The treatment of refractory anaemia of chronic renal failure with cobalt chloride.

Twelve anephric patients on maintenance haemodialysis received treatment with oral enteric coated cobalt chloride 25 to 50 mg daily. The change in haemoglobin concentration, and packed cell volume, are recorded and discussed with special reference to possible toxicity and mechanism of action of cobalt. Six of eight patients who completed the first course with cobalt chloride 50 mg daily for 12 weeks showed a significant rise in haemoglobin concentration of 26 to 70 per cent and a fall to near pre-therapeutic levels when cobalt was withdrawn. Evidence of a response was present within two months of starting treatment. Four patients showed a diminution in their blood transfusion requirements and three patients experienced a definite sense of increased well-being during treatment. One patient suffered from side effects of the drug and failed to complete the study because of gastrointestinal disturbance. The improvment in haemoglobin concentration was reproducible in four patients who were given second, and in one case third courses courses with varying doses of cobalt over differing periods of time. Serum cobalt levels tended to stabilize after two months continuous treatment to the therapeutic range of 40-100 mumg per 100 ml. A rapid fall in serum cobalt was seen on cessation of treatment. It is suggested that therapy with enteric coated cobalt chloride at a dose of between 25 and 50 mg per day has a definite place in the treatment of the refractory anaemia of chronic renal failure.


Disposition kinetics of dihydroquinidine following quinidine administration.

The disposition kinetics of dihydroquinidine, a known impurity in drug grade quinidine, was studied in 7 patients who were hospitalized for control of cardiac arrhythmias. Quinidine gluconate injection containing 5.4 to 6.2 percent dihydroquinidine was used. Following an overnite fast, dihydroquinidine doses of 0.16 to 0.31 mg/kg base were infused intravenously over 22 min. Plasma samples were collected at various times for 12 hr and analyzed for dihydroquinidine by a thin layer chromatography-fluorometric assay procedure. Postinfusion plasma dihydroquinidine concentration decline was described by a biexponential equation which suggested that the impurity distributes within the body in two kinetically distinguishable pools. The volume of the central pool (Vc) and steady-state volume of distribution (Vdss) were 0.67 +/- 0.15 L/kg and 2.76 +/- 0.63 L/kg, respectively. The halflife of the fast (t1/2alpha) and slow (t1/2beta) disposition processes were 4.71 +/- 0.26 min and 5.71 +/- 1.00 hr. Total plasma clearance was 4.17 +/- 0.68 ml/min/kg. Renal excretion of intact dihydroquinidine accounted for 16 percent of the administered dose. The corresponding value for renal dihydroquinidine clearance (Clr) was 0.61 +/- 0.08 ml/min/kg. The results of this study indicated that there were no significant differences in the distribution and elimination characteristics of dihydroquinidine and quinidine.


Inhibition of 3H-1-norepinephrine uptake by ouabain is species dependent.

Tissue slice to medium ratios of 3H-1-norepinephrine (3H-1-NE) were used to study the effect of ouabain on uptake of norepinephrine. The effects of ouabain were studied in slices of heart and spleen from three different species: rat, guinea pig, and dog. The drug produced a species as well as a concentration dependent inhibition of norepinephrine uptake in both types of tissue. In order of decreasing sensitivity, the following relationship between species was observed: dogs greater than guinea pigs greater than rats. Since 3H-1-norepinephrine uptake under the present experimental conditions represents uptake into sympathetic nerve terminals, it was concluded that Na+-K+-ATPases of sympathetic nerve terminals have species dependent differences in ouabain sensitivity similar to those of myocardium.


[Perirenal lipoma. Histochemical study (author's transl)].

The occurrence of unilateral perirenal lipoma in an adult female patient is reported. Histochemical reactions, which were performed to search the tumor's nature, showed the presence of unsaturated neutral fat.


Influence of morphine on protein synthesis in discrete subcellular fractions of the rat brain.

Extensive time course (15 min to 24 hr) measurements were made of the effects of acute and chronic morphine treatment on the incorporation of 3H-lysine into rat brain proteins. Acute and chronic morphine treatment inhibited cortical protein synthesis in the microsomal (Mc), mitochondrial (Mw) and soluble fractions (Sol.). In the subcortex, acute morphine stimulated labelled protein accumulation in the Mc and Mw fractions, Chronic morphine treatment decreased 3H-lys-protein accumulation in these fractions.


Hydrolysis of carbon-labeled cocaine in human serum.

Hydrolysis of 14C-cocaine in human serum, separation of the metabolites on TLC, and subsequent identification on GLC is described. AT 1 H, 20 percent of the cocaine was metabolized to benzoylecgonine, ecgonine and ecgonine methylester. At this time interval the highest percent of product was in the form of the ecogonine methyl ester, a metabolite not previously reported in humans. After 4 h, 67 percent of the cocaine was hydrolyzed; of this, 45 percent was benzoylecgonine and ecgonine in a ratio of 1.6 to 1. The half-life for cocaine hydrolyzed in human serum was approximately 2.5 h.


Synthesis and characterization of a catechol metabolite of glutethimide (Doriden) in human urine.

A metabolite of glutethimide, 2-ethyl-2-(3,4-dihydroxyphenyl)-glutarimide, previously identified in enzymatically hydrolyzed human urine of overdosed victims was prepared synthetically and its chemical and spectral data compared to the proposed material. Results of these comparisons confirm the presence of a catechol metabolite of glutethimide in the urine of patients severely intoxicated by the parent drug.


Inhibition of human erythrocyte acetylcholinesterase by succinyldicholine.

When human erythrocyte acetylcholinesterase (AChE) is inhibited by succinyldicholine (SuCh) at low ionic strength, mu = 0.03, two apparent affinity constants for the inhibitor can be distinguished, KI(1) = 5.4 X 10-5 M and KI(2) = 1.3 X 10-5 M. Increasing the ionic strength to mu = 0.58 increases KI(1) to 1.1 X 10-4 M, but abolishes the contribution of KI(2) completely. It is suggested that a similar process may underlie the apparently continuous variation in affinity constant with ionic strength which has been reported for many bifunctional cationic inhibitors. Since KI(2) is in a concentration range commonly attained therapeutically, some of the clinical manifestations of succinyldicholine administration, e.g., muscarinic effects, may be explained by its anticholinesterase action.


Instability of mixed function monooxygenases in frozen rat liver.

The effect of freezing in liquid nitrogen and storage at -74 degrees C on various parameters of rat livers from phenobarbital-induced and untreated animals was investigated. Marked instability of microsomal aminopyrine N-demethylase activity and cytochrome P-450 content were detected upon freezing and immediate thawing, leading to the conclusion that this may not be an acceptable means of storage of rat liver for studies of the mixed function oxidase enzymes.


[Internship in a community hospital. Experience gained in the "Faculdade de Ciências Médicas e Biológicas de Botucatu" (author's transl)].

Currently the verification of the equivalence between an University Hospital (U.H.) and a Community Hospital (C.H.), in means of internship accomplishment is an important subject. The F.C.M.B.B. has accumulated experience in this matter, since among the 514 doctors graduated at this school, in the period of 1968 to 1973: 309 accomplished their internship at Botucatu (U.H.); and the remainers 205 at C.H.s. The author's purpose was to try to evaluate the existence, or not, of this equivalence. Thus two different questionnaries were elaborated, one that was answered by two kinds of intern's instructors (total 58): the teaching staff of U.H. (33), and the physicians belonging to the staff of one of the C.H.s. The other was submitted to two groups of ex-interns (total: 73): ex-interns from U.H. (53) and from C.H.s. (20). Both, ex-interns and teachers, were selected by chance. The answers were analysed by stablishing a comparison between the two groups: U.H. and C.H. The results were analysed by chi2 (chi-square) using the Yates correction for 2 X 2 tables. They seem to suggest that there is an equivalence between U.H.s. and C.H.s. in means of internship accomplishment, since certain characteristics are observed by the C.H.s.


Chronic inhalation of marijuana and tobacco in dogs: pulmonary pathology.

The pulmonary effects of chronic marijuana (M) and tobacco (T) smoke inhalation were studied in adult female dogs. The smoke was inhaled through a tracheostomy tube: four cigarettes containing either tobacco (3.2 g/dog) or marijuana (3.0 g/dog) were used per day over 900 days. At autopsy, the pulmonary volume and alveolar surface of the T group had decreased, compared to controls (C) and the M group. The tracheostomy (Tr) produced itself result in chiolitis; in order of severity the M group greater than T greater than Tr greater than C. The incidence of squamous metaplasia also followed this order but the T group showed more abnormalities affecting the mucosal membrane. Our findings reported that chronic inhalation of marijuana and tobacco produced the bronchiolitis with the macrophage infiltration in the wall of the terminal air-passages. This may thereafter induce the pulmonary emphysema.


Comparisons of carcinogenicities of nickel compounds in rats.

This study demonstrates marked differences in the incidences of sarcomas in Fischer rats within 2 years after a single im injection of 4 insoluble nickel-containing powders: amorphous nickel monosulfide (NiS), nickel subsulfide (alphaNi3S2), partially converted nickel-iron sulfide matte, and metallic nickel. The powders (less than 2 um median particle diameters) were administered in penicillin suspension, and each powder was tested at 2 dosages. Whereas alphaNi3S2 was highly carcinogenic, amorphous NiS did not induce any tumors. The carcinogenic potency of partially converted nickel-iron sulfide matte was less than alphaNi3S2 but greater than Ni powder. No sarcomas occurred at the injection site in two groups of control rats that received im injections of penicillin or Fe powder. The observed differences in carcinogenic potencies of alphaNi3S2 and amorphous NiS may provide an experimental approach to elucidate the molecular mechanisms of nickel carcinogenesis.


Purine excretion by cultured skin fibroblasts from patients with abnormal purine metabolism.

Cultured fibroblasts from patients with partial or complete deficiencies of enzymes involved in purine metabolism provide a model for investigating the biosynthesis, interconversion, and excretion of purine metabolites at the cellular level. Skin fibroblast cultures were derived from five patients with hypoxanthineguanine phosphoribosyltransferase deficiency, from five subjects with idiopathic overproduction gout, from one patient with adenosine deaminase deficiency, and from four control subjects. Purine excretion was measured by recovering labeled purines from the incubation medium of cells grown in the presence of 14C-formate. In general the patterns of purine excretion by these cultured cells resembled the urinary excretion patterns of the patients from whom they were derived.


