Discharges of relay cells in lateral geniculate nucleus of the cat during spontaneous eye movements in light and darkness.

1. Discharges of 315 relay cells of the lateral geniculate nucleus (LGN) during spontaneous eye movements were studied in alert cats. 2. When tested in a stationary patterned field, 114 cells showed sustained discharges related to the direction of gaze (S cells) and to local differences in luminance; 109 cells showed transient response to quick shifts of retinal image during saccades (T cells); ninety-two cells showed mixed responses (M cells), i.e. transient responses to rapid shifts of retinal image and sustained firing related to local differences in luminance. 3. Following saccades occurring in the light, T and M cells showed a burst discharge, while spontaneous discharges of S cells were completely suppressed for 150-200 msec. 4. When tested in total darkness, modifications in activity which were apparent in light disappeared completely. This was true for all 315 relay cells. 5. T cells responded to optic chiasm stimulation at shorter latencies (X = 1.15 msec) than S cells (X = 1.77 msec). M cells showed a latency distribution in between those for S and T cells with a mean latency 1.40 msec. 6. When tested with moving grating stimulation, S cells responded in only one manner; with discharges to each stripe of the grating (primary response), while T and M cells showed two different responses: a primary response to a slower motion and a non-specific burst in response to a faster motion. The burst did not reflect the stimulus pattern (secondary response). 7. When tested with diffuse light switched on and off over the tangent screen, S cells showed a sustained response either to light or darkness, whereas T and M cells responded transiently either to the onset or offset of the light, or to both. M cells occasionally showed a mixture of transient and sustained responses either to light or darkness. 8. In over-all response properties, most S cells correspond to X (sustained) cells and most T cells to Y (transient) cells previously known from acute experiments. M cells had intermediate response properties between X and Y cells. 9. Functional roles of these classes of cells in relation to previously proposed functions are discussed.


The effect of aldosterone and the renin-angiotensin system on sodium, potassium and chloride transport by proximal and distal rat colon in vivo.

1. The roles of aldosterone and angiotensin in the direct control of epithelial sodium transport in vivo have been investigated by measurement of electrical p.d. changes and of the fluxes of sodium, potassium and chloride in rat colon, an organ actively involved in electrolyte homoeostasis. Exogenous angiotensin and aldosterone were given by both short- and long-term infusions and endogenous secretion of the hormones was varied by dietary sodium variation and by nephrectomy and/or adrenalectomy. 2. In vitro angiotensin has been shown to influence colonic salt and water absorption but in the present in vivo experiments administered angiotensin had no significant action on p.d. or on the ionic fluxes of the proximal or distal colon. The increase in p.d. produced by infusing aldosterone was unaffected by giving angiotensin concurrently. The effect of sodium depletion in stimulating sodium absorption and potassium secretion was completely abolished by adrenalectomy but was unaffected by nephrectomy. 3. During prolonged infusion of angiotensin into adrenalectomized rats, a small fall in faecal fluid and sodium content was observed, but this change would have little significance in sodium homoeostasis. 4. Aldosterone and sodium depletion stimulated sodium absorption in both proximal and distal colon but significant increase in potassium secretion was demonstrable only in the distal colon. Bicarbonate secretion (by calculation) was unaffected. In the proximal colon, the increased sodium absorption appeared to be accompanied by increased chloride absorption while in the distal colon it was principally the sodium-potassium exchange that was increased. 5. Adrenalectomy reduced potassium secretion in both proximal and distal colon but sodium absorption was only significantly reduced in the proximal colon. 6. It was concluded that there is no evidence that angiotensin in the living animal has a role as an important salt retaining hormone by direct epithelial action. Aldosterone has a considerable effect which is independent of the presence of angiotensin, and which differs in proximal and distal colon in regard to the relative effects on chloride absorption and potassium secretion.


Sweat gland function in isolated perfused skin.

1. A technique for perfusion of skin has been used to investigate a possible neurochemical basis for the different patterns of sweating in domestic animals. Evaporative water loss was measured from excised trunk skin, ears or tails perfused with a nutrient Krebs solution, to which drugs were added as required. Perfused skin was observed to sweat in response to administration of sudorific drugs, and some features of the patterns of sweating were similar to those which could be induced by heating or by drugs in conscious animals. 2. In sheep and goat skin, injections of adrenaline, and to a lesser extent of noradrenaline, elicited brief sweat discharges but these were not sustained when the drugs were infused during 10-20 min. Injections of isoprenaline, carbachol, 5-HT, bradykinin, oxytocin and histamine were all ineffective. 3. Injections of adrenaline into cattle skin evoked longer-lasting sweat discharges, and infusions of adrenaline elicited continuous discharges. Injections of noradrenaline and sometimes of bradykinin caused only brief sweat discharges; other drugs were ineffective. 4. In horse and donkey skin, injections or infusions of noradrenaline, oxytocin and bradykinin elicited brief discharges of sweat. Infusions of isoprenaline caused a continuous and profuse outflow of sweat. Infusions of adrenaline also caused a continuous discharge which was usually biphasic in its onset. Other drugs were ineffective. 5. Assuming that the brief sweat discharges are due to myoepithelial contractions and the continuous discharges to sustained increases in secretion, equine sweat glands seem to have a alpha-adrenergically controlled myoepithelium and a beta-adrenergically controlled secretory mechanism. Sheep and goats may have a similar alpha-adrenergic control of the sweat gland myoepithelium but only a feeble sweat secretory mechanism. In cattle, an alpha-adrenergic mechanism appears to control sweat secretion, but the control of the myoepithelium is uncertain.


Re-innervation of rat skeleton muscle in the presence of alpha-bungarotoxin.

1. The possible role of acetylcholine (ACh) receptors in controlling neuromuscular synapse formation was studied by blocking the receptors with alpha-bungarotoxin during re-innervationf the rat diaphragm. Anaesthetized and artificially respirated rats were perfused with toxin throughout the 3-day period when most re-innervation was shown to take place (from day 4 to day 6 after a nerve crush). 2. The toxin treatment blocked about 99.9% of both junctional and extrajunctional ACh receptors, thereby eliminating virtually all end-plate potentials. However, a low level of ACh sensitivity returned to the muscle after several hours of washing, and small end-plate potentials were then recorded from the majority of fibres on the side that previously had been denervated. The degree of re-innervation was nearly as great as that seen in control denervated muscles that had not been treated with toxin. 3. The presence of bungarotoxin during re-innervation did not significantly affect either the appearance of newly formed synapses in the light microscope or the amount of transmitter they released during nerve stimulation. 4. Double innervation, which was not seen in normal muscles, was found in about 10-15% of re-innervated fibres in both the untreated and toxin-treated preparations. This suggests that some of the synapses formed during re-innervation may have been made over what previously had been extrajunctional membrane. 5. It is therefore unlikely that the ACh receptor, or at least that part of the receptor to which bungarotoxin binds, plays a direct role in controlling the process of synapse formation in mammalian skeletal muscle...


Ion fluxes during the inhibitory junction potential in the guinea-pig taenia coli.

1. Contribution of different ions to the inhibitory junction potential (i.j.p.) in the guinea-pig taenia coli was studied by measuring the 42K, 24Na and 36Cl fluxes, the membrane resistance and the influence of various external ion concentrations. 2. The membrane resistance, as measured by the electrotonic potential, decreased transiently during the i.j.p. A maximal reduction of the electrotonic potential of about 50% was found at the top of the i.j.p. 3. The i.j.p. amplitude could be reduced by raising the external potassium concentration. Extrapolation of the relationship observed shows that the inhibitory response would be abolished at 115 mM potassium. Similar experiments were made in chloride-free medium, chloride being replaced by isethionate. Amplitude and time course of the response were not different in chloride containing Locke solution and chloride-free medium. 4. The half-times of 42K, 24Na and 36Cl effluxes during rest were 29, 10 and 9 min respectively. The 42K-efflux from the preparation was markedly increased to about three times the resting efflux during field stimulation. In low-chloride solution a similar effect on 42K-efflux was observed during field stimulation. Only a slight increase in the chloride efflux was observed but the sodium efflux was not affected during field stimulation. 5. From the results presented it is concluded that the inhibitory junction potential is caused by a selective increase in potassium permeability of the smooth-muscle cell membrane.


[Metabolic changes in the isolated rat jejunum exposed to continuous light or darkness].

Rats were kept for about seven weeks in continuous light or darkness. The oxygen consumption and glucose consumption by the isolated small intestine were determined. Data were compared to those of control animals kept under a light-dark cycle. Continuous exposure to light resulted in a 21% increase in anaerobic glycolysis. Continuous exposure to darkness increased anaerobic glycolysis by 18 and 12% respectively.


[Intracranial pressure. II. Experimental verification of a mathematical model].

The authors report the results of experiments (performed on the dog in vitro and in vivo) which were designed to verify hypotheses made concerning vascular elasticity and characteristics of CSF resorption, as well as to test the validity of a mathematical model that was described in a previous paper. The authors concluded that the equations of the model account for most of the phenomena satisfactorily, but fail to predict a rebound phenomena which occurs after sudden injections in the cisterna magna. The elasticity coefficient S appears to be constant over a range of 200 mm Hg. On the other hand, the filtration coefficient K depends upon pressure, probably due to morphological changes in the size and shape of the CSF valves. These discrepancies are taken into account in a more general model that is presented in the following paper.


[Changes in the electrical activity of the rabbit proximal colon in vivo by stimulation of the vagus and splanchnic nerves].

1. Using extracellular electrodes placed on the serosa, we recorded the modifications of the electrical activity of the colonic muslce fibers caused by the stimulation of vagal and splanchnic nerve fibers. 2. Vagal stimulation produces two types of junction potentials: excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs). The IJPs are elicited by stimulation of vagal fibers which innervate intramural non-adrenergic inhibitory neurons. 3. The conduction velocity of the nerve impulse along the vagal pre-ganglionic fibers is 1.01 m/sec for excitatory fibers and 0.5. m/sec for inhibitory fibers. 4. Splanchnic fiber stimulation causes EJP disappearance, blocking transmission between preganglionic fibers and intramural excitatory neurons, and a decrease in IJP amplitude that most likely indicates a previous hyperpolarization of the smooth muscle. 5. IJP persistence during splanchnic stimulation proves that sympathetic inhibition does not modify the transmission of the vagal influx onto the non-adrenergic inhibitory neurons of the intramural plexuses. 6. Through a comparative study of proximal and distal colonic innervation, we are able to show that there is a similar organization of both regions, that is a double inhibitory innervation: an adrenergic one of a sympathetic origin, and a non adrenergic one of a parasympathetic origin.


