Use of cromolyn in combined gastrointestinal allergy.

A double-blind clinical trial was undertaken to evaluate the efficacy of orally given cromolyn sodium vs that of pacebo in the management of food allergy. Fourteen children, aged 2 to 15 years, with milk allergy and concomitant allergies to one or more foods were given cromolyn or placebo. Eleven had positive intradermal skin reactions or coproantibodies to offending antigens. Treatment was begun while the children were receiving elimination diets; they were challenged with specific antigen only after 48 hours of drug administration. Crossover took place if the initial agent was ineffective. Cromolyn afforded protection in 11 of 13 trials, whereas placebo was effective in only three of nine trials. By chi 2 analysis, the drug's effect was statistically significant.


Surgical treatment of the radiation injured bowel.

Over the last 10 years, 9 patients treated by surgical procedure for radiation injuries of the bowel were studied with the following conclusions: The damage to the small intestine caused by external irradiation leads to adhesion of the bowel, perforation and postoperative anastomotic dehiscence if the irradiated bowel is used in the anastomosis. Surgical treatment for the small intestine is resection of the damaged loop. In order to determine the extent of the resection it is important that during the operation fibrosis and obstruction of vessels in the submucosa and subserosa is examined by biopsy. On the other hand, rectal ulcer and/or rectovaginal fistula is chiefly caused by intracavitary application plus external irradiation. For these lesion Hartmann operation or colostomy is performed, and the postoperative course is uneventful.


Response of canine mast cell tumors to radiation.

Twenty-three dogs completed a fractionated course of ionizing radiation therapy for mast cell tumors. In 10 dogs the response was satisfactory, and the tumors were considered controlled 12 months after completion of the prescribed course of therapy. Treatment was considered unsatisfactory for the remaining 13 dogs due to failure to control the tumor locally, generalized metastasis, or both. A dose effect was noted in the response of the tumors to radiation. Of 6 dogs, 5 responded satisfactorily when the tumor dose was 4,000 rads or greater. When the tumor dose was less than 4,000 rads, 5 of 17 dogs responded satisfactorily. The dose calculated to control 50% of the meat cell tumors was 3,625 rads (95% confidence interval: 3,265-4,024 rads). Adverse normal tissue reactions, which consisted of moist desquamation in 10 animals and necrosis in 4, were recorded. The dose calculated to cause desquamation in 50% of the dogs was 3,750 rads (95% confidence interval: 3,348-4,200 rads).


[Extracardiac effect of nitroglycerin in chronic ischemic heart disease according to the study of microcirculation].

Study of the dynamics of circulation in the microvessels of the eye conjunctiva under the effect of nitroglycerin in 50 patients with chronic ischemic heart disease showed short-lived dilatation of the postcapillaries and venules in most of them. Simultaneous fall in venous pressure may be evidence of a diminution of the venous tonus with a tendency to the storage of blood in the microcirculation system. The encountered shifts in the systemic hemodynamics may possibly be due to the reaction of the microcirculation channel, the labile character of which in the various "micro-areas" of the conjunctiva testifies to the complex reorganization of microcirculation under the effect of nitroglycerin.


[Supplementary intravenous nutrition in term and preterm neonates (author's transl)].

16 term and preterm neonates received intravenous nutriton for at least three days. The dosage was 1--2 g amino acids, 1 g of fat, and 8--10 g glucose per kg body weight and day. Compatibility was investigated by daily determinations of the amino acid pattern in the serum and measurement of free fatty acids and triglycerides. All results were compared to five neonates who were fed completely orally from the first day of life. Leucine, methionine, proline, and valine levels were elevated during intravenous nutrition, but only the high methionine levels were regarded as a nutrional imbalance. Free fatty acids and triglycerides showed no significant differences as compared to the control group.


Do dollars spent relate to outcomes in burn care?

In light of limited health care funds, there is a need for reliable information relating costs to clinical outcomes. Distinction should be made between diseases for which improved outcomes relate to intensity of care and those for which limits of current knowledge preclude improved results. A survey of 1,656 burn admissions to 73 hospitals over a one-year period showed that length of stay, unpaid bills, and the proportion of unpaid bills to total bills were two to six times greater than for nonburn admissions to the same hospitals. Three hospitals had special burn facilities, and even when adjustments were made for severity of injury, these hospitals had poorer outcomes and higher costs when all their burn patients were studied. When only those patients with greater than 30 per cent burn were compared between hospitals with and without special burn programs, or when patients were matched for degree of burn the hospitals with the special programs still had no better patient outcomes than those without such facilities. The crucial question, then, is whether mortality and complications were lower in special facilities. Although there was no evidence in this survey that they were, the final answer must come from a prospective study of outcome. If these survey results are confirmed, burns might be identified as an illness for which current limits in management abilities limit the ultimate proportion of successful outcomes.


[Treatment of the syndrome of inappropriate antidiuretic hormone secretion with demethylchlortetracycline (author's transl)].

A patient with a syndrome of inappropriate antidiuretic hormone secretion secondary to an undifferentiated bronchogenic carcinoma with distant metastases was treated with demethylchlortetracycline. Up until recently, treatment of this syndrome was based on water restriction and when the plasma sodium concentration became extremely low, hypertonic saline solution administration. Recently it has been demonstrated that the antibiotic demethylchlortetracycline inhibits the action of the antidiuretic hormone on the renal tubules. The drug has been used successfully in five patients with the syndrome of inappropriate antidiuretic hormone secretion. The administration of 900 mg of demethylchlortetracycline per day for 7 days in our patient produced an increase of free water clearance, diuresis, plasma sodium concentration, and plasma osmolarity. Urinary excretion of sodium and urinary osmolarity declined. Furthermore, the neurological symptoms attributed to hyponatremia improved markedly. The patient lost 6 kg during treatment, probably because of negative water balance induced by demethylchlortetracycline. Even though the administration of demethylchlortetracycline did not produce significant decreases in the glomerular filtration rate or renal blood flow in our patient, it is advisable to control the renal function in individuals treated with this drug since it may on occasion determine renal insufficiency.


[Effect of nitrogen-containing compounds on hydrogen light emission and nitrogen fixation by purple bacteria].

The cells of Rhodospirillum rubrum and Thiocapsa roseopersicina grown in media containing glutamate and arginine, respectively, as well as under conditions of nitrogen fixation evolve H2 in the light. If the cultures were grown in media with NH4+, NO3-, urea, glutamine or asparagine, hydrogen photoevolution by the cells and acetylene reduction started after the lag-phase and proceeded at a low rate. Extracts of such cells did not display the activity of nitrogenase which could be assayed by the ATP-dependent evolution of H2 from dithionite. The data obtained confirm the fact that hydrogen photoevolution by purple bacteria involves nitrogenase whose synthesis is regulated (according to the action of glutamine) with the participation of glutamine synthetase. NH4+, glutamine and asparagine inhibit also hydrogen photoproduction by purple bacteria and acetylene photoreduction. However, they have no effect on hydrogen evolution in the dark by the cells of R. rubrum and T. roseopersicina in the presence of formiate or pyruvate, respectively, whereas carbon monoxide inhibits hydrogen production. Therefore, hydrogen production by purple bacteria in the dark must be catalyzed by hydrogenase.


CT and nuclear medicine in screening for neurological disease.

Unit costs of computerized tomography (CT) in Australian hospital practice are considerably lower than those reported in the United States' literature, and not significantly higher than those of nuclear brain scanning which is at a threefold to fourfold disadvantage in false negative rates. CT is cost-effective not only in defining but in screening for neurological disease, and should replace radionuclide scans in both roles.


[Use of urea by purple bacteria].

Strains of purple sulfur bacteria (Chromatium minutissimum, Ectothiorhodospira shaposhnikovii, Thiocapsa roseopersicina, Lamprobacter modestohalophilus) and nonsulfur bacteria (Rhodopseudomonas palustris, Rh. spheroides, Rhodospirillum rubrum) grow in media containing urea as a source of nitrogen at concentrations from 0.5 to 5.0%. They can also utilize the carbon of urea and thus grow in the absence of bicarbonate. Urea is decomposed by all the studied purple bacteria with the participation of urease. In a number of strains, the enzyme is inducible and is synthesized only in the presence of urea. However, it is constitutive in certain purple bacteria (L. modestohalophilus, Rh. palustris, Rh. spheroides). The strains of purple bacteria differ in the activity of urease and in its susceptibility to ammonium ions.


[Electron microscopic study of thylakoid structure in cyanobacteria].

Two or three thylakoids can be detected in Synechococcus elongatus, strain 58, and Plectonema boryanum if sections are successful. Peripheral thylakoids sometimes seem to be connected with the cytoplasmic membrane. Partitions and septa, as well as small electron-dense granules typical of cells which underwent lysis, are found in the intrathylakoidal space. Branching of thylakoids is described. Particles 16 and 11 nm in size whose possible nature is discussed can be discerned on the fracture faces. Phycobilisomes have not been discovered by the technique of freeze-etching.


[Clinical evaluation of cefazedon on patients with urinary tract infections (author's transl)].

The efficacy and tolerance of Cefazedon, a new antibiotic, was investigated clinically on 90 patients with urinary tract infections who also required surgical treatment. Good clinical results were achieved in over 90% of patients after 6 to 7 days of treatment. The bacteriological examination revealed complete elimination of the initially identified pathogens in 89 cases. No difference in treatment results could be established when applying the dose 2 or 3 times daily. On the third day of treatment skin reactions were observed in one case which necessitated discontinuation of treatment. Laboratory blood values as well as control of liver and kidney function before treatment, after and one week past treatment showed no negative influence due to the drug. In approximately 27% a new colonisation mainly with Pseudomonas could not be prevented.


[Changes in the ultrastructures of Anacystis nidulans cells at different temperatures].

