Prevention by tiopronin (2-mercaptopropionyl glycine) of methylmercuric chloride-induced teratogenic and fetotoxic effects in mice.

Previous investigations (Fuyuta et al., '76, '79) have shown that a single oral administration of 25 mg/kg methylmercuric chloride (MMC) to pregnant ICR mice on day 10 of pregnancy induced cleft palate in a remarkably high incidence in fetuses. Based on these findings, the present study dealing with the prevention of cleft palate by Tiopronin, (2-mercaptopropionyl glycine, Tp), was initiated. Twenty females in the positive control group were given 25 mg/kg MMC orally on day 10 of pregnancy and then given physiological saline intraperitoneally. Twenty females in the negative control group were given distilled water orally and then given saline intraperitoneally. Cleft palate was found in 98.1% of fetuses in the positive control group and none of them in the negative control group. Twenty females were pretreated with a single oral  dose of 25 mg/kg MMC on day 10 of pregnancy and were posttreated with Tp intraperitoneally, immediately and at every 24, 48 and 72 hours after the MMC treatment. The doses of Tp were 320, 160 and 80 mg/kg/day. The incidences of cleft palate in fetuses were reduced to 1.49, 31.3 and 47.8% in the Tp-treated groups with the doses of 320, 160 and 80 mg/kg/day, respectively. Tiopronin could effectively prevent the expected incidence of cleft palate. Other types of abnormalities as well as fetotoxicity represented by reduced fetal body weight were also effectively prevented with the Tp-treatment.


Muscular and other abnormalities in a case of Edwards' syndrome (18-trisomy).

This paper describes the anatomical variations observed in a specimen exhibiting Edwards' Syndrome (18-trisomy). The clinical and autopsy data are compared with those reported in earlier literature. Aside from having a tracheoesophageal fistula, the viscera were characterized by abnormalities of the heart, lungs, liver and kidneys. The facial musculature was relatively undifferentiated. Only a few abnormalities were recorded in the otomandibular and suprahyoid structures. The infrahyoid region had three pairs of supernumerary muscles, including the "sternohyoideus azygos." The bluk of abnormalities were found in the muscles and nerves of the upper limb. These included the absence of the palmaris longus and brevis, the subclavius and the extensor digiti quinti proprius; the presence of supernumerary muscles, e.g., the "rhomboideus occipitalis," the "latissimocondyloideus," and the "subclavius posticus." The deltoid and the pectoralis major were fused to form the "deltopectoral" complex. A definitive musculocutaneous nerve was found in the right arm only. In the lower extremity supernumerary muscles included the "tenuissimus," "peroneus quinti digiti," and the "extensor primi internodii hallucis."


Aspirin: teratogenic evaluation in the dog.

Beagle bitches were administered aspirin at either 100 or 400 mg/kg/day between Days 15 and 22 or Days 23 and 30 postmating, and corresponding control groups were dosed with vehicle during one of these same time periods. Maternotoxicity was evident in all dogs dosed with 400 mg/kg/day of aspirin, but no signs of toxicity were observed when 400 mg/kg/day of aspirin was administered from Days 15 to 22 postmating. Teratogenicity, as evidenced by 50% malformation rate, was seen in fetuses from dams treated with 400 mg/kg/day on Days 23 to30 postmating. Observed malformations included, but were not limited to cleft palate,micrognathia, anasarca, cardiovascular malformations, and tial anomalies. No evidence of embryotoxic or teratogenic effects was seen in fetuses from either 100 mg/kg/day dosage level group. Examination of fetuses from 12 untreated litters and 4 vehicle-control litters revealed a very low spontaneous malformation rate confined almost entirely to minor tail abnormalities. These data support use of the dog as an acceptable alternative species in teratogenic screening.


Hemodynamic changes following ventricular aneurysmectomy during the first three postoperative days.

One hundred twenty-eight patients underwent left ventricular aneurysmectomy; in 78 cases the procedure was combined with either aortocoronary bypass or valve replacement. In 7 patients undergoing isolated aneurysmectomy the influence of atrial pacing on various hemodynamic parameters was studied immediately postoperatively and on the first, second and third postoperative days. Until a certain point, increase in heart rate resulted in decrease of left ventricular filling pressure and increase of cardiac output, while systemic pressure changed only slightly. For each patient and each day the optimal heart rate as well as the optimal point of the Starling curve in these patients was found at extremely low filling pressures Kirklin's scheme of therapy may be limited in these patients. Therefore, in low cardiac output syndrome, left ventricular filling pressure should only be increased after the optimal heart rate is selected by atrial stimulation.


An 11-year assessment of 93 flash-frozen homograft valves in the aortic position.

Flash-frozen homograft aortic valves were used for isolated aortic valve replacement at the National Heart Hospital between 1968 and 1971. This study of 93 patients with an average follow-up of 8.5 years complements a previous report on 30 patients but shows a higher incidence of degeneration. There was an early mortality of 4.8% and a late mortality of 15.9% over 11 years. Only five of the 15 late deaths were directly attributable to valve malfunction. There were no episodes of thromboembolism during the 11 year follow-up and only three cases of infective endocarditis. Despite the late onset of valve degeneration there is a 77% probability of patient survival at 11 years. The use of frozen valves delayed the time of onset of degenerative changes when compared over an 11-year period with the earlier use of freeze-dried valves. The evaluation of replacement cardiac valves is thus seen to be time-dependent and needs a long follow-up and an adequate number of patients in the sample for a meaningful assessment. There was no significant difference in the long-term performance between the frozen valves sterilized in ethylene oxide or sterilized with gamma irradiation.


Combined aortic and mitral valve replacement. A randomized study comparing the Björk-Shiley and Lillehei-Kaster disc valve.

The present series was comprised of 48 patients, 25 of whom received the Björk-Shiley (B-S) and 23 the Lillehei-Kaster (L-K) disc valves. The 2 groups were comparable with regard to age, and to preoperative clinical and hemodynamic status. The randomized selection was carried out at the beginning of the operation. The total mortality in the B-S and L-K groups was 16% and 21% respectively. All surviving patients were restudied 13-40 months (mean 27) after surgery. Late thromboembolic complications occurred in 2 patients with B-S and in 3 with L-K valves, all leaving minor neurological sequelae. There was a relatively large number of patients in the L-K group with unmeasurable values of haptoglobin, indicating more hemolysis in these patients. However, the difference was not statistically significant. The clinical and hemodynamic status was improved in both groups. In the aortic position a significant gradient was found across the L-K valve, while no significant obstruction in the flow was found in the B-S valve. The pulmonary arteriolar resistance was significantly higher in patients with B-S than in those with L-K valves. Otherwise, there was no significant differences between the 2 groups, neither with regard to clinical nor to hemodynamic status.


Fibrous tissue overgrowth on Hancock mitral xenografts: a cause of late prosthetic stenosis.

Severe prosthetic stenosis requiring reoperation seldom occurs after mitral valve replacement with the Hancock bioprosthesis. Two cases of prosthetic stenosis caused by tissue overgrowth on the atrial aspect of the cusps are reported. The patients, who had undergone mitral replacement with a Hancock valve implanted in the subannular position, developed the signs of congestive heart failure 5 and 6 years after surgery. In both patients, the hemodynamic data supported the clinical diagnosis of mitral restenosis and both underwent successful reoperation. Histologic examination showed that the pannus was formed by dense fibrous tissue with few vessels. It is suggested that the site of the bioprosthesis insertion is likely to have favored this complication since in this condition the protection of the sewing ring from tissue overgrowth is minimal.


Thrombembolic malfunction of a Björk-Shiley aortic valve prosthesis.

The case history and pathomorphological findings of a very rare fatal complication following prosthetic heart valve replacement are described: A 51-year-old woman died of acute malfunction of her Björk-Shiley aortic valve prosthesis caused by a large embolus deriving from the left atrium. After triple valve replacement 30 months earlier she seemed to be in good health. She had been subject to absolute arrhythmia for many years, and anticoagulation treatment had been felt to be sufficient.


Late changes in aorto-renal vein transplants.

The results of 152 renal artery reconstructions in 128 hypertensive patients were reviewed 1 to 15 years postoperatively in 89 of 98 survivors. Forty-seven (52.8%) patients were normotensive, 29 (32.6%) are improved, and 13 (14.6%) were not improved. Angiography was performed 1 to 11 years after the operation. Only 2 of the 31 vein implants showed an adequate lumen. Four vein grafts were occluded. In 2 out of 4 stenosed transplants stenosis was functionally significant, and the patients with recurrent hypertension underwent re-reconstruction. The causes of the stenoses were severe constriction by scar tissue and extensive subintimal cellular proliferation of the vein graft. Twelve of 31 vein bypass grafts were dilated by an average of 22%. The average increase in caliber of the remaining 9 vein grafts was 106%. The possible contributory factors were forceful distension, excessive adventitial dissection, inadequate storage of the vein, ischemic damage of the vein wall (especially in younger patients), and the increase flow rate through the transplant.


The HLA antigens and ABO blood groups in an American Black population with mitral valve prolapse.

A total of 42 American Black patients with mitral valve prolapse and 194 healthy individuals of similar ethnic background were tested for the distribution of various HLA antigens and ABO blood groups. The most significant result was an increased frequency of Bw35 in patients (74%) as compared with controls (39%), with a P value of less than 0.0001; the relative risk was 4.45.


Ultrastructure of sensory cells on the mantle tentacles of the gastropod Notoacmea scutum.

Previous studies have indicated that the mantle margin of the gastropod mollusc Notoacmea scutum is sensitive to chemical, photic, and mechanical stimulation. Here, the ultrastructure of sensory cells on the mantle tentacles of N. scutum is examined by transmission electron microscopy to determine if morphological types of sensory cells can be correlated with known sensory capabilities. The sensory cells of the mantle tentacles are found to be ciliated, primary receptors with subepithelial nuclei. The ciliated sensory endings are concentrated at the tip of the tentacles, but also occur in smaller numbers along the shaft. Ultrastructural differences between cilia form the basis of distinguishing two types of sensory ending. Type 1 sensory endings, which are over 90% of the endings, bar unusual cilia that typically are filled with an electron-dense material. Type 2 sensory endings bear cilia that have a 9 + 2 arrangement of longitudinal elements and thus more closely resemble previously reported sensory cilia of molluscs.


Morphological studies on the periostracum of the fresh-water mussel Amblema (Uniondae): light microscopy, transmission electron microscopy, and scanning electron microscopy.

