Respiratory modulation of baroreceptor and chemoreceptor reflexes affecting heart rate through the sympathetic nervous system.

1. Brief stimuli were delivered to the carotid body chemoreceptors or the carotid sinus baroreceptors at different phases of the respiratory cycle in anaesthetized dogs. Chemoreceptor stimulation was achieved by injecting small volumes (0.2-0.5 ml.) of warmed saline equilibrated with CO(2) near to the carotid bodies on both sides. Baroreceptor stimulation was achieved by injecting larger volumes (2-5 ml.) of saline equilibrated with air into the region of the carotid bifurcation on both sides, after first clamping the common carotid arteries.2. When the vagus nerves were intact, but sympathetic nervous effects on heart rate were blocked by administration of propranolol, there was a prompt and pronounced bradycardia evoked when either baroreceptor or chemoreceptor stimuli were given in expiration, but little or no change in heart rate when they were given in inspiration.3. When the vagus nerves were cut, but sympathetic nervous function was intact, respiratory modulation of both baroreceptor and chemoreceptor reflex effects on heart rate could still be demonstrated. The bradycardia evoked by either stimulus was more marked for stimuli given in expiration than for stimuli given in inspiration. A complementary response pattern for brief decreases in baroreceptor stimulation (carotid occlusions) was demonstrated: the tachycardia evoked by occlusions timed during inspiration was greater than that evoked by occlusions timed during expiration. All the reflex effects were mediated by the sympathetic system because they were abolished by administration of propranolol.4. Typically, the sympathetic reflex effects were slight in comparison with the vagal reflexes evoked by either chemoreceptor or baroreceptor stimuli.


Reflexes in cat ankle muscles after landing from falls.

1. Electrical activity and length of ankle muscles were recorded by telemetry during free fall and landing in cats. 2. After foot contact, there was a delay in onset of stretch of ankle extensors of between 8 and 11 ms. High-speed cinematography showed the delay to be associated with rapid initial dorsiflexion of the toes. 3. Electromyograms (e.m.g.) from lateral gastrocnemius increased in amplitude prior to landing. An early depression of lateral gastrocnemius e.m.g. commenced at 8 ms after foot contact, and was followed by a large peak of activity commencing some 8 ms after the first increase in lateral gastrocnemius length. 4. Local anaesthesia of the plantar cushion did not alter this pattern of response. 5. The early inhibition of lateral gastrocnemius was attributed to the action on lateral gastrocnemius motoneurones of non-cutaneous afferents responding to the initial toe dorsiflexion. Additional autogenetic inhibition may also have contributed. 6. The subsequent peak of e.m.g. was at a latenty consistent with a rapid stretch reflex, and occurred soon enough for the resulting active tension to contribute significantly to the extensor force during body deceleration.


Antagonism by indomethacin of neurogenic hyperthermia produced by unilateral puncture of the anterior hypothalamic/preoptic region.

1. In unanaesthetized rats, restrained at an ambient temperature of 24 degrees C, the anterior hypothalamic/preoptic (AH/PO) region was lesioned unilaterally by acute mechanical puncture.2. In control (no pre-treatment) rats, unilateral AH/PO puncture produced a neurogenic hyperthermia which began immediately, reached its peak magnitude (mean peak magnitude = +2.3 degrees C) within 60-90 min and persisted usually for 8-16 hr. At defervescence, core temperature fell to a level near that of the pre-lesioning base line.3. The prostaglandin synthesis inhibitor, indomethacin, administered I.P. at doses of 5 and 15 mg/kg 1 hr before puncture of the AH/PO region, attenuated the lesion-induced hyperthermia in a dose dependent fashion. The higher dose reduced peak magnitude by 80% and the 6 hr Fever Index by 88%. The vehicle used to dissolve the indomethacin (60% DMSO/40% saline) did not significantly attenuate the hyperthermia.4. In rats that were hyperthermic after AH/PO damage, indomethacin (10-15 mg/kg I.P.) caused core temperature to fall promptly to near the prelesion base line. Reversal occurred whether the indomethacin was injected while core temperature was still rising or late in the plateau phase of the hyperthermia.5. It is suggested that the neurogenic hyperthermia elicited by unilateral lesioning of the AH/PO region was mediated by prostaglandins released from injured tissue and possibly from extravasated blood. Evidence is cited indicating that the most likely sites of action of the released prostaglandins are the surviving portion of the AH/PO region on the punctured side and the intact contralateral AH/PO region.


The role of acetylcholine in the regulation of ion transport by rat colon mucosa.

1. Acetylcholine increases the potential difference across rat proximal colon both in vivo and in vitro.2. There is a sigmoid relationship between the change in potential difference and the logarithm of the dose of acetylcholine. The dose-response curve is shifted to the left by neostigmine and to the right by atropine, suggesting that the action of acetylcholine is mediated by a muscarinic type of receptor.3. The dose-response curve for acetylcholine in vivo is not altered by the ganglion-blocking agents hexamethonium and pentolinium, suggesting a direct effect of this transmitter on the colon.4. Acetylcholine causes an increase in potential difference, a small decrease in resistance and hence a rise in the current generated by both normal and stripped everted sacs of rat colon.5. In the absence of sodium, the calculated current change produced by acetylcholine is reduced, and the removal of chloride has a similar inhibitory effect. The absence of bicarbonate does not significantly affect the response.6. Acetylcholine virtually abolished net sodium movement and induced net chloride secretion and these changes accounted for the increased short-circuit current.7. Acetylcholine had no effect on oxygen consumption by rings of colon.8. Tracts staining for acetylcholinesterase were observed running from the submucous plexus towards the mucosal epithelium.9. This study shows that acetylcholine can influence ion movement by rat colonic mucosa and suggests that the autonomic nervous system might be involved in the regulation of transport mechanisms in this tissue.


Direct excitatory interactions between spinal motoneurones of the cat.

1. Ninety-seven spinal motoneurones were identified by their antidromic invasion following stimulation of the muscle nerve and submitted to a series of four tests to reveal a possible direct excitation between motoneurones. 2. Threshold differentiation, refractoriness, hyperpolarization and collision revealed antidromically induced depolarizations in fourteen of the ninety-seven tested motoneurones. 3. The parameters of the antidromically induced depolarizations indicate a short latency, a low amplitude and independence with regard to the membrane polarization. 4. It is concluded that the antidromically induced depolarizations reached the impaled motoneurone via a route other than its own axon. 5. The mechanism may involve either electrotonic interactions between neighbouring motoneurones or excitatory recurrent collaterals between synergist motoneurones.


Fatigue of long duration in human skeletal muscle after exercise.

1. After severe muscular contraction in man recovery of force is largely complete in a few minutes, but is not wholly so for many hours. The long-lasting element of fatigue is found to occur primarily for low frequencies of stimulation (e.g. 20/sec), and is much less pronounced, or absent, at high frequencies (80/sec). The twitch force is an unreliable measure of the state of fatigue. 2. The long-lasting element of fatigue is not due to depletion of high-energy phosphate nor is it due to failure of electrical activity as recorded from surface electrodes. It is probably the result of an impairment of the process of excitation-contraction coupling. Its practical importance for man could be significant as an explanation of the subjective feelings of weakness following exercise.


The morphology of hair follicle afferent fibre collaterals in the spinal cord of the cat.

1. The enzyme horseradish peroxidase (HRP) was injected into single axons that innervated hair follicle receptors to study the morphology of their collaterals in the dorsal horn of the cord. The axons were impaled near the dorsal root entrance zone in the lumbosacral spinal cord of anaesthetized cats and HRP injected by passing current through the intra-axonal micro-electrode. The morphology was revealed by subsequent histochemistry.2. Thirteen hair-follicle afferent fibres were stained including six that innervated tylotrichs (type T hair follicle afferent units) and one that innervated guard hairs (type G unit). The remaining six axons were not classified according to hair type, but, on the basis of their axonal conduction velocities, would have been either type G or T.3. Eleven axons could be traced back into the dorsal roots. Eight of these, upon entering the cord, turned and ran towards the brain. They did not divide into rostral and caudal branches. Three of the eleven did divide and gave rise to both rostral and caudal branches.4. Sixty-three collaterals were given off the thirteen stained axons. All well-filled collaterals had a strikingly similar morphology. They descended through laminae I-III of the dorsal horn into the deeper parts of lamina IV or into lamina V, before turning and ascending back into superficial lamina IV and lamina III where they branched profusely to give rise to their terminal arborizations. Terminal boutons, most commonly of the ;en passant' type, were numerous in lamina III, but were also seen in the dorsal part of lamina IV and in ventral lamina II. None were observed in dorsal lamina II or near the junction of the grey and white matter (lamina I) or in lamina V.5. The terminal arborizations of collaterals from a single hair follicle afferent fibre were in line with one another in the longitudinal axis of the cord. In the better-stained preparations the terminal arborizations of adjacent collaterals from a single axon formed a continuous longitudinal column through the dorsal horn. There was a gradual shift of the column of arborizations from lateral to medial as the more rostral collaterals were given off.6. The hair-follicle afferent fibre collaterals are now identified as the ;collaterales grosses et profondes de la substance de Rolando' of Ramón y Cajal (1909) which give rise to the ;flame-shaped arbors' of Scheibel & Scheibel (1968).7. The importance of the longitudinal organization of the terminal arborizations for an understanding of the topographical properties of dorsal horn neurones is discussed.


Atrial receptors in the dog and rabbit.

1. Action potentials were recorded from slips of the cervical vagi in anaesthetized dogs and rabbits. Single functional units with atrial patterns of discharge (Paintal Type A, B and intermediate) were obtained and then attempts were made to alter (i.e. convert) their patterns of discharge. Finally the points of origin of these action potentials were located.2. Thirty unselected units were investigated in thirty dogs. Twenty-seven of these were located in the endocardium of the vein-atrial system and the ratio of the type A, type B and intermediate type receptors was 1:16:10; three units were located elsewhere in the chest. Conversion of the pattern of discharge was achieved in twenty of the twenty-seven units; conversion was achieved in the single type A unit.3. In a second series of experiments in dogs, eight Paintal Type A units were selectively studied in fifteen animals. Four of these were located in the endocardium and all were converted. The remaining four were located outside the endocardium and conversion could not be achieved in two of these. Thus in the entire investigation, the ;type A' units which could not be converted were all located at sites other than the atrial endocardium.4. In the corresponding unselected study in the rabbit, eleven units were studied in eleven animals. Nine of these units were located in the atrial endocardium and the ratio of the type A, type B and intermediate type receptors was 2:1:6. Conversion was achieved in both type A units, the sole type B unit and two of the intermediate units. One of the two units found outside the atrial endocardium was a ;type A' unit and could not be converted.5. The present investigation has shown that the atrial receptors with a Paintal Type A pattern of discharge are relatively rare in both dogs and rabbits. Conversion of the pattern of discharge is a relatively common phenomenon. Evidence for the proposition that there is one basic type of atrial receptor whose pattern of discharge is determined by its precise location in the vein-atrial system is discussed.


