Intensity-modulated radiotherapy increases dose to the brachial plexus compared with conventional radiotherapy for head and neck cancer.

OBJECTIVE: The preferential use of intensity-modulated radiotherapy (IMRT) over conventional radiotherapy (CRT) in the treatment of head and neck cancer has raised concerns regarding dose to non-target tissue. The purpose of this study was to compare dose-volume characteristics with the brachial plexus between treatment plans generated by IMRT and CRT using several common treatment scenarios. METHOD: The brachial plexus was delineated on radiation treatment planning CT scans from 10 patients undergoing IMRT for locally advanced head and neck cancer using a Radiation Therapy Oncology Group-endorsed atlas. No brachial plexus constraint was used. For each patient, a conventional three-field shrinking-field plan was generated and the dose-volume histogram (DVH) for the brachial plexus was compared with that of the IMRT plan. RESULTS: The mean irradiated volumes of the brachial plexus using the IMRT vs the CRT plan, respectively, were as follows: V50 (18±5 ml) vs (11±6 ml), p = 0.01; V60 (6±4 ml) vs (3±3 ml), p = 0.02; V66 (3±1 ml) vs (1±1 ml), p = 0.04, V70 (0±1 ml) vs (0±1 ml), p = 0.68. The maximum point dose to the brachial plexus was 68.9 Gy (range 62.3-78.7 Gy) and 66.1 Gy (range 60.2-75.6 Gy) for the IMRT and CRT plans, respectively (p = 0.01). CONCLUSION: Dose to the brachial plexus is significantly increased among patients undergoing IMRT compared with CRT for head and neck cancer. Preliminary studies on brachial plexus-sparing IMRT are in progress.

Primary clear cell adenocarcinoma of the rectovaginal septum treated with concurrent chemoradiation therapy: a case report.

Primary clear cell adenocarcinoma of the rectovaginal septum is rare and typically emerges in the setting of endometriosis. We report a case of a 52-year-old woman with clear cell adenocarcinoma of the rectovaginal septum presenting with vaginal hemorrhage. Management with concurrent chemoradiation with cisplatin and paclitaxel is discussed. Six years following the completion of treatment, the patient is without evidence of disease or significant long-term toxicity.

The impact of age and comorbidity on survival outcomes and treatment patterns in prostate cancer.

The management of localized prostate cancer is based on stage, grade, PSA, and subjective assessment of comorbidity and life expectancy. Over the last 15 y, stage migration and the improved use of Gleason sum, PSA and TNM staging have led to many treatment options for patients with newly diagnosed localized prostate cancer. At the same time, advances in treatment techniques have helped decrease the long-term complications of surgery and radiotherapy. However, the importance of age and comorbidity, in survival outcomes and treatment decision-making has been largely overlooked. Currently, stage, grade, and PSA are the only quantifiable variables consistently used in research and treatment decision-making. Comorbidity and life expectancy have remained largely subjective variables. Increasing longevity and a rapidly aging population have made age and comorbidity increasingly important factors in clinical research and treatment decision-making. This article reviews the importance of age and comorbidity on treatment decisions and survival outcomes in prostate cancer, as well as their use as objectively quantifiable variables. Examples from the general oncology literature are given. The overview also examines validated comorbidity indices and advocates the use of the Charlson Comorbidity Index (CCI) in research outcomes and treatment decision-making in prostate cancer. Several clinical vignettes are provided to demonstrate the potential clinical utility of the CCI as applied to prostate cancer.

Prophylactic hemodialysis in the treatment of acute renal failure. Annals of Internal Medicine, 53:992-1016, 1960.

