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At least 415 records · Page 23Linked to original sources
PubMed2006

The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia.

OBJECTIVE: Thiopurine metabolism was investigated in children with acute lymphoblastic leukemia treated in the United Kingdom Medical Research Council trial ALL97. This trial compared the efficacy and toxicity of thioguanine (INN, thioguanine) versus mercaptopurine. METHODS: Consecutive children were randomized to receive thioguanine or mercaptopurine during maintenance chemotherapy. Toxicity data were collected by an adverse event-reporting system with follow-up questionnaires. Red blood cell thiopurine methyltransferase (TPMT) activity and thioguanine nucleotide concentrations were measured by standard techniques. RESULTS: Of the children, 748 were randomized to thioguanine and 744 were randomized to mercaptopurine. There was no difference in the event-free survival rate between the 2 groups (80% and 81%, respectively, at 5 years). Thioguanine was associated with veno-occlusive disease (VOD) of the liver in 95 children, and persistent splenomegaly as a result of portal hypertension developed in 43 children. TPMT activity was significantly lower in the children in whom VOD developed, with a median of 13.4 U (range, 5.8-23 U) compared with 15.2 U (range, 5.3-27) in a control group of 161 leukemia patients in whom VOD did not develop (median difference, 1.8 U; 95% confidence interval, 0.9-2.7 U; P = .0001). TPMT activity in children with persistent splenomegaly was also lower than that in control subjects (median difference, 1.6 U; 95% confidence interval, 0.3-2.8 U; P = .012). There was no difference in red blood cell thioguanine nucleotide concentrations. CONCLUSIONS: Thioguanine was associated with liver damage in 11% of children randomized to thioguanine without an improvement in event-free survival rate. The association of lower TPMT activity with thioguanine-related liver damage could provide a means of identifying at-risk patients.

Adolescent↗
PubMed2004

Plasmodium falciparum ookinete invasion of the midgut epithelium of Anopheles stephensi is consistent with the Time Bomb model.

Plasmodium falciparum gametocytes grown in vitro were fed through membrane feeders to laboratory-reared Anopheles stephensi mosquitoes. Intact midguts, including entire bloodmeal contents, were removed between 24 and 48 h post-bloodfeeding. Giemsa-stained histological sections were prepared from the midguts and examined by light microscopy. Contrary to previous reports, ookinetes were clearly visible within midgut epithelial cells, demonstrating intracellular migration across the midgut wall. Ookinetes entered epithelial cells through the lateral apical membrane at sites where 3 adjacent cells converged. There was no evidence for the existence of a morphologically distinct group of epithelial cells preferentially invaded by ookinetes. However, ookinete penetration was associated with significant morphological changes to invaded cells, including differential staining, condensation and fragmentation of the nucleus, vacuolization, loss of microvilli and various degrees of extrusion into the midgut lumen. Epithelial cells completely separated from the midgut wall were found within the midgut lumen. These cells were associated with invading parasites suggesting that ookinete penetration resulted in complete ejection of invaded cells from the midgut wall. Small clusters of morphologically altered midgut cells and invading parasites spanning the membranes of adjacent abnormal epithelial cells were observed, consistent with intracellular movement of ookinetes between neighbouring midgut cells. Extruded epithelial cells were also observed rarely in uninfected midguts. Epithelial cell extrusion, therefore, may be a general mechanism of tissue repair through which damaged cells are removed from the midgut wall rather than a parasite-specific response. These observations demonstrate that human malaria parasite infection of mosquitoes is consistent with, and provides further support for, the Time Bomb model of ookinete invasion of the mosquito midgut epithelium previously proposed for rodent malaria parasites.

Animals↗
PubMed1986

Effects of acute and chronic dosing of NSAIDs in patients with renal insufficiency.

Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to patients with chronically impaired renal function has been reported to cause abrupt and sustained reductions in renal plasma flow (RPF), glomerular filtration rate (GFR), and solute and water excretion in association with decreased renal prostanoid production. However, the time course of these acute effects and whether they are sustained during chronic exposure to the NSAIDs are unknown. Accordingly, using standard clearance and balance techniques, we investigated the effects of acute (zero to four hours) and chronic (five days) oral administration of two different NSAIDs on renal function in patients with stable, mild to moderate chronic renal insufficiency (CRI) and in normal subjects. In patients, acute oral administration of ketoprofen (K) and indomethacin (I) resulted in significant decreases in GFR (K: from 36 +/- 3 to 20 +/- 4 ml/min, P = 0.001; I: from 37 +/- 6 to 30 +/- 7 ml/min, P = 0.032; in RPF (K: from 194 +/- 21 to 146 +/- 21 ml/min, P = 0.002; I: from 222 +/- 33 to 147 +/- 18 ml/min, P = 0.016); and in urinary PGE2 excretion (K: from 0.60 +/- 0.25 to 0.08 +/- 0.02 ng/min, P = 0.05; I: from 0.34 +/- 0.06 to 0.18 +/- 0.06 ng/min, P = 0.042). Fractional excretion of sodium chloride and fractional free water clearance (CH2O/CIn) also decreased significantly after both agents. In normal subjects, GFR and RPF were not significantly decreased after acute dosing, whereas urinary PGE2 and fractional excretions of NaCl and free water decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Silicone lymphadenopathy associated with augmentation mammaplasty. Morphologic features of nine cases.

Silicone lymphadenopathy (SL)--defined as the presence of silicone in a lymph node--is a rare side effect of mammary augmentation either by injection of liquid silicone or by placement of a bag-gel prosthesis. Nine new cases in eight patients are herein reported and compared with six previously well-documented cases. The available data showed that SL was frequently detected as an incidental finding of no clinical significance during mastectomy and nodal dissection for associated breast carcinoma (nine cases), but may present as a painful or nontender enlarged lymph node (six cases). The latter presentation was almost always associated with a history of injection of liquid silicone or rupture of the prosthesis. All or some of the following findings were present in an affected lymph node: coarse vacuoles, fine vacuoles, and multinucleated giant cells. All lymph nodes contained a variable amount of an unstained, nonbirefringent, refractile material that, in seven of our cases, was shown to contain elemental silicon by energy-dispersive x-ray elemental analysis. In 312 lymph nodes collected from 18 routine cases of breast carcinoma, coarse vacuoles probably representing fat were found in 107 lymph nodes (34%); focal fine vacuoles were found in one (0.3%), and a single multinucleated giant cell was found in one (0.3%). In conclusion, SL probably will be encountered more frequently when cancer-prone age is reached by the susceptible population. In most cases, it is an incidental finding of no clinical significance. However, the histologic diagnosis can be made by observing characteristic light-microscopic changes, which may be supplemented in doubtful cases by energy-dispersive x-ray analysis.

Breast↗
PubMed1999

An investigation of stress and pain perception during manual therapy in asymptomatic subjects.

Stress perceived by the patient during the application of a manual therapy treatment technique may account for the reported findings of sympathoexcitation and hypoalgesia immediately after its application. This study investigated whether there was a difference in the level of perceived stress and pain before, during and after the application of a treatment condition (treatment, placebo or control technique), or whether the difference related to the time course of subject involvement in the study.Twenty-four asymptomatic subjects participated in a double-blind, placebo-controlled, within-subjects study in which stress was measured with a stress rating scale and a stress visual analogue scale. Pain experienced by the subject during the application of the treatment technique was measured with a visual analogue scale and modified McGill pain questionnaire. There was no effect of the treatment condition on perceived stress, but there was a reduction in stress levels over the time course of involvement in the experiment, as demonstrated by pre-application levels of stress. Pain was not produced by the treatment technique.This study demonstrated that stress and pain were not features of the lateral glide manipulation of the cervical spine in asymptomatic subjects. If the dorsal periaqueductal grey region is responsible for the initial effects of manual therapy, as has been previously suggested, then stress and pain do not appear to play a role in activating this system during the application of a manual therapy treatment technique in asymptomatic subjects. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed2001

Childhood cancer and parental use of tobacco: findings from the inter-regional epidemiological study of childhood cancer (IRESCC).

