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Biomedical subjects

D Dennison

Publications and source records attributed to D Dennison.

At least 19 recordsLinked to original sources
PubMed2005

Randomized trial of two different conditioning regimens for bone marrow transplantation in thalassemia--the role of busulfan pharmacokinetics in determining outcome.

In total, 94 patients with homozygous beta thalassemia were randomized to two different conditioning regimens: busulfan 600 mg/m2 + cyclophosphamide 200 mg/kg or busulfan 16 mg/kg + cyclophosphamide 200 mg/kg and antilymphocyte globulin (47 in each group), for bone marrow transplantation, to see whether increased myeloablation or increased immunosuppression would reduce rejection. Busulfan pharmacokinetics in determining outcome was evaluated. There was no significant difference in engraftment, graft-versus-host disease, rejection, and overall and disease-free survival in the two groups. Systemic exposure to busulfan was significantly higher in the 600 mg/m2 group, but in both groups there was a wide interindividual variation in the busulfan kinetics. Six patients rejected the graft, two in the busulfan 600 mg group and four in busulfan 16 mg group (P = 0.677 CI -0.17, 0.07), but in five patients (pharmacokinetic data not available in one patient) who rejected the graft busulfan first dose trough level (C(min)-1) was below 150 ng/ml while it was above this level in the 66 of 68 patients with successful engraftment (P < or = 0.001). This randomized trial shows that rejection is influenced by busulfan levels and suggests that monitoring of busulfan levels and dose adjustment based on first-dose kinetics may reduce the risk of rejection.

Antilymphocyte Serum↗
PubMed2004

Heterozygous methylene tetrahydrofolate reductase mutation with mild hyperhomocysteinemia associated with deep vein thrombosis.

Hyperhomocysteinemia is known to be associated with arterial occlusive vascular disease and venous thrombosis. Here, we report a young ethnic Omani patient with recurrent venous thrombosis who was found to be heterozygous for 677C-T mutation in the methyltetrahydrofolate reductase (MTHFR) enzyme. Moderate hyperhomocystenemia was also observed, in the presence of normal red cell folate and serum B12 levels. No other documented marker of hereditary thrombophilia could be demonstrated in this patient, in spite of extensive investigation on multiple occasions.

Adult↗
PubMed2001

Nerve injuries of the elbow, wrist, and hand in athletes.

Upper extremity compression neuropathies are fairly rare in athletes. Initially, most can be managed conservatively. These conditions can follow direct contusion of the tissues that overlay these peripheral nerves or can result from vigorous, repetitive, athletic activity leading to tissue swelling and ischemia with nerve compression symptoms. A complete history and physical examination, including a neurologic examination, should be paramount when treating athletes with upper extremity injuries. Early diagnosis and treatment with conservative measures such as splinting, rest, activity modification, and medications can afford the athlete an earlier return to sports. Surgery can be employed when conservative treatment fails and a specific diagnosis has been ascertained.

Athletic Injuries↗
PubMed2001

Allogeneic bone marrow transplantation in the developing world: experience from a center in India.

We describe our experience of setting up an allogeneic BMT program at the Christian Medical College Hospital, Vellore over a period of 13 years, from October 1986 to December 1999. Two hundred and twenty-one transplants were performed during this period in 214 patients, with seven patients undergoing second transplants. Indication for BMT were thalassemia major - 106 (48%), CML - 30, AML - 35, ALL - 10, SAA - 22, MDS - six and six for other miscellaneous disorders. The mean age of this patient cohort was 15.6 years (range 2-52). Graft-versus-host disease of grades III and IV was seen in 36 patients (17%) and this was the primary cause of death in 20 patients (9.2%). All patients and donors were CMV IgG positive. Sepsis was the primary cause of death in 16 patients (7.4%), 10 bacterial, four fungal and two viral. One hundred and ten of this series of patients are alive and disease free (50%) with a median follow-up of 24 months (range 2-116). These results are comparable to those achieved for patients with similar disease status in transplant units in the Western world and cost a mean of US$15 000.

Adolescent↗
PubMed2001

Glutathione S-transferase activity influences busulfan pharmacokinetics in patients with beta thalassemia major undergoing bone marrow transplantation.

