Liposomes: a new approach to gold therapy?

Gold sodium thiomalate (GST) can be encapsulated in egg phophatidyl choline (and cholesterol) vesicles. Leakage from vesicles at room temperature is negligible allowing storage for at least 6 days prior to use. Intravenous injection of GST encapsulated in egg phosphatidyl choline vesicles results in: 1) delayed blood clearance, 2) enhanced uptake by the liver and spleen, 3) reduced uptake by the kidney, 4) reduced 24 hr urine excretion, and 5) enhanced uptake by inflamed tissues compared to free GST given by the same route. Thus, our preliminary findings suggest that egg phosphatidyl choline vesicles may be a suitable carrier of GST for parenteral administration.


Metabolism and distribution of gold compounds.

The pharmacokinetics of gold in blood and urine are compared during intramuscular and oral chrysotherapy for rheumatoid arthritis. Blood gold levels are 3 to 10 fold higher with injectable aurothioglucose and gold sodium thiomalate (50 mg/week) than with oral auranofin (6 mg/day). But, the serum half-life of the parenteral compounds is significantly shorter (5.5 days) than the oral agent (14-21 days). The gold content of urine is nearly 10 times higher with the intramuscular compounds than with the oral drug. The excretory pathways and tissue distribution of gold during conventional intramuscular chrysotherapy are reviewed. Forty percent of a 50 mg injection of gold sodium thiomalate is excreted in 7 days, of which 70% is recovered in the urine. Highest gold concentrations are found in the reticuloendothelial system, adrenal glands and kidneys, while the bone marrow, liver, skin and bone contain the greatest quantities of gold.


The aurosome.

Aurosomes are lysosomal bodies containing gold. Colloidal gold produces aurosomes containing spherical electron-dense granules. Soluble gold salts produce aurosomes containing lamellar, filamentous and rod-like profiles studded with particles and granules. This morphological pattern is quite distinctive, and is not affected or altered by which particular soluble gold salt is administered, by which route it is administered or in which species or cell type the aurosome occurs. In the skin of patients treated with soluble gold salts the characteristics electron-dense formations indicating the presence of gold are often found in compound melanosomes and other lysosomes in the dermal macrophages; while in the synovial membrane these characteristic electron-dense deposits are seen in the numerous lysosomes that develop in the rheumatoid synovial membrane. Thus it would appear that while aurosomes may vary somewhat in morphology, the electron dense contents indicating the presence of gold have a fairly constant morphology.


Gold compounds in rheumatoid arthritis: clinical-pharmacokinetic correlates.

Currently available techniques do not enable the clinician to identify which patients with rheumatoid arthritis will respond favorably to chrysotherapy or to predict which patients will develop gold-related complications. Gold concentrations are similar in blood, urine, feces, skin, hair and nails in gold-responders and non-responders, and in gold-toxic and non-toxic patients. However, gold toxicity is a function of dosage schedule; higher than conventional doses increase the prevalence and severity of adverse reactions. Preliminary observations suggest that the frequency of common side-effects (e.g. dermatitis, stomatitis, proteinuria) from oral gold (auranofin) is less than that incurred with intramuscular gold prepartions. The possible genetic predisposition to develop gold toxicity is under investigation.


In vitro binding and pharmacokinetics of gold salts in plasma proteins and chelating agents.

The binding of sodium aurothiomalate, sodium aurothiosulphate and aurothioglucose to plasma proteins has been  investigated in vitro. All gold compounds were bound to protein at a similar rate and had similar apparent affinity constants and binding capacities. Penicillamine (10 or 100 microgram/ml) was unable to chelate significant amounts of bound gold from plasma protein.


Immunopharmacology of auranofin and gold sodium thiomalate: effects on humoral immunity.

The effect of auranofin and gold sodium thiomalate (GST) on antibody production was evaluted using antibody-dependent cellular cytotoxicity and complement-dependent antibody responses to sheep red blood cells (SRBC) and L929 fibroblasts. The results indicated that auranofin was capable of depressing antibody production to L929 cells, but inconsistently depressed the response to SRBC in the mouse. GST, however, stimulated both responses. In vitro, both compounds inhibit secretion of antibody. These results demonstrate that auranofin, in contrast to GST, is capable of suppressing humoral immunity which may explain its more rapid effect on immunological parameters in RA.


Effect of chrysotherapy on parameters of immune response.

Thirty-nine subjects with classical or definite rheumatoid arthritis received weekly intramuscular gold sodium thiomalate (GST) to sustain gold blood levels of more than 320 microgram/dl. Statistical analysis revealed significant declines from pre-treatment values for IgM, IgG, and IaA. Rheumatoid factor titer decreased in 29 of 39 subjects, 15 becoming seronegative. Circulating lymphocytes decreased by 27%. The maximal suppressive effect on IgM was not achieved until the 3rd and 4th years of GST administration. Auranofin (AF) 6 mg/day was administered to 15 patients for an average interval of 45 weeks. In vitro and in vivo suppression of lymphocyte mitogen response with AF was more rapid in onset and significantly greater than with GST. Suppression of dinitrochlorobenzene skin sensitization was observed in AF patients. The clinical response in GST treated subjects correlated with suppression of immunoglobulins, rheumatoid factor titer, and circulating lymphocytes. A significant decline in these variables was not achieved for a corresponding interval with AF treatment. It is suggested that chrysotherapy may be applied more widely to immunologically-mediated disorders and perhaps be used to affect selectively B versus T mediated dysfunction.


Effect of gold salts on adherent mononuclear cells in tissue culture.

Adherent mononuclear cells from normals and patients with rheumatoid arthritis (RA) were isolated and effects of gold salts on cell cultures assessed in vitro. Phagocytic function of adherent mononuclear cells was assessed by the injestion of opsonized chicken red blood cells. Absolute numbers of phagocytic cells were higher in the RA patients than normals. Gold salts in concentrations 0.5-5.0 microgram/ml significantly reduced the numbers of both adherent and phagocytic cells when compared to control cultures. This suppression was particularily marked in the RA patients and was dose and time dependent. However, mononuclear cells surviving incubation with gold salts appeared to maintain phagocytic function in similar proportions to control cultures.


Antimalarials. 11. Synthesis of 3- and 5-aminoquinolines as potential antimalarials.

A series of 3-quinolinediamines (1g, 2c, and 3e) structurally related to primaquine and 4-methylprimaquine have been prepared and tested for antimalarial activity against Plasmodium berghei in mice and antileishmanial activity against Leishmania donovani in the hamster. All were inactive. In addition, three 5-quinolinediamines (4b, 5, and 6) were prepared. All were inactive against Leishmania donovani in hamsters. One of the examples, 6, was curative against Plasmodium cynmolgi in the rhesus monkey.


3-Phenyl-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]indole-2-carbonitrile, a potent inhibitor of prostaglandin synthetase and of platelet aggregation.

A number of indoles containing the 2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl side chain have been prepared by standard methods. Alternate, novel syntheses of indole-2-carboxamides and indole-2-carbonitriles have been developed. The title compound, 7e, was found to be a potent inhibitor of bovine prostaglandin synthetase in vitro and to lower serum prostaglandin levels after oral or intraperitoneal administration to rats. Consistent with prostaglandin synthetase inhibition, 7e prevented arachidonic acid induced diarrhea in mice and also collagen, ADP, or epinephrine induced platelet aggregation in human platelet-rich plasma. In contrast to many prostaglandin synthetase and platelet-aggregation inhibitors, 7e had neither ulcerogenicity nor systemic antiinflammatory activity in rats.


5-Fluoro-2'deoxyuridine 5'-(p-azidophenyl phosphate), a potential photoaffinity label of thymidylate synthetase.

5-Fluoro-2'-deoxyuridine 5'-(p-azidophenyl phosphate) (1), a potential photoaffinity labeling reagent for thymidylate synthetase from a methotrexate-resistant strain of Lactobacillus casei, has been synthesized and characterized. UV254 irradiation of mixtures of thymidylate synthetase with 1, containing 14C-labeled phenyl and 3H-labeled pyrimidine rings, in the presence of excess 5,10-methylenetetrahydrofolate, the cofactor for the reaction, produced two complexes, separable from the native enzyme by polyacrylamide gel electrophoresis, in which only the 3H-containing moiety was bound to the protein. When mixtures of enzyme and 1 were irradiated in the absence of cofactor, complexes separable from the native enzyme were not observed. However, the 14C-containing component of 1 was now bound to the protein in the absence of the 3H-containing portion. The results are discussed in terms of the topography of the enzyme active site.


Antifungal agents. 5. Chemical modification of antibiotics from Polyangium cellulosum var. fulvum. Alcohol, ketone, aldehyde, and oxime analogues of ambruticin.

Alcohol, ketone, aldehyde, and oxime analogues of ambruticin (1) were prepared. The analogues were tested against Histoplasma capsulatum, Microsporum fulvum, Candida albicans, and Streptococcus pyogenes. Structure-activity relationships are described. Increasing the bulk of substituent at C1 and C5 reduces antifungal activity.


Lysosomotropic agents. 1. Synthesis and cytotoxic action of lysosomotropic detergents.

Amines whose pK values lie between about 5 and 9 are lysosomotropic because lysosomes are acidic intracellular compartments. If such amines bear long hydrophobic chains, they become detergents upon protonation inside the lysosomes, rupturing the lysosomal membrane and killing the cell. Six types of lysosomotropic amines have been prepared that all behave in the expected manner. They are cytotoxic to all lysosome-bearing cells but not red blood cells, which lack lysosomes. Their mode of action, the effect of alkyl chain length on activity, and the fact that their cytotoxic action appears only above a threshhold intracellular concentration support the belief that they behave as lysosomotropic detergents. Among the potential applications is cancer chemotherapy.


5-[(4-Methyl-1,2,3,4-tetrahydroquinoxalyl)methyl]-2'-deoxyuridine 5'-phosphate: an analogue of a proposed intermediate in thymidylate synthetase catalysis.

