Evaluation of backscatter dose from internal lead shielding in clinical electron beams using EGSnrc Monte Carlo simulations.

Internal lead shielding is utilized during superficial electron beam treatments of the head and neck, such as lip carcinoma. Methods for predicting backscattered dose include the use of empirical equations or performing physical measurements. The accuracy of these empirical equations required verification for the local electron beams. In this study, a Monte Carlo model of a Siemens Artiste linac was developed for 6, 9, 12, and 15 MeV electron beams using the EGSnrc MC package. The model was verified against physical measurements to an accuracy of better than 2% and 2mm. Multiple MC simulations of lead interfaces at different depths, corresponding to mean electron energies in the range of 0.2-14 MeV at the interfaces, were performed to calculate electron backscatter values. The simulated electron backscatter was compared with current empirical equations to ascertain their accuracy. The major finding was that the current set of backscatter equations does not accurately predict electron backscatter, particularly in the lower energies region. A new equation was derived which enables estimation of electron backscatter factor at any depth upstream from the interface for the local treatment machines. The derived equation agreed to within 1.5% of the MC simulated electron backscatter at the lead interface and upstream positions. Verification of the equation was performed by comparing to measurements of the electron backscatter factor using Gafchromic EBT2 film. These results show a mean value of 0.997 ± 0.022 to 1σ of the predicted values of electron backscatter. The new empirical equation presented can accurately estimate electron backscatter factor from lead shielding in the range of 0.2 to 14 MeV for the local linacs.

Gastric wall erosion by an amebic liver abscess in a 3-year-old girl.

The occurrence of an amebic liver abscess (ALA) rupturing into the stomach is reported. ALAs in children can have atypical presentations, resulting in delayed diagnosis and increased morbidity and mortality. Timely treatment is usually followed by complete recovery.

Candida isolates from neonates: frequency of misidentification and reduced fluconazole susceptibility.

Systemic candidiasis affects 1.6 to 4.5% of very low birth weight (8 microg/ml.

Management of neonatal candidiasis. Neonatal Candidiasis Study Group.

OBJECTIVE: To identify areas of consensus and controversy in the management of neonatal candidiasis. METHODS: A questionnaire was distributed to US-based members of the Pediatric Infectious Diseases Society and a sampling of US neonatologists. RESULTS: Three hundred eighty evaluable questionnaires were returned (42% of those mailed). Ninety-five percent of respondents have cared for an infant with systemic candidiasis in the past 2 years. Fluconazole and liposomal amphotericin are used to some extent by 90 and 69% of respondents, respectively. A single blood culture positive for Candida led to a recommendation for immediate treatment by 99%; amphotericin B was the preferred therapy for candidemia (88%). More than 80% of respondents would request cerebrospinal fluid, urine and repeat blood cultures and ophthalmologic examination in the evaluation of candidemia. If a cerebrospinal fluid culture is positive, 25% would use amphotericin B alone whereas 62% would add flucytosine. For candiduria Society members chose fluconazole therapy more often than did neonatologists, 23% vs. 3.4% (P<0.001). There was no consensus concerning duration of therapy, use of an amphotericin B test dose or management of a central catheter in place during candidemia. CONCLUSIONS: Systemic candidiasis in neonates is a frequently encountered clinical problem. There is agreement that prompt therapy with amphotericin B is required if a blood culture is positive for Candida and that such infants require additional evaluations. Other antifungals (fluconazole, liposomal amphotericin B) are used to some extent in this population. Many issues in management have no clear consensus and warrant further research.

Chemotactic factors stimulate CD18-dependent canine neutrophil adherence and motility on lung fibroblasts.

The mechanisms by which neutrophils migrate through the alveolar interstitium during acute lung inflammation are unknown. We wished to determine whether platelet-activating factor (PAF) and IL-8, two important mediators in neutrophil transendothelial migration, stimulated neutrophil adherence and motility on lung fibroblasts. Canine fibroblasts grown from lung explants were characterized by light and electron microscopy, and flow cytometry. Unstimulated neutrophils adhered poorly (less than 2%) to cultured fibroblasts. However, neutrophils stimulated with PAF (20-200 nM) showed a dose-dependent increase in adherence that was largely (70%) mediated by the beta 2 (CD11/CD18) integrins; adherence was less dependent (50%) on fibroblast intercellular adhesion molecule-1. Conversely, neutrophils stimulated with canine rIL-8 did not increase their adherence to fibroblasts. PAF-stimulated neutrophils were nonmotile on the surface of the fibroblast, but subsequent addition of rIL-8 (10(-8) M) induced motility that was entirely CD1 8 dependent. Fibroblasts stimulated with human rTNF-alpha or Escherichia coli endotoxin (LPS) were a significant source of IL-8 mRNA. In response to rTNF-alpha (50 U/ml), IL-8 mRNA was detected at 2 h by northern blot analysis; it peaked at 6 h and returned to baseline by 24 h. Fibroblasts stimulated with rTNF-alpha secreted IL-8 protein into the culture medium; secreted IL-8 was chemotactic for neutrophils. These data suggest that fibroblasts can function not only as an adhesive substrate, but also as a source of stimulation for neutrophil migration through the inflamed alveolar interstitium.

