[Colonic motility].

Intraluminal manometry with microballoons or perfused catheters as well as determinations of transit time are the most important methods in the study of colonic motility. Motility recording is complementary to other methods of investigation; but we cannot yet prove or disprove the diagnosis of any disease of the colon by studying motility. In further motility studies, the development of a technique for the diagnosis of the irritable bowel syndrome, the most frequent gastrointestinal disease, should have priority. According to our present knowledge, motility disturbances of the colon may be classified as follows: achalasic colon, hypersegmenting colon, hyposegmenting colon and disturbances of the defecation reflex.


[Manometry of the anorectum].

Manometric studies of anorectal continence have been performed in pediatry and pediatric surgery since more than fifty years. The method permits a differential diagnosis of chronic constipation as well as an objective analysis of different degrees of severity in cases of anorectal incontinence. By manometric studies it is possible to show, whether a traumatic lesion is situated at the puborectalis sling or caused by a maximal delated rectum, a loss of sensitivity or disturbances of the anorectal sphincter. Therefore no therapy should be done without previous electromanometric analysis. The diagnose is base on the registration of different variables which are reliable to the rectal - puborectal- and anorectal sphincter function. It is a semiquantitative method like the EMG or the EEG. Outside the anorectal area manometric investigations are important as well to control sphincter function in the upper gastrointestinal tract and the lower  abgenital urinary tract. For that reason special electromanometric laboratories should be established in greater pediatric hospitals and centers of pediatric surgery.


[Morphologic studies on the toxicity of sulfated and nonsulfated lithocholic acid in the isolation-perfused rat liver].

The isolated liver of male Sprague-Dawley rats was perfused by means of media containing lithocholic acid, taurolithocholic acid, lithocholic acid sulfate and taurolithocholic acid sulfate. 150 minutes later the tissue was being examined light- and electrone microscopically. After LC and TLC perfusion considerable alterations were found in the bile capillaries, in the ergastoplasm and minor ones in mitochondria. After perfusion with sulfate esters the tissue was unchanged. Our investigations have shown that sulfation provides a highly effective mechanism of detoxication in rats; but detoxication results not only in a decrease of reabsorption of excreted lithocholic acid sulfate esters but sulfation tenders the very lithocholic acid untoxic for the liver cell. The primary point of action of lithocholic acid seems to be the lipoprotein membrane.


[Gastrointestinal hormones. I. Hormones of the gastrin group].

Gastrin is a peptide hormone originating from G-cells of the antrum, the duodenum and the proximal jejunum. From extracts of gastrinomas and from sera of hypergastrinaemic subjects several gastrin molecules could be isolated which were nominated as "mini gastrin" (G13), "little gastrin" (G17), "big gastrin" (G34) and "big big gastrin". Antisera used for radioimmunological gastrin determinations should be characterized with respect to their specificity, as differeing affinity towards the various gastrins and towards CCK-PZ influences the results of the assay and thus the comparability with values of other laboratories. Gastrin is released by direct vagal stimulation of the antral G-cells and by local chemical and physical stimuli in the antrum and duodenum; probably an oxynto-pyloric reflex also exists. Gastrin stimulates in physiologic doses gastric acid secretion and, as shown in dogs and cats, reveals a trophic action on parietal cell growth. H+-secretion and gastrin release are connected by a feed back mechanism, insofar, as a decrease of intragastric pH below 3 inhibits endogenous gastrin release. Hypergastrinaemia has been demonstrated in patients with gastric anacidity or hypo-secretion, benigne pyloric stenosis, uraemia, short bowel-syndrome, gastric and duodenal ulceration and in patients with gastrinomas (Zollinger-Ellison-syndrome). Hypergastrinaemia in combination with hypersecretion exhibits clinical significance in patients suffering from Zollinger-Ellison-syndrome or excluded antrum syndrome which are due to autonomous gastrin release. The differential diagnosis between these syndromes and other diseases, in which hypergastrinaemia is not associated with gastric hypersecretion, can be achieved by several tests using calcium infusion or intravenous application of secretin and glucagon. The significance of elevated gastrin levels in patients with duodenal ulceration (DU) is pointed out. In DU-patients basal and postprandial hypergastrinaemia has been observed. In these patients gastrin release from gastric and extragastric sites is increased. In these patients hypergastrinaemia due to extragastric gastrin release could cause gastric hypersecretion at a time, when the stomach already has emptied. Furthermore parietal cell hyperplasia could be the result of chronic hypergastrinaemia.


Fine structure of microgametogenesis of Eimeria ferrisi Levine and Ivens 1965 in Mus musculus.

The microgamogony of Eimeria ferrisi from experimentally infected mice was investigated with the electron microscope. Microgamonts were recognizable by the presence of peripherally arranged nuclei and the presence of single or paired centrioles between each nucleus and the limiting membrane of the parasite. Often an intranuclear centrocone directed toward the centriole was present. Differentiation of the microgamete began when elevations of the limiting membrane, which indicated the commencement of flagellar development, appeared above the centrioles. This event was accompanied by the segregation of nuclear content into a dense osmiophilic portion and an electron-pale portion. Then followed a gradual protrusion of the dense portion of the nucleus and developing flagella into the parasitophorous vacuole. A dense ring developed at the base of the differentiating microgamete, resulting in the formation of a stalk which was occupied by the residual portion of the nucleus. Fully developed microgametes became detached and occupied the parasitophorous vacuole along with residual cytoplasm. Microgametes had an anterior perforatorium, a dense elongate nucleus, with an anteriorly positioned mitochondrion in a small groove of the nucleus. Usually two flagella were present but one microgamete appeared to have three. Polysaccharide first appeared when differentiation was in progress and increased until large numbers of granules were present in the microgamont cytoplasm.


Amino acids in eight species of Monogenea.

The ethanol-extractable amino acids of several species of Monogenea were analysed. In the Monopisthocotylea levels were high ( greater than 1,200 micronmoles/g/ethanol extracted dry wt); in the Polyopisthocotylea lower amounts were present (196-562 micronmoles). High proline levels were present in parasites of hosts from a marine environment but low in freshwater forms. No correlation between diet and proline content was observed.


Studies on Culicoides species of Nigeria. VII. The biology of some Nigerian Culicoides species.

During field investigations into the biology of Culicoides species of Nigeria, 8,795 newly emerged Culicoides comprising of 20 species were caught with emergence traps at the Teaching and Research Farm of the University of Ibadan. Culicoides imicola Kieffer was the most predominant followed by C. quinquelineatus Goetghebuer and C. endelini Endeline. Two groups of Culicoides species were recognized. These were those breeding only during the rains with emergence peaks in June and August and those breeding throughout the year with low emergence during the dry season. Rainfall, temperature, relative humidity, the soil pH and its organic and mineral contents were found to influence Culicoides breeding. Low or traces of rainfall extended over 1-2 h were observed to be more favourable for Culicoides development than heavy rainfall which ended quickly within 1/2 h. A greater proportion of the Culicoides emerged during the night. It was concluded that the optimum temperature range for Culicoides emergence was 23-27 degrees C and optimum range of relative humidity 80-90%. Larvae were abundant on the soil throughout the year with a peak during the dry season; the seasonal abundance of pupae was similar to that of newly emerged adults. Although the fat-bodies of all the dissected newly emerged Culicoides were large, full and conspicious, those of about half of the Culicoides dissected in February and March contained larger, fuller and more conspicuous fat-bodies. It is suggested that the presence of such accumulated fatbodies during the onset of the rains immediately after the hot dry season signifies hibernation in these species.


Otitis media: a review.

We have presented recommendations for diagnosis and management of otitis media in children based on a comprehensive review of the pertinent medical literature. For an entity that is so common, there still remain amazingly large numbers of areas of controversy. We have also attempted to stress the importance of appropriate therapy and adequate followup as being very important in the management of otitis media. Newer concepts, particularly the use of the impedance bridge tympanogram, have been mentioned. With all the above background information in mind and with considerations for what is practical for the patient and the medical community, we would recommend the following as the acceptable minimal care for patients with otitis media. When the diagnosis of the acute otitis media is made on the basis of physical findings of myringitis, and/or middle ear fluid, and/or rupture of the tympanic membrane, the following treatment course is advisable: Neonates Culture of middle ear fluid if possible. Ampicillin 200 mg/kg/day intramuscularly. Gentamicin 3/5mg/kg/day intramuscularly. Hospitalize and treat until well and for minimum of seven days. Observe closely for meningitis and other infections and drug toxicity. These should be handled only by physicians experienced in dealing with patients in this age range. Appropriate work-up for septicemia should precede treatment. Switch to specific antibiotic when cultures and sensitivity available. Children. From 2 months to 6 years of age: Ampicillin 50mg/kg/day. Decongestant (if desired). Administer for ten days. Every patient with otorrhea, severe otitis and those not clinically well should be seen for followup ten to 14 days later. They should have a minimum of otologic evaluation including drum mobility. In persistent cases, audiometry and otologic referral are necessary. If patient is allergic to penicillin, erythromycin at 20mg/lb/day may be used. Trimethoprim sulfa may hold promise in the future. Tetracycline is never indicated in this age range because of side effects and high relapse rate secondary to resistant organisms. Patients above 6 years of age: Penicillin pheyoxymethyl 250 mg every six hours for ten days. Decongestant (if desired). Followup and penicillin allergy as above.


[Clinical evaluation of the results of the Sr85 test and of bone alkaline phosphatase isoenzyme activity].

