Latex agglutination tests for measurement of antiplague antibodies.

A latex agglutination test was evaluated as a method for detection and titration of antiplague antibodies. Slide and microtiter techniques using polystyrene latex particles coated with specific fraction-I-antigen of Yersinia pestis were found to be comparable in specificity and sensitivity to serological tests commonly used in laboratory practice. The latex agglutination titers correlated well with those measured by the World Health Organization standard method of indirect hemagglutination, although there was a tendency for the former to be a little lower than the latter. With further study, the latex agglutination test may have application in the seroinvestigation of plague infection in rodents.


Mouse potency assay for Bordetella bronchiseptica bacterins.

A potency assay for Bordetella bronchiseptica bacterins has been developed using mice. The immunogenicities of three bacterins, B, C, and D, were evaluated for ability to prevent death in mice as compared with a reference standard bacterin (RSB-A). Bacterins RSB-A, B, and C were evaluated for ability to prevent death in mice as compared with a reference standard bacterin (RSB-A). Bacterins RSB-A, B, and C were evaluated in swine for efficacy against nasal turbinate atrophy. Swine immunized with RSB-A demonstrated 25% gross nasal turbinate atrophy (GNTA), whereas nonimmunized swine had 85% GNTA. Swine vaccinated with bacterins B and C demonstrated 0 and 100% GNTA, respectively, whereas the nonimmunized groups had 64 and 75% GNTA, respectively. RSB-A and bacterins B, C, and D provided average mouse survivals of 94, 88, 49, and 32%, respectively when the mice were given 1/10,000 of a recommended swine-immunizing dose, whereas an average of 88% of the unvaccinated mice died.


Comparative evaluation of different types of blood culture media for isolation of aerobes.

The possible advantage of hypertonic sucrose medium over isotonic medium for isolating aerobic organisms from blood was studied. Approximately 50 ml of medium and 5 ml of blood inoculum were present in each culture bottle. In the first phase of the study, supplemented peptone broth (SPB) was compared with brucella broth containing 10% sucrose (BB-10S). There were 194 significant clinical isolates in at least one of the two bottles in each set during a 7-month period; 160 (82%) of the isolates grew in SPB, whereas 191 (98%) grew in BB-10S (P less than 0.01). Of the 158 isolates that grew in both media, 13 (8%) appeared earlier in BB-10S, whereas none did so in SPB. In the second phase of the study, SPB with 10% sucrose (SPB-10S) was compared with BB-10S. There were 187 isolates during a 9-month period; 173 (93%) grew in SPB-10S compared with 179 (96%) for BB-10S. In this comparison there was no apparent difference in the time interval required for recovery of organisms. The two hypertonic sucrose media (SPB-10S and BB-10S) were comparable for isolating organisms under aerobic conditions and superior to the nonhypertonic medium (SPB).


Early detection and preliminary susceptibility testing of positive pediatric blood cultures with the Steers replicator.

Early replicator subculturing of blood specimens after 4 to 16 h of incubation detected 135 of 217 (59%) of all positive cultures, including 56 of 64 (87%) Haemophilus influenzae type b, 7 of 22 (32%) Staphylococcus aureus, 19 of 20 (95%) pathogenic streptococci, and 20 of 24 (83%) Enterobacteriaceae. The mean time to detection of the common pediatric pathogens (36 h) was significantly less than that of contaminants (85 h) (P less than 0.001). Blind subculturing to differential media aided in the rapid identification of isolates and the detection of mixed cultures. In addition, a method of obtaining rapid susceptibilities of blood and body fluid isolates to selected antibiotics by blind subculturing to antibiotic-containing media was evaluated. Immediate susceptibility information was obtained for 214 of the 245 (87.3%) isolate-antibiotic combinations. There was complete correlation with a standard Kirby-Bauer reading for 94.9% of these observations. Replicator blood subculturing before 24 h of incubation results in early detection of the majority of pediatric pathogens. The inoculation of additional differential and antibiotic-containing media with each blind subculture aids in rapid identification of isolates and may give limited, but clinically important, immediate susceptibility information.


Effect of freezing on the viability of Mycobacterium paratuberculosis in bovine feces.

Three bovine fecal specimens were cultured for Mycobacterium paratuberculosis before freezing and after frozen storage at -70 degrees C for 3 and 15 weeks. The losses in viability from 0 to 3 weeks of storage were significant (P = 0.01) for all three samples. The losses in viability between 3 and 15 weeks of storage were not significant (P greater than 0.05) for two specimens in which the M. paratuberculosis occurred naturally, but the loss was significant (P = 0.01) in a simulated specimen (M. paratuberculosis culture added to feces from a healthy cow).


Isolation of bacteriophage from Thermoactinomyces.

Bacteriophages were isolated from strains of Thermoactinomyces vulgaris, T. candidus, and T. sacchari used to produce antigen for hypersensitivity pneumonitis screening at the Marshfield Medical Foundation. Whereas the one phage isolated from T. sacchari and two phages from T. vulgaris were species specific, three other phages isolated from T. vulgaris and the two phages isolated from T. candidus were infectious for both T. vulgaris and T. candidus, thus indicating a close relationship between these two species. A simple reproducible scheme for classification of newly isolated T. vulgaris-T. candidus phages into seven groups on the basis of host range is presented. Examination of plaque morphology of the T. vulgaris-T. candidus phages supported the host range classification scheme. The ease of isolation of phages from cultures of Thermoactinomyces suggests that they are commonly associated with this genus.


Group VE-2 (Chromobacterium typhiflavum) bacteremia.

Group VE-2 (Chromobacterium typhiflavum) bacteremia occurred in a severely traumatized, post-neurosurgical patient. A discussion of the clinical occurrence of the organism, bacteriological characteristics, and antibiotic sensitivities is presented.


The effect of granulomatous pulmonary disease in dogs on the response of the pulmonary circulation to hypoxia.

We studied the effect of diffuse granulomatous pulmonary disease on the reponse of the pulmonary circulation to hypoxia in two series of experiments in intact dogs. First, in animals with unilateral disease, vasoconstriction in the diseased lung was compared to that in the contralateral control lung. Second, in animals with bilateral disease, the vasoconstriction of pulmonary shunt pathways was compared to that of the rest of the pulmonary vasculature. We assessed vasoconstriction in each study by measuring the distribution of pulmonary blood flow between the test and control set of vessels during 21 and 12% oxygen breathing. In the first set of experiments, we measured apportionment of the blood flow between the two lungs by bronchospirometry and the krypton bolus method. In normal dogs, hypoxia did not shift blood flow systematically from one lung to the other. In 10 dogs with unilateral disease, general hypoxia increased the proportion of blood flow to the diseased lung. The mean percent of blood flow to the left lung in eight dogs with disease in that lung rose from 29% during air breathing to 32% (P < 0.001). In the second set of experiments, we measured apportionment of the blood flow between shunt pathways and gas-exchanging pathways by a constant infusion of radio-active krypton and the standard shunt formula. In eight dogs with bilateral disease, hypoxia consistently increased the flow through shunt pathways, from a mean value of 10% of pulmonary blood flow to 14% (P < 0.005).Thus, diffuse granulomatous disease causes a decreased vasoconstrictive response to hypoxia both in diseased, gas-exchanging regions and in shunt pathways. In proliferative interstitial pulmonary disease, generalized hypoxia causes shifts in pulmonary blood flow which do not ameliorate but rather worsen the hypoxemia of systemic arterial blood.


Lanthanum probe studies of cellular pathophysiology induced by hypoxia in isolated cardiac muscle.

This study was undertaken to evaluate directly the relationship between evolution of irreversible myocardial injury induced by hypoxia in an isolated papillary muscle preparation and the development of pathophysiological alterations related to severely impaired membrane function. An ionic lanthanum probe technique was employed as a cytochemical marker to monitor the progression of cellular injury, and data from this cytologic technique were correlated with ultrastructure and measurements of contractile parameters in a total of 67 muscles subjected to control conditions or to graded intervals of hypoxia with or without reoxygenation. Marked depression of developed tension and rate of tension development occurred after 30 min of hypoxia. Contractile function showed significant recovery with reoxygenation after 1 h and 15 min of hypoxia but remained depressed when reoxygenation was provided after 2 or 3 h of hypoxia. Examination by transmission and analytical electron microscopy (energy dispersive X-ray microanalysis) revealed lanthanum deposition only in extracellular regions of control muscles and muscles subjected to 30 min of hypoxia. After hypoxic intervals of over 1 h, abnormal intracytoplasmic and intramitochondrial localization of lanthanum were detected. After 1 h and 15 min of hypoxia, abnormal intracellular lanthanum accumulation was associated with only minimal ultrastructural evidence of injury; muscle provided reoxygenation after 1 h and 15 min of hypoxia showed improved ultrastructure and did not exhibit intracellular lanthanum deposits upon exposure to lanthanum during the reoxygenation period. After 2 to 3 h of hypoxia, abnormal intracellular lanthanum accumulation was associated with ultrastructural evidence of severe muscle injury which persisted after reoxygenation. Thus, the data support the conclusion that cellular and membrane alterations responsible for abnormal intracellular lanthanum deposition precede the development of irreversible injury but evolve at a transitional stage in the progression from reversible to irreversible injury induced by hypoxia in isolated feline papillary muscles.


Reversal of advanced digitoxin toxicity and modification of pharmacokinetics by specific antibodies and Fab fragments.