[Intracranial pressure. III. Trial generalized theory].

The authors reported previously an elementary mathematical model of intracranial pressure (ICP) as well as result from an experimental verification of the model. The experimental tests revealed that certain factors had been neglected in the theoretical formation, and the present article offers an expanded version of model which takes into account those factors: changes in the formation of the CSF as a function of ICP; cerebral vasomotricity; cortical and sinusal venous pressures, and variations of the filtration coefficient of the subarachnoidal spaces. A generalized mathematical model of ICP, in the form of four equations, is proposed. The major aspects of both normal and pathological ICP are studied in the light of this model, and are integrated into a generalized theory.


[Elimination of cholesterol and bile acids in bile collected by total fistula in the rat. II. Influence of the pituitary gland].

This paper shows the role of the hypophysis gland on the bile elimination of essential tauroconjugated acids and cholesterol. After transauricular hypophysectomies were performed on rats which were kept under total fistula treatment, we employed an original technique of bile recuperation in rats without contention and observed, over a period of 10 or more days, the choleresis and the composition of eliminated bile.


[Dose of tissue tolerance, dose of tumour sterilisation in continuous and discontinuous irradiation (author's transl)].

In the radiotherapy of cancer, two conditions are necessary:-- 1 degree sterilisation of the tumor; 2 degrees safeguard of surrounding tissues. In discontinuous irradiation, sterilisation depends on the administration of a certain tumour-dose within a suitable period or number of sessions. At the rate of 5 sessions weekly, the following dose-number law may be formulated (ELLIS): DT = 2,500.N0,22. Perfect tolerance of the connective tissue is in fact obtained if the total dose is equal or less than: N.S.D..N0,24.T0,11. The nominal standard dose of ELLIS, is a limiting dose of about 1,800 rads. ORTON and ELLIS have published tables which permit one to obtain, without an index of saturation of the supporting tissue by means of a series of double entry tables corresponding each to a frequency of 1, 2, 3, 4, 5 sessions per week. Each table provides the T.D.F. factor in relation to the number of sessions and the elementary dose. The T.D.F. factor is about 100 whatever the periodicity, and whatever the subdivisions of the dose when ELLIS' equation is satisfied, i.e. when one is at the limit of tolerance. Furthermore, the T.D.F. factor of two parts, of treatment under various regimens may be added together. It is sufficient for the sum to be equal to 100 to ensure full tolerance, which eliminates all difficulty of manipulation of a fractionated formula. The conditions of obtention of continuous irradiation do not permit one to separate the doses of sterilisation and tolerance, as was the case with discontinuous irradiation but, generally speaking, both in continuous and discontinuous administration the shorter the period of treatment the more the sterilising dose exceeds the tolerance dose, whereas with very small tumours, one may obtain tumour sterilisation within the limits of tolerance of the supporting tissues. For very large or radio-resistant tumours, one may have to, in order to obtain sterilisation, exceed more or less the perfect tolerance defined by T.D.F. 100 or its equivalent using ELLIS' equation. The latter is, moreover, only an approximation : the effective tolerance, if one takes into consideration late fibrosis, is very much less than that defined by T.D.F. 100, in particular for high partial dose irradiations. The author insists, after others, on the absolute necessity of taking into consideration the time factor as defined by ELLIS' relationship recalled above. There is no sense in obtaining strict physical dose measurement if one does not also take into consideration the time factor, the biological importance of which is considerable.


[Diagnostic value of ytterbium 169 citrate in cancerology].

Several radio-nuclides are used in Cancerology for their tumoral tropism and, in fact, 67 gallium citrate and 57Co bleomycin almost exclusively. But, these nuclides have some disadvantages, such as we tried to evaluate the interest to 169 ytterbium citrate; this radiolanthanide has already been studied in animals for its affinity for tumoral and normal tissues by HISADA and al. [5]. Our preliminary study has been made on 44 patients bearing different neoplastic diseases. In 8 cases, we have measured the percent radioactivity excreted by urines and stools in 5 days following injection. Scintigraphy of most of the patients has been made at 48 hours, but for several cases of non malignant or malignant pulmonary diseases, a cinetic study allowed us to follow the evolution of the intensity the pathological fixation. The results show: -- a weak urinary and fecal excretion; -- a good scintigraphic contrast from 48 hours; -- an important radioactive fixation in bone metastasis of various origins, in primary and secondary brain and liver tumors; -- an important radioactive fixation in lung cancers and inflammatory diseases however our preliminary cinetic study seems to be a good mean of differential diagnosis. At the cost of a non negligeable irradiation dose of bone, the tumoral fixation can be considered as good and the cinetic studies we intend to develop will perhaps improve the specificity of the diagnosis.


[Exclusive radiotherapy (cobalt teletherapy-radium therapy) in epithelioma of the uterine cervix. 400 cases treated between 1959 and 1969].

The author presents results of 420 cases of epithelioma of the cervix of the uterus treated between 1959 and 1969, using exclusively physical agents such as cobalt therapy and radium therapy. 399 cases are analysed. 9 patients could not be traced and 12 died intercurrently. We have adopted the 1969 U.I.C.C. classification. External irradiation alwyas preceded radium therapy and its importance varied according to the stage: however, doses of 2,000 to 5,000 rads were used at the rate of 1,000 rads weekly for two to five weeks; this was followed by classical radium therapy (Paris method) with colpostat and uterine sound. The number of mgh was consequently reduced and the dose administered was inversely proportional to that of the external irradiation. On the whole, tolerance was good in this type of treatment. Complications were mainly limited to a few minor intestinal disorders; in belated sequelae, these disorders were not more than those usually noted. Results after five years reveal only one death out of 19 for stage T1 lesions. Recoveries are distributed as follows: 72 out of 93 stage T2a lesions (77%), 46 out of 87 stage T2b lesions (53%), 54 out of 131 stage T3a lesions (41%) and 13 out of 46 stage T3b lesions (28%). However, results according to period are better. For the 1967 to 1969 period, results were 92%, 62%, 53% and 30% for stages T2a, T2b, T3a and T3b respectively. Improvement in results could be due to external irradiation. This sterilizes pelvic macroscopic or microscopic extensions and decreases inflammatory phenomena and the volume of the cervix of the uterus. These changes facilitate radium therapy which remains an indispensable arm for sterilizing primary lesions. The author compares his results with those of the literature. He develops arguments for techniques which associate external irradiation and radium therapy in a well defined order. These techniques are particularly important for stages T2b or T3 in which lymph gland lesions are common and where doses of about 5,000 and 6,000 rads are necessary for sterilization. Possibilities of improving future results are analysed. Particular attention should be paid to the lumbo-aortic volume; lymph gland metastasis are frequent here and should be treated continuously with the pelvic volume.


[Influence of inaccuracy of certain parameters on dose distribution in telecobalt therapy (author's transl)].

Progress in dosimetry and in radiobiology together with the evolution of radiation generators led to adopt very elaborated radiotherapy protocols. However, the therapist should have confidence in these protocols on condition that irradiation parameters are strictly respected. For obvious reasons, this is impossible despite the meticulous rules. In this, paper, we therefore intend to study the role of the angle of incidence on the actual distribution of doses; we also study the inaccuracy of certain parameters recorded during preparation for the therapy or shown during successive irradiation courses. In this paper we retain only errors which can be easily quantified. These are errors concerning the irradiation apparatus (source to skin distance, angle of the rays, field dimension) and those due to factors related to the patient treated: contour measurement, entrance point of rays and positional changes of the patient. The different errors can be associated in various ways for a given therapy protocol. For the same reason, an isodose of a given nominal value will have several curves. All these tracings are lined by two curves which we call "superior and inferior envelops": these border the "incertitude area". It can be said that at the end of the treatment, the given isodose lies in this area; it is however impossible to define its form or exact position. A few examples in the text illustrate these results and show the possible practical angles of incidence. If we assume that errors during successive irradiations are distributed at random, a certain compensation is noted and the "areas of incertitude" decrease. But if the errors are constantly on the same side, as is sometimes the case, the dose distribution can be very different from that predicted in the dosimetric protocol.


[Use of photogrammetry for taking body contours in radiotherapy].

A photogrammetric method for taking outline of patients in radiotherapy is described in details. Using only one couple of photographs, this fast and very precise process may restitute a great deal of transversal or longitudinal cross-sections, even after a long time because photographic stocking of information. An automatic numeric lecture of the outline may directly enter a computer for dosimetry.


[Interstitial curietherapy with iridium 192 applied to small cancers of the rectum (author's transl)].

Intracavity irradiation aimed at curing cancers of the rectum mainly calls on contact radiotherapy but also on interstitial curietherapy. Iridium curietherapy has replaced Radium-therapy owing to the better homogeneousness of its' action and precise method of assay. It uses a 2 pronged fork containing 2 Iridium wires which can be very simply placed in position. It is applied on the one hand to the base of the ulcerated tumour, after abraision by contactotherapy and on the other hand as a method of prophylactic irradiation after exeresis of a malignant or degenerated polyp where the scar is badly adapted to contacto-therapy.


[Breast xeroradiography (author's transl)].

Breast xeroradiography is a new radiological technique based upon the electrostatic and not the photographic properties of silver bromide. We have used it particularly with reference to breast disorders in order to compare it to traditional procedures and to seek the best conditions to obtain the most informative picture by comparing the radiation emitted by a tungsten anode with the radiation emitted by a molybdenum anode with molybdenum or aluminium filtration. We concluded the xeroradiography was of value in breast problems in the following instances: 1. For certain types of microcalcification. 2. For the precise study of the relation of the breast to the chest wall. 3. For breast with a uniform high density on conventional films (young organ, fibro-glandular hyperplasia, after high-dosage irradiation). 4. In the study of deep seated carcinomas or those in the sub-mammary fold. 5. In studying the axilla where the ribs, muscles and nodes are seen together on the same film. Comparative study of xeroradiography using either a tungsten or molybdenum anode was markedly in favour of the latter under all the circumstances mentioned above.


