Post-mortem changes in the rabbit retina. A study by light microscopy. The course of post-mortem changes in rabbit retina has been followed. Short post-mortem periods are accompanied by degenerative changes limited mainly to the visual cells and retinal pigment epithelium. Long post-mortem periods are associated with degenerative changes throughout the retina. Retinal tissue maintained at room temperature was less affected than that kept at body temperature (37degreesC). Post-mortem changes are similar to those observed following periods of pressure induced ischaemia and it is thought that the mechanical effects of pressure on retinal tissue are minimal at the level of resolution afforded by light microscopy.


Retinal functions in dominant cystoid macular dystrophy (DCMD). Dominant cystoid macular dystrophy (DCMD) occurred in 28 members of 5 unrelated families. The disease is characterized by cystoid macular oedema and leakage from retinal capillaries in the posterior pole. Colour vision examination reveals a type I red-green defect with concomitant blue-yellow defectiveness; the latter may be caused by the leaking capillaries. The ERG is normal. The EOG is subnormal. Darkadaptation curves are often slightly disturbed. There are frequently also aspecific pigmentary alterations in the peripheral fundus.


Atrophy of optic nerve fibres in compression of the chiasm. Degree and distribution of ophthalmoscopic changes. Chiasmal lesions produce a characteristic form of partial optic atrophy, subtly reflected by objective changes in the peripapillary portion of the retinal nerve fibre layer. The degrees and distributions of these changes were documented by fundus photography in a series of steady state patients with different degrees of chiasmal damage from pituitary adenoma. Semi-quantitative analysis disclosed a close correspondence with the degree of functional deficit. The state of the retinal nerve fibre layer can therefore be used as an objective indicator of the occurrence and severity of anatomical, chiasmal damage.


Vogt's retro-iridian pigment lines. Light microscopical and ultrastructural study of a case. A woman, aged 69, with latent diabetes was found to have retro-iridian pigment lines. Cataract extraction was followed by light microscopy and electron microscopy. Cross sections of the pigment lines showed these to consist of two main constituents, whose structures are described. The portion of the lines closest to the lens had a certain resemblance to the substance seen on the lens and in the iris in pseudo-exfoliation, while the remaining part of the pigment lines consisted of uniform microtubules.


Aneurysmatic dilatation of the duodenum and a nephrointestinal fistula in a case of abdominal lymphoma. A 73-year old woman presented with malaise, weight loss and urinary tract infection. Aneurysmatic dilatation of the duodenum and a nephrointestinal fistula were radiologically demonstrated. The two, very rare phenomena coincided in one patients and were due to abdominal lymphoma.


The cyclopentolate provocative test in suspected or untreated open-angle glaucoma. III. The significane of pigment for the result of the cyclopentolate provocative test in suspected or untreated open-angle glaucoma. Significant elevations of IOP, i. e. responses, occurred in eyes with suspected or untreated open-angle glaucoma during the mydriasis test with 1% cyclopentolate (CPT). The possible role of pigment in the IOP elevations seen in the responders was studied. Pigment was liberated in the aqueous, sometimes very profusely, in 88 (31.9%) of 276 eyes during CPT. The maximal IOP elevations, ad 20 mmHg, were seen in just these eyes. They were eyes with capsular or pigmentary glaucoma or eyes in which exceptionally heavy pigment was demonstrated in the chamber angle for other reasons. There was a statistically significant correlation between pigment liberation and IOP elevation during CPT. Evidently profuse pigment liberation may have caused transient blocking of the trabecular meshwork, obstruction of aqueous outflow and elevation of IOP. Liberation of pigment in the aqueous during CPT was statistically highly significantly more profuse in eyes with pseudoexfoliation than in eyes without pseudoexfoliation. An equally significant correlation with demonstrated between the grade of chamber angle pigmentation and the degree of pigment liberation during CPT. The significance of pigment for IOP elevation was seen also in the statistically highly significantly more profuse pigmentation of the chamber angle in the responder than in the non-responder eyes.


Concentrations of some ribonucleotides, L-lactate, and pyruvate in human senile cataractous lenses with special reference to anterior capsular/subcapsular opacity. The concentrations of some ribonucleoside tri- and diphosphates, adenosine-5'-monophosphate, L-lactate and pyruvate were determined in human senile cataractous lenses removed during cataract operations. Pyruvate concentrations were found to be negligible (median = 56 mumol/kg lens wet weight) in 15 human senile cataractous lenses. On the basis of correlations between the biomicroscopic appearances of the senile cataractous lenses (N = 80) and the concentrations and ratios of the metabolites in question, the following classification was found to be justified: 1. Immature cataractous lenses without anterior capsular/subcapsular opacity: high levels of ribonucleoside triphosphates (RTP), high sums of RTP, ribonucleoside diphosphates (RDP), and adenosine 5'-monophosphate (AMP) as well as high levels of L-lactate and high ratios of L-lactate in the lens/L-lactate in the aqueous. 2. Immature cataractous lenses with anterior capsular/subcapsular opacity; intermediate levels of RTP, intermediate values for the sums of RTP, RDP, and AMP, high L-lactate levels, and intermediate values of the ratios of L-lactate in the lens/L-lactate in the aqueous. 3. Totally opaque lenses, which all had extensive anterior capsular/subcapsular opacity; low values for the concentrations of lens RTP, for the sums of RTP, RDP and AMP, and for lens L-lactate. Low ratios of L-lactate in the lens/L-lactate in the aqueous.


Embryonal sarcoma of the orbit. A clinical review of 19 Danish cases. The present study deals with 19 Danish cases of embryonal sarcoma of the orbit. Eight patients are still alive, however, only six with long-period survival (8-21 years). The contralateral orbit (and eye) remained uninvolved in the 19 cases; accordingly the six long-period survivors all have normal "social" vision. In 17 cases the homolateral eye was removed early or late in the clinical history. Only one of the long-period survivors has preserved the homolateral eye (and with useful vision, 6/24 after surgery for irradiation cataract). The nation-wide investigation covers a period of 22 years. It reflects the difficulties in diagnosing orbital tumours and the changes in therapeutic approach to date. Megavoltage radiotherapy plus chemotherapy immediately after the initial biopsy is now considered the therapy of choice; exenteration of the orbit is performed only in the case of a recurrence. Against the background of the present and an earlier study, centralization of Danish orbital malignancies in infants and children is advocated.


Ocular hypertension. I. The clinical course during ten years without therapy. Aqueous humour dynamics. An initial group of 152 subjects with moderate ocular hypertension constituted the basic material of the present study. Antiglaucoma treatment was started in 8 men and in 6 women. A remaining group of 92 subjects were kept under clinical observation for ten years without antiglaucomatous therapy and without any evidence of progressive disc cupping or field defects. The intraocular pressure as well as the outflow facility showed a tendency to decrease with time, which was assumed to indicate a reduction in aqueous flow with increasing age. The tomographic findings support the view that the moderately elevated intraocular pressure is mainly due to an increased rate of aqueous flow.


Effect of the length of wear of contact lenses on corneal sensitivity. Corneal touch thresholds (CTT) were determined once in the morning before inserting contact lenses then after 4, 8 and 12 h of continuous wear. Two groups of subjects participated in this study; 12 persons wearing hard contact lenses and 15 wearing soft contact lenses. All subjects were perfectly adapted to their contact lenses and had worn them for not less than three months. It was found that hard contact lenses caused a progressive diminution of corneal sensitivity. After 12 h corneal sensitivity was, on average, 110% lower (that is an increase of the threshold) than in the morning. Soft lenses also caused a progressive reduction of corneal sensitivity which after 12 h wear was, on average, 45% lower than in the morning, although there were marked differences. Moreover, 9 of the hard contact lens subjects had been tested a year earlier and it was found that their CTT after 8 h wear had slightly but not significantly diminished which indicated that these subjects had not adapted significantly to their lenses in one year.


Freeze-fracture replica of the rat cornea. The fine structures of the rat cornea, with special reference to their intercellular junctions, were studied using the freeze-fracture technique. At the corneal epithelium, gap junctions could be observed between the adjacent cells. At the stroma, crater-shaped depressions (between 300 and 500 A diameter) with pipe-like appearing structures connecting the lamellae were found. Intercellular junctions existing between the endothelial cells at the area near the anterior chamber are postulated to be the fascia (macula) occludens.


Orbital involvement by plasmacytoma.  Report of two cases. Two patients with orbital involvement of plasma cell myeloma are presented. The first patient presented an isolated plasmacytoma in the orbit; the second patient had generalized plasma cell myeloma. In both cases X-rays and computed tomographic scanning gave valuable information and biopsy confirmed the diagnosis.


Unilateral proptosis due to midbrain tumour. A case report. A case of unilateral proptosis attributed to midbrain tumour is reported. The proptosis disappeared after release of intracranial hypertension. The postulated mechanism of the unilateral proptosis on the left side is a relative increase in orbital venous stasis on that side, consequent upon intracranial hypertension.


Orbitography with a new non-ionizing water-soluble contrast medium. Metrizamide is a non-ionic water-soluble contrast medium which is isotonic with human blood and tissue fluid at a concentration of 170 mgI/ml. Retrobulbar injection of 3 ml isotonic metrizamide in the muscular conus of rabbits causes slight and inconstant cellulitis, but a similar reaction can also be found after injection of the same amount of saline. It seems probable that the introduction of fluid sufficient to cause an increase in the retrobulbar pressure can cause inflammatory changes in the orbital tissue, and that this is not always caused by the contrast medium itself. Four patients were examined by orbitography with injection of 4 ml isotonic metrizamide. There were no side effects, and the orbitograms showed contrast of good quality. Metrizamide is therefore considered very suitable for orbitography, especially in hospitals where computer-tomography is not yet available.


Further data on biometric correlations of central corneal thickness. Central corneal thickness measured in 126 young men aged from 18-21 years was correlated to a number of ocular and other parameters. The frequency distribution was skewed towards the lower end, but the deviation could not be statistically supported. No correlation between corneal thickness and birth weight was found. Other characteristics not correlated in this material to corneal thickness were corneal astigmatism, refraction, visual acuity, optic disc and retinal abnormalities, red-green colour vision defects, ABO and rhesus blood-groups, EEG abnormalities, chromosomal abnormalities, hearing defects, ear abnormalities and quality of the hair. The findings in this study, although mainly of negative character, stress the relative independence of the central corneal thickness as a biometric parameter.