If the cells of the blue-green alga Anacystis nidulans are put in the unfavourable conditions, the pairs of photosynthetic membranes separate, vacuoles are formed within thylakoids, and degradation of the photosynthetic apparatus occurs the earlier the sooner photosynthetic electron transport stops functioning: after 7--9 days in the dark, after 7--10 days in the light at 5 degrees C, after 5--7 days at 45 degrees C. If the cells are incubated at 5 and 45 degrees C, they become longer and form rods upto 10--12 mcm in length; at 45 degrees C, degradation takes place and the cell contents separate. The stationary phase of growth in the optimal conditions at 37 degrees C takes more time and the cells are degraded only after 45 days. If the temperature is lowered to 20 degrees C in the light, the cells remain viable for a long time and are degraded only after 60 days. In these conditions, invaginations of photosynthetic lamellae appear in the living cells, and the activity of TTC reduction in the light remains high for a long period of time. The cell wall remains intact upon degradation in remains high for a long period of time. The cell wall remains intact upon degradation in all the variants. Pigments are not destroyed both at a high (45 degrees C) and low (5 degrees C) temperature longer in the dark than in the light; therefore, photodestruction is involved in degradation of the lamellar apparatus in the light. The order in which pigments decompose differs depending on the conditions: chlorophyll is the first to be destroyed at 5 degrees C, phycocyanin at 45 degrees C, chlorophyll and phycocyanin at 37 degrees C; the rate of degradation of all pigments is almost the same at 20 degrees C. Apparently, additional pigments play different role in the processes of degradation occurring in the light.


[Resistance to tetracycline and doxycycline in Bavaria (author's transl)].

The in vitro sensitivity of tetracycline and doxycycline is compared. Streptococcus and staphylococcus are more sensitive to doxycycline whereas pseudomonas and proteus spec. are more sensitive to tetracycline.


Cytological changes related to Brucella canis variants uptake in vitro.

In this study, evidence for in vitro uptake, invasion, and cytopathogonomic effects of normal and variant strains of B. canis on tissue culture, is presented. B. canis L-phase were penicillin-induced and these microorganisms produced revertants on penicillin-free media. Tissue culture (LLC-MK2) cells were divided into different normal and variant-infected groups (I-IV), including controls. Bright-field and electron microscopic observations indicated uptake of all the strains and recognizable host cell damage (CPE) to varying degrees. At 72 h after infection, the extent of damage by L-phase was the least (55.5% CPE). The L-phase-derived revertants resulted in 80% damage; this approximates the adverse effect of normal B. canis (85%). In addition to these gross changes, various structural abnormalities, including pyknosis, nuclear disorganization, vacuolation, and karyorrhexis, were apparent. The implications of these findings and the indirect role of the L-phase in brucellosis due to B. canis are discussed.


Simple method to detect virus-specific IgM antibodies in patients' serum samples after immunosorption of immunoglobulins G and A.

By absorption with protein A and specific immunosorption using insolubilized adsorbentia (CPG), a method was developed for rapid elimination of IgG and IgA from patients' serum samples. This test technique was examined in the diagnosis of rubella infections, i.e., rubella-specific IgM antibodies. The procedure has proven to be as reliable as determinations carried out with IgM fractions separated on a sucroe density gradient.


Dosimetric properties of neutrons from 21-MeV deuteron bombardment of a deuterium gas target.

Spectra, yields, average energies, and kerma rates in tissue of neutrons from 21-MeV deuteron bombardment of deuterium gas targets have been calculated for target thicknesses of 1, 3.5, and 5 MeV. A high pressure gas cell was constructed and was filled with 33 atm of D2 gas (equivalent to an energy loss of 3.5 MeV for 21-MeV deuterons); dose rate, dose buildup, and depth-dose properties of neutrons produced by the D(d,n) reaction were measured. Dosimetric properties of these neutrons are superior to those of neutrons from a thick Be target bombarded by a deuteron beam of the same energy.


Choosing a therapy electron accelerator target.

Angular distributions of photon depth dose produced by 25-MeV electrons incident on several fully stopping single-element targets (C, Al, Cu, Mo, Ta, Pb) and two composite layered targets (Ni-Al, W-Al) were studied. Depth-dose curves measured using TLD-700 (thermoluminescent dosimeter) chips embedded in lucite phantoms. Several useful therapy electron accelerator design curves were determined, including relative flattener thickness as a function of target atomic number, "effective" bremsstrahlung endpoint energy or beam "hardness" as a function of target atomic number and photon emission angle, and estimates of shielding thickness as a function of angle required to reduce the radiation outside the treatment cone to required levels.


Some perspectives on the transfer of cell-mediated immunity by immune-RNA.

Ribonucleic acid extracts of lymphoid cells from immune hosts were used to transfer in vivo and in vitro cell-mediated immune reactivity to a variety of antigens. The in vivo immune responses transferred by RNA included the delayed cutaneous hypersensitivity reaction to fungal and chemically-defined antigens and the tumor-rejection reaction to guinea pig hepatoma antigens. The in vitro immune responses transferred by RNA included macrophage migration inhibition by fungal, chemically-defined, and tumor antigens. The transfer activity of RNA preparations was contained in the 8 s to 18 s species of RNA and was sensitive to RNase but not to DNase or trypsin. Antigen was not detectable in the RNA preparations and appeared to have no role in the transfer activity. Syngeneic, allogeneic, or xenogeneic sources of RNA could transfer immune reactivity. In each system tested, the transfer of cell-mediated reactivity by RNA was specific for the antigen used to sensitize the RNA donor. The potential use of RNA-mediated transfer of immunity is discussed.


Insulin sensitivity of liver glycogen synthase b into a conversion.

Liver glycogen synthase b phosphatase, chromatographically separable from phosphorylase a phosphatase, is decreased in 48-hour alloxan diabetic rats. The phosphatase activities are measured in an in vitro system using exogenous isolated phospho-enzyme as substrates with added phosphatases. Synthase and phosphorylase phosphatases were shown to have differential catalytic properties by their reactivity in the presence of Pi, the heat-stable inhibitor of phosphorylase phosphatase and after incubation with added cAMP-dependent protein kinase.


[Neurological cardinal symptoms of internal diseases (author's transl)].

The old rule:"Frequent is frequent, Seldom is seldom" is only true of etiological entities. With symptoms and syndromes which are hastily diagnosed as "typical" or "atypical" just because they are frequent, serious misdiagnoses may occur and critical details both in the history and in the physical examination may be overlooked. The terminal reaction of the body, i. e. the phenomenological entities are a principium cognoscendi for the doctor as for the patient they are principium agendi which send him to the doctor. The task of the neurologist is to set out the neurological cardinal and warning symptoms as signposts for a satisfactory internist investigation and to a jointly controlled therapy.


[Syncope. An important border-line between neurology and internal medicine (author's transl)].

It is important for the neurologist to know the variations of the Adams-Stokes's attack so that the important differential diagnosis between an epileptic reaction and an Adams-Stokes's attack due to cardiac rhythmic disorder can be made. The Adams-Stokes's syndrome is not only due to asystoles in the sense of cardiac arrest but also to ventricular fibrillation and especially to the very common syndrome of the pathological sinoauricular node. The great importance of digitalis overdose is pointed out as an eliciting factor for the kind of arrhythmia which runs a course similar to that of the Adams-Stokes's syndrome.


[Encephalopathy and liver diseases (author's transl)].

As the central organ of metabolism the liver is of the highest importance for the nervous system and for the brain in particular, which only becomes apparent under pathological conditions. It is of importance to neurologists that for them the differential diagnosis of subclinical or chronic intermittent decompensating types of hepatic encephalopathy is predominant. We are actually concerned here with encephalomyeloneuropathies which become manifest by failure on the part of the spinal marrow and the peripheral nervous system. Among the various hepatocerebral diseases the rare Wilson's disease and sporadic Wilsonismus should be mentioned from the differential diagnostic point of view, and especially the differential diagnosis of the porphyrias should be given attention, since they may first appear spontaneously and suddenly under metabolic stress, e. g. anesthesia.


[Bowen carcinoma following many years' use of a "radium cushion" (author's transl)].

A case is reported of a 73-year old female patient in whom precancerous symptoms appeared in the mid-abdominal area of application which for a long time were mistaken for chronic eczema, until after 7 years the development of a skin carcinoma was clinically and histologically confirmed. The case provides a reason to draw attention to the "Radium Cushion" and to restate publicly that they should be delivered to the health authorities. Suspected cases must be thoroughly investigated medically.


[Prevention of urinary tract toxicity of oxazaphosphorines by a "uroprotector". Report on a field study (author's transl)].

In an open multicenter phase III trial, prophylaxis of the urinary tract with sodium 2-mercaptoethanesulfonate (Mesnum) was carried out in 242 patients treated with oxazaphosphorines for various malignant tumors. Under the protection of Mesnum 29 patients were treated with cyclophosphamide (Endoxan), 195 with ifosfamide (Holoxan) and 8 with trofosfamide (Ixoten). Other cytostatics were also used (polychemotherapy) in 92 cases. On administration of Mesnum, 7 macrohematurias reappeared, only 3 of them however with correct application, and 22 microhematurias, 12 of them with correct application. Cylindrurias were re-established in 3 patients. In Mesnum we have a compound which can control the urotoxicity ("uroprotector") of oxazaphosphorines which limits their therapeutic use.


[Treatment of chlamydial urethroadnexitis with erythromycin (author's transl)].

Chlamydia are primarily to be considered as possible pathogens in abacterial urethroadnexitis besides mycoplasma and ureaplasma. Beside these, yeasts, trichomonads and herpes viruses play a subordinate role only. Treatment with with erythromycin is promising. This is shown in the comparison of the concentrations we found by the Blenk and Blenk MIC determinations in serum, in material expressed from the prostate and in urine.


[Surgery of the hand--a medical duty (author's transl)].

The considerable technical progress in surgery of the hand, especially in the field of microsurgery which made replantation of detached fingers possible, may give the impression that hand surgery is primarily a technical discipline. It is intended to show that besides the technique, surgery of the hand includes many other important factors such as assessing the natural facts and taking into account the biological possibilities. But especially important is concern for the patient. This doctor-patient relationship in hand surgery is decisive for the result.


[Mountain sickness or alpine climber's disease (author's transl)].

The symptoms of mountain sickness extend from slight malaise to severe clinical disease. From our own observations in the Himalayas the most serious symptoms appear at night, i. e. at less than the meximum height achieved and when physically at rest. The etiology is not completely clear; the reduced oxygen partial pressure at a height plays a principal role. Prophylactic measures are empirical, scientific methods are being worked on. Treatment is symptomatic, causal therapy consists of rapid removal from the height and oxygen respiration.


[Infusion solutions: a controllable factor in hospital costs (author's transl)].

The development of costs for fluid treatment in a general hospital during four years is reported. A considerable lowering of costs could be attained by reduction of proprietary specialities without dispensing with individual therapy. Problems arising are discussed.


[Stress among businessmen (author's transl)].

