bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous Bilateral Necrotizing Fasciitis of the Forearm: A Case Report
Authors: Kiriakopolous Elaine , Brown Mitchell H , Starr Joseph A , Choptiany Philip J , Mederski Barbara
Published: February 2017

Necrotizing soft tissue infections are seen with relative frequency. A case of spontaneous, bilateral necrotizing fasciitis of the forearms in an otherwise healthy 17-year-old male is reported. It is thought to be the only reported case of spontaneous bilateral necrotizing fasciitis.
Computed Tomography Artefacts: An Experimental Investigation of Causative Factors
Authors: Strumas N , Antonyshyn O , Yaffe MJ , Mawdsley G , Cooper P
Published: February 2017

N Strumas, O Antonyshyn, MJ Yaffe, G Mawdsley, P Cooper. Computed tomography artefacts: An experimental investigation of causative factors. Can J Plast Surg 1998;6(1):23-29.

The factors that produce computed tomography (CT) artefacts associated with craniofacial fixation devices were analyzed. The effects of attenuation, motion, partial volume and implant shape were evaluated. By using a CT phantom model with an engine to produce reproducible motion, a vitallium rod, fixation plate and blank were scanned sequentially. for each experimental condition, the degree of artefact produced was quantified by measuring the standard deviation of the CT number at standardized regions of interest, and a comparative analysis was performed. Motion produced the greatest degree of artefact. Both the frequency and direction of motion were important, with high frequency motion in the plane of the CT slice producing the greatest degree of CT artefact. Partial volume artefacts increased as the volume of material in the plane of section increased. The amount of artefact produced was dependent on the volume of material x-rays passed through the object rather than on the geometric configuration. Attenuation effects were evaluated. Results revealed that the amount of artefact was greatest between highly attenuating objects.
Carpal Tunnel Syndrome: A New Objective Evaluation Technique
Authors: Bigelow Eric , Bell Michael
Published: February 2017

E Bigelow, M Bell. Carpal tunnel syndrome: A new objective evaluation technique. Can J Plast Surg 1998;6(2):99-103.

Thumb abduction strength is impaired progressively in patients with carpal tunnel syndrome (CTS). In advanced cases abductor pollicis brevis (APB) weakness and wasting are evident. The APB muscle recovers power significantly after carpal tunnel release. A technique that objectively measures this function is described. The results of a study comparing 175 patients suffering from CTS with 132 controls are presented. No previous study has looked exclusively at the APB motor deficit preoperatively and at the postoperative recovery in CTS patients. Preoperatively, bilateral thumb abduction power was measured in patients with CTS by using a micrometer spring scale. The results were compared with those from a control group. A significant APB strength deficit was present in all CTS patients (P=0.001). A standard carpal tunnel release was performed by the same surgeon in all cases. The transverse carpal ligament was incised under direct vision with the use of an open technique. Thumb abduction strength was measured again four weeks postoperatively; significant recovery was observed in strength compared with the preoperative value (P=0.001). Thumb abduction power was, however, still lower than that of the control group (P=0.001). This test is a simple, inexpensive and reproducible way to evaluate the severity of CTS and to help diagnose patients with CTS objectively. It is a useful adjunct to monitor and follow CTS patients postoperatively.
Coronal Fractures of the Body of the Hamate: Two Case Reports
Authors: Binhammer Paul A , Rao Jaggi
Published: February 2017

PA Binhammer, J Rao. Coronal fractures of the body of the hamate: Two case reports. Can J Plast Surg 1998;6(2):81-84.

Coronal fracture of the body of the hamate with associated dorsal dislocation at the bases of the fourth and fifth metacarpals is rare. Two cases of this injury, treated with open reduction and internal fixation, are reported. As well, other reports of coronal hamate fractures are reviewed.
Anatomy of the Fasciocutaneous Branches of the First and Second Perforators Arteries in the Posterior Thigh Area
Authors: Calil José Augusto , Ferreira Lydia Masako , Filho José Laredo
Published: February 2017

The anatomy of the fasciocutaneous branches of the first and second perforators were studied to help elaborate a flap for use in the reconstruction of the gluteal and perineal regions. After dissecting 40 thighs in fresh cadavers, it was found that the fasciocutaneous branches of the first and second perforators were 1.21 mm and 1.01 mm in diameter, respectively. The distances from the first and second perforators to the greater trochanter of the femur were 6.23 cm and 12.19 cm, respectively. The cutaneous area nourished by each one of the arteries was evaluated through the injection of dye.
Applied Anatomy of the Inferior External Pudendal Artery
Authors: Cymrot Moacir , Ferreira Lydia Masako
Published: February 2017

