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Biomedical subjects

G M Lees

Publications and source records attributed to G M Lees.

At least 37 records · Page 2Linked to original sources
PubMed1991

Inflammatory pseudotumours of the lung: two cases and a review.

A discrete pulmonary mass lesion has different implications in children and in adults. Although infectious, congenital and metastatic etiologies are part of the differential diagnosis, inflammatory pseudotumour of the lung, or plasma cell granuloma, has emerged as the most common entity. The authors describe two patients with this poorly understood lesion and review the current state of knowledge. Both patients were young (4 and 5 years) and had recurrent lower respiratory tract infections; one patient was asthmatic. Both had persistent cough, and discrete lung lesions were apparent radiologically. Both children were treated by thoracotomy and excision of the tumour. There were no operative complications, and the convalescent period was uncomplicated. There were no signs of recurrence at follow-up 1 and 2 years postoperatively. This lesion is almost always benign, but aggressive behaviour has been documented. The authors recommend prompt conservative surgical excision.

Child, Preschool↗
PubMed1990

Monochorionic diamniotic minimally conjoined twins: a case report.

We present the second case of monochorionic diamniotic (MC/DA) conjoined twins. There was minimal conjunction, which was predominantly extrafetal and confined to the periumbilical ventral region. The omphalopagus twins, attached to a single forked umbilical cord, were connected by a shared umbilical hernia containing the ileum of twin B. The only visceral conjunction, located just within the belly of twin A, was midileal with the 2 separate ileums converging toward a short segment of shared muscularis propria and of side-to-side fistulization. Gastrointestinal and musculoskeletal anomalies were present in both twins with severe amyoplasia and arthrogryposis multiplex in twin A. Possible mechanisms underlying this unusual form of MZ twinning are discussed.

Abnormalities, Multiple↗
PubMed1990

The physiology of adaptation to small bowel resection in the pig: an integrated study of morphological and functional changes.

This study examined the adaptive response to extensive small intestinal resection in the juvenile domestic pig. Control animals underwent an ileal transection with end-to-end anastomosis, whereas resected pigs had a resection of the mid-75% of the total small bowel length. Animals were followed for 16 weeks. Resected animals gained less weight than controls, with no significant difference in feed intake per unit animal weight. In vivo fat, protein, carbohydrate, and total energy absorption were reduced in resected animals. Resected pigs had increased in vitro passive ileal uptake of fatty acids, cholesterol, and L-glucose, but no change in active D-glucose uptake. Microscopic morphology was altered, with an increase in the size of villi, a decrease in villous density, and no net change in mucosal surface area per unit of serosal surface area. Gross bowel length and diameter increased proportionately more in the resected than the control groups. This study demonstrated that massive resection results in a significant change in nutritional status in the growing pig. Functional and morphological changes occur, demonstrating intestinal adaptation. These findings suggest that this model would be suitable for the study of therapeutic modalities for the short-bowel syndrome in humans.

Animals↗
PubMed1988

An attempt to produce Ostertagia circumcincta infections in Mongolian gerbils.

Adult infections of Ostertagia circumcincta were successfully established in gerbils, although worm growth was retarded compared with infections in sheep. Chronic administration of beta-methasone to the host enhanced development of the parasite reproductive system but did not increase infection rate or prevent worm rejection. Infection rates achieved with single infections were not increased by using daily or weekly trickle infection regimes with or without prior exsheathment of larvae. Examination of stomachs from infected gerbils demonstrated pathological changes in the pyloric region which was the predilection site for O. circumcincta. This is in contrast to infections in sheep in which the fundic region of the abomasum is the preferred site.

Animals↗
PubMed1988

Dipetalonema viteae and Brugia pahangi transplant infections in gerbils for use in antifilarial screening.