An enquiry was conducted into the stress problems of 118 independent businessmen in Switzerland aged between 24 and 67 years. 19% were receiving medical treatment compared with 21% of 1260 representatively registered employed men from 44 random samples from factories in North Switzerland. About one third of the treatment diagnoses were due to stress conditions. 45% of those registered were smokers, 14% of them pipe smokers. 57% were overweight. 91% took exercise, 19% of them for up to 10 hours weekly. 2% described the general feeling of stress as very strong, 29% as strong, 36% as medium and 31% as weak and 11% none at all. Only 4% admitted very severe or severe family stress, 16% medium, 23% slight and 57% none, but 21% complained of very great or great business stress, 34% medium, 33% slight and only 11% none.


[Neurosurgical aspects of cerebral ischemia (author's transl)].

Besides purely conservative treatment and cerebrovascular surgery, the extra-intracranial bypass operation forming an end-to-end anastomosis between the superficial temporal artery and a cortical branch of the middle cerebral artery offers a neurosurgical possibility for therapy. The indications for this operation lie principally in the transitory cerebral ischemic attacks, the precursors of ischemic insults. In contrast to this the indications for the microneurosurgical vascular interventions possible in the regions supplied by the vertebral and basilar arteries cannot presently be comprehensively defined.


[Dental aspects of atypical neuralgia in the maxillofacial region (author's transl)].

The complicated anatomy of the masticatory system with its coordinated functional elements offers a multitude of noxae for atypical neuralgias. More specifically, affections of the pulp, apical periodontopathies with cyst formation, impacted teeth, aggressive osteopathies and malignant growth come into consideration. In addition, dysfunctional unions must be borne in mind. The styloid syndrome also deserves attention. Because of this causal complex the discovery of other puzzling painful conditions needs dental investigation.


[Advances in the conservative treatment of acute traumatic cerebral edema. Controlled clinical trial with follow-up examination (author's transl)].

Studies in 142 accident victims with severe craniocerebral trauma showed that the intravenous application of sodium escinate over several days considerably reduced the dangerous rise in intracranial pressure and also the total mortality in comparison with corticosteroid therapy alone. Both groups, each of 71 patients, were adjusted from an initial intraventricular pressure of 500--250 mm H2O to the same basic pressure of 150 mm H2O hydrostatically. In the same way, sodium escinate shortened the duration of unconsciousness. The renal function in patients was good. Follow-up examinations at least 2 to a maximum of 3.5 years after the accident and treatment showed a significantly higher rehabilitation rate in the sodium escinate group.


[Computer tomography on the pancreas. A diagnostic extension from the surgical aspect (author's transl)].

125 patients were subjected to computer tomography on account of suspected pancreatic disease. 48 patients were operated on--the computer tomography (CT) diagnosis was confirmed in 85.5% of the cases. Acute pancreatitis can be detected by CT if it is accompanied by an appropriate enlargement of the organ. Chronic pancreatitis can be recognized by deformations of the organ, calcifications or formation of pseudocysts. Pancreatic carcinoma is recognizable when it is larger than 3 cm accompanied by a change in the shape of the organ or if infiltration of neighboring structures has occurred. Computer tomography offers patients a safe, non-invasive method of performing follow-up examinations at short intervals.


[Medical secrecy and the pathologist's obligation of notification (author's transl)].

The pathologist, like every other doctor, is pledged to secrecy. The pledge of secrecy also extends to what he has found in the body of the deceased be they secrets of the patient or of a third party. Third party secrets are not protected by the obligation of secrecy if safequarding them would be against the "projected interests of the patient". The present obligation to notify according to the burial laws of some states applies to pathologists even when possible medical contributary faults are established, but he faces a dilemma which cannot be solved juridically at present. Alteration of the law should take this into account.


[Recommendations for transfusion therapy. Volume substitution, raising oxygen transport capacity and replacement of clotting factors (author's transl)].

The principal aims of whole blood transfusion therapy are simultaneous volume substitution, raising the oxygen transport capacity and the replacement of clotting factors. The necessary control factors for volume substitution are described. It must be borne in mind that the blood undergoes changes during storage which among other things affects the ability of the blood to transport oxygen and the clotting potential. Not only the destruction of thrombocytes must be considered but also the loss of activity of the proaccelerin and the antihemophilic globulin A. For this reason for massive blood transfusions using older blood conserves it is recommended that the loss of activity be compensated by antihemophilic cryoprecipitate.


Induced nondisjunction in drosophila oocytes.

Nondisjunction of the sex chromosomes and compound-second chromosomes was induced in Drosophila melanogaster by irradiation of immature oocytes and cold treatment of mature oocytes. These two treatments cause nondisjunction by different mechanisms. This results in a differential for stage sensitivity and the production of relatively different frequencies of the various exceptional progeny classes.


Trenimon: biochemical, physiological and genetic effects on cells and organisms.

The trifunctional alkylating mutagen Trenimon interferes with the genetic material of a variety of organisms and test systems with respect to the induction of point and chromosomal mutations, sister-chromatid exchanges, recombination phenomena and phage induction. Beneath these mutagenic effects several biochemical and cell physiological aspects have been investigated. In this review we discuss chemical and cell physiological effects of Trenimon, aspects of cancer therapy with Trenimon and genetic effects induced by Trenimon. The available data on mutagenic effects of Trenimon are presented according to organisms or test systems. A short discussion on a possible genetic load by therapy with Trenimon in man concludes this review. DNA damage, especially the induction of cross-linkings, seems to represent the common reason for most of the described effects of Trenimon on cells and organisms.


Prevention of thrombosis in patients on hemodialysis by low-dose aspirin.

Since platelet cyclo-oxygenase is much more sensitive to inactivation by aspirin than is the enzyme in the arterial wall and low doses of aspirin may prevent thrombosis by blocking thromboxane synthesis, we conducted a randomized, double-blind trial of aspirin (160 mg per day) vs. placebo in 44 patients on chronic hemodialysis. The study was continued until there were 24 patients with thrombi and both groups had been under observation for a mean of nearly five months. Thrombi occurred in 18 of 25 (72 per cent) of patients given placebo and 16 of 19 (32 per cent) of those given aspirin (P less than 0.01). The incidence of thrombosis was reduced from 0.46 thrombi per patient month in the placebo group to 0.16 thrombi per patient month in the aspirin group (p less than 0.005). A dose of 160 mg of aspirin per day is an effective, nontoxic antithrombotic regimen in patients on hemodialysis.


Life history and histopathology of ultraviolet light-induced skin tumors.

The life history and histopathology of UV light-induced skin tumors were studied in NMR rats, outbred female Swiss mice, and Syrian golden hamsters. High intensity UV light of medium wavelengths produced hyperplasia and papillomas, as well as a dysplastic, intermediary solar keratosis-like stage, with distinct cellular atypia leading to several types of squamous cell carcinomas. High doses of UV irradiation of short duration caused scars, which developed into fibromas and fibrosarcomas composed of "light" and "dark" cells. Carcinomas with neoplastic squamous and fibrous components were uncommon; however, collision tumors with two components were occasionally seen. Angiomas and angiosarcomas with a proliferating endothelial structure were observed, but adnexal tumors, with follicular or sebaceous differentiation, and basal cell carcinomas were infrequent. Pigment cell tumors were found only rarely. The number of tumors and tumor-bearing animals at different stages of the experiment were also studied. Tumors were compared with lesions induced by chemical carcinogens in different systems. UV carcinogenesis was characterized by many tumor-bearing animals, but with a low total tumor count and a high mortality, thereby decreasing the number of animals-at-risk. The tumor types, their progression from on type to another, and the distribution of certain biologic characteristics were also analyzed. We concluded that UV irradiation is an effective tumor inducer in animal skin, and the type of tumor, its behavior, and location depend on the experimental conditions.


Insulin release by tolbutamide and glibenclamide. A comparative study on the perfused rat pancreas.

Glibenclamide, a "second generation" sulfonylurea, produced the same pattern of insulin release from the perfused rat pancreas as did tolbutamide. The stimulatory effect was closely dependent on the glucose concentration present. Both agents enhanced insulin secretion at 5--10 mM glucose, whereas no additional insulin was released when maximally stimulating levels of glucose (20 and 30 mM) were present. The concentrations of glibenclamide stimulating insulin release were 100--400 times lower than equieffective levels of tolbutamide. At glucose levels of 3 or 8 mM, however, glibenclamide did not liberate significantly more insulin from the pancreas than did tolbutamide. Thus the differences of tolbutamide and glibenclamide were quantitative rather than qualitative. Although the active concentrations differed the effects produced were comparable.


Hypothalamic thyrotropin-releasing hormone and maternal plasma TRH-peptidase activity in protein-deficient and food-restricted pregnant rats and their fetuses.

This study examined the effects of protein deficiency and food restriction on hypothalamic TRH in pregnant rats and their fetuses. The absolute and relative amounts of TRH in hypothalami were not significantly changed by diet in either dams or fetuses. Plasma TRH-peptidase activity in the dam was significantly reduced by protein deprivation, whereas food restriction caused a lesser reduction. Fetal hypothalamic TRH was less affected by maternal malnutrition than was fetal body size.


[Case of intrapancreatic duodenal diverticulum].

A case of intrapancreatic duodenal diverticulum is presented and the possibility of pancreatitis is considered. A digital manoeuvre is described for the non-invasive location of a large diverticulum in case where Kocher's manoeuvre is insufficient. The usefulness of surgery as a mean of preventing what may prove dramatic complications is recognised.


Prophylaxis of minor febrile and major infectious morbidity following hysterectomy.

A retrospective analysis was conducted of 668 consecutive cases using T-tube suction drainage and/or prophylactic antibiotics as infection prophylaxis for hysterectomy. The data are analyzed for the incidence of minor febrile morbidity (temperature greater than 100.4 for 2 days) and for major infection (hospital stay more than 14 days, reoperation or readmission for the management of pelvic abscess or pelvic thrombophlebitis). The study also compares a minor febrile and major infection group with a noninfected group by measuring parameters of patient discomfort, medical staff effort, and financial costs. It is concluded that 1) minor febrile morbidity frequently follows abdominal (20--30%) and vaginal (30--50%) hysterectomy; 2) minor febrile morbidity has temporary but significant consequences in the form of increased patient discomfort, medical staff effort, and financial costs; 3) major infections are rare following abdominal hysterectomy (less than 0.5%) and uncommon following vaginal hysterectomy (1--4%); 4) suction drainage used alone, prophylactic antibiotics used alone, or a combination of suction drainage and antibiotic prophylaxis is each associated with a statistically significant reduction in the incidence of minor febrile morbidity following both abdominal and vaginal hysterectomy (P = less than 0.01); and 5) such infection prophylaxis may also reduce the incidence of major infection following vaginal hysterectomy.