The effects of Fab fragments of high-affinity specific antibodies have been studied in a canine experimental model of lethal digitoxin toxicity. Selected antiserum from sheep immunized and boosted with a digoxin-serum albumin conjugate contained antibodies that cross-reacted with digitoxin with an average intrinsic association constant of 1.4 x 10(10) M(-1) as determined by equilibrium dialysis. Rapid second-order association kinetics (k(f) = 3.7 x 10(6) M(-1) per s) and slow dissociation kinetics (k(r) = 1.9 x 10(-4) per s) were documented for the antibody-digitoxin complex. Eight dogs given 0.5 mg/kg digitoxin intravenously developed ventricular tachycardia after 23+/-4 (SEM) min. Control nonspecific Fab fragments were then given. All animals died an average of 101+/-36 min after digitoxin administration. Another eight dogs given the same digitoxin dose similarly developed ventricular tachycardia after 28+/-3 min. This group then received a molar equivalent dose of specific Fab fragments intravenously over 3 min, followed by a 30-min infusion of one-third of the initial dose. All dogs survived. Conducted sinus beats reappeared 18+/-4 min after initial Fab infusion, and stable normal sinus rhythm was present at 54+/-16 min. Plasma total digitoxin concentrations increased threefold during the hour after initial Fab infusion, while plasma free digitoxin concentration decreased to less than 0.1 ng/ml. Effects on digitoxin pharmacokinetics of these Fab fragments and the antibody population from which they were derived were further investigated in a primate species. Unlike common laboratory animals previously studied, the rhesus monkey was found to have a prolonged elimination half-life, estimated at 135 and 118 h by radioimmunoassay and [(3)H]digitoxin measurements, respectively, similar to man and thus providing a clinically relevant experimental model. Intravenous administration of 2 mol of specific Fab fragments per mole of digitoxin 6 h after 0.2 mg of digitoxin produced a rapid 4.3-fold increase in plasma total digitoxin concentration followed by a rapid fall (t((1/2)) 4 h) accompanied by a 14-fold enhancement of urinary digitoxin excretion over control values during the 6-h period after Fab was given. Analytical studies were consistent with increased excretion of native digitoxin rather than metabolites, and the glycoside was found in equilibrium dialysis studies to be excreted in the urine in Fab-bound form. Administration of 2 mol of specific antibody binding sites per mole of digitoxin as intact IgG caused a greater and more prolonged increase in plasma total digitoxin concentration, peaking 13-fold above control levels. In contrast to the effects of Fab, however, specific IgG reduced the rate of urinary digitoxin excretion substantially below control values. We conclude that Fab fragments of antibodies with high affinity for digitoxin are capable of rapid reversal of advanced, otherwise lethal digitoxin toxicity, and are capable of reducing the plasma half-life and accelerating urinary excretion of digitoxin.


Parathyroidectomy reduces 25-hydroxyvitamin D3-1 alpha-hydroxylase activity in the hypocalcemic vitamin D-deficient chick.

To test the hypothesis that in the vitamin D-deficient state the activity of 25-hydroxyvitamin D3-1 alpha-hydroxylase (25-OHD3-1 alpha-hydroxylase) is modulated by parathyroid hormone and the plasma concentration of phosphate only in the presence of small amounts of 1,25-dihydroxyvitamin D3 (or some other metabolite of vitamin D), we measured the activity of this enzyme 24 h after parathyroidectomy (PTX) in frankly hypocalcemic, vitamin D-deficient chicks that were not supplemented with vitamin D or one of its metabolites. The otherwise predictable complications of PTX in this metabolic setting (hypocalcemia of increasing severity, tetany, moribundity, and death) were prevented by continuous intravenous administration of calcium (as a solution of calcium chloride/calcium gluconate 1:1) through a catheter in the external jugular vein placed at the time of PTX. The findings were as follows: (a) The activity of 25-OHD3-1 alpha-hydroxylase was significantly less in the parathyroidectomized group than in the sham-operated control chicks (P less than 0.001). (b) The reductive effect of PTX on the activity of this enzyme was significantly attenuated when hypophosphatemia was increased in severity by administration of glucose. (c) In the post-PTX state the activity of 25-OHD3-1 alpha-hydroxylase and plasma concentration of phosphate were significantly, inversely related (P less than 0.001). (d) In the sham-operated control group the activity of this enzyme and the plasma concentration of phosphate were not significantly correlated. These findings indicate that in the vitamin D-deficient state, both circulating parathyroid hormone and the plasma concentration of phosphate can significantly modulate the activity of 25-OHD3-1 alpha-hydroxylase in the absence of vitamin D or its metabolites. The findings also suggest that in the vitamin D-deficient state the plasma concentration of phosphate modulates the activity of this enzyme only when the concentration of circulating parathyroid hormone is not increased.


Study of factors causing excess protoporphyrin accumulation in cultured skin fibroblasts from patients with protoporphyria.

The activity of heme synthetase, which catalyzes the chelation of ferrous iron to protoporphyrin to form heme, is deficient in sonicates of skin fibroblasts cultured from patients with protoporphyria. During culture in Eagle's medium supplemented with fetal calf serum, these cells do not accumulate protoporphyrin, however. This may be due to a minimal requirement for heme synthesis, since glycine is incorporated into heme at a low rate which is similar to that in normal fibroblasts. In addition, the activity of delta-aminolevulinic acid (ALA) synthetase, the first and rate-limiting enzyme of heme biosynthesis which catalyzes the formation of ALA from glycine, is normal in lysates of the fibroblasts. Cultured fibroblasts were therefore incubated with ALA in order to bypass the rate-limiting step of heme biosynthesis. In the presence of 25 muM iron, protoporphyrin was detected in protoporphyria cell lines when the concentration of ALA in the medium reached 50 muM, but not in normal lines. As the concentration of ALA was increased above 50 muM, all lines accumulated protoporphyrin. However, the amount was 2-3 times more in cultured fibroblasts from patients with protoporphyria, reflecting their deficiency of heme synthetase activity. When iron was not added to the medium, protoporphyrin accumulated to a similar degree in normal and protoporphyria fibroblasts; this was significantly more than that in the presence of iron. These studies indicate that excessive protoporphyrin accumulation in protoporphyria, which is due principally to deficient heme synthetase activity, may be modified by the rate of ALA formation in heme-producing tissues, and by the availability of iron.


Lead poisoning. Further observations on erythrocyte pyrimidine-nucleotidase deficiency and intracellular accumulation of pyrimidine nucleotides.

Pyrimidine nucleotides, detectable in normal erythrocytes only in trace quantities if at all, were found to comprise 7-80% of the intracellular nucleotide pools in nine subjects with severe lead over-burden. Blood lead concentrations ranged from approximately equal to 200- to 400-microgram/dl packed cells, and the greatest accumulations of pyrimidine-containing nucleotides occurred in the two subjects with the highest blood lead levels. Most of the patients had mild or moderate anemia and moderate basophilic stippling evident in Wright's-stained peripheral smears. Pyrimidine nucleotidase activities were inhibited to 13-28% of the mean activity in normal control erythrocytes and even more so (5-15%) when compared to specimens with increased reticulocytes and young cells. Reticulocytosis was absent in two subjects and modest to moderate in the remainder, but erythrocyte assays revealed the substantial elevations in populations of young mean cell age. Inappropriately low reticulocyttial elevations in glucose-6-phosphate dehydrogenase expected in populations of young mean cell age. Inappropriately low reticulocyte responses may reflect hematopoietic suppressive effects of lead at a variety of metabolic loci.


Immunoheterogeneity of parathyroid hormone in venous effluent serum from hyperfunctioning parathyroid glands.

The immunoreactive parathyroid hormone (iPTH) in the plasma of hyperparathyroid man consists largely of carboxyl (COOH)-terminal fragments of the hormone. Although these fragments have been thought to arise principally or solely from peripheral metabolism of intact human PTH {hPTH(1-84)} secreted from the parathyroid gland, there is disagreement about the source of iPTH fragments in vivo. To reexamine this question, we fractionated peripheral and thyroid or parathyroid venous effluent sera from four patients with primary hyperparathyroidism using a high-resolution gel filtration system (Bio-Gel P-150 columns run by reverse flow). The column effluents were analyzed using two PTH radioimmunoassays, one directed toward the amino(NH(2))-terminal region of the molecule, the other toward the COOH-terminal region. In all four thyroid or parathyroid venous effluent sera studied, iPTH was 9-180 times higher than in peripheral serum from the same patient; after fractionation, hPTH(1-84) accounted for only a portion of the total iPTH (35-55% with the assay directed toward the COOH-terminal region of hPTH, >90% with the NH(2)-terminal directed assay.) The remaining iPTH eluted from Bio-Gel P-150 after hPTH(1-84) as NH(2)-or COOH-terminal hPTH fragments. These results suggest that parathyroid tumors secrete large quantities of hPTH fragments. Based on estimates of their molar concentrations in serum, tumor-secreted COOH-terminal hPTH fragments could account for most of these peptides in peripheral serum if their survival times were, as estimated by several other workers, 5-10 times that of hPTH(1-84). We conclude that, in contrast to published information, secretory products of hyperfunctioning parathyroid tissue are probably a major source of serum PTH immunoheterogeneity.


Association of factor XI and high molecular weight kininogen in human plasma.

Factor XI and high molecular weight kininogen were found associated in normal human plasma at mol wt 380,000 as assessed by gel filtration on Sephadex G-200. The molecular weight of Factor XI in high molecular weight kininogen-deficient plasma was 175,000, the same value obtained for purified Factor XI. When high molecular weight kininogen-deficient plasma was reconstituted with purified high molecular weight kininogen, all of the Factor XI was then found at mol wt 380,000. Complex formation was also demonstrable upon incubation of Factor XI and highly purified high molecular weight kininogen. This complex was distinct from the prekallikrein-high molecular weight kininogen complex; thus high molecular weight kininogen forms bimolecular complexes with either Factor XI or prekallikrein but does not form a trimolecular complex that includes both Factor XI and prekallikrein. Neither Hageman factor nor plasminogen were found associated with high molecular weight kininogen; binding to high molecular weight kininogen appeared to be a specific property of the Hageman factor substrates.


Absorption, plasma transport, and cellular retention of cobalamin analogues in the rabbit. Evidence for the existence of multiple mechanisms that prevent the absorption and tissue dissemination of naturally occurring cobalamin analogues.

Analogues of cobalamin (Cbl; vitamin B(12)) are prevalent in nature as a result of bacterial synthesis, and are of additional interest because of their potential use as antimetabolites and chemotherapeutic agents. We have synthesized 14 Cbl analogues containing (57)Co and have compared their gastrointestinal absorption, plasma transport, and cellular retention to that of [(58)Co]Cbl in rabbits. Many of the Cbl analogues were bound with low affinity by intrinsic factor, and none of these [(57)Co]Cbl analogues were taken up by the ileum or absorbed into the body in amounts comparable to that of [(58)Co]Cbl. The Cbl analogues that were bound by intrinsic factor with high affinity were taken up by the ileum but, in many cases, they were retained there in significant amounts. Most of the Cbl analogues were bound by plasma transcobalamin II with high affinity and all of these transcobalamin II-[(57)Co]Cbl analogue complexes were taken up by a variety of tissues in a manner that was indistinguishable from that of transcobalamin II-[(58)Co]Cbl. The few analogues that were bound by transcobalamin II with low affinity were taken up by tissues in lesser amounts, and 20-70% of these analogues was rapidly excreted in the urine as occurs with native Cbl when it is present in plasma in unbound form. All of the Cbl analogues were bound by the granulocyte R-type Cbl-binding protein with high affinity and all of the R-type protein-[(57)Co]Cbl analogue complexes were cleared rapidly from plasma exclusively by hepatocytes as occurs with R-type protein-[(58)Co]Cbl. Some Cbl analogues were released back into the plasma and were disseminated among a variety of tissues via transcobalamin II as occurs with native Cbl. Other Cbl analogues were retained in the liver and eventually excreted in the feces and urine without accumulating in other tissues. These studies indicate that intrinsic factor and the ileum prevent certain Cbl analogues from entering the body and that the granulocyte R-type protein and hepatocytes prevent the dissemination of certain Cbl analogues that may gain entry such as during infections with Cbl analogue-producing bacteria. The fact that transcobalamin II binds and transports a large number of Cbl analogues indicates that these protective mechanisms can be circumvented and supports the feasibility of using Cbl analogues as antimetabolites in vivo.


