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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 19 recordsLinked to original sources

[A patient with chronic mucormycosis].

Rhinocerebral mucormycosis was diagnosed in a 75-year-old woman with a history of type II diabetes mellitus. This rare opportunistic infection is caused by fungi belonging to the order of Mucorales. The patient had a severe osteomyelitis of the base of the skull, resulting in complaints of headache and diplopia. She was treated with intravenous colloidal amphotericin B, surgical excision, and later with liposomal amphotericin B. She died of respiratory failure. Mucormycosis is usually a rapidly fulminant infection. This patient showed a remarkably chronic course.

Aged

Ubiquitous nuclear factors bind specifically to a 5'-region conserved in carcinoembryonic antigen-related genes.

We recently cloned members of the murine carcinoembryonic antigen (CEA) gene family, some of which are differentially expressed during placental development. By intra- and interspecies sequence comparisons, we identified an element in the putative promoter and/or 5'-nontranslated region which is conserved within all human and rodent CEA-related genes analyzed so far. Using gel retardation analysis and DNaseI hypersensitive site mapping, we now show that ubiquitously expressed nuclear factors specifically bind to the conserved region derived from the mouse gene Cea-2 in vitro and probably also in vivo. Another DNaseI hypersensitive site lies within or close to a simple sequence motif [(GGA)n] located in the first intron of Cea-2. Such sequences have been reported to play a role in the regulation of certain genes. Therefore, this analysis has identified putative regulatory regions for Cea-2 and possibly CEA-related genes in general.

Animals

A potential new technique for awake fibreoptic bronchoscopy--use of the laryngeal mask airway.

OBJECTIVE: To assess the potential use of the laryngeal mask airway (LMA) for awake diagnostic fibreoptic bronchoscopy. DESIGN: A prospective study of 50 patients presenting for awake diagnostic bronchoscopy. All patients were premedicated with pethidine and atropine. The LMA was inserted under topical anaesthesia with sedation and the quality of the subsequent laryngoscopy and bronchoscopy was assessed for both patient and bronchoscopist. SETTING AND PATIENTS: All patients over the age of 18 years who presented to Cairns Base Hospital for diagnostic bronchoscopy were asked to participate in the study. MAIN OUTCOME MEASURES: The main factors determining the suitability of the technique were insertion rate, ease of the laryngoscopy and bronchoscopy, oxygen saturation and patient acceptance. RESULTS: The LMA was inserted successfully in all patients and the bronchoscopy subsequently performed. The first time insertion rate was 72%. The mean oxygen saturation during the procedure was 98% and patients tolerated the technique. CONCLUSIONS: The potential advantages of the LMA are that it is simple to insert, avoids nasal trauma and facilitates direct laryngoscopy. It allows respiration to be monitored and oxygen to be administered. The technique may have a role to play in patients whose respiratory function is in a critical condition, but confirmation of this awaits comparative trials. A period of training is recommended in anaesthetised patients before the LMA is used for awake diagnostic bronchoscopy.

Anesthesia, Local

Assembly and analysis of cosmid contigs in the CEA-gene family region of human chromosome 19.

The carcinoembryonic antigen (CEA)-like genes are members of a large gene family which is part of the immunoglobulin superfamily. The CEA family is divided into two major subgroups, the CEA-subgroup and the pregnancy-specific glycoprotein (PSG)-subgroup. In the course of an effort to develop a set of overlapping cosmids spanning human chromosome 19, we identified 245 cosmids in a human chromosome 19 cosmid library (6-7X redundant) by hybridization with an IgC-like domain fragment of the CEA gene. A fluorescence-based restriction enzyme digest fingerprinting strategy was used to assemble 212 probe-positive cosmids, along with 115 additional cosmids from a collection of approximately 8,000 randomly selected cosmids, into five contigs. Two of the contigs contain CEA-subgroup genes while the remaining three contigs contain PSG-subgroup genes. These five contigs range in size from 100 kb to over 300 kb and span an estimated 1 Mb. The CEA-like gene family was determined by fluorescence in situ hybridization to map in the q13.1-q13.2 region of human chromosome 19. Analysis of the two CEA-subgroup contigs provided verification of the contig assembly strategy and insight into the organization of 9 CEA-subgroup genes.