Coinciding investigations of the 85Sr test and of bone derived serum alkaline phosphatases activity were undertaken in 38 patinets with locomotor system diseases. In 15 patients there was congruence between the positive result of the 85Sr test and an increased activity of B-ALP. In 5 patients there was congruence between negative outcome of B-ALP and negative 85Sr test. The activities of T-ALP, B-ALP, L-ALP and I-ALP were compared with a group of 124 healthy controls. The causes of 18 incongruent results were analysed. In rhizomelic form of ASp, active Paget's disease, osteomalacia and in some forms of osteoporosis there was congruence between increased activity of B-ALP and the positive 85Sr test over the clinically involved area of the locomotor system. In ankylosing spondylitis (without rhizomelic involvement) there may be a moderate fall of B-ALP activity but the 85Sr test is usually positive; this may correspond with metabolic activity in the paravertebral region of the ligaments. Low B-ALP activity and positive 85Sr test in MP may refer to a latent process in the bone apparatus without marked activity of osteoblasts. The fall of B-ALP may be a result of therapy or due to the reduced capacity of B-ALP to be released from the bone. In osteomalacia the rapid fall of 85Sr activity during the test is the cause by the presence of pathological osteoid which may be, even in patients with hypertension, of renal origin. A method was described permitting the evaluation of the process of active incorporation of bone minerals (after 8 days). The activity of the 85Sr test over clinically silent areas (e.g. spine) may indicate a decompensated process in the spine due to an involvement to the large joints. The two methods used in this study are metabolically different (85Sr binds to proteoglycans and inorganic structures of bone tissue, alkaline phosphatase to the activity of osteoblasts) and prove to be clinically valuable. Detailed analysis of the results makes it possible to define the stages of clinical activity of disease and to check more exactly the efficiency of the therapeutic method.


Development of the rabbit appendix. I. Electron-microscopic observations.

The progressive lymphoepithelial development of the rabbit appendix was examined by light and electron microscopy. At 5 days postnatally, the appendix wall primitively resembles the mature organ but lacks both the discrete lymphoid organization and most cell types. The dome appears to be the first recipient of  lymphoid cells. By 18 days the lymphoid nodule has become compartmentalized and lymphoid. The epithelium, although not fully developed, is in contact with the lymphocytes of the dome. The 5-week-old appendix has all the lymphoepithelial components of the adult but lacks the size of the mature organ. At all ages reported, plasma cells and dendritic cells are absent. Bacteria, thought to be essential to appendical lymphoid development, are not apparent at 5 or 18 days. The features common to central or peripheral lymphoid tissues are discussed.


Serum sulfhydryl groups in rheumatoid arthritis.

The sulfhydryl groups are chemically active parts of the protein molecule and participate in many important biochemical and metabolic processes. The present material comprised 132 patients with rheumatoid arthritis, 104 patients with other diseases and 44 controls. The patients with rheumatoid arthritis had decreased serum sulfhydryl group levels, the decrease being greater in patients with active disease. Changes in the activity of rheumatoid arthritis were correspondingly followed by changes in the serum sulfhydryl group levels. The serum sulfhydryl group levels diminished significantly with advancing age. Similarly decreased serum sulfhydryl group levels could also be observed in many other diseases.


[Study of the growth of the vertebral bodies in adolescents].

The height of the vertebral growth zones of 13 adolescents dying between the ages of 13 and 18 years was determined with the aid of an eyepiece micrometer. In addition, the proportion 'total of widths of chondrocyte columns/diameter of the growth zone' was established. In the cervical spine, the growth zones of the caudal end plates were significantly higher than those of the cranial end plates. The reverse was true for the thoracic vertebrae. In the lumbar spine, however, conditions resembled those found in the cervical spine in that the caudal end plates were higher than those of the cranial plates; yet, there was no statistically significant difference in the relative quota 'chondrocyte columns/diameter of growth zone' in this segment of the spine. These results suggest that lengthwise growth of cervical and lumbar vertebrae is more marked in the caudal than in the cranial end plates, whereas, in the thoracic spine, growth of the cranial exceeds that of the caudal end plates. Moreover, the height of the growth zones increases in a craniocaudal direction, a fact which could be related to the more marked growth of lumbar as compared to cervical or thoracic vertebrae.


[Pharmacokinetic studies after oral application of radioactively labelled D-penicillamine].

14C-labelled D-penicillamine was given orally to healthy test subjects in different dosages. The time course of serum activity was followed up to 5 weeks and the urinary activity was measured for 4 days. The obtained results equalled the sum of active substance and its 14C-labelled biotransformation products. The maximal serum concentration appeared about 2 hours after ingestion, the obtained concentrations being proportional to the dosis. Thereafter the concentration declined first relatively fast, then increasingly slower. From the 4th day after ingestion the half time of elimination was 8 days. The urinary excretion was dose dependent; the urinary concentration increasing with higher dosage. The later long half time of elimination corresponded to disappearance from the blood of the portion of the drug firmly getting attached to collagen and elastic tissue structures. The several weeks latency of onset of antirheumatic effect may be due to the fact that the portion of the drug getting attached to connective tissue accumulates slowly.


Changes in the dentition of the guinea pig following total section of the inferior alveolar nerve and vessels.

The inferior alveolar nerve was cut or the vessels entering the mandibular canal were damaged in 39 guinea pigs at 10 days of age. Possible changes in the incisors were recorded during a 100-day observation period whereafter the animals were killed and the skulls freed of soft tissues; at this time, 35 skulls were found suitable for further examination. The changes in the mandibular incisors on the operated side became observable 30-40 days post-operatively as discolourization, a 'trauma line' around the tooth, narrowing of the tooth or total loss of it's visible part. In the guinea pigs with the nerve cut (group A), such signs of maldevelopment were seen in 5 out of 19 animals, whereas the corresponding figure for the animals with the damaged vessels (group B) was 14/16. All incisors in group A and 13 out of 14 in group B recovered from the state of maldevelopment; one animal in group B showed complete loss of the incisor. The molar region was examined only from the cleaned skulls. In group A, the first molar was deformed in two animals; in group B, seven animals displayed either maldevelopment of the first molar or the first and second molar or complete loss of the first molar. No malformation of the third molar was observed. With two exceptions, the deformation or loss of molars occurred in combination with incisor maldevelopment. The malformations were considered to result from a disturbed blood supply. In group A, the dental changes may perhaps be ascribed to a short-term interference with the blood supply during the operation. The variable results in group B seem to imply that the mandibular teeth receive at least part of their blood supply from vessels besides those entering the mandibular canal. The innervation appears to have a subordinate role in the restoring of the morphology of continuously erupting teeth.


Effect of 5,6-dihydroxytryptamine on the structure of nerve fibres in the chronically isolated cat ileum.

The structure of the nerve fibres in the chronically isolated cat ileum was studied by fluorescence and electron microscopy after 5,6-dihydroxytryptamine (5,6-DHT) treatment. Residual fluorescence rapidly disappears after administration of 5,6-DHT. Under the electron miroscope, degeneration of most of the nerve processes containing a special population of 120- to 140-nm diameter granular vesicles could be observed. Also the degeneration of presynaptic terminals in the local ganglia was observed frequently. Some degenerating nerve fibres were found in the inner muscular layer, in the connective tissue surrounding Lieberkühn's glands, and in the storma of the villi. The axons (and/or other nerve processes) undergoing degeneration are assumed to belong to the serotoninergic neurons of the local ganglia. A substantial number of nerve cell processes remaining intact after 5,6-DHT treatment contain different population of vesicles: either 30- to 60-nm agranular and 100- to 120-nm granular vesicles or 30- to 60-nm agranular and 160- to 200-nm diameter neurosecretory type vesicles.


[Method of total removal of cerebral arteriovenous aneurysms].

In an attempt to improve the results of total removal of arteriovenous aneurysms from the brain the authors have been using an operation microscope and microsurgical technique for the recent 5 years. This permitted to leave the minimal number of clips on the main afferent arteries and large drainage veins of the aneurysm, thus decreasing the risk of the development of gross connective tissue capsules around the silver clips, and of the inherent disorders in the brain function. In 20 patients 2 to 8 clips were left in the brain after surgery. Nineteen patients were discharged from the clinic with improvement, or without any changes in their preoperative neurological symptoms. Two patients died. Rare epyleptic fits were observed only in one patient.


[Cryosurgical treatment of tumors of the cerebral hemispheres].

A technique of cryosurgical removal of extra- and intracerebral tumours of the hemispheres of the brain was developed. The employed cryosurgical device was provided with a cryoprobe featuring an instrument fixed in a handle and having a vacuum-insulated line of supply and removal of the cold-carrying agent (liquid nitrogen). The separation of the tumour from the surrounding brain tissue and the control of haemorrhage from the cerebral vessels was performed with the aid of a cryocoagulator connected with the cryosurgical device. An analysis of 64 cryosurgical interventions demonstrated that the employment of the cryosurgical method helps to prevent cerebrovascular disorders, and to decrease the degree of brain oedema-swelling.


[Morphology of the lymph vessels and axillary and mediastinal lymph nodes of the white rat (Rattus norvegicus)].

In this work, the authors studied the morphology of the axillary and mediastinal lymph nodes and their efferent branches in the white rat (Rattus norvegicus). The main characteristics observed were: The presence of two groups of axillary lymph nodes, one in the lateral and the other in the medial portion, and the presence of two groups of mediastinal lymph nodes, one being ventrolateral and the other dorsoventral relating to cranial precava veins. Usually, in both sides, there is a lymphatic plexus dorsally to the jugulsubclavian angle, formed by reunion of internal jugular and subclavian trunks and the thoracic duct (to the left) or the right lymphatic trunk (to the right). From this plexus, one or two branches run off and flow into the venous jugulosubclavian angle. The subclavian trunk begins in the medial axillar lymph nodes and joins to the lymphatic plexus at the internal jugular trunk or at the thoracic duct or yet at the right lymphatic trunk according to the site, and finally it may link itself directly to the venous system. The mediastinal lymph nodes at the side send branches forming the right lymphatic trunk and branches adhering to the lymphatic plexus; the left lymph nodes join to the plexus or the thoracic duct.


[Use of the hemodilution method in neurosurgery].

The results of surgical interventions conducted with haemodilution in 31 patients with brain tumours permit to conclude that in comparison with the routine transfusion methods (25 cases) this technique has several advantages in terms of correction of the disorders in the electrolyte and protein composition of the blood, and maintenance of these parameters on a safe level during the postoperative period. A beneficial effect of this method upon the circulating blood volume and on its rheological properties was observed, which improved the conditions of microcirculation.


Ultrastructure of the human aortic valve.

