Studies of Fructus schizandrae. IV. Isolation and determination of the active compounds (in lowering high SGPT levels) of Schizandra chinensis Baill.

The alcoholic extracts of the kernels of Schizandra chinensis Baill have been reported to be capable of lowering elevated SGPT levels in mice induced by CCl4 and inhibiting the central nervous system. Seven pharmacological active compounds have been isolated from the alcoholic extracts by column chromatography. Five of them are identified as wuweizisu C (I), wuweizisu B (II), wuweizisu A (III), wuweizichun B (IV) and wuweizichun A (V). They are all derivatives of the dibenzo (a, c) cyclooctene system, among which compounds I and IV have hitherto not been reported in literature. Ozonolysis of III and subsequent oxidation with H2O2 yields meso-3,4-dimethyladipic acid. Pyrolytic syn-elimination of V acetate and oxidation of the resultant olefin (V-4) affords a diketone (V-5) with molecular weight of 446. According to these results and based on the NMR spectra, the two methyl groups at C-6 and C-7 of compound I--V must be cis-oriented.


Subjective measurement of high-order aberrations of the eye.

We used an apparatus similar to Tscherning's aberroscope, and analyzed subjects' drawings to obtain the wave aberration surfaces of 55 eyes. This analysis permitted a Taylor series representation of the wave aberrations to terms of the fourth order. The results revealed a wide variety in type and severity of high-order aberrations in which "cylindrical" aberrations were prominent and cases of classical spherical aberrations were rare. We computed the monochromatic modulation transfer function curves for the range of observations. The overall findings suggest a more prominent role for monochromatic high-order aberrations in degrading the visual image than has hitherto been assumed.


Transplanted neural tissue develops connections with host rat brain.

Superior collicular fragments transplanted from fetal to newborn rat brains develop complex internal organization and receive visual afferents from the host providing they lie sufficiently close to the host visual pathways. This system allows investigation in vivo of special affinities between cells of the mammalian central nervous system.


Potential new artificial sweetener from study of structure-taste relationships.

4-(Methoxymethyl)-1,4-cyclohexadiene-1-carboxaldehyde syn-oxime is a new sweetening agent developed by systematic synthesis and taste evaluation of 80 new oximes analogous to the little-used osime sweetener, perillartine.


Cholera toxin-peroxidase: changes in surface labeling of glioblastoma cells with increased time in tissue culture.

Cholera toxin coupled to peroxidase yielded a highly specific ultrastructural marker of plasma membrane monosialogangliosides. Studies with cultures of brain and brain tumors suggested that long-term culture of tissue in monolayers results in eventual loss of surface monosialogangliosides.


The insertion of DNA into vaccinia virus.

Cells infected with vaccinia virus in the presence of hydroxyurea (HU), which blocks DNA replication, were examined in thin sections by electron microscopy at intervals after removal of HU. Dense, fibrillar material was observed at the orifice formed just before closure of the membrane constituting the envelope of the immature form of the virus. It is concluded that synchrony of assembly enabled stages in the condensation and insertion of viral deoxyribonucleoprotein to be observed. The mechanism appears to be similar to that encountered in morphologic studies of herpes simplex virus and in biochemical studies of poliovirus, adenovirus, and several bacteriophages.


Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vitro and in vivo.

Evidence has been obtained that a specific isomer of a diol epoxide derivative of benzo(a)pyrene, (+/-)-7 beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, is an intermediate in the binding of benzo(a)pyrene to RNA in cultured bovine bronchial mucosa. An adduct is formed between position 10 of this derivative and the 2-amino group of guanine.


Cytoplasmic aldo-keto reductases: a class of drug metabolizing enzymes.

Aldehyde and ketone xenobiotic substances are preferentially reduced to alcohols by cytoplasmic enzymes in mammals. These enzymes are widely distributed in the tissues, have broad substrate specificities, have similar physical-chemical characteristics, and require reduced nicotinamide adenine dinucleotide as cofactor for the reductions. These reductases define a system of detoxification for aldehyde and ketone groups.


Histones and G banding of chromosomes.

Polylysine, polyarginine, and histones H1, H2A, H2B, and H3 inhibit Giemsa staining and chromosome banding by binding to DNA and preventing side stacking of the positively charged thiazine dyes to the negatively charged phosphate groups on DNA. This is a nonspecific effect and does not of itself provide evidence for a role of histones in G banding. The question of whether histones are involved in chromosome banding is reviewed.


Calcium release from skeletal muscle sarcoplasmic reticulum: site of action of dantrolene sodium.

The muscle relaxant dantrolene sodium acts directly and specifically on skeletal muscle, unlike other pharmacological agents which affect the central nervous system or act at the nueromuscular junction. Dantrolene sodium markedly suppresses the release of calcium previously sequestered by skeletal, but not cardiac, muscle sarcoplasmic reticulum. No effect in the total amount of calcium accumulated was found. In situ, the drug may reduce the amount of calcium necessary for muscle contraction.


Photochemotherapy: identification of a metabolite of 4, 5', 8-trimethylpsoralen.

A compound, 4, 8-dimethyl, 5'-carboxypsoralen (DMeCP), has been identified in mouse urine as a major metabolite of the photoactive drug, 4, 5', 8-trimethylpsoralen (TMeP). This drug is widely used in the treatment of vitiligo and psoriasis. DMeCP is fluorescent, and nonphotosensitizing when tested on guinea pig skin. DMeCP also occurs in the urine of human patients receiving TMeP orally.


H-Y male antigen: detection on eight-cell mouse embryos.

The H-Y (male) antigen is expressed on 50 percent of eight-cell embryos (2 days old) of the mouse, strain C57BL/6. This work provides additional evidence that H-Y expression is not dependent on male differentiation.


Coronary arterial smooth muscle contraction by a substance released from platelets: evidence that it is thromboxane A2.

When human platelets are aggregated by thrombin, material is released that rapidly contracts strips of spirally cut porcine coronary artery. Prevention of the contraction by indomethacin suggested mediation by a prostaglandin. The contraction produced by aggregating platelets was unlike those produced by prostaglandins E2, F2alpha, G2, or H2, but resembled that evoked by thromboxane A2, which is formed by platelets during aggregation.


Microbial degradation of condensed tannins.

A strain of Penicillium adametzi Zaleski was isolated from enrichment cultures with condensed tannins as the carbon source. Low-molecular-weight condensed tannins, extracted and purified from Pinus radiata bark, were used as substrates for quantitative growth measurements on this fungus in defined culture conditions.


Behavioral fever in newborn rabbits.

Rabbit pups, 12 to 72 hours old, did not develop a fever when injected intraperitoneally with a pyrogen and maintained at an ambient temperature of 32 degrees C for 2 hours. When placed in a thermally graded alleyway, animals injected with pyrogen selected gradient positions that represented significantly higher temperatures than controls injected with saline (40.4 degrees in contrast to 36.4 degrees C). Allowing the pups to remain at their selected positions for 5 minutes caused a significant increase in the rectal temperatures of the pyrogen-injected pups but not that of the controls. Thus, newborn rabbits will develop a fever by behavioral means after a single injection of an exogenous pyrogen.


Hardy-Weinberg law: asymptotic approach to a generalized form.

The equilibrium frequencies of a generalized Hardy-Weinberg law are approached at a geometric rate under assortative mating, irrespective of the initial genotypic frequencies. The asymptotic form is similar to that of Wright, and the pattern of assortative mating is based on deviations from the mean genotypic value.


The effect of stimulus sequence on the waveform of the cortical event-related potential.

The waveform of the cortical event-related potential is extremely sensitive to variations in the sequence of stimuli preceding the eliciting event. The waveform changes were manifested primarily in the amplitudes of the negative component of the potential that peaked at 200 milliseconds, the positive component that peaked at 300 milliseconds, and the slow-wave components. A quantitative model was developed relating the waveform changes to changes in event expectancy. Expectancy is assumed to depend on a decaying memory for events within the prior sequence, the specific structure of the sequence, and the global probability of event occurrence. For stimuli relevant to the task, the less expected the stimulus the larger the amplitudes of late components of the event-related potentials.


Successful immunization against the sexual stages of Plasmodium gallinaceum.

Gametocyte infectivity and oocyst development of the avian malaria parasite, Plasmodium gallinaceum, can be reduced or eliminated in mosquitoes by immunizing the chickens on which the mosquitoes feed with infected red blood cells that have been treated with formalin or x-rays. Protection of the mosquito appears to be related to the immobilization of the microgametes in its gut and is associated with the immunoglobulin G fraction of serum.


Myosin synthesis increased by electrical stimulation of skeletal muscle cell cultures.

When cultures of skeletal muscle cells of the chick embryo are subjected to repetitive, electrical stimulation, the contractions increase the amount of protein produced by these cells. The increase is greater for contractile proteins such as myosin heavy chain than for total cellular protein. This demonstrates that in a culture system of skeletal muscle cells that have differentiated in the absence of innervation, one can elicit the protein synthetic response associated with skeletal muscle hypertrophy in vivo.


Biological impact of small air ions.

The thrust of the experimental data presented here is that small air ions are biologically active. There is convincing evidence that both negative and positive ions (i) inhibit growth of bacteria and fungi on solid media; (ii) exert a lethal effect on vegetative forms of bacteria suspended in water when opportunity is provided for contact of cells and ions; and (iii) reduce the viable count of bacterial aerosols. Through physical action, ions of either charge upset the stability of aerolosized bacterial suspensions and, in addition, have a direct lethal effect which is more prominent with negative ions than with positive ions. With regard to the serotonin hypothesis of air ions action, the situation is more complex. The essential fact is that mice and rats display a charge-related metabolic response to air ions and this phenomenon also occurs in humans. Because serotonin is such a potent hormone, the ultimate functional changes incident to air ion action are impressive and account for the signs of symptoms of the sharav syndrome. Alterations in the cumulative mortality rate with three experimental respiratory disease in the mouse also are charge-dependent, positive ions routinely exercising a detrimental effect. Further, in the case of mice infected with influenza virus, ion-deprivation increases the cumulative mortality rate. Since ion depletion is a constant concomitant of modern urban life, one reasonably may speculate about comparable inimical effects on humans.