[Mammary echothermographic comparisons (author's transl)].

This attempt at comparison between the absorption and thermogenesis of breast tumour tissue is currently being continued using a larger group of patients and complemented by measurement of tumour thermogenesis in situ and of the acoustic properties of operative specimens. Such studies define the contributions of thermographic and ultrasonic findings in diagnosis, prognosis and indications for biopsy and treatment, by their integration and combination alongside the data obtained by palpation/inspection and radiological, cytological and histological findings.


[Spontaneous reversal of portal flow in cirrhosis. Angiographic study of 15 cases (author's transl)].

Spontaneous reversal of intra-hepatic portal flow in cirrhoses appears to be best demonstrated by arteriography, which shows a direct sign, i.e. retrograde opacification of intra-hepatic portal branches during selective hepate arteriography, and an indirect sign, i.e. the appearance of functional amputation of these same portal branches at the time of superior mesenteric venous return. Reversal of portal flow is sometimes complete (5 out of 15 cases), the flow being entirely away from the liver and sometimes incomplete (10 out of 15 cases), limited to the interior of the liver, portal flow then being bidirectional. Reflux of arterial blood in the intra-hepatic portal branches via the development of intra-hepatic arterioportal communications appears to be the determining factor in the reversal of portal flow in cirrhosis. The degree of portal flow away from the liver seems to depend essentially upon the extent of development of porto-caval anastomoses. Certain features suggest that there is a relationship between the development of the hepatic arterial circulation and that of the porto-caval anastomoses. These two elements which determine the degree of portl hypertension may mutually influence each other. This hypothesis is interesting in the context of understanding the haemodynamic abnormalities of advanced cirrhosis.


[Radiological aspects of renal metastases. Apropos of 9 cases].

Renal metastases are tumours which are not rare and which may reveal a primary neoplasm previously undiagnosed. The primary tumours identified in the nine cases reported were six squamous cell carcinomas of the bronchus, one carcinoma of the breast, one carcinoma of the thyroid and one meningioblastoma. Signs at intravenous pyelography are variable, with a marked predominance of appearances of infiltration of the excretory passages by the renal mass, with or without direct involvement of the excretory passages. Angiographic signs appear to be related to the nature of the primary tumour with frank hypovascularisation in the metastases of bronchial tumours and hypervascularisation in those of carcinoma of the thyroid and meningioblastoma. Radiological diagnosis is difficult given the absence of specificity of the urological and anglographic signs. Even histologically the diagnosis may be difficult, particularly in the case of primary bronchial tumours-this being the commonest possibility.


[Measurement of flow in the Cordis-Hakin type ventricular shunt valve, used in the surveillance of hydrocephalic patients with shunts. An experimental study (author's transl)].

Using isotopes, Benabib et al. were able, in 1970 and following the work of Descuns et al., to evaluate the function of a ventricular shunt system be measuring the flow passing through it. The experimental study carried out confirmed the applicability of the method described by Benabib et al. to the Cordis-Hakim valve after substitution of the 131I used by those authors by 99mTc O4. Measurement of flow is valid only if true flow lies between 0.085 ml/mn and 1.7 ml/mn. Although with flow rates of less than 0.07 ml/mn the values obtained are overestimates, the distinction between no flow and slight flow remains definite.


Herpes zoster in general practice.

Eighty-seven patients with the clinical diagnosis of herpes zoster were seen during a one-year period in eight general practices in Glasgow, the rate per 1,000 practice population being approximately 2.4. Of these, 78 (90 per cent) had serological evidence of active infection with herpes zoster. The anatomical location of the skin eruption was most common in the areas of the fifth cranial nerve, middle and lower trunk and thigh. A possible reactivating agent (trauma four, steroids two, irradiation one) was found in only seven patients. The illness as assessed by systemic upset and dissemination of lesions was generally not severe. Post-herpetic neuralgia was the most troublesome complication, found in 44 per cent of 64 patients revisisted 3-18 months after the acute illness.


Hand, foot and mouth disease--1973.

Nine cases of hand, foot and mouth disease were found in a small area within a month. The condition is benign, commonest in small children, and the infectivity is low. It is suggested a fuller investigation be considered in 1976.


[Osseous scurvy in an 11-month-old infant. Radiological course].

The authors report the case a 11-month-old baby girl admitted by the "Mother and Child Welfare" doctor. On admission, she was very hypotrophic, febrile and pale. Furthermore, she had anaemia complicated with painful invalidating oedema of both thighs. X-ray film show moderate lesions of the metaphysis, but very rapidly, there was a hugh bilateral sub-periosteal hematoma. They insist on the value of periosteal hematoma as a characteristic sign of scurvy. This was later confirmed by laboratory investigations and by the finding of urinary infection due to bilateral reflex on cystography and to right uretero-hydronephrosis on I.V.P. This case is singular because it associates three findings: severe vitamin deficiency by dietetic error due to modern industrial alimentation and a major urinary tract malformation with refractory urinary tract infection.


A year's study of drug prescribing in general practice using computer-assisted records.

A year's drug prescribing by five family doctors working in a new town is reviewed. The records were computerised and some of the problems which this involved are mentioned.The range of different preparations which were used over the year was high but 76 per cent of prescriptions were accounted for by 117 preparations; 30 per cent of total prescribing was for antibiotics and psychotropic drugs. The lessons to be learned from ;self-audit' have been shown and areas for future study are discussed.


Prescribing psychotropic drugs for children.

The prescribing of psychotropic drugs was studied in a Scottish general practice of five doctors and 8,300 patients; one third of the patients were aged 12 years or less. In 1971, 336 prescriptions for psychotropic drugs were issued to 172 children and 2,583 to the adults. Most children were given only one prescription, but some needed up to ten in one year.The drugs consisted of sedatives (43 per cent), tranquillisers (41 per cent), and hypnotics (17 per cent). Most were given for behaviour disorders and enuresis. The analysis of drugs given by each doctor showed that one had given about one third of the total. This demonstration of comparative over-prescribing was useful in discussing self-audit.


[Osteopathies associated with sickle cell disease (author's transl)].

1. In all patients of African descent, and above all in all children of three months and older, the attention of the radiologist should be directed to the possibility of sickle cell anaemia in the presence of bone lesions with the following characteristics:--either diffuse pseudo-tumoural, signifying erythroblastosis secondary to anaemia;--or pseudo-osteitic, signifying thrombosis secondary to sickling. 2. These appearances from part of a rich and misleading pathological spectrum, in particular in rheumatology and pulmonary medicine, and even surgery. 3. The presumptive radiological diagnosis may be complemented by electrophoresis of haemoglobin which, alone, makes confirmation of the diagnosis possible.


Lead in potatoes.

There are specific environments where potatoes contain much larger amounts of lead than is generally realised. Nevertheless, if we accept the hypothesis that human adults are only likely to be harmed if they absorb more than 100 micrograms of lead daily for extended periods(10) then only in rare instances are they apt to be adversely affected by eating potatoes. Medical data suggest that where children are involved the acceptable amounts of lead are significantly less. However, where potatoes do show evidence of contamination by virtue of their high lead content, the possibility of more general contamination should be investigated. The intake of lead from potatoes, if supplemented by lead provided from other foodstuffs, from air, and possibly from water, can well reach unacceptable amounts.Patterson's(12) claim that most people in industrialised countries are suffering from a chronic lead insult, does seem justified but, because of the remarkable ability of humans to adapt to some conditions, but how much this insult constitutes a menace to heath must be dealt with by medical men.


Marriage guidance counselling in a group practice.

This paper describes the work of a marriage guidance cousellor in a group-practice centre. The considerable advantages to patient, doctor, and counsellor of her close association with the primary medical care team are discussed.


Acute sore throat--diagnosis and treatment in general practice.

This study tested how general practitioners diagnose streptococcal infection on clinical grounds alone, in patients who presented with sore throats.Four hundred and fifty-two patients were admitted to the study. A clinical diagnosis, prognosis and follow-up was completed in each case and the clinical assessment was checked by throat swabbing at first contact and a week later.The doctors were inaccurate in predicting streptococcal infection, but better than might be expected if prediction were a matter of pure guesswork. Colds and influenza implied negative prediction, tonsillitis a positive prediction, and pharyngitis was doubtful.In this series negative prediction for pharyngitis was 85.2 per cent and positive prediction 31.5 per cent accurate. The equivalent figures for tonsillitis were 61.5 per cent and 38.9 per cent respectively. There was a general tendency to overpredict streptococcal infection which was most marked in acute follicular tonsillitis, but this led to few false negatives. The tendency to overpredict streptococci was most marked when the patient was an adolescent female.There were differences between the urban and rural patterns. During the same period, influenza (and similar illnesses) was recorded less often in the country, whereas urban practitioners were more likely to predict streptococcal infection. Rural practitioners were more accurate in prediction because they were less prone to implicate streptococcal infection than their urban colleagues; there was a higher proportion of cases with proven streptococcal infection in the town and there is a disproportionately high number of adolescent females among the urban patients.


Using a 'Portakabin' to gain space in a general practice.

The problem of extra space needed for a general practice has been temporarily solved by the use of a ;Portakabin'. While orthodox building methods are so frustratingly expensive, we must consider unconventional methods which allow us to gain space relatively quickly.


The use of stencilled labels in general practice.

A system of using wet (ink) stencils to prepare self-adhesive labels showing the patient's name and address is described. Several uses are illustrated in general practice and other systems are considered.


[Management of renal trauma in the child (author's transl)].

Intravenous pyelography remains the basic examination in the study of the child with lumbar trauma. This examination has its limits, however, and renal arteriography may be necessary in a fair number of cases. Provided that adequate reflection is given and the appropriate moment chosen, it is well tolerated and provides all the necessary information.


The use of name and address spirit masters in general practice.

The use of an address master system in a general practice can save the doctors and secretarial staff a significant amount of time. A spirit master system (e.g. ;Scriptomaster' sets) best suits the requirements of general practice. Uses include labelling documents, request forms, prescriptions, envelopes and compiling lists of patients.


The findings reported in patients undergoing excretory urography for recurrent urinary tract infection.

