Massive rectal bleeding due to intestinal tuberculosis. Two cases of massive rectal bleeding due to tuberculosis of the intestine are described and 24 reported cases of massive rectal bleeding in intestinal tuberculosis are reviewed. Tuberculosis of the intestine, though uncommon should be considered as a cause for rectal bleeding.


Obesity in nineteen-year-old men: family size and birth order associations. The authors analyzed the prevalence of obesity by family size and birth order for a total population of over 280,000 19-year-old Dutch males, who were born between 1944 and 1947 and who were from one- to five-child families. Obesity was defined by a relative weight index, 120% or more of the standard of weight for height. Overall obesity prevalence was 1.83%; sons of manual workers were more prone to obesity than sons of non-manual workers. Individuals from one-child families (only children) were uniquely at risk for obesity, particularly in the non-manual social class. This result was similar to reported findings for childhood obesity.


Mapping of the structural gene for the second component of complement with respect to the human major histocompatibility complex. Families have been HLA typed, and allotypes of the second component of complement and properdin factor B determined. The lod score for the C2 structural gene and HLA-B from the study of 11 families and 55 informative meioses was 14.39 at maximum likelihood estimate of the recombination fraction of .02. This is related to other estimates of the distance between these two genes. The relative kinetic activities of the C2 allotypes were studied and no differences were demonstrated. No crossovers between Bf and C2 were observed.


Studies on the pathogenesis of aplastic anemia. Three assays were used to study myelopoiesis in 14 patients with aplastic anemia: (1) the soft agar colony assay for granulocyte-monocyte progenitors (CFU-c); (2) coculture of marrow from patients with normal marrows in the CFU-c assay; and (3) culture of marrow pretreated with antithymocyte globulin (ATG) in the CFU-c assay. Marrow from five patients gave low colony counts when cultured alone and suppressed colony formation by normal marrow cells in coculture. Suppressor cells may have caused the aplasia in these patients. Eight patients had low colony formation and no suppression in coculture. These patients may have absent or defective stem cells. Marrow from one patient produced normal colony formation, did not contain suppressor cells and may have a defective hematopoietic environment. Aplastic anemia thus may result from at least three different defects involving (1) the stem cells, (2) the hematopoietic environment or (3) suppressor cells.


Ovarian cancer: a solid tumor with evidence of normal cellular immune function but abnormal B cell function. Immunologic assays of B and T lymphocyte function were performed on 21 patients with epithelial ovarian cancer prior to either chemotherapy or radiotherapy. The results were compared to similar studies on 12 age-matched normal women. The total peripheral blood lymphocyte counts, proportion of E rosette positive cells, stimulation of T cells by phytohemagglutinin and concanavalin A, recall skin tests, and the ability to have a primary delayed hypersensitivity response to keyhold limpet hemocyanin did not differ between patients and controls. However, patients with ovarian cancer had statistically significant reduction in surface immunoglobulin positive cells, proliferative response to pokeweed mitogen and primary antibody response to keyhole limpet hemocyanin. In contrast to results in patients with other solid tumors, these data indicate that untreated patients with ovarian cancer have evidence of normal cellular immune function but abnormal B cell function.


Felty's syndrome without splenomegaly.

Felty's syndrome without splenomegaly. A woman with chronic rheumatoid arthritis and severe granulocytopenia but without splenic enlargement by physical examination or radionuclide scanning was studied for granulocyte-bound immunoglobulin G (IgG) and serum antigranulocyte antibodies. Prior to splenectomy 73 to 110 X 10(-14) g/cell of IgG were detected on the patient's granulocytes, a value in the range (20 to 220 X 10(-14) g) found in 16 patients with classic Felty's syndrome. Granulocyte-bound IgG in 21 patients with rheumatoid arthritis without Felty's syndrome was less than 20 X 10(-14) g. Following splenectomy, the patient had a partial correction of her peripheral granulocyte count, and granulocyte bound IgG was repeated less than 20 X 10(-14) g/cell. When paraformaldehyde-fixed granulocytes, obtained either from normal donors or from the patient after splenectomy, were incubated in the patient's serum obtained before splenectomy, more IgG was bound than with control serums from patients with rheumatoid arthritis. Similar results were obtained when serums from patients with classic Felty's syndrome were incubated with paraformaldehyde-fixed granulocytes. Thus, patients with rheumatoid arthritis without overt splenic enlargement may have pathophysiologic Felty's syndrome, and in vitro studies such as these may be used to define this process.


Obstetric cholestasis. A 14 year review. A 14 year review of obstetric cholestasis in the Women's Centre, Winnipeg, revealed 42 cases (incidence one in 1,293 deliveries). The perinatal outcome in these 42 patients was compared to that in a group of control subjects and showed a significantly higher incidence of premature labor, low-birth-weight babies, and postpartum hemorrhage. There was no particular association of intrapartum fetal distress or intrauterine growth retardation with the cases of obstetric cholestasis.


Bacterionema matruchotii ocular infections. One case of endophthalmitis and two cases of corneal ulceration, each occurring in a structurally altered eye, were associated with Bacterionema matruchotii, a gram-positive filamentous bacillus.


Immune responsiveness in patients with choroidal malignant melanoma. We studied selective in vivo and in vitro immunologic factors of 25 patients with choroidal malignant melanoma. Immune profile factors did not show consistent differences between patients with melanoma and an age-matched control population. The studies were also non-contributory in delineating variations in immunocompetence with respect to melanoma cell types. Serial immune profiles failed to identify a change when clinical evidence of metastasis developed. When tested as a group, patients with melanoma in whom metastatic disease developed during the study showed significant depression of initial mitogen-induced lymphocyte blastogenesis. This depression was noted in advance of clinically recognized metastatic disease. This group had a wide range of responses that overlapped those of control patients, thus making the usefulness of these testing factors questionable for individual prognosis or for clinical monitoring.


Autosomal recessive incomplete achromatopsia with deutan luminosity. Four patients in three different families had a form of autosomal recessive incomplete achromatopsia not previously described. The visual acuity was 6/18 to 6/60 (20/60 to 20/200) with minimal ophthalmoscopic abnormality and normal fluorescein angiogram. The photopic electroretinographic responses were present in all four patients; the fusion rate of 60 Hz was only slightly subnormal. The high-intensity scotopic response was subnormal. The patients failed color screening plates and accumulated over 400 errors with scotopic axis on the Farnsworth-Munsell 100-hue test. The Rayleigh match was abnormal, displaced toward the red primary, but with normal luminance. The photopic luminous efficiency function was similar to that of the deuteranope. Color matching revealed a trichromatic form of color vision mediated by long wavelength and short wavelength cones, and a rhodopsin receptor.


T-cell immunity to malaria in the B-cell deficient mouse. Some B-cell deficient mice drug-rescued with clindamycin HCl from otherwise lethal infections with Plasmodium yoelii resisted subsequent challenge with the same parasite despite the fact that they lacked detectable antibody to plasmodia. Parasitemias remained patent but at low levels (less than or equal to 5%) in these mice for prolonged periods of time, suggesting that some T-cell function independent of antibody formation can in part mediate immunity to malaria.


alpha 1-Acid glycoprotein, alpha 1-antitrypsin, and ceruloplasmin in human intestinal helminthiases. alpha 1-acid glycoprotein, alpha 1-antitrypsin, and ceruloplasmin levels were followed in 150 children from the rural tropics after arrival in the temperate zone. It is postulated that multiple intestinal helminthiases, especially ancylostomiasis, cause an acute phase type of reaction which is enhanced by immunization with T.A.B.-cholera vaccine.


Electron microscopic demonstration of centrifugal nerve fibers in the human optic nerve. Electron microscopic views of centrifugal nerve fibers in the optic nerve stump of a 56-year-old man are presented. These nerve fibers had survived for 16 days after removal of the corresponding eyeball and exhibited terminal swellings pointing in a distal direction and indicating axoplasmic flow towards the removed eye. The centrifugal nerves in this adult lack any evidence of attempted regeneration that has earlier been observed under similar conditions in the optic nerve stump of a child.


Ketamine-induced ultrastructural changes in the retina. The author studied the retinal changes induced by ketamine in animal experiments. Ultrastructural changes were observed in the inner segment of the photoreceptors, in the three nuclear layers, and in the nerve fiber layer following ketamine monoanesthesia of 60 min duration. A pronounced destruction of the Müller's cells nourishing the nervous elements was seen. Three days after the anesthesia, remarkable regression of the neuronal changes and extreme accumulation of glycogen in the Müller's cells occurred. These phenomena, as well as some other ophthalmological side effects, were explained with the development of relative retinal hypoxia due to the increased oxygen metabolism which was caused by the ketamine anesthesia.


[X-linked night-blindness: clinical and electrophysiological investigations including de-ERG in two families (author's transl)]. Patients from two families with X-linked recessive nyctalopia and myopia were investigated. The functional tests included clinical examinations (visual acuity, color sense, visual fields, dark adaptation) and electrophysiological examinations (ac coupled ERG, dc-coupled ERG, EOG). The dc-coupled ERG registrations were done without general anesthesia. In one case, a comparison with results obtained in 1967 was possible. There was no evidence of increase in functional impairment. On the basis of the electrophysiological results, the nature and localization of the defect causing nyctalopia are discussed. The postreceptoral retinal structures appear not to be involved exclusively.


Cyclovergence: the motor response to cyclodisparity. Static photographic evidence of the occurrence of cyclovergence is presented that supports and extends the result of Crone and Everhard-Halm (1975). Wide-angle complex targets were a necessary condition; simple horizontal line targets were insufficient. Our asymmetrical disparity targets supported in part the conformance of cyclovergence to Hering's Law but raised questions relating to the computational process that also acts to remove cyclodisparity and permits cyclofusion. Saturation and hysteresis nonlinearities were observed.


[Behavior of fluorescein dye in the vascularized cornea of the animal eye after local application of certain drugs (author's transl)]. In pigmented rabbits we investigated the much-used drugs pilocarpine, atropine, and tropicamide (Mydriaticum, Roche) with regard to their possible influence on the permeability of newly formed corneal vessels. Sodium fluorescein was chosen as test substance. Corneal vessels were produced by introcorneal injection of 0.1 N NaOH. Their development required 2--3 weeks and their growth about 4--6 weeks. A 2-week period of stability followed and was used for the local application of the above drugs. An evident influence on the diffusion of fluorescein could not be ascertained. Tropicamide induced a narrowing of the dye column in the corneal vessels. This phenomenon may be due to a narrowing of supplying vessels. In all cases, dye diffusion took place especially at the peripheral loops of the corneal vessels.


