A distinct syndrome including features of systemic sclerosis, erosive rheumatoid arthritis, anti-topoisomerase antibody, and rheumatoid factor.
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Antibodies↗
Biomedical subjects
M Doran
Publications and source records attributed to M Doran.
An analysis of trypanocidal drug use in the Eastern Province of Zambia.
As part of the development of a strategy for the control of bovine trypanosomosis in Zambia, a survey was conducted to quantify and qualify the current use of trypanocidal drugs (diminazene aceturate and isometamidium chloride) in a tsetse-controlled and a tsetse-infested area of the Eastern Province. A total of 207 trypanocide users were interviewed. Questions were posed on herd structure, trypanocidal drug preference, treatment strategy, reason for treatment, method of treatment and treatment frequency. The majority of the cattle owners preferred to use diminazene aceturate rather than isometamidium chloride. Both trypanocides were mainly used to treat clinically sick animals (not necessarily infected with trypanosomes) and preference was given to the treatment of oxen and cows. The proportion of animals treated and the frequency of drug application did not differ between the two areas. Hence, in the tsetse-controlled area, a high proportion of the trypanocide treatments was inappropriate. In the tsetse-infested area, on the other hand, the treatment of clinically sick animals significantly reduced the trypanosomosis-related mortality but was insufficient to boost reproduction in cows. Despite the fact that the cattle owners administered most trypanocides themselves, evidence from the survey suggests that most of the farmers did not under-dose with either diminazene aceturate or isometamidium chloride. Moreover, other factors enhancing the development of resistance to trypanocides in trypanosomes were not present in the areas surveyed. Conclusions are drawn on the usefulness of this type of survey in determining appropriate methods to control bovine trypanosomosis.
Age Factors↗
Prevention of recurrent cytomegalovirus disease in renal and liver transplant recipients: effect of oral ganciclovir.
BACKGROUND: Although the primary treatment of symptomatic cytomegalovirus (CMV) disease in organ transplant recipients is successful in >90% of individuals, relapsing disease, particularly in those with primary infection, remains an important problem. Previously, we had observed that the rate of symptomatic recurrence was >60% in those with primary disease (seronegative for CMV prior to transplant), and approximately 20% in those who were seropositive prior to transplant. The present study was undertaken to determine whether a maintenance regimen of oral ganciclovir for 2-3 months added to the routine 14-21 days of intravenous ganciclovir would further prevent symptomatic CMV recurrence. METHODS: From May 1995 until June 1998, all kidney and liver transplant recipients with confirmed tissue-invasive CMV disease or CMV syndrome were treated with 14-21 days of intravenous ganciclovir (5 mg/kg b.i.d. with dose adjusted for renal dysfunction) followed by 2-3 months of oral ganciclovir (2 g daily). The incidence of recurrence of CMV disease and/or viremia during and after oral therapy was then determined over a mean follow-up of 530.6 days. RESULTS: Thirty-seven patients, 19 kidney and 18 liver transplant recipients, were studied; 5 had biopsy-proven tissue-invasive disease (13.5) and 32 suffered a CMV syndrome (86.5). Twenty-one of these patients (58.6) were seronegative for CMV prior to transplant and received an allograft from a seropositive donor (D+/R-). Overall, 10 patients (27.0) developed CMV recurrence. Eight of 21 patients who were D+/R- for CMV (38.1) developed recurrence as opposed to 2 of 16 patients with other serologic status (12.5) (P=0.14). Patients with recurrent CMV disease and/or viremia had a peak antigenemia assay titer during their initial CMV event of 319.2 positive cells/2 slides compared with 109.8 positive cells/2 slides for patients without recurrent CMV infection (P=0.14); the trend of having a higher peak antigenemia assay titer among patients who recurred occurred both in patients who were at risk of primary CMV infection (D+/R- for CMV) and in those who were not. Two patients developed recurrent infection with strains of CMV that were resistant to ganciclovir. CONCLUSIONS: This new therapeutic regimen of oral ganciclovir following intravenous ganciclovir slightly reduced the overall rate of recurrent CMV disease and/or viremia, but it still did not adequately prevent CMV recurrence in patients who are at risk of primary infection prior to transplant. Of particular concern, 2 patients with primary infection treated with this regimen developed ganciclovir-resistant recurrent disease.