The structure of the periostracum in the fresh-water mussel Amblema has been described using light microscopy, transmission elec;ron microscopy, and scanning electron microscopy. The structure and evolutive course of the periostracum was studied along its entire length, from the periostracal groove until it forms the tough outer covering of the shell. At least five structurally and functionally distinct regions were identified. In addition, the periostracum itself was seen to be a multilayered structure consisting of three major layers which are themselves subdivided into minor layers. From these morphological observations, a regulatory role for the various periostracal layers in mineral trapping, nucleation, and the subsequent formation of the prismatic and nacreous layers of the shell can be postulated.


Correlations between epidermal cell structure and endogenous hormone titers during the fifth larval instar of the tobacco hornworm, Manduca sexta.

Epidermal cell morphology and cuticle production in Manduca sexta are directly influenced by both ecdysterone and juvenile hormone. Up to day 6 of the last larval instar, post-molt endocuticle is continuously deposited even though cells undergo a partial and temporary separation from the overlying cuticle at the time when a small ecdysteroid peak is detected (approximately day 3.5). At about days 6--7 when another, larger ecdysteroid peak is present, apolysis occurs accompanied by the appearance of edcysial droplets. Following apolysis, layers of pupal cuticle are deposited. Increased quantities of rough endoplasmic reticulum characterize the epidermis at times of peak endocuticle deposition (day 3, larval cuticle; day 9, pupal cuticle). Dense pigment inclusions are found in epidermis from the day of ecdysis to the last larval instar until they are eliminated 5 days later. These dense bodies migrate from cell apex to base in the absence of juvenile hormone (or in the presence of a negligible amount of juvenile hormone) and probably contain insecticyanin.


Changes in fine structure of the ventral intersegmental abdominal muscles in the adult of Rhodnius prolixus.

In Rhodnius prolixus, after the imaginal molt, the intersegmental muscles completely lose their contractile material, and are transformed into thin strands containing nuclei. It is possible that these muscular strands are finally pinched off as mononucleated myoblasts. These residual muscles apparently maintain a normal innervation--which persists to the end of the imago's life. Moreover, they appear to show some aspects of synthetic activity after the adult has been fed: in this case, there is a growth of the 'rough endoplasmic reticulum' and elaboration of specialized fibrous inclusions.


The function of the follicular epithelium in vitellogenic Oncopeltus follicles.

Autoradiographic and electrophoretic methods that have detected an endogenously synthesized protein yolk component in Hyalophora cecropia follicles failed to reveal such a protein in Oncopeltus fasciatus. Similarly, neither sulfate nor glucosamine was incorporated into the intercellular matrix of vitellogenic follicles, though both label these regions intensely in Hyalophora. While both insects produce yolk from hemolymph vitellogenin, their follicles thus appear to support the process by very different synthetic means.


Gap junctions between Sertoli and germ cells of rat seminiferous tubules.

Ultrastructural observations of rat seminiferous tubules show clearly the presence of plasma membrane junctions between Sertoli and germ cells in the basal and adluminal compartments. Results obtained from the freeze fracture and thin section techniques were correlated in order to elucidate the nature of these intercellular junctions. We suggest that these intercellular membrane specializations are gap junctions which occur within regions of plasma membrane that also exhibit adherens-like modifications.


Morphology of the granular secretory glands in skin of poison-dart frogs (Dendrobatidae).

The granular glands of nine species of dendrobatid frogs were examined using light and electron microscopy. The glands are surrounded by a discontinuous layer of smooth muscle cells. Within the glands proper the secretory cells form a true syncytium. Multiple flattened nuclei lie at the periphery of the gland. The peripheral cytoplasm also contains mitochondria, rough surfaced endoplasmic reticulum, the Golgi apparatus, and an abundance of smooth endoplasmic reticulum. Centrally, most of the gland is filled with membrane-bound granules surrounded by amorphous cytoplasm. Few other organelles are found in this region. Early in the secretory cycle, the central part of the gland is filled with flocculent material which appears to be progressively partitioned off by membranes to form the droplet anlage. As granules form, the structure of the contents becomes progressively more vesicular. Dense vesicles, which bud off from the Golgi apparatus, fuse with the granular membrane during the development of granules, and might contain enzymes involved in toxin synthesis. The granules at this point resemble multivesicular bodies. Their structure is similar in all species of dendrobatid frogs even though the different frogs secrete substances of different chemical structure and toxicity.


Mammary gland development during pregnancy in the dwarf mouse mutant, little.

Little (lit) is a single gene dwarf mutation described in the C57Bl/6J strain of laboratory mouse. This study was designed to determine the effect of the mutation little on mammary gland development during pregnancy and post-partum periods. Failure of mutant females to lactate at first parturition appears to be due to the endocrine environment of the gland rather than any intrinsic defect of the mammary epithelium. Treatment of primiparous lit/lit females with exogenous growth hormone or prolactin resulted in lactogenesis. Treatment with hydrocortisone resulted in increased amounts of organized rough endoplasmic reticulum but lactation did not occur.


Gap and tight junctions in tunicates. Study in conventional and freeze-fracture techniques.

Intercellular junctions have been investigated in epidermis and pharyngeal epithelium of larvae and adults of various species of tunicates with conventional and freeze-fracture techniques. Gap and tight junctions were found, similar to those observed in vertebrate tissues. Gap junctions were frequent in glandular epithelia and in larval tissues. They were interpreted as ways of intercellular communication in these developing tissues. They were also particularly numerous in Phallusia pharyngeal cells. Tight junctions were found preferentially in adult pharyngeal and epidermal epithelia, where they were arranged in strands of distinct particles forming a belt-like network at the apical part of cells. These junctions were interpreted as providing a tight barrier between the internal medium and the external environment. In larvae, tight junctions were found only between epidermal cells of the tail. These junctions thus characterized completely differentiated tissues, where they might play, in tunicates and in vertebrates, the same role as septate junctions do in invertebrates.


The incorporation and distribution of 3H oleic acid in the isolated perfused guinea-pig heart: a biochemical and EM autoradiographic study.

The incorporation of 3H oleic acid into tissue lipids of guinea pig heart was studied after 15, 30, 60 or 120 sec perfusion using EM autoradiography with 'hypothetical grain' analysis and lipid analysis by thin-layer chromatography. Radioactivity in triacylglycerol and phospholipid increased and in free fatty acid decreased with time. This corresponded to an increase in radioactivity associated with lipid droplets in the autoradiographs. High levels of radioactivity were found associated with the mitochondria after only 15 sec. The movement of fatty acids is interpreted in terms of transport mechanisms, concentration gradients and bound and unbound molecules.


Programmed cell death. electrophysiological and ultrastructural correlations in metamorphosing muscles of lepidopteran insects.

Individual spontaneously degenerating fibers of moths have been examined successively by electrophysiological and ultrastructural techniques. The correlations observed by this method have revealed two phases of lysis. The first lytic phase begins at or before the ecdysis of the moth. It is characterized by a probable but occult respiratory lesion, normal movement of the ions across the plasma membrane, and limited degradation of myofilaments and autophagy of mitochondria. There are nevertheless early degenerative changes in the Z-band and a slight swelling of the T system. The second lytic phase is introduced, at approximately 15 hr after ecdysis, by collapse of the tracheal airways. The collapse of the tracheae is followed within 2 or 3 hr by a drastic reduction of input resistance, depolarization of the fiber, and loss of contractility. The rate of proteolysis increases, and the remaining myofilaments lose all structural identity by the twentieth hour. During this period of rapid change, the electron density of the reticular portion of the dyads decreases before a compactive process increases their opacity. Neural elements degenerate secondarily. The early lytic phases are apparently non-lysosomal for the myofilaments, although organelles such as mitochondria, ribosomes, and glycogen are destroyed in autophagic vacuoles. Elimination of oxygen and collapse of the resting potential, with the presumed equilibration of intracellular ionic content, provokes a rapid dissolution of the myofilament, with continued autophagic elimination of the organelles.


A method for micro-scale isolation of sulfated glycopeptide from tissue.

Micro-scale isolation of sulfated glycopeptide from tissue was achieved by successive application of pronase digestion (Step 1), cetylpyridinium chloride-fractionation (Step 2), crude heparinase digestion or chondroitinase ABC digestion plus nitrous acid treatment (Step 3) and preparative cellulose acetate membrane-electrophoresis (Step 4). By this method, sulfated glycopeptide was obtained in a high yield from estrogen-treated rabbit uterus.


Effect of triamterene on urinary excretion of immunoreactive prostaglandin E in essential hypertension.

The effect of triamterene on urinary excretion of prostaglandin E was studied, and the results were compared with those obtained with spironolactone. Urinary excretion of immunoreactive prostaglandin E was measured radioimmunologically. Triamterene was administered in a dose of 100 mg/day for 8 days to 7 patients with essential hypertension. Following the administration of triamterene, urinary prostaglandin E tended to increase. However, the increment was not significant. The lack of significant increase in urinary prostaglandin E excretion during the administration of triamterene contrasted with our previous finding with spironolactone, in which a significant increase in prostaglandin E excretion was observed on the first day of spironolactone administration. Urinary Na excretion and urinary Na/K ratio were significantly increased and urine volume also tended to increase following the administration of triamterene. Plasma renin activity and plasma aldosterone concentration were increased in all cases. However, there was no significant correlation between these parameters and urinary prostaglandin E. These results suggest that the effect of triamterene on renal prostaglandin E synthesis is different from that of spironolactone and that the change in urinary prostaglandin E after the administration of triamterene is not the reflection of the change in the renin-angiotensin-aldosterone system.


Experimental investigation on the pathogenesis of tartrazine-induced asthma.

The effects of tartrazine on the synthesis of prostaglandin-like substances (PGLS) from arachidonic acid in isolated perfused guinea pig lung, and on the contractile responses of guinea pig tracheal tissues induced by histamine, acetylcholine, bradykinin, serotonin and prostaglandin F2 alpha were studied. The synthesis of PGLS from arachidonic acid was not inhibited by tartrazine. The contractile responses of guinea pig tracheal tissues induced by various bronchoconstrictors were potentiated in the presence of tartrazine. These results may suggest that tartrazine-induced asthma is not induced by inhibition of PGLS synthesis, but induced by potentiation of bronchoconstrictor responses.


Cytological diagnosis in dysplasia of the uterine cervix.

