Posttransplantation Kaposi sarcoma-experience in a patient receiving FK-506 and MMF.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
C Chuang
Publications and source records attributed to C Chuang.
The natural history and treatment of acquired hemidystonia: report of 33 cases and review of the literature.
OBJECTIVE: To evaluate the natural history and response to treatment in hemidystonia. METHODS: 190 Cases of hemidystonia were identified; 33 patients in this series and 157 from the world literature. Data was collected on aetiology, age of onset, latency, lesion location, and response to treatment. RESULTS: The most common aetiologies of hemidystonia were stroke, trauma, and perinatal injury. Mean age of onset was 20 years in this series and 25.7 years in the literature. The average latency from insult to dystonia was 4.1 years in this series and 2.8 years in the literature, with the longest latencies occurring after perinatal injury. Basal ganglia lesions were identified in 48% of cases in this series and 60% of the cases in the literature, most commonly involving the putamen. Patients experienced benefit from medical therapy in only 26% of medication trials in this series and in only 35% of trials in the literature. In the patients reported here, the benzodiazepines clonazepam and diazepam were the most effective medications with 50% of trials resulting in at least some benefit. In the literature, anticholinergic drugs were most effective with 41% of trials resulting in benefit. Surgery was successful in five of six cases in this series and in 22 of 23 cases in the literature. However, in 12 cases, results were transient. CONCLUSIONS: The most common cause of hemidystonia is stroke, with the lesion most commonly involving the basal ganglia. Hemidystonia responds poorly to most medical therapies, but some patients may benefit from treatment with benzodiazepines or anticholinergic drugs. Surgical therapy may be successful but benefit is often transient.
Adolescent↗
A pilot tolerability and efficacy study of levetiracetam in patients with chronic myoclonus.
Levetiracetam was recently approved as adjunctive therapy for partial onset seizures. The authors conducted an open-label trial of levetiracetam in eight patients with chronic myoclonus. Patients were assessed by using the Unified Myoclonus Rating Scale. Levetiracetam was well tolerated. Three of five patients with cortical myoclonus experienced reductions in their myoclonus scores, providing support for a larger, placebo-controlled trial in cortical myoclonus.
Adult↗
Case with both multiple system atrophy and primary progressive multiple sclerosis with discussion of the difficulty in their differential diagnosis.
Explore the source record for details and available documents.
Atrophy↗
Arm tremor in cervical dystonia differs from essential tremor and can be classified by onset age and spread of symptoms.
The pathophysiology of arm tremor in patients with cervical dystonia (CD) and its relationship to other types of tremor is unclear. In the present study, we have compared the tremor in these patients with that seen in patients with essential tremor (ET) using two neurophysiological techniques: the triphasic EMG pattern accompanying ballistic wrist flexion movements; and reciprocal inhibition between forearm muscles. During ballistic wrist flexion movements, the latency of the second agonist EMG burst was later in ET than CD patients. This suggests that the mechanism of the arm tremor in CD may differ from that in ET. There was no group difference between reciprocal inhibition in patients with ET or CD. However, there was much more variability in the data from patients with CD. Because of this, we subdivided the CD patients into two groups, group A with normal levels of presynaptic inhibition and group B with reduced or absent presynaptic inhibition. A posteriori, it turned out that the patients in these two subgroups had similar clinical symptoms, but different clinical histories. The arm tremor of patients in group A started simultaneously with torticollis (mean onset age of arm tremor 40 years +/- 20.7 SD, interval between onset of arm tremor and torticollis 0 +/- 2.9 years) whereas it began much earlier (mean onset age 14 years +/- 6 SD) and preceded onset of torticollis by a longer interval (21.6 +/- 17.5 years) in patients of group B. Patients in group A also had less co-contraction in their ballistic wrist movements between the first agonist and the antagonist burst than those patients in group B. We conclude that arm tremor in patients with CD may have a mechanism different from that seen in patients with ET. Moreover, the data imply that there are two subgroups of CD patients with arm tremor, one with a late and simultaneous onset of arm tremor and torticollis (group A), and another with an early onset of arm tremor and later development of torticollis (group B). These groups do not correspond to the currently proposed clinical subdivision of 'dystonic tremor' and 'tremor associated with dystonia'.
Adult↗
Description and dosimetric verification of the PEREGRINE Monte Carlo dose calculation system for photon beams incident on a water phantom.