Carcinoembryonic Antigen

[The thrombosis service as a source of information for studies in patients with heart valve prostheses].

A new study design was evaluated for the estimation of the incidence of thromboembolic complications, bleeding complications and endocarditis in patients with prosthetic heart valves. Thromboembolism is a serious complication in patients with artificial heart valves. Consequently lifelong anticoagulation therapy is indicated for such patients. In the Netherlands the intensity of the anticoagulation is monitored by a network of regional anticoagulation services. The computerized patient information system of the Leiden anticoagulation service was used for a two year follow-up study of patients with mechanical heart valves. In these years anticoagulation was monitored in 273 patients with a total follow-up period of 442 patient-years. The incidence figures for thromboembolism, bleeding complications and endocarditis were 0.9/100 patient-years, 5.6/100 patient-years and 0.2/100 patient-years, respectively. The findings are similar to those of classical follow-up studies. This method is not suitable for detection of the direct early postoperative mortality or for follow-up of patient with heterografts. We conclude that the detection and follow-up by means of regional anticoagulation service offers an opportunity to investigate patients with mechanical heart valves in an efficient way without notable selection.

Actuarial Analysis

Efficacy of antibiotic prophylaxis for prevention of native-valve endocarditis.

Whether antibiotic prophylaxis can prevent bacterial endocarditis is hotly debated. In an attempt to settle this issue, we have assessed the efficacy of prophylaxis for bacterial endocarditis on native valves in a nationwide, case-control study in the Netherlands. Cases were patients with known cardiac disease in whom endocarditis developed within 180 days of a medical or dental procedure for which prophylaxis was indicated. Of a total of 438 patients with endocarditis diagnosed during 2 years, 48 were eligible for the study. Controls were patients with the same cardiac status in whom endocarditis did not develop within 180 days of a similar procedure; of a total of 889 controls from five hospitals, 200 were eligible. Overall, about 1 in 6 patients in both groups had received prophylaxis. The best estimate of protective efficacy was 49% for first-ever endocarditis occurring within 30 days of a procedure. Endocarditis developed within 30 days of a procedure in only 13% of patients with a previously diagnosed heart lesion which predisposed to the disease. The findings suggest that strict adherence to generally accepted recommendations for prophylaxis might do little to decrease the total number of patients with endocarditis in the community.

Adolescent

Epidemiology of bacterial endocarditis in The Netherlands. I. Patient characteristics.

BACKGROUND: Studies of the epidemiology of bacterial endocarditis are usually based on a retrospective review of medical records from referral centers serving diverse patient populations. These studies are therefore likely to suffer from selection bias. We conducted a nationwide prospective epidemiologic study of endocarditis in the Netherlands. METHODS: During a 2-year period, all cases of consecutively hospitalized patients with suspected endocarditis in the Netherlands were reported to us. While hospitalized, patients were visited for an in-person interview and a review of the medical record. RESULTS: Of 559 episodes, 438 met the criteria for endocarditis; these included 89 episodes of prosthetic valve endocarditis and 349 episodes of native valve endocarditis. Adjusted for age- and sex-specific population figures, the incidence was 19 per million person-years. The incidence increased significantly with age, and men were more often affected than women (266 and 172 cases, respectively). Rheumatic and congenital cardiac lesions formed most of the underlying heart diseases. Mitral valve prolapse was present in only 29 patients with native valve endocarditis (8.3%). A history of intravenous drug abuse was present in 32 patients (7.3%). Viridans streptococci, staphylococci, and enterococci together constituted 86% of the isolated bacterial strains. Only 1.1% of the patients had culture-negative endocarditis. Overall case fatality was 19.7% and varied widely according to causative microorganism. CONCLUSION: The distribution of causal microorganisms, the case fatality rate, and the incidence rate of endocarditis are age related. Therefore, a meaningful comparison of data is only possible between population-based cohorts of patients with endocarditis.

Age Factors

Epidemiology of bacterial endocarditis in The Netherlands. II. Antecedent procedures and use of prophylaxis.

