Relapse with transformation of lupus nephritis in a transplant kidney.

Lupus nephritis is a constellation of different renal histologies, characterized by an immune complex mediated glomerular disease. Histological transformation in lupus nephritis usually occurs from a mild mesangial proliferative glomerulonephritis to a more aggressive diffuse proliferative lesion. We present a case of relapsed systemic lupus erythematosus (SLE) in a renal transplant recipient in which there was a histological transformation from the original diffuse proliferative lupus nephritis in the native kidneys to a membranous lupus nephritis in the renal transplant.

Clinical outcomes of the Otago-Southland Breast Cancer Screening Programme 1991-1996.

AIM: To document the clinical outcome of the Otago-Southland Breast Cancer Screening Programme through its first two rounds of screening, from 1991-1996. METHODS: Review and analysis of clinical and pathological records. RESULTS: In the first round of screening, 13,876 women were screened, giving 75% uptake; 12.2% were referred for assessment and 126 cancers detected, 9.1 per thousand women screened. For the 9946 incidence screens in the second round, 3.9% of women screened were referred to assessment and 50 cancers detected, 5.0 per thousand women screened. The uptake and cancer detection rates exceed the targets and exceed other published results; the size distribution of the cancers detected was comparable to the Swedish two-counties study, showing that the results should produce an ultimate mortality reduction. The referral rate to assessment was higher than expected in the first round of screening, but within the targeted range in the second round. The benign to malignant ratio for all biopsies was 1.4:1 for the prevalence screen of the first round and 1.2:1 for the incidence screens in the second round, both exceeding the targets set. CONCLUSIONS: The results show that the uptake and clinical results of the programme exceed expectations and that a large number of small invasive tumours have been successfully detected. These results are comparable to the best of overseas studies, and give confidence that mortality reductions will ultimately occur.

Withdrawal reactions associated with venlafaxine.

OBJECTIVE: The aim of this paper is to describe discontinuation syndromes associated with abrupt and tapered withdrawal fo venlafaxine, and to document that withdrawal symptoms may occur after missing a single dose. CLINICAL PICTURE: We report on two patients prescribed venlafaxine. One developed a broad range of serious side effects after reaching a dose of 300 mg a day, and a severe withdrawal syndrome (including hallucinations) during a slow taper regime. The second had severe discontinuation symptoms during and aborting a slow taper regime, and described withdrawal responses after missing a single dose of venlafaxine. CONCLUSIONS: As for the short-acting selective serotonin re-uptake inhibitors, severe discontinuation reactions may occur with venlafaxine, seemingly marked most distinctly by headache, nausea, fatigue, dizziness and dysphoria, and may make cessation of the drug extremely difficult. Two strategies for addressing the concern are considered.

Shock lung and diffuse alveolar damage pathological and pathogenetic considerations.

Diffuse alveolar damage may be caused by any one or more of a large number of injurious agents. While the etiology may be diverse, the pathology is relatively uniform ranging from an acute exudative phase characterized by protein-rich interstitial and alveolar edema, through to a reactive subacute proliferative phase characterized by interstitial fibroplasia and collagenization together with granular pneumocyte hyperplasia. Interstitial inflammation is a variable feature and of course mixed exudative and proliferative features are common. In the clinically overt adult respiratory distress syndrome, the mortality is formidable. The pathogenesis is damage to endothelial cells and membranous pneumocytes. This may be caused by direct chemical action or indirectly through the mediation of oxidizing free radicles or leukotrienes. In diffuse alveolar damage associated with shock, recent work suggests mediation of the cellular injury via complement activation following tissue injury, with the major pathology being due to lysosomal enzyme damage from phagocytes chemotactically attracted to the lung. Etiological factors in diffuse alveolar damage are numerous and details of appropriate primary therapy are therefore diverse. The pathogenesis and pathology are however relatively uniform, calling for uniform supportive therapeutic measures of the clinical adult respiratory distress syndrome.

Pseudo-lymphocyte monocytes--the memory cells responsible for the development of epitheloid cell granulomata. A new hypothesis.

This hypothesis proposes that, in individuals with an appropriate genetic background, monocyte memory cells are formed when histiocytes and macrophages undergo mitosis following first exposure to a granulomagenic agent and circulate as pseudolymphocytes in the lymphocyte null cell population. It is proposed that epithelioid cell granulomata develop from a clone of cells formed from monocyte memory cells on the second or subsequent exposure to the same granulomagenic agent. Epithelioid cell granuloma formation is therefore not dependent on T-cell function, although the cellular nature of the granuloma appears to depend upon the nature of a concomitant but independent classical immune response. The implications of pseudolymphocyte memory cells on the development of granulomata of both exogenous and endogenous origin, and the relationships between lymphocytes and cells of the monocytic phagocyte series are discussed.

Muramidase content of cells in human granulomatous reactions.

The muramidase content of reactive cells in the lesions of human foreign body reactions, lepromatous and tuberculoid leprosy, sarcoidosis, tuberculosis, and granulomatous hepatitis, was assessed using specific anti-human muramidase antiserum and a peroxidase-anti-peroxidase marker system. Epithelioid and giant cells in sarcoidosis, tuberculosis, granulomatous hepatitis, and tuberculoid leprosy all showed the presence of muramidase in their cytoplasm. The muramidase content of macrophages in foreign body reactions and lepromatous leprosy varied and most multinucleate cells in these lesions gave a negative reaction. Possibly varying rates of muramidase secretion may account for these differences.

