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Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 325 records · Page 18Linked to original sources

Double blind comparative study of omeprazole 10 mg and 30 mg daily for healing duodenal ulcers.

Healing of duodenal ulcers was assessed in 66 patients who received omeprazole either 10 mg or 30 mg daily for four weeks in a double blind study. Healing was rapid in both groups. At two weeks the ulcers in 15 of the 30 patients taking 10 mg daily had healed compared with 28 of the 36 (78%) taking 30 mg daily (p less than 0.03). At four weeks the respective proportions had risen to 83% (25/30) and 94% (33/35) (p greater than 0.05). In non-smokers the proportion of ulcers healed did not differ significantly with the two doses, although there was a trend for less healing at two weeks with 10 mg daily; in smokers significantly fewer ulcers (p less than 0.05) were healed with 10 mg than 30 mg daily at two weeks (7/16 (44%) v 17/21 (81%] and at four weeks (12/16 (75%) v all 21 (100%]. Adverse reactions were few and transient and were considered unlikely to be due to omeprazole.

Adult↗

Scanning electron microscopy of basolateral surfaces of rat renal tubules isolated by sequential digestion.

Renal tubular cells and segments isolated by a trypsin, pepsin, pronase E digestion procedure were studied with scanning electron microscopy. The basal and lateral surfaces of S1, S2, S3 proximal tubular (PT) segments, descending and ascending thin limbs of Henle (TL), distal ascending thick limb of Henle, or distal straight tubule (DST) and distal convoluted tubule (DCT) segments, connecting tubules (CNT), and collecting ducts (CD) were identified and characterized. The basal processes of the S1 and S2 PT cells were fan shaped, were oriented in a circumferential direction, and terminated in microvilli at the basement membrane. S3 PT cells had microvillous basal processes mainly on the lateral edges of the cells. The basal processes of DST and DCT were similar to PT in orientation but terminated on the basement membrane with flattened, thin attachments. The long-loop descending TL and the ascending TL exhibited distinctive interdigitating cell processes. TL segments with simple contours were present in smaller numbers and were characteristic of short-loop descending limbs. CNT showed some cells with basal surfaces resembling DCT cells and others resembling CD cells. Both cortical and medullary CD segments exhibited intercalated cells with round basal contours and a sparse pattern of basal infolding clefts. The cortical CD principal cells revealed a much more elaborate mosaic of plicae, clefts, and microvilli than those of the medullary CD. These observations extend the previous knowledge gained from transmission electron microscopy and assist in the interpretation of that knowledge.

Animals↗

Immunohistochemical findings in rheumatoid nodules.

Eighteen nodules from patients with rheumatoid disease were studied histologically and immunohistochemically. A continuum of microscopic changes was observed with varying degrees of fibrinoid necrosis, mononuclear cell infiltration and healing by fibrous scarring. In two cases there was focal evidence of arteritis. Fibrin was plentiful in the necrotic areas of nodules. Small amounts of immunoglobulin were identified in plasma cells and as irregular extracellular deposits in and around areas of necrosis. In a single small vein abnormal IgG was detected. Mononuclear cells surrounding areas of necrosis stained strongly with antisera to ferritin and a cytoplasmic macrophage antigen, stained variably with muramidase (lysozyme) and negatively with alpha-1 antitrypsin antibodies. Perls' stain for ferric iron was almost entirely negative and ultrastructural x-ray microanalysis indicated that the cytoplasm of these cells were entirely free of iron. These findings confirm the chronic inflammatory nature of rheumatoid nodules but provide no support for the view that they originate in areas of vasculitis. A relative lack of cytoplasmic antiprotease along with a strong expression of ferritin appears to be a characteristic feature of macrophages in rheumatoid tissue.

Adult↗

Differential effect of human chorionic gonadotrophin on lymphocyte proliferation induced by mitogens.

Human chorionic gonadotrophin (hCG) inhibits the lymphoproliferative responses of human peripheral blood mononuclear cells (PBM) to phytohaemagglutinin (PHA) and concanavalin A (Con A) at 10-50 IU of hCG/ml (P less than 0.05). hCG inhibited poorly the response of PBM to pokeweed mitogen (PWM) at concentration up to 100 IU/ml. When monocytes were removed from the PBM population with columns of Sephadex G10 the inhibitory effect of hCG on PHA- and Con A-induced lymphoproliferation was reduced, with inhibition occurring only at a level of 100 IU of hCG/ml. These results suggest that hCG does not inhibit equally the proliferative response of all lymphocyte subsets and further that cells of the monocyte/macrophage series may play a role in its action on lymphocyte proliferation.

