Activity of antibiotics in contaminated wounds containing clay soil.

Most traumatic wounds are contaminated to some degree by soil and run a high risk of infection. The presence of soil in wounds interferes with natural tissue defenses, which include phagocytosis and serum bactericidal capacity. The experimental studies reported herein clearly demonstrate that soil also limits the antibacterial effects of specific antibiotics. This inactivation appears to be the result of a chemical reaction between the charged antibiotics and the soil particles.


Factors influencing mortality and morbidity from injuries to tha abdominal aorta and inferior vena cava.

Fifty patients having undergone operation for injury to the abdominal aorta and/or vena cava at the University of Alabama Hospital are reviewed. Factors influencing mortality include mechanism and location of injury, presence of shock, associated vascular and visceral organ injuries, and delay in treatment. Rapid restoration of blood volume and control of hemorrhage are the primary goals of resuscitative measures. Only with a preconceived and coordinated plan can the surgeon fully employ the necessary skills in the management of these serious injuries.


Prophylactic interruption of the inferior vena cava. A retrospective evaluation.

One hundred sixty patients were retrospectively evaluated to determine the effect of prophylactic inferior vena caval interruption in association with aortic surgery. Sixty-three patients underwent aortic procedures without inferior vena caval interruption and ninety-seven patients underwent placement of an Adams-DeWeese clip as prophylaxis against pulmonary embolism. Pulmonary embolism occurred in 10 per cent of the group without the clip and in no patients in the group with the clip. The incidence of deep vein thrombosis was identical in both groups (10 per cent). The 6 per cent rate of early (within 6 months) postoperative leg edema in the group with the inferior vena caval clip was a significant problem in only one patient after twenty-four months. Prophylactic interruption of the inferior vena cava has been shown to be a safe method of decreasing the incidence of pulmonary embolism without increasing the incidence of venous-related complications.


Hemangiopericytoma. Literature review and clinical presentations.

Hemangiopericytomas are soft tissue sarcomas of vascular origin, comprised of pericytes. They have been reported in the extremities, head and neck, back, retroperitoneum, and abdomen. The criteria for the diagnosis and treatment are reviewed. Wide local ablation of the tumor is necessary to prevent local recurrence. Fifty per cent are malignant, although regional node spread is infrequent. Ultrastructural studies are necessary to differentiate hemangiopericytomas from other sarcomas. Long-term follow-up of all cases is essential for optimal clinical management.


Scribner shunt conversion to arteriovenous fistula.

Scribner shunts were converted to arteriovenous fistulas in twenty-six patients, with long-term success in twenty patients. Infection with loss of the fistula was a problem in two patients. The fistulas were used for home as well as center dialysis and as a primary blood access site as well as a backup site.


A new instrument for inserting a U tube.

A new instrument for the placement of U tubes through malignant and benign biliary strictures consists of a 3 mm Bakes dilator modified by a circumferential groove and a small hole through its tip.


[Gas chromatographic determination of the solubility coefficient for volatile anaesthetics (author's transl)].

For the determination of the solubility coefficient of volatile anaesthetics in Schindler's liquid culture, modified by Karzel, a gas-chromatographic analysis with direct-injection-method was used. A well defined volume with a known concentration of the anaesthetic was added to a vessel with known volume. After equilibration the concentration of the inhalational anaesthetics was determined in the liquid at various temperatures. The solubility coefficient and the temperature coefficient were then calculated from these data. We obtained the following solubility coefficients at -4 degrees C (37 degrees): for halothane 1,07 (0,77), for enflurane 1,14 (0,70), for methoxyflurane 4,92 (3,23) and for isoflurane 1,13 (0,82). In Schindler's liquid culture modified by Karzel the values at 24 degrees (37 degrees) were: for halothane 1,33 (0,92), for enflurane 1,32 (0,87), for methoxyflurane 6,61 (4,48) and for isoflurane 1,19 (0,98). The temperature coefficient for this temperature range were in water (in Schindler's liquid culture) for halothane: -2,31 . 10(-2) K(-1) (-3,15 . 10(-2) K(-1)), for methoxyflurane: -13,0 . 10(-2) K(-1) (-16,48 . 10(-2) K(-1)), for enflurane: -3,38 . 10(-2) K(-1) (-3,46 . 10(-2) K(-1)) and for isoflurane: -2,38 . 10(-2) K(-1) (-1,62 . 10(-2) K(-1)).


[A new method for the continuous determination of ethrane in the blood and the expired air by means of gaschromatography as end-analytic system (author's transl)].

A method for continuous measurement of the anaesthetic Ethrane in blood and gas samples is described. Using the same GC-parameters for the analyses of gases and blood extracts, a short GC-column together with high oven temperature as well as shortening of preparation (extraction) time allows the analysis of two blood samples and one gas sample within 15 minutes' steps (the time for an additional gas sample analysis being max. 3 min). Thus a quasi simultaneous follow up of the course of anaesthesia in animals and in humans may be guaranteed.


[Enflurane anaesthesia and plasma cortisol (author's transl)].

The influence of enflurane on adrenocortical function was investigated by determining the concentration of plasma cortisol by a radioimmunoassay during general anaesthesia and abdominal operations. Thirty minutes after the start of anaesthesia with enflurane 0.8--2.0%, N2O:O2 (2:1) and pancuronium, the plasma cortisol decreased slightly in the preoperative period; it increased markedly and continuously during the intra- and postoperative period. There was no correlation between plasma concentrations of enflurane, determined by gas chromatography, and cortisol.


[TTC-reducing activity of alveolar macrophages under the influence of halothane and nitrous oxide (author's transl)].

In order to study the influence of two inhalational anaesthetics on metabolic activity of macrophages, we exposed alveolar macrophages (AM) from guinea pigs to both nitrous oxide (N2O) and halothane-N2O in vitro. We examined the enzymatic activity, which is bound to an intact metabolic phase, by application of the triphenyltetrazolium-chloride test (TTC-test). The content of the enzymatically to formazan reduced TTC was measured spectro-photometrically. Incubation of AM for 60 min in 1 to 4 percent halothane vaporized in air produced only a minimal, statistically insignificant depression of TTC reduction activity (TTC-RA). Halothane plus N2O-O2 (80:20) caused a statistically significant depression of TTC-RA. The reponse is graded in relation to the halothane dose. Exposure to monoanaesthesia with N2O also resulted in reduction of metabolic activity. These data demonstrate that inhalational anaesthetics inhibit the capability of AM to reduce TTC.


[Investigations about the influence of halothane and enflurane on the nuclear metabolism of bronchial mucosa cells of the dog (author's transl)].

The influence of halothane and enflurane on the nuclear metabolism of bronchial mucosa cells was investigated over ten hours on 5 dogs each anaesthetized with halothane or enflurane. Desoxyribonucleinic acid (DNS) and, for the arginine and lysine-rich histone fraction the basic amino-acids arginine and lysine were measured. During the ten hours of anesthesia there was a decrease of all patterns, reversible in a control 48 hours after the end of anesthesia. The decrease of DNS and arginine was similar to each other, but that of lysine was delayed. The results indicate a reversible retardation of the nuclear metabolism. The site of action is probably in the activated zone of nucleus.


[On the problem of optimal warming and moistening of the inspired gases in controlled and assisted artificial ventilation (author's transl)].

The physiological significance of adequate temperature and humidity of respiratory gases and the problems of technical realization are demonstrated. Humidifying and warming of gases by the principle of bubbling through a heated waterbath are believed to be best. The problems with these techniques e.g. dependence of temperature and relative humidity of the gases delivered to the patient on respiratory minute volume, material of the tubing and room temperature are shown. A simple solution to these problems without the need of electrical heated tubing is offered. A new electronically controlled humidifier (H.R.P.-Humidifier 2000) with special developed tubing is presented. Optimal temperature and relative humidity of the respiratory gases is guaranteed by the high efficiency humidifier, and additional measurement and regulation of temperature close to the patients tracheal tube. The problem of increased amounts of condensed water in the tubing is solved by the H.R.P. special tracheal tube adapter with an automatic water exhaust. In addition the hygienic problems of artificial respiration can be solved optimally in combination with the complete H.R.P.-System 2000.


[The influence of some inhalation anaesthetics on the intracranial pressure with special reference to nitrous oxide (author's transl)].

The influence of inhalation anaesthetics on intracranial pressure (ICP), arterial blood pressure and cerebral perfusion pressure (CPP) was investigated on 12 unconscious patients with head injury having an initial ICP of about 20 mm Hg. Halothane, enflurane and nitrous oxide induced a considerable rise of ICP during a 15 to 25 minute period of observation. The moderate fall in blood pressure caused by halothane and enflurane enhanced the reduction of the calculated CPP. Besides, a regular fall in blood pressure of about 16% was observed under the influence of nitrous oxide, subsequently reducing the CPP in some cases under 40 mm Hg. Inhalation anaesthetics, including nitrous oxide, should therefore not be used in patients with decreased intracranial compliance before the increased ICP is treated.


[Methods influencing intraoperative heat balance in the sterile enclosure (author's transl)].

More and more operations are performed in a sterile enclosure ("Sterilboxe") with a high fresh air turnover to achieve an optimum aseptic standard. This study investigated the question whether the climate of the "Sterilboxe" has a depressing effect on the body temperature of anaesthetized patients. Furthermore various devices were tested for their value in compensating for heat losses. The temperature of 55 patients was recorded during major operations. We found evidence, that there was regularly a fall of core temperature during operations in the "Sterilboxe", somewhat different to the behaviour of temperature in conventional theatres. Three methods for the compensation of heat loss were compared each against other and against the control whilst continually recording the oesophageal temperature. In the control group the temperature fall was 0.44 degrees C/h, in the group in which respiratory gases were optimally warmed and humidified the decrease was only 0.11 degrees C/h. Warming up all perfused liquids in a water-bath heat-exchanger showed a fall of temperature of 0.2 degrees C/h; with a Fenwal heatexchanger temperature decreased by 0.27 degrees C/h.


[R 33812 (domperidon) i.v. and orally as antiemetic adjuvans for short anaesthetics induced with etomidate. A comparative study (author's transl)].

