Biomedical subjects
Publications and source records attributed to A Kramer.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A bacterially expressed single chain antibody (scFv215) directed against the largest subunit of drosophila RNA polymerase II was analysed. Structure and function of the antigen binding site in scFv215 were probed by chain shuffling and by site-specific mutagenesis. The entire variable region of either the heavy or light chain was replaced by an unrelated heavy or light chain. Both replacements resulted in a total loss of binding activity suggesting that the antigen binding site is contributed by both chains. The functional contributions of each complementarity determining region (CDR) were investigated by site specific mutagenesis of each CDR separately. Mutations in two of the CDRs, CDR1 of light chain and CDR2 of heavy chain, reduced the binding activity significantly. Each of the amino acids in these two CDRs was replaced individually by alanine (alanine walking). Seven amino acid substitutions in the two CDRs were found to reduce the binding activity by more than 50%. The data support a computer model of scFv215 which fits an epitope model based on a mutational analysis of the epitope suggesting an alpha-helical structure for the main contact area.
Standard treatment of locally advanced laryngeal, hypopharyngeal, and some oropharyngeal cancers includes total laryngectomy. In an attempt to preserve the larynx through induction chemotherapy, we conducted two consecutive phase II studies. From March 1986 to February 1991, 64 patients with advanced untreated but resectable head and neck cancer who would require total laryngectomy were enrolled on one of two cisplatin-based induction regimens: cisplatin-bleomycin-5-fluorouracil (PBF) in 31 patients and cisplatin-5-fluorouracil (PF) in 33; all received definitive radiotherapy. Surgery was reserved for patients who achieved less than a partial response to chemotherapy and patients with residual or recurrent disease after sequential chemotherapy plus radiotherapy. Overall complete plus partial response rates to both cisplatin-based regimens were comparable. The combined PF and PBF overall response rates were 75% for laryngeal cancer, 78% for hypopharyngeal cancer, and 75% for oropharyngeal cancer. Complete response rates after radiotherapy were 88%, 83%, and 50%, respectively. Neutropenia (< 1,000 cells/mm3) was the most common hematologic toxic effect: it occurred in 44% of patients who received PF and 16% of those who received PBF. Grade > or = 3 mucositis occurred in 50% of patients who received PF and 4% who received PBF. The data suggest that laryngeal preservation was feasible in all three primary-site subgroups. With follow-up of 15+ to 54+ months, 44% of patients with laryngeal cancer, 28% with hypopharyngeal cancer, and 22% with oropharyngeal cancer are alive with laryngeal preservation. The overall 2-year survival rates for patients with cancer of the larynx, hypopharynx, and oropharynx were 71%, 46%, and 38%, respectively.
In a randomized clinical study, 61 hospitalized men were examined to test the local tolerability and antimicrobial efficacy of antiseptic treatment of the genitals with povidone iodine versus octenidine hydrochloride solution. Antibacterial efficacy was established by comparing the total aerobic bacterial colony count from standardized swabs from the orificium urethrae externum before, immediately after, and 30 and 60 min after antisepsis. Tolerability was assessed by dermatoscopy, applying a scale to rate the criteria of reddening, erosions and microbleeding. pH-value was taken and the nitracin yellow test carried out at several intervals. Patients assessed sensations (itching, burning, warmth, cold tension) in visual analogue scales. The test for equivalence in efficacy of both antiseptic agents produced no significant result (P = 0.3). The sum score of tolerability produced a better result for povidone iodine. In addition, the drop in the pH value after observed antisepsis with povidone iodine provides an additional protective mechanism against bacterial colonization.
BACKGROUND: The aim of the study was to assess the integrity of non-sterile latex gloves (Biogel Diagnostic (A), Biogel Dental (B), Gentle Skin (C) and Manufix (D)) in clinical dental practice. MATERIALS AND METHODS: After use, the gloves were collected and examined for perforations using the water inflation test according to the EN 455-1 Standard. Over a 12-month period 847 used gloves were collected and assessed. The mean duration of use for gloves A/B/C/D was 175/112/78/79 min respectively. In spite of these differences favoring gloves C and D, 16% of glove A, 14% of glove B, 21% of glove C and 29% of glove D were found to leak. The proportion of perforated gloves increased slightly if a hygienic handrub using an alcoholic hand disinfectant had been carried out immediately prior to gloving. CONCLUSION: The results indicate striking differences between the quality of medical gloves. As all the gloves comply with the European regulations in terms of integrity, it is very difficult for the user to distinguish between gloves of superior or inferior quality. In a clinical setting it is therefore recommended that the appropriate glove should be determined for each situation. Hands must be thoroughly dry if they are disinfected prior to gloving, since hands still wet with alcoholic disinfectant may increase the risk of glove perforation.
