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Biomedical subjects

R Morgan

Publications and source records attributed to R Morgan.

At least 37 records · Page 2Linked to original sources

Factors influencing plasma lipid profiles including lipoprotein (a) concentrations in renal transplant recipients.

Fasting plasma cholesterol, triglycerides, high-density lipoprotein (HDL) and apoprotein (apo) B were elevated in 214 nondiabetic renal transplant recipients when compared to a reference group. Apo (a) was slightly but not significantly lower in transplant recipients (median 118 mg/dl, range 16-1680 vs 130 mg/dl, 10-1176) and this difference could be predicted from Lp (a) isoform analysis. Cholesterol, triglyceride, apo B and apo (a) concentrations correlated negatively with creatinine clearance but none of these parameters showed a significant association with proteinuria. Patients treated with steroids had higher plasma HDL concentrations than those receiving cyclosporin monotherapy (P < 0.01). The use of diuretics was associated with raised triglycerides (P < 0.001) and cholesterol (P < 0.01) and with reduced HDL (P < 0.01) whilst patients receiving beta-blockers had significantly higher triglycerides (P < 0.01) and lower HDL levels (P < 0.02). In multiple regression analysis, age (P < 0.01), creatinine clearance (P < 0.05) and diuretic therapy (P < 0.005) were independent risk factors for increased cholesterol whilst apo (a) levels correlated negatively with creatinine clearance (P < 0.005). These results suggest that impaired renal function, steroids and non-immunosuppressive drugs contribute to lipid abnormalites in renal transplant recipients.

Adrenergic beta-Antagonists

A case of therapy-related extramedullary acute promyelocytic leukemia.

We report a patient with extramedullary acute promyelocytic leukemia (APL) occurring after radiation therapy for carcinoma of the prostate. To the authors' knowledge, this patient represents the first case of cytogenetically and fluorescence in situ hybridization (FISH) confirmed therapy-related extramedullary APL. In contrast to the majority of previously reported t-APL, this case underwent a very unfavorable course.

Aged

Unusual and unrelated polyclonality in a case of myeloid disease.

A case of myelofibrosis with myeloid metaplasia was found to have five cytogenetically unrelated clones in the marrow, four of these clones being abnormal. We present the hypothesis that the hematologic disease in this patient was caused by a genetic event not discernible microscopically (cytogenetically) and that the distinctive abnormal clones may have been generated at different anatomic sites.

Aged

Biomechanical testing of titanium self-tapping versus pretapped lag screw fixation of spiral metacarpal fractures.

Biomechanical tests of torsional loading and cantilevered bending were used to study the effects of varying screw size design of five different titanium miniscrews and microscrews in a metacarpal spiral oblique fracture model. Sixty-six fresh frozen human cadaveric metacarpal bones were subjected to torsional loading until failure, producing a spiral oblique fracture. The randomized fractured metacarpal bones were then repaired utilizing two 1.2-mm, 1.7-mm, or 2.3-mm self-tapping Leibinger lag screws; and 1.5-mm or 2.0-mm pretapped Synthes lag screws. Following repair, the specimens were then subjected to cantilevered bending or torsional loading. Failure torque and bending loads were then used to calculate failure stresses at the midshaft for torsional loading or at the proximal screw for cantilevered bending. Analysis of variance statistical analysis revealed that within the cortical thickness of bone studied, no significant difference in shear stress or axial stress was observed with increasing screw diameter and screw design.

Biomechanical Phenomena

Assessment of cellular telephone and other radio frequency exposure for epidemiologic research.

Epidemiologists are now embarking on the evaluation of the hypothesis that exposure to radio frequency energy from low-power wireless communication devices, such as portable cellular telephones, causes brain cancer and other adverse health outcomes. Even in the laboratory, exposures from radio frequency sources are difficult to quantify; their measurement in large populations for epidemiologic study is challenging. In this paper, we outline the nature and magnitude of these exposures and discuss the prospects for obtaining useful measures of exposure for epidemiologic research.

Brain Neoplasms

Influenza vaccination in the elderly.

