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Biomedical subjects

J D Harrison

Publications and source records attributed to J D Harrison.

At least 19 recordsLinked to original sources
PubMed1992

Recombinant tissue-type plasminogen activator is superior to streptokinase for local intra-arterial thrombolysis.

The results of local intra-arterial thrombolysis in 98 patients treated with streptokinase and 69 patients treated with recombinant tissue plasminogen activator (rtPA) have been compared. The two groups of patients were well matched and their treatment protocols were identical except with regard to the thrombolytic agent used. Strict criteria for defining successful thrombolysis were used. Successful lysis was achieved in 40 of 98 patients (41 per cent) receiving streptokinase and 40 of 69 patients (58 per cent) receiving rtPA (P less than 0.05). The time to lysis was significantly shorter with rtPA, median time 22 h, than with streptokinase, median time 40 h (P less than 0.002). There was no difference in the incidence of haemorrhagic complications. These results suggest that rtPA is superior to streptokinase for local intra-arterial thrombolysis.

Adult↗
PubMed1992

Increase of microliths in inactive salivary glands of cat.

Secretory inactivity could be a factor in the formation of microliths, and so their occurrence in feline salivary glands after the secretory inactivity produced by parasympathectomy was investigated. Parasympathectomy was followed by a greatly increased occurrence of microliths in the submandibular salivary gland, but not in the parotid and sublingual, which may relate to residual secretory activity in these glands. This discovery suggests that secretory inactivity may indeed be a factor in the production of microliths in human salivary glands, and consequently of chronic sialadenitis and sialothiasis.

Animals↗
PubMed1992

Production of microliths and sialadenitis in rats by a short combined course of isoprenaline and calcium gluconate.

The relationship between microliths and sialadenitis in man is unclear, so an attempt was made to investigate it experimentally in rats with the use of isoprenaline and calcium gluconate either alone or combined. The acini of the submandibular and parotid glands of rats that were given isoprenaline were enlarged, and degenerate acinar cells were seen, with extravasated secretions in the submandibular gland. Similar changes were seen in the submandibular and parotid glands of rats that were given isoprenaline combined with calcium gluconate; in addition, ductal microliths with regions of atrophic sialadenitis were observed. The results suggest that there is temporary obstruction to the salivary flow after isoprenaline is injected, and in the rats that were also given calcium gluconate some of the stagnant saliva calcified to form microliths, which produced a lasting obstruction and obstructive sialadenitis. This supports the possibility that microliths, which are present in normal salivary glands of man, are a primary etiologic factor in sialadenitis.

Animals↗
PubMed1992

Estimates of embryonic and fetal doses from 239Pu.

Previously reported studies on the transfer of 238Pu from the maternal circulation to the developing embryo and fetus in rats and guinea pigs have provided data for developing dosimetric models. The highest concentrations of 238Pu were measured in the yolk sac. In late gestation, preferential uptake of 238Pu in liver and bone was observed. The data obtained, together with other published information, have been used to estimate in utero doses to hemopoietic tissues, taking account of transfer to the blastocyst/egg cylinder, yolk sac, liver, and bone marrow. From animal data, the concentration ratios relative to maternal liver for these tissues were taken to be 0.1, 2, 0.01, and 0.02, respectively, and were applied to periods of human gestation of 0-2.5 wk, 2.5-6 wk, 6-12 wk, and 12-38 wk, respectively. Doses to fetal tissues from 239Pu were calculated for chronic ingestion by the mother for a total of 1.8 kBq 239Pu during the year of pregnancy, giving a committed effective dose to the mother of 1 mSv. On this basis, the total in utero dose to hemopoietic tissue was about 2 microSv compared with red bone marrow doses of 34 microSv to the mother for the year. The yolk sac and bone marrow dominated in utero doses. The total dose to hemopoietic tissue in the offspring to age 70 y, taking into account the activity present at birth and including in utero doses, was estimated as 24 microSv compared with a maternal dose to red bone marrow of 2.5 mSv. An acute maternal intake of 1.8 kBq by ingestion during the period of yolk sac hemopoiesis would result in the highest in utero dose, estimated at about 36 microSv. However, activity at birth would be lower, giving only a small additional dose.

Animals↗
PubMed1991

Oestrogen receptor D5 antibody is an independent negative prognostic factor in gastric cancer.

