed that variation due to technical or sampling errors was significantly lower than variation between individuals (P = 0.00034 and 0.014 for fibroblasts and lymphocytes, respectively). No correlation was observed between the radiosensitivity of lymphocyte and fibroblast cultures derived from the same donors. We conclude that there is significant variation in normal cell radiosensitivity among individuals. On the other hand, comparisons of lymphocyte and fibroblast radiosensitivities suggest that tissue-specific characteristics, such as differentiation status, may variably modulate radiosensitivity.

Breast Neoplasms↗
PubMed1992

Is the experience with CHART compatible with experimental data? A new model of repair kinetics and computer simulations.

A new incomplete repair model is introduced that differs from previous models of this type by not assuming that repair is complete during long intervals, e.g. "overnight" intervals of 12-24 h. The model was used to assess the risk of myelopathy resulting from continuous hyperfractionated accelerated radiotherapy treatment (CHART) in light of recent experimental data on the rat spinal cord. Model calculations employing biexponential repair kinetics showed that CHART treatments might result in a higher myelopathy risk than an equal dose given in conventional 2-Gy fractions if the parameters obtained from the animal data hold. The probability of observing what has been reported for CHART was determined in computer simulations for different variance scenarios. The chance to observe four myelopathies in the 74 cervical cord patients was estimated to range between 25 and 62%, while the probability to see 0 in 68 thoracic cord patients ranged from 48 to 27%. These numbers were derived from reasonable assumptions about the repair kinetics (e.g. 60% of damage repaired with a half-time of 8 h) so that the over-all probability to observe 4/74 and 0/68 was maximized, and depending on the scenario fell in the range 12-17%. Finally, from these simulations a myelopathy risk of approximately 0.3-1.2% is predicted for the currently employed maximal CHART dose to the spinal cord, i.e. 42 Gy. We conclude that the CHART experience is not compatible with the new experimental data (p < 5%). Incomplete repair is unlikely to be the sole reason for the unexpected toxicity of CHART (p < or = 17%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Impact of spinal cord repair kinetics on the practice of altered fractionation schedules.

The kinetics of repair of sublethal lesions in the spinal cord was assessed in detail using a rodent model. Experiments were designed to obtain the fractionation sensitivity, alpha/beta, and to quantify the kinetics of repair after a clinically relevant fraction size. Pairs of 2-Gy fractions at intervals ranging from 0 to 24 h were given from Monday through Friday, to cumulative doses of 40-84 Gy. In addition, two groups of animals received 1.5 or 1.2 Gy twice a day at 8-h intervals, 5 days a week, to total doses of 66-90 Gy and 67.2-98.4 Gy, respectively. All irradiations were followed by a top-up dose of 16 Gy. Analysis of the experimental data revealed that a bi-exponential repair model fit the experimental data significantly better than did the mono-exponential model (p = 0.002). The repair half times obtained were 0.7 (0.2-1.3) h and 3.8 (2.6-4.9) h, respectively. The proportion of injury repaired by the longer half time was estimated to be 0.62 (0.37-0.86). The data showed that delivering 2 fractions per day at 6- or 8-h intervals instead of one per day led to a 16.5% (11.8-21.1%) and 13.5% (9.1-17.8%) reduction in the tolerance, respectively. Finally, the results indicated that when incomplete repair between fractions was accounted for, the linear-quadratic (LQ) model was valid in describing fractionation response down to 1.2 Gy per fraction.

Animals↗
PubMed1992

Carcinomas of the nasal cavity.

Between 1969 and 1985, 45 patients with carcinomas of the nasal cavity proper received curative treatment. Thirty patients had squamous cell carcinoma, one had undifferentiated carcinoma, 9 had adenocarcinoma, and 5 had adenoid cystic carcinoma. Eighteen patients were treated with definitive radiotherapy (interstitial brachytherapy in 5 and external beam therapy in 13 patients), and 27 received surgery and radiotherapy. The median length of follow-up was 11 years (range: 2.8-16.8 years). Thirty-six patients had no evidence of disease at the last follow-up visit. All 14 patients with carcinoma of the nasal septum had the disease controlled. Nine of 31 patients with lesions of the lateral wall and floor died of the disease, 5 of uncontrolled local disease, 2 of distant metastases, and 2 of both. The disease-specific survival rates at 5 and 10 years were 83 and 80%, respectively, and the corresponding overall survival rates were 75 and 60%, respectively. Blindness occurred in 4 patients, 2 due to orbital exenteration and 2 to radiation injury to the cornea and optic pathway. Other infrequent side effects were bone necrosis, dental decay, nasal stenosis, and septal perforation. This study indicated that the prognosis of patients with nasal cavity carcinoma was better than that of patients with maxillary sinus cancer treated during the same era. In addition, the study showed that carcinomas of the nasal septum were smaller than those of lateral wall and floor at diagnosis, so that excellent control could be achieved by definitive radiotherapy; when accessible, interstitial brachytherapy might be the treatment of choice in such patients.