Flow-field-flow fractionation: a versatile new separation method.

Flow-field-fractionation is a new separation technique that seems likely to have broad applicability. Its theoretical scope includes any solute for which one can find a solvent and a semipermeable membrane. The principles on which the technique is based are presented. Some experiments with polystyrene beads, viruses, and proteins verify that retention depends solely on diffusion coefficients.


Identification of specific changes in the pattern of brain protein synthesis after training.

Double labeling studies with [3H]valine and [14C]valine were used to investigate the pattern of protein synthesis in the brains of goldfish. The protein fractions in three bands (alpha, beta, and gamma) on sodium dodecyl sulfate-polyacrylamide gels indicate that more valine was incorporated in the brains of goldfish that had been trained in a vestibular conditioning task than in the brains of untrained fish or fish trained in a variety of control behavioral situation. Changes in the pattern of labeling were localized in the cytoplasmic fraction of the brain; no increases in labeling occurred in either the nuclear or synaptosomal components. The results suggest that a specific change occurs in the pattern of protein synthesis in the brain after the acquistion of a new behavior.


Abnormal visual resolution in the Siamese cat.

When tested behaviorally, Siamese cats display marked differences in contrast sensitivity compared to ordinary cats. Overall sensitivity is depressed, the high-frequency cutoff point is lower, and there is less falloff in sensitivity at low spatial frequencies. Optical factors may contribute to these differences, or they may be attributable to the well-established anatomical abnormalities within the visual system of the Siamese cat.


The clonal evolution of tumor cell populations.

It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.


Man-made radionuclides and sedimentation in the Hudson River estuary.

Recently deposited fine-grained sediments in the Hudson River estuary contain radionuclides from global fallout produced by atmospheric bomb tests as well as from low-level releases of a local nuclear reactor. Accumulation rates of these nuclides are dependent on rates of sediment deposition and vary with location in the estuary by more than two orders of magnitude. Within the Hudson estuary, New York harbor is currently the zone of most rapid deposition of sediments containing radionuclides, some of which were released from a nuclear reactor about 60 kilometers upstream of the harbor.


Bat mortality: pesticide poisoning and migratory stress.

Organochlorine residues in the fat of young Mexican free-tailed bats, Tadarida brasiliensis, reached the brain and caused symptoms of poisoning after the fat mobilization that takes place during migratory flight was simulated. These chemical body burdens were obtained naturally under free-living conditions at the maternity roost. The data obtained support the hypothesis that pesticides have contributed to recent declines in populations of this bat.


Formation and transport of secondary air pollutants: ozone and aerosols in the St. Louis urban plume.

Emissions from metropolitan St. Louis caused reduced visibilities and concentrations of ozone in excess of the federal ambient standard (0.08 part per million) 160 kilometers or more downwind of the city on 18 July 1975. Atmospheric production of ozone and visibility-reducing aerosols continues long after their primary precursors have been diluted to low concentrations.


Structural basis for ON-and OFF-center responses in retinal ganglion cells.

The inner plexiform layer of the mammalian retina has a bisublaminar organization determined by restricted branching of the terminals of cone bipolar cells and dendrites of class I (large) and class II (small) ganglion cells. Comparison of dendritic field diameters and receptive fiedl center sizes of large ganglion cells suggests that neural circuitry in sublamina a conveys "OFF"-center properties and connections in sublamina b "ON"-center properties to retinal ganglion cells.


Hyaluronidase-induced reductions in myocardial infarct size.

The size of myocardial infarctions following coronary artery occlusion in the rat was determined directly by measurement of creatine phosphokinase activity in homogenized whole left ventricles and by planimetric measurement of the area of the infarctions in histologic sections of serial slices of the left ventricles. Hyaluronidase was shown to produce significant reductions in expected infarct size both 48 hours and 3 weeks after occlusion without impairing fibrosis during the healing phase. Thus, the amount of myocardial necrosis that follows a coronary artery occlusion has been shown directly to be amenable to reduction with a pharmacological intervention.


Nuclear inclusions in Paget's disease of bone.

The ultrastructure of bone cells was examined in biopsies from 18 patients with Paget's disease of bone and from 60 patients with a variety of other bone diseases. A characteristic nuclear inclusion was found in the osteoclasts of each patient with Paget's disease. The nuclear inclusion most closely resembles viral nucleocapsids of the measles type.


Depletion of brain catecholamines: failure of ocular dominance shift after monocular occlusion in kittens.

Monocularly deprived kittens were compared with littermates that had had their eyelids sutured for the same time but that had, in addition, been treated with 6-hydroxydopamine to deplete their forebrains of catecholamines. The visual cortices of all the catecholamine-depleted kittens showed high proportions of binocular neurons, in contrast to the control group, most of whose visual cortical neurons were driven exclusively by the nondeprived eye. Catecholamines may play an important role in the maintenance of cortical plasticity during the critical period.


Responses of infants to visually presented objects.

The reaching behavior of some 60 infants between 7 and 23 days of age was studied. Contrary to some other reports, the infants did not respond differently to a visually presented, graspable, solid object than to its two-dimensional representation.


Sexual dimorphism in vocal control areas of the songbird brain.

In canaries and zebra finches, three vocal control areas in the brain are strikingly larger in males than in females. A fourth, area X of the lobus parolfactorius, is well developed in males of both species, less well developed in femal canaries, and absent or not recognizable in femal zebra finches. These size differences correlate well with differences in singing behavior. Males of both species learn song by reference to auditory information, and females do not normally sing. Exogenous testosterone induces singing in female canaries but not in female zebra finches. This is believed to be the first report of such gross sexual dimorphism in a vertebrate brain.


[Potassium and sodium electrolyte ratio in the myocardium following death by hanging and electric current].

The amount of the electrolytes of potassium and sodium contained in different parts of both the chambers and the septa between them was investigated flame photometrically in practically sound persons who died on account of a mechanical asphyxiation by hanging--25 cases--and of an electric accident--12 cases. Statistically significant changes in the eletrolytes of potassium and sodium were detected in cardiac muscle in cases of an electrotrauma as against hanging. In connexion with the changes in the above electrolytes the fragmentation of the muscle fibers of the heart was enquired into. No strict correlational dependency between the changes of electrolyte balance and the degree of fragmentation was found.


Overcoming inertia in the planning of a burn care facility.

Various problems, involving money, space, personnel, and their relationship to the hospital administration, can be associated with the establishment of a Burn Unit. However, these problems can be overcome. During the creation of a Burn Unit, consultation regarding the design features of the unit is particularly important.


Problems in management of the pregnant patient with rheumatic heart disease and valve prosthesis.

The clinical course, through pregnancy and delivery, of a 30-year-old woman with rheumatic heart disease and a prosthetic mitral valve is presented. Despite maternal development of congestive cardiac failure and atrial fibrillation, the delivery of a healthy infant was achieved. The problems encountered during pregnancy and delivery in patients with rheumatic heart disease and prosthetic valves are discussed. These include the management of long-term anticoagulant therapy, prophylaxis against rheumatic fever and subacute bacterial endocarditis, impaired cardiac function, atrial fibrillation, breast feeding, and contraception as they relate both to the mother and the fetus and infant.


Case finding of unrelated disease in the orthopedic clinic.

Protocols for detecting hypertension and pelvic disease were established in the orthopedic outpatient department. A significant percentage (hypertension, 20%; pelvic disease, 10%) of the patients were found to have undiagnosed pathologic conditions. The cost to the orthopedist of such case finding was minimal in terms of time and money. Methods of securing adequate follow-up are discussed.


Avascular necrosis of the body of the talus after combined medial and lateral release of congenital clubfoot.

A retrospective study was made of 203 patients with 321 congenital clubfoot deformities who had at least one operative procedure at the Shriner's Hospital in Greenville, South Carolina, in a period from 1944 to 1973. The five cases of avascular necrosis of the talus occurred among the 35 patients having combined medial and lateral releases. These five clubfeet were recurrent and recalcitrant and required extensive soft tissue release to achieve sustained correction. It is recommended that dissection of the subtalar joint, except at the talonavicular joint, be avoided and that extensive lateral ankle dissection, especially when the sinus tarsi is included, should not be performed simultaneously with the medial release unless absolutely necessary to achieve the desired anatomic relationship.


Depression among the aged.

Depression in the elderly is a public health problem that will increase in magnitude as a progressively larger proportion of our population consists of those over the age of 65. Epidemiologic studies indicate that the elderly are in need of physical and mental health care. New data from 1,645 respondents in a Southeastern county show the high frequency of depressive symptomatology in the elderly and a significant relationship between poverty and depressive symptomatology. Predominant symptoms were lowered spirits, feeling helpless, a gloomy outlook on the future, a sense of powerlessness, and difficulties with sleep and appetite. A social psychiatric orientation is needed to supplement the more traditional psychodynamic formulations of depression in the aged. Adverse social conditions and cultural biases deprive the elderly person of a requisite level of self-esteem and place him at risk for depression. Treatment included humanistically based psychotherapy which can be carried out by doctors, the use of antidepressants, medications, and the development of social support systems.


Rubella: pattern of outbreak in a university.

During the spring term of 1975, rubella was diagnosed in 23 students at Georgetown University in Washington, DC. The cases were concentrated among students from the School of Foreign Service and their close contacts; outbreaks did not appear in other divisions of the university. Rubella immunization of susceptible female college personnel is recommended.


Abdominal thermography in infantile and childhood liver disease.

