Cutaneous melanoma and its relation to melanoma of the uveal tract.

Current tactics under study in the control of cutaneous melanoma may prove to be of benefit in management of uveal melanoma. These include precise staging at diagnosis and analysis of pathologic data correlated with the subsequent clinical course. The potential role of adjuvant chemotherapy and immunotherapy is discussed.


A rapid chromatographic method for quantitation of high molecular weight fibrinogen derivatives in plasma.

High molecular weight fibrinogen derivatives were precipitated from 3 ml of plasma by 0.88 M ammonium sulphate. The resuspended precipitate was analyzed by chromatography on a 2.5 x 30 cm glass bead Bio-Gel 5 M column by using a flow rate of 60 cm/hr and continuous effluent monitoring at O. D. 280 nm. Complete elution of fibrinogen occurred in 50 min. Elution profile was handled according to the chromatographic plate theory analysis. Results obtained by our method were not significantly different from those obtained by conventional chromatography.


Tissue thromboplastin activity of isolated human monocytes.

Certain agents that induce spreading of or increased content or release of lysosomal enzymes from human monocytes also induce a dramatic increase in tissue thromboplastin content of the cells. The increase is inhibited by cycloheximide and actinomycin D and does not appear in granulocyte, lymphocyte or platelet populations treated in the same way. The effect of several other substances on the development of monocyte tissue thromboplastin activity is reported.


The influence of residual factor VII on the sensitivity of brain thromboplastin.

One-stage prothrombin times of normal and of factor VII-deficient beagle plasma were determined with two types of beagle brain thromboplastin, one prepared from normal beagles and the other from factor VII-deficient beagles. There was little difference between the reagents in the prothrombin times obtained for normal plasma. However, when factor VII-deficient plasma was tested, reagent prepared from factor VII-deficient beagles gave considerably longer prothrombin times than were obtained with the normal reagent and the difference increased with increasing reagent concentration to a maximum at 140 mg/ml. Prothrombin times of a series of mixtures of normal and factor VII-deficient plasma indicated that the presence of only 1/90 part of normal plasma was necessary to compensate for the difference between the two reagents. Determination of the iron content of the reagent suggested that the microcirculation of an average brain contained some 1.8 g of whole blood. The finding that brain thromboplastin prepared from factor VII-deficient beagles is more sensitive to a deficiency of factor VII in plasma, presumably a result of the smaller quantity of factor VII present in the reagent, is compatible with the known kinetics of extrinsic coagulation.


The influence of thrombin on the clotting activity of factor VIII. A study with insolubilized thrombin.

An investigation of the influence of thrombin on the clotting activity of factor VIII was made. Purified factor VIII and different amounts of thrombin complexed to Sepharose 4 B were mixed and incubated for various periods of time. The factor VIII activities of these incubation mixtures were determined by the one- and two-stage analytical procedures in the presence of the thrombin-sepharose and in its absence following the latter removal from the test sample by filtration. The results so obtained confirm the view that thrombin inactivates factor VIII. Evidences for a thrombin-induced potentiation of the factor VIII activity, seen only in the thrombin-sepharose containing test samples analyzed by the one-stage method, are here interpreted as thrombin-effects peculiar to this factor VIII test system and not as potentiation by thrombin of the factor itself.


The determination of antithrombin III. Comparison of six methods. Effect of oral contraceptive therapy.

At III levels measured with six methods in 36 people: 10 healthy controls, 10 women taking a progestagen Lynestrenol and 16 women taking a combined oestrogen-progestagen contraceptive pill. The reproducibility and the sensitivity of these methods as well as the correlation between methods were studied. The Hensen and Loeliger technique had a poor reproducibility and the results obtained with the Howie technique were not in good correlation with those obtained with other methods, especially in the group taking oral contraceptives. The two amidolytic methods using chromogenic substrates were found to be very accurate for antithrombin III activity determination. The rocket immunoelectrophoresis was more accurate and more practical than the radial immunodiffusion. With all methods--except the one of Howie--the 10 women taking progestagen Lynestrenol and the 16 taking combined oestrogen-progestagen had a low AT III and differed significantly from the 10 normals tested. No difference was observed between women taking progestagen only or an oestrogen-progestagen combination.


Inhibition of urokinase by complex formation with human antithrombin III in absence and presence of heparin.

Human antithrombin III was purified from fresh human plasma by affinity chromatography on heparin-Sepharose, affinity chromatography on concanavalin A Sepharose, gel filtration on Ultrogel AcA 34, ion exchange chromatography on DEAE A-50 Sephadex and preparative agarose gel electrophoresis. The hydrolytic activity of urokinase (plasminogen activator from urine) on acetyl-glycyl-L-lysine methylester acetate (Ac-gly-lys-OMeAc) was inhibited by antithrombin III in a slow time-dependent manner. Heparin accelerated the reaction between activator and inhibitor. Inhibition of catalytic activity was associated with the formation of an 1:1 molar complex between activator and inhibitor as revealed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The complex was also demonstrated by crossed immunoelectrophoresis against anti-antithrombin III.


Immunologic studies of antithrombin III heparin cofactor in the newborn.

Serial quantitative immunoelectrophoretic (IE) measurements of antithrombin III heparin cofactor (AT III) were made in groups of well and sick newborn infants classified by gestational age. Collection methods (venous vs. capillary) did not influence the results; serum IE measurements were comparable to AT III activity by a clotting method. AT III is gestational age-dependent, increasing from 28.7% of normal adult values at 28--32 weeks to 50.9% at 37--40 weeks, and shows a gradual increase to term infant levels (57.4%) by 3--4 weeks of age. Infants with the respiratory distress syndrome (RDS) show lower levels of AT III in the 33--36 week group, 22% vs. 44% and in the 37--40 week group, 33.6% vs. 50.9%, then prematures without RDS. Infants of 28--32 week gestational age had only slight differences, RDS = 24%, non-RDS = 28.7%. The lowest levels of AT III were seen in patients with RDS complicated by disseminated intravascular coagulation and those with necrotizing enterocolitis. Crossed IE on representative infants displayed a consistent pattern which was identical to adult controls except for appropriate decreases in the amplitude of the peaks. The thrombotic complications seen in the sick preterm infant may be related to the low levels of AT III.


Thrombin generation and neutralization test (TGNT) - a simple, practical, and sensitive assay for plasma heparin quantitation.

A simple, quantitative method for detection of small amounts of heparin in human plasma is described. This method is based on the activation of coagulation factor X to its enzymatic form (Xa), by a mixture of RVV platelet substitute (Esnouf and Williams 1962, Esnouf and Jobin 1967) in a plasma rendered fibrinogen free without affecting other clotting factores (Bell et al. 1968, Bell 1973), by Arvin (Ancrod). Activation of factor X, results in thrombin generation. Thrombin inactivation by its natural inhibitors depends on the time elapsed from the start-point of activation. The inactivation process is enhanced by heparin (Biggs et al. 1970, Blombäck et al. 1963) and this enhancement depends on the quantity of heparin in the plasma.


Comparison of reagents for determining the activated partial thromboplastin time.

Six commercially available reagents for the determination of the activated partial thromboplastin time have been evaluated and compared with respect to their sensitivity to the coagulation factors VIII, IX and XI and to their response to heparin. Some variation was observed among the reagents regarding their sensitivity to factor XI and even greater differences were obtained with factors VIII and IX. It was also clear that none of the reagents was sensitive to the same extent to the factors tested. The sensitivity to heparin shows considerable variation, in terms of time as well as mode of response to increasing heparin levels. In four reagents this response is linear, it is logarithmic in one and the remaining one is yet again different. It seems unlikely that any standardization of the APTT determination is at present possible with the reagents studied.


Quantitative estimation of coagulation factors in liver disease. The diagnostic and prognostic value of factor XIII, factor V and plasminogen.

20 coagulation parameters were investigated in 144 patients with different liver diseases. The groups of acute hepatitis, chronic active hepatitis and liver cirrhosis were compared and the prognostic value of the coagulation analyses investigated. It is clear that the determination of the factor V activity is a good and easy test for detection of actual liver function. Repeated controls over several weeks revealed with a statistical significance (p less than 0.0005) that all patients with a factor XIII below 35% and a plasminogen below 19% will die in liver coma, if they have not died beforehand from acute gastrointestinal haemorrhage, acute infection or cardiac arrest. Plasminogen is also lower in the group of non-survivors but the values of the two groups are overlapping and of no prognostic help in a single case. The possible causes of the diminution of factor XIII activity are discussed.


Acquired inhibitors of factor V.

The clinical and laboratory data on the 12 patients with an acquired inhibitor to factor V have been reviewed. The degree of clinical bleeding in these patients varied from none to severe, and in most patients the inhibitor was transient. The combination of a markedly prolonged partial thromboplastin time and Quick prothrombin time and failure of normal plasma to correct these tests, in the presence of a normal thrombin and prothrombin and proconvertin time, seems to be pathognomonic for a factor V inhibitor. The inhibitors have physicochemical properties of immunoglobulins and a few have been characterized as polyclonal IgG antibodies or a mixture of IgM and IgG antibodies. The etiology and pathophysiologic mechanism of their development is unknown, but there seems to be a close relationship to major surgery. When tested with inhibitor plasma, the plasmas from 9 patients with hereditary factor V deficiency from 7 unrelated families did not contain factor V antibody-neutralizing material.


Treatment of congenital factor VII deficiency with a new concentrate.

A new factor VII concentrate, made from ACD plasma by a process involving successive absorptions of cryoprecipitate supernatant on DEAE Sephadex and of the resulting supernatant on A1(OH)3, was administered to 10 patients with severe factor VII deficiency. 5 patients received only one dose for treatment of a single bleeding episode, the remaining 5 were given multiple infusions (47) for spontaneous hemorrhages or for the prevention of surgical bleeding. In vivo factor VII recovery ranged from 43 to 126% (average 88%) of the assayed in vitro activity of the concentrate. A dose of 0.5 u/kg was found to produce a 1% rise of the plasma factor VII levels. The mean half-life on injected factor VII as assessed in 7 kinetic studies was 205 min (range 168--234). Spontaneous bleeding was easily controlled by the concentrate and major surgical procedures (two tonsillectomies) could be performed without complications. 1 patient developed HBSAg positive hepatitis, but otherwise no serious side effects were observed. Factor VII concentrate reduced the risk of precipitating circulatory overload associated with the use of plasma and avoids the unnecessary rise of factor II, IX and X which follows prothrombin complex concentrates.


The effects of an increase in endogenous oestrogen on the haemostatic mechanism.

