Cross-Country Comparison of School Neighborhood Food Environments in Houston, Texas and Guadalajara, Mexico.

Studies in the U.S. and Mexico have observed the clustering of food resources around schools, which may promote the use of these resources. Our study characterized and compared school neighborhood food environments in Guadalajara, Jalisco, and Houston, Texas, and examined socioeconomic disparities in food resource availability across school neighborhoods. We used the Goods and Services Inventory to document the frequency and type of resources within each school neighborhood. School neighborhoods in Guadalajara had significantly more food resources than those in Houston. We found that convenience stores and table service restaurants were the most prevalent food resources in school neighborhoods in both cities. Guadalajara school neighborhoods had a higher prevalence of supermarkets and grocery stores than Houston. Low-income school neighborhoods in Guadalajara with poorly educated residents had significantly more food carts than high-income neighborhoods with more educated residents. In Houston, we found significantly more fast food restaurants and convenience stores in school neighborhoods with more educated residents than school neighborhoods with less educated residents. The influence of food resources within school neighborhoods on the dietary habits of schoolchildren should be further explored in both the U.S. and Mexico. The characterization of school neighborhood food environments can inform policymakers, city planners, and school officials who seek to implement policies to create healthier food environments.

Accessory Vein Obliteration and Balloon-Assisted Maturation for Immature Arteriovenous Fistulas for Haemodialysis: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to examine outcomes of immature arteriovenous fistula salvage using balloon angioplasty (PTA) without and with accessory vein obliteration (PTA + VO). MATERIALS AND METHODS: PubMed and Embase were accessed on 21 September 2020 to retrieve cohort studies on adult patients with end-stage renal failure (ESRF) requiring dialysis. Risk of bias was assessed using Newcastle-Ottawa Scale. Studies were pooled into PTA or PTA + VO arms, with outcomes (technical/clinical success, primary/secondary post-intervention patency until 12 months) reported as event rates with 95% confidence intervals. Random-effects model and maximum likelihood meta-regression were used for meta-analysis. RESULTS: Fourteen studies (1030 participants) were included. The between-subgroup difference in outcomes was largely non-significant (p > 0.050). CONCLUSION: The evidence does not support balloon angioplasty with concomitant accessory vein obliteration for immature fistula salvage.

The size of suspended particulate matter in air.

By means of the NASN cascade impactor the particle sizes of ambient aerosols can be measured by fractionating the particles according to their aerodynamic dimensions, and the fractions can be quantified gravimetrically. Data obtained with this instrument show that particulate matter suspended in urban air in the United States and Great Britain is remarkably uniform in distribution and that the particles are predominantly less than 1 microm in diameter. In Ankara, Turkey, the high proportion of particles larger than 1 microm in diameter are associated with the incomplete combustion of lignite; particulate concentrations in Ankara, however, are considerably higher than those measured elsewhere. The growth of particles in air during temperature inversions occurs in Cincinnati; the greater proportion of large particles found there during inversion periods can account for the reduction in visibility. Aerosols in the vicinity of highways are composed of particles larger than those found some distance away because of the reentrainment of debris by the traffic-induced turbulence. On the other hand, highway configuration and traffic volume have little effect on the size distribution of aerosols in samples collected away from the turbulence area of the roadway. Aerosols measured inside buildings are predominantly smaller in size and exhibit a narrower range of sizes than aerosols outside buildings.

Tubules of globoid leukodystrophy: a right-handed helix.

Morphologic similarity between the cytoplasmic tubules of globoid leukodystrophy and Gaucher's disease (as demonstrated by thin sectioning, negative staining, and shadowing techniques) and their resemblance to negatively stained beef cerebroside are presented as evidence favoring the accumulation of cerebrosides in globoid cells. The tubules of globoid leukodystrophy have a 60-angstrom periodic banding similar to the tubules of Gaucher's disease. A right-handed helical twisting of the tubules is observed in both diseases.

