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Biomedical subjects

J L Berry

Publications and source records attributed to J L Berry.

At least 55 records · Page 3Linked to original sources

The bronchodilator action of AH 21-132.

The benzonaphthyridine derivative, AH 21-132, has non-specific relaxant effects in isolated airways smooth muscle. The action of AH 21-132 in trachealis muscle is not antagonised by propranolol but AH 21-132 is slightly potentiated by epithelium removal. Electrophysiological recording from guinea-pig trachealis shows that AH 21-132-induced relaxation is accompanied by suppression of electrical slow waves and by cellular hyperpolarisation. Unlike theophylline, AH 21-132 does not cause spasm of cooled (12 degrees C), indomethacin-treated trachealis muscle, nor does it act as an antagonist at adenosine A1 receptors. AH 21-132 does not depress the Ca2+ sensitivity or responsiveness of Triton X-100 skinned trachealis fibres. In tracheal relaxant concentrations, AH 21-132 selectively inhibits cAMP phosphodiesterase (PDE) compared with cGMP-PDE. The (-)-enantiomer of AH 21-132 is more potent than its (+)-enantiomer both in causing tracheal relaxation and in inhibiting cAMP-PDE. When tested on PDE isoenzymes separated from bovine trachealis and guinea-pig cardiac ventricles, AH 21-132 exhibits selectivity as an inhibitor of the isoenzyme types III and IV. AH 21-132 increases the trachealis content of cAMP and cGMP, but only in concentration greater than that required fully to suppress the mechanical tone of the tissue. AH 21-132 has bronchodilator activity in anaesthetised, ventilated guinea-pigs when administered intraduodenally, intravenously or by inhalation. Inhaled AH 21-132 also provides bronchodilatation in healthy human volunteers in whom bronchoconstriction has been induced by inhaled methacholine.

Animals↗

A sensitive radioimmunoassay using a monoclonal antibody that is equipotent for ercalcitriol and calcitriol (1,25-dihydroxy vitamin D2 and D3).

A monoclonal antibody has been used in a sensitive radioimmunoassay that measures 1,25-dihydroxyvitamin D2 (ercalcitriol) and 1,25-dihydroxyvitamin D3 (calcitriol) with equal potency. This important characteristic has not been reported for any other radioimmunoassay for 1,25-dihydroxyvitamin D. The two forms can be assayed in human serum together or individually after HPLC separation. Sample preparation entails acetonitrile extraction followed by C18-Sep-pak chromatography and HPLC. The assay measures 98% of added analyte, and achieves inter- and intra-assay coefficients of variation of 10.7% at 34 pg/ml and 7.8% at 81 pg/ml respectively. The limit of detection is 1.25 pg/tube and 50% displacement of bound ligand is achieved at 14 pg/tube. The reference interval is 20-50 pg/ml, mean 35. The correlation between results from the monoclonal radioimmunoassay and an established polyclonal antibody method was r = 0.98, slope 0.99. The assay has particular application in patients treated with vitamin D2 since 1,25-dihydroxyvitamin D2 can now be measured accurately in the presence of 1,25-dihydroxyvitamin D3.

Antibodies, Monoclonal↗

A comparison of the anticholinergic effects of two formulations of disopyramide in healthy volunteers.

Eight healthy male volunteers took a single oral dose of one of the following: Rythmodan (conventionally formulated disopyramide) 150 mg; Rythmodan 250 mg; Rythmodan Retard (controlled-release disopyramide) 250 mg; placebo. The subjects were allocated double-blind to sessions and treatments according to a Latin square design. In each session pupil diameter, heart rate, salivation, and QT interval were measured immediately before and at 1, 2, 3, 4, 6, 8, and 24 h after the drug. QT interval was corrected for heart rate (QT60). Plasma concentrations of total and unbound disopyramide were also determined at each time point. Both formulations of disopyramide reduced salivary output and increased QT60 interval, but there was not significant difference between the effects of the three active treatments. Neither formulation had any effect on pupil diameter or heart rate. The peak plasma concentration of unbound disopyramide was reached 2 h after Rythmodan and 4 h after Rythmodan Retard. The peak plasma concentration of disopyramide was significantly lower after Rythmodan Retard 250 mg than after Rythmodan 250 mg. The plasma concentration of unbound disopyramide was positively correlated with the reduction in salivation and prolongation of the QT60 interval. The reduction in salivation is likely to reflect blockade of muscarinic receptors by disopyramide, whereas the increase in QT60 interval is likely to be related to a direct effect of the drug on the heart. The results of this single-dose study do not indicate that disopyramide in the controlled-release formulation would be better tolerated by patients than conventionally formulated disopyramide.

Administration, Oral↗

Transpedicular screw fixation.