The effects on the haemostatic mechanism of rises in circulating human oestrogen in a group of women being treated for infertility with pituitary hormones were studied. Despite large but brief rises in oestrogen levels no changes were found.


Blood platelets as a possible source of creatine kinase in rat plasma and serum.

The creatine kinase (CK) activity in rat plasma was found to be correlated with that in serum or platelets. Rat serum contained higher activity not only of CK but also of lactate dehydrogenase than the corresponding plasma. The plasma CK activity decreased with increasing age of rats. Only the brain-type isoenzyme of CK was found in plasma, serum and platelets. Contamination of brain-type with muscle-type isoenzyme was detected in rather exceptional cases in which the activity was high among old rats. These results suggest the possible contribution of blood platelets to the CK activity of circulating plasma as well as to the activity in serum in rats.


Creatine phosphate in rat blood platelets.

Creatine phosphate (CP) was found in rat platelets by an assay method devised to increase the specificity and sensitivity. In this method, radioactivity of [14C]ATP was measured after the reaction of CP with [14C]ADP in the presence of creatine kinase. The mean value of the CP content in rat platelets was 24.8 nmoles per 10(9) platelets. Since the molar ratio of CP and ATP was 1:2.6, it is probable that CP plays a role in the energy metabolism of rat platelets.


The role of prostaglandins in the ADP-induced aggregation of rabbit platelets shown by the use of 15-hydroxyprostaglandin dehydrogenase.

The initial shape change and subsequent aggregation of platelets in citrated rabbit platelet-rich plasma caused by ADP in vitro was inhibited by 15-hydroxyprostaglandin dehydrogenase. This inhibition was NAD-dependent and was also seen when shape change and aggregation were initiated by sodium arachidonate or by collagen. The aggregation of gel-filtered rabbit platelets by thrombin was not, however, affected by removal of 15-hydroxyprostaglandins. Indomethacin was found to inhibit ADP-induced aggregation but at a concentration (250 micron) much higher than that required to inhibit collagen-induced aggregation. Moreover the platelet release reaction had not taken place 3 min after ADP stimulation. The direct role 15-hydroxyprostaglandin production in ADP-induced aggregation of rabbit platelets is proposed. The involvement of 15-hydroxyprostaglandins in platelet aggregation caused by other inducers is also discussed.


Plasminogen activator levels in plasma and urine during exercise and oral contraceptive use.

The effect of Demulen (ethinyl estradiol 0.05 mg and ethynodiol diacetate 1 mg) and exercise on the level of plasminogen activators was studied in 25 women (12 controls and 13 contraceptive users). Plasma plasminogen activator level was increased by the use of the oral contraceptive and further increased by exercise. Urine plasminogen activator level was unchanged by the use of Demulen but, in both groups of subjects, was decreased by exercise.


Fibrinolysis in decidual spiral arteries in late pregnancy.

The fibrinolytic activity of the intimal cells of decidual spiral arteries and the syncytium of placental villi was studied by electron microscopy in ten normal full-term human pregnancies using a modification of the fibrin slide technique. Endothelial cells lining the intima of the decidual spiral arteries showed a considerably greater fibrinolytic activity than intimal cytotrophoblast and the syncytiotrophoblast showed no activity. The replacement of endothelial cells by an intimal lining of cytotrophoblast, and the presence of cytotrophoblast in the media, appears to play an important role in the reduction of the fibrinolytic activity of the vessel. This inhibition of fibrinolytic activity in the utero-placental arteries may be the physiological mechanism which controls fibrin deposition in these vessels and on the placental villi.


Health care for pets.

Health care for pets cannot develop satisfactorily without a proper structure. Support for practising veterinarians who provide second- and third-line care will continue to be inadequate unless a structure with built-in financial arrangements is introduced. If practising veterinarians do not pass on the costs of specialist help in full to the owners of pets, this form of service will decrease when the number of veterinarians rises to too high a level. Such a development would also threaten the advance of scientific research with regard to pets.


Cushing's syndrome due to adrenocortical adenoma in a cat.

An 11-year-old spayed cat was presented with clinical signs suggestive of hyperadrenocorticism. Adrenocortical function was assessed by dexamethasone suppression and by stimulation with ACTH and the results provided a tentative diagnosis of adrenocortical tumour. Via laparotomy (paracostal approach), the enlarged right adrenal gland was removed. Histopathological diagnosis was adrenocortical adenoma.


Cryosurgery of eosinophilic ulcers in cats.

The use of cryosurgery in treatment of eosinophilic granuloma in cats is described. Satisfactory results were obtained in 14 of 19 cats and 4 of the 5 cats which did not respond favorably, had multiple lesions. The simplicity of the technique and the rapidity of healing make cryosurgery a useful alternative to previous methods of treatment.


Hemodynamic and metabolic consequences of hemodilution with different diluents.

Hemodilution was performed with the crystalloid Ringer's lactate (n = 6) and the colloid Haemaccel (n = 5) in dogs during automatically controlled total cardiopulmonary bypass with constant arterial and venous pressures. Single observations were made with Macrodex and Rheomacrodex hemodilution. Hemoglobin concentration and hematocrit were used as parameters for hemodilution. Total plasma protein proved to be unsuitable. The volume needed to induce the same level of hemodilution with lactated Ringer's and Haemaccel was twice the volume needed with Macrodex and Rheomacrodex. The volume shift from intravascular to extravascular was larger during Ringer's lactate hemodilution than during Haemaccel hemodilution. The amount of volume shift was clearly related to changes in colloid osmotic pressure. Lowering of total peripheral vascular resistance, with increased arterial line flow during controlled constant arterial and venous pressures was seen during hemodilution with each of the above materials. Potassium and calcium concentrations in the blood increased significantly during hemodilution with Haemaccel. Base excess was constant during hemodilution with lactated Ringer's but decreased in all other cases. A decrease in oxygen consumption was common, and most pronounced during hemodilution with Haemaccel.


The clinical refractometer: a useful tool for the determination of specific gravity and osmolality in canine urine.

For the determination of specific gravity of canine urine the urinometer is often used. An alternative method is based on refractometry. Both methods were compared and a table for converting refractometer values to urinometer values is given. The refractometer was also compared with an osmometer. A linear relation was found between the readings of both instruments. The results clearly indicate that the refractometric method is very suitable for the small animal practitioner. The instrument appears to be a good alternative for both the urinometer and the osmometer.


Esophageal squamous cell carcinoma in two cats.

Esophageal carcinomas in two cats are described. The main clinical sign was regurgitation of food and fluids. Radiographic examination revealed severe esophageal abnormalities in both cats. In the second cat, the radiographic appearance of the esophagus together with the esophagoscopic findings provided a presumptive diagnosis of neoplasia. Histologic examination in both cats revealed squamous cell carcinoma with metastases.


Hereditary retinal dysplasia (RD) in a family of Yorkshire terriers.

The clinical, pathological and genealogical features of Retinal Dysplasia in a family of Yorkshire terrriers were studied. The ocular changes were characterized by retinal detachment and retinal neovascularization. Dogs of three litters and their sire were affected. RD was suspected to be inherited as a recessive trait.


Secondary bone tumours: a case report.

Intermittent pain and hyperthermia were the major signs in a ten-year-old male Kerry Blue terrier. Extensive radiologic examination of the skeleton revealed no abnormalities. Gamma camera imaging of the skeleton revealed multiple foci of increased uptake of a bone-seeking radiopharmaceutical. Histologic examination of a bone biopsy provided a tentative diagnosis of osteomyelitis. Therapy with antibiotics was not successful. At autopsy, anaplastic carcinoma was found in the liver, spleen, several lymph nodes, ribs, both humeri, both femurs and almost all vertebrae.


Urovagina associated with female pseudohermaphroditism in four bitches from one litter.

Four littermates with pseudo-hermaphroditismus ovarialis are described. Each had passive urinary incontinence caused by a urovagina. Clinical and radiographic examination and the surgical treatment are described. Results, follow-up and etiology are discussed.


Exfoliative cytology in the diagnosis of diffuse mesothelioma in the dog. Illustration by a case report.

This report deals with a dog which was presented for ascites that appeard to be related to fluid accumulation in the pericardium. Subsequent to resection of the pericardium the ascites disappeared but a few months later there was fluid accumulation in the thorax. Cytological examination of the thoracic fluid revealed the cell aggregates ("cell balls") which are indicative of mesothelioma and this diagnosis was confirmed by the autopsy findings. The initial cytological diagnosis on the pericardial fluid, which was not in agreement with the histology of the excised pericardium, is also discussed.


Heartworm infected dogs in the Netherlands.

Heartworm infected small animal patients are seldom seen in the Netherlands, because the parasite's life cycle cannot be completed in this climate. We report here four cases of the disease in dogs brought to the Netherlands from endemic heartworm areas. The initial diagnosis was based upon this knowledge and clinical signs (low exercise tolerance and coughing). The diagnosis was confirmed by the radiographic finding of variable pulmonary artery enlargement, the electrocardiographic finding of right ventricular hyperptrophy and the presence of microfilariae in the peripheral blood. Treatment resulted in recovery in three of these patients but the fourth died soon after initiation of the therapy.


Quantitation of lysozyme in the urine of the dog for the diagnosis of proximal tubular damage in renal disease.

The serum and urine LZM levels were determined with the lysoplate assay in 26 normal experimental dogs and in 21 dogs with various renal diseases. In the dogs with decreased glomerular filtration the serum LZM levels were higher than in normal dogs (less than or equal to 1.3 mg/l). No LZM could be demonstrated in the urine of normal dogs. The presence of LZM in urine was associated with proximal tubular damage, which indicates that LZM-uria can be used as an index of renal tubular damage.


Pyogranulomatous swellings in the submandibular region of the dog, caused by Actinomyces spp.

Seven dogs with actinomycotic submandibular abscess, probably caused by penetrating wounds in the oral cavity, are described. Antibiotic treatment alone, or in combination with paracentesis, failed in all cases. Recurrences and dissemination were avoided in five of the seven cases by complete removal of the abscess, long-term drainage, flushing with 1% Polyvidon iodine and long-term antibiotic treatment. The main difficulty was a poorly defined margin of the abscess; this made complete removal impossible in three cases. In two of these there were recurrences, but in the third there was complete healing after the second treatment.


[Conditions of management and the construction of piggeries on pig-fattening farms as factors in the incidence of diseases of the lung and liver in slaughtered pigs (author's transl)].

