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Biomedical subjects

A Parkin

Publications and source records attributed to A Parkin.

At least 37 records · Page 2Linked to original sources
PubMed1994

Bioisosters of the diphosphate group in activated forms of antiherpes virus agents. A theoretical study.

In order to identify potential bioisosteric replacements for the diphosphate moiety, which is present in activated forms generated from antiherpes virus agents during their inhibitory action against herpes viruses, 5'-phosphonoacetamido (4) and 5'-O-sulfamoylcarbamoyl (5) derivatives of idoxuridine were synthesised as analogues of idoxuridine 5'-diphosphate (6). In this paper we report on the antiherpetic activity of 4 and 5. Moreover, a theoretical study is presented in which both the conformational and the electronic characteristics of 4 and 5 are compared with those of the diphosphate metabolite of idoxuridine (6), in order to verify the possibility of bioisosterism relationship between the phosphonoacetamido, the sulfamoylcarbamoyl and the diphosphate group.

Antiviral Agents↗
PubMed1993

Novel acyclonucleotides: synthesis and antiviral activity of alkenylphosphonic acid derivatives of purines and a pyrimidine.

A series of phosphonoalkenyl and (phosphonoalkenyl)oxy derivatives of purines and a pyrimidine were synthesized. These compounds are the first reported acyclonucleotides which incorporate the alpha,beta-unsaturated phosphonic acid moiety as the phosphate mimic and include compounds in which the acyclic substituent is attached to N-9 of a purine or N-1 of a pyrimidine by either a nitrogen-carbon or a nitrogen-oxygen bond. The phosphonoalkenyl-substituted compounds 7a-c, 8a-c, 9, 10, and 12 were prepared either by Mitsunobu coupling of alcohols with purine or pyrimidine derivatives or by alternative alkylations of the heterocyclic bases. The (phosphonoalkenyl) oxy derivatives 7d-g, 8d-g, and 11 were synthesized by coupling of alcohols with 9-hydroxypurines or a 1-hydroxypyrimidine under Mitsunobu conditions. The novel acyclonucleotides were tested for activity against herpes simplex types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), visna virus, and human immunodeficiency virus type 1 (HIV-1). Guanine derivatives were moderately to extremely cytotoxic, but the adenines were less toxic to cells. At the concentrations tested, (Z)-isomers in the unbranched series had no activity against herpes viruses or HIV-1. (E)-9-[(4-Phosphonobut-3-enyl) oxy]adenine (7d) displayed selective activity against HIV-1, (E)-2,6-diamino-9-(4-phosphonobut-3-enyl) purine (9) showed selective antiretrovirus activity, and (E)-9-[2-(hydroxymethyl)-4-phosphonobut-3-enyl]adenine (7c) showed selective antiherpesvirus (VZV and CMV) activity.

Antiviral Agents↗
PubMed1993

Antiherpes virus agents: a review.

In this review, after some considerations about the structure of the virus and the viral replicative cycle, herpes virus diseases in man are described. The most important antiherpes virus drugs until now discovered are then reported analyzing and examining their chemical structure related to their mechanism of action and their pharmacological activity. Finally, defects of antiherpes virus drugs currently in therapy are shown, in order to outline which directions future developments will have to follow.

Animals↗
PubMed1992

An analysis of a radionuclide technique used to measure reactive hyperaemia in limbs.

A radionuclide technique (PT) for measuring the blood flow to a limb during reactive hyperaemia is described and analysed. Patients are positioned with lower limbs within the field of view of the gamma camera and pneumatic cuffs are placed below the knees to isolate the blood and induce a hyperaemic response. The remaining blood pool is labelled with 99Tcm-human serum albumin. Following release of the occlusion the rate of inflow to the limb of the radionuclide is measured and hyperaemic flow then determined, during the initial phase of the hyperaemia. The results may be analysed using a single compartment to represent the vascular pool in the lower limb. During the initial phase, activity entered the pool at a constant rate from which the blood flow may be calculated. Results were obtained in a group of 20 normal control volunteers and 20 patients with occlusive arterial disease. They indicate that following release of the cuff the blood flow rises rapidly (within 1-2 s) to a constant value which is maintained for at least 10-12 s in normal subjects and a longer period in arteriopaths. The mean flow in the normal group was 14.4 ml/100 ml min-1 and in the arteriopathic group was 4.6 ml/100 ml min-1. The constant flow measured by PT during the initial phase of reactive hyperaemia appears to differ from the results of venous occlusion plethysmography and washout of a freely diffusible tracer and possible reasons for these differences are discussed.