A rapid cold-hardening process in insects.

Traditionally studies of cold tolerance in insects have focused on seasonal adaptations related to overwintering that are observed after weeks or months of exposure to low temperature. In contrast, an extremely rapid cold-hardening response was observed in nonoverwintering stages that confers protection against injury due to cold shock at temperatures above the supercooling point. This response was observed in nondiapausing larvae and pharate adults of the flesh fly, Sarcophaga crassipalpis, nondiapausing adults of the elm leaf beetle, Xanthogaleruca luteola, and the milkweed bug, Oncopeltus fasciatus. The rapid hardening response is correlated with the accumulation of glycerol.

Interactions between entorhinal axons and target hippocampal neurons: a role for glutamate in the development of hippocampal circuitry.

A coculture system consisting of input axons from entorhinal cortex explants and target hippocampal pyramidal neurons was used to demonstrate that glutamate, released spontaneously from afferent axons, can influence both dendritic geometry of target neurons and formation of presumptive synaptic sites. Dendritic outgrowth was reduced in hippocampal neurons growing on entorhinal axons when compared with neurons growing off the axons. Presumptive presynaptic sites were observed in association with hippocampal neuron dendrites and somas. HPLC analysis showed that glutamate was released from the explants in an activity- and Ca2(+)-dependent manner. The general glutamate receptor antagonist D-glutamylglycine significantly increased dendritic outgrowth in pyramidal neurons associated with entorhinal axons and reduced presumptive presynaptic sites. Tetrodotoxin and reduction of extracellular Ca2+ also promoted dendritic outgrowth and reduced the formation of presumptive synaptic sites. The results suggest that the neurotransmitter glutamate may play important roles in the development of hippocampal circuitry.

Functional phosphorylation sites in the C-terminal region of the multivalent multifunctional transcriptional factor CTCF.

CTCF is a widely expressed and highly conserved multi-Zn-finger (ZF) nuclear factor. Binding to various CTCF target sites (CTSs) is mediated by combinatorial contributions of different ZFs. Different CTSs mediate distinct CTCF functions in transcriptional regulation, including promoter repression or activation and hormone-responsive gene silencing. In addition, the necessary and sufficient core sequences of diverse enhancer-blocking (insulator) elements, including CpG methylation-sensitive ones, have recently been pinpointed to CTSs. To determine whether a posttranslational modification may modulate CTCF functions, we studied CTCF phosphorylation. We demonstrated that most of the modifications that occur at the carboxy terminus in vivo can be reproduced in vitro with casein kinase II (CKII). Major modification sites map to four serines within the S(604)KKEDS(609)S(610)DS(612)E motif that is highly conserved in vertebrates. Specific mutations of these serines abrogate phosphorylation of CTCF in vivo and CKII-induced phosphorylation in vitro. In addition, we showed that completely preventing phosphorylation by substituting all serines within this site resulted in markedly enhanced repression of the CTS-bearing vertebrate c-myc promoters, but did not alter CTCF nuclear localization or in vitro DNA-binding characteristics assayed with c-myc CTSs. Moreover, these substitutions manifested a profound effect on negative cell growth regulation by wild-type CTCF. CKII may thus be responsible for attenuation of CTCF activity, either acting on its own or by providing the signal for phosphorylation by other kinases and for CTCF-interacting protein partners.

Are routine peritoneal fluid cultures during appendicectomy justified?

