Cycloalkanoindoles. 2. 1-Alkyl-1,2,3,4-tetrahydrocarbazole-1-ethanamines and related compounds. Potential antidepressants.

The synthesis is described of a series of cycloalkanoindoles, comprising tetrahydrocarbazoles, a cyclopentindole, and a cycloheptindole, all bearing an ethanamine side chain at position 1. The acute toxicities of these compounds were evaluated, as well as their potential antidepressant properties, using tests based on the prevention of ptosis induced by reserpine and tetrabenazine. 9-Ethyl-N,N1-trimethyl-1,2,3,4-tetrahydrocarbazole-1-ethanamine (AY-24 614) was found to be the most potent analogue, having an ED50 of 0.12 mg/kg ip in preventing reserpine-induced ptosis in mice and an ED50 at 3.3 mg/kg ip in preventing tetrabenazine-induced ptosis in rats.


Biologically oriented organic sulfur chemistry. 14. Antiinflammatory properties of some aryl sulfides, sulfoxides, and sulfones.

To extend earlier work, to examine the possibility that certain sulfoxides might serve as counterparts of amines in receptor-site interactions, and to add to the little information available about sulfoxides in medicinal chemistry, sulfoxides were prepared of the general structure XArS(O)C6H4(CHR)nCO2H, together with the sulfides and some of the sulfones. The products were evaluated as antiinflammatory agents by carrageenan-edema inhibition and uv-erythema inhibition. Four of the compounds had activity roughly comparable to aspirin or phenylbutazone in one or the other of these assays (2a-c, 3b). Sulfoxides did not seem especially promising as a class and usually were less active than the corresponding sulfides. The two most interesting compounds in these assays, o-(phenylthio)phenylacetic acid (2b) and its sulfoxide 3b, had no significant activity in adjuvant arthritis. Hydrogen-bonding effects are indicated in certain of the acids by their absence in the corresponding esters.


Synthesis of aziridinylallylaminophosphine oxides and sulfides as potential adjuvant cancer chemotherapeutic agents.

Bis (1-aziridinyl)(hexahydro-1H-azepin-1-yl)phosphine sulfide, an active anticancer agent with low hematopoietic toxicity in animals and man, was recommended several years ago for breast cancer adjuvant chemotherapy as an alternate drug to thiotepa. This hope had led to the syntheses of aziridinylallylaminophosphine oxides or sulfides (compounds I-XVII) in our laboratories. The resurgent interest in this area of cancer chemotherapy encouraged us to report our synthetic work as well as their evaluation as both anticancer agents and insect chemosterilants. Based on observed antitumor activity in animals, low chemosterilant activity in female species (insects and rats), and histochemical observation of tissue toxicity in rat testes but not in ovaries, these new agents are of potential interest to the breast cancer adjuvant chemotherapy program.


Synthesis and properties of 2-S-(N,N-dialkylamino)ethyl)thio-1,3,2-dioxaphosphorinane 2-oxide and of the corresponding quaternary derivatives as potential nontoxic antiglaucoma agents.

A new series of cyclic organophosphorus esters, 2-S-[2'-N,N-dialkylamino)ethyl]thio-1,3,2-dioxaphosphorinane 2-oxide and their quaternary derivatives, was synthesized and studied as potential antiglaucoma agents. Thes compounds inhibit acetylcholinesterase (E.C.3.1.1.7)at a bimoecular rate constant (ki) in the range of 10(3)-10(4) M-1 min-1. Values of the affinity (K) and phosphorylation (k') rate constants for this enzyme indicate that k' is responsible for the relatively low values of ki as compared with similar data for the open-chain analogues, O,O-diethyl phosphorothiolates (10(6) M-1 min-1). The mammalian toxicity of the new compounds in terms of acute LD50 values in mice is 1-3 x 10(3) less than that of phospholine, an open-chain analogue. In an initial clinical trial, one member of the new series (alkyl = C2H5) caused a significant decrease of intraocular pressure in aphakic glaucoma, while phospholine proved to be ineffective.


Benzodipyran derivatives with antiallergic activity.

The synthesis and antiallergic activity of a number of benzodipyrandicarboxylic acids are described. Antiallergic activity of the compounds was determined using the homologous passive cutaneous anaphylaxis (PCA) reaction in the rat. The structural requirements for activity in the PCA screen are discussed. In this test system the linear benzodipyrans are more active than their angular analogues.


Esters of N-tert-butylarterenol. Long-acting new bronchodilators with reduced cardiac effects.

The preparation of various esters of N-tert-butylarterenol is described. Esterification of the phenolic OH groups has increased bioavailability, prolonged bronchodilation, and reduced tachycardia. The substitution of aromatic esters compared with simple aliphatic esters improved markedly these pharmacological properties. Of a number of esters tested, compound 45 (bitolterol) demonstrated the most favorable pharmacological properties as a bronchodilator. Its long duration of action and significant bronchodilator-cardiovascular separation are briefly described.


Synthesis of 1- and 2-substituted indazoles as anthelmintic agents.

Selective synthesis of 1- and 2-acyl-, alkoxycarbonyl-, and carbamoylindazoles are described. Spectroscopic data which were the basis for structural assignments are presented. These compounds, particularly methyl 2H-indazole-2-carboxylate and N-heptyl-N-methyl-2H-indazole-2-carboxamide, lack the spectrum of anthelmintic activity of the benzimidazole and benzotriazole anthelmintics to which they are structurally related.


Synthesis of 1-(4-thio-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide.

The synthesis of 1-(4-thio-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (3) is described. The acid-catalyzed fusion procedure with 3-cyano-1,2,4-triazole and 1,2,3,5-tetra-O-acetyl-4-thio-D-ribofuranose provided 3-cyano-1-(2,3,5-tri-O-acetyl-4-thio-beta-D-ribofuranosyl-1,2,4-triazole (2) which was converted with NH4OH to 3. In contrast to 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (1), the 4'-thio nucleoside 3 did not exhibt significant antiviral activity in vitro.


Synthesis and some pharmacological properties of deamino(4-threonine,8-D-arginine)vasopressin and deamino(8-D-arginine)vasopressin, highly potent and specific antidiuretic peptides, and (8-D-arginine)vasopressin and deamino-arginine-vasopressin.

Deamino[4-threonine,8-D-arginine]vasopressin (dTDAVP), deamino[8-D-arginine]vasopressin (dDAVP), [8-D-arginine[vasopressin (DAVP), and deamino-arginine-vasopressin (dAVP) were synthesized by the solid-phase method and tested for their biological activities. dTDAVP has an antidiuretic potency of 793+/-95 units/mg and undetectable vasporessor activity, less than 0.02unit/mg. The antidiuretic-pressor (A/P) ratio of dTDAVP is greater than 39 000. dDAVP has an antidiuretic potency of 1200+/-126 units/mg and a vasopressor potency of 0.39+/-0.02; its A/P ratio is thus 3000. DAVP has an antidiuretic potency of 253+/-44 units/mg, a vasopressor potency of 1.1+/-0.04 units/mg, and an A/P ratio of 240. The A/P ratios of dDAVP and DAVP are much higher than those originally reported. dAVP has an antidiuretic potency of 1745+/-385 units/mg, a vasopressor potency of 346+/-13, and an A/P ratio of 5; values are in general agreement with those in the literature. Threonine subsitution has thus brought about a significant enhancement in antidiuretic specificity, a finding entirely consistent with earlier observations that enhancement of lipophilicity at position 4 alone or in combination in arginine-vasopressin can lead to enhanced antidiuretic specificity.


Effect of chain length on critical micelle formation and protein binding of quaternary ammonium compounds.

The micelle formation tendency (log 1/CMC)) of a series of alkyldimethylbenzylammonium compounds is shown to be linearly dependent on the alky chain length, indicating no curling of the side chain up to C19. Protein binding of these charged molecules on the primary binding site for sulfaethiodole is shown to be parabolically dependent on the chain length with an optimal chain length around C16.


2-Azabicyclo (2.2.2)octane analogues of the prodine analgetics.

The synthesis and analgetic activity of analogues of prodine-type analgetics in which the conformation of the piperidine ring is restricted in the boat form using the 2-azabicyclo (2.2.2)octane nucleus are reported. One of these analogues, 2-methyl-6-trans-phenyl-6-cis-propionoxy-2-azabicyclo (2.2.2)octane (3), showed significant analgetic activity (ED50 equals 3.1 mg/kg).


Biological activity of C-terminal partial sequences of substance P.

Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) and the C-terminal partial sequences down to the tripeptide were synthesized by a solid-phase method. These peptides were assayed for vasodilator, spasmogenic, and venoconstrictor properties using three preparations, viz. the hind limb blood flow of the dog, isolated guinea pig ileum, and the isolated rabbit ear vein. The tripeptide and tetrapeptide possessed weak vasodilator properties only but no activity was detected on the other less sensitive preparations. The pentapeptide produced appreciable spasmogenic and vasoactive effects. Sequences of six or more C-terminal amino acids were able to elicity activity at comparable doses to that of the parent endecapeptide; however, the activity did not increase regularly with the chain length. In each assay preparation the octapeptide was the most potent peptide. It was twice as potent as substance P on a molar basis in the guinea pig ileum but the enhancement of activity beyond that of substance P was less pronounced in the vascular preparations.


Cerebellar contributions to the Papez circuit.

