APC mutation and tumour budding in colorectal cancer

AIM: To determine the frequency of tumour budding and somatic APC mutation in a series of colorectal cancers stratified according to DNA microsatellite instability (MSI) status. Material/Methods: Ninety five colorectal cancers were genotyped for APC mutation in the mutation cluster region (exon 15) and scored for the presence of tumour budding at the invasive margin in haematoxylin and eosin stained sections. A subset was immunostained for beta catenin and p16. RESULTS: The frequency of both somatic APC mutation and tumour budding increased pari passu in cancers stratified as sporadic MSI high (MSI-H), hereditary non-polyposis colorectal cancer (HNPCC), MSI low (MSI-L), and microsatellite stable (MSS). Both budding and APC mutation were significantly less frequent in sporadic MSI-H cancers than in MSI-L or MSS cancers. Tumour buds were characterised by increased immunostaining for both beta catenin and p16. CONCLUSION: Tumour budding is associated with an adverse prognosis. The lack of budding in MSI-H colorectal cancer may account for the improved prognosis of this subset and may be explained by an intact WNT signalling pathway and/or inactivated p16(INK4a).     

Inhibition of sodium transport by angiotensin II in the main duct of the rabbit mandibular gland isolated and perfused in vitro

Summary The effect of angiotensin II on nett electrolyte transport by the main duct of the rabbit mandibular gland was investigated in vitro using a perfused duct preparation bathed in a Haemaccel^®-nutrient salt solution. In a bath concentration of 4×10^–10 M, angiotensin reduced nett absorption of Na⁺ and Cl^– by about 8% and depolarized the transepithelial electrical potential difference (P.D.) by about 13%; the drug had no effect on ductal transport of K⁺ and HCO ₃ ^– . In both lower (4×10^–11 M) and higher (4×10^–9 M) concentrations, angiotensin had qualitatively similar effects. After exposure to the hormone for about 30 min, Na⁺ transport and P.D. became unstable and gradually fell away towards zero. It is concluded that angiotensin in physiological concentrations has a specific inhibitory effect on Na⁺ absorption by salivary duct cells which could arise either from a change in the Na⁺ pump rate or from a conductance change in the apical or basal membrane of the epithelial cell.     

Platelet aggregation in chronic idiopathic thrombocytopenic purpura.

A method for washing platelets by albumin density gradient separation has been modified to prepare platelet rich plasma of thrombocytopenic patients for platelet aggregation studies. The concentration procedure, consisting of centrifuging platelets into a specific gravity gradient between plasma and 40-45% aqueous solution of bovine albumin, does not affect platelet aggregation adversely. Platelet aggregation in eight patients with chronic idiopathic thrombocytopenic purpura was determined by this method. On the basis of the results the patients could clearly be divided into two groups: four patients with normal aggregation and four with a qualitative platelet defect. In contrast to the other patients, the group with an in vitro platelet functional defect all had more prolonged bleeding times and the presence of a serum antiplatelet antibody.     

Variable region correlates of group b allotypes: amino acid sequence studies of b9 L chains from homogeneous antibodies.

The amino acid sequence was determined for residues for residues 1 to 88 and residues 110 to 147 for a rabbit light chain (4153-I) with allotype b9 from a homogeneous anti-streptococcal antibody. The amino acid sequence of the L chain from a second antibody (4153-II) was also determined for residues 1 to 49 and 62 to 77. In spite of the large differences in constant region sequence between b4 and b9 L chains, the variable regions of these antibodies are quite similar to those reported for b4 L chains. Both chains bear a b9-specific substitution (glutamic acid) at position 16. The 4153-I chain also has substitutions at positions 70 and 81 that may be exclusive to variable regions of the L chains with the b9 allotype. These allotype-associated VL structural differences offer support to the notion that structural genes for the CL region are either linked to distinct VL gene complexes or that certain V regions are expressed only in concert with certain CL regions.     

Further assessment of the effects of occupational radiation exposure in the United Kingdom Atomic Energy Authority mortality study

The United Kingdom Atomic Energy Authority mortality study was designed to investigate the relation between exposure to ionising radiation and mortality among the authority's employees. The present paper describes some of the problems encountered in assessing occupational exposure to low dose radiation and examines whether the study's conclusions about the relation between exposure and mortality could be affected by the methods used. The study covered the years 1946 to 1979 during which time the frequency with which personal film dosimeters were issued changed from weekly to monthly, and the threshold level below which measurements were not made decreased 20-fold. Exposure from "below threshold" readings made an important contribution to total exposure in the early years. Estimates, based on the remeasurement of a sample of old films, indicated that the average whole body exposure before 1961 may have been about double that which was measured. Furthermore, although records were kept of when dosimeters were lost or damaged, the associated exposures were unknown and could only be estimated. Workers whose dosimeter readings were missing for more than 5% of the time during which they were monitored had higher all cause mortality (p = 0.04) and higher mortality from accidents and violence (p = 0.05) than other radiation workers. The results of analyses of mortality in relation to whole body exposure were compared when the exposures included estimates of the below threshold and missing exposures and when these exposures were assumed to be zero. Some of the findings differed, but none changed sufficiently to alter the general conclusions. Although the trend in mortality from all cancers changed from one in which the increase with exposure was far from statistically significant (p = 0.3) when the below threshold and missing values were assumed to be zero to one that approached significance (p = 0.06) after they were estimated, calculations of the annual excess deaths from cancer per unit dose resulted in broadly similar estimates. Studies of workers exposed to ionising radiation usually focus on mortality in relation to whole body exposure. In the present paper its relation to neutron and surface exposure is also examined. Workers with measured neutron exposures had significantly lower all cause mortality than other workers with a radiation record (p = 0.03). Surface exposure was significantly related to mortality from all cancers (p = 0.02) and prostatic cancer (p less than 0.001). Some data on cancer registration are presented but these cannot be readily interpreted because cancer registration details were available only for ex-employees who may not be typical of the workforce as a whole.     

Clinical evaluation of spinal cord monitoring in scoliosis surgery

The somatosensory evoked potential (SEP) is a technique that can be used to monitor sensory conduction within the spinal cord throughout the course of spinal surgery. The authors describe the technique, stimulation, and recording parameters, which most critically affect the success and reliability of monitoring trials. In addition, we show that in all 40 patients tested fully, the SEP results were in complete agreement with the clinical findings at the time of the wake-up test. In this series, there was no instance of a "false-positive" SEP result, or of the SEP failing to detect neural damage. Temporary, neurologic deficit occurred on two occasions, which are described in detail. These show that the SEP is rapid, enables neurologic complications to be detected at an early stage of surgery, and can identify lateralized problems. It is concluded that the technique may provide a clinically valuable method for continuous and prolonged monitoring of spinal cord function.     

Routine cross-matching is not necessary for a transurethral resection of the prostate

Two hundred and fifty-five consecutive patients undergoing transurethral prostatectomy were studied prospectively to test a policy of not routinely cross-matching blood. Blood was ordered only for patients with anaemia, a major medical risk factor, a prostate gland estimated to be greater than 60 g, or the presence of red cell alloantibodies. Of the 203 patients who were "grouped and saved" only, 30 (12%) were subsequently cross-matched and 22 (8.5%) transfused. There were no significant problems as a result of the operation of this policy. The value of these pre-operative criteria for cross-matching was confirmed, apart from the clinical estimation of prostatic size. The use of such a policy could be of significant value to the hospital blood transfusion services.