BACKGROUND: To determine the impact of obtaining routine peritoneal fluid cultures during appendicectomy, on the treatment and the clinical outcomes. METHODS: The case notes of 137 consecutive patients having appendicectomy, selected from the microbiology database over a period of 1 year were reviewed. The microorganisms in peritoneal cultures, selection of antibiotics and clinical outcomes were recorded. Patients were subdivided into two groups; group I: uncomplicated appendicitis and group II: complicated appendicitis. RESULTS: The study included 137 patients with a median age of 19 years. Cultures were obtained from 79.5% of patients (group I: 67/84, group II: 42/53). Cultures were positive in 28.3% (19/67) patients in group I and 69% (29/ 42) in group II. Wound infection (5.6%), prolonged ileus (7.5%) and intra-abdominal abscess (3.7%) were the recorded complications in group II. Antibiotics were modified in 3 out of 109 patients. CONCLUSION: Intra-operative peritoneal cultures during appendicectomy do not significantly contribute towards patient management.

Mutagenic mucus in the cervix of smokers.

A pilot study was conducted to determine whether any relationship exists between mutagenicity of a women's uterine cervical mucus and her current smoking status. Cervical fluids obtained from 78 premenopausal women seen between July 1983 and March 1984 at the University of California, San Francisco Dysplasia (and diethylstilbestrol) Clinic or in a private practice were tested for mutagenicity by means of the Ames-Salmonella microsomal test. Of 36 current smokers, 14 (39%) had positive tests as compared to 5 of 42 nonsmokers (12%). The odds ratio (OR) estimate was 4.7 with 95% confidence limits (CL) of 1.6-14.2. Secretions from 14 of 32 (44%) women who had smoked during the day of the sample collection--within the previous 7 hours--were positive on the laboratory test, whereas none of the 4 women was positive who had smoked 8 hours or more before the specimens were obtained. Fluids from women with dysplasia or carcinoma in situ were more likely to be mutagenic than were those from other women, although this finding may be due to chance (OR = 2.0 with 95% CL of .70-5.9). This relationship between smoking and mutagenic cervical fluids offers evidence that might help to explain the association between cervical cancer and cigarette smoking noted in previous epidemiologic studies.

Murine monoclonal antibodies against carcinoembryonic antigen: immunological, pharmacokinetic, and targeting properties in humans.

We have examined three 131I-labeled murine monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA), NP-2, NP-3, and NP-4, after i.v. injection in patients with diverse cancers. Although the MAbs had a similar tumor-targeting ability, several important features were discovered that have led us to the selection of one of these MAbs for further clinical evaluation. We found that it is important to evaluate MAbs with a high immunoreactivity. For example, the MAb NP-2 was used initially in patients with an immunoreactivity between 35 and 50%. Although the tumor-imaging properties of this MAb compared favorably with the affinity-purified, goat anti-CEA antibody that we used previously, further purification of NP-2 to an immunoreactivity greater than 70% uncovered a previously unknown cross-reactivity with human granulocytes. It was also discovered that the MAbs differed in their ability to complex with CEA in the blood. Plasma samples were analyzed by gel filtration at 1 or 24 h after injection. The formation of complexes with circulating CEA was dependent on the CEA:MAb ratio in the blood. NP-3 complexed to a greater degree with CEA than NP-4, but NP-2 did not complex with CEA even at CEA:NP-2 ratios of 55 to 1. NP-3 commonly showed enhanced uptake in the colon by external scintigraphy, and examination of the radioactivity in the stool showed that most of the radioactivity was associated with whole IgG and large-sized fragments of NP-3. We also compared the rate of elimination of radioactivity from the blood for all of the MAbs and compared the clearance of NP-3 to NP-4 at three different ranges of MAb protein doses (less than 1.0 mg, 1 to 5 mg, and 5 to 20 mg). The blood clearance rate for NP-3 was fastest among the other MAbs at protein doses exceeding 1.0 mg. Patients given less than 1.0 mg of NP-4 had a significantly (P less than 0.005) shorter elimination half-life than patients given more than 1.0 mg of NP-4. By virtue of NP-4's good targeting properties in patients and its limited complexation with circulating CEA, it was selected as the MAb of choice for CEA tumor imaging.

Tumor, red marrow, and organ dosimetry for 131I-labeled anti-carcinoembryonic antigen monoclonal antibody.