The human aortic valve is examined histologically by light, transmission electron and scanning electron microscopy. The observations show that the valve leaflets are multi-laminated structures, whose laminae do not have very distinct boundaries. Through the whole thickness of the leaflets, the load-bearing collagenous fibers are preferentially oriented in the transverse direction. Elastin networks are found only in the ventricular area. The leaflets attach themselves to the ventricular musculature through very dense collagenous meshworks known as the aortic ring. The whole structure is very efficient for its function of sustaining large pressures when closed and opening under minimal pressure gradients in systole.


Sexual dimorphism of bone robusticity in different strains of rats.

A quantitative method was used to establish the sexual dimorphism of bone robusticity in 10 domesticated strains of rats and in wild rats. Sexual dimorphism had its highest frequency in the pelvis, followed by the ulna, the skull, and the femur and tibia. Humerus and tail showed the lowest frequency of such sexual dimorphism. This distribution in an unspecialized mammal such as the rat, in which selective pressures are at their minimum becauses of the factor of domestication, can serve as a baseline for comparison with taxa in which selective forces are more strongly active.


Ultrastructural characteristics of tuft cells in mouse gallbladder epithelium.

Mouse gallbladder was fixed by perfusion or immersion in glutaraldehyde and/or osmium tetroxide for electron microscopy. Besides usual columnar epithelial cells there were infrequent tuft cells in the epithelium. The cells rested on the basal lamina and extended to the gallbladder lumen. The microvilli on the apical cell surface were tall and thick and there was a rich network of microfilaments radiating from the core of the microvilli to the apical and juxta-nuclear cytoplasm. Among the bundles of microfilaments there were vertically oriented microtubules in the apical cytoplasm. Although the function of the tuft cells in the gallbladder epithelium remains unknown, it is proposed that their unique morphology may reflect a specialized resorptive function involving motility of microvilli and other cell organelles.


Innervation of the carotid body, types of nerve endings and their possible significance.

The nerve endings in the carotid body of normal cats are investigated by means of serial sections. Two types of endings not described previously are especially studied: the non-synaptic bouton and the meniscus with prolongations. The first is a small nerve ending with abundant mitochondria and glycogen which is devoid of synaptic vesicles. The second is a normal meniscus which presents prolongations containing the same cytological elements of the nonsynaptic boutons. It is proposed that some menisci are lateral endings of an afferent fiber. Relating these results with well-known functional characteristics of the carotid body, the existence of axonal reflexes is suggested. These views can explain apparently contradictory facts.


An unusual case which began with subcutaneous panniculitis followed by fever, severe hepatic involvement and hyperlipidemia.

A 25-year-old man was at first dermatologically suspected as suffering from Weber-Christian syndrome because of subcutaneous panniculitis, but his skin lesions disappeared completely during the course. Hyperlipidemia, disturbances in liver function, and leukemoid reaction became remarkable and he died of subarachnoid hemorrhage eleven months after onset. Necropsy revealed subarachnoid hemorrhage at the base of the brain, lipogranulomatous and inflammatory lesions in the upper lobe of the left lung, a remarkable fatty liver, splenomegaly, pericarditis, and foam cells in the spleen, liver, and bone marrow. A comparison with 57 autopsy cases of Weber-Christian syndrome reported in the literature showed our case to be an exceptional instance of Weber-Christian syndrome, if the present case is not to be regarded as a different disease entity.


Repeat angiography in temporal contusions.

In the diagnosis of a temporal contusion bilater filling of the Sylvian vessels permits adequate comparison between the two sides. Such a comparison is important since even at a large contusion with marked upward or medial displacement of the Sylvian vessels no corresponding shift of the midline structure may exist in the acute stage. With increasing interval between trauma and angiography a shift may develop reflecting the true size of the lesion.


Hydro- and hemodynamic effects of catheterization of vessels. V. Experimental and clinical catheterization of stenoses.

The volumetric flow rate and the pressure course through free and catheterized stenoses have been analysed experimentally. The influence of the following parameters has been considered: (a) the penetration depth of the catheter into stenoses of various geometrical shapes and various dimensions, (b) the length of the stenosis, (c) the size of the annular lumen area between the catheter and the stenosis wall, (d) the geometrical shape of the stenosis. Some previous attempts to derive a simple relation between the volumetric flow through and the pressure fall across stenosis with and without introduced catheter are discussed. Clinical pressure measurements across renal artery stenoses are given, and the validity of catheter-measured pressure gradients across stenoses is discussed.


Cavography in the management of malignant abdominal tumors.

Six cases of malignant abdominal neoplasm with extensive tumor involvement of the veins form the basis of this report. One case was a child with retroperitoneal liposarcoma. Proper therapeutic management in these cases was dependent upon a complete angiographic evaluation, including cavography. This procedure is virtually without complications and should, therefore, be done routinely in cases of abdominal neoplasms for evaluation of the operability, to confirm the angiographic findings indicating intravenous tumor invasion or extravenous compression, and as a primary examination in the assessment of possible or known abdominal tumors in children.


Double contrast examination of the stomach. An improved technique.

Double contrast examination of the stomach has a greater accuracy than conventional barium meal, especially in the diagnosis of minor gastric lesions. The use of a common drinking straw with a side-hole to introduce air simultaneously with the barium suspension after gastric emptying with metoclopramide and using short acting hypotonic agents like Buscopan and Glucagon provides a practical and effective simplified technique for double contrast examination of the oesophagus, stomach and duodenum.


AHR-5850: a potent anti-inflammatory compound.

AHR-5850 is a non-steroidal anti-inflammatory compound possessing antipyretic and analgesic properties. AHR-5850 was 16.4 and 22.8 times more potent than phenylbutazone in suppressing acute (Evans blue-carrageenan pleural effusion) and chronic (adjuvant-induced arthritis) inflammation, respectively. The analgesic activity of AHR 5850 was 43 times that of acetylsalicylic acid in the Randall-Selitto assay, and 156 and 56.3 times more potent than phenylbutazone in the acetylcholine-induced abdominal constriction in mice and in the bradykinin-induced nociceptive response in dogs, respectively. Single-dose studies showed that AHR-5850 produced less gastric irritation than acetylsalicylic acid when applied topically to the exposed gastric mucosa of cats or when administered orally to rats and dogs. Upon subchronic oral administration to rats, the therapeutic ratio of AHR-5850 was twice that of phenylbutazone. This was based on the ratio of its potency relative to phenylbutazone in producing intestinal lesions to its anti-inflammatory potency relative to phenylbutazone in the adjuvant-induced arthritis.


An X-ray analysis of adjuvant arthritis in the rat. The effect of prednisolone and indomethacin.

A detailed evaluation has been made of the radiological changes occurring in the hindfeet of rats with adjuvant arthritis from 0 to 50 days after injection with Freund's Complete Adjuvant (FCA). The results were compared with concomitant foot swelling and the presence of histopathological abnormalities at the end of the experiment. In addition, the effects of oral administration of prednisolone and indomethacin administered either from one day before injection with FCA to 21 days afterwards, or from 21 to 35 days after injection with FCA, has been investigated on all these changes. The main radiological changes were osteoporosis of the tarsals and metatarsals, erosions of the tarsals and periosteal reactions in the metatarsals which were visible on day 10 and progressed up until 21-24 days after injection with FCA. Cystic fibrosis was noted in the metatarsals on day 14 and in the tibia, fibula and tarsals on day 21 and progressed to become the dominant abnormality by day 35. Cystic fibrosis and subsequent calcification, which was apparent on day 35, were the main features of the disease when the animals were killed on day 50. 10 and 30 mg/kg prednisolone and 0.3 and 3 mg/kg indomethacin both reduced the total X-ray score when administered either from day - 1 to 21, or from day 21-35, but did not at any time inhibit the osteoporosis or erosions. Their effect was mainly on preventing the cystic fibrosis and calcification which occurred later in the disease. Prednisolone and indomethacin also reduced the periosteal reaction when administered from one day before injection with FCA, but they were inactive in this respect when dosing was started on day 21 when the periosteal reaction was well established. Therefore, the results suggest that prednisolone and indomethacin inhibit the later sequelae of the disease and do not interfere with either the initial events or the disease process itself. There was a good correlation between the toal X-ray score, foot size and total histopathology score at the end of the experiment, and also an apparent correlation between total X-ray score and foot size throughout the experiment. Although this suggests that foot size is sufficient to indicate the overall reaction in adjuvant arthritis, X-ray analysis may detect clinically useful anti-rheumatoid activity which might not be evident from measurements of foot size alone.


Anti-inflammatory properties of griseofulvin.

Anti-inflammatory activity of griseofulvin has been investigated in comparison with indomethacin and flufenamic acid. In vitro, griseofulvin has been proved the most effective of these agents in suppressing the contractions of smooth muscle preparations induced by a variety of proposed mediators of inflammation, i.e. histamine, 5-hydroxy-tryptamine, bradykinin and prostaglandin E2. In vivo, griseofulvin was unable to modify dextran oedema but suppressed carrageenin oedema, although its activity was poor when compared to that exhibited by indomethacin and flufenamic acid. When tested in rat pleurisy induced by dextran or homologous serum griseofulvin was able to prevent polymorph migration into the pleural space while mononuclears remained virtually unaffected. In contrast indomethacin and flufenamic acid mainly suppressed mononuclear migration while polymorphs resulted only slightly affected. Similar results have been exhibited by the drugs when tested on mononuclear turnover in pleural cavities from normal rats. Results are discussed in the light of the clinically established ability of griseofulvin to prevent cutaneous inflammatory reactions as well as of its effectiveness in the treatment of several polyarthritic syndromes.


Ethanol and tolerated doses of Amanita phalloides protect against lethal doses of the mushroom.

Single tolerated doses of a lyophilizate from Amanita phalloides (ADL) failed to increase the survival rate of mice after the LD90 of the mushroom. Also, pretreatment with large doses of ethanol did not protect against lethal doses of APL. However, with combined administration of single tolerated doses of APL and of ethanol, the survival rate of mice after a lethal challenge with APL was increased from 13% to up to 100%. Both ethanol and APL potentiated the effect of barbiturate narcosis, but the combined pretreatment was not more effective. The protection against APL afforded by the combined regimen may be due to inhibition of activating hepatic microsomal enzymes, but biochemical studies are needed to support this hypothesis.


