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M Sachs

Publications and source records attributed to M Sachs.

At least 37 records · Page 2Linked to original sources

[History of surgical instruments. 9. Surgical instruments and development of surgical technique of lithotomy incision].

Lithotomy, i.e. the surgical method of cutting for stone in the bladder, belongs to the oldest and, due to the high risk, most notorious operating techniques. Records of stone-cuttings date as far back as Ancient Greece. The first detailed description of the procedure and instrumentation of lithotomy is to be found by Celsus (1. century AD). The patient in the lithotomy position, the neck of the bladder is approached by a median incision of the perineum. Celsus is also the first to mention special stone-hooking instruments ("uncus") to aid in extracting the bladder-stones. Medico-historical development lead to constant changes in the technique as well as in the instrumentation, since the lack of analgesia and anaesthesia necessitated quick operations of only a few minutes. A key step in the progress of operation was the introduction of so-called path-finders and directing probes in the 16th century. The opening of the bladder from the perineal incision was now accompanied by the simultaneous admission of a metal catheter into the bladder via urethra, thus providing the "Lithotomist", through manual control of the catheter, with an enhanced orientation towards the position of urethra and bladder. At that time, the dissection was conducted bluntly and without direct view of the situation, i.e. without an exact representation of the structures to be separated. Thanks to the improved instrumentation, the instruments could now be guided along a probe directly into the bladder, thus alleviating the tedious search for the opening after changing instruments, all the while with an agitated, pressing patient. Famous names in the development of the lithotomy with an perineal incision are the medical doctor Mariano Santo (around 1488-1564), the barber-surgeon Frère Jacques de Beaulieu (1651-1719) and later Johann Jakob Rau M.D. (1668-1719). Only later, to avoid injury to the perineum, the suprasymphyseal approach ("Sectio alta") was adopted (primarily by Pierre Franco 1556). Due to the construction of arrow-like probe by the barber-surgeon Frère Come (Jean Baseilhac [1703-1781]), which was pushed through the urethra into the bladder and up and above the symphysis, the danger of damaging or penetrating the peritoneum was greatly reduced. In the 19th century the upper lithotomy prevailed as the standard operating method over the perineal approach, known even by the ancient Greeks, but marked by its high complication rate. Since the end of the 19th century, however, the upper lithotomy in ist turn, has been nearly completely replaced by the cystoscopic transurethral lithotripsy.

Cystostomy↗

[Not Available].

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Germany↗

Reconstitution of mammary gland development in vitro: requirement of c-met and c-erbB2 signaling for branching and alveolar morphogenesis.

We have established a cell culture system that reproduces morphogenic processes in the developing mammary gland. EpH4 mouse mammary epithelial cells cultured in matrigel form branched tubules in the presence of hepatocyte growth factor/scatter factor (HGF/SF), the ligand of the c-met tyrosine kinase receptor. In contrast, alveolar structures are formed in the presence of neuregulin, a ligand of c-erbB tyrosine kinase receptors. These distinct morphogenic responses can also be observed with selected human mammary carcinoma tissue in explant culture. HGF/SF-induced branching was abrogated by the PI3 kinase inhibitors wortmannin and LY294002. In contrast, neuregulin- induced alveolar morphogenesis was inhibited by the MAPK kinase inhibitor PD98059. The c-met-mediated response could also be evoked by transfection of a c-met specific substrate, Gab1, which can activate the PI3 kinase pathway. An activated hybrid receptor that contained the intracellular domain of c-erbB2 receptor suffices to induce alveolar morphogenesis, and was observed in the presence of tyrosine residues Y1028, Y1144, Y1201, and Y1226/27 in the substrate-binding domain of c-erbB2. Our data demonstrate that c-met and c-erbB2 signaling elicit distinct morphogenic programs in mammary epithelial cells: formation of branched tubules relies on a pathway involving PI3 kinase, whereas alveolar morphogenesis requires MAPK kinase.

Androstadienes↗

Engineered mutants of HGF/SF with reduced binding to heparan sulphate proteoglycans, decreased clearance and enhanced activity in vivo.

