Predictive criteria for length of nasogastric tube insertion for tube feeding.

This study was aimed at identifying non-invasive techniques and criteria for predicting the proper length for insertion of a nasogastric tube for tube feeding so that the tube tip would be located in the fundus or body for the stomach. A review of literature and existing practices revealed unsubstantiated and discrepant methods currently in use and justified the need for this research. The study involved relating several external body measurements to a measurement from the tip of the nose to the lower esophageal sphincter, via the esophagus, in 99 adult cadavers and 5 normal adult volunteers. A variety of analyses including stepwise multiple regression, were used and are presented. A formula is presented and is stated to provide a 91% confidence level of tube tip placement in the stomach between 1 and 10 cm. This is compared to a confidence level of 72% using the traditional nose to ear to xiphoid measurement. The formula is ( (NEX-50cm) /2)) + 50cm where NEX is the distance from the tip of the nose to the earlobe to the xiphoid. Two methods for simple mechanical clinical application are described.


Effect of calorie overload on puppy livers during parenteral nutrition.

To investigate the possible cause of hepatomegaly during TPN, chemical analyses were performed on the livers of puppies weighing around 2 kg, supported by TPN for 1 wk, under 3 different calorie levels: Group I (5) under 135 cal/kg as standard calorie, Group 2 (6) fed ad libitum with dog food, Group 3 (5) received TPN for 7 days at 135 cal/kg/day, Group 4 (5) TPN at 200 cal/kg/day, and Group 5 (5) at 270 cal/kg/day. The livers of puppies starved for 24 hrs and orally fed were studied as controls. 1) remarkable hepatomegaly with anemic discoloration and rise in sGOT, sGPT, and Alpase were the constant findings in G-2 and G-3.2). Liver weight in starved, fed G-1, G-2, and G-3 were 66.0 +/- 7.5g, 82.8 +/- 18.5g, 108.32 +/- 21.36g and 247.06 +/- 17.83g, respectively. 3) Glycogen and water contents in the livers were: in starved 0.17 +/- 0.07g and 48.75 +/- 5.75 ml, in fed 5.37 +/- 3.24g and 60.72 +/- 13.71 ml, in G-1 10.35 +/- 4.87g and 79.4 +/- 16.84 ml, in G-2 45.05 +/- 7.41G and 173.31 +/- 21.26 ml, and in G-3 45.19 +/- 20.47g and 178.45 +/- 56.63 ml, indicating that the weight increment can be explained by the increase in glycogen and water deposit in the liver. 4) Triglyceride in livers in G-2 and G-3 increased by 2 times the controls. These results suggest the possibility of the occurrence of hepatomegaly with glycogen and water accumulation accompanying the rise in serum enzyme by calorie overload in clinical TPN.


Nitrogen balance and electrolyte requirements in intralipid-based hyperalimentation.

The present study was directed at determining whether or not a relatively low-calorie regimen in which 40 to 50% of the calories are provided as fat will produce positive nitrogen balance in most patients, and at establishing the electrolyte requirements for such a regimen. Clearly, the recommended regimen is successful in promoting nitrogen balance and provides adequate electrolytes. Further experience will be necessary to determine the place of intravenous fat emulsions in the clinical practice of total parenteral nutrition.


Serum zinc concentrations: contamination from laboratory equipment.

The following experiment was designed because of high serum zinc reported in patients who were reciving total parenteral nutrition (TPN) concentrations. Blood samples were collected, divided into 3 containers: a clean glass control test tube, a vacuum collecting tube with a rubber stopper, and paraffin clot activator. It was found that compared to glass control tubes, vacuum collection with rubber stoppers contributed an average of 76 +/- 14 microgram/dl of zinc as contaminants. Moreover, tubes with a rubber stopper and clot activator contributed 198 +/- 42 microgram/dl of zinc as contaminants. It is concluded that care must be used to avoid trace element contaminants when plasma zinc concentrations are analyzed. Without proper methodology, including selection of the container in which the sample is taken, erroneous results will be reported.


Central vein thrombophlebitis associated with a permanent silastic central catheter.

The use of silastic catheters for total parenteral nutrition has greatly expanded. Their decided advantages of flexibility and minimal thrombogenicity favor their use in the long-term nutritional support. This case report details the development of central vein thrombophlebitis associated with an indwelling central silastic catheter. This uncommon hazard of central venous catheterization is not eliminated by the use of silastic catheters.


Changes in body weight and body protein with intravenous nutrition.

Body weight, protein, fat and water were measured before and after intravenous nutrition in 20 surgical patients. The group included both young and old patients who were suffering from a wide variety of catabolic illnesses and the period of intravenous feeding ranged from 11 to 40 days. Eight of the patients were able to take small amounts of food orally. During the period of intravenous nutrition ten patients gained significant weight although only two of these gained significant protein. Most of the weight gain was due to an increase of water. There was also a gain of water in the patients who lost weight; this water gain occurred in small daily increments over the course of treatment. It is concluded that weight gain can occur without protein gain in patients who are being fed intravenously and that body weight is not a reliable guide to changes in body protein or fat in critically ill patients receiving intravenous nutrition.


Partial parenteral nutrition in preterm and newborn infants during the first three days of life.

Eight preterm infants, five with postnatal asphyxia, as well as two hypotrophic neonates and one term infant with severe postnatal asphyxia (mean birth weight 2300 g) were fed, in addition to oral nutrition, partially parenterally with glucose solution and mother's-milk-adapted amino acid solution during their first three days of life. By increasing protein supplies with a parenteral share of more than 50% during the three days, the nitrogen balances were positive on all days, although the calories supplied were far below the postulated optimum. On days 2 and 3, nitrogen retention was about 60% of the supply. Every 4 hrs after discontinuation of the 16 hr amino acid infusion, the amino acid levels in the plasma were examined by column chromatography. The resulting mean values did not show any imbalances of amino acid homeostasis. The maximum mean loss in weight of the present groups was 4% of the birth weight during the first 10 days of life and thus equalled the loss in weight of normal healthy preterms. Clinical and chemical parameters did not reveal any disadvantageous side effects of partial parenteral nutrition.


Failure of short-term nutritional convalescence to reverse the adverse hemodynamic effects of protein-calorie malnutrition in dogs.

We previously reported that protein-calorie malnutrition (PCM) exerts adverse hemodynamic effects on left ventricular (LV) structure and function. In the present experiments, we tried to determine the duration of these adverse effects by inducing significant weight loss in matched beagle dogs followed by a short-term course of nutritional repletion. Following restitution of initial body weight, the animals were placed on total cardiopulmonary bypass and an isovolumetric LV preparation was established to determine baseline LV function compared with matched animals that remained normally-nourished, and with a third group in which the effects of PCM were not reversed. Decreases in LV compliance persisted following refeeding as did the decreases in the first derivative of LV pressure (LV dp/dt). Although animals re-fed ordinary diets following acute weight loss restored normal concentrations of myocardial glycogen, cardiac abnormalities persited for more than one month following refeeding. These results suggest that the adverse effects of semistarvation on LV functions cannot be completely reversed by short-term refeeding.


Selenium and total parenteral nutrition.

Despite the increasing recognition of selenium (Se) as an essential trace element in man, little is known about its metabolism during total parenteral nutrition (TPN) and the possible development of Se deficiency in high risk patients. From a general population known by its geographical location to have low Se blood levels, we studied a group of 23 surgical patients receiving TPN for at least one week. Whole blood Se levels were less than in the normal general population and, being some of the lowest observed in adult man, approached levels observed in animals with Se-responsive syndromes. Se continued to be lost predominantly in the urine although the Se content of the TPN fluids was very low (less than 0.6 micrograms/24 hr). Patients with excessive volumes of gastrointestinal excretion lost more Se. Se supplementation may be required in some patients receiving TPN.


Parenteral nutrition in patients with leukemia and non-Hodgkin malignant lymphoma under chemotherapy.

Because of a high incidence of weight loss and amyotrophy in patients with hematologic malignant diseases during induction therapy, an analysis of the metabolism of proteins was made in 14 patients, some of whom were receiving parenteral nutrition. Proteins, fibrinogen, amino acids in blood, and nitrogen and amino acids in urine showed hypercatabolism with a very negative nitrogen balance. This disorder is associated with a significant decrease in proteinemia and fibrinemia, which returns to normal during complete remission and in spite of continuation of the same chemotherapy. Total parenteral nutrition does not influence these metabolic disorders during this period. In 2 patients who received total parenteral hypernutrition (TPHN) that provided more calories and more nitrogen (4800 cal and 25 g nitrogen), nitrogen balance tended to zero despite high urinary nitrogen excretion; proteinemia and albuminemia remained normal. Here, TPHN was well tolerated, induced a compensatory hypercatabolism with a high quantity of calories and nitrogen and, thus, decreased morbidity risks during induction treatment by correcting the metabolic disorders; also, tolerance to chemotherapy was considerably improved.


Urinary excretion of 3-methylhistidine in patients receiving parenteral nutrition.

In an attempt to investigate the kinetics of the muscle protein during parenteral nutrition (PN) and surgical stress, the urinary output of 3-methylhistidine (3-Mehis) was measured in patients receiving PN, then the validity of urinary 3-Mehis excretion as an index for the patient's status of protein nutrition was examined. The amounts of 3-Mehis excreted in 24 hr urine in the 19 healthy males and 10 healthy females were 74.8 +/- 17.1 mg/day and 46.3 +/- 12.4 mg/day, respectively. The changes of daily urinary 3-Mehis output in 6 cases receiving PN for more than 4 weeks were also examined. The average urinary 3-Mehis excretion increased gradually during the course of PN, and by the third week was nearly twice as high as the level before PN. In a further study the influence of surgery upon the urinary excretion of 3-Mehis was examined in 9 patients. Finally, a comparison was made of the nutritional status before and 4 wks after PN in the 6 patients without surgical stress. Urinary 3-Mehis was found to be a good index of both the status of protein nutrition and the fluctuation of muscle protein catabolism.


Sphingomyelin storage in a patient with myoclonus epilepsy as a main clinical symptom -- a varient in Niemann-Pick disease type C.