Apparent deficiency of vitamin B6 in typical individuals who commonly serve as normal controls.

Individuals who typically serve as normal controls were found by the differential assay of the glutamic oxaloacetic transaminase in their erythrocytes to have a deficiency (P less than 0.001) of enzyme activity as well as a deficiency (P less than 0.001) of pyridoxal phosphate. Contrary to the understanding that the diet provides an adequate intake of vitamin B6, the dietary intake of vitamin B6 of these controls was inadequate.


Thin-layer and gas chromatographic determination of ketamine and its biotransformed products in biological fluids.

Ketamine, (2-(o-chlorophenyl)-2-methylamine cyclohexanone) and its in vivo metabolite I (2-(o-chlorophenyl)-2-aminocyclohexanone) and metabolite II (2-(o-chlorophenyl)-2-amino-5-cyclohexene-1-one) were determined by thin-layer (TLC) and gas chromatography (GC). In vivo studies include intraperitoneal injection of ketamine in rats. Urine and blood samples were collected at regular intervals. The unreacted ketamine and its biotransformed products were extracted from urine and blood and subjected to TLC and GC analysis. 1% Carbowax-20M on Gas Chrom G-AW-DMCS and precoated LQ6D TLC plates were used in this study. In conclusion a rapid, simple, accurate, and sensitive thin-layer and gas chromatographic method for the identification of ketamine and its metabolites from biological fluids have been developed.


An automated method for the determination of sulfate.

An automated method of sulfate analysis is described, which can detect sulfate concentrations as low as 2.5 mug per ml water. The assay is based on the reaction of sodium rhodizonate and barium forming a colored complex. Sulfate quantitavely interferes with this reaction. The assay is reproducible in the range of 2.5 to 30 mug sulfate per ml water. This method conveniently and accurately measures water soluble sulfate filtered from the air, and is especially useful in assaying samples containing microgram quantities of sulfate from experimental inhalation apparatus.


Potentiophotometry.

The present derivation relates, in terms of analytical chemical photometry, the theory of operation of an extremely simple instrument which embodies both the electrical analog solution to Beer's Law of Spectrophotometry and the multiplication of this solution by a constant, such that the voltage reading of the instrument is identical to the concentration of the light absorbing substance being measured. Because the raw output of the instrument is both linear and proportionable, calibration of the instrument is accomplished by appropriately setting and positioning the potential difference between two known standard solutions. The determination of the concentration of an unknown solution is then the direct reading of the voltage it generates in the system. This approach to measurement is called Potentiophotometry, because it is based on potentials generated from light.


[Giant cell granulomatous angiitis of the central nervous system].

The case is described of a coloured woman of 58, previously affected by filaria, who presented with meningo-encephalitis which proved fatal within a month. Pathological anatomy showed granylomatous angiitis with giant cells scattered throughout the brain and the meninges but confined exclusively to the nervous system. Biological and anatomopathological tests were unable to connect this condition with any precise aetiology. The aetiology of granulomatous angiitis is discussed in this connection and the clinical and anatomopathological charateristics peculiar to giant cell granulomatous angiitis of the nervous system are recalled.


[Dopamine beta hydroxylase. Value and limits of its study in neurology].

Plasma dopamine-beta-hydroxylase was studied in 96 subjects, 33 of them controls and 63 of them patients (Parkinson's disease, chronic chorea, torsion dystonia, postural tremor and epilepsy). Only the epileptics showed a significant decrease in the average level of dopamine-beta-hydroxylase activity in comparison with the controls. During the cold test, DBH did not vary except in one case. On the other hand, during epileptic attacks, DBH activity underwent considerable fluctuations. Therefore, except in special pathological conditions, such as epileptic attacks, measurement of plasma or serum DBH activity is of limited value for neurological pathology and is not a good indication of the activity of the sympathetic nervous system.


Surgery on the lateral nasal wall with the operation microscope.

Experiences with operations on the lateral nasal wall and the ethmoid with the operating microscope are reported. 18 suitable cases were operated on according to this technique. For the optimal distance optics with a focal distance of 250 mm are most suitable. Prerequisites for the operations are a self-supporting speculum and special instruments developed for this purpose.


[Experimental study of the synthesis of lysosomal enzymes by the synovial membrane: acid phosphatases].

In a system consisting of synovial samples taken surgically and maintained in culture, the authors studied the regulation of enzyme synthesis by taking acid phosphatase as the test enzyme. By means of double labelling and the use of protein synthesis inhibitors, they were able to demonstrate that this synthesis was stimulated by the addition of rheumatoid factor to the culture medium and that it depended on the transcription activity of the genome and on the translation of the information molecules.


[Cellular density of the femur head cartilage in  relation to age].

The authors studied the cell density in samples of cartilage taken from the superior and inferior poles of the femoral heads of 65 subjects between 16 and 100 years of age. This study showed that the average cell density of the cartilage decreased significantly with age and that the decrease was proportionally identical in the two poles of the femoral head. In absolute values, the decrease in superficial cell densty is much greater in the inferior than in the superior pole. The relation between the decrease in cell density with age, cartilaginous lesions of senescence, and arthrosis are discussed.


Cadmium and zinc in human liver and kidney.

Liver and kidney samples obtained from 76 autopsies were analyzed for cadmium and zinc content. The patients had died of various internal diseases. None of them had any known occupational exposure to cadmium. A record was made of age, sex, place of residence, diagnosis, and smoking habits of each patient. The results showed no significant correlation between cadmium accumulation and hypertension or cardiovascular disease. There was, however, a significantly higher kidney cadmium level in smokers than in nonsmokers.


Separation of labelled iodide, iodoprotein, iodotyrosines, and iodothronines in serum from patients treated with iodine-131, using an improved chromatographic method.

A method is described for complete separation of iodoprotein, 3-iodotyrosine (MIT), 3,5-diiodotyrosine (DIT), 3,5,3-triiodo-L-thyronine (T3), and L-throxine (T4) on a single column run on Sephadex G-25 superfine in alkaline solution. Sera from patients treated with 131I- have been analysed by this method after removal of I- by resin dialysis.


Production and evaluation of antibodies for radioimmunoassay of secretin.

In order to produce antibodies for radioimmunochemical analysis of secretin in plasma, 16 rabbits were immunized; two different immunization schemes were followed. All rabbits produced detectable antibodies to secretin. The final dilution of the antisera necessary to bind 50% of 5 fmol [125I]secretin varied from 1:5,000 to 1:2,300,000. The avidity of antisera, expressed by the equilibrium constant, ranged from 5 x 10(6) 1 x mol-1 to 3 x 10(11) 1 x mol-1. Six rabbits produced antisera that displayed avidity sufficient for measurement of the physiologic concentrations of secretin in plasma (Keff greater than 10(11) 1 x mol-1). The equation of Sips was used to evaluate the heterogeneity of the antibodies. Seven of the 16 antibodies to secretin had a heterogeneity index of 0.90 or more. Cross-reactivity with structurally related peptide hormones (glucagon, vasoactive intestinal peptide, gastric inhibitory peptide) was found to be negligible for the six antisera examined (those with the highest avidity). Three of the high-avidity antisera were examined for reactivity with secretin fragments. They all bound the C-terminal secretin tricosa and tetradecapeptides almost as well as pure natural secretin, whereas the reactivity with the N-terminal tetradecapeptide was slightly lower.


Folic acid binding by human plasma albumin.

Binding of [3H]folate to pure human plasma albumin was studied by Sephadex G-200 gel filtration in a steady-state system. The experiments showed the presence of two binding sites per molecule of albumin and an equilibrium constant of 0.9x10(3) 1/mol. With normal human plasma, only albumin bound exogenous [3H]folate with nearly the same equilibrium constant. In human blood plasma at concentrations of less than 10(-5) mol/1, 50% of folate was free, and 50% was bound to albumin. Binding was maximal at about pH 6 and negligible above pH 8 and below pH 4.5. Neither human transferrin nor Cohn fraction II was able to bind [3H]folate.


The development of puberty, the sexual début and sexual function in hypospadiacs.

The development of puberty, the sexual debut and the sexual function were investigated in a longitudinal study of an unselected material of 220 primary cases of hypospadiacs, treated during the period 1965 to 1969 and followed-up during the period 1965 to 1974. The development of puberty in hypospadiacs strongly resembled that in a normal male population. Out of 121 hypospadiacs between 13 and 30 years of age 66 had had sexual intercourse. The median age for the sexual debut was 16.9 years compared to 16.6 years in a normal male population. Thirty out of 55 hypospadiacs without experience of sexual intercourse were in the age-group 13-16. Hypospadiacs with experience of sexual intercourse continued their sexual function was normal. Forty-one out of 66 were married and 24 out of 41 had children. In order to study the influence of the surgical treatment on the sexual debut and sexual function the 121 hypospadiacs were divided into two groups: those in whom treatment was completed before or at the age of 12 years, and those in whom treatment was completed at 13 years of age or later. The median age for the sexual debut was 15.5 years in the former group and 17.6 in the later group. An interesting finding was that almost half of the hypospadiacs in whom treatment was complted at 13 years of age or later had had a preoperative sexual debut despite the presence of curvature in all cases, and despite the fact that all types of hypospadias were represented. The median age for the sexual debut in this group was 17.1 years.


Intraneural tissue reactions induced by internal neurolysis. An experimental study on the blood-nerve barrier, connective tissues and nerve fibres of rabbit tibial nerve.

Surgical treatment of peripheral nerve lesions associated with intraneural fibrosis is sometimes extended to include internal neurolysis. This procedure is performed in order to release the individual nerve fascicles from interfascicular scar tissue which is believed to constrict nerve fibres and thereby interfere with their function and regenerative capacity. However, an internal neurolysis per se implies a significant trauma to the nerve and may induce microvascular damage and formation of new intraneural scar tissue. Considering this, such a procedure appears justified only when the preoperative intraneural fibrosis is more severe than the scarring which might be induced by the surgical procedure as such. In order to evaluate the tissue reactions following internal neurolysis an experimental investigation was carried out: internal neurolysis was performed on normal rabbit tibial nerve. After varying postoperative periods up to 6 months specimens of nerves were analysed. Reactive changes of connective tissue and myelin sheath lesions, indicating nerve fibre damage, were investigated in histological sections studied by light microscopy. Barrier function of perineurial membrane and endoneurial vessels was investigated by fluorescent microscopic tracing of locally applied or intravenously injected albumin labelled with Evans' blue. The results indicate that an experimental internal neurolysis per se may induce fibrosis in all layers of the nerve and may cause some nerve fibre damage. However, the barrier function of the perineurium and the endoneurial vessels seems to be generally well preserved. The findings are discussed in relation to indications for internal neurolysis.


