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Biomedical subjects

M E Lambert

Publications and source records attributed to M E Lambert.

At least 19 recordsLinked to original sources
PubMed1991

Endoscopic sphincterotomy: the whole truth.

An 8 year experience of 602 patients (median age 76 years) referred for endoscopic management of common bile stones is reported. No patient referred for treatment has been excluded. A diagnostic cholangiogram was achieved in 94 per cent and sphincterotomy was accomplished in 91.5 per cent. The bile ducts were demonstrated to be completely cleared of stones in 491 (81.6 per cent) of 602 patients. A mean number of 1.9 endoscopic retrograde cholangiopancreatography examinations per patient were necessary to achieve this result. Complications of endoscopic sphincterotomy, which were strictly defined, occurred in 10.5 per cent of patients although five patients had two complications (total complication rate 11.3 per cent). The 30-day mortality rate was 2.2 per cent, seven of 13 deaths (1.2 per cent) occurring as a direct result of sphincterotomy. There have been statistically significant improvements in bile duct clearance and complication rates with increasing experience of endoscopists.

Adolescent↗
PubMed1990

Inducible cellular responses to ultraviolet light irradiation and other mediators of DNA damage in mammalian cells.

Both naturally occurring and carcinogen-induced tumors display not only point mutations in cellular oncogenes but also more complex changes in cellular oncogenes and other cellular genes. For this and other reasons, it seems likely that DNA damage in mammalian cells can induce alterations in gene expression that may have both short and long term consequences in the target cell. The purpose of this review is to summarize current available information on inducible responses to UV-irradiation and other mediators of DNA damage in mammalian cells, and to provide some working hypotheses. We have divided these responses into three time frames, immediate (0-12 hours), early (12-48) and late (beyond 48 hours). Immediate responses include the action of DNA repair enzymes, some of which are induced as a consequence of DNA damage, and transient inhibition of DNA synthesis. Within the past few years considerable evidence has accumulated that during this immediate period there is increased expression of certain cellular oncogenes, proteases and proteins whose functions remain to be identified. It is of interest that the expression of some of these genes is also induced by certain growth factors, tumor promoters and heat shock. Alterations in gene expression during the subsequent "early" period (12-48 hrs.) have not been studied in detail, but it is during this period that one can detect increased replication of several types of viruses in cells that harbor these viruses. We have examined in detail the induction of asynchronous polyoma DNA replication (APR) in a rat fibroblast cell line carrying integrated copies of this DNA. We have obtained evidence that UV-irradiation of these cells leads to the synthesis of a 40 kd protein, within the first 1-24 hrs after irradiation, that binds to a specific sequence TGACAACA in the regulatory region of polyoma DNA. We suggest that this protein acts together with other proteins to induce APR and that this serves as a useful model for understanding the mechanisms responsible for amplification of cellular genes, a phenomenon often seen in malignant tumors. Finally, we discuss how the events occurring during the immediate and early periods following DNA damage might lead to late effects in the target cell that are stable and contribute to the genotype and phenotype of some of the progeny of these cells that are destined to become tumor cells.

Animals↗
PubMed1989

Enhancement of major histocompatibility class I protein synthesis by DNA damage in cultured human fibroblasts and keratinocytes.

Exposure of primary human fibroblasts or simian virus 40-transformed human keratinocytes to several different classes of DNA damage, including UV light C (254 nm), resulted in a rapid increase in the expression of human major histocompatibility class I (MHC-I) proteins. MHC-I induction was also detected after exposure to low doses of the protein synthesis inhibitor cycloheximide, suggesting that MHC-I induction by DNA damage may be a component in a derepressible cellular SOS pathway.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1988

Endoscopic removal of retained stones after biliary surgery.

Seventy-three patients with retained stones in the common duct after biliary surgery underwent attempted endoscopic removal at a mean interval of 39 days after surgery. Endoscopic extraction was successful in 63 patients (86 per cent). Complications occurred in 14 patients (19 per cent). The most frequent complication was haemorrhage which occurred in nine patients, four of whom required surgery; two other patients required surgery for complications. The complication rate of endoscopic sphincterotomy in recently operated patients may be higher than in the non-operated patient. Less invasive methods, such as dissolution therapy or T tube track extraction, may be preferable as they are associated with less risk. Endoscopic sphincterotomy should be reserved for patients in whom these alternative techniques fail or are inappropriate.

Aged↗
PubMed1988

Distribution of the c-myc oncoprotein in normal and neoplastic tissues of the rat colon.

A rat model of 5-azoxymethane induced colon cancer was studied in order to correlate histopathological changes and the differential distribution of the c-myc protein. Weanling Fisher 344 rats were injected with three, one week apart, subcutaneous injections of 5-azoxymethane (AOM) (15 mg kg-1) and the animals were divided into low and high fat diet groups. Nine colon tumors, of varying degrees of malignancy, that developed in the AOM-treated rats, and sections of normal colonic mucosa were examined. A rabbit polyclonal anti-c-myc antibody produced nuclear staining at 1:100 dilution in cryostat frozen sections of the normal rat colonic mucosa and the colon tumors when prepared with a Cryostat Frozen Sectioning Aid (CFSA). The tissue localization of the c-myc antibody staining revealed: (1) in normal mucosa, nuclei of the basal portion of the mucosa; (2) in adenomatous polyps, nuclei at all levels of the mucosa; and (3) in a carcinoma in situ, intense staining of glandular epithelial cell nuclei at all levels within the tumor. This procedure may provide a sensitive method for detecting abnormal cells in the colonic epithelium that have an altered proliferative capacity.

