Reducing overnight secretion of acid to heal duodenal ulcers. Comparison of standard divided dose of ranitidine with a single dose administered at night.

This study was undertaken to assess the clinical usefulness of a single nighttime dose of ranitidine in the short-term healing of duodenal ulcer. One hundred and nine patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with ranitidine, either 150 mg twice daily or 300 mg as a single nighttime dose for four weeks, in a prospective double-blind, double-placebo trial. Of the 102 patients who completed the study, 48 of 57 (84 percent) healed endoscopically on ranitidine 150 mg twice daily, and 43 of 45 (96 percent) healed on 300 mg at nighttime (Mantel-Haenszel test without continuity correction: X2 = 2.9, p = 0.09). One patient treated with ranitidine 150 mg twice daily had a transient episode of cholestatic hepatitis that did not necessitate stopping the drug; in this patient the ulcer healed after 28 days of treatment. There were no other unwanted effects in either group and no significant abnormal biochemical or hematologic changes. This study shows that ranitidine 300 mg given as one nighttime dose is as safe as 150 mg twice daily, and equally as effective. Three hundred milligrams at night appear to confer protection against the adverse effect of smoking in ulcer healing.

Phenotypic heterogeneity and recycling capacity of natural killer cells in normal human pregnancy.

Natural killer (NK) cells have the ability to kill a variety of target cell types and the possibility that such cells could mount an effective attack on the developing fetus has not been discounted. The present study extends previous work showing that maternal NK reactivity against K562 target cells (TC) is reduced during pregnancy. Here we demonstrate using cytotoxicity assays at both the population and single cell level that, although depressed in number, maternal NK cells exhibiting the capacity to kill K562 TC are as lytically active in their ability to recycle and destroy multiple TC as NK cells from non-pregnant females. Moreover, two colour immunofluorescence analysis of the NK cell-associated markers Leu-7 and Leu-11b indicates that, in addition to a reduction in the absolute number of TC conjugate-forming cells, pregnant females present in their peripheral blood a larger proportion of TC-binding Leu-7+11- cells. These cells may be lytically immature. Small changes in NK cell profile and activity in maternal peripheral blood may be indicative of much more significant changes at the feto-maternal interface. It is, however, clear that pregnant females retain a population of highly active NK cells, thus minimising the possibility of immunocompromise.

Cytotoxic activity and phenotypic analysis of natural killer cells in early normal human pregnancy.

Peripheral blood lymphocytes taken from healthy women planning a pregnancy and then at various intervals up to the 16th week of pregnancy were assayed for natural killer (NK) cell activity against K562 target cells both in a 51Cr-release assay and in a single cell cytotoxicity assay. Results indicated a depression in NK activity from the earliest stages of pregnancy. The target binding capacity of the effector cells remained unimpaired up to 16 weeks, but a significant reduction in the post-binding lytic potential was observed, which parallelled the drop in cytotoxicity as assayed by the 51Cr-release method. The ability of individual effector cells to recycle and kill multiple targets remained essentially unimpaired. Analysis of lymphocyte subpopulations using the monoclonal antibodies anti-Leu-7 and anti-Leu-11b, which recognize NK cell-associated antigens, showed a significant reduction in the proportion of the mature, lytically active Leu-7-11+ cells capable of both binding and lysing K562 target cells. The suggestion that the depression in cytotoxicity may be associated with the reduction in the Leu-7-11+ subpopulation is supported by the high correlation levels observed between the proportion of Leu-7-11+ cells and target cell lysis.

Multiple immunological abnormalities in a family.

The family of a woman with multiple autoimmune diseases has been investigated. Clinical evidence of an autoimmune disorder was detected in two relatives, and five others had serological and immunoglobulin abnormalities. It is suggested that there is an inherited predisposition to develop immunological abnormalities, and that a number of associated autoimmune diseases may develop in families in which this occurs.

Photosensitization of Staphylococcus aureus with malachite green isothiocyanate: inactivation efficiency and spectroscopic analysis.

