On the metabolic characteristic of hybrids Shigella flexneri x Escherichia coli devoid of their ability for intracellular multiplication in the epithelial cells. I. Glycolysis. The glycolysis (aerobic and in the presence of KCN) of avirulent xyl+ and xyl-str hybrids Sh. flexneri x E. coli, devoid of their ability to multiply intracellularly in the epithelial cells, is studied. It is established that their glycolytic activity is considerably higher than the activity of the donor strain E. coli, and deviate significantly compared with shown activity of the virulent recipient strains Sh. flexneri. Xyl-str hybrids are showing high values of glycolysis in aerobic conditions and in the presence of KCN, while in xyl+ hybrids very active glycolysis is observed only in the presence of KCN - probably completely sufficient for the persistence of bacteria in the host-cell at anaerobic conditions.


On the metabolic characteristic of hybrids Shigella flexneri x Escherichia coli devoid of their ability for intracellular multiplication in the epithelial cells. II. Catalase and phosphatase activity. The catalase and phosphatase activity of avirulent by keratoconjunctival test of guinea pigs xyl+ and xyl-str (KCP-) hybrids that have lost their ability for intracellular multiplication, received from virulent strains. Sh. flexneri (Sh. flexneri 222 5 a and Sh. flexneri M42-43) and donor strain E. coli AB 313 was investigated. It is established that there is a definite dependence between the changes in the catalase and the phosphatase activities of the hybrid strains and the newly received by the hybridization genetic information. The enzyme activity of the hybrid strains always correlated with the level of this activity in the donor strains E. coli.


[Comparative studies with the rapid KCN-test for Enterobacteriaceae according to Cahan, Sechter and Ohad (author's transl)]. 581 strains of Enterobacteriaceae (184 of Salmonella, 100 of Shigella, 31 of Citrobacter freundii, 61 of Escherichia coli, 40 of Klebsiella, 165 of Proteus) were investigated in comparison with the KCN-test according to Møller and with the rapid KCN-test according to Cahan, Sechter and Ohad. There was found that the results obtained with both methods were identical to 99 percent. In both tests there could be observed that inexplicable differences occur only in two strains of Proteus mirabilis. The rapid KCN-test can be recommended because of the good durability of the basic medium and of the solutions of the reagents, because of the short testing time (3 h), of the very good correspondence of the results and of the possibility of a well defined reading.


Inositol as a selective substrate for the growth of Klebsiellae and Serratiae. A synthetic basal salts medium containing inositol as the sole source for carbon and energy and bromothymol blue as pH indicator, selectively supports the growth of Klebsiella pneumoniae and Serratia spp. On this medium incubated at 37 degrees C for 24 hr, all cultures of Kl. pneumoniae, Serratia liquefaciens and S. marcescens form yellow colonies. The medium may be used selectively for the primary isolation of the aforementioned bacteria from faeces and as a differential medium for their isolation from saliva and urine.


Survival of T. pallidum under microaerobic conditions in cell and tissue cultures. The survival of pathogenic T. pallidum was studied under microaerobic conditions (partial pressure of oxygen 7 mm Hg) with and without tissue cell cultures. As between one third and half of the germs were motile even after 96 hours of incubation, treponemes do not seem to be strictly anerobic as has been generally believed so far. Flocks containing enormous numbers of treponemes were observed in the nutrient medium. For their formation, human serum, testicular components from rabbits and modified Nelson's survival medium were essential. Although the problem of cultivation of T. pallidum remains to be solved the formation of flocks indicates a possible transient multiplication of treponemes in vitro.


[Phagocytosis and intracellular proliferation of Nocardia asteroides (strain Weipheld) in cell structures in vitro. 2. Peritoneal macrophages of guinea-pigs (author's transl)]. The study deals with the phagocytosis of Nocardia asteroides (strain Weipheld) and the subsequent intracellular proliferation in peritoneal macrophage cells. Normal, two-stage-immunized and long-term cortison-treated guinea-pig (28 mg cortison / kg weight / day during 30 days) macrophages were used. Further, the cytotoxic effect of Nocardia upon the cells in the peritoneal washing liquid in vitro and the influence of the normal, immune and antimacrophage serum upon the phagocytosis and the intracellular proliferation were studied. Among the cells obtained from the peritoneal washing liquid macrophages were most frequently subject to phagocytosis, leukocytes to a lesser degree. The normal macrophages phagocytized in 14.56% (Fig. 1), macrophages of two-stage-immunized guinea-pigs in 18.21% (Fig. 2) and macrophages from cortison treated guinea-pigs in 12.48% of cases. Intracellular observation showed phagocytized germs after 3 min. of exposure. The course of the intracellular proliferation of Nocardia can be seen in Fig. 3. The phagocytosis index increases slowly in all three groups of macrophages; least so in the immunized macrophages (1.30-after 8 hours). The highest values were obtained in the macrophages of cortison treated guinea-pigs (2.02-after 8 hours). Within 8 hours of exposure the filaments of Nocardia grew through the cell membrane of phagocytizing cells (Figs. 4 A, 4 B). Fig. 5 shows the course of the cytopathogenic effect of Nocardia upon the cells. After 1 hr. the number of dead cells increased from 0.30% to 1.9-3.8%; after 4 hrs. it reached 8.15-9.80%; after 8 hrs. 10.1-14.80%. The highest values were observed in cells from cortison treated guinea-pigs (14.80%). After addition of normal serum (time of phagocytosis 60 min.) normal peritoneal macrophages phagocytized in 13.30% of cases; immune serum stimulated phagocytosis (16.21%); antimacrophage serum significantly reduced phagocytosis (4.10%). The phagocytosis index in peritoneal macrophages with normal and immune serum increased, reaching values of 1.20-1.58 with in 8 hours; the differences were statistically not significant (Fig. 6). A significant increase of proliferation was observed in peritoneal macrophages with antimacrophage serum (2.07 in 8 hours). Neither normal nor immune guine-pig serum influenced the cytopathogenic effect of Nocardia on the cells of peritoneal washing liquid (Fig. 7). The antimacrophage serum had a rapid and expressive effect upon the macrophages (78.23% of cells died after 2 hours, 100% after 3 hours of exposure).


[Viable bacterial counts by agar-droplet technique (author's transl)]. This paper deals with 1) Analysis of the agar droplet technique for viable bacterial counts with respect to a new technical aid (Colworth DROPLETTETM); 2) Comparison of the results obtained from two conventional plate count techniques and the agar-droplet method; 3) Examples for the practical use of this new technique. As a helpful aid for the agar-droplet technique there now exists an apparatus (Colworth DROPLETTETM, Fig.1) which facilitates dilution and dispension of bacteria containing agar, as well as counting of colonies grown in agar droplets. Precision and reproducibility of the diluter/dispenser was found to be within the limits of the usual sampling error (Tab.1, Fig. 2, Fig. 3). The visibility of colonies grown in agar droplets is improved by a ten-fold enlargement on the ground glass screen of the viewer (Fig. 7). In order to obtain droplets of equal size a standardised dropping-technique is required. The fluid agar must not exceed a constant temperature of 50 degrees C as otherwise four of the five species tested (Staph. aureus, E. coli, Kl. aerogenes, Ps. aeruginosa and Enterococci) were significantly reduced in number during the manipulation (Fig. 4, Fig. 5). Agar droplet technique, flooding technique and pour plates gave similar results with gram-positive and gram-negative bacteria from medical routine materials. Comparing the arithmetic means, viable counts of Staph. aureus were slightly higher from pour plates while E. coli and Kl. aerogenes gave the highest counts on flooded plates (Tab. 8-11). All of the three methods produced relatively too low counts when the number of bacteria per sample surmounted 300. Counts below 10 allow only a very poor estimation of the actual number of bacteria (Tab. 12). The variability of droplet counts with bacterial numbers higher than 25 was less then the one of corresponding plate counts (Tab. 14-16). Significant savings in materials, labour and incubator space are made with the agar droplet method. As examples for the practical use of the new method the results of the kinetics of thermally inactivated as well as of growing bacteria are presented.


Indirect immunofluorescence in toxoplasmosis: frequency, nature and specificity of polar staining. In the indirect immunofluorescence test ant the Remington test for Toxoplasmosis of some sera, a polar fluorescence of the parasite has been observed. This "Polar Factor" is not observed in umbilical cord blood and in sera of children less than 6 months old, but has a relative high frequency in sera of adults. The detection of the factor depends on the nature of the used antigen. With sucrose gradient centrifugation, anti-IgM immunofluorescence, 2-mercaptoethanol-treatment and selective adsorption of sera, we could demonstrate that this factor is a non-specific IgM.


[Assaying the Enterobacteriaceae contents of fishmeal as criterion for absence of Salmonellae (author's transl)]. 1. During comparison of different test systems for examination on salmonellae the routine method revealed only 2 of 35 fishmeal consignments as positive. In second streaks after 48 hours on selective media 5 more consignments were discovered to contain samonellae. Using pre-enrichment culture gave evidence for 11 positive consignments altogether. 2. The pre-enrichment method led to about 20 times higher yields in isolating enterobacteriaceae than the usual enrichment method. 3. Neither salmonellae nor enterobacteriaceae statistically showed uniform distribution in fishmeal. In addition, with the aid of the variance test of homogenity, an extremely heterogeneous ratio of the both germ types to each other was proved. Consequently, assaying the enterobacteriaceae contents is not suitable to draw any reliable conclusions upon the salmonellae contents of fishmeal. 4. Assuming a constant contamination rate of 400.000 salmonella units in consignments of 100 tons and testing them by the required 47 random samples, it can be deduced from probability calculus that only about 1 per cent of a larger number of consignments will fail to be recognized as positive. This risk of acceptance increases progressively with diminishing rate of salmonella contamination. Thus about 80 per cent of consignments containing even as much as 20.000 salmonella units will be accepted as "false negatives". 5. Because of the usually low contamination rates of fishmeal it is an erroneous idea to increase the efficiency of assay by modifying the sample sizes in relation to the shipping weight. For this reason the orders for fishmeal examination in the Federal Republic of Germany should be revised. It is suggested to take at least the number of samples required hitherto for consignments of 100 tons. By this without doubt the risk of accepting "false negatives" can be reduced significantly, but it remains still impossible to recognite every contaminated fishmeal consignment and to stop its acceptance by bacteriological examination. 6. From practical examinations and theoretical considerations it is derivable that one has either to tolerate a low degree of salmonella contamination which hygienically may be without any importance or to treat every imported fishmeal by irradiation or heat pelleting.


