Seasonal incidence of cleft lips and cleft palates in Sweden, 1965--1974.

Seasonal trends of infants with cleft lips and palates born in Sweden during a ten-year period were investigated. The study is based on reports to the Swedish Register of Congenital Malformations supplemented with hospital data. Three different statistical methods were used: chi2 for heterogeneity between months, Edwards' method, and a squared sinus function technique. The tests were performed on birth date and date of last menstrual period (LMP) with and without correction for fluctuation in monthly birth rate. Statistical significant seasonality was found both for cleft lips with or without cleft palate (CLP) and for isolated cleft palate (CP) but only for LMP data. For CLP. a peak was found in March and for CP, in April.


Ulnar nerve compression at the elbow. Results of surgery in 85 cases.

An analysis after 1-18 years follow-up of 79 patients operated for ulnar nerve compression at the elbow. Favourable results seen after surgery seem independent of patients age and of duration and type of symptoms. Transposition to the front of the elbow with or without burial in an adjacent muscle was the operation of choice. When direct trauma has been given as an underlying cause the results are clearly worse. A surprisingly common association with Dupuytrens contracture and hypertension was encounted.


[Unrecognized posterior dislocations of the shoulder. Apropos of 6 cases].

Reporting six cases of posterior dislocation of the shoulder examined in a rheumatological setting, the authors emphasize the diagnostic difficulties in this condition. The post-epileptic aetiology is often unrecognized. Certain radiological techniques permit recognition of the dislocation, when the antero-posterior film shows little abnormal. The authors analyze the anatomical lesions, which sometimes include fracture, and review the orthopaedic and surgical treatments, and the results obtained.


[Chemotaxis of human granulocytes "in vitro". Study of inflammatory rheumatic diseases].

68 mesures of chemiotaxis of the blood granulocytes carried out in 42 patients suffering from systemic lupus erythematosus (SLE-17 cases), rheumatoid polyarthritis (RP-15 cases) and sclerodermia (SD-10 cases) showed a deficit in 15 cases. The deficit seen is cellular or plasmatic in the former two conditions (SLE & RP) but purely cellular in the sclerodermia. In SLE there is a relationship between the chemiotaxic deficit and a renal attack or a reduction in complement. In RP a relationship was established between chemiotaxis and a marked rise in VS (?) (synovial volume ?) and the rheumatoid factor titre. A relationship with a visceral attack was seen in SD. Contrary to other studies reporting a constant chemiotaxic deficit in these conditions, the present work shows that the deficit : 1. exists in only a minority of patients ; 2. is transitory ; 3. is not associated solely with granulocytes but may also be related to plasmatic factors. The diminution of chemiotaxis which is always seen in the acute phase of the illness may result from the reduction on the quantities of less reactive granulocytes in the peripheral blood ; the most reactive pass out through the walls of the vessels and move towards the foci of inflammation.


Burn injuries in Finland.

In the present investigation the burn injuries in Finland are estimated for a non-selected burns population. Annually 0.4% of the population seek medical care for burn injuries. The incidence of burns cases requiring hospital admission is 35/10(5) inhabitants/year. After initial treatment in the emergency ward, approximately 10% of burned adults and up to 25% of burned children are hospitalized. Of all burns cases requiring hospitalization, 55% are children under 15, 40% are adults of working age and only 5% are over 65 years of age. Men comprise two-thirds of the patients. The estimated bed capacity according to data collected is 20 per one million inhabitants (16 in the case of a continuous 100% load): 12 for adults and 8 for children. Of all the fatalities from burns, approximately 70% of deaths occur immediately from injury. The overall hospital mortality of burned adults is 5%, and 1% in children. The most typical burned child is a toddler with a burn covering less than 5% of the skin surface. The average burned adult in hospital is a man of 42 with 12% burn of total skin surface (3% of third degree) and who is discharged after 17 days of hospitalization.


Acute effects of burn injury on tissue gas tensions in the rabbit.

Early effects of 10% full-thickness skin burn on subcutaneous tissue PO2 and PCO2 levels were studied in anesthetized rabbits. Tissue gas tensions were determined by means of implanted Silastic tonometers in two different areas in each animal--the burn site itself, and an area remote from the injured tissue. Thermal injury resulted in a rapid, progressive decrease of the tissue PO2 in both locations, with the greatest decrease at the burn site. The minimum PO2 levels were achieved 3-6 hours post burn. The POC2 values increased markedly both in the burn areas and in the distant tissues immediately after the trauma and reached their maximum within 1-3 hours post burn. The greatest accumulation of carbon dioxide occured at the burn site. Six hours after burn the tissue PCO2 levels had been normalized. During the 6-hour observation period the mean arterial PO2 of the burned animals increased gradually from 73 to 95 mmHg, while the mean arterial PCO2 decreased by more than 50% of the original level. The latter effect was probably caused by hyperventilation. Intra-arterial injection of 5 ml of arterial blood from a burned rabbit into a control animal 3 hours post burn induced a significant decrease in cardiac output as well as decline in arterial, intraperitoneal, and tissue PO2 levels in the control rabbit, probably due to a circulatory depressant factor(s) present in the burn blood. When the same test was carried out one hour post burn or with normal blood, no decrease in oxygen tension occurred.


Tear drainage. Reconstruction by implantation of a glass tube prosthesis a.m. Lester T. Jones. Case report.

Good results are reported in patients with tear flow obstruction treated by implantation of a pyrex glass tube drain. Eight such drains were placed in seven patients with obstruction of the lacrimal canaliculi. Dependent drainage is established and this is aided by the negative pressure in the nose during inspiration.


The surface morphology of the melanoma cell. A scanning electron microscope study on the primary cutaneous melanoma.

The surface morphology of the melanoma cell in situ is summarized with regard to a study undertaken to elucidate the appearance of melanocytes and their differentiation in the surroundings of the malignant melanoma. Despite a non uniform cell pattern, several characteristic changes were found. The cells were 2-3 times the size of normal melanocytes, a number being differentiated by dendrites. The surface of the cell was marked by a numerous extensions, a number of which had differentiations that indicate a special function, though some smooth-surfaced cells were also found. It is possible that cell surfaces with many bulges and extensions are an expression of an unstable, undulating surface which could be of significance for the uncontrolled growth and metastasis of tumours.


Unilateral condylar hyperplasia and the associated deformity of facial asymmetry. Case report.

The etiology of unilateral condylar hyperplasia is obscure. We believe that it is due more likely to an intra-uterine influence rather than to genetic disturbances. The disorder appears to have its basis in the cartilagenous growth centre of the mandibular condyle. The clinical picture varies a great deal, depending upon the onset of the growth upset relative to the age of the patient and the rate of growth. Two cases are reported. In one patient the anomalous growth pattern was apparent particularly in the condylar neck, which showed marked elongation, thickening and angulation. In the other patient the entire condyloid process appeared proportionately enlarged. The typical clinical history is one in which the patient had been aware for many years of progressive deviation of the jaw. Pain in the T.M.J. regions is rarely the presenting symptom. With recent advances of oral surgery, restoration of malocclusion and facial disharmony can be achieved by approaches other than the traditional procedure of condylectomy.


Toxic effects of cadmium microparticles on the respiratory system. An experimental study on rats and mice.

An experimental study on rats and mice. Scand. j. work environ. & health 3 (1977) 116--121. Experiments on male, specific pathogen-free rats (193) and mice (66) are reported. The test and control animals received a single 15-min exposure to cadmium (cadmium oxide) and aluminum (alumina) microparticles, respectively. The air cadmium content was 10 mg/m3, and 4 microgram of this metal was retained by the lungs of the rats. The animals were observed for 24 days. The following significant differences appeared between the control and test groups: in the cadmium exposed rats the relative lung weight (percentage of body weight) became temporarily higher; the absolute number of alveolar macrophages decreased at first and then increased; numerous polymorphonuclear and lymphocytic cells appeared in the alveoli. According to these inflammatory phenomena, at the 48th h after exposure, there was an alteration in the clearance kinetics of inhaled bacteria and an increase in the death rate of cadmium exposed animals following a test infection with Salmonella enteritidis (rats) or Pasteurella multocida (mice) aerosols. The mechanism of cadmium toxic action on the respiratory system is discussed.


Tracheobronchial deposition of inhaled particles in rabbits.

Tracheobronchial deposition of inhaled particles in rabbit lung was studied after exposure to monodisperse aerosols 4--9 micrometer (aerodynamic diameter). Deposition was measured in terms of the particle content in free dissected bronchial sections from formaldehyde exposed and dried lungs. The free dissected part consisted of the lower section of the trachea and the lobe bronchi with their extensions from the five lobes. Deposition in this part of the tracheobronchial tree varied according to particle size, exposure technique, and individual. The range of the individual variation was about the same (300%) as the difference in deposition caused by changes in particle size (4 to 7 micrometer) and exposure technique (tracheal or oral tube). The individual variation could not be explained by any physiological factor, such as contraction in the respiratory tract. Rabbits treated intravenously with atropin had the same tracheobronchial deposition as a control group. On the other hand the individual variation in deposition could be explained by some anatomical factor since airway diameter and bronchial deposition showed a significant negative correlation.


Exposure of animals and man to toluene.

Twenty rats were exposed for 60 min to 14C-labeled toluene (1,950 mg/m3) in the inspired air. The largest amounts of toluene and its metabolites were found in the white adipose tissue. In a second series of experiments seven healthy male subjects were exposed to 375 mg/m3 of toluene in the air rest and during light, moderate and heavy physical exercise on a bicycle ergometer. The duration of each exposure period was 30 min. Of the seven male subjects three were thin, one was slightly overweight, and three were excessively overweight. The concentration of toluene in the alveolar air and the total uptake of toluene were determined during exposure. The thin subjects had a higher concentration of toluene in alveolar air than the other subjects both at rest and during exercise. The total uptake of toluene in the body during exposure showed that the subjects with the least amount of adipose tissue had the smallest uptake and the subjects with the largest amount of adipose tissue had the largest uptake.


Work stress in long-line bank fishing.

