Influence of blood pressure changes with and without proteinuria upon outcome of pregnancy. A prospective study of 10,074 white gravidas and 2,880 black gravidas carried out during the years 1959 to 1967 has been analyzed with respect to the impact of elevated blood pressures and/or proteinuria upon pregnancy outcome. Edema was not considered because no evidence is available to indicate that its occurrence increases risk. The mean arterial pressure exhibited during the fifth and sixth months of pregnancy was found to be of significance, as well as the absolute levels of blood pressure attained prior to labor and delivery. The degree of rise in blood pressure was not of importance in itself. However, categories with significant proteinuria had greater increases in mean arterial pressure than did comparable categories without it. Significant proteinuria alone but especially with hypertension was also detrimental to pregnancy outcome. Eight categories incorporating early and late hypertension with and without proteinuria were created, and these were given descriptive diagnostic labels. Only "gestational hypertension," as defined, proved to be essentially devoid of risk to the fetus. In all other non-normotensive categories there was an increase in the stillbirth rate, the perinatal mortality rate, the frequency of intrauterine growth retardation, and neonatal morbidity. In every category, each of these untoward events was greater in black than in white gravidas, and a higher percentage of blacks was noted in each of the hypertensive categories. It is believed that hypertension, significant proteinuria, or both are associated with decreased uteroplacental blood flow which is the common denominator for all of these deleterious effects. The study suggests that "gestational hypertension" occurring late but without proteinuria may or may not represent an early stage of "pre-eclampsia" but does not, at least, place the infant at any substantially increased risk.


The prognostic and diagnostic value of total estriol in urine and in serum and of human placental lactogen hormone in serum in the last part of pregnancy. The benefit to the antenatal care from using estriol and human placental lactogen (hPL) determinations is emphasized and likewise that special attention must be paid to values below the reference intervals. Referring to biosynthesis and place of production, a survey is given of the various causes of low estriol and/or low hPL values, and a number of clinical cases illustrate the matter. A follow-up study of children from pregnancies with low estriol values has disclosed an alarming number of cases of severe handicaps.


Renal disease in pregnancy.

Renal disease in pregnancy. Renal biopsy was obtained in 11 primiparous and 9 multiparous patients with severe pre-eclampsia. The large number of patients with renal disease allowed for single-case evaluation. Eclamptic convulsions and fetal deaths were observed in association with renal disease without foci of additional primary glomerular endotheliosis. The data indicate that pregnancy can exacerbate renal disease and allow for early diagnosis. Fluorescence angiography revealed changes in patients in whom the optic fundi were normal. Tissues of glomerulonephritis stained by immune fluorescence against immunoglobulins and on occasion against human fibrinogen. Primary endotheliosis and nephrosclerosis stained against fibrinogen only. There was no pattern of laboratory data to make the differential diagnosis between primary endotheliosis and various forms of renal disease. Fibrinogen breakdown products were inconsistently increased in contrast to fibrin monomer formation, which was increased regardless of the underlying morphology. It is our feeling that renal biopsy with subsequent pathologic classification is the only technique we have at present which provides relevant information on the effect of renal disease on pregnancy and vice versa.


Interaction of progesterone and adrenocorticoids in ultrastructural development of the mammary gland of the cat. Comparative development of rough endoplasmic reticulum (RER) in mammary glands of rats was studied in relation to levels of progesterone and adrenocorticosteroids. The tranquilizer perphenazine was administered to stimulate secretion of prolactin; serum glucocorticoids also increased. When perphenazine was administered after ovulation, serum progesterone was increased 18-fold, but when treatment was begun on proestrus, ovulation was inhibited and serum progesterone increased only 4-fold. Concentrations of progesterone in the breast were approximately 10-fold greater than, but parallel to, serum concentrations. In ovulating rats the RER was poorly developed. In nonovulating rats extensive development of RER occurred. Cortisol acetate given to ovulating, perphenazine-treated rats did not alter levels of serum progesterone, but tissue progesterone was reduced by 50 per cent and development of RER approached that in nonovulating rats. The development of secretory capacity (formation of RER) in the breast appears to depend on the relation between stimulation by glucocorticoid and inhibition by progesterone.


Urinary amine alterations in drug-addiction pregnancy. Urinary amines were measured in 122 drug-addiction pregnancies. The profile of the patient indicates that 86 per cent were black and had a total of 2.98 pregnancies and 1.97 living children. She made 5.4 prenatal visits to our special drug-abuse prenatal clinic. The 208 antepartum 24 hour urine determinations indicated a mean excretion of epinephrine to be 28 +/- 1.6 mug which rises to 60 mug on the first day post partum. These values indicate increased adrenal gland activity and are more than six times greater than seen in normal pregnancy. The antepartum mean 24 hour urine excretion of norepinephrine is 49.7 +/- 2.6 mug which does not change on the first postpartum day. The antepartum norepinephrine values are 50 per cent higher than seen in normal pregnancy. Drug-addiction pregnancy in patients who are well controlled on methadone have markedly increased adrenal gland activity as evidence by increased levels of epinephrine. The sympathetic nervous system activity as evidenced by urinary norepinephrine is only slightly increased. Drug addiction alters the normal homeostatic mechanisms of pregnancy.


The mechanism of midtrimester abortion induced by intra-amniotic instillation of hypertonic saline: a modification of Gustavii's lysosomal hypothesis. This modification of Gustavii's hypothesis recognizes the central role of saline-induced decidual cell necrosis and secondary prostaglandin release in the initiation of myometrial activity. In the absence of significant necrosis in the decidua basalis, passive stretching of the subplacental myometrium is considered to activate this region leading to secondary intervillous stasis and the reduction in progesterone delivery to the myometrium and systemic circulation. This drop in progesterone further sensitizes the myometrium to PGF2alpha stimulation and helps the self-sustaining process of myometrial activity culminating in clinical abortion. A third hypothetical contributing factor may be the loss of some myometrial inhibitor normally present in the amniotic fluid.


Acute effects of maternal ethanol infusion on fetal cardiac performance. In adult animals and man, both acute and chronic ethanol intake is associated with depression of myocardial performance. Accordingly, the cardiac effects of maternal ethanol infusions, in a manner comparable to common obstetric practice of inhibition of premature labor with ethano mighte for inhibition of premature labor, were evaluated in six chronically instrumented fetal sheep. Fetal and ewe arterial PO2, PCO2, and pH values remained within normal limits with infusion rates of 15 c.c. per kilogram of 10 per cent ethanol over two hours (blood ethanol = 110 mg. per cent) and 15 c.c. per kilogram over one hour (blood ethanol = 210 mg. per cent). Fetal instrument evaluation (for 14 to 30 days after operation) provided data concerning pressures and cardiac dimensions which allowed analysis of left ventricular performance. Ethanol produced a significant depression of the extent (p less than 0.01) and velocity (p less than 0.001) of left ventricular myocardial fiber shortening as well as in the mean rate of left ventricular myocardial fiber shortening as well as in the mean rate of left ventricular circumferential fiber shortening (p less than 0.01). These indices of cardiac contractility were depressed in the absence of changes in end diastolic diameter, left atrial pressure, and systemic arterial pressure. Thus, the practice of inhibition of premature labor with ethano6 might contribute to depressed myocardial performance in the neonatal period.


Factors affecting intrauterine contraceptive device performance. I. Endometrial cavity length. The relationship of endometrial cavity length to intrauterine contraceptive device (IUD) performance was evaluated in 319 patients wearing three types of devices. The rate of events, defined as pregnancy, expulsion, or medical removal, increased significantly when the length of the IUD was equal to, exceeded, or was shorter by two or more centimeters than the length of the endometrial cavity. Total uterine length was found to be a less accurate prognostic indicator of IUD performance than endometrial cavity length alone.


Metabolism of oral contraceptive drugs. The formation and disappearance of metabolites of norethindrone and mestranol after intravenous and oral administration. Previous studies from this laboratory reported that 3H-labeled metabolites with half-lives of more than 24 hours may remain in the plasmaa of women receiving an intravenous injection of 3H norethindrone or 3H mestranol. To confirm the presence of these metabolites, blood samples were collected for five days after injection of 3H norethindrone or 3H mestranol; 3H representing metabolites of norethindrone disappeared with half-life values of 42 to 84 hours (mean 67 hours), while 3H representing metabolites of mestranol declined with an average half-life of 45 hours (range 37 to 65 hours). When the 3H-labeled drugs were administered orally, metabolites of similar half-life were formed. Because these compounds exist for several days after a single administration and since oral contraceptive drugs are normally taken daily, the possiblity of the accumulation of 3H in the plasm of women receiving several consecutive doses of 3H norethindrone was investigated. The results of this study show a stepwise accumulation of the 3H metabolites when 3H norethindrone was administered in six daily oral doses. However, the 3H levels declined from the peak on the sixth and last day of the treatment at a rate equivalent to those previously measured after intravenous or oral administration.


Metabolites of meperidine in the fetal and maternal serum. Although meperidine appears to be the safest obstetric analgesic agent, it has been associated with infant respiratory depression in certain situations. It would appear that the incidence of fetal depression related to meperidine is dependent on the time of injection prior to delivery, the quantity of drug administered, and the rate of maternal metabolism of the analgesic. Previous work showed that meperidine is metabolized in the maternal system by one of three patterns. The present study demonstrates that the particular maternal serum pattern is characteristic for the individual, regardless of whether the patient is pregnant or not, and that the fetal depression, although usually mild, can be correlated with fetal pH data as well as Apgar scores. In addition, this study supports indirectly the contention that metabolites of meperidine rather than the parent compound cause fetal depression. It would appear, therefore, that in certain obstetric cases with a higher probability for infant depression, other analgesic agents might be considered, especially if the serum pattern indicates meperidine is being metabolized.


Contraction of a perifoveal epiretinal membrane simulating a macular hole. Four patients observed for a three- to four-year period had a hole in an epiretinal membrane overlying the macula that mimicked a macular hole. In two patients the clinical appearance remained essentially constant. In one, the epiretinal membrane contracted further, reducing the apparent macular hole to a slit and causing the typical appearance of a macular pucker. In the fourth patient, the epiretinal membrane peeled spontaneously causing the apparent hole to disappear. None of the patients had static perimetric findings that suggested a true macular hole. All of the patients had normal or nearly normal visual acuity when first seen. This was maintained except in the patient who suffered further membrane contraction. Fluorescein angiography demonstrated a slight fluorescence in the base of the hole in three of the four patients; however, it was not as pronounced as one sees in true macular holes. Lamellar macular holes characteristically show no fluorescence in the area of the hole.


