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Biomedical subjects

H Bull

Publications and source records attributed to H Bull.

At least 19 recordsLinked to original sources

Basing policy on evidence: low HIV, STIs, and risk behaviour in Dili, East Timor argue for more focused interventions.

BACKGROUND: East Timor is a newly independent, poor nation with many internally displaced people and foreign peace keeping forces. Similarities with Cambodia, which now has Asia's worst HIV epidemic, caused donors to earmark money for HIV prevention in East Timor, but no data were available to plan appropriate programmes. OBJECTIVES: To determine levels of infection with HIV and other sexually transmitted infections (STIs) and associated risk behaviours in Dili, East Timor, in order to guide resource allocation and appropriate prevention and care strategies. METHODS: In mid-2003, a cross sectional survey of female sex workers, men who have sex with men (MSM), taxi drivers, and soldiers was conducted. Participants provided biological specimens and all answered structured questionnaires. RESULTS: HIV prevalence was 3% among female sex workers (3/100), 0.9% among MSM (1/110), and zero in the other groups. All the HIV infected sex workers reported sex with foreign clients. Partner turnover reported by all groups was among the lowest in Asia, so was condom use. Access to basic HIV prevention services, including condoms and STI services, was extremely low in all groups. CONCLUSIONS: A few sex workers are infected with HIV in East Timor, but the virus is not circulating widely among their clients, and sexual networking is limited. The risk of a generalised HIV epidemic in East Timor is minimal. HIV can be contained by the provision of basic services to the small minority of the population at highest risk, preserving resources for other health and development needs.

Adult↗

Acid phosphatases.

Acid phosphatases (APs) are a family of enzymes that are widespread in nature, and can be found in many animal and plant species. Mystery surrounds the precise functional role of these molecular facilitators, despite much research. Yet, paradoxically, human APs have had considerable impact as tools of clinical investigation and intervention. One particular example is tartrate resistant acid phosphatase, which is detected in the serum in raised amounts accompanying pathological bone resorption. This article seeks to explore the identity and diversity of APs, and to demonstrate the relation between APs, human disease, and clinical diagnosis.

Acid Phosphatase↗

Viscocanalostomy for primary open-angle glaucoma: the Gross Pankow experience.

PURPOSE: To assess the pressure-lowering effect and postoperative complications of the viscocanalostomy nonpenetrating filtering procedure. SETTING: A private practice ophthalmic surgery referral center. METHODS: Fifty-six eyes of 41 patients with medically uncontrolled primary open-angle glaucoma had a viscocanalostomy. After a superficial scleral flap was raised, a deep sclerectomy was performed in the scleral bed with deroofing of Schlemm's canal and preparation of a window of Descemet's membrane. The ostia of Schlemm's canal were probed and stretched with sodium hyaluronate 1.4% (Healon GV(R)), and the scleral flap and conjunctiva were sutured. Examinations were performed before surgery and 1, 3, and 14 days and 1, 3, 6, and 12 months postoperatively. RESULTS: Mean preoperative intraocular pressure (IOP) was 28.1 mm Hg +/- 7.4 (SD) with a mean of 2.4 +/- 0.7 medications. Mean postoperative IOP was 18.6 +/- 7.5 mm Hg with 0 medications at 1 day, 17.4 +/- 5.2 mm Hg with 0.1 medications at 3 days, 19.1 +/- 4. 3 mm Hg with 0.1 medications at 14 days, 19.4 +/- 4.3 mm Hg with 0.4 medications at 1 month, 18.3 +/- 3.6 mm Hg with 0.6 medications at 3 months, 18.0 +/- 2.6 mm Hg with 0.6 medications at 6 months, and 17. 8 +/- 3.8 mm Hg with 0.7 medications at 1 year. After 1 year, IOP was lower than 21 mm Hg without medication in 36% of patients and lower than 21 mm Hg with medication in 79%. Five patients (9%) required a second operation for pressure control. The following postoperative complications occurred: hyphema (2%); postoperative hypotony less than 10 mm Hg (2%); positive Seidel test (17%); further surgery to lower IOP (12%). Cataract surgery was performed in 1 patient (2%) at 4 months. Despite an attempt to close the scleral flap watertight, 26 patients had evidence of subconjunctival drainage (conjunctival microcysts or filtration bleb) at 1 year. CONCLUSION: Viscocanalostomy lowered IOP and reduced the need for pressure-controlling medications with a low postoperative complication rate. The high success rates of earlier publications were not reproduced.