Dimaprit -(S-[3-(N,N-dimethylamino)prophyl]isothiourea) - a highly specific histamine H2 -receptor agonist. Part 1. Pharmacology.

S-[3-(N,N-Dimethylamino)propyl]isothiourea (dimaprit), has been shown to be a highly specific histamine H2-receptor agonist. Parallel line assays showed that in vitro at H2-receptors it had approximately 17.5% the activity of histamine on the rat uterus and 71% on the guinea-pig right atrium, with similar maximal responses; it had less than 0.0001% the activity of histamine on H1-receptors. Dimaprit stimulated gastric acid secretion in the rat, dog and cat in which it had, respectively, approximately 19,58 and 400-500% the activity of histamine. In the dog and cat the maximum secretory response to dimaprit was significantly greater than that obtained to histamine. The H2-receptor specificity of dimaprit in causing depressor and vasodilator effects was also demonstrated in the cat, in which it had 18-20% of the H2-receptor activity of histamine. Dimaprit should prove to be a very useful tool in studies examining the role of histamine in physiology and pathology. The absence of marked cardiovascular effects at doses maximal for the stimulation of gastric acid secretion, as seen in the cat studies, could lead to this compound being of value as a diagnostic agent in the measurement of maximal acid secretory capacity.


Histamine and acute haemorrhagic lesions in rat gastric mucosa: prevention of stress ulcer formation by (+)-catechin, an inhibitor of specific histidine decarboxylase in vitro.

Acute haemorrhagic lesions in the oesophagus, stomach and duodenum ('stress ulcers') occur relatively often under clinical conditions and are always dangerous to the patient (lethality rate about 70%). Since conservative and surgical treatment are without significant success up to now, prevention by adaptation to stressors or by administration of drugs seems mandatory. An improved technique for producing acute gastric lesions in rats by immobilization and a new method for assessing this disease in the animals is presented in this communication. High precision is obtained within a single experimental series especially from day to day. Since histamine was suggested to be involved in the pathogenesis of stress ulcer disease, (+)-catechin, a rather specific inhibitor of specific histidine decarboxylase from rat stomach, was tested in immobilized rats. It prevented the formation of acute gastric lesions by 80% in seven series of experiments lasting for half a year. Since the drug has low toxicity in man, it is recommended for clinical trials.


Histamine and peptic ulcer disease: histamine methyltransferase activity in gastric mucosa of control subjects and duodenal ulcer patients before and after surgical treatment.

Histamine methyltransferase (HMT) activity was determined by a modified isotope assay in biopsy specimens from gastric mucosa of control subjects, duodenal ulcer patients and after various gastric operations. Enzymic activity of male control subjects who were 'healthy' with respect to their upper gastrointestinal tract was 70.4 +/- 12.8 pmol/(min x mg protein). In male duodenal ulcer patients HMT-activity was significantly lowered by 15%; following selective vagotomy with pyloroplasty a significant increase of 14% was observed as compared to controls. The difference between values before (59.9 +/- 13.3) and after (80.4 +/- 11.7) this operation was highly significant (p less than 0.001). Experiments in a small number of patients showed that after other modifications of vagotomy elevated HMT-activities were also found, whereas after resection procedures such changes of enzymic activity did not occur. According to these results the low gastric HMT-activity of duodenal ulcer patients could play a role in the pathogenesis of a chronic peptic ulcer by being responsible for reduced histamine inactivation and - as a consequence - enhanced acid secretion. Furthermore, vagotomy seemed to influence acid secretion in human subjects not only by direct effects on the parietal cells, but also by an activation of histamine catabolism. One patient, who despite complete vagotomy showed both no reduction in acid secretion and a low gastric HMT-activity, may be the representative of a new population of peptic ulcer patients.


Influence of H1- and H2-receptor antagonists on the circulatory system and on the endogenous plasma histamine concentrations in dogs.

The effects of the H1-receptor antagonist dimethpyrindene and the H2-receptor antagonist burimamide on circulatory and respiratory parameters and on plasma histamine levels were tested in 21 mongrel dogs. Both drugs released histamine. The incidence for this effect was 10/11 in the case of dimethpyrindene and 5/10 in the case of burimamide. Following dimethpyrindene all animals showed arterial hypotension, pulmonal hypertension, decrease in peripheral resistance and hyperventilation. The portal venous pressure was increased in dogs reacting by a histamine release. Following burimamide both an initial arterial hypertension and a subsequent hypotension were observed the latter being more pronounced in the group with histamine release. In this group the portal venous pressure raised considerably. In the non-reacting animals cardiac output was elevated, probably due to a release of catecholamines. It seemed remarkable that the effect of exogenous histamine on portal venous pressure was completely blocked by dimethpyrindene, but not the action of histamine released by the drug itself. It is concluded that the effects of anti-histaminic drugs on possibly histamine-induced physiological and pathophysiological processes should be interpreted very carefully as far as their specificity is concerned.


The prevalence of angina pectoris and abnormal coronary arteriograms in severe aortic valvular disease.

In order to relate the frequency of angina pectoris to associated coronary artery disease, 66 consecutive patients with severe aortic valvular disease were studied by cardiac catheterization, including coronary angiography. Angina pectoris was found in 63 per cent of patients with predominant aortic stenosis, 62 per cent with aortic regurgitation, and 67 per cent with mixed disease. Associated coronary artery disease (larger than or equal to 75 per cent luminal stenosis) ranged from 14 to 28 per cent and averaged 20 per cent for the entire group of 66 patients. Only one patient without angina had significant coronary artery stenosis. Our studies indicate that angina pectoris is equally common in all forms of severe aortic valve disease and is usually not associated with significant coronary artery disease.


Electrocardiographic exercise test in patients with abnormal T waves at rest.

The results of submaximal ECG exercise test were evaluated in six leads recorded simultaneously in two groups of patients with T-wave abnormalities in one or more of Leads I, II, and V4-6. Group I included 185 patients with documented ischemic heart disease (IHD) and Group II 28 patients in whom IHD appeared unlikely. The test was positive in 88 per cent of patients in Group I and in 4 per cent of patients in Group II. In the majority of patients in both groups the T wave either did not change or became more positive or less negative after exercise. The pattern of exercise-induced T-wave changes was similar in patients with and without IHD, and was influenced predominantly by the physiologic effects of exercise. T-wave normalization after exercise occurred frequently in patients with and without IHD, and in patients with positive and negative exercise tests. Our results suggest that T-wave abnormalities, not caused by hypertrophy, conduction disturbances, drugs, or electrolyte imbalance, do not modify the results of submaximal ECG stress test, and that behavior of T wave after exercise does not alter the interpretation of the postexercise ECG. The independent behavior of the S-T segment and T wave after exercise in consistent with the theory that the S-T segment and the T wave are generated by different components of the ventricular action potential.


Arterial thromboembolic complications in patients with Björk-Shiley and Lillehei-Kaster aortic disc valve prostheses.

Arterial thromboembolic complications were studied in 196 patients who had either a single Björk-Shiley or Lillehei-Kaster aortic disc valve implanted. Eight patients suffered from such complications in the course of the first postoperative month and three of them died, two from myocardial infarction and one from cerebral embolism. Nineteen late thromboembolic complications developed in 18 of the 164 patients who survived the postoperative period, the incidence bein 5.9 episodes per 100 patients per year. The two valve types wer found to be equallly thrombogenic, and the rate was not lower than that in patients with Starr-Edwards aortic ball valves of series 2,300 previously studied. Particularly serious was valve malfunction caused by thrombi that limited the movement of the discs. Early recognition of this condition is essential, because the only effective therapy is removal of the thrombus. Three patients with a Björk-Shiley and one with a Lillehei-Kaster valve suffered this complecation and two died, while cerebral embolism caused a third late death. Two of the three patients who had not received anticoagulants developed thromboembolic complications, while most episodes occurred in spite of well-maintained anti-coagulant treatment. It is concluded that arterial thromboembolic complications remain a considerable problem also after aortic disc valve implantation, and that thrombotic valve malfunction is particularly serious and requires special attention.


Pathology of sinoatrial node. Correlations with electrocardiographic findings in 111 patients.

Histological study of the sinoatrial node (SAN) was performed in 111 patients in order to estabilsh correlations between the ECG findings and the anatomical lesions. This series includes both patients with sinus rhythm and patients with atrial arrhythmias. The results are as fololows: (a) the amount of nodal cells in the SAN was found to be inversely proportional to the age of the patients (p less than 0.001); (b) normal sinus rhythm was present in some cases with severe fibrosis of the SAN; (c) the present study does not support lesions of the SAN as responsible for atrial fibrillation; (d) chronic sinoatrial block was associated with extensive lesions of the approaches of the AV node or the AV node itself; (e) the auricular tachycardia-bradycardia syndrome was associated in most cases with both lesions of the main feature of the SAN lesion. The pathogenesis of these fibrotic lesions are discussed.


Ventricular buckling: a factor in the abnormal ventriculogram and peculiar hemodynamics associated with mitral valve prolapse.

Because of intractable ventricualr arrhythmias after a near-fatal episode of ventricular fibrillation, a patient with idiopathic mitral valve prolapse was subjected to mitral valve replacement. Vector analysis and intraoperative epicardial mapping localized the ectopic focus to the region of the posterior papillary muscle. The patient is alive and well two years after surgery; chronically inverted T waves have become upright. But propranolol and diphenylhydantoin are needed to prevent arrhythmias and T wave abnormalities during standing and exercise. Preoperatively, with the onset of mitral regurgitation and a second rapid phase of prolapse, the ventriculogram was deformed by abnormal midsystolic hyperkinesis at both sites of papillary muscle insertion. Postoperatively, focal hypokinesis appeared in the same areas, implying that they had been retracted by the prolapsing valve. Preoperatively, a papillary tip could be seen entering the mitral ring while coronary arteriography showed late systolic elongation of a small vessel feeding the anterior papillary muscle, suggesting that the papillary apparatus was indeed subject to damaging stress during the abnormal basal movement. Three other persons with severe mitral prolapse (but intact chordae) have had valve repacement and developed qualitatively similar changes in the ventriculogram. Papillary speciments in two showed significant fibrosis. Indication for operation in one of these was edpisodic ventricular fibrillation, which has not recurred. A spectrum of ventriculographic abnormality associated with mitral prolapse could be partly explained by hypokinesis of the papillary loops, variably disguised by retraction stress tansmitted from the billowing leaflets, translocation of blood into the expanding valve sail, and various degrees of unloading into the left atrium. Abnormal intraventicular flow may probably result from associated prolapse of the anterior leaflet and from buckling of the papillary sties toward the mitral annulus. Unusual physical findings in the operated cases and in eight other patients define a clinically recognizable syndrome in which severe prolapse abbreviates left ventricular ejection. Liability to symptoms and to progression of disease seems high in this group.