Salmonella in effluent from sewage treatment plants, wastepipe of butcher's shops and surface water in Walcheren. In the frame of the "Walcheren-project" in which the epidemiology of salmonellosis is studied in a certain area, effluent from sewage treatment plants, wastepipe's of butcher's shops and surface waters, which receive the effluent were studied for the presence of salmonellae. From 160 samples of effluent 150 (94%) contained salmonellae. The most common serotype was S. typhi murium (35%) followed by S. panama and S. infantis. 14 butcher's shops' wastepipes were sampled 54 times. 14 (26%) times salmonellae were found, but only twice was the type isolated from the butcher's shop the same as found in the effluent on the same day. With regard to the presence of salmonellae in surface waters receiving effluent it was shown that from the immediate vicinity of the plant to 250 m downstream from the site of drainage of effluent the number of salmonellae per 100 ml remains almost constant. After 1.5-4 kilometers Salmonella could not be isolated from any of the samples examined. The results underline the hypothesis that salmonellae multiply in the sewage system and/or plant. The spread of samonellae by effluent seems to be limited to the plant itself and of the nearest vicinity. Proposals are brought forward to interupt contamination cycles by decontamination measures.


[Proposal for the introduction of microbial test material in compost windrows for field test (author's transl)]. The introduction and taking of microbial test material for field tests in compost windrows for e.g. the determination of the death rates of patogenic microbes cause various problems in practical use whereby the results of such investigations may be influenced. A device is suggested which allows unlimited microbes taking with the greatest reservation of the windrows and guarantees that during the experiment the introduced microbial test material is actually exposed to the same influences as its neighbouring windrow parts. Comparisons with other methods used are being made.


[Problems of maintaining of hygienic and microbiological quality standards of foodstuffs, particularly of vegetable origin (author's transl)]. As more and more components of our food are nowadays subjected to industrial processing, microbiological controls of raw materials and plant hygiene are important factors in protecting the consumer. In many cases preventive measures and specifications of microbiological characteristics of certain foodstuffs governed by legal regulations do not suffice to guarantee protection of the consumer as desired. For this reason conscientious food manufacturers maintain controls in line with self-imposed and very strict hygienic and microbiological rules. Insufficiencies of the relevant dietetic regulations are exposed and measures to ensure quality recommended. It is shown that, to determine the hygienic and microbiological condition of dehydrated vegetable raw materials, the conditions applying to fresh vegetables must be taken into consideration. Peculiarities pertaining to the microbiological examination of seasonings and methodical problems of determining and judging the spore contents in foods are described.


[L-forms of streptococcus in the scanning electron microscope. 1. Structural elements of L-colonies]. Broth culture of stable L-forms of beta-hemolytic streptococcus, group A, was studied in the log phase. Internal portion of the centrifugate constituting the matrix of the L-population represented a structureless mass in which the borders of individual cells were not always distinct; the cells adhered to one another and were irregular in shape. The described morphological picture corresponded to the internal part of the L-colonies from the semifluid medium in observation under phase and scanning microscope. A more peripheral portion of the centrifugate was formed by the spherical cells, about 2 mum in diameter; penetrating holes or crater-like invaginates and also small spherical structures, about 0.5 mum in diameter were often revealed on these cells. Filamentous structures, up to 200 mum in length which protruded far into the surrounding environment served as the most peripheral elements. Analogous structure were described in the L-colonies examined by phase contrast microscopy. The data of transmission and scanning microscopy are compared.


[Phagocytosis of enteropathogenic escherichiae of serogroup 0124:K72(B17)]. Experiments with phagocytosis of E. coli O124 in the macrophage tissue culture demonstrated a different phagocytability of the S- and R-forms of these bacteria determined by their concentration in the medium. The ingestive and digestive capacity depended on the bacterial virulence. Since R-forms of E. coli O124 lost their virulent properties and macrophage resistance it can be considered that the structure of their lipopolysaccharides served as the chemical substrate responsible for their different phagocytability.


[Distribution of carotenoids in the tissues of high altitude rodents]. Carotenoid distribution has been investigated in the organs of the ground squirrels Citellus suslicus and C. pygmaeus, as well as of the vole Microtus majori inhabiting high mountain regions. It was shown that with the increase of the altitude of habitat the level of carotenoids in the brain and liver increases in the ground squirrels, whereas the vole exhibits the increase of carotenoid content in the spleen, lungs and heart. It is suggested that carotenoids are involved in the intracellular accumulation of oxygen and the increase of their level is associated with adaptation of animals to hypoxic conditions.


On the metabolic radioprotection.

On the metabolic radioprotection. The effect of different factors (0.025 mol/l of cysteine, 0.0003 mol/l of iodoacetamide, 0.328 mol/l of hydroxyurea, deprivation of glucose or essential amino acid and uracil from the medium) on the resistance to gamma rays was studied in the cells of E. coli TAU- during the logarithmic phase. The resistance to gamma rays was also investigated during the stationary phase. It was established that treatments, including reversible inhibition of cell division and unbalance of macromolecular synthesis of a type in which the DNA synthesis was continued without a simultaneous RNA- and protein synthesis enhanced the radioresistance. This type of asynchrony of macromolecular synthesis could increase radioresistance by promotion of repair processes of single-strand breaks in DNA after a single dose of 15 krads irradiation. For this latter studies E. coli K12 (AB 2497) strain and the technique developed by McGrath and Williams was used.


[The significance of stress intensity for the emotional and visceral reactivity, especially for blood pressure regulation]. The influence of light, medium, and heavy chronic stress upon cerebro-visceral functions following 3 and 5 weeks of daily stress exposure was examined. The following results were obtained: Light stress produced no changes of cerebro-visceral functions. Medium stress restricted the learning and memory capacity, increased systolic blood pressure, fasting blood sugar and adrenal weights. The B-cells of the pancreatic islets showed degranulations of varying intensity. Heavy stress diminished the learning and memory capacity, increased adrenal weights and led to hypergranulation of the pancreatic B-cells. Blood sugar and blood pressure values fall within physiological limits. Load tests, however, revealed in these animals symptoms of premorbid states. Since throughout the period of observation, light stress stablized the regulation processes, medium stress induced early stages of pathological processes, and heavy stress caused premorbid states, no linearity could be established between the load intensity and the changes of cerebro-visceral functions.


[Correlations between hippocampus function and stressed learning and their effect on cerebro-visceral regulation processes]. 43 male albino rats were investigated to find out what are the effects of bilateral exclusion of pes hippocampus structures upon the development of arterial hypertension released by learning stress exposure. The following results were obtained: 5 weeks of stress exposure (learning load and heavy learning load) caused disturbances of information-processing events of the central nervous system in all the animals with hippocampal lesions. Systolic blood pressure values, fasting blood sugar values, and adrenal weights fall within the physiological range. The B-cells of the pancreatic islets show hypergranulation. Functional tests of the blood pressure under exercise load, and of blood sugar under glucose load revealed normal reactions in animals with hippocampal lesions. In animals with intact brains the same stress exposure caused pathologic malfunctioning (under learning stress) or even premorbid states. The results being considered in relation to the pathogenesis of arterial hypertension show that the exclusion of circumscribed areas of the hippocampus prevents the development of permanent, stress-induced emotional excitations spreading into the viscerum.


Clinical trials in surgery.

Clinical trials in surgery. Scientific knowledge is reliable because it has been built on accurate measurements. Clinical knowledge is not. The science of biometry was started in 1835 by the Belgian astronomer Adolphe Quetelet. In the last fifty years a precise set of rules have been invented for this science. The method is suitable for a wide range of problems in clinical medicine and as the result of its application in recent years a firm foundation has been laid upon which scientific clinical knowledge can be built. Surge-ns, particularly, have been slow to apply biometrical methods to their clinical problems; but a start has now been made. The outcome of a particular type of treatment is determined by a complex set of inter-acting factors. The basis of the appropriate biometrical method is the elimination of all bias in favour of one of the rival techniques being compared. If this precaution is taken the observed results of the trial can be fitted onto Quetelet's distribution graph, and the probability of the observed difference in the results being due to chance, and nothing else, can be measured mathematically. The accuracy of this measurement deteriorates the greater are the number of the patients who can not be found and examined at the end of the trial. To make this point two trials conducted by the author are used. In the trial designed to discover if postoperative deep vein thrombosis and pulmonary embolism could be prevented by electrically stimulating the patients legs during the operation there was no difficulty. All the patients were examined at the end of the trial, because it ended before any of the patients left the hospital. The trial to discover if the primary treatment of varicose veins ought to be by Fegan's sclerotherapy or by operation was the exact opposite. At the end of the first year of the two year trial 15% of the patients could not be traced. The results in these patients, therefore, was unknown. Because of this, elaborate mathematical calculations had to be made to try and reach a reliable conclusion to the trial. The loss of patients before the end of the trial is a very serious practical difficulty which besets all long-term clinical trials.


The use of controlled clinical trials in gastric surgery. Evaluation of results of different surgical treatment of duodenal ulcer requires controlled clinical trials. Some of the published trials have flaws in conception and realization: heterogeneity of material, absence of randomization, incomplete follow-up and incomplete data in results. The author presents a controlled clinical trial, following a carefully planned protocol, comparing results of gastric proximal vagotomy without drainage to those of selective vagotomy with gastro-jejunostromy. This study has shown the mean term advantages of proximal gastric vagotomy without drainage, and of the controlled clinical trial in demonstrating the pros-and-cons of a gastric operation for a duodenal ulcer.


