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Biomedical subjects

L Hartley

Publications and source records attributed to L Hartley.

At least 55 records · Page 3Linked to original sources

Post-choledochoenterostomy 'sump syndrome'.

The 'sump syndrome' is an uncommon, late complication of a side-to-side choledochoenterostomy. Five patients with this syndrome were encountered over a 5-year period. Pain or cholangitis was the clinical presentation in four patients, whereas one patient presented with secondary septic arthritis and a hepatic abscess. Liver function tests were mildly abnormal in each patient. All patients had a stomal size of less than 1 cm as assessed by forward- or side-viewing endoscopy. Endoscopic retrograde cholangiography revealed either stones or debris in the distal common bile ducts of all patients. Four patients had a surgical clearance of their duct with concurrent closure of the choledochoduodenostomy in three patients and the creation of a Rouxen-Y end-to-side choledochojejunostomy in the fourth patient. The other patient had an endoscopic sphincterotomy performed. After 1-4 years of follow-up, four patients have had a total resolution of symptoms. The other patient with follow-up for 4 years has had one episode of cholangitis which resolved rapidly with antibiotic treatment. The pathogenesis and clinical spectrum of the sump syndrome are reviewed and current management strategies are discussed.

Abdominal Pain↗

Hierarchy of cytotoxic T cell clones. I. Reversal of resistance to lysis and killing between anti-hapten cytotoxic T cells.

Cells from clones of anti-hapten cytotoxic T lymphocytes (CTL) can act as both effector cells and, when treated with the specific hapten, as target cells. Individual clones can kill haptenated cells only from other clones that are less efficient killers. Clones specific for both fluorescein and trinitrophenol could be ordered in a single hierarchy in which resistance to lysis correlated with lytic efficiency. When the killing efficiency was reduced with phorbol myristate acetate (PMA) or the colchicine analogue, Colcemid, the degree of resistance to lysis was also reduced. The use of PMA-treated fluoresceinated targets greatly enhanced intraclonal killing and similarly lead to a repositioning of clones within the hierarchy of normal cells. By the haptenation of appropriate clones, efficient CTL could kill cells from other clones in a direction apparently opposite to recognition. The results demonstrate that effects other than antigen recognition of the target cell may result in variations in the nature of T cell immune responses.

Animals↗

Hierarchy of cytotoxic T cell clones. II. Intraclonal triggering of lysis by hapten-specific CTL.

Cells from clones of anti-hapten murine cytotoxic T lymphocytes (CTL) can act as both target and effector cells, but will not lyse members of the same clone. The effect of haptenation on the cytolytic activity of anti-fluorescein (FL) and anti-trinitrophenol (TNP) CTL clones was examined. Treatment of anti-FL clones with fluorescein isothiocyanate or anti-TNP clones with trinitrobenzene sulphonic acid induces these clones to kill in an antigen-independent fashion. Targets killed by the haptenated CTL included syngeneic and allogeneic B lymphocyte blast cells, P815, YAC-1 and in one case human GM 4072 tumor cells. The importance of CD8 and T cell receptor (TCR) occupancy is demonstrated by the ability to block autotriggering by antibody directed against Ly 2 and the TCR. The results demonstrate that effects other than antigen recognition of the target play a role in the final outcome of effector-target cell interactions and provide a mechanism which could lead to autodestruction and immunosuppression particularly in some types of viral infection.

Animals↗

Hypertrophy of radial and ulnar arteries following denervation of the chicken wing.

Denervation of radial and ulnar arteries in the growing and adult domestic fowl was achieved by unilateral sectioning of the brachial plexus. Eight weeks later the denervated arteries and those of the contralateral wing were examined with light- and electron microscopy to determine the effect of denervation on arterial structure. In growing fowls, the area of the media in radial and ulnar arteries was increased by 29% and 25%, respectively, after denervation. The number of smooth muscle layers was also significantly increased by 16% (radial) and 14% (ulnar), but no significant variation was seen in the wall/lumen ratio of either growing artery. In adult fowls, the area of the media was increased by 93% (radial) and 32% (ulnar) following denervation and the number of smooth muscle cell layers increased by 39% (radial) and 11% (ulnar). There was also an increased wall/lumen ratio of 64% (radial) and 92% (ulnar). These results indicate that hyperplasia of smooth muscle has occurred in response to denervation. Flow-cytometric DNA analysis of growing arteries also indicates that the increase in muscle-cell volume is a result of cell division (not polyploidy) since no significant differences were found between the control and denervated arteries in any stages of the cell cycle.

