Summary We have studied an aspect of the functional heterogeneity of human mast cells, namely responsiveness to the inhibitory effects of sodium cromoglycate and nedocromil sodium. The effects of these drugs were examined on the release of histamine and PGD 2 from mast cells of human skin, lung, tonsils, adenoids and intestine. A high concentration, 1000 μM, of sodium cromoglycate was required to significantly inhibit histamine release from lung and tonsillar mast cells. Nedocromil sodium, 1000 μM, was more effective than sodium cromoglycate against histamine release from lung, tonsillar and adenoidal cells. Both compounds showed tachyphylaxis in lung and tonsillar mast cells but not in adenoidal and intestinal mast cells. In contrast, in intestinal mast cells, the effect of nedocromil sodium was weaker and more variable than sodium cromoglycate. Skin mast cells differed from mast cells of the other anatomical sites in being unresponsive to sodium cromoglycate and nedocromil sodium. Our results confirm that high concentrations of sodium cromoglycate and nedocromil sodium are required to achieve even modest inhibition of mediator release from human mast cells under in vitro conditions. Notwithstanding this, the results also indicate that differences exist among skin, lung, tonsillar, adenoidal and intestinal mast cells with respect to their sensitivity to sodium cromoglycate and nedocromil sodium, thus extending our knowledge of functional heterogeneity within the human mast cell populations.

We have demonstrated that, unlike mast cells of the lung, adenoids, tonsils and intestine, whose primary role is thought to be IgE-mediated host defence, human skin mast cells respond to neuropeptide stimulation with a rapid release of histamine and minimal generation of PGD2 and LTC4. This ability of skin mast cells to release mediators in response to neuropeptide stimulation is evidence in favour of a neuro-immune interaction within human skin which may have evolved to promote angiogenesis [70] or control cutaneous blood flow [71]. In this context, it is interesting to note that mast cells are found in particularly high numbers in the blush areas of the neck and face [72].

The use of a collagenase dispersion technique has allowed us to compare size, histamine content and the secretory characteristics of mast cells from the mucosal and muscle layers of the human large intestine. Mast cells from the mucosa, which constituted 1.8% of the total nucleated cells, contained approximately equal numbers of formalin-sensitive and -insensitive mast cells. Those dispersed from the muscle layer constituted 3.2% of the total nucleated cells and were almost all formalin insensitive. The cells from both layers were similar with respect to size and mean cell histamine content. Anti-IgE released up to 15.1% and 16.5% of total cell histamine in the mucosa and muscle, respectively, with similar concentration-response characteristics. The kinetics of anti-IgE-induced release, however, were different, mucosal mast cells releasing histamine 55 seconds (P less than 0.05) faster than cells dispersed from intestinal muscle. Cells from both layers also released histamine in response to A23187 in a similar concentration-related fashion. Neither mucosal or muscle mast cells released significant amounts of histamine in response to compound 48/80, substance P, morphine, poly-L-lysine or f-met-leu-phe. Our results show intestinal mast cells possess secretory characteristics similar to those of human lung, adenoids and tonsils, but are different from human skin mast cells. The absence of significant histamine release in response to basic secretagogues from either layer of the human intestine contrasts with studies in the rodent intestine. Furthermore it suggests that in human mast cells, histochemical properties, protease content and secretory characteristics may not be closely associated.

We have compared the ability of anti-IgE, calcium ionophore A23187, substance P, compound 48/80, poly-L-lysine, and morphine to release histamine from mast cells of human skin, lung, adenoids, tonsils, and colon. Use of a single collagenase/hyaluronidase dispersion technique for all tissues has allowed comparisons of reactivity to be made that are free from methodological variations. Mast cells from all tissues examined secreted histamine in response to anti-IgE and calcium ionophore A23187. However, only skin mast cells were responsive to substance P, compound 48/80, poly-L-lysine, and morphine. Activation of human skin mast cells by these nonimmunologic stimuli clearly distinguishes them from the mast cells of human lung, adenoids, tonsils, and colon and is indicative of functional heterogeneity within the human mast cells population. We propose that the presence of functional receptor sites for neuropeptides and basic compounds on skin mast cells that are not present in mast cell populations from mucosal or lymphoid sources reflects a specialized role for these cells in vascular homeostasis.