Recent studies have demonstrated oestrogen receptors in tissues other than those considered to be sex hormone responsive, for instance in gastric cancer. In vitro experiments have shown oestradiol to be trophic to gastric cancer cell lines. The effect of D5 (an oestrogen receptor-related protein) status on survival was therefore studied in a group of 188 consecutive patients undergoing surgery for gastric cancer. Ninety-two patients (49 per cent) were positive for the D5 antibody. There were no differences between the D5-positive and D5-negative groups for age or adverse prognostic features such as high grade tumours or advanced stage. The D5-negative patients had a significant survival advantage over the D5-positive patients. The 95 per cent confidence interval for survival in the patients with D5-negative tumours was 63-101 weeks compared with 39-66 weeks for the patients with D5-positive tumours (Mantel-Cox statistic = 4.15, P = 0.042). Prognostic factor analysis with a Cox proportional hazards model showed tumour stage (P = 0.001) and D5 status (P = 0.003) to be significant independent factors in gastric cancer. Laurén type, grade and gender were not significant independent factors in this small series.

Aged↗
PubMed1991

Mucosubstance histochemistry of pleomorphic adenoma of parotid and submandibular salivary glands of man: light and electron microscopy.

Lumina and adluminal cells in human salivary gland pleomorphic adenomas were found to contain neutral, carboxylated, and occasionally sulphated glycoproteins. A variable component of luminal contents and secretory granules did not appear to contain glycoprotein and possibly consisted of protein. Glycosaminoglycans, which appeared to be hyaluronic acid and chondroitin sulphate, were demonstrated rarely in lumina, often between epithelial cells, and forming the matrix of myxoid tissue and, together with collagen, chondroid tissue. No differences were seen between tumours from parotid glands and those from submandibular glands. Glycoproteins demonstrated in the epithelium are similar to those of intercalary ducts of parotid and submandibular glands, and may represent a primitive form of salivary secretion. Glycosaminoglycans secreted intercellularly by epithelial cells cause their increasing separation to form myxoid or chondroid tissue. This stromalization extends to lumina to produce a loss of epithelium. Pleomorphic adenoma appears to be a manifest example of variable derepression of the genotype.

Adenoma↗
PubMed1991

Azithromycin levels in plasma and gastric tissue, juice and mucus.

Azithromycin is the first member of a new class called the azalides. Its distribution in gastric tissues was studied in 27 patients (mean age 66 years) with proven gastric cancer due to be resected. Five groups of patients received a single 500 mg oral dose of azithromycin 24, 48, 72, 96 or 120 h pre-operatively. Samples of blood, gastric juice, mucus and gastric tissue were taken and azithromycin assayed by high performance liquid chromatography. There was an increase in the level of azithromycin in gastric juice up to the 73-96 h period reaching a median peak of 0.20 micrograms/ml. There were higher levels of azithromycin in gastric mucus (approximately double the maximum attained in gastric juice) at each of the time periods to 120 h after the dose of azithromycin. Much higher levels were seen in the gastric tissue (median peak of 4.6 micrograms/g), which were statistically significant compared with gastric juice for the first two time periods (24-48 h, p = 0.005; 49-72 h, p = 0.012). Concentrations seen in the gastric tissue specimens were between five- and 10-fold greater than those seen in gastric mucus, and approximately 20-fold greater than the levels seen in gastric juice at each of the time periods after dosing. It is concluded that remarkably high levels of azithromycin are found in gastric tissue within 24 h of a 500 mg oral dose and that these levels persist over a five-day period. There exists a significant concentration gradient from gastric tissue to gastric juice. Such levels may be advantageous in the therapy of Helicobacter pylori infections.

Administration, Oral↗
PubMed1991

The gastrointestinal absorption of the actinide elements.

The greatest uncertainty in dose estimates for the ingestion of long-lived, alpha-emitting isotopes of the actinide elements is in the values used for their fractional absorption from the gastrointestinal tract (f1 values). Recent years have seen a large increase in the available data on actinide absorption. Human data are reviewed here, together with animal data, to illustrate the effect on absorption of chemical form, incorporation into food materials, fasting and other dietary factors, and age at ingestion. The f1 values recommended by the International Commission on Radiological Protection, by an Expert Group of the Nuclear Energy Agency and by the National Radiological Protection Board are discussed.

Actinoid Series Elements↗
PubMed1991

The incorporation of plutonium by the embryo and fetus of rats and guinea-pigs.