Cytologic specimens presenting primarily superficial or intermediate dysplastic cells in the smear obtained by scraping the uterine cervix were defined as mild dysplasia, and those presenting primarily parabasal (or deep layer) dysplastic cells were defined as severe dysplasia. The rate of agreement of the above cytologic diagnosis to the histological diagnosis by target biopsy using the colposcope was 50% and 51% in mild and severe dysplasia, respectively. Specimens containing a few atypical cells which were strongly suspected to be malignant were classified as IIIb. From this group, malignant lesions were found in 48% and severe dysplasia in 35%.


PaCO2 for optimum washout of inhalational anesthetics from the brain. A model study.

A hypothesis was established that, during emergence of inhalational anesthesia, hyperventilation and accompanying hypocapnia beyond a certain limit may actually disturb rather than enhance the washout of inhalational anesthetics from the brain because of a decreased cerebral blood flow. Two mathematical models were constructed and the washout of nitrous oxide, halothane and methoxyflurane were studied. In model I, the whole body consisted of a single compartment, and blood flow to this compartment was assumed to change proprotionally with the PaCO2. In model 2, the body was divided into two compartments, brain and the rest of the body. It was assumed that the blood flow to the brain compartment varies proportionally with the PaCO2, while that to the rest of the body remains constant. The analysis indicated that there indeed existed the PaCO2 values at which the washout of anesthetics from the brain can be maximally achieved. In model 1, they were 49.0, 22.1 and 9.7 mmHg for nitrous oxide, halothane, and methoxyflurane, respectively. In model 2, these PaCO2 values varied with time. While the hypothesis was proven to be valid, we conclude that it is of limited clinical significance. For halothane and methoxyflurane, these theoretically optimum PaCO2 values are sufficiently low. For nitrous oxide, the variation of PaCO2 makes little difference clinically, because its washout is fast enough regardless of PaCO2.


The normal levels of fluorine in the bone tissue of Japanese subjects.

The variation of fluorine concentration by sex and age in bones of Japanese subjects was estimated. The subjects had lived in districts virtually with no fluoride in drinking water and air. The rib bone and the iliac crest were selected for investigation. The fluorine concentration in bones was about 100 ppm in dry (fat-free) weight and 200-230 ppm in ash weight from birth to 19 in both sexes, and increased in their twenties, reaching a plateau level in the 60's. The fluorine concentration in rib bones, however, was 610 ppm in dry (fat-free) weight and 1100 ppm in ash weight, which was slightly higher than that in ilia with 530 ppm in dry (fat-free) weight and 960 ppm in ash weight, respectively. The bones of males contained more fluorine than those of females. The concentration of Ca, P and Mg in bone tissue did not correlate with fluorine concentration.


Multidrug combination in cancer chemotherapy: MFU therapy.

Three-drug therapy with Mitomycin-C (MMC), 5-fluorouracil (5-FU), and a nitrosourea derivative, ACNU, was carried out in 72 cases of carcinoma patients, mostly of stomach carcinoma. 1) According to Karnofsky's criteria, an effect of above I-A was observed in 10 of 35 cases (29%) treated with MFU-I (0.08 mg/kg of MMC, 10 mg/kg of 5-FU and 0.4-0.8 mg/kg of ACNU twice a week for the first two weeks and once a week thereafter for a total of six weeks as one course), 5 of 14 cases (36%) with MFU-I-O (MFU-I plus 0.2-2.0 KE of OK-432 i.m. three times a week), and 6 of 20 cases (30%) with MFU-II (0.2 mg/kg of MMC once in two weeks, 5 mg/kg of 5-FU every day, 2 mg/kg of ACNU once in six weeks as one course). 2) According to the criteria of the group of Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, a partial response was seen in 29% of the cases treated with MFU-I, in 38% of the cases treated with MFU-I-O, and 30% of the cases treated with MFU-II. 3) Side effect was slight in the digestive organs but the bone marrow suppression was remarkable. Leukopenia and thrombocytopenia were seen in the majority of patients under treatment. The hematological side effect appeared early in MFU-II therapy, but it was not severe and recovered quickly. Combined use of OK-432 seemed to be effective to shorten the period of hematological disorders. Thus, three-drug combination treatment with MMC, 5-FU, and ACNU seems to be useful for patients with malignant tumor, chiefly of the digestive organs. Especially, MFU-II treatment schedule seems to be a combination therapy that has relatively small hematological side effects.


Mitogenic effect of a novel animal lectin on human lymphocytes.

The mitogenic effect of the novel lectin prepared from an animal source on human lymphocytes was examined in comparison with that of phytohemagglutinin-p (PHA-p) by the uptake of 3H-thymidine. The uptake of 3H-thymidine by lymphoblasts was enhanced by the treatment with the lectin as well as with PHA-p, though the effect of the lectin was difficult to compare exactly with that of PHA-p.


Alcoholic liver disease in women.

In 1972-1977, 130 patients with alcoholic liver disease (123 men and 7 women) were admitted. A half of the women had occupations which are related with alcohol consumption and a half were housewives. Daily consumption of alcohol in the women was the same as in the men. Duration of excessive drinking was 11.4 years in the women and 17.1 years in the men, but the difference was not statistically significant. Though the difference of the incidence of alcoholic hepatitis in the women (57%) and in the men (27%) was not statistically significant, frequency of ascites was significantly higher in the women (43%) than in the men (7%). Women seem to be more susceptible to severe form of alcoholic liver damage.


Ultrastructural pathology of peripheral nerves in patients with diabetic neuropathy.

Sural nerve lesions in patients with clinically manifest diabetic neuropathy were investigated electron microscopically. Myelinated nerve fibers were reduced in all the diabetic patients. Axonal degeneration of both myelinated and unmyelinated nerve fibers was most conspicuous finding in the diabetic sural nerves. Structural changes of the axons were represented by axonal dwindling, depletion of axoplasmic organelles, vacuolarization and an increase in neurofilaments. Accumulation of glycogen-like particles and deposition of electron homogeneous amorphous materials were noted within a few axons. On the other hand, there could also be found degenerative changes of myelin sheaths, various kinds of cytoplasmic inclusion bodies (crystalloid, lamellar inclusion bodies and lipids-like droplets), aggregates of glycogen particles in the Schwann cell cytoplasm and basement membrane hyperplasia of Schwann cells in all the subjects. Furthermore, multiplication and thickening of the basement membrane of vasa nervorum were constant findings of the diabetic sural nerves. The vascular changes, demyelination and axonal degeneration of the cases were not apparently correlated with each other. There was no special relationship between nerve tissue changes and clinical symptoms or laboratory findings. These results indicated that the peripheral nerve lesions in human diabetics were mainly due to metabolic impairment of nerve fibers, accompanying dysmetabolism of Schwann cells and diabetic microangiopathy, and that these changes proceeded independently.


A scanning electron microscopic study on the liver of mice.

The three-dimensional fine structures of several tissue components of the liver in normal mice were studied by scanning electron microscopy. The tissue components observed were as follows: hepatocytes, sinusoidal endothelial cells, the Kupffer cells, fat-storing cells, reticulin fibers and epithelial cells of the bile duct. Two types of fenestrations were found in the sinusoidal endothelial cells. One was smaller and clustered, and the other larger and scattered. Both of them were distributed equally throughout the hepatic lobule. Intercellular gaps were found at the endothelial junction. The Kupffer cell which was localized in a large gap between the endothelial cells was characterized by numerous villous projections, and by the absence of fenestrations which were observed in the endothelial cells. Fat-storing cells were located between hepatocytes. They elongated their processes into the space of Disse, but never protruded into the sinusoidal lumen. They were clearly distinguished from the endothelial cells and the Kupffer cells by their morphological feature and location. No transitional form was seen among the endothelial cells, the Kupffer cells, and the fat-storing cells.


The effect of a single sublethal administration of cadmium chloride on the microcirculation in the uterus of the rat.

A light microscopical and ultrastructural survey of the early effects of cadmium chloride in the uterus of the prepubertal rat was performed. 3 h after injection of CdCl2 evidence of injury to the microcirculation was ultrastructurally apparent. The phenomena consisted of nuclear and nucleolar changes, extensive pinocytotic activity, vacuolisation of the cytoplasmic matrix, distension of the cisternae of the endoplasmic reticulum and an increase in cytoplasmic protrusions in the lumen of the cell. After 6 h the damage had increased and a certain portion of the endothelial cells showed signs of degeneration. At 24 h the changes were maximal and extruded red cells were observed in the interstitial tissue by light microscopy. At 48 h recovery had started and the situation appeared to return to normal.


Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the hepatic metabolism of testosterone in the rat.

A dose of 20 micrograms/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was given to adult male rats intragastrically and the metabolism of [4-14C]-testosterone by liver homogenate was examined 1 week later. The overall catabolism of testosterone was significantly reduced by the TCDD treatment. Dihydroxysteroids (intermediate reduced metabolites) were increased, while the production of polar non-conjugated metabolites (end products) was diminished.


Canine pituitary-testicular function in relation to toxicity testing.

The physiological onset and establishment of adult pituitary-testicular function has been characterised for Beagle dogs. Testicular measurements, circulating prolactin, luteinising hormone and testosterone concentrations, semen analyses and the histological appearance of testicular biopsies, suggest that male Beagles attain sexual maturity between 35 and 41 weeks of age. The assessment of testicular toxicity is discussed and attention drawn to possible approaches for investigating primary mechanisms of toxic action on the canine testis. Expected values for testicular size, hormone levels and semen characteristics are reported.


Effects of lead microparticles on the growth characteristics of the BHK21 fibroblast cell line.

BHK21 fibroblastic cells were exposed in vitro to lead microparticles produced by pyrolysis of the organic lead used as an antiknock agent in gasoline. Although non-cytolethal, 10 micrograms of lead/10(6) cells rapidly inhibited cell growth kinetics as well as [3H]thymidine and L-[3H]leucine incorporation by the BHK21 cell line. The growth rate inhibition provoked by chronic exposure to lead microparticles became reversible when the cells were cultured without the microparticulate pollutant. The cloning efficiency of BHK21 cells was impaired by lead concentrations above 1 mg/10(6) cells.


Micro-buffy coats of whole blood: a method for the electron microscopic study of mononuclear cells.

A method for the electron microscopic study of human peripheral lymphocytes by which very small buffy coats are obtained through centrifugation of heparinized whole blood in glass or plastic microhematocrit tubes is presented. This method is time saving and efficient, yielding well preserved material and a comparatively large number of mononuclear cells (mainly lymphocytes) in each thin section.


