bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Adrenaline Injection Injuries: A Case Series and Review
Authors: Elmaraghy MW , Elmaraghy AW , Evans HB
Published: February 2017

MW ElMaraghy, AW ElMaraghy, HB Evans. Digital adrenaline injection injuries: A case series and review. Can J Plast Surg 1998;6(4):196-200.

Accidental digital adrenaline autoinjection is an uncommon injury, with only a few case reports existing in the literature. A six-case series of digital EpiPen injection injuries, a review of the literature and treatment protocols with their pathophysiological and pharmacological basis are presented. Oral nifedipine, topical 2% nitroglycerine paste, digital block using lidocaine and warm water immersion are ineffective in acutely reversing digital ischemia. Clinical and experimental evidence demonstrating spontaneous resolution of digital vasospasm may support the expectant management of these injuries. If medical intervention is undertaken, safe and rapid reversal of adrenaline-induced digital ischemia can be achieved with local and/or regional infiltration of phentolamine mesylate. Based on a review of the current case series and the literature, the authors’ preferred method of treatment includes simultaneous digital block with a mixture of phentolamine and 2% lidocaine and local injection of phentolamine at the puncture site. Initially, the authors suggest using 5 mg phentolamine mesylate in 2 mL of 2% lidocaine, and injecting 1 mL (2.5 mg) of the solution into the ulnar and 1 mL (2.5 mg) into the radial aspect of the base of the involved digit, followed by injecting the injury site with a 5 mg/mL solution of phentolamine.
Postoperative Drainage Is Recommended in Ulnar Nerve Transposition
Authors: Deune E Gene , Mackinnon Susan E
Published: February 2017

EG Deune, SE Mackinnon. Postoperative drainage is recommended in ulnar nerve transposition. Can J Plastic Surg 1998;6(4):201-203.

Surgery to transpose the ulnar nerve is a common treatment for cubital tunnel syndrome. Postoperative hematoma is a rare, but well recognized complication of this surgery, whereas postoperative bruising is a common sequela. A retrospective review of 138 cases of anterior submuscular transposition performed between December 1991 and December 1995 was conducted to evaluate the merits of postoperative drainage. Various parameters (patient, surgical, and anesthetic) were compared to determine their effect on drainage. Males had a higher postoperative drainage volume than females (P<0.0001). Other patient, surgical and anesthetic factors did not correlate significantly with the drainage volume. The mean drainage during the first postoperative day was 41.2±2.5 mL (range 3 mL to 190 mL). This volume is significant and warrants drainage with an indwelling catheter when anterior submuscular transposition of the ulnar nerve is performed.
Minimally Invasive Endoscopic Technique of Harvesting Free Gracilis Muscle Flap to Lower Donor Site Morbidity: A Feasibility Study in Cadavers
Authors: Mohammad Jamal A , Shenaq Saleh M
Published: February 2017

Endoscopic mobilization and harvesting of the gracilis muscle for free transfer applications and the versatility of this method are discussed in this report. This procedure was performed in 12 fresh human cadaver limbs (from six cadavers) to master the surgical technique for future clinical applications. Through two separate 2 cm incisions, one placed proximally and one distally along the axis of the muscle, the endoscope allowed the gracilis muscle and its related anatomical structures to be viewed, particularly the dominant vascular pedicle. The muscle flap, along with its vascular pedicle and motor nerve, were successfully harvested with the aid of endoscopy. The potential clinical advantages of endoscopically harvesting the gracilis muscle flap include shortening of the size of the surgical scar, relief of postoperative pain and hastened recovery of function.
Open Rhinoplasty for Correction of the Secondary Nasal Deformity Due to the Marcks Triangular Flap Cleft Lip Repair
Authors: Hallock Geoffrey G
Published: February 2017

The Marcks Z-plasty modification of the Tennison triangular flap cleft lip repair results in excellent preservation of the Cupid's bow, but in more severe clefts this technique is stigmatized by a characteristic V-shaped nasal rim deformity. This has proven extremely difficult to correct secondarily. An open rhinoplasty technique is advocated because superior exposure is essential to visualize deficient components, as well as the malformed lower lateral cartilage, which is a direct result of this lip repair. Nevertheless, typical results remain substandard in terms of achieving nasal symmetry as opposed to routine use of the Millard rotation-advancement repair, with or without primary nasal correction.
Buffalo Hump and HIV-1 Infection: Current Concepts and Treatment of a Patient with the Use of Suction-Assisted Lipectomy
Authors: Peters Walter , Phillips Anne
Published: February 2017

Human immunodeficiency virus (HIV) - 1 infection, or its treatment with protease inhibitors, may be associated with abnormal fat deposition. One or more of several areas may be affected, including the dorsal-cervical fat pad (‘buffalo hump’), abdominal region (‘protease paunch’, ‘crixbelly’), breasts or as a generalized lipomatosis. Fat accumulation is most common in the dorsal cervical and the abdominal areas. Only a relatively small number of patients have been studied, therefore, the true incidence of this accumulation is not known. The present study describes an HIV-1-infected man who developed a very large buffalo hump after treatment with indinavir who was successfully treated using tumescent suction-assisted lipectomy. This is the first published report of a buffalo hump treated using this modality.
Vein Donor Site Morbidity after Coronary Bypass Surgery: An Overlooked but Important Issue
Authors: Hallock Geoffrey G
Published: February 2017

