Mesenchymal Stromal Cells Protect Endothelial Cells from Cytotoxic T Lymphocyte-Induced Lysis.

The integrity of the vasculature plays an important role in the success of allogeneic organ and haematopoietic stem cell transplantation. Endothelial cells (EC) have previously been shown to be the target of activated cytotoxic T lymphocytes (CTL) resulting in extensive cell lysis. Mesenchymal stromal cells (MSC) are multipotent cells which can be isolated from multiple sites, each demonstrating immunomodulatory capabilities. They are explored herein for their potential to protect EC from CTL-targeted lysis. CD8(+) T cells isolated from human PBMC were stimulated with mitotically inactive cells of a human microvascular endothelial cell line (CDC/EU.HMEC-1, further referred to as HMEC) for 7 days. Target HMEC were cultured in the presence or absence of MSC for 24 h before exposure to activated allogeneic CTL for 4 h. EC were then analysed for cytotoxic lysis by flow cytometry. Culture of HMEC with MSC in the efferent immune phase (24 h before the assay) led to a decrease in HMEC lysis. This lysis was determined to be MHC Class I restricted linked and further analysis suggested that MSC contact is important in abrogation of lysis, as protection is reduced where MSC are separated in transwell experiments. The efficacy of multiple sources of MSC was also confirmed, and the collaborative effect of MSC and the endothelium protective drug defibrotide were determined, with defibrotide enhancing the protection provided by MSC. These results support the use of MSC as an adjuvant cellular therapeutic in transplant medicine, alone or in conjunction with EC protective agents such as defibrotide.

The value of HAZWOPER medical surveillance.

Medical surveillance is mandated for workers with potential exposure to hazardous materials. However, little guidance is provided regarding the components of a medical surveillance testing program for these individuals. This article describes the medical surveillance program for a group of 72 employees who respond to hazardous material releases throughout the United States. Conditions related to chemical exposures were not identified in this group. However, several non-occupational health conditions were identified, including a relatively high prevalence of one or more signs of metabolic syndrome. Medical surveillance may provide valuable information regarding an individual's underlying health status and non-occupational health conditions to be addressed at an early stage.

[Cell-based strategies for salivary gland regeneration]. / Zellbasierte Strategien für die Speicheldrüsenregeneration.

Xerostomia as a side effect of radiotherapy or due to Sjögren's disease leads to considerable impairment of the quality of life of the affected patients. Preventive treatment approaches such as intensity-modulated radiotherapy, surgical transfer of a submandibular gland to a site outside the radiation field or administration of amifostin during radiation treatment are not yet completely established in clinical practice and are not applicable for all patients. Symptomatic treatment with pilocarpin or synthetic saliva leads to an improvement of the symptoms only in some patients, and in the case of pilocarpin significant systemic anticholinergic side-effects might occur. Because large numbers of patients are affected and current treatment options are not satisfactory, it is essential to develop new treatment options. In parallel with the in vitro production of functional salivary gland constructs by means of tissue engineering techniques, attempts are currently under way to experimentally restore salivary gland function by genetic treatment approaches such as transfection of the affected salivary glands with aquaporins or pro-angiogenic factors. In addition, the in vivo application of stem cells is under investigation. In the present paper, we discuss the clinical and radiobiological background of xerostomia and highlight possible innovative future treatment options.

Natural history and surgical treatment of brown tumor lesions at various sites in refractory primary hyperparathyroidism.

