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Biomedical subjects

H Halpern

Publications and source records attributed to H Halpern.

At least 19 recordsLinked to original sources

Late rectal sequelae following definitive radiation therapy for carcinoma of the uterine cervix: a dosimetric analysis.

PURPOSE: This study attempted to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients treated with radiation therapy (RT) for cervical carcinoma. METHODS AND MATERIALS: A total of 183 patients with cervical carcinoma (67 Stage I, 93 Stage II, and 23 Stage III) treated with definitive RT with a minimum of 2 years follow-up were evaluated. Treatment consisted of external beam pelvic RT (EBRT) followed by intracavitary RT (ICRT) consisting of one or two insertions. Complications were scored and analyzed as a function of 25 patient and treatment factors. Conventional total rectal doses were obtained by adding together the EBRT and ICRT rectal doses. To account for differences in dose rate between the ICRT and EBRT, and variations in EBRT fractionation schemes, biologically equivalent rectal doses (BED) were calculated using a linear quadratic model. In addition, the influence of the varying proportions of EBRT and ICRT rectal doses were evaluated. RESULTS: Twenty-eight patients (15.3%) developed late rectal sequelae (13 Grade 1, 3 Grade 2, and 12 Grade 3). Diabetes (p = 0.03), Point A dose (p = 0.04), and conventional EBRT dose (p = 0.03) were the most significant factors on multivariate analysis. Logistic regression analysis demonstrated a low risk (<10%) of late rectal sequelae below conventional and biological rectal doses of 75 Gy and 135 BED, respectively. The percentage of rectal dose delivered by the EBRT significantly influenced the dose-response relationship. A defined threshold percentage above which rectal sequelae were more common was identified over the range of doses evaluated. This threshold was 87% at a total rectal dose of 60 Gy and decreased to 60% at 80 Gy. CONCLUSION: Diabetes, Point A, and EBRT doses are the most significant factors associated with the risk of late rectal sequelae in patients treated with RT for cervical carcinoma. The percentage of rectal dose delivered by the EBRT significantly affects the conventional and biological dose-response relationship. This suggests that the volume of rectum irradiated is an important and independent parameter in the development of late rectal sequelae.

Adult

Analysis of weekly complete blood counts in patients receiving standard fractionated partial body radiation therapy.

PURPOSE: Hematopoiesis is among the most sensitive systems in the body to radiation. Routine complete blood counts (CBCs) are common in clinical radiotherapy practice. Only a few studies have attempted to characterize the behavior of peripheral blood levels during partial body radiation therapy with field sizes smaller than those used in hemibody or total nodal irradiation. Such information is needed to identify which patients are at risk for cytopenia and require close monitoring. METHODS AND MATERIALS: In 1993, 412 new patients were seen at Michael Reese Hospital for radiotherapy. A total of 972 weekly CBCs were identified for 155 patients receiving a minimum of 5 weeks of treatment for breast, prostate, lung, gynecological, or head and neck malignancies. Linear regression models were fitted to the weekly CBC values for those patients who had pretreatment CBC values recorded. Factors affecting starting levels, rates of decline, and nadirs during treatment were determined for leukocytes, platelets, and hemoglobin. RESULTS: Leukocytes declined most dramatically during the first week of treatment (16% from pretreatment to Week 1 levels) and then at a rate of 3.3% per week from Week 1 to Week 7 (p < 0.001). Total mean leukocyte decrease over 7 weeks of therapy was 30%. Platelets declined 9% on average during the first week of therapy and then at a mean rate of 1.4% per week (p < 0.02). A statistically significant decrease in hemoglobin levels could not be detected. No difference in the rate of decrease could be found for different disease sites, age groups, or amount of marrow irradiated. The effects of chemotherapy were variable, depending on blood element and whether therapy was sequential or concomitant. The odds of a nadir < 2000 counts/mm3 for white blood count (WBC), < 50,000 counts/mm3 for platelets, and < 8.0 g/dl for hemoglobin were all well below 5%. A strong correlation existed between starting CBC values and nadirs; patients with lower Week 1 CBC levels were most likely to have the lowest nadirs. CONCLUSIONS: Low CBC levels during radiation therapy are likely to be the result of other medical problems that cancer patients face. Regional irradiation with small field sizes (< 40% of total body marrow) typically used in clinical radiotherapy is unlikely to be the cause of marrow depression significant enough to warrant medical intervention. Blood levels taken during the first week of treatment (Week 1) can be used to determine risks of developing critical nadirs. Localized breast and prostate cancer patients are unlikely to require routine CBCs if initial levels are normal. Routine CBC levels on all radiation oncology patients without other reasons for hematopoietic depression requires reevaluation, as millions of dollars are spent on unnecessary testing. If weekly CBC blood levels are avoided in localized breast and prostate cancer patients, this alone could potentially result in a savings of as much as $40 million a year nationally.