Spinal fixation employing transpedicular screws has recently been the focus of increased attention at various institutions throughout the world, but concerns about the safety and efficacy of transpedicular screws linger. This study was undertaken to address some of these concerns. The study included evaluation of the internal and external morphology of the vertebral pedicles, which revealed that adequate bone stock is generally available at T2, T7, T12, and L1-L5 spinal levels to accept screws in the 4-7-mm diameter range. The pedicle was observed to be composed of abundant cancellous bone internally with relatively thick cortical walls. The method of pilot hole preparation for pedicle screws was also examined. Screws inserted in pilot holes prepared with a 3.4-mm blunt probe (ganglion knife) resulted in higher pullout forces in eight of 10 trials as compared with those with pilot holes prepared using a 3.2-mm drill. Furthermore, the probes afford greater control of hole depth and alignment. Fatigue studies on three screw designs revealed a graduation of strength between a 7.0-mm pedicle screw, a 5.5-mm pedicle screw, and a modified 6.5-mm cancellous lag screw. The modified cancellous lag screw has an inherent stress riser that affected fatigue life. It was noted that extreme care must be exercised to prevent bending of the pedicle screws during implantation. If bending occurs one can expect a 50% reduction in the number of cycles to failure.

Bone Screws↗

Evaluation of Dacron-covered and plain bovine xenografts as replacements for the anterior cruciate ligament.

Surgical repair of the anterior cruciate ligament often involves the use of a suitable autograft. As alternatives to sacrificing these normal structures, various allografts, xenografts, and synthetic materials have been investigated as ligament replacement materials. This study investigates Dacron fabric-covered and plain bovine xenograft tendon as such materials in the canine knee. The implants were tested to failure in an MTS machine following 13 weeks of implantation in a canine knee. Dacron woven fabric-covered implants became more firmly attached than those covered by Dacron mesh fabric or plain xenografts. The implants were also analyzed according to their method of attachment (fixation staples or sutures). Overall, the sutured implants failed at slightly higher forces than did the stapled ones. Histologically, limited vascular invasion of the xenograft was observed. No host fibrous or osseous tissue could be identified within the graft. Fibrous tissues did form between the bone and xenograft. The implants exhibited extreme intraarticular wear, which suggests a low potential for intraarticular ligament replacement.

Animals↗

Heparinized materials for control of the formation of the laminectomy membrane in experimental laminectomies in dogs.

This study examined the efficacy of heparinized biodegradable materials in the prevention of post-laminectomy scar formation using a canine system. Six-level noncontiguous laminectomies were performed on five adult canines. Exposed dura at each level was covered with the following: (1) nothing (control); (2) fat; (3) fat and autogeneic bone; (4) heparinized Avitene; (5) heparinized Surgicel; or (6) heparinized collagen gel. Canines were killed 16 weeks postoperatively and histologic specimens examined. Fibrous adhesions were abundant at Site 1 (control). Free fat grafts were well preserved and did not permit adhesions at Sites 2 and 3. None of the heparinized materials was as effective as fat in controlling scar formation. Overlying bone at Site 3 did not alter the quality of a free fat graft placed over the dura, a point possibly significant for laminectomies followed by fusion.

Adipose Tissue↗

A morphometric study of human lumbar and selected thoracic vertebrae.

The results of a morphometric study of selected human vertebrae undertaken to provide data for implant design are presented in this report. Twenty-seven dimensions were measured from thoracic (T2, T7, T12) and lumbar (L1-L5) vertebrae using prepared spinal columns from 30 skeletons belonging to the Hamann-Todd Osteological Collection. Maximum and minimum pedicle dimensions indicated that the pedicles are less symmetric cephalad than they are caudal. Vertebral body height increases caudally except posteriorly where, after an initial increase, it decreases in the lower lumbar region. Major and minor body diameters and the major spinal canal diameter slightly increase caudally, whereas minor spinal canal diameter exhibits little or no change.

Female↗

Use of tricalcium phosphate or electrical stimulation to enhance the bone-porous implant interface.

Implant stabilization by biologic ingrowth into a porous surface offers a durable method of prosthetic fixation. These systems, however, lack the immediate stability offered by the use of acrylic bone cement. The interface strength of porous coated Co--Cr--Mo in a canine model does not approach that of acrylic bone cement until two weeks postoperatively. It is expected that this would be a minimum time period in clinical applications. Both chemical and electrical means have been advocated as methods to affect tissue ingrowth. A study using a canine model was undertaken to determine tissue ingrowth rates utilizing examples of these two methods: (1) impregnation of the porous structures with tricalcium phosphate powder (TCP); or (2) the application of an electrical stimulator to the implant with the implant itself serving as the cathode. Ten implants were coated with TCP, two each at weekly intervals from 1 to 5 weeks. Plain porous rods were likewise implanted, serving as the controls. While histology did reveal a slightly more dense bony structure, the interface bond strength was not affected by TCP. Electrical stimulation of the implant was similarly investigated with an additional time period of 10 weeks. Compared to the controls, the electrically stimulated implants reveal no statistically demonstratable difference in interface strength. Histologic specimens indicate larger areas of calcification than are observed in the controls.