Ischemic cerebral edema. A review.

The genesis of ischemic cerebral edema is multi-factorial and the relative importance of these many factors varies throughout the lesion and with time. The initial event is intracellular edema which may be followed by extracellular edema. This situation precludes any simple treatment, particularly because the favorable alteration of one factor might be detrimental to another.


Attenuation of ischemic brain edema by pentobarbital after carotid ligation in the gerbil.

The efficacy of pentobarbital in the treatment of ischemic cerebral edema was evaluated in 160 gerbils. Animals underwent carotid ligation under ether or pentobarbital (50 mg/kg) anesthesia. The pentobarbital anesthetized group received an additional dose of 30 mg/kg 4 h after ligation. Animals were evaluated for neurologic deficit at 4 and 8 h post-ligation, then sacrificed. Water content of each hemisphere and swelling percentage were calculated from the wet and dry weights of the hemispheres. Swelling percentage in animals anesthetized with ether was 6.374 +/- 0.89 SE, whereas gerbils who underwent sham carotid ligation showed a negligible (0.491 +/- 0.15) swelling percentage (p less than 0.01). Pentobarbital animals had a swelling percentage of 3.359 +/- 0.68. This represents a significant edema reduction compared to ether-anesthetized animals (p less than 0.01). Neurologic deficit was decreased by 56.7% (17/60 vs 30/60) in pentobarbital animals compared with ether animals (p less than 0.025). Mortality at 8 hours was reduced by 75% (2/60 vs 8/60) in pentobarbital animals (p less than 0.05).


Influence of various agents on the development of brain edema in the rat following microembolism. Protective effect of gamma-butyrolactone.

Brain edema was induced in rats by injecting 50 mu microspheres, labelled with 85Sr, into the internal carotid artery. The use of radioactive microspheres as embolic agents enabled the number of microspheres to be determined in each cerebral hemisphere. Edema was assessed 12 or 24 h after embolization by measuring brain water content and, in some experiments, sodium and potassium. Pretreatments with dexamethasone, parachlorophenylalanine (an inhibitor of 5-hydroxytryptamine synthesis), mepyramine and metiamide (H1 and H2 histamine receptor antagonists) or aminophylline did not influence significantly the development of brain edema evaluated 24 h after embolization. Aminophylline treatment (100 mg/kg) markedly increased mortality following embolization. Gamma-butyrolactone (300 mg/kg, every 2 h) inhibited significantly the development of brain edema evaluated 12 hours after embolization. Increases in water and sodium in the embolized cerebral hemisphere were reduced by about 50%. This protective effect may be related to the known depressant action on brain metabolism.


Changing pattern of cerebral infarction: 1945--1974.

This study has identified all persons in the population of Rochester, Minnesota, who had a diagnosis of cerebral infarction during the period Jan. 1, 1970, through Dec. 31, 1974, and has confirmed the continuing decline in the incidence rate previously reported. The decline in the rate has been accelerating, with a relatively greater reduction occurring in women and in the more elderly age groups. There has been a decline in the prevalence rate in women which was not seen in men. The over-all impact of cerebral infarction was to reduce the proportion of those persons who were completely independent from 57% before cerebral infarction to 16% after infarction. Comparison of survival among patients with cerebral infarction occurring in the two quinquennia 1945--49 and 1970--74 showed only a 2% increased probability of survival at 30 days; the difference in survival increased progressively to 16% at 5 years. The reason for the declining incidence and increased survival in cerebral infarction in this population has not been established, but evidence of increased community surveillance and treatment of hypertension among persons before the onset of cerebral infarction is presented.


Recovery in treated aphasia in the first year post-stroke.

During a one year post-stroke period of observation, the recovery trend in treated aphasic patients was characterized by general progression in communication skill. The most notable improvement occurred on a measure of everyday function with changes worthy of note on tasks of auditory comprehension and spontaneous word production. In the first 6 months post-stroke, the greatest gain occurred in aphasic patients classified as Fluent, and the least gain in Global aphasics. On the auditory comprehension task, however, improvement was noted in all aphasics regardless of type. In contrast, during the latter half of the first year post-stroke, Fluent aphasics showed least and Global aphasics the greatest improvement. In spite of their progress, Global aphasic patients remained considerably more impaired than the other groups. That the Global aphasics remained so impaired was expected, but the extent and temporal characteristics of their progress in communicating was unexpected.


Intracranial venous thrombosis in young women.

Twenty women of child-bearing age with intracranial venous thrombosis are reported. Thirteen developed thrombosis post-partum; 6 while on oral contraceptives. In one patient no cause was found. All diagnoses were confirmed by carotid angiography and in 10 out of 14 patients laboratory data indicated a hypercoagulable state. Coagulation studies were performed in 14 normal puerperal women, matched by age, who served as controls. No statistical differences was found between thrombotic and control groups. Radiologic signs of sino-venous occlusion are reviewed. Conservative treatment with anti-edematous agents, anticonvulsants and antiplatelet aggregants is advocated.


Histopathological reactivity of carotid arteries of normotensive Sprague-Dawley vs spontaneously hypertensive rats to ligation injury.

The common carotid arteries of normotensive non-arteriosclerotic Sprague-Dawley (S-D) rats, mildly hypertensive but arteriosclerotic breeder S-D rats, severely hypertensive but non-arteriosclerotic virgin spontaneously hypertensive rats (SHR), and severely hypertensive breeder SHR were ligated to induce injury. Three weeks post-ligation, the animals were killed and histopathological sections of the ligated artery demonstrated myointimal proliferation without occlusion in the normotensive S-D rats but myointimal proliferation with occlusion in the severely hypertensive SHR. Breeder S-D rats with moderate hypertension manifested a high incidence of total occlusion by combined myointimal proliferation and thrombosis. Severely hypertensive breeder SHR manifested a high incidence of massive thrombi containing cholesterol clefts causing total occlusion of the injured artery. It is suggested that the severity of the hypertension and the hormonal-metabolic milieu conditions the morphologic response of the arterial wall to injury.


Levels in stroke patients of CSF astroprotein, an astrocyte-specific cerebroprotein.

Astroprotein (an astrocyte-specific cerebroprotein) levels in cerebrospinal fluid (CSF) were determined by radioimmunoassay in 47 stroke patients. (Astroprotein is immunologically identical to glial fibrillary acidic protein.) Astroprotein levels in CSF increased markedly in acute cases of intracerebral hemorrhage and slightly to moderately in some acute cases of subarachnoid hemorrhage and cerebral infarction. In intracerebral hemorrhage, CSF astroprotein levels in the acute stage of the ictus reflected the size of the lesion and were used to estimate the clinical outcome. In subarachnoid hemorrhage and cerebral infarction, CSF astroprotein levels were related to the general neurological state. Evidence obtained indicated that fundamentally different destructive and/or degenerative processes in the brain may be involved in intracerebral hemorrhage, subarachnoid hemorrhage and cerebral infarction and that determination of CSF astroprotein may have clinical significance in stroke patients.


Measurement of regional brain glucose utilization in vivo using [2(-14)C] glucose.

A new technique is described for the autoradiographic determination of regional brain glucose metabolism employing 14C labeled glucose as substrate and measurement principles previously described for whole brain. Regional glucose values correlate closely with those reported for the 14C-deoxyglucose technique. The method has the advantages of 1) a much shorter experimental period, 2) a relatively simple mathematical treatment, and 3) the utilization of the actual, fully metabolizable substance itself, glucose, as the label. In addition to normal rats, regional values are reported for 20 individual brain areas of rats in bicuculline induced status epilepticus, rats intoxicated with ammonium and rats anesthetized with pentobarbital sodium or ketamine.


Experimental cerebral vasospasm after subarachnoid hemorrhage. Participation of adrenergic nerves in cerebral vessel wall.

Distribution and morphology of nerves in basilar-artery-induced vasospasm were investigated electronmicroscopically. Small cored vesicles were transformed, decreased and disappeared gradually after development of vasospasm induced by blood-CSF mixture incubated 5--10 days. These changes were not induced by fresh arterial blood, lysed platelets in saline and mechanical stimulation. In the portion with severe vasospasm induced by incubated blood-CSF mixture, nerve distribution was rich and uniform in all portions of the adventitia. In the portion with slight vasospasm, nerves were extremely scanty in the innermost area of the adventitia, within 10 mu from the outer edge of the media. The severity of experimental vasospasm became definitely lighter and the duration shorter after bilateral cervical sympathectomy. These findings indicate that nerves, especially the adrenergic axon in the innermost area of the adventitia, may play an important role on the genesis of late vasospasm. The difference in nerve distribution may be a factor influencing individual differences in frequency or severity of vasospasm.


Effects of hemorrhagic hypotension on the cerebral circulation. II. Electrocortical function.

The effects of graded hemorrhagic hypotension on electrocortical function was investigated in 12 cats anesthetized with alpha-chloralose. Cerebral function was assessed both in terms of spontaneous activity (EEG) and the somatosensory evoked response. No significant changes in the EEG trace or in the amplitude of the positive/negative waves of the primary evoked response were observed at mean arterial pressures of between 120 mm Hg and 40 mm Hg. At levels of systemic arterial pressure of less than 40 mm Hg cortical rhythms became slower as pressure was decreased and an isoelectric EEG was recorded in the pressure range 10--30 mm Hg. The earliest sign of any change in the amplitude of the primary evoked responses was observed at arterial pressures of approximately 35--40 mm Hg. Below this value the amplitude decreased with decreasing systemic pressure and became zero in the pressure range 15--25 mm Hg.


Correlated electrical and mechanical responses of isolated rabbit pial arteries to some vasoactive drugs.

Simultaneous measurements were made of spike activity and perfusion pressure (PA) in intact segments of rabbit middle cerebral artery in vitro. The segments were mounted on a Teflon tube designed so that the perfusing solution flowed in the annular space between the tube and the artery wall, thus magnifying the PA changes occurring when the artery constricted or dilated. A widened portion of the Teflon tube immobilized 1--2 mm of the artery segment for electrical recording with fine glass microelectrodes. Spontaneous spike activity (extra- and intracellular) was regularly observed. When a steady PA and spike discharge was obtained, tests were performed by substituting for the normal perfusion liquid, solutions containing 5 microgram/ml norepinephrine, 5 microgram/ml angiotensin II or 7.5 microgram/ml isoproterenol. Norepinephrine and angiotensin each increased spike frequency (+ 293 and + 126%) and PA (+ 6.6 and + 7.9 mm Hg) whereas isoproterenol decreased spike frequency (-89%) and PA (-22.9 mm Hg). These results a) confirm the presence of receptors to these agents in pial arteries, and b) demonstrate a high degree of correlation between membrane electrical events and mechanical activity of these spontaneously-active myovascular cells.