Cathepsin B and collagenolytic cathepsin in the aqueous humor of patients with Behçet's disease. Cathepsin B and collagenolytic cathepsin activities were studied biochemically in human aqueous humor. The enzyme activities were found to be significantly high in the aqueous humor of the patients with Behçet's disease, but not detectable in those with senile cataract, retinoblastoma, and maxillar carcinoma. These data suggest that cathepsin B and collagenolytic cathepsin have a certain role in the inflammatory collagenolytic process of Behçet's disease.


[Studies on pigmented surface wrinkling retinopathy by scanning electron microscopy (author's transl)]. The light- and scanning electron microscopic appearance of 3 areas of pigmented epiretinal fibroplasia (pucker) are described in an eye removed following detachment surgery. The centre of each area of pucker consists of a fibroglial sheet covered by retinal pigment epithelium. The surface morphology of these cells resembles typical or slightly degenerated epithelium. Extensive areas of these pigment epithelial sheets were pigmentfree. There was no evidence that the pigment epithelial sheets exerted either direct or indirect traction on the inner surface of the retina. The origin of these cells and their role in the formation of retinal wrinkling is discussed.


[Colour vision in squint amblyopia (author's transl)]. Colour vision in squint amblyopia depends on the fixation modus. In eyes with foveolar or unsteady foveolar from fixation the 3 primary colour vision mechanisms (CVMs) gave normal foveolar CVM patterns. The absolute spectral retinal sensitivity was somewhat, but not significantly lowered. The spectral sensitivity for hue discrimination was either normal, or slightly reduced in the short wavelength side, or slightly reduced over the whole visible spectrum. The spectral sensitivity for saturation discrimination showed normal curves. -- In amblyopic eyes with parafoveal to perifoveal fixation mode the absolute spectral retinal sensitivity is lowered for about 0.45--0.60 log units in comparison to an approximately corresponding excentric retinal area in a normal eye. In eyes with parafoveolar to perifoveal fixation mode measurements of CVMs and of hue discrimination gave better results than could be expected with regard to the position of the fixating area as determined by visuscope. The values correspond to those obtained in retinal areas at least as close to the foveola as the amblyopic fixation point, but usually of an even more central position. The sensitivity for saturation discrimination showed no significant disturbance.


[The influence of vigilance on DC response in human visual evoked potential (author's transl)]. Visual evoked cortical potentials elicited by long-lasting stimuli of red light were examined in eight subjects under different conditions of vigilance. The DC components of the evoked potentials were compared with the delta and theta activity (0-7.5 Hz) of the EEG by means of frequency power spectra. The results are: 1) A proportional relationship exists between the amplitude of the negative DC component of the evoked potential and the theta and delta activity in the EEG. 2) Under conditions of low vigilance the negative DC potential does not return immediately to the baseline after the off-effect. Instead it may reach a second peak. 3) Under conditions of high vigilance, the DC potential may reverse its polarity. Its return to the baseline following the off-effect is immediate. 4) No dependence of the cortical DC potential on the intensity of the light stimulus could be demonstrated. 5) Since the negative potential outlasts the visual stimulus and could be recorded at the occiput and the vertex, it may be regarded as a nonspecific arousal reaction. Furthermore, since the positive DC potential can only be recorded at the occiput, it is regarded as a specific stimulus-correlated response.


[Visual field response to hypotension following oculopression (author's transl)]. The authors studied the visual fields in 100 healthy persons of different ages before and 10 min after oculopression. They found a depression of the I/2 isopter mostly in the nasal lower quarter of the visual field in persons over 60 years old, due to a disturbed or diminished vascular compensation of bulbus compression. They consider that oculopression might have clinical importance as an indirect provocation test of the cellular blood circulatory system.


Micropsia and visual acuity in macular edema. A study of the neuro-retinal basis of visual acuity. Relative micropsia was measured by a matching technique in patients with unilateral, benign, macular edema. Quantitative assessment of foveolar micropsia to be a sensitive indicator of receptor displacement in this disorder, and may be a useful tool both for diagnosing and for monitoring macular edema. Parallel measurements of grating acuity showed a close proportionality between acuity and micropsia parameters. This result validates a new quantitative theory for the neuro-retinal basis of visual acuity. The theory allows prediction of the proportion of working visual neurons in patients with impaired acuity due to diseases that produce a diffuse loss, or disconnection, of macular cones. Our results indicate that so-called normal visual acuity (1.0 or 20/20) requires no more than 44% of the normal quantity of fovelar, neuro-retinal channels.


Comparison of visual function studies in two cases of senile macular degeneration. In this paper two relatively early cases of senile macular degeneration are compared by making use of a number of tests of visual function, some relatively new, coupled with observation of the fundus and analysis by fluorescein angiography. The functional tests include visual acuity, the sustainedlike and transientlike functions which are believed to test inner retinal receptive field properties and to have origin in the inner and outer plexiform layers, the Stiles-Crawford function which reflects the directional sensitivity and orientation of photoreceptors, and increment threshold curves. In one case there was evidence of inner retinal involvement at the time the tests were conducted, but, because the Stiles-Crawford function remained essentially normal, it is assumed that the receptors were not disturbed relative to their orientation. In this case (as in many others), the zone or area exhibiting functional change does not necessarily match the area exhibiting anatomical change as observed by examination of the fundus, fundus photography, and fluorescein angiography. In the second patient there is evidence of both anomalous inner retinal function and disturbance in receptor alignment. The later suggests disorientation of the receptor bed. These findings correlated with the fundus observation and fluorescein angiographic evidence of a leak, resulting in the presence of serous fluid beneath the neurosensory retina. With resolution of this fluid there was a return of the functional tests toward normal. At this time, it is not possible to determine whether, in two cases, the functional changes are proceeding on a parallel course, but are at different stages, or whether they are the expression of somewhat different anomalies.


The central ocular hypotensive effect of clonidine. Clonidine was administered into the left vertebral artery of anesthetized cats. A dose-response curve of the lowering effect on intraocular pressure (IOP) has been made and compared with the dose-response cure obtained after intravenous administration. A more pronounced decrease in IOP after the first route of administration became evident. The effect is not secondary to a stronger reduction of blood pressure by centrally injected clonidine. Distribution experiments with 14C-clonidine revealed no direct connection between the vertebral arteries and the blood supply of the eye. For 2 h the concentrations in the eye are somewhat lower than after intravenous administration. Therefore, the IOP-lowering effect is not due to a direct influence of clonidine on the eye. It is submitted that the clonidine-induced reduction in IOP is at least in part due to a central mechanism, in which the stimulation of central alpha-adrenoceptors and adrenergic neurons may be involved. The relevance of this hypothesis with regard to a possible central regulation of IOP is discussed.


[Haemodynamic effects of combined dopamine and nitroprusside therapy early after open heart operations (author's transl)]. In 12 patients with moderate low-output-syndrome following aortocoronary bypass grafting, the pump function of the left ventricle was improved by sodium nitroprusside (SNP) and dopamine. The cardiac index (CI) on termination of cardio-pulmonary bypass was 2.2 +/- 0.2 1/min.m2 and the pulmonary capillary wedge pressure (PCWP) 20 +/- 3 mm Hg. Folowing infusion of SNP the Cl reached 2.4 +/- 0.2 l/min.m2 (p less than 0.05) and the PCWP was reduced to 13 +/- 3 mm Hg (p less than 0.01). After transfusion of blood the PCWP increased to 18 +/- 2 mm Hg (p less than 0.01), and the CI increased to 2.8 +/- 0.2 l/min.m2 (p less than 0.05). After administration of dopamine the CI was further improved to 3.3 l/min.m2, the PCWP remained constant. The combined therapy with dopamine and SNP is a rational concept to improve the function of the heart in failure following open heart surgery.


[Extrarenal effects of potassium-canrenoate. Haemodynamic investigations during neuroleptanalgesia in cardiosurgical patients (author's transl)]. Direct cardiac and vascular effects of the antikaliuretic diuretic potassium-canrenoate were measured in cardio-surgical patients during extracorporal circulation and immediatly after operations, each time in neuroleptanalgesia. During "steady state" extracorporeal circulation (aorta cross-clamped, constant flow rate of heart-lung-machine, constant hypothermia), in 13 patients no significant influence on peripheral circulation was found after i.v.-injection of 800 mg potassium-canrenoate. Neither arterial perfusion pressure (representing an arterial vascular reaction) nor changes in oxygenator-volume (indicating venous vasodilation or contraction) demonstrated significant differences in comparison to a control group. After cardiac surgery haemodynamic measurements were performed for a period of 60 minutes in 10 patients given 800 mg potassium-canrenoate. In comparison with a control group (n = 6), no significant differences in arterial pressure, heart rate, cardiac index and pulmonary arterial pressure were found. Left ventricular measurements, using a catheter tip manometer, revealed no direct positive inotropic effect of a single i.v.-injection of potassium-canrenoate. In acute myocardial failure during anaesthesia or in "low cardiac ouptut" following open heart surgery no improvement in myocardial contractility is obtained by i.v.-application of potassium-canrenoate; at the present there seems no alternative to other positive inotropic agents such as calcium, glucagon, dopamine, orciprenaline and epinephrine.


Evaluation of B-lymphocyte levels and functions in gnotobiotic dogs. Quantitative and qualitative aspects of B-lymphocyte functions in gnotobiotic dogs and conventional dogs were determined. Using 3 different methods to identify B-cells by surface markers and 3 different methods to measure immunoglobulins (eg, serum electorphoresis, immunoelectrophoresis, and radial immunodiffusion), it was determined that gnotobiotic dogs were B-cell deficient. Related studies, however, indicate that the capacity to develop humoral immune responses was unimpaired. It is presumed that lack of immunogenic stimulation within the gnotobiotic isolation units accounts for this observation.


High-dose methotrexate and leucovorin rescue in dogs with osteogenic sarcoma. Five dogs with ostoegenic sarcoma were treated by surgical removal of the primary tumor and by adjuvant chemotherapy. Methotrexate at dosages of 3 to 6 g/m2 was used with leucovorin rescue. All dogs tolerated E g of methotrexate/m2 of body surface, but granulocytopenia precluded escalation beyond this dosage in 4 dogs. The rate and time of appearance of pulmonary metastases were not altered by treatment, with all dogs developing metastases at a median time of 4 months after amputation.