The present study was conducted to assess the presence of the inferior external pudendal artery (IEPA), its diameter and course, and the cutaneous area nourished, and to support its use as an arterial pedicle in thigh flaps. Fifty thighs from 25 recent cadavers were dissected. IEPAs were found in 96% of the specimens, all arising from the femoral artery. Their average diameter was 1.4 mm, and the distance from point of origin to line ‘a’ averaged 5.6 cm. IEPAs appeared in front of the femoral vein in all cases and behind the great saphenous vein in 90% of cases. IEPAs ran medial and inferior courses, passing before the adductor magnus and pectineal muscles. Dye injection into the artery demonstrated that genital and anterosuperomedial areas of the thighs of the same side were nourished cutaneous territory. These anatomical characteristics of the IEPA support the raising of a septofasciocutaneous flap at the anterior superomedial aspect of the thigh.
Facial Rejuvenation: A Scarless Technique
Authors: Rai Kimit
Published: February 2017

A scarless facelift operation is the procedure of choice for facial rejuvenation. Emphasis is placed on the midfacial area to compliment the overall appearance of the face. Nasojugal folds are eliminated or improved. The cheek lift provides some augmentation in the malar area, which reduces the prominence of the nasolabial fold. Complications are minimal. The subperiosteal facelift operation is done via the lower eyelid blepharoplasty incision. Concurrent lower eyelid canthoplasty is done at the time of blepharoplasty to support the eyelid and to avoid postoperatiave ectropion.
Patellar complications in single versus double tunnel medial patellofemoral ligament reconstruction
Authors: Mohammed Riazuddin , Hunt Neil , Gibbon AJ
Published: February 2017

Purpose:

Hamstring graft fixation on the patellar side during medial patellofemoral ligament (MPFL) reconstruction is usually with transosseous tunnels and can frequently lead to further problems. The aim of our study was to compare and analyse patellar complications in single patellar tunnel versus double tunnel hamstring graft fixation.

Methods:

Twenty-nine knees with MPFL reconstructions (group S) in which the hamstring tendon graft was transfixed using a suspensory fixation method in a single tunnel drilled across the patella were analysed in comparison with 29 knees (group D) with interference fixation of the graft through two tunnels drilled up to a predetermined depth in the patella. Primary outcome measured was any patellar complication like anterior knee pain and patella fracture. Secondary outcomes assessed were future functional instability and failure of reconstruction.

Results:

Anterior knee pain was noted in six patients in group S, of which three patients had removal of the irritating metalwork on the patella. In all, nine surgical interventions were needed in six patients in this group. Three patients in group D complained of knee pain, but no one in this group needed any further surgical interventions ( p value 0.02). Symptomatic instability requiring revision surgery or realignment surgery was required in two patients in the group S and none in group D. No patellar fractures were seen in either group.

Conclusion:

Our study showed increasing problems with single tunnel patellar fixation, with more reoperation and failure rates compared to double tunnel fixation. The evidence supports the move towards anatomical double bundle MPFL reconstructions.
Tech-Check-Tech in Community Pharmacy Practice Settings
Authors: Frost Timothy P. , Adams Alex J.
Published: February 2017

Objective: The benefit of a tech-check-tech (TCT) practice model in institutional settings has been well documented. To date, few studies have explored TCT beyond institutional settings. This article summarizes the existing evidence in community pharmacy–based TCT research with respect to dispensing accuracy and pharmacist time devoted to direct patient care. Data Sources: A literature review was conducted using MEDLINE (January 1990 to August 2016), Google Scholar (January 1990 to August 2016), and EMBASE (January 1990 to August 2016) using the terms “tech* and check,” “tech-check-tech,” “checking technician,” and “accuracy checking tech*”. Bibliographies were reviewed to identify additional relevant literature. Study Selection and Data Extraction: Studies were included if they analyzed TCT and were conducted in a community pharmacy practice site, inclusive of chain, independent, mass merchant, supermarket, and mail order pharmacies. Studies were excluded if the TCT practice model was conducted in an institutional or long-term care setting. Survey data on theoretical models of TCT in community pharmacy practice settings were also excluded. Data Synthesis: Over the past 14 years, 4 studies were identified indicating TCT has been performed safely and effectively in community settings. The studies demonstrate that trained community technicians perform as accurately as pharmacists and that TCT increased the amount of pharmacist time devoted to clinical activities. In the 2 studies that reported accuracy rates, pharmacy technicians performed at least as accurately as pharmacists (99.445 vs 99.73%, P = .484; 99.95 vs 99.74, P < .05). Furthermore, 3 of the studies reported gains in pharmacist time, with increases between 9.1% and 19.18% of pharmacist time for consultative services. Conclusions: The present studies demonstrate that TCT can be safe and effective in community pharmacy practice settings, with results similar to those found in institutional settings. It is anticipated more states will explore TCT in community settings in the years ahead as a strategy to improve patient care.
Identification of an HLA class I allele closely involved in the autoantigen presentation in acquired aplastic anemia
Authors: Zaimoku Yoshitaka , Takamatsu Hiroyuki , Hosomichi Kazuyoshi , Ozawa Tatsuhiko , Nakagawa Noriharu , Imi Tatsuya , Maruyama Hiroyuki , Katagiri Takamasa , Kishi Hiroyuki , Tajima Atsushi , Muraguchi Atsushi , Kashiwase Koichi , Nakao Shinji
Published: February 2017