The circulatory strain on three Faroe Island and two Norwegian fishermen during long-line bank fishing was assessed by the computerized analysis of their heart rates continuously recorded by portable tape recorders. The urinary excretion of catecholamines was assayed as an indicator of stress response. The average work load of the three Faroe Island deckhands was rather moderate; it corresponded to 26--33% of the heart rate reserve (HRR). However, heart rates higher than 50% of the HRR (9--18 min/24 H) as well as peak heart rates up to 165 beats/min indicated periods of intense physical strain, especially when the fish were being unhooked, an operation which, as a rule, cannot be endured for more than about 25 min at a time and which necessitates a work schedule of job rotation. These observations were confirmed by the findings made on board the Norwegian vessel. The urinary catecholamine excretion rates were lower than those of coastal fishermen and of the same order of magnitude as the excretion rates observed in trawler fishermen. It is concluded that, contrary to general belief, bank fishing need not be unsuitable for older fishermen, provided an effective system of job rotation is practiced and the size of the crew is large enough to allow for an adequate amount of sleep even during periods of exceptionally good fishing.


Saltatory motility of uninserted trichocysts and mitochondria in Paramecium tetraurelia.

In the subcortical regions of the ciliate Paramecium tetraurelia, mitochondria and uninserted trichocysts each display saltatory motility with individual characteristics, making them distinguishable from each other and from cellular cyclosis. The saltatory motion of trichocysts is implicated as the means of transporting new trichocysts from the cytoplasm to their ultimate locations in the cellular cortex. Saltatory motion may also be a factor in the intracellular distribution of mitochondria.


Erythrocyte lipids in heterozygous carriers of duchenne muscular dystrophy.

Erythrocyte membranes from heterozygous carriers of Duchenne muscular dystrophy exhibit a diminished amount of palmitoleic acid when compared to membranes from normal subjects. A similar, but more variable, diminution is observed in the case of patients with this disorder. The change in fatty acid composition appears related to a low membrane triglyceride content and may provide both a possible technique for carrier detection and a clue regarding pathogenesis.


Glyoxalase I polymorphism in the mouse: a new genetic marker linked to H-2.

Two electrophoretically distinct variants of glyoxalase I (Glo-I) are present in mouse (Mus musculus). The two forms are controlled by two codominant alleles Glo-1a (common) and Glo-1b (rare) at an autosomal locus. A linkage study showed that Glo-1 maps at approximately 3 centimorgans from the Ss locus of the H-2 histocompatibility region. A similar linkage relationship exists in man between GLO and HLA, the human homolog of the H-2 gene complex. Thus, the chromosomal segment evolutionarily preserved in the two species is longer than previously suspected, and it includes genes with no obvious functional relation to the other components of the major histocompatibility complex. Several features of the Glo-1 polymorphism in the mouse recommend it as a marker of choice for the H-2 region.


Elastase release from human alveolar macrophages: comparison between smokers and nonsmokers.

Alveolar macrophages from smokers, in contrast to those of non-smokers, release elastase into serum-free culture medium. Since enzymes that digest elastin produce pulmonary emphysema in experimental animals, release of elastase by alveolar macrophages from smokers suggests that these cells are important in the pathogenesis of emphysema of smokers.


How many anticodons?

Much new information on codon composition is becoming available from the sequencing of molecules of DNA and RNA. The "wobble rules" for codon-anticodon pairing are applicable to this information. These rules provide for only 54 anticodons to pair with 61 codons, because the base A is not found in the first position of anticodons.


Testing the commitment theory of cellular aging.

The commitment theory may explain both the finite lifespan of diploid fibroblasts and the apparent immortality of transformed lines. Potentially immortal cells are assumed on division to generate with some fixed probability cells committed to senesce after a specific number of divisions. During the period between commitment and senescence, cells are assumed to maintain normal growth so that the uncommitted cells are diluted by committed ones and may ultimately be lost in subculturing. A number of predictions of this model are described and experiments strongly supporting the theory are reported. We conclude that the limited growth of diploid fibroblasts is, in effect, an artifact of normal culturing procedures.


Vibrio cholerae, Vibrio parahaemolyticus, and other vibrios: occurrence and distribution in Chesapeake Bay.

Vibrio cholerae was isolated at several locations in Chesapeake Bay in fall 1976 and spring 1977. Strains induced fluid accumulation in rabbit ileal loops and positive activity in Y-1 adrenal cells. Vibrio cholerae, Vibrio parahaemolyticus, and related vibrios show a spatial and temporal distribution characteristic of Vibrio species in an estuary. The Vibrio cholerae strains isolated from Chesapeake Bay represent serotypes other than O-group I--that is, so-called nonagglutinable vibrios--and are not recognized as a serious epidemic threat, although they have caused cholera-like diarrhea sporadically.


beta-Endorphin: endogenous opiate or neuroleptic?

The opiatelike neuropeptide beta-endorphin produces a spectrum of effects that contrasts with that induced by the neuroleptic haloperidol. Rats injected intraventricularly or directly into the periaqueductal gray with beta-endorphin (0.5 to 50 micrograms) exhibited rigid immobility accompanied by the loss of righting reflex; the period of rigidity was preceded or followed (depending upon dose) by a state of hyperactivity. In contrast, no dose of haloperidol tested (0.5 to 12 milligrams per kilogram) produced rigidity, loss of righting reflex, or behavioral excitation. Furthermore, whereas animals injected with haloperidol remained stationary on a vertical grid, rats injected with beta-endorphin typically slid off the grid. Moreover, combined beta-endorphin and haloperidol treatment produced flaccidity in most animals. These results do not support the contention that this opiatelike peptide may be a naturally occurring neuroleptic.


Interdependence of the nigrostriatal dopaminergic systems on the two sides of the brain in the cat.

The release of [3H]dopamine in vivo was estimated in the left and right caudate nuclei of the cat during the continuous superfusion of the two structures with L-[3,5-3H]tyrosine by means of two "push-pull" cannulas. A lesion made in the left substantia nigra interrupted the release of [3H]dopamine in the ipsilateral caudate nucleus and was associated with a simultaneous increase in the release of [3H]dopamine on the contralateral side. The release of [3H]dopamine also decreased in the left caudate nucleus and increased in the right structure when dopamine was applied to the left substantia nigra which reduces the activity of the left dopaminergic pathway. A total of 120 estimations of the spontaneous release of [3H]dopamine were made simultaneously in the left and right caudate nuclei during periods characterized by a stable physiological state of the animals, and 76% of the estimations showed that an increase in the release of [3H]dopamine on one side corresponded to a decrease in the release of [3H]dopamine on the other side, and vice versa. These results demonstrate a close relation between the two nigrostriatal dopaminergic systems.


Reversal of cardiopulmonary failure during active sleep in hypoxic kittens: implications for sudden infant death.

Experimentally induced hypoxia in kittens precipitated episodes of depressed respiration and irregular cardiac function during quiet sleep, waking, and transitional states. The onset of active sleep stimulated both breathing and heart rate and decreased abnormal variability in these functions. However, hypoxia markedly reduced the proportion of active sleep. These data suggest that active sleep protects against respiratory and cardiac abnormalities in infants. Chronic hypoxemia or other factors that reduce active sleep in infants, including the normal developmental decrement in this state, may increase the risk of cardiopulmonary failure and death.


Blind man living in normal society has circadian rhythms of 24.9 hours.

A psychologically normal blind man, living and working in normal society, suffered from a severe cyclic sleep-wake disorder. Investigations showed that he had circadian rhythms of body temperature, alertness, performance, cortisol secretion, and urinary electrolyte excretion which were desynchronized from the 24-hour societal schedule. These rhythms all had periods which were longer than 24 hours and indistinguishable from the period of the lunar day.


Increasing frequency of thyroid goiters in Coho salmon (Oncorhynchus kisutch) in the Great Lakes.

Coho salmon collected during the 1976 spawning runs from Lakes Michigan, Ontario, and Erie had overt goiter frequencies of 6.3, 47.6, and 79.5%, respectively. These represent significant increases over the frequencies observed in previous years. Epizootiological data suggest that environmental goitrogens (possibly pollutants) may be involved in the etiology of the thyroid disorder.


Carbon-14-labeled diethylstilbestrol synthesis by the McMurry method: concurrent formation of hexestrol.

Isotopically labeled diethylstilbestrol prepared from p-methoxypropiophenone by coupling with TiCl3-LiA1H4 contained approximately 50% hexestrol. Nonlabeled preparations and a subsequent labeled preparation had less than 2% hexestrol in them. Initial examinations for purity by gas-liquid chromatography, thin-layer chromatography, and isotope dilution did not show the presence of hexestrol. Specific ion monitoring of a gas chromatography-mass spectrometry determination revealed the presence of the deithylstilbestrol-hexestrol mixture.


Metal mutagens and carcinogens affect RNA synthesis rates in a distinct manner.

Five metal salts (lead, cadmium, cobalt, copper, and manganese),which are mutagenic or carcinogenic, decreasing the fidelity of DNA synthesis in vitro, stimulated chain initiation of RNA synthesis at concentrations that inhibited overall RNA synthesis. In contrast, other metal salts (zinc, magnesium, lithium, sodium,and potassium) not in this category inhibited chain initiation of RNA synthesis at concentrations that inhibited overall RNA synthesis.


Axon-sparing brain lesioning technique: the use of monosodium-L-glutamate and other amino acids.

Infusions of monosodium-L-glutamate into the rostral hypothalamus, believed to contain neurons mediating satiety, produced persistent hyperphagia and obesity, thus suggesting that a brain lesion had been produced. Similar infusions into the caudal hypothalamus, believed to contain unmyelinated axons of passage that mediate satiety, failed to alter food intake or body weight. Histological examination of the affected tissue confirmed the behavioral evidence that suggests that this technique spares axons but destroys cell bodies. Infusion of several other amino acids also damaged neurons while sparing axons of passage.


Regenerating afferents establish synapses with a target neuron that lacks its cell body.

When the axons of crayfish tail-fan mechanoreceptor neurons are severed, the axons regenerate into the central nervous system and after 2 to 6 weeks reestablish functional contacts with their standard interneuronal target cells. Removal of the cell body and hence the genes of the largest of these interneurons does not interfere with the successful reestablishment of synapses between it and its afferents.


Spatial frequency and the mediation of short-term visual storage.

The perceived duration of a photopically illuminated, fixated grating presented for 50 milliseconds increased (from 300 to 500 milliseconds) with spatial frequency (0.9 to 15 cycles per degree). This suggests a sustained neural channel contribution to short-term visual storage, and argues against a pure photoreceptor, especially a rod, locus for such storage.


Corneal endothelium damage with intraocular lenses: contact adhesion between surgical materials and tissue.

Intraocular lenses destroy corneal endothelial cells by contact adhesion between the acrylic lens and endothelial surfaces during cataract surgery. Glass and rubber surgical glove surfaces produce similar cell damage. This phenomenon may be important in many surgical procedures and appears to be preventable if a hydrophilic polymer interface is interposed between contacting tissue and the surfaces of materials used.