All pigs passing along the slaughter-line in the slaughter-house of the Livestock and Meat Board of the Christian Farmers' Association of the Province of North Brabant are examined for the presence of lesions of the lung and liver. The proportions of animals without any severe lesions of the lungs and livers and the proportions of those with affected lungs, affected livers, condemned livers and pleurisy are reported every three months. Under the Animal Health Service of the Province of North Brabant, investigations were carried out on 251 farms with less than 10 per cent and 251 farm with more than 25 per cent of the animals with severe lesions of the lungs to study the effect of conditions of management on the incidence of diseases of the lung and liver. Among others, this produced the following results:--The average proportions of affected livers and those of the proportions of cases of pleurisy were higher, whereas the daily growth rate of each pig and the carcass quality were lower.--Slaughtered pigs with lesions of the lung and/or liver showed a significantly smaller daily growth rate during the fattening period. In pigs with pleurisy, retardation of growth was also observed on the breeding farm.--The proportion of affected lungs and livers is significantly affected by a number of factors on the farm. Among others, the following factors were found to be of importance: adopting the all in--all out system, removals, the origin of the piglets, the number of pigs in each compartment of the pig house and the construction of the piggery (width of pig house and slatted floor). Taking these factors into account, a "transverse housing system" is recommended.


[Salmonella in scrapings from meat vans (author's transl)].

Throughout a period of thirteen years (from 1965 to 1977 inclusive), samples of scrapings from meat vans were examined weekly for the presence of Salmonella. Samples were collected from the vans on the precincts of the public slaughter-house in Groningen. Of the total number of 6,751 samples studied, 213 (3.16 per cent) were positive for the presence of Salmonella. During the period from 1965 to 1970, the proportions of contaminated samples gradually decreased from 4.85 to 1.11 per cent, whereas it increased again up to 6.33 per cent in 1976. There was a limited seasonal effect on contamination of the scrapings with Salmonella, the highest rates of contamination being recorded during the period from May to October inclusive (warm and humid season). The serotypes most frequently isolated on examination were S. typhi-murium, S. brandenburg and S. panama. These serotypes were also constantly found to be present in other material such as samples of minced meat and scrapings from slaughter-house and butcher's shops. It is concluded that contaminated meat vans are a factor in maintaining cycles of contamination by Salmonella organisms in a rather large area.


[Some aspects of veterinary education, viewed in the light of alterations of structure and renewal of programmes (author's transl)].

Attention having been paid to various aspects of the rapid expansion which scientific education has shown during the past few decades, the various structural changes in veterinary education are discussed. A number of methods are suggested, which may help in attaining the objectives.


HLA and thyrotoxicosis (Graves' disease) in Chinese.

HLA locus A and B typing was performed on 86 Chinese thyrotoxicosis (Graves' Disease) patients and 238 normal Chinese subjects. The frequency of HLA-Bw46 (Sin 2) was found to be significantly higher among the patients than controls (x2 = 26.15, corrected P less than .003, relative risk = 3.74). The risk associated with Bw46 was reflected in the Bw46 heterozygotes. The relative risks of the joint occurrence of Bw46/B40 and Bw46/B13 were 8.74 and 5.88 respectively.


Alzheimer's disease and HLA.

Thrity-four unrelated patients with Alzheimer's disease were typed for HLA-A, -B and -C serological determinants. HLA-Cw3 was increased over control antigen frequencies. This difference lost significance when corrected for the number of antigens tested.


HLA-A, -B, -C and -D antigens in male patients with myasthenia gravis.

HLA-A, -B, -C and -D antigens were determined in 54 male Myasthenia Gravis patients. A significant increase of the B8 antigen frequency was found among patients with an onset of the disease before the age of 35. No significant increase was found among the D antigens. In a combined male and female material with an early age at onset, thymic hyperplasia was correlated to the presence of HLA-B8.


HLA and glioma.

HLA typing of 80 glioma patients was determined and the antigen frequencies were compared with 176 normal controls. Increased phenotypic frequencies of Bw35 and DRw1 were observed, but when P values were corrected by the number of antigens tested (35), the results were no longer significant.


The affected sib pair IBD distribution for HLA-linked disease susceptibility genes.

The distribution of identity by descent (IBD) scores for sib pairs affected with a disease determined by a disease susceptibility (DS) locus tightly linked to the HLA complex is derived. It is shown that the sib pair IBD distribution differs from its a priori distribution and, moreover, is completely specified by three observable population parameters--the additive and dominance variances and the prevalence of the disease in the population. An application of the model is illustrated using data on juvenile diabetes mellitus.


Secretin-like bioactivity in the duodenal mucosa in patients with peptic ulcer and chronic pancreatitis.

Biopsy specimens of the duodenal mucosa were assayed to determine their secretin-like activity in 9 controls, 9 patients with gastric ulcer, 19 patients with duodenal ulcer, 4 patients with gastric and duodenal ulcer, and 13 patients with chronic pancreatitis. The bioassay of secretin was done on the pancreatic secretion in anesthetized rats. The sensitivity was in the orcer of 0.0625 CHR unit/rat (4 ng/rat). In the range between 0.0625 and 0.5 CHR units a satisfactory dose dependency was recognized. The following results were obtained. 1) The level of duodenal mucosal secretin-like activity in patients with gastric ulcer was the same as that in the controls, but was elevated in 32% of the patients with duodenal ulcer, 50% of those with gastric and duodenal ulcer, and 8% of those with chronic pancreatitis. 2) The high level of secretin-like activity noted in patients with duodenal ulcer was suspected to be related to the hypersecretion of gastric acid which is characteristic of this disease, but there was no correlation between gastric acid secretion and secretin-like activity in the duodenal mucosa.


Age-related changes of glomerular basement membrane in normal rats.

The structural changes of the renal glomeruli in development and aging were investigated by electron microscopy in normal rats from 4 to 36 weeks of age at 4 weeks intervals after birth. Infantile rats had an uneven glomerular basement membrane which was characterized by double-layered or mossy appearances of the lamina densa. On the other hand, diffuse and hemispherical thickenings of the basement membrane were observed in older rats. These thickenings were due to the accumulation of basement membrane materials on the epithelial side of the lamina densa. In the older rats, laminae rarae interna and externa were extremely thin. Epithelial cells of the young rat had abundant cytoplasmic organelles and relatively electron-lucent secretory bodies, whereas those of the older rat had less numerous cytoplasmic organelles, many myelinated bodies suggesting autophagosomes, and electron-dense whorl-formed secretory bodies. Mesangial regions of the young rat took small parts of the glomeruli and loosely contacted with endothelial cells. With increasing age, the mesangial matrix also took a greater part of the mesangial regions. The most even figure of the basement membrane was observed in 12 to 16 week old rats.


Increased weight and protein contents of the aorta and left ventricle in acute Goldblatt hypertension.

The weight and protein contents of the aorta and left ventricle were measured in rabbits with two-kidney or one-kidney Goldblatt hypertension (group 2H and group 1H) and in respective control animals (group 2C and group 1C). 14 days after a renal artery constriction the protein contents of the aorta were greater in group 2H (124+/-3 mg) than in group 2C (95+/-2 mg) (p less than 0.001) and in group 1H (124+/-5 mg) than in group 1C (102+/-4 mg) (p less than 0.001). The weight and protein contents of the aorta and of the left ventricle were also significantly greater in group 1H and group 2H than in group 1C and group 2C respectively. Furthermore in both types of hypertension the weight and protein contents of these two organs significantly correlated to the blood pressure. These results indicate that hypertrophy of the aorta as well as the left ventricle develops already in early developing stage of Goldblatt hypertension.


Quantitative estimation of age-related thickening of glomerular basement membrane in normal rats.

Constant age-related increases in the width of glomerular basement membrane of normal rats were ascertained by quantitative estimation on electron micrographs. The thickness of glomerular basement membrane associated with aging was expressed by a regression equation; Y=0.03X+0.96 (Y, thickness of the glomerular basement membrane in 10(3) X A; X, rat's age in weeks), and the correlation coefficient between age and basement membrane thickness was very high (r=0.95). Standard deviation of the average thickness of glomerular basement membrane also increased with aging. Individual variation in various age groups was large in the infantile and older groups, while it was smallest in the group of 16 weeks of age. Frequency distribution curves of the thickness of basement membrane in the infantile and young rats were steep, whereas those in the older rats were blunt. The peak of curves of the older rats shifted to the right.


Long-term fate of [14C]nicotine in the mouse: retention in the bronchi, melanin-containing tissues and urinary bladder wall.

N-methyl-14C and 2'-14C-labelled nicotine were used for whole-body autoradiographic distribution studies on C57BL- and NMRI-mice. Radioactivity was retained in the melanin-containing tissues, in the bronchial walls, and in the urinary bladder wall, up to 1 month after administration. The activity levels in the bronchi decreased faster if [2'(14)C] nicotine was used. Quantitative measurements of the retention of the 2 14C-labelled nicotine preparations confirmed the autoradiographic findings. It is proposed that nicotine is N-demthylated in the bronchial mucosa, the off-coming methyl group being incorporated into the cell constituents of the mucosa. Thin-layer chromatographic studies showed that no nicotine was present in the lungs after 24 h. In melanin, however, only unmetabolized nicotine was found from 4 h on. Some reactive nicotine metabolites may be responsible for the retention in the urinary bladder wall. Also in the full-term fetuses radioactivity accumulated in the pigmented eyes and in the respiratory tract. The accumulation and long-term retention of nicotine in the melanin-containing structures might accelerate the development of drug-induced or senile changes in these tissues. The retention in the urinary bladder wall persisted even after rinsing. This may indicate an accumulatory mechanism worth considering in the pathogenesis of urinary bladder cancer.


[Action of detergent products in the aquatic larvae of Chaoborus and Cloen: importance of their physiological activity (author's transl)].

For the Chaoborus larvae (Diptera), the toxic effect of detergents depend on their physiological activity: the diapausing animals are less sensitive. On other respects, the speed of this effect is linked to the chemical composition of the detergents. For the Cloeon larvae (Ephemeroptera) these products seem to interfere with the molting process: some of them induce a decrease in the molting frequency, others are without effect; on the other hand a commercial washing powder induces a real increase of this frequency.


Inhalation toxicity studies on cigarette smoke (VI). 6-week comparative experiments using modified flue-cured cigarettes: histopathology of the lung.

Rats were exposed twice daily for 6 weeks to diluted smoke derived from cigarettes with a range of deliveries of particulate matter. The inhaled smoke reached the alveolar surface, increased the size and number of free macrophages and provoked epithelial metaplasia but did not appear to alter the lymphoid reaction to spontaneous infection. The hypertrophy of the macrophages was typically alveolar and their hyperplasia was directly proportional to the particulate delivery of cigarettes smoked. Alveolar metaplasia was incipient, developed characteristically near the respiratory bronchiole in close association with macrophage clusters and only in rats exposed to smoke from cigarettes with the highest delivery of particulate matter.