Transplanted infections of Dipetalonema viteae and Brugia pahangi have been evaluated as tools for experimental chemotherapy. Attempts were made to establish these filariae in similar pharmacokinetic sites within the same host, so that direct comparisons of in vivo drug susceptibilities could be made. Unfortunately, it was not possible to establish B. pahangi in the subcutaneous tissues, the preferred site of D. viteae. Therefore, intraperitoneal B. pahangi and subcutaneously implanted D. viteae in gerbils were used for the study. D. viteae infections were significantly enhanced by concomitant infections with B. pahangi, while B. pahangi infection rates were unaffected by the presence of D. viteae. Experiments with amoscanate, CGP6140 and Mel W demonstrated the importance of employing both B. pahangi and D. viteae for antifilarial discovery work and the fundamental effect of parasite location on drug efficacy. D. viteae rapidly migrate from the peritoneal cavity of gerbils following implantation; twenty one hours after infection 73% of transplanted worms were found in the subcutaneous tissues. It was shown that the migration response could be used as a stringent parameter for demonstrating antifilarial activity. D. viteae were exposed to antifilarial drugs for 24 hours in vitro, washed and implanted into the peritoneal cavity of gerbils. At autopsy, 5 days later, 10(-8)M ivermectin and milbemycin D had prevented migration; CGP6140, amoscanate, suramin, flubendazole and furapyrimidone were also detected at less than 10(-6)M using this parameter. In all cases the migration response was more sensitive to drugs than parasite kill. Ivermectin's ability to inhibit worm migration through the tissues is discussed, with respect to the role of itinerant males in the reproductive cycle of Onchocerca volvulus.

Animals↗
PubMed1988

The potential of mice as animal models for antifilarial screening.

Transplanted infections of Brugia pahangi and Dipetalonema viteae in male BALB/c and CDI mice were investigated as models for evaluating potential antifilarial compounds. The physiology and genetics of the above mouse strains are better defined than any of the rodent species currently used for primary in vivo screening, facilitating a more reproducible means for predicting the filaricidal activity of compounds. The recoveries of B. pahangi macrofilariae, implanted intraperitoneally were greater than or equal to 50% up to six weeks after implant in both CDI and BALB/c mice. The recoveries of D. viteae macrofilariae, implanted subcutaneously, were greater than 50% up to four weeks post implant but had fallen to less than 30% by six weeks. The survival of B. pahangi and D. viteae macrofilariae simultaneously implanted into mice mimicked that seen with the mono-infections, but significantly better recoveries were obtained from dual implanted CDI mice compared to the BALB/c mice when the numbers of macrofilariae implanted were varied. Standard antifilarials were evaluated against D. viteae and B. pahangi dual implanted into either CDI mice or gerbils. The mouse dual implant detected significant worm reductions against D. viteae, B. pahangi or both with all antifilarials tested except CGP 6140. Similarly under the test conditions CGP 6140 was not detected in the gerbil assay, but there were marked differences in the results obtained with the mice and gerbil models. The reasons for these differences are discussed.

Animals↗
PubMed1986

Electrophysiology and morphology of vasoactive-intestinal-peptide-immunoreactive neurones of the guinea-pig ileum.

Simultaneous intracellular staining and electrophysiological recording techniques have been applied to neurones of guinea-pig myenteric plexus-longitudinal muscle preparations. With micro-electrodes filled with a solution of the fluorescent dye Lucifer Yellow, neurones were first characterized morphologically and electrophysiologically, and subsequently subjected to an indirect immunohistochemical method for the detection of vasoactive intestinal peptide (VIP)-like immunoreactivity. Cross-correlations of morphology, electrophysiology and VIP immunoreactivity were successfully achieved in a total of 164 neurones. Sixty-three had the slow after-hyperpolarization characteristic of AH neurones; 101 cells displayed fast excitatory post-synaptic potentials (e.p.s.p.s) in response to transmural or focal stimulation and were therefore, by definition, S neurones. Unequivocal VIP immunoreactivity was observed in 25 (25%) S neurones, which, with only one exception, had Dogiel Type I morphology (i.e. many short soma processes and a single long process). In contrast, AH neurones had Dogiel Type II morphology (i.e. smooth soma with several long processes) and none showed VIP immunoreactivity. In addition to cholinergic fast e.p.s.p.s., non-cholinergic slow synaptic inputs were evoked in seventeen of the twenty-two VIP-immunoreactive S neurones tested. Both the fast and slow e.p.s.p.s could be elicited by stimulation of the preparation, oral or aboral to the site of recording. These observations demonstrate that, in the guinea-pig ileum, myenteric plexus neurones showing VIP immunoreactivity are of a single electrophysiological type (S neurones) and belong to essentially one morphological class (Dogiel Type I).