The transfer of 238Pu from the maternal circulation to the developing embryo and fetus was studied in rats and guinea-pigs to provide data for the development of dosimetric models for the human embryo and fetus. Following administration at different stages of gestation, measurements were made after 3 days in the rat and 7 days in guinea-pigs. The amount transferred was greater after administration at later stages of gestation, up to a maximum of about 0.8-0.9% of the injected activity per fetoplacental unit (FPU) and about 0.2% per fetus in both species. In advanced gestation the yolk sac, the initial site of haemopoietic stem cells, contained up to 80% of the total activity in the FPU in rats, compared with about 25% for the guinea-pig; retention in placental trophoblast was greater in the guinea-pig. The concentrations of 238Pu in the yolk sac were generally about two to three orders of magnitude greater than fetal concentrations and of the same order as in maternal liver and bone. In both species, concentrations in the embryo and fetus were greatest after injection early in gestation, reached their lowest around mid-organogenesis and increased again in later gestation. The fetus:mother whole-body concentration ratios in late gestation were about 0.1 and 0.05 in rats and guinea-pigs, respectively. Measurements were also made of the 238Pu retention in neonates at birth. In guinea-pigs the liver accounted for about 6-9% of retained activity; similar values for femora indicated skeletal retention of about 60-80%. For administration at each stage of gestation, and particularly at early stages, transfer of 238Pu to the fetus continued throughout gestation but concentrations decreased due to fetal growth.

Animals↗
PubMed1991

Gastrointestinal absorption of neptunium and curium in humans.

The gastrointestinal absorption of Np and Cm has been determined in five male adult volunteers. The Np and Cm, which were in citrate solution, were taken with food. An initial experiment with each individual determined the fraction of each element excreted in the urine following intravenous administration. Subsequently, the results for urinary excretion for the two routes of administration were used to calculate the fractional absorption (f1) of ingested Np and Cm. The mean f1 values were: Np (2.0 +/- 0.2) X 10(-4), range (1.2-2.9) X 10(-4), and Cm (1.7 +/- 0.3) X 10(-4), range (0.95-3.0) X 10(-4), the quoted uncertainties being the standard error of the means. Currently, the International Commission on Radiological Protection recommends a value of 10(-3) for both elements. Cumulative urinary excretion over 1 wk after intravenous injection accounted for about 20%-40% of administered Np and 7%-10% of Cm. At the conclusion of the experiment, the total committed effective dose equivalent for each volunteer was calculated to be in the range 130-250 microSv, based on the individual f1 values, and, in some cases, a knowledge of the rate of clearance of 239Np through the gut as measured by whole-body counting.

Adult↗
PubMed1991

Does bipolar electrocoagulation time affect vessel weld strength?

The value of the bipolar electrocoagulator in the haemostasis of bleeding ulcers is controversial. We have therefore investigated the effect of different coagulation times on vessel weld strength achieved by the bipolar device. Welds were then made in vessels of known diameter using a standard 10F endoscopic haemostatic probe at coagulation times of two and 20 seconds. The intravascular temperature achieved at each time was measured. Vessel weld strength achieved by bipolar electrocoagulation was much greater at 20 seconds (approximately twice that at two seconds) and was highly significantly greater at all vessel diameters. There was a gradual reduction in weld strength with increasing vessel diameter, an effect that was seen for both two and 20 seconds of electrocoagulation. Intravascular temperature was significantly higher at 20 seconds than at two seconds. We conclude that vessel weld strength is related to coagulation time and that any future studies comparing the bipolar electrocoagulator with other haemostatic devices should use longer periods of bipolar electrocoagulation and record the coagulation time in order to optimise the clinical value of the device.

Animals↗
PubMed1991

Measurement of testicular blood flow at orchiopexy with a solid state laser.

We have evaluated the solid state laser as a means of determining testicular blood flow at operation. A solid state laser was used to measure blood flow before mobilization of cryptorchid testes, and subsequently after mobilization and placement within a subcutaneous scrotal pouch. Testicular volume was calculated. The median blood flow (ml/100 gm/min) before mobilization was 8.96 (range, 3.43 to 27.2). After mobilization a modest rise to 9.39 (range, 1.82 to 23.75) occurred, which was not statistically significant. However, heterogeneity existed in the response; 11 testes showed a median fall of 8.07 (range, 1.59 to 15.36), which was significant compared to the initial value; 16 testes showed a variable degree of hyperemia with a rise of 2.57 (range, 0.1 to 12.7), which was also significant compared to the initial value; two testes showed no change. The testes that showed a fall in blood flow were all high abdominal testes, which required the most mobilization. The mean testicular volume was 0.38 cc (SEM, 0.03 cc). No difference was noted in size between testes with a net rise in blood flow (mean volume, 0.38 cc) and testes with a net fall in blood flow (mean volume, 0.375 cc). No relationship was noted between testicular size and blood flow. We conclude that the solid state laser is a simple means of measuring testicular blood flow at orchiopexy and may provide a method of deciding which testes should undergo microvascular replantation on the basis of inadequate perfusion per-operatively.