Effect of 1,25-dihydroxyvitamin D3 on the renal handling of Pi in thyroparathyroidectomized rats.

The kidney adapts its tubular capacity to transport inorganic phosphate (P(i)) according to the dietary supply of P(i) in both intact and thyropara-thyroidectomized (TPTX) rats. However, in TPTX rats the capability of the renal tubule to adapt to a high P(i) diet is diminished. In TPTX rats the production of the active vitamin D(3) metabolite, 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], is also reduced. 1,25-(OH)(2)D(3) has been shown to have a marked effect on P(i) metabolism. Therefore the question arises whether the deficient production of 1,25-(OH)(2)D(3) contributes to the alteration of the tubular transport of P(i) observed in chronically TPTX rats. In the present investigation, vitamin D-replete rats were sham operated (SHAM) or thyroparathyroidectomized and then pair fed diets containing either 0.2 or 1.2 g/100 g P for 7 days. During this period, groups of SHAM and TPTX rats received i.p. 2 x 13 pmol/day of 1,25-(OH)(2)D(3), a dose which was shown to just normalize the decreased intestinal absorption of Ca and P(i) in TPTX rats. The capacity of tubular P(i) transport was then assessed by measuring the fractional excretion of P(i) (FEP(i)) at increasing plasma P(i) concentration ([P(i)](Pl)) obtained by acute infusion of P(i). The results show that in SHAM rats fed either P diet, 1,25-(OH)(2)D(3) has no effect on the renal handling of P(i). In TPTX rats fed 1.2 g/100 g P diet, 1,25-(OH)(2)D(3) increases FEP(i) over a wide range of [P(i)](Pl.) In TPTX rats fed a 0.2 g/100 g P diet, 1,25-(OH)(2)D(3) does not alter FEP(i) up to a [P(i)](Pl) of 3.0-3.5 mM, but does increase it at higher [P(i)](Pl.) In fact, on both diets TPTX rats supplemented with 1,25-(OH)(2)D(3) appear to have the same renal handling of P(i) as SHAM counterparts. The effect of 1,25-(OH)(2)D(3) was not associated with a change in urine pH or in urinary excretion of cyclic AMP and was maintained under marked extracellular volume expansion. It was associated with a rise in plasma calcium in the TPTX rats fed the high, but not the low, P diet. In TPTX rats fed 1.2 g/100 g P diet, 25-hydroxyvitamin D(3) in doses of 2 x 130 or 2 x 1,300 pmol/day i.p. did not increase FEP(i.)In conclusion, 1,25-(OH)(2)D(3) administered in physiological amounts to TPTX rats restores to normal the capability of the renal tubule to excrete P(i) and to adapt to large variation in dietary P(i). The results suggest that 1,25-(OH)(2)D(3) plays an important role in the regulation of the renal handling of P(i) and that the chronic change in the tubular capacity to transport P(i) after TPTX may be due to the decreased formation of 1,25-(OH)(2)D(3).


The interaction of dietary fibers and cholesterol upon the plasma lipids and lipoproteins, sterol balance, and bowel function in human subjects.

To identify any metabolic effects of dietary fiber upon cholesterol metabolism in man, six adult volunteer subjects were fed eucaloric cholesterol-free formula diets, with and without added dietary fiber for two 4-wk periods. A large quantity of dietary fiber was fed, some 60 g of plant cell wall material (or 16 g of crude fiber) derived from corn, beans, bran, pectin, and purified cellulose. This provided about five times the fiber intake of the typical American diet. The addition of fiber to the cholesterol-free diet did not change either the plasma cholesterol level (171+/-21 mg/dl, SEM, to 167+/-18) or the triglyceride (103+/-39 to 93+/-27 mg/dl). The excretion of both endogenous neutral steroids and bile acids were unchanged with fiber (505+/-41 to 636+/-75 mg/day and 194+/-23 to 266+/-47 mg/day, respectively.) However, total fecal steroid excretion was increased 699+/-29 to 902+/-64 mg/day, P < 0.025). With fiber, intestinal transit time was decreased (59+/-9 to 35+/-8 h, P < 0.005), and both the wet and dry stool weights were greatly increased.A second group of six subjects was fed similar diets containing 1,000 mg cholesterol derived from egg yolk. The addition of fiber to the 1,000-mg cholesterol diet did not alter either plasma cholesterol level (233+/-26 to 223+/-36 mg/dl) or triglyceride (102+/-19 to 83+/-11 mg/dl). The excretion of endogenous neutral steroids (618+/-84 to 571+/-59 mg/day), of bile acids (423+/-122 to 401+/-89 mg/day), and of total fecal steroids (1,041+/-175 to 972+/-111 mg/day) were unchanged by fiber. The absorption of dietary cholesterol was not altered when fiber was added to the 1,000-mg cholesterol diet (44.0+/-3.3 to 42.9+/-2.5%). A two-way analysis of variance utilizing both groups of subjects indicated a significant (P < 0.001) effect of dietary cholesterol upon the plasma cholesterol concentration. We concluded that a large quantity of dietary fiber from diverse sources had little or no effect upon the plasma lipids and sterol balance in man in spite of the fact that intestinal transit time and stool bulk changed greatly.


The interrelationship between the release of renin and vasopressin as defined by orthostasis and propranolol.

The concentration of both plasma renin and plasma arginine vasopressin rose in normal subjects after an 85 degrees head-up tilt. Plasma renin activity, which increased 70-80% above the supine value, was maximal at 15 or 30 min, whereas the six- to seven-fold increase of plasma arginine vasopressin concentration was observed between 30 and 45 min. Intravenous propranolol administered just before tilt was used to investigate the possibility that the delayed rise of arginine vasopressin was stimulated by renin. Although the response of plasma renin was completely abolished by propranolol, the response of vasopressin was unaffected. These findings suggest that the release of vasopressin that follows isosmolar hypovolemia achieved by orthostasis may occur independently of changes in the renin-angiotensin system in the presence of propranolol.


HBsAg, chronic lymphoproliferative disorders, and cirrhosis of liver.

This study reports the incidence of HBsAg in a series of chronic lymphoproliferative disorders in which a high incidence of cirrhoses had been previously observed. Twenty-three cases were collected from the necropsy records. The type of lymphoma was reviewed in the light of the new functional classifications of non-Hodgkin malignant lymphomas introduced by Lennert and Lukes. The presence of HBsAg in the liver was investigated by the indirect immunofluorescence technique. Eleven cases showed plasmocytoid features and were considered as immunocytomas. Seven cases showed cirrhosis of the liver; six of them belonged to the immunocytoma group. Four cases were positive for HBsAg. Three of them were found among the group combining cirrhosis and immunocytoma. They presented the abundant nodular distribution of HBsAg typical of inactive cirrhosis.A parallel is drawn between the often reported association of Waldenström's syndrome and cirrhosis and the association of immunocytoma and cirrhosis observed in this study. The analogy is all the more justified since most of the lymphomas associated with Waldenström's syndrome happen to be immunocytomas. Therefore the association between HB virus infection and cirrhosis on the one hand and chronic lymphoproliferative disorders on the other may not be purely coincidental. A chronic antigenic stimulus such as persisting HBsAg could trigger the proliferation of a malignant lymphoid clone.


Lymphocyte tubular structures in rheumatoid arthritis.

Two types of lymphocyte tubular structures were studied by electron microscopy in 80 patients with classic or definite rheumatoid arthritis (RA). Fifteen patients with unequivocal systemic lupus erythematosus (SLE) and 10 healthy persons were studied as controls. Lymphocyte tubulo-reticular structures were found in 13 of the 80 patients with RA and in 10 of the 15 patients with SLE. No tubuloreticular structures were found in any of the healthy subjects. In the RA patients antinuclear antibodies, LE cell phenomenon, and chlorambucil treatment were associated significantly with these inclusions but disease activity was not related to their presence. In cases in which tubuloreticular structures were present the number of cells containing inclusions was on average much lower in patients with RA than in those with SLE. Lymphocyte tubular parallel arrays were found in all the patients with RA and SLE and in all the healthy persons. In all three groups the average number of cells containing parallel tubular arrays was similar.


Subacute bacterial endocarditis due to Actinobacillus actinomycetemcomitans. Report of a case with a review of the literature.

A case of subacute bacterial endocarditis due to Actinobacillus actinomycetemcomitans is reported. The patient was successfully treated first by a combination of gentamicin and ampicillin and then, because of severe allergic reactions, ampicillin was replaced by co-trimoxazole; symptoms did not recur and blood cultures remained sterile. A synoptic table is presented of 19 reported cases of infection caused by A. actinomycetemcomitans not connected with actinomycosis, with particular regard to their clinical features, treatment, and outcome.


Two cases of monoclonal immunoglobulins with antistreptolysin activity: clinical and laboratory study.

In two patients with a persisting, high antistreptolysin titre the antistreptolysin activity in both cases resided exclusively in a monoclonal IgG component in the serum. This component had all the characteristics of a true antibody. A history in both patients of arthritis with or without angina suggested that the monoclonal antibodies were reactive in origin, although definite proof was lacking. In one case there was a suggestion of incipient myeloma. Whenever an extremely high antistreptolysin titre persists after antibiotic treatment the possibility of paraproteinaemia should be considered.


Abnormal lipoproteins in multiple myelomatosis.

