Studies on metabolism of urokinase and mechanism of thrombolysis by urokinase.

Pharmacokinetics of intravenously injected 125I-labeled urokinase (125I-UK) of a molecular weight of 33,000 daltons in normal rabbits and patients with various diseases were investigated. The plasma clearance of 125I-UK in rabbits was described by a biexponential curve within six hours with a half-life of 8 minutes, 2.3 hours, respectively. The radioactivity in the liver and kidneys 15 minutes after iv injection with 125I-UK was 9.6% and 14.0% of the radioactivity injected, respectively. Approximately 80% of the total radioactive material injected was excreted in the urine in 18 hours. No increase in activator activity in the urine was observed after a large amount of UK injection. Activity uptake of 125I-UK by experimentally induced arterial thrombus was little. Lysis of the stasis thrombus was produced by injecting 7.5 x 10(-4) IU of UK in only one out of 8 rabbits. In vitro contact experiment revealed that transfer of 125I-UK to plasma clot is slow (24 hours for 10% of 125I-UK by plasma clot). In 4 patients plasma clearance of 125I-UK was essentially similar to that in rabbits. From the results obtained optimal dosage regimen of UK administration for complete thrombolysis in vivo was discussed.


Plasminogen activator (urokinase) from cultured cells.

Secretion of large quantities of urokinase by cultured renal cells suggested tissue culture as a means of production to meet demand for the material and to obtain guidelines for optimization of production. Rates of secretion and overall yields of urokinase from confluent cultures of renal cells have been studied in relation to species differences, effects of passage of cells, inoculum density, and volume of maintenance media. Added in part by an advantage gained through addition of glycine to maintenance media, it is now possible to harvest urokinase at concentrations of the order of 800 CTA units per ml. Such concentrations are of the order of 10(2) times that occurring in human male urine.


Influence of coagulation on the activation of plasminogen by streptokinase and urokinase.

Human plasma was mixed with Ca++ or thrombin, and urokinase (UK) or streptokinase (SK) and a chromogenic substrate (S-2251: H-D-Val-Leu-Lys-pNA) specific to plasmin. The hydrolysis of S-2251 was higher when clot was formed by the addition of Ca++ or thrombin than in the absence of clot. The hydrolysis of S-2251 by euglobulin in the presence of UK was also higher when clot was formed, thus, inhibitors may not be related to the better activation of plasminogen, in the presence of fibrin clot. It may be suggested that plasminogen was better activated by activators (UK and SK) in the clot than in its absence.


Purification of urokinase by a beta-naphthamidine affinity column.

Urokinase was purified by affinity chromatography using 6-amino-naththamidine-(2), a new specific ligand based on the urokinase inhibitor beta-naphthamidine. Urokinase was firmly bound at pH 7.0 and could be eluted at pH 3.0. The protein which passed the column at pH 7.0 without being bound did not contain any urokinase activity. This is an important property because it can be utilized for raising a monospecific urokinase antiserum by absorbing unspecific antibodies with only a minor loss of antiserum titre.


Fibrinolysis in the pigeon (Columba livia).

The presence of plasminogen activator in the euglobulin fraction of pigeon plasma, was demonstrated by conspicuous lysis on unheated fibrin plates; human as well as bovine fibrin were susceptible to lysis. The presence of free plasmin in euglobulin fraction was indicated by lysis on heated fibrin plates.


Comparative studies of blood coagulation in hibernating and non-hibernating frogs (Rana tigrina).

1. During hibernation in frogs (Rana tigrina) there occurs prolongation of several clotting tests, viz, whole blood clotting time, plasma recalcification time, cephalin time and prothrombin time. 2. The ambient body temperature of the frog during winter hibernation is low and the retarded blood clotting at lower temperature may play an important protective role against intravascular thrombosis. 3. Shorter plasma recalcification time in low-spun plasma as compared to high-spun plasma indicated the presence of procoagulant activity in platelets/leucocytes of frogs.


Detection of an abnormal plasma clot structure by a simple rigidity assay.

We report here on a patient whose abnormal fibrin clot was detected via the measurement of clot rigidity with a simple buoyant inner cylinder elastometer. The patient's clinical coagulation studies were all within normal limits except for prolonged thrombin and reptilase clotting times and high level of fibrin split products. The measured rigidity of the patient's clot was approximately ten times lower than that of a clot formed from normal pooled plasma. Light scattering studies indicated that this modified structure was not caused by a gross change in gel fiber morphology. Antithrombin activity was eliminated as a possible cause of the altered clot structure; this suggests the possibility of a modified fibrinogen. Abnormalities in the reptilase time and fibrinogen levels in two siblings support the hypothesis that the modification is an inherited defect. We suggest that the simple measurement of rigidity can be used rountinely to detect abnormalities in plasma clot structure. The screening for such disorders should be of importance to clinician, patient, and biochemical researcher.


An acquired abnormal fibrinogen associated with thromboembolic disease and pseudotumor cerebri.

An abnormal fibrinogen was found in a patient associated with disabling recurrent phlebitis and pulmonary emboli, pseudotumor cerebri, gout and endometriosis. The fibrinogen is characterized by (1) abnormal side-to-side and end-to-end polymerization, (2) abnormal fibrinopeptide release, (3) a delayed gamma-gamma dimerization of the non cross-linked fibrin, (4) a pH optimum of 7--7.8, and (5) a deviation from normal amino acid composition with regard to lysine, aspartic acid, glutamic acid and serine. Since no defect has been found in any of her three children, and since the prothromin and partial thromboplastin times vary from time to time, it is assumed that the defect is acquired. Liver disease, usually associated with acquired abnormal fibrinogen, has been excluded as an etiological cause since liver function tests and biopsy are completely normal.


[Determination of theophylline blood level by high-pressure liquid chromatography (author's transl)].

The authors describe an easy, rapid, selective and reproducible quantitative determination of theophylline using a high-pressure liquid chromatograph. Plasma theophylline determination is very useful to establish an efficaceous and non toxic posology for each patient.


[Dismutation as a metabolic pathway : transformation of the trimethyl 3,5,5, cyclohexanone (author's transl)].

Besides novel routes of biotransformation of xenobiotic substances recently reported, such as N-glucuronidation of teritary amines and quaternary ammonium componds, N-glucosylation, N-carbamylglucuronide formation from a primary amine, C-glucuronidation, conjugation with long-chain fatty acids, with polypeptides, carbon-chain elongation, stereospecific inversion of configuration at a satured carbon atom, formation of methylthio metabolites, the authors have described a new metabolic pathway: dismutation, in the case of 3,5,5, - trimethylcyclohexanone (dihydroisophorone). As a matter of fact, this compound leads, in vivo, to the formation of isophorone alpha and of cis and trans 3,5,5, - trimethyl cyclohexanols. These compounds, extracted from the urine of treated rats and rabbits, have been identified by gas-liquid chromatography and thin-layer chromatography.


[Acute toxicity of orthochloroparanitroanisole (OCNA) and orthochloroparaanisidine (OCPA) (author's transl)].

The acute effects of two industrial substances were studied in mice, rats, rabbits and guinea pigs: - lethal concentration 50 (L.D. 50) in mice and rats after intraperitoneal and oral administration; - investigation of cell growth inhibition (Hela cells), I.D.50 = inhibitory dose 50%; - neuropharmacological effects Histopathological investigations and biochemical analysis pointed out hepatic and renal damages; besides hematological disturbances were found. Both products had mild irritant effects on rabbits skin and eyes. They produced skin sensitization in guinea pigs.


[Effect of levomepromazine on atrioventricular conduction tissue (author's transl)].

The effect of levomepromazine on sinusal automaticity, myocardial excitability and auriculoventricular conduction have been studied in dogs by measuring the spontaneous heart rate, the effective refractory period of the conduction system, the time of auriculonodal and infrahisian conduction. Chloralose-anaesthetized dogs were administered 5 mg/kg levomepromazine via IV route and 10 mg/kg one hour later. While sinusal automaticity is never altered, the other parameters studied were modified only when high doses were used. Therefore these quinidine-like effects are very unlikely to come up even following suicidal massive ingestion of levomepromazine.


The influence of orphenadrine HCl in overdose alone and in combination with droperidol on respiration and circulation in the rat.

Orphenadrine HCL was intravenously administered to rats under urethane anesthesia to investigate whether the primary cause of death in orphenadrine intoxication is respiratory arrest or cardiac standstill. The spontaneously breathing animals died from apnoe after a mean dose of 63 + 11 mg/kg. The artificially ventilated animals died from cardiac arrest after a mean dose of 144 +/- 47 mg/kg. It was concluded that primary cause of death is respiratory insufficiency and that hypoventilation can mask the cardiotoxicity of orphenadrine. On the analogy of earlier experiments in dogs the ability of droperidol to counteract the influence of orphenadrine was investigated. Droperidol enhanced the influence of orphenadrine on respiration and had no influence on the cardiotoxic influence of orphenadrine in the rat.


Induction of cataracts in the rat by derivatives of (4' -pyridyl) - 1 piperazine.

A structure ocular toxicity study in the rat of (4' - pyridyl) - 1 piperazine and of some derivatives with psychopharmacological profile, allows some interesting conclusions. (4' - pyridyl) - 1 piperazine does not lead to crystalline lens opacity, though some aryloxypropanol or aryloxypropyl derivatives do. At least, (2' - pyridyl) - 1 piperazine and one aryloxpropanol derivative do not improve cataract. So the appearance of cataracts is probably due to substitution of an alkylaryl side chain on the N-4 position of (4' - pyridyl) - piperazine.


[Results after split-course irradiation of bronchial carcinoma (2 series) (author's transl)].

This report concerns 1092 patients with bronchial carcinoma, exclusively irradiated by means of the split-course method. Only squamous cell carcinomas have a chance to survive the 5-year limit: all stages in 9/328 = 2.7%, T1 and T2 in 5/48 = 10%. The dependence of the effect on the radiation dose can be confirmed for squamous cell carcinoma but not for anaplastic tumors. Doses higher than 4500 rad do not bring about a longer survival for the latter. Advantages of the split-course method are: The treatment is better tolerated, operability of questionably operable cases can be checked once again after the first irradiation, series, the dose may be determined from the therapy effect in every individual case.


[Irradiation prophylaxis of keloids and cicatricial hypertrophies (author's transl)].