There was little difference between the proportion of lesions found by excretion urography in patients with recurrent urinary tract infections referred by general practitioners or hospital staff, or between Horton General Hospital which is a district general hospital, and the United Oxford Hospitals, which is a teaching group. Many patients with urinary tract infections may be saved an unnecessary visit to the hospital consultant if this is first investigated by the general practitioner.About one fifth of all patients had significant lesions shown by excretory urography which suggests that the investigation is worthwhile in patients with recurrent urinary tract infections.


Lessons from bad general practice.

The paucity of resources for general practice correlates well with high losses through emigration and questions the expensive over-production of doctors now being undertaken.The variable quality of community care and the absence of a structure yet providing real planning or capital, leads to the uneconomic abuse of hospital facilities and to an excessive emphasis on institutionalisation.Medicine is becoming depersonalised because unrealistic expectations lead to an overloading of the service. Simultaneously we allocate a low priority to education in the use of the service, have little training in the sociological aspects of medical care, and even less in how best to use the skills of our non-medical professional colleagues.


Radio-paging services.

This report is a description of the development and organisation of an area radio paging service in Cambridge and its application to doctors and para-medical staff working in various hospitals and in the community. It reviews the first five years of operation.Personal selective radio paging has some fundamental advantages over the car radio-telephone as a means of communication. Currently, the service operates only in the Cambridge area, but it is planned to extend this to cover the new county of Cambridgeshire by February 1975, and, at the same time, to introduce speech.


The effect of weather on some infectious diseases.

For several years the Royal College of General Practitioners has been collecting data supplied by local doctors throughout Britain on some infectious diseases seen in their practices. We describe a method of computerisation of this information and statistical analyses. We are investigating the influence of external factors such as climate on the infectiousness of some diseases. A model is fitted involving a non homogeneous two-state Markov chain whose transition probabilities are governed by the explanatory data.


Reported morbidity and the weather.

Some observations have been made about the influence of the weather on the use of the general-practitioner service. It is difficult to disentangle the biological and behavioural components of these findings, but in general extremes of weather-low temperatures and sunshine in winter and high temperatures and sunshine in summer-appeared to increase the numbers of reported episodes of respiratory illness.


Exposure of girls to oestrogens during fetal development. Report of a survey of maternal records.

In a two-partner practice with 5,000 patients where oestrogens had never been prescribed during pregnancy, it was found on examining the records, that at least eight girls had been exposed to oestrogens in utero, two of them to stilboestrol. Three of them have since been examined with negative results. In a quarter of cases no information was available from the records.


The vulnerable child.

There is enough evidence from epidemiological studies of respiratory disease in children and young adults to justify testing various strategies for the identification of those children who are particularly vulnerable to respiratory disease. Such studies should be coupled with anti-smoking programmes carried out by those involved in the health education of schoolchildren and adults. The effects of this selective approach to the prevention or control of respiratory disease would require rigorous evaluation.


Antibiotics in the treatment of tonsillitis.

Tonsillitis was studied in 317 patients over two years. A short course of antibiotics was found to be highly effective in clearing streptococci from the throat, but it was questionable whether the clearance shown represented eradication. It is suggested that the duration of treatment should be on a selective basis, using a ten-day, or short antibiotic course, according to circumstances. Withholding antibiotics altogether is not considered advisable. I could not differentiate between streptococcal and presumed viral tonsillitis on clinical grounds. The resulting possible policies of treatment are discussed. I suggest giving all cases of tonsillitis antibiotics at the time of presentation.


Handling information in general practice--using feature cards with computers.

A two-tier system of handling information has been developed for use in general practice. Punched feature cards, with the conventional patients' record cards are used for the handling of primary data in the doctor's surgery. At the same time the feature cards provide an input to the computer using a feature card reader, converter, and paper-tape punch. This is especially useful where information has to be collected together centrally, for more advanced statistical analysis and where multiple searches of individual feature cards are required.


Using an age-sex register.

A study of practices using an age-sex register suggested that more use could be made of registers, especially in preventive medicine. Difficulties in creating and maintaining the register, as well as analysing it, discourage many practices. Those who make full use of their register obtain great benefit from it.


How general practitioners assess risks in using new drugs.

;Situational' risk is an important determinant in the adoption of new pharmaceuticals. Not specifically the scientific risk of using the drug, but rather the risk the doctor perceives through his previous experience, both with similar treatments and with factors associated with the innovation such as its sponsor and mode of action. With this information the doctor determines to what degree further validation is required in order to allay any fears. The extent and complexity of this additional reassurance will thus determine how long is required before adoption and to what extent additional sources of information should be consulted.


Monitoring and evaluating the physiological changes in the horse with acute abdominal disease.

Initial examination and therapy, and the avoidance of maltreatment are emphasized. Gastric decompression is of prime importance, after which no compound should be administered via stomach tube. Where large amounts of high starch grains are fed, primary acute gastric dilatation must be differentiated from that secondary to small bowel dilatation, by immediate gastric intubation and irrigation of the cardia with lidocaine. If cessation of pain and improvement of peristalsis and general attitude follow, the former state may be assumed. If pain persists and peristalsis does not improve markedly, one should assume small bowel displacement. Rectal examination is helpful in initial evaluation: impactions, inguinal herniation and ileocaecal intussusception may be diagnosed and small bowel displacement suspected. Palpation of one or more distended loops of bowel in the ventral middle third of the abdomen indicates small bowel displacement or ileus and flaccid distension. Distinction by rectal palpation alone is difficult. Palpation of the gas-distended apex of the caecum in the middle third of the abdomen is virtually pathognomonic for 180 degrees rotation of the large bowel. Abdominal paracentesis yielding true sanguineous effusion indicates a necrotizing segment of the bowel. If negative, such a segment is absent, or there is an infarcted segment, not yet damaged to the point of leaching whole blood, or the necrotizing segment is outside the peritoneal cavity, i.e., in the thorax, intussuscepted into the caecum, or herniated into the inguinal canal. Recurrent colics frequently may be due to verminous arteritis but the relationship to diet should be investigated. Recurrent colics after grain ingestion with occult blood in the faeces may be due to ulcers; such cases respond well to grain withdrawal. The advantages and disadvantages of phenothiazine-derived tranquillizers are discussed. They are contra-indicated if there is any evidence of circulating volume insufficiency but are benefical in many instances through improved peripheral perfusion of organs provided circulating volume is adequate, i.e., early in acute abdominal disease prior to development of circulatory insufficiency. They should not be administered if immediate surgery is contemplated because of hypotensive effects. The administration of oral antibiotics (Neomycin) early in the course of the disease is encouraged. This is contra-indicated if the horse is already toxic, when it should receive parenteral antibiotics, preferably chloromycetin. Tetracyclines may predispose to the later development of salmonella diarrhoea. Absolute analgesia should be provided; our preference is the magnesium sulphate-chloral hydrate solutions. Administration of mineral oil is desirable in initiation of peristalsis, depression of Gram-negative overgrowth and softening of impactioning obstructions but nothing should be administered per os if the stomach has required decompression.


Surgical techniques in equine colic.

Emergency equine abdominal surgery is easiest and most efficiently carried out with a team of surgeons. The surgical site should be as protected as possible by the use of sterile drapes and wound protectors. A ventral midline laparotomy incision has been found to be the most convenient approach to most equine intestinal obstructions. A standing laparotomy through the left paralumbar fossa gives adequate exposure for exploration of the abdomen and is, therefore, useful as a diagnostic tool. Horses tolerate having both ventral midline and left paralumbar laparotomy incisions well. If the cause of the intestinal obstruction is not readily apparent upon opening the abdominal cavity, a thorough systematic exploration of the abdominal cavity is necessary. If the problem cannot be found with the bowel in situ, intestine must be exteriorized for examination. The decision as to the extent of adequate bowel resection often depends on a subjective assessment of bowel function. In equivocal cases, the surgeon should choose to resect some normal bowel rather than taking a chance on leaving compromised bowel in place. Incarcerations are frequent causes of small intestinal obstructions. The small intestine may become incarcerated in the epiploic foramen, the inguinal canal or in an umbilical hernia. Thromboembolic compromise to intestinal vessels results in the longest lengths of embarrassed bowel requiring resection. Impactions are the most common obstructions associated with the caecum. Large colon torsions of 270 degrees or less may be corrected by surgical manipulation; with 360 degrees torsions of the large colon, however, vascular compromise is usually sufficient to devitalize this organ. Enterotomy of the large colon allows retrieval of most enteroliths from its lumen. Enterotomy of the right dorsal colon is also useful for removal of foreign bodies which cause obstruction of the most proximal portion of the small colon. In our Clinic a two-layer end to end anastomosis is usually utilized. Recently introduced automated stapling and ligating instruments have been useful in decreasing surgical time. Antibiotics, usually furacin and sodium or potassium penicillin in 2 litres of Normasol-R, are placed in the peritoneal cavity before closure of the abdomen. A Penrose drain is commonly placed into the abdominal cavity to provide drainage of the peritoneal cavity after surgery. The peritoneum is sutured with No 0 chromic gut in a simple continuous pattern. A second Penrose drain may be placed between peritoneum and ventral body wall, with its ends retracted through stab incisions in the skin. The linea alba is closed with simple interrupted sutures of stainless steel wire or No. 3 chromic gut. Employing the above described principles and techniques has increased the success of abdominal surgery in our Clinic.


Post-operative management of equine abdominal patients.

Adequate post-operative management of equine abdominal patients is as necessary to patient survival as the most heroic corrective surgery. Post-operative management must begin during the anaesthesia recovery phase to insure adequate oxygen supply, ventilation, and minimize any abdominal discomfort. The animal's physiological status must be constantly monitored to detect and determine the degree of abnormalities concerning serum electrolytes, fluid balance, and acid-base abnormalities. The most commonly observed serum electrolyte imbalance is hypokalaemia. Replacement potassium is usually supplied intravenously. If the dificit is slight, oral replacement may be possible. Fluid balance is usually maintained via intravenous fluid therapy as determined by monitoring PCV and plasma protein. Metabolic acidosis is treated with 5 percent sodium bicarbonate administered intravenously. Broad spectrum antibiotics are usually given intravenously but may be administered intra-peritoneally. To facilitate the intravenous therapy, an indwelling silastic catheter is often employed to minimize jugular thrombosis.