Effects of piperonyl butoxide on the toxicity and hepatocarcinogenicity of 2-acetylaminofluorene and 4-acetylaminobiphenyl, and their n-hydroxylated derivatives, following administration of newborn mice.

Neonatal ICR/Ha mice were injected subcutaneously with a single dose of 25, 50 and 100 microgram of 4-acetylaminobiphenyl (AAB), N-hydroxy-4-acetylaminobiphenyl (N-OH-AAB), 2-acetylaminofluorene (AAF), or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) alone or together with 2,5% piperonyl butoxide (PB) in tricaprylin, negative control groups were injected with tricaprylin, and positive control groups were injected with 30 microgram of 7,12-dimethylbenz(a)anthracene (DMBA), alone or with PB. PB induced synergistic toxicity in the various groups of mice injected with the nonhydroxylated and hydroxylated amine carcinogens, or with DMBA, as compared with groups injected with carcinogen alone. AAB, N-OH-AAB, AAF, and N-OH-AAF all induced dose-related hepatocarcinogenicity in male, but not female mice, which was not consistently influenced by concomitant administration of PB. DMBA control groups developed pulmonary adenomas and lymphomas in both sexes, and hepatomas in males, whose incidences were not modified by PB.


Extraction and identification of a human pancreatic-tumor-associated antigen.

In attempting to develop an immunoassay to aid in the early diagnosis of cancer of the pancreas, a pancreatic-tumor-associated antigen (TAA) was identified and partially purified. The antigen has a molecular weight of approximately 380,000, does not cross-react with carcinoembryonic antigen (CEA), and is apparently either not present or not readily detectable in normal pancreatic tissue. The development of an immunoassay employing such an antigen to aid in the diagnosis of cancer of the pancreas at an early stage of development is discussed.


Comparison of Dycal and formocresol pulpotomies in young permanent teeth in monkeys.

This study compared Dycal and formocresol pulpotomies on young healthy permanent teeth with respect to continued dentinogenesis and root end development. Pulpotomy was performed on a total of forty permanent teeth with incompletely developed roots in three young stump-tailed monkeys (Macaca speciosa). Twenty teeth were treated with Dycal and twenty with formocresol. At the end of the experimental periods the animals were killed and the specimens were prepared and sectioned en bloc for histologic examination. The interval between treatment and death ranged between 7 and 797 days. Before each experimental procedure a Procion vital dye was administered as a marking agent for continued root development. Twelve of twenty teeth treated with Dycal and seventeen of twenty teeth treated with formocresol were judged to be successful as evidenced by continued root development, absence of periapical pathoses, and the presence of noninflamed or only mildly inflamed pulps. Brown and Brenn staining showed bacteria within the pulps of the teeth that failed. All but one of the teeth in this study showed evidence of continued root development as confirmed by Procion labeling.


The surgical biopsy.

A cost-benefit analysis of biopsy techniques for deep cervical lesions reveals that the aspiration biopsy is superior in terms of cost, speed, and morbidity but inferior in accuracy. Aspiration is most accurate for the diagnosis of metastatic carcinoma in cervical lymph nodes. An early diagnosis of malignancy by needle aspiration can be of benefit in several stages of patients management.


Conservative surgical management of tracheal stenosis.

Tracheal stenosis has become an increasing complication following tracheostomy or prolonged intubation for mechanical ventilation and is directly related to trauma. Tracheal resection up to 4 to 5 cm with end-to-end anastomosis is the generally accepted treatment. However, tracheal resection carries mortality and considerable morbidity. From 1974 to 1977 all patients seen with tracheal stenosis, regardless of the etiology and age, were initially treated with a conserative surgical management. It consists of dilation, severance of the stenotic ring, intralesional injection of triamcinolone acetonide, and stenting with a silicone T tube for 90 days. Nine out of 11 patients had good results and enjoy an adequate airway without a tracheostomy tube. The longest follow-up is three years and the shortest is eight months. Intralesional injection of triamcinolone acetonide is essential for a successful treatment. No serious complications due to this treatment have occurred. This technique appears worthy of trial prior to contemplating a more extensive procedure.


Acute mastoiditis and cholesteatoma.

Acute coalescent mastoiditis is an uncommon sequela of acute otitis media. It occurs principally in the well-pneumatized temporal bone. The findings of fever, pain, postauricular swelling, and otorrhea are classic. Cholesteatoma, on the other hand, being associated with chronic infection, usually occurs in the sclerotic temporal bone. The signs and symptoms are isidious in nature and consist of chronic discharge and hearing loss which result from its mass, bone erosion, and secondary infection. Of 17 consecutive cases of acute mastoiditis over a six-year period, four were atypical because they were complications of chronic otitis media and cholesteatoma, yet they had the physical findings of acute mastoiditis-subperiosteal abscess and purulent otorrhea, plus radiographic evidence of mastoid coalescence.


Audiometric and histologic correlates of the interaction between kanamycin and subtraumatic levels of noise in the chinchilla.

Difficulty in assessment of potentiating interaction between noise-induced and kanamycin-induced injury of hearing is compounded by the great variability of intersubject response to the same drug dosage. However, in a given subject, response of the two cochleas to kanamycin intoxication may resonably be assumed to be symmetric. The present study was designed to utilize this similarity, in determining whether kanamycin intoxication would potentiate a normally subtraumatic noise stimulus. Under the experimental conditions outlined, it was found that after a dosage of 150 mg/kg/day of kanamycin given to a physiologic end point, normally subtraumatic noise caused consistent increas in hearing loss.


Hemangiopericytoma of the nasal cavity.

Only 12 cases of nasal hemangiopericytoma have been reported in the literature. Ten additional cases are presented herein. Surgical excision is the recommended treatment; cryosurgery was used in one of our patients. Four of the tem patients had recurrences, one of which proved to be malignant (with distant metastases to the lung) and was ultimately fatal.


The tensor tympani, stapedius, and tensor veli palatini muscles--an electromyographic study.

Electromyographic recordings of the activity of the tensor veli palatini, tensor tympani, and stapedius muscles were obtained from several adult human subjects. Muscle responses were recorded under four stimulus conditions, ie, contralateral intense wide-band noise, air jet to the eye, swallow, and electrical stimulation of the tongue. The results indicated that the two tensor muscles responded to the same stimuli in similar patterns. The latter muscle differed from the response of the stapedius.


Soluble immune complexes in sera from head and neck cancer patients: a preliminary report.

With the recent demonstration of circulating immune complexes in a variety of malignant and nonmalignant diseases, we have examined the sera of head and neck cancer patients for evidence of soluble immune compleses. Using the Raji, cell test, we have shown that immune complexes are present in over 80% of the cancer sera examined as compared to less than 10% of normal control sera, and that these complexes persist following treatment of the patients by surgery or radiation therapy. These complexes may be acting as blocking factors which would account for the anergic state of these patients.


Basilar artery migraine presenting as fluctuating hearing loss and vertigo.

A review of the literature on basilar artery migraine as well as a brief overview of classic migraine is given. Diagnosis and management are also discussed as well as six case histories.


Local anesthesia in facial plastic surgery.

Although local anesthesia is ideal for cosmetic facial surgery, it must be prepared and administered with at least as much care and attention to detail as with general anesthesia. Relegating the responsibility to ancillary help in both hospital and office operating rooms adds to the legal jeopardy to which the surgeon is exposed. The choice and dosage of local anesthetics and safety measures to be followed in their usage are discussed.


Cochlear communication routes in the guinea pig--spiral ganglia and osseous spiral laminae: an electron microscope study using microsphere tracers.

The microscopic and ultrastructural anatomy of the spiral ganglia and osseous spiral laminae (OSL) of the guinea pig were studied using the transmission and scanning electron microscopes. The nerve and vascular elements within the spiral ganglia and OSL are surrounded by distinct perineural and perivascular spaces maintained by a loose meshwork of cells and connective tissue fibers. The connective tissue cells are fibers within the OSL and spiral ganglia are distinctly different from the arachnoid-like reticular cells and elastin fibers of the modiolus described in an earlier study. The present experiment demonstrates a pathway between the perineural spaces of the modiolus, spiral ganglia, and OSL. The perineural spaces of the modiolus were previously shown to communicate with the subarachnoid space; therefore, perineural communication from the cerebrospinal fluid to the perilymph via this route is likely. Using mircosphere tracers injected intrathecally, this communication route between the subarachnoid space and scala tympani was further defined. The tracer experiment suggests that the perineural spaces within the internal acoustic meatus, modiolus, spiral ganglia, and OSL are normally patent and do not represent artifacts induced during tissue processing.


Benign cervical cystic teratoma.

Teratomas of the neck are rare in adults. Nine adult patients have been previously reported on in the world literature; six had malignant and three had benign lesions. Most of the lesions were seen as a mass in the neck, but teratoma is rarely considered in the differential diagnosis of neck lesions. A tenth patient, whose case we are presenting, had a supraclavicular sinus mass that was diagnosed at surgical exploration. The tumor was successfully resected and proved to be benign.


Head and neck manifestations of relapsing polychondritis: review of 29 cases.

This review of 29 patients with relapsing polychondritis seen at the Mayo Clinic between 1962 and 1976 emphasizes the head and neck manifestations of the disease and the role of the otolaryngologist in its diagnosis and treatment. The major clinical features included inflammation of the pinna, eye involvement, nasal cartilage involvement, laryngotracheal involvement, arthropathy, hearing loss, costal chondritis, and fever. The erythrocyte sedimentation rate was often elevated, and mild anemia was not uncommon.


The otolaryngologic presentation of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a progressive dengenerative neuromuscular disease of insidious onset. It involves upper and lower motor neurons and causes both spastic and atrophic muscular symptoms. More than one fourth of patients have complaints relating to the head and neck (bulbar palsy); thus, the otolaryngologist may be the first physician to see them. Predominant symptoms are slurred speech, hoarseness, dysphagia, and dyspnea. Muscular weakness, atrophy, and fasciculation are noted on examination. The course is relentless, and only 20% of patients survive five years after diagnosis.


The use of reconstituted bovine collagen for tympanic membrane grafting.