Group B streptococci elicit leukotriene B4 and interleukin-8 from human monocytes: neonates exhibit a diminished response.

Neonatal monocytes have diminished function compared with adult cells. The ability to recruit neutrophils through elaboration of chemoattractants has not been evaluated in humans. The pattern of chemoattractant release induced by group B streptococci (GBS) also is unknown. Adult and cord blood monocytes were stimulated with GBS. Supernatants were used as the attractant in blind well chambers; migration to neonatal supernatants was diminished. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) were released in greater quantities by adult monocytes in response to either GBS or lipopolysaccharide. Opsonization of GBS was not required for IL-8 release. Adult monocytes released more LTB4 when stimulated with unopsonized GBS than with opsonized GBS; the neonate's LTB4 production did not increase. IL-8 and LTB4 accounted for the majority of chemoattractant activity released in response to GBS. Decreased production of LTB4 and IL-8 may contribute to the neonate's poor host response to GBS.

Invasive fungal dermatitis in the < or = 1000-gram neonate.

OBJECTIVE: In 1991, we noted the emergence amongst our extremely low birth weight neonates of a new clinical entity, invasive fungal dermatitis, characterized by erosive, crusting lesions and a high rate of subsequent systemic fungal infection. We sought to define this condition and examine potential risk factors. METHODS: Sixteen neonates with invasive fungal dermatitis were seen during a 2-year period in three Baylor College of Medicine affiliated intensive care nurseries. Seven were confirmed cases, with skin biopsy evidence of invasion beyond the stratum corneum. Nine had a consistent clinical course and a positive potassium hydroxide examination of skin scrapings or isolation of fungi from skin or systemic cultures. Three controls were matched to each case by hospital, date of admission, and birth weight. Data was collected by retrospective chart review. RESULTS: Invasive fungal dermatitis occurred in 5.9% of at-risk infants. Case patients had a mean birth weight of 635 g and developed skin lesions at a mean age of 9 days (range, 6 to 14). Candida albicans was the most commonly implicated pathogen, but other Candida species, Aspergillus, Trichosporon beigelii, and Curvularia were also seen. Disseminated infection occurred in 69%, all due to Candida sp. Case patients were significantly more premature than controls (mean gestation, 24.4 vs 25.9 weeks) and were more likely to be delivered vaginally (81% vs 50%). Postnatal steroids were administered to cases (81%) more often than controls (46%). Case patients had more prolonged hyperglycemia (as assessed by insulin administration) than controls (mean 4.3 vs 2.0 days). CONCLUSIONS: Invasive fungal dermatitis is a disease of the smallest, most immature neonates and is associated with vaginal birth, steroid administration, and hyperglycemia. We speculate that the skin serves as a portal of entry for colonizing fungal species and may thus lead to disseminated infection. Methods to improve skin barrier function may be useful in preventing this disorder.

Endotracheal colonization with Candida enhances risk of systemic candidiasis in very low birth weight neonates.

OBJECTIVE: To determine whether growth of Candida from an endotracheal aspirate identifies a population of very low birth weight (VLBW; < or = 1500 gm) neonates at increased risk of systemic candidiasis. DESIGN: Prospective evaluation with weekly cultures of endotracheal and rectal specimens to determine colonization status. SUBJECTS: One hundred sixteen VLBW neonates (mean birth weight, 975 +/- 23 gm, estimated gestational age, 27.6 +/- 0.2 weeks) with endotracheal tubes in place who were admitted to a level III nursery between Jan. 8 and Dec. 2, 1992. RESULTS: Of the 116 subjects, 39 infants were colonized with Candida (34%). Thirteen neonates had growth of Candida in one or more cultures of endotracheal specimens. Eleven of these could be examined, and in five systemic disease developed (disease in 5/11 vs 2/26; relative risk = 5.9; 95% confidence interval, 1.34 to 26). Eight infants were colonized with Candida in the first week of life. Seven of these could be examined, and in five systemic candidiasis developed (disease in 5/7 vs 2/30; RR = 9.3; 95% confidence interval, 2.3 to 38.0). CONCLUSIONS: Colonization with Candida occurs frequently in VLBW infants. Progression from colonization to systemic infection is more common in the smallest neonates. Detection of colonization in the first week of life or the growth of Candida from an endotracheal aspirate identifies a group of VLBW neonates with an endotracheal tube in place whose risk of systemic candidiasis is increased. A prospective trial of intervention in this high-risk population is warranted.