Key Points

Somatic mutations of HLA-B*40:02 are very frequently detected in granulocyte of patients with acquired aplastic anemia. Antigen presentation via HLA-B4002 may play a critical role in the pathophysiology of acquired aplastic anemia.
Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes
Authors: Dei Cas Alessandra , Spigoni Valentina , Cito Monia , Aldigeri Raffaella , Ridolfi Valentina , Marchesi Elisabetta , Marina Michela , Derlindati Eleonora , Aloe Rosalia , Bonadonna Riccardo C. , Zavaroni Ivana
Published: February 2017

Background

Fewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown.

Methods

Randomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34+/CD133+/KDR+/106 cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed.

Results

Baseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers.

Conclusions

V exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity.

Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013
Generalized α-nonexpansive mappings in Banach spaces
Authors: Shukla Rahul , Pant Rajendra , De la Sen Manuel
Published: February 2017

We consider a new type of monotone nonexpansive mappings in an ordered Banach space X with partial order ⪯. This new class of nonlinear mappings properly contains nonexpansive, firmly-nonexpansive and Suzuki-type generalized nonexpansive mappings and partially extends α-nonexpansive mappings. We obtain some existence theorems and weak and strong convergence theorems for the Mann iteration. Some useful examples are presented to illustrate the facts.
Disciplinary variations in academic promotional writing: the case of statements of purpose
Authors: Chen Sibo
Published: February 2017

This paper explores disciplinary variations in academic promotional writing via a comparative analysis of statements of purpose (SoPs) written for different disciplines. A total of 100 SoPs written by English as an additional language (EAL) applicants from mainland China were collected, which were drawn from five academic disciplines: business, engineering, humanities, science and social science. Following a corpus-driven research design, these SoP samples were analyzed in terms of their lexico-grammatical and rhetorical features. The data analysis suggests that although on the surface these SoP samples share similarities in lexico-grammatical and rhetorical features, they are quite different in terms of their preferred persuasion strategies. While SoPs written for engineering and science primarily base their self-promotional arguments upon the applicants’ previous research experiences and future research prospects, those written for business, humanities and social science tend to focus on how the applicants’ unique Chinese socio-cultural backgrounds would contribute to their desired programs. The above finding sheds light upon how academic genres are invariably embedded in disciplinary practices, with each discipline having its own communicative purposes, discourse community members, academic expectations and disciplinary constraints.
Fast inversion of logging-while-drilling resistivity measurements acquired in multiple wells
Authors: Bakr Shaaban A. , Pardo David , Torres-Verdín Carlos
Published: February 2017

We have developed a new method for the fast inversion of borehole resistivity measurements acquired in multiple wells using logging-while-drilling instruments. There are two key novel contributions. First, we approximate general 3D transversely isotropic (TI) formations with a sequence of several “stitched” 1D planarly layered TI sections. This allows us to approximate the solution of rather complex 3D formations using only 1.5D simulations. Second, the developed method supports the simultaneous inversion of measurements acquired in different neighboring wells and/or with different logging instruments. Numerical experiments performed with realistic 3D synthetic formations confirm the flexibility of the method and the reliability of the inversion products. The method yields relative errors of less than 5% on the model space, and it enables the interpretation of resistivity measurements acquired in multiple wells (e.g., an exploratory, an offset, and a geosteering well) and with any combination of coaxial and/or triaxial commercial logging measurements acquired with known antennae configurations. Numerical results also indicate that thinly bedded resistive formations are very sensitive to the presence of noise on the measurements and/or to possible errors on bed-boundary locations, whereas conductive layers are only weakly sensitive to those effects.
Methylglyoxal-bis(guanylhydrazone) (Methyl-GAG): current status and future prospects.
Authors: Warrell R P , Burchenal J H
Published: February 2017

Initial clinical trials of methyl-GAG (MGBG) showed that repetitive daily administration produced severe, occasionally fatal, toxic reactions. After two decades of neglect, recent studies have shown that doses of 500-600 mg/sq m administered every 7-14 days are very well tolerated. Moreover, current results indicate that MGBG has useful antitumor activity in patients with advanced malignant lymphoma and carcinomas of the head and neck, esophagus, and lung (non-small cell). The drug's mechanism of cytotoxic action and its toxic effects are not shared by most other cancer chemotherapeutic drugs. Furthermore, Phase II and Phase III evaluation are required to determine the therapeutic potential of this unique agent.
Alternating Combination Chemotherapy and Levamisole Improves Survival in Multiple Myeloma
Authors: Salmon Sydney E. , Haut Arthur , Bonnet John D. , Amare Mammo , Weick James K. , Durie Brian G. M. , Dixon Dennis O.
Published: February 2017