The results obtained for 100 patients by combined surgical and radiation therapy are presented and by means of exemplary cases illustrated. As sson as 24 to 48 hours after excision of the keloid by mostly atraumatic surgical technique, and closing the wound as tension-free as possible, radiation therapy is begun. This takes place under the conditions of surface therapy in single doses of 1.5 Gray two or three times per week up to a total dose of 9 to 12 Gray. Good cosmetic and functional results can be achieved with this technique. The rate of recurrences is extremely low. The radiation load to the patient is so small that it seems justifiable to recommend the combined treatment as the routine method for therapy of keloids. In cases of a known disposition for developing keloids or cicatricial hypertrophies, postoperative radiation therapy is indicated as a prophylactic measure, especially after surgery in the facial region.


[Possibilities of variation in skip pendulum irradiation (author's transl)].

Irradiation techniques should be judged not by dose distribution only but also by the effort necessary for their realization. Skip pendulum irradiation is a technique excelling not only through suitable dose distribution but through effortless adjustment as well. The possibilities of variation in skip pendulum irradiation are examined, a schedule facilitates the choice of field breadth and pendulum angle. Skip pendulum irradiation should gain importance, too, for the bremsstrahlung from a linear accelerator.


[Are the actual criteria of tumor classification and therapy valuation sufficient for the tumor therapy? (author's transl)].

The classical notions of tumor diagnosis (classification and diagnostic accuracy) as well as the generally accepted criteria for evaluating the success of the tumor therapy (mortality graphs, survival time and remission) are submitted to a critical examination. It is found that the actual version of these notions and criteria can cause serious errors in diagnosis and valuation. It seems therefore indispensable to complete and correct these generally used notions. However important scientifically founded and precisely defined parameters for tumor therapy and its valuation may be, one must never forget on the other hand that the treatment of a tumor patient is an individual problem and that  the most important task of the oncologist remains to give psychological guidance to every single patient.


The significance of leucocytosis in the X-irradiated tumour-bed.

(1) Present experiments confirm previous studies (Beck and Engel[1], 1927) according to which a tumour implanted s.c. into an X-irradiated area of mice is inhibited in its growth by 50 to 66% as compared with the implant of the nonirradiated side of the same animal. In the present series the growth inhibition amounted to practically 50%. (2) Exposure of the mouse skin to X-radiation caused a marked hyperleucocytosis within the first 24 hours, with a rapid decrease to normal levels within 4 or 5 days. (3) The inhibitory effect of X-radiation on the tumour growth and the inflammatory response of the skin (leucocyte count) did not run a parallel course except during the first few days after irradiation. The conclusion is drawn that hyperleucocytosis of the tumour bed is not the only cause for the tumour growth inhibition.


[Behaviour of the peripheric leucocyte count and leucocyte resistance in rat after acute whole-body irradiation with 60Co-gamma-rays (author's transl)].

Wistar-rats were exposed to whole-body 60Co gamma irradiation and underwent continuous blood analysis through 70 days. By means of these experiments information as to the reliability of "values of the leucocyte resistance against ultrasound (LRW)" should be obtained in order to diagnose radiation injury. For all the dose ranges studied (from 10 R to 500 R) it was possible to ascertain a qualitatively radiation-specific LRW-curve being independent of the behaviour of peripheric leucocyte counts.


Differential radiosensitivity of two mammalian cell lines after hyperthermic pretreatment.

Hyperthermia in combination with 60Co-gamma-therapy not only increases the radiosensitivity of mammalian cells, it also can create a greater selectivity between individual cell populations. Tw established Chinese hamster cell lines (V79 and B14F28) showed a similar radiosensitivity at 37 degrees C, but exhibited a marked difference in their response to 60Co-gamma-rays when they were pretreated with mild hyperthermia (1 hour at 42 degrees C): About 50% of each cell type survived a dose of 400 rad 60Co-gamma-rays alone, while the same dose delivered in combination with hyperthermia was survived by 40% of the B14F28 cells and by only 2.4% of the V79 cells. Heat alone also caused cell death and cell cycle changes (as measured by flow-microfluorometry) to a different extent: 4 hours at 42 degrees C decreased survival of V79 cells to 1.3% while 70% of the B14F28 cells formed colonies. This differential response to hyperthermic killing and thermal radiosensitization is similar to the different RBE-values for survival of both cell lines after high LET pion irradiation.


Initial events in radiation-induced atheromatosis. III. Effect on lipase activity.

Treatment of large blood vessels with ionizing irradiation leads to the development of atheromatosis when the serum lipid levels are sufficiently high. In order to answer the question whether a disturbed lipid clearance in the arterial wall plays a role in the accumulation of the lipids it was of interest to examine the effect of X-irradiation on the lipase activity. Triglycerol lipase was tested in a homogenate from rabbit carotid arteries, glycerol-tri-oelate was used as a substrate and the hydrolysis assayed at pH 6.4 at 37 degrees C. Under the conditions used, an hydrolytic activity could be measured of 7.5 nmoles . mg prot-1 . hr-1. The lipase activity was also tested in the carotid arteries obtained from rabbits which had been locally irradiated with 20 Gy of X-rays. No clear radiation effect on the lipase activity was found 4, 8, 20, 24 and 72 hours after irradiation. The accumulation of lipids is thought to be caused by a higher influx of lipids from the serum as a result of endothelial damage by X-irradiation rather than a defect in the clearance capacity of the arterial wall.


Effect of STA-MCA anastomosis on the course of experimental acute MCA embolic occlusion.

The experiments in this report were designed to evaluate the effect of superficial temporal-middle cerebral artery (STA-MCA) anastomosis on the course of middle cerebral artery (MCA) occlusion by emboli while avoiding a vessel clipping technique as well as the use of long-acting barbiturate anesthesia. Dogs were divided into 3 general groups: A) embolus placement 1 h following anastomosis; B) embolus placement 5 h prior to anastomosis; C) control group without anastomosis. Anastomosis prior to MCA occlusion has a favorable clinical effect and reduces the size of an infarction. Anastomosis 5 h after embolus placement is deleterious unless other therapeutic modalities can be shown to delay the course of infarction.


Results of electroencephalographic monitoring during 367 carotid endarterectomies. Use of a dedicated minicomputer.

Three hundred sixty-seven carotid endarterectomies were monitored using routine electroencephalographic (EEG) techniques. In 9.8%, changes in the EEG followed clamping of the internal carotid artery and could roughly be grouped into 6 patterns. The most common (47%) was rapid unilateral or bilateral attenuation of background anesthetic-induced fast EEG activity. Conclusions drawn from studies of the 9 patients who had immediate postoperative neurological deficits of varying degrees are presented as they illustrate monitoring techniques that are useful for early recognition of cerebral ischemia. Thirty-five patients were monitored with both routine and computerized techniques--the latter proved more useful than the former on all counts.


Autopsy study of cerebrovascular disease in Japanese men who lived in Hiroshima, Japan, and Honolulu, Hawaii.

Evidence of cerebrovascular disease at autopsy was compared in 2 groups of men: 186 long-time residents of Hiroshima, Japan, and 253 men of Japanese ancestry long resident in Honolulu, Hawaii. They were 45 to 71 years-of-age at death. Atherosclerosis of the circle of Willis and its major branches, sclerosis of the intraparenchymal arteries and the frequency of cerebral hemorrhage and cerebral infarct were compared in the 2 populations. The Honolulu subjects had significantly more atherosclerosis of the circle of Willis, but less intraparenchymal artery sclerosis and less cerebral infarction. Cerebral hemorrhage was equally frequent in the 2 cities. It was concluded that cerebral infarction is more frequent in Japanese men in Hiroshima than Honolulu, and that men of Japanese ancestry in Honolulu are spared an appreciable risk of cerebral infarction through decreased frequency of intraparenchymal arterial sclerosis despite higher levels of atherosclerosis of large intracranial arteries.


Cerebral artery thrombosis and intramural hemorrhage.

Thirty-nine thrombosed arterial segments of the branches of the circle of Willis were studied by a complete serial section technique. Twenty-two patients had been hypertensive and 8 had hypercholesterolemia before the onset of cerebral artery thrombosis. The histological characteristics of the thrombosed arterial segments were intramural hemorrhage in 28 segments, superficial edema of the fibrous cap of the atheroma of fibrous plaque in 4, rupture of the atheromatous plaque in 1, superficial accumulation of foam cells in the atheroma in 1 and an atheroma or fibrous plaque without any other changes in 5. They were many intramural small blood vessels in the atheroma or fibrous plaques of 22 segments with intramural hemorrhage. Fibrinoid degeneration of these small blood vessels was noted in 5. These findings suggested that intramural hemorrhage from the intramural small blood vessels was the major cause of cerebral artery thrombosis and that persistent hypertension not only promoted cerebral atherosclerosis but also induced hemorrhage from the intramural small blood vessels.


A new canine model of proximal internal carotid embolism.

A new model of internal carotid artery embolism was developed using autologous clot. The clot was prepared by incubating blood at room temperature for 2 hours to inactivate plasminogen activators and then refrigerating it at 4 degrees C for 22 hours. The purpose of the experiment was to devise a model of the intravascular lesion and not of stroke itself. The dog was chosen as the experimental animal since it has a maxillocarotid artery which permits collateral flow beyond proximal internal carotid artery occlusions. A volume of clot measuring 0.25 to 0.30 cc was sufficient to occlude the artery for 48 hours in 80% of the animals without causing major strokes. We have used this model to study clot radiolabeling and suggest it may also have application for evaluating thrombolytic drugs.


A simplified method for measuring regional blood flow.

A method of measuring regional blood flow (RBF) that is simple in procedure and calculations is described. By arresting flow promptly after a short pulse of diffusible tracer, it is feasible to equate the tracer retained in the tissue (Cfi) with that delivered by the blood. If the arterial pulse is characterized by its mean concentration (Ca) over a known duration (delta t), RBF can be estimated from Cif/Ca delta t). The error involved is relatively small and can be corrected for. If the amount of tracer injected is known, this procedure also provides an estimate of cardiac output and its fractional distribution to the regions sampled. The values obtained for RBF in 4 regions of brain were similar to those previously reported.


Cerebral blood flow immediately following brief circulatory stasis.

Cerebral blood flow was studied in rabbits immediately following complete circulatory stasis of varying duration. Systemic arterial pressure was measured continuously. The postischemic circulation was examined both by an infusion of carbon black and, in separate experiments, by injection of 14C-antipyrine into the blood. We examined the relationship between the duration of stasis, the postischemic arterial pressure, and the amount of cerebral reperfusion. As stasis increased from 5 to 30 min the pressure required to achieve reperfusion of the entire brain rose from 20 to 100 torr. Following even temporary exposure to arterial pressures above 110 torr all areas of the brain were generally reperfused. Blood flow in reperfused brain varied directly with arterial pressure, indicating failure of autoregulation. At normal (preischemic) arterial pressure, postischemic cortical flow was twice the normal rate. The data indicate that the pressure required to initiate flow in ischemic brain increases as the duration of stasis is lengthened and that once flow occurs there will be a significant hyperperfusion unless systemic arterial pressure is lowered to the low normal or hypotensive range.