Reconstituted bovine collagen is an incomplete protein; it will not support bacterial growth and causes minimal local reaction. It has been used in numerous experiments on animals throughout the phylogenetic scale. With these facts, tympanoplasty was performed on 63 persons. Five years of follow-up indicate acceptable tympanic membrane repair with eight failures.


The case for small fenestra stapedectomy.

Eight hundred stapedectomies were analyzed to evaluate the long-term results with four prostheses. It was concluded that limitation of fenestra size played a most important part in the outcome of stapedectomy, especially in regard to the preservation of high-frequency bone conduction response over prolonged periods. Other advantages deriving from small fenestra stapedectomy included significantly fewer fistulae and severe sensorineural losses.


The role of photoplethysmography in the prediction of the experimental flap survival.

A standard photoplethysmography, modified to differentiate between arterial and venous vasculature in skin tissue, has been used to measure arterial supply in 100 unipedicle skin flap in 25 pigs. A datum transform from a light intensity scale to a relative arterial blood density scale has been introduced and empirically labeled the vascular coefficient (VC). Statistical analysis of the VC data shows a significant difference between necrotic and surviving flap group mean data as early as 24 hours. Additional analysis in which a normal ogive was fitted to the sample VC data distributions suggests that statistically significant predictions of the probability of eventral flap necrosis can be made using VC measurements obtained immediately postoperatively. It is concluded that the modified photoplethysmograph, in conjunction with the VC data transform constitutes a usable measuring technique for skin flap viability prediction in the experimental animal.


Eustachian tube bypass: experimental evidence for total eustachian tube substitution.

Several preliminary reports have appeared in the medical literature in respect to eustachian tube substitution since Zollner first described his inability to open the obstructed eustachian tube. These procedures have the disadvantage that the distal end of the eustachian tube subsitute is inaccessible by other than another operation. This paper is follow-up report to our clinical experience. The purpose of the experiment was to determine whether the middle ear was ventilated by the tympano-oropharyngeal substitute eustachian tube and whether ascending infection occurred. Fourteen ears underwent eustachian tube substitution. The natrual eustachian tubes of these ears were obliterated three to five months after eustachian tube substitution had been performed. The animals were killed three to four months after obliteration of the natural eustachian tubes. Studies of the decalcified sections showed an absence of infection in six of the ears, with mild to severe inflammation in the rest of the specimens.


Airway intervention in croup and epiglottitis: the changing role of the otolaryngologist.

Recent evidence indicates that endotracheal intubation is supplanting tracheostomy for the short-term treatment of airway obstruction in epiglottitis and croup. Care should be provided by a triumvirate of physicians to include and otolaryngologist, a pediatrician, and an anesthesiologist. Intensive care facilities are also a prerequisite. Standard tracheostomy should be considered in cases requiring intubation longer than 72 hours.


The otolaryngologist and the hearing aid delivery system: current federal regulations.

New proposed rules and regulations concerning trade practices for the hearing aid industry have been developed in response to political pressures from Congress and consumer groups. Revisions to the trade regulations proposed by the Federal Trade Commission (FTC) include (1) more stringent limitations in advertising, (2) written permission to sell a hearing aid at home or in the buyer's place of business, and (3) the right of a buyer to cancel a hearing aid sale, rental, or lease within 30 days. Testimony on hearings regarding this rule are being reviewed by the FTC presiding officer. Food and Drug Administration national standards for the labeling and sale of hearing aids became effective Aug 15, 1977. A medical evaluation by a licensed physician is required before a hearing aid may be sold. Fully informed adults may request a waiver of this requirement for religious or personal beliefs, but a medical evaluation is mandatory for persons under 18 years of age. A User Instructional Brochure, which lists several conditions for which medical advice is advised, must be reviewed with the prospective buyer. In the recognition that some physicians may be dispensers of hearing aids, the Judicial Council of the American Medical Association has recommended that a physician may dispense hearing aids if it is in the best interest of the patient, but that a physician should not be encouraged to retail hearing aids in his office if other adequate community facilities exist.


Efficacy of cefazolin as a prophylactic antibiotic in head and neck surgery.

The rationale for use of perioperative shortterm prophylactic antibiotics in prevention of postoperative infection in major head and neck surgery was reviewed. Cefazolin and placebo were compared in 50 patients and results showed that short-term perioperative cefazolin was a useful adjunct in reduction of postoperative infection. Findings suggest perioperative antibiotics may be safely and effectively used to reduce postoperative morbidity from infection after surgical procedures in volving skin and mucosa of the upper aerodigestive tract.


Wegener's granulomatosis: presentation as an otologic problem.

Presentation of Wegener's granulomatosis as an otologic problem is unusual and leads to incorrect diagnosis and unsuccessful therapy. In seven years, five patients with a diagnosis of otitis media failed to respond to the usual therapeutic regimens. All had surgical manipulations on the middle ear or mastoid, or both. Wegener's granulomatosis was suspected because of persistence of the otologic problem. All patients developed pulmonary lesions and had positive diagnoses by biopsy of either the lung, kidney, or upper respiratory mucosa. Withe timely treatment, all patients have survived.


Head and neck manifestations of malignant osteopetrosis.

Malignant osteopetrosis is the autosomal recessive form of osteopetrosis. Besides anemia, hepatosplenomegaly, and the osteopetrotic bone seen on roentgenogram, the head and neck manifestations are important to the diagnosis and clinical course of this disease. Eye, ear, nose, face, teeth, mandible, maxilla, central nervous system structures, and cranial nerves are often involved.


Experimental studies on the role of vitamin A in the inner ear.

With the sole exception of the hair cells of the inner ear, where information is lacking, all special somatic afferent receptor cells have been shown to be dependent upon vitamin A for normal function. In view of the paucity of information on the role of vitamin A in the inner ear, three experiments were performed to examine this relationship. Temporal bone histopathology was studied in rats deprived of vitamin A. In a second experiment, vitamin A-deficient rats were maintained with vitamin A acid and the histopathology was studied under the light microscope. In the third experiment, a microfluorometric estimate of the content of vitamin A in the guinea pig cochlea was performed. A fluorescent compound with the exact spectral characteristics of vitamin A was found in the guinea pig cochlea at a concentration of 21.2 micrograms/gm, which is ten times the vitamin A concentration found in most other tissues.


Emerging characteristics of the acoustic reflex in infants.

One hundred ninety-nine infants (birth to 15 weeks) were administered an impedance battery to describe emerging characteristics of the acoustic reflex in this age range. Tympanometry results suggest that the middle ear system changes from a highly flaccid state at birth to a relatively normal compliance by 15 weeks. Acoustic reflexes were observed infrequently in the newborn population and gradually increased as a function of age, but never exceeding 43% of the ears tested. A conservative approach regarding the relevance of the presence of the reflex in young children is warranted.


Gram-negative germs infections in infancy.

The incidence of systemic or local infections due to gram-negative bacilli in an Infant Ward from September 1969 to December 1976 was 7.9%. The 29.34% were septicemia, most of them as epidemic outbreaks caused by Pseudomonas aeruginosa, Klebsiella-Enterobacter and Serratia marcescens. Two facts are to be emphasized: an almost complete disappearance of systemic infections with Pseudomonas starting from 1972, and the global predominance of the group Klebsiella-Enterobacter, particularly evident from 1970 to 1972.


Aspiration cytology for diagnosis of head and neck masses.

Most American clinicans have been relectant to utilize aspiration biopsy due to poor interpretive skills by the pathologists in the past and a fear of tumor spread by the needle. Voluminous European series and recent American series have proved aspiration to be safe and reliable. In our series of 78 cases, both thin-needle aspiration and conventional tissue biopsies were made. The diagnoses were compared and the overall agreement rate was 90%.


Dermal-fat-fascia grafts.

Free dermal-fat-fascia grafts are used for subdermal augmentation in soft tissue or bony deficiencies resulting from surgical extirpation of cancer, congenitally arrested development, and trauma. The most important determinant for graft survival is the health of the recipient area and the volume of the graft. At least 70% resorption of these large grafts must be anticipated. Imitial overcorrection has some justification but may be self-defeating. Calcification of dermal-fat-fascia grafts, common in other areas of the body, does not appear to be a problem in the head and neck region. When possible, other types of augmentation procedures should be considered.


Humero-spinal dysostosis.

A 2 year old boy with humero-spinal dysostosis is described. This is the third case of this disease reported in the literature. Humero-spinal dysostosis is characterised radiologically by distal humeral bifurcation, elbow subluxation and coronal cleft vertebrae. Congenital, progressive heart disease, possibly with fatal outcome, is probably part of the syndrome.


Nocturnal gastric drip feeding in glucose-6-phosphatase deficient children.

Six patients with glucose-6-phosphatase deficiency were treated for 12 hr at night with gastric drip feeding (GDF), containing soy milk plus glucose, dextrimaltose, and starch. An alarm system (thermistor), connected to the gastric tube, was devised in case of displacement of the tube by the child. The effects of GDF were as follows. Base deficit and lacticaciduria decreased, but did not normalize. Serum cholesterol levels tended to normalize, but serum triglycerides remained elevated. The hepatic and extrahepatic components of plasma lipoprotein lipase were measured separately 5 and 40 min after iv heparin injection. Hepatic triglyceride lipase activities which were subnormal to normal increased to the lower normal range. Extrahepatic lipoprotein lipase activities, though increasing after GDF, remained abnormally low. Catch-up growth occurred in all four growth-retarded children. The pronounced liver enlargement of the five patients, not previously treated with GDF, decreased markedly. Nocturnal GDF in glucose-6-phosphatase deficient children, suppresses the tendency for hypoglycemia and acidosis which are causes for stress, catabolism, and anorexia. By suppressing these factors, GDF promotes anabolism and caloric intake, thus accounting for the catch-up growth seen in the patients with growth retardation.


Arteriovenous malformation of the mandible.

A recent case of a vascular malvormation involving the mandible prompted the review of this subject. There are less than 80 cases of this rare but serious disease reported in the literature. There is no accepted standard treatment, but recent contributions have improved the safety and effectiveness of therapy.


Treatment of sudden hearing loss with diatrizoate meglumine (Hypaque).