In the August issue of the Journal, the article by Salmon et al (1:453–461, 1983) contained an error. At the request of the authors, the title of the article should not have included mention of Levamisole, but rather should have read "Alternating Combination Chemotherapy Improves Survival in Multiple Myeloma: A Southwest Oncology Group Study,"
Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.
Authors: Jain K , Arlin Z , Mertelsmann R , Gee T , Kempin S , Koziner B , Middleton A , Jhanwar S , Chaganti R , Clarkson B
Published: February 2017

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.
Extralymphatic involvement in diffuse non-Hodgkin's lymphoma.
Authors: Paryani S , Hoppe R T , Burke J S , Sneed P , Dawley D , Cox R S , Rosenberg S A , Kaplan H S
Published: February 2017

Between 1961 and 1982, 543 patients with diffuse histiocytic, mixed, or undifferentiated lymphoma were treated at Stanford University, Stanford, Calif. Of this group, 281 (52%) had extralymphatic lesions and the 111 patients with stage IE and IIE disease were subjected to analysis. Most patients (94) had diffuse histiocytic lymphoma. Lymphangiography was performed in 77%, bone marrow biopsy in 91%, and diagnostic or staging laparotomy in 52% of the patients. All but five patients were treated with megavoltage irradiation and 35 patients received combination chemotherapy. Median follow-up was 4.0 years. Kaplan-Meier actuarial survival at five and 10 years was 46% and 36%, respectively. Freedom from relapse (FFR) at five years was 49% with no relapses beyond that point. The most common extralymphatic sites were the gastrointestinal tract, the head and neck region, and the lung. Prognosis could not be correlated with the specific sites of involvement. Patients with bulky disease (greater than 10 cm) or more than three sites of involvement had a significantly lower survival and FFR. There was no significant difference in outcome for patients treated with irradiation or combined modality therapy. Most patients (62%) relapsed in distant extralymphatic sites.
High-dose VP-16-213 and autologous bone marrow transplantation for refractory malignancies: a phase I study.
Authors: Wolff S N , Fer M F , McKay C M , Hande K R , Hainsworth J D , Greco F A
Published: February 2017

VP-16-213, a congener of epipodophyllotoxin, is a useful chemotherapeutic agent especially against small-cell carcinoma of the lung, germ cell carcinoma, and lymphoma. The standard dose of this drug is limited by myelosuppression. Autologous transplantation of cryopreserved bone marrow assures the restoration of hematopoiesis after marrow ablative cytotoxic therapy. By using this technique, VP-16-213 was dose-escalated using a Fibonacci scheme from the previous highest dose administered to humans (1,500 mg/m2) to 2,700 mg/m2 (900 mg/m2 per day for three consecutive days). At 2,700 mg/m2, severe extramedullary toxicity of the mucous membranes was observed in three of three courses. At the next highest dose (2,400 mg/m2), two of 18 courses (11%, p less than 0.01) resulted in severe mucositis, thus defining this dose as the maximally tolerated dose based on extramedullary toxicities. As anticipated, myelotoxicity was severe but based on the kinetics of marrow recovery, VP-16-213 in these doses appeared not to be marrow ablative. Based on responses observed in this study, high-dose VP-16-213 should be explored in phase II studies or used in combination chemotherapy.
Chemotherapy of refractory germ cell cancer with Etoposide.
Authors: Lederman G S , Garnick M B , Canellos G P , Richie J P
Published: February 2017

Eighteen patients with advanced germ-cell cancer (12 primary gonadal, six extragonadal) that was refractory to vinblastine (V), cisplatin (P), and bleomycin (B) were treated with Etoposide (VP-16-213) and cisplatin +/- bleomycin sulfate +/- doxorubicin hydrochloride. All patients experienced nausea, vomiting, alopecia, and myelosuppression. There were no treatment-related deaths. Five (42%) of 12 patients with primary gonadal germ-cell cancer achieved a complete remission and are presently alive with no evidence of disease. None of the six patients with extragonadal germ-cell cancer achieved a complete response. Thirteen patients died 6.2 months (median) after starting Etoposide treatment. Etoposide-containing chemotherapy is useful in patients with primary gonadal germ-cell cancer. Alternative therapies are needed for patients with extragonadal germ cell cancer.
Analysis of survival by tumor response.
Authors: Anderson J R , Cain K C , Gelber R D
Published: February 2017