Growth of the vomero-premaxillary suture in children with bilateral cleft lip and palate. A histological and roentgencephalometric study.

The significance of the vomero-premaxillary suture (VPS) in mid-facial development in patients with complete bilateral cleft lip and palate (C-BCLP) was evaluated. Histological analysis of the VPS in eight specimens, ranging in age from full term to 22 months, revealed evidence of growth at both sutural borders. Various theories to explain the consistent presence of secondary cartilage, localized mainly to the posterior end of the suture, were assessed. It was considered most likely that the formation of cartilage was promoted by mechanical stresses, set up during a period of rapid growth. Roentgencephalometric data from seven C-BCLP patients (age range: 2-7 months) demonstrated the existence of a true, rather than a relative, premaxillary protrusion. Five patients had metallic implants inserted on either side of the VPS at the time of initial surgery and were followed up roentgencephalometrically to ages ranging from 5 to 36 months. Although continuous growth was recorded in the VPS, there was a post-surgical decrease in the premaxillary protrusion. On the basis of both the histology and roentgencephalometry it was concluded that traumatic surgery involving the VPS would be likely to contribute to the impaired mid-facial growth sometimes seen in operated C-BCLP patients.


A new principle for the cleansing of infected wounds.

When dry porous hydrophilic beads, formed by a three dimensional network of dextran polymers, are placed on a discharging wound, they absorb the exudate and swell to form of a gelatinous layer. Within this gelatinous layer a separation of substances occurs according to their molecular weights, with the smaller (MW less than 1000) freely penetrating the pores of the beads and the larger (MW greater than 5 000) remaining in the interspaces. Since proteins are removed from the wound surface with the fluid, crustformation on the wound is prevented. Clotting within the gel layer does not occur, since, as shown in another study (Aberg, Hedner, Jacobsson & Rothman 1976), wound exudate contains a high amount of fibrin-fibrinogen split products and no coagulable fibrinogen. Therefore as long as dry beads are available, exudate can be sucked up. With the wound exudate bacteria, degradation products and toxins are removed from the wound surface. A substance with the above described properties Debrisan (Pharmacia AB, Sweden) was used to treat various types of wounds. The treatment was most effective for profusely discharging infected wounds. Within a few days inflammation subsided, exudate decreased and granulation tissue appeared. So far no side effects are observed and even patients, who during years of treatment of leg ulcers had become sensitized to most dressings and local antibiotics could be treated. The new technique for sampling of wound fluid also offers a model for studies on inflammatory mediators and protein loss.


Osteoma of the mandibular condyloid process. Case report.

The incidence of true osteoma in the mandibular condyloid process is extremely rare. An unusual case in a 35-year-old man with a classic picture of facial asymmetry is reported. Because of the microscopic similarity of benign osteogenic neoplasma and the hyperplastic overgrowths, the diagnosis of osteoma is sometimes difficult. We believe that the essential differences between an osteoma and an exostosis lie in the location of the overgrowth, the extent of involvement of the condyle, and the age of the patient. Surgical excision is justified because benign tumors of bone do not invariably retain their innocent characteristics.


Recent advances in the drug treatment of the functional psychoses.

Little is known about the primary cause of mental illness but in a major area of psychiatry effective secondary prevention has been developed. Potent psychopharmacological agents have become available to the clinical psychiatrist and it has been shown that the prognosis in the psychoses can be significantly improved when continuous drug treatment is prescribed. As treatment has to be given for years the psychiatric clinic has become committed to a potentially large group of patients whose mental wellbeing is dependent upon regular psychotropic medication.


Urinary oestrogen and plasma human placental lactogen as initial screening tests for a placental sulphatase deficiency.

As a result of routine screening of ante-natal patients by urinary total oestrogens and plasma human placental lactogen (HPL) from 35 weeks, a rare placental sulphatase deficiency was indicated which was later confirmed by in vitro studies of placental enzyme activities.


The natural history of bacterial colonization of the newborn in a maternity hospital (Part II).

The object of this study was to determine the sources from which the newborn infant derives his bacterial flora during the first 5 days after birth. Detailed bacteriological data was obtained from 193 mothers antenatally and during labour, and from their infants on the day of birth and on Day 5. Organisms were typed by appropriate methods and the 193 mother-baby pairs declared to be a 'match' or a 'non-match' according as to whether or not identical bacteria were isolated from both members of the pair. Weekly swabs from hands and noses of staff were taken throughout the 12 months of the study. Swabs were also taken from the environment and air samples from different areas in the hospital. In approximately one third of infants the colonizing bacteria are derived from their mothers, in over 70 per cent of instances from the mother's rectum. The mother's birth canal is not a common source of bacteria and there is no direct relationship with the noses or hands of staff. Artificial feeds are not a source of the colonizing bacteria. The overall distribution of the bacterial species in the infants differed from that found in the hospital environment but this does, none the less, constitute a reservoir of bacteria which is being continually replenished from human sources. Pathogens such as Staph, aureus and Strep. pyogenes are no longer commonly found in newborn infants in the modern maternity hospital, but the need for continual vigilance and an efficient bacteriological service in all maternity units has been in no way diminished.


Plutonium hazard in respirable dust on the surface of soil.

Plutonium-239 in the fine particulate soil fraction of surface dust is subject to suspension by air currents and is a potential health hazard to humans who may inhale it. This respirable particulate fraction is defined as particles less than or equal to 5 micrometers. The respirable fraction of surface dust was separated by ultrasonic dispersion and a standard water-sedimentation procedure. Plutonium concentration in this fraction of off-site soils located downwind from the Rocky Flats Nuclear Weapons Plant (Jefferson County, Colorado) were as much as 380 times the background concentration. It is prposed that this method of evaluation defines more precisely the potential health hazard from the respirable fraction of plutonium-contaminated soils.


Screwworm eradication: inadvertent selection for noncompetitive ecotypes during mass rearing.

The rapid fixation of a rare allelic form of alpha-glycerol phosphate dehydrogenase is related to a loss of competitive ability in nature of factory-reared screwworm flies. The increase in frequency results from selection for survival under conditions of domestication and rapid development at high constant temperatures in the factory.


Side chain metabolism of 25-hydroxy-[26,27-14C] vitamin D3 and 1,25-dihydroxy-[26,27-14C] vitamin D3 in vivo.

Radioactive CO2 was detected in expired air after the administration of 25-hydroxy-[26,27-14C] vitamin d3 to vitamin D-deficient hypocalcemic rats; 14co2 was also detected after the administration of 1,25-dihydroxy-[26,27-14C] vitamin D3 to rats raised on the same diet. Nephretcomy totally abolished 14CO2 formation after administration of 25-hydroxy-[26,27-14C] vitamin D3 but not after the administration of 1,25-dihydroxy-[26,27-14C] vitamin D3. The production of 14CO2 commenced within 4 hours after injection of 1,25-dihydroxy-[26,27-14C] vitamin D3, suggesting a possible relevance of this reaction to the function of 1,25-dihydroxyvitamin D3. These results at least demonstrate a new metabolic pathway of vitamin D3 metabolism involving the oxidation of a portion of the side chain of 1,25-dihydroxyvitamin D3 to CO2.


Elevated plasmz zinc: a heritable anomaly.

An extremely high concentration of zinc in the plasma (hyperzincemia) was found in five out of seven members of one family and in two out of three second generation indiviuals, an indication that the condition is heritable. The excess zinc in the plasma appears to be bound to serum proteins, with no apparent clinical symptoms or abnormalities.


Markers for detection of supplementation in narcotic programs--deuterium-labeled methadone.

Specific deuterium labeling of methadone and use of gas chromatography-mass spectroscopy technique permits rapid and quanitative determination of the ratio of the labeled to unlabeled drug in body fluids. A trideuertiomethadone (methadone-d3) was shown to have exactly the same analgesic activity and toxicity in mice as methadone. The rates of absorption, distribution, and excretion of methadone-d3 and methadone were identical in rats. These observations suggest that methadone-d3 may be used as an in vivo marker for monitoring methadone intake of patients, and thus may improve the effectiveness of methadone treatment programs.


A multistable movement display: evidence for two separate motion systems in human vision.

Two competing sensations of apparent movement were produced by the rapid alternation of two multielement stimulus frames. Either sensation could be made dominant by, appropriate manipulations of the stimulus display. The results suggest that there are two systems capable of generating movement signals in man. One system depends on preliminary processing of form, and the second system does not.


Constancy and uniqueness in a large population of small interneurons.

The anatomy of 61 of the smallest interneurons in the brain of the locust shows the same tendency toward uniqueness, contancy of neuropil abortizations, and frequency of occurrence of supernumerary cells as does that of 17 large interneurons; the size and number of neurons thus have no obligatory relation to the concept of the unique identifiable neuron.


Abolition of direction selectivity in the visual cortex of the cat.

Cats were reared in a stroboscopically illuminated environment, which deprived them of expereience with visual movement but allowed them form vision. In these cats, neurons of the visual cortex displayed normal orientation selectivity, but direction selectivity was virtually abolished. The effect remained unaltered by long periods of normal visual exposure.


Studies of regional myocardial blood flow: results in patients with left anterior descending coronary artery disease.