Parental smoking data have been re-abstracted from the interview records of the Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) to test further the hypothesis that paternal cigarette smoking is a risk factor for the generality of childhood cancer. Reported cigarette smoking habits for the parents of 555 children diagnosed with cancer in the period 1980-1983 were compared, in two separate matched pairs analyses, with similar information for the parents of 555 children selected from GP lists (GP controls) and for the parents of 555 hospitalized children (hospital controls). When cases were compared with GP controls there was a statistically significant positive trend (P = 0.02) between the risk of childhood cancer and paternal daily consumption of cigarettes before the pregnancy; there was no significant trend for maternal smoking habit. When cases were compared with hospital controls there was a statistically significant negative trend (P< 0.001) between the risk of childhood cancer and maternal daily consumption of cigarettes before the pregnancy; there was no significant trend for paternal smoking habit. Neither of the significant trends could be explained by adjustment for socioeconomic grouping, ethnic origin or parental age at the birth of the child, or by simultaneous analysis of parental smoking habits. Relations between maternal consumption of cigarettes and birth weights suggested that (maternal) smoking data were equally reliable for case and control subjects, although comparisons with national data suggested that the hospital control parents were unusually heavy smokers. These findings give some support for the hypothesis that paternal cigarette smoking is a potential risk factor for the generality of childhood cancers.

Adult↗
PubMed2000

Treatments for snoring: a comparison of somnoplasty and an oral appliance.

OBJECTIVES: Objectives of the study are 1) to test the effectiveness of somnoplasty (radiofrequency volumetric tissue reduction of the soft palate) for the control of loud, socially disruptive, snoring; 2) to test the long-term efficacy of this treatment by spouse report; and 3) to compare the effectiveness of somnoplasty with another treatment. STUDY DESIGN: Twenty patients with complaints of loud snoring and a respiratory disturbance index no greater than 15 respiratory events per hour with sleep-related episodes of oxygen desaturation no lower than 80% were offered an experimental treatment. Ten were treated with somnoplasty, and a comparison group of 10 matched patients used an oral appliance. All were restudied in the laboratory wearing a device programmed to count minutes of sleep during which snoring was loud, soft, or absent. METHODS: For the 10 somnoplasty patients, a spouse rating of snoring determined whether the patient received one or more treatments. Five patients had a single treatment to three sites, and five others had two such treatments. Ten patients wore an oral appliance of the tongue-retaining type (Snore X, Fremont, CA). RESULTS: Seven of the 10 somnoplasty patients met the improvement criteria set for reduced loud snoring (a spouse rating of 3 or less on a 10-point scale, and 10% or less of sleep time in loud snoring in the laboratory). The comparison group also had a significant improvement in the percentage of sleep time in loud snoring while wearing the Snore X appliance. CONCLUSION: Since there was no significant difference between the two groups in percentage of sleep time spent in loud snoring while treated, the choice of method to control snoring must be based on factors other than efficacy.

Humans↗
PubMed2003

Comparison of laparoscopic versus open partial nephrectomy in a pediatric series.

PURPOSE: Recent advances in laparoscopic surgery as well as increasing experience with these techniques have led to the selection of laparoscopic surgery for many urological procedures. A lesser number of pediatric laparoscopic surgical studies have been reported. Few pediatric comparative laparoscopic versus open surgical procedure studies have been published. We compared 2 groups of similar pediatric patients who underwent partial nephrectomy via the laparoscopic or open technique. MATERIALS AND METHODS: A total of 22 consecutive partial nephrectomies were performed in pediatric patients 3 months to 15 years old. Of these procedures 11 chosen according to surgeon preference were performed laparoscopically and 11 were done by the open technique. Clinical data were obtained by chart review and compared retrospectively in the 2 groups. Demographic data, operative time and blood loss, the perioperative complication rate, hospital stay and costs, postoperative analgesic use and followup findings were compared. RESULTS: Mean operative time in the laparoscopic and open groups was 200.4 and 113.5 minutes, respectively (p <0.0005). Blood loss was less than 50 cc in all patients. In the laparoscopic and open groups mean hospital stay was 25.5 and 32.6 hours (p = 0.068), and mean cost was $6,125 and $4,244 (p = 0.016), respectively. Patients in the laparoscopic group required fewer doses of analgesics than those who underwent open surgery (mean 10.9 versus 21, p = 0.041). CONCLUSIONS: Our findings show that increased operative time and costs are disadvantages of pediatric laparoscopic nephrectomy compared with open techniques. Conversely decreased hospital stay, lower analgesic requirements and cosmesis support the use of laparoscopy for pediatric partial nephrectomy. These differences must be considered when deciding which technique is best for overall patient care.