The use of a second generation synthetic casting tape for the manufacture of functional foot orthoses is reported. The material is lightweight, strong, inexpensive and moulds intimatelyto the contours of a plaster model without the use of special heating apparatus. Because of the laminate structure of the orthosis, it has advantages in being capable of offering localized flexibility over thermoplastic materials of a uniform thickness. The mechanical strength of the material is also reported, comparing it with the same material laminated without vacuum assistance. Of the parameters studied (impact energy, tensile and four point bending strengths) a typical increase of between 100% and 200% is achieved by the vacuum forming process, together with an improvement in surface texture.

The authors have investigated the effect on the torsional strength of the bone of reaming the medulla of the femur from 12 to 16 mm in steps of 1 mm. Five groups of femurs, with 10 pairs in each, were tested comparatively in torsional loading and the torque required to cause fracture and the angle through which the bone had twisted at fracture were directly recorded for each pair. The results of maximum torque at failure (expressed as a proportion of the same parameter for the unreamed femur) plotted against the ratio of bone shaft diameter to reamed diameter showed a good correlation. The proportional maximum torque was found to range from 0.63 (at 12 mm) to 0.36 (at 16 mm) with a sharp transition between 14 and 15 mm. This drastic reduction was felt to be important for both the surgeon and the patient.

Due to the increase in prescription of insoles to relieve symptoms due to skeletal shocks at heel strike a pilot study was initiated to look at some materials used for this purpose. Five materials were examined (Plastazote, Spenco, Sorbothane, Poron (PPT) and Viscolas) by two methods. The first method used an accelerometer mounted between the teeth of one of the authors (PR) to record skeletal shock. The second method used a force plate to record the shock produced by dropping a ball-bearing onto the insoles from a standard height. The results showed that Plastazote is poor at absorbing shock with Spenco and Sorbothane being quite good. The best insole materials tested were Poron (PPT) and Viscolas with the latter being marginally superior. No account was taken of degradation of the materials in use except that Plastazote worn for 72 hours was also used in the study, this producing the worst results.

Twenty-one tests on 13 volunteer subjects were used to quantify cast stresses and intra-cast pressures in below knee casts during normal walking. A microcomputer and force plate system were used to study the gait with various cast configurations. It was found that stresses were high where expected but also in less obvious locations, i.e. anterior and posterior aspects of the upper part of the cast. The data suggest that, irrespective of the design of the cast (as long as it is well fitting), control of rotation will be sufficient. This also validates the use of an articulating ankle component in most situations, although this type of cast provides less rotation control. If a fixed ankle is used then the casting material should be concentrated around the junction of foot and shank cylinders and less on the shank (only sufficient to provide rigidity). Comparison of different materials indicates that use of modern casting materials requires more emphasis on splint construction details than when using conventional plaster of Paris.

Due to the increase in prescription of insoles to relieve symptoms due to skeletal shocks at heel strike a pilot study was initiated to look at some materials used for this purpose. Five materials were examined (Plastazote, Spenco, Sorbothane, Poron (PPT) and Viscolas) by two methods. The first method used an accelerometer mounted between the teeth of one of the authors (PR) to record skeletal shock. The second method used a force plate to record the shock produced by dropping a ball-bearing onto the insoles from a standard height. The results showed that Plastazote is poor at absorbing shock with Spenco and Sorbothane being quite good. The best insole materials tested were Poron (PPT) and Viscolas with the latter being marginally superior. No account was taken of degradation of the materials in use except that Plastazote worn for 72 hours was also used in the study, this producing the worst results.

A cheap and fast method of providing long term accommodating insoles is described. Room temperature vulcanizing (RTV) silicone rubber is used, with suitable coverings, to provide pain relief and support for feet and ankles. The combination of physical properties of the finished item provides a useful balance between support and flexibility which results in these insoles being readily accepted by the patients.