R 33812 is being studied as an antiemetic adjuvant to anaesthesia for minor gynecological surgery. 150 patients received 10 mg Diazepam orally as a premedication and of these 3 groups of 50 received R 33812 in doses of 4 mg or 8 mg i.v. before anaesthesia or 10 mg orally together with premedication. Between series I and II a dose-related trend p = 0,065 was observed. No side effects were reported. The pharmacological interdependence of this combination is discussed as well as the consequences for general practice especially for the improved form of oral medication with R 33812.


[Isobaric spinal anaesthesia with bupivacaine and tetracaine (author's transl)].

4 ml 0.5% solutions of bupivacaine and tetracaine without the addition of a vasoconstrictor, approximately isobaric, were used for spinal anaesthesia on patients in the sitting position. The sensory and motor block due to the two local anesthetics was tested and compared. The mean time on onset of complete analgesia was the same for both local anaesthetics (9 and 11 min), as was also the highest level of analgesia (T10). The duration of maximal extension of analgesia was on an average 45 min longer due to tetracaine (bupivacaine 105 min, tetracaine 150 min). The duration of maximal spread of the blocked sensation of pain, temperature, pressure and touch was similar for each of both local anesthetics. The regression of these sensory qualities, blocked in a dissoaciated manner, took a parallel course. With tetracaine the motor block of the lower extremities developed faster and lasted longer (Bromage 3 for bupivacaine 192 min, for tetracaine 220 min). Motor function and proprioception normalized in a synchronized manner. Isobaric spinal anaesthesia with these two solutions of local anaesthetics was found to be reliable and controllable, especially when administered to the sitting patient. Tetracaine is a good alternative to bupivacaine, currently controversial for intrathecal use.


[Plasmacortisol and parturition under epidural anaesthesia (author's transl)].

Plasma cortisol was determined by a radioimmuno assay during labour, at and after delivery in 16 primigravidas und epidural anaesthesia and was compared with 13 primigravidas, who delivered under pentazocine or pethidine and pudendal block. Cortisol levels decreased after effective epidural anaesthesia during the first stage of labor and for delivery. They increased in the control patients for delivery  and was significantly higher than in the patients under epidural anaesthesia. Two and 20 hours post partum cortisol concentrations decreased in both groups. Cortisol levels in the fetuses and newborns was markedly lower than those of mothers. At delivery, the cortisol concentration of the newborns of both groups was the same. The changes of cortisol concentrations in this study support the conclusion that epidural anaesthesia during labor and delivery reduces stress for the mother, but not for the fetus.


[Comparative studies during continuous epidural analgesia in obstetric (author's transl)].

From 1975 on, continuous epidural analgesia has been administered at the University Department of Anaesthetics in Ulm to women for pain relief during labour. One group of 350 pregnant women received bupivacaine hydrochloride, from 1. 5. 1976 to 30. 4. 1977, another group of 350 women received bupivacaine carbonate during the period from 1. 5. 1977 to 30. 11. 1977. Within these two groups the different effects of both local anaesthetic agents were compared in respect of the course of labour, the indications for epidural analgesia, the practicability of epidural analgesia, complications during labour, the rate of pain relief, the frequency of operative deliveries and the clinical condition of the newborn. The main advantages of bupivacaine carbonate for obstetric analgesia purposes are demonstrated.


[Abolition of hypotension following spinal anaesthesia by dihydroergotamine (DHE) (author's transl)].

The conduction block of the preganglionic sympathetic fibres in spina anaesthesia leads to peripheral vasodilation. Such a loss of tone in blood vessels is also pronounced on the venous side. Therefore the effects of intravenously administered DHE (10 microgram/kg i.v.) on 25 healthy patients undergoing spinal anaesthesia were studied. Though all patients were preinfused with 500 ml Ringer there was a sustained decrease in arterial and pulmonary artery pressures (p less than 0.001). However, the heart rate remained unaffected. After DHE the pressure changes were completely reversed whereas heart rate was significantly decreased (p less than 0.001). The effects of DHE can largely be explained by its powerful and selective action on the capacitance vessels in the peripheral circulation. The increased venous return to the heart augments ventricular filling. Perfusion pressure is increased without any concomitant myocardial stimulation. The results indicate that DHE can have a beneficial effect in patients undergoing spinal anaesthesia.


A pharmacokinetic approach to postoperative pain: continuous infusion of pethidine.

In an attempt to improve postoperative pain management an intravenous infusion of pethidine was designed to provide stable therapeutic blood concentrations. Ten female patients undergoing elective abdominal hysterectomy were studied. After commencement of the infusion, blood pethidine concentrations increased rapidly and exceeded 0.46 microgram/ml after four hours. The mean steady-state concentration of 0.67 microgram/ml was reached by twenty-four hours. This infusion regimen resulted in the abolition of severe pain after three hours and analgesia continued for the duration of the two day study. Significant blood concentrations of the metabolite norpethidine were found although clinically no toxic effects were observed. Side effects of pethidine were infrequent. Controlled continuous intravenous infusion of pethidine produced stable blood concentrations and provided excellent pain control.


Blood glucose changes during neurosurgery.

Blood glucose levels were studied prospectively in 40 patients undergoing elective major craniotomy. A significant (p less than 0.01) hyperglycaemic response was noted after scalp infiltration with adrenaline and incision (0.5 mmol/l) and with continued surgery (0.9 mmol/l). Patients aged 50 years and under showed a significantly greater rise with adrenaline and incision than older patients (0.8 compared with 0.4 mmol/l p less than 0.01). Preoperative high dose steroid therapy did not modify the response. Blood glucose changes were unrelated to sex, obesity, a family history of diabetes, the duration of starvation, intraoperative body temperature, anaesthetic technique, induced hypotension or blood loss.


Status epilepticus controlled by althesin infusion.

Althesin will control status epilepticus when other agents fail. Its major advantage over other agents is its lack of accumulation because it is readily metabolized. Three patients are reported and relevant literature is discussed.


Clinical report: interscalene block for shoulder operations.

Administration of adequate volumes of local anaesthetic through a single injection into the interscalene space produces blockade of both the brachial and cervical plexuses. A report of 2 patients who underwent operative repair of recurrent dislocation of the shoulder under interscalene block is presented. The advantages and disadvantages of the block for surgery around the shoulder region, and the possible complications are discussed.


Intradermal testing in the diagnosis of acute anaphylaxis during anaesthesia--results of five years experience.

Intradermal testing has been used in the diagnosis of acute anaphylactic reactions during anaesthesia in 51 patients. Positive results occurred in 32 patients and confirmation was possible in 26. Only in one case did a combination of history and intradermal testing not give a diagnosis. Nine of the negative results were confirmed. Intradermal testing is of no value in the diagnosis of reactions to local anaesthetics or colloids but has great value in determining the cause of reactions due to induction agents or muscle relaxants if performed under controlled conditions. It is safe, and requires no expertise in performance or interpretation.


Severe bronchospasm in an asthmatic patient following alcuronium and D-tubocurarine.

An asthmatic patient developed intense bronchospasm immediately following the administration of alcuronium and d-tubocurarine in the same anaesthetic. Intradermal test was positive for both of these drugs but negative for thiopentone and suxamethonium, both of which were given prior to alcuronium. The differential diagnosis and the possible mechanism of the reaction are discussed.


Beware -- the use of MAO inhibitors is increasing again.

The use of monoamineoxidase inhibitors in the treatment of depression is increasing again in Australia. This paper outlines changes in prescribing, the problems associated with monoamineoxidase (MAO) inhibitors and how they relate to the practice of anaesthesia.


A versatile antipollution device.

Removal of anaesthetic pollutants from the operating theatre environment requires the use of relatively sophisticated equipment which must be added to an existing life support system (the anaesthetic machine). The interface is only one part of this system and to be safe and satisfactory it must be as simple and versatile as possible and be designed in such a way as to render incorrect connection and use virtually impossible.


Hepatotoxicity and halothane metabolism in an animal model with application for human toxicity.

Centrilobular necrosis and a ten-fold elevation in serum alanine amino-transferase (ALT) consistently followed 2 hours of 1% halothane anaesthesia in an animal model. Conditional factors were the presence of enzyme induction and moderate hypoxia (14% oxygen), indicating an association between reductive metabolism and hepatotoxicity. Under these conditions there was at least a four-fold increase in reductive metabolites detected in the exhaled air. In clinical studies, reductive metabolites were also detected in the exhaled air of all patients examined, even after halothane anaesthesia with 100% oxygen. The amounts of reductive metabolites were comparable in man and the model, following equivalent halothane doses. It appears that a model with a similar route and rate of halothane biotransformation to man has been identified. The lesion of halothane hepatotoxicity in this model appears to be similar to that reported in man - centrilobular hepatic necrosis.


Skull growth after partial prospective lower beak extirpation in chick embryos.

On one side of chick embryos in stage 28, part of the prospective lower beak or the entire prospective lower beak anterior to the buccal corner was removed surgically (CLB-A and CLB-B embryos, respectively). In another group the prospective lower beak was split in the midsagittal plane (CMS embryos). The controls were shame-operated embryos (CS). The skulls of stage 39 CLB-A and CLB-B embryos showed changes in the lower beak as well as in the skull base, the pterygoid, the quadrate, the palatine, and the upper beak. Stage 39 CMS embryos showed shortening of the dentary and Meckel's cartilage. At the tip of the CMS mandible, an excessive amount of osseous material was found. The results support Dullemeijer's (1974) views concerning the issue of dependency of functional components. The value of a combined developmental and functional approach to morphology, i.e., integrated investigation of development of structure and function of the beaks and related jaw musculature, is discussed.


Angioarchitecture of the canine thyroid gland.

The extrinsic vasculature of the canine thyroid gland was compared to that of the human and it was considered possible that the dog does not possess a caudal thyroid artery, as often described in the literature. The thyroid capsule was relatively thin in the dog and its trabeculae appeared histologically to be continuous with the tunica adventitia of the blood vessels. The intrinsic vascular pattern simulated the lobular structure and the blood vessels were named according to their relationship, course, and major area of supply inside the gland. The veins and lymphatics were satellite to the arteries and were designated homonymously. The lymph capillaries were more closely associated to the follicular epithelium than were the blood capillaries.


[Enzyme histochemical studies on the epithelium of the epididymis of the tomcat (author's transl)].