Leg morbidity after harvest of veins for coronary artery bypass grafts (CABG) is a significant and under-recognized problem. Although it is not usually life-threatening compared with mediastinal wound infections, the absolute number of limb complications reported annually in North America is approximately double the rate of sternal wound infections. A review of the data in the Cardiac Registry at The Lehigh Valley Hospital (Allentown, Pennsylvania) for 4880 CABG patients from the past five years showed that sternal infections occurred in 48 patients (1%) compared with a reported lower limb morbidity in 31 (0.6%) hospitalized patients. This substantiates the point that morbidity is an important problem, especially if limb-threatening. Whereas many surgical protocols have been established for the treatment of mediastinal infections, there has been virtually no discussion on the management of the problematic donor limb. Plastic surgery consultation in this hospital was requested for only five (16%) patients with leg wounds, whereas it was the norm for the majority of sternal wounds (42 [87.5%]). Minimal debridement and expectant healing was the most common approach for these lower extremity wounds. An acceptable vascular profile in these patients, who often have coexistent atherosclerotic peripheral vascular disease, should be an initial priority. In those with limb complications, this had often been overlooked preoperatively. Because the failure of a wound to heal can result in limb amputation, early intervention by plastic surgeons must be emphasized.
Cubital Tunnel Syndrome – Endoscopic-Assisted Anterior Submuscular Transposition of the Ulnar Nerve: A Feasibility Study Using a Cadaver Model
Authors: Mohammad Jamal A , Hasaniya Nahidh , Shenaq Saleh M
Published: February 2017

The purpose of this project was to perform endoscopic-assisted release of the ulnar nerve with submuscular transposition using a single 4 cm incision at the cubital tunnel level in fresh cadaver limbs. A successful cubital tunnel release decompression depends on the precise release of all potential entrapment points. Twelve fresh cadaver limbs (from six human cadavers) were used for this project. A 4 cm incision was made along the course of the ulnar nerve at the cubital tunnel. While the ulnar nerve was under constant magnified visualization and protection, all surrounding fascial tissues were released freely from the nerve. The medial intermuscular septum and arcade of Struthers were adequately visualized and divided. The overlying superficial fascia of flexor carpi ulnaris being dissected freely from the nerve, the nerve was transposed and repair of the flexor aponeurosis to the medial epicondyle was completed. Release of the ulnar nerve with submuscular transposition was accessible through one small skin incision with the aid of the endoscope. This new procedure may have clinical applications with a surgical outcome similar to the traditional approach. This technique prevents long scarring, decreases patient postoperative pain and shortens the rehabilitation period.
Leg Salvage in An Elderly Patient with a Circumferential Avulsion
Authors: Nickerson Duncan , Taylor Christopher , Carr Nicholas
Published: February 2017

The present paper reports the case of an elderly woman who sustained an extensive lower extremity skin avulsion injury. Limb salvage was achieved by using split-thickness skin grafts that were harvested from the avulsed skin. The case is noteworthy because of the advanced age of the patient, the extent of the injury, the method of back-table skin graft harvest and the successful outcome.
Use of Google Scholar public profiles in orthopedics
Authors: Tetsworth Kevin , Fraser Dave , Glatt Vaida , Hohmann Erik
Published: February 2017

Introduction:

The purpose of this study was to survey the growth of Google Scholar public profiles in orthopedics over a 12-month period and to investigate global patterns.

Methods:

Data was prospectively acquired from June 2013 to June 2014. Google Scholar queries specific to orthopedic surgery were performed at 90-day intervals. Demographic aspects of each user were also compiled, including gender, current location, and primary interests. To determine differences between the growth of Google Scholar public profile registrations and citation counts, as well as differences in growth in different regions, repeated measures of analysis of variance (RMANOVA) were used.

Results:

RMANOVA revealed statistically significant differences ( p = 0.0001) for regional growth. The largest growth was observed in the United Kingdom ( p = 0.009, 289%), followed by the Asia-Pacific region ( p = 0.004, 177%) and “Other” ( p = 0.006, 172%). The mean growth per 90-day interval is 19.9% ( p = 0.003) and the mean 12-month growth is 107% ( p = 0.05). Statistically significant differences between gender (male vs. female) and basic and clinical sciences ( χ2 = 22.4, p = 0.0001) were observed.

Conclusion:

This study suggests an exponential growth in the number of authors in the field of orthopedic surgery creating a Google Scholar public profile, and at the current rate participation doubles every 10.6 months.
Is neck massage safe? A rare case of tetraplegia and spinal shock after neck manipulation
Authors: Ling Tan Han , Zakaria Amir Fariz Bin , Abdullah Ahmad Tajuddin Bin
Published: February 2017

Neck manipulation is associated with spinal cord injury. However, occurrence of such cases is infrequent. This article presents a 33-year-old gentleman who sustained acute tetraplegia after neck manipulation. The aim of this case report is to create awareness that vigorous neck manipulation could cause injury to the spinal cord.
Visible glove perforation in total knee arthroplasty
Authors: Jid Lee Qunn , Ping Mak Wai , Chung Wong Yiu , Leung Wai Yuk
Published: February 2017

Purpose:

The risk of superficial surgical site infection (SSI) and periprosthetic joint infection (PJI) after glove perforation is not evident. This study was to identify risk factors for glove perforation in primary TKR (total knee replacement) and the risk of subsequent superficial SSI and PJI.

Methods and materials:

Results of visible glove perforation of both inner and outer gloves during TKR were reviewed. A case–control analysis was performed on the preoperative and operative variables to identify predictive risk factors for glove perforation. Rate of SSI and PJI was compared between perforation and non-perforation groups, including 1226 series and 183 case–control subset.