Measurements of regional myocardial blood flow have been performed rapidly and safely in man at the time of coronary arteriography. Xenon-133 was injected into the coronary artery and estimates of myocardial capillary perfusion were made by computer analysis of the multiple precordial tracer washout curves recorded with a scintillation camera. Blood flow rates/100 g/min in different areas of the heart were calculated by the Schmidt-Kety formula, using an assumed partition coefficient, and were related to the coronary vascular lesions by landmarks provided by the arteriograms. The flow significance of lesions was assessed by making measurements at rest and during interventions that increase coronary blood flow. Perfusion was also estimated in areas supplied by collateral vessels, and regions of scar were detected from the initial distribution of peak tracer activity. In patients with less than 50% obstructions apparent on coronary arteriograms and in those with greater than 50% isolated left anterior descending lesions average mean left ventricular (LV) myocardial perfusion values were not reduced below values found in patients with normal coronary arteries and normal cardiac function. However, in patients with significant two-vessel disease (LAD + right, LAD + circ) mean LV perfusion was significantly reduced. Average regional myocardial perfusion distal to significant lesions was not selectively reduced below the remainder of the ventricle unless the lesions were 100% obstructions. However, both total and distal regional myocardial perfusion increased less in 12 patients with greater than 50% lesions than in 12 others with normal arteriograms or less than 50% lesions. Subnormal flow responses in all of the former group were associated with angina pectoris compared with no angina in the latter. The studies indicate the potential utility of the measurements of regional myocardial blood flow in the evaluation of patients with ischemic heart disease who are potential candidates for myocardial revascularization procedures.


Adverse reactions to radiopharmaceuticals.

This review covers the side effects and adverse reactions to radiopharmaceuticals that were reported in the literature over the past 25 years. The information published prior to 1970 is sporadic, but due to the increased utilization of nuclear medicine procedures and the recognition that radiopharmaceuticals may have pharmacologic side effects, a registry has existed since 1971 to tabulate information on such effects. This survey is medical, rather than pharmaceutical in emphasis and so the adverse reactions are classified according to the target-organ systems involved rather than according to the specific radionuclides or to pharmaceuticals. If any of the radiopharmaceuticals of present or past use are not mentioned in this review, it is because no reports on their side effects were retrived by us. Hopefully, the organized registry system suggested by the Society of Nuclear Medicine (SNM) will enable a more complete recording of side effects from radiopharmaceuticals in the future.


Anesthetic technic using profound hypothermia for correction of congenital heart defects in infants and small children.

Profound hypothermia can be a useful adjunct in the intraoperative management of infants and small children undergoing surgical correction of congenital heart defects. A case description of a 5 1/2-month-old male infant with total anomalous pulmonary venous drainage who had successful repair using surface cooling, cardiopulmonary bypass, and pump cooling to 20 C with intermittent periods of low systemic blood flow illustrates the technic. Discussed are the value of surface cooling before cooling on cardiopulmonary bypass, physiologic changes affecting the intraoperative and postoperative course, and the major risks and advantages of the technic.


A perspective focus on the indicated surgical treatment of resistant clubfoot in the infant.

Ligamentous contracture is the chief factor in maintaining clubfoot deformity. Precise plans of segmental ligamentous release are called "selective segmental syndesmotomies." Critical segmental assessment by roentgenograms is required to choose the proper syndesmotomy. Proper early correction of resistant subtalar and midtarsal deformity by selective segmental syndesmotomy can solve much of the persistent trouble confronting the surgeon.


The sexually exploited child.

Sexual exploitation of children (under 14 years of age) is a common occurrence, although actual numbers are unknown. There are three major forms of sexual abuse: (1) incest, ie, sexual activity between consanguineous family members; (2) sexual assault, such as rape or molestation by adults not related to the child; and (3) habitual sexual exploitation for purposes of financial reward or perverse sexual satisfaction. Brother-sister incest has the highest incidence in the middle and upper socioeconomic levels and is probably the least damaging, psychologically, to sexual adjustment later in life. Father-daughter incest is more common in the lower socioeconomic levels and is thought to produce  major disorders in the psychosexual area. Sexual assault of children, if handled supportively and with understanding by the surrounding adults, including parents, physicians, teachers, law enforcement officers, and others, can result in minimal sequelae; however, often the situation is handled with emotional reactions ranging from disgust to hysteria which result in the child's being victimized and traumatized unnecessarily. These latter situations lead to sexual acting-out in adolescence, promiscuity, perversions, or frigidity in adult sexual life. Teachers, physicians, and child welfare workers need to be attuned to the possibility to sexual abuse in the children they serve.


The effect of food on procainamide absorption.

The effect of food on the absorption characteristics of procainamide was assessed after oral administration of the drug to eight male patients in the fasting and postprandial states. Serum concentration-time curves showed no significant difference in peak serum levels of procainamide, in the time the peak value was reached, or in the area under the serum concentration-time curves, indicating the total amount of procainamide present in the serum. The bioavailability of procainamide appears not to be significantly altered by taking an oral dose with food.


Plantar neuroma: analysis of results following surgical excision in 145 patients.

Few series deal with the long-term results of surgical exision of plantar neuromas. The results of a study with a 21.5 month average follow-up are presented. Of 145 patients undergoing surgery from 1970 to 1973, 85 returned for examination and roentgenograms. There were 13% with unsatisfactory results and 21.3% with some pain remaining. Caution should therefore be used in assuring patients of complete relief.


Sporotrichosis: an unusual disseminated cutaneous case and a fatal pulmonary case.

Two unusual cases of sporotrichosis are presented. One patient had disseminated vesicular skin lesions which yielded Sporothrix schenckii on culture. The other, with extensive pulmonary sporotrichosis, continued to have sputum cultures positive for S schenckii during three years of intensive chemotherapy.


Indications for and results with the Swanson distal ulnar prosthesis.

Classically, wrist synovectomy, when the distal radioulnar joint is involved, includes excision of the distal ulna (the classical Darrach procedure). Orthopedists and rheumatologists are well aware of the propensity for extensor tendon rupture, particularly of the ring and little finger, in this area. Dr. Alfred Swanson has presented his results with a silastic interposition to substitute for the excision of the distal ulna. This paper presents a surgical technic, indications, and results in five cases of rheumatoid arthritis in which wrist synovectomy and repair of extensor tendon ruptures were done as appropriate. This distal ulnar prosthesis is recommended for routine use in wrist synovectomy when excision of the distal ulna is performed.


Nephropathy caused by methicillin therapy for staphylococcal septicemia.

Nephropathy, eosinophilia and fever were observed in an 18-year-old man being treated for staphylococcal septicemia. Parenteral challenge with suspected sensitizing agents confirmed methicillin as the likely offender. Review of the literature relating to methicillin-induced nephropathy suggests a hypersensitivity origin for this disorder, but immunologic and ultrastructural investigation to date has failed to elucidate pathogenesis.


Genitourinary complications of abdominoperineal resection.

The genitourinary complications of 86 consecutive cases of abdominoperineal resection at the University of Oklahoma Health Sciences Center are described. Vesical dysfunction was the most common problem, occurring in 11 patients in our series. Eight required prostatectomy for urinary retention. The significance and treatment of vesical dysfunction is somewhat controversial, but an attempt to document the cause should be made in every case. Voiding symptoms and results of intravenous urogram with postvoiding films, cystogram, cystometrogram, and cystoscopy are diagnostically pertinent. Accordingly, preoperative urologic evaluation is indispensable to proper treatment of rectosigmoid carcinoma.


Hyperkalemia and acidosis in lead nephropathy.

Defective potassium excretion with clinical acidosis, associated with fixed moderate sodium wasting, has been found to be a common abnormality in lead nephropathy. Lead poisoning has been shown by others to be associated with depression of the renin-aldosterone system and of sodium and potassium activated adenosinetriphosphatase (ATPase). Since these hormonal defects may contribute to the hyperkalemia and are reversible, lead poisoning should be treated aggressively. Management also requires proper regulation of dietary sodium, correction of acidosis, limitation of dietary potassium, and minimal use of antihypertensive agents, as well as the administration of allopurinal for urate control.


The oxytocin challenge test.

In a group of 152 high-risk pregnancies, 266 oxytocin challenge tests were reviewed. There were 137 patients with persistently negative oxytocin challenge tests with only one false-negative test being recorded. Fifteen patients who displayed a positive test at some time in their antepartum course are discussed along with other aspects of the oxytocin challenge test.


Fat embolism revisited.

Despite continuing interest in fat embolism, the precise pathogenesis and the best treatment of the syndrome are still in doubt. To assess the effect of a high index of suspicion about the outcome of the syndrome, we have compared 37 patients seen from 1962 to 1968 with 16 patients seen from 1968 to 1974. The study of the original group of patients generated considerable interest in the diagnosis and management of the syndrome at our institution. The two groups are well matched for age, sex, and source of injury. The more recent group (1968-1974) seemed to have had more severe injuries as judged by number of fractures and need for blood transfusions. Despite this increase in severity of injury, the mortality rate for the period 1968-1974 was only 12.5% as opposed to 21% for the period 1962-1968. This improvement in mortality was achieved without resort to many of the popular pharmacologic regimens, including steroids and heparin. A high index of suspicion leading to an early diagnosis of respiratory dysfunction and aggressive supportive therapy has been responsible for the improved results.


Septic arthritis and Reiter's syndrome in sickle cell disorders: case reports and implications for management.

Two patients with sickle cell disorders developed gram-negative septic arthritis and responded poorly to conventional managment. Unfavorable factors included (1) confusion with the nonseptic arthropathy of a sickle crisis; (2) impaired articular perfusion, perhaps related to local sickling; (3) conversion of an infecting organism to an L-form in the presence of cell-wall inhibitors; and (4) interference with cultures and antibacterial titrations of synovial fluid caused by intro-articular administration of antibiotics. Prolonged treatment with very high doses of antibiotics was required to eradicate infection in both patients. Because sickling and local hypoxia apparently interfere with defenses against infection, anemia should be corrected by transfusion. One patient had had Reiter's syndrome; the dysenteric form of this disease may be a cause of arthritis in some sicklemic patients.


Laryngeal neoplasm mortality in Oklahoma: 1950-1970.

A survey of death certificates of victims with laryngeal cancer in Oklahoma for the period 1950 to 1970 attempts to corroborate findings of the current literature. Sex-race specific death rates per 100,000 for white, nonwhite, and American Indian populaces displayed a distinct sex and racial pattern: respectively, 38.52, 28.11, and 12.52 for males; 5.25, 1.23, and 0 for females. Age-adjusted death rates per 100,000 for white males for the four consecutive five-year periods were 19.00, 21.64, 20.91, and 26.81; these rates show constant mortality for laryngeal cancer for the period between 1950 and 1965, followed by an increase of approximately 30% in the 1966 to 1970 interval. Similar analysis of the white females, nonwhite males, and nonwhite females did not reveal such a clear secular pattern, although the adjustment for age did preserve the sex and racial pattern indicated above. Age-adjusted laryngeal cancer death rates of 42.34, 46.14, and 48.51 for the rural, nonmetropolitan, and metropolitan counties, respectively, indicated a direct association between mortality and degree of urbanization. All findings appeared to be in concordance with those given in the recent literature.