Inhalation toxicity studies on cigarette smoke (VII). 6-week comparative experiments using modified flue-cured cigarettes: histopathology of the conducting airways.

Rats were exposed twice daily for 6 weeks to diluted smoke derived from cigarettes with a range of deliveries of particulate matter. The inhaled smoke caused squamous metaplasia and keratinising hyperplasia in the larynx and goblet cell hyperplasia in the nasal cavity, trachea and intrapulmonary bronchus. Squamous metaplasia occurred in the larynx of almost all rats exposed to smoke but never in their tracheas or bronchi. The degree of reaction observed for the other responses, except goblet cell hyperplasia in the trachea, was positively related, by quantitative microscopy, to the particulate delivery of cigarettes. These findings, together with other smoke-induced changes which occur in the pulmonary alveoli, provide a basis for the short-term bioassay of inhalation toxicity of cigarette smoke.


Increased carbon tetrachloride hepatotoxicity after low-level ethanol consumption.

Male rats provided with a 5 or 15% (v/v) ethanol solution as the sole source of fluid consumed ethanol at a rate of 11.4 or 24.9% of total calories (4.2 or 8.3 g/kg daily). After ethanol consumption lasting 1, 2 and 3 weeks the hepatotoxicity of CCl4 (0.1 ml/kg i.p.) was elevated by determination of serum activities of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase ( GPT), sorbitol dehydrogenase (SDH) and histological investigations. Carbon tetrachloride (CCl4)-induced liver damage was significantly greater in rats provided with ethanol than in the tap-water consuming controls. This potentiation of CCl4 hepatotoxicicty was fully developed already after a 1-week exposition to ethanol and was greater in the 15% than in the 5% ethanol group. Ethanol alone did not influence serum enzyme activities but increased microsomal aniline hydroxylation. There was, however, no clear-cut parallelism between potentiation of CCl4 hepatotoxicity and activation of aniline hydroxylation.


Long-term toxicity of diethyl carbonate in mice.

Groups of 48 male and 50 female mice were given drinking-water containing 0, 50, 250 or 1000 ppm diethyl carbonate for 83 weeks. There was no effect on mortality, rate of body-weight gain or the incidence of histopathological findings, including tumors. There were isolated differences between treated and control mice in the findings of the haematological examinations and in the liver weights of female mice but these were not considered to be related treatment. It is concluded that no carcinogenic effect could be detected and that the no-untoward-effect level is 1000 ppm (approx. 140 mg/kg/day).


Effects of vinyl chloride exposure alone and in combination with trypan blue--applied systematically during all thirds of pregnancy on the fetuses of CFY rats.

Vinyl chloride (VC) has been shown to be present in the fetal and maternal blood as well as in the amniotic fluid after the exposition of pregnant CFY rats to VC at an atmospheric concentration of 5500, 18 000 or 33 000 mg/m3 (approximately 2000, 7000 or 12 000 ppm) for 2.5 h on the 18th day of pregnancy, indicating the permeability of the placenta to the agent. Teratological investigation of the offspring of pregnant rats exposed continuously to VC at an atmospheric concentration of 4000 mg/m3 air (1500 ppm) during the first, second or last third of pregnancy has shown that VC has no teratological effect in the rat and has no embryotoxic effects either, when applied during the second or last third of pregnancy in the above concentration. Exposition to VC during the first third of pregnancy resulted in an increased fetal mortality and in the manifestation of embryotoxic effects. Fetal losses and induction of central nervous system malformation due to trypan blue administration were not potentiated by a combined exposure of pregnant rats to VC and the dye.


Embryotoxic effects of benzene and its methyl derivatives: toluene, xylene.

CFY rats were exposed to inhalation of 1000 mg/m3 (313ppm) benzene, 1500 mg/m3 (399 ppm) toluene, or 1000 mg/m3 (230 ppm) xylene for 24 h/day from day 9 to day 14 of pregnancy; to that of 1500 mg/m3 (399 ppm) toluene for 24 h/day from day 1 to day 8 of pregnancy, or 1000 mg/m3 (266 ppm) toluene for 8 h/day from day 1 to day 21 of pregnancy,. CFLP mice were exposed to inhalation of 500 mg/m3 (133 ppm) toluene for 24 h/day from day 6 to day 13 of pregnancy. Untreated animals and groups inhaling pure air served as controls. None of the solvents proved to be teratogenic, the incidence of malformations did not change as a result of exposure, though an increase in skeletal anomalies (extra ribs, fused sternebrae) was observed with all 3 solvents. Benzene and toluene also caused considerable retardation of fetal development. The growth retarding effect of toluene on fetal development in early pregnancy is of particular importance from the point of view of occupational hygiene.


Effects of chronic inhalation of dimethyl ether in the rat.

Dimethyl ether (DME) is a colourless gas with an ethereal odour. It is used mainly as a liquid refrigerant and an aerosol dispersant. Little or no data exist on the toxicology of this material. In the present study, groups of male and female rats were exposed to 0.02%, 0.2% and 2% v/v of DME in air, 6 h/day, 5 days/week for 30 weeks. At the end of the study the high-dose level male rats showed a significant reduction on liver weight compared with the control group; this was accompanied by raising SGPT levels. In high-dose female rats there was no significant effect on liver weight but the SGPT levels were raised above control values. No histological abnormalities were observed in the liver or in any other organ.


[Experimental differentiation in animals of oral and inhaled lead burden from combined absorption of industrial emissions].

Trials in sheep and rabbits were performed in an area of industrial immissions in the summer months of 1974--1976, to differentiate oral and inhalative lead actions. The animals lived at different distances and in different directions from a lead emitting factory. Hematological and biochemical assays showed that only the measure of the activity of aminolevulinic acid dehydratase produces most significant results of the inhalative influences of lead. To state effects after oral ingestions the estimation of ALA-D and of free erythrocyte porphyrines were suitable. The inhalation of air with lead content between 2 and 14 micrograms/m3 reduced the activity of ALA-D, if the lead content of feed did not exceed the value of 35 ppm. After feeding a lead concentration of more than 35 ppm, the influence of the inhalative action was superposed by the action of the oral intake. The inhalative action can only be demonstrated after a low oral intake. The results indicate that inhalative actions of lead can be proven in an open field area around a lead emitting factory.


Measurement of fecal bile acid excretion in gnotobiotic rats: comparison of gas-liquid chromatography and [4(-14C)] cholesterol isotopic equilibrium.

Gas-liquid chromatography (G.L.C.) and the method of [4(-14C)] cholesterol isotopic equilibrium (C.I.E.) were used to determine the fecal bile acid excretion in gnotobiotic rats. The same samples were submitted to both methods. In these conditions, it was observed that the fecal bile acid excretions determined by G.L.C. were 38% of lower than when determined by C.I.E. In thin-layer chromatographic analyses (T.L.C.) of the bile acid extracts obtained from rats in which a [4(-14C)] cholesterol isotopic equilibrium was established, 33 to 35% of the radioactivity of this fraction was not observed in the rat primary bile acids. No bile acids could be observed in G.L.C. made with eluates obtained from the T.L.C. areas containing this radioactivity. It therefore appears that the difference observed in the results obtained by G.L.C. and C.I.E. is due to the fact that chemical species which are not measured by the former method can be determined by the latter one. T.L.C. analyses of bile acid extracts from axenic rats in which either a [26(-14C)] cholesterol or a [2,4(-3H)] cholic acid and [24(-14C)] chenodeoxycholic acid equilibrium were established, lead to the conclusion that the chemical composition of these undetermined substances is complex: part of these substances comes from the transformation of bile acids; another part is made of molecules which maintain the 26(-14C) of cholesterol.


Corticosteroid receptors in the avian kidney.

The binding in vitro of tritiated aldosterone to domestic duck (Anas platyrhynchos) kidney tissue has been investigated. Using tissue from animals on a normal diet, tritiated aldosterone was specifically bound to kidney cytosol with an apparent equilibrium dissociation constant of about 9 nM and number of binding sites in the 20 fmol/mg protein range. These values did not show statistically significant changes when the cytosol originated from animals with salt activated nasal glands. Kidney cytosols labeled with tritiated aldosterone sedimented with a single peak at 8S in a linear sucrose gradient (10--30%) and this peak was quenched by excess, radioinert aldosterone. Following incubation of labeled cytosols with crude nuclei, the cytosols became depleted of the label and aldosterone was translocated to the Tris-soluble and Tris-insoluble, 0.4 M KC1 soluble nuclear fractions. Kidney cytosols metabolized aldosterone extensively to a compound presumed to be 3alpha,5beta-tetrahydroaldosterone. However, only unchanged aldosterone became receptor-bound. It was concluded that the duck kidney possesses aldosterone receptors, though competition studies indicated that the specificity of these receptors might be different from those described in the mammalian kidney.


Angiotensin stimulates cortisol biosynthesis in human adrenal cells in vitro.

Adrenal glands obtained from patients undergoing therapeutic adrenalectomy were used to study the effects of angiotensin on human adrenal steroidogenesis. It was observed that angiotensin stimulated cortisol biosynthesis. Although this has been demonstrated to occur in canine and bovine adrenals, angiotens in-induced cortisol biosynthesis has not been established in man. The possibility that angiotensin merely stimulated glomerulosa cells to secrete precursor steroids which accumulated in the medium and then diffused into fasciculata cells to provide substrate for cortisol biosynthesis was excluded by demonstrating that 3beta-hydroxy-5-pregnen-20-one (pregnenolone) and progesterone (the only pertinent precursors) did not accumulate in angiotensin-stimulated cell suspension. In addition, angiotensin stimulated cortisol biosynthesis in a fasciculata cell suspension in which angiotensin did not stimulate aldosterone production. Therefore, in human adrenal cell suspensions angiotensin appeared to act directly to stimulate cortisol synthesis by fasciculata cells. In normal subjects pre-treated with dexamethasone, angiotensin infusions failed to stimulate an increase in plasma cortisol. The physiological importance of angiotensin as a regulator of cortisol secretion remains, therefore, to be established.


A radioimmunoassay for lithocholic acid conjugates in human serum and liver tissue.