Adult

Results of a study to correlate serum prostate specific antigen and reproductive hormone levels in patients with localized prostate cancer.

This cross-sectional study was undertaken to determine whether serum hormones (free testosterone, androstenedione, luteinizing hormone, or prolactin) have any influence on serum prostate specific antigen (PSA) levels in patients with stage A-C prostate cancer. Blood samples were collected prior to any treatment in 36 patients; in 19 (group 1), three blood samples were collected 10 minutes apart between 9:00 AM and 9:30 AM for each patient and pooled together to avoid diurnal and episodic variation in serum testosterone values. In the remaining patients, only one sample could be collected (group 2). Free testosterone, androstenedione, luteinizing hormone, prolactin, and PSA levels were determined with appropriate radioimmunoassay techniques. Statistical analyses were performed separately for groups 1 and 2, and then with pooled data. None of the hormones in any of the analyses showed any association to serum PSA values except for prolactin for the pooled data and for group 2. This statistical significance for prolactin disappeared on multivariate analysis. There were 21 African-American men and 15 whites in the study; no racial differences in hormonal levels were found except for lower luteinizing hormone levels in African Americans in group 2 and pooled data. No differences were found between group 1 and group 2 in the mean serum prolactin and luteinizing hormone values. Serum free testosterone, androstenedione, and luteinizing hormone appeared to have no influence on serum PSA values in nonmetastatic cancer patients. Serum prolactin values were inversely associated with PSA values in univariate analysis for the pooled data; this disappeared in multivariate analysis. Unlike other studies that found higher serum testosterone levels in African-American college students than whites, no such differences were seen in this age group. Luteinizing hormone was lower in African-American men than in whites in the pooled study population. Further studies are needed to clarify our findings.

Black or African American

Patterns of failure of complete responders following high-dose chemotherapy and autologous bone marrow transplantation for metastatic breast cancer: implications for the use of adjuvant radiation therapy.

PURPOSE: To determine the pattern of failure and outcome of patients achieving a complete response following high-dose chemotherapy and autologous bone marrow transplantation for metastatic breast cancer, and to evaluate the use of involved field radiation therapy in this setting. METHODS AND MATERIALS: Thirty-one patients with metastatic breast cancer treated on three successive high-dose chemotherapy and autologous bone marrow transplantation trials between January 1987 and March 1992 who achieved a complete response were evaluated. Twenty-three patients (74.2%) had initially Stage I-II disease. Initial therapy consisted of mastectomy in 19 (74.2%), adjuvant chemotherapy in 19 (61.3%), and adjuvant radiation therapy in 11 (35.5%). All patients underwent induction chemotherapy prior to high-dose intensification. High-dose chemotherapy consisted of cytoxan, thiotepa +/- carmustine. Fourteen patients received radiation therapy prior to (7) or following the high-dose chemotherapy (7) with either the intent to palliate a symptomatic disease site (4) or to attain/maintain a complete response (10). The four palliatively treated sites received 30 Gy in 3.0 Gy fractions, the sites treated definitively received a mean dose of 43.9 Gy (range, 18-64.8 Gy) in 1.5-2.0 Gy fractions. Seventy-two disease sites were present in the 31 patients. The most common sites involved were nodal (23), bone (14), and chest wall/breast (11). Nineteen sites were bulky (> 2 cm in size). Twenty-three sites were irradiated (19 definitively, 4 palliatively). Median follow-up was 18 months (range, 2-49 months). RESULTS: Twenty (64.5%) of the 31 patients relapsed. Eleven of the 17 patients not receiving radiation failed. Seven (63.6%) failed first solely in sites of previous disease involvement and four (36.4%) failed in new sites. This failure pattern was reversed in the patients receiving radiation therapy. Nine of the 14 (64.3%) patients relapsed. Two (22.2%) failed solely in old sites and six (66.7%) solely in new sites. One patient (11.1%) failed simultaneously in both old and new sites. Patients receiving radiation therapy had a similar 2-year actuarial disease-free survival compared to those not treated with radiation (28.3% vs. 32.1%) (p = 0.14). However, patients with less than three sites of disease had a better disease-free survival at 2 years with the addition of radiation therapy (30.0% vs. 17.6%) (p = 0.03). Patients with locoregional disease only had a lower rate of local failure (one out of four vs. three out of five) and a longer mean time to any failure (4.0 months vs. 17.5 months) with the addition of radiation therapy. Of the 72 sites identified, 59 (81.9%) were amenable to radiation therapy either prior to or following the transplant. The use of radiation therapy resulted in a borderline significant improvement in 2-year actuarial control of all sites (82.4% vs. 64.3%) (p = 0.09) as well as of bulky sites (80.0% vs. 51.4%) (p = 0.08). Excluding the four sites treated with palliative intent only, the 2-year actuarial local control of the irradiated sites was 92.8%. None of the 14 treated patients experienced untoward sequelae. CONCLUSION: The predominant site of initial failure in patients with metastatic breast cancer achieving a complete response following high-dose chemotherapy and autologous bone marrow transplantation is in sites of previous disease involvement. Radiation therapy given in conjunction with the high-dose chemotherapy is capable of improving the control of these sites, the majority of which are amenable to treatment with radiation therapy. Our data suggests that patients with less than three sites of disease, bulky disease, and locoregional disease only should be considered for radiation therapy in addition to high-dose chemotherapy.

