A clinical trial of Amipaque in lumbar myelography.

Three hundred lumbar myelographies using a new water-soluble, non-electrolytic contrast medium, Amipaque, were assessed with reference to: 1) the correlation between radiological and operative diagnosis; 2) the side-effects during and after the myelography. Myelograms of the same reliability as those obtained with other water-soluble contrast media were obtained. However, arachnoiditis as sequelae to previous myelography with oil-soluble and earlier water-soluble contrast media prevented the correct evaluation in some cases. Spinal anaesthesia was not necessary. There was no case of muscle spasms or other serious complication. Eight patients who were re-examined with Amipaque more than two months later revealed no evidence of arachnoiditis as sequelae to the first Amipaque myelography.


Craniopharyngioma: based on 160 cases.

This paper is the outcome of an extensive retrospective study of the clinical and radiological manifestations of a large number of craniopharyngiomas from five leading neuroscience centres in the U.K. The literature about this tumour has been reviewed with particular reference to its origin and radiological manifestations.


Computerized tomography and angiography in subarachnoid haemorrhage.

Our study of 100 multiple aneurysm cases show that 66 survivied the initial danger period either with surgery, or by  conservative treatment. Of these only one may have died subsequently from bleeding from an incidental aneurysm, during a continuing follow-up period now averaging more than seven years. In a separate series of 75 patients presenting clinically with subarachnoid haemorrhage it was possible to lateralize or approximately localize the site of bleeding by CAT in 56; 31 were from aneurysms and 13 from arteriovenous malformations. In the remaining 19 cases CAT was unhelpful in indicating the site of haemorrhage; 12 had aneurysms; no cause was found in the remainder. CAT was more valuable in localization in the seven days following the haemorrhage (86 per cent) than later (34 per cent). The low risk of bleeding from incidental aneurysms makes us feel that treatment confined to the lesion which is responsible for the subarachnoid haemorrhage is not an unreasonable policy in the large majority of these patients. Detailed angiographic study of the site of haemorrhage is performed, but once this has been achieved, more extensive angiography is not routine, but is determined by the requirements of the surgery directed at the site of haemorrhage.


A quantitative assessment of femoral head activity using 99Tcm -polyphosphate and a computer data collection system.

Abnormal femoral head activity in Legg-Calve-Perthes' disease has been measured using 99Tcm -polyphosphate and a gamma camera/computer data collection system. A reference point on the data matrix, which is unaffected by the diease, is used for deriving comparative uptake ratios in each femoral head. The reference point remains unaltered after surgical procedures or short intervals between follow-up studies. Early abnormality can be measured in both unilateral and bilateral femoral head pathology.


A controlled trial of drainage after cholecystectomy.

A prospective controlled trial of drainage after cholecystectomy has been carried out. In a consecutive series of 143 patients undergoing cholecystectomy, 50 patients were randomly allocated to a drainage group and a further 50 patients to a non-drainage group. The remaining 43 patients were drained electively because the common bile duct was explored or because of infection or incomplete haemostasis. There was no significant difference in the incidence of wound infection or other complications between the drainage and the non-drainage groups. The duration of postoperative pyrexia, the number of analgesic injections and the length of postoperative hospital stay were the same in both the randomized groups. One patient in the randomized drainage group had a reactionary haemorrhage from the drain site requiring transfusion. There was no mortality but one patient in the elective drainage group had to be re-explored for a subhepatic abscess. Three patients in this group drained bile from the drain for 3-9 days but all had a T tube in place. This trial fails to demonstrate any advantage or disadvantage in draining the gallbladder bed after cholecystectomy.


Splenogonadal fusion.

The fusion between splenic tissue and the left gonad or the derivatives of the left mesonephros is a rare congenital anomaly first described in detail by Pommer in 1887/9 and divided into two forms by Putschar and Manion in 1956. In the first or continuous type a cord of splenic or fibrous tissue connects the spleen and the gonadalmesonephric structures. In the second type the fused splenomesonephric structures have lost continuity with the main spleen. An example of the continuous form is presented and the previous reports are briefly reviewed.


Primary suture of the perineal wound following rectal excision for adenocarcinoma.

A statistical analysis of the correlations between a number of factors, including age, tumour pathology and surgical management, and the results of primary suture of the perineum after excision of the rectum for adenocarcinoma in 63 males is presented. An unsuccessful outcome was related to the extent of the dissection either necessitated by advanced tumour or resulting from excision of the coccyx. A successful result was associated with small tumours and preoperative antibacterial treatment. Topical antibacterial treatments, topical mercuric perchloride and the drainage route did not appear to affect the outcome.


Effect of plastic skin and wound drapes on the density of bacteria in operation wounds.

Operation wounds were sampled quantitatively by the velvet pad rinse technique to determine the effect of impervious plastic skin and wound drapes on the density of bacteria. A controlled trial (clean operations) revealed no significant difference between the bacterial density of herniotomy wounds for which the skin had been covered with adhesive plastic drapes, and the bacterial density of wounds in which skin drapes had not been used. The bacterial density in the wounds did not differ significantly from that on the adjacent skin; both densities were slightly higher at the end of operation than at the beginning. Within the operation wound, sites of low bacterial density were close to sites with a high density. Staphylococcus epidermidis predominated, while Staphylococcus aureus occurred only once; intestinal species were not isolated. In another controlled trial (potentially contaminated operations) plastic wound drapes gave an equally high reduction in bacterial density before closure of laparotomy wounds after either truncal vagotomy and pyloroplasty or gastric and colorectal operations. The reduction in the density of intestinal species was close to 100 per cent and did not differ significantly from that of alpha-haemolytic streptococci, the density of this species being significantly more reduced than that of staphylococci, diphteroids and bacilli. It is concluded that plastic skin drapes were without influence on the species and density of bacteria in operation wounds. Plastic wound drapes, on the other hand, considerably reduced not only exogenous but in particular endogenous bacteria, which otherwise would have remained in the operation wounds.


Assessment of wound contamination during surgery: a preliminary report comparing vertical laminar flow and conventional theatre systems.

As part of an on-going trial comparing wound infection in "ultra-clean" air and conventional theatres, wound contamination is assessed by a simple wash-out technique. The importance of wound contamination in relation to subsequent wound infection is emphasized. The wash-out technique used is simple to perform and minimizes the risk of contamination. The preliminary results confirm that cleaner air does result in less contaminated wounds.


The treatment of acute abscesses by incision, curettage and primary suture under antibiotic cover.

One hundred and fifty consecutive acute abscesses have been treated by incision, curettage and primary suture under antibiotic cover. The antibiotic used in this series was lincomycin 600 mg i.m. with premedication and clindamycin 150 mg 6-hourly for 4 days postoperatively (children and infants received smaller doses). Similar results for the rate of healing were achieved in all groups of abscesses. A case is made for the use of the technique of incision, currettage and primary suture with antibiotic covere for acute abscesses as an alternative to conventional methods of treatment.


Talampicillin: a new derivative of ampicillin.

Talampicillin is a thiazolide carboxylic ester of ampicillin and is hydrolysed in the intestinal mucosa to release free ampicillin. The mean peak serum concentration of ampicillin occurred one hour after a dose of talampicillin and was about twice that attained by an equivalent dose of ampicillin. The presence of food in the stomach reduced and delayed the peak blood levels but did not affect the total amount of antibiotic absorbed or the urinary recovery. Talampicillin had less effect on the faecal flora in volunteers than ampicillin, and no overgrowth with Candida spp or Staphylococcus aureus was seen. Thirty-eight out of 47 urinary infections were eradicated by a seven-day course of talampicillin.


Immune response to HBsAg and the spectrum of liver lesions in HBsAg-positive patients with chronic renal disease.

Evidence of chronic hepatitis was found on histological examination in nine out of 15 patients positive for hepatitis-B surface antigen (HBsAg) who had either chronic renal failure or a functioning renal transplant. Cirrhosis had already developed in three of the patients, who deteriorated rapidly and died. Liver biopsies from the remaining 12 patients showed the features of chronic aggressive hepatitis in two, chronic persistent hepatitis in four, and minor histological lesions in six. The persistence of HBsAg in patients with renal failure or in those receiving immunosuppressive drugs after a transplant must indicate some impairment of the normal immune response to hepatitis-B viral antigens. Nevertheless, cellular or humoral immunity to HBsAg was detected in all eight patients with chronic hepatitis tested compared with only one out of five with minimal liver lesions, which suggests that the severity of the liver damage may be directly related to the degree of immunocompetence.


Cows' milk protein intolerance: a possible association with gastroenteritis, lactose intolerance, and IgA deficiency.

Twenty-five children with cows' milk protein intolerance were studied. Twenty had presented with an illness clinically indistinguishable from infantile gastroenteritis; an enteropathogenic Escherichia coli was isolated from the stools in two children, and in six another member of the family simultaneously developed acute diarrhoea and vomiting. Twenty-three children had lactose intolerance secondary to cows' milk protein intolerance. Eight out of 20 children were found to be partially IgA deficient. An acute attack of gastroenteritis, in damaging the small mucosa, may act as a triggering mechanism in cows' milk protein intolerance, and a deficiency in IgA may be a predisposing factor in so far as it allows the patient to become sensitised to foreign protein.


HLA-linked genes and islet-cell antibodies in diabetes mellitus.

In a random series of 139 insulin-dependent diabetics aged 30 or under at the onset of disease islet-cell antibody (ICA) was detected in 33 cases (24%). In 27 patients who had had diabetes for less than one year 16 (59%) had ICA. Only one out of 51 patients with maturity onset diabetes who were not dependent on insulin were positive for ICA. Four out of 19 patients with late onset insulin-dependent diabetes had ICA. There was no association between the presence of ICA and any particular HLA phenotype. Within families containing two or more HLA haploidentical siblings with juvenile onset diabetes ICA was a variable finding both in its occurrence and in its relation to the duration of disease. A possible mode of action for the HLA-linked gene may be to permit a rapid immunological destructive process, possibly associated with viral infection.


Assessment of a test of renal viability.

A test of renal viability using the uptake of 125I-iodohippurate by kidney biopsy specimens has been developed. It is applicable to all kidneys irrespective of the method of storage. The uptake of 125I-iodohippurate in experimental kidneys correlated well with warm or cold ischaemia time and subsequent renal function. The test was used for human cadaver kidneys offered for transplantation and there was good correlation between iodohippurate uptake and warm ischaemic time. With this test, prediction of renal function was accurate in 85% of human cadaver kidneys transplanted. Pulsatile perfusion had no effect on cadaver kidneys as measured by this test.