Acyclovir↗
Safety and efficacy of granulocyte colony-stimulating factor in kidney and liver transplant recipients.
BACKGROUND: Leukopenia is not infrequently encountered following solid organ transplantation, most often in the setting of cytomegalovirus (CMV) disease and/or its treatment with ganciclovir. The present study was undertaken to determine the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) in renal and liver transplant recipients with leukopenia. METHODS: Between 1 June 1991 and 1 June 1998, patients received G-CSF for 2 indications: 1) white blood cell count (WBC) < 3000/mm3, with a decline from baseline; 2) to shorten the duration of leukopenia associated with chemotherapy. A retrospective review of the outcome of such therapy was undertaken. RESULTS: 50 patients were given 100 courses of treatment with G-CSF; 35 of 168 liver transplant recipients (20.8%), 14 of 391 kidney transplant recipients (3.6%), and 1 of 4 recipients of combined liver-kidney transplants (25.0%) received from 1 to 9 courses of G-CSF. Presumed causes of leukopenia were identified as ganciclovir in 28 cases (28.0%), CMV in 21 (21.0%), chemotherapy in 12 (12.0%), sepsis in 11 (11.0%), azathioprine in 5 (5.0%), interferon in 3 (3.0%) and other causes in 20 cases (20.0%). The median length of therapy was 10.0 days (range 1-154 days) and the average dose of daily G-CSF received was 3.9+/-1.5 microg/kg/day. The average WBC was (2.4+/-1.3 )x 10(3)/microl at the beginning of therapy, and (13.8+/-9.1) x 10(3)/microl at the end of therapy. In 7 of 100 treatments (7.0%) a WBC of 5.0 x 10(3)/microl was not reached during G-CSF therapy; in 6 of these 7 cases, G-CSF therapy lasted fewer than 4 days. The mean time needed to reach a WBC count of 5 x 10(3)/microl was 3.7+/-3.3 days among 71 patients who had daily WBC counts sent. Eight G-CSF treatments (8.0%) were followed by episodes of rejection appearing during or within 2 months of treatment; 5 of them were biopsy-documented. No relation was found between the highest WBC obtained during G-CSF therapy and the risk of rejection. Eight patients (16.0%) died while receiving G-CSF, all from infection. Six of these 8 patients were receiving G-CSF for leukopenia secondary to sepsis. Overall, 25 patients (50.0%) received 49 courses of G-CSF secondary to CMV and/or ganciclovir therapy. In 40 of 49 courses (81.6%), ganciclovir could be continued at recommended doses. Twenty-one of 22 patients (95.5%) with symptomatic CMV infection had a clinical response to ganciclovir. Sixteen of 18 patients (88.9%) treated for a CMV infection and followed with serial antigenemia assays attained microbiological cure; both patients who did not were infected with ganciclovir resistant CMV. CONCLUSION: G-CSF was well tolerated in solid organ transplant recipients. It was particularly useful in patients with CMV disease, allowing optimal ganciclovir therapy.
Adult↗
The development and validation of a radiographic grading system for the hip in ankylosing spondylitis: the bath ankylosing spondylitis radiology hip index.