Carbon monoxide retinopathy.

Carbon monoxide retinopathy. A 26-year-old man who had become comatose after having inhaled carbon monoxide developed retinal venous engorgement and peripillary hemorrhages. Retinal changes closely resembled those that accompany hypoxemia.


Recurrent amyloid involvement in the virreous body after vitrectomy. A patient with vitreous opacification due to primary familial amyloidosis underwent bilateral vitrectomy via the pars plana with excellent visual results. Two and one half years later opacification of the vitreous body recurred in the retrolental area bilaterally, necessitating a repeat vitrectomy in the left eye. This opacity was successfully removed from the posterior surface of the lens without apparent damage to the lens.


A histologic survey of trabeculectomy.

A histologic survey of trabeculectomy. Thirty-two tissue blocks removed during trabeculectomy were examined histologically, 16 by both scanning electron microscopy and light microscopy, and 16 by light microscopy alone. Trabecular meshwork was identified in 27 specimens (84.3%) and Schlemm's canal in 17 (53%), each found with equal frequency by either technique. Ciliary muscle was identified in eight of 32 of specimens (25%) examined by light microscopy, but was present in 12 of 16 specimens (75%) examined by scanning electron microscopy. The identification of these specific anatomical structures did not correlate with the postoperative outcome. These findings support the contention that trabeculectomy is a filtering procedure.


Changes in the facility of aqueous outflow induced by lens depression and intraocular pressure in excised human eyes. The effects of intraocular pressure on aqueous outflow facility and mechanical tension on the iridocorneal angle were evaluated in 44 excised postmortem human eyes. Mechanical tension on the iridocorneal angle was induced by depression of the crystalline lens posteriorly in a quantitative manner to simulate the effect of cyclotonia on the facility of aqueout outflow. In eyes perfused at constant intraocular pressure but with stepwise increases in lens depression, the increase in facility of outflow produced by the increased tension on the iridocorneal angle was minimal at low levels of intraocular pressure (2.5 and 5 mm Hg) and greatest at higher levels of intraocular pressure (10 to 25 mm Hg). Conversely, in pairs of eyes perfused over a graded series of increasing intraocular pressure, and subjected to maximal lens depression, facility of outflow remained constant until intraocular pressure exceeded 20 mm Hg; in the fellow eyes, perfused without lens depression, facility of outflow diminished linearly with increasing intraocular pressure.


Ocular enucleation in a patient with severe classic hemophilia A. A 27-year-old man with severe classic hemophilia A (antihemophilic globulin level: 1.5% of normal) had blunt trauma to his left eye that produced a corneoscleral laceration with prolapse of the intraocular contents. His left eye was enucleated under management with factor VIII replacement. This consisted of sufficient cryoprecipitate to increase the calculated circulating factor VIII level to 125%, sufficient factor VIII every 12 hours to increase peak postinfusion levels from 100 to 120%, and to maintain minimum levels of 30% immediately before infusion. Because he had developed a gingival hematoma when he was placed on epsilon amino caproic acid after only one day of factor VIII replacement following extraction of mandibular molars, we continued the high level of factor VIII replacement for five days and then began antifibrinolytic epsilon amino caproic acid therapy. His surgical and postoperative course were uneventful on this regimen.


Plasma cell content of main and accessory lacrimal glands and conjunctiva. The size, weight, and plasma cell content of main and accessory lacrimal glands were examined and compared to the number of plasma cells in the conjunctiva. There were from four to 35 accessory lacrimal glands in the upper conjunctiva and a rare accessory gland in the lower conjunctiva. The total accessory gland mass was approximately one tenth of the lacrimal gland mass although the number of plasma cells was approximately 1/20 of the mass. The number of plasma-cells in the lacrimal gland was estimated to be 3,200,000; in the conjunctiva, 2,100,000; and for the accessory glands, 180,000. Because of the many plasma cells in the relatively inaccessible lacrimal gland, cells of the lymphatic series may home to the lacrimal gland by non-antigenic mechanisms.


Cryotherapy of basal cell carcinoma in oculoplastic surgery. Cryotherapy was an effective modality in the treatment of basal cell carcinoma in the eyelid and periorbital area and cured 93% of the 29 lesions in 25 patients. This method was especially advantageous in patients with blood clotting disorders; those with medical contraindications to, or who refused, classical surgery; patients who had prior radiation or surgery; patients with the basal cell nevus syndrome or xeroderma pigmentosa; and in patients with medial canthal tumors. Experimental cryotherapy in the albino rabbit showed their lacrimal system is not adversely affected by freezing in the temperature range required for tumor death.


Isolated retinal arterial aneurysms.

Isolated retinal arterial aneurysms. We observed three patients with isolated retinal arterial aneurysms and obtained a clinicopathologic correlation in one of them. All three were hypertensive and in the sixth or seventh decade of life. Fatty exudates were present around the aneurysms, taking the form of large circinate rings in two cases. Microscopic examination in one case revealed a retinal arterial aneurysm with an extensive fibroglial reaction around it. Dilated capillaries, hemosiderin deposits, and both lipoidal and proteinaceous exudates were found in the adjacent retina. Isolated retinal arterial aneurysms appear to be distinct clinical entity as compared to miliary aneurysms of the cerebral circulation.


Lymphocyte sensitivity to glucocorticoids. We evaluated the possibility of identifying patients with open-angle glaucoma based on the in vitro behavior of their lymphocytes in the presence of glucocorticoids. Our results do not support the hypothesis that lymphocytes from patients with open-angle glaucoma, as compared to those from normal subjects, are more sensitive to the presence of corticosteroids in vitro. In addition, the degree of inhibition induced by glucocorticoids was closely related to the amount of activation of the lymphocyte membrane induced by different concentrations of phytohemagglutinin. Our results indicated that this may be a general phenomenon rather than one that is specific to a particular ophthalmological condition.


The prognostic value of HLA-B12 and HLA-B7 antigens in patients with increased intraocular pressure. The presence of the histocompatibility antigens HLA-B12 or HLA-B7 in 76 patients with increased intraocular pressure and a GG response to topical corticosteroids (intraocular pressure over 31 mm Hg after six weeks of topical 0.1% dexamethasone eyedrops, four times daily) correlated with the development of glaucomatous visual field loss. In close agreement with prevalences in patients with primary open-angle glaucoma, 14 (88%) of the 16 patients with increased intraocular pressure and a GG response who developed glaucomatous visual field loss had either HLA-B12 or B7 antigens. Fourteen (41%) of 34 patients with increased intraocular pressure and a GG response who had B12 or B7 antigens developed glaucomatous visual field loss but only two (5%) of 42 similar patients without either antigen had visual field loss. Other factors such as the initial intraocular pressure, the horizontal cup/disk ratio, and family history of glaucoma proved less valuable as prognostic indicators in this series.


Choroidoretinal vascular anastomoses after blunt trauma to the eye. Six weeks after blunt ocular trauma in a 38-year-old white man, choroidoretinal vascular anastomoses occurred at the site of choroidal and retinal rupture. Neovascularization was not observed. Anastomoses of this type have been documented in other cicatrizing and granulomatous disease processes.


Pretectal syndrome with metastatic malignant melanoma to the posterior commissure. A 46-year-old man with a known metastatic tumor developed the sudden onset of upgaze paralysis, impaired convergence, eyelid retraction, pupillary light-near dissociation, convergence-retraction nystagmus, and ocular skew deviation in association with subarachnoid hemorrhage. Selective interruption of the posterior commissure by metastatic melanoma provided  a precise anatomic correlation of the pretectal syndrome in man.


The Dirofilaria parasite in the orbit.

The Dirofilaria parasite in the orbit. A 51-year-old white man had proptosis, pain, and inflammation of the left orbit and later developed diplopia. Treatment with antibiotics relieved most of the symptoms but a localized painful mass persisted in the left orbit. On biopsy a Dirofilaria worm was found. The patient was treated with corticosteroids and the residual nodule subsided. The patient was seen regularly for five months after surgery and the lesion has not recurred.


Lacrimal obstruction after migration of orbital floor implant. A 7-year-old girl developed epiphora, recurrent purulent conjunctivitis, and dacryocystitis 32 months after the repair of a traumatic orbital floor fracture. Dacryocystography and surgical exploration revealed that migration of the orbital floor implant had caused obstruction of the nasolacrimal duct at the sac. Migration of the implant was probably due to a failure to anchor the implant properly to bone.


Small-incision capsular fragment forceps. Capsular fragment forceps were designed especially for small-incision microsurgery. The blades were fashioned in a bayonet design so that capsular material may be grasped by the tip of the forceps while iris is not pinched by the heel of the forceps.


Mirror fixation.

Mirror fixation. A mirror is the ideal fixation device for an ophthalmoscopic examination: it is the essense of simplicity, and there is nothing the patient would rather watch than himself.


Suturing forceps for microsurgery.

Suturing forceps for microsurgery. A microsurgical modification of the Rizzuti scleral fixation forceps for corneal and cataract surgery employs Bonn 0.12-mm teeth on an angled handle with an appropriate curve between the teeth to fix the tissue more adequately to allow accurate placement of sutures.


Fluorescein oropharyngoscopy.

Fluorescein oropharyngoscopy. To evaluate patency of the lacrimal system, fluorescein was instilled in the conjunctival cul-de-sac and the posterior oropharynx was examined with ultraviolet light. In 20 normal patients fluorescein was evident in one to 30 minutes. In cases of complete nasolacrimal duct blockage no fluorescein appeared after two hours.


Contact lens and corneal topography with wear of the Soflens. Changes in the topography of the cornea and the contact lens during and after adaptation to Bausch and Lomb Soflenses were measured in 7 eyes by means of keratometry and photoelectric keratoscopy. Generally, little change was found in the central or peripheral surface topography for either the cornea or the contact lens. Where small changes did occur, they were found to be independent of the original corneal curvature, the fit of the lens, or the duration of wear. Significant correlations were found, however, between the additional spectacle lens power (required over the contact lens to restore maximum visual acuity) and the change in curvature of the anterior surface of the Soflens, and betwen the toricity of the front surface of the contact lens and that of the cornea.