Prophylactic hemodialysis has been employed in the treatment of 15 patients with acute renal failure due to acute tubular necrosis (12), bilateral renal cortical necrosis (two), and poststreptococcal glomerulonephritis (one). Dialyses, usually lasting six hours each, were begun before clinical evidence of uremia developed in each patient and/or before the nonprotein nitrogen reached 200 mg.%, and were repeated daily or often enough to maintain the nonprotein nitrogen below 150 mg.%. The hypothesis underlying this technic postulates (1) that wasting, sepsis and impaired wound healing in these patients may reflect tissue injury by the same dialyzable toxic agents which produce the uremic symptoms that are readily reversible by dialysis, and (2) that repeated dialyses should therefore prevent both clinical uremia and the later, often lethal sequelae. The results contrast dramatically with our own past experience in treating patients with acute renal failure with a carefully executed medical regimen together with hemodialysis on conventional indications. Except in one instance of crush injury with progressive intracerebral damage, and one brief occasion in another individual, these patients experienced a stable, convalescent clinical course, remained free of uremic symptoms or chemical imbalances, ate at least three meals daily which were unrestricted in amount and composition, and were ambulatory between dialyses unless confined to bed by associated disease. Wounds healed well. Infection either did not occur, or subsided after appropriate therapy. Fluid restriction was liberalized by means of ultrafiltration with dialysis. Regional heparinization of only the extracorporeal circuit eliminated actual or impending bleeding as a contraindication to dialysis. Chronic vessel cannulation made the frequent dialyses possible, but may have provided the route for repeated, transient bacterial contamination of the blood stream in the first hour of many dialyses. Marked anemia, despite reticulocytosis, moderate to mild weight loss and some mental deficit persisted in spite of the general clinical improvement and well-being. Three patients with tubular necrosis died after seven, 11 and 26 days of oliguria; both patients with bilateral renal cortical necrosis also succumbed, on the seventy-third and ninety-second days of renal failure, and after 29 and 40 dialyses, respectively. At autopsy, evidence of sepsis was conspicuously absent. The remaining 10 patients survived. Thus some, but not all, clinical manifestations of acute renal failure appear to be favorably influenced by prophylactic dialysis treatment. Our initial experience in this group of 15 patients does not of course prove that freedom from complications and a significantly better outlook for survival can be assured to patients with acute renal failure by these methods. However, it seems to offer a reasonable hope of this possibility which we cannot attach to management by medical measures alone, or by dialysis on conventional indications. If this hope is realized in greatly extended, subsequent series, then it seems inevitable that some form of prophylactic dialysis, or some equally effective alternative, should be adopted in treating the majority of patients with acute renal failure.

Human T-cell lymphotropic virus type II-associated myelopathy: clinical and immunologic profiles.

Human T-cell lymphotropic virus type II (HTLV-II) is endemic in several ethnic tribes and among intravenous drug users in metropolitan areas. Despite the presence of HTLV-II in these various populations, the association of HTLV-II with disease is sparse and mainly limited to isolated case reports. This study is an extension of an earlier description of an HTLV-II-infected patient with neurologic disease and presents the clinical and immunologic findings of 4 patients with HTLV-II seropositivity and spastic paraparesis. The patients are of African-American origin with 3 of the patients being of Amerindian descent. All of the patients are seronegative for the human immunodeficiency virus (HIV). The patients progressed to a nonambulatory state in less than 5 years. Magnetic resonance imaging studies obtained from 3 of the patients demonstrated white matter disease in the cerebrum and spinal cord. The cerebrospinal fluid and serum contained antibodies to HTLV-II. The presence of proviral HTLV-II was confirmed by polymerase chain reaction analysis of peripheral blood lymphocytes (PBLs). A spinal cord biopsy from 1 patient demonstrated HTLV RNA within a lesion. Immunologic studies on 2 patients demonstrated that spontaneous lymphoproliferation of PBLs was present but decreased relative to HTLV-I-infected patients. The clinical and immunologic findings from these HTLV-II-infected patient resemble those found in HTLV-I-associated myelopathy/tropical spastic paraparesis.

Modern chemotherapy for brucellosis in humans.