[The role of the Scanner in traumatic cerebral pathology (author transl)].

The authors describe the tomodensitometric characteristics of various traumatic cerebral lesions: extradural haematoma, subdural haematoma, contusion. In the acute phase, traumatic lesions are characterised by the typical absorption pattern of the bloody effusion and perilesional oedema. In association with these specific densitometric signs there is naturally an alteration in normal cerebral anatomy. The course of traumatic lesions may be followed using the scanner. The signs alter with resorption of the haemorrhage and the regression of oedema, as well as with the secondary development of a focal atrophic process. The advantages of the scanner over oconventional neuroradiology are considerable, not only from a medical and technical standpoint, but also for ethical and medicolegal considerations.


[Radiological study of arthrogryphosis. 20 cases (author transl)].

Arthrogryphosis, a disease of unknown nature, is accompanied by radiological manifestations which involve essentially the limbs and spine. A distribution involving all four limbs is the most common. The commonest radiological abnormalities are equinovarus clubfoot, clubhand in ulnar deviation, scoliosis and dislocation of the hip. The radiologist examines such children in order to assess the extent of their disease and follow such orthopaedic problems as they may develop.


[Osteosclerosis in the phalanges in sarcoidosis (author's transl)].

Osteosclerosis in the phalanges is a frequent finding in sarcoidosis and its incidence appears higher then that of the osteolytic lesions. Of 19 patients with histological diagnosis of sarcoidosis areas of bone sclerosis in the phalanges were found in 6 cases (31, 5 percent).


[Radioclinical aspects of tibio-tibial diaphyseal toxo-pachyosteosis. Weismann-Netter and Stuhl disease. Two new cases (author's transl)].

The authors report two cases of individuals sufferring from bow-leggedness, which they attribute to tibio-fibular thoxo-pachyosteosis. On the basis of these new cases, they review the radioclinical characteristics of the diagnosis of Weismann-Netter and Stuhl tibio-fibular toxo-pachy-osteosis. This dysmorphic syndrome is usually familial, very likely of genetic origin, and characterised by the small stature of those affected with curving of the tibia and fibula with an anterior convexity and thickening of the posterior cortex of the bony diaphysis. This clinical and radiological individuality permits its differential diagnosis from rickets and congenital syphilis, with which it was long confused. This dysmorphy causes no problems and therefore requires no general treatment.


[Inversion of intraheptic portal flow in contusions of the liver: a new concept of traumatic arterioportal fistulas (author's transl)].

Inversion of the intrahepatic flow is a phenomenon commonly observed during the initial days of a liver contusion. Its symptomatology combines one direct sign: segmentary, peripheral arterioportal reflux; and two indirect signs: arteriolar hypervascularization and a functional amputation of portal flow on selective arteriography of the superior mesenteric artery in the same territory. The direct sign may be absent, and may not be visualized in the absence of a selective injection. Both indirect signs are always present and enable the diagnosis. In most cases it is a question of a transient phenomenon secondary to a inflammatory reaction released by the contusion of the liver parenchyma; it may be the only sign of liver trauma. It may be a sign of a benign contusion and is not alone an indication for surgery. This concerns a hemodynamic phenomenon which must be clearly differentiated from arterioportal fistulas with which it is often confused.


[Pathogenetic left tracheal bronchus. A review of the literature in connection with four cases (author's transl)].

The so-called left "tracheal" bronchus is usually found to be a transposition of the segmental apicoposterior bronchus of the upper left lobe onto the terminal portion of the main trunk. This systematisation abnormality is less common on the left than on the right. In our experience, based on 1,500 bronchographs carried out on adults and children, we have discovered seven left "tracheal" bronchi four of them associated with an obstructive emphysema in the same area. Although this malformation is rarely encountered in the etiologies of interlobular or poly-segmental emphysemas in children, it does however appear that an upper left emphysema has two etiologies which are peculiar to it: segmental bronchial atresia and left "tracheal" bronchi. Why the left "tracheal" bronchi is more often pathogenetic in comparison with the right is open to speculation. As in many other examples of tracheo-bronchial compression for vascular reasons, the close contact between the hyperarterial ectopic bronchi and the left pulmonary artery seems, logically, to be the culprit.


[Lower limb lymphography where there is no lymph circulatory disorder. Normal conditions and their limits (author's transl)].

Further lymphangiography for the lymphatic system dependent on the internal saphenous vein carried out on 70 patients to establish a lymphographical record of the pelvi-abdominal ganglia, simplified the counting of opacified vessels, and assessment of the development of the vascular system and the fragility of the walls and their calibre and pathway. The various aspects were assessed in relation to the anatomical situation (leg, thigh), age group and sex of the patients. Computerised analysis of the information lead to the conclusion that, even under normal conditions, there are statistical differences in the number of opacified vessels in the legs and in vascular fragility of the pre-inguinal region according to age group. The authors discuss the implications of the limits of the normal appearance of the lymphatic vessels.


[Lymphographic pictures in angio-immunoblastic lymphadenopathy (author's transl)].

Angio-immunoblastic lymphadenopathy, which has been recently individualized, is seen clinically as a stade III or IV haematosarcoma. Its etiopathogeny is mysterious and histological diagnosis is often difficult. Lymphography can assist diagnosis for, in an appreciable number of cases, the pictures which appear in association make it possible to distinguish between haematosarcomas occurring in Hodgkin's disease and others.


[Analysis of one thousand liver scans carried out using technetium phytate (author's transl)].

One thousand liver scans were carried out using technetium phytate. This soluble compound is transformed in the circulating blood into a colloid by chelation of serum calcium, thereby forming a macromolecular phytate of calcium and technetium. The presenting symptoms are compared with the isotopic findings. This microcolloid has the advantages common to all technetium tracers and, in addition, is easy to prepare and has the advantage of a distribution between the liver, spleen and bone of the same type as that seen with colloidal gold 198 without the dosimetric problems associated with the latter. Although it has a level of hepatic fixation which is less than that of certain sulphide complexes of technetium, the authors feel that it appears to provide a better relfection of the colloidopexic function of the liver.


[Retroperitoneal haemangiopericytoma (author's transl)].

The author's present a case of left retroperitoneal haemangiopericytoma with a malignant potential. They emphasise the value of angiography in the assessment of this rare disorder.


[A rare case of double biliary fistula (author's transl)].

The authors report a rare case of a double cholecysto-duodenal and cholecysto-colic fistula.


[Value of the Chiba needle in the technique of percutaneous transhepatic cholangiography. 20 cases. (author's transl)].

The authors used the Chiba needle for percutaneous trasphepatic cholangiography in 20 patients. Catheterisation of non-dilated biliary canals is easy with this new piece of equipment, making it possible to confirm or eliminate the presence of an obstruction. There were no severe complications. The authors report a certain number of incidents which were troublesome during the examination and in the interpretation of the results: intraparenchymatous injection, sub-capsular injection, defective filling.


[Thyroid carcinomas. Critical study about 138 observations. Therapeutic deductions (author's transl)].

Between 1952 and 1973, 138 patients with thyroïd carcinoma have been recorded. From the critical study of these cases, the pathological, etiological and clinical features have been studied. Different therapeutic modalities are evaluated from these cases. Surgery was always used when possible. A hemithyroïdectomy was realised most often. We stress that sterilisation was obtained by 131I treatment in plurifocal metastasis, particularly in pulmonary metastasis, only when the iodine uptake was sufficient. Survival has been evaluated according to the pathology: papillary and vesicular carcinomas have a good prognosis (the papillary and vesicular survival rate at 10 years reaches respectively: 65% and 64%). Anaplastic carcinomas have a bad prognosis (the survival rate at 5 years is 18%, at 10 years, 0%. These results are similar to those published by differents authors. At the opposite, trabecular carcinomas have a very short survival (8% at 5 years, 7% at 10 years) which is very unusual in well differentiated thyroïd carcinomas. It has to be isolated from the others.


[Technical record in radiotherapy (author's transl)].

The term "technical record in radiotherapy" is used to describe collected information relative to treatment using radiation. The subject of this session of the chapter of Radiotherapy of the Société Française de Radiologie was the intrinsic functions of this record and its extrinsic limitations. The extreme diversity of the current state of the record is a known fact. A majority of participants express the desire for uniformisation of the collection of data or even, as a second stage, to have a common record. A library of technical records was set up under the responsibility of the Centre Georges-François Leclerc at Dijon (J.C. Horiot). One broad conclusion was seen to emerge: the creation of a minimum common record including essential information to which could be added the more specific data of each radiotherapist and at each time of use. Prior agreement will be necessary with regard to the standardisation of apparatus and the expression of the dose. This session was of necessity merely a reflection of future needs and it is to be hoped that the good will which was obvious during the course of the discussion may produce concrete results in the months to come.


[Scanning of bone metastases (author's transl)].

The Centers against cancer of Caen, Angers, Montpellier, Strasbourg and "the Curie Foundation" have confronted their experience in detection of bone metastases by total body scanning. From the investigation by this procedure, of 1,467 patients with cancer, it results: --the confrontation between radio and scanning shows a rate of false positive and false negative identical to the literature ones; --the countage scanning allows to reduce the number of false positive; --scanning allows to direct bone biopsy and to improve efficiency of histological examination.


[Optimalization of radiotherapy of skin epitheliomas: role of the NSD].

After integration of chronological factors according to Ellis' formula and of B.R.E. for various energies of radiation, the reference dose at the deep limit of the tumor and the surface hyperdosage are kept constant. The values which have been adopted after a very large clinical experience are the following: --reference dose: 6000 rads (N.S.D. 1760). --surface dose: 8400 rads (N.S.D. 2200). The choice of the energy of radiation is the only variation, depending on the thickness of the tumor. A few schemes of equivalent chronological factors are presented, giving less than 1 p. 100 risk of recurrence and a small risk of late radiolesions for normal tissues.


[Radiological diagnosis of tumoral lipomatosis of the renal sinus. The role of arteriography (author's transl)].