The histochemical localization of some oxidoreductases was investigated in the epididymides of adult tomcats. Succinate dehydrogenase, lactate dehydrogenase, beta-hydroxybutyrate-dehydrogenase revealed their highest activity in corpus and cauda epididymidis whereas glucose-6-phosphate-dehydrogenase was strongest in the caput. The activity of the diaphorases and of cytochrome oxidase in the epididymal epithelium increased from caput towards the cauda epididymidis. The reaction for isocitrate dehydrogenase was distinct throughout the whole length of the ductus epididymidis. Our findings were compared with the biochemical results of other authors and the functions of the oxidoreductases in the epididymal epithelium were briefly discussed.


[Increase functions of the type dw/dt = kwm(te--t)q and their integrals (author's transl)].

In consequent continuation of the investigations into the increase functions dW/dt = kWm(En--Wn), dW/dt = kWm(E--W)n and dW/dt = ktp (E--W)n the type dW/dt = kWm(tE--t)q with q greater than 0 is added. As in the last paper, 2 cases of integration have to be distinguished, namely for m = 1 and 0 less than m less than 1 respectively. In both cases adultness W = E is reached after  a finite time tE. A quite different aspect results for the turning point of the growth function with the ordinate covering values between E/e and E for m = 1 and from 0 up to a maximum and down to E/e when 0 less than m less than 1. As in former papers graphs give an illustration of the variability of the growth curves and the increase functions. The already used example is taken up and shows a fargoing neighbourhood of the growth functions resulting from dW/dt = kWm (tE--t)q and dW/dt = ktp (E--W)n, thus hinting that quite different increase equations can lead to similar results.


The suprascapular artery: case report of an unusual origin.

A case is presented where certain branches of the right subclavian artery had unusual origins. The thyrocervical trunk was missing, the transverse cervical artery occupying its place. The inferior thyroid artery arose from the common carotid, and the suprascapular from the dorsal scapular artery. Pertinent literature on the suprascapular artery is reviewed.


[On the ultrastructure of the lacrimal gland in pigs (Sus scropha L.) (author's transl)].

The lacrimal gland of pigs has been investigated light- and electron microscopically. Among others the results are as follows: 1. The lacrimal gland of pigs is a tubuloacinar or compound acinar gland. Acini often are elongated. Tubuli and acini are enclosed in a basal lamina with some myoepithelial cells. 2. Tubuli and acini consist of mucoserous, mucous and serous cells. Mucoserous cells predominate and show secretory granules with a typical bipartite structure. 3. Like salivary glands, the lacrimal gland of pigs has a prominent duct system. Intercalated ducts have a stratified cuboidal epithelium. The cells of the proximal part contain secretory granules. The intercalated duct continues into the striated duct. Cells here are tall or columnar in shape and show basal striation, which by electron microscopy is resolved as basal invaginations of the plasma membrane with numerous elongated mitochondria in the pockets of cytoplasm so formed. Excretory ducts commence with pseudostratified columnar epithelium. 4. Terminal nerve fibres penetrate the basal lamina and make contakt with the glandular cells, the myoepithelial cells and the duct cells. The terminal axons contain abundantly synaptic vesicles, sporadic dense cored vesicles and mitochondria. Until now, we could not find any specialized presynaptic or postsynaptic membranes.


Rationale for dantrolene vs. procainamide for treatment of malignant hyperthermia.

The use of procainamide or procaine for treatment of malignant hyperthermia is commonly recommended. The skeletal muscle relaxant dantrolene has also been indicated for treatment of this complication during anesthesia. In the present study, effects of procainamide and dantrolene were compared in malignant hyperthemia-susceptible (MHS) pigs in vivo and on MHS muscle from human patients in vitro. The ED50 for dantrolene block of indirectly evoked twitch tension was 0.85 mg/kg in MHS pigs. A final cumulative dose of 2 mg/kg resulted in 68 per cent block of the twitch response. In contrast, procainamide at a final cumulative dose of 14 mg/kg had no effect on twitch response of the MHS pigs. Dantrolene, 3 micrometer, in vitro (approximately 0.8 mg/kg in vivo) was effective in preventing or reversing the abnormal halothane-induced contracture response of human MHS muscle strips. Procainamide, 0.11 mM, a dose approximating clinical levels (about 22 mg/kg), had no effect on basal twitch response or on the abnormal halothan-induced contracture of MHS human muscle. These results confirm the effectiveness of dantrolene and the lack of effectiveness of procainamide in the treatment of malignant hyperthemia.


Halothane hepatotoxicity and fluoride production in mice and rats.

Other investigators have demonstrated halothane-induced hepatic injury in rats anesthetized in hypoxic environments. The authors examined this phenomenon in mice and investigated plasma fluoride levels in mice and rats anesthetized with halothane in 40, 21 and 7 per cent oxygen with or without pretreatment with phenobarbital or carbon tetrachloride. They found no hepatic necrosis in mice. Mice produced less fluoride than rats. This difference in halothane metabolism between Sprague-Dawley rats and Swiss-Webster mice may explain the failure to observe hepatic necrosis in mice.


Halothane-induced renal vasodilation.

Halothane-induced changes in renal function have generally been attributed to alterations in systemic hemodynamics, sympathetic tone, and various hormones. Studies were performed to determine whether halothane directly affects the kidney. Twenty-one canine kidneys were perfused in vitro utilizing hemodilution, pulsatile flow, and membrane oxygenation. Temperature and arterial blood-gas variables were controlled and mean and pulse pressures were maintained. Four experimental periods (I-IV)(each consisting of two 10-min sample collection periods) were conducted, with a 20-min "rest" period between succeeding experimental periods (elapsed time = 140 min). Responsiveness was assured by obtaining a normal response to furosemide, acetylcholine, or epinephrine after Period IV. In eight additional kidney preparations halothane was administered to achieve either a "low" (17 +/- 3 mg/100 ml) or "high" (35 +/- 5 mg/100 ml) concentration in Period II, the sequence reversed for Period III, and halothane eliminated by Period IV. Halothane produced marked increases in blood flow (21-26 per cent), total (203-267 per cent) and fractional (173-179 per cent) sodium excretion, osmolal clearance (62-111 per cent) and urinary volume (130-161 per cent). These changes were associated with a shift of microspheres from outer to inner cortex, and were completely reversible by eliminating the halothane. In the absence of external influences, halothane produces renal vasodilation and natriuresis. Direct tubular depression cannot be ruled out.


Alteration by enflurane of Electrophysiologic correlates of search in short-term memory.

Effects of controlled subanesthetic concentrations of enflurane on short-term memory functions and associated scalp evoked potentials were studied in eight male volunteers. Short-term memory processes were assessed through a search task. A series of digits (one, three, five, seven, nine, or 11 digits in each series) was presented visually, followed by a test digit, which in half of the trials was part of the series, and in half of the trials was not. The subject responded by pressing one of two switches, signalling "yes" or "no" accordingly. Averaged evoked potentials elicited by the test digit were obtained from seven sites on the scalp. End-tidal enflurane concentrations between 0.12 and 0.25 per cent increased significantly by 30-40 msec the latency of the components of the evoked potentials reflecting sensory processing, but did not affect their amplitude significantly. This increase could not explain the 287-msec increase in reaction time. Amplitude of late components of the averaged potential reflecting information processing was markedly decreased, which the authors interpret as indicating increased trial-to-trial variation in latency of the late component. The authors conclude that enflurane delays and introduces variance into the short-term memory processes and subsequent decision processes that preced overt responses.


Morphine decreases peripheral vascular resistance and increases capacitance in man.

The response of the human peripheral circulation to morphine in large doeses independent of cardiac and respiratory influences has not been delineated. In 28 patients during cardiopulmonary bypass, alterations of peripheral vascular resistance (PVR) and capacitance in response to rapid arterial injection of morphine, 0.5 mg/kg or 1 mg/kg alone, or preceeded by promethazine, 1 mg/kg, naloxone, 10 mug/kg, or naloxone, 20 mug/kg, were recorded over 15 min at a constant perfusion rate. Both doses of morphine decreased PVR by 46 percent at 2 min, with values returning to control at 9 min. When promethazine preceded morphine, the decrease in PVR after morphine was 25 percent. Naloxone did not alter the response. An increase in capacitance of 600 ml observed 5 min after morphine administration did not revert to control after 15 min, and was unaltered by prior administration of naloxone.


Humidity and the anesthetized patient.

Damage to the ciliated cells of the tracheobronchial tree and incidence of postoperative pulmonary complications were measured by point-scoring systems in 202 patients who breathed dry and humidified anesthetic gases for 225 +/- 78 min. The incidence of postoperative pulmonary complications decreased as the humidity of administered anesthetic gases increased from 0 to 32.5 mg H2O/l. A similar relationship was found between the amount of inhaled moisture and the damage to the ciliated epithelium of the tracheobronchial tree. These results appear to indicate that a high inspired humidity is beneficial for operations on normothermic patients, and that cellular damage caused by dryness is a possible contributory factor in the production of the pulmonary atelectasis that follows stoppage of the mucociliary transport system in the immmediate postoperative period.


Pre- and postsynaptic effects of pancuronium at the neuromuscular junction of the mouse.

The dose-effectiveness of pancuronium as it relates to membrane potentials, action potentials, electrical membrane constants, miniature endplate potentials, endplate potentials, and quantal release was studied in murine phrenic nerve-diaphragm preparations in vitro. Emphasis was placed on comparison of presynaptic with postsynaptic effects of pancuronium under similar experimental conditions. At low concentrations of pancuronium (5 X 10(-8) g/ml or less), no presynaptic effect was found. At high concentration (5 X 10(-7) g/ml), pancuronium depressed quantal release to 26 per cent of control in cut-fiber preparations and 40 per cent of control in high-magnesium preparations. Postsynaptic effects as measured by the amplitude of miniature endplate potentials and relative depolarization induced by 20 microns carbachol, revealed depression to 16 and 22 per cent of control, respectively, at a pancuronium concentration of 5 X 10(-7) g/ml. Pancuronium had no effect on directly elicited action potentials and electrical membrane constants. The authors conclude that presynaptic as well as postsynaptic effects of pancuronium in paralytic doses are essential in contributing to the total efficacy of neuromuscular depression.


Atrioventricular conduction in dogs during anesthesia with isoflurane.