In a study of the sequence steps involved in the mechanism of thymidylate synthetase catalysis, 5-[(N-methyl-piperazinyl)methyl]- (5) and 5-[(4-methyl-1,2,3,4-tetrahydroquinoxalyl)methyl]-2'-deoxyuridine 5'-phosphate (6) were synthesized. Compound 6 has high affinity for the Lactobacillus casei enzyme (Ki = 0.75 microM, KI/Km - 0.23), which is 50 times stronger than that of the piperazinyl derivative 5. Compound 6, a possible multisubstrate inhibitor, is an analogue of a proposed intermediate in the reaction mechanism wherein the enzyme is eliminated from the covalent complex (enzyme--substrate--cofactor) prior to the redox reaction leading to the products 2'-deoxythymidine 5'-phosphate and 7,8-dihydrofolic acid.


5-Cyano-2'-deoxyuridine 5'-phosphate: a potent competitive inhibitor of thymidylate synthetase.

The 5'-phosphate (1) of the antiviral nucleoside 5-cyano-2'-deoxyuridine was synthesized and evaluated for inhibition of thymidylate synthetase purified from methotrexate-resistant Lactobacillus casei. Compound 1 was a potent competitive inhibitor with a K1 of 0.55 microns. Irreversible enzyme inhibition by this compound could not be detected.


Antifungal agents. 4. Chemical modification of antibiotics from Polyangium cellulosum var. fulvum. Ester and amide analogues of ambruticin.

A series of ester and amide analogues of ambruticin (1) was prepared. The analogues were tested against Histoplasma capsulatum, Microsporum fulvum, Candida albicans and Streptococcus pyogenes. Structure-activity relationships are described.


The natural history of violence.

In the past, human violence was associated with food shortage, but recently it has increased even in relatively well-fed societies. The reason appears from studies of monkeys under relaxed, spacious conditions and under crowding stress. Uncrowded monkeys have unaggressive leaders, rarely quarrel, and protect females and young. Crowded monkeys (even well-fed) have brutal bosses, often quarrel, and wound and kill each other, including females and young. Crowding has similar behaviour effects on other mammals, with physiological disturbances including greater susceptibility to infections. All this appears to be a regular response to overpopulation, reducing the population before it has depleted its natural resources. Human beings, like monkeys and other mammals, need ample space, and become more violent when crowded. Human history is marked by population cycles: population outgrows resources, the resulting violence, stress and disease mortality cuts down the population, leading to a relief period of social and cultural progress, till renewed population growth produces the next crisis. The modern population crisis is world-wide, and explains the increase of violence even in well-fed societies. The solution to the problem of violence is to substitute voluntary birth control for involuntary death control, and bring about relaxed conditions for a reduced world population.


Reversible inhibition by lanthanum of the hydrosmotic response to serosal hypertonicity in toad urinary bladder.

In the urinary bladder of amphibia, hypertonicity of the serosal bath (SH) evokes an increase in transepithelial water permeability, the characteristics of which resemble the response to antidiuretic hormone (ADH). The ionic dependency, in particular for Ca2+, appears very similar for SH- and ADH-induced water fluxes. In the present experiments La3+ was used as a probe to study the Ca2+-dependency of the hydrosmotic response to SH in isolated urinary bladder of the toad Bufo marinus. Addition of La3+ (5 mM) on the serosal side of the membrane produced a significant and reversible increase in basal transepithelial water flux. The hydrosmotic response elicited by adding 250 mM mannitol to the serosal Ringer's solution was inhibited by 30% in the absence of serosal Ca2+. Similarly, the hydrosmotic response to SH was inhibited by 37%, 30% and 40% when 5 mM La3+ was added to the serosal medium 30 min before, concommitantly with, or 60 min after induction of SH. The inhibition of transepithelial water flux observed in the absence of serosal Ca2+ or in the presence of serosal La3+ was reversible. The results support a critical role for Ca2+ in the modulation of transepithelial water permeability in the urinary bladder of amphibia. Ca2+ presumably exerts its effects at a post-cyclic AMP step.


Concentration-dependence of nonelectrolyte permeability of toad bladder.

A theoretical formulation was derived for the dependence of bulk solute permeability, P, defined as net flux divided by concentration gradient, delta c, across any membrane in which solute concentration is controlling for net flux, delta J. According to this formulation, delta J is stimulated by increments in trans concentration, c2, in the range c2/c1 equals 0.0--0.1. Net flux of urea across toad bladder down concentration gradients was shown to be stimulated threefold by small increments in trans urea concentration. The theory also predicts that, in the absence of concentration gradients, tracer permeability, P, defined as tracer flux divided by tracer concentration, will be independent of c provided that P equals P, but will diminish with increasing c if P/P less than 1.P/P was not significantly different from unity for urea, and both P and P were independent of c in the absence of concentration gradients. However, P/P was significantly less than unity (0.90 and 0.85) for thiourea and mannitol, respectively. In conformity with theory, P (and also P) of these two solutes, measured as c was increased by 3--4 orders of magnitude, diminished progressively. These effects are more consistent with this formulation than with transport via a saturable carrier.


Transient potassium fluxes in toad skin.

Experiments were carried out in the isolated short-circuited skin of the toad Bufo marinus ictericus. 42K influx and efflux experiments were carried out with skins bathed on both sides by NaCl-Ringer's solution. Those fluxes showed very similar kinetics of equilibration with time and the results could be fitted by equations of a model of two intraepithelial compartments and the bathing solutions. In the steady state K influx is 3.99 +/- 0.36 nmol cm-2 hr-1 (n = 7) and efflux 3.62 +/- 0.38 nmol cm-2 hr-1 (n = 7) and are not statistically different, indicating that no net K flux is present across the epithelium. Different kinds of perturbations affecting the rates of 42K discharge into the bathing solutions were studied. Immediately after addition of amiloride (10(-4) M) to the outer solution, a sharp decline is observed in the rate of 42K discharge into the bathing solution, JK21, which falls from 3.62 +/- 0.38 nmol cm-2 hr-1 to 2.02 +/- 0.04 nmol cm-2 hr-1 (n = 7) 2 min after addition of the drug, followed by a partial recuperation with time. A complete Na by K substitution in the outer bathing solution induces a prompt and marked decline in JK21 which is similar to that induced by amiloride. Increase in the outer bathing solution Na concentration from zero Na concentration induces a nonlinear increase in JK21 and a linear relationship was observed between JK21 and short-circuit current in the range of 0 to 115 mM external Na concentration. The decline in JK21 induced by amiloride or by lowering external Na concentration was interpreted as being caused by electrical hyperpolarization of the external barrier of the epithelium induced by these procedures. Depolarization of the epithelial barriers by inner Na by K substitution in the short-circuited state (when the potential barriers are equal) drastically interfere with the rate of 42K discharge from the epithelium into the bathing solutions. Thus, transient increases are observed both in the rate of 42K discharge to the outer and to the inner bathing solutions upon depolarization of the barriers. These results indicate that at least the most important component of transepithelial K unidirectional fluxes goes through a transcellular route with a negligible paracellular component. Addition of ouabain (10(-3) M) to the inner bathing solution induces a transient rise in the rate of 42K discharge to the outer bathing solution with a peak on the order of 200% of the stationary value previous to the action of the inhibitor, followed by a return to new stationary values not statistically different from those observed previously to the effect of ouabain. The behavior of JK21 upon the effect of ouabain, as suggested by comparison with predictions from computer simulation, strongly supports the notion of a rheogenic Na pump in the inner barrier of the epithelium against the notion of a nonrheogenic 1:1 Na--K pump.


Organochlorine compounds in adipose tissue of Greenlanders and southern Danes.

Abdominal fat tissue samples from the general population of Greenland and from southern Denmark were analyzed for o,p'-DDE and p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], p,p,-DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane], o,p'-DDT and p,p'-DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], lindane (1,2,3,4,5,6-hexachlorocyclohexane), aldrin (1,2,3,4,10,10-hexachloro-1,4,4a,5,8,8a-hexahydro-endo-exo-1,4:5,8-dimethanonaphthalene), dieldrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-endo-exo-1,4:5,8-dimethanonaphthalene), heptachlor (1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-methanoindene), heptachlor epoxide, and polychlorinated biphenyls (PCBs). Fat tissue from Greenlanders contained significantly higher amounts of p,p'-DDE (p less than or equal to 0.05), p,p'-DDT (p less than or equal to 0.01), and total DDT (SIGMA DDT, the sum of DDT and its metabolites) (p less than or equal to 0.01) than southern Danes. Lindane, aldrin-like residue, dieldrin heptachlor-like residue, heptachlor epoxide, and PCBs were present in adipose tissue of both groups and there were no significant differences between the groups. The p,p'-DDE level in Greenland was lower than that in the United States, eastern Europe, and India. Among Greenlanders of different ages the highest sigma DDT was found in the age group of 22-45 yr; the content of PCBs increased with age. Among southern Danes the highest sigma DDT was found in a higher age group than in Greenlanders. Among Greenlanders the content of aldrin-like residue decreased with age and that of dieldrin increased with age. A significant correlation was found (on the basis of wet weight) between p,p'-DDE and PCB content in southern Danes (p less than or equal to 0.02). The correlation between sigma DDT and PCB content was also significant in this population (p less than or equal to 0.01). These two relationships were not significantly correlated for the Greenlanders. The DDE/PCB and sigma DDT/PCB ratios were higher in Greenlanders than in southern Danes. These ratios are age-dependent and are highest in the age group 22-45 yr among the Greenlanders. A low DDE/PCB ratio and a low sigma DDT/PCB ratio have been proposed as markers for industrialization. In Greenlanders p,p'-DDE represented about 70% of sigma DDT. For southern Danes this level was about 90%. The data obtained are presented and discussed on the basis of both lipid and wet weight levels.


Effects of sevin on development of experimental estuarine communities.

