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Biomedical subjects

J Roy

Publications and source records attributed to J Roy.

At least 91 records · Page 5Linked to original sources
PubMed1996

Granulocyte recovery after sequential transfusion of mobilized blood stem cell concentrates in syngeneic recipients.

Three patients received sequential transfusions of G-CSF-mobilized peripheral blood stem cells from their identical twin in an attempt to abrogate neutropenia. Blood stem cells were harvested by leukapheresis in the healthy donor twins following mobilization with rhG-CSF at 5 micrograms/kg/day subcutaneously for at least 5 days. An average of 2.2 x 10(7) CFU-GM (range: 1.4-3.3) were collected and transfused without further manipulation. One patient, transfused with a CFU-GM dose of 3 x 10(7) on day +6 after a syngeneic marrow transplant, experienced near-complete elimination of absolute neutropenia until spontaneous engraftment occurred on day +11. In the other two patients, we unexpectedly observed a transient granulopoietic inhibition, possibly related to the high T cell content of the blood stem cell transfusions.

Female↗
PubMed1996

[Pancreatic somatostatinoma and MEN 1. Apropos of a case. Review of the literature].

The pancreatic somatostatinoma belongs to the type of rare endocrine tumors of the pancreas. We report the observation of a 54 year old woman. Previously she was suffering from diabetes mellitus. An abdominal ultrasonography revealed an endocrine tumor of the pancreatic tail. There was no specific symptomatology, with the exception for the hyperglycaemia. The diagnosis of somatostatinoma was certified post operatively by the immunocytochemistry of the tumor. Then, the patient developed a hypercalcaemia associated with an increase of parathyroid hormone. The surgery of the neck revealed three hyperplastic parathyroids, inducing this association as a multiple endocrine neoplasia type 1 (MEN 1). The patient did not develop pituitary tumor. Afterwards, scintigraphy with 111 Indium- octreotide showed a residual tumor at the head of pancreas. Basal levels of somatostatine and calcium, pentagastrine test, computed tomography scan, arteriography were negative. The presence of a second somatostatinoma was confirmed by surgery and immunohistology. One year after the surgery, the patient remains clinically well. The pancreatic localization of the somatostatinoma in a MEN 1 is poorly documented. Its malignant nature can only be assured by the presence of metastases. The genetic detection of the MEN 1 becomes possible. Above all, the treatment is based on surgery and/or chemotherapy (Fluoro-Uracile; Streptozotocine). In our case, 111 In-octreotide scintigraphy was the only method demonstrating a residual focus, suggesting it could be an element of reference for the diagnosis and survey of somatostatinoma the watch of patients having a treatment for somatostatinoma.

Diabetes Mellitus, Type 2↗
PubMed1996

Cytokine expression in human cutaneous chronic graft-versus-host disease.

Although chronic graft-versus-host disease (GVHD) remains a frequent complication of bone marrow transplantation (BMT), the pathogenesis remains unclear. We examined the potential role of cytokines in mediating chronic GVHD. Skin samples from seven patients with cutaneous chronic GVHD, six post-BMT controls and six normal controls were evaluated by reverse transcription polymerase chain reaction for the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha), Th1-associated cytokines IL-2 and interferon-gamma (IFN-gamma), Th2-associated cytokines IL-4, IL-5 and IL-10, and fibrosis-associated cytokines platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). IFN-gamma transcription was significantly more frequent in cutaneous chronic GVHD (86%) vs post-BMT and normal controls (17% (P = 0.03) and 0 (P = 0.005), respectively). IL-2 transcription was more frequent in chronic GVHD (28%) and post-BMT controls (50%) vs normal controls (17%). TNF-alpha mRNA was frequent in chronic GVHD (71%) and post-BMT controls (83%), but not significantly more than in normal controls (50%). Transcription of IL-1alpha, IL-4, IL-5 and IL-10 was infrequent in all three groups. PDGF and TGF-beta mRNA were detected in the majority of all samples. The frequent transcription of IFN-gamma in cutaneous chronic GVHD supports its potential role in mediating the associated tissue injury. While the cellular sources of these cytokines are uncertain, their expression and secretion in situ may propagate the cytotoxic cascade and perpetuate the tissue injury. Better understanding of the contribution of FN-gamma and other cytokines to the pathogenesis of chronic GVHD may allow the design of more specific and more effective therapy.