Adult

Rapid inhalation induction with halothane-nitrous oxide for myasthenic patients.

Rapid inhalation induction (RII) was successfully employed for patients without myopathy. Inhalatory agents can be used for anaesthetic induction of myasthenics, avoiding the use of neuromuscular blocking agents. We studied the use of RII in 15 myasthenics (MG) and in 15 normal subjects (nMG), measuring induction time (TI), cardiorespiratory effects, complications, and evaluated the patient's reaction to RII. The patients were submitted to elective transsternal thymectomy (MG) and gynaecological or lower abdominal surgery (nMG). No premedication was used. After preoxygenation, RII was started using a mixture of 4% halothane and O2:N2O (1:2). They performed three vital capacity breaths, followed by normal spontaneous ventilation. The TI was assessed by timing the loss of verbal command (TLVC) and loss of eyelid reflex (TLER). Systolic and diastolic pressure, pulse oximetry, capnometry, respiratory rate (RR) and heart rate (HR) were measured during induction at each minute, for four minutes. After a postanaesthetic questionnaire only two normal subjects did not like the RII technique. Mean values for TLVC and TLER were 67 and 73 sec for MG and 64 and 69 sec for nMG, respectively. There was no change in HR for MG or blood pressure. The RR increased in both groups, but no change in PetCO2 was observed; SaO2 was > 97%. In conclusion, RII can be performed rapidly and safely in myasthenic patients and is a technique that should be considered for the induction of anaesthesia in myasthenic patients.

Adult

Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: preliminary results of a randomized, open-labeled, phase II trial.

PURPOSE: To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy. METHODS AND MATERIALS: This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy +/- chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the "treatment arm" receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale. RESULTS: Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1-6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl. CONCLUSION: (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.

Adenocarcinoma

Acute toxicity during external-beam radiotherapy for localized prostate cancer: comparison of different techniques.

PURPOSE: The chronic and acute toxicities associated with conventional radiotherapy of localized prostate cancer are well documented. However, the degree and incidence of toxicities with conformal techniques are not known. Studying side effects associated with modern radiotherapeutic techniques is more important now since there has been a general trend to use computerized tomography-based techniques in recent years; beam's eye view-based conformal techniques are also becoming more commonplace. It is possible that the local disease control can be improved with the delivery of higher doses than currently used. Conformation of the treatment volume to the target volume may facilitate such dose-escalation. However, prior to such dose-escalation, it is important to know the toxicities associated with such techniques with conventional doses. METHODS AND MATERIALS: We have compared week-by-week acute toxicities associated with conventional (Group A, 16 patients), computerized tomography-based, manual (Group B, 57 patients) and beam's eye view-based (Group C, 43 patients) techniques during 7 weeks of radiotherapy. Group B and C patients were treated contemporaneously (1988-1990). RESULTS: Acute side effects gradually increased from week 1 through weeks 4-5 and generally declined or plateaued after that. The incidence of acute toxicities was significantly less with the beam's eye view/based technique than with the other two methods. For instance, the percentages of Grade 2 acute genitourinary toxicities for Groups A, B, and C were as follows: Week 1-0, 0, 0; Week 2-6, 0, 0; Week 3-6, 9, 2; Week 4-12, 14, 9; Week 5-35, 14, 9; Week 6-31, 16, 7; Week 7-33, 8, 8, respectively. The p values associated with differences in acute genitourinary toxicities for Weeks 1-7 using chi-square test were 0.072, 0.627, 0.389, 0.538, 0.123, 0.06, and 0.012; the p values for acute gastrointestinal toxicities were 0.512, 0.09, 0.031, 0.031, 0.003, < 0.0001, and 0.004, respectively. Pairwise comparison (Wilcoxon rank-sum test) showed statistically significant lower acute toxicity in Group C than Group B (e.g., p values, Weeks 1-7 for gastrointestinal toxicity: 0.633, 0.056, 0.010, 0.014, < 0.0001, < 0.0001, and < 0.0001, respectively) in the latter part of the treatment course. No correlation was found between the extent of toxicity and the patient age or the overall treatment time. Also, no correlation was found between the degree of toxicity and the radiation dose and fraction size, within the narrow ranges used (65-70 Gy and 180-200 cGy, respectively). A trend suggesting increased severity of toxicity with increase in the volume of treatment was seen. CONCLUSION: The findings in this retrospective study need to be confirmed by other prospective studies.