In a study of the lipoprotein pattern in multiple myelomatosis electrophoresis on agarose gel showed abnormal lipoproteins, named paralipoproteins (p-Lp), in 24 out of 30 normolipidaemic patients. These paralipoproteins were grouped according to their mobility into one or another of the following types: (1) p-Lp1 with a mobility identical with that of gamma-globulin, (2) p-Lp2 with a mobility between that of beta- and gamma-globulin, (3) p-Lp3 with a mobility identical with that of beta-globulin. On ultracentrifugation the abnormal lipoproteins were found to have a density above 1-063 g/ml.


IgG myeloma presenting as ulcerative colitis.

Two patients who presented with ulcerative colitis are described. Both were found to have evidence of IgG monoclonal gammopathy and Bence-Jones proteinuria. This association has been reported previously only in the presence of myelomatous infiltration of the gastrointestinal tract or in amyloidosis, and hence the cases reported appear to be unique.


Acquired cystic disease of the kidneys: a hazard of long-term intermittent maintenance haemodialysis.

In the period 1968-76, necropsies were carried out on 30 patients who had been treated by long-term intermittent maintenance haemodialysis. Fourteen of these patients developed bilateral cystic disease of the kidney. Clinical, pathological, and radiological investigation of these patients when they first presented did not reveal any evidence of renal cystic change. The main complications of this condition are haemorrhage and tumour formation. Six patients developed renal tumours, and in five cases these were multiple. The histological appearance of these neoplasms gave no indication as to whether they would behave in an aggressive manner. One patient died of metastatic carcinomatosis from a renal primary. The condition of acquired cystic disease of the kidney should be suspected if patients on maintenance haemodialysis suffer from recurrent haematuria or are found to have enlarging kidneys.


Carcinoembryonic antigen in thyroid disease.

Plasma carcinoembryonic antigen (CEA) levels were measured by the Z-Gel technique in 138 patients with benign thyroidopathies, 25 patients with thyroid cancer, and 141 normal persons. Levels were raised (above 5 ng/ml) in 2% of the normal subjects, in none of the patients with benign thyroidopathies, and in 20% of the patients with thyroid cancer. They were considerably raised in all cases of medullary carcinoma of the thyroid but they were also high in other histological types of thyroid cancer. Measurement of plasma CEA may be of value in the preoperative diagnosis and follow-up of patients with thyroid cancer.


Standardisation of a simple method for the determination of antithrombin activity.

A procedure is described for performing a functional assay of serum antithrombin activity. The method consists of adding serum to a thrombin solution and measuring, after a fixed incubation time, the residual thrombin activity on a substrate plasma. The mean serum antithrombin activity found in 96 healthy blood donors using this procedure was 109.5% (range 82%-160%). The method was linear over an activity range between 30.5% and 176%, was significantly correlated with antithrombin-III protein concentration determined by radial immunodiffusion (r = 0.86, P less than 0.01), and showed good reproducibility (coefficient of variation 2.7%). On account of its simplicity and precision this functional assay should be of considerable use in evaluating hypercoagulability.


Diagnosis of alpha-thalassemia trait from Coulter Counter 'S' indices.

A number of patients of Mediterranean and Asian origins were found to have unexplained microcytic hypochromic red blood cells. Iron deficiency and beta-thalassaemia trait were both satisfactorily excluded in all of them. The haematological indices of these patients, obtained on a Coulter Model 'S' Counter, were found to be very similar to those seen in obligatory heterozygotes for alpha-thalassaemia. It is postulated that these patients were also carriers for alpha-thalassaemia. Subsequent investigation of some of these patients showed the characteristically reduced rates of alpha-chain synthesis seen in this condition. The discriminant function of England and Fraser (1973) may be of help in diagnosing this state. alpha-Thalassaemia trait should be considered in all patients of 'high-risk' ethnic origins with a blood picture suggestive of beta-thalassaemia trait but in whom the levels of Hb A2 and Hb F are within normal limits.


Pharmacokinetics of erythromycin on repetitive dosing.

Serum erythromycin concentration data from several repetitive dosing studies were analyzed with newly developed computer methods for fitting multiple-dose data and generating nonlinear least-squares estimates of pharmacokinetic parameters. This analysis indicates that the pharmacokinetics of erythromycin can be described by a one-compartment linear model with the following characteristics: (a) a lag time between the time of drug administration and the onset of absorption; (b) apparent zero-order rather than first-order absorption; (c) dose-to-dose variability in the rate and extent of absorption; and (d) day-to-day variability in the kinetics of elimination. The bioavailability of the third dose of erythromycin on a given day is considerably lower than that of the second dose or of the fourth and last dose of the day. The average apparent half-life of erythromycin was 1.8 hour on day 1 and 2.6 hours on day 3 of the repetitive dosing regimen.


Physiological identification and analysis of dentate granule cell responses to stimulation of the medial and lateral perforant pathways in the rat.

Stimulation of the dorsomedial or ventrolateral perforant pathways resulted in quantitatively different extracellularly recorded EPSPs in the fascia dentata of the rat. The two potentials differed in latency to peak and in width at half amplitude in a manner consistent with the different locus of termination of the two pathways on the granule cell dendrites. Both potentials were able to follow brief stimulus trains of 100 Hz, which suggests that they are monosynaptic. Medially elicited responses had their peak negativity approximately 100 to 180 micrometer deeper in the molecular layer than laterally elicited responses. Stimulation at short intervals along a dorsomedial to ventrolateral track in the angular bundle yielded a step function rather than a continuum of EPSP peak latency and half-width, in agreement with Hjorth-Simonsen's ('72) evidence for the separateness of the two pathways. Both pathways were able to induce granule cell discharge. Laterally elicited spikes, however, were delayed. Stimulation at intermediate locations frequently elicited double spikes from the granule cell population. Population spikes elicited by either pathway were inhibited for as long as 100 msec after a single discharge. Both pathways showed facilitation with double stimuli at short intervals, and both showed post-tetanic potentiation lasting at least 30 minutes. Under conditions where it could be shown that the two pathways at least partially converged onto the same granule cells, the response of one pathway did not increase when long lasting potentiation was induced on the other.


Some quantitative results on Golgi impregnated axons in rat visual cortex using a computer assisted video digitizer.

Axonal fiber distributions of pyramidal cells in the visual cortex of the albino rat have been investigated using the rapid Golgi method and modern data collecting techniques. Three dimensional coordinate information was extracted from Golgi-impregnated axonal networks using a computer-assisted video digitizer. Computer programs used this data to generate various statistical distributions. In particular, angular distributions of the initial collateral segments and their endpoints were examined and found to reveal anisotropies. Inspection of the spatial distributions of the endpoints indicated a clustering at two distinct levels with respect to the pyramidal cell from which they originate. Dynamic graphic displays of the three dimensional data have been obtained and presented in the form of computer tracings of various orthogonal projections.


The pigmented-rat optic nerve: fibre count and fibre diameter spectrum.

A well distributed electron microscopic sample of 52,000 fibres from the pigmented rat optic nerve cross section indicates a total count of 120,000 +/- 1,600 (S.E.M.) fibres ranging from 0.437 mu to 5.2 mu in diameter. The fibre diameter spectrum is essentially unimodal with a peak at 1.0 mu with a well developed "tail." These results are identical to those available in the literature for the albino rat.


A histochemical study of the innervation of cerebral blood vessels in the turtle.

Specific histochemical techniques for the demonstration of noradrenaline and of acetylcholinesterase have been used to study the distribution of adrenergic and cholinergic nerves to the cerebral blood vessels of turtle, Geoclemys reevesii. The major and medium-sized cerebral arteries were supplied with dense adrenergic nerve plexuses, the plexuses were particularly dense in the medium-sized pial arteries of very thick vascular wall, indicating the functional significance of these arteries in the cerebral circulation. The parenchymal arterioles and capillaries were also supplied with adrenergic nerves. On the other hand, the cholinergic innervation was less dense than the adrenergic one and the acetylcholinesterase activity of the nerve fibres was remarkably weak. By contrast, the parenchymal small arterioles and capillaries exhibited heavy acetylcholinesterase activity on the vascular wall and, in addition, the capillaries were supplied with the well-stained acetylcholinesterase-positive nerve fibres. These fibres and also the adrenergic fibres associating with the capillaries appear to be of central origin. It is suggested that the cholinergic mechanisms in the parenchymal small vessels also play an important role in the cerebral circulation. The basophil leucocytes observed abundantly in the blood of turtle emitted an intensive greenish yellow fluorescence after formaldehyde gas-treatment.


Morphometric analysis of the effects of exenteration and enucleation on the development of third and sixth cranial nerves in the rat.

The effects on rat cranial nerve growth of removing various amounts of extraocular muscle was studied using morphometric techniques. Growth in the third cranial nerves was found to be severely retarded when most of the muscle tissue was removed. By contrast, removal of the eye alone, leaving extraocular muscles relatively intact, was found to have little or no effect on the subsequent growth of third and sixth cranial nerve fibers and of extraocular muscle fibers. This conclusion could be drawn only through the application of statistical methods which take into account several generally unrecognized facts: frequency distributions of axon circumference and myelin sheath thickness are highly variable from nerve to nerve even in normal rats, which often have more large fibers in left than in right nerves. The bimodal nature of peripheral nerve fiber distributions precludes the use of such parametric tests as the commonly and inappropriately used t-test, but a non-parametric test such as the Kolmogorov-Smirnov test, extensively used in these studies, is inadequate for data comprising several sets of distributions to be compared. The application of the analysis of variance to some of the data and the merits of the procedure are discussed.


Growth of the adult goldfish eye. II. Increase in retinal cell number.

The retinas of adult goldfish, one to four years of age, 4-23 cm in length, were examined with standard paraffin histology to determine if new cells were being added with growth. Retinal cell nuclei were counted and the area of the retina was measured. An analysis of cell densities in various regions throughout the retina showed that the cells are distributed nearly homogeneously. The density (No./mm2 of retinal surface) of ganglion cells, inner nuclear layer cells and cones decreases with growth, but the density of rods remains constant. Thus the rods account for a larger proportion of the cells in larger retinas; The total number of cells per retina increases: the ganglion cells from 60,000 to 350,000; the inner nuclear layer cells from 1,500,000 to 4,000,000; the cones from 250,000 to 1,400,000; the rods from 1,500,000 to 15,000,000. This increase in the number of retinal neurons implies the formation of even more new synapses, and suggests the adult goldfish retina as a model for both neuro- and synaptogenesis.


Growth of the adult goldfish eye. III. Source of the new retinal cells.

