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Copyright of Zoll-Profi is the property of Reguvis Fachmedien GmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zoll-Profi is the property of Reguvis Fachmedien GmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract.: Introduction: Resections of extensive tumours, recurrences and radiodermatitides at the neck cause complex defects. Free bowel transplantation enables one-stage reconstruction. Patients and Methods: In 35 out of 57 interdisciplinarily treated patients, small-bowel transplantation was performed for reconstruction. Thirty patients received cylinder grafts, five jejunal patch plastics. In four patients neoglottis formations according to Ehrenberger were performed. To cover soft tissue defects, two patients received scapular free flaps, eight patients a jejunal segment, incised at the anti-mesenteric side, the mucosa stripped and covered by a split skin graft. Results and Conclusions: Thirty-four grafts were viable. One patient received a successful re-transplantation. One postoperative fistula at the hypo-pharyngojejunostomy was closed by a seperated jejunal segment which was primarily used as monitor, two others by pectoral flaps. Separation of a jejunal graft into two or three segments enables restoration of swallowing, voice and covering soft tissue in a one-stage procedure. The whole reconstruction necessitates only one arterial and one venous microanastomosis at the neck.

Presenilin-1 (PS1) facilitates gamma-secretase cleavage of the beta-amyloid precursor protein and the intramembraneous cleavage of Notch1. Although Alzheimer's disease-associated mutations in the homologous presenilin (PS2) gene elevate amyloid beta-peptide (Abeta42) production like PS1 mutations, here we demonstrate that a gene ablation of PS2 (unlike that of PS1) in mice does not result in a severe phenotype resembling that of Notch-ablated animals. To investigate the amyloidogenic function of PS2 more directly, we mutagenized a conserved aspartate at position 366 to alanine, because the corresponding residue of PS1 is known to be required for its amyloidogenic function. Cells expressing the PS2 D366A mutation exhibit significant deficits in proteolytic processing of beta-amyloid precursor protein indicating a defect in gamma-secretase activity. The reduced gamma-secretase activity results in the almost complete inhibition of Abeta and p3 production in cells stably expressing PS2 D366A, whereas cells overexpressing the wild-type PS2 cDNA produce robust levels of Abeta and p3. Using highly sensitive in vivo assays, we demonstrate that the PS2 D366A mutation not only blocks gamma-secretase activity but also inactivates PS2 activity in Notch signaling by inhibiting the proteolytic release of the cytoplasmic Notch1 domain. These data suggest that PS2 is functionally involved in Abeta production and Notch signaling by facilitating similar proteolytic cleavages.

Mutant presenilins (PS) contribute to the pathogenesis of familial Alzheimer's disease (FAD) by enhancing the production of Abeta42 from beta-amyloid precursor protein. Presenilins are endoproteolytically processed to N-terminal and C-terminal fragments, which together form a stable 1:1 complex. We have mapped the cleavage site in the PS2 protein by direct sequencing of its C-terminal fragment isolated from mouse liver. Three different N-terminal residues were identified starting at Val-299, Thr-301, and Leu-307 that correspond closely to the previously described N termini of the C-terminal fragment of human PS1. Mutational analysis of the PS2 cleavage site indicates that the principal endoproteolytic cleavage occurs at residues Met-298/Val-299 and that the N terminus is subsequently modified by secondary proteolytic cleavages. We have generated cleavage defective PS2 constructs, which accumulate exclusively as full-length polypeptides in transfected Neuro2a cells. Functional analysis of such cleavage defective PS2 carrying the FAD mutation Asn-141 --> Ile showed that its Abeta42 producing activity was strongly reduced compared with cleavage-competent FAD PS2. In contrast, cleavage defective PS2 was active in rescuing the egg-laying defect of a sel-12 mutant in Caenorhabditis elegans. We conclude that PS2 endoproteolytic cleavage is not an absolute requirement for its activities but may rather selectively enhance or stabilize its functions.

