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Biomedical subjects

C Bosch

Publications and source records attributed to C Bosch.

At least 19 recordsLinked to original sources

Gemcitabine and low dose carboplatin in the treatment of elderly patients with advanced non-small cell lung cancer.

BACKGROUND: Fifty percent of lung cancers arise in patients over 65 years old and 30% in those over 70. The aim of this study was to evaluate response, survival and tolerability of the combination carboplatin-gemcitabine in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Between May 1998 and December 2000, 88 patients were included. Median age was 74 (range 65-83). Treatment consisted of gemcitabine 1250 mg/m(2) (1000 mg/m(2) in the first six patients) on days 1 and 8, and carboplatin AUC=4 on day 1, every 21 days. Prognostic factors for survival were analysed. Performance status (PS) and symptoms were evaluated before and after three and six courses. RESULTS: A total of 400 cycles were administered (median of four per patient). WHO grades 3-4 toxicities were: neutropenia in 13% of the cycles, thrombocytopenia and anaemia in 4.5 and 14.7% of patients in any cycle. There was one treatment-related death. According to the intent-to-treat analysis, 33 patients achieved objective response, 33 had stable disease, and 22 had treatment failure (progression in 18 patients). Median and 1 year survival were 9 months and 34%, respectively. Median time to progression was 8 months. Only disease stage and PS showed independent prognostic value. Comorbidity and PS displayed no close correlation. Symptom improvement was seen as follows: pain (61.7%), dyspnea (50%), haemoptysis (80%), anorexia (62.5%) and asthenia (61.5%). CONCLUSIONS: The combination carboplatin-gemcitabine at these doses is feasible in elderly patients with advanced non-small cell lung cancer. Tolerability and toxicity are acceptable. Response rate and survival stand in the range of the most active regimens. Comorbidity and PS showed prognostic independence.

Aged↗

Multicenter phase II trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer.

BACKGROUND: Irinotecan (CPT-11) and raltitrexed are active against advanced colorectal cancer (ACC), act through different mechanisms, and have only partially overlapping toxicity profiles. Phase I studies have shown that single-agent full doses of both drugs can be safely combined. The aim of this multicenter study was to assess the efficacy and toxicity of the combination in patients with 5-fluorouracil (5-FU)-refractory ACC. PATIENTS AND METHODS: Between October 1999 and December 2000, 52 patients (31 males, 21 females) with a median age of 62 years (range 39-75) were included and received CPT-11 (350 mg/m(2) as a 60-min infusion) plus raltitrexed (3 mg/m(2) as a 15-min infusion, 1 h after CPT-11), with courses repeated every 21 days. Objective response was assessed after every three courses, and treatment maintained until tumor progression or unacceptable toxicity. RESULTS: A total of 313 cycles were administered, with a median of six cycles per patient (range 1-14). Seven patients (13.5%) achieved a partial response and one a complete response (1.9%), for an overall intention-to-treat response rate of 15.4% (95% confidence interval 6.1% to 27.2%). The incidence of grade 3/4 toxicity was 23.1% for diarrhea, 21.2% for asthenia, 17.3% for neutropenia, 13.4% for emesis and 7.7% for infection. There were no treatment-related deaths. With a median follow-up of 20 months, median survival was 11.9 months and median time to progression was 4.6 months. CONCLUSIONS: CPT-11 plus raltitrexed is active in patients with 5-FU-refractory ACC, at the expense of moderate toxicity.

Adult↗

Cefepime monotherapy as an empirical initial treatment of patients with febrile neutropenia.