Thermography provides an indication of the infrared energy emitted from various skin surfaces and, usually, reflects heat conveyed there from underlying organs. We have used abdominal thermography to study 62 infants and children with acute and chronic liver disease. Thirty-four healthy infants and children were studied as controls. Thermograms were abnormal in 96% of all patients with liver disease. The most common pattern was diffuse heat emission over the liver area, either alone or in combination with vascular and/or mottled patterns. A mottled pattern was more common in chronic liver disease. Although follow-up thermograms were obtained in 28 patients, the data obtained for different types of liver disease are as yet insufficient to warrant conclusions. However, it appeared that reversal of an abnormal thermogram to normal was associated with improvement of liver function and histologic findings in two patients with acute viral hepatitis. On the other hand, persistence of abnormal thermographic records was always associated with persistent hepatic disease as determined by histology and tests of liver function.


Clinical trials of tonsillectomy and adenoidectomy: limitations of existing studies and a current effort to evaluate efficacy.

Indications for tonsillectomy and adenoidectomy (T&A) are both uncertain and controversial. Only five prospective clinical trials of T&A have been reported. These studies provided important data, but failed to test the efficacy of the procedures in children most affected by tonsil- and adenoid-related conditions. A study currently under way focuses on just such children and also explores related immunologic issues.


Ostium primum atrial septal defect in the adult.

Seven adults with ostium primum atrial septal defect (ASD) are presented. All but one patient were symptomatic at the time of diagnosis with the average age being 41 years. At catheterization each had a large, low ASD, left-to-right shunt, and a cleft mitral valve leaflet with minimal regurgitation. Pulmonary hypertension occurred in one. Six patients are asymptomatic an average of 3.5 years after surgical correction. One patient died of other causes at 18 months. Rapid decompensation secondary to arrhythmias or atrioventricular block occurs much more frequently with primum than with secundum ASDs, approaching 80% by age 45. Follow-up in this series suggests that surgical correction may prevent these developments.


Tuberculous meningitis in children before and since isoniazid.

The use of isoniazid (INH) in persons exposed to active cases of tuberculosis has been challenged, Reports of toxic reactions to isoniazid warrant a review of the drug's potential benefits and hazards. This prompted a retrospective survey of cases admitted to a large county hospital to determine admission incidence before and since initiation of a program of case-finding and INH chemoprophylaxis for children in 1953. During the 24-year period surveyed (1950-1973), the population of the county increased twofold while the yearly admission rate for tuberculous meningitis in children fell from a high of eight cases to a low of two. This dramatic drop in cases admitted, coupled with an absence of any toxic reactions to the drug, provides support for continuation of the program of case-finding and isoniazid chemoprophylaxis.


Perforating ocular shotgun injuries: relationship of ocular findings to pellet ballistics.

A retrospective study of 20 cases of perforating ocular injuries due to shotgun pellets revealed visual acuity of hand motions or worse in 85%. Massive persistent vitreous hemorrhage was present in 75%. Double perforation of the globe was present in 60% of the involved eyes. Product safety measures are recommended.


Current management of digitalis intoxication.

Of the commonly used drugs, digitalis has one of the highest therapeutic-toxic ratios. Mortality is significantly increased in the 20% to 30% of patients on digitalis who are in a toxic state when admitted to the hospital. Successful use of digitalis depends on avoidance of its use in situations likely to result in toxicity; recognition of the signs, symptoms, and electrocardiographic findings of digitalis intoxication; and stopping digitalis completely as the initial treatment of digitalis intoxication.


The diagnosis and treatment of leprosy.

Leprosy is a complex disease, but recent research and the Ridley-Jopling classification which emphasize its immunologic aspects have greatly aided our understanding of and approach to the problem. The diagnosis should be considered whenever skin lesions and sensory loss occur. Dapsone remains the treatment of choice, but several newer drugs show great promise, especially in those cases whose bacilli have become sulfone resistant. Immunotherapy may play an increasingly prominent role in the future. Reactive episodes continue to be a serious complication, but the availability of thalidomide to control erythema nodosum leprosum has markedly improved the prognosis. Physicians of the US Public Health Service Hospital at Carville, Louisiana, are available at all times for consultation on these and other matters related to leprosy.


A direct procedure for the micro-scale preparation of acyl derivatives of nucleophilic drugs from carboxylic acids for gc separation and identification.

Free carboxylic acids were converted into mixed anhydrides suitable for the acylation of nucleophilic drugs in a one-step procedure. By preparing more than one acyl derivative and comparing the retention times of the derivatives with those of authentic drug samples with reference to suitable internal standards, the positive identification of unknown drugs was possible. The method is suitable for use in conjunction with the microphase extraction of drugs.


A scanning electron microscope study of the developing rat secondary palate.

The surfaces of the developing secondary palatal shelves and palate, in Wistar strain albino rats, were examined using scanning electron microscopy. Beginning on the 16th day after insemination there was a progressive degeneration of the cell surfaces on the medial aspect of the shelves. This took the form of a loss of surface microvilli and intercellular boundaries accompanied by the appearance of clefts between the cells. Fusion of the palate was complete by the 18th day and two epithelial zones could be recognized in the soft palate. The cell surface degeneration is possibly an essential change prior to shelf fusion.


Efficacy of cryotherapy in retinoblastoma.

Five cases of retinoblastoma treated be freezing are reported. From these cases it appears that a single freeze-thaw cycle will destroy all tumour and that with suitable instruments it is possible to destroy tumours involving up to 30% of the volume of the globe without causing blindness.


Physicians and sex therapy.

The physician's role in sex therapy is discussed. Problems of sexual dysfunction and guidelines for physicians who wish to engage in sex therapy are set out briefly.


Herb use and necrodegenerative hepatitis.

Twelve patients with herbally-induced hepatitis are described and the clinicopathological features of their illness, which seem to present a recognisable spectrum, are discussed. The nature and the severity of the histological changes seem to correlate with the clinical manifestations and the immediate prognosis. Laboratory tests, especially liver function studies, are of limited diagnostic and prognostic value. The plants which contain the responsible toxins, have been identified in this country and in other parts of Southern Africa. A short list is provided of, apparently, the commonest medicinal plants in Lesotho. Many more toxic plants, however, are used in food and in diverse traditional medications. Senecio species are the principal source of hepatotoxic alkoloids, especially pyrrolizidines. Experimental studies ann evidence of similar disorders in animals, have thrown some light on the pathogenic mechanisms of these hepatotoxic and possibly hepatocarcinogenic agents. The disease in humans probably results from a combination of factors.


Safety restraints for children travelling in motor vehicles.

The parents of 202 children were questioned about their use of safety restraints for their children while they were passengers in a motor vehicle. The result of the survey shows a low incidence of use of safety restraints by both parents and their children and that the type used for children was, in the majority of cases, both inadequate and dangerous. There was a correlation between the use of safety restraints by both parent and child on the day of questioning, but no association was found between the use of these restraints and the social class, educational standard achieved, income group, home language or home province of the parents. Neither was there any association between the use of safety restraints and a history of previous traffic accidents which had involved the family or close friends. In South Africa, the number of deaths in childhood as a result of motor vehicle accidents exceed those from the same cause in the United Kingdom. We consider that the medical profession in this country should inform the public of the desirability of fitting and using safety restraints of the correct type for children while they are passengers in motor vehicles. Reasons for the high incidence of serious injuries to children who are passengers in motor vehicles are reviewed and the methods of restraining children of different ages are discussed.


Computerised axial tomography.

Computerised axial tomography has made an impressive impact on surgical neurology, and when the body scanner becomes available it will no doubt have similar advantages for the other specialities. It is a safe non-invasive method of investigating pathological processes of the brain. The amount of information so obtained is accurate to within 1% and at least a hundred times more inforation is obtained than from ordinary X-ray investigations. A review of 1 000 patients scanned is presented. Computerised axial tomography, if artefacts are eliminated completely, is most unlikely to yield a false positive scan. Its greatest value, however, is in the diagnosis of lesions in patients with head injuries and abscesses because these patients are very often moribund, and angiography, even when done expertly, may aggravate the clinical condition. Orbital and retro-orbital tumours have proved to be difficult to display other than by the EMI scanner methods. Acoustic neurinomata and meningiomata are also displayed with clarity, but owing to 'overshoot' artefact, other lesions, which do not enhance to the same extent on injection of Conray or Urografin, still offer a diagnostic problem. The investigation of epileptic patients has proved disappointing for the same reason that artefact obscures the low temporal lobe cut.


Ageing in a plural society.

The differential position and involvement of the aged in each population group in the Republic of South Africa are illustrated on the basis of an analysis of the age structure of the population, sex ratios, life expectancy, degree and nature of urbanisation and industrialisation and family structure. It is concluded that the problems and needs of the aged in modernising plural societies differ for each population group, and that there thus exists a need for a flexible and non-dogmatic approach to the needs of the aged.


Genetic disorders in Southern Africa.

Certain uncommon genetic disorders occur relatively frequently in the various population groups of Southern Africa. Prominent among these are porphyria, colonic polyposis and sclerosteosis in the Afrikaner community, Huntington's chorea in the British, Gaucher's and Tay-Sachs diseases in the Jewish population, glucose-6-phosphate dehydrogenase deficiency (G-6-PD deficiency) and thalassaemia in the Greek community, various skeletal dysplasias in the Black group, lipoid proteinosis and cleidocranial dysostosis in the Cape Coloured population, diabetes mellitus in the Indian community and retinitis pigmentosa in the Tristan da Cunha islanders. In addition, 'private' syndromes have been encountered in virtually every group. Awareness of the ethnic distribution of unusual genetic conditions is of considerable practical importance during the differential diagnosis of obscure disease.


Isoniazid acetylator status of Black South African tuberculosis patients.

Black male tuberculosis patients (106) were phenotyped into 59% fast and 41% slow acetylators with isoniazid (NH) plasma half-lives. The antimode time dividing the two acetylator groups was longer than that previously reported for Whites. The therapeutic significance of INH acetylator phenotyping per se is questioned since it provides neither a measurement of the amount of INH absorption nor of its distribution within the body.


Haemodynamics and treatment of right ventricular infarction.