Between March and November 1976, 30 patients with sudden hearing loss (SHL) were treated with vasodilators and diatrizoate meglumine (Hypaque). Nine (30%) of the patients had a good response, 7 (23%) had a moderate response, and 14 (47%) had no response to treatment. Most of the patients who responded were treated within the first month and had no vertigo associated on their onset of SHL. Their hearing loss was also less than 90 dB for any of the frequencies tested. Using the criteria of SHL of less than one month's duration, no vertigo associated with onset, and a loss less than 90 dB, seven patients were treated with vasodilator plus Hypaque during the period between January and August 1977. Six (86%) of the seven patients had return of serviceable hearing.


Thyrotropin-releasing hormone increases the amount of surfactant in lung lavage from fetal rabbits.

Administration of thyrotropin-releasing hormone (TRH) to pregnant rabbits at 25 and 26 days of gestation results in increased pulmonary surfactant production by the fetus at 27 days (full term is 31 days). There was 60% more total phospholipid and 150% more phosphatidylcholine (the major component of surfactant) in the lung lavage from the fetuses in the treated group than in that from the controls. Lung lavage from the fetuses in the treated litters contained 13.4 +/- 1.6 micrograms of total phospholipid phosphorus/g lung dry wt and 5.6 +/- 1.1 micrograms of phosphatidylcholine phosphorus while that from the fetuses in the control litters contained only 8.2 +/- 1.1 micrograms and 2.2 +/- 0.4 micrograms, respectively. The phosphatidylcholine/sphingomyelin ratio increased from 1.0 in the lavage from the controls to 2.2 in that from the treated group. These changes in lung lavage phospholipid content and composition are in the direction of increased lung maturation. TRH administration had no effect on the incorporation of choline into phosphatidylcholine in fetal lung slices. These data suggest that TRH stimulates surfactant release rather than synthesis. TRH has a physiologic role in fetal lung maturation and surfactant production. It may potentially be used in the prevention of the respiratory distress syndrome in humans.


Lung development in the fetal primate Macaca nemestrina. III. HMD.

Delivery of M. nemestrina at 80% of normal gestation provides a population of neonates at high risk for hyaline membrane disease (HMD). The diagnosis of HMD was made by the presence of reticulogranular densities and air bronchograms on chest radiographs. Patchy atelectasis was seen in the lungs of animals assigned by clinical and radiographic criteria to the HMD group and not in the normal lungs of animals matched for gestational and postnatal age. Total phospholipid and phosphatidylcholine in whole lung, airway lavage fluid, and surface-active materials were lower in animals with HMD. Amniotic fluid L/S ratios were lower in the group that developed HMD. Pressure-volume measurements indicated decreased distensibility and unstable terminal air spaces in the HMD group. Alveolar-arterial oxygen pressure differences were greater in animals with HMD. There were no differences between HMD and normal groups in body weight, lung weight, percent dry lung weight, gestational age, and postnatal age at death. This primate species, subjected to premature delivery, is a suitable animal model of HMD in human neonates.


Streptobacillary rat-bite fever: a pediatric problem.

A case of streptobacillary rat-bite fever in an 11-year-old boy from rural North Carolina is described. The child's clinical course was unique in that he developed a subglottic mass and bilateral parotid swelling. He responded initially to tetracycline but relapsed after therapy. Cure was ultimately achieved with a three-week course of penicillin. A review of the literature concerning this unusual clinical entity is presented.


Disease due to serogroup W135 Neisseria meningitidis.

Five cases of disseminated meningococcal disease due to serogroup W135 Neisseria meningitidis are presented. The cases ranged in age from 16 months to 23 years, and spanned a clinical spectrum from mild meningitis without rash or evidence of meningococcal septicemia to severe meningoencephalitis with fulminant meningococcemia, disseminated intravascular coagulation, and death. These cases demonstrate that serogroup W135 N meningitidis is fully pathogenic for man and capable of producing the full spectrum of disseminated meningococcal disease associated with other serogroups. Since this serogroup has recently emerged as a significant cause of disease in Europe, attention should be focused on the correct serogroup designation of strains of N meningitidis isolated from clinical material and reported as "nongroupable" by clinical laboratories, so that additional clinical and epidemiologic information may be obtained.


Meningococcal group Y pneumonia in an adolescent female.

Neisseria meningitidis group Y has been considered to be an uncommon pathogen. Meningococcal group Y disease has recently been reported with increased frequency in military training camps coincident with the routine use of meningococcal group C vaccine. Pneumonia produced by the group Y organism may mimic disease caused by common respiratory tract pathogens, and isolation by routine methods may be difficult. A 16-year-old asthmatic female developed lobar pneumonia secondary to N meningitidis group Y while on alternate day steroids. We speculate that neither steroid therapy nor an isolated serum IgA deficiency in the presence of secretory IgA discovered after her recovery predisposed her to sinopulmonary disease. The true incidence of group Y disease is unknown. Awareness of its potential pathogenicity may have clinical significance with the availability of a group Y vaccine.


[Fabry's disease: two patients improved by fetal liver cells (author's transl)].

The first patient reported was a 33 years old male with clinical manifestations of Fabry's disease. The diagnosis was confirmed by ophthalmologic, histological and enzymatic studies. Because of inefficacity of treatment with plasma transfusions and of symptomatic therapies, a transplant of cells with normal enzymatic activities was envisioned. In this patient without renal failure, a renal transplant was not justified and a transplant of fetal liver cells was decided. The improvement of extra-renal manifestations of the disease with this new treatment was comparable to that obtained with kidney transplantation. In particular, objective and subjective clinical symptoms were significantly improved: sweating appeared became normal, cutaneous lesions appeared slightly decreased and pains disappeared. This improvement was still persistent 3 years after the fetal liver transplant, the viability of which was initially followed using dosages of circulating alphafoetoprotein. The second case-report is comparable. Fabry's disease was diagnosed in a 26 years old male on the clinical manifestations, the histological lesions and the enzyme deficiency. After failure of one plasma transfusion, the patient received a fetal liver transplant. It is still too early to evaluate the efficacy of the transplant in this second case, especially as the patient had normal sweating and relatively few pains except at the cold season. The mechanism which may be held responsible for possible improvement in our patients, as in recipients of a kidney transplant, is not completely elucidated. The cells, rather than steroids or azathioprine, seemed to support the efficacy. Was the enzyme activity exerted in situ? Was there a "colonization" by lysosomial enzymes? From the results observed after several years will derive the significance of this therapeutic approach in Fabry's disease, more generally, in many diseases associated with a genetic enzyme deficiency.


[Consumption hypocomplementemia: comparative value of haemolytic and protein estimations of the components of the classical pathway (author's transl)].

Titrations of total complement (CH50) and of the different components of the classical pathway of the complement system in patients with supposed consumption hypocomplementemia, show that the complement depression involves in an order of decreasing severity hemolytic C4, hemolytic C2, total complement, hemolytic C1, protein C4 and protein C3. These results as well as correlative studies between these different parameters suggest that C4 is the most specific target of activited C1 esterase (C1s). They stress the interest of hemolytic titrations as well as the strong limitations of protein titrations.


[Hyperoctanoatemia and the hepatic encephalopathy of cirrhosis. 150 dosages in 61 patients (author's transl)].

A new and sensitive method for determination of octanoate in serum by gas-liquid chromatography is described. It was validated by mass spectrometry. Octanoate concentrations were determined in the serum of 61 fasting cirrhotic patients of which 47 also had hepatic encephalopathy. Concentrations in arterial and venous blood were higher in cirrhotic patients with encephalopathy than in those without and higher in the latter than in controls. Arterial concentrations were higher than venous concentrations and octanoate and ammonia varied independently. A predominant endogenous origin is likely. Data obtained from studies using palmitic acid labeled at different loci suggest that recovered serum octanoate was formed mostly by incomplete oxidation of long chain fatty acids. Sodium octanoate infusion to rhesus monkeys studied polygraphically induces a temporary coma.


[Inappropriate secretion of antiduiuretic hormone during acute leukaemia treated with vincristine. Two cases (author's transl)].

One the basis of two special typical cases, the authors detail the symptoms and signs and consider the physiopathology of inappropriate secretion of antidiuretic hormone related to vincristine. Urinary ADH was measured in both cases. ADH levels could be studied on ten consecutive occasions during the course of one of the cases (obs. n 1). Eleven similar cases have been found in the literature. ADH was measured in only three of them. Methods of treatment are considered, with particular emphasis on the role of demeclocycline.


Maintenance therapy of 32P-induced remission in polycythemia vera. A clinical trial of chlorambucil and hydroxy-urea in 109 cases.

In 109 patients with polycythemia vera, previously treated by 32P without maintenance therapy, a trial was carried out to determine the best way to reduce the number of injections needed. Chlorambucil and hydroxy-urea have been used to lengthnen the remission. Both of them are well tolerated and compatible with follow-up at reasonable time intervals. Chlorambucil maintenance increases the mean duration of remission by 12 months, the best results being observed when the drug was used continuously, instead of an intermittent (3 consecutive days every fortnight) schedule. Hydroxy-urea does not produce statistically demonstrable advantage whatever it is given, continuously or intermittently. Our study shows that, if a long-term cooperative study of the possible advantage of maintenance therapy in P.V. was undertaken in the future, low-dosage maintenance by chlorambucil could be the treatment of choice.


Seizures during lithium-amitriptyline therapy.

Epileptiform seizures occurred in a 34-year-old woman who was receiving amitriptyline and lithium carbonate therapy for treatment of endogenous depression. While receiving amitriptyline maintenance therapy, she was given lithium on two separate occasions, and despite serum levels of lithium in the therapeutic range, grand mal seizures developed. The seizures may represent a toxic reaction either to lithium or to combined drug therapy. Controlled studies are needed to evaluate both the efficacy and toxicity of combined drug therapy in affective disorders.


Purification of the protein employed in an immunodiffusion test to diagnose infectious bovine rhinotracheitis.

The antigen used in an immunodiffusion test to diagnose infectious bovine rhinotracheitis has been purified by affinity chromatography. The homogeneity of the antigen was indicated by sedimentation rate and sedimentation equilibrium experiments. A So20,w of 0.749 was determined and a molecular weight of 8900 was calculated from sedimentation equilibrium analysis. The purified antigen formed precipitin lines of identity with crude diagnostic antigen. Purified antigen remained serologically active in the immunodiffusion test after lyophilization and subsequent reconstitution.


Neutron dosimetry in high energy X-ray beams of medical accelerators.

