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Biomedical subjects

G Mark

Publications and source records attributed to G Mark.

At least 19 recordsLinked to original sources

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

The release of toxic oxidative free radicals induced by ischemia and reperfusion may jeopardize liver graft function. N-acetylcysteine (NAC) has shown protective effects on hypothermic and warm ischemia reperfusion liver injury in animals. NAC improves hemodynamics and survival rates in patients with fulminant hepatic failure. The aim of this study was to investigate whether intraoperative treatment with NAC would improve hemodynamics and postoperative graft function in liver transplantation. Sixty patients with chronic end-stage liver disease were included in a prospective randomized placebo-controlled study. NAC or the same volume of 5% glucose was started during the anhepatic phase. Hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure. Postoperative graft function was assessed by measurements of aminotransferases, prothrombin time, and monoethylglycinexylidide test over the 3 first postoperative days. Patient demographics were similar before the infusion of NAC or glucose. Hemodynamic parameters, oxygen consumption, oxygen delivery, oxygen extraction ratio, and lactates were not different throughout the procedure. One hour after the revascularization of the hepatic artery, the oxygen extraction ratio by the liver was similar (17% +/- 7.6% v 17% +/- 6.2%) in both groups. Postoperative graft function was comparable within the 3 first postoperative days. This study failed to show any beneficial effect of the intraoperative administration of NAC on hemodynamics and graft function in liver transplantation in patients with chronic liver disease.

Acetylcysteine

Characterization of recombinant hepatitis B surface antigen using surface plasmon resonance.

Two commercial monoclonal antibodies were shown to interact with distinct epitopes within the major antigenic a determinant region of yeast recombinant hepatitis B surface antigen (rHBsAg) particles, contained in the hepatitis B vaccine, by using the surface plasmon resonance phenomenon on a BIAcore system. Apparent avidity for these antibodies were compared among different rHBsAg batches, showing the consistency of these epitopes. Furthermore, the effect of the alteration of these epitopes, achieved by chemical modifications, was readily reflected by changes in the apparent avidity for these antibodies. The procedures used in the present study provide a novel and efficient way to characterize rHBsAg particles present in different hepatitis B vaccine products.

Antibodies, Monoclonal

[Granulomatous tumor of the flexor tendon sheath as first manifestation of sarcoidosis].

While osseous tumors of the phalanges are more common, soft-tissue manifestations in the hand are uncommon in patients with sarcoidosis. Our patient presented with a large but painless tumor on the palmar aspect of the right index finger limiting finger flexion. Histology of a biopsy specimen was interpreted as a granuloma of sarcoidosis. Further X-ray investigations revealed large bilateral formations in the hila of the lung interpreted as stage I sarcoidosis in an otherwise healthy individual. Tuberculosis and polyarthritis were excluded by standard tests. The tumor was then radically excised, as it was located within the flexor tendon sheath. After uneventful wound healing the patient had regained full function of his finger at six weeks follow up. Interestingly enough, a chest film at that time showed the hilar changes to have decreased as well, which is considered quite typical for this disease.

Adult

Affinity maturation of a high-affinity human monoclonal antibody against the third hypervariable loop of human immunodeficiency virus: use of phage display to improve affinity and broaden strain reactivity.

The present study set out to investigate whether phage display could be used to improve the properties of a high-affinity human monoclonal antibody directed against the third hypervariable loop (V3 loop) of human immunodeficiency virus (HIV). The aim was to increase affinity through slowing the dissociation rate (off-rate constant of koff), whilst retaining the ability of this antibody to bind diverse V3 loop sequences. When reformatted as a scFv, the antibody fragment retained the properties of the parental IgG, including the ability to neutralise virus. Heavy and light chains were sequentially replaced with repertoires of variable domains from non-immunised human donors followed by selection on biotinylated synthetic peptide. All selected variants derived from the same germline as the parental antibody. Variants of the light chain provided little if any improvement, whereas two residue changes in VHCDR2 and one in VHFR3 resulted in a reduced koff from gp120 protein of the MN strain (MNgp120) and synthetic V3 loop peptides as measured by surface plasmon resonance using the BIAcore instrument (Pharmacia Biosensor). VHCDR3 was modified using synthetic oligonucleotides and several clones with reduced koff identified, a number of different substitutions occurring at a single residue position. The residues in the heavy chain identified as reducing koff were simultaneously randomised by site-directed mutagenesis, resulting in scFv variants with koff slowed up to sevenfold. Far from compromising recognition of variant loops, binding to these sequences was improved; the koff from synthetic peptides modelled on V3 loop variants being slowed to a degree similar to that observed with MNgp120. All four changes were located towards either extremes of CDRs 2 and 3, suggesting that the mechanism of improvement may be one of alternation of loop conformation. This work illustrates that phage display can be used to tailor the properties of a therapeutic monoclonal antibody in a predefined fashion.

Amino Acid Sequence

[Trigger thumb in the child].

