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Biomedical subjects

R J Rees

Publications and source records attributed to R J Rees.

At least 73 records · Page 4Linked to original sources

Evidence for prevention of borderline leprosy reactions by dapsone.

68 patients were included in a prospective study of the treatment of borderline leprosy. 34 were treated with dapsone 5 mg daily, and 34 with 50 mg daily. Reversal reactions developed in 11 of those on 5 mg daily and in 3 of those on 50 mg daily. The statistically significant difference between the two treatment groups indicates that, contrary to previous teaching, dapsone given in higher dosage does not predispose patients to reversal reactions and indeed may prevent them.

Adolescent↗

Transmissible agents from human sarcoid and Crohn's disease tissues.

Mice were inoculated with human sarcoid tissue homogenates or with a first or a second passage homogenate of mouse tissue (including 0.2 mum membrane filtrates) originating from the inoculation of human sarcoid, Crohn's disease, or control tissue homogenates. Epithelioid and giant cell granulomas were present in the footpads and/or viscera of some of the mice given homogenates originating from each sarcoid or Crohn's disease tissue 15 months after inoculation but were not present in mice given control homogenates. Among mice given homogenates originating from human sarcoidosis, granulomas were present in many organs and tissues; in contrast, a pattern of selective dissemination of visceral granulomas was found among mice given homogenates originating from Crohn's disease. This differential distribution of visceral granulomas also followed the inoculation of 0.2 mum membrane filtrates. Granulomatous responses at Kveim test sites in the ear 9-17 months after inoculation of homogenatesoriginating from human sarcoidosis or Crohn's disease were confined to mice showing granulomas in footpads of viscera. The ability of the transmissible agents to induce granulomas in mice was destroyed when sarcoid or Crohn's tissues were autoclaved or when sarcoid homogenates were stored at -20degreesC for 1 week or exposed to 60Co irradiation (2.5 MR).

Animals↗

Further observations on the transmissibility of Crohn's disease.

In controlled experiments normal and immunologically deficient CBA mice were inoculated with whole fresh, fresh autoclaved, fresh supernatant, or filtered supernatant (0.2 mu) of whole Crohn's or non-Crohn's homogenate into footpads, intraperitoneally or intravenously. Epithelioid and giant-cell granulomas were present in a substantial proportion the footpads and in bowel or mesenteric lymph nodes of a proportion of given each fresh Crohn's homogenate by any of these routes 15-17 months after inoculation, but were not present in mice given non-Crohn's or autoclaved Crohn's homogenate. Successful passages were achieved following the inoculation of Crohn's mouse tissue homogenates, including passage from mice receiving filtered supernatant (0.2mu) or whole Crohn's homogenate, into footpads or intravenously. The epithelioid- and giant-cell granulomas evolved slowly over a period of many months following the inoculation of Crohn's tissue or passage homogenates and persisted thereafter. The transmissible agent is inactivated when homogenate from Crohn's tissue is autoclaved, can be passaged successfully into footpads or intravenously, and has been shown to pass an 0.2 mu membrane filter. It is therefore presumably viable and must approximate to the size of a virus or be capable of being deformed to pass a filter of such a pore size (0.2mu).

Animals↗

Detection of immune complexes in mice infected with Mycobacterium lepraemurium.

A specific binding test was used to detect immune complexes containing antigens of Mycobacterium lepraemurium in the serum and tissues of infected mice. Complexes were precipitated by antiserum against immunoglogulin, free antigen removed by washing and the presence of bound antigen demonstrated by measurement of uptake of radioactively labelled specific antibody by the precipitate. Tests were done both with 125I-labelled FAB prepared from an immune from rabbit antiserum against M. Lepraemurium and with 125I-labelled IgG precipitate. Out of seventy-nine serum samples taken monthly up to the 5th month after infection, only there were positive (one at 2 months and two at 3 months). Kidneys taken from infected mice were also examined for immune complexes. Although deposits of IgM and sometimes of IgG were observed by immunoflourescence in glomeruli of normal mice, deposits of IgG were more frequent later on in infected mice. Nevertheless, binding tests done on acid eluates were positive in only one out of fifty-three infected mice.

Animals↗

Sulphone resistance in leprosy. A review of one hundred proven clinical cases.

An account is given of the first hundred consecutive proven cases of sulphone resistance in leprosy, detected in Malaysia between 1963 and 1974. Proof of resistance was clinical in eighty patients and was obtained by drug-sensitivity testing in mice in ninety-six patients; 76 cases were proved both clinically and experimentally, and there was no discrepancy between the two methods. Sulphone resistance was confined to patients with lepromatous-type leprosy--i.e., patients with a large bacterial population. Clinical evidence of relapse due to drug resistance appeared 5-24 years after the start of sulphone treatment. Low dosage favoured the appearance of resistance; therefore regular treatment of lepromatous leprosy with dapsone in full dosage is recommended. The attainment of "skin smears negative for leprosy bacilli" is no test of cure of lepromatous leprosy.