Carcinogenic risk assessment.

Carcinogenic risk assessment involves a mixture of statistical, scientific, and public policy considerations. Concepts in current use, such as "no observed effect levels" and "virtual safety," and the problems in implementing them by means of dose-response models, particularly the probit-log dose and linear models are reviewed. The upper limits to risk provided by some conservative procedures are inconsistent with coherent balancing of risks and benefits. A common basis to the dose-response curves describing both carcinogenic and noncarcinogenic effects is to be found in deactivating reactions. A simplified model in which a toxic substance is activated and deactivated in separate and simultaneous reactions is presented and the dose response curve implied by the model is deduced. This curve has the general form of a hockey stick, with the striking part flat or nearly flat until the dose administered saturates the deactivation system, after which the probability of a response rises rapidly. Such a curve describes the Bryan-Shimkin methylcholanthrene-tumor incidence dose response curve as well as the probit log-dose model. The concept of a saturation dose is relevant to risk assessments for carcinogenic and noncarcinogenic substances alike.


The code of the scientist and its relationship to ethics.

Scientist's norms (principally honesty, objectivity, tolerance, doubt of certitude, and unselfish engagement) are in danger of serious distortion unless broadened to apply to the relations between scientists and nonscientists. Also needing supplementation is an ethic of development appropriate to a fast-changing society and advanced as an approach to the more effective and humane regulation of cultural and technological development. Because of their genetic relationships the code of the scientist and the ethic of development are probably complementary and together may overcome the shortcomings of each taken separately. Taken together, furthermore, they indicate the possibility of a humane world order based on the cooperation of a community of scientists and its public.


Liposome accumulation in regions of experimental myocardial infarction.

The uptake of liposomes bearing positive, negative, or no net charge on their membrane and containing a radioactive tracer, [99mTc]diethylenetriamine pentaacetic acid, was studied in 12 intact dogs 24 hours after the induction of myocardial infarction, and compared to the relative regional myocardial blood flow determined from radioactive microspheres. Positively charged and neutral liposomes concentrate in infarcted regions against a flow gradient, while negative liposomes are passively distributed according to regional blood flow. Because positively charged and neutral lipisomes concentrate in infarct areas and have the ability to incorporate pharmacologic agents in their aqueous or lipid phase, they may serve as vehicles for drug delivery to infarct zones of low flow.


Screening for twin pregnancy.

A group of 590 women who, 4 to 5 weeks after their last menstrual period, were confirmed to be pregnant, as measured by the human chorionic gonadotropin (hCG) by radioreceptor assay. Nine of these women had serum hCG levels approximately twofold higher than the others and were suspected of having twin pregnancy. When these women were tested at 12 weeks of gestation, pelvic sonography confirmed twin pregnancies in all the nine cases. Serum hCG levels thus provide a simple, rapid, and easy method to detect twin pregnancy.


Radioimmunoassay for antibodies to cytoplasmic ribosomes in human serum.

A radioimmunoassay for the detection of antibodies in human serum to tritium-labeled HeLa cell cytoplasmic ribosomes was developed with the use of Macaloid for the inhibition of endogenous ribonuclease activity. Antibodies were observed in the serum of patients with systemic lupus erythematosus in high incidence and titer. Patients with rheumatoid arthritis and chronic active hepatitis manifested a lower incidence and titer of antibodies to ribosomes, whereas serums from normal individuals and from patients with sarcoidosis, chronic glomerulonephritis, and malignant tumors showed no significant reactivity with cytoplasmic ribosomes. Maximum inhibition of the reaction was achieved with unlabeled HeLa cell ribosomes or rat liver ribosomes and partial inhibition by purified ribosomal RNA.


13-cis-Retinoic acid: inhibition of bladder carcinogenesis induced in rats by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Transitional cell carcinoma was induced in the bladders of male Fischer rats by 12 oral doses of the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Feeding of 13-cis-retinoic acid after completion of carcinogen treatment diminished the number and severity of cancers and other proliferative lesions of the bladder.


Amacrine cells in Necturus retina: evidence for independent gamma-aminobutyric acid- and glycine-releasing neurons.

About one-half of on-off ganglion cells have inhibitory postsynaptic potentials (IPSP's) which are blocked by strychnine, while the remainder have IPSP's which are blocked by picrotoxin or bicuculline. These antagonists do not abolish light activity of the presynaptic inhibitory neuron, the amacrine cell. The existence of separate gamma-aminobutyric acid- and glycine-releasing amacrine cells is implied by these results.


Interactions between rod and cone systems in the goldfish retina.

Signals from both the rod and the cone receptor systems converge upon the same retinal ganglion cell, but only one or the other of these systems appears to be effective at any particular level of adaptation. In this report we provide evidence that the change from one receptor system to the other is not simply due to the two systems having nonoverlapping dynamic ranges; rather, there is a distance-dependent interaction between the two systems.


Trichromatic vision in the cat.

Many cat retinal ganglion cells (types X, Y, and W) have inputs from three separate cone systems. Those with peak sensitivities at 450 and 555 nanometers have been previously shown. A gamma max cone with a peak sensitivity of 500 nanometers can be differentiated from other cones by spectral sensitivity and from rods by receptive field differences, functioning above rod saturation levels, and by cone-rod breaks in the dark-adaptation curves. The similarity of the three-cone cat retina to the extramacular retina of the rhesus monkeys suggests that the cat may have photopic trichromatic vision.


Addiction, alcoholism, and anesthesia.

The two major groups of drug abusers are hard drug addicts and alcoholics. Pulmonary disease and hepatic dysfunction are common in both groups. Choice of anesthetic agents for drug abusers centers around associated illnesses and their severity. The alcoholic often needs vitamin therapy and sedation, but attempting to change drug habits in the face of an acute illness is dangerous. An organized plan of approach is more important than choice of therapeutic agent.


Parietal cell vagotomy without drainage: advantages and clinical applications.

Parietal cell vagotomy (PCV) without drainage for the elective treatment of duodenal ulcer is a safe procedure. All studies are in agreement that there were fewer gastric complaints following this procedure than after any other type of operative treatment. Dumping occurred in 9% and diarrhea in 3% of our 188 patients. The diarrhea and dumping were mild, easily controlled, and not disabling in any patient. The low rate of recurrent ulcer (3%) suggests that PCV is an effective operation. Considerably more follow-up time is required before this highly rational operation for duodenal ulcer can be considered the successful procedure that the present evidence suggests. The operation is relatively easy to perform, but it does require operative finesse and training which are best acquired in an operating room working with a surgeon who has demonstrated good results with PCV. This will spare beginners the disappointment of an unnecessary high failure rate.


Role of tumor immunity in ovarian cancer.

Antigens associated with ovarian cancer tissue have been identified by the use of heteroantisera. It has also been reported that lymphocytes from patients with ovarian cancer responded to phytohemagglutinin (PHA) and keyhole-limpet hemocyanin (KLH) but had failed to respond to autologous tumor extracts. In our series, pretreatment sera from 37 patients with stage III and IV ovarian cancer failed to react with ovarian cancer antigen preparations. After therapy, serum from only three patients was reactive: all three patients were treated by chemoimmunotherapy. Preliminary data from this clinical trial for treating stage III and IV ovarian cancer with chemotherapy, immunotherapy, or combined chemoimmunotherapy show that survival of patients treated by chemotherapy or immunotherapy corresponded to that of nonresponders to L-PAM therapy as described in another study. Interestingly, combined chemoimmunotherapy produced a survival curve depicting significant improvement, similar to that for the responders to L-PAM therapy reported in that study.


Three-year prospective study of carbohydrate metabolism in women using Ovulen.

Twenty-eight women were tested with a standard three-hour oral glucose tolerance test before and after three years of using a combination-type oral contraceptive containing mestranol and ethynodiol diacetate (Ovulen). At the three-year test time there was a significant elevation of the patients' weights and their 1-, 2-, and 3-hour blood glucose and 2- and 3-hour plasma insulin values. Pretreatment control tests had shown no "abnormal" blood glucose curves, whereas at the three-year test 17.2% of the curves were "abnormal". Serial follow-up studies in two women after stopping the medication showed that the abnormal glucose curves reverted to their pretreatment status within 12 months.


Coumarin resistance: a diagnostic and therapeutic approach.

Resistance to coumarin anticoagulants in two black patients was established. The resistance appears to be of the pharmacodynamic type since high doses of the coumarin drugs (with accompanying high plasma concentrations) were needed to achieve therapeutic prothrombinemia. A pharmacokinetic mechanism for the resistance was ruled out. This phenomenon has no ethnic uniqueness as exemplified by these cases and two earlier reports. A brief review of the problem is presented, with an approach for establishing the type of resistance and a plan for patient management.


Intraoperative fluid and electrolyte management in the pediatric surgical patient.

A comprehensive plan for intraoperative fluid and electrolyte maintenance in the pediatric surgical patient should be made before the start of anesthesia and carried out carefully but aggressively by the surgeon and anesthesiologist. There must be careful assessment of intraoperative blood loss, accurate calculation of the volume of clear fluids given, and frequent measurement of electrolyte levels, blood gas levels, and hematocrit values, particularly during long operative procedures. Tabulated are maintenance fluid requirements, suggested fluid replacement schedules, and formulas for determining blood volume and allowable blood loss, plus a regimen for blood replacement.


Hyporegenerative anemia in primary hyperparathyroidism.

A series of patients with primary hyperparathyroidism showed a high incidence of anemia. Red cell morphology and indices, iron, folate and B12 were generally normal and reticulocyte counts inappropriately low. Focal fibrosis of the marrow space was observed in marrow biopsies from two patients, but no patient showed overt signs of a myelophthisic process. Anemia tended to occur in those with more severe hyperparathyroidism (higher serum calcium level or radiographic osteitis fibrosa cystica). Since severe hyperparathyroidism frequently compromises renal function, it is not always clear whether the anemia should be attributed to renal failure or to the metabolic disease. In nine of the 24 anemic patients, however, renal function was normal. Hyperparathyroidism may cause a hyporegenerative anemia, the mechanisms for which have not been elucidated.


Use of water in the examination of the upper gastrointestinal tract.

