Molecular analysis of drug resistant TB.
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Biomedical subjects
Publications and source records attributed to S Lacey.
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We assessed the usefulness of wearing masks in preventing epidemic methicillin-resistant Staphylococcus aureus (EMRSA) carriage in nursing and physiotherapy staff on two dedicated EMRSA units. In the first phase of the study, members of staff were screened for EMRSA carriage immediately before and after periods of duty using nose, throat and hand swabs. During the second phase of the study, masks were worn by staff carrying out procedures associated with significant EMRSA exposure and examined for EMRSA as described for the first phase. Both phases were conducted over a period of two months. Forty-eight percent of nursing staff were colonized with EMRSA at some time during the first phase of the study. Wearing masks significantly reduced nasal, throat and hand carriage of EMRSA (P= 0.05). We conclude that the wearing of masks by healthcare workers performing certain activities for EMRSA positive patients may prevent transient colonization and hence may be a useful intervention in the control of EMRSA in the hospital environment.
OBJECTIVES: The aim of this study was to compare the dissolution, bioavailability, and anti-Helicobacter pylori activity of bismuth subnitrate and colloidal bismuth subcitrate. This could, first, provide insights into the mechanism of action of bismuth and, second, help to develop optimal therapeutic strategies. METHODS: Solubility and aquated size of bismuth species were determined in human gastric juice, while absorption into blood and urinary excretion of bismuth was determined in volunteers. Activity against H. pylori was determined in vitro in the presence and absence of antibiotics, while H. pylori eradication was compared in vivo. RESULTS: Bismuth from colloidal bismuth subcitrate was at least 10% soluble and ultrafilterable and was absorbed in volunteers (>0.5%), whereas that from bismuth subnitrate was insoluble and not absorbed (<0.01%). Colloidal bismuth subcitrate was active against H. pylori (mean inhibitory concentration, </=12.5 microg/ml), while bismuth subnitrate was inactive (>400 microg/ml); neither was synergistic with antibiotics. With in vivo triple therapy, bismuth subnitrate was as effective as colloidal bismuth subcitrate in eradicating H. pylori (74% and 70% eradicated, respectively). CONCLUSIONS: Colloidal bismuth subcitrate, unlike bismuth subnitrate, is partially soluble, absorbed in humans, and directly toxic to H. pylori in vitro. Surprisingly, however, these preparations had similar efficacy in vivo against H. pylori within triple therapy, suggesting that bismuth compounds may also exhibit indirect antimicrobial effects. We propose that this is an effect on the gastric mucus layer. Nonabsorbable bismuth compounds should be preferentially considered in bismuth-based therapies against H. pylori, as they would minimize toxicity while maintaining efficacy.
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PURPOSE: We determined the validity of urine supersaturation assessed from 2, 24-hour urine collections from outpatients eating uncontrolled diets and receiving care at a network of treatment sites that uses a central laboratory. We compared supersaturation to stone composition to determine whether supersaturation values correlate with composition. MATERIALS AND METHODS: Two 24-hour urine samples collected from 183 patients at 6 treatment sites were shipped to a single central laboratory. Complexations and crystallizations in vitro from aging during the transport step were interrupted by pH change in acid and alkaline directions. Relevant analytes were measured, and supersaturation was calculated for calcium oxalate, calcium phosphate as brushite and uric acid. Stone analysis was done at various laboratories. RESULTS: Urine supersaturation values correlated well with stone composition. Higher calcium phosphate and uric acid supersaturation was noted when stones contained higher amounts of calcium phosphate and any uric acid, respectively. In a validation study values of relevant urine materials were unchanged after 48 hours of aging. CONCLUSIONS: Despite the need for sample transport, resulting in the inevitable aging of samples, and variations in diet and details of sample collection, supersaturation values measured in only 2, 24-hour urine collections accurately reflected stone composition. This finding indicates that supersaturation values are reasonably stable in most patients during the months to years required for stones to form. In addition, samples collected in standard practice settings and sent to a central laboratory may accurately reflect these supersaturation values.