The manner in which new cells are added to the growing adult goldfish retina was examined using 3H-thymidine radioautography. Cell proliferation leading to the formation of neurons is restricted to the retinal margin at the ora terminalis. New retina is added in concentric rings, with slightly more growth dorsonasally. The rate of cell addition is variable, averaging 12,000 cells/day. These new cells account for about 20% of the total increase in retinal area; the remaining 80% is due to hypertrophy, or expansion, of the retina. In contrast to all of the other retinal cells, the rods do not appear to participate in the retinal expansion. This hypothesized immobility of the rods would create a shearing strain between the retinal layers resulting in a shift in their position relative to the other cells. Were they to maintain synaptic contacts with the same horizontal and bipolar cells, the rod axons would have to be elongated peripherally or the post-synaptic cell dendrites displaced centrally. Since neurons with this morphology have not been found in the goldfish retina, these observations suggest that the rods must be changing their synaptic connections as the retina grows.


Neurophysiology of Spastic, a behavior mutant of the mexican axoloti: altered vestibular projection to cerebellar auricle and area acoustico-lateralis.

The spastic mutant of Ambystoma mexicanum shows deficiencies in swimming coordination and equilibrium. Behavior "phenocopy" experiments done previously indicated that vestibular projections to cerebellum and hindbrain interneurons might be responsible for mutant behavior patterns. To test function in mutant vestibular projections, single unit recordings were carried out in the vestibulo-cerebellum (auricle) and hindbrain area acoustico-lateralis (AAY) of wild-type and mutant animals in response to natural vestibular stimulation. Vestibular unit types responding during longitudinal tilting or to sustained tilt were encountered in equal proportions in both animal types. However, mutants showed a significant increase in spontaneously active units in these areas indicating possible deficiencies in inhibitory circuitry. In addition, the topographic location of vestibular units changed under the influence of the spastic gene. In mutants, significant numbers of units were found "translocated" into a ventro-caudal auricular zone abutting the AAL. Anatomical studies detailed in the following paper have shown this same area to contain grossly "translocated" cerebellar cells and afferent fiber tracts in mutants. These data are drawn together in a model in which deficiencies in the (form and) inhibitory function of the vestibulo-cerebellum is postulated to underly the behavioral abnormalities of the spastic phenotype.


Neuroanatomy of Spastic, a behavior mutant of the mexican axoloti: Purkinje cell distribution in the adult cerebellum.

The spastic mutant, found in the Mexican axolotl, shows swimming coordination and equilibrium deficiencies. Histological analyses of wild-type and spastic mutant cerebella previously characterized in physiological studies revealed changes in Purkinje cell location in the mutant auricle or vestibulo-cerebellum. Purkinje cells are "translocated" ventrally correlated with a similar translocation of vestibular single units described previuosly (Ide, '77). Where wild-type Purkinje cells are distributed from the surface to a depth of 250 micrometers, mutant Purkinje cells are "crowded" between 250 and 350 micrometers. Although mutant granule cells are present, boundaries between granule cell and Purkinje cell zones are less precise in mutants. Cerebellar nucleus cells are translocated medially, failing to organize into the discrete cell group appearing in wild-type. Cerebellar white matter tracts and fibers show changes, both in orientation with respect to the underlying tegmentum, and in fascicular organization. Obvious changes in the gross anatomy of the cerebellum are confirmed in reconstructions which define cell and fiber translocation. Thus, the spastic gene is compatible with differentiation of all cerebellar elements, but appears to alter interactions between cells, or between cells and the external milieu. Although all cell types are present in the mutant cerebellum, they fail to attain their proper positions along all three body axes.


Experimental analysis of embryogenesis of cerebellum in rat. I. Subnormal growth following x-ray irradiation on day 15 of gestation.

Rat embryos of 15 days gestation were exposed in utero to 170 R of X-ray irradiation. Embryos collected 6 hours, 1, 2 and 3 days after irradiation, and animals of 2, 6, 15 and 30 days postnatal age were used for this study. Six hours after irradiation cells in the neuroepithelium and mantle layer along the roof of fourth ventricle were observed destroyed. Neuroepithelium showed only fragmentary regeneration during next two days, and it contributed to a small number of Purkinje cells. During postnatal development of cerebellum the external granular layer, the zone of proliferative cells that gives rise to neurons of postnatal origin, was found reduced. Other structures such as internal granular layer, molecular layer and medullary layer also were reduced. These multiple temporally sequenced developmental events resulted in a subnormal-sized cerebellum. Various quantitative measures helped establish that grossly the cerebellum in the X-ray irradiated animals was about half of that in the normal animals. Problems related to regeneration in the embryonic cerebellum, and to the factors determining the subnormal size of the adult cerebellum are discussed. Viewing this as an experimental approach to the study of neuroembryogenesis of cerebellum, the role of Purkinje cells in the regulation of development of cerebellum is brought out.


Experimental analysis of embryogenesis of cerebellum in rat. II. Morphogenetic malformations following x-ray irradiation on day 18 of gestation.

Rat embryos of 18 days gestation were exposed in utero to 170 R of X-ray irradiation. Embryos were collected six hours, 1, 2, and 3 days after irradiation, and animals of 2-, 6-, 15- and 30-day-old postnatal age were sacrificed. Six hours after irradiation pyknosis of cells was notices in the external granular layer along the posterior aspect of the cerebellum. Neuroblasts, destined to differentiate into Purkinje cells, were found arrested in their migratory path. During subsequent periods of embryogenesis the external granular layer was found recovered, and clustering of the neuroblasts were disorganized and fragmented. This abnormal clustering of neuroblasts was permanent, and the external granular layer followed the same abnormal pattern in its growth. During postnatal development the internal granular layer also was found to follow the abnormal pattern of Purkinje cell layer. These abnormal developmental events were seen to lead to malformed folia in the anterior regions of the cerebellum. In addition to it the cerebellum of X-ray irradiated animals appeared smaller than the normal. Issues having a bearing on the differential radiosensitivity of different cells, factors determining the small size of the cerebellum, and cellular events determining the morphogenetic malformations are discussed.


Incorporation of 3H-fucose into nerve and glial cells: assessment by electron microscopic autoradiography.

Incorporation of 3H-fucose into hypothalamic tissue of rats was studied between ten minutes and seven days after intraventricular injection. In EM autoradiographs grain densities over perikarya of neurons, astro-, and oligodendroglia, and neuropil were evaluated. Grain densities were consistently higher over both types of glial cells as compared to neurons. The glia/neuron ratio was especially high after short experimental intervals and declined with increasing time intervals. Concomitantly there was an increase of grain density over the neuropil. The discussion concentrates on the methodical aspects which have to be considered in interpreting the autoradiographic data. It is concluded that both astroglia and oligodendroglia exhibit a considerably higher synthesis rate of glycoproteins per unit volume than nerve cells. The implications of the results for the interpretation of biochemical data on glycoprotein metabolism of brain tissue are discussed.


Traumatic alopecia in trichotillomania: a pathogenic interpretation of histologic lesions in the pilosebaceous unit.

Ten patients with traumatic alopecia (trichotillomania) were being investigated histologically and, in five of them, hairs from the affected scalp area were plucked out for direct microscopic examination. Some histologic features appear to be specific markers for traumatic alopecia: empty hair ducts, plucked out hair bulbs, clefts in hair matrix, catagen involution of empty outer root sheaths, Miescher's trichomalacia in the deep dermis and torn-off sebaceous glands. Other signs are unspecific, such as presence of catagen and anagen VI hairs, infundibular plugging, melanin in keratin plugs and in the dermal papilla. The relative frequency of the different histopathologic features was evaluated. When little clinical information is available, a diagnosis of traumatic alopecia can be supported by skin biopsy. The histologic picture of trichotillomania is always incomplete, depending upon factors such as intensity of pulling or/and time of biopsy after plucking.


Light and electron microscopy of excoriated psoriatic lesions in patients during topical treatment.

This is a light- and electron-microscopic study of excoriated, recalcitrant psoriatic lesions in ambulatory patients undergoing topical treatment. During regeneration of a stratum corneum without scales, in areas showing excoriations bounded by a non-cornified epidermis, horny  cell layers, designated I and II, are formed. In areas in which excoriations are delimited by an epidermis with a retained stratum corneum, the latter is composed of a horny cell layer I and/or II or III. The horny cell layers differ, as shown by light- and electron-microscopy. In the less fresh excoriations, a homogeneous substance, which includes fibrin deposits, is observed. This substance is also seen frequently in the stratum corneum. In the less fresh excoriations and in the stratum corneum there are numerous polymorphonuclear leukocytes. In these locations, however, they are only found simultaneously with the homogeneous substance containing fibrin deposits. Polymorphonuclear leukocytes are also seen in the dermal papillae and in the non-cornified epidermis, particularly in the macroscopically "old" excoriations. The changes observed in these recalcitrant lesions have been interpreted as secondary and are believed to be expressions of a non-specific reaction to the mechanical damage to which the ambulatory patients have constantly exposed the lesions. They are not interpreted as changes in the psoriatic condition per se.


Trichoadenoma of Nikolowski.

Trichoadenoma of Nikolowski is a rare benign tumor of the skin with hair follicle-like direction of differentiation. This tumor is less mature than trichofolliculoma and more differentiated than trichoepithelioma. Probably because of its rarity it has not been a well recognized tumor. We are reporting on eight cases of trichoadenoma to further define this benign growth.


Granuloma annulare with transfollicular perforation.

In recent years the phenomenon of transepithelial elimination has been found to be the underlying mechanism in a variety of skin disorders. "Perforating dermatoses" may show transepidermal or transfollicular elimination or a combination of the two. A case of papular granuloma annulare is reported, where in one lesion the pilary apparatus actively participated in the elimination of necrobiotic collagen from the dermis. To our knowledge, perforating granuloma annulare with a transfollicular pathway has not previously been described. Also, a classification of perforating dermatoses is presented.


Lymphoma of the skin. A comparative clinico-pathologic study of 50 cases including mycosis fungoides and primary and secondary cutaneous lymphoma.

A clinico-pathologic study of lymphomas of the skin included 14 cases of mycosis fungoides, 14 of primary lymphoma and 22 of secondary lymphoma. Mycosis fungoides has clinical and histopathologic features which allow for separation from the other groups. In this study, patients with mycosis fungoides had a longer duration of history and presented with papules, plaques, erythroderma or generalized dermatitis but not with tumor nodules ab initio. A confident histologic diagnosis required the presence of the mycosis cell, which was usually present in association with a mixed inflammatory cell infiltrate. Another important histologic feature was the presence of invasion of the epidermis by the mycosis cells singly and/or in nests (Pautrier microabscesses). Primary and secondary lymphomas of the skin presented clinically as multiple tumor nodules and histologically as a monomorphic infiltrate of neoplastic cells confined to the dermis and subcutis. A feature which has not been adequately documented in a large series was the presence of an associated prominent epithelioid cell reaction in several cases from all three groups.