Cerebellar influences on the various substructures in the Papez Circuit are indicated by the following. 1. Anatomical studies indicate that the major midbrain areas to which this circuit projects are : 1) ventral tegmental area; 2) interpeduncular area; and 3) periaqueductal gray areas; and these same areas project back to the limbic system. There are projections to these regions from the cerebellar nuclei, as indicated by terminal degeneration studies which show that cerebellar nuclei connect, mostly by fine fibers, with a continuum of cells located on either side of the midline in the ventral tegmentum of the midbrain. Observations that the cerebellum also projects to the locus ceruleus (NA system) and VTA (DA system) indicate that cerebellar influences can also reach the limbic areas via the catecholamine fiber bundles. 2. Electrophysiological studies indicate that vermiam and fastigial stimulation induce evoked responses in the basolateral amygdala, the hippocampus, and the septum, with latencies to the peak of first wave ranging from 4 to 8 msec and to the second wave of 16-29 msec. Citations from the physiological literature indicate that electrical stimulation of the cerebellum, especially the vermis, can modify a wide range of responses which involve functional activities of either the sympathetic or parasympathetic nervous systems. 3. Studies on electrically induced afterdischarges in the septum, hippocampus, and amygdala indicate that cerebellar stimulation can shorten the duration of or terminate the afterdischarges, and the site of lowest threshold is the midline cortex. Focal cooling of the vermis promotes prolongation of the afterdischarges as does pretreatment of animals with 6-OH dopamine. Chemical lesions in the catecholamine system induced by 6-OH dopamine reduce the effectiveness of the cerebellar stimulation, as do lesions of nucleus fastigii. These data are interpreted to indicate that the cerebellum can exert a tonic suppressor (inhibitory?) influence on substructures within the Papez Circuit. 4. Citations from animal behavioral studies indicate that electrical stimulation of the anterior cerebellum can induce responses such as arousal, predatory attack, and feeding which mimic those obtained by amygdaloid stimulation. Fastigial stimulation can produce drowsiness and EEG changes which resemble the sleep patterns resulting from stimulation of the ventral amygdala.


Behavioral effects and binding affinities of two stereoisomeric psychotomimetic glycolates.

A comparison was made of the behavioral effects in cats of the dextro and levo isomers of 3-quinuclidinyl benzilate (QB), using a special computer-controlled program. Such psychophysical parameters as rate of response and tendency to use the left or right paw for lever pressing were used primarily to evaluate drug efficacy. The drug did not alter auditory threshold or the percentage of errors in lever pressing. The l-isomer was found to be at least 100 times as potent as the d-isomer, the effects of both being qualitatively similar. After a single dose of 5 mug/Kg of 1-QB, the cats' performance did not return to normal until 5-7 days later. Pretreatment of the cats with a dose of 2 mg/Kg of atropine, an antimuscarinic agent, did not prevent the behavioral effects of 1-QB. The binding affinity of two isomers for synaptic membranes and phosphatidyl serine was identical.


Origin of endocrine-metabolic changes in the weanling rat ventromedial syndrome.

Destruction of the ventromedial hypothalamic nuclei (VMN) in the weanling rat without injury to the median eminence results in a series of somatic, endocrine, and metabolic changes that are characterized by normal food and water intake but decreased linear growth, normal body weight but increased carcass fat and reduced carcass protein, lean body mass, and water. The endocrine alterations comprise hyperinsulinemia in the face of normoglycemia, hypertriglyceridemia and hypercholesterolemia and reduced growth hormone levels. The metabolic changes include greater oxidation of glucose and incorporation into lipid and reduced palmitate oxidation but increased incorporation into lipid. Weanling rats with VMN lesions are normophagic in absolute terms, relative to body weight and per metabolic unit, but their nocturnal feeding and weight gain cycles are disrupted and their locomotor activity is reduced. The VMN are involved in the long-term control of feeding - as in the mature rat - as shown by intragastric preloading studies and dietary density manipulation, glucose preference tests and intraperitoneal injections with glucose. Hyperinsulinemia and hypertriglyceridemia are present four days after the VMN operation in the presence of subnormal food intake and plasma glucose levels. Manipulations of the fat content of the diet revealed that the hyperlipidemia is of both endogenous and exogenous origin and that lipoprotein lipase is increased; a 48-hour fast reduced the hyperlipidemia to control levels, however. This suggests that weanling VMN rat tissue may have an impaired ability to take up circulating lipid. An increased incorporation of glycerol into lipid may be due to induction of glycerokinase by hyperinsulinemia. Adipose tissue of weanling VMN rats showed glycerokinase by hyperinsulinemia. Adipose tissue of weanling VMN rats showed neither depressed lipolysis nor diminished lipolytic activity per milligram of tissue protein. Glucose oxidation and incorporation into adipose tissue is increased in several tissues in vitro and there is enhanced glucose disappearance from plasma and incorporation into tissue lipids in vivo. These changes develop within a short time after lesion production and persist at least partially up to six months: glucose utilization in liver increases already four hours after the operation whereas it takes 72 hours to commence in adipose tissue. Insulin resistance is not apparent either in vivo or in vitro. The decreased growth hormone levels are not critical to the metabolic changes, nor is the hyperinsulinemia totally necessary. The metabolic changes also appear on several different types of diet and persist with fasting. The latter does not reduce insulin sensitivity of VMN rat tissues, wheras it does so in normal rats. Mature rats developed the same metabolic changes even in the absence of hyperphagia. The metabolic alterations can be blocked by pharmacologic doses of glucocorticoids, but are enhanced by the administration of estrogen...


Liver function tests and electrophoretic pattern of serum protein in hepatic amoebiasis.

The liver function tests and the electrophoretic pattern of serum protein in a series of 11 patients admitted to Bernhard Nocht Institut with hepatic amoebiasis were reviewed. A constant pattern of hypoalbuminaemia and elevated alpha2 globulins were demonstrated in all patients. LDH enzyme levels were raised in all cases admitted with amoebic liver abscess. The pathogenesis of these disturbances was discussed.


Parasitology survey in northern Sumatra, Indonesia.

A parasitology survey was conducted in five villages in North Sumatra, Indonesia. A total of 3,207 blood smears, 2,066 stool specimens and 969 sera were examined. Sixty (1.9%) inhabitants had malaria (Plasmodium vivax 41, P. falciparum 19), and 20 had Brugia malayi microfilaraemia. The most common intestinal helminths were Trichuris trichiura (87%), Ascaris lumbricoides (75%) and hookworm (58%). Other helminths found in low numbers were Enterobius vermicularis, Strongyloides stercoralis, Taenia sp., Fasciolid, Dicrocoeliid and Echinostoma sp. eggs. Entamoeba coli (25%) was the most common intestinal protozoa followed by Endolimax nana (8%), Entamoeba histolytica (7%), Giardia lamblia (6%), Iodamoeba bütschlii (5%), Entamoeba hartmanni (1%) and Chilomastix mesnili (1%). The amoeba prevalence rate was 31 per cent. Testing of sera for Entamoeba histolytica and Toxoplasma gondii antibodies by the indirect haemagglutination test demonstrated positive reactors in 13 per cent and nine per cent of the population respectively. The greatest number of seropositives for Toxoplasma gondii was at elevations of sea level to five meters and the lowest number at elevations of 5OO-1,000 meters.


Some aspects of cutaneous leishmaniasis in Riyadh. Saudi Arabia.

One hundred and sixty nine out of 310 outpatients of Riyadh's hospitals and 104 out of 209 inhabitants from El Kharj showed Leishmania bodies in smears obtained by puncture of indurated edge of sores. Collection of sand flies yielded P. papatasi, Paraphlebotomus caucasicus and S. squamipleuris. The results were discussed.


Reovirus-specific polypeptides: analysis using discontinuous gel electrophoresis.

The electrophoretic analysis of reovirus-specific polypeptides in infected cells using a discontinuous gel system has allowed the resolution of additional viral-specific polypeptides, including one large-sized gamma3 and two (or possibly three) medium-sized (mu3, mu4, mu5(?)) species. The proteins designated mu0, sigma1, and sigma2 based on electrophoretic mobility in gel systems containing phosphate-urea correspond to mu4, sigma2, and sigma1, respectively, when analyzed in systems containing Tris-glycine. It is likely that protein modifications (phosphorylation and glycosylation) are responsible for at least some of these differences.


Temperature-sensitive mutants of reovirus type 3: evidence for aberrant mu 1 and mu 2 polypeptide species.

An analysis of reovirus-specific polypeptides in cells infected with temperature-sensitive mutants under permissive and nonpermissive conditions revealed the presence of (i) all the known viral polypeptides and (ii) aberrant migration of the mu 1 and mu 2 polypeptides in four groups of mutants.


Detection of adenovirus type 2-induced early polypeptides using cycloheximide pretreatment to enhance viral protein synthesis.

(35S) methionine-labeled polypeptides synthesized by adenovirus type 2-infected cells have been analyzed by polyacrylamide gradient gel electrophoresis and autoradiography. Cycloheximide (CH) was added to infected cultures to accumulate early viral mRNA relative to host cell mRNA. This allowed viral proteins to be synthesized in increased amounts relative to host proteins after removal of CH and pulse-labeling with (35S)methionine. During the labeling period arabinosyl cytosine was added to prevent the synthesis of late viral proteins. This procedure facilitated the detection of six early viral-induced polypeptides, designated EP1 through EP6 (early protein), with apparent molecular weights of 75,000 (75K), 42K, 21K, 18K, 15K, and 11K. Supportive data were obtained by coelectrophoresis of (35S)- and (3H)methionine-labeled polypeptides from infected and uninfected cells, respectively. Three of these early polypeptides have not been previously reported. CH pretreatment enhanced the rates of synthesis of EP4 and EP6 20- to 30-fold and enhanced that of the others approximately twofold. The maximal rates of synthesis of the virus-induced proteins varied, in a different manner, with time postinfection and CH pretreatment. Since CH pretreatment appears to increase the levels of early viral proteins, it may be a useful procedure to assist their isolation and functional characterization.


Hybridization of mRNA from adenovirus-transformed cells to segments of the adenovirus genome.

Cytoplasmic viral-specific RNA from the 8617 line of adenovirus type 2 (Ad2) transformed rat cells was hybridized to DNA fragments derived either by Eco-RI or Sma-I restriction endonucleases. Three discrete classes of viral RNA (26S, 20S, and 15S) were detected by hybridization of total cytoplasmic RNA with the fragment, and all of these RNA molecules also hybridized to the much smaller Sma-E fragment of Ad2 DNA. Poly (A)-containing RNA (exposed to 90% formamide) contained only the 20S and 15S mRNA species, suggesting that the 26S RNA might be an aggregated species. Viral RNA of the same size derived from the same regions of the genome has not been detected in lytically infected cells, suggesting some change in the pattern of transcription or RNA processing of the Ad2 DNA in the integrated state.


Adenovirus type 12-specific RNA sequences during productive infection of KB cells.