Rheumatoid meningitis: a localized immune process. Rheumatoid pachymeningitis is a rare complication of rheumatoid arthritis. This disease was confined to the dura and pia-arachnoid of the lumbar cord in our patient. Her neurologic deficits responded to surgical decompression and corticosteroid therapy. Radiologic evidence and the differences in cell count, protein, and glucose content between lumbar and cisternal cerebrospinal fluid indicate that rheumatoid pachymeningitis can be localized to a discrete region of the central nervous system. Elevated immunoglobulins, IgM and IgG rheumatoid factors, low molecular weight IgM, and immune complexes were found in the cerebrospinal fluid and implicate an immune reaction in the pathogenesis of this disease, which is probably similar to inflammatory processes involving other organs in rheumatoid arthritis.


[Coronary by-pass operations in diabetic and non-diabetic patients with angina. Results of 102 coronary arteriographies (author's transl)]. The results of coronary arteriography were compared in 102 patients (55 non-diabetics and 47 diabetics) with angina. The lesions noted an arteriography were more severe in the diabetic patients: more frequent stenosis in the common trunk and three branches, and present in greater numbers (more than 4 in more than a half of the patients), with only a moderate proximal bed in 65% of the cases. By-pass operations can only be performed, therefore, in 32% of these patients as against 54% for the non-diabetic anginal patients. The operative risk also appears to be increased (1 death and 6 complications in 10 by-pass operations). It was also demonstrated that with similar lesions of the common trunk, the diabetics have radiological signs of a greater incidence of cardiomegaly and generalized hypokinesia of the left ventricle than non-diabetics. By-pass operations are impossible in about 85% of patients because of ischemic signs or evidence of necrosis in the ECG recordings of diabetic patients with angina.


Intravenous effects of pimaricin on mycotic endophthalmitis. Rabbits weighing 2 to 3 kg with induced Candida endophthalmitis in the left eye were given 5 mg/kg and 10 mg/kg pimaricin intravenously. In the course of investigation, no significant level of pimaricin was found in the vitreous of those animals receiving 5 to 10 mg/kg pimaricin intravenously, and only 3 microgram/ml aqueous was found after chronic therapy for 1 to 3 weeks. No ocular or retinotoxicity was noted, although toxicity was inherent in the liver, kidney, and endocrine glands. From these studies, it is concluded that intravenous therapy alone is not sufficient for treatment of fungal endophthalmitis due to high toxicity and inadequate ocular drug levels.


[Vestibular toxicity of gentamycin: value of the galvanic test (author's transl)]. A total of 6 cases of bilateral vestibular areflexia due to Gentamycin are reported. Vestibular destruction was associated with deafness in only 3 of the patients. Two patients had no signs of renal insufficiency. Galvanic vestibular exploration showed complete and bilateral lack of excitability in 3 out of 4 cases, which could be due to the co-existence of nerve or nuclei lesions. In one case, galvanic excitability was within normal limits, and severe equilibrium problems presisted. The presence of an asymmetry on galvanic examination could be an unfavourable prognostic sign in vestibular toxicity due to Gentamycin.


[Bilateral deafness due to the local use of framycetin (author's transl)]. A case is reported of total bilateral cochleo-vestibular destruction following instillation of Framycetin into the middle ear, under pressure, through a transtympanic drain. Toxicity of Framycetin after local use is exceptional and only one case, reported by Ransome, was found in the published literature. The interest of this observation is that, by using puncture of the foot of the stapes, it was possible to find Framycetin in the perilymphatic liquid three weeks after the injection of the product.


Screening for cystic fibrosis in the newborn by meconium analysis. During a 4-year routine screening programme for cystic fibrosis (CF) 15 464 specimens were examined for raised meconium albumin levels by a test strip method and by electroimmunoassay. The incidence of false-positive results was about 5 per 1000 specimens in either test. This could be reduced by 90% by determining the ratio of albumin : alpha-1-trypsin inhibitor (a ratio below 2.0 being considered as a negative result), and it could be reduced to zero by determining the ratio in subsequent faecal specimens. Three of 12 meconium specimens from infants with proved CF gave false-negative results in all 3 tests. The other 9 specimens had greater than 100 mg albumin/g dry weight and albumin: alpha-1-trypsin inhibitor ratios of greater than 3.0; in subsequent faecal specimens the ratios were over 4.0. 176 meconium specimens from elsewhere in the UK were examined and these included 23 from infants who were subsequently proved to have CF. Six of these 23 CF specimens gave false-negative results, the other 17 being strongly positive. The origins of meconium serum protein suggest that infants with CF in whom meconium gives false-negative results have normal pancreatic functions at birth. The specificity of current meconium tests therefore cannot be improved as they depend on pancreatic dysfunction.


Middle ear function in rheumatoid arthritis. Using an otoadmittance meter the function of the middle ear was compared in 38 patients with rheumatoid arthritis (RA) and 30 matched controls with non-articular rheumatism. Patients with pre-existing ear disease were excluded from the study. No subjects in either group showed hearing loss on pure tone audiometry, but otoadmittance abnormalities were recorded in 16 of the RA (42%) and in 2 of the control groups (7%). The pattern of abnormality was similar in each case and indicated an increased laxity of the conducting system. The reason for this unexpected finding is unknown. There were no significant differences between the RA patients with normal or abnormal recordings as regards clinical or laboratory features or treatment.


Intra-articular and circulating immune complexes and antiglobulins (IgG and IgM) in rheumatoid arthritis; correlation with clinical features. Solid phase radioimmunometric methods have been used to assay immune complexes and IgG and IgM antiglobulins in paired samples of synovial fluid and serum from patients with rheumatoid arthritis (RA) or osteoarthrosis. Over 60% of RA patients had some increase in complexes in their sera, while nearly 90% had synovial fluid complexes. Moreover, the levels of complexes within the joint were much higher than in the serum. Both IgG and IgM antiglobulins were raised in most RA patients. The levels of IgG antiglobulins--and to a less extent IgM antiglobulins--were nearly always higher in synovial fluid than in the corresponding serum sample.A strong correlation was found between the levels of immune complex and IgG antiglobulin. A marked association was seen between the presence of subcutaneous nodules and increased IgG antiglobulins.


Clinical significance of antibodies to ribonucleoprotein. Antibodies to ribonucleoprotein (RNP) were detected by an immunofluorescence technique based on the sensitivity of speckled antinuclear antibodies to ribonuclease. These antibodies were found to identify a group of patients with a consistent set of clinical features, especially arthritis, swollen hands, Raynaud's phenomenon, and myositis. The presence of anti-RNP antibodies in sera from patients with polymyositis, systemic lupus erythematosus, and systemic sclerosis was also associated with these clinical features. Other studies of the clinical significance of these antibodies support the concept that they appear to identify a group of patients with a distinct clinical condition.


Studies on cell surface antigens of mouse leukemic and normal lymphocytes. IV. Functional studies on mouse T lymphocyte subpopulations. B. Lyt phenotype of cytotoxic T lymphocytes and their precursors in B6-Lyt-1.1 mice. Lyt phenotype of in vitro generated alloreactive cytotoxic T lymphocytes (CTL) and their precursors in B6-Lyt-1.1 (Thy-1.2, Lyt-1.1, Lyt-2.2) congenic strain of mice was studied. The generation of CTL in vitro was completely abrogated by pretreatment of responder cells with antisera to Thy-1.2, Lyt-1.1 and Lyt-2.2 antigens and complement. Mixing of anti-Lyt-1.1-pretreated cells with anti-Lyt-2.2-pretreated cells did not restore CTL generation indicating that both Lyt antigens are expressed on the same precursor cell population. The effect of anti-Lyt sera was specific because the generation of CTL was prevented only when cells from strains possessing appropriate Lyt alleles were pretreated. CTL were eliminated by lysis with anti-Thy-1.2 serum and strongly reduced by anti-Lyt-1.1 and anti-Lyt. 2.2 sera. Nevertheless, a small but significant proportion of CTL was insensitive to lysis with anti-Lyt sera. These data indicate that a phenotype of precursor cells and of majority of CTL is Thy-1.2+ Lyt-1.1+ Lyt-2.2+.


Preliminary testing of DRw antigens in a Polish population. B lymphocyte subpopulations taken from 89 individuals were investigated with 180 sera from the seventh Histocompatibility Workshop. The results obtained served in determining the frequency of 8 DRw antigens in a tested population sample. Their incidence was comparable to the frequencies determined during the Workshop for the reference group of European Caucasoids.


HLA and antinuclear antibody incidence in asbestos workers. The incidence of antinuclear antibodies (ANA) in asbestos textile workers was compared with the results of HLA typing. HLA B8 antigen was more frequent in the ANA-positive group as compared to the ANA-negative group. The relative risk of this associati-n is 2.77 (p less than 0.02) without correction for the number antigens tested. A decrease in frequency of HLA A10 in workers with ANA was also found. The results suggest that the development of ANA under asbestos hazard may depend on inherited predisposition of which HLA B8 is a marker.


Bursa-independent origin of Fc IgG receptor-bearing lymphocytes in chickens. On the basis of performed studies the following observations indicate that there is a bursa-independent origin of lymphocytes with Fc IgG receptors: (a) the first appearance of Fc positive cells is in fetal liver and bone marrow, (b) a relative low percentage of Fc receptor cells, as compared to B cells, occurs in the bursa during the embryonic and post-hatching period, (c) a far lower percentage of Fc positive cells than B cells is found in the spleen, (d) a normal level of Fc positive cells occurs in bursectomized birds, (e) a majority of these cells do not possess thymic or bursa antigen or surface immunoglobulin.


Subpopulations of T and B lymphocytes in peripheral blood and lymphocytes reactivity to non-specific mitogens (PHA, Con A, PWM) in in vitro cultures in patients suffering from in vitro cultures in patients suffering from glomerulonephritis. Studies were performed on 79 subjects, out of which 32 belonged to the control group and 47 suffered from glomerulonephritis. The number of T and B lymphocytes in peripheral blood was determined using the technique of E, EA and EAC-rosette tests. Also, the lymphocyte blast response to non-specific mitogens (PHA, Con A, PWM) was established in vitro. Patients suffering from acute proliferative glomerulonephritis, as compared to the control group, displayed a statistically significant increase of lymphocytes with the receptor for complement (EAC-rosettes). Their reactivity to all three mitogens did not differ from the values obtained in the control group. In patients suffering from chronic glomerulonephritis (proliferative, membranous-proliferative, membranous), shiftings in the contents of the peripheral blood lymphocytes pools were of opposite directions, i.e., statistically significant in comparison with the control group. Also an increase in the absolute number of T lymphocytes (E-rosettes) was observed. Generally speaking, the values of blast transformations after mitogen stimulations were smaller in patients suffering from chronic than in those suffering from acute glomerulonephritis. In 1/3 of them, the decrease of blast response to one of the three mitogens was detected. The decrease exceeded the lower limit of values of healthy subjects, and most often, it was connected with Con A stimulation.