Anterior Chamber↗

Reactivity and assay restriction profiles of monoclonal and polyclonal antibodies to acid phosphatases: a preliminary study.

The development of secure diagnostic immunoassays requires, among others, rigorous characterisation of potential antibody reagents. The reactivity profiles of seven antibodies (six monoclonal [MAb] and one polyclonal [PAb]) with putative specificity for tartrate-resistant acid phosphatase (TRAP) and/or osteoclasts were evaluated in enzyme-linked immunosorbent assay (ELISA) and/or immunocytochemistry. MAbs 2H1, 4E6 and 5Cl demonstrated assay restriction: exhibiting reactivity only in ELISA. The remaining three MAbs (G211D, G312G and V35B) and the PAb 8023 recognised recombinant TRAP (rTRAP) in ELISA and native acid phosphatases in selected tissues and cell lines. The latter were cytochemically assessed for both tartrate-sensitive acid phosphatase (TSAP) and TRAP. V35B showed reactivity against the monocytic leukaemia cell line U937 and guinea pig kidney tissue (both TSAP+ and TRAP+) and ECV304 (TSAP+) cells. Interestingly, the reactivity of MAb G211D co-localised with TRAP activity in the membrane of osteoclasts but also detected cytoplasmic components in U937 cells and human embryonic lung fibroblasts (TRAP+ and TRAP+). G211D exhibited immunoreactivity against placental trophoblasts (positive for total AP). Intriguingly, MAbs 2H1, 4E6, 5Cl and PAb 8023 cross-reacted with potato acid phosphatase in ELISA, suggesting reactivity to conformationally similar epitopes. Thus, some of these reagents could be used in the development of standardised diagnostic immunoassays or as drug-targeting agents for conditions in which the pathological process involves bone resorption, the MAbs G211D, 2H1, 4E6, 5Cl and PAb 8023 being useful in ELISA but not immunocytochemical detection of TRAP.

Acid Phosphatase↗

[Tectonic epikeratoplasty as an alternative to keratoplasty à chaud?].

PURPOSE: To compare the outcome of epikeratoplasty vs. penetrating keratoplasty in patients with corneal ulcer. PATIENTS AND METHODS: 24 patients had been treated by an epikeratoplasty and 20 patients by a penetrating keratoplasty within 5 years. The indication to operate was progression of a corneal ulcer, perforated ulcer or a descemetocele. In epikeratoplasty a complete cornea with adjacent scleral rim was fixed upon the recipient eye by scleral sutures. This transplant was removed after some weeks. In both groups the patients were reexamined and the anatomical and functional outcome was registered. RESULTS: In both groups all but one globe could be saved. The integrity of corneal surface was restored in 85% (n = 17) of the keratoplasty group and in 75% (n = 18) in epikeratoplasty. The vascularization of the cornea after removing the transplant in epikeratoplasty patients was increased by 70% (n = 17) and their corneas revealed more opacification than before. In the penetrating keratoplasty patient group the vascularization increased in 40% (n = 8) and in 20% (n = 4) of the patients the transplant became cloudy. The visual acuity improved in 13 cases in penetrating keratoplasty but only in two cases after epikeratoplasty. CONCLUSION: A corneal ulcer (with or without perforation) treated by a penetrating keratoplasty with removing the ulcerated tissue has a better outcome than an ulcer covered by an epikeratoplasty. In patients only able to tolerate a short time of surgery with minimal operative risk or if there is no possibility of microsurgical treatment epikeratoplasty may be an alternative to penetrating keratoplasty in saving the globe. However, in most patients penetrating keratoplasty has better functional results.

Adolescent↗

[Significance of forehead and brow lifts].

Forehead and brow lifting, performed alone or in combination with other esthetic surgical procedures, is still a therapeutic aspect of esthetic facial surgery that is little known to both patients and surgeons. However, it is an approach that can be precisely planned and performed, leading to potentially excellent and permanent benefits in the entire frontal and periorbital region. With precise planning and a subtle technique, this is an exceptionally safe approach to permanent correction of age-related conditions throughout the frontal and periorbital region and thus to rejuvenating for many years the focal area of emotionality and overall facial expression.

Adult↗

MK386: a potent, selective inhibitor of the human type 1 5alpha-reductase.