Granuloma faciale. Ultrastructural study of three cases.

Light and electron microscopic observations were carried out in three cases of granuloma faciale. The dense granulomatous infiltrate of the corium showed: 1) more eosinophils than suspected by light microscopy, most of them with degenerative changes; 2) Charcot-Leyden chrystals; 3) numerous large histiocytes with their cytoplasms filled with lysosomal vesicles containing various inclusions (lamellar figures, myelin bodies, circular concentric organelles, digested membrane structures). The lack of Langerhans granules in dermal cells seems a valid reason to differentiate granuloma faciale from eosinophilic granuloma of the skin, usually considered a variety of histiocytosis X. No evidence of bacterial or viral infections was noticed. Granuloma faciale, despite its uncertain etiology, seems to represent a true entity.


Sebaceous carcinoma of the eyelid with Pagetoid involvement of the bulbar and palpebral conjunctiva.

A case of sebaceous carcinoma with pagetoid involvement of the palpebral and bulbar conjunctival epithelium was studied by light and electron microscopy. Ultrastructurally the neoplastic cells within the conjunctival epithelium were identical to those in the underlying invasive sebaceous carcinoma. Evidence of gradual transformation of conjunctival epithelial cells to the neoplastic sebaceous cells or transitional forms between conjunctival epithelial cells and sebaceous cells was not encountered. The evidence thus supports the theory that the neoplastic cells in the conjunctival epithelium are the result of secondary invasion by the underlying sebaceous carcinoma.


The use of the cryostat for histographic surgery.

Microscopically monitored excision for the treatment of skin cancer is becoming increasingly popular among dermatologists. One decision faced by beginning histographic surgeons involves the choice of apparatus for making the frozen sections. This paper compares the freezing microtome with the cryostat and gives details of the University of Iowa method, which employs the Slee cryostat.


5-Hydroxytryptamine-induced tachyphylaxis of the molluscan heart and concomitant desensitization of adenylate cyclase.

High concentrations of 5-hydroxytryptamine (5HT) first excite the isolated ventricle of Mercenaria mercenaria and then specifically desensitize it to further additions of the neuropeptide. This 5HT-induced tachyphylaxis is paralleled by a 5HT-specific desensitization of the myocardial adenylate cyclase and a decrease in intracellular cyclic AMP. However, FMRF-NH2, a cardioexcitatory tetrapeptide, can still increase contractility, cyclic AMP, and the adenylate cyclase activity of a tachyphylactic ventricle. These results are consistent with the hypothesis that 5HT augments molluscan myocardial contractility by elevating intracellular cyclic AMP.


Sodium and chloride in cows' drinking water and freezing point of milk.

The study was in two dairying regions of British Columbia, Canada, 700 Holstein-Friesian cows in 10 herds, to examine sodium and chloride in the drinking water of cows and to relate these to the composition of milk and to its freezing point. The Peace River had more sodium and more variation between herds in natural water supplies, which usually derive from surface dugouts, whereas the Fraser Valley region draws its water from mountain reservoirs. There were associated differences in the sodium content of milk between the two regions. These did not result in any regional differences in the freezing point of milk and there were no detectable changes in the chloride and lactose contents of milk to compensate for the higher sodium. The relationships between concentrations of milk lactose and milk chloride on the one hand and milk freezing point variations on the other were as expected.


Effects of dietary fluoride ingestion on ration intake and milk production.

The influence of 1-mo ingestion of a ration containing 50, 100, 150, or 200 ppm fluoride (as sodium fluoride) on milk production and ration intake of Holstein cows was studied. The total amount of fluoride administered was mixed into the grain mix and fed twice each day. The concentrations of fluoride in plasma and urine were related to the concentration of fluoride in the ration. There was no effect of fluoride on hay intake, but there was a decrease in intake of the grain mix at an intake of 200 ppm fluoride. The ingestion of 150 or 200 ppm fluoride for 1 mo had a slight adverse effect on milk production. From these results we suggest that rations containing less than 150 ppm fluoride will not influence ration intake or milk production adversely if they are fed for a short time to mature cattle not suffering from other long-term adverse effects of fluoride ingestion.


Effect of repeated inseminations with egg yolk semen extender on fertility in cattle.

Experiments were designed to determine if repeated inseminations of egg yolk diluent containing no semen would induce antibodies against egg yolk and would have an adverse effect on subsequent fertility under routine conditions of artificial insemination. Extender containing antibiotics polymyxin, dihydrostreptomycin, and penicillin and the enzyme beta amylase, with or without hen's egg yolk, was inseminated three to four times into virgin dairy heifers. The heifers subsequently were bred with bovine semen suspended in the extender containing egg yolk. Antibodies against antigens in the egg yolk extenders were not detected by complement fixation and agar gel immuno-diffusion, either in blood serum or in whole and homogenized cervical mucus taken before and after the repeat inseminations. Allergic reactions to the semen extender were not observed in any of the heifers. Calving rate from one service was 63.6% (7/11) for controls, 68.2% (15/22) after prior inseminations with egg yolk extender, and 69.2% (9/13) after prior inseminations with extender minus egg yolk. Under routine conditions of artificial insemination three to four exposures to extenders with or without egg yolk did not affect subsequent fertility adversely.


Trace minerals in cottage cheese.

The trace minerals, iron, zinc, copper, and manganese were determined in cottage cheese curd by flameless atomic absorption. Larger curd size, added calcium chloride, and fewer washes increased the iron and zinc content in the curd.


Persistence of antibiotics in milk from cows treated late in the dry period.

Nineteen cows were treated via intramammary infusion at various times prior to calving with one of two dry cow antibiotic preparations (cloxacillin or penicillin). Milk samples from these cows after calving were analyzed for antibiotic residues by the Sarcina lutea cylinder plate method. Eight cows were treated with cloxacillin was detected in the milk of only two cows after calving and then for only one milking, so no problem should exist with cloxacillin if the manufacturer's recommendations are followed. Penicillin residues were not detected in milk samples taken from cows treated more than 9 days prior to calving with the dry cow penicillin preparation. However, seven of nine cows treated with penicillin up to 9 days prior to calving had detectable penicillin residues in the milk from treated quarters after calving. Only one cow had detectable penicillin residues longer than the manufacturer's recommended milk withholding time of 96 h, and this cow was treated only 3 days prior to parturition. Normal routine on a dairy farm and adherence to manufacturer's recommendations should result in no antibiotic residue problems in milk from cows treated during the dry period for mastitis control with either cloxacillin or penicillin.


Partial enzymatic hydrolysis of whey protein by trypsin.

Partial enzymatic hydrolysis of whey protein by trypsin increased solubility of this protein in water. Water-insoluble, heat-denaturated whey protein was solubilized fully by trypsinization. Optimal conditions for the enzyme reaction, established by the pH-stat technique, were: digestion at pH 8.0 and 55 C for approximately 3 h, at an enzyme-substrate ratio of 1 : 100. Under these conditions, 500 mumoles of titratable protons were liberated per g of substrate in the course of the reaction. Digestion at 40 C generated only about 400 mumoles of acid. Predenaturation of the substrate by heat did not improve digestibility. The extent of hydrolysis reached approximately 8% of all peptide bonds in the protein. Fractionation of the digest on Sephadex G-50 showed it was composed of a major fraction of highly water soluble peptides, ranging in molecular weight from approximately 500 to 5000. The gel excluded a minor fraction of larger, aggregated peptides. This aggregate was dissociated in the presence of urea and a reducing agent. All amino acids in the digest, except some lysine and arginine, were peptide bound.


Development of and fluid accumulation in mammary glands of freemartins administered estradiol, estrone, or testosterone..

Eighteen Holstein freemartins acquired at 1 wk of age were assigned to a control and to four treatment groups, but only two of the groups received hormone the first 50 wk. Testosterone administered for the first 50 wk appeared to inhibit teat growth whereas estrone stimulated teat and udder length. At 50 wk of age, implants releasing daily approximately 12.9 microgram of testosterone, 2.9 microgram of estrone, or 2.6 microgram of estradiol-17beta per kg of body weight were implanted for 6 wk. One of three testosterone-treated and 9 of 11 estrogen-treated animals exhibited increased udder development associated with fluid accumulation. The 10 animals with fluid accumulation in the udders were milked once 39 days after implanting. The fluid contained 15.0% total solids, 4.1% fat, and 7.0% protein, values which are between those for normal milk and colostrum. These studies support the concept that administration of low concentrations of estrogens alone, released continuously from implants, were capable of stimulating fluid secretion in mammary glands of animals that had no detectable gonadal luteal tissue.


Protein for calves on a limited milk-early weaning system.

Complete pelleted calf starter rations were fed to Holstein heifer calves on a limited milk-early weaning program from 3 days to 12 wk of age. Five rations fed to each of 10 calves were to contain crude protein percentages of 10, 12.5, 12.5 with 97% urea, 15, and 15 with 1.1% urea (as fed). The digestible protein:digestible energy ratios (g digestible protein/Mcal digestible energy) of the rations (in same order) were 23.4, 30.7, 28.8, 36.4, and 41.5. Average birth weight was 42.9 kg and weaning weight at 4 wk, 52.8 kg. Treatment effects on feed intake, average daily gain, and feed efficiency were analyzed after adjustment of birth weight and removal of effects of block and location. Feed intake for 12 wk was greater for 15% crude protein with 1.1% urea than for either 12.5% ration but not different from 10% protein. Average daily gain was increased for 15% protein rations compared to 10 or 12.5% protein. Gain by claves fed 10% protein was equal to that by those fed 12.5% protein. Feed efficiency during wk 5 to 12 was improved for 15% with vegetable protein compared to 10% crude protein or the 12.5% crude protein ration with vegetable protein. There were no differences in intake, gain, or efficiency between urea and vegetable protein.


Effects of package, extender, and light on stored frozen bull spermatozoa.