Adolescent↗
PubMed2007

Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients.

PURPOSE: To report the results of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil/leucovorin (FU/LV) as adjuvant therapy for stage III colon cancer. PATIENTS AND METHODS: Patients with stage III colon carcinoma were randomly assigned to receive either XELOX (intravenous oxaliplatin plus oral capecitabine; 3-week cycle for eight cycles) or standard intravenous bolus FU/LV administered as the Mayo Clinic (Mayo; Rochester, MN) or Roswell Park (RP; Buffalo, NY) regimen for a similar length of time. A total of 1,886 patients were randomly assigned. RESULTS: The safety population comprised 1,864 patients, of whom 938 received XELOX and 926 received FU/LV. Most treatment-related adverse events (AEs) occurred at similar rates in both treatment arms. However, patients receiving XELOX experienced less all-grade diarrhea, alopecia, and more neurosensory toxicity, vomiting, and hand-foot syndrome than those patients receiving FU/LV. Compared with Mayo, XELOX showed fewer grade 3/4 hematologic AE and more grade 3/4 gastrointestinal AE. Compared with RP, XELOX showed less grade 3/4 gastrointestinal AE and more grade 3/4 hematologic AE. As expected grade 3/4 neurosensory toxicity and grade 3 hand-foot syndrome were higher with XELOX. Treatment-related mortality within 28 days from the last study dose was 0.6% in the XELOX group and 0.6% in the FU/LV group. CONCLUSION: XELOX has a manageable tolerability profile in the adjuvant setting. Efficacy data will be available within the next 24 months.

Adult↗
PubMed1997

Progressive supranuclear palsy affects both the substantia nigra pars compacta and reticulata.

We have analyzed the neuropathology of the substantia nigra in four cases of progressive supranuclear palsy compared with age-matched controls and patients with Parkinson's disease. Although there are many reports of severe dopaminergic cell loss in progressive supranuclear palsy, the fate of the GABAergic pars reticulata neurones remains unclear. Serial section analysis and fractional counts of pars compacta neurones (identified by their neuromelanin pigment) and pars reticulata neurones (identified using parvalbumin immunohistochemistry) were performed, and the type and distribution of neuropathology were described. Severe neurodegeneration within the dopaminergic pars compacta was seen in all cases of progressive supranuclear palsy and all cases of Parkinson's disease compared with controls. Lewy body pathology was found only in cases of Parkinson's disease, while neurofibrillary tangles were seen only in cases of progressive supranuclear palsy. Tau-positive astrocytes and neuropil threads were occasionally seen in controls and cases of Parkinson's disease (particularly those of advanced age) but were extremely numerous in all cases of progressive supranuclear palsy. There was a similar decrease in parvalbumin immunoreactivity within the pars reticulata in both progressive supranuclear palsy and Parkinson's disease. However, there was a striking 70% reduction in the number of pars reticulata neurones in progressive supranuclear palsy, with no cell loss observed in Parkinson's disease compared with controls. Our results show that both the dopaminergic pars compacta and the GABAergic pars reticulata are significantly damaged in cases of progressive supranuclear palsy. The distribution of neurodegeneration in patients with Parkinson's disease and progressive supranuclear palsy is discussed with respect to the current theories on pathophysiology in basal ganglia circuitry.

Aged↗
PubMed1992

Calcium oxalate in breast lesions biopsied for calcification detected in screening mammography: incidence and clinical significance.

Two types of calcification have been reported in breast tissue: one appears as dark-blue deposits in routine histologic tissue sections and has been found to be composed mostly of calcium phosphate (CaP); the other is colorless and represents calcium oxalate (CaOx). CaP has been well characterized, but little is known about CaOx. The presence of CaOx was evaluated in 91 breast lesions (71 retrospective and 20 prospective cases) biopsied for the presence of calcification in screening mammography. CaOx was found in 36 cases (39%). CaOx is usually not clearly visible in routine histologic sections. CaOx is found as refractile, strongly birefringent crystals with characteristic morphology. CaOx was present only within benign lesions which frequently showed apocrine metaplasia. However, the breast tissue away from the areas with CaOx displayed a morphologic spectrum roughly similar to that in cases with CaP only. CaOx was clinically significant, i.e., actually represented the mammographic calcification, for which the biopsy was performed in 12% (11/91) of all cases studied and in 31% (11/36) of cases in which CaOx was found. In the cases where CaOx was not considered clinically significant, it was either not radiographically visible or, if visible, did not definitely represent the mammographic calcification for which the biopsy was performed. Since CaOx in breast biopsies is often clinically significant, and since CaOx is not clearly visible in routine sections, examination under polarized light is suggested for all breast biopsies removed for mammographic calcification, particularly when CaP deposits corresponding to the mammographic calcification are not apparent.