Tumor-, red marrow-, and organ-absorbed doses were calculated for patients receiving 131I-labeled monoclonal antibodies against carcinoembryonic antigen for either diagnosis or therapy. Ten patients with confirmed liver tumors who received doses ranging from 10.79 to 200 mCi were evaluated. Urine and blood samples were taken in order to determine total body and red marrow activity, respectively. Anterior and posterior gamma camera images were obtained at multiple times postinjection in order to quantitate activity uptake using the conjugate view counting method for the following organs and regions: lungs, liver, spleen, kidneys, and the liver tumors. In addition, sacral regions of interest were drawn to generate red marrow-absorbed dose estimates for comparison to those obtained by blood sampling. Tumor volumes were obtained from volumetric analysis of the patient's computed tomographic study and tumor S values were obtained by assuming uniform distribution of the 131I-labeled monoclonal antibody in spherical tumor regions considering all emitted electrons, beta-particles, and photons. The following mean absorbed doses in rads/mCi injected were obtained: lungs, 2.3 +/- 1.6 (SD); liver, 1.4 +/- 0.7; spleen, 2.6 +/- 1.4; kidneys, 3.1 +/- 1.5; total body, 0.7 +/- 0.5; red marrow from blood sampling, 2.9 +/- 1.9; red marrow from sacral scintigraphy, 1.7 +/- 1.2; and liver tumors, 69.3 +/- 92.5. Tumor volumes ranged from 1 to 216 g and the percentage of uptake/g of monoclonal antibody into these tumors ranged from 0.0006 to 1.040. There was a statistically significant difference between the two techniques for estimation of red marrow dose (P less than 0.01). This methodology, permits calculation of tumor, red marrow, and organ dosimetry using planar gamma camera imaging.

Clinical studies of cancer radioimmunodetection with carcinoembryonic antigen monoclonal antibody fragments labeled with 123I or 99mTc.

Seventy-three patients with diverse cancers containing carcinoembryonic antigen received 123I-labeled anti-carcinoembryonic antigen monoclonal antibody F(ab')2 fragment [38 patients], 99mTc-labeled anti-carcinoembryonic antigen monoclonal antibody Fab' fragment [23 patients], or both reagents at different times [6 patients] for evaluation of antibody targeting and imaging [radioimmunodetection (RAID)], using planar and single-photon emission computed tomography. The results indicated that antibody fragments are preferred for early tumor imaging (within 24 h). Rapid targeting and clearance from blood and normal organs of the antibody fragments (blood median t1/2 elimination of 26.5 and 13.2 h for the F(ab')2 and Fab' fragments respectively) permitted the use of short-lived radionuclides, such as 123I (13.3 h) and 99mTc (6 h), and confirmed that selective antibody accretion in tumors occurred very soon after administration, such as between 2 and 5 h. Scan interpretations at 24 h for the 123I-labeled F(ab')2 and at 2-5 h for the 99mTc-labeled Fab' revealed overall sensitivities, on a tumor site basis, of 95.9 and 94.9%, respectively. On a site basis, the overall accuracies were 94.2 and 93.8% for the 123I and 99mTc immunoconjugates, respectively. In the 6 patients studied with both radioimmunoconjugates, a high concordance in detection was found. Both imaging agents also revealed a high number of putatively new tumor sites not disclosed by other radiological methods at the time of the RAID studies, of which 40.0 and 20.5% were subsequently confirmed as tumor for the 123I and 99mTc agents, respectively, within an 11-month follow-up period. This represented 24 proven occult tumor sites in 19 patients given the 123I-immunoconjugate and 16 proven occult tumor sites in 9 patients receiving the 99mTc agent. The new lesions were found up to 17 and 7 months earlier for 123I-RAID and 99mTc-RAID, respectively, than with other detection methods. The smallest tumors identified were below 0.5 cm, especially with the 99mTc immunoconjugate and single-photon emission computed tomography imaging. The findings of this study confirm previous evidence that RAID is a safe and a potentially useful new method of cancer detection. Despite the excellent results with the 123I-F(ab')2 antibody fragment, its poor availability and high cost limit its clinical use. Therefore, the 99mTc agent, which is made by an instant, 1-step, 1-vial, direct labeling method, appears to be the method of choice for rapid and accurate detection of cancer by RAID.