There is overwhelming evidence for the clinical efficacy of the influenza vaccine, especially in the elderly with chronic disease, reducing mortality and hospital admissions. There is also evidence to suggest that the influenza vaccine may be beneficial in the healthy elderly. There is some evidence to suggest that the antibody response in the elderly to the vaccine may decrease with increasing age, although there are several confounding factors that have not been taken into account in many of these studies. That aside, even if antibody response is not as good as that in younger people, the evidence that vaccination saves lives and reduces morbidity in the elderly means that the vaccination should be offered to elderly patients at high risk and perhaps even to the elderly healthy population. Although vaccination of an elderly at-risk patient does not necessarily mean that that particular patient will mount an appropriate antibody response, a significant number of elderly patients will respond appropriately. Serious side-effects from vaccination are extremely rare and the more common side-effects are mild and self-limiting. Increasing the number of elderly people receiving the influenza vaccination will not only result in cost savings for the National Health Service in terms of reduced hospitalisation but, more significantly, the elderly will benefit in terms of reduced morbidity and mortality.

Aged

A winter survey of domestic heating among elderly patients.

Elderly people have a greater need for domestic heating given the time they spend at home and the decline in the body thermoregulation that occurs with ageing. The use of domestic heating by 200 mentally competent newly admitted elderly in patients was evaluated by means of a questionnaire survey. Most patients (69%) were aware of the addition of value added tax (VAT) to their fuel bill and 31% said they had reduced the amount of heating they use because of this. A third of patients (29.5%) said they had difficulty keeping warm prior to this admission. The majority of patients said they could not manage to keep warm in the winter without financial hardship. In addition, 29% said they had reduced the amount spent on food in order to pay for fuel bills. This study suggests that cold may contribute to hospital admissions in elderly patients. This should have implications for government spending and taxation policy on domestic heating.

Aged

Treatment of germ cell cancer with two cycles of high-dose ifosfamide, carboplatin, and etoposide with autologous stem-cell support.

PURPOSE: To evaluate the activity of two cycles of high-dose ifosfamide, carboplatin, and etoposide (ICE) with autologous hematopoietic progenitor cell support (aHPCS) in patients with poor-prognosis, chemotherapeutically sensitive germ cell cancer. PATIENTS AND METHODS: Twenty patients with germ cell tumor who had persistent disease or relapse from standard-risk or high-risk presentation were entered on this pilot study. The entry criteria included relapsed gonadal and extragonadal germ cell cancer unlikely to be cured by standard salvage therapy but without proven refractoriness to chemotherapy. Treatment consisted of two cycles of ICE chemotherapy with mesna uroprotection and aHPCS. On the first cycle, ifosfamide (IFX), 2 gm/m2; carboplatin, 400 mg/m2; and etoposide, 20 mg/kg, were administered on days -6, -5, and -4. On the second cycle, the doses and schedule of carboplatin and etoposide were identical, and patients with normal renal function received additional IFX, 2 g/m2 on day -3 and 1 g/ m2 on day -2. Mesna, 600 mg/m2 every 6 hours, was given until 24 hours following the final dose of IFX on each cycle, and autologous bone marrow and/or peripheral stem-cells were infused on day 0. RESULTS: All twenty patients are assessable for toxicity and current disease status. Two patients received only one cycle of therapy, one because of the development of active hepatitis C following cycle 1, and one because of renal insufficiency. No patient died as a result of protocol therapy, and no patient developed debilitating peripheral neuropathy, symptomatic hearing loss, or severe renal insufficiency requiring dialysis. The median time to recovery of > or = 500 neutrophils/microL and platelets > or = 50,000/microL was day +11 and day +15, respectively. The median maximum creatinine was 1.6 mg/dL on each treatment cycle, and there was no other significant organ toxicity. With a median follow-up of 45 months, nine patients are alive and disease-free following protocol chemotherapy. One patient with embryonal cancer developed progressive pulmonary metastases 3 months after completing high-dose therapy, underwent complete resection of lung metastases, and remains disease-free at 63+ months. Eight patients are continuously disease free at 23+ to 70+ months after protocol therapy. Eleven patients died of progressive disease between 4 and 23 months following completion of treatment. CONCLUSION: These results compare favorably to other studies in similarly selected patients undergoing salvage therapy with one or two cycles of chemotherapy containing high-dose carboplatin and etoposide with or without cyclophosphamide (CTX) or IFX. The excellent safety and tolerability profile of this regimen and its encouraging activity in poor-prognosis patients make it worthy of further study as part of initial therapy in randomized protocols for high-risk disease and early in the treatment of relapsed germ cell cancer.