Dietary value of cubes in equine nutrition.

The revised NRC's Nutrient Requirements of Horses is changing the outlook on equine nutrition, dominated for so long by the traditional belief in oats. This has lead to the need for properly balanced diets, in the compounding of which dietary cubes offer the distinct advantage of providing a standardized diet of constant quality in keeping with modern knowledge. Additional factors are: longer storage, freedom from dust, palatability, refractoriness to mould infection, and facilitation of routine feeding. Cube size and hardness are important considerations for the manufacturer. Horses appear to favour smaller-sized cubes, but on the whole preferences for size and hardness appear to be equivocal. The nutritional status of four commercial brands of horse feed marketed in South Africa has been analyzed and compared to commonly used raw feedstuffs. The results of feeding cubes have been assessed by means of a questionnaire. There appears to be a need for more knowledge concerning equine nutrition on the part of trainers, as well as for more specialized advisory services. The establishment of training centres has been suggested.


Intestinal surgery in the foal.

Intestinal surgery in the foal is seldom necessary but some conditions in which it is essential are well recognized. The foal is a good surgical subject but success depends mainly on operating promptly before irreversible degenerative changes take place. Exploratory laparatomy is recommended whenever mechanical obstruction is suspected. Indications fall broadly into two main categories: 1. Cases arising from congenital defects. These form a miscellaneous group and present considerable difficulties in diagnosis and effective treatment. 2. Cases related to acute onset of obstruction, mainly due to volvulus or torsion. By far the most important condition in this category is volvulus of the ileum close to the ileocaecal valve. Aetiological factors are discussed, and the value of resection of affected small intestine and creation of a new jejuno-caecal opening is indicated. It is suggested that with improvement of such techniques it will be possible to save a higher proportion of foals suffering from mechanical intestinal obstruction.


Differential diagnosis of diarrhoea in horses over six months of age.

Pertinent questions regarding the history of a horse with diarrhoea are listed, as are diagnostic procedures that might be included in a complete clinical work-up. For purposes of discussion, diarrhoea is regarded as "acute" or "chronic" wherein the former concerns cases where the features of the disease are severe with progressive electrolyte imbalance, dehydration, toxaemia, or other life-threatening manifestations and the latter refers to cases that have been prolonged for a month or more. Patterns of disease, including results of diagnostic techniques, are stressed. In the "acute" category, salmonellosis, haemorrhagic and oedematous colon (Colitis X), acute peritonitis, and Corynebacterium equi infection are discussed in some detail. In the "chronic" group, strongyle larval migrans, granulomatous enteritis, chronic liver disease, Corynebacterium equi infection and chronic salmonellosis are emphasized.


Pathological infection of thoroughbred horses with Gastrodiscus aegyptiacus.

Contrary to common belief, Gastrodiscus aegyptiacus can be pathogenic to horses. History of cases of a particular stud, necropsy findings, diagnosis, and successful treatment with hexachlorophene and with dichlorvos are recorded. The presence of eggs can be established by a special flotation technique.


The pathogenesis and control of strongyle infection in the horse.

The migratory route of infective Strongylus vulgaris larvae was determined: penetration of small and large intestine into the lumina of submucosal arteries, migration up the arterial tree, reaching the cranial mesenteric site by three weeks, where the larvae develop to the mature 4th stage. After 3-4 months they exsheath and the young adults migrate down the arteries towards the intestines, to the limit of arterial narrowing, from where they rupture from nodules into the lumen of the intestine. The prepatent period is about 6 months. The clinical syndrome was similar to, but less severe than that recorded in the literature. The most significant haematological changes were an early, sharp rise in WBC, increased neutrophil:lymphocyte ratio, and eosinophilia. Marked, progressive increase of total serum proteins as result of betaglobulins occurred. The rate of albumin catabolism was higher in infected horses and red cell survival was reduced. In field studies, it was shown that foals turned out to grass in spring can be infected both by overwintering larvae and by their untreated dams, the latter being by far the more important source of infection.


Causes of colic and types requiring surgical intervention.

The migration of strongyle larvae is the most common or basic underlying cause of colic in the horse. Disease conditions producing symptoms of colic occur in all sections of the intestinal tract and consist of impactions, torsions, herniations and foreign bodies. Colic also occurs as a result of pre- and post-partum diseases such as torsion of the uterus, haemorrhage, rupture and inversion of the uterus. In general, lesions resulting in circulatory obstruction are the types requiring surgical intervention. There are six general types of small intestine obstruction that lend themselves to surgical treatment; namely, volvulus, herniations, intussusceptions, stenosis of the lumen of the bowel by external bands or by foreign bodies and chronic inflammatory lesions. The large intestine is not subject to the variety of obstructive lesions found in the small intestine. Impactions count for a large percentage of the obstructions seen. A standing laparotomy for diagnostic purposes may be indicated. Small colon impactions are readily treated by standing laparotomy. Enteroliths are of very common occurrence in some areas of the country; they often result in rupture of the colon. Torsions of the colon produce septic shock very rapidly. The left dorsal colon moving medially or laterally and ventrally initiates the torsion. Clockwise rotation is most common. Massive intravenous therapy is needed to maintain hydration. Ventral midline laparotomy gives best access. Surgery must be performed very early to avoid massive tissue necrosis. Survival rate is 30 percent or less. The small colon is also capable of rotation and volvulus, and of strangulation in the umbilical or inguinal ring.


Quantum chemical studies of meperidine and prodine.

Extensive quantum chemical calculations have been made of the electronic distribution and conformational behavior of meperidine and desmethyl-, (+)-alpha, and (+)-beta-prodine using PCILO, a semiempirical molecular orbital method. For this series of opiates, a phenyl equatorial conformation was preferred over a phenyl axial one, with the equatorial conformer most favored in the most potent compounds. Using the low-energy equatorial conformer obtained for each compound, together with calculated net atomic charges, their observed potency variation could successfully be explained. From the results, these compounds appear to act at the morphine receptor with an identical piperidine rather than phenyl ring site.


Primary and beta-secondary deuterium isotope effects in N-deethylation reactions.

Lidocaine (1), labeled specifically with deuterium in the alpha-methylene (lidocaine-d4,2) and beta-methyl (lidocaine-d6,3) carbon atoms of the terminal amino group, was used to probe the mechanism of oxidative N-deethylation by rat liver microsomes. The reaction rates were determined by measuring the formation of acetaldehyde colorimetrically. This general assay for oxidative N-deethylation reactions has the advantages of being rapid, producing a relatively stable colored derivative and being linear over the range of 0.25-4 mug of acetaldehyde formed per milliliter of incubate. Deuterium substitution at the methylene carbon atoms, the presumed site of initial oxygen insertion, revealed a kH/kD = 1.49 +/- 0.11 and a KmD/KmH = 1.23. Deuterium substitution on the terminal methyl groups showed a kH/kD = 1.52 +/- 0.10 and a KmD/KmH = 0.92. The results are explained in terms of both primary and secondary isotope effects on a possible rate-determining step in the N-deethylation sequence.


Synthesis of thebaine and oripavine from codeine and morphine.

A practical synthesis of thebaine and oripavine has been developed from codeine and morphine, respectively. Attempts to use a codeinone intermediate gave poor yields; however, methylation of the potassium salt of codeine to give codeine methyl ether followed by oxidation with gamma-MnO2 gave thebaine in 67% yield from codeine. Similarly, the potassium salt of the di-O-anion of morphine was selectively alkylated to give morphine 6-methyl ether (heterocodeine) in better than 90% yield. Hetercodeine was then acetylated and oxidized to oripavine 3-acetate which was hydrolyzed to give oripavine in 73% yield from morphine.


Cardiovascular activity of aromatic guanidine compounds.

A series of aromatic guanidines and several 1-phenylbiguanides was prepared and tested for cardiovascular (CV) effects in anesthetized dogs measuring heart rate, blood pressure, carotid artery blood flow, and myocardial force changes. The predominant CV effect at minimally effective dose was vasoconstriction unassociated with cardiac stimulation. The structure-activity relationships of the compounds were discussed comparing their structural similarities to the beta-phenylethylamines. The most potent members of the series were phenylguanidines substituted in the 3 and 4 positions on the aromatic nucleus with hydroxy or chloro groups. Preliminary mechanism studies indicated that the 3,4-dihydroxyphenylguanidines act at least partially by a direct alpha-adrenergic mechanism


Synthesis of deuterium-labeled analogs of cyclophosphamide and its metabolites.

Convenient syntheses are described of d4 analogs of cyclophosphamide and some of its metabolites, potential standards for the quantitative analysis of the drug and its metabolites in human body fluids by stable isotope dilution-mass spectrometry. Base-catalyzed H-D exchange on N-nitrosobis(2-hydroxyethyl)amine gave N-nitrosobis(1,1-dideuterio-2-hydroxyethyl)amine from which bis(2-chloro-1,1-dideuterioethyl)amine (nor-HN2-d4) was readily obtained. Established synthetic routes were then used to convert nor-HN2-d4 into d4 analogs of cyclophosphamide [2-[bis(2-chlorethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide], 4-ketocyclophosphamide [2[BIS(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorin-4-one 2-oxide], and carboxyphosphamide [2-carboxyethyl N-N-bis(2-chloroethyl)phosphorodiamidate], and these analogs were used in a preliminary investigation into the quantitation of the appropriate components in human plasma and urine. Also prepared were d4 analogs of phosphoramide mustard [N,N-bis(2-chloroethyl)phosphorodiamidic acid (cyclohexylammonium salt)] and 3-(2-chloroethyl)oxazolidone and the methyl and trideuteriomethyl esters of phosphoramide mustard.


Synthesis and biological properties of some novel heterocyclic homoprostanoids.

In the search for prostaglandin-like structures capable of exerting specific and desirable biological properties, a variety of simple heterocyclic homoprostanoidal derivatives was synthesized from readily available stearic acid derivatives. Compounds 5b and 5e were found to be more than 100 times as potent as PGE1 and PGE2 in a tracheal chain bioassay and, like 6, 9, and 12, inhibited PGE2-induced diarrhea. Derivatives 6 and 7a showed significant PG-synthetase inhibitor activity.