Steroid 5alpha-reductase is required for the conversion of testosterone to dihydrotestosterone. Localization of type 1 5alpha-reductase in the sebaceous gland of skin offers the possibility for selective inhibition of this isozyme as a treatment for acne. The goals of these studies are to demonstrate the mechanism of inhibition of MK386 and its selectivity for type 1 5alpha-reductase. The apparent potency of MK386 differed depending on the source of the enzyme (i.e. recombinant vs. native), yet selectivity for type 1 5alpha-reductase was unchanged. Our results indicate that the apparent potency of MK386 is modulated by the membrane concentration of the assay. These results suggest that MK386 has a high affinity for the lipid-rich membrane environment of 5alpha-reductase. MK386 was also found to be a slow binding inhibitor of type 1 5alpha-reductase. However, the cause of this time-dependent inhibition is unrelated to partitioning of the inhibitor into the membrane because similar studies with type 2 5alpha-reductase indicate that MK386 is a reversible, competitive inhibitor. A number of counterscreens were developed to demonstrate that MK386 is a poor inhibitor of other steroid metabolizing enzymes.

5-alpha Reductase Inhibitors↗

The effect of platelet inhibitory therapy on graft thromboresistance.

Greyhounds (n = 38) were randomized to aspirin and dipyridamole (ASA + DPM), the thromboxane synthetase inhibitor (TSI) CGS12970 (CIBA-GEIGY) or placebo twice daily for 48 hours prior to bilateral implantation of femoral artery Dacron grafts. In-vivo 111In-platelet deposition on grafts was measured at 5 days and 2 months. Grafts were removed at 2 months when ex-vivo graft and arterial release of 6-ketoprostaglandin F1a (6-keto PGF1a) was measured by radioimmunoassay. Graft 6-keto-PGF1a was significantly increased by CGS12970 but ASA + DPM had no significant effect. ASA + DPM significantly reduced arterial 6-keto-PGF1a although this was marginally increased by CGS12970. Neither active treatment reduced in-vivo 111In-platelet deposition. Preservation of vascular or graft prostacyclin by thromboxane synthetase inhibitors may represent an alternative strategy in preventing prosthetic graft thrombosis.

6-Ketoprostaglandin F1 alpha↗

The effect of platelet inhibitory therapy on prosthetic graft maturation.

Thirty-eight dogs were randomized to the thromboxane synthetase inhibitor CGS12790 (3 mg/kg), aspirin 150 mg and dipyridamole 50 mg (ASA + DPM) or placebo (PLA), all twice daily. Two days later, animals underwent bilateral superficial femoral artery replacement with knitted Dacron. Grafts were removed at two months and subjected to macroscopic and histological examination. Thirty dogs survived to two months. Percentage thrombus free area (TFA) was increased from 15.1 +/- 2.2 with PLA to 46.6 +/- 5.2 with CGS12970 (P < 0.001) and to 32.9 +/- 5.0 with ASA + DPM (P < 0.01). At the anastomoses, only CGS12970 significantly reduced neointimal thickness, promoted pannus ingrowth and improved endothelialization. Percentage luminal occlusion at the midgraft was reduced from 48.2 +/- 5.9 with PLA to 33.9 +/- 2.7 with CGS12970 (P < 0.05). These results provide further evidence that platelet inhibitory therapy reduces thrombosis but also that the platelet is involved in anastomotic maturation. Therapy directed against thromboxane synthesis has potential that may be useful in clinical practice.

Animals↗

An immunohistochemical study of mesothelial cell seeding for knitted Dacron.

Six greyhounds underwent bilateral femoral artery replacement with knitted Dacron, one side seeded with omental digest at graft preclotting, the other acting as an unseeded control. Grafts were removed at 24 hours and two months. Tissue was examined using a monoclonal antibody (MNF116) directed against a broad range of human cytokeratins to differentiate mesothelial cells (MC) from microvascular endothelial cells (MEC), which stained only with a polyclonal antibody directed against von Willebrand Factor (anti-vWF). Cells released from omentum by collagenase stained with MNF116 and reacted poorly with anti-vWF. Identical cells were observed to be within the interstices of seeded but not control knitted Dacron. Few remained in seeded grafts (n = 2) removed at 24 hours and none at two months (n = 4).

Animals↗

[Double-guided vacuum trephine system "Asmotom"].