After colectomy and ileal pouch-rectal anastomosis, pouchitis may occur. Pouchitis is a poorly defined condition with unknown etiology. The aim of this study was to develop an animal model of pouchitis. Ileal pouch-rectal anastomosis was created in Lewis and Sprague-Dawley rats. Rats were studied 4 and 8 weeks after surgery, and pouchitis was assessed by stool output, histology, and tissue myeloperoxidase (MPO) levels. Some rats were treated with allopurinol or metronidazole beginning the day of surgery. Rats with pouches demonstrated inflammation with a monocytic infiltration, luminal exudate, mucosal ulcerations, and serosal inflammation. Rats with pouches had increased anaerobic bacterial flora compared with normal ileum. After creation of pouches, Lewis rats (histology score = 8.4 +/- 1.6; MPO = 17.3 +/- 3.6, mean +/- SD) developed more severe inflammation than Sprague-Dawley rats did (histology score = 4.3 +/- 1.8; MPO = 5.5 +/- 3.6) within 4 weeks, p < 0.001 and 8 weeks after surgery, p < 0.05. Stool output was also greater in Lewis (55 +/- 7 g/kg/day) compared with Sprague-Dawley rats with pouches (43 +/- 5 g/kg/day), p < 0.05. Metronidazole treatment reduced histology score (6.0 +/- 0.5) p < 0.05 and MPO (5.9 +/- 1.6) p < 0.001 in rats with pouches compared with rats with pouches that had no treatment. Allopurinol treatment in rats with pouches reduced histology score (4.0 +/- 1.7) and MPO (3.9 +/- 1.6), p < 0.001, compared with rats with pouches that had no treatment. Ileal pouch-rectal anastomosis in rats induced inflammation within 4 weeks, demonstrated differential host genetic susceptibility, and was associated with increased number of pouch bacteria. Anaerobes, especially bacteroides sp. and free radical, may mediate inflammation. Ileal pouch-rectal anastomosis surgery in rats may be a useful animal model for the study pouchitis.
The prevalence of carpal instability in a paraplegic population was investigated to establish an association between chronic repetitive stress on the wrist and the development of such instability. Nine of 162 paraplegic patients had static carpal instability and no history of an acute injury of the wrist. The predominant pattern of instability, found in eleven wrists (six patients), was non-dissociative volar intercalated segmental instability. The prevalence of carpal instability increased with the duration of weight-bearing on the upper extremity. Eighteen per cent of the patients in whom the spinal cord injury had occurred more than twenty years before the study had carpal instability. Carpal instability in these weight-bearing upper extremities and the increase in its prevalence with the duration of the forces across the wrist demonstrate an association between chronic repetitive stress on the wrist and carpal instability.
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OBJECTIVE: To compare the short- and medium-term complications (particularly infection) of bone marrow transplantation for chronic myeloid leukemia in patients with HLA-identical sibling donors or volunteer unrelated donors. DESIGN: Retrospective review of two cohorts of patients. SETTING: Tertiary referral center. PATIENTS: One hundred three patients with chronic myeloid leukemia in first chronic phase. INTERVENTION: Patients were treated with bone marrow transplantation using marrow from HLA-identical siblings (n = 57) and volunteer donors (n = 46). MAIN RESULTS: In total, 68 patients survived a median of 22 months from bone marrow transplant (range, 7 to 81 months). The actuarial probabilities of overall survival and leukemia-free survival at 2 years for the sibling donor group were 73% (95% CI, 60% to 86%) and 72% (CI, 60% to 84%), respectively, and for the volunteer donor group, 47% (CI, 31% to 63%) and 42% (CI, 26% to 58%) (P = 0.07 and 0.05, respectively). However, after adjustment for duration of disease, overall and disease-free survival in the two donor groups did not differ significantly. A major problem was an increased incidence of severe viral infection in the volunteer unrelated donor group (19 episodes in 16 of 46 patients compared with 7 episodes in 7 of 57 sibling donor patients, P = 0.01). The actuarial incidence of chronic graft-versus-host disease (GVHD) was higher in volunteer unrelated donor patients (77% [CI, 63% to 91%] compared with 49% [CI, 35% to 63%]; P = 0.02) but that of acute GVHD was not. The median performance status of the survivors in the volunteer donor group is similar to that in the sibling donor group. The incidence of hematologic relapse in both groups so far is low. CONCLUSION: Results appear to justify the continued use of volunteer donors in chronic-phase chronic myeloid leukemia, but infection and chronic GVHD are still major problems.