OBJECTIVE: Nowadays, the occurrence of brown tumor lesions or osteitis fibrosa cystica caused by long-lasting primary hyperparathyroidism are very rare, since measuring serum calcium became available routinely in the mid-1970s. It is a tumor-like lesion that may affect the entire skeleton, often presenting with diffuse focal bone pain or by pathological fracture. METHODS: We describe our experience of brown tumor lesions at different skeletal sites that were treated at our trauma centre within the last two years. This included surgical therapy for the indications (i) pain at the pelvis, (ii) increased risk for pathological fracture at the tibia and (iii) acute radicular symptoms at the lumbar spine. The literature was reviewed for the current understanding of the pathophysiology as well as therapy of brown tumor lesions in primary hyperparathyroidism. RESULTS: Curettage of a left-sided iliac crest brown tumor terminated focal pain. A less invasive stabilisation system and bone cement decreased both patient pain and the fracture risk of brown tumor lesion sites of the shinbone; and internal fixator including laminectomy at the lumbar spine ended radicular symptoms. CONCLUSION: Patients with refractory primary hyperparathyroidism should be monitored closely by endocrinologists and the patient's serum calcium level should be adjusted as far as possible. Radiography is required only if focal bone pain or pathological fractures or radicular symptoms occur. Surgery should be considered if large bone defects with spontaneous fracture risk or increasing pain are present. Tumor curettage, Palacos plombage and less invasive stabilisation systems have proved to be acceptable surgical options.

Ultrastructural localization of stem cell factor in canine marrow-derived stromal cells.

Stromal cell lines derived from canine long-term bone marrow cultures (LTBMC) were characterized regarding the expression of growth factors and especially the localization of stem cell factor (SCF) (c-kit ligand). One cell line (DO64) was immortalized by transformation with a retroviral vector containing the open reading frames (ORFs) E6 and E7 of the human papilloma virus type 16 (HPV-16). Transfection did not change cellular characteristics but rendered the cell line more independent from culture conditions. The transformed line DO64 consisted mainly of fibroblast-like cells. In addition, some cells showed endothelial and some smooth-muscle cell features. Stromal cells expressed a broad spectrum of surface markers, including low levels of major histocompatibility-complex (MHC) class-II antigens. A new murine monoclonal antibody (MAb), RG7.6 (IgG1), specific for canine SCF, recognized the majority of fibroblast-like stromal cells. The staining pattern for SCF showed perinuclear and intracytoplasmic dense areas. Immunoelectron microscopy revealed the localization of SCF in secretory vesicles, the perivesicular cytoplasm, and bound to the cytoplasmatic membrane. RNA analysis showed that stromal cells transcribed, in addition to SCF, messages for granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte CSF (GM-CSF), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta). In summary, we have established and characterized canine marrow-derived stromal cell lines, and using the new MAb RG7.6, we have localized SCF to cytoplasmatic vesicles as well as the membrane of stromal cells.

Major histocompatibility complex class II expression is required for posttransplant immunological but not hemopoietic reconstitution in mice.

We had previously shown in a canine model that the administration of anti-MHC class II monoclonal antibody (MAB) immediately after autologous marrow transplantation prevented hemopoietic reconstitution. Since MHC class II expression in mice differs from that in dogs we were interested in determining the effect of MHC class II manipulation on posttransplant hemopoietic and immunological recovery in mice. Three murine models including MHC class II knock-out mice were studied. BALB/c mice (I-E+, I-A+) given anti-MHC class II MAB H81.9 (anti-I-E; 1 mg/kg/day, days 0-4) after TBI and infusion of syngeneic marrow or infused with anti-I-E purged marrow both showed normal hemopoietic reconstitution. Similarly, C57B1/6 mice (I-E-, I-A+) transplanted with M5/114 (anti-I-A) purged marrow recovered normal hemopoiesis. MHC class II knock-out (C2D) mice, which lack class II completely, also recovered normal hemopoiesis after TBI and transplantation with either normal or class II-deficient (C2D) marrow, although the kinetics of platelet recovery as determined by megakaryocytopoiesis and platelet counts on day 14 were slightly delayed. C57B1/6 mice transplanted with C2D marrow recovered normally. Immunologic recovery, however, was abnormal both in C2D recipients and in normal mice transplanted with C2D marrow: While CD8+ T lymphocytes recovered normally, no (or only very few) CD4+ T cells were identified posttransplant. Treatment of normal mice with anti-MHC class II MAB in vivo or transplantation of MHC class II-purged marrow, however, did not interfere with complete immunological recovery, although T cell maturation was slightly delayed. Thus, complete immunological reconstitution requires the expression of MHC class II on marrow-derived precursor cells, while the expression of MHC class II antigens is not a requirement for hemopoietic reconstitution in mice.