Attempts to evaluate the role of the third complement component (C3) and complement receptor lymphocytes (CRL"+") in the induction of the humoral immune response. It has been shown that spleen and bone marrow complement receptor lymphocytes (CRL"+") are responsible for T-dependent anti-SRBC response. This has been shown by comparison of the T-dependent anti-SRBC and T-independent anti-SIII response in irradiated mice repopulated with normal or CRL depleted spleen cell populations. Unseparated spleen cells obtained from animals immunized 48 h before with SRBC, and CRL depleted cell population from animals receiving T-independent antigens (levan, SIII) were shown to be predominantly stimulated when uptake of isotope labelled leucine or tymidine was studied. It was also shown that triggering of enhanced antibody production by T cell derived signal generated during GvH reaction is C3 dependent.


Lymphocyte B population in calves under different breeding conditions. Using the EAC rosette test 176 lowland black white (lbw) and lowland red white (lrw), 0-130 day-old calves were examined to determine the number of lymphocytes B. The calves came from 2 farms with different industrial breeding technology. Farm A was characterized by a considerable mortality of the animals due to diseases typical for the neonatal period, whereas in farm B no deaths were noted. As the result of examinations it has been found that calves from farm A showed an appreciably higher incidence of lymphopenia with concomitant higher maximal numbers of EAC-rosettes-forming-lymphocytes.


In vitro cytotoxic effect of lymphocytes and their extracts in inflammatory bowel diseases. I. From the sera of 20 patients with ulcerative colitis (U.C.) 10 patients with Crohn's Disease (C.D.) and 10 volunteers, lymphocytes were isolated and extracts of whole lymphocytes (T+B+K) and pure T lymphocytes were prepared. Whole lymphocyte extracts were further fractionated into fraction A containing mainly antibody and fraction B containing mainly membrane-bound receptors. The ability of various lymphocytes and their extracts to lyse allogeneic colonic epithelial cells in vitro was tested with and without the addition of 50 microgram of Common antigen (C.A.) used as a blocking agent. The percentage of cells lysed by whole lymphocytes correlated well with the severity of symptoms of the patients with U.C. Pure T lymphocytes were cytotoxic only in C.D. but not in U.C. Isolated extracts fractions A and B were not cytotoxic in active U.C. except when tested in combination. The addition of the Kunin antigen blocked the effect of lymphocytes from patients with active U.C. The results indicate differences in the mechanism of immunological activity of lymphocytes in U.C. and C.D. and show a direct relation of B lymphocytes and K cells to the cytotoxicity of U.C.


Properties of antisera against lymphocytes of nude mice. This paper reports results of a study on the activity of rabbit antisera against nu/nu Balb/c lymphocytes in vivo and in vitro. It was found that ALS against nu/nu lymph node cells suppressed the alloantigen reaction and the sRFC or PFC formation for T-dependent (SRBC) and T-independent (LPS) antigens. ALS against nu/nu spleen cells affected only the sRFC and PFC for T-independent antigen. The former serum exhibited a high cytotoxicity for the suspensions enriched or depleted in B cells while the latter one was more cytotoxic for the suspension enriched in B cells. It indicates that ALS anti nu/nu spleen cells is specific for B lymphocytes and ALS anti nu/nu lymph node cells is directed not only to B cells but also to a subpopulation of T lymphocytes. It suggests the existence of a subpopulation of T lymphocytes in nu/nu lymph node cells.


The effect of horse-anti-rabbit thymocyte antiserum (ATS) on draining lymph node cells in rabbit. I. Number of cells coated with anti-lymphocytic antibodies. The percentage of popliteal lymph node lymphocytes coated with anti-lymphocytic antibodies was defined by the immunofluorescent test. It was shown, that 4 hrs after ATS injection, 18-40% of lymphocytes in draining lymph node were coated with antibodies and gave positive fluorescence with rabbit anti-horse IgG FITC. There was no cells with antibodies in contralateral lymph node.


The effect of varying SRBC/lymphocyte ratio on T cell rosette formation. To determine the effect of varying the SRBC/lymphocyte ratio on rosette formation, rosettes were formed at SRBC/lymphocyte ratios ranging from 10 to 200. To assess the significance of the time of incubation, duplicate samples were mixed at various SRBC to lymphocyte ratios and the percentage of rosette-forming lymphocytes was determined immediately or after an 1-hour incubation at 4 degrees C. The results of five experiments revealed the highly statistically significant difference between the percentage of rosette-forming cells in tests performed with (higher number of RFC) and without (lower number of RFC) incubation, in all SRBC/lymphocyte ratios. On the other hand, ratio of SRBC to lymphocytes influenced significantly the results obtained in both types of tests, this effect was more pronounced in test performed with 1-hour incubation. Optimal SRBC/lymphocyte ratios for both tests were 100:1 (31% RFC without incubation and 53.4% of RFC after 1-hour incubation.


Studies on the influence of thiols on lymphocytes (T-type lymphocytes) function. Changes of the oxidation/reduction potential of the coupled -SH/SS low molecular sulfhydryl system in rat lymphocytes were determined after incubation of cells with D-penicillamine, cysteine and cysteine hydrazide, in concentration of thiols which did not disturb the response of the cells to phytohemagglutinin (PHA). Considerable increase of the -SH content in lymphocytes was observed after treatment of the cells with cysteine and cysteine hydrazide. Our findings suggest that the biological effect of thiols used in optimal concentrations and conditions might be coupled with the disturbance of the -SH/SS oxidation/reduction system in cells.


Studies on the influence of thiols on lymphocytes (T-type lymphocytes) functions. We described changes in nonprotein sulfhydryl content and in intracellular concentration of cysteine (unbound form) in lymphocytes incubated with cysteine, cysteine hydrazide and D-penicillamine (dimethy lcysteine) in concentrations which do not alter the viability of the cells. Essential differences between the action of cysteine and cysteine hydrazide on one hand, and D-penicillamine on the other, can be observed. The formers cause the argumentation in nonprotein thiols content in lymphocytes, whereas D-penicillamine in a similar concentration does hardly alters the intracellular redox -SH/SS potential of nonprotein thiols within the lymphocytes.


Fractionation of human T lymphocytes on the basis of their high, medium and low SRBC-rosette-forming affinity: efficiency of the method. Under optimal saturating conditions at SRBC/lymphocyte ratio 100:1 26 +/- 1.2% of human peripheral blood lymphocytes isolated from defibrinated blood form rosettes without incubation, 48 +/- 1.8% after 1-hour, 68 +/- 1.7% after 2 hours incubation at 4 degrees C. According to this, human peripheral T lymphocytes may be subdivided into at least three fractions on the basis of their affinity to SRBC. We called these fractions AFRC (no incubation), C1 RFC (1-hour incubation in cold after removing ARFC fraction) and C2RFC (2-hour incubation in cold after removing ARFC and C1RFC fractions). All the three fractions may be separated by repeated rosetting followed by Ficoll-Uropoculine gradient centrifugation. The purity and viability of T lymphocytes yielded from particular fractions was high. Effective yield of lymphocytes varied between the particular fractions ranging between 100% (for AFRC) and 30% (for C2RFC).


Suppression of anti-hapten (TNP) antibody response by suppressor T cells and their product. The role of macrophages. The effect of the lymphocytes from picryl sulfonic acid treatment animals on primary and secondary humoral immune response to TNP hapten was investigated. These cells known to inhibit contract sensitivity reactions were also able to depress primary IgM response. When peritoneal exudate cells from normal mice incubated in suppressor supernatant were transferred into primed mice the suppression of IgM but no IgM secondary response was observed. In contrast peritoneal exudate cells incubated in control supernatant augmented IgM but didn't affect IgG response. It is postulated that normal peritoneal exudate cells (presumably macrophages) can stimulate IgM response. This enhancing activity could be partially blocked by soluble suppressor factor.


Monocyte changes in cancer patients and their role in mitogen induced lymphocyte responses. Monocyte Fc receptor expression and monocyte-mediated antibody dependent cell cytotoxicity (ADCC) was studied in a group of patients with stomach and colorectal carcinoma. Is was found that FC receptor expression and ADCC was increased in patients as compared to control subjects. These differences were more evident after trypsin pretreatment of monocytes. There was an inverse correlation between these changes and lymphocyte response to PHA. The role of monocyte functional changes in determining the magnitude of patients' lymphocyte response is discussed.


Investigations on immunological and pharmacological activities of thymus factor X/TFX. Immunological activity of TFX was investigated on mice employing the imuran (rosette) and hydrocortisone (cytotoxic) tests. Pharmacological activity in the acute and chronic experiments was also evaluated.


Colony stimulating factor (CSF) activity in human and murine sera. Substances with CSF activity were studied in human and murine sera. Gel filtration of the sera on Sephadex G-200 showed that fractions with molecular weight of 14,000 and 6000 D were active in the CSF test. When mice were stimulated with endotoxin, CSF activity of both fractions was twice as high as in control animals, and CSF activity was found also in a protein peak with the molecular weight of 300,000 D. The fractions with CSF activity were sensitive to pepsin.


Effect of thiosulfate on the immune response in mice, in vitro. It was found that intravenous application of thiosulfate increased non-specifically immunoglobulin concentration in mice sera. Thiosulfate stimulated the immune response to T-dependent antigens.


Serum antitrypsin activity and alpha1 antitrypsin level in atopic bronchial asthma. The aim of our investigations was to evaluate the behavior of the important proteolitic inhibitor--serum alpha1 antitrypsin in patients with atopic and non-atopic bronchial asthma. The inhibitor concentration was determined by means of the immunodiffusion method, and antitrypsin activity was evaluated using the synthetic substrate BAPNA. The investigations were carried out on 53 patients with bronchial asthma and on 13 healthy persons. It was found that in some patients with atopic asthma alpha1 antitrypsin level and antitrypsin activity were very low but this did not lower significantly the mean value of the whole group. The results presented suggest that a relative alpha1 antitrypsin deficiency, at least in some patients, can be considered as being one of the pathogenetic factors in atopic asthma. In addition, determination of serum antitrypsin activity may be of practical significance in differential diagnosis of bronchial spastic reactions of bacterial and allergic origins.


