Biomedical subjects

K J Stelzer

Publications and source records attributed to K J Stelzer.

At least 37 records · Page 2Linked to original sources

PubMed1994

Stereotactic radiosurgery: a review and comparison of methods.

PURPOSE: Stereotactic radiosurgery (SRS) is an evolving modality for treating well-circumscribed intracranial lesions. Different physical methods have been developed to deliver highly localized dose distributions accurately. We review the different methods and the documented clinical results to present a coherent view of radiosurgery, and to aid physicians and physicists in the appropriate use of this modality. DESIGN: A review of the medical physics and clinical literature was conducted. The physical aspects of the different methods and their impact on treatment were summarized. Results were compiled from those individual clinical series with adequate follow-up data to compare the various modalities with respect to treatment outcome for benign tumors, metastases, and vascular malformations. RESULTS: The physical accuracy was comparable between radiosurgical methods. Differences between gamma radiation and linear accelerator methods had little effect on the dose distribution for single isocenter treatments. Charged particle methods could produce better dose localization for large lesions (> 25 cm3) than was possible with photon methods. Clinical results indicate similar lesion control rates between all radiosurgical methods. There was a progressive increase in the median size of treated lesions for gamma radiation, linear accelerator, and charged particle methods. CONCLUSION: For small lesions (< 5 cm3), physical dose distributions are similar for the photon methods, but linear accelerator methods offer more flexibility for the treatment of intermediate-sized (5 to 25 cm3) lesions in applying future technical developments. More clinical results are needed before firm conclusions can be drawn on the type of lesions to be treated, and the dose-volume parameters to be used.

Brain Neoplasms↗

PubMed1994

Runaway pacemaker during high-energy neutron radiation therapy.

Runaway pacemaker occurred in a patient undergoing high-energy neutron radiation therapy despite adherence to published safety guidelines. The very low estimated dose of 0.9 Gy received by the pacemaker demonstrates the extreme sensitivity of integrated circuits to this new modality of radiation therapy.

Adenocarcinoma↗

PubMed1994

Fast neutron radiotherapy. The University of Washington experience.

An overview of the University of Washington neutron radiotherapy facility is presented. The utility of the multi-leaf, programmable, variable collimator is emphasized. Due to success in the treatment of salivary gland tumors, such patients comprise an ever increasing portion of the patients being treated. A cooperative randomized clinical trial for the treatment of salivary gland tumors was undertaken comparing fast neutrons against photon/electron radiation. At ten years, there was a statistically significant improvement in local/regional control for the neutron group (56% vs 25%, p = 0.009), but there was no improvement in survival (15% vs 25%, p = n.s.). Distant metastases were the primary reason for the failure of improved local/regional control to impact survival in the neutron group. The University of Washington experience is summarized with special emphasis on the treatment of adenoid cystic carcinomas. Excellent local/regional control can be achieved with neutrons even for large tumors arising in the paranasal sinuses. We conclude that the potential morbidity of a surgical debulking procedure is not warranted in most clinical situations.

Adult↗

PubMed1994

Fast neutron radiation therapy. Results of phase III randomized trials in head and neck, lung, and prostate cancers.

The results of phase III trials comparing neutrons to photons for head and neck squamous cell cancers, non-small cell lung cancers, and prostate adenocarcinomas are reviewed, with emphasis given to the most recent U.S. National Cancer Institute sponsored randomized clinical studies in which fast neutrons were delivered using modern, hospital-based, high-energy, isocentric-capable cyclotrons. In locally advanced squamous cell head and neck cancers, neutrons showed no convincing advantage over photons. Fast neutron radiotherapy may have provided a therapeutic benefit in selected patients with inoperable non-small cell lung cancers. For locally advanced prostate adenocarcinomas, neutron therapy resulted in significantly superior clinical and histological loco-regional tumor control, which may translate to improved survival with additional follow-up. In general, severe late complications were more frequent with neutrons, especially in patients treated on older physics laboratory-based equipment. Even with modern state-of-the-art neutron generators, careful beam collimation and treatment planning are required to minimize side effects.

Adenocarcinoma↗

PubMed1994

Common emergencies in cancer medicine: infectious and treatment-related syndromes, Part I.