Tissue holding power to a single suture in different parts of the alimentary tract. Figures for tissue strength are reported from an investigation on the tissue holding power to a single suture in 8 parts of the gut between oesophagus and rectum in 71 preparations from 44 individuals. 1749 experiments were done. Three layers were tested in each part of the gut. The mean holding power of sutures in the mucosa was 0.26-0.83 kp, for those in the seromuscular coat 1.03-2.24 kp, and for through-and-through sutures, 1.02-2.54 kp. Appreciable differences in tissue strength appear to exist between different parts of the alimentary tract. The lowest values were noted in the oesophagus and sigmoid, and the highest in the stomach and colon. Sutures through the whole gut wall were hardly any stronger than sutures in the sero-muscular coat. There was a significant difference in holding power in cancer compared with non-cancer cases. The holding power was considerably reduced in subjects with cancer in the alimentary tract. Knowledge of tissue strength in the gut may help to explain why anastomoses break down, and will provide a firmer basis for the choice of sufficiently strong suture material and knots with a view to preventing this complication.


Tissue strength of structures involved in musculo-aponeurotic layer sutures in laparotomy incisions. Tissue strength to breaking point against the pulling forces of a suture was investigated in the musculo-aponeurotic layer of the six laparotomy incisions most commonly used in surgery, namely 1) mid-line incision, 2) paramedial incision, 3) pararectal incision, 4) transverse incision, 5) right oblique subcostal incision, and 6) McBurney's incision. When the suture length was 5 mm and the interval between sutures 10 mm, the mean tissue holding power was 1.9 kp for peritoneum and transversalis fascia together; 5.6 and 3.2 kp for longitudinal incisions through andinary sutures; and 22.9 kp for linea alba with sutures placed lateral to the transition between linea alba and rectus sheath. In comparison with these longitudinal incisions the tissue-holding power in corresponding tissues in transverse incisions was greater (c. 40% greater in the linea alba and anterior rectus sheath and c. 60% greater in the posterior rectus sheath). When regard was paid to the total closure strength of the musculo-aponeurotic layer, e.g. in paramedian incisions the sum of the figures for the anterior and posterior rectal sheaths, the paramedian incision was found to give the weakest closure, followed by the only slightly stronger pararectal incision. The strongest closure was obtained with the midline incision through the linea alba when the  sutures were placed laterally to the transition between the linea alba and the rectus sheath. The values for holding power recorded for the musculo-aponeurotic layer may provide a rational basis for the choice of thread dimension and knot type in order to create a suture loop that will be at least as strong as the tissue.


Serum LH and FSH levels following intravenous injection of a gonadotrophin releasing principle in normal and gonadectomized adult male rats treated with oestradiol-17beta or 5alpha-dihydrotestosterone. Effect of intravenous administration of a synthetic gonadotrophin releasing factor (GnRF) on circulating LH and FSH concentrations was investigated in normal and gonadectomized, adult male rats injected subcutaneously each day during seven days with various doses of oestradiol-17beta or 5alpha-dihydrotestosterone in sesame oil. Higher increase in serum LH and FSH levels subsequent to intravenously administered GnRF was observed in castrated control animals than in intact control animals, though this increment was not of significant nature for serum FSH. Pre-treatment of normal and gonadectomized rats with oestradiol-17beta resulted in an augmented response of serum LH and FSH concentrations to GnRF iv. Pre-treatment of normal and gonadectomized rats with 5alpha-dihydrotestosterone diminished serum LH and FSH response following administration of the same amount of GnRF. For these steroids to affect the response pattern of serum LH and FSH to GnRF iv, higher doses were required in normal than in gonadectomized animals. The data indicate that oestrogen and androgen may act at different sites in the male hypothalamic-pituitary axis with respect to regulation of pituitary gonadotrophins.


Etidocaine in retrobulbar anaesthesia. A comparison with mepivacaine. A new long-acting local anaesthetic, etidocaine (Duranest) has been compared to mepivacaine (Carbocaine) in retrobulbar anaesthesia in a double-blind trial including 45 patients. Solutions used were etidocaine 0.5% and 1% and mepivacaine 1%, all without adrenaline. The onset time was short and no difference was found between the solutions. The duration of analgesia and motor block was significantly longer with etidocaine 1% compared to mepivacaine 1%. In a following open study with etidocaine 1% and mepivacaine 1% about 80% of the the patients in the etidocaine group never experienced any post-operative pain compared to about 50% in the mepivacaine group. No signs of local or systemic toxicity were noted in the studies.


Exfoliative cytology in the diagnosis of immunologic rejection in the transplanted kidney. Urinary cytology was used in the study of 57 patients who received renal allografts. In general, there was close correlation between the cytologic and clinical evidence of rejection and, at least in some instances, rejection was detected cytologically prior to the onset of clinical signs and symptoms. A cytologic profile associated with rejection was established. This had as its main feature an increased number of tubular cells, particularly those that were small and degenerating. An associated background of cellular debris and casts was found to be of major significance. Intranuclear inclusions suggestive of viral infections were present in 15 patients. Cellular atypias caused by factors other than immunologic rejection were seen but none were of a malignant nature. It was considered of importance that the method described in this study could be carried out in a routine diagnostic cytopathology laboratory by cytotechnologists and cytopathologists who had received only a brief period of special training in the field of transplant cytology.


Human auto-immune thyroiditis.

Human auto-immune thyroiditis. Focal or diffuse infiltration of lymphoid cells in auto-immune thyroiditis destroys the parenchyma. In the diffuse form (Hashimoto's disease), the clinical picture is characterized by fatigue and thyroid enlargement. The diagnosis is settled by cytology. All patients must be treated with thyroid hormones to avoid myxoedema. Loss of immunological tolerance and cytotoxic immune reactions is discussed.


Long-term treatment of nasal polyps with beclomethasone dipropionate aerosol. I. Treatment and rationale. Beclomethasone dipropionate is a potent corticosteroid, which when applied by a pressurized metered dose aerosol in the airways has pronounced anti-allergic effects with no risk of systemic steroid side effects at the recommended dosage. An impressive effect in hay fever and perennial rhinitis has been demonstrated. A double-blind short-term trial showed that the drug was effective in about 80% of patients suffering from moderate to severe nasal polyposis. A study of the long-term effects on the nasal mucosa is indicated.


Long-term treatment of nasal polyps with beclomethasone dipropionate aerosol. II. Clinical results. The effect of a one-year treatment with intranasal beclomethasone dipropionate in 33 patients with long-standing nasal polyps was determined. About 80% of the patients obtained good or excellent relief of symptoms. No adverse reactions of any importance occurred. It is suggested that intranasal beclomethasone dipropionate is close to the ideal basic treatment for patients with nasal polyps.


Spontaneous portorenal shunting in portal hypertension assessed by a dye dilution technique. Using a dye dilution technique, blood flow was measured in the right and left renal veins in 12 patients with portal hypertension. There was evidence of spontaneous shunts to the left renal vein in all cases and at least in 4 cases to the right one. Spontaneous portal systemic shunts other than via esophageal varices is probably much higher than hitherto known.


[Long-term treatment of nasal polyps with beclomethasone dipropionate aerosol. III. Morphological studies and conclusions]. Morphological studies during the treatment of patients with nasal polyps with beclomethasone dipropionate aerosol for one year showed a trend towards a decrease in the number of eosinophils in nasal smears and falls in the increased concentrations of albumin, IgG and IgE in the nasal secretion. No change in the histological picture of the polypous tissue except increased density was observed. By scanning electron microscopy, no change in the surface structure of the nasal mucous membrane was noted. As morphological studies did not reveal any sign of adverse effects, beclomethasone dipropionate may be regarded as a valuable drug in the treatment of nasal polyps. The indications for its clinical use and supplementary therapy are discussed.


Lithium treatment of meniere's disease. Results of a double-blind cross-over trial. 21 patients with Meniere's disease participated in a double-blind, cross-over trial, with 6 months' lithium treatment and 6 months' placebo treatment. Even if the results were not completely unequivocal, no difference was found between lithium and placebo treatment. The results might imply that both other medical as well as surgical treatment of Meniere's disease exert a pure placebo effect; so far no controlled investigation has been published, establishing the value of surgical treatment of Meniere's disease.


Hyoscine-N-butylbromide (Buscopan) as a duodenal relaxant in tubeless duodenography. The efficacy of Buscopan in tubeless duodenography was tested in 48 patients using different routes of administration. The drug led to successful results in 77 to 85 per cent of patients in the dosage used (40 mg), the intravenous route proving the most efficient. The drug is considered superior to Probanthine and glucagon (Glucagon-Lilly) in view of its safety, low incidence of side-effects and efficacy. Follow-through examinations of the small bowel at 1 hour are possible in 33 per cent of patients, although 40 per cent have mild residual abnormalities only.


Immunoglobulins and complement in chronic myocardial disease. A myocardial biopsy study. Autoimmune mechanisms have been suggested to be of significance in chronic myocardial diseases. However, the frequency and importance of these factors are unknown. In the present study, endomyocardial biopsy specimens from 21 patients with chronic myocardial disease have been examined by direct immunofluorescence for the presence of immunoglobulins and complement factor C3. Positive staining for immunoglobulin and/or complement was observed in 7 cases. None of the specimens stained for albumin or amyloid. The immunoglobulin deposits were located on the surface of the myofibre and in all but one case, complement was found in the same location. The presence of the complement together with immunoglobulin, and also the lack of albumin, may suggest an immune reaction and not just a passive deposition secondary to heart muscle damage. The localization along the fibres further suggests that the deposits represent an autoimmune reaction to antigens on the fibres and not a trapping of circulating antigen-antibody complexes. It is not known whether the deposits are primary or secondary events, but they may be of importance in initiating or maintaining derangement in heart function.


Sports and longevity.

Sports and longevity. The mortality of 396 Finnish champion skiers born from 1845 to 1910 was followed up to the end of 1967. Their median life expectancy was 73.0 years, ie.e 4.3 years longer than that for the Finnish male population during the same period. Former skiers have low blood pressure, seldom smoke and are physically active. Increased longevity has been reported also for American college oarsmen and baseball players.