OBJECTIVE: To develop a simple but reproducible radiological scoring system for the hip in ankylosing spondylitis (AS). METHODS: A consensus approach was used to develop a grading system whereby hip radiographs of 470 patients with AS were scored from 0 to 4 (normal, suspicious, mild, moderate, and severe), producing the Bath Ankylosing Spondylitis Radiology Hip Index ( BASRI-hip or BASRI-h). The system was designed to be specific for AS radiographic change at the hip and includes circumferential joint space narrowing, osteophytes, erosions, and protrusio acetabulae. This score can then be added to the BASRI-spine, forming the grading system BASRI-total, scored 2-16. Radiographs of 134 patients were used to test reproducibility. Blinded radiographs of 100 non-AS patients were included randomly to assess disease specificity. Sensitivity to change was determined using 438 radiographs from 122 patients, over 219 time intervals. RESULTS: Inter and intraobserver variation for the right and left hip showed 83-84% and 94-96% complete agreement, respectively. Disease specificity was 0.76. If non-AS patients with a total hip replacement were excluded, disease specificity was 0.83. Sensitivity to change became apparent at one year (p < 0.001). Grading the hips using a single radiograph takes seconds. CONCLUSION: BASRI-h is a reliable method for grading hip radiographic change in AS. It is disease-specific, sensitive to change, simple to use, and rapid to perform.
Female↗
Prevention of primary cytomegalovirus disease in organ transplant recipients with oral ganciclovir or oral acyclovir prophylaxis.
BACKGROUND: Optimal prophylaxis against cytomegalovirus (CMV) disease for organ transplant patients at risk for primary infection (donor seropositive, recipient seronegative, D+R-) remains to be determined. We hypothesized that prolonged oral ganciclovir therapy following intravenous therapy would provide increased protection. METHODS: A total of 155 evaluable D+R- organ transplant recipients from 13 transplant centers were entered into the study: all received intravenous ganciclovir (5 mg/kg/day) for 5-10 days and then either oral acyclovir (400 mg tid) or oral ganciclovir (1 g tid) for an additional 12 weeks. Patients were assigned to their treatment groups at a central randomization site, with a separate randomization scheme for each of the organs transplanted (kidney, heart, or liver). In the case of kidney transplants, the patients were stratified according to source of the kidney (living related vs. cadaveric donor). The primary endpoint was the incidence of CMV disease in the first six months post-transplant. RESULTS: Treatment with oral ganciclovir was associated with a significant decrease in the incidence of symptomatic disease or viremia when compared with the oral acyclovir group (32% vs. 50%, P<0.05). This difference was most marked in terms of tissue invasive disease: only 3 of 15 symptomatic patients in the ganciclovir group vs. 10 of 21 in the acyclovir group developed tissue-invasive infection (P<0.05). There was a significant difference in the time to CMV disease or viremia in the two groups: mean time 212+/-17 days post-transplant for the acyclovir group vs. 291+/-13 days for the ganciclovir group (P<0.001). The incidence of allograft rejection was 34% in the ganciclovir group and 46% in the acyclovir group (P=NS). Leukopenia was more common in the ganciclovir group (P<0.05), but in no case did it require drug discontinuation. Ganciclovir resistance did not develop in this study. CONCLUSION: Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease.
Acyclovir↗
Undifferentiated dementia, Alzheimer's disease and vascular dementia: age- and gender-related incidence in Liverpool. The MRC-ALPHA Study.
BACKGROUND: Does incidence of dementia follow the age pattern of prevalence? Is gender a risk factor? Do patterns of incidence differ between dementias? AIMS: To assess age-specific incidence rates of undifferentiated dementias, Alzheimer's disease and vascular dementia. METHOD: 5222 individuals aged > or = 65 years, were interviewed using the Geriatric Mental State/History and Aetiology Schedule. The AGECAT package was used to identify cases at three interviewing waves at two-year intervals. Diagnoses were made using ICD-10 Research Criteria and validated against neurological and psychological examination, with imaging and neuropathology on unselected subsamples. RESULTS: Incidence rates of the dementias increase with age. Age patterns are similar between Alzheimer's disease and vascular dementia. Gender appears influential in Alzheimer's disease. In England and Wales, 39,437 new cases of Alzheimer's disease (4.9/1000 person-years at risk); 20,513 of vascular dementia (2.6/1000 person-years) and 155,169 of undifferentiated dementia (19/1000 person-years) can be expected each year. CONCLUSIONS: Incidence rates for Alzheimer's disease and vascular dementia appear to behave differently, with an increased risk of Alzheimer's disease for women compared to vascular dementia.
