Assessment of pediatric hydronephrosis using output efficiency.

UNLABELLED: Diagnosing obstruction in pediatric patients with hydronephrosis, and renal impairment is often difficult. Renal output efficiency (OE) is a parameter that may improve diagnostic accuracy by allowing normalization of washout according to renal function. The aims of this study were to define a normal range for OE in infants and children and to evaluate its diagnostic accuracy in cases with hydronephrosis. METHODS: Seventy-four children (91 hydronephrotic kidneys; median age, 4 mo; 22 girls and 52 boys) underwent 99mTc-labeled mercaptoacetyl-triglycine scintigraphy using intravenous volume expansion (15 ml/kg normal saline), furosemide diuresis and urethral catheterization, if vesicoureteric reflux was present. Images were interpreted by consensus of two or more experienced observers using visual assessment of the images, differential function and clearance half-time after furosemide (T(1/2)), as well as OE. The final diagnosis was based on surgical findings (n = 23 kidneys) or follow-up for >12 mo (n = 68). RESULTS: Final diagnosis in 22 of the 91 hydronephrotic kidneys was obstruction at the pelviureteric (n = 21) or vesicoureteric (n = 1) junction and no obstruction in the remaining 69. The overall diagnostic accuracy of OE was 89%. Using exhaustive search multivariate logistic regression analysis, only reduced OE (p < 0.001) and decreased renal uptake by visual assessment (p = 0.058) were independently predictive of obstruction (R2 = 0.726). In dilated but unobstructed kidneys, mean OE was 93% +/- 7.1%. In the normal kidneys, mean OE was 96% +/- 3.1%. CONCLUSION: OE improves the diagnostic accuracy of diuretic renography in children and neonates with hydronephrosis and suspected obstruction. Output efficiency should exceed 89% in normal kidneys and 79% in unobstructed, hydronephrotic kidneys.

Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer.

BACKGROUND: Surgical resection of lung cancer remains the treatment of choice in appropriately staged disease, but conventional imaging techniques have limitations. Positron emission tomography (PET) may improve staging accuracy. METHODS: We studied whole body and localized thoracic PET in staging lung cancer. Standardized uptake value was calculated for the primary lesion. Ninety-seven patients under consideration for surgical resection were included. PET, computed tomography, and clinical staging were compared to stage at operation, biopsy, or final outcome. Mean follow up was 17.5 months. RESULTS: PET detected all primary lung cancers with two false-positive primary sites. Sensitivity and specificity for N2 and N3 mediastinal disease was 20% and 89.9% for computed tomography and 70.6% and 97% for PET. PET correctly altered stage in 26.8%, nodal stage in 13.4%, and detected distant metastases in 16.5%. PET missed 7 of 10 cerebral metastases. PET altered management in 37% of patients. PET staging (p<0.0001) and standardized uptake value (p<0.001) were the best predictors of time to death apart from operative staging. CONCLUSIONS: PET provides significant staging and prognostic information in lung cancer patients considered operable by standard criteria. Routine use of PET will prevent unnecessary operation and may be cost effective.

[(18)F]Fluorodeoxyglucose positron emission tomography and its prognostic value in lung cancer.

OBJECTIVE: Positron emission tomography (PET) is being increasingly used as an accurate and non-invasive modality in diagnosis, staging and post-therapy assessment in patients with lung cancer. In this study, we examine whether the uptake of [(18)F]fluorodeoxyglucose (FDG), a marker of increased glucose metabolism in neoplastic cells, is of prognostic value in patients with primary lung cancer. METHODS: We have retrospectively analyzed 77 patients (mean age, 63. 0 years; male/female ratio, 53:24) with primary lung cancers who underwent whole body and localized thoracic PET as part of their diagnostic and staging procedures prior to consideration of surgical resection. The standardized uptake value (SUV) of injected FDG for each primary lesion was correlated with tumour histology and the patient's clinical outcome. RESULTS: A SUV of 20 or greater was found to be of significant prognostic value. The chance of survival (with 95% confidence intervals (CI)) at 12 months post-surgery for the various SUV groups was as follows: 75.2% (59.6-85.5) for SUV<10; 67.5% (29.0-88.2) for SUV 10-<12; 63.6% (29.7-84.5) for SUV 12-<15; 66.7% (19.5-90.4) for SUV 15-<20; 16.7% (0.01-0.52) for SUV>20. A SUV of 20 or more is associated with a 4.66 times increase in hazard, compared with lower levels of SUV. We found no significant correlation between tumour histology and SUV. CONCLUSION: We have previously reported on the significant advantages of PET in the staging and surgical care of patients with lung cancer. The present study adds further support for an additional prognostic role for PET in the management of thoracic malignancy as determined by the amount of labelled-FDG taken up by the primary lesion.