Described is an original technic in which water is used in conjunction with the barium examination of the upper gastrointestinal tract. After the routine barium examination, the ingestion of water through a straw with a hole in it, while the patient is upright, results in a triple-contrast study of the stomach. The technic has proven useful in: (1) demonstrating all types of benign and malignant lesions in the stomach, pyloric valve, and duodenum; (2) showing benign and malignant lesions, inaccessible to palpation, in the fundus and upper portions of the stomach body; (3) demonstrating "occult" ulcers when the water washes away all of the barium except that which for some unknown reason remains within the ulcer crater; (4) examining the postoperative stomach, particularly when marginal ulceration is suspected after subtotal gastrectomy; and (5) demonstrating hiatal hernias and gastroesophageal reflux. A modified technic is used for patients who can only be examined in the recumbent position.


Nature and significance of colonic polyps.

The concept of inevitable premalignancy in all adenomatous polyps of the colon was challenged as early as 1958, and since that time much debate has centered about the malignant potential of adenomatous polyps of the colon. Current thinking indicates that the majority of colonic polyps fall into one of four categories: hyperplastic, villous adenoma, adenomatous, and villoglandular. Analysis of the present series of 387 colonic polyps removed endoscopically indicates that the villoglandular group has a notable malignant potential, and that the pure adenomatous polyp probably carries a minimal malignant threat. The present series does not challenge the accepted concept that hyperplastic polyps are of no malignant potential, and that villous adenomas are quite frequently malignant at the time of diagnosis.


Papillary adenocarcinoma of a thyroglossal duct cyst.

Carcinoma in thyroglossal duct tissue is a rare occurrence. A case of papillary adenocarcinoma in a thyroglossal duct cyst is presented. Local excision by the Sistrunk technic appears adequate for the noninfiltrating, nonmetastatic lesion. Thyroid hormone should be given as a suppressive agent. Continuous follow-up is necessary for the rest of the patient's life.


Acetohexamide hypoglycemia: treatment by peritoneal dialysis.

Acetohexamide hypoglycemia in a patient with renal failure has been successfully treated by peritoneal dialysis. Peritoneal dialysis was done in such a patient, and specimens of serum were collected to measure levels of acetohexamide and its main active metabolite, hydroxyhexamide. During dialysis, hypoglycemia was corrected. After 17 1/2 hours of dialysis, serum acetohexamide level was essentially unchanged. Serum hydroxyhexamide level had decreased at a slower rate than the rate of decrease previously measured in a uremic patient not on dialysis. Although peritoneal dialysis may correct the hypoglycemia, the data suggest that acetohexamide and hydroxyhexamide are not dialyzable. Due to these problems this drug should not be used in patients with chronic renal failure. The drug of choice to control hyperglycemia in patients with renal insufficiency is insulin. If for any reason insulin cannot be used, tolbutamide is the oral hypoglycemic agent of choice.


Profound neutropenia caused by oxacillin.

An instance of profound neutropenia secondary to oxacillin which resolved rapidly on withdrawal of the drug was reported. It was accompanied by eosinophilia. Although the bone marrow findings were indicative of destruction of granulocytes in the periphery, antibody could not be demonstrated.


Thyroglossal duct cysts in the elderly.

An instance of thyroglossal duct cyst in a 68-year-old man was reported. The clinical diagnosis of a thyroglossal duct cyst is suggested by the presence of a cystic mass situated anteriorly in the midline of the neck regardless of the patient's age. A review of the literature revealed that the incidence markedly decreases with age, with the great preponderance of cases occurring in infancy and childhood. Fourteen cases of thyroglossal duct cyst have been reported in the over-60 population.


Biliary tract surgery.

Postoperative wound infection rates after biliary tract surgery vary tremendously from 2% after uncomplicated cholecystectomy to 20% in series including many jaundiced patients. Almost all such infections arise from organisms growing in the diseased biliary tract, since infection rate of 1% are achieved when the bile is sterile. A history of cholangitis identifies only one third of the patients with infected bile, but four easily recognized clinical factors point to positive bile cultures in 60% to 75% of patients: (1) age over 70, (2) obstructive jaundice, (3) common duct stones without jaundice, and (4) emergent acute cholecystitis. These selected high-risk patients have postoperative infection rates of 20% to 27%. Preoperative administration of cephaloridine reduced this high rate of infection to 5% in a prospective randomized but not blinded trial. The initially reported experience of 84 patients has been extended to 140 and continues to confirm the efficacy of prophylactic antibiotics in selected high-risk patients. In contrast, there is no present evidence supporting the use of antibiotic prophylaxis in low-risk patients under 70 years of age undergoing uncomplicated cholecystectomy.


Infection surveillance: identifying the problems and the high-risk patient.

A prospective wound surveillance program (47,917 wounds studied) proved valuable in determining the factors responsible for infection, the operations at risk, and the influence of variables. Because the rate of infection in clean wounds is the most sensitive indicator of surgical technic, it is a useful method of quality control.


Vaginal hysterectomy.

The role of antibiotic prophylaxis in women undergoing vaginal hysterectomy is reviewed. Although there has been a wide range in the reported incidence of postoperative infection and a wide variation in the definition of infectious morbidity, all of the reported studies to date have shown a decrease in the number of infections with this regimen. Currently, a short perioperative course with the cephalosporins is recommended for patients not allergic to penicillin, and this continues to be effective. A short alternative regimen for the penicillin-allergic patient has not been studied as yet.


Joint replacement.

Joint replacement at the Hospital for Secial Surgery has shown that the procedure of cementing total hip replacement components in place carries a high risk of infection. Simple preventive measures against infection are essential, including careful identification of patients at special risk, preoperative eradication of all possible foci of infection, and strict observance of high-quality operative technic. The risk of infection and the disastrous consequences of infection when it occurs justifies the use of perioperative bactericidal-antibiotic prophylaxis against gram-positive organisms in patients undergoing total joint replacement. Studies of the 1,350 patients having total hip replacement in a four-year period, with minimal follow-up of two years while on a preventive program of this kind, show that the regimen as used at the Hospital has been effective and devoid of important harmful side effects.


Microbiologic basis for the rational use of prophylactic antibiotics.

Appropriate use of antibiotics is enhanced by the effective application of data on antimicrobial susceptibility. A number of methods are currently available for routine determination of susceptibilities, including agar dilution, broth dilution, agar diffusion, and several semiautomated methods. If susceptibility testing is properly done, it can serve as the basis for the generation of statistical data of use to the clinician. Periodically updated tables detailing the antimicrobial susceptibilities of commonly isolated organisms enable the physician to make appropriate choices of antibiotics for prophylaxis and for the initial treatment of serious infections, before the susceptibilities of the infecting organisms are known. With computer assistance, it is possible to use susceptibility data for quality control and for more sophisticated epidemiologic purposes. For the past several years, we have studied a number of potential uses of computer-generated data at the Massachusetts General Hospital. Several of these applications, especially as they might relate to the prophylactic use of antibiotics, are discussed in this paper.


Pathology of aortic valve replacement.

The autopsy findings in 41 patients with University of Cape Town aortic valve prostheses were studied. Twenty patients died within 1 month of operation and 21 patients died later, up to 141 months after operation. The most important postoperative complications which were common to both groups of patients were arrhythmias, myocardial failure and infection. Systemic embolism was the most important late complication. The type of coronary arterial perfusion or ventricular rhythm during bypass did not influence the myocardial pathology. Patients who died of myocardial failure did not show more severe myocardial alterations than did those who died of other causes.


The effect of prolonged isolation from environmental allergens on the clinical and laboratory manifestations of the allergic state. Observation on members of the South African Antarctic expedition.

The 1975 South African Antarctic expedition included 8 men with a history of allergy, 7 who showed cutaneous hypersensitivity to common allergens, but denied having experienced symptoms, and 6 who had neither symptoms nor positive skin tests. During a year of residence in the essentially allergen-free, barren environment of Antarctica, allergic subjects were entirely sypmtom-free. Prolonged isolation from environmental allergens did not consistently diminish the serum concentration of total or specific IgE or the intensity of positive skin test reactions, which indicates that the cells responsible for the synthesis and secretion of reaginic antibodies have a prolonged existence and do not require repeated allergenic stimulation for maintenance of function.


Persistent ventricular ectopic beats: a long-term study.

Electrocardiograms of 8 000 flying personnel, who had been undergoing routine medical examinations from 1963 to 1976, were analysed for the presence of ventricular ectopic beats (VEB). Those in whom VEB persisted, i.e. VEB of the same form recorded in two or more tracings taken at least 1 year apart, were carefully examined for the presence of cardiovascular disease and followed up. VEB were detected in 178 (2,2%) of the 8 000 subjects. Of the 98 subjects followed up after VEB had been detected, 54 (55%) showed persistence of this arrhythmia. Significant cardiovascular disease, i.e. ischaemic heart disease, hypertension or atrial fibrillation, developed in 15 (27%) of these subjects at some time during the study. No instances of sudden death occurred over a mean follow-up period of 8,3 years, even though complex (multiform, repetitive or alternating) VEB were recorded in 20 (37%) of the 54 subjects.


Ankylosing spondylitis in three Zulu men negative for the HLA B27 antigen.

Three cases of ankylosing spondylitis in Zulu men are presented. They are of interest in that all 3 patients were negative for HLA B27, a tissue-typing antigen that is present in the vast majority of Caucasians with the disease. We draw attention to the rarity of ankylosing spondylitis and also of the B27 antigen in Blacks and offer some postulates on the relationship between these two phenomena.


Bile peritonitis and miliary tuberculosis: a case report.

We report an unusual case of bile peritonitis in a child. The literature on bile peritonitis is reviewed, and its treatment is discussed. According to the literature, bile peritonitis has a good prognosis provided operation is early. Patients in whom bile is septic at the time of surgery have an increased morbidity and a considerable mortality.


Adenomammectomy.

Adenomammectomy is an operation for the removal of the glandular element of the female breast with the ultimate goal of reconstruction by prosthesis, by autogenous tissue, or by a combination of the two. Indications, technique, and complications are discussed.


Recidivism among patients with gonococcal infection presenting to a venereal disease clinic.

We studied the incidence of gonorrhea, gonococcal recidivism and related factors in venereal disease clinic patients. A sample of 2029 records, which were selected randomly, were reviewed. Gonorrhea and gonococcal recidivism were more common in nonwhite patients, particularly in nonwhite men. Gonorrhea occurred more than once in 23% of the patients with gonorrhea and those patients accounted for 48% of all cases of gonorrhea. We also interviewed 627 new patients attending the venereal disease clinic. Gonococcal recidivism was reported more often by older men and younger women. Use of contraceptives was less frequent among white women who were gonococcal recidivists. However, contraception was not used by 40% of the patients or their partners. Gonococcal isolation rates were lowest in men who used condoms. The number of sexual partners did not correlate with age, use of contraceptives or results of cultures for gonococci. Men had more sexual partners than women and white women had more partners than non-white women. Nine percent of patients took oral antibiotics prior to their visit to the clinic; antibiotic ingestion did not correlate with the patients' race or the results of their cultures.