Action Potentials↗
PubMed1986

A comparison of the response of Dipetalonema viteae and Brugia pahangi adult worms to antifilarial agents in vitro.

The drug response of Dipetalonema viteae and B. pahangi under various culture conditions have been evaluated. B. pahangi female worms proved to be more susceptible to CGP 6140 (4-nitro-4'-(N-methyl)piperazinyl thiocarbonylido-diphenylamine), CGP 20376 (N-(2-tert-butyl-5-methoxy-benzothiazol-6-yl)dithiocarbonic acid 5-(1-carboxyethyl)-ether) and amoscanate when glucose availability was restricted. This increased potency may be related to effects on glycogen metabolism by CGP 20376 and amoscanate. Using the parameters of parasite motility, survival, glucose consumption and microfilarial output, Eagles Minimum Essential Medium supplemented with 10% inactivated foetal calf serum plus either a 95% air:5% CO2 or a 95% N2:5% CO2 gas phase was shown to be highly suitable for short term maintenance (5 days). Examination of 12 drugs selected on their in vivo activity against B. pahangi and D. viteae demonstrated little difference between the drug susceptibilities of male and female worms. However, there were intrinsic differences between worm species. The relationship between these disparate susceptibilities and the reported in vivo efficacies of these drugs and the importance of selecting appropriate conditions for in vitro drug assays are discussed. Ivermectin at 10(-5) M caused a rapid flaccid paralysis and a complete suppression of microfilarial output by D. viteae. Despite continued paralysis of the worms they continued to utilise as much glucose as untreated worms over a 4 day period.

Animals↗
PubMed1985

The efficacy of benzimidazole anthelmintics against late fourth stage larvae of Trichostrongylus colubriformis in gerbils and Nippostrongylus brasiliensis in rats.

The efficacy of eight benzimidazole anthelmintics has been examined against Trichostrongylus colubriformis in gerbils and Nippostrongylus brasiliensis in rats, when the parasites were entering into the fourth and final moult. The dose--response slopes obtained from the data for both host--parasite systems did not deviate significantly from a non-parallel model, and were used for relative potency determinations. The T. colubriformis assay ranked the benzimidazoles in order of potency as follows: albendazole, oxfendazole, fenbendazole, cambendazole, mebendazole, oxibendazole, parbendazole and thiabendazole. This compares favourably with the expected relative efficacies against trichostrongyles in sheep. N. brasiliensis was found to be far less useful in this respect. All compounds tested, with the exception of thiabendazole, were highly effective against both parasites. The T. colubriformis/gerbil assay could be a very useful tool for preliminary in vivo evaluation and possibly in the early selective optimisation of chemical series.

Animals↗
PubMed1984

Slow intracellular potentials in AH-neurons of the myenteric plexus evoked by repetitive activation of synaptic inputs.

In after-hyperpolarization-neurons of guinea-pig myenteric plexus, several types of slow responses to repetitive activation of synaptic inputs were recorded. There were at least two types of slow excitatory depolarizing potential, both associated with an increased input resistance, but in one there was an abolition or marked attenuation of the amplitude of the slow after-hyperpolarization of the neuron, whereas in the other type the slow after-hyperpolarization was not significantly affected. Slow depolarizing and hyperpolarizing synaptic potentials associated with a decrease input resistance were also recorded in some neurons following transmural stimulation. The neural processes responsible for these slow potentials in after-hyperpolarization-neurons showed no preferential projection within the myenteric plexus.

Animals↗
PubMed1984

A summary of preoperative and postoperative cardiorespiratory performance in patients undergoing pectus excavatum and carinatum repair.