Animals↗

Subchondral pathways to the superior surface of the human talus.

The suggestion that the blood supply to subchondral bone plays an active role in the nutrition of adult articular cartilage is a source of controversy. Morphological confirmation of the presence of subchondral defects extending through the basal cartilage layer of the adult human talus is presented. Perfusion of a fluorescent dye through these breaks offers the possibility that they may serve as active pathways for the transport of nutrients to the cartilage. The distribution patterns of the defects in areas of intermittent cartilage loading is noted and its significance is discussed.

Cartilage, Articular↗

A method to prepare bone-implant specimens for laboratory analysis.

A method for the preparation of bone samples containing metallic implants is presented. Technics are detailed for samples to be analyzed by mechanical, microradiographical and microangiographical means, and by tetracycline labeled fluorescent and polarized light microscopy.

Angiography↗

Vitamin D metabolism in patients intoxicated with ergocalciferol.

Vitamin D metabolites were measured on admission in eight patients intoxicated with ergocalciferol (serum calcium 3.01-4.05 mmol/l) and also during the subsequent 2 months in six of the eight. Serum concentrations of 25-hydroxyergocalciferol, on admission, were grossly elevated in all patients (range 583-1843 nmol/l). Serum calcium concentration was related significantly only to the concentration of 25-hydroxyergocalciferol (P = 0.003). Concentrations of 25-hydroxyergocalciferol in serum were significantly related to those of calciferol (P = 0.004). Elevated initial concentrations of 1,25-dihydroxycalciferol, mainly as 1,25-dihydroxyergocalciferol, were found in seven of the eight patients (range 179-313 pmol/l). It is suggested that the hypercalcaemia in these patients may be explained by the action of 25-hydroxyergocalciferol at high concentration in competing for 1,25-dihydroxycalciferol receptors, thus exerting a biological effect per se, and also by increasing the synthesis of 1,25-dihydroxycalciferol through a mass-action effect on the renal 1 alpha-hydroxylase.

25-Hydroxyvitamin D 2↗

Metabolism of vitamin D in patients with primary biliary cirrhosis and alcoholic liver disease.

The metabolism of isotopically labelled vitamin D2 and D3 has been investigated in eight patients with primary biliary cirrhosis and in five controls. The concentration of labelled vitamin D2 was lower than that of vitamin D3 in serum of patients with primary biliary cirrhosis on days 1 and 2 after intravenous injection (P less than 0.005 and P less than 0.05, respectively) but no difference was seen in controls. Similar amounts of labelled 25-hydroxyvitamin D2 and D3 were seen in serum of the control group; the same pattern was observed in the primary biliary cirrhosis group, and no significant differences were observed between the two groups. In both control and primary biliary cirrhosis groups, the serum concentration of labelled 24,25-dihydroxyvitamin D2 exceeded that of 24,25-dihydroxyvitamin D3 (significant for controls on day 2, P less than 0.02) but concentrations in the two groups were not different. Concentrations of labelled 25,26-dihydroxyvitamin D3 were significantly higher than those of 25,26-dihydroxyvitamin D2 in the primary biliary cirrhosis group at all times and in the control group on days 2 and 3. Both 25,26-dihydroxyvitamin D2 and D3 were higher in the serum of patients with primary biliary cirrhosis than in controls (significant on day 1; P less than 0.05). Urinary excretion over days 0-3 of radioactivity from both vitamins D2 and D3 was significantly higher in the primary biliary cirrhosis group than in controls: 12.03 vs 1.80% for vitamin D2 and 8.98 vs 1.76% for vitamin D3 (P less than 0.005). Vitamin D2-derived urinary radioactivity in primary biliary cirrhosis correlated strongly with serum bilirubin (P = 0.005). The metabolism of labelled vitamin D3 was studied in seven patients with alcoholic liver disease, three of whom showed low serum concentrations of labelled 25-hydroxyvitamin D3 suggesting impaired hepatic synthesis. The 25-hydroxylation response was quantified as the relative index of 25-hydroxylation and was significantly related to two other indices of liver function. It is concluded that impaired 25-hydroxylation of vitamin D may occur in alcoholic liver disease and results from hepatocellular dysfunction. Less than the predicted amounts of 1,25-dihydroxyvitamin D3 were produced in four of the seven patients with alcoholic liver disease; this defect may be attributable in part to decreased precursor 25-hydroxyvitamin D and to poor renal function.