Routine magnification cerebral angiography: a practical system designed for community hospital application.

Magnification cerebral angiography is no longer to be considered a tool only of clinical investigation; its routine application is clearly advantageous. A relatively inexpensive system has been developed which can be applied in a special procedure suite where cardiac and abdominal angiography as well as other radiographic procedures must be performed.


Nephrolithiasis: recent advances in therapy.

The stone-forming process includes crystal formation, crystal aggregation, and retention time to allow growth. The crystal-forming process, in turn, is influenced by the pH of the urine, the solute load, and inhibitors of crystallization. Idiopathic stone disease is characterized by recurrent formation of calcium oxalate, calcium phosphate, and hydroxyapatite stones without an apparent underlying cause. Treatment of idiopathic stone disease has been aimed at decreasing the solute concentration, increasing the solubility of calcium phosphate, or interfering with extension of the crystal lattice.


The augmentive use of methyl methacrylate in the management of pathologic fractures.

Methyl methacrylate is a useful adjunct to obtain secure internal fixation in the treatment of comminuted pathologic fractures. This method was used in 73 patients with 81 pathologic fractures of whom only four failed to regain function in the extremity which was operated upon. While it is probable that methyl methacrylate may have an adverse effect on fracture healing, the fixation achieved when applied to only one surface appears adequate and was observed to last for as long as nine years. The use of methyl methacrylate to augment internal fixation of pathologic fractures offers the patient a better chance to return to normal activities than any of the methods that are in use to date.


The surgical and hematologic significance of accessory spleens.

The approximately 10 per cent incidence of accessory spleens in the general population is well documented, and accessory spleens often are not clinically significant. Trauma, torsion and, especially, hematologic diseases can affect an accessory spleen. A careful search should be made for accessory spleens, and they should be removed at the time of primary splenectomy so as to avoid a second operation later in life.


Prognostic signs and nonoperative peritoneal lavage in acute pancreatitis.

Three hundred patients with acute pancreatitis have been studied. Pancreatitis was associated with alcoholism in 207, biliary tract disease in 51 and other conditions in 42. Twenty-two patients died, and an additional 34 patients required more than one week of treatment in the intensive care unit. Retrospective analysis of the first 100 patients identified 11 objective findings which correlated with the occurrence of serious illness or death. They were, on admission, age over 55 years, blood glucose level over 200 milligrams per cent, white blood count over 16,000 per cubic millimeter, serum lactic dehydrogenase level over 350 International units per liter and serum glutamic-oxalacetic transaminase level over 250 Sigma Frankel units per cent. During the initial 48 hours of therapy, the findings were hematocrit value decrease over 10 percentage points, serum calcium level below 8 milligrams per cent, base deficit over 4 milli-equivalents per liter, a blood urea nitrogen level increase over 5 milligrams per cent, estimated fluid sequestration over 6 liters and arterial oxygen tension less than 60 millimeters of mercury. Prospective application of these signs in the latter 200 patients permitted the accurate early identification of those with severe pancreatitis. Only one of 162 patients with fewer than three of these early features was seriously ill or died, while 24 of 38 patients with three or more early positive findings were seriously ill or died. The objective early identification of patients with severe pancreatitis permits more vigorous management of this group and also provides a basis for the selection of patients for the evaluation of proposed improved therapies. Percutaneous peritoneal dialysis in severe pancreatitis was evaluated in ten patients, with three or more positive early signs, who were randomly assigned to dialysis or continued conventional care. Morbidity was strikingly reduced in patients who underwent dialysis, and while death or more than nine days of intensive care occurred in two of five patients who did not receive dialysis, all five patients having dialysis recovered after fewer than nine days of intensive care treatment. Serious illness or death occurred in 31 of the first 100 patients but in only 26 of the more recent 200 patients. There has been a similar fall in mortality from 15.0 to 3.5 per cent. Factors which may contribute to this improvment include the objective early identification of patients with severe disease, the avoidance of early laparotomy whenever practical, the prolongation of nasogastric suction until all evidence of pancreatic inflammation has resolved, careful monitoring of respiratory function and early treatment of pulmonary complications and peritoneal dialysis in patients with severe disease.


Collagen metabolism in infected colonic anastomoses.

Infection of the peritoneum has an adverse effect on the healing of colonic anastomoses. It has been suggested that infection results in a disturbance of colonic collagen metabolism, but the precise nature of the biochemical disorder is uncertain. Colonic collagen metabolism was studied in infected anastomoses in the left colon of rats. The rats were labeled with radioactive proline from an early stage of growth, and infected anastomoses were compared with anastomoses of the control group of uninfected rats. Infection resulted in significant changes in collagen metabolism during the early phase of colonic healing. There was a significant reduction in the amount of salt soluble collagen in infected anastomoses on the third postoperative day compared with anastomoses of the control group, and reduced amounts of acid soluble collagen and insoluble collagen were found in infected anastomoses on the seventh postoperative day. These observations suggest that the defective healing of infected colonic anastomoses results either from an increased lysis of newly formed--salt soluble--collagen or from a reduction in the intracellular formation of collagen.


The lymph nodes of the porta hepatis.

The area under the liver was dissected in 27 human autopsy specimens to search for lymph nodes in the fissures. Nodes were present in all instances. They were in the transverse fissure, posterior to the portal vein, posterior to pars transversus of the left portal vein and associated with the left hepatic artery. The size varied from 2 millimeters to 2 centimeters. Each node was histologically confirmed. Nodes were infrequent and small on the right. Nodes were not found between the portal vein, hepatic artery and bile ducts in the fissures. Nodes were found outside the fissures in the fascia between the bile duct and hepatic artery. Occlusion of the portal vein and hepatic artery could be expected before occlusion of the bile duct. Node enlargement in the transverse fissure is anticipated as a rare cause of jaundice.


Correlation of neurologic complications and pressure measurements during carotid endarterectomy.

There was no significant difference between the mean occluded internal carotid artery pressure in asymptomatic, transient ischemic attack or prior stroke patients. The stump pressure was not consistently elevated at the second operation in those having undergone bilateral procedures. Estimate of back bleeding from the internal carotid artery operation did not necessarily correlate with the stump pressure. Adequate back bleeding was recorded in patients with a low stump pressure, and reduced bleeding was noted in individuals with a high stump pressure. The pressure gradient across the stenosis of the bifurcation of the carotid artery was helpful in assessing the degree of stenosis present. The occluded internal carotid artery pressure seemed to be a helpful aid in indicating those patients with poor collateral flow and, therefore, at high risk of ischemic brain damage. The use of an inlying shunt in those individuals having a low stump pressure may be expected to reduce the over-all neurologic complication rate in patients undergoing carotid endarterectomy.


The morbidity of vasectomy.

Elective bilateral vasectomy has become an established surgical procedure to achieve sterilization in the male. The ability to accomplish this by an ambulatory technique, with few side-effects, probably accounts for the widespread demand by the general public. However, a number of significant complications were encountered in a series of 250 patients who were carefully surveyed to determine the actual morbidity of this operation. In addition, five patients exhibited spontaneous regeneration of the severed vas deferens, one instance having been documented as occurring after the absence of spermatozoa from the ejaculate. These difficulties must be emphasized in preoperative discussions with patients seeking this method of contraception.


A study of autopsies upon 116 patients with acute pancreatitis.

A series of 116 nonselected and consecutive patients with acute pancreatitis with a fatal outcome underwent necropsy and have been analyzed with special attention paid to hepatic findings and the cause of death. This series includes the total fatalities caused by the disease during a 15 year period from 1956 to 1970. All but two patients died in the first attack of acute pancreatitis. The patients were divided into four etiologic groups: gallstone disease, 43 per cent; alcoholism, 25 per cent; idiopathic origin, 18 per cent, and postoperative origin, following abdominal operations, 14 per cent. Over the three five-year periods, the frequency of alcohol abuse as a predisposing factor increased, while gallstone disease showed a corresponding decrease. About 75 per cent of the patients had hyperbilirubinemia. Half of these showed signs of cholestasis. Macroscopic steatosis of the liver was recorded in 62 per cent of the alcohol addicts and in about 25 per cent of the patients in the other etiologic groups. Shock and late sequelae of shock were the dominating immediate causes of death in 72 per cent. About 50 per cent of the fatalities occurred within the first week. Most of these early deaths were caused by intractable circulatory failure. Early death was most commonly caused by alcoholism, followed in frequency by gallstone disease. It is possible that impaired hepatic function contributes to the fatal outcome in both early and late phases of the disease.


The role of scalene lymph node biopsy in advanced carcinoma of the cervix uteri.

Considerable controversy exists in the role of scalene lymph node biopsy in the pretreatment assessment of patients with carcinoma of the cervix uteri. Scalene lymph node biopsy was carried out on ten patients having advanced carcinoma of the cervix uteri with documented para-aortic nodal involvement. Metastatic carcinoma was found in the scalene lymph nodes in five of ten patients. These preliminary findings suggest that excision of scalene lymph nodes should be carried out prior to the institution of therapy in all patients with carcinoma of the cervix uteri which is metastatic to the para-aortic lymph nodes.


Unimpaired renal, myocardial and neurologic function after cross clamping of the thoracic aorta.

Twelve patients who had sustained trauma presented at the emergency department with either asystole or profound hypotension. All underwent thoracotomy and temporary cross clamping of the descending thoracic aorta as part of the resuscitative measures; all received massive amounts of fluids and cold blood and underwent prompt surgical intervention. In none of these patients was there evidence of myocardial, peripheral nerve, neurologic or renal damage. One patient had residual cortical blindness. Measures were taken to preserve renal function before, during and after aortic cross clamping. These included the avoidance of nephrotoxic antibiotics, limit of clamping time to the minimum effective period, intermittent release of the aortic clamp, and intraoperative administration of osmotic diuretics or furosemide, or both. Other factors which may have contributed to these results were the youth of these patients, the absence of cardiac, renal or metabolic diseases and the hypothermia resulting from the administration of large amounts of cold blood. We concluded that temporary cross clamping of the descending thoracic aorta should be performed only for patients with massive exsanguine trauma who have cardiac arrest or who do not respond to other intensive resuscitative measures.