The two homologous presenilins are key factors for the generation of amyloid beta-peptide (Abeta), since Alzheimer's disease (AD)-associated mutations enhance the production of the pathologically relevant 42-amino acid Abeta (Abeta42), and a gene knockout of presenilin-1 (PS1) significantly inhibits total Abeta production. Presenilins undergo proteolytic processing within the domain encoded by exon 9, a process that may be closely related to their biological and pathological activity. An AD-associated mutation within the PS1 gene deletes exon 9 (PS1Deltaexon9) due to a splicing error and results in the accumulation of the uncleaved full-length protein. We now demonstrate the unexpected finding that the pathological activity of PS1Deltaexon9 is independent of its lack to undergo proteolytic processing, but is rather due to a point mutation (S290C) occurring at the aberrant exon 8/10 splice junction. Mutagenizing the cysteine residue at position 290 to the original serine residue completely inhibits the pathological activity in regard to the elevated production of Abeta42. Like PS1Deltaexon9, the resulting presenilin variant (PS1Deltaexon9 C290S) accumulates as an uncleaved protein and fully replaces endogenous presenilin fragments. Moreover, PS1Deltaexon9 C290S exhibits a significantly increased biological activity in a highly sensitive in vivo assay as compared with the AD-associated mutation. Therefore not only the increased Abeta42 production but also the decreased biological function of PS1Deltaexon9 is due to a point mutation and independent of the lack of proteolytic processing.

Summary.: Patients suffering from long-untreated malignomas of the chest or abdominal wall may require plastic surgery due to extensive defects after tumor resection. Despite a variety of pedicled or free myocutaneous flaps, there are defects in which these reconstructional options may not be indicated. In these patients, the omental flaps are a valid alternative. Since a secondary split skin graft is mandatory with the omentum flap, antibacterial and granulation-enhancing xerodressings are required for wound bed conditioning. We report one patient in whom the omentum flap was used for coverage of an extensive defect after resection of a widespread basal cell carcinoma at the lateral thorax and abdominal wall. After wound conditioning with silver-impregnated activated charcoal xerodressing (Actisorb) in combination with a hydroactive polymer dressing (Allevyn), secondary skin grafting was performed. In this patient fibrosis and calcification of the omentum led to stable abdominal wall coverage even without the application of a synthetic mesh.

Secondary postoperative ischaemia due to venous occlusion is the most detrimental insult to free microvascular flaps. In an experimental rat free flap model the efficacy of long acting prostacyclin analogues iloprost (Ilomedin™) and cicaprost in venous occlusion induced postoperative ischaemia was studied. Free, microvascular groin flaps were transplanted to the neck and the draining veins were temporarily occluded on the first postoperative day for a total of 20 min. In the untreated control group, haemorrhagic flap necrosis occurred. Intravital microscopy after secondary ischaemia revealed flap areas without reperfusion. The functional vessel density was significantly reduced. Reperfused capillaries were tortuous and significantly dilated. After reperfusion the interstitial leakage of macromolecular dextran increased, indicating loss of microvascular endothelial integrity. Intra-arterial and intravenous applications of iloprost were able to diminish the ischaemic effects, giving a flap survival rate of 83%. Similar results were obtained by intravenous and enteral administration of cicaprost. Transcutaneous oxygen partial pressure measurements confirmed the viability of the surviving flaps. We conclude that both iloprost and cicaprost are effective in preventing venous occlusion induced failure of free microvascular groin flaps. Copyright 1999 The British Association of Plastic Surgeons

The tet operators of two naturally evolved tetracycline resistance determinants differ by a G.C to A.T transition at the sixth base pair. This mutation prevents heterologous recognition of these tet operators by their respective two Tet repressor proteins. The amino acid side chains responsible for this sequence‐specific distinction of operators were determined. For this purpose in vitro recombinants of the two tetR genes were constructed. Restriction sites were introduced by oligonucleotide‐directed mutagenesis in both genes followed by the exchange of different coding segments between them. The encoded chimeric Tet repressor proteins were expressed and their operator recognition specificity was scored in vivo. Exchanging gradually smaller coding segments led finally to a single amino acid exchange in both genes at position 40 of the primary structures. Each Tet repressor containing Thr at this position recognizes the G.C operator while those with Ala recognize the A.T operator regardless of the rest of the sequences. This result demonstrates clearly that the amino acid 40 of Tet repressor contacts and recognizes base pair 6 of tet operator. Sterical interference of the large Thr side chain with the methyl group of A.T and a possible involvement of the hydroxyl in hydrogen bonding to the operator are discussed as the molecular basis of this differentiation between A.T and G.C base pairs.