Age Factors↗
Effect of oral acyclovir or ganciclovir therapy after preemptive intravenous ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus seropositive renal and liver transplant recipients receiving antilymphocyte antibody therapy.
BACKGROUND: Organ transplant recipients who are seropositive for cytomegalovirus (CMV) and who are treated with antilymphocyte antibody (ALA) therapy have a high rate of symptomatic CMV disease. The intravenous administration of ganciclovir therapy once daily during ALA therapy decreased the incidence from 24% to 10% in patients receiving ALA as an induction therapy and from 64% to 22% in those treated for rejection. The present study was undertaken to determine whether a more intensive and sustained antiviral regimen could be more effective. METHODS: From April 1995 to December 1997, all CMV seropositive renal and liver transplant recipients who received ALA therapy were treated with intravenously administered ganciclovir (5 mg/kg/day with dose adjusted for renal dysfunction) for the length of ALA therapy and then with orally administered acyclovir (400 mg three times/day) or ganciclovir (1 gm twice/day) for 3 to 4 months. The incidence of CMV viremia and of CMV disease was determined during the 6 months after completion of ALA therapy. RESULTS: Forty-one patients (35 renal and 6 liver transplant recipients) were studied. CMV disease occurred in 2 patients (4.9%), both of whom were treated for rejection; it occurred in 1 of 21 patients (4.8%) treated with orally administered acyclovir, and in 1 of 20 patients (5%) treated with orally administered ganciclovir. The only patient who developed CMV disease in the ganciclovir group had received only 26 days of oral antiviral therapy. No CMV disease was documented in the group of patients receiving ALA therapy as induction therapy. CMV viremia occurred in three patients in the acyclovir group (14.3%) and in one patient in the ganciclovir group (5%). Among renal transplant recipients only, 1 of 35 patients developed CMV disease (2.9%) and no case of CMV disease was documented in patients treated with orally administered ganciclovir. All six patients receiving two courses of ALA therapy each were free of CMV disease. Toxicity of the regimen was minimal, and antiviral resistance did not develop. CONCLUSIONS: Preemptive antiviral therapy with intravenously administered ganciclovir during ALA therapy and then orally administered ganciclovir for 3 to 4 months provides virtually complete protection against the excessive rate of CMV disease that occurs in CMV seropositive allograft recipients receiving ALA therapy.
Acyclovir↗
Automatic analysis of cerebral atrophy.
3D MR data obtained for 10 healthy control subjects have been used to build a brain atlas. The atlas is built in four stages. First, a set of features that are unambiguously definable and anatomically relevant need to be computed for each item in the database. The chosen features are crest lines along which the maximal principal curvature of the surface of the brain is maximal in its associated principal direction. Second, a nonrigid registration algorithm is used to determine the common crest lines among the subjects in the database. These crest lines form the structure of the atlas. Third, a set of crest lines is taken as a reference set and a modal analysis is performed to determine the fundamental deformations that are necessary to bring the individual data in line with the reference set. The deformations are averaged and the set of mean crest lines becomes the atlas. Finally, the standard deviation of the deformations between the atlas and the items in the database defines the normal variation in the relative positions of the crest lines in a healthy population. In a fully automatic procedure, the crest lines on the surface of the brain adjacent to the cerebral ventricles in a patient with primary progressive aphasia were compared to the atlas; confirmation that the brain of this patient demonstrates atrophy was provided by stereological analysis that showed that the volume of the left cerebral hemisphere is 48.8 ml (CE 2.8%) less than the volume of the right cerebral hemisphere in the region of the temporal and frontal lobes. When the amplitude of the deformations necessary to register the crest lines obtained for the patient with the atlas were greater than three standard deviations beyond the variability inherent in the atlas, the deformation was considered significant. Four of the main deformation modes of the longest crest line of the surface of the brain adjacent to the cerebral ventricles were significantly different in the patient with primary progressive aphasia compared to the atlas. The ventricles are preferentially enlarged in the left cerebral hemisphere. Furthermore, they are closer together posteriorly and further apart anteriorly than in the atlas. These observations may be indicative of the atrophy of the temporal and frontal lobes of the left cerebral hemisphere noted in the patient. Ultimately, the approach may provide a useful screening technique for identifying brain diseases involving cerebral atrophy. Serial studies of individual patients may provide insights into the processes controlling or affected by particular disease.