Comparison of prothrombin complex concentrate and vitamin K1 in oral anticoagulant reversal.

A randomised clinical trial was undertaken to compare the value of a factor II, IX, and X concentrate (Prothromplex) with intravenous vitamin K1 (2-5 mg) in reversing an overdose of oral anticoagulants. Rapid partial correction of the prothrombin time, partial thromboplastin time, and the clotting factor assays were observed with the concentrate, but these changes were not always sustained. In contrast vitamin K1 did not show any great effect at two hours but at 24 hours there was always over-correction despite the conservative dosage, prothrombin times being shorter than the therapeutic range. The prothrombin complex concentrate provides a quicker, more controlled but less sustained method of reversing the coumarin defect than vitamin K1. But there remains a significant risk of hepatitis even with a preparation for which strenuous efforts have been made to minimise this risk by screening for hepatitis B virus. The risk should be carefully considered before such concentrates are infused in non-urgent conditions.


Methyldopa and propranolol or practolol in moderate hypertension.

The effect of a low dose of methyldopa combined with (a) a non-selective and (b) a selective beta-adrenoceptor antagonist was studied in a double-blind crossover trial in 24 carefully selected patients with moderate hypertension (mean initial lying blood pressure 189/117 mm Hg). Each patient received methyldopa 750 mg/day, propranolol 240 mg/day, practolol 600 mg/day, methyldopa 750 mg/day combined with propranolol 240 mg/day, methyldopa 750 mg/day combined with practolol 600 mg/day, and placebo for four weeks each according to a random sequence. After four weeks of therapy the most effective treatment, methyldopa combined with propranolol, reduced lying and standing blood pressures by 36-5/21-4 mm Hg and 44-7/25 mm Hg respectively. Thic combination had similar effects to those of the combination of methyldopa with the cardioselective agent practolol except that it reduced lying diastolic pressure further. The combination was more effective than either treatment alone. No significant differences were found between the effects of propranolol, practolol, or methyldopa at the doses used.


Propranolol in hypertension: a dose-response study.

The effect of propranolol was studied in a double-blind crossover trial in 24 carefully selected hypertensive outpatients. Each patient received propranolol 60 mg/day, 120 mg/day, 240 mg/day, and placebo for four weeks each according to a randomised sequence. Propranolol 60 mg/day was no better than placebo in reducing blood pressure. The effects of propranolol 120 mg/day and 240 mg/day were not significantly different. Both doses reduced lying blood pressure by about 20/10 mm Hg from an initial level of 173/104 mm Hg. No difference was detected between the effects of the different doses of propranolol and placebo on weight or on the occurrence of adverse reactions.


Value of the indirect immunofluorescence test in the diagnosis of vaginal candidiasis.

An indirect immunofluorescence test was used to determine the titre of serum antibodies to Candida albicans in 300 female patients. Titres from 1:4 to 1:6 were detected in 85 uninfected subjects and nineteen subjects with gonococcal infection. Titres from 1:4 to 1:16 were also detected in 166 of 169 patients found to be harbouring C. albicans, C. parapsilosis, or C. tropicalis in the digestive tract, genital tract, or both, without overt clinical infection. Titres from 1:32 to 1:128 were detected in one of four patients with vaginal candidiasis as compared with eleven of 23 patients with vaginal candidiasis who were also harbouring C. albicans or C. parapsilosis in the digestive tract. It is emphasized that titres of less than 1:32 did not preclude vaginal candidiasis.


Donovanosis in Papua New Guinea.

Clinical and epidemiological observations on 87 cases of donovanosis seen at Port Moresby General Hospital are presented, with detailed reports of three cases in which the disease was more severe. The circumstances of infection described were consistent with venereal transmission. Chloramphenicol and gentamicin were effective in curing the disease, while streptomycin was found to be ineffective in a number of cases tested. Complement-fixation tests with Donovania antigen revealed the presence of antibodies in all but one of 23 cases tested, and in nine out of fourteen other patients who on clinical grounds were suspected of having donovanosis but were negative by smear test. The complement-fixation test with Klebsiella antigen was found to be highly specific for donovanosis, but less sensitive than the test using Donovania antigen. The intracellular location of Donovania in tissue and the presence of antibodies which are apparently not protective suggest that cell-mediated immunity may be important in defence against Donovania infection.


The locus coeruleus: a cytoarchitectonic, Golgi and immunohistochemical study in the albino rat.

The locus coeruleus of the adult albino rat is a clearly delimited nucleus in Nissl-stained preparations. It is surrounded by an extensive, relatively neuron-free neuropil which is not stained in reduced silver and Luxol fast blue preparations. Most if not all locus coeruleus neurons contain the enzyme dopamine-beta-hydroxylase (DBH) and are thus presumably adrenergic. Two general classes of medium-sized neuron were found in the locus coeruleus in Nissl- and DBH-stained material: multipolar and somewhat smaller fusiform cells. The nucleus was divided into dorsal and ventral parts cytoarchitectonically; the two are distinguished in that (a) fusiform rather than multipolar cells predominate in the dorsal division, (b) cells in the dorsal division are more densely packed, and (c) a majority of the cells in the dorsal division are aligned obliquely in a dorsolateral to ventromedial orientation when viewed in the frontal plane, and longitudinally (anteroposteriorly) when viewed in the horizontal and sagittal planes. The locus coeruleus contains an estimated 1643 +/- 21 neurons (+/- S.E.M.; N=12) as determined in Nissl-stained paraffin sections, and 1439 +/- 29 neurons (+/- S.E.M.; N=6) as determined in DBH-stained frozen sections. The latter estimate is less reliable because of some uncertainty about section thickness. The ventral division of the locus coeruleus has an estimated 210 +/- 11 neurons (+/- S.E.M.; N=6). In Golgi-Cox material counterstained with cresyl violet most locus coeruleus neurons could also be classified as multipolar or fusiform, the latter being somewhat smaller. Typically, both types of neuron have relatively long thin dendrites which branch once or twice and extend well beyond the limits of the nucleus into surrounding neuropil and nuclear areas, particularly the mesencephalic nucleus of the trigeminal nerve and pontine central gray. Spines, consisting of a thin stalk of variable length with a small bulb at the end or just a thin stalk, were scattered infrequently but regularly along all dendrites and a majority of the somata of both classes. Very thin locally ramifying axon-like plexuses were impregnated in several locus coeruleus neurons, as were larger (about 3 mum diameter) projecting axons. Only about 0.07% of the locus coeruleus neurons were impregnated in the Golgi-Cox material although a wide range of impregnation times and ages was used.


Protein binding and subunit association activity in particles reconstituted from Escherichia coli MRE600 50S ribosomal components.

Reconstituted 37S and 48S ribonucleoprotein particles were constructed by incubating Escherichia coli ribosomal RNA with total 50S ribosomal proteins by a sequential incubation method. By comparing the protein compositions of the two types of particles, the proteins that bind to 37S complexes to form 48S particles have been determined. Although only 48S particles could associate with 30S subunits, isolated 37S reconstituted particles could do so if incubated with exogenous 50S proteins. The proteins that bind under these conditions and confer upon particles the ability to associate are L2, L11, L15, L18, and L25. The involvement of these proteins in 5S RNA binding is discussed.


Utilization of dietary nucleic acid purines for nucleotide and nucleic acid synthesis in the mouse.

Three preparations of radioactive yeast nucleic acids were fed to mice. One was labeled predominantly in the guanine moiety, one was labeled predominantly in the adenine moiety, and in one adenine and guanine were labeled equally. Most of the nucleic acid purines produced by digestion were excreted in the urine. However, a small amount was utilized for nucleotide and nucleic acid synthesis in the mouse tissues. Small intestine, liver and skeletal muscle contained most of the purines that were retained in the tissues. Dietary nucleic acid adenine appeared to be utilized somewhat more efficiently than was dietary nucleic acid guanine.


Binding of methylmercuric hydroxide by 4-thiouridine of N-formylmethionyl-tRNA from Escherichia coli.

The binding of methylmercuric hydroxide to N-formylmethionyl-tRNA of Escherichia coli has been studied. In the absence of magnesium ions, methylmercury binds strongly to 4-thiouridine in the eighth position from the 5' end: the dissociation constant is (1.0 +/- 0.2) X 10(-5) M, and the forward and reverse rate constants for binding are (5.3 +/- 0.5) X 10(4) M-1S-1 and 0.38 +/- 0.02S-1, respectively. The presence of Mg2+ prevents this binding, presumably through some conformational change induced in the structure of N-formylmethionyl-tRNA.


Norepinephrine thermogenesis in seasonally acclimatized and cold acclimated red-backed voles in Alaska.

The calorigenic response (millilitres O2 per gram pre hour) to injected norepinephrine (NE) was compared as an index of nonshivering thermogenesis (NST) in the following groups of the Alaska red-backed vole (Clethrionomys rutilus): (1) summer, (2) fall acclimatized, (3) winter acclimatized, (4) 20 degrees C acclimated and (5) 5 degrees C acclimated. The metabolic response was tested at thermoneutrality (25 degrees C) and during cold exposure (5 degrees C). Winter acclimatized voles showed a significantly greater metabolic response to NE than summer voles at both 25 degrees C and 5 degrees C. In summer or winter voles the total metabolic rate after NE (Mne) was similar at 25 degrees C and 5 degrees C but the fraction of the total caused by exogenous NE was lower at 5 degrees C. Thus, thermogenesis during cold exposure and resulting from exogenous NE appear to be based on the same mechanism, and NE has thermoregulatory significance in these voles. The magnitude of the NE response in winter voles was comparable to he highest values reported for bats and exceeded levels reported for other adult small mammal species. Summer acclimatized voles and those acclimatized to 20 degrees C in the laboratory were comparable in their response to NE but winter acclimatized voles were significantly more sensitive to NE than voles acclimated to 5 degrees C. The  seasonal winter peak in MNE coincided with peaks previously found for maximum metabolic capacity (MMAX), maximum brown fat, and the period of coldest temperature in December-January. the ratio of MNE to Mmax was similar throughout the year. The results suggest that small arctic-subarctic rodents have a greater capacity for NE stimulated NST than rodents from temperate latitudes probably because they are acclimatized to colder seasonal condtions.