Currently, monotherapy is considered a valid alternative to the combination antibiotic treatments used for initial, empirical management of febrile neutropenia. The advent of new cephalosporins warrants assessment. The aim of this study was to prospectively evaluate the effectiveness of cefepime monotherapy in the treatment of cancer patients with febrile granulocytopenia (< 1000 leukocytes/muL and/or < 500 neutrophils/muL). A prospective, multicenter, nonrandomized trial was conducted. Initial treatment consisted of iv cefepime, 2 g every 8 h. If the patient was still febrile after 72 h, amikacin, vancomycin/teicoplanin, and amphotericin B were added sequentially. Response was evaluated according to EORTC criteria. One hundred twenty episodes were analyzed in 81 males and 39 females (median age, 52 yr; range, 15-83). The median leukocyte count at the time of diagnosis was 781 microL(-1) (range, 100-2600) and the median neutrophil count was 173 microL(-1) (range 0-500). The median duration of neutropenia (< 1000 neutrophils/microL) was 4.8 d (range, 3-20). Fifty-two episodes (44%) were confirmed microbiologically (42 presented as bacteremia), 31 with Gram-positive bacteria and 21 with Gram-negative bacteria, 47 (39.3%) were confirmed clinically, 16 (13.3%) were considered as probable infections, and 5 (4.2%) as doubtful infections. Protocol success was achieved in 110 episodes (91.7%), 8 (6.6%) were treatment failures, and 2 (1.7%) were not evaluable. Ninety-nine episodes (83.3%) were controlled with cefepime monotherapy, with 19 other episodes requiring additional antibiotics: amikacin in 7 (5.8%), amikacin + vancomycin/teicoplanin in 12 (10.1%). Three patients (2,5%) died during an episode of neutropenic fever. Cefepime is effective as an initial, empirical treatment of febrile neutropenia. The early addition of amikacin and/or vancomycin resolves most of the monotherapy failures, which seem somewhat lower than with other monotherapies.

Adolescent↗

Growth hormone treatment promotes guided bone regeneration in rat calvarial defects.

This study evaluated the biomechanical strength and bone formation in calvarial critical size bone defects covered with expanded polytetrafluoroethylene (e-PTFE) membranes in rats treated systemically with recombinant human growth hormone (rhGH). A full-thickness bone defect, 5 mm in diameter, was trephined in the central part of each parietal bone in 40 one-year-old female Wistar rats, which were randomly assigned to two groups of 20 animals each. The bone defects were covered with an exocranial and an endocranial e-PTFE membrane. From the day of operation, the rhGH-treated animals were given 2.7 mg rhGH/kg/day and the placebo-injected rats were given isotonic sodium chloride. The animals were killed 28 days after operation. The biomechanical test was performed by a punch out test procedure placing a 3.5-mm diameter steel punch in the centre of the right healed defect. After mechanical testing, the newly formed tissue inside the defect was removed and the dry and ash weights were measured. The left healed defects were used for three-dimensional (3D) reconstruction by means of micro-computer tomography (micro-CT). Ultimate load, ultimate stiffness, and energy absorption at ultimate load were significantly increased in the rhGH-treated group (P < 0.003). Also, tissue dry and ash weights were significantly augmented in the rhGH-treated group (P < 0.001). The 3D reconstruction of newly formed bone showed that there was almost twice as much bone volume present in the rhGH-treated defects compared with the placebo group. The experiment demonstrated that rhGH administration enhances bone deposition and mechanical strength of healing rat calvarial defects, covered with e-PTFE membranes.

Animals↗

Mandibular bone graft material for reconstruction of alveolar cleft defects: long-term results.

OBJECTIVE: To analyze the long-term effect of mandibular bone as donor material in bone grafting of the alveolar process defect in patients with unilateral cleft lip and palate (UCLP), compared with iliac crest cancellous bone. METHOD: During a 7-year period, 101 UCLP patients were bone grafted, 57 cases with iliac crest cancellous bone and 44 with mandibular symphyseal bone. The long-term results with an observation time of more than 4 years were analyzed with respect to marginal bone level and dental and gingival condition in the grafted area. Complications were recorded. RESULTS: The bone level in the grafted area was satisfactory in both groups. Impaction of cleft-side canines was found in 35% of the patients in both groups. Patients with agenesis of the cleft side lateral incisor had significantly more impacted canines, compared with patients with a cleft-side lateral situated in the lesser maxillary segment, probably due to the fact that the lateral incisors help in guiding the canine down through the grafted area. The number of complications was scarce, although both groups demonstrated some gingival retraction with a longer crown length at the cleft side central incisor. CONCLUSION: The findings of this study have changed our strategy in bone grafting. Timing of orthodontic treatment and bone grafting has been more varied depending on the position and presence of teeth in the cleft area. Bone grafting of the alveolar process is not just a local treatment of a bony defect, but in respect to the burden of treatment, bone grafting of the alveolar process has to be planned in accordance with orthodontic treatment and maxillofacial growth.