Major histocompatibility complex class II molecules, hemopoiesis and the marrow microenvironment.

Currently available data indicate that the earliest identifiable hemopoietic progenitor in normal marrow is CD34+ MHC class II-; subsequent expression of MHC class II antigens is maturation and lineage dependent. Studies on embryonal cells suggest that CD34+DR- cells are actually the common precursors for stromal and hemopoietic elements, with the earliest hemopoietic precursor being CD34+DR+. DQ antigens are apparently not expressed in cells of hemopoietic potential and the expression of DQ appears to be regulated differentially from DR and DP. MHC class II antigens are also expressed on some stromal cells, especially those with endothelial and macrophage features. MHC class II molecules are involved in hemopoietic cell/stroma interaction. The presence of anti-MHC class II monoclonal antibodies (MABs) at early stages of stem cell proliferation/differentiation, at least under conditions of marrow stress, induces signals which may result in final, especially granulocytic, differentiation of later precursors. These may interfere with the survival of those cells which are required for long-term hemopoietic reconstitution. Observations in allogeneic marrow transplant recipients support a role of MHC molecules as expected in allogeneic interactions. Results in autologous models point towards a role of MHC class II molecules other than that of a histocompatibility marker insofar as these molecules or signals transmitted by them appear to be involved in the regulation of hemopoiesis.

Effect of mixed chimerism on graft-versus-host disease, disease recurrence and survival after HLA-identical marrow transplantation for aplastic anemia or chronic myelogenous leukemia.

The association of mixed (donor/host) chimerism with graft-versus-host disease (GVHD), graft rejection, disease recurrence and survival was investigated in 116 patients with aplastic anemia and 197 patients with chronic myelogenous leukemia (CML) transplanted with unmodified marrow from an HLA-identical sibling donor of opposite sex. Patients with aplastic anemia were conditioned with cyclophosphamide (CY), patients with CML were conditioned with a combination of CY and total body irradiation (TBI) or busulfan. Sixty-three of the patients with aplastic anemia (54%) and 100 patients with CML (51%) were categorized as mixed chimeras based on the concurrent presence of donor and host lymphohematopoietic cells 14 days or later after transplantation. The TBI dose used for conditioning was inversely correlated with the development of mixed chimerism (P < 0.0001) among CML patients. No other patient- or transplant-related parameter was identified which contributed significantly to the development of mixed chimerism. The incidence of rejection was higher but not significantly so in patients with aplastic anemia who were mixed chimeras. The incidence of leukemic relapse in patients with CML who were mixed chimeras was increased only if mixed chimerism occurred after day 100 (P = 0.015). The incidence of acute GVHD (grades II-IV) was lower in mixed chimeras than in complete chimeras, but this difference was statistically significant only for patients with aplastic anemia given single-agent GVHD prophylaxis (P = 0.0008). Mixed chimeras in that group also had a better survival than complete chimeras, while no significant difference was observed in patients with aplastic anemia given drug combinations for GVHD prophylaxis. Among patients with CML, both overall survival (P = 0.03) and relapse-free survival (P = 0.04) were significantly superior in mixed than in complete chimeras. Thus, mixed chimerism was frequent among patients with aplastic anemia and with CML and was not uniformly associated with graft failure or leukemic relapse. The interaction between conditioning regimen, GVHD prophylaxis and chimerism are complex. The survival advantage of mixed chimeras is only in part related to a lower incidence of GVHD and other factors are likely to contribute.

Tacrolimus (FK506) and methotrexate regimens to prevent graft-versus-host disease after unrelated dog leukocyte antigen (DLA) nonidentical marrow transplantation.