Mycolic acid biosynthesis: definition and targeting of the Claisen condensation step.

Through the use of 2,2-[2H]palmitic acid pulse labeling of the whole cells of C. matruchotti and analysis by gas chromatography-mass spectrometry of the non-labeled and [2H]-labeled corynomycolates, we established a new mechanism for palmitate condensation devoid of the postulated carboxylation step. This evidence allowed the design and synthesis of several structurally related antagonists against the condensation reactions which were shown to possess potent in vivo activity against C. matruchotti with complete inhibition of growth on solid media at concentrations between 1-10 microg/ml. In addition, a cell-free in vitro assay of corynomycolate synthesis was developed to allow the screening of these and other antagonists.

Characterization of the in vitro synthesized arabinan of mycobacterial cell walls.

Previous studies have shown that polymerized [14C]arabinan can be synthesized from polyprenylphosphate-[14C]arabinose by the particulate enzymes of Mycobacterium smegmatis [R.E. Lee, K. Mikusová, P.J. Brennan and G.S Besra (1995) J. Am. Chem. Soc. 117, 11829-11832]. In the present investigation, the [14C]arabinan product was biochemically characterized. Sizing chromatography revealed a molecular weight consistent with that expected from mature arabinan. Digestion of the [14C]arabinan with a mixture of arabinases produced oligo[14C]arabinoside fragments including hexa[14C]arabinoside and tetra[14C]arabinoside which originated from the non-reducing terminal regions of the polymer, and di[14C]arabinoside from the internal regions of the polymer. These arabinoside fragments represent the major known structural motifs that comprise the arabinan segment of arabinogalactan and lipoarabinomannan. The presence of [14C]arabinose in both the internal and external regions of the [14C]arabinan suggests that polyprenylphosphate-arabinose is the major, and perhaps the only, donor of arabinosyl residues in mycobacteria.

Targeting, dosimetry, and radioimmunotherapy of B-cell lymphomas with iodine-131-labeled LL2 monoclonal antibody.

Sixteen patients with non-Hodgkin's lymphoma were infused with 6.2 to 58.2 mCi (0.2 to 3.9 mg) doses of radioactive iodine (131I)-labeled LL2 immunoglobulin G (IgG) or F(ab')2, in order to study antibody distribution, pharmacokinetics, dosimetry, toxicity, tumor targeting, and therapy. LL2 is a murine IgG2a monoclonal antibody (MAb) reactive with B cells and non-Hodgkin's B-cell lymphoma. In a series of five assessable therapy patients, doses as small as 30 mCi 131I-LL2 IgG or F(ab')2 resulted in tumor responses (two partial remissions, two mixed and minor responses, and one no response), while one patient receiving diagnostic doses as low as 6.2 mCi showed a partial remission for 1 year and a complete remission after a second low radiation dose. No acute toxicities were noted, and only myelotoxicity accompanied therapeutic doses, with grade IV marrow toxicity seen in three of seven patients receiving total doses of about 50 mCi. Dosimetry calculations showed spleen and tumor dose rules of about 4.6 cGy/mCi, which was three to four times the dose to other organs. Despite the administration of relatively low doses of LL2 (0.2 to 3.9 mg), 82% of 60 known extrasplenic lymphoma sites were imaged. Serum clearance showed an average distribution half-life (T1/2) of 2.1 hours and an elimination T1/2 of 32.0 hours. The average total-body clearance T1/2 was 43 to 45 hours. LL2's antigenic target does not appear to be shed in high amounts into the circulation. Three of eight patients having at least two injections showed a human antimouse antibody response. These patients may have been presensitized to animal protein. An interesting observation in this study was the marked drop in circulating B lymphocytes after the administration of radioiodinated LL2 or anticarcinoembryonic antigen MAbs, suggesting that this is a nonspecific radiation effect and not necessarily related to the binding of MAb to normal B cells.

