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Biomedical subjects

D S Shimm

Publications and source records attributed to D S Shimm.

At least 37 records · Page 2Linked to original sources
PubMed1991

Light chain composition of serum granulocyte binding immunoglobulins.

Serum granulocyte binding IgG, IgM, and the light chain composition of granulocyte binding immunoglobulins were measured in 58 adult subjects, including 8 normal individuals, 6 with Felty syndrome, 6 with chronic idiopathic neutropenia, 32 with B-cell chronic lymphocytic leukemia (CLL), and 6 with multiple myeloma. An abnormal kappa/lambda ratio of granulocyte binding immunoglobulins was detected in 12 of 32 patients with CLL. Neutropenia in patients with CLL did not correlate with an abnormal kappa/lambda ratio or excess granulocyte binding IgG, but did correlate with granulocyte binding IgM (P less than 0.02). Eight of the 12 patients (5 with chronic idiopathic neutropenia and 3 with Felty syndrome) with an immune neutropenia without underlying neoplastic disorder had light chain restricted granulocyte binding immunoglobulins. Of all patients' sera with light chain restriction, 76% were of lambda light chain isotype. Thus, the frequent detection of light chain restriction of granulocyte binding immunoglobulins is not a reflection of malignancy but is suggestive of the somatic mutation of immunoglobulin light chain genes.

Felty Syndrome↗
PubMed1991

Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial.

Hyperthermia delivered by scanned focused ultrasound was combined with external beam radiation to treat 15 patients with primary malignant tumors of the brain. A preliminary craniectomy was performed to avoid attenuation of the ultrasound beam by the skull, and multiple thermal sensors were employed to ascertain intratumoral temperatures. The target temperature was 42.5 degrees C at the tumor boundary. This was attained at more than one point during every complete treatment, while a mean temperature in excess of 42 degrees C was achieved within the scanned tumor volume during at least 1 treatment in 11 patients. Technical problems and toxicities are described.

Adolescent↗
PubMed1991

Development of scanned focussed ultrasound hyperthermia: clinical response evaluation.

Selective heating of irregularly shaped tumors at depth can now be accomplished through focussing and controlled scanning of energy deposition patterns by ultrasound. A scanned focussed ultrasound (SFUS) hyperthermia system developed at the University of Arizona has been used to deliver 220 treatments to 87 tumors in 71 patients with extracranial malignancies between October 1986 and May 1990. Patients received an average of three SFUS hyperthermia treatments, spaced weekly, during ongoing fractionated radiotherapy. The most common anatomic sites treated were the pelvis (22 patients), chest wall or breast (14), neck (8), and axilla (7), while the most common histologies were adenocarcinoma (36), squamous cell carcinoma (11), and melanoma (10). Concurrent radiotherapy was delivered (range 1000-7640 cGy, mean 4320 cGy) to 67 SFUS hyperthermia patients; 4 received concomitant chemotherapy. Tumor volumes ranged from 1-2100 cubic centimeters (mean 325 cc), and 75% were located at depths greater than 3 cm from skin. A 62% overall response rate was observed, with 22% of treated tumors demonstrating a complete response (defined as complete disappearance of treated tumor), and 40% exhibiting a partial response (defined as greater than or equal to 50% reduction in tumor volume). Dramatic local pain reduction was achieved in 42% of the tumors treated. The acute tolerance of SFUS hyperthermia was quite good, and chronic toxicities (persistent skin blisters/burns) were identified in two patients. The versatility of the SFUS system is discussed, as well as its future potential for improving control of advanced loco-regional malignancies treated with curative intent.

Combined Modality Therapy↗
PubMed1991

Radiation therapy for squamous cell carcinoma of the skin.

