Fibrous xanthoma of the frontal sinus.

Frontal sinus mucocele was our preoperative diagnosis in a patient who had frontal swelling and downward displacement of the eye. Supporting this were typical roentgenogram changes, a long history of asthma, pansinusitis, and previous multiple-polypectomy surgery. Frontal sinus exploration revealed a locally eroding lesion. It was composed of spindled cells and lipid-laden histiocytes with a pattern of fibrous xanthoma and was treated conservatively. It should not be confused with true malignancies such as fibrous histiocytoma having a similar histopathologic appearance and requiring more aggressive surgical treatment.


Lentigo maligna melanoma.

Lentigo maligna melanoma is a malignant melanoma with a recognizable clinical pattern. It is a slow-growing, pigmented tumor evolving from a premalignant lesion on the exposed cutaneous surface of an elderly patient. Histologically, it is marked by pleomorphism of melanocytes with evidence of invasion. A case is presented demonstrating the features of this malignant melanoma with an exceptionally good prognosis. The importance of the clinical and histologic correlation of emphasized to ensure proper diagnosis and treatment.


Rabies: otolaryngologic manifestations.

Rabies is a rare, fatal viral infection, usually transmitted by the bite of an infected animal. Some 30,000 Americans are immunized annually, however, so public health considerations are common. The development of a new vaccine, grown in human diploid cell culture, is discussed. It appears to have high antigenicity with no serious morbidity. A case of a patient with fatal rabies who had fever, delirium, dysphagia, and cervical and pectoral subcutaneous emphysema is presented.


Bronchogenic cysts: a case report.

The otolaryngologist has a reference frame for congenital stridor that rarely includes diagnosis of a bronchogenic cyst. The life-threatening potential of this lesion makes consideration and recognition imperative. Representing less than 5% of the mediastinal childhood masses in the infant, respiratory distress most often initiates diagnostic studies leading to identification and extirpation. The case presentation highlights the clinical course. The diagnostic hallmark of this case was the delayed onset of stridor with subsequent progression. Thereafter, a chest film and barium swallow suggested the diagnosis. In newborns, however, such cysts may not be evident on routine chest films and, nonetheless, cause significant respiratory distress from airway compression. Surgical extirpation should be affected as soon as possible after the diagnosis is entertained in order to insure against a sudden respiratory death.


Adult invasive subcutaneous hemangioma.

Hemangiomas consist of a spectrum of benign vascular tumors with variable clinical behavior and microscopic morphology, which usually occur in infancy. A rare variant of these tumors is the invasive subcutaneous hemangioma, which shows an aggressive growth pattern by invading subcutaneous structures and recurring after apparent excision. The authors describe an adult patient with a large submandibular invasive hemangioma who was treated by preoperative embolization and surgical excision.


Surgery of the skull base: transcochlear approach to the petrous apex and clivus.

The transcochlear approach is described for resection of lesions arising anterior or medial to the internal auditory canal as well as for those arising directly from the clivus. Through an extended complete mastoidectomy the facial nerve is totally decompressed and re-routed posteriorly from the stylomastoid foramen to the internal auditory canal. The fallopian canal, promontorium, and cochlea are removed anteriorly and medially as far as the internal carotid artery, obtaining exposure to a triangular area limited by the superior petrosal sinus, inferior petrosal sinus, carotid, and internal auditory canal, giving adequate exposure to the structures of the clivus and the midline (basilar artery, vertebral arteries, and the sixth cranial nerves).


Biofeedback training and relaxation exercises for treatment of temporomandibular joint dysfunction.

Biofeedback training involves electromyographic recording of the patient's level of facial muscle tension with concurrent presentation of that level to the patient in a visual or auditory manner. The objective of biofeedback training in patients with temporomandibular joint dysfunction is to provide them with an insight into abnormal facial muscle activities, which include clenching and grinding of the teeth and lip- and cheek-biting habits. This insight coupled with relaxation programs affords the patient an opportunity to eliminate abnormal behavior patterns that foster temporomandibular joint symptomatology.


Cis-platinum chemotherapy in head and neck cancers.

Sixteen patients with advanced head and neck carcinomas were treated with cis-diaminedichloro platinum chemotherapy; seven preoperatively and nine for recurrent disease. Cis-platinum was given by 24-hour infusions of 80 mg/m2 every three weeks. There was 50% regression in 38% (6) of the patients; another 38% (6) had 25% to 50% regression. Toxicity was minimal, with vomiting occurring in 75% (12) of the courses, renal toxicity in 6% (2), leukopenia in 13% (4), thrombocytopenia in 9% (3), and anemia in 31% (10). Of the seven patients who had serial audiograms, only one experienced ototoxicity. Cis-platinum, given by 24-hour infusion, was effective in reducing tumor bulk in 75% (12) of the patients, with advanced head and neck carcinomas, without undue morbidity.


Aspergillus thyroiditis.

A case of fatal disseminated aspergillosis in a renal transplant patient is presented. The initial manifestation of the disease was consistent with thyroiditis. Autopsy findings are shown and support this unique presentation. The diagnosis of aspergillosis is difficult to make and may require pulmonary biopsy. Early diagnosis and treatment with amphotericin B are the keys to successful management of the disease.


Fibroblast implantation enhances wound healing as indicated by breaking strength determinations.

Irradiation of normal tissues at the dose/time factor employed in the treatment of solid tumors impairs the subsequent healing of surgical wounds made in those tissues. Irreversible radiation damage to regional fibroblasts is one cause of impaired healing. This study was conducted to determine whether syngeneic guinea pig fibroblasts, harvested from tissue culture when injected into irradiated guinea pig skin at the time of wound closure, could improve wound healing. Breaking strength determinations indicate that irradiated wounds demonstrate enhanced wound healing if implanted with fibroblasts.


Contralaterally elicited electrical stimulation of paralyzed facial muscles.

Functional electrical stimulation is being explored in the extremities. A major obstacle is found in programming the firing sequence. In 1976, David Zealear proposed using the activity on the normal side in axial muscle pairs that normally function symmetrically to act as a template to control the stimulator. This method was demonstrated in laryngeal muscles in dogs, and is now demonstrated in the face with future applications being proposed. The facial nerve on one side was sectioned in a series of rabbits. Implanted electrodes received electrical potentials from selected muscles on the normal side. Bursts of electrical activity on the normal side during a blink or a twitch were used to trigger a muscle stimulator, which was routed to matching muscles on the paralyzed side. This technique restored symmetric function to the hemiparalyzed side. This technique restored symmetric function to the hemiparalyzed face.


High-frequency hearing losses caused by low-frequency noises.

Human subjects were exposed to an octave-band noise for 24 hours. Temporary threshold shifts increased for the first eight hours of exposure and then were asymptotic. While threshold shifts were largest at about one-half octave above the center frequency of the noise, a second maximum was observed at higher test frequencies. The exact frequency of this second maximum decreased from 7.0 kHz, for a noise centered at 2.0 kHz, to 5.5 kHz for a noise centered at 0.5 kHz. This result could be caused by the travelling wave pattern along the cochlear partition or to the production of distortion products.


Sources of error in interpretation of caloric tests.

Caloric testing plays a prominent role in evaluating the vestibular system. A unilateral reduced vestibular response (RVR) is a common abnormality and is consistent with peripheral vestibular pathology. An erroneous interpretation of RVR may be made due to the following circumstances: laboratory technique, the influence of directional preponderance (DP) on monothermal tests (MT), unilateral hyperactivity, or pseudocaloric (PC) nystagmus. These errors in interpretation may be avoided by (1) repeating any single irrigation that is significantly different from the other three, to rule out laboratory technical error; (2) performing bithermal (BT) testing exists, to eliminate the effects of directional preponderance; (3) observing that a right/left (R/L) difference is not due to unilateral hyperactivity, by noting absolute slow phase (SP) velocity; and (4) by demonstrating bidirectional sensitivity of the cupula before concluding that residual caloric function exists instead of no function.


Nutritional problems in developing countries.

Nutritional problems in children constitute the major health problem in developing countries. Impact of a factors leading to different kinds of nutritional problems in developing countries are reviewed. Prevention and treatment of some special disease states are discussed. Outlines for some solutions to the greatest nutritional problems are presented.


Experimental arteriosclerosis in Rhesus monkeys induced by multiple risk factors: cholesterol, vitamin D, and nictotine.

Forty-four rhesus monkeys were given various regimens involving three vasotoxic factors: dietary hypercholesteremia, hypervitaminosis D2 and nicotinism for period ranging from 14 to 62 weeks. When administered singly, no or only early disease was observed. The combined three "risk factor" group demonstrated the most impressive arteriosclerosis. Major arteriosclerotic changes: fat, calcium and mensenchyme of thirty standardized segments of aorta, coronary and limb arteries of all monkeys were graded according to a standardized system. Statistical analysis revealed that the total arteriosclerotic scores of the three vasotoxic factor group was significantly greater than those of any other group and that this was the only group with significant coronary arteriosclerosis as well as complicated lesions such as thrombosis or occlusion of arterial luminae of the extremities. A lowering of the vitamin D2 dosage, resulting in a lengthening of the survival time of animals which should allow sufficient time for complicated disease to develop, is recommended for future studies.


The eustachian tube prosthesis revisited.

Preliminary results with an eustachian tube prosthesis have been reported. This paper updates our experience with the prosthesis. Our series is now 95 patients with follow-up of 2 to 32 months (average of 14 months). The success rate in obtaining a healed aerated middle ear is 75% (71). The eustachian tube prosthesis continues to give encouraging results in problem tympanoplasty cases.


Measles virus induced lectin binding in cultured, aortic cells.

Using the indirect hemadsorption test it was shown that cultured diploid cells of mini-pig, monkey or human aortic origin develop wheat germ lectin/WGA/binding capacity following infection with measles virus. Heteroploid cell lines of similar origin have bound WGA also without being infected with virus. The possible role of virus induced membrane changes in vascular cell pathology is suggested by the results presented.


Pancreatitis associated with valproic acid therapy.

The development of acute pancreatitis in an 8-year-old boy being treated with valproic acid for simple absence spells is documented. A brief discussion of the other previously reported complications with valproic acid is included.


Polychlorinated biphenyls and other organic chemical residues in fish from major watersheds of the United States, 1976.