Critical appraisal of cerebral blood flow measured from brain stem and cerebellar regions after 133 Xe inhalation in humans.

Validity of regional blood flow (rCBF) measurements recorded over the human posterior fossa after 133Xe inhalation was tested. Recording of counts from both brain stem and cerebellum (BSC) was reproducible and contamination by counts derived from surrounding anatomical structures was low and no greater than that found over hemispheres. BSC values were F1 = 99 +/- 19 ml/100g brain/min, F2 = 17 +/- 4 in reasonable agreement with data reported from experimental animals. BSC flow values showed significant correlation with the state of awareness as judged by clinical and EEG evaluation with lowest F1 values in semicoma and step increases in stupor, non-REM sleep, drowsiness, rest, activation, REM sleep and highest values during focal and generalized epileptic seizures.


Treatment of acute focal ischemia with continuous CSF drainage and mannitol.

A simple implanted device was used to occlude acutely the left middle cerebral artery (MCA) of 32 conscious cats. Groups of 18 cats each were treated with continuous cerebrospinal fluid (CSF) drainage, mannitol (1 gm/kg i.v.), or a combination of continuous CSF drainage and mannitol (1 gm/kg i.v.). Eight cats served as a control group. The neurological status of cats treated with mannitol improved transiently. Perfusion with a mixture of colloidal carbon and buffered paraformaldehyde was carried out 12 hours following MCA occlusion. Gross swelling of cerebral tissue, distribution of colloidal carbon, and breakdown of the blood-brain barrier to fluorescein were similar in the 4 groups. Reduction of mean capillary luminal diameter to 4.5 +/- 1.0 micron (control 6.5 +/- 1.0 micron) in the left Sylvian cortex was unaltered by treatment. A significant difference in the distribution of severe neuronal alterations was not demonstrated.


Circulating platelet aggregates in sickle cell disease patients with and without vaso-occlusion.

In vivo circulating platelet aggregates (CPA) were evaluated in 18 patients aged 6 to 17 years with sickle cell disease and in 11 age and sex matched normal subjects. Twelve patients with sickle cell disease were in steady state and 6 had vaso-occlusive crises. CPA in patients in steady state were similar to those in normal subjects (mean 6 +/- 1% compared to 5 +/- 2%, respectively), whereas patients with vaso-occlusive crisis in acute state had significantly higher CPA (mean 39 +/- 8%) than patients in steady state or normal control individuals (both p less than 0.001). CPA decreased in patients with vaso-occlusive crisis (mean 11 +/- 4%) on the tenth day, in association with clinical improvement. This study suggests that in vivo platelet aggregate formation activity, although normal in sickle cell disease patients in steady state, is significantly increased in patients with vaso-occlusive crises.


External carotid artery in internal carotid artery occlusion. Angiographic, therapeutic, and prognostic considerations.

Twenty-three instances of internal carotid artery occlusion occurring with minimal neurological deficit in 22 patients are described. Although each of these patients was referred to the neurosurgical service for evaluation for an extracranial-intracranial microvascular bypass procedure, complete arteriographic evaluations of their cerebrovasculature suggested that alternative methods should be the treatment of choice. For each patient reported the ipsilateral external carotid artery was demonstrated by angiography to be an important source of collateral blood supply to the cerebral hemispheres or retinae distal to the occluded internal carotid arteries. Ten patients with no significant atherosclerotic narrowing or ulceration of the external carotid artery have remained free of symptoms of cerebral ischemia for 6 to 40 months. In twelve patients who developed delayed recurrent cerebral or retinal ischemia ipsilateral to their internal carotid artery occlusion, there were found obstructive and/or ulcerative plaques involving the common and/or external carotid arteries. Thromboendarterectomy in 11 of these patients gave complete relief of ischemic symptoms during the 4 to 36 months of postoperative follow up. One of these 12 patients refused operation and went on to develop a major cerebral infarction. Angiographic identification of a functionally important external carotid artery ipsilateral to an internal carotid artery occlusion carries considerable prognostic and therapeutic significance.


Tranexamic acid in subarachnoid hemorrhage. A double-blind study.

The effects of intravenous tranexamic acid were compared with placebo in 64 patients with subarachnoid hemorrhage. A double-blind procedure was used. One gram of tranexamic acid was given intravenously every 4 hours up to the time of operation on an intracranial arterial aneurysm or for up to 21 days after the first bleeding if operative treatment was not feasible. There were no differences in re-bleeds, morbidity or mortality between the tranexamic and placebo-treated groups. No thromboembolic complications were noted in either group. Our results do not support the use of tranexamic acid in subarachnoid hemorrhage in daily doses of 6 g.


Prognosis in patients with infarction and TIA in carotid territory during and after anticoagulant therapy.

One hundred seventeen patients, 31 with TIA and 86 with cerebral infarction, had angiographically verified atherosclerosis within the relevant carotid artery territory and normal CSF. They were treated with anticoagulants for a mean of 11.1 months. No TIA but 1 cerebral infarction, appearing during inadequate anticoagulant therapy, was registered. Seventy-six of the patients, 20 with TIA and 56 with infarction, were followed for a mean of 4.4 months after cessation of anticoagulants or during inadequate antinecessitating re-institution of anticoagulant therapy. Long-term, anticoagulant treatment can be recommended in carefully selected patients with TIA, and also with infarction in the carotid territory.


Omental transposition to brain of stroke patients.

The intact omentum was transposed to the surface of the brain in three aphasic patients who had stabilized following a dominant hemisphere ischemic stroke. The procedure was found to be safe, causing little physical disfigurement. Subjective and objective improvement in these patients, who are on a strict experimental protocol, has provided encouragement to continue this study in a deliberate and critical manner.


Frequency of focal cerebral transient ischemic attacks during a 12 month period. The Copenhagen city heart study.

As an offshoot of a larger prospective cardiovascular population study, the present study aimed to determine the 12 months frequency of focal cerebral transient ischemic attacks (TIAs) in persons randomly selected after age stratification from the Copenhagen city population register. A questionnaire of 5 questions pertaining to cerebrovascular attacks sustained within the last 12 months was distributed to 2,357 persons. The TIA-questionnaire was returned by 88%, of whom 22% responded affirmatively to one or more questions. The positive responders were interviewed by phone, and when suspected of having TIAs they were examined by a neurologist. A total of 11 persons proved to have had TIAs, which for the age group of 60 years and over gives o 12 months frequency of 8/1000. Dizziness, ophthalmologic problems and migraine were the most frequent causes of a "false" positive response.


Brain stem dysfunction in transient global amnesia.

A patient with transient global amnesia also had transient bilateral gaze nystagmus which was detected both by conventional bedside examination and upon electronystagmographic recording. The nystagmus was absent one week later indicating recovery of the temporary brain stem deficit. The recording of objective evidence of brain stem dysfunction in the form of gaze nystagmus in a patient who had transient global amnesia, suggests that both were due to a transient ischemic attack involving the cerebral blood supply in the vertebrobasilar distribution.


Effect of intravenous ethanol on cerebral vasospasm produced by subarachnoid blood.

The cat basilar artery was exposed using the transclival approach. After administration of 5% ethanol via intravenous infusion, vasospasm was produced by applying the animal's fresh arterial blood to the exposed artery. The resultant vasospasm was of markedly reduced intensity and duration as compared to vasospasm in control animals. In ethanol-treated animals with spasm induced from non-autogenous fresh arterial bloof free of ethanol, a reduction in the duration of vasospasm was noted although the initial intensity of spasm was similar to control animals. There was no anti-spasm effect if the ethanol infusion followed the production of vasospasm.


Brain edema during ischemia and after restoration of blood flow. Measurement of water, sodium, potassium content and plasma protein permeability.

The left cerebral hemisphere of Mongolian gerbils was used to elucidate the mechanisms of brain edema which develop during cerebral ischemia and after restoration of cerebral blood flow following temporary ischemia. Water content was measured by the tissue-drying method. Sodium and potssium ion concentration was measured by flame photometry. Passage of 131I-albumin (RISA) from blood to the cerebral parenchyma was measured on a gamma scintillation counter. Our findings indicate that pure cytotoxic edema develops during ischemia and during a short period after restoration of cerebral blood flow. Vasogenic edema, which is accelerated by the leakage of plasma constitutents from blood due to blood-brain barrier damage, developed after restoration of the cerebral blood flow. After less than 1 hr of ischemia, restoration of the cerebral blood flow drastically reduced the degree of brain edema. However, restoration of the cerebral blood flow greatly worsened the brain edema following more than 3 hr of ischemia.


Small animal model for investigation of subarachnoid hemorrhage and cerebral vasospasm.

A method for induction of subarachnoid hemorrhage (SAH) in a rat model is described. Resolution of the hemorrhage was documented photographically and microscopically at intervals from 1 hr to 8 days. Photographs indicated that most of the hemorrhage was resorbed within 3 days, an observation confirmed microscopically by the amount of red blood cells in the subarachnoid space. Significant cerebral vasospasm was documented within the first 2 days after the induction of hemorrhage with the basilar artery returning to baseline values at an average of 3 days followed by moderate dilatation at 5 to 8 days. The suitability of the rat as an animal model for further investigation of subarachnoid hemorrhage is discussed.


Serum cardiac enzymes in stroke.

Serum cardiac enzyme levels (CK, LDH, SGOT) were estimated and the ECG recorded for 4 days following admission of 288 patients (Group I) to a stroke intensive care unit. Sixty-four of these patients, subsequently found not to have strokes, served as controls. Mean serum levels of all 3 cardiac enzymes were elevated in 8% of the 224 patients with stroke. The mean serum enzyme levels in patients with transient ischemic attacks (TIA) did not differ from controls. In a second group of 230 patients with stroke (Group II) serum CK levels were measured and the isoenzyems were fractionated to determine the tissue source of the enzymes. One hundred and one patients had raised total CK values and 25 of these (11%) had raised CK-MB (heart) iso-enzyme, the remainder having CK-MM (skeletal muscle) fraction. No serum CK-BB (brain) iso-enzyme was detected in any patient. Patients with positive serum levels of CK-MB has more evidence of acute myocardial ischemia on ECG (p less than 0.05), and more cardiac arrhythmias (p less than 0.001) than those with normal CK levels. Scattered areas of myocytolysis were found in the myocardium at autopsy in one patient. The acute rise in serum cardiac enzymes which we have recorded in the initial stages of stroke suggest that acute myocardial involvement is a commoner complication than is generally recognized. Also, since the CK-MB rises were modest and progressive, it is more likely that this acute myocardial dysfunction is a consequence, rather than a cause, of the acute cerebrovascular lesion.