The complementary strands of adenovirus type 12 DNA were separated, and virus-specific RNA was analyzed by saturation hybridization in solution. Late during infection whole cell RNA hybridized to 75% of the light (1) strand and 15% of the heavy (H) strand, whereas cytoplasmic RNA hybridized to 65% of the 1 strand and 15% of the h strand. Late nuclear RNA hybridized to about 90% of the 1 strand and at least 36% of the h strand. Double-stranded RNA was isolated from infected cells late after infection, which annealed to greater than 30% of each of the two complementary DNA strands. Early whole cell RNA hybridized to 45 to 50% of the 1 strand and 15% of the h strand, whereas early cytoplasmic RNA hybridized to about 15% of each of the complementary strands. All early cytoplasmic sequences were present in the cytoplasm at late times.


Isolation and characterization of temperature-sensitive mutants of adenovirus type2.

Fourteen temperature-sensitive mutants of human adenovirus type2, which differed in their plaquing efficiencies at at the permissive and nonpermissive temperatures by 4 to 5 orders of magnitude, were isolated. These mutants, which could be assigned to seven complementation groups, were tested for their capacity to synthesize adenovirus DNA at the nonpermissive temperature. Three mutants in three different complementation groups proved deficient in viral DNA synthesis. The DNA-negative mutant H2ts206 complemented the DNA-negative mutants H5ts36 and H5ts125, whereas mutant H2ts201 complemented H5ts36 only. Among the DNA-negative mutants, H2ts206 synthesized the smallest amount of viral DNA at the nonpermissive temperature (39.5 C). Data obtained in temperature shift experiments indicated that a very early function was involved in temperature sensitivity. In keeping with this observation, early virus-specific mRNA was not detected in cells infected with H2ts206 and maintained at  39.5 C. Prolonged (52 h) incubation of cells infected with H2ts206 at the nonpermissive temperature led to the synthesis of a high-molecular-weight form of viral DNA.


Characterization of adenovirus type 2 transcriptional complexes isolated from infected HeLa cell nuclei.

HeLa cell nuclei, isolated 17 h after infection with human adenovirus type 2 (Ad2), were treated with 200 mM ammonium sulfate. The extract (S200 fraction) contained 50 to 70% of the nonintegrated Ad2 DNA, which was in the form of nucleoprotein complexes. These complexes contained native, intact Ad2 DNA (with the exception of replicative intermediates) and could be partially purified and resolved by velocity gradient centrifugation. Using high-salt (200 mM ammonium sulfate) incubation conditions, more than 95% of the nuclear RNA polymerase activity belonged to class B. About 45% of the class B enzyme molecules bound to DNA in the nuclei (those "engaged" in RNA synthesis) were released from the nuclei in the form of Ad2 transcriptional complexes by treatment with 200 mM ammonium sulfate. At least 90% of the RNA synthesized in high salt in the nuclei or in the S200 fraction was Ad2 specific, and essentially all of this RNA was complementary to the l strand of Ad2 DNA. These findings are compatible with what is known about Ad2-specific RNA synthesis in vivo. The analysis of the RNA synthesized from partially purified transcriptional complexes supports the contention that its transcription is almost entirely asymmetric, and that the asymmetry observed in vivo is not a consequence of the rapid degradation of h-strand transcripts. The RNA synthesized in vitro in the absence of detectable RNase activity sedimented with a maximum size of 35 to 40S. Less than 5% of the nuclear or the S200 fraction RNA polymerase activity was class C when assayed under non-reinitiating conditions. Although much of the RNA synthesized by the class C enzyme was Ad2 specific, 5.5S virus-associated RNA was not the predominant product. The isolation of Ad2 DNA transcriptional complexes provides an attractive system for further characterizing the Ad2 DNA template used for transcription and for studying the regulation of the expression of the Ad2 genome during the productive infection cycle.


Oral methylene blue and the dissolution of renal calculi.

Oral methylene blue therapy was not effective in dissolving non-obstructive renal calculi in 26 patients but it may prevent new stone formation in patients with metabolically active urolithiasis. The use of methylene blue therapy in combination with other regimens having different mechanisms of stone inhibition is recommended to further improve results.


Operative nephroscopy.

Renal endoscopy has been made possible, practical and safe by technical advances in instrumentation. Operative nephroscopy has become a uniquely valuable adjunct to stone operations, especially for caliceal calculi, but does not permit the surgeon to dispense with operative x-rays. Furthermore, it has extended our horizons in the management of intrarenal hematuria and of low grade tumors of the renal collecting system. We suggest that the rigid right-angled nephroscope in use today be referred to as the Leadbetter nephroscope in recognition of that pioneer's original conception for its design.


Adult ureteral ectopia.

We report on 6 women with ureteral ectopia to emphasize the need for careful endoscopic examination in evaluating the entity. The clinical histories are unusual in that 1 of the 6 patients had classical symptoms of urinary incontinence. A discussion of the diagnosis and treatment of ureteral ectopia in such patients is presented.


Spontaneous urinary extravasation.

The diagnosis and management of 12 patients with spontaneous non-traumatic urinary extravasation are described. It is important to distinguish extravasation of the fornical backflow type from that owing to frank rupture of the diseased renal pelvis. Most cases of the former variety are caused by calculous ureteral obstruction and can be managed conservatively. Surgical intervention is indicated for the latter variety (frank rupture) and is based on the requirements imposed by the patient's clinical condition, the persistence of obstruction or extravasation, or the presence of complications of extravasation such as urinoma or abscess.


Flexible fiberoscopy of urinary conduits.

During the last 2 years 7 patients with intestinal urinary conduits, exhibiting symptoms of gross hematuria and ureteral stricture or other difficulty with the conduit, were examined with flexible fiberoptic endoscopes. The entire lumen of the intestinal conduit, all urinary-intestinal anastomoses and the bladder of 1 patient were visualized successfully. Retrograde pyelography was performed on 2 patients. In 4 of 7 patients we were able to demonstrate abnormalities that were not demonstrable by any other method.


Further observations on self-catheterization.

A non-sterile technique of intermittent self-catheterization was used for 218 patients with an inability to void in a normal fashion because of obstructive uropathy, decompensated detrusor or neurogenic bladder. Marked improvement was noted in urinary continence, urinary infection, renal function, bladder emptying and, perhaps most important, the mental and emotional status of the patient and/or parents. The extremely low incidence of complications and its therapeutic efficacy clearly make clean, intermittent self-catheterization an outstanding weapon in the urological armamentarium and a most persuasive reminder that host resistance is still the primary factor in the occurrence of infection.


Adrenergic and cholinergic stimulation and blockade of the human bladder base.

The response of muscle strips from the human anterior and posterior bladder base to autonomic stimulation and blockade was studied. The human bladder base, like that of the dog, possesses an abundance of cholinergic and alpha-adrenergic receptor sites. Neuropharmacologically, the musculature of the anterior base is similar to that of the posterior base (trigone plus detrusor musculature).


Treatment of rupture of the bladder.

Herein we review our 6-year experience with operative and non-operative treatment of bladder ruptures. Many ruptured bladders with extraperitoneal and intraperitoneal extravasation of urine can be treated without an operation and with less patient morbidity.


Vesicoureteral reflux following transurethral resection of bladder tumors.

Vesicoureteral reflux after transurethral resection of bladder tumors is a significant complication (19 per cent incidence in the present series). Although most patients with such reflux suffer no apparent ill effects renal destruction occurs in some. Other implications are discussed and the obligation for recognition of the reflux when it exists is emphasized. A simple technique for routine diagnosis is suggested.


Primary carcinoma of the female urethra.

The clinical and morphological features in 81 cases of carcinoma of the female urethra were reviewed. The over-all 5 and 10-year survival rate for the entire group was 32 per cent. Survival expectations for patients with squamous carcinoma, transitional cell carcinoma and adenocarcinoma were similar when analyzed according to stage and all cell types appeared to respond equally to irradiation. Prognosis was related directly to the clinical stage of the disease. A plea is made for more accurate assessment of the disease status. The high incidence of local recurrence noted for all forms of single modality therapy (46 to 64 per cent) suggests the need for clinical trials with combination preoperative irradiation followed by definitive surgical procedures.


Psychological screening of impotent men.

Rapid advances in methods of treating sexual impotence have produced concomitant demands for more specific diagnosis and determination of prognosis. Herein are presented guide lines for a rapid screening procedure that has diagnostic and prognostic utility. Use of 2 decisional rules for the Minnesota Multiphasic Personality Inventory, an easily administered and scored psychological test, can provide assistance to the urologic surgeon in determining the suitability of a candidate for a corrective operation. Case histories illustrate the value of this test in making treatment recommendations and assessing prognosis.


Paratesticular sarcomas: review of management.

Two patients with paratesticular sarcomas (1 leiomyosarcoma and 1 liposarcoma) are described, making the total number of cases reported 206. A review of the diagnosis and a critical analysis of the therapeutic approaches are presented.


Prophylactic antibiotics in transurethral prostatectomy.

In a prospective randomized study involving 90 uninfected patients undergoing transurethral prostatectomy it was found that routine postoperative use of prophylactic cephalosporins had no beneficial effect on the incidence of fever, hospital stay or major complications. Patients receiving cephalosporins had a significantly lower incidence of postoperative bacteriuria immediately after catheter removal and 1 month postoperatively.


Radiotherapy in the management of stage C carcinoma of the prostate.

A small number of patients with limited stage C carcinoma of the prostate have been treated with combined interstitial and external beam radiotherapy with gratifying results. Whereas more patients will have to be followed for at least 10 to 15 years to completely evaluate this modality of treatment, the results continue to encourage us in its use.


The continued evaluation of the effects of chemotherapy in patients with advanced carcinoma of the prostate.

The response and duration of survival were evaluated for patients with stage D relapsing prostatic cancer who were randomized to cyclophosphamide (cytoxan), 5-fluorouracil (5-FU) or standard therapy, or to subsequent chemotherapies. The chemotherapies on initial randomization were superior to the standard therapy in the number of responders and duration of response. Survival was longer for responders (stable or partial regression) on chemotherapy by comparison to responders (stable only) on standard therapy. The survival for patients receiving initial and crossover chemotherapy was significantly improved for patients who responded to therapy. Chemotherapy of advanced relapsing stage D prostatic cancer is more beneficially treated by specific chemotherapy as shown in this randomized study.