Synthesis and antitumor activity of 6-trifluoromethylcyclophosphamide and related compounds.

In an attempt to increase the combined toxicity of the metabolic end-products [acrolein (4) and phosphoramide mustard (3)] from cyclophosphamide (1), the analog 2-[bis(2-chloroethyl)amino]tetrahydro-6-trifluoromethyl-2H-1,3,2-oxazaphosphorine 2-oxide (2, 6-trifluoromethylcyclophosphamide) was synthesized and its metabolism and antitumor activity studied. Following metabolism of 2 by rat liver microsomes the predicted formation of 4,4,4-trifluorocrotonaldehyde (5) was confirmed by isolation and identification, by mass spectrometry, of its dinitrophenylhydrazone. The therapeutic indices (LD50-/ID90) for 2 against the ADJ/PC6 mouse tumor and the Walker 256 tumor in the rat were 28.6 and 7.7, respectively, and were lower than the corresponding values for 1 (91.8 and 33.2, respectively) although the toxicities toward Walker cells in a bioassay system of 1 and 2 following microsomal metabolism were similar. In order to study the toxicities of 4 and 5 released under drug metabolizing conditions independently of the production of a toxic mustard the analogs 18 [2-(diethylamino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide] and 6 [2-(diethylamino)tetrahydro-6-trifluoromethyl-2H-1,3,2-oxazaphosphorine 2-oxide] were also synthesized. The release of 5 from 6 following metabolism was confirmed and shown by use of the bioassay system to be an event of similar toxicity to release of 4 from 18; in vivo, however, 6 (LD50 330 mg/kg) was more toxic to mice than 18 (LD50 greater than 500 mg/kg).


Potential antitumor agents. 16.4'-(Acridin-9-ylamino)methanesulfonanilides.

The structure-antileukemic activity (L1210) relationships for sulfonanilide ring-substituted variants of 4'-(acridin-9-ylamino)methanesulfonanilides have been investigated. Electron-donor substituents are necessary for antileukemic activity and it is suggested that high electron density at the 6' position is associated with high activity. A 3'-OCH3 function markedly increases (2-8-fold) potency with a variety of acceptable acridine ring substituents. Further variants with hydrophobic acridine 3-substituents have been shown to be more active than expected on the basis of overall molecular hydrophilic-lipophilic balance. There is a size limit to 3-substituents which may acceptably be as large as an iodine atom but should be smaller than an isoporpyl function.


3-Arylquinolizidines, potential antidepressant agents.

The synthesis, structure elucidation, and pharmacological evaluation of some 3-arylquinolizidines as semirigid phenethylamines are described. Many of the derivatives posses antidepressant activity. Some anticonvulsant effects are noted.


Antiarrhythmics. N-(aminoalkylene)trifluoroethoxybenzamides and N-(aminoalkylene)trifluoroethoxynaphthamides.

Benzamides and naphthamides characterized by one or more 2,2,2-trifluoroethoxy ring substituents have been prepared and evaluated as antiarrhythmic agents in mice. Structure-action studies reveal that antiarrhythmic activity is highly dependent upon the number and position of 2,2,2-trifluoroethoxy groups. The most potent compounds are derived from 2,5-bis(2,2,2-trifluoroethoxy)benzamide, and, within this group, wide variation of the amide side chain is possible without adversely affecting the antiarrhythmic activity.


2-(3,4-Dichloroanilino)quinolizinium bromide, a unique antispasmodic, antisecretory, and antiulcerogenic agent.

2-(3,4-Dichloroanilino)quinolizinium bromide (3) was prepared by reaction of 2-bromoquinolizinium bromide with 3,4-dichloroaniline in ethanol. This compound possesses unique antispasmodic, antisecretory, and antiulcerogenic properties.


Structure-activity relationships in reactivators of organophosphorus-inhibited acetylcholinesterase. 10. Hydroxyiminomethylarylethenylpyridine methiodides.

The synthesis of styrylpyridine methiodides where a hydrogen of the pyridyl moiety was replaced by the hydroxyiminomethyl group produced highly effective inhibitors of acetylcholinesterase. As starting materials 4-methylpyridine-2-aldoxime and 2-methylpyridine-4-aldoxime methiodides were prepared which, together with 4-imidazolylethenyl-pyridine-2-aldoxime methiodide, were the only substances for which some activity as reactivators of phosphorylated electric eel cholinesterase in vitro could also be found.


Application of the carbonic anhydrase inhibitory effect of furosemide to the study of furosemide release from two of its diuretic derivatives.

Bovine carbonic anhydrase B (CA) inhibitory effect of furosemide was established in two pH values at 26 degress. FFBu [N-furfuryl-4-chloro-5-(butoxymethylsulfamoyl)anthranilic acid] and FFMe [N-furfuryl-4-chloro-5-(methoxy-methylsulfamoyl)anthranilic acid], two of its alkoxymethyl derivatives, did not exert any CA inhibitory effect at those conditions but were found to inhibit the CA activity after their hydrolysis, which yielded the furosemide molecule. The CA inhibitory effect of furosemide was utilized for determining the kinetic rate constants for the hydrolysis of FFBu and FFMe at various pH and temperature levels. The hydrolysis rate constants of FFBu and FFMe were pH-independent in the pH range tested, and the temperature dependence for FFBu yielded an activation energy of 18 kcal/mol. It is pointed out that the hydrolysis rates of FFBu may be important for the explanation of its possible delayed diuretic effect.


Synthesis and antiinflammatory activity of some 2-heteroaryl-alpha-methyl-5-benzoxazoleacetic acids.

The syntheses of eight of the title compounds are described. The compounds possessed activity comparable with that of the previously tested 2-substituted phenyl analogs in the carrageenan-induced rat paw edema test.


A lapachol derivative active against mouse lymphocytic leukemia P-388.

Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] and its analogs [2-(3,7-dimethyl-2,6-octadienyl)-3-hydroxy-1,4-naphthoquinone and 2-(3,3-dibromo-2-propenyl)-3-hydroxy-1,4-naphthoquinone] have been described, among almost a hundred synthesized analogs, as active against rat tumor Walker 256 carcinosarcoma. The acetylglucosylation of lapachol results in a compound which extends lapachol activity becoming effective against mouse lymphocytic leukemia P-388. When mice inoculated with 10(6) leukemic cells were treated with the drug during 9 days, their life span increased 80% over the control animals. Identification spectral data (uv, ir, 1H NMR, and MS) of the compound obtained by synthesis are given.


Methyl 5(6)-phenylsulfinyl-2-benzimidazolecarbamate, a new, potent anthelmintic.

1. Human hepatic "acid" beta-galactosidase preparations, which had been purified approximately 250-fold, were examined for activities toward 4-methylumbelliferyl beta-galactosylceramide, lactosylceramide, galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosyl-glucosylceramide(GM1-ganglioside) and galactosyl-N-acetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM1-ganglioside). 2. The enzyme was active toward the synthetic substrate, GM1-ganglioside and asialo GM1-ganglioside but was inactive toward galactosylceramide. Under our assay conditions, optimized for lactosylceramidase II, the preparations were as active toward lactosylceramide as toward GM1-ganglioside or its asialo derivative. The apparent Km values for the three natural substrates were similar. When determined by the assay system of Wehger, D.A., Sattler, M., Clark, C. and McKelvey, H. (1974) Clin. Chim Acta 56, 199-206, lactosylceramide-cleaving activity was 0.2% of that determined by our assay system. This confirmed our previous suggestion that the Wenger assay system determines exclusively the activity of lactosylceramidase I, which is probably identical with galactosylceramide beta-galactosidase. 3. Crude sodium taurocholate was far more effective than pure taurocholate in stimulating hydrolysis of the three glycosphingolipids by the beta-galactosidase. However, crude taurocholate could largely be replaced by smaller amounts of sodium taurodeoxycholate, suggesting that the unique activating capacity of the crude taurocholate might be due to taurodeoxycholate present as the major impurity. 4. Cl- was generally stimulatory for hydrolysis of the natural glycosphingolipids by our enzyme preparation. Effects of additional oleic acid and Triton X-100 were generally minor in either direction. 5. When the enzyme preparation was diluted with water, activity toward the synthetic substrate declined rapidly while those toward the natural substrates were essentially stable. Activity toward the synthetic substrate remained much more stable when the enzyme was diluted with 0.1 M sodium citrate/phosphate buffer, pH 5.0. 6. These observations provide insight into the complex relationship among the human hepatic beta-galactosidases.


Specific chromosome aberrations in ataxia telangiectasia.

Cytogenetic observations on seven cases of ataxia telangiectasia are presented. The aberration frequency was found to be increased in all of them with a specificity for the involvement of the D-group chromosomes in rearrangements. Clones of cytogenetically abnormal cells were observed in the lymphocytes of three cases and in the cultured skin fibroblasts of two cases, again with a specificity for D-group involvement. G-banding shows that chromosome 14 is frequently involved in rearrangements in clone cells and that the band 14q12 may be a highly specific exchange point. The significance of lymphocyte clones with a proliferative advantage in vivo is discussed. Cytogenetic studies of the parents and sibs of these cases are also reported.


Identification of C trisomies in human abortuses.

Fifteen cell lines initiated from embryonic tissues of abortuses with C trisomy were frozen and stored. They were thawed and karyotyped again with banding techniques. Trisomies 7, 8, 9, 10, and 12 were identified. Some characteristics of these abortuses are discussed in connection with the chromosome identifications.


Homozygous haemoglobin D Punjab.

A homozygote for the gene controlling Hb D Punjab is described. The diagnosis is supported by the peptide analysis of the haemoglobin and the examination of both parents. There was no anaemia or reticulocytosis and there was balanced synthesis of both the alphaA- and betaD-globin chains in reticulocytes. However, the oxygen affinity of the haemolysate had a small but significantly higher oxygen affinity than normal. The only other abnormalities were a somewhat decreased osmotic fragility and a slight anisocytosis of the red cells.


Haemoglobin Lepore in Cyprus.