PEREGRINE is a three-dimensional Monte Carlo dose calculation system written specifically for radiotherapy. This paper describes the implementation and overall dosimetric accuracy of PEREGRINE physics algorithms, beam model, and beam commissioning procedure. Particle-interaction data, tracking geometries, scoring, variance reduction, and statistical analysis are described. The BEAM code system is used to model the treatment-independent accelerator head, resulting in the identification of primary and scattered photon sources and an electron contaminant source. The magnitude of the electron source is increased to improve agreement with measurements in the buildup region in the largest fields. Published measurements provide an estimate of backscatter on monitor chamber response. Commissioning consists of selecting the electron beam energy, determining the scale factor that defines dose per monitor unit, and describing treatment-dependent beam modifiers. We compare calculations with measurements in a water phantom for open fields, wedges, blocks, and a multileaf collimator for 6 and 18 MV Varian Clinac 2100C photon beams. All calculations are reported as dose per monitor unit. Aside from backscatter estimates, no additional, field-specific normalization is included in comparisons with measurements. Maximum discrepancies were less than either 2% of the maximum dose or 1.2 mm in isodose position for all field sizes and beam modifiers.
Algorithms↗
Characterization of a chromosomally complex lung cancer cell line using multiwell fluorescence in situ hybridization.
The chromosomal characterization of a non-small cell lung cancer cell line (NCIH358) is described. This characterization was achieved using a simple, cheap and technically straightforward multiwell fluorescence in situ hybridization (FISH) method. The many and complex chromosome rearrangements identified by this method could not be defined using conventional G-banded chromosome analysis, and have not been previously described. For the detailed characterization of complex cell lines, multiwell FISH has many advantages over more technically demanding and expensive FISH techniques, and opens up the possibility of screening for consistent rearrangements, leading to the identification of unique fusion genes.
Carcinoma, Non-Small-Cell Lung↗
A tetrahedral zinc(II) complex of tris(2-pyridylethyl)amine.
The zinc ion in the title complex, [N,N'-bis(2-pyridylethyl)-2-(2-pyridyl)ethylamine-kappa 4N]zinc(II) diperchlorate, [Zn(C21H24N4)](ClO4)2, displays a distorted tetrahedral configuration. The Zn-Npy distances range from 1.979 (5) to 1.999 (5) A, while the Zn-Namine distance is 2.028 (5) A. The Npy-Zn-Npy and Npy-Zn-Namine angles range from 111.9 (2) to 119.6 (2) degrees and from 102.3 (2) to 103.4 (2) degrees, respectively. This behavior contrasts with the five-coordinate geometry normally observed in tripodal ligands of similar structure, and can be ascribed to the presence of weakly-coordinating anions and the ligand-metal chelate-ring size.
Crystallography, X-Ray↗
Diabetes mellitus after renal transplantation.
Explore the source record for details and available documents.
Adult↗
Activated function of the pyruvate dehydrogenase phosphatase through Ca2+-facilitated binding to the inner lipoyl domain of the dihydrolipoyl acetyltransferase.
Micromolar Ca2+ facilitates approximately 10-fold enhancement of pyruvate dehydrogenase phosphatase (PDP) activity by aiding the association of PDP with the dihydrolipoyl acetyltransferase (E2) component. Connected by linker regions, E2 consists of two lipoyl domains, the NH2-lipoyl domain (L1) and the interior lipoyl domain (L2), and a pyruvate dehydrogenase component binding domain surrounding a 60-mer inner core. Using recombinant constructs of L1 or L2, E2-enhanced PDP activity was markedly decreased by L2 but not by L1, effectively competing with intact E2 in Ca2+-dependent binding of PDP (half-maximal reduction at 2.0 microM L2 versus 6.7 microM E2 subunit). Using L2 fused to glutathione S-transferase resulted in direct Ca2+-dependent binding of PDP to L2 (Kd, approximately 1.7 microM L2). Affinity-bound glutathione S-transferase-L2 was used to purify PDP to homogeneity by selective binding and elution by Ca2+ chelation. The large activity enhancement of PDP by E2 was eliminated by enzymatic removal of lipoates from E2 and restored by their enzymatic reintroduction. The critical role of the L2 lipoate is not in binding of PDP to E2, since PDP was still bound by delipoylated L2, and delipoylated L2 inhibited E2-enhanced PDP activity, although lipoylated L2 was more effective in each of these tests. Thus, pyruvate dehydrogenase complex activity is increased by enhanced availability of PDP to its E2-bound, phosphorylated pyruvate dehydrogenase substrate as a consequence of the Ca2+-facilitated interchange of PDP among the mobile L2 domains and an essential (undetermined) step engaging the L2 lipoate.