Eighty-five squamous cell skin cancers treated with radiation therapy were reviewed, including 23 untreated primary tumors, 6 recurrent tumors, 16 synchronous or metachronous nodal metastases including 3 patients from the previous two groups, and 38 sites irradiated for microscopic residual cancer after surgery. The 5-year actuarial local controls were 0.54, 0.0, 0.42, and 0.79, respectively. No relationship between local control and either tumor size or radiation dose could be shown. Salvage treatment was attempted in 7 of 32 local failures, and has been successful in 4. Cancers arising in the settings of prior irradiation, renal transplant, hematopoietic malignancies, or chronic inflammation did not fare worse, and patients with parotid node metastases generally fared better with combined irradiation and surgery. Surgery followed by adjuvant irradiation confers a 5-year disease control probability of 0.79. Irradiation alone for untreated primary lesions, for recurrent primary lesions, or for untreated nodal metastases confers a disease control probability of approximately 0.50. Local or systemic predisposing factors do not confer an appreciably different prognosis. Parotid lymph node metastases are best served by combined modality treatment.

Carcinoma, Squamous Cell↗
PubMed1991

Recurrent basal cell carcinoma treated with radiation therapy.

A retrospective study was performed of 61 recurrent basal cell carcinomas treated with radiation therapy between 1974 and 1990 at the University of Arizona College of Medicine or at Southwestern Radiation Oncology, Tucson, Arizona. The median length of follow-up was 57 months. Applying the American Joint Committee on Cancer staging system to these recurrent tumors, 36 were stage I, 19 were stage II, five were stage III, and one was stage IV. Kaplan-Meier methods were used to estimate the 5-year complete remission rates. The Mantel-Haenszel Test and the Cox Proportional Hazards Model were used to determine if tumor size, stage, histologic subtype, anatomic site, age, sex, dose, number of radiation therapy treatments, length of time over which the radiation therapy was administered, or type of radiation beam used (orthovoltage x-rays vs megavoltage electrons) affected the 5-year complete remission rates. Only tumor size and stage had a statistically significant effect on the complete remission rates. The Kaplan-Meier estimates of the 5-year complete remission rates for 0.5- to 1.0-cm tumors vs tumors larger than 1.0 cm were 96% (95% confidence interval, 88% to 100%) and 81% (95% confidence interval, 64% to 99%), respectively. The Kaplan-Meier estimates of the 5-year complete remission rates for stage I/II tumors vs stage III/IV tumors were 93% (95% confidence interval, 85% to 100%) and 42% (95% confidence interval, 8% to 84%), respectively. Functional and cosmetic results were frequently good to excellent at 5 years. Soft-tissue necrosis developed in two of 61 cases, and was successfully managed in both. This article, combined with a review of the literature, suggests that radiation therapy is an effective method of treating recurrent basal cell carcinomas.

Adult↗
PubMed1991

Idiopathic neutropenia: antineutrophil antibodies and clinical correlations.

PURPOSE: The present study was done to evaluate the clinical characteristics of a large series of adult patients with chronic idiopathic neutropenia, and correlate the presence of antineutrophil antibodies, their class (IgG or IgM), and their ability to fix complement with clinical parameters, including other hemocytopenias, splenomegaly, and infections. PATIENTS AND METHODS: One hundred twenty-one adult patients with chronic idiopathic neutropenia were studied. Serum neutrophil-binding antibodies were measured using paraformaldehyde-fixed granulocytes (PFGs) from normal volunteers as target cells. 125I-labeled staphylococcal protein A was used to detect IgG antibodies while IgM antibodies were detected by using 125I-labeled mouse monoclonal anti-IgM antibody. Sera containing antineutrophil antibodies were tested for their ability to fix complement on donor PFGs by using 125I-labeled monoclonal antibody to the third component of complement. RESULTS: Of the 121 patients with chronic idiopathic neutropenia, 71 patients had isolated neutropenia, while 50 had neutropenia combined with either anemia and/or thrombocytopenia. Among the 71 patients with isolated neutropenia, there were 51 females (72%), compared with 28 females (56%) among the 50 patients with combined hemocytopenias (p = 0.083). Patients with multiple hemocytopenias were significantly older (p less than 0.01), were more likely to demonstrate splenomegaly (p = 0.001), and may have had more infectious complications. From all the patients, 36% of sera were shown to have antineutrophil antibodies, with a non-significant trend for these to be found more frequently in patients with multiple hemocytopenias. Sera with mixed IgG-IgM antineutrophil antibodies were significantly more likely to fix complement than those with isolated IgG or IgM antibodies, and among the patients with antineutrophil antibodies, complement-fixing antibodies were significantly associated with multiple hemocytopenias. Splenomegaly was significantly associated both with antineutrophil antibodies (p = 0.008) and with infections (p = 0.007). Antineutrophil antibodies were not associated with infections. CONCLUSIONS: Approximately one third of adult patients with idiopathic neutropenia have IgG and/or IgM antineutrophil antibodies demonstrable in their serum. There is a subset of patients with idiopathic neutropenia with multiple hemocytopenias who tend to be older, less likely to show female predominance, more likely to have splenomegaly and infections, and more likely to have antineutrophil antibodies, especially mixed IgG-IgM and complement-fixing antibodies.