We previously reported an synergism between methotrexate and tacrolimus (FK506) in preventing graft-versus-host disease (GVHD) in dogs given DLA-nonidentical unrelated marrow grafts after 9.2 Gy of total body irradiation (TBI). Methotrexate was given at 0.4 mg/kg i.v. on days 1, 3, 6 and 11 and FK506 at 0.15 mg/kg/day i.m. on days 0-8 and 0.5 mg/kg/day orally on days 9-90. Half of the dogs became long-term survivors. A major toxicity was gastrointestinal, and 25% of dogs died with intussusception. The current study addresses the problem of intussusception by making changes in drug doses used. In one group of dogs, FK506 was reduced to 0.075 mg/kg i.m. on days 1-8, while methotrexate was administered per original schedule. In a second group, methotrexate was reduced to a single dose on day 7, while FK506 was either administered per the original or reduced-dose schedule. None of the 17 current dogs developed intussusception, however, all but two dogs died with GVHD (n = 12) or graft failure (n = 3). Only two dogs survived after transient GVHD. Results show that there is little room for maneuvering FK506 or methotrexate doses, and hopes of reducing gastrointestinal toxicity by dose modifications while retaining the ability to prevent GVHD were not fulfilled.

Impairment of genomic DNA binding to a putative dysfunctional receptor on erythrocytes independent of complement and antibodies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by a variety of autoantibodies and other immune abnormalities indicative of an immunological hyperactivity. Antibodies against native DNA, however, are a disease-specific marker and play a major role in the pathogenesis of systemic or organ-specific disease manifestations. Nevertheless, the mechanisms causing the appearance of autoantibodies and immune complexes in SLE are not yet understood. Here, we report that chromosomal DNA and other forms of nucleic acids are usually cleared from circulation by binding to a yet unidentified receptor-like protein on the surface membrane of erythrocytes, independently from complement or antibodies. The binding kinetics of DNA and other nucleic acids to erythrocytes are significantly altered in SLE patients, showing an overall reduced binding capability and presaturated binding kinetics. Significant amounts of chromosomal DNA can be isolated from erythrocytes of SLE patients but not from normal controls. Electron microscopy shows electron-dense particles on the surface of SLE erythrocytes (approximate size 20-40 nm). Comparative genomic hybridization reveals that the nucleic acid isolated from erythrocytes of SLE patients is of genomic and random origin, leading to an accumulation of "free" nucleic acids in the periphery, which eventually induces a B-cell immune response.

In vitro determination of self-reactivity in the early postcyclosporine period.

Since cyclosporine A(CsA) was introduced into transplantation medicine to prevent graft-versus-host disease (GvHD) as well as graft rejection, side-effects became obvious. When CsA is given and withdrawn GvHD-like symptoms can occur even in an autologous setting. To understand this mechanism we tested the allo- and self-reactivity of murine spleen lymphocytes in an in vitro assay. Mice of four different strains with two distinct MHC class I backgrounds (H-2d and H-2k) were treated with 60 mg/kg/day CsA intraperiteonally for ten days. In an attempt to examine the possibility that the CsA-induced autoimmunity requires the presence of the thymus, half of these four- to six-week-old mice were also thymectomized prior to the CsA treatment. Within one day after CsA was stopped, all mice that received CsA during treatment showed reactivity against self-MHC-bearing spleen cells. This was demonstrated in a primary in vitro stimulation assay followed by a chromium-release assay (H-2d-anti-H-2d and H-2k-anti-H-2k). However, alloreactivity (H-2d-anti-H-2k and H-2k-anti-H-2d) was suppressed. At this point in time, no natural killer (NK) activity was detectable in any of the CsA-treated mice. Ten days after stopping CsA, the autoreactivity was no longer detectable in any mouse strain, whether thymectomized or not, whereas the alloreactivity and the NK activity finally recovered. The in vitro phenomena of self-reactivity, which occurred between day one and day 10 after CsA withdrawal, could be adoptively transferred from syngeneic in vitro reactive T cell populations into H-2 identical mice. (ABSTRACT TRUNCATED AT 250 WORDS)

Facilitation of DLA-incompatible marrow grafts by donor-specific serum transferrin?