Values, personality, physical characteristics, and refractive error. A questionnaire containing: (a) a questionnaire of physical characteristics associated with psychosomatic symptoms, (b) questions to determine the presence of myopia or hypermetropia but not the amount of error, (c) a shortened version of the Gough Adjective Check List, and (d) the Heist and Yonge Omnibus Personality Inventory were administered to 782 introductory psychology students attending Washington State University. This group consisted of 297 self-identified myopes (117 males, 180 females), 439 emmetropes (207 males, 232 females), and 46 hypermetropes (15 males, 31 females). Results indicated that myopes and nonmyopes differed from one another with respect to their value systems, personality, and physical characteristics as assessed by the components of the questionnaire. Differences in these characteristics were consistently found by all assessment techniques to exist most often between myopes and hypermetropes and between emmetropes and hypermetropes rather than between myopes and emmetropes. In general myopes exhibited a personality pattern of introversion, whereas hypermetropes maintained a pattern described as extroverted.


New design principles for visual acuity letter charts. This paper intoduces new principles for the design and use of letter charts for the measurement of visual acuity. It is advocated that the test task should be essentially the same at each size level on the chart. Such standardization of the test task requires the use of letters of equal legibility, the same number of letters on each row, and uniform between-letter and between-row spacing. It is also advocated that, combined with the test task standardization, there should be a logarithmic progression of letter size. Charts incorporating these design features have been made. These charts facilitate the use of nonstandard testing distances which might be used when there is low visual acuity, when examination room layout prevents testing at the standard distance, or when it is necessary to validate visual acuity scores or detect malingering. Adjusting the visual acuity score according to the chosen testing distance is simplified by the use of logarithmic scaling.


Telescopic lenses and driving.

Telescopic lenses and driving. In some states, persons with significantly reduced visual acuity are being licensed to drive while wearing telescopic spectacle lenses (TSL). In order to evaluate possible visual field limitations present with these devices, the peripheral visual fields of a group of normally sighted subjects were measured while they wore TSL. Severely restricted central fields and sizeable ring scotomas were present with all units tested. These result indicate that driving with TSL should be discouraged.


Learning disability: a multifaceted health threat an optometric question. A conceptual model for the natural history of learning disabilities as a health threat will be presented. The model illustrates the multitude of individual and environmental factors influencing the subsequent physical and mental well-being of disabled learners as well as the professional interaction and interdisciplinary cooperation needed to limit if not prevent the societal impact of learning disabilities.


Ultrastructure of human malignant diffuse mesothelioma. Eleven cases of malignant diffuse mesotheliomas, histologically classified into two groups, epithelial (5 pleural and 3 peritoneal) and biphasic or mixed (2 pleural and 1 peritoneal) forms, were stuied by electron microscopy to elucidate their ultrastructural characteristics. The neoplastic cells of the epithelial forms were varied in ultrastructure, from well differentiated (marked by polarity, micovilli, glycogen granules, junctional structures, tonofilaments, intracellular vacuoles, and a basement membrane) to poorly differentiated (which lacked some of these epithelial characteristics). In four of eight instances in epithelial type tumors, nonepithelial or mesenchymal neoplastic cells were recognized. The biphasic or mixed cases included three major cell types: epithelial, atypical epithelial, and mesenchymal. It appeared that there were transitional forms among the three cell types. The observations support the concept that the neoplastic cell of malignant mesothelioma can differentiate into a number of cell lines.


The retinal capillaries of the rat in deoxycorticosterone hypertension. An ultrastructural study with the diffusion tracer lanthanum. Unilaterally nephrectomized rats treated with deoxycorticosterone and 1% sodium chloride in their drinking water developed severe systemic hypertension with marked cardiac and renal lesions. No pathologic changes could be detected in the retinal vasculature by light microscopy, but electron microscopy revealed inconstant alterations in the pericytes of retinal capillaries: these cells showed hyaloplasmic edema, margination of chromatin, dilatation of rough endoplasmic reticulum, and swelling of mitochondria. Injection of lanthanum into control rats confirmed that this 40-A tracer cannot pass the interendothelial tight junctions. In hypertensive animals, however, it penetrated these junctions and could be visualized in capillary basement membranes and between cells of the retina. The results indicate that an increase in permeability is probably the first pathologic change to occur in the retinal capillaries of hypertensive rats.


Secretory immunoglobulins in colonic neoplasms. Secretory immunoglobulins are found in nongoblet columnar cells of normal intestinal epithelium. These molecules consist of a secretory component portion, which is synthesized in the columnar cells, and an immunoglobulin portion which enters the columnar cells from plasma cells in the adjacent lamina propria. In the present work, the synthesis and transport of these various subunits have been studied by immunofluorescence in benign polyps and cancers of the colon. In both the epithelium and plasma cells of benign and malignant tumors, as well as in normal tissue, IgA is the principal immunoglobulin, followed by IgM. However, when compared to normal tissue, neoplastic epithelium contains less immunoglobulin and also less secretory component; the decrement usually inversely parallels the degree of differentiation. Thus, benign polyps closely resemble normal colonic mucosa in so far as the secretory immunoglobulin system is concerned. In contrast, atypical areas of benign polyps and carcinomas exhibit greatly decreased or absent synthesis and transport of secretory IgA. Plasma cells tend to be markedly decreased in the stroma of carcinomas, suggestive of an alteration in the normal mechanism for attracting the circulating precursors of local IgA plasma cells. Whenever neoplastic epithelium contained IgA, plasma cells with IgA could be observed in the vicinity; this is in keeping with the concept of local synthesis of secretory IgA. In some instances in which local plasma cells were plentiful, neoplastic cells were deficient in secretory component and IgA, which suggested impairment of the mechanisms for transporting IgA across epithelium. The possible role of secretory component in such transport and in attracting lymphoblasts to mucous membranes is dicussed.


Microhemorrhage in the hyperplastic thyroid gland of the rat. A microhemorrhagic process was consistently observed in association with the induction of thyroid hyperplasia by dietary thiouracil in the rat. This process appeared to involve the extravasation of erythrocytes (RBCs) through hyperplastic capillary walls. Those sites of extravasation which were directly visualized involved endothelial openings of less than 1 mu. These openings were surrounded by endothelial cytoplasm containing a dense fibrous material and were associated with RBC constriction during passage. Extravasated RBCs were most often noted singly or in small groups, either in columns between follicular epithelial cells or embedded amongst the basal epithelial infoldings. Occasionally, extravasated RBCs were also observed within follicular lumens. Extravasated RBCs were usually intact ultrastructurally, but occasionally an apparent hemolytic process was observed, both for RBCs embedded amongst epithelial cells and for those within follicular lumens. The nature and etiology of this microhemorrhagic process are considered in relation to the hypervascularity of the gland, the possibility of capillary wall alterations, the presence of endothelial cell mitoses, and the localization of the process.


Microcirculation of the lymph node with metastases. Microangiographic and histologic examination of the popliteal lymph node was performed on 49 rabbits 3 to 55 days after V2 tumor implantation into the hind paw. Control animals received subcutaneous tissue extract from normal rabbit donors. During the first 10 days after the tumor implant from an allogeneic animal donor, the draining lymph node exhibited a hypervascular response which after 2 weeks gradually subsided. Subsequently, during the early stages of lymph node metastasis there was still hypervascularity adjacent to the metastatic deposit. In about 4 weeks the metastases became more established and surrounded by layers of plasma cells. The hypervascular changes of the surrounding lymph node subsided by this time. In lymph node metastases the microvasculature could be an indicator of the immunologic activity of the host.


Mesangial involvement in hemolytic-uremic syndrome. A light and electron microscopic study. Electron microscopic analysis of the mesangial injury in the hemolytic-uremic syndrome was performed in 10 patients. Proteinaceous material similar to that found in the subendothelial region was also seen focally in the mesangium altering the matrix and imparting a reticular appearance. This degenerative process was associated with reparative changes in the glomerular tuft. Many of the mesangial cells were hypertrophied and demonstrated phagocytic activity and peripheral extension of their cytoplasmic processes. Mitotic figures in endothelial as well as mesangial cells were regarded as evidence of a reparative process. Severe mesangial insudation of material containing fibrinogen derivatives resulted in segmental tuft necrosis with almost complete replacement and destruction of the mesangial matrix. On some occasions, a break of the glomerular basement membrane was accompanied by the escape of intraluminal contents into the urinary space, leading to crescentic epithelial cell proliferation.


Experimental induction of erythroblastemia using intravenous carbonyl iron particles. An experimental model is presented whereby erythroblastemia, the appearance of nucleated red cells in circulation, was induced reproducibly in rabbits by intravenous injection of 0.5 to 1 g/kg carbonyl iron particles (CIP). The phenomenon reached a peak in 24 to 48 hours and disappeared after a week. Erythroblastemia was associated with evidence for disseminated intravenous coagulation; both could be aborted by administration of heparin. Repeated injection of CIP was always followed by recurrence of erythroblastemia. For a period as long as 7 months, the animals tolerated repeated injections without evidence of lasting sequelae. Electron microscopic studies of marrow tissue indicated alterations in the red cell nuclei but no alterations in the endothelium of marrow sinuses into which the red cells migrate to reach the circulation. This model provides a means to study the mechanisms involved in nuclear elimination by mammalian red cells.


The renal medulla and mechanisms of hypertension in the spontaneously hypertensive rat. A significant number of offspring from brother-sister matings of NIH-Okamoto-Aoki spontaneously hypertensive rats (SHRs) were found to be normotensive at 20 weeks of age. Over 20% of the animals that were hypertensive at this age had mild-to-moderate unilateral hydronephrosis at the time of sacrifice. In over 90% of the rats that did not develop hypertension spontaneously, ligation of one ureter raised blood pressure above 150 mm Hg within 2 weeks. In those rats made hypertensive by obstructing one ureter and in those that developed hypertension with accompanying naturally occurring hydronephrosis, subcutaneous implants of fragmented renal medulla from unrelated normal rats decreased blood pressure to normotensive levels. In contrast, medullary implants had no significant effect in rats developing hypertension spontaneously without hydronephrosis. Renal inner medullary plasma flow was low in the obstructed kidneys of hydronephrotic hypertensive SHRs but was elevated in the kidneys of nonhydronephrotic hypertensive SHRs. The hypertension in hydronephrotic SHRs appears to be related to an impairment of the antihypertensive function of the renal medulla. Such an impairment of medullary antihypertensive function does not appear to play a significant role in the hypertension in SHRs without hydronephrosis.