Adult↗
PubMed1990

The role of radiotherapy in the treatment of malignant sweat gland neoplasms.

Malignant sweat gland neoplasms are rare tumors. Historically, the principal mode of treatment has been local surgical excision. Eight published studies show that greater than 50% of patients develop either local tumor recurrence after surgery or regional lymph node metastases. Most patients have evidence of locoregional failure before distant metastases are detected. Three patients were recently referred to the University of Arizona Cancer Center for consideration of irradiation after resection of such tumors. In two patients, the tumor was located on the scalp and, in one patient, on the alar surface of the nose. Their ages ranged from 19 to 60 years. All underwent surgical resection followed by high-dose irradiation of the surgical bed (approximately 70 Gy) and regional lymphatic chains (approximately 50 Gy). Two patients remain disease-free at 27 and 35 months, respectively, after completion of treatment; the third died of rapidly progressive systemic metastases. A review of the literature is provided focusing on treatment success and predominant patterns of recurrence. Finally, a rational approach for evaluation of patients that might benefit from local irradiation is presented.

Adenoma, Sweat Gland↗
PubMed1990

Interstitial thermoradiotherapy: thermal dosimetry and clinical results.

From August 1977 to August 1986, 72 patients with advanced primary or recurrent cancers were treated using interstitial thermoradiotherapy. Sites treated included the pelvis in 49 patients, the head and neck in 15, and other sites in six. Median tumor volume was 52 cm3, and all but nine patients had received prior irradiation. In 69 patients, hollow stainless steel catheters were implanted and used as electrodes with a 0.5 MHz radiofrequency (RF) generator, whereas in three patients, standard plastic Henschke tubes were used with a commercially available interstitial microwave (MW) system operating at 915 MHz. Most patients were heated intraoperatively for 30 minutes, aiming for a minimum measured intratumoral temperature (Tmin) of 42 degrees C. The implant was occasionally preceded by external irradiation, and after hyperthermia, the catheters were afterloaded with 192Ir for brachytherapy. Tmin exceeded 42 degrees, 42.5 degrees, 43 degrees, and 44 degrees in 25, 16, 12, and 3, respectively, of 70 patients with temperature data available, and the probability of successful heating was independent of tumor volume or site. Twenty-five of 69 (36%) evaluable patients achieved a complete response (CR). Probability of CR demonstrated a significant univariate dependence upon Tmin, radiation dose, site treated, and tumor volume, but multivariate analysis showed only three significant predictor variables: tumor volume, radiation dose, and Tmin. The probability of a CR ranged from 95% for patients with small tumors receiving high doses of radiation and adequate heat, to 5% for patients with large tumors receiving low radiation doses and less than adequate heat. Of 25 patients with CR, 10 relapsed; median response duration was less than 18 months, depended marginally upon disease site, and was independent of Tmin, radiation dose, and tumor volume. Seventeen patients sustained a complication, of which nine were severe enough to require hospitalization or surgery. All severe complications occurred in patients with pelvic tumors. The probability of a complication of any severity had a significant univariate association with maximum intratumoral temperature (Tmax) and tumor size. We conclude that interstitial thermoradiotherapy offers the promise of heating large tumors in locations where externally applied hyperthermia has not been successful.