Acute Disease

Word-finding abilities of three types of aphasic subjects.

Word-finding difficulties are often observed among different types of aphasic patients. This investigation analyzed the word-finding abilities of 30 aphasic subjects (10 Broca's, 10 Wernicke's, and 10 anomic). Forty nouns counterbalanced according to word length and frequency of occurrence in English language usage were used as stimuli and presented through four modalities (oral expression, writing, auditory comprehension, and reading comprehension). It was expected that patterns of word finding abilities would help in the classification of the different types of aphasia. In addition, long words and less frequently occurring words in English language usage should prove more difficult in word-finding ability, regardless of modality. The results of this study found long words and less frequent words were more difficult for aphasic subjects. Among the modalities, long words were significantly harder than short words for the writing modality only. It was also found that semantic errors were the most common errors for all types of aphasic subjects. Broca's subjects produced significantly more no response errors in oral expression; Wernicke's subjects produced significantly more semantic and phonemic errors in reading comprehension; and, Wernicke's subjects produced significantly more unrelated errors in both oral expression and reading comprehension. Clinical implications were also discussed.

Aged

The use of beam's eye view volumetrics in the selection of non-coplanar radiation portals.

In 3-dimensional treatment planning, beam's eye view (BEV) is used as an interactive tool to define portal entry angles that exclude critical structures while fully encompassing the target volume. With beam's eye view volumetrics (BEV volumetrics), the volume of intersected normal tissues is also calculated and is used as a quantitative tool to choose portal orientations that minimize normal tissue volumes irradiated. The axial beam entry angle and a polar angle (relative to the patient longitudinal axis) are specified to define the central axis orientation. Using BEV volumetrics, we have studied the quantities of normal tissues irradiated when treating tumors in the abdomen, thorax, and pelvis. The reduction of normal tissue irradiated is a strong function of site and patient-specific tumor size and location. Volumetrics combined with BEV is found to be useful in treatment planning because it (a) provides quantitative information needed in rationally choosing portal entry angles, (b) provides a near interactive speed approach to understanding the relative merits of different multiple field plans, and (c) compliments the information provided by the more time-consuming generation of dose volume histograms.

Humans

Beams eye view-based photon radiotherapy I.

Geographic miss, dosimetric miss (underdosing), and proximity of the tumor to sensitive normal tissues are some of the causes of inadequate radiation dose delivery; this is one of many causes of failure after radiotherapy. In the past decade, computerized tomography (CT)-based treatment planning has helped to overcome some of these problems. Beam's eye view (BEV)-based radiotherapy planning is an improvement over CT-based treatment planning that may further increase the therapeutic ratio. Since January 1988, we have treated 198 patients with BEV-based photon radiotherapy. About 40% of our patients treated with radical radiotherapy undergo BEV-based treatment, and about 70% of patients who undergo planning CT in the treatment position receive BEV-based radiotherapy. Our findings are as follows: (a) routine use of BEV-based RT (BEVRT) is possible in a busy radiation oncology department; (b) BEVRT improves geometric coverage of tumors; (c) BEVRT is extremely useful in the design of oblique portals; (d) time commitments for various members of the RT treatment-planning team are reasonable; (e) BEVRT helps individualize RT technique; (f) preliminary data suggest decreased acute toxicity with the use of BEVRT for prostate cancer patients. Whether these advantages will help to improve the outcome (i.e., improve local control and survival) and/or decrease the long-term toxicity is not yet known.

Breast Neoplasms

The nonfluencies of eight psychiatric adults.