Elemental diet and bile induced pancreatitis.

The effectiveness of an elemental diet was investigated as both a prophylactic and therapeutic agent in experimental canine pancreatitis. Pancreatitis was induced by operative injection of a bile -saline solution mixture under pressure retrograde into the main pancreatic duct. In addition to a preinjection control sample, serial biopsies were obtained at 30 minute intervals for 90 minutes after injection and fixed for light and electron microscopic examinations. In addition, preoperative and postoperative blood samples were drawn and analyzed for amylase. After operation, half of the dogs from each original group were fed Vivonex-100, the other half from each group, regular laboratory chow, yielding four ultimate groups based on preoperative and postoperative diets. Successful induction of pancreatitis was evaluated by the difference between preoperative and postoperative amylase values, all of which were significant by group at the p less than 0.01 level. No ultrastructural evidence was found for the modification of zymogen granules with the pretreatment elemental diet nor were differences evident, histologically or ultrastructurally, in the severity of pancreatitis between the pretreated and nonpretreated groups. Finally, gross mortality figures demonstrated no efficacy of elemental diet for pretreatment prophylaxis of acute pancreatitis.


Surgical treatment of partial extraluminal occlusion of the vertebral artery.

Twenty-three patients with insufficiency of the vertebral artery due to partial extraluminal occlusion of a segment of the first part of the vertebral artery were operated upon with postoperative symptomatic improvement. Selection of patients is dependent on angiography of the aortic arch with visualization of the vessels of the neck. There was no mortality and no significant morbidity among these patients.


An electron microscopic study of the distribution of sodium in normal, pentagastrin-stimulated and secretin-inhibited fundic mucosa of the stomach of the rat.

Normal, pentagastrin-stimulated and secretin-inhibited stomachs of rats were fixed either by perfusion or by immersion in an unbuffered osmium tetroxide potassium pyroantimonate mixture at a pH of 7.6, and the mucosa from the fundic area was examined under the electron microscope for sodium localization. Both fixation methods gave comparable results. In the control tissue, sodium pyroantimonate crystals were mainly seen in and around the collagen fibers in the interstitium and to a lesser extent in the basal and lateral plasma membranes of the epithelial cells. No significant differences were noticed in the secretin-inhibited tissue. In contrast, in the pentagastrin-stimulated mucosa, an increase in the amount of precipitate along with a redistribution occurred. The pyroantimonate technique seems promising for studying the mechanism of sodium transport in the gastric mucosa.


A modified technique for the reconstruction of the alimentary tract after pancreatoduodenectomy.

The high death rate for those patients undergoing pancreatoduodenectomy, which is a result of leakage of biliary and pancreatic anastomoses in most instances, justifies the study of this technique for rebuilding the alimentary tract. The use of two separate intestinal loops for the biliary and pancreatic anastomoses is the basis of this method. This technique reduces the morbidity and the death rates which are the result of leakage in either anastomosis because it separates biliary and pancreatic fistulas.


Intra-abdominal control of incidental indirect inguinal hernia.

A technique for dealing with incidental inguinal hernias during the course of other abdominal operations has been used on six patients in the past four years and kept the hernias reduced through the immediate postoperative period.


Further evidence for an intestinal phase hormone that stimulates gastric acid secretion.

The studies described in this report were directed at isolating the hormone responsible for the intestinal phase of gastric acid secretion. One hundred and ten extracts of hog intestinal mucosa, each representing the yield from about 3,000 hogs, were prepared by a method for isolating small peptides that involved heating, absorption on diethylaminoethylcellulose (DEAE), and acid precipitation. All extracts stimulated gastric acid secretion in acute gastric fistula rats, and 56 were highly active according to stringent criteria that required a greater than 50 percent increase in acid output above basal in at least 60 percent of rats. Increasing doses of extract stimulated increasing acid production according to a regular dose-response relationship. Twelve highly active extracts were tolerated without side effects when infused into dogs with Heidenhain pouches and produced a mean 22 fold increase in acid output above basal. The gastrin content of 73 extracts, measured by radioimmunoassay in two independent laboratories, averaged 5,80 ng. per rat dose of extract, which is approximately 1/500 of the minimal stimulating dose of hog gastrin. No extract contained sufficient gastrin to produce an acid secretory response. Administration of the extract together with a maximal stimulating dose of pentagastrin in rats significantly augmented the maximal acid secretory response. Finally, comparison of the acid secretory response to portal and systemic intravenous infusion of the extract in acute gastric fistula rats demonstrated significant inactivation by passage through the liver, in contrast to the results of similar studies of hog gastrin. It is concluded that the extract had all of the known physiologic properties of the intestinal phase hormone and very likely contained the intestinal phase hormone.


The definitive value of active-specific immunotherapy for experimental carcinoma of the colon.

Active-specific immunotherapy with concanavalin A or with neuraminidase-modified syngeneic tumor cells has been studied in an experimental model of colon cancer. Systemic immunotherapy with concanavalin A-modified tumor cells or with neuraminidase-modified tumor cells has resulted in up to 70 percent cure of rats receiving a lethal inoculum of tumor in a model tumor system which otherwise proved 80 percent lethal to untreated hosts. The possible mechanisms whereby neuraminidase or concanavalin A are effective cell-surface modifiers for active-specific immunotherapy are discussed. In vitro studies suggest markedly heightened antigenic recognition following immunization with concanvalin A-modified syngeneic tumor cells. These studies represent the first apparent evidence for the definitive value of systemic active-specific immunotherapy for the adjuvant treatment of large bowel cancer.


Changes in hepatic bile secretion following cholecystectomy.

The volume and compositon of hepatic bile was studied in anesthetized dogs before and approximately 18 weeks after cholecystectomy. Dogs had common duct cannulation, cystic duct ligation, and temporary occlusion of the pylorus. An intravenous infusion of sodium  taurocholate, 9 muEq per minute, was given throughout the experiment. Bile volume, electrolyte composition, bile salt output, and 14C-mannitol clearance were determined during infusion of sodium taurocholate alone and after addition of secretin, 4 U. per kilogram per hour, to the infusion. Cholecystectomy then was done and the same experiment was repeated 18 weeks later. Cholecystectomy significantly increased bile volume, sodium and chloride output, and 14C-mannitol clearance both in response to taurocholate alone and to taurocholate plus secretin. Bile salt output and bicarbonate output were unchanged. The study shows that cholecystectomy significantly alters the volume and composition of hepatic bile. The data indicate that cholecystectomy does not affect ductular function or hepatic secretion of bile salts but that canalicular function is altered significantly.


Proteolysis associated with a deficit of peripheral energy fuel substrates in septic man.

Sixteen seriously septic patients were studied to determine whether proteolysis occurred to satisfy a deficit of peripheral fuel, as suggested by out previous experimental observations. Concentrations of glucose, lactate, free fatty acids,and alanine were measured in blood samples from the femoral artery and vein to determine extraction (+) and release (-) by the leg. Simultaneously, cardiac index (CI) was determined by thermal dilution, so that an estimate of uptake or production of fuel substrates could be made from the proportional relationship of cardiac index to peripheral blood flow. Due to the antilipolytic effect of elevated levels of insulin (42 +/- 4 muM per milliliter) in those patients with elevated cardiac indices (4.38 +/- 0.33 L. per square meter per minute), free fatty acid uptake (-0.59 +/- 0.021 mM.) was reduced. In low-flow septic shock (CI, 1.66 +/- .41 L. per square meter per minute), the majority of glucose taken up by the limb was converted to lactate (arterial lactate, 3.14 +/- 0.7 mM.; deltaA-V 0.68 +/- 0.17). Free fatty acid uptake also was impaired in low-flow sepsis. As opposed to fasting, arterial levels and uptake of ketone bodies were insignificant in sepsis. These findings suggest that there is a deficit of peripheral fuel with respect to glucose and fat. That protein is oxidized to fill this deficit is substantiated by the increased alanine release (-0.13 +/- 0.01, -0.33 +/- 0.12 mM.) in the high-flow and low-flow septic groups, respectively, whereas alanine production was three- and fourfold greater than that observed in fasting patients. Enhanced release of alanine reflects the magnitude of oxidation of branched-chain amino acids and accounts for the high rates of gluconeogenesis and proteolysis observed in sepsis.


Adverse effects of jejunoileal bypass on growth and development.

Ninety percent jejunoileal bypass was performed in 20 growing (100 gram) male Sprague-Dawley (SD) and 15 male, genetically obese, growing (125 gram) Zucker "fat rats" (FR). Twenty SD and 15 FR unoperated rats of similar age and weight served as controls. Animals were evaluated for weight gain or loss, complications, and survival. At death (4 months), caliper measurements of long bones, vertebral column, pelvis, and skull were obtained, and brain, liver, spleen, and kidneys were excised and weighed. Liver and gonadal histology were obtained. The "fat fat" was more fragile, with a 20 percent anastomotic leak rate and a 33 percent mortality rate. The mortality rate was 5 percent (SD) and zero in controls. Bypassed animals showed growth retardation with weight of SD rats 31 percent (p less than 0.05) and FR's 19 percent of controls (p less than 0.05). Organ weights (liver, spleen, kidneys) were similar, except for a smaller brain in bypassed rats [SD 1.06 +/- 0.08 to 1.83 +/- 0.08 Gm. control (p less than 0.05), FR 1.2 +/- 0.12 to 1.68 +/- 0.09 control (p less than 0.025)]. Skeletal development was retarded significantly in bypassed rats [vertebral column, 125.9 +/- 3.5 to 138.3 +/- 3.9 mm. in controls (p less than .025); ilium, 39.4 +/- 1.1 to 46.2 +/- 1.5 mm. in controls (p less than 0.05); skull circumference, 20.2 +/- 0.03 to 22.5 +/- 0.05 mm. in controls (p less than 0.025)]. No increase in fatty infiltration of liver was observed. Spermatogenesis was diminished 30 percent (p less than 0.05) in bypassed (SD) animals. The data document significant morbidity and mortality rates, growth retardation, and diminished spermatogenesis in bypassed "adolescent" rats. These results imply that jejunoileal bypass may affect intellectual, skeletal, and reproductive development adversely and question the advisability of these procedures in growing subjects.