A patient with myoclonus epilepsy as a main clinical symptom was histopathologically diagnosed as a generalized sphingolipidosis. It was found that both sphingomyelin and globoside I fairly increased in kidney, heart, lung and liver. While, only sphingomyelin was found to increase in cerebral gray and white matters and cerebellum, but other lipids were within the normal range. Sphingomyelin accounted for 22% of the total phospholipids especially in cerebellum. No cholesterol ester and ganglioside GM2 or asialo GM2 were in particular found in the brain. Fatty acid compositions of phospholipids, glycosphingolipids and gangliosides were found to be normal. Judging from the sphingomyelin storage not only in visceral organs but also in brain tissues, it was proposed that this disease might be a variant in Niemann-Pick disease Type C, although an enzymatic assay of sphingomyelinase still remains.


Preclinical pharmacology of saralasin.

Saralasin is a highly soluble and stable AII antagonist with a relatively short half-life; therefore, its effects are rapidly reversible when administered i.v. Acute and subacute studies have shown only transient toxicosis with no significant pathology or teratology. Saralasin's angiotensin receptor affinity has been correlated with its biologic acitivity. Observations from the pharmacodynamic investigations have shown that saralasin is a specific competitive antagonist of the vascular, renal, adrenal, cardiac, and central nervous system actions of AII. In addition, these studies further support the utility of saralasin as a diagnostic and therapeutic agent for patients whose hypertension is due directly to AII.


[Indications for antibiotic long term treatment of chronic and recurring bronchitis].

The formerly used long-term therapy with antibiotics in chronic bronchitis in adulthood has been nearly completely replaced by an intermittent treatment of the single attack. Therefore it seems necessary to check the appropriateness and the indications for an antibiotic long-term therapy in childhood. In the light of the greater importance of viral and bacteriological infections of the airways in children and in the light of the frequency of confirmed malformations of the tracheobronchial tree the further appropriateness for an antibiotic long-term therapy after a thorough bronchological examination is established. Also firstly established bronchiectases or severe cases of deforming bronchitis initially mostly require such a long-term treatment. Among the cases of a specialized dispensary care for chronic and recurrent bronchopulmonary diseases such an antibiotic long-term therapy is indicated in nearly 8 to 10 per cent of all patients.


[Electroophthalmological characteristics in ischemic retinopathy (author's transl)].

In the ERG the b-wave and the oscillatory potentials are reduced or nonrecordable in ischemic retinopathy. The photopic b-wave appeared to be more sensitive than the scotopic b-wave. In the EOG the slow oscillation is reduced. These clinical observations are in accordance with the results of experimental studies in rhesus monkeys.


[An epidemic of pseudomonas keratitis due to permanent-wear contact lenses (author's transl)].

In 1977 thirty-three patients (35 eyes) with permanent-wear contact lenses presented with keratitis in varying degrees of severity. Among the nine cases investigated bacteriologically (including some contact lenses) three showed no organisms, while six were found to have pseudomonas aeruginosa. The contact lenses all came from the same optician, where shortly beforehand the patients had had their lenses either replaced or checked. The inspection of the optical establishment revealed faultless application of steril technique. Nevertheless it must be assumed that contamination of the lenses had had occurred there.


Ultrastructure of normal monkey liver.

The normal ultrastructure of the liver of rhesus and cynomolgus monkeys is described. A classification of type A and B periportal hepatocytes is introduced together with a discussion of the high incidence of mitochondrial abnormalities. It is suggested that the rhesus monkey is more suitable as an experimental model than the cynomolgus since its liver ultrastructure is less variable.


'Collaborative' rearing of marmoset triplets.

A system of management is described in which all 3 offspring from triplet births to Callithrix jacchus can be successfully reared to weaning. Hand-rearing techniques are applied to the offspring in turn without depriving them of the maternal and family influences necessary for normal behavioural development.


Bacterial growth in ampholytic disinfectant solutions.

Large numbers of live bacteria were isolated from solutions of 2 ampholytic disinfectants supplied from a built-in predosing system. They were resistant to and proliferated in these disinfectants. Bacteria were eradicated by employing a 3rd type of ampholytic disinfectant in the system.


Dietary habits relating to 'wasting marmoset syndrome' (WMS).

The syndrome is a condition of poor weight gain and weakness. Changed eating habits of animals suffering from it lead to consumption of a poorly-balanced diet. By softening the diet and avoiding less nutritious foods, the eating habits can be improved and the syndrome halted. Particular attention should be paid to the palatibility of high-protein foods when weaning marmosets.


Short-term effects of aflatoxin B1 on serum lipids in subhuman primates.

Aflatoxin B1 significantly depressed serum lipid levels in specimens of Cercopithecus aethiops, Cercopithecus mona, Erythrocebus patas and Papio anubis. Serum cholesterol, total phospholipids and total lipids were not affected to the same extent.


Ultrastructure of rhesus monkey renomedullary interstitial cells.

The fine structure of rhesus monkey renomedullary interstitial cells was studied by electron microscopy. These stellate cells contained variable numbers of lipid droplets, moderate numbers of mitochondria, moderate amounts of rough endoplasmic reticulum, and prominent Golgi zones. In rare instances, apparent release of lipid droplets into the interstitium was observed. The most prominent feature of the interstitial cells was larger nuclear pseudoinclusions which were observed in a high proportion of the animals examined.


Normal values for some whole blood and serum components of grivet monkeys (Cercopithecus aethiops).

Normal values for a number of blood components of grivet monkeys are reported. Haematological data and values for glucose, cholesterol and urea are similar to those of rhesus monkeys. Activities of alkaline phosphatase (1526 U/l), glutamine oxaloacetate transaminase (30.9 U/l), glutamine pyruvate transaminase (13.7 U/l), lactate dehydrogenase (629 U/l), alpha-hydroxybutyrate dehydrogenase (175 U/l), creatine phosphokinase (227 U/l), gamma-glutamyl transpeptidase (38.7 U/l) and sorbitol dehydrogenase (14.2 U/l), and levels of lysozyme (178 mg/dl), zinc (162 microgram/dl), copper (81.3 microgram/dl) and iron (296.5 microgram/dl) have not previously been reported for this animal. Values for serum amino acids, proteins, electrolytes, triglycerides and creatinine are compared with those of other primates.


Primary malignant melanoma of the esophagus: report of two cases.

Two cases of primary esophageal malignant melanoma diagnosed at the Columbia-Presbyterian Medical Center are reported. One patient who received 3800 rads and had subsequent surgery lived for 18 months. The other had surgery and subsequent chemotherapy and is still alive three years later. Forty other cases reported in the literature are briefly analyzed.


Randomized study of local control and survival following radical surgery or radiation therapy in oral and laryngeal carcinomas.

From 1971 to 1975, 100 patients with glottic, supraglottic, and oral cavity lesions were prospectively randomized between primary radiation treatment and primary surgery. Local control and survival were similar with either treatment for lesions of the oral cavity or supraglottic larynx. Comparison between radiation alone and surgery alone for T1 and T2 glottic laryngeal lesions showed local control rates of 76% and 100% (P=0.32); after secondary salvage attempts, local control rates were 82% and 100%, respectively (P= 0.52). Neither result approached statistical significance. Successful radiation for early glottic larynx lesions resulted in superior deglutition and equivalent voice function compared to successful primary treatment with conservation laryngectomy. For oral cavity lesions, swallowing was impaired in the same percentage of radiated and operated patients, but fewer primary radiation patients had articulation difficulties. Among the patients with supraglottic larynx lesions, aspiration was not a problem with either radiation or surgery, but successful radiation perhaps maintained a slightly better voice quality.


Randomized study of control of the primary tumor and survival using preoperative radiation, radiation alone, or surgery alone in head and neck carcinomas.

Fifty-five selected patients with previously untreated squamous cell carcinoma of the head and neck regions were studied in a randomized, prospective manner. The three treatment categories were primary radiation (Gp R), primary surgery (Gp S), and preoperative radiation of 4000 rads in four weeks (Gp R/S). The local control rates for the 44 evaluable patients with a two-year minimum followup were 24%, 39%, and 43% respectively. Further treatment attempts in patients failing initial therapy yielded local control rates of 35%, 39%, and 43% for Gp R, Gp S, and Gp R/S, respectively. None of the local control rates nor the corresponding survival curves were significantly different at P less than 0.10. However, the group sizes were sufficiently small that true differences might not have been detected. Postoperative complications were higher in the primary radiation failures subsequently operated upon compared to the primary surgery group (P = 0.07).


Right atrial ball-valve thrombus: a complication of central venous alimentation in an infant. Diagnosis and successful surgical management of a case.

The following is a case report of a 6-week-old premature infant in whom a ball-valve thrombus developed after prolonged central venous alimentation. Clinical presentation included facial edema, cyanotic episodes, and apnea. No murmur was present, but the diagnosis was suspected when a calcified right atrial mass became apparent on the plain chest film. The diagnosis was confirmed by echocardiography and then venous and cardiac angiography. The calcified thrombus was removed successfully from the right atrium by use of profound hypothermia with ether anesthesia and total circulatory arrest. Subsequently, the patient made an uneventful recovery and is healthy 3 years postoperatively.


Variant angina. Clinical spectrum and results of medical and surgical therapy.

Fifty-four patients with variant angina are described. They are divided into patients without hemodynamically (less than 50%) important coronary artery lesions (Group 1), patients with intermediate (greater than or equal to 50% and less than 90%) fixed obstruction (Group 2A), and patients with high grade (greater than or equal to 90%) fixed obstruction (Group 2B). Inferior ischemia occurred significantly more often in Group 1 (90% versus 33%. p less than 0.001), and exertional angina was more frequent in Group 2 (70% versus 36%, p less than 0.05). Maximum medical therapy with propranolol and nitrates failed to control angina in 55% of Group 1, 69% of Group 2A, and 63% of Group 2B. Twelve patients underwent intra-aortic balloon pumping (IABP), and in 10 there was complete control of variant angina. A total of 35 Group I patients underwent coronary artery bypass grafting (CABG), with a 2.9% mortality rate in patients without preoperative cardiogenic shock. Of these patients, 55% in Group 2A and 73% in Group 2B experienced marked improvement in their angina status. Therefore, we currently recommend bypass grafting for medically intractable variant angina in those patients with severely stenotic, fixed atherosclerotic lesions.


Comparing the medical utilization and expenditures of low income health plan enrollees with Medicaid recipients and with low income enrollees having Medicaid eligibility.