Adult↗
PubMed1995

The tissue expression of cytokines in human acute cutaneous graft-versus-host disease.

Although acute graft-versus-host disease (GVHD) is a common complication after allogeneic bone marrow transplantation (BMT), the specific pathophysiology of tissue damage has not been elucidated. We have previously described an infiltrate of CD2+, CD8+, alpha/beta receptor+ T lymphocytes, and the upregulation of ICAM-1 in tissues with acute GVHD. We hypothesized that these infiltrating lymphocytes may secrete cytokines that could contribute to tissue damage. In the current study, we used reverse transcription (RT) polymerase chain reaction (PCR) to explore the mRNA expression of candidate inflammatory cytokines IL-1 alpha, IL-2, IL-4, IL-6, TNF-alpha, and interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells (PBMC) and skin biopsies of allogeneic BMT patients with GVHD and controls. In post-BMT control PBMC (n = 10); IL-2 RNA was infrequent (20% of samples) but was significantly more frequently detectable (71%; P < 0.05) after development of acute GVHD (n = 7). IL-4 expression was also more common in PBMC from patients with acute GVHD (57% vs. 30%; P < 0.05). Consistent with the PBMC data, IL-2 and IL-4 RNA were also more frequently detectable in skin biopsies with GVHD (n = 10): 70% of samples expressed IL-2 vs. 25% of normal controls (n = 8; P < 0.05); 60% had detectable IL-4 RNA vs. 0% of controls (P < 0.05). IFN-gamma detectability (40% vs. 12%; P < 0.05) was also more frequent in GVH skin. For both PBMC and skin, IL-1 alpha expression was infrequent in GVHD and controls, whereas TNF-alpha and IL-6 were expressed in nearly all samples. These data suggest that upregulated expression of IL-2, IL-4, and IFN-gamma may be part of the inflammatory cascade of human acute GVHD, while IL-1 alpha, TNF-alpha, and IL-6 are not discriminatory for the inflammation observed at the time of initial GVHD diagnosis.

Acute Disease↗
PubMed1995

Dosimetry guidelines to minimize urethral and rectal morbidity following transperineal I-125 prostate brachytherapy.

PURPOSE: To establish dosimetry guidelines to minimize urethral and rectal morbidity following permanent I-125 prostatic brachytherapy. METHODS AND MATERIALS: Dosimetric parameters were correlated with long-term morbidity for 65 patients following transperineal I-125 implantation for Stage T1/T2 prostatic carcinoma. The prescribed minimum prostatic dose was 150 Gy. The median total activity used was 48 mCi (range: 32-77 mCi). Patients were followed for 1-5 years (median follow-up: 2 years). Postimplant computerized tomography (CT)-based dosimetry was performed for 45 patients. Morbidity was evaluated using a modification of the RTOG grading system, with a scale of grade 0-5. RESULTS: The incidence of grades 2 and 3 urinary morbidity was associated with the maximum central urethral dose (p = 0.03), and with the length of urethra that received greater than 400 Gy (p = 0.07). Patients with larger prostates had more long-term urinary morbidity (p = 0.06). Rectal bleeding (RTOG grade 1) or ulceration (RTOG grade 2) was associated with irradiation of the rectal wall to doses in excess of 100 Gy (p = 0.02). There was no relationship between the matched peripheral dose (MPD), mCi/source or total mCi implanted and long-term morbidity. CONCLUSIONS: Postimplant, CT-based dosimetry can predict which patients are at higher risk of radiation-related morbidity. More simplistic parameters including the MPD, total activity implanted, or mCi/source, had no relationship with morbidity. To decrease the risk of long-term morbidity, an effort should be made to keep the central urethral dose below 400 Gy, and the rectal surface dose below 100 Gy.

Brachytherapy↗
PubMed1995

Structurally related but functionally distinct yeast Sm D core small nuclear ribonucleoprotein particle proteins.