Adenocarcinoma↗
PubMed1992

Devices valuable in head and neck radiotherapy.

Normal tissue reactions limit the use of radiotherapy in the management of patients with head and neck neoplasms. Customized intraoral stents can help prevent unnecessary irradiation of various normal tissues thus reducing severity of reactions. Two basic types of devices, referred to as shielding and positional stents, are presented. The fabrication and the application of such devices are illustrated through five case reports. Recommendations on use of these tools and the possibility of combining these means with methods to improve dose distribution within the target volume containing air gaps are provided. Close collaboration between the attending radiotherapist and dentist is essential for designing appropriate devices for individual patients. However, when properly designed and used, these stents are effective in reducing treatment morbidity.

Adult↗
PubMed1992

Radiosensitivity measurement of keratinocytes and fibroblasts from radiotherapy patients.

Genetic diversity is believed to influence cellular radiosensitivity and individual variability in normal tissue reactions to radiotherapy. To measure normal cell radiosensitivity in vitro, we investigated a culture technique that yields keratinocyte and fibroblast cell cultures from small skin biopsy samples (average weight 32 mg). This technique uses 3T3 NIH cells as feeder cells, culture medium containing dialyzed fetal calf serum, low calcium, and various growth factors for keratinocyte growth. A calcium concentration of 4 x 10(-3) M and the use of lethally irradiated NIH 3T3 feeder cells were critical to the success of this method. Primary keratinocyte cultures were successfully obtained from nine biopsy specimens, and radiosensitivity measurements were obtained in six of the resulting strains. Keratinocytes were, in general, more radioresistant than fibroblasts derived from the same specimen. We conclude that radiosensitivity assessment of keratinocyte and fibroblast cultures derived from small punch biopsy specimens is feasible. Further studies can now be carried out to determine the degree of variability between individuals and the relationship between in vitro keratinocyte and fibroblast radiosensitivity and their value in predicting normal tissue responses to radiotherapy.

Cell Survival↗
PubMed1992

The relationship between apoptosis and atrophy in the irradiated lacrimal gland.

Atrophy is generally considered to be a true late effect of radiation. However, in serous glands, atrophy was thought to be a consequential late effect because serous cells die within hours of irradiation and the apparent effects of atrophy are observed contemporaneously with radiation treatment. Therefore, to determine the pathogenesis of atrophy in serous glands, it is necessary to differentiate between parenchymal loss as a result of direct radiation death of serous cells and parenchymal loss as a result of serous cell death that is secondary to fibrosis, vascular damage, or precursor cell death. The lacrimal glands of 62 rhesus monkeys have been irradiated to single doses of 2.5 to 20 Gy and examined at intervals of 4 hr to 112 days postirradiation. Serous cells (nuclei) and acini were counted in at least 30 high power fields per (dose, time) point. At each dose and time of sacrifice, the average number of nuclei per acinus and the average number of acini per high power field were calculated. Also at each dose and time, the distribution of the number of nuclei per acinus was examined to determine how the frequency of acinar sizes changed as a function of irradiation. The number of cells per acinus appears to rise initially, but this is likely a result of the degranulated cells being physically smaller, yielding an artificially higher count. Within 4 days after 12.5 Gy, the average number of nuclei per acinus approaches control values and remains within the range of controls for at least 112 days. The number of acini per high power field decreases steadily for 30 days after 12.5 Gy. From 30 to 112 days, there is some recovery of this number, but it remains well below control values. At 24 hr, the number of nuclei per acinus shows a distinct dose response up to 20 Gy. However, at 30 days there is no evidence of a dose response for this parameter. These results indicate that even though serous cells die in significant numbers within hours of irradiation, the atrophy of the lacrimal gland (and by extension, the parotid gland) is a result of the death of the serous stem cell or precursor. Consequently, protection of serous cells from radiation apoptosis will not diminish serous gland atrophy.

Animals↗
PubMed1992

Radiation-induced apoptosis of oligodendrocytes in vitro.

It has been suggested that glial cells and/or their progenitors are the primary target cells for radiation-induced demyelination. Cultures of terminally differentiated oligodendrocytes, immature oligodendrocytes, and O-2A progenitor cells were generated from the cerebral cortex and spinal cord of perinatal rat pups. Irradiation of cultures of terminally differentiated oligodendrocytes resulted in a significant increase in the percentage of apoptotic cells from 15% in control to 30% in irradiated samples, with the maximum increase induced by 10 Gy. This increase in apoptosis could be observed by 1 h after irradiation with the maximum level reached at 3-6 h. Apoptotic cells were not detected before or after irradiation of cultures of O-2A progenitor cells or immature oligodendrocytes. These data suggest that radiation-induced apoptosis of terminally differentiated oligodendrocytes may be involved in early demyelination.