Adult↗
PubMed1992

Hepatic perfusion index: a multicentre trial.

The reproducibility and accuracy of the hepatic perfusion index (HPI) was examined by consideration of in vitro and in vivo factors. A phantom was used to simulate liver blood flow and data acquired on nine gamma cameras. Dynamic hepatic scintigraphy was undertaken on 28 patients at two centres and values obtained for the HPI. Results from the phantom study showed good agreement between the nine cameras and also with the HPI values predicted from the measured phantom flow rates. The results of the patient study indicated a high degree of conformity between observers (r = 0.95, S.E = 0.03) but poorer correlation between the HPI values from the two centres (r = 0.67, S.E. = 0.09). These results imply that centres wishing to use HPI clinically should establish their own range of normality.

Blood Flow Velocity↗
PubMed1991

24-hour survival of autotransfused red cells in elective aortic surgery: a comparison of two intraoperative autotransfusion systems.

Twelve patients undergoing elective aortic surgery had intraoperative autotransfusion using either the Haemonetics Cell Saver or the Solcotrans device. The 24-h post-transfusion survival of the patients' preoperative red cells, labelled with indium-111, was compared with the survival of salvaged red cells labelled with chromium-51. A correction coefficient for the instability of the indium-111 label was calculated from the study of red cell survival in six healthy volunteers. There was no significant difference in the volume of circulating red cells measured using each isotope, indicating that extensive early destruction of the autotransfused red cells does not occur. The percentage survival of autotransfused red cells at 24 h was similar to that of the red cells that had not undergone salvage. Both devices were comparable with respect to the effects of cell salvage on the 24-h survival rate of autotransfused red cells.

Aortic Diseases↗
PubMed1991

The effect of cyclosporin on lower limb blood flow in renal transplant recipients.

We investigated the effect of electively converting stable renal allograft recipients from cyclosporin A (CyA) to prednisolone and azathioprine on limb blood. We used a non-invasive method designed to measure the hyperaemic blood flow to the lower limb following a standard ischaemic insult. The hyperaemic blood flow was greater during CyA therapy--median 14 ml/100 ml tissue per minute (95% confidence limits 10.5-16.5)--than that after conversion--median 11 ml/100 ml tissue per minute (8.3-13.8; P less than 0.01). By increasing peripheral vascular resistance and reducing limb blood flow, CyA may have caused an increase in the degree of ischaemia, so resulting in a greater hyperaemic response.

Adult↗
PubMed1991

Isotope limb blood flow measurement in patients undergoing peripheral laser angioplasty.

A technique of isotope limb blood flow (ILBF) measurement employing Technetium-labelled human albumin and a gamma camera, was used to assess limb perfusion in 19 patients undergoing percutaneous laser angioplasty, both before and one month after treatment. Twenty-three limbs with femoro-popliteal occlusions ranging in length from 3-35 cm (median 8 cm) were recanalized using an Nd-YAG laser and sapphire tipped optical fibre. Primary angiographic success was achieved in 19 lesions of which 6 re-occluded within the first month, and 13 remained patent with relief of symptoms. Clinically successful procedures were associated with a large increase in ILBF. However, normal blood flow was restored in only 54% of limbs. There was a slight decrease in limb perfusion after failed laser angioplasty but this was not statistically significant in this small series. Furthermore, there was no clinically apparent circulatory compromise, or need for urgent surgical bypass in failed cases. We conclude that ILBF is a useful means of assessing patients undergoing laser angioplasty, particularly for detecting small flow changes in patients who are unable to complete a standard exercise test. Its use can be recommended for assessing blood flow changes following other forms of limb revascularization.

Aged↗
PubMed1991

Comparing subjective and objective assessments of the severity of vibration induced white finger.