An evaluation of trichomoniasis in two ethnic groups in Papua New Guinea.

Different population groups in Papua New Guinea were examined for infestation with Trichomonas vaginalis. Melanesian women (44.6%) were more likely to be infected than Caucasian women (14.2%). Similarly, Melanesian men (10.9%) had a higher prevalence of infection than Caucasian men (0%). Among the women, infection with T. vaginalis was also correlated with increasing age, parity, and place of residence.


Results of jejunoileal bypass in two hundred patients with morbid obesity.

Two hundred massively obese patients were submitted to four variations of jejunoileal bypass during the last decade. The operative mortality rate was 2.5 per cent. Nonfatal postoperative complications occurred in patients who had the small intestine shortened to 18 to 20 inches by end-to-end jejunoileostomy. In follow-up periods up to ten years, there have been nine late fatalities, five of which were unrelated to jejunoileal bypass. Despite late complications which have included renal stones, enterohepatic syndrome and ventral hernia, 66 per cent of the survivors have achieved good results by the criteria used. Metabolic improvements include a profound and sustained reduction in plasma concentrations of cholesterol and triglyceride.


A critical reappraisal of Dukes' classification.

The aim of this survey has been to stress the need of a uniform classification of tumor spread. This requires a standard procedure for processing the surgical specimens. An international standardization would permit a more objective comparison of the results of treatment and survival of carcinoma of the colon and rectum in different clinics.


Optimal size of resection margin for thin cutaneous melanoma.

The width of the resection margin for 62 melanomas less than 0.76 millimeter thick ranged from 0.10 to 5.50 centimeters, with 32 per cent being 1.0 centimeter or less. None of these patients has a local recurrence or metastases develop. It appears that these thin tumors should be treated conservatively, the size of the resection margin being dependent upon the anatomic location of the tumor. In most instances, skin grafting should not be necessary.


Experience with a urinary sphincter prosthesis.

From February 1974 through April 1975, ten patients have had a Scott urinary sphincter prosthesis implanted for the relief of urinary incontinence. In nine of the patients, incontinence was due to trauma of the sphincter, and in one patient, incontinence was due to a neurogenic bladder. Four patients have been totally continent following operation and, thus far, have not required additional operative procedures. Two additional patients were continent after the initial implant, but incontinence recurred because of mechanical failure of the device. Both patients are again continent following replacement of the defective portion of the prosthesis. Four patients have been classified as failures. Infection was the cause of failure in three of these patients, and in the fourth patient with a neurogenic bladder, failure was due to uncontrollable detrusor hyperreflexia.


Replacement of the peritoneum with amnion following pelvic exenteration.

An analysis was made of 24 patients undergoing pelvic exenteration. By chance, the patients are divided into two groups, 12 having the pelvic floor treated by the traditional means and 12 in whom amniotic membranes have been used. A statistically significant shortening of the hospital stay was experienced by those in the amnion group with a total lack of intestinal complications being related to the raw surface of the pelvis. A large number of recurrent or de novo carcinomas of the vagina following carcinoma of the cervix treated with radiation are identified. Two deaths in this series were related to complications of the small intestine.


Preoperative localization of adrenal remnants.

Patients with recurrent Cushing's syndrome after bilateral adrenalectomy should have an adrenal scan prior to any attempt at repeat laparotomy. In those patients with a localized remnant on the adrenal scan and no evidence of a tumor of the pituitary gland, unilateral exploratory laparotomy should be considered for removal of the remnant. In our series of five patients fulfilling the aforementioned criteria, we have been successful in terminating the recurrence of Cushing's syndrome in these patients.


Reversibility of ischemically induced mitochondrial dysfunction with reperfusion.

To clarify the reversibility of ischemically induced mitochondrial dysfunction, a murine model of hepatic ischemia was used. Following 60 minutes ischemia to one hepatic lobe, significant alterations in mitochondrial, energy-linked metabolism were apparent. After the ischemic episode, 30 minutes of reperfusion resulted in partial restoration of mitochondrial function with succinate but not alpha-ketoglutarate as substrate. Lactate accumulation was also partially reversed with reperfusion. Histologic examination subsequent to the ischemic episode revealed development of partial necrosis in nine of ten ischemic lobes. alpha-Ketoglutarate oxidation is more sensitive to injury than succinate oxidation. With proper choice of substrate, measurement of mitochondrial function just after an ischemic insult may predict subsequent hepatic failure due to cellular necrosis.


Morbidity and mortality of renal exploration for cyst.

Surgical exploration for a renal mass is a procedure associated with a low mortality and morbidity, even in a population with a median age of 58 years, most of whom were listed according to the American Society of Anesthesiologists as class II or greater. As a consequence, the procedure warrants serious consideration as a diagnostic measure. Nonsurgical diagnostic procedures are associated with less immediate risk to the patient but with less immediate risk to the patient but with more limited accuracy. The decision as to which methods of evaluation to use in each particular patient must be individualized. The general and related symptoms, physical and laboratory findings and the quality and results of roentgenography and puncture studies of the patient warrant consideration in recommending a reasonable course. Whatever procedures are recommended, the patient should be adequately informed to recognize that alternative treatment approaches are available.


An improved radioimmunoassay for 4-androstene-3,17-dione.

A radioimmunoassay using an antiserum produced against 6beta-hydroxy-4-androstene-3,17-dione-6-succinyl-BSA conjugate is described which permits the rapid determination of 4-androstene-3,17-dione in multiple serum samples that are purified by column chromatography on neutral alumina. Steroids which reacted significantly with the antiserum were found to be 5alpha-androstane-3,17-dione, 5beta-androstane-3,17-dione, and 6beta-hydroxy-4-androstene-3,17-dione. After column chromatography on alumina, however, the only significantly cross-reacting steroids were the 5alpha and 5beta-androstane-3,17-diones, while cross-reactivity from other steroids was reduced to less than 1%.


Radioimmunological determination of urinary tetrahydroaldosterone.

A method is presented for radioimmunological determination of 3alpha, 5beta-tetrahydroaldosterone. It is based upon the reactivity of this steroid with an antiserum induced by the 3-carboxymethyloxime of 18, 21-aldosterone diacetate conjugated with bovine serum albumin. One hundred microliters of urine enzymatically hydrolyzed with an helix pomatia preparation, containing tritiated tetrahydroaldosterone for the yield calculation, were extracted with dichloromethane and chromatographed on a small celite column. The yield after extraction and chromatography was 64 +/- 17%. The radioimmunological determination was carried out in a conventional manner. The method is specific, sensitive (10 pg/tube), exact, reproducible, very simple and extremely rapid. The results showed good agreement with values given by a colorimetric method (p less than 0.001). The median value measured in 45 healthy adult subjects under standard sodium diet was 53.3 microgram/24h (95 % of the population within a 16.6 to 131.1 microgram/24h range). In 78 cases of adrenocortical insufficiency, 60 cases of obesity and 28 cases of hypokalemia, the median values (and the ranges : microgram/24h) were respectively 7.7 (1.0 - 51.0), 80.9 (17.0 - 503.0) and 64.3 (8.0 - 181.0). In 330 hypertensive patients the excretion of tetrahydroaldosterone exceeded the normal range in 115 cases (35%) with a median of 199.7 microgram/24h (131 to 620 microgram/24h).


Progesterone in the uterus. VIII. Uptake of corticosterone and incorporation of progesterone under concurrent injection of corticosterone into rat uterus.

A study of the subcellular distribution of radioactivity in rat uterus after injection of labelled corticosterone showed that the radioactivity was observed in all fractions from 5 min. to 120 min. A maximum uptake was observed 10 min. after application of the labelled steroid. Competitive uptake of radioactive progesterone and unlabelled corticosterone was assayed 10 min. after injection of the hormone mixture. The ratio between radioactive progesterone and unlabelled corticosterone was 1:1 and 1:2 (moles:moles), respectively. Compared with control experiments with rats which had received radioactive progesterone alone, the results gave evidence that progesterone found in all subcellular fractions and in the total homogenate was not depressed by unlabelled corticosterone. However, unlabelled progesterone reduced the tritiated progesterone in uterine tissue. This observation demonstrates that the uptake of progesterone by rat uterus is specific.


In vitro steroid metabolic studies in human testes I: Effects of estrogen on progesterone metabolism.

A technique of incubation of testicular tissue in vitro with radiolabeled precursors was applied in the investigation of the steroid biosynthesis by testes of four young men after long-term, high-dose estrogen treatment. A positive correlation between plasma and testicular steroid levels, and in vitro capacity of the testes to metabolize progesterone was demonstrated. Estrogen administration produced a very significant inhibition of plasma and testicular levels of testosterone. The in vitro synthesis of testosterone from progesterone was very severely impaired; especially 17alpha-hydroxylation of progesterone. 20alpha-hydroxysteroid-dehydrogenase activity was found to be increased after estrogen treatment, both in vivo and in vitro. These findings suggest that testicular 17alpha-hydroxylase activity (and possibly also 17-20 lyase activity) is either under gonadotropin regulation, or is directly suppressed by estrogen. This could result by decreased enzyme synthesis, direct enzyme inhibition or affectation of the cofactors or cytochromes necessary for the enzymatic activity. 20alpha-reduction of C21-steroids would represent an alternative pathway for their catabolism, not regulated by gonadotropin or not affected by estrogen, that would be significant in situations with reduced 17alpha-hydroxylase activity.


Sensitive radioimmunoassay for digoxin in plasma and urine.

A reproducible and sensitive radioimmunoassay for digoxin in either serum, plasma or urine is described. Using 0.5 ml of serum or plasma, the assay sensitivity is 0.05 ng of digoxin/ml. The antiserum and tracer solutions employed are available in a kit sold in the United States. All other reagents were prepared in the laboratory. The assay allows measurement of digoxin in plasma or serum for 96 hours after single 0.5 mg doses of digoxin; this is necessary in human bioavailability studies to accurately estimate the total area under the digoxin concentration, time curve from zero to infinite time. In contrast, with the kit assay, employing 0.2 ml of plasma or serum, it has been reported that the 12 hr serum digoxin levels, after single 0.5 mg doses, are, in most subjects, below the sensitivity limit (about 0.5 ng/ml) of the assay.