Study on the efficiency of four procedures for enumerating coliforms in water.

Four coliform estimation procedures were compared as to their ability to enumerate coliform bacteria (oxidase-negative lactose fermenters) from sewage, effluent, and various fresh waters in the lower Great Lakes Region of Canada. Two of the procedures used and which are cited in the American Public Health Association (APHA) Standard Methods were a most probable number (MPN) technique using lauryltryptose broth (LST) and brilliant green bile 2% broth (BGB), and a membrane filtration (MF) technique using m Endo agar LES. The other two procedures were an MPN technique using Parhad chemically defined synthetic medium (PCDS) and BGB developed for Indian fresh waters and an MF (mC agar) technique developed for seawater. Data indicate that within the survey area, maximum population estimates were achieved by the MF procedure using m Endo agar LES and that each procedure was selective for different genera of the Enterobacteriaceae. Discussions concerning standard versus reference procedures are presented.


Phleomycin-stimulated solubilization of deoxyribonucleic acid in Escherichia coli. II. Inhibition of solubilization by bacteriophage T4.

Phleomycin-stimulated solubilization of Escherichia coli DNA is inhibited by infecting the cells with mutants of bacteriophage T4 before treatment with the antibiotic, inhibition requiring phage-specified protein synthesis. Two different modes of inhibition can be differentiated by infecting with mutants which are defective in an early state (gene den A-; endonuclease II-independent inhibition) or a late stage (gene 46-; endonuclease II-dependent inhibition) of phage-directed degradation of host DNA. Endonuclease II-independent inhibition results from interference with phleomycin-induced release of host DNA from the cytoplasmic membrane. In the presence of endonuclease II, the host DNA is converted to fragments, with average molecular weights of 10(6) daltons, the further degradation of which is not promoted by continuous exposure of the cells to phleomycin.


Prodiginine (prodigiosin-like) pigments from Streptomyces and other aerobic Actinomycetes.

About 95 microorganisms, mainly streptomycetes, were examined for prodiginine pigments. The test methods, including some media for stimulating pigment production, are given. All nine strains which produced prodiginine pigments were characterized and the pigments identified. The results were used to propose structures for five prodigiosin-like pigments from actinomycetes reported in the literature between 1947 and 1964. Streptoverticillium sp. 26-1 furnished good yields of butylcycloheptylprodiginine (I), whose antimicrobial activity is given.


Role of lipopolysaccharide in adsorption of coliphage T4D to Escherichia coli B.

Coliphage T4D was strongly adsorbed to intact lipopolysaccharides and alkaline and lipase-treated lipopolysaccharides from cells of Escherichia coli B, but was not so adsorbed to heat-treated cells. In contrast, coliphage T2h was not adsorbed to lipopolysaccharides and the heat-treated cells. Acid hydrolysate of lipopolysaccharides strongly inhibited the adsorption of phage T4D to acetone and ether-treated cells. The adsorption of phage T4D to the acetone and ether-treated cells was markedly inhibited by authentic D-glucosamine, N-acetyl-D-glucosamine, alpha-methyl-N-acetyl-D-glucosaminide, alpha-methyl-D-glucoside, and D-maltose. Authentic D-glucose and E,L-2,6-diaminopimelic acid also showed similar activity. These compounds did not affect the adsorption of phage T2h to the acetone- and ether-treated cells. Concanavalin A and wheat-germ agglutinin inhibited phage T4D adsorption to the acetone and ether-treated cells probably by blocking the phage-receptor sites on the cell wall. The blocking by concanavalin A and by wheat-germ agglutinin was reversed by alpha-methyl-D-glucoside and by alpha-methyl-N-acetyl-D-glucosaminide, respectively. Results suggested the possibility that coliphage T4D requires N-acetyl-D-glucosaminyl-glucose or glucosyl-D-glucosamine residues of the core of lipopolysaccharides for the initial attachment to the cell wall of Escherichia coli B.


[Hemodynamic features of cardiac rejection].

The object of this investigation was to demonstrate the hemodynamic features of cardiac rejection. The postoperative functional evolution of a homogeneous group of unmodified homografts was compared with that of a group of autografts studied by the same protocol. On the 4th postoperative day, a significant decrease was observed initially in the maximum systolic output, the maximum systolic rate index, the mean systolic ejection rate and also in the strength, work and, especially, acceleration of the left ventricles of the homografts. In the terminal phase, the abnormalities already present in these parameters worsened; there was a large decrease in cardiac output, in the stroke volume, in the voltage of the electrocardiogram, and a slowdown in cardiac emptying. During terminal heart failure, the aortic pressure became depressed and the central venous pressure increased rapidly. The hemodynamic reaction following the homoplastic graft was totally different after the 4th day. The comparison of the results obtained from these two experimental groups established that the functional cardiac failure described for the homoplastic transplant represents the hemodynamic expression of acute rejection.


Laryngotracheobronchitis: 2 years' experience with racemic epinephrine.

A relatively new form of treatment of laryngotracheobronchitis, administration of racemic epinephrine by intermittent positive-pressure breathing, was begun in 1973 in the pediatric unit of a large community hospital. A review of 2 years' experience with this treatment, compared with the experience of the 3 years prior to its introduction, has shown that it has reduced significantly the necessity for tracheostomy, to nearly zero, and the duration of hospital stay. A total of 119 children (33.15% of those admitted) received this treatment, the average number of treatments required being 1.8. There were no important complications of treatment and no deaths.


The ultrastructural morphology of gynecologic neoplasms.

Our knowledge of the morphology and pathogenesis of malignant neoplasms of the female genital tract has traditionally depended heavily on their light microscopic characteristics. The introduction of transmission, and most recently, scanning electron microscopy, into the field of gynecologic pathology has resulted in a considerable improvement in the diagnosis of genital cancers that are difficult to classify and has provided valuable information for a better understanding of their subcellular dynamics and pathogenetic development. This paper describes and illustrates the ultrastructural alterations that are considered specific for the most common malignant and potentially malignant neoplasms of the genital system in this context. The value of electron microscopy in the morphologic study of genital cancers warrants its increased use in routine diagnostic pathology, as well as further evaluation of it in basic research in this challenging area of investigation.


Perspectives on research in gynecologic oncology.

Gynecologic cancers present unusual opportunities to explore the fruits of well-designed clinical trials to assess the value of existing treatment using a combined modality approach soon after diagnosis. Cancers of the ovary and uterus have well-defined, familiar natural histories. Pathways of spread are clear and reasons for treatment failure are often blatantly obvious. In the case of ovarian cancer, regional treatment with surgery and radiotherapy has been relatively ineffective and generally has not improved the survival statistics in the last two decades. Spread of tumor cells widely throughout the abdominal cavity outside radiation or surgical fields, even in patients with apparently early disease, is the obvious reason. Studies are underway to assess the impact of long-term postoperative adjuvant chemotherapy with L-phenylalanine mustard, an alkylating agent effective in patients with advanced disease, in early stages of ovarian cancer following surgery and or x-irradiation. The search is on for more effective drugs, or combinations of drugs, that could subsequently serve as more effective adjuvant treatments. In carcinoma of the uterine cervix, chemotherapy as an adjunct to surgery and/or radiotherapy in patients with localized, or locally inoperable disease has been poorly evaluated; little data are available and the value of many established drugs in patients with metastatic cervical cancer is undermined. Some recent evidence suggests the use of hydroxyurea, a drug that by itself is not effective in controlling tumor, may enhance the effect of radiotherapy in patients with Stage II disease. Uterine fundal cancer is often successfully treated by surgery alone. The data for the use of pre- or postoperative radiotherapy are open to considerable question. While the relative nontoxic progesterone compounds are effective in a small but significant fraction of patients with advanced uterine cancer, no properly designed clinical trial has truly evaluated their role as postoperative adjuncts in patients who have resectable tumor but a definite high risk of recurrence. Systemic chemotherapy has been rarely used with any consistency against this tumor but, even so, some chemotherapeutic leads, such as the use of adriamycin, are worthy of exploration. The absence of useful information on systemic treatment of gynecologic malignancies can be traced to the excessive rigid compartmentalization of medical practice. Only recently have investigators of all persuasions begun to explore and exploit some of the therapeutic opportunities, which have been available for some time.


Overview of tumor immunology in gynecologic oncology.

Highlights of recent advances in the field of gynecologic tumor immunology are presented in an effort to demonstrate that at least some cancers of the female genitalia evoke an immune response that can be quantitated in the laboratory. The overview will discuss investigations into the various in vitro assays of both humoral and cell-mediated immunity. The concept of clinical testing of delayed hypersensitivity reactions as it relates to the clinical outcome of the patients with malignancy is presented. Along this line, preliminary studies at our own institution are reviewed in an attempt to establish a rough correlation between patients with a healthy outcome and patients with a strong immunologic index as manifested by skin testing. A progress report on the isolation of tumor-associated antigens in cancer of the cervix and ovary is presented. The prevalence of carcinoembryonic antigen in the plasma of patients with gynecological malignancy is then discussed. Finally, approaches to immunotherapy are discussed, with a suggestion as to future directions.


Purification of soluble human melanoma-associated antigens.

Soluble extracts of melanoma specimens were prepared by 3 M KCl extraction. Delayed cutaneous hypersensitivity reactions to these antigens were noted in 25 of 39 melanoma patients and 7 of 30 patients with other neoplasms. Only 4 of 34 melanoma patients reacted to an extract of autologous muscle. Maximum reactivity to these antigens occurred at 24 hr and was demonstrated histologically by skin biopsy. Chromatography on Sephadex G-150 resulted in two fractions that elicited delayed cutaneous hypersensitivity reactions in melanoma patients. These fractions were subjected to polyacrylamide gel electrophoresis. The first region of the Sephadex 1 gel reacted in 8 of 13 melanoma patients and only 1 of 7 patients with other neoplasms. Some activity was found in other regions of the gel. Skin test activity was confined to the second polyacrylamide gel electrophoresis region of the Sephadex II gel, to which 7 of 9 melanoma patients reacted compared with 1 of 7 patients with other tumors. Recovery of antigenic activity in excess of the total present in the original extract after partial purification indicated that inhibitors of delayed cutaneous hypersensitivity reactions present in the crude KCl extract were removed. A 20-fold increase in antigenic activity per unit protein was achieved.