Composite samples of fish were collected from major United States watersheds in 1976 and analyzed for PCBs and related organic chemicals. PCBs were found in 93 percent of the fish samples; 53 percent of the samples contained more than 5 ppm PCBs, whole fish basis, which is the current tolerance level set by the Food and Drug Administration, U.S. Department of Health, Education and Welfare. Only 14 percent of the samples contained less than the proposed action level of 2 ppm PCBs. PCB concentrations ranged from less than 0.3 ppm to 140 ppm in the composite samples. sigma DDT concentrations ranged from less than 0.05 ppm to 4.53 ppm. Hexachlorobenzene was identified in 19 percent of the samples, and chlordane components were identified in 36 percent of the samples. Chemicals identified by gas chromatography/mass spectrometry but not quantified include chlorinated benzenes, styrenes, anisoles, phenols, anilines, propanes, and butadienes, as well as mixtures of petroleum hydrocarbons.


Nationwide residues of organochlorine compounds in wings of adult mallards and black ducks, 1976-77.

Organochlorine residues in wings of adult mallards and black ducks were monitored nationwide during the 1976-77 hunting season. DDE was found in all samples. Levels were unchanged since the 1972-73 collections in all migratory routes except the Pacific Flyway, in which residue levels declined significantly. Dieldrin levels had not changed in any flyway and residues remained low. PCB levels declined significantly in the Atlantic Flyway but remained stable in other flyways. Heptachlor epoxide, mirex, endrin, hexachlorobenzene, and chlordane isomers were detected in low amounts in some samples.


Organochlorine residues in fish, water, and sediment of American Falls Reservoir, Idaho, 1974.

Organochlorine residues of TDE, DDE, and PCBs as high as 1.96, 2.79, and 28.74 microgram/kg, respectively, have been found in sediments of American Falls Reservoir, Idaho. Residues of TDE, DDE, and dieldrin in the flesh of sport fish were as high as 52.3, 67.2, and 160.4 microgram/kg, respectively. Maximum organochlorine residue levels found in sucker taken in the commercial fishery were 1.1 mg PCBs/kg, 781.7 microgram TDE/kg, and 82.1 microgram DDE/kg.


[Glutaraldehyde test on whole blood of swine at slaughter--a preliminary report].

In an initial experiment the highest concentration of a glutaraldehyde solution that does not coagulate whole blood of fatteners without or with only slight pathological changes was established. Total protein, albumin, globulin, A/G ratio and electrophoretic protein pattern were at the same time determined in blood serum. A glutaraldehyde solution with the established highest concentration was used in a second experiment on whole blood to distinguish fatteners without or with only small pathological changes from those with severe processes such as abscesses and purulent arthritis. It is evident that the glutaraldehyde test gives a good idea of the immunoglobulin status of fatteners. There is reason to believe that systematized glutaraldehyde testing of whole blood taken at pig slaughter could improve the chances of detecting concealed inflammatory processes.


[Combined test for assessment of anterior pituitary function using glucagon-propranolol, TRH and LHRH (author's transl)].

Combined Glucagon-Propranolol test used for study of growth hormone is advantages. The combined administration of TRH and LHRH is possible. In 53 children, the hormone responses (GH, TSH, FSH, LH and prolactin) were studied. This combined test allows the rapid assessment of anterior pituitary function.


[The venous route in total parenteral nutrition of the adult patient (author's transl)].

Total parenteral nutrition (T.P.N.) takes presently an important place in the therapeutic methods. Nevertheless multiple complications, directly related to the venous route can constitute a limiting factor in the application of such procedures. Therefore complications such as sepsis and venous thrombosis must be prevented during T.P.N. Some conditions issued from our experiences and from the results in the literature can be now well defined: 1) Surgical catheterization of the vein in cases of long term T.P.N. and transcutaneously in cases of short term T.P.N. with in all cases a long subcutaneous way of the catheter. 2) Silastic catheter must be systematically used. 3) The intravenous way of the catheter must be as short as possible. 4) Nutrients must be strictly infused in the superior vena cava. 5) The utilisation of nutritive mixtures must be prefered if possible. 6) Handling of the infusion line must be avoided. Finally the management of T.P.N. in the best conditions requires a specialized staff.


[Pharmacokinetic perturbations in kidney failure. Anomalies of metabolites and tissue diffusion (author's transl)].

Complex pharmacokinetic perturbations follow kidney failure. Delayed excretion affects not only the original substance but also metabolites, as illustrated by the behaviour of glipizide and glibenclamide. Moreover, abnormal absorption, distribution, and metabolism of these drugs also often occur and are particularily evident for some beta-blocking agents. Analysis of tissue pharmacokinetics shows that aminosides accumulate in the renal cortexand persist there for several months. This phenomenon is markedly enhanced in acute obstructive kidney failure and largely accounts for the nephrotoxicity of these drugs.


Biological activity of the intact and cleaved DNA of the simian adenovirus 7.

Only the deproteinized DNA preparations of the simian adenovirus of the type 7 (SA 7) exhibited transforming and tumorigenic activity. The complex of the SA7 DNA with terminal protein (TP) did not exhibit either transforming or tumorigenic activity in cell cultures. In contrast to the transforming potential the infectious titers of the DNA - TP complex for the monkey kidney cells were 30-50 times higher than those of pure DNA. Cleavage of the SA7 DNA by specific endonucleases enhanced the tumorigenic potential of pure DNA, suppressed its infectivity and did not affect the lack of transformation capacity of the DNA - TP complex. The onc-gene was localized in the left terminal fragment with the minimal size 4,3x10(6)D in the case of R.Sal I. The tumorigenic activity was found to decrease with an increase in the size of the DNA fragment containing the onc-gene.


Subunit structure of alpha-satellite DNA containing chromatin from African green monkey cells.

alpha-Satellite DNA containing chromatin from African green monkey cells (CV-1 cells) has been used to study the question whether or not nucleosomes are arranged in phase with the 172 bp repeat unit of the satellite DNA. Digestion experiments with DNAase II led us to exclude a simple phase relationship between the nucleosomal and the satellite DNA repeats. Digestion of CV-1 nuclei with micrococcal nuclease and endogenous nuclease (s) produced a series of sharp bands in the satellite DNA register over a background of heterogeneous length fragments. This observation is explained by a preferential cleavage of certain nucleotide sequences by these nucleases and is not in contradiction to our conclusion that a simple phase relationship does not exist.


Comparison of the A-T rich regions and the Bacillus subtilis RNA polymerase binding sites in phage phi 29 DNA.

By using a modification of the BAC spreading method for mounting the DNA for electron microscopy, partial denaturation maps of protein-free phi 29 DNA and of phi 29 DNA containing protein p3 were obtained. In phi 29 p3-DNA1 the protein does not seem to influence the melting of the ends of the molecules. The comparison of the partial denaturation map and the B. subtilis RNA polymerase binding sites indicates that five of the seven early promoters (A1, A2, A3, B2 and C2) are located in A-T rich DNA regions whereas the other two early promoters (B1 and C1) are located in less A-T rich sites.


Pseudouridylation of yeast ribosomal precursor RNA.

The pseudouridylation of ribosomal RNA of Saccharomyces carlsbergensis was investigated with respect to its timing during the maturation of rRNA and its sequence specificity. Analysis of 37-S RNA, the common precursor to 17-S, 5.8-S and 26-S rRNA and most probably the primary ribosomal transcript, shows that this RNA molecule contains already most if not all of the 36-37 pseudouridine residues found in the mature rRNAs. Thus pseudouridylation is, like 2'-0-ribosemethylation, an early event in the maturation of rRNA, taking place immediately after, or even during, transcription. The data presented show that the non-conserved sequences of 37-S precursor rRNA contain very few pseudouridine residues if any. The pseudouridine residues within the rRNA sequences are apparently clustered to a certain degree as can inferred from the occurrence of a single oligonucleotide containing 3 pseudouridines, which was obtained by digestion of 26-S rRNA with ribonuclease T1.


Formation of ribosome-RNA initiation complexes with alfalfa mosaic virus RNA 4 and RNA 3.

RNA 4 of alfalfa mosaic virus (AMV) is a monocistronic messenger for the coat protein. We have determined the sequence of the 40 +/- 2 nucleotides in RNA 4 that were protected in the initiation complex formed with wheat germ 80 S ribosomes from digestion by T1 or pancreatic ribonucleases. The AUG coat protein initiation codon was near the middle of this protected region. We have found two ribosome-binding sites in RNA 3. The principal one, near the 5' end, is the initiation site for the major translation product, a 35,000 dalton protein. The second site binds ribosomes only weakly, at the beginning of the "silent" coat protein cistron, and is similar but not identical to the initiation site protection site is discussed.


PaeExo IX: a unique deoxyribonuclease from Pseudomonas aeruginosa active in the presence of EDTA.

A new deoxyribonuclease, PaeExo IX, has been purified to electrophoretic homogeneity from extracts of Pseudomonas aeruginosa strain PAO. This enzyme, which is active in the presence of EDTA, is equally efficient in hydrolyzing native and heart-denatured DNA to acid-s-luble products. The enzyme is partially or totally inhibited by the presence of several divalent cations. The active protein has a molecular weight of 1.6 +/- 0.1 x 10(5) and is composed of two nonidentical polypeptides with molecular weights of 78,000 and 69,000.


Restriction analysis of spacers in ribosomal DNA of Drosophila melanogaster.

The sequence arrangement of ribosomal DNA (rDNA) spacers in Drosophila melanogaster was analyzed with restriction endonucleases. Spacers, derived from cloned rDNA repeats and from uncloned purified rDNA, are internally repetitive, as demonstrated by the regular 250 base pairs interval between sites recognized by the enzyme Alu I. Length heterogeneity of spacers is due at least in part to varying numbers of repeated sequence elements. All spacers and analyzed, whether derived from X or from Y chromosomal rDNA, have a very similar sequence organization. The distance separating the repeated nontranscribed spacer sequences from the 5' end of the transcribed region is conserved in all ten cloned fragments examined, and is probably less than 150 base pairs, as measured by electron microscopy.


The nucleotide sequence of phenylalanine tRNA2 of Drosophila melanogaster: four isoacceptors with one basic sequence.

The nucleotide sequence of Drosophila melanogaster phenylalanine tRNA2 was determined to be: pG-C-C-G-A-A-A-U-A-M2G-C-U-C-A-G-D-D-G-G-G-A-G-A-G-C-m22G-psi-psi-A-G-A-C(m)-U-Gm-A-A-mlG-A-psi-C-U-A-A-A-G-m7G-U(D)-C-C-C-C-G-G-T-psi-C-A-mlA-U-C-C-G-G-G-U-U-U-C-G-G-C-A-C-C-AOH. Upon RPC-5 chromatography at pH 3.8 tRNA2Phe can be separated into four isoacceptors due to the partial modifications in positions 32 and 47. Thus the posttranscriptional modification of tRNA2Phe transcribed from one gene (or many genes with identical sequences results in four isoacceptors with the same basic sequence.