Activity of serum inhibitory proteases in bronchial secretions from children with various chronic non-specific respiratory diseases. In a group of 223 children with various chronic, non-specific respiratory diseases, the levels of serum inhibitory proteolytic enzymes in bronchial secretions was measured. Activity of inhibitory proteolytic enzymes was analyzed according to the nature of bronchial lesions observed at bronchoscopy and character and cellular composition of bronchial secretion. Statistically significant increase of the mean inhibitory value in comparison to values in the control group, was found in children with recurrent bronchitis (a-1-AT), cystic fibrosis (a-1-AT and a-1-X), chronic bronchitis (a-1-X), bronchiectases (a-1-X) and in children with obstructive bronchitis (a-2-M).


Experimental allergic encephalomyelitis in chickens. Experimental allergic encephalomyelitis (EAE) in chickens of the inbred lines IC, CB, WB and (CBxIC)F1 hybrids was investigated. The IC line and (CBxIC)F1 hybrids gave the best reactions. In bursectomized chickens only slight changes in brain were observed. The intensity of EAE in thymectomized chickens was highly suppressed. Using the anti-T and anti-B sera it was shown that, the percentage of EAE of B lymphocytes was increased. Among the used several immunosuppressive drugs which generally decreased inflammatory reactions in brain the best results were observed with azathioprine and actinomycin D. Moreover, cyclophosphamide gave the worse results which was shown in the same experiments. The aim of our experiments was to define the role of thymus and bursa of Fabricius and peripheral B and T lymphocytes in the course of EAE. Moreover, the effect of immunosuppressive drugs on EAE was studied.


Cell-mediated immunity (CMI) in psoriasis. Patients with psoriasis were found to have less intensive experimental DNCB sensitization and decreased lymphocyte response to nonspecific mitogens, PHA, Con A, and PWM. E rosette formation was defective only in active psoriasis, in contrast to normal T and B cell counts. A reduction in DNCB hypersensitivity development and the percentage of E rosette forming lymphocytes were related to disease activity, but not to extention of skin lesions. The defect of E rosette function appeared to be transitional and completely disappeared in the remission. Abnormalities in CMI in psoriasis were found to be related at least partially to the existence in patients sera of a factor inhibiting normal T lymphocyte function. The study provides no evidence for the presence of primary CMI defect in psoriasis.


Antibodies against extractable nuclear antigens (ENA) in systemic scleroderma. Antibodies against nuclear ribonucleoprotein (RNP) were found in 5 of 63 cases of systemic scleroderma, whereas they were present in all but one case of mixed connective tissue disease and in 15 of 67 cases of systemic lupus erythematosus. In all RNP positive cases of systemic scleroderma there were some features of other collagen diseases, and their course was relatively more benign. Studies of RNP antibodies in systemic scleroderma may be of importance for treatment and prognosis.


Synthetic antigens. Antigen-binding cells to interpolymer of styrene and maleic acid (PSM) and sheep red blood cells in mice and rats immunized with PSM. To study the mechanism of the immune response, a new type of synthetic antigen: interpolymer of styrene and maleic acid (PSM) was introduced in our laboratory. In our previous papers it was proved that PSM is immunogenic and antigenic in various animals PSM had also adjuvant properties.


Mixed connective tissue disease (MCTD)--its immunological characteristics. The concept of the MCDT is controversial; it is still not settled whether it is nosological entity, or a variety of SLE, or a special variety of scleroderma. From the practical point of view the authors consider it important to perform tests for RNA antibodies whenever the characteristics of different collagenoses coexist. Detection of the antibodies is relevant both to the prognosis and the choice of treatment.


Immunological characteristics of lymphocytes in synovial fluid and peripheral blood in patients with rheumatoid arthritis. The investigation has been carried out on 30 patients with rheumatoid arthritis. Rosettes (E, EA, EAC) technique and immunofluorescence test were used to detect the surface markers of lymphocytes. Cytotoxic activity of T and K cells in vitro was established. It has been proved that cells occurred to a larger extend in synovial fluid than in the peripheral blood. B cells and lymphocytes with Fc receptors were only a few in synovial fluid. The percentage ofFc receptors bearing cells was higher in the peripheral blood of patients with rheumatoid arthritis than that in peripheral blood of the control group. Cytotoxic activity of K-cell was low in synovial fluid. PHA-cell mediated cytotoxicity was low in peripheral blood as well as in synovial fluid of patients with rheumatoid arthritis.


The monitoring of lymphocyte subpopulations in non Hodgkin lymphoma patients during chemotherapy. Numerous examinations of the changes in B, T, null subpopulations were systematically carried out in 20 non Hodgkin lymphoma patients 8, 24, 48 hours after the therapy onset and subsequently at intervals of a few days during and after each chemotherapy cycle (COP, Knospe). T cells were evaluated by examining the receptor for neuraminidase pretreated sheep erythrocytes (nE), B lymphocytes by detecting surface immunoglobulins (SmIg) with normal and Fc deprived anti Fab2 globulin, moreover receptors for mouse erythrocytes (Em) and for C3 (EAC) were examined. A characteristic rise of the dominating subpopulation was observed during the first phase of the drug application which, most probably, was due to an expulsion of the pathological cells from involved lymphatic organs to the blood. On the basis of our clinical observations a conclusion has been drown, that this type of monitoring possibly renders a maximal effective treatment, enables the control of the accompanying immunosuppression and offers an additional criterion of the remission.


The study of T-lymphocytes, granulocyte's phagocytic activity, and adherent cells in patients with acute lymphoblastic leukemia during levamisol therapy. 12 children with acute lymphoblastic leukemia remaining in remission for 1-3 years, were studied during levamisol therapy. T-lymphocytes count, phagocytic activity of granulocytes the adherent cell number were investigated. The clinical state of patients before, during and after levamisol treatment was evaluated. The increased resistance to infections after levamisol therapy was noted. The rise of T-lymphocyte and phagocyting granulocytes number was observed in 70% of patients after 6 weeks of therapy. At the same time the decrease of phagocytic index was found. No essential variations in adherent cells count were noted. The patients who did not respond to the levamisol treatment relapsed in 2-3 months.


The study of T-, B-, O- lymphocytes in acute lymphoblastic leukemia. The T-, B-, and O-lymphocyte count changes were studied during the long-term intensive therapy of 43 ALL children. The control group consisted of 17 healthy children. The T-lymphocytes were identified by spontaneous formation of rosettes with sheep erythrocytes, the B-lymphocytes by EAC-rosette test. Patients were treated according to different program of multiple drug therapy and prophylactic cranial irradiation. During the study the applied therapeutic protocol produced the marked reduction of T- and B- lymphocytes. The decrease of B- lymphocytes was especially pronounced. The preliminary analysis suggests correlation between the reduction of T- and B- lymphocytes and prognosis.


Diagnostic specificity of autoantibodies. II. Clustering of autoantibodies--role in diagnosis and in comparison to E--and EAC-RFC peripheral blood profiles and immunoglobulin levels. Clustering of ANA and SMA was evaluated in patients with various internal diseases as a pattern of autoantibody formation. SMA was found in ANA positive patients with chronic hepatitis, undefined collagenoses and autoallergic thyroid diseases significantly more frequently, than in patients without any autoallergic disorders. The incidence of SMA in ANA positive cases with SLE and RA did not exceed their predictable by chance incidence. It was not found that clustering of autoantibodies is correlated with the E and C lymphocyte receptor abnormality as compared to the control group. The lowest count of E-RFC was found in SLE cases which differed significantly in this respect from the control group and also from chronic vasculitis cases. The clustering of autoantibodies is not correlated with hyperimmunoglobulinemia.


Studies on cell surface antigens of mouse leukemic and normal lymphocytes. III. Preparation and characteristics of alloantisera to differentiation antigens of mouse T lymphocytes. Preparation of antisera to alloantigens Thy-1, TL, Lyt-1 and Lyt-2 is described and the importance of adequate specificity controls indicated. The specificity and activity of antisera were characterized by trypan blue exclusion cytotoxicity assay, indirect membrane immunofluorescence and absorption using cell populations from different tissues of Thy-1, TL and Lyt congenic strains of mice. In the course of these studies new serologically detectable Lyt-1 linked alloantigen was discovered which shows wide tissue distribution.


[Unilateral deafness (author's transl)]. Unilateral conductive deafness has a readily determined aetiology in most cases. In contrast, unilateral sensorineural hearing loss requires more refined and extensive investigation. The most frequent causes of unilateral sensorineural hearing loss in our patients were sudden deafness, Menière's disease, cranio-vertebral dysplasia and cerebellopontine angle tumors. Early diagnosis of acoustic neuroma or other lesions of the internal auditory meatus or cerebellopontine angle requires special attention. The definitive diagnosis of these tumors often demands intensive clinical investigation but a high degree of suspicion may be entertained following modern routine audiometry, vestibular function testing and radiological examination. The importance of early diagnosis of these lesions is stressed with regard to the mortality rate for larger tumors and to the preservation of facial nerve function. The reliability of different diagnostic investigations is documented.


Ruptured choledochal cyst: recognition and management. A case is described of the rupture of a choledochal cyst in a 21-year-old man involved in a motor vehicle accident. At laparotomy, a haemoperitoneum was traced to a large haematoma in the lesser omentum which extended into the mesocolon and was found to be tinged with bile. Eventually it became apparent that the primary pathological condition was a large choledochal cyst into which opened the gallbladder. This cyst had split longitudinally down its anterior surface from the porta hepatis to the duodenum. Bile leakage was controlled by inserting a Foley catheter into the common hepatic duct, and inflating the balloon. Postoperative cholangiography showed massive cystic dilation of the intrahepatic ducts. Five days after the initial operation, a Roux-en Y cystjejunostomy was performed, and the patient has been well since. Crucial points in the emergency management of this condition appear to be in its recognition, and the provision of an adequate method of primary biliary drainage, if the condition of the patient demands staged management. End-to-end cystjejunostomy provides a satisfactory method of final drainage.


Duodenal "diverticulization" for massive haemorrhage from pancreatic pseudocyst. A case of massive haemorrhage into the gastrointestinal tract from a pancreatic pseudocyst is presented. The pseudocyst was a complication of acute pancreatitis, and control of the haemorrhage by operation was difficult because of the friability of the cyst wall. The surgical procedure called duodenal diverticulization is described and was found to be a useful adjunct to suture ligation for bleeding which was almost uncontrollable and when death of the patient seemed inevitable.


Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides. Purification and properties of the high-activity form of the enzyme. 1. The high-activity form of aminolaevulinate synthetase has been prepared from extracts of semi-anaerobically grown cells of Rhodopseudomonas spheroides, which were allowed to become activated in air. Specific activity was 130 000--170 000 nmol of aminolaevulinate/h per mg of protein at 37 degree C. 2. Enzyme fraction Ia prepared on DEAE-Sephadex was a mixture of four active enzymes, pI5.55, 5.45, 5.35 and 5.2, when prepared in either Tris or phosphate buffers and when extracts were activated by air or by cystine trisulphide. 3. The enzyme was further purified by preparative polyacrylamide-gel electrophoresis in imidazole/veronal buffer, pH 7.6, followed by gel filtration on Sephadex G-100 and concentration with DEAE-Sephadex. 4. The most active enzyme, pI 5.55, ran as a single protein band, mol.wt. 49 000, in sodium dodecyl sulphate and 2-mercaptoethanol. The apparent molecular weight under non-denaturing conditions was 62 000--68 000 on Sephadex G-100 or G-200, pH 7.5, and on polyacrylamide-gel electrophoresis, pH 8.5, at enzyme concentrations below 10 000 units/ml, i.e. less than 60 microgram of protein/ml, and the enzyme was mainly monomeric. 5. The enzyme was homogeneous by gel disc electrophoresis at pH 8.9 and 7.6, but a slightly more diffuse band of protein was obtained during electrophoresis in glycine buffer, pH 7.4. 6. Enzyme samples possessed an intrinsic yellow fluorescence when viewed under u.v. light and this fluorescence coincided exactly with enzymic activity on gel electrophoresis. Fluorescence maxima were 420 nm (excitation) and 495 nm (emission). 7. Radioactive 35S-labelled enzyme had 14 atoms of sulphur/mol of protein (or/40 leucine residues) of which 5--6 residues were cyst(e)ine and 8--9 residues were methionine. 8. Mo carbohydrate was detected apart from glucose, which prevented accurate determination of tryptophan with methanesulphonic acid and tryptamine.


Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides. Binding of pyridoxal phosphate to 5-aminolaevulinate synthetase. 1. Pyridoxal 5'-phosphate is a cofactor essential for the enzymic activity of aminolaevulinate synthetase from Rhodopseudomonas spheroides. It also aids activation of the low-activity enzyme by trisulphides such as cystine trisulphide, whereas inactivation of enzyme is facilitated by its absence. 2. The fluorescence spectrum of purified high-activity enzyme is that expected for a pyridoxal phosphate--Schiff base, but the firmly bound cofactor does not appear to be at the active centre. In dilute solutions of enzyme this grouping is inaccessible to nucleophiles such as glycine, hydroxylamine, borohydride and cyanide, at pH 7.4. 3. An active-centre Schiff base is formed between enzyne and added pyridoxal phosphate, which is accessible to nucleophiles. Concentrated solutions of this enzyme--Schiff base on treatment with glycine yield apo- and semi-apoenzyme, which can re-bind pyridoxal phosphate. 4. Two types of binding of pyridoxal phosphate are distinguishable in dilute solution of enzyme, but these become indistinguishable when concentrated solutions are treated with cofactor. A change occurs in the susceptibility towards borohydride of the fluorescence of the "structural" pyridoxal phosphate. 5. One or two molecules of cofactor are bound per subunit of mol. wt. 50 000 in semiapo- or holo-enzyme. The fluorescence of pyridoxamine phosphate covalently bound to enzyme also indicates one to two nmol of reducible Schiff base per 7000 units of activity in purified and partially purified samples of enzyme. 6. Cyanide does not convert high-activity into low-activity enzyme, but with the enzyme-pyridoxal phosphate complex it forms a yellow fluorescent derivative that is enzymically active.


The pharmacology of 1841 CERM, a new analgesic. A new non-narcotic analgesic, 2(3-trifluormethyl)-phenyl-tetrahydro-1,4-oxazine (1841 CERM) was compared with morphine, codeine and acetylsalicylic acid (ASA) in various pharmacological tests for analgesic activity. Studies for possible tolerance and physical dependence liability were also carried out. In these tests, 1841 CERM was a more powerful analgesic than morphine, and particularly codeine when given orally. It did not lead to tolerance or physical dependence.


Hyperalgesia after treatment of mice with prostaglandins and arachidonic acid and its antagonism by anti-inflammatory-analgesic compounds. Prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) and arachidonic acid have been demonstrated to potentiate the peritoneal writhing response in the mouse induced by benzoquinone. The resultant dose-response relationships were bell shaped with a maximum activity of 10 ng/kg i.p. of potentiating agent. Floctafenine, indometacin and acetylsalicylic acid (ASA) blocked the potentiation induced by arachidonic acid but not that induced by PGE2. This suggests that it is prostaglandin that causes the potentiation and that the mechanism of action of ASA-like drugs against hyperalgesia associated with inflammation is blockade of prostaglandin synthesis. Morphine reduced the potentiation by PGE2 and arachidonic acid but the bell shaped hyperalgesia was still evident using both agonists. These results indicate that morphine does not inhibit prostaglandin synthetase but may modify the effect of prostaglandin. This method may be useful to distinguish between ASA-like and morphine-like analgesic compounds using a pain response in vivo.


Correlations of DNA, RNA and protein levels in duodenal mucosa with antiinflammatory potency and disposition to gut damage of non-steroidal agents. Comparative behaviour of glucametacine, indometacin, phenylbutazone and ibuprofen. As far as molar ratio is concerned, glucametacine was half as potent as indometacin, twice as active as phenylbutazone and four times more effective than ibuprofen in preventing cotton granuloma. Both indometacin and phenylbutazone induced dose related gastrointestinal ulcerations and increase of 51Cr tagged erythrocytes in feces. The former drug displayed gut toxicity at anti-inflammatory doses, the latter at doses approximately four times larger. Glucametacine was still devoid of damaging effects at a dose ten times larger than the minimal one capable of inhibiting granuloma growth. Ibuprofen, too, failed to induce ulcers at all doses examined; however, it displayed a trend toward gut bleeding when doses that increased blood corticosterone were attained. Studies on duodenal mucosa showed that in rats on cotton granuloma, DNA, proteins and DNA:RNA ratio increase as compared to unimplanted rats. Glucametacine and phenylbutazone reversed the increase of DNA and proteins, respectively. Indometacin decreased all forementioned constituents of duodenal mucosa while inducing haemorrhages and ulcers on gut. Furthermore, in naive rats, unlike glucametacine and phenylbutazone, indometacin induced a decrease in protein content of duodenal mucosa. Differences in disposition of gut toxicity among glucametacine and other anti-inflammatory drugs are discussed.


Trimethoprim and sulphamethoxazole inhibition of haematopoiesis in vitro. The effect of trimethoprim and sulphamethoxazole on haematopoiesis was studied in vitro using cloning techniques for human and murine erythroid and granulocytic precursor cells. Trimethoprim was found to inhibit granulopoiesis and erythropoiesis in vitro in a dose-dependent fashion with approximately 50% inhibition of human erythroid and granulocytic colonies at a therapeutically achievable concentration of 7 micrograms/ml. Sulphamethoxazole was also shown to impair haematopoiesis in vitro. The inhibition caused by both these constituents of co-trimoxazole was completely reversed by folinic acid. The data suggest that co-trimoxazole can impair human haematopoiesis by inhibition of tetrahydrofolate synthesis. These observations suggest that the clinical haematopoietic toxicity of trimethoprim-sulphamethoxazole can be abrogated by simultaneous administration of folinic acid.


Stimulation of human haemopoietic cells by colony stimulating factors: sensitivity of leukaemia cells. The sensitivity of populations of human granulocyte precursors to factors with colony stimulating activity (CSA) was assessed in agar culture in vitro. The mean threshold of stimulation was estimated by analysis of dose-response curves of clone growth against concentration of CSA. This method of assessment has the advantage that CSA production by cells contaminating the population under test does not affect results. Marrow cells from patients with acute myeloid leukaemia were less sensitive to CSA than marrow cells from normal individuals. Sensitivities of cells from chronic granulocytic leukaemia and from chronic myelomonocytic leukaemia were within the normal range, but this group also tended to require more CSA than controls. In addition, sensitivities of granulocyte precursors from patients with acute myeloid leukemia were closely related to the culture pattern, and thus to the remission probability. The significance of this relationship is discussed.


An animal model of Fusarium solani endophthalmitis. Infection with Fusarium solani was established by injecting spores into the anterior chambers of outbred Wistar rats. The disease produced was remarkably similar to that reported in man and progressed to a fulminating endophthalmitis. Attenuation of the disease could be accomplished by repeated animal passage of the isolate.


Histiocytosis X: current concepts and a report of two cases. The current concepts of histiocytosis X are discussed, and the literature concering this rare disease of obscure aetiology reviewed. Two case reports of histiocytosis X presenting in similar sites in young children of similar ages, but with markedly different courses, are presented. The importance of early recognition of the disease, particularly by the dental surgeon who may see the first oral signs, is stressed. Attention is drawn to the danger of misdiagnosing the oral signs of histiocytosis X, particularly as periodontal disease. The possible aetiologies are examined and current treatment regimes discussed.


Metabolism of polyadenylated mRNA in growing human lymphocytes. The kinetics of degradation of newly synthesized, cytoplasmic polyadenylated RNA have been examined in normal human lymphocytes stimulated to grow with phytohemagglutinin. A single class of poly(A)-bearing RNA was identified with a half-life of approximately 50 h. In the presence of actinomycin D, the half-life was 5 to 6 h, and virtually no decay of pulse-labeled material was detectable after 6 h of chase incubation with cordycepin. These findings contrast sharply with data obtained from other growing human cells used as controls: polyadenylated mRNA in MOLT-4 cells, a cultured line of T lymphocytes, had a half-life of 2 h in the presence of actinomycin D. The stability of poly(A)-containing RNA in stimulated lymphocytes from normal donors is therefore not simply a manifestation of cell proliferation. In normal resting lymphocytes, Berger and Copper [(1975) Proc. Natl. Acad. Sci. U.S. 72, 3873--3877] reported the existence of 2 classes of polyadenylated mRNA with half-lives of under an hour and greater than 20 h, respectively. Since short-lived poly(A)-bearing mRNA is absent from mitogen-stimulated lymphocytes, the data suggest that stabilization of previously labile poly(A)-bearing RNA is one of many carefully regulated processes accompanying growth induction in normal lymphoid cells.