Preoperative and postoperative pulmonary function tests and progressive work exercise performances were compared for fourteen pectus excavatum and five pectus carinatum patients who underwent operative repair. No changes could be documented in the pectus carinatum patients. The excavatum patients demonstrated a small improvement in total lung capacity (P less than .02) and a significant improvement in maximal voluntary ventilation (P less than .001). In addition, the exercise performances were improved for the excavatum patients postoperatively as quantitated both by the total exercise time and the maximal oxygen consumption (P less than .01). In addition, at any given work rate, the excavatum patient demonstrated a lower heart rate and higher minute ventilation after operation. These findings support the hypothesis that both the restricted cardiac stroke volume and the increased work of breathing that have been described in pectus excavatum patients can be ameliorated by operative intervention.

Adolescent↗
PubMed1984

Electrophysiology and enkephalin immunoreactivity of identified myenteric plexus neurones of guinea-pig small intestine.

Intracellular injection of the fluorescent dye, Lucifer Yellow CH, revealed the shapes of neurones in the myenteric plexus of the guinea-pig ileum, and these shapes were correlated with the electrophysiological properties and enkephalin immunoreactivity of the neurones. A total of eighty-three neurones were filled using electrodes containing a 5% solution of the dye. Forty-six cells had many short processes and a single long process (Dogiel type 1) and twenty-four cells had essentially smooth somas and one to eight long processes (Dogiel type II). Thirteen cells could not be put into either group. Enkephalin-like immunoreactivity was detected in twenty-two of the forty-six Dogiel type I cells. Eighteen of these had club-like short processes. No other cells of the eighty-three showed enkephalin-like immunoreactivity. Electrodes filled with a 0.5% solution of Lucifer Yellow in 0.5 M-KCl were used to record from and simultaneously to inject dye into 240 neurones. Eighty-six nerve cells had a slow after-hyperpolarization following the action potential (AH cells) and forty-six nerve cells had no after-hyperpolarization but exhibited a fast excitatory synaptic potential (S cells). The other cells could not be unequivocally identified by their observed electrophysiological characteristics. Almost all S cells (forty-two of forty-six) were Dogiel type I, while eighty-two of the eighty-six AH cells were Dogiel type II. Fifty S cells (eight located geometrically, forty-two by dye injection) and ninety-one AH cells (twenty-six located geometrically, sixty-five by dye injection) were examined for enkephalin immunoreactivity. Fifteen of the S cells were reactive, whereas all of the AH cells were unreactive. It appears that prolonged impalements reduce immunoreactivity so that the proportion of reactive neurones in this series is an underestimate of the true proportion of S cells with enkephalin-like immunoreactivity. The results suggest that a substantial proportion of the S cells in myenteric ganglia contain enkephalin immunoreactivity while none of the AH cells do. The enkephalin neurones have a distinctive shape and are all Dogiel type I cells. AH cells are nearly always Dogiel type II.

Action Potentials↗
PubMed1983

Fluorescence-microscopic measurement of intracellular cytochrome P-450 enzyme activity (ethoxyresorufin O-de-ethylation) in unfixed liver section.

A fluorescence-microscopic method has been developed for measurement of the intracellular kinetics of the cytochrome P-450 reaction, ethoxyresorufin O-de-ethylation, in individual hepatocytes in unfixed non-frozen liver sections obtained from control or 3-methylcholanthrene-pretreated mice. De-ethylation was enhanced in the presence of salicylamide, but inhibited in the presence of alpha-naphthoflavone, A total of 21 reaction rate curves (fluorescence of the metabolite, resorufin, versus time) were constructed for different individual hepatocytes and groups of two or three hepatocytes, in a total of 12 sections from four control and eight 3-methylcholanthrene-induced mice. No two reaction curves were identical, but the curves were classified, by similarity of curve shape and fluorescence intensity, into three control categories and four 3-methylcholanthrene-induced categories. It was considered that the data represented a total of seven types of hepatocytes, which differed in their ethoxyresorufin de-ethylase reaction characteristics. Hepatocytes in the sections from 3-methylcholanthrene-pretreated mice showed higher de-ethylase activities than the hepatocytes from control mice, but the increase in activity covered a wide range of values, from 3-fold to 17-fold higher than the mean control value, suggesting that 3-methylcholanthrene did not induce ethoxyresorufin de-ethylation to the same extent in all hepatocytes.

