Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous vasopressin in non-resectable pancreas cancer.

BACKGROUND: Systemic palliative treatment with chemotherapy against advanced pancreas cancer has low effectiveness despite considerable toxicity. AIM: To investigate the safety, toxicity and tumour response of intraperitoneal 5-Fluorouracil (5-FU) with intravenous Leucovorin and to monitor 5-FU pharmacokinetics in plasma during intraperitoneal instillation with and without vasopressin in patients with non-resectable pancreas cancer. PATIENTS/METHODS: Between 1994 and 2003, 68 patients with non-resectable pancreas cancer TNM stage III and IV, were enrolled to receive intraperitoneal5-FU instillation 750-1500 mg/m2 and intravenous Leucovorin 100 mg/m2 for two days every third week. Tumour response, performance status and toxicity were recorded. Seventeen patients were also treated with intravenous vasopressin 0.1 IU/minute for 180 minutes, during intraperitoneal 5-FU instillation. Area under the curve (AUC) and peak concentration (Cmax) of 5-FU in plasma were analysed. RESULTS: The treatment was well tolerated with minor toxicity. One complete response (54.1+ months) and 2 partial responses were observed. Time to progression was 4.4 months (0.8-54.1+), and median survival was 8.0 months (0.8-54.1+). There was a significant reduction of 5-FU Cmax in plasma the second day of treatment if vasopressin was used (3.4+/-2.5 and 6.1+/-5.4 mumol/l, respectively, p<0.05). 5-FU AUC in plasma was not significantly affected by vasopressin either day of treatment. CONCLUSION: Intraperitoneal 5-FU is a safe treatment with low toxicity to patients with non-resectable pancreas cancer. Tumour response was 4.4% and median survival time 8.0 months. Addition of vasopressin did not significantly decrease plasma 5-FU AUC but reduced Cmax on day 2 of treatment.

Speech and other oral functions. Clinical and experimental studies with special reference to maxillary rehabilitation on osseointegrated implants.

The aims of this thesis were first to longitudinally investigate patients' opinions of their speech and other oral functions, evaluate some parameters of oral functions and speech production after treatment with a maxillary fixed prosthesis on osseointegrated implants (FPOI) and secondly to analyse normal Swedish [s] production. 21 consecutive selected patients rehabilitated with maxillary FPOI were studied over a 3-year period. The parameters of masticatory functions were clenching force, chewing efficiency, oral stereognosis and oral motor ability. With the aid of perceptual, acoustic, and model analysis the speech production with special reference to [s] was also longitudinally evaluated. The occlusal thickness perception (OTP) was estimated. In order to evaluate the usefulness of electropalatographic (EPG) and optoelectronic equipments in analysing speech production a multiple analysis of [s] production in varying contexts were made at four sessions. All subjects were very pleased with the oral rehabilitation. The chewing efficiency over time improved. The replacement of a complete denture with an FPOI in the upper jaw, resulted in to a progressive increase of chewing efficiency and clenching force, and a subjective improvement of oral function. Concerning OTP, a threshold level of 20 microns was recorded in the subjects with natural dentition, at 50 microns in FPOI subjects and 100 microns subjects with complete dentures. Time for identification of small test pieces as an expression of oral stereognostic ability (OSA) as well as number of errors decreased immediately after insertion of an FPOI compared to the edentulous condition. Assembly time in oral motor ability test (OMA) also decreased. A further improvement was found at the final examination 3-6 months after rehabilitation. After initial phonetic problems, 92% of the patients considered themselves free from speech problems at the 3 year follow-up. The patients' experience corresponded well with the judgements of both the expert and the non expert groups. Difficulties in pronouncing [s] were associated with decreased bite-force, number of occluding contacts, frontal width of the fixed prosthesis and tenderness at palpation of the masticatory muscles. No correlation between open or closed interdental spaces and deteriorated speech was found. In general, EPG and mandibular movement pattern were similar between sessions and the sound quality normal. However, when subjects wore the artificial palate for the first time the [s] groove was wide, the mandibular movement smaller and the [s] quality some what deteriorated. [s] in varying context had different tongue groove width but a similar high average mandibular position.

Oral function in patients wearing fixed prosthesis on osseointegrated implants in the maxilla: 3-year follow-up study.