Adult

Laparoscopic anatomy of the abdomen in dorsally recumbent horses.

OBJECTIVES: To provide an accurate and detailed description of the laparoscopic anatomy of the abdomen of horses positioned in dorsal recumbency and to compare those observations with laparoscopic anatomy of standing horses. The effects of laparoscopy and positional changes on arterial blood pressure and blood gas values also were investigated. DESIGN: Descriptive anatomic study. SAMPLE POPULATION: Laparoscopy was performed on 6 horses (2 mares, 2 geldings, and 2 stallions) to record the normal laparoscopic anatomy of the abdomen in dorsal recumbency. PROCEDURE: Feed was withheld from all horses for 36 hours. Horses, under general anesthesia, were examined in horizontal and inclined positions (head-up and head-down). Intermittent positive-pressure ventilation was used, arterial blood pressure was continuously monitored, and samples for arterial blood gas measurements were taken at intervals. RESULTS: The main structures of diagnostic relevance observed in the caudal region of the abdomen were the urinary bladder, mesorchium and ductus deferens (left and right), left and right vaginal rings, insertion of the pre-pubic tendon, random segments of jejunum and descending colon, pelvic flexure of the ascending colon, body of the cecum, and cecocolic fold. The main structures observed in the cranial region of the abdomen were ventral surface of the diaphragm, falciform ligament and round ligaments of the liver, ventral portion of the left lateral, left medial, quadrate, and right lateral lobes of the liver, spleen, right and left ventral colons, sternal flexure of the ascending colon, apex of the cecum, and stomach. CONCLUSIONS: Alterations in cardiovascular and respiratory function in response to pneumoperitoneum and various positional changes indicated the need for continuous and thorough anesthetic monitoring and support. Comparison of anatomic observations made in dorsally recumbent, inclined horses with those reported for standing horses should enable practitioners to make patient positioning decisions that best suit access to specific visceral structures. Development of special instrumentation for manipulation of the viscera in horses, particularly the intestinal tract, would increase the diagnostic and therapeutic capabilities of laparoscopy during dorsal recumbency.

Abdomen

Plasma cobalamin levels affect information processing speed in a longitudinal study of HIV-1 disease.

OBJECTIVE: To determine whether information processing speed is influenced by change in plasma cobalamin status in human immunodeficiency virus type 1 disease. DESIGN: A longitudinal study, using autoregression, to evaluate the relationship between plasma cobalamin status and change in information processing speed assessed by Posner Letter Matching, Sternberg Short-Term Memory Search, Figure Visual Scanning and Discrimination of Pictures, and continuous paired associates learning tasks. SETTING: University of Miami (Fla) School of Medicine from fall 1987 through summer 1991. PARTICIPANTS: Eighty-four human immunodeficiency virus type 1-infected homosexual men aged 20 to 55 years. None of the subjects displayed acquired immunodeficiency syndrome-defining symptoms at baseline; over the course of the study, 9.5% progressed to acquired immunodeficiency syndrome. MAIN OUTCOME MEASURES: Biochemical measurement of plasma cobalamin; performance on information processing speed tasks. RESULTS: Significant improvement in the Posner Letter Matching NI-PI (Name Identity minus Physical Identity) differential was associated with becoming cobalamin adequate or remaining adequate. Becoming cobalamin deficient, in contrast, was associated with a significant decline in the speed of accessing overlearned name codes. CONCLUSION: Normalization of plasma cobalamin inadequacy in human immunodeficiency virus type 1 disease may provide significant improvement in the speed of retrieving overlearned information from long-term memory.