BACKGROUND: The reported frequency with which endocarditis is ascribed to an antecedent dental or medical procedure varies from 3% to 62%. METHODS: We performed a nationwide prospective study of the epidemiology of bacterial endocarditis in the Netherlands. During a 2-year period, all consecutively hospitalized patients suspected of having endocarditis were visited while still hospitalized for a review of the medical record and an in-person interview that focused on antecedent procedures and administered prophylaxis. All information was checked with pharmacists and dental and medical practitioners. RESULTS: Of 427 patients with late prosthetic or native valve endocarditis, 275 were eligible for antibiotic prophylaxis because of a previously known cardiac lesion (n = 197) or a prosthetic valve (n = 78). Of these 275 patients, 64 (23.3%) had undergone a procedure with an indication for prophylaxis within 180 days of onset; in 31 (11.3%) the procedures had been within 30 days of onset. Antibiotic prophylaxis had been administered to 17 (26.6%) of the 64 patients and to eight (25.8%) of the 31 patients. CONCLUSION: The results indicate that medical and dental procedures cause only a small fraction of endocarditis. The majority of patients develop the disease along other routes. For an incubation period of 180 days, full compliance with prophylaxis might have prevented endocarditis in 47 (17.1%) of 275 patients with late prosthetic or native valve endocarditis involving a previously known cardiac lesion who underwent a procedure with an indication for prophylaxis. For an incubation period of 30 days, prophylaxis might have prevented endocarditis in 23 (8.4%) of these 275 patients, or 5.3% of all patients with endocarditis (n = 427).

Anti-Bacterial Agents

Results of operation without adjuvant therapy in the treatment of small cell lung cancer.

The role of surgery in the treatment of small cell lung cancer remains a subject of debate. We carried out a retrospective review of 87 patients with small cell lung cancer referred to one surgeon for staging and treatment. Thirty patients (34.5%) were deemed suitable for thoracotomy. Fourteen patients had stage I disease, 5 patients had stage II disease, and 11 patients had stage III disease. Twenty-eight of the 30 patients (93.3%) went on to have surgical resection. The actual overall 5-year survival in all patients who underwent thoracotomy was 43.3%. The actual 5-year survival for patients in stages I and III was 57.1% and 55.5%, respectively. No patients with stage II disease survived 5 years. We conclude that there is a small group of patients with small cell lung cancer in whom, with careful preoperative staging, the prospects of cure by operation are similar to those with non-small lung cancer.

Adult

Long-range chromosomal mapping of the carcinoembryonic antigen (CEA) gene family cluster.

A long-range physical map of the carcinoembryonic antigen (CEA) gene family cluster, which is located on the long arm of chromosome 19, has been constructed. This was achieved by hybridization analysis of large DNA fragments separated by pulse-field gel electrophoresis and of DNA from human/rodent somatic cell hybrids, as well as the assembly of ordered sets of cosmids for this gene region into contigs. The different approaches yielded very similar results and indicate that the entire gene family is contained within a region located at position 19q13.1-q13.2 between the CYP2A and the D19S15/D19S8 markers. The physical linkage of nine genes belonging to the CEA subgroup and their location with respect to the pregnancy-specific glycoprotein (PSG) subgroup genes have been determined, and the latter are located closer to the telomere. From large groups of ordered cosmid clones, the identity of all known CEA subgroup genes has been confirmed either by hybridization using gene-specific probes or by DNA sequencing. These studies have identified a new member of the CEA subgroup (CGM8), which probably represents a pseudogene due to the existence of two stop codons, one in the leader and one in the N-terminal domain exons. The gene order and orientation, which were determined by hybridization with probes from the 5' and 3' regions of the genes, are as follows: cen/3'-CGM7-5'/3'-CGM2-5'/5'-CEA-3'/5'-NCA-3'/5'-CGM1- 3'/3'-BGP-5'/3'- CGM9-5'/3'-CGM6-5'/5'-CGM8-3'/PSGcluster/qter.

Amino Acid Sequence

Over-expression of fibroblast growth factors in Xenopus embryos.