The composition of animal communities developing from planktonic larvae in aquariums. A marked increase in the abundance of the annelid Polydora ligni in aquariums containing sand and flowing estuarine water was altered in the presence of the carbamate insecticide Sevin (carbaryl). Treatments were control and concentrations of Sevin that averaged 1.1, 11.1, and 103 micrograms/l; each treatment was replicated 8 times. Animals that colonized aquarium sand were collected in a 1-mm mesh sieve after 10 wk of exposure. Mollusks' arthropods, annelids, and nemerteans were the numerically dominant phyla. The average number of species per aquarium was significantly less (alpha = 0.05) in aquariums containing 11.1 or 103 micrograms/l than in those containing 1.1 micrograms/l or in control aquariums. The abundant clam Ensis minor grew significantly less in length at the higher concentrations of Sevin. The amphipod Corophium acherusicum was particularly affected; significantly fewer were found at all concentrations than in the control aquariums containing 103 micrograms/l corresponded to a marked decrease in the number of other annelids and to a significant absence of nemerteans.


Effects of hypercaloric glucose infusion on lipid metabolism in injury and sepsis.

Lipolysis was studied by measuring glycerol turnover (GTO) in injured and infected patients. GTO was elevated two to three times the normal values in five injured and four infected patients during D5W infusion. No correlation was found between GTO and plasma glycerol concentration in the two patient groups. GTO showed similar levels when measured during TPN in five injured and three infected patients. During TPN, plasma FFA levels remained unchanged in injured but decreased by 48% in septic patients. B-OH butyrate concentrations were high during D5W and dropped in both groups during TPN. Norepinephrine urinary output was high in both groups during D5W and TPN. 1) GTO was elevated two to three times the normal range in injury and infection; plasma glycerol concentration was not related to GTO. 2) In face of high catecholamine output, the insulin response to TPN did not inhibit TG breakdown but did decrease plasma ketone body concentrations.


Prevention of diabetic ketoacidosis.

Absolute deficiency of insulin no longer is considered the principal cause of ketoacidosis. A combination of pathogenic mechanisms includes (1) relative insulin deficiency, (2) stress hormone excess, (3) fasting, and (4) dehydration. Prevention of any one or more of these mechanisms will reverse or lessen the rate of metabolic decompensation. Several important metabolic parameters must be monitored at frequent intervals to permit rational, preventive therapy. The flow sheet to be maintained by the patient should include body weight, temperature, respiratory rate, level of consciousness, degree of ketonuria, and degree of glycosuria. If the patient exhibits decreased mental status, more than 5% loss of body weight, or respirations more than 36/min, hospitalization is indicated.


Surveillance of antibiotics use in a community hospital.

An ongoing system of antibiotic surveillance was initiated in a community hospital. The system was based on the guideline audits of antimicrobial use published by the Veterans Administration Ad Hoc Interdisciplinary Advisory Committee on Antimicrobial Drug Usage. The surveillance is accepted well by the medical staff. It has proved to be cost-effective and educational. A changing pattern of antimicrobial drug use has been recognized that has resulted in decreased antimicrobial drug costs.


[Effect of combination of hetacillin, cephapirin and amikacin (author's transl)].

With the investigations of the effect of combination of hetacillin, cephapirin and amikacin, following experimental results were obtained; 1. Effect of combination of amikacin, cephapirin and hetacillin was differed depending upon the genus and species of bacteria. However, in general, in the cases showing effective results there was a relation in the concentration of these antibiotics. With strains of Escherichia coli amikacin and cephapirin was cooperative, but not with other combinations and strains of Proteus showed similar tendencies to those strains. In the strains of Pseudomonas, no effect was observed with these antibiotics. However, significant cooperative effect was shown in strains of Klebsiella pneumoniae. In penicillin-resistant strains of Staphylococci cooperative effect was represented only a combination of amikacin and hetacillin. 2. Amikacin was resistant against penicillinase isolated from penicillin-resistant strain of Staphylococcus and cephalosporinase extracted from cephalosporin-resistant strain of Escherichia coli. 3. When a strain of K. pneumoniae, showing cooperative effect with amikacin and cephapirin, was examined by electronmicroscopy, enlargement of cells and destruction of the cell walls were observed.


Protection against hemorrhagic pneumonia of mink by Pseudomonas aeruginosa multicomponent vaccine.

An attempt to prevent epidemics of hemorrhagic pneumonia in mink due to Pseudomonas aeruginosa was made in the course of epidemics with injection of the multicomponent vaccine consisting of common protective antigen (OEP) of P. aeruginosa mixed with toxoids of protease and elastase of the bacillus. Enzootics of hemorrhagic pneumonia, due to P. aeruginosa serotype 8, broke out from August to October 1977 in a total of 13 sheds of 3 farms (A, B and C) which were located in the northeast area of Hokkaido. These farms were raising 7,452, 2,553 and 10,639 mink respectively. The mortality rate of the mink on farms A, B and C were 11.8%, 13.0% and 1.0% respectively. The vaccination was performed on the 3 farms 5, 8 and 21 days after the onset of the disease. Inoculation of each mink with 200 micrograms or 100 micrograms of each of the three components of the multicomponent vaccine was effective in most of the male and female groups of mink. The period required for revealing the effect of the vaccination was very short, in some cases only a few days. Administration of the vaccine 21 days after the onset of the enzootic was also effective.


Circadian rhythms of locomotor activity in the squirrel monkey, Saimiri sciureus, under conditions of self-controlled light-dark cycles.

Locomotor activity was recorded from three squirrel monkeys, Saimiri sciureus, housed singly in cages inside a sound-proof chamber. Each animal was exposed twice to each of three conditions; continuous dim illumination (dim LL), continuous bright illumination (bright LL), and conditions in which the animal could turn on bright light by itself (self-controlled light-dark cycle: LDs). The mean circadian period, tau, the activity time, alpha, and the amount of activity, A, were computed for each single condition. It was found that, in LL, tau, alpha and A were positively correlated with the intensity of illumination. In LDs, tau was longer and A larger than in either dim or bright LL. The lengthening of tau in squirrel monkeys by a self-controlled light-dark cycle is compared with similar findings in birds and man, and is discussed in view of the observation that the tau-characteristics of diurnal mammals deviate from those known from other diurnal species of vertebrates.


The Frenchman's fibular fracture (Maisonneuve fracture).

Two patients with injuries to the ankle sustained by rotational trauma complained only of pain in the ankle. Careful examination revealed tenderness over the proximal fibula. Subsequent radiographic studies revealed high helical fracture of the fibula, as originally described by Maisonneuve. The Maisonneuve fracture is produced by diastasis - a separation of bones resulting from rupture of ligaments around the ankle. According to classification of fibula injuries by mechanism of injury, the Maisonneuve fracture is due to external rotation of the foot relative to the tibia but it is not clear whether the foot is in pronation or supination or moves during injury.


[Results of prospective studies of patients with unstable angina pectoris treated by conservative methods].

The results of perspective follow-up (in the duration of 19 months) of 92 patients with unstable angina pectoris treated by nonoperative methods are discussed. During hospital stay all patients received propranolol (inderal) in a mean dose of 240mg daily and preparations of depo-nitroglycerin. In most patients the treatment was conductive to marked clinical improvement in their condition. In a follow-up period of one month myocardial infarction developed in 6.7% of patients, mortality was 3.4%. It is concluded that the syndrome of unstable angina pectoris, although associated with increased risk of myocardial infarction developing, is not an "incurable" condition. The use of nitroglycerin and adrenergic beta-blocking agents provides for the stabilization of the condition of most patients.


Nonnutritive sucking during tube feedings: effect on clinical course in premature infants.

Fifty-nine infants, 28--34 weeks' gestation, were assigned to treatment and control groups. Treatment infants were offered a pacifier during and following every tube feeding; control infants received routine care. The treatment began when an infant could tolerate room air and 10 cc of full-strength formula by tube; it ended when the infant was totally bottle fed. Treated infants showed readiness for bottle feeding 3.4 days earlier, i.e., with 27 fewer tube feedings each. Performance during the first bottle feeding was assessed with a feeding scale and was statistically similar for both groups. From study entry to first bottle feeding the treated infants gained 2.6 gm/day more and were discharged 4 days sooner. Complications differed between the two groups.


Early endothelial changes in experimental primate atherosclerosis.

Aortic tissues of cholesterol-fed African green monkeys were studied by light and electron microscopy. The sampled areas were either grossly normal, or showed minute grayish white translucent or yellowish white intimal elevations. Samples of topographically corresponding areas from animals on normal diet served as controls. By light microscopy, the intimal elevations were either pure fatty dots or a combination of fatty dots and focal intimal edema. The most conspicuous ultrastructural findings in the experimental animals were a marked increase in the number of Weibel-Palade bodies, and figures suggestive of release of their content into the vascular lumen. Invaginations or pseudochannels of varying depth as well as intracytoplasmic lipid inclusions were also observed in the experimental series. These findings suggest that Weibel-Palade bodies may play a role in the initial stages of atherosclerotic lesions, and that transendothelial transport may take place via transendothelial channels.


Analysis of ribosomal proteins from adult Drosophila melanogaster in relation to age.

Analysis of high salt washed ribosomal proteins by two-dimensional polyacrylamide electrophoresis revealed no detectable qualitative differences in ribosomal proteins from young (4-day) and old (30-day) male flies.


Alteration of the Q family of transfer RNAs in adult Drosophila melanogaster as a function of age, nutrition, and genotype.

Four tRNAs are known to contain Q, a hypermodified form of guanosine, in one of their isoacceptor forms; these are tRNATyr, tRNAHis, tRNAAsp, and tRNAAsn. The first three have been examined in Drosophila melanogaster at different ages in four genotypes. As the adult flies age, the ratio of the Q/non-Q isoacceptors increases, and the rate of increase is more rapid for Samarkand than for Oregon-R (two wild-type strains). Similarly, two other strains that carry the mutations su(s)2 v; bw and v; bw also differ in the rate of isoacceptor alteration. Diet has a marked effect on the ratio of Q/non-Q isoacceptors for each tRNA. tRNALeu does not change with age or diet and is believed not to contain Q in any of its isoacceptors. The possible role of Q in altering the rate of protein synthesis was examined in a cell-free, tRNA-dependent, mRNA-dependent system. No essential effect on the rate or extent of protein synthesis was detected upon comparison of Q-enriched or Q-deficient tRNA. The ratio of Q/non-Q isoacceptors for these tRNAs is clearly controlled by age-related and diet-related mechanisms that can modulate the amount of Q in the tRNA. The relationship of these studies to Strehler's hypothesis of age-related control of protein synthesis is discussed.