Seventeen consecutive selected patients rehabilitated by means of a full maxillary bridge on osseointegrated implants ad modern Brånemark were evaluated over a 3-yr period. Besides a subjective evaluation by means of a questionnaire an examination of the occlusal relationship, chewing force, chewing efficiency and interocclusal threshold level was performed before, immediately after, 3-6 months after, and finally 3 yr after bridge installation. All subjects were very pleased with the oral rehabilitation. The chewing force and the chewing efficiency development increased over time, while the threshold level for interocclusal detection remained unchanged. The clinical dysfunction index according to Helkimo indicated that there was no marked change in signs of dysfunction of the patients' masticatory systems during the observation period. From the present longitudinal investigation one can conclude that the replacement of a full maxillary denture with a fixed prosthesis on osseointegrated implants, facing a natural dentition or an osseointegrated implant supported bridge in the opposite jaw, leads to a progressive increase of chewing efficiency and chewing force, and a constant subjective improvement of jaw function, while no masticatory dysfunction seems to occur during the observation period.

Occlusal perception of thickness in patients with bridges on osseointegrated oral implants.

Perception of thickness was estimated in subjects with osseointegrated oral implant bridges (OIB), complete denture wearers and subjects with complete natural dentitions. The test was performed with factory-produced aluminum foil, 9, 20, 50, 100 and 150 micrometers thick, in the regions of the right second premolars, the canines and the central incisors. Occlusal perception did not differ between the three regions in any of the groups. Certain perceptiveness (greater than 80% of tests correct) was found at the 20 micrometers level in subjects with natural dentitions, at the 50 micrometers level in OIB subjects and at the 100 micrometers level in subjects with a complete denture in one or both jaws. It is concluded that partial or complete lack of periodontal receptors is compensated for by other perceptive organs and that implant bridge therapy ad modum Brånemark partly restores occlusal sensibility.

Oral function in patients wearing fixed prosthesis on osseointegrated implants in the maxilla.

Bite force, chewing efficiency and tactile sensibility were investigated in 21 subjects with OIB (Osseointegrated Implant bridges) in the maxilla or in both jaws. Recordings were performed before treatment, approximately 1 wk and finally 3-6 months after treatment. The bite force was recorded in the incisor, canine, and premolar areas and was tested at gentle biting, biting as when chewing, and maximal biting. In the chewing tests the chewing time, the chewing velocity, the time to swallowing, and the Ci (Chewing Efficiency Index) were calculated. The occlusal thickness perception was tested in the front with a 12.8 x 10(-3) mm thick plastic foil. The maximal bite force was more than doubled, the Ci improved about one index unit, and the occlusal thickness perception improved from on average 57.5 x 10(-3) mm to 18.7 x 10(-3) mm during the observation time. It is concluded that treatment with upper OIB has a very positive impact on oral function as reflected by improved bite force, chewing efficiency, and occlusal thickness perception.

Speech in connection with maxillary fixed prostheses on osseointegrated implants: a three-year follow-up study.

In 21 individuals, edentulous in the upper jaw, the speech function was evaluated. In an earlier study, registrations were made when the patients wore complete dentures in the upper jaw and 3-6 months after they had been treated with fixed prostheses on osseointegrated implants in the maxilla. These patients were re-examined after 3 years, as reported in this follow-up study. An expert group as well as a non-expert group participated in a perceptual analysis. Acoustic, audiological and cast analyses were performed. In addition, a questionnaire was filled in. The results indicated that, after initial phonetic problems, 94% of the individuals considered themselves free from speech problems at the 3-year follow-up. The patients' experience of the change of the s-sound corresponded well with the judgement of both the expert and the non-expert groups. Difficulties with pronouncing the s-sound were associated with decreased bite force, the number of occluding contacts, the frontal width of the fixed prosthesis and tenderness at palpation of the masticatory muscles. These oral functional factors will contribute to the s-sound production.

Maxillary fixed prostheses on osseointegrated dental implants.

The clinical and technical procedures used in the production of a fixed prosthesis on osseointegrated implants in the edentulous maxillae were described. The subjective evaluation and some clinical recordings in 21 treated patients were reported. Initial results were very favorable.

Measurements of pressure-broadening coefficients of NO and O3 using a computerized tunable diode laser spectrometer.

Foreign-gas broadening coefficients have been measured for selected lines of ozone in the 9.2-microm region and for several R -branch lines of nitric oxide in the 5.4-microm region using a computerized tunable diode laser spectrometer. The data analysis showed the importance of fitting a Lorentzian line shape out to several times the halfwidth to obtain a correct value of the broadening coefficient. The measured broadening coefficients of nitric oxide were in good agreement with those obtained by Abels and Shaw. The results of the analysis of eleven lines in the nu(1) band and five lines in the nu(3) band of ozone show a transition-dependent broadening coefficient. The average value of the foreign-gas broadening coefficients for the measured nu(1) and nu(3) lines are 0.075 and 0.073 cm(-1) atm(-1), respectively.