Effects of hemorrhagic hypotension on the cerebral circulation. III. Neuropathology.

A neuropathological examination was made of 15 cats anesthetized with alpha-chloralose, subjected to a stepwise reduction in mean arterial pressure by graded hemorrhagic hypotension. Five animals were sacrificed by perfusion-fixation at a mean arterial pressure of 75 mm Hg, 5 at a mean pressure of 35 mm Hg and 5 at 25 mm Hg. Ischemic brain damage was seen in only 5 animals, one sacrificed at a mean arterial pressure of 35 mm Hg and 4 at a pressure of 25 mm Hg. It was maximal in the selectively vulnerable areas and included the boundary zones between the major arteries of the cerebral hemispheres, the Ammon's horn and the thalamus.


Ultrastructure of human platelets processed for transfusion under standard blood bank conditions.

Platelets processed for transfusion are routinely subjected to centrifugation, mechanical agitation and storage at either room temperature or 4 C. To evaluate morphologic changes associated with standard blood bank conditions, platelet units were grouped into four categories: linear agitation at room temperature, agitation at a 90 degrees arc with a Hemolater at room temperature, agitation at a 360 degrees arc with a commercial platelet agitator, and refirgeration at 4 C without agitation. Cold (4 C) preservation resulted in a surprisingly good preservation of platelet ultrastructure, even at 72 hours of storage. By contrast, harsh linear agitation at room temperature brought about marked alterations in platelet ultrastructure beginning at 24 hours. The Hemolator agitator with 90 degrees arc was associated with good preservation of platelet organelles even at 72 hours, whereas marked degenerative changes were observed at this time in platelets processed with a commercial agitator with a 360 degrees arc. These results indicate that platelets stored at 4 C or processed at room temperature with an agitator with 90 degrees arc show the best preservation of ultrastructure.


Weekly rotation of blood inventory--a system for supplying small hospitals.

A system of weekly turnover of blood inventory has been shown capable of reducing outdating in small hospitals. One problem is ensuring the return of unused blood at the end of the first week. Outdating becomes intolerable if the blood is returned to the blood center after two weeks.


Human granulocyte isolation by continuous flow centrifugation leukapheresis and counterflow centrifugation elutriation (CFCL/CCE).

Human granulocytes (PMNL) isolated by continuous flow centrifugation leukapheresis (CFCL) were further purified by counterflow centrifugation elutriation (CCE). Studies were conducted to determine the maximal granulocyte capacity of the 4.5-ml elutriation chamber and to determine the efficiency of granulocyte recovery from CFCL concentrates. The maximal capacity of the elutriation chamber was determined to be 1.30 x 10(9) granulocytes with a 98.8 percent granulocyte purity and a 51:1 PMNL/RBC ratio. The efficiency of recovery was 82.2 percent with a 95.1 percent granulocyte purity and a 68:1 PMNL/RBC ratio. The CCE flow system was designed to allow continuous elutriation runs without need of breakdown time between runs. In four to five hours, approximately 4 to 5 x 10(9) granulocytes can be isolated with purity in excess of 95 percent. In vitro analysis of the viability and function of CFCL/CCE-isolated granulocytes indicates that the morphologic integrity and physiologic function were not comprised as a result of the combined isolation procedure relative to granulocytes isolated by CCE from whole blood samples. Granulocytes were held at 4 to 6 C for 16 to 24 hours in granulocyte storage medium (GSM) plus 20 percent autologous plasma at concentrations of about 6 x 10(6) PMNL/ml prior to in vitro analysis.


The relationship of granulocyte ATP to chemotactic response during storage.

During the storage of granulocytes, bactericidal activity declines more slowly than does chemotactic response (CTR). Bacterial killing involves increased activity of the hexose monophosphate shunt, oxygen utilization and the generation of toxic products of oxygen. Chemotaxis is probably a contractile process involving myosin and actin filaments and possibly ATP as a source of energy. Thus, maintainance of ATP may be important in granulocyte preservation. During storage at 1 to 6 C of granulocytes collected by continuous and intermittent flow centrifuge leukapheresis, both CTR and ATP decreased approximately 33 percent. Decreases in CTR and ATP were 12 and 10 percent respectively when cells were stored at 20 to 24 C. Further decreases in CTR and ATP occurred between 24 and 48 hours of storage, although levels of both were higher in cells stored at 20 to 24 C compared with those stored at 1 to 6 C. When the results from all storage conditions were combined, the overall coefficient of correlation between CTR and ATP was 0.71 (p less than .05). Although ATP is probably not the only important variable in granulocyte preservation, granulocytes may resemble red blood cells in that a minimal level of ATP may be necessary for adequate function.


II. Operational experiments in the outpatient department (1970-1972).

Many of the recommendations, resulting from the previous study, to improve efficiency and to reduce waiting time and queueing, were put into practice in 1970 and evaluated in 1972. Most changes turned out to be improvements by all indicators, but some were not and several resulted in unforeseen sideeffects. Moreover the modified system proved to be vulnerable as it required rigorous coordination, greater motivation and stricter discipline among staff as well some extra material inputs.


The use of purified lectins in immunhematology.

A simple method for preparing purified lectins for use in immunohematology, employing bovine albumin as a diluent, is described. The results of tests using purified lectins on normal, polyagglutinable and selected MN-system variant red blood cells, confirm and extend previously reported results obtained with impure lectin preparations.


A comparison of six procedures for compatibility testing.

Six procedures for compatibility testing were compared, using red blood cells sensitized in normal saline, albumin or low-ionic strength saline (LISS) combined with either broad spectrum or anti-IgG antiglobulin testing (AGT). Despite shortened incubation times, tests employing LISS were as sensitive as those with albumin and broad spectrum AGT and more sensitive than the other four combinations. No false positive results were found. LISS technique with broad spectrum AGT appears to be suitable and superior for routine antibody detection and compatibility tests.


A comparison of platelets prepared by the Haemonetics Model 30 and multiunit bag plateletpheresis.

Platelet concentrates were prepared using the Haemonetics Model 30 (M-30) and a multiunit bag pheresis method. Comparisons of collection efficiency using paired donor collections and posttransfusion recovery using the same donor-recipient pairs were made for the two methods. The M-30 proved consistently superior as a method of collection in terms of efficiency and yield per hour (p less than .001). When the platelets obtained were transfused to HL-A matched, clinically stable, thrombocytopenic patients with acute leukemia similar increments within the expected range were obtained at 1 hour and 18 hours posttransfusion. While the M-30 is a more efficient collection method, the bag method is still relatively efficient and may be more suitable for smaller centers and specialized uses.


Screen filtration pressure and quantity of microaggregates: a nonexisting relationship.

In 22 units of stored canine blood, the relationships between screen filtration pressure and number and volumes of microaggregates were studied. No correlations were found. As high screen filtration pressure in transfused blood has been associated with organ dysfunction, its measurement may have some clinical merit.


III. Profile, expectation and satisfaction of outpatients (1970-1972).

The present study deals with patients' assessment of the OPD and the experimental changes in terms of "patient satisfaction". The hypothesis tested, stated that the level of satisfaction of clients of the OPD at Machakos hospital would increase after the introduction of changes in the operational and technical procedures. Data on clients' profiles and satisfaction were collected by means of structured interview schedule; 24 background variables and 17 satisfaction indicators were selected for final analysis to compare profiles and satisfaction of 324 baseline and 367 evaluation respondents. Profiles and satisfaction differed significantly at the 5% level. The significant difference in satisfaction could not be explained by the difference in profiles; the hypothesis was confirmed. A detailed analysis showed that total clinic time (the total time patients spent in the clinic) was significantly correlated with some of the 24 background variables and with some of the 17 satisfaction indicators; its duration was one of the key determinants for patient satisfaction, with a highly discriminative value. Another key variable was the answer to the question: "Did you get the treatment you wanted?". OPD patients discriminated various aspects and facets of OPD process and procedures for their assessment.


Stability of solutions of human granulocyte lactate dehydrogenase stored at different temperatures.

Granulocyte suspensions from eight healthy individuals were lysed ultrasonically in 0.15 M NaCl or serum. The leukolysates were tested for lactate dehydrogenase after being stored at 22 C, 5 C, -20 C and -196 C for one, two, three, four and seven days. The LDH content of granulocytes was 291 IU/10(10) cells (mean) and the enzyme had a characteristic isoenzyme pattern rich in LDH-5 with stepwise increases in each fraction from LDH-1 to LDH-5. The enzyme was unstable in saline solutions. This was marked at -20 C and related to the duration of storage. All the isoenzyme fractions showed significant inactivation. A mean 10% loss of activity occurred at -196 C. This loss was independent of the duration of storage and related to the process of freezing and thawing. Moderate inactivation occurred at room temperature while refrigerated samples were stable for four days. Serum protected the enzyme from denaturation and samples stored at -20, -196 and 22 C were stable for the seven days of the experiment.


I. An operational study in the outpatient department of Machakos Hospital (1968).

The demand for outpatient services at Government Hospitals in Kenya increased considerably during the period 1962-1967. As a result a discrepancy developed between demand for services and the resources to meet these demands. An operational study, dealing with medical, technical and administrative aspects, was carried out at the outpatient department at Machakos Hospital in 1968. The study comprised: the arrival pattern of patients, work measurement of the activities of the medical assistant, diagnosis, prescriptions, the distribution of patients over the therapeutic units, waiting times and length of queues. Following the study recommendations, expected to improve the efficiency of the clinic and the service to the patients, were put forward to the Ministry of Health. The most important recommendations dealt with: the need for overall leadership; direction of traffic; the position and the role of the medical assistant; the organization procedures, in particular at the medical assistants' units and at the injection room and pharmacy. The present study does not include: the attitude of the staff; expectation and satisfaction of patients; the quality of care provided; the cost of service.


IV. Health services research; the case of the outpatient department.

The main findings of the series of operational and satisfaction studies in the outpatient department of Machakos Hospital (1968-1972) were presented as a case study of evaluation research. The relevant theoretical aspects of evaluation research in the ambulatory care setting are reviewed. In an attempt to feed back the implications of the above studies for planning and management of services, for training of staff and for future research are presented.