This two-part article, the last in a series of articles on cancer emergencies, summarizes the common medical emergencies that can occur as a result of infectious processes (Part I) and antitumor treatment secondary to chemotherapy, biological response modifiers, or radiotherapy (Part II). The use of high-dose cytotoxic agents, coupled with the common instillation of indwelling central venous access devices, have altered the spectrum of infectious etiologies that are appreciated in clinical practice. In addition, a myriad of cytotoxic agents and radiotherapeutic treatment schemes are used widely in clinical oncologic practice. While most of their related side effects are not considered life-threatening emergencies, they can be fatal if not recognized early and treated promptly. Moreover, some of these infectious and treatment-related sequelae can be prevented.

Antineoplastic Agents↗

PubMed1994

Common emergencies in cancer medicine: infectious and treatment-related syndromes, Part II.

This article completes a summary of the common medical emergencies that can occur as a result of infectious processes (Part I) and antitumor treatment secondary to chemotherapy, biological response modifiers, or radiotherapy (Part II). The use of high-dose cytotoxic agents, coupled with the common instillation of indwelling central venous access devices, have altered the spectrum of infectious etiologies that are appreciated in clinical practice. In addition, a myriad of cytotoxic agents and radiotherapeutic treatment schemes are used widely in clinical oncologic practice. While most of their related side effects are not considered life-threatening emergencies, they can be fatal if not recognized early and treated promptly. Moreover, some of these infectious and treatment-related sequelae can be prevented. This article highlights some of these clinical observations.

Antineoplastic Agents↗

PubMed1993

A randomized prospective trial of radiation therapy for AIDS-associated Kaposi's sarcoma.

PURPOSE: The optimal dose of radiation in the treatment of AIDS-associated Kaposi's sarcoma has been controversial based on previous nonrandomized retrospective studies. METHODS AND MATERIALS: Seventy-one cutaneous AIDS-associated Kaposi's sarcoma lesions were randomly assigned to 1 of 3 radiation dose regimens--8 Gy in 1 fraction, 20 Gy in 10 fractions, and 40 Gy in 20 fractions. Lesions were measured prior to and following treatment. Complete resolution of palpable tumor was considered a complete response, regardless of residual purple pigmentation. Reduction in palpable tumor to less than 50% of pretreatment area was considered an objective response. Less than 50% reduction in tumor size was considered a nonresponse. RESULTS: Complete response was higher (p = .04) with 40 Gy (83%) and 20 Gy (79%) than with 8 Gy (50%). Absence of residual purple pigmentation was greater (p = .005) with 40 Gy (43%) than with 20 Gy (8%) or 8 Gy (8%). Lesion failure was lower (p = .03) with 40 Gy (52%) than with 20 Gy (67%) or 8 Gy (88%). Median time to failure was 43 weeks with 40 Gy, 26 weeks with 20 Gy, and 13 weeks with 8 Gy (p = .003). CONCLUSION: Fractionated radiotherapy to higher total doses resulted in improved response and control of cutaneous Kaposi's sarcoma. This dose-dependence should be considered in determining the optimal radiotherapeutic regimen for individual patients treated for epidemic Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Femoral vessel depth and the implications for groin node radiation.

PURPOSE: To quantify, based on pretreatment computer tomographic measurements, potential groin node depths, which will aid in optimal treatment planning for patients requiring groin node radiation. METHODS AND MATERIALS: The pretreatment computer tomographic scans of 50 gynecologic cancer patients were reviewed to determine the distance of each femoral vessel beneath the overlying skin surface, as an indicator of potential groin node depth. Correlative data regarding height and weight were obtained from patient medical records, and were used to calculate the Quetelet index, defined as (weight in kg)/(height in m)2. Treatment parameters of 5 patients who failed prophylactic groin radiation in a recently published study were assessed to determine if underdosage represented a possible cause of failure. RESULTS: Individual femoral vessel depths ranged from 2.0 to 18.5 cm. When the depths of all four femoral vessels were averaged in each patient, the mean "4-vessel average" depth for this patient population was 6.1 cm. The median Quetelet index for the group was 25.6, and there was a strong correlation between femoral vessel depth and patient Quetelet index. Recalculation of doses provided to the 5 patients failing prophylactic groin radiation in the Gynecologic Oncology Group study showed that all had received potential tumor doses < 4700 cGy, with 3 patients being underdosed by > 30%. CONCLUSION: While surgery is often indicated in the management of patients with potential groin node metastases, the role of prophylactic groin radiation should not be rejected. Data from this study may aid in the optimal design and implementation of groin node radiotherapy.

