[Infectious diseases in Switzerland at the dawn of the 21st Century].
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Communicable Diseases↗
Biomedical subjects
D Lew
Publications and source records attributed to D Lew.
Infusional interleukin-2 and 5-fluorouracil with subcutaneous interferon-alpha for the treatment of patients with advanced renal cell carcinoma: a southwest oncology group Phase II study.
BACKGROUND: A Phase II trial was conducted to determine the response rate of patients with advanced renal cell carcinoma to a three-drug combination of 5-fluorouracil (5-FU), interleukin-2 (IL-2), and interferon-alpha-2b (IFN-alpha). METHODS: A 2-stage accrual plan was used that was designed to determine whether response to this regimen was consistent with a true response rate of >/= 30%. The regimen was comprised of 5 treatment days weekly for 4 weeks every 6 weeks. Each weekly treatment was comprised of 5-FU, 1750 mg/m(2), continuous intravenous (i.v.) infusion over 24 hours followed by IL-2, 6 MIU/m(2)/day, continuous i.v. infusion for 4 days. IFN-alpha, 6 MU/m(2), was given subcutaneously on Days 1, 2, and 5. RESULTS: Thirty-eight patients were entered on study, 3 of whom were ineligible. Among the 35 eligible patients there were 3 confirmed partial responses (PR) and 1 complete response (CR), for an overall response rate of 11% (95% confidence interval, 3-27%). One patient considered as having a PR had minimal evidence of residual disease and was free from disease progression at > 2.5 years of follow-up, as was the patient with CR. Three additional patients not qualified as having a PR were showing signs of response at the time they were removed from protocol, and another patient who was removed from protocol early for management of an infection subsequently responded to the same regimen off protocol. Thirteen patients were considered nonassessable (NASS) for response, many of whom had multiple poor risk features and were unable to complete 1 cycle of treatment. CONCLUSIONS: This multicenter study failed to confirm an advantageous overall response rate for this three-drug regimen. However, there were two durable responses and indications of responsiveness not scored as PRs among patients with more favorable risk factor patterns, and many poor risk NASS patients. For these reasons, the response rate reported in the current study may be a conservative reflection of the effectiveness of this regimen.
Adult↗
Phase II evaluation of cisplatin and etoposide followed by mitotane at disease progression in patients with locally advanced or metastatic adrenocortical carcinoma: a Southwest Oncology Group Study.
BACKGROUND: A previous Southwest Oncology Group study demonstrated a 30% response rate with the combination of cisplatin and mitotane in the treatment of patients with metastatic adrenocortical carcinoma. Several case reports suggested that the combination of etoposide and cisplatin may be an active regimen in this disease. Because of these reports of potential activity, the authors conducted a Phase II trial evaluating the combination of etoposide and cisplatin. Due to the lack of data regarding the objective response rates to mitotane, the authors planned to evaluate the response rate to mitotane after disease progression on etoposide and cisplatin in patients with no prior mitotane therapy. METHODS: Patients with advanced, unresectable, or metastatic adrenocortical carcinoma with objectively measurable disease or biochemical abnormalities received cisplatin, 50 mg/m(2), intravenously on Days 1 and 2, and etoposide, 100 mg/m(2), on Days 1, 2, and 3. Cycles were repeated every 21 days. At the time of disease progression, patients who had not previously received mitotane received 1000 mg orally 4 times a day along with cortisone acetate and fludrocortisone acetate. RESULTS: Of the 47 patients entered onto the study, 45 were eligible. Nine patients had received mitotane previously and 36 had not. Objective responses were noted in 11% of patients (5 of 45 patients) (95% confidence interval, 3.7-24%). The median survival was 10 months. The most common toxic effects were hematologic, gastrointestinal, and neurologic. Only 16 patients with no prior mitotane therapy went on to receive mitotane at the time of disease progression. An objective response was noted in 13% of patients (2 of 16 patients). The most common toxic effects were edema and gastrointestinal effects. CONCLUSIONS: The current study demonstrates that the combination of cisplatin and etoposide has minimal activity in advanced and metastatic adrenocortical carcinoma and other treatment strategies are warranted.
Adolescent↗
Use of hydroxyapatite cement to support implants in extraction sockets.