The effects of 1.25, 2.0, and 2.5 MAC isoflurane on atrioventricular conduction were studied by His-bindle electrocardiography during atrial pacing in ten dogs. No effect upon atrioventricular conduction as evidenced by changes in A--H interval (the time of conduction from low right atrium to His-bundle, representing primary AV nodal conduction) was found at these concentrations. Atrial pacing to 200 beats/min did not influence the A--H interval at the three anesthetic concentrations. The stability of cardiac rhythm observed clinically with isoflurane may be related to this lack of effect upon the AV node.


A method for sampling halothane and enflurane present in trace amounts in ambient air.

A method for the sampling of small amounts of halothane and enflurane in ambient air is described. Sampling is performed by drawing air through a sampling tube packed with Porapak Q, which absorbs the anesthetic agent. The amount absorbed is determined by gas chromatography after thermal desorption. This method can be used for "spot" or personal sampling or for determining mean whole-room concentrations over relatively long periods (several hours).


Chronic exposure to low concentrations of halothane-nitrous oxide: lack of carcinogenic effect in the rat.

The effects of prolonged exposure to low-concentration combinations of halothane and nitrous oxide on tumor incidence, especially with regard to the reticuloendothelial system, were studied. Three groups of 50 male and 50 female Fischer 344 rats each were studied. For seven hours/day, five days/week, for 104 weeks, Group I was exposed to filtered air (control); Group II, to halothane, 1 ppm, and nitrous oxide (N2O), 50 ppm; Group III, to halothane, 10 ppm, and N2O, 500 ppm. No evidence of exposure-related effects on body weight, appearance, behavior, survival, or hematologic findings was found. Histologic evaluation of the reticuloendothelial system and of other major organs revealed neither enhancement of the spontaneous tumor rate nor any unusual neoplasm. Thus, this study did not lend support to the hypothesis that these anesthetic agents in low concentrations are responsible for the reportedly higher than average incidence of reticuloendothelial malignancies in operating room personnel.


Indices of myocardial oxygenation during coronary-artery revascularization in man with morphine versus halothane anesthesia.

A prospective study in 12 adult male patients undergoing coronary-artery revascularization was conducted to compare the effects of a morphine versus a halothane anesthetic technique on several indices of myocardial oxygen supply and demand. Indices reflecting myocardial contractility, preload, afterload, and heart rate were measured. Undesirable increases in systemic and pulmonary capillary wedge pressure were minimized using sodium nitroprusside as needed. In the period after sternotomy but before revascularization, patients anesthetized with morphine (mean 2.1 mg/kg) had significant (P less than .05) increases in rate-pressure product, tension-time index, blood pressure, and heart rate, as well as relative myocardial ischemia, evidenced by significant ST-segment depression in the V5 lead of the EKG and a decreased diastolic pressure-time index/tension-time index compared with patients anesthetized with halothane (mean .75 per cent inspired). Few difficulties associated with myocardial depression were seen in patients anesthetized with halothane. Halothane, at least in a well-monitored environment, is safe for use in patients without severe ventricular dysfunction undergoing coronary-artery revascularization.


Sites and mechanisms of action of halothane on skeletal muscle function in vitro.

In isolated rat diaphragm strips, halothane augments the tension produced during caffeine-induced contractures in a dose-related manner. Potassium-induced contracture tension is augmented in the presence of halothane to a concentration of 0.75 per cent, and decreased at halothane concentrations of more than 1 per cent. The time of peak tension for potassium-induced contractures is diminished by all halothane concentrations. T-tubular disruption by hypertonic glycerol does not alter anesthetic-induced augmentation of caffeine-induced contractures. It is postulated that halothane augments calcium-release processes in sarcoplasmic reticulum. Membrane events or excitation-contraction coupling steps may be also altered by halothane.


PEEP and CPAP following open-heart surgery in infants and children.

The cardiorespiratory effects of 5 cm H2O end-expiratory pressure were studied in 22 infants and children an hour after open-heart surgery during mechanical ventilation with positive end-expiratory pressure (PEEP) and prior to endotracheal extubation approximately 15 hours later during spontaneous breathing (CPAP). Thermodilution cardiac output determinations and respiratory airflow, volume and pressure recordings were made to assess the effects of airway pressure changes on the respiratory waveform and oxygen delivery. Neither PEEP nor CPAP had a significant effect on cardiac output, intrapulmonary shunting, oxygen consumption, or oxygen utilization. Patients who had had pulmonary hypertension preoperatively did not behave differently from those without pulmonary hypertension when removed from ventilatory supprot. Expiratory airflow was significantly prolonged when positive end-expiratory pressure existed during both controlled and spontaneous respiration. During CPAP, this "expiratory braking" was associated with an increase in tidal volume and decreases in respiratory rate and minute volume. Because of the lack of improvement in cardiopulmonary function in this group of patients, and the possibility of untoward effects from sustained end-expiratory pressure, PEEP and CPAP might properly be reserved as temporary supportive techniques should respiratory function be compromised.


Porphyrin-inducing activity of alfaxolone and alfadolone acetate in chick embryo liver cells.

The two steroid components of Alfathesin, alfaxolone and alfadolone acetate, have been tested for porphyrin-inducing activity in chick embryo liver cell culture and for hepatic ALA-synthetase-inducing activity in the 17-day-old chick embryo. In cell culture alfoxolone was shown to have potency comparable to that of thiopental, while alfadolone acetate had low potency. In the 17-day-old chick embryo alfaxolone has a third the potency of thiopental; alfadolone acetate showed low potency. The authors conclude that an induction dose of Alfathesin would be less likely than a comparable dose of thiopental to increase ALA-synthetase activity in a patient with hereditary hepatic porphyria.


Restoration of muscle-pump function in chronic venous insufficiency.

The direct venous pressure profile was recorded before and after treatment in 15 patients suffering from chronic venous insufficiency. Patients were treated conservatively, first by tight elastic support and walking exercises, then by eliminating the points of blood shunting by sclerotherapy of the incompetent perforators. The average venous pressure drop during tiptoeing was increased from 31.6% to 50.9% (P less tan 0.01), and the time required for return to the resting venous pressure level increased from an average 6 seconds to 12.9 seconds (P = 0.01). These values indicate a significant improvement in the functioning of the muscle pump of the calf, and are paralleled by clinical and subjective improvement. Wr recommend this method of treatment in cases of chronic venous insufficiency. We also wish to point out the importance of repeated direct venous pressure profile recording as a means of assessing the effectiveness of treatment in cases of venous disorders.


Angiotensin-converting enzyme inhibitor (SQ 20881) in the diagnosis of renovascular hypertension.

SQ 20881, an angiotensin-converting enzyme inhibitor, was given to 12 patients with renovascular hypertension and to 1 patient with unilateral parenchymatous renal disease in order to evaluate the role of renin-angiotensin systems in their hypertension. Plasma renin activity (PRA) and aldosterone were assayed in systemic blood before and after the injection of SQ 20881. In 5 patients PRA was also measured separately in each renal vein. Blood pressure decreased, PRA increased, and aldosterone level decreased in the 12 renin-dependent patients. When PRA was sampled separately from each renal vein, the increase was larger on the side of the affected kidney. Four patients with a positive test underwent corrective surgery, and in all blood pressure became normal. SQ 20881 is a useful agent in evaluating the contribution of renin in patients with hypertension.


Cerebral aneurysm induced by giant cell arteritis: a case report.

A rare case of giant cell arteritis inducing an aneurysmal dilatation in the peripheral branch of the middle cerebral artery was presented. The lesion was solitary and no extra-cerebral vasculature was involved. The literature of giant cell arteritis and of similar disorders involving the intracranial arteries was reviewed.


Hyperkalemia-induced conversion of chronic atrial fibrillation to normal sinus rhythm; a case report.

The electrocardiographic manifestations of hyperkalemia have been well described. We report a patient with chronic congestive heart failure and atrial fibrillation for 6 years. who converted to sinus rhythm during an episode of hyperkalemia. To our knowledge, this is the first report of hyperkalemia-induced conversion of chronic atrial fibrillation to sinus mechanism.


Anastomotic rupture of aortic grafts.

Proximal suture line disruption is one of the severe complications of synthetic vascular grafting for arteriosclerotic aortic disorders. The pathology of clinical and experimental cases revealed that a small bite of each stitch cut into the host aorta and became disrupted. Making each stitch as large as possible in the host aorta is the first procedural choice for aortic replacement surgery. Protecting the anastomotic line with a synthetic mesh cloth wrapping is preferable.


Compression therapy of vein and lymph vessel diseases of the lower extremities: a present day overview.

Compression therapy of vein and lymph vessel diseases of the lower extremities has been used for over 2 1/2 millenia. A short historic survey is given. The theoretic basis is to prevent edema by helping the pump action of the calf muscles reverse the pathologic caudad blood flow upward toward the vena cava inferior, and to attempt to fix a fresh thrombus in the calf veins and thus prevent pulmonary embolism. The available material, including bandages, elastic stockings, the technique, indications, complications, and especially allergic skin reactions are discussed.


Thrombophlebitis associated with vitamin E therapy. With a commentary on other medical side effects.

I have encountered 50 patients with clinical thrombophlebitis involving the lower extremites, with or without associated edema and pulmonary embolism, in whom longstanding self-medication with large amounts of vitamin E appeared to be a significant factor. The majority improved following cessation of vitamin E. In view of the epidemic nature of thrombophlebitis and deep vein thrombosis in the United States, the presumed innocuousness of vitamin E therapy requires reevaluation. Other clinical side effects also have been noted in patients receiving large doses of vitamin E. They include breast tenderness, elevation of blood pressure, a fatigue syndrome, myopathy, intestinal cramps, urticaria, and the possible aggravation of diabetes mellitus. The influence of concomitant metabolic, endocrine, and cardiovascular disorders on the thrombogenic potential of vitamin E is raised, and several possible mechanisms conducive to thrombophlebitis are reviewed.


Surgical management of venous stasis disease: an update.

The management of leg ulcers of venous origin begins with patient cooperation. Bed rest, leg elevation, and local care should relieve pain and initiate healing. This can be facilitated or managed on an outpatient basis by using an Unna's boot. Superficial varicosities should be ligated and stripped, and perforators identified by venography should be ligated and divided subfascially. Ulcers can then be excised and grafted. Long-term care includes chronic use of compression hose.


Wedged hepatic venous pressure in congential heart disease.