Aged↗
High-resolution chest CT in systemic lupus erythematosus.
OBJECTIVE: The purpose of our study was to identify high-resolution CT (HRCT) findings in patients with systemic lupus erythematosus (SLE) and to determine their significance by correlation with clinical findings, plain chest radiography, and pulmonary function testing. SUBJECTS AND METHODS: Thirty-four patients with documented SLE were prospectively studied. All patients had plain chest radiography (posteroanterior and lateral) thoracic spiral CT, HRCT, and pulmonary function testing performed. RESULTS: HRCT abnormalities were identified in 24 patients (70%), pulmonary function abnormalities were present in only 14 patients (41%), and the plain chest radiograph was abnormal in only 8 patients (24%). The most common CT findings were: interstitial lung disease (n = 11), bronchiectasis (n = 7), mediastinal or axillary lymphadenopathy (n =6), and pleuropericardial abnormalities (n =5). No correlation was found between disease activity, duration of disease, chest symptoms, drug therapy, smoking history, and the presence of abnormal HRCT findings. More importantly, no correlation was found between pulmonary function abnormalities and the presence or grade of interstitial lung disease or bronchiectasis as determined by HRCT. CONCLUSION: The results of this study, the first to describe the HRCT findings in SLE, suggest that airways disease, lymphadenopathy, and interstitial lung disease are common thoracic manifestations of SLE, whereas pleural abnormalities are less common than previously suggested. HRCT evidence of airways disease and interstitial lung disease was frequently present despite an absence of symptoms, a normal chest radiograph, and normal pulmonary function testing. HRCT provides a sensitive and noninvasive technique for detecting pulmonary involvement in SLE, with the added advantage that it can be performed in all patients, including those too compromised to undergo a surgical procedure. In patients with advanced disease, HRCT permits procedures such as bronchoalveolar lavage and lung biopsy to be directed toward areas of particular interest.
Adult↗
Induction of cellular immune responses by a murine monoclonal anti-idiotypic antibody recognizing the 791Tgp72 antigen expressed on colorectal, gastric and ovarian human tumours.
There is accumulating evidence that cellular rather than antibody responses are more effective for tumour rejection. It is therefore important to screen anti-idiotypic (anti-id) antibodies for their ability to stimulate anti-tumour T-cell responses. The human anti-id monoclonal antibody (MAb) 105AD7 stimulated both delayed-type hypersensitivity (DTH) responses in animals and antigen-specific blastogenesis and IL-2 induction in advanced cancer patients. It may not be necessary to use human anti-id antibodies as murine anti-id antibodies, which elicit DTH responses against immunodominant human T-cell epitopes and may be just as useful in the clinic. We have therefore produced a murine anti-id antibody to the same MAb as was used to generate the human anti-id antibody and screened it for its ability to generate cellular anti-tumour immune responses. Low-dose immunization with the murine anti-id MAb NCRC60, which recognises the paratope of the anti-791Tgp72 MAb 791T/36, induced DTH responses to 791Tgp72-expressing tumour cells but not to antigen-negative cells. DTH responses with no detectable antibody responses were induced with 5 micrograms of anti-id NCRC60 without adjuvant. Addition of either complete Freund's adjuvant or Quil A did not enhance DTH responses. However, when the anti-id NCRC60 was linked to KLH and injected in the presence of Freund's adjuvant anti-anti-id antibodies and anti-791Tgp72 antibodies were induced. NCRC60 anti-id was also capable in vitro of priming human T cells from cancer patients to proliferate in response to secondary stimulation with 791Tgp72-expressing tumour cells, suggesting that it may have therapeutic potential in cancer patients.
Animals↗
Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial.
OBJECTIVE: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial. SETTING: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). PATIENTS: One hundred forty-one liver transplant recipients completed the study. INTERVENTION: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. MEASUREMENTS: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. RESULTS: Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). CONCLUSION: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.