The study examines the medical care (hospital, physician, drug, diagnostic) utilization and expenditures of low income persons enrolled in a prepaid health plan with a matched group of Medicaid recipients. The study also examines the medical care utilization of low income persons enrolled in a prepaid health plan with a similar group of low income persons enrolled in the health plan but also eligible for Medicaid benefits. Utilization and population-at-risk data were obtained from the Kaiser-Permanente Medical Care Program of Portland, Oregon and from the State of Oregon Welfare Division. A hypothesis of lower hospital utilization by low income enrollees compared with Medicaid recipients was accepted. A hypothesis of higher ambulatory care utilization was accepted for diagnostic procedures and prescription use, but rejected for office visit utilization. An analysis of the findings appeared to implicate the Medicaid program for differences observed. The hypotheses of no significant differences in inpatient and ambulatory medical care utilization of low income health plan enrollees with and without Medicaid eligibility were generally rejected. Low income enrollees with concurrent Medicaid had consistently higher utilization rates for all services resulting in substantially higher medical care expenditures per person. The findings appear to contribute some useful information to planning or establishing policy for Medicaid Prepayment programs or other programs enrolling low income persons in prepaid health plans or HMOs.


[Calorie requirement after major abdominal surgery (author's transl)].

After major abdominal surgery 32 patients received a parenteral nutrition for 6 days with 360 g of a carbohydrate mixture (levulose:glucose:xylitol = 2:1:1) and 100 g of an L-amino acid mixture/24 h. 16 patients with benign disease showed positive nitrogen balances, 16 patients with malignant diseases balanced or slightly negative nitrogen balances. Postoperatively, blood glucose levels did not require insulin. Less than 1.5% of the infused levulose, 2.0% of glucose and 2.4-4.1% of xylitol were found in urine. C3- and C4- complement levels in serum were below normal, transferrin showed a pathological decrease in carcinoma patients.


Heat shock induced phenocopies of dominant mutants of the bithorax complex in Drosophila melanogaster.

Heat shock of 37 degrees C applied to Drosophila embryos at blastoderm stage induces phenocopies of some dominant mutants of the bithorax complex. Heat shock might shut down functions of cis regulator genes involved in embryonic pattern formation.


The nature of transcription selectivity of bacteriophage SPO1-modified RNA polymerase.

Escherichia coli and Bacillus subtilis RNA polymerase have almost identical transcription specificities on bacteriophage SPO1 DNA when assayed in a coupled transcription-translation cell free system. SPO1-modified B. subtilis RNA polymerase has altered transcription specificity. It is shown that rifampicin-inhibited E. coli RNA polymerase can completely block transcription of SPO1 DNA by rifampicin resistant B. subtilis enzyme, whereas it has no effect on transcription by SPO1-modified B. subtilis RNA polymerase. We conclude that the new transcription by SPO1-modified RNA polymerase results from newly recognized promoters, rather than by elongation of transcripts which could also be made by B. subtilis vegetative RNA polymerase.


Sigma factor is not released during transcription in Bacillus subtilis.

The relationship between sigma (sigma) and delta (delta) factors of Bacillus subtilis RNA polymerase has been analyzed during initiation of RNA synthesis. When core enzyme (E) containing delta factor (E delta) binds to DNA, the delta factor is released with the formation of an E-DNA complex. The addition of sigma to the E-DNA complex results in the formation of a stable E sigma-DNA complex which can synthesize RNA upon addition of nucleoside triphosphates. Sigma factor, significantly, is not released from the core during RNA synthesis. These results suggest that delta and sigma factors can act sequentially during initiation of RNA synthesis with delta acting as a DNA recognition factor and sigma acting as an initiation factor. The results do not preclude the possibility that E sigma can initiate RNA synthesis correctly since E sigma alone can bind to DNA and initiate RNA synthesis.


Different specific activities of the monomeric and oligomeric forms of plasmid DNA in transformation of B. subtilis and E. coli.

(1) The low residual transforming activity in preparations of monomeric, supercoiled, circular (CCC) forms of the plasmids pC194 and pHV14 could be attributed to the presence in such isolates of a small number of contaminating multimeric molecules. (2) E. coli derived preparations of pHV14, as in vitro recombinant plasmid capable of replication in both E. coli and B. subtilis, contain oligomeric forms of plasmid DNA in addition to the prevalent monomeric CCC form. The specific transforming activity of pHV14 DNA for E. coli is independent of the degree of oligomerization, whereas in transformation of B. subtilis the specific activity of the purified monomeric CCC molecules is at least four orders of magnitude less than that of the unfractionated preparation. (3) Oligomerization of linearized pHV14 DNA by T4 ligase results in a substantial increase of specific transforming activity when assayed with B. subtilis and causes a decrease when used to transform E. coli.


Cytogenetic localisation of the purine 1 and guanosine 1 loci of Drosophila melanogaster; the purine 1 locus specifies a vital function.

Three auxotrophic mutants at two loci (pur 1 and gua 1) apparently involved in purine metabolism were mapped cytologically to region 9E1-9E3 on the X-chromosome of Drosophila. Because mutants of pur 1 behaved as semi-lethals against deficiencies even on permissive medium, it appears that the pur 1 locus is vital to the fly and its auxotrophic mutants are hypomorphs.


Mapping the uroporphyrinogen III cosynthase locus in Bacillus subtilis.

The gene hemD taking part in the formation of uroporphyrinogen III from porphobilinogen was mapped by two- and three-factor transduction crosses in Bacillus subtilis. This gene codes uroporphyrinogen III cosynthase. The gene hemD is linked to the hemA locus and is located between the hemA and pheA loci.


Lysosomal enzymes and microbicidal capacity of activated macrophage.

A relation was sought between acid phosphatase contents and the presence of tubercle bacilli inside the peritoneal exudate cells (PEC) of normal guinea pigs and those immunized with BCG. This was done to investigate the role lysosomal enzymes play in the microbicidal capacity of the cell. In both normal and immune animals tubercle bacilli were present only in those PEC that contained acid phosphatase. Cells without acid phosphatase did not contain bacilli. Thus, only activated cells ingested bacilli. Under the conditions of these experiments, macrophage activation, as indicated by the presence of acid phosphatase, was not related to the immune status of the animal. Similarly, stimulation by ingestion of tubercle bacilli was not significant. Also, the number of acid phosphatase grains/cell did not influence the number of bacilli/cell. Thus, the acid phosphatase content of the cell did not correlate with the number of bacilli inside the cell. It was concluded that acid phosphatase may not be one of the factors that contribute to the microbicidal capacity of the cell.


Mycobacterium leprae and phenoloxidase activity.

Our earlier studies indicated that the enzyme o-diphenoloxidase was absent in Mycobacterium leprae separated from depromatous human tissues. At that time the bacilli were not available from any other source. The existence or absence of this enzyme in M. leprae recovered from infected armadillo tissues were reinvestigated. The intact cells which were metabolically active, failed to oxidize DOPA. Likewise, DOPA and its derivatives were not oxidized by the enzymatically active cell-free preparations from M. leprae. Upon incubation of DOPA for more than 2 h with whole cell suspensions or particulate fractions, there was no development of colour with an absorption maximum of 540 nm as has been reported for an intermediate of DOPA oxidation. However, DOPA and several phenolic compounds were very actively oxidized by mushroom tyrosinase. The results suggested that M. leprae is deficient in o-diphenoloxidase, and this enzyme is not an intrinsic characteristic of this mycobacterium.


[Ultrafine structure of Lpp-1 cyanophage-infected Plectonema boryanum cells].

The interaction of the cyanophage Lpp-1 with the trychomous blue-green alga Plectonema boryanum was studied. The stage of formation and maturation of phage particles was found to be preceded with the production of the DNA-phage pool similar in its morphology with that in trychomous bacteria of the order Caryophanales. Phagolysis of Pl. boryanum cells infected with the phage involved, apart from typical changes in the cytoplast, some distortion in the structure of young, unfinished partitions.


[Effect of lysozyme, ethylenediaminetetraacetate, magnesium and mannittol on spheroplast formation in Anacystis nidulans].

Three periods (the lag period and periods of intensive and decelerated spheroplast formation) can be detected in the action of lysozyme on the cells of Anacystis nidulans; this seems to be due to peculiarities in the cell wall structure of the cyanobacterium and heterogeneity of the culture. EDTA at concentrations of 0.175--0.7 mM has effect on the duration of the lag period but increases the rate of spheroplast formation during the subsequent periods. However, the action of EDTA in complex with lysozyme for 3 hours causes lysis of some of the spheroplasts being formed. The concentration of mannitol below 0.4 M decreases the yield of spheroplasts. The level of intact spheroplasts prepared from A. nidulans suggests that at least part of them is capable of reversing into whole cells.


Physical factors affecting absorbed dose to the skin from cobalt-60 gamma rays and 25-MV x rays.

When there is an absence of scattering material adjacent to the skin on the exit side of a megavoltage beam the dose to the skin is less than would be calculated using depth dose tables or isodose distributions measured in "semi-infinite" phantoms. Ionization measurements using a thin-window parallel-plate chamber show that the dose at 4 mg/cm2 from the exit surface is 14% to 16% less for cobalt-60 gamma rays and about 8% less for 25-MV x rays compared to the dose with full backscatter. As the angle of incidence increases the skin dose increases due to radiation scattered toward the surface. A method for the calculation of skin doses from tangential therapy beams is described.


Electrons as the cause of the observed dmax shift with field size in high energy photon beams.

For megavoltage x-ray beams, it is well known that the percent depth-dose increases considerably with field size in the buildup region, resulting in a significant shift in the apparent position of maximum dose, dmax. The nature of this increase has been investigated using a sweeping magnet placed just below the treatment head of a 25-MV linac. Measurements show that for increasing magnetic fields the dose in the buildup region is continually reduced, until a point is reached beyond which no additional reduction is observed. Here the buildup curve is essentially field size independent. These results clearly show that electrons are the primary cause of dose increase with field size in the buildup region, in contrast to a recent publication claiming that scattered photons are the cause. Further measurements were made by blocking out the primary beam at the level of the jaws and measuring the depth dose of the scattered electrons originating from the jaws. The results show that a thickness of approximately 1 gcm-2, of either polystyrene or lead, reduces the dose by a factor of two, providing further evidence that the scattered component of the beam consists of low energy electrons.


Improving the buildup and depth-dose characteristics of high energy photon beams by using electron filters.