Transient glaucoma as a manifestation of mumps. A case report. A case report of a 43-year-old man who during convalescence after mumps (parotitis epidemica) developed bilateral glaucoma associated with redness of his eyes but no other ocular manifestations. The chamber angles were open. No signs of scleritis or iritis were present. The best treatment was found to be prednisolone topically and acetazolamide orally. After ten days the intraocular pressure was normalized and after a fortnight all treatment could be discontinued.


The cyclopentolate provocative test in suspected or untreated open-angle glaucoma. IV. Fluorescein angiography of the vessels of the iris in open-angle glaucoma eyes with a positive cyclopentolate response. Fluorescein angiography of the iris (IFAG) was performed on 15 patients with a positive cyclopentolate response (IOP elevation greater than or equal to 8 mmHg) in 17 eyes to the cyclopentolate provocative test. The chamber angles were open in all the eyes. Seven of the responder eyes had capsular glaucoma undergoing treatment, six had simple glaucoma, two had pigmentary glaucoma and two suspicion of open-angle glaucoma. The object was to study with IFAG whether vascular changes can be established in the iris of the responder eyes such as could have a role in the elevation of IOP. All the eyes with capsular glaucoma displayed vascular changes, vasoproliferation and fluorescein leakage from the iris vessles. No other vascular changes were seen in the irises of the responder eyes. IFAG revealed no differences in the iris vasculature between responder and non-responder eyes. A vascular aetiology for the IOP elevation in responders is improbable.


The cyclopentolate provocative test in suspected or untreated open-angle glaucoma. V. Statistical analysis of 431 eyes. The mydriasis provocative test with 1% cyclopentolate (CPT) was performed on 431 eyes with suspected or untreated open-angle glaucoma. Tonography was performed both before and during CPT to study the changes in aqueous dynamics during the test. Statistical analysis of the results yielded the following mean trends and correlations at a highly significant level (P less than 0.001) in the alterations: Intraocular pressure (IOP) rose (deltaP +/- SD) (+ 1.4 +/- 2.9 mmHg) and aqueous outflow facility decreased (deltaC) (-10%) during CPT. The distribution of deltaP and deltaC did not follow the normal Gaussian distribution. The change in deltaP deviated from the Gaussian distribution in 5-10% of the eyes. The deviating values concur with those of the responder eyes in which IOP rose greater than or equal to 8 mmHg during CPT. deltaP was linearly dependent on the initial IOP level Po and the absolute change was always almost constant, approximately +1.4 mmHg. Both the total series and the responder eyes displayed the same trend for the change in aqueous outflow facility in relation to the initial C value (Co): low Co values changed less on average and high Co values changed more and diminished. It is not known why the deltaC change was different depending on the Co value. The change in IOP correlated statistically highly significantly in the initial C value (Co). The loqwe the Co value, the higher was the mean IOP elevation during CPT. In contrast, the change in aqueous outflow (deltaC) did not corrrelate (N.S.) with the initial IOP level (Po) before CPT.


The variation and covariation of cup and disc diameters. The variation and covariation of cup and disc diameters were studied in a material derived from a population survey and consisting of 2,334 fundus photographs from as many eyes in 1,322 subjects. A simple device was used to facilitate focusing of the camera. The colour slides were projected on to a screen at a fixed distance and measured on ruled paper. The effect of refraction on the magnification in the eye-camera system was compensated by the use of a simple correcting factor. Some apparently quite normal discs, nevertheless, had an area more than four times larger than that of other equally normal ones. The sizes of discs and cups covaried, however, to a suprisingly great extent (r = 0.8) and changes in disc diameter were in general parallelled by similar changes in cup diameter. The amount of tissue in the optic nerve head therefore varied somewhat less than the disc size. Cup diameters were widely dispersed, unevenly distributed and heavily dependent on disc size. The "average rim breadths", on the other hand, were much less dispersed, normally distributed and independent on the disc diameter. By taking the covariation of cup and disc diameters into account the detection of any enlargement or diminution of the optic cup ought to be facilitated.


Peripheral visual field restriction in chloroquine retinopathy. Report of a case. Chloroquine compounds are known to cause a retinopathy which typically begins in the central fundus giving rise to a "bull's eye" macula. Ultimately peripheral changes may become apparent. In the routine eye examination of such patients emphasis has been laid on the central area of the fundus. A case is presented where the retinopathy was not diagnosed until marked peripheral changes had occurred with peripheral pigment changes, attenuated retinal vessels, slight optic atrophy, peripheral visual field restriction and a subnormal electroretinogram. The typical "bull's eye" changes were not apparent. Routine examination of the peripheral fundus by means of ophthalmoscopy and perimetry is necessary to avoid missing any such retinopathy.


Temporal lobe epilepsy and neuro-ophthalmology. Ophthalmological findings in 74 temporal lobe resected patients. A survey is presented of the ophthalmological findings in 74 patients with drug-resistant temporal lobe epilepsy, who underwent unilateral anterior temporal lobectomy 1960-1969 at Rigshospitalet, Copenhagen. At follow-up, 1970-1971, one to ten years following the operation, 81% of the patients had no or only few seizures. Preoperatively 11% of the patients suffered from strabismus as compared to an expected frequency of 5%, but this trend just falls short of statistical significance. The visual acuity remained unchanged in all patients following the operation. Preoperatively a visual field defect was observed in 2 patients. At follow-up 51 patients had homonymous hemianopias, in 38 of them this was limited to the upper quadrants, and in 13 patients also included the lower quandrants, but was characterized as a total homonymous hemianopia in only 6 patients. The presence and extent of the visual field defects were correlated to surgical results, age at onset of epilepsy, age at operation, preoperative duration of epilepsy, presence of grand mal, preoperative complications, and neuropathological findings, but without observing any statistically significant conclusions. On the other hand, the extent of the postoperative visual field defect was significantly influenced by the side of the operation, with more and larger defects following right-sided lobectomies. In the 51 patients with postoperative hemianopias, this defect was either unobserved by the patient or regarded as a considerably less important handicap than the frequent and socially invalidating preoperative seizures...


Investigations on the antihypertensive activity of timolol and bendroflumethiazide and the combination in dogs and rats. The effects of timolol and bendroflumethiazide, either alone or combined in a fixed ratio of 4:1, on blood pressure, plasma renin activity, and plasma potassium concentration, have been investigated in normotensive and renal hypertensive dogs, and in normotensive and spontaneously hypertensive rats. In addition, the urinary kallikrein excretion has been measured in normotensive and hypertensive rats. When administered to hypertensive dogs and rats, the drug combination significantly reduced the blood pressure. Marginal reductions were observed in normotensive animals or after the administration of the single drugs. The thiazide-induced hypokalaemia and hyperreninaemia were almost completely antagonised by the concomitant administration of timolol in both animal species. A highly significant elevation of urinary kallikrein excretion was also observed in rats treated with the drug combination. A less marked increase of kallikrein excretion was noted in the bendroflumethiazide treated rats. The possibility that renal haemodynamic changes, in addition to the inhibition of the increase in plasma renin, play a role in the observed antihypertensive effects is discussed.


Effect of pyrazole, 4-methylpyrazole, 4-bromopyrazole and 4-iodopyrazole on brain noradrenaline levels of mice and rats. Four daily doses of pyrazole (50 mg/kg), caused a reduction in rat brain noradrenaline (NA) of over 20% when determined 24 hrs after the final injection. Neither 4-methylpyrazole (10-50 mg/kg), nor 4-iodopyrazole (10-50 mg/kg) had any effect. In mice treated similarly, pyrazole (50-400 mg/kg) caused a dose-dependent decrease in brain NA. Neither 4-methylpyrazole, 4-bromopyrazole nor 4-iodopyrazole caused any significant change in the levels. However if the brain NA levels were examined 6 hrs after a single dose, then in addition to pyrazole, 4-methylpyrazole showed a dose-dependent ability to lower brain NA. 4-bromopyrazole and 4-iodopyrazole, given acutely, caused a dose-dependent decrease in rectal temperature and exploratory behaviour. 4-methylpyrazole in high doses (200-400 mg/kg) showed similar properties but they did not correlate with the decrease in brain NA. Pyrazole, after acute treatment, showed little ability to change rectal temperature of exploratory behaviour. It is concluded that the NA-depleting effect of pyrazole is not related to inhibition of alcohol dehydrogenase, since other 4-substituted pyrazoles which are more potent inhibitors of the enzyme have little or no effect on brain NA levels.


Studies on the metabolism of Orange Rn in the pig. Orange RN (monosodium salt of 1-phenylazo-2-naphthol-6-sulphonic acid) was administered to female pigs either by intraveneous injection or by stomach tube. After intravenous injection of Orange RN, 7.8 mg/kg, the following metabolites were indentified in 24-hour urines: Orange RN (31%), 1-(4-hydroxyphenlazo)-2-naphthol-6-sulphonic acid (3%), p-aminophenol and 0-aminophenol (34% and 4% of the theoretical yield, respectively). 1-Amino-2-naphthol-6-sulphonic acid was present, but not determined. When the urine collection was extended to 72 hours the excretion of p-aminophenol accounted for the remainder of the phenylazo moiety. The excretion pattern for p-aminophenol suggest that Orange RN is partly excreted in the bile and thereafter undergoes azo reduction in the gut. After administration of Orange RN, 78 mg/kg, by stomach tube the following metabolites were identified in the urine: Total coloured metabolites (Orange RN and 1-(4-hydroxyphenylazo)-2-naphtholphenol-6-sulphinic acid) (0.4% of the theoretical yield), p-aminophenol and o-aminophenol (52% and 6% of the theoretical yield, respectively) and aniline (0.3% of the theoretical yield). 1-Amino-2-naphthol-6-sulphonic acid was present, but not determined.


Effects of aminooxyacetic acid and baclofen on catalepsy, striatal homovanillic acid increase and antinociception caused by methadone in rats. The effects of aminooxyacetic acid (AOAA) and baclofen on the catalepsy, striatal homovanillic acid (HVA) increase and antinociception caused by methadone were studied in rats. Antinociceptive responses were tested by the electric foot-shock method. A new type of stimulator unit which delivered nearly constant current over a wide range of output voltage and which was noiseless was designed and its construction is described. AOAA (25 mg/kg) which increases the cerebral concentration of gamma-aminobutyric acid (GABA) and baclofen (10 mg/kg), a structural analogue of GABA, did not change the catalepsy induced by methadone (5 mg/kg). AOAA (25 and 50 mg/kg) alone did not alter the striatal HVA content and had no effect on the methadone induced HVA increase. Baclofen (10 mg/kg) increased the striatal HVA content by 19% (P less than 0.01) and reduced the methadone-induced HVA increase by 36% (P less than 0.01). AOAA (25 mg/kg). These results suggest that narcotic analgesics might cause catalepsy and increase striatal dopamine turnover by some other mechanism than neuroleptics. The results support the suggestion that GABA might be involved in pain mechanisms.