Spliceosome assembly during pre-mRNA splicing requires the correct positioning of the U1, U2, U4/U6, and U5 small nuclear ribonucleoprotein particles (snRNPs) on the precursor mRNA. The structure and integrity of these snRNPs are maintained in part by the association of the snRNAs with core snRNP (Sm) proteins. The Sm proteins also play a pivotal role in metazoan snRNP biogenesis. We have characterized a Saccharomyces cerevisiae gene, SMD3, that encodes the core snRNP protein Smd3. The Smd3 protein is required for pre-mRNA splicing in vivo. Depletion of this protein from yeast cells affects the levels of U snRNAs and their cap modification, indicating that Smd3 is required for snRNP biogenesis. Smd3 is structurally and functionally distinct from the previously described yeast core polypeptide Smd1. Although Smd3 and Smd1 are both associated with the spliceosomal snRNPs, overexpression of one cannot compensate for the loss of the other. Thus, these two proteins have distinct functions. A pool of Smd3 exists in the yeast cytoplasm. This is consistent with the possibility that snRNP assembly in S. cerevisiae, as in metazoans, is initiated in the cytoplasm from a pool of RNA-free core snRNP protein complexes.

Amino Acid Sequence↗
PubMed1995

Proscar: five-year experience.

We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH.

Aged↗
PubMed1995

The final stages of spliceosome maturation require Spp2p that can interact with the DEAH box protein Prp2p and promote step 1 of splicing.

Pre-mRNA processing occurs by assembly of splicing factors on the substrate to form the spliceosome followed by two consecutive RNA cleavage-ligation reactions. The Prp2 protein hydrolyzes ATP and is required for the first reaction (Yean SL, Lin RJ, 1991, Mol Cell Biol 11:5571-5577; Kim SH, Smith J, Claude A, Lin RJ, 1992, EMBO J 11:2319-2326). The Saccharomyces cerevisiae SPP2 gene was previously identified as a high-copy suppressor of temperature-sensitive prp2 mutants (Last RL, Maddock JR, Woolford JL Jr, 1987, Genetics 117:619-631). We have characterized the function of Spp2p in vivo and in vitro. Spp2p is an essential protein required for the first RNA cleavage reaction in vivo. Depletion of Spp2p from yeast cells results in accumulation of unspliced pre-mRNAs. A temperature-sensitive spp2-1 mutant accumulates pre-mRNAs in vivo and is unable to undergo the first splicing reaction in vitro. However, spliceosomal complexes are assembled in extracts prepared from the mutant. We show that Spp2p function is required after spliceosome assembly but prior to the first reaction. Spp2p associates with the spliceosome before the first RNA cleavage reaction and is likely to be released from the spliceosome following ATP hydrolysis by Prp2p. The Prp2 and Spp2 proteins are capable of physically interacting with each other. These results suggest that Spp2p interacts with Prp2p in the spliceosome prior to the first cleavage-ligation reaction. Spp2p is the first protein that has been found to interact with a DEAD/H box splicing factor.

Adenosine Triphosphate↗
PubMed1995

Doxazosin for the treatment of benign prostatic hyperplasia in patients with mild to moderate essential hypertension: a double-blind, placebo-controlled, dose-response multicenter study.

A total of 248 hypertensive patients 45 years old or older with benign prostatic hyperplasia (BPH) was included in this 16-week, multicenter, double-blind, placebo-controlled, parallel-group dose-response study. Doxazosin, a selective alpha 1-adrenoceptor antagonist, produced a significant increase in maximum urinary flow rate (2.3 to 3.6 ml. per second) at doses of 4 mg., 8 mg. and 12 mg., and in average flow rate (8 mg. and 12 mg.) compared with placebo. The increase in maximum flow rate was significant with doxazosin versus placebo within 1 week of initiating double-blind therapy. Doxazosin compared to placebo significantly decreased patient-assessed total, obstructive and irritative BPH symptoms. Blood pressure was significantly lower with all doxazosin doses compared with placebo. Adverse events, primarily mild to moderate in severity, were reported in 48% of patients on doxazosin and 35% on placebo. Our results strongly support the use of doxazosin as a nonoperative therapeutic alternative in the management of uncomplicated BPH. Doxazosin would also be particularly useful in the management of patients who have BPH and hypertension.

Aged↗
PubMed1994

Short-term freedom from disease progression after I-125 prostate implantation.