Busulfan, at a dose of 16 mg/kg, is widely used in combination with cyclophosphamide as a conditioning regimen for patients undergoing bone marrow transplantation. Wide interindividual variation in busulfan kinetics and rapid clearance of the drug have been reported, especially in children. Some of the factors contributing to interpatient variability have been identified. They include circadian rhythms, age, disease, drug interaction, changes in hepatic function, and busulfan bioavailability. In this study, we demonstrate that hepatic glutathione S-transferase (GST) activity correlates negatively with busulfan maximum and minimum concentrations (Pearson's correlation r = -0.74 and -0.77, respectively) and positively with busulfan clearance (Pearson's correlation r = 0.728) in children with thalassemia major in the age range of 2 to 15 years. We also found that plasma alpha GST levels were 5 to 10 times higher in patients with thalassemia than in normal controls and age-matched leukemic patients, either reflecting extensive liver damage, elevated expression of the enzyme, or both in thalassemic patients. Plasma alpha GST concentrations showed a similar correlation with busulfan kinetic parameters to that observed for hepatic GST. The status of hepatic GST activity accounts, at least in part, for the observed interindividual variation in busulfan kinetics, while the observed association with plasma alpha GST is difficult to explain at present.

Adolescent↗
PubMed2001

A pilot study of HTLV-I infection in high-risk individuals & their family members from India.

BACKGROUND & OBJECTIVES: Human T lymphotropic virus-I (HTLV-I) has been associated with adult T cell lymphoma/leukemia (ATLL). There are Indian studies on HTLV-I infection among people with sexually transmitted infection, but no large study has been conducted on individuals with haematological malignancies. In this group of individuals, serology is known to under-diagnose HTLV-I infection. This study was carried out to identify serologically and where possible with molecular techniques, HTLV-I infection in individuals with haematological malignancies. To understand the modes of transmission, family members of individuals with proven HTLV-I infection were also studied. Individuals with sexually transmitted infection (STI), blood donors and pregnant women were also studied. METHODS: Particle agglutination test was used to detect antibody to HTLV-I. HTLV genome was amplified by polymerase chain reaction (PCR) and detected with probes by digoxiginin (Dig) ELISA. RESULTS: There was no serological evidence of HTLV-I infection among the healthy blood donors and pregnant women studied. High prevalence of anti-HTLV-I antibody was identified in the patients with haematological malignancies (8 of 86 patients, 9.3%) and a lower prevalence in individuals with STI (8 of 670 individuals, 1.2%). In the STI group, all 8 individuals seroreactive to HTLV-I were coinfected with human immunodeficiency virus (HIV). In the group with haematological malignancies, three of 22 (13.6%) patients with leukemia, 3 of 11 (27.3%) with cutaneous T-cell lymphoma (CTCL) and 2 of 53 (3.8%) with lymphoma were reactive for anti-HTLV-I antibody. In this group, PCR identified all the seroreactive individuals tested. There were also seronegative infected individuals who were only identified by PCR. There was also a large number of seronegative family members who were only positive by PCR. INTERPRETATION & CONCLUSION: The study revealed a strong disease association of HTLV-I with haematological malignancies and evidence for both horizontal and vertical transmission of the infection in the Indian population. HTLV-I infection appears to be common among family members of individuals with HTLV-I associated haematological malignancies.

Adult↗
PubMed2000

Thyrotropin regulation of cyclic adenosine monophosphate production in human coronary artery smooth muscle cells.

Thyroid disease has been associated with the occurrence of pathophysiologic changes in the vasculature that may result in part from altered serum thyroid hormone and serum lipid levels. Thyrotropin (TSH) levels are also altered in thyroid disease, but a direct effect of TSH on vascular smooth muscle has not previously been considered. In the present study, human coronary artery smooth muscle cells (CASMC) were induced into two morphologically distinct forms by culturing in either (1) growth factor supplemented, 0.5% serum medium (SmGM-3) or (2) basal medium (SmBM) plus 10% fetal bovine serum (FBS). Intracellular cyclic adenosine monophosphate (cAMP) accumulation was determined by radioimmunoassay after exposure to increasing doses of bovine TSH. Cells grown in SmBM/10% FBS for 3 days exhibited a dose-dependent increase in intracellular cAMP that reached a level 10 times higher than baseline at the highest dose examined (100 mIU/mL). In contrast, cells grown in SmGM-3 medium exhibited no change in intracellular cAMP on exposure to increasing TSII. Low serum (0.5% FBS) reduced the ability of TSH to stimulate cAMP above the control value in CASMC. Pretreatment of CASMC with either transforming growth factor-beta1 (TGF-beta1) or tumor necrosis factor-alpha (TNF-alpha) lowered basal levels of cAMP production, but did not inhibit the ability of TSH to stimulate cAMP production. Human, but not rat aortic smooth muscle cells in culture also responded to TSH with a significant increase in cAMP. The results of this study suggest that TSH may exert direct effects on vascular smooth muscle mediated by adenylate cyclase activation that could conceivably affect the progression of vascular disease associated with thyroid dysfunction.