The trigger thumb is a quite frequent finding in the adult woman over 50 years. In newly born and small children we do, however, also occasionally observe trigger thumbs. As even pediatric specialists are not necessarily familiar with this diagnosis, they tend to refer these small patients as emergencies for acute distortions or subluxations. We describe the clinical findings and therapy for trigger thumb in the child and our own results in comparison with the literature. Except in the small child under six months, who displays a spontaneous recovery in about 30% of the cases, early surgical release of the pulley is the treatment of choice.

Adult

[Smoking cessation at work exemplified by "action blanca casa", a project for smoking cessation in the D. Swarovski & Co., Wattens, firm].

Recent studies about the efficacy of smoking cessation programs in the workplace have brought up to common difficulties. Only long-term-programs show remarkable effects on smoking habits of the workers. Presenting ongoing long-term strategies for open discussion can improve the design of more powerful cessation programs in the future. Our program as an important part of modern "human resources management" is demonstrated and the results after 18 months are discussed.

Adult

The influence of different amounts of n-3 polyunsaturated fatty acids on bleeding time and in vivo vascular reactivity.

Mesenteric bleeding time, mesenteric vascular reactivity, platelet and erythrocyte lipid fatty acid composition were measured at 2-3 weeks, 5-6 weeks and 11-22 weeks in normotensive Wistar rats, fed on high (6.5% energy) or moderate (1.6% energy) intakes of eicosapentaenoic acid (20:5n-3; EPA) as fish oil, compared with controls fed on a diet devoid of EPA. All diets contained the same level of linoleic acid (4% energy): the moderate- and high-EPA diets also contained 1.1 and 4.4% of the energy as docosahexaenoic acid (22:6n-3) respectively. Moderate, but not high, intakes of EPA increased mesenteric bleeding time. Similar reductions in erythrocyte and platelet arachidonic acid (20:4n-6) occurred in animals fed on either high or low amounts of EPA, but the proportion of EPA increased dose-dependently. At high intakes of EPA the proportion of oleic acid in platelets and erythrocytes was decreased. Blood pressure platelet counts, mesenteric vessel diameter and mesenteric vascular reactivity to vasopressin were unaffected by treatment. High intakes of fish oil led to a slight fall in packed cell volume. In a second experiment bleeding time and mesenteric vascular reactivity to noradrenaline were increased 2-4 weeks after receiving a moderate intake of EPA and these effects persisted 5-21 d after switching to a control diet. A similar increase in vascular reactivity to noradrenaline was observed in animals given indomethacin (6 mg/kg) but not in those given aspirin (20 mg/kg).

Animals

Identification of multiple repeat sequences and transcription-related elements within introns 4, 8 and 9 of human Raf-1.

Oncogenic activation of the human c-raf-1 protein (Raf-1) occurs by truncation of its aminoterminus (regulatory domain) and retention of the carboxyterminus (kinase domain). To gain insight into the structure of human raf-1 genomic DNA corresponding to the regulatory domain of Raf-1, we analyzed the nucleotide sequences of introns 4, 8, and 9. Very high frequencies of the direct and indirect repeats, and A/T nucleotides were observed within introns 4, 8, and 9; and the DNA sequences, 5'-TTAGTCA-3' and 5'-TGATTCA-3', like the DNA recognition site of transcription factor AP-1, were identified within intron 4 of raf-1 in human normal and tumor DNAs. In addition, several transcriptional elements (CAAT box, TATA sequences, eukaryotic transcription initiation sites, and cellular transcriptional elements) were found within introns 4, 8, and 9 of human raf-1. These data suggest: 1) the high frequency of intron-specific repeats is a possible recombinational mechanism for derivation of truncated oncogenic forms of Raf-1; and 2) the multiple transcriptional elements within introns 4, 8, and 9 may have important implications in the regulation of raf-1 transcription and, therefore, its role in cell growth and proliferation.

Base Sequence

[Distal radius fractures: conservative or surgical treatment?].

The "classical" Colles fracture of the distal radius is the most common fracture in the adult. In order to reduce the still rather high rate of permanent disability, this fracture involving a functionally important joint requires accurate reduction. The AO-fracture classification introduced by Müller not only defines the severity of an injury, but also allows for decision-making as to the most adequate treatment. Besides the purely conservative management by closed reduction and plaster cast for the type-A fractures, we have a number of other treatment modalities for the more complex-B and C-type fractures, such as closed reduction and percutaneous K-wire application or the use of the small external fixator as well as open reduction and internal fixation by plates and screws for a few selected indications.

Adolescent

[Temporary balloon catheter occlusion for control of bleeding of a blunt injury of the proximal axillary artery. Case report and review of the literature].

We describe the successful placement of an intra-arterial balloon catheter by a femoral approach in order to occlude the proximal arterial end and to control massive bleeding in a patient with rupture of the left axillary artery after blunt scapulo-thoracic dissociation. To our knowledge this technique has so far not been reported in Europe. It allows rapid control of bleeding, minimizes blood loss and markedly facilitates pre- and perioperative management in selected cases. The authors review the relevant literature dealing with this topic.

Adult

[Ambulatory hand surgery].