Marine sterols. VII. Synthesis of patinosterol, a minor constituent of sterols of the scallop, Patinopecten yessoensis.

The structure of patinosterol, a minor sterol from the scallop, Patinopecten yessoensis, was established as 22-trans-27-nor-(24S)-24-methyl-5alpha-cholest-22-en-3beta-ol by synthesis through Wittig reaction.


Steroids and related products. XLIII. The synthesis of 17-hydroxymethylprogesterone.

The synthesis of the first 17-hydroxymethyl analogue of a steroid hormone of the progesterone-corticoid group, 17-hydroxymethylprogesterone, is described. The starting material for its preparation was 3alpha,12alpha-diacetoxy-5beta-pregnan-20-one and the 17-hydroxymethyl structure was developed by functionalization of the 17-methyl group of a 17alpha-methyl etio ester by a Barton reaction. Neither 17-hydroxymethylprogesterone nor its acetate shows appreciable progestational activity in the Clauberg-McPhail assay.


Synthesis of pyrogallolestrogens (2,3,4-trihydroxy-1,3,5(10)-estratrienes) and their methyl ethers.

The preparation of 2,4-dihydroxyestrone, 2,4-dihydroxyestradiol-17beta and their methyl ethers (14 compounds) is described. The structures were established by nuclear magnetic resonance, infrared and mass spectra as well as by elemental analyses, microchemical reactions, alternative synthetic routes and by their chromatographic properties.


Testosterone synthesis in vitro by the fetal testis of the guinea pig.

Synthesis and secretion of testosterone by testes of guinea pig fetuses were studied in organ culture. The amount of testosterone secreted into the culture medium was estimated by radio-immunoassay. It was demonstrated that testosterone was already secreted by testes explanted at 25 days. The amount of testosterone secreted during the first day in culture by testes from fetuses of different ages (25-30 days) increased with fetal age. The amount of testosterone extracted from fetal guinea pig testes at ages used for explantation (25-30 days) were much lower than the amount secreted during the first 24 hours in culture. During subsequent days in culture, an increase in the amount of testosterone secreted was observed only for testes explanted at 25 days. The amount secreted by testes from older fetuses (26-30 days) stayed constant or decreased. Aminogluthetimide phosphate (100 micron) decreased significantly testosterone secretion by testes explanted at 25 days. These findings indicate that the capacity for biosynthesis of testosterone is present in fetal guinea pig testes at 25 days and increases during the subsequent days.


Errer rate, precision, and accuracy in immunohematology.

Quality control in the blood bank has traditionally been concentrated in the areas of reagents, equipment, and components. We have found that it can be extended to the measurement of error rate, accuracy, and reproducibility as well. We propose the use of a "correction rate" as a correlate of actual error rate, since numbers of errors in final ABO interpretations are infrequent and difficult ot accumulate. We have measured accuracy as the frequency of false positive anf false negative results, using weakly active antibodies both in the test situation and in actual practice. Finally, reproducibility can be measured with a series of coded duplicate samples covering the range of immunohematologic reactivity. By using these methods, a laboratory can regularly measure error rate, accuracy, and reproducibility as part of its quality control program.


A simplified procedure for deglycerolizing red blood cells frozen in a high glycerol concentration.

Although the high (40 to 50 per cent) glycerol method of freezing red blood cells has many advantages, no feasible procedure for deglycerolizing with only a clinical centrifuge has been available. Thus this method has been restricted to blood centers that distribute a sufficient number of frozen cells to warrant the installation of automated cell washing equipment. However, by sedimenting the glycerolized cells prior to freezing and discarding the excess glycerol solution, postthaw deglycerolizing can be simplified to consist of an initial double dilution with hypertonic NaCl and isotonic saline-glucose followed by two cycles of sedimentation and resuspension in isotonic saline-glucose. The method is applicable to units frozen either at -80 C or in liquid nitrogen vapor. Units frozen in this way can also be deglycerolized in commercial automated cell washers using suitably modified protocols.


Evaluation of a large-scale frozen blood program.

The characteristics of previously frozen red blood cells, prepared in a large-scale frozen blood program using the Red Cross method were evaluated. The use of the method as originally described resulted in approximately 91 per cent freeze-thaw-wash recovery of red blood cells. When the glycerolization step was modified by adding the partially glycerolized erythrocytes into 300 ml of 6.2M glycerol, freeze-thaw-wash recoveries were decreased. However, gradient addition of glycerol to the red blood cells without the use of stylet, resulted in acceptable in vitro recoveries. Thawing frozen units in waterbath, to which no antiseptic was added, could introduce bacteria into units of previously frozen red blood cells. Therefore, it seems advisable to use dry heat thawing procedures. Previously frozen red blood cells prepared in the large scale maintained normal levels of ATP and 2,3 DPG. Therapeutic transfusions had acceptable 24-hour survival in vivo.


Ultrafiltrable adenosine triphosphate and 2,3-diphosphoglycerate concentrations in cold-stored human erythrocytes.

Free ATP and DPG concentrations in ACD-preserved human erythrocytes (rbc) were estimated by measuring these organic phosphates in ultrafiltrates of cell lysates prepared at 0 to 2 C. The free ATP concentration in hypotonic hemolysates decreased from 0.59 to 0.08 mumol/ml rbc during four weeks of cold storage. In French Pressure Cell lysates, free ATP increased from 0.23 to 0.47 mumol/ml rbc in the first week and then declined to 0.12 mumol/rbc during the following three weeks. In two weeks, the free DPG level decreased from 0.64 to 0.41 mumol/ml rbc in hypotonic lysates and from 1.08 to 0.15 mumol/ml rbc in French Pressure Cell lysates. It is proposed that, as total DPG concentration decreases during cold storage, free ATP concentration also decreases due to increased ATP binding to hemoglobin sites vacated by DPG. It is suggested that it is the change in the free rather than the total ATP which may be more relevant to the metabolism of the cold-stored erythrocyte.


Consequences of prior alloimmunization during granulocyte transfusion.

The transfusion of leukocyte-containing blood products can lead to the production of antibodies to antigens on the surface of leukocytes. Such antibodies can be detected by a variety of techniques including assays for lymphocytotoxicity, granulocytotoxicity, and leukoagglutination. In order to evaluate the effect of preformed anti-leukocyte antibodies during granulocyte transfusion therapy, recipient beagles were sensitized to donor foxhound antigens. After being made granulocytopenic with cyclophosphamide, these animals were transfused with a set dose of granulocytes collected by continuous flow centrifugation. When compared to the results of similar transfusions to nonsensitized recipients, granulocyte transfusions to animals with preformed anti-leukocyte antibodies resulted in lower one-hour posttransfusion leukocyte increments (p less than .04) and in less migration of neutrophils through a skin abrasion into a chamber containing a strong chemoattractant, autologous serum (p less than .0001). Also, profound thrombocytopenia was found in sensitized animals, but not in nonsensitized recipients, one hour after the granulocyte transfusion.


Military blood banking: blood transfusion aboard a Naval hospital ship receiving multiple casualties in a combat zone, a controlled medical environment.

The materials, methods, and policies used in the Blood Transfusion Service aboard the USS Sanctuary (AH-17) during military operations off South Vietnam to transfuse multiple casualties are outlined. Materials and methods common to any blood bank were used with some modification to meet specific requirements. During the period 10 April 1967 to 1 May 1971, approximately 32,000 units of blood were recieved, and over 2,890 severely injured patients were transfused. The policies and techniques used enabled efficient and safe management of blood transfusion for these patients. These methods should be applicable in solving some of the problems which arises as a result of combat operations and civil disasters. A controlled medical environment is described.


An empirical approach to projecting regional blood need.

An empirical mathematical model was developed for projecting monthly and yearly regional blood utilization. Based upon 1974 data from eight Clark County, Nevada hospitals offering a total of 1,389 medical-surgical, and pediatric beds, an unadjusted projection deviated minus 7.2 per cent from the actual 1975 regional blood utilization. Adjusted projections, modified by an averaging technique that utilized previous month's blood utilization along with historical utilization data, resulted in an annual projection that deviated minus 1.9 per cent from the actual blood use. The adjusted monthly mean projection did not differ significantly from the actual mean monthly blood use. This approach appears to be of value in regional planning for long- and short-range blood needs.


Microaggregate content and flow rates of packed red blood cells.

Platelet rich red cells (PRRC) and platelet poor red cells (PPRC) are both prepared in the course of red cell production. PRRC tend to have a higher hematocrit (82 +/- 7) than PPRC (77 +/- 5), (p less than .001). There are more microaggregates present in PRRC (2.48 +/- 1.41 gm) than in PPRC (1.46 +/- 0.61 gm), (p less than .001). The infusion rate for PRRC was 4.0 X 1.8 ml/minute, and this was significantly smaller than for PPRC which was 9.7 +/- 1.7 m/minute, (p less than .001). This compares to a rate for whole blood of 32.8 ml/minute. The difference in flow rate of the two types of red blood cells is in part due to a difference in viscosity, but more inportantly due to a difference in microaggregate content. Flow rate is normalized for both types of packed cells by the addition of 100 to 150 ml of saline, while infusion time is normalized by the addition of only 50 to 100 ml of saline to the packed cell units.


Chronic liver dysfunction in multitransfused hemophiliacs.

Liver dysfunction and exposure to the hepatitis B antigen were assessed by serum transaminase (SGPT and SGOT) levels and HBsAg and anti-HBs during a three year period in a group of 118 patients with factor VIII or factor IX deficiency. The 107 HBsAg negative patients were divided into four groups according to their mode of therapy. Persistently abnormal transaminase values were present in 51 per cent of patients with a large exposure to factor VIII concentrates, in 43 per cent with a small factor VIII exposure and in 37 per cent exposed to prothrombin complexes. This was contrasted with abnormalities in 8 per cent of patients treated only with cryoprecipitate. The incidence and degree of serum transaminase abnormality appeared independent of a past history of jaundice. All patients without persistent antigenemia who had been treated with pooled plasma products showed antibodies to HBsAg. High titer anti-HBs prior to initial fraction therapy appeared protective against jaundice. The eleven patients with persistent antigenemia had significantly higher transaminase levels than the HBsAg negative group.


Failure of postfiltration leukapheresis plasma to increase granulocyte yields.