Results:

One thousand two hundred twenty-six primary TKR from 2011 to 2014 was reviewed. Fifty-five knees had visible glove perforations. The operation perforation rate was 4.5%. Risk factors identified were body mass index (BMI) > 30, bilateral surgery, operation time >120 min and non-trainee surgeons. Superficial SSI was significantly higher in glove perforation group (9.15 vs. 0.51% and 0.55%). PJI was not significantly different (1.82% vs. 0.60% and 1.1%). The adjusted odds ratio for superficial SSI after perforation was 15.2, independent of BMI and operation time.

Conclusion:

Visible glove perforation in TKR is associated with several risk factors. The risk of superficial SSI is higher after perforation.
High-Grade Partial and Retracted (<2 cm) Proximal Hamstring Ruptures
Authors: Piposar Jonathan R. , Vinod Amrit V. , Olsen Joshua R. , Lacerte Edward , Miller Suzanne L.
Published: February 2017

Background:

High-grade partial proximal hamstring tears and complete tears with retraction less than 2 cm are a subset of proximal hamstring injuries where, historically, treatment has been nonoperative. It is unknown how nonoperative treatment compares with operative treatment.

Hypothesis:

The clinical and functional outcomes of nonoperative and operative treatment of partial/complete proximal hamstring tears were compared. We hypothesize that operative treatment of these tears leads to better clinical and functional results.

Study Design:

Case series; Level of evidence, 4.

Methods:

A retrospective review identified patients with a high-grade partial or complete proximal hamstring rupture with retraction less than 2 cm treated either operatively or nonoperatively from 2007 to 2015. All patients had an initial period of nonoperative treatment. Surgery was offered if patients had continued pain and/or limited function refractory to nonoperative treatment with physical therapy. Outcome measures were each patient’s strength perception, ability to return to activity, Lower Extremity Functional Scale (LEFS) score, Short Form–12 (SF-12) physical and mental component outcome scores, distance traversed by a single-leg hop, and Biodex hamstring strength testing.

Results:

A total of 25 patients were enrolled in the study. The 15 patients who were treated nonoperatively sustained injuries at a mean age of 55.73 ± 14.83 years and were evaluated 35.47 ± 30.35 months after injury. The 10 patients who elected to have surgery sustained injuries at 50.40 ± 6.31 years of age ( P = .23) and were evaluated 30.11 ± 19.43 months after surgery. LEFS scores were significantly greater for the operative group compared with the nonoperative group (77/80 vs 64.3/80; P = .01). SF-12 physical component scores for the operative group were also significantly greater ( P = .03). Objectively, operative and nonoperative treatment modalities showed no significant difference in terms of single-leg hop distance compared with each patient’s noninjured leg ( P = .26) and torque deficit at isokinetic speeds of 60 and 180 deg/s ( P = .46 and .70, respectively).

Conclusion:

Patients who undergo operative and nonoperative treatment of high-grade partial and/or complete proximal hamstring tears with <2 cm retraction demonstrate good clinical and functional outcomes. In our series, 40% of patients treated nonoperatively with physical therapy went on to have surgery. For those patients with persistent pain and/or loss of function despite conservative treatment, surgical repair is a viable treatment option that is met with good results.
A Pilot Randomized Controlled Clinical Trial to Assess Tolerance and Efficacy of Navy Bean and Rice Bran Supplementation for Lowering Cholesterol in Children
Authors: Borresen Erica C. , Jenkins-Puccetti NaNet , Schmitz Katie , Brown Dustin G. , Pollack Austin , Fairbanks Amanda , Wdowik Melissa , Rao Sangeeta , Nelson Tracy L. , Luckasen Gary , Ryan Elizabeth P.
Published: February 2017

Background: Navy beans and rice bran demonstrate efficacy to regulate serum cholesterol in hypercholesterolemic adults; however, the cardiovascular disease (CVD) protective properties of these foods in children are unknown and merit investigation. Objective: The objectives were to determine whether cooked navy bean powder (NBP) and/or heat-stabilized rice bran (RB) supplementation is tolerable, improves dietary fiber intake in children, and modulates lipid profiles. Methods: Children aged 8 to 13 years at risk for CVD due to abnormal lipids were recruited. Elevated cholesterol levels were defined as total cholesterol ≥180 mg/dL and high-density lipoprotein (HDL) <60 mg/dL; low-density lipoprotein (LDL) ≥100 mg/dL and HDL <60 mg/dL; or non-HDL >100 mg/dL and HDL <60 mg/dL. Participants completed a pilot 4-week, randomized controlled, 4-arm dietary intervention. They consumed study-provided muffins or a smoothie daily that included 0 g NBP or RB (control), 17.5 g NBP, 15 g RB, or a combination 9 g NBP + 8 g RB. Fasting blood was collected at baseline and week 4. Participants also completed 3-day food logs and gastrointestinal health questionnaires. Results: Thirty-eight children completed the trial (n = 9 control, n = 10 NBP, n = 9 RB, and n = 10 NBP + RB groups). Only 3 participants withdrew due to noncompliance of required food consumption. Participants in the intervention groups significantly increased intake of NBP and RB at week 4 (p≤.01). The NBP and NBP + RB groups increased total fiber intake from baseline to week 4 (p=.02 and p=<.01, respectively). HDL-cholesterol was higher in NBP-group participants compared to control at week 4 ( P = .02). Conclusion: Increasing NBP and/or RB intake is tolerable for children, and our findings suggest higher daily intakes are needed for a longer duration to induce favorable changes across multiple serum lipid parameters.
Reducing sedentary time and fat mass may improve glucose tolerance and insulin sensitivity in adults surviving 6 months after stroke: A phase I pilot study
Authors: Borschmann Karen N , Ekinci Elif I , Iuliano Sandra , Churilov Leonid , Pang Marco YC , Bernhardt Julie
Published: February 2017

Introduction

Deranged glycaemic control is common post-stroke, increasing risks of recurrent stroke and development of diabetes. The aim of the study is to examine glucose metabolism in relation to body composition, physical activity and sedentary time post-stroke.