Adult↗
PubMed1998

Surgery versus observation for managing obstructive grade 3 to 4 unilateral hydronephrosis: a report from the Society for Fetal Urology.

PURPOSE: The Society for Fetal Urology has undertaken the first multicenter prospective randomized study of high grade obstructive unilateral hydronephrosis to evaluate the natural history of untreated obstruction and compare it to the benefits of pyeloplasty. MATERIALS AND METHODS: Since 1991, infants with isolated unilateral Society for Fetal Urology grade 3 hydronephrosis and ipsilateral obstruction with greater than 40% differential renal function on well tempered renography were studied. Patients were randomly assigned to observation or pyeloplasty groups. Renal ultrasound and well tempered renography were performed biannually for 1 year and yearly thereafter. Crossover criteria for surgery included concurrent worsening of isotope washout and increasing grade of hydronephrosis or a greater than 10% point loss in percent differential renal function that was noted between studies. The end point of the study was the 3-year anniversary of randomization. RESULTS: A total of 32 infants from 10 centers were randomized equally to 2 groups. The starting grade of hydronephrosis and percent differential renal function were similar between the 2 groups. At 6 months and 1 year the grade of hydronephrosis was significantly reduced (p < 0.02) and well tempered renography was significantly more likely to demonstrate no obstruction (p < 0.03) in the surgical group compared with the observation group. The mean percent differential renal function remained stable and similar in both groups. Reduced hydronephrosis and resolution of obstruction in the surgery group persisted as a trend at the 2 and 3-year anniversaries. In the observation group 4 patients (25%) showed enough renal deterioration to qualify for crossover to surgery. CONCLUSIONS: Infant pyeloplasty significantly improved the grade of hydronephrosis and drainage pattern at 6 months and 1 year postoperatively, when compared with observation. Renal function stabilization was similar for either management approach. However, 25% of the patients satisfied objective criteria of status deterioration requiring pyeloplasty.

Cross-Over Studies↗
PubMed2000

Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging.

OBJECTIVE: Cytoarchitectonic changes in the anterior cingulate cortex, hippocampus, subiculum, entorhinal cortex, amygdala, mammillary bodies, and septum were reported in a postmortem study of autism. Previously, the authors found smaller cingulate volume and decreased metabolism of the cingulate in seven autistic patients. In this study, they measured the volume and glucose metabolism of the amygdala, hippocampus, and cingulate gyrus in an expanded group of 17 patients with autism spectrum disorders (autism [N=10] or Asperger's disorder [N=7]) and 17 age- and sex-matched healthy volunteers. METHOD: Subjects performed a serial verbal learning test during (18)F-deoxyglucose uptake. The amygdala, hippocampus, and cingulate gyrus were outlined on magnetic resonance imaging scans, volumes of the structures were applied to matching coregistered positron emission tomography scans, and three-dimensional significance probability mapping was performed. RESULTS: Significant metabolic reductions in both the anterior and posterior cingulate gyri were visualized in the patients with autism spectrum disorders. Both Asperger's and autism patients had relative glucose hypometabolism in the anterior and posterior cingulate as confirmed by analysis of variance; regional differences were also found with three-dimensional significance probability mapping. No group differences were found in either the metabolism or the volume of the amygdala or the hippocampus. However, patients with autism spectrum disorders showed reduced volume of the right anterior cingulate gyrus, specifically in Brodmann's area 24'. CONCLUSIONS: Compared with age- and sex-matched healthy volunteers, patients with autism spectrum disorders showed significantly decreased metabolism in both the anterior and posterior cingulate gyri.