Animals↗
PubMed1987

Induction of asynchronous replication of polyoma DNA in rat cells by ultraviolet irradiation and the effects of various inhibitors.

The ability of various DNA damaging agents to induce asynchronous replication of polyoma DNA (APR) in rat cells carrying integrated copies of these DNA sequences may provide a useful model for understanding mechanisms of gene amplification. The present study has explored in detail the ability of UV irradiation to induce APR in the polyoma transformed rat fibroblast cell line H3. We have found that the optimum condition for induction of APR was obtained by irradiating the H3 cells with UV-C (wavelength, 254 nm) at 1-2 J/m2. Irradiation with UV-B (270-360 nm) was much less effective, and no induction of APR was obtained with even high doses of UV-A (345-440 nm). This action spectrum provides evidence that the critical target for induction of APR is DNA. We found that when normal rat fibroblasts were irradiated with UV-C and then fused to H3 cells, this also led to induction of APR. These results provide evidence that the induction of APR by UV-C is mediated by a trans-acting factor. The induction of APR by UV-C was inhibited by high doses of cycloheximide or actinomycin D, suggesting that the production of this trans-acting factor requires de novo protein and RNA synthesis. On the other hand, low doses of cycloheximide or actinomycin D alone were able to induce APR, perhaps by blocking the synthesis of cellular factors that normally inhibit APR. Thus, induction of APR by UV-C provides a useful system for identifying cellular factors that might mediate or prevent the asynchronous replication of various DNA sequences.

Animals↗
PubMed1987

A computer simulation for behavior therapy training.

Computer simulation technology has been applied to a wide variety of learning tasks; however, behavior therapy training has not been among them. A computer simulation has recently been developed for use in behavior therapy training. The simulation written for Apple II microcomputers reflects possible referral, assessment, and intervention procedures encountered by a behavior therapist in a mental health center. Forty-two pieces of assessment information may be drawn from 8 general areas, while 6 different interventions may be chosen after a diagnosis is reached. Simulation content and utility were rated highly by both practicing behavior therapists and trainees.

Behavior Therapy↗
PubMed1987

Nitropyrenes are inducers of polyoma viral DNA synthesis.

The biological activity of a series of nitropyrenes was assayed by measuring their ability to induce the asynchronous replication of viral DNA in rat fibroblasts transformed by a ts-a mutant of polyoma virus. Concentrations of 10-30 micrograms/ml of 1-nitropyrene (1-NP) induced viral replication, and this effect was enhanced by addition of rat-liver S9 microsomal fraction (300 micrograms/ml) to the culture medium. The response was less than that obtained with 0.1 micrograms/ml of the activated metabolite of benzo[a]pyrene (BP), BP trans-7,8-dihydrodiol-9,10 epoxide (anti) (BPDE). A series of di-, tri-, and tetra-nitropyrenes were also found to induce polyoma DNA replication, in the absence of exogenous microsomal activation, displaying strongly positive effects at 0.5-2.0 microgram/ml. Dose-response curves with 1,6-dinitropyrene (1,6-DNP) from 0.01 to 0.5 microgram/ml indicated that this compound was approximately equipotent with BPDE for induction of polyoma DNA synthesis. Studies of drug metabolism, DNA binding and DNA adduct formation indicate that 1,6-DNP is metabolized in this cell line, binds to DNA, and forms stable adducts. The level of DNA modification seen with 1,6-DNP is higher than that observed under comparable conditions with an equivalent dose of BPDE. These findings provide additional evidence that the nitropyrene class of compounds can exert biological effects in mammalian cells, and that the dinitropyrenes are more potent than 1-NP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1986

Mammillary fistula.

During a 6-year period 38 patients with 52 mammillary fistulae were seen. On average, 5 abscesses had preceded recognition of a fistula in the areolar region (range 1-18). In 11 cases the fistulae were immediately apparent as discharging openings but they more commonly presented as subareolar abscesses. Fistulae were treated either by laying open or by excision of the track and at mean follow-up of 25 months (range 1-75) there has been recurrent fistula formation in only one case. Mammillary fistulae should be suspected and sought in all patients presenting with abscesses adjacent to the nipple.

Abscess↗
PubMed1986

Management of the septic complications of diverticular disease.