Brachytherapy↗
PubMed1990

Polyamine biosynthesis inhibitors combined with systemic hyperthermia in cancer therapy.

A Phase I clinical trial has been initiated at the University of Arizona Cancer Center which combines escalating oral doses of the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO), with systemic hyperthermia (approximately 41.5 degrees C) in the treatment of metastatic melanoma. The rationale for the combination of hyperthermia and polyamine biosynthesis inhibitors in the treatment of human cancers includes studies which show that depletion of endogenous polyamines, as a result of treatment with DFMO, sensitizes both rodent and human tumor cells to the cytotoxic effects of hyperthermia. Heat shock induces the first enzyme in polyamine catabolism, spermidine/spermine N1-acetyltransferase (N1-SAT). The consequently acetylated forms of spermidine and spermine are then constitutively oxidized by the enzyme polyamine oxidase (PAO). Both CHO and human A549 lung cancer cells exhibit heat-inducible polyamine acetylation, display potent heat sensitization after polyamine depletion, and ultimately reveal prolonged expression of thermotolerance. Conversely, HeLa cells do not demonstrate heat-inducible polyamine catabolism, are not sensitized to heat with DFMO, and display more rapid kinetics of thermotolerance decay. These laboratory studies suggest that enhancement of the cytotoxic action of hyperthermia by DFMO occurs as a consequence of the inhibition of polyamine catabolism, a heat-inducible process that affords some form of protection to cells undergoing heat stress. Human melanoma cultures demonstrate heat-inducible polyamine catabolism and are sensitized to hyperthermic cytotoxicity by DFMO. To date, 24 systemic hyperthermia treatments have been delivered to nine patients with metastatic melanoma in conjunction with oral DFMO under this Phase I clinical trial.

Acetylation↗
PubMed1990

Radiation therapy for paragangliomas of the temporal bone.

Treatment of paragangliomas of the temporal bone (glomus jugulare and glomus tympanicum tumors) is controversial, with both surgery and radiation therapy having their advocates. This paper discusses the experience at the University of Arizona Health Sciences Center in treating 10 cases of this uncommon tumor between 1971 and 1988. Seven of 10 cases were initially treated using irradiation and achieved complete tumor control for a mean of 67 months (range = 23-107 months). Two patients, one treated surgically and the other by embolization, had recurrences and were salvaged by radiation, and neither has recurred. The final patient is disease-free 9 months after embolization and surgery. There have been no serious sequelae of treatment. We conclude that moderate-dose irradiation can safely control most temporal bone paragangliomas.

Female↗
PubMed1989

Radiation therapy for squamous cell carcinoma of the supraglottic larynx.

Sixty-five patients with invasive squamous cell carcinoma of the supraglottic larynx received irradiation with curative intent between 1975 and 1984, with a 5-year actuarial survival of 48% and a local control rate of 70%. Five-year survivals for clinical Stages I, II, and III + IV were 60, 53, and 52%, respectively; local control rates were 88, 76, and 63%, respectively. These patients included one treated with preoperative irradiation, 35 treated with surgery followed by postoperative irradiation, and 29 treated with radiation therapy alone. In the surgery plus irradiation group, 5-year local control was 93% for clinical Stages I + II (14 patients), and 61% for clinical Stages III + IV (21 patients). Three patients had pathologic Stage II disease, with the remainder demonstrating a higher pathologic than clinical stage. Multiple positive nodes predisposed to local/regional recurrence, while no relationship could be established between recurrence and extracapsular nodal spread, positive margins, emergency tracheostomy, total versus less-than-total laryngectomy, radiation field size, radiation dose, or delay until radiation therapy, probably because of patient numbers. Six patients, five with positive nodes, developed distant metastases, and three developed second primary tumors outside the head and neck region. In the radiation therapy alone group, 5-year local control rates were 86, 59, and 53% for clinical Stages I (7 patients), II (11 patients), and III + IV (11 patients), respectively. However, three of four Stage II local/regional failures were surgically salvaged for periods greater than 30 months, for an ultimate Stage II local control of 89%. No relationship could be established between local control and radiation dose or field size, again probably because of small patient numbers. Three patients developed distant metastases, and eight developed second malignancies, one within the irradiated volume. Fifteen patients developed acute toxicity during irradiation, and there were eight chronic complications, five requiring surgery; toxicity was more common in the group treated with radiation alone. Radiation therapy alone with surgical salvage is an effective, function-preserving treatment for clinical Stages I and II carcinoma of the supraglottic larynx, and appears to yield local control and survival comparable with that of combined irradiation and surgery in more advanced disease.

