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Biomedical subjects

C G Clark

Publications and source records attributed to C G Clark.

At least 73 records · Page 4Linked to original sources

Vertical banded gastroplasty in the treatment of morbid obesity: results of three year follow up.

Vertical banded gastroplasty has replaced jejunoileal bypass in the surgical treatment of morbid obesity. Although this procedure carries a low incidence of early postoperative complications there is little information on either longer term follow up or the impact on nutritional status. The present study describes the outcome in 42 patients with morbid obesity who underwent vertical banded gastroplasty and were followed up in a special nutrition clinic between nine and 36 months postoperatively. Body mass index (BMI) fell from a preoperative value of 47.4 (6.7) kg/m2 (mean (SD] to 37.5 (5.8), 35 (6.2), 33.9 (6.1), and 33.1 (5.7) kg/m2 at 6, 12, 24, and 36 months respectively. Immediate postoperative complications were minimal but during follow up four patients developed stenosis of the gastroplasty stoma and required reoperation. Plasma albumen concentrations were maintained but three patients developed iron deficiency anaemia. Most patients were able to eat a normal diet in reduced quantities and noted a marked improvement in the quality of life. The benefits and safety of vertical banded gastroplasty suggest an important role for this operation in the management of morbid obesity.

Adult↗

The protective effect of Meciadanol (O-methyl-3(+)-catechin) on experimental ulceration.

Meciadanol, (O-methyl-3(+)-catechin), a histidine decarboxylase inhibitor was shown to have a marked protective action against experimental peptic ulceration in three rat models. The three methods used to induce ulceration were the instillation of absolute alcohol, pyloric ligation following an ulcerogenic South Indian diet and the instillation of rice bran oil into the stomach after pyloric ligation. Meciadanol was shown to reduce incidence, numbers and areas of ulceration and protected mast cells against degranulation and to preserve a normal vascular patterns. Furthermore, Meciadanol reduced gastric acid output and concentration in the pylorus ligation model. These results indicate that Meciadanol may be useful for the treatment of peptic ulcers in humans.

Animals↗

A comparison of carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) in human colorectal cancer.

The development of monoclonal antibodies (MAbs) to tumour-associated antigens has allowed the successful radioimmunolocalization of a variety of tumours and has provided a basis for targeted therapy. In patients with colorectal cancer, antibodies to CEA have been the most widely used for imaging, but their role in targeted therapy may be inhibited by their reaction with normal tissues and with circulating CEA. Epithelial-membrane antigen (EMA) is expressed by most epithelial tumours, including colorectal cancers, and antibodies to EMA may provide a satisfactory alternative. We therefore compared two high-affinity MAbs, one to CEA (C46) and one to EMA (ICR2), in tissues obtained from 31 patients with cancer (18 primary colonic, 6 nodal metastases and 7 liver metastases), 14 patients with adenomatous polyps and 17 with normal colon. The indirect immunoperoxidase staining reaction was used and the results classified as either positive or negative. A heterogeneous pattern of staining was found for both antibodies. ICR2, the anti-EMA, reacted with slightly fewer colonic cancers than C46, the anti-CEA antibody (83% vs. 100%) and a similar number of metastases. Most noticeable was the minimal reaction of anti-EMA with normal colon (12% vs. 71%) and benign polyps (7% vs. 79%) in comparison to anti-CEA. This would suggest a possible role for ICR2 in the radioimmunolocalization and targeting of colorectal cancer.

Antigens, Neoplasm↗

The strength, contractile properties and radiological density of skeletal muscle before and 1 year after gastroplasty.

1. Skeletal muscle strength, contractile properties and radiological composition have been studied in seven morbidly obese adults (six female) before and 1 year after gastroplasty operations. The mean body weight fell from 138.3 kg (SD 25.2) to 99.7 kg (SD 23.0) (P less than 0.001). 2. The strength and contractile properties (force/frequency, relaxation rate and fatiguability) of both the adductor pollicis and quadriceps muscles were unaffected by the weight loss. 3. Computerized axial tomography scans obtained 1 year after surgery showed that the quadriceps contained an abnormally high proportion of fat. The mean fat content was 10.8% (range 3.0-30.1%) compared with 1.6% (range 0-5%) for normal muscle. Two individuals were scanned before and after surgery and the fat content of their quadriceps fell from 12.6% and 6.9% to 3.1% and 3.0%, respectively. 4. It is concluded that in obese individuals large amounts of weight can be lost, from both subcutaneous and intramuscular fat stores, without compromising either the strength or contractile properties of skeletal muscles. These results do not support the claim that skeletal muscle contractility is a sensitive indicator of changes in nutritional status.

Adult↗

Circular ribosomal RNA genes are a general feature of schizopyrenid amoebae.