Alveolar Process↗

Clinical comparison between a resin-reinforced self-cured glass ionomer cement and a composite resin for direct bonding of orthodontic brackets. Part 2: Bonding on dry enamel and on enamel soaked with saliva.

The purposes of this investigation were to compare the clinical performance of a resin-reinforced self-cured glass ionomer cement to a standard composite resin in the direct bonding of orthodontic brackets when bonded onto: a) dry teeth and b) teeth soaked with saliva. The two bonding agents were compared using a split-mouth design. In that, both systems were used for direct bonding of stainless steel brackets in every patient. Thirty-eight consecutive patients with fixed appliances were followed for a period of 12 months. The patients were randomly divided into two groups: group A (11 patients) and group B (27 patients). In group A, the performance of 220 stainless steel brackets was evaluated: 110 brackets were bonded with GC Fuji Ortho glass ionomer cement (GC Industrial Co., Tokyo, Japan) onto dry teeth, and 110 bonded with System 1+ composite resin (Ormco Corp., Glendora, CA). In group B, the performance of 540 stainless steel brackets was evaluated: 270 brackets were bonded with GC Fuji Ortho onto teeth soaked with saliva, and 270 bonded with System 1+. In group A, GC Fuji Ortho recorded an overall failure rate (34.5%) significantly higher (p < 0.05) than System 1+ (9%) when applied onto completely dry teeth. Conversely, in group B, no statistically significant differences (p > 0.05) between the failure rates of the two bonding agents were found when GC Fuji Ortho was used on teeth soaked with saliva. It was concluded, therefore, that GC Fuji Ortho shows clinically acceptable bond strengths when bonded onto moist teeth, but not when used on dry enamel. Both bonding agents failed mostly at the enamel/adhesive interface, without causing any enamel damage.

Acrylic Resins↗

Importance of the critical-size bone defect in testing bone-regenerating materials.

A substantial interest exists in developing substitute materials and human recombinant bone-inducing factors to enhance bone regeneration both in the craniofacial complex and in other parts of the skeleton. A persistent problem has been to find an animal model that allows for the comparison of different osteopromotive materials. The purpose of this investigation was 1) to determine whether a 5-mm calvarial defect in adult rats fulfilled the requirements of a critical-size bone defect and 2) to discuss the use of this animal model in assessing bone repair in the craniofacial region. Bilateral full-thickness calvarial defects were trephined in the calvarial bone of 56 5- to 6-month-old Wistar rats. Except for minor amounts of bone formation limited to the margins of the defect, none of the defects revealed any signs of spontaneous bone regeneration 6 and 12 months after surgery. The full-thickness 5-mm calvarial defects thus fulfill the criteria for a critical-size bone defect. This animal model allows for an experiment with a paired design, it avoids inclusion of the sagittal suture in the osseous defect, and it thereby minimizes morbidity by reducing the risk of damaging the midsagittal sinus. An adequate experimental model has been developed to evaluate the efficiency of osteopromotive materials in the healing of bone defects in the craniomaxillofacial region.

Animals↗

Clinical comparison between a resin-reinforced self-cured glass ionomer cement and a composite resin for direct bonding of orthodontic brackets Part 1: Wetting with water.