Vernal eye disease in Northern Nigeria.

An analysis of 108 cases of vernal eye disease observed in Northern Nigeria. Although the bulbar and tarsal forms usually coexisted, the disease was predominantly bulbar in young children and predominantly palpebral in older patients. Chacteristic pigmentary conjunctival changes were particularly marked in young children. Corneal involvement occurred mostly in those patients with the palpebral form of the disease. The risk of permanent visual impairment in untreated cases appears to be slight.


The clinical and radiological evaluation of neonatal necrotising enterocolitis in Benin City, Nigeria.

Twenty four cases of neonatal necrotising enterocolitis seen at the University of Benin Teaching Hospital over a two year period are analysed. The clinical features of this entity were characterised by abdominal distension, apnoeic attacks, refusal to feed, bloody diarrhoea and fever. Seventeen infants (71%) were preterm. The important radiologic findings on plain abdominal films were pneumatosis intestinalis, pneumoperitoneum, abdominal distension and gas in the portal venous system. Twenty two of the 24 infants were treated conservatively. There was an overall mortality of 75%. The main pathologic findings were coagulation necrosis, mucosal ulceration and pneumatosis intestinalis. The roles of asphyxia, umbilical venous catherisation and septicaemia are stressed.


Tropical splenomegaly syndrome or chronic lymphatic leukaemia?

Four patients with the Tropical Splenomegaly Syndrome, showing marked lymphoid hyperplasia were studied, using immunological techniques. It has not been possible to decide on a definite diagnosis; chronic lymphatic leukaemia could not be excluded. Careful follow-up of similar patients may provide important clues to the pathogenesis of these diseases.


Gastric ulcer in Zaria, Nigeria.

In 1971 to 1977, 34 patients were operated for gastric ulcer at Zaria in the Savannah region of Northern Nigeria. The most frequent operation (35%) was for perforation. The frequency of perforation is similar to Ibadan's but smaller than Dakar's. Compared with Ibadan and Burundi, there are fewer women, more Type I ulcers and more frequent haemorrhages. There were three giant lesser curvature ulcers. Only a few combined duodenal and gastric ulcers were seen suggesting that gastric stasis is not the immediate factor in the production of gastric ulcer in this region.


Mortality in middle-aged Nigerians: an autopsy study.

Analysis of a 5-year autopsy data on Nigerians aged 31--60 years showed infective, cardiac and neoplastic diseases as major causes of mortality in these age groups. Improvement in public health and socio-economic circumstances, and preservation of cultural dietary habits would prevent a large proportion of deaths and a rise in degenerative diseases.


Body bulid and nutritional status of three ethnic groups inhabiting the same locality in Northern Nigeria.

Main objective of this study is to determine variables related to body build and blood status of three different ethnic groups inhabiting the same locality in Northern Nigeria. Of a stratified sample of the adult male population of a village community anthropometric measurements were taken. Body build of full grown men of each of the local Fulani, Hausa and Maguzawa tribes was recorded. This included height, weight, total and muscle arm-circumference, triceps and biceps skinfolds and the determination of the Quetelet and Ponderal indices. Fulani have the same stature as Hausa and Maguzawa but they have a more linear body type, less body mass, a lesser triceps skinfold, a lower Quetelet but a higher Ponderal index. The caloric intake of the local population is considered marginally sufficient, especially for Fulani, who may have a higher energy expenditure. Malaria and Schistosoma haematobium infections are highly endemic in the area and deteriorate the nutritional state. This is more evident in Hausa and Maguzawa than in Fulani, as is a degree of anaemia probably due to iron deficiency. In the Fulani the interaction of diet and infection appears to be more complex.


A new leptospiral serovar in The pyrogenes serogroup.

A new leptospiral serovar in the Pyrogenes serogroup is described. Parallel investigations by the 'classical' cross-agglutinin absorption test method and the 'factor analysis' method determined the serological properties of the new serovar. The serovar name kwale with reference strain Julu is proposed.


Pharmacological effects of the giant African snail Achatina fulica.

The body fluid and tissue extract of the foot of Achatina fulica, the edible giant African snail, were investigated and quantified for pharmacological effects. Both reduced spontaneous locomotor activity in mice, protected them from death from amphetamine induced toxicity, prolonged hexobarbitone sleeping time and caused a depletion of catecholamines from various organs of the rat. From this a central depressant action combined with an antihypertensive effect is inferred. This is in keeping with the objectives of local traditional healers who use the snail on their patients. It is suggested that eledoison, a potent antihypotensive agent found in aquatic snails may also be present in terrestrial snails such as Achatina.


Machakos Project Studies: Agents affecting health of mother and child in a rural area of Kenya. XIV. Growth pattern or rural Akamba pre-school children.

Between June 1974 and February 1977, in one eighth sample of the Machakos Project area, weight and height were determined in all 1-60 months-olds. This resulted in 568 subjects producing averagely 9.3 monthly growth data over an average period of 22.2 months. Only subjects examined five times or over were considered. Weighing and measuring were done by home visiting fieldworkers. Growth in the first six months closely followed the Harvard Standards of weight-for-age (W/A) and height-for-age (H/A). In the course of the next six months this dropped until about 83% for W/A and 92% for H/A, to stay at these levels until the sixth year. In the group which persistently grew over 88% for W/A these values were 91.5% for W/A and 94.8% for H/A. This group is thought to represent the local standard for optimum growth. In the group which persisted at levels below 75% of W/A a distinction was made between normal slow growers and PEM cases. In both W/A was more compromitted than H/A. Children persistently or episodically under W/A 70% were considered malnourished; their incidence in the 1-5 year group was between 4.5 and 6.5%. There was no reason to put the PEM level above 70% of W/A; This should be used as a cut-off level for screening PEM cases. A diagram is presented to visualize the successive age cohorts simultaneously for W/A, H/A and W/H as regards their position to the respective Harvard Standards, indicating percentages of positive and negative deviators.


Biting activity by Aedes egypti mosquitoes in guinea-pigs. An experimental model for screening the effect of some systemically administered compounds.

The Aedes egypti mosquito fed consistently on guinea-pigs in a 2-hour period (n = 61), the mean percent feeding rate (+/- S.D.) being 88.84 +/- 9.32. Of a total of 34 different compounds systematally administered in guinea-pigs and tested for their effect on the mosquito biting rate using the above model, five: heparin, sodium fluoride, aminocaproic acid, thiourea and dithiocarb partially reduced the biting rate. The results are consistent with the view that certain aminoacids or proteins of blood or tissues serve as 'pheromones' attracting the mosquito to guinea-pigs.


Developing world. Child rearing practices in an Indian slum.

Our study has revealed the strong influence of tradition on child rearing practices in an Indian slum community. It is made clear that health education is essential to correct malpractices. Though the mothers were knowledgeable about the supplementary feeding they did not put the ideas into practice.


[Plication of the nuclear membrane and its derivatives in the polyploid cell nuclei of the rat trophoblast].

Folding pattern of the nucleus envelope and intranuclear membrane structures in trophoblast giant cells and in trophoblast of the intermediate region of the rat placenta have been studied. Cells of the intermediate region of the placenta demonstrate deep invaginations resulting in the appearance of lobulated nuclei. Invaginations of the nuclear envelope pass on a narrow fold made by an inner nuclear membrane. The polyploid nuclei of trophoblast giant cells have superficial folds and deeper finger-like invaginations in their envelopes. Such folding trophoblast nuclei in two populations examined are met throughout the whole ontogenesis of the cell. In the giant cells, individual intranuclear tubes or their accumulations are seen. The tubes are made by a unit membrane and are surrounded with a matrix. The nuclear chromatin, diffuse or condenced, is in association with the tube surface. The tubes are met near the nucleolus and on its surface, where these are surrounded with the granular component of the nucleolus. In the trophoblast of the intermediate region of the placenta, intranuclear concentric membranes have been found; made of paired membranes, intramembranous space being filled with electron dense matrix. The concentric membranes lie separately in the karyoplasm, not being associated with the chromatin.


[Fragmentation of polyploid nuclei in the giant cells of the rat trophoblast. I. The ultrastructure of the nuclear fragments].

Electron microscope study of the nuclear fragments in the rat trophoblast has demonstrated that the division of the trophoblast giant nucleus results first in the formation of a multinuclear cell. Each nuclear fragment is covered with its own nuclear envelope made of two membranes with numerous pore complexes. The chromatin in these nuclear fragments is condenced with various degrees of condensation, which depends on the step of placenta development, cell differentiation and the degree of nuclear fragmentation. The nuclear ultrastructure in nuclear fragments also depends on the degree of nuclear fragmentation and on the level of chromatin condensation. The nucleolus has no granular component. On large fragments, with lower chromatin condensation the nucleolus is not homogenous being made of fragments of more and of less electron dense fibrilles. Small light lacunae are seen in the nucleolus where chromatin threads and strands pass on. With a high chromatin condensation in the nucleus, round small nucleoli look homogenous being made of moderately electron dense fibrilles. Products of chromosome activity have been found in the nuclear fragments: accumulations of minute granules (d = 15--20 nm), perichromatinous granules (d = 35--40 nm), and fibrillar nucleolus-like bodies. In the multinuclear cell, made as the result of fragmentation of the initially giant nucleus, all the small nuclei are first arranged very close to each other, so that the contours of the neighbouring nuclei coincide.


[Cultivation of whole brain slices: a description of the method and the results of its use for culturing the rhombencephalon and midbrain of chick embryos].

A method and device for obtaining embryo brain slices are described. Results of cultivation of slices of rhombencephalon and mesencephalon are presented obtained in accord with a proposed technique of the "swimming float" (Olenev, 1979). With this cultivation, original topographical relations between brain nuclei and fibrillar tracts remain unchanged that enables us to compare these cultures with histological sections of brain to identify strictly the structures being cultivated. Cultured neurons of nuclei of XII and VIII pairs of cranial nerves have been first described in addition to various divisions of the reticular formation commissura cochlearis dorsalis. Compared to cells examined in the in vivo conditions, neurons of the nucleus cochlearis laminaris, grown in tissue culture conditions, do not make plate-forming structures; dendrites of the neurons of III layer of tectum opticum do not develop. This may be explained by the absence in vitro of any stimulating influence from the acustic ganglion fibres and ganglion cells of the retina on these morphogenetic processes.