Anaplastic spindle-cell squamous carcinoma arising in association with tall-cell papillary cancer of the thyroid: A potential pitfall.

Transformation of a differentiated thyroid carcinoma is an infrequent occurrence and is usually associated with a dismal prognosis. Following a long-standing history of papillary carcinoma of the thyroid, the patient in the present report developed anaplastic thyroid carcinoma. The anaplastic component initially arose in the setting of papillary carcinoma with tall-cell features, represented a very small proportion of the tumor, and was overlooked at the time of the original diagnosis. Several years later, the patient developed a recurrent neck mass. Fine-needle aspiration (FNA) of this mass revealed a population of atypical spindle cells arranged singly and in papillary clusters which lacked the classical cytologic features of papillary carcinoma of the thyroid. Histology of the resected mass revealed an unusual and recently described subtype of thyroid carcinoma, termed "anaplastic spindle-cell squamous carcinoma," which has been reported as occurring in association with tall-cell papillary carcinoma. The FNA findings of this unusual subtype of anaplastic thyroid carcinoma are presented. Diagn. Cytopathol. 1999;21:413-418.

Comparison of dietary 25-hydroxycholecalciferol and cholecalciferol in broiler chickens.

We conducted a series of 10 feeding trials involving over 36,000 broilers. The effects of various dietary levels of cholecalciferol (vitamin D3) or 25-hydroxycholecalciferol (25-OH-D3) were compared using a "basal" dosage level of 69 micrograms/kg feed, as well as levels ranging from .5 to 1.5 times the basal level. For all 10 studies, average body weight increased by an average of .042 +/- .03 kg (P < .001) and adjusted feed efficiency decreased (improved) by an average of .026 +/- .0046 kg/kg (P < .001) in birds fed 25-OH-D3 in comparison to those fed vitamin D3 at the basal level. Changes in mortality were not detected. Evaluation of different dietary levels of 25-OH-D3 revealed a significant dose-response relationship, with maximal effects on weight gain, feed efficiency, and breast meat yield being observed in the range of 50 to 70 micrograms/kg feed. Preliminary studies with different levels of vitamin D3 suggested no additional benefits on weight gain or feed efficiency with higher dietary levels of vitamin D3. Serum 25-OH-D3 concentrations increased more rapidly in birds fed 25-OH-D3 than in birds fed vitamin D3. There were significant correlations with body weight, feed conversion, and serum 25-OH-D3 concentrations, with no correlations observed between serum 1,25-(OH)2D3 concentrations and these variables.

The use of positron emission tomography and computed tomography in the assessment of trismus associated with head and neck malignancy.

The assessment of head and neck cancer has traditionally involved clinical examination and anatomical imaging by computed tomography (CT) or magnetic resonance imaging (MRI). We present a case where a problem of clinical confusion and inconclusive radiology was resolved by the use of positron emission tomography (PET) coregistered with CT.

Rapid isolation of yeast nuclei.

A procedure has been developed for the rapid isolation of yeast nuclei in high yield using Percoll gradients. The nuclei are substantially free of cytoplasmic contamination as measured by alcohol dehydrogenase activities, have the typical chromatin digestion pattern when digested with nucleases, are useful for isolation of nuclear proteins and for in vitro transcription experiments.

Fluctuation in polyadenylate size and content in exponential- and stationary-phase cells of Saccharomyces cerevisiae.