Racial differences in medical care expenditures.

Out of pocket medical expenditures made by families for physician services, dental visits, medications, hospitalizations and insurance premiums are examined in a southern rural community using household survey interview data. White families paid an average out of pocket amount for total medical services of $709 as compared with $383 for black families over a 12-month period, 1974-75. Correlates of expenditure differences between blacks and whites are explored with respect to family characteristics (race, education of household head, family income, family size and family composition), illness levels (number of family members with perceived fair or poor health status and number of family members reporting chronic conditions), and use of services (number of doctor visits and type of usual source of care). We find that whites consistently report greater expenditures than blacks, regardless of the variables controlled for. We consider that expenditure differences are in part due to a mix of three factors: variations in the cost of doctor visits to whites and blacks; a lower level of use of services by blacks; and the differential availability and use of third party payors.


[Pathogenesis of alcoholic liver injury (author's transl)].

The effects of ethanol on hepatic cellular metabolism and structure depend mainly on the dose and duration of intake. Following the ingestion of a substantial amount of ethanol, its presence alters a number of hepatic functions in part because of the change in the hepatic redox state (NADH/NAD ratio), resulting for instance in reduction of lipid oxidation. Furthermore, chronic ethanol consumption, at least in its early stages, produces adaptive metabolic changes in the endoplasmic reticulum which result not only in increased metabolism of drugs and accelerated lipoprotein production but also in activation of hepatotoxic compounds. Even more extended periods of ethanol intake result in damage to cell organelles in what can be considered a third stage of the alcohol effect namely that of injury. The injury involves primarily mitochondria, possibly as a consequence of effects of acetaldehyde, the first product of ethanol metabolism. Metabolites of ethanol also alter microtubular function. A defect in protein secretion may be the basis for protein retention and "ballooning" of the hepatocyte. Prolongation of ethanol induced injury eventually culminates in hepatic lesions such as alcoholic hepatitis and cirrhosis. Ethanol can be incriminated as a direct etiologic agent of the liver injury, since liver cirrhosis has been reproduced experimentally in baboons fed alcohol, despite an adequate diet.


The use of a small programmable calculator in intravenous feeding.

This paper describes a method using a programmable calculator to determine intravenous nutritional requirements of severely ill patients. A description of the method and calculations used is given. The advantages of this system are shown to lie in its easy availability to all hospital departments.


Prenatal protein depletion and delta 9, delta 6 and delta 5 desaturases in the rat.

Pregnant rats were kept throughout gestation on a control diet (i.e., 25% protein), on a low protein diet (i.e., 5% protein) or on a fat-free diet. At 20--21 days of gestation, the rate of 9-, 6-, and 5-desaturation was measured, using microsomes from maternal and fetal livers and placenta microsomes. The effect of protein malnutrition was more evident upon delta 6-desaturase activity from maternal liver, while a less severe reduction in the activities of delta 9- and delta 5-desaturases was observed. No measurable activities of delta 5- and delta 6-desaturases were observed in fetal liver and placenta, while a low activity of delta 9-desaturase was detected in both tissues from the three groups under study. We concluded that delta 6-desaturation is greatly affected by maternal protein deprivation, and this fact could affect the normal supply of polyunsaturated fatty acids for the normal fetus growth and tissue development.


Partial purification of guinea pig MIF by affinity column chromatography using macrophages.

First we have confirmed the previous observation that the macrophage migration inhibitory factor (MIF) was adsorbed on normal peritoneal macrophages when they were incubated at 4 C for 60 min. It was found that macrophages fixed with 2% glutaraldehyde gave more reproducible results than viable cells in terms of "adsorption" of guinea pig MIF. The adsorption was achieved more completely at 37 C than at 4 C, indicating that this reaction is a temperature-dependent phenomenon. Using these glutaraldehyde-fixed macrophages, a kind of cell-affinity column was successfully developed. The guinea pig MIF preparation lost its activity when it was passed through this affinity column, and MIF adsorbed on the column was recovered by elution with 0.1 M (L)-fucose of 0.1 M (D)-glucose. Such MIF active eluate was found to be at least 30--40 fold more pure than the original MIF preparation which had been previously fractionated according to its molecular weight. Therefore, this type of macrophage-affinity column may be useful for the purification of MIF.


Immaturity of the biliary excretory system predisposes neonates to intrahepatic cholestasis.

Intrahepatic cholestasis associated with both gram-negative bacterial infections and total parenteral nutrition (TPN) is observed more frequently in neonates than in older children or adults. Factors involved in the pathogenesis of this syndrome are uncertain. The cholestatic effects of gram-negative bacterial infections appear to result from the inhibitory effects of endotoxin on bile flow. Since the adverse effects of both endotoxin and TPN on bile flow involve primarily the bile acid-independent portion, the immaturity of the neonatal hepatic excretory system which an inadequate bile acid-dependent fraction of bile would explain the increased susceptibility of the neonate to endotoxin- and, perhaps, to TPN-induced cholestasis.


A hypothesis for the interaction of heme and arachidonic acid in the synthesis of prostaglandins.

A model is proposed for the interaction of arachidonic acid with the heme associated with the cyclo-oxygenase enzyme which synthesizes prostaglandin endoperoxides. According to this concept, arachidonic acid attaches with its carboxylic acid residue to one ligand of the Fe++ in heme, then curls around the outside of the protoporphyrin to react with a molecule of oxygen associated with the ligand of the Fe++ on the other side of the protoporphyrin with addition of O2 at the C11 carbon, ring closure across C8-12, formation of the C9-11 endoperoxide and then addition of a second oxygen at C15 with an allylic shift of the double bond. This concept may resolve several experimental findings relating to the mechanism of prostaglandin synthesis and can account for much of the stereospecificity in the conversion of arachidonic acid to prostaglandin G2.


Screening of newborn infants for hypothyroidism. Two years' experience in South Autralia.

Over a period of two years, 40,000 newborn infants in South Australia have been screened for congenital hypothyroidism by the measurement of thyroxine and, on selected samples, of thyroid stimulating hormone. Samples were those obtained for an established newborn screening programme in the State. Eight infants with hypothyroidism were detected; in seven, this was due to congenital agenesis of the thyroid gland and one infant had residual thyroid tissue. A further three sick infants had abnormalities of thyroid function; in two, this was transient and reverted to normal after several weeks and the third infant died. Three infants had thyroxine-binding globulin deficiency.


Pseudomonas aeruginosa keratitis treated with ticarcillin and tobramycin.

A corneal ulcer, infected with Pseudomonas aeruginosa and complicated by conjunctivitis and endophthalmitis, was treated successfully with systemic administration of ticarcillin and topical application of tobramycin. It is unlikely that carbenicillin, to which the organism was much less sensitive, would have attained sufficient tissue levels to control the infection.


The diagnosis of gonorrhoea in women.

Gonorrhoea was diagnosed in 258 of 1500 women. The diagnosis was made from urethral plus cervical cultures in only 184 cases (71.3%). The percentage of positive diagnoses rose to 96.5% when cervical smear microscopy was also performed. This highlights the need to carry out all three investigations. Concurrent Trichomonas infection was present in 14% of cases.


[Pseudodiverticulosis of the esophagus (author's transl)].

The autopsy of a 59 years old male incidently revealed a pseudodiverticulosis of the esophagus. Histologic examination demonstrated typical cystic ectasies of all glandular ducts in the esophagus; they appeared on radiologic examination and are visible at endoscopy as little yellowish cystic lesions. The disease usually is of chronic nature and comprises disturbance of motility and passage. Chronic alcoholism, like in our case, often constitutes a concomitant disease. The etiology of this disorder is unknown. Certain clinical aspects should be considered.


Presumptive identification of enterococci from other D streptococci by a rapid sodium chloride tolerance test.

Ability of enterococci to cause severe disease in humans and their relative resistance to chemotherapeutic agents necessitate their differentiation from other group D streptococci. We developed and evaluated a medium that differentiates enterococci from other group D streptococci within 4 to 24 hours. The 410 clinical isolates used in this study consisted of 328 strains of enterococci and 82 strains of other group D streptococci. The method showed 100 percent sensitivity and specificity with the conventional sodium chloride test. It is simple, reliable, and rapid.


Linear accelerator calibration monitor with a memory.

A calibration monitor has been designed for measuring the constancy of linear accelerator or cobalt unit output between full calibrations. This monitor is battery operated, light-weight and slides into the shadow tray attachment on a linear accelerator or cobalt unit for easy setup. It provides a digital readout of the dose delivered, and a consistency check can be made in less than two minutes. The precision of the monitor, determined by cobalt-60 irradiations over a 2 1/2 period, is +/- 0.6% (standard deviation). The monitor also retains the dose reading in a CMOS digital counter indefinitely, hence it can be used in the same fashion as mailed thermoluminescent dosimeters (TLD) for calibration checks at remote facilities without the complicated readout procedures associated with TLD. The monitor can be mailed to a remote facility, positioned without ambiguity, and irradiated; and the reading can be verified on return to the originating center simply by pressing a switch. The monitor can easily be set up to carry out a "blind" check in which the reading obtained is not known to the remote facility.


Glucocorticoids and hepatic glycogen metabolism.

The steady accumulation of glycogen in fetal rat liver during the last fifth of gestation is elicited by a transient rise in the level of circulating corticosterone. One effect of glucocorticoids is to induce glycogen synthase. The actual deposition of glycogen, however, depends on the appearance of a small amount of glycogen synthase in the active, dephosphorylated form. Induction of glycogen synthase phosphatase by glucocorticoids may explain the latter crucial process. Insulin enhances further the rate of glycogen deposition. The effect of insulin requires a previous exposure of the fetal liver to glucocorticoids. It is exerted on the enzyme interconversion system and appears not to involve new protein synthesis. Administration of glucocorticoids to adult fed or fasted animals causes within 3 h an intensive deposition of glycogen in the liver. This phenomenon is ultimately explained by both an activation of glycogen synthase and an inactivation of glycogen phosphorylase. The latter process may be due to an enhanced activity of phosphorylase phosphatase, or possibly of phosphorylase kinase phosphatase. The activation of glycogen synthase is explained by an enhanced activity of glycogen synthase phosphatase. The latter enzyme is normally profoundly inhibited by phosphorylase a; glucocorticoids cause the appearance in the liver of a protein factor that decreases and eventually cancels this inhibitory effect of phosphorylase a. It remains to be established whether or not some part of the glucocorticoid effect on adult liver is mediated by insulin.