Adult↗

PubMed1993

Combined radiotherapy and chemotherapy in the management of local-regionally advanced vulvar cancer.

PURPOSE: To determine, in a retrospective single institutional study, the role of concurrent radiotherapy and chemotherapy in the treatment of local-regionally advanced vulvar cancer. METHODS AND MATERIALS: From 1984 to 1991, 20 patients with locally extensive primary or recurrent carcinoma of the vulva were treated with initial combined radiotherapy and chemotherapy. Seven patients had Federation Internationale de Gynecologie et d'Obstretrique Stage III disease, 10 had Stage IV disease, and three were treated for recurrent disease. None of these patients were considered candidates for primary radical vulvectomy and groin node dissection. Median radiation doses to regions of microscopic disease and gross tumor were 40 Gy (range 30-54 Gy) and 54 Gy (34-70.4 Gy), respectively. All patients received 2 or 3 cycles of 5-Fluorouracil concurrently with radiotherapy. In addition, five patients received Cis-platinum, and one Mitomycin-C. Median at-risk follow-up interval was 37 months. RESULTS: Ten patients had complete resolution of tumor to initial chemoradiotherapy, and eight of these have remained free of tumor relapse. Eight other patients had partial responses, with tumor bulk reduced by > 50%, while the remaining two patients had local-regionally progressive disease. Six of the patients with partial responses had residual tumor successfully resected, although four subsequently recurred. For the entire group of 20 patients, the actuarial 3- and 5-year local control rates were 48% each, and the corresponding disease-specific survival rates were 59% and 49%. There was a suggestion that better local control was obtained in patients who received gross tumor radiation doses > or = 50 Gy. Skin reaction was the major acute toxicity and responded well to conservative management. Long-term sequalae were limited to skin and subcutaneous atrophy. CONCLUSION: These results indicate that initial combined radiotherapy and chemotherapy is effective in the management of advanced vulvar cancer.

Adenocarcinoma↗

PubMed1993

Radiation recall skin toxicity with bleomycin in a patient with Kaposi sarcoma related to acquired immune deficiency syndrome.

BACKGROUND: Radiation recall is a recurrence of acute toxicity within a previously quiescent radiation field that occurs with subsequent administration of chemotherapy. METHODS: A patient with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma (KS) who had radiation recall is reported. The patient was participating in a randomized prospective trial of radiation treatment regimens for KS. Each lesion was randomized to one of three possible radiation fractionation schemes. All lesions were photographed and measured before treatment with radiation. RESULTS: Two skin sites developed erythema and dry desquamation 18 days after completion of radiation therapy to a dose of 40 Gy in 20 fractions. These reactions took place after the second dose of bleomycin administered intravenously on a weekly basis. The reactions were exacerbated by oral etoposide therapy, which was started 4 days after the recall phenomenon was noted. Other cutaneous sites treated with 8 Gy in a single fraction and 20 Gy in ten fractions during the same time period showed no sign of recall skin toxicity. CONCLUSIONS: The authors believe this to be the first report of radiation recall toxicity after bleomycin therapy and of a radiation dose response related to this phenomenon. The potential for radiation recall toxicity should be considered in treatment decisions pertaining to patients with AIDS-associated KS.

AIDS-Related Opportunistic Infections↗

PubMed1988

Interactions of pyrethroids with gramicidin-containing liposomal membranes.