In this article 2 cases of myocardial infarction with haemodynamically dominant right ventricular infarction are reported. The incidence and significance of the condition are discussed. The use of haemodynamic monitoring in diagnosis and management is stressed and the response to fluid therapy, either alone or together with inotropic drugs, is discussed.


Poisoning associated with witchdoctor attendance.

Eight patients with poisoning associated with treatment by a witchdoctor are presented. Six patients died. A therapeutic approach to the problem is suggested.


The effect of diazepam on human pancreatic secretion.

The effect of intravenous and intramuscular administration of diazepam on secretin- and cholecystokinin-stimulated pancreatic secretion was studied in man. Diazepam was not found to have a significant effect on mean volume out-put, bicarbonate and enzyme concentrations and colour index. It was acceptable as premedication for routine pancreatic function studies.


Measuring emotional stress in Africa: the difficulties involved and some results.

Two surveys of emotional stress were undertaken and the difficulties experienced in each survey are discussed. In the first survey, 3 sets of personality inventories, selected to identify the type A personality that is associated with the early onset of coronary heart disease, were completed by 95 men, aged from 40 to 50 years, who came from 4 groups: White Rhodesians, urban Blacks of high and low social status, and Blacks from a rural area. The same trend was shown by all 3 inventories, which indicates that type A behaviour is least common among Whites, becomes progressively more marked in Blacks of upper social class, then in Blacks of lower social status, and is greatest in Blacks living in a rural environment. The psychogalvanic response to emotional stress (fear) was used to assess autonomic lability in the first 3 groups.


Coagulation and fibrinolytic properties of peripheral venous blood in chronic ectopic pregnancy.

The coagulation and fibrinolytic properties of peripheral venous blood was studied in 10 Black patients with chronic ectopic pregnancy. There were significant elevations of plasma fibrinogen and serum fibrin-fibrinogen degradation products (FDP) and prolongation of the euglobulin lysis time. These features are believed to be compatible with chronic inflammation. No evidence of a haemostatic defect was found.


Geriatric care: where does the responsibility lie?

In contrast to purposeful efforts in South Africa to lay sound foundations for the development of social services for the aged, little constructive planning has been done by medical authorities to provide for the special health needs of the elderly on a national basis and based on recognised geriatric principles.


Hypertension detected in young black women by routine screening in a family planning clinics.

The prevalence of hypertension, defined as a diastolic blood pressure over 100 mmHg, among young Black women who attended a family planning clinic in Johannesburg, was 2,85%, while in those over 35 years of age it was 8,5%. There was no correlation between hypertension and urbanisation, occupation or urinary sodium output. Within 6 months of diagnoisis, 84% of the women with hypertension had defaulted from the treatment clinic. Family planning clinics can economically screen patients for hypertension, but in this community a separate screening programme would not succeed until patient compliance has improved.


[Cycling, fitness and the prevention of ischemic heart disease].

A short review of the prevalence of ischaemic heart disease in South African Whites is given, and primary prevention, which entails an alteration in life style, is emphasised. The role of increased physical activity in primary prevention is discussed. Any programme to increase the fitness status of a population based on activities that must be performed outside the daily routine, willhave limited impact. The possible role of cycling is discussed and it is shown that ordinary cycling to work probably causes sufficient stimulation of the cardiovascular system to produce an acceptable standard of physical fitness.


Pulsus paradoxus in the bedside assessment of patients with bronchial asthma.

Pulsus paradoxus (PP) was measured in 35 patients with bronchial asthma. The presence and degree of PP correlated well with the clinical conditions of the patient and with peak expiratory flow rate (PEF). PP and PEF are useful bedside measurements in the assessment and management of patients with bronchial asthma. Although the degree of PP is usually directly related to the severity of the attack of asthma, it was absent in the one patient who remained severly ill with unreleived bronchospam when he became exhausted. Our experience with this patient, and with previous patients who are not included in the present analysis, emphasises the fact that PP must not be considered in isolation but in conjunction with the patient's clinical state and with other indices of the severity of the astmatic attack.


An interracial comparison of insulin secretion in normal non-pregnant women.

The plasma insulin response to oral glucose in normal, non-pregnant, premenopausal Indian, Black, andWhite women was investigated. Indian women responded by an excessive secretion of insulin relative to the other two groups. This primarily affected the late phase of insulin release.


Geriatric medicine - the challenge of the 1970s.

The rising number of elderly people in the community poses a great challenge to the medical and allied professions. This article outlines the urgent need for the planning and provision of comprehensive services for the elderly. The importance of health surveillance, a preventive approach and the health team work is stressed. The need for the introduction of geriatrics into undergraduate and postgraduate medical education is emphasised.


Subcutaneous phycomycosis from Pondicherry, South India.

Four cases of subcutaneous phycomycosis diagnosed by isolating Basidiobolus meristosorus from affected tissue, are reported along with the growth characters and morphological features of this fungus. This is the first report from Pondicherry, South India where it was it was possible to isolate the causative fungus from each case.


Sulphitolysis in keratinolysi. Biochemical proof.

The presence of S-sulphocysteine in filtrates of the dermatophyte Keratinomyces ajelloi growing on human hair in a culture medium buffered by pH 7-4 by phosphates was demonstrated by means of ion exchange chromatography techniques. S-sulphocysteine being destroyed during acidic hydrolysis was identified after enzymic hyrolysis of dialyzed and lyophilized filtrates. This result indicates that sulphitolysis occurs during kerationlysis performed by K. ajelloi. As thiosulphuric esters were shown present in hair perforations made by Microsporum gypseum, we think sulphitolysis is a common mechanism developed by dermatophytes to attack keratin.


A cytological study of morphogenesis in Coccidioides immitis.

Coccidioides immitis is still classified as a Deuteromycete because the perfect stage is unknown. Mating experiments have been unsuccessful. Some investigators consider the endosporulating spherule to be a sporangium with sporangiospores, but others describe it as an ascus. The development of a reproducible method for cultivation of the spherule-endospore cycle in vitro provided an opportunity to study cytological changes occuring throughout the arthrospore-hyphae-arthrospore cycle and the arthrospore-spherule-endospore cycle. Our observations of the arthrospore-mycelial cycle confirm an earlier report by another investigator demonstrating a resting stage followed by ring formation, a V-form, and a filament stage. In addition, we describe four pairs of chromosomes and formation of possible spindles and nucleoli. The spherule-endospore cycle is initiated by an arthrospore with a single large nucleus, most probably derived from the multinucleate arthrospores in the inoculum. This uninucleate arthrospore is present for less than 24 hours. During continued incubation, the arthrospore becomes a round cell with four pairs of chromosomes. Subsquently, the cell enlarges to become a spherule and this growth is accompanied by a series of synchronous divisions of the nuclei. Although endospores are formed apparently progressive cleavage, clusters of uninucleate endospores are enclosed in a membranous sac as seen in squashed spherule preparations. The question of a relationship to the phycomycetes or the ascomycetes remains unresolved.


Preliminary studies on conidial liberation of Blastomyces dermatitidis and Histoplasma capsulatum.

Controlled attempts to release viable conidia from cultures of Blastomyces dermatitidis and Histoplasma capsulatum with air samplers were unsuccessful. Air velocity was not fount to be a limiting factor since the conidia remained attached after conidiophores had been violently shaken by air currents in an observation chamber. Wetting these same conidiophores readily released the conidia. It is inferred that in nature conidia may be liberated by exposure to water and then dispersed by air currents.


A study on transformation in a mutant of Candida pseudotropicalis.

This paper reports on the possible influence of various factors on the frequency of transformation in Candida pseudtropicalis. The concentration of DNA used varied between 25 mug and 100 mug/ml. The maximum percentage transformation 0-16% occured at 75 mug/ml.


Isolation of Sporothrix schenckii in the soil in Israel in relation to a new case in man.

A new case, the third in Israel, of subcutaneous sporotrichosis is presented. A pigmentary strain of Sporothrix schenckii was cultured from the unopened and necrotic nodules of the left hand and forearm of an 80-year-old male. Experimental inoculation of the isolated fungus into mice led to the dissemination of the organism in the liver, kidneys and lungs inoculated intraperitoneally, and the development of orchitis with abscess formation in those inoculated intratesticularly. In both groups of mice the causative agent was successfully recovered. Three months of treatment with oral potassium iodide led to the disappearance of the lesions. The source of contamination was found to be the soil adhering to fragments of wood. Two strains of a fungus, morphologically identical to the human S. schenckii, were isolated through the mouse procedure and agar-plating method from soil samples collected in the vicinity of the patient's residence. The soil isolates also proved to be pathogenic in animal inoculation. This is the first isolation of S. schenckii from soils in Israel. The possible relationships between the soil isolates and Ceratocystis stenoceras are discussed.


La maladie post-operatoire: Is there order in variety? The six stimulus-response sequences.

The search for a unifying concept in all post-traumatic metabolism, symbolized by the phrase "la maladie post-operatoire" has been a fruitful one, not so much because of success, as through its very failure. There is such variety in convalescent patterns that it has made it essential for students of this subject to look more closely at the nature of the stimulus response patterns and bring sharply into focus those recurring phenomena whose mixture together determines the final clinical result. In this brief introductory paper six groups of stimulus-response patterns have been identified and analyzed. The clinician needs an understanding of these patterns in everything that he does for the patient, both within the operating room and on the ward. The student of surgery must make an effort to differentiate amongst the six stimulus-response patterns. If he fails to do so he will be analyzing all surgical recovery as falling under a single sequence, an error that has been all too frequent in the literature. There may be other stimulus response patterns of greater importance which will be added to the list presented here, as research in the coming decades increases our understanding of convalescent biology. This presentation will serve as an introduction to the other papers gathered in this symposium by Dr. Clowes, all of which cast further important light on the details of the stimulus and response in surgical metabolism.


Thrombosis and intravascular coagulation.

