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Biomedical subjects

J Stone

Publications and source records attributed to J Stone.

At least 37 records · Page 2Linked to original sources

Low frequency of germline E-cadherin mutations in familial and nonfamilial gastric cancer.

Little is known about the relative contributions of genetic and environmental factors to the development of gastric cancer. Mutations in the cell adhesion molecule E-cadherin are recognized to be associated with the development of undifferentiated, diffuse and invasive gastric cancers. A recent study of two gastric cancer families has shown that germline mutations in the E-cadherin gene can be causative (Guilford P et al, Nature 1998; 26: 402-405). We have examined the E-cadherin gene for constitutive mutations in a systematic series of 106 gastric cancer patients, 10 with a family history of the disease and 96 sporadic cases. No pathogenic mutations were observed in any of the 106 patients. The results indicate that germline mutations in E-cadherin will not account for more than 3% of gastric cancers.

Adenocarcinoma

Pregnancy complications and neonatal outcomes in multifetal pregnancies reduced to twins compared with nonreduced twin pregnancies.

Our objective was to compare the pregnancy complications and neonatal outcomes of multifetal pregnancies reduced to twins to those in twin pregnancies without multifetal pregnancy reduction (MPR). A cohort study was performed in patients with dichorionic twin pregnancies who reached 24 weeks' gestation and delivered at the Mount Sinai Medical Center between 1986 and 1997. A study population of 77 multifetal pregnancies reduced to twins were compared with 140 dichorionic twin pregnancies without MPR regarding pregnancy complications and neonatal outcomes. Statistical analysis was performed with Chi-square and two-tailed Student's t-tests. Multifetal pregnancies reduced to twins were similar to nonreduced twins in all parameters studied except the cesarean section rate and neonatal polycythemia. Increased cesarean section rate in MPR group was attributed to elective indications. Pregnancy-induced hypertension was found to be higher only in a subgroup of patients (i.e., 4-2). Multifetal pregnancies reduced to twins do not differ from the twin pregnancies without MPR in the overwhelming majority of pregnancy complications and neonatal outcomes.

Adult

Mycobacterial spindle cell pseudotumor of the brain: a case report and review of the literature.

Spindle cell pseudotumors found in the skin, lymph nodes, bone marrow, spleen, lungs, and retroperitoneum have been reported recently in immunosuppressed patients, including those with acquired immunodeficiency syndrome. The authors report a similar lesion limited to the brain in a 38-year-old human immunodeficiency virus-negative man receiving steroid therapy for treatment of sarcoidosis. Histopathologically the lesions were composed of spindle and epithelioid histiocytes, small foci of necrosis, and numerous acid-fast bacilli. The acid-fast bacilli were determined by culture and polymerase chain reaction to be Mycobacterium avium intracellulare. Because of the uncommon histologic appearance of this lesion and the potential for treatment if recognized, mycobacterial spindle cell pseudotumors should be included in the differential diagnosis of spindle cell lesions in the brain in immunosuppressed patients.

Adult

Open versus arthroscopic ankle arthrodesis: a comparative study.

A retrospective review was undertaken for 36 patients who underwent ankle arthrodesis. Nineteen patients underwent an arthroscopic ankle arthrodesis, and 17 patients underwent an open arthrodesis. Only patients with limited angular deformities were suitable candidates for an arthroscopic arthrodesis. The open arthrodesis group inclusion criteria were defined by the maximum coronal and sagittal plane deformity in the arthroscopic group. Perioperative parameters were compared and analyzed. Arthroscopic ankle arthrodesis yielded comparable fusion rates to open ankle arthrodesis, with significantly less morbidity, shorter operative times, shorter tourniquet times, less blood loss, and shorter hospital stays. Arthroscopic ankle arthrodesis is a valid alternative to traditional open arthrodesis of the ankle for selected patients with ankle arthritis.

Adolescent

Pulmonary manifestations of ulcerative colitis mimicking Wegener's granulomatosis.

We describe 2 patients with quiescent ulcerative colitis who developed clinical syndromes suggesting Wegener's granulomatosis. Both patients had features of systemic illnesses, nodular lung lesions, and antineutrophil cytoplasmic antibodies. Although the inflammatory bowel disease of both patients was quiescent at the time of their pulmonary presentations, lung biopsy results were consistent with pulmonary complications of ulcerative colitis, an unusual manifestation of that disorder. These cases illustrate that pathological confirmation of the diagnosis is essential in cases of suspected vasculitis. The patients' pulmonary lesions resolved promptly after treatment with corticosteroids.