We have recently shown that the ribosomal RNA genes of the amoebo-flagellate Naegleria gruberi Schardinger, 1899, strain NEG-M are carried exclusively on a 14 kilobasepair plasmid. To explore the distribution of this unique gene arrangement, we have examined another strain of N. gruberi and four other species from the order Schizopyrenida. All have this unusual gene arrangement although the size of the plasmid varies widely. Species groups based on morphological criteria do not agree with those resulting from comparison of plasmid restriction enzyme patterns.

Amoeba↗

Endogenous prostaglandin E2 synthesis preserved following cytoprotection by Roter (bismuth subnitrate) in the rat alcohol model of gastric ulceration.

The protective effect of the compound preparation Roter, principally bismuth subnitrate and the other base constituents of these tablets, magnesium carbonate and sodium bicarbonate, were assessed using the standard alcohol model of gastric ulceration in the rat. Groups of ten rats were studied with Group A as controls, Group B alcohol alone, Group C pretreatment with base components followed by alcohol, Group D pretreatment with bismuth subnitrate followed by alcohol and Group E pretreatment with full formulation Roter followed by alcohol. The study was assessed by measurement of areas of gastric ulceration and tissue prostaglandin E2 (PGE2) levels. Alcohol alone caused gross ulceration and reduction in PGE2 synthesis compared to controls (P less than 0.001). Pretreatment with tablet base gave only marginal protection whilst bismuth subnitrate gave marked protection against ulceration compared to alcohol alone (P less than 0.001). Full formulation Roter also gave marked protection against ulceration compared to alcohol alone (P less than 0.001) and this was associated with PGE2 synthesis indistinguishable from controls but significantly greater than in the alcohol alone group (P less than 0.001). It was not possible to determine whether the normal PGE2 synthesis was the cause or the result of protective effect of Roter and the accompanying reduction in ulceration. It was possible however to conclude that using this model of experimental ulceration. Roter and bismuth subnitrate are 'cytoprotective' and this was associated with the preservation of normal prostaglandin synthesis.

Animals↗

Precise identification of cleavage sites involved in the unusual processing of trypanosome ribosomal RNA.

The large subunit ribosomal RNA (LSRNA) of Trypanosoma brucei is unusual in being cleaved at multiple sites to yield six stable fragments of RNA. We report here the complete nucleotide sequence of two regions of the ribosomal DNA repeat unit. The first sequence includes all of the processing sites involved in the generation of one of the small LSRNA fragments. The second region encodes the trypanosome 5.8 S RNA. By RNA sequencing and S1 nuclease mapping, we have identified the processing sites involved in the generation of both of these small RNAs. On the basis of predicted secondary structure models, we infer that all the cleavages apparently occur near the junction of single- and double-stranded regions. The sites involved in the novel LSRNA processing show a clear symmetry with respect to a conserved region of ten base-pairs. No such signals are evident for the processing sites that generate the 5.8 S RNA.

Animals↗

On the evolution of ribosomal RNA.

Despite the availability of a rapidly growing ribosomal RNA database that now includes organisms in all three primary lines of descent (eubacteria, archaebacteria, and eukaryotes), theoretical treatment of the evolution of the ribosomal RNAs has lagged behind that of the protein genes. In this paper a theory is developed that applies current views of protein gene evolution to the ribosomal RNAs. The major topics addressed are the variability in size, gene arrangement, and processing of the rRNAs among the three primary lines of descent. Among the conclusions are that the rRNAs of eukaryotes retain some primitive features that were probably present in the rRNAs of the earliest cell (the progenote) and that the genes coding for the three major rRNA species were probably originally unlinked.

Animals↗

Photodynamic therapy in the normal rat colon with phthalocyanine sensitisation.

Photodynamic therapy (PDT) involves the interaction of light with an administered photosensitising agent to produce cellular destruction. It has promising potential for the local and endoscopic treatment of gastrointestinal cancer. There is however little data on the response of normal intestine to PDT. We have investigated the use of a new photosensitiser chloro aluminum sulphonated phthalocyanine (AlSPc) for colonic PDT. The peak concentration of AlSPc in the colon measured by alkali extraction occurred 1 h after i.v. injection. The cellular uptake demonstrated by laser fluorescence microscopy was greater in the mucosa than in the muscle. AlSPc was activated in the tissues by light from an argon ion pumped dye laser at 675 nm. The laser power was set at 100 mW and the fibre placed touching the mucosa. In control animals no macroscopic damage was seen. Temperature measurement using a microthermocouple array showed no temperature rise during light exposure. The energy (fluence), dose of sensitiser and time from sensitisation to phototherapy were altered and the area of necrosis measured. The geometry of the colon made theoretical analysis of the correlation between laser energy and size of lesion difficult. However, following direct measurement of the relative light intensity (fluence rate) in the colon we were able to confirm that there was a threshold fluence for colonic necrosis. The area of photodynamic damage seen 72 h after phototherapy fell with the fall in tissue concentration of AlSPc from 1 h to 1 month after i.v. injection. However, maximum tissue necrosis occurred when treatment was performed immediately after i.v. injection. In this situation, intense vascular spasm was seen and any light transmitted through the colon which fell on the small bowel mesentery caused a lethal ischaemic necrosis. The initial histological changes after PDT were vascular, followed by full thickness necrosis at 72 h. Healing by regeneration was complete by 2-3 weeks. Despite full thickness necrosis there was no reduction in the colonic bursting pressure at any time. Colon treated by hyperthermia had a reduced bursting pressure. Specific collagen stains showed that PDT did not alter the submucosal collagen architecture whereas hyperthermia did.