Double ventricular parasystole: intermittency and its relation to re-entrant premature beats.

Critical analysis of a case of double ventricular parasystole revealed that one parasystolic focus manifested complete protection, whereas the second focus appeared to be intermittent, protected from sinus and other impulse formation both early, as well as late, in the parasystolic cycle. The zone of protection failure, during which extrinsic impulses could penetrate into the parasystolic focus and discharge it, is observed between these early and late phases of protection. When the intermittent parasystolic focus is challenged by the other parasystolic beat, this zone is much wider and is located later in the cycle than the sinus beat. According to this observation, it is supposed that the intermittent parasystolic focus, in this case, is anatomically surrounded by two types of fibers, each showing different degrees of phase 3 and phase 4 block. The fibers located between the major fascicles and the intermittent parasystolic focus may have a shorter phase 3 and a less steep phase 4 depolarization than those located between two parasystolic foci. It is also demonstrated that during the phase 4 depolarization in these fibers around the focus, concealed conduction into this area by the sinus beat evoked exit delay of the parasystolic impulse, resulting in prolongation of the next parasystolic cycle. In this situation, a re-entry movement around the focus was predicted and, as expected, a re-entrant bigeminy coupled with the parasystolic rhythm was observed.


Survey of effects of variety and growing location of cotton on cardroom dust composition.

Electrostatically precipitated respirable dusts from six major U.S. varieties and growing areas were analyzed. From 81-95% by weight, was under 15 micronm diameter. Composition was affected more by growing location than by variety. Dusts contained 16-28% ash, 8-9% moisture, and 62-76% organic matter, including 16-31% protein and 2-12% cellulose. Inorganic composition reflected soil type and minerals. Major elements were silicon, calcium, potassium, phosphorus, magnesium, and aluminum. Infrared spectra of dusts resembled proteins, but water extract spectra did not. Possible implications concerning byssinosis are discussed.


Effect of whole-body vibration in combined axes and with noise on subjective evaluation of ride quality.

The effects on ratings of ride quality of discomfort produced by complex vibration and noise stimuli were investigated. The initial study examined effects of simultaneous vibration in the vertical and lateral axes in a simulated passenger aircraft. The second study examined the effects of simultaneously presented vertical vibration and noise stimuli. In both studies the components of complex stimuli were found to combine their effects at low levels of stimulation but to act separately at higher levels.


Enhanced diagnostic power of exercise testing for myocardial ischemia by addition of postexercise left ventricular ejection time.

To improve both the sensitivity and specificity of the multistage treadmill test, postexercise systolic time intervals were prospectively studied in 73 patients with angina-like chest pain and normal resting ST-T segments. The decision to perform coronary angiography was made independent of the exercise test. Twenty-three patients had normal coronary arteries and 50 had more than 50 percent reduction of luminal diameter of one or more major coronary arteries. The systolic time intervals were measured before and 2,4,6,8 and 10 minutes after exercise. Of all the systolic time intervals, the 4 minute postexercise left ventricular ejection time proved most discriminating between normal subjects and those with coronary artery disease. The deviations of this interval from the normal regression with heart rate both before and after exercise were used to calculate the net delta left ventricular ejection time after exercise. A net increase of more than 31 msec represented 2 standard deviations above normal. Twenty-three (46 percent) of the patients with coronary artery disease had an abnormal net delta ejection time after exercise. Twenty-five (50 percent) had a positive electrocardiographic response with a 9 percent false positive rate. Thirteen (26 percent) had only a positive postexercise net delta ejection time so that a total of 76 percent of patients with coronary artery disease were identified. Thus, measurement of the postexercise net delta ejection time a simple and useful adjunct to multistage treadmill testing.


Hemodynamics at rest and during supine and sitting bicycle exercise in patients with coronary artery disease.

To access left ventricular function and compare pulmonary capillary wedge pressure and left ventricular end-diastolic pressure in the supine and sitting positions, 20 men with angina pectoris secondary to coronary artery disease underwent hemodynamic studies at rest and during exercise in the two positions. At rest the values for cardiac index, stroke index, systolic ejection rate index and left ventricular stroke work index were lower in the sitting position; heart rate, left ventricular end-diastolic pressure and pulmonary capillary wedge pressure were similar in the two positions. All patients experienced angina during both exercise periods. At angina during supine exercise, stroke index, systolic ejection rate index and left ventricular stroke work index did not increase significantly from the resting values. In contrast, during sitting exercise, significant increases in these variables were observed. Comparison of data during exercise revealed higher values for heart rate, mean systemic pressure, cardiac index, systolic ejection rate index, left ventricular stroke work index and rate-pressure product and lower values for mean pulmonary capillary wedge pressure (20 +/- 3 versus 27 +/- 3 [mean +/- standard error of the mean] mm Hg, P is less than 0.001), and left ventricular end-diastolic pressure (24+/- 3 versus 31 +/- 3 mm Hg, P is less than 0.02) in the sitting position; stroke index and S-T segment depression were similar during the two exercise periods. Four patients had insignificant increases in left ventricular filling pressure during both exercise periods. Of the 16 patients with abnormal left ventricular filling pressure during supine exercise, only 10 had a similar response during exercise in the sitting position. There was a good correlation between left ventricular end-diastolic pressure and mean pulmonary capillary wedge pressure at rest and during exercise in the two postures.


Increased pulmonary vascular resistance with systemic hypertension. Effect of minoxidil and other antihypertensive agents.

Recent case reports suggest that pulmonary hypertension could be caused by minoxidil, a new potent vasodilating antihypertensive drug. Therefore, we evaluated the incidence and severity of pulmonary hypertension in 110 patients with systemic hypertension. Fourteen patients were treated with minoxidil for 2 to 35 months (mean 19.9 months), 15 were treated with no drugs, and the remaining 81 patients received conventional antihypertensive agents of several types. Pulmonary vascular resistance correlated positively (P is less than 0.05) with systemic vascular resistance. Minoxidil-treated patients with hypertension previously refractory to conventional therapy had slightly lower pulmonary vascular resistance than other hypertensive subjects. There was no correlation between pulmonary vascular resistance and duration of minoxidil therapy or other types of antihypertensive regimens. The positive correlation between pulmonary and systemic vascular resistance suggests the possibility of a causal hypertension relation in the two vascular beds.


Identification of sudden death risk factors in acute and chronic coronary artery disease.

Because of their potential role in the pathogenesis of sudden death, cardiac arrhythmias in patients with coronary artery disease have become the subject of increasing concern and investigation. A series of studies on the problem of ventricular ectopy as it relates to the entire spectrum of sudden death in coronary disease were carried out utilizing continuous portable electrocardiographic monitoring systems. Evaluation of arrthymias during the entire 3 week in-hospital period after acute myocardial infarction in 83 patients revealed that absence of premature ventricular contractions, including their serious forms (multifocal, paired, R on T phenomenon, frequency 5/min or greater) and ventricular tachycardia in the coronary care unit did not exclude their high incidence rate (premature ventricular contractions 30 percent, serious forms 41 percent, ventricular tachycardia 6 percent) in the late hospital phase. Because late hospital serious forms of ventricular ectopy correlated with arterial hypoxia and elevated left ventricular filling pressure in the coronary care unit and with persistent S-T abnormalities, the extent of left ventricular dysfunction and ischemia with acute myocardial infarction appeared precursors to these arrhythmias. Study of ventricular ectopy in the late hospital phase of acute myocardial infarction indicated that ventricular ectopy and particularly its serious forms and prognostic significance relative to subsequent sudden death after discharge; the extent of predischarge S-T segment alterations was greater in subjects who died suddenly than in survivors, suggesting that persistent ischemia or segmental dyssynergy, or both, predisposed to lethal arrhythmias. Among 86 patients with chronic coronary disease documented by catheterizerization, 87 percent had ventricular ectopy and 62 percent serious ventricular arrhythmias, in contrast to 34 percent and 9 percent, respectively in normal subjects; frequency of serious forms of ventricular ectopy was related to extent of coronary atherosclerosis. Correlation of standard electrocardiograms with continuous Holter electrocardiograms in 101 patients with chronic coronary disease over 24 months revealed that the former modality was insensitive in arrhythmia detection; patients free of ventricular ectopy by serial standard electrocardiograms had a 62 percent incidence rate of serious forms of ventricular ectopy and 6 percent ventricular tachycardia on portable continuous monitoring. Additional studies of patients with chronic coronary disease showed that assessment of both the type of ventricular ectopy and the setting in which it occurs provides the most meaningful characterization of risk of sudden death. These systematic series of observations identify premature ventricular ectopic beats as important and separate risk factors in coronary disease...


Noninvasive predictors of sudden cardiac death in men with coronary heart disease. Predictive value of maximal stress testing.

In a follow-up study of 1,852 men with coronary heart disease, 195 deaths occurred within the first 3 years (33 +/- 13 months [mean +/- standard deviation]). Analysis of these cases indicated that the risk of sudden cardiac death in ambulatory men with clinical manifestations of coronary heart disease may be readily estimated from noninvasive clinical and exercise criteria. The important predictors are indexes of the severity of coronary heart disease and impairment of peak left ventricular function demonstrated with symptom-limited maximal exercise. The advantages of these predictors are that they may be elicited on the initial study as well as on follow-up noninvasive examinations of ambulatory patients. The appearance of nonelectrocardiographic predictors in serial examinations may provide an indication for invasive studies and be a more important finding than the ischemic S-T reponse to exertion.


Variations in and significance of systolic pressure during maximal exercise (treadmill) testing.