Effect of manganese on the levels of DNA, RNA, DNase and RNase in cerebrum, cerebellum and rest of brain regions of rat. Levles of DNA, RNA, DNase, RNase and manganese in different regions of rat brain were studied after daily administration of manganese chloride (8 mg MnCl2-4H2O/kg intraperitoneally) for a period of 120 days. DNA and RNA contents decreased significantly in cerebrum, cerebellum and rest of the brain regions after manganese treatment. A decrease in the DNase and an increase in the RNase activity was observed in the cerebellum and rest of brain region of the manganese treated animals. The manganese content increased significantly in all the regions of the brain, the maximum concentration being in the rest of brain portion. The presence of excess manganese in brain presumably leads to alterations in the functional activity of lysosomal enzymes. The decrease in the levels of nucleic acids is perhaps a consequence of the degenerating and dead neurones.


Auto-immunity in certain thyroid diseases. In the years 1971-74, 88 patients were admitted to the Department of Otorhinolaryngology of the Finsen Institute because of thyroid disease. In 37 of these patients, who had also been tested for antibodies against the thyroid, the diagnosis was confirmed histologically. The existence of circulating antibodies against thyroid tissue was found to reflect the degree of lymphocyte infiltration in the thyroid gland, and is thus of significance in the evaluation of the patients' prognosis and potential risk at surgery.


Ventricular electrical instability in the conscious dog: effects of psychologic stress and beta adrenergic blockade. The effect of psychologic stress on cardiac vulnerability was examined in 10 conscious dogs. The repetitive extrasystole threshold was employed as a measure of susceptibility to ventricular fibrillation. Instrumental aversive conditioning constituted a stressful environment. The repetitive extrasystole threshold decreased by nearly 50 percent during 3 days in which the animals were exposed to the stressful environment. When Tolamolol hydrochloride, a cardioselective beta adrenoceptor blocking agent, was administered before a stress session, the repetitive extrasystole threshold was unaltered from the control value. Thus, stress-evoked changes in cardiac vulnerability are mediated through the sympathetic nervous system.


Infected atrial myxoma.

Infected atrial myxoma. A patient with an infected atrial myxoma presented with clinical findings simulating bacterial endocarditis. The diagnosis was made with echocardiography, thus demonstrating the value of this rapid, noninvasive screening test. A ruptured mycotic aneurysm in the brain precluded early surgical excision of the tumor. The rapid evolution of this case to a fatal outcome underscores the need for prompt diagnosis.


Antidotal efficacy of activated charcoal in presence of jam, starch and milk. The effect of addition of jams, marmalades, starches and milk products on the adsorptive capacity of activated charcoal for acetylsalicyclic acid was determined in vitro. The addition of these products to an aqueous suspension of activated charcoal decreased the adsorption of acetylsalicylic acid from 98% to 95% or 90% (jams and marmalades) or to 80% (milk). Starches had no effect. It appears that the use of jams to make ingestion of activated charcoal easier is acceptable.


Induction of menstruation with bromocryptine in patients with euprolactinemic amenorrhea. Three nulliparous women presented with secondary amenorrhea with no evidence of endocrinopathy and normal skull x-ray. Pulsatile gonadotropin secretion was reduced, but an adequate pituitary gonadotropin reserve was demonstrable with luteinizing hormone-release factor provocation. The administration of bromocryptine was associated with amplification of pulsatile secretion of gonadotropins and was followed, in two of the three, by ovulatory menstruation. It is suggested that bromocryptine should be considered for induction of menstruation in euprolactinemic secondary amenorrhea.


[Pulmonary surfactant in neonatal pathology]. Following some preliminary remarks on the role of the surfactant in pulmonary physiology and physiopathology, a physiochemical study of the lungs of 26 infants who died in the neonatal period is reported. Two techniques for measuring the decrease in surface tension are set out. The results in the first case (tensiometric method) allow an explanation of the physiopathological aspect of respiratory distress; in the second case (manometric method) the diagrams obtained are characteristic of different clinical states (normal subjects; subjects born prematurely without any hyaline membrane etc...). Furthermore, the second method gives rise to certain hypotheses as to the physiochemical structure of the substances responsible for the tensio-active properties of the surfactant.


Allergic contact dermatitis from ethyl sebacata in haloprogin cream. A 13-year-old girl developed contact dermatitis to haloprogin (Halotex) cream. Patch tests incriminated ethyl sebacata, a solubilizer, as the allergen. To our knowledge, this is the second reported case of contact dermatitis attributable to this substance.


Systemic methotrexate toxicity. A pharmacological study of its occurrence after intrathecal administration in a patient with renal failure. Methotrexate pharmacokinetic studies, performed on a patient with renal impairment who had toxic effects following 20 mg/sq m of intrathecally administered methotrexate, demonstrated prolonged serum concentrations of the drug, which accounted for the condition. After the return of normal renal function, pharmacokinetic studies were repeated following the same dose and route of administration of methotrexate. On this occasion there was a rapid clearance of serum methotrexate below toxic levels.


[Gonadal function of rats following pre- or postnatal administration of some hormones (author's transl)]. Some steroid hormones as well as clomiphene have been administered to new-born rats (postnatally) or to pregnant rats (prenatally) in order to study the effect on the future gonadal function of the animals born before or after the injection. A single postnatal androgen injection in oily solution influences only the female function; estrogen or the combination of androgen and estrogen are effective in both sexes preventing the ovulation or damaging the testicles. If the hormone is administered in water instead of oil, several injections are necessary in order to obtain an effect. Only the aqueous solution of clomiphene produces a positive effect even given in a single injection. When a single postnatal injection is effective the same result can be obtained after prenatal administration but only following intraamniotic injection. Clomiphene is an exception to this rule; intraamniotic injection has no effect. These observations permit the following conclusions: 1. It is possible to influence the hypothalamus-hypophysis function not only in the first days of life but already in the prenatal period. 2. As androgen damages only the ovary, estrogen however the gonads of both sexes, the mechanisme of action can not be the same. Androgen alters the function of the sexual centres in the brain only in the female rat, estrogen paralyses this function in both sexes. 3. Prenatal injection of hormone is only effective if administered intraamniotically (eliminating in this way the action of the placenta). This proves the important role of the placenta in the metabolisme of the hormones. 4. Other possible consequences of postnatal androgen administration as permanent obstruction of the vagina or hypertrophy of the clitoris can be obtained equally by prenatal intraamniotic injection. These phenomena can also occur independent of the avarian processes, being due to direct hormonal action. 5. Tubo-ovarian inflammation and abscesses are observed with relative frequency especially following estrogen or clomiphene-administration. The cause is unknown but we can assume that circulatory disorders in the genital area, produced by the hormone, are responsible for the frequency of these phenomena.


[The glycogen content of blood and uterine tissue in women with myoma and endometriosis (author's transl)]. The amount of glycogen in venous blood and uterine tissue from 135 women undergoing gynecologic surgery was quantitatively determined. One group had myoma (n = 48), another endometriosis (n = 30). 18 women had myoma combined with endometriosis of the myometrium. 39 women served as control group. The following samples of the uterus were obtained immediately after removal: endometrium, myometrium, cervix and "tumour". The glycogen content in pathological cases was compared to normal tissue of comparative endocrine state, parity status and glucose tolerance. The significance levels were determined by standard analysis of variance and "t" tests. In the group with endometriosis, a significant difference occurred in the amount of blood glycogen, while a significant decrease was observed in the myometrial tissue. The cervical tissue glycogen levels of patients with myoma or endometriosis were significantly higher and did not exhibit cyclic or menopausal changes. There were no significant cyclic differences in the amount of endometrial tissue glycogen in women with myoma or endometriosis. In these cases the glycogen content was significantly higher than in healthy endometrial tissue. Blood glucose and plasma insulin levels were found to be in a normal spectrum. Pathological glucose tolerance and parity status showed no correlation to the variation of uterine tissue glycogen.


[Palmitic acid in amniotic fluid and its relation with gestational age and neonatal R.D.S. (author's transl)]. 503 samplings of palmitic acid in amniotic fluid are correlated with gestational age during labor or not. In nine cases of R.D.S. determinations during labor were of very low values, but not in those before labor started. Results are discussed, indicating that values over 2 mg./100 ml. show adequate pulmonary maturity. Inferior values would only be valuable if samples are obtained during labor.


[Physiopathology of idiopathic respiratory distress syndrome (author's transl)]. Physiopathology of idiopathic respiratory distress syndrome is reviewed and bases for a correct management are given. Special mention is made of pulmonary surfactant system, biosynthesis of surfoactive material and techniques used to predict appearance of pulmonary maturity.


The influence of progesterone on the antidiuretic and oxytocic activities of the posterior pituitary lobe of female rats. Mature, female rats received 2 mg progesterone i.m. during proestrus and estrus and 4 mg during all stages of the sexual cycle. 24 h after injection the animals were decapitated. Antidiuretic and oxytocic activities of the posterior pituitary lobe were tested by bioassay. The increased hormone content of the neurohypophysis in reaction to progesterone administration is explained by an inhibiting effect of progesterone on hormone secretion. The physiological and possible pathophysiological importance of this effect is discussed, expecially with regard to the genesis of cyclic edema and late pregnancy gestosis.


[Obliterative angiopathy of placental stem villi (author's transl)]. Out of 136 placentas with vascular obliterations, 25 cases were placentas of children born alive, in 92 cases the placentas belonged to children born dead. In 19 cases we had no data on the baby. In placentas of babies born alive, the same vascular changes (subtotal and total obliterations, septal partitions of vascular lumina) were found as in those of dead-born children, although considerably less severe. Vascular obliterations should not be considered as post-mortal alterations of the placenta blood vessels, since only quantitative differences could be proved. Septum-like partitions are hardly ever found in placentas of babies born alive, in dead-born babies they are more frequent. They seem to present recanalizations, and are understood as a compensation mechanism for a placental insufficiency caused by vascular obliterations. The accentuated collagenization of the placental periphery, noticed in placentas of babies born alive, is being interpreted as the consequence of an impaired blood circulation, caused by partial and total vascular obliterations. The high collagen rate in the placental periphery in placentas of the dead-born is probably a reaction to the diminished fetal circulation. Endangitis obliterations in 73 placentas out of 4600 pregnancies of cases with late abortions, premature deliveries, perinatal death, underweigh and small for gestational age babies, impaired adaptation in newborns of mothers with proteinuria and hypertension speak strongly for assuming that endangitis obliterans presents a form of placental insufficiency. Endangitis obliterans of the placental blood-vessels has, however, been discovered frequently after Rubella infection in early pregnancy. The etiological factors of the endovascular process can be multiple, the morphological and the pathophysiological reactions are the same.