The potential of malachite green isothiocyanate as a photosensitizer for the inactivation of bacteria has been evaluated. Samples of Staphylococcus aureus are treated with the dye and exposed to continuous-wave red light from a filtered xenon lamp. Reduction in cell viability is seen to increase with radiation dose, whilst non-photosensitized samples are largely unaffected with exposure. The mechanism of photosensitization and the subsequent inactivation is addressed. UV-Vis and Fourier-transform infrared absorption spectrometry have been applied to this biological system, revealing the rapid hydrolysis of the isothiocyanate group of the dye and the transition to the colourless carbinol base when in solution. On binding to Staphylococcus aureus via a complexation mechanism, the dye is seen to be stabilized in its cationic form. Involvement of the excited triplet state of the photosensitizer is suggested and identification of reduced dye photoproducts is made following irradiation.

Hyperglobulinaemic renal tubular acidosis: a report of nine cases.

Of nine women with hyperglobulinaemic renal tubular acidosis four presented with acidosis and five had the "incomplete" form of the disorder. Seven patients had nephrogenic diabetes insipidus, but none had the Fanconi syndrome. Investigation showed abnormal immunoglobulins and autoantibodies in all nine patients. Diseases coexisting with renal tubular acidosis were Sjögren's syndrome, hyperglobulinaemic purpura, autoimmune liver and thyroid disease, diffuse pulmonary fibrosis, and a peripheral neuropathy. It is suggested that this type of renal tubular acidosis might be due to an autoimmune process.

Renal tubular acidosis and autoimmune liver disease.

Forty-two patients with autoimmune liver disease have been investigated. Renal tubular acidosis was detected in 60% of the patients with primary biliary cirrhosis, in 30% with active chronic hepatitis, and in one out of seven cases with cryptogenic cirrhosis. The presence of the defect of renal acidification was not related to the level of plasma potassium, copper, or total globulin, nor to the pattern of immunological abnormalities detected in the serum. It is suggested that autoimmune liver disease and renal tubular acidosis may be part of a systemic disorder in the pathogenesis of which immunological mechanisms are involved.

Dermatomyositis associated with malignant melanoma--case report and review of the literature.

Dermatomyositis (DM) is a connective tissue disorder characterized by cutaneous and muscle involvement. It is a well recognized paraneoplastic syndrome and has been linked with malignancy in 15-34% of adult patients. The course of DM in such patients usually correlates closely with the activity of the underlying malignancy. We report a patient who developed DM 4 years after excision of a malignant melanoma (MM) from the back and 1 year before the diagnosis of metastatic disease. A literature review revealed that the association of dermatomyositis with MM is rare and consistent with a dismal prognosis.

Non-Hodgkin's lymphoma arising in skeletal muscle.

Four patients with non-Hodgkin's lymphoma who presented with clinical enlargement of muscle are reported. In three patients the only site of disease was muscle. Two patients with involvement of the paraspinal muscles demonstrated neurological complications due to spinal nerve root entrapment. A review of the literature emphasises the rarity of primary muscle lymphoma and suggests that disease arising at this site may confer a poor prognosis.

Medical presentations of choriocarcinoma.

Choriocarcinoma commonly presents with symptoms resulting from metastases in the lungs, central nervous system, or alimentary tract. This tumour may occur without any gynaecological symptoms and when pelvic examination and uterine curettage show no abnormality. Several years may elapse between the antecedent pregnancy and presentation with metastatic disease. The ability to eradicate these tumours with present chemotherapeutic methods depends on detecting their presence as soon as possible after the antecedent pregnancy.Wider recognition of the varied manifestations of metastatic choriocarcinoma and greater use of tests for chorionic gonadotrophin should result in earlier diagnosis and an improved prognosis in these patients. In particular, such tests should be made in patients with unexplained intracranial haemorrhage, progressive dyspnoea, and gastrointestinal haemorrhage.