Seventy cases of congential heart disease including the most frequent types were studied, and wedge hepatic venous pressure (WHVP) was measured in each. The mean pressure was determined in the "jammed position" and in the free hepatic veins, inferior vena cava, and low right atrium. The average mean WHVP was 7.0 mm Hg, 5.0 in inferior vena cava, and 3.4 in the right atrium. A direct relationship was found between wedge hepatic venous pressure of the inferior vena cava and the low right atrium, but not other parameters. Ten patients had a mean pressure above 10 mm Hg. We believe that in many circumstances in patients with congenital heart disease, liver function may be abnormal and high values of wedge hepatic venous pressure may also be found.


Progression of a dural arteriovenous malformation resulting in an intracerebral hematoma. A case report.

A progressing, essentially extracranial arteriovenous malformation with purely external carotid feeders can involve the intracranial vasculature by enlargement of its drainage area. Thus it can cause cerebral dysfunction by an intracranial bleed or raised intracranial pressure due to venous engorgement. A case is described to support this possibility.


Right coronary arteriocameral fistula into the right ventricle. An inspiratory accentuation of continuous murmur: a case report.

A case of a right coronary artery fistula into the right ventricle is presented. The clinical diagnosis was based on the presence of a continuous murmur best heard in the epigastrium, which increased in intensity and duration on inspiration . This report stresses the importance of this sign in the localization of the arterial fistula to the right ventricle. To the best of our knowledge, there are no previous reports of this sign.


Prinzmetal's variant angina associated with subarachnoid hemorrhage: A case report.

Prinzmetal's variant of angina occurred in a 48-year-old man who sustained two attacks of subarachnoid hemorrhage within 10 days. The first anginal pain started at the same time that the second cerebrovascular accident developed, but subsequent anginal episodes were not accompanied by other symptoms or signs that indicated new development of subarachnoid hemorrhage. Twelve days later, when nuchal rigidity was fairly improved, the episodes of chest pain ended. A vasospasm of the large coronary arteries--probably due to the derangement of the autonomic nervous system caused by subarachnoid hemorrhage--was presumed to contribute to the occurrence of the variant angina. Based on this case and on review of the literature, we propose that coronary arterial spasm is one of several causes of the cardiac changes seen in subarachnoid hemorrhage.


A comparison of the bronchodilator effects of terbutaline, Tedral and the simultaneous use of both agents.

A modified double-blind study in 14 asthmatic patients had demonstrated that oral terbutaline (5 mg) resulted in significantly greater bronchodilation than did Tedral. Simultaneous ingestion of terbutaline and Tedral resulted in significantly greater bronchodilation than after either agent alone, which supports the concomitant use of beta-2 agonists and theophylline agents when treating patients with airflow obstruction.


The use and interpretation of RAST to stinging insect venoms.

Quality controlled, standardized RAST systems for five stinging insect venoms are described. These systems were evaluated using 375 sera from insect reactive patients from six diverse geographic regions. Ninety-four percent of patients with recent histories of systemic allergic reactions to stings were positive to at least one venom while 4 percent of normal local reactors were positive. The cross reactions between honey bee and vespid venoms were studied by RAST inhibition. A quantitative method for interpretation of venom RAST is presented to account for cross-reactivities and the approach to diagnosis is discussed.


Respiratory allergy to algae: clinical aspects.

A comprehensive investigation was done to evaluate the allergenic algae in the Delhi area. Results of 4,000 skin tests performed on 400 patients suffering from naso-bronchial allergy and 300 skin tests on 30 healthy persons with 10 common algae isolated from the Dehli atmosphere are presented and compared. Positive skin reactions (1+ to 3+) to algae extracts ranged from 25.7% with Lyngbya major extract to 1.7% with Oscillatoria simplicissima extract; in healthy non-allergic volunteers there were no positive skin reactions. The Prausnitz-Küstner (PK), bronchial provocation and conjunctival tests were negative in patients with negative skin reactions; in patients with positive skin reactions PK was positive in 70.9%, bronchial provocation in 50% and conjunctival in 48.5%. Levels of total IgE in patients with naso-bronchial allergy were higher, ranging from 1,225 international units per ml to 1,550 international units per ml, while in healthy volunteers the values were less than 885 international units per ml.


The effect of "warm-up" on exercise-induced asthma.

To determine the effect of "warm-up" on exercise-induced asthma (EIA) 18 subjects ( mean age 19.7 years) performed five minutes of submaximal treadmill running to achieve a heart rate (HR) of 85% of predicted maximum for age. One such exercise test was preceded by "warm-up" and one was not. "Warm-up" consisted of three minutes of treadmill walking or jogging to attain 60% of predicted maximun HR for age. An identical incidence (77.8%) and severity (38.1% mean decrease in FEV1) of EIA was recorded after treadmill running whether preceded by "warm-up" or not. While this study does not support the concept that "warm-up" could reduce the likelihood of EIA, it is recommended that a longer, more intense "warm-up" involving interval exercise should be evaluated before rejecting the view that "warm-up" ameliorates EIA.


Farmer's lung disease: long-term clinical and physiologic outcome.

To determine the long-term effects of farmer's lung disease and the factors influening the outcome, 141 patients with farmer's lung disease were evaluated. At the time of the last follow-up, 29 patients had died and 92 (mean age, 54 years) were studied clinically, physiologically, and radiologically. The mean length of disease was 14.8 years (range, 2.25 to 40 years). Symptoms at the time of the last follow-up included complaints of cough (33 per cent of the patients), breathlessness while walking on the level (20 per cent), breathlessness on minor exertion (14 per cent), and breathlessness while at rest (3 per cent). Twenty-eight per cent had chronic bronchitis. Thirty-nine per cent (36 of 92 patients) had some evidence of interstitial changes on roentgenogram. Abnormal vital capacity was present in 11 patients (12 per cent), abnormal total lung capacity in 11 (12 per cent), and abnormal CO difussing capacity in 27 (30 per cent). The ratio of one-sec forced expiratory volume to forced vital capacity was abnormal in 23 patients (25 per cent), and arterial PO2 was abnormal in 39 (40 per cent). Patients with a history of 5 or more symptomatic recurrences had significantly smaller values (P less than 0.05) for vital capacity, total lung capacity, and CO diffusing capacity than did those patients with less than 5 recurrences. There was no significant relation between continued farming or length of disease and lung function. On the basis of several measurements of airway function, 34 of the patients (58 per cent) were found to have some abnormality, It is concluded that symptomatic recurrences may be the most important factor in determining the danger of progressive disease. Persistently positive precipitins were correlated with decreased CO diffusing capacity. Moreover, airway disease is relatively uncommon but does occur, and in some cases it is a possible consequence of farmer's lung disease.


Comparison of respiratory variables in grain elevator workers and civic outside workers of Thunder Bay, Canada.

We compared respiratory variables in 441 grain elevator workers with 180 civic outside laborers in Thunder Bay. The grain handlers had a lower frequency of both positive skin reactions to pollens and molds and a family history of asthma, which suggests that they may have been self-selected for a decreased tendency to develop allergic respiratory disease. There was a higher frequency of cough and rales and a small decrease in forced vital capacity and forced expiratory volume in one sec among the grain handlers, as compared to the civic workers matched for smoking. However, these differences between grain and nongrain workers were small in comparison to those between smokers and nonsmokers. There was no clear indication of a worsening of respiratory functions that could be attributed specifically to duration of employment as a grain elevator worker.


Decrease in lung recoil pressure after cessation of smoking.

Tests of lung mechanics and single-breath carbon monoxide diffusing capacity (DLCO) were done in 26 apparently healthy cigarette smokers before and 2 months after cessation of smoking. There was a significant increase in vital capacity and 1-sec forced expiratory volume as well as improvement in frequency dependence of lung dynamic compliance. Slope and phase III and density dependence of maximal expiratory flow showed a borderline improvement DLCO did not change. Static lung pressure-volume curves showed a small but significant (P less than 0.01) shift toward lower pressures. We concluded that the previously reported decrease in lung recoil pressure observed in smokers is even more accentuated after cessation of smoking.


Arterial blood gas tension changes at the start of exercise in chronic obstructive pulmonary disease.

In a previously reported study of a group of normal subjects, large decreases in arterial O2 tension (PaO2) of as much as 37 mm Hg were measured during the first 90 sec of slow stair-climbing exercise (chosen as a common daily exertion). This study reports the changes in PaO2, arterial CO2 tension (PaCO2), and ventilation in 7 patients with chronic obstructive pulmonary disease and resting hypoxemia during the first 90 sec of similar exercise. The patient group showed significantly smaller unsteady-state decreases in PaO2 starting from a smaller resting value (patient group, 72 +/- 2.6 mm Hg, mean +/- SE; normal group, 92 +/- mm Hg; P less than 0.001) and decreasing to a similar smallest value (patient group, 58 +/- 3.8 mm Hg; normal group, 65 +/- 3.4 Hg; P greater than 0.05). PaCO2 tended to oscillate around the resting value in both the patient group and the normal group, and the rates of increase in ventilation in the 2 groups were similar. The physiologic processes that could limit the unsteady-state decrease in PaCO2 in the patient group are analyzed, the analysis suggesting that a slower rate of increase in tissue consumption of O2 is most likely to account for the smaller decrease in PaO2.


Immunoglobulin concentrations in serum and nasal secretions in chronic obstructive pulmonary disease. A matched-pair study.

Immunoglobulin concentrations were determined in the sera and nasal washes of 111 patients with chronic obstructive pulmonary disease who were 45 to 60 years of age and in 111 control subjects matched with the patients for age, sex, occupation, and smoking history who demonstrated normal 1-sec forced expiratory volume. Serum IgA, IgM, IgG, nad IgE were not significantly different in the 2 groups. Serum IgD was significantly higher in subjects with chronic obstructive pulmonary disease. Nasal wash IgD and IgM, expressed as percentages of total protein, were higher in index cases, but nasal wash IgA and IgG were comparable in both groups. The finding of relatively high concentrations of IgA, expressed as fractions of total protein, in respiratory secretions compared to serum is consistent with earlier findings that IgA is actively secreted from the respiratory epithelium and is not deficient locally in subjects with chronic obstructive pulmonary disease. In contrast, IgM and IgG expressed as proportions of total protein were consistently higher in sera than secretions. The IgE in nasal secretions was detected so seldom in this study that too few matched pairs were available for statistical analysis. The higher concentration of IgD in the serum and nasal secretions of patients with chronic obstructive pulmonary disease compared with their matched pairs and the associated higher frequency of low IgD in control subjects suggests that low IgD may be protective against the development of chronic obstructive pulmonary disease. Further studies on the biologic role of IgD may provide better understanding of these findings.