Autologous plasma collected either during or immediately after continuous flow filtration leukapheresis (CFFL) was infused prior to subsequent donations in an attempt to induce granulocytosis and to augment granulocyte yields. Granulocytosis did not occur in the 15 to 20 minutes following plasma administration and no increase in granulocyte yields could be demonstrated. In addition, the plasma infusion did not affect the timing or magnitude of the transient granulocytopenia which characteristically occurs during CFFL. Although infusion of postfiltration leukapheresis plasma does not appear to feasible or practical means of enhancing granulocyte collection, it may still serve as a valuable tool in the study of granulocyte kinetics.


Evaluation of liquid scintillation counting solutions for radioimmunoassay of hepatitis-associated antigen (HBsAg).

Liquid scintillation counting solutions for radioimmunoassay of hepatitis associated antigen (HBsAg) are evaluated and discussed. Data is also presented which indicates that liquid scintillation counting could be carried out by placing cut-off Ausria-125 test tubes in counting vials containing 10 ml of either Brays, Unogel, or Instagel solutions. The data suggest that Brays was the least effective and Unogel and Instagel were the most effective liquid scintillation counting solutions. This is a fundamental consideration if a laboratory is contemplating an initial investiment in counting equipment. The acquisition of a liquid scintillation counter provides additional capabilities for the clinical laboratory interested in radioisotope measurements. In addition, if a laboratory already has a liquid scintillation counter (Beta counter), the director of the clinical laboratory may elect not to purchase additional counting equipment (gamma counter) since he already has the added advantage of measuring iodine-125 with the Beta counter. The authors propose liquid scintillation (RIA) as an alternative counting system for HBsAg detection in hospital patients and donors.


Large scale preparation of leukocyte concentrates and further purification of lymphocytes and granulocytes with the IBM 2991 cell processor.

A procedure is described for the large-scale production of pure suspensions of human lymphocytes and granulocytes. Platelet-poor buffy-coats, obtained by centrifugation of six units of ABO-compatible ACD blood, were pooled and centrifuged again, resulting in a crude leukocyte concentrate containing approximately 60 per cent of the original amount of leukocytes. Further fractionation of such crude leukocyte concentrates was achieved by scaling up Bøyum's Ficoll-Isopaque density gradient technique with the aid of an IBM 2991 blood cell processor. In this way 2.9 +/- 0.3 X 10(9) mononuclear leukocytes, consisting of 90 +/- 0.7 per cent lymphocytes and 5.3 +/- 0.3 X 10(9) polymorphonuclear leukocytes of 92 +/- 0.7 per cent purity could be isolated in one run. The overall yield was 36 per cent of the original amount of leukocytes.


Autoimmune hemolytic anemia with anti Jka specificity in a patient taking aldomet.

Autoimmune hemolytic anemia (hemoglobin 5.2 g, reticulocyte count 31.0 per cent) developed in a 53-year-old hypertensive woman who was taking Aldomet. Both the patient's serum and the eluate prepared from her red blood cells contained an antibody with anti-Jka specificity. Rapid sustained improvement in the anemia occurred after cessation of Aldomet and a two week course of prednisone therapy. Eight months later, anti-Jka was no longer detectable in the patient's serum and the direct antiglobulin test was nonreactive.


Hemoglobin function in stored blood. XIX. Inosine maintenance of 2,3-DPG for 35 days in a CPD-adenine preservative.

This study establishes that 10 mM inosine is a sufficient additive to maintain 2,3-DPG levels in blood for five weeks of storage in CPD-adenine. No previous experiments were done with CPD-adenine (0.25 mM) using a design which would give statistical proof of the optimal concentration of inosine needed for maintenance of normal hemoglobin function (2,3-DPG) for five weeks of blood bank storage.


Discontinuous flow centrifugation leukapheresis and neutrophil function.

Neutrophils collected by discontinuous flow centrifugation using hydroxyethyl starch were evaluated. Morphology was studied by light and electron microscopy. Functional integrity was assessed by measuring viability, chemotaxis, phagocytosis, and killing power. The harvested granulocytes were morphologically normal and showed no functional impairment.


Immunization against East Coast fever (Theileria parva infection of cattle) by infection and treatment: chemoprophylaxis with N-pyrrolidinomethyl tetracycline.

Cattle were immunized against East Coast fever by the inoculation of a tick-derived stabilate of Theileria parva infective particles and the intramuscular injection, at daily intervals, of n-pyrrolidinomethyl tetracycline at a dose level of 5 mg/kg. Four doses of the tetracycline, starting on the day of inoculation of the infective stabilate, minimised the ECF reactions in the cattle during immunization. Immunity to homologous T. parva stabilate challenge was demonstrated in 27 out of 27 cattle infected and treated in this manner.


Bovine haemoglobin types and their possible relationship to resistance to babesiosis: an experimental study.

Two groups of Droughtmaster cattle, one group previously infected, were challenged with Babesia argentina infected erythrocytes. All animals were typed for haemoglobin and the course of infection followed by regular parasite counts. No conclusive relationship between the frequencies of the HbA and HbB genes and the severity of parasitaemia in the different groups was found. The presence of HbF was not associated with any limitations on the severity of infection in 1 1/2 - 2 1/2 months calves.


Blood typing in disputed paternity cases: capabilities of American laboratories.

This paper summarizes a survey of the blood typing capabilities of representative American laboratories as they are: 1) currently applied to disputed paternity cases and 2) these laboratories potential for utilizing additional tests in disputed paternity cases.


Prevalence of Toxoplasma gondii antibodies in different populations of native Liberians.

An opportunist sero-epidemiological screening of 390 persons during an epidemiologic survey into the distribution of filarial infection in Liberia/West Africa provided data on the distribution of T. gondii antibodies. The average prevalence of antibodies according to the dye-test titers of 1:10 or 1:4 was 45 resp. 58%. After arbitrary division of the total group into regional subgroups there was a rising trend of antibodies with age up to 90% prevalence in the group of coastal residence of origin whereas the prevalence rates remained at a level around 50% in the inland subgroup. The implications of the findings are discussed, but the significance of this observation has to be investigated by a planned study.


A comparison of individual dissection and mass separation for recovery of Onchocerca larvae from vector black flies.

The effectiveness of a mass separation technique, previously used for the extraction of larvae of lymphatic-dwelling filarial worms from batches of vector mosquitoes, was tested as a means of recovering infective-stage larvae of Onchocerca volvulus from Simulium ochraceum in Guatemala. Blood-engorged flies, collected from 10 infected human attractants, were maintained for 9 days to allow ingested microfilariae to develop to the infective stage. The numbers of Onchocerca larvae recovered after groups of these flies were crushed and washed into tissue culture fluid in Baermann funnels was compared with the numbers obtained by individual dissections of flies fed on the same subjects. The mass separation procedure gave a mean recovery rate of 0.03 larva/fly and detected larvae only in flies which had fed on those subjects with the highest microfilarial skin densities. Dissections yielded 0.50 larva/fly (a 16.7-fold increase) and detected larvae in flies collected from all test subjects. The explanation for the ineffectiveness of the mass separation technique may lie in the observed sluggishness of infective-stage Onchocerca larvae and a consequent inability to free themselves from the fly fragments in the Baermann funnel.


[Association between ABO blood groups and fingerprints].

The ABO blood groups and finger prints were studied for a population of 1170 persons (Ukrainians, Kiev). A statistically significant association was determined between these traits which were similar both in men and women. Maximal values of total ridge count and intensity of patients were found in persons with phenotype B, minimal ones, in persons with phenotypes O and A.


Pig production in the Solomon Islands. II. Diseases and parasites.

A study of diseases and parasites of pigs in the Solomon Islands during 1967 to 1969 indicated that infectious diseases were of little consequence. Four arthropod parrasite species were found: one tick, one louse and two tabanids. The tick (Amblyomma cyprium cyprium) was extremely rare. Fifteen species of helminth parasites were recorded and of these Stephanurus dentatus was the most prevalent. All species were identified except a filariid, of which only the microfilariae were seen.


The anti-echinococcosis campaign in Cyprus.

A national anti-echinococcosis campaign was started in 1971, in which education of the public, the control of dogs and the control of slaughter were emphasised. The campaign has already achieved almost total elimination of infection in food animals born subsequent to its initiation. Stray dogs are rare and all others are registered and examined three or four times a year. Infection in dogs has decreased by over 80 per cent (from 6-8 in 1972 to 1-1 in 1976). Legislation governing abattoir functioning and dog control is in force. Violation of legislation is penalised, although the level of awareness of the problem by the public, who co-operate willingly, does not often warrant this.


Tick-borne diseases of domestic animals in northern Nigeria. I. Historical review, 1923-1969.

Information on the occurrence of tick-borne diseases of domestic animals in northern Nigeria for the period 1923 to 1966 is summarised. Due to lack of obvious outbreaks and diverse interest of the veterinary staff, the published information is very scanty. Significant for the period under review was the complicating factor of Babesia bigemina infections in cattle undergoing rinderpest immunisation procedures or suffering from trypanosomiasis. Tick-borne diseases were also considered important in imported breeds of livestock and in those kept under intensive systems of management.


[Electron microscopic study of protoplasts of mesophyll tobacco. I. Ultrastructural and cytochemical study of tobacco protoplasts at early stages of cultivation].

Ultrastructural changes in tobacco mesophyll protoplasts during the first three days of cultvation were studied. Localization of catalase and peroxidase activities in the freshly isolated protoplasts and 2 days after their cultivation was detected by the cytochemical 3,3'-diaminobenzidine method. A conclusion is drawn that the observed changes in the fine structure and localization of the enzymic activity are due to the following processes: reparation of disturbances caused by the isolation procedure, regeneration of the cell wall and rapid dedifferentiation of the initial parenchymatic leaf cells.


Cell-mediated immune response in equine babesiosis.

An intradermal skin test, to demonstrate a delayed cutaneous hypersensitivity reaction in Babesia equi infection in donkeys, was developed. A skin reaction to B. equi antigen was elicited in vaccinnated, infected and carrier intact and splenectomised donkeys. The histopathological examination of the skin biopsy revealed infiltration of mononuclear cells and accumulation of oedematous fluid in the deeper layers of the dermis. A leucocyte migration inhibition test was developed and its specificity as an in vitro measure of cell-mediated immunity to B. equi antigen was established. The results of this study demonstrated a correlation between cell-mediated immunity and protection.


Trypanosomiasis:goats as a possible reservoir of Trypanosoma congolense in the Republic of the Sudan.

Experimental Trypanosoma congolense infections of goats and calves were compared. Goats developed a chronic form of trypanosomiasis, often recovering spontaneously from a strain which caused an acute fatal disease in calves. Goats may be important in the maintenace of T. congolense in nature in the Sudan.