Bioactive cements based on calcium phosphate chemistry have been developed to serve as bone substitute materials. One such commercial product, BoneSource, is a hydroxyapatite cement (HAC) used for small bone defects in the craniofacial complex. We have investigated the possibility that HAC could be used to support bone growth adjacent to dental implants placed in immediate tooth extraction sites. Variable levels of bone contact were noted up to 3 months postimplantation. Considerable loss of HAC occurred and was thought to be because of "washout" of the cement before complete cement setting. When HAC was immobile in the surgical site, the bioactive nature of the cement led to HAC resorption and bone deposition. Efforts to maintain the HAC in situ should be expanded so that the full clinical potential of the HAC can be realized.
Absorbable Implants↗
Heterologously expressed Staphylococcus aureus fibronectin-binding proteins are sufficient for invasion of host cells.
Staphylococcus aureus invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, critically depends on fibronectin bridging between S. aureus fibronectin-binding proteins (FnBPs) and the host fibronectin receptor integrin alpha(5)beta(1) (B. Sinha et al., Cell. Microbiol. 1:101-117, 1999). However, it is unknown whether this mechanism is sufficient for S. aureus invasion. To address this question, various S. aureus adhesins (FnBPA, FnBPB, and clumping factor [ClfA]) were expressed in Staphylococcus carnosus and Lactococcus lactis subsp. cremoris. Both noninvasive gram-positive microorganisms are genetically distinct from S. aureus, lack any known S. aureus surface protein, and do not bind fibronectin. Transformants of S. carnosus and L. lactis harboring plasmids coding for various S. aureus surface proteins (FnBPA, FnBPB, and ClfA) functionally expressed adhesins (as determined by bacterial clumping in plasma, specific latex agglutination, Western ligand blotting, and binding to immobilized and soluble fibronectin). FnBPA or FnBPB but not of ClfA conferred invasiveness to S. carnosus and L. lactis. Invasion of 293 cells by transformants was comparable to that of strongly invasive S. aureus strain Cowan 1. Binding of soluble and immobilized fibronectin paralleled invasiveness, demonstrating that the amount of accessible surface FnBPs is rate limiting. Thus, S. aureus FnBPs confer invasiveness to noninvasive, apathogenic gram-positive cocci. Furthermore, FnBP-coated polystyrene beads were internalized by 293 cells, demonstrating that FnBPs are sufficient for invasion of host cells without the need for (S. aureus-specific) coreceptors.
Adhesins, Bacterial↗
Southwest Oncology Group Study of paclitaxel and carboplatin for advanced transitional-cell carcinoma: the importance of survival as a clinical trial end point.
PURPOSE: The combination of paclitaxel and carboplatin for the treatment of advanced transitional-cell carcinoma (TCC) of the urothelium has promising activity and acceptable toxicity. The purpose of this trial was to evaluate the efficacy of this regimen in a cooperative group setting. PATIENTS AND METHODS: Twenty-nine patients with advanced TCC were treated every 21 days with paclitaxel 200 mg/m(2), administered as a 3-hour infusion, followed by carboplatin dosed to an area under the curve of 5. Prior systemic adjuvant or neoadjuvant platinum-based therapy was not permitted unless completed at least 1 year before enrollment. Patients were evaluated for response every three cycles, and follow-up was conducted to determine survival. RESULTS: Twenty-nine patients were enrolled and were assessable. Four (14%) had received prior adjuvant or neoadjuvant therapy. Node-only disease was present in 24%, and 76% of patients had extranodal disease. The median number of cycles received was five. Grade 4 toxicity consisted primarily of neutropenia (38% of patients). Neurologic toxicity was noted in 16 patients (grade 1 in four patients, grade 2 in five patients, grade 3 in six patients, and grade 4 in one patient). Six partial responses and no complete responses were noted, for a response proportion of 20.7% (95% confidence interval, 8% to 40%). Median progression-free survival time was 4 months, and overall survival time was 9 months. CONCLUSION: The combination of paclitaxel and carboplatin for the treatment of advanced TCC is reasonably well tolerated. However, a response proportion considerably lower than that previously reported was noted. In addition, the median survival time of 9 months was less than the survival time previously reported for patients treated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin. Although our results may reflect enrollment of patients with poor prognostic features, they also call into question the utility of this regimen.