Each of 22 amino acids in the proposed alpha‐helix‐turn‐alpha‐helix operator binding motif of the Tn10 encoded Tet repressor was replaced by alanine and one residue was replaced by valine to determine their role in tet operator recognition by a ‘loss of contact’ analysis with 16 operator variants. One class of amino acids consisting of T27 and R28 in the first alpha‐helix and L41, Y42, W43 and H44 in the recognition alpha‐helix are quantitatively most important for wild‐type operator binding. These residues are probably involved in the structural architecture of the motif. A second class of residues is quantitatively less important for binding, but determines specificity by forming base pair specific contacts to three positions in tet operator. This property is most clearly demonstrated for Q38 and P39 and to a lesser extent for T40 at the N‐terminus of the recognition alpha‐helix. The contacted operator base pairs indicate that the N‐terminus of the recognition alpha‐helix is located towards the palindromic center in the repressor‐operator complex. Although the orientation of the recognition alpha‐helix in the Tet repressor‐tet operator complex is inversed as compared with the lambda‐ and 434 repressor‐operator complexes, the reduced operator binding of the TA27 mutation in the first alpha‐helix suggests that the hydrogen bonding networks connecting the two alpha‐helices may be similar in these proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphedemas due to a local blockade of the lymphatic system can be treated by bridging the defect with autolo-gous lymphatic grafts. Under the microscope, grafts are anastomosed to peripheral lymphatics distal to and central lymphatics proximal to the regional blockade. In this way, the diminished transport capacity can be restored.

Summary 162 patients had a McKissock's reduction mammaplasty between 12.78 and 4.85. The areola is transposed thereby on a cranio-caudal flap. A questionaire and a checkup was performed 3 1/2 years postop., 57 % found the results very good and good, 31% satisfactory, 3 % adequate, 6 % imperfect and 3 % bad. The sensibility of the nipple was almost unchanged in 40 %. Erectibility of the nipple was in most cases present. The measures of the breast changed only little after 3 1/2 years.

We performed a mutational analysis of the left half of Tn10-encoded tet operator O2, located in the 5' nontranslated region of the mRNA for the resistance protein TetA, and determined the importance of that region for translation efficiency and mRNA stability. Transcriptional fusions of 17 mutants to lacZ expressed the same amounts of beta-galactosidase, while translational fusions varied 35-fold in expression efficiency. The mRNA half-lives varied 24-fold, with 9.6 min for the most highly expressed mRNA and 0.4 min for the least efficiently expressed mRNA. Toeprint experiments were performed to distinguish whether these mutations define a determinant of mRNA stability or influence translation initiation. The highly expressed mRNA was 24-fold more efficient in forming the initiation complex in vitro than the low-expression mutant. It was concluded that this sequence, albeit located upstream of the ribosome-binding sequence, is an important determinant for efficient initiation of translation. Secondary-structure calculations of the mRNAs revealed no correlation of the potential to form double strands masking the ribosome-binding sequence with expression efficiency.

Rats were subjected to burns extending to 15% of their body surface. Enzyme activities were measured by a slightly modified Barrett technique between the 12th and 18th day after the burn injury. A statistically significant activation of acid proteolytic enzymes, in relation to mg protein, was seen in liver, spleen, kidney and stomach. In relation to grams fresh weight, an activation was seen in the kidney. Necrotic skin subsequent to burn injury showed a marked rise in activation compared with the skin of the control group, as well as with the skin of the burned animals. Increased enzyme contents were also detected in the intact skin of burned animals, compared with the skin of the control group.