Future management of diabetes mellitus.

A review of therapies for diabetes mellitus reveals little that is new for the diabetic today. Also, there is little evidence that progression of diabetic complications can be slowed or halted with currently available therapeutic modalities that are acceptable to patients and can be applied in an everyday clinical setting. Few new drugs are likely to be ready for marketing in the immediate future, and most of the pharmacologic approaches that are now under study do not address the basic problem of lost sensitivity of the beta cell to endogenous glucose. In the longer term, it is likely that an oral insulin, allowing more convenient management of diabetes, will be available, as well as several new drug classes that may offer therapy adjunctive to insulin. As more is learned of the cellular physiology of the islet cell and the pathology of diabetes mellitus, some additional therapeutic breakthrough may occur. It is highly likely that an implantable or portable infusion system, either of the closed- or open-loop type, will be available when technologic problems are overcome. Islet cell transplantation may provide a definitive treatment for diabetes. At the very least, the questions should be resolved relating to careful physiologic control of the metabolic aberrations of diabetes mellitus. Unfortunately, because of the relatively slow evolution of diabetic vascular pathology, it will be several decades before current studies can provide the answers. If present hypotheses are confirmed, future therapeutic approaches can be more clearly defined; if the hypotheses must be rejected, the therapeutic dilemmas will remain.


Birmingham Medical Research Expeditionary Society 1977 Expediton: thyroid function and acute mountain sickenss.

In a study of 17 subjects plasma-thyroxine-binding globulin and plasma thyroxine concentrations rose during a high altitude trek. An early and sustained rise in plasma reverse triiodothyronine occurred independently of changes in plasma thyroxine and was probably related to physical exertion. Similar changes in thyroid function were found in subjects most affected and least affected by acute mountain sickness.


[The lung in monocional gammapatheis. Alternative hypotheses coming from a privileged observation (association of a diffuse interstitial fibrosis to a pulmonary tuberculosis then a disease of heavy gamma chains) (author's transl)].

The observation of a 61 year old woman who had a diffuse interstitial fibrosis, a pulmonary tuberculosis and a disease of heavy gamma chains is reported here. The different tumoral and infectious pneumopathies during monoclonal gammapathies are analyzed. In the opposite, there are the various abnormalities observed in thoracic pathology: chronic infections, pulmonary tuberculosis and diffuse interstitial fibrosis.


Synthesis of new benzophenone derivatives with potential antiinflammatory activity.

2-Methoxy-, 2-hydroxy- and 2-acetoxy-5-methylbenzophenones and their 5-carboxyl derivatives were synthesized and characterized by elemental analysis and IR spectra. The results of prostaglandin synthetase inhibition are reported for some of these compounds.


Studies on egg disinfection.

Various concentrations of alkyldimethylbenzyl ammonium chloride (QAC), Na2CO3, and ethylenediaminetetracetic acid (EDTA) were tested for antimicrobial activity singly and in combination against Escherichia coli, Arizona hinshawii, and Pseudomonas aeruginosa. Bactericidal activity of the reagents were evaluated in embryonating eggs, trypticase soy broth, and a medium containing lecithin. Toxicity of the chemicals was assayed in embryonating eggs. An appraisal was made of an egg-washing solution composed of 250 ppm QAC, 100 ppm Na2CO3, and 10 and 100 ppm EDTA. The mixture was effective and nontoxic for this purpose. All egg treatments had an adverse effect on fertility and hatchability. Using the temperature differential procedure in egg dipping, the disinfectant mixture was relatively nontoxic if 10 ppm EDTA was used with 3000 ppm tylosin tartrate. One hundred parts per million of the chelator in the dip solution caused excessive embryo mortality due to synergistic toxicity with the antibiotic. The germicidal action of the QAC solution was markedly increased with Na2CO3. Ten parts per million EDTA did not improve the biocidal effect of QAC solutions in distilled water but increased bactericidal activity in tap water that contained 16 ppm Ca and 22 ppm Mg.


Memory disorder in vertebrobasilar disease.

Previous workers have clearly established that the central core limbic structures of the brain are primarily concerned in the production of amnesia of the axial or mesial type. The blood supply to these structures derives primarily from the posterior cerebral circulation. This was the rationale for Benson's work on 'amnesic stroke' in patients with posterior cerebral artery occlusion. We have extended this concept to show that a similar axial amnesia, as demonstrated by a classical response on Wechsler Memory Scale testing, exists in patients with vertebrobasilar insufficiency. Relative permanency of the amnesic syndrome was demonstrated by repeat testing at may be of assistance in the diagnosis of vertebrobasilar insufficiency.


Increased nuclease activity in cells treated with pppA2'p5'A2'p5' A.

A series of 2'-5'-linked oligo(adenylic acid) triphosphate (2'-5' A) inhibitors of protein synthesis were described recently. These inhibitors are synthesized from ATP by an enzyme activated in interferon-treated cell extracts or rabbit reticulocyte lysates by double-stranded RNA. We show here that 2'-5' A is a potent inhibitor of protein synthesis in intact cells of different origin (human, monkey, hamster, and mouse). At a concentration of 10 nM (in AMP equivalents), protein synthesis is inhibited by 50-85%. There is also a secondary effect on the total RNA synthesis which becomes evident several hours after inhibition of protein synthesis. All of these effects, however, are transient and, after a recovery period, both RNA and protein synthesis resume rates comparable to the appropriate controls. A nuclease activity is detected in cells after treatment with 2'-5'A. The total polyadenylylated RNA is much reduced in comparison to that from untreated cells, and electrophoretic analysis in polyacrylamide slab gels provides evidence for its degradation. Similarly, there is an apparent degradation of ribosomal RNA. Consistent with these results, extracts from cells that had been treated with 2'-5'A manifest an enhanced nuclease activity in vitro on incubation with exogenous RNA. Here, we propose that, as in cell-free systems, the mechanism of action of 2'-5'A in intact cells involves activation of a nuclease. This activation is transient, but the nuclease remains sensitive to further activation by the inhibitor.


Chromosomal location of the genes for human immunoglobulin heavy chains.

We have studied somatic cell hybrids between P3x63Ag8 mouse myeloma cells deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and either human peripheral lymphocytes or human lymphoblastoid or myeloma cells for the production of human immunoglobulin chains and for the expression of enzyme markers assigned to each of the different human chromosomes. Human chromosome 14 was the only human chromosome present in all independent hybrids producing mu, gamma, and alpha human heavy chains. In two of the independent hybrids that produced human heavy chains, human chromosome 14 was the only human chromosome present in the hybrid cells. Loss of human chromosome 14 from these hybrids resulted in the concomitant loss of their ability to produce human immunoglobulin heavy chains. In view of these results, we conclude that the genes for human immunoglobulin heavy chains are located on human chromosome 14 in immunoglobulin-producing human cells.


Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene.

Immunoglobulin kappa chain gene formation involves site-specific somatic recombination between one of several hundred germ-line variable region genes and a joining site (or "J segment") encoded close to the constant region gene. We have cloned and determined the nucleotide sequence of major portions of the recombination region of the mouse kappa gene and discovered a series of five such J segments spread out along a segment of DNA 2.4 kilobases from the kappa constant region gene. These J segments encode the 13 COOH-terminal amino acids of the variable region, probably including amino acids involved in the antigen combining site and in heavy/light chain contacts. The J segments also display striking sequence homology to one another in both their coding and immediately flanking sequences. Major elements of a short palindrome--CAC(TA)GTG--are preserved adjacent to the recombination sites of both variable and J region genes and constitute inverted repeats at both ends of the sequences to be joined. These palindromes can be written as a hypothetical stem structure that draws variable and J regions together, providing a possible molecular basis for the DNA joining event. Four of the J segments that we have discovered encode amino acid sequences already found in myeloma proteins. By altering the frame of recombination, we can account for additional light chain amino acid sequences, suggesting that the V/J joining event might generate antibody diversity somatically both by using different combinations of variable and J region genes and by using alternative joining frames.


Abnormalities in clonable B lymphocytes and myeloid progenitors in autoimmune NZB mice.

Cloning procedures were used to study B lymphocytes and progenitors of granulocytes and macrophages in NZB mice. Numbers of B cells that were detected in sheep erythrocyte-containing semisolid cultures were only slightly elevated in NZB tissues, and these were normally sensitive to inhibition by anti-mu or anti-delta antibodies or prostaglandin E. However, NZB mice rapidly developed large numbers of B cells that could be cloned in the presence of lipopolysaccharide, and these included unusual anti-mu resistant cells. Numbers of myeloid precursors in NZB bone marrow that were responsive to colony-stimulating activity in L-cell conditioned medium or endotoxin serum were at least normal, but at all ages granulocyte-macrophage precursors were poor responders in cultures stimulated by WEHI-3 cell conditioned medium. Almost no colonies were elicited in NZB cultures with a colony-stimulating activity moiety from WEHI-3 cells. Prostaglandin sensitivity of myeloid precursors from NZB and CBA mice was also different. Codominant genetic control of these abnormalities was suggested by their partial expression in F1 hybrid NZB X CBA and NZB X NZW mice. NZB mice expressed an unexpected IgD allotype allele.


Assembly and secretion of pentameric IgM in a fusion between a nonsecreting B cell lymphoma and an IgG-secreting plasmacytoma.

A new immunoglobulin product has been obtained by hybridization of mouse cell lines arrested at different stages in B lymphocyte development. One line was shown to have the characteristics of an undifferentiated B cell that synthesizes monomeric IgM as a membrane receptor but does not express J chain. The second line was represent of a fully differentiated plasma cell synthesizing large amounts of IgG and J chain, but no IgM. Fusion of the two cell types yielded independent hybrid clones that secreted pentameric IgM, normally the first product of antigen-driven B cell differentiation. Analyses of the hybrid cells indicated that the IgM was expressed as a result of complementation between the synthetic capacities of the parental lines. The hybrid cells synthesized both monomeric IgM and J chain and assembled these components into a pentameric molecule with the expected stoichiometry of one J chain per five monomeric units. These findings provided further evidence that the induction of B cell differentiation includes a signal for de novo synthesis of the J chain. Moreover, the complementation achieved by this hybridization provides a system for identifying other intracellular events in B cell differentiation to IgM secretion.


Reciprocal stimulation of negatively selected high-responder and low-responder T cells in virus-infected recipients.