Spermatozoa were analyzed when fresh, freshly frozen, and stored at --196 C for 6 and 18 mo after processing in egg yolk-citrate and Promine-D extender with varying exposure to light and packaging in straws or glass ampules. Over all treatments there were decreases with time in spermatozoal motility, oxygen uptake, and cellular glutamic oxaloacetic transaminase due to freezing-thawing. Percent progressive motility decreased from spermatozoa freshly frozen (36.5%) to those stored for 6 mo (33.6%). Oxygen uptake in freshly frozen samples was 8.4 microliter per 10(8) cells per h. In frozen semen stored for 6 and 18 mo corresponding values were 12.2 and 8.3 microliter. Packaging methods did not have a significant effect on oxygen uptake, but package interacted with storage. Egg yolk-citrate extender supported greater progressive spermatoal motility than did promine-D. Extender interacted with storage for all criteria. Visible light radiation reduced progressive spermatozoal motility from 40.2 to 38.0% and oxygen uptake from 11.8 to 10.8 microliter per 10(8) cells per h. Light interacted with storage time. Correlations between all criteria and storage times were not important practically.


An indirect method of forming expressions for the inverses of genetic variance-covariance matrices for two traits.

Pratical application of best linear unbiased prediction procedures to large data sets requires efficient use of computer time and storage. One way to increase effiency of computer use is to eliminate extraneous equations, i.e., equations for genetic predictions that are of no or little practical value. Rules are derived for obtaining, by inspection of the pedigree, a matrix representing the inverse of the genetic variance-convariance matrix for two traits in which all genetic values are not represented. The need to form the genetic variance-covariance matrix itself is eliminated. The condition in which the expression is the exact inverse is specified. An illustration is provided. Inbreeding is not considered.


Solitary autonomous thyroid nodules: comparison of fluorescent and pertechnetate imaging.

Twelve patients with solitary autonomous thyroid nodules were scanned with [99mTc] pertechnetate and by fluorescent imaging. Nodular dimensions were essentially identical on the two types of scans, but the relative scan densities in the nodular versus extranodular areas demonstrated striking differences. In 11 of the 12 patients, the ratio of nodular-to-extranodular radiotracer accumulation was significantly higher than the ratio of nodular-to-extranodular iodine content. In two patients with no demonstrable extranodular radiotracer accumulation by initial pertechnetate scan, extra-nodular tissue was demonstrated by fluorescent imaging. In such cases, fluorescent scanning may eliminate the need for a second radionuclide scan following TSH stimulation to visualize the extranodular tissue. Fluorescent scanning offers a unique new method for aiding the evaluation of patients with suspected autonomous nodules, and can facilitate the diagnosis in some cases. The maintenance of relatively uniform iodine concentration between nodular and extranodular tissues is an intriguing finding that bears further investigation.


Improved method for quantitative bone scanning.

A quantitative gamma-camera technique is used to calculate the percentage of administered activity taken up by various areas of the skeleton. The method uses an external standard source of activity as a reference, and in addition presents the information in a new format, the Organ Uptake Image (OUI). Two cases of Paget's disease serve to illustrate the usefulness of this approach to quantitative bone imaging.


Evaluation of gastro-pulmonary aspiration by a radioactive technique: concise communication.

Seven selected patients were given 3-5 mCi of Tc-99m sulfur colloid orally at bedtime and the lungs were imaged in the morning. Two showed definite evidence of aspiration and one suggestive evidence. This is a simple, non-invasive method of demonstrating pulmonary aspiration of gastric contents.


Scintiphotography of lungs with dry aerosol--generation and delivery system: concise communication.

A compressed-air nebulizer with low holdup and high output was used to nebulize [99mTc] pertechnetate presented in normal saline. Generated droplets were dried in line and led to an inhalation chamber from which the dry aerosol was inhaled using a nose or mouth inhalation unit. The mass median diameter of the particles was 0.8 microns, with an associated geometric standard deviation of 2.0. The deep lung delivery efficiency--defined as the ratio of the activity deposited in the lung area to the activity nebulized--was found to be reproducible and consistent (15-22%) in all the subjects studied. A 3-5 min inhalation of aerosol, nebulized from 20 mCi, was sufficient to provide a lung image of good information density. No noticeable deposit was seen in the trachea or major brochi. The system is inexpensive, stable in performance, adaptable to other solutions or colloids, and is promising for routine use.


Skeletal and reticuloendothelial imaging in osteopetrosis: case report.

Skeletal and reticuloendothelial images, using Tc-99m HEDP and Tc-99m sulfur colloid respectively, were obtained from two adult patients with osteopetrosis. Skeletal images demonstrated increased activity in multiple fracture sites, in mandibular osteomyelitis, in ends of splayed long bones adjacent to joints, and in the epiphyseal ends of short tubular bones. The remainder of the skeleton involved with osteopetrosis showed no generalized increased uptake of Tc-99m HEDP. These findings indicate that metabolic activity in this disease is abnormally increased in the usual areas of bone growth but appears normal elsewhere. Reticuloendothelial imaging showed an almost total lack of activity in the axial and peripheral skeletal marrow space. Anemia, however, was only moderate in these patients. Skeletal scintigraphy may be useful to evaluate the presence and extent of the frequent complications of osteopetrosis, namely fractures and osteomyelitis.


Parathyroid adenoma imaged by Ga-67 citrate scintigraphy: case report.

A preoperative Ga-67 citrate scan showed abnormal uptake in a patient with a cervical mass that subsequently proved to be a predominantly oxyphilic parathyroid adenoma.


Charge and nature of technetium species produced in the reduction of pertechnetate by stannous ion.

By using a cation-exchange distribution technique, the net charge of the technetium species produced in the reduction of pertechnetate by stannous ion at ph less than or equal to 2 had been determined to be + 2. The species carrying this charge is either the dihydroxy technetate (Tc(OH)2(2)+) ion or the oxotechnetate (TcO2+) ion. These species are hydrolysed to technetium dioxide dihydrate (TcO2 - 2H2O) at higher pH.The advantage of the ion-exchange distribution technique for these studies is that they can be done with carrier-free technetium rather than at the high concentrations required for the more conventional methods of ion-charge determination. The results, therefore, are more likely to be applicable to the situation existing in the routine preparation of Tc-99m radiopharmaceuticals.


A model for local accumulation of bone imaging radiopharmaceuticals.

A simple models, having phenomenological parameters as variables, is developed for predicting local radioactive tracer accumulation in bone. Blood delivering tracer to one gram of bone is treated as a compartment separate from the remainder of the circulation in order to observe the effects produced by variations in both bone flow and barrier permeability. Kinetic curves derived by analog computer were obtained for normal and perturbed values of the parameters for F-18 and Ca-47 in a segment of rabbit bone. Apparent confirmation of the predicted influence of decreased blood flow on F-18 deposition was obtained by measuring bone uptake following constriction of the right femoral artery in five rabbits. Such models may prove useful in explaining variations in uptake for different agents, in selecting imaging times, and in correlating uptake patterns with disease.


Radiation damage to mouse testis cells from [99mTc] pertechnetate.

The radiation dose and the biologic damage to mouse testis from intravenously administered [99mTc] pertechnetate were studied. The dose was measured for penetrating radiations from Tc-99m, using calibrated thermoluminescent dosimeters and calculations from the uptake of the nuclide in the testis, and was found to be 4.9 rada per mCi of Tc-99. The biologic damage was measured by the decrease in the number of sperm heads in the testis, counted both by hemacytometer and by Coulter counter. In preliminary experiments using external gamma radiation from Cs-137, the number of sperm heads reached a minimum 29 days after irradiation. Twenty-nine days after injection of 5.8 mCi of Tc-99m, which gives 28 rads to the testis, the number of sperm hads decreased to 70% of control. The biologic effect corresponds to that seen after 40 rads of gamma radiation from Cs-137. The damage to mouse testis cells from internally administered Tc-99m as measured in an in vivo system appears to be at least as significant as that from external gamma irradiation, if not more so.


Improvement in visualization of hepatic lesions with upright views.

Standing scintiphoto views of the liver may provide improved visualization as compared with conventional supine liver images. This is partially due to decreased respiratory motion of the liver. The standing position is recommended if the supine liver scan appears normal in a patient suspected of metastatic disease.


Intermodulation product pair 2f1 +/- fh: masking and growth.

To examine the question of whether the distortion product 2f1 - fh is unique--whether a special nonlinear mechanism is responsible for its production--estimates of 2f1 - fh and of 2f1 + fh amplitudes were obtained in three listeners. Threshold shifts measured with a tone-on-tone masking paradigm for each distortion product suggest that each have similar properties and are masked by other tones as if they had a physical realization in the cochlea. Their masking is not a function of stimulus fine-time structure. The 1 dB/dB growth of 2f1 - fh was not changed by rendering it inaudible as previously suggested. Possible explanations of the 1 dB/dB growth of 2f1 - fh compared with the accelerated growth of 2f1 + fh are examined.


Intensity perception. VIII. Loudness comparisons between different types of stimuli.

In this paper, we describe an extension of our preliminary theory of intensity resolution [Durlach and Braida, J. Acoust. Soc. Am. 46, 372-383 (1969)] to include loudness comparisons among different types of stimuli. The extended theory relates mean loudness matches to discrimination and provides a framework for the interpretation of results on the intrasubject variability of loudness comparisons. The predicted relation between mean loudness matches and discrimination is essentially the same as that proposed by Riesz [J. Acoust. Soc. Am. 5, 211-216 (1933)]. With regard to the variability of loudness comparisons, the extended model is essentially the same as the preliminary model except that a new term is included in the trace-mode memory variance to account for the dissimilarity of the stimuli being compared. The model is compared to some published data on loudness matching and discrimination and to some new data of our own on the variability of loudness comparisons obtained in a two-interval, roving-level, loudness-discrimination experiment.


Behavioral system and apparatus for tone-detection and choice reaction times in the cat.

An efficacious operant-conditioning procedure for psychophysical experiments with cats is described. The system features (a) restraint of the cat and the use of the liquid reinforcement delivery cup to control orientation with respect to the stimuli, (b) a minimum of apparatus between the cat and a free-field sound source, (c) two response pedals so that separate "Yes" and "No" responses are defined, (d) a discrete trial procedure with reaction time (RT) defined as the time from the onset of a trial until the occurrence of a response, and (e) an effective liquid reinforcer and simple delivery system. Operation of the system was demonstrated with the method of constant stimuli. Detectability was directly related, and median RT for correct "Yes" responses inversely related, to tone sound pressure.


Moderate frequency compression for the moderately hearing impaired.