Adult↗

Feto-maternal relationships between vitamin D metabolites in Israeli Bedouins and Jews.

The major metabolites of vitamin D, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were assayed in the blood of mothers at delivery and in the cord blood of their infants. Twelve Bedouin women and nine Jewish women were investigated; all lived in the Negev desert in Israel. All three vitamin D metabolites were significantly lower in cord than in maternal blood in both groups. Bedouin mothers and infants had significantly lower levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D than did Jewish mothers and infants. Concentrations of 1,25-dihydroxyvitamin D did not differ significantly between the ethnic groups and in both maternal groups were well above the normal range (Bedouins 83.6 pg/ml +/- 11.3; Jews 98.6 pg/ml +/- 12.3). Cord and maternal values for this metabolite were significantly correlated (r = 0.71, p less than 0.001).

24,25-Dihydroxyvitamin D 3↗

Familial hypocalciuric hypercalcaemia: evidence for continued enhanced renal tubular reabsorption of calcium following total parathyroidectomy.

A patient with familial hypocalciuric hypercalcaemia (FHH) is reported. Seven years after total parathyroidectomy he remained hypocalcaemic, with biochemical evidence of hypoparathyroidism (enhanced renal tubular reabsorption of phosphate, low nephrogenic cyclic AMP excretion, and reduced serum concentration of 1,25-dihydroxycholecalciferol in the presence of normal renal function and normal serum 25-hydroxyvitamin D levels). Iv infusions of calcium were given before and 6 years after total parathyroidectomy. The renal tubular reabsorption of calcium was compared in these two situations. No difference was found. Before and after parathyroidectomy there was enhanced renal tubular reabsorption of calcium. It is concluded that the enhanced renal tubular reabsorption of calcium in FHH is independent of parathyroid hormone. Total parathyroidectomy corrects the hypercalcaemia in FHH by a reduction in the input of calcium into the extra-cellular fluid from gut and or bone perhaps as a result of reduced renal synthesis of 1,25-dihydroxycholecalciferol.

Adolescent↗

Ultraviolet irradiation increases serum 1,25-dihydroxyvitamin D in vitamin-D-replete adults.

The production of vitamin D metabolites in response to ultraviolet irradiation has been studied in 5 control subjects and 8 patients with psoriasis; both groups responded similarly. Significant increases within the normal range were observed for serum 1,25-dihydroxyvitamin D; these increases were negatively related to the initial concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. Serum 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D increased linearly over the 21 days of study, the production of 25-hydroxyvitamin D being negatively correlated with its own initial concentration. The changes in vitamin D metabolism were accompanied by significant rises within the normal ranges in serum inorganic phosphorus and in urinary calcium. These results indicate the variation of 1,25-dihydroxyvitamin D occurs in vitamin-D-replete adults and that this variation is probably responsible for the observed alterations in calcium and phosphorus metabolism.

Adult↗

Vitamin D state of Asians living in Pakistan.

Asians living in Pakistan have serum 25-hydroxycholecalciferol concentrations which are well within the normal range and significantly higher than in Asians resident in Britain. Clearly, Asians can maintain an adequate vitamin D state given an abundant supply of ultraviolet light, and the expression of vitamin D deficiency is an environmental and not a genetically determined characteristic. The risk of an Asian developing vitamin D deficiency increases after migration to Britain. The most efficient way to treat this is by supplementation with vitamin D.

Adolescent↗

Vitamin D deficiency, osteomalacia, and primary biliary cirrhosis. Response to orally administered vitamin D3.

Five patients with primary biliary cirrhosis and vitamin D deficiency (serum 25-hydroxyvitamin D less than 6 ng/ml) are presented. All patients had low serum 24,25-dihydroxyvitamin D3 concentrations. Three patients had histological osteomalacia, negative calcium balance, and subnormal serum 1,25-dihydroxyvitamin D3. Malabsorption of a standard dose of [3H]vitamin D3 was found in three of four patients with steatorrhea, enabling the effective dose of vitamin D3 given to be calculated. Oral vitamin D3 400-4000 IU/day (effectively 400-1860 IU/day) resulted in a return to normal of the serum vitamin D metabolites, correction of the impaired intestinal calcium absorption and healing of the osteomalacia. Increases in serum calcium, phosphate, and the renal tubular reabsorption of phosphate occurred with a concomitant decrease in serum parathyroid hormone. It is suggested that osteomalacia in primary biliary cirrhosis is the end result of vitamin D deficiency; the hepatic and renal hydroxylations of vitamin D are normal and target tissues are responsive to endogenously produced metabolites of vitamin D.

Administration, Oral↗