After depletion of alloreactive potential, immunologically naive T cells from C57BL/6J (Kb-Db) mice (B6) can be induced to respond to vaccinia virus in the context of both H-2Kk and H-2Db when stimulated in B10.A(4R) (Kk-Db) recipients. However, negatively selected B10.A(2R) (Kk-Db) T cells respond to H-2Db-vaccinia virus but not to H-2Kb-vaccinia virus when primed in an irradiated B6 environment. The B6 mouse strain is a high responder to vaccinia virus associated with H-2Db, whereas the B10.A(2R) and B10.A(4R) recombinants are low responders. Responsiveness in the context of H-2Db is thus recognized when the only homology between T cell and recipient is at the H-2D locus and is suppressed when H-2Kk is also present in both situations. The fact that negatively selected H-2Kb-Db T cells can be induced to recognize H-2Kk-vaccinia virus may reflect the existence of an "altered self" complex which is recognized via a single receptor, perhaps drawn from an alloreactive T-cell repertoire. At least in some instances, patterns of T-cell responsiveness are not totally constrained by the spectrum of H-2 antigens encountered in thymus.


Pyrazoles as inhibitors of alcohol oxidation and as important tools in alcohol research: an approach to therapy against methanol poisoning.

4-Methylpyrazole, in a dose producing inhibition of alcohol dehydrogenase (alcohol:NAD(+) oxidoreductase, EC 1.1.1.1), was given alone or together with ethanol (10%) as sole drinking fluid to growing rats for up to 38 weeks. Their weight curves remained normal. Electron microscopy of liver, kidney, and heart revealed no changes related to treatment. Hematologic analysis showed normal values for blood and bone marrow. Several clinical chemical parameters showed no impairment of liver or kidney function, except for an enhancement of the microsomal drug-metabolizing activity after concurrent administration of 4-methylpyrazole and ethanol. A study on rats receiving 4-methylpyrazole and ethanol indicated a mutual interaction of the two compounds or the metabolites, leading to increased concentration in the blood of the compounds and reduced formation of 4-hydroxymethylpyrazole, the primary metabolite of 4-methylpyrazole. In monkeys, elimination of 4-methylpyrazole followed a linear course. 4-Hydroxymethylpyrazole accumulated to a level of at most 10% of that of 4-methylpyrazole. Concurrent administration of methanol inhibited the elimination of 4-methylpyrazole about 25%, and 4-methylpyrazole produced a profound inhibition of the oxidation of methanol. 4-Methylpyrazole, at a level in the plasma of more than 10 muM, prevented accumulation of the toxic metabolite formic acid in methanol-poisoned monkeys, and repeated injections of 4-methylpyrazole abolished methanol toxicity in monkeys receiving lethal doses of methanol. The present investigation indicates that 4-methylpyrazole, with its low toxicity and strong inhibition of alcohol oxidation, is a valuable tool for experimental studies of alcohol metabolism and its effects. It illustrates the usefulness of the monkey as a model to study 4-methylpyrazole activity and toxicity in light of its possible use for treating methanol poisoning in human beings.


Effects of pseudomonas toxin A, diphtheria toxin, and cholera toxin on electrical characteristics of turtle bladder.

Rapidly developing changes in the short-circuiting current (Isc), conductance (G), and potential (PD) of turtle bladders in Na-rich or Na-free media are seen after the mucosal addition, at 10 nM, of each of three toxins that contain ADP-ribosylation activity: Pseudomonas aeruginosa toxin A, diphtheria toxin, and cholera toxin. Toxin A irreversibility decreased the Isc, PD, and G of bladders in Na-rich media and the Isc and PD of bladders in Na-free media. Diphtheria or cholera toxin reversibly increased Isc and PD (not G), but only in Na-free media. The effects of toxin A in the turtle bladder, like those in other host cell systems, were eliminated by preexposure of this toxin to heat, specific antitoxin, or dithiothreitol and urea. Because exposure to this last condition increases the ADP-ribosylation activity of toxin A, it is suggested that the proenzyme is the required transport-inhibiting form of toxin A. The effects of all three toxins occurred rapidly, possibly before any of the possible intracellular ADP-ribosylation reactions are initiated. Whereas a recognition binding of toxin of toxin to receptors on the apical membrane completely accounts for the reversible effects of diphtheria or cholera toxin, this and additional toxin-membrane interactions (e.g., translocation) are needed to account for the irreversible effects of toxin A.


Comparison of mRNA precursors in plasmacytomas producing closely related kappa chains.

To help elucidate the mechanisms of formation and expression of active immunoglobulin genes, we have made a systematic study of the processing patterns of the mRNAs that code for a closely related family of kappa chains. Among the members of this family, represented by the V(kappa)21 group of plasmacytomas, are examples in which six different germ-line V genes are joined to four different J segments in various combinations. The mRNA precursors were identified by hybridizing a cloned kappa-cDNA probe to poly(A)-containing nuclear RNAs that were size fractionated on methylmercury-agarose gels and transferred to diazotized paper. Based on the length of the segment excised in the last detectable processing step, which presumably represents the removal of the J-C intron, the precursor patterns were classified into four primary categories that correlated well with the type of J segment being expressed. The J segments were thus located at distances ranging from 2.4 to 4.8 kilobases from the constant-region gene. Different V genes joined to the same J segment exhibited similar precursor patterns, suggesting that the size of the translocated V segment may be relatively uniform among members of the V(kappa)21 group. A large (9.1 kilobases) component, which is likely to represent a primary transcription product, was observed in all processing categories, regardless of which J segment was being utilized. This surprising observation leads to some interesting predictions about the mechanism of V-J translocation.


Aspirin-like drugs interfere with arachidonate metabolism by inhibition of the 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid peroxidase activity of the lipoxygenase pathway.

Aspirin, indomethacin, and sodium salicylate are anti-inflammatory, analgesic, and antipyretic. Whereas aspirin and indomethacin inhibit prostaglandin synthetase (cyclo-oxygenase; 8,11,14-eicosatrienoate, hydrogen-donor: oxygen oxidoreductase, EC 1.14.99.1), salicylate does not. However, all three drugs affect the metabolism of arachidonate via the lipoxygenase pathway by inhibiting the conversion of 12-hydroperoxy- to 12-hydroxy-5,8,10,14-eicosatetraenoic acid.


Mutation in a structural gene for a beta-tubulin specific to testis in Drosophila melanogaster.

By two-dimensional gel electrophoresis of tubulins prepared from tissues of Drosophila melanogaster we have identified a beta-tubulin subunit that is present only in the testis. Furthermore, we have isolated, as a male sterile, a third chromosome dominant mutation [ms(3)KKD] in the structural gene for this beta-tubulin. Males heterozygous for this mutation produce no motile spermatozoa. Beginning with meiosis, all processes in spermatogenesis are abnormal to some extent. Many microtubules (including both cytoplasmic microtubules and doublet tubules of the axoneme) show aberrant structure in cross section, and the overall morphology of the developing spermatids is disorganized. Testes from these males were shown, by two-dimensional gel electrophoresis, to contain both the normal testis-specific beta-tubulin and an electrophoretic variant of this tubulin in equal amounts. Both wild-type and mutant testis-specific beta-tubulins were characterized by vinblastine sulfate precipitation, coassembly with purified Drosophila embryo tubulin, and peptide mapping.


Extrachromosomal control of mutability in Drosophila melanogaster.

Hybrid dysgenesis is a syndrome of germ-line aberrations including, e.g., sterility and mutation, found in certain interstrain hybrids of Drosophila melanogaster. Previous studies of sterility have shown that elements responsible for dysgenesis may reside on all major chromosomes, but that their dysgenesis-causing ability is controlled by an unknown extrachromosomal factor. Dysgenic hybrids also give rise to unstable visible mutations thought to be DNA insertions at certain sensitive loci. One such unstable allele at the singed bristle locus, designated snw, was found to mutate at extraordinary rates exceeding 50%. This instability was shown to be under the same extrachromosomal control as hybrid dysgenesis itself. That is, the mutability of snw was reversibly suppressed when placed in the background cytotype known to prevent sterility and other characteristics of hybrid dysgenesis. These results suggest that snw may represent an insertion at the singed locus of a hypothetical gene responsible for hybrid dysgenesis.


Effect of anti-HLA antisera on macrophage-T-cell interactions.

Human T lymphocytes were shown to proliferate in response to tetanus toxoid antigen only in the presence of macrophages. This response was inhibited by anti-DRw but not by anti-HLA (A and B loci) antisera added to the cultures and by pretreatment of macrophages but not of T cells with anti-DRw antisera and complement. Macrophages pulsed for 18 hr with antigen and then washed were capable of triggering T-cell proliferation. Addition of anti-DRw but not anti-HLA (A and B loci) antisera during the pulse period inhibited the macrophages' ability to trigger T-cell proliferation. The data obtained indicate that human T cells recognize and proliferate in response to antigen presented by the macrophages in association with Ia-like antigens.


Comparison of behavioral effects of systemic L-DOPA and intracranial dopamine in mesolimbic forebrain of nonhuman primates.

The systemic administration of L-DOPA and carbidopa to six rhesus and four squirrel monkeys produced an initial period of depressed activity followed by increased locomotion, hypervigilance, involuntary oral-facial movements and a gnawing syndrome. The squirrel monkey exhibited a depressed phase, locomotor stimulation, searching behavior, stereotypic grooming and gnawing syndrome. Most of these activities were prevented by pretreatment with 0.1 mg/kg haloperidol. Bilateral injection of 100 microgram dopamine into the mesolimbic forebrain of four squirrel monkeys also produced an initial depression followed by hyperactivity similar to that produced by L-DOPA, but without gnawing. A stereotyped submissive or juvenile posturing occurred in three animals. These DA-induced activities were blocked by 0.1 mg/kg haloperidol. Similar injection of 100 microgram L-norepinephrine produced a profound depression followed by moderate activity coupled with loss of extensor muscle strength in the legs. Bilateral injection of 300 microgram dopamine into the nucleus accumbens of a rhesus monkey produced stereotypic pacing. These data confirm in primates the importance of dopaminergic mechanisms of the mesolimbic forebrain in locomotor activity and behavior.


Reversal learning deficits in young monkeys exposed to lead.

The reversal learning capacity of young rhesus monkeys in visual discrimination tasks was examined during daily exposure to dietary lead acetate throughout the first year of life. While not affected in physical development, all lead-treated monkeys showed performance deficits on reversal learning tasks. These deficits were independent of lead-induced changes in motivation. Over a series of problems, the overall learning rate of monkeys with blood lead concentrations in the range of 70-90 microgram/dl was retarded, which resulted partly from a pronounced difficulty in attaining criterion on the first of a series of reversals within a given problem. This latter deficit resulted from an increase in errors, balks, and total trials to criterion on the first reversal. Monkeys exposed to blood lead concentrations of 40-60 microgram/dl required significantly more trials to finish all problems, but did not show the first-reversal deficit. Theoretical implications of these data were discussed.