Stress, including trauma and sepsis, is associated with a state of hypercoagulability. In these circumstances the patient is at risk of generalized or local thrombotic complications. New laboratory investigative procedures facilitate diagnosis and permit improved assessment of therapy, which at present remains of unproven efficacy both in the general and local situation.


Anaerobic mediastinitis.

Three patients with anaerobic mediastinitis associated with retropharyngeal abscess have been encountered recently. Dental infections accounted for two instances, and the third instance resulted from rupture of the thoracic esophagus from blunt trauma. Each was marked by extreme difficulty in achieving complete abscess drainage due to the initially unrecognized virulence of the causative anaerobic bacteria. Complications were frequent and included empyema, pericarditis and aspiration pneumonia. The combination of vigorous diagnostic efforts, prompt operation and reoperation when necessary plus specific antibiotic effective against anaerobes led to a successful outcome for each patient.


Radioactive technetium phosphate bone scanning in preoperative assessment and follow-up study of patients with primary cancer of the breast.

Seventy-five female patients with early primary cancer of the breast were studied by bone scanning with 99mTc labeled phosphate at the time of initial presentation and serially during follow-up examination. Eleven patients had an abnormal bone scan at the time of presentation. During follow-up periods, which have ranged from three to 34 months with a mean of 16 months, abnormal bone scans have developed in a further 13 patients. To date, nine of the 24 patients with an abnormal bone scan have died, while only one of the 51 with a persistently normal scan has died. It is concluded that an abnormal bone scan carries a significant risk of earlier death due to metastatic disease.


Needle biopsy of the thyroid.

As with any specialized diagnostic technique, the degree of success and safety of needle biopsy of the thyroid are largely based on experience. While an adequate core of tissue for examination is imperative, the interpretation by the pathologist is equally important. A close liaison of the latter with his clinical colleagues is necessary for optimal pathologic evaluation. A review of this experience during a 20 year period shows that needle biopsy is a reliable diagnostic procedure in more than 90 per cent of the patients. It is unlikely to disseminate the disease or compromise the prognosis, and it is a safe office procedure.


Intravenous iron-dextran therapy in the treatment of anemia occurring in surgical, gynecologic and obstetric patients.

An infusion of iron-dextran diluted in 1,000 milliliters of physiologic saline solution was given to 51 patients. The average hemoglobin response was 1.9 grams per deciliter per week. Mean corpuscular volume, mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin deficits also were corrected. There were no allergic reactions. This is an extremely reliable and safe method of replenishing depleted iron in patients.


Risk factors in pulmonary embolism.

The influence of several diseases and conditions upon the prevalence of pulmonary embolism in autopsies performed during a ten year period at the University of Michigan has been analyzed. The major factors contributing to an increase in risk of development of pulmonary embolism include heart disease, certain types of cancer, obesity, acute paraplegia and accidental and operative trauma. These and several other risk factors defined in other studies should be used in a selective program designed to increase the rate of detection of deep venous thrombosis before pulmonary embolism occurs, or alternatively, patients at increased risk should receive prophylactic low dosage heparin therapy during hospitalization.


Acute renal failure after ligation of the hepatic artery.

Acute renal failure developed in nine of 78 patients who were subjected to hepatic artery ligation for nonresectable and extensive malignant tumor of the liver. Of those nine, six had hepatomas, one cholangiocarcinoma, one metastatic islet-cell carcinoma and one metastatic melanoma. Preoperative renal function as reflected in blood-urea-nitrogen and serum creatinine values was within normal limits. There were marked elevations of serum glutamic-oxalacetic transaminase and lactic dehydrogenase levels after hepatic artery ligation, an indication of massive ischemic injury of the tumor and the liver. A diagnosis of acute renal failure was established within 14 to 70 hours after hepatic artery ligation. In five patients, oliguric renal failure developed, and in four, high urinary output renal failure. In only three patients did systemic hypotension and hypovolemia precede acute renal failure. Seven of the nine patients died. Postmortem examination was done in five patients, and in only two was there evidence of renal tubular necrosis. The factors contributing to acute renal failure appear to be extensive involvement of the liver by tumor, presence of ascites and jaundice, occlusion of the portal vein and hyperuricemia. The presence of any one of the foregoing contraindicates the procedure.


Evaluation of dissection of the axilla in modified radical mastectomy.

Fifty consecutive unselected patients with infiltrating carcinoma of the breast underwent radical mastectomy in two consecutive stages. The initial operation was a modified radical mastectomy, with preservation of the pectoral muscles, and the second stage, a procedure to transform the initial operation into a standard radical mastectomy. An analysis of the location and the number of the lymph nodes recovered in the two stage operation shows that a so-called modified radical mastectomy is inadequate to ensure the clearing of the axilla. Lymph nodes were recovered at the second stage of the operation in 36 patients, and seven of these patients had metastasis. Modified radical mastectomy was effective in erradicating the lymph nodes of the lower part of the axilla but inadequate for lymph nodes at levels II and III and, especially, the interpectoral lymph nodes.


Evaluation of use of the rigid dressing in amputation of the lower extremity.

Twenty-seven arteriosclerotic amputees were evaluated to determine the value of the rigid dressing technique for amputation wound management. Results were compared with those for patients having conventional stump wound management. The two groups were similar in number, age and incidence of diabetes. All the patients treated with the rigid dressing had primary healing of the amputation wound, while 13 patients treated with the conventional dressing had primary healing. Long term rehabilitation to the use of a prosthesis was not improved by the application of a rigid dressing on the amputation wound. Our current preference is use of the rigid dressing applied in the operating room at the time of amputation. If the wound is satisfactory and the general condition of the patient is such that he can use a temporary pylon, it is attached to the cast at the first change, about two weeks after operation.


Reversal of renal failure and control of hypertension in patients with occlusion of the renal artery.

Results of arteriographic investigation of patients with deteriorating renal function or poorly controlled hypertension have revealed that thrombosis of the renal artery is not an uncommon exacerbating factor. Seventeen patients with one or more occluded renal arteries had an operation to improve renal function or to control hypertension. Stenosis of the contralateral renal artery was present in addition to the occlusion in four patients. Reconstructive arterial procedures were performed in 15 patients and nephrectomy was performed in two. Eight patients with renal failure had marked improvement in renal function after revascularization of the occluded renal arteries. The group had a mean preoperative serum creatinine value of 7.95+/-1.81 (S.E.) milligrams per cent which fell postoperatively to 3.91+/-1.21 (S.E.) milligrams per cent at a mean follow-up period 20 months. Preoperative control of hypertension was difficult in 16 of the 17 patients. Postoperatively, the blood pressure fell to normal levels in six patients, and in an additional eight patients, it did so with the administration of antihypertension therapy. The hypertension was unchanged in two patients. Plasma renin activity was measured in 14 of the patients with hypertension. It was elevated in 13 patients and normal in one patient. Postoperatively, the blood pressure was unchanged in the patient with normal plasma renin activity, but in 12 of the 13 patients with elevated plasma renin activity, the blood pressure returned to normal levels. It is concluded that patients with occluded renal arteries should be treated surgically. The major benefits of an aggressive approach to this condition are reversal of renal failure and control of hypertension.


Accuracy of Doppler ultrasound in clinically suspected venous thrombosis of the calf.

Doppler ultrasonic examinations and contrast phlebography were performed on 55 limbs of 43 patients with a clinical diagnosis of venous thrombosis of the calf and without phlebographic evidence of thrombosis above the knee. There was diagnostic concurrence of Doppler and venographic evaluations in 46 of 55 limbs studied. There was only one instance of a false-negative diagnosis by Doppler examination. Of the eight false-positive Doppler examination findings, an alternate clinical diagnosis affecting venous flow in the calf was evident in six patients. The diagnostic importance of augmentation of flow velocity of the posterior tibial vein upon release of compression of the calf is emphasized. A normal Doppler examination finding may accurately exclude significant deep venous disease in a patient with clinical manifestations of venous thrombosis in the calf.


Beneficial effect of prostaglandin E1 in experimental hemorrhagic shock.

Twelve dogs were subjected to hemorrhagic shock by means of a modified Wiggers technique. Half were treated with prostaglandin E1, 1 microgram per kilogram per minute in 60 milliliters of saline solution, for one hour after shock, while the other half received only an equal amount of saline solution. Those dogs treated with prostaglandin E1 exhibited a significantly increased survival time and cardiac output as well as a significantly lowered total peripheral resistance when compared with those for untreated dogs. The various modes of action by which prostaglandin E1 exerts both its cardiovascular and other long term effects indicate a multisystem effect of the drug.


The mechanism of capillarity in surgical dressings.

By appreciating the concept of capillarity and by determining whether or not the dressing to be used next to the wound should be hydrophilic or hydrophobic, a dressing can be designed that acts to remove secretions from a draining wound. It also may protect a wound from exogenous secretions.


Anatomic localization and step by step advancement of the fiberoptic colonoscope.

Anatomic localization of the tip of a colonoscope without the aid of fluoroscopy is adequate in a majority of patients. External check points of transilluminated light within the colon on the abdominal wall, characteristic internal appearance of the colon and gross anatomic landmarks have been used. An improved technique for advancement results if a routine sequence of maneuvers is used in a similar manner in all patients.


The effects of coronary vasodilatation on cardiac performance during endotoxin shock.

Results of studies have suggested that endotoxin and lowered coronary arterial perfusion pressures are detrimental to cardiac performance and lead to failure. Prevention of cardiac failure in the isolated canine heart preparation confronted with endotoxin and decreased coronary perfusion pressure was possible by perfusing these hearts with sodium nitroprusside. Prevention of failure was manifested by a lowered left ventricular endiastolic pressure and was associated with increased coronary flow and decreased coronary resistance with increased oxygen delivery and decreased oxygen extraction. Possible explanations for improved performance by dilator perfusion include increased delivery of oxygen and nutrients to myocardial tissue as well as a reduction of ventricular wall tension by dilating the coronary vascular skeleton. Prevention of extravasation of interstitial fluid into myocardial tissue by reducing overperfusion of potentially damaged coronary vessels could serve to maintain myocardial integrity and ventricular compliance. The potential use of such therapy warrants further study, with emphasis on evaluating the hemodynamics of the intact animal.