Adult↗
[Symptoms and clinical and radiological signs predicting the bacterial origin of acute rhinosinusitis].
A minority of patients with common cold and upper respiratory tract infections have a bacterial infection and may benefit from antibiotic therapy. The present analysis set out to determine whether there were clinical symptoms or signs which could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis who are infected with pathogenic bacteria. Detailed clinical history and medical examination were obtained from 265 patients (mean age 35 years, 138 females and 127 males) presenting symptoms of upper respiratory tract infections but no fever above 38 degrees C. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae or M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Aggravating factors for severity of rhinosinusitis, such as severe nasal obstruction, inferior and/or middle turbinate hypertrophy, oedema of the middle meatus mucosa and septal defects, were not associated with the presence of bacteria. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms which were significantly associated in a multivariate model with the presence of bacteria included facial pain (p < 0.003), coloured nasal discharge (p < 0.003) and radiological maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening greater than 10 mm) (p < 0.002). This, the best predictive model, had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. We conclude that signs and symptoms of acute rhinosinusitis in patients with a mild to moderate clinical presentation are poor predictors of the presence of bacteria. In agreement with previous studies, culture of nasopharyngeal secretions may identify patients who would benefit from antibiotic treatment. Thus, antibiotic therapy should not be prescribed in the absence of bacteriological evidence.
Adolescent↗
Plasmid DNA malaria vaccine: the potential for genomic integration after intramuscular injection.
Plasmid-based (naked DNA) genetic vaccines are now entering clinical trials to test their safety and efficacy in healthy human volunteers. A safety concern unique to this new class of vaccines is the potential risk of deleterious integration into host cell genomic DNA following direct intramuscular injection. To address this issue experimentally, a preclinical safety study was conducted in mice to determine the structural nature of plasmid DNA sequences persisting in total muscle DNA at both 30 and 60 days following a single intramuscular injection of a plasmid expressing the Plasmodium falciparum circumsporozoite protein. In a protocol described for the first time, total DNA was extracted from muscle tissue and was subsequently linearized with a restriction endonuclease to enable agarose gel size fractionation of all extrachromosomal plasmid DNAs from high molecular weight mouse genomic DNA. Using PCR assays to quantitate plasmid-specific sequences, it was found that the amount of plasmid DNA persisting in muscle tissue varied but averaged about 10 fg per microgram of genomic DNA (in the range of 1500 copies per 150,000 genomes). In two of four separate experimental injections of mouse muscle, PCR assays of genomic DNA fractions indicated that agarose gel purification removed plasmid DNA down to a level of < or =3 copies per 150,000 mouse genomes. In the two other experimental samples, 3-30 copies of plasmid DNA remained associated with purified genomic DNA. The time following injection (i.e., 30 or 60 days) was not a factor in the number of copies of plasmid associating with genomic DNA and it was not possible to conclude if such sequences were covalently linked to genomic DNA or simply adventitiously associated with the genomic DNA. However, if an assumption is made that the highest level plasmid DNA found associated with genomic DNA (i.e., 30 copies) represented covalently integrated plasmid inserts and that each insert resulted in a mutational event, the calculated rate of mutation would be 3000 times less than the spontaneous mutation rate for mammalian genomes. This level of integration, if it should occur, was not considered to pose a significant safety concern.
Animals↗
Osteomyelitis.
Despite significant progress in antibiotic therapy and orthopedic surgery, osteomyelitis remains a difficult-to-treat infection that is often associated with recurrence. In this paper we summarize the most recent developments in understanding the pathogenesis of this complex disease, as well as novel means for its diagnosis and treatment.
Journal Article↗
Osteomas of the condyle associated with Gardner's syndrome causing limited mandibular movement.
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Adolescent↗
Biomechanical and morphometric analysis of hydroxyapatite-coated implants with varying crystallinity.