Actins↗
PubMed1999

High-performance liquid chromatographic method for quantification of busulfan in plasma after derivatization by tetrafluorothiophenol.

A high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of busulfan in plasma. Busulfan was extracted in toluene, derivatized by 2,3,5,6-tetrafluorothiophenol to obtain di-TFTP-butane, the derivatization product was then re-extracted in toluene and injected into the HPLC system with ultraviolet detection (wavelength: 275 nm). Recovery from extraction was 80%, the limit of quantification was 50 ng/ml and linearity ranged from 50 to 2000 ng/ml. In addition, forty-two samples obtained from pediatric patients treated with busulfan were analyzed by the HPLC and GC-MS assays based on the same derivatization procedure. The correlation between the di-TFTP-butane concentrations was highly significant (p<0.0001), demonstrating that the two methods were in good agreement.

Antineoplastic Agents, Alkylating↗
PubMed1999

Pharmacokinetics of oral busulphan in children with beta thalassaemia major undergoing allogeneic bone marrow transplantation.

The pharmacokinetics of busulphan were studied in 23 thalassaemic children undergoing BMT. Patients received busulphan at a dose of either 16 mg/kg with cyclophosphamide and ATG (Group A) or 600 mg/m2 (with cyclophosphamide alone) (Group B) in 16 divided doses every 6 h over 4 days. Busulphan levels were analyzed by a modified GC-MS method. The dose of busulphan/kg for patients in group B was 64% (range 56-71%) higher than that for patients in group A. The mean AUC, Css, Cmax and MRV were significantly higher in group B as compared with group A for both doses 1 and 13. There was no significant difference in Vd/F, T1/2 and Kel between the two groups. A significant decrease in AUC and Css was found between 1st and 13th doses in group B, but not in group A. The Cl/F values in group A were significantly higher than those in group B after dose 1, but not after dose 13. No increase in toxicity due to the higher dose of busulphan was noted. We conclude that busulphan at 600 mg/m2 results in much higher systemic exposure to the drug as compared to 16 mg/kg, without increase in toxicity in children with beta thalassaemia major.

Administration, Oral↗
PubMed1999

Diagnostic imaging and arthroscopy for wrist pain.

Chronic wrist pain may be evaluated by physical examination, imaging, and arthroscopy. Arthroscopy provides an attractive diagnostic and therapeutic modality in selected patients. Currently the correlation between arthroscopic findings and symptomatic pathology is not clear, because arthroscopy often identifies asymptomatic pathology. Nevertheless, the ability to diagnose and treat intra-articular pathology simultaneously provides a substantial advantage over radiographic analysis.

Arthralgia↗
PubMed1999

Van Gogh and lithium. Creativity and bipolar disorder: perspective of a writer/photographer.

Diana Dennison has suffered from manic depression since her teenage years in the 1960s but only realised that she had the condition when, in her 30s, she learnt that her uncle was manic depressive. Diana endured her low states with either no medication or with what was for her the unsatisfactory effect of tricyclic antidepressants. Her untreated hypomanic states cut a swathe through her life. She has never been hospitalised for her condition. Her marriage did not survive but her daughters did and she is now a proud and doting grandmother who skis and scuba dives. Only in the last 4 years did Diana seek help for the treatment of her condition. Diana is a free-lance writer, researcher and photographer.

Antidepressive Agents, Tricyclic↗
PubMed1998

Quantification of busulfan in plasma by gas chromatography-mass spectrometry following derivatization with tetrafluorothiophenol.

A specific and highly sensitive method has been developed for the determination of busulfan in plasma by gas chromatography-mass spectrometry using a deuterium-labeled busulfan (busulfan-d8) as internal standard. Plasma containing busulfan and busulfan-d8 were extracted with ethyl acetate and derivatized with 2,3,5,6-tetrafluorothiophenol prior to the monitoring of specific ions. The limit of quantification of the assay was 20 ng/ml and the calibration curve was linear over the range of 10 to 2000 ng/ml of derivatized busulfan. This method was in good agreement with the GC-MS assay using derivatization with sodium iodide and measuring diiodobutane. In addition, a pharmacokinetic study of busulfan was conducted in six children. The apparent oral clearance was 5.7+/-1.9 ml/kg/min and the volume of distribution was 1.0+/-0.4 l/kg and were similar to those previously reported in pediatric patients.