Consequences of intramyocardial arterial lesions in aortic valvular stenosis. Proliferative lesions, which included collagen deposition, developed with age in intramyocardial arteries of 27 patients with aortic stenosis and matched controls. Those with the most extensive intramyocardial artery lesions developed massive subendocardial infarcts during surgery. Using histologic quantitation, the percent of intramyocardial arteries with lesions in a patient was correlated with decreases in the amount of muscle in arterioles between the subepicardial and subendocardial zones of the left ventricle. The mean decrease in arteriolar muscle was 43% in patients with aortic stenosis and 19% in controls. Blood pressures correlate with the amount of muscle in arterioles, so subendocardial perfusing pressures were presumably low in those with aortic stenosis. Patients with the greatest decrease in arteriolar muscle across the myocardium had the most impaired left ventricular function, i.e., highest end diastolic pressures, lowest ejection fractions, and lowest mean fiber shortening rates.


Rat platelet aggregation by ATP. Aggregometrical and ultrastructural comparison with aggregations induced by ADP and collagen. This paper describes the aggregation of rat platelets by adenosine triphosphate (ATP). The aggregometry of ATP-induced aggregation and the ultrastructure of ATP-aggregated platelets were compared and contrasted with those of adenosine diphosphate (ADP)-treated and collagen-treated samples. Human platelets were also studied alongside with rat specimens. Several lines of evidence indicate that the ATP-induced aggregation of rat platelet-rich plasma (PRP) is not a result of contaminating ADP in the ATP preparation. ATP did not cause aggregation of human platelets; it inhibited ADP- and collagen-induced human platelet aggregation. ATP pretreated with a creatine phosphate/creatine phosphokinase system caused similar rat platelet aggregation as did ATP not treated with this system. The aggregometry of ATP-induced aggregation of rat PRP was similar to that of collagen-induced aggregation but markedly different from that of ADP-induced aggregation. However, the nature of ATP-induced aggregation was similar to that induced by ADP. Both ATP- and ADP-induced rat platelet aggregations were not affected by adenosine, adenosine monophosphate, or acetylsalicylic acid. The ultrastructure of ATP-aggregated platelets was similar to that of ADP-aggregated ones. It appears that either platelets of rats possess specific ATP receptors or the rat plasma contains a material, lacking or insufficiently present in human plasma, that converts ATP to ADP in a fashion similar to the release of ADP from platelet storage granules.


Acute murine adrenalitis induced by reovirus 3. An ultrastructural study. Reovirus 3 infection of neonatal mice, although characterized primarily by encephalitis, hepatitis, and pancreatitis, also induces an adrenalitis. Histologically, the latter is characterized initially by foci of coagulative necrosis which later enlarge and become surrounded by leukocytic infiltration. Ultrastructurally, the virus was shown to replicate in the paranuclear region of mainly adrenocortical cells but also medullary and endothelial cells. Apoptosis is the most common form of necrosis exhibited and is quickly followed by an infiltration of mononuclear phagocytes which eventually ingest the virus and the cellular debris.


Effects of riboflavin deficiency on the ultrastructure of rat sciatic nerve fibers. Ultrastructural studies indicate that riboflavin deficiency induced by either dietary restrictions alone or with the addition of the antagonist galactoflavin severely affects the structural integrity of myelin lamellae. The degenerative process induced by riboflavin deficiency is time dependent. Nonmyelinated nerve fibers are not affected ultrastructurally by the deficiency. Cellular organelles of both myelinated and nonmyelinated nerve fibers remain intact and presumably functional.


Oxygen toxicity in the newborn. The effect of chronic continuous 100 percent oxygen exposure on the lungs of newborn mice. Continuous exposure of newborn mice of a single, highly inbred strain to 100% oxygen at normal atmospheric pressure for up to 6 weeks resulted in a progressive evolution of pulmonary changes which consisted of dense fibrous tissue deposition, chronic bronchitis and bronchiolitis, and emphysema. Survival of the experimental animals decreased with the duration of exposure, and it was 18% after the sixth week. While the pulmonary changes were evolving, lung growth was markedly inhibited in the experimental animals, whereas lung weight increased significantly. The present study indicates that in contrast to the adult mouse, survival of a substantial percentage of newborn mice for at least 6 weeks is possible, but it is associated with severe changes in pulmonary structure that doubtlessly lead to serious derangement of cardiopulmonary functions.


Eosinophil and neutrophil granulocyte exudation in the Chediak-Higashi (beige) mouse. Humans with Chediak-Higashi syndrome (CHS) and mice carrying the beige mutation have a heritable defect which results in the presence of giant inclusion granules in the cytoplasm in a wide variety of cells and a markedly increased susceptibility to infections. To test whether this increased susceptibility to infection might be a consequence of impaired accumulation of granulocytes at sites of inflammatory-immune stimulation, we quantitated the exudation of granulocytes into the peritoneum in response to secondary tetanus toxoid challenge in normal mice and in two inbred mouse strains with the beige mutation. Neutrophil and eosinophil granulocyte responses in the peritoneal cavity were not diminished in the beige mice as compared to normal mice when previously sensitized animals were challenged intraperitoneally with tetanus toxoid. Since accumulation of cells at the in vivo site of inflammatory immune stimulation did not seem impaired in the mutant beige mice, it would appear that their increased susceptibility to infections is not due to impairment of cellular exudative responses, including the immune components of the eosinophil response.


Occurrence of human pancreatic polypeptide in pancreatic endocrine tumors. Possible implication in the watery diarrhea syndrome. Eighteen endocrine pancreatic tumors were examined for the occurrence of cells producing insulin, glucagon, gastrin, human pancreatic polypeptide (HPP), and vasoactive intestinal polypeptide (VIP) and for A1 cells. More than half of the tumors were mixed, i.e., they contained more than one type of hormone-producing cell. The clinical symptoms were attributable only to one of the hormones produced by the mixed tumors. Three of four tumors causing the watery diarrhea syndrome contained both VIP and HPP cells. In one such tumor there was a strong predominance of HPP cells; the serum HPP levels of this patient were a thousandfold elevated, whereas her VIP levels were within the normal range. Several lines of evidence point to HPP as a possible agent causing the watery diarrhea syndrome. In many of our patients, HPP cells hyperplasia was present in the extratumoral pancreas. Such hyperplasia may give rise to the raised serum HPP levels seen in many patients having endocrine pancreatic tumors.


The children of imprisoned parents: a psychosocial exploration. This study of children's reactions to the imprisonment of a parent identifies temporary behavioral symptoms that commonly follow the incarceration of a parent, as well as antisocial behavior on the part of a few pubertal children. The stigmatizing and traumatizing effects of imprisonment on the spouse and child left behind are discussed, and suggestions for clinical intervention are offered.


Community network therapy: an approach to aiding families with troubled children. This paper outlines a method of working with troubled children that draws upon structural family therapy, school consultation, patient advocacy, and community mental health work. This blending of approaches is presented as the basis for an evolving mode of treatment referred to as community network therapy. Four of its principal dimensions are described, and examples of its clinical application are offered.


Symptom alleviation in the hyperactive child by dietary modification: a report of two cases. Case reports are presented of two hyperactive preschool boys, one with severe cognitive and one with emotional problems, treated as a last resort with the Kaiser-Permanente elimination diet. Outcomes suggest further study of the effectiveness of the diet in alleviating symptoms of hyperactivity, especially in the preschool child who is unresponsive to medication and whose hyperactivity may be compounded by other developmental and emotional problems.


Patients' rights or patients' neglect: the impact of the patients' rights movement on delivery systems. This paper offers a clinician's perspective on the complex and controversial issues related to "patients' rights." It is suggested that such "rights" interpreted and applied literally may contravene the basic right of the individual to receive needed treatment. Related issues are discussed, and a mechanism for exploring resolutions to the conflict between psychiatry and the law is suggested.


Interdisciplinary training and interdisciplinary functioning: a survey of attitudes and practices in community mental health. A survey of staff members and training-program directors suggests that inter-disciplinary functioning is the rule rather than the exception in community mental health centers, although there are significant differences by profession in time spent in interdisciplinary work and in attitudes toward it. Striking parallels are seen within each profession between attitudes of staff and of directors of training programs. Barriers to interdisciplinary functioning and training are identified and discussed.


The informal community caregiver: a link between the health care system and local residents. A group of "informal" caregivers, local people to whom residents turn for information and advice, was identified in the east Harlem community and enlisted in a two-month study. Results suggest that formal human services agencies and their intended clientele would benefit by increased efforts on the part of these institutions to locate and work with community caregivers.


Sexual attitudes and behavior patterns in a middle-class adolescent population. Sexual activities and attitudes of a group of adolescents, who have been followed from early infancy as a part of the New York Longitudinal Study, are reported. Adolescents in the study evince a more matter-of-fact, less fearful attitude than that of previous generations, but do not seem more prone to casual sexual encounters. Sexual conflicts are seen to occur only in relation to overall psychological conflict.


A comparison of racial/ethnic preferences among Anglo, black and Latino children. This study uses a photo-choice method to compare racial/ethnic group preferences of black, Anglo, and Latino children, with a focus on the latter--relatively little-studied--group. While both black and Anglo children choose ingroup photos, Latinos preferred pictures of Anglo children. Explanations of this outcome are explored, and a comparison between the situation of today's Latino child and the black child of ten years ago is suggested.


EMG patterns and forces developed during step-down. These experiments describe electromyographic activity and forces developed during step-down from several heights. The external environment of the experimental subjects was varied by blindfold or Achilles' tendon vibration during descent. EMG activity of the step-down limb, vertical force of impact and knee angle were measured. The results show that the triceps surae muscle contracts prior to the time of impact of the foot with the substrate if information about the step height is supplied to the subject and if the sensory system is not disturbed by vibration. In the presence of vibration or if the step height is unknown, the triceps surae does not contract prior to foot contact. This produces a large force transient which must be absorbed by the skeletal structure, rather than being damped by a lengthening contraction of the triceps surae. The data suggest that the forces developed during ordinary step-down may be the cause of bone and injury in people with impaired vision or in patients with damaged nervous systems who exhibit large responses to vibration.