In twenty cases of pseudo-tumoral sinusal lipomatosis for which the patients had undergone renal arteriography, the authors investigated the urographical and arteriographical clinical signs by comparing them with the previously published data. After reviewing these various elements and considering the various possible diagnoses, they came to the conclusion that, although the arteriographic signs are quite distinctive, they are not absolutely essential for diagnosis of this disorder--which it should be possible to confirm unreservedly from the urographical data in all cases in which there are considerable anatomical lesions. A well-managed urographical technique and careful assessment of the facts should allow arteriography to be discarded, indications for this only being justified where there is an associated symptomatology, especially haematuria.


[Contribution of arteriography to diagnosis of secondary arterio-digestive fistulas. Intestinal haemorrhage due to ilio-ileal fistula, a complication in vascular reconstruction (author's transl)].

The authors describe a case of secondary ilio-ileal fistula revealed by an intestinal haemorrhage which occurred ten years after vascular reconstruction. They stress the importance of arteriography which shows up the pseudo-aneurysm causing the fistularisation and vascular contrast material escaping into the digestive lumen. A complete review of the literature on arterio-colonic fistulas, and more particularly, ileo-ileal fistulas, shows that they usually express themselves clinically in the form of digestive haemorrhages occurring generally after vascular graft and after a variable lapse of time. The association of digestive haemorrhage and a previous vascular reconstruction should suggest the diagnosis of arterio-digestive fistula and should lead to early angiography to enable coherent surgical strategy to be put into operation.


[Lymphoid hyperplasia of the small intestine associated with primary hypogammaglobulinaemia in the adult. One case (author's transl)].

The authors present a clear radiological syndrome of lymphoid hyperplasia of the small intestine associated with hypogammaglobulinaemia in the adult, this association having first been described in 1966. This hyperplasia does not alter the course of the disease and, although not invariably present, should be familiar to radiologists as being indicative of, amongst other diagnoses, of primary hypogammaglobulinaemia of the adult.


Short-latency effect of testosterone on copulatory behaviour and ejaculation in sexually experienced intact male rats.

The effect of a single injection of testosterone on the number of stimuli required to trigger ejaculation and on copulatory behaviour was investigated in sexually experienced intact male rats. An intraperitoneal injection of 100 microgram free testosterone 1 h before testing facilitated the copulatory behaviour and decreased the number of mounts and intromissions needed for ejaculation; the latter effect was obtained in a test in which a constant interval was kept between each intromission.


Fertilization and development capability of bovine follicular oocytes matured in vitro and in vivo and transferred to the oviducts of rabbits and cows.

Follicular oocytes were cultured for 24 h in vitro or obtained 6-24 h after HCG injection from cows pretreated with PMSG, and transferred to the oviducts of oestrous rabbits or heifers, inseminated with bull spermatozoa, to determine their capability for normal development. More than 65% of oocytes cultured in fetal calf serum, equilibrated with 5% CO2 + 5%O2 + 90% N2, matured to metaphase II within 24 h. Fertilization was not obtained in the rabbit oviduct but about 8% of oocytes matured in vitro underwent parthenogenetic cleavage. Sperm penetration was observed in 49% of oocytes in the cow oviduct, but although 47% had undergone development 96 h after transfer few developed to morulae and blastocysts, confirming the impaired ability of oocytes matured in vitro, as assessed by nuclear change, to develop normally. Oocytes obtained from heifers slaughtered 24 h after HCG developed normally when transferred to the oviduct of inseminated heifers. Of the oocytes with an activated cumulus, 39% developed to blastocysts and of 16 blastocysts transferred to suitable recipients, 13 developed to normal fetuses at 13-17 weeks gestation.


Differences in the effects of vasopressin and oxytocin on rabbit myometrial activity and a possible mediation of prostaglandins.

Uterine responses to vasopressin and oxytocin were monitored in non-pregnant and 3- or 6-8-day-pregnant rabbits by recording the intrauterine pressure. Oxytocin stimulated uterine activity in all groups, but the effect of vasopressin was stimulatory in non-pregnant animals, inhibitory in those 3 days post coitum and weakly stimulatory in those later in pregnancy. Inhibition of prostaglandin (PG) synthesis, by the administration of indomethacin, reduced the spontaneous uterine activity as well as the responses to oxytocin and vasopressin in the non-pregnant rabbits, but had little effect in the pregnant animals. During infusion of PGF-2alpha, PGE-1 or PGE-2 in 6-8-day-pregnant rabbits, the stimulatory response to vasopressin, although slight before the infusion, was inhibited whereas the stimulatory response to oxytocin remained virtually unchanged. The results suggest that vasopressin and oxytocin under certain hormonal conditions, are able to activated the uterine contractions by mechanisms in which the involvement of PG is not obligatory.


Influence of genetic factors on the fertilization of mouse ova in vitro.

In-vitro fertilization was studied in F1 hybrids, 4 inbred and outbred strains of mice. Experiments were performed with intact ova (Series I) and denuded ova (Series II). In Series I the highest percentages of fertilization were obtained with gametes of F1 hybrids (86.7%) and of the CBA strain (87.5%). The KP, KE, and particularly the C57 strains, which in vivo give less than 100% fertilization, also gave low indices in vitro (42.9, 26.0 and 8.6% respectively). Testing gametes of these inbred strains with F1 gametes showed that spermatozoa and ova are responsible for the low percentages of fertilization. The rate of fertilization was mainly dependent on the genotype of the spermatozoon. In Series II, high percentages of fertilization (97-100%) were regularly obtained in all groups, indicating that differences between strains pertained mainly to binding of spermatozoa with the zona pellucida. The incidence of polyspermy, which did not exceed 5% in Series I and reached 58% in Series II, was dependent on the genotype of both gametes.


Assessment of spermicides by a stripping technique against human spermatozoa.

Fifty-two (52) compounds were tested for spermicidal activity by titration against human spermatozoa. The gradual decrease in mean sperm size was measured against increasing concentration of spermicide and the end-point was taken as the point at which all the peripheral cytoplasm had been removed and only the sperm core of nucleus and tail fibres remained. There were 14 compounds that produced this total effect. All were detergents, of various types, and the effect was purely physical. The most potent compounds caused complete stripping at 0.5-50 pmol/cell and most are already used in spermicidal preparations. A further 11 compounds, including sodium hypochlorite and some phenols, caused partial stripping, while 4 compounds caused sperm swelling. The test was not suitable for assessment of metabolic cell poisons.


Mechanism of action of oxidized polyamines on the metabolism of human spermatozoa.

Oxidized spermine, an iminoaldehyde (N,N'-bis (3-propionaldehyde) 1,4-diaminobutane), is a non-competitive inhibitor of fructolysis by human spermatozoa. The inhibition constant is about 0.3 mM. In experiments with [U-14C]fructose the iminoaldehyde caused a more pronounced depression of the formation of CO2 than of lactate. The iminoaldehyde was without influence on the conversion of fructose to lactate by cell-free extracts of spermatozoa, but it markedly decreased the uptake of fructose and lactate by spermatozoa. These findings strongly suggest that inhibition of the fructose metabolism of intact spermatozoa was due to interaction of the iminoaldehyde with sperm membranes and not to inhibition of any enzyme of the glycolytic pathway. Several aliphatic and aromatic aldehydes were also tested for their ability to inhibit sugar utilization of human spermatozoa: only n-hexanal exerted an inhibitory effect, the extent of which approached that of oxidized spermine.


Changes in myometrial and placental 15-hydroxyprostaglandin dehydrogenase with ovine parturition: production of prostaglandin metabolites in vitro and in vivo.

15-Hydroxyprostaglandin dehydrogenase (PGDH) was measured in vitro in myometrium and maternal cotyledons from 6 sheep and in fetal cotyledons from 3 sheep before and after parturition. Maternal cotyledons contained more PGDH than fetal cotyledons or myometrium. At parturition, PGDH activity decreased in myometrium but increased in fetal and maternal placental tissue. The enzymatic activity observed in vitro did not result in a large, consistent release of prostaglandin F metabolites into the utero-ovarian vein in vivo, and such activity may have a strictly localized effect in ovine parturition.


A study of peroxidase levels in human cervical mucus as an index of ovulation.

Fourteen healthy women were screened for the following parameters throughout one complete menstrual cycle: levels of urinary oestrogens and pregnanediol; levels of plasma and urinary gonadotrophins; and pH, protein content and levels of peroxidase in the cervical mucus. It was found that concentrations of peroxidase in the cervical mucus were not a reliable index of ovulation.


The distribution of events in the human menstrual cycle.

Daily reports of 85 married couples concerning their sexual behaviour for about 3 menstrual cycles per couple were organized according to menstrual events by using six techniques of aggregation. While there were some similarities among the different displays, including an apparent peak about 6 days before mid-cycle, different methods of aggregation produce widely different frequency curves. It is concluded that there is no single method of display of events of the menstrual cycle which will fit all investigations.


Studies on the equine placenta. III. Ultrastructure of the uterine glands and the overlying trophoblast.

Ultrastructural studies of the uterine glands at intervals during pregnancy in the mare show that secretory activity continues after formation of the placental exchange units. The nature of the glandular secretion appeared initially to be proteinaceous, but cellular debris was also present during the last third of gestation. These secretions were absorbed by the trophoblast overlying the mouths of the glands. The fate secretions and their significance for the fetus and placenta are unknown.


The blood-testis barrier and temperature damage to the testis of the rat.

The integrity of the blood-testis barrier was investigated during and after local heating of rat testes sufficient to produce a temporary cessation of spermatogenesis. The flow, ionic composition and protein content of rete testis fluid (RTF) collected from testes maintained at 33 or 41 degrees C were unaffected either at the time of treatment or up to 2 days later when the major cytological consequences of heating occurred. The normally low rate of transfer of albumin from blood to RTF was unaffected during and after heating. Transfer constants for radioactive K, Rb, Na and lysine consistently increased during heating although there were time-dependent differences between the patterns of response for each molecule. The normally rapid transfer of testosterone was unaffected by heating, but the entry rates of radioactivity into RTF after the infusion of more slowly diffusing steroids were enhanced at 41 degrees C. The clearest effects of heating were an approximate doubling in the uptake of oxygen and decrease in the net synthesis of protein by the testis. It is concluded that heating sufficient to damage spermatogenesis was not associated with dramatic alterations in the integrity of the blood-testis barrier but more with changes in testicular metabolism.


Electrophoretic protein profiles of rat gonads during differentiation.

The protein patterns of fetal rat gonads (14 1/2-21 1/2 days of gestation) were examined by SDS gel electrophoresis. Male gonads contained more protein components at all stages.


A reexamination of endometriosis after pregnancy.