Alkylating Agents↗
PubMed1998

Low-dose intermittent factor replacement for post-operative haemostasis in haemophilia.

Recommendations for factor replacement therapy for postoperative haemostasis in haemophilia are often empirical and based on the physiological understanding of haemostatic requirements. This report describes the haemostatic management of patients with severe haemophilia undergoing major surgery using lower than usually recommended levels of factor replacement therapy. Eighteen adults (11 with FVIII and seven with FIX deficiency) with an average weight of 52 kg (range: 27-69) underwent 20 major surgical procedures. Factor concentrates were administered by intermittent bolus infusions. The dose of FVIII infused before surgery was 76 mu kg-1 (range: 51-113) and that of FIX was 77 mu kg-1 (range: 50-104). The preoperative levels achieved were 107% (range: 80-180) and 73% (range: 60-90), respectively. Between days 1 and 3 after surgery, an average of 29 mu kg-1 day-1 (range: 20-46) of FVIII and 23 mu kg-1 day-1 (range: 12-42) of FIX was used resulting in mean trough levels of 36% (range: 12-62) and 34% (range: 11-52), respectively. After day 4, an average of 19 mu kg-1 day-1 (range: 15-25) of FVIII and 18 mu kg-1 day-1 (range: 10-37) of FIX was administered until wound healing. The average duration of factor replacement was 11 days (range: 8-16). The mean dose of factor concentrate per patient was 260 mu kg-1 (range: 179-338) of FVIII and 300 mu kg-1 (range: 183-524) of FIX. The total amount of factor used per patient ranged from 12,380 to 19,980 units of FVIII and 8000 to 23,600 units of FIX. Only one patient had post-operative bleeding which was due to a surgical cause. It is concluded that it may be possible to use much lower than recommended levels of factor replacement therapy for postoperative haemostasis in severe haemophilia.

Adolescent↗
PubMed1996

Preventing factitious gingival injury in an autistic patient.

A 34-year-old man with a history of autism developed a deep gingival cleft. During clinical evaluation, the patient repeatedly scraped the affected area with his fingernail. The lesion's clinical features were consistent with focal inflammatory hyperplasia, periodontal disease and factitious stomatitis. This article describes the case and discusses diagnostic and behavioral issues important in treating any patient whose mental age is impaired.

Adult↗
PubMed1996

NESTROFT as a screening test for the detection of thalassaemia & common haemoglobinopathies--an evaluation against a high performance liquid chromatographic method.

The NESTROFT method (Naked Eye Single Tube Red Cell Osmotic Fragility Test) was evaluated against a high performance liquid chromatographic (HPLC) method for its usefulness in screening for beta-thalassaemia and some of the common haemoglobinopathies. Blood samples (137) from patients with suspected haemoglobin disorders were analyzed by both methods. Among the 63 patients with heterozygous beta-thalassaemia on HPLC, NESTROFT was positive for 49, 'doubtful' for 13 and negative for 1. Of the 32 patients with other haemoglobin disorders, 28 were positive on NESTROFT and 4 were 'doubtful'. Of the 42 'normal' samples, NESTROFT was positive for 6, 'doubtful' for 8 and negative for 28. This test showed an overall sensitivity of 98.7 per cent, specificity of 66.6 per cent, positive predictive value of 87 per cent and negative predictive value of 96.5 per cent. We conclude that, NESTROFT is a suitable test for screening for beta-thalassaemia and the common haemoglobinopathies seen in India. It is easy to perform, simple, inexpensive and does not require sophisticated equipment. Subjects who are NESTROFT 'positive' or 'doubtful' deserve further investigation.

Chromatography, High Pressure Liquid↗
PubMed1995

Thermal regulation of patients during the perioperative period.

Surgery patients often become hypothermic during surgical procedures. The body's thermostat, the hypothalamus, strives to maintain a normal temperature; however, when a patient's temperature drops too low, the thermoregulatory processes are suppressed, and hypothermia occurs. Cardiopulmonary bypass procedures use induced hypothermia; however, inadvertent hypothermia may occur in many other surgical procedures during which the body temperature is not systematically monitored and regulated. Hypothermia may cause complications such as protein catabolism, hypokalemia, and changes in glucose metabolism and glomerular filtration. Nursing interventions used intraoperatively to maintain a normothermic state include applying warm and temperature regulating blankets, decreasing the amount of skin exposure, and warming operating rooms.

Body Temperature Regulation↗