Adult

The impact of basic fibroblast growth factor on photoreceptor function and morphology.

PURPOSE: To assess the impact of basic fibroblast growth factor (bFGF) on photoreceptor function and morphology. METHODS: Impact was assessed in two models. In one, the endogenous expression of bFGF in photoreceptors was raised by sectioning one optic nerve of rats 3 to 4 weeks before study. In the other, bFGF was injected into the vitreous chamber in rats and cats. Retinal function was assessed from the electroretinogram (ERG), and retinal morphology was studied using DNA dyes, immunolabeling, and in situ hybridization. RESULTS: In both models of bFGF upregulation, the ERG b-wave was suppressed over a wide stimulus range and in light- and dark-adapted conditions. The a-wave was not suppressed by either procedure and at the brightest intensities was enhanced by both procedures. In nerve-sectioned eyes, outer retina appeared normal histologically, but levels of bFGF protein in the inner and outer nuclear layers were raised, whereas bFGF mRNA levels remained unchanged. In both models, levels of synaptophysin in the outer plexiform layer and of cytochrome oxidase in inner segments were raised in association with increases in bFGF protein levels. CONCLUSIONS: bFGF increased the ability of photoreceptors to respond to light but attenuated the transmission of this response to inner retinal cells, presumably by blocking the photoreceptor-bipolar synapse. If the expression of bFGF protein is upregulated in human photoreceptor dystrophies, it may contribute a reversible component to the loss of vision. The relationship between these actions of bFGF and its ability to protect photoreceptors from stress remains to be established.

Animals

[Structure of the interrelations between retinal neuroglia and ganglion cells].

Organization of glial environment of bodies and axons of cat retinal ganglion cells (GC) was analysed electron microscopically. Similarities and differences in types of contacts between macroglial cells and GC plasmalemma throughout its length were demonstrated. Regularities of changes of types of glia surrounding different types of GC were established. GC body was surrounded by the processes of Muller gliocytes, while a special glial crown appearing as multiple radial finger-shaped astrocyte processes covers GC initial segment. Possible functional aspects of structural organization of interrelations of GC body and axons with gliocytes are discussed.

Animals

Secondary amyloidosis associated with giant cell arteritis/polymyalgia rheumatica.

Although giant cell arteritis (GCA) is characterized by chronic inflammation, secondary (AA) amyloidosis appears to be an exceptionally rare complication of this disorder. We describe an 84-year-old man with biopsy proven GCA and polymyalgia rheumatica (PMR) who was found at autopsy to have AA amyloid deposition in numerous organs, 9 years after his diagnosis of GCA. Persistent musculoskeletal symptoms, attributed to refractory PMR during the patient's life, were likely due to AA amyloidosis. This unrecognized complication of GCA/PMR confounded his therapy, leading to excessive treatment with corticosteroids and methotrexate. This case shows that the occurrence of AA amyloidosis should be considered in patients with "refractory PMR" developing after a period of treatment, and that autopsies play a vital role in enigmatic cases.

Aged

Takayasu's arteritis involving proximal pulmonary arteries and mimicking thromboembolic disease.

The pulmonary manifestations of Takayasu's arteritis (TA) are frequently overshadowed by the systemic circulation involvement. We describe a patient who presented with life threatening complications of unrecognized proximal pulmonary arterial disease that mimicked thromboembolic disease. We review the literature on pulmonary involvement in TA, and discuss the use of imaging studies in this disease.

Adult

Evidence that the influence of ganglion cell axons on astrocyte morphology is mediated by action spike activity during development.

In many mammal retinas, the morphology of astrocytes is strongly influenced by nearby axons of ganglion cells. Astrocyte processes stretch along the axons, fine extensions of the processes contact node-like specialisation of the axon membrane and the morphology of the adult astrocyte is strongly determined by this relationship. The mechanism which attracts astrocyte processes to contact specific regions of the axon membrane is not known however. This study presents evidence that in the neonatal cat blocking the impulse activity of ganglion cells with the Na+-channel blocker tetrodotoxin (TTX) leads to a loss of the axon-related morphology of astrocytes. The morphological change induced in astrocytes by TTX was greater in younger animals and could not be detected in the adult. Conversely, if the TTX block was maintained for 4 postnatal weeks the changes induced in astrocytes persisted at least to 13 weeks. The TTX-induced loss of axon-related morphology in astrocytes suggests that the signal by which axons attract astrocyte processes to contact the axonal membrane in ways which modify astrocyte morphology is released by action spike activity during development.

Action Potentials

Fluctuations in blood lipid levels during furosemide therapy: a randomized, double-blind, placebo-controlled crossover study.