Variations in clinical  noninvasive systolic pressure at the point of symptom-limited exercise on a treadmill were examined in six groups of subjects: 5,459 men and 749 women classified into three categories each. Among the men, 2,532 were asymptomatic healthy, 592 were hypertensive and 1,586 had clinical manifestations of coronary heart disease (that is, typical angina pectoris, prior myocardial infarction or sudden cardiac arrest with resuscitation). Among the women, 244, 158 and 347 were in the corresponding clinical categories. None had had cardiac surgery; all had follow-up status ascertained by periodic mail questionnaires. Reported deaths were reviewed and classified by three cardiologists; 140 deaths were attributed to coronary heart disease, 118 of them in the men classified as having coronary heart disease. The majority of maximal systolic blood pressure readings were reported to the nearest centimeter rather than millimeter of pressure. Retesting of 156 persons from 1 to 32 months later showed that pressure values agreed within 10 percent in two thirds, the overall mean difference was only 8.6 mm Hg and the correlation at maximal exercise was superior to that of the resting observations just before exercise. Hypertensive patients had a significantly greater body weight than normotensive persons. Among men, the lowest maximal systolic pressure was observed in the group with coronary heart disease; among women, the lowest mean pressure was found in the healthy group. Patients with coronary heart disease were slightly older, and only the women showed a significant correlation in maximal pressure with age. Only 5 percent of the variation in maximal systolic pressure in the patients with coronary heart disease was due to a shortened duration of exercise. Maximal systolic pressures correlated fairly well (r equals 0.46 to 0.68 for the various groups) with resting systolic pressure, and this relation was independent of the diagnosis of cardiovascular disease in both men and women. Relations between pressure and the number of stenotic coronary arteries and imparied ejection fraction at rest were examined in 22 men without and 182 men with coronary artery disease. Lower maximal systolic pressures were often associated with two or three vessel disease or reduced ejection fraction, or both. The prognostic value of maximal systolic pressure for subsequent death due to coronary heart disease was examined in the men with coronary heart disease. The annual rate of sudden cardiac death decreased from 97.9 per 1,000 men to 25.3 and 6.6 per 1,000 men as the range of maximal systolic pressure increased from less than 140 to 140 to 199 and to 200 mm Hg or more, respectively. Cardiomegaly, Q waves in the resting electrocardiogram and persistent postexertional S-T depression were more common in men with the lowest systolic pressure at maximal exercise.


Myocardial imaging and radionuclide angiography in survivors of sudden cardiac death due to to ventricular fibrillation: preliminary report.

Twenty-one long-term survivors of out of hospital sudden cardiac death due to ventricular fibrillation underwent radionuclide angiography and myocardial imaging with thallium-201. In 13 patients images were obtained at rest and after maximal treadmill exercise; 11 of these 13 (85 percent) had an image defect in one or both studies. Eleven of the 21 patients (52 percent) had a defect in the image obtained at rest. The magnitude of myocardial image defects was typically great; some patients had an image abnormality without other clinical evidence (angina, S-T depression) of ischemia. The mean ejection fraction, assessed in 16 patients with radionuclide angiography, was 0.41 +/- 0.15 (standard deviation); in 5 of the 16 ejection fraction was normal (more than 0.50) and in 3 it was severely abnormal (less than 0.25). Thus, noninvasive radionuclide studies defined a broad spectrum of ischemic and ventriculographic abnormalities in survivors of sudden cardiac death. Further application of these noninvasive studies may identify those at high risk.


Biologic and psychosocial risk factors of sudden death from coronary disease in white women.

The relation of the risk of sudden death from arteriosclerotic heart disease to psychosocial and biologic factors was studied retrospectively in 64 white women who died suddenly of arteriosclerotic heart disease and in 64 age-related neighborhood control women. All sudden deaths occurred outside the hospital within 24 hours of the onset of symptoms in women who were not incapacitated before death. Women who died suddenly were less often married, exhibited more educational incongruity with their spouses and had fewer children than the control population. Twelve of the 64 women who died suddenly of heart disease and none of the control women had a definite history of psychiatric treatment. The women who died suddenly also smoked more cigarette and consumed greater quantities of alcoholic beverages than age-matched neighborhood control women. Multiple regression analysis revealed that history of psychiatric illness, cigarette smoking, alcohol consumption, educational incongruity and number of children contributed significantly to differences between women who died suddenly of heart disease and control subjects.


Pathology of the heart in sudden cardiac death.

Clinical and pathologic changes in 87 patients who could not be resuscitated from an episode of sudden cardiovascular collapse are described and compared with observations from patients in the same community who were successfully resuscitated from ventricular fibrillation. Findings in patients who died suddenly generally did not differ when the patients were groups by electrocardiographic rhythm on arrival of the mobile coronary aid unit. The pathologic changes of acute thrombosis and recent myocardial infarction did not occur with sufficient frequency in the entire group to be considered causally related to the sudden collapse, occurring in 10 and 5 percent of cases, respectively. Although most patients had evidence of obstructive coronary disease and old myocardial infarction, 8 percent had no significant vascular disease, acute thrombosis, myocarditis or valve disease that might be implicated as a factor in sudden death. There was no relation between age and severity of obstructive coronary disease or frequency of old myocardial infarction in patients who died suddenly. Complete atherosclerotic occlusion in one or more coronary vessels occurred in 51 of 87 (59 percent) and old myocardial infarction in 48 of 87 (55 percent). Although the mean age of this autopsy population was similar to that of all patients in the community who have had ventricular fibrillation on arrival of the aid unit, the nonsurvivors had a greater incidence of myocardial infarction and symptomatic heart disease (73 of 87) than did survivors. Comparison of this autopsy group with persons from the community who were resuscitated from ventricular fibrillation and subsequently had coronary angiograms indicates that the severity of coronary stenosis does not distinguish between survivors and nonsurvivors of an episode of ventricular fibrillation and suggests that other factors influence the outcome of an episode of ventricular fibrillation.


Management of patients with malignant ventricular arrhythmias.

The patient with recurrent malignant ventricular arrhythmias (ventricular fibrillation or ventricular tachycardia with syncope) presents a complex therapeutic problem. To examine this problem, a study was made of 43 consecutive patients with such arrhythmias (mean age 54 years for the 33 men and 43 years for the 10 women). Arrhythmias were not precipitated by either remediable clinical conditions or acute myocardial infarction. The population was divided into two nonrandomized groups based on the type of therapeutic intervention employed. The 26 patients in Group 1 (20 with ventricular fibrillation, 6 with ventricular tachycardia) were subjected to a systematic attempt to select two independently effective antiarrhythmic drugs. Acute drug testing was followed by drug usage over 48 to 72 hours with drug efficacy determined with use of ambulatory monitoring and exercise stress. The 17 patients in Group 2 (10 with ventricular fibrillation, 7 with ventricular tachycardia) received standard antiarrhythmic therapy based on clinical factors and "therapeutic" blood drug concentrations. Twenty-four of 26 patients in Group 1 (92 percent) demonstrated control of arrhythmias and are alive at a mean follow-up period of 17 months. Of 121 drug tests, 47 (39 percent) were effective, 58 (48 percent) were ineffective and 16 (13 percent) provoked major adverse effects. The most effective combination of drugs involved a beta adrenergic blocking agent, a cardiac glycoside and quinidine. Ten of 17 patients in Group 2 (59 percent) have died after a mean follow-up period of 14.8 months. Elements of a successful management program are outlined.


Canine exocrine pancreatic secretory changes induced by an intragastric ethanol test meal.

In five dogs with chronic gastric fistulas (Thomas cannula) and a new type of chronic pancreatic fistula which permits collection of pure nonactivated pancreatic juice after ingestion of a test meal, the following series of experiments were performed: In the first series, a test meal (400 gm. canned dog meat) was given with 200 ml. saline simultaneously infused through the gastric cannula. In response to this stimulus, the 20-minute peak pancreatic flow rate and bicarbonate output were respectively 33% and 34%, of the maximal secretion of the pancreatic gland obtained with secretin in six control dogs provided with gastric and the classical Thomas duodenal fistula. The 20-minute peak protein output represented 84% of the maximal secretory capacity attained with dose-response curves to CCK in the same group of control animals. In the second series either 1.5 or 2.0 gm./kg. ethanol were given instead of saline. Intragastric ethanol induced a dissociation of pancreatic secretion: a significant inhibition of flow rate, of bicarbonate concentration and output and a significant rise of protein concentration; protein output remaining unchanged. It is postulated that ethanol, acting on the stomach and duodenojejunum, evokes, independently of its gastrin-releasing capacity, and unknown humoral or nervous mechanism that counteracts the ethanol-elicited cholinergic-mediated inhibition of pancreatic protein secretion which has been previously described.


Ischemic colitis and malignant atrophic papulosis.

A 37-year old male with a history of idiopathic nephrotic syndrome, hypertension, severe headaches and transient ischemic attacks developed ischemic colitis with stricture formation of the spelnic flexure. Eschemic changes were secondary to vascular lesions involving the middle colic artery and mulitple smaller arteries and arterioles. The vascular lesion is localized to the intimal layer with proliferation of spindle-shaped cells indentical to the gastrointestinal lesion of malignant atrophic papulosis (Degos' disease). The patient had no skin biopsy, or history of skin lesions. This case represents ischemic colitis in a patient with malignant atrophic papulosis with either absent or unrecognized skin lesions.


Correlations of incidence rates for selected cancers in the nine areas of the Third National Cancer Survey.

Incidence date from the Third National Cancer Survey were used to study geographic variation in the occurrence of nine common cancers of nonsexual sites and five sexual sites. It was hypothesized that cancers which varied together across the nine survey communities might have common etiologic factors. The variation was measured by a series of rank and product-moment correlation coefficients in order to summarize the association between pairs of cancers in white males and in white females. The most notable findings were the high correlations between the incidence rates for the three gastrointestinal sites (stomach, colon, and rectum) and bladder cancer in both men and women and the high correlation between three female sexual sites (breast, corpus, and ovary). These two clusters are also correlated with one another. A number of other substantial correlations between pairs of cancers were observed and discussed. These associations suggest possible common etiologic agents, despite the fact that the individual secular trends for some of these cancers differ.