Patients and methods

Observational study: Non-diabetic adults, unable to walk independently, were recruited within 2 weeks of first stroke. Primary outcome: 2-h glucose level (mmol/l, oral glucose tolerance test), assessed at baseline and 6 months. Homeostasis Model Assessment of Insulin Sensitivity, total body fat and lean mass (dual energy X-ray absorptiometry), sedentary time (lying or sitting), standing and walking (PAL2 accelerometer) were assessed at baseline, 1, 3 and 6 months. Generalised estimating equations were used to examine change over time and associations between outcome measures.

Results

Thirty-six participants (69.5 years (standard deviation 11.7), 13 (36.1%) female, moderate stroke severity (National Institute of Health Stroke Scale 11.5 (interquartile range 9.75, 16)). Within 6 months, adjusting for age and National Institute of Health Stroke Scale, every month 2-h glucose reduced by 4.5% ( p < 0.001), Homeostasis Model Assessment of Insulin Sensitivity improved 3% ( p = 0.04) and fat mass decreased 490 g (95% confidence interval 325, 655; p = 0.01). For every extra kilogram of body fat, 2-h glucose increased by 1.02 mmol/L (95% confidence interval 1.01, 1.02; p = 0.001); Homeostasis Model Assessment of Insulin Sensitivity reduced by 0.98% (95% confidence interval 0.97, 0.99; p = 0.001). Time spent sedentary reduced from 98.5% of measurement period (interquartile range 94.3, 99.8) to 74.3% (interquartile range 65.5, 88.6), by 2.8% monthly (95% confidence interval 1.8, 3.9, p < 0.001). For every additional 5% sedentary time, 2-h glucose increased by 1.05 mmol/L (95% confidence interval 1.04, 1.07; p < 0.001).

Conclusion

Reducing sedentary time and fat mass within 6 months of stroke may improve glucose tolerance and insulin resistance.
A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation
Authors: Ott Christian , Jumar Agnes , Striepe Kristina , Friedrich Stefanie , Karg Marina V. , Bramlage Peter , Schmieder Roland E.
Published: February 2017

Background

The sodium–glucose cotransporter 2 inhibitor, dapagliflozin, has been shown to improve diabetic control and reduce blood pressure in patients with type 2 diabetes mellitus. Its effects on micro- and macrovascular structure and function have not yet been reported.

Methods

This was a prospective, single-centre, placebo-controlled, double-blind, randomised crossover phase IIIb study conducted between March 2014 and February 2015. After a 4-week run-in/washout phase, patients (N = 59) received 6 weeks of either dapagliflozin 10 mg or placebo once daily. They then underwent a 1-week washout before crossing over to the other treatment. Changes in retinal capillary flow (RCF) and arteriole remodelling were evaluated using scanning laser Doppler flowmetry, while micro- and macrovascular parameters in the systemic circulation were assessed using pulse wave analysis.

Results

Six weeks of dapagliflozin treatment resulted in improvements in diabetes control, including blood glucose and insulin resistance, and reduced office and 24-h ambulatory blood pressure values. RCF decreased from 324 AU at baseline to 308 AU after treatment with dapagliflozin (p = 0.028), while there was little difference after the placebo (318 AU; p = 0.334). Furthermore, the arteriole remodelling that was seen after the placebo phase was not evident after the dapagliflozin phase. Central systolic and diastolic blood pressure values were significantly lower after 6 weeks of dapagliflozin, by 3.0 and 2.2 mmHg, respectively (p = 0.035 and 0.020, respectively vs. baseline).

Conclusions

Six weeks of dapagliflozin treatment resulted in numerous beneficial effects. In addition to achieving superior diabetes control and blood pressure, parameters associated with the early stages of vascular remodelling were also improved.

Trial registrationhttp://www.clinicaltrials.gov (NCT02383238)
Osteogenesis evaluation of duck’s feet-derived collagen/hydroxyapatite sponges immersed in dexamethasone
Authors: Kook Yeon Ji , Lee Dae Hoon , Song Jeong Eun , Tripathy Nirmalya , Jeon Yoo Shin , Jeon Ha Yan , Oliveira Joaquim M. , Reis Rui L. , Khang Gilson
Published: February 2017

Background

The aim of this study was to investigate the osteogenesis effects of DC and DC/HAp sponge immersed in without and with dexamethasone.

Methods

The experimental groups in this study were DC and DC/HAp sponge immersed in without dexamethasone (Dex(−)DC and Dex(−)-DC/HAp group) and with dexamethasone (Dex(+)-DC and Dex(+)-DC/HAp group). We characterized DC and DC/HAp sponge using compressive strength, scanning electron microscopy (SEM). Also, osteogenic differentiation of BMSCs on sponge (Dex(−)DC, Dex(−)-DC/HAp, Dex(+)-DC and Dex(+)-DC/HAp group) was assessed by SEM, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assay, alkaline phosphatase (ALP) activity assay and reverse transcription-PCR (RT-PCR).