Structural analysis documented the presence of haemoglobin LeporeWashington (=LeporeBoston) in a Greek Cypriot family and provided further evidence that, of the various types of Lepore mutants, only one is common in the Mediterranean area. Two individuals in this family were heterozygous for both Hb Lepore and beta thalassaemia, but they exhibited striking differences in the clinical severity and course of the disease. The data illustrate that additional environmental or genetic factors play roles in determining or modifying the pathophysiological consequences of highly specific molecular defects and, thus, their ultimate clinical phenotypes.


Ocular colobomata, cardiac defect, and other anomalies: a study of seven cases including two sibs.

An association of ocular colobomata and congenital heart disease was observed in seven patients. Two of these were maternal half sisters whose mother also had ocular colobomata. All the patients had normal karyotypes. There was a high incidence of other associated abnormalities involving the central nervous, skeletal, and urogenital systems. Discovery of an ocular coloboma should alert the clinician to search for other abnormalities.


Haemoglobin Hasharon in a north Italian community.

A survey of haemoglobin variants undertakin in an Italian community (Polesine) has revealed the presence of haemoglobin Hasharon (alpha2 47 Asp yields His beta2) in 108 subjects from 40 families. The variant accounted for 30 to 40% of the total haemoglobin. In subjects doubly heterozygous for Hb Hasharon and beta thalassaemia, the proportion was 17 to 19%. Though there was some evidence that the variant was unstable in vitro, there was no obvious haemoglobinopathy in vivo.


A new case of haemoglobin Bucuresti in a Cuban family: further functional studies.

A new case of haemoglobin Bucuresti beta 42 (CD1) Phe yields Leu is described in a Cuban family. The functional studies confirm the results already described--a low oxygen affinity and a decreased haem-haem interaction. In addition to this, the reactivity for 2, 3 diphosphoglycerate (2, 3 DPG) was shown to be normal. The instability is mostly due to a fast rate of haemichromes formation.


Klinefelter's syndrome associated with a D/D translocation.

A case of Klinefelter's syndrome and a simultaneous familial D/D translocation is described. The clinical, endocrine, and psychiatric features were typical of those found in Klinefelter's syndrome. Other family members showed no obvious abnormality despite presence of the D/D translocation.


Partial 9 trisomy by 3:1 segregation of balanced maternal translocation (7q+; 9q-).

A male infant is presented with an extra derivate chromosome No. 9 resulting from a 3:1 meiotic segregation of a maternal balanced translocation involving the long arms of chromosomes No. 7 and 9. The patient is trisomic for the short arm and secondary constriction of the long arm of No. 9 and for the telomeric end of the long arm of No. 7. In addition to the features of the 9p trisomy syndrome he presents marked congenital myopia and extreme hypoplasia of the penis.


Pseudohermaphroditism with clinical features of trisomy 19 in an infant trisomic for parts of chromosomes 16 and 18: 47,XY,der(18),t(16;18)(p12;q11)mat.

The case is presented of an infant who was diagnosed clinically as trisomy 18 with pseudohermaphroditism. Cytogenetic studies revealed an extra chromosome which represented a translocation chromosome derived from a balanced, reciprocal translocation between chromosomes 16 and 18: [der(18),t(16;18)(p12;q11)mat]. The infant's mother and a number of her relatives were found to be translocation carriers: ]46,XX,t(16;18)(p12;q11)].


A syndrome of hypohidrotic ectodermal dysplasia with normal teeth, peculiar facies, pigmentary disturbances, psychomotor and growth retardation, bilateral nuclear cataract, and other signs.

This paper describes a 7-year-old girl with trichodysplasia, normal teeth, onychogryposis, hypohidrosis, psychomotor and growth retardation, dry and warm skin with follicular hyperkeratosis, pigmentary disturbances (hyper- and hypochromic spots), bilateral nuclear cataract, dermatoglyphic anomalies, and other signs. This condition is considered a new form of ectodermal dysplasia.


A case of partial (9p) trisomy in a family with a balanced translocation 46,XX,t(1p+9q-).

A case of partial trisomy 9 is described, conforming that this will produce a recognizable syndrome of a characteristic facies with deep-set eyes and an unusual shape of the nose. Failure of secondary sexual characteristics to develop appears to be a feature in adults. In this case the mother had a balanced translocation between chromosomes 1 and 9 and must have, in addition, had a non-disjunction of her normal and her deleted No. 9 in order to produce the unbalanced state in her daughter.


Ultrastructure of L-phase variants isolated from a culture of Mycobacterium phlei.

Relatively stable L-phase colonies were isolated from old cultures of a selected clone of Mycobacterium phlei. The colonies grew at 52 degrees C and were composed of rod-shaped, oval or spherical cells. Large amoeba-like cells were occasionally present. These were usually limited by a double-layered membrane and devoid of normal cell-wall components such as bacteriophage receptors. The large amoeba-like bodies sometimes showed both outer and inner double-layered membranes, especially in pseudopodium-like cellular extensions. An unusual feature of rod-shaped cells was retention of the original shape despite the loss of their cell walls. Two types of walled cells occurred during successive transfers of L colonies. One was the true revertant which had characteristics in common with the wild-type M. phlei, such as growth at 52 degrees C and ultrastructural organisation. The other, designated as the "atypical-cell-wall variant", was characterised by growth at 52 degrees C, thick cell walls, and disordered septation. Wild-type M. phlei, L variants, revertants and atypical-cell-wall variants released mycobacteriophage particles. These bacteriophages were almost identical in respect to morphology, host range, and neutralisation by antiserum. The results obtained suggest strongly that all types of cells examined were derived from M. phlei.


Observations on the growth and movement of Acinetobacter on semi-solid media.

The growth of 29 strains of Acinetobacter spp. on semi-solid media was studied; 19 showed surface swarming and 14 produced channels ("ditches") in the agar that do not seem to have been described previously. An attempt was made to define the cultural and physical conditions for the demonstration of these phenomena. Possible taxonomic implications are discussed.


The nuclear dehydrogenation of steroids by intestinal bacteria.

We have postulated that bacteria able to dehydrogenate the bile-acid nucleus are important in the aetiology of cancer of the colon. In this paper we report on screening for the ability to carry out two such reactions. The relevant enzymes are produced by a high proportion of strains of Clostridium paraputrificum, C. tertium and C. indolis, and by small numbers of strains in other clostridial species, but not by organisms of the other genera tested. Strains able to dehydrogenate the bile-acid nucleus represent a high proportion of the lecithinase-negative clostridia isolated from faeces of people living in Britain but a low proportion of those from people living in Uganda or Hong Kong.


Observations on group-F streptococci from human sources.

In a 4-year study, 22 strains of group-F streptococci were isolated from children and puerperal women. All were isolated in mixed culture but were associated with sepsis or other pathological conditions. It appears that this organism may be an opportunistic pathogen and that its habitats include the gastrointestinal tract and the vagina as well as the throat.


The role of proteins in a dipole model for steady-state ionic transport through biological membranes.

The steady-state current-voltage characteristics of biological membranes are analyzed for means of an application of the electrodiffusion theory to the passage of ions through "dielectric pores", with orientable dipoles at the pore-water interfaces. A detailed evaluation of the electrostatic potential barrier shows, indeed, that the ions have practically no chance to penetrate into the phospholipid bilayer, but that they can cross the membrane through local protein inclusions, of high dielectric constant. A "gating mechanism" can be provided, moreover, by a change of the potential barrier, resulting from a dipole reorientation at the pore-water interface. Dipole-dipole interactions are opposed to the orienting effect of an applied field, but they can be neglected when the separation between the dipoles exceeds a certain critical value. The high polarizability of the pore material leads to an amplification of the effect of an applied field on the orientable dipoles. It is therefore possible to achieve a satisfactory agreement with the experimental results of Gilbert and Ehrenstein (Biophys. J., 9: 447, 1969) for the squid axon, and, in particular, to account for the width of the negative resistance regions with a relatively small value for the length of the orientable dipoles.


Phylogenies from amino acid sequences aligned with gaps: the problem of gap weighting.

The common but generally overlooked problem of how best to construct phylogenies from orthologous amino acid sequences, when their alignment requires the placement therein of gaps denoting insertions/deletions in the evolutionary history of their genes since their common ancestor, has been studied. Three diverse methods were examined: 1. each missing residue in a gap is weighted as equivalent to the average number of minimum nucleotide replacements in known conjugate amino acid pairs of those same two sequences, which weight necessarily differs for each pair of sequences; 2. each missing residue in a gap is weighted as equivalent to a fixed number of nucleotide replacements; and 3. each gap, regardless of length, is weighted as equivalent to a fixed number of nucleotide replacements. For the flavodoxins, each method yielded a different best tree and suggests that the choice of method may be crucial. For the plant ferredoxins, all methods give results inconsistent with botanical classification and suggests the sequences may not all be orthologous. For the bacterial ferredoxins, the method was less germane than the actual weight used, five different best trees being obtained depending upon the weight. The best tree for all ferredoxins (prokaryotic plus eukaryotic) combined proved to be greatly dependent upon the gap locations with several reasonable aligments yielding different best trees. They also suggest that functional equivalence may well prove to be a poor guide to which residues have a common ancestral codon. The rubredoxin sequences show that a partial internal gene duplication occurred in the Pseudomonas line, probably very soon after its divergence from the other genera. Together, the results clearly indicate that the phylogenetic answer one gets may greatly depend upon how one treats the gaps but they fail to indicate what treatment may be best.


The nucleotide sequence of the 5S ribosomal RNA from a photobacterium.

Comparative sequencing studies provide powerful insights into molecular function and evolution. The sequence for 5S ribosomal RNA from Photobacter strain 8265 is eighteen base replacements removed from that of Escherichia coli. Of these, the vast majority involve a G or C becoming an A or U. These variations also define unequivocally a hexanucleotide base paired region, which appears to be a universal feature of the 5S RNA molecule. The base composition of this helix seems to be under rather stringent, and so unusual, energetic constraints. The possible implications of this are discussed - in particular the prospect of a 5S RNA molecule that undergoes conformational transitions as a part of the overall state changes that constitute the function of the ribosome.


Partial gene duplication and posterior pituitary peptide.

We have compiled the dipeptide frequencies in 100 known protein sequences. We suggest that dipeptides which occur with low frequencies can be used to locate proteins where partial gene duplication may have taken place. The 48 residue sequence of posterior pituitary peptide contains two Cys Trp pairs. The adjacent portions of the sequence are compatible with a partial gene duplication in the evolutionary history of posterior pituitary peptide.