Precursor lesions for liver cancer in humans.

Our knowledge of the cellular changes that lead to liver cell carcinoma in humans is limited by proper and necessary ethical restriction on clinical research. We know rather more about risk factors, the most important of which is cirrhosis, it seems that both the causative agent and the time of duration of the cirrhotic process are relevent to the magnitude of this risk. According to present knowledge, alpha1-antitrypsin deficiency, alcoholism, naturally occurring carcinogens, drugs, and the hepatitis B virus seem to carry the greatest risk of cancer developing in a cirrhotic patient. Cirrhosis, however, is not an essential prerequisite, and some or possibly all of these agents can also induce cancer without cirrhosis. Bile duct carcinoma commonly follows infestation with liver flukes. Cirrhosis is usually absent but duct epithelial hyperplasia is present prior to the development of cancer. Many cellular changes have been observed in patients and among populations considered to be at risk from liver cancer. Of these, liver cell dysplasia is the most striking and studies of its prevalence, natural history, and association with cirrhosis suggest that it is a precancerous change.


Structural, antigenic, and biological characteristics of precancerous mastopathy.

A biologically significant relationship between precancerous mastopathy (PCM), in situ carcinoma (ISC), and invasive breast carcinoma is evidenced by the following: (a) PCM and ISC are commonly associated with each other and with invasive breast cancer; (b) Stage O PCM and ISC are both associated with an increased risk of subsequent breast cancer; (c) patients with Stage O PCM and ISC are more similar to invasive breast cancer patients than to patients with normotypic breast lesions in regard to family history of breast cancer and parity characteristics; (d) PCM and ISC resemble invasive breast cancers and differ from normotypic mammary epithelium in regard to epithelial cell-lymphoreticuloendothelial relationships; (e) PCM and, particularly, ISC are associated with distinctive immunogenic components; (f) prognostically significant immunogens of invasive breast cancer tissues are related to and antigenically similar to immunogenic components of associated ISC; (g) immunogenic cancers (ISC and invasive) from different patients are antigenically similar to one another; (h) immunogenic cancers (ISC and invasive) from different patients are antigenically similar to some component of murine mammary tumor virus.


The role of the spleen in the repopulation of the haemopoietic system of heavily-irradiated mice.

The respective role of the spleen or of the bone marrow in the regeneration of the haemopoietic progenitor compartment of heavily-irradiated mice has been investigated. Splenectomy was used to this end in animals injected with exogenous isogenic cells or regenerating from endogenous spleen or marrow cells. Analysis of the data as a function of time shows that the presence of the spleen affects marrow CFU repopulation only at the early post-irradiation stages. The expansion of the marrow progenitor pool proceeds, however, rather independently of the spleen and marrow CFU remain eventually as the main source of haemopoietic cells in the surviving mice. Thus the reaction of the spleen may be envisaged as a fast, important but transient contribution to the overall haemopoietic function of heavily-irradiated animals.


A fast and accurate method for calculating Engelberg's synchronization index.

A method is described which makes a fast and accurate calculation of Engelberg's synchronization index possible. The calculation is only based on the growth curve for the synchronous and the corresponding asynchronous population, and makes it unnecessary to calculate the curve for the normalized rate of cell division.


Immunofluorescence studies on gonadotropin releasing hormone (GRH) in the fore-brain and the neurohypophysis of the green frog, Rana esculenta L.

Using antibodies against mammalian LH-RH, the double antibody-immunofluorecence technique has been applied to serial cross sections of the brains of adult Rana esculenta. Immunoreactive material was found in perikarya of an unpaired nucleus in front of the preoptic recess. The axons of these perikarya also contain fluorescing material. They form a single bundle which passes under the preoptic recess, than splits into two tracts, one on either side of the optic chiasm. The two tracts reunite just before entering the median eminence. The axons end near the capillaries in the outer zone of the median eminence. The possibility of two separate  centres for the stimulation of gonadotropic activity in the brains of anurans is discussed.


Demonstration of the tuberoinfundibular tract of the cat: fluorescence histochemistry and electron microscopy.

The distribution of dopaminergic nerve cells in the cat hypothalamus, particularly in the arcuate and periventricular nuclei, and the projections of their axons were studied by fluorescence and electron microscopy after electrothermic coagulation. The majority of these perikarya were located in the arcuate nucleus and the periventricular nucleus dorsocaudal to the optic chiasma. Large lesions caused a wide and diffuse depletion of dopamine fluorescence within the external layer; small lesions caused ipsilateral partial depletion of the dopamine fluorescence. Electron microscopic observations in animals with a lesioned arcuate nucleus revealed that in the external layer degenerating nerve terminals are engulfed by glial processess. In some cases nerve fibers had entirely disappeared and a heavy reactive proliferation of glial processes was observed. Persistence of the form of the median eminence in spite of the extensive degeneration of its nervous elements is considered to depend upon this glial proliferation.


Non-diffusional distribution of radioactivity in the rat median eminence after intraventricular injection of 3H-LH-RH.

The distribution of radioactivity in the rat hypothalamus after intraventricular injection of tritiated luteinizing hormone-releasing hormone (LH-RH) was studied by autoradiography and compared with that expected from Fick's second law which defines the character of ordinary diffusion. The results suggest that LH-RH penetrates through the ependyma and thin subependymal layer in the median eminence and into the suprachiasmatic area by ordinary diffusion. By contrast, concentration of radioactivity in outer layers of the median eminence is increased and, therefore, can not be explained by the diffusion law. In this region incorporation of radioactivity into cell bodies was demonstrated. In the subependymal layer of the median eminence a few rows of silver grains seemingly located in cellular processes were also observed. The diffusion coefficient in the periventricular zone was lower than that in the deeper tissue. It is suggested that the ependymal-subependymal complex of the third and lateral ventricles acts as passive membrane towards LH-RH contained in the cerebrospinal fluid. The significance of this mechanism for the intrahypothalamic transport of RH's is discussed.


Selection of retainers in lower overlay denture-in relation to the abutment tooth mobility--(a laboratory study).

This study was done to evaluate the art of retaining the lower sub/complete, overlay denture, in relation to the abutment tooth mobility while the force was applied to the denture. The lower overlay denture was placed on a simulated model which was constructed of methylmethacrylate and silicone rubber. The author developed and used the special devices for measuring the tooth mobility. Results obtained were as follows: 1. When a force is applied directly to the abutment, the tooth mobility, i.e. the lateral excursion of the tooth, is markedly reduced according to the favorable ratio of the clinical crown to the root length. Splinting by the bar is effective to reduce the lateral excursion. 2. When a force is applied to the denture indirectly to the abutment tooth, the lateral excursion changes greatly according to the retainer selected. 3. The clasp retainer shows the greatest change in the lateral excursion against every loading on the denture. 4. All three types of bar attachment show the least value of lateral excursion.


An analysis of stress distribution in the free-end saddles on the mandibular model.

This experiment was designed to investigate and evaluate the characteristic behavior of mandibular free-end saddle removable partial denture using various retainers. The abutment  tooth displacement and saddle movement were measured while a known vertical force was applied on the saddle. Fifteen different types of free-end saddle dentures were tested, using four various types of prefabricated attachments. Strain-measuring devices were used to measure the extent of abutment tooth displacement and saddle movement. The findings were as follows: 1) The force transmitted to the abutment tooth and the residual ridge were affected by (a) the selection of direct retainers, (b) splinting of abutment teeth, and use of indirect retainers, and (c) the variation in size and shape of the occlusal table on the saddle. 2) The influences by direct retainers a) With use of a resilient joint, the stress was heavily loaded on the residual ridge directly under the direction of force. b) With the joint incorporating the vertical rock-preventing device, a heavy proportion of lateral force was transmitted to the abutment tooth. 3) Both the lateral stress on the abutment tooth and movement of the saddle were reduced more effectively by use of indirect retainers than by splinting of abutment teeth. 4) By reduction of the occlusal area in bucco-lingual dimension, the denture saddle was better stabilized and the lateral stress on the abutment tooth was reduced effectively.


Studies on mechanical properties of denture base material laminated with organic fiber reinforced plastics. Part I. Basic consideration of hybrid construction.

Acrylic resin is widely used as a denture base material, but the upper complete denture fails often during use. Therefore, the denture base made from acrylic resin should be reinforced in some way. Therefore, as a new method of reinforcement on the denture base, the authors devised a method to improve the strength and rigidity by laminating the palatal surface of the denture base with an organic fiber reinforced plastic, the so-called canapé construction. In this paper, as the basic experiment, the flexural strength, fatigue strength and the modulus of elasticity in bending of reinforced acrylic resin by the canapé construction were investigated. As the results, the flexural and fatigue strength are improved respectively 160% and 130% compared to the denture base acrylic resin. And the modulus of elasticity in bending is improved 80%. Therefore, it is considered that this new combination of materials using the canapé construction might be sufficiently applied to the denture base.


The color of gingiva studied by visual color matching. Part II. Kind, location, and personal difference in color of gingiva.

A replica of natural gingival color can be fabricated in a prosthesis. A precise record of gingival color helps to follow-up oral and systemic diseases. A healthy gingival color according to the "Periodontal Workshop Committee I" is 'pink' but no indication is given for color variations by age or position. For more precise definition, therefore, gingival color was examined in the maxillary and mandibular anterior regions by visual color matching using standard color chips after Munsell's system. Gingival color was measured in 60 subjects, in 18 locations around the anterior teeth. 1. The gingival color varies in Hue from 10 RP to 2.5 YR, being mainly between 2.5 R and 5 R; in Value from 4 to 8, maximum between 6 and 7.5; and in Chroma from 1.5 to 7, mainly from 4 to 5. 2. No difference in gingival color is recognized between the male and female, or between left and right sides of the jaw. 3. Gingival color varies with the position of papillary, marginal, and attached gingivae, and the parts corresponding to different teeth have different colors. 4. The gingival color of young persons, differs markedly from that of older people. In all the parts, red Hue is more tinged with purple in the old than in the young; Value is higher in the young; and Chroma is higher in the old.


Continuous determination of beat to beat stroke volume from aortic pressure pulses in the dog.