The most effective, least toxic chemotherapy for human brucellosis is still undecided. In vitro, the antibiotics most active against Brucella include the tetracyclines, the aminoglycosides, the aminopenicillins, some cephalosporins, trimethoprim-sulfamethoxazole, erythromycin, rifampin, and some new fluorinated quinolones. Because Brucella species are facultative intracellular parasites, the penetration of drugs into and within phagocytes and phagosomes can be problematic and can best be studied in experimental animals or tissue cultures. In humans, the effectiveness of various regimens of chemotherapy has been compared best in acute bacteremic infections by assessment of the control of symptoms, bacteremia, complications, and relapses. The standard therapy against which all other therapies have been judged is a combination of tetracycline and streptomycin, which is almost universally effective but fails to prevent relapse in 10% of cases. A combination of oral doxycycline and rifampin is convenient and currently popular; it is highly effective, with an average relapse rate of only 8.4%. Trimethoprim-sulfamethoxazole is less effective in controlling bacteremia and other manifestations: in collected series, 5.7% of cases did not respond and 12% relapsed. Drug-resistant Brucella strains are rarely a cause of therapy failure. Localized brucellosis poses special problems, often requiring surgery in addition to prolonged combined chemotherapy.

Bovine superfetation by natural conception secondary to an embryo transfer pregnancy.

There was only one embryo transferred to the recipient female. There was no chance for natural service to occur from 21 days prior to the transfer of the embryo to 31 days after the transfer of the 7 day old blastocyst. The surrogate female was palpated as being 38 days pregnant 31 days after the transfer of a 7 day old embryo by an experienced professional before being exposed to the natural service sire. The second fetus was of a different sex than the first and was approximately 60 days less mature. All other pregnancies within this well managed herd were accounted for and no other cows calved within the area close to that time. The remaining recipients carried pregnancies to the approximate expected calving date. Conclusion. This case report should support earlier evidence that superfetation in the bovine can and does occur.

Influence of inoculum size on comparative susceptibilities of penicillinase-positive and -negative Neisseria gonorrhoeae to 31 antimicrobial agents.

The effects of two inoculum sizes (10(4) and 10(6) CFU) on the MICs of 20 beta-lactam antibiotics, 4 aminoglycosides, and 7 other antimicrobial agents were compared for 102 unselected strains of Neisseria gonorrhoeae (26 penicillinase positive and 76 penicillinase negative), with three replicates for each test. The method was agar plate dilution on Mueller-Hinton agar supplemented with 1% hemoglobin and 1% IsoVitaleX. For penicillinase-positive strains, a large inoculum (10(6) CFU) increased the MIC greater than or equal to 16-fold for benzylpenicillin, piperacillin, azlocillin, and mezlocillin and increased the MIC greater than or equal to 8-fold for ampicillin, cefoperazone, ceftazidime, cefonicid, and cefamandole. The inoculum size had little or no influence on MICs of any antimicrobial agent for penicillinase-negative strains. For penicillinase-positive strains, the most active antibiotics (MIC, less than or equal to 0.001 microgram/ml) were the new cephalosporins: cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, and cefmenoxime. For penicillinase-negative strains, the most active antibiotics were piperacillin, ceftriaxone, ceftizoxime, and cefmenoxime (MIC, less than or equal to 0.001 microgram/ml), closely followed by ceftazidime, moxalactam, azlocillin, mezlocillin, and cefuroxime.

Primary abdominal pregnancy in the spleen: a case report.

The spleen was the source of hemorrhage in a 27-yr-old woman, known to be 6 wk pregnant when she presented in acute shock for intra-abdominal bleeding requiring immediate resuscitation and emergency laparotomy. Microscopic examination of the splenectomy specimen demonstrated a primary pregnancy implanted within the subcapsular splenic parenchyma.

Correlation of moxalactam (LY127935) susceptibility tests by disk diffusion and agar plate dilution methods.

Susceptibility of pathogenic aerobic bacteria to moxalactam (LY127935) was compared by two methods, diffusion from 30-microgram disks and agar plate dilution. The two methods gave a satisfactory degree of correlation when compared by linear regression, but the slope of the linear regression was significantly steeper for gram-negative bacilli (Enterobacteriaceae and Pseudomonas aeruginosa) than for coccal organisms (streptococci and staphylococci). The largest zone diameters by disk diffusion were found with Citrobacter, Proteus, Escherichia coli, Klebsiella, and Enterobacter strains. The error rate-bounded method of Metzler and DeHaan (J. Infect. Dis. 130:588-594, 1974) gave useful breakpoints of disk zone sizes for moxalactam resistance and susceptibility.