A prospective randomized trial evaluating prophylactic antibiotics to prevent triple-lumen catheter-related sepsis in patients treated with immunotherapy.

During a 15-month period, 92 patients undergoing 129 treatment episodes of immunotherapy with interleukin-2 (IL-2) alone or with immune cells underwent insertion of central venous catheters (CVCs) in the Surgery Branch, National Cancer Institute. Before each catheter insertion patients were prospectively randomized into one of three treatment groups; therapy with intravenous (IV) placebo using D5W, IV oxacillin, or change of the catheter to a new site every 72 hours. The mean duration of catheterization was 3.8 +/- 1.1 days. No patient in the oxacillin arm developed catheter-related sepsis, while eight patients in the control arms (five, line change, three, placebo) developed catheter-related sepsis (P2 = .050). Seven episodes of catheter-related sepsis were due to Staphylococcus aureus and one was due to Staphylococcus epidermidis. Catheter colonization was reduced significantly in the oxacillin arm versus control arms (P = .0001). Staphylococcus aureus, Staphylococcus epidermidis, and other coagulase-negative Staphylococci were sensitive to oxacillin in 89%, 60%, and 50% of cultures, respectively. No evidence of bacterial overgrowth, candida colonization, or candidemia was observed in these patients. Thus this trial demonstrates that treatment with prophylactic oxacillin can decrease the incidence of catheter-related sepsis in patients undergoing immunotherapy with interleukin-2 (IL-2). To our knowledge this is the first prospective randomized trial to evaluate the prophylactic use of systemic antibiotics in the prophylaxis of CVC sepsis.

Cardiorespiratory effects of immunotherapy with interleukin-2.

The administration of interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells can mediate the regression of cancer. Treatment with IL-2 is associated with significant cardiorespiratory effects, as well as a leaky capillary syndrome requiring careful fluid management. A mild reversible depression of cardiac function is also associated with IL-2 treatment. All patients treated with recombinant IL-2 alone, with transfer of LAK cells, or with cyclophosphamide between December 1984 and September 1987 (total of 423 treatment courses in 317 total patients) were evaluated as to the development of significant cardiorespiratory toxicity. Of the 423 treatment courses, only 1.8% were associated with severe peripheral edema and only 2.8% and 3.1% respectively, were associated with significant ascites or pleural effusions. Thirty-nine of 423 patients (9.2%) had severe respiratory distress and 27 patients required intubation (6.4%). Cardiovascular effects included tachycardia and hypotension requiring vasopressor administration in 65% and intravenous (IV) fluid administration. Weight gain greater than or equal to 10% of body weight was noted in 32% of the 423 patients. Arrhythmias were primarily supraventricular (9.7%) and responded well to conventional medical treatments. Angina or ischemic changes were noted in 2.6% of patients and myocardial infarction in 1.2%. IL-2 caused peripheral vasodilation, with a significant decrease in peripheral vascular resistance (2,254 +/- 398 v 1,303 +/- 351 dyne.s.cm-5, P less than .0001), and an increase in heart rate (66.2 +/- 10 v 104.3 +/- 9.6 beats/min, P less than .0001). There was also evidence of mild cardiac dysfunction, with a significant decrease in the left ventricular stroke work (LVSW) index (P less than .0001) and ejection fraction (LVEF) (from 58% +/- 10% to 52% +/- 9%, P less than .03). A repeat LVEF performed after 1 to 3 months, had returned to baseline values (60% +/- 10%). A mean 64% increase in the rate of disappearance of radioactive iodine (125I) albumin (P less than .05) consistent with the development of a leaky capillary syndrome was noted. Patients with underlying cardiorespiratory diseases may be at greater risk during IL-2 administration and should not be selected to undergo this treatment.