Endometriosis retards the process of conception, but conception does not retard the progression of this disease. When a series of patients with endometriosis after pregnancy were examined, sites of endometriotic involvement and presenting symptoms appeared unchanged. It seems that the effect of pregnancy on this disease is only temporary.


Trisomy-18 and antepartal fetal distress.

Two cases are presented wherein cesarean section was performed because of evidence of intrauterine growth retardation and antepartal fetal distress. Both infants had the trisomy-18 syndrome. Attention is drawn to the fact that the combination of growth retardation and fetal distress sometimes heralds the presence of severe anomalies in the fetus, and it is suggested that cesarean section should not be performed before one attempts to rule out such life-threatening abnormalities.


Synthesis and body distribution of several iodine-131 labeled centrally acting drugs.

1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (3B), 4-iodo-2,5-dimethoxyphenylethylamine (3A), and 1-(4-iodo-2,5, dimethoxyhenyl)-2-aminobutane (3C) have been synthesized with 131I. Labeled iodine monochloride reacts with the appropriately substituted phthalimide at the aromatic 4 position, and the phthalic acid group is removed with hydrazine. Body distribution was measured in rats; the most prominent difference between the three compounds was a much greater concentration in the lung with 3b than with 3a or 3c. gamma-Ray scintigraphs of 3a-c in rats and of 3b in a dog indicate an uptake by the brain similar to that of the bromine analogue of 3b (DOB) in humans. [82Br]-DOB has been suggested as a potential brain scanning agent for nuclear medicine; 3b would have the advantage over DOB of providing the superior gamma-ray imaging properties of 131I or 123I.


Contragestational agents. 1. Steroidal O-aryloximes.

The preparation of a series of O-aryloximes of various steroids by two different routes is described. These compounds were prepared by reacting a keto steroid with a substituted O-arylhydroxylamine in the presence of an acid catalyst or, alternatively, by the reaction of a steroidal oxime with a substituted aryl halide in the presence of a suitable base. These compounds were examined for their ability to interrupt postimplantive gestation in female rats. The most significant contragestational activity was seen with compounds in which the basic steroid structure was a 5alpha-androstane and the 3-oxime was of the p-nitrophenyl series. One of the most active compounds in the series (16) was shown to have the ability to terminate pregnancy, when orally administered to rats at 2.5 mg/kg on days 9-12 of gestation. This compound was found to be devoid of androgenic activity at this dose level.


Prostaglandins and congeners. 15. Synthesis and bronchodilator activity of dl-11-deoxy-15- or 16-alkylprostaglandins.

The synthesis of dl-11-doxy-15- or 16-alkylprostaglandins by the conjugate addition of appropriately substituted lithium alanate or lithium cuprate reagents to several cyclopentenones is described as is the preparation of the requisite intermediate (E)-1-iodo-1-alkenyl compounds 4, 22, 23, and 31. The bronchodilator activity of these prostaglandin congeners is presented.


Dibenztroponeacetic and -propionic acids. Potent new antiinflammatory agents.

The syntheses and antiinflammatory assays of some dibenztroponeacetic and -propionic acids and derivatives are described. The most potent compound, d-2-(5H-dibenzo[a,d]cyclohepten-5-on-2-yl)propionic acid, has a potency of ca, 70 times phenylbutazone in the rat carrageenan paw assay and two to three times indomethacin in long-term animal assays. Some beta-dialkylaminoethyl esters of this compound also show high antiinflammatory activity.


Synthesis and hypoglycemic activity of 4-substituted 3-mercaptopicolinic acids.

3-Mercapto-4-methylpicolinic acid one of very few compounds derived from 3-mercaptopicolinic acid (3-MPA) to have hypoglycemic activity. In an effort to find compounds with greater potency than 3-MPA, several 4-substituted 3-mercaptopicolinic acids (4-OMe, OC6H5, SMe, SH, Cl, NH2, Et; 1-7) were prepared and tested in 48-h fasted rats. None was hypoglycemic in this test system after oral dosing of 150 mg/kg.


Antineoplastic agents. 1. N-Protected vinyl, 1,2-dihaloethyl, and cyanomethyl esters of phenylalanine.

A series of N-protected vinyl, 1,2-dihaloethyl, and cyanomethyl esters of phenylalanine was synthesized and these compounds were evaluated for antitumor activity against the growth of Ehrlich ascites carcinoma in CF1 male mice (33 mg/kg/day), Walker 256 carcinosarcoma in Sprague-Dawley male rats (2.5 mg/kg/day), and P388 lymphocytic leukemia in DBA/2 mice (20 mg/kg/day). Structure-activity relationships were evaluated and acute toxicity studies (LD50 determinations) in male CF1 mice were also carried out on selected compounds. Carbobenzoxy-L0phenylalanine vinyl ester (5), N-carbobenzoxy-L-phenylalanine 1,2-dibromoethyl ester (12), and N-carbobenzoxy-L-phenylalanine cyanomethyl ester (8) were found to be very potent inhibitors of Ehrlich ascites tumor growth at nontoxic doses cited above. Compounds 5 and 12 also tripled survival time in the Walker 256 system. LD50 values for compounds 5, 12, and 8 were greater than 2000 mg/kg (greater than 6.15 mmol/kg), 74 mg/kg (0.15 mmol/kg), and 150 mg/kg (0.44 mmol/kg), respectively.


Antineoplastic agents. 2. Structure-activity studies on N-protected vinyl, 1,2-dibromoethyl, and cyanomethyl esters of several amino acids.

Previously reported work on N-protected activated esters of phenylalanine has been extended to include N-protected vinyl, dibromoethyl, and cyanomethyl esters of several other amino acids. These compounds have been synthesized and evaluated in Ehrlich ascites carcinoma, Walker 256 carcinosarcoma, and and P388 lymphocytic leukemia tests. Among compounds tested were derivatives of tyrosine, tryptophan, glycine, leucine, proline, aspartic acid, glutamic acid, 4-aminobutyric acid, and 6-aminocaproic acid. Compounds of greatest potential interest from this study are N-carbobenzoxyglycine 1,2-dibromoethyl ester and N-carbobenzoxy-L-leucine 1,2-dibromoethyl ester. Both compounds were highly active in Ehrlich ascites test systems (33 mg/kg/day). The glycine derivative was also active in the Walker 256 test (2.5 mg/kg/day. Values for LD50's in mice were 148 mg/kg (0.37 mmol/kg) and 225 mg/kg (0.50 mmol/kg) for glycine and leucine derivatives, respectively; therefore, these compounds do not appear to be toxic at effective dose levels.


Carbon-13 nuclear magnetic resonance investigations into the interactions of bisulfite with pyrimidine nucleosides and nucleotides.

Carbon-13 NMR is utilized to demonstrate the attack of bisulfite anion on uridine, 5-fluorouridine, and uridine 5'-monophosphate. The attack produces a pair of diastereomeric adducts similar in structure to those seen in the uracil series. Intensity data from the equilibrium system give an estimate for the individual equilibrium constants. Thymidine and thymidine 5'-monophosphate show no evidence of nucleophilic attack by bisulfite. This evidence indicates that bisulfite addition to nucleosides and nucleotides models the enzymatic methylation of uridine by the enzyme thymidylate synthetase better than the uracil bisulfite system.


Parasympatholytic (anticholinergic) esters of the isomeric 2-tropanols. 1. Glycolates.

The 38 esters in Table I were prepared from the four isomeric 2-tropanols and a variety of racemic glycolic acids and their optical isomers. Anticholinergic activity in mice was measured in the peripheral nervous system (mydriasis) and in the central nervous system (anti-tremorine) and compared with that of atropine, scopolamine, and racemic 2-quinuclidinyl benzilate. The results (Table III) showed that several esters (such as 8, 12, 14, and 21) had significantly greater activity in both the peripheral and central nervous systems than did the reference compounds. Esters of (+)-2alpha-tropanol were more potent than those of either its epimer (-)-2beta-tropanol or its optical isomer(-)-2alpha-tropanol. Esters derived from (-)-glycolic acids were uniformly more potent than those from the (+)-glycolic acids. Esters of (+)-2alpha-notropanol and five of its N-substituted derivatives had markedly decreased activity. Peripheral/central activity ratios and time-activity profiles for five active compounds are discussed and compared with those of the reference compounds.


Potent reversible anticholinesterase agents. Bis- and mono-N-substituted benzoquinolinium halides.

A number of bis- and mono-N-substituted benzoquinolinium salts and their analogues were prepared and evaluated as inhibitors of acetylcholinesterase (AcChE) and butyrylcholinesterase (BuChE). These compounds were also used to help identify some of the morphologic characteristics of the surface at or near the active sites of the cholinesterases. The shape, size, configuration, and conformation of the onium moieties of the quaternary ammonium compounds were found to be the important factors in their anticholinesterase activity. A high concentration of the positive charge of the quaternary ammonium compound is not a critical factor for the cholinesterase inhibitory activity. The order of decreasing potency of cholinesterase inhibition of the benzoquinolinium compounds was found to be acridinium greater than phenanthridinium greater than 5,6-benzoquinolinium greater than 7,8-benzoquinolinium. The inhibitory activity of the monobenzoquinolinium halides against cholinesterases is influenced by the N-substituent. A bis-quaternary ammonium compound with a flexible bridge that links the two nitrogen atoms was found to be more potent in inhibiting AcChE and less potent in inhibiting BuChE than a bis-quaternary ammonium compound with a rigid bridge. The acridinium and phenanthridinium derivatives of the benzoquinolinium compounds are very potent reversible inhibitors against both AcChE and BuChE.


Molecular structure of thyroxine analogues. Crystal structure of 3,5,3'-triiodothyroacetic and 3,5,3',5'-tetraoiodothyroacetic acid N-diethanolamine (1:1) complexes.

Crystallographic data demonstrated that conformations of thyroid hormones and their derivatives in which the phenyl rings are either skewed (phi,phi'; +/-90,0 degrees) or twist-skewed (phi,phi'; +/-108, +/-28 degrees) are energetically favored. Acetic acid metabolites are consistently observed in the skewed conformation whereas their parent hormones are observed in the twist-skewed conformation. These preferences are manifestations of long-range conformational transmission and together with plasma protein binding data may indicate a site-specific preference for the skewed vs. twist-skewed conformation. These findings result in part from the crystal structure determinations of the N-diethanolamine (1:1) complexes of the active thyroxine metabolites 3,5,3'-triiodothyroacetic acid (T3AA) and 3,5,3'5'-tetraiodothyroacetic acid (T4AA) which are reported here. The conformation of the 3'-iodine in the hypocholestermic agent T3AA is distal, the biologically preferred conformation, and the overall conformation of T3AA is transoid, while that of T4AA is cisoid.