The attributes of high energy photon beams, i.e., low surface dose, large dmax and improved %DD, are compromised with increase in field size. This is due to the relative increase with field size of the electron component in the beam, as shown by recent experiments done here using a sweeeping magnet. The present study shows that the advantages can be partially regained with the use of foils to remove electrons. Various thicknesses of Al, Cu, Sn, and Pb were placed in a 25-MV linac x-ray beam at several sites in the treatment head. Buildup curves were measured with a "pancake" chamber for various SSD and field sizes. The magnitude of improvement achieved is dependent upon field size, SSD, the atomic number of the foil material, and foil thickness. Pb foil (0.55 gcm-2) provided the best overall improvement. Surface dose reduction of 10%-20% can be achieved along with significant increase in dmax and %DD. These findings suggest a new design feature for the next generation of high energy linacs.


[Radiation risks and gonadal exposure in radiodiagnosis (author's transl)].

Radiation risk is estimated from the values on radiation risk of the International Council on Radiation Protection and from our own measurements. According to these, 1 malignant growth induced by radiation is found in about 160,000 urograms, 300,000 contrast enemata or 500,000 contrast meals. In radiodiagnosis of the central nervous system the values for carotid angiograms is about 60,000, for vertebral angiograms about 16,000, for computer tomography about 50,000 and about 500,000 examinations of the skull in two planes. A mutation-induced deformity due to radiation occurs in about 4,300--26,000 colon contrast enemata, about 43,000 to 280,000 contrast meals and about 41,000 respectively 14,000 urograms in men and women in the reproductive years.


In vivo sister-chromatid exchange: a sensitive measure of DNA damage.

A variety of chemical agents and X-irradiation were examined for their abilities to induce sister-chromatid exchanges (SCE) in vivo. In addition to demonstrating that several known mutagens and carcinogens are capable of inducing SCE in vivo, our studies indicate that the suspected carcinogen, tris-bromophosphate, can significantly elevate SCE levels. Comparison of the effects of these agents on SCE levels, chromosomal-aberration frequencies and cell-replication kinetics reveals that no consistent relationship exists between SCE levels and other indicators of cellular DNA damage. It is proposed that analysis of SCE induction in vivo may provide a useful technique for the screening of mutagenic and carcinogenic compounds.


Dose-response relations for dicentric yields in GO lymphocytes of man and crab-eating monkey following acute and chronic gamma-irradiations.

A comparison has been made of dicentric yields in GO lymphocytes between man and crab-eating monkey, Macaca fascicularis, after acute and chronic gamma-irradiations. With acute irradiation (49.6 rad/min) there was no significant difference between them, but for the chronic irradiation (17.1 rad/h) a significant difference was observed between the species. When the dose-response relations were fitted to the linear-quadratic model (Y = alpha D + beta D2), the species-difference observed for chronic irradiation was almost entirely due to change in the value of beta. In addition, after chronic irradiation the beta-value for monkey was almost negligible, but that for man was significant. Post-irradiation incubation experiment showed that cells with dicentrics were partly eliminated during the course of chronic irradiation, because there were appreciable reductions of dicentric yields (ca. 25% for both man and monkey at 400 rad) together with mitotic indices (ca. 30% and 60% for man and monkey, respectively, at 400 rad). Accordingly, it would be reasonable to postulate that GO repair for dicentrics other than selection mechanism must play a major role in the effects of low dose rate. It can be further suggested that GO-repair capacity for chromosal damages leading to dicentrics may be different among different primate species.


The effects of recombination-defective meiotic mutants in Drosophila melanogaster on gonial recombination in males.

Recombination-defective female meiotic mutants representing 7 loci in Drosophila melanogaster have been examined for effects on gonial recombination in males. These loci were chosen for study because they represent a broad range of the known types of defects in processes necessary for meiotic recombination and somatic chromosome stability. Alleles at 6 of the loci studied did not increase the frequency of gonial recombination in males, whereas a mutant at one locus was associated with an increase (about 10-fold) in gonial recombination. These results suggest that the defects in chromosomal metabolism caused by these recombination, and in some cases repair, defective mutants are distinct from those of the male-recombination promoting elements (Mr) recently isolated from many natural populations. Analysis of the spontaneous events detected in this study showed that a third to a half of the events detected are actually of mutational rather than recombinational origin.


Is there a proportionality between the spontaneous and the X-ray-induction rates of mutations? Experiments with mutations at 13 X-chromosome loci in Drosophila melanogaster.

The X-ray induction of recessive visible specific locus mutations at 14 X-chromsome loci was studied in Drosophila melanogaster using the "Maxy" technique. The X-ray exposure was 3000 R to 5-day-old males and the sampling of germ cells was restricted to mature spermatozoa. Presumptive mutant females recovered in the F1 generation were tested for transmission, allelism, fertility and viability in males. A total of 128 mutations (115 completes and 13 mosaics including those that were male viable as well as male-lethal) recovered among 38 898 female progeny were found to be transmitted. On the basis of the above frequency, the average mutation rate can be estimated as 7.8 X 10(-8)/locus/R; for mutations that were viable and fertile in males, the rate is 3.0 X 10(-5)/locus/R (49 mutations among 38 898 progeny). The frequency of mutations at the different loci encompassed a wide range: while no mutations were recovered at the raspberry and carnation loci, at others, the numbers ranged from 1 at echinus to 31 at garnet; in addition, the proportion of mutations that was male-viable was also different, depending on the locus. Schalet's extensive data on spontaneous mutations at 13 (of the 14 loci employed in the present study) loci permit an estimate of the spontaneous rate which is 6.1 X 10(-6)/locus (a total of39 mutations among 490 000 progeny); for mutations that were viable and fertile in males, the rate is 3.0 X 10(-6)/locus (19 mutations among 490 000 progeny). The mutability of the different loci varied over a 9-fold range. When the different loci are ranked depending on their relative mutability (for spontaneous and induced mutations) it is found that in general, loci that mutate spontaneously relatively more frequently are also those at which more mutations have been recovered in the radiation experiments and likewise, those that are less mutable spontaneously are also those that mutate less after irradiation. Since the data are limited, it is concluded that the above finding is not inconsistent with the assumption of proportionality between spontaneous and induction rates of mutations. On the basis of the above results, a doubling dose of 100 R can be calculated for the X-ray induction of specific-locus mutations in Drosophila spermatozoa.


Human infection from an unidentified erythrocyte-associated bacterium.

A 49-year-old splenectomized man had an infection from an unidentified, gram-positive, rod-shaped bacterium that adhered to the majority of his peripheral-blood erythrocytes. On transmission electron microscopy, the bacterium was seen to be extra-erythrocytic and was 0.2 micrometer wide by 1.0 to 1.7 micrometer long. It possessed a thick, granular cell wall, a trilamellar membrane external to the cell wall and prominent mesosomes. Attempts to cultivate the organism in vitro or to duplicate the patient's disease in splenectomized animals were unsuccessful. The patient's response suggested that the bacterium was susceptible to cell-wall-active antibiotics and to chloramphenicol but not to tetracycline. This bacterium may be the cause of other chronic, fever-producing, multisystem diseases of unknown origin.


Multiple toxin production by an isolate of Aspergillus flavus.

Three toxins were recovered from rice and wheat cultures of an isolate of Aspergillus flavus. The toxins were present simultaneously in the cultures after one or two weeks incubation and were identified as aflatoxin, cyclopiazonic acid and aflatrem, a recently identified indole-mevalonate metabolite.


[Effect of a dietary regimen with separated administration of protein on liver in the rat].

Rats received a protein-deficient standard diet and, separately at different hours of the day, protein (casein). The control group was given the standard diet added with casein. The livers of the rats were examined for histological and ultrastructural changes. The smallest changes were observed in animals which had received protein at eight o'clock. The control animals and the animals which had received protein at thirteen and nineteen o'clock, respectively, showed slight fatty infiltration of the liver.


Transplacental effects of ethylnitrosourea in a nonhuman primate, Erythrocebus patas.

A breeding colony of the Old World monkey Erythrocebus patas, an African species, has been established to study transplacental carcinogensis in a representative primate species. ENU was administered by repeated iv injections to pregnant females and to juveniles of both sexes. Repeated doses of 0.1 mmole/kg body weight per injection, given at 14-day intervals, are tolerated without apparent signs of toxicity by fetal and by pregnant and nonpregnant adult or juvenile monkeys. The internal can be reduced to 7 days, at least during the latter two-thirds of pregnancy. Large single doses (1.0 mmole/kg) are tolerated by pregnant females but are frequently abortifacient. These doses produce acute cytolytic damage to the cells of the periventricular germinal matrix in the fetal brain. Studies with [14C]ethyl-ENU indicate that there is no placental barrier to this carcinogen. As of December 1975, no tumors had been observed.


A structure-activity study on the influence of phenolic compounds and bioflavonoids on rat renal prostaglandin synthetase.

The stimulating or inhibiting influences of 33 phenolic compounds on the prostaglandin synthetase of rat renal medulla were tested. Dihydroxyphenylcarbonic acids clearly proved to be activators of the prostaglandin synthetase. Dimethoxyphenylcarbonic acids were ineffective. Aminoethylphenols as well as p-substituted monohydroxybenzenes with a carbonic acid side chain were clear stimulators in contrast to their alkyl derivatives which are pronounced inhibitors. Among the tested bioflavonoids (+)-cyanidanol-3 and morin were inhibitors of the prostaglandin synthesis. Flavonoids with polar substitution in 3,5,7-position such as rutin on the other hand showed activating properties.


Neurofibromatosis and optic glioma: clinical and morphological correlations.

Although an association between optic glioma and neurofibromatosis is well recognized, there has been no previous analysis of cases relating the locus of tumor to the presence or absence of von Recklinghausen's disease. This paper presents the results of such an analysis as well as a description of the comparative histology of optic gliomas in patients with and without neurofibromatosis. We conclude that optic gliomas in patients with neurofibromatosis present preferentially as multicentric lesions or as lesions affecting the optic nerve alone without invasion of the chiasm, that these tumors frequently differ morphologically, and that patients with neurofibromatosis and optic glioma may have a clinical course different from that of patients with optic glioma unassociated with neurofibromatosis. Previously published reports are reviewed in light of these observations.


Brain stimulation and reward: "pleasure centers" after twenty-five years.

"Self-stimulation" is a phenomenon whereby an animal (including a human being) will repeatedly stimulate its brain electrically, sometimes to the point of exhaustion. This phenomenon is robust and readily reproducible in many areas of the brain, particularly in nuclei and fiber tracts known to be monoaminergic, and it has been the basis for the study of reinforcement and learning mechanisms in the brain. The last 25 years of work on intracranial self-stimulation is reviewed with an emphasis on mechanisms, primarily catecholaminergic. Implications for learning and pain mechanisms are discussed.