Results

In this study, we assessed osteogenic differentiation of BMSCs on Duck’s feet-derived collagen (DC)/HAp sponge immersed with dexamethasone Dex(+)-DC/HAp. These results showed that Dex(+)-DC/HAp group increased cell proliferation and osteogenic differentiation of BMSCs during 28 days.

Conclusion

From these results, Dex(+)-DC/HAp can be envisioned as a potential biomaterial for bone regeneration applications.
Application of a complete workflow for 2D elastic full-waveform inversion to recorded shallow-seismic Rayleigh waves
Authors: Groos Lisa , Schäfer Martin , Forbriger Thomas , Bohlen Thomas
Published: February 2017

The S-wave velocity of the shallow subsurface can be inferred from shallow-seismic Rayleigh waves. Traditionally, the dispersion curves of the Rayleigh waves are inverted to obtain the (local) S-wave velocity as a function of depth. Two-dimensional elastic full-waveform inversion (FWI) has the potential to also infer lateral variations. We have developed a novel workflow for the application of 2D elastic FWI to recorded surface waves. During the preprocessing, we apply a line-source simulation (spreading correction) and perform an a priori estimation of the attenuation of waves. The iterative multiscale 2D elastic FWI workflow consists of the preconditioning of the gradients in the vicinity of the sources and a source-wavelet correction. The misfit is defined by the least-squares norm of normalized wavefields. We apply our workflow to a field data set that has been acquired on a predominantly depth-dependent velocity structure, and we compare the reconstructed S-wave velocity model with the result obtained by a 1D inversion based on wavefield spectra (Fourier-Bessel expansion coefficients). The 2D S-wave velocity model obtained by FWI shows an overall depth dependency that agrees well with the 1D inversion result. Both models can explain the main characteristics of the recorded seismograms. The small lateral variations in S-wave velocity introduced by FWI additionally explain the lateral changes of the recorded Rayleigh waves. The comparison thus verifies the applicability of our 2D FWI workflow and confirms the potential of FWI to reconstruct shallow small-scale lateral changes of S-wave velocity.
Feasibility study of combining metronidazole with chemotherapy.
Authors: Stewart D J , Maroun J A , Young V , Crook A F , Hopkins H S , Yan R C , Richard M T , Hugenholtz H , Bélanger R , Heringer R
Published: February 2017

Metronidazole, 1.5 g/sq m, was administered p.o. to patients with advanced malignancies 12 hr and 1 hr before and 6 hr and 24 hr after each of adriamycin, BCNU, and mitomycin-C. Doses of adriamycin varied from 50 to 90 mg/sq m. At an adriamycin dose of 75 mg/sq m, the median granulocyte nadir was 900/microliters and the median platelet nadir was 240,000/microliters. No enhancement of stomatitis or cardiotoxicity was noted at the doses studied. Doses of BCNU varied from 145 to 265 mg/sq m. At a BCNU dose of 240 mg/sq m, the median granulocyte nadir was 2600/microliters and the median platelet nadir was 102,000/microliters. Two patients developed hypotension that may have been due to a metronidazole-alcohol interaction. Doses of mitomycin-C varied from 10 to 20 mg/sq m. At a mitomycin-C dose of 20 mg/sq m, the median granulocyte nadir was 1300/microliters and the median platelet nadir was 81,000/microliters. Four of 40 patients developed pulmonary toxicity and one developed renal toxicity. Of 11 evaluable patients treated on the adriamycin regimen, 4 responded and 5 stabilized. With BCNU, 7 of 17 responded and 2 stabilized. With mitomycin-C, 2 of 32 responded and 12 stabilized. Overall, 4 of 8 patients with squamous cell carcinoma or adenocarcinoma of the lung attained partial remissions and one had a minor response. Using this metronidazole dose schedule, phase II studies are being conducted with adriamycin, 75 mg/sq m, in squamous cell and adenocarcinomas of the head and neck; with BCNU, 240 mg/sq m, in glioblastomas and squamous cell and adenocarcinoma of the lung; and with mitomycin-C, 20 mg/sq m, in adenocarcinomas of the breast and colon.
Phase I study of carboplatin given on a five-day intravenous schedule.
Authors: Rozencweig M , Nicaise C , Beer M , Crespeigne N , Van Rijmenant M , Lenaz L , Kenis Y
Published: February 2017

Twenty-six adult patients were entered in a phase I trial of carboplatin, a new cisplatin derivative with reduced potential for nephrotoxicity. All patients had solid tumors and the median World Health Organization performance score was 2 (0-3). Twelve patients had not received prior chemotherapy. The drug was administered as a 15-minute IV infusion, without pre- or posthydration, at daily doses of 40-125 mg/m2 for five consecutive days. Antiemetics were given only if needed. Thrombocytopenia and neutropenia were dose related and dose limiting. One patient died from septic shock at the highest dose level. Nonhemolytic anemia was also encountered. Nausea and vomiting were experienced by most patients but gastrointestinal intolerance was severe in only two patients. One patient had hypercreatininemia, which was minor and rapidly reversible. Other toxic effects consisted of negligible fatigue, paresthesia, pruritus, local pain, stomatitis, headache, and alopecia. Although none of the patients achieved a partial or complete response, antitumor effect was strongly suggested in two patients with thyroid and cervix cancer, respectively. Carboplatin is an attractive candidate for phase II trials. In good-risk patients, such trials could be initiated at a daily dose of 100 mg/m2 for five consecutive days every five to six weeks.
High-dose cytosine arabinoside in non-Hodgkin's lymphoma.
Authors: Kantarjian H , Barlogie B , Plunkett W , Velasquez W , McLaughlin P , Riggs S , Cabanillas F
Published: February 2017