Twenty-four hour membrane oxygenation in dogs without anticoagulation.

Is systemic heparinization or heparin-bonded circuitry better than no anticoagulation during 24 hours of cardiopulmonary bypass? We compared blood pressure, coagulation state, oxygenator function, and scanning electron microscopic appearance of the circuits. There were three groups of five dogs each: Group I had no anticoagulants; Group II received systemic heparization; Group III perfusions utilized heparin-bonded circuits. Group I animals all survived, whereas 80 percent (four fifths) in Group II and 20 percent (one fifth) in Group III survived. Arterial pressures were better maintained in Group I as compared to Groups II and III. The coagulation parameters were similar in all groups. Oxygenator function was maintained at normal in all groups. No thrombi were present in any of the circuits following perfusion. The surfaces in Group I had less debris on them compared to Groups II and III. Animals that died had fibrin thrombi present in tissues examined histologically. Systemic heparinization had no advantage over no heparin in this study. The striking similarity of the coagulation state between Groups I and II and better preservation of the surfaces in Group I were unexpected. Heparin-bonded circuits were unsatisfactory when compared to no anticoagulation and systemic heparinization. Additional experiments with various species with and without anticoagulation must be done to determine the best guidlines for human cardiopulmonary bypass.


Does hyperparathyroidism cause hypergastrinemia?

To define the relationship between hyperparathyroidism (HPT) and gastric function, 31 patients with HPT were prospectively studied before and 2 to 25 months after parathyroidectomy. The gastrin response to a standard test meal (STM), the basal acid output (BAO), and the peak acid output (PAO) were determined. Parathormone and calcium were elevated in all patients and returned to normal following parathyroidectomy. The mean fasting gastrin concentration, mean integrated gastrin response (IGR) to feeding, mean basal acid output (BAO), and mean peak acid output (PAO) were not changed by successful parathyroidectomy. There was no significant correlation between gastrin concentration or gastrin response to feeding and gastric acid secretion. Eight of 31 HPT patients had fasting gastrin concentrations above normal preoperatively and remained so postoperatively. Hypergastrinemia in six of these eight patients could be explained by the Zollinger-Ellison (Z-E) syndrome or chronic atrophic gastritis. The hypothesis that peptic ulcer disease seen in some HPT patients is the result of calcium-induced hypergastrinemia causing gastric hypersecretion is not supported by this study.


Relationship between collateral development and renin in experimental renal arterial stenosis.

Lateralizing renal venous plasma renin activity (RVPRA) ratios offer a predictive index of success of revascularization procedures for renovascular hypertension. Reliance upon nonlateralizing renin ratios to reject functional significance of renal arterial stenosis may deny some patients benefit of successful operations. To test the hypothesis that RVPRA ratios revert toward unity coincident with development of collateral circulation to an ischemic kidney, the relationship between development of collaterals and RVPRA was studied in nine dogs after gradual unilateral renal arterial occlusion with a constrictor. Arterial blood pressure and arteriographic measurement of collateral channels, RVPRA, and renal surface index (RSI) were measured before and during the 10-week interval after constrictor placement. RSI measurements, documenting changes in volume of the renal parenchyma, reflected changes in renal blood flow. Arterial pressure increased in each animal (p less than 0.0009). The number of collateral vessels to the constricted kidney increased with time (p less than 0.01). During the 4 weeks following placement of the constrictors, RSI ratios (constricted: nonconstricted) decreased (p less than 0.003) and RVPRA ratios (constricted: nonconstricted) increased (p less than 0.005). Subsequently, coincident with development of collateral vessels, RSI ratios increased and RVPRA ratios decreased toward control values. These data suggest that absence of lateralizing RVPRA ratios in the presence of collateral vessels does not mean lack of functional significance of stenotic renal arterial lesions.


Catabolism of secretin by the liver and kidney.

We have investigated the roles of the liver and the kidney in the catabolism of secretin, using a specific and sensitive radioimmunoassay. Dogs were prepared with sampling catheters in the aorta, hepatic vein, portal vein, and renal vein and with electromagnetic flow probes on the portal vein, hepatic artery, and renal artery. Secretin levels in the vessels entering and leaving the liver and kidney were determined by radioimmunoassay and the total mass of secretin [concentration (picograms per milliliter) X plasma flow rate (milliliter per minute)] was calculated during an intravenous infusion of exogenous secretin and during release of endogenous secretin by acidification of the proximal intestine. The total masses of secretin entering and leaving the liver were the same during secretin infusion and during the release of endogenous secretin. Under conditions of elevation of plasma secretin, however, the kidney extracted 30 percent of arterial secretin during secretin infusion and 45 percent during release of endogenous secretin. Clearly the kidney is a major site of secretin catabolism.


Myocardial reperfusion, a cause of ischemic injury during cardiopulmonary bypass.

Reperfusion following myocardial ischemia has been postulated to cause myocardial edema resulting in increasing interstitial pressure and retardation of the microcirculation. If ischemia then is repeated, the additional insult results in increasing edema and possible infarction. In order to test this hypothesis, 15 pigs were placed on cardiopulmonary bypass with coronary perfusion maintained at 100 mm. Hg by a separate pump through the clamped aortic root. Coronary flow and vascular resistance were recorded. Distribution of coronary blood flow was monitored by injection of radioactively labeled microspheres (15 mu). Myocardial extravascular water was measured by simultaneously determining myocardial intravascular water with radioactive iodinated serum albumin (RISA) and total myocardial water with tritiated water (THO). Three 30 minute periods of myocardial ischemia and 5 minutes of coronary perfusion produced (1) a loss of the reactive hyperemic response to ischemia (coronary vascular resistance increased--from 0.295 +/- 0.024, control, to 0.366 +/- 0.042, after anoxia--rather than decreasing with reactive hyperemia induced vasodilatation); (2) a significant maldistribution of coronary flow away from the endocardium (endocardial: epicardial perfusion ratio 1.10 +/- 0.05, control, to 0.69 +/- 0.08, following ischemia, p less than 0.05); and (3) significant myocardial edema. Myocardial extravascular water rose from 46.4 +/- 1.7 ml. per 100 Gm., control, to 52.6 +/- 2.0 ml. per 100 Gm., after ischemia (p less than 0.05), whereas intravascular myocardial volume did not change significantly. Both light and electron microscopic examination of the postischemic myocardium shows interstitial and intracellular edema with typical ischemic changes at a cellular and subcellular level. The significant increase in myocardial extravascular water content associated with this injury supports the concept that myocardial reperfusion plays a role in its development.


Pulmonary resection for localized lesions of cryptococcosis (torulosis): a review of eight cases.

Torulosis is an uncommon, but potentially lethal disease. The aim of this report is to indicate that resection of isolated pulmonary lesions due to torulosis is a safe procedure. Resection has proved useful in the definitive diagnosis and treatment of eight cases seen in this thoracic surgical unit.


Squamous metaplasia of the tracheal epithelium in children.

Thirty-seven (1-6%) tracheas from 2170 children showed squamous metaplasia. (Cases with tracheo-oesophageal fistula and congenital heart disease were excluded). The metaplasia extended into the bronchi in 15 cases. Features of pulmonary retention were present in seven cases. Respiratory infection, probably viral, seemed to be the most significant causative factor in 20 children, including those with cystic fibrosis. Tracheal instrumentation was a possible factor in 11 cases but oxygen therapy alone did not seem important. The metaplasia was almost certainly congenital in one child and probably in two others but no stillborn infants showed metaplasia. In many children the metaplasia seemed to be due to a combination of factors.


Complete correction of transposition of the great arteries with left juxtaposition of the atrial appendages.

Juxtaposition of the atrial appendages is an uncommon anomaly which is usually associated with transposition of the great arteries. Experience with five patients with transposition of the great arteries in combination with juxtaposition of the atrial appendages in whom Mustard's operation was performed is reviewed. Technically, the existence of juxtaposition of the atrial appendages in corrective surgery for transposition does not present any additional surgical problems. Emphasis is placed on the advantages of early complete correction, avoiding the need for palliative procedure.


Selective vagotomy of the canine oesophagus--a model for the treatment of hiatal hernia.

Hiatal herniation caused by contraction of the longitudinal muscle of the oesophagus has been prevented by disconnecting the local vagal nerve supply while preserving the vagal connections to more distant organs. A selective oesophageal vagotomy above the lung hilum may prove an effective adjunct to orthodox hiatal hernia repair in man.


Pulmonary blastoma.

Pulmonary blastoma is now accepted as a distinctive neoplasm. It remains rare, and only 28 cases have been reliably recorded. A further two cases are now reported, and the previous literature is reviewed. There are no specific clinical or radiological features of pulmonary blastoma. The presentation can be that of any other pulmonary tumour although a peripheral situation is usual and a large size is often attained before detection. Pulmonary blastoma is a mixed tumour with malignant epithelial and connective tissue components with a distinctive resemblance to fetal lung. The treatment of choice is surgical excision but the overall prognosis is poor. It is doubtful whether the tumour has a true blastomatous origin.


A unique pulmonary venous abnormality: with associated pulmonary arterial anomaly and arteriovenous malformation.

A man aged 29 was first seen at the age of 11, when he was found to have a congenital anomaly of the pulmonary veins which follow an abnormal course to the hilum. On the left side, two large veins descend peripherally before turning medially towards the left atrium; on the right, several smaller veins follow a similar circuitous route from the periphery, before uniting into two main veins which enter the left atrium. The proximal pulmonary arteries are normal in their pattern of branching and distribution but are dilated and tortous and taper abruptly: the left lower lobe artery is abnormally large almost down to the diaphragm. There is also a systemic arterio/pulmonary venous fistula. There is no haemodynamic disturbance, but gas transfer is slightly impaired, and there is slight arterial desaturation. The congenital anomaly is unique. Reported cases described as having pulmonary venous varices are a heterogeneous group, but one patient described as such shows resemblances to our case.


Ascending aortic false aneurysm following cannulation for perfusion.

A case of false aneurysm originating from the ascending aortic cannulation site in the absence of mediastinal infection is described. Surgical treatment was carried out by means of limited cardiopulmonary bypass and hypothermic circulatory arrest, but the patient died early in the postoperative period. The technical failures responsible for the unsuccessful outcome are emphasized.


Effect of perfusion of bile salts solutions into the oesophagus of hiatal hernia patients and controls.