Nonfluencies of eight psychiatric adults were evaluated through seven tasks: verbal formulation; conversational spontaneous speech; picture description; sentence reading; paragraph reading; automatic speech; and repetition of phrases and sentences. Results indicated that 12% of total subject output were nonfluences. Most nonfluencies occurred on tasks involving verbal formulation, picture description, spontaneous speech, and reading aloud of sentences and paragraphs, and least in automatic speech, and repetition of phrases and sentences. The nonfluencies were mostly repetitions, followed by hesitations and then prolongations. The nonfluencies appeared mostly on sounds, with words and phrases the next frequent, and sentences and syllables the least frequent. Finally the most nonfluencies occurred on words in the middle or beginning of sentences, with the least occurring on words at the end of sentences.

Adult

Word-association responses to time-altered stimuli by schizophrenic adults.

This research addressed the relationship between the speed of presentation of stimuli through the auditory and visual modalities and the number of syntagmatic and paradigmatic word-association responses of 49 chronic undifferentiated schizophrenic adults. In word-association tests administered to subjects stimuli were balanced for frequency of occurrence in written English language (frequent, infrequent), word length (long, short), abstraction level (low, medium, high), and part of speech (noun, verb, adjective). The words were presented auditorily at normal speed (equivalent to 10 phonemes per second) and at half speed (equivalent to 5 phonemes per second) speech. Words were also presented visually, using a tachistoscope, at extended fixation speed (equivalent to 1,000 msec.) and at sweep speed (equivalent to 10 msec.). More paradigmatic responses occurred on word stimuli if nouns, long, and frequently occurring presented auditorily; and if concrete, nouns, and presented slowly and visually. Results were compared to previously reported data for aphasic and normal adults, and differentiating features and clinical implications were discussed.

Adult

Mixed olfactory neuroblastoma and carcinoma. A report of two cases.

Two cases of olfactory neuroblastoma mixed with other neoplastic elements are reported. One tumor contained foci of adenocarcinoma and of ganglioneuroblastoma in addition to an undifferentiated small cell component consistent with neuroblastoma; the other tumor histologically resembled small cell undifferentiated carcinoma with foci of squamous differentiation, but was shown by electron microscopy to be neuroblastoma. The histogenesis and treatment of mixed tumors of this type are discussed.

Adenocarcinoma

Differential language characteristics in adult aphasic and schizophrenic subjects.

Sixty-one adult aphasic and 61 noncerebrally involved chronic undifferentiated schizophrenic subjects were tested for impairment in 10 language categories. Results indicated that the language categories of strongest differentiating value were writing of words to dictation, naming, syntax, where aphasic subjects were more impaired in all three, and relevance, where schizophrenic subjects were more impaired. To a lesser extent, other differentiating language features were auditory retention span, and overall language ability, where aphasic subjects were more impaired in both, and fluency, where aphasic subjects were less fluent. Both groups also were tested for apraxia of speech, oral apraxia, limb apraxia, time and place orientation, and ability to respond to questions containing general information.

Adult

Work association of time-altered auditory and visual stimuli in aphasia.

A word association test was administered to a group of 32 aphasic adults and to a control group of 32 normal adults similar in age, sex, and education. Word stimuli were balanced according to frequency of occurrence in written English language usage (frequent, infrequent), word length (short, long), abstraction level (low, medium, high), and grammatical class (noun, verb, adjective). Stimuli were presented auditorily at normal speed (equivalent to 10 phonemes per sec) and at half speed (equivalent to 5 phonemes per sec) speech. When word stimuli were presented at half speed (slower), the aphasic adults but not the controls produced significantly more paradigmatic (same grammatical class) responses. Twenty aphasic subjects and twenty controls supplied association responses to words presented tachistoscopically at fixation speed (equivalent to 250 msec) and at sweep speed (equivalent to 10 msec). When word stimuli were shown for a longer time, the aphasic adults but not the controls produced significantly more paradigmatic responses. Also analyzed were paradigmatic responses to the word association test produced in relation to frequency of occurrence, word length, levels of word abstraction, and grammatical class.

Adult

Phonemic behavior of aphasic subjects without dysarthria or apraxia of speech.

Thirty adult aphasic subjects without apraxia of speech or dysarthria were tested for their ability to produce phonemes in single test words and in spontaneous contextual speech. Results indicated that 75% of the total phonemic errors were due to a whole-word phenomenon apparently associated with faulty processing of the word rather than faulty production of the phoneme. True phonemic errors comprised 25% of the total errors or about 2% of all responses. Phoneme substitutions were by far the most frequent error (61%). Of the 30 subjects, 28 made no phonemic errors in spontaneous contextual speech. Aphasic behavior is not characterized by significant breakdown of articulatory performance. Observed patterns of error do not clearly support a phonemic regression hypothesis.

Adolescent