Current clotting concepts in urology.

A modern outline of the physiology of coagulation, a simple approach to the use of laboratory investigation for patients with possible clotting disorders in unexplained hematuria and several illustrative cases are presented. The diagnosis and management of localized fibrinolysis in the genitourinary tract and intravascular coagulation as possible causes of post-prostatectomy hemorrhage are discussed. A minimum of a platelet count, fibrinogen assay and, if possible, measurement of fibrinogen-related antigens should be obtained before administration of epsilon aminocaproic acid.


Electrosurgery burns and the urologist.

Investigations into the problems associated with electrosurgery machines have concentrated on protecting the patient from radio frequency burns. While protection of the patient is essential an equally serious and dangerous situation exists in protecting the surgeon, particularly the urologist during transurethral resection of the prostate. The 2 subtle causes of burns to the surgeon are reviewed--capacitive coupling and grounding paths that include the surgeon. Protection of the surgeon as well as the patient depends upon an awareness of the peculiar mating of high frequency current and the grounded environment of the operating room.


Informed consent: recent changes in the law.

Physicians have the legal duty to disclose all risks and consequences of a proposed procedure. This duty must be understood as a reversal of previous legal doctrine. Disclosure is adequate only when a patient has enough information from that disclosure to decide for himself which way he wants to go and what treatment he wants to choose from among the options available to him. Relevance of disclosure, not fullness, is the criterion of sufficiency. The idea that the doctor or the profession knows best what the patient should do has been rejected as a legal standard in the District of Columbia, California, New York, Wisconsin, Kansas and Rhode Island. It is expected that more states will follow this trend. The informed part of the doctrine of informed consent is only the tip of an iceberg of social change.


Postural detrusor hyperreflexia.

Postural changes in bladder function have been documented previously only in female incontinent patients without evidence of neurologic or urologic disease. In our study the syndrome of postural hyperreflexia is described in patients of both sexes having a variety of neurological disorders. The investigations showed impaired function of supraspinal control of the sacral micturition center.


Xanthogranulomatous pyelonephritis in childhood.

We report the tenth case of xanthogranulomatous pyelonephritis, which is a rare cause of supperative proliferative pseudo tumor in children. The disease is more segmental in the child than in the adult and should be considered in the differential diagnosis of renal masses. Early recognition and conservative operation can result in a permanent cure.


Extra-adrenal pheochromocytoma producing renal artery stenosis.

A case of extra-adrenal pheochromocytoma on the left side in relation to the left renal pedicle, producing renal artery stenosis, is described because of its rarity, and diagnostic and therapeutic problems. The pheochromocytoma was excised and the kidney was preserved.


Multilocular kidney disease: unusual angiographic appearance.

A case of multilocular kidney disease is presented and the unusual appearance of tumor vessels is emphasized. The occasional coexistence of multicystic kidney disease and renal cell carcinoma in adults also is mentioned.


Downward displacement of the left kidney caused by ectopic ovarian cyst developing in the subphrenic region.

A rare case of downward displacement of the left kidney caused by marked development of an ectopic ovarian cyst in the left subphrenic region is presented. Exact diagnosis could not be made preoperatively but a satisfactory result was obtained by removal of the cyst. Histological diagnosis of the tumor was serous cystadenoma arising from the left ovary.


Venous infarction of the testis owing to vena caval thrombosis.

A 37-year-old man presented with what appeared to be acute epididymitis but was later found to be venous infarction of the testis owing to vena caval thrombosis.


Study of hemodynamic changes with oxygen inhalation in VSD associated with pulmonary hypertension.

Pre- and postoperative pulmonary hemodynamic changes were studied in 28 cases with ventricular septal defect, in whom pulmonary-systemic blood pressure ratio was more than 70%. Pp/Ps decreased and Qp/Qs increased in majority of cases and Rp/Rs decreased in all cases after 100% oxygen inhalation. In survivors, Rp/Rs decreased to under 0.5 and Qp/Qs increased to more than 2.0 after oxygen inhalation or radical operation. In nonsurvivors, Rp/Rs decreased but stayed over 0.5, and Qp/Qs increased but stayed under 2.0. It is emphasized that when Rp/Rs falls down to under 0.5 after oxygen inhalation, it will be an enough indication for operation even pulmonary hypertension is so advanced in the ventricular septal defect.


Surgical indications and results for congenital cardiac anomalies associated with left to right shunt and severe pulmonary hypertension.

Prior to 1970, 35 patients of VSD with Pp/Ps of 0.8 or more were subjected to primary closure of the defect, resulting in 11 operative deaths. Since 1971, however, the surgical results have been much improved and 29 such patients were operated on without death. It has been considered the optimal time of elective closure of VSD with severe pulmonary hypertension is at the age of 1 to 3 years, however, if decrease in apical diastolic rumble and heart size are found, earlier operation less than one year of age is to be scheduled. Surgical indications and results of PDA, PDA with VSD, and ASD associated with severe pulmonary hypertension were also discussed.


The early and late effects of surgical closure of ventricular septal defects on pulmonary vascular dynamics.

In sixty patients who underwent closure of ventricular septal defect (VSD), cardiac catheterizations were performed before and late after surgery together with pressure measurements immediately after closure of the VSD during surgery. Pulmonary arterial mean pressure (PAm), pulmonary arterial systolic pressure to systemic arterial systolic pressure ratio (Pp/Ps), and pulmonary vascular resistance to systemic vascular resistance ratio (Rp/Rs) were measured and calculated. The patients were classified into 5 groups according to the preoperative Rp/Rs and Qp/Qs as was reported by Nakada: Group A: Rp/Rs less than 0.15, Qp/Qs larger than or equal to 1.8, Group B: Rp/Rs less than 0.15, Qp/Qs less than 1.8, Group C: 0.15 less than or equal to Rp/Rs less than 0.50, Group D: 0.50 less than or equal to Rp/Rs less than 0.85, Group E: 0.85 less than or equal to Rp/Rs. These groups were further divided into 3 groups respectively according to age at operation (less than or equal to 2 years, 3 or 4 years, 5 years less than or equal to). The averages of PAm, Pp/Ps, and Rp/Rs were within the normal range in Group A and B patients (normal pulmonary vascular resistance groups) irrespective to the age at operation  except the average of PAm before surgery. In Group C, D and E patients (elevated pulmonary vascular resistance group), these variables decreased immediately after closure of VSD, and further decreases were noted at the time of late catheterization. These variables, however, did not completely normalize even at that time. Among the patients operated upon at 2 years of age or less, the averages of these variables normalized immediately after closure of the VSD. When operated upon at 3 or 4 years of age, these variables decreased but did not normalize immediately after closure of the VSD and were found to be within the normal range at the time of late catheterization. When operated upon at 5 years of age or more, these variables decreased immediately after closure of the VSD, and further decrease was found at the time of late catheterization but mostly remained in the abnormal range even at this time. From the data obtained herein, the factors producing the pulmonary vascular resistances in respective age groups were discussed. The closure of VSD in patients with elevated pulmonary vascular resistance is recommended at the latest 4 years of age and preferably at 2 years of age or less, in order to obtain normal pulmonary circulatory dynamics after surgery.


The operability of patient with pulmonary hypertension judged from hemodynamic changes before and after surgery.

1) In congenital heart disease with pulmonary hypertension, the place for surgical correction still remains even with almost systemic PA pressure if R to L shunt ratio on lung scintigram is lower than 25%. 2) The patient with pulmonary hypertension in congenital heart disease younger than 3 years of age has wider acceptability for surgery compared to older patient. 3) In patients with mitral valvular disease, surgical correction seems to be indicated irrespective of PA pressure, if their preoperative U/L are lower than 2.4.


Cardiac lymph and contractility of the heart.

The transport mechanism of cardiac lymph with reference to the contractility of the heart was studied experimentally using a dye technique. An augmentation of cardiac contractility with or without hypoxia of the heart equally accelerated the transportation of cardiac lymph. The short staining time of the "cardiac node" correlated well to the augmented contractility of the heart and the long to the decreased contractility. Similar result was obtained in the dogs with surgical block and pacing at a rate of 100/min. This experiment suggests the importance of dynamical observation of cardiac lymph.


[Evaluation of the contractile function of the right ventricle in patients with mitral-tricuspid valve defect].

A comparative analysis is presented of the Sonnenblick contractility index, end-diastolic and systolic pressure in the right ventricle, cardiac index in 76 patients with mitral-tricuspid disease and with a mitral disease alone. Higher figures of the contractility index of the right ventricle were obtained in patients with an organic tricuspid defect with a predominance of insufficiency, than in those with mitral insufficiency and relative tricuspid insufficiency. The contractility index of the right ventricle decreases along with an increasing stenosis of the right venous ostium. The study has demonstrated that the patients with mitral-tricuspid defects tend to display a less distinct inotropic reaction to Digoxin as compared with those having a mitral defect alone.


[Certain aspects of the pathogenesis and prophylactic treatment of hypertensive crises].

The paper analyses the results of a study of the clinical peculiarities of the course of essential hypertension with crises, of the changes in the functional state of the central nervous system, and of some neuro-humoral systems of the human body. In most of the patients tending to develope frequent crises distinct changes were noted in the EEG that indicate dysfunction of the hypothalamic zone and of the reticular formation of the brain stem, their clinical course being characterized by significant astheno-neurotic disorders with autonomous dysfunction and cerebral angiodistonic disturbances. For the prevention of crises it is essential to conduct a pathogenetically substantiated and highly differentiated systematic therapy, as well as special measures aimed at increasing the endurance of the central nervous system, improving the circulation and metabolic processes in the brain, decreasing tnd hypothalamic structures of the brain, and correcting the dishormonal disorders.


[Reconstructive operations in surgical treatment of vasorenal hypertension].