Animals↗
PubMed1983

Morphological studies of electrophysiologically-identified myenteric plexus neurons of the guinea-pig ileum.

The morphology of neurons in the myenteric plexus of the guinea-pig ileum has been studied by means of the intracellular application of Procion Yellow. Sixty-six electrophysiologically-unidentified cells showed a great variety of soma shapes and number of processes, the vast majority of the longer of which were circumferentially-orientated. The electrophysiological properties of an additional 47 neurons were ascertained; 29 were neurons with a slow after-hyperpolarization (AH-neurons), 14 showed fast excitatory synaptic potentials (S-neurons) and 4 were of neither category. Twenty-two of the AH-neurons had a smooth soma outline and, on average, each had 5 processes, of which the great majority of long processes were circumferentially-orientated and intraganglionic. The projection ratios of oral:circumferential:aboral processes were 6:61:9. Branching was a prominent feature of the processes. In contrast, a large soma with many broad, short processes was a feature of 8 of 14 S-neurons studied. The average number of processes was 8.6 per cell and relatively more of them were aborally-directed, giving projection ratios of 2:21:7. There was, however, such a variation and overlap in the morphology of AH- and S-neurons that it was not possible to achieve a simple, reliable classification. It is concluded that many neuronal processes may be intraganglionic and that longitudinal ones are mainly aboral. From the varied morphological characteristics of AH-neurons, it is unlikely that these neurons subserve a single function in the plexus. For the same reasons S-neurons may fulfil different physiological roles.

Animals↗
PubMed1983

Improvement of in vitro culture conditions of Brugia pahangi four day old developing larvae for use in an antifilarial drug assay.

Four day old third stage larvae of Brugia pahangi were cultured in the presence of differing concentrations of early passage dog kidney cells and inactivated foetal calf serum. After a six day culture period worm length, number of moults and worm mortality were determined. Analysis of the length data demonstrated a significant interactive relationship between cell and serum concentration. The greatest increases in length were obtained using an initial cell density of dog kidney cells of 40 x 10(4) plus a serum concentration of 10%. (The surface area of all culture vessels was 2.0 cm2). In addition moulting occurred earlier and was more prolific with higher cell and serum concentrations. The response of larvae to antiparasitic agents in the presence or absence of a confluent dog kidney feeder layer was then compared to determine whether the inclusion of cells altered drug effects. From this it was found that the killing effects of flubendazole, albendazole, furazolidone, levamisole and nifurtimox at their minimum effective concentrations were delayed under biphasic culture conditions. It is suggested that this is an advantage and will improve the selectivity of the assay over and above an assay which does not include a cell feeder layer. In addition the improved growth rates obtained in cultures containing dog kidney cells should mean an increase in test sensitivity to agents capable of disrupting biosynthesis.

Aging↗
PubMed1981

Antibiotic-associated colitis: an in vitro investigation of the effects of antibiotics on intestinal motility.

1 Nine antibiotic compounds in common use were studied to determine their ability to affect intestinal motility in vitro, in the guinea-pig ileum and rabbit colon. 2 Ampicillin, doxycycline, mecillinam and metronidazole were without effect over a concentration range which included typical serum levels found when these drugs are used therapeutically. 3 Clindamycin, gentamicin, kanamycin, pivmecillinam and trimethoprim were all found to inhibit evoked and reflex responses of the guinea-pig ileum but only clindamycin and trimethoprim also affected evoked responses of the rabbit colon. 4 Kanamycin and gentamicin appeared to have a predominantly pre-junctional action, pivmecillinam and trimethoprim a predominantly post-junctional action. Clindamycin had a pre-junctional action at low concentrations and long exposure times, and a post-junctional action at high concentrations and short exposure times. 5 The concentration of each antibiotic required to inhibit the peristaltic reflex of the guinea-pig ileum was less than that required to inhibit its responses to electrical stimulation or exogenous acetylcholine or histamine but greater than the serum levels associated with their respective use in therapeutic doses. 6 A sequence of events whereby antibiotic-induced alterations in gastro-intestinal motility could lead to the development of pseudomembranous colitis is proposed.

Acetylcholine↗