Structure-activity studies on hallucinogenic amphetamines using molecular connectivity.

A series of ring-substituted hallucinogenic amphetamines has been analyzed using molecular connectivity. A correlating equation has been found between potency and connectivity terms. The equation permits an interpretation of SAR. The equation is capable of predicting potency for amphetamines not in the list and mescalines and tryptamines.


Prostaglandins and congeners. 16. Synthesis and bronchodilator activity of dl-11-doexy-3-thiaprostaglandins.

The interesting bronchodilator activity of certain dl-11-deoxy-3-thiaprostaglandins and their preparation by the conjugate addition of appropriately substituted (E)-1-alkenyllithio cuprate reagents to requisite cyclopentenones are described.


3-(3-Substituted prop-1-enyl)cephalosporins.

The synthesis of cephalosporin derivatives possessing a 3-substituted prop-1-enyl group at the 3 position is described. This was achieved using the reaction of vinylmagnesium chloride with the 3-formyl derivatives 1 to give a vinylcarbinol which readily underwent allylic rearrangements to give the desired side chains. The new derivatives exhibited potent in vitro and in vivo antibacterial activity.


Analogues of sparteine. 5. Antiarrhythmic activity of selected N,N'-disubstituted bispidines.

A series of seven N,N'-disubstituted bispidines, structurally analogous to the inner (B and C) rings of sparteine (1) and encompassing a range of lipophilicity in which 1 was centered, has been compared to 1 in regard to antiarrhythmic potency and acute toxicity. Several of the bispidines were of comparable potency, and all but one were somewhat less toxic than 1. The ability of the mononitrate salts of 1 and bispidines 6 and 7 to bind calcium and magnesium cations in Me2SO-d6 solvent has been evaluated by proton magnetic resonance analysis. No binding could be demonstrated under these conditions, which suggested that pharmacologic effects of these compounds may be due to properties other than direct binding of these cations.


Potential histidine decarboxylase inhibitors. 1. alpha- and beta-substituted histidine analogues.

Histidine analogues with alkyl substitution at Calpha and Cbeta were prepared as potential inhibitors of specific histidine decarboxylase. Activity was assessed in vitro using extracts of rat pyloric stomach and a radioisotopic assay of 14CO2 evolved from carboxyl-14C-labeled histidine. alpha-Substituted analogues (C2-C4) including 2-hydroxyethyl were less potent than alpha-methylhistidine; the alpha-n-butyl analogue was completely inactive at 10(-3) M. Similarly, beta,beta-dimethylhistidine and homohistidine failed to exhibit activity at 10(-3) M.


Potential carcinostatics. Synthesis and biological properties of d- and 1-beta,beta-difluoroaspartic acid and beta,beta-difluoroasparagine.

Di-tert-butyl beta,beta-difluorooxaloacetate, prepared by fluorination of di-tert-butyl oxaloacetate with perchloryl fluoride, was converted to di-tert-butyl beta,beta-difluoroaspartate via its O-methyl oxime, followed by reduction. The tert-butyl ester was hydrolyzed to give a mixture of dl-beta,beta-difluoroaspartic acid, which was resolved via its brucine salts. dl-Difluoroaspartic acid was converted into beta,beta-difluoroasparagine by monoesterification and subsequent ammonolysis. Racemic beta,beta-difluoroaspartic acid inhibits aspartate aminotransferase. Cell growth of 3T3-F cells was slightly inhibited by l-beta,beta-difluoraspartic acid while the d enantiomer was without effect in this test system.


Bradykinin potentiating and sensitizing activities of new synthetic analogues of snake venom peptides.

The structural requirements for prolonged residual ("sensitizing") activity in bradykinin-potentiating peptides (BPP's) were investigated through a study of seven synthetic BPP's including three not previously described: [Lys6]-BPP9a, [Gly6]potentiator B, and [Lys6,Gln8]potentiator B. The quantitation of the sensitizing activities in the isolated guinea pig ileum indicated that the structural requirements for bradykinin potentiation and for sensitization were not the same. The most potent sensitizers were potentiator B and [Lys6]-BPP9a.


(+)- and (-)-3-Methoxycyproheptadine. A comparative evaluation of the antiserotonin, antihistaminic, anticholinergic, and orexigenic properties with cyproheptadine.

The synthesis and resolution of (+/-)-3-methoxycyproheptadine [(+/-)-4] are described. As a peripheral serotonin antagonist, (+/-)-4 was found to be one-half as potent as cyproheptadine (1b). The peripheral anticholinergic and antihistaminic activities as well as the orexigenic property of (+/-)-4 are less than those of 1b. A further comparison of the enantiomers (+)-4 and (-)-4 shows that all of the anticholinergic activity of (+/-)-4 resides solely in the dextrorotatory enantiomer, (+)-4, while the antiserotonin activity, which is similar to that of 1b, resides in the levorotatory enantiomer, (-)-4. Antihistaminic and orexigenic activity also resides in (-)-4 but these properties are reduced compared to those of 1b.


Aminobenzoic acid diuretics. 9. 3,4-Disubstituted 5-acylaminobenzoic acids and related compounds.

A number of 3,4-disubstituted 5-acylamino-, 5-alkylamino-, and 5-ureidobenzoic acids corresponding to previously described 3,4-disubstituted 5-sulfamoylbenzoic acid diuretics were prepared and screened for their diuretic properties in dogs. The tabulated results reveal that several 3,4-disubstituted 5-formamido and 5-acetamidobenzoic acids possess considerable diuretic potency demonstrating that a 5-sulfamoyl or 5-methylsulfonyl substituent is not a necessity for potent diuretic activity of 3,4-disubstituted benzoic acids. 4-Benzoyl-3-benzyloxy-5-formamidobenzoic acid, one of the mo-t potent compounds of the present series, is approximately one-tenth as potent as bumetanide. The dose response and diuretic pattern indicate high-ceiling diuretic activity and suggest a mode of action similar to that of bumetanide.


Antileukemic activity of derivatives of 1-phenyl-2,5-dimethyl-3,4-bis(hydroxymethyl)pyrrole bis(N-methylcarbamate).

Treatment of N-aryl-N-acetylalanine derivatives, 3, with acetic anhydride-dimethyl acetylenedicarboxylate gave the dimethyl N-aryl-2,5-dimethylpyrrole-3,4-dicarboxylates, 4. Reduction of 4 and acylation of 5 gave 2a-j and 6. All of the title compounds 2a-j and 6 showed significant reproducible activity in the P388 in vivo antileukemic assay.


Quinazolines and 1,4-benzodiazepines. 81. s-Triazolo[4,3-a][1,4]benzodiazepines by oxidative cyclization of hydrazones.

s-Triazolo[4,3-a][1,4]benzodiazepines bearing various substituents in the 1 position were prepared by oxidative cyclization of the appropriate aldehyde hydrazones of 2-hydrazinobenzodiazepines. Diethyl azodicarboxylate and activated manganese dioxide were used as oxidizing agents. The new triazolo compounds were active in the CNS tests but none of them reached the potency of the known triazolobenzodiazepines.


Chemoimmunotherapy of cancer. 3. Analytical measurement of chemical half-lives of monofunctional alkylators.

The objective of this study is the measurement of the rates of hydrolysis of a series of chloroethyl sulfide derivatives, under stimulated physiological conditions. Interferences encountered with the conventional spectrophotometric method prompted the use of a rapid-response, chloride selective electrode. This probe was readily capable of monitoring the hydrolytic rate, which is identical with the rate of chloride ion formation. Since the desired subsecond half-lives were not achieved by any of the compounds, factors influencing the rates were investigated. The results suggest that the rate-controlling cyclization step may be inhibited, due to coordination of undissociated protonic functional groups on the aromatic portions of the structures with the lone-pair electrons on sulfur.


Synthesis of carboxyarylindoles and benzofurans as nonsteroidal antiinflammatory agents.

2-Carboxyaryl-substituted dihydrobenz[e]indoles, tetrahydroindoles, and tetrahydrobenzofurans have been synthesized as structural analogues of fendosal, a new antiinflammatory agent, and tested in the carrageenan-induced rat paw edema assay. Two of these, 2-(3-carboxy-4-hydroxyphenyl)-3-phenyl-4,5-dihydrobenz[e]indole and 1-(n-butyl)-2-(3-carboxy-4-hydroxyphenyl)-4,5,6,7-tetrahydroindole, were found to have significant activity, albeit of a lower order than fendosal.


Hypolipidemic activity of 5-aryl-3-methylvaleric acid derivatives.

Several 5-aryl-3-methylvaleric acid derivatives have been shown to be more potent hypolipidemic agents than the previously reported 5-(4-biphenylyl)-3-methylvaleric acid (1). The most active compound in this series was 5-(4-phenylsulfonylphenyl)-3-methylvaleric acid (10) which lowered serum cholesterol levels 45% and serum triglyceride levels 60% in normal rats. Significant lowering of the serum triglyceride levels was the predominant effect noted with most of the compounds tested.


H-Y antigen and the growth of the dominant gonad.

The evolutionary conservation of H-Y antigen and its expression in the heterogametic sex regardless of whether this is male or female must mean that the antigen is associated with a common denominator underlying the development of mammalian testes and avian ovaries. It is suggested that one such common denominator is an enhanced growth rate of the dominant heterogametic gonad at a critical stage of its development.


Lead levels in human placentae from normal and malformed births.

Placental lead levels were studied in a series of Birmingham births classified by stillbirth, neonatal death, or survival beyond one week. There was an appreciable range of lead levels even in normal births (0.15-3.56 microgram/g) but nevertheless average results showed a pronounced excess of lead in those who failed to survive both birth and the neonatal period. There was no association of placental lead with impaired birthweight among survivors but, in common with other authors, we noted a seasonal variation. The placentae from Indian women had similar lead levels to those from European women and lower values were found in the normal sibs of stillbirths and neonatal deaths. The possibility is discussed that under conditions of impaired fetal health in late pregnancy the placenta may concentrate lead.


Severe lower limb malformation associated with other deformities and death in infancy in two brothers.

Two brothers with severe and rare lower limb malformations but normal upper limbs are described. Both brothers had glans hypospadias and they died in early infancy. In the first brother the limb malformation was a severe deformity of the right foot which was split and of rockerbottom shape with oligosyndactyly. In the second brother the right limb below the knee was more severely deformed while only the toes were involved in the left limb. Details of the clinical and pathological findings are described. The most likely mode of inheritance of this rare syndrome is autosomal recessive or X-linked recessive with variable expressivity.