Passive mechanical factors governing head and neck movements at the onset of sudden falls in the cat. The head and neck movements of 16 cats undergoing sudden, unexpected falls have been assessed as a study preliminary to the investigation of reflex responses to the same stimulus. Six of the cats were studied while normal, and similarly tested at a later date to examine for any changes induced by making these animals pitch and roll insensitive, or by labyrinthectomy. The head and neck always described a sterotyped pattern of movement, consisting of progressive dorsiflexion of the neck without rotation of the head in space. This was unaltered by partial or complete loss of eighth nerve function. These findings are consistent with the head and neck movements of a falling cat being predominantly passive in origin, at least for the first 200 msec or so of an unexpected fall.


Physical anthropology and the dental and medical specialties. The rise of two sub-specialties in Physical Antrhopology traces back to the Anatomy Departments of Schools of Medicine in Germany and France during the nineteenth century. The study of human diversity in bones and bodies was largely by medically-trained anatomists. There developed Medical Antropology and Dental Anthropology, employing osteometry and craniometry on the skeleton, somatometry and cephalometry on the living body. As a result cross-sectional studies gave way to longitudinal studies and X-ray techniques were added to purely mensurational procedures. In Medical Anthropology the specialties most directly concerned are pediatrics, plastic surgery, endocrinology, and orthopaedics. In Dental Anthropology the specialties most directly concerned are pedodontics, orthodontics, oral surgery, and prosthodontics. The contributions of Physical Anthropology to each is discussed.


Similarities between parents and their adopted children. As show in 7,230 parent-child pairs (6,726 biological and 504 adoptive), adoptive parents and their adopted children tend to resemble each other in height, weight and fatfolds to an extent paralleling height, weight and fatfold resemblances of natural (biological) parents and their children. Accordingly, the magnitudes of parent-child resemblances commonly given may not be indicative of the extent of heritability of stature, weight and subcutaneous fat.


Studies of the basicranial axis: a brief review. Growth and development of the cranial base have interested students of anatomical disciplines for more than a century. Flexure of the basal region has been of particular interest and is among the most assiduously studied characteristics of the skull. Reports may be found in journals serving such a diversity of professional interests that a summary of facts and the more interesting speculations on unsettled aspects of this subject should be of value. This paper is a review of the literature from Virschow's and Schaeffer's writings in the latter half of the last century to those of the most recent investigators. It includes the works of anatomists, anthropologists, embryologists and orthodontists, among others.


Long bone growth in Western Eskimo and Aleut skeletons. The pattern of long bone growth in Eskimo and Aleut juvenile skeletons reflects that in living Eskimos and Aleuts. There is a pre-adolescent growth spurt which is particularly intense in females. After age 14 male long bones supercede those of females in length. The characteristic Eskimo and Aleut adult body proportion is established early in childhood. Eskimos and Aleuts have shorter bones than whites at all ages. The difference in length of the forearm and lower leg in comparison with whites appears to increase especially at adolescence.


Some aspects of aging in the lumbar spine. I measured the bodies of vertebrae L3 and L4 of 338 skeletons from the Terry collection in the Smithsonian Institution, including Blacks and Whites, males and females, aged from 20 to 90 years. Transverse breadths of the upper and lower endplates (excluding osteophytes) and minimum transverse breadths all increase with age. In general, the greater broadening occurs in the endplates, but the middle of the body also broadens to such a degree that there is no demonstrable increase in vertebral "flaring" with age. In males, posterior body height decreases relative to anterior height, so that the lumbar bodies become more wedge-shaped with age but females show essentially no change. Anterior height decreases in proportion to minimum breadth, so that the lumbar bodies become relatively lower and broader, and this change is significantly correlated with age in all groups. Midbody height decreases relative to anterior height, so that Nordin's biconcavity index is reduced with age. The increase in biconcavity remains evident even when average anterior-posterior height is used to calculate the index. At all age levels a high percentage of individuals have biconcavity indices of 80% or less, indicating that Nordin's standard of normality for this index, established from measurement on radiographs of the living, should be revised downward for use in evaluating osteoporosis in skeletal populations.


The estimation of sex on the basis of the talus and calcaneus. The present report records and describes sexual dimorphism of the talus and calcaneus in American Blacks and Whites from the Terry Collection housed in the Smithsonian Institution, Washington, D.C. The greater amount of sexual dimorphism was observed in the talus, where 81 percent of the study sample could be accurately sexed. Four discriminant functions based on measurements from the talus and/or the calcaneus allowed sexing 79 to 89% of the study sample accurately. The techniques developed were then applied to two North American Indian samples, and sex of the individuals in these samples was assessed with the same degree of accuracy.


The structure of the human symphysis pubis with special consideration of parturition and its sequelae. Review of the structure of the symphysis pubis, based on my extensive study of the pelvic joints ('31) shows changes from age, function, pregnancy hormones and stress of parturition. Primary physiologic shearing clefts and secondary traumatic clefts in cartilage are more frequent in females. Interdigitations in the young osteocartilaginous border secure the vulnerable growth cartilage against increasing shearing forces. The retropubic eminence, ligamentous or cartilaginous, forms earlier in females, later, due to bony lipping in males, secondary to extrusion of disc cartilage. Ovarian and placental hormones in pregnancy cause remodeling and resorption of the posterior margin of the pubic facette and adjacent cortex, making a (variably) deep bony groove for greatly hypertrophied transverse ligaments. Delivery of a mature infant produces traumatic changes leading to extrusion of torn fibrocartilage in any direction, progressively loosening the symphysis, producing cartilage nodules, cysts and reactive bone formation. Older age degenerative arthritis is more frequent in parous females.


Anterior femoral curvature: its progably basis and utility as a criterion of racial assessment. Stewart ('62) and Walensky ('65) indicated that while the metrical expression of anterior femoral curvature alone will not always differentiate between Whites, American Negroes, and North American Indians, it was very useful as a racial criterion in combination with observed traits such as torsion, pilastry, and cross-sectional shape. Seven additional North American Indian groups reported here, representing both pre-Columbian and post-contact times, upheld the observation that anterior femoral curvature is a useful feature of racial assessment for Negroes, Whites and North American Indians. However, two South American groups studied (Ecuador and Peru) were only slightly more curved than American Negroes, and were less curved than Whites and North American Indians. The metrical expression of anterior femoral curvature therefore is not a useful feature of racial assessment for separating these two South American Indian groups from Whites and American Negroes. Femora of American Negro and White individuals with low ponderal indices were found to be less bowed than the norms for their race; individuals with high ponderal indices were more bowed than the norm for their race. The assumed genetic basis for expression of anterior femoral curvature suggested by Stewart ('62) and Walensky ('65) seems to be a feature of human plastic response to body weight rather than to temporal, clinal, postural or equestrian influences.


Pathology of bedouin skeletal remains from two sites in Israel. Frequency of pathology and of some anomalies in skeletons of Bedouin living about 200 BP, uncovered in the Israeli Negev, is considered in relation to particular bone, sex, age-group, and kinds of defects. The environment of the Bedouin in relation to his "health-status" is noted. Two-thirds of the skeletons had one or more different bones with defects. Incidence of crania with defects was: males, 26%, females, 18%; the highest incidence occurred at age 35-49. Alveolar abscesses occurred in 28% of maxillae, 9% of mandibles. Of the long bones, the tibia was most frequently affected (15%): swelling of the shaft, relatively common, was apparently caused by bejel, a non-venereal form of syphulis, similar to yaws, endemic to the Bedouin. Forty-eight percent had defective vertebrae, usually an arthritic manifestation of one kind or another; half of this group had defects in more than one region of the spine. Defects also occurred relatively frequenly in the innominata, sacrum, scapula, and clavicle, mostly arthritic lesios except in the sacrum in which the percentage with sacral hiatus was high. Average age at death was, males, 43 years, females, 33 years (adults only), and 28 years for all ages.


Physical variation and history in Melanesia and Australia. Local biological variation is marked in Melanesia. Some of it may result from gene flow from Micronesia, but the essential variation appears to result from isolation due to social fragmentation, and to genetic drift in place. In different regions, the variation may correspond well with language relationships, and probably constitutes differentiation which has been preserved over a considerable period, especially since the arrival of horticulture and development of village farming. However, none of this patterning suggests distinct waves of migration into Melanesia. Variation among Australian aboriginal groups is smaller, though far from absent. It may reflect a hunting culture together with social customs allowing more intertribal marriage than is typical of Melanesia. While phenotypically Australians and Melanesias differ, cranially they are closely allied, as against other major human groups. It is suggested that the genetic and phenotypic variety is old, that it existed in the previous home of the Australo-Melanesians (Old Melanesia, comprising present Indonesia and the Phillipines) at least back to 40,000 years ago, and that much of the variation in Melanesia and Australia, including their differences, results from the sampling process involved when different groups out of the original populations made early corssings of the water barriers from Old Melanesia.


Ecology of dental disease.

Ecology of dental disease. Trace elements in the dental enamel of 43 prehistoric Indians from Illinois, Maryland and Virginia show concentration differences by age, sex and geographical locality. Sample areas on an incisor or first molar were blocked off with paraffin, washed twice with distilled water and etched 7 times with 6N HCl. An optical emission spectrophotometer was used to analyze the 9 samples, representing surface contamination and sequential enamel layers. Al, B, Ba, Cu, Fe, K, Mg, Mn, Na, Si, Sr, and Ti were present in most samples in micro or trace quantities; other elements were detected with less regularity. Comparisons of the 2 water washes with the 3 superficial, 4 deep and 7 total acid etches, suggest that during burial the residual inorganic portion of the enamel exchanged little or nothing with the soil. Enamel from archeological teeth may therefore be utilized in host factor studies in dental paleopathology. The Jy 50 Illinois Indians differ from the Potomac Creek, Virginia, Indians both in quantities of elements present and in internal sample variability. In each group, the sexes differ in 4 or more elements, both as to content and variability. Similarly, the older half of each sample differs from the younger. Patterns of sex and age difference are irregular, suggesting cultural differences, rather than physiological, in utilizing the environment during enamel-forming years. Enamel composition, as affected by differential environment utilization, may partially explain sex, age and geographical differences in dental pathology rates.


