Andrew C. Hall

A randomized controlled trial comparing mebendazole and albendazole against Ascaris, Trichuris and hookworm infections

The efficacies and side effects of single dose treatments with 500 mg mebendazole (Janssen Pharmaceutica) and 400 mg albendazole (SmithKline Beecham) against intestinal nematodes were compared in a single-blind, randomized controlled trial among 2294 children aged 6 to 12 years on Pemba Island, Zanzibar, among whom infections with Ascaris, hookworms and Trichuris were highly prevalent. Both drugs were highly effective against Ascaris, with cure rates of over 97%. The cure rates for Trichuris were low, but mebendazole was significantly better than albendazole and produced a greater reduction in the geometric mean egg count. Mebendazole was inferior to albendazole in curing hookworm infections and in reducing the geometric mean egg count. There was no difference in the frequency of side effects reported by heavily infected children treated with either drug. In a trial on 402 children, 500 mg mebendazole (Janssen) was compared with a generic version of the drug, 500 mg mebendazole (Pharmamed). No difference was apparent in the efficacies of the 2 treatments against any of the 3 parasites studied.

Chondrocyte death associated with human femoral osteochondral harvest as performed for mosaicplasty

BACKGROUND Autologous osteochondral transfer is an option for the treatment of articular defects. However, there are concerns about graft integration and the nature of the tissue forming the cartilage-cartilage bridge. Chondrocyte viability at graft and recipient edges is thought to be an important determinant of the quality of repair. The purpose of the present study was to evaluate early cell viability at the edges of osteochondral grafts from ex vivo human femoral condyles. METHODS Fresh human tissue was obtained from eleven knees at the time of total knee arthroplasty for the treatment of osteoarthritis. Osteochondral cylinders were harvested with use of a 4.5-mm-diameter mosaicplasty osteotome from regions of the anterolateral aspect of the femoral condyle that were macroscopically nondegenerate and histologically nonfibrillated. Plugs were assessed for marginal cell viability by means of confocal laser scanning microscopy. RESULTS The diameter of the cartilaginous portion of the osteochondral plugs was a mean (and standard error of the mean) of 4.84 +/- 0.12 mm (as determined on the basis of three plugs). This value was approximately 300 microm greater than the measured internal diameter of the osteotome. There was a substantial margin of superficial zone cell death (mean thickness, 382 +/- 68.2 microm), with >99% cell viability seen more centrally (as determined on the basis of five plugs). Demiplugs were created by splitting the mosaicplasty explants with a fresh number-11 scalpel blade. The margin of superficial zone cell death at the curved edge was significantly greater than that at the site of the scalpel cut (390.3 +/- 18.8 microm compared with 34.8 +/- 3.2 microm; p = 0.0286). Similar findings were observed when the cartilage alone was breached and the bone was left intact, with the margin of superficial zone cell death being significantly greater than that obtained in association with the straight scalpel incision (268 +/- 38.9 microm compared with 41.3 +/- 13.4 microm; p = 0.0286). The margin of superficial zone cell death showed no increase during the time-period between fifteen minutes and two hours after plug harvest. A mathematical approximation of the mosaicplasty region suggested that early cell death of this magnitude affects about one third of the superficial graft area. CONCLUSIONS The results of the present study suggest that mosaicplasty, while capable of transposing viable hyaline cartilage, is associated with an extensive margin of cell death that is likely to compromise lateral integration and articular reconstruction.

The volume and morphology of chondrocytes within non-degenerate and degenerate human articular cartilage