Laboratory and clinical evaluation of a new synthetic absorbable suture for ophthalmic surgery. A new synthetic absorbable suture, a copolymer of two simple hydroxy acids, glycolic acid and lactic acid, was evaluated in a laboratory and clinical study for its usefulness in ophthalmic surgery. The glycolactide was compared with chromic collagen of similar size. The 8/0 glycolactide showed 30% greater initial strength than 8/0 chromic collagen. Following implantation of the suture in rabbit corneas, the suture was removed at intervals and its rupture strength tested. At the end of 1 week the glycolactide retined over 90% of its initial rupture strength while chromic collagen had lost nearly 50% of its strength. After 10 days the strength of the glycolactide tended to fall rapidly and by day 21 the suture had negligible strength and began to absorb, completely disappearing by 7 weeks. Chromic collagen tended to remain in situ for many weeks although possessing negligible rupture strength. The 8/0 glycolactide was compared with 8/0 chromic collagen in suturing corneoscleral wounds of 45 consecutive patients undergoing routine cataract surgery. Handling qualities were judged and the eyes followed post-operatively to ascertain reaction to the sutures and time of final disappearance of the sutures from the eyes. The glycolactide showed no tendency to disappear from the wounds until after the fourth week. By the end of 9 weeks all the glycolactide sutures had disappeared. Chromic collagen, on the other hand, was more variable, some sutures disappearing as early as the third week while others remained in place essentially unchanged for more than 20 weeks. Neither glycolactide nor chromic collagen showed any tendency to excite reaction in the eyes and the incidence of complications was low.


Absorption time of PGA monofilaments and collagen 8/0 in corneal sutures. Absorbable corneal sutures of PGA monofilaments were tested in rabbit eyes. Compared to chromic collagen 8/0 the sutures were tolerated well, but the absorption time of 14.6 days is considered as being too short for corneal surgery.


Effects of some naturally occurring prostaglandins and synthetic analogues on gastric secretion and ulcer healing in man. The effects of several naturally occurring prostaglandins and their synthetic analogues on gastric acid secretion in man have been studied. Naturally occurring prostaglandins when given orally do not inhibit gastric secretion in man with the exceptions of PGA2, PGB1, and PGB2. The effect of PGB compounds in inhibiting gastric secretion is inconsistent and unpredictable, whereas PGA2 produces only a transient inhibition of acid secretion. Several synthetic analogues of prostaglandin E2 (particularly 15-methyl and 16,16-dimethyl analogues) produce a marked and sustained inhibition of acid secretion in man when administered orally. In a double-blind study 15(R)-15 methyl-PGE2 has been shown to be highly effective in healing of gastric ulcers in man possibly by inhibiting gastric acid and pepsin secretion and stimulating mucus production. Prostaglandin E2 (although without effect on gastric acid secretion in man) is also effective in healing of gastric ulcers. Deficiency of prostaglandins as a possible cause of gastrointestinal ulcers is discussed.


Interactions between the renal prostaglandins and the renin--angiotensin system. Although the PGs operate mainly in the renal medulla the demonstration of PG biosynthesis in the renal cortex has provided a biochemical basis for a direct relationship between the PGs and the renin-angiotensin system. The formation of PGs is influenced by circulating levels of A I probably by indirect mechanisms. That the release of renin at least under certain experimental conditions is dependent on the PG system is suggested by the following findings: 1. C20:4 increases PRA in the rabbit and rat. 2. Indomethacin decreases PRA in the rabbit. 3. C20:4 stimulates renin release from slices of rabbit kidney cortex. 4. Reduced renal perfusion pressure and ischemia are accompanied by release of both PGs and renin. 5. The release of PG and renin following renal ischemia is blocked by treatment with indomethacin. The actions of the renin-angiotensin system and the renal PGs are, as far as we know them, antagonistic to each other. PGEs are vasodilator, increase renal blood flow, inhibit adrenergic neurotransmission, and cause excretion of electrolytes and water. Conversely, A II is vasoconstrictor, decreases renal blood flow, stimulates adrenergic neurotransmission, and conserves water and electrolytes. Thus, the interaction between the renal PGs and renin seems to be one in which the two hormonal systems stimulate each other's formation or release, but opposes each other's actions. Further studies are necessary to reconcile this apparent contradiction.


Prostaglandin F2alpha production by the brain and its role in LH secretion. The arteriovenous difference in the concentration of prostaglandin F2alpha (PGF2alpha) across the brain of the anestrous sheep was measured before and during the induction of luteinizing hormone (LH) secretion with estradiol-17beta (E2-17beta). The results indicate that (a) the brain is a significant source of PGF2alpha, (b) the release of PGF2alpha from the brain occurs in pulses with a circhoral rhythm, and (c) the process through which estrogen exerts its negative and positive feedback effects on LH secretion may depend upon amplitude modulation of PGF2alpha output from the brain.


Prostaglandins as mediators of inflammation. 1. Nonsteroid antiinflammatory drugs inhibit prostaglandin biosynthesis in concentrations likely to be found in body fluids during therapy. The assembled evidence, together with the actions of prostaglandins, overwhelmingly supports the theory that this antienzyme effect is the mechanism of action of aspirin-like drugs. 2. Intermediates in prostaglandin biosynthesis and their nonprostaglandin derivatives such as RCS (thromboxane A2) may also play a part in the inflammatory process. 3. There is a close interplay between bradykinin and prostaglandins, not only in inflammation, but also in other systems. 4. Bradykinin stimulates phospholipase A2, thereby making available prostaglandin precursors.


Anaerobic Infections.

Anaerobic Infections. Oxygen-sensitive anaerobic bacteria comprise the largest group of organisms among the human endogenous microflora. The oral cavity, the vagina and the colon are areas where the obligate anaerobes are predominant and can be isolated in high numbers. Clinical clues that indicate anaerobic sepsis include a putrid odor of the exudate and evidence of abscess, necrosis or associated gas formation. A Gram stain is highly valuable in early identification. Surgical drainage and appropriate antibiotics are essential.


New evidence for inferoposterior myocardial infarction on surface potential maps. Extensive body surface potential recording was performed in 22 patients 2 to 4 weeks after an acute inferoposterior myocardial infarction. Serial isometric projection maps were viewed millisecond by millisecond throughout ventricular excitation, and a second series of maps were examined after removal of the expected range of normal potential distribution. Three major findings outside the normal range appeared: (1) In 6 patients, an early zone of abnormal positivity developed in the left anterior chest at xiphoid level between 15 and 30 msec after onset of the QRS complex; (2) in 13 other patients, a large zone of positivity developed high on the left anterior chest (subclavicular region) between 30 and 60 msec after QRS onset; and (3) in 8 patients the long-lasting rim of negativity about the lower chest was strictly abnormal compared with the expected range. Thus, in 19 of 22 patients the potential map expression was outside the normal range, whereas only eight standard electrocardiograms revealed persistent Q waves with a duration greater than 30 msec. We believe the mid and late activation changes are related to ischemically induced alterations in the temporal sequence of ventricular excitation, not easily appreciated by conventional means of recording but obvious with the departure map technique.


Functional differentiation of the chick endocrine pancreas. II. The alpha cells and glucagon. A radioimmunoassay for glucagon, together with electron microscopic observations of early embryonic alpha cells were utilized to examine developmental aspects of glucagon accumulation and release in the chick embryo. Immunoreactive glucagon was detected in both the pancreas and blood plasma from the fifth embryonic day onwards. In addition, emiocytotic events were observed in alpha cells as early as the fifth embryonic day. The early appearance of glucagon and its subsequent developmental profile correlate well with major events in carbohydrate metabolism occurring in the embryonic chick, and are discussed in relation to a functionally responding system, the developing liver. The present data show that glucagon is secreted at earlier embryonic stages than hitherto demonstrated, and suggest a developmental role for glucagon in hepatic glycogen metabolism.


Comparison of mouse liver sections and cultured mouse fibroblasts as substrates for the detection of antinuclear antibodies. Immunofluorescent antinuclear antibody tests were performed on selected sera representing various connective-tissue diseases using mouse liver sections and mouse connective-tissue fibroblasts cultivated in vitro. Substrate sensitivities and patterns of staining were compared by indirect immunofluorescent method employing sera from 92 patients. Sensitivity (geometric mean serum endpoint titer) was significantly greater with the cultured cell substrate. This greater sensitivity was also detected with sera from 46 patients with systemic lupus erythematosus (SLE). No significant difference was observed in other clinical groups tested (rheumatoid arthritis, polyarthritis, drug-induced SLE, degenerative joint diseases, and progressive systemic sclerosis). Sera from 107 to 109 normal controls were negative on the mouse fibroblast substrate. The two substrates were equally sensitive in detecting homogenous, peripheral, or speckled patterns of fluorescence in patients' sera having antinuclear activity. Nucleolar staining was observed in only one serum specimen as a minor pattern. Neither substrate demonstrated a predominant immunofluorescent pattern with sera from SLE,  polyarthritis, and progressive systemic sclerosis. Sera of patients with clinically diagnosed rheumatoid arthritis, drug-induced SLE, and degenerative joint diseases usually manifested monogeneous staning patterns. However, these differences in staining  pattern among the various clinical groups were not statistically  significant. The mouse tissue sections of equal specificity and significantly increased sensitivity for the detection of antinuclear antibody.


Demonstration in vitro of postmortem bacterial transmigration. The kinetics of the migration of intestinal bacterial flora to the peritoneal cavity upon death of the host was studied. A laboratory experiment that excluded any source of contamination was used. Samples of sterile saline solution in which a loop of the intestine was submerged were streaked onto blood agar at given intervals. Recovery of bacteria began after about 15 hours, with Staphylococcus aureus being the predominant organism. This organism showed a gradual decrease through a 36-hour period and at 48 hours was almost absent. In the same manner, other organisms such as gram-negative bacilli and spore-forming gram-positive bacilli gradually increased in numbers.


A simple method for maintaining fastidious organisms. Many strains of nutritionally fastidiuos organisms and anaerobes have been maintained in glycerol broth at-50 C for at least two years without loss of viability. This method of preservation offers convenience and reduces cost.


Pneumonia in the neonate associated with group B streptococcal septicemia. Fifteen newborns referred to the University of Utah Neonatal Intensive Care Unit (NICU) between 1971 and 1974 had septicemia and bronchopneumonia caused by streptococci of Lancefield group B. Eight of these infants could not be distinguished from others with idiopathic respiratory distress syndrome. All eight died and at autopsy were found to have bronchopneumonia. At autopsy, five of the ten subjects had bilateral pleural effusions. Eight of these early onset infections were caused by type III strains, three by type II strains, and four by Ia strains. The three survivors were infected by Ia organisms; two of these patients received antimicrobial therapy within one hour of birth and the other was treated at 20 hours of age. Among the 12 patients who died, six received no antibiotics and five were treated 12 or more hours after delivery. Earlier recognition may lead to more efficacious therapy of this most fulminant infection of the newborn.