High energy X-ray beams from medical accelerators are used in cancer therapy. In such beams, neutrons are also produced due to photon-neutron interactions in the target material, collimator and beam flattening filter. The feasibility of employing fast-neutron-induced recoil particle tracks in polycarbonate foils developed by the electrochemical etching (ECE) method for the dosimetry of such neutrons was investigated. The experiments were carried out in, and out of, the beam of a Varian Clinac-18, an Allis-Chalmers 25 MeV betatron and a Brown Boveri 45 MeV betatron. Neutron dose equivalents were found both as a function of the photon dose and of the distance away from the centre of the beam. The neutron dose equivalent was found to be 0.6 and 1.3% of the X-ray dose at the centre position of the beam for a TSD = 100 cm and a 10 x 10 cm2 field for the 25 and 45 MeV betatrons respectively. Although the dosemeter showed adequate sensitivity to neutrons in the beam of the betatrons, it showed insensitivity to neutrons in the beam of the Clinac-18 which has a softer spectrum than the neutron energy threshold of the dosemeter. It can be concluded that this dosimetry method provides a new approach with a number of advantages compared to some other existing techniques for such measurements above the energy threshold of the dosemeter.


Measurement of stopping power ratios for 60 MeV positive or negative pions.

Pion stopping power ratios are essential parameters for pion radiotherapy treatment planning. The validity of scaling proton stopping powers to pions is called into question since the pion mass is intermediate between the electron and proton masses. Direct measurements of stopping power ratios with respect to water were made for 60 MeV pions of both charges in Teflon, Plexiglas, nylon, paraffin, gelatine, tissue-equivalent plastic (Shonka A150), graphite, aluminium, steel and copper. Corrections for multiple scattering and energy dependence of the stopping power are applied. Measured stopping power ratios at an accuracy of 0.6% are in agreement to within the limits of experimental error with stopping power ratios calculated from the Bethe-Bloch equation using elemental I-values and Bragg additivity.


Some linguistic considerations related to the issue of female orgasm.

The purpose of this paper has been to identify a linguistic issue that continues to cloud our thinking about the subject of female orgasm. A specific technical revision has been recommended, i.e., that female orgasms be described as either coital or noncoital. It has been suggested that we help our female patients to become aware of this vocabulary and that we let them know that the clitoral/vaginal dichotomy is incorrect. Systematic adherence to the correct vocabulary is therapeutic. The linguistic implications concerning the issue of female orgasm have been examined as they relate to both theory and practice. It has been argued that linguistic usage pertaining to female sexuality generally is the product of a patriarchal value structure and, as such, reflects patriarchal prejudices about female sexuality. It has been suggested that the apparent inability of many women to achieve coital orgasms is related to centuries-old cultural attitudes and that linguistic usages, particularly dichotomies, tend to perpetuate the prejudices that underlie many cultural attitudes. Freud's view of the role of language in clinical practice has been indicated. Finally, it has been suggested that the linguistic recommendation made in this paper can be viewed as implementing the process by which recent biological findings are used to strengthen psychoanalytic theory and practice.


Amenorrhoea, body weight and serum hormone concentrations, with particular reference to prolactin and thyroid hormones in anorexia nervosa.

Twenty women with anorexia nervosa were investigated at varying stages during weight gain. Basal prolactin and TSH and prolactin responses to TRH were normal and unrelated to body weight. LH, FSH and 17 beta oestradiol were low in emaciated patients and rose with weight gain. There was no correlation between serum gonadotrophin and prolactin concentrations. T3 and T4 concentrations were low but T3 rose with weight gain during refeeding over 4-6 weeks, whereas T4 remained low. A positive correlation was found between the TSH response to TRH and body weight. The abnormalities in the hypothalamic-pituitary-thyroid axis were similar to those seen in a variety of chronic illnesses and appear to be unrelated to the amenorrhoea. The failure of restoration of normal function at least after short-term refeeding requires further investigation. It was concluded that the amenorrhoea in anorexia nervosa is not associated with changes in prolactin secretion but is determined primarily by changes in the hypothalamic-pituitary-gonadal axis. These changes are induced largely by nutritional factors but psychological factors may also be involved.


Effect of morphine on the brain histamine levels in stress-exposed rats.

The effect of morphine on brain histamine levels in stress-exposed rats was investigated. It seemed that the brain histamine level was not directly affected by stressors. However, morphine induced a sharp rise in the brain histamine levels in both morphine-treated and morphine-treated stressed groups. This effect of morphine was reversed by naloxone.


Acute effects of alcohol on saccadic eye movements.

Four components of 20 degrees horizontal saccadic eye movements, i.e., latency, mean and maximum velocities, and duration were measured in 16 students under the influence of alcohol and also in a control situation. The experimental procedures were standardized and automated as much as possible. Latency (simple eye reaction time) was not influenced by alcohol in blood concentrations of 0.056--0.116%. Mean and maximum eye velocities decreased by about 9% and duration of saccades increased by 11%. The maximum changes occurred 90--120 min after the start of alcohol ingestion. The changes in velocities and durations correlated more closely with feelings of intoxication than with blood alcohol concentrations. There were great intra- and intersubject variations in reactions to alcohol. The close resemblance between the effects of certain psychotropic drugs, alcohol, fatigue, and decreased attention on eye movement control suggest that all these may act upon the same nervous structures in the brain stem.


Postnatal orotate treatment: effects on learning and memory in adult rats.

During the postnatal period, male Wistar rats were treated with orotate, either from the 6th to 15th, 16th to 25th, or 26th to 35th day of life. Learning and memory were tested in adulthood. Rats that received orotate from the 6th to 15th day showed a better retention of a learned brightness discrimination (Y-maze) than controls. An active avoidance (pole jumping) was learned more quickly by the rats orotate-treated from the 6th to 15th day than by controls. The spontaneous locomotor activity of previously orotate-treated rats was the same as in controls. Body weight measurements revealed no differences between orotate rats and control rats. The results suggest that memory retention in adulthood can be improved by postnatal orotate treatment.


Effects of chlordiazepoxide on maze performance of rats subjected to undernutrition in early life.

The purpose of this research was to study the isolated effects of and interactions between undernutrition and emotional reactivity upon maze performance in rats. This work compares the effects of chlordiazepoxide on learning performance in two groups of adult rats: one undernourished early in life and then rehabilitated, and the other normally nourished. Chlordiazepoxide was used at 5 mg/kg body weight administered i.p. 30 min before each test. The response was evaluated in a Hebb-Williams maze. Water was used as reinforcement. Chlordiazepoxide improved performance in the early undernourished group 197 +/- 55.9 errors to 149 +/- 33.6 (mean +/- SD). Chlordiazepoxide impaired performance of the normal group from 107 +/- 22.7 errors to 197 +/- 42.2 errors. Analysis of variance gave an F = 6.64, which is significant (P less than 0.01). This supports the hypothesis that the high emotional level of previously undernourished subjects acts negatively upon problem-solving performance.


An improved method for detecting drug effects in the open field.

A double test cross-over design was applied to the testing of rats in the open field. When used to examine the effects of atropine, chlorpromazine and lysergic acid diethylamide (LSD) on open field behaviour, this design proved 4--40 times more sensitive than the previously popular single test design. In no case was the double test design less sensitive. Results are discussed in relation to screening of medically useful compounds.


Effect of lithium carbonate on memory processes of bipolar affectively ill patients.

The effect of long-term lithium carbonate treatment on parameters of immediate, short-, and long-term memory was examined in a group of bipolar affectively ill patients. The lithium treatment group recalled significantly fewer words across trials on a verbal learning task than a group of bipolar affectively ill patients receiving no medication. The ability to consistently recall material for which prior learning had been demonstrated was also decreased and accounted for most of the variance in total number of words recalled. Possible mechanisms of effect are discussed.


Effects of chronic d-amphetamine treatment on schedule-controlled behavior.

The effect of d-amphetamine added to the drinking water on the rate of conditioned lever pressing by rats was determined using fixed-ratio 30 (FR-30) and fixed-interval 2-min (FI-2) schedules of food presentation. After 32 days of gradual increase in drug concentration the average drug ingestion was 13 mg/kg/day. In tests with various doses of d-amphetamine injected before and after the chronic ingestion regimen, the rate-decreasing effects of d-amphetamine on FR responding were attenuated after chronic treatment, indicating development of a two- to three-fold tolerance. However, the rate-decreasing effect of d-amphetamine on FI responding was not altered by chronic ingestion. Since acute amphetamine treatment reduced the reinforcement frequency under the FR but not the FI schedule, these results are consistent with the hypothesis that a 'behavioral tolerance' will develop most readily to drug effects that decrease the frequency of reinforcement. Upon removal of d-amphetamine from the drinking water there was some increase in the rate of FR responding, but no change in FI responding.


Long-term nitrazepam treatment in psychiatric out-patients with insomnia.

Psychiatric patients (N = 26) were treated chronically (from 1 week to 12 years) with nitrazepam, because of insomnia. The patients gave their subjective estimations of the effects and side effects of nitrazepam. The concentrations of nitrazepam in the plasma were measured by 63Ni-EC-gas-liquid chromatography. The pharmacokinetics of nitrazepam were compared between the psychiatric patients and healthy volunteers (N = 11). The steady-state concentrations and the half-life of nitrazepam in the psychiatric patients were comparable to those of the healthy volunteers. The subjective hypnotic effect of nitrazepam was mostly good or satisfactory and remained unchanged during long-term treatment. Only a few, mild side effects were reported. Nitrazepam does not seem to cause enzyme induction with lowered plasma levels and may therefore be of special value in the treatment of chronic insomnia.


A possible intraneuronal site of action of thymoleptics.

The uptake of catecholamines (CAs) into crude mitochondria preparations (P2 fractions) and vesicle preparations from rat hypothalamus and striatum were compared in terms of the inhibition by thymoleptics and other drugs. Thymoleptics preferentially inhibited the uptake of CAs into hypothalamic P2 fractions, while ATPase inhibitors preferentially inhibited the uptake of dopamine into striatal P2 fractions. When the preparation obtained from rats pretreated with reserpine was used, the preferential inhibition of hypothalamic uptake by thymoleptics was entirely abolished. When P2 fractions from both regions were incubated with 10(-6) M 14C-imipramine, the intrasynaptosomal distribution of labeled imipramine revealed its affinity not only to the synaptosomal membrane, but also to the synaptic vesicles. Accumulated 3H-norepinephrine (NE) could be released by a hypoosomotic shock from striatal P2 fractions, but not from hypothalamic P2 fractions. The ATP-Mg2+-dependent uptake of 3H-NE into the synaptic vesicles from rat brain stem was inhibited by desipramine. These results indicate that the inhibition of CA uptake by thymoleptics in the hypothalamus is predominantly due to the inhibition at the synpatic vesicle, while in the striatum the uptake at the synaptosomal membrane is predominantly inhibited.