A sensitive and specific radioimmunoassay for glycine and taurine conjugates of lithocholic acid (CLCA) has been developed. 3H-glycolithocholic acid (S.A. = 17Ci/mmol) was used as tracer. Separation of free from antibody-bound bile acid was carried out using ammonium sulphate (saturated solution). The antiserum showed high specificity for both glyco and tauro conjugated lithocholate (100% cross reaction) and lithocholic acid (25% cross reaction). The sensitivity of the assay (1 pmole/tube), was adequate for measuring CLCA in peripheral blood and hepatic tissue in man.


Metabolism of 17beta-hydroxy-2-hydroxymethylene-5alpha-androstan-3-one in the rabbit.

An acidic metabolite, 2alpha-carboxy-5alpha-androstane-3alpha,16alpha,17alpha-triol and two neutral metabolites, 2alpha-hydroxymethyl-5alpha-androstane-3alpha,17alpha-diol, and 2alpha-hydroxymethyl-5alpha-androstane-3alpha,16alpha,17alpha-triol have been identified in the urine of rabbits orally dosed with 17beta-hydroxy-2-hydroxymethylene-5alpha-androstan-3-one. 2alpha-Hydroxymethyl-5alpha-androstane-3alpha,16alpha,17alpha-triol was previously obtained from the urine of rabbits dosed with 17beta-hydroxy-2alpha-methyl-5alpha-androstan-3-one. The acidic metabolite was the major urinary excretion product.


Simultaneous radioimmunoassay of 5alpha-androstane-3alpha, 17beta-diol and 5alpha-androstane-3beta, 17beta-diol unconjugated and conjugated in human serum.

The simultaneous determinations of both 3alpha and 3beta epimers of 5alpha-androstane-3,17beta-diol as their glucuronides, sulfates and in their unconjugated forms are described. The diol estimation is carried out by radioimmunoassay with two specific immune sera after purification of the serum by use of chromatography on Sephadex LH-20. The values obtained (mean +/- S.D.) in pg/ml for the unconjugated 3alpha and 3beta epimers were, respectively, 267 +/- 67 and 816 +/- 76 for men; 114 +/- 33 and 515 +/- 177 for women; 142+/- 77 and 779 +/- 200 for hirsute women. Among the conjugates, the most important were the sulfoconjugates, their rates being, respectively (men +/- S.D. in ng/ml 41.6 +/- 9.5 and 103+/- 40 for men; 12.4 +/- 3.1 and 51.2 +/- 14.9 for women and 36 +/- 22 and 72 +/- 36 for hirsute women. Differences in the conjugation of both epimers were also noticed.


Methoxylation of 3beta,7alpha-dihydroxychol-5-en-24-oic acid, a key intermediate of chenodeoxycholic acid biogenesis, compared with that of its 7beta-epimer.

The conventional methods of gas liquid chromatography or mass spectrometry failed to be useful for the identification of the biliary 3beta,7alpha-dihydroxychol-5-en-24-oic acid, a key intermediate of chenodeoxycholic acid biogenesis. It has been preliminarily reported that this acid in human bile was successfully identified by gas chromatography-mass spectrometry, after the methoxylation of its allyl alcohol group. Physical as well as spectral properties of the methoxylation products derived from the acid were reported, compared with those from its 7beta-epimer.


Further consideration of systematic errors present in protein-ligand interactions.

Relatively minor systematic errors present during measurements of protein-ligand interaction can lead to large inaccuracies in the calculated values of the equilibrium dissociation constant and the total concentration of the binding protein. These errors, which include binding of the ligand to low affinity material and underestimation of bound ligand, cause the calculation of the concentration of free ligand at equilibrium to be overestimated. We report herein a model of ligand-protein binding which incorporates these errors into the mathematical formulation of the equilibrium binding equation. The effect of these errors on the Scatchard plot is presented.


Methoxylation of methyl 3alpha,7alpha-dihydroxychol-4-en-24-oate and its 3beta-epimer. A contribution to chenodeoxycholic acid biogenesis.

By the conventional methods of gas liquid chromatography (GLC) as well as mass spectrometry, 3beta,7alpha-dihydroxychol-5-en-24-oic acid (delta5-acid), a key intermediate of chenodeoxycholic acid biogenesis and its metabolic by-product, 3alpha,7alpha-dihydroxychol-4-en-24-oic acid (delta4-acid) have not yet been identified as such probably due to thermal decomposition. However, taking advantage of the observation that they are readily methoxylated in methanol containing a trace of acids, their individual methoxy-compounds were easily prepared and proved to be useful for their identification, even though they are present in minimal amounts as was the case with the human or hen bile. The present paper reported physical as well as spectral properties of the methoxy-compounds derived from methyl 3alpha,7alpha-dihydroxychol-4-en-24-oate, compared with those of its 3beta-epimer.


Steroid estrogen conjugates in hens' urine II. Identifications of some minor conversion products of intramuscularly injected [4(-14C)]estrone.

[4(-14C)]Estrone was injected intramuscularly into two mature laying Rhode Island Red hens. Radioactive steroids and steroid conjugates recovered from the urine on Amberlite XAD-2 columns were fractionated on columns (100 cm) of DEAE-Sephadex A-25 by NaC1 gradients. The presence of the following were confirmed, the figures in brackets indicating average proportions as per cent of total radioactivity recovered after Sephadex column chromatography:-the 3-beta-glucuronides of estrone (10.9) and of estradiol-17alpha plus estradiol-17beta(9.8): the 17-beta-glucuronides of estradiol-17alpha plus estradiol-17beta (2.1); the 3-sulfates of estrone (14.5) and of estradiol-17alpha plus estradiol-17beta(27.4); and the disulfates of estradiol-17alpha plus estradiol-17beta (2.3). The following additional conjugates were identified:-a beta-glucuronide of 16-epiestriol (0.2) and a beta-glucuronide of 16-keto-estradiol-17beta (0.2); the 3-sulfates of 16-epiestriol (1.4), of 17-epiestriol (0.9), of 16,17-epiestriol (0.7), of 16-keto-estradiol-17beta (1.1), and of 2-methoxyestrone (0.7). Some evidence was obtained for the presence of 16,17-epoxy-estratrienol-3-sulfate (1.9).


Free radicals in cerebral ischemia.

The possibility that cerebral ischemia may initiate a series of pathological free radical reactions within the membrane components of the CNS was investigated in the cat. The normally occurring electron transport radicals require adequate molecular oxygen for orderly transport of electrons and protons. A decrease in tissue oxygen removes the controls over the electron transport radicals, and allows them to initiate pathologic radical reactions among cell membranes such as mitochondria. Pathologic radical reactions result in multiple products, each of which may be present in too small a concentration to permit their detection at early time periods. It is possible to follow the time course, however, by the decrease of a major antioxidant as it is consumed by the pathologic radical reactions. For this reason, ascorbic acid was measured in ischemic and control brain following middle cerebral artery occlusion. There was a progressive decrease in the amount of detectable ascorbic acid ranging from 25% at 1 hour to 65% at 24 hours after occlusion. The reduction of this normally occurring antioxidant and free radical scavenger may indicate consumption of ascorbic acid in an attempt to quench pathologic free radical reactions occurring within the components of cytomembranes.


"Stump" on internal carotid artery--a source for further cerebral embolic ischemia.

A series of 9 patients have experienced hemisphere and retinal ischemia at an interval after occlusion of appropriate internal carotid arteries. All had radiological evidence of a persisting proximal stump to the occluded artery and, in most, pathological evidence of thrombotic material attached to atheromatous lesions within the stump. Thromboembolism from the stump via the anastomotic supply through ipsilateral common and external carotid arteries is thought to be responsible for the ischemic events to the brain or retina despite absence of flow through the internal carotid artery. Seven of the 9 were treated by surgical excision or obliteration of the stump and, when indicated, common and external carotid endarterectomy. Turbulence in the stump contributed to progressive atherosclerotic changes and probably aggravated thrombogenesis in this location with subsequent embolization into the anastomotic arteries.


Intracerebral hemorrhage following carotid endarterectomy: a hypertensive complication?

Two patients with transient ischemic attacks and subsequent minor cerebral infarction had repair of very tight carotid stenosis, 4 and 5 weeks respectively after their stroke. Each developed intracerebral hemorrhage when hypertension was uncontrolled during the post-operative period. Hypertension is a significant complication of carotid endarterectomy, and may be a prominent factor in the development of intracerebral hemorrhage post-carotid endarterectomy.


Imaging the carotid bifurcation using continuous-wave Doppler-shift ultrasound and spectral analysis.

A non-invasive method is described for visualizing the carotid bifurcation using a continuous-wave Doppler-shift technique simultaneously with spectral analysis of the blood velocities from all parts of the vessel lumen. The system is directional so that arteries can be visualized in the presence of signals from adjacent veins. The technique uses a transducer which is attached to a position-sensing arm so that the position of the ultrasound beam on the neck, when sensing arterial blood flow-velocities, can be translated onto a storage oscilloscope. By repeated passes of the transducer across the vessel lumen a 2 dimensional image of the carotid bifurcation is formed. As each image point is marked, the full spectrum of blood-velocities corresponding to that position is continuously displayed on a second oscilloscope beside the image scope. Ultrasound images are compared with arteriograms and both continuous-wave and pulsed Doppler ultrasound imaging systems are discussed.


Effect of aminophylline on cerebral infarction in the Mongolian gerbil.

The effects of aminophylline in Mongolian gerbils subjected to unilateral carotid ligation were studied. The drug was given in varying intraperitoneal doses at varying postoperative intervals and the animals observed for 5 days for clinical signs of stroke. Doses of 100 mg per kg caused early death and were discontinued. Doses of 50 mg per kg had no significant effect on morbidity, mortality, time until death, stroke incidence or lesion size, as compared to saline given as a control. Doses of 80 mg per kg caused a higher mortality, higher morbidity, and a shorter interval to death, but a smaller infarct. Thus, aminophylline did not have a protective effect against stroke in gerbils and was actually detrimental during the first 16 hours following the carotid ligation.


Effect of DPPD (diphenyl-para-phenylenediamine) on stroke and cerebral edema in gerbils.

Diphenyl-para-phenylenediamine (DPPD) is an antioxidant that has been shown to decrease liver damage due to the peroxidative process of carbon tetrachloride in rats and to ameliorate cold-induced cerebral edema in cats. Because lipid peroxidation disrupts the integrity of the plasma membrane, a process believed to occur in cerebral infraction, which is a major cause of cerebral edema. DPPD was tested for its protective effect against cerebral infarction. When given intraperitoneally in gerbils with unilateral ligation of the common carotid artery, DPPD had no effect on resultant incidence, morbidity, or mortality of cerebral infarction. Despite these findings, the authors believe, on the basis of what is known about free radical pathology, that DPPD and other antioxidants deserve further laboratory trials as possible drugs in the treatment of brain trauma and cerebral edema.