Low cerebrospinal fluid gamma-aminobutyric acid content in seizure patients.

Gamma-Aminobutyric acid (GABA) has been implicated in the neurochemistry of epilepsy. Lumbar cerebrospinal fluid (CSF) GABA concentrations determined using an ion-exchange fluorometric assay reflect brain GABA content. The mean lumbar CSF GABA concentration among 21 medicated patients with intractable seizures was significantly lower (p less than 0.001) than that of 20 unmedicated normal volunteers. Patients with generalized tonic-clonic (grand mal) and complex partial (psychomotor) seizures had significantly lower (p less than 0.05) CSF GABA concentrations than those with simple partial (focal sensory/motor) seizures. Although lumbar CSF GABA levels in our seizure patients did not significantly correlate with serum concentrations of phenytoin, phenobarbital, or primidone, additional study of medication-free epileptic patients may be required to evaluate the possibility of anticonvulsant-drug-induced CSF GABA alterations.


[Value and significance of the immunologic determination of various serum sialoglycoproteins in rheumatic diseases of inflammatory nature].

A statistical method was used in the evaluation of alpha-1-antitrypsin, acid alpha-1-glycoprotein, and haptoglobin in patients with rheumatic fever, rheumatoid arthritis, gout, periarthritis, arthrosis with inflammation, and primary arthrosis. A highly significant increase was noted in rheumatic fever and rheumatoid arthritis, less so in arthrosis with inflammation and acute gout, while increases were poorly significant for periarthritis and not significant for primary arthrosis. It can be concluded that the determination of these serum sialoglycoproteins serves to distinguish inflammatory and degenerative rheumatism. Haptoglobin proved the most sensitive of the three. Moreover, there was a distinct correlation between ESR and the three indices. It is felt that sialoglycoproteins act as an indirect pointer to acute inflammation, since their degree of increase is related to the formation of inflammatory proteases.


The effect of some N solutions for parenteral nutrition on gastric and pancreatic secretion.

In patients without pancreatic disease Aminofusin L forte infused for 1 h did not stimulate gastric or pancreatic secretion. On the other hand, infusion of casein by hydrolysate led to a significant increase in the concentration and total output of HCl. 4 h intravenous infusion of Aminofusin L forte caused a transient but significant rise of the bicarbonate concentration, amylase activity and above all trypsin activity and output. The results show that N solutions used for parenteral protein nutrition influence in a different way both gastric and pancreatic secretion.


[Role of total parenteral nutrition in the treatment of ulcerous colitis].

Reference is made to the literature and personal experience in an assessment of the rôle of total parenteral nutrition in ulcerative colitis. An estimate is made of the position of this form of treatment with respect to conventional medical and surgical management, and its influence on the natural course of the disease. The results observed in 6 patients treated in this way are reported and the treatment protocol employed for the management of ulcerative colitis in a surgical department is described.


Total parenteral nutrition and inhibition of gluconeogenesis on tumor-host responses.

Rats bearing the Morris hepatoma No. 7777 were randomized into three treatment groups. Two of the groups received a nutritionally complete liquid formula diet per os ad libitum. One of these two groups received hydrazine sulfate (HS; an inhibitor of gluconeogenesis) twice daily (15 mg/kg) for 5 days. A third group of tumorous rats received the HS therapy and was given the liquid diet parenterally for 5 days. Tumorous rats fed per os, especially with HS therapy demonstrated inhibition of tumor growth, reduction of body and carcass weight, anorexia and decreased nitrogen retention. The combination of parenteral feeding and HS therapy sustained body and carcass weight with high nitrogen retention but stimulated tumor growth and was associated with liver toxicity. These results support the concept that cancer cachexia involves 'a systemic energy-losing cycle dependent on an interplay of tumor glycolysis and gluconeogenesis'.


Clinical trials on chemical radiosensitization of malignant melanoma of the choroid.

The experimental investigations carried out in model systems and on plant, animal or human tissues have demonstrated that it is possible to increase significantly the radiosensitivity of pigmented cells, including hamster melanoma. On the basis of these data, a clinical pilot study was undertaken in order to establish whether a similar methodical approach will prove effective if applied to the radiotherapy of malignant melanoma of the choroid in patients treated with 60Co gamma-rays according to Stallard's technique. Cuprenil and Chelaton Polfa were used as radiosensitizers. The results of therapy differed distinctly in the two groups of patients (receiving or not receiving radiosensitizing drugs), the rate of tumour regression being much higher in those with a parallel pharmacological treatment.


[Evaluation of the hypothalamo-hypophyseal-thyroid axis by means of TRH in patients with chronic open-angle glaucoma].

The diencephalo-hypophyseal axis was studied in a group of patients with chronic open-angle glaucoma by means of TRH. Nearly half of the patients studied presented with hypothalamo-hypophyseal dysfunctions. TRH increases the outflow coefficient in these patients but this increase seems to be due to a pharmacodynamic action inherent in the product, and appears prior to the release of thyroid hormone.


Hematoma after head and neck surgery--a major complication?

The role of hematoma formation in the development of complications after major head and neck surgery is surveyed retrospectively. An incidence of 4.2% was encountered. In all cases, the hematoma was identified within 12 hours postoperatively. Prompt surgical clot evacuation and reinstitution of drainage did not adversely effect the patient's subsequent course. Failure to adequately drain the hematoma resulted in increased wound dehiscence, major infection, and fistula. When properly treated, postoperative hematoma formation offers only the risks attendant with a second anesthesia; no subsequent related morbidity need be anticipated.


Office surgery in otolaryngology.

Rising hospital costs have prompted many surgeons to develop office surgical facilities. This can be particularly useful in the type of practice seen by the otolaryngologist. This paper deals with the requirements for an office surgical setup, the scope of surgery that can be carried out in the office, as well as the advantages and disadvantages of operating in the office. Of particular importance is the fact that one must be prepared for the emergency situation when operating in his office.


Concepts in the management of the lower nasal cartilages: anatomic contour--surgical sculpturing.

The lower nasal cartilages are sophisticated in contour as they exist in the normal position in the live patient. A different concept of the anatomic contour and twist of the cartilage is presented in anticipation of applying this information to surgical correction. Many cadaver dissections have been performed to demonstrate anatomic and surgical detail. The complex problem of surgical correction is simplified in four basic techniques from which the surgeon can select according to the existing anatomy. The contour of the "average normal" alar cartilage is presented from a different perspective, and average measurements for the remaining caudal segment are given as a guide for the surgeon.


Basic science approach to otoplasty for prominent ears.

Variations of the conchal setback operation for prominent ears have produced my best long-term otoplasty results. Additional use of the Mustarde mattress sutures combined with cartilage weakening techniques must be used when the anthelix cartilage is thick and flat or concaved, but they should never be used above the beginning of the inferior crus. Other additional techniques which can be used to supplement or replace the Mustarde sutures are radical postauricular skin excision and closure under tension, incision and suturing to sharpen the inferior crus, and mattress sutures from the periosteum to the fossa triangularsor anterior helix. Methods for correction of lobular protrusion are also discussed.


The effects of tying the neurovascular bundle during palatoplasty.

Controversy rages in the literature over the possibility of denervation and atrophy of the palate that may occur secondary to severance of the greater palatine neurovascular bundles during palatoplasty. A pilot study was undertaken to assess palatal bulk, mobility, sensation, and mucous gland population, as well as speech, in a group of cleft palate patients, some of whom had severance of the bundles during their palatal repair and some who did not. These same parameters were tested in a group of patients who had juvenile nasopharyngeal angiofibromata, in whom one bundle was tied and the other was not during the transpalatal exposure of the tumor. Severing the neurovascular bundle produced no appreciable differences between the two cleft groups except they all had depressed mucous gland counts. The procedure produced no problems in the angiofibroma patients.


Evaluation of sclera as a homograft in facial plastic and reconstructive surgery.

Augmentation of deficient soft tissue contours accounts for a large part of facial plastic and reconstructive surgery. An attempt to use homograft sclera in the feline animal model is presented. Augmentation of nasal dorsum and the chin contours was carried out in the cat model with preserved homograft sclera. Serial soft tissue radiographs and histologic study of the homografts demonstrated complete resorption of the grafts by six months. Further physical and chemical alterations of homograft sclera appear to be necessary prior to its implantation for the purpose of soft tissue augmentation.


Consideration of acoustic reflex magnitude (ARM) in cases of idiopathic facial paralysis.

Contralaterally elicited acoustic reflex growth functions were obtained from both ears of patients with unilateral idiopathic facial paralysis. Comparison was then made between the normal and impaired reflex arc by means of a simple calculation procedure. The resultant acoustic reflex magnitude (ARM) score was used to evaluate the symmetry of these responses, thereby providing an objective quantification of the functional status of the impaired reflex arc. These measures were found to be highly correlated with both the degree and rate of recovery of the facial motor impairment.


The kallikrein-kinin system in otitis media with effusion.

The kallikrein-kinin system was studied in middle ear effusions from 28 ears suffering from otitis media with either a purulent, mucopurulent, serous or seromucinous, or mucoid effusion. Kinin, kininogen, kininase, kallikrein, prekallikrein, and protein were measured in these secretions. The findings suggest that the concentration of kinin is greatest in the serous and seromucinous effusions and lowest in the mucoid effusion. This is also true for kininogen and total protein. These studies suggest that the vasoactive polypeptide system is present in most middle ear effusions and that the concentration of the components of this system are different for different effusions.


Experimental otitis media with effusion: an immune-complex-mediated response.

The possibility that immune complexes cause otitis media with effusion (OME) has been previously proposed. In order to test this hypothesis we developed an animal model in which immune complexes were injected into the middle ears of chinchillas and the animals killed at various time intervals thereafter. Moderate inflammatory changes were seen in animals killed four hours postinjection, whereas intense inflammation was observed in those killed at 24 hours. Inflammatory changes observed included capillary dilatation with increased capillary permeability, migration of polymorphonuclear leukocytes into the sub-mucosa, hemorrhage, and damage to and actual disruption of the subepithelial basement membrane. These changes are consistent with a complement-mediated acute inflammatory reaction. Although no definite conclusion can be made concerning the etiologic role of immune complex in OME, our findings show that immune complexes can cause acute inflammatory changes in the middle ear of the experimental animal.