Stationary-phase cells of Saccharomyces cerevisiae were found to have a reduced polyadenylate [poly(A)] content as compared with exponential-phase cells. A sizing procedure for poly(A) was devised to distinguish between alternative hypotheses to explain this reduction. Two major size classes of poly(A) were found. The decreased representation of the larger of the two classes accounted for the majority of the poly(A) loss. The remainder of the loss was accounted for by fewer poly(A)-containing sequences. The smaller of the two poly(A) classes was apparently not of mitochondrial origin and may be added transcriptionally.

Chemical composition of nucleosomes among domains of calf thymus chromatin differing in micrococcal nuclease accessibility and solubility properties.

Calf thymus chromatin was fractionated by the Sanders' procedure ((1978) J. Cell Biol. 79, 97-109). this procedure involves sequential elutions of micrococcal nuclease-digested nuclei with buffers of increasing ionic strength. Through the use of the nuclei nick translation technique of Levitt et al. (Levitt, A., Axel, R., and Cedar, H. (1979) Dev. Biol. 69, 496-505) which specifically labels the transcriptionally competent regions of the chromosome, the lowest salt eluted, micrococcal nuclease-sensitive chromatin fraction, was found to be enriched in transcriptionally competent chromatin. This chromatin fraction contained approximately equimolar amounts of the core histones and low amounts of histone H1. In addition, this fraction was enriched both in the acetylated species of histone H4 and in the high mobility group (HMG) proteins 14 and 17, but it was depleted in 5-methylcytosine. As the ionic strength of the elution buffers increased, chromatin fractions from less micrococcal nuclease-sensitive chromatin domains were eluted. The nuclease-insensitive fractions were enriched in the unacetylated species of histone H4, 5-methylcytosine, and histone H1. Although these fractions had a smaller proportion of nucleosomes containing HMG-14 and HMG-17, they contained about 50% of the total HMG-14 and HMG-17 population.

The incidence of left iliac fossa uptake of (99m)Tc-DTPA in renal scanning.

In rare cases, extrarenal uptake of technetium-99m diethylenetriamine penta-acetic acid ((99m)Tc-DTPA) has been reported, e.g. in tumours or abscesses. Although in our experience a relatively common occurrence, increased uptake in the left iliac fossa (LIF) and its incidence have not been described. This retrospective study set out to establish the incidence of this phenomenon and to exclude malignancy as the cause. All patients who had a renal (99m)Tc-DTPA scan between 1 January 1996 and 31 December 1997 had their scans reviewed. Presence and grade of increase in iliac fossa activity were determined by consensus agreement of three observers. The list of patients with increased uptake was cross-referenced against the New South Wales (Australia) Cancer Council database to exclude the possibility of a neoplastic lesion in this region. Increased LIF uptake was noted in 41 of the 231 (18%) consecutive patients (18 men, 23 women; mean age 43 years, range 20-83). Among these 41 patients, uptake was severe in 2 (5%), moderate in 12 (29%) and mild in 27 (66%). No patient had increased uptake in the right iliac fossa. Only one patient had a malignant lesion but this was excluded as being the cause of LIF uptake. No other patient developed malignancy (mean follow-up time 4.1 years; range 3.2-5.1). Increase in LIF uptake is a common, benign finding most likely due to activity within the descending colon. It occurs in approximately 18% of the population, and it is important to recognise such uptake in order to avoid misdiagnoses.

On the usefulness of brain PET scanning to the paediatric neuro-oncologist.

Positron emission tomography (PET) scanning adds a functional dimension to brain scanning; levels of metabolic activity are imaged and this information may complement the more "anatomic" imaging of CT and MRI. In a series of 10 young patients the usefulness of PET scanning technique was investigated. The major areas of usefulness were the distinction of posttreatment sequelae from active tumour (both postsurgical MRI changes from tumour and postradiation MRI changes from tumour) and the localization of persisting tumour amenable to radiosurgical treatment. The technique was beneficial in assessing continuing activity in pineal tumours (residual pineal teratoma mass and residual pineocytoma mass) and in assessing activity in brainstem/cerebellar peduncle gliomas (three cases). In one unusual case of widespread leptomeningeal melanoma, the PET scan under-read the situation.

Gliomatosis cerebri: disconnection of the cortical grey matter, demonstrated on PET scan.