Adolescent↗

The testis in mice infected with Mycobacterium leprae.

Following inoculation either locally or intravenously with Mycobact. leprae of human origin, the histopathology and bacteriology of the testis in experimental mice is described. Normal mice, and mice rendered immunologically deficient by thymectomy and whole-body irradiation, were studied. Attention is drawn to a heavy bacillation of the testis in mice from both groups. Bacilli were found in and beneath the tunica albuginea, but mainly in interstitial cells and in macrophages surrounding the tubules. The percentage of solidly staining bacilli was high, and globi were frequent. The study showed that the testis in mice is particularly favourable for the lodgement and multiplication of Mycobact. laprae following either local or intravenous inoculation. The significance of this in relation to the metabolism of the leprosy bacillus and to the frequent occurrence of testicular damage in the lepromatous male patient is discussed. This work was supported by grants to A. G. M. Weddell and A. C. McDougall from the Medical Research Council and the British Leprosy Relief Association (LEPRA).

Animals↗

The histopathology of lepromatous leprosy in the nose.

On the basis of clinical, histological and bacteriological assessments, 31 patients in Central India were selected and classified as having active but early lepromatous leprosy and 4 patients as having early borderline leprosy. From the nose of each patient an average of 4 biopsies were taken from particular sites of the septum and turbinates either by punch biopsy or dissection with a scalpel. The nasal tissues from all the lepromatous patients contained many acid-fast bacilli; no bacilli or abnormalities were seen in nasal tissues from the borderline patients. The histopathology of these highly bacilliferous tissues is described. Bacilli were universally seen in macrophages, but they were also seen in blood monocytes and polymorphs, fibroblasts, squamous and pseudo-columnar epithelium, keratin, peri- and endo-neurial cells of tiny nerve bundles, erectile tissue, vascular plain muscle, perivascular histiocytes and frequently and abundantly in the cytoplasm of endothelial lining cells of lymphatics and of small blood vessels and free within the lumina of these vessels. Five basic mechanisms of escape of bacilli from the submucosa on to the surface, and thus into the external environment, are described. Secondary infection, in the presence of an expansile lepromatous infiltrate, together with simple trauma to the surface epithelium, are the main factors in the discharge of bacilli. These histopathological observations are consistent with the findings from other recent studies on the nose in leprosy regarding (1) the large numbers of morphologically intact and viable Myco. leprae excreted in the nasal mucus of lepromatous patients; (2) the clinical changes observed in the nose of such patients, and (3) the similar nasal involvement and excretion of Myco. leprae from the nose of mice inoculated with leprosy bacilli of human origin. Of particular interest was the frequency and intensity of bacilli within the endothelial lining cells of small blood and lymph vessels and the presence of bacilli free within the lumina of these vessels or within monocytes and polymorphs. The possible dynamic significance of these observations in the pathogenesis of leprosy is discussed. The significance of all these observations in relation to (1) the spread of leprosy; (2) local factors in the nose which might favour the growth of Myco. leprae, and (3) the nose as a portal of entry, are discussed.

Biopsy↗

The penetration of dapsone, rifampicin, isoniazid and pyrazinamide into peripheral nerves.

1 Dapsone, rifampicin, isoniazid and pyrazinamide were shown to penetrate readily into the sciatic nerves of the dog and sheep. 2 These findings suggest that the continued persistence of viable drug-sensitive leprosy bacilli in the peripheral nerves of patients treated for long periods with either dapsone or rifampicin is not due to inadequate intraneural drug penetration.

Animals↗

Preliminary taxonomic studies on the leprosy bacillus.

Antigens extracted from leprosy bacilli obtained from infected human and armadillo tissues have been examined by immunodiffusion analysis with serum samples from lepromatous patients and with immune sera raised in rabbits. Using the best combinations of serum and antigen extracts, 12 antigenic constituents were found in the leprosy bacilli. Six of these were antigens common to all mycobacteria and nocardiae, 4 were specific to the leprosy bacillus and the position of 2 could not be determined. Groups ii and iii antigens (i.e. those associated with the slow growing and fast growing subgenera of mycobacteria) were not found in theleprosy bacillus, suggesting some relationship with M. vaccae and similar strains, in which these antigens are also missing. Lymphocyte transformation tests performed on lymph node cells of mice infected or immunized with leprosy bacilli also showed the leprosy bacillus to have a closer relationship with M. vaccae than with other mycobacteria.

Animals↗