[Psychoses and borderline cases in puberty and adolescence and their importance in criminal law (author's transl)].

Juvenile psychoses are on the whole rare, at any rate rarer than psychoses in adults. The former commonly used conception of the disease, hebephrenia, as a pubertal form of schizophrenia has largely lost its significance. The cardinal symptoms are delusions and disordered mental processes in addition to anxiety and states of excitement. The particular importance of this disease lies in the individual experience of this disturbance of the reference environment which is an existential threat to a newly formed personality and its relation to the environment. The difficulty in classifying it among the psychoses on the one hand and as a neurosis on the other has produced a term "borderline" for it, characterized by an infantile incompatibility with positive and negative tendencies in himself and in reference persons and through the lack of a stable reality of reference.


[Adolescent crises in puberty. Diagnosis and therapy (author's transl)].

Psychological disorders which become manifest as adolescent crises must be seen as complex phenomena and treated thoroughly: besides the genetic, biographic and psychosocial background of the youthful individual the cultural and economic aspects play an important role. Nevertheless we must admit that associated causal explanations, e.g. for accelerated or late development are lacking. Focal points for the subsequent symptom complexes of sexual behavior in puberty are: psychosexual prematurity or retardation, masturbation, homosexual relations, pubertal asceticism and premature and frequently changing sexual relations.


[Cimetidine in the preoperative treatment of acute bleeding gastroduodenal lesions (author's transl)].

Whereas prospective studies seem to substantiate the efficacy of cimetidine treatment in the prophylaxis of acute gastrointestinal hemorrhage, communications on the therapeutic effect of cimetidine at the bleeding stage are contradictory. Our own experience is based on the treatment of 36 patients with acute hemorrhage of the upper gastrointestinal tract. Cimetidine was applied as a continuous drip, the objective being early operation when bleeding stopped, especially in peptic lesions. A primary cessation of bleeding was attained in all patients during the first 4 hours.


[Bioavailability of iron in oral iron preparations. Principles of duration and dosage (author's transl)].

Using 59Fe labeled iron preparations, both the exactly and quantitatively determined absorbability by whole body retention measurement of the absorbed 59Fe and the calculated relative bioavailability from the postabsorption rise in serum iron concentration have coincidently shown that only about half as much Fe (II) is absorbed from oral iron preparations with delayed liberation of iron in the small intestine than from an Fe (II) preparation liberating Fe (II) more rapidly in the stomach. From preparations with trivalent iron only 1/7 to 1/20 of the amount of iron is absorbed which can be absorbed from an Fe (II) preparation with a more rapid rate of Fe liberation. The optimal oral iron therapy is therefore with aqueous solutions of Fe (II) or Fe (II) preparations which disintegrate immediately in the stomach.


[Treatment of diabetes without biguanides. Observation on the course after changing treatment (author's transl)].

In 56 patients with maturity onset diabetes receiving combined therapy with different oral hypoglycemic drugs, biguanide treatment was stopped while sulphonylurea compounds were continued without major changes. In four patients insulin therapy had to be initiated rapidly. In 14 other patients follow-up observations could not be performed for various reasons. The reamining 38 patients were divided into four groups according to their treatment. On the average, chemical control could not be maintained in any group after discontinuation of biguanide therapy. Blood glucose concentrations and glycosuria increased. Later, in 6 of 38 patients secondary failure of sulphonylurea treatment became apparent.


[General medicine--a specialty in its own right (author's transl)].

The daily tasks of a general practitioner as they are laid down in the professional regulations and substantiated in the subsequent performance justifies the recognition of general practice as a special field of medicine in its own right which should be represented in teaching and research. In contrast to some neighboring countries, here in the Federal Republic of Germany the development is still in its early stages, which in the interest of the matter, especially of the patients and their families, should be overcome as quickly as possible.


[Treatment of primary chronic polyarthritis with ranoroc (author's transl)].

In the framework of a clinical study the butazone derivative Ranoroc was tested for efficacy and tolerance in 50 patients with primary chronic polyarthritis. The success rates both in previously treated and untreated patients were approximately equal, i. e. 92%. In the previously treated group, a superior effect of Ranoroc as compared with the earlier treatment was stated by the patients in 57% and by the physician in about 36% of the cases. The tolerance was very good. Nausea and heartburn occurred in 3 cases only and were controlled by reducing the dosage. Discontinuation of the trial was required in two cases on account of skin allergies. The continuously monitored laboratory parameters gave no evidence whatsoever of a negative influence, so that even a longterm treatment with Ranoroc seems possible.


[Preventive and therapeutic application possibilities of newer antibiotics (author's transl)].

Today, however aminoglycosides are nearly indispensable owing to their broad antibacterial spectrum and genuine bactericidal effect as well as the possible synergic effect with beta-lactam preparations. The new cephalosporins are distinguished by a high beta-lactam stability and are active against the majority of pathogens causing nosocomial infections. An exceptional position is held by cefotaxim with its generally outstanding antibacterial potency, and by cefoxitin with its activity against Bacteroides fragilis. The ureidopenicillin azlocillin is superior to the Pseudomonas penicillins so far used. It acts against enterococci and H. influenzae as reliably as does mezlocillin.


[Prophylactic use of antibiotics (author's transl)].

The correlation between extensive aminoglycoside usage and the resistance of P. aeruginosa and Enterobacteriaceae (up to 40%) is a particularly striking aspect in hospitals. Favourable conditions for an effective prophylaxis are the limitation to one pathogen, a defined location and recent contamination. In so-called "clean" operations, prophylaxis is reasonably justified in exceptional cases only. Likewise, no benefit is to be expected from chemoprophylaxis in most of the so-called "clean-contaminated" surgical procedures. In septic surgery, antibiotic prophylaxis is indicated even if effectiveness is limited. Indiscriminate routine use, longterm treatment and local application of antibiotics to intensely contaminated areas is definitely not to be recommended.


[Nuclear power plant disaster. Medical assistance to the population (author's transl)].

The possibility of a nuclear power plant disaster is small but not excluded: in its event, assistance to the affected population mainly depends on local practitioners. Already existing diseases have to be diagnosed and treated; moreover, these physicians are responsible for the early detection of those individuals exposed to radiation doses high enough to induce acute illness. Here we present the pathogenesis, clinical development and possible diagnostic and therapeutical problems related to acute radiation-induced diseases. The differentiation of persons according to therapy need and prognosis is done on the sole base of the clinical evidence and the peripheral blood count.


[Legionnaires' disease in Munich. Case report and outline of the clinical picture (author's transl)].

Account is given of a patient with legionnaires' disease to highlight the increasing significance of this affection. The typical symptoms are described. Under doxycyclin at high dosage (200 mg/day) the patient became afebrile within 36 hours with concurrent improvement of his general condition. Distinct regression of the pulmonary infiltrate was seen within five days.


[Sympathalgia of the cervicobrachial region (author's transl)].

Pain syndromes in the cervicobrachial region may be an expression of irritation of the periarterial autonomic nervous system. They show a vasal, arterial topography (here of the subclavian artery). If the cervical sympathetic chain is involved in the irritation, the area supplied by the carotid artery, i.e. the homolateral half of the head is also affected. Characteristics of these disturbances are their abnormal topography, which cannot be classified either as a radicular nor a segmental pattern. In this region the perception of pain is delayed. The quality of pain is protopathic (dull, intense, burning). In the sympathalgia region there is lowering of the pain threshold (dysesthesia), vasomotor disturbance (dyskinesia) local homeostatic disorders (dyscrasia), in certain circumstances trophic disturbances (dystrophy) which are usually accompanied by marked depression (dysthymia).


[Genesis and treatment of Achilles tendon rupture (author's transl)].

Recent experimental studies on the Achilles tendon show that a rupture of the tendon can be caused by trauma. This statement is supported by the results of special examinations on intraoperatively excised tendon tissue. In the treatment of the rupture, the choice of surgical technique depends on the age of the rupture at the time of surgery. Ruptures less than 5 days old are sutured end to end with absorbable sutures whereas older ruptures frequently require a tendinoplasty. Finally we are developing an etiopathological interpretation of Achilles injury. From this it may be concluded that this was perhaps the first traumatic rupture of Achilles tendon to be described in the literature.


[Total hip prosthesis and sport (author's transl)].

The artificial replacement of the hip joint has become a routine operation the assessment of load resistance of the total hip prothesis (THP), on the other hand, is very variable. If at all possible, a THP should only be implanted in elderly people usually with the object of obtaining painless and improved walking ability. Occasionally, however, the question of the possibility of sports activities arises. But for this there are no practical pointers for better orientation. Therefore 120 operated patients under the age of 60 were questioned in detail on their sports activities and followed up. Then an attempt was made to classify the types of sport. Swimming, cycling, gymnastics, walking and rowing seemed suitable.


[The effect of various suture materials on wound healing. An experimental study in animals (author's transl)].

The reactions of connective tissue and fibers to silk, catgut, chromic catgut and polyglucolic acid fibers buried in the subcutis and to which a solution of vaccinia (WHO Elstree strain) or a control solution was added, were tested in 7 rabbits. Of the fibers tested, the histological picture on the 9th postoperative day showed that polygluconic acid fibers were by far the best, catgut fibers were particularly poor.


[Aplasia of the gallbladder (author's transl)].

In the clinical observation of a female patient with typical gallstone symptoms and corresponding diagnostic findings when gallstones and gallbladder were absent, further diagnostic and therapeutic procedures in gallbladder aplasia, a very rare anomaly of biliary tract anatomy, could be facilitated with the aid of comparative echography and computer tomography. Diagnostic and therapeutic failure appear to be avoidable by this means.


[Victimology of sexual crime. Examination of victims and the consequences for behavior, prophylaxis and therapy (author's transl)].