Studies in mice have shown that donor-specific plasma transferrin (TF) given to the recipient in the peritransplant period facilitates engraftment of marrow from histoincompatible donors. Dogs given 920 cGy of total body irradiation (TBI) and infused with marrow from an unrelated major histocompatibility complex (DLA) different donor generally fail to engraft; only approximately 20% of dogs achieve sustained engraftment. We have now investigated in this model whether the infusion of donor-specific plasma TF would facilitate engraftment. Ten dogs were given TBI, followed at 23 h by an intravenous dose of TF, at 24 h by marrow from the same donor, and another dose of TF at 48 h; six dogs also received postgrafting methotrexate (MTX). Seven dogs (three of four without MTX, four of six with MTX) had sustained engraftment, and three dogs failed to engraft. A single dog given third-party TF failed to engraft. Among five dogs not given TF two achieved sustained engraftment. This pilot study suggests that donor-specific TF facilitates engraftment of DLA-incompatible marrow. Further studies are warranted.

Homing and immunogenicity of murine stromal cells transfected with xenogeneic MHC class II genes.

Syngeneic (murine) and xenogeneic (canine) marrow-derived stromal cells were injected intravenously into SCID and normal mice to examine the homing pattern and persistence of these cells in vivo. By in situ hybridization, these stromal cells were detectable in the bone marrow cavity and the spleen 21 days after injection. Xenogeneic cells did not persist in normal mice but persisted in SCID mice. Conditioning of the recipients with irradiation or 5-fluorouracil (5-FU) treatment did not alter these results. In addition, syngeneic murine stromal cells were transfected with the genes for canine MHC class II (DRA + DRB) and transplanted into murine recipients to investigate their homing pattern and immunogenicity. These transfected syngeneic stromal cells did also home to marrow and spleen even in normal recipients. However, these cells led to sensitization of the host towards canine antigens as shown by accelerated skin graft rejection and delayed type hypersensitivity (DTH). Thus, immunodeficient (SCID) mice allow for the homing of xenogeneic stromal cells to hemopoietic organs and for prolonged persistence. In immunocompetent (normal) mice, no xenogeneic stromal cells were identified in spleen and marrow, either because of their inability to home or more likely because of immunological rejection. In contrast, syngeneic stromal cells expressing xenogeneic MHC class II genes did home to spleen and marrow and persisted even though the recipient had become sensitized. Their survival may be due to a loss of expression of the transfected gene. Alternatively, the presentation of these xenogeneic gene products in the hemopoietic organs was such that a cytotoxic response was not induced.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine-induced diuresis in the cat without changes in renal hemodynamics.

The effects of intravenous (i.v.) and intraarterial (i.a.) injection and infusion of dopamine (DA) on renal hemodynamics, regional sympathetic activity and kidney function were investigated in anaesthetized cats. In response to the i.v. bolus injection of DA (25 microgram/kg), mean arterial blood pressure (MABP) was increased by 19.7%, renal blood flow (RBF) by 16.6%, and regional sympathetic discharges were inhibited. The principal effect of i.a. bolus injection of DA into the renal artery was vasoconstriction. Vasodilation was observed neither after lower doses of DA nor after pretreatment with phenoxybenzamine. During continuous i.v. infusion of 10 microgram DA kg-1 min-1 MABP, RBF, renal sympathetic discharges and glomerular filtration rate (GFR) did not change, whereas urine volume was increased by 120.5%, sodium excretion by 99.7%, chloride excretion by 143.2%, and potassium excretion by 31.9%. Urine osmolality was decreased and osmolal clearance increased. Raising the DA dose to 25 microgram kg-1 min-1 resulted in a fall of GFR, but the diuretic response was not significantly different from that of the low dose. Bulbocapnine (6 mg/kg i.v.) antagonized the DA-induced diuresis. In conclusion, the diuretic effect of DA in the cat is not dependent on a change in RBF, GFR or renal sympathetic activity. This suggests that a tubular site of action is primarily responsible for DA diuresis.