Actuarial Analysis↗
PubMed1989

The CDRH helix. A phase I clinical trial.

Seventeen patients have been given regional hyperthermia treatments using the Center for Devices and Radiologic Health (CDRH) Helix, a resonant helical coil unit. Most of these patients had large, clinically advanced tumors, whose mean volume exceeded 1000 cc. Mean maximum, minimum, and average temperatures were 40.6, 38.6, and 39.6 degrees C, respectively, for all sites combined. The pelvic heating capabilities of the CDRH Helix and the BSD-1000 annular phased array were compared, and generally were equivalent. Although the Helix could be used in a wider variety of locations, and was more comfortable and easier to use than the BSD-1000 annular phased array, neither device was particularly effective in generating clinically useful temperatures; the Helix is currently under investigation for use in regional-systemic hyperthermia in combination with antineoplastic drugs and biologic response modifiers.

Clinical Protocols↗
PubMed1988

Parotid lymph node metastases from squamous cell carcinoma of the skin.

Nineteen parotid lymph node metastases from squamous cell carcinoma of the skin were treated, seven with irradiation and 12 with surgery and postoperative irradiation. In the group treated with combined therapy, size of nodal metastasis and extent were strong predictors of relapse. Further postoperative irradiation with 60 Gy is not adequate to control extensive parotid nodal disease. Finally, elective treatment of clinically negative parotid nodes is not necessary in patients who can be closely followed, since early nodal disease can be controlled readily.

Carcinoma, Squamous Cell↗
PubMed1988

Radiation resistance in a multidrug resistant human T-cell leukemia line.

In clinical practice, cancers refractory to chemotherapy commonly appear to be comparatively radioresistant. One mechanism by which cancer cells become resistant to chemotherapy is pleiotropic multidrug resistance, characterized by cross resistance to a number of otherwise unrelated heterocyclic antineoplastic agents, including vinca alkaloids, anthracyclines, dactinomycin, and others. We have studied a drug sensitive human leukemia cell line, CEM; a pleiotropic multidrug resistant subline of CEM, CEM/VLB100; VLB-1, a drug sensitive revertant subline arising during in vivo passage of CEM/VLB100; and a methotrexate resistant subline of CEM, CEM-MTX. Using soft-agar colony formation after graded doses of X rays as an endpoint, we found that CEM, CEM-MTX, and CEM/VLB100 had similar terminal slopes (D0 = 0.66 Gy). However, the CEM/VLB100 survival curve had a broader initial shoulder (n = 3.0, Dq = 0.75 Gy) than did CEM (n = 1.6, Dq = 0.25 Gy) or CEM/MTX (n = 1.0, Dq = 0 Gy), suggesting that CEM/VLB100 has an increased capacity to repair radiation-induced DNA damage. This was tested by comparing the cell lines' abilities to accumulate sublethal damage. In split dose recovery experiments, CEM/VLB100 demonstrated increased ability to repair sublethal radiation damage following fractionated irradiation compared with the CEM parental line. Although it no longer demonstrated multidrug resistance, VLB-1 still displayed diminished radiation sensitivity. On the basis of these and other investigators' results, we suggest that diminished radiation sensitivity is separate from, but can be closely associated with, the multidrug-resistant phenotype.