Ethanol drinking by rhesus monkeys with concurrent access to water.

Three monkeys were provided concurrent access to water and ethanol in concentrations of either 8, 16 or 32% (w/v) during daily 3-hr sessions. The monkeys were those for whom ethanol had been established as a reinforcer in an earlier study in which only ethanol or water was available. Ethanol was preferred to water at all concentrations and volume of ethanol consumed was inversely related to ethanol concentration. Quantity of ethanol (g/kg of body wt.) consumed remained relatively constant, and blood ethanol determinations confirmed that the monkeys were drinking ethanol. Water drinking occurred at negligible levels except by one monkey at 16 and 32% who followed ethanol drinking bouts by water bouts (chasers) in a manner similar to that reported in other studies. Two monkeys were also provided concurrent access to 8% ethanol and water during 23-hr daily sessions. Under these conditions, ethanol was consumed every few hours to the near exclusion of water. The significance of this study lies largely in its procedure; that is, the development and application of a concurrent water-ethanol preparation in which ethanol serves as a reinforcer for rhesus monkeys. This preparation should be useful in the evaluation of a wide range of factors suspected to control alcoholic drinking.


Effects of phencyclidine, atropine and physostigmine, alone and in combination, on variable-interval performance in the squirrel monkey.

The role played by cholinergic activity in the effects of phencyclidine (PCP) on schedule-controlled responding was studied in three squirrel monkeys trained to respond on a variable-interval (VI) 100 sec schedule of food presentation. A low dose of PCP (0.08 mg/kg IM) produced small increases in rates of responding. Higher doses (0.16--0.64 mg/kg) produced dose-dependent decreases in rates of responding. Atropine (0.05--3.2 mg/kg IM) and physostigmine (0.025--0.20 mg/kg IM) caused only decreases in response rates, the dose-response curve for atropine being particularly flat over a wide range of doses. When atropine was combined with PCP, no significant interaction was obtained. When physostigmine was combined with PCP, a complex interaction was observed. Evidence fo partial antagonism of PCP by physostigmine was obtained only at the highest PCP dose tested. Atropine-physostigmine combinations resulted in response rates suggestive of antagonism.


Effects of response-contingent clock stimuli on behavior maintained by intravenous codeine in the rhesus monkey.

Response-contingent brief presentations of clock stimuli differentially correlated with food availability altered rates of codeine-maintained lever pressing. Rhesus monkeys performed under a two lever multiple schedule: Multiple fixed interval clock 5 min variable interval 2 min. Different colored lights were presented during successive 75 sec period of the fixed-interval clock component. Lever pressing under the FI Clock schedule was maintained by presentation of 1 g Noyes pellets, and lever pressing under the VI schedule by 0.05 mg/kg infusions of codeine PO4. Characteristic schedule-controlled performance developed in both schedule components. When the clock stimulus from the first or the final period of the FI Clock schedule was presented contingent upon completion of a short fixed ratio of responses during the variable-interval schedule component, the first clock stimulus decreased and the final clock stimulus increased rates of codeine-maintained lever pressing. Neither the first nor the final clock stimulus altered the frequency of codeine injection. The effect of each clock stimulus was accentuated by increasing the duration of stimulus presentation and by decreasing the response requirement for stimulus illumination. These rate-altering effects of the clock stimuli were most pronounced when different reinforcers were presented in the two components of the multiple schedule when either food or intravenous codeine injection was available under both components of the multiple schedule, response-contingent clock stimulus presentation did not alter response rates under the VI schedule.


The effects of antiasthmatic drugs against immune complex-induced bronchoconstriction in anesthetized dogs.

Bronchoconstriction was induced in nonsensitized dogs by intravenous injections of soluble immune complexes. Immune complex-induced bronchoconstriction was associated with a drop in blood pressure and a drop in the circulating complement levels. Different antiasthmatic agents were compared for their effects in dogs against bronchoconstriction induced by intravenous injections of immune complexes or histamone. Bronchodilators (isoproterenol, aminophylline, and bitolterol) inhibited both types of bronchoconstriction, whereas disodium cromoglycate, prednisone, and oxarbazole inhibited only bronchoconstriction induced by immune complexes. Thenyldiamine and atropine inhibited histamine- and carbachol-induced bronchoconstriction, respectively, but they were ineffective at the same doses against immune complex-induced bronchoconstriction.


[Neuroendocrinological changes under longterm therapy with lithium salts (author's transl)].

15 patients with formerly endogenous recurrent depression or manic-depressive illness free of psychotic symptoms, who are under lithium prophylaxis about 3,9 years, and 16 healthy controls with approximately the same age and sex were tested with 0,1 U Insulin/kg, 200 micrograms TRH and 50 micrograms LHRH for their hGH-, TSH-, hPRL-, FSH-, LH-and Cortisol levels about 2 hours. hPRL, FSH and LH did not show any change under lithium salts. All patients under lithium showed elevated TSH-levels under basal conditions and after stimulation compared with the control groups. For the young women before menopause the difference was highly significant. Men and praemenopausal women had significantly higher hGH-levels after stimulation under lithium than the normal controls. However postmenopausal women did not show this lithium effect on their hGH levels.


Object-related vs. narcissistic depression: a theoretical and clinical study.

This paper has focused on the sense of helplessness as an essential component of a depressive reaction. By inference, a sense of mastery and ability to achieve goals seems essential for a sense of well-being. Both patients presented here revealed infantile fantasies that hampered their exercising this mastery, and the path to well-being was the analysis of these fantasies. The treatment plans differed, though, in the locus of the fantasies. In an object-related depression such as Mr. Janson's, the fantasy involved the inhbition of functioning--that is, the inability to express aggression--and the treatment aimed at removing the inhibition. In a narcissistic depression such as Miss Gaynor's, the helplessness was not due to inhibited functioning per se. Rather, her goals were unrealistic, unattainable, and based on unconscious fantasies. Here the aim of treatment was the development of more reality-adapted and attainable objectives and the concommitant internalization of a more realistic sense of her own worth. Thus the common denominator in both depressive reactions was a sense of helplessness, and the path toward increased self-esteem was by way of the development of a sense of mastery and competence.


Reduction of MOPEG levels in cerebrospinal fluid of psychotic women after electroconvulsive treatment.

The effect of ECT on concentrations of monoamine metabolites in lumbar CSF of psychotic women with a schizophrenic symptomatology was examined. After a series of ECT there was a significant reduction of the concentration of the major noradrenaline metabolite, MOPEG. Levels of HVA, 5-HIAA, prolactin, or total protein in CSF were not significantly influenced by treatment. The results indicate a specific alteration of central noradrenaline metabolism in relation to ECT.


Effect of sulpiride on monoaminergic mechanisms in psychotic women.

Concentrations of the major monoamine metabolites homovanillic acid (HVA) 4-hydroxy-3-methoxyphenylethylene glycol (MOPEG), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in lumbar CSF of psychotic women with a schizophrenic symptomatology before and 4 weeks after treatment with sulpiride (Dogmatil 200 mg x 4). The metabolites were determined by a mass fragmentographic method. Prolactin concentrations in CSF and plasma were determined by radioimmunoassay. The clinical effects were evaluated by ratings according to the comprehensive psychopathology rating scale (CPRS) and a scale for side effects. Levels of HVA and prolactin in CSF and plasma were significantly elevated during treatment. No effects on concentrations of MOPEG or 5-HIAA were observed. The biochemical data indicate that clinical doses of sulpiride blocked dopamine receptors in the nigrostriatal pathway as well as in the tuberoinfundibular system. Treatment with sulpiride was associated with marked reductions in psychotic morbidity.


Inhibition of 5-HT uptake into neurons and platelets in mice treated chronically with chlorimipramine and femoxetine.

A single treatment with 5-HT uptake inhibitors potentiates the hypermotility in mice produced by the MAO-inhibitor nialamide. The effect of nialamide on motility was studied in mice after 4 weeks of feeding with a normal diet and diets containing various concentrations of the 5-HT uptake inhibitors chlorimipramine and femoxetine. Chronic treatment with the two substances enhanced the motor effects of nialamide about equally, which indicates a preservation of the neuronal 5-HT uptake inhibition during such treatment. The effect of chlorimipramine and femoxetine was obtained at plasma levels equivalent to or lower than the steady-state plasma concentrations found in patients treated with two 5-HT uptake inhibitors. Determination of decreased blood 5-HT after the 4 weeks of treatment was used as an in vivo test for inhibition of 5-HT uptake into platelets. Femoxetine was a much weaker depletor of blood 5-HT than chlorimipramine. These results indicate that blockade of neuronal 5-HT uptake is obtained at lower doses of femoxetine than blockade of 5-HT uptake into platelets. In contrast, chlorimipramine presumably inhibits 5-HT uptake into neurons and platelets at about the same dose.


Differential effects of nicotine and amphetamine on locomotor activity and maze exploration in two rat lines.

Separate groups of two different rat breeding lines, Roman High Avoidance (RHA/Verh.) and Roman Low Avoidance (RLA/Verh.), treated with either saline, nicotine (0.2 mg/kg), or amphetamine (0.4 mg/kg) were compared for exploratory efficiency and for exploratory locomotion by using two different mazes on alternate testing days. The RHA/Verh. rats generally showed more locomotion but less intermaze transfer of exploratory efficency than the RLA/Verh. rats. Nicotine did not alter exploratory efficiency but stimulated locomotor activity in the RHA/Verh. rats, while it did not significantly alter either category of behavior in the RLA/Verh. rats. Amphetamine stimulated locomotor activity in both rat lines but this stimulation was weaker in comparison with that of nicotine. In contrast to nicotine, amphetamine impaired exploratory efficiency in the RHA/Verh. rats. Like nicotine, amphetamine did not significantly affect exploratory efficiency in the RLA/Verh. rats. The results demonstrate that, when the two lines of rats are compared, there is a dissociation of the two categories of behavior and a further differentiation between nicotine and amphetamine effects.


Deficits of escape performance following catecholamine depletion: implications for behavioral deficits induced by uncontrollable stress.