Adult

Agrin mRNA variants are differentially regulated in developing chick embryo spinal cord and sensory ganglia.

Agrin is a synapse-organizing protein synthesized and externalized by motor neurons in the spinal cord, which organizes the postsynaptic apparatus of the developing neuromuscular junction. Agrin mRNA in the nervous system consists of several alternatively spliced variants. Splicing of agrin gene transcripts at the major site of variability results in four variants: encoding 8 (B8) or 11 (B11) amino acid inserts, both (B19), or predominant variant (B0) without inserts. The insert-containing variants are neuron specific and encode agrin proteins with greater synapse-organizing activity than the B0 variant. Here, we report the localization and developmental regulation of agrin mRNA variants in chick embryo spinal cord and dorsal root ganglia. In situ hybridization using antisense oligodeoxynucleotide (ODN) probes specific for the B8 and B11 sequences shows that the neuron-specific variants are concentrated in ventrolateral cells of the chick embryo spinal cord, presumably motor neurons, beginning at embryonic day 4 (E4). By E14, the insert-containing mRNAs are found almost exclusively in presumptive motor neurons. These variants are also found in dorsal root ganglia and sympathetic ganglia, but not in non-neural tissues. Analysis by polymerase chain reaction showed that the B11 and B19 mRNA variants appeared in spinal cord at E4, whereas the B8 variant was first seen at E14. During development, B11 decreased and disappeared by E20, whereas B8 increased from E14 to E20. A similar time course was seen in dorsal root ganglia. The greatest acetylcholine receptor-aggregating activity in the spinal cord was seen from E6 to E10, coincident with the highest proportion of B11-containing transcripts and with the peak of synaptogenesis in limb muscles. These data provide the first evidence linking appearance of the neuron-specific agrin mRNA variants with expression of the functional protein. The B11 and B19 variants appeared in E2 (stage 15) neural tubes cultured for 2 days with or without notochord and trunk tissues, indicating that there is no peripheral signal required to induce these agrin mRNA variants in developing motor neurons.

Agrin

Effects of storage on the binding of carboplatin to plasma proteins.

Plasma ultrafiltrates are routinely used in pharmacokinetic studies of carboplatin. Experiments were performed to detect and quantitate artifactual decreases in the platinum concentration of ultrafiltrates prepared from plasma samples stored at -20 degrees C and -70 degrees C. Carboplatin was added to anticoagulated, whole human blood to produce a 20 microgram/ml concentration. Plasma produced from the blood was stored frozen at either -20 degrees C or -70 degrees C. Aliquots from each storage condition were thawed and ultrafiltered once a week for up to 100 days. Platinum concentrations in ultrafiltrates and plasma were determined by flameless atomic absorption spectrometry. There was no loss of ultrafilterable platinum in plasma samples stored at -70 degrees C, whereas there was a steady decrease in free platinum concentration in ultrafiltrates prepared from plasma samples stored at -20 degrees C. These results imply that pharmacokinetic studies of carboplatin should use ultrafiltrates prepared immediately or that plasma for such studies should be stored at -70 degrees C. Storage of carboplatin-containing plasma at -20 degrees C and subsequent ultrafiltration is not acceptable, because measurement of platinum in such ultrafiltrates will be artifactually low.

Blood Preservation

Cloning of breakpoints in 3q21 associated with hematologic malignancy.

Rearrangements of band 3q21 have been well documented in leukemia. To analyze the region involved, we have isolated a normal genomic P1 clone that spans the 3q21 breakpoints derived from two leukemia patients carrying t(3;3)(q21;q26). Both breakpoints are contained within a 50-kb NotI restriction fragment, but are not identical. They are separated by 9-11 kb and may disrupt genes associated with either the proximal or distal NotI sites. We further show that one patient carried a small insertion of material from chromosome 2 in the 3q- derivative. The P1 clone will allow isolation of candidate genes for these breakpoints and investigations into the clustering of other 3q21 leukemia breakpoints.

Chromosomes, Human, Pair 3