BACKGROUND: Although a number of growth factors bind cell-surface heparan sulphate proteoglycans (HSPGs), the role of this interaction is unclear except for fibroblast growth factor which requires HSPG binding for signalling. Hepatocyte growth factor/scatter factor (HGF/SF) plays important roles in mammalian development and tissue regeneration and acts on target cells through a specific receptor tyrosine kinase encoded by the c-met proto-oncogene. This factor also binds HSPGs with high affinity, but conflicting data have been reported on the role of HSPG binding in HGF/SF signalling. RESULTS: To map the binding sites for HSPG and the Met receptor in HGF/SF, we have engineered a number of HGF/SF mutants in which several clusters of solvent-accessible residues in the hairpin structure of the amino-terminal domain or in kringle 2 have been replaced. Two of the mutants (HP1 and HP2) showed greatly decreased (more than 50-fold) affinity for heparin and HSPGs but retained full mitogenic and motogenic activities on target cells in culture. Furthermore, when compared with wild-type HGF/SF, the HP1 mutant exhibited a delayed clearance from the blood, higher tissue levels and a higher induction of DNA synthesis in normal, adult murine liver. CONCLUSIONS: These results establish the following: the binding sites in HGF/SF for Met and for HSPGs can be dissociated by protein engineering; high-affinity binding of HGF/SF to HSPGs is not essential for signalling; one role of HSPG binding in the HGF/SF system appears to be sequestration and degradation of the growth factor; and HGF/SF mutants with decreased affinity for HSPGs exhibit enhanced activity in vivo.

Animals↗

[Inflammatory esophageal stenosis with intramural pseudodiverticulosis of the esophagus].

Esophageal intramural pseudodiverticulosis is a very rare disease with unknown etiology, which especially affects male patients between 45 and 65 years. This disease is characterized by dilatation of the esophageal submucosal glands and their outlets. Stenosis caused by esophagitis due to intramural pseudodiverticulosis is found in most of the known patients. All patients presented with dysphagia, usually of long duration. The characteristic radiographic appearance is numerous intramural esophageal contrast-filled diverticulosis-like pouches--4 mm in depth.

Diagnosis, Differential↗

Historical development of surgical instruments exemplified by hemostatic forceps.

We describe the historical development of surgical instruments exemplified by hemostatic forceps, starting with antique and medieval forceps used for the arrest of bleeding to modern atraumatic hemostatic forceps used for vascular reconstruction. Their development proceeded mainly in three steps: (1) development of ligature forceps directly for hemostasis (Celsus, first century AD; Paré, 1582; L. Heister, 1743; (2) development of atraumatic forceps, which facilitate vascular reconstruction or anastomosis creation by temporarily clamping vessels (Höpfner, 1903; Stich, 1907; Jeger, 1913; (3) construction of tangential forceps, which, by partially clamping vessels with partial maintenance of blood flow, allow the reconstruction or anastomosis of large vessels in a side-to-side technique. The first tangential occlusion clamp was developed by Friedrich Trendelenburg (1844-1924) in 1908, when he established the operative treatment for embolism of the pulmonary artery. This clamp was later modified by A. W. Meyer (1927) and V.P. Satinsky (ca. 1950).

Hemostasis, Surgical↗

[Not Available].

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Disease↗

[The so-called Spigelian hernia--a rare lateral hernia of the abdominal wall].

A patient with Spigelian hernia is presented and the main pathological and clinical features are discussed. Its true incidence is probably greater than the small number of patients reported in the literature due to failure to recognize the clinical picture. A hernia through a defect in the Spigelian fascia (aponeurosis of the transverse muscle of the abdomen) is called Spigelian hernia. The semilunar (Spigelian) line is defined as the line forming the transition from muscle to aponeurosis in the transverse muscle of the abdominal wall. It is a lateral convey line between the costal arch and the pubic tubercle. The part of the aponeurosis that lies between this semilunar line and the lateral edge of the rectus muscle is called the "Spigelian fascia" (correct: Spigelian aponeurosis). The hernia is located intramurally because the hernia is covered by the aponeurosis of the external oblique aponeurosis, so that both, the hernial sac and the orifice, can often not be detected by palpation. Clinical symptoms are not characteristic but most patients have a distinct tender point above the hernial orifice.