Breast cancer and fertility trends in Canada.

The age-standardized breast cancer mortality rate for Canadian females increased only slightly during the period 1941-1971. In contrast, the age-standardized breast cancer incidence rate for Saskatchewan females more than doubled during the same period. In the interval 1954-1973 there were significant increases in the age-specific mortality rates for females 50-64 years old and in the age-specific incidence rates for five of the six age groups in the 45 to 74 year range. Breast cancer mortality rates during 1970-1972 varied considerably by province. Age-specific rates in the 30-69 year range were significantly and negatively correlated with the proportions by province of married women first married at age 15-19. In Canada and Saskatchewan, respectively, the age-specific breast cancer mortality and incidence rates for females 40-59 years old were significantly and negatively correlated with cohort fertility rates at age 20-24. These data support the hypothesis that early pregnancy protects against breast cancer. The sharp decline in fertility rates since 1960 may result in an increased incidence of breast cancer in the future.


Blood pressure in Seventh-day Adventist vegetarians.

The blood pressures (BP) in 418 vegetarian Seventh-day Adventist (SDA) volunteers in Western Australia were compared with those in 290 non-vegetarian volunteers in Narrogin, a Western Australian country town. The mean systolic and diastolic BPs in the SDAs, adjusted for age, sex, height and weight (128.7/76.2 mm of mercury) were significantly less than those in the Narrogin residents (139.3/84.5). It appeared unlikely that these differences could be explained by differences in alcohol, tobacco, tea, coffee or egg consumption, socioeconomic status or physical activity. There was, however, a gradient toward increasing BP with increasing egg intake in SDAs, and SDAs who drank tea or coffee had a higher mean diastolic BP than those who did not (mean difference of 4.2 mm of mercury). The possibility that selective bias or unmeasured environmental differences might explain the difference in BP between the two groups is discussed.


Tick-borne relapsing fever: an interstate outbreak originating at Grand Canyon National Park.

During the 1973 summer season, 27 employees and 35 overnight guests at the North Rim, Grand Canyon National Park, Arizona, acquired febrile illnesses compatibel with relapsing fever. Sixteen cases were confirmed by finding Borrelia spirochetes in peripheral blood smears or inoculated Swiss mice. Retrospective surveys of 278 employees and 7247 guests at the park revealed that acquisition of illness was significantly associated with the persons sleeping in rustic log cabins and acquiring bites of "unknown" insects. From rodent nesting materials found in the walls and attics of cabins where cases had occurred, infective Ornithodoros hermsi ticks were recovered. Exceptional activity of ticks in human populations appeared to have resulted from a decreased population of the ticks' usual rodent hosts. Vector control activities consisted of spraying the cabins with residual insecticide, removing nesting materials, and "rodent proofing." This outbreak, the largest yet identified in North America, extends the known range of a principal vector and establishes the North Rim as an endemic source of tick-borne relapsing fever.


Bias due to misclassification in the estimation of relative risk.

Lack of bias in the estimation of relative effect in epidemiologic studies depends on the internal validity of the study. This paper conveys in graphic and tabular form the direction and magnitude of bias due to misclassification of study subjects. A series of computer-generated graphs shows that the departure of the estimate of effect (relative risk or odds ratio) from its true value is a function of sensitivity and specificity (measures of classification validity), disease frequency, and exposure frequency. The discussion of bias emphasizes misclassification of the "outcome" variable; i.e., disease occurrence in a cohort study and exposure rate in a case-control study. Examples are used to illustrate that the magnitude of the bias can be large under circumstances which occur readily in epidemiologic research. When misclassification is equal for the two compared groups, the estimate is biased toward the null value, and in some instances beyond; when differential misclassification occurs (as in selective recall in case-control studies) the bias can be in either direction, and may be great. Formulas are derived to estimate the underlying true value of the relative risk or odds ratio using the investigator's observations together with the estimated sensitivity and specificity of the classification procedure.


Pharmacist as applied pharmocologist in association with a pediatric clinical pharmacologist.

The ability of a pharmacist to act as an applied pharmacologist and assist the pediatric clinical pharmacologist in providing influential drug information to attending pediatricians was studied. One hundred consecutive admissions to a pediatric unit of a university hospital were studied. The pharmacist, acting as a member of the department of pharmacology, attended ward rounds and closely followed patient therapy. He attempted to provide all information requested by the attending team of pediatricians and identify all problems in therapy without involving the pharmacologist. Regular meetings were held with the clinical pharmacologist in which the pharmacist made patient presentations and sought assistance in answering those requests for which he had been unable to provide sufficient information. The information provided by the pharmacist during the patient presentations was judged adequate for the clinical pharmacologist's evaluation of patient therapy 96% of the time. The pharmacist successfully answered 81% of the information requests and made 88% of the recommendations directed at change in therapy without involving the pharmacologist. It was concluded that the pharmacist performed successfully as an applied pharmacologist in this study.


Inservice pharmacy technician training program.

The development and implementation of a two-month inservice training program for hospital pharmacy supportive personnel is discussed. A task-oriented approach was used to define the instructional objectives of the program. To emphasize the job-related nature of the instruction, conferences and workshops were selected as the primary teaching methods. A specific instructional plan was designed for drug conferences, giving the trainee an active role in the learning of drug names and dosage forms. On-the-job experience, comprising 30% of the training time, gradually was incorporated into the program. Staff pharmacists and supervisors assumed the teaching responsibilities. During weekly evaluation sessions with each trainee, the coodinator discussed the trainee's performance, pin-pointed deficiencies and suggested means of improvement. The benefits of the program, in terms of selection and sequence of instructional programs, student assessment and program evaluation, are discussed.


Pharmacokinetics in drug therapy II: Applications of clinical pharmacokinetics in the assessment of theophylline therapy.

A patient case is presented to illustrate a systematic approach to the assessment and modification of theophylline therapy by the pharmacist using serum level analysis. The pharmacist is a pulmonary disease service is responsible for: (1) determining relevant aspects of the patient's clinical condition; (2) defining an initial theophylline administration regimen, including route, dose and schedule; (3) estimating expected theophylline levels based upon the regimen and known or assumed parameters of theophylline in the patient; (4) defining and recommending number and timing of serum samples to be drawn for analysis; (5) obtaining laboratory results and comparing with preliminary estimations; (6) assessing clinical response or toxicity, or both; and (7) recommending appropriate modifications in the theophylline regimen.


The conduction system in cardiac amyloidosis. Clinical and pathologic features of 23 patients.

Cardiac amyliodosis is frequently associated with major electrocardiographic conduction disturbances; but that these disturbances are due to infiltrative destruction of the conduction system by amyloid is unclear. We studied the conduction systems in 23 autopsy patients with cardiac amyloidosis (group 1) (mild in seven, moderate in five and severe in 11), 21 (91 per cent) of whom had had abnormalities of conduction or rhythm during life. For comparison, we examined the conduction system in 23 control subjects matched in age and heart weight (group 2). Of the 23 patients in group 1, only three had extensive amyloidosis of the conduction system; in all three, electrocardiograms showed first degree atrioventricular block and left anterior hemiblock. A more common morphologic abnormality of the conduction system was severe sinoatrial node fibrosis present in seven (30 per cent) patients, and idiopathic atrophy and fibrosis of the bundle branches present in six (26 per cent) patients. None of the patients in group 2 had severe sinoatrial node fibrosis, but two (9 per cent) had idiopathic atrophy and fibrosis of the left bundle branch. Marked fibrosis of the sinus node was more frequent in patients with severe or moderate amyloid, but fibrosis of the bundle branch did not appear to be related to the amount of amyloid elsewhere in the heart. Varying degrees of atrioventricular and bundle branch block were also present in six patients with no morphologic abnormalities of the conduction system. Thus, conduction and rhythm disturbances are frequent in cardiac amyloidosis, but direct amyloid infiltration of the specialized conduction tissue of the heart does not account for the majority of these disturbances. Whether the increased incidence of fibrosis of the conduction system in group 1 compared to that in group 2 relates to the infiltrative myocardiopathy is uncertain.


Appearance of circulating DNA during hemodialysis.

The appearance of circulating DNA during hemodialysis was investigated by use of a modified counterimmunoelectrophoresis assay capable of detecting as little as 0.02 to 0.05 microng of native DNA per milliliter of plasma. It was found that free DNA was regularly released during procedure in widely varying amounts which ranged as high as 5 microng/ml. Both the amount of plasma DNA and its rate of appearance increased progressively throughout the procedure and had no temporal correlation with the transitory early leukopenia that was previously described. Circulation in vitro of fresh blood through a dialysis coil also resulted in the appearance of plasma DNA suggesting that passage of blood through the coil itself can account, at least in part, for circulating DNA, presumably by release from leukocytes. Neither the presence (nor reversal) of the uremic state per se nor removal of inhibitors of the assay during hemodialysis are able to account for the findings. Whether free circulating DNA is of clinical importance is, as yet, unknown. A hypothesis is proposed linking chronic exposure to circulating intracellular materials, including DNA, to the accelerated atherosclerosis recently described as a late complication of hemodialysis. Currently, hemodialysis is the only clinical state known to be characterized by the presence of circulating DNA over long periods of time. Since this phenomenon is iatrogenically induced, further exploration of possible pathogenetic implications seems particularly important.


Family studies in patients with primary parathyroid hyperplasia.

The relatives of 25 index patients with primary parathyroid hyperplasia were tested for hypercalcemia. At least 13 of these patients had one or more first degree relatives with hypercalcemia. Two familial syndromes each with autosomal dominant transmission were recognized. Two index patients were part of large kindreds categorized as having familial hypocalciuric hypercalcemia (FHH). Manifestations of multiple endocrine neoplasia type I were present in the kindreds of at least four other index patients (FMEN I). In seven other kindreds there were too few affected members to allow definitive classification. Differences between manifestations of FHH and FMEN I were described. Among offspring of affected persons in kindreds with FHH, as distinct from FMEN I, the prevalence of hypercalcemia approached the theoretic maximum of 50 per cent during the first two decades. In FHH, nephrolithiasis and peptic disease were unusual; moderate hypercalcemia occurred without hypercalciuria; and subtotal parathyroidectomy did not abolish hypercalcemia. Concentrations of peptide hormones other than parathyroid hormone (PTH) were normal in those with FHH; in FMEN I high concentrations of glucagon in plasma were found in five of six patients tested, and high concentrations of gastrin were found in three of 12 patients. Hypergastrinemia generally accompanied obvious peptic disease. Distinction of the two conditions is important since patients with FHH may not benefit from subtotal parathyroidectomy, but they generally have a better clinical prognosis than do patients with FMEN I.