The common practice of comparing the survival of responders and nonresponders when reporting the results of cancer chemotherapy treatment is investigated. The usual method of comparing responders and nonresponders is biased in favor of responders, and these results are frequently misinterpreted as providing evidence that response prolongs survival, or that the treatment under study is effective. Two valid methods for comparing responders and nonresponders are discussed and recommendations are made concerning the analysis of survival by response. A comparison of survival by response category may be useful descriptively, but such a comparison should not be used for inference concerning treatment effectiveness.
High-dose methotrexate as part of remission maintenance therapy for childhood acute lymphocytic leukemia: a Pediatric Oncology Group pilot study.
Authors: Frankel L S , Wang Y M , Shuster J , Nitschke R , Doering E J , Pullen J
Published: February 2017

Seventeen children with acute lymphocytic leukemia (ALL) in remission were treated with parenteral high-dose methotrexate (HDM) pulses every eight weeks during standard 6-mercaptopurine and methotrexate (MTX) oral maintenance therapy. MTX (1,000 mg/m2) was infused over one hour followed by one hour of intravenous hydration for the purpose of achieving plasma and cerebrospinal fluid (CSF) levels greater than 10(-6) M for a period of 24 hours. Leucovorin (15 mg/m2) was administered orally six, 12, and 18 hours after completion of the HDM. Plasma and CSF concentrations of MTX were evaluated serially in the first 48 hours. During the first 24 hours, the plasma MTX level was maintained at greater than 10(-6) M. The patients receiving intrathecal MTX at a dose of 15 mg/m2 had an adequate, sustained MTX level in the CSF, but when no intrathecal MTX was administered, the CSF levels were less than 10(-6) M. For that reason, intrathecal MTX in a low dose (6 mg/m2) was injected intrathecally one hour after the HDM infusion, allowing the MTX level in CSF to approximate 10(-6) M over the 24 hours. The toxicity of this therapy was minimal. Due to the facts that the plasma and CSF MTX levels could be sustained above the desired concentrations and this regimen could be given in the outpatient clinic, this program has been incorporated into an ongoing study in an effort to prolong complete remissions.
Karnofsky Memorial Lecture. Breaking the cure barrier.
Authors: Holland J F
Published: February 2017

Breaking the cure barrier is a biologic and a conceptual problem that has already been accomplished for several tumors. It is helpful to consider neoplasms in mathematical terms as many-celled tumors (polycytomas: kilocytomas, megacytomas, gigacytomas, and teracytomas). A new chemotherapeutic taxonomy recognizes curable, subcurable, and precurable cancers each with definable characteristics. A simplified technique of recognizing early cures is described by calculating the probability that an interruption in an exponential failure slope occurred by chance. Examples of cures of acute myelocytic leukemia, of superior chemotherapy for Hodgkin's disease in young adults, and of superior adjuvant chemotherapy for breast cancer are given. The interaction of surgery with chemotherapy is illustrated in pure form in acute myelocytic leukemia and in ovarian cancer. Curative chemotherapy is closer at hand than is generally believed. Nomograms for cure prediction are presented as inducements to contemplate curative approaches to cancer therapy.
Randomized study of cyclophosphamide, doxorubicin, and etoposide (VP16-213) with or without cisplatinum in non-small cell lung cancer.
Authors: Fuks J Z , Aisner J , Van Echo D A , Schipper H , Levitt M , Ostrow S , Wiernik P H
Published: February 2017

Sixty-eight patients with non-small cell lung cancer were treated in a prospectively randomized study with cyclophosphamide, doxorubicin (Adriamycin), and etoposide (VP16-213) with cisplatinum (CAE +/- P). Response rate, time to progression, and survival of CAE-P treated patients were each superior compared to those of patients who received CAE therapy. Of 36 patients, 10 (4 complete remissions, 6 partial remissions) responded to CAE-P and of 29 patients 3 (1 complete remission, 2 partial remissions) responded to CAE (p = 0.073). The median time to treatment failure was 22.9 wk for the CAE-P regimen and 15.0 wk for CAE (p = 0.032). The median survival for patients treated on the regimen with and without cisplatinum was 34.5 and 22.5 wk, respectively (p = 0.04). There were two CAE-P and one CAE drug-related deaths. Toxic effects were more severe in the CAE-P regimen. The addition of cisplatinum to the CAE combination produced an increase in response rate with significant prolongation in both time to progression and survival, but did add morbidity. These results suggest that the combined use of cisplatinum with at least one of the chemotherapeutic agents in the CAE regimen is synergistic.
End results of treating children with localized non-Hodgkin's lymphomas with a combined modality approach of lessened intensity.
Authors: Murphy S B , Hustu H O , Rivera G , Berard C W
Published: February 2017