Chronic subdural hematoma presenting as transient neurologic deficits.

Four patients with symptoms of transient neurological dysfunction were subsequently found to have chronic subdural hematomas (CSDH). The frequency of these episodes diminished significantly after evacuation of the hematoma. The effects of vascular compromise due to the CSDH and to cardiovascular events, more commonly implicated in transient ischemic attacks (TIAs) may be additive. The inclusion of a computerized axial tomographic (CAT) scan in the evaluation of some patients with presumed TIAs is recommended.


Brain metabolism following bilateral carotid occlusion in 2 different models of experimental hypertensive rats.

Brain metabolites and arterial acid-base measurements were made one hr after bilateral carotid artery occlusion in 2 different models of hypertensive rats. Animals used included renovascular hypertensive rats (RHR) with an altered renin-angiotensin system and desoxycorticosterone hypertensive rats (DHR) with low plasma renin activity (PRA). The mean value for supratentorial lactate of 7.41 mM/kg in RHR was significantly higher than in DHR (3.90 MM/kg) or in control normotensive rats (3.10 - 2.56 mM/kg). Concomitantly, the lactate/pyruvate ratio tended to increase and ATP to decrease in RHR only. In these same rats (RHR) infratentorial lactate was also increased. The results suggest that bilateral carotid occlusion leads to anaerobic metabolism of the brain in RHR but not in DHR, suggesting that the renin-angiotensin system may play some role in the susceptibility to cerebral ischemia following carotid occlusion in the hypertensive rats.


Cerebral vasomotor reactivity in normotensive and spontaneously hypertensive rats.

Intravenously injected metaraminol induced a larger blood pressure increase in spontaneously hypertensive rats (SHR) than in normotensive controls (NR) when the pressure was raised from the same starting level. Cerebral blood flow (CBF) response in NR was either perfect autoregulation, partial autoregulation or "break-through." When present, the autoregulatory response was very rapid, i.e. the flow returned to the initial value within 10-15 sec. All SHR showed an initial prompt vasoconstrictor response which was followed after 30-40 sec by a gradual flow increase. The blood pressure elevation was highest in SHR when hypertension was induced by compression of the aorta, which supports the hypothesis that the enhanced response is, at least in part, a consequence of an increased vessel wall to lumen ratio. The characteristic CBF pattern observed in SHR after a metaraminol-induced rise in blood pressure was not seen when the blood pressure was increased by aortic compression, which suggests an effect of the drug separate from its pressor effect. During maximum vasodilatation the cerebrovascular resistance (CVR) was considerably higher in SHR than in NR. Assuming an equivalent vessel density in the 2 groups, our results suggest that structural changes in resistance vessels in SHR encroach on the lumen.


Platelet coagulant activities in arterial occlusive disease of the eye.

Ischemic optic neuropathy and retinal arterial occlusion are 2 forms of arterial occlusive disease affecting the eye. Reports in the literature suggest platelet hyperactivity in acute arterial occlusive diseases affecting other organ systems. Therefore, 14 patients with ischemic optic neuropathy and 17 patients with central or branch retinal artery occlusion were studied to determine whether platelets have a role in the pathogenesis of these vascular occlusive disorders. The results of the following investigations were no different in these patients compared with those in 18 control patients with non-vascular eye diseases: prothrombin times, partial thromboplastin times, plasma fibrinogen, factor V, factor VIII, platelet counts and threshold concentrations of ADP, epinephrine and collagen resulting in secondary platelet aggregation and serotonin release. In contrast, platelet coagulant activities concerned with the early stages of intrinsic coagulation were significantly increased in patients with retinal artery occlusion without hypertension or type IV hyperlipoproteinemia, but generally normal in patients with ischemic optic neuropathy and in patients with retinal artery occlusion associated with hypertension, type IV hyperlipoproteinemia, diabetes mellitus and generalized atherosclerosis. These results are consistent with a platelet contribution to retinal arterial occlusive disease in patients without other known contributing factors such as hypertension, serum lipid abnormalities, diabetes mellitus and generalized atherosclerosis and may have implications regarding prophylaxis.


Cerebral arteritis in scleroderma.

Central nervous system (CNS) involvement is rare in scleroderma unless there are concomitant abnormalities in renal or lung function or malignant hypertension. A 43-year-old woman with typical scleroderma developed subacute encephalopathy despite absence of the above abnormalities. Cerebral angiography demonstrated a focal arteritis. The patient improved while being given corticosteroids. We believe this case indicates that cerebral arteritis can occur in scleroderma.


Fusiform basilar aneurysm simulating carotid transient ischemic attacks.

Fusiform aneurysms of the basilar artery are extremely unusual. Most show signs of a posterior fossa mass. One case is reported which presented with recurrent transient ischemic attacks suggesting carotid vascular disease. Failure of an appropriate endarterectomy to relieve the symptoms, and later brain stem infarction, led to the correct diagnosis. Whenever recurrent or new symptoms appear following carotid vascular surgery, other diagnoses must be considered.


An overview of a hierarchy of planning models for Regional Blood Bank Management.

Optimal regionalization of a blood banking system requires a hierarchical structure based on an analysis of preexisting elements in the region to determine at what level of activity economics of scale, cost effectiveness and efficiency will be greatest. We have applied operations research techniques to segments of the blood service complex. This paper is an overview of the general results of this research. From analysis of the data in each segment, a mathematical response function is developed for such managerial processes as demand forecasting, requirements computation, crossmatch and recycle control at each level of the hierarchy in a regional system. These processes in independent hospital blood banks are contrasted with those in hospital blood banks and transfusion services which are dependent on central blood banks for their supply. An example is presented of a model which is useful in the planning of a regional system. Implementation of these hierarchical models in hospital blood banks can reduce outdating, size of inventories and shortage. In central blood banks, these models can minimize shipment quantities, determine optimal transshipments and the most efficient routing.


Effects of prolonged room temperature holding of whole blood intended for preparation of components.

Current FDA regulations require that platelet concentrates must be prepared within four hours of whole blood collection. To determine if this time period was critical for the harvesting of viable platelets and other blood components, whole blood was held at room temperature for four, six or eight hours after which various components were prepared. Our results indicate that up to eight hours storage had no detrimental effect on platelet yield, recovery in vivo or lifespan. AHF activity, supernatant hemoglobin and red blood cell ATP were also unaffected.


Granulocyte progenitor cells (CFU-C) in peripheral blood of normal volunteers following cell collection by continuous flow centrifugation.

During leukapheresis, the donor undergoes cellular depletion which must be compensated. Moreover, the cellular suspensions obtained contain a certain proportion of granulocyte progenitors that form colonies in agar (CFU-C). These findings prompted us to investigate the effect of a donation by cytapheresis on the number of circulating CFU-C present in the donor. Our investigations were carried out on the day the donation was made, and at further fixed dates for a period of six months. Our study covers 25 cases, corticoid premedication was only given to granulocyte donors and not to platelet donors. In the majority of cases, there were no postdonation effects. A few donors had a less stable circulating CFU-C count than is generally considered normal for a healthy subject. In some, quite wide variations were observed but immature cells never appeared in the circulating blood.


The priming of extracorporeal circuits: the effect on canine blood elements.

Improving hemocompatibility is of major interest in extracorporeal circulation (ECC). Changes in numbers and functions of the blood cells during ECC have been ascribed to the nonphysiologic materials of the circuit. In this study, commonly used priming fluids (banked blood, Ringer's lactated solution, gelatin solution and dextran 70 solution) have been investigated for their influence on numbers and functions of canine thrombocytes, leukocytes and erythrocytes. Infusion of banked blood and Ringer's lactated solution did not affect number and function of the thrombocytes, whereas the plasma expanders caused dramatic, but reversible decreases. Leukocyte numbers were also affected, but only gelatin resulted in a decrease of leukocyte function. No effect on erythrocyte numbers was observed. It is concluded that under these experimental circumstances some priming solutions cause acute intravascular aggregation. To obtain the optimal condition for studying the hemocompatibility of ECC, preferably Ringer's lactated solution should be used.


Anti-Ytb in pregnancy.

Anti-Ytb was readily eluted from the cord red blood cells of the second child of a mother with both anti-Ytb and anti-Kell in her serum. The baby was Yt (a+b+) and Kell negative. The cord red blood cells were found to have a weakly positive direct antiglobulin test. Clinically evident hemolytic disease of the newborn was not detected.


Potential danger of thrombosis after plasma exchange in the treatment of patients with immune disease.

Coagulation studies were serially performed before and after repeated plasma exchange in seven patients with myashtenia gravis. The fall in platelets and coagulation factor activities after plasmapheresis using a replacement material devoid of clotting factors was not so low that bleeding episodes were to be feared and no hemorrhages were observed. In contrast, thrombotic phenomena were suspected in two patients. Antithrombin III fell to undetectable levels in some cases. This finding associated with elevated values of factor VIII related antigen, factor VIII coagulant activity and von Willebrand factor suggested a potential danger of thrombosis in such treated patients.


Preparation of factor VIII concentrates by cryoprecipitate sedimentation.

A new method for factor VIII concentrate preparation is proposed. The method is the collection of cryoprecipitate after sedimentation at 4 C in a jacketed glass vessel. The final product is standardized (4.0 +/- 0.3 factor VIII units per ml) and can be infused in hemophilic patients regardless of their ABO blood type. Factor VIII recovery (52.2 +/- 6.4%) is comparable to other processes.


Problems with a walking donor transfusion program.

A walking donor transfusion program is outlined in detail. A total of 205 transfusions from 72 walking donors were given to 57 newborns in a Newborn Intensive Care Unit over a nine-month period. The average recipient weighed 1,762 g and the average transfusion was 15 ml of blood. Because a suitable walking donor was not always available when a transfusion was needed, 19 units of regular adult blood were also used to support the program. No immediate or delayed transfusion reactions were noted, but one fatal incident of serum hepatitis transmission occurred. Our experience suggests that a walking donor program carries an inherent significant risk of transmission of hepatitis and alternative methods with strict blood bank control are needed to assure maximum safety in neonatal transfusion.


Plasma protein fraction: the disappearance of kinin from the solution on storage.

The kinin produced when plasma protein fraction was heated at 60 C for 10 hours in order to inactivate the agent of hepatitis was shown to lose its activity during storage. There was an 80 per cent loss after three months and negligible activity was detectable after six months of storage. Synthetic bradykinin treated and stored under the same conditions showed no loss in activity.


Modulation of inhibition of the human mitogen response by methylprednisolone.

