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Biomedical subjects

H Hart

Publications and source records attributed to H Hart.

At least 37 records · Page 2Linked to original sources

Distribution of hepatitis A antibody over a process for the preparation of a high-purity factor VIII concentrate.

The levels of hepatitis A antibody were studied in factor VIII products manufactured by the Scottish National Blood Transfusion Service. It was found that the current high-purity factor VIII product has no detectable hepatitis A antibody, whereas the superseded intermediate-purity product had significant antibody levels (6,700 mIU/ml). Although the finished high-potency factor VIII product has no detectable hepatitis A antibody, significant levels of antibody are found in the early stages of product manufacture. This antibody may offer some protection against hepatitis A contamination present in very occasional plasma donations. Antibody to parvovirus B19 is also present at intermediate stages in the manufacture of high-potency factor VIII, but its significance is not known. Hepatitis A antibody levels were also measured in normal immunoglobulin. These data indicate that antibody levels in the plasma pools used to manufacture factor VIII are falling.

Consumer Product Safety↗

Anti-inflammatory activity of hamamelis distillate applied topically to the skin. Influence of vehicle and dose.

The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle. UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P < or = 0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry. The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity.

Administration, Topical↗

A comparison of polymerase chain reaction and an infectivity assay for human immunodeficiency virus type 1 titration during virus inactivation of blood components.

Three examples of human plasma-derived concentrates, intermediate-purity factors VIII and IX, and fibrinogen were spiked with tissue culture-grown human immunodeficiency virus type 1 (HIV-1) strain RF. All examples were freeze-dried and heated at 80 degrees C for 72 hours by using validated production process models. HIV-1 infectivity was measured by a syncytial infectivity assay in C8166 cells and then compared with levels determined by nested HIV polymerase chain reaction (PCR). The infectivity assay demonstrated a reduction index of at least 4.5 log10, while PCR showed an average 1.7 log10. Large amounts of HIV-1 RNA (10(5)) were still detectable by PCR in samples in which infectivity assays failed to detect any HIV-1. These data suggest that HIV-1 PCR levels do not parallel HIV-1 infectivity levels during virus-inactivation procedures involved in coagulation factor concentrate production. PCR was able to detect the RNA associated with inactivated HIV-1 particles in the factor concentrates, which allows the conclusion that PCR is not a useful test with which to monitor virus-inactivation procedures such as heating at 80 degrees C for 72 hours. This judgment contrasts with the more definite and sensitive role of PCR in diagnosing HIV-1 infection in patients in whom a positive HIV-1 PCR result correlates with active HIV-1 infection and with PCR's usefulness in monitoring virus removal.

DNA, Viral↗

Inactivation of viruses during ultraviolet light treatment of human intravenous immunoglobulin and albumin.

A comparison of ultraviolet (UV) irradiation of two wavelength ranges UVB (280-320 nm) and UVC (lower than 280 nm) showed that UVC in particular could very effectively inactivate, in intravenous immunoglobulin (IVIG) and albumin preparations, non-enveloped and non-acid labile model viruses (i.e., Polio 2 and T4 phage) and dry heat-resistant viruses (vaccinia and T4 phage). This effective virucidal treatment (5 min, 5,000 J/m2 dose) was achieved before an unacceptable level of IVIG aggregates occurred. The use of UV irradiation to inactivate infectious agents could add safety and supplement current methods, e.g. solvent/detergent, low pH, which do not inactivate non-enveloped, non-acid labile or dry-heat-resistant viruses at present.

Antibodies, Viral↗

Detection of parvovirus B19 in donated blood: a model system for screening by polymerase chain reaction.

A highly sensitive and rapid method for routinely screening large numbers of donated blood units for parvovirus B19 by the polymerase chain reaction (PCR) was developed. Over a 3-month trial period in Edinburgh, B19 DNA was detected in 6 of 20,000 consecutive units of blood (0.03%), in concentrations ranging from 2.4 x 10(4) to 5 x 10(10) copies of viral DNA per ml. Seroconversion for B19-specific immunoglobulin M and immunoglobulin G and disappearance of circulating B19 DNA occurred in the interval between donation and recall in four of the five implicated donors who could be recalled. B19 DNA was detected in 18 of 27 separate batches of non-heat-treated factor VIII and IX concentrate manufactured from donated plasma unscreened for B19 DNA. Dry-heat treatment at 80 degrees C for 72 h reduced but did not always eliminate detectable B19 from factor VIII concentrates, consistent with recent observations that current methods for virus inactivation during blood product manufacture are insufficient to entirely eliminate B19 infectivity. The methods developed in this study for PCR screening could be applied routinely to prevent transfusion of B19 in blood and blood products and could play an important role in the prevention of iatrogenic transmission of infection. PCR screening could also be used for detection and exclusion of a range of other transmission-associated viruses for which current serological detection methods are only partially effective.