Blindness and visual impairment in a region endemic for onchocerciasis in the Central African Republic.

AIMS: A population based survey of blindness and visual impairment was conducted in the district of Bossangoa, Central African Republic. METHODS: A total of 48 communities were randomly selected, and 6086 people examined. RESULTS: The prevalence of blindness (visual acuity in the better eye less than 3/60) was 2.2%, and visual impairment 3.0% (6/24 to 3/60 in the better eye). The major causes of blindness were onchocerciasis (73.1%), cataract (16.4%), trachoma (4.5%), and glaucoma (2.2%). CONCLUSION: Around 95.5% of all blindness could potentially have been prevented or treated. Ivermectin mass distribution is hoped to prevent 50% of all forms of visual loss in the future.

Functional and ultrastructural studies on the burst of c-kit ligand containing secretory cytoplasmatic vesicles.

A fibroblast-like cell line (D064) was established from canine marrow long-term cultures. These cells start to differentiate into hematopoietic progenitor precursors under the influence of c-kit ligand, functioning in an autocrine and paracrine fashion. The message for c-kit ligand is transcribed in the fibroblast-like cell line and the ligand for the tyrosine-kinase c-kit is expressed on the cell surface as well as secreted in its soluble form. With a monoclonal antibody directed against all isoforms of c-kit ligand, the expression of c-kit ligand was investigated functionally and topographically by electron microscopy. Ultrastructural analysis revealed c-kit ligand in electron dense vesicles which were transported to the cell surface and burst to release the soluble, non-membrane bound isoform of c-kit ligand. A membrane bound isoform of c-kit ligand was also present on the cell membrane.

A mathematical model of forces in the knee under isometric quadriceps contractions.

OBJECTIVE: To predict the knee's response to isometric quadriceps contractions against a fixed tibial restraint.Design. Mathematical modelling of the human knee joint. BACKGROUND: Isometric quadriceps contraction is commonly used for leg muscle strengthening following ligament injury or reconstruction. It is desirable to know the ligament forces induced but direct measurement is difficult. METHODS: The model, previously applied to the Lachmann or 'drawer' tests, combines an extensible fibre-array representation of the cruciate ligaments with a compressible 'thin-layer' representation of the cartilage. The model allows the knee configuration and force system to be calculated, given flexion angle, restraint position and loading. RESULTS: Inclusion of cartilage deformation increases relative tibio-femoral translation and decreases the ligament forces generated. For each restraint position, a range of flexion angles is found in which no ligament force is required, as opposed to a single flexion angle in the case of incompressible cartilage layers. CONCLUSIONS: Knee geometry and ligament elasticity are found to be the most important factors governing the joint's response to isometric quadriceps contractions, but cartilage deformation is found to be more important than in the Lachmann test. RELEVANCE: Estimation of knee ligament forces is important when devising exercise regimes following ligament injury or reconstruction. The finding of a 'neutral zone' of zero ligament force may have implications for rehabilitation of the ligament-injured knee.

The variation in the orientations and moment arms of the knee extensor and flexor muscle tendons with increasing muscle force: a mathematical analysis.