Cryptorchidism↗
PubMed1991

Primary B-cell immunoblastic lymphoma of pancreas.

Extranodal lymphoma may present as an abdominal mass without evidence of disease elsewhere. Predominant pancreatic involvement with lymphoma is rare. Presenting as a pancreatic mass, it may be difficult to differentiate if from carcinoma. Ultrasound-guided fine needle biopsy and immunocytochemistry are helpful in establishing a histological diagnosis. It is important to differentiate lymphoma from carcinoma, because lymphoma is treated differently and has a better prognosis.

Adult↗
PubMed1990

The effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma.

Gastric cancer remains a disease with a very poor prognosis, and there is no safe and effective form of therapy for advanced disease. Evidence is now abundant to show that gastrin stimulates the growth of both gastric and colorectal cancer cells in vitro and in vivo, and that blockade of gastrin receptors can prolong survival in xenografted nude mice. We have thus performed a randomized, controlled study of the gastrin/cholecystokinin receptor antagonist proglumide as therapy in 110 patients with gastric carcinoma. Proglumide had no overall effect on survival (Mantel-Cox statistic = 0.5, P = 0.48). The 95% confidence interval for the proglumide treated group was 260 to 474 days compared to 230 to 372 days for the control group. No significant difference was seen with proglumide, which has a relatively low affinity with the gastrin receptor and also has partial agonist activity. Drugs that are far more specific and potent gastrin receptor antagonists are becoming available, which may have a greater effect on survival, and further clinical trials of such compounds are clearly indicated to determine the efficacy of hormonal control of gastrointestinal malignancy.

Aged↗
PubMed1990

The gastrointestinal absorption and retention of niobium in adult and newborn guinea pigs.

The gastrointestinal absorption of 95Nb ingested in milk by adult guinea pigs on a milk-supplemented diet was estimated as 0.8 +/- 0.2% (SEM; n = 4) and a value of 1.4 +/- 0.2% was obtained for guinea pigs fasted for 24 h before and 2 h after the oral administration of 95Nb in a citrate solution. The absorption in 2-day-old animals given the 95Nb-citrate solution was estimated as 1.5 +/- 0.2% (SEM; n = 3). These results support the values currently used for radiological protection purposes to calculate doses from the ingestion of niobium isotopes; these are 1% for adults and 2% for infants in the first year of life. Intestinal retention of niobium in newborn guinea pigs was low, unlike retention in other species, but consistent with observations of the retention of other elements in guinea pigs. It is considered that retention in human neonates is likely to be most similar to that in guinea pigs. Whole-body retention of 95Nb after systemic administration in citrate solution was slightly lower in 2-day-old guinea pigs than in adults, with rapid excretion of about 50% over the first day compared with 40% in adults. Subsequent clearance was similar in the two age groups with a retention half-time of about 30 days.

Aging↗
PubMed1990

A study on the effects of estradiol and estramustine on gastrointestinal cell lines.

We have studied the effect of estradiol and the combined estradiol/nitrogen mustard compound estramustine on cell lines derived from human gastric and colorectal cancers. Significant stimulation of the two gastric and two fo the colorectal cell lines occurred at physiological concentrations of estradiol. Estramustine showed an inhibitory effect in all of the cell lines at 10 micrograms/l, and a direct dose-dependent inhibition was seen in two of the cell lines. Each of the cell lines was immunohistologically stained using the estrogen-receptor-related protein ERD5, and all of the cell lines except one were positive for this protein. The inhibitory effect of estramustine was lost with increasing concentrations of estradiol, suggesting that the effects of estramustine may be linked to estrogen receptors. We conclude that reduction of circulating levels of estradiol, or treatment with estramustine may have a beneficial effect in the palliation of gastrointestinal malignancy.

Cell Division↗
PubMed1989

The effect of tamoxifen and estrogen receptor status on survival in gastric carcinoma.

One hundred patients were entered in a randomized, controlled study of adjuvant tamoxifen therapy in gastric carcinoma. Estrogen receptor status was established by an immunohistologic method (ERD5) and 55.8% of the tumors were positive. Tamoxifen had no overall effect on survival, but there was a significant decrease in the survival time of the patients with ERD5-positive tumors. Estrogen receptor status (by the ERD5 method) is an independent prognostic factor in gastric cancer. Tamoxifen therapy does not prolong survival, and new therapeutic strategies require investigation.

Clinical Trials as Topic↗