Neonatal jaundice.

Neonatal jaundice. This article discusses the production, transport, and excretion of bilirubin in the newborn period. The causes, significance, and treatment of unconjugated and conjugated hyperbilirubinemia are different; and because this is so, it is important to review the main causes and management of unconjugated hyperbilirubinemia. Conjugated hyperbilirubinemia in the newborn period could be either due to hepatocellular dysfunction or extrahepatic biliary obstruction. There are several recent advances in early differentiation and management of these two entities.


Experience with synthetic secretin in the treatment of duodenal ulcer. Hospitalized male patients with endoscopically verified duodenal ulcer were studied to determine the effect of secretin on the clinical course of their disease. Seven patients received synthetic porcine secretin, 333 mug subcutaneously every 4 hr for 10 days, and 6 patients received placebo injections on the same schedule. Repeat endoscopy was performed within 48 hr of completing the 10-day treatment period. The trial was discontinued because of transient, asymptomatic, hyperamylasemia in secretin-treated patients. Although significant gastric alkalinization could be reproducibly demonstrated in secretin-treated patients, secretin was not more effective than placebo in relieving pain or healing duodenal ulcer. However, because the number of patients was small, definitive conclusions regarding efficacy of secretin in ulcer treatment could not be drawn.


The use of d-limonene preparation as a dissolving agent of gallstones. The dissolving mixture is administered through a choledochal drain to treat postoperatively retained cholesterol gallstones. It is prepared by mixing 97.0 parts of d-limonene with 2.1 parts of polysorbate 80 and 0.9 part of sorbitan monooleate, a mixture of which may easily reach the surface of the gallstones which are wetted by bile. The d-limonene preparation was found to be safe both in laboratory experiments and clinical trials. Before applying the preparation, the usual choledochal drain must be replaced with a recently developed catheter made from epichlorohydrine rubber, which is chemically resistant to the preparation. Three cases of retained gallstones are described where the preparation was successfully used. In the fourth case treatment with the preparation was tried in lieu of surgery but was not successful due to other complications. However, some dissolution of retained stones was observed. There were no postoperative complaints in the long-term follow-up of some cases for more than 2 yr after treatment with the preparation. This procedure promises to be of value because retained cholesterol stones may be dissolved without the necessity of further surgery.


The volumetric measurement of gastric emptying and gastric secretion by a radioisotope method. Most methods of measurements of gastric emptying rely on the serial estimation of intragastric volume and do not separately account for the volume of fluid which has been added to the meal by gastric secretion, duodenal reflux, or swallowed saliva. The volume emptied is therefore underestimated. A method of measuring gastric emptying using [125I]RIHSA and the Volémetron is presented. The volume of fluid added to the meal is taken into consideration in this method, giving a more accurate reflection of gastric emptying. Using this method in the dog, emptying was found to be linear rather than exponential.


Acute gastric mucosal injury during continuous or interrupted aspirin ingestion in humans. The effect of continuous versus interrupted high-dose aspirin (ASA) for 14 days was evaluated in a randomized double-blind study in 8 rheumatoid arthritis patients. Acute gastric mucosal injury was measured by serial gastroscopy and gastric biopsy. Significant gross mucosal damage was seen in all patients following 3 days of ASA (P less than 0.01) and persisted without significant change in severity to the end of the study. Histologic gastritis in areas free of hemorrhages and erosions was not increased significantly by ASA. In spite of gross mucosal injury, symptoms occurred infrequently. Serum pepsinogen I, but not serum gastrin, increased significantly following 3 days of ASA, and the elevation persisted to the end of the study. The extent of mucosal injury at 14 days was not significantly different in those receiving ASA continuously from those on an interrupted schedule. Thus, gastric mucosal adaptation to ASA in man was not demonstrated.


Shigellosis in the United States: ten-year review of nationwide surveillance, 1964-1973. In the 10 years 1964-1973, 105,832 isolations of shigellae were reported to the Center for Disease Control through a nationwide surveillance system. The number reported increased by approximately 13% annually, from 5852 in 1964, when only 17 centers reported all 4 quarters; to 16,797 in 1973, when 52 centers reported each quarter. The rate of reported isolations varied from 4.6 per 100,000 persons in 1965 to 9.1 per 100,000 in 1973. Shigella sonnei accounted for 64% of all these isolates and for more than 80% of isolates in 1973. The majority of reported cases of shigellosis occurred in young children and in women of childbearing age. During the 10-year surveillance period, 35 epidemics in 25 states were investigated. Two-thirds of these outbreaks were the result of person-to-person spread; investigations of common-source outbreaks showed the importance of both water and foodstuffs, especially salads, as potential vehicles of contamination. Indian reservations, custodial institutions, and day-care centers were identified as special high-risk settings for the transmission of shigellosis. The emergence of R-factor-mediated antimicrobial-resistance patterns in recent years has necessitated antibiotic sensitivity testing to determine the drug of choice for treatment of individual cases. Initial testing of oral vaccines suggests these vaccines will have only limited usefulness in protecting certain high-risk populations. Public health education coupled with improvements in water and sewerage systems remains the most satisfactory means of control.


The diagnosis of beta-thalassemia trait: a review. Diagnostic and screening methods for beta-thalassemia trait are reviewed in the order of their development, including identification by homozygous offspring, erythrocyte morphology, osmotic fragility, hemoglobin composition, globin synthetic rates, and red blood cell indices.


Current drug therapy--cephalosporins.

Current drug therapy--cephalosporins. The following aspects of cephalosporins are reviewed: chemistry and stability; mechanism of action; spectrum of activity; resistance; absorption, distribution, metabolism and excretion; uses; cautions; drug interactions; laboratory test interferences; and dosage.


Clinical use of oral hypoglycemic agents. The pharmacology, mechanism of action, indications, interactions and clinical effectiveness of oral hypoglycemic agents, specifically the sulfonylureas and biguanides, are reviewed. The use of these agents is discussed in view of the findings of the University Group Diabetes Program study. It is concluded that oral hypoglycemic agents, in conjunction with diet and weight reduction, may be useful in selected patients but that insulin is preferable in most instances.


System for clinical pharmacokinetic monitoring of theophylline therapy. A system was developed for guiding theophylline therapy in acutely ill patients with respiratory disease and for recovery of pharmacokinetic information. A dosage regimen nomogram was designed based on literature data and preliminary pharmacokinetic studies in patients. Using the nomogram, physicians select the loading and infusion dosages based on previous therapy, body weight, age, and cardiac and hepatic status of the patient. Specifications are provided for loading (up to 5.6 mg/kg) and maintenance doses (0.9, 0.68, or 0.45 mg/kg/hr) of aminophylline, handling of i.v. dosage forms, and collection of three initial blood samples. Serum samples were assayed for theophylline by high-performance liquid chromatography for rapid feedback of data to the physician and computer estimation of body clearance values. The usefulness of the nomogram guidelines was examined prospectively in 72 patients. Near-steady-state serum concentrations in the therapeutic range of 8-20 mg/liter were found in 72% of the patients. Only two patients were outside of the range of 5-25 mg/liter. The relationship between the physician's estimate of the patient's clinical status (three classes) and measured body clearance was highly significant (p less than 0.025). A comprehensive data collection format allows further analysis of the factors responsible for the variability in theophylline disposition in patients undergoing therapy.


The cardiovascular effects of lithium in man. A review of the literature. The medical literature since 1900 has been reviewed to determine the nature of lithium's cardiovascular effects. In therapeutic doses, lithium produces reversible T wave flattening and inversion in the electrocardiogram: rarely, it may cause sinus node dysfunction or ventricular arrhythmias. Patients with lithium toxicity almost always present with neurologic signs and symptoms. "Hypotension and cardiovascular collapse," alleged cardiotoxic manifestations of lithium, invariably follow days of coma. Given the possible cardiotoxic effect other psychopharmacologic agents and the hazards of withholding effective therapy in mania, it is concluded that lithium may be used safely in patients with cardiac disease if the dose is adjusted to the rate of lithium excretion and if serum levels of lithium are followed carefully. When used in patients with cardiac arrhythmias, frequent electrocardiographic monitoring is advised.


Post-transplant malignant lymphoma. Distinctive morphologic features related to its pathogenesis. Malignant lymphoma developed in two patients after renal transplantation. In both, the central nervous system was involved. Histologic study of the tumors showed that they were composed of a monomorphous proliferation of cells characterized by a large vesicular nucleus, prominent basophilic nucleolus and strongly pyroninophilic cytoplasm. The tumors thus would be classified as "diffuse large lymphoid lymphomas with pyroninophilia" or "immunoblastic sarcomas" as described in the literature. Tumor cells resembled cells observed in the paracortex of antigenically stimulated lymph nodes, cells from malignant lymphomas in mice that were antigenically stimulated and from malignant lymphomas in patients with immunodeficiency diseases or autoimmune disorders. The distinctive morphologic features of the tumors in the transplant recipients described provide further evidence that long-term antigenic stimulation may be important in their pathogenesis.


Formalin pigment (acid hematin) and related pigments. Black to brown amorphous to microcrystalline granules are encountered in histologic sections prepared from tissues fixed in formalin having a low pH. This pigment is produced by acid acting upon hemoglobin and is known as formalin pigment or acid hematin. A similar pigment is also observed in sites of bleeding ulcers in areas of acid production such as the stomach. These pigments exhibit many physical and histochemical properties similiar to pigments produced by some animal parasites as in malaria, schistosoma and pulmonary mites. These parasites disintegrate erythrocytes in an unknown manner, and liberate an acid hematin-like pigment which is phagocytized by the reticuloendothelial system. Since formalin pigment can be considered as an artifact, confusion with other pigments can be avoided by the use of neutral buffered formalin for the fixation of tissues.