Maximal expiratory flows after postural drainage.

Flows measured from maximal expiratory flow-volume (MEFV) curves were used to evaluate the efficacy of postural drainage in improving ventilatory function acutely. Maximal expiratory flow-volume curves were obtained for 9 cystic fibrosis subjects and 10 subjects with chronic bronchitis before and 5, 15, and 45 min after a 30-min session of postural drainage with percussion, vibration, and coughing. Forced vital capacity (FVC) was significantly increased 45 min after drainage for the combining group. Flows at high lung volumes were different for the 2 subgroups. Subjects with cystic fibrosis demonstrated a significant increase in peak expiratory flow rates 45 min after drainage and an increase in forced expiratory volume in one sec at all time intervals. The subjects with chronic bronchitis had a decreased peak expiratory flow rate 5 min after drainage, but by 45 min, it had returned to baseline. There was no significant change in one-sec forced expiratory volume at any time interval for the chronic bronchitis subgroup. Changes in flows at low lung volumes were similar for the 2 subgroups. Forty-five min after drainage there was an increase in flow rates near 50 per cent of FVC. Flows near 25 per cent of FVC were increased 15 and 45 min after drainage. This study demonstrated that postural drainage with coughing resulted in significant improvement in flows at low lung volumes. Changes in flows at high lung volumes were less consistent.


Respiratory and nonrespiratory effects of doxapram in congenital central hypoventilation syndrome.

Doxapram is a respiratory stimulating drug that affects both peripheral chemoreceptors and medullary respiratory and nonrespiratory neurons. We administered doxapram 60 2 infants with congenital central hypoventilation syndrome. In 6 separate trials at a dose range of 0.32 to 2.0 mg per kg of body weight per min, quiet-sleep tidal volume increased from 4.9 +/- 1.0 to 8.5 +/- 0.9 ml per kg of body weight, minute ventilation increased from 140 +/- 38 to 286 +/- 31 ml per kg of body weight per min, and alveolar PCO2 decreased from 60 +/- 5 to 32 +/- 2 mm Hg. In all instances, the maximal quiet-sleep ventilatory response was achieved within 10 min. The ventilatory response to steady-state CO2 breathing was not improved with doxapram. A continuous infusion of doxapram for 5.2 days in one infant successfully maintained normal quiet-sleep ventilation. In both infants, multiple nonrespiratory effects of doxapram occurred; enteral administration was associated only with generalized neuromuscular stimulation, but the 5-day intravenous infusion was also associated with acute hepatotoxicity and a perforated duodenal ulcer. The medullary respiratory neurons in central hypoventilation syndrome may be incapable of responding to doxapram, and the ventilatory responses observed may be due entirely to stimulation of peripheral chemoreceptors. Although quiet-sleep ventilation can be successfully maintained with intravenous and enteral administration of doxapram, and tachyphylaxis has not been observed, we have been unable to avoid at least the neuromuscular manifestations of nonrespiratory medullary stimulation.


Comparison of various methods for reading maximal expiratory flow-volume curves.

To determine the best procedure for reading maximal expiratory flow-volume curves 2 sets of 5 curves were obtained one hour apart in 89 subjects and processed digitally according to 8 different methods. Four indices were considered: the forced expiratory flows at 25, 50, and 75 per cent of the forced vital capacity, and the maximal mid-expiratory flow. When selecting the curve yielding the largest forced vital capacity or the largest sum of forced vital capacity and forced expiratory volume in 1 sec, flow values were significantly lower (P less than 0.001) and were often less reproducible than those obtained with most of the other methods. Computing the mean of the indices among the curves with the 2 largest forced vital capacities also provided comparatively low values, but with with better reproducibility. In contrast, maximal flows were probably overestimated by using the highest values among the curves having forced vital capacity or a surface area within 5 per cent of the largest, or when reading the indices on a composite curve obtained by superimposing individual breaths at residual volume. More reproducible and, probably, unbiased data may be drawn from the composite curves obtained by superimposing the breaths either at total lung capacity or on the descending limb.


Impaired alveolar macrophage chemotaxis in patients with acute smoke inhalation.

Pulmonary infection is a leading cause of death in patients with smoke inhalation; however, few studies have evaluated the effects of inhaled smoke on the host defense mechanisms of the lung. In this study we investigated the effects of acute smoke inhalation on the random and chemotactic (stimulated unidirectional) migration of human pulmonary alveolar macrophages. Fiberoptic subsegmental pulmonary lavage was performed in 19 normal subjects (12 nonsmokers and 7 smokers) and 7 patients with smoke inhalation. After quantification of lavaged cell populations, random and chemotactic migration was measured using modified Boyden chambers. Zymosan-activated serum was used as a chemotactic stimulant. Mean +/- SE random migration was 6.2 +/- 0.8 cells per 20 microscopic fields in smoking control subjects, 5.7 +/- 0.7 in nonsmoking control subjects, and 5.2 +/- 0.7 in patients with smoke inhalation. These values are not significantly different. In contrast, the mean directed (chemotactic) migration of pulmonary alveolar macrophages was 26.5 +/- 1.9 in smoking control subjects, 22.7 +/- 3.0 in nonsmoking control subjects, and 11.4 +/- 1.4 in patients with smoke inhalation; the latter response was significantly different from that of the smoking (P less than 0.001) and nonsmoking (P less than 0.025) control subjects and the combined average of the 2 control groups (P less than 0.001. In vitro exposure of pulmonary alveolar macrophages to nontoxic doses of smoke produced similar impairment of chemotaxis. These findings may partially explain the enhanced susceptibility of patients with smoke inhalation to pulmonary infection.


Accuracy sensitivity to carboxyhemoglobin, and speed of response of the Hewlett-Packard 47201A ear oximeter.

We have shown that the Hewlett-Packard 47201A ear oximeter measures arterial O2 saturation within 95 per cent confidence limits of +/- 4 per cent when arterial blood saturation is more than 65 per cent, but at lower saturations the oximeter consistently provides a reading that is too low. The oximeter is sensitive to carboxyhemoglobin, progressively overestimating arterial saturation as carboxyhemoglobin concentration increases from 0 to 18 per cent. The time response is exponential, with a normal time constant of 3 sec, but this is halved in the fast mode or operation.


The timing of the forced vital capacity.

Based on analysis of more than 2,500 forced vital capacity (FVC) maneuvers, we examined 2 aspects of the standards for spirometry recommended by the 1977 Snowbird Workshop concerning the timing of the FVC maneuver. We compared the forced expiratory volume in one sec (FEV1) when timing was initiated by the back extrapolation method with FEV1 when timing was initiated by flow or volume threshold to determine whether the latter offered a reliable equivalent. Although the mean differences appear to be relatively small, because of variability in initiating expiratory effort, neither alternative is likely to offer a uniformly accurate numeric equivalent to backward extrapolation. We also measured the volume expired before the initiation of the timing as a per cent of FVC to determine whether 10 per cent was a reasonable limit to apply for acceptability of a test. Although 2 SD from the mean of 4.35 per cent were well within this limit, it appears that the technician's judgment of acceptability is sufficient in most cases.


Two-year mortality in 760 patients transported by helicopter direct from the road accident scene.

Of 760 direct admissions to a specialized trauma center, 173 (22.7%) victims of motor vehicle accidents died. Excluding patients dead on arrival, the mortality rate was 14.5%. Autopsy reports were reviewed and showed that the major cause of death was head injury (49.7%). Uncontrollable hemorrhage from massive trauma was the next most common problem and usually proved fatal in the first 24 hours after admission. The incidence of sepsis and renal failure increased with prolongation of CCRU stay. Following admission, respiratory failure was not a common cause of death (3%). Because of direct helicopter rather than ambulance transport from the scene of the motor vehicle accident, earlier attention was paid to diagnosis of trauma and treatment of respiratory insufficiency with mechanical ventilation. Because of the early initiation of therapy, there was rapid restoration of circulating volume and tissue perfusion. This may account for the low mortality.


Radiology and the massive trauma victim.

The radiologic protocol as presented above has evolved over a period of several years. It is currently is use, and with only rare exceptions, has been found to be completely adequate for the massively traumatized patient. Its most important aspect is that practically no time is expended in the radiologic assessment of the patient.


Head injury and the dilated pupil.

The significance of the dilated pupil in head injury is discussed. History of this condition and its possible mechanisms are described. Three patient reports are presented with unilateral dilated pupil. The literature on the subject is reviewed. Finally, the diagnostic steps which may be taken to differentiate direct third nerve injury from expanding mass lesion are suggested.


External fixation of facial fractures.

Although external fixation is not indicated in every type of facial fracture, its use alone or with intermaxillary or internal fixation may be of benefit with problems resulting from avulsed segments, infection, inadequate previous reduction, delayed reduction, severe displacement and comminution, non-union, cerebrospinal fluid leak or where a combination of these factors exists. The judicious application of extraskeletal fixation can save valuable anesthetic time as well as assure accesibility of the pharynx and maintenance of an airway and routes for nutrition when these might otherwise be compromised. Although extraskeletal fixation is not withou problems or contraindications, it must be weighed in view of the patient's physical, mental and neurological status, and the existence of concomitant injuries.


Motor classification of spinal cord injuries with mobility, morbidity and recovery indices.

In this article, we have presented a new motor classification of patients with spinal cord injuries. This system of classification provides statistically discrete subdivisions. The patients in each of the subdivisions of the classification can be mathematically summarized with numerical indices which then may be accurately analyzed statistically. This allows the clinical researcher in spinal cord injuries to evaluate current treatments and assess the potential of new treatments and assess the potential of new treatment regimes. In addition, tables of MIi and recovery rates have been presented to aid in the correct classification of new patients and in the prediction of their present chances of motor recovery. Last, we have introduced a standardized motor examination, based on past experience, that will aid in the direct comparison of future results for any spinal cord treatment regimes.


Changing patterns of posttraumatic acute renal failure.