Animals↗
PubMed1992

Neutron RBE for primate spinal cord treated with clinical regimens.

The RBEs of high-energy neutrons given in 9 or 12 fractions for cervical spinal cord injury in rhesus monkeys was determined using photons at 2.2 Gy per fraction as the reference radiation. Because the dose-response functions were not parallel, the RBE was not constant but rather increased with dose or, equivalently, with the probability of myelopathy. This required the development of a novel method of determining the RBE versus level of response. The RBE is presented as a function of probability of myelopathy from 0.1 to 99%. At a 50% incidence of myelopathy, the RBE (+/- 1 SE) was 5.22 +/- 0.15. A difference in the histopathology of lesions induced by photon and neutron treatments was observed.

Animals↗
PubMed1991

Radiation apoptosis of serous acinar cells of salivary and lacrimal glands.

Xerostomia and xerophthalmia are common and potentially serious local side effects of radiotherapy for head and neck cancer. Clinical observations supported by experimental findings show that radiation, even in low doses, causes acute diminutions of saliva and tears by rapidly killing the serous cells of the salivary and lacrimal glands, respectively. Serous acini of salivary and lacrimal glands have similar developmental, morphologic, and functional characteristics. Serous acinar cells are functionally mature, secretory epithelial cells that normally do not divide and are long lived. Irradiation of the salivary and lacrimal glands of rhesus monkeys resulted in selective death of serous acinar cells within 24 hours. The paradigm for acute radiation seroadenosis is intermitotic or interphase cell death caused by apoptosis.

Animals↗
PubMed1991

Prognostic variables in parotid gland cancer.

We performed a retrospective review of 178 previously untreated patients with primary malignant neoplasms of the parotid gland treated at our institution between 1960 and 1985. Patients were followed up for a median of 7.5 years. Fifty-nine percent underwent surgery alone, and 40% underwent surgery and radiation therapy. Univariate and multivariate analyses established the prognostic influence of cancer stage, cancer grade, histologic type, presence of lymphatic invasion, perineural invasion, tumor size, extension beyond the parotid gland fascia, cervical adenopathy, quality of margins, and patient age and gender. Survival was influenced most by tumor grade, tumor size, presence of positive cervical lymph nodes, and facial nerve invasion. The risk of local-regional recurrence was most affected by cervical adenopathy and tumor size. Distant metastases were predicted by tumor grade and size. At last contact, 39% of patients were alive and free of disease, while 26% had died of the disease. We analyzed the optimal surgical procedure and the rationale for the selection of combined treatment.

Adolescent↗
PubMed1991

Maxillary sinus carcinomas: natural history and results of postoperative radiotherapy.

Between 1969 and 1985, 73 patients with maxillary sinus cancers underwent surgical excision and postoperative radiotherapy. The clinical stage distribution by the AJC system was 3T1, 16T2, 32T3, and 22T4. Six patients had palpable lymphadenopathy at diagnosis. Surgery for the primary tumor consisted of partial or radical maxillectomy, and if disease stage indicated it, ipsilateral orbital exenteration. This was followed by radiation treatment delivered through a wedge-pair or three-field technique. All but three patients received 50-60 Gy in 2 Gy fractions to an isodose line defining the target volume. Elective neck irradiation was not routinely given. Clinically involved nodes were treated with definitive radiotherapy (five patients) or combined treatment (one patient). Forty-five patients had no evidence of disease at the last follow-up. The 5-year relapse-free survival for the whole group was 51% The overall local control rate was 78%. Patients with larger tumors, particularly if they also had histological signs of nerve invasion, had a higher recurrence rate than others. The overall nodal recurrence rate without elective neck treatment was 38% for squamous and undifferentiated carcinoma, and only 5% for adenoid cystic carcinomas. Therefore, our current recommendation is to deliver elective nodal irradiation routinely to patients with squamous or undifferentiated carcinoma, except for those who have T1 lesions. Treatment complications were vision impairment, brain and bone necrosis, trismus, hearing loss, and pituitary insufficiency. The incidence of major side effects was determined by disease extent and treatment technique. Many technical refinements were introduced in order to limit the dose to normal tissues in an attempt to reduce the complication rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1991

Acinetobacter peritonitis in patients on CAPD: characteristics and outcome.