Vasoconstrictor effect of angiotensin on pial arteries.

The effect of topical application of angiotensin on pial arterioles was examined in anesthetized cats equipped with a cranial window for the direct observation of the pial microcirculation of the parietal cortex. Angiotensin in a dose of 0.01 to 1 microgram/ml constricted pial arterioles and arteries strongly. The response of the smaller vessels was greater than that of the larger ones. Intravenous administration of angiotensin in a dose of 0.04--3.8 microgram/min raised arterial blood pressure and constricted the larger pial arteries. While the infusion of angiotensin was continued at the same dose, the blood pressure was then reduced to the control level via bleeding into a reservoir. This abolished the vasoconstriction of the larger pial arteries, showing that this effect was due to autoregulatory adjustments to the rise in blood pressure and not due to a direct effect of angiotensin. We conclude that, despite the strong constrictor effect of angiotensin on pial arteries, intravenous angiotensin can be used to study the effects of arterial hypertension on the cerebral circulation.


Responses of isolated dog cerebral and peripheral arteries to prostaglandins after application of aspirin and polyphloretin phosphate.

In helically cut strips of dog cerebral, coronary, mesenteric and femoral arteries, the contractile response to prostaglandin (PG) F2alpha, and E2, relative to contractions induced by 30 mM K+, did not appreciably differ, whereas relaxations induced by PGE1 relative to those induced by 10(-4) M papaverine were significantly different; the least in cerebral arteries and the greatest in mesenteric arteries. The relaxation of human cerebral arteries in response to PGE1 was similar to that of dog cerebral arteries. Treatment for 60 min with polyphloretin phosphate (3 X 10(-5) and 10(-4) g/ml) suppressed the contractile response to PGF2alpha and E2 but did not alter the response to 25 mM K+. The relaxing effect of PGE1 was not influenced. Aspirin (5 X 10(-5) and 2 X 10(-4) M) significantly potentiated the contractile response to PGF2alpha and E2 but did not alter the relaxation induced by PGE1. In contrast, contractions induced by serotonin were attenuated. It is concluded that dog cerebral, coronary, mesenteric and femoral arteries relaxed differently in response to PGE1. It appears that arterial responses to vasoconstricting PGs, but not to the vasodilating PG, are significantly attenuated by polyphloretin phosphate and potentiated by aspirin.


Cerebral hemodynamics in Shy-Drager syndrome: variability of cerebral blood flow dysautoregulation and the compensatory role of chemical control in dysautoregulation.

Cerebrovascular autoregulation and CO2 reactivity were measured repeatedly in 3 patients with the multiple system atrophy type of autonomic insufficiency (Shy-Drager syndrome) by means of the 133Xe injection method. The degree of cerebral blood flow (CBF) dysautoregulation showed day-to-day variations in 2 of the 3 patients. The CO2 reactivity was normal or supernormal in the supine position in patients with impaired autoregulation. In the head-up position the response to CO2 was slightly suppressed in 2 of the patients, suggesting that chemical control may have tended to compensate for CBF dysautoregulation. It is concluded that the mechanism of chemical control of the cerebrovasculature is different from that which controls autoregulation and may have partially compensated for CBF dysautoregulation.


The spectrum of infection and sensitivity of organisms isolated from African and Indian children in a Durban hospital.

A prospective study was undertaken over a period of six months to determine the spectrum of infection, sensitivity of organisms isolated, and suitability of antibiotics chosen in 520 consecutive patients admitted to a paediatric unit. Culture and sensitivity of stool, urine and blood yielded 752 isolates; in 147 cases, more than one pathogen was isolated from the same or different sites. High rates of resistance to chloramphenicol, ampicillin, and kanamycin were seen in salmonellae other than Salmonella typhi, which differed in retaining its original sensitive susceptibility profile. Most Enterobacteria were sensitive to gentamicin. Penicillin-resistance was seen in 9% of meningococci, and several Haemophilus influenzae strains (20%) were resistant to ampicillin. Methicillin-resistance was encountered in 13% of Staphylococcus aureus strains and 17% of pneumococci were resistant to penicillin G. The sensitivity pattern of organisms isolated was probably directly related to widespread use of antibiotics.


Holter monitoring in patients with transient focal cerebral ischemia.

The value of continuous long-term ECG monitoring in patients with transient generalized neurological symptoms is well established, but its value in transient focal neurological deficits is less clear. A patient is reported who had significant dysrhythmias and transient focal cerebral symptoms which did not clear after cardiac pacing. Nineteen other patients were monitored as part of their evaluation for transient focal cerebral symptoms and were found to have essentially no cerebrally significant dysrhythmias. This report suggests cardiac dysrhythmias rarely cause such symptoms.


Aflatoxin load of common food in savanna and forest regions of Nigeria.

Aflatoxin, one of the most widespread of the known carcinogens, is present at a high level in most common foods stored poorly for long periods in Nigeria. It may work synergistically with other carcinogens to produce the high incidence of primary liver cancer seen in young men under the age of 40. In the northern savanna areas cereals, especially sorghum and millets, as well as groundnut products are the high risk foods. In the southern forest areas, dried fish, groundnuts and oil palm products often carry unwholesome quantities of aflatoxin. Public health measures aimed at reducing the aflatoxin load in high risk foods identified should now be actively considered.


Serological and clinical investigations of human hydatid case in Libya.

Fifty surgically confirmed cases of hydatid disease in Eastern Libya were investigated. Of these, 30 had cysts of the liver, five had extra-hepatic abdominal cysts and 15 had cysts in the chest, including the lungs. Ten cases of malignancy of the liver and five cases of malignancy of the lung were used as controls. Differential diagnosis of cancer was made by measuring the ESR and glycoprotein levels (elevated x 4 and x 3 respectively, in cancer cases). Serum bilirubin, SGOT, SGPT and serum alkaline phosphatase levels were also significantly raised in malignancy, while the total protein levels and eosinophilia were the same in both diseases. The intradermal test was positive in 88%, the haemagglutination test in 86% and the complement fixation test in 70% of cases. In the post-operative follow-up, complement-fixing antibodies disappeared somewhat faster than did the haemagglutinins. The positive skin test cases, however, remained positive throughout the 12-month follow-up period.


Unusual axonemal doublet arrangements in the flagellum of Leishmania amastigotes.

Studies on the fine structure of Leishmania mexicana, L. enriettii and L. tropica major have revealed several unusual arrangements of microtubules in the flagellar axoneme. The anterior end of the flagellum in these three species was found to contain disarranged axonemal doublets (d) in the absence of the two central singlets(s). Leishmania amastigotes do not use their flagellum as do promastigotes for propulsion, and persistence of the usual 9d and 2s microtubular arrangement may not be necessary.


The use of ABO blood groups as markers for mosquito biting studies.

Discrepancies between malaria inoculation rates measured entomologically and parasitologically may be explained, at least in part, if infants and children receive less mosquito bites per night than do adults. We found that this problem could be studied by choosing women and children of different ABO blood groups. In preliminary laboratory studies it was found that the blood group of a mosquito's blood meal could be determined in parous and nulliparous mosquitoes for at least 24 hours, and, nullipares up to 34 hours, after feeding. An antiserum against the O group was necessary to distinguish non A or B red cells from those of animal origin. Cross reactions did occur, presumably as a result of the digestion by mosquitoes of the red cell surfaces, but in every case the strongest and earliest developing agglutination was that of the host. Field studies were made using women and children sleeping under mosquito nets, the holes in which made the nets a trapping device. The women, on average, received over seven times more bites per night than did the children. The migration of blood-fed mosquitoes from one net to another was negligible.


Variation in delayed hypersensitivity in onchocerciasis.

Soluble antigen preparations were made from Onchocerca volvulus adults recovered from subcutaneous nodules, and from Necator americanus third-stage larvae. Intradermal skin tests were carried out on a total of 100 individuals clinically classified as having either the generalized form of onchocerciasis (86 cases, or the localized sowda form (14 cases). 91 of the people studied produced immediate reactions to the onchocercal antigen, but only those with sowda showed delayed reactions, though one person with generalized disease showed a doubtful delayed reaction. Reactions to N. americanus antigen, both immediate and delayed, were seen in both forms of the disease. The lack of delayed skin reaction in the generalized form of onchocerciasis is discussed, and a comparison is made with other diseases. Preliminary evidence for the existence of a true spectrum of clinical and immunological forms of onchocerciasis is suggested by one case in this study.


Immune complexes in healthy Nigerians.

Sera from 50 healthy Caucasians resident in Britain and 50 healthy Nigerians living aroung Zaria in Northern Nigeria were tested for the presence of circulating immune complexes by three different methods. Immune complexes could not be detected in the Caucasian sera but wer present in the Nigerian sera. However, only six of the 38 sera positive for complexes by the radio-bioassay method had significant anti-complementary activity. Examination of blood films from all six subjects showed malarial parasitaemia in five. The mean IgM level of the six anti-complementary sera was significantly higher than in the remaining 44 sera. After six weeks of malarial prophylaxis, sera from four of these subjects lost their anti-complementary activity and there was a parallel fall in the serum IgM values, suggesting that complexes related to malaria may have been present originally. Tests for detecting circulating immune complexes which fix complement may be useful in identifying clinically significant infections in apparently healthy Nigerians.


Schistosoma japonicum-type infection in Malaysia--report of the first living case.

The first living patient with a Schistosoma japonicum-type infection who presented with the nephrotic syndrome is reported in detail. It is not clear whether the nephrotic syndrome was due to the schistosome infection or to the deposition of hepatitis B antigen and antibody complexes. This is the tenth case of schistosomiasis reported from aborigines in Malaysia and a sylvatic source of infection is suggested.


The resistance of Trypanosoma congolense, T. vivax and T. evansi to human plasma.

Tests were made in mice on the resistance of cattle trypanosomes to human plasma. 12 stocks of Trypanosoma, congolense were tested' three were fully resistant, eight were moderately or highly resistant, and one was fully sensitive. Four stocks of T. vivax were tested; two were fully resistant, one was somewhat resistant, and one was highly sensitive. Two stocks of T. evansi were tested; both fully sensitive. The possibility is discussed that T. congolense and T. vivax might produce transient infections in man.


Single dose doxycycline therapy for scrub typhus.