PURPOSE: The level of crystallinity in hydroxyapatite (HA) is thought to be responsible for its degradation in the physiologic milieu. The purpose of this study was to compare the in vivo bony response to HA coatings of varying levels of crystallinity and determine the optimum composition for promoting osseointegration. MATERIALS AND METHODS: Cylindrical implants of sand-blasted CP titanium and HA-coated titanium of 50% (low), 70% (medium), and 90% (high) crystallinity were inserted into the canine femur for 1, 4, 12, and 26 weeks. Morphometric analysis of undecalcified sections determined the percentage of bone contact with the implant surface. A pullout test was used to measure the interfacial attachment strength of the bone-implant interface. Scanning electron microscope (SEM) examination of the implant surface aided in identifying the failure mode. Coating thickness was measured under light microscopy to determine whether degradation occurred. RESULTS: No significant differences could be found in the percentage of bone contact and interfacial attachment strength between the three types of HA-coated implants throughout the four implantation periods. A significantly higher percentage of bone contact on HA-coated implants than on uncoated titanium implants was noted at 4 weeks. (ANOVA, P<.05). HA-coated implants were also found to have significantly higher interfacial attachment strength than titanium implants at 4, 12, and 26 weeks. Coating thickness decreased gradually with time. The most noticeable reduction was found on the low-crystallinity coatings during the first 4 weeks. Failure of the bone-coating-implant complex occurred mostly within the coating or near the coating-implant interface. CONCLUSIONS: HA coatings on metal implants enhance osseointegration in the early stage of bone healing and provide strong bone-bonding capability, although titanium implants had about the same level of bone contact in the later stage of healing. Crystallinity of HA coatings has no significant influence over the bone formation capacity and the bone bonding strength. However, an HA coating of higher crystallinity is more desirable in providing durability and maintaining osteoconductive properties.
Analysis of Variance↗
Virtual arthroscopy of the visible human female temporomandibular joint.
PURPOSE: This study was designed to obtain views of the temporomandibular joint (TMJ) by means of computed arthroscopic simulation (virtual arthroscopy) using three-dimensional (3D) processing. MATERIAL AND METHODS: Volume renderings of the TMJ from very thin cryosection slices of the Visible Human Female were taken off the Internet. Analyze(AVW) software (Biomedical Imaging Resource, Mayo Foundation, Rochester, MN) on a Silicon Graphics 02 workstation (Mountain View, CA) was then used to obtain 3D images and allow the navigation "fly-through" of the simulated joint. RESULTS: Good virtual arthroscopic views of the upper and lower joint spaces of both TMJs were obtained by fly-through simulation from the lateral and endaural sides. It was possible to observe the presence of a partial defect in the articular disc and an osteophyte on the condyle. Virtual arthroscopy provided visualization of regions not accessible to real arthroscopy. CONCLUSION: These results indicate that virtual arthroscopy will be a new technique to investigate the TMJ of the patient with TMJ disorders in the near future.
Arthroscopy↗
Meropenem (1.5 g/day) is as effective as imipenem/cilastatin (2 g/day) for the treatment of moderately severe intra-abdominal infections.
This multicentre, open-label, randomised trial compared meropenem (0.5 g/8 h) and imipenem/cilastatin (at the commonly used dosage of 0.5 g/6 h) in monotherapy in patients with moderately severe intra-abdominal infections (IAIs). In total, 161 patients were randomised (82 meropenem, 79 imipenem/cilastatin). The mean APACHE II scores in the two groups were 5.8 and 6.4, respectively. At the end of therapy, 65/71 (91.6%) evaluable meropenem recipients were clinically cured or improved, compared to 60/64 (93.8%) imipenem/cilastatin recipients. This difference and that in an intention-to-treat analysis (82.1 vs 86.1%, respectively), were not statistically significant. Both drugs were generally well tolerated. Thus, meropenem 0.5 g/8 h is as clinically effective and well tolerated as imipenem/cilastatin 0.5 g/6 h in moderately severe IAIs.
APACHE↗
MR imaging of the temporomandibular joint: a validation experiment in vitro.
RATIONALE AND OBJECTIVES: The authors compared magnetic resonance (MR) image quality obtained from 3- and 1-mm-thick sections in the depiction of the temporomandibular joint (TMJ) and its adjacent structures. MATERIALS AND METHODS: Eight TMJ specimens from four adult cadaver heads were depicted with MR imaging. Both 3- and 1-mm-thick sections were generated. One oral and maxillofacial radiologist, who was blinded to section thickness, evaluated the anatomic details of the images. Subsequently, the joints were surgically explored by two oral and maxillofacial surgeons, and the physical findings were recorded. RESULTS: Some statistically significant differences were found between the physical findings and the 3-mm-thick section images, while no significant differences were found with the 1-mm-thick sections. CONCLUSION: The TMJ and its adjacent structures were better depicted by thinner MR images.