Antineoplastic Agents↗
PubMed1988

Scanned focussed ultrasound hyperthermia: initial clinical results.

Between November 1986 and July, 1987, a preliminary study to determine the feasibility of scanned focussed ultrasound for clinical hyperthermia at various sites was conducted. Fourteen patient (17 tumors) have been treated using a microprocessor-controlled apparatus developed at the University of Arizona by modifying a commercially available diagnostic ultrasound unit. We have treated nine pelvic tumors, four extremity tumors, two brain tumors, and two extracranial head and neck tumors for a total of 42 treatments. Multipoint thermometry was achieved for all patients, with 2-25 (mean = 10) points monitored during each treatments within the scanned tumor volume. Average maximum temperature within the scanned tumor volume was 44.2, 44.7, 44.8, and 42.0 degrees C for pelvic, extremity brain, and extracranial head and neck tumors, respectively; similarly, 55%, 45%, 71%, and 0 of monitored points exceeded 42.5 degrees C. Pain limited applied power in 15 of 42 treatments, and bone pain with a periodicity similar to the scanning periodicity was seen in 11 treatments. A non-randomized comparison of temperatures achieved using scanned focussed ultrasound to those achieved using the microwave annular array and the CDRH Helix suggests that scanned focussed ultrasound may have promise and potential advantages in heating selected pelvic tumors.

Brain Neoplasms↗
PubMed1988

Nonsurgical treatments for skin cancer: retinoids and alpha-interferon.

Retinoids, the natural and synthetic analogs of vitamin A, and alpha-interferon have been used effectively in the treatment of certain cutaneous premalignancies and malignancies. Retinoids have shown impressive activity against premalignant disorders of the skin (actinic keratoses, keratoacanthoma, epidermodysplasia verruciformis) and of other epithelial sites (oral leukoplakia, cervical dysplasia). In established basal cell skin cancers, topical retinoid treatment has produced a complete response rate of 33%, and systemic retinoids have produced an objective response rate of 51%. In advanced squamous cell skin cancers, systemic retinoids have produced a response rate of over 70%. Intralesional alpha-interferon has produced impressive responses and systemic alpha-interferon has produced a 50% objective response rate in basal and squamous cell carcinoma. Retinoid therapy and alpha-interferon have produced modest overall results in melanoma, although striking individual responses have been reported. In cutaneous T-cell lymphoma, which is notably refractory to chemotherapy, retinoids and alpha-interferon have produced responses in 60%+ and 70%+ of cases, respectively. Retinoids and alpha-interferon, either alone or in combination, offer exciting prospects for primary and neoadjuvant therapy for advanced malignancy. Retinoids also show promise as relatively nontoxic preventive and adjuvant therapy. Researchers should focus on integrating these drugs with other biological response modifiers, differentiation agents, and cytotoxic drugs for treating advanced malignancy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Lethal midline granuloma with a novel T-cell phenotype as found in peripheral T-cell lymphoma.

Lethal midline granuloma (LMG), initially a clinical description, includes an uncommon group of disorders characterized by a relentless, destructive process involving the upper respiratory structures. Its etiology and pathogenesis are uncertain, probably varied, and the distinction between inflammatory and malignant processes is difficult despite extensive clinical and histopathologic evaluation. The need for new techniques for rapid diagnosis has important therapeutic implications. Using an extensive panel of T- and B-cell monoclonal antibodies the authors describe a patient with clinically and pathologically typical LMG demonstrating an "activated" T-cell phenotype with a "novel" pattern characteristic of peripheral T-cell lymphoma, strongly implying that some cases of LMG are more closely related to neoplastic T-cell lymphoproliferative disorders than to inflammatory conditions. Further studies using these immunotyping techniques may help clarify the pathogenesis of LMG, and may uncover specific diagnostic and prognostic phenotypic patterns.

Adult↗