Acyclovir↗
Trimethoprim-sulfamethoxazole compared with ciprofloxacin for the prevention of urinary tract infection in renal transplant recipients. A double-blind, randomized controlled trial.
BACKGROUND: Prophylaxis with low-dose trimethoprim-sulfamethoxazole has been shown to be cost-effective in the prevention of urinary tract infections, pyelonephritis, urosepsis, and pneumocystis pneumonia in renal transplant recipients. Ciprofloxacin, effective against almost all urinary tract pathogens in this patient population, represents a promising alternative prophylactic agent for patients unable to tolerate trimethoprim-sulfamethoxazole due to toxicity. METHODS: We conducted a randomized, double-blind trial to compare low-dose trimethoprim-sulfamethoxazole with ciprofloxacin for the prevention of urinary tract infections in renal transplant recipients. Patients received either ciprofloxacin (250 mg) or trimethoprim-sulfamethoxazole (80 mg trimethoprim, 400 mg sulfamethoxazole) daily for 6 months following transplantation. Treatment was considered successful if patients completed the 6-month course and 3-month follow-up period without evidence of urinary tract infection or drug-related toxicities. RESULTS: Of 103 eligible patients, 51 received ciprofloxacin and 52 received trimethoprim-sulfamethoxazole. At 6 months, treatment was successful in 75% (38 of 51) receiving ciprofloxacin and 71% (37 of 52) treated with trimethoprim-sulfamethoxazole (P = 0.87, relative risk 1.04, 95% confidence limits 0.83 to 1.33). Thirteen patients (25%) receiving trimethoprim-sulfamethoxazole withdrew from the study-4 for resistant urinary tract infection and 9 for drug-related toxicity, while 3 (6%) of the patients receiving ciprofloxacin withdrew because of drug-related toxicity (P = 0.016, relative risk of urinary tract infection or adverse event 0.24, 95% confidence limits 0.07 to 0.78). At 9 months, all 38 patients who completed the 6-month course of ciprofloxacin remained free of urinary tract infection, while an additional 4 patients who had received trimethoprim-sulfamethoxazole prophylaxis (total of 8 patients over the 9 months) developed urinary tract infections (P = 0.006, Fisher's exact test for urinary tract infection alone). Pneumocystis pneumonia occurred in a total of 7 (14%) patients who were randomized to ciprofloxacin, but 2 of the 7 had withdrawn from the study at least 2 weeks prior to the diagnosis of pneumocystis pneumonia. There were no cases of pneumocystis pneumonia in patients receiving trimethoprim-sulfamethoxazole (P = 0.006). Following completion of the study, monthly aerosolized pentamidine administered in conjunction with ciprofloxacin has provided complete protection against urinary tract infection and pneumocystis pneumonia in 30 transplant recipients unable to tolerate trimethoprim-sulfamethoxazole therapy. CONCLUSIONS: Ciprofloxacin is at least as effective as trimethoprim-sulfamethoxazole in the prevention of urinary tract infection in renal transplant recipients, and is better tolerated. Ciprofloxacin prophylaxis is associated with a higher incidence of pneumocystis pneumonia than is trimethoprim-sulfamethoxazole therapy. An uncontrolled follow-up study suggests that ciprofloxacin prophylaxis combined with monthly aerosolized pentamidine may be efficacious in preventing both urinary tract infection and pneumocystis pneumonia in renal transplant recipients.
Adult↗
Symptomatic cytomegalovirus disease in the cytomegalovirus antibody seropositive renal transplant recipient treated with OKT3.