Rheologic and transport properties of middle ear effusions from cleft palate patients.

Middle ear effusions represent respiratory secretions which are physiologically important to functional mucocilliary transport systems. Knowledge of middle ear mucus and methods of facilitating clearance continue to be important to cleft palate patients. Middle ear mucus was collected from the ears of children with cleft palate before surgical correction. Samples were dialyzed and lyophilized to yield mucus powder. This mucus was reconstituted at various nondialyzable solids (NDS) concentrations in TRIS-CI buffer. A physiochemical study of the middle ear mucus was then undertaken, since a mucociliary transport defect leading to serous otitis media (SOM) is an etiologic possibility.


Orbital complications of acute sinusitis: evaluation, management, and outcome.

Acute orbital cellulitis is most commonly caused by sinusitis. This complication is based on the anatomy of the sinuses, orbit, and their venous connections. A series of 134 patients is reviewed to demonstrate the etiology and clinical course of orbital cellulitis. Antibiotic therapy alone does not prevent permanent complications. Surgical intervention is found necessary in all age groups and is required in 20% of the study population.


The anatomy of the subglottic larynx.

There is little concensus concerning the boundaries of the subglottic space. To better define the subglottis, 50 head and neck surgeons were asked to define its anatomic limits. In addition, the larynx of each of 50 adult cadavers was removed and four measurements in the anterior subglottis were taken. The results revealed significantly smaller subglottic dimensions for women than for men. In most women, the cricothyroid membrane was situated less than 1 cm from the glottis in the anterior midline.


Composite nasal septal graft reconstruction of the partial laryngectomized canine.

Composite nasal septal grafts provide excellent autogenous replacement tissue for the partial laryngectomy defect. The added factor of a mucosa similar to that removed appears advantageous for preservation of the airway. Arytenoid preservation or replacement tends to improve glottic rehabilitation by pseudocord formation. It is believed that the composite nasal septal graft would be of special advantage in the patient who had received previous irradiation.


Development of the cochlea and its coiling mechanism.

The growth and shape of the membraneous labyrinth appears to be organized and restricted by the formation of the cartilaginous capsule. Coiling of the cochlear duct appears to be the result of the physical barrier and support provided by the cartilage cells differentiating from mesenchyme surrounding the otocyst. In addition, tissue interactions between this mesenchyme and the developing cochlear duct may be the source of a genetic message for the coiling mechanism.


Development of the sensory receptor cells in the utricular macula.

Normal CBA mice were timed for the developmental stage by the vaginal plug technique. The day of copulatory plug observance was designated as gestation day one. The developmental characteristics of the utricular macula sensory epithelium is described on an ultrastructural level from the 15th to the 19th day of gestation (approximate day of birth). The following pertinent observations are reported: (1) the formation of stereocilia begins prior to the 15th day and continues to approximately the 18th day, (2) the formation of the stereocilia suggests a mechanism of gradual transformation of existing cell surface microvilli, (3) the onset of the genesis of stereocilia precedes neuronal contact and cuticular plate formation, (4) stereocilia rootlets are forming before cuticular plate formation, (5) utricular sensory hair cells have undergone significant ultrastructural differentiation prior to the development of synaptic contacts, and (6) nerve chalice formation of type 1 sensory cells begins on the 18th day and is still incomplete at birth.


Evaluation of tympanic neurectomy and chorda tympanectomy surgery.

Thirty patients were treated by tympanic neurectomy, chorda tympanectomy, or both for a variety of conditions. Out of six patients with gustatory sweating treated by tympanic neurectomy, two patients were relieved of symptoms, two were improved, and two remained unchanged. In five cases of benign recurrent painful parotid swelling, only two patients noted improvement in symptoms. Seventeen patients suffered from drooling. Out of 12 postresection head and neck patients, 5 (41%) were improved following such surgery. Two of four cerebral palsy children initially had a good result. However, the long term follow-up of the patients demonstrated that the drooling recurred. An additional patient who suffered from drooling caused by bulbar weakness following a cerebrovascular accident had fewer problems with salivary secretions postoperatively. The pertinent anatomy and pathophysiology is outlined. The possible reasons for the relatively disappointing results achieved are discussed.


Arteriolar sclerosis as a cause of presbycusis.

Temporal bones, brains, and kidneys of 40 patients over 50 years of age were studied histopathologically, paying special attention to angiosclerotic changes. The histopathologic findings were correlated with audiometric and manometric records obtained while the patients were alive. A close relation existed among the lumen narrowing of the internal auditory artery, spiral ganglion atrophy, and hearing loss. The angiosclerotic changes of the Willis' circle, encephalomalacia, and hearing loss were also related.


Cochlear nerve projections following organ of corti destruction.

Experimental organ of Corti destruction results in (1) secondary loss of all type I spiral ganglion neurons, (2) development of type III spiral ganglion neurons, (3) degeneration of most cochlear nerve myelinated fibers, and (4) terminal degeneration in the ventral and dorsal cochlear nuclei. The first signs of degenerative changes occur by eight days after organ of Corti destruction and degeneration debris remains until 28 weeks after destruction.


Undergraduate medical education in facial plastic and reconstructive surgery.

Instruction in basic surgical techniques with practical experience is often minimized in the modern, compressed medical curriculum. The otorlaryngologist can fulfill a major need in this area by presenting instruction in these techniques with emphasis on their application to the face. The authors have developed a course which has been refined through the experiences of over 100 medical students at the University of Colorado Medical Center and has been uniformly well received by students and administration. The outline of the didactic presentation and organization of the practicum is presented.


Hypoplasia of the vestibular aqueduct and endolymphatic sac in endolymphatic hydrops.

Four temporal bones from three previously reported cases showing endolymphatic hydrops and pathology of the vestibular aqueduct (VA) and endolymphatic sac (ES) were investigated further. Pathology of the VA and ES was studied by measuring the sizes of the VA and ES, paying particular attention to the proximal rugose portions. A medial-view graphic reconstruction was created to delineate the course and size of the VA, as well as its correlation with neighboring structures (posterior canal and cochlea). In addition, 20 control temporal bones were selected and measured for quantitative study of the sizes of the VA and ES. The four pathologic temporal bones were shown to have small, simple, tube-like VA and ES, without surrounding bony pathology. This appeared to be congenital hypoplasia characterized by hypoplastic funnel-shaped dilatation of the VA and hypoplastic rugose portion of the ES. Anterior dislocation of the distal portion of the VA and poorly developed periaqueductal air cells were also noted in the pathologic bones.


Stria vascularis pathology and recovery following noise exposure.

The time course of chinchilla stria pathology (edema) and recovery after one and two noise exposures is quantitatively and qualitatively described. Gross stria edema is present one, three, and seven days following one noise exposure; stria edema is not as severe nor as frequent following two noise exposures. Stria cell and vessel pathology are also observed at seven and ten days after one, but not two, noise exposures. Possible mechanisms of stria pathology and recovery after noise exposure are discussed.


Paget's disease and hearing loss.

Hearing loss, tinnitus, and vertigo have long been associated with Paget's disease of the bone. We reviewed the records of 463 patients with Paget's disease who were seen in the otolaryngology department. Hearing loss was common. It was our observation that mixed hearing losses were part of the disease process. Sensorineural hearing loss was the most frequent loss, but it usually was not part of the disease process. Tinnitus, vertigo, or both were seen in about 20% of these patients.


Corticosteroid injections of the nasal turbinates: past experience and precautions.

Clinical experience with triamcinolone acetonide (Kenalog) injections into the nasal turbinates for allergic and vasomotor rhinitis is reported by two authors. Gratifying results have occurred in most of the over 60,000 patients treated, with no serious side effects. Two cases of intravascular injections of another corticosteroid reaching the retinal circulation are reported, and methods for preventing this complication are proposed.


Chronic bacterial tonsillitis: fact or fiction.

Chronic bacterial tonsillitis can be validly supported etiologically by quantitative bacteriologic methods. The following observations are based on a recognition that the mere presence of bacteria is much less significant than the level of bacteria present. The chronically infected adult patient may be characterized by tonsils subclinically harboring greater than 10(5) bacteria/gm as opposed to the control patient with 10(3) bacteria/gm. Useful features in predicting high bacterial levels are (1) low number of crypts, (2) presence of nodal hypertrophy, and (3) tonsils small by actual size. Estimated tonsil size, determined preoperatively, shows no statistically significant correlation with either actual size or degree of tonsil sepsis.


Permanent threshold shift and cochlear hair cell loss in the kanamycin-treated guinea pig.

The differential contribution of the inner hair cells (IHC) and the outer hair cells (OHC) in the mammalian cochlea to hearing sensitivity was assessed in six behaviorally-trained guinea pigs by comparing audiograms preadministration and postadministration of kanamycin, an antibiotic that predominantly destroys guinea pig OHC while leaving the IHC structurally unchanged. The results support the hypothesis that only the IHC of the cochlea responds to tones approximately 50 to 60 dB above the threshold of the intact cochlea.


Interruption of combined therapy: a factor in decreased survival.

Occasionally, during the course of combined (radiation plus surgery) treatment of head and neck malignancies, the patient experiences a profound response to radiotherapy alone and elects to decline the second phase of treatment, namely, surgery. After a variable interval, radiotherapy is reinstituted to a "curative" level. A series of 14 laryngeal and oropharyngeal carcinomas, treated in this disjointed fashion, has been examined with respect to long-term survival. The prognosis is extremely unfavorable, thus supporting a basic philosophy of continuing with the prescribed surgical treatment despite a dramatic response to noncancericidal doses of radiotherapy. The site and stage of tumor, radiation dosage, interval to completion of therapy, and incidence of local and distant metastases are examined. It appears that every effort should be made to provide continuity in the combined therapeutic protocol if the advantages of this mode of therapy are to be effective.


Bioelectric phenomena in the ototoxicity of nitrogen mustard.

The effects of nitrogen mustard on the electrical potentials of the inner ear were studied, and the results were correlated with the histopathologic findings which have been reported in nitrogen mustard ototoxicity. The endocochlear DC potential (EP) decreased rapidly after an injection of nitrogen mustard (NM). The amplitude of the cochlear microphonics potential (CM) diminished rapidly, and no substantial recoveries were observed. No significant changes in the magnitude of the negative potential of organ of Corti (NPOC) were observed. A large negative summating potential (SP) was recorded even when the amplitude of the CM had diminished.


Hypersomnia with periodic breathing (an acromegalic Pickwickian).