Research leading to the new anti-herpesvirus compounds discussed here has come from three approaches. The first approach was directed towards improving the bioavailability of acyclovir by examining the potential of a variety of prodrugs, leading to the new compound valaciclovir hydrochloride. The second approach was to examine a large number of 5-substituted pyrimidines for activity against those viruses which were not as potently inhibited by acyclovir as are herpes simplex viruses, i.e., varicella zoster virus (VZV) and human cytomegalovirus (HCMV). This research led to the new chemical entity 882C for VZV. A third approach has been to examine drug combinations with acyclovir. This research led to the compound 348U, an inhibitor of herpes simplex virus ribonucleotide reductase which acts synergistically in combination with acyclovir. This manuscript will focus on the first two approaches leading to new compounds valaciclovir hydrochloride and 882C since Dr. Safrin details such background for 348U/acyclovir. Attempts to improve the bioavailability of acyclovir began a decade ago. Early prodrugs were compounds with alterations in the 6-substituent of the purine ring of acyclovir. The 6-amino congener required the cellular enzyme adenosine deaminase for conversion to acyclovir and the 6-deoxycongener was dependent on cellular xanthine oxidase for conversion. Neither of these prodrugs had a chronic toxicity profile in laboratory animals as good as acyclovir. Efforts were directed towards simpler esters and 18 amino acid esters were made. The pharmacokinetic profile of each prodrug was determined in rats by measuring the recovery of acyclovir in urine after oral dosing.(ABSTRACT TRUNCATED AT 250 WORDS)
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A 3-week-old infant had a massive hemangioma-like vascular neoplasm that had enlarged rapidly since being noted at birth. Less than a day after this initial evaluation the tumor underwent spontaneous ulceration and the infant had a near-fatal hemorrhage. Histologically, the tumor was a spindle cell neoplasm most consistent with the diagnosis of congenital hemangiopericytoma. Local excision appears to have been curative after almost two years of follow-up. The case is instructive in pointing out the importance of considering nonhemangioma vascular neoplasms in the evaluation of newborns with vascular tumors.
Over a 3-month period, seven patients in a paediatric oncology unit developed Pseudomonas pickettii septicaemias. The outbreak was difficult to recognize since the cases occurred at widely spaced intervals and problems were experienced with the identification of the isolates. Many of the isolates were initially misidentified on the basis of a short sugar set used in the laboratory for identification of the non-fermenting Gram-negative bacilli. Moreover, the organisms had varying sensitivity patterns. The source of the organisms proved to be vials of 'sterile' distilled water which had been used for flushing the patients' indwelling Hickman lines. No further cases occurred once the use of this water was discontinued.
The International Federation of Anti-leprosy Associations (ILEP) founded in 1966, consists of 22 autonomous nongovernmental organizations raising funds from the general public in the North for anti-leprosy work in the South. ILEP Member associations support over 800 field projects in 92 countries, in addition to over 130 research and other projects with a total annual expenditure of about US+ 60 million. 72% of the resources are spent on leprosy-control activities, 12% on training, 10% on research and 6% on socioeconomic activities. About 55% of resources are devoted to activities of national/regional leprosy programmes. ILEP-supported projects had detected over 100,000 patients in 1988. ILEP Member associations introduced WHO-recommended multidrug therapy (MDT) quite early, and the coverage for MDT in ILEP-supported projects has increased from 8% in 1984 to 35% in 1988 (271,000 patients in 1989 out of 769,000 on treatment). ILEP Member associations are currently supporting approaches towards integration of leprosy control with other services, urban leprosy programmes and social and physical rehabilitation. Thanks to their flexibility, their sense of innovation and their commitment to the worldwide anti-leprosy campaign, ILEP Members are well placed to meet the challenge of making MDT available to all leprosy patients by the year 2000.
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