A single dose of 200 mg of doxycycline was shown to be as effective as a seven day course of tetracycline, in patients suspected of having scrub typhus. 65 (44%) of the 149 patients studied fulfilled the criteria for definite diagnosis of scrub typhus; 10 had an additional diagnosis. Rickettsia tsutsugamushi was isolated from 49 (75%) patients. There was no difference between the two treatment groups in time to defervescence, abolition of cough and headache, or in the time taken to recover well-being. There were no relapses in either group. Of the remaining 84 patients, a causal diagnosis was achieved in 52. Irrespective of a diagnosis there was no difference in apparent response to either doxycycline or tetracycline.


Methods of assessing factor VIII content of stored fresh frozen plasma intended for preparation of factor VIII concentrates.

Minimally destructive methods were sought to assess the factor VIII content of fresh frozen plasma intended for large-scale fractionation and stored in five-liter polyethylene packs after pooling approximately 23 plasma donations. Although factor VII distribution in the frozen pack was not perfectly homogenous, a central "core" through the frozen pack gave a representative sampel of the entire contents of the pack. Coring was compared with other methods of pack sampling before large-scale cryoprecipitation. The survival of factor VIII was studied in three grades of stored plasma which had been separated and frozen within 4 hours, 8 hours, and 18 hours of blood donation. Plasma frozen after overnight storage of blood is a satisfacory starting material for the preparation of factor VIII and factor IX concentrates.


An aseptic fluid transfer system for blood and blood components.

A device is described which can be attached to all blood bags. Two of these devices are heat-sealed together aseptically at any time during the storage life of the blood unit, and an opening connecting the two is created. In vitro and in vivo studies show that ten passes of a unit of blood through these devices produces no cytological changes and does not alter the in vivo survival of the unit when transfused. Further, if the unit is frozen, then thawed, and even stored at 4 C for five days after thawing, the in vivo survival is still unaffected.


The accumulation of mono-2-ethylhexylphthalate (MEHP) during storage of whole blood and plasma.

The accumulation of the plasticizer di-2-ethylhexylphthalate (DEHP) in blood and blood components has been of considerable concern for some time. We have followed the accumulation of DEHP and one of its major metabolities, mono-2-ethylhexylphthalate (MEHP) during storage of whole blood, platelet-rich plasma, platelet concentrates, and platelet-poor plasma for periods ranging from 72 hours to four weeks. Both phthalates showed a progressive increase in concentration with time. While the levels of DEHP were much greater than those of MEHP, there was nonetheless a significant and continual increase in MEHP in all preparations. The highest concentrations of both DEHP and MEHP were found in the platelet-poor plasma, indicating that platelets do not have a major role in the accumulation of the phthalates in blood. The accumulation of MEHP was shown to be a direct result of the metabolism of DEHP by plasma protein(s) rather than leaching from the blood bag.


Recruitment cost: a middle ground between "free blood" and the nonreplacement fee.

Blood banking usually is considered to be clearly divided into two opposing philosphies concerning volunteer donor recruitment. On one side is the "community responsibility" theory. On the other side is the "individual responsibility" theory. This paper will show that both systems have problems and that in practice neither is "pure." We propose a new system that is an effective compromise and that has been successful in the Houston region.


Massive transfusion during major surgery in a child with anti-Knopsa and one kidney.

Massive transfusion has been defined as the replacement of one-third to one-half of the blood volume of the patient. It usually implies the presence of shock and is associated with multiple traumatic injuries. Blood replacement is almost always banked blood given in large quantities. However, massive transfusion with autologous blood can also be applied to elective cases and is becoming a useful and clinically beneficial service both in the quality of the products transfused service both in the quality of the products transfused and avoidance of diseases transmitted by blood transfusion from heterologous blood donor sources. Operations which regularly require the transfusion of three or more units of blood include open heart surgery, orthopedic reconstructive procedures, vascular surgery and abdominal surgical procedures. The case presented here, an orthopedic procedure, describes an example of elective massive transfusion, successfully performed in the presence of a rare alloantibody to red blood cells.


A new antigen, McCa (McCoy), and its relationship to Kna(Knops).

The antigen McCa is detected in 98.5 and 96.7 per cent of the American Caucasian and Negro populations respectively. In population studies with anti-McCa and anti-Kna, a strong association was demonstrated between the two antigens, with 53 per cent of McC(a-) sample being Kn(a-) compared with a reported frequency for Kn(a-) of only 0.19 per cent.


Weak B antigen in a family.

A family is described in which six members were of a week subgroup of B. Presence of the subgroup in each individual was first indicated by lack of anti-B in that person's serum. Additional tests showed that the B subgroup red blood cells would adsorb anti-B and yield that antibody on elution, and that the saliva of two B subgroup persons tested contained B and H substances. The blood of one of the family members with the weak B antigen was inadvertently transfused to a group O recipient but caused no ill effects.


A safe blood transfusion procedure for immunization against major histocompatibility complex determinants in man.

A standardized procedure is proposed for deliberate immunizations against human major histocompatibility complex determinants. The data presented demonstrate its effectiveness and, by using a number of necessary precautions, this procedure has proven to be very safe. The following points are especially important: (1) exclusive utilization of regular blood donors as immunizers; (3) use of whole blood as an immunizing agent; and (3) use of small immunizing stimuli rather than large transfusions. This procedure can be recommended for the production of monospecific anti-HLA antisera and it may be useful if and when a deliberate transfusion policy for prospective kidney recipients is adopted.


Further studies on the relationship of anti-Ena and anti-Wrb in warm autoimmune hemolytic anemia.

The red blood cell eluates of two patients with warm autoimmune hemolytic anemia (AIHA) were found to have anti-dl and anti-Wrb in a study of 150 individuals with positive AHG tests.7 In that series 39 per cent of AIHA cases had anti-Wrb as part of the autoantibody specificity. The eluates of these two patients were of further interest since they showed weaker reactions with En(a-) cells than with En(a+), Wr(a+b-) cells. Further absorption of the eluates confirmed a second component that reacted with the En(a+), Wr(b-) cells but not the En(a-) cell, interpreted as autoanti-Ena. In one of the cases anti-Ena was recovered from the En(a-) absorbing cell although these cells were not agglutinated by the autoantibody. This effect was not due to polyagglutinability, the Matuhasi-Ogata phenomenon or the decreased sialic acid content of the En(a-) red blood cell membranes and remains unexplained.


Particulate material in antihemophilic factor (AHF) concentrates.

Antihemophilic factor (AHF) concentrates contain noncellular particulate material which is retained by a screen filter of 40 mu pore size. This material is composed in part of IgG, fibrinoprotein, and cold insoluble globulin. The clinical significance of this material is uncertain, but a possible association with pulmonary and cerebral microemboli is suggested.


Comparison of sacks and a new colloid hyperosmolar solution for hypothermic renal storage.

A new colloid hyperosmolar solution with high concentrations of proteins, potassium, and glucose has been favorably compared with a crystalloid, intracellular, and hyperosmolar solution (Sacks II) for 24-hr hypothermic storage of ischemic and nonischemic canine kidneys. Sixty minutes of warm ischemia was overcome by all kidneys flushed with the colloid hyperosmolar solution. In four of six ischemic kidneys flushed with Sacks' solution the function returned to normal limits. Hypothermic storage (24 hr) without warm ischemia did not cause any deleterious effects on either one of the flushed group of kidneys. Thirty minutes of warm ischemia followed by 24-hr hypothermic storage was tolerated by most of the kidneys (83%) flushed with the colloid hyperosmolar solution and one-half of the kidneys flushed with the crystalloid hyperosmolar solution. Sixty minutes of warm ischemia and 24-hr hypothermic storage was detrimental to 50% of the kidneys flushed with the colloid hyperosmolar solution.


Filtration characteristics of the dual-mode (Johnson and Johnson) micropore blood transfusion filter.

Stored human whole blood and red blood cells of varying age were passed through dual mode microscope blood transfusion filters. Passage through the filters resulted in markedly decreased screen filtration pressure (SFP) of the blood and increased filter weights. Numerous microaggregates were removed and SFP returned to normal. Filtration resulted in reduced platelet and white cell counts but other blood components were not adversely affected. On the basis of this research, we conclude that this micropore blood transfusion filter is effective in removing microaggregates from stored whole blood and red blood cells. It has a high capacity and rapid flow rate and is reliable during pressure transfusion.


Immunological enhancement of hybrid teratomas derived from yolk sac.

Visceral yolk sac displaced outside the uterus after fetectomy differentiates into benign teratomas. This differentiation only occurs in a syngeneic pregnancy but never in hybrid pregnancy. Hybrid teratomas, however, were obtained after the induction of active or passive immunological enhancement. These hybrid teratomas, although smaller than the syngeneic, contained tissues derived from the three germ layers.


Is very fresh blood needed in preparing leukocyte-poor red blood cells by inverted centrifugation?

It is recommended that units selected for inverted centrifugal preparation of leukocyte-poor red blood cells be less than 24 hours old. The reason for this is unclear and the recommendation poses practical problems. We evaluated the effectiveness of inverted centrifugation in reducing the WBC:RBC ratio in 31 units stored up to six days at 4 C. Leukocyte removal was at least as effective with six-day stored units as with less than one day old, averaging 77 per cent reduction with 76 per cent recovery of red blood cells. No reduction in leukocytes occurred with six days storage alone. It appears to be unnecessary to restrict leukocyte removal by inverted centrifugation to units less than 24 hours old.


Protective effect of murine sarcoma virus-superinfected mouse tumor cells against outgrowth of corresponding noninfected tumor.

Cultured lines of three newly established methylcholanthrene-induced tumors, MBK and MBL in CBA and MC57M in C57BL mice, and two mammary tumors, SBfnHC in CBA and S3W in ASW mice, were superinfected in vitro with Moloney sarcoma or leukemia virus (MSV, MLV). After superinfection, they expressed the Moloney virus-determined cell surface antigen (MCSA) and murine C-type viral p30 antigen, and produced NB-tropic C-type virus. The virus-infected tumors became more rejectable in normally susceptible syngeneic mice compared with the original noninfected line. There was no difference in 400-rad irradiated hosts. Mice that have rejected the virus-infected tumors showed an increased resistance to the corresponding noninfected tumor. The protective effect was comparable, with only one exception, to the immunizing effect of irradiated, noninfected cells. In vitro tests showed that small numbers of viable MSV-infected MBL generated cytotoxic spleen cells against both uninfected and MSV-infected MBL in syngeneic mice, while the same numbers of viable noninfected MBL did not induce cytotoxic cells. Relatively large numbers of irradiated MBL and MSV-MBL had a similar activity in inducing cytotoxic spleen cells against MBL in syngeneic hosts.


Evaluation of renal preservation using the isolated perfused rat kidney. Ischaemic damage and the effects of inosine.