OBJECTIVE Cartilage swelling is an early event in osteoarthritis (OA). However, the response of chondrocytes to increased tissue hydration is unknown. This work studied the volume and morphology of living in situ human chondrocytes as a function of cartilage degeneration. METHODS The tibial plateaus from knee joints of 40 patients were obtained following above-knee amputations or knee arthroplasty, and degree of cartilage degeneration from 0 (non-eroded) to 3 (extensive fibrillations) was assessed using several criteria. In situ chondrocytes were labeled with fluorescent indicators (calcein for living cells, propidium iodide for dead cells) permitting the quantification of volume and visualisation of morphology of cells within the cartilage zones by confocal scanning laser microscopy (CLSM). RESULTS Chondrocyte volume within superficial and mid-zones, but not of deep zone cells, increased significantly (P<0.05 and P<0.02, respectively; one-way analysis of variance), with degree of cartilage hydration and degeneration. The volume increase ( approximately 90% for mid-zone chondrocytes, grade 3 cartilage) was greater than that which might occur following loss/excision of sub-chondral bone (<15% swelling). The CLSM technique utilised here revealed that approximately 40% of chondrocytes within all cartilage grades exhibited at least one cytoplasmic processes of <8 microm. The presence of these processes did not indicate a cell body of larger volume than cells without processes, and did not contribute to cell volume. CONCLUSIONS The volume of in situ chondrocytes within the superficial and mid-zones increased with cartilage degeneration. Cell swelling was greater than that expected from the increased hydration in OA, suggesting that an increase in chondrocyte volume might play a role in the changes to matrix metabolism occurring in OA.

Regulatory volume decrease (RVD) by isolated and in situ bovine articular chondrocytes

Articular chondrocytes in vivo are exposed to a changing osmotic environment under both physiological (static load) and pathological (osteoarthritis) conditions. Such changes to matrix hydration could alter cell volume in situ and influence matrix metabolism. However the ability of chondrocytes to regulate their volume in the face of osmotic perturbations have not been studied in detail. We have investigated the regulatory volume decrease (RVD) capacity of bovine articular chondrocytes within, and isolated from the matrix, before and following acute hypotonic challenge. Cell volumes were determined by visualising fluorescently‐labelled chondrocytes using confocal laser scanning microscopy (CLSM) at 21°C. Chondrocytes in situ were grouped into superficial (SZ), mid (MZ), and deep zones (DZ). When exposed to 180mOsm or 250mOsm hypotonic challenge, cells in situ swelled rapidly (within ∼90 sec). Chondrocytes then exhibited rapid RVD (t1/2 ∼ 8 min), with cells from all zones returning to ∼3% of their initial volume after 20 min. There was no significant difference in the rates of RVD between chondrocytes in the three zones. Similarly, no difference in the rate of RVD was observed for an osmotic shock from 280 to 250 or 180mOsm. Chondrocytes isolated from the matrix into medium of 380mOsm and then exposed to 280mOsm showed an identical RVD response to that of in situ cells. The RVD response of in situ cells was inhibited by REV 5901. The results suggested that the signalling pathways involved in RVD remained intact after chondrocyte isolation from cartilage and thus it was likely that there was no role for cell‐matrix interactions in mediating RVD.

Epidemiology of soil-transmitted nematode infections in Ha Nam Province, Vietnam

Baseline epidemiological data are presented from a parasitological survey conducted in Thuy Loi commune, Ha Nam province, Vietnam; a farming community where night soil is routinely used as fertilizer for crops. 177 households were visited and 543 individuals (aged 1–88 years) recruited to the study. Helminth infection intensity was assessed by Kato‐Katz to determine the density of parasite eggs per gram of stool (epg). Ascaris lumbricoides, Trichuris trichiura and hookworm infections were the only species detected. 83% of individuals were infected with A. lumbricoides (mean epg = 11971), 94% with T. trichiura (mean epg = 793) and 59% with hookworm (mean epg = 302). Age‐dependent patterns of infection prevalence and intensity were similar for A. lumbricoides and T. trichiura, but markedly different for hookworm infection. Similarly, age‐dependency in the k‐values for the three infections was due to covariance with the respective mean intensities with age rather than to independent age effects, with similar patterns for A. lumbricoides and T. trichiura, and a different pattern for hookworm. Three major conclusions can be drawn from the multiple‐species analyses: There is positive interaction between A. lumbricoides and T. trichiura infections; high‐intensity A. lumbricoides infections are significantly associated with high‐intensity T. trichiura infections; and there is positive interaction between these two species such that infection intensity of A. lumbricoides is higher in individuals with concurrent T. trichiura infection than in individuals without and vice versa.