Combination chemotherapy with teniposide (VM26) and carboplatin in small cell lung cancer.

Seventy patients with previously untreated histologically proven small cell lung cancer (SCLC) were treated with a combination of teniposide 60 mg/m2 intravenously (i.v.) on days 1 through 5 and carboplatin 400 mg/m2 i.v. on day 1 every 28 days for six courses. Patients with limited stage disease, (LD) who achieved a response, subsequently received 2,000 cGy prophylactic cranial and 3,000 cGy involved field thoracic radiotherapy. Of the 70 patients, 62 were evaluable for response: 47 patients (76%) achieved an objective response; 14 of 29 patients (48%) with LD had a complete response (CR), with a partial response (PR) plus CR rate of 76%. Seven of 33 patients (21%) with extensive disease (ED) achieved a CR, with a combined PR and CR rate of 76%. Median time to progression (TTP) for all responders was 292 days (42 weeks). Median duration of survival for all LD patients was 415 days (59 weeks). Survival for LD patients was 88% at 6 months, 61% at 12 months, and 29% at 18 months. Median survival duration for all patients in the study was 311 days (44 weeks), with a survival of 79% at 6 months, 44% at 1 year, and 16% at 18 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3 or 4 infection occurring in 33% of patients. Two patients died of pneumonia, one complicated by renal failure, and another suffered cardiac arrest related to treatment. The high activity of this drug combination justifies its use as a first-line treatment of previously untreated SCLC.

Teniposide (VM-26) and carboplatin as initial therapy for small cell lung cancer.

Forty-four patients with previously untreated histologically proven small cell lung cancer (SCLC) were treated with a combination of teniposide 60 mg/m2 intravenously (IV) on days 1 through 5 and carboplatin 400 mg/m2 IV on day 1 every 28 days for six courses. Patients with limited disease (LD) subsequently received prophylactic cranial and thoracic radiotherapy. Of the 44 patients, 40 were evaluable for response: 31 (78%) achieved an objective response; 9 of 18 patients (50%) with LD had a complete response (CR), with a partial response (PR) plus CR rate of 78%. Two of 22 patients (9%) with extensive disease achieved a CR, with a combined PR and CR rate of 77%. Median duration of response for all evaluable patients was 253 days (36 weeks). Median duration of survival for LD patients was 368 days (52 weeks). Survival of LD patients was 86% at 6 months, 52% at 12 months, and 26% at 18 months. Median duration of survival for all patients in the study was 275 days, with a survival of 79% at 6 months, 36% at 1 year, and 12% at 18 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3 or 4 infection occurring in 38% of patients. However, no patient died of sepsis or hemorrhage. Treatment was otherwise well tolerated, with no neurotoxicity or nephrotoxicity documented. The high activity of this drug combination justifies its use as first-line treatment of previously untreated SCLC.

Eosinophils cause acute edematous injury in isolated perfused rat lungs.

Eosinophils produce oxidants and other toxic substances and thus have the potential to cause acute lung injury. We found that addition of normal human eosinophils and the respiratory burst stimulant phorbol myristate acetate to isolated perfused rat lungs acute edematous injury as reflected in weight gain and morphologic changes. Lung to body weight ratio (x 10(3) was 16.7 +/- 3.3 in the experimental group with stimulated eosinophils added compared with 4.7 +/- 0.38 for the control group. Morphologic examination showed both epithelial and endothelial damage. This injury was ameliorated by the addition of catalase, which neutralizes hydrogen peroxide produced during the respiratory burst. Lung/body weight ratio in the group with stimulated eosinophils plus catalase was 7.8 +/- 1.1, and the specimens were indistinguishable from control specimens by histopathologic examination. Our results indicate that eosinophils are capable of causing acute lung injury. This injury is mediated, at least in part, by toxic oxygen products.

Needle-guided breast biopsy for mammographic abnormalities in 561 patients.

Between 1977 and 1983, 561 consecutive patients underwent 595 surgical biopsies for suspicious mammographic lesions with negative clinical correlation. The procedure consisted of preoperative needle localization, with or without immediate radiologic examination of the biopsy specimen, depending on the presence or absence of microcalcifications in the mammographic lesion. Eighty-four carcinomas were found. Of these, 60 (71%) were infiltrating carcinoma and 24 (29%) were noninvasive carcinoma. The carcinoma yield was 24.2% in the patients with lesions involving foci of microcalcifications and 9% in those lesions without calcifications. Surgical treatment of infiltrating carcinoma consisted of 39 modified radical mastectomies, 10 (25.6%) of which were associated with positive nodes, 16 partial mastectomies with axillary dissection, 3 (18.7%) of which were associated with positive nodes, and 5 wedge resections. Treatment of noninvasive carcinoma consisted of 19 partial mastectomies with axillary dissection and 5 modified radical mastectomies. None of these were associated with positive nodes. Modified radical mastectomy was used with decreasing frequency. Of the 10 patients with infiltrating carcinoma and positive axillary nodes treated by modified radical mastectomy, 7 had one to three involved nodes and 3 had four or more; of those with positive nodes treated by partial mastectomy, 1 had one to three involved nodes and 2 had four or more. These results confirm the correlation between suspicious mammographic non-clinical lesions and breast carcinoma.

