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Biomedical subjects

R Stone

Publications and source records attributed to R Stone.

At least 73 records · Page 4Linked to original sources
PubMed1997

CD6-depleted allogeneic bone marrow transplantation for acute leukemia in first complete remission.

The appropriate timing of bone marrow transplantation (BMT) for adults with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) is controversial. Although allogeneic transplantation results in a lower risk of disease recurrence than intensive chemotherapy alone, overall outcome following BMT may not be improved due to the higher incidence of therapy-related fatal complications, frequently as a result of the development of graft-versus-host disease (GVHD). Selective T-cell depletion of donor marrow can reduce the incidence of GVHD and thereby limit transplant-related toxicity. Herein we report the risk of GVHD, incidence of transplant related mortality (TRM), likelihood of disease relapse, and overall survival in adult patients undergoing BMT with CD6 depleted allogeneic marrow for acute leukemia in first remission. Forty-one consecutive allogeneic transplants were performed on patients with acute leukemia and high-risk features (28 AML, 13 ALL) using T12 monoclonal antibody and complement to remove CD6+ T cells from donor marrow. No pre- or posttransplant immune suppressive medications for GVHD prophylaxis were administered. The actuarial estimated risk of grade 2 to 4 acute GVHD was 15% in patients receiving HLA identical grafts. Chronic GVHD developed in five patients. The estimated risk of TRM for patients in first complete remission was 5% at Day +100 and 16% at 2 years. Fatalities attributable to infection with cytomegalovirus or Epstein-Barr virus occurred in only three patients. Estimated probabilities of relapse, overall survival, and event-free survival at 4 years were 25%, 71%, and 63%, respectively. No significant differences in GVHD, TRM, relapse rate, or survival was observed for patients with AML compared with those with ALL. Allogeneic transplantation with CD6 depleted bone marrow is effective in consolidating remissions of high-risk patients with acute leukemia in first remission without excessive toxicity.

Acute Disease↗
PubMed1997

Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III.

Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination of this gene reveals loss-of-function mutations that impair renal chloride reabsorption in the thick ascending limb of Henle's loop. Mutations in seventeen kindreds have been identified, and they include large deletions and nonsense and missense mutations. Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA. Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper- or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent. These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents.

Bartter Syndrome↗
PubMed1997

MIST VR. A laparoscopic surgery procedures trainer and evaluator.

The key bimanual instrument tasks involved in laparoscopic surgery have been abstracted for use in a virtual reality surgical skills evaluator and trainer. The trainer uses two laparoscopic instruments mounted on a frame with position sensors which provide instrument movement data that is translated into interactive real time graphics on a PC (P133, 16 Mb RAM, graphics acceleration card). An accurately scaled operating volume of 10 cm3 is represented by a 3D cube on the computer screen. "Camera" position and size of target objects can be varied for different skill levels. Targets appear randomly within the operating volume according to the skill task and can be grasped and manipulated with the instruments. Accuracy and errors during the tasks and time to completion are logged. Mist VR has tutorial, training, examination, analysis and configuration modes. Six tasks have been selected and include combinations of instrument approach, target acquisition, target manipulation and placement, transfer between instruments, target contact with optional diathermy, and controlled instrument withdrawal/replacement. Tasks can be configured for varying degrees of difficulty and the configurations saved to a library for reuse. Specific task configurations can be assigned to individual students. In the examination mode the supervisor can select the tasks, repetitions and order and save to a specific file for that trainee. Progress can be assessed and there is the option for playback of the training session or examination. Data analyses permit overall, including task, and right or left hand performances to be quantified. Mist VR represents a significant advance over the subjective assessment of training performances with existing "plastic box" basic trainers.

Computer-Assisted Instruction↗
PubMed1997

Loss of bactericidal activity from contact lens storage solutions.

PURPOSE: The purpose of this study was to evaluate the effect of lens storage on the bactericidal activities of disinfecting solutions. METHODS: HYDROCURVEII (55% water content) soft contact lenses were soaked in OPTI-FREE Rinsing, Disinfecting, and Storage Solution (preserved with polyquaternium-1 [PQ-1]) or ReNu Multi-Purpose Solution (polyaminopropyl biguanide [PHMB]). After the lenses were removed, solutions were challenged with Pseudomonas aeruginosa and Staphylococcus aureus. Uptake of the antimicrobial agents by the lenses was evaluated by placing the lenses on plates seeded with S. aureus and observing for zones of growth inhibition. RESULTS: The bactericidal activity of the PHMB preserved solution decreased after 4 hours of storage time and showed no activity after storage for 3 days. Lenses soaked in the PHMB preserved solution produced zones of inhibition. The results suggest that the PHMB in the solution accumulates in the lens. This decreases the levels of preservative in the solution that is no longer available during lens storage. Neither decrease in bactericidal activity nor accumulation of the PQ-1 preservative in the lens occurred during storage with the PQ-1 solution. CONCLUSION: These results demonstrate that PQ-1 preserved solutions maintain bactericidal activity overnight and during prolonged storage without detectable uptake by lenses.