The in vitro response of human lymphocytes to phytohaemagglutinin was inhibited in a dose-related fashion by methylprednisolone added to the cell culture. The inhibition by steroid was 100-fold less than expected from published values of human lymphocyte receptor affinity. The dose response curve for inhibition was complex, frequently featuring a plateau region suggestive of a heterogeneous system, possibly caused by the presence of more than one subpopulation of cells. When lymphocytes were separated by unit velocity sedimentation, slow sedimenting lymphocytes were found to be highly steroid sensitive whereas rapidly sedimenting lymphocytes were steroid resistant. However, the addition of cultured macrophages rendered the steroid-sensitive fractions relatively steroid resistant. Similarly, unseparated peripheral blood lymphocytes at low concentrations were found to be highly steroid sensitive despite the addition of 2-mercaptoethanol. This sensitivity was lost by the addition of culture macrophages. Thus, macrophages play a vital role in the relative steroid resistance of human lymphocytes. No evidence was found that macrophages actually reduced steroid concentration in culture, and it is suggested that a cellular interaction is required to increase resistance to steroids.


Antithrombin III in fresh frozen plasma, cryoprecipitate, and cryoprecipitate-depleted plasma.

Antithrombin III (AT III) is a plasma protein that inhibits several activated procoagulants. Hereditary disease or acquired conditions such as severe hepatic dysfunction, nephrotic syndrome and intravascular coagulation may be associated with reduced levels of AT III. Its replacement may be essential in controlling thrombosis. In order to determine the most effective form of replacement, we compared AT III biological activity and antigen levels in conventionally prepared fresh frozen plasma, cryoprecipitate and cryoprecipitate depleted plasma (CDP). Both the activity and antigen levels were comparable in all three products (approximately 100%) and AT III was not concentrated in cryoprecipitate. These results indicate that conventionally prepared CDP, fresh frozen plasma and cryoprecipitate contain equal quantities volume for volume of AT III. On this basis, all products are equally effective as therapy for AT III deficiency, but CDP and fresh frozen plasma are recommended as convenient sources of this factor.


Demonstration of a dog liver immunosuppressive factor active in vitro.

These studies define the presence of an immunosuppressive factor in dog liver that is active in vitro. A crude dog liver extract was prepared by saline extraction and ultracentrifugation. In vitro immunosuppressive activity of the extract was assayed by its influence on standard phytohemagglutinin mitogen stimulation assays (PHA), two-way mixed lymphocyte culture (MLC) reactions, and primed lymphocyte culture (PLC). In six experiments with four extracts, the mean percentage of inhibition (MPI) of dog lymphocytes in PHA mitogen stimulation assays was 102.0 +/- 3.6. In two human MLC experiments, the extract produced an MPI of 102.3 +/- 0.3. In one canine MLC the MPI was 102.5. In three PLC experiments the MPI was 92.7 +/- 8.0, indicating that the extract inhibited sensitization. Cytotoxicity of the extract was shown not to be the mechanism of proliferation inhibition by restimulation of cells washed free of extract, concurrent eosin viability studies, and documentation of normal base proliferation of cells after extract was washed from them. We concluded that there is a naturally occurring immunosuppressive agent in dog liver that is active in vitro as demonstrated by inhibition of PHA MLC, and PLC cellular proliferation assays. The activity is not attributable to cytotoxicity.


Platelet glycolysis in platelet storage. III. The inability of platelets to utilize exogenous citrate.

The metabolism of exogenous citrate by freshly collected human platelets has been investigated by measuring the disappearance of citrate from platelet suspensions and by measuring the formation of CO2 and glycogen from purified radioactive citrate. These studies indicate that platelets do not have the capacity to metabolize exogenous citrate.


Mechanisms involved in the weak alloimmunogenicity of Thy-1 on mouse brain.

Immunization of mice with allogeneic brain homogenates fails to elicit an appreciable response to the Thy-1 antigen. The aim of the present study was to determine the mechanism of the low immunogenicity of allogeneic brain. Immunization of C3H mice with freshly prepared mixtures of AKR/J thymus cells with either AKR/J or C3H brain homogenates elicited a primary response to the Thy-1.1 antigen as effectively as immunization with AKR/J thymus cells. When the mixtures were incubated overnight prior to injection, only AKR/J brain homogenate but not C3H brain homogenate abrogated the capacity of AKR/J thymus cells to elicit an anti-Thy-1.1 response. Suppressor T cells did not seem to be responsible for the inability of brain to elicit an anti-Thy-1 response, as mice that received cyclophosphamide 2 days prior to injection of brain did not produce Thy-1 antibodies. Antigenic competition also did not seem to be the cause for the weak immunogenicity of Thy-1 on brain, as mixtures of thymus and brain were capable of eliciting a primary response. When spleen cells from mice hyperimmunized against Thy-1 were transferred to normal syngeneic mice, subsequent immunization with brain homogenate was capable of eliciting Thy-1 antibodies. These results indicate that Thy-1 on brain may resemble a hapten, in being incapable of eliciting a primary immune response, but behaves like a complete antigen in boosting a secondary response.


Use of dextran 150 as a macromolecular agent to improve granulocyte yields on the intermittent flow blood cell separator (Haemonetics Model 30).

Leukaphereses were performed on the intermittent flow cell separator (Haemonentics Model 30) using citrated dextran 150 as a macromolecular agent to improve separation of granulocytes. A mean of 1.77 X 10(10) granulocytes and 7.73 X 10(11) platelets were obtained without steroid stimulation and 2.65 X 10(10) granulocytes and 8.91 X 10(11) platelets were obtained with steroid stimulation of donors. There were no significant adverse reactions to dextran.


Cross-reactivity among the products of three nonallelic H-2 loci, H-2Ld, H-2Dq, and H-2Kk.

Cross-reactions of the products of three nonallelic H-2 loci, H-2K, H-2D, and H-2L, have been studied by serological, immunochemical, and cellular immune techniques. Immunoprecipitation experiments revealed a determinant shared between Ld and Dq molecules but absent on Dd molecules, By cytotoxic screening of sera from individual mice an exceptional anti-Ld serum was found which cross-reacted with an H-2k antigen. Genetic mapping studies suggested that the basis of this activity was an Ld-Kk serological cross-reaction. Cytotoxic T cells generated to Ld alloantigens were also found to recognize a cross-reacting Kk determinant. These studies therefore suggest that L, D, and K are three structurally homologous cell surface glycoproteins that have evolved from a common primordial gene.


Delayed hemolytic transfusion reaction caused by the second example of anti-K19.

A second example of anti-K19 has been identified in the serum of a black patient immunized by blood transfusions. The antibody was responsible for delayed hemolysis of transfused incompatible red blood cells. The patient's red blood cells are K:--19 but are otherwise of common Kell phenotype. The K19 antigen is closely associated with the Kell blood group although there is, as yet, no pedigree information to confirm that it is produced by the Kell gene. Tests on 10,757 group O blood donors have not revealed any further examples of the K:--19 phenotype.


Topographical distribution of Balkan endemic nephropathy in Serbia (Yugoslavia).

Topographical characteristics of 91 settlements affected by endemic nephropathy in Serbia--the region most frequently attacked by the disease--were analyzed and compared with the other known endemic areas in Yugoslavia. Numerical data were provided on the common characteristics of the affected villages--vicinity of a Danube tributary and low altitude. It was pointed out that only two endemic settlements lie above the altitude of 300 m. It is therefore suggested that investigation of the hydrogeological structure of these villages may provide valuable data, if an agent in water or soil is searched for.


The clinical and aetiological pattern of finger clubbing and hypertrophic osteoarthropathy in Nigerians.

A study of the clinical and aetiological patterns of finger clubbing and hypertrophic osteoarthropathy was carried out over a 15-year period. 116 patients were studied. Pain is not a common symptom in patients with finger clubbing and osteoarthropathy in Nigerians, contrary to what has been reported in the literature. The cause of finger clubbing is predominantly pulmonary in origin, being responsible in 84 per cent of cases. The commonest cause in bronchiectasis, followed by empyema thoracis, bronchial carcinoma and lung abscess. Among the nonpulmonary causes are infective endocarditis, endomyocardial fibrosis and cirrhosis of liver. Hypertrophic osteoarthropathy is found in 15 cent of the patients with finger clubbing, the commonest cause being carcinoma of the bronchus.


Endometriosis among the Hausa/Fulani population of Nigeria.

In three and half years at the Ahmadu Bello University Hospital, Zaria, Nigeria, endometriosis was found in 27 Nigerians (all negroid) and one Caucasian. Age and parity distribution were similar to what has been found in patients elsewhere. In other respects, there were striking differences. The frequency (8.2 percent) is one of the highest reported in the negro. Two fifths were menopausal, majority had associated pelvic inflammatory disease, and nearly all were in women of the lowest socio-economic status. The lesions were rare in the pouch of Douglas and were totally absent from the rectovaginal septum and in the extra peritoneal space.


Clinical and radiological features of neonatal septic arthritis.

Fourteen neonates (first 28 days of life) with septic arthritis were admitted into the neonatal unit of the University of Benin Teaching Hospital over a three year period. The incidence was 6.1 per 1000 admissions. Eight were fullterm, three preterm and two low-birthweight babies. Severe constitutional symptoms consisting of fever (temp. 39 degrees C), abdominal distension and jaundice were uniformly present. The aetiologic agents included Staphylococcus aureus (6), Proteus  mirabilis (2), and beta haemolytic streptococcus (1), no pathogen was isolated in five patients. There was a possible causal relationship between repeated traumatic femoral venepuncture of the hip in three infants. The early radiologic changes were deep soft tissue swelling, obliteration of fascial plances and widened joint space. Residual damage of the hip joint was noted in one neonate; four died. It is suggested that toxic-looking new-born infants, suspected of septicaemia by examined radiologically for possible arthritis.


Frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in Tanzanian males with typhoid fever.

The frequency of G-6-PD deficiency in the Dar es Salaam male population is given as 18.7%. In this preliminary study, is reported a frequency of 45% in males with typhoid fever--a figure more than twice the prevalence in the general Dar es Salaam male population. Possible reasons for positive correlation between the two disease states are described.


Serological evidence of dengue virus activity in children on the Northern Leeward Islands (Netherlands Antilles).

An arbovirus serologic survey of school children on the Northern Leeward Islands (Saba, St. Eustatius and St. Maarten) using haemagglutination inhibition (HI) detected a high proportion of reactors to dengue types 1,2, and 3. Analysis in relation to age showed an increasing proportion to be positive with increasing age. The results of an all-age survey on St. Eustatius 1970 led to the hypothesis of possible dengue serotype 1 activity on St. Eustatius around 1900, whilst it is thought that dengue type 2 was endemic at other times. In view of the continuous high endemic dengue activity the (re)-appearance of dengue serotype 1 next to type 2 and 3 may be the prelude to the occurrence of the dengue shock syndrome.