Shift in subfractions of rat alveolar macrophages in vivo during endotoxin-induced alveolitis.

To elucidate changes in alveolar macrophages that accompany sepsis-induced lung injury, this study analyzed the subfractions of alveolar macrophages (AM) recovered by lung lavage during the onset of endotoxin-induced acute neutrophilic alveolar inflammation in the rat model. Centrifugation on continuous self-generated density gradients of Percoll was used to fractionate AM into subpopulations between density limits 1.012 and 1.130. Two-thirds of AM recovered from pathogen-free control rats (group C) were in a fraction with a density range of 1.058-1.078 ["normal" density fraction, (ND)]. Only 6% were located in a very low density (VLD) fraction 1.037-1.048. Neutrophils accounted for less than 1% of recovered cells and usually were found in the fraction with density range of 1.079-1.130. By contrast, if rats underwent lung lavage 15 hours after the administration of endotoxin (group E), only 38% of macrophages were recovered in the "normal" density fraction, whereas 26% of the AM recovered were in the VLD fraction. This shift in the relative sizes of the density based subpopulations coincided with the onset of acute bronchoalveolar inflammation as indicated by the recovery of neutrophils by bronchoalveolar lavage (PMN = 7 X 10(4) in C, vs. 9.4 X 10(5) in E, p less than .001). The macrophages on the low density subfractions showed functional impairment: they were less viable in culture and migrated poorly in response to endotoxin-activated serum compared to macrophages in the "normal" density fraction from the endotoxin-treated animals. The rapid emergence of the low density population after endotoxin could represent an influx of new cells, but more likely indicates that injury to or previous activation of resident macrophages has caused their density to decrease. We speculate that the emergence of a population of AM in airspaces with low density and impaired function could weaken pulmonary host defence following endotoxemia.

A case of nonneurologic Gaucher's disease that biochemically resembles the neurologic types.

Systemic findings such as hepatosplenomegaly and typical Gaucher storage cells in a bone marrow aspirate led to the clinical diagnosis of Gaucher's disease in the seven-year old patient described in this report. On the basis of the lack of neurologic involvement the child was classified as having the Type 1, nonneurologic form of Gaucher's disease. After splenectomy glucocerebrosidase was extracted from her spleen for biochemical analysis. As expected, a marked deficiency of glucocerebrosidase activity was evident in the splenic extract, however her enzyme displayed anomalous behavior compared to other identical splenic preparations from documented Type 1 Gaucher's disease patients in that it failed to reconstitute with the acidic lipid phosphatidylserine. Using the polymerase chain reaction (PCR)-based color complementation assay and restriction endonuclease analysis, we compared the mutation genotype of this child with that of five other classical Type 1 patients. This analysis revealed that our patient alone was homoallelic for a T----C transition at position 1448 in the glucocerebrosidase cDNA that results in a 444Leu----Pro substitution in the glucocerebrosidase protein. The latter mutation genotype is normally associated with the neurologic phenotype, namely, the Types 2 and 3 forms of the disease. The relevance of the nature of polarity in clinical and biochemical analyses is discussed with regard to the phenotypic classification and the future clinical course of disease in the child.

Delayed leukoencephalopathy in survivors with small cell lung cancer.

Six patients with small cell lung cancer developed a slowly progressive neurologic syndrome characterized by apathy, abulia, memory loss, gait ataxia, and corticospinal tract signs 26 to 50 months (mean, 35.2 months) after prophylactic cranial irradiation and systemic chemotherapy. In each case this was accompanied by CT and/or MRI evidence of changes in the periventricular white matter. These patients are long-term survivors (41 to 69 months) and do not have CNS metastases.