Biguanides↗
PubMed1996

Trials of 9-amino-20(S)-camptothecin in Boston.

9-Amino-20(S)-camptothecin (9-AC) is an analog of camptothecin with limited water solubility which has shown significant preclinical activity in a variety of human solid tumor xenografts. A Phase I trial using a soluble formulation of 9-AC, given as a 72-hour continuous infusion, has been completed. Thirty-one patients with resistant cancers received 5-60 micrograms/M2/h at three week intervals. The Maximum Tolerated Dose (MTD) was 45 micrograms/M2/hour. Neutropenia was the dose limiting toxicity, with few significant non-myelosuppressive toxicities. Minor responses were seen in 3/31 patients. Pharmacokinetic studies of 9-AC lactone (closed ring) showed substantial interpatient variability with a predicted half-life of 36 hours. A phase I/II trial of the same formulation of 9-AC is ongoing in refractory leukemia. Stomatitis and diarrhea are the non-myelosuppressive dose limiting toxicities. Evidence of antineoplastic activity has been seen in 3/15 patients. A Phase II trial in previously untreated metastatic breast cancer is also underway. A Phase I trial of a colloidal dispersion formulation, not yet completed, is better tolerated with a MTD > 45 micrograms/M2/h as a 72-hour continuous infusion. Evidence of antineoplastic activity has also been demonstrated.

Adult↗
PubMed1996

Differential expression of cell adhesion molecules on trigeminal cutaneous and muscle afferents.

Previous work from our laboratory (Woodbury and Scott, 1995) suggested that embryonic cutaneous and muscle afferents might express different surface cell adhesion molecules (CAMs) on their growth cones. To examine this possibility directly we measured the relative levels of expression of various adhesion molecules on growth cones of neurons from the dorsomedial portion of the trigeminal ganglion (DM-TG), which are largely cutaneous, and from the trigeminal mesencephalic nucleus (TMN), which are exclusively muscle afferents. Axonin-1,L1, BEN, and N-cadherin were expressed more abundantly on DM-TG growth cones, whereas N-CAM was more abundant on TMN neurons. Expression of polysialated N-CAM was similar on the two populations, addition of NGF and NT-3 appeared to increase expression of polysialated N-CAM on TMN neurons. Although the levels of L1 and axonin-1, both of which bind L1, were markedly different on TMN and DM-TG neurons, these differences were not sufficient to cause dramatic differences in the growth rates of TMN and DM-TG neurons on L1.

Animals↗
PubMed1996

Fertility rates among lead workers and professional bus drivers: a comparative study.

We examined the relationship between lead exposure and fertility among men in a retrospective cohort study. Fertility (1981-1992) of lead-exposed workers was determined from birth certificate information and was compared with that of nonexposed workers. The exposed group consisted of 4256 reproductive-age male workers reported to the New York State Heavy Metals Registry. The comparison group consisted of a random sample of male bus drivers licensed in the state of New York; these men were frequency-matched by age and residence to the men who were exposed to lead. The actual number of births among lead workers was lower than the expected number of births for that group (standardized fertility ratio [SFR] = 0.88; 95% confidence interval [CI] = 0.81-0.95), especially among those who had elevated blood lead levels for longer than 5 years (SFR = 0.43; 95% confidence interval [CI]: = 0.31, 0.59). Even after adjusting for age, race, education, and residence, workers with > 5 years of exposure had reduced likelihood of fathering a child than those with a shorter period of exposure (relative risk, 0.38; 95% CI: 0.23, 0.61). Our study indicates that men with a long duration of lead exposure might have reduced fertility.

Adult↗
PubMed1996

Molecular IDDM epidemiology: international studies. WHO DiaMond Molecular Epidemiology Sub-Project Group.