Kinin activation in the blood of patients with sepsis.

To determine whether or not kinin activation in the blood during severe infection with gram-negative bacteria may be related to hemodynamic abnormalities encountered, blood prekallikrein, kallikrein inhibitor and kinin values in 2l surgical patients with sepsis were compared with those in normotensive and hypotensive states. Because of reduced prekallikrein synthesis in patients with hepatic insufficiency, the normotensive and hypotensive groups were each subdivided according to the presence or absence of liver dysfunction, as indicated by elevated blood bilirubin, serum glutamic-oxalacetic transaminase or alkaline phosphatase levels. The mortality was zero in group 1, normotensive normal liver function; 80 per cent in group 2, hypotensive-normal liver function; 20 per cent in group 3, normotensive liver dysfunction, and 67 per cent in group 4, hypotensive liver dysfunction. Ultimately, the majority of deaths were due to respiratory failure. Although the blood prekallikrein level, was below normal in all groups and was significantly less in all patients with liver dysfunction, it was reduced proportionately in hypotensive patients to less than 30 per cent of the values noted in the two normotensive groups. This finding suggests prekallikrein consumption in the hypotensive groups to be the result of the process of activating kallikrein and bradykinin. This concept is supported by finding elevated kinin values, above 3 nanograms per milliliter of plasma, in only 28 per cent of those in group 1 and 12 per cent of those in group 3, while in the hypotensive patients, groups 2 and 4, the kinin level was elevated in 60 and 66 per cent, respectively.


Zinc and wound healing.

A review of the literature on zinc and wound healing shows the many gaps of knowledge which still exist. This study of the histologic appearance of wound healing in rats fed various diets demonstrates the serum zinc levels achieved by such diets. No significant improvement was observed in the rate of healing for any one group, but a number of histologic differences were observed.


Duodenal anomalies and the ampulla of Vater.

The results of the surgical correction of congenital duodenal anomalies in infants free of severe prematurity, mongolism or other intestinal anomalies are most favorable. Several uncommon defects involving the second part of the duodenum, which required special attention to the anatomic proximity of the ampulla of Vater and the terminal portion of the common bile ducts have been encountered. The recognition of this intimate relationship may prevent inadvertent injuries to these structures, further improving the results of operative procedures for these difficult congenital malformations.


Hydatid disease of the liver with thoracic involvement.

Eleven patients with hydatid disease of the liver with intrathoracic involvement have been treated at this hospital, and another patient was treated previously elsewhere. The clinical and roentgenologic symptoms depend greatly upon the evolutionary stage of the disease. General conditions are seriously affected in instances of ruptured and infected cysts. When the cysts open into the tracheobronchial tree as a result of coughing up pus in profuse quantities, the general condition may improve to a certain degree, but bronchopulmonary symptoms increase at that moment. An important spitting of bile must alert us to the existence of biliary hypertension. This condition must be treated first to avoid recurrence of the process. According to our experience, surgical treatment is based upon correct drainage of the cystic intrahepatic cavity under the diaphragm, separating the pleural cavity completely from the intrahepatic; excision of the transdiaphragmatic fistulous tract; conservative indications for pulmonary resection, and possible existence of biliary hypertension before and after operation.


Lactate metabolism in the dog during shock from hemorrhage, cardiac tamponade or endotoxin.

The elevated arterial lactate concentration in shock was investigated by measuring lactate production and clearance rate using a constant infusion of 14C-labeled lactate. In addition, the pathways of lactate metabolism were characterized by determining the percentage of lactate under-going oxidation and the percentage of the total carbon dioxide production which was derived from lactate. These measurements were performed on 16 normal dogs and on 23 dogs in a state of shock. Shock was induced by hemorrhage in ten, by controlled cardiac tamponade in seven and by endotoxin injection in six. In all of the dogs in a state of shock, there was a statistically significant increase in both the arterial lactate concentration and lactate turnover, while the lactate clearance decreased significantly. The percentage of the arterial lactate which underwent oxidation remained normal. The percentage of the total carbon dioxide production which was derived from lactate increased significantly, p less than 0.05, from 4.7 per cent in the normal dogs to 22.7 per cent in the dogs in a state of shock. Since both oxygen uptake and carbon dioxide production remain unchanged in shock, these data are consistent with an increased metabolism of substrates which from pyruvate and lactate as intermediary metabolites, that is, carbohydrates and certain amino acids, with a concomitant decrease in the metabolism of substrates which do not form pyruvate, that is, free fatty acids. In both the normal and shocked dogs, the arterial lactate concentration rose as the lactate production rate increased. Therefore, the elevated arterial lactate in shock was due to an increase in the lactate production and not to a lack of oxygen.


Risk factors in local surgical procedures for diabetic gangrene.

One hundred and seventy-two diabetic patients undergoing local operations of the foot distal to the ankle joint were reviewed to explore the preoperative prognostic indicators of operative failure. Severity of infection, as measured by preoperative temperature and white blood count, correlated with that of failure. Subcutaneous gas, as seen roentgenographically, was associated with failure in five of six patients. No particular operation or type of wound and no general or specific medical or laboratory parameter correlated with failure. In the four and one-half years of the study, an improved operative success rate could only be correlated with improved preoperative management of infection, as reflected in a declining yearly preoperative white blood count and temperature. Delay of the operation until maximum medical control of the infection has occurred should improve the initial success rate in these patients.


Colloid oncotic pressure and levels of albumin and total protein during major surgical procedures.

From the results of this study, it appears that whole blood alone or red blood cells reconstituted with saline solution do not adequately replace the loss of albumin and concomitant decrease in colloid oncotic pressure that occur during extensive intraabdominal and intrathoracic operations. Since colloid oncotic pressure is a major factor in the restitution of intravascular volume from stores of interstitial fluid and since it may also play a role in the development of postoperative pulmonary problems, it is important to maintain a relatively normal colloid oncotic pressure during the operation and in the immediate postoperative period. Although dextran can be used for this purpose, its short half-life of four to six hours and associated coagulation problems militate against its use in large quantities. This leaves purified protein fraction or salt-poor albumin as the main sources of protein for the maintenance of colloid oncotic pressure. Both of these products are expensive and short in supply. The oncometer in present use is a clinically feasible and rapid, one to three minutes, means of determining the colloid oncotic pressure. It permits a rational approach to the use of albumin products, avoiding the pitfalls of under or excess administration in the operative and postoperative periods.


Rapid roentgenologic diagnosis of acute cholecystitis.

A rapid and safe method of roentgenographic evaluation of the acutely inflamed wall of the gallbladder, infusion tomography of the gallbladder, was performed 146 times, and the correlation with 67 subsequent cholecystectomies was reviewed. If the results of infusion tomogram of the gallbladder are abnormal, the gallbladder is diseased; if acute cholecystitis is present, the results of the examination will be abnormal in 96 per cent; if results of the infusion tomogram of the gallbladder are normal, the results are questionable, and oral cholecystography should be performed to evaluate  the condition further. If the results of a repeat dosage oral cholecystogram are abnormal, the gallbladder probably is diseased, even if the results of an infusion tomographic examination of the gallbladder are normal.


Trauma of the bladder.

The records of 98 patients with trauma of the bladder were reviewed. Eighty per cent were injured as a result of blunt trauma, and 72 per cent of these patients had an associated fracture of the pelvis. The most common type of injury was a contusion, followed by an extraperitoneal rupture of the bladder. In all patients, diagnosis was established by the means of a retrograde cystogram. While all patients with intraperitoneal ruptures of the bladder were treated by surgical repair, half of those with extraperitoneal ruptures were successfully managed by catheter drainage alone. Complications of therapy consisted of bacterial cystitis, presumably as a result of catheter drainage.


A simple plethysmographic method for differentiating primary from secondary varicose veins.

Characteristics of venous flow were studied in 81 normal legs and in 98 legs with varicose vein disorders. The change in the volume in the calf after calf muscle contractions was studied using the strain gauge technique with the patients in the erect position. During contractions of the calf muscle, the volume in the calf decreases, chiefly because of reduction of blood volume in the veins. After cessation of the contractions, there is a gradual return of volume to precontraction values. This was measured in seconds and called venous return time and in milliliters times 100 milliliters of tissue-1 times minutes-1 and called venous reflux flow. In normal persons, the venous return time was 21.9+/-6.7 (S.D.) seconds, and in patients with venous disorders, the corresponding time was 6.9+/-2.9 (S.D.) seconds. Venous reflux flow which was inversely correlated with the venous return time was 11.4+/-4.9 and 22.3+/-7.3 (S.D.), respectively. A good correlation was found between venous return time and venous pressure measurements. No age or sex differences were seen. In patients with superficial venous insufficiency, the venous return time and venous reflux time became normal when the diseased portion of the vein was compressed. In patients with insufficient perforating veins or damaged deep vein valves, external compression did not change venous flow characteristics. This indicates that the method can be used preoperatively to differentiate between primary and secondary varicose veins and, thus, influence the type of operation to be performed. The method can easily be applied for clinical purposes.


The effect of hepatic bile on retained common duct stones.

Study of the time interval since cholecystectomy in 91 patients with symptomatic choledocholithiasis who presented after cholecystectomy led to the conclusion that retained common duct stones increase in size with the passage of time. The inference is that, in these patients bile remains supersaturated with cholesterol after cholecystectomy.


Microscopic technique for reversal of vasectomy.

This microscopic technique for reversal of a vasectomy requires intensive training on small animals in the laboratory before it can be attempted on humans. It has assured sperm in the ejaculate of all patients who have sperm in the proximal portion of the vas at the time of vasovasostomy, good sperm count and motility three to five months later in 90 per cent of them and early pregnancy of the spouse in 50 per cent. Longer follow-up periods will be necessary to estimate how high the eventual success rate will be, but it appears at this juncture that this approach is preferable to nonmicroscopic splinting techniques.