Induction of hyperparathyroidism by radioactive iodine.

External irradiation to the head and neck has been associated with the emergence of hyperparathyroidism, due both to adenoma and hyperplasia since a single case report was published in 1975. A recent report indicates that there may be some association between hyperparathyroidism and radioiodine administered for thyroid disease. Eight patients are presented herein, all female and in middle age, who presented with hyperparathyroidism due to adenoma (six patients) or hyperplasia (one patient who had undergone radioiodine treatment). In three patients, the dose of radioiodine exceeded 30 mCi. The duration of latency ranged from 4 to 20 years. Associated thyroid disease included cancer, colloid nodules, and thyroiditis. All patients became eucalcemic and have remained so. Experimental results that have supported the influence of radioiodine on parathyroid hyperactivity do not appear completely applicable to the human model. It is believed that the low mitotic rate equivalent to low radiosensitivity may have protected the parathyroid gland somewhat from neoplastic change, although the association of thyroid carcinoma and parathyroid adenoma appears to be a significant expression of radiation exposure. It may be the lack of a pituitary-stimulating hormone and the absence of an abscopal mechanism, as illustrated by irradiation to the thyroid, that explains the relative immunity of parathyroid behavior in the face of radioiodine exposure. Regardless of the frequency and validity of the association, it is important to recognize the possibility of the association illustrated by our case reports and scrutinize appropriate patients by intermittent serum calcium sampling, both for confirmation and possible detection of occult hyperparathyroidism.

Evaluation of the oxi/ferm tube system with selected Gram-negative bacteria.

The Oxi/Ferm test system was evaluated for accuracy and reliability for identification of nonfermentative and oxidase-positive fermentative bacteria by using 375 bacterial strains obtained from stock culture and clinical specimens. The Oxi/Ferm system is a compartmentalized tube containing eight media to provide nine biochemical test results. When combined with the oxidase test, the results corresponding to the positive reactions are totaled and the composite number is located in the coding manual to identify the organisms. The 375 isolates studied were evaluated for accuracy of identification, using both the original and revised code manuals. In comparison with the conventional media used, there was 100% correlation in tests for hydrogen sulfide and indole production, over 96% for nitrogen gas, arginine, and urease, over 92% for xylose and dextrose oxidation, and less than 90% for citrate utilization and dextrose fermentation. There was an overall accuracy in identification of 89.3% using the original manual, with accuracy revised slightly upward to 90.7% using the revised manual. There was 100% accuracy in identification with 44.0% of the strains tested (11 species) using the original manual and with 66.1% (16 species) using the revised manual. Thirteen of the 40 original misidentifications and 14 of 35 revised misidentifications resulted from failure to code and were unidentifiable by Oxi/Ferm. The remainder were incorrectly identified or could not be differentiated from closely related strains. Eleven strains of Alcaligenes odorans were correctly identified using the original code, whereas no code was provided in the revised manual. The Oxi/Ferm system is both simple and rapid and is satisfactory for identification of the more common isolates.

Characterization and identification of gram-negative, nonfermentative bacteria.

The morphological and physiological characteristics of 593 strains of nonfermentative, gram-negative bacteria are described. A battery of 46 tests was used to identify and differentiate strains representing 8 genera and 31 species of named and group-designated bacteria. Seven selected amides and organic salts were closely examined to determine their usefulness, individually or as a battery, in characterizing and identifying the organisms. Of these, allantoin and acetamide showed the most promise in differentiating the more commonly occurring organisms from biochemically similar species. Susceptiblilty patterns to 12 antimicrobics also proved useful in differentiation, especially among atypical strains.

Evaluation of the rapid decarboxylase and dihydrolase test for the differentiation of nonfermentative bacteria.

A rapid medium for the detection of lysine and ornithine decarboxylase and arginine dihydrolase activity of 439 strains of gram-negative, nonfermenting bacteria was evaluated and compared with Moeller decarboxylase medium. Results were obtained in 4 to 24 h using the rapid medium, whereas Moeller medium often required extended (3 to 7 days) incubation. There was 100% agreement in the lysine tests with both media and almost 100% agreement in the ornithine tests. There was 91% agreement in the arginine tests, with the significance of discrepant results discussed. The sensitivity, specificity, and quick results obtained by the rapid test make it a suitable substitute for Moeller medium for the identication of gram-negative, nonfermenting bacteria.