The purpose of this study was to compare the clinical performance of a resin-reinforced self-cured glass ionomer cement to a standard composite resin in a split mouth design, by using both systems for direct bonding of orthodontic stainless steel brackets in every patient. Forty eight patients (34 females and 14 males, of which 29 were adults > 18 years of age) with fixed appliances were followed for a mean period of 10 months (range 4-16 months). The performance of 864 stainless steel brackets was evaluated: 404 brackets were bonded with GC Fuji Ortho glass ionomer cement (GC Industrial, Tokyo, Japan) onto teeth soaked with water, and 460 were bonded with System 1+ composite resin (Ormco, Glendora, CA). System 1+ recorded an overall failure rate (18.2%) significantly higher (p < 0.05) than GC Fuji Ortho (7.9%). There were no statistically significant differences (p > 0.05) between the failure rates in the upper and lower arches with either material. Both in the upper and lower arches, System 1+ exhibited a failure rate significantly higher (p < 0.05) than GC Fuji Ortho. When the bonding performance of the six anterior teeth was compared with first and second premolars, no statistically significant differences were found (p > 0.05) between bonding agents in either arch. System 1+ exhibited a failure rate significantly higher (p < 0.05) than GC Fuji Ortho, both in the anterior and posterior segments. Both bonding agents failed mainly at the enamel-adhesive interface, without causing any damage to the enamel.

Acrylic Resins↗

Constructing a Proton Titration Curve from Ion-Step Measurements, Applied to a Membrane with Adsorbed Protein

A new measuring method is described for obtaining a proton titration curve. The curve is obtained from a microporous composite membrane, consisting of polystyrene beads in an agarose matrix, with lysozyme molecules adsorbed to the bead surface. The membrane is incorporated into a sensor system by deposition on a silicon chip with a pH-sensitive ion-sensitive field effect transistor (ISFET) located in the middle of a Ag/AgCl electrode. The actual measurement is performed by creating a stepwise change in the salt concentration of the bathing electrolyte (the ion step) and measuring the ISFET potential versus the Ag/AgCl electrode. This potential shows a transient change in the ion step, which indicates a transient pH change in the membrane. This procedure is repeated at a series of pH values. Equations are presented to calculate the proton titration curve of the membrane from the amplitude and duration of the measured transients. Measurements show qualitative agreement between the curves obtained and equilibrium titration experiments on the same system.

Journal Article↗

[Analgesics in the postoperative period of abdominal interventions. The Study Group on Postoperative Analgesia of the Spanish Society of Clinical Pharmacology].

BACKGROUND: Analgesics can avoid postoperative pain. The aim of this study was to evaluate their prescription after abdominal surgery. PATIENTS AND METHODS: Prospective study including patients who had undergone abdominal surgery in two hospitals in Barcelona, in 1993. Prescription and administration of analgesic drugs, and pain severity during the first 48 hours of the postoperative period were evaluated. RESULTS: One hundred and sixty-four patients (83 men) were included. The most frequently prescribed drugs were metamizol (111; 68%), pethidine (83, 51%), and diclofenac (44; 27%). A high percentage of analgesic prescriptions on an "as needed" basis was recorded. Administered doses were lower than those recommended, and lower than those prescribed. Fifty-three percent of patients suffered significant pain during the first day. CONCLUSION: A too low proportion of analgesic drugs is prescribed in a predetermined schedule, in contrast to "as needed" prescription. Opiate derivatives are underused. All analgesic drugs are prescribed at inadequate dosage. This prescription pattern is associated with a high prevalence of postoperative pain.

Abdomen↗

Different approaches to anchorage: a survey and an evaluation.

Orthodontic treatment outcome is often compromised by the loss of anchorage. The forces acting on the anchorage unit have, however received surprisingly little attention, and the loss of anchorage is most frequently expressed in the sagittal occlusal relationship. The present paper discusses the interaction between vertical and sagittal components of dentofacial development, and the importance of taking vertical forces into consideration is stressed. The biological background for anchorage is reviewed, i.e., the impact on the cellular reaction of the periodontal ligament around the teeth of the anchorage unit from the orthodontic force system and from occlusion. A new rigid appliance consisting of two occlusal splints connected with transpalatal arches is introduced. The advantage of using the patient's sense of occlusion as part of anchorage by means of this appliance is demonstrated in a number of case presentations.