Present methods for measurement of stroke volume from the aortic pressure pulse are not suitable for beat-to-beat determinations during non-steady state conditions because these methods assume that each systolic ejection is equal to the peripheral runoff during the same beat. We have tested a new method which allows determination of an aortic pressure-volume conversion factor over a wide range of pressures during transient changes in stroke volume and infusions of vasoactive drugs in 6 dogs with chronically implanted aortic electromagnetic flowmeters. Each aortic diastolic pressure decay is approximated by an exponential the time constant of which is used to calculate the pressure loss during systole due to blood flow into the periphery. The total increment in aortic pressure due to systolic ejection, if there were no flow from the aorta during systole, then is calculated. The total systolic increment (delta PSV) is assumed to describe the pressure-volume characteristics during systole and is related to stroke volume by a constant multiplier that is derived from the indicator-dilution measurements of cardiac output. The values for beat-to-beat variations that were determined by use of the aortic electromagnetic flowmeter and by this aortic pressure pulse method were found to be within the range of measurement errors of stroke volume determined from individual aortic electromagnetic flow pulses.


External detection and visualization of myocardial ischemia with 11C-substrates in vitro and in vivo.

To characterize externally detectable changes in myocardial metabolism of free fatty acids (FFA) and glucose associated with ischemia, isovolumically beating rabbit hearts were perfused under conditions of selected flows with cyclotron-produced, short-lived (t1/2 - 20.4 minutes), 11C-labeled isotopes of glucose and FFA. Tension-time index decreased 83% and lactate production increased from 0.5 +/- 1.9 (SE) to 5.3 +/- 2.1 mumol/min per g of dry weight reflecting myocardial ischemia after flow was reduced from 20 to 5 ml/min. After 30 minutes of low flow the myocardial accumulation of 11C-octanoate, expressed as the extraction fraction, declined from 56 +/- 15% to 30 +/- 3%, reflecting metabolic suppression of FFA extraction during low flow. Effects attributable exclusively to prolonged residence time were excluded. Similar results were obtained with 11C-palmitate. The myocardial avidity for 11C-palmitate was demonstrable by rectilinear whole body scanning in dogs given 5 mCi of the agent intravenously. Diminished 11C-palmitate uptake in zones of myocardium rendered ischemic for 20 minutes prior to reflow in intact dogs was delineated by electrocardiographically gated positron-emission transaxial computer reconstruction tomography. Thus, diminished 11C-FFA extraction, externally detectable, accompanies decreased perfusion in isolated perfused hearts, and decreased 11C-FFA uptake reflecting myocardial ischemia in vivo can be evaluated noninvasively by positron-emission transaxial tomography.


Turbulent blood flow in the ascending aorta of humans with normal and diseased aortic valves.

Turbulent blood flow may contribute to a variety of pathophysiological effects. Because of its postulated importance, this study was undertaken to determine whether turbulent flow does in fact occur in the human body. In 15 persons (seven normal, seven aortic valvular disease, one prosthetic aortic valve), point velocity was measured in the ascending aorta with a hot-film anemometer probe. In one normal individual with a high cardiac output, turbulent flow occurred above the aortic valve during peak flow which corresponded to a peak Reynolds number of 10,000. In the other six normal subjects (peak Reynolds numbers of 5,700-8,900), flow was highly disturbed during peak ejection. Each of the subjects with aortic valvular disease and the subject with a prosthetic aortic valve showed turbulent flow during nearly the entire period of ejection, with Fourier components of velocity of significant magnitude up to 320 Hz (the maximum frequency we could evaluate with the equipment available). The turbulence energy density was higher in subjects with abnormal valves (3.2-14.6 ergs/cm3), than in normal subjects (0.6-2.9 ergs/cm3). In subjects with aortic stenosis, turbulence was observed throughout the ascending aorta and in the innominate artery. In others, the turbulence dissipated more proximally. The results of this study indicate that turbulent flow can occur in the ascending aorta of subjects with normal cardiac function; and it occurs consistently in the ascending aorta of individuals with abnormal aortic valves.


The mechanisms of supraventricular tachycardia in children.

The mechanisms of supraventricular tachycardia were investigated in 35 children. Intracardiac electrograms including His bundle potentials were recorded. Atrial pacing and single premature atrial stimuli were performed in the right atrium. Tachycardia was observed and the mechanism elucidated in 33 patients. The atrial activation sequence during tachycardia, including high right atrium, low lateral right atrium, low septal right atrium, and left atrium, together with the ability to initiate or terminate the tachycardia with premature stimuli, were keys to defining the mechanisms. The observed mechanisms included atrioventricular (A-V) node reentry (8), sino atrial node re-entry (5), re-entry through manifest or concealed lateral anomalous pathway (8), re-entry through A-V node bypasses (3), and atrial (7) and junctional (2) ectopic focuses. The frequency of the various mechanisms of SVT is more varied in children than adults, with ectopic mechanisms being more common in children.


Anatomic causes of pulmonary stenosis in complete transposition.

Among 166 specimens with classical complete transposition, pulmonary or subpulmonary stenosis was present in 22 cases. The bases for obstruction were pulmonary valvular stenosis (one case), membranous subpulmonary stenosis (nine cases), anomalous attachment of the mitral valve to the ventricular septum (five cases) and combinations of causes (seven cases). Conditions contributing to combinations of causes included the above, in addition to accessory mitral or pulmonary valvular tissue and herniation of a tricuspid valvular pouch through a related ventricular septal defect. In addition to the 166 cases mentioned, our collection contained six cases of atypical complete transposition characterized by a conus being present in the each ventricel. In three of these six, subpulmonary stenosis was present and caused by a narrow inlet to the left ventricular conus.


Mitral valve prolapse.

For half a century the systolic click and late systolic murmur lay dormant as innocent auscultatory curiosities. The thirteen years since Barlow related these phenomena to mitral leaflet prolapse have witnessed an astonishing information explosion. We have sought to bring together the accumulated data in this review. An Historical Perspective traces the evolution from the now abandoned "pericardial" or "extracardiac" phases, through the leafletchordal phase (redundancy), the myocardial phase (segmental left ventricular contraction abnormalities), to the anular phase (dilatation and faulty systolic contraction). Functional Anatomy is dealt with in terms of pathology, pathophysiology, hemodynamics, angiocardiography, echocardiography, and physical and pharmacological interventions. Clinical Manifestations are concerned with prevalence, natural history, symptoms, physical signs, electrocardiographic abnormalities and roentgen fingings. The four Major Complications- sudden death, infective endocarditis, spontaneous rupture of chordae tendineae, and progressive mitral regurgitation- are examined. Associated Cardiac Diseases, i.e., Marfan's syndrome, ostium secundum atrial septal defect and atherosclerotic coronary artery disease, are discussed, and a section on Treatment deals chiefly with prophylaxis for infective endocarditis and the management of arrhythmias and chest pain. A final section on Evolving Information considers etiologic concepts, the nature of left ventricular contration abnormalities, the cause of chest pain, the relationship to Marfan's syndrome and ostium secundum atrial septal defect, and the effect of aging and sex differences on leaflet chordal redundancy.


Patient acceptance of guanethidine as therapy for mild to moderate hypertension. A comparison with reserpine.

The relative benefits and risks of reserpine and guanethidine were compared in patients with thiazide-treated mild to moderate hypertension (diastolic pressure 95-115 mm Hg). Forty-nine ambulant patients )30 men, 19 women) were treated throughout the study with hydrochlorothiazide, 50 mg/day. In this double blind crossover study each drug was added in graded increments until a predetermined therapeutic response was obtained, blood pressure measurements and side effect scores were evaluated biweekly. Major conclusions of the study were: 1) guanethidine, as well as reserpine, will reduce mild to moderate blood pressures to normal; 2) in most cases, side effects which did occur while taking guanethidine or reserpine were well tolerated and neither drug was clearly superior. Side effects associated with larger doses of guanethidine employed in severe hypertension were absent or only slightly bothersome. Thus, guanethidine apppears to have a good benefit-to-risk ratio in the therapy of mild to moderate hypertension and offers a number of advantages over drugs commonly used in this syndrome. This study refutes the common belief that guanethidine must be reserved only for the treatment of more severe degrees of hypertension.


Functional, chemical, and clinical aspects of proteolytic enzymes in the alimentary canal.

Knowledge of the structure and catalytic function of the pancreatic proteases has increased rapidly in recent years. These advances have been less spectacular in the case of pepsin, and information concerning mucosal enzymes of the small intestine and colon has not even reached the point where one can be certain of their number, far less their nature. The role of these enzymes in disease processes is probably not significant so far as the alimentary tract is concerned, and it is not even certain that the pancreatic proteases influence the course of acute pancreatitis -- they are of more interest to the clinician as diagnostic aids. Since undesirable consequences result from their deficient output, future research should be directed towards improving replacement therapy.


Enzymic analysis of bile acids.

1. The use of enzymes and thin-layer chromatography (TLC) in quantifying individual bile acids from bile or serum is reviewed. 2. Both 3alpha-hydroxysteroid dehydrogenase (commercially available P. testosteroni enzyme) and 7alpha-hydroxysteroid dehydrogenase (E. coli) can be used for spectrophotometric or fluorometric measurement of individual bile acids in TLC eluates and to estimate pool size and half-life of serially labelled samples.


Detection of drugs of abuse by radioimmunoassay: a summary of published data and some new information.

We review the status of radioimmunoassays for detection of abused drugs. Individual assays with use of 125I-labeled antigens are all performed in an identical manner and can be completed in 30 min to 1 h. Combined assays for simultaneous detection of two or more such drugs or assays in which a tritium-labeled antigen is used require 1-2 h for completion. All tests can be performed with 0.1 ml or less of specimen. The assays involving 125I reliably detect urinary concentrations of, per liter, 40-100 mug of morphine, 100 mug of barbiturates, methadone, methaqualone, or benzoylecgonine, and 1000 mug of amphetamine. The assay for morphine involving 3H detects 60 mug/liter. Each assay is capable of providing a qualitative and quantitative estimate of the drugs sought. The 125I-labeled antigens have a usable shelf life of at least two to four months after the antigen is iodinated; the tritium assay is stable for six months. The assays can be performed with use of paper discs that have been suspended in urine and then dried, in place of the liquid specimen. The assays appear to be equally applicable to detection of drugs in urine, blood, saliva, and tissues. All of them are done at ambient temperature and can be used equally well for emergency (stat) tests or mass screening. Except for the benzoylecgonine assay, the clinical reliability of these tests has been demonstrated.