Within and between race distances in population studies based on discrete traits of the human skull. A battery of 24 discrete cranial traits has been tested for its power to discriminate within- and between-race distances for the two principal North American indigenous populations: Indian (7 samples, N = 366) and Eskimo (7 samples, N = 451). One of the Indian samples, Dakota Sioux, has been split according to tribal subdivisions, the intra-tribal mean distance providing a parameter of very close relationship. In addition, two Negro samples provide a parameter of relationship phylogenetically remote from the Amerinds. Separate male-female analysis of the three largest samples indicates that distances for pooled samples are not seriously affected by the sex component. Within-race distances (C. A. B. Smith's Measure of Divergence, MD), are smaller than between-race at the .00001 level of significance (Mann-Whitney U test) for both Indian-Eskimo and Amerind-Negro comparisons. The features most powerful for Indian-Eskimo and Amerind-Negro comparisons. The features most powerful for Indian-Eskimo discrimination are revealed by their percent contribution to the mean of 49 MD's. The African heritage of American Blacks is reflected in a characteristic Negro pattern of trait frequencies different from the Amerind. This battery of features yields valid taxonomical information useful in conjunction with other physical data to reconstruct affinities of extinct populations.


The skeletal biology of the Virginia Indians. Statistical analysis of one eastern and two western Virginia Indian skeletal samples reveals a general association between geographical and biological distance. However, the data suggest the importance of gene flow as a factor in minimizing local microdifferentiation. Females appear to contribute a disproportionate share to gene flow. This may be attributed to the widespread and apparently frequent practice of acquiring females and children through capture during recurring warfare.


A unique course in anthropology.

A unique course in anthropology. The course in forensic anthropology presented at Florida State University is designed to train criminal investigators in the application of physical anthropological and archaeological techniques to the investigation of buried bodies. Modification of archaeological field techniques by experimentation using artificial graves allows the recovery of fragile and easy to overlook evidence and ensures the recovery of all possible material for analysis by the physical anthropologist. An introduction to physical anthropology enables the criminal investigator to effectively communicate his needs and understand the type of information required for adequate identification of remains by a physical anthropologist.


The Caribou Eskimo: general and specific disease. Reported here are two forms of skeletal pathology identified in an inclusive sample of Caribou Eskimo skeletons. Harris Lines, nonspecific indicators of stress, show marked periodicity in approximately one-half of the observable adults. This pattern is interpreted as the result of a recurrent, annual stress cycle, perhaps attributable to late winter famine. A second form of pathological change comprises resorptive lesions primarily localized in the spinal column and infrequently found on articular surfaces of the appendicular skeleton. Differential diagnosis is developed utilizing attributes of lesion form, lesion distribution, and epidemiology. Emphasis is placed upon deriving objective models which reflect disease in the absence of modern medical intervention. Major forms of pathology known to produce vertebral lesions are included. The model which best fits the Caribou Eskimo data is that of tuberculosis.


Digital dermatoglyphics of three caste groups of Mysore. An analysis of digital pattern types and digital ridge counts was made for samples of three endogamous Mysore castes, viz., Lingayat, Vokkaliga and Adi Karnataka. The pattern types exhibit significant variations between Lingayat and Vokkaliga, and between Adi Karnataka and Vokkaliga, though, in general, distributional trend of the three principal pattern types are of the same order in all the three castes, having high frequency of loops, moderate whorls and low arches. In pattern types, differences between sexes are highly significant. The total ridge count (TRC) in both males and females is lower in the Adi Karnataka than in the Lingayat and Vokkaliga and the same holds good for the counts on each hand. Bimanual differences among the groups are small, and left hand counts in almost all the digits are consistently smaller than those of the right hand in all the castes irrespective of sex. TRC differences between sexes are not significant. It is striking that by contrast with the pattern type frequency data very little difference among the three Mysore castes emerges from the analysis of finger quantitative features, i.e., in total ridge count and pattern intensity index. Overall finger pattern frequencies of the present caste samples fit generally with those observed in other caste groups of Mysore but differ from the frequencies in Madras samples.


Cortical bone loss with age in three native American populations. Age-related thinning of cortical bone was investigated in archaeological populations of Eskimos, Pueblos, and Arikaras. Medial-lateral cortical thickness was measured on radiographs of humerus and femur, and thickness of the anterior femoral cortex was measured directly on samples taken for histologic study. Maximum length of the bones was used to calculate indices of relative cortical thickness, in order to minimize differences due to body size and build. Bone loss in the humerus begins before middle age in all three populations and, except for Eskimo males, the same is true of the anterior femoral cortex. In general, overall female loss of cortical bone amounts to two or three times that of the males, and in the case of the humerus and the anterior cortex of the femur, this difference is evident by middle age. The weight-bearing femoral medial-lateral cortex shows less sexual difference but has the greatest number of statistically significant differences between populations and the greatest contrast between populations in pattern of loss with age. It appears that of the cortical regions studied this is the area upon which environmental factors have the greatest effect, whereas areas more subject to tensile stress, the humerus and anterior femoral cortex, are less affected by these factors.


Temporal variation in prehistoric Nubian crania. Much of the earlier work on the prehistory of Sudanese Nubia has emphasized discontinuity between early Nubian populations. However, recent investigations suggest the converse - that a remarkable degree of cultural and biological continuity exists among indigenous Nubian groups, perhaps as far back as the Paleolithic. Thus, cultural and biological differences between Nubian populations can be most effectively perceived as the result of in situ evolutionary development. The present analysis has two major purposes: (1) to describe the morphological differences in the craniofacial complex between indigenous Nubian populations extending from the A-Group (c. 3,400 B.C.) through the Christian (c. 1,500 A.D.) horizons; and (2) to account for these differences within an evolutionary framework. The multiple discriminant analysis of radiographically derived variables revealed a trend from a substantially lower and more elongated cranial vault to a shorter and taller vault throughout the almost 5,000 year time span. Associated with this pattern was a tendency for the face to become more inferiorly-posteriorly located with respect to the vault in the latter groups. Finally, the masseter and temporalis muscles underwent a reduction and slight relocation through time. We speculate that this trend may be associated with behavioral changes associated with transition from a hunting and gathering to a totally agricultural subsistence pattern.


A note on craniofacial sutural growth.

A note on craniofacial sutural growth. The paper presents and discusses some features of sutural structures. Fibre orientation in sutures seems to be quite variable and associated with minute local growth phenomena. Trabecular patterns in bones, reflecting growth, appear to support the idea of the outside determination of growth. The bevelled and interdigitated structures seen in many sutures may be interpreted as an expedient solution to the problem of fast growth.


Inner medullary plasma flow in the kidney with ureteral obstruction. To test the thesis that ureteral obstruction causes medullary ischemia, we determined inner medullary plasma flow (IMPF) in rats with bilateral or unilateral ureteral obstruction, and after relief of obstruction, by the intravenous 125I-albumin infusion technique. A progressive decline in IMPF was observed during obstruction of 18 h duration, greater in bilateral obstruction (7% of normal at 5h) than in unilateral obstruction (28% of normal at 5 h). The elevation in ureteral pressure was greater and more sustained in bilateral obstruction. After relief of obstruction, IMPF rose to 69-78% of normal in both groups within 2 h. Histologic studies showed tubular necrosis in portions of the inner and outer medulla immediately beneath the renal pelvic epithelium after bilateral or unilateral obstruction of 18 h duration, and India ink perfusion studies showed very poor filling of vasa recta in these areas. The concentrating defect in the postobstructive kidney may be related, at least in part, to damage inflicted by medullary ischemia during obstruction.


Hydrolysis of peptides within lumen of small intestine. The quantitative significance of intraluminal peptide hydrolases in the terminal stages of peptide digestion has been investigated, and the precise origins of these enzymes have been determined. Intestinal contents and mucosae were obtained from rats anethetized with ether. Experiments carried out on pancreaticobiliary secretions and germfree rats show that pancreatic and bacterial enzymes do not contribute significantly toward the luminal digestion  of dipeptides. Chemical assay data, thermostability studies, and examination of electrophoretic mobilities of luminal peptide hydrolases indicate that jejunal enzymes originate predominantly from the cytoplasm of intestinal mucosal cells, whereas the brush border of muosal cells is a major source of the enzymes in the ileum. With glycl-L-phenylalanine and L-phenylalanyl-glycine as substrates, jejunal luminal activity was less than 2.6% of mucosal activity. Brush-border peptide hydrolase activity in ileal contents, however, was 11.9% and 40.7% of mucosal brush-border activity for the two substrates. Luminal enzymes thus play an insignifcant role in the terminal digestion of peptides in the jejunum, but have a much more important role in the ileal digestion of peptides.


Penile pressures and muscle activity associated with erection and ejaculation in the dog. A needle-tipped polyvinyl catheter or subminiature pressure transducer was implanted in the corpus cavernosum penis (CCP), corpus spongiosum penis (CSP), or bulbus glandis to determine the pressure during coitus in 42 dogs. Silver ring electrodes were implanted in the ischiocavernosus (IC) and bulbospongiosus (BS) muscles to monitor the electromyographic (EMG) activity of these muscles. The CCP pressure increased from 26 mmHg in the quiescent state to 161 mmHg at mild erection of the penis in the presence of a receptive female. During the intromission phase of coitus, the mean peak CCP pressure was 5,296 mmHg in the dogs with implanted catheters and 7,434 mmHg in the dogs with implanted transducers. The CCP pressure peaks during intromission were more in phase with the contractile activity of the IC muscles than with the BS muscles. Anesthesia of IC muscles with lidocaine significantly reduced the CCP pressures and the dogs with low pressures were unable to copulate because of insufficient erection for intromission, which indicated that the IC muscles were the source of energy for the high CCP pressure. The mean peak CSP and bulbus glandis pressures during the intromission phase of coitus were 579 and 1280 mmHg, respectively. The contractile activity of the BS muscles was in phase with the CSP pressure peaks. Anesthesia of BS muscles with lidocaine reduced the peak CSP and bulbus glandis pressures during attempted coitus. The mean rupture pressure of the CCP was 86,615 mmHg.