Adult↗
PubMed2006

Effect and duration of lung volume reduction surgery: mid-term results of the Brompton trial.

UNLABELLED: Although many studies have reported improvement in lung function following LVRS, the magnitude of improvement and subsequent decline has not been evaluated against medical therapy after the second year. METHODS: Existing pulmonary function records were collapsed for ech participant since randomisation from Brompton LVRS trial cohort. Longitudinal data analysis was used to profile th history of medically treated patients and the effect of LVRS. RESULTS: Pulmonary function results were collated from survivors over a median of 25 (17 to 39) months. The estimated immediate increase in mean FEV1, following surgery was +0.2591 (0.179, 0.339), with a rate of change of -0.0051 (-0.009, -0.001) per month compared to medical therapy (p < 0.001). The changes in the secondary outcome measures (LVRS compared to medical therapy) were an increase in FVC (p = 0.004), decrease in RV (p < 0.001) and TLC (p < 0.001), with differences that were maintained over time. The initial reduction in RV/TLC ration was sustained (p < 0.001), but the estimated initial increase in peak flow was accompanied by a gradual decline that was not statistically significant (p = 0.062). KCOc showed no immediate change, but there was a gradual sustained increase with time (p = 0.009). Mean oxygen saturations improved and continued to do so compared to patients on medical therapy (p = 0.001). CONCLUSIONS: The immediate increase in FEV1 is not sustained, although the mechanical improvements of LVRS on increasing FVC, reducing both the RV and RV/TLC ratio, appear to be maintained. The important benefits of LVRS may be the gradual and sustained increase in transfer factor accompanied by improved oxygen saturations.

Female↗
PubMed2006

Pediatric renal cell carcinoma: single institution 25-year case series and initial experience with partial nephrectomy.

PURPOSE: RCC represents less than 2% to 6% of pediatric renal tumors. Few reports of long-term outcomes exist. We sought to determine the presentation, treatment and outcome of patients at our institution. MATERIALS AND METHODS: We retrospectively reviewed the age, mode of presentation, mode of treatment, histological subtype, tumor grade, stage and survival of all patients with RCC from 1980 to 2005. RESULTS: A total of 15 patients were identified. Mean age at presentation was 7.9 years. Symptomatic presentations in nearly 75% of patients included gross hematuria, abdominal pain and polycythemia. The remaining 25% of cases were asymptomatic, and were identified by physical examination or incidentally on imaging. Surgical resection consisted of radical nephrectomy in 10 patients and partial nephrectomy in 5. Pathological analysis revealed papillary RCC in 8 patients and clear cell RCC in 7. Six patients had high stage disease. One patient with stage IV disease died 8 months postoperatively. The remaining 14 patients were alive at a mean followup of 4.9 years. All but 1 patient remain recurrence-free, including all of those who underwent nephron sparing surgery. CONCLUSIONS: To our knowledge this single institution series is the first to include children treated with partial nephrectomy. Pediatric patients with RCC tend to be older and more likely to present symptomatically compared to the typical patient with Wilms tumor. Hematuria and abdominal pain were the most common presentations, and papillary RCC was proportionately more common in this series. Our initial experience suggests that equivalent cure rates can be expected from a nephron sparing approach in appropriately selected cases.

Adolescent↗
PubMed1997

Intraluminal crystalloids in breast carcinoma. Immunohistochemical, ultrastructural, and energy-dispersive x-ray element analysis in four cases.

OBJECTIVE: Intraluminal crystalloids have been described in the prostate, salivary gland, and ovary, but have not yet been reported in the breast. We report four cases of breast carcinoma in which these crystalloids were found in ducts with intraductal carcinoma or atypical hyperplasia. The presence of intraluminal crystalloids may be a useful adjunct in making a diagnosis of carcinoma or may be a feature to look for as a marker for the presence of carcinoma. DESIGN: Four cases of breast carcinoma containing intraluminal crystalloids were identified among 6900 surgical breast specimens between January 1990 and June 1995 at M. D. Anderson Cancer Center, Houston, Tex. Those sections with crystalloids identified by hematoxylin-eosin stain were stained with periodic acid-Schiff, Alcian blue, and mucicarmine stains. Immunohistochemical and ultrastructural studies and energy-dispersive x-ray analysis were also performed on these sections. RESULTS: The intraluminal crystalloids were eosinophilic, varied in shape and size, and did not exhibit birefringence under polarized light. Immunohistochemically, the crystalloids were negative for keratin, muscle-specific actin, and kappa and lambda light chains, but the surfaces stained positively for epithelial membrane antigen. By electron microscopy, the crystalloids had no limiting membrane and were composed of an electron-dense material with no discernible periodicity. By energy-dispersive x-ray element analysis, the crystalloids had no mineral content; however, sulfur was found, indicating a protein content. CONCLUSIONS: The pathogenesis and constituents of these intraluminal crystalloids remain to be determined. Inasmuch as intraluminal crystalloids have not been found in normal ducts or acini, or in ductal hyperplasia without atypia, their presence may serve as a marker for breast carcinoma.