Haemoglobin and erythrocytic glucose-6-phosphate dehydrogenase variants among selected tribes in Western Saudi Arabia.

638 subjects from six tribes in Western Saudi Arabia were tested for haemoglobin and G-6-PD variants. In the bedouins of Harbi and Sahafi tribes there was no sickling but a low frequency of both G-6-PD deficiency (1.7%) and the Gd A+ variant (1.7%) in Harbi. In Mograbi and Mowallad tribes who immigrated recently from Africa, the frequency of Hb S was 4.1 and 3.5%, G-6-PD deficiency 7.5 and 8.5% and the Gd A+ variant 15.1 and 8.5% respectively, which are higher than in bedouins. In Ghamid tribe 4% had Hb S and there was a low frequency of both G-6-PD deficiency (4.8%) and Gd A+ variant (1.6%). However a new B slow variant is common among the Ghamid (16.1%). Hb S frequency in Zahran tribe was 2.6%. Six of the 12 g-6-PD deficient (screening) were found to be positive on starch gel electrophoresis.


Unusual manifestations of mycetoma.

Five cases of mycetoma of bone involving patella, shaft of tibia, medial malleolus, calcaneum and phalanx of great toe are presented. In all the cases bones were extensively damaged with minimal or no involvement of soft tissue, a very unusual feature. Aetiopathogenesis involvement of bone substantiated by facts, is discussed.


Hookworm in dogs and cats in the area of Jakarta.

An investigation of the distribution and prevalence of hookworms in dogs and cats was carried out during the year 1976 in the area of Jakarta. Sixty-eight percent of the dogs harboured A. caninum, whereas 37% harboured A. ceylanicum and 18% A. braziliense and 32.1% as A. ceylanicum. Hookworms were recovered from 78% of the fifty cats; 72% of the cats were infected with A. braziliense and 24% with A.ceylanicum. Among the 1895 hookworms in cats, 73,5% were A. braziliense and 24.5% were A. ceylanicum. Only one female A. tubaeforme was found in one cat.


A new leptospiral serovar in the Australis serogroup.

A new serovar in the Australis serogroup is described after parallel investigations by the "classical" comparative cross-agglutinin absorption test method and by a method derived from factor analysis. The serovar name ramisi with reference strain Musa is proposed.


The occurrence of leptospiral antibodies in rural inhabitants of Argentina.

Sera collected during surveys of presumably healthy rural inhabitants of the Provinces of Corrientes and Neuquén, Argentina, were examined for serological evidence of leptospirosis. Significant antibody levels (1:100 or greater) were found in 8.7 per cent of 1,029 sera from residents of Corrientes Province. The most frequent reactions occurred against the serotypes australis, hebdomadis group, pomona, and icterohaemorrhagiae. The predominance of antibodies to the Australis group in the country is new and suggests the emergence of leptospirosis in an unrecognized animal reservoir host. Out of 706 sera collected from rural school students and sera from 71 adults in the Province of Neuquén, only 4 (0.5%) showed leptospiral agglutinin in the microscopic agglutination test and these were only at a 1:100 serum dilution. The higher percentage of reactors in the Corrientes population appears to reflect a more favorable environment and a greater risk of infection.


Contamination of some fermented Nigerian beverages by carcinogenic nitrosamines.

A survey to determine the extent of the nitrosamine contamination of some popular fermented Nigerian beverages by dimethyl- and diethylnitrosamine has been carried out in the Lagos, Ogun, Oyo, Ondo, Kwara and Benue States of Nigeria, following the mass spectrometric detection of these carcinogens in palm wine and nono (sour milk). The indication is that the contamination of the drinks, namely, palm-wine, nono, pito, burukutu, and ogogoro, by both nitrosamines is widespread and occurs at the part per billion level. 0.6 - 22 mu g nitrosamine/l was found by routine thin layer and gas liquid chromatographic methods using authentic nitrosamines as reference standards. Because of the widespread contamination of the test beverages by dimethyl- and diethylnitrosamine, and the usually frequent occurrence of nitrosamine precursors in nature, it is presumed that these potent and versatile carcinogens could play a significant role in the formation of human cancers in the Nigerian population.


A population study in the Maldive islands.

The Maldive Islands harbour, among 2,000 widely scattered coral islands, 190 atolls at present inhabited by over 128,000 persons. Between 1956-1976 the Royal Air Force occupied an air staging station which resulted in an increase in material and health prosperity, mostly affecting Hittadu Island. The growth rate which was 2.6% for the Maldivian population prior to that period, increased to 4.4%, resulting in a population density of 1,085 per sqkm. The unenviable prospects of the withdrawal are described.


Leptospirosis acquired in Surinam.

A case of leptospirosis seen in the Netherlands but acquired in Surinam is described. Marked jaundice, disturbance of renal function, a first degree atrioventricular block and pancreatic irritation were observed.


Blastomycosis treated successfully with miconazole.

A case of disseminated blastomycosis is described, which was treated with miconazole orally. A rapid cure was achieved without side effects. Miconazole seems to be effective and safe in the treatment of blastomycosis.


Granuloma inguinale in Botswana.

Description of the probably first case of granuloma inguinale in Botswana and result of treatment.


Machakos Project studies. Agents affecting health of mother and child in a rural area of Kenya. XIII. Spatial contagion in measles epidemics.

The Machakos Project has yielded data by which it is possible to analyse spatial aspects of contagion in measles epidemics. Problems of geographical scale and interaction patterns occlude the spatial factor and rather different spectra of outbreaks were seen when the data are analysed at sub-location level. The likely patterns of spatial contagion are indicated and the need for smaller-scale study is pointed out. The role of secondary infection is considered and two proposed approaches to mathematical simulation are briefly discussed.


[Ultrastructure of the DNA-synthesizing cells of the sinoatrial node in mouse embryos according to electron microscopic autoradiographic data].

By means of electron microscopic autoradiography with 3H-thymidine a study was made of the differentiation degree of DNA synthesizing muscle cells in the sinoatrial node (SAN) of the heart conductive system of the 18 day old mouse embryos. Clear myocytes (CM), predominating in the SAN at this stage, are irregular in shape, with interdigitating protrusions. Nuclei are clear, spherical or ellipsoidal. One hour following 3H-thymidine injection, about 6% of CM display labeled nuclei; this index is considerably lower than in working ventricular myocardium. Like unlabeled myocytes, CM being in phase S contain sparse, randomly located thin myofibrilles. In some areas of the sarcoplasm, only myofilament bundles and Z-disk material can be seen. The number of CM myofibrilles is always considerably less than in the working ventricular myocytes. Accumulations of intermediate (8--11 nm) filaments are present. Mitochondria with a few cristae are not numerous. The sarcoplasmic reticulum and Golgi apparatus being relatively well developed, multivesicular bodies, centrioles, and occasional cilia are often seen. Near the centrioles (basal bodies), striated filamentous bundles are found sometimes showing periodic dense lines separated by 50--70 nm. Specialized contacts between CM are rare, being presented only by desmosomes and primitive intercalated discs. Besides CM, sparse small dark cells occur filled with myofibrilles and mitochondria. In the peripheral regions of the node "transitional" cells are seen. The SAN of the 18 day old embryo mouse heart grown due to proliferation of CM with a poorly developed myofibrillar apparatus.


[Light and electron microscopic study of the mitochondria in human embryonic nervous tissue cells in vitro].

After a 5-min heating of isolated Tradescantia leaves at 49 degrees C the granular component in the nucleoli of parenchyma cells disappears and the nucleoli grow more compact and exclusively fibrillar in structure. Simultaneously, the ability of chloroplasts of these cells for phototaxis is completely inhibited. In leaves placed in a moist chamber at room temperature 48 h after heating a normal ultrastructure of nucleoli and the ability of chloroplasts to respond by phototaxis to change in illuminations are restored almost synchronously.


[Low-molecular RNA subcellular localization and its binding strength with cellular structures].

Some fractions of low molecular weight (LMW) nuclear RNAs were shown to be present in the cytoplasm of rat liver cells. In addition to known 4S tRNA, 5S and 5,8S rRNAs U3 and 8S1 LMW nuclear RNAs, 8SII and 8SIII LMW RNAs have been detected in RNA preparations of free total and membrane-bound polysomes. The U3 and 8SI polysoma I RNAs seem to be associated with high molecular weight polysomal RNA. Using thermal phenol fractionation, that some LMW RNAs were shown to be slightly bound to the cellular structures whereas some others are bound more tightly. Considerable amounts of LMW RNAs are tightly bound to the chromosome-nucleolar apparatus. They can be extracted only at 85 degrees C. The data presented are discussed with regard to LMW nuclear and polysomal RNAs functions.


[Kinetic study of a heterogeneous tumor cell population using a mathematical model].

A mathematical model of a heterogenous tumor as a system of interrelating cell populations is described, including a pool of quiescent cells, cell-to-cell variability in maturation rates, and cell migration from growth area to necrotic one. Computer simulation results are given, model labeled mitoses and labeled index curves for the Lewis carcinoma are compared with experimental data.


[Subcellular localization of low-molecular RNA in the cells of chick embryos].

The subcellular distribution of chick embryo low molecular weight RNAs has been studied by the thermal phenol fractionation procedure. The major part of 8SII RNA, earlier discovered in some oncornaviruses and normal cells, was extracted by phenol at 4%. Our results thus give evidence of the cytoplasmic localization of this RNA. Another part of 8SII RNA, which has been extracted at 65 degrees, is thought to consist of newly synthesized molecules located in the nuclei. A similarity in subcellular distribution of low molecular weight RNAs from chick embryo and rat liver has been obtained, i. e. such a distribution may be of universal nature.


[Effect of low-molecular nonelectrolytes and hypotonia on the contractile responses of frog sartorius muscles].

The potentiation of contractile responses during prolonged incubation of frog sartorius muscles in a conventional Ringer solution and in a calcium-free Ringer solution which contained 400 mM of urea, acetamide or ethylene glycol was observed when stimulation with single electric impulses and with caffeine was carried out. When the muscles were exposed to a hypotonic solution the reduction in the amplitude of caffeine contractures or their complete disappearance were registered, whereas the electrical stimulation of muscles in the same medium exerted an increase in the amplitude of contractile responses. The addition of 400 mM glycerol to the hypotonic solution caused an increase in the amplitude of contractions under both types of stimulation.


[Cellular capacity in tissue culture and in tumors for recovery from the injuries induced by N-methyl-N-nitrosourea].