The majority of cases with familial Alzheimer's disease (FAD) are linked to mutations of the presenilin (PS) genes. These genes show considerable sequence similarity to the sel-12 gene of Caenorhabditis elegans, which has been postulated to function in the facilitated signalling by lin-12 and glp-1. In order to analyse the functional conservation of the presenilins, we introduced the human PS-1 cDNA, as well as clinical and deletion mutant proteins, into sel-12 mutant animals and tested their potential to rescue the egg-laying defect. Human PS-1 expressed from the sel-12 promoter fully rescued the sel-12 phenotype, whereas two missense mutations, C410Y and A246E, identified in pedigrees with FAD, exhibited a strongly decreased rescuing activity. The large hydrophilic loop and transmembrane domain 7 are required for the biological activity of PS-1. PS-1 protein was proteolytically cleaved in C. elegans as it is in human cells. A PS-1 splice variant (FAD mutation Deltaexon9) that does not undergo proteolytic cleavage also substituted for sel-12. The conservation of function of human PS-1 and C. elegans sel-12 suggests that presenilin proteins are required, directly or indirectly, for the proper operation of the Notch signalling pathway. FAD-associated mutant proteins tested showed different rescuing activities, indicating that they might affect different functional or regulatory aspects of PS-1. Proteolytic processing is not a prerequisite for PS-1 function in C. elegans.

Refinements in microsurgery have made it possible to perform causal therapy on lymphedemas due to a local blockade of lymphatic pathways through transplantation of the patient's lymph collectors. End-to-end anastomoses with lymphatics before and after the blockade or crossing to the opposite side are performed under 40-fold magnification. Between July 1980 and February 1985 32 patients received this treatment. 23 patients had postmastectomy edema, and 9 patients had unilateral edema of the lower limb (2 primary, 7 secondary edemas). The lasting result was that the volume difference between the affected and the healthy limb decreased to about 65%. Lymphatic scintiscans showed improved lymphatic transport capacity with increasing time from surgery and long patency of the grafts.

In the last 10 years an increasing number of cases of group A streptococcal toxic shock syndrome have appeared in various clinical settings. The manifestation of this syndrome includes rapidly progressive multiorgan failure and soft-tissue necrosis.

Zusammenfassung: Es wird ein Fall von akuter Bleiintoxikation, hervorgerufen durch Aufnahme von 6 g Bleigltte, mitgeteilt. Nach baldigem Abklingen der akuten Erscheinungen kommt das Krankheitsbild einer chronischen Bleiintoxikation mit ausgesprochener Anmie zur Beobachtung. Die Krankheitserscheinungen verschwanden nur sehr langsam. Bemerkenswert ist vor allem die anfangs bestehende Stomatitis, die nur bei auf oralem Wege entstandener akuter (nicht gewerblicher) Bleivergiftung zuweilen beobachtet worden ist, und das Auftreten von Schmerzen im Bein mit Gehstrungen (ohne Befund). Die Untersuchung von Stuhl und Urin auf Bleigehalt hatte stets ein negatives Ergebnis. Baarder hat besonders darauf aufmerksam gemacht, da bei frischen Vergiftungen kein Blei in den Ausscheidungen gefunden wird, weil es der Krper zunchst zurckhlt und erst allmhlich wieder ausscheidet. Andere Schwermetalle zeigen ein hnliches Verhalten. Der diagnostische Wert der Urin- und Stuhluntersuchungen auf Blei ist daher gering.

Zusammenfassung Kurze Schilderung eines äußerst ungewöhnlich lokalisierten und begrenzten Spontan-Ventilpneumothorax mit differentialdiagnostischer. Abgrenzung desselben.

Der Einfluß von Tabakrauch und Nicotin auf den Rhodanidstoffwechsel.

Summary A free flap can be harvested leaving an inconspicuous donor site in the lower gluteal region. The different possibilities of free transplantation depend above all on the microvascular supply within the flap. We have prepared gluteal flaps in ten autopsies. The inferior gluteal artery was perfused with a solution of lead oxide and gelatin. After fixation in formaldehyde, the flaps were dissected in three layers and radiographs were taken. Larger branches of the inferior gluteal artery were found even in the superficial subcutaneous tissue. They give rise to smaller vessels which form a muscular, an epifascial and a subdermal subcutaneous network. The inferior gluteal flap is, thus, supplied in all three compartments by the inferior gluteal artery. The isolation of a free subcutaneous compartment as a free tissue transfer seems to be possible, and flap thinning is favored in the middle subcutaneous tissue.