Thirty-two patients with refractory non-Hodgkin's lymphoma were treated with high-dose cytosine arabinoside (ara-C) given at 2 g/m2 IV over three hours every 12 hours for 4-8 g/m2/course repeated at three to four week intervals. There were eight partial responses (29%) and two minor responses among 28 evaluable patients. The median response duration was 10 weeks (range, 6-33 weeks). The median survival was significantly prolonged in responders compared to nonresponders (28 versus 15 weeks; p = 0.03). Two additional patients treated with 12 g/m2/course died of sepsis and myelosuppression. The dose-limiting toxicity was myelosuppression, which was more pronounced in patients with prior extensive radiation therapy and bone marrow involvement. In vivo measurements of intracellular concentrations of ara-CTP, the active metabolite of ara-C, showed significantly higher values in bone marrows with lymphomatous involvement compared to normal bone marrows (210 versus 95 microM; p = 0.05), probably indicating a preferential formation and retention of ara-CTP in malignant cells compared to normal hemopoietic cells. In addition, higher ara-CTP levels were found in bone marrows that had higher percentages of cells in S phase.
A multifactorial analysis of prognostic factors in patients with liver metastases from colorectal carcinoma.
Authors: Lahr C J , Soong S J , Cloud G , Smith J W , Urist M M , Balch C M
Published: February 2017

A multifactorial analysis was used to identify the dominant prognostic variables predicting survival rates of 175 patients with hepatic metastases from colorectal carcinoma. Seven of 22 parameters examined simultaneously were found to independently influence the median survival rate in these patients: (1) elevated alkaline phosphatase (p = 0.0004), (2) elevated serum bilirubin level (p = 0.0005), (3) location of hepatic metastases (unilateral or bilateral, p = 0.0022), (4) number of metastatic nodes involved (0, 1-5, greater than 5; p = 0.0148), (5) depressed serum albumin (p = 0.0217), (6) whether or not the primary colorectal tumor was resected (p = 0.0013), and (7) chemotherapy (given or withheld, p = 0.0439). The prothrombin time, serum lactic dehydrogenase, and the number of hepatic metastases also correlated with survival, but they did not independently predict survival rates after other more dominant factors were accounted for. A mathematical equation for predicting an individual patient's clinical course once they developed hepatic metastases was derived from this statistical analysis. In addition, a simple and clinically useful guide for predicting outcome was developed that integrated the two most important risk factors, alkaline phosphatase and bilirubin.
Treatment of the carcinoid tumor and the malignant carcinoid syndrome.
Authors: Moertel C G
Published: February 2017

Certainly in treatment of the carcinoid tumor surgery has a well-established curative and palliative potential. The primary challenge is a knowledgable marriage between stage of disease and aggressiveness of operative procedure. Nonsurgical treatment of the malignant disease per se has thus far not produced optimum results and, in the opinion of this author, should still be confined to a clinical research setting. It would seem very doubtful, however, that the more mundane types of trials, empirically testing drug after drug and arbitrarily concocted drug combinations, is the most productive road to follow. There is an evident need for more sophisticated approaches to this tumor, which has unique metabolic characteristics that should be pharmacologically exploitable. Past experience has indicated that such a setting may permit dramatic therapeutic accomplishment. There is a strong need for animal models or established cell lines which would facilitate preclinical therapeutic exploration. The carcinoid syndrome presents an unparalleled opportunity for fundamental physiologic observations and for experimental therapeutic study that can have applicability not only in palliating the syndrome itself but also in the management of other pathophysiologic states that may involve more subtle abnormalities of the same hormonal mechanisms. The patient with the carcinoid tumor should not just be a fascinating curio for grand rounds exhibition. He should be a focal point for research involving an experienced, multidisciplinary clinical team supported by devoted basic scientists. If our patient resources and efforts can be concentrated in this manner, the carcinoid should be a strong candidate for the next medically curable human cancer.
Clinical pharmacokinetics of intraarterial cisplatin in humans.
Authors: Campbell T N , Howell S B , Pfeifle C E , Wung W E , Bookstein J
Published: February 2017

The pharmacokinetics of intraarterially administered cisplatin (DDP) were studied in three patients with large hepatic tumors, and one patient with a fibrous histiocytoma in the thigh, using an assay sensitive to only those forms of non-protein bound DDP capable of reacting with the nucleophilic ligand diethyldithiocarbamate. Each patient received continuous intravenous and intraarterial infusions at various dose rates, with and without concurrent infusion of the neutralizing agent sodium thiosulfate. Steady-state DDP concentrations were achieved within two hours, and the mean (+/- SEM) plasma clearance at infusion rates of 5-15 mg/m2 per hour was 345 +/- 45 mL/m2 per minute. Apparent plasma clearance did not vary significantly with route of infusion. Based on the plasma clearance, predicted values for the relative advantage of an intraarterial infusion (Rt) were less than two for hepatic infusion; observed values averaged 1.9 +/- 0.5 (+/- SEM). The infusion of thiosulfate did not significantly increase plasma clearance. The mean (+/- SEM) extraction ratio for hepatic infusions was 0.24 +/- 0.09, and for infusion of the peripheral soft tissue sarcoma it was 0.27 +/- 0.03. These data indicate that from the point of view of both the tumor and the systemic circulation there is only a limited pharmacologic advantage for intraarterial infusion of DDP into organs with plasma flows of greater than 350 mL/m2 per minute.
Phase I-II studies of oral tegafur (ftorafur).
Authors: Ansfield F J , Kallas G J , Singson J P
Published: February 2017

