Subtype determination of soma-dendritic α2-autoreceptors in slices of rat locus coeruleus

The aim of the study was to subclassify the soma-dendritic α₂-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average rate of 1 Hz. The selective α₂-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential discharge with IC₅₀ values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K _d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K _d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored firing with EC₅₀ values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates – against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even at a concentration of 1 μM. These findings identify the soma-dendritic α₂-autoreceptors of the LC as the rat variant of the α_2A/D-adrenoceptor, i.e. α_2D. Not only presynaptic but also soma-dendritic α₂-autoreceptors may at least predominantly be α_2A/D throughout the nervous system. Received: 3 March 1997 / Accepted: 21 April 1997     

Current perspectives of catabolic mediators of cancer cachexia.

The development of cancer cachexia is perhaps the most common manifestation of advanced malignant diseases and has been recognized as a poor prognostic sign. The abnormalities associated with the condition include progressive weight loss, anorexia, asthenia, and anemia. The degree of cachexia is inversely correlated with the survival time of the patient and always implies a poor prognosis. Currently there is no established mechanism for cancer cachexia, but the severe metabolic disturbances and marked alterations in carbohydrate, lipid, and protein metabolism in the host finally lead to an increased energy deficiency. Weight loss, the key feature of cachexia, is due to a reduction of food intake, an increase in energy expenditure, or a combination of the two. A variety of changes in nutrient metabolism have been described in patients with cancer cachexia. Patients frequently exhibit a relative glucose intolerance and insulin resistance with increased activity of the Cori cycle. The cancer-bearing state affects protein synthesis and breakdown in different tissues of the body in a different manner. An acute-phase protein response can be presented in a significant proportion of patients with cancer with disease progression. A variety of proinflammatory cytokines appears to play a role in aspects of cachexia and a complex network of cytokines in combination with other factors might be involved. Aside from potential humoral mediators of cachexia, tumor-derived biologically active molecules have been reported recently.     

Severely comminuted distal radial fracture as an unsolved problem: complications associated with external fixation and pins and plaster techniques

Seventy-six patients with severely comminuted distal radial fractures were treated at two institutions, of which the overwhelming majority were Frykman class VIII. Fifteen fractures were open. Thirty patients were seen at the University Hospital; 17 had pins and plaster and 13 had external fixation. Forty-six patients were seen at Kaiser Hospital; all had pins and plaster treatment. The complication rate for those with pins and plaster at the University Hospital was 53%; the complication for external fixation rate was 62%. The affiliated-hospital complication rate was 52%. All patients with ipsilateral forearm shaft and carpal fractures developed a nonunion of the carpal fracture. Few patients maintained anatomic reduction, and many had significant intra-articular malalignment. External fixation with threaded half pins did not obviate pin problems in our series. These methods may help manage severely comminuted distal radial fractures, but complications should be anticipated and alternative treatment considered, especially when ipsilateral carpal or forearm shaft fractures are present.     

Acute carpal tunnel syndrome caused by pigmented villonodular synovitis of the wrist

An 89-year-old woman developed an acute carpal tunnel syndrome secondary to hemarthrosis associated with pigmented villonodular synovitis of the wrist. Pigmented villonodular synovitis is rare in a patient of this age and is an unusual cause of carpal tunnel syndrome.     

Comminuted intraarticular fractures of the distal radius

The comminuted intraarticular fracture of the distal radius requires early, accurate reduction of the articular surfaces and sustained restoration of anatomic position. The most commonly employed methods are pins and plaster, external fixation, percutaneous pinning, and open reduction and internal fixation. There are pitfalls, advantages, and disadvantages inherent in each method. Careful preoperative analysis of individual patients and fractures determines the therapeutic options.     

Developments in treatment of primary irresectable rectal cancer

Abstract The treatment options for primary irresectable rectal cancers are discussed. Assessment of tumour stage is the first step for an appropriate choice of treatment. Following a diagnosis of rectal cancer, a vast array of diagnostic procedures is available to determine its stage, and thereby its best treatment options. From the many (new) diagnostic options the merits and drawbacks are discussed. If a diagnosis of irresectability is made, further treatment options should include radiotherapy in most cases, some aspects of timing and application, i.e. intra-operative treatment are discussed. Chemotherapy options are manifold, the results are discussed and some new options are explored.     

Comminuted distal radius fractures.

Comminuted displaced fractures of the distal end of the radius pose a significant treatment challenge. The goal of treatment is to restore functional, painless motion of the wrist and fingers. Although satisfactory results correlate to a large extent with obtaining and maintaining normal anatomy, excessive distraction and a flexed wrist position with external fixation cause more harm than good, even if the anatomy is restored.     

A nationwide evaluation of multiple congenital abnormalities in Hungary

A population-based study of 7,049 index patients with multiple congenital abnormalities (MCA) born in Hungary during 1973-1982 was organized by the Hungarian Center for Congenital Anomaly Control. All clinically recognized syndromes and associations which were submitted (2,049) were accepted without any further follow-up. New or supplementary information was requested in the case of unspecified MCA (320). A copy of detailed necropsy records was requested from pathologists in lethal cases (2,022). Following these steps, apparent but not true instances of MCA were excluded (399), and an attempt was made to assign as many of the remainder as possible in 17 well-delineated MCA entities (900). The living index patients with severe MCA were referred where possible to the regional centers for evaluation (864). One hundred and seventy entities were identified, and seven cases were excluded as not representing MCA. In the so-called 3,393 unidentified cases for which no diagnosis was possible, the component abnormalities were tabulated according to their number. The final count was 6,643 cases with MCA, which is equivalent to a birth prevalence of 4.0 per 1,000 total births, and to 10% of recorded cases with congenital anomalies. As a result of this program the proportion of recognized syndromes and associations among children with MCA increased from 29% to 47%. The accuracy of diagnoses has improved, e.g., the occurrence of unspecified cases decreased from 4.5% to 2%. As a result of this study, the number of chromosomal (1,700), Mendelian (557), and teratogenic (104) syndromes and associations (758) was considerably greater than the initial notifications indicated.