Following exposure to inescapable shock, mice exhibit deficits of escape performance, which are progressively more pronounced as training continues. Comparable effects were produced by DA and NE depletion by alpha-MpT and reserpine, NE depletion by FLA-63, and DA receptor blockade through haloperidol. Treatment with PCPA or 5-HTP did not influence performance. The disruptive effects of reserpine and alpha-MpT, as well as haloperidol and FLA-63, were additive. Unexpectedly, mice that received both reserpine and FLA-63 exhibited escape latencies that were significantly lower than those of mice that received either treatment alone. Consistent with the view that increased DA synthesis in the reserpine plus FLA-63 condition prevented the escape interference, L-DOPA antagonized the effects of both alpha-MpT and FLA-63. The results suggest that DA and NE act in a serial fashion to produce the escape deficits. Moreover, although both newly synthesized and previously stored amines contribute to the interference, the short latency responses seen during initial test trials could not be ascribed to previously stored amines.


A rating scale for tardive dyskinesia.

A rating scale for tardive dyskinesia was developed, consisting of nearly all signs seen by two groups of investigators over a 5-year period. Thirty-four items were included in the scale with a possibility of writing in idiosyncratic signs. The scale was shown to have good reliability and validity in studies carried out by both the New York and Boston groups. It is recommended as a suitable instrument for describing the breadth of tardive dyskinesia syndrome and also for quantifying the disorder. A second scale, "the abbreviated dyskinesia scale", contains 13 items which are more global than the items in the original scale. It also has been shown to be both reliable and valid. Its use is suited to situations requiring less extensively detailed assessments.


Enhancement by chlordiazepoxide of the anticholinergic-induced locomotor stimulation in mice.

Spontaneous locomotor activity has been studied in mice treated with chlordiazepoxide, atropine, and scopolamine, given alone or in combination. Chlordiazepoxide alone increased activity for a short time, while the two anticholinergic drugs produced longer lasting stimulatory effects. Locomotor stimulation was stronger when chlordiazepoxide and anticholinergics were given in combination.


The effects of chlordiazepoxide on self-rated depression, anxiety, and well-being.

The main purpose of this study was to compare sensitivity of several self-rating scales to drug effects in anxious and depressed patients. Twenty-two distressed nonpsychotic outpatients completed a double-blind crossover trial of chlordiazepoxide and placebo. All self-rating scales of depression, anxiety, somatic symptoms, and feelings of inadequacy discriminated significantly between chlordiazepoxide and placebo. The decrease in self-rated depression was about equal to the decrease in self-rated anxiety. Subscales describing well-being were more sensitive to drug effects than subscales describing symptoms. A questionnaire (The Symptom Questionnaire) and one of the self-rating scales (Symptom Rating Test) were more sensitive than global self-rating scales, global observer-rating scales, and the Hamilton Anxiety Rating Scale. Some of the self-rating scales discriminated significantly between drug and placebo even when the sample size was reduced to two subsamples of eight patients each. High and significant positive correlations between two scales did not indicate equal sensitivity in discriminating between drug and placebo.


Serotonin uptake by blood platelets of acute schizophrenic patients.

Active uptake of serotonin by blood platelets of acute schizophrenic patients has been compared to that of a control group. Preliminary results presented in this article indicate that the uptake of the schizophrenic patients was about 40% lower than that of controls. Patients were followed over a period of 5 weeks with no significant change in uptake.


Modification of the behavioural effects of amphetamine by a GABA agonist in a primate species.

Acute administration of d-amphetamine in the marmoset results in a dose dependent increase in small head movements (checking), and an almost total suppression of purposeful activities and social interaction. It has little effect on locomotion and does not induce stereotyped gnawing. The GABA-agonist, muscimol, decreases checking, locomotion, activities and social interaction when given alone, but induces jerking movements at large doses. When administered in combination with amphetamine, muscimol induces persistent stereotyped gnawing. On the basis of the present findings and those of experiments in rodents it is suggested that compulsive gnawing results from overactivity in the striatal efferent pathway, while checking is probably mediated by extra-striatal sites. Since the behavioural effects of muscimol resemble those of the typical neuroleptics with the exception of the induction of gnawing, it is suggested that muscimol, though sedative, may counteract certain extrapyramidal effects of neuroleptic treatment while facilitating their other behavioural effects.


An associative analysis of pretreatment effects in gustatory conditioning by amphetamine.

Various attempts have been made to account for the fact that pertreatment with some pharmacological agents reduces the ability of such agents to induce conditioned aversion to a flavor. One explanation, based on the concept of tolerance, suggests that pretreatment is effective because it renders the animal less sensitive to direct effects of a given dose of the agent. A second explanation emphasizes the possibility that procedural consequences of pretreatment interfere with associability of flavor and drug effect during conditioning. The second explanation was tested in two experiments. In experiment I nonreinforced presentations of drug administration cues completely reversed the attenuating effects of amphetamine pretreatment on gustatory conditioning by amphetamine. This finding was replicated and extended in the second experiment which was also designed to eliminate an alternative nonassociative explanation for the results. The principle of associative blocking may explain the effect of pretreatment on subsequent gustatory conditioning by drugs.


Associative factors in drug pretreatment effects on gustatory conditioning: cross-drug effects.

The pretreatment effect (PE) in gustatory avoidance conditioning refers to the fact that pretreatment with a variety of pharmacological agents subsequently reduces the ability of the same agents to induce gustatory aversion. Explanations of this phenomenon emphasize either tolerance or associative interference. Any explanation of the phenomenon must also account for the present findings which demonstrate the PE when agents of pretreatment and conditioning were pharmacologically dissimilar. Rats were pretreated with d-amphetamine and tested for acquisition of an aversion to saccharin conditioned by amphetamine or morphine. The PE was obtained regardless of the drug used in conditioning. An associative manipulation involving nonreinforced presentation of the drug administration cues (i.e., injections followed by saline instead of drug), that attenuated the PE when pretreatment and conditioning were with amphetamine, was also effective when the pretreatment agent was amphetamine and the conditioning agent was morphine. The findings were interpreted within a framework of compensatory conditioning of a general physiological mechanism common to all gustatory avoidance.


Behavioral activities of opioid peptides and morphine sulfate in golden hamsters and rats.

The behavioral effects of beta-endorphin, [D-Ala2, D-Leu5]-enkephalin and morphine were investigated in golden hamsters and in rats. In golden hamsters, beta-endorphin and [D-Ala2, D-Leu5]-enkephalin induced loss of righting reflex, whereas morphine caused no such effect. Both opiate peptides and morphine caused the inhibition of tail-flick response and catalepsy in rats. beta-Endorphin was the most potent, followed by [D-Ala2, D-Leu5]-enkephalin and then by morphine. The catalepsy induced in rats by [D-Ala2, D-Leu5]-enkephalin was different from that of beta-endorphin and morphine in that it produced catalepsy without muscular rigidity. beta-Endorphin and [D-Ala2, D-Leu5]-enkephalin caused hypothermia in golden hamsters; morphine was less active in altering the body temperature. beta-Endorphin caused hypothermia at high doses and hyperthermia at low doses in rats. These heterogenous behavioral responses indicate that multiple types of receptors mediate the effects of opiates in the central nervous system.


Behavioral effects of low, acute doses of d-amphetamine on the dyadic interaction between mother and infant vervet monkeys (Cercopithecus aethiops) during the first six postnatal months.

Doses of d-amphetamine sulfate (0.1, 0.15, and 0.2 mg/kg body weight) were given to adult monkeys in mother-infant pairs. The fundamental parental care behavior pattern was disrupted and the mother became isolated in a socially withdrawn phase. She did not respond to the calling signals of the infant and showed behavior in which stereotyped self-grooming and/or 'staring' into space were predominant. The reactions of the infant to this amphetamine-induced behavior were different in the two experimental pairs. In group 1 the infant increased its approach--avoidance movements. In group 2 the infant sat very quietly and close in front of the mother. The mother from group 1 reacted to the increased approaches from its infant with active rejection. In both groups the mothers did not react with the typical ventral--ventral grasping to either the infants sitting close or to the social anxiety signals of the infants. In spite of differences in behavior changes induced by amphetamine, the main conclusion is that the mothers totally lost their normal and highly biologic significant interest in their infants.


A comparative trial of the decanoates of flupenthixol and fluphenazine.

A double-blind trial was carried out comparing the effects of decanoates of flupenthixol and fluphenazine on the symptoms, ward behaviour and functional capacity in occupational therapy in 51 chronic schizophrenic patients. The patients were carefully selected on the basis of rigid criteria for diagnoses. To exclude nonresponders to neuroleptics the patients were first taken off neuroleptic drugs and only those who appeared to show deterioration were included in the trial. The dosage of drugs was varied according to clinical indications. The length of the trial was initially 4 months and 31 patients were followed for an additional 4 months. To ensure reliability multiple assessments were made at the start and the end of the trial. Most of the statistical tests showed no differences between the treatments, but some of those relating to affective symptoms showed an advantage for flupenthixol as compared with fluphenazine. There were no differences in the incidence of extra-pyramidal side-effects which required treatment in only 32% of the patients on each drug.


Different cigarette-smoker classification factors and subjective state in acute abstinence.

On each of 4 days after abstaining from cigarettes and other psychoactive materials for at least 10 h, 48 male cigarette smokers reported their mood before smoking the first cigarette of the day. Smokers were classified both by relative desire for smoking in situations inducive of high arousal or low arousal and by average daily consumption. Greater relative desire for smoking in high-arousal situations was associated with an abstinence syndrome of dysphoria. Compared to smokers with low consumption, medium-heavy smokers showed higher levels of tension-anxiety and were less deactivated while at the same time they were more fatigued and sleepy, indicating different relationships with different components of multifactorial arousal. Effects related to levels of cigarette consumption may have been confounded by tea/coffee withdrawal, however, abstinence states disappeared on smoking.


GABA-mediated behavioral inhibition during ontogeny in the mouse.

Although immature rats and mice generally demonstrate poor behavioral inhibitory capacities, some recent evidence may indicate the presence of substantial inhibitory control. The present experiment investigated the possibility that gamma-aminobutyric acid (GABA) systems may mediate some behavioral inhibition during early development. Mice 9-100 days old were injected with the GABA-elevating agent amino-oxyacetic acid (AOAA) and tested for behavioral activity. High levels of locomotor activity characteristic of immature control mice were attenuated following AOAA injection, whereas AOAA had little effect on the activity of adult mice. Moreover, AOAA produced a period of rebound hyperactivity for young but not for adult mice. These findings suggest that although GABA systems may mediate early behavioral inhibition, coordination between excitatory and inhibitory capacities matures slowly. In a second experiment the dopamine-beta-hydroxylase inhibitor FLA-63 prevented rebound hyperactivity in young mice pretreated with AOAA, suggesting that the excitatory component may be mediated by noradrenergic systems.