Animals↗

Differentiated thyroid carcinoma, intermediate type.

A thyroid carcinoma showing histological and histochemical features of both follicular and parafollicular cell carcinoma was diagnosed in a 56 year old male. Previously the two cell types have been considered to be derived from embryologically distinct and separate precursors. The unusual combination of the two cell types in this tumour suggests the possibility that the cell lines may be derived from a common stem cell with the potential of differentiating into both follicular and parafollicular cells. The tumour was aggressively invasive and had metastasized widely to lymph nodes at the time of presentation. It represents an example of the recently described entity of differentiated thyroid carcinoma of intermediate type.

Adenocarcinoma↗

Hyperactivity, drugs and attention to features in a story.

Twenty hyperactive children were divided into two groups of 10 volunteers. Group 1 was taken off its medication (methylphenidate) for two weeks and group 2 was kept on its medication at the usual dosage. About one week following the cessation of medication subjects from both groups heard a story and were shown some pictures illustrating events in the story. They were then tested on their memory for this material. One week later their delayed retention was tested. Both immediate and delayed retention was better in those children who remained on medication. This was especially true for the incidental material.

Attention↗

Early gastric cancer.

Thirty patients with early gastric cancer were studied as part of a consecutive series of 308 gastric cancers, giving a proportion of 9.7%. Twenty-eight of the early gastric cancer patients were symptomatic, pain being the most common symptom. Endoscopy proved more effective than barium studies as a first investigation but the diagnosis rate at first examination was still only 69%. Seven patients with early gastric cancer had lymph node spread at the time of presentation. Five patients eventually died of cancer metastases. There was a high incidence of benign peptic ulceration (50%) and this with lymph node metastasis was an unfavourable prognostic feature. Only four of the 26 patients submitted to standard surgical resections died of cancer. This study supports the concept that early gastric cancer does indeed occur in Western man and the five year survival rate (65%) is much higher than for late gastric cancer (13%). The high incidence of metastasis at the time of presentation may account for the difference between our survival rate for early gastric cancer, and that reported from Japan.

Adenocarcinoma↗

Difficulties in the endoscopic diagnosis of gastric and oesophageal cancer.

A study was made of 116 patients with gastric or oesophageal cancer, in whom endoscopy was negative, or biopsy was negative or not performed. The most common problems were the presence of pyloric or oesophageal stricture (sometimes with excessive luminal content) and difficulty in obtaining diagnostic biopsy material in linitis plastica, early gastric cancer, lymphoma and sarcoma. Problems also occurred from failure to biopsy apparently benign conditions and from delay in a second endoscopy. Some cancers were regarded as benign ulcers and treated as such by drugs or surgery because more reliance was placed on endoscopic biopsy than on the endoscopist's opinion of the macroscopic appearance. In 17 of the 16 patients there was delay, incorrect management or further difficulty in diagnosis.

Diagnostic Errors↗

Morbidity and mortality of operative intubation for malignant oesophageal obstruction.

In 33 patients who underwent operative intubation of carcinoma of the oesophagus or gastric cardia, there were nine postoperative deaths (mortality 27%). Only 15 patients (46%) had no further operative procedure or anaesthetics, but their mean survival was only 3.7 months. Nine patients (27%) required a total of 17 procedures after the placement of their original tube. Operative intubation has a similar mortality to resection but the survival times are short. Whenever possible palliative resection or endoscopic intubation is to be recommended.

Aged↗

Phaeochromocytoma in Queensland--1970-83.