Adult↗

Recombinant transforming growth factor-beta1 induces endochondral bone in the baboon and synergizes with recombinant osteogenic protein-1 (bone morphogenetic protein-7) to initiate rapid bone formation.

Several members of the bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF-beta) families are molecular regulators of cartilage and bone regeneration, although their actual roles and combined interactions in skeletal repair are poorly understood. The presence of several molecular forms suggests multiple functions in vivo as well as synergistic interactions during both embryonic bone development and regeneration of cartilage and bone in postfetal life. Here we show for the first time that recombinant human transforming growth factor-beta1 (TGF-beta1) induces endochondral bone formation in extraskeletal sites of adult baboons. We also show that TGF-beta1 and recombinant human osteogenic protein-1 (OP-1, bone morphogenetic protein-7) synergize in inducing large ossicles in extraskeletal sites of the primate as early as 15 days after implantation. A single application of OP-1, in conjunction with an insoluble collagenous matrix as carrier (5, 25, and 125 microg/100 mg of carrier matrix) induced bone differentiation in the rectus abdominis of the baboon. This level of tissue induction was raised several-fold by the simultaneous addition of comparatively low doses of TGF-beta1 (0.5, 1.5, and 5 microg), which by itself induces bone formation in the rectus abdominis at doses of 5 microg/100 mg of carrier matrix. Combinations of OP-1 and TGF-beta1 yielded a 2- to 3-fold increase in cross-sectional area of the newly generated ossicles, with markedly elevated key parameters of bone formation, and corticalization of the newly formed bone by day 15, culminating in bone marrow generation by day 30. The tissue generated by the combined application of OP-1 and TGF-beta1 showed distinct morphological differences when compared with OP-1-treated specimens, with large zones of endochondral development and extensive bone marrow formation. At the doses tested, synergy was optimal at a ratio of 1:20 by weight of TGF-beta1 and OP-1, respectively. These results provide evidence for a novel function of TGF-beta1 in the primate and the scientific basis for synergistic molecular therapeutics for the rapid regeneration of cartilage and bone.

Animals↗

Comparison of the reliability of craniofacial anatomic landmarks based on cephalometric radiographs and three-dimensional CT scans.

OBJECTIVE: Conventional cephalometry is an inexpensive and well-established method for evaluating patients with dentofacial deformities. However, patients with major deformities, and in particular asymmetric cases are difficult to evaluate by conventional cephalometry. Both two- and three-dimensional computed tomography (CT) have been proposed to alleviate some of these difficulties. Only a few studies using metallic markers have indicated 3-D CT to be a useful diagnostic method, whereas no studies have evaluated the reliability of the anatomic cephalometric points used in 3-D CT. The aim of our study therefore was to compare the reliability of anatomic cephalometric points from conventional cephalograms and 3-D CT. METHODS: Nine human dry skulls were CT scanned. In addition standard lateral and frontal cephalograms were obtained. The CT scans were 3-D image reconstructed, and the cephalometric points were recorded as x, y, and z co-ordinates by two investigators. Computerized cephalometrics were performed-on the lateral and frontal cephalograms. Intra- and interindividual variations were calculated for each method and tested for statistical significance. RESULTS: Lateral cephalogram measures were more reliable than 3-D CT, with interobserver variations less than 1 mm for most points compared to about 2 mm for 3-D CT. Lateral cephalometrics also showed significantly less interobserver variation for six variables. This was, however, less obvious when 3-D CT was compared to frontal cephalograms. Frontal cephalometrics showed significantly less interobserver variation for three of the investigated variables. CONCLUSIONS: For standard lateral and frontal cephalometric points, there is no evidence that 3-D CT is more reliable than the conventional cephalometric methods in normal skull, and the benefit of 3-D CT cephalometric is indicated to be in the severe asymmetric craniofacial syndrome patients, as conventional cephalometrics is known to be inferior in these cases.