Medico-legal and criminological examinations of 93 sexual crimes are reported. This figure comprises all the crimes which have become known to the police during a certain period in one region. It is suggested that the medical examination by confined to specific wards of the gynecological hospital so that psychological care can be provided and the customary criminological investigation methods be changed. For preventive reasons, a general expertise of the offenders and credibility examinations of victims and offenders seem to be called for in the absence of satisfactory evidence. Physical resistance on the part of the victim in the present cases led to a significant increase in the injury and death rate. How far traditional social views toward women favor sexual crime is discussed.


[Peptic ulcer disease and primary hyperparathyroidism (author's transl)].

The causal relationship of primary hyperparathyroidism and ulcer disease is reviewed. In contrast to earlier ideas careful clinical and clinico-chemical investigations have shown that in patients with manifest primary hyperparathyroidism neither is the incidence of ulcer disease raised nor are deviations from the normal behavior of acid secretion or the serum gastrin level to be observed in comparison with the average population.


[The course of functional psychoses (author's transl)].

Functional psychoses correspond to a universal reduction of mental and intellectual function which, fundamentally reversible and unspecific, appear as sequelae of disturbances of cerebral function. They are the most common psychoses in medical practice and in hospitals. With the Syndrome Short Test and Functional Psychosis Scale B we now have a mutually equilibrated test system for the measurement of the whole range of severity of functional psychoses. With these two psychopathometric methods a relatively differentiated investigation of cross section and course can be performed, for example in arriving at a diagnosis, checking medical measures, monitoring the effect of drugs and in the prognosis of a disease.


[The effect of premedication with thalamonal on the plasma catecholamine levels (author's transl)].

The sympathetic suppressant properties of Thalamonal as a premedication is reported in both normotensive and hypertensive patients. The investigations were carried out in 27 patients altogether, of whom 7 were previously treated hypertensives. The plasma catecholamines noradrenaline and adrenaline, the blood pressure and heart rate were monitored before and after premedication.


[The mental patient as motorist. When is unfitness to drive involved? (author's transl)].

The bulk of road traffic accidents are not caused by ill drivers and even not at all by mentally ill drivers. So far as diseases are involved in the assessment of suitability to drive, the Joint Advisory Board for Medical Science relating to Traffic Safety and the Federal Minister for Youth, Family and Health have worked out standards for this. Examples were given and the principles were presented according to which expert opinions by doctors and specialists should be made. Otherwise difficulties arise in road traffic from the psychiatric point of view through the nonconformist behavior of the normal citizen who apparently finds it difficult to realize the principles of self-responsibility.


[Psychiatric diseases and driving fitness (author's transl)].

Mental factors frequently play a decisive role in the conditional setup of many accidents. Analysis of the mental factors determining the cause of accidents show these to be by far often mental factors of a non-pathological nature, such as personality factors, disordered concentration and alertness in conflict situations, overstrain and fatigue, than factors conditioned by illness, e.g. as associated with depression or schizophrenia. Psychological alterations in subjects of advanced age constitute a border area of high significance in medical science concerned with traffic safety. In the consulting room, particular attention should be paid to the recognition of potential risk constellations in traffic precipitated by alcohol or drugs.


[Impairment of driving ability by infections of the gastrointestinal region (author's transl)].

Experience shows that infections in the region of the gastrointestinal tract are apparently not very common causes of traffic accidents. In particular, impairment by the disease itself including treatment with its effects and side effects must be considered. Also the patient's own assessment of his condition is extremely meaningful and must not be disregarded at the consultation. Furthermore the length and circumstances of the journey and consideration of the age of the patient and other disease conditions are important.


Cytology of aberrations induced by X-rays in oocytes of Drosophila melanogaster.

200 first-division configurations were analyzed for cytological aberrations induced by X-rays in late meiotic prophase in oocytes of Drosophila melanogaster. For the 3000 and 6000 r doses, 38 and 66%, respectively, were classified as abnormal. The aberrant divisions included displacement of the chromosomes suggesting their non-disjunction, loss of a whole chromosome, fragments and heterologous exchanges and unidentifiable aberrations. Non-disjunctional chromosomes were free of heterologous exchanges. The concept that a majority of X-ray-induced dominant lethals is due to chromosomal breakage is supported by the findings of the present study.


Sensitivity of Drosophila melanogaster to low concentrations of gaseous mutagens. II. Chronic exposures.

Sex-linked recessive lethal mutations were induced in Drosophila melanogaster males by gaseous 1,2-dibromoethane at concentrations ranging from 0.2 to 2 parts per million. Significant numbers of mutations could be induced at all these concentrations. Pronounced germ-cell sensitivity differences were observed. For low exposures, spermatids and spermatocytes were about 10--20 times more sensitive than spermatozoa. The dose-effect relation was linear below 60 ppm . h for the 3 cell types. At higher exposures, sterility prevented mutation detection in spermatocytes and in spermatogonia. The lowest effective exposure for spermatozoa was 18 ppm . h (0.25 ppm for 72 h). In spermatids, the lowest exposure tested, 2.3 ppm . h (0.2 ppm for 11 h) induced 4 times the spontaneous mutation rate. Therefore, using prolonged exposure periods one may be able to detect concentrations in the range of parts per billion. Thus, Drosophila appears suitable as a system for detecting very low concentrations of gaseous mutagens in industrial, agricultural and environmental atmospheres.


Selective primary health care: an interim strategy for disease control in developing countries.

Priorities among the infectious diseases affecting the three billion people in the less developed world have been based on prevalence, morbidity, mortality and feasibility of control. With these priorities in mind a program of selective primary health care is compared with other approaches and suggested as the most cost-effective form of medical intervention in the least developed countries. A flexible program delivered by either fixed or mobile units might include measles and diphtheria-pertussis-tetanus vaccination, treatment for febrile malaria and oral rehydration for diarrhea in children, and tetanus toxoid and encouragement of breast feeding in mothers. Other interventions might be added on the basis of regional needs and new developments. For major diseases for which control measures are inadequate, research is an inexpensive approach on the basis of cost per infected person per year.


Evaluation of medical practices. The case for technology assessment.

We believe that the systematic evaluation of medical practices, especially those that are risky or costly deserves more attention. Available methods are limited, and definitive assessments of innovative or controversial practices are infrequent. Nevertheless, some evaluations have successfully enhanced the use of effective practices and diminished the reliance on ineffective ones. Greater efforts at evaluation can improve the quality of patient care, avoid waste and promote the more rational use of health resources. The cost of assessing new practices should be viewed as an intrinsic part of the cost of medical care. Physicians and medical societies bear primary responsibility for recognizing the need for this evaluation, for enlisting other experts, participating in technology assessment and working to translate the results of evaluation into practice. The commitment of government agencies, insurance companies and teaching institutions is also essential to an effective program of evaluation.


Case studies on the use and accuracy of synthetic estimates: unemployment and housing applications.

A description is given of unemployment synthetic estimates for counties, based on the 1970 Census of Population. The distribution of the method error of these estimates is given, as well as the relative accuracy of these estimates. Implications for intercensal estimates based on regression models are considered. Vacancy rates from the 1970 Census of Housing are discussed. Estimates of 1970 estimates of dilapidated housing units with all plumbing facilities and their accuracy are analyzed.


Drug abuse applications: some regression explorations with national survey data.

Personal interview surveys in recent years have provided national estimates of use of marihuana, heroin, and other substances. Over a number of national surveys, consistent relationships have been observed between drug abuse and demographic variables such as age, education, and sex. Where one lives has also been found to be significantly related to level of drug abuse. This is observed in survey data in relationships between experience with drugs and geographic region of residence and community size and type. Regression and other multivariate analyses have been used to help understand the prevalence of drug abuse among various segments of the general population and have provided a means to explore relationships between drug use and a number of additional factors related to location of residence. Regression procedures have also been used in an exploratory way to provide drug abuse estimates for States.


Applications of synthetic estimates to alcoholism and problem drinking.

This paper focuses on the application of synthetic estimation techniques to issues involving estimation of the prevalence of alcoholism and problem drinking. Demands for information led to the first use of synthetic estimation in this area. However, the experience of bringing that first application to fruition led to new uses where previously no attempt would have been made to develop information. Three examples are discussed briefly: estimating the relative prevalence among the States; identifying health manpower shortage areas; and calculating the need for service in a community.


Synthetic estimates as an approach to needs assessment: issues and experience.

An overview of a study which applied the synthetic estimates technique to derive rates, numbers, types and characteristics of potential clientele for substance abuse related programs in the State and counties of Oregon is presented. A brief description is given of the methods utilized to obtain estimates as well as the means for examining their validity. Inasmuch as the objective of the study was to provide useful information to State and local program planners and administrators, the experience of utilizing the study's findings is presented. Several applications are highlighted to indicate the range of ways in which the study was utilized. The experience of applying the results in a program and policy context surfaced several issues concerning the requirements for validity and accuracy, specificity and, finally, the role of synthetic estimates in needs assessment. The experience suggests that the information derived by this technique will be most useful if integrated with a range of other types of information, both quantiative and subjective.


A composite estimator for small area statistics.

Samples designed to provide estimates for large geographic areas are sometimes used to provide estimates for small areas. In such cases the sample in a small area may be "unrepresentative" or of small size. Various estimators, including a composite estimator, which is weighed function of two component estimators, have been suggested for use in these situations. The choice of weights for the composite estimator is considered in this paper. It is shown that with appropriate weights the composite estimator has smaller mean square error than either component estimator and also that this estimator is remarkably robust against poor choices of weights. Data from the National Center for Health Statistics' Health Interview Survey and the Bureau of the Census' Public Use Tapes are used to illustrate results when direct and synthetic estimators are used as components of the composite estimator.


Small area estimation--synthetic and other procedures, 1968-1978.

Methods for obtaining small area estimates which have emerged over the past decade are reviewed with particular emphasis given to synthetic estimation, a procedure originally developed at the National Center for Health Statistics which has found wide acceptance because of its simplicity and intuitive appeal, and yet has provoked much controversy because of its lack of good demonstrable statistical properties and its equivocal results when subjected to empirical evaluation. The various methods of obtaining small area estimates are discussed in terms of their statistical properties, the feasibility of using them and the potential scope of their application. Finally, some recommendations are made concerning possible avenues of future research in small area estimation, and some tentative guidelines are given for choosing between alternative existing methods.