A statewide survey was conducted in Queensland to record all cases of phaeochromocytoma between the years of 1970 and 1983 inclusive. There were 46 cases giving an incidence of 1.55/million population per year. Twenty-nine patients (63%) were successfully treated while 10 patients (22%) died of the tumour effects. Seven cases (15%) were found incidentally at autopsy, though at least one showed diagnostic clinical features before death. Five patients (11%) had extra adrenal phaeochromocytoma, five patients (11%) had multiple tumours, four patients (9%) had multiple endocrine neoplasia and three patients (7%) had clinically malignant tumours. Of 13 patients suffering a major adrenergic crisis only six survived. Five patients with unsuspected phaeochromocytoma suffered crisis under anaesthesia and only one survived. Only one of the patients dying of benign phaeochromocytoma had adequate ante mortem adrenergic blockade. Of all patients in the series 35% were not diagnosed in life.

Adolescent↗

Selective inhibition by NPT 15392 of lymphocyte cyclic GMP phosphodiesterase.

Cyclic nucleotide phosphodiesterases were measured in mouse spleen and thymus lymphocyte membranes and soluble fractions and in extracts of canine tracheal smooth muscle. The immunostimulant erythro-9(2-hydroxy,3-nonyl) hypoxanthine (NPT 15392) was found to be a potent and relatively selective inhibitor of mouse lymphocyte cyclic GMP phosphodiesterase, with IC50 values 15-180 times greater for cyclic AMP than cyclic GMP phosphodiesterases. The greatest inhibition by NPT 15392 was found using 10 microM substrate, and inhibition was greater in membrane than soluble forms of phosphodiesterase. Spleen soluble enzymes were separated by DEAE Bio-Gel A column into six peaks. A major form of cyclic GMP phosphodiesterase was inhibited effectively by NPT 15392 in a competitive manner (Ki = 50 microM). Cyclic AMP phosphodiesterase activity in the same fraction, but representing only a fifth of the total activity, was also inhibited (Ki = 70 microM). Other soluble enzymes were not affected significantly. Membrane bound enzymes were solubilized and separated into three peaks. One with high affinity for cyclic GMP was strongly inhibited (Ki = 10 microM) by NPT 15392. Inosine and isoprinosine were one-tenth to one-hundredth as effective as NPT 15392 as cyclic nucleotide phosphodiesterase inhibitors. Incubation of mouse splenic lymphocytes with NPT 15392 for 48 hr resulted in enzymes with altered responsiveness to the drug in broken cell assays: inhibition of cyclic GMP hydrolysis was enhanced while that of cyclic AMP hydrolysis was decreased. Among three separated and characterized forms of tracheal smooth muscle phosphodiesterase, NPT 15392 inhibited the low Km cyclic GMP phosphodiesterase 6-10 times more effectively than the other enzymes. These data suggest that the immunopharmacologic activities of NPT 15392 may include specific cyclic GMP phosphodiesterase inhibition as one of several possible mechanisms.

3',5'-Cyclic-AMP Phosphodiesterases↗

Hyperactivity, drugs and attention deficit.

Thirty-two hyperactive children who were under imipramine or methylphenidate medication took part in the experiment. The children were asked to learn a set of paired associate pictures containing a salient, central, figure and a secondary figure below. Free recall of all pictures was scored both immediately and seven days later. The children were subdivided into four groups according to the classical state-dependent learning paradigm. Group 1 was withdrawn from medication on both trials, groups 2 and 3 were withdrawn from medication on the first or second trial and group 4 received medication on both trials. No drug effects were found in immediate total recall. Delayed free recall was improved when original learning was under the drug state. This result was related to the proposal that arousing words are better remembered in delayed recall. Delayed recall of the secondary stimuli was particularly improved by the drugs during learning. Drug state dependency of the children's memory was also shown.

Adolescent↗

Toxic adenoma in childhood--case report.

A 12-year-old girl was noted to have a left sided thyroid nodule on routine examination. Although clinically euthyroid she was found to have an elevated T3 value, and the TSH failed to rise following TRH injection. Thyroid scan showed a hyperfunctioning nodule in the left lobe of the thyroid gland. Following surgical removal of the nodule the patient became biochemically euthyroid and a repeat thyroid scan demonstrated the previously suppressed normal right lobe.

Adenoma↗