The effect of cannabidiol, alone and in combination with ethanol, on human performance.

Fifteen volunteers received cannabidiol (CBD) (320 microgram/kg) or placebo (both orally, T0), and 60 min later they consumed an ethanolic beverage (0.54 g/kg) or placebo. The effects were measured at T1 (100 min after CBD ingestion), T2 (160 min) and T3 (220 min) using cognitive, perceptual and motor function tests. Factorial analysis indicated that test procedures could be adequately expressed by three rotated factors: A reaction speed factor (I), a standing steadiness factor (II) and a psychomotor coordination/cognitive factor (III). Ethanol produced a significant decrement in factor III. There was no demonstrable effect of CBD, either alone or in combination with ethanol. Neither CBD nor ethanol produced any significant effect on pulse rate. Prior administration of CBD did not significantly affect the blood ethanol levels. Whilst the subjects were able to identify correctly when they were given ethanol, they did not report any subjective effects of CBD.


Facilitation of self-stimulation with high doses of amphetamine in the rat.

Rats were trained to self-stimulate by interrupting a photobeam and brain stimulation was maintained for as long as the beam of light was broken. d-Amphetamine sulphate was then administered and response rate and total duration of stimulation were recorded. Both response rate and total duration were elevated by 1.0, 2.0, and 5.0 mg/kg dosages. The 1.4 s/response duration observed with saline was elevated to 2.0 s/response with 2.0 and 5.0 mg/kg doses. It was concluded that amphetamine's effects on self-stimulation are at least partially determined by the response requirements of the task employed.


[Esophageal intramural pseudodiverticulosis (author's transl)].

Esophageal Intramural Pseudodiverticulosis (EIP) is a very rare disease, which may affect patients of all age. EIP is characterized by dilatation of the esophageal submucosal glandular elements. The characteristic radiographic appearance supported by endoscopy makes the diagnosis. Stenosis and motility disturbance caused by secondary chronic esophagitis due to EIP were found in most patients. The etiology of EIP is unknown.


[Radiotherapy of esophageal cancer (author's transl)].

There is general agreement on the effectiveness of radiotherapy in the treatment of squamous cell carcinoma of the esophagus and the advantage of rotation technique with conventional as well as supervoltage therapy. The use of small fields in order to reduce the possibility of damage to neighbouring structures requires a more accurate positioning of the target than the use of large fields. In kilovoltage therapy this was guaranteed by controlling the field by fluoroscopy and by the possibility for correction during irradiation. This accuracy and possibility for correction is not yet reliably obtainable in supervoltage therapy as demonstrated by the number of complications reported. In the future, more fractionation, possibly using a higher initial dose, followed by hyperthermia, should be contemplated in order to reduce the total dose. The combination with chemotherapy deserves further development as well. For the treatment of operable tumors, preoperative irradiation with 2000-3000 rads immediately followed by resection is again recommended.


[Prognostic criteria and clinical prerequisites of curative therapy of esophageal cancer by radiotherapy alone (author's transl)].

Survey of 289 patients with squamous cell carcinoma of the esophagus treated solely by irradiation between 1961 and 1973. All patients fit for radiotherapy -- uniformly without further selection -- received a local dose of at least 6500 rads. This resulted in a 18% one year survival rate; only one patient lived more than five years. All patients were compared using different criteria to correlate the initial findings at the time of diagnosis with the type of therapy and the prognosis. Three treatment plans were established according to the initial clinical findings: a) palliative therapy, b) locally curative therapy and c) radical curative therapy. The treatment plan which seems to show the best results consists of preoperative irradiation with adjuvant chemotherapy followed by surgical removal of the tumor. This plan should be pursued in all appropriate patients.


[Radiotherapy of esophageal cancer -- any improvement in prognosis? (author's transl)].

Results of radiotherapy (42 MeV-Beta-tron) on 93 patients with esophageal cancer treated between 1969 and 1976 are reported and compared with those in the literature (on orthovoltage- and telecobalt-therapy). Complete remissions occured in 29%; the one -- and two-year-survival-rate for all 93 patients was 38% and 24% respectively, and for patients with complete remission 74% and 44% respectively. Although there was improvement in complete remission and short term survival compared to that reported in the literature, the five-year-survival-rate (only about 5% of patients) showed no significant improvement.


[Radiographic findings after duodenal surgery (author's transl)].

A gastroduodenostomy as part of partial gastric resection may change function and morphology of the duodenum in a typical fashion. End to side anastomosis may produce a blind pouch. An end to end anastomosis may lead to postanastomotic dilatation, which may mimick a duodenal bulb (a so called "neo -- or pseudobulb"). Abnormal duodenal peristalsis with atony may follow vagotomy, pyloroplasty, gastroduodenostomy or excisional duodenal biopsy and may thus result in functional obstruction. A blind loop syndrome may develop after bypass procedures for duodenal stenosis.


Mesenteric vascular effects of prostaglandins F2 alpha and B2. Possible advantages over vasopressin in control of gastrointestinal bleeding.

Mesenteric vascular effects of prostaglandins B2 and F2 alpha were studied and compared to those of vasopressin in the dog, cat and baboon. Vasopressin reduced superior mesenteric blood flow (SMBF) 80-100%, and significantly increased hepatic arterial blood flow and systemic arterial pressure. Prostaglandin B2 produced vasodilatation at low doses and biphasic vasodilatation/vasoconstriction at high doses. Prostaglandin F2 alpha elicited only vasoconstriction, reducing SMBF, left gastric, and inferior mesenteric blood flow 80-100%. Systemic arterial pressure was not significantly changed. Thus, vasopressin and prostaglandin F2 alpha are equally effective mesenteric vasoconstrictors. Because of reduced systemic effects, prostaglandin F2 alpha has excellent potential as a mesenteric vasoconstrictor to control gastrointestinal hemorrhage.


Comprehensive analysis of a Radiology Operations Management computer system.

The Radiology Operations Management computer system at the Hospital of the University of Pennsylvania is discussed. The scheduling and file room modules are based on the system at Massachusetts General Hospital. Patient delays are indicated by the patient tracking module. A reporting module allows CRT/keyboard entry by transcriptionists, entry of standard reports by radiologists using bar code labels, and entry by radiologists using a specialty designed diagnostic reporting terminal. Time-flow analyses demonstrate a significant improvement in scheduling, patient waiting, retrieval of radiographs, and report delivery. Recovery of previously lost billing contributes to the proved cost effectiveness of this system.


Electron-beam arc therapy using a high energy betatron.

Dose distributions in electron-beam arc therapy were investigated using the electron beam from a Brown Boveri 45 MeV betatron. This variable isocenter machine is equipped with an angular speed control device that synchronizes the radiation dose rate with the rotation speed about the isocenter. An Alderson Rando phantom was used with Kodak RP/V film to measure isodensity distributions that were then converted to isodose curves. The effects of varying field size, isocenter depth, and air gap between collimator and phantom were examined, along with changes in the dose distributions produced by wax bolus in part of the arc.


The comparative survival of clonogenic cells of a murine epithelioma irradiated in vivo with 250 kVp X rays, 60Co gamma rays, or negative pions produced by the cyclotron at TRIUMF.

Squamous carcinomas in WHT/Ht mice were exposed to the biomedical pion beam at TRIUMF. The biological effects of the pion beam were compared to those of 250 kVp x rays. The dose rates were 2-3 rad/min. (.02-.03 Gy/min.) for pions and 56 rad/min. (.56 Gy) for x rays. The surviving fraction of epithelioma cells irradiated in vivo was studied using the TD50 assay. RBE values for pions were calculated from the ratio of the x-ray and pion D0 values and were found to be 1.6 +/- 0.3 for oxic cells and 2.1 +/- 0.4 for hypoxic cells. OER values were 1.8 +/- 0.5 for pions and 2.4 +/- 0.4 for 250 kVp x rays.


Bremsstrahlung dose to patients in rotational electron therapy.

Dose and integral dose from bremsstrahlung in a 10-MeV electron beam were measured for irradiation of large areas with 120 degrees-arc rotational fields. The maximum bremsstrahlung dose ranged from 2% to 7% of the maximum electron dose for the different beam arrangements, while the integral dose showed the same range of variation. The concomitant bremsstrahlung beam should be collimated by the x-ray photon collimators and the use of narrow field rotations avoided.


Synthesis and biological properties of 9-deoxo-16,16-dimethyl-9-methylene-PGE2.

The in vivo monkey uterine stimulating potency of 9-deoxy-16,16-dimethyl-9-methylene-PGE2 is similar to that of 16,16-dimethyl-PGE2 and approximately 15 times that of PGE2. Low doses of this compound stimulated uterine contractions when administered vaginally. Pregnancy was terminated prematurely following subcutaneous, intramuscular or vaginal suppository treatment. Estimates of potential for gastrointestinal side effects using the rat enteropooling assay and in vivo monkey effects indicate that diarrhea will be substantially reduced with retention of uterine stimulating potency.


Pear malic enzyme: some physical and immunochemical properties.

Some physical and immunochemical characteristics of NADP malic enzyme from climacteric pear (Pyrus communis L. var Passe-Crassane) are described. The enzyme which has a molecular weight of about 224 000 d and a sedimentation coefficient of about 9.6 S, is formed by the association of four sub-units. We were not able to isolate isozymes by electrophoresis or by immunochemistry.


[A study of 95 families having at least two epileptic children (author's transl)].

This report concerns a study of 95 families in which at least two of the children had epilepsy (a total of 210 cases). A total of 45 p. 100 of the patients were from 60 p. 100 of the families and had an intellectual level below the average, and 32 p. 100 of them had an IQ below 70. The family history was the same whether the children were mentally deficient or not. There was no family history of mental deficiency in those families where the epileptic children had a normal IQ but there was a positive family history in 25 p. 100 of families having at least one mentally deficient and epileptic child. The persistence of seizures after 5 years of treatment is seen much more frequently in mentally deficient children than in those with normal intelligence. Finally, the position of the child within the family has no influence and epilepsy may be found in any of the children.


[Experimental study of the effect of membrane oxygenators on the pulmonary structure of the dog and monkey (author's transl)].

Six dogs and 5 monkeys were subject to extracorporeal circulations with membrane oxygenators for various time periods (from 4 to 57 hours). The pulmonary samples, examined with electron microscopy, enabled us to control the appearance of lesions (similar for the two animal species) and to follow their evolution. From the second hour, abnormalities of the capillary endothelium were observed; but at the 6th hour, the lesions had already deeply affected the whole pulmonary structure and became more and more serious. This intrinsic toxicity of membrane oxygenators on the pulmonary structure should incite extreme caution in the use of this method in man.