Fluorescence steady-state anisotropy and phase-modulation lifetime techniques have been utilized to study the interactions of pyrethroid compounds with fluid-phase phosphatidylcholine membranes containing the polypeptide gramicidin. This polypeptide is considered to be a model of hydrophobic regions of cellular integral membrane proteins. The pyrethroids disorder lipid packing in cellular membranes and gel-phase liposomes but do not disorder lipid packing in fluid-phase lipid (Stelzer, K.J. and Gordon, M.A. (1984) J. Immunopharmacol. 6, 381-410; (1985) Biochim. Biophys. Acta 812, 361-368) Irrespective of liposomal size, gramicidin incorporation resulted in a substantial increase in anisotropy of the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), in fluid phase lipid. In the absence of gramicidin, permethrin and three other pyrethroids, allethrin, cypermethrin and fenpropathrin, increased DPH anisotropy. In these fluid phase systems, as the protein:lipid ratio was increased, the extent of the pyrethroid-mediated increase in fluorescence anisotropy diminished. Also, the pyrethroids shortened DPH fluorescence lifetimes. At high gramicidin:lipid ratios, permethrin substantially lowered anisotropy in the fluid phase lipid, relative to controls. The data suggest that pyrethroids disturb fluid-phase lipids which have been promoted to a relative state of order by proximity to an integral membrane protein. This type of order is one which is represented by DPH fluorescence anisotropy. A model based on these results is proposed to explain the effects of pyrethroids on lipid packing order in cellular membranes, as determined by DPH fluorescence anisotropy.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1986

Application of constrained regularization analysis to low-angle quasi-elastic light scattering.

A constrained regularization procedure has been applied to a low-angle quasi-elastic light scattering system in order to determine particle size distributions. The conditions under which this procedure may be successfully applied to low-angle photon correlation spectroscopy have been characterized. Acquisition of photon count data over a short time period, relative to the long exponential decay constants of correlation functions obtained at low forward angles, resulted in particle size distributions which were stable with regard to peak width and weighted mean particle radius. Irrespective of the number of photon counts obtained, peak resolution and position on the particle size scale were not optimized unless anomalies in the correlation function due to transient increases in the mean photon counting rate were removed from the photon count data prior to autocorrelation. When such measures were taken, reasonable size distributions were obtained for well characterized protein standards and for liposomal suspensions.

Light↗

PubMed1986

Effect of alterations in lipid packing order by hydrophobic solutes on the association state of protein assemblies in model membranes.

The effects of two hydrophobic solutes which perturb lipid packing order, permethrin and allethrin, on the aggregated state of a lipid membrane-incorporated protein, bacteriorhodopsin (BR), have been determined by resonance energy transfer measurements. As temperature is increased from well below the main gel-fluid phase transition temperature (Tc) of the lipid, patches of aggregated BR dissociate into monomers, a few degrees below the Tc (M.P. Heyn, A. Blume, M. Rehorek and N.A. Dencher, Biochemistry 20 (1981) 7109; M.P. Heyn, R.J. Cherry and N.A. Dencher, Biochemistry 20 (1981) 840). Permethrin and allethrin were found to cause a decrease in the temperature of BR disaggregation which was associated with a decrease in the Tc of the lipid. In gel phase dipalmitoylphosphatidylcholine at 25 degrees C, the pertubing effects of permethrin on lipid packing order were associated with a decrease in the average patch radius from 123 to 33 A. It is concluded that perturbation of lipid packing order by small hydrophobic molecules may alter the stability of protein assemblies in membranes.

Bacteriorhodopsins↗

PubMed1985

Interactions of pyrethroids with phosphatidylcholine liposomal membranes.

Interactions of several pyrethroids with membrane lipids in the form of dipalmitoylphosphatidylcholine (DPPC) liposomes have been studied using fluorescent membrane probes. Fluorescence anisotropy values and lifetimes (determined by phase-shift and demodulation techniques) of the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene, were decreased in gel phase liposomes by pyrethroids at concentrations on the order of 10 microM. The pyrethroids containing a cyano substituent were also observed to cause collisional quenching of diphenylhexatriene fluorescence. Pyrethroids differed in their effectiveness at lowering the phase transition temperature of DPPC, and in their ability to broaden the temperature range of this transition. The fluorescence intensity of DPPC-incorporated chlorophyll a was used to monitor the pretransition of DPPC and the lateral diffusion of a membrane component located in the polar headgroup region. Permethrin did not affect chlorophyll a fluorescence intensity at any temperature. It may be concluded from these results that pyrethroids are preferentially located in the interior hydrophobic regions of the lipid bilayer, and that these compounds can disorder hydrocarbon packing in the bilayer core. However, polar headgroups were not disordered, and diffusion of membrane components in the polar headgroup region was not altered.