[Dependence of frog epithelial cell and neuron survival time on the concentration of certain substances].

The frog cornea epitelial cells, nervous cells of spinal ganglia and of urinary bladder have been found to survive in vitro, in the presence of subtoxical concentrations of chloral hydrate, urea, ethanol or methanol added to the Ringer solution, longer than control preparations. The above drugs added both in lower and higher concentrations lead to cell damages, thus reducing the cell survival time, which was tested by the capacity to deposit granules of a vital dye - neutral red.


[14C-leucine incorporation by the nerve and glial cells of a cultured spinal ganglion].

Spinal ganglia of adult rabbits were cultured in the routine and protein synthesis precursors-enriched media. On days I and 4 of cultivation, the intensity of 14C-leucine incorporation in protein and in acid soluble fraction of nerve and glial cells was determined. The tissue of the spinal ganglion keeps incorporating 14C-amino acid, into neurons and glia, for all the tested periods of cultivation with both the media employed. The curves of incorporation into the above fractions of nerve and glial cells cultured in the routine medium display similar patterns of changes, whereas those obtained from the enriched medium observations appear to be anti-fasic. The enrichment of the medium results also in less pronounced fluctuations in the intensity of the labeled amino acid in protein and 14C-leucine pool, on the tested periods of cultivation, which may provide more stable conditions of the explant's survival.


[Effect of RNA and histone preparations on the properties of lymphoid cells].

Preparations of RNA and histones change the electrophoretic mobility of lymphoid cells, the intensity of their respiration and anaerobic glycolysis, and thermo-merchanical properties of DNA-complexes isolated from lymphoid cells. RNA and histones exert their influence on the properties of DNP-systems and the rate of anaerobic glycolysis in the opposite manner. But both these preparations depress the electrophoretic mobility and oxygen consumption.


[Weakening of the ultraviolet ray-induced unscheduled DNA synthesis in human lymphocytes in extreme old age].

The intensity of unscheduled DNA synthesis was studied in UV-irradiated (10--15 J/m2) peripheral blood lymphocytes of 80--90 years old persons. In these extreme old age persons, reparative DNA synthesis was found sufficiently reduced in comparison with that in middle aged (20--43 years old) ones. The role of DNA repair processes in ageing is under discussion.


[Primary mechanism of a reduction in the intensity of extremely weak mitochondrial luminescence in the process of chemical hepatic carcinogenesis].

The induced chemoluminescence in rat liver mitochondrial preparations was studied in the course of 2-acetylaminofluorene or N-nitrozodiethylamine induced hepatocarcinogenesis. As follows from the literature, the intensity of chemoluminescence is representative of catalase activity, i. e. of one of mitochondrial enzymes. Beginning from the stage of stimulation of pretumor cell proliferation, the course of carcinogenesis is caracterized by a progressive decrease in the intensity of chemoluminescence. An adrenomimetic noradrenaline induced a similar effect, whereas isoprenaline and alpha-adrenoblocator pirroxane stimulated chemoluminescence of mitochondria preparation in the intact rats. Ortobenzoquinone being oxidated with H2O2, noradrenaline and isoproteranol were deprived of oxidative activity. It is suggested that inhibition of mitochondrial catalase activity with endogeneous noradrenaline constitues a primary mechanism of the decrease in chemoluminescence intensity.


Use of oxygen for optimizing decompression.

For over 70 years, decompression has been facilitated by the use of elevated oxygen partial pressures. Oxygen has been administered even though little is known about the proper dosage or the way in which this benefit is derived. The historical literature indicates that there is an envelope or narrow range of oxygen partial pressures that can be used. If the oxygen is too low, the incidence of decompression sickness increases; if the oxygen is too high, oxygen poisoning becomes a problem. The present study was designed to explore this oxygen envelope and to define the relationships between oxygen partial pressure, exposure time, and pressure, and to delineate their effects on pressure-reduction limits. To define the ED50 (the effective dose that produced signs of decompression sickness in 50% of the animals), we exposed 820 female albino rats to 42 experimental conditions. Results suggest that the optimum oxygen level and the size of the oxygen envelope both depend on the ambient hydrostatic pressure and the exposure time. For short "shallow" exposures, the optimum oxygen level is high and the oxygen envelope is large; for long "deep" exposures, the optimum oxygen level is reduced and the envelope is restricted.


Rate of pressure change and hyperbaric bradycardia in the mouse sinus node.

Sinus node preparations from mice were hydraulically compressed at 10, 100, and 500 atm x min-1 in Tyrode's solution at 27 degrees C. At the highest compression rate, both a delay and a more pronounced beating frequency response to pressure was seen. The delayed reaction is ascribed to either adiabatic effects or a time-delay in conformational changes in the pacemaker cell membrane. The potentiating effect of a high compression rate could be eliminated by autonomic blockade (atropine and practolol).


Diffusion-dependence of pulmonary gas mixing at 5.5 and 9.5 ATA.

Gas-phase diffusivity is inversely proportional to pressure, so mixing of inspired gas in the lung can be expected to be poor in hyperbaric environments. Subjects performed multiple-breath wash-in of a mixture (4% each of SF6, Ar, Ne, and He; 21% O2, 63% N2) at 1.5, 5.5, and 9.5 ATA. At the higher pressures there were marked differences of concentrations between the indicator gases, measured by mass spectrometer at the mouth during a single expiration. Compared to heavier gases, light gases fell from dead space concentration to the "alveolar" level sooner, had a flatter plateau, and had a lower average expired concentration, indicating that more of the light gases were retained in the Functional Residual Capacity (FRC) after the breath. However, wash-in rates for the indicators were about the same; a rapid initial rate for He diminished so that it was about the same as the SF6 rate, because in later breaths a back pressure developed for He. The findings illustrate the basic principle that the amount of gas that diffuses from one location to another in a container depends not only on diffusivity, but also in an interdependent manner on concentration gradient, time for diffusion, and configuration of the container.


Effects of immersion and static lung loading on submerged exercise at depth.

The effects of static lung loading in the range +20 cmH2O to -20 cmH2O was investigated in 3 male subjects breathing air during submerged exercise in the prone position at pressures ranging from 1.45 ATA to 6.76 ATA. Both maximal and submaximal exercise was performed and dry controls were done at 1.45 ATA. A low-resistance bag-in-a-box breathing apparatus (less than 1.25 cmH2O/liter/s at 8 g/liter density) was used. Static lung loading had little effect on maximal or submaximal VO2, VCO2, VE, heart rate, or end-tidal PCO2, while increased breathing gas density did affect these parameters to a larger extent. Imersion per se reduced the VE at a given level of VO2 and increased both the VT and VA at a given VE. Increasingly positive static lung load increased VC and ERV both during rest and exercise. Exercise-induced dyspnea was experienced and scored. At submaximal VO2 levels up to 2.5 liter/min this dyspnea did not limit exercise at any depth, but during maximal exertion at 6.76 ATA (VO2 from 3.45--3.77 liter/min), dyspnea became work limiting in several cases. Static load had a marked effect on dyspnea and a load of +10 cmH2O produced the least dyspnea, enabling all subjects to perform maximal exertions for 5 min at 6.76 ATA. The 15-s MVV was performed at all depths and static loads and neither it nor the VE/MVV ratio correlated with the degree of dyspnea.


Urinary excretion of water and electrolytes during open-sea saturation diving to 850 fsw.

The dive was carried out in the open sea to a depth of 850 fsw (26.7 ATA) for 6 days (DD 1--6) in the saturated mode, with personnel transfer capsule (PTC) excursions between 0 and 150 fsw and diver excursions between 0 and 50 fsw from the saturation base. Each diver had two excursion dives on alternate days. Although each PTC excursion lasted approximately 7 h, the actual time spent in the water averaged 10.5 min per diver. For 12 divers, daily excretion of water, electrolytes, aldosterone, and antidiuretic hormone (ADH) was studied, along with plasma composition (including prolactin), before, during, and after hyperbaric exposure. A significant increase in urine flow was observed on DD2--4 (1604 ml/day predive vs. 2300 ml/day on DD 4; P less than 0.05), after which the degree of diuresis decreased to about 1800 ml/day. Urine osmolality changed inversely with urine flow, with the lowest value of 532 mOsm/kg on DD 4. During the postdive period, both urine flow and urine osmolality returned to the predive level. The endogenous creatinine clearance was maintained at about 200 liters/day throughout the dive. The fractional excretion of Na+ remained unchanged while that of K+ increased significantly during hyperbaric exposure, thus decreasing the urinary Na+/K+ ratio. The fractional excretion of total osmotic substances showed a small hyperbaric exposure. Body weight decreased progressively during the initial 4 days of pressure exposure, equalling 2.6 kg on DD 4. These findings suggest that the observed diuresis may be accompanied by a net loss of body water. Neither the plasma prolactin level nor urinary excretion of aldosterone and ADHshowed any consistent change throughout the dive. It thus appears that, although there is a small osmotic component, the observed diuresis is primarily due to the ADH-independent inhibition of fre water reabsorption from the collecting duct by means of a mechanism yet to be identified.


Divergent effects of catecholamines on peritoneal mass transport.

In rabbits, intravenous vasopressor doses of dopamine augmented peritoneal clearances of creatinine and urea, suggesting increased mesenteric blood flow and possibly augmented permeability. Intraperitoneal dopamine also accelerated peritoneal transport of urea. Solute transport across the peritoneum was decreased by intravenous infusion of 1-norepinephrine. Intraperitoneal administration of the alpha-adrenergic antagonist phentolamine partially abolished the augmentation of peritoneal clearances induced by intravenous dopamine. The results suggest that in patients undergoing peritoneal dialysis who require vasopressor therapy, dopamine should be preferred to norepinephrine.


Platelet turnover studies associated with left ventricular assist device (LVAD) implantation.

Calves given LVADs have been studied to determine changes in platelet turnover induced by the device and modified by time and anticoagulants. Passivation with time occurs but is surprisingly incomplete even one month later and despite coumadin, aspirin and dipyridamole. Without these drugs, enhanced platelet turnover and local thrombus formation on the device is exaggerated. Sequential platelet turnover studies may be useful to quantitate, monitor and/or predict thromboembolic events.


Thermodynamic studies of cellular adhesion.