A new, doubly guided cornea suction trephine system is presented. By means of a suction rim placed on the limbus corneal and a suction disc in the centre of the cornea the vault of the cornea is preserved throughout the trephination procedure. Cutting is performed by a motor trephine, which rotates between the inner and the outer suction. The system allows creation of an absolutely safe perforation in a 360 degrees cut. The cut edges are precise and sharp. Both donor and recipient are trephined from the epithelial side. The endothelial cell loss is very low, amounting to 0.170 mm. The suction stabilization prevents any tilting of the trephine and avoids elliptical forms. Preliminary clinical experiences are presented.

Corneal Transplantation↗

Platelet function studies during and after infusions of ZK 36374, a stable prostacyclin analogue, to healthy volunteers.

ZK 36374 (Iloprost), a stable prostacyclin analogue, was administered to 6 healthy volunteers for 2-hour periods, with dose rates increasing from 0.5 to 2 ng/kg/min within that time. At these doses, which did not give troublesome side effects clinically, there was significant inhibition of ex vivo platelet aggregation responses to ADP and collagen. There was some rebound platelet hyperaggregability in all subjects, occurring between 1 and 2 h after termination of the infusion; this was of minor degree and was not associated with any clinical problems.

Adenosine Diphosphate↗

Platelet hyperaggregability occurring during prolonged continuous intravenous infusions of prostacyclin analogue ZK 36374.

We describe two patients suffering from vascular problems refractory to conventional treatment, who received prolonged continuous infusion of ZK 36374, a stable prostacyclin analogue. During the infusion, the patients' platelets became progressively refractory to the in vitro inhibitory action of exogenous ZK 36374. During the early stages of the infusions, platelet aggregability studied ex vivo was inhibited, but this effect too diminished progressively as the infusions continued. The platelets of one patient become spontaneously aggregable and hyperaggregable to standard agonists during the last 2 d of his 9 d infusion. This effect was not seen during an initial 10 d infusion in our second patient, who was concurrently receiving indomethacin, a reversible cyclo-oxygenase inhibitor. However, such hyperaggregability became evident in the platelets of this patient during a second, shorter continuous infusion after cessation of the indomethacin. The hyperaggregability was accompanied in each case by a significant rise in serum thromboxane B2 levels.

Cardiovascular Agents↗

A comparison of the antiviral agents 2'-nor-2'-deoxyguanosine and acyclovir: uptake and phosphorylation in tissue culture and kinetics of in vitro inhibition of viral and cellular DNA polymerases by their respective triphosphates.

A comparative study was conducted between the antiherpetic agents 2'-nor-2'-deoxyguanosine (2'NDG) and acyclovir (ACV) with respect to 1) the relative rates of uptake and phosphorylation to the "active" triphosphate species in tissue culture and 2) the in vitro inhibition of viral and cellular DNA polymerases by their respective triphosphates. The results indicated that a) six hours after HSV1 infection of primary rabbit kidney cells there was seven times more 2'NDG-triphosphate in the cells than ACV triphosphate; b) the relative rate of triphosphate formation in HSV1-infected versus uninfected cells was 4.5 times higher for 2'NDG than for ACV and c) the triphosphate of 2'NDG (2'NDG-TP) was a more selective inhibitor of the viral compared to the cellular DNA alpha-polymerase than the triphosphate of ACV (ACV-TP). The Km/Ki ratios for 2'NDG-TP and ACV-TP (in the competitive inhibition of dGTP) were 3.10 and 1.37, respectively, for the highly purified HSV1 polymerase; and 0.05 and 1.11, respectively, for the partially-purified HeLa alpha-polymerase. Neither triphosphate inhibited the HeLa DNA beta-polymerase to any significant extent. These results are in line with the findings [Ashton et al. (1982), Biochem. Biophys. Res. Commun. 108, 1716-1721] that 2'NDG has superior in vivo antiherpetic activity compared to ACV without apparent toxicity.

Acyclovir↗

Evidence for a platelet membrane defect in the myeloproliferative syndromes.

Bleeding and abnormal platelet aggregation occur in patients with myeloproliferative disorders. In this study, twenty patients were examined, some sequentially, and a proportion found to have defective aggregation toward adrenaline, adenosine diphosphate (ADP), and collagen. In these seven patients, the abnormality in platelet response with defective collagen-induced [14C]serotonin release correlated with poor collagen-stimulated thromboxane B2 (TXB2) production. In contrast, five of these patients showed a normal threshold aggregation response to arachidonic acid. The combined results suggest that in these patients, there is a defect between receptor-stimulus coupling and the mobilization of arachidonic acid from membrane phospholipid.

Blood Platelets↗