Ultrasonic diagnosis of placenta membranacea. In this paper the first known case is presented in which an antepartum diagnosis of placenta membranacea was made by ultrasound. A multiparous woman is presented with intermittent painless vaginal bleeding in the second trimester of pregnancy. Ultrasonic examination at 20 weeks' gestation revealed a gestational sac almost completely covered with placental tissue. At 26 weeks the patient delivered a dead, growth retarded and an almost complete placenta membranacea.


The influence of the prolactin inhibitor bromocriptin (CB 154) on human luteal function in vivo. Five volunteers with normal ovarian cycles received oral doses of 2 X 2.5 mg or 3 X 2.5 mg bromocriptin (CB 154)/day respectively. The treatment started at the onset of menstruation and lasted on complete cycle. In addition to the decrease of prolactin secretion, a reduction of plasma progesterone concentrations during the corpus luteum phase was demonstrated. This fall of progesterone seemed to be preferentially due to bromocriptin-induced hypoprolactinaemia and not to direct ovarian effects of the drug.


Comparison between serum estriol and urinary estrogens as indices of fetoplacental function. In order to compare the predictive efficacies of serum estriol and urinary estrogen excretion in early diagnosis of fetal distress, 255 patients with normal (N = 128) or complicated (N = 127) pregnancies were monitored with simultaneous determinations of serum estriol (radioimmunoassay) and urinary estrogen excretion/24 h (colorimetric method) after the 32nd week of pregnancy. There was no difference in the efficacies of these tests. Out of all 43 fetal distress cases, 40% were predicted by serum estriol and 33% urinary estrogens. In pre-eclampsia, the respective findings were 56% and 50%. Fetal distress was the most probable (88%) when both of the tests were low at the same time. In pregnancies complicated with diabetes or rhesus immunization both tests revealed normal findings apart from the presence of fetoplacental dysfunction. The choice between these tests must be based on other factors than the diagnostic accuracy.


[Functional aspects of placental maturation in twin-pregnancies (author's transl)]. Multiple pregnancy placentas are especially efficient for examining the influence of placental maturity on fetal growth; extraplacental factors can be considered the same, and difference concerning the state of the child can be correlated with the conditions of the placental function. In 46 twin-couples placentas have been examined. In 21 cases placental parts varied in maturity. Children whose placentas had reached a better stage of maturity, were better in weight, length and Apgar score. Only in 3 cases with ripe placenta Apgar score was low (all cases were second-born children). In 25 twin-couples placentas of equal maturity were found, and the children showed insignificant differences. Differences concerning the Apgar score, could be caused by extraplacental etiological factors. 68 placental parts were correlated to the gestational age; a precocious placenta maturity was found in 31 cases, and a mature placenta in 26 cases. The importance of precocious placental maturity and its influence on the development and condition of the child post partum are being thoroughly discussed.


[The early stromal invasion of the vulva (author's transl)]. Fourty one vulvectomy operation specimens and seventeen biopsies from the vulva were examined. They represented either dysplasias, carcinomata in situ or invasive squamous cell carcinoma. Slightly more than a third of the cases showed early stromal invasion as well in dysplasias and carcinomata in situ as in the margins of the invasive carcinomas. On the other hand the early stromal invasion of the vulva doesn't show that striking alterations as does that of the cervix uteri.


[The effect of 2,4-dinitrophenol, monoiodine acetate, sodium fluoride and hypoxia on the formation of plasma polyps in the placenta of guinea pigs (author's transl)]. Plasma polyps can be found at the end of a normal pregnancy. Following NaF and MJA-intoxication, there is an extreme increase of plasma polyps. This accelerated formation can be prevented by the injection of Na-pyruvate and often the number of polyps can be reduced below the norm. 2,4-Dinitrophenol intoxication and breathing of hypoxic gas mixture (2,5% O2, 5% CO2, 92,5% N2) do not lead to increased plasma polyp formation. This proves, that it is not hypoxia, not an energy deficit secondary to separation of oxydative phosphorylation and not cardiac insufficiency leading to secondary ischemia which are responsible for the extreme increase in the number of plasma polyps following the injection of MJA and NaF.


[The abdominal fetal EKG for the analysis of pre- and subpartual heart frequency (author's transl)]. The application possibilities of abdominal fetal electrocardiography for pre- and subpartual continuous registration of the fetal heart frequency are examined. For this purpose the technical quality of 403 abdominal FEKG-registrations were checked in the individual stages of pregnancy and during birth. The average time spent looking for the best position with the greatest R-wave amplitude amounting to 2.6 min. The abdominal longitudinal position and the right hand oblique abdominal position proved to be advantageous with longitudinal presentation of the fetus. With fetal oblique to transverse presentation and in the 6th to 7th month of pregnancy the transverse abdominal position was likewise favourable. The technical quality of the supervision varied in the individual months of pregnancy. The best results were achieved in the 6th and 11th month of pregnancy. The worst technical quality was registered in the 8th month. In the 7th and 9th month two thirds of registrations were at least adequate. Sub partu the registrations during the first stage of labour were in two thirds of the cases very good and good, in a quarter satisfactory, in approx. a sixth adequate and fairly bad. In the second stage the registrations were considerably worse, 10.7% were satisfactory, 28.6% adequate and 59.8% deficient. Prepartually the technical quality was dependent on the fetal R-wave amplitude. In the second stage of labour no correlation between fetal R-wave amplitude and technical quality could be ascertained. The rupture of the amnion only influenced the quality of the registrations, if the satisfactory of labour increased. Adiposis and the position of the placenta did not affect the technical quality of the registrations. The lateral positions of the patient led to unusable registrations in 26.2%, in 46.9% the left and in 44.6% the right lateral position could be accepted without loss of quality. The comparison of the subpartual parallel registrations by means of phonocardiography/abdominal fetal electrocardiography, as well as direct/abdominal fetal electrocardiography showed no differences in the baseline. Differences in the floating-line in the case of simultaneous phonocardiography/abdominal fetal electrocardiography concerned the phonocardiographic registrations and in the case of simultaneous abdominal/direct fetal electrocardiography the abdominal registrations. They were caused by reduction in the technical quality. The fluctuation types of the abdominal and direct registrations were identical. In the case of simultaneous phonocardiography/abdominal fetal electrocardiography differences were found both in the oscillation amplitude and the oscillation frequency. The difference in the oscillation frequency was caused by a bad technical quality. The lower oscillation amplitude in abdominal fetal EKG-registrations was defined by the more exactly signal of the fetal R-wave...


Massive feto-maternal transfusion during external cephalic version, with fatal outcome. A primipara with breech presentation underwent external cephalic version under tocolysis 9 days before term. The placenta was located on the anterior uterine wall. During the version, a massive feto-maternal transfusion occurred and the baby ultimately died.


Angiotoxicity and arteriosclerosis due to contaminants of USP-grade cholesterol. Impurities were concentrated from several lots of cholesterol by recrystallizing cholesterol from methanol solution, retaining the mother liquor, and evaporating the residuum to dryness under vacuum. This concentrate contained the products of spontaneous oxidation of cholesterol and other contaminants from the original source. The concentrate increased the frequency of dead aortic smooth muscle cells and induced focal intimal edema in the rabbit 24 hours after gavage at 250 mg/kg. New or old cholesterol was similarly angiotoxic, the old more so than the new. Cholesterol purified via dibromination induced an increase in aggregate debris in 24 hours at 250 mg/kg but no increase in degenerated cells. The concentrate administered at a total dose of 1 gm/kg/seven weeks induced intimal, fibrous lesions without foam cells or hypercholesterolemia. Purified cholesterol at the same dose produced no effect.


[The experimental examination of the effect on the uterine blood flow of angiotensin II during pregnancy (author's transl)]. In experiments with animals it was investigated the endurance of the myometrial and the blood flow of the renal cortex during endogenous pressure substances. At the same time it was tested, if treatment with sexual hormones or a pregnancy had the tested principles and changes through pressure substances, and that the changes were significant. The investigations were conducted on three groups of female rabbits. The blood changes in myometrial and in the uterine were measured and continually registered with the special heated thermistor, from the principle of the thermoclearance. The success of the blood pressure was intraarterial measured with an electric mechanism. Precisely the same doses (in relativity of the animals weight) of pressure substances were applied with an infusions pump intravenously. And pressure substances Angiotensin II, Norepinephrine and Epinephrine, and their actions on the blood pressure and blood flow through the myometrium and through the renal cortex were examined. Altogether 131 values were registered. The results of the study that were statistically secure were as follows: a) The uterine blood flow pro tissue volume unit stays constant also by pregnancy or pseudopregnancy. b) The blood flow of the kidney is perhaps twice as high as the myometrial. c) The myometrial blood flow is with the arterial systolic blood pressure tightly correlated. Blood pressure increases through Angiotensin-infusion and also recovery of the uterine blood flow. d) An autoregulation of the uterine blood flow is not observed. e) The decrease of the renal blood flow after the giving of pressure substances was not modified through pregnancy. f) In quality the behaviour of the organ blood flow is the same after applied infusion of the pressure substances. Quantity differences exist however between Angiotensin II, Norepinephrine and Epinephrine. The method of measuring the blood flow through the uterus and in the kidney was placed in one view there. The finding of another examination groups for the problem of the organ blood flow in pregnancy was under critical consideration the methods combined and in connection with the proper examinations discussed. Till now in the theory over the cause of EPH-syndrom the predominate recently compiled comprehensive summary was; the proper body pressure substances--especially from the renin Angiotensin system--after chronical invoices it was decides diminished uterus blood flow appeared. After the earlier results were not all secure. The proper examination speech was therefore, that regarding the kidney function relevant alterations, also unter the conditions of pregnancy, are to be observed. The pressure dependant regulation of myometrial blood flow without proving autoregulation required however another test of the predominante gestose theory.


Coronary arterial fistula.

Coronary arterial fistula. We report two cases of coronary arterial fistula communicating with the right ventricle. It was noted that the coronary arteries did not spring from the aorta in the normal way. Proximal connections between the coronary arteries and the aorta absent. The lesions were associated with pulmonary valvular atresia, tricuspid valvular stenosis, and intact ventricular septum. We describe the clinical and autopsy findings and discuss the possible pathogenesis.


