INTERRELATION BETWEEN ACTIVATION AND POLYMERIZATION IN GRAMICIDIN S BIOSYNTHESIS

The nucleic acid-independent biosynthesis of the peptide antibiotic gramicidin S results from the interaction of an enzyme bearing phenylalanine in activated form with a polyenzyme system charged with the other four component amino acids.After reaction with ATP, magnesium, and any or all of its amino acid substrates, the polyenzyme system (mol wt 280,000) yields complexes containing AMP and the respective amino acids in the proportion of 1 to 2. Similar complexes are formed by another enzyme (mol wt 100,000) on incubation with ATP, magnesium, and L- or D-phenylalanine. The amino acids are probably bound as aminoacyl adenylates and then transferred to another function on the enzyme. Initiation of polymerization is achieved by combination of the two complexes. No ATP is needed for completion of synthesis, and free intermediates are not released. Enzyme organization and specificity are responsible for the ordering of the amino acid sequence.     

Portrayal of pheochromocytoma and normal human adrenal medulla by m-[123I]iodobenzylguanidine: concise communication

The radiopharmaceutical m-[131I]iodobenzylguanidine (I-131 MIBG), which is readily taken up by adrenergic vesicles, produces scintigraphic images of pheochromocytomas in man but rarely visualizes normal adrenal glands. Iodine-123 has many potential advantages over I-131 as a radiolabel for MIBG, including shorter half-life, freedom from beta emissions, and increased gamma-camera efficiency. In this study, diagnostic doses of MIBG labeled with I-131 and I-123, with nearly equivalent radiation dosimetry, were compared as imaging agents in eight patients with known or suspected pheochromocytoma. Images of superior quality were obtained with I-123 MIBG, and lesions not visualized using I-131 MIBG were portrayed. In addition, the normal adrenal medullae were visualized on the I-123 MIBG scintigrams in six out of eight patients.     

The Sepulveda VA Geriatric Evaluation Unit: data on four-year outcomes and predictors of improved patient outcomes

Data from its first four operating years indicate that the Sepulveda VA Geriatric Evaluation Unit is having consistent beneficial effects on patient care. These benefits include improved diagnostic accuracy, reduced use of drugs, improved functional status, and improved placement location. However, not all patients benefit equally, and differences between patient responses highlight the need to select those who will benefit most from relatively costly Geriatric Evaluation Unit services. Discriminant and regression analyses were performed on 98 consecutive patients to determine which patients admitted to the Geriatric Evaluation Unit would show greatest improvement in terms of placement, functional status, one-year survival, and living location, and which patients would be treated most efficiently in terms of length of stay. Patient characteristics on admission significantly associated with discharge home included a relatively high functional and cognitive status, the absence of an unstable medical problem, and not being expected to need nursing home placement by the referring physician. The latter two factors alone predicted actual placement location on the next 101 patients admitted to the Geriatric Evaluation Unit with high predictive accuracy (88.5 per cent). Factors predictive of patients whose functional status would improve on the Geriatric Evaluation Unit included absence of an unstable medical problem and being over 75 years old (predictive accuracy was 82.5 per cent). Two major factors associated with long patient stays on the Geriatric Evaluation Unit were low functional status scores and not living in own home or with family. These analyses indicate criteria that may be useful in selecting patients for inpatient geriatric evaluation and rehabilitation programs.     

Imiquimod leads to a decrease of human papillomavirus DNA and to a sustained clearance of anal intraepithelial neoplasia in HIV-infected men

Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated precursor lesion of anal carcinoma, is highly prevalent in HIV-infected men having sex with men (MSM). This prospective follow-up study evaluated the long-term results of imiquimod treatment of AIN in 19 HIV-infected MSM. Standardized follow-up examinations included high-resolution anoscopy, anal cytology/histology, HPV typing, and DNA load determination for HPV types 16, 18, 31, and 33. Mean follow-up time was 30.3 months. A total of 74% (14/19) of the patients remained free of AIN at the previously treated site. Five patients (26%) had recurrent high-grade AIN after a mean time of 24.6 months. At the end of follow-up, the numbers of HPV types as well as high-risk HPV-DNA loads were significantly lower than before therapy. During follow-up, 58% of all patients (11/19) developed new anal cytological abnormalities in previously normal, untreated anal regions. 55% of these new AIN lesions were high-grade lesions and most of them were located intra-anally and associated with high-risk HPV types not detectable before therapy. These results demonstrate that imiquimod leads to a high rate of long-term clearance of AIN in HIV-positive men together with a prolonged decrease of high-risk HPV-DNA load. However, new AIN lesions associated with previously undetected HPV types frequently occur in untreated areas.     