Prediction models in small area estimation.

Finite population estimation problems are formulated as prediction problems under superpopulation models. For linear regression models, a general theorem on optimal linear estimation is presented. The theorem is applied to simple cross-classification models to generate and analyze various statistics for estimating small area totals. These statistics include the synthetic and composite estimators, as well as some interesting alternatives.


A modified approach to small area estimation.

The ever-growing need for good estimates of the health, social, political, and economic parameters of local areas has served as the motivating force for new developments in methodology. Due to the constraints of sample size, design, and cost, accessible data from large areas for criterion variables of interest is often used jointly with local data on symptomatic variables. Furthermore, several procedures have derived local area estimators by combining symptomatic information and sample data into a multiple regression format. In those situations where assumptions are too strict or unrealistic, as when a nonlinear model is more appropriate, the merits of a more flexible approach are obvious. Our research focuses upon a further investigation of an alternative strategy for which the most limiting assumption is the availability of good symptomatic information. A more formal representation of the model is developed within the framework of a poststratification scheme. The methodology involves ratio estimation of the respective stratum means via indicator variables which serve the purpose of classification. To determine the accuracy of the proposed small area estimator and allow for comparisons of precision with respect to other strategies, we express the relationship between criterion and symptomatic variables by relevant continuous multivariate distributions. Specifically, comparisons are made with the results obtained using a regression estimator which is applicable to the same general setting. The theoretical framework considers multivariate stratification, where boundary determination is achieved by application of practical methods which use minimum variance stratification as a criterion.


Female transference and mate choice among Tana River red colobus.

Red colobus are one of a small number of primate species in which females have been reported to transfer between breeding groups more commonly than males. Several authors have hypothesised that in such species transference may serve to reduce the risk to females of producing offspring of lower fitness through inbreeding. The hypothesis offers no explanation of why females rather than males are responsible for outbreeding in these species, but remains plausible so long as male membership of breeding groups is relatively stable; for once members of one sex have evolved dispersal mechanisms reducing the risk of inbreeding, pressures on the other sex to do likewise will be lowered. Hence, if both sexes commonly migrate, the hypothesis is weakened. I describe here the membership dynamics of a group of Tana River red colobus, Colobus badius rufomitratus, which provide the first evidence of high rates of membership turnover by both sexes in primates, and speculate that the function of female transference in this case may be related to mate choice and the avoidance of infanticide.


Correlation between fragmented immunoglobulin genes and heavy chain deletion mutants.

It is generally accepted that the variable (V) and constant (C) regions of immunoglobulin (Ig) chains are under separate genetic control. The notion that the different domains and interdomain regions are also under the control of independent genetic units was initially based on the clearcut results obtained by studying the primary structure of deletion mutants and received definitive support from direct analysis of cloned heavy (H) and light (L) chain genes. Here we present additional studies carried out on two selected gamma 3 deletion mutants which indicate the genetic control of human H chains may be even more complex than previously believed.


Precipitating antibodies against pseudomonas aeruginosa in serum from dialysis patients.

Hemodialysate in our facility was found contaminated with Pseudomonas aeruginosa. By means of crossed immunoelectrophoresis, series of serum samples from 20 patients in regular dialysis treatment have been investigated for development of precipitating antibodies against P. aeruginosa during dialysis treatment. In 6 patients antibacterial antibodies occurred during the observation period but were, in all 6 occasions, in close relation to acute intercurrent bacterial infections and not related to the dialysis treatment. It is therefore concluded that P. aeruginosa antigens from the dialysate do not pass the dialysis membranes in quantities sufficient to evoke a humoral immune response.


Evidence that serotonin stimulates a prolactin-releasing factor in the rat.

Methanol extracts of rat plasma resulted in release of prolactin (PRL) from rat hemipituitaries in vitro with a linear log-dose relationship. This prolactin-releasing factor (PRF)-like activity was not altered in plasma from rats treated with bromocryptine or chlorpromazine despite significant suppression and stimulation of plasma PRL levels, respectively. Fluoxetine, a serotonin reuptake inhibitor, plus 5-hydroxytryptophan, the immediate precursor of serotonin, markedly stimulated both plasma PRL and plasma PRF-like activity. Neither fluoxetine, 5-hydroxytryptophan, nor the combination directly stimulated PRL release from rat pituitary tissue in vitro. We conclude that serotonergic stimulation augments PRL release via a PRF.


Deciphering deinstitutionalization: complexities in policy and program analysis.

Deinstitutionalization as a public policy promised to be a major departure from previous psychiatric practice. Decrying traditional "medical paradigms" and the custodial "warehousing" of mental patients, policy makers advanced a "bold new approach" for care in the community. Progressive humanitarian reform could go hand in hand with fiscal conservatism. Community Mental Health Centers were to be the heart of a new national effort. But the rhetoric of reform failed to coalesce the activities among competing federal and state interests and systems. Intended beneficiaries may have become unfortunate victims.


In defense of deinstitutionalization.

Political and economic decisions contributing to deinstitutionalization had widespread support from psychiatrists, social reformers, and civil libertarians. The fortuitous advent of Medicaid and SSI abetted movement out of institutions, but these federal programs impede efforts to reform remaining state hospitals--yet progress has been achieved.


[Current status and problems of tuberculosis. 10 years of experience in a general medicine department].

One hundred and seventeen cases of tuberculous disease who came to the Authors' observation in 10 years are described. Some cases are illustrated in details just to point out the complexity and the different guises of clinical presentation and to underscore the importance of an high index of suspicion for tuberculosis in patients who are admitted to a ward of internal medicine. In 71 patients with active, progressive tuberculous disease, the diagnosis was confirmed by bacteriological findings in 29 cases and by bioptical and hystological data in 5 cases; in the remaining 37 cases only clinical and radiological criteria were met but the diagnosis was confirmed by the improvement which was observed after antimycobacterial therapy. Many difficulties have been met in the differential diagnosis between pulmonary tuberculosis and bronchogenic carcinoma in those cases with anamnestic and radiological data of previous pulmonary tuberculosis. When the radiological site of lesions was in the posterior segments of the lung, tuberculosis was the most probable diagnosis, while bronchogenic carcinoma is most oftenly localized in the anterior segments; only in 5 cases of the Author's series the above mentioned criterion was not satisfied. In 46 cases with clinical signs of inactive tuberculous disease which had not been adequately treated with chemotherapy, isoniazid was given only to those patients with a high risk of reactivation (silicosis, diabetes, chronic alcholism, gastric resection, prolonged steroid therapy). Two cases of isoniazid hepatitis were observed among patients treated by the Authors.


[Effects of gravitational forces on the nervous system].

The human being, submitted to G+ of G-, shows some adaptation mechanisms which beyond a certain limit can become pathological alterations. In this connection, some aspects concerning intraocular pressure, electrolytes and enzymes have been studied.


[Burns in an aeronautic environment].

Following an examination of the aetiology of burns in aeronautic environments, the physiopathology, classification and general and local treatment of the burn case is discussed. Special mention is then made of aircraft as an extremely useful means of transport.


Fetal-maternal transfusion following early abortion.

Therapeutic abortion has been a major potential source of Rh isoimmunization. Popularization of early termination necessitates reconfirmation of established policies. This study involved 75 patients, selected at random, in whom pre- and post-abortion blood smears were studied for fetal-maternal hemorrhage. Results showed that this may occur even in early suction termination. The significance of these findings was discussed in relation to the cost-effectiveness and the dosage of anti-Rho (D) globulin administered to patients.


Superior ultra-audiometric hearing: a new type of hearing loss which correlates highly with unusually good speech in the "profoundly deaf".

This paper reports 42 severely-to-profoundly deaf subjects, 6 of whom have better hearing in the range of 8 to 14 kHz than below 8 kHz. Data on speech capabilities in these six subjects suggest that this ultra-audiometric range may contribute to their speech comprehension and control.


Low-frequency harmonic acceleration as a test of labyrinthine function: basic methods and illustrative cases.

These preliminary findings reveal that low-frequency harmonic acceleration can be used to detect unilateral peripheral deficits that agree with caloric findings. However, the responses to sinusoidal acceleration are less variable than the caloric responses and allow one to more closely evaluate changes in pathology with time. Therefore, it appears that harmonic acceleration provides additional information that is useful in confirming other test results and that a complete otoneurologic evaluation should include this type of rotational testing.


Potentiation of kanamycin ototoxicity by a history of noise exposure.

Chinchillas were exposed to a noise band (1,414 to 5,656 Hz, 100-dB sound pressure level [SPL] for one hour) and treated with kanamycin (150 mg/kg a day until hearings loss was noted at 6.0 kHz) either separately, simultaneously, or sequentially. Simultaneous noise and kanamycin resulted in interactive potentiation of threshold shift and cochlear pathologic condition. Kanamycin treatment two months after noise exposure produced similar potentiation. No interaction was seen when noise exposure occurred one month after kanamycin treatment.


Sudden blindness secondary to injections of common drugs in the head and neck: I. Clinical experiences.

Several cases of sudden, irreversible blindness have been reported in the world literature following injections of various drug combinations in the head and neck. The common feature these drugs have is their capacity to either produce direct neurotoxic effects or embolic phenomena. Two new cases which resulted from injection of the combination of a depo or long-acting corticosteroid (methylprednisolone acetate, 40 mg) and a local anesthetic and epinephrine or penicillin were added to the growing world literature. The ocular and systemic pathologic findings are described and important questions are raised as to the pathophysiology. The need for an animal model experiment to answer as many of these questions as possible is emphasized.


Sudden blindness secondary to injections of common drugs in the head and neck: II. Animal studies.

The sudden occurrence of unilateral and bilateral blindness, as reported in the literature from the personal experiences of numerous qualified investigators, occurring in humans and producing such catastrophic effects seems to mandate experimental effort to try and answer three basic questions: (1) Can an animal model be found which will demonstrate similar retinopathy for study? (2) If such a model is found, what mechanisms are involved in the production of the retinal pathologic changes? (3) What are the characteristics of the drug or drug combinations necessary to produce these pathologic changes?