Cellular adhesion of granulocytes and of platelets to solid substrates of different surface tensions has been studied from a thermodynamic aspect. A simple thermodynamic model predicts that cellular adhesion should increase as the surface tension of the solid substrate increases provided that the surface tension of the liquid medium in which the cells are suspended is lower than the surface tension of the cells themselves. If, however, the surface tension of the liquid medium is higher than the surface tension of the cells, then a decrease in cell adhesion with increasing substrate surface tension can be predicted. These predictions are completely substantiated by granulocyte adhesion tests in which the surface tension of the suspending liquid medium is varied through the addition of different volumes of dimethyl sulfoxide (DMSO). Platelet adhesion experiments also confirmed these predictions, the only difference being that it is not possible to obtain a suspending liquid medium with a surface tension higher than that of platelets themselves, as a consequence of the exudation of surface active substances by the platelets.


Factors influencing survival and successful weaning from clinical ventricular bypass with local heparinization and blood filtration: an analysis in 21 consecutive patients.

A simple circulatory support of transapical ventricular bypass type with nonpulsatile pumping and regional heparinization in 21 patients has revealed that several factors contribute to the patient's outcome. The duration of the bypass was not an essential determinant of prognosis and patients supported for 5--8 days could be weaned from TALVB. Those patients who could maintain steady hemodynamics with flow rates of 30--40% of cardiac output, were usually successfully weaned. Patients who required longer support with high flow rates (60--80% or over) had less probability of being weaned. Persistent or preexistent dysfunction of vital organs, as manifested by renal failure, brain damage, respiratory failure and infection, were main factors determining unsuccessful weaning. The complications related to pumping itself, thromboembolization, bleeding, infection and blood damage, were much less frequently observed with this type of support. The simplicity and less time consuming surgical technique for cannulation and, in addition, less harmful procedure of decannulation and avoidance of thrombus formation were directly related to the improved prognosis.


Efficacy of systolic vs diastolic pulsation beyond severe coronary stenosis flow.

This paper describes the superiority of systolic pulsatile selective coronary perfusion as compared to diastolic pulsatile coronary perfusion in improving flow beyond ischemia-producing coronary artery obstructions in the working heart. The practical implications for use in coronary support perfusion systems are discussed.


Computational stress analysis of cup replacement hip arthroplasty.

A two-dimensional finite element model of a total surface replacement hip arthroplasty was utilized to study the performance characteristics of the prosthesis by means of stress analysis. No significant changes occur in stress field distribution following resurfacing arthroplasty in the proximal femur. Local bending phenomena appear to occur in the femoral component under static loading. Prosthesis-cortical bone continuity at the femoral neck does not affect stress field distribution. Finally, trochanteric osteotomy causes a change in the stress field distribution of the proximal femur that may be a significant factor in femoral neck fracture.


Total artificial heart implantation in calves with pump on an angled port design.

The APP was employed in our 21st TAH calf and has now been implanted in a total of 11 animals. The APP has a dynamic stroke volume of 105 ml, an ejection fraction of 75%, and a peak flow of 14 L/min. The TAH features 2 APPs which have polysulfone cases and contain smooth, seam-free polyurethane sacs. Concavoconvex Bjork-Shiley valves are used. The pumps are pneumatically driven but may be easily converted to pusher-plate drive. A pneumatic drive console and an automatic control unit complete the system. The automatic control unit permits independent control of the right and left hearts as a function of left atrial and aortic pressure respectively. The average survival of the APP TAH calves has been 65 days. Hematologic study has revealed basically normal results with minimal elevation of serum hemoglobin and lactic acid dehydrogenase (LDH), indicative of a low level of hemolysis. Elelvation of central venous pressure (CVP) and total blood volume continue to be a problem with some TAH calves but not all. The APP has led to a dramatic increase in duration of survival and decrease in thromboembolism.


A volume sensor for a pneumatically driven LVAD.

The volume sensor has proven to be a valuable tool in the operation and characterization of our pneumatically driven LVAD. It compensates for the decoupling between driver and LVAD that occurs in pneumatically actuated LVADs due to gas compressibility. Uses to which we have put the volume sensor represent only a small fraction of the potential applications. Additional uses contemplated include: Use as an alternate or backup for the R-wave detection network currently used to achieve synchronization with the natural heart. This could be done by starting the LVAD ejection phase when the filling flow rate drops below a given threshold, indicating that the left ventricle has finished filling the LVAD. Use for feedback for closed loop control of plate motion. Such control could reduce actuation delays without overdriving the LVAD. Use as a diagnostic tool to aid in the study of the LVAD and its interaction with the cardiovascular system. When used in conjunction with information on left ventricular, aortic, and drive pressures, it is possible to determine the resistance, inertia and compliant characteristics of the major elements of the LVAD and the vascular system to which it is joined.


Comparative study of rigid vs flexible pneumatic artificial blood pumps.

For HR in the range of 70--110 beats/min, and same driving conditions, the pump with rigid housing produced a maximum of 15% greater CO than that with the soft housing, against an arterial pressure of 125/75 mm Hg. All 3 pumps exhibited greater sensitivity in function curves for HR in the range of 90--110 beats/min. The greatest sensitivity point in the function curve, for the rigid housing pump was found to be independent of HR change in the range of 90--110 beats/min. However, with an increase in HR the function curves shifted to the right in the case of soft housing pumps. In other words, greater atrial pressure was required to obtain the same CO with an increase in HR. The linear relationship found between CO and HR in flexible and soft housing pumps was very advantageous for controlling CO, whenever such change was required. In all 3 hearts there was a decrease in pulse pressure with an increase in HR. The decrease in pulse pressure was primarily due to the increase in diastolic pressure, while systolic pressure remained almost constant at all HRs. Since these experiments were conducted in a test circulatory system using an aqueous-glycerin solution, information on the degree of hemolysis was not addressed in this report.


Optical monitor of glucose.

Methods have been described to noninvasively monitor the glucose of the aqueous humor, a fluid with glucose in constant equilibrium with the bloodstream. A feasibility study has been performed showing that the optical rotation of the aqueous humor reflects aqueous humor glucose concentration in the range of hypo- and moderately hyperglycemic conditions. Preliminary data show that specificity for glucose may be enhanced by simultaneously measuring the optical rotation at 984 nm and 775 nm.


Blood recirculation during hemodialysis with a coaxial counterflow single needle blood access catheter.

1. The average and the range of blood recirculation during hemodialysis employing a coaxial counterflow single needle blood access catheter are markedly reduced compared to those observed in the same patients using a standard "Y" type needle and external flow direction control device. 2. In a large group of patients, the average measured recirculation of blood of 3.8% at a blood flow rate of 200 ml/min is sufficiently small as to have little or no effect on the efficiency of dialysis. 3. Recirculation increases with increasing extracorporeal blood flow rate but remains sufficiently low to not significantly affect increased dialysis efficiency obtained at higher blood flow rates. 4. The coaxial counterflow single needle catheter permits single fistula puncture, eliminates the need for a flow direction control device, and is associated with negligible blood recirculation. It offers a most attractive alternative to both double needle and present single needle blood access techniques for hemodialysis.


Simplified arteriovenous fistula construction with tissue adhesive.

A technique is described for the construction of A-V fistulae for hemodialysis by performing an end-to-end anastomosis between artery and vein by means of a cyano-acrylate tissue adhesive. The method is quick and easy, provides for good results, and has been free of complications.


The basilic vein fistula for vascular access.

The basilic vein fistula provides reliable vascular access for chronic hemodialysis therapy. Early morbidity includes edema and mild pain. Ischemic complications have not developed in this series. Patency has been excellent in the initial period and no patient has yet developed infection, aneurysm or venous fibrosis, although longer follow-up is necessary. The use of the autogenous basilic vein fistula in patients unsuited for forearm arteriovenous fistulae is supported by these results. Long-term results which would support continued use of this modality would include an expected lower incidence of infection due to the absence of a foreign body and the inherent healing property of viable tissue, and improved long-term patency attributable to the absence of a venous anastomosis.


Hemodialysis with glycerol dialysate.

Glycerol has a rate and volume of distribution similar to urea. Thirty-six mM glycerol in the dialysate prevents the fall in serum osmolality but does not decrease symptoms or improve the vascular stability of patients on chronic hemodialysis. We suggest that the benefits of mannitol, sodium and glucose in preventing or reversing symptoms during chronic dialysis are due to their extracellular distribution.


Induction of hypothermia in mice by semi-artificial cells containing indolyl-3-alkane alpha-hydroxylase.

The administration of red cell ghost encapsulated indolyl-3-alkane alpha-hydroxylase (an enzyme which destroys tryptophan by oxidation of the side chains) in CD-1 female mice causes effective tryptophan depletion in plasma and brain and induces hypothermia by probably decreasing the serotonin concentration in brain by decreasing the concentration of its precursor, L-tryptophan.


A volume controlled apparatus for ultrafiltration and hemofiltration with acetate or bicarbonate solutions.

To meet a growing need, a single dialysis apparatus has been developed that can easily be employed by conventionally trained staff to perform volume programmed ultrafiltration hemodialysis, sequential ultrafiltration-hemodialysis, hemofiltration, or any combination of these with either acetate or bicarbonate based dialysate. Continued studies will be necessary to establish its full suitability for general use. However, we feel that the investigations of the various modes of dialysis therapy that this device makes so readily available show great potential for improving the treatment of ESRD.


Hemodynamics of isolated ultrafiltration in chronic hemodialysis patients.

Six patients on maintenance hemodialysis were investigated by direct determination of hemodynamic changes induced by UF. Our results show: 1. Despite a significant fall in ECF and PV, the PV/IF ratio was unchanged indicating absence of major fluid shifts between intravascular and extravascular compartments. 2. The rise in CPV/TBV ratio observed indicates central redistribution of intravascular fluid suggesting venoconstriction. 3. CPV and hence CO was maintained so that a stable MAP resulted.


Defining indications for artificial organ support in respiratory failure.

Patients with acute respiratory failure who have high mortality risk can be analyzed according to the methods outlined above. Some (but not all) of the high mortality risk patients can be identified early in the course of respiratory failure. Temporary support with ECMO is indicated in these patients if there are no signs of irreversible damage.


Oxygen permeability in ultrathin and microporous membranes during gas-liquid transfer.

The apparatus described here offers a useful system for measuring membrane oxygen permeabilities with the membrane in contact with liquid on one side. Results using this system indicate that liquid migration into the pores of microporous membranes can play a significant role in reducing their permeability to oxygen.