Acetyltransferases↗
The migrational patterns and developmental fates of glial precursors in the rat subventricular zone are temporally regulated.
Postnatal gliogenesis in the rodent forebrain was studied by infecting subventricular zone cells of either neonates or juvenile rats with replication-deficient retroviruses that encode reporter enzymes, enabling the migration and fate of these germinal zone cells to be traced over the ensuing several weeks. Neither neonatal nor juvenile subventricular zone cells migrated substantially along the rostral-caudal axis. Neonatal subventricular zone cells migrated dorsally and laterally into hemispheric gray and white matter and became both astrocytes and oligodendrocytes. Juvenile subventricular zone cells migrated into more medial areas of the subcortical white matter and on occasion appeared in the white matter of the contralateral hemisphere, but rarely migrated into the neocortex. Juvenile subventricular zone cells almost exclusively differentiated into oligodendrocytes. Thus, the migratory patterns and the developmental fates of subventricular zone cells change during the first 2 weeks of life. When either neonatal or juvenile subventricular zone cells were labeled in vivo and then removed and cultured, some generated homogeneous clones that contained either astrocytes with a 'type 1' phenotype or oligodendrocytes, but some generated heterogeneous clones that contained both glial types. These results provide additional evidence for a common progenitor for astrocytes and oligodendrocytes and strongly suggest that temporally and spatially regulated environmental signals control the destiny of glial progenitors during postnatal development.
Animals↗
Perioperative blood transfusions and prostate cancer recurrence and survival.
This retrospective clinical study of patients with nonmetastatic prostate cancer demonstrates that patients transfused at the time of initial diagnosis or operation have a higher frequency of recurrence (54 percent) and death due to cancer (19 percent) than patients not receiving blood transfusions (recurrence rate 31 percent, p = 0.005; death rate 10 percent, p = 0.08). This difference is not explained by the transfused patients being older, having a less favorable clinical stage of disease, or less differentiated tumor histology. A multivariate analysis confirmed that the additional risk of dying from prostate cancer was 2.82-fold higher in transfused patients than in those not transfused. As in previous studies, the risk of recurrence may be greater in those receiving whole blood transfusions. Prospective studies of the association between perioperative blood transfusion and cancer recurrence are needed. For the present, prudent clinical practice should include avoidance of whole blood, fresh frozen plasma, and platelet transfusions and greater reliance on autologous blood transfusions.
Humans↗
Further evidence supporting a cause and effect relationship between blood transfusion and earlier cancer recurrence.
Studies of associations between perioperative blood transfusions and later recurrence of solid tumors have yielded conflicting results. A previous analysis of transfused patients suggested that recurrence was associated with transfusion of whole blood as opposed to red blood cell concentrates. Additional analyses were performed on patients with cancers of the colon, rectum, cervix, and prostate to determine if patients receiving whole blood, red blood cells only, or no transfusions had differing outcomes. Patients receiving 1 unit or more of whole blood had uniformly poor outcomes compared with nontransfused patients (p less than 0.001). In contrast, patients receiving only red blood cells had progressively worse recurrence and death rates with increasing numbers of transfusion, suggesting the presence of a dose-effect relationship. Employing multivariate techniques, blood transfusion of less than or equal to 3 units that included any whole blood were independently and significantly associated with earlier recurrence (p = 0.003) and death due to cancer (p = 0.02). Transfusions of less than or equal to 3 units of blood comprised solely of red blood cell concentrates were associated with no greater risk of recurrence than that seen in patients receiving no transfusion (p = 0.50). These results provide a potential explanation for the disparate results reported in studies of blood transfusion and cancer outcome. The marked difference in outcome seen between patients receiving a few units of red blood cells and comparable patients receiving even one unit of whole blood are consistent with the hypothesis that transfusion of stored blood plasma causes earlier tumor recurrence in some instances. Strategies for reducing these risks might include avoidance of whole blood transfusions when only 1-3 units are required, more conservative transfusion practice, use of autologous blood transfusions, and perhaps, use of red blood cells washed free of plasma and white cell debris. Clinical trials to test these hypotheses are urgently needed.
Colonic Neoplasms↗
Long-term survival in limited-stage small cell lung carcinoma. Experience in Rochester, New York from 1975 to 1981.