Conformations of the li-antamanide complex and na-[phe, val]antamanide complex in the crystalline state

Antamanide, a cyclic decapeptide isolated from the poisonous mushroom Amanita phalloides, preferably complexes with Na⁺, but in less polar solvents, e.g., acetonitrile, also with Li⁺ or K⁺. The selectivity of complexation makes it an important model for the study of conformational requirements of ion binding. The conformations of the lithium antamanide complex and the Na-[Phe⁴, Val⁶]antamanide complex have been established by x-ray diffraction analyses of single crystals. The two compounds are isostructural, but not isomorphous. The complexes are folded into a globular shape with an approximate 2-fold axis. Two of the peptide linkages are in the cis conformation, Pro²-Pro³ and Pro⁷-Pro⁸. There are only two intramolecular hydrogen bonds. Four C==O groups have their O atoms directed inward to form four Li-O or Na-O ligands. The fifth ligand to the metal ion is provided by a solvent molecule. The conformation found in the crystalline state is different from any of the conformations proposed for the sodium antamanide complex in solution on the basis of nuclear magnetic resonance data.     

Primary Stability of a Hybrid Self‐Tapping Implant Compared to a Cylindrical Non‐Self‐Tapping Implant with Respect to Drilling Protocols in an Ex Vivo Model

Background: Modifications of implant design have been intending to improve primary stability. However, little is known about investigation of a hybrid self‐tapping implant on primary stability. Purposes: The aims of this study were to evaluate the primary stability of two hybrid self‐tapping implants compared to one cylindrical non‐self‐tapping implant, and to elucidate the relevance of drilling protocols on primary stability in an ex vivo model. Materials and Methods: Two types of hybrid self‐tapping implants (Straumann® Bone Level implant [BL], Straumann® Tapered Effect implant [TE]) and one type of cylindrical non‐self‐tapping implant (Straumann® Standard Plus implant [SP]) were investigated in the study. In porcine iliac cancellous bones, 10 implants each were inserted either using standard drilling or under‐dimensioned drilling protocol. The evaluation of implant‐bone interface stability was carried out by records of maximum insertion torque, the Periotest® (Siemens, Bensheim, Germany), the resonance frequency analysis (RFA), and the push‐out test. Results: In each drilling group, the maximum insertion torque values of BL and TE were significantly higher than SP (p = .014 and p = .047, respectively). In each group, the Periotest values of TE were significantly lower than SP (p = .036 and p = .033, respectively). The Periotest values of BL and TE were significantly lower in the group of under‐dimensioned drilling than standard drilling (p = .002 and p = .02, respectively). In the RFA, no statistical significances were found in implants between two groups and between implants in each group. In each group, the push‐out values of BL and TE were significantly higher than SP (p = .006 and p = .049, respectively). Conclusion: Hybrid self‐tapping implants could achieve a high primary stability which predicts them for use in low‐density bone. However, there is still a debate to clarify the influence of under‐dimensioned drilling on primary stability.     

Growth of the teaching nursing home. The Veterans Administration experience

Nursing homes are becoming increasingly involved with medical education, and the Veterans Administration (VA) has been particularly active in this movement. We conducted a system-wide survey of VA nursing home facilities to determine the degree to which they participate in medical and other professional training and the features associated with such training. Of the 116 VA nursing homes in 1987, 113 (97.4%) returned completed questionnaires. Compared to "standard" VA facilities (n = 85), "teaching" nursing homes (n = 28)--those in which physicians received at least 20 hours of training per capita annually--were significantly larger, admitted and discharged significantly more patients per occupied bed, and placed a significantly larger proportion of discharged patients in noninstitutional community settings. Care costs in the teaching nursing homes were slightly but not significantly higher, despite significant increases in levels of professional staffing and amounts of training activities in all disciplines. During the survey year, teaching nursing homes provided training experiences for 440 students, residents, and fellows in internal and rehabilitation medicine, as well as for 2,700 other health professionals. The growth of teaching nursing homes in the VA system appears to be associated with positive changes in the pattern of health-care delivery, and it is increasing the number of health-care professionals trained in long-term care.     

Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography

The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial [11C]hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, [11C]hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart.     

Quantity-guided drain management reduces seroma formation and wound infections after radical lymph node dissection: results of a comparative observational study of 374 melanoma patients

Background: Lymphatic fistulas are common complications after lymph node dissections in melanoma patients. We investigated whether drain management could improve the patient’s outcome.

Methods: Patients who underwent axillary or inguinal lymph node dissection (RALND or RILND) for malignant melanoma were recorded in a prospective database. Two different methods of drain management were compared. Either the drain was removed no later than the eighth postoperative day (period I, 2003–2007) or it was left in place until fluid flow was below 50?ml in 24?h for two consecutive days (period II, 2008–2011). The main outcome criterion was the incidence of seroma punctures after drain removal.

Results: 374 patients were analysed. The incidence of seroma punctures significantly decreased in period II. The number of patients with elevated lymphatic secretions rose by 41.3% (RALND) and 38.1% (RILND). With the exception of lymphatic fistulas, we observed significantly more local complications with need for treatment in period I (n?=?104, 52%) than in period II (n?=?31, 18%). In period II, the hospital stays after both procedures were significantly reduced.

Conclusions: We conclude that quantity-guided drain management leads to a prolonged interval of drainage but is associated with a lower incidence of seroma formation and shorter hospital stay.