ARF will continue to occur as more severely traumatized patients survive with better resuscitation. The incidence of ARF, however, appears to be steadily decreasing and ARF occurs only in patients with severe injury and multiple organ failure. ARF developing for the past three years in MIEMS was a nonoliguric variety in the majority of patients. Management of ORF with dialysis has been disappointing. Prevention of oliguria in ARF appears possible and may be one of the most important steps to decrease the morbidity and fatality rate. Further investigation is required to find the cause and optimum management of NORF.


Rehabilitation of the trauma patient.

Many rehabilitation methods are directed at prevention during the acute management of the trauma patient. Their success is measured by the absence of secondary disabilities. Their cost in relation to health care can be estimated. Figures from 1972 showing cost estimates for treatment of common complications are as follows: Decubitus ulcers $7,000, Urinary tract infection 5,000, Kidney stones 5,000, Thrombophlebitis with pulmonary embolism 4,000, Pneumonia 3,000, Contractual deformities 2,000. Current inflation would revise the above costs at least 25%. It is also important to note that the cost of such complications to the individual is immeasurable in time and energy and quality of life.


The unexpected increase of serum insulin levels in patients soon after trauma.

Serum insulin values elevated above the normal fasting range, i.e., 19.0-43.4 microU/ml (mean 27.9 +/- 6.4) were found on admission in 18.2% of patients with various forms of acute injury. Concomitant mean serum glucose level was 184 +/- 59 mg/100 ml compared with 81 +/- 6 mg/100 ml found in overnight fasting normal subjects. In this group of patients, the mean and the highest insulin elevations above the control mean value were 170% (85 microU/ml) and 940% (290 microU/ml) respectively. In individuals admitted directly from the scene of an accident, the mean insulin increase was significantly smaller (95%; p less than 0.01) than in patients transferred from other hospitals-203% (68 microU/ml ) in contrast to 940% (290 microU/ml) found in the transfer subgroup. Mean serum glucose concentrations in both subgroups differed similarly (p less than 0.02). The magnitude of the insulin increase did not correlate with severity or type of injury but showed a strong dependence on the time elapsed following trauma. Strong hyperinsulinemia appears to be less detrimental to survival than severe hypoinsulinemia manifested with a very low insulin-to-glucose ratio. Since both forms of insulinemia may occur under similar clinical conditions, early routine determinations of serum insulin levels are recommended in order to introduce effective therapeutic measures.


The subcellular pathology of shock in trauma patients: studies using the immediate autopsy.

In summary, our immediate autopsy program provides a new tool for investigating the pathophysiologic effects of shock and trauma at the cellular and subcellular levels. By minimizing the time delay between death and tissue sampling with this technique, we have demonstrated the feasibility of validly applying the refinements of electron microscopy, histochemistry and analytical biochemistry to human tissue. Qualitative, semi-quantitative and quantitative data with these techniques have been integrated with clinical, physiologic and chemical studies on these patients during life. Cell injury produces an altered steady state of metabolism within the cell, evidence of which is seen in altered ultrastructure. If the injury is too severe, the cell will pass the "point-of-no-return," at which time the changes in the cell are no longer compatible with life and the cell dies and undergoes necrosis. Although the initiating injury and the patterns of the altered steady state may vary, once the cell has passed the "point-of-no-return," the patterns of cell injury regardless of the initial insult, are similar. We believe that the cellular patterns seen in patients dying from shock and trauma are remarkably similar to those produced by hypoxic tissue injury in experimental systems. Tissue from control patients in whom ischemic injury due to episodes of hypotension did not occur show good morphologic preservation with normal mitochondria and other cell organelles. Tissue from patients who have experienced acute shock consisting of a period of hypotensive ischemia show changes in the mitochondria and ER compatible with the experimental picture of hypoxia: i.e., dilated ER, with loss of ribosomes, swelling of mitochondria and the appearance of flocculent densities in the mitochondria. Tissues taken from the patients who had experienced repeated episodes of shock, whom we designated as those in "chronic shock," showed changes paralleling the acute changes, but also showed much evidence of autophagocytosis as a) the cells attempted to achieve a lower metabolic requirement in order to survive, and b) they attempted to "clean-up" and remove altered and damaged organelles and debris from previous bouts with sublethal ischemic injury. We hope that the increased knowledge of tissue and cellular injury obtained by the immediate autopsy will provide a means of integration, hypothesis formation and testing of the vast knowledge of cell biology and pathology, and the opportunity for developing in the human the potential for testing new hypotheses in model systems resulting in immediate and innovative feedback for the patient in terms of diagnosis, functional monitoring and treatment.


Cerium nitrate-silver sulfadiazine cream in the treatment of burns: a prospective, randomized study.

In a prospective, randomized study of 34 patients with thermal burns, treatment with the topical agent Cerium nitrate-silver sulfadiazine was compared with therapy with silver sulfadiazine alone. Despite randomization, there was a significant difference in mean burn size, being larger in the silver sulfadiazine group. There was no significant difference between the two groups in clinical course, mortality, septic deaths, or quantitative microbiology of the burn wound. It is concluded that from these preliminary data no clearcut superiority for one cream over the other can be demonstrated at this time.


Clinical aspects of Legionnaires' disease.

Since the initial description of Legionnaires' disease 2 years ago, a clearer picture of its clinical manifestations has emerged as a result of investigations of further epidemics and studies of laboratory-confirmed sporadic cases. Although individual clinical features are not sufficiently distinctive to distinguish Legionnaires' disease from other types of acute pneumonia, a composite can provide a sufficiently characteristic clinical profile to indicate the likelihood of this diagnosis. Such a profile includes high fever (above 39.4 degrees C); recurrent chills; relative bradycardia; early gastrointestinal symptoms (particularly diarrhea); prominent myalgias; microscopic hematuria; liver function abnormalities; toxic encephalopathy; nonproductive cough; absence of bacterial pathogens on Gram stain and culture of transtracheal aspirate; progression from patchy bronchopneumonia to lobar and multilobar consolidation; and frequently prompt and sometimes dramatic response to treatment with erythromycin.


Epidemiology of Legionnaires' disease.

Ten recorded epidemics of Legionnaires' disease are reviewed to gain a working perspective on the epidemiology of the disease. Salient features have included a summer-fall seasonality, a male predominance that may largely reflect increased exposure risk among men, and a striking absence of person-to-person spread. That the disease is spread primarily via the airborne route is well established; air-treatment and air-conditioning equipment has been implicated as the amplification and delivery system in four epidemics. Soils and excavation sites have been suggested as sources of the organism in at least one recorded epidemic. Evidence to date suggests that the Legionnaires' disease bacterium may be widespread in nature. More complete epidemiologic understanding must await development of improved microbiologic and immunologic tests.


Immunology and immunopathology of Legionnaires' disease.

The immune response to the Legionnaires' disease (LD) bacterium has been shown serologically. Recent evidence suggests significant differences in seroreactivity depending on the source of antigen; these data now unequivocally show strain variation for the LD bacterium. Nothing is known about the cellular immune reactivity in patients with Legionnaires' disease. There is little evidence that the lesions and manifestations of the disease are due to immunopathologic mechanisms. Possible explanations for the pathogenesis of pulmonary lesions in Legionnaires' disease include toxic factors, bacterial chemotactic factors, neutral proteases (with complement cleaving activity), lipopolysaccharides, and products of lymphocytes.


Legionnaires' disease: clinical features of the epidemic in Philadelphia.

A review of the medical records of 123 persons with Legionnaires' disease hospitalized in the 1976 Philadelphia epidemic showed that the manifestations of infection ranged from mild grippe to a severe pneumonia that also involved other organ systems. Early in the illness, constitutional symptoms predominated. Fever, malaise, myalgia, rigors, confusion, headache, and diarrhea were usually followed by nonproductive cough and dyspnea. Physical examination showed few abnormalities other than rales. Moderate leukocytosis with left shift, elevated erythrocyte sedimentation rate, elevation of serum levels of liver enzymes, and hematuria and proteinuria were characteristic. Chest radiograph showed patchy, often nodular, areas of consolidation. Progression of pneumonia led to respiratory failure and the need for mechanical ventilatory assistance for 19 patients; renal failure, primarily after shock, occurred in 18 persons. Twenty-six patients died. Treatment with erythromycin or tetracycline resulted in the lowest case-fatality ratios, but the associations were not statistically significant.


Sporadic cases of Legionnaires' disease: the expanding clinical spectrum.

An analysis of seven sporadic cases of Legionnaires' disease confirmed clinical features recorded during epidemics and identified aspects of the illness either unreported or not emphasized. Four patients had central nervous system abnormalities. Mental status changes included somnolence, obtundation, delirium, disorientation, and confusion. Three patients experienced visual hallucinations, and one patient without pneumonia had a grand mal seizure with residual memory deficit. Two patients had disseminated intravascular coagulation with thrombocytopenia, elevated split fibrin products, and prolonged partial thromboplastin and prothrombin times. Four patients had severe hypoxia; one patient had an exudative pleuritis. One patient whose treatment included erythromycin had radiologic improvement of his pneumonia despite deteriorating ventilatory function that led to death. The concept of Legionnaires' disease as a severe, diagnostically perplexing pneumonic illness is valid but too narrow. The emerging spectrum is that of a multisystem disease that, besides the lungs, often involves the central nervous system and can be accompanied by disseminated intravascular coagulation.


Early clinical differentiation between Legionnaires' disease and other sporadic pneumonias.

Early diagnosis of Legionnaires' disease is difficult because other pathogens cause a similar clinical picture and microbiologic tests are usually only of retrospective value. Since May 1977, 17 patients with sporadic cases of Legionnaires' disease have been admitted, all previously well, the diagnosis being made with standard serologic or bacteriologic criteria. From the clinical, laboratory, and radiologic findings, we propose criteria that may enable the clinician to make a diagnosis earlier in many cases, differentiating them from other pneumonias. Within 24 hours of admission, any three of the following four features are strongly suggestive of Legionnaires' disease: [1] prodromal "viral" illness, [2] dry cough or confusion or diarrhoea, [3] lymphopenia without marked neutrophilia, [4] hyponatremia. Two thirds of cases had at least three of these features, and no false-positive diagnoses would have been made in other pneumonias that were serologically negative for Legionnaires' disease if these proposed criteria had been applied diagnostically. In the next few days the diagnosis is very likely if microbiologic tests are negative and if there is radiologic extension, abnormal liver function test results, or hypoalbuminemia.