Radioimmunoassay of antibiotics and chemotherapeutic agents.

Theapeutic monitoring of drugs has become of major importance and has stimulated development of new assay systems. Chemotherapeutic agents, many of which are toxic, have until recently been assayed by microbiological systems or other complex techniques that are impractical for a clinical laboratory. Radioimmunoassays have now been developed for some of these agents. We review the techniques for producing hapten protein conjugates and radiolabeling at specific sites on the drug molecule, and the use of these assays in clinical medicine and pharmacology.


Pharmacokinetic interpretation of data gathered during therapeutic drug monitoring.

We review some pharmacokinetic principles that can facilitate interpretation of data obtained during therapeutic drug monitoring: the one- and two-compartment models, volume of drug distribution, drug clearance, organ clearance, bioavailability, first-pass effect, chronic or repetitive dosing, and use of urine and saliva to measure drug clearance and drug binding to plasma proteins, respectively. We also describe use of saliva to estimate rapidly, conveniently, and noninvasively the concentration of the free, pharmacologically active form of the drug as well as the fraction of drug bound to plasma protein.


Differentiation and development of the male.

Male differentiation and development takes place against a tendency towards neutral or feminine differentiation. At each step of development male differentiation results from a suspension of a basic female development and the imposition of male features for which a normal functioning testis is necessary. Once the testis has differentiated early in gestation the establishment and maintenance of normal testicular function will condition male sexual differentiation and maturation. Nature likes to express herself in a rhythmic fashion (circhoral, ultradian, circadian, menstrual, long-term rhythms). To epitomise testicular function throughout development we would propose the term 'ontogenic rhythms' to describe the three periods of maximal testicular activity, fetal, neonatal and adult. This results in the differentiation which eventually determines adult sexual activity.


Fluid and electrolyte metabolism in the newborn infant.

This chapter has sought to gather together the background information on systems controlling homoeostasis of salt and water and their clinical derangement. The temptation to adopt an all-embracing approach to the management of these problems is strong but such an approach is difficult to achieve and indeed dangerous. The circumstances of each sick infant are unique and plans for treatment must be individually tailored and flexible, dependent upon clinical and biochemical progress. Future developments in this field are likely to involve further understanding of renal and hormonal control of fluid and electrolyte and it might be expected that as new methods of management emerge they will be accompanied by their own peculiar risks of inducing secondary homoeostatic disturbances. With regard to infant feeding each advance appears to underline the desirability of breast feeding and support current moves toward provision of low solute feeds for those who are artificially fed. Paediatricians should be vocal in their advocation of breast feeding and ensure that the major principles of salt and water handling are understood by all who work with small infants. An extra scoop of powdered milk can be more of a poison than a food.


Immunosuppression in the treatment of inflammatory bowel disease. II. The effects of azathioprine on lymphoid cell populations in a double blind trial in ulcerative colitis.

Blood lymphocytes and rectal plasma cells have been studied in patients with ulcerative colitis taking part in a double-blind trial of treatment with azathioprine. Treatment for 1 year resulted in a modest fall in blood lymphocyte count, with little change in neutrophils or platelets. There was no major change in the proportions of circulating T and B lymphocytes, suggesting that the number of such cells per millilitre of blood fell in proportion to the change in lymphocyte count. The number of plasma cells in the rectal lamina propria was reduced to a mean less than half that of the control patient group. Blood K-cell cytotoxic activity fell at least 25-fold after 1 year's treatment. PHA-induced cytotoxicity was also reduced, but less consistently. Reduced K-cell activity is interpreted as reflecting depletion of effector cells from the circulation. The fall in lymphocyte count, K-cell activity and gut plasma cells was slow, indicating continuous inhibition of lymphopoiesis or differentiation throughout the trial period. Thus, azathioprine has some immunosuppressive effects which develop only after prolonged treatment. The clinical results of the trial did not show a major beneficial effect of azathioprine in the treatment of ulcerative colitis, nor were there clear correlations between the results of lymphocyte assays and clinical response in individual patients.


Ultrastructure of cells infiltrating human kidney allografts.

Cell infiltration is commonly observed in human renal allograft biopsies. This infiltration was investigated using electron microscopy for a more precise assessment of the nature of these cells. More than 3000 cells infiltrating twenty-five renal allograft biopsies were studied. Six cellular types were distinguished and a mean percentage of each type was calculated. Only one-half of these cells were normal or transformed lymphocytes (including small lymphocytes: 22-3 +/- 3-8%, 'intermediary' cells: 22 +/- 3-6%, blast-like cells similar to MLC transformed lymphocytes: 8-1 +/- 2-4%. A relatively high number of plasmocytes (12-4 +/- 2-5%) and a still higher percentage of macrophages (28-5 +/- 4-6%) were found. Granulocytes represented only 2 +/- 0-8%of the cell population. Variations of the mean percentage of these cellular types were studied in various clinical situations.


Immunological enhancement in the pathogenesis of pyelonephritis.

The role of the immune response in pyelonephritis was investigated by manipulation of the host's immune capacity using the immunosuppressive drugs 6-mercaptopurine, cyclophosphamide and thiamphenicol. Treatment with 6-mercaptopurine depressed the humoral immune response but did not have an adverse effect on the course of renal infection. Thiamphenicol administration prevented the development of pathological lesions but this was due to the anti-bacterial activity of thiamphenicol and not to its immunosuppressive activity. Pyelonephritic animals treated with cyclophosphamide did not produce anti-bacterial antibody. Despite this, cyclophosphamide-treated animals were able to eliminate organisms more readily from the infected kidney than untreated animals with a normal humoral immune response. We believe that blocking of the phenomenon of immunological enhancement explains these unexpected results and that the immune response to renal infection may have an immunoenhancing role protecting the bacterial cell from otherwise effective host defence mechanisms.


The predictive value of specific protein clearances in detecting acute rejection episodes after renal transplantation.

The relative clearances of albumin, transferrin, haptoglobin, IgG, IgA, and IgM and the relative excretion of immunoglobin free lambda- and kappa light chains, lysozyme, and beta2-microglobulin were measured in 24 patients who had recently received renal transplants. Eleven out of 13 acute rejection episodes were predicted 1 to 5 days before the clinical diagnosis was made, and in 2 patients the clinical diagnosis of rejection and the prediction were made simultaneously. Successful antirejection therapy was followed by a decrease in protein excretion; in irreversible rejection episodes protein excretion continued to increase in spite of antirejection therapy. It is recommended that the relative clearances of IgG and haptoglobin be measured daily in patients recently treated by renal transplantation.


Influence of warm and cold ischemia time on initial function and one-year survival of renal allografts.

The influence of the duration of warm and cold ischemia on initial graft function on patient survival, graft survival, and graft function one year after transplantation was assessed in 234 consecutive cadaveric renal transplants. The number of grafts with delayed function was found to increase with increasing duration of the warm and cold ischemia times. On the other hand, the duration of the ischemia times and consequently the initial function, whether immediate or delayed, did not influence the survival of graft and patient nor the function of the graft one year after transplantation.


Renal allograft biopsy: a satisfactory adjunct for predicting renal function after graft rejection.

Forty-four biopsies of transplanted kidneys undergoing rejection were examined by light microscopy without knowledge of the eventual clinical outcome. All patients received extensive antirejection medication. A scoring system based on nine histopathologic criteria was formulated to predict whether the serum creatinine would be less than 1.8 mg/dl (good prognosis), 1.8 to 2.5 mg/dl (fair), or greater than 2.5 mg/dl (poor), two months after biopsy. Predictions were accurate in 37 of the 44 cases. In  some cases with relatively minimal vascular changes the prognosis was poor, whereas heavy cellular infiltreate without vessel damage did not necessarily preclude functional recovery. It was concluded that specific histopathologic pictures should enable the physician to decide whether to institute extensive antirejection therapy or adopt alternative measures.


Management of massive defects in radius and ulna following wringer injury. A case report.

An unusual case of wringer injury in a 29-month-old child demonstrates extensive loss of the diaphysis of both the radius and ulna. Reconstruction consisted of cortico-cancellous autogenous tibial bone grafting of the radius and ulna in two stages. Follow-up of 24 years showed remodeling and good alignment of the entire radius and ulna, culminating in a good functional and cosmetic result. Extensive soft tissue damage and decreased blood supply result in bone necrosis. There is no reason to bone graft the radius and ulna at the same time.


The classic. Streptomycin in tuberculous bone and joint lesions with mixed infection and sinuses.

At the present time, streptomycin represents a tremendous advance in the treatment of patients with these lesions. Streptomycin undoubtedly will be improved upon and superseded by some other agent in the future, giving us better control of this disease and possibly enabling us to eradicate it. In closed lesions streptomycin, in dosages of 90 grams in a period of 90 days, has failed to arrest the tuberculous process permanently. Failure of treatment with streptomycin suggests strongly the presence of a sequestrum, a thick-walled abscess, or inadequate surgery. Healing seems to be related to the duration of administration of streptomycin and not to the total dosage. In patients having sinuses, streptomycin should be continued after healing for a period at least half as long as the healing period itself. Surgical ankylosis, or resection of non-weight-bearing joints, is apparently as necessary now as it ever has been, but is much safer and more effective. Indeed, at times surgical attack is made possible only by the use of streptomycin.


Repair of the spondylolisthetic defect and intertransverse fusion for young patients.

A technique, applicable to young patients with mild to moderate symptoms from a pars defect is described. It is based on the concept that bone grafting of the pseudoarthrosis and an intertransverse fusion using small fesh autogenous concellous grafts from the ilium will prevent further slip. Gratifying results have been obtained in 12 patients, 12 to 18 years of age, with a minimum follow-up of 12 months. The pars defect in all patients healed in 6 months, with a short period of hospitalization and applying a lumbosacral corset as the only means of postoperative immobilization in 7 patients. In 5 patients with a concomitant scoliosis, 3 of whom were surgically treated, the Milwaukee brace was used for immobilization.


Avascular necrosis of the femoral head following cardiac transplantation: report of a case.