The effect of antibiotic prophylaxis on patients undergoing total abdominal hysterectomy. I. Effect on morbidity. A prospective, double-blind study was conducted to evaluate the effect of cephalosporins on morbidity of women undergoing total abdominal hysterectomy. Each patient received a 5 day course of active drug or placebo beginning the night before surgery. Microbiologic studies, including culture and antibiotic sensitivities, were done on each patient pre- and postoperatively. Of the 46 women who received placebo, eighteen (39 per cent) were classified as morbid. Causes of morbidity included operative bed, wound, respiratory, or urinary tract infections. E. coli was the organism most frequently isolated. Of the 47 women who received cephalosporin prophylaxis, seven (15 per cent) were classified as morbid. The causes of the morbidity were often poorly defined, and cephalosporin-resistant organisms were recovered more often from these women than from those on placebo. There was no significant difference in length of hospital stay between women who received prophylaxis and those who did not.


Studies on the gonadotropin response after administration of LH/FSH-releasing hormone (LRH) during pregnancy and after therapeutic abortion in the second trimester. The gonadotropin response to synthetic LH/FSH-releasing hormone (LRH) was found to be suppressed in the second trimester of pregnancy. The basal levels of plasma FSH were very low and no detectable increase occurred after injection of up to 500 mug LRH intravenously. Five of the women were then tested with 25 mug of LRH intravenously on three occasions during the first month after therapeutic abortion in the second trimester. A rapid normalization of the basal plasma levels of FSH and LH and of the response to LRH occurred. This is in contrast with the pattern after term pregnancy. The possible role of different hormones and of the duration of pregnancy (duration of inhibition) as an explanation for this discrepancy are discussed.


Effect of terbutaline on premature labor. A double-blind placebo-controlled study. The effect of terbutaline, a "selective" beta2-receptor stimulator, was compared with that of placebo in 30 patients in premature labor. Treatment consisted of an intravenous infusion for at least 8 hours, and then of subcutaneous injections four times daily for 3 days together with peroral treatment, which was continued until the end of week 36 of pregnancy. In 12 of 15 terbutaline-treated patients (80 per cent) premature labor was arrested beyond the treatment period, compared with three of 15 in the placebo group (20 per cent). This difference is statistically significant (p less than 0.01). No serious side effects were observed. During infusion, there was an increase in maternal heart rate. This was more pronounced in the terbutaline group (30 per cent) than in the placebo group (9 per cent). There were no adverse effects on blood pressure, but fetal tachycardia was observed more frequently in the terbutaline than in the placebo group. The results suggest that terbutaline is a safe, potent, and well-tolerated inhibitor of premature labor.


The primary treatment of breast carcinoma. The major contribution in the surgical management of carcinoma of the breast have been reviewed. Deficits in our current knowledge have been pointed out in an effort to separate fact from theory and so help the surgeon in choosing the best operation for a patient with breast cancer.


Hepatitis B antigen: a review of its importance in the practice of obstetrics and gynecology. Surgeons engaged in the practice of obstetrics and gynecology should have a clear understanding of the hepatitis B antigen (Australia antigen) serologic test. When positive, it serves as a marker either for the carrier state or for subclinical to overt hepatitis B (serum hepatitis). Patients or health personnel with a positive test are potentially infectious and appropriate precautions should be taken. Surgeons are at increased risk for hepatitis B and, when acutely exposed, should receive standard serum globulin, or perhaps high-titer hepatitis B immune globulin in the future. Infants born to mothers with a positive test may become hepatitis B antigen positive and develop chronic hepatitis.


Annual review of retinal research.

Annual review of retinal research. This paper reviews recent ophthalmological manuscripts pertaining to wasting retinal nerve fibers, retinopathy related to systemic lymphomas, hypertensive retinopathy, diabetic retinopathy, retinal oxalosis, macular and foveal anomalies, retinal pigment epithelium, retinitis pigmentosa, retinoblastoma, histoplasmosis, toxoplasmosis, and retinal tears and detachments.


Surgical-orthodontic expansion of the maxilla. Selected maxillary osteotomies are safe and dependable adjuncts to treatment of bilateral and unilateral maxillary deficiency. Maxillary expansion in fifteen adults was accomplished by separating the maxillary basal bone from the nasal, zygomaticomaxillary, and pterygomaxillary buttresses.


Phosphoric acid penetration during direct bonding. This work has investigated the actual penetration of acid etching material into the enamel surface as it is used in preparation for the direct-bonding adhesive. Three important conclusions can be drawn from this investigation. (1) Rinsing does not necessarily completely arrest the acid etching process in the depth of the exposed enamel. (2) The effect of the acid etching material does seem to be deeper than 10 mu, which is contrary to the manufacturers' statements. There is (3) no evidence of actual penetration of the acid etching material at the dentinoenamel junction.


Shear strength of orthodontic direct-bonding adhesives. A total of 210 double-width stainless steel edgewise brackets with retentive lip bases were bonded to bovine incisors with seven commercially available direct-bonding materials. Ten samples for each of the seven direct-bonding materials were tested for shear strength using the Instron Universal Testing Instrument. The samples were tested after 1 day, 1 month, and 3 months of immersion in 30 per cent physiologic saline solution. The mean shear strength of each direct-bonding material at each time interval was compared statistically to the mean shear strength of each of the materials at each time interval with a matched 1 test. The same test was used to determine whether there had been a significant change in mean shear strength from start to finish of testing for each material. One product showed a significantly better mean shear strength than any other material at each test interval. The remaining materials were grouped in middle or low ranges, depending upon their final mean shear strengths and degrees of nonsignificance when compared to each other.


Extracellular calcium and adrenergic and cholinergic effects on islet beta-cell function. An in vitro perifusion system utilizing collagen-medium calcium on the dynamics of insulin release as induced by acetylcholine (ACh) stimulation (in the presence of glucose, 2.4 mM) and as modified by prior perfusion of islets in epinephrine. Continuous challenge with ACh produces a biphasic insulin release response, both phases of which are reduced when the medium calcium concentration is reduced during stimulation; when the calcium content is reduced during an initial perifusion period of 30 min and then replaced during subsequent stimulation only the first phase of the response to ACh is affected; perifusion with epinephrine prior to stimulation with ACh produces enhancement of both phases of ACh-induced insulin release when calcium in both media is normal. However,.when this experiment is repeated utilizing a medium with low calcium content during the period of exposure to epinephrine the priming effect of epinephrine on the subsequent insulin response to ACh is abolished (in fact, reversed). These studies provide direct evidence for a role for calcium in mediating an effect of epinephrine on insulin release. Further, the data suggest that epinephrine affects Ca transport in islets in some manner beyond stimulating net efflux from islets, perhaps by enhancing membrane binding of calcium.


Child custody contests in historical perspective. The author reviews the historical background of interparental child custody disputes. The father's superior right to custody in the nineteenth century continued the English common law tradition, but in the twentieth century the mother's claim became superior to the father's, reflecting women's generally increasing rights and the assumption that women are better suited to caring for children. Partly as a result of recent cultural changes leading to a beginning equalization of parental rights and partly because of greater concern for children, courts are starting to focus more on children's emotional needs. It is likely that courts will increasingly call on psychiatrists and other mental health professionals for help in making their decisions.


Routine on-line psychiatric diagnosis by computer. With the advent of effective psychiatric treatments, greater accuracy in psychiatric diagnosis has become a vital concern for psychiatric training, research, and patient care. The authors have adapted current computer diagnostic procedures in order to obtain highly accurate diagnosis while simplifying and shortening the process of information input and diagnostic output. Their program requires a minimum of the clinician's time and provides feedback during the diagnostic process when the clinician requires it. The authors believe that routine use of this computer diagnostic program will improve psychiatric training, research, and patient care.


1976 Anniversaries.

1976 Anniversaries. The author recalls this year's anniversaires of events and individuals prominent in the history of medicine, psychiatry, and psychology and examines their practical or theoretical contributions.


Tapering off of tuberculosis among the elderly. Tuberculosis has long been prevalent among elderly people. When tubercle bacilli first enter human bodies they usually remain through the rest of their hosts' lives and are capable of causing clinical disease any time, even in old age. In 1900, a large percentage of people of all ages were harboring tubercle bacilli and high mortality and case rates obtained among elderly people. The only way to solve the problem among future old people was to protect infants, children, and youths from becoming infected and remain so throughout life. As far as possible that was accomplished by isolating and treating tuberculosis patients in sanatoriums and hospitals, with anti-tuberculosis drugs after 1946, and controlling the disease among cattle. In due time, large numbers of children entered adulthood uninfected. From year to year, they replaced those heavily infected as they advanced in years. By 1973 the mortality rate was only a fraction of 1.0 per 100,000 among people under 34 years but of those of 65 to 84 years it was 9.7. The case rate was 28.1 for those older than 45 years. Although tuberculosis among the elderly has tapered off phenomenally, much time and work are necessary to accomplish eradication.


Distribution of gastrin in canine, cat, and human digestive organs. In dogs, cats, and humans, gastrin-containing cells were found only in the antrum and in the duodenum by specific direct immunofluorescence. Distribution within the human duodenum, however, differed from that in cats and dogs. No gastrin-containing cells were seen in other sites of the body.


Primary tumors of the mandible. A study of 49 cases. Forty-nine cases of primary tumors of the mandible have been reviewed. The anatomic location, pathologic features, sites of metastases, survival rates, and treatment methods were evaluated. Lesions studied included ameloblastoma, osteogenic sarcoma, reticulum cell sarcoma, fibrosarcoma, chondrosarcoma, myxosarcoma, epidermoid carcinoma, adenocarcinoma, and giant cell sarcoma. An in-depth discussion of primary osteogenic sarcoma of the mandible is presented. Because of upper cervical lymph node metastases in two cases of osteogenic sarcoma of the mandible, an upper neck dissection should be considered in the primary treatment. Also presented in this study are the first reported cases or primary myxosarcoma of the mandible and giant cell sarcoma of the mandible. Recent methods of treatment of ablative resection of the mandible followed by immediate or delayed repair are discussed. A revised technic for mandibular replacement which has met with success in six of seven cases is presented.


Intramesenteric perforation of sigmoid diverticulitis with nonfatal venous intravasation. Complications from barium enema are rare (0.035 per cent). A patient with venous intravasation during barium enema complicated by pylephlebitis and portal vein obstruction is the tenth to be reported on, the fourth to survive. This accident was associated with colon disease in eight of the patients studied, five of whom had diverticular disease.