Cellular proliferation in vasa rectae in acute tubular necrosis. A histochemical and electron microscopical study. The vasa rectae of the renal cortico-medullary junction were studied in cases of acute tubular necrosis. Although routine light microscopical observations suggested a heterogeneous population of hematopoietic cells, further studies revealed two groups that showed (1) a major fraction, consisting of the lymphoplasma-cytic series with varying stages of maturation, and (2) a minor fraction of granulocytic precursors. The possible importance of this phenomenon is discussed.


Erythropoietic protoporphyria. A light, electron, and polarization microscopical study of the liver in three patients. Two of three patients with erythropoietic protoporphyria showed pigment deposits with typical red porphyrin fluorescence on liver biopsy specimens. Birefringence of this pigment by polarized light is due to its crystalline nature, as demonstrated by electron microscopy. There was slight portal inflammation in these cases. A liver biopsy specimen from a third patient was normal.


Tissue destruction in chronic pneumonitis. A hitherto unrecognized, but apparently common, feature of chronic pneumonitis is tissue destruction. This feature may be as important as the proliferative component in formation of honeycomb lung. Fifty-two selected cases of active chronic pneumonitis were studied with hematoxylin-eosin stain, followed by bleach and Gordon and Sweets silver stain for reticulin. Thus, exactly the same cells and tissue could be studied with both stains. Pulmonary tissue destruction in regions of active chronic pneumonitis was indicated by (1) the presence of structureless eosinophilic material containing karyolytic nuclear remnants, (2) the presence of fragments of degenerated reticulin fibers within the air spaces, and (3) the phagocytosis of reticulin fiber fragments by macrophages.


Intracellular mucin production by lobular breast carcinoma cells. Slides from ten cases of infiltrating lobular and ten of in situ lobular breast cancer were studied with mucicarmine stain to determine the incidence of intracellular mucin in such cases. Nine of the ten infiltrating carcinomas and six of the ten in situ tumors contained such cells. None of the cases contained infiltrating duct or "colloid" carcinoma and none had in situ carcinoma of major ducts.


[Mycotic aneurysm of extravascular origin]. The case of a female patient presenting a complete unilateral ophthalmoplegia secundaru to a septic aneurysm of the internal carotid artery is reported. The possible existence of an extravascular infectious etiology in vies of the presence of trombophelebitis of the cavernous sinus is discussed. Pertinent reports from the literature are reviewed and the rarity of the phenomenn is commented. The indication for internal carotid artery ligation as a form of treatment deserves further observations.


[Formation of the inner ear lymphs. Permeability of inner ear membranes (author's transl)]. 1. The endolymphatic system is morphologically a close system. The inner surface of the wall is tightly lined with an epithelium of ectodermal origin. The perilymphatic spaces are enlarged intercellular spaces which are built from the embryonic mesenchyme. 2. The perilymph ist an ultrafiltrate of plasma. There is probably a flow from the cerebrospinal fluid which is constantly renewed. The diffusion in the perilymph is dependent on the concentration and the size of the molecules. The endolymph is mainly a perilymph-filtrate. The "secretory" epithelia (e.g. stria vascularis cells and other tissues) of the endolymphatic system perform an important role to sustain the potassium and sodium concentrations. The ionic concentrations regulate the water movement also the volume of the endolymphatic spaces. They are maintained by anoxy-sensitive pumps. 3. The DC potential within the endolymphatic spaces represents the movement of certain electrical charge through membranes. By applying various inhibitors it is possible to distinguish the pumping mechanisms, and to observe the continuous changes of potassium and sodium concentrations with Na+ specific electrodes and K+ specific electrodes. There are probably three interdependent sources of driving-forces: a. A positively electrogenic K+-pump which is anoxia-sensitive and can be inhibited by Ethacrynic acid. This mechanism is more active in stria cells and less so in utricle and saccule. b. A negatively electrogenic Na+-K+ exchange-pump in all parts of the endolymphatic spaces is inhibited by Ouabain or anoxia. c. The passive diffusion of potassium-ions from endolymph to perilymph results an electro-negative effect.


Aspects on endolymphatic sac morphology and function. Morphological evidence indicate that the main function of the endolymphatic sac is to act as a reabsorptive and defensive mechanism for the inner ear. This activity is markedly enhanced in labyrinthine trauma, such as injection of foreign particles into the labyrinth, blocking of the endolymphatic duct, and cryosurgical destruction of vestibular sensory epithelia. Light and dark epithelial cells of the intermediate portion of the sac are capable of reabsorbing endolymph and digesting cellular debris respectively. The extensive capillary network surrounding the endolymphatic sac exhibits endothelial characteristics suggestive of active fluid transport. The "dynamic-flow theory" of endolymph circulation suggests that a radial-flow should be considered for energy metabolism and ion exchange around the sensory cell regions whereas a longitudinal-flow should be considered for reabsorption of endolymph and disposal of high molecular waist products and debris by the endolymphatic sac. The earlier concepts of endolymph circulation thus need not any longer be considered conflicting.


Microcirculation in the labyrinth.

Microcirculation in the labyrinth. The inner ear is unique in the number and variety of specialized microvascular networks that furnish blood to its parts. Four distinct capillary networks arranged in parallel supply the structures of the outer wall, and four others those of the spiral lamina. Most of the capillaries are surrounded by pericapillary spaces favoring filtration and reabsorption of fluid. In the guinea pig those of the spiral prominence and outer sulcus show a special pericapillary tissue. The strial capillaries are larger in diameter and are closely invested by strial cells. The blood within them has a higher hematocrit and flows more slowly than elsewhere in the labyrinth. The arcades of the tympanic lip and basilar membrane receive occasional innervation by fine unmyelinated nerve fibers. A possible role of prostaglandins in controlling the tone of the cochlear microvasculature is suggested. Although it appears unlikely that vascular lesions within the labyrinth could be responsible for the hydrops of Menière's syndrome, devascularization and atrophy of the endolymphatic sac might be contributory factors.


Experimental pathogenesis of hydrops.

Experimental pathogenesis of hydrops. 1. The best method for inducing hydrops in guinea pigs is obliteration of the endolymphatic duct. 2. The location of hydrops produced in the guinea pig is comparable to that of Menière's disease. 3. The major histopathological finding in the guinea pig is atrophy of sensorineural elements in the apical turns of the cochlea. 4. The vestibular sensory cell population is rarely decreased, though ultrastructural changes are noted. 5. Attempts to prevent or minimize development of hydrops by surgical fistulization of the vestibular endolymphatic walls or by administration of a diuretic drug, ethacrynic acid, failed in the guinea pig. Treatment of Menière's disease by these means is questionable. 6. Electron microscopy of the organ of Corti in cochleas taken from a patient with bilateral Menière's disease revealed that only a small percentage of te sensorineural elements was abnormal at the apical turns. Thus, it is questionable whether these small ultrastructural changes in the organ of Corti are a major cause of severe hearing loss. 7. In Menière's disease biochemical changes in cochlear fluid and/or changes in motion mechanics of the cochlear duct are probably important factors producing the hearing loss. 8. The present ultrastructural study did not resolve the question of the etiology of Menière's disease.


[Pathology of the endolymphatic duct and sac in inner-ear hydrops]. The morphological substrate of Menière's disease is the endolymphatic hydrops. That can be idiopathic or secondary as a sequence of a labyrinthine disease of another cause. It is possible to coordinate function loss of the sensory end-organs and pathohistological findings, but not all failures are light-microscopically explainable. The reason for the hydrops is certainly a disturbance in the endolymph physiology. For the pathogenesis are important, besides the biochemistry of the inner ear-fluids, problems of the membranes and pathological changes on ductus and saccus endolymphaticus and perimacular areals and plana semilunata. The perilymphatic space, documentated on the example of the secondary hydrops, is certainly not only passively enrolled in the procedure. All observations bring the initiation and periodicity of attacks to another point of view. A complete solution has not been possible so far, especially in the case of the etiology in idiopathic hydrops.


Diagnosis of Menière's disease.

Diagnosis of Menière's disease. Stapedius-reflex measurement and the glycerol-test in combination with pure tone audiogram and speech-audiogram are reliable methods for an exact diagnosis of Menière's disease. For differential diagnosis one should know the so called "tensor tympani syndrome" which is discussed in this paper.


Electrocochleographic diagnosis.

Electrocochleographic diagnosis. The most characteristic electrocochleografic features of Menière's disease are a broad waveform, steep input-output curves, normal amplitude-latency relations and large summating potentials. The electrocochleografic data obtained in an individual case can be compared with the parameters of a reference set composed of a great number of patients with a well established diagnosis. For a new diagnostic case this leads with the aid of statistical methods and computer assistance to a probability diagnosis.


Vestibular diagnosis in Menière's disease. Vestibular diagnosis of Menière's disease must be based on the results of an elaborate test battery. The latter should include a complete caloric test (stimulation with cold and warm water), carried out under nystagmographic control. Statistical analysis of caloric responses recorded in 100 normal test subjects by D.C. nystagmography show clearly that culmination frequency and culmination eye velocity are the most reliable parameters indicating an unilateral loss of function. With respect to the differential diagnosis - endorgan or neuronal lesion - only the galvanic test allows an unequivocal localisation of the site of the lesion. An analysis of 50 cases of Menière's disease reveals normal liminal and supraliminal galvanic responses without exception, thus indicating that the concomitant reduced caloric response is due to a lesion strictly confined to the vestibular endorgan. Hence the galvanic test may serve the same diagnostic purposes as supraliminal tests in pure tone audiometry.


[Differential diagnosis of dizziness (author's transl)]. The common denominator of the different meanings of dizziness is a disturbance of spatio-postural orientation, which indicates an imminent danger of fall. Höhenschwindel (fear of hights) with grasping and holding in the primate is instinctive behavior caused by a visual cliff or sudden dizziness. Because of the many possible meanings of dizziness, the case history is important for differential diagnosis. Vertiginous and non-vertiginous dizziness, black out and unsteady gait without vertigo should be distinguished. In addition, the duration and time course of the attack, releasing mechanisms and accompanying symptoms of dizziness should be explored. In recurrent dizziness without hearing loss, vestibular, vascular, cardial and epileptic disorders should be considered as well as intoxication, cerebral tumor, cerebellar hemangioblastoma, multiple sclerosis, neurosis and psychosis. Epileptic dizziness occurs not only in the prodromal stage of grand mal attacks and in temporal lobe epilepsy, but also in petit mal absences of short duration (less than 5 s) in which the blurring of consciousness is not apparent; absences of short duration are easily overlooked in childhood. Besides the objective history obtained from the patient's relatives, EEG-recording when falling asleep in the morning after one night of sleep deprivation are the best means for the diagnosis of epilepsia. Spontaneous nystagmus after complete exclusion of visual fixation is a physiological phenomenon. For differential diagnosis between physiological and pathological spontaneous nystagmus, Frenzel's spectacles in the dark room are indispensable. The distinction of spontaneous nystagmus in the narrower sense, gaze nystagmus and fixation nystagmus is discussed. The diagnostic importance of the direction of nystagmus is mentioned. Jerking nystagmus may be congenital. Pendular nystagmus may be acquired. Therefore, additional criteria for the differential diagnosis between congenital and acquired nystagmus are necessary.