Continuous intracranial pressure monitoring: review of techniques and presentation of method.

Continuous monitoring of intracranial pressure has proved to be of value in guiding the treatment of patients with diffuse cerebral trauma or edema. The evolution of monitoring devices is reviewed from simple lumbar puncture through intraventricular, subdural, epidural and external monitoring with progressively more sophisticated equipment. The device reported in detail connects the subarachnoid space to an on-line data reducer that calculates the percentage time the intracranial pressure is in 16 pressure ranges of 5 mmHg each and portrays it on a histogram. The pressure at that moment, the total range of the intracranial pressure, the level of pressure the patient has had for the largest percented of time, and pressure waves, if present, can all be determined by this process.


The femoral nerve traction test with lumbar disc protrusions.

A easily performed test which can be carried out at the patient's bedside has been described. It is referred to as the femoral nerve traction test. Clinical evidence suggests it may have merit as an aid in the diagnosis of disc herniations that affect the upper lumbar spine.


Angiographic demonstration of vertebral osteoid osteoma.

A case of osteoid osteoma in the left lamina of the T-8 vertebra is reported. The roentgenograms of the thoracic spine showed a hyperostotic round mass with associated scoliotic changes and the myelograms revealed complete obstruction of the spinal subarachnoid space. By selective spinal angiography a peculiar ring-like vascular stain was visualized in the area of hyperostosis which may be characteristic of an osteoid osteoma.


Prolonged, profound hypotension produced safely with sodium nitroprusside.

Nine and one-fourth hours of profound hypotension were necessary to accomplish the successful removal of a large arteriovenous malformation from the medial portion of the dominant parietal lobe. The hypotensive agent used was sodium nitroprusside. The removal was associated with a minimal neurological deficit. This is the longest known use of sodium nitroprusside for deliberate hypotension during surgery which emphasizes the safety of this hypotensive technique, provided the total dosage of sodium nitroprusside is reasonable.


Preferential cerebral hypothermia with elective cardiac arrest: resection of "giant" aneurysm.

The technique of preferential cerebral hypothermia is reported in its application to a patient with a "giant" anterior communicating artery aneurysm. The method utilizes elective ventricular fibrillation and differential or "preferential" hypothermia induced by a combination of external skin cooling and perfusion of core organs with 0 degree buffered electrolyte solution. The value of the technique lies in its provision of a period of safe circulatory arrest approaching one hour without the need for anticoagulation, heart-lung bypass, open chest resuscitation or major vessel clamping. Because of the absence of blood flow and because of the clear fluid washout of the cerebral vessels, it was possible to open the aneurysm, evacuate its contents and resect it in several sections. It was not necessary to clip the feeding arteries until all dissection and total removal of the aneurysm were completed. The application of the technique to neurosurgery and cardiovascular surgery is discussed.


Neuroepithelial Cyst of the cerebellar vermis.

A cyst located in the cerebellar vermis and causing obstructive hydrocephalus is described. The wall of the cyst was lined with ciliated and non-ciliated cuboidal epithelial cells which were completely invested by a basement membrane.


Diagnosis of intrathalamic cyst by computerized tomographic scan.

A case of an intrathalamic cyst initially misdiagnosed as a thalamic glioma is reported. It was followed for five years before a computerized tomographic scan led to a correct diagnosis. A simple means of stereotaxically draining the lesion is illustrated.


Arteriovenous malformations of vein of Galen: microsurgical treatment.

The surgical technic used at the neurosurgical clinic in Zürich in eradicating arteriovenous malformations of the vein of Galen is described. It is based on experience with nine cases. The surgical approach is made posteriorly. The right occipital lobe is retracted laterally from the falx cerebri. The multiple feeding vessels demonstrated in the angiogram are occluded; first, on the right side, then the left, and finally beneath the malformation. The draining vein of Galen is not occluded or removed. The use of the operating microscope is essential.


Benign and malignant teratomas in children: analysis of 85 patients.

Teratomas were observed in 85 infants and children. Fifty-eight (68%) were girls and 27 (32%) boys. Site of origin was sacrococcygeal in 55 patients (64.8%), mediastinal in ten (11.7%), gonadal in ten (11.7%), presacral in four (4.8%), retroperitoneal in three (3.5%), and cervical in three (3.5%). Sixty-seven (78.8%) teratomas were benign and 18 (21.1%) malignant. Malignant tumors were noted in 11 of 55 sacrococcygeal (20%), two of ten mediastinal (20%), three of eight ovarian (37.5%), and both testicular lesions. Cervical, retroperitoneal, and presacral tumors were benign. Age at diagnosis (greater than 1 month), presence of symptoms (urinary and colonic obstruction), and serum positive for alpha fetoprotein were indicators of malignancy in sacrococcygeal cases. Age was not a factor for teratomas at other sites. Tumor size, presence of calcification, and gross appearance (cystic or solid) did not relate to the tumor's benign or malignant nature. Three of four presacral tumors were associated with anorectal anomalies. Operative resection is the treatment of choice. Four deaths were related to operative hemorrhage. Four of five survivors with malignant teratoma received radiation and chemotherapy. A more aggressive role for combined adjunctive measures is suggested in cases of malignancy.


Unequal pupils. A flow chart for sorting out the anisocorias.

When anisocoria is present, the ophthalmologist knows that something is wrong. However, location of the lesion and diagnosis of the problem can be difficult. A step-by-step flow chart for diagnosis of unequal pupils is presented, with explantation of various signs and descriptions of appropriate diagnostic tests.


Noninvasive ultrasonic carotid angiography: prospective validation by contrast arteriography.

Pulsed ultrasonic images of the carotid bifurcation in 82 vessels of 43 patients were compared independently with contrast arteriograms for stenosis (by percentage quartiles) or occlusion of the internal carotid artery. All 14 occluded vessels were identified correctly by ultrasound but were visualized on repeat examination. Estimation of percentage stenosis on ultrasonic images agreed with the quartile determination by contrast arteriography in 35 of 68 (51 percent) vessels and was within one quartile of correct interpretation in 48 of 68 (71 percent). The interpretative error of grading stenosis of ultrasonic images was due to vascular wall calcification which inhibited ultrasound transmission. This limitation was overcome by sound spectral (sonographic) analysis of distal internal carotid flow velocity which allowed estimation of stenosis within one quartile of that determined by contrast arteriography in 46 of 47 (98 percent) vessels.


Middle cerebral artery microneurosurgical embolectomy.

Cerebral embolism carries significant mortality and morbidity rates. Middle cerebral artery embolectomies which have been carried out in man with variable results, have been reported by different authors, In order to define a time limit for embolectomies before irreversible damage has been incurred, an experimental embolus model was used in dogs. It was observed that embolectomy carried out at 2, 3, and up to 5 hours after embolism was relatively safe and effective. Beyond 5 hours, embolectomy carried an increased risk of death and morbidity.


The exfoliation syndrome: source of the fibrillar material on the capsule.

A clinical case of unilateral capsular exfoliation syndrome was observed in the previously traumatized eye of a 22-year-old man with a drawn-down pupil. The distribution of material correspond to the folds of the inner surface of contiguous iris. The periphery of the lens appeared free of deposits. These findings contradict previous theories on the source of the fibrillar material from the lens epithelium and indicate that it is derived from the iris pigment epithelium and not from within the lens capsule, although there is no question but that the lens is involved in a similar process, the products of which probably do not reach the lens surface. The unilateral occurrence of the exfoliation syndrome in a traumatized eye of a 22-year-old man is unique and cannot be explained at this time.


Carotid body tumors.

Carotid body tumors are encounterd infrequently. During the past 30 years, 15 patients with 16 carotid body tumors have been treated at our medical center. All patients have been followed for a minimum of 7 years. The major findings relate to the areas of greatest controversy concerning carotid body tumor treatment: the need for excision, the value of preoperative arteriography, the role of radiation therapy, the criteria of malignancy, and the indications for and technique of carotid artery replacement. Discussed at length are our conclusions that (1) arteriography is absolutely diagnostic and therefore mandatory when carotid body tumor is suspected; (2) radiation therapy has little if any value and has increased the difficulty of excision; and (3) all carotid body tumors should be considered to be malignant. The familial tendency of this tumor is explored in relation to this last conclusion, and we report what we believe is the first finding of both a "benign" and "malignant" tumor occurring in the same family. The techniques of subadventitial excision and carotid artery replacement with autogenous saphenous vein, the latter necessary on three occasions, are demonstrated. There were no operative deaths, no serious complications after operation, and no recurrence or metastasis following total excision. However, two patients died as a direct result of tumor growth following biopsy without excision.


Application of contemporary reconstructive techniques in head and neck surgery for anterior oral-facial cancers.

One hundred and seventy-eight patients underwent surgical therapy for oral and cervical cancers from 1964 to 1975. About 25 percent of the patients underwent neck dissection and/or "pull-through" procedures. However, majority of patients required a spectrum of reconstructive techniques extending from marginal mandibulectomy with or without skin flaps (39), partial mandibulectomy with immediate prosthetic mandible reconstruction (36), to extended resections with skin flaps or staged reconstructive procedures (48). The advantages and disadvantages of each reconstructive procedure have been observed and a scheme of graded management has been developed. The therapeutic goal is to maximize functional oral reconstruction without compromising tumor cure. There were two operative deaths--one from myocardial infarction after operation and one from halothane hepatitis. The tumors were grouped according to TNM classification. In the follow-up of the 178 patients, 47 per cent are known to be alive and free of tumor. The better results (greater than 70% free of tumor) are in the group with smaller tumors (less than 2 cm.) and no node involvement, and there are less favorable rates for those patients with larger tumors and nodal metastasis or invasion of adjacent structures. There was a 49 percent 2 year survival rate and 12 of the deaths were from nontumor causes. Ninety percent of these patients smoked more than one pack of cigarettes per day, accounting for the high rate of synchronous or subsequent oroairway cancers (7 percent). Seventy-five percent were considered to be "heavy alcoholics" with evidence of cirrhotic liver disease. These two factors significantly decreased the survival from rate 54 to 47 percent. The series shows that planned primary reconstructive surgery can be done at a low risk, that it can enhance resectability of head and neck cancers, and that it does improve oral function after operation.