School Enrolment Patterns in Rural Ghana: A Comparative Study of the Impact of Location, Gender, Age and Health on Children's Access to Basic Schooling.

The aim of this article is to discuss the results from three censuses conducted on school age children in rural Ghana which reveal contemporary patterns in enrolment. The data provide a profile of the school age population in basic education and contribute novel quantitative data on children out of school. The article examines the age at first enrolment, the gender disparities between classes, the classes where children drop out, and the proportion of children who never enrol in school. The stark contrast in enrolment between the disadvantaged north and the south of the country is also confirmed. Qualitative data from focus group discussions with parents, teachers and children highlight the major obstacles confronting education-these include a diversity of factors such as child labour, health, location and gender. Suggestions of policy options needed to increase access and attainment to schooling include reducing the over-age entry, increasing female access and participation, adapting culturally sensitive...

The impact of population level deworming on the haemoglobin levels of schoolchildren in Tanga,Tanzania

Summary The impact of albendazole (400 mg) and praziquantel (40 mg/kg body weight) treatment of schoolchildren was compared with placebo according to the presence of anaemia (haemoglobin concentration < 11.0 g/dl) and heavy (> 5000 epg) or light (< 5000 epg) hookworm egg load. The study was conducted in rural Tanga. Medication was administered in September 1994 and children were followed‐up in January 1995. Overall, anthelminthic treatment reduced the fall in haemoglobin concentration compared with that observed in the placebo group (− 0.11 g/dl vs. − 0.35 g/dl; P = 0.02). Anthelminthic treatment was of greatest benefit to the 9% of children with both anaemia and heavy hookworm egg load (+ 0.67 g/dl vs. − 0.67 g/dl) and was also of significant benefit to the 38% of children with anaemia and light hookworm egg load (+ 0.07 g/dl vs. − 0.21 g/dl). It was of no significant benefit to children who were not anaemic. This study suggests that single‐dose anthelminthic treatment distributed in schools in this area achieves haematological benefits in nearly half of children infected with S. haematobium and geohelminths (37% of total population).

Volume-sensitive taurine transport in bovine articular chondrocytes.

1. The swelling of bovine articular chondrocytes isolated from, or in situ within, cartilage by hypotonic shock rapidly activated the efflux or influx of radiolabelled taurine, an amino acid involved in volume regulation in a range of other cell types. 2. When chondrocytes were isolated by the use of collagenase into media of 280 or 380 mosmol l‐1, the activation of taurine efflux was at about the osmolarity of the isolating medium, but it was more marked for a given hypotonic shock in the cells isolated at the lower osmolarity. The volume of chondrocytes following isolation in these two osmolarities was the same, suggesting that the cells possess volume regulatory capacity. 3. In isolated chondrocytes, the induced pathway had some of the characteristics of a volume‐activated channel, i.e. no transport saturation with increasing substrate concentration, and lack of trans acceleration. The pattern of inhibition of the volume‐activated pathway by pharmacological blockers (e.g. pimozide, [(dihydro‐indenyl)oxy]alkanoic acid (DIOA) and tamoxifen) differed from that described for a similar pathway in other cell types. 4. The transport of other potential osmolytes (uridine, sorbitol and inositol) was stimulated by cell swelling, independent of sodium and inhibited by pimozide with a selectivity ratio of taurine, 1.00; uridine, 0.84; sorbitol, 0.66; and inositol, 0.38. The selectivity of taurine: inositol was not altered at different cell volumes. 5. The intracellular taurine concentration of chondrocytes within cartilage was low (about 2 mmol (l cell water)‐1) showing a negligible role for taurine as an osmolyte during recovery from cell swelling. The swelling‐induced loss of taurine from chondrocytes in situ was largely inhibited by pimozide and other drugs, showing that despite the rigid nature of cartilage, the chondrocytes were osmotically sensitive within the extracellular matrix.