Base Sequence↗

Use of recombinant human parvovirus B19 antigens in serological assays.

AIMS--To compare the sensitivity, specificity, and practicality of recombinant proteins in serological tests for the detection of human parvovirus B19 IgG and IgM. METHODS--Indirect enzyme linked immunosorbent assays using B19 structural proteins expressed in Escherichia coli were developed for the detection of B19 specific IgG and IgM (rELISA-G and rELISA-M). Cells infected with baculovirus expressing B19 structural proteins were also used in an indirect immunofluorescence assay for IgG and IgM antibodies (IFA-G and IFA-M). Antibody capture radioimmunoassays for IgG and IgM (GACRIA and MACRIA) were used as comparative assays. RESULTS--Twenty nine pools of intravenous immunoglobulin were clearly positive for B19 IgG by rELISA-G and contained low IgG titres by GACRIA. From 113 samples tested by all methods, sensitivities of 92% (77/84) and 97% (68/70) were obtained for ELISA and immunofluorescence, respectively, when compared with GACRIA. One hundred and sixteen samples from patients presenting with rash or arthralgia were compared by MACRIA, rELISA-M, and IFA-M. Sensitivities of both recombinant tests were more than 95%. Despite pretreatment to remove IgG or rheumatoid factor, false positive results were a problem in the rELISA-M but were not seen with the IFA-M. CONCLUSIONS--The limited supply of native antigen has severely restricted the wide application of serology for parvovirus B19. The use of recombinant antigens permitted the introduction of local screening tests which had many advantages, including quicker results and relief of the burden on the Reference Laboratory. The use of rELISA-M for sensitivity and IFA-M for specificity and confirmation proved a useful and practical combination for diagnosis of recent infection with B19, and rELISA-G allowed the immune response to be determined in selected populations.

Adolescent↗

Early prevention of left ventricular dysfunction after myocardial infarction with angiotensin-converting-enzyme inhibition.

Left ventricular dysfunction can be improved with angiotensin-converting-enzyme inhibition started 1 week after myocardial infarction or later. To see whether earlier intervention may confer greater benefit, a double-blind study was carried out in which 100 patients with Q wave myocardial infarction, but without clinical heart failure, were randomly allocated treatment with captopril 50 mg twice daily or placebo starting 24-48 h after onset of symptoms. Left ventricular volumes were measured regularly during 3 months of treatment and after a 48 h withdrawal period by means of two-dimensional echocardiography. The placebo group showed significant increases in left ventricular end-diastolic (LVEDVI) and end-systolic (LVESVI) volume indices, with the ejection fraction unchanged. By contrast, the captopril group showed a slight but not significant rise in LVEDVI and a significant reduction in LVESVI with ejection fraction increased significantly. At 3 months there was a 4.6% difference in the change in ejection fraction from baseline between the groups (p less than 0.0001). Most of the treatment benefit was evident at 1 month and there were no changes in left ventricular volumes after 48 h withdrawal of treatment at 3 months. Heart failure requiring treatment with frusemide developed in 7 patients in each group during the study period; 3 of these (1 captopril-treated, 2 placebo-treated) had to be withdrawn from the trial with severe heart failure requiring open treatment. Thus early treatment with captopril is effective in preventing the ventricular dilatation that can occur after Q wave myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

A study of the experience of Glasgow women in the climacteric years.

Overall, 424 women between 40 and 60 years of age were interviewed with reference to their experience of the menopause; 179 (42%) expressed a 'need for treatment' which was more marked in those who had had a hysterectomy (57%) or oophorectomy (76%). Of those who sought help (174) a large majority (92%) had seen their general practitioner and 72% received some form of drug therapy, predominantly hormone replacement therapy (HRT) or psychotropic drugs. Twenty-eight women were currently having HRT (7%) and 39 (9%) had previously had HRT. Only 12 women (3%) had received greater than 3 years of HRT and nine of these had had an oophorectomy. Only 1% of other women were 'long-term' users of HRT. Of the 424 women 11% expressed dissatisfaction with their general practitioner's approach to this subject.