The orientations and moment arms of the knee extensor and flexor muscle tendons are evaluated with increasing values of muscle force during simulated isometric exercises. A four-bar linkage model of the knee in the sagittal plane was used to define the motion of the joint in the unloaded state during 0-120 degrees flexion. The cruciate and collateral ligaments were represented by arrays of elastic fibres, which were recruited sequentially under load or remained buckled when slack. A bi-articular model of the patello-femoral joint was used. Simple straight-line representation was used for the lines of action of the forces transmitted by the model muscle tendons. The effects of tissue deformation with increasing muscle force were considered. During quadriceps contraction resisted by an external flexing load, the maximum change in moment arm of the patellar tendon was found to be 2 per cent at 0 degree flexion when the quadriceps force was increased tenfold, from 250 to 2500 N. The corresponding maximum change in orientation of the tendon was 3 degrees at 120 degrees flexion. During hamstrings contraction resisted by an external extending load, the maximum change in moment arm of the hamstrings tendon was 8 per cent at 60 degrees flexion when the hamstrings force was increased tenfold, from 100 to 1000 N. During gastrocnemious contraction, the corresponding maximum change for the gastrocnemious tendon was 3 per cent at 0 degree. The orientations of the flexor muscle tendons in this range of force either remained constant or changed by 1 degree or less at any flexion angle. The general trend at any flexion angle was that, as the muscle force was increased, the moment arms and the orientations approached nearly constant values, showing asymptotic behaviour. It is concluded that experimental simulations of knee muscle action with low values of the externally applied load, of the order of 50 N, can provide reliable estimates of the relationships between muscle forces and external loads during activity.

The effect of cartilage deformation on the laxity of the knee joint.

In this paper, deformation of the articular cartilage layers is incorporated into an existing two-dimensional quasi-static model of the knee joint. The new model relates the applied force and the joint displacement, as measured in the Lachmann drawer test, and allows the effect of cartilage deformation on the knee joint laxity to be determined. The new model augments the previous knee model by calculating the tibio-femoral contact force subject to an approximate 'thin-layer' constitutive equation, and a method is described for finding the configuration of the knee under a specified load, in terms of a displacement from a zero-load reference configuration. The results show that inclusion of deformable cartilage layers can cause a reduction of between 10 and 35 per cent in the force required to produce a given tibial displacement, over the range of flexion angles considered. The presence of cartilage deformation was found to be an important modifier of the loading response but is secondary to the effect of ligamentous extension. The flexion angle dependence of passive joint laxity is much more strongly influenced by fibre recruitment in the ligaments than by cartilage deformation.

Pattern of HIV-infection in Hurungwe district, Mashonaland West, Zimbabwe.

After the first case of HIV-infection had been diagnosed in 1986 in a Northern district of Zimbabwe, a local hospital based surveillance system, was introduced. In order to monitor the spread of the epidemic in the district, residence, age, sex and clinical presentation of all newly diagnosed HIV-patients were recorded. After three years, the data were compiled and analysed with the following results. Altogether 887 symptomatic HIV-patients (0.5 pc of the district population) were diagnosed. The most common HIV-associated signs and symptoms were PGL (47 pc), chest infection (29 pc), herpes zoster (24 pc) and chronic STDs (15 pc). The female-to-male ratio in adults was 1.4. The average age on diagnosis in women was 26.0 +/- 6.7 years and in men 30.7 +/- 8.6 years. The three years' cumulative incidence of HIV-cases was 27.2/1,000 in the urban area and 3/1,000 in the rural areas of the district.

PIP: Data on 887 AIDS cases in Zimbabwe were collected at the District Hospital in Hurungwe, Zimbabwe, from 1986-89 before the official notification system included this disease. The number of cases increased from 19 in 1986 to 290 in 1987, 433 in 1988, and 145 in the first 3 months of 1989. The female male ratio in adults were 1.4. There were 102 children under 5 with AIDS and the 5 children aged 5-15, who were all female. The presenting signs and symptoms were most often persistent generalized lymphadenopathy, chest infection, herpes zoster, chronic STDs, and chronic diarrhea with weight loss. There were 44 cases of HIV-positive pulmonary tuberculosis; 8 patients being treated for tuberculosis developed Stevens-Johnson syndrome. Of patients, overall, with herpes zoster, 89% were HIV-positive, of those with oral thrush, 83% were HIV-positive, of those with generalized lymphadenopathy, 76% were HIV-positive, and of those with weight loss and chronic diarrhea, 70% were HIV-positive. The Hurungwe District lies along the road from harare to Lusaka, Zambia, where long-distant truck drivers frequently interact with the locally mobile population. The authors suggest that herpes zoster, with its ease of diagnosis, be used as a tool to follow the spread of HIV.