Abdominal Muscles↗

[History of surgical instruments: 7. The first electrosurgical instruments: galvanic cauterization and electric cutting snare].

In 1854 the surgeon Albrecht Theodor Middeldorpf (1824-1868) published the first monography on the application of electrical current in surgical operations ("galvanocautery"). By galvanocautery Middeldorpf defined a procedure in which specially constructed parts of surgical instruments (usually thin platinum wires) were transformed into glowing heat by means of galvanic current from a zinc-platinum-battery. In this manner it was possible to perform dissection and destruction of tissue as well as coagulation of vessels for hemostasis. His most important electrosurgical instruments comprised an electrosurgical knife ("galvanocautery") and the electrical cutting snare ("ligatura candens") for removal of polypoid tumors. These instruments are the direct ancestors of modern electrocautery or cautery snare. The glowing platinum wire was later also applied as a light source of cystoscopes. Thus, galvanocautery enabled development of endoscopy. Modern diathermy with high-frequent alternating current was introduced in medicine by the Dermatologist Franz Nagelschmidt from Berlin.

Electrocoagulation↗

[History of surgical instruments: 8. Instruments and development of amputation technique exemplified by amputation sets from the middle of the 19th century].

The amputation of a limb is one of the oldest surgical procedures. However, in the course of medical history operative techniques and surgical instruments have been improved continuously. With an example of an amputation case of the last century we will summarize this development until the middle of the nineteenth century. Even in the first century Celsus gave a description of an amputation (circular cut). A major step in the development of the operative technique was the introduction of artery forceps by A. Paré in the sixteenth century. Nevertheless, due to a lack of analgesics and narcotics the operation had to take only a few minutes. Therefore the amputation was completed in one cut, i.e. detachment of the skin, muscles and bone at the same level. This technique known as "classic circular cut" was modified several times in the following period: in order to reduce suture tension Petit recommended to transect the skin first and the muscles and bone more proximal ("two-stage circular cut", 1718) and Bromfield approved to cut in turn the skin first, the muscles more proximal and the bone most proximal ("three-stage circular cut", 1773). Finally, Lowdham (1679), Verduyn (1696) and C. J. M. Langenbeck (1810) changed the operative technique to the effect that they used a soft-tissue flap in order to cover the bone without tension ("flap amputation").

Amputation, Surgical↗

[The common surgical heritage].

The mutual and dreadful history of Poland and Germany has left behind wounds and scars on both sides. This session is dedicated to the common surgical heritage and joint development of the presence and future. Important pioneering contributions of German surgery were achieved at the University of Breslau (Wroclaw), especially by Johann von Mikulicz-Radecki and his associate Ferdinand Sauerbruch. Our Polish colleagues have further developed the surgical tradition in Poland since World War II.

General Surgery↗

Hepatocyte growth factor/scatter factor (HGF/SF) signals via the STAT3/APRF transcription factor in human hepatoma cells and hepatocytes.

Acute phase protein expression is regulated by a variety of cytokines such as IL-1, IL-6, IL-11, tumour necrosis factor alpha, interferon-gamma, oncostatin-M, leukemia inhibitory factor, ciliary neurotrophic factor and cardiotrophin-1. Presently, IL-6 is regarded as the most potent mediator of acute phase protein (APP) synthesis. It was shown that IL-6 and IL-6-type cytokines activate the so-called JAK/STAT pathway and finally regulate APP expression in liver cells. Since HGF/SF is also capable of regulating APP expression, we asked whether it might also signal via the JAK/STAT pathway. Here we show that incubation of human hepatocytes as well as hepatoma cells (HepG2) with HGF/SF results in activation of the transcription factor STAT3. This STAT3 activation after HGF/SF did not occur before 5-7 h and was maintained up to 28 h. These observations are in contrast to the rapid and transient activation of STAT1 and STAT3 mediated by IL-6.

Carcinoma, Hepatocellular↗

Role of HGF/SF and c-Met in morphogenesis and metastasis of epithelial cells.

