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Biomedical subjects

D Doll

Publications and source records attributed to D Doll.

13 recordsLinked to original sources

Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer.

The gene SASH1 (SAM- and SH3-domain containing 1) has originally been identified as a candidate tumour suppressor gene in breast cancer. SASH1 is a member of the SH3-domain containing expressed in lymphocytes (SLY1) gene family that encodes signal adapter proteins composed of several protein-protein interaction domains. The other members of this family are expressed mainly in haematopoietic cells, whereas SASH1 shows ubiquitous expression. We have used quantitative real-time PCR to investigate the expression of SASH1 in tissue samples from 113 patients with colon carcinoma, and compared the expression with 15 normal colon tissue samples. Moreover, nine benign adenomas and 10 liver metastases were analysed. Expression levels of SASH1 were strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in liver metastases. Moreover, SASH1 was also found to be downregulated on protein levels by immunoblot analysis. However, SASH1 expression was not significantly deregulated in precancerous adenomas and in earlier stage lesions (UICC I). Overall, 48 out of 113 primary colon tumours showed SASH1 expression that was at least 10-fold lower than the levels found in normal colon tissue. Downregulation of SASH1 expression was correlated with the formation of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival. This study demonstrates for the first time that expression of a member of the SLY1-gene family has prognostic significance in human cancer.

Adenoma↗

[Procedures of temporary wall closure in abdominal trauma and sepsis].

Temporary abdominal closure methods differ mainly between vacuum-assisted and conventional approaches. Each method has its indications. Vacuum-assisted methods seem to be superior especially for trauma indications--in terms of lethality, the possibility of secondary closure during primary hospital stay, and frequency of enterocutaneous fistulas. Skin-only closure might be used as a short-term application (e.g. when damage control closure is needed), and the Bogota bag silo gives space to protruding bowels in pending or manifest abdominal compartment syndrome. Temporary fascial mesh closure enables repetitive laparotomies through the mesh, thus sparing the fascia. For that reason it is to be preferred, especially for its good practicability in clinical situations and on mission abroad.

Abdominal Injuries↗

[Penetrating injuries to the pelvis].

As criminality and weapon use increase, general and military surgeons are increasingly confronted with penetrating pelvic injuries both at home and on peacekeeping missions. Penetrating injuries to the iliac vascular axis are associated with considerable mortality, and thus the majority of these emergency patients arrive in a state of deep hypovolemic shock. Concomitant bowel injuries are present in one of five cases, resulting in contamination of the damaged area. Surgical options are simple lateral repair, ligation of the veins, temporary shunt insertion, and prosthetic graft interposition in the injured artery. In extremis ligation of the common or external iliac artery may be the only option to save the patient's life. Surgeons must be aware that damage control surgery and related methods may be needed early on to enable patient survival.

Emergencies↗

[The value of thoracoscopy in thorax trauma].

A hemodynamically stable patient presenting with persistent bleeding through his chest tube (ICD) is a classic indication for early thoracoscopic intervention in trauma. The source of bleeding and air leaks can be identified and often treated: bleeding and perforated pulmonary segments can be resected, and chest wall bleeding may be coagulated or sutured. Injuries to the diaphragm are difficult to diagnose, as they might not be seen in conventional trauma imaging without gross herniation of intra-abdominal contents into the thoracic cavity. Identifying the site of diaphragm perforation can give useful hints in thoracoabdominal trauma, identifying injured cavities and localizing the bullet or stab tract. Most often, diaphragmatic defects may be closed during diagnostic thoracoscopy as well. Non- or partially drainable hemothorax is another indication for thoracoscopy. Coagulated blood can be mechanically mobilised, and aspirated or primary bleeding may be stopped. Effective lavage and a high-performance suction device are required. Correct placement of the drainage is part of optimized therapy, along with inspection of all intrathoracic organs and surfaces. Furthermore, surgical and anaesthesiological teamwork and experience are prerequisites for the fast, professional application of a minimally invasive thoracoscopic approach in chest trauma patients. Diagnostically and theurapeutically, thoracoscopy plays an important role in the trauma setting--in the case of hemodynamically stable patients.

Empyema, Pleural↗

[What to do if incompressible bleeding from a stab wound occurs in EMS and ER? Temporary control with a Foley catheter].

Exsanguination plays a key role in avoidable prehospital deaths. As some bleedings from deep stab wounds cannot be stopped with direct compression, the insertion of a Foley catheter can prevent ongoing bleedings. A case report of bleeding from a stab wound in the supraclavicular region is given. The simple measure of careful insertion and blocking of a Foley catheter proved to be a key resuscitative procedure which can be done under any suitable circumstances.

Adult↗

[German education for treatment of penetrating gut traumata in army service].

On military missions abroad, surgical care for penetrating abdominal injuries differentiates from that given at home. The different conditions in the field usually include a single general surgeon with no further specialists or hospitals to rely upon. Thus a mismatch between treatment capacity and needs can be experienced in mass casualty situations. Therefore the focus is on damage control surgery, getting patients fit for evacuation, and transport home under intensive care if needed. Knowledge of ballistics and explosive devices are adjunct fields of interest, as they improve the understanding and treatment of military injuries. Although these aspects add up to additional training requirements to be met by our surgeons, we are convinced that the new German education standards will allow successful training of future military surgeons.