Acinetobacter species are pleomorphic nonfermenting aerobic Gram negative bacilli which are important organisms causing peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). We describe the characteristics and outcome of Acinetobacter peritonitis (AP) over an 18 month study period. There were 13 episodes of AP (9 identified as variant anitratus, 1 as variant calcoaceticus, 1 as variant, 1 woffi and 2 unspecified) in 11 patients (7 females and 4 males, mean age +/- SEM, 50.1 +/- 4.2 years), accounting for 14.3% of the total number of episodes of peritonitis. Technique failure accounted for 8 cases of AP. The duration of CAPD before the onset of AP ranged from 2 to 13 months. Three patients had AP one month after a different episode of peritonitis. Treatment was successful with intraperitoneal (IP) gentamicin alone in 9 episodes, oral perfloxacin alone in 2, and combination IP ceftazidime and oral perfloxacin in 1. Nine patients responded to treatment without interruption of CAPD. Two patients who were treated with IP gentamicin alone had second episodes of AP 2 and 4 months after treatment and 1 patient converted to hemodialysis because of bowel adhesions after his second episode of AP. One patient had Candida superinfection after clearance of AP. In conclusion AP is a common cause of peritonitis and can be treated in most cases without interruption of CAPD and catheter removal. The use of oral quinolones may be more convenient and equally effective. Diabetes mellitus and technique failure may be important factors.

Acinetobacter Infections↗
PubMed1991

Apoptosis in irradiated murine tumors.

Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors.

Animals↗
PubMed1990

Regional radiotherapy as adjuvant treatment for head and neck malignant melanoma. Preliminary results.

From 1983 through 1988, 83 patients with high-risk cutaneous malignant melanoma (primary lesion thicker than 1.5 mm or palpable lymphadenopathy) of the head and neck region were enrolled in a study designed to assess the efficacy of a few large doses of radiation (24 to 30 Gy in 4 to 5 fractions). The actuarial 2-year locoregional control rates for the three groups were 95%, 90%, and 83%, respectively. Corresponding survival rates were 80%, 71%, and 69%. The majority of failures were due to distant metastases. Locoregional control rates were better than those reported earlier with surgery alone for comparable patients. The treatment morbidity was minimal.

Adolescent↗
PubMed1990

Radiation myelopathy in primates treated with conventional fractionation.

A rhesus monkey model was used to assay the radiation tolerance of the spinal cord to 60Co radiation given in 2.2 Gy fractions. The D50 was found to be 76.1 Gy (SEM = 1.9 Gy); the estimated doses for 1% and 0.1% myelopathy were 59.1 +/- 5.5 Gy and 52.1 +/- 7.1 Gy, respectively. The latent period ranged from 5 to 20 months and decreased with increasing dose. All symptomatic animals had white-matter parenchymal lesions involving major motor tracts, and most also had vascular lesions in the white matter. Spinal cords of asymptomatic animals had either no histopathologic changes or small white-matter lesions that did not involve motor tracts.

Animals↗
PubMed1990

Primary radiotherapy in the treatment of stage I and II oral tongue cancers: importance of the proportion of therapy delivered with interstitial therapy.

From January 1963 through December 1979, 103 patients with Stage T1N0 and T2N0 squamous cell carcinomas of the oral tongue were treated with definitive radiotherapy. The primary was Stage T1 in 18 patients and T2 in 85 patients. Therapy to the primary consisted of interstitial therapy only in 18 patients, 16-37 Gy in 2.4-4.0 Gy fractions followed by interstitial therapy to doses of 38-55 Gy in 31 patients, external therapy of 40-50 Gy with interstitial therapy of 20-40 Gy in 46 patients, and external beam only to doses of 45-82 Gy in 8 patients. Follow-up ranged from 2 to 290 months (median 159 months). Five of the 8 patients treated with external therapy alone and 6 of the 18 patients treated with interstitial therapy failed at the primary site. In those patients treated with a combination of external and interstitial therapy the 2-year local control rate was 92% for patients treated with external therapy to doses of less than 40 Gy combined with a moderately high dose of brachytherapy, compared with 65% for patients who received external therapy to doses of greater than or equal to 40 Gy with lower brachytherapy doses (p = .01). Conversely the risk of failure in the neck was directly related to the dose delivered by external beam therapy. In field recurrence occurred in 44% of patients receiving no therapy to the neck. 27% in those receiving less than 40 Gy, and 11% in those patients with neck treatment to greater than or equal to 40 Gy. Eleven of 87 (13%) of patients who were at risk for complications for greater than or equal to 24 months developed severe complications; severe complications were more likely to occur in the group who received most of their therapy with external beam irradiation. These data show that a high dose of interstitial therapy is necessary to secure optimum local control of early primary tongue cancer. Because of the high frequency of moderate to severe late complications in this series we have adopted a policy of initial surgery for most oral tongue cancers with postoperative radiotherapy if indicated by pathological features predictive of a high rate of local-regional failure.

Adult↗