Chorionic Gonadotropin↗

Hormonal modulation of human natural killer cell activity in vitro.

This study investigates the effect of steroid and polypeptide hormones on human NK cell activity in vitro. Solutions of hormones were incubated with normal peripheral blood cells in a 4 h cytotoxic assay against the NK-sensitive erythromyeloid cell line K562. The steroid hormones oestradiol, progesterone and testosterone did not exhibit a significant effect on K562 lysis at concentrations within the normal physiological range. HCG and LH, however, had a marked effect on NK activity, the latter at concentrations within the range observed in normal menstruating females.

Adult↗

Omeprazole: a study of its inhibition of gastric pH and oral pharmacokinetics after morning or evening dosage.

Pharmacodynamic and pharmacokinetic studies of omeprazole, a new gastric antisecretory agent, were undertaken in 8 healthy subjects. The drug was administered orally as an encapsulated enteric-coated granulate (40 mg daily at 9 am or 9 pm for 5 days), and its effect on the integrated 24-h gastric pH was determined, together with its apparent bioavailability. The pretreatment 24-h median pH was 1.9 (interquartile range 1.4-2.9). After 5 days of treatment, the median pH had risen to 5.0 (3.7-6.0) (p less than 0.01) with morning dosage and 4.5 (3.0-5.6) (p less than 0.01) with evening dosage. This corresponded to a greater than 99% reduction in 24-h median hydrogen ion activity, with morning dosage having a greater effect (from 9 am to 8 pm) (p less than 0.01) than evening dosage. The relative bioavailability of omeprazole increased twofold from day 1 to day 5 of treatment with morning dosage (p less than 0.02) and threefold with evening dosage (p less than 0.02), suggesting that increased absorption of this acid-labile drug occurs with increasing inhibition of acid secretion. We conclude that this formulation of omeprazole presently being used in clinical trials is a highly potent antisecretory agent in humans, although its optimal effect may not be observed for several days.

Adult↗

Oral acyclovir in the therapy of acute herpes zoster ophthalmicus. An interim report.

A prospective, randomized, double-masked, placebo-controlled clinical trial was conducted to study the effects of oral acyclovir on 55 patients with acute herpes zoster ophthalmicus. Treatment with oral acyclovir resulted in more prompt resolution of signs and symptoms, particularly in patients treated within 72 hours after onset of skin rash (P less than 0.05), and shortened the duration of viral shedding (P = 0.02). Vesicular skin lesions involving other dermatomes (microdissemination) occurred in five (19%) placebo-treated patients but in no acyclovir-treated patients (P = 0.03). Interim analysis of this longitudinal study suggests that the incidence and severity of secondary ocular inflammatory disease was reduced by acyclovir. Prolonged observation of these patients is ongoing to determine if oral acyclovir reduces post-herpes zoster neuralgia or the late ocular complications of ophthalmic zoster.

Acyclovir↗

The prognostic value of the monoclonal antibodies HMFG1 and HMFG2 in breast cancer.

The monoclonal antibodies HMFG1 and HMFG2 identify antigens of the milk fat globule membrane which are also found on breast epithelial cells. Immunohistochemical staining was performed using both antibodies on formalin fixed, paraffin embedded sections of 93 breast carcinoma, 36 histologically benign lesions and 29 histologically normal breast tissue blocks. In both normal and benign breast disease the staining was largely extracellular whilst in malignant tissue the staining was variable and often intracellular. Nine carcinomas did not stain with either antibody. The staining patterns of malignant tissues were graded and no correlation was found between the grades and survival or indices of prognosis, (the oestrogen receptor status, Bloom's grade and the presence or absence of metastases to the axillary nodes.) This study indicates that with the present methods available for grading staining patterns, although of diagnostic value, these monoclonal antibodies are unlikely to assist in determining either the degree of tumour differentiation or prognosis in breast carcinoma.

Antibodies, Monoclonal↗

Angina-like esophageal pain: differentiation from cardiac pain by history.