Summary The type of surgery is determined by the histopathology. Proliferative mastopathia: controls. Atypically proliferative mastopathia and ductular papilloma: short-term controls, usually subcutaneous mastectomy. Solitary ductular papilloma: ductectomy. Lobular carcinoma in situ: subcutaneous mastectomy. Noninvasive intraductular carcinoma: modified radical mastectomy with nipple in waiting position. Invasive carcinoma: (T1–2N0–1) modified radical mastectomy except medial localization. Reconstruction is allowed with: noninvasive carcinoma: immediately. T1N0M0 after 6 weeks. T2N0M0 after 3 years. T1–2N1M0 after 5 years free of recurrence. Our own techniques of reconstruction, i.e. subcutaneous mastectomy, rotation flap, and advancement flap are demonstrated in detail.

Summary The surgical treatment of chronic lymphedema of the upper limb by transposition of superficial lymphatics into the deep compartment of the limb by a modification of Thompson's method is given in detail, and the long-term results after 1–7 years of follow-up in 55 patients is considered. The results obtained were classified with reference to the criteria of Thompson and Kinmonth as good in 35 cases (63.6%), satisfactory in 18 (32.7%), and poor in 2 (3.6%) patients.

Summary Autologous transplantation of lymphatic vessels with lympholymphatic anastomoses peripheral and central to the blockage is a causal therapy for lymphostatic edemas. From June 1980 to February 1982 lymphatic vessel transplantation using donated lymphatic channels of the medial superficial system of the thigh was performed in ten patients suffering from edemas of the upper and lower extremities. The maximum difference in circumference as well as the excessive volume was reduced by about 60%. This effect was maintained during a mean observation period of 6.5 months. The improvement of lymph transporting capacity could be demonstrated in eight patients by lymphatic scintiscan.

Malignant cutaneous melanomas are prognostically variable, histogenetically and diagnostically heterogeneous malignant tumors that stem from pigment-producing cells. Therefore, the therapeutic approach depends on exact differentiation at diagnosis, as to (1) clinical stages: I = primary lesion; II = metastases limited to the regional lymph nodes; III = distant metastases, (2) clinical and histological characteristics, which are different for lentigo malignant melanoma (LM), superficial spreading melanoma (SSM), and primary nodular melanoma (NM), (3) histologic depth of tumor-cell invasion: intradermal with intact basement membrane (level I); through basement membrane down to the papillary dermis (level II); papillary dermis down to the reticular dermis (level III); throughout the reticular dermis (level IV); subcutaneous fat (level V). Therapeutic measures: if the diagnosis is doubtful excision biopsy should be performed under a general anesthetic with a margin of 2 cm (1 cm on the face), and immediate diagnosis should be made from frozen sections. Otherwise all tumor material should be removed down to the fascia, with a margin of 5 cm, and this should be followed immediately by plastic surgery to cover the defect with material from contralateral areas. In clinical stage III, immunochemotherapy with DTIC and BCG is indicated, or if only cutaneous metastases are present, external immunotherapy with DNCB or BCG. Maligne Melanome der Haut sind prognostisch unterschiedlich zu beurteilende, histogenetisch und diagnostisch heterogene bösartige Tumoren, die ihren Ausgang von pigmentbildenden Zellen nehmen. Deshalb richtet sich auch das therapeutische Vorgehen nach einer sorgfältig differenzierenden Diagnostik. (1) Klinische Stadien: I = Primärtumor (PT);II = PT mit regionalem Lymphknotenbefall; III = Fernmetastasen. (2) Klinische und histologische Abtrennung von Lentigo-maligna-Melanom (LM), superfiziell spreitendem Melanom (SSM) und primär knotigem Melanom (NM). (3) Histologische Angabe der Invasionstiefe: Intraepidermal, oberhalb der Basalmembran (Niveau I); Durchbruch der Basalmembran ins Str. papillare (Niveau II); Str. papillare bis zur Grenzzone zum Str. reticulare (Niveau III); gesamtes Str. reticulare (Niveau IV); Subkutis (Niveau V). Therapeutisches Vorgehen: Bei diagnostischen Zweifeln Excisionsbiopsie in Vollnarkose mit einem Sicherheitsabstand von 2 cm, Schnellschnittdiagnose. Ansonsten Entfernung des Tumors mit einem 5 cm-Sicherheitsabstand, gemessen von der Tumorperipherie und tiefenwärts bis zur Muskelfascie, anschließend sofortige Deckung mit einem Transplantat von kontralateralen Körperpartien. Im Gesicht, an Händen und Füßen modifiziertes Vorgehen. Bei klinischem Stadium III zusätzlich Immunochemotherapie mit DTIC und BCG, bei rein cutanen Metastasen auch alleinige äußerliche Immunotherapie mit DNCB oder BCG.