Adult↗

Study and performance evaluation of statistical methods in image processing.

Two statistical image processing formalisms involving the entropy concept and Bayesian analysis are studied. Iterative imaging algorithms of the formalisms are formulated by employing, for the purpose of performance evaluation and easy implementation, the steepest descent method for the solution of entropy concept and the expectation maximization technique for the solution of Bayesian analysis. Quantitative evaluation and comparison of the convergence performance of the iterative algorithms on computer generated ideal and experimental radioisotope phantom imaging noisy data are given. The study concludes that the entropy algorithm can converge relatively fast, but it is very sensitive to noise in measured data due to the ill-posed nature of inverse problems and its lack of ability to consider the statistics of data fluctuation; while the Bayesian algorithm converges monotonically even with noisy data and has the advantage of considering both the a priori source distribution information and the statistical fluctuation of measured data.

Algorithms↗

Identification and expression of a human cytomegalovirus glycoprotein with homology to the Epstein-Barr virus BXLF2 product, varicella-zoster virus gpIII, and herpes simplex virus type 1 glycoprotein H.

An open reading frame with the characteristics of a glycoprotein-coding sequence was identified by nucleotide sequencing of human cytomegalovirus (HCMV) genomic DNA. The predicted amino acid sequence was homologous with glycoprotein H of herpes simplex virus type 1 and the homologous protein of Epstein-Barr virus (BXLF2 gene product) and varicella-zoster virus (gpIII). Recombinant vaccinia viruses that expressed this gene were constructed. A glycoprotein of approximately 86 kilodaltons was immunoprecipitated from cells infected with the recombinant viruses and from HCMV-infected cells with a monoclonal antibody that efficiently neutralized HCMV infectivity. In HCMV-infected MRC5 cells, this glycoprotein was present on nuclear and cytoplasmic membranes, but in recombinant vaccinia virus-infected cells it accumulated predominantly on the nuclear membrane.

Amino Acid Sequence↗

Do polyclonal rheumatoid factors carry an 'internal image' of cytomegalovirus, Epstein-Barr virus and nuclear antigens?

Rabbit antisera have been prepared against isolated rheumatoid factors (RF's). It was considered that RFs are anti-idiotype antibodies and that the anti-RF antisera had anti-anti-idiotype specificity. Furthermore, it was considered that the RF's carry an "internal image" of the putative "antigen X" and that the rabbit antisera would have specificity for this "antigen-X". Reactions of the rabbit antisera with the early and late antigens of CMV, EBV antigens and nuclear antigens suggest that there may be an "internal image" of these antigens in rheumatoid factor molecules and that they all may be related to the immunogenesis of RF.

Animals↗

Fine structure of cells infected with human cytomegalovirus after treatment with 9-(1,3-dihydroxy-2-propoxymethyl)guanine.

Infection with human cytomegalovirus (CMV) is characterized by cytological changes which are readily visualized by electron microscopy using ultrathin sections of infected cells. Treatment of such cells with 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), a potent inhibitor of CMV, is effective when initiated at early or late times after infection and the response to such treatment has been studied by fine structural analysis. Inhibition of viral DNA synthesis by DHPG treatment (50 microM) late in virus infection resulted in a cessation of virus growth accompanied by a lack of development and possible regression in skein-like intranuclear inclusions together with a depletion in cytoplasmic dense bodies. Such changes were accompanied by the appearance of nuclear dense bodies. These were also present when virus growth was reduced (5 microM-DHPG) rather than completely inhibited (50 microM-DHPG) by treatment initiated from the time of infection. The nuclear bodies were predominantly of a reticular type structure after the early treatment but mainly of a homogeneous form when virus growth was interrupted at late times. Their presence appeared to be connected with the ability of infected cells to initiate the synthesis of late proteins and their morphology may relate to the extent of such protein synthesis. Unlike cytoplasmic dense bodies, provisional findings on the characterization of the nuclear bodies suggested that the 69K matrix protein was not present in abundance.