HYPOTHESIS: Advanced airway intervention techniques are being considered for use by basic emergency medical technicians (EMTs). It was hypothesized that basic EMTs would be able to discriminate reliably between intratracheal and esophageal endotracheal tube placement in a mannequin model. DESIGN: An airway mannequin with a closed chest cavity was intubated randomly either esophageally or tracheally, and the cuff was inflated. A stethoscope, bag ventilator, and laryngoscope were available next to the mannequin. Placement was assessed by auscultation or direct visualization at the discretion of the EMT. A blinded investigator graded the student. SETTING: A classroom in a large, urban medical center. PARTICIPANTS: Subjects were basic EMTs who volunteered to take part after the conclusion of a six-hour endotracheal intubation training course. RESULTS: Thirty-three subjects were tested. Seventeen of 18 (94%) tracheal intubations and 11 of 15 (73%) esophageal intubations were identified correctly. Only 72% of the students listened to the epigastrium, 81% listened to the lungs, and 85% attempted ventilation. The 10 students who visualized the cords discovered all five esophageal intubations. The 23 students who did not visualize the cords missed four and found six esophageal intubations. CONCLUSION: Basic EMTs had difficulty assessing endotracheal tube placement in a mannequin model. The 27% miss rate for identifying esophageal intubations suggests that basic EMTs will require additional training for safe field use of any airway that requires assessment of tube placement.
The pentadentate H3bhci [1,3,5-trideoxy-1, 3-bis((2-hydroxybenzyl)amino)-cis-inositol] and its bifunctionalized analogue H3bhci-glu-H [1,3,5-trideoxy-1, 3-bis((2-hydroxybenzyl)amino)-5-glutaramido-cis-inositol] were synthesized, and their coordination chemistry was investigated with inactive rhenium, with no carrier added Re-188 and with carrier added Re-186. The neutral Re(V) complexes [ReO(bhci)] and [ReO(bhci-glu-H)] are formed in good yields starting from [ReOCl3(P(C6H5)3)2] or in quantitative yield directly from [186/188ReO4]- in aqueous solution by reduction with Sn(II) or Sn(0). The X-ray structures of [ReO(bhci)] and [ReO(bhci-glu-H)] were elucidated revealing pentadentate "side on" coordination of the ligands to the "Re=O" core. The basic cyclohexane frame adopts a chair form in the case of [ReO(bhci)] and a twisted boat form in the case of [ReO(bhci-glu-H)]. [ReO(bhci)] crystallizes in the monoclinic space group C2/c with a = 27.425(3), b = 14.185(1), c = 19.047(2) A, and beta = 103.64(2) degrees and [ReO(bhci-glu-H)] in the monoclinic space group P21/c with a = 13.056(3), b = 10.180(1), c = 22.378(5) A, and beta = 98.205(9) degrees. Both 188Re complexes are stable in human serum for at least 3 days without decomposition. After injection into mice, [ReO(bhci-glu)]- is readily excreted through the intestines, while [ReO(bhci)] is excreted by intestines, liver, and the kidneys. TLC investigations of the urine showed exclusively the complexes [ReO(bhci-glu-H)] and [ReO(bhci)], respectively, and no decomposition products. For derivatization of antibodies, the carboxylic group of [ReO(bhci-glu-H)] was activated with N-hydroxysuccinimide, which required unusually vigorous reaction conditions (heating). The anti colon cancer antibody mAb-35 [IgG and F(ab')2 fragment] was labeled with [186/188ReO(bhci-glu)] to a specific activity of up to 1.5 mCi/mg (55 MBq/mg) with full retention of immunoreactivity. Labeling yields followed pseudo-first-order kinetics in antibody concentration with the ratio of rates between aminolysis and hydrolysis being about 2. Biodistributions of 186Re-labeled intact mAb-35 as well as of its F(ab')2 fragment in tumor-bearing nude mice revealed good uptake by the tumor with only low accumulation of radioactivity in normal tissue.
OBJECTIVE: The internal thoracic artery (ITA) is the most important graft in coronary artery bypass grafting. Its distal region is, however, prone to vasospasm. We studied the effects of nitroglycerin (NTG) and isosorbide-dinitrate (DSDN) on distal segments of left versus right ITA. METHODS: Rings of distal segments (6 to 9 mm proximal to bifurcation) of the human left and right ITA were studied. After baseline contraction of the rings, achieved using 60 mmol/L of KCl, they were exposed to increasing doses of ISDN and NTG (10 to 100 microg/ml), and dose-response curves were recorded. RESULTS: The contractile response of left ITA rings to KCl were significantly lower than those of right ITA rings (1.87 +/- 0.25 g versus 3.5 +/- 0.61 g, p < 0.005). Both nitrates inhibited the contractile response in a concentration-dependent manner, with relaxing effects of ISDN higher than those of NTG (p < 0.01) in both left and right ITA rings. CONCLUSIONS: The distal segment of the left ITA is less prone to vasospasm than that of the right. ISDN has a considerably higher relaxant effect on this segment than NTG. We therefore recommend favoring high doses of ISDN over NTG as an antispastic measure.