The majority of surgical interventions about the hand can be done on an outpatient basis and in private practice; however, the surgeon must be well-trained in hand surgery and should master all forms of local and regional anesthesia, permitting an atraumatic technique. In addition, he must be prepared to handle any peri- and intraoperative complication and should be able to refer the patient to a close-by hospital in case of need. Since the aftercare appears to be of paramount importance for a successful outcome, the postoperative rehabilitation must be guaranteed as well. As all these conditions require qualified manpower and a good infrastructure, hand surgery is probably best performed within a small group of practising surgeons.

Ambulatory Surgical Procedures

[Vascular injuries--management in a non-university central hospital].

In a retrospective study the surgically treated vascular injuries (n = 35) of the last 10 years were evaluated. One third of the patients had multiple trauma and in 57% of the cases vascular injury was accompanied by a fracture. All patients (n = 28) except those who underwent delayed amputation (amputation rate 14%) have been followed personally for an average of 5.1 years. 90% of these patients showed an excellent or acceptable longtime result in regard to vascularity, nobody complained of claudication. Diagnosis of a vascular injury was mostly confirmed by direct surgical exploration, only one third of the lesions were diagnosed by arteriogram. A positive signal in Doppler examination does not exclude vascular injury and therefore cannot replace arteriography or exact clinical evaluation.

Adult

Management of displaced supracondylar fractures of the humerus in children.

A series of 33 children with displaced supracondylar fractures of the humerus (SFH) were all treated operatively by open reduction and internal fixation or by closed reduction and percutaneous pinning. A follow-up study was performed on average 29 months (range 3-63 months) after the injury. In 18 per cent of cases primary neurovascular injury was observed and confirmed at operation. Of these patients 32 had open reduction and internal fixation by K-wires; in only one case was closed reduction and percutaneous pinning attempted. If there was preoperative neurological deficit, the nerves were visualized; however nerve suture was not required in our series. In one case we had to reconstruct both the brachial and radial arteries because of intimal lesions totally occluding the vessels. The average hospital stay was 9 days, including pin removal, which was usually performed about 4-5 weeks later, at the time of plaster removal. By Innocenti's criteria, 27 of 30 patients reviewed had an excellent result; three had a good result and three patients were lost to follow-up. There were no complications due to the operation, such as wound healing problems, infections or nerve lesions. In the light of our experience and of the good results, we recommend that displaced SFH be managed by open reduction and internal K-wire fixation. Percutaneous pinning is a good alternative method when closed reduction is successful at the first attempt.

Bone Nails

[Infection of the hand: a specific disease picture].

Certain anatomical and physiological features are responsible for the specific clinical presentations of hand infections: The dorsum of the hand possesses a loose mobile areolar layer, whereas the gripping function of the palm has determined the development of a dense, firmly anchored sheet layer of connective tissue. It follows that infections of the dorsum of the hand can spread easily and give rise to extensive cellulitis. This cannot occur on the palmar aspect, where infection always tracks along the path of least resistance into the deep tissues, rapidly reaching the functionally important structures of the flexor compartments, including the subfascial compartments of the deep palmar space and the space of Parona in the forearm. A similar chain of events characterizes infections of the thenar and hypothenar eminences. Distal finger infections around the nail are a separate clinical entity with a considerable risk of running a chronic course and involving bone or the distal interphalangeal joint. In this case the sequence leads form subcutaneous infection or paronychia via bone infection to joint sepsis. There is considerable scope for misdiagnosis of hand infections, and inappropriate conclusions may lead to serious consequences for future function of the hand. The treatment of hand infections is demanding, time-consuming and not infrequently requires the infrastructure of a hospital clinic; therefore, in cases of doubt, early referral is always advisable.

Bacterial Infections

[Abdominal tuberculosis and open lung tuberculosis caused by mycobacterium bovis].

Abdominal tuberculosis is a rare disease in Western countries and remains difficult to diagnose. The most frequent symptoms are abdominal pain, weight loss, fever, vomiting, constipation and/or diarrhea. Clinical findings include abdominal tenderness, a palpable mass (often in the right fossa due to ileocecal infection), paleness, cachexia and ascites. Suggested radiological investigations include plain abdominal film, upper GI-series and barium enema. Chest X-rays often show signs of either active or inactive tuberculosis. Sputum and gastric juice should be cultured. Coloscopy serves to sample specimens for histology and bacteriology and may help to confirm the diagnosis, which is, however, not ruled out by negative findings. The same holds good for peritoneal biopsy and laparoscopy. Bowel perforation and ileus are frequent complications and always require surgery, whereas uncomplicated cases can be treated by drugs only.

Adolescent

Malignant transformation of human bladder epithelial cells by DNA transfection with the v-raf oncogene.

Transfection of the v-raf oncogene into immortalized, nontumorigenic human bladder epithelial cells resulted in the isolation of two tumorigenic transformants. Both were identified as human and of the same origin as the parent cell line by human leukocyte antigen typing and Southern blot analysis. Both the primary tumorigenic transfectants and the cell lines established from the induced tumors expressed v-raf mRNA and v-raf protein. In both tumorigenic transformants the level of c-myc mRNA was enhanced compared with that of the parent cell line.

Animals