A total of 65 patients with advanced colorectal or breast cancer were given oral tegafur in the phase I study. Of these, 28 patients had accurately measurable lesions and were entered into the phase II study. Patients with liver metastasis, compromised bone marrow, or a decreased oral intake to less than 50% of their normal intake were given a poor-risk schedule consisting of 0.75 g/m2/day divided into 4 doses/day X 28 day unless early toxicity developed. In the absence of any of the above deficits, patients were given a good-risk schedule of 1.25 g/m2/day X 21 days if no toxicity appeared. The courses were followed by a 2-3-wk rest period depending upon the speed to recovery from all reactions and then repeated. Compared with 5-FU, nausea and vomiting occurred more frequently with tegafur while hematologic toxicity was less common and less severe. The paucity of significant hematologic toxicity permitted courses of this drug to be given safely on an outpatient basis even to the point of slight reaction for optimal dosing. No serious reactions occurred in any of the 65 patients. The clinical results showed partial regressions in 6 of 21 colorectal cancer patients and 3 of 7 breast cancer patients. Six of the 9 responses occurred in patients who had previous 5-FU trials. The average duration of regression in the colorectal cancer patients on oral tegafur was 9 mo with a significantly increased survival of the responders.
Phase I study of spirogermanium given daily.
Authors: Legha S S , Ajani J A , Bodey G P
Published: February 2017

Spirogermanium, an azaspirane compound, has recently had limited clinical trials using a schedule of intravenous injection one to three times every week. The observation of clinical antitumor activity and lack of myelosuppression prompted us to investigate further the clinical effects of spirogermanium administered on various schedules. A total of 52 patients with advanced metastatic tumors refractory to standard therapy were treated with spirogermanium. Three different schedules of drug administration were evaluated. Initially, a short daily IV infusion for 5 days every week was evaluated, starting with a dose of 30 mg/m2/day. A total of 22 patients received 69 courses with a dose range of 30-120 mg/m2/day for 5 days every week. The maximum tolerated dose was 100 mg/m2/day IV over 1 hr and 120 mg/m2 over 2-3 hr. In the second phase of the study, 12 patients received 41 courses of spirogermanium as a 24-hr continuous infusion for 5 days/wk at a dose of 150-375 mg/m2/day. The maximum tolerated dose was 200 mg/m2/day for 5 days. In the third phase of the study, 18 patients received spirogermanium as a continuous infusion daily for a median of 30 days (range 6-77 days) in a dose range of 100-200 mg/m2/day. The maximum tolerated dose was 150 mg/m2/day. Of the 44 assessable patients, 3 demonstrated a partial response and 3 had minor tumor regression; all responses occurred in lymphoma patients. The dose-limiting toxicity of spirogermanium was neurologic; other side effects consisted of mild anorexia, nausea and vomiting, and possible lung toxicity. There was no clear evidence of cumulative toxicity despite daily administration of spirogermanium. Our data suggest that spirogermanium can be administered daily by several different schedules, and the optimum dose depends on the infusion time and the duration of therapy. The delivery of drug by continuous infusion permitted administration of twofold higher dose levels compared to the standard IV schedules used in previous studies.
Breast cancer estrogen and progesterone receptor values: their distribution, degree of concordance, and relation to number of positive axillary nodes.
Authors: Fisher B , Wickerham D L , Brown A , Redmond C K
Published: February 2017

Increasing evidence indicates the importance of ascertaining the quantitative estrogen receptor (ER) and progesterone receptor (PR) content (in femtomoles per milligram cytosol protein) of primary breast cancers. Those values obtained from the tumors of 1,887 patients participating in National Surgical Adjuvant Breast and Bowel Project protocol B-09 have been analyzed to define (1) the distribution of tumor ER or PR according to patient age, (2) the distribution of tumor PR within a specific ER interval, and (3) the concordance of tumor ER and PR levels. The present findings indicate how predictive the knowledge of the amount of one receptor (e.g., ER) may be for estimating the amount of the other (PR), when the latter is unknown.
Local or regionally recurrent carcinoma of the breast: results of therapy in 121 patients.
Authors: Beck T M , Hart N E , Woodard D A , Smith C E
Published: February 2017

Local or regional recurrence after primary surgical management for carcinoma of the breast was retrospectively evaluated by presenting stage and management in 121 patients. None had evidence of systemic disease. Management consisted of surgical removal only in 11 patients, removal followed by irradiation in 25, biopsy only followed by irradiation in 43, hormonal therapy after biopsy in 30, and chemotherapy after biopsy in 12. Mean and median follow-up for all patients was 46.9 and 31.5 months, respectively. Patients experiencing a recurrence within 24 months of primary surgical management experienced the worst overall and disease-free survival. The group of 42 patients with residual disease who received systemic therapy after biopsy had improved disease-free and overall survival at 5 years in comparison to the group of 43 patients who received local therapy after biopsy (p less than or equal to 0.05). Radiation therapy produced more frequent and durable control of local disease than did systemic therapy. Patients who had a complete response to applied therapy had significant improvement in overall survival.
Painful gynecomastia following cytotoxic therapy for testis cancer: a potentially favorable prognostic sign?
Authors: Trump D L , Anderson S A
Published: February 2017