Differential effects of hydrostatic pressure on cation transport pathways of isolated articular chondrocytes

Articular cartilages are exposed to significant loads in vivo, which by their effects on chondrocyte metabolism can alter the mechanical properties of the extracellular matrix. The mechanism(s) by which chondrocytes sense and respond to load are not well understood. One component of load, hydrostatic pressure, can be studied independently of the other factors that change during load. In this study, the effects of pressure have been investigated on three K transport pathways in isolated bovine articular chondrocytes. Pressure inhibited the Na/K pump (ouabain‐sensitive), Na/K/2Cl cotransporter (bumetanide‐sensitive), and residual (ouabain‐ and bumetanide‐insensitive) pathways; however, the response of each system was different. Both pressure level and duration were important in determining the extent of inhibition. There was marked suppression of the Na/K pump, particularly when pressure (2.5–50 MPa) was maintained for the full incubation period (usually 10 min). The Na/K/2Cl cotransporter was more pressure‐sensitive, with only a short application (20 sec) of a low pressure (7.5 MPa) being sufficient for inhibition. Over the higher range (20–50 MPa), pressure had little further effect. The inhibitory action on the Na/K pump was dependent on the [Na]i. Thus, when the [Na]i was set to values above or below those normally present, the inhibitory effect was reduced or abolished. The suppressive effect of pressure on Na/K pump and residual pathways was reversed at atmospheric pressure. The pressure dependence of inhibition of the K flux through the residual pathway was similar to that reported for lipid bilayers. These results indicate that hydrostatic pressure may act directly on chondrocyte membrane transporters. Alterations to matrix synthesis resulting from the application of load might therefore result in part from variations to the intracellular ionic/osmotic composition of chondrocytes arising from changes to the activity of membrane transport pathways. J Cell Physiol 178:197–204, 1999.

Osmolarity influences chondrocyte death in wounded articular cartilage

BACKGROUND Mechanical injury results in chondrocyte death in articular cartilage. The purpose of the present study was to determine whether medium osmolarity affects chondrocyte death in injured articular cartilage. METHODS Osteochondral explants (n = 48) that had been harvested from the metacarpophalangeal joints of three-year-old cows were exposed to media with varying osmolarity (0 to 480 mOsm) for ninety seconds to allow in situ chondrocytes to respond to the altered osmotic environment. Explants were then wounded with a scalpel through the full thickness of articular cartilage, incubated in the same media for 2.5 hours, and transferred to 340-mOsm Dulbeccos Modified Eagle Medium (control medium) with further incubation for seven days. The spatial distribution of in situ chondrocyte death, percentage cell death, and marginal cell death at the wounded cartilage edge were compared as a function of osmolarity and time (2.5 hours compared with seven days) with use of confocal laser scanning microscopy. RESULTS In situ chondrocyte death was mainly localized to the superficial tangential zone of injured articular cartilage for the range of medium osmolarities (0 to 480 mOsm) at 2.5 hours and seven days. Therefore, a sample of articular cartilage from the superficial region (which included the scalpel-wounded cartilage edge) was studied with use of confocal laser scanning microscopy to compare the effects of osmolarity on percentage and marginal cell death in the superficial tangential zone. Compared with the control explants exposed to 340-mOsm Dulbeccos Modified Eagle Medium, percentage cell death in the superficial tangential zone was greatest for explants exposed to 0-mOsm (distilled water) and least for explants exposed to 480-mOsm Dulbeccos Modified Eagle Medium at 2.5 hours (13.0% at 340 mOsm [control], 35.5% at 0 mOsm, and 4.3% at 480 mOsm; p <or= 0.02 for paired comparisons) and seven days (9.9% at 340 mOsm [control], 37.7% at 0 mOsm, and 3.5% at 480 mOsm; p <or= 0.01 for paired comparisons). Marginal cell death in the superficial tangential zone decreased with increasing medium osmolarity at 2.5 hours (p = 0.001) and seven days (p = 0.002). There was no significant change in percentage cell death from 2.5 hours to seven days for explants initially exposed to any of the medium osmolarities. CONCLUSIONS Medium osmolarity significantly affects chondrocyte death in wounded articular cartilage. The greatest chondrocyte death occurs at 0 mOsm. Conversely, increased medium osmolarity (480 mOsm) is chondroprotective. The majority of cell death occurs within 2.5 hours, with no significant increase over seven days.