PURPOSE: To evaluate short-term clinical and chemical disease progression following computed tomography (CT)-based transperineal I-125 prostate implantation. METHODS AND MATERIALS: Sixty-two patients with clinical Stage T1 or T2 prostatic carcinoma had outpatient, CT-based transperineal I-125 prostate implantation and have been followed for 6-55 months (median: 19 months). Fifty-six patients had an elevated prostate specific antigen (PSA) before implantation (> 4.0 ng/mL). Twenty patients had well-differentiated tumors, 39 were moderately differentiated, 2 were poorly differentiated, and 1 was indeterminate. A total of 32-73 mCi I-125 was implanted (median: 47 mCi). The prescribed minimum prostatic dose was 140-160 Gy, and the actual matched peripheral dose ranged from 109-258 Gy (median: 160 Gy). Lymph node dissection or postimplantation prostatic biopsies were not routinely performed. RESULTS: Of 54 patients with an elevated PSA prior to implantation and no prior hormonal treatment, 96% returned to normal within 24 months of treatment. In 85% of patients, the PSA fell below 2.0 ng/mL and in 74% of patients, the PSA value fell to below 1.0 ng/mL. Seven patients had disease progression, one of whom has an isolated, rising PSA. The actuarial rate of chemical (rising PSA) or clinical failure at 3 years following implantation was 17%. Of 38 patients who were sexually potent prior to implantation, 81% remained potent at 3 years. Five patients developed radiation-induced rectal ulcerations, 11-22 months following implantation. Three patients required a transurethral resection of the prostate for postimplant urinary symptoms. CONCLUSIONS: The short-term clinical and chemical freedom-from-progression rates following I-125 implantation are comparable to that achieved with prostatectomy, with high preservation of sexual potency and moderate morbidity.

Aged↗
PubMed1994

Fluoroscopic visualization of the prostatic urethra to guide transperineal prostate implantation.

PURPOSE: To describe a novel way to assure proper needle positioning within the prostate during transperineal implantation, using the urethra as the primary radiographic landmark. METHODS AND MATERIALS: Preoperative computerized tomography (CT) images through the prostate are used to plan optimal transperineal needle-seed placement. When performing the procedure, a Foley catheter, with radio-opaque wire is used to visualize the prostatic urethra fluoroscopically in anterior-posterior and lateral projections. Proper needle placement is determined by their position relative to the urethra. RESULTS: Sixty patients have been implanted with this method at Memorial Sloan-Kettering Cancer Center from 1990-1992. CONCLUSION: The method described here is an improvement over previously described CT-based techniques. It could be used to supplement or replace ultrasound imaging.

Brachytherapy↗
PubMed1994

Quantifying the effect of dose inhomogeneity in brachytherapy: application to permanent prostatic implant with 125I seeds.

PURPOSE: To quantitate the influence of dose inhomogeneity on brachytherapy efficacy. METHODS AND MATERIALS: A computed tomography-based system of planning, implementation and evaluation was used to generate tumor-specific dose-volume histograms of eight permanent 125I implants of prostate cancers. The radiobiological effect was then assessed, voxel by voxel, in terms of the biologically effective dose and the associated cell inactivation. The overall cell survival of the entire target volume was then computed. To evaluate the influence of inhomogeneity, the dose-volume histogram was modified in an iterative fashion, with the corresponding surviving fraction calculated after each step. Specifically, the volume in the highest dose bin was combined with that in the next bin to give a new frequency distribution from which cell survival was generated. Tumor control probability (TCP) was also used as an endpoint, using the same iterative procedure. RESULTS: Doses 20-30% higher than D99 (the dose that covered 99% of the target volume) contributed to additional cell inactivation, but still higher doses did not further increase cell kill. With homogeneous irradiation at D99 as a reference, we defined the inhomogeneity enhancement factor as the ratio of the biologic effective dose of the actual implant to that of the reference dose distribution. The calculated enhancement factors were inversely dependent on tumor potential doubling time (Tp), about 1.2-1.3 for a Tp of 30 days, and between 1.3 and 1.7 if Tp = 10 days, with higher values for implants with low D99. Dose inhomogeneity enhanced TCP. For implants with high control probabilities does significantly higher (> 20%) than the D99 value did not further enhance the tumor control probabilities. In contrast, for implants with relatively low tumor control and D99 values, the control probability continued to increase with doses significantly higher than D99, up to a dose of 2 x D99. The underlying reasons were the incorporation of patient "population averaging" in the calculation and the saturation of tumor control dose response at about 120 Gy. CONCLUSION: Dose heterogeneity in implants increased tumor cell kill and local control probability, although doses > 20% higher than the prescription dose is wasted. The increase the beneficial effect of dose inhomogeneity may be greatest when most needed.