Aged↗
Group A beta-hemolytic streptococcus meningitis: clinical and microbiological features of nine cases.
Group A beta-hemolytic streptococcus (GAS) meningitis is a rare disease in adults. We conducted a retrospective study to describe clinical and microbiological features of nine cases of GAS meningitis in Switzerland. Of nine patients, six had neurosurgical conditions, and five had upper respiratory tract infections. Eight cases were community-acquired. The outcome of GAS meningitis was favorable; only one patient died of neurosurgical complications. No patient presented with toxic shock syndrome. Serotyping failed to reveal a dominant strain, and genotyping revealed that two strains carried the gene encoding the streptococcal pyrogenic exotoxin C and that one strain carried the gene encoding the streptococcal pyrogenic exotoxin A. Our observations suggest that GAS meningitis in adults is associated with neurosurgical conditions and/or an upper respiratory tract infection.
Adolescent↗
Bloodstream infections caused by small-colony variants of coagulase-negative staphylococci following pacemaker implantation.
Small-colony variants (SCVs) of Staphylococcus aureus cause persistent and relapsing infections. Relatively little is known regarding infections caused by SCVs of coagulase-negative staphylococci. We report two cases of pacemaker electrode infections due to SCVs of Staphylococcus epidermidis and Staphylococcus capitis. Sequence analysis of a portion of the 16S rRNA gene (16S rDNA) confirmed the identity of the staphylococcal species as S. capitis and S. epidermidis. Isolates from cultures of blood obtained over at least a 2-week interval were compared by pulsed-field gel electrophoresis and found to be clonal even though the colony morphology was very different. Analysis for auxotrophism revealed hemin dependencies for all isolated SCVs. The two cases have several clinical and laboratory characteristics (which are also seen with S. aureus SCV infections) and strongly suggest that SCVs of coagulase-negative staphylococci must be actively sought, because they grow very slowly and can be easily missed.
Bacteremia↗
A comparative study of osseointegration of titanium implants in autogenous and freeze-dried bone grafts.
PURPOSE: This study was undertaken to compare the rate and degree of osseointegration of dental implants when placed into either autogenous corticocancellous chip or freeze-dried corticocancellous chip bone grafts. MATERIALS AND METHODS: The canine ilium was used as the model site. Thirty experimental and 15 control implants were placed in 15 dogs: autogenous versus freeze-dried corticocancellous chip bone grafts around the exposed implant surfaces. In addition to the placement of control implants, the apical portion of the grafted implants acted as their own control. The implants were harvested at 1, 2, and 3 months. The evaluation of the integration process was performed by means of light microscopy, microradiography, and histomorphometry. RESULTS: Using this model, the results indicate that at 1 month there was no statistical difference in the degree of osseointegration in the two bone grafts. At 2 months, there was a statistically greater degree of osseointegration noted in the autogenous corticocancellous chip sites than in the freeze-dried bone grafts. At 3 months, the degree of osseointegration in the two groups was 70% and 33%, respectively. At 3 months, there was virtually 100% integration with trabecular bone at the control implant sites. CONCLUSION: The results indicate that at 2 months postoperatively implants placed in an autogenous bone chip graft osseointegrate to a significantly greater degree than implants placed in a freeze-dried bone chip graft, and this difference remains at 3 months.
Animals↗
Wegener's granulomatosis presenting as oral lesions: a case report.
Wegener's granulomatosis will classically present as a triad of respiratory, kidney, and vascular involvement. The disease may run a course of rapidly progressive or mild and indolent and escape diagnosis for some time. The clinician must be aware of the possibility of Wegener's granulomatosis presenting initially with intraoral lesions. Prompt biopsies and blood studies along with the proper referrals will give the patient their best chance at a remission with the least systemic damage. We present a case of Wegener's granulomatosis that presented with oral lesions before other signs and symptoms.
Diagnosis, Differential↗