All patients with limited-stage small cell lung carcinoma (SCLC) diagnosed between January 1975 and 1981 in Rochester, New York, were collected. One hundred one patients were evaluable. By reviewing an entire community's experience with long follow-up, we were able to describe the response rates and survival in a large unselected population and compare them to results from concurrent cooperative group studies. Median survival for the entire group was 51 weeks, with only 18% alive at 130 weeks. There was no evidence for improvement in response or survival during the 6 years of study. Treatment results in the community as a whole were no different from that seen with cooperative group studies. A group who had initial surgery followed by adjuvant therapy had a significantly better survival and more long-term survivors than those not receiving surgery, but rare long-term survivors were seen with all treatment categories. Except for this small surgical subgroup, no other characteristics could be identified which were predictably associated with long-term disease-free survival. The overall poor survival of patient with localized SCLC suggests a need for the development of novel initial approaches to therapy.
Adult↗
Association between transfusion of whole blood and recurrence of cancer.
Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible.
Blood Transfusion↗
Hodgkin's disease: is there a price for successful treatment? A 25-year experience.
Three hundred-twenty patients with Hodgkin's disease (HD) were studied retrospectively to assess the impact of treatment on survival and the development of second malignant neoplasms (SMN). All stages of HD were considered. Treatment groups included XRT only, XRT + multiagent chemotherapy (MAC), XRT + single agent chemotherapy (SAC), and chemotherapy only (Chemo). MAC was subdivided into MOPP and non-MOPP regimens. Twenty-one patients developed 23 SMN, only two of which were acute leukemias. Survival was greatest for XRT only because of a large proportion of early stage HD in this group. SMN were seen in all treatment groups except Chemo only. The XRT + MAC group had a significantly elevated observed-to-expected ratio for SMN, but it was difficult to attribute this to either MOPP or non-MOPP due to very small numbers of patients. The actuarial risk of SMN for both MOPP and non-MOPP rises dramatically between 10 and 15 years, however, extrapolation cannot be done, again because of very small numbers. We conclude that there is an increased risk of SMN in patients treated aggressively for HD, but that the exact cause of SMN is difficult to determine.
Antineoplastic Agents↗
Chemoprevention of 7,12-dimethylbenz(alpha)anthracene (DMBA) induced rat mammary tumors by 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP).
We have studied the chemopreventive effectiveness of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) in 7,12-dimethylbenz(alpha)anthracene (DMBA) induced rat mammary tumors. ABPP is a biological response modifier and has various biological activities, including interferon induction, immunomodulation, and antiviral and antineoplastic properties, both in vitro and in vivo. Fifty-day-old female Sprague-Dawley rats were randomized into two groups and all received 20 mg DMBA by gastric gavage. ABPP at 200 mg/kg weight was given to one group of rats three times a week for 4 weeks, beginning 6 h before DMBA. The other group of rats received the vehicle as controls. The rats were observed for 26 weeks, with weekly measurements of tumor development, size, and weight. Interferon titers were determined on all rats 6 h after the first dose of ABPP. After tumor induction, rats treated with ABPP persistently developed a fewer number of tumors on average than those in the control group. It was found that the mean sizes of total tumor mass per rat were consistently lower in the ABPP group starting 12 weeks after the tumor induction. This reduction of tumor size in ABPP-treated rats correlates significantly with the titers of interferon. Thus, our initial study demonstrates that ABPP seems to have chemopreventive potential, even with a brief duration of treatment, in DMBA-induced rat mammary cancers.
9,10-Dimethyl-1,2-benzanthracene↗
Leukemia in Rochester (NY). A 17-year experience with an analysis of the role of cooperative group (ECOG) participation.
Every adult acute nonlymphocytic leukemia patient in Rochester, New York seen from January 1975 to January 1982 was studied. Fifty percent of the patients did not receive combination chemotherapy. Among those who did, there was a significant selection bias toward placing patients with better prognostic features on protocol. Protocol patients were also treated with higher doses of chemotherapy than nonprotocol patients. However, these factors did not completely explain the significantly better complete response (CR) rate and survival among protocol patients. Eastern Cooperative Oncology Group (ECOG) participation remained an independent variable associated with a better outcome. An improvement in CR rate was seen during the 7-year period studied as compared to that seen between 1965 and 1974. The study provided evidence that the availability and use of ECOG protocols was a positive factor in the improvement of leukemia treatment in Rochester.
Acute Disease↗