The experience of 313 reconstructive operations performed in 289 patients with renovascular hypertension is analysed. The importance of choosing the surgical procedure with due regard of the etiology and extent of the pathological process is emphasized. The most effective and frequently employed reconstructive procedures consisted in the author's original technique of transaortic endarterectomy (232 operations), resection of the renal artery with reimplantation of the ostium into the aorta (19 operations), renal artery resection with an end-to-end anastomosis (23 operations). In cases of bilateral lesions of the renal arteries two-stage procedures are recommended, spaced 3-4 months apart. Reconstructive interventions on the single renal artery are described.


[Diagnosis and results of surgical treatment of arterial hypertension of endocrine-adrenal origin].

Surgery was undertaken in 149 patients with tumours or hyperplasia of the adrenal glands accompanied by high arterial hypertension, not infrequently of a malignant nature. An analysis is presented of some auxiliary methods of clinical diagnosis of pheochromocytomas (69 cases) and aldosteromas (56 cases). Data on the methods of topical diagnosis are presented, among which the authors believe tomography of the adrenals conducted against the background of pneumoretroperitoneum, and selective phlebography of the adrenals to be the best techniques. The immediate results of surgery for this grave form of hypertension are reported. The late results of the hypotensive effect of surgery are analysed in all 149 operated cases, the follow-up period ranging from 2 to 15 years.


[Method of quantitative evaluation of the reactivity of the microvessels to vasoactive substances in patients with hypertensive disease].

A method developed by the authors is described that consists in a quantitative test for the evaluation of the reactivity of the microvessels judging by the degree of changes in the resorption speed of isotopes from a tissue depot. In patients with essential hypertension an increased vascular reactivity was revealed with reference to angiotensin, noradrenalin and serotonin, as well as an increased duration of the effect of angiotensin. The highest vascular reactivity was noted in patients with stage II hypertension who have retained a hyperkinetic type of circulation.


[Effect of physical exercises on certain indicators of lipid metabolism in patients with hypertensive disease and renal hypertension].

The effect of physical exercises was studied with reference to the content of non-esterified fatty acids (NEFA), cholesterol and beta-lipoproteins, as well as catecholamines and lactic acid in 130 patients with essential and renal hypertension. The control group included 12 normal individuals. The physical exercises were conducted on a bicycle ergometer with a step-wise growth of the load by 150-300 kgm per each 4 min. The value of the maximal tolerated physical load was determined. It was decreasing parallel the progress of the disease. The conducted investigations demonstrated the presence of an inverse relationship between the initial blood level of beta-lipoproteins and cholesterol, on the one hand, and the value of physical load and capacity for work, on the other. The changes in the lipid metabolism parameters are distinctly connected with the activity of catecholamines and lactate concentration.


[Analysis of the reserve capacity of the myocardium in patients with hypertensive disease and its importance for disability evaluation].

The paper presents an analysis of the results of a comprehensive clinical and instrumental examination (poly- and apex-cardiography) of 156 patients with essential hypertension (Stages I, I-II and II, according to L.I. Fogelson's classification) and of 40 normal individuals, that was undertaken to study the functional state and the reserves of the left ventricular myocardium. The disorders in the functional state and the reduction of the reserve capacity were shown to progress along with the stage of the disease. The clinical and labour prognosis of the patients with essential hypertension depend on the character of its course, stage of the disease, degree of functional disorders and reserve capacity of the myocardium, as well as on the profession and labour conditions. The employment of a broad complex of cardiological diagnostic techniques at rest and following dosaged bicycle ergometric load helps to determine the clinical and labour prognosis with greater precision and more objectively, and to solve the problems of timely employment of hypertensive patients.


[Porto-caval transposition and the course of vasorenal hypertension].

The study concerns the effect of angiotensin II when infused into the systemic and portal blood flow upon the general and renal haemodynamics in normal dogs and in hypertensive animals, as well as the effect of the operation of porto-caval transposition upon the course of renovascular hypertension. When peptide is infused, at a rate that causes a moderate pressor effect, into the systemic blood flow of normal animals, an antidiuretic and antinatriuretic effect is obtained, in hypertensive animals--an increase of diuresis, natriuresis and a less distinct pressor effect are obtained. When angiotensin II is infused into the portal flow, a less distinct pressor and renal effect is seen in animals with renovascular hypertension. The operation of porto-caval transposition of the vessels results in a hypotensive effect in the animals with renovascular hypertension.


[Renal prostaglandins in DOCA-sodium chloride-induced hypertension in rats].

The changes in arterial pressure, sodium excretion, diuresis, and content of renal prostaglandins were studied in rats with COD-salt hypertension. The administration of DOC to rats with unilateral nephrectomy resulted in more distinct hypertension than in those with both kidneys preserved. Arterial pressure elevation was accompanied by a gradual reduction of renal prostaglandins concentration, the removal of one kidney causing an earlier and more distinct reduction of their content. Unilateral nephrectomy (without DOC administration) resulted in a reduction of prostaglandins concentration in the remaining kidney, but their total content in the medullar layer of this kidney practically did not change.


[Cytochrome system of myocardial mitochondria in patients with mitral valve insufficiency].

The content of cytochromes in the mytochondria of the papillary muscles and auricles of the left atria was studied by means of differentiated spectrophotometry in patients operated on for mitral valve insufficiency. A significant reduction of all cytochromes was noted in the papillary muscles of the left ventricle that depended on the stage of circulatory insufficiency. In cases of a protracted course of the disease a tendency towards a reduction in the content of all cytochromes, especially the a + a3 cytochrome, was noted in the papillary muscle. When the content of cytochromes in the myocardium was reduced, the number of cardiac complications in the postoperative period was much higher. A moderately expressed activity of the rheumatic process had no significant effect upon the content of cytochromes in the heart muscle.


[Changes of catecholamine content in the myocardium in thyrotoxicosis].

Experimental thyrotoxicosis was induced in rats and rabbits. The content of catecholamines was significantly decreasing in the myocardium of rabbits in the presence of severe thyroidine-induced toxicosis. The noradrenaline concentration was especially low in the ventricles. The histochemical examination of the myocardium of rats revealed a reduction of catecholamines fluorescence, which indicates a decrease in their amount in the adrenergic structures.


Method: melodic intonation therapy for aphasia.

Melodic intonation therapy (MIT), a method developed to assist the adult aphasic regain verbal communication, is presented with step-by-step procedures and suggestions. Also described is the type of patient for whom the technique appears most successful.


Utilization of an interrogative model to evaluate mothers' use and children's comprehension of question forms.

A study was conducted to determine the efficacy of utilizing Leach's interrogation model as a means for analyzing question types used by mothers and their children's responses to various interrogative forms. Data analyzed consisted of language samples obtained from three preschool children and their mothers during mother-child interactions plus each child's responses to a 90-item probe containing questions representing the 15 question forms delineated by the model. The interrogation model was an effective and reliable tool in the analysis of data. The question forms most frequently used by the mothers were (1) wh- interrogative nominal segment, (2) auxiliary + no infinitive, and (3) tag questions. All three subjects displayed similarities of performance in response to wh- interrogative nominal segment and auxiliary + no infinitive questions. Two of the subjects appeared capable of appropriately answering all of the question forms tested during the interrogative probe. Similarities of performance during the mother-child interaction and the interrogative probe were found to exist for two of the three subjects in certain categories. A high percentage of the questions posed by the mothers during the mother-child interactions were of forms which their children consistently answered appropriately during the interrogative probe.


Effects of stimulus presentation and instructions on pure-tone thresholds and false-alarm responses.

The effects of three instructional sets (conventional Carhart-Jerger, strict, and lax) and of two stimulus presentation methods (continuous tones, pulsed tones) on pure-tone thresholds and false-alarm responses were determined for 20 male subjects. False alarms were tallied during hearing measurement periods and during 30-second time-out periods totaling nine minutes of time-out per subject. Results showed that 50% of the subjects made false-alarm responses to some extent at 250, 1000, and 4000 Hz. Instructions and stimulus mode, along with frequency, affected the number of false alarms, but thresholds under the experimental conditions were unchanged. It is suggested that a method for assessing and controlling false alarms is an important clinical consideration.


Spectrographic comparison of two types of spastic dysphonia.

A spectrographic comparison of the voices of two patients with spastic dysphonia demonstrated differences in vocal characteristics. The voice of one patient was characterized by intermittent breathiness which appeared spectrographically as a breakdown in formant structure or as the addition of fricative fill superimposed upon resonance bars. The voice of the second patient was characterized by strain-strangle phonation which appeared spectrographically as widely and irregularly spaced vertical striations. The contrasting vocal characteristics of the two patients are compatible with the viewpoint that there may be two types of spastic dysphonia.


A tangibly reinforced speech reception threshold procedure for use with small children.

Forty normal-hearing children between 17 and 56 months were tested using a new method for determining speech reception thresholds. The words employed were names for parts of a device that was in the form of a colorful clown. The device automatically rewarded the child with a small piece of candy each time he pressed the part of the clown that had been announced through the sound field system of a speech audiometer. Results showed that operant conditioning speech audiometry using tangible reinforcers is feasible for small children. Both boys and girls can be tested accurately by this method down to age two and one-half years.


Sign language acquisition in a mute autistic boy.

A mute autistic boy learned to communicate extensively through American Sign Language. Over a six-month period he produced many spontaneous signs and sign combinations, and analyses of child's sign combinations indicated the presence of a full range of semantic relations. Further evidence of conceptual progress was provided by the child's increased score on the Peabody Picture Vocabulary Test. In addition, parents' and teacher's reports indicated that the child's social behavior improved. The extent of the boy's linguistic progress and associated improvement in social behavior markedly exceeds that usually reported for mute autistic children.


Communication problems in hearing children of deaf parents.