The intelligibility of frequency-compressed speech was measured for four normal and eight hearing-impaired subjects with sensory-neural high-frequency loss. Hearing levels were roughly 40 dB. Four conditions of frequency compression, 0%, 20%, 33%, and 55% were obtained using a Varispeech compressor. The test materials were PB-50 word lists recorded by one male and one female speaker. The effect of frequency compression was to reduce intelligibility in all cases except one, that of the female speaker at 20% frequency compression. For this case, the hearing-impaired listeners showed a small average improvement. Although the effect was small, it represents one of the few instances when an experimental evaluation of a frequency-compression system has yielded positive results with the hearing impaired.


Processing of phonemes in speech: a speed-accuracy study.

The present study investigated the serial or parallel processing of phenemes within a syllable. Subjects were required to press a key, on cue, to indicate whether two successive, binaural CVC syllables were the same or different. The cue was a tone which occurred at varying times after the onset of the second CVC and often interrupted its presentation. Subjects' accuracy as a function of time was compared for discriminations involving the first, second, and third phonemes. The results show that information about the phonemes within a CVC syllable is accruing simultaneously. The importance of these results for models of speech perception is discussed.


Pitch ratings of harmonic series.

When the components of a harmonic series are of equal amplitude, pitch ratings are determined almost exclusively by the fundamental frequency of the series. Only by extreme modification of the amplitudes of the several components was it possible to modify the pitch ratings assigned to the harmonic series in a direction opposite to that determined by the fundamental frequency.


Panic-fear in asthma: requests for as-needed medications in relation to pulmonary function measurements.

Requests for as-needed medications and treatments (PRNs) by asthmatic patients scoring high, moderate, or low on the Asthma Symptom Checklist panic-fear category were studied for days when patients were matched at normal, intermediate, and subnormal levels of pulmonary function. Low panic-fear patients were the least likely to request PRNs regardless of the pulmonary function level. In contrast, high panic-fear patients often requested PRNs each level of pulmonary function. Only moderate panic-fear patients made progressively more PRN requests on days when pulmonary functions were lower. These observations and others concerning the adverse influence of extreme panic-feat coping styles upon the treatment of asthma were discussed.


What should be optometry's role? How should we prepare for it?

This is a position paper which broadly states the role which, in the author's opinion, optometry should adopt as its goal and the educational environment in which we can best prepare graduates to fulfill that role. The role briefly stated, is that of first contact supplier of vision care and of certain aspects of primary health care. The appropriate educational milieu is held to be the academic health center.


Optometric goals and priorities.

An analysis of the needs of the public for optometric services by (1) the examination of the epidemiology of vision problems, (2) a systems analysis of the vision care system, (3) the services optometrists provide and (4) the educational resources available, indicate that the priorities for optometric development should be on primary vision care services and new academic facilities.


Leadership and change in optometric education.

The quality of institutional administration and the competence of its academic leaders are considered to be crucial elements in the continued progress of optometric education. Educational leadership to meet the need for ongoing, guided, systematic educational planning is underscored. Such planning, in turn, depends significantly on the emerging role definition of the optometrist as a primary care practitioner.


Financing of optometric education.

Decline in enrollments in college age group is reflected in health professional and law schools. This evolving reduction in applicant pool is discussed with reference to caused factors and contrasted with the post World War II boom. These factors are discussed in relationship to present and future fiscal integrity of our optometric colleges. The author illustrates the need for securing financial support from state governments for existing optometric educational institutions before building new schools.


Education for the optometric educator.

Optometric education is faced with the need for new thinking in developing and training educators and new methods of financing their education. Establishing of research faculty and the instituting of research in present schools of optometry must be given a high priority in the future of optometric education.


Methodology for interfacing results of basic science research and clinical practice.

The importance of the integration of basic vision sciences and applied clinical research is discussed. Steps which must be taken in optometry and in the schools and colleges in particular are reviewed. Some of the problems that will be encountered are discussed.


Quality is still the backbone of good education.

The author believes that quality optometric education results from excellent teaching, which depends on qualified faculty members who also add to optometric knowledge through research, and on a curriculum that stresses fundamentals. He believes that practicing optometrists can help to encourage and assist research.


Continuing optometric education crossroads.

This paper gives a brief overview of continuing optometric education from the perspective of the providers and the Commission on Continuing Education. The early history is covered as well as a discussion of some present problems and concerns of many of the providers. This is followed by recommendations for the future and a proposed plan for each provider's involvement in continuing education.


The paraoptometric puzzle.

In the past ten years, interest in the production and utilization of paraoptometric personnel has risen sharply. Production alone will not meet the demands of the foreseeable future. More effective utilization of the skills of the trained paraoptometric is vital. Current practitioners have been slow to accept new modes of vision care delivery. Conversely, most optometric educational institutions have been unwilling or unable to develop training programs for student optometrists beyond the traditional solo concept. Recommendations are presented for immediate and long range remediation.


Prevention and enhancement: future needs.

The objective of prevention of eye and visual problems, and the objective of enhancement of vision performance are primary and most urgent for undergraduate, postgraduate and/or continuing optometric education. Prevention is something done before the need occurs. The concept of enhancement assumes performance far beyond so-called normals. The future needs of the public and the profession should determine the content and scope of optometric education pre and post graduation. Occupying the unique areas of prevention and enhancement can expand optometry's role, insure its continued growth and vital service to the public.


The optometric recognition award program--an option for self assessment.

This discussion addresses itself to the need for all optometrists to continue recognizing their professional responsibility to maintain continuing competency through meaningful optometric education experiences; and to work toward this goal by participation in the Optometric Recognition Award Program. The ORA Program is structured to enable the participant to design, record and fulfill his personal continuing optometric education needs. Fullfillment of the award requirements, 150 hours of C.O.E. in three years, results in recognition by the AOA in the form of a recognition plaque.


Age-dependent changes in the oxidative metabolism in rat brain.

The effects of aging on the oxidation of labeled glucose and 3-hydroxybutyrate and on several mitochondrial enzymes in rat brain were investigated. The oxidation of labeled glucose and labeled 3-hydroxybutyrate was diminished by about 40 and 35%, respectively, in cerebral cortex slices from 2-year-old rats compared to those from 3-mo-old animals. A significant reduction in the activities of 3-hydroxybutyrate dehydrogenase, 3-oxo acid CoA transferase, acetoacetyl CoA thiolase, and NAD-isocitrate dehydrogenase was observed in brains of 1- and 2-year-old rats compared to 3-mo-old animals. However, aging had no effect on the activities of citrate synthase and pyruvate carboxylase. These findings show that specific alterations occur in the activities of several mitochondrial enzymes in aging brain.


Quantitative and morphological changes in neurons and neuroglia in the indusium griseum of aging mice.

The indusium griseum was investigated quantitatively in 5-mo-old and 18-mo-old mice. There was no difference in the number of neurons between 5 and 18 mo, but the number of neuroglia increased by almost 30%. Astrocytes and microglia increased in number, but oligodendrocyte number remained unchanged. There was no significant variation in the volume density of neuronal perikaryon, neuropil, or blood vessels with age.


Isolated aortic valve stenosis in the eighth decade.

Aortic valve stenosis was evaluated in 26 patients in the eighth decade of life, representing 20% of all patients referred for aortic valve stenosis. There were no clinical features which distinguished this older group from younger patients. Coronary artery disease was present in 46% of the older group, 30% in the younger. Angina pectoris or an infarction pattern on the electrocardiogram was not useful in predicting coronary artery disease in either group. A dominant left coronary circulation was more frequent (22%) in the younger than the older group. This was related to the higher incidence of congenitally deformed aortic valves (55%) found in the younger, compared in the advanced age group (5%). The surgical mortality in the younger and advanced age group was 8 and 20%, respectively. Mortality in both groups was related in more than half the patients to coronary artery disease.


A factor analytic study of daydreaming, imaginal process, and temperament: a replication on an adult male life-span sample.

One hundred and seventy males aged 24 to 91 years were measured on daydreaming and related mental activity using the imaginal processes inventory and on temperament using the Guilford-Zimmerman Temperament Survey to determine if earlier results relating temperament to daydreaming in college populations were generalizable to the adult life-span. The earlier derived factor of "Neurotic-Anxious Absorption in Daydreaming" was found in this sample and had a negative correlation with chronological age, suggesting a decrease with increasing age. Other earlier derived factors on "Personal Acceptance-Utilization of Daydreaming," "Masculinity-Femininity," "Thinking Introversion," and "Social Extroversion" were also found in this sample, but were not related to age.


Changes in individual attitudes toward traditional morality: a 24-year follow-up study.

Changes in individual attitudes toward traditional morality are charted by focusing on a sample of 1950 persons from rural Pennsylvania surveyed as high school sophomores in 1947 and again 24 years later when they were in their early 40s. A series of 12 Likert-type items were used to assess traditionalism. In general, the subjects' attitudes changes toward a more permissive stance in regard to questions concerned with adult behavior. Liberalization of attitudes toward the behavior of young people was less pronounced. The direction and degree of change differed markedly among individuals. Frequency of church attendance was closely associated with the amount of change. Those attending church once a week or more were decidedly less likely to change toward a liberal or permissive position than were those who attended less often. Other factors related to amount of liberalization included residence, education, and income.


Sampling in social gerontology: a method of locating specialized populations.

This paper describes a two-stage sampling design for obtaining probability samples of the elderly and other specialized populations. The first stage enumerates a sample of elderly individuals residing in a probability, sample of households; the second stage involves the mailing of a questionnaire to the eligible respondents located in the first stage. The results of this method for a study of noninstitutionalized elderly in Washington State are reported. These results indicate that (1) elderly individuals will respond in the two-stage sampling design does not appear to increase sample bias above that expected in normal mailed-questionnaire studies, and (3) the method is extremely inexpensive. Use of the two-stage design by social gerontologists is recommended.


[Study of folic acid blood levels during estro-progestagen treatments].

When the blood levels of folates were estimated in 100 women following treatment with oestro-progestagens the following facts emerged : 1) There is no significant difference between the folate levels found in women on oestro-progestagens compared with a control population of the same age. 2) We have not found any evidence of frank folic acid deficiency in women on oestro-progestagens, but there have been slight drops in the levels of folates in women who show other reasons for folic acid deficiency than taking oral contraceptives. These are : troubles in absorption, salmonella, an increase in the need for folic acid in pregnancy, and failure of transport. Furthermore the incidence of lower levels in the control population was exactly the same as in the experimental population.