Consecutive patients coming as an emergency with chest pain due to myocardial ischemia or esophageal disease were interviewed on admission to the hospital, before they had been fully investigated. Classical features of angina pectoris were equally common in both groups and "crescendo angina" was often found in patients with esophageal disease. Features that helped to distinguish esophageal from cardiac pain were: an atypical response to exercise, pain that continued as a background ache, retrosternal pain without lateral radiation, pain that disturbed sleep, and the presence of certain esophageal symptoms. A positive diagnosis will be made more often in cases of suspected but unsubstantiated coronary disease by clinicians who are aware that esophageal pain and angina may be indistinguishable.

Angina Pectoris↗

Factors affecting the secretion of 18-hydroxycortisol, a novel steroid of relevance to Conn's syndrome.

A recently developed radioimmunoassay for direct measurement of 18-hydroxycortisol (18-OH-F) in plasma and urine has been used to study the physiology of this newly described steroid in normal subjects. Plasma levels of 18-OH-F show a circadian variation similar to that of cortisol and are increased and suppressed by administration of ACTH and dexamethasone respectively. A clear increase was observed in response to sodium restriction but despite this, angiotensin II infusion failed to cause a rise in 18-OH-F levels and a possible explanation is discussed. The results are interpreted in terms of a proposed biosynthetic pathway involving 18-hydroxylation of cortisol during a second passage through the adrenal gland.

Adrenal Glands↗

The inhibitory effects of ranitidine and cimetidine on propranolol elimination by the rat isolated perfused liver.

The effect of low (50 micrograms) and high (1 mg) doses of the histamine H2-receptor antagonists cimetidine and ranitidine on the first pass extraction of propranolol was studied in the rat isolated perfused liver. Both low and high dose cimetidine increased the area under the perfusate propranolol concentration time curve (AUC) 4 to 5-fold. Although low dose ranitidine did not alter propranolol AUC, high dose ranitidine increased it to the same extent as cimetidine. These results indicate that ranitidine has a clear propensity for microsomal inhibition, but one which is unlikely to be manifest at therapeutic dosage.

Animals↗

Low-dose guar improves diabetic control.

Twenty diabetic outpatients (12 non-insulin-treated and 8 insulin-treated) were given guar granulate in a dose of 10 g daily for two months in order to study the effect on glycaemic control and lipid levels. Mean glycosylated haemoglobin levels (HbA1c%) fell from 11.1 +/- 2.0% pre-guar to 10.5 +/- 2.2% (P less than 0.001) after one month on guar and to 10.1 +/- 2.3% (P less than 0.0001) after two months. Following discontinuation of guar, HbA1c% rose to 11.1 +/- 2.5% (P less than 0.002). However, there were no significant changes in fasting blood glucose, 1 h postprandial blood glucose following a test meal, 24 h urinary glucose excretion or in lipid levels. Gastrointestinal side effects occurred in 4 patients during treatment with guar. Four patients reduced their dose of insulin and 2 patients reduced their dose of sulphonylurea therapy during this time because of symptoms suggestive of hypoglycaemia. We suggest that the low dose of guar used in this study may help improve glycaemic control in diabetic patients and that this may be achieved with a low incidence of gastrointestinal side effects.

Blood Glucose↗

Differential expression of HLA class II antigens on human fetal and adult lymphocytes and macrophages.

A panel of monoclonal antibodies to monomorphic determinants of the MHC class II subregion locus products: DP, DR and DQ, was used to investigate the expression of these antigens on early lymphocytes and macrophages from human fetal liver (13-20 weeks), placenta (16 weeks and term) and cord blood, in relation to the class II phenotype of cells from adult tonsil and peripheral blood. Fetal liver sections and cell suspensions showed differential expression of class II antigens. DP was expressed at a higher frequency (11.0% of nucleated cells) than DR on lymphoid cells and macrophages from fetal liver, and DQ was either absent or expressed on less than 0.3% of nucleated cells. Consistent with this finding, DP but not DR or DQ antigens were observed on vascular elements and macrophages in the villi of 16-week placenta. At term, all three subregion locus products were expressed. Adult tonsil and peripheral blood B lymphocytes expressed DP, DR and DQ antigens with similar frequency; however, DQ was expressed at a lower frequency than DP and DR on cord blood B lymphocytes. In contrast, 30-50% macrophages from cord blood and adult peripheral blood expressed DP and DR, but fewer (5% and 18%, respectively) expressed DQ. These data suggest that class II antigens are expressed in the sequence DP, DR, DQ on developing lymphocytes. A similar sequence is suggested for macrophages.

Adult↗