The syndromes of Pickwickian, Ondine's curse, and primary alveolar hypoventilation are respiratory disorders manifesting increased sleepiness and irregular respiratory rhythms. These disorders are currently grouped as hypersomnia with periodic breathing (HPB). Polygraphic techniques have lead to a reasonable hypothesis as to the pathophysiology of the multiple variants of HPB. Discernible causes of HPB have been attributed to both central and peripheral factors. Peripheral factors encompass those conditions relating to upper airway obstruction. An acromegalic person suffering the HPB syndrome secondary to laryngeal stenosis is described.


Blunt laryngotracheal trauma.

Management of blunt trauma to the larynx and trachea is based upon accurate assessment of the anatomic site of the injury, the tissue involved, the time since the injury, and the general status of the patient. Early and orderly diagnosis and classification result in early management, which is essential to maximize function and minimize morbidity. To evaluate the management and treatment results of patients with blunt trauma to the larynx and trachea, a retrospective study was performed. The office charts and hospital records of all patients with blunt trauma to the larynx and trachea from 1966 through 1976 were reviewed. Conditions studied included etiology of the trauma, initial signs and symptoms, pretreatment findings, management (primary and secondary), complications, and long-term results of management. Management results are discussed in comparison with reported results in the literature, and conclusions are presented regarding optimal treatment for the various classes of laryngotracheal injury.


Rhytidectomy (face-lift) in the otolaryngologic practice.

A surgical procedure is described that minimizes the lifting of the hairline in rhytidectomy by locating most of the incision inside the hair. Traction of the skin is directed at producing a soft, rounded contour. The author reports good results on 30 patients in two years' time. Appropriateness of rhytidectomy depends on psychologic factors and on biologic rather than chronologic age. Operation under general anesthesia is preferred and should be confined to a simple procedure. However, blepharoplasty, rhinoplasty, and mentoplasty are often performed at the same time. Forehead lifting is a desirable associated procedure in which the incisions can be joined. Cutting of the muscle fibers is preferred to resection of the frontal corrugator. Minilifting to obtain Oriental slant eyes is considered a wasted effort.


The Leyla retractor: use in acoustic neuroma and neurotologic surgery.

The Leyla retractor is a self-retaining retractor used in the translabyrinthine removal of acoustic neuroma and middle fossa surgery. It is used to maintain constant, even pressure on a decompressed sigmoid sinus and cerebellum in translabyrinthine surgery and the temporal lobe in middle fossa surgery. The Leyla retractor provides excellent exposure and greater freedom and dexterity for the neurotologist.


[Effect of parasitic protozoa on the physiological state of the body of the confused flour beetle (Coleoptera, Tenebrionidae)].

Studies were conducted of diseases of Tribolium destructor and T. confusum caused by parasites of the fat body, microsporidians of Nosema whitei and coccidians of Adelina tribolii. The infection of larvae of tenebrionid beetles with microsporidians and coccidians results in substantial changes in the metabolism of insects-hosts (respiratory metabolism is disturbed and activity of tissue catalase is reduced). Physiological characteristics of uninfected larvae of T. confusum and T. destructor differ considerably. In T. destructor the disease is more acute in its character and is accompanied by more sharp changes in metabolism as compared to T. confusum. On the basis of experiments conducted the author came to the conclusion that parasitic protozoans affect the physiological state of tenebrionid beetles in many ways. On the other hand the tenebrionids themselves are somehow affected by the host that apparently is stipulated by physiological and biochemical peculiarities of the organism of the latter.


[Modification of the usual method of detecting the state of blackfly (Simuliidae) larval infestation with microsporidians].

At a water temperature fo +1 to +4 degrees black flies larvae and microsporidians from them develop asynchronously that can be used for the diagnostics of microsporidiosis. The infection rate of black flies larvae increases after their being maintained at a temperature of +1 to +4 degrees during 8 days. This is 2.5-3 times higher as compared to the infection rate determined by the known method just after the sampling.


Maternal-fetal transfer of melatonin in the non-human primate.

Melatonin was detected in the circulation of the near-term rhesus monkey (Macaca mulatta) and baboon (Papio papio) fetus. We determined whether the source could be the mother by studying placental transfer of melatonin in the rhesus monkey. When [3H]melatonin was administered i.v. to the mother it promptly appeared in the fetal circulation; the rates of disappearance of [3H]melatonin in the maternal and fetal circulations were parallel. The rapid decrease in circulating [3H]melatonin was associated with a rapid accumulation of [3H]melatonin-metabolites in the maternal and fetal circulations. Although the pattern of appearance of metabolites was similar in both circulations, relatively less [3H]melatonin-metabolites appeared in the fetal circulation. Acute changes in total maternal plasma melatonin, experimentally produced by giving a 20 min infusion of melatonin, were rapidly reflected in the fetus. This suggests that a daily rhythm in maternal melatonin would generate a similar rhythm in the fetus. The fetal monkey pineal was found to have the two enzymes necessary for the conversion of serotonin to melatonin. It is, however, not known whether fetal melatonin synthesis is rhythmic or the extent to which it could contribute to circulating melatonin levels at this or earlier stages of gestation.


[2 new species of myxosporidians of the genus Myxoproteus from fish of the Celtic sea].

Two new species of Myxosporidia of the genus Myxoproteus from the Celtic Sea fishes are described. M. scoleciformis was found in the biliary bladder of the John dory, Zeus faber (on 1 from 4 fishes), M. formosus was found in the urinary bladder of the whiting Merlangius merlangus (on 2 from 9 fishes).


L-alanyl-L-tyrosine as a tyrosine source during total parenteral nutrition. Infusion at 0.5 and 2 mmoles/kg/day in adult rats.

Tyrosine peptides, such as L-alanyl-L-tyrosine, have excellent solubility and are potential sources of iv tyrosine. Infusion of L-alanyl-L-U-14C-tyrosine as part of a total parenteral nutrition regimen in the rat at a level of 0.5 mmole/kg/day resulted in rapid labeling of tissue tyrosine pools, production of 14CO2, incorporation of 14C-labeled tyrosine into protein, and minimal urinary losses (7.7%). Plasma tyrosine levels, however, remained at fasting. Infusion of L-alanyl-L-tyrosine at 2 mmole/kg/day increased plasma tyrosine above fasting levels and maintained tissue tyrosine at levels seen in orally fed control animals without increasing the percent lost in urine (5.5%). Rapid utilization of L-alanyl-L-tyrosine was noted at both infusion levels with no accumulation of peptide noted in plasma. Plasma and tissue free tyrosine pools were rapidly labeled, as was tissue protein. Radioactivity incorporated in tissue protein was shown to be tyrosine after acid hyrolysis.


Intrahepatic cholestasis associated with parenteral nutrition in premature infants.

Sixty-two premature infants less than 2,000 gm birth weight received parenteral nutrition (PN) during periods of respiratory distress with feeding intolerance. Intrahepatic cholestasis (direct bilirubin greater than or equal to 1.5 mg/dl) associated with PN developed in 14 or 23% of these infants. The mean time on PN to onset of cholestasis was 42 days, and the cholestasis persisted as long as the infants continued to receive PN. All five infants who had serial follow-up laboratory studies showed an eventual return of direct bilirubin levels to normal. The direct bilirubin level appeared to be the best clinically available test to monitor for the onset and to follow the resolution of this complication. The very low birth weight infants less than 1,000 gm appeared to be at an increased risk of developing cholestasis with an incidence of 50%. However, there was no correlation between the length of time PN was administered to onset of cholestasis and the gestational age or birth weight of the infants. These tiny premature infants also received PN for significantly longer periods of time, and the longer the infusions were administered the greater was the risk of cholestasis developing.


Effect of 2-4-dinitrophenol on intercellular communication in mammalian cardiac fibres.

The effect of 2-4-dinitrophenol (DNP) on cell communication, in canine Purkinje fibres, was investigated. It was found that DNP (0.5 MM) suppressed the electrical coupling in about 10 min. This effect of DNP was largely due to an increment in intracellular longitudinal resistance. The longitudinal movement of fluorescein (mol. wt. 320) along Purkinje strands, followed with the cut-end method, was also suppressed by DNP (0.5 mM). The decoupling action of DNP was related to release of Ca from intracellular stores and increase in free (Ca)i. The intracellular injection of EDTA reestablished the electrical coupling of Purkinje cells previously uncoupled by DNP. The results described in this paper indicate that cell communication in heart fibres is greatly dependent on the synthesis of high energy phosphate bonds.


Cloning of immunoglobulin kappa light chain genes from mouse liver and myeloma MOPC 173.

The organization of the kappa chain constant region gene was compared in DNA from an immunoglobulin-producing mouse myeloma (MOPC 173) and from liver. In situ hybridization using the Southern blotting technique revealed constant region gene-containing EcoRI-DNA fragments of 14 and 20 kb in the myeloma tissue whereas one EcoRI-DNA fragment with a length of 15 kb was found in liver DNA. After enrichment by RPC-5 chromatography and preparative electrophoresis the 14 kb fragment from MOPC 173 DNA and the 15 kb fragment from liver DNA were cloned in the bacteriophage lambda vector Charon 4A using in vitro packaging. Extensive characterization of the two fragments by restriction endonuclease mapping, in situ hybridization, and electron microscopy (R-loop and heteroduplex) showed that both fragments contain the constant region but no MOPC 173 variable region gene. Both fragments are homologous over a length of 12.5 kb including the constant region but differ from one another starting about 2.7 kb from the 5' end of the constant region gene. This indicates that the 14 kb EcoRI-DNA fragment from the myeloma tissue clearly resulted from somatic DNA rearrangement although it does not seem to carry the MOPC 173 variable region gene. These observations suggest that somatic DNA rearrangement of immunoglobulin light chain genes can involve both homologous chromosomes.Images


Sequence analysis of cloned cDNA encoding part of an immunoglobulin heavy chain.

The recombinant plasmid pH21-1 consists of mouse-derived complementary DNA (cDNA) in the E. coli plasmid pMB9. The mouse insertion has been completely sequenced, and encodes the CH3 domain and half the CH2 domain of the immunoglobulin gamma1 heavy chain. The predicted amino acid sequence differs at several positions from that previously published for this protein. The pattern of codon usage resembles that in some other eukaryotic messenger RNAs. A computer program has been used to predict the optimum secondary structure for the mRNA encoding the CH3 domain and the inter-domain junction.