The present staging of the disease severity of vibration induced white finger (VWF) is based on the patients' symptoms. Forty patients, with a history of VWF, with disease severity stage III or stage IV, on the Taylor-Pelmear scale, were investigated. Total, reactive hyperaemic blood flow to the hands was measured using an isotope limb blood flow (ILBF) technique. Skin blood flow patterns were assessed using a cold provocation test, followed by thermographic assessment of hand rewarming. Thermographic abnormalities were detected in 39 patients (97%). Decreased post-occlusive, reactive hyperaemic blood flow occurred in 29 patients (73%). There was no difference in skin blood flow patterns or in total hand blood flow between the stage III and stage IV groups. Reduction of postocclusive reactive hyperaemic blood flow may be indicative of occlusive lesions of the digital vessels. We conclude that the classification of the severity of VWF using subjective assessment, needs to be augmented by objective evidence of altered blood flow.

Adult↗
PubMed1991

Synthesis and antiviral activity of 9-alkoxypurines. 2. 9-(2,3-Dihydroxypropoxy)-, 9-(3,4-dihydroxybutoxy)-, and 9-(1,4-dihydroxybut-2-oxy)purines.

Reaction of alkenoxyamines (3,5) or (R,S)-, (R)-, and (S)-hydroxy-protected derivatives of hydroxyalkoxyamines (20a,b, 37a-c) with 4,6-dichloro-2,5-diformamidopyrimidine (4) and cyclization of the resultant 6-[(alkenoxy)amino]-and 6-(alkoxyamino)pyrimidines (6,7,21a,b, 38a,b,c) by heating with diethoxymethyl acetate afforded 9-alkenoxy- and 9-alkoxy-6-chloropurines (9,10,22a,b, 39a-c, 40a). These were subsequently converted to 9-(2,3-dihydroxypropoxy), 9-(3,4-dihydroxybutoxy), and 9-(1,4-dihydroxybut-2-oxy) derivatives of guanine and 2-aminopurine (13-16, 25-28, 41a-c, 42a). A 2-amino-6-methoxypurine derivative (17) was also prepared. The racemic guanine derivative 13 showed potent and selective activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), but was less active against varicella zoster virus (VZV). Its antiviral activity is attributable to the S isomer (28), which was found to be more active than acyclovir against HSV-1 and HSV-2 and about 4 times less active than acyclovir against VZV. The S enantiomer of 9-(1,4-dihydroxybut-2-oxy)guanine (41c) also showed noteworthy antiviral activity in cell culture. Although this acyclonucleoside (41c) is only weakly active against HSV-1 and inactive against HSV-2, it is about twice as active as acyclovir against VZV.

Antiviral Agents↗
PubMed1991

Radionuclide limb blood flow in peripheral vascular disease: a review of 1100 measurements.

Radionuclide limb blood flow measurements using 99Tcm-labelled human serum albumin and a gamma camera have been performed on normal volunteers and on patients with suspected or confirmed peripheral arterial disease. The normal range of flow was found to be 10.0-22.3 ml per 100 ml tissue per min. Flow in the symptomatic legs of patients with arterial disease varied from 9.0 ml per 100 ml tissue per min in mild claudication to less than 1.0 ml per 100 ml tissue per min in rest pain. The technique has been used as an initial screening procedure, to resolve diagnostic problems, to measure objectively the treatment response and to assess patients with critical ischaemia. The results of 1100 measurements are reported and the clinical utility in routine vascular surgical practice is discussed.

Adult↗
PubMed1990

Dual tracer technique to measure salvaged red cell survival following autotransfusion in aortic surgery.

The survival of autotransfused red cells was measured for two salvage devices used in 12 elective aortic reconstructions. Six patients underwent cell salvage with the Solco-trans device and six with the Haemonetics cell saver. A double tracer technique was used to take account of post-operative blood loss and fluid replacement. Comparison was made with the results of a group of normal volunteers. A comparison was made of the labelling efficiency of damaged and undamaged red cells using chromium to check that red cells damaged during autotransfusion can be labelled. No significant difference was seen. There was no significant difference in red cell survival between the volunteer group and either of the two salvage device groups. These results suggest that red cell survival is not compromised by the autotransfusion process using these two devices.

Aortic Diseases↗