XXXIII Wherry Memorial Lecture. Head and neck surgery---an evolution over 30 years.

This lecture portrays a 30-year span in the history of head and neck surgery in otolaryngology, which the author experienced from its beginning, and describes the multiple events that have evolved in its transition to maturity.


The auditory pathology of anoxia.

A case of anoxic encephalopathy is reported, with study on a whole-auditory-pathways basis, and the method of processing tissues is outlined. Pathologic changes are found throughout the central part of the auditory pathway. The importance of including the superior ventral cochlear nucleus (SVCN) with cochlear structures in correlating findings with audiometric data is supported. The previously advanced tonotopic frequency pattern, with zonal vulnerability, of the spheroid cells of SVCN is supported.


Injury to the facial nerve associated with the use of a disposable nerve stimulator.

Clinical observations and experimental data from this study support the thesis that the disposable Weck nerve locator/stimulator may induce neural damage. This potential damage may cause at least a temporary paresis. Although more study is required to better document the method, degree, and factors influencing injury, we believe that enough evidence is present to induce caution and warrant further study. We recommend that the stimulators be used with caution on the lowest setting possible and with as little contact with the nerve as possible.


Tinnitus aurium: an approach to classification.

Tinnitus aurium is the single term used by professionals to describe a multiplicity of auditory experiences. An attempt to correlate tinnitus pitch, loudness, and spectral composition (noise vs pure tone) with audiometric data and subjective impressions is described, and a process for classifying tinnitus is presented. Preliminary results of tests on 40 patients are discussed and certain tendencies noted. The author recommends that all professionals obtain more complete information about their patients' tinnitus.


Partial or total eighth nerve section in the treatment of vertigo.

Partial vestibular (singular) neurectomy under general anesthesia through a postauricular approach is an effective method of relieving incapacitating benign positional vertigo, as is the case in 14 of 16 patients (87%) so treated. Middle fossa vestibular neurectomy appears to be a worthwhile procedure to deinnervate the peripheral vestibular system while preserving hearing. The results of 27 middle fossa vestibular neurectomies indicate relief of vertigo in 85% of the patients. The results of treatment on 44 patients undergoing transmeatal-cochleovestibular neurectomy indicated that vertigo was relieved in 19 of 23 (82%) with Meniere's disease and improved in 50% of the patients with post-stapedectomy vertigo and sensorineural hearing loss. Tinnitus was cured or markedly improved in 80% of the patients with Meniere's disease and 70% of the patients with post-stapedectomy sensorineural hearing loss and tinnitus. The transmeatal-transcochlear approach to the internal auditory canal offers advantages over the transmeatal labyrinthectomy or translabyrinthine approach to the internal auditory canal.


Microcauterization in reconstructive surgery of the larynx.

The increased interest in microcauterization is related to its simplicity, accuracy, and economy. Because of its intrinic nature, microcauterization has been found to be a suitable method in the removal of cicatricial bands from the larynx, even in those patients whose larynges are difficult to expose. Some endolaryngeal suturing techniques have been developed and successfully used in combination with microcauterization in the conservative management of difficult laryngeal problems, including a congenital interarytenoid cleft. A combination of this technique has also been successfully employed in the prompt rehabilitation of a meaningful group of patients afflicted with bilateral abductor paralysis of the vocal cords.


A new method for determining impulsive time constants and their application to clinical data.

We have developed an accurate, convenient method for determining unique values of vestibular time constants from impulsive tests. The method was used to determine the mean values and standard deviations of 36 normal subjects. A comparison between these normal values and data from patients with cerebellopontine (CP) angle tumors or unilateral peripheral vestibular lesions showed no significant difference in the values of the time constants. We conclude that shape-descriptive parameters such as time constants cannot differentiate between subjects and patients.


Vestibular system abnormalities in otosclerotic subjects.

A technique to quantify the tandem Romberg test (posturography) was used to study ten patients with otosclerosis before (series 1), 48 hours after (series 2), and between two to four months after (series 3) a stapedectomy. The results were analyzed by power spectrum analysis and then compared to findings from electronystagmographic testing performed with series 1 and 3. There was no significant change in the electronystagmography (ENG) test findings between series 1 and 3. Posturography, however, demonstrated an uncompensated vestibular pattern in the immediate postoperative period which, after two months, converted to a compensated vestibular pattern. Posturography serves as a useful quantitative test for the study of patients with balance disorders because the procedure supplements rather than complements the ENG. In addition, posturography detects vestibular reflex abnormalities in stapedectomized patients two months afterwards. Other testing modalities have not consistently demonstrated this postoperative vestibular system instability.


Teratocarcinoma of the ethmoid sinus: review of literature plus a new case report.

We report a third case of an unusual maligant neoplasm of the paranasal sinuses in a 60-year-old woman. Similar cases have been previously reported and called malignant teratoma. In consultation with Ackerman (written communication, February 1976) we propose the term "teratocarcinoma" and believe this is to be a more descriptive term and less likely to be confused with the generic term "teratoma," which is a benign tumor.


A method for evaluating vestibular control of posture.

Tests that measure the patient's ability to control his posture generally have failed to yield clinically useful information about vestibular function. The primary reason for this failure is that postural control does not depend on vestibular function when visual and proprioceptive cues are available. To test vestibular function, one should use a procedure that forces the patient to rely on vestibular cues by eliminating cues from these other sensory systems. Such a procedure is described. Vision is eliminated by eye closure, and proprioceptive cues are minimized by rotating the supporting surface to null changes in ankle angle. Data are presented which show that postural responses are complex, but that they appear to conform to the pattern originally observed by Nashner. A method potentially capable of separately evaluating semicircular canal and otolith function is described.


Lethal rhinocerebral phycomycosis in a healthy adult: a case report and review of the literature.

A lethal case of rhino-orbital-cerebral phycomycosis (mucormycosis) in an otherwise healthy man is presented. The clinical, radiologic, and ante mortem surgical pathology associated with microbiologic examinations failed to yield the diagnosis of fungal infection as the cause of a clinical presentation of acute sphenoid sinusitis with a fulminant cavernous sinus thrombosis. No similar case report was found in review of the literature. There is a need for a high degree of suspicion in this condition to improve the uniformly poor prognosis in this devastating infectious disease. Emphasis is placed on the necessity for early tissue or microbiologic diagnosis with appropriate histologic stains and fungal cultures. Treatment consists of extensive surgical excision of all necrotic or questionably viable tissue in conjunction with alternate-day amphotericin B therapy.


Non-Hodgkins lymphoma of the infratemporal fossa: a case report.

Lymphomas are statistically the second most common malignant tumor of the head and neck, following squamous cell carcinoma. They may present in the cervical lymph nodes or in extranodal areas. This paper presents an unusual case of a non-Hodgkins lymphoma that presented in the infratemporal fossa of a 25-year-old woman. The anatomy of the infra-temporal fossa is reviewed, and evaluation and therapy of lesions in this area are discussed.


Postauricular Kimura's disease.

Angiolymphoid hyperplasia with eosinophilia (Kimura's disease) is a relatively uncommon subcutaneous lesion, which can be confused with angiosarcoma. A case is presented. The differential diagnosis and therapy are discussed.


Liposarcoma of the maxilla.

A clinically appearing, well-encapsulated lipoma was locally excised from the right posterior upper buccal gingival sulcus of a 24-year-old man and diagnosed histologically as pleomorphic liposarcoma. A right maxillectomy with preservation of orbital function was followed by 5,000 rads of planned postoperative radiation therapy. Four months later the tumor recurred outside of the original site, which has been controlled by further radiation and chemotherapy to these areas.


Transpalatal excision of the odontoid process.

A patient with platybasia of the skull and temporomandibular joint ankylosis is presented. Relief of brain stem compression by the impingement of the odontoid through a soft, hypoplastic clivus was done by first doing a mandibular condylectomy to open the mouth. A transoral-transpharyngeal route was then employed to excise the odontoid process.


An alternative approach to the pterygopalatine fossa by removing the mandible and immediately replacing it.

A case is presented with a child with a desmoid tumor of the pterygopalatine fossa in which approximately a third of the mandible including the condyle was removed for exposure. The trimmed mandibular segment was then returned to position with a fascia cap over the condyle and intermaxillary fixation was instituted. The graft was followed by serial roentgenogram over five years. The graft took completely, grew with the patient, and resulted in normal dental occlusion and normal mandibular excursion.


Olfactory groove meningioma with paranasal sinus and nasal cavity extension: a combined approach.

A 58-year-old man had an enlarging right fronto-orbital mass. A biopsy specimen of a right nasal cavity tumor was reported as meningioma. Preoperative evaluation including skull roentgenograms, tomograms of the paranasal sinuses, brain scan, computerized axial tomography, and carotid angiography substantiated a large subfrontal mass with paranasal sinus and orbital extension. A combined approach through a right frontal craniotomy and right lateral rhinotomy was used for a complete removal of this tumor. A review of the literature is contained herein.


Actinomycosis of the larynx and pharynx.

This paper presents a case report of a 67-year-old man who was seen in the Otolaryngology Clinic, University of Wisconsin Medical Center with a seven-month history of dyspnea and laryngeal stridor. On examination there were several slightly tender firm submucosal nodules in the soft palate and left tonsilar area and a 1.5-cm polypoid subglottic mass arising from the body of the cricoid cartilage. Because of the marked airway obstruction, a tracheotomy was necessary. The laryngeal polypoid mass was removed and biopsies were obtained from the submucosal nodular masses of the palate. Microscopic examination of the tissue revealed the lesions to be caseating granulomas, and actinomycosis was identified on the cultures. The patient received long-term penicillin therapy and has remained asymptomatic. A discussion of the biologic and clinical aspects of actinomycosis is included. A review of the literature revealed only one other description of endolaryngeal actinomycosis.


Three simultaneous neoplasms of the larynx.

A 39-year-old man had three coexistent neoplasms of the larynx, squamous papilloma, verrucous carcinoma, and squamous carcinoma. In our review of the English literature, we could not find a similar case report. The potential transformation of benign laryngeal papilloma to verrucous carcinoma and infiltrating squamous cell carcinoma is discussed.