Bacteremia and fungemia complicating neoplastic disease. A study of 364 cases.

During a 14 month period there were 364 episodes of bacteremia and fungemia at Memorial Sloan-Kettering Cancer Center. The first nine months of the study were retrospective, and the next five prospective. In patients with leukemia or lymphoma (group 1), Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus were the most frequently isolated organisms. The mortality in this group was 40.5 per cent. In the patients with solid tumor (group 2), Esch. coli, Staph. aureus, Bacteroides sp. and Candida sp. were most frequent. Mortality was 27.8 per cent. The source of infection in both groups was often indeterminate. High mortality was associated with pulmonary and intraabdominal infection and with Ps. aeruginosa, K. pneumoniae or polymicrobic sepsis. Factors of prognostic significance were the causative microorganism, source of infection and shock. Although mortality was higher in patients with leukopenia than in those with normal leukocyte counts, the differences were not significant. The mortality in this series was low considering the severity of the underlying diseases and the immunosuppressed state of many of the patients. In a prospective, randomly controlled study, mortality was further diminished by infectious disease consultation at the time the positive blood culture was reported. Severe fungal superinfection, predominantly aspergillosis and candidiasis, was found in 52 per cent of the autopsy patients with leukemia or lymphoma (group 1), but in only 8 per cent of those with solid tumors (group 2).


Concurrent hypercortisolism and hypermineralocorticoidism.

Hypertension and hypokalemia occur in patients with Cushing's syndrome whereas aldosterone production is normal and plasma renin activity is usually normal or increased. A normal aldosterone level in the face of suppressed plasma renin activity is unusual and suggests excess mineralocorticoid hormone activity. Our patient, who had Cushing's syndrome due to adrenocortical adenoma, can be classified as having low renin hypertension (suppressed renin and normal aldosterone levels). The mineralocorticoid hormone in excess was deoxycorticosterone which suppressed renin. The aldosterone production was normal and was produced solely by the adenoma. Contralateral adrenal gland suppression of both the zona glomerulosa by deoxycorticosterone via renin, and of the fasciculata by cortisol via ACTH was demonstrated after removal of the adenoma. Normal adrenal function was gradually restored.


A comparative study of CLEP scores between MT and MLT students.

CLEP subject examinations for the areas of clinical chemistry, microbiology, hematology and immunohematology were administered to medical technology (MT) and medical laboratory technician (MLT) students. Test scores were analyzed and showed that MT students scored from 25% to 48% higher than MLT students. Mean percentile ranks were compared with college courses completed; these indicated that additional upper division academic courses raised the mean percentile rank. Results indicate that the Microbiology Category Examination evaluates general microbiology rather than clinical microbiology. Data in this study support the use of the CLEP examinations to measure cognitive knowledge of MLTs for upward mobility, thereby eliminating duplication of course content.


Sensitivity of cold hemagglutination testing as a function of red cell age.

It has been suggested that freshly obtained red cells fail to agglutinate in the presence of antibody, and that the same cells left for several days at 4C in anticoagulant will usually be agglutinated by the same antibody, erythrocyte stabilization being responsible for this differential effectiveness of agglutination. Since supportive documentation for this assumption is not available, and since the concept of differential effectiveness of agglutination as a function of red cell age may be of great significance to the sensitivity of laboratory procedures which take advantage of antigen/antibody reactions, the above hypothesis was investigated using a cold agglutination procedure as a test system. Cold hemagglutination was chosen for reasons of expediency. Results of that investigation, possible explanations for the original hypothesis, and suggestions for further testing are presented here.


A comparison of diagnostic and certifying examinations.

Testing and measurement represent a critical component of an educational system since they provide the essential information for making fundamental educational decisions. The type of information required in a particular situation determines how one should conceive, develop, and evaluate the measurement device. This paper compares certifying exams used to determine a person's overall level of competence, and diagnostic exams used to determine a profile of a person's strengths and weaknesses in a particular area. These two types of exams are discussed in terms of their associated educational problem, types of decisions required, optimal test development procedures, and appropriate forms of reliability and validity.


The association of maternal and neonatal thrombocytopenia in high-risk pregnancies.

In this study of 136 women with pre-eclampsia, eclampsia, placenta previa, or abruptio placentae, 21 mothers were noted to have thrombocytopenia. Seventeen of the 21 were in the pre-eclampsia group. Of the 21 thrombocytopenic mothers, nine were associated with thrombocytopenia in the children, seven children had normal platelet counts, and five had no counts performed. Eight of the nine thrombocytopenic neonates were associated with pre-eclampsia in the mother, and five of these were not believed to have disseminated intravascular coagulation as the etiology of the platelet defect. The results suggest that thrombocytopenia is common in high-risk pregnancies in both the mother and the baby. However, the etiology of the platelet defect cannot be easily explained on the basis of a hypercoagulable state.


Ultrasound as an aid in intrauterine transfusion.

Although the number of patients with Rh isoimmunization in pregnancy has been decreasing in recent years, intrauterine transfusion is still an important form of therapy for those patients whose infants have erythroblastosis. We have used both gray-scale and real-time ultrasonography for the last ten cases in which intrauterine transfusion was necessary. These techniques were used in preference to fluoroscopy and x-ray control to identify the placental site and fetal abdomen and to direct the insertion and placement of the transfusion needle. We were able to visualize the needle when it entered the amniotic cavity and the fetal abdomen. The technique afforded continuous visualization and a cross-sectional image of the fetus, steps which increase the efficiency and safety of the procedure and decrease radiation to the fetus.


The effect of progesterone on estrogen-induced uterine blood flow.

The effect of progesterone on estrogen-induced uterine blood flow was investigated in repeated experiments in seven nonpregnant, oophorectomized ewes with chronically implanted electromagnetic flow probes and catheters inserted into branches of the uterine arteries. Administered alone, progesterone has no effect on base-line uterine blood flow. Following intramuscular injection of progesterone (3 to 5 mg-per kilogram of body weight), peak uterine blood flow responses to 1 microng of estradiol-17beta were suppressed by 25 per cent compared to those of control animals. Direct intra-arterial infusion of progesterone, at concentrations sufficient to reproduce uterine venous levels observed in late pregnancy in the sheep, inhibited estrogen-induced uterine blood flow by 20 per cent. The findings support the hypothesis that progesterone modulates the estrogen-induced flow responses in both the pregnant and nonpregnant uterine vascular bed.


Erythrocytic microcytosis: clinical implications in 100 patients.

Hematology results from 3800 blood samples were examined for the presence of erythrocytic microcytosis. One hundred patients with electronically measured mean corpuscular volumes of 75 cubic microns or less were reviewed to determine the cause of microcytosis and evaluate recently described simplified techniques for separating thalassemia trait from other causes of microcytosis. The discriminant function formula of England and Fraser [MCV - RBC - (5 x Hgb) - 3.4] was found to be useful in uncomplicated patients with the Mediterranean type of thalassemia trait (betadegree) but less useful in the African type (beta+) of heterozygous beta-thalassemia. Anemias of chronic disorders were found to be a major cause of microcytosis. Microcytosis of no apparent cause was found in some children. Improved techniques in hemoglobin A2 quantification remain the best approach for detecting beta-thalassemia heterozygotes.


The relationship of mammary temperature to parturition in human subjects.

Four hundred and seventy thermography studies were performed on 210 women to measure mammary temperature prior to, during, and immediately following pregnancy. Mean mammary temperature of 33.3 +/- 0.1 degrees C. (S.E.M.) obtained in 14 nonpregnant patients increased to 34.2 +/- 0.1 C. (S.E.M.) by nine weeks of gestation (p less than 0.01). The difference between mammary and sternal temperature was negative in the nonpregnant state and became positive after 18 weeks of pregnancy. Mammary temperature remained significantly higher in the pregnant group than in the nonpregnant group (p less than 0.001) up to term. In six postpartum patients, a further increase from prepartum values to 35.4 +/- 0.6 degrees C. (S.E.M.) occurred. The results suggest that relatively large changes in mammary blood flow and/or metabolic rate take place in human subjects in early pregnancy and on the day following parturition.


Subspecialization in obstetrics and gynecology.

The formal development of subspecialities with obstetrics and gynecology has focused attention on problems of physician supply and demand. The need for subspecalized practitioners appears to be 750 in maternal-fetal medicine and 350 each in reproductive endocrinology and gynecologic oncology. Taken together, this number represents about 10 per cent of presently certified specialists. As supply is now developing, the demand in gynecologic oncology should soon be saturated, but there will be a longer term demand in maternal-fetal medicine and in reproductive endocrinology. However, the expectation of 30 per cent of present residents that they will enter subspecialities is far in excess of available fellowships or ultimate need. Fellowships leading to subspecialty certification should be approved by the Residency Review Committee, and numbers should be limited to best estimate of need.


The relationship between bone marrow sideroblasts and iron deficiency in chronically hemodialyzed uremic subjects.

Bone marrow sideroblast counts were found to be persistently depressed to between 0 and 30 per cent in 24 uremic patients with residual renal tissue undergoing chronic dialysis therapy. Marrow sideroblastopenia notwithstanding, sideroblast counts in these subjects correlated well with iron balance, being respectively 6.6 +/- 0.8 (S.E.M.) per cent in iron depleted, and 18.2 +/- 1.7 per cent in iron-repleted individuals (p less than 0.0005). Following bilateral nephrectomy a persistent relative marrow sideroblastosis developed, counts reaching values of 46.5 +/- 3.1 per cent on average. It is suggested that this sideroblastosis is a response to reduced heme synthesis and reflects the iron removal function of ferritin granules within erythroid cells.