The survival of the LL cell line in the log-phase of growth, and clonogeneic ability of NKLy/LL tumours, derived from a subcutaneous transplantation of these cells to mice, have been investigated. The survival assay of culture cells and cells in tumours was studied both immediately, and 6--72 hours after the treatment with N-methyl-N-nitrosourea (MNU) in concentrations of 0.05 mg/ml in vitro, and of 12.5--200.0 mg/kg injected in vivo. No repair of potentially lethal damages was noticed in tissue culture during a 72 hours incubation in conditioned medium after the MNU treatment, or in small NKLy/LL tumours when analysed 24 hours after the drug injection. Possible mechanisms of an irrepairable damage induction are discussed.


[Myofibril breakdown during spreading damage. III. Isolated rat muscles].

Ultrastructural changes have been studied in fast (EDL) and slow (SOL) isolated muscles of rats during Zenker's degeneration (ZD). The general pattern of ZD is similar in both the muscles and proceeds in the same way as in the fast skeletal muscles of amphibians: vacuolation of the T-system and of the sarcoplasmic reticulum occur prior to necrosis, and then contraction knots are formed. The latter detach from the rest of the fiber, and myofibrils degrade into clots of electron dense material. Differences in the development of ZD in this muscle are as follows: vacuolation is more strongly pronounced in EDL, contraction and supercontraction of sarcomeres being more characteristic of SOL. In this ZD region of both the muscles, additional membranes are found in some intracrystal spaces of mitochondria, this phenomenon occuring more frequently in SOL. Selective lysis of the Z-line during ZD has been detected only in single EDL Fibres.


[Action of heavy water on actomyosin pellicular filaments].

Deuterium oxide (D2O) prolongates the contractile ability of actomyosin threads by 85%. The contraction of actomyosin threads decreases in the presence of D2O by 28%. D2O decreases neutral red sorption by actomyosin threads. The limiting dye sorption (A infinity) decreases by 45 and 31% within the ranges of weak and high concentrations, resp. Thus, deuterium oxide may affect the conformation of protein molecules.


[Cytogenetic analysis of human oocytes and the process of their maturation outside the body].

A cytogenetic analysis of human oocytes, after their removal from follicles and during extracorporeal maturation, has been performed. The heterogeneity of follicular oocytes according to the character of nuclear chromatin was established. It is probably related to the rate of reinitiation of meiosis in vivo and to the rate of atretic process. The dynamics of human ovum maturation in vitro was studied. 50.8% oocytes reached metaphase II in 46 hours of cultivation, but only 22.8% of these had no chromosomal aberrations. It is supposed that the high rate of chromosomal anomalies in vitro is a possible consequence of degenerative changes of oocytes that started still in vivo.


[Factors controlling the recirculation of hematopoietic stem cells. IV. The effect of thymosin on the migration and differentiation of hematopoietic stem cells].

Thymosine, a thymus hormone, restores the thymectomy induced deterioration of the routine pathways of migration and differentiation ofhemopoietic stem cells in mice. Administration of thymosine together with bone marrow cells from thymectomized mice to irradiated recipients also restores the level of migration and differentiation of hemopoietic stem cells. The inducing effect of thymosine on the maturation of T-lymphocyte precursors, which in their turn restore the usual rate of migration and differentiation of hemopoietic stem cells, has been suggested.


[Clonogenic fibroblast precursors among the peritoneal fluid cells of guinea pigs].

There are about 2000 (1830 +/- 360) clonogenic precursors of fibroblast (CFU(f)) in the peritoneal liquid of guinea-pig, which form colonies (clones) in the monolayer cultures. The colonies consist of actively proliferating fibroblasts with different morphology. The proportion of colonies with different morphology shows changes during the growth of cultures. During aseptic inflammation the number of CFU(f) in the peritoneal liquid increases by 25, 15 and 4 times after 6 and 24 hours and 3 days, resp., compared to the control. 99% CFU(f) does not proliferate in situ, and the increase of the number of CFU(f) after inflammation is not followed by their proliferation. The irradiation of the peritoneal cavity killed the most of CFU(f)--97-99%. During the aseptic inflammation, the number of CFU(f) increased to 470 +/- 105 during 4 days after the irradiation, which is 5% of the number of CFU(f) on the 3rd day of inflammation for the non-irradiated animals. Thus, no intensive repopulation of clonogenic precursors of fibroblasts occurs in the peritoneal cavity.


[Change in the karyotypic structure of mouse and rat rhabdomyosarcomas on their transplantation into the anterior chamber of the eye].

A study has been made of 7 transplatable lines of mice rhabdomyosarcomas and one line of rat rhabdomyosarcoma during their transplantation into the eye anterior chamber subcutaneous tissue. In all, 10 subcutaneous transplants and 15 transplants into the eye anterior chamber (EAC) were examined. Etanol fixed print smears were subjected to the Feulgen reaction to measure the DNA content using a cytophotometer MCPhU-1; 100 cells being measured in each transplant. In the majority of the EAC transplants, a statistically significant decrease of the karyotypic variability was found in additionto the augmentation to the diploid cell ratio as compared to subcutaneously proliferating populations of the same tumour lines. In some cases EAC transplants displayed exclusively diploid (periploid) populations of tumour myoblasts. Shifts in the karyotypic structure of populations towards diploidy, revealed during the cultivation of transplantable rhabdomyosarcomas, may be regarded as a phenomenon of the "karyotypical normalization" of tumour cells. The disappearance or sharp decrease of tetraploid or hypertetraploid classes of cells in EAC transplants may be due to the increase of their selective value in condition of immunological privilege of diploid, karyotypically normal cells, and of reduction of the genome mutation frequency in a diploid fraction of tumor myoblast populations.


[Analysis of the cellular interaction of 2 transplantable lines in mixed culture].

A relationship between two transformed cell lines (L and HEp-2) has been studied at different population densities. L cells were inhibited at a low, but not at a high density. We noted specific cell structures in mixed culture at a low density. Crowded cells did not form such structures at the same conditions. Possible alterations of L cells are discussed.


[Ultrastructure of the interstitial cells of the renal papilla in the white rat].

Interstitial cells of the renal papilla have the phenotypic appearance, being more of a fibroblast than of a histiocyte character. Interstitial cells differ from the "typical fibroblasts" in the number of lipid droplets, in the development of cisternae of the Golgi complex and rough endoplasmic reticulum, and in the number of lysosome-like bodies and mitochondria.


[Effect of different sera on amniotic cell growth in culture].

The growth properties of the FCS (calf foetus serum), obtained from the blood of died fetals have been investigated, the "Gibco" FCS and human serum IV being used as a control. It was shown, that FCS prepared in our laboratory provided the growth and karyotyping of amniotic cells in vitro. This FCS was equally effective for cell planting as was human serum IV and somewhat less effective than the "Gibco" FCS. The FCS obtained in our laboratory is not deficient, and cheap. It may be recommended for a wide use in prenatal detection of genetic disorders.


The economic effects of trypanosomiasis in sheep and goats at a range research station in Kenya.

A study on the economic effects of naturally acquired trypanosomiasis in sheep and goats over a period of 35 weeks under range conditions in the Kiboko area of Kenya indicated that the financial loss from reduced weight gain and death amounted to 36.2 and 62.9 Kenya shillings per head for goats and sheep respectively. This was derived from the weight loss through death together with the reduced weight gain of the survivors compared with treated animals. The study also compared the efficacy of 3 drug regimes in goats and suggests that although quinapyramine (prophylactic) B.vet.C. provided the longest protective period, the weight increase of the stock under isometamidium chloride treatment was higher. The benefits of the drugs used are discussed.


Studies on the epidemiology of trypanosomiasis in sheep and goats in Kenya.

The epidemiology of trypanosomiasis in a tsetse-infested range area of Kenya was studied for 2 years in various breeds of sheep and goats. Observations, including infection rates, PCV, temperature and weight loss indicated that the exotic breeds were more susceptible to natural trypanosomal infection than the indigenous breeds and that the infection may be severely debilitating and in many cases fatal. Observations of tsetse numbers and rainfall in the grazing area during the first year showed that there was a significant correlation between tsetse numbers and rainfall of the previous month. The increase in tsetse numbers, which occurred one month after substantial rainfall, was followed by an increase in the prevalence of trypanosomiasis in the animals. However, during the second year when rainfall was low there was no correlation between tsetse numbers and rainfall. It was concluded that the seasonal incidence of trypanosomiasis and the possible trypanotolerance of the indigenous breeds are important factors to be considered when initiating a small stock improvement programme for trypanosomiasis-endemic areas.


Studies on the livestock of Southern Darfur, Sudan, VII. Production of poultry under simulated traditional conditions.

Observations were made on egg production, egg hatchability and fertility, liveweight and growth characteristics of domestic fowls, Muscovy ducks and pigeons kept under simulated traditional conditions in Southern Darfur. Fowl and ducks produced about 50 eggs a year in 4 1/2 clutches spaced at 80 day intervals and pigeons 17 in 8 1/2 clutches at 43 day intervals. First eggs were laid at about 240 days by the fowls, 213 days by ducks and 132 days by pigeons. The annual weight of eggs produced was 2,013 3,596 and 286 g for fowl, ducks and pigeons respectively, being 1.53, 2.33 and 0.88 times the mean adult female body weight for each species. Fertility and hatchability of eggs were higher in fowls than ducks which were in turn higher than in pigeons. Early growth in pigeons was very rapid. Muscovies achieved mature body weights at about 20 weeks while mature weights in fowls were achieved much later in males than in females.


Ovine facioliasis (Fasciola gigantica) on the Ahmadu Bello University farm.

Outbreaks of fascioliasis (Fasciola gigantica) in sheep were observed on the Ahmadu Bello University farm during the end of the dry season in 1972-74 and in 1978. During 1972 especially the pregnant ewes were affected. Pre- and post-mortem exmaination of the affected sheep showed typical signs of acute fascioliasis; the number of flukes in the liver ranged between 77 and 239. The infections were acquired when the animals grazed near the man-made lake on the farm. A limited snail survey revealed the presence of Lymnaea natalensis with the highest incidence of snails as well as of larval Fasciola infections in the snails during the beginning of the dry season. There was an indication that the control measures taken after 1974, i.e. not allowing the animals to graze around the lake especially during the wet season, prevented the occurrence of outbreaks in 1975-77.


Efficacy of oxfendazole against naturally acquired gastro-intestinal nematode infestations in buffaloes in Egypt.