We have analysed the role of hepatocyte growth factor/scatter factor (HGF/SF) in the process of morphogenesis and metastasis of epithelial (carcinoma) cells. HGF/SF induces various morphogenic responses in epithelial cells that derive from different tissues when these are grown in three-dimensional gels, e.g. branching tubules in kidney, breast, and prostate epithelial cells, crypt-like structures with brush border in colon epithelial cells, and alveolar-like aggregates in lung and pancreas cells. Epithelial cells are thus able to form complex structures in vitro which resemble the structures formed in the organ they originate from. We also examined the response of human breast carcinoma cells to HGF/SF in vivo. MDA MB 435 cells transfected with HGF/SF were injected into the mammary fat pad of nude mice, where they form tumours which spontaneously metastasize to the lungs. We found that expression of HGF/SF promoted metastasis whereas expression of the cell adhesion molecule E-cadherin was inhibitory. Moreover, expression of E-cadherin reconstituted the ability of the cells to form complex structures in response to HGF/SF in vitro. These data demonstrate that the different responses to HGF/SF depend on the state of the epithelial cells: morphogenesis requires epithelial differentiation and cell polarity, whereas metastasis is observed when the cells have lost their epithelial characteristics. Moreover, we have recently identified Gab-1 as a direct-binding substrate of the c-Met receptor. Gab-1 binds to c-Met phosphorylated on tyrosine residues, but not to a number of other tyrosine kinases from different subfamilies. A newly identified proline-rich domain of Gab-1 is responsible for the binding to the bidentate docking site in c-Met. Expression of Gab-1 in epithelial cells is sufficient to induce c-Met-specific cellular responses which include the formation of branching tubules. Thus, Gab-1 seem to correspond to the substrate of the c-Met receptor tyrosine kinase that mediates the epithelial morphogenesis.

Animals↗

Historical evolution of inguinal hernia repair.

When analyzing original articles since the sixteenth century, it becomes apparent that all surgical techniques for repair of the inguinal hernial orifice can be traced back to two simple repair principles. The first is reinforcement of the anterior wall of the inguinal canal and tightening of the external inguinal ring (Stromayr 1559, Purmann 1694, Czerny 1877), and the second is reinforcement of the posterior wall of the inguinal canal and the tightening of the internal inguinal ring, either externally (Lucas-Championnière 1881, Bassini 1889, Lotheissen 1898, McVay 1942, Shouldice 1945, Lichtenstein 1987, Stoppa 1989) or via an intraabdominal approach by laparotomy (Tait 1891) or laparoscopically (Ger 1990, Velez and Klein 1990). We have tried to provide a systematic order to the diverse procedures of surgery of inguinal hernias according to their repair principles. We also point out their historical development.

General Surgery↗

[Early detection of TUR(transurethral resection) syndrome--ethanol measurement in ventilated patients].

A major complication of transurethral resection of the prostate (TURP) is the excessive absorption of irrigation solution resulting in hypervolemia and dilutional hyponatremia. Marking the irrigation fluid with ethanol is a method for the early detection of fluid absorption. Currently this method is being used in spontaneously breathing patients undergoing regional anaesthesia. The goal of this study was to determine whether this method is also reliable for patients undergoing general anaesthesia. Fifty-nine patients underwent TURP in either spinal anaesthesia (SPA), or general anaesthesia with semi-open (ITNO) and semi-closed (ITNC) systems. Plasma alcohol concentrations ([Eth]p), exhaled ethanol ([Eth]e), plasma sodium concentration ([Na+]), and central venous pressure (CVP) were measured. The irrigation fluid contained ethanol in an concentration of approx. 1%. We assumed that significant fluid absorption took place when [Eth]p exceeded 0.1/1000. Measurements were performed immediately prior to and during surgery at 10-minute intervals. [Eth]p correlated directly with [Eth]e for both forms of anaesthesia. [Eth]p and [Na+] correlated inversely both for SPA and ITNC. Changes in [Eth]p did not parallel changes in CVP. Clinically relevant episodes of fluid absorption were accompanied by the detection of exhaled ethanol in all groups. We conclude that measuring exhaled ethanol is a minimal invasive monitoring technique that allows the detection of significant fluid absorption in both spontaneously breathing as well as ventilated patients with sufficient sensitivity. The ethanol levels are not predictive of the sodium concentration both in SPA and general anaesthesia. Thus, additional determinations of [Na+] is recommended whenever [Eth]e exceeds 0.2/1000.

Anesthesia, General↗