An isolated perfused rat kidney has been used to determine the response to prolonged warm ischaemia and to examine renal preservation procedures. All measurements of function declined to near zero after 90 min of warm ischaemia. Measurement of total sodium reabsorption (TNa) was the most sensitive indicator of renal damage. Inosine was without effect on subsequent renal function after 60 or 90 min of warm ischaemia, or after 24 hr of cold ischaemia. Surface cooling or hypertonic citrate solution, in the cold or at 37 degrees C, significantly improved renal function, and their use in clinical renal preservation rather than that of inosine was supported by the present results.


[Changes in the mechanisms of the phagocytic activity of peritoneal macrophages during aging].

A study of the phagocytic activity in young and old rats showed that the amount of functionally active cells among macrophages of the peritoneal exudate falls with ageing. The ability of macrophages to fix, absorb and digest heterologous cells (chicken erythrocytes) decreases. This decrease of phagocytic activity is to a considerable extent due to serum factors. Probably, the age changes in the macrophages functional activity play a definite role in decreasing the efficiency of defence mechanisms during senescence.


[Effect of ouabain on an SPEV culture].

The presence of ouabain at a concentration of 4.10(-4) M in the culture medium is shown to lead to cytophysiological and morphological alterations in the cells. The synthetic and mitotic activity of the cells is reduced after 6 hrs of the experiment. The ultrastructure of all cell organelles changed simultaneously with their metabolic activity. The dynamics of ultrastructural alterations of the cells was observed. However, changes caused by ouabain did not result in death of the cell.


[Electron microscopic study of experimental allergic encephalomyelitis in dogs. I].

Disturbances typical of experimental allergic encephalomyelitis (EAE) are determined to be formed already in the initial period of sensibilization. In the spinal cord the lesions appeared relatively earlier than in the brain. Just before the neurologic manifestations of EAE a deep destruction of some myelinized axons and phagocytosis of myelin by oligodendrocytes are registered in the brain and spinal cord structures. Alterations in neurocytes and degeneration of synapses of the light type are characteristic.


[Phylogenetics of Isfahan spelt wheat--T. isphahanicum Heslot].

It is found that the genomes of T. ispahanicum are incompatible with the genome of diploid wheat species. T. ispahanicum has the AB genome structure and its genotype differs from that of other wheat species by the presence of homozygous factors P, U and S. T. ispahanicum originated from T. dicoccum or T. dicoccoides as a result of genetical recombinations and subsequent selection. Its cultivation is secondary in relation to that of emmer wheat.


Economic losses resulting from bovine cysticercosis with special reference to Botswana and Kenya.

Economic losses from cysticercosis are determined by disease prevalence, grade of animals infested, potential markets, prices of cattle and treatment costs for detained carcasses. The main features of the livestock economics of Botswana and Kenya are discussed. Botswana is more dependent on meat exports than Kenya and its cattle prices are much higher. The incidence of cysticercosis at export abattoirs in Botswana and Kenya is about 8 and 20% respectively. Annual losses in Botswana now approach 0-5 million pounds, while in Kenya they are about 1 million pounds. The loss per animal slaughtered is 2-25 pounds in Botswana and 1-50 pounds in Kenya. Some implications for veterinary research in this area are examined. Blanket treatment with a drug or vaccine would only be economical where prevalence was very high. An in vivo diagnostic test would be of use mainly with high value cattle.


[Genetic-hygienic regulation of pesticide use taking into account their potential mutagenic danger].

The principle is described of genetic-hygienic reglamentation of pesticides-mutagens application based on the estimating of the degree of their genetic hazard using several parameters characterizing the peculiarities of their mutagenic effect. Substances may be classified into groups according to their mutagenic hazard. The results are given of the evaluation of the mutagenic hazards of some pesticides and recommendations are given for the genetic-hygienic reglamentation of their application taking into account their mutagenicity.


Methods to improve the health of cattle in the tropics: conclusions and economic appraisal.

The results of the immune responses of immunised and chemoprophylactically treated calves to tick-borne (Boophilus microplus) challenge indicate that the system of immunisation was effective in protecting cattle against Anaplasma marginale, Babesia argentina (bovis), and B. bigemina. However, chemoprophylaxis was effective only against Babesia spp. but not against A. marginale. Both methods showed a substantial advantage over no control system when using native cattle breeds in a zone endemic for bovine anaplasmosis and babesiosis. Based on the net economic gain per calf starting the experiment, sizeable differences were noted at 308 days between the calves in the immunised group, chemoprophylaxis group, tick and gastrointestinal parasite control group and the experiment control group.


The influence of lorry transport on the Trypanosoma vivax infection rate in Nigerian trade cattle.

In Nigeria in 1974 and 1975 there was an apparent sharp reduction in the prevalence of trypanosomiasis of cattle at several markets and control points. Some of the decrease appears to be due to the tsetse eradication programmes and Sahelian drought, but the change to lory transport as the principal means of moving cattle from the northern grazing areas to the south-western markets, which replaced a trek of at least three weeks, was probably an important factor.


[Heritability and recurrence of growth traits of simmental crosses between Charolais and Kian breeds].

The heritability and repeatability coefficients for body weights and daily weight gains of crossbred calves at the age of 12, 15 and 18 months vary from 0.386 to 0.913 and 0.503 to 0.770, respectively. On this basis it is possible to preliminarily evaluate the animals according to their individual meat characters. This preliminary evaluation can be used with a reasonable degree of probability when finally evaluating the bulls on the basis of their progeny.


[Mutagenic activity of nitrosoalkylureas and diazoketones on corn. I].

Among the nitrozoalkylureas studied, nitrozoethylurea proved to be the most effective in respect to the frequency of induced chromosome aberrations. Diazoketones, except for bis-diazoacetyl had a negligible effect on the chromosome structure. As to the frequency of induced visible mutations (M1-M3) diazoacetone, nitrosodiethylurea, bis-diazoacetyl and nitrozodimethylurea (88.8-54.3% of mutations) were the most active among 10 studied mutagens.


Isolation of a mesogenic Newcastle diseases virus from an acute disease in Indonesian ducks.

An outbreak with mortality and acute nervous signs in ducks is reported. A haemagglutinating virus was recovered from dead and sick ducks that was neutralised by Newcastle disease antiserum. The virus was a thermostable paramyxovirus that was classified as a mesogenic Newcastle disease virus. The virus induced the infection in young ducklings following intramuscular inoculation.


Epidemiology of cattle anaplasmosis in Colombia: I. prevalence and distribution of agglutinating antibodies.

A survey to detect antibodies against Anaplasma marginale, using the Card Test, was conducted on serum samples collected from cattle of Cordoba Department and north-eastern region of the Department of Antioquia in the Republic of Colombia. The samples were from native cattle of Spanish descent (Bos taurus), Zebu (Bos indicus) and various Zebu-native crosses. The age range was between three and eight year olds. The results revealed that 90.3% of the samples were positive. All breeds showed a high prevalence of antibodies.


Toxoplasma gondii antibodies in Nigerian goats.

Toxoplasma gondii antibodies were detected in 27 of 848 sera from Nigerian breeds of goats. The significance of this finding in relation to livestock production and human public health in Nigeria is briefly discussed.


Anti-tick grasses as the basis for developing practical tropical tick control packages.

Of six grass species analysed, Melinis minutiflora (molasses grass) showed the highest anti-tick deterrent properties while Andropogon gayanus (Gamba grass) exhibited the ability to maintain a defined, constantly low, initial host tick infection property and lengthy but low to moderate field tick population. It was concluded that Melinis minutiflora is a species which would best be used in a tick control package within a marginal tick zone while Andropogon gayanus has the advantage within an endemic tick zone.


Studies on the livestock of southern Darfur, Sudan VI. Notes on equines.

Equines have been largely ignored in modern scientific literature on domestic animals, probably because they are not providers of meat and milk. Their contribution to the economy in the Sudan, however, is considerable and they are the principal means of transport both as baggage and as riding animals. They also play an important role in the supply of fuel and the distribution of domestic water in the larger villages and towns. Information on population structure is provided and descriptions, with particular reference to withers height and weight, are given of two types of donkey and of the horse. Growth curves have been derived, formulae for estimating weight from girth provided, and mean population weights, which can be expressed in terms of livestock units, have been calculated.


Surveillance of tuberculosis contacts: experience at Ealing Chest Clinic.

The results of examination of 757 contacts of 186 tuberculosis index cases seen at Ealing Chest Clinic over a period of 7 years (1968--1974 inclusive) are reviewed. The incidence of disease in non-close contacts was low and further analysis was restricted to 574 close contacts. The morbidity in this group was 9%. Asian contacts and contacts aged 15--30 years were at the greatest risk. Fourteen per cent of 151 contacts of respiratory cases positive on direct smear developed disease. The same group had the highest incidence of 'positive' tuberculin skin tests (Heaf grades 2--4). Five per cent of non-Asian contacts and 1% of Asian contacts had disease at initial examination, the excess morbidity in Asian contacts being due to disease diagnosed during follow-up.


In vitro sensitivity of Mycobacterium marinum to minocycline and doxycycline.

Using a Steers replicator technique the in vitro sensitivities of 32 clinical isolates of Mycobacterium marinum to doxycycline and minocycline were tested. Of 32 strains, sensitivity to doxycycline ranged from 3 strains (9%) with a drug concentration of 2 microgram/ml to 11 strains (34%) at a concentration of 6 microgram/ml. Sensitivity to minocycline ranged from 2 strains (6%) at the 2microgram/ml concentration to 23 strains (72%) at the 8 microgram/ml concentration. Our data suggest that a significant percentage of M. marinum strains are sensitive to therapeutically achievable levels of doxycycline and minocycline. These drugs may prove clinically useful in treating infections caused by sensitive strains of M. marinum.


Renal tuberculosis presenting with accelerated hypertension.

Hypertension is an uncommon complication of renal tuberculosis, and the association of accelerated hypertension with renal tuberculosis has not hitherto been documented in the literature; we present such a case. The diagnosis of renal tuberculosis may be difficult, particularly in the early stages of the disease, and in this case diagnosis was made by renal biopsy. The subsequent course of the patient was also particularly interesting, in that one year after starting treatment with anti-tuberculosis and anti-hypertensive medication, he developed sarcoidosis.


Tuberculosis of the liver presenting as peripheral vascular disease.

Peripheral vascular disease in African males may be associated with a tuberculous infection elsewhere in the body. The case history is described of a patient who presented with gangrenous lesions of both feet and was found to have tuberculosis of the liver. The lesions on the feet healed within 2 months of starting anti-tuberculosis chemotherapy.