Fifty-two children who had deaf parents and were thought to have normal hearing were evaluated for speech, hearing, and language problems. Standardized tests, audiological evaluations, and informal conversation and play techniques were used. Of the 52 children of deaf parents, less than half were considered to be developing speech and language normally and 12% had previously undiagnosed hearing loss. The prevalence of speech and language problems and hearing losses is higher in this population than in the population at large. The children appeared to be using two systems to communicate, one with hearing people and one with the deaf. Of the children having some speech and language difficulty, approximately half had problems that were not associated with other known physiological or environmental factors that might affect speech and language. Although there were no children of intelligible mothers who had speech and language problems, there were children developing normally who had parents whose speech intelligibility was poor. Contrary to indications in the literature, speech and language problems did not disappear after the children entered school. A large number of school-age children as well as preschoolers appeared to be having speech and language problems. The amount of time spent with hearing adults during the preschool years or the presence of older normal-hearing and -speaking siblings did not seem related to speech and language difficulty. However, when an elder sibling had speech and language difficulty, the younger siblings tended to have similar problems. The relationship between sign and oral language development is ambiguous, but there is no indication that the use of sign language deters oral language development. In view of the high incidence of communication problems in this population, annual audiological evaluations and counseling of deaf parents concerning aspects of hearing loss and normal language development are recommended. The problems encountered in providing therapy are discussed.


Generalization and articulation instruction.

Three young children were taught correct articulation of an error phoneme on a program administered by their mothers in their homes. During the course of the treatment program each child was periodically brought into the speech clinic where the generalization of correct articulation learned in the home treatment setting could be measured in a series of four settings which differed from the treatment setting in varying degrees. Stimulus words which had not been taught during the home articulation program were also included in generalization testing. The results indicated (1) that correct articulation generalized to a high extent to the nontreatment settings investigated; and (2) that responses to new stimulus words were less adequate than responses to words which had received previous training. The clinical implications of these findings are discussed.


Auditory dysfunction accompanying noise-induced hearing loss.

Two groups of 16 young male subjects with normal low- and midfrequency hearing were compared on a series of audiometric measures. One group was composed of subjects with 12- to 24-month histories of noise exposure and hearing loss at 4000 Hz greater than 40 dB; the other group was composed of normal-hearing subjects with no history of unusual noise exposure. On fixed-frequency Bekesy audiometry at 2000 Hz, 12 of the noise-exposed subjects demonstrated separation of 5 dB or more between pulsed- and continuous-tone tracings; similar separation occurred for only one of the non-noise-exposed subjects. Significant between-group differences also occurred on three tests of speech discrimination: PB-50 word lists and CID W-22 lists presented with two forms of competing noise.


Assessment of velar and lateral wall movement by oral telescope and radiographic examination in patients with velopharyngeal inadequacy and in normal subjects.

Thirty-one patients referred to the Craniofacial Anomalies Clinic for speech evaluation were evaluated by endoscopy and cineradiographic examination (lateral and submentovertical projection). Movement of the velar and lateral walls was examined by both procedures in order to determine the accuracy of the endoscopy in assessing velopharyngeal movement. Cineradiography confirmed endoscopic observation in a large percentage of patients. In a second study, lateral wall motion was assessed in 20 cleft palate patients with repaired hard and soft palate but with velopharyngeal inadequacy. Four categories of closure defined in a previous study on normal subjects were used to classify lateral wall movement in the cleft palate patients. Mesial lateral motion past the sides of the velum during phonation occurred less frequently in patients with velopharyngeal inadequacy than in persons with normal strucutres. The absence of lateral wall motion was observed more often in the cleft palate patients, although in over half of these patients the lateral walls moved mesially and filled Rosenmuller's fossa (lateral recesses). Degree of lateral wall movement, which varies among cleft palate patients, should be estimated before construction of a prosthesis or pharyngeal flap in order to determine whether occlusion of the lateral gutters will occur during phonation.


Identification, evaluation, therapy, and follow-up for children with vocal nodules in a public school setting.

This paper describes procedures used by speech and otorhinolaryngology specialists in the Independent School District of Carrollton and Farmers Branch, Texas, to identify, evaluate, treat, and follow up children with voice disorders and presents some initial findings resulting from the use of these procedures. In the identification process, 34 children were found to have vocal nodules, of which 31 children received treatment and underwent appropriate follow-up. After two months of voice therapy, 21 (68%) of the children exhibited reduced nodule size and seven (23%) exhibited normal larynges. Following six months of therapy, 26 (84%) children exhibited reduced nodule size, and 20 (65%) had normal larynges.


Shaping behavior in voice therapy.

This study demonstrates the process of learning and shaping of behavior which occurs during a program of therapy for individuals with hyperfunctional hoarse voice quality. First a therapy program delineating the techniques and criteria to be used was written. The program was presented during 16 individual half-hour sessions over an eight-week period to three clients known to have vocal nodules. The clients' responses were charted at various points from audiotape recordings of each therapy session using a modification of the Boone-Prescott analysis system, to obtain data to demonstrate the learning processes. It was concluded that: (1) the client's behaviors in this vocal rehabilitation program reflected a learning process; (2) facilitating techniques were used to modify or shape behavior through successive approximations to the terminal goal; (3) self-evaluation is an important factor needed to bring about successful changes in behavior; (4) analysis of client's behaviors in relation to the learning process can aid in evaluating the effectiveness of the facilitating techniques; and (5) from such evaluation intraclient and interclient program changes are derived hopefully resulting in a greater success rate and maximum benefits from time spent in therapy.


Progressive lupus glomerulonephritis. Treatment with prednisone and combined prednisone and cyclophosphamide.

We report a prospective randomized study of 39 patients with systemic lupus erythematosus and progressive glomerulonephritis who were assigned to treatment groups that received either prednisone alone or prednisone and cyclophosphamide combined. They received treatment for 6 months and were then followed up for an additional 18 months. No difference in outcome was seen in the two groups at the end of 6 months. Among patients followed up for an average of 24 months, fewer individuals showed later renal progression among those treated with cyclophosphamide and prednisone than among the group treated with prednisone alone.


Hypocomplementemic ear effusion in relapsing polychondritis.

In a case of relapsing polychondritis it was possible to aspirate a collection of subcutaneous fluid from the patient's involved ear. A determination of total hemolytic complement activity of this fluid was low, suggesting that activation of the complement system may have occurred in the course of the patient's disease and might be related to the pathogenesis of this disorder.


Ultrasound evaluation of the popliteal space. Comparison with arthrography and physical examination.

Ultrasound scanning techniques were used to examine the popliteal space in 102 knees. In 30 of 34 knees in which arthrograms were also obtained, the information obtained from both tests was the same. In two instances in which there were different results, the presence of palpable popliteal cysts was confirmed by ultrasound scans but not by arthrography, and in two other cases, small asymptomatic cysts were seen on arthrograms but not on ultrasound scans. In the 68 other knees, ultrasound scans were helpful in the differential diagnosis of popliteal cysts, popliteal artery aneurysms, thrombophlebitis, and a solid poplitieal mass. The results indicate that ultrasound scanning is a valuable, rapid, safe, accurate technique in evaluating patients with symptoms or findings related to the popliteal space.


Skip lesions in temporal arteritis.

Although isolated foci of arteritis ("skip lesions") are presumed to occur in temporal arteritis, there is little documentation of their existence or significance. We have identified skip lesions in 17 of 60 patients (28%) with temporal arteritis, based on a retrospective and prospective examination of temporal artery biopsy specimens. By examining more than 6,000 serial sections of arteries from patients with skip lesions, we have found foci or arteritis as short as 330 mu in length in an otherwise normal biopsy specimen. Our study emphasizes the need to biopsy long segments of artery, to examine multiple histologic sections, and to perform a contralateral temporal artery biopsy when frozen-section examination of the first side is normal.


Joint imaging in polymyalgia rheumatica.

Technetium pertechnetate joint scintigrams were abnormal in 24 of 25 patients with polymyalgia rheumatica, in all 16 with rheumatoid arthritis, in 4 of 13 with nonarticular rheumatism, but in none of 26 control patients. Abnormal uptake in polymyalgia patients was commonest in shoulders and was less likely to be symmetric than in patients with rheumatoid arthritis, in whom distal joint abnormalities predominated. The pattern of abnormal uptake in polymyalgia rheumatica was not different in those with biopsy-proved giant cell arteritis. Correlation between symptoms and abnormal scintigrams was 72%, and abnormal uptake was present in 81% of joints of patients having physical abnormalities. Biopsy showed lymphocytic synovitis in the knee of one patient. After treatment the number of abnormal joints declined. These findings suggest that synovitis is common in polymyalgia rheumatica, and that it may account for some or most of the symptoms in this condition.


Assessment of ambulatory care: application of the tracer methodology.

Utilizing a tracer method in the assessment of care was investigated in a large pediatric clinic. A set of tracers were selected and agreement was obtained concerning the relevance of care criteria by at least 80 per cent of the facility physicians. One tracer, iron-deficiency anemia, was studied using two nonphysician abstractors to review a sample of 100 patient records with hemoglobins of 11.0 gm/100 ml or less. Results were compared with an implicit review by a panel of physicians. In 52 patients, the low hemoglobin level was not recognized. Only 25 patients proceeded through the care levels of evaluation, diagnosis, treatment, and follow-up. Poor compliance was found with the approved criteria. Weighted scores of the explicit tracer method were closely related to ratings by the implicit reviewers. Utilizing tracer assessment with nonphysician abstractors demonstrated remediable deficiencies in health care services.


The staging concept--an approach to the assessment of outcome of ambulatory care.

The paper describes a method to evaluate patient care. The technique is based on the staging concept. Its basic premise is that the seriousness of a patient's condition at some point in the treatment process is a good indicator of the outcome of the previous parts of the process. Data were collected for 5,000 patients who had been admitted to a sample of hospitals in two California cities with a primary diagnosis matching one of the diseases for which staging criteria had been developed. The results indicate that the staging technique can be used to distinguish between the outcomes of ambulatory care received by different population groups.


Quality assurance of ambulatory child health care opinions of practicing physicians about proposed criteria.

This paper reports the opinions of a representative sample of 1,329 physicians providing primary care regarding criteria developed by the Joint Committee on Quality Assurance for evaluation of ambulatory child health care. Areas of care were health supervision (in four age ranges), tonsillopharyngitis, bronchial asthma, and urinary infection. The criteria had been previously appraised by 452 "experts"--academicians and practitioners. Physicians rated criteria for relevance to health outcome, and desirability for use in peer review. They also stated whether they usually performed and recorded each item and gave reasons for not recording. Agreement between the pediatricians and other physicians of the sample and the "experts" was close regarding relevance to health outcome, but many fewer criteria were recommended for peer review by the sample. A significant number of respondents said they performed but did not record many of the criteria. Documentation of only abnormal findings was the main reason given for not recording. Criteria dealing with developmental or behavioral assessment or with counseling were rated lower in all categories than more easily measured items.