Tests of the response to perfusion of the oesophagus were made in 54 patients divided into three groups. Group I consisted of patients with symptomatic hiatal hernia, group II hiatal hernia patients with peptic stricture, and group III normal individuals. Each individual oesophagus was perfused at a rate of 45-65 drops per minute over 25 minutes with six solutions: normal saline, N/10 HCl, taurine conjugates of bile salts in normal saline, taurine conjugates of bile salts in N/10 HCl, glycine conjugates of bile salts in normal saline, and taurine and glycine conjugates in a ratio of 1 to 2 in normal saline. It was found that acidified taurine solutions were more irritating than acid alone. With a 2mM/l solution of taurine in acid, symptoms are produced even in controls. With a 1 mM/l solution of the same conjugates, the majority of normal people feel slight heartburn or nothing, and therefore perfusion into the oesophagus of such a solution could be used as a test for oesophagitis.


Oesophageal motor changes in diabetes mellitus.

Radiography and manometry have been used to study oesophageal motor function in a group of 31 diabetics, 23 of whom had alimentary or genitourinary symptoms attributed to autonomic neuropathy. Peristalsis was of diminished amplitude and oesophageal emptying in the 15 degrees Trendelen-Peristalsis was of diminished amplitude and oesophageal emptying in the 15 degrees Trendelenburg position was delayed. The lower oesophageal sphincter pressure was reduced. The changes seldom caused symptoms and they were not confined to those diabetics with alimentary or genitourinary symptoms attributable to autonomic neuropathy. They suggest that autonomic neuropathy in diabetes is widespread and often subclinical. Degeneration of the ganglion cells of the oesophageal myenteric plexus is associated with hypersensitivity of the oesophageal smooth muscle to cholinergic agents. Bethanecol, a cholinergic drug with muscarinic actions, accelerated oesophageal emptying and increased the lower oesophageal sphincter pressure to normal levels in our diabetics but the hypersensitivity to this drug found in the presence of ganglion cell degeneration was not seen. This implies that in diabetic autonomic neuropathy the predominant lesion is in the preganglionic fibres of the vagus rather than in the myenteric plexus of the oesophageal wall.


Observations on oesophageal length.

The subject of oesophageal length is discussed. The great variations in the length of the oesophagus in individual patients is noted, and the practical use of its recognition in oesophageal surgery is stressed. An apprasial of the various methods available for this measurement is made; this includes the use of external chest measurement, endoscopic measurement, and the measurement of the level of the electrical mucosal potential change. Correlative studies of these various methods are made, and these show a very high degree of significance. These studies involved simultaneous measurement of external and internal oesophageal length in 26 patients without a hiatal hernia or gastro-oesophageal length in 26 patients without a hiatal hernia or gastro-oesophageal reflux symptoms, 42 patients with sliding type hiatal hernia, and 17 patients with a peptic stricture in association with hiatal hernia. The method of measuring oesophageal length by the use of the external chest measurement, that is, the distance between the lower incisor teeth and the xiphisternum, measured with the neck fully extended and the patient lying supine, is described in detail, its practical application in oesophageal surgery is illustrated, and its validity tested by internal measurements. The findings of this study demonstrate that the external chest measurement provides a mean of assessing the true static length of the oesophagus, corrected for the size of the individual.


Respiratory disease of workers harvesting grain.

The incidence of respiratory symptoms caused by grain dust during harvesting was surveyed in a group of Lincolnshire farmers. A quarter complained of respiratory distress after working on combine harvesters or near grain driers and elevators, with cough, wheezing, and breathlessness, sometimes so severe as to prevent work. The airborne dust around combine harvesters contained up to 200 million fungus spores/m3 air with Cladosporium predominant while drivers were exposed to up to 20 million spores/m3 air. Verticillium/Paecilomyces type spores, mostly from Verticillium lecanii, Aphanocladium album, and Paecilomyces bacillosporus, were abundant in the dust. Extracts of these species produced immediate weal reactions in skin tests, precipitin reactions with sera, and rapid decreases in FEV1 when inhaled by affected workers. There was no delayed reactions. Results suggest type I immediate hypersensitivity to the spores although the physical effect of a heavy dust deposit could be important. Drivers could be protected by cabs ventilated with filtered air.


Hypoxaemia and cirrhosis of the liver.

In order to determine the frequency of hypoxaemia and to evaluate the role of increased closing capacity in producing hypoxaemia in patients with cirrhosis of the liver, 13 patients with well-established cirrhosis were studied. Arterial blood gases, spirometry, lung volume, and closing capacity measurements were made with the patients in the seated and recumbent positions after exclusion of cardiopulmonary dysfunction. Four of 13 and six of 12 patients exhibited significant hypoxaemia in the seated and recumbent positions respectively. Five of 13 patients showed a closing capacity greater than predicted. This frequency of increased closing capacity was not higher than in a group of smokers of the same age. Unlike Ruff et al. (1971), we did not find a consistent relationship between hypoxaemia and closing capacity.


Quantitation of thick-walled peripheral lung vessels in chronic airways obstruction.

The number of thick-walled peripheral lung vessels (defined as vessels of less than 100 mu diameter with two distinct elastic laminae) was calculated in 50 postmortem lungs. The size of the right ventricle, the amount and type of emphysema, and the proportion of small airways lumen in the lung were also quantitated. Eighteen patients had died as a result of chronic airways obstruction, 17 had symptoms of chronic chest disease but died from some unrelated cause, and 15 had no symptoms related to the respiratory system. The mean number of thick-walled peripheral lung vessels (TWPV) was found to be significantly greater in the fatal disease group than in both of the other groups. No significant difference was found between the mean values of the symptomatic and asymptomatic groups. The mean number of TWPV was significantly greater in cases with a right ventricular weight of more than 80 g than in those with a weight of less than 65 g. Positive correlations were found between the number of TWPV and right ventricular weight, total amount of emphysema in the lung, and the amounts of centrilobular and panlobular emphysema. Significant negative correlations were found between the number of TWPV and both the ratio of the weight of the left ventricle to the right ventricle and the proportion of small airways lumen in the lung.


Cardiovascular depressant effect of protamine sulphate: experimental study and clinical implications.

The mechanisms underlying protamine-induced hypotension and bradycardia were the subject of this investigation. Six groups of dogs with intact circulation were tested in controlled circumstances with various drugs. The following parameters were observed: femoral arterial pressure, central venous pressure, left ventricular pressure and its rate of rise, left ventricular contractile element velocity of shortening, maximal Vce, and cardiac output. The six groups were studied under these pharmacological conditions: ganglionic and adrenal medullary block with hexamethonium chlroide, postganglionic parasympathetic blockade by atropine sulphate, alpha and beta adrenergic receptor block by phenoxybenzamine and propranolol respectively, and depletion of endogenous histamine by compound 48/80 (a condensation product of p-methoxyphenethyl methylamine with formaldehyde). The last group was put on extracorporeal circulation to isolate the vascular tree from the heart. The effect of the drug on this isolated vasculature was observed by recording the femoral arterial pressure. Our findings show that the hypotension and bradycardia are produced by a direct effect of protamine on the myocardium and peripheral vascular system.


Mitral valve reconstruction by posterior cusp advancement using a pericardial graft. Long-term follow-up in nine patients.

Between December 1964 and March 1969, 11 posterior cusp advancement operations were carried out for patients with mitral valve disease in whom there was posterior cusp deficiency. Seven of the nine long-term survivors have required reoperation for recurrent mitral regurgitation, combined in six instances with stenosis of varying severity, the interval between the first and second operations ranging from five months to nine years (average 57-5 months). Histological examination of the pericardial grafts recovered at re-operation has been made and shows that after an initial period during which the graft retains near normal structure, there is a progressive degeneration with fibrous tissue replacement. This process takes place on both surfaces of the graft where there is evidence of vascularization in the zone between the graft remnant and the overlying and increasingly thick fibrous tissue covering. The conclusion drawn from the experience with this small series is that the long-term performance of pericardial grafts designed to restore function to the posterior cusp of the mitral valve is poor and unpredictable.


Mitral valve replacement in the presence of severe pulmonary hypertension.

Thirty patients with severe preoperative pulmonary hypertension (pulmonary artery pressure range 90-165 mmHg, mean 118 mmHg) were reviewed following single mitral valve replacement, with prosthetic valves, within the last 10 years (1964-74). The early and late mortality for this group was no different from that of the total series of mitral valve replacements performed over the same period. Marked postoperative clinical improvement was accompanied by corresponding radiological and electrocardiographic changes. In addition there was a statistically highly significant haemodynamic improvement in the 21 survivors (mean survival time 5 1/2 years). At recatheterization the mean pulmonary artery pressure was 41-5%, the mean wedge pressure 46-3%, and the transpulmonary gradient (PAm-LAm) 36-1% of the preoperative values. It is concluded that gross pulmonary hypertension is not per se a contraindication to mitral valve replacement surgery.


Resection and reconstruction of the sternum: case report.

The case history of a 67-year-old man who underwent a subtotal sternectomy for a tumour of the manubrium and left clavicle is reported. Histological examination revealed a highly undifferentiated metastatic carcinoma: the original tumour was not discovered but the patient was in good condition 10 months after operation. Adequate replacement and stabilization of the chest wall was obtained with autotransplantation of the tibia and muscle flaps.


Paradoxical embolism complicating massive pulmonary embolus.

Paradoxical embolism is an unusual but well recognized complication of venous thromboembolic disease. This case report of a patient with massive pulmonary embolism, who had a paradoxical embolus through a patent foramen ovale, emphasizes that in these circumstances surgical intervention is indicated.


Necrotizing 'sarcoidal' angiitis and granulomatosis of the lung.

A case of necrotizing sarcoid angiitis and granulomatosis (NSG) presenting as a peripheral lung 'tumour' in a 63-year-old man is recorded, and the clinical and pathological features are compared with those of Liebow's original cases. Resection may be avoided if the diagnosis is made by biopsy as the disease is possibly steroid responsive and the prognosis appears favourable. The aetiology is obscure but an immune disturbance is suspected.


Oesophageal moniliasis causing fistula formation and lung abscess.

Oesophageal moniliasis is reviewed and the incidence of fistula formation discussed. A case of oesophageal moniliasis without any predisposing factors, with fistula formation and lung abscess, is presented.