Sporadic cases of Legionnaires' disease in the Netherlands.

Sera of 24 patients with an unexplained pneumonia were tested for the presence of antibodies against the Legionnaires' disease bacterium. Fifteen patients had positive serology. The series comprised 12 male and three female patients ranging in age from 17 to 66 years (mean, 51.1 years). All of the patients had a high fever, little or no sputum production, and radiographic evidence of pneumonia. The radiographic abnormalities ranged from a patchy infiltrate to extensive consolidation. In eight patients with confirmed Legionnaires' disease, severe confusion was one of the most striking signs. A variety of antibiotics had no clear effect on the duration of the illness in these cases, although the severity seemed to be influenced. Two of the patients died, and in three the course was protracted. All cases were sporadic. Eight patients had been infected abroad and seven in the Netherlands, two of whom were on immunosuppressive therapy and were infected in a hospital.


Comparative features of pneumococcal, mycoplasmal, and Legionnaires' disease pneumonias.

Retrospectively, we clinically compared community-acquired cases of Legionnaires' disease, pneumococcal, and mycoplasmal pneumonias. Relative to pneumococcal and mycoplasmal pneumonias, patients with Legionnaires' disease were significantly more likely to present with unexplained encephalopathy, hematuria, and elevation of serum glutamic-oxalacetic transaminase than were those with pneumococcal and mycoplasmal pneumonias. We found upper respiratory symptoms infrequently in patients with Legionnaires' disease, and progression of pulmonary infiltrates occurred commonly. Differentiation of Legionnaires' disease pneumonia without encephalopathy from pneumococcal and mycoplasmal pneumonias may be difficult because of demographic, clinical, laboratory, and radiographic similarities.


Macroscopic pathology of the lungs in Legionnaires' disease.

We used the whole lung section technique to review the macroscopic pathology in 12 patients who died with Legionnaires' disease. None of these patients had been treated with erythromycin. Consolidation was evenly distributed throughout all lobes without a consistent segmental distribution. The smallest lesions were around bronchioles or bounded by lobular septa. In most cases there was confluent involvement of multiple lobules. Extensive consolidation made distinction between a lobar and confluent lobular distribution difficult. Abscesses were present in two cases and nodular infiltrates in two others. In five additional patients, Legionnaires' disease had been treated with erythromycin. Four had a clinical response to treatment, and the fifth had diffuse staphylococcal pneumonia as the predominant lesion. Because the lungs of all five patients contained bacteria other than the Legionnaires' disease bacterium at the time of autopsy, it was difficult to ascertain the role of Legionnaires' disease bacterium in the pathology.


Pulmonary sequelae of acute Legionnaires' disease pneumonia.

Patients with acute Legionnaires' disease (LD) pneumonia may have persistent chronic pulmonary changes, as shown by the histologic appearance of specimens of lung from patients who had survived and autopsy specimens from patients who died after a protracted clinical course. Acute pneumonia was not seen in these lungs, and LD organisms could not be identified by the direct fluorescent antibody technique or the Dieterle silver impregnation strain; instead, there was organizing pneumonia with various degrees of interstitial inflammation and fibrosis. The LD pneumonia may fail to resolve, and the lung parenchyma in areas of previous acute inflammation is not restored to normal in some patients.


Ultrastructure of lung in Legionnaires' disease. Observations of three biopsies done during the Vermont epidemic.

Open lung biopsies from three patients with Legionnaires' disease were examined by light and transmission electron microscopy. The patients had serious underlying disease. All developed a rapidly progressive pneumonia unresponsive to penicillin, oxacillin, and gentamicin. One patient, who received erythromycin, survived. Light microscopy in all three showed severe acute bronchopneumonia. The Legionnaires' disease bacterium was seen in tissue sections and confirmed by direct immunofluorescence. Transmission electron microscopy showed numerous rod-shaped intracellular organisms that were morphologically similar to other gram-negative bacteria and the Rickettsieae. They were within phagolysosomes, free in the cytoplasm, and rarely within structures resembling dilated rough endoplasmic reticulum. Lung tissue changes included marked detachment and necrosis of alveolar pneumocytes, septal and alveolar exudate with lysis, and prominent endothelial cell swelling and degeneration. Capillary and epithelial basement membranes were consistently intact, suggesting that the tissue changes are potentially capable of reverting to normal structure and function.


Legionnaires' disease and the traveller.

Respiratory illness occurred in members of a "package tour" to Benidorm, Spain, in 1973. Three of the tourists died with similar pneumonic illnesses, and 86 other travellers who had stayed at the same hotel also had respiratory illnesses. After the organism associated with the epidemic of Legionnaires' disease in Philadelphia 3 years later was identified, sera from patients involved with the "Benidorm episode" were tested. Evidence of infection with the Legionnaires' disease bacterium was obtained from sera from three of the patients who had died and from sera of two of the surviving tourists. Six of 16 members of the staff of the hotel involved had elevated titres to the LD bacterium, suggesting that there may be persistent or recurrent activity in a particular building or locality over a period of years. Surveys of travellers returning to Scotland have shown a large amount of illness, and studies are being conducted to determine the proportion caused by Legionnaires' disease.


Legionnaires' disease in Kingport, Tennessee.

In August and September 1977 a discrete cluster of 27 serologically or pathologically confirmed cases of Legionnaires' disease, plus six highly presumptive cases were identified in the area of Kingsport, Tennessee. Three patients died. Most patients manifested severe pneumonia and fever; no mild or asymptomatic disease forms were recognized despite intensive case-finding efforts. Illness was epidemiologically associated with residing, visiting, or working in one geographic area of Kingsport, residence there being the factor most strongly associated. Although the attack rate for area residents was 0.64%, the randomly determined prevalence of serologic reactors was 5.2%, which is not significantly different from that in a nonimplicated control neighborhood. The epidemic did not correlate temporally with any identified environmental or demographic event. No source of the bacterium was found either by a detailed case-control study of area associations or by bacterial isolation from sentinel guinea pigs or environmental specimens. There was no evidence of person-to-person spread.


The Vermont epidemic of Legionnaires' disease.

Sixty-nine laboratory-documented cases of Legionnaires' disease occurred in Vermont between 1 May and 31 December 1977. Clinical manifestations were similar to those in the 1976 Philadelphia epidemic. Case-control studies suggested that Legionnaires' disease patients were more likely to present with headache or diarrhea than were patients with pneumonia of presumed nonbacterial cause. The case-fatality ratio for patients treated with erythromycin was 4%, compared with 17% in patients not treated with erythromycin. Thirteen patients had been hospitalized throughout the 10 days preceding onset of illness, equaling the maximal known incubation period. This suggests either acquisition or reactivation of infection in the hospital. However, even during the week of peak disease activity, cases occurred in patients with no recent hospital contact. The only community factor possibly associated with acquisition was home air conditioning. This prevalence of seroreactivity to the Legionnaires' disease bacterium in various community populations was as high as 26%, suggesting a possible endemic area.


Summertime pneumonias in Philadelphia in 1976. An epidemiologic study.

Summertime pneumonias in Philadelphia during 1976 were studied epidemiologically, and the epidemiologic, clinical, and laboratory features of pneumonia cases serologically positive for Legionnaires' disease were compared with features of serologically negative cases. Both groups were similar in many respects, but in patients with Legionnaires' disease diarrhea and neurologic findings were significantly more frequent (P = 0.01 and P = 0.05 respectively). A diagnosis of Legionnaires' disease was also suggested by an elevated serum creatinine phosphokinase level (P = 0.02) and the presence of occult blood in the urine with fewer than six erythrocytes per highpower field. Abnormalities in renal function tests or liver function tests were commoner in patients with Legionnaires' disease (P = 0.05). Radiographic features, however, could not be used to separate pneumonia cases. The high frequency of extrapulmonary manifestations involving the gastrointestinal tract, the central nervous system, kidneys, and liver suggests that Legionnaires' disease is a multisystemic disorder possibly caused by a toxin-producing organism.


Legionnaires' disease in Nottingham, England.

Legionnaires' disease bacterium was identified as the cause of severe pneumonia in some Nottingham, England, patients in 1977. Laboratory studies were not restricted to Nottingham but included several other areas in England. The 41 cases identified were evenly divided between areas; they also accounted for about one half of all cases for the entire country. No source of infection has been identified in these sporadic cases. There was no contact between patients, and only a few had travelled abroad before their illnesses. Serologic sampling of populations in Nottingham did not reveal a large background of infection. Only 31 of 2023 sera tested had low titer antibody to the Pontiac antigen used. Guinea-pig antisera to two positive lung extracts showed an antigenic relation to the Pontiac but not to the Togus strain,suggesting strain variation.


A major focus of Legionnaires' disease in Bloomington, Indiana.

Thirty-nine cases of Legionnaires' disease in a 16-month period were identified in visitors to and residents of Bloomington, Indiana. Thirty-five patients had spent at least one night at the Indiana Memorial Union in the 2 weeks before becoming ill. Five of 32 sporadic cases nationwide between 1 January and 31 March 1978 were retrospectively shown to be in persons who had recently visited the Union. The risk of acquiring Legionnaires' disease as a Union visitor was at least 17 times greater than that for Bloomington residents 20 years or older. Employees who had worked at the Union 5 years or longer were more likely to be seropositive than workers in other Bloomington hotels. Legionnaires' disease bacterium was isolated from five environmental sites in Bloomington. A cooling tower may have been involved in disease spread, but it was not the only source. Hypochlorite solution was added to cooling tower water as a precautionary measure; however, one case was confirmed in a man with Union exposure 9 days after hypochlorite treatment had begun.


Sporadic cases of Legionnaires' disease in Great Britain.

Data on sporadic cases of Legionnaires' disease in Great Britain reported to the Communicable Disease Surveillance Centre, London, and the Communicable Diseases (Scotland) Unit, Glasgow, were analysed. Eighty-four cases, including 18 patients who died, were identified with dates of onset between 1 January 1976 and 30 September 1978. The age and sex distribution showed a predominance of middle-aged men. The incidence trends suggest that true seasonal variation may occur. Eighteen patients developed illness during or shortly after a holiday abroad. All patients had pneumonia, but many also had features suggesting involvement of the central nervous system and gastrointestinal tract. Person-to-person spread was not observed.