Reaction of blood with artificial surfaces of hemodialyzers. Studies of human blood with platelet defects or coagulation factor deficiencies. Heparinized human blood was exposed to the dialysis membranes of commercially available pediatric size hemodialyzers in an in vitro flow circuit. Bloods from normal subjects and from patients with various blood coagulation and platelet function deficiencies were tested in this model system. In most cases, there was a heavy linear deposit of leukocytes on the dialysis membrane overlying support structures. In other areas, the cellular deposit was less uniform and consisted of single platelets, platelet aggregates, leukocytes, and occasional fibrocellular microthrombi. The number of adherent platelets was smaller in tests with blood from patients with congenital afibrinogenemia, factor XII deficiency, severe von Willebrand's disease, and thrombasthenia then in tests with blood from normal subjects or hemophilic patients. Hence, fibrinogen, factor XII, the von Willebrand factor, and a normal platelet plasma membrane appear necessary for adhesion of platelets to dialysis membranes.


Influence of thymosin on E-rosette formation of lymphoid cells in leukemic and nonleukemic children. The influence of two thymosin and two spleen control preparations on the E-rosette formation of peripheral blood lymphocytes and leukemic cells from non-leukemic children with depressed T cell values and leukemic children was investigated. Both thymosin preparations but also one of the control preparations induced a significant increase in the mean percentage of E-rosette forming PBL in the non-leukemic children with depressed T cell values. Thymosin and spleen preparations, however, did not convert the non-erythrocyte binding blasts to erythrocyte binding cells in either common or pre-T-ALL.


Pharmacology of 5-hydroxytryptamine receptors in frog skin epithelium. 1. 5-Hydroxytryptamine (5-HT) stimulates active sodium transport and decreases the passive mucosal to serosal chloride permeability across frog skin. The relative importance of the different regions of the 5-HT molecule in the mediation of these responses has been studied using a range of structurally related compounds. 2. Substitution in the ethyl amine side chain of 5-HT (5-hydroxytryptophan) results in decreased receptor affinity and intrinsic activity; removal of the side chain (5-hydroxyindole) abolishes activity. Methoxy substitution of the 5-OH moiety of 5-HT has no effect on intrinsic activity but reduces affinity; displacement of the hydroxyl group to position 6 diminishes intrinsic activity and affinity. 3. It is concluded that both of the 5-HT-induced physiological effects are mediated via a single receptor which is distinct from alpha- and beta-adrenoceptors.


Clinical and angiographic determinants of early mortality related to aortocoronary bypass surgery. Clinical and angiographic features were identified that influences early mortality in 807 patients who underwent aortocoronary bypass grafting alone among the first 1000 consecutive patients subjected to aortocoronary bypass operations at the Montreal Heart Institute. The early mortality was 4.7% and was related to the patient's age, the duration of the illness from its first clinical manifestation, certain types of clinical presentation, electrocardiographic findings, the number of obstructed arteries and the ejection fraction. The influence of the number of obstructed arteries appeared to be independent of other factors, including the number of grafts and the degree of correction. Early mortality was not influenced by risk factors such as lipid abnormalities, hypertension or diabetes, by the history of previous myocardial infarction or the number of grafts.


Spontaneous aortoduodenal fistula: successful treatment by extra-anatomic vascular bypass. A 77-year-old woman was admitted to hospital with massive upper gastrointestinal bleeding of obscure etiology and a palpable abdominal aortic aneurysm. A spontaneous aortoduodenal fistula, discovered at operation, was treated successfully by resection of the aneurysm, aortic closure, lateral duodenal repair and axillobilateral femoral grafting. The three clues to the correct diagnosis were: a palpable, pulsatile abdominal mass, recurrent abrupt cardiovascular collapse and significant upper gastrointestinal bleeding with no obvious source. The conventional method of treatment--aortic resection, duodenal repair, and intra-abdominal aortic grafting--is followed by secondary infection and aortic anastomotic bleeding, and by death in nearly 50% of the patients. The method of treatment used by the authors in this patient may be safer and deserves further consideration.


Ischemic colitis associated with hypertension. A 48-year-old man with accelerated hypertension developed right-sided ischemic colitis. There was no evidence of another cause of vascular inadequacy. Microscopically, the bowel showed ischemic alterations of different stages. The arterial alterations of different stages. The arterial vessels showed minimal changes. In older lesions, fibrosis was prominent and the mucosa was atrophic. In more recent lesions, some vessels of the submucosa were plugged with fibrin and the overlying mucosa was infiltrated by nonorganized hemorrhage and cellular elements.


Intraoperative blood-flow responses in coronary artery bypass grafts. Intraoperative graft flow responses in 15 patients who underwent coronary artery bypass grafting (CABG) were studied systematically. The mean blood flow for 13 left anterior descending (LAD) coronary artery grafts was 64 +/- 20 ml/min and for 12 right coronary artery (RCA) grafts was 53 +/- 13 ml/min. Of these, systolic flow was dominant in one LAD and three RCA grafts, suggesting the perfusion of the right ventricle or the noncontractile left ventricle segment, or both. Five LAD and two RCA grafts had a negligible reactive hyperemic response, and the underlying cause for this can be futher examined by observing their phasic flow patterns. Temporary occlusion of the coronary artery proximal to the site of anastomosis produced increased flow in 8 grafts, indicating the presence of competitive flow; decreased flow was observed in 15 grafts, indicating the presence of proximal retrograde flow which may play a role in the proximal occlusion of the bypassed artery later. Thus intraoperative flow studies supplement the preoperative angiographic findings in elucidating the pathophysiology involved and are useful in evaluating CABG operations.


[Posterior rectotomy indications for villous tumors]. The posterior (Kraske) approach to the surgical management of villous tumours of the rectum was used in 12 patients. One patient died in the postoperative period and in six others there were complications (wound infection in three, wound infection and rectal hemorrhage in one, wound dehiscence in one and cellulitis in one), but there was not a single fistula. This approach represents an easy and well-tolerated operation especially in older patients who are otherwise poor operative risks. The posterior approach is also excellent for excising lesions of the mid-rectum that may be too bulky for endoscopic removal and too proximal for their excision through the dilated anus. The procedure is not appropriate for malignant tumours and the benign nature of these tumours is best appreciated preoperatively by digital palpation; however, confirmation of their exact nature requires microscopic examination of the whole lesion.


Selective superior mesenteric embolization for small intestinal hemorrhage. A 25-year-old white woman who had previously undergone two operations for peptic ulcer disease, and was addicted to drugs and alcohol, had massive hemorrhage from the small intestine. Angiography pinpointed the jejunum as the source of bleeding. Because the patient had a coagulopathy she was considered a poor risk for surgery. Bleeding was controlled by embolization with sterile, commercially available Gelfoam (Upjohn) which was injected into the offending branch of the superior mesenteric artery. This is believed to be only the third documented case of embolization of small intestinal vessels. A review of the available literature is presented and the value of Gelfoam embolization as an adjunct in the control of hemorrhage in selected patients is stressed.


Action of inhibitor released from neutrophils and leukemic blast cells. The concept that polymorphonuclear leukocytes, or neutrophils, play a role in feedback control of granulopoiesis has been supported by the finding in bone marrow culture studies that mature neutrophils inhibited formation of granulocytic colonies. The study described in this paper was done to investigate the mechanisms involved. With the use of a modified assay it was found that mature neutrophils released factors that reduced the proliferation of colony-forming cells in cultures stimulated by cell-free colony-stimulating factor. In myeloproliferative and myelodysplastic disorders the amount of inhibitor released by the neutrophils varied greatly. Leukemic blast cells also released inhibitor, and in some cases the amount released per cell was greater than the amount released from normal mature neutrophils. The inhibitory factors released from the neutrophils differed from those previously described in the literature in terms of mode of action and apparent molecular size.


Evidence that xylosyladenine affects methylation by inhibition of S-adenosyl-L-methionine synthesis. The adenosine analogs, 9-beta-D-xylofuranosyladenine (XA) and 3'-deoxyadenosine (cordycepin) were tested for their ability to interfer with S-adenosyl-L-methionine (SAM) formation in L1210 cells in vitro. XA inhibited the incorporation of [3H]methionine into SAM in a mixed-competitive manner, while cordycepin was not inhibitory. The adenosine deaminase inhibitor, 2-deoxy-coformycin produced a marked potentiation of the inhibitory effect of XA on Sam synthesis, but did not affect the inactivity of cordycepin. These results indicate that the inhibitory action of XA, but not cordycepin, on the methylation of nuclear RNA may be attributed to interference with the synthesis of SAM.


Emergency transhepatic obliteration of bleeding varices. Transhepatic obliteration of gastroesophageal varices was performed in 18 actively bleeding patients. The success of the procedure was related to the complete obliteration of the varices, as demonstrated by their disappearance at angiography. In 13 of the 14 patients in whom obliteration was complete, bleeding did not recur. Three of the 13 died of hepatic insufficiency within 18 days of embolization, and three refused surgery and were lost to follow-up. The remaining seven patients had portacaval or mesocaval shunts, and are doing well at a follow-up of 12 months. Transhepatic obliteration has, therefore, proved to be an effective emergency procedure in patients who will be acceptable surgical candidates at a later date.


Maturation of the hypothalamo-neurohypophysial system. II. Neurophysin, vasopressin and oxytocin in the median eminence of the developing rat brain. Transverse sections of the median eminence from fetal and neonatal rats were examined by the immunoperoxidase technique to detect the presence of oxytocin, vasopressin and neurophysin. Neurophysin was observed in the 18-day fetus. Vasopressin and oxytocin were not detected until after birth, on the 4th and 8th days respectively. There was an accumulation of material crossreactive with neurophysin and vasopressin antibodies in the palisade layer of the median eminence between the 4th and 9th days after birth. This distribution of immunoreactive material in the palisade layer was suggestive of neurosecretory substances localized in two fibre tracts on either side of the median eminence. The data are consistent with the accumulation of corticotropin releasing factor and an associated neurophysin in this area. It is suggested that the accumulation of material occurs because of the relative immaturity of the capillary loops that constitute the primary plexus of the hypophysial portal system.


Reconsideration of influenza A virus nomenclature: a WHO memorandum. The system of nomenclature for influenza A viruses recommended by WHO in 1971 provided a basis for the designation of these viruses into types based on their nucleoprotein antigens. Influenza A viruses were further divided into subtypes based on the antigenic character of their haemagglutinin and neuraminidase components. To review the relevance to influenza virus nomenclature of new information on the antigenic and molecular characterization of influenza A viruses a meeting was held in Atlanta, GA, USA, in November 1978 under the auspices of WHO. Although the 1971 system of nomenclature has worked well, new information on relationships between haemagglutinin and neuraminidase subtypes indicates that the number of subtypes could be reduced. However, for the present, the participants in the meeting recommend that the 1971 system should still be used, without modification, at least until a further meeting is held in 1980. In the meantime, WHO wishes to encourage studies that will further define these relationships and solicits comments relevant to the proposals outlined in this Memorandum.