Allethrins↗

PubMed1985

Interactions of pyrethroids with phosphatidylcholine bilayers: comparisons in liposomal systems exhibiting large or small radii of curvature.

Pyrethroid interactions with dipalmitoyl phosphatidylcholine (DPPC) vesicles have been characterized in bilayers having large and small radii of curvature. The abilities of pyrethroids to alter the gel-fluid phase transition profiles were determined by steady state fluorescence anisotropy and phase-modulation lifetime techniques using the fluorescent probes cis- and trans-parinaric acid. Using the geometric isomers of parinaric acid as membrane probes, pyrethroids were found to lower the phase transition temperature (Tc) of DPPC large multilamellar vesicles with the same order of comparative effectiveness as previously reported using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Permethrin had a greater depressive effect upon the Tc of DPPC in the small unilamellar vesicle (SUV) system than in the large multilamellar system. Conversely, allethrin was less effective in reducing the Tc of DPPC SUVs. The enhanced effect of permethrin in decreasing the Tc of DPPC SUVs was greatest in regions of more rigid lipid packing, as determined by trans-parinaric acid fluorescence parameters. The results indicate that changes in lipid packing configuration caused by differing bilayer radii of curvature may alter the interactive characteristics of pyrethroids with lipid membranes.

Diphenylhexatriene↗

PubMed1985

Effect of cobalt on biliary excretion of bilirubin and glutathione.

Adult male rats received cobaltous chloride (250 mumol/kg, sc) at various times (1-72 h) prior to assessment of hepatic heme oxygenase activity, bile flow, biliary concentration of bilirubin-glucuronides, and hepatic and biliary glutathione concentrations. Hepatic heme oxygenase activity increased 360% 24 h after treatment but returned to control levels by 72 h. Total biliary concentrations of the mono- and diglucuronides of bilirubin (BMG and BDG) were increased 47% at 24 h and returned to control levels more slowly than did heme oxygenase. Bile flow was not significantly changed at any time. Concentrations of hepatic reduced and oxidized glutathione (GSH and GSSG) tended to increase after cobalt, but changes were not statistically significant. Biliary GSH and GSSG increased 1 h after cobalt treatment and were twice control values 3 h after treatment. These biliary glutathione concentrations declined to the control range by 6 h. These results demonstrate that increased liver heme oxygenase activity following cobalt treatment may be associated with elevated biliary excretion of bilirubin glucuronides. However, changes that occurred in biliary excretion of glutathione in response to cobalt treatment were not accompanied by parallel changes in hepatic glutathione levels.

Animals↗

PubMed1984

Treatment of mobile phase particulate matter in low-angle quasi-elastic light scattering.

The method of quasi-elastic laser light scattering (QLS), particularly at low forward scattering angles, has been complicated by the transient presence of Mie or large Rayleigh scattering particles which contaminate the scattering volume. These large contaminating particles have substantial effects on photon correlation spectroscopy because the presence of these larger scatterers tends to decrease the value of the apparent diffusion coefficient of the particle of interest. A method is presented which yields more accurate diffusion constants by autocorrelation of selected photon count periods representative of minimal Mie or large Rayleigh particle contamination. This method was applied to the determination of the apparent diffusion constant for four proteins-ovalbumin, chymotrypsinogen-A, bovine serum albumin, and ribonuclease-A.

Animals↗

PubMed1984

Correction of anomalous covariance functions in low-angle quasi-elastic light scattering.

The application of low-forward angle quasi-elastic light scattering to characterization of biological systems has been limited by maximal sensitivity of this approach to the transient presence of large Rayleigh or Mie scattering particles which contaminate the scattering volume. These particles result in anomalous autocovariance curves which translate to erroneous estimates of particle diffusion constants and Stokes radii. We have systematically considered two approaches to correct the cause of such anomalies before the autocorrelation step. This work has led to workable methods that allow low-angle quasi-elastic light scattering to provide reliable estimates of particle size. The approaches are useful in correcting errors due not only to 'dust' but also to more rapidly moving scatterers. To illustrate the method, bovine serum albumin and ovalbumin were used as example proteins.

Light↗