Acyclovir↗

[Effectiveness of various immunoglobulin preparations administered by the intravenous route in peritonitis in the rat model].

Intraabdominal sepsis in rats was induced as a sublethal infection (mortality rate of controls: 60%-80%) and as a lethal infection (mortality rate of controls: 100%). The effectivity of different immunoglobulin (IgG) preparations alone or together with an antibiotic combination therapy (gentamicin + piperacillin) was then tested. In sublethal infection, 5 intravenous administrations of three 7S-IgG preparations and a plasmin-treated preparation at a dosage of 0.5 g/kg b.w. were able to reduce lethality only slightly, whereas a 5S-IgG preparation was able to reduce lethality by 30% significantly. Intraperitoneal administration of two 7S-IgG preparations (s-sulfitolysis, 42 degrees C/ammonium sulfate) and the 5S-IgG preparation reduced lethality to 27%, 37% and 47%, respectively, whereas another 7S-IgG (iodoacetamide/dithiothreitol) and a plasmin-treated preparation failed to reduce lethality significantly. The convincing results obtained with the 5S-IgG preparation are probably due to the fact that Fc-mediated side-effects could be avoided. The better effectivity of intraperitoneal compared to intravenous administration can be explained by much higher concentrations of specific antibodies at the site of infection. In the lethal infection model the mortality of animals treated with antibiotics only was 50%. The additional intravenous administration of 7S-IgG (42 degrees C/ammonium sulfate), a plasmin-treated preparation and a 5S-IgG was unable to reduce mortality any further. These findings are in contrast to several publications which postulate synergism of antibiotics and immunoglobulins.

Animals↗

Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralizing antibodies via its expression in recombinant vaccinia virus.

A human cytomegalovirus (HCMV) glycoprotein gene with homology to glycoprotein B (gB) of herpes simplex virus and Epstein-Barr virus and gpII of varicella zoster virus has been identified by nucleotide sequencing. The gene has been expressed in recombinant vaccinia virus and the gene product recognized by monoclonal antibodies and human immune sera. Rabbits immunized with the recombinant vaccinia virus produced antibodies that immunoprecipitate gB from HCMV-infected cells and neutralize HCMV infectivity in vitro. These data demonstrate a role for this protein in future HCMV vaccines.

Amino Acid Sequence↗

[Effects and side effects of taurolin in experimental peritonitis in the rat].

Taurolin (2%) was tested in a peritonitis in the rat. In a control group without treatment the mortality was 63% 80 h after infection. Intraperitoneal application of taurolin did not change this mortality rate but delayed the mortality by 8 h. Intravenous administration of taurolin increased mortality to 87%. In a second experimental protocol the dosis of bacteria was increased and 100% of the animals died within 16 h. Gentamicin-Piperacillin therapy reduced the mortality to 50%. With taurolin this effect of antibiotics could not be improved. In both groups taurolin was not able to reduce toxic lung edema. With these results and the knowledge of the literature taurolin cannot be recommended for clinical use.

Animals↗

Temporomandibular joint: magnetic resonance imaging.

Magnetic resonance (MR) imaging of the temporomandibular joint was performed in two subjects using a 1.5 T experimental imaging system equipped with a 6.5 cm surface coil antenna. Normal and pathologic anatomy were demonstrated with exquisite detail. Anterior displacement of the joint meniscus was clearly visible in the symptomatic subject, consistent with arthrographic confirmation.

Adult↗

Surface-coil magnetic resonance imaging of the internal auditory canal.

Computed tomography is effective for detecting acoustic neuromas, but not for resolving individual nerves in the internal auditory canal. Surface-coil magnetic resonance (MR) images of the internal auditory canal were obtained using a 1.5 T superconducting magnet, a 13.5-cm-diameter surface coil, 3- and 5-mm-thick slices, and partial-saturation pulse sequences. Cranial nerves VII and VIII (three branches) were identified on MR images in volunteers and on corresponding cryomicrotomic sections. The nerves were obscured in one patient with an acoustic neuroma. Because high-resolution surface-coil images can demonstrate specific nerves in the internal auditory canal, MR should be a sensitive study to evaluate cranial nerves VII and VIII in patients with facial paralysis and neurosensory hearing loss that is congenital or caused by small acoustic neuromas.

Facial Nerve↗