Maxillofacial dysostosis.

Four individuals in a single family affected with maxillofacial dysostosis are reported. Maxillary hypoplasia, delayed onset of speech, and poor development of language skills without associated hearing loss are the main characteristics of the syndrome which is transmitted as an autosomal dominant. Cephalometric analysis and speech and hearing evaluation of our patients confirmed the above findings.


Probable autosomal recessive Marfan syndrome.

A probable autosomal recessive mode of inheritance is described in a family with two affected sisters. The sisters showed the typical picture of Marfan syndrome and were of normal intelligence. Both parents and all four grandparents were personally examined and found to be normal. Homocystinuria was ruled out on repeated examinations. This family suggests genetic heterogeneity in Marfan syndrome and that in some rare families the mode of inheritance may be autosomal recessive.


Two pericentric inversions of human chromosome 11.

A pericentric inv(11) (pl5q23) detectable by G-, Q-, and R-banding and occuring in 1 member of each of 3 generations of a family is described. In another family studied by several banding methods in search of chromosomal markers, a pericentric inv(11) (p11q11) was found. It was detectable only by C-banding, the darkly staining band being located on the short-arm side of the centromere. The reasons for defining this aberration as an inversion rather than a location variant are outlined. This inversion occurred in 9 members of 3 generations of a large family. There was no clear-cut evidence of any clinical consequences of these inversions either in heterozygotes or their offspring.


Mosaicism presumably related to a Y/6 translocation in a boy with multiple congenital abnormalities.

A 3 1/2-year-old boy was referred for chromosomal evaluation because of mental and developmental retardation, peculiar facies, and abnormalities of the extremities. Karyotype analysis disclosed the presence of 46 and 47 chromosome cell lines. The 46 chromosome line contained 4 normal G group chromosomes and an abnormally small Y identified by G banding. Further investigation with Q and C band techniques revealed that the missing segment of the Y, the distal long arm, had been translocated to the end of the long arm of a number 6 chromosome. This de novo rearrangement appeared to be balanced and was found in all cells examined. The 47 chromosome line, which had a frequency of 10% in the patient's leucocytes, was identical to the 46 line except for the presence of an additional copy of the small chromosome. The morphology and banding patterns of the two small acrocentrics in the aneuploid line were found to correspond to those of the der (derivative) Y in the euploid line. The cytogenetic findings suggest that the translocation was followed by non-disjunction of one of its products resulting in mosaicism. Possible causes for the clinical and karyotypic abnormalities are discussed.


A dicentric no. 15 chromosome with two satellite regions.

A case of an inherited chromosome no. 15 with two centromeres and two satellite regions is described and its origin postulated. The chromosome appears to have no clinical significance.


Leprechaunism with mosaicism 46, XX/47, XX extra ring chromosome.

A case of leprechaunism with a chromosomal abnormality is reported. The patient was a female infant, born to healthy, consanguineous young parents. Her course was one of extreme marasmus, with death at 3 months of age. She presented the classical features of the syndrome and chromosome mosaicism 46, XX/47, XX, +r(?). It was not possible to identify the origin of the extra ring chromosome. It is difficult to establish the role of such a cytogenetic finding in the aetiology of the syndrome.


Scanning electron microscopy of freeze-dried aortic elastin.

As part of a larger project aimed at claryfying some of the uncertainties that exist concerning the structural basis for an explanation of the mechanical behaviour of elastin, an examination was made of purified porcine aortic elastin under the scanning electron microscopy. In order to avoid structural changes caused by impregnation with organic solvents, specimens were prepared directly from their water-saturated state by either air-drying of freeze-drying processes. Comparison of the results obtained by these techniques demonstrates that freeze-drying of elastin has the advantage of enhancing fine detail, minimizing distortion and reducing specimen shrinkage.


Ultrastructure of unfixed plasma membranes in ultrathin frozen sections.

Ultrathin sections of unfixed kidney tubular cells were obtained by cryo-ultramicrotomy using the 'wet' method. The results showed that extremely thin sections permit high resolution studies on unfixed plasma membranes. Structural units on the inner surface of the plasma membrane could be detected.


The free swimming Pipa larvae, with a review of pipid larvae and pipid phylogeny (Anura: Pipidae).

This paper describes the morphology of the free swimming Pipa larvae, compares them with Xenopus, Hymenochirus, and to some extent, Rhinophrynus larvae, and presents a morphological diagnosis of pipid larvae. Pipa and Xenopus have very similar chondrocrania. Hymenochirus is superficially different but has the same diagnostic features. The differences appear related to its small size and predatory habitus. Other aspects of anatomy, especially the filter apparatus are very different in each genus. The filter apparatus of Pipa is somewhat reduced and seems modified for the retention of relatively large (20+ microns) particles. Similar adaptations may have been annectant to predations in Hymenochirus, which lacks a filter apparatus. However, varying states of seven character complexes, which cut across the varying ecology, show that there are two basic pipid lineages, each currently confined to Africa or South America, respectively. Recent finds of fossil South American Xenopus indicate that these two lineages separated before the continents did. This does not warrant the recognition of two subfamilies because Xenopus and Hymenochirus are too different. Pseudhymenochirus is not an intermediate between them; it is primitive Hymenochirus. Eight character states separate pipid and rhynophrynid larvae.


Nucleolar reorganization in cells of the kidney of the rat and its relation to aging.

A process of nucleolar reorganization apparently identical to that encountered in intestinal epithelial cells (Adamstone and Taylor, '72) develops in kidney cells of aging rats. The polymorphic nucleoli of young tubule cells soon change to amphinucloeli and, while terminal nucleolar reorganization is delayed in cells of collecting tubules, in the nephrons nucleoli soon begin to undergo terminal reorganization becoming bipartite structures with separate plasmosomes and karyosomes. This suggests disruption of the DNA-dependent RNA protein transcription system and failure to maintain the flow of messenger RNA into the cytoplasm. Old cells are not discarded immediately from the kidney tubules and they retain much rough endoplasmic reticulum, numerous ribosomes and polysomes and large plasmosomes. Thus a high RNA concentration is known to develop in old kidney tissue while protein synthesis is also known to be low (Kanungo et al., '70; Buetow and Ghandi, '73). Nucleolar counts show gradual increase in bipartite nucleoli at the expense of amphinucleoli and in the senescent kidney bipartite nucleoli predominate. It is suggested that nucleolar reorganization, with final separation of plasmosomes and karyosomes, includes the process of nucleolar segregation and is triggered by some innate nucleolar mechanism in response to encoded genetic information stored in the nucleolus during nucleogenesis. At this time both DNA and RNA are incorporated into the developing nucleolus. It is also to be noted that two shifts in nucleolar dominance occur with advancing age. These may be fundamental to the process of aging and to the onset of senescence. Furthermore, the changes in dominant nucleolar types are the direct result of the process of nucleolar reorganization.


Infrared spectral characterization of peptidic material produced by ionizing radiation in aqueous cyanides.

Oligomers formed by ionizing radiation in aqueous cyanide solutions, under various experimental conditions, have been characterized by infrared spectroscopy. IR bands appear in the region known to be characteristic for amides and peptides. The results are discussed in relation to radiation-induced formation of peptidic material and the potential role of ionizing radiation as an energy source for some processes in prebiotic molecular evolution.


Evolutionary changes of alpha-crystallin and the phylogeny of mammalian orders.

The sequences of the A chains of the eye lens protein alpha-crystallin from seventeen mammalian species were compared. They showed a generally slow rate of evolution, but with marked variations in different lineages. Most substitutions have occurred in the C-terminal part of the chain, which probably forms part of the surface of the alpha-crystallin aggregate. The ancestral sequence method of Dayhoff revealed interesting indications about the phylogenetic relationships between the eleven mammalian orders that were represented by the investigated species. Most evident was the divergence of marsupial and placental orders. A notable resemblance between the hyrax and elephant sequences was observed, setting them apart from the ungulates, including whale. Primates, rodents, lagomorphs, insectivores and tupaiids seem to derive from a common stem group. These phylogenetic inferences are discussed in relation to current palaeontological and taxonomical opinions, and compared to evidence from other protein sequence data.


Formation of nucleoside 5'-phosphoramidates under potentially prebiological conditions.

Adenosine 5'-phosphoramidates form when solutions containing adenosine 5'-polyphosphates pnA (n greater than or equal to 3) or P1, P2-diadenosine 5'-diphosphate and amines are allowed to dry out. Mg ions catalyze these reactions. We have studied systems containing ammonia, imidazole, glycine, ethylenediamine and histamine. The yields of adenosine 5'-phosphoramidates range from 10-50% based on the nucleotide. The prebiotic significance of the reactions is discussed.


On the cysteine and cystine content of proteins. Differences between intracellular and extracellular proteins.

Analysis of published data on the cysteine and half-cystine content of proteins indicates that most intracellular proteins may be classified as sulfhydryl proteins (those containing cysteine but little or no half-cystine) and that such sulfhydryl proteins have a low cysteine content. The mean systeine content found for 32 intracellular mammalian proteins was 1.6% and intracellular proteins of many bacteria have similar or lower values. Extracellular mammalian proteins are primarily disulfide proteins (those containing half-cystine but little or no cysteine) have a high half-cystine content, the mean value found for some 34 extracellular mammalian proteins being 4.1%. This is contrasted with many of the extracellular proteins from facultative bacteria which are cyst(e)ine-free proteins, being lacking in both cysteine and half-cystine. These and related observations are interpreted in terms of the evolution of life in a reducing atmosphere and the subsequent transition to an oxidizing environment. It is suggested that disulfide proteins evolved primarily after the accumulation of oxygen in the atmosphere.


Stereoselective crystallization induced by traces of dissolved optically active impurities.

Isothermal crystallization of D,L-sodium-ammonium tartrate with traces of different impurities admixed shows that the added chiral contaminations produce a preferential crystallization of the tartrate isomer of same handedness. The critical lowest concentration of effective seeding agents is 0.1-0.5%. 1% optically active excess material induces 1.0-3.6% optical purity in the deposited crystals. An analysis of the relevant data reported so far gives similar figures in different crystallization systems. The relation of the results to the suggested lattice energy difference between enantiomers is discussed.


Molecular evolution of snake venom toxins.