Ninety-six patients who received cytotoxic chemotherapy for germ cell neoplasms of the testis were studied. Painful gynecomastia developed in eight patients (8%) between 6 and 24 weeks after the initiation of cytotoxic therapy (mean 18 wk). Serum content of the beta subunit of human chorionic gonadotropin was normal in each patient when gynecomastia developed. Gynecomastia occurred following cytotoxic therapy for advanced disease in seven patients, and one patient was receiving adjunctive drug therapy for stage I disease. Six of the seven patients with advanced disease were in complete remission when gynecomastia developed; survival was superior in patients who developed treatment-related gynecomastia compared to those patients who did not (p less than 0.05). Gynecomastia may occur in adult males after cytotoxic therapy for testis cancer; such gynecomastia does not necessarily indicate recurrent malignancy and may be a favorable prognostic sign.
Extraskeletal Ewing's sarcoma: results of combined modality treatment.
Authors: Kinsella T J , Triche T J , Dickman P S , Costa J , Tepper J E , Glaubiger D
Published: February 2017

Eleven patients with extraskeletal Ewing's sarcoma (EES) were treated with combined modality therapy at the National Cancer Institute. The diagnosis of EES was reserved for lesions that were identical to Ewing's sarcoma of bone by light and electron microscopy. Diagnostic work-up to rule out a skeletal primary included bone scan, localized views of adjacent bone, and bone tomography. Seven patients presented with an extremity primary and four patients had a truncal primary. No patients had evidence of metastases at presentation. Patients were treated with combined modality therapy consisting of high-dose local irradiation and vincristine, actinomycin D, and cyclophosphamide chemotherapy following a biopsy or local excision. No attempt was made to excise widely the primary tumor mass. Gross tumors generally responded rapidly to the combined modality treatment. Of 11 patients, seven (64%) remain disease free, with a follow-up of three to seven years from completion of therapy. Long-term local control was established in nine of 11 patients (82%). Autopsy findings on two patients with local failure showed no tumor involvement of adjacent bone. Attempts at gross resections by radical surgical procedures do not routinely appear to be necessary in light of the high local control rates with high-dose irradiation.
A technique to quantify cytoreduction in the bone marrow induced by cytotoxic chemotherapy.
Authors: Blumenreich M S , Strife A , Clarkson B D
Published: February 2017

A technique to quantify the cytoreduction in the bone marrow induced by chemotherapy in leukemia patients is reported. Bone-marrow core biopsies are obtained and the specimens are carefully minced in McCoy's 5a medium with a 20% fetal bovine serum supplement. The number of cells present per millimeter length of bone-marrow specimen is obtained by finding the concentration of cells in the supernatant, multiplying by the total volume of the supernatant, and dividing by the length of the bone-marrow biopsy specimen. Cytocentrifuge preparations are made from this supernatant and stained by standard techniques. Once the percentage of blasts is found, the absolute number of blasts per millimeter of bone marrow can be calculated. Serial measurements were made in 19 patients: nine patients were receiving first-line therapy for acute nonlymphocytic leukemia, and 10 were given experimental chemotherapy, which consisted of prolonged infusions of thymidine and cytosine arabinoside in six, and short infusions of thymidine, cystosine arabinoside, and phosphonoacetyl-l-aspartate, daily for five days in four. No patient with less than 2 log10 reduction in the number of marrow blasts achieved a remission, while only one patient in whom there was more than a 2 log10 reduction in the number of blasts failed to do so.
Human tumor clonogenic assay in patients with unknown primary carcinomas.
Authors: Greenberg B R , Salmon S E
Published: February 2017

The Human Tumor Clonogenic Assay (HTCA) was used in patients with unknown primary carcinomas (UPC) to evaluate chemosensitivity in vitro for this patient group and to possibly aid in the selection of chemotherapy for clinical trial. A total of 178 drug assays including 15 standard and 13 experimental anti-cancer drugs were performed on tumor cells from 19 patients. A median of six drugs were studied in vitro per patient. Sensitivity was noted in only 3.4% of the studies (six drug assays). The marked in vitro pattern of resistance observed with UPC correlates well with the known clinical experience with this entity. Ten patients were evaluable for clinical correlation of response between in vitro and in vivo sensitivity; however, many received drug combinations and not all the drugs had been tested in vitro. One of six evaluable patients exhibiting in vitro sensitivity and one of four with in vitro resistance achieved remission. Additional single-agent in vitro/in vivo correlations will be needed to establish whether HTCA will have any future impact in the treatment of patients with UPC. A more promising application of HTCA for UPC would appear to be as an aid in screening and discovery of new drugs of potentially greater efficacy for this resistant tumor category.
Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer.
Authors: Clark G M , Osborne C K , McGuire W L
Published: February 2017

The relationships between estrogen receptor, progesterone receptor, and a variety of patient characteristics are described for 2,977 women with primary breast cancer. Older women were more likely to be estrogen-receptor positive than younger women. When patient age and menopausal status were analyzed together, age was found to be the primary determinant of increased estrogen-receptor concentrations. There appeared to be no relationship with progesterone receptor for either age or menopausal status when these variables were analyzed separately. But premenopausal women had higher progesterone receptor concentrations than postmenopausal women when patients of the same age were compared, perhaps reflecting greater estrogen-mediated synthesis of progesterone receptor. Tumor size was negatively related to steroid receptor concentrations, but no relationships were observed between steroid receptors and either the number of positive axillary lymph nodes or the location of the primary tumor.