From 1978 to 1982, 28 children with localized non-Hodgkin's lymphomas, stages I and II, were treated with a combined modality protocol, reduced in intensity in comparison to our previous institutional protocol (1975-1978, reported in Cancer 45: 630-637, 1980), and modest by comparison to many current intensive regimens in widespread use. Induction consisted of vincristine (6 weekly doses, 1.5 mg/m2), cyclophosphamide (3 doses, on days 0, 21, and 42, 600 mg/m2 IV), and oral prednisone (40 mg/m2, daily for 1 mo) combined with low-dose, involved-field, supervoltage radiotherapy (2000 rads). Prophylactic treatment of the central nervous system was not given to all children, but only to those with primary tumors in the head and neck region, and consisted of intermittent intrathecal methotrexate only (12 mg/dose, three times in induction, and subsequently every 6 wk). Maintenance therapy, consisting of oral daily 6-mercaptopurine (75 mg/m2) and oral weekly methotrexate (30 mg/m2), was continued for a total duration of 15 mo from diagnosis. Overall, there were 15 children with stage I and 13 with stage II disease, and the majority of the cases (17 of 28) were localized to the head and neck. In addition, 7 children, all stage II, had completely resected gastrointestinal tumors; the other 4 cases presented in inguinal nodes. Histologically, 27 of the 28 tumors were high-grade diffuse (13 undifferentiated, i.e., small noncleaved cell type; 11 histiocytic, i.e., 5 large noncleaved cell type, and 6 immunoblastic type; and 3 lymphoblastic type); 1 case was mixed cell type, nodular and diffuse. All children were judged to be in complete remission at the end of induction, and 24 of 28 (85.7%) remain free of disease 4+ mo to nearly 4 yr from diagnosis (median 24+ mo); 19 have completed all planned therapy and are in unmaintained remission. The 4 cases failing therapy all were characterized by diffuse undifferentiated (small noncleaved cell) histology and exhibited regrowth of local tumor, resulting in a failure rate for this group (4 of 13, 30%) significantly different than for all remaining cases of other histologies (0 of 15), p less than 0.02 by log rank analysis. Patient tolerance to therapy was excellent, with negligible acute toxicity, and ambulatory outpatient management was the norm. Long-term follow-up will be necessary to judge whether adverse late consequences of treatment have been reduced by this approach. We conclude that a reduction in the intensity of therapy for children with stage I and II non-Hodgkin's lymphomas is feasible, apparently without significantly jeopardizing their excellent chance for cure.
Phase I trial of retinol in cancer patients.
Authors: Goodman G E , Alberts D S , Earnst D L , Meyskens F L
Published: February 2017

Vitamin A (all-trans-retinol) and its analogues are undergoing evaluation as antineoplastic and chemoprevention agents. Because its toxicity and activity are poorly defined, we have completed a phase I trial of retinol. Retinol was administered to 13 cancer patients in daily doses ranging from 100,000 units/m2 to 350,000 units/m2. Neuropsychiatric changes were the earliest dose-limiting symptomatic toxicities, noted in 3 of 5 patients receiving more than 240,000 U/m2 for 3-4 months. Two patients receiving more than 270,000 U/m2 developed hepatomegaly after 3 and 4 months. Liver biopsies were consistent with vitamin A toxicity. Three patients receiving 200,000 U/m2 developed an increase in serum triglycerides concentration. Mild skin and mucous membrane dryness occurred in most patients receiving more than 150,000 U/m2. A mixed response was seen in one patient with melanoma. Because of neuropsychiatric and hepatic toxicity a retinol dose of 200,000 U/m2/day is recommended for future phase II trials.
Cisplatin-vincristine-bleomycin therapy in squamous cell carcinoma of the head and neck.
Authors: Amrein P C , Fingert H , Weitzman S A
Published: February 2017

Seventy patients with squamous cell carcinoma of the head and neck were treated with a 24-hour infusion of cisplatin, followed by vincristine and bleomycin. Among 37 patients with no prior treatment who had stage III (2) or stage IV (35) disease, there were 2 complete responders and 23 with a partial response, for an overall response frequency of 67%. Among 27 patients with recurrent disease after radiotherapy and/or surgery, there were 9 (33%) partial responses. Among 6 patients having failed prior chemotherapy, there was 1 complete responder, still in remission at 26 months. Response frequency was highly dependent on performance status and stage of disease, with a response of 80% in the 0 performance status group and 83% for stages less than T4N3M0. Among 18 patients with resectable disease, 51% remain disease-free at 12 months with an overall median survival at 16 months. Among the 33 patients with recurrent disease, the median duration of response and survival was 4 and 12 months for responders, respectively; nonresponders had a median survival of 5 months. The toxicity of this regimen was generally mild, with 21% of patients having no vomiting and 91% never having a serum creatinine over 2.0 mg/dL. There were 2 cases of pulmonary fibrosis. This chemotherapy regimen compares favorably with other published regimens for head and neck cancer with respect to activity and may be less toxic.
Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease.
Authors: Tannir N , Hagemeister F , Velasquez W , Cabanillas F
Published: February 2017