Sternal wire closure by an instrumental method. Effective median sternotomy closure requires approximation of the sterum under appropriate tension in an expeditious manner. An instrument has been developed to provide tightening of applied sternal wires, allowing proper tension to be established. After tightening, the twisted wire is automatically trimmed by the instrument. The ease and reproducibility of this wire closure technic has allowed the method to be performed on a routine basis.


A simple method of rapid and atraumatic removal of hemostatic clips. A simple method of atraumatic removal of hemostatic clips is described employing the use of a diagonal cutting pliers. This method is equally effective for the removal of small, medium, or large hemostatic clips.


Routine evaluation of endothelium in human donor corneas. Specular microscopy allows a direct evaluation of the corneal endothelium in intact donor eyes. It is therefore superior to previous methods for assessing donor material for penetrating keratoplasties. In a study of 278 eyes (139 donors) 226 could be examined by specular microscopy without any preparatory major manipulations. Twenty-four pairs and 12 single eyes (27%) of the 226 corneas were considered not suitable for grafts according to their morphologic endothelial changes. The discarded eyes were found all normal at conventional slit-lamp examination. Specular microscopy of the endothelium was not possible in 52 eyes as the corneal swelling was already too advanced.


Endothelial changes in human donor corneas. The corneal endothelium of intact donor eyes was evaluated by means of a specular microscope. In a series of 278 corneas, different morphologic changes were found in the endothelium. These changes are described and systematically classified. The findings are analogous to results obtained on experimental animals and with light- and electron-microscopic studies of other authors.


Effect of somatotropin upon a freshwater fish, Channa punctatus (Bloch). The mammalian growth hormone was administered intramuscularly to a freshwater teleost, Channa punctatus. The hormone induced a mild hyperglycemia lasting 120 hours. The beta cells in the pancreatic islets showed degranulation due to exhaustion.


Localization of transferrin on the surface of the human placenta by electron microscopic immunocytochemistry. During the course of gestation, a large amount of iron is transferred rapidly and unidirectionally from mother to fetus across the placenta. It has been postulated that one of the first steps involved in placental iron transfer involves binding of the maternal transferrin-iron complex to the surface of the placenta and the subsequent removal of iron and release of transferrin back into the maternal circulation. To determine if transferrin is present on the surface of human placental villi, two different immunocytochemical methods have been used: (1) an unlabeled antibody, peroxidase-antiperoxidase (PAP) method utilizing rabbit antiserum to human transferrin, goat anti-rabbit IgG and rabbit peroxidase-antiperoxidase complex or; (2) a peroxidase-labeled antibody method utilizing goat antiserum to human transferrin and peroxidase-conjugated rabbit anti-goat IgG. The peroxide was then localized by incubation in a diaminobenzidine-hydrogen peroxide medium. Examination of the tissue in the electron microscope revealed the reaction product deposited as discrete patches or particles on the microvillous surface of human syncytial trophoblast. Controls using non-immune serum or an antiserum adsorbed with purified human transferrin showed no reaction product on the surface. The results provide morphological confirmation for the presence of transferrin on the surface of human syncytial trophoblast lining the maternal blood spaces.


On the postcycle parasitism in helminths and its biological significance. A generalization of the existing data is being done in the work concerning the postcycle parasitism and the postcycle hosts in helminths. So far postcycle parasitism has been observed in various trematodes, cestodes and nematodes parasitizing the digestive tract of vertebrates. The biological significance of the phenomenon comes to the following: survival of mature helminths when they find themselves in the digestive tract of the postcycle hosts; accumulation of such helminths in some cases; and a probable promotion to convert some postcycle hosts into final hosts, too (in historical aspects).


Pemphigus and pemphigoid: dermatologic examples of type II immune reactivity. Pemphigus is an erosive disease of the skin and mucous membranes, characterized by intraepidermal blisters, acantholysis of epidermal cells and a serum antibody directed to an antigen at the intercellular space. Pemphigoid is a bullous disease primarily of the skin and usually seen in older individuals. The blister forms beneath the epidermis and the serum antibody is directed to the basement membrane zone. Both diseases may require systemic corticosteroids or cytotoxic agents for control.


Antibiograms of streptococci isolated from bovine intramammary infections. A total of 455 streptococcal cultures from bovine intramammary infection in 72 herds were studied to determine their sensitivity to 17 antimicrobial agents. More than 90% of the cultures were sensitive to carbenicillin, chloramphenicol, erythromycin, and penicillin. Gentamicin, neomycin, nitrofurazone, polymyxin, and streptomycin were ineffective in the in vitro inhibition of streptococci.


In vivo spread of infectious drug resistance in turkeys. Multiresistant Salmonella typhimurium donor and multisensitive Escherichia coli recipient spread from the infected group of turkey poults to the control group. Contact poults given only the S typhimurium donor and placed in the same cage with infected poults given both the donor and the E coli recipient exhibited in vivo patterns of antibiotic drug resistance transfer similar to the patterns obtained in the infected poults. This in vivo spread of antibiotic drug resistance in turkeys was established for the first time. Results indicated that the potential in vivo spread of infectious drug resistance could occur in nature.


Development of immunoglobulin-containing cell populations in intestine, spleen, and mesenteric lymph node of the young pig, as demonstrated by peroxidase-conjugated antiserums. Peroxidase-conjugated antibody to porcine immunoglobulins A, G, and M were used in a light microscope study of the development of immunoglobulin-containing cells in small intestine, spleen, and mesenteric lymph node of the young pig. Many cells staining for each of the 3 immunoglobulin classes were present in duodenum of 1-week-old-pigs, and the number increased in succeeding weeks. Immunoglobulin M cells outnumbered immunoglobulin A cells in the 1- to 3-week-old pigs, after which immunoglobulin A cells predominated. Immunoglobulin G cells were present in considerable but smaller numbers at all ages. Stained cells in spleen and mesenteric lymph node were not detected until after pigs were 1 week old.


Antibacterial host defense: in vitro interaction of bacteria, serum factors, and leukocytes from precolostral dairy calves and their dams. The bactericidal capacity of serum and peripheral blood leukocytes from newborn dairy calves (before receiving colostrum) and their dams for a strain of Escherichia coli and Staphylococcus aureus has been investigated. Comparative studies were conducted, using either unheated (freshly collected) and heated serums alone or in combination with cells from adult and newborn animals. Neither serum from newborn calves was able to kill either microorganism. Both microorganisms were sensitive to bactericidal activity of antibody and complement in unheated serum from adult cattle. On heating, serum from adult cattle lost bactericidal properties of the antibody-complement system. A cellular deficiency in phagocyte function in cells of newborn dairy calves was not evident, since they were as able to kill E coli and S aureus as cells from adult cattle, when incubated in the presence of the same opsonic source. Bactericidial activity was not evident when cells from newborn calves were incubated with heated autologous calf serum and S aureus or E coli. Unheated, autologous calf serum combined with cells from newborn calves exerted bactericidal capacity against S aureus but not E coli. The bactericidal capacity against S aureus of cells from newborn calves incubated with unheated serum from newborn calves did not differ from heated serum from adult cattle. However, there was a difference with E coli. The reasons for this phenomenon have not been determined, but may relate to natural, specific immunity of the neonate. Immunoglobulin and antibody concentrations in serums from calves and dams were determined. Most of the dams had bacterial agglutination titers to both microorganisms; the calves had either undetectable or low levels of antibody.


Trimethoprim-sulfamethoxazole therapy of pulmonary melioidosis. A 21-year-old-airman stationed in the Philippines presented with cavitary pulmonary melioidosis. When treated with trimethoprim-sulfamethoxazole, there was prompt resolution of his symptoms and the left upper lobe abscess cavity. It is suggested that this antimicrobial combination is an effective alternative regimen for pulmonary melioidosis.


Human oral defenses against gram-negative rods. Gram-negative rods are unusual pharyngeal isolates in normal man, which suggests the presence of effective oral defense mechanisms against these organisms. To understand this protection better, we studied the elimination of gram-negative rods from the mouth after gargle challenge. Suspensions of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (108 organisms per ml) were gargled by normal volunteers, and pharyngeal swabs for serial quantitative cultures were taken for 3 hours. Initial swabs yielded approximately 10(5) organisms. Bacterial counts rapidly decreased, and less than 1 per cent of the original inoculum was still recoverable 3 hours later. Studies of tongue, pharynx, and buccal mucosa samples showed the most rapid decrease in buccal mucosa samples and the slowest decrease in tongue swabs. To evaluate physical clearance, gargle challenges were performed using E. coli radiolabeled with technetium-99m. External counts of the oral cavity decreased rapidly, with 21.8, 14.7, 8.9, and 7.8 percent of the initial counts remaining at 30, 60, 120, and 180 min, respectively. Nonpiliated E. coli adhered poorly to buccal epithelial cells in vitro, in contrast to good adherence when piliated strains were tested. Despite these findings, no differences in radiolabel clearance was noted in vivo using piliated and nonpiliated E. coli for gargle challenges. Normal oral defenses against gram-negative rods are highly effective and seem to involve both physical clearance and local bactericidal activity.


In vivo and in vitro cell-mediated responses in coccidioidomycosis. I. Immumologic responses of persons with primary, asymptomatic infections. Chest roentgenograms of 58 children who were skin test positive to coccidioidin and resided in an area endemic for coccidioidomycosis revealed that 34 per cent had roentgenographic evidence of an inflammatory process, 14 per cent showed calcific densities, and 52 per cent showed no evidence of infection. The in vitro lymphocyte responses of children who had evidence of an inflammatory process (Group I) were compared with those of children who had calcific densities (Group II); those of children who were coccidioidin skin test negative and had normal chest roentgenograms (Group III); and those of patients who had active coccidioidomycosis (Group IV). The mean lymphocyte transformation responses (expressed as cpm times 10-(4)) of Groups I, II, III, and IV to a coccidioides antigen were 16.8, 19.5, 4.2, and 7.0, respectively. The mean migration inhibitory factor responses of these groups were 22.4, 20.0, 1.2, and 4.0 per cent, respectively. Thus, the over-all responses of children in Groups I and II were comparable to each other, whereas the responses of patients in Group IV were depressed to the extent that they were indistinguishable from those of coccidioidin skin test-negative donors in Group III. Follow-up chest roentgenograms taken 3 months after the immunologic assays were performed revealed that the one subject in Group I who had been nonresponsive  in the lymphocyte assays had now stabilized his infection, as evidenced by calcifications. In contrast, the 2 subjects in Group I who had yet to stabilize their infection had exhibited strong in vitro lymphocyte responses. These findings suggest that primary, asymptomatic coccidioidomycosis is not associated with an immunologically nonresponsive state. However, patients with active, progressive coccidioidomycosis do have a depressed immunologic response to coccidioides antigens.