Experimental studies comparing iohexol and 51Cr-EDTA for glomerular filtration rate measurements.

The total plasma clearance as well as the renal clearance of iohexol were evaluated for determination of the glomerular filtration rate (GFR) in 16 anesthetized pigs. The iohexol levels in urine and plasma were measured by X-ray fluorescence. The total plasma clearance of 1 and 4 ml/kg b.w. of iohexol 300 mg I/ml was compared to the simultaneously as well as nonsimultaneously calculated total plasma clearance of 51Cr-EDTA. The total plasma clearance of 51Cr-EDTA and of iohexol turned out to be equal and independent of the injected dose of iohexol. The injected dose did not have any effect on the renal clearance of iohexol either. It is concluded that iohexol and 51Cr-EDTA are similar as marker substances for determination of the GFR.

Simultaneous urography and determination of glomerular filtration rate. A comparison of total plasma clearances of iohexol and 51Cr-EDTA in plegic patients.

The total plasma clearance of iohexol at urography and 51Cr-EDTA was compared in 31 patients with di- or tetraparesis. A reference 51Cr-EDTA clearance was also performed 24 hours prior to the urography. The GFR was calculated from one, 2 or 4 plasma samples collected 180, 210, 240 and 270 min after the injection. An X-ray fluorescence analyzer was used for the analysis of iohexol in plasma as well as the contrast medium clearance calculations. It was shown that single or multiple sample clearance of iohexol and 51Cr-EDTA were equivalent methods for measurement of the GFR. The GFR was not affected by iohexol in a dose routinely used for urography. It was concluded that the patient comfort is improved if 51Cr-EDTA clearance is replaced by contrast medium clearance in association with urography.

Speech before and after treatment with bridges on osseointegrated implants in the edentulous upper jaw.

Speech may be affected by the transition from complete dentures to fixed prosthesis on osseointegrated implants (OIB). If so, is there any correlation between interdental spaces (open or closed) in the prosthodontic construction and deteriorated speech? 21 individuals advocated for maxillary OIB were randomised so that one half of the group got constructions with wide interdental spaces and the other half with minimised interdental spaces. All patients were examined audiologically and their speech was individually tape-recorded before and after treatment. Perceptual, acoustic, model and audiological analyses were made. Approximately 60% of the patients were judged to have indistinct speech after the treatment. The s-sound was perceptually and acoustically distorted. 67% of the patients suffered from hearing defects. No correlation between interdental spaces (open or closed) and deteriorated speech could be found. It is supposed, that hearing plays a part in the effort to adjust speech to a new maxillary OIB, and thus reduced hearing can enhance speech difficulties.

An electropalatographic and optoelectronic analysis of Swedish [s] production.

The objective of this study was to evaluate the usefulness of electropalatography (EPG) as a method for diagnostic analysis of the [s] sound and also to make a multiple analysis of the production of the normal Swedish [s] sound in various contexts. Eleven dental students participated. EPG registration, optoelectronic recording of jaw movements, and acoustic registration of a test phrase were made simultaneously. A speech perceptual test was also made. There were four separate recording sessions. Except for at session I, subjects wore an EPG palate. At session II they were not adapted to it, in contrast to the later occasions. The EPG appeared to be a valid method for investigating the [s] sound. In general, EPG and mandibular movement patterns were similar between sessions, and the sound quality normal throughout. At session II, however, the tongue groove was wider, the mandibular movements smaller, and the [s] quality somewhat deteriorated. [s] in various contexts had different tongue groove widths but similar high average mandibular position. To prevent speech and especially [s] sound problems when constructing prosthetic devices, it is important to advance our knowledge of [s] sound production.

Beyond the One-Electron Approximation: Density of States for Interacting Electrons.

The concept "density of states" can be given many different meanings when we go beyond the one-electron approximation. In this survey we concentrate on the definition tied to excitation processes, where one electron is added or removed from the solid. We discuss the one-particle spectral function for conduction and core electrons in metals, how it can be approximately calculated, and how it can be related to different types of experiments like x-ray photoemission, x-ray emission and absorption, photoemission and optical absorption in the ultraviolet, and the Compton effect. We also discuss the form of the exchange-correlation potential for use in band structure calculations.