Choriocarcinoma after hydatidiform mole. Studies related to effectiveness of follow-up practice after hydatidiform mole.

Chemotherapy, in conjunction with other methods of treatment, was used in 100 patients with invasive hydatidiform mole or choriocarcinoma following mole. When treatment was instituted within two to six months of the antecedent mole serious drug resistance was not encountered, drug toxicity was slight, the duration of treatment was comparatively short, and sustained remissions were obtained in 57 out of 60 patients. When the start of chemotherapy was delayed beyond six months drug resistance occurred in many instances, toxicity was often severe, the duration of treatment was much longer, and sustained remissions were obtained in 22 out of 40 patients.The practice of giving prophylactic chemotherapy to all patients with mole is not established as effective or safe. Differences in the social background to hydatidiform mole in different geographical areas may be such that conclusions based on evidence from one area are not necessarily applicable to another.Careful follow-up after mole remains essential, though present methods often fail to ensure recognition of choriocarcinoma while it is still curable. Standard qualitative and quantitative methods for detecting the continued excretion of chorionic gonadotrophin, though useful, are sometimes too insensitive. It is suggested that to supplement local arrangements some form of centralized or regionalized follow-up service based on notification of patients with hydatidiform mole, and making use of radioimmunoassays for chorionic gonadotrophin, could reduce deaths attributable to late diagnosis.

"Sicca complex" in liver disease.

Sixty-three patients with liver disease were studied for the presence of the components of Sjögren's syndrome. The "sicca complex" (that is, patients without arthritis) was detected in 42% of patients with active chronic hepatitis, 72% with primary biliary cirrhosis, and 38% with cryptogenic cirrhosis. One patient with active chronic hepatitis and one with primary biliary cirrhosis had rheumatoid arthritis. No evidence of Sjögren's syndrome was detected in seven patients with alcoholic cirrhosis. It is suggested that the sicca complex and autoimmune liver disease may be part of a systemic disorder in which immunological mechanisms are concerned in the pathogenesis.

Fibrosing alveolitis associated with renal tubular acidosis.

The discovery of a case of renal tubular acidosis and fibrosing alveolitis led to the investigation of 19 further patients. Abnormal pulmonary function tests were found in a further four patients with overt renal tubular acidosis and in four out of eight patients with "incomplete" renal tubular acidosis. The response to an ammonium chloride test in seven patients with cryptogenic fibrosing alveolitis was normal. Those patients with a defect of both renal acidification and pulmonary gas transfer had concurrent autoimmune diseases such as Sjögren's syndrome and primary biliary cirrhosis. It is suggested that the renal and pulmonary abnormalities may be part of a systemic disorder capable of affecting many organs. Moreover, hyperglobulinaemia and autoantibodies in these patients further suggests that immunological mechanisms are concerned in the pathogenesis of these abnormalities.

Cytotoxic reactivity of human natural killer (NK) cells during normal pregnancy: a longitudinal study.

A longitudinal analysis of natural killer (NK) cell-mediated cytotoxicity of maternal peripheral blood lymphocytes was carried out at various stages (16-36 weeks) of normal human pregnancy, within 1 week following delivery and up to 40 weeks post-partum. NK cell-mediated lysis of K562 target cells (TC) in short term 51Cr-release assays was significantly depressed throughout pregnancy, returning to control levels 9-40 weeks post-partum. Natural cytotoxicity of unseparated maternal peripheral blood was also substantially depressed at all stages of pregnancy and, in addition, remained impaired in the late post-partum period. Longitudinal enumeration of Leu 3a+ and Leu 2a+ lymphocytes indicated an absence of helper/suppressor T-cell imbalance during pregnancy, and analysis of Leu 7+ cells showed no difference in population sizes between control and pregnancy groups. Comparison of blood and lymphocyte cytotoxicity in control and pregnancy samples suggested a complex regulation of NK reactivity during pregnancy. The potential role in vivo of both plasma-associated and cellular regulatory elements is discussed.