Effects of nicotine administration and its withdrawal on plasma corticosterone and brain 5-hydroxyindoles.

The effects of nicotine administration and its withdrawal on the levels of brain hydroxyindoles and plasma corticosterone have been studied in the rat. Daily injections of nicotine (0.4 mg/kg s.c.) rapidly induced tolerance to the increase in plasma corticosterone seen in response to acute nicotine. Withdrawal of the drug from chronically treated animals caused a significant increase in plasma corticosterone. Hippocampal 5-hydroxytryptamine (5-HT) was reduced in nicotine-treated rats, significantly so in those treated for more than 20 days. The 5-hydroxyindole acetic acid (5-HIAA) concentration in the hippocampus was also reduced by nicotine although this was not a consistent observation. Hypothalamic 5-hydroxyindoles were not affected by nicotine administration itself, but, if the drug was withdrawn, the concentration of 5-HT was increased after 5 days treatment. The changes in the hypothalamus and hippocampus appeared to be relatively specific since they differed from those seen in the rest of the brain. None of the effects could be related directly to changes in the plasma corticosterone concentration.


Actions and interactions of cocaine on self-stimulation behavior in rats.

The effect of cocaine, over a dose range of 2--60 mg/kg, i.p., on self-stimulation (SS) behavior was studied in rats with electrodes either in the posterior hypothalamus (PH, monoaminergic) or the area ventralis tegmentum (A10, dopaminergic). The drug increased SS behavior with peak effects at 30 mg/kg in PH rats and 20 mg/kg in A10 rats. Azaperone (an alpha-adrenergic blocker) and haloperidol (an antidopaminergic neuroleptic) given at doses that did not affect baseline SS responses reduced cocaine-induced enhancement of SS in both PH and A10 rats, showing the involvement of both noradrenergic and dopaminergic mechanisms in SS behavior. A scopolamine dose that itself facilitated SS responding enhanced the effect of cocaine on this behavior, thus suggesting an additional involvement of cholinergic mechanisms in cocaine effect.


Attenuating the rate-decreasing effects of phenylpiperidine analgesics by pentobarbital.

The ability of pentobarbital, diazepam, and chlorpromazine to attenuate the rate-decreasing effects of a high dose (10 or 30 mg/kg) of meperidine was tested in pigeons responding under a multiple fixed-ratio, fixed-interval schedule of food presentation. Pentobarbital (10 mg/kg) attenuated the meperidine-induced rate decreases, whereas diazepam (0.3--3 mg/kg) or chlorpromazine (3--30 mg/kg) did not reliably attenuate the response rate decreases. The combination of 10 mg/kg of pentobarbital and meperidine resulted in a marked disruption of the pattern of responding in the fixed-interval component of the multiple schedule. Pentobarbital (1, 3, 10, and 17.5 mg/kg) was also tested in combination with rate-decreasing doses of normeperidine (17.5 mg/kg), anileridine (10 mg/kg), alphaprodine (10 mg/kg), and fentanyl (0.3 mg/kg). Pentobarbital reliably attenuated the rate-decreasing effects of normeperidine, anileridine, and alphaprodine, but not the rate decreases induced by fentanyl.


Methadone-induced changes in the visual evoked response recorded from multiple sites in the cat brain.

Visual evoked responses (VERs) and EEG were recorded following the i.p. administration of five doses of methadone (0.5--4 mg/kg) to 12 adult cats, which were implanted with cortical and subcortical electrodes. Additional cats, subjected to the same drug regimen, were used to evaluate plasma methadone concentrations. Doses of methadone that produced plasma concentrations between 80 and 190 ng/ml differentially affected VERs recorded from cortical and subcortical sites. Of the subcortical structures evaluated, the limbic system, specifically the hippocampus, was the most sensitive to the effects of the drug. These effects appeared to be primarily depressant. Responses recorded from the reticular formation and centromedian were affected only by the highest dose of methadone, while VERs recorded from cortical sites were reliably altered following the two highest doses and appeared to reflect both excitation and depression. Behavioral changes, however, were clearly evidenced in some cats at lower doses of methadone. Therefore, the data suggest (1) that those structures evaluated electrophysiologically did not reflect the full force of the drug's action as evidenced by its effect on behavior, (2) that cortical and subcortical recording sites have differential sensitivities, and (3) that one clearly defined, principal size of action of methadone is absent in the cat.


Action of psychoactive drugs on sex-related differences of OF1 mice; intraspecific aggressiveness and acute hypoxia survival.

The purpose of this study was to examine (1) whether there were a relationship between the sex-related differences in 51-day-old OF1 mice, regarding male aggressiveness and their sensitivity to an acute hypoxic (nitrogen) 50% lethal challenge, and (2) whether these sex-related differences could be modified by psychoactive drugs acutely injected at nonincapacitating doses. The introduction of a previously isolated male in grouped (10) mice decreased survival to the hypoxic challenge more in females than in males. The previously isolated male, which acted as an 'aggressor' with grouped mice (fights and flights in male groups, and mounts in female groups), had a higher hypoxic mortality than the mice of the groups under aggression. Psychoactive drugs were intraperitoneally injected in grouped mice before the introduction of the male aggressor. Clorazepate (5 and 25 mg/kg) abolished the sex-related difference in hypoxic survival in groups in the presence of, but not in the absence of, the previously isolated male. Conversely, hydroxyzine (5 mg/kg) and dexamphetamine (1 mg/kg) suppressed the sex-related difference only in the absence of the aggressor. The effects of these drugs appeared to be associated more with flight than with fight reactions provoked by the introduction of the male aggressor. A deep hypothermia was noted in clorazepate-treated mice at the issue of the hypoxic challenge.


Inhibition of 5-hydroxytryptamine reuptake by amitryptyline an zimelidine and its relationship to their therapeutic action.

Amitriptyline and zimelidine significantly reduce the uptake of 5-HT into the blood platelets of depressive patients. The degree of inhibition is significantly correlated with the plasma drug level of amitriptyline. No significant relationship could be detected between the degree of inhibition of uptake and therapeutic outcome. The accepted mode of action of tricyclic antidepressant drugs and the deficiency hypotheses of affective disorders are discussed.


Dimethylaminoethanol (deanol): effect on apomorphine-induced stereotypy and an animal model of tardive dyskinesia.

Dimethylaminoethanol (DMAE) was administered acutely to rats subsequently injected with spomorphine. A dose of 80 mg of DMAE had no effect on the severity of apomorphine-induced stereotypy. However, 160 mg of DMAE significantly diminished the severity of apomorphine-induced stereotypy. This dose of DMAE did not significantly alter spontaneous locomotor activity. DMAE did not reduced apomorphine-induced stereotypy in animals previously exposed to haloperidol and presumed to have postsynaptic dopamine receptor supersensitivity. These results with DMAE are contrasted with the effects of choline chloride, and suggest that choline chloride may be more effective than DMAE at augmenting striatal cholinergic activity.


Lithium administration antagonizes cholinergic behavioral effects in rodents.

Physostigmine, a centrally acting cholinesterase inhibitor, antagonizes methylphenidate-induced stereotyped gnawing behavior in mice and rats. This effect is significantly attenuated when lithium chloride is concurrently administered, indicating that lithium chloride may antagonize central cholinergic activity. This observation may have theoretical implications for an adrenergic-cholinergic balance hypothesis of affective disorders.


Rats bred for ethanol sensitivity: impairment of swimming by ethanol and pentobarbital.

Rats selectively bred for disparate degrees of ethanol-induced depression of spontaneous locomotor activity ('most affected' = MA; 'least affected' = LA) were trained on a swim task. Undrugged rats of the MA line swam significantly faster than rats of the LA line. Ethanol, 0.0--2.25 g/kg i.p., produced dose-dependent increases in swim time in rats of the 13 generation (F13). Averaged over trials, these increases were greater in LA than in MA rats and greater in males than in females, but there was no sex difference in peak impairment. Increases in swin time were uncorrelated with predrug performance. These findings were confirmed in younger F17 rats receiving 1.75 g EtOH/kg i.p. Although the lines differed in ethanol-induced impairment, F17 males of the two lines were not differentially impaired by pentobarbital (12.5--22.5 mg/kg, i.p.). The existence of task-dependent line differences in ethanol sensitivity emphasizes the nonunitary nature of ethanol-induced 'behavioral depression.'


Interaction between delta 9-tetrahydrocannabinol and morphine on the motor activity of mice.

The present experiments dealt the effects of delta 9-tetrahydrocannabinol (THC) on the locomotor activity stimulating action of morphine in mice. In the first series of experiments, the pretreatments of mice by THC in doses up to 20 mg/kg have been found to potentiate the morphine-induced hyperactivity in dose-dependent manner, but higher doses of THC did not produce such an action. In the second series of experiments the dose-response curve of morphine for the motor activity has been found to shift to the left by the pretreatment of mice with 10 mg/kg of THC. These results show a synergism between morphine and THC and suggest that both drugs may share some common site of action.


Effect of an inhibitor of dopamin-beta-hydroxylase on the acquistion and retention of four different avoidance tasks in mice.

The effect of [bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulfide] (FLA-63) (40 mg/kg, i.p.) on acquisition and retention in four different avoidance tasks was evaluated in mice. In all tasks animals were submitted to a training session on one day and to a retest session 24 h later. The drug or its vehicle were given either 2 h prior to training and/or retest (pretrial treatments) or immediately after the end of the training session (posttrial treatments). Two hours after injection, FLA-63 was found to lower brain norepinephrine (NE) levels by 51% without affecting those of dopamine (DA). Pretrial administration of the drug resulted in poorer performance of step-through and step-down passive avoidance as well as of step-up active avoidance in retest sessions. There was no apparent posttrial effect of the drug nor any effect on acquisition in these tasks. The drug was without influence on either acquisition or retention in an any-way passive avoidance task in which the response required from the animals was immobility. No evidence for state-dependent learning was detected in any of the tasks. The data are consistent with the hypothesis of an involvement of NE either in memory processes or in events parallel and related to memory processes. The present results rule out, however, several such possible parallel events (effects on acquisition, motor disturbances, and effects on reactivity to shocks).