Adult↗

The nasal septum and the development of the midface. A longitudinal study of a pair of monozygotic twins.

The development of the nose and the growth of the midface has been followed in a pair of identical twins. One of them (twin A) had nasal septum destruction after septal haematoma and abscess at the age of 7 years, and was treated by immediate implantation of homologous septal cartilage from a tissue bank. From 7-17 years of age the growth and development of the nose and face were followed. Lateral cephalograms, photographs, acoustic rhinometry and rhinoscopy were performed. Twin B presented a normal nasal and facial growth and served as control. Twin A developed a saddle nose, an upward displacement of the anterior part of the maxilla, diminished vertical development of the nasal cavity, and a retrognathically positioned maxilla due to decreased anteroposterior maxillary growth. This case report seems to indicate that the cartilaginous nasal septum is an important factor influencing vertical and sagittal growth of the maxilla.

Abscess↗

Limited chondro-osteogenesis by recombinant human transforming growth factor-beta 1 in calvarial defects of adult baboons (Papio ursinus).

The therapeutic utility of a single application of recombinant human transforming growth factor-beta (hTGF-beta) has not been previously tested in large osseous wounds in primates. Sixteen calvarial defects, 25 mm in diameter, were prepared in four adult male baboons (Papio ursinus). In each animal, three defects were treated with increasing doses of hTGF-beta 1 in conjunction with baboon insoluble collagenous bone matrix as carrier (5, 30, and 100 micrograms of hTGF-beta 1/g of matrix). The fourth defect was implanted with collagenous matrix without hTGF-beta 1 as control. Serial undecalcified sections were prepared from the specimens harvested on day 30. Islands of cartilage and endochondral osteogenesis were found in hTGF-beta 1-treated defects, irrespective of the doses used. Histomorphometry of the defect site showed no significant differences between control and hTGF-beta 1-treated specimens with regard to bone and osteoid volumes. However, analysis of the regenerated tissue in proximity to the defect margins only showed that, on average, greater amounts of bone formed in specimens that were treated with 5 and 30 micrograms of hTGF-beta 1 when compared with controls. This suggests a possible effect on osteoblastic cells originating from the periosteal and endosteal spaces of the severed calvaria. Overall, however, this difference has no therapeutic implications for the healing of large cranial wounds in primates. The present findings indicate that a single application of hTGF-beta 1, in conjunction with collagenous matrix, results in limited chondro-osteogenesis in defects of membranous bone of adult baboons.

Analysis of Variance↗

Human recombinant transforming growth factor-beta 1 in healing of calvarial bone defects.

Bone healing plays an important role in orthognathic and craniofacial surgery. Bone tissue repair and regeneration are regulated by an array of growth and morphogenetic factors. Osteogenesis proceeds through a cascade of molecular and cellular events sequentially coordinated by members of both the bone morphogenetic protein and transforming growth factor-beta (TGF-beta) families. The efficacy of a single application of 2, 5, or 10 micrograms of recombinant human (rh) TGF-beta 1 to promote bone regeneration in 5-mm experimental calvarial defects of adult male rats was assessed histologically and histomorphometrically. The histomorphometric results of the experimental site were compared with those of the contralateral control side. Dosegroup comparisons were also performed. None of the control and experimental bone defects demonstrated complete bone closure. Limited bone regeneration was found close to the margins of the defects. A statistically significant difference in volume fraction composition (bone, osteoid, and soft tissue) was found between the 5- and 10-microgram rhTGF-beta 1-implanted and control defects. No difference was found in the 2-microgram rhTGF-beta 1-implanted group. The percentage of bone closure was statistically significantly higher in the 5-microgram rhTGF-beta 1-implanted group than in the control group. The present findings indicate that a single application of different doses of rhTGF-beta 1 does not promote clinically relevant osteogenesis in membranous calvarial bone defects in adult rats.

Animals↗