BACKGROUND: Acute decreases in intravascular volume are associated with increases in lipid levels. Furosemide causes acute changes in intravascular volume during prolonged therapy but is thought to have little effect on lipid levels. METHODS: To determine if there are daily acute rises in lipid and lipoprotein levels associated with changes in intravascular volume during long-term furosemide ingestion therapy, we performed a randomized, double-blind, placebo-controlled crossover study in 10 patients. RESULTS: In the 8 hours after furosemide ingestion there were increases in levels of plasma cholesterol (10.1%; P = .001), high-density lipoprotein cholesterol (9.0%; P = .006), and apolipoprotein B (9.8%; P = .003). The increases in levels of triglycerides (11.5%; P = .17) and apolipoprotein A-1 (13.3%; P = .051) were of similar magnitude but more variable and did not achieve statistical significance. There was no substantial change in the total cholesterol-high-density lipoprotein cholesterol ratio (0.6%; 95% CI,-0.74% to 8.6%; P =.88). CONCLUSION: This study indicates that there are acute increases in lipid levels after furosemide ingestion during prolonged therapy, which could affect the interpretation of lipid levels and cardiovascular risk in patients.

Aged

The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women.

OBJECTIVES: The objectives of this study were to describe the early natural history of human papillomavirus (HPV) infection by examining a cohort of young women positive for an HPV test and to define within this cohort (1) the probability of HPV regression, (2) the risk of having a squamous intraepithelial lesion, and (3) factors that were associated with HPV regression. STUDY DESIGN: The study was a cohort analytic design. An inception cohort of 618 women positive for HPV participated. HPV testing, cytologic evaluation, and colposcopic evaluation were performed at 4-month intervals. HPV testing was characterized for two groups: low risk (five types rarely associated with cancers) and high risk (nine types most commonly associated with cancers). RESULTS: Estimates provided by Kaplan-Meier curves showed that approximately 70% of women were found to have HPV regression by 24 months. Women with low-risk HPV type infections were more likely to show HPV regression than were women with high-risk HPV type infections (log rank test p = 0.002). The relative risk for the development of high-grade squamous intraepithelial lesion (HSIL) was 14.1 (95% confidence interval: 2.3, 84.5) for women with at least three positive tests for high-risk HPV preceding the development of the HSIL compared with that for women with negative tests for high-risk HPV. However, 88% of women with persistent positive HPV tests have not had HSIL to date. No factors associated with high-risk HPV type regression were identified except for a negative association with an incident history of vulvar condyloma (relative risk = 0.5 [95% confidence interval: 0.3 to 0.8]). CONCLUSION: Most young women with a positive HPV test will become negative within a 24-month period. Persistent positive tests with oncogenic HPV types represented a significant risk for the development of HSIL. However, we found that most young women with persistent positive HPV tests did not have cytologically perceptible HSIL over a 2-year period. Factors thought to be associated with the development of HSIL were found not to be important in HPV regression.

Adolescent

An ultrastructural and systemic analysis of glycosaminoglycans in thyroid-associated ophthalmopathy.

PURPOSE: To determine the ultrastructural localisation of glycosaminoglycans (GAGs) in the extraocular muscles (EOMs) of patients with thyroid-associated ophthalmopathy (TAO) and to see whether the quantity and type of GAGs present in blood and urine are markers of the disease. METHODS: Biopsies of affected EOMs were taken and studied by transmission electron microscopy (TEM). These were either fixed conventional for TEM, or in 0.5% tannic acid and others for immunogold staining. Serum hyaluronan (HA) was measured using a radioimmunoassay in patients with TAO as well as control subjects, and urinary GAG levels assessed by photometric quantitation of hexuronic acid after reaction with carbazole. The excretion pattern of the urinary GAGs was determined by discontinuous electrophoresis. RESULTS: TEM showed that there is a marked expansion of the endomysial space in TAO EOM biopsies as compared with non-TAO strabismus specimens. This is caused by an increased number of collagen fibres, interspersed with a granular amorphous material surrounding striated collagen fibres shown to be hyaluronan by immunogold staining. In contrast, serum hyaluronan concentrations were similar in TAO and control patients, although there was a statistically significant difference in the urinary GAG excretion between the two groups of patients examined. By discontinuous electrophoresis, chondroitin sulphate and heparan sulphate were present in both patients and controls. CONCLUSION: GAGs and in particularly HA are present at the EOM level in patients with recently inactive TAO. However, serum levels of HA and urinary GAGs are not sensitive indicators for their presence within the EOMs.

Adult