Assessment of insecticidal impact on the malaria mosquito's vectorial capacity, from data on the man-biting rate and age-composition. The reduction in average age of a vector population after application of a residual insecticide is commonly interpreted under the implicit assumption that the vector population is uniformly exposed to the insecticide. This assumption maximizes the calculated impact of the insecticide on the vectorial capacity. An alternative assumption, namely that the vector population is composed of two subpopulations, one endophilic and exposed, the other exophilic and not exposed, leads to a much smaller calculated impact of insecticide on the vectorial capacity. This is illustrated with data collected before and after application of propoxur in the Garki District, Kano State, Nigeria. These data were also used to estimate, on the one hand, before spraying, the proportion of blood meals taken by Anopheles gambiae s.l. on man that are followed by rest indoors, and on the other hand, after spraying, the proportion exposed after the first blood meal, according to the model of non-uniform exposure; the two estimates agree fairly well. The discussion compares the models of uniform and non-uniform exposure in terms of plausibility and concludes that the latter is more realistic. It is therefore prudent to take it into account when evaluating the impact of insecticides on the transmission of malaria.


A comparison of cardiovascular measurements in the Gambia, Jamaica, and the United Republic of Tanzania. Epidemiological studies of the cardiovascular characteristics of three typically rural communities in the Gambia, Jamaica, and the United Republic of Tanzania were carried out by means of standardized methodology. This paper reports comparisons of arterial blood pressure distribution and electrocardiographic findings in relation to age, sex, and body build. Marked differences in blood pressure were found, with higher values in Jamaicans than in Tanzanians, who in turn had higher values than Gambians. These differences are not explicable in terms of body build. Heart rates and ECG amplitudes were also strikingly different, with higher values in Jamaicans than in Tanzanians and Gambians. The differences in ECG amplitudes cannot be explained by differences in body build, heart rate, or blood pressure. The findings agree with the hypothesis that some factor or factors associated with development contributes to the risk of cardiovascular disease in peoples of African origin.


Myocardial infarction and water hardness in the WHO myocardial infarction registry network. The negative association between water hardness and cardiovascular disease found by several authors in different countries has also been found in the present investigation. All cases of myocardial infarction were registered in a standardized way at 15 WHO Collaborating Centres in Europe; information on the hardness of drinking water used by the population studied was also collected. Higher rates of myocardial infarction were usually found in towns served by softer water.


Comparison of methods for estimating the frequency of paralytic poliomyelitis in developing countries. Standard reporting systems have proved to be unreliable in estimating the frequency of paralytic poliomyelitis in many developing countries. The effectiveness of three survey methods for estimating the prevalence of lameness attributable to poliomyelitis were compared in the Danfa Health Project district of rural Ghana. Lameness was studied because it is easily identified by inexpensive survey techniques. A postal survey of school headteachers was the least costly and most accurate method, giving a prevalence of lameness attributable to poliomyelitis of 7.2 per 1000 schoolchildren. This method is recommended for countries with an extensive network of primary schools. Medical examinations in a village health survey yielded a prevalence of 4.6 per 1000 children aged 6-15 years. This method was relatively expensive but could be justified if the survey was multipurpose. A question added to the annual district census showed a prevalence of 2.2 per 1000 children, a rate still many times higher than estimates from national statistics. The inclusion of such a question in a census or other national survey entails little additional cost and with more careful questioning results should improve. Repeated surveys can be used to assess the success of poliomyelitis vaccination programmes.


Measuring the efficacy of vaccination in affording protection against plague. The relationship of F1 antibody titre to protection against plague was investigated by subjecting seropositive laboratory rats to virulent challenge and observing for survival. The passive haemagglutination (PHA) test in microtitre was employed for serology. Rats vaccinated with live vaccine EV76 (51f), killed U.S.P. vaccine, or F1 antigen and challenged by subcutaneous inoculation of 1 x 10(3) to 5 x 10(5)Yersinia pestis survived at similar rates that, overall, equalled 6% at titres less than 1:16, 46% at titres of 1:32-1:64, 90% at titres of 1:128-1:256, and 96% at titres of 1:512-1:1024. Rats vaccinated with F1 antigen and rats that had been infected previously were challenged intranasally with 8.9 x 10(4)Y. pestis and subsequently demonstrated similar rates of survival that was zero at titres less than 1:128, 86% at titres of 1:128-1:256, and 100% at titres of 1:512-1:1024. The significance of titre of F1 antibody as a measure of seroimmunity against acute bubonic or pneumonic plague is discussed for rats, monkeys, and man.


The effect of diethylcarbamazine in a murine model of Brugia malayi microfilaraemia. The effect of diethylcarbamazine was tested in a murine model of Brugia malayi microfilaraemia. A course of therapy similar to that used to treat human infection led to more than a 90% decrease in circulating parasites. Experiments in which different amounts of diethylcarbamazine were given as a single dose indicated that its microfilaricidal activity is dose-dependent. The animal model of B. malayi microfilaraemia may be useful for studies of the mechanism of action and pharmacology of diethylcarbamazine and may be applied to the screening of new microfilaricidal drugs.


Assessment of host defence against infection during chemotherapy of Hodgkin's disease. Simultaneous measurements of leucocyte numbers and function have been made during combination chemotherapy for advanced Hodgkin's disease. There was a marked fall in the numbers of circulating mononuclear cells during the chemotherapy cycle in many patients. The migratory, phagocytic, candidacidal, and bactericidal activities of polymorphs and monocytes were frequently depressed. Patients often showed isolated abnormalities while clinically free from infection. In contrast, simultaneous depression of several parameters appeared to be associated with infection.


'Double marker' lymphocytes in patients receiving tetracycline. When T and B cell counts, using sheep cell rosettes and surface immunoglobulin as markers, are done on the lymphocytes of individuals who are receiving tetracycline, unusually high numbers of 'double marker' cells are regularly found.


Cloning of T-lymphocytes in systemic lupus erythematosus. Colony-forming T-lymphocytes were studied in the blood of twenty-two patients with systemic lupus erythematosus (SLE) by the technique of plating phytohaemagglutinin (PHA) stimulated lymphocytes in soft agar. The mean count of T-lymphocyte colonies in SLE of 70+/-64 (1 s.d.)/mm3 of blood was considerably less than the count of 218+/-102/mm3 for healthy young adults and of 139+/-99/mm3 for aged persons. In SLE, counts of T-lymphocyte colonies correlated with low counts of T-lymphocytes in blood and with other indices of T-lymphocyte impairment. The data point to derangement of factors which influence the capacity of T-lymphocytes to proliferate, but it cannot be stated to what degree this is a cause and/or result of the autoimmune disease process associated with SLE. Cloning of peripheral blood T-cells could help determine whether the essential defect in SLE is in the T-lymphocyte or one of its sub-sets, or in factors produced by adherent cells which are essential for growth in vitro of T-lymphocyte colonies.


Effects of Corynebacterium parvum and BCG therapy on immune parameters in patients with disseminated melanoma. A sequential study over 28 days. II. Changes in non-specific (NK, K and T cell) lymphocytoxicity and delayed hypersensitivity skin reactions. C. parvum and BCG produced significant changes in NK, K and T cell lymphocytotoxicity using a Chang liver target cell. A consistent temporal pattern over 28 days of early depression, recovery, overshoot and then decline was described. This was particularly marked for C. parvum and 'K' cell activity. Skin test reactivity to recall antigens at 28 days was not appreciably different from the pre-immunization reactivity. The importance of using lymphocyte concentration-cytotoxicity titration curves and the linearization of such curves is discussed. An immunotherapy schedule with 3 weekly immunization intervals is proposed as the optimum schedule in patients receiving C. parvum at a dose of 2.0 mg/m2 i.v.


Immunological dysfunctions in multiple sclerosis. I. Diminution of 'active' thymus-derived lymphocytes and presence of immunomodulating serum factors. The peripheral blood of twenty-eight patients with multiple sclerosis (MS) was examined for 'active' thymus (TA) derived lymphocytes (PBL) and the presence of serum factors which impair the lymphocyte blastogenic response and the migration of leucocytes from capillary tubes. MS patients exhibited a significant reduction in the level of circulating TA lymphocytes (15.2+/-2.7 vs 22.9+/-2.9, P less than 0.001). Additionally, MS serum markedly impaired the mobility and the mitogen induced blastogenic response of autologous and allogenic (control) PBL. Impairment in the blastogenic response was observed only when serum was added at culture initiation or after 4 hr. The results support the concept of a generalized deficiency in the immune competence of MS patients. The pathophysiological role of a serum suppressive factor is discussed.


Human monocyte-lymphocyte interaction and its enhancement by levamisole. We investigated the role of monocyte-lymphocyte interaction in the transformation of human peripheral blood lymphocytes by the mitogen concanavalin A (Con A). Human monocytes were separated from lymphocytes and were transiently exposed to Con A. The Con A-pretreated monocytes were able to subsequently bind autologus lymphocytes by a process that was selective for T cells. This interaction required the initial presence of Con A at the monocyte surface, and became independent of surface bound ligand after 72 hr. Levamisole, an agent thought to facilitate the participation of monocytes in the cellular immune response, enhanced the binding of lymphocytes to monocytes at low concentration of Con A (5--10 micrograms/ml). Levamisole did not lead to mitogen independent lymphocyte binding. The association between lymphocytes and Con A-pretreated monocytes resulted in the mitogenic transformation of lymphocytes in the absence of soluble Con A in the medium. These results suggest that, in addition to any possible soluble mediators, direct lymphocyte-monocyte contact is required for optimal mitogenic transformation. This T-cell-monocyte interaction over time becomes independent of cell-surface mitogen. The ability of levamisole to enhance this interaction may explain levamisole's capacity to stimulate lymphocyte proliferation.


Evidence for antibody-dependent cell-mediated cytotoxicity by T cells bearing receptors for IgG. Human lymphocyte populations comprising T cells, T depleted lymphocytes, and T cells enriched for, or depleted of, IgG Fc receptor-bearing (TG) cells, were separated using rosette techniques. All lymphocytes were assessed for the ability to lyse antibody-coated chicken erythrocytes and SL2 mouse lymphoma cells. Their activity was compared with that of monocytes and neutrophil-enriched preparations. IgG Fc receptor positive cells within the T population were highly active in both cytotoxicity assays; the activity could not be ascribed to contamination by monocytes or neutrophils. The TG cells forming junctions with the target cells possessed a characteristic ultrastructure.