Prebiotic peptide-formation in the solid state. I. Reactions of benzoate ion and glycine with adenosine 5'-phosphorimidazolide.

The reactions of benzoate ion and of glycine with adenosine 5-phosphorimidazolide have been investigated. Benzoate reacts first to give the anhydride, benzoyl-adenylate, which, in the presence of excess imidazole, reacts further to give the 2'- and 3'-esters of adenosine 5'-phosphate. Glycine also first attacks the imidazolide to give an anhydride, but this compound may react further either to give 2- and 3'-esters or to form peptides, depending on the reaction conditions.


DNA: DNA hybridization studies in black flies.

The phylogenetic relationships of six species of black flies were investigated using the hybridization of iodinated unique DNA sequences. The thermal stability of these labelled hybrids allowed the construction of a phylogenetic tree based on base mismatch between chains of the heterologous duplex.


Factors influencing outcome after blunt duodenal injury.

Thirty-six patients with blunt duodenal injury have been treated at Detroit General Hospital since 1960. The majority of the patients were driving an automobile under the influence of alcohol and none were wearing seat restraints. Diagnosis was often delayed due to a failure to recognize the significant, but subtle, physical and roentgenographic findings of retro-peritoneal injury. Morbidity and mortality were related to a delay in operative intervention, the severity of duodenal injury, the presence and degree of associated pancreatic injury, and the choice of operative therapy. Patients with intramural hematoma or complete duodenal perforation without pancreatic injury did well with simple closure or evacuation of the hematoma. Patients with duodenal perforation and minor pancreatic injury did best after primary closure and pancreatic drainage if operation was performed within 24 hours; delay beyond 24 hours resulted in a high incidence of duodenal fistula after simple closure, and therefore is an indication for a bypass procedure, such as a distal gastrectomy, vagotomy, tube duodenostomy, and gastrojejunostomy. Patients with combined duodenal and major pancreatic disruption did best after a bypass procedure when the main pancreatic ductal system was intact, whereas pancreaticoduodenectomy was the best procedure when the main pancreatic duct was disrupted.


Traumatic injuries of the duodenum: a comparison of 1 degrees closure and the jejunal patch.

Twenty-two traumatic injuries of the duodenum were reviewed. In this series either primary closure, or primary closure plus the jejunal serosal patch prove satisfactory methods of repair. The addition of the jejunal serosal patch may be more secure but its superiority could not be documented in this small series. The mortality was related to the associated organ injuries. When blunt or penetrating injuries to the duodenum alone occur, there should be minimal mortality.


Diagnostic peritoneal lavage in blunt abdominal trauma.

Diagnostic peritoneal lavage is accurate and safe. It leads to fewer unnecessary laparotomies than if clinical examination alone is used and nearly eliminates deaths from undiagnosed abdominal injuries. Persons with clinical abdominal findings, shock, altered sensorium, and severe chest injuries after blunt trauma should undergo the procedure.


Ambulatory treatment of femoral shaft fractures with cast-brace.

Our early results support use of the cast-brace, early ambulation treatment of both open and closed fractures of the femoral shaft in all adult age groups. We believe initial traction should be used to reduce the fracture and maintain reduction until the fracture is clinically "sticky" to avoid subsequent malalignment in the cast-brace. The method facilitates early rehabilitation of the fractured extremity and the patient with minimal residual disability such as non-union, malunion, chronic infection and joint stiffness, so often associated with other forms of long bone fracture treatment.


Improved healing of experimental long bone fractures in rabbits by delayed internal fixation.

Experiments in rabbits were conducted to test the clinical propositions that a) the risk of nonunion in certain long bone fractures can be sharply reduced by open reduction and internal fixation, and b) that there is an optimum critical period following trauma in which this procedure should be carried out to facilitate healing. Bilateral standard open fractures of rabbit radii were internally fixed by intramedullary K-wires immediately or at 5, 10, and 17 days after trauma. These bones were subjected to stress and histometric analyses at 4-56 days after the initial fractures. The observations suggested that the pace of fracture healing could be optimized by time-delay surgery. The most exuberant and strongest calluses developed when the bones were fixed 10 days after fracture, and the rate of healing was improved. Delay times of 5 or 17 days did not provide better healing than that achieved by an immediate operation. Callus quality, in terms of the proportion of fiber bone, lamellar bone, and cartilage, was similar in all groups. The tensile strengths of the bones during callus formation were highly correlated with the ratio of callus/cortical bone areas (p less than 0.01).


Intrarenal redistribution of blood flow in the early postburn period.

We interpret the findings of the present study and other studies reported here to indicate that alterations of renal outer to inner cortical blood flow distribution develop in the early postburn period. These alterations are similar to those observed by other investigators in animals subjected to various other traumatic events. Such flow redistributions were observed in both untreated animals and those receiving intravenous fluid resuscitation. Sharp reductions in urinary chloride and sodium concentrations observed in conjunction with these blood flow shifts may be a reflection of the relatively greater perfusion of juxtamedullary nephrons, which are alleged to have greater salt-retaining characteristics than their outer cortical counterparts.


Acute liver disease after cutaneous thermal injury.

To better define the acute liver disease complicating thermal injury, 81 burn patients were evaluated for hepatic damage. Clinical and laboratory evidence of hepatocellular injury was present as early as 24 hours after burn in 47 patients (58%). Patients with liver disease had a larger mean burn size (p less than 0.01) and greater mortality than patients with normal liver studies. The magnitude of initial enzyme derangements did not distinguish the survivors, but jaundice was associated with a poor prognosis. Seventeen of the 19 jaundiced patients (90%) died. The early occurrence of hepatocellular injury suggested that acute hemodynamic alterations were important etiologically. Intrahepatic cholestasis and jaundice developed later in septic or hypoxic patients and was accentuated by hemolysis and blood transfusions. In these patients, liver histology showed a nonspecific hepatitis. An increased risk of septic complications could not be attributed to the presence of liver disease. Late emergence of conjugated hyperbilirubinemia suggested an underlying septic process.


Current concepts in the management of penetrating neck trauma.

Six hundred thirty-two cases of penetrating wounds of the neck were analyzed in this study in order to re-evaluate our current concepts in the management of these injuries. There were 35 deaths in this series, an overall mortality rate of 5.5%. However, in the last 10 years there were only 13 deaths among 407 patients, a 3.2% mortality rate. Early exploration was performed in 507 patients, and 125 patients were observed. Explorations revealed a total of 625 separate injuries. In 142 explorations, no injury was found. There was no mortality or significant morbidity in these patients with negative explorations. Patients who presented with obvious vascular or visceral injury were immediately explored. Those wounds without obvious injury were either explored or observed, depending on the index of clinical suspicion based on awareness of the innocuous presentation and difficulty in diagnosing esophageal injuries. The mortality rate is a function of multiple factors. Its decrease over the past 25 years is related to many improvements in our health care system. Our own decrease in mortality rate can be attributed in part to decreased transportation time resulting in less blood loss. A greater awareness of esophageal injuries was another factor. No conclusions are possible as to the feasibility of conservative management based upon the mortality rates alone; however, on examination of our experiences with penetrating wounds of the neck, it appears that a significant number of patients when carefully selected by trained personnel can be safely managed with observation.


Thumb length preservation following soft tissue injuries.

Six cases of major soft-tissue injuries to the mid or base of thumb are presented. In each case, pedicle reconstruction of the soft tissues was necessary in order to preserve thumb length. A variety of techniques was used, including distant tissues and local tissues. We have illustrated the superiority of local pedicles and cross-finger pedicles in thumb reconstruction and have emphasized the following points: 1) Preservation of thumb length is an important goal. 2) Conservation of the soft tissues in the initial management plays a key role in thumb reconstruction. 3) Local pedicles and cross-finger flaps have given better results than distant flaps, as evidenced by: a. better sensory capacity in the pedicle skin; b. more stable skin on the reconstructed thumb; c. less bulkiness of the pedicle skin; d. reconstruction is less time consuming.


Primary peripheral nerve repair in the hand and upper extremity.

A small consecutive series of primary nerve repairs in civilian injuries demonstrates that normal two-point discrimination and stereognosis can be anticipated not only in digital-nerve injuries but in mixed sensory and motor nerve injuries. Motor return follows and approaches normal in most patients. During the study period, 15 delayed repairs of mixed nerve lacerations were done. Two-point discrimination and stereognosis did not return to normal in any of the patients with mixed-nerve injuries or in one quarter of those with sensory-nerve injuries. Motor return never graded better than 3 on a scale of 0-4. Therefore, this author feels primary repair is superior to secondary repair and that almost all civilian injuries can be made surgically clean by debridement.


Temporary external shunt bypass in the traumatically amputated upper extremity.

The technique of temporary external shunt bypass offers early perfusion of a traumatically amputated extremity, thus decreasing the total anoxic time, permitting bony fixation after perfusion is established, and allowing arterial revascularization with good venous outflow and minimal blood loss. This technique may increase the survival of these severely damaged limbs.


Delayed post-traumatic subdural empyema.

A case of subdural empyema is reported, treated through a frontal bone flap, with exenteration of the infected frontal sinus at operation, and subdural instillation of antibiotics for 48 hours postoperatively. Diagnostic findings are reviewed, and the likelihood of anaerobic infection this case and similar cases discussed.


High-pressure silicone injection injury of the hand.

A case of room-temperature vulcanizing (RTV) silicone injection of the hand is presented, and principles of management of high-pressure hand injuries are outlined. Early debridement and decompression are urgent in the acute stage of injury. Intermediate stages require adequate coverage and mobilization, and late stages involve reconstructive procedures. As in all high-pressure hand injuries, safety measures and prevention at the industrial level are very important.


Avascular necrosis of the head of the talus without death of the body: report of an unusual case.

A case of fracture of the neck of the talus with dislocation of the subtalar joint is reported in which the head of the talus underwent avascular necrosis while the body remained alive.


Replantation of the severed ear.

A successful replantation of a completely amputated ear segment using the modified subcutaneous pocket principle has been presented. This method overcomes most of the disadvantages of other reconstructive techniques.