Experimental granulomatous inflammation: the ultrastructure of the reaction of guinea pigs to bentonite injection.

Bentonite, a silicate, induces a classical non-immunological foreign body reaction when injected intradermally into guinea pigs. The cellular response consists of a mass of macrophages and large macrophage polykaryons, surrounded and infiltrated by an extensive fibrous reaction. The bentonite granuloma shows no signs of intercellular organisation of the reacting cells. Study of its ultrastructure suggests a low turnover lesion with a stable, long-lived cell population. The bentonite granuloma is contrasted with the tuberculous, immunologically mediated epithelioid cell granuloma produced in sensitised guinea pigs.

Experimental granulomatous inflammation: the ultrastructure of the granuloma induced by injection of tubercle bacilli into Freund adjuvant-sensitised guinea-pigs.

Injection of killed tubercle bacilli into a sensitised guinea pig produces a characteristic biphasic response with the development of an organised epithelioid cell granuloma in the second phase. Previous sensitisation to tubercle bacilli is a requirement for development of the organised granulomatous response. The main components of the granuloma are epithelioid cells, although multinucleate cells of both Langhans and foreign-body type are present. Epithelioid cells appear to evolve from monocytes, probably in the sequence: (a) monocyte, (b) monocytic transition form, (c) immature epithelioid cell, (d) mature epithelioid cell, although some may possibly develop through a macrophage stage. Differentiation of monocytes into epithelioid cells is a continual process in the experimental tuberculous granuloma with monocytes migrating into the lesion at all stages examined. Epithelioid cells are not obviously phagocytic. Their differ4ntiation has a phase suggestive of biosynthesis during which RER is the predominant cytoplasmic component. This is followed by a storage/secretory phase in which the cytoplasm contains membrane-lined vesicles and prominent Golgi apparatus. The vesicles and, where distended, the RER laminae contain a lightly staining, finely granular material the biological activity of which is unknown.

Experimental granulomatous inflammation: I. Gross and light microscopical observations in freund adjuvant-sensitized Cavies following the injection of killed tubercle bacilli.

The tuberculous granuloma, induced by injection of microgram doses of killed mycobacteria into guinea pigs sensitized by injection of Freund adjuvant is immunologically mediated. Formation of the granuloma is preceded by development within 24 h of a lymphocyte-dominated mononuclear cell response typical of a delayed hypersensitivity (type IV immune response) reaction. About the sixth day, following a marked decrease in intensity of the cellular reaction, a nodule containing monocytes and macrophages develops at the injection site. With increasing numbers of monocytes and macrophages the nodule forms a non-caseating granuloma with giant cells but dominated by epithelioid cells and reaching a maximum size about 3 wk after injection. Thereafter the granuloma undergoes gradual demolition being replaced and surrounded by fibroblasts and collagen deposition. The very delayed nature of this immune response as well as its histological character appear clearly to separate it from classical cell-mediated and humoral immune responses. These facts justify the hypothesis of a third type of (usually protective) immune response characterized histologically by the development of an epithelioid cell granuloma and determined by the nature of the antigenic material and the reactivity of the host. The initial polymorphonuclear leucocyte reaction to injection of mycobacteria, being similar in sensitized and control animals, does not appear to be under immunological control.

Experimental granulomatous inflammation: II. Effect of injection of intact and disrupted killed tubercle bacilli into Freund adjuvant-sensitized Cavies.

The reaction of Freund adjuvant-immunized cavies to subsequent injection of Mycobacterium tuberculosis H37Ra is confirmed as an immunologically mediated phenomenon. Ultrasonic disruption of mycobacteria to be injected as "challenge" markedly increases the intensity of the consequent 24-48 h reaction and subsequent fibrosis in Freund adjuvant-sensitized cavies and has an apparently inhibiting effect on the extent of subsequent granuloma formation with marked reduction of the density of epithelioid cells. From this study, the 24-48 h reaction to injection of M. tuberculosis into sensitized animals appears clearly to be separable from subsequent granuloma formation depending upon the integrity or otherwise of the injected myocobacteria used as the challenge injection material.

Localized pulmonary Wegener's granuloma simulating lung cancer: report of four cases.

Clinical features suggesting lung disease in three patients and a chance chest radiograph in the fourth led to films showing localized lung lesions with some characteristics of neoplasms. Two were heavy smokers, two were non-smokers. In two the lesion was peripheral, in one lobar (RUL), and in the fourth it crossed the interlobar fissure (apical and posterior segments LUL and apical LLL). Malignant cells were not seen on sputum cytology examination in any, but in one, atypical cells were reported. All four patients had lung resection for suspected cancer, two by pneumonectomy, one by lobectomy, and one lingulectomy. All patients recovered, and their clinical course has so far been uniformly benign. Two have been followed long term (16 and 10 years), one 2 1/2 years, and one a year. Pathologically, the lesions appeared to be strictly limited without extra-pulmonary involvement, except that the patient followed for one year has developed hyporegenerative anaemia responsive to prednisone therapy. The pathological features of focal necrosis, granulomatous inflammation, and vasculitis were sufficiently striking, although often focal, to suggest that incisional biopsy from frozen-section histological diagnosis could be useful to prevent extensive lung resection for lesions not positively diagnosed before thoracotomy.