[Menière's disease and sudden deafness (author's transl)]. The question is, is there any relation between sudden deafness and Menière's disease? Total hearing loss without recovery is typical of viral infection. In cases of sudden deafness some hearing rest generally remains. It can be the first symptom of Menière's disease, like the first attacks of vertigo which may occur without deafness. Measurements of stapedius reflex threshold and Békésy audiogram, especially the difference between the impulse tone and continuous tone indicate an inner hair cell damage and are helpful in the diagnosis of sudden deafness. But pathological adaptations are seen in cases of sudden deafness and also in Menière's disease. A decrease in the distance between the hearing threshold and the reflex threshold is a further indication of inner ear damage. The independence of the stapedius reflex threshold up to a hearing loss of 60 dB seems to be an indication for the different function of both types of hair cells. the reflex is supposed to be dependent only on the presence of the inner hair cells because the reflex threshold increases as soon as an inner hair cell damage of about 60 dB occurs. Clinical and audiological findings reveal no differences in sudden deafness and Menière's disease.


[Morbus Menière and acousticus-neurinoma (author's transl)]. It is questionable whether a hydrops endolymphaticus can develop on the basis of an acousticus-neurinoma. Histological evidence is also lacking. The fact that an acousticus-neurinoma can very rarely lead to the classical symptoms of Menière's disease has practical consequences. If a significant decrease in caloric function and an asymmetry in the inner ear ducts exist, a meato-cisternography is indicated. In the meato-cisternogramme typical filling defects are found; but also in 50% of the patients with Menière's disease, certain types of filling defects are seen. This observation suggests that perhaps other pathological processes in the inner ear duct provoke symptoms similar to those of Menière's disease. In our patient material we have indications that isolated intrameatal liquor circulation disturbances and intrameatal angioma are much more often associated with the clinical symptoms of Meniere's disease than an acousticus neurinoma.


[Morbus Menière and cervical symptoms (author's transl)]. The history of the patient is very important. In cervical syndroms typical pain in neck, shoulder and arm are present, often combined with occipital headache and paraesthesias. The symptoms are more pronounced during the night, while waking-up and after sudden head movements. Radiological changes mainly occur at C 4-C 7, but are not pathegnomonic. Hearing loss is rather frequent, usually one-sided and non fluctuating. The audiogram is not characteristic for its cervical origin. In 80% recruitment is present, tinnitus occurs in 30--60% of the patients, but displacusis and fullness of the ear do not occur. The vestibular symptomatology is the best differential diagnostic tool.


[Medical treatment in Menière's disease (author's transl)]. They are different methods of medical treatment in Menière's disease. 1. The dehydration of the hydrops by diet, diuretics, hypertonic solutions and glycerol. 2. Improvement of the blood supply by carbon dioxide, by myotropic and neurotropic vasodilators or by decreasing the blood viscosity and by medical or surgical paralysis of the sympathetic nerve. The optimistic results seen by acupuncture or neural therapy are not confirmed. - Experimental and double blind studies with betahistin (vasomotal) showed a significant effect in improving the blood circulation of the inner ear and the symptoms of Menière's disease. 3. Sedatives especially neuroleptics and tranquilizers were successful only by suppressing the symptoms, but are not a causal treatment. The same mechanism is supposed for procain and lidocain. 4. Partial destruction of the inner ear has been produced by local application of anesthetics or ototoxic antibiotics. These methods succeed in relieving vertigo and save the hearing in most cases.


[Surgical treatment of morbus Menière (author's transl)]. Surgical treatment is only indicated if the medical treatment is not successful. From 409 patients an operation was only necessary in 90 cases. Only those operations for which there is a long period of experience were mentioned. The early stage of the disease with a fluctuating hearing loss is reversible. It is the stage in which saccotomy with myo-synangiosis is indicated. A follow-up study of about 5 years ago showed that vertigo disappeared in 48% of cases. The hearing remained unchanged in 48% and decreased in 52% of cases. The tinnitus was completely relieved in 8% and the fullness of the ear in 56%. One patient had a total hearing loss after the operation. The different techniques of saccus operations, including the endolymphatic shunts, had all the same results and seemed therefore not to be specific. In the late stage of the disease the neurectomy of the vestibular nerve by transtemporal approach is most successful, especially when it is combined with an excision of Scarpa's ganglion. A 5 year follow-up study of 52 cases showed that 94% were without vertigo. Hearing was improved in 16% and unchanged in 64%. The tinnitus was gone in 33% and the fullness of the ear in 47%. Complications were hearing loss in 4%, a transitory facial paralysis in 3% and an incomplete compensation of vestibular function in 20%. Compared with the labrinthectomy the translabyrinthine neurectomy is an advantage. The results are similar to those of the vestibular neurectomy with the exception of total hearing loss, but the translabyrinthine approach, or cochleo-vestibular neurectomy is only indicated in cases of complete deafness.


Endolymphatic hydrops: mechanical causes of hearing loss. An explanation for the mechanical origin of the hearing loss in endolymphatic hydrops is presented that is based on studies in mechanical cochlear models. An elastic bias of the basilar membrane and/or a mass loading of the cochlear duct account for the low-frequency hearing loss, diplacusis, and even-harmonic distortion. In addition, the static shearing displacement between the tectorial membrane and the organ of Corti, caused by the displacement of the basilar membrane, may partially decouple the hair cells from the tectorial membrane, an event that would explain the tinnitus, recruitment, and perhaps even the disportional loss of speech intelligibility associated with endolymphatic hydrops.


Fish meal supplementation of chick starting rations containing cottonseed cake. Between the second and the fifth week chicks were fed starting rations on the basis of corn/wheat with cottonseed cake up to 30% as sole plant protein and with 5 to 15% fish meal and 5 to 15% cottonseed cake supplemented at a ratio of 1:1. The crude protein levels tested in this way ranged between 11.7% (corn/wheat only) and 26.7% (15% fish feal, 15% cottonseed cake). The content of ME ranged between 2266 and 2920 kcal/kg, the total gossypol content between 0.051 and 0.307%. The most favourable results (considering increase and feed consumption) were obtained with a ration of 23.4% crude protein supplenented by 10% fish meal and 10% cottonseed cake. Higher contents of crude protein required a higher feed consumption, lower contents of crude proteins yielded less increase and higher feed consumption. Cottonseed cake additions only yielded medium increases but a high feed consumption.


Long-term tissue culture of epithelial-like cells from human skin (NCTC strain 2544). I. Measurement of viscosity. Viscosities of cell suspensions of human skin epithelium (NCTC strain 2544) were determined by a Wells-Brookfield rotation viscosimeter. A structure viscosity may be postulated by the form of the viscosity curves at different shear-rates. At a cell number of 0.5 X 10(6) cells/ml a viscosity of 1.094 centipoise (25degrees C, shear-rate 230 s-1) could be found. Since a suspension of single cells may be easily formed mechanically (mopping) the NCTC 2544 cells are useful as investigational model regarding the investigation of membrane characteristics.


Glycogen levels and peripheral mechanisms of glucose-induced spppression of feeding. Rabbits deprived of food for 0, 2, 4, 6, 8, 16, and 24 h were assessed for glucose-induced feeding suppression, refeeding after deprivation, and liver glycogen. In previous research, we hypothesized a relationship between liver glycogen and the transition from duodenal to hepatic glucose suppression. In duodenally cannulated rabbits, the infusion of 10 ml of isotonic glucose in awake, free-feeding animals significantly suppressed food intake but did not do so in those food deprived for 2, 4, 6, 8, or 24 h. In hepatic-cannulated rabbits, similar amounts of glucose significantly suppressed food intake in 4-, 6-, 16-, and 24-h-deprived animals. Also, refeeding after deprivation increased as a function of continued deprivation until 6 or 8 h, when refeeding reached asymptote, or decreased through 24-h deprivations. In agreement with these observations, liver glycogen showed a sharp decline between 4, 6, and 8 h of deprivation (depending on circadian cycle). It is proposed that liver glycogen depletion, or some correlate, alters liver glucostatic regulation and determines refeeding after deprivation.


Inhibition of transmembrane K transfer in ureter-ligated dogs infused with KCl. In anuric dogs loaded with K by infusion with 2 meq KCl/kg per h until prelethal hyperkalemic cardiotoxicity appears, the extent of transmembrane K transfer depends on the origin of the anuria. Animals with bilateral ureter ligation transfer a mean of 1.2 meq/kg to intracellular fluid, while those with bilateral nephrectomy transfer more than 2.5 times as much (3.1 meq/kg). Further, if dogs with functioning kidneys are ureter ligated or nephrectomized after approximately 45 min of K loading, K transfer ultimately falls as infusion continues. The fall is precipitate and over 90% in ligated animals; but it is gradual, and only 10% in those that are nephrectomized. Finally, K transfer, because of the absence of insulin, is negligible in K-loaded pancreatectomized dogs with bilateral ureter ligation, but fairly substantial in pancreatectomized animals with bilateral nephrectomy. The data suggest that ureter ligation and hyperkalemia activate a renal mechanism that interferes with the transfer of infused K to intracellular fluid. The mechanism may involve the renin-angiotensin II-aldosterone system to a limited degree.


Washout kinetics of red cells and plasma from the spleen. Radioiodinated (125I) serum albumin was injected inttravenously in cats and allowed to equilibrate in the circulation. Red cell and plasma washout from the isolated spleens were enrom the isolated spleens were then compared during perfusion with oxygenated Ringer solution, the respective concentrations in the outflow being measured by celloscope and scintillation counters. Washout kinetics yielded three exponential components for cells (perfusate volumes for 50% washout (V1/2) being 0.067, 4.70, and 97 ml/g spleen) but only two for plasm (V1/2, 0.14 and 2.40 ml/g). There is no plasma counterpart to the slowly released cells, i.e., they do not represent a separate vascular space. This is an accord with a previous view that these are immature cells, delayed through adherence to fine structures of the red pulp. Compartment analysis indicates that the plasma and two remaining cell components represent washout from two separate vascular spaces, containing 0.09 ml/g blood at arterial hematocrit 37% and 0.42 ml/g blood at hematocrit 75%, perfused by 0.9 and 0.1 of the arterial inflow respectively. Evidence suggests these spaces are i) blood vessels, and ii) red pulp.