A number of forms of fibroblast growth factor (FGF) were over-expressed within Xenopus embryos by injection of synthetic FGF mRNAs into fertilized eggs. Injected embryos showed abnormalities in development which were mainly secondary to a disruption of gastrulation movements. The effects observed after injection of bFGF mRNA, however, were much less severe than those observed after injection of an altered form of bFGF mRNA which differs only by the addition of a signal sequence for secretion, or of another member of the FGF family, kFGF, which is normally efficiently secreted. All forms of FGF caused the induction of mesoderm in animal cap explants isolated from blastulae, but the amount of bFGF mRNA required to induce the formation of significant levels of mesoderm was higher by a factor of over a hundred than that of the FGFs which contain a signal sequence for secretion. Over-expressed bFGF accumulated in the nuclei of blastulae but did not necessarily cause mesoderm formation. These results show that FGFs must be secreted from the cells in which they are synthesised in order to act efficiently as mesoderm inducing factors and suggest that bFGF itself, which does not contain a signal sequence for secretion, is unlikely to be directly involved in mesoderm induction during early embryonic development.

Animals

A microbiological comparison between acute and complicated appendicitis.

Bacteria recovered from appendiceal specimens from 20 patients with acute appendicitis were compared with those recovered from 19 patients with complicated (gangrenous or perforative) appendicitis. Specimens of both peritoneal fluid and appendiceal tissue from patients with acute appendicitis yielded smaller numbers and fewer species of bacteria in culture than did specimens from patients with more complicated disease (2.3 strains per specimen for the former; 9.9 strains per specimen for the latter). Bacteria were recovered from all 13 cultures of specimens of appendiceal tissue and from 13 of 18 cultures of specimens of peritoneal fluid obtained from patients with gangrenous and perforative appendicitis; however, only eight of 17 cultures of appendiceal specimens and seven of 18 cultures of peritoneal fluid specimens from patients with acute appendicitis yielded bacteria. These findings suggest that some bacteria traverse the intact appendiceal wall prior to perforation and that progressive infection and subsequent tissue damage and necrosis allow larger numbers and varieties of bacteria to move through appendiceal wall tissue and into the peritoneal cavity.

Acute Disease

Role of tolerance in cloxacillin prophylaxis of experimental Staphylococcus aureus endocarditis.

The role of tolerance was investigated in the prophylaxis of Staphylococcus aureus endocarditis with cloxacillin in rats. The effect of a single dose of 500 mg/kg, two 80 mg/kg doses 3 h apart, and a single dose of 80 mg/kg, alone or in combination with a single dose of 4 mg of gentamicin/kg, were compared for a tolerant strain of S. aureus and its isogenic nontolerant variant. At all dosages, cloxacillin was significantly less effective in preventing endocarditis with the tolerant strain than with the nontolerant variant. With the high dose of cloxacillin or two successive lower doses, nearly complete protection could be obtained against the nontolerant strain. However, for the tolerant strain, only the combination of cloxacillin and gentamicin afforded almost complete protection. For the tolerant strain, no serum bactericidal activity was found at the time of bacterial challenge after an injection of any dose of cloxacillin. These results suggest that the in vitro phenomenon of tolerance may have relevance in vivo.

Animals

Awareness of need and actual use of prophylaxis: lack of patient compliance in the prevention of bacterial endocarditis.

Antibiotics are given before some medical and dental procedures to patients with congenital or acquired heart disease to prevent endocarditis. The majority of practitioners and patients are aware of the need for this prophylaxis, although in practice prophylaxis is administered infrequently. It is not known how often patients at risk for endocarditis undergo procedures which warrant the prophylactic administration of antibiotics, nor how often prophylaxis is actually administered to these patients. Two groups of adult patients and a group of children with a cardiac lesion predisposing to endocarditis were surveyed by either telephone interview or mailed questionnaire about awareness of the need for prophylaxis, procedures undergone within six months of the survey and the actual use of prophylaxis before these procedures. Of 455 patients surveyed, 371 (81.5%) responded, 258 (69.5%) of whom remembered receiving advice on prophylaxis. Recollection of advice ranged from 77% of those younger than sixty years to 48% of those aged sixty or older. The patients underwent 68 procedures for which prophylaxis was definitely indicated and 71 procedures with a possible indication for prophylaxis; 127 (91%) of these procedures were dental. Antibiotics were allegedly administered before the procedure to 31 patients (22%). There is marked discrepancy between recollection of the advice and actual use of prophylaxis. In view of this it is likely that patients often undergo procedures without antibiotic protection; however, only a few of these patients develop endocarditis.

Adolescent