One hundred and five patients underwent surgical treatment of septic complications of diverticular disease. In nine cases, operation was carried out for acute large bowel obstruction and in the remainder for peritonitis. An inflammatory mass and/or localized abscess was found in 23 cases. Free pus without evidence of 'communicating' perforation was found in a further 33 and 'communicating' perforation in 40. Treatment by primary resection or by transverse colostomy and drainage were both associated with significantly lower mortality from sepsis than treatment by drainage alone. In cases without 'communicating' perforation, there was no difference in mortality between primary resection and transverse colostomy with drainage. Although the advantage of primary resection was most apparent in cases with 'communicating' perforation, it did not reach statistical significance. In three cases treated primarily without resection the pathology was subsequently found to be that of carcinoma. In 'favourable' circumstances, i.e. without 'communicating' perforation, defunctioning colostomy with drainage has an acceptably low mortality rate and may be undertaken by a less experienced surgeon to avoid a difficult resection. Ideally these problems should be dealt with by an experienced surgeon; we prefer to treat the septic complications of diverticular disease by primary resection.

Abscess↗
PubMed1986

Development of a computerized reference retrieval system: a behavior therapy training tool.

The vastness of the behavior therapy literature base often poses problems for beginning therapists who need greater familiarity with assessment and intervention literature. Hence a computerized reference retrieval system was developed for trainees to access behavior therapy references efficiently. The system contains over 1600 references from 158 problem categories and is economically competitive with commercial systems. Similar systems can be established using currently available microcomputer technology. The present system is primarily used by doctoral and masters students to assist in case conceptualizations and decision making during practicum courses.

Behavior Therapy↗
PubMed1986

Carcinogen induced asynchronous replication of polyoma DNA is mediated by a trans-acting factor.

We have demonstrated that carcinogen damage to DNA induces the production of cellular factors that act in trans to enhance the asynchronous replication of polyoma viral DNA. Exposure of a polyoma virus-transformed rat cell line to benzo[a]pyrene-7,8-diol-9,10-oxide (BPDE), the ultimate carcinogenic metabolite of benzo[a]pyrene, led to the accumulation of heterogeneously sized free viral DNA molecules which contain polyoma origin sequences as well as cellular sequences that flank the integrated viral DNA. When the sequence gpt was linked to the polyoma early region and transfected into rat cells, it underwent asynchronous replication in response either to direct treatment of the transfected cells with BPDE, or to fusion of untreated transfected cells with normal cells previously exposed to BPDE. Transient arrest of the cell cycle by hydroxyurea, isoleucine deprivation or methotrexate caused a slight enhancement of viral DNA replication when compared with BPDE. Both aphidicolin, an inhibitor of DNA polymerase alpha, and 3-aminobenzamide, an inhibitor of poly[ADP]ribosyl transferase, caused marked inhibition of BPDE-induced viral DNA synthesis. The induction of a trans-acting factor in response to damage of cellular DNA may be relevant to synergistic interactions between environmental chemicals and DNA viruses in cell transformation and to the general phenomenon of gene amplification.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1979

Campylobacter colitis.

Eleven consecutive patients with diarrhoea from whose stools campylobacter were isolated were investigated by sigmoidoscopy and rectal biopsy. Eight had definite proctitis, and in seven biopsy specimens were abnormal with histological changes ranging from non-specific colitis to gross colitis with goblet-cell depletion and crypt-abscess formation. Nine of the patients passed blood in their stools, and in all but one abdominal pain was a feature of the illness. Severe campylobacter colitis may be clinically, sigmoidoscopically, and histologically difficult to differentiate from ulcerative colitis and is a differential diagnosis in acute colitis.

Adolescent↗
PubMed1978

Value of bile-acid binding agents in post-vagotomy diarrhoea.

Cholecystectomy increases the incidence of post-vagotomy diarrhoea. The effect of agents which either bind bile acids or prevent their action on the colonic mucosa has been studied in 31 patients with post-vagotomy diarrhoea--15 had had vagotomy and pyloroplasty alone and 16 vagotomy and pyloroplasty and cholecystectomy. Cholestyramine was particularly useful after the combined operation. Aluminium hydroxide in large doses has a similar mechanism of action to cholestyramine and is cheaper and more palatable, but propranolol was of no value. This study suggests that the excretion and chemical composition of bile and the handling of bile acids by the small intestine is of fundamental importance in the pathogenesis of post-vagotomy diarrhoea.

Aluminum Hydroxide↗
PubMed1978

Should cholecystectomy be combined with vagotomy and pyloroplasty?

Duodenal ulcers and gallstones, two of the commonest surgical conditions, affect respectively 10% of men and up to 20% of the population. Although many detailed studies of the treatment of these conditions have been conducted, there is no report of the results of surgery when the conditions coexist. 60 patients who had undergone vagotomy, pyloroplasty, and cholecystectomy were compared with age and sex matched controls who had undergone vagotomy and pyloroplasty alone or cholecystectomy alone. In the early postoperative period after the combined procedure there was a very high incidence of post-vagotomy diarrhoea (48.3%, P equal to 0.00013) and bile-reflux gastritis. The findings implicate bile-acids--their excretion and handling by the small intestine--in the aetiology of post-vagotomy diarrhoea. Where the conditions coexist truncal vagotomy and pyloroplasty should be avoided in the treatment of the duodenal ulcer because of the risk of post-vagotomy diarrhoea and bile-reflux gastritis.

Adult↗