Relationships between resting tension and mechanical properties of papillary muscle. The influence on mechanical properties of changes in resting tension over a range from 0.5 to 4.5 g was investigated in 12 isolated cat papillary muscles. At each resting tension, the muscles contracted isometrically with the exception of an externally applied sinusoidal stretch of 0.5% Lmax (deltaL) and 20 Hz. Stiffness (deltaT/deltaL) was determined from deltaL and the peak amplitudes (deltaT) of the individual cycles from the sinusoidal component of tension. Assuming that the muscle and experimental apparatus behaved as a linear second-order mechanical system, it was possible to divide stiffness into its elastic and viscous components. During rest, total stiffness and its components were linearly related to tension. During contraction, stiffness and its elastic component were linearly related to tension. Furthermore, increasing resting tension increased the intercept and decreased the slope of this linear stiffness-tension relationship. The relationship between viscous stiffness and tension during contraction is more complex in that it is a direct relationship at low resting tensions, but an inverse one at high resting tensions.


Nephron function of the isolated perfused rat kidney. Nephron functions of an improved isolated perfused rat kidney preparation were studied by micropuncture techniques. Single-nephron glomerular filtration rate (SNGFR), intratubular pydrostatic pressures (IP), transit time (TT), and the reabsorption (R) of H2O, Na, Cl, and K were measured in superficial proximal (PT) and distal tubules (DT) of the preparation. Mean SNGFR was 27.2 nl/min and 25.2 nl/min when measured in PT and DT, respectively. The PT transport functions were well maintained throughout the perfusion (mean values were: IP, 14.3 mmHg; TT, 17.7 s; fractional (F) RH2O, 64%; absolute RH2O, 15.4 nl/min; FRNA, 66.5%; FRK, 71%, and tubular fluid-to-perfusate tf/p) ratio of Cl, 1.37). The short loops of Henle reabsorbed less than 10% of the load of H2O and Na delivered to them and the TF/P ratio of electrolytes in the earliest DT segments were high (TF/P)Na = 0.88, (TF/P)Cl = 1.27, and (TF/P)K = 1.11). This deficiency in function of Henle's loop explains, at least in part, the degree of natriuresis of the preparation (overall FRNa = 97.5%). Transit time to end DT was prolonged (82.3 S) and IP in DT elevated (14.9 mmHg). The DT was able to compensate, in part, for the overload from Henle's loop by reabsorbing 36% of the fluid load and 54% of the Na load delivery to it. We concluded that the improved isolated perfused rat kidney is a suitable preparation with which to study several aspects of renal function, particularly proximal tubules transport functions.


Sustained pressore responsiveness to prolonged hypothalamic stimulation in awake rats. Whether or not pressor responsiveness changes in unanesthetized rats during recurrent sympathetic excitation was determined by recording blood pressure and heart rate continuously while the posterior hypothalamus was stimulated repeatedly with constant currents. Because preliminary tests showed that telestimulation with a radio-controlled stimulator produced erratic responses, awake rats were routinely stimulated in a conventional manner by connecting them through wires to a square-wave stimulator. Although tachycardia was the most common chronotropic effect, bradycardia also occurred, and both responses were occasionally seen in the same rat at different times. Inhibition of chronotropic responses by combined pharmacologic blockage with propranolol and atropine did not affect corresponding pressure responses in normotensive rats. Renal and spontaneously hypertensive rats always had larger pressor responses than normotensive ones, and, in spite of individual variations, responsiveness generally remained unaltered during 3-6 h of repeated hypothalamic stimulation. These results indicate that in awake normotensive or hypertensive rats cardiovascular responses to posterior hypothalamic stimulation continue unabated even when stimulation is repeated for hours.


Glucose transport in isolated perfused proximal tubules of snake kidney. Glucose transport was studied in isolated, perfused snake (Thamnophis spp.) renal tubules. When 14C-labeled and unlabeled glucose concentrations for bath and perfusate were identical, net transepithelial glucose transport occurred from lumen to bath. Maximum rates of transport were 1.24 X 10-12 and 2.17 X 10-12 mol min-1 mm-1 in proximal-proximal and distal-proximal segments, respecitvely. Glucose concentration in cells of perfused tubules of both segments was less than that of bath and lumen when tubules spontaneously stopped transporting glucose. Transepithelial glucose permeability ath leads to lumen) was about 0.25 X 10-5 cm sec-1 for both segments. Peritubular membrane permeability (bath leads to cell) was about 0.50 X 10-5 cm sec-1 for both segments. Luminal membrane permeabilities (cell leads to lumen) were 0.29 X 10-5 and 0.65 X 10-5 cm sec-1 for proximal-proximal and distal-proximal segments, respectively. Luminal membrane permeability in opposite direction (lumen leads to cell) was about 10.0 X 10-5 cm sec-1 for both segments. These results indicate that, during maximum glucose absorption, glucose enters cells down concentration gradient across luminal membrane by a mediated process and is transported out of the cells against concentration gradient at peritubular membrane.


A role for glucose in hypothermic hamsters. Hamsters undergo hypothermia when exposed to a mixture of 80% helium and 20% oxygen at low ambient temperatures. The hypothermic hamster, rectal temperature (Tre) 7 degrees C, becomes hypoglycemic, and reversal of hypoglycemia is effected with glucose infusion. Hypothermic hamsters at Tre 7 degrees C showed a fivefold increase in survival times from 20 to 100.5 h when infused with glucose which maintained a blood level at about 45 mg/100 ml. A potential role for osmotic effects of the infusion was tested and eliminated. There was no improvement in survival of 3-O-methylglucose or dextran 40-infused animals. The fact that death eventually occurs even in the glucose-infused animal after about 4 days and that VO2 undergoes a slow decrement in that period suggests that hypothermic survival is not wholly substrate limited. Radioactive tracer, [U-14C]glucose, showed that localization of the 14C, was greatest in brain tissue and diaphragm, intermediate in heart and kidney, and lowest in skeletal muscle and liver. The significance of the label at sites important to respiration and circulation was presented.


Effect of graded doses of cortisol on total body calcium in rats. Male rats with an average body weight of 250 g were injected (sc) daily for 4 wk with 0.05, 0.20, 0.75, or 3.00 mg of cortisol acetate. Intact and adrenalectomized control animals were injected daily with 0.1 ml of vehicle (corn oil). Total body calcium (TBCa) was measured weekly in each rat by in vivo neutron activation analysis. The gain is body weight of rats treated with 0.75 mg cortisol was significantly less than controls, and the animals treated with 3.00 mg cortisol lost weight. In spite of these differences in body weight, the TBCa of all rats increased to an equal degree from an average of 1.93 g to 2.81 g in 4 wk. In addition, there were no significant differences in tibial ash calcium. However, calcium (mg) per unit length (mm) of tibia was increased in rats treated with the higher doses of cortisol; thus bone density was increased. These results demonstrate that the TBCa increases even when rats are subjected to cortisol. This is explained in part by the normal rate of intestinal calcium absorption in cortisol-treated rats.


Acid-base regulation in pregnancy.

Acid-base regulation in pregnancy. Plasma bicarbonate decreases during normal pregnancy. To assess what roles increased extra cellular volume or alterations in parathyroid hormone levels (iPTH) have in the maintenance of this decrement, we evaluated acid-base metabolism in eleven 3rd-trimester women. Base-line pH and PCO2 were 7.44 and 27.3 mmHg, respectively. Mean tubular reabsorption of phosphate was 93% and baseline iPTH levels were similar to those of nonpregnant subjects. During the slow infusion of hypertonic NaHCO3, a urinary threshold of HCO3- (THCO3) appeared at a mean plasma level of 18.9 meq/liter, but as plasma HCO3- increased progressively, its renal reclamation was almost complete and there was no evidence of either splay or tubular maximum, even when filtered loads of HCO3- reached 5 meq/min. Urine acidification was normal and distal [H+] secretory ability( deltaidification was normal and distal [H+] secretory ability (delta  urinary PCO2) was similar to that reported in nongravid subjects. In metabolic balance studies blood pH and plasma HCO3- increased (P less than .01 and less than .02, respectively) when the women changed from a high- to a low-sodium diet. Mechanisms by which decreased plasma bicarbonate levels are maintained during gestation are discussed.


Effect of hypermagnesemia on rat jejunal sodium and water transport. Hypermagnesemia decreases sodium and water reabsorption in the rat renal proximal tubule. To further understand this action, the effect of hypermagnesemia on sodium and water transport in the in vivo perfused rat jejunum was studied. The rat jejunum was chosen as another transporting epithelial tissue in the same species with unidirectional sodium flux characteristics similar to the rat renal proximal tubule, i.e., leaky as opposed to tight. Hypermagnesemia decreased net jejunal sodium and water reabsorption. This decrease was due to a reduction in unidirectional sodium efflux from lumen to blood and not to an increase in unidirectional sodium influx from blood to lumen. Hypermagnesemia did not change the jejunal permeability to inulin. The effect of hypermagnesemia on jejunal sodium and water transport is similar to that renal proximal tubule sodium and water transport. This similarity suggests that the mechanism of action of magnesium of these two transporting epithelial tissues is similar.


Hemodynamic pulmonary edema in dogs with acute and chronic lymphatic ligation. The effect of lymphatic ligation on relative lung water (g H2O/g dry lung) was studied in dogs. Raising left atrial pressure to 20 mmHg for 2 h in chronically lymphatic-ligated dogs (4 days) caused a significantly greater increase in relative lung water than the same hemodynamic challenge did in sham-operated and acutely lymphatic-ligated dogs. There was no significant difference in relative lung water between the acutely lymphatic-ligated and sham-operated dogs. At normal left atrial pressures, there was no significant difference in relative lung water between the sham-operated and chronically lymphatic-ligated dogs. Since the combined effects of chronic lymphatic ligation and left atrial hypertension is greater than the sum of the individual effects, it appears that chronic lymphatic ligation increases the susceptibility of the lung to hemodynamic edema, we suggest that chronic lymphatic ligation may have produced increases in the interstitial volume and protein mass that are undetectable by our technique. These increases, in turn, could lead to a reduction in tissue safety factors against hemodynamic pulmonary edema.