Identification of a DNA polymerase beta-like form in Drosophila melanogaster adult flies.

DNA polymerase beta is widely distributed in the eukariotes. So far, few examples are known in which a DNA polymerase alpha -like form alone is reported. Surprisingly, DNA polymerase beta was not detected in Drosophila embryos, while it is present in the cells of multicellular species from sponge to mammals. In view of the relevance of Drosophila as a model biological system for studying the role of the various DNA metabolism enzymes in vivo we have reinvestigated the presence of the DNA polymerase beta-like form in Drosophila adult flies. Here we report the occurrence in Drosophila melanogaster adult flies of a DNA polymerase activity that, for its NEM(1) resistance, template specificity, sensitivity to ddTTP, sedimentation coefficient and nuclear localization can be classified as a beta-like form.


The prognosis for diabetes.

Microvascular disease is the predominant manifestation of the juvenile-onset diabetic after the third decade of survival, while large vessel atheroma is the major problem in the long-term survival of the maturity-onset diabetic. From the experience of a diabetic-eye clinic, we would estimate that only about 3% of patients attending a hospital diabetic clinic would have a severe form of diabetic retinopathy which might need specialized ophthalmic photocoagulation treatment. The long-term visual prognosis for patients treated in this way remains under review. Among metabolic factors associated with vascular disease, a deficiency of HDL cholesterol may be important in the future prognosis of maturity-onset diabetes.


HLA and insulin-dependent diabetes mellitus.

As suggested from clinical data and on the basis of human leukocyte antigen (HLA) data, insulin-dependent diabetes mellitus (IDDM) is a disease entity in itself and is different from non-insulin-dependent diabetes and other types of diabetes mellitus in aetiology and pathogenesis. HLA-B8 is associated with IDDM in all Caucasian populations studied, irrespective of the age of onset of the disease. HLA-B15 is associated with IDDM in populations of Northern European and British origin, while B18 seems to replace B15 in Southern European populations. IDDM is uncommon in populations where the HLA-B8 frequency is low, and in the Japanese IDDM occurs in association with Bw22. The HLA-Dw3 and Dw4 association with IDDM is stronger than that of the B alleles. Relative risks for B8 and B15 heterozygous and homozygous individuals are identical, i.e., no gene-dose effect exists. The relative risk of B8/B15 carriers is double that of relative risks of B8 and B15 alone, i.e., there are two IDDM-associated genes. The same applies to Dw3/Dw4 carriers. In families the phenotype IDDM segregates with a certain genotype, the diabetic proband's HLA haplotype. Only a small proportion of family members carrying the 'diabetic haplotype' develop IDDM.


Effects of d-amphetamine and methylphenidate upon auditory threshold in the squirrel monkey.

The effects of d-amphetamine sulfate and methylphenidate hydrochloride on auditory thresholds in ten squirrel monkeys were examined using a 4.2 kHz stimulus in a free field. The results indicated that d-amphetamine raised auditory thresholds but methylphenidate did not alter the thresholds. The elevation of sensory thresholds by d-amphetamine was in agreement with previous studies suggesting that the drug acts as a behavioral depressant in diurnal animals.


Prostaglandin synthetase inhibitors antagonize the depressant effects of ethanol.

Several studies indicate that ethanol may depress the central nervous system by altering neurotransmitter release. Evidence obtained from the peripheral nervous system suggests that prostaglandins act as negative feedback inhibitors of transmitter release. If a similar process occurs in the brain, then perhaps ethanol affects transmitter release via a mechanism involving prostaglandins. Prostaglandin synthetase inhibitors were administered to adult HS/Ibg male mice prior to intraperitoneal injection of a hypnotic dose of either ethanol, propanol, or t-butanol. A significant decrease in the length of alcohol sleep time was found: in the ethanol study, this was coupled with a significant increase in waking blood alcohol levels. These results indicate that inhibition of prostaglandin synthesis alters CNS sensitivity to the depressant effects of alcohol. When the same inhibitors were administered prior to other sedative hypnotics, i.e., pentobarbital and chloral hydrate, no effect was found. This suggests that prostaglandins may be specifically involved in the biochemical mechanism of alcohol depression.


Effect of brain peptides on hypokinesia produced by anterolateral hypothalamic 6-OHDA lesions in rats.

Intraventricular injections of substance P, TRH and somatostatin were administered to rats rendered hypokinetic by bilateral microinjections of 6-hydroxydopamine into the anterolateral hypothalamus, Only substance P in a dose of 0.30 micrigrams/rat significantly increased motor activity as determined by photocell counts in a 5 min test session immediately after administration of the peptide. Behavioral observations indicated that grooming and not locomotion was mainly responsible for the greater activity scores. None of the three peptides at the doses examined potentiated or reduced the increased activity induced by 1 mg/kg apomorphine. Stereotyped behavior was also not affected by previous injections of substance P and somatostatin but was enhanced in animals which had received 5 micrograms/rat TRH 30 min prior to apomorphine.


Drug metabolism by the fetal stump-tailed monkey (Macaca arctoides). Hepatic microsomal N-demethylation and glucuronidation as measured by radiometric assays.

Sensitive radiometric assays were adapted to study the development and kinetics of meperidine and methadone N-demethylation and morphine glucuronidation by microsomes isolated from livers of fetal stump-tailed macaques (Macaca arctoides). Times in development selected for study were midterm, three-quarter term, near term and newborn (0.5 h and 14 days). With appropriate attention to keeping blanks low, hepatic drug metabolism was demonstrable as early as midterm. Vmax for the N-demethylation reactions (nmole product/10 min/mg microsomal protein) increased throughout gestation, whereas the apparent Kms remained constant. With respect to morphine glucuronidation, all kinetic parameters remained constant throughout the last half of gestation.


[EEG follow-up studies following posttraumatic apallic syndrome in children].

Seventeen children, who had sustained craniocerebral traumata with posttraumatic apallic syndromes, were examined electroencephalographically for an average period of six years. Until incipient clinical remission of the apallic syndrome, the electroencephalographic results correlated essentially with the clinical picture; later on, there was observed only a relatively loose correlation between the electroencephalogram and the neurological or psychic condition. Despite serious and irreversible brain damage, complete normalization of the electroencephalogram could be observed in individual cases.


Long-stay patients in Danish psychiatric hospitals.

The numbers of long-stay patients in Danish psychiatric hospitals were studied, based on information from the Danish cumulative psychiatric register and from the census studies of patients in Danish psychiatric hospitals, performed at 5-year intervals since 1957. In 1977, 2079 (20%) of the in-patient population which had been admitted before 1957 were still in hospitals. This 'old long-stay' group has diminished exponentially, with an annual reduction of 7%. During the period 1972--6, the number of patients who, on any given day, had been in-patients or attending as day-patients for more than 1 but less than 2 years (the 'new long-stay') varied between 847 and 1089: an average of 20 per 100 000 total population. The ratio of in-patients to day-patients was approximately 4:1. Based on the decline of the 1972 cohort during the period 1972--7, and assuming a constant 'influx' of new long-stay patients and a constant exponential decline of the cohorts, the number of new long-stay patients, including day-patients, at equilibrium was estimated to be about 4300 or 85 per 100 000 total population. About 31% will be schizophrenics and about 43% will be patients with organic disorders. Ninety-four per cent of the number at equilibrium will be reached after 16 years for the diagnostic group with the slowest decline, schizophrenia. On 1 April 1976, 3106 long-stay patients were present, accumulated since 1 April 1972. Nineteen per cent of these patients were in day-hospitals. This type of institution was used especially for younger patients with schizophrenia and reactive disorders.


Accumulating long-stay in-patients in Salford: monitoring further progress.

Data derived from a psychiatric case-register are presented on the accumulation of new long-stay cases in Salford from 1967 to 1976. The analysis supports the general decline reported in an earlier shorter-term study except for the over 65s, where the trend was reversed. The implications of the findings are discussed.


Zimelidine: a therapeutic and pharmacokinetic study in depression.

Zimelidine, a bicyclic compound with a strong effect on the neuronal reuptake of 5-hydroxy-tryptamine and with weak anticholinergic actions, was evaluated for its antidepressant efficacy in a double-blind comparative trial with amitriptyline. In doses of 200 mg a day it was found to be as effective as 150 mg amitriptyline, but with significantly less subjective side-effects. The plasma concentration of zimelidine and its metabolite, norzimelidine, showed no significant correlation with therapeutic outcome.


Effects of locally applied dopamine to the nucleus accumbens on the motor activity of normal rats and following alpha-methyltyrosine or reserpine.

The motor activity of rats was investigated following bilateral application of various doses (0--80 micrograms) of dopamine to the nucleus accumbens. A high dose (80 micrograms) of dopamine increased the motor activity of normal as well as alpha-methyltyrosine- and reserpine-treated rats. It also increased the late motor activity (6--9 min) of normal rats, probably due to stimulation of postsynaptic dopamine receptors. Lower doses (10--40 micrograms) of dopamine suppressed initial (0--3 min) motor activity of normal rats, perhaps due to stimulation of dopamine autoreceptors on the dopamine nerve terminals in the nucleus accumbens with a subsequent inhibition of dopamine neurotransmission. An intermediate dose (40 micrograms) of dopamine was able to restore the motor activity of alpha-methyltyrosine-treated but not of reserpine-treated rats at all time intervals. This difference, indicating a restoration of the normal pattern of habituation by dopamine only in animals pretreated with alpha-methyltyrosine, suggests that normal behaviour is dependent on release of dopamine by nerve impulses.


Failure of naloxone to modify the effects of chlorpromazine and d-amphetamine on avoidance behavior in the squirrel monkey.

Lever-pressing by squirrel monkeys was maintained under a continuous avoidance schedule in which each response postponed for 30 s the delivery of an electric shock to the tail. Dose-response curves were determined for chlorpromazine (0.03--0.3 mg/kg) and d-amphetamine (0.03--1.0 mg/kg) administered alone and administered concomitantly with 1.0 or 10 mg/kg of naloxone. The dose-response curves for chlorpromazine and d-amphetamine were similar to those previously reported for monkeys under other schedules of shock-maintained behavior: Chlorpromazine decreased responding in a dose-related manner while d-amphetamine increased responding at low doses and disrupted behavior at the highest dose. Naloxone did not modify the effects of chlorpromazine and d-amphetamine. These results suggest that interactions observed previously between naloxone and nonopiate drugs on behavior in pigeons and rodents are not general phenomena in all animal species.