The benzimidazole anthelmintic, oxfendazole, was used as an oral suspension at 4.5 and 2.8 mg/kg to treat naturally infested indigenous buffaloes in Egypt. Worms of the genera Haemonchus, Cooperia, Trichostrongylus, Ostertagia, Chabertia and Oesophagostomum were identified in the animals prior to treatment. A 100% reduction in faecal egg counts was obtained at the 4.5 mg/kg level when compared to untreated control animals. Reductions in faecal egg counts greater than 90% were recorded at 2.8 mg/kg and these exceeded reductions obtained by drenching with the older benzimidazole anthelmintic, thiabendazole, at 67 and 111 mg/kg.


The response of Awassi and Merino sheep to primary infection with Haemonchus contortus.

The possible existence of breed differences in the response of sheep to primary infection with Haemonchus contortus was examined by comparing worm establishment and pathogenic effects of the parasite in Awassi and Merino sheep of haemoglobin type B infected with 500 third stage H. contortus larvae per kg body weight. The results showed that the Merino sheep had lower faecal egg counts and worm burdens and suffered less severe clinical disturbances than sheep of the Awassi breed. This suggests that genetic resistance operates primarily at the level of worm establishment.


Cell counts in bulked milk supplies from dairy farms of northern Nigeria.

Somatic cells in 596 milk samples collected from bulked supplies of 3 northern Nigeria dairy farms were counted by an electronic method following a standard method for the preparation of the milk samples. Mean somatic cell counts per ml indicating low level of infection were 158,597, 166,742 and 155,032 for the 3 farms, without any significant differences. Mean somatic cell counts per ml indicating herd mastitis averaged 354,768 +/- 66,348 and the pathogenic organisms isolated were Escherichia coli and Staphylocucus aureus. Counts useful for future regular monitoring of somatic cells in bulked milk supplies in northern Nigeria are presented.


Effect of thiabendazole and tincture of iodine on cattle ringworm caused by Trichophyton verrucosum.

Clinical trials were carried out on 3 groups of 30 Friesian cattle naturally infected with Trichophyton verrucosum. One group was treated with 3.75% thiabendazole in glycerine, another with 5% tincture of iodine and the last served as the control group without any treatment. Both the preparations were applied locally on the ringworm lesions at 3 day intervals with a total of 4 applications. The percentage of animals cured was 86.7 by thiabendazole and 46.7 by tincture of iodine. No recrudescence was observed during the subsequent 4 months period.


The prevalence of brucellosis among sheep and goats in northern Iraq.

Out of a total of 2,368 sheep and 3,156 goats tested against brucellosis by the Brewer's card test in the 5 Mohafadhas of the northern region of Iraq, 0.93% and 4.4% respectively were recorded as positive reactors. The highest incidence (1.36%) among sheep was found in the Kirkuk region while the lowest (0.78%) was in the Mosul (Nineveh) region. Among goats the highest incidence (11.55%) was revealed in the Dukho region while the lowest (1.47%) was in the Sulaimaniya region. The need for more detailed work on the incidence and on the isolation of the local strains, as well as the need for a control programme, is also discussed.


A computer-aided three-dimensional display system for ultrasonic diagnosis of a breast tumour.

This paper describes a three-dimensional (3-d) display method by which the shape of an abnormal tissue, say, a breast tumour is represented as a line picture on a cathode ray tube (crt). The 3-d image consists of a set of overlaid contour lines, each of which shows the boundary of the tissue and is obtained from the corresponding B-scan digitized image by using image processing techniques such as smoothing and Laplacian. The system together with the 3-d algorithm is explained and some of the experimental results and pertaining problems are discussed.


Effect of intermittent exposure to 3% CO2 on respiration, acid-base balance, and calcium-phosphorus metabolism.

One subject was exposed for six days to increasing levels of CO2, rising at a constant rate from 0.03 to 3.0% CO2 within a 15-h period followed by 9 h of air breathing. To assess acid-base parameters, arterialized capillary blood was taken from a finger twice daily (at 8 a.m. and 11 p.m.) at times corresponding to the beginning and end of the intermittent exposure to CO2. Venous blood samples were obtained on alternate days at the same times. Urine specimens were collected twice daily. The subject was on a liquid diet. Resting respiratory minute volume (VE), oxygen consumption (VO2), carbon dioxide excretion (VCO2), alveolar carbon dioxide and oxygen tension (PACO2) and PAO2) were measured twice daily. PACO2 and PAO2 were also determined at the end of breath-holding twice daily; CO2 tolerance tests and lung function tests were also carried out. In contrast to the effects of chronic exposure to 3% CO2, the CO2 tolerance tests showed an increased sensitivity (increase of slope) and breath-holding PACO2 did not change, indicating that acclimatization to CO2 did not develop. The ventilatory response to CO2 was not sufficient to prevent CO2 accumulation in the body; this accumulation was eliminated during the nightly air-breathing periods on the fourth and fifth days, indicated by higher values of PaCO2 and PACO2. The known renal response to hypercapnia, consisting of an increased excretion of titratable acidity, ammonia, and hydrogen ion excretion, occurred but was interrupted after the first day and was triggered again on the fourth and fith days when accumulated CO2 was released from body CO2 stores. The second renal response was associated with a marked calcium excretion, which suggests that bone CO2 stores were involved.


Proliferation of pneumocyte II cells in prolonged exposure to 1% CO2.

Guinea pigs were exposed to 1% CO2 in a mixture of 21% O2, balance N2 and were killed at weekly intervals, together with control animals housed in the same type of environmental chamber and exposed to normal ambient CO2. The exposed animals showed a persistent elevation of PaCO2, averaging about 4 mmHg, and a small decrease in pH (-0.04 units). During the whole exposure period standard bicarbonate remained 1-1.5 mEq below control levels, indicating a failure of the kidney to increase bicarbonate reabsorption. Electron microscopic studies after 4 and 6 weeks of exposure to 1% CO2 showed ultrastructural changes of the lungs, consisting of marked increases in the size and number of pneumocyte II cells that were still present two weeks and to a lesser extent four weeks after recovery. Changes in the pneumocyte II cell were postulated to be compensatory reactions to impairing CO2 effects on the alveolar lining cell (Type I cell).


Physiological stresses related to hypercapnia during patrols on submarines.

Physiological studies on hypercapnic effects carried out on 13 Polaris patrols are summarized. The average CO2 concentrations ranged from 0.7-1% CO2; CO2 was identified as the only environmental contaminant of the submarine atmosphere that has a direct effect on respiration in the concentration range found in the submarine atmosphere. A comparison has been made of physiological effects produced during 42 days of exposure to 1.5% CO2 during laboratory studies (L.S.) with those observed during 50 to 60 days of exposure to 0.7-1% CO2 on patrols (P.S.). A close similarity was found in the effects on respiration and blood electrolytes under both conditions. Respiratory minute volume was elevated by 50-63% because of increased tidal volume. The physiological dead space increased 60%. Vital capacity showed a trend toward a decrease. Studies of acid-base balance carried out during patrols demonstrated cyclic changes in blood pH and bicarbonate; pH and blood bicarbonate fell during the first 17 days of exposure, rose during the subsequent 20 days, and decreased again after 40 days. These cycles cannot be explained on the basis of known renal regulations in CO2-induced acidosis and were not found during exposure to 1.5% CO2. The hypothesis is advanced that these changes in acid-base balance are caused by cycles in CO2 uptake and release in bones. The time constants of the bond CO2 stores fit the observed length of cycles in acid-base balance. Correlation with cycles of calcium metabolism provides further support for this hypothesis. Red cell electrolytes showed similar changes under 1.5% CO2 (L.S.) and 0.7-1% CO2 (P.S.). Red cell sodium increased and potassium decreased. Moreover, red cell calcium also increased under both conditions. The significance of these red cell electrolyte changes in regard to changes in permeability and active transport remains to be clarified. An increased gastric acidity was found during patrol (exposure to 0.8-0.95% CO2). The changes observed during patrols disappeared during the recovery periods.


Effect of prolonged exposure to 0.5% CO2 on kidney calcification and ultrastructure of lungs.

Guinea pigs were exposed for up to 8 weeks to 0.5% CO2, 21% O2, and balance N2. Control groups of the same age were kept simultaneously in environmental chambers on air. A slight increase in PaCO2 and decrease in pH were observed at various periods of exposure to 0.5% CO2. After eight weeks of exposure, an increased kidney calcification, indicated by increased kidney calcium content, was found. Plasma calcium was significantly elevated at this point, apparently because of the release of calcium from bone. After 8 weeks of recovery on air that followed 8 weeks of exposure to 0.5% CO2, values had returned to control levels. No significant ultrastructural changes were found in the lungs after 4, 6, and 8 weeks of exposure to 0.5% CO2.


Vision of submariners.

A variety of vision tests have been administered to submariners over the years. The results show that the average submariner, though maintaining a normal, healthy visual system, has distant acuity somewhat below normal and manifests more myopia, esophoria, and less accommodative power than men of comparable age, as documented in the literature. The reasons for these changes are unknown but probably involve confinement; whether confinement peculiar to the submarine of the "confinement" of urban living is the more important for these changes is discussed.


Attitude changes during and after long submarine missions.

To assess the kind and degree of attitude changes occurring during a 2-month submerged mission, two enlisted crews of one fleet ballistic missile submarine (FBM) (n = 101 each) were administered the Submarine Attitude Questionnaire before and after two 55-day submerged missions interspersed with a rehabilitation period of the same duration. Results showed that time-in-service and pay grade bore a U-shaped relationship to positive attitudes toward the service. During submergence, most attitudes became negative and then reversed polarity during rehabilitation. However, there were no cumulative effects upon attitudes during successive missions. Attitudes pertaining to the realities of the mission (for example, boredom, hazardous aspects) became more negative but recovered faster. On the other hand, attitude changes related to long-range expectancies in terms of goal achievement of the crew members were less likely to recover. Several possible explanations for these attitude changes are discussed in the context of the mission of the FBM submarine. Suggestions for preventing or alleviating untoward attitude changes during long submarine missions are also presented.


Biochemical and hematologic profiles of 1000 submariners.

Control biochemical and hematologic data were gathered for 1017 healthy submariners who ranged in age from 19.5 to 43.5 years. Means, standard deviation, and frequency distribution are presented for 24 whole blood and serum variables and, where appropriate, for 11 urinary variables. After statistical separation of the effects of aging and length of submarine service, it has been determined that the following correlations were significant in this sample: neutrophil and leucocyte levels, serum cholesterol, and both fasting and postprandial glucose correlated positively with age; serum alkaline phosphatase levels and age correlated negatively. Age-corrected positive correlations were demonstrable between length of submarine service and both serum cholesterol content and alkaline phosphatase activity; after a loading test, glucose levels showed a negative relationship to length of submarine service. Split-sample correlation analyses verified these significant correlations, with the exception of the apparent rise in alkaline phosphatase activity with increasing length of submarine duty.