Occlusal wear. A follow-up study of 18 subjects with extensively worn dentitions.

Eighteen patients with moderate to severe dental wear were re-examined 6-10 years after a treatment period that included use of occlusal splints at night. The splints were used with various intensities for an average of 2 years. The methods of evaluation comprised a questionnaire, clinical examination, comparison of dental casts, salivary analysis, and bite force measurements. The changes in dental wear during the follow-up period were small, the typical finding being an increase of facets but no measurable reduction of tooth length. The results indicate that many variables apart from occlusal parafunctions, such as acid regurgitation and salivary and dietary factors, may contribute to loss of tooth substance diagnosed as dental wear. In most patients, the continuing wear process was slow after long-term treatment with occlusal splints.

Differential reflectance of natural and man-made materials at CO(2) laser wavelengths.

The differential reflectance of several naturally occurring and man-made materials at CO(2) laser wavelengths is determined. The computer-controlled measurement system has two CO(2) lasers and determines the differential reflectance of each material by measuring the ratio of the reflected signals at two wavelengths simultaneously. These results can be used to improve the accuracy of air pollution measurement systems which derive their return signals from topographic targets.

Air pollution monitoring with a Q-switched CO(2)-laser lidar using heterodyne detection.

A differential absorption lidar (DIAL) using a Q-switched CO(2) laser and a heterodyne receiver has been developed. The DIAL system is highly automated with computer-controlled laser-line selection and signal processing. The transmitter operates at a pulse-repetition frequency of 20 kHz and has an average output power of 1.8 W. A wideband HgCdTe detector is used together with a high speed adding buffer to detect the return signals. The system has been used in a field experiment to monitor ethylene emission from a petrochemical factory.

Iohexol clearance for renal function measurement in gynaecologic cancer patients.

PURPOSE: To determine a valid and practical routine for glomerular filtration rate measurement in gynaecologic cancer patients. MATERIAL AND METHODS: The established method, endogenous creatinine clearance, was compared to 51Cr-EDTA clearance and contrast medium clearance in 68 women with various gynaecologic carcinomas. Contrast medium clearance was determined in association with conventional urography (iohexal 300 mg I/ml, 40 ml) for evaluation of urinary tract involvement by the tumour. Automated X-ray fluorescence analysis equipment was used for the plasma analysis of iohexol and clearance calculations. Endogenous creatinine clearance and 51Cr-EDTA clearance were determined according to standard routine procedures. Simultaneous determinations of contrast medium clearance and 51Cr-EDTA clearance (n = 33), contrast medium clearance and endogenous creatinine clearance (n = 50), as well as 51Cr-EDTA clearance and endogenous creatinine clearance (n = 30) were compared. RESULTS AND CONCLUSION: The mean differences were -2.8 (SD 6.6), -1.8 (SD 22.3), and 2.7 (SD 18.3) ml/min/1.73 m2, respectively. It is concluded that contrast medium clearance is as adequate as 51Cr-EDTA clearance for glomerular filtration rate measurement. We suggest that contrast medium clearance should replace endogenous creatinine clearance, especially in patients referred for urography.

Evaluation of single sample clearance calculations in 902 patients. A comparison of multiple and single sample techniques.

PURPOSE: To derive new formulae for the calculation of single sample clearance of the contrast medium iohexol and to compare the formulae to a selection of existing single sample clearance formulae derived for the calculation of 51Cr-EDTA and 99mTc-DTPA clearance. MATERIAL AND METHODS: Glomerular filtration rate (GFR) was calculated from total plasma clearance of iohexol used for urography in 902 patients. Two plasma samples were drawn in each patient. Automated x-ray fluorescence analysis equipment was used for the plasma iodine analysis. Single and multiple sample iohexol clearance values were compared. In 77 patients the multiple sample clearance values were additionally compared to a 51Cr-EDTA clearance performed simultaneously or within 14 days. RESULTS: The precision of the results calculated by the existing single sample clearance formulae and the derived iohexol single sample clearance formulae were essentially the same. The most precise of the derived formulae was that based on the Bak Christensen & Groth formula. The correlation between multiple sample clearance of iohexol and 51Cr-EDTA was high (r = 0.918). CONCLUSION: Iohexol can substitute 51Cr-EDTA for GFR measurement. A valid GFR can be calculated from a single plasma sample determination of iohexol clearance using either the existing formulae or the new formulae derived from the present study.