A prospective study to investigate risk factors for CMV disease was conducted in 94 renal transplant recipients. CMV disease was defined as either unexplained fever for greater than 3 days with viremia or unexplained fever for greater than 3 days with isolation of CMV from the urine or throat wash and at least one of the following: leukopenia, elevated serum alanine aminotransferase, or biopsy-proved invasive tissue infection of the lung or gastrointestinal tract. Fifty-three patients received immunosuppressive regimens consisting of prednisone and cyclosporine, with or without azathioprine. The remaining 41 patients were treated with these agents plus OKT3 (21 received OKT3 to treat rejection, 20 received OKT3 prophylactically). Thirty-seven patients were at minimal risk of CMV disease (donor and recipient seronegative for CMV); 12 patients were at risk of primary disease (donor seropositive, recipient seronegative), and 45 were at risk of reactivation disease (recipient seropositive at the time of transplantation). The incidences of CMV disease in the 3 groups were 0%, 58%, and 36%, respectively. Although the incidence of CMV disease in patients at risk of primary disease was not influenced by the immunosuppressive regimen, immunosuppression had a profound effect on the occurrence of CMV disease in CMV-seropositive transplant recipients. The incidence of CMV disease in those receiving OKT3 was 59%; but only 21% in those who did not receive OKT3. OKT3 increased the risk of CMV disease five-fold (odds ratio 5.2 (95% confidence limits 1.4-17.5)). In the CMV-seropositive patient, OKT3 was also the most important predictor of CMV disease by multivariate analysis (P less than 0.002). A pilot study of preemptive therapy with ganciclovir (2.5 mg/kg daily during OKT3 therapy) in 17 patients decreased the incidence of CMV disease without appreciable toxicity.
Adult↗
T2- and diffusion-weighted magnetic resonance imaging of a focal ischemic lesion in rat brain.
BACKGROUND AND PURPOSE: We sought to evaluate the application of T2-weighted and diffusion-weighted magnetic resonance imaging techniques in the study of a focal ischemic lesion in the rat brain. METHODS: Unilateral cortical infarcts were induced using the photosensitive dye rose bengal and 560 nm light irradiation. Magnetic resonance images were recorded from a total of 11 rats at selected intervals from 1.5 hours to several days after induction of the lesion. Parallel experiments were performed in which Evans blue dye was injected into the lesioned animals either immediately after lesion induction (n = 11) or 1 hour before the animals were killed (n = 11). The second procedure was designed to show regions of blood-brain barrier permeability to plasma proteins at the time of sacrifice, whereas the first procedure showed the accumulation and subsequent dispersion of plasma protein following disruption of the blood-brain barrier. RESULTS: Regions of the cortex highlighted by the T2-weighted images corresponded well to the pattern of dye staining seen from the first procedure while the diffusion-weighted images showed visual correspondence with the staining pattern obtained using the second procedure. CONCLUSIONS: These results illustrate the complementary use of T2-weighted and diffusion-weighted magnetic resonance imaging in discerning the pathophysiology of developing lesions.
Animals↗
Diffusion-weighted imaging of kainic acid lesions in the rat brain.
We present T2-weighted and diffusion-weighted images of kainic acid lesions in the rat brain. Our observations show improved image contrast between edematous lesions and unaffected tissue using diffusion-weighted imaging. Furthermore, we show that the anisotropic intensity changes associated with this sequence can be used to highlight white matter tracts and to provide information concerning their orientation in the rat brain.
Amygdala↗
Diffusion-weighted MRI reveals white matter tracts.
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Body Water↗
Magnetic resonance: perfusion and diffusion imaging.
The use of magnetic resonance imaging to detect normal and pathological problems of perfusion and diffusion is reviewed. Motion sensitised spin-echo images can be used to detect changes in slow flow velocity within a voxel (intravoxel coherent motion (IVCM)) as well as intravoxel incoherent motion (IVIM) effects attributable to both diffusion and perfusion. Changes have been identified in a variety of brain diseases in the absence of changes in conventional images but the techniques are very vulnerable to motion artefact of all types. More rapid and more sensitive approaches using steady state free precision and echo-planer imaging are being investigated. Anisotropic diffusion imaging enables white matter tracts to be demonstrated within the brain and spinal cord as a function of their direction because diffusion of water across axons is much more restricted than it is along them. This technique provides a unique method for localisation of lesions and displays obvious changes in disease in which diffusion becomes less restricted.
Brain↗