[Ultrastructure of rat adenohypophysis following exposure to several amines of the polymathylene series].

Adenohypophysis ultrastructure was studied under the effect of dicyclohexylamine nitrite and oil-soluble salt of cyclohexylamine used as inhibitors of the atmospheric corrosion of metals. It is stated that even due to the early effect they cause a morphofunctional rearrangement of the organ in spite of the same reaction of the adenohypophysis cells to M-1 and dicyclohexylamine nitrite the effect of the latter causes more distinct and pronounced changes.


[Heterosis, macromolecular composition and several physico-chemical properties of the nucleolar-chromatic complex].

The nucleolar-chromatin complex of the hybrids liver cells is shown to contain a larger amount of RNA and phospholipids. When teeated with 1.0 M NaCl nucleoproteins of hybrid organisms display greater dissociation. A large number of free loci was determined in the matrix when titrating nucleolar chromatin complex with actinomycin "D". The effect of heterosis might be connected with a specific physiochemical state of chromosome in hybrid organisms.


Heartwater in Nigeria. I. The susceptibility of different local breeds and species of domestic ruminants to heartwater.

Investigations were carried out on the susceptibility to heartwater of different species of domestic ruminants available in northern Nigeria. Brown goats originating from Zaria and areas north of it, and Friesian-zebu calves from the Shika Agricultural Research Station, were uniformly and highly susceptible to the disease. Brown goats from southern Zaria showed a variable susceptibility with 64 per cent contracting the disease. Many indigenous cattle and some indigenous sheep were resistant to infection.


The antibody response in sheep vaccinated with experimental Nairobi sheep disease vaccines.

The antibody responses to experimental Nairobi sheep disease vaccines have been assayed. The responses to an inactivated methanol precipitated vaccine were comperable with those following infection with virulent virus. The responses to attenuated vaccines were inadequate to protect against challenge with virulent virus.


Hana Kai II: a 17-day dry saturation dive at 18.6 ATA. I. Objectives, design, and scope.

The dive (Hana Kai II) described in these papers was designed to determine the effects on man of a prolonged exposure to a dry helium-oxygen hyperbaric environment. Comprehensive studies on energy balance, body fluid balance, cardiorespiratory functions, maximal oxygen uptake, psychological performance, and physiological responses to cold were performed at a simulated depth of 580 ft (18.6 ATA) over a 30-day period in March-April 1975. Following a 3-day predive control period at 1 ATA air (period 1), 5 male divers spent 17 days at 18.6 ATA in a helium-oxygen environment (periods 2-6), and returned to 1 ATA air after 7 days of decompression (periods 7-8). They stayed an additional 3 days inside the chamber for postdive control measurements (period 9). The chamber temperature was maintained at 25-27 degrees C during periods 1 and 9, 30-31 degrees C during periods 2-5, and 27-28 degrees C during period 6. At 18.6 ATA, the PO2 and PCO2 of the chamber gas were maintained at approximately 225 and 2 mmHg, respectively. In this introductory paper, physical and physiological characteristics of individual subjects, the major daily activity schedule, and the scope of investigation are presented.


Hana kai ii: a 17-day dry saturation dive at 18.6 ATA. II. Energy balance.

Since previous saturation dives have caused loss of body weight despite apparently adequate-to-high food intake, a complete study of energy balance was undertaken during the saturation dive Hana Kai II. Over a 30-day period in the hyperbaric chamber (3 days of predive control, 1 day of compression, 16 days at 18.6 ATA, 7 days of decompression, and 3 days of postdive control), all food, urine, and feces for five men were analyzed by bomb calorimetry; 24-h energy expenditure (M) was measured from continuous VO2, VCO2, and urine N. Body weight was taken daily; body composition was assessed from density, total body water, and skinfold thickness. Food intake was high throughout the 30 days (about 3500 kcal/day) while fecal and urinary losses were a normal 6-8% of intake. Energy expenditure was increased a little by the hyperbaric condition, but averaged only 2431 kcal/day for the 30 days and yet there was an average loss of adipose tissue of 0.8 kg for each man for the entire period. Nitrogen balance was positive. There was no evidence of heat gain or loss. The energy balance, total fuel compared with energy expenditure, required an additional 919 kcal/man-day for 30 days, an unidentified term which is not measured by conventional techniques.


Hana kai ii: a 17-day dry saturation dive at 18.6 ATA. III. Body fluid balance.

Comprehensive studies on body fluid balance on 5 divers were conducted during the Hana Kai II dive (17 days at 18.6 ATA and 7 days of decompression). Daily urine flow increased from about 2000 ml at 1 ATA to 2600 ml at 18.6 ATA, at 31 degrees C. This diuresis was accompanied by a reduction in urine osmolality (from 650 to 500 mOsm) and a slight increase in osmolal clearance. Endogenous creatinine clearance remained at about 173 ml/min throughout the dive. Despite such a sustained diuresis, neither daily water intake nor total body water volume changed significantly. The plasma renin activity changed little, while both plasma aldosterone concentration and urinary aldosterone excretion increased significantly during the first week at 18.6 ATA. The plasma prolactin concentration showed a significant decrease during the first 3 days at 18.6 ATA. The daily excretion of antidiuretic hormone (ADH) decreased significantly (by 40%) 4 days after compression and remained low throughout the rest of the dive. Insensible waterloss at 18.6 ATA was 35% lower than that at 1 ATA. It is suggested that the observed hyperbaric diuresis is due primarily to suppression of ADH as a result of suppression of insensible water loss.


Hana Kai II: a 17-day dry saturation dive at 18.6 ATA. IV. Cardiopulmonary functions.

Impedance plethysmography was used to measure resting cardiac stroke volume (SV) and thoracic conductive volume (TCV) in four divers at intervals during a prolonged dry saturation dive (17 days at 18.6 ATA and 7 days' decompression). Resting heart rate (HR), blood pressure (BP), and pulmonary minute ventilation (VE) were measured 4 times per day for the duration of the 30-day experiment. The vital capacity (VC) and its subdivisions IC and ERV were measured by spirometry every 3 days. In nonsmokers, VC fell significantly with time (r = 0.64), while VC in smokers increased nearly 400 ml during the first week at pressure before tending to fall with time. Compared to predive, the mean ERV was increased 629 ml at pressure, while VE and respiratory rate were not changed. The increased ERV did not persist postdive and was probably the result of the increased work of breathing a dense gas (4.1 g/liters). Residual volume (RV) measured by nitrogen dilution before and after the dive increased 38% and remained significantly increased (22%) even after one year in 4 divers. It is suggested that hyperoxia (0.3 ATA PO2) combined with increased gas flow resistance caused the VC to fall and RV to increase. The major cardiovascular findings were a transient bradycardia associated with increased stroke volume leading to a significant increase in resting cardiac output associated with an increased rate of rapid ventricular filling, TCV, and BP at depth. Lowering the ambient temperature for 3 days did not re-establish the bradycardia, suggesting that hyperbaric bradycardia is not due to a subtle cold stress.


Hana kai ii: a 17-day dry saturation dive at 18.6 ATA. V. Maximal oxygen uptake.

Cardiorespiratory responses of four men to submaximal and maximal cycling exercise were observed during 17 days at 18.6 ATA. Inspired gas at pressure consisted of hyperoxic (PO2 = 232 mmHg) and normoxic (PO2 = 159 mmHg) helium mixtures with relative gas densities of 3.8 and 2.8, respectively. The average of pre- and postdive VO2max (1 ATA air), which were not significantly different, was 3.10 liters - min-1. During 5 min of submaximal exercise at 50% of VO2max, no significant difference in work rate, VO2, VCO2, VE, respiratory rate, heart rate (HR), stroke volume, blood pressures, or rectal temperature was noted at 18.6 ATA compared to 1 ATA with either gas mixture. Submaximal HR tended to decrease by 5 to 10 beats - min-1 at pressure, and in hyperoxia the VO2/HR ratio was significantly higher. Maximal exercise was performed to exhaustion at work rates requiring about 120% of VO2max. Significant increased in VO2max of 0.10 liter - min-1 (3%) and in endurance time of 2 min (48%) were found during hyperoxic gas breathing, whereas normoxic values at 18.6 ATA were similar to those at 1 ATA. Significant reductions in maximal HR of 8 beats - min-1 (4%) were observed with both gas mixtures at pressure, and VE was significantly decreased by 36 liters - min-1 (26%) in hyperoxia and 29 liters - min-1 (21%) in normoxia. No change was found in the calculated cardiac output. Maximal voluntary ventilation, which was measured only for the hyperoxic gas, fell significantly by 80 liters - min-1 (40%). Results indicate that aerobic power and endurance performance were affected by oxygen pressure. Normoxic work capacity, however, was not decreased at 18.6 ATA, despite marked reductions in HR and VE.


Hana kai ii: a 17-day dry saturation dive at 18.6 ATA. VI: Cognitive performance, reaction time, and personality changes.

Measures of spatial orientation, associative memory, general intelligence, arithmetic ability, reaction time, and personal/social perceptions were administered to five subjects during a 31-day saturation exercise. Performance decrements were noted during 17 days of exposure to hyperbaric Hi-O2 at 18.6 ATA. Significant losses in general intellectual ability were noted, as well as trends toward significant losses in other cognitive tests. Reaction time and arithmetic errors increased significantly during the early testing sessions. Performance during a 3-day cold period was equivocal; arithmetic errors increased, but other measures improved or remained constant. Environmental stressors such as fatigue, anxiety, health problems, personal and social adjustment, and aspects of perceptual deprivation were considered to be influential in reducing performance effectiveness.


Hana Kai II: a 17-day dry saturation dive at 18.6 ATA. VII: Auditory, visual, and gustatory sensations.

Five divers were tested for alterations in auditory, visual, and gustatory functioning during a 17-day saturation exposure to He-O2 at 18.6 ATA. No evidence of permanent hearing loss was disclosed. Critical flicker fusion was not affected, but peripheral visual thresholds were significantly increased during the first two weeks at 18.6 ATA; this was interpreted to be evidence of severe psychological and physiological stress. Foveal vision was unaffected across testings. Magnitude estimation techniques disclosed changes in taste sensitivity, with sweet sensitivity increasing over time and sour sensitivity declining over the course of the dive. Subjects were more sensitive to bitter stimuli at maximum pressure than at sea level, and less sensitive to salt at maximum pressure. The results indicate that appreciable alterations in sensory functioning can occur during saturation exposures, although the sense modalities were differentially affected by such environmental stressors as pressure, psycho-social stress, fatigue, and perceptual deprivation.