Avascular necrosis of the femoral head occurred following cardiac transplantation in a 28-year-old man. After cardiac surgery the patient was treated with prednisone and experienced 2 "rejection" episodes. Hip pain began 5 months postoperatively. Roentgenograms revealed rapidly progressive avascular necrosis in both hips. The sequence of events leading to avascular necrosis of bone in this patient is identical to that following other organ transplantations and includes steroid-induced hyperlipemia, fatty infiltration of the liver, systemic fat emboli to subchondral vessels and avascular necrosis.


The pathology of the joint tissues and its clinical relevance in prosthesis failure.

Thirty-four hip and knee total arthroplasty failures due to infection, loosening, intractable pain and dislocation were examined for synovial and capsular tissue debris. Simiquantitative assessments were made for metal polyethylene, acrylic and cellular debris and inflammation. The most important finding was that in the amounts normally shed into joints, debris particles do not appear to stimulate a polymorphonuclear response. The magnitude of this response correlates best with clinical and/or bacteriological evidence of infection. The quantity of acrylic particles could be correlated with clinical evidence of loosening. Since the correlation between infection and polymorphonuclear leukocytes, debris particles, and the reasons for failure is high, frozen section may aid the surgeon in determining the methods and timing of revision operations.


Renal tubular acidosis: practical guides to diagnosis and treatment.

The syndrome of renal tubular acidosis in some one of its various forms should be suspected when an infant or child has failure to thrive, metabolic acidosis, constipation, diarrhea, vomiting, anorexia, polyuria, or dehydration in infancy. Confirmatory biochemical findings include an inappropriately high urinary pH, inadequate acid excretion and/or abnormal tubular reabsorption of filtered bicarbonate. Growth can be normal when there is sustained correction of the metabolic acidosis through appropriate alkaline therapy.


Atenolol in essential hypertension.

The effect of atenolol, a beta adrenoceptor autogonist, on arterial pressure in patients with benign essential hypertension has been investigated. Eighteen patients were started on atenolol, 75 mg/day; the dose was increased at 2-wk intervals to a maximum of 900 mg if tolerated. When the maximum effective dose was determined, each patient was randomly allocated into a double-blind crossover study comparing atenolol and placebo treatments. The mean supine and erect arterial pressures of the 16 patients completing the run-in period were markedly reduced by atenolol therapy. The pretreatment mean (+/-SEM) supine and erect arterial pressures of the 16 patients completing the run-in period (187 +/-4.7/114 +/-2.6 and 182 +/-4.5/115 +/-3.0 mm Hg, respectively) were reduced (150 +/-5.3/97 +/-2.9 and 151 +/-5.9/100 +/-2.7 mm Hg) with atenolol therapy (p less than 0.01). In the crossover study, the mean (+/-SEM) supine arterial pressure after 8 wk of atenolol therapy in 14 patients (144 +/-5.2/89 +/-1.7 mm Hg) was lower (p less than 0.01) than at the end of placebo therapy (163 +/-4.4/105 +/-2.8 mm Hg). Similar reductions in pressure were recorded in the erect position and after exercise. No severe side effects were observed.


Antiarrhythmic efficacy of N-acetylprocainamide in patients with premature ventricular contractions.

Oral administration of a 1.5-gm dose of N-acetylprocainamide (NAPA) to 9 patients with premature ventricular contractions (PVCs) confirmed previous indirect evidence that this metabolite of procainamide has antiarrhythmic efficacy and potency comparable to those of procainamide. Although the mechanism by which NAPA acts as an antiarrhythmic drug is not known, it was found that the 6 patients with coupled PVCs responded to NAPA therapy and that the 3 patients without coupled PVCs failed to respond. Coupling interval prolongation also occurred during NAPA therapy in 4 of the 6 responding patients. These observations suggest that NAPA may terminate coupled PVCs by slowing and then interrupting conduction of re-entrant impulses, as has been proposed for procainamide. NAPA plasma concentrations of 7.4-17.2 mug/ml were well tolerated by the patients and produced an average fall of 3 mm Hg in mean arterial pressure and a 7.6% mean increase in corrected QT interval.


A sliding intravenous dose schedule for clonidine in hypertensive patients.

Cumulative doses of clonidine were administered intravenously to 8 hypertensive patients to a maximal dose of 100 mug or a blood pressure fall to normal. There was a reduction in mean arterial pressure of 35.6 mm Hg (p less than 0.001), accompanied by a decrease in heart rate of 11.8 bpm (p less than 0.001). There was also a significant linear relationship between the reduction in blood pressure and the intravenous log dose of clonidine with 6.5-fold difference in delta MAP/dose  potency. There was no correlation between the baseline blood pressure and the slopes of dose-blood pressure response curves or the reduction in mean arterial pressure; the rate of the decline of the hypotensive effect of clonidine varied widely between patients and was not related to baseline blood pressure.


Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin.

The aim of the present investigation is to study digitoxin and digoxin protein binding in patients with normal renal and hepatic function, in patients with uremia, and in patients under treatment with hemodialysis for renal failure. The binding of digitoxin and cardioactive metabolites to serum proteins was studied using equilibrium dialysis (an in vitro chemical assay) alone and in combination with a modified 86Rb method. The following values for protein binding were found: DT-3 (digitoxin), 95.7%; DT-2 (digitoxigenin-bis-digitoxoside), 96.5%; DT-1 (digitoxigenin-mono-digitoxoside), 98.7%; DT-0 (digitoxigenin), 92.7%; DG-3 (digoxin), 21.2%; DG-2 (digoxigenin-bis-digitoxoside), 16.3%; DG-1 (digoxigenin-mono-digitoxoside), 18.5%; and DG-0 (digoxigenin), 13.3%. In vitro addition of procainamide, phenytoin, heparin, and rifampicillin did not influence the in vitro binding of digitoxin. Protein binding of digitoxin showed small individual variations in patients with normal renal and hepatic function. Uremia per se did not influence the in vitro binding of digitoxin. There were marked changes in digitoxin and digoxin protein binding during an 8-hr hemodialysis, digitoxin binding decreasing from 97.1% to 93.7% (p less than 0.0025) and digoxin binding from 23.5% to 15.4% (p less than 0.05). In the uremic patient the metabolic pattern of digitoxin tended toward a decrease in protein-bound metabolites.


Clinical testing of the radiosensitiser Ro-07-0582. I. Dose tolerance, serum and tumour concentrations.

Patients have been given single oral doses of the radiosensitiser Ro-07-0582 and serum concentrations have been attained in the range expected to be of value in radiosensitisation. Immediate gastrointestinal side effects appear to limit the dose to below 140 mg/kg but radiosensitising serum levels of approximately 200 mug/ml can be attained. Tolerance may be improved by giving anti-emetics and a more palatable preparation. Estimates of the concentration of Ro-07-0582 in tumour have ranged from 12 to 92% of the serum concentration at the time of determination.


Clinical testing of the radiosensitiser Ro-07-0582. III. Response of tumours.

The nitro-imidazole Ro-07-0582, a known radiosensitiser of hypoxic cells in animals, was administered orally to seven patients with metastatic tumour, before irradiation. The delay imposed on the growth of tumour treated in this way was compared to that of tumour in the same patient treated with radiation alone. Two patients died before any assessment of response could be made. Qualitative evidence from a further three patients suggested some enhancement of radiation effect in two patients but not in the third. Quantitative evidence was obtained from the remaining two patients. In one, a patient with multiple pulmonary metastases from a carcinoma of the breast, no enhancement was shown. In the other, a patient in whom 21 subcutaneous metastases from a carcinoms of the cervix of the uterus were measured, an enhancement ratio of 1-2 was found. This agrees with the value from the same patient's skin when rendered artificially hypoxic, as reported previously. The conditions under which quantitative information may best be obtained in this type of trial are described and various factors affecting the interpretation of results are discussed. Ro-07-0582 has thus been shown to have a radiosensitising effect in man and may therefore prove of value in radiotherapy.


Branched-chain amino acids, nitrogen excretion and injury in man.

1. Venous blood concentrations of the branched-chain amino acids, valine, leucine and isoleucine, and urinary nitrogen excretion have been measured in sixteen adult males, from 2 h to 7 days after injury, and in four adults after elective skin grafts. 2. In the injured group the concentrations of these amino acids rose significantly 24 h after injury and had doubled at 4 days and remained high; in contrast the skin-graft patients showed no significant change. 3. In those injured patients with initial hyperketonaemia, defined as more than 0-2 mmo1/1, the increase in concentrations of branched-chain amino acids at the fourth and seventh days after injury was significantly less than in those with normoketonaemia, and was accompanied by lower urinary nitrogen excretion throughout the whole period. 4. It is suggested that the changes in the concentration of branched-chain amino acids after injury indicate decreased uptake by muscle or excessive release due to an imbalance between protein synthesis and protein catabolism in this tissue.


[Roads in the phantasms of psychotic children].

The authors have previously analyzed themes such as 'the rails', 'the sun', 'the house' in the drawings and modellings of very regressed, psychotic children. Here we have 'the roads', another anxiogenous subject. The mental condition of the young patients expresses itself clearly in the way the theme is treated in plastic works, and even in the stage play. The colours used, the entanglement, the importance of cross-roads, and the delirious comments are studied. The image of the roads is changing with progressing success of treatment.


The value of the study of the psychopathology of expression.

The study of the psychopathology of expression deals with abnormal tendencies and themes in paintings and creative products of mental and other patients, and the same kinds of themes in the work of normal artists. Its values are as follows: for diagnosis in revealing patients' problems through observation of deviations from normal tendencies and themes in their art; for treatment in giving insight and understanding to the patient; in relation to modern art because it makes clear what is often confused and bizarre; in relation to classical art because some of the same themes and tendencies are often present and it helps us to understand them; in relation to the study of creativity because sources of inspiration become apparent when underlying themes and tendencies are revealed. It cannot, however, explain fully the real nature of art.


[Drawings of young drug addicts].

Due to addiction being a complex process of illness, there are no available designatory aspects facilitating the pictorial illustration of addiction. To appreciate pictures of young drug addicts, therefore, it is necessary to know in which stadium of the addiction process (intoxication or treatment stadium, or detachment phase) the pictures were taken; when the addiction began (prior to, in the course of, or after completion of puberty), and how long the addiction is pertinent. Pictorial depictions of a 22- and a 17-year-old man, as also of a 15-year-old girl, who are polytoxicomane, and who were in the detachment phase, are demonstrated. The common quality of these pictures is to be noted in the earnestness with which these young people endeavour to recognise the problems of their lives (e.g., the threat to their inner existence); the confrontation of the so-called problemless world versus the problematic drugs world, and to express this pictorially.