Phylogenetic trees were constructed for 62 venom toxins of snakes of Proteroglyphae suborder using matrix method. The resulting tree from Minimum Spanning Tree-Cluster Analysis technique had the lowest "percent deviation" (8.55). The taxonomic relationship of these toxins agrees very well with zoological opinions. However, the appearance of the tree did not directly provide a plausible evolutionary model for the toxins. A model was derived from nodal ancestral sequence calculations, comparisons between intra- and intergenerical rates of amino acid change, and generally held ideas about protein evolution. According to the model, short neurotoxin is the ancient form of snake venom toxins. The courses of evolution leading to the present intraspecific homologous toxins are explained by gene duplication and allelomorphism.


Endosymbionts and mitochondrial origins.

The possibility is put forth that the mitochondrion did not originate from an endosymbiosis, 1-2 billion years ago, involving an aerobic bacterium. Rather, it arose by endosymbiosis in a much early, anaerobic period, and was initially a photosynthetic organelle, analogous to the modern chloroplast. This suggestion arises from a reconsideration of the nature of endosymbiosis. It explains the remarkable diversity in mitochondrial information storage and processing systems.


The restriction of codon ambiguity on the basis of known variants.

The genetic code may be used to formulate the nucleotide sequence of a messenger RNA from the known amino acid sequence of a protein. Unfortunately, the degeneracy of the code means that there will be ambiguity in the nucleotide assignments in a third or more of the positions. A simple procedure is given that utilizes the information of known genetic variants to reduce that ambiguity. Problems associated with silent polymorphism are treated. The human alpha and beta hemoglobins are used to exemplify the technique. A total of 68 nucleotides in the two sequences are thereby made less ambiguous. One reduction leads to a nucleotide inconsistent with the result of the recently published beta hemoglobin sequence.


The Gestalt awareness-expression cycle as a model for sex therapy.

Conceptual models and treatment modalities generally used in Gestalt therapy are specifically applicable to sex therapy. Healthy sexual functioning requires self-regulation in which the person becomes aware of the dominant need in the situation and expresses himself to satisfy that need and to complete the Gestalt. The Gestalt awareness-expression cycle is a model for understanding both the processes of sexual functioning and dysfunction and of the therapeutic encounter. The concepts of awareness, excitement, action, and contact as components of the cycle are related conceptually both to modes and points of interruption of self-regulation and to specific treatment modalities and methods. Three major modalities of Gestalt therapy, awareness, experiment, and contactful encounter, and illustrative Gestalt methods are introduced in the context of sex therapy.


The evaluation of sexual health services in a medical setting.

An interdisciplinary Sexual Health Services unit has been established at the University of Minnesota Medical School that offers counseling and treatment programs for a wide variety of sex-related concerns and problems. The programs are based on the principles of responsibility for self, permission to be sexual, the use of reeducation, the facilitation of increased awareness in clients, and structured behavior change. The programs have been evaluated according to client satisfaction with the extent to which they have met pretreatment goals and according to results of pre/posttesting with objective instruments. One year follow-up results from 131 clients and immediate posttreatment results from 411 clients show positive change in a large majority of cases.


Factors influencing contraceptive behavior of single college students.

This study investigated the premarital contraceptive behavior of 222 male and female college students. Contraceptive practice was examined in relation to dating patterns, level of emotional involvement with the sex partner was heightened, the intercourse was planned, and the individual and prior sexual experience.


Use of statistics when examining lifetime studies in rodents to detect carcinogenicity.

The lifetime assay for carcinogenicity that subjects groups of 50 animals per sex per dose to three doses and a control is examined for its statistical properties. Using the standard formulation of tests of hypothesis, it is shown that there is a 20-50% chance of having a false positive and that it is possible to define a "weak carcinogen" in terms of the degree of effect that would produce a false negative less than 5% of the time. Whether hypothesis testing is a proper use of statistics in this context is questioned, and alternatives are proposed.


A fast-screening procedure for testing the effects of pollutants in mammals.

A compartmental analysis of r the radiorespirometric study of the metabolism of [14C]glucose is described. The model is applied to the study of the effects of CH3HgCl on this metabolism. Implications of the agreement between experiment and the mathematical model for the development of fast-screening experiments for detecting in vivo effects of pollutants and toxins are discussed.


Effects of chlordane isomers administered to female mice during the neonatal period.

In consideration of the influence that chlorinated hydrocarbon insecticides may exert on mammalian physiology, the present study was performed to investigate the effects of neonatal chlordane administration on body growth and endocrine development in female mice. Mice receiving 0.075 or 0.15 mg of alpha or gamma chlordane on day 2, 3, and 4 of life were observed to have growth rates depressed to varying extents depending on the concentration or the type of isomer that was utilized. Eye and vaginal opening in the neonatally treated mice were observed to be delayed to varying degrees, which were dependent on which isomer was used. The total effects observed in the neonatally treated mice were not found to reflect a dose-related response.


Endrin: effects on the entire life cycle of a saltwater fish, Cyprinodon variegatus.

The sheepshead minnow (Cyprinodon variegatus) was continuously exposed for 23 wk to the organochlorine insecticide endrin, from the embryonic state through hatching until adulthood and spawing. The resultant progeny were monitored to determine the effects of the toxicant on their survival, growth, and reproduction. Average measured exposure concentrations were O (control), 0.027, 0.077, 0.12, 0.31, and 0.72 microgram/liter. Embryos exposed to 0.31 and 0.72 microgram/liter hatched early; all fry exposed to 0.72 microgram/liter died by day 9 of exposure. At 0.31 microgram/liter, fry were initially stunted and some died. Survivors seemed unaffected until maturity, when some females died during spawning; fewer eggs were fertile and survival of exposed progeny decreased. No significant effects were observed th roughout this fish's life cycle at an exposure concentration of 0.12 microgram/liter. Four-week-old juvenile fish accumulated 2,500 times the concentration of endrin in the exposure water; adults, 6,400 times; and their eggs, 5,700 times. The specific application factor (calculated by dividing the limits on the maximum acceptable toxicant concentration, greater than 0.12 and less than 0.31 microgram/liter, by the concentration lethal to 50% of the juvenile fish in 96 hr, 0.34 microgram/liter) ranged from 0.35 to 0.91. To our knowledge this is the first toxicity test carried out through the entire life cycle of an oviporous esturarine fish. Data from this experiment and from experiments with another estuarine fish and four freshwater fish all demonstrate that there is little difference between endrin concentrations that produce acute effects and concentrations that do not affect the fish in chronic exposures lasting four or more weeks.


High levels of endogenous 1,3-butanediol in the blood of a man after ethanol ingestion.

A young man was found to have 1,3-butanediol in his blood, much more after ethanol ingestion. This substance reacted in the enzyme procedure for measuring blood alcohol, giving falsely high values. The 1,3-butanediol was detected by gas chromatography.


Tissue toxicity of antiseptic solutions. A study of rabbit articular and periarticular tissues.

The gross, histologic, and biochemical effects of four commercially available antiseptic solutions on rabbit knee articular and periarticular connective tissues were investigated. Rabbit knee joints were injected with 2.0 cc of either Betadine prep solution, Betadine scrub solution, pHisohex or 3% hexachlorophene. The opposite knees were injected with sterile saline. All animals were injected three times at 48-hour intervals and sacrificed 10 days after the last injection. The solutions containing detergents, Betadine scrub, and pHisohex caused severe gross and histologic damage to articular cartilage, synovia, and muscle. The hexachlorophene loss solution caused moderate histologic damage, but caused articular cartilage ground substance. Betadine prep solution caused only minimal gross and histologic damage, without any biochemical evidence of articular cartilage damage. If antiseptic solutions are to be used in irrigating or packing joint injuries, the use of Betadine prep is recommended.


Hang gliding injuries in California.

Hang gliding continues to grow rapidly despite an increasing awareness of inherent risks. This report describes 144 injuries and 37 deaths in California during the period 1973 through 1975. More accidents were caused by inflight errors of judgment than by equipment failure. Nonfatal injuries showed a surprising number of severe upper extremity and spine injuries, while fatally injured pilots had combined head, neck, and chest trauma. A distinction between pilot education and experience is important. Improved safety equipment and education are recommended.


An immunosuppressive factor from serum of thermally traumatized patients.

An immunosuppressive factor was isolated and partially purified from a fraction of the serum of acute thermally traumatized patients which contained primarily albumins. The factor proved to be either a small protein or a peptide of molecular weight less than 10,000. It inhibited migration of peripheral blood leukocytes of thermally traumatized patients, and of guinea pig peritoneal macrophages. In the presence of the serum, it caused the lysis of peripheral lymphocytes from thermally traumatized patients, and depressed mitogenic stimulation of normal human peripheral lymphocytes. It had no effect on migration, and did not lyse peripheral blood lymphocytes of healthy subjects.


Relationship between trauma to the extremities and stomach motility.

Rate of emptying of the stomach before and after injury was studied by feeding dogs with barium and taking X-rays at regular intervals before and following injury. The injured extremity was not protected in the first group of dogs, and was protected by a cast or splint in the second group. The dogs in a third group were sedated with Nembutal. As compared to control the emptying of the stomach after trauma was markedly delayed or even stopped in the first group and was accelerated in the second group. It was very slow before and after trauma in the Nembutal group. The delay noted in the first group was not related to the time of trauma, but to the time of developing severe pain, swelling, and shock. Mechanical immobilization appeared to be the most important method of preventing the delay of emptying of the stomach after injury; sedation slowed down normal function of the stomach.


Fractures of the femoral neck in childhood. Results of conservative treatment.

Experience with nine patients with fracture of the femoral neck in childhood, eight of whom were treated conservatively by closed reduction and fixation with a plaster cast, and one in whom Steinmann pins and open reposition had to be employed to accomplish fixation, is presented in brief. In six children the results were evaluated as good and in three (including the one case of open reduction) as fair. No serious complications were observed. The problem of nonsurgical versus surgical approach is discussed in the light of the relevant literature. It is suggested that while there can be no set rule as to which treatment should be used, conservative management yields results which are comparable with those attained with a more aggressive approach.


Burn epidemiology: a basis for burn prevention.

An appreciation of the causes of burn injury is essential in order to direct burn prevention programs. Toward this goal, 1,564 patients treated at the UCI Burn Center were studied. There were 699 patients admitted acutely and 865 outpatients. The most common cause of thermal injury in both adults and children was scalding. In children scald burns accounted for 42% of the total number of children treated. In children under 4 years old scalds caused 75% of all burn injuries, most in the kitchen. Flammable liquids were responsible for the majority of the severe burns in the adult group (19% of acute admissions). Housefires, while accounting for only 5% of the adults treated, were responsible for 44% of the adult deaths. Continued public education in safety practices at home especially in the kitchen and bath, and with automobiles and outdoor stoves and fires is recommended, as well as planned escapes from homes and use of smoke detectors.