Hypercalcemia in patients with known malignent disease.

In 82 patients, a preoperative diagnosis of primary hyperparathyroidism has been established by means of transfemoral neck vein catheterization and measurement of serum immunoreactive parathyroid hormone (iPTH). Twenty-five of these patients have had cancer in other parts of the body but with no evidence of recurrence or metastasis. One patient had carcinoma of the colon with metastases, and four were members of families with multiple endocrine adenomatosis (MEA, Types I and II). In six other hypercalcemic patients, high levels of iPTH were found also in the effluent blood from cancer sites other than the parathyroid gland, secondary to ectopic hormone production or pseudohyperparathyroidism. In addition, a high serum level of iPTH was found in the superior vena cava of a seventh patient who had carcinoma of the breast but no clinical or radiological signs of recurrence or metastasis with the exception of an enlarged liver. This iPTH finding was interpreted as being, probably, the result of parathyroid adenoma in either the neck or the mediastinum. At the time of operation, a transcervical mediastinal search was made. Four normal cervical parathyroid glands were found; three were removed. Hypercalcemia persisted after operation, and the patient died. At postmortem examination, microscopic study revealed that the disease had metastasized to lungs and hilar lymph nodes. There was massive metastasis in the liver; the liver contained a large amount of iPTH. The results of these investigations suggest that (1) venous catheterization of the neck veins and the effluent blood from extraparathyroid tumors aid in identifying and localizing iPTH production; (2) primary benign hyperparathyroidism is not uncommon in patients with cancer, and its co-existence must be recognized; (3) high serum iPTH level in the superior vena cava may be found in patients with metastatic or primary cancer of the thoracic cavity; and (4) hyperparathyroidism may be the first hint of a familial multiple endocrine syndrome.


Myopia--a treatable "disease"?

The authors cite various information and misinformation regarding proposed treatments (atropinization, contact lenses, orthokeratology, wearing glasses, not wearing glasses) for the progression of myopia. They conclude that there is insufficient evidence to support the more vigorous approaches to treatment of myopia, and provide some useful explantations for patients and their parents who question the ophthalmologist's decision to treat conservatively.


Long-term follow-up of peptic strictures managed by dilatation, modified Collis gastroplasty, and Belsey hiatus hernia repair.

Between 1964 and 1974, 277 patients with peptic esophagitis were managed by modified Collis gastroplasty and Belsey hiatus hernia repair. By adding a gastroplasty in patients with esophageal shortening, an antireflux repair can be done below the diaphragm, with elimination of tension on both the repair and the intrathoracic esophagus. Indications for repair in this series were peptic strictures, 102; recurrent hiatus hernia, 90; panmural esophagitis with stricture, 44; and reflux esophagitis associated with primary motor disorders, 41. Results of treatment are being evaluated by clinical history, esophagography, esophagoscopy and manometry; and generally they appear to be excellent. However, follow-up is too short in many of these patients to permit meaningful evaluation. A more critical analysis is provided by long-term follow-up of patients with the most severe pathology. This report reviews results in the 33 patients in the series, with peptic strictures, operated on more than 5 years ago. Five of the 33 patients died of unrelated disease before reaching their fifth year after operation, and two were lost to followup. Twenty-six patients have been followed 5 to 12 years since operation. Twenty-five patients had excellent results which were sustained during the period of follow-up. They take a regular diet without dysphagia, and none has symptomatic reflux. One patient, whose symptoms initially resolved, developed recurrent reflux due to peptic ulceration and pyloric stenosis. The functional results achieved with this operation are good and are maintained well beyond 5 years. Results reported with alternative, conservative operations for peptic stricture are reviewed.


Teratogenicity studies with methotrexate, aminopterin, and acetylsalicylic acid in domestic cats.

Pregnancy was timed in cats following induced ovulation. Methotrexate, (0.5 mg/kg), aminopterin, (0.1 mg/kg), and acetylsalicylic acid, (25 or 50 mg/kg) were administered orally in gelatin capsules in single daily doses on different days of gestation, methotrexate (MTX) on days 11-14, 14-17, or 17-20, aminopterin on day 12, 14, or 16, and acetylsalicylic acid (ASA) on days 10-15 or 15-20. Maternal toxicity was produced only by MTX. MTX given on days 11-14 and 14-17 produced high frequencies of malformations including umbilical hernia. Aminopterin caused no conclusive teratogenic response. An overall increased frequency of anomalies occurred after 50 mg/kg ASA but no single anomaly predominated.


Test of the hypothesis that embryonic face shape is a causal factor in genetic predisposition to cleft lip in mice.

It was proposed that embryonic face shape is one of the quantitative variables underlying the threshold trait, cleft lip. To test the hypothesis several facial dimensions were measured in photographs of embryos at an early stage of formation of the face in 3 lines of mice. The lines had been selected from one original population using frequency of cleft lip induced by 6-aminonicotinamide as the selection criterion. Line L was susceptible to spontaneous cleft lip; lines M and C were not. Line L had a significantly smaller distance between the nasal pits than the other 2 lines, but did not differ in overall head size. A trend towards reduced angle between the medial nasal processes in the L line was noted, though this was not statistically significant. These results were predicted by the face-shape hypothesis.


The teratogenic effects of beta-aminopropionitrile in hamsters.

The teratogenicity of beta-aminopropionitrile (beta APN) was evaluated in golden Syrian hamsters; single doses of 1250, 2500, and 3750 mg/kg given on days 7-13 produced fetal mortality, growth retardation and malformations. All time-dose combinations produced gross external abnormalities with the highest rate (92.5%) occurring following day-12 treatment. High frequencies of skeletal abnormalities including deformities of the ribs, fibula, and scapula occurred after days-10-12 treatment. Deformed ribs occurred in 100% of fetuses exposed on day 11 to any of the dosages. The types of abnormality generally resembled those produced by lathyrogens in other species except for exencephaly and encephalocele, which occurred after treatment on day 7. These results indicate that betaAPN is a typical teratogen, capable of producing abnormalities of the central nervous system early in gestation, and may reflect a broader mechanism for its activity than previously suggested.


Transplacental passage of label after administration of (3H) retinoic acid (vitamin A acid) to pregnant mice.

To determine whether there is transplacental passage of retinoic acid (vitamin A acid) or its metabolites levels of radioactivity were measured in embryos after administration to 12th-day pregnant ICR/DUB mice of nonteratogenic or teratogenic quantities of (3H)retinoic acid. After the former treatment radioactivity was demonstrable in embryos, placentas, and visceral yolk sacs (VYS) at 1 h after treatment. Expressed in terms of radioactivity per unit protein content, embryos at 1 h had about one-third as much radioactivity as maternal livers. The placentas had maximum radioactivity at 2 h, whereas embryos and VYS accumulated maximum levels by 6 h after treatment. At 6 h the level in embryos was twice that in placentas. After teratogenic treatment placentas and embryos attained peak levels of radioactivity at 6 and 12 h later, respectively. Again, embryos at peak level contained 2-3 times as much radioactivity as placentas or VYS. The amount of retinoic acid, metabolites, or both, in embryos after the teratogenic treatment, calculated on the basis of specific activity of the injected label, was 26 times greater than after nonteratogenic treatment; the amount in maternal liver was 75 times greater. The results support previous evidence that the teratogenic effects of retinoic acid are associated with raised levels of retinoic acid, its metabolites, or both, in embryos.


In vitro development of postimplantation rat embryos cultured on dialyzed rat serum.

Attempts to culture postimplantation rat embryos on defined media have not been successful although they grow well when cultured on homologous serum. As a first step in the search for factors in serum that support growth and differentiation of such cultured preparations the following experiments were undertaken. Six-somite rat embryos were cultured on whole serum, dialyzed serum, or the buffered salt solution (BSS) used for dialysis. Additional experiments were conducted utilizing BSS supplemented with glucose or dialyzed serum supplemented with glucose, mannose, fructose, or pyruvate. Of the media tested only glucose-supplemented dialyzed serum maintained development at a level comparable to that obtained with whole serum. Further preliminary studies with combined supplementation and metabolic poisoning suggested that anaerobic glycolysis is essential for the in-vitro growth and differentiation of these preparations.


Studies of the etiology of thalidomide dysmorphogenesis.

Thalidomide was administered to pregnant rabbits in dosages of 150-250 mg/kg/day on days 8-12 of gestation. These females produced 40 offspring, 21 of which were deformed. Four control females produced 34 offspring, none of which was deformed. The C6 and C7 ganglia of day-13, -15, -17, and -21 control and experimental embryos and fetuses were examined electron microscopically. Degenerative changes were found in the neurons and axons of dorsal root ganglia in day-13 experimental embryos, i.e., at least 16h before the earliest signs of thalidomide dysmelia have been reported in rabbits  (Vickers, '67). Since the dorsal root ganglia form in rabbits on days 11 and 12 the changes evident at day 13 indicate that degeneration of neurons and axons may be a pathogenetic factor in thalidomide-induced peripheral deformities.


Neural-tube defects caused by 5-bromodeoxyuridine in chicks.

Chick embryos were explanted at HH stage 4 and cultured for 24 h on thin albumen with 10 mug/ml 5-bromodeoxyuridine (BrdU). BrdU inhibited closure of the neural tube in over 90% of the embryos. Mitotic figures were found throughout adversely effected neuroepithelium, suggesting that interkinetic nuclear migration had been inhibited. Electron microscopic studies of BrdU-treated neural-tube cells showed fewer and more amorphous cytoplasmic extensions, microfilaments, and demosomal (juctional) tonofibrils than in controls, but microtubules were unaffected.