Brachytherapy↗
PubMed1994

Treatment-related symptoms during the first year following transperineal 125I prostate implantation.

PURPOSE: To summarize the urinary, rectal, and sexual symptoms occurring during the first 12 months following 125I prostatic implantation. METHODS AND MATERIALS: Thirty-one patients with Stage T1 or T2 prostatic carcinoma were evaluated for morbidity following computed tomography-guided transperineal 125I implants from 1988 to 1991. The median total activity used was 47 mCi (range 35-73 mCi). Toxicity was evaluated using a modification of the Radiation Therapy Oncology Group grading system. RESULTS: Nocturia was the most common treatment-related symptom, reported by 80% of patients within 2 months after implantation, and persisted at 12 months in 45% of the patients. Mild dysuria developed in 48% of patients within 2 months of implantation; two patients needed analgesics for their dysuria. Terazosin hydrochloride (2-10 mg qd) provided subjective improvement of urinary symptoms in seven of eight patients in whom it was tried. Rectal urgency, soft stools, and increased frequency of bowel movements was reported by 25% of the patients within 1-2 months after implantation. The incidence of asymptomatic rectal bleeding or ulceration occurring at any time after implantation was 47%, but resolved in all patients with expectant treatment. Self-limited ulceration of the rectal mucosal occurred in 16%, but only one patient developed a prostato-rectal fistula, managed with an ileal conduit. Five of the 18 potent patients experienced discomfort on erection or ejaculation, beginning within several weeks of their implant. The discomfort resolved within 6 months in three of the patients, but persisted for 18 and 24 months in the other two. CONCLUSION: 125I implantation, as performed in this series, is generally associated with only mild-moderate genitourinary and rectal symptoms that may persist 6 months or more after implantation. Prostatic carcinoma, Brachytherapy, Morbidity.

Aged↗
PubMed1994

The menace of substandard drugs.

Numerous small pharmaceutical manufacturers in Bangladesh are marketing substandard drugs, often deliberately using inadequate levels of active ingredients. Stricter application of the national drug policy is necessary, notably in regard to the issuing of licences and the sanctions applied to firms breaking the law.

Bangladesh↗
PubMed1994

Effect of structural compliance on cavitation threshold measurement of mechanical heart valves.

An in vitro study was designed to evaluate the effect of structural compliance on cavitation threshold measurements of mechanical heart valves. Using a dual channel high speed video image analysis method, the experiment was carried out in a pulse duplicator under a single, simulated physiologic condition. Each valve was mounted on a compliance adjustable fixture. One video camera served as a displacement monitor, while the other monitored cavitation bubbles at the inflow side of the valve. On-line adjustment of the mounting compliance allowed for cavitation threshold detection with respect to compliance without influencing the testing condition. Visible cavitation bubbles disappeared when the compliance was increased. Ten 29 mm mitral valves, including two each of St. Jude Medical, Carbomedics, Edwards-Duromedics (ED), Edwards Tekna (ET) and Medtronic-Hall (MH) were tested. All the bileaflet valves tested in this study showed similar cavitation thresholds at a compliance range of 0.5-0.65 mil/lb at a dp/dt of 4,000 mmHg/sec (averaged dp/dt during valve closure). Under the same dp/dt, MH monoleaflet valves showed a higher compliance range of 3.5-3.8 mil/lb to achieve the cavitation threshold. This study demonstrated that the mounting compliance of the valve must be known and well controlled in order to quantify the cavitation threshold with respect to dp/dt. In addition, the more compliant sewing ring of the ET valve may be responsible for higher cavitation thresholds with respect to dp/dt as observed in previous studies. The present in vitro study suggests that the investigation of the sewing structural compliance may be essential for the evaluation of in vivo cavitation potential.

Aorta↗