PURPOSE: Osteoporosis reveals a higher risk of fractures. Due to the lack of possibilities to anchor fixation elements, fracture treatment often turns out to be complicated. An experimental study served to investigate the extent to which the application of bone cement through a modified gliding screw (Dynamic Hip Screw DHS) would improve the screw anchoring in osteoporotic femoral heads. METHODS: Quasi-static compressive and torsional load tests were used to assess the desired improvement of the screw anchoring. Cadaver femur pairs served to compare the cement augmentation to the uncemented contralateral control. RESULTS: The improvement of the holding strength of the screw under static compressive and torsional load depended on the cement flow into the adjacent bone tissue. The filling with additional cement was only successful after having created a small hollow space at the screw tip with a special instrument. Consequently, under compression as well as torsion, the cement application yielded improvements from 17% up to several times as much. CONCLUSION: In the application of gliding screws in osteoporotic femoral heads, the locally limited cement application through the implant has been shown to be a biomechanical possibility to improve screw fixation.
An evaluation of Technology Resources Inc. (TRI) Amphetamine, Barbiturate, Narcotic (G) and Narcotic (S) "Dipsticks" for drugs of abuse in urine was made. The results obtained by six individuals reading the "Dipstick" papers was compared with the analysis of the same urine samples, by a combination of TLC, EMIT, RIA and GLC. The data obtained with "Dipstick" papers, regardless of the drug tested, were clearly unreliable (high percentage of false negatives, low percentage of true positives) and the assay was unsuitable as a technique for screening urines for drugs of abuse.
The main target of the combination of octenidine with phenoxyethanol (Octenisept) is the antisepsis of acute wounds, whereas polyhexanide combined with polyethylene glycol in Ringer solution (Lavasept) is the agent of choice for antisepsis of chronic wounds and burns. Because comparative data for both agents on the effects on wound healing are lacking, we investigated the influence of preparations based on polyhexanide and octenidine versus placebo (Ringer solution) in experimental superficial aseptic skin wounds (n = 108) of 20 mm diameter, using a double-blind, randomised, stratified, controlled, parallel-group design in piglets. Computerised planimetry and histopathological methods were used for the assessment of wound healing. Histologically, no significant differences could be verified at any time between the 3 groups. However, in the early phase (day 9 after wounding), the octenidine-based product retarded wound contraction to a significantly greater extent than placebo and polyhexanide, whereas in the later phase (days 18 and 28), polyhexanide promoted contraction significantly more than did placebo and octenidine. The consequence is complete wound closure after 22.9 days using polyhexanide, in comparison to the placebo after 24.1 days (p < 0.05) and octenidine after 28.3 days (no statistical difference to placebo). This may be explained by the better tolerance of polyhexanide in vitro, which was demonstrated with dose and time dependence in cytotoxicity tests on human amnion cells.
Knee flexion deformity has an adverse effect on stride length and cadence, resulting in an inefficient and often uncomfortable gait. The purpose of this study was to introduce anterior stapling of the distal femur as a method to treat mild to moderate fixed flexion deformity of the knee. The authors undertook stapling in 28 patients (47 knees) with flexion deformities resulting from a variety of underlying conditions, including spina bifida, cerebral palsy, SCIWORA, and skeletal dysplasia. The preoperative clinical evaluation included assessment of hamstring contracture, fixed knee flexion deformity, and gait pattern. The technique is minimally invasive, requires no immobilization, and allows immediate resumption of bracing and physical therapy as needed. Preoperative fixed flexion deformities were typically 10 degrees -25 degrees (maximum 45 degrees ), decreasing to 0 degrees -11 degrees after surgery. Except for one patient who extruded a staple within the first postoperative month, there were no complications. The authors conclude that stapling is well tolerated and provides an excellent alternative to osteotomy in the immature patient by allowing gradual correction of fixed flexion deformities via growth manipulation.
Besides mites, filamentous fungi and yeasts play an important role as domestic allergens. Among different allergen avoidance strategies the efficacy of synthetic mattress encasings has been demonstrated for the reduction of house dust mites. Whether these synthetic encasings are also able to reduce the growth of fungi on the mattress under domestic conditions has not been assessed so far. To determine if the fungal growth on mattresses can be reduced by the use of synthetic encasings we assessed the fungal colonisation of mattresses covered either by conventional cotton encasings or by polyurethane encasings impermeable to particles > 3 mum. Within a 12-month period dust samples were obtained from the mattresses. Fungal quantities were measured by counting colonies on agar plates incubated at 20 degrees C and 37 degrees C. The counts of fungi were significantly higher on mattresses with cotton encasings. Penicillium spp. and Aspergillus spp. were isolated most frequently. Therefore the application of synthetic encasings with similar properties to the encasings used in this investigation is recommended as part of an allergen avoidance strategy for patients sensitised to fungal allergens.
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