Ion transport across isolated antral mucosa of the rabbit. Isotopic fluxes of Na, Cl, and K were measured across isolated antral mucosa under short-circuit conditions. HCO3 fluxes were also measured with either isotopic and/or pH-stat methods. Net secretion of all four ions was observed. HCO3 secretion is due to a transmural process requiring metabolic energy. Secretion of endogenous HCO3 was not observed, and the unidirectional mucosal-to-serosal flux of HCO3 was negligible. There appears to be a close relationship between HCO3 secretion and the unidirectional mucosal-to-serosal Cl flux, but not relationships were observed between the unidirectional serosal-to-mucosal flux or either unidirectional Na flux. The bulk of HCO3 secretion is independent of the unidirectional Cl fluxes, but there is a fraction of HCO3 transport that is dependent on unidirectional Cl transport. However, HCO3 transport is not measurably influenced by inhibition of net Cl (and Na) transport per se.


Dietary self-selection following subdiaphragmatic vagotomy in the white rat. Nineteen female Wistar rats were employed in a self-selection-of-diet study assessing the effects of vagotomy on macronutrient consumption. Nutrients offered were a 30% sucrose solution, a 15% casein hydrolysate solution, and olive oil. In addition, noncaloric bulk, vitamins, and water were allowed. Bilaterally, subdiaphragmatically vagotomized rats showed a significant decrement in carbohydrate ingestion and daily total caloric intake (P less than .05 in both comparisons). Fat and protein intakes were unreliably altered. It is hypothesized that the vagus nerve relays glucose absorption and/or storage information from the periphery to the brain (perhaps lateral hypothalamusy, and hence, vagotomy produces carbohydrate-intake decrements, specifically. The decrement could also be explained as resulting from efferent effects of vagotomy such as decreased gut hormonal release.


Influence of oxygen and glucose on the water and ion content of swine aorta. The swelling properties of isolated swine arterial tissue have been studied to determine their effect on diffusion and hydraulic permeability measurements. Tissue potassium and sodium content were also measured to obtain an index of tissue metabolic activity. When oxygen and glucose were present in the incubation medium, a 5% decrease in tissue water content was observed over an incubation period of approximately 3.5 h. Under these conditions the tissue potassium content was higher and the sodium content was lower than when oxygen and/or glucose were omitted from the medium. When both oxygen and glucose were omitted, the potassium and sodium levels were significantly altered, suggesting a disturbance in the sodium-potassium transport system due to depletion of necessary metabolities.


Extracellular space of swine aorta measured with [14C]inulin and [14C]sucrose. Measurements of the extracellular space (ECS) of the isolated swine thoracic aorta were performed with both [14C]inulin and transient measurements and appeared to have better access to available tissue water than the [14C]sucrose gave more consistent results in available tissue water than the [14C]inulin. With [14C]sucrose as the tracer, no significant difference in the ECS was found when the tissue was incubated for 1.5 h in the presence of oxygen and glucose as compared to an incubation in which both oxygen and glucose were absent. However, the ion contents were markedly altered by this change in incubation medium. When oxygen and glucose were present tissue K+ was significantly higher and tissue Na+ was significantly lower than when these metabolites were deleted from the medium. Thus, significant alteration in ion content did not lead to substantial cell damage or bursting.


Characterization of leucine transport by toadfish liver in vivo. Kinetic analysis of L-leucine uptake by toadfish liver at 20 degrees C in vivo has been carried out after pulse injection of L-[14C]leucine into the hepatic portal vein. D-[3H]mannitol, which is taken up slowly by toadfish liver, is used as a marker for extracellular space and space accessible by simple diffusion. At normal plasma leucine concentration (0.1 mM), leucine uptake occurs rapidly (t1/2 = 0.25 min), representing a flux of 0.6 mumol/min for the liver as a whole. Analysis of the distribution of radioactive leucine among intracellular and extracellular free pools and protein-bound form at times of 30 s to 5 min after injection is consistent with operation of a concentrative or uphill transport system accounting for 40% of uptake at normal plasma concentration. Saturation of uptake occurs at increasing leucine loads; calculation of intracellular pool dilution from protein synthesis data indicates that 20-30% of liver intracellular space is occupied by incoming leucine during the first 2 min after portal injection. Maximal flux (V max) is 4.1 mumol/min per 7-g liver as a whole with Km = 0.6 mM. Competitive inhibition of leucine uptake is afforded by isoleucine and phenylalanine with lesser effects by aspartic acid, cysteine, methionine, threonine, tyrosine, and valine. No effect is observed with alanine, glycine, histidine, lysine, and proline.


Relationship of cerebral oxygen uptake to EEG frequency in isolated canine brain. Cerebral oxygen uptake was correlated with electroencephalographic (EEG) frequency and amplitude in 87 isolated canine brains. Group I (71 brains) was perfused with diluted blood and Group II (16 brains) was perfused with whole blood equilibrated with oxygen at various partial pressures. The EEG's were classified as follows: A, highest frequency greater than or equal to 17 Hz, alpha (8-13 Hz) amplitude less than 50 muv, delta (less than or equal to 3.5 Hz), amplitude less than 100 muv; B, highest frequency greater than or equal to 17 Hz, alpha amplitude greater to or equal to 50 muv, and/or delta amplitude greater than or equal to 100 muv. C, highest frequency 8-16 Hz, alpha amplitude greater than or equal to 25 muv, and delta amplitude greater than 100 muv, D, highest frequency 0.5-16 Hz, alpha, if present, amplitude less than 25 muv, and/or delta amplitude less than 100 muv, and E, highest frequency 0-16 Hz, alpha, if present, amplitude less than 10 muv, and/or delta amplitude less than 15 muv. The Group I oxygen uptakes in ml/100 g of brain per min+/-SE for the five EEG classifications were A, 4.39+/-0.06, B, 4.13+/-0.08, C, 3.76+/-0.09, D, 3.40+/-0.12, and E, 2.55+/-0.06, whereas the corresponding Group II values were A, 4.64+/-0.22, B, 4.28+/-0.15, C, 3.82+/-0.24, D, 3.39+/-0.40, and E, 1.38+/-0.42. As the EEG deteriorates, cerebral oxygen uptake tends to decrease in a significant and parallel manner in both the diluted and whole blood groups.


Independent secretion of different digestive enzymes by the pancreas. Pancreatic secretion was collected from the cannulated duct of anesthetized rabbits during the perfusion of the upper duodenum with a balanced salt solution with or without 5 mM glucose. The secretion of amylase, chymotrypsinogen, trypsinogen, and total protein was measured. While glucose did not increase overall digestive enzyme secretion, it did change the proportions of the enzymes in secretion. In addition, the following was observed: 1) non-0,0 intercepts when the output of one enzyme was plotted against that of another (an enzyme-pair plot), 2) changes in the variance of the slope and intercept of enzyme-pair plots, and 3) an increase in the variance around the slope of an enzyme-pair plot, concurrent with a decrease in the variance around the slope of a plot for another enzyme pair that contained a common member. These observations suggest that different digestive enzymes can be secreted independently of each other.


Coronary intercapillary distance during growth: relation to PtO2 and aerobic capacity. Intercapillary distance (ICD) was measured in left ventricles of rats beating in situ. Between 40 and 400 days of age, left ventricular weight increased threefold and ICD increased from 12.5-19.5 mum. ICD could be decreased by at least 2 mum at all ages studied. The number of capillaries which must be recruited to reduce ICD by 2 mum fell from 1,200/mm2 at 40 days to 280/mm2 at 400 days. Ventricular growth did not affect the O2 sensitivity of precapillary sphincters or the uniformity of capillary spacing. Calculations indicate that under basal conditions tissue PO2 (Pto2) in subepicardium is about the same at 40 and 400 days, even though VO2 per gram, capillary density, and ICD change twofold, twofold, and 7 mum, respectively. Nevertheless, as the ventricle grows, capillary recruitment becomes progressively less effective in defending Pto2 under conditions of stress. Diminished coronary capillary compensation for stress may, in part, account for the effect of age on the maximum aerobic capacity of the whole animal.


Parallel secretion of digestive enzymes by the in vitro rabbit pancreas. Nonparallel discharge of digestive enzymes by the in vitro rabbit pancreas has been previously reported and this observation has been used to challenge the mass transport theory of enzyme synthesis and secretion by the exocrine pancreas. The current investigation reexamines the pattern of enzyme secretion from the in vitro rabbit pancreas. Secretion of alpha-amylase, trypsinogen, and chymotrypsinogen was studied from the unstimulated gland and from glands stimulated with either methacholine, cholecystokinin-pancreozymin, or the active octapeptide of cholecystokinin-pancreozymin. In all cases, only parallel discharge of alpha-amlyse, trypsinogen, and chymotrypsinogen was noted. These observations are consistent with the mass-transport theory.


Effect of glycodihydrofuisidate on sulfobromophthalein transport maximum in the hamster. The effect on sulfobromophathalein transport maximum (Tm) and biliary lipid secretion of sodium glyco-24,25-dihydrofusicate, a micelle-forming compound secreted into bile, has been studied in the hamster and compared to that of a physiological bile salt, sodium taurocholate. Biliary phospholipid and cholesterol secretion increased both during glycodihydrofusidate and taurocholate administration, an observation which suggest that both compounds increased th biliary secretion of micelle-forming compounds. In contrast, only taurocholate increased sulfobromophthalein Tm into bile, while glycodihydrofusidate administration decreased it. This observation suggests that the increase in sulfobromophthalein Tm observed during taurocholate administration is not the result of micellar sequestration. It could rather be the consequence of a specific effect of bile salts on the dye transport system.


Effects of intravenous meperidine and meperidine with promethazine on uterine activity and fetal heart rate during labor. A prospective study of the effects of the i.v. injection of 75 mg meperidine, alone or combined with 25 mg promethazine, was conducted by continuous and direct monitoring of the fetus and of intrauterine pressure. The study was carried out in 16 primiparas and 24 multiparas in active spontaneous labor with cervical dilatation of 3 to 4 cm. Administration of meperidine and of meperidine with promethazine was associated with an increase in uterine activity of 31 to 45% (Montevideo units), respectively. The most marked effects were on the amplitude of the uterine contractions. There was no significant change in uterine tone. A tetanic response was recorded in two patients who vomited after the administration of meperidine with promethazine and was followed by slowing of the fetal heart rate. In no other cases were there significant changes in fetal heart rate. Except for the latter two patients, no adverse effect of meperidine or of meperidine with promethazine on the fetal heart rate was noted. The condition of the newborns at birth was excellent in all but three cases, in two of which maternal amniotic infection and high fever were present.