Thirty-six consecutive patients with advanced recurrent Hodgkin's disease resistant to chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) were treated with doxorubicin (Adriamycin), bleomycin, (dacarbazine) DTIC, (lomustine) CCNU, and prednisone (ABDIC). Among the 34 patients evaluable for response, complete remission occurred in 35% and partial remission in 35%. The achievement of complete remission during primary MOPP induction was a statistically significant prognostic factor that predicted complete remission with ABDIC (p less than 0.01). The median time to complete remission was 2 months (range 1-11 mo). The median relapse-free survival time for complete responders is 47 months, and an estimated 53% of all patients who achieve complete remission are projected to be alive, free of disease off therapy at 3 years from initiation of ABDIC. The median survival of all patients is 24 months. The median survival of complete responders, partial responders, and nonresponders is 70, 17, and 4 months, respectively. The survival curve for complete responders is significantly different from that for partial responders (p less than 0.01); the survival curve for partial responders is also significantly different from that of nonresponders (p less than 0.01). Toxicity of ABDIC was acceptable; only one patient died from complications of myelosuppression. Our results indicate that ABDIC is a potentially curative regimen for a fraction of patients with MOPP-resistant Hodgkin's disease who achieve complete remission with prior MOPP therapy. It also prolongs the survival of patients who do not achieve complete remission with prior MOPP therapy.
Second central nervous system prophylaxis in children with acute lymphoblastic leukemia who relapse after elective cessation of therapy.
Authors: Rivera G , George S L , Bowman W P , Kalwinsky D , Ochs J , Dahl G V , Hustu H O , Simone J V
Published: February 2017

A treatment plan to achieve better disease control in patients with acute lymphoblastic leukemia (ALL) who relapse after elective cessation of therapy was assessed. The principal modifications were (1) a second preventive treatment of the central nervous system (CNS) at relapse and every six weeks throughout therapy, using intrathecal methotrexate with cytosine arabinoside, and (2) a four-week course of systemic chemotherapy given immediately before therapy was stopped a second time. Twenty-four patients were studied. There have been no meningeal relapses, in contrast to seven among 16 similar patients who were retreated without CNS prophylaxis. Although the median length of second hematologic remission was not significantly different from the outcome in the comparison group, a much higher proportion of patients (eight of 24 versus zero of 17) remain in prolonged reinduced complete remission (48-79 months). Children whose first relapse occurred later than six months after cessation of therapy had significantly longer subsequent remissions. These end results establish the value of intrathecal CNS prophylaxis in relapsed ALL and suggest that a late intensive phase of therapy will extend remissions in a substantial proportion of patients.
Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer.
Authors: Kinsella T J , Mitchell J B , Russo A , Aiken M , Morstyn G , Hsu S M , Rowland J , Glatstein E
Published: February 2017

Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 X 10(-7) mol/L and 1 X 10(-6) mol/L during infusion of 650 and 1,000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1,000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). We conclude that local and systemic toxicity of continuous infusion of BUdR at 1,000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with our previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.
Monoclonal antibody therapy of malignant melanoma: in vivo localization in cutaneous metastasis after intravenous administration.
Authors: Oldham R K , Foon K A , Morgan A C , Woodhouse C S , Schroff R W , Abrams P G , Fer M , Schoenberger C S , Farrell M , Kimball E
Published: February 2017

The murine antimelanoma monoclonal antibody, 9.2.27, was administered intravenously to eight patients with metastatic malignant melanoma. Biopsies of metastatic nodules clearly demonstrate the selective localization of this antibody on the melanoma cell surface with a dose-response relationship to the quantity of administered antibody. The antibody infusions were clinically well tolerated and the pharmacokinetics of the antibody and the antiglobulin responses are described. This study indicates that murine monoclonal antibodies have potential as selective targeting agents in the design of future therapeutic trials using monoclonal antibodies or conjugates thereof in the treatment of cancer.
Ethiodized oil emulsion 13 in computed tomography of hepatoma.
Authors: Dutcher J P , Haney P J , Whitley N O , Finley R , Pearl P , Didolkar M S , Wiernik P H
Published: February 2017