Summary Burn scar contractures of the cervical region may be corrected by full-thickness and thick split-thickness skin grafts. The splinting pressure technique makes possible the use of split-thickness skin grafts as the treatment of choice, just as in most other locations. Alternative techniques include transposition flaps and microvascular flaps. In limited contractures in the extremities Z-plasties may be successfully used. If nerves or vessels are exposed, correction by flaps is necessary.

Summary To prepare for clinical allogeneic lymph vessel transplantation, 21 abdominal thoracic duct segments were transplanted from BDIX to LE rats. Electron microscopy showed a transitory loss of endothelium followed by complete recovery of the endothelial layers by 15 days after transplantation. The vessel wall remained stable despite considerable changes in the structure of collagen. Nevertheless, the function of the transplants was not substantially altered by these changes, as shown by staining techniques.

Summary The modified radical mastectomy with the obliquus incision is much more convenient for the reconstruction than the radical mastectomy at the same survival rate. The prognosis based on the first pathological findings determines the reconstruction. Tumors (T1) less than 2 cm in diameter rarely develop axillary metastases and local recurrencies. Therefore the breast can be reconstructed after 6 weeks. Dealing with larger tumors (T2) the possible development of 80% of local recurrencies has to be waited for within 3 years. In the case of axillary metastases the reconstruction may be performed after 5 years provided that no recurrence has been detected.

Summary Lymphostatic edema of an extremity is caused by a functional disorder of the lymph evacuation capacity. This capacity can be measured in a reproduciable way with high specific and sensitivity by quantifying the lymphatic scintiscan. The evacuation index can be determined by lymphatic transport kinetics, the distribution pattern of the radiopharmaceutical, the time to appearance in the lymph nodes, assessment of lymph nodes, and assessment of lymph vessels. In 23 patients with lymph edema the transport index was significantly improved after autologous lymph vessel transplantation.

Summary Lymphedemas caused by a regional blockade of the lymphatic outflow can be compensated by direct reconstruction of the interrupted lymphatic system. Lymph vessels with a length of up to 30 cm are taken from the inner part of the thigh. In postmastectomy edema, they are interposed between ascending lymph vessels at the upper arm and the deep lymph collectors at the neck. In unilateral edema of the leg, the transplants are transposed via the symphysis. End-to-end anastomoses are made using the so-called tension-free anastomosing technique. The patency of the transplants is shown clinically by reduction of the affected extremity and can be demonstrated by lympho-scintigraphy.

Summary Exact fitting of the skin to the prosthesis is important for the avoidance of fibrosis after subcutaneous mastectomy. A suitable method, developed by the authors, for skin reduction and nipple transposition is illustrated with diagrams and photographs. A method used by the authors for recontruction of the breast after radical mastectomy consists in reconstruction of the missing skin by means of a triangular rotation flap from the abdominal and thoracic wall and with the base in the median line, insertion of a silastic implant in a second stage, and reconstruction of the nipple and areola by means of a full-thickness skin graft taken from the labia minora. Details are illustrated with diagrams.

Summary Defect wounds over 92 joints on 54 patients were resurfaced with mesh skin grafts. Thirsch grafts often produce dermatogenic contractures due to shrinkage of the graft, but this does not occur with mesh grafts as the elastic parts of the split graft are cut with a mesh dermatome. The advantage of good wound drainage results in an excellent quota of graft takes, even on poor recipient areas or infected or fresh wounds. In none of the cases properly operated on was dermatogenic contracture seen. In functional, esthetic and mechanical respects results were always good.