Multiple cardiac injuries secondary to a single stab wound.

A case of multiple cardiac injuries secondary to a single stab wound is described. The extent of the injury was not fully appreciated at the initial surgical intervention and typical clinical manifestations were delayed in appearance. Cardiac catheterization was necessary to confirm the correct diagnosis. After the correct diagnosis was made, surgical repair was successfully performed.


Rupture of the thoracic esophagus from blunt trauma.

A young man with severe multiple injuries following a motorcycle accident was admitted with head and mandible fractures, coma, fracture dislocation at C5-C6 resulting in total leg paralysis, partial paralysis of the right arm and intercostal muscles, and closed chest injury with possible pulmonary contusion. On the fourth day he developed fulminating mediastinitis and massive empyema, and was found to have a ruptured esophagus. Recovery became possible with surgical drainage of the pleural cavity and mediastinum, proximal and distal decompression of the esophagus, antimicrobial therapy, irrigation of the pleural cavity, complete intravenous hyperalimentation, and infusions of salt-poor albumin. The patient was discharged after 95 days, and 7 months after injury is neurologically intact except for a partial right wrist drop. This rare esophageal rupture should be suspected in any chest injury patients, especially those characterized by extreme cyanosis, dyspnea, shock, and prostration incompatible with thoracic cage injury.


Traumatic rupture of a renal cell carcinoma.

After sustaining very minor trauma, a man presented with flank pain and fever. A complete clinical and radiological evaluation led to exploration for suspected ruptured renal carbuncle with perinephric abscess. A ruptured renal cell carcinoma was found. Differential diagnostic considerations include renal tumor, abscess, cyst, and hydronephrotic kidney. Radical nephrectomy is indicated if the contralateral kidney can sustain life. The patient shows no sign of recurrence or metastases 4 months following antibiotic treatment and nephrectomy followed by chemotherapy and radiation of the renal bed.


Traumatic aneurysm of the intrathoracic left carotid artery with cerebral embolization.

The presentation and management of a young male patient with a traumatic aneurysm of the intrathoracic portion of the left common carotid artery from a football injury, complicated by cerebral embolization, is detailed. At operation 6 weeks afterward the aneurysm was isolated and ligated and the patient was discharged 19 days postoperation with plans for physical and speech rehabilitation. At 14 months a chronic subdural hematoma which caused some seizures was removed, and the patient's neurologic status is continuing to improve. This appears to be the first report of an isolated blunt injury to this branch of the aortic arch.


Traumatic arteriovenous fistula of the internal mammary artery.

A rare case of arteriovenous fistula of the left internal mammary artery after blunt chest trauma is described. The patient was seen 3 weeks later because of a pulsating mass which varied in size, over the left midsternal area. Aortography and arteriography showed an aneurysmal sac draining into a vein in the left chest wall and then into the left axillary and neck veins. The fistula was ligated and excised followed by complete recovery. The literature is reviewed and differential diagnosis from congenital heart conditions, A-V shunts of other thoracic wall vessels, and vascular tumors is discussed.


Cervical cytology screening of high-risk patients in Ondo General Hospital, Nigeria.

A prospective study of the cervical smears of 215 women in the high risk group of patients in Ondo General Hospital is analysed, of which 25 (12.0%) had trichomonal vaginitis, 35 (16.2%) had chronic cervicitis, and 25 (12.0%) had atypical smears. This was the first time cervical cancer screening had been performed in this hospital.


Comparative single/dose treatment of hookworm and roundworm infections with levamisole, pyrantel and bephenium*.

One-hundred and forty-five farmers aged 7-45 years who were infected with Ancylostoma duodenale and/or ascaris were treated with a single dose of levamisole, pyrantel, or bephenium. The percentage cure rates were ascaris 100 per cent ahd hookworm 93 per cent for levamisole; ascaris 90 per cent and hookworm 78 per cent for pyrantel; and ascaris 73 per cent and hookworm 81 per cent for bephenium. The 3 drugs were well tolerated. The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy or The Egyptian Ministry of Healty.


Incidence of hypertension in Ahmadu Bello University Hospital Kaduna--Nigeria.

The incidence and pattern of hypertension in General Out Patient Department of Ahmadu Nello University Teaching Hospital, Kaduna have been described. Two thousand nine hundred and fifty adult patients with 1,636 males and 1,314 females, aged 20 to 70 years were examined in this study. One hundred and twelve patients (3.79%) with 47 males (2.87%) and 65 females (4.94%) were found to be suffering from hypertension. The incidence in females was significantly more than in males. The mode of presentation of 112 cases with hypertension has been discussed. Thirty four (30.35%) with 14 males and 20 females were asymptomatic. Sixteen (14.28%) with 7 males and 9 females presented with cardiac failure. Contrary to previous opinion this study has shown that hypertension is probably more common in Northern Nigeria than was previously realized. There appears to be ample justification for further and more detailed study of hypertension in the rural and urban communities in this area.


Neuro-psychiatric manifestations of typhoid.

The clinical pattern of typhoid fever is changing, and in particular the incidence of neuro-psychiartic manifestations is on the increase. In 246 cases of enteric fever we found 124 with confusional states, delirium, coma, generalized myoclonus, Parkinsonian rigidity or psychoses. We further distinguished two major sub-groups with an acute and an insidious onset. The apparent increase in the frequency of neuro-psychiatric complications of typhoid could represent a change in the pathogenicity of S. typhi or the increasing recognition of a biochemical defect caused by a bacterial endotoxins and provoked by poor nutrition.


The rapid diagnosis of cholera.

A simple method is described for the diagnosis of cholera, literally within seconds, and for the typing of the organism within minutes. Diagnosis is made directly by the microscopical examination of a drop of rice-water stool, using immersion dark-ground illumination, with no adjustment whatever of the lighting, condenser, or objective. It uses the miniature microscope, either in the laboratory, or held in the hand in the absence of a bench, for example at the bedside or in the field. The method depends on the characteristic movement of Vibrio cholerae, on this being instantly visible, under the most difficult conditions if necessary, by the automatic adjustment of the immersion dark ground condenser of the miniature microscope, and on the cessation of the movement of the organism within five minutes of adding a drop of the appropriate antiserum. The method is proving of value in remote areas where cholera is unexpected, where time would be lost in sending a specimen to a properly equipped laboratory, and where isolation of a case may be vital; but it is also claimed to be of value even where cholera is expected and where proper laboratory facilities already exist.


Incidence of renal amyloidosis in pulmonary tuberculosis.

Incidences of renal amyloidosis were studied in patients who were in various stages of pulmonary tuberculosis and a three year follow-up gave some opportunity to study the effectiveness of anti-tuberculosis treatment on the course of renal amyloidosis. It was concluded that 9 to 11 per cent of all patients with pulmonary tuberculosis will eventually develop proteinuria due to renal amyloidosis after a certain period of time. It has been postulated that once amyloidosis has extensively involved the kidneys, anti-tuberculous treatment will not cause any regression in the course of renal amyloidosis.


Argemone oil poisoning.

A family of three suffering from Argemone oil poisoning was investigated. The effects of the oil and its toxic alkaloid sanguinarine have been discussed. A test for detecting sanguinarine has been described.


Haemoglobin genotype, ABO blood groups and carcinoma of the cervix.

Genetic factors have been suggested as having a possible aetiological role in the incidence of carcinoma of the cervix. With the high frequency of carcinoma of the cervix in Ibadan as well as the high incidence of sickle-cell trait, the haemoglobin genotypes and ABO blood groups were analysed in patients managed for carcinoma of the cervix uteri in the University College Hospital, Ibadan. No significant association was found between any haemoglobin genotype or blood group and carcinoma of the cervix. The protection afforded against malaria by the haemoglobin S trait does not seem to protect against the development of invasive carcinoma of the cervix.


Osteomyelitis in Nigerian children (a review of 40 cases).

A retrospective study of 40 children with osteomyelitis revealed that the patients presented in hospital late. Therefore chronic osteomyelitis is prevalent in Nigerian children. Sickle cell anaemia is commonly associated with osteomyelitis. Staphylococcus aureus is the comonest organism but salmonella is associated with sicklers.


Surgical wound infection: a comparison between dressed and undressed wounds.

At the University College Hospital, Ibadan, the conventional method of surgical wound dressing is the use of air-tight and relatively water-tight cotton-gauze-elastoplast dressing. This is usually left in place for seven to ten days unless there is evidence of wound infection, in which case the wound is inspected and redressed using the time-consuming sterile technique, in which a box of sterile instruments may have to be shared amongst about 25 surgical patients. A group of 100 patients was randomly selected and this group divided into two. In the first group, A, the surgical wounds were dressed in the usual manner and dressings left for seven to ten days unless there was any evidence of infection. In the second group, B, the wound was left undressed and "uncared" for 24 to 36 hours after surgery. The comparison of the two groups shows that the time-consuming aseptic method of changing and dressing surgically incised wounds 24 to 36 hours after surgery, does not cut down on the rate of wound infection and is probably unnecessary. This may be due to early formation of fibrin at the wound site which offers a protection against invasion of the wound by bacteria. Typhoid perforation of the terminal ileum gave rise to wound infection in all the cases (100%) in the two groups.


A seriological investigation of Q fever in clinical patients.

Results of a serological survey of 507 patients, 301 males and 206 females at the Ahmadu Bello University Teaching Hospital indicated a total 20.5 per cent, or 21.3 per cent in males and 19.4 per cent females, had been exposed to Q fever agent and had circulating antibody against Coxiella burnetii. Most of the positive sera were from patients whose clinical diagnoses were typhoid and pyrexia of unknown origin though these generally are the commonest clinical diagnoses in the hospital. Titres varied from 1:4 to 1:1028 indicating old infections in some patients and acute in others. The results of normal blood donors also showed a 22 per cent positive. It is suggested that the presumptive evidence of the serological tests results be substantiated by isolation of the agent so that a correlation between clinical signs and evidence of Q fever infection be established.


Fatal herpes zoster in Burkitt's lymphoma following contact with chicken pox.

Burkitt's lymphoma presented atypically in a six-year-old Nigerian girl with back pain, oliguria and facial oedema following a fall at school. Two weeks later, she developed bilateral ptosis, hepatomegaly and ascites. Burkitt's lymphoma cells were found in both ascitic and cerebrospinal fluids. She was successfully treated with intravenous cyclophosphamide and intrathecal methotrexate but later developed fatal herpes zoster at the same time as the resident doctor developed chicken pox. Chart's review showed that she had been in brief contact with chicken pox during a short stay in a transit ward prior to full admission.