Sixty four Kenyan patients with visceral leishmaniasis were treated with sodium stibogluconate (Pentostam) (40 patients) or various combinations of Pentostam and allopurinol (24 patients). Three patients, initially considered cured after Pentostam, relapsed but responded to further treatment. Sixty two were cured and two patients died. The treatment and the clinical, haematological and parasitological response to treatment are described in detail. If follow up is impossible or unlikely it is advised to continue treatment until parasitological cure is obtained. Prolonged courses of Pentostam, which were required in some patients, resulted in cures and apparently were non toxic. Consideration is to be given to extended treatment with Pentostam before more toxic drugs such as pentamidine and amphotericin B are given.

At the beginning of the century, splenectomy was used in the treatment of kala-azar, but now is rarely needed, the major indication being for drug resistant kala-azar. Inadvertent splenectomy prior to the diagnosis of kala-azar continues to occur, probably because of a reluctance to perform splenic aspiration in the investigation of splenomegaly. Five Kenyan children underwent splenectomy for drug resistant kala-azar. All were immediately improved, but one died of overwhelming post splenectomy infection (OPSI) two months later and another of a malignant lymphoma seven months after surgery. The other three patients appear to be cured. Splenectomy was considered in a sixth child with kala-azar because of a Salmonella abscess in the spleen, but the abscess ruptured catastrophically before surgery could be arranged.

Of 16 patients with kala-azar treated with sodium stibogluconate (0.1 ml/kg body weight a day), one died on the 12th day of treatment and nine were cured by a 30-day course, although two subsequently relapsed. Extending the course cured a further five patients, and in one patient allopurinol was used in addition before a cure was achieved. Clinical and hematological recovery began within a few days of the start of treatment, but parasites continued to be seen in splenic aspirates for 3 weeks or more.

We describe the technique of splenic aspiration in 113 patients presenting with splenomegaly. It was used initially to establish a diagnosis, and in those patients with kala azar, to follow the response of the parasites to therapy until 'parasitological cure'. In all 671 aspirations were performed. No complications occurred in the 69 patients with active kala azar, who collectively had more than 600 aspirations. One patient in a moribund condition had a fatal haemorrhage. The aspirate suggested a lymphoma, confirmed at autopsy. In 68 of the 69 patients with active kala azar, the diagnosis was established at the first aspiration. The essentials of the technique are the use of a small calibre needle (21 G), and speed, the needle being in the spleen for less than a second, with the consequent procurement of a few drops of material only.

Clinical and laboratory findings of a series of 64 consecutive patients with visceral leishmaniasis are presented. The diagnosis was established by demonstration of parasites in splenic aspirates. Findings are discussed in comparison with those of former reports from Kenya and elsewhere.

As part of the study of the pancytopenia of kala azar, levels of complement factors and of circulating immune complexes were measured in 12 patients. High levels of C1q, in contrast to normal or even decreased C1s levels, were found. C3, C4, and C9 were more or less normal. High levels of circulating immune complexes, as measured by the 125I-C1q binding test, were found in all. The concentrations of C1q and of circulating immune complexes fell over a period of months but clinical and parasitological cure with successful treatment preceded the fall. Thus it seems unlikely that the elevated levels of circulating immune complexes are directly responsible for the pancytopenia that is a characteristic of kala azar.

Allopurinol was used in the treatment of 10 patients with kala-azar. Of six patients who had previously failed to respond satisfactorily to Pentostam, "cures" were achieved in four. However, it was necessary to add Pentostam to the allopurinol in one, and another relapsed after apparent "cure" but again responded to allopurinol. The response of four patients who had had no previous treatment for kala-azar was less satisfactory.

In 66 patients with active kala-azar, tuberculin skin tests were negative. During follow-up after apparently successful cure, some patients developed positive tuberculin skin tests. This suggests that active kala-azar is associated with a generalized, non-specific depression of cell-mediated immune responses, which reverts to normal after treatment.

Schneider's insect culture medium, supplemented by the addition of 30% (vv) heat-inactivated foetal bovine serum plus 100 IU penicillin and 100 μm streptomycin (final concentration per ml), is shown to be simple to use in the diagnosis and management of visceral leishmaniasis in Kenya. It is especially valuable because small numbers of parasites can be detected in this culture medium later during the course of treatment.