Determination of tolerance to antibiotic bactericidal activity on Kirby-Bauer susceptibility plates.

A rapid method utilizing Kirby-Bauer susceptibility plates was developed to determine bacterial tolerance to antibiotic bactericidal activity. After completion of initial antibiotic disk susceptibility testing, the disks containing cephalothin, cefazolin, nafcillin, oxacillin, and methicillin were removed and replaced with disks containing a potent beta-lactamase. The plates were reincubated for 18-24 hours and examined for regrowth of organisms within the original zone of inhibition. For 15 of 16 patients who had serious Staphylococcus aureus infections, the method correlated with clinical outcome of antibiotic chemotherapy. Broth dilution tests for bactericidal activity only correlated with clinical response for 11 of 16 patients. One hundred consecutive clinical S. aureus isolates tested with the new method demonstrated tolerance in 27% of strains to cephalothin, 15% to cefazolin, 1% to oxacillin, and 2% of nafcillin.

Failure of single doses of cefazolin and cefamandole to penetrate experimental chronic Escherichia coli abdominal abscesses.

Four perforated capsules were implanted into the abdominal cavity of each of three rabbits. After 4 to 5 weeks, single doses of cefazolin (30 mg/kg) or cefamandole (90 mg/kg) were administered intramuscularly. Peak levels of the respective drugs in serum were 104 +/- 10 and 127 +/- 5 micrograms/ml (mean +/- standard error); corresponding peak levels in capsule fluid were 6.3 +/- 2.3 micrograms/ml. Sixteen weeks after implantation, 2 X 10(6) colony-forming units of a strain of Escherichia coli susceptible to cefazolin (minimum inhibitory concentration, 1.0 microgram/ml) and cefamandole (minimum inhibitory concentration, less than 0.125 microgram/ml) was introduced into each of the 12 capsules. Chronic infection was established in seven of the capsules. At 4 to 6 weeks after infection, cefazolin and cefamandole were again administered. Peak serum concentrations were 102 +/- 3.3 micrograms/ml for cefazolin and 148 +/- 6.7 micrograms/ml for cefamandole. Peak concentrations in noninfected capsules were 7.5 +/- 3.4 and 12.1 +/- 2.1 micrograms/ml, respectively, not statistically different from the first study (P greater than 0.2). However, peak concentrations in infected capsules (less than 0.3 microgram/ml) were strikingly lower than in uninfected capsules (P less than 0.002). In keeping with the latter finding, quantitative cultures of E. coli in the infected capsules remained unchanged. Administration of [14C]cefamandole indicated that low drug levels were a result of poor drug penetration rather than drug inactivation or binding. Lack of vascularity and capsule wall necrosis may be responsible for poor drug penetration.

Comparative activities of the oxa-beta-lactam LY127935, cefotaxime, cefoperazone, cefamandole, and ticarcillin against multiply resistant gram-negative bacilli.