Abdominal Injuries↗

[Treatment of penetrating injuries of neck, chest and extremities].

Penetrating injuries such as gunshot wounds have traditionally been rare in Europe, with the result that European surgeons have only limited experience in their management. Socio-economic changes in the last decade have led to an increase in the frequency of injuries of this type, partly due to the expansion of organized crime and partly because of involvement of the European military in peace-keeping missions in Europe and elsewhere in the world. The purpose of this article is to offer some guidelines in the management of extremely serious or rarely encountered injuries to the neck, chest and peripheral arteries and discuss controversies and possible future changes in their management as a result of the extensive experience of treating penetrating trauma in our hospital.

Amputation, Surgical↗

Serine/threonine protein phosphatases and synaptic inhibition regulate the expression of cholinergic-dependent plateau potentials.

We previously identified cholinergic-dependent plateau potentials (PPs) in CA1 pyramidal neurons that were intrinsically generated by interplay between voltage-gated calcium entry and a Ca(2+)-activated nonselective cation conductance. In the present study, we examined both the second-messenger pathway and the role of synaptic inhibition in the expression of PPs. The stimulation of m1/m3 cholinergic receptor subtypes and G-proteins were critical for activating PPs because selective receptor antagonists (pirenzepine, hexahydro-sila-difenidol hydrochloride, 4-diphenylacetoxy-N-methylpiperidine methiodide) and intracellular guanosine-5'-O-(2-thiodiphosphate) prevented PP generation in carbachol. Intense synaptic stimulation occasionally activated PPs in the presence of oxytremorine M, a cholinergic agonist with preference for m1/m3 receptors. PPs were consistently activated by synaptic stimulation only when oxytremorine M was combined with antagonists at both GABA(A) and GABA(B) receptors. These latter data indicate an important role for synaptic inhibition in preventing PP generation. Both intrinsically generated and synaptically activated PPs could not be elicited following inhibition of serine/threonine protein phosphatases by calyculin A, okadaic acid, or microcystin-L, suggesting that muscarinic-induced dephosphorylation is necessary for PP generation. PP genesis was also inhibited following irreversible thiophosphorylation by intracellular perfusion with ATP-gamma-S. These data indicate that the expression of cholinergic-dependent PPs requires protein phosphatase-induced dephosphorylation via G-protein-linked m1/m3 receptor(s). Moreover, synaptic inhibition via both GABA(A) and GABA(B) receptors normally prevents the synaptic activation of PPs. Understanding the regulation of PPs should provide clues to the role of this regenerative potential in both normal activity and pathophysiological processes such as epilepsy.

Action Potentials↗

PEDB: the Prostate Expression Database.

The Prostate Expression Database (PEDB) is a curated relational database and suite of analysis tools designed for the study of prostate gene expression in normal and disease states. Expressed Sequence Tags (ESTs) and full-length cDNA sequences derived from more than 40 human prostate cDNA libraries are maintained and represent a wide spectrum of normal and pathological conditions. Detailed library information including tissue source, library construction methods, sequence diversity and abundance are available in a library archive. Prostate ESTs are assembled into distinct species groups using the multiple alignment program CAP2 and are annotated with information from the GenBank, dbEST and Unigene public sequence databases. Annotated sequences in PEDB are searched using the BLAST algorithm. The differential expression of each EST species can be viewed across all libraries using a Virtual Expression Analysis Tool (VEAT), a graphical user interface written in Java for intra- and inter-library species comparisons. PEDB may be accessed via the World Wide Web at http://www.mbt.washington.edu/PEDB/

Base Sequence↗

Carboplatin and vinblastine in advanced non-small-cell lung cancer: a phase II study.

Between July 2, 1987, and August 21, 1987, Cancer and Leukemia Group B (CALGB) conducted a phase II evaluation of carboplatin (CBDCA) and vinblastine (VBL) in advanced non-small-cell lung cancer. Of the 58 patients who entered the study, 55 were eligible and produced follow-up data. Chemotherapy, which was carried out in 28-day cycles, consisted of 4 mg/m2 VBL given on days 1 and 3 and 125 mg/m2 CBDCA given on days 1-3. Partial responses were observed in 10 cases (18%), and 1 patient (2%) exhibited regression of evaluable disease. No complete responses were achieved. The overall objective response rate was 20%. The median survival was 6.1 months, and the median time to treatment failure was 3.3 months. Life-threatening (grade 4) toxicity was mainly leukopenia (20%), followed by anemia (7%), infection (4%), thrombocytopenia (2%), fever (2%), nausea and vomiting (2%), and weight loss (2%). There were two deaths due to infection. The results of this study demonstrate that the combination CBDCA/VBL is active in advanced NSCLC; however, whether this combination is more active than either CBDCA or VBL alone is unknown.

Antineoplastic Combined Chemotherapy Protocols↗