18-FDG and 11C methionine PET scans were performed on two patients with gliomatosis cerebri. The cortical grey matter was hypometabolic when compared with normal. The findings support the concept that the cerebral cortex becomes functionally disconnected in this disease owing to the infiltrative nature of the underlying tumour. This may account for the high incidence of dementia in the course of this disease. In one of the cases described here, there was clear evidence of progression from a discrete tumour mass of glioma to gliomatosis cerebri and this progression argues against the WHO classification of this disorder separately from glioma.

Post-transcriptional modification of the poly(A) length of galactose-1-phosphate uridyl transferase mRNA in Saccharomyces cerevisiae.

Thermal elution poly(U)-Sepharose chromatography was utilized to fractionate yeast mRNA based on poly(A) size. Analysis of the in vitro translation products of the fractionated RNAs in a wheat-embryo cell-free protein synthesis system shows a heterogeneous but equal distribution of these abundant translatable mRNAs in the different poly(A) size classes. By comparing the translational activity of inducible galactose-1-phosphate uridyl transferase mRNA, which can be monitored as a function of age, to contitutive mRNAs, we demonstrate that initially galactose-1-phosphate uridyl transferase mRNA has a uniformly large poly(A) tail which becomes heterogeneous and shorter with age in the cytoplasm. These observations are consistent with the previously observed cytoplasmic poly(A) catabolism in yeast and with cytoplasmic post-transcriptional modification of the poly(A) length of galactose-1-phosphate uridyl transferase mRNA.

Randomized clinical trial of aztreonam and aminoglycoside antibiotics in the treatment of serious infections caused by gram-negative bacilli.

Aztreonam was compared with aminoglycoside antibiotics (tobramycin and amikacin) in a randomized, prospective, clinical trial in serious infections caused by gram-negative bacilli (GNB). A total of 43 evaluable patients with 47 infected sites were treated with aztreonam, and 41 evaluable patients were treated with aminoglycosides for 43 infections. Of patients treated with aztreonam, 17 were bacteremic, as were 12 of those treated with aminoglycosides. Clinical and microbiologic response rates were similar, except that only 5 of 11 patients with pneumonia were considered to be clinically cured with aminoglycoside therapy, while 5 of 6 patients with pneumonia treated with aztreonam were cured. Renal impairment was observed in 9 of 54 patients who received aminoglycoside antibiotics, but in only 2 of 53 patients treated with aztreonam. Hearing impairment developed in one patient treated with tobramycin. Transient elevations of serum transaminase levels occurred in 9 of 53 patients treated with aztreonam and in only 2 of 54 aminoglycoside-treated patients. Diarrhea and superinfection occurred with equal frequency in both groups. Serum concentrations of bactericidal activity could not be correlated with the outcome of therapy. Aztreonam appears to have comparable clinical efficacy with aminoglycoside antibiotics for the treatment of serious infections caused by aerobic and facultative GNB. Its use as a single agent for the treatment of serious lower respiratory infections caused by GNB warrants further evaluation.

Cryptococcal pneumonia in AIDS: is cryptococcal meningitis preceded by clinically recognizable pneumonia?

Identification of cryptococcal infection while it is still in its pulmonary phase might improve the prognosis for patients with AIDS who contract cryptococcosis. Since cryptococcal pneumonia is infrequently diagnosed in the AIDS patient, especially compared with the frequency of diagnosis of cryptococcal meningitis, this retrospective study was designed to investigate the frequency of pulmonary complaints in the months before diagnosis of cryptococcal meningitis. The medical records of 18 patients diagnosed with cryptococcal meningitis were analyzed. Of 18 patients, 14 (78%) had respiratory symptoms during the 4-month period before meningitis appeared, as compared with nine of 18 (50%) at the time of diagnosis and four of 16 (25%) in the 4 months following diagnosis. Seven of the 14 cases of pulmonary disease prediagnosis were of unknown etiology; three were eventually diagnosed as cryptococcal infections during evaluation of the meningitis. The remaining eight infections were attributed to bacteria, respiratory viruses, or Pneumocystis carinii, although three of these cultures also contained yeast, presumed to be Candida species, which were not further examined. Our data suggest the importance of singling out AIDS patients who may have pulmonary cryptococcosis. Cryptocococcsis should be included in the differential diagnosis of pulmonary infection in HIV-positive patients with CD4+ lymphocyte counts < 200/mm3, and full identification of yeasts recovered from sputum or bronchoalveolar lavage fluid cultures should be done. A larger study should be undertaken to better define the incidence of clinically recognizable pulmonary cryptococcosis in AIDS patients.