A total of 91 multiply resistant bacterial strains, including Klebsiella pneumoniae (32 strains), Pseudomonas aeruginosa (16 strains), and Serratia marcescens (43 strains), were collected during hospital epidemics of nosocomial infection from 1975 to 1979. These strains were resistant to gentamicin, tobramycin, cephalothin, chloramphenicol, and ampicillin. Their susceptibility to three new broad-spectrum beta-lactams, LY127935 (a 1-oxa-beta-lactam), cefotaxime (HR 756), and cefoperazone (T 1551), was compared with the susceptibility of random strains of nine species of aerobic gram-negative bacilli collected in the same hospital in 1979. Susceptibility to cefamandole and ticarcillin was also determined. Strains of staphylococci and streptococci from that hospital and two nearby city-county hospitals were also compared for the three new cephalosporins and other effective antibiotics. The agar dilution method was used to measure the minimum inhibitory concentration for each antibiotic. The multiply resistant strains (minimum inhibitory concentration for gentamicin >/= 8 mug/ml) usually were as susceptible to the three new broad-spectrum beta-lactams as were non-multiply resistant strains. Both Klebsiella pneumoniae and Serratia marcescens, including multiply resistant and non-multiply resistant strains, were most susceptible to the 1-oxa-beta-lactam LY127935 and cefotaxime. P. aeruginosa (both multiply resistant and non-multiply resistant strains) were most susceptible to cefoperazone. All three new beta-lactams were active against non-multiply resistant strains of Escherichia coli, Enterobacter spp., Proteus spp., and Citrobacter spp. Providencia stuartii were most susceptible to cefotaxime and the 1-oxa-beta-lactam LY127935. The three new beta-lactams were all less active against staphylococci (especially methicillin-resistant Staphylococcus aureus) than cephalothin. Streptococcus pyogenes and S. pneumoniae were very susceptible to cefotaxime and cefoperazone, though less susceptible to LY127935. None of the three new beta-lactams was active against S. faecalis. All were very active against both penicillinase-positive and -negative strains of Neisseria gonorrhoeae.

Evaluation of a commercial microdilution system for quantitative susceptibility testing of aminoglycosides against multidrug-resistant, gram-negative bacilli.

Susceptibility of clinical isolates of Pseudomonas aeruginosa (29 isolates), Klebsiella species (54 isolates), Escherichia coli (28 isolates), Serratia marcescens (28 isolates), and Enterobacter species (29 isolates) to gentamicin, tobramycin, and amikacin was determined by the following three methods: commercial broth microdilution trays, standard agar dilution, and disk diffusion susceptibility. A total of 504 tests were performed by each method, and overall susceptibility or resistance determined by the broth microdilution method agreed with that determined by the agar dilution method in 92.7% of the tests, whereas results from the disk diffusion method agreed with those from the agar dilution method in 91.9% of the tests. The broth microdilution and disk diffusion methods agreed with each other 88.7% of the time. The broth microdilution system results varied from the agar dilution method results by more than one dilution in 121 of 504 determinations (24%); however, this altered susceptibility determinations in only 7.3% of the assays. E. coli isolates were found to be quantitatively more resistant to the aminoglycosides with the broth microdilution method than with the agar dilution method. In contrast, the broth microdilution method demonstrated P. aeruginosa to be quantitatively more susceptible to the aminoglycosides than when the results were obtained by the agar dilution method. The Micro-Media Systems method is economical, reliable, rapid, and simple to perform and yields quantitative minimum inhibitory concentrations.

Treatment of Pseudomonas endophthalmitis associated with prosthetic intraocular lens implantation.

Eight patients were treated for Pseudomonas endophthalmitis associated with the implantation of contaminated intraocular lenses. All patients showed clinical signs of infection (loss of red reflex, diminished visual acuity, and intraocular lens coagulum) and P. aeruginosa was isolated from vitreous aspirates and unused lenses of the same lot. Antibiotic treatment was initiated with systemic penicillin G, cephalothin, and chloramphenicol as well as subtenon-injected gentamicin. After identification of the organism, treatment was continued with systemic carbenicillin and gentamicin and subtenon-injected gentamicin. The intraocular lens was left in place for the first 48 hours of treatment in all eight patients. Five patients were successfully treated without removal of the intraocular lens and attained visual acuity of 6/6 (20/20) to 6/15 (20/50). Three patients (the two most seriously infected and one in whom antibiotics were discontinued) eventually lost their infected eye. Vitreous concentrations of gentamicin were good in one patient (1.7 micrograms/ml) and undetectable in another. Carbenicillin concentrations in vitreous (96 and 140 micrograms/ml) were high in two patients sampled. Endophthalmitis in the presence of a prosthetic intraocular lens can be successfully treated in some patients without removal of the prosthesis.