Effect of temperature of resistance to stretch of tortoise muscle. The effects of temperature over the range 5-30 degrees on isometric contraction and resistance to mechanical stretches of the ramp and hold type applied to active muscle have been studied in isolated tortoise gastrocnemius muscles. The isometric tension decreases as the temperature is lowered but, when expressed as a proportion of the isometric tension, the change in tension at the end of the ramp phase of the stretch is increased at the lower temperatures. The proportionate tension change at the end of the hold phase of the stretch could not be directly related to the temperature. An attempt is made to interpret the results in terms of current opinions on the mechanism of the generation of muscular tension.


Age-related changes in Na+ excretion in saline-loaded spontaneously hypertensive rats. The ability of 6- to 7-, 12- to 13-, and 16- to 17-wk-old spontaneously hypertensive rats (SHR) to excrete an acutely administered, isotonic saline load (equivalent to 4.5% body wt) was evaluated. Female SHR from two different colonies were studied. Age-matched female Wistar (W) and Wistar-Kyoto (WKY) rats served as controls. At age 6 wk, the fraction of administered Na+ load excreted by either SHR colony after 60 min was significantly lower than in the Wistar rats but not significank, one colony of SHR excreted significantly more sodium after 60 min than the other rats. Glomerular filtration rate during control periods was positively correlated with age in one SHR colony; no age-related changes were observed in glomerular function in the other groups. These data 1) suggest that WKY rats are more appropriate than the Wistar rats as controls for renal function in the SHR, 2) demonstrate that the ability of the SHR to excrete an acutely administered sodium load is equal to or greater than normotensive WKY controls, and 3) demonstrate that with respect to renal function parameters, the SHR is not a homogenous strain.


Effect of fasting on hepatic ligandin, Z protein, and organic anion transfer from plasma in rats. The effect of fasting on the rate of disappearance from plasma of bromsulphthalein (BSP) and dibromsulphthalein (DBSP), the hepatic content of BSP, and the concentration of ligandin and Z protein, two hepatic organic anion-binding proteins, was studied in the rat. Fasting for 48 h decreased the plasma disappearance of BSP and DBSP and the hepatic content of BSP as well as the amount of ligandin and Z protein. Phenobarbital given prior to fasting partially prevented these changes. A method of quantitation of Z by radioimmunoassay is described. Discrepancies in Z quantiation by dye binding and immunological methods in fasted but not control rats suggest the presence of competitors for organic anion binding to Z in fasting as well as after phenobarbital administration. Results of studies of ligandin turnover during fasting suggest decreased synthesis and increased degradation of the protein. Similar events may be of pathogenetic importance in nonhemolytic unconjugated hyperbilirubinemia observed during fasting in man, horses, and other animals.


Plasma glucagon in pups, decreased by fasting, unaffected by somatostatin or hypoglycemia. In pups less than 4 days old, the mean basal plasma immunoreactive glucagon (IRG) level was about 3 times higher than in adult dogs. This high level decreased with age, and in pups older than 12 days the mean plasma IRG level did not differ from that in adults. Insulin-induced hypoglycemia did not raise plasma IRG concentration in young pups. Fasting decreased plasma IRG in young, but not in older pups. This decrease is consistent with the decrease in gluconeogenesis and in contrast to the metabolic adjustments observed in the adult organism. In pups less than 7 days old, both the pancreas and gastric mucosa contained considerably more IRG than the normal value reported for adult dogs. Gastroduodenal IRG was immunologically indistinguishable from pancreatic glucagon. In pups, somatostatin did not decrease the plasma concentration of either IRG or immunoreactive insulin (IRI) and caused no change in plasma glucose or in the rates of glucose production and utilization calculated from experiments with tracers. The experiments indicate that in pups the pancreatic and gastric alpha-cells are unresponsive to stimuli normally effective in grown dogs.


Mechanical properties of rat cardiac muscle during experimental thiamine deficiency. The intrinsic contractile properties of isolated left ventricular trabecular periods of 24, 40, and 53 days were compared with those from 35 weight-matched food-deprived animals and 25 ad libitum fed controls. Contraction mechanics were measured for each muscle when stretched to the peak of its length tension curve at 28 degrees C in oxygenated Krebs-Henseleit solution. Although both thiamine-deficient and food-deprived groups had a marked diminution in body and left ventricular weight in comparison to ad libitum fed controls, no differences in left ventricular weights from thiamine-deficient and food-deprived rats were observed. In comparison to ad libitum fed control animals, food-deprived rats exhibited a prolongation in the duration of muscle contraction and an augmentation of tension development after 40 days. Upon appearance of neurological signs at an average of 53 days of a thiamine-deficient rats exhibited a decrease in performance associated with a decrease in the duration of contraction and rate of tension development.


Regional shortening patterns in canine right ventricle. The right ventricular outflow tract (OT) is a functionally distinct area of the right ventricle. However, there is little information on the contrdingly, inflow tract (IT) and OT chords and right ventricular free wall segmental changes were measured with implanted ultrasound crystals. The timing and extent of shortening of IT and OT chords and free wall segments were determined both at rest and after stellate ganglion stimulation. At rest, IT chord shortening began 51 ms before OT shortening. OT expansion occurred during this period. IT chord shortening began 51 ms before OT shortening. OT expansion occurred during this period. IT chord shortening was 38% while OT shortening was 34%. In contrast, OT segments did not show systolic expansion. IT segment shortening was 13% while OT shortening was 21%. With stellate stimulation, IT-OT gradients of 15-25 mmHg developed. The lag between IT and OT shortening decreased to 30 ms and segmental shortening increased. We conclude that the OT is a physiologically distinct region which contracts later and remains contracted longer than the IT. Both septal and free wall movements contribute to these changes.


Hepatic cell integrity in hypodynamic states. Changes in liver integrity were studied in isolated perfused cat livers during simulated shock conditions (i.e., combined hypoxia, acidosis, and ischemia) or under the influence of each hypodynamic state separately. The combined hypodynamic stimuli depressed carbon clearance 51% and significantly elevated lactic acid dehydrogenase (LDH) and cathepsin D activities in the perfusate. The perfused liver was more seriously affected by hypoxia than by acidosis or ischemia alone. Reticuloendothelial clearance was depressed 20% and 25% in acidosis and hypoxia, respectively. Hypoxia also induced a 3-fold increase in cathepsin D and a 13-fold increase in LDH activities in the perfusate. After 150 min of hypoxia or ischemia, free cathepsin D in liver tissue increased significantly. The impairment of liver cell integrity (i.e., of Kupffer and parenchymal cells) occurred between 60 and 90 min during simulated shock conditions, indicating that the liver is stable for 60 min when it is exposed to hypoperfusion. The perfused liver is sensitive to local stimuli that predominate in circulatory shock, particularly hypoxia. These stimuli promote the release of lysosomal and cytoplasmic enzymes as well as depress phagocytosis by the reticuloendothelial system, phenomena that exacerbate the shock state.


Inhibitory effects of catecholamines in canine cardiac Purkinje fibers. The effect of catecholamines over a wide range of concentrations was studied on 42K uptake and efflux, as well as on spontaneous rate in canine cardiac Purkinje fibers. Low levels of catecholamines (less than 10(-10) M epinephrine; less than 10(-9) M norepinephrine) decreased automaticity. This negative chronotropic effect was blocked by phentolamine and mimicked by phenylephrine. These low levels of epinephrine and norepinephrine also inhibited 42K uptake by Purkinje fibers but had no effect on 42K efflux. The inhibition of 42K uptake was blocked by phentolamine and verapamil and mimicked by phenylephrine. The data indicate an alpha-receptor-mediated negative response of rate and 42K uptake to low levels of catecholamine. The end result is discussed in terms of a competitive increase in the influx of Ca2+ rather than Na+ and an indirect inhibition of the Na+-K+ pump.


Effect of adrenal enucleation on sodium excretion in the rat. After the adrenal glands are removed without their capsules, so-called adrenal enucleation, rats initially retain sodium, and, after adrenal regeneration, escape from salt retention. To define the renal mechanisms involved in this alteration in salt handling, we have utilized clearance and micropuncture techniques in three groups of saline-expanded rats that were sham-operated (S), enucleated (AE), or escaped after adrenal regeneration (E.) Sodium excretion was clearly blunted after AE, 5.5 mueq/min vs. 20.5 for S and 18.7 for E. Although glomerular filtration rate (GFR) and filtered load of sodium were lower in AE rats, the delivered load of sodium beyond the late distal tubule was not different among the groups: 0.30 neq/min for AE, 0.42 for S, and 0.40 for E. This was a consequence of strikingly greater sodium reabsorption in the loop of Henle and distal tubule in both the S and E rats. In the collecting duct over 50% of the delivered sodium was reabsorbed by the AE rats while over 30% of the excreted sodium was added in this tubular segment in the other groups. These data demonstrate that the impaired natriuresis after adrenal enucleation appears to be due to striking differences in collecting duct function. Since adrenal regeneration in the escape animals reverses this sodium retention, the effect is probably related to some alteration in adrenal hormone production. Sodium excretion in markedly expanded normal rats also appears to be determined by the net addition of sodium in the collecting duct.


Prostaglandin E release in the dog: effect of sodium. Renal arterial injections (20 ml) of 4 M NaCl in 8 dogs and of 0.5 M NaCl in two dogs were followed by significant but delayed increases over 60 min in renal venous prostaglandin E (PGE) concentrations as measured by radioimmunoassay. Perfusion pressure increased significantly only at 5 min but plasma sodium concentration remained above base line for 60 min. In two dogs in which renal artery blood flow was maintained at a constant rate, comparable increases in PGE concentrations were observed. Injections of 1 M mannitol in three dogs and 5% dextrose in water in two dogs did not result in significant changes in PGE concentrations. In four dogs, administration of 50 mg indomethacin 15 min prior to injection of 20 ml of 4 M NaCl abolished the changes of PGE concentration. Sodium appears to have an effect on stimulation of PGE release by the canine kidney. This phenomenon may be of physiologic significance.