Adult↗
PubMed1996

Isolation, car ownership, and small area variation in incidence of acute lymphoblastic leukaemia in children.

To determine whether increased rates of childhood acute lymphoblastic leukaemia (ALL) which had been reported in isolated areas could be attributed to higher proportions of households owning cars, ecological analysis was performed with electoral wards as area units. Previous data were re-analysed using the proportion of households having no car, taken from the 1981 census of England and Wales, as an additional explanatory factor. A specialist registry of haematopoietic malignancies covering one-third of England and Wales (3270 electoral wards) recorded 438 cases of ALL in children diagnosed 1984-89, including 304 in the childhood peak (at ages 1-7 years). Relative risks were derived by Poisson regression of total childhood ALL and at ages 1-7 years for groups of electoral wards classified by isolation and car ownership. Multivariable analyses included adjustment for socio-economic status. No evidence of increased risk of childhood ALL in areas where more households own cars was found. ALL at ages 1-7 years was inversely associated with car ownership (risk in wards with least cars relative to those with most cars = 2.28, 95% CI: 1.12-4.64). The associations with geographic isolation persisted after allowing for car ownership (risks for ALL in young children in isolated relative to built-up areas = 2.19, 95% CI: 1.44-3.33). Levels of car ownership cannot explain the increased rates of childhood ALL which have been observed in isolated areas. No support has been found for a hypothesis relating these excesses to benzene exposure of children transported in cars. The previous explanation for the small area variation of childhood ALL in terms of geographical isolation and interpretation in terms of exposure to common infections continues to be justified.

Adolescent↗
PubMed1996

Increased frequency of HLA-DPB1*0301 in Hodgkin's disease suggests that susceptibility is HVR-sequence and subtype-associated.

Hodgkin's disease (HD) is a complex lymphoma-like disease which occurs as four main subtypes, nodular sclerosing (NS), mixed cellularity (MC), lymphocyte predominant (LP) and lymphocyte depleted (LD). Suggestions from epidemiological studies that HD may represent an unusual response to infection imply that the lack of previous response could be due to genetic factors. Following recent reports suggesting that there is an increased frequency of HLA-DPB1*0301 in Hodgkins disease, we have studied DPB1 in two series of patients using molecular typing methods. One series is a retrospective group of 118 patients over the age of 15 years from a single centre, and the other is a multi-centre prospective group of 45 patients between the age of 16 and 24 years. In both series, the percentage of HD patients with DPB1*0301 is greater than in the controls, confirming that this seems to be an HD-susceptibility allele. However, extension of the analysis in relation to HD subtype shows that the increase in *0301 is present in nodular sclerosing (NS), mixed cellularity (MC) and lymphocyte predominant patients (LP) HD patients, but preliminary evidence suggests an increase in *0401, and possibly *0501 in MC- and LP-HD. The DPB1 hypervariable region (HVR) amino-acid motif Asp55, Glu56 (*0301-like, HVR-C) is increased in NS compared with non-NS (ie MC+LP), whereas the frequency of Ala55, Ala56 (*0401-like) is increased in non-NS compared with NS. Conversely, Asp84, Glu85Ala86(*0301-like, HVR-F) motif is more frequent in NS than non-NS patients, but there is no increase in Gly84, Gly855, Pro86 (*0401-like). These findings suggest that genetic susceptibility in HD may reside at the level of HVR-encoded DPB1 peptide-binding residues, rather than with a specific allele, and that this may in some way influence the HD subtype.

Adolescent↗