Radiographic findings in aneurysms of the aorta.

The use of specific radiographic criteria in the investigation of an aneurysm of the aorta will enable the physician to determine its etiology with a high degree of accuracy. The etiology, location, type, and extent of an aneurysm determine the proper mode of therapy. Aortography, therefore, is the single most important examination for the diagnosis, and will predict the ultimate prognosis in a patient with an aortic aneurysm. This review critically evaluates major recent articles on aortic aneurysms, emphasizing radiographic findings which have a high degree of reliability and cautioning the reader about nonspecific signs which have been reported. Each type of aortic aneurysm is described in detail, stressing criteria which allow the radiologist to be as specific as possible in determining the etiology and extent of the aneurysm.


A double-blind study of flupenthixol ('Fluanxol') in general practice.

A double-blind crossover trial was carried out in the general practice to compare the effectiveness of flupenthixol and placebo in 43 patients with mild to moderate anxiety/depression states. Patients received either 0.5 mg flupenthixol or identical placebo tablets 2 to 4-times daily for 2 weeks and were then crossed over to the alternative preparation for a further 2 weeks. A simple 5-point rating scale was used to assess patients' symptoms at first visit and at subsequent follow-up. Even though there was a high placebo response, the results showed flupenthixol to be significantly more effective than placebo in relieving symptoms. Few side-effects were reported and were mild in nature.


The use of a biological preparation in the treatment of some gynaecological diseases.

A double-blind between-patient trial was carried out in 200 women suffering from dysfunctional menorrhagia (142) or from menorrhagia associated with uterine fibromyomatosis (58) to assess and compare the effectiveness of a polypeptide preparation ('Lysometra') and methylandrostendiol in reducing hyperoestrogenism and clinical symptoms. Three 20-day courses of intramuscular injections of either 2.5 ml 'Lysometra' or 5 mg methylandrostendiol were given to matched pairs of patients, with an 8-day interval between. Results, as assessed by absolute and percentage changes in total urine oestrogen levels and by overall clinical response of patients, showed that 'Lysometra' produced a statistically significant greater effect than methylandrostendiol. The biological preparation was well tolerated and no unwanted side-effects were reported.


Evaluation of tolmetin in the treatment of arthritis: open and controlled double-blind studies.

In a 6-week open study in 24 patients with rheumatoid arthritis, tolmetin was shown to have analgesic and anti-inflammatory activity at daily doses in excess of 1200 mg per day and produced statistically significant reductions in overall joint pain, walking time and articular index. The drug was well tolerated, but 2 patients were withdrawn because of persistent indigestion and 1 because of an urticarial type rash. In a double-blind crossover comparison against indomethacin and placebo in 22 patients, 1400 mg tolmetin daily showed efficacy comparable with that of 150 mg indomethacin daily. Few side-effects were reported and did not necessitate any patients being withdrawn.


Clinical experience with indanyl carbenicillin in urinary tract infections.

A trial was carried out in 30 patients to assess the effectiveness of indanyl carbenicillin in acute or chronic urinary tract infections, many of which were complicated by a pathological urological or medical condition. In all patients, infection was due to a single species of pathogen: E. coli (19), Proteus (6), and Pseudomonas (5). Oral doses of 1 g indanyl carbenicillin were given 6-hourly for an average of 10 days. Results showed a clinical and bacteriological cure in 13 (43.8%) patients. In 6 patients, although there was initial clinical improvement, the pathogen developed resistance during therapy. In 7 patients, there was super-infection with another organism. Four patients were withdrawn early in treatment because of side-effects, mainly gastrointestinal in origin. Indanyl carbenicillin proved very effective in eradicating all strains of Proteus and Pseudomonas and 12 (70.6%) of the 17 strains of E. coli in patients completing the full course of treatment.


Severe viral pneumonia in young adults.

Three patients with primary group-A influenzal pneumonia had diffuse pulmonary infiltrates, arterial oxygen tensions (PaO2) less than 50 mm Hg while breathing oxygen at 1 atm (fractional concentration of oxygen in the inspired gas (FIo2) equals 1.0), and right-to-left pulmonary shunts greater than 45 percent of total pulmonary blood flow. At an FIo2 of 1.0, end-expiratory pressure (EEP) was added in increments of 2 to 5 cm H2O every 30 to 60 minutes until the PaO2 was above 200 mm Hg and right-to-left shunting had fallen to less than 25 percent. The FIo2 was then lowered to 0.5. Using this systematic approach, all three patients required an FIo2 of 1.0 for less than 12 hours, minimizing the risk of oxygen toxicity. Two of the three patients did not require mechanical ventilation and breathed spontaneously while on continuous positive airway pressure (CPAP), and one of them tolerated an EEP of 31 cm H2O. Two patients survived, and one died of a neurologic complication of cardiopulmonary arrest, despite clearing on the chest x-ray film and improved gas exchange. Therapy with CPAP can be safely used in adults and has practical as well as theoretic benefits over continuous positive-pressure ventilation.


Measurement of right and left ventricular ejection fractions by radionuclide angiocardiography in coronary artery disease.

Utilizing a dynamic radionuclide method, the right and left ventricular ejection fractions were measured in 96 men with arteriographically defined coronary arterial disease and in 14 normal subjects. The radionuclidically estimated right ventricular ejection fraction (RVEF) correlated with the RVEF measured with biplane cineventriculographic studies (r = 0.80; n = 43), and the left ventricular ejection fraction (LVEF) measured from radionuclide data have been shown to correlate with the LVEF from single-plane cineventriculographic studies (r = 0.89; n = 60). The mean normal RVEF was 0.57 +/- 0.01 (SE) (range, 0.51 to 0.64), and the mean normal LVEF was 0.66 +/- 0.01 (range, 0.57 to 0.74). The LVEF was decreased in the men with coronary arterial disease and isolated obstruction of the left anterior descending coronary artery, double-vessel disease, and triple-vessel disease, but was normal in those with isolated right coronary disease. The RVEF was normal in each of these groups, except those with triple-vessel disease. Myocardial infarction was associated with impairment of LVEF, although some patients without myocardial infarction had depressed LVEF. The RVEF was preserved in patients with infarction, except those with multiple myocardial infarctions. Thus, impaired LVEF in coronary arterial disease is associated with myocardial infarction, and RVEF is relatively preserved except in multiple-vessel disease and myocardial infarction and in association with impaired LVEF.


Comparison of the acceleration and velocity of shortening of the ventricular radius. Their potential applicability of noninvasive measurements of ventricular performance.

The maximal rate and maximal acceleration of shortening of the radius of the minor axis of the ventricle were correlated with various indices of ventricular performance in 20 patients with angina. The maximal acceleration of shortening showed a closer correlation with the ejection fraction, rate of change of flow, and ejection rate of change of power than did the maximal rate of shortening. It also distinguished more sharply between patients with normal and abnormal values of these indices, showing no overlap of values. The maximal rate of shortening showed a less distinct separation. These observations suggest that the acceleration of shortening of the ventricular radius reflects ventricular performance more closely than does the rate of shortening of the radius. These results are relevant in regard to potential applications of these indices by noninvasive techniques, particularly echocardiography.


Mycotic aneurysm of the thoracic aorta caused by Aspergillus fumigatus.

A 54-year-old diabetic patient had unexplained fever and embolic occlusion of the splenic, right renal, right hypogastric, right superficial femoral, and left popliteal arteries. Aspergillus fumigatus was recovered from a femoral clot. An aortogram revealed a mycotic aneurysm of the thoracic aorta to be the source of the infected emboli. Surgical excision of the aneurysm and therapy with amphotericin B were unsuccessful.


The management of chronic hysteria: a review and double-blind trial of electrosleep and other relaxation methods.

The effectiveness and mode of action of electrosleep therapy in chronic hysteria was evaluated in a double blind trial with a 1 month follow-up. Matched groups of hysterics were treated with central electrical stimulation and relaxation, peripheral electrical stimulation and relaxation, or relaxation only. Autogenic training exercises were used initially to standarize the relaxation instructions for all the patients. Central electrical stimulation has no specific benefit for hysteria. Rhythmic peripheral stimulation does increase the effect of verbal suggestions to relax initially but has no long term advantage over relaxation alone. Regular brief periods of relaxation can improve the mood and diminish the anxiety level of psychiatric outpatients with hysteria but have no persistant benefit for sleep disturbance or hypochondriasis. The best treatment of depression in chronic hysterics was found at follow-up to be relaxation without electrostimulation. Specialized somatic and psychotherapeutic methods have no advantage over treatment with low doses of anxiolytic drugs, reassurance, suggestion, and regular periods of relaxation.


[Antibody response to group A streptococcal exoenzymes (author's transl)].

Sera from normal controls from patients with streptococcal diseases, and from other patients whose serum was sent for anti-streptolysin 0 determinations were tested for antistreptolysin 0 (ASO) and anti-DNase B (ADB) antibodies. The Streptozyme test was performed on the same sera. The upper limits of normal in the control population were established as 160 units for ASO and as 240 units for ADB, respectively. The usefulness of the ADB test in addition to the ASO test was confirmed: when both tests were performed elevated titers could be demonstrated in a higher percentage of various streptococcal diseases. With respect to streptococcal infections of the skin the anti-DNase B-test was superior to the ASO test. In this study of the Streptozyme test showed an elevated antibody titer in a lower proportion than the other two tests.


Clinical use of topical cortisteroids.

The action of topical corticosteroids is anti-inflammatory and antimitotic. By the use of laboratory and clinical trials they can be divided into four grades of potency. Weak steroids may be made more potent by better penetration which can be achieved by plastic occlusion or by alteration of the vehicle in which they are suspended. Local side-effects of topical corticosteroids are described and attention is drawn to the face as a particularly vulnerable area. Use of large amounts of the most potent steroids has produced Cushingoid states normally associated only with systemic steroids, and this is more likely if the patient has liver damage. Practical advice on the choice of steroid for particular disorders is given and the importance of intermittent treatment both for safety and effectiveness is stressed.