Inhibition of ion transport by bile salts in canine gastric mucosa. Studies were conducted with in vivo and in vitro canine stomach preparations. Instillation of 5, 10, and 20 mM bile salts in TES bufer (pH 7.4) into the nonsecreting stomach in vivo caused a progressive decrease in electrical potential difference (PD) and an increase in electrical resitance (R). The rate of acid secretion, determined by the pH-stat method in the histamine-stimulated stomach, decreased with 5 and 20 mM bile salts. Mucosal adenosine triphosphate (ATP) content of the nonsecreting or secreting stomach was reduced by bile salts. In vitro flux studies demonstrated that within the first hour after 1 mM bile salts were added to the mucosal side of the chamber, PD decreased, R increased, and net sodium transport decreased. In the second hour, unidirectional fluxes of sodium increased, indicating an increase in permeability of the gastric mucosa to sodium. These results demonstrate that the initial action of bile salts is inhibition of ion transport, which is followed by an increase in permeability.


Effects of hypoxia on cardiac growth in neonatal rat. To determine whether low oxygen environments enhance cardiac cell division in the neonatal period, newborn rat pups were reared for 21 days in 12-15% oxygen. Left ventricle and right ventricle weights were 30 and 180% greater than controls matched for body weight (P less than 0.001) as were left ventricle/body weight ratios (3.68+/-0.26 vs. 2.99+/-0.05 mg LV/g body wt,P less than 0.001). Left ventricular total DNA and DNA concentration was 95 and 48% greater than controls (P less than 0.001). Autoradiography confirmed that this increase in ventricular DNA resulted from an increased rate of division of cardiac muscle cells, fibroblast, and vascular endothelial cells. When [3H]thymidine was injected on day ), autoradiographs prepared on day 21 reflected an increased dilution of label in hypoxic rats consistent with enhanced proliferation. The labeling index and grains per nucleus of ventricular muscle cells was 25% (P less than 0.01) and 20% (P less than 0.02) less than controls, Thus, hypoxic stress applied early in the neonatal period augments the rate of division and ultimate number of cardiac muscle cells. Whether this enhancement results from a primary effect of oxygen or from secondary hemodynamic factors remains unknown.


Acute isovolemic anemia in anesthetized chickens. Acute isovolemic anemia was produced in anesthetized chickens by serial exchanges of 6% dextran 70 equal to 1% of body weight to quantitate cardiovascular and metabolic parameters. When hematocrit (Hct) and hemoglobin (Hb) levels were reduced by 50% (from 33.3 to 16.3 vol %, and from 10.3 to 5.4 g/100 g, respectively, P less than 0.001), tissue oxygen delivery was maintained by increases in cardiac output (CO), stroke volume (SV), oxygen extraction, and reduced total peripheral resistance (TPR). Heart rate, right atrial pressure, and oxygen consumption (Vo2) were unchanged. Further reductions in Hct and Hb (to 10.8 vol % and 3.7 g/100 g, respectively), were accompanied by cardiovascular failure, as evidenced by falling CO, SV, tissue oxygen delivery, and Vo2. Relative apparent viscosity determinations on the exchanged blood-dextran mixtures indicated that large viscosity changes occurred with the first exchange whereas subsequent exchanges had small incremental viscosity changes. These data indicate that in acutely anemic chickens, oxygen transport capacity was maintained by increased cardiac output and decreased peripheral resistance, unless the severity of the anemia resulted in cardiovascular failure.


Protein composition of lung fluids in anesthetized dogs with acute cardiogenic edema. We measured the protein composition of plasma and lung fluids from nine dogs with cardiogenic edema. To produce the edema, we increased left atrial pressure an average of 36 cmH2O by inflating a balloon catheter in the left atrium, infusing norepinephrine, and infusing large volumes of saline or saline-diluted blood. Blood samples were collected every 15 min, and airway fluid was collected from five dogs that developed severe edema. Terminally, the chest was opened and the lungs were removed. Samples of alveolar fluid were taken from the excised lung by direct pleural puncture with micropipettes. The lungs were frozen in liquid nitrogen and samples of free interstitial fluid were taken from the perivascular and peribronchial cuffs. Plasma and lung fluids were analyzed for total protein by the Lowry method and for albumin-globulin fractions by cellulose acetate electrophoresis. The average total protein concentrations (g/100 ml) were--plasma, 2.65; free interstitial fluid, 1.05; alveolar fluid, 1.23; and airway fluid, 1.29. The average albumin fraction of plasma was 0.40; of alveolar fluid, 0.43; and of airway fluid, 0.43. The protein concentrations in the three lung fluids were nearly identical to each other, but were less than half that of plasma. We conclude that in high-pressure pulmonary edema with alveolar flooding, the capillary endothelium retains the ability to restrict protein relative to fluid filtration, but the alveolar epithelium becomes freely permeable to protein.


Left ventricular function during acute elevation of aortic blood pressure in dogs. Cardiac responses to mechanical constriction of the aorta proximal and distal to the arch arteries and to intravenous infusion of angiotensin were examined in open-chest atropinized dogs during continuous recording of left ventricular and aortic dimensions by means of ultrasonic elements. Proximal constriction reduced stroke volume by 18% both before and during isoproterenol infusion without changing left ventricular end-diastolic pressure, dimensions, or contractility, (dP/dt)IP; angiotensin induced less pronounced increments in stroke volume and end-diastolic volume. By combining proximal constriction with saline-dextran infusion, stroke volume and end-diastolic volume increased as during distal constriction. These results indicate that differences in preload account for the differences in stroke volume responses to proximal and distal aortic constriction. We propose that increased preload is caused by redistribution of blood from capacitance vessels rather than retention secondary to cardiac decompensation.


Inhibitory effect of ethacrynic acid on chloride permeability. Ethacrynic acid inhibits anion movements in ox red blood cells. The I50 for chloride is 7 X 10(-6) M. The inhibitory effect is instantaneous and completely reversed by washing the cells with a Ringer solution, suggesting that reaction with a membrane SH group is not involved in this process. Direct proof that ethacrynic acid does not act by its reactivity with thiol groups is given by experiments with dihydroethacrynic acid, a derivative that lacks the ability to combine with SH groups: the characteristics of inhibition are strictly identical (instantaneous and reversible; I50 equals 9 X 10(-6) M). All the phenoxyacetic derivatives tested were also more or less inhibitory. The relative activity of all the derivatives was highly correlated with their liposolubility, indicating that hydrophobic interaction is important in determining drug effect and influence of steric factors is minimal. The data suggest that inhibition essentially results from a hydrophobic interaction between ethacrynic acid and apolar regions of the membrane protein allowing chloride transport.


Metabolism of ketone bodies by ovine brain in vivo. Ketosis was produced by intravenous infusion (5 mmol/kg per h) of [3-14C]acetoacetate (sp act 0.5 muCi/mmol) into fed and 7-day-fasted sheep. Changes in arterial and sagittal sinus blood samples. During acetoacetate infusion, there was a significant increase in ketone body uptake (P less than 0.001) and conversion to 14CO2 in both fed and fasted sheep. Changes in arterial concentrations and cerebral removal of various metabolites were investigated by simultaneous collection of arterial and sagittal sinus blood samples. During acetoacetate infusion, there was a significant increase in ketone body uptake (P less than 0.001) and conversion to 14CO2 in both fed and fasted sheep when compared to control periods (saline infusion). The percent conversion of ketone bodies to 14CO2 was slightly higher in fasted sheep (22%) compared to fed sheep (18%). Blood glucose and free fatty acid concentrations were decreased, but there was a significant increase in blood lactic acid and lactic acid production by the brain. The plasma insulin concentration was increased significantly both in fed and fasted animals. These results indicate that ovine brain can utilize ketone bodies irrespective of nutritional state. In addition, ketone bodies stimulated the production of lactate by ovine brain.


Effect of ethyl adenosine on myocardial flow after coronary artery occlusion. The effect of ethyl adenosine-5'-carboxylate hydrochloride (EA) was determined in 17 dogs by the radioactive microsphere technique. In both experimental and control animals, microspheres were injected 5 min before (preocclusion period), 60 min after (occlusion period), and 75 min after (saline or vasodilation period) ligation of the left anterior descending coronary artery (LAD). Ten seconds prior to the third microsphere injection, saline was administered to five control animals, and saline with 0.5 mg/kg of EA was given to 12 experimental animals. There was no significant change in myocardial blood flow after saline injection. After EA, mean arterial pressure fell 10% (P less than .001); myocardial blood flow increased 275% (P less than .001) in the nonischemic left circumflex artery (CIRC) area and increased 82% (P less than .01) in the occluded LAD area. In addition, those animals with extensive collateral development showed a significantly greater increase in collateral blood flow than those with minimal collateral development (P less than .05). Thus, EA may increase flow to ischemic areas of myocardium dependent upon the extent of preexistent collateral supply.


Calcium-dependent resistance to stretch and stress relaxation in resting smooth muscles. Mechanical responses to stretch and length-tension relations were examined in rabbit taenia coli, mesenteric vein, aorta, and myometrium and in guinea pig taenia coli made atonic by incubation in Krebs-bicarbonate solution at 20-22 degrees C. When stretched 10% of the length at which maximum active tension is observed (Lo) in 0.5 s, the muscles showed a transient large force (resistance to stretch) that decayed to a new constant level within minutes (stress relaxation). The resistance to stretch decreased markedly in Ca2+-free [disodium ethylene glycolbis-(beta-aminoethylether)-N,N-tetraacetic acid (EGTA)] Krebs but was restored in normal Krebs solution. Calcium removal did not affect the passive length-tension curve. The absence of Ca2+ did not change the steady-state force maintained by the muscle; thus stretch resistance was not due to tone. Blockade of Ca2+ influx associated with electrical activity with 5-[3,4-dimethoxyphenethyl)methylamino]-2-(3,4,5-trimethoxyphenyl-2-isopropylvaleronitrile (D-600) and of Ca2+ release from intracellular sites with thymol (1 mM) completely blocked contraction but did not alter the responses to stretch, thus dissociating the responses to stretch from these processes and tension development. The Ca2+-dependent stress relaxation showed a dependence on muscle length similar to that for active tension development. Except at long muscle lengths, where connective tissue markedly affects length-tension relations, most of the "viscoelasticity" of these smooth muscles is dependent on calcium and may be largely due to the straining of crossbridges that are attached, but not generating a net force, in the resting state.