Six patients with biopsy-proven hepatoma were prospectively evaluated both by conventional computed tomography (CT) and by scans using ethiodized oil emulsion 13 (EOE 13) as a contrast agent. EOE 13 infusion resulted in marked improvement in the demonstration of the neoplasm in all cases and allowed more accurate definition of tumor extent than was possible with standard scanning techniques. In two cases EOE 13 enhancement was essential for complete radiographic depiction of tumor location, size, and extent. EOE 13 also proved to be of considerable value in assessment of therapeutic response in three patients, permitting more objective determination of tumor growth or regression. EOE 13--enhanced CT scanning provides a valuable means of staging patients presenting with hepatoma and is a reliable, accurate means of radiographic follow-up.
Polar solvents: a novel class of antineoplastic agents.
Authors: Spremulli E N , Dexter D L
Published: February 2017

It has been known for many decades that certain murine and human cancers can spontaneously mature to benign tissue. These observations have stimulated investigators to attempt to induce a state of more normal or benign differentiation in cancer cells using biologic substances or chemicals. Polar solvents including dimethylsulfoxide, dimethylformamide, and monomethylformamide have proven to be good inducers of maturational events in murine and human cancer cells. Moreover, several laboratories have demonstrated that polar solvents inhibit the growth of human tumor xenografts in nude mice. These findings have resulted in the entry of monomethylformamide into phase I clinical trials in America and Europe. Preclinical work further suggests that polar solvents may be useful agents in combination with conventional treatment modalities. The use of drugs such as monomethylformamide that can convert neoplastic cells to benign cells rather than kill the tumor cells represents an important conceptual departure from standard cytotoxic chemotherapy. The use of maturational-agent therapy should be considered as an important new development in the design of cancer treatment protocols.
Clinical features and results of management of superior vena cava syndrome secondary to lymphoma.
Authors: Perez-Soler R , McLaughlin P , Velasquez W S , Hagemeister F B , Zornoza J , Manning J T , Fuller L M , Cabanillas F
Published: February 2017

Thirty-six of 915 patients with non-Hodgkin's lymphoma presented with superior vena cava syndrome (SVCS). The histologic types associated with SVCS were diffuse large cell in 23 patients, lymphoblastic in 12, and follicular large cell in one patient. Radiotherapy alone appeared equal to chemotherapy alone or in combination with radiotherapy in achieving relief of SVCS symptoms. Chemotherapy alone or in combination with radiotherapy was superior to radiotherapy alone in prolonging relapse-free survival and overall survival. No differences in relapse-free survival and survival were found between the patients treated with chemotherapy alone and those treated with chemotherapy and radiotherapy, but the addition of radiotherapy appeared to prevent local relapses in the group with large-cell lymphoma. The presence of symptoms of involvement of other mediastinal structures such as dysphagia, hoarseness, or stridor (DHS), a higher grade of intensity, and a shorter duration of symptoms (less than or equal to 2 weeks) appeared to adversely influence relapse-free survival and survival. The following conclusions were made: (1) a histologic diagnosis before the onset of treatment is desirable and feasible in patients presenting with SVCS except in those with severe respiratory distress, (2) both chemotherapy and radiotherapy are equally effective in alleviating the symptoms of SVCS, and (3) combined modality treatment with chemotherapy and radiotherapy results in a lower frequency of local relapses compared to chemotherapy alone but survival was similar in both groups.
Relationships of body size with breast cancer.
Authors: Kalish L A
Published: February 2017

Three measures of body size (weight, height, and obesity) were compared with other patient characteristics in 852 operable node-positive breast cancer patients (age, 25-74 years) newly diagnosed in the United States. Weight and obesity were significantly associated with number of positive nodes. In postmenopausal women, weight and obesity were weakly associated with estrogen receptors. Observed weight and height distributions were compared with national averages and found to be highly aberrant in older women. There was an excess of tall woman (greater than or equal to 66 inches) among the study group in all age groups. An excess of heavy women (greater than or equal to 140 pounds) among the study group was observed only in the 55-74 years age group.
Randomized phase III comparison of three doxorubicin-based chemotherapy regimens in advanced non-small cell lung cancer: a Southeastern Cancer Study Group trial.
Authors: Robert F , Omura G A , Birch R , Krauss S , Oldham R
Published: February 2017

From 1978 to 1981, 537 patients with advanced non-small cell lung cancer were randomly assigned to three regimens containing cyclophosphamide and doxorubicin alone or in combination with methotrexate or cisplatin. Eligible patients had measurable disease and had no prior exposure to chemotherapy. Of the patients entered on the study, 505 were evaluable for toxicity and 488 were evaluable for response. The overall response rate (complete and partial responses) was only 9%. Response rates did not vary significantly with respect to treatment regimen, histologic subtypes, extent of disease, or performance status. There was no survival advantage for any regimen. The major toxicities were myelosuppression and nausea-vomiting. These doxorubicin-based chemotherapy regimens produced disappointing results in patients with advanced non-small cell lung cancer. A search for more active antitumor agents in lung cancer is necessary.