The maximal expiratory flow-volume curve: its use in the detection of ventilatory abnormalities in a population study. Flow-volume and spirometric parameters obtained in a randomly selected population were examined with regard to their sensitivity in detecting abnormalities among persons who smoked and/or had respiratory symptoms. Data obtained from subjects who were totally free of cardiorespiratory symptoms and who had never smoked cigarettes were used to develop "normal" prediction equations. Using as normal limits the per cent of predicted value above which 95% of these "normal" subjects fell, maximal expiratory flow at 75% of the expired vital capacity (Vmax75) detected the greatest proportion of abnormalities in the remainder of the population. When examined according to age, however, Vmax75 was most sensitive in older subjects, whereas 1-sec forced expiratory volume was superior in younger subjects. There was a slight tendency for Vmax75 to be affected in subjects with reactive airway syndromes and for the 1-sec forced expiratory volume to be affected in heavy smokers or subjects with chronic productive cough. If one parameter was markedly abnormal, the entire flow-volume curve was likely to be affected, but concordance of the parameters examined was not complete. For the latter reason, considerable caution must be exercised in attempting to use multiple parameters in defining abnormality, unless one applies more stringent criteria for abnormality.


Studies in burns: XV. Use of a topical lipid in treating human burns. Sixty patients were selected from the 24-month burn population admitted to the Medical College of Georgia. Selection was on the basis of age, size of burn, and survival beyond 120 hours. Thirty-one of these patients were treated with ethyl linoleate agent (hELate) in addition to the modalities we routinely use for burn care. hELate was applied in a dose of 25 mg/kg only once in the period after burn. Significant pain relief and enhancement of wound healing (with return of hair and pigment) occurred in the hELate-treated patient. Less narcotic was needed, fewer grafts and reconstructive procedures were required, and hospital stay was reduced significantly. It is suggested that hELate is a safe and useful adjunctive to burn care.


Arterial embolism from a bullet: a case report. Accounting for each wounding bullet represents an important part of the emergency room evaluation of gunshot victims. Physical examination must include a thorough search for exit wounds. Medical personnel must be aware of the possibility of intra-arterial passage of a wounding missile and routinely obtain appropriate roentgenagraphic studies so that patients with arterial bullet embolization will be identified preoperatively and can receive optimal surgical repair of their injuries.


Immune-related renal vein thrombosis in a renal allograft. A patient developed a renal venous thrombosis 15 months after renal transplantation. In contrast to other cases described in the literature, the thrombosis was not related to vascular surgical trauma, but was immune-complex mediated. The patient's renal function stabilized and the nephrotic syndrome improved over 18 months follow-up during continuous oral anticoagulant therapy.


Betty Fothergill and her "Uncle Doctor". An intimate glimpse of Dr. John Fothergill. John Fothergill, M.D., (1712-1780) was one of the best-known physicians in London in the 18th century. He was a botanical collector, a philanthropist, and an active member of the Society of Friends. He entertained and advised a series of young doctors from the American colonies and strove with his friend, Benjamin Franklin, to avert the Revolutionary War, albeit unsuccessfully. A rare glimpse of Dr. Fothergill, the man, and his domestic life is given in the diary of his 17-year-old niece, Betty Fothergill, who spent the winter of 1769-70 in her uncle's household. Excerpts from the diary show him to be a liberal-minded man and one fond of the company of young people; and show Betty to be a sprightly young Quakeress, buffeted by emotional conflicts between loyalty to her north-country fiance and her flirtation with young Dr. John Coakley Lettsom.


Hydrophilic bandages in penetrating keratoplasty. A retrospective analysis was conducted of 100 consecutive cases of penetrating keratoplasty revealing that in 68% of the cases hydrophilic bandage lenses were applied at some time during the course of the operative procedure or postoperatively. In 4% of the cases, lenses were applied before the actual start of keratoplasty and in 13% the lenses were applied before the conclusion of the operative procedure. In 28%, the initial lens application occurred within the first 10 postoperative days while in 18% initial application occurred prior to the time of suture removal. In the remaining 5% of the cases, the lens was applied relatively late in the postoperative course. Primary indications for bandage lens application were prophylactic in cases of infants, chemical burns, exposure, and dry eyes. Therapeutic indications included surface drying and erosion, wound margin defects, patient discomfort, and inflammatory episodes.


Observations on laryngeal disease, laryngeal behavior and voice. This discussion accepted the hypothesis that every laryngeal sound is produced by its unique type of vocal cord vibration. The production of vocal sound is not capricious, it follows certain laws many of which are not known. Research into the behavior of the larynx has produced some interesting and perhaps, useful findings. It was the intention of this paper to describe some of the features of laryngeal behavior as they relate to both phonation and laryngeal disorders in the belief that such knowledge lends itself to the more efficient management of certain vocal and laryngeal problems. The central theme has been that it is laryngeal behavior and not laryngeal disease itself that determines vocal deviation.


Tracheostenosis and bronchial abnormalities associated with pulmonary artery sling. Three patients with aberrant left pulmonary artery (sling artery) are reported to illustrate associated tracheobronchial abnormalities. The clinical picture was that of severe episodic or progressive respiratory distress without dysphagia in early infancy. Striking narrowing of the trachea by complete "ring cartilages," unrelated to compression by the abnormal pulmonary artery, was present. Tracheotomy and intubation failed to relieve the obstruction. In one patient the bronchi and bronchial segmentation pattern were normal, but in the other two patients, bronchial abnormalities included wide irregular cartilages in the main bronchi, forming more complete rings than is normal. In both, the right main bronchus was relatively longer than normal, and the bronchus intermedius showed poor cartilage ring formation and was relatively short compared to the main bronchus. This discrepancy did not appear to be due to distal displacement of the right upper lobe bronchus. In these two patients the left main bronchus was relatively short and wide with reduced number of cartilage rings (five-six vs usual normal number of nine), so that the right and left main bronchi were almost of equal length. However, the branch patterns of the lobar bronchi were within normal range. Bronchoscopy seems essential to demonstrate such ring tracheal cartilages (absence of the pars membranacea of the trachea), which when found should alert the examiner to the possible presence of an abnormal left pulmonary artery. Since surgical correction of tracheal stenosis of this type is not possible at present, the ultimate prognosis of patients with sling artery may depend more on the severity of the tracheal anomaly rather than on success of surgical correction of the abnormal left pulmonary arterial course. Although aberrant (sling) left pulmonary artery can occur in patients without respiratory tract symptoms, tracheal stenosis due to ring tracheal cartilages occurs in a significant fraction of patients with this arterial anomaly. Bronchoscopic study of the trachea, and possibly air or contrast bronchography of right and left main bronchi, can be of aid in diagnosis of this complex.


Subglottic stenosis in infants and children. Of 158 cases of subglottic stenosis 115 were congenital and 43 acquired. Current follow-up has been obtained in 146 (92%) which constitutes the determinate group. Although stridor was the most common presenting symptom of the congenital group, 34% presented with recurrent or prolonged episodes of croup. Tracheotomy was required in 47 of the 107 determinate cases (44%). Further management of the congenital cases was based on the experience that children outgrow this disorder; periodic dilatation may augment the natural process. Of those infants and children tracheotomized, all but five have been decannulated, and there was one death - a mortality rate of 2.1%. Acquired subglottic stenosis proved to be a more difficult management problem. Tracheotomy was necessary in 38 of the 39 determinate cases (97%). Repeated active dilatations for prolonged periods were usually required as well as endoscopic removal of granulation tissue. Of those infants and children tracheotomized, all but eight have been decannulated. There were nine deaths; five were due to unrelated underlying disease; four were attributable to complications of long-term tracheostomy. Thus, in the entire series, 85 infants and children required tracheotomy and five deaths may be attributable to long-term tracheostomy complications - a mortality rate of 5.9%.


Tracing the tracheostomy.

Tracing the tracheostomy. The evolution of tracheostomy can be divided into five stages. The first and longest period (covering roughly 3,000 years from 1500 BC to 1500 AD) begins with references to incisions into the "wind pipe" in the Ebers Papyrus and the Rig Veda. However, Alexander the Great, Asclepiades, Aretaeus and Galen are all recorded as having used this operation. Between 1546 with the writings of Brassarolo until 1883, the procedure was considered futile and irresponsible and few surgeons had the courage to perform it. The third period starts with Trousseau's report of 200 cases in the therapy of diphtheria in 1833. Tracheostomy became a highly dramatized operation for asphyxia and acute respiratory obstruction. In 1932 Wilson suggested its prophylactic and therapeutic use in poliomyelitis. Tracheostomy was then recommended for a large variety of assorted maladies. This started a tremendous period of enthusiasm. Finally, the present era starting in 1965 comes as a period of rationalization. Complications, indications and interrelation with endotracheal intubation are clearly outlined. Tracheostomy has found its place.


Educational training in endoscopy.

Educational training in endoscopy. An educational training need has developed as a result of the recent rapidly increasing acquisition of endoscopes. This acquisition has been occurring at a rate faster than training programs can acquaint physicians with their use. A Veterans Administration (VA) feasibility study has determined that color television-endoscopy can provide the type of instructional materials that could be used to assist a larger number of physicians in acquiring skills in endoscopy. Since the budget requirements for television-endoscopy are substantial, it seemed expedient for the VA to establish a Center for Endoscopic Programs (VACEP). The purpose of this Center is to prepare instructional materials that will enhance educational training in endoscopy. We believe that the provision of self-instructional and teaching supplement types of audiovisual materials are essential to the accomplishment of VACEP's educational objectives. Our society today is video oriented, and we believe very strongly in the value of the television medium as an educational adjunct in teaching endoscopy.