The reliability and application of clinical judgment in evaluating the use of hospital beds.

A technique is described which circumvents the difficulty in obtaining reliable judgments by clinicians on cases of inappropriate use of hospital beds. By application of the Delphi method of measuring group expert opinion, convergence was achieved in the estimate, by four physicians, of the total number of bed days wasted on a medical ward during a period of two weeks. Cases of possible misutilization were identified by the author and a second study was designed to measure the effect on the physicans' behavior of her presence on the ward (Hawthorne effect). It is suggested that review of cases of misutilization by the Delphi method could be used in the continuing education of physicians.


The feasibility of an outcome approach to quality assurance--a report from one HMO.

Recent federal legislation has contained the stipulation that participating health maintenance organizations (HMOs) include a quality assurance program which stresses health outcomes. This provision was ostensibly directed at correcting alleged abuses in HMOs serving the urban poor. One version of the outcome method was employed for an 18-month period at an urban HMO caring for 2,000 Medicaid subscribers. The program involved comparing diagnostic accuracy and therapeutic outcomes for clinical conditions relevant to the study population with ideal standards established by the HMO. Three conditions were selected: contraception, depression, and hypertension. The results revealed widespread underdiagnosis (44-74%) in each condition and unacceptable therapeutic outcomes in two. Data collection was hampered by shifts in geography and financial eligibility among the denominator population and low response rates (38-63%) to telephone and mail surveys. Applying the general project guidelines to specific conditions proved considerably more difficult than anticipated. Further refinement of this approach to quality assessment must occur before its widespread use is feasible. Its effectiveness in improving quality remains to be seen. This experience raises doubts regarding the wisdom of legislating a specific outcome approach to quality assessment before feasibility and effectiveness have been demonstrated in organized health settings.


The sickness impact profile: validation of a health status measure.

The Sickness Impact Profile (SIP), a measure of health status, is being developed as an outcome measure of health care. A preliminary study of the validity of the SIP was conducted on a sample of 278 subjects who were grouped into four subsamples differing in kind and severity of sickness. Selfassessment of health status, clinician assessment of health status, and other measures of dysfunction were used as criteria. SIP scores discriminated among subsamples, and correlations between criterion measures and SIP scores provided evidence for the validity of the SIP. Differences among the correlations obtained for each criterion measure with SIP score are discussed in terms of the need for the development of criterion measures that can be expected to differentially relate to the constructs inherent in the SIP.


A strategy for redesigning the medical record for quality assurance.

The medical record should be viewed as an instrument to facilitate and demonstrate the achievement of explicit health care goals. Current systems do not accomplish this. Our examination of the traditional record suggests that modifications of the record should be based on the principles of information system design theory. Necessary modifications include changes which prompt the monitoring of the outcome parameters of a patient's illness, encourage the analysis of the patient's outcome, and facilitate adaptive (corrective) actions. We have termed those data elements which describe the achievement of patient-specific, problem-specific objectives as the "minimum care assurance data set." To designers of computerized medical information systems, this approach provides a rationale for selecting which data to place in computer storage from the myriad of detail in the traditional paper record.


Adenomatous tumors of the middle ear and mastoid.

Three cases of middle ear and mastoid neoplasms are reported as "adenomatous tumors" since in their search of the literature the authors did not find any previously described lesions with a similar histologic appearance and benign biologic behavior. Microscopically, all three tumors are similarly composed of solid cords and nests of closely-packed small cells having an epithelial appearance. Two distinct cell types are present: cuboidal cells, arranged in a rudimentary gland-like pattern, and angular cells forming irregular nests with no distinct pattern. All three tumors developed in patients in their 20's, over a period of months with minimal symptoms; yet in all of the lesions the tympanic membrane was intact at the time of initial examination. None of the neoplasms was diagnosed preoperatively, and, once removed, all three tumors were pathologic enigmas and therapeutic problems in view of the initial and subsequent consultant pathologic opinions; nevertheless, total local excision with preservation of the tympanic membrane would appear to be safe treatment in these cases. The term "adenomatous tumor" is applied to these three neoplasms because: 1. a true glandular epithelial origin warranting the term adenoma or adenocarcinoma cannot be proven; and 2. the biologic behavior and prognosis is not necessarily reflected by the histologic appearance. A more specific term reflecting the origin and behavior of these tumors does not appear possible without the study of further cases.


Metastatic disease of the temporal bone.

This paper discusses metastatic disease of the temporal bone, and illustrates its discussion with a case history. The incidence, signs, symptoms, and treatment generally recorded are discussed. The histopathology of such lesions, as well as a documentation of those organ systems most likely to provide temporal bone metastatic spread, is noted. As the primary neoplasias of the temporal bone, metastatic disease may coexist with or mimic chronic otitis media. It is the wary surgeon who carefully analyzed his patient, the history, the intensity of recognizing neoplasia with or without associated chronic otitis media.


Meningiomas of the temporal bone.

Meningiomas should be considered in the differential diagnosis of otologic tumors arising from the middle ear and mastoid. It is generally recognized that meningiomas may invade the temporal bone via direct extension from the intracranial space (secondary). It is not generally recognized that meningiomas can develop initially in the middle ear cleft (primary). Representative cases of primary and secondary meningiomas of the temporal bone are described and clinical aspects of diagnosis surgical management are discussed. In order to assess the pathogenesis of meningiomas of the temporal bone, histological studies were done on 200 temporal bone specimens. In certain specimens, ectopic arachnoid granulations, from which primary meningiomas may originate, were identified and described, according to location. One specimen was most unusual in that it contained ectopic glial as well as arachnoidal tissue.


Malignancies of the ear.

Cancer of the ear is an uncommon occurrence and rarely diagnosed early it its development. Routine biopsy of all granulomatous and neoplastic diseases of the ear is essential to early diagnosis. Polytomography is an aid in documenting the extent of the disease in bone. The surgical anatomy of the region of the ear imposes special disadvantages upon any type of surgical technique employed and supervoltage irradiation given. Temporal bone resection and its modifications, combined with irradiation, enhance the cure rate in the advanced cases and add significantly to the local control of this disease. A review of 273 cases is presented.


The human external auditory canal, secretory system--an ultrastructural study.

Human external auditory canal skin, with a special emphasis on the secretory system, was studied by light, transmission electron and scanning electron microscopy. Two types of secretory glands were observed: modified apocrine (ceruminous) and sebaceous. The sebaceous secretory cellere homogeneous; on the other hand, modified apocrine secretory cells contained heterogeneous secretory granules. They were ither dark granules or light granules. Evidence to support both the apocrine as well as the eccrine mode of secretion was noted in the modified apocrine gland. This finding is partly in agreement with early reports based on light microscopy with suggested only an apocrine mode and data based on transmission electron microscopy which showed only the eccrine mode. Significance of the secretion by the external ear canal and its role in a local immune defense system is discussed.


The use of homograft stapes.

Homograft stapes were used for ossicular reconstruction in 43 ears over a three-year period. The average hearing improvement was 7.9 db. These cases were divided into groups: those with an intact posterior canal wall and those with an open mastoid cavity. The latter group fared better, with an average improvement of 15 db. Fourteen of the 43 ears were subsequently re-explored. Satisfactory bony union between the homograft stapes and recipient footplate was found in eight cases, four cases showed poor bony union, and bony resorption of the homograft had occurred in two patiemise for reconstruction of the ear with a loss of the stapes arch, especially in the presence of an open mastoid cavity and thus a shallow middle ear.


Epitympanic malleus fixation: correction without disrupting the ossicular chain.

The preoperative diagnosis of malleus fixation can be made consistently with a pneumatic otoscope. Nontympanosclerotic epitympanic malleus fixation, for the most part, has been corrected by disrupting the ossicular chain and then reconstructing the sound-conducting mechanism. Once the diagnosis of malleus fixation is established, the surgical approach should be modified to cope with the fixed malleus. A wide, inferiorly based tympanotomy flap affords ample access to the epitympanum and permits definitive resolution of the associated conductive hearing loss. Atticotomy and discreet osteotomy can free the fixed malleus and preserve continuity of the osscular chain in over 90 percent of the patients with this syndrome. Experience for 46 patients having bony epitympanic malleus fixation, both congenital and acquired, was examined in concluding that the anatomical continuity of the ossicular chain can and should be maintained in most patients. The residual air-bone gap is less with an intact, though modified, ossicular chain than it is with a chain that has been reconstructed.


The role of aminopeptidases in inflammatory and neoplastic tissues.

The role of leucine andalanine aminopeptidases is stidued in three different biologic systems: experimental wound healing in the rat, experimental carrageenan induced intraderman granulomas in the rat, and human laryngeal carcinomas. The wound healing experiments indicate that the proliferating granulation tissue has high quantities of aminopeptidases activity which is residing primarily intracellularly in granulocytes, macrophages, mast cells fibroblasts, and new budding vessels. The quantititave levels of tissue aminopeptidases correlate positively with the degree of cellularity of the wound and fibroblastic activity. Some aminopeptidases (isoenzymes) are secreted or released by the fibroblasts in be blood serum. Starch gel electrophoretic analysis demonstrates thses with different concentrations and migration rates. Two are probably released or secreted into the serum, and th third is membranous bound in the cytoplasm (lysosomal). The carrageenan intradermal granuloma demonstrates a different inflammatory reaction which is rich in macrophages and produces a different pattern of aminopeptidases activity. Macrophages produce a high tissue level of aminopeptidase activity which is intracellular bound and not readily leached out into the serum. Gel electrophoresis studies of aminopeptidases produced by the granuloma demonstrate that the tissue bound enzyme is the main component. In addition, there appears to be a mechanism, which is not understood, for specific induction or activation of lysosomal proteolytic and carbohydrase enzymes. This mechanism is dependent on the nature of composition of the injuring agent. Laryngeal carcinomas demonstrate high tissue homogenate levels and normal serum levels of aminopeptidase activities. These enzymes are located in the tumor stroma. They are not directly related to tumor invasiveness but to the degree of stromal proliferation. The tumor stroma behaves as though it were a non-healing wound constantly secreted proteolytic enzymes (aminopeptidases). A major problem that needs to be resolved is to find the operating mechanism by which malignant cells interact with their constantly proliferating fibroblastic stroma.