Development of acute dystonia and tardive dyskinesia in cebus monkeys.

In 4 out of 11 cebus apella monkeys given haloperidol (0.05 - 1.0 mg/kg/d) orally for up to 35 months signs of tardive dyskinesia (TD) hav developed: 1) One monkey developed barely noticeable TD after 4 months, but showed marked and increasing symtpoms of both generalized choreic and buccolingual TD after 8 months. This animal died 3 months after discontinuation of haloperidol. At that time the signs of TD were still prominent. 2) In one monkey bucco-lingual TD appeared after 3 months and was still reversible on discontinuation of haloperidol at 5 months. After a further 12 months of haloperidol, the TD signs proved to be long lasting, possibly irreversible, in this animal. 3) A third monkey showed slight and transient signs of TD at 14 months, but following a further 20 months af haloperidol administration a choreiform syndrome became porminent after drug withdrawal. 4) After 34 months a similar syndrome of choreic movements has been noticed in another animal, increasing after withdrawal of haloperidol. The other 7 monkeys have received haloperidol for 3 - 15 months, without developing any signs of TD. Attacks of acute dystonia have been noticed in all animals, sometimes necessitating anticholinergic medication or decreases in the daily haloperidol dose.


The intensive care of acute pancreatitis.

The results of medical and surgical treatment of 115 cases of acute pancreatitis treated in the surgical intensive care unit over a period of 8 years are reviewed. The death rate from acute pancreatitis fell during the period of study in the intensive care unit from 42.6% between 1969 and 1973, when drainage was used, to 22.9% between 1974 and 1976 when resection was performed, and in hospital from 8.2% to 5.8% respectively. The results improved as a consequence of adequate treatment of shock, complete intravenous feeding, accurate timing of surgery and the successful choice of operative procedures.


[Use of the BG 15 autoanalyzer for automatic recording and determination of ABO, Rhesus and Kell blood groups].

The use of the 15 channels blood grouping autoanalyzer with automated recording and interpretation proved its fiability through more than 30 000 tests for ABO, Rh and Kell determinations. Misreactions come mostly from the carry-over phenomenom. However no discrepancy was noticed for ABO determination. Only few ones occured for Rhesus and Kell, leading to false positive interpretations which were always corrected by checking the event recorder track. New improvements are expected from the automatic phasing using a microprocessor and further extents are setting up with the connection to a computer.


[Epidemiologic studies about the allergic diseases (author's transl)].

Three large epidemiological studies in Birmingham over a period of 20 years showed a significant increase in the prevalence of asthma in children. Children of immigrants from the West India and Asia had a low prevalence if born abroad, but as high a prevalence as European Children if born in England. The age of onset of asthma and eczema is earlier than that of maximum appearance of skin reactions to common allergens. Among atopic children, 35% have raised levels of IgG4. These children respond poorly to cromoglycate and usually need steroids. Those with eczema have high levels of both IgG4 and IgE. Asthmatic children are more frequently born between May and October compared with the general population. This excess of birth of asthmatic children in Summer is due to mite sensitive children. The excess of births in Summer is not related to hay fever or to pollen sensitivity.


[Evolutive patterns of diffuse pleural mesothelioma (author's transl)].

The clinical beginning of diffuse pleural mesothelioma is a pleurisy. Initially pleura may be normal at X-ray examination, then either a pachypleuritis or a tumorous pleura appears. Thery serious since there is in the literature no cured case. The average survival time from diagnosis to death is 15 months. At terminal stage mesothelioma does not invade the other coelomic cavities. It may remain limited to the hemithorax where it has started, invading then the organs by contiguity. Metastasis may occur but their frequency is very variable, from 30 to 70% according the literature. On a therapeutic point of view all was tried: Surgery is rarely curative but may reduce temporarily effusion pain and dyspnea. Radiotherapy at high doses produces a partial effect in some series, but results are variable. Chemotherapy: adriamycin could be the most promising agent. At present time according to many authors no treatment seems to change the course of the disease.


Cholestatic hepatitis induced by gold.

A patient with rheumatoid arthritis developed an acute intrahepatic cholestasis after 100 mg of sodium aurothiomalate. Hepatotoxicity in rheumatoid arthritis is well described following a variety of anti-inflammatory preparations but is now a rare complication of gold therapy and the literature on the subject is reviewed.


[Immunological approach to asthmatic disease (author's transl)].

Research into the environmental factors in the aetiological diagnosis of asthma is a fundamental measure which must direct complementary test and therapy. Extrinsic asthma is mostly found in young people, with atopic antecedents. Immunological study is based on the clinical history and skin tests (IgE dosage, in vitro tests and provocation tests are difficult to apply in epidemiology due to their high cost). In children 3/4 of asthma cases are extrinsic. Differential diagnosis is especially a problem with rhinitis. There is only a small percentage of cases of non atopic extrinsic asthma which can  bring other immunological mechanisms into play. So-called intrinsic asthma (late onset asthma, with continuous dyspnea, corticodependent) is mostly observed in adults. The age has an influence on the severity of the attacks, the curve of asthma with permanent dyspnea being a function increasing with age, whereas that of less severe asthma is a function decreasing with age. The role of extrinsic factors does not seem important in this category of asthmatics (10 to 25% according to the statistics). Immunofluorescence studies of the bronchial mucosa show up the possibility of local immunological reactions, whether specific or not (frequent presence of the C3 complement). This means that the immunologist can, in many cases of asthma, help the epidemiologist to define and to understand the physiological mechanisms of the disease.


Labelling of human and rabbit platelets with 111Indium-oxine complex.

Platelets suspended in buffer were labelled with 111Indium-xoine. In the isolation procedure the platelets and a fraction of the erythrocytes are processed simultaneously, whereby the erythrocytes serve as a supporting cushion in the centrifugation steps. Various factors which influence the labelling effectiveness were examined, and the method's utility was estimated by in vivo studies in rabbits. A platelet concentration of more than 800 x 10(9)/1 and an oxine concentration of approximately 6 micrograms/ml in a plasma-poor system (transfer of platelets from plasma to buffer without further washing steps) will yield a high labelling efficiency. If the platelet isolation yield is to be large, a slight erythrocyte-leucocyte contamination must be accepted. Our experimental results indicated that this is permissible. In vivo investigations of 5 rabbits showed in vivo recoveries of platelets from 61--74% and mean survival times from 69 h to 110 h. This supports the assessment that the method of platelet isolation and labelling is gentle.


Lymphocyte blastogenesis studied by volume spectroscopy.

The blastogenesis of human blood lymphocytes has been studied by measuring the distribution of cellular and nuclear volumes in concanavalin A (Con A)-stimulated leucocyte cultures by means of a modified Coulter counter. Agglutinated and adherent cells were dispersed by 3 h of incubation with alpha-methyl-mannoside and EDTA. Fresh suspensions contained 5--35% monocytes with an average cellular volume 2--2.5 times that of small lymphocytes. The nuclear volume of monocytes was similar to that of small lymphocytes within 10% and remained constant upon stimulation. In cultures given the optimal dose of Con A, 30 micrograms/ml, measurable cell growth commenced within 8--12 h, whereas nuclear growth began some 6 h later, which is approximately 6--8 h before increased 3H-thymidine incorporation could be detected. The average volume of responding cells grew by a factor of about 4 until mitosis, which started after around 48 h, whereas the average nuclear volume increased by a factor of about 3. The percentage of cells responding by volume growth increased with mitogen concentration even for hyperoptimal concentrations (150 micrograms/ml) which strongly suppressed 3H-thymidine incorporation. The results exemplify the type of information obtained by volume spectroscopy of leucocyte cultures. This method appears to have several advantages over conventional assays of immune response.


Analbuminemia (a quantitative albumin variant).

Serum albumin accounts for over 50% of total serum protein and contributes to a significant extent to homeostasis through such crucial functionas as colloid osmotic pressure, transport, and nutrition. Analbuminemia was first described in 1954, but only 13 additional cases have since been reported. A further case, a 30-year-old Italian women, has been recently detected by the authors. Contrary to expectations, the large majority of analbuminemic subjects appear clinically well, the only consistent finding being a slight tendency to develop ankle edema. Asthenia and moderate hypotension have been recorded in several cases. Although associated disease conditions have been described in isolated instances, no clear-cut connections have been established with the analbuminemic state. Laboratory features include increased circulating levels of cholesterol, beta-lipoproteins and esterified fatty acids, as well as elevation of acute phase reactants and immunoglobulins. Albumin turnover studies have usually shown that both mechanisms of albumin synthesis and catabolism may be impaired in these subjects. Consanguinity of the percentage is a common feature and transmission as an autosomal recessive trait has been suggested. Thus, analbuminemia appears as an exceptional 'experiment of Nature', in that it challenges the vital role of circulating albumin.


Effects of sodium aurothiomalate on hyaluronic acid synthesis in normal and rheumatoid synovial fibroblast cultures.

In studies with normal and rheumatoid synovial fibroblast cultures the effects of sodium aurothiomalate on the quantity and quality of hyaluronic acid were tested. This gold compound produced one clear effect: the molecular weight of hyaluronate produced by rheumatoid fibroblasts was increased (shifted towards normal) whereas the effects on the amounts of hyaluronic acid synthesized were small in both rheumatoid and control cultures. The importance of this finding in relation to the known beneficial effects of gold preparations in clinical medicine is discussed.


Admission and discharge indicators as aids in optimizing comprehensive rehabilitation services.

This paper describes the development of a theoretical cost effectiveness model used to optimize admission and discharge decisions in comprehensive rehabilitation centers. Rehabilitation progress and outcome is conceptualized in terms of functional gains due to treatment. The model is constructed with three variables: functional level at admission (Barthel), Barthel function gained per unit cost (BUC) and the percentage improvement in function from admission to discharge. The theoretical model is then tested with data from a random sample of 97 spinal cord injured and 132 focal cerebral patients drawn from ten leading comprehensive rehabilitation centers located across the continental United States. The basic structure of the model is supported by the data and the use of such models as aids in managing patients, evaluating services, planning new programs, and developing computer simulation models of rehabilitation cost effectiveness is discussed.


Priapism as a complication of long-term intravenous nutrition.

A case of priapism following prolonged intravenous nutrition is reported. The small amounts of heparin as received by our patient would tend to minimise a risk of hypercoagulability. However, the administration of intravenous feeding agents and the concomitant metabolic acidosis may have enhanced this risk.