Animals↗

The ulcerogenic and protective action of rice and rice fractions in experimental peptic ulceration.

The ulcerogenic and protective effects of various rice fractions in the diet were studied in the pylorus ligated ulcer model in the rat. Oil present in rice and particularly rice bran becomes ulcerogenic on storage and in this model results in a significant increase in the median (range) numbers of ulcers from six (one to ten) to nine (six to 15) (P less than 0.05). The ulcerogenic effect of stored rice bran oil was reversed by cysteine which significantly reduced the ulcer incidence from 100% to 60% (P less than 0.005) and the numbers of ulcers from 26 (six to 70) to one (zero to four) (P less than 0.001). Fresh rice bran significantly reduced the numbers of ulcers from six (one to ten) to one (one to four) (P less than 0.05). Similarly, unmilled rice and freshly milled newly harvested rice was also shown to be protective in this model by significantly reducing the ulcer incidence from 87.5% to 50% and 0% respectively (P values less than 0.025) and the numbers of ulcers from three (zero to 17) to one (zero to one) and zero (zero to zero) respectively (P values less than 0.001). These results could in part explain the geographical distribution of duodenal ulceration, where the incidence is high in all the rice eating areas of the world, and provide a plausible hypothesis to explain the mechanism of dietary ulcerogenesis.

Animals↗

rRNA genes of Naegleria gruberi are carried exclusively on a 14-kilobase-pair plasmid.

An extrachromosomal DNA was discovered in Naegleria gruberi. The 3,000 to 5,000 copies per cell of this 14-kilobase-pair circular plasmid carry all the 18S, 28S, and 5.8S rRNA genes. The presence of the ribosomal DNA of an organism exclusively on a circular extrachromosomal element is without precedent, and Naegleria is only the third eucaryotic genus in which a nuclear plasmid DNA has been found.

Animals↗

Endoscopic laser palliation for advanced malignant dysphagia.

Palliative treatment of malignant dysphagia aims to optimise swallowing for the maximum time possible with the minimum of general distress to these seriously ill patients. Thirty four patients considered unsuitable for surgery because of advanced malignancy, other major pathology or in whom previous surgery had been unsuccessful were treated endoscopically with the Nd YAG laser. Significant improvement was achieved in 29 (85%). On a scale of 0-4 (0 = normal swallowing; 4 = dysphagia for all fluids), mean improvement was 1.7, with 25 patients (74%) able to swallow most, or all solids after treatment. With increasing experience, the average number of treatment sessions required for each patient became less; initial time in hospital became comparable to that needed for intubation. Failures were caused by inappropriate patient selection (3), or laser related perforation (2). The mean survival in the whole group was 19 weeks (range 2-44). Eighteen patients needed further treatment for recurrent dysphagia, a mean of six weeks (range 2-15) after initial therapy. Ten of these responded, but eight eventually required insertion of a prosthetic tube. The duration of good palliation was very variable after initial laser therapy.

Aged↗

Skeletal muscle function after major abdominal surgery.

The contractile properties of the adductor pollicis and quadriceps muscles have been studied before and 4 and 10 d after major abdominal surgery in 15 patients. Eight patients were considered well nourished and 7 malnourished on the grounds of body mass index, recent weight loss and serum albumin. There were no significant changes in the contractility of the adductor pollicis at 4 and 10 d post-operatively compared to pre-operative values. The only change in the quadriceps was seen in the malnourished patients and was a potentiation of the force:frequency relationship at day 4, affecting force generation at 1 Hz. There was a tendency for the malnourished patients to generate higher forces at low stimulation frequencies and to have slower relaxation rates, but there was no significant difference between the two groups. Pre-operative contractile properties of those patients who developed post-operative complications were not different from those who were free of complications, nor did the post-operative results of the two groups of patients differ. The patients generated higher forces at lower stimulation frequencies than is usually found in young normal subjects. This may be due to age, disease or nutritional factors, but it is not possible to determine the relative contributions of these factors from this study.

Abdomen↗