Histone modifications in the yeast S. Cerevisiae.

The content of the acetylated histone species associated with the highly transcriptionally active chromatin of yeast was examined. We found yeast chromatin to contain very high levels of the acetylated species for histones H3, H4 and possibly the H2B variants, H2B-1 and H2B-2. Sixty-three percent of the histone H4 species was represented by the di-, tri- and tetra-acetylated forms. These results make yeast chromatin among the most highly acetylated of any chromatins reported thus far. In addition, the results are consistent with the idea that hyperacetylation of histones allows chromatin to be transcribed at an increased rate.

Treatment of AIDS and AIDS-related complex with 2',3'-dideoxyinosine given once daily.

In a phase I dosage-finding trial, 2',3'-dideoxyinosine (didanosine; ddI) was administered once daily to 36 patients with AIDS or AIDS-related complex for up to 65 weeks (mean, 32.1 weeks) at six dosage levels. Thirteen of 18 patients previously treated with zidovudine had developed hematologic intolerance. The maximal tolerated dosage of ddI was 12 mg/(kg.d); dose-limiting toxicities were pancreatitis and peripheral neuropathy. Other toxicities included elevation in hepatic transaminase levels, rash, cardiac conduction abnormality, and asymptomatic hyperuricemia. Eighty-six percent of patients who completed 6 weeks of treatment showed improvement in constitutional symptoms and significant weight gain. In patients treated with ddI, the mean number of CD4+ lymphocytes increased from 124/mm3 at baseline to 199/mm3 at 24 weeks (P = .0027) and the mean leukocyte count, total lymphocyte count, and hemoglobin level showed increases (all P less than .01) after 12 weeks. Serum levels of viral p24 antigen decreased greater than or equal to 50% in 14 of 19 assessable patients. No differences between the responses of patients previously treated with zidovudine and those of zidovudine-naive patients were observed. These results indicate that ddI has significant antiretroviral activity in vivo and a toxicity profile different from that of zidovudine.

Once-daily administration of 2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. Results of a Phase I trial.

We conducted a Phase I open-label trial of 2',3'-dideoxyinosine (ddI) for the treatment of the acquired immunodeficiency syndrome (AIDS) and severe AIDS-related complex. A single daily dose of ddI was administered orally to 34 patients (17 with AIDS and 17 with AIDS-related complex) for a median of 12 weeks (range, 2 to 56). We studied six dose levels from 1.6 to 30.4 mg per kilogram of body weight per day. Of the 17 patients previously treated with zidovudine, 13 had had hematologic side effects. The maximal tolerated dose of oral ddI was estimated to be 20.4 mg per kilogram per day. Pancreatitis and peripheral neuropathy were the major dose-limiting toxic effects. Other toxic effects included elevations in hepatic transaminase levels, abnormalities in cardiac conduction, rash, and asymptomatic elevations in serum urate levels and the creatine kinase fraction from skeletal muscle. Treatment with ddI was associated with an increase in the mean number of CD4 lymphocytes from 125 per cubic millimeter at base line to 182 per cubic millimeter after 10 weeks (P = 0.005). There were also increases after 12 weeks in the mean total lymphocyte count (from 0.8 to 1.2 x 10(9) per liter) and the mean hemoglobin level (from 12.9 to 14.1 g per deciliter) (both P less than 0.01). The amount of human immunodeficiency virus p24 antigen decreased by more than 50 percent in 14 of 19 patients with detectable antigen. No differences in response were observed between patients previously treated with zidovudine and those never treated with the drug. We conclude that ddI has antiretroviral activity in patients with AIDS or AIDS-related complex and that the toxicity of ddI differs from that of zidovudine. However, controlled trials are necessary to evaluate the efficacy of ddI.