The WHO DiaMond Molecular Epidemiology Sub-Project is testing the hypothesis that the geographic differences in IDDM incidence reflect population variation in the frequency of IDDM susceptibility genes (i.e., DQA1 and DQB1 alleles with sequences coding for arginine (R) in position 52 of the DQ alpha-chain, and an amino acid other than aspartic acid (ND) in position 57 of the DQ beta-chain, respectively) using a standardized case-control design. Data from twelve populations which have completed (or have nearly completed) recruitment and HLA molecular analyses are presented. There was an approximate 2-fold increase in the frequencies of DGA1*0301, DQB1*0201 and DQB11*0302 among IDDM cases compared to non-diabetic controls in most populations. Interestingly, DQA*0301 was more common in low versus moderate-high incidence countries. DQB1*0201 and DQB1*0302 were more prevalent in the moderate-high incidence areas. DQA1*R and DQB1*ND were both consistent markers of IDDM risk, with stronger associations in moderate-high versus low incidence areas. In general, individuals homozygous for both DQA1*R and DQB1*ND had the highest genotype-specific IDDM incidence rates, which approximated risk estimates for first degree relatives in several countries. These data revealed considerable variation in the frequencies of DQB1 and DQA1 alleles across countries, which likely contribute to the global patterns of IDDM incidence.

Alleles↗
PubMed1996

Primary care diagnosis of acute abdominal pain.

The abdomen, as the largest cavity in the body, holds both fixed as well as relatively mobile organs, which when either diseased, traumatized, malfunctioning, or infected may present a wide and diverse range of signs and symptoms. Clues to the origin of abdominal pain can be well-localized or referred and quite obtuse. This article reviews the surface anatomy of the abdomen, the types of abdominal pain, approach to the patient with abdominal pain, and history-taking and physical examination. Adjunctive studies, which might help to reduce the differential diagnosis, are mentioned. The goal of this article is to help the reader formulate an accurate diagnosis in a timely manner via a complete but also well-focused physical examination; attention is paid to a comprehensive differential diagnosis to include common and not so common causes of acute abdominal pain. Intra-abdominal sources of abdominal pain include: peritonitis, bowel obstruction, and vascular disorders. Extra-abdominal sources of abdominal pain include the thorax, pelvis, and the abdominal wall. Some metabolic and neurogenic sources of abdominal pain are examined. Life-threatening causes of abdominal pain include ectopic pregnancy, acute myocardial infarction, abdominal aortic aneurysm, splenic rupture, and obstructed bowel. Discussion of these entities concentrates on the initial presentation of the patient, typical progression of symptoms, and appropriate initial treatment as well as referral. The process of ruling out emergent abdominal pain is also examined.

Abdomen, Acute↗
PubMed1996

Blood folic acid and vitamin B12 in relation to neural tube defects.

OBJECTIVE: To determine the relation between blood folic acid and serum vitamin B12 in neural tube defect pregnancies using data from the MRC Vitamin Study and a literature review of all studies. DESIGN: Stored blood samples collected as part of a randomised trial of vitamin supplementation in the prevention of neural tube defects were retrieved from affected pregnancies (cases) and unaffected pregnancies (controls). Four controls were matched with each case by centre, maternal age and duration of storage of the blood sample. The samples had been collected from women at entry to the trial, immediately before the women became pregnant, and at around 12 weeks of pregnancy. Our results were combined with those already published from other studies to obtain an overall assessment of blood folic acid and vitamin B12 in relation to neural tube defects. SETTING: Blood samples were collected as part of the MRC Vitamin Study. The collaborating centres were in the United Kingdom, Hungary, Israel, Australia, Canada and Russia. PARTICIPANTS: Twenty-seven women with neural tube defect pregnancies and 108 matched controls with unaffected pregnancies. RESULTS: Serum and red cell folic acid and serum vitamin B12 levels were lower in the cases than in controls at each of the three occasions when blood samples were collected, but no comparison was significant (P > 0.05). A systematic review of all studies from the literature showed that on average, during the 1st trimester of pregnancy, serum folic acid was 0.6 ng/ml lower in neural tube defect pregnancies (P < 0.01), red cell folic acid was 77 ng/ml lower (P < 0.001) and serum vitamin B12 was 38 ng/l lower (P < 0.001). A logistic regression showed no association between serum B12 and neural tube defects after allowing for serum folic acid. CONCLUSION: our results are consistent with other evidence that folic acid and vitamin B12 levels are lower in women with neural tube defect pregnancies and consistent with evidence from randomised trials which showed that folic acid is protective.

Female↗