Isolated laryngeal lymphoma.

Isolated laryngeal lymphoma is a rare occurrence. We found a total of 14 previously reported cases. These plus ouradditional case are reviewed in order to make recommendations for diagnosis, therapy,a nd follow-up. Histologic classification and clinical staging of lymphomas have limited usefulness, because the tumor can change cell type during the clinical course of the disease. Once histologic proof of the tumor exists, adequate evaluation consists of physical examination to detect adenopathy elsewhere, bone marrow biopsy, urinalysis, blood uric acid levels, liver biopsy, and liver and kidney function tests. The search must continue in the chest by X-ray, the retroperitoneal nodes by lymphangiography and the abdomonal visera by contrast radiography. Radiation therapy is the best initial treatment for isolated laryngeal lymphoma. If the tumor does not respond to irradiation, then operation to remove the lesion is required. This tumor has a tendency to recur at distant sites many years later. As with all cancer patients life-long follow-up is required.


Cervical hibernoma.

The hibernoma is a rare neoplasm derived from vestigal remnants of brown fat left from early embryologic development. Review of the world literature reveals only 40 cases to which we are adding a report of a tumor arising in the posterior cervical triangle of a 20-year-old man. The distribution, histology and cytochemistry of brown fat and the hibernoma are discussed, and evidence supporting its histogensis is presented.


Observations on the biochemical effects of transfusion of citrate-phosphate-dextrose stored blood in man.

Preliminary data on the biochemical effects of the transfusion of three units of CPD blood in man is presented. Free (ionized) calcium was found to decrease approximately two minutes following initiation of the transfusion of CPD stored blood at a rate of 50 ml/min. Due to mixing problems, arterial and not venous specimens were found necessary to monitor accurately the severity of these decreases. Parathyroid hormone in the peripheral blood was found to increase two to four minutes after the initiation of transfusion. Decreases in blood pressure were observed during transfusion. The blood pressure recovered when the transfusion was stopped and did not decrease any further after restarting the transfusion, were found out not to increase or decrease consistently, and only modest changes in plasma potassium were observed.


Management of phenylketonuria: South Australian experience of 13 cases.

The management and present status of 13 children with phenylketonuria detected on the fifth day of life, who have been treated by diet thereafter for five to eight years, are discussed. In all 10 cases in which there has been continuous adequate dietary control of blood phenylalanine levels, the physical, social and mental development of the children has been normal. In some of these cases there is an unexplained discrepancy between the verbal and performance IQ scores. The present policy is to continue restricting the diet indefinitely, relaxation being permitted conditionally only after the age of seven years.


Painful ophthalmoplegia following treated squamous carcinoma of the forehead. Orbital apex involvement from centripetal spread via the supraorbital nerve.

Intraneural and perineural spread of squamous carcinoma from the face to the cranial cavity is an important cause of delayed cranial nerve palsies after local excision of a skin tumour. As exemplified in reports of two cases, signs of this type of centripetal spread of squamous cell tumour along the branches and trunk of the supraorbital nerve are (i) severe unremitting orbital and forehead pain with associated hypoaesthesia, (ii) palpable or radiological evidence of thickening of the nerve at the supraorbital notch and (iii) evolution of ophthalmoplegia, blindness, and sensory loss in the first division of the trigeminal nerve. Appearance of severe supraorbital neuralgia months or years after excision of a skin tumour from the forehead should alert the clinician to extension of tumour cells along the supraorbital nerve. This may enable him to institute timely treatment before a complete orbital apex syndrome has developed.


Vesico-ureteric reflux.

There is increasing awareness that vesico-ureteric reflux is associated with the occurrence of renal scars. The influence of infection in scar formation is unclear. The way in which corrective surgery may prevent scar development in selected patients is gradually becoming apparent. It would seem probable that surgical correction of vesico-ureteric reflux is indicated only in infants and young children with gross vesico-ureteric reflux.


Social work and general practice: a review article.

Closer collaboration with social workers may be a means of enabling the general practitioner to deal with the psychosocial problems expressed in his practice. Emerging interest on the part of general practitioners in exploring the potential contribution of the social worker to patient care is accompanied by some anxiety and ambivalence. Reports of collaborative projects have come mainly from the United Kingdom, and although these offer some guidelines, it is imperative that any policy proposals for the development of closer general practitioner-social worker collaboration in Australia be grounded in an Australian data base.


General practice and professional coordination.

In a satellite city in South Australia, 17 miles from Adelaide, a controlled experiment in which a social worker from a local community agency has been placed in a four-man practice is demonstrating one way in which new forms of professional coordination can evolve out of already existing services. Through daily face-to-face contact, doctors, and social worker, as well as other surgery staff members, are learning ways of cooperating in unravelling the many mixed medical and psychosocial problems that present in a general practice setting. There are indications that community response to the innovation is positive because the doctors develop an assurance in making referrals, and people see the service as an extension of a known service in an already familiar setting.


The general practice and social work. Report on a trial.

This report describes the experience of a social work student placement of 10 weeks' duration in a two-man general practice in Perth, Western Australia. The student was completing the final year of the degree of Master of Social Work at the University of Western Australia, and this was the student's third and final practical assignment. In particular, the report describes the means of referral, the nature and size of the social work service on the doctor-patient relationship.


[Alteration of coronary blood flow after injection of a contrast medium (author's transl)].

The injection of with different, energetic separable radioactive isotope labelled particles in the same coronary artery before and short after the injection of a contrast medium reveals in many cases variable scintigraphic pictures. The temporary vasodilatation caused by the contrast medium produces in presence of a coronary stenosis a disturbance of the regional blood flow. Thereby we find in the poststenotic myocardial area a transient ischemia, bringing about a decrease of the activity at the scintigram. As this transient ischemia is only demonstrable with a hemodynamic effective stenosis, in such cases a good effect of coronary surgery can be expected. On the other hand, in the presence of effective stenoses in all three coronary branches, in the double-scintigram alterations of the perfusion can be missed, showing the same scintigraphic picture as with normal coronary arteries.


[Mendelson's syndrome in coronary care units (author's transl)].

By means of the case of a patient resuscitated after cardiac arrest attention is brought to the occurring of Mendelson's syndrome in coronary care units. Aspiration pneumonitis following inhalation of acid gastric contents is little known outside of anesthesia, but is likely to occur more frequent than its diagnosis is made. A considerable black number is to be expected, mostly because of the danger that the aspiration itself has not been registered and the pulmonary edema setting in after a latency of several hours is regarded as sequela of the underlying heart disease. But this misunderstanding can have deleterious effects, because therapy has to consider a hypovolemia caused by the fluid loss into the lungs. Therefore pathogenesis and therapy of the lung edema in Mendelson's syndrome are carefully delineated. In patients surviving the acute stage of the disease, further prognosis is favorable: late sequelae have so far not been observed.


Metabolism of caffeine to nucleic acid precursors in mammalian cells.

Caffeine is rapidly metabolized in human and mouse cells in culture by de-methylation: within 1-3 h of exposure to millimolar concentrations of labeled caffeine, more than 90% of the pool consists of labeled products of metabolism and less than 10% is still caffeine. The methyl groups seem to be transferred and used in the de novo synthesis of thymine, guanine, and adenine to nucleic acids. Normal fibroblasts, Lesch-Nyhan fibroblasts, xeroderma pigmentosum fibroblasts, HeLa cells, wild type mouse cells, and adenine phosphoribosyl-transferase-deficient mouse cells all seem to metabolize caffeine similarly.


The isolation and preliminary characterisation of 6-thioguanine-resistant mutants of human diploid fibroblasts.

Mutant clones of human diploid fibroblasts deficient in the enzyme, hypoxanthine-guanine phosphoribosyl transferase (HGPRT) were selected by their ability to grow in medium containing the cytotoxic purine analogue, 6-thioguanine (6TG). The optimal condtions for mutant selection were 6TG concentrations between 1 and 5 mug ml1 and cell plating densities approximately 10(3) cells cm-2. Nine spontaneous and four radiation-induced 6TG-resistant mutants had less than 2% of the parental strain HGPRT activity and were unable to grow in medium containing azaserine. These mutants were phenotypically stable during greater than 25 population doublings in non-selective medium and five mutants that were examined showed no gross change from the normal human karyotype. Evidence is presented to show that 6TG is a better selective agent than 8-aza-guanine (8AG) for HGPRT-deficient mutants of human diploid fibroblasts.


Radiation-induced DNA scissions and their rejoining in testicular cells of mouse.

The radiosensitivity of DNA molecules in testicular cells from adult male mice in situ was 0.22 single-strand breks per 10(12) daltons of DNA per rad. This was significantly lower than the 0.6-0.7 for liver and thymus DNA, and was most likely attributable to a hypoxic condition of testicular cells in situ. Although a majority of the single-strand scissions was quickly rejoined, a significant extent of breaks remained without further rejoining. The presence of remaining breaks was demonstrated not only after 3-6 h of post-irradiation time, but also after irradiation at low dose rates. The remaining breaks might be a slow and/or non-reparable DNA damage.


Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis.

Four patients with chronic hepatitis B infection and chronic active hepatitis were treated with human leukocyte interferon. Three of them had consistently elevated levels of circulating Dane-particle markers, including Dane-particle-associated DNA polymerase activity, hepatitis B core antigen and Dane-particle-associated DNA. Parenteral interferon administration at a dosage between 6.0 X 10(3) and 17 X 10(4) U per kilogram per day was associated with a rapid and reproducible fall in all Dane-particle markers in the three patients. The suppressive effect was transient when the interferon was given for 10 days or less but appeared to be more permanent when administration was prolonged for a month or more. In addition, long-term interferon therapy was associated with a marked fall in hepatitis B surface antigen in two of three patients and a disappearance of e antigen in two of two patients. Interferon may be useful in limiting carrier infectivity or eradicating chronic infection.