Human babesiosis on Nantucket Island: transmission by nymphal Ixodes ticks. In order to identify potential vectors of human babesiosis (Babesia microli) in southern Massachusetts, I attempted to transmit the infection via nymphal ticks of that species found to be most abundant on reservoir hosts (Peromyscus leucopus) in nature. Mice were collected at frequent intervals throughout a year in a known enzootic focus on Nantucket Island, and ticks were removed by hand. Ticks of only two species were present; larvae and nymphs of Ixodes scapularis were about 10 times as numerous as were those of Dermacentor variabilis. Accordingly, I. scapularis were used in attempts to transmit a strain of Babesia derived from a human infection recently acquired near the study site. Larvae were permitted to feed on an infected hamster and nymphs derived from these larvae were placed on each of 11 non-infected hamsters. All but one hamster became infected. Nymphs reared from larvae that had attached to a non-infected hamster did not transmit babesiosis to other hamsters. These results suggest that I. scapularis serves as a vector of babesios-s on Nantucket hamsters. These results suggest that I. scapularis serves as a vector of babesiosis on Nantucket Island.


Fatal human infection with mesocercariae of the trematode Alaria americana. A fatal human infection with mesocercafiae of Alaria americana is described. Several thousand mesocercariae were estimated to be present in the peritoneal cavity, bronchial aspirate, brain, heart, kidney, liver, lungs, lymph nodes, pancreas, retroperitoneal adipose tissue, spinal cord, spleen, and stomach. Nine days from the onset of symptoms death resulted from asphyxiation due to extensive pulmonary hemorrhage probably caused by immun-mediated mechanisms. Circumstances suggest the victim probably ate inadequately cooked frog legs while hiking. Mesocercariae penetrated through the stomach wall and spread to the various organs both directly and via and circulatory system.


Morbidity from Schistosoma mansoni infections: an epidemiologic study based on quantitative analysis of egg excretion in two highland Ethiopian villages. Although human infection with Schistosoma mansoni is known to be widespread in Highland Ethiopia, no information is available on its public health impact. A sample of the inhabitants of two typical villages in the endemic region north of Lake Tana were studied by clinical and quantitative parasitologic methods. One village had a moderately high prevalence (43.3%), while the second, chosen for comparison, had a very low prevalence (10.7%). No evidence of severe hepatosplenic disease was found in 343 persons examined. Symptons and mild hepatomegaly compatible with S. mansoni infection were common, and in the high prevalence village complaints of abdominal pain and blood in the stool were significantly related to S. mansoni egg counts. However, all signs and symptoms compatible with S. mansoni infection, including hepatomegaly, were of greater or similar frequency in the village with the low prevalence of infection. The findings of minimal morbidity are compatible with the level of intensity of infection found in the area and are consistent with the findings from morbidity studies based on quantitative egg counts in other areas of the world.


A modification of the formol-ether concentration technique for increased sensitivity in detecting Schistosoma mansoni eggs. The low Schistosoma mansoni egg counts generally found in Puerto Rico require a sensitive technique for epidemiologic studies. The Ritchie formol-ether concentration technique has been modified to make it more useful for this purpose. The modified technique was compared with the older technique by analyzing fecal specimens from ten individuals with varying levels of infection. It was also compared with the Kato thick-smear technique with specimens from 25 other patients. In both series, three replicates of each technique were done on each stool. Results indicated that the modified technique was more sensitive than the older technique in terms of number of eggs counted, and that the sediment was smaller and clearer and required about 15% less time to examine. In comparison with the Kato technique, it was more successful in detecting light infections, although at higher levels of intensity, when expressed on an eggs-per-gram basis, the thick smear detected relatively more eggs. For the series as a whole, coefficients of variation for the three replicates done on each stool were smaller for the modified concentration technique than for the Kato technique. This is interpreted to reflect satisfactory reproducibility of the concentration technique when compared to the Kato technique. The concentration technique has the additional advantages over the thick smear of detecting other intestinal parasites and allowing for transportation and storage after feces are preserved in formalin.


Influence of hycanthone on morphology and serotonin uptake of Schistosome mansoni. The intrinsic content of serotonin (5HT) and the uptake of 5HT by Schistosoma mansoni taken from mice which were given a single intramuscular therapeutic dose of hycanthone were studied. Drug-exposed worms were found to have intrinsic values of 5HT which were similar or slightly less than controls. Uptake measurements were made on single and on paired worms recovered from mesenteric, portal, or hepatic sites and incubated in 75% horse serum or in Fischer's medium. All groups of treated worms were found to take up, on average, similar or lower amounts of 5HT compared to controls. These findings are in contrast to a recent report of very considerable increases in content or in 5HT acquisition in vitro by hycanthone-exposed parasites. This communication suggests that the mode of action of hycanthone cannot be explained as being due to increased 5HT uptake. Morphological changes in hycanthone-treated worms include loss of body weight and size, loss of hemoglobin pigment from the gut, deterioration of the tegument, and derangement of the vitellaria. The loss of gut contents occurs early after exposure to hycanthone and may indicate that interference with gut physiology and the nutritional state of the worms is one consequence of the drug, although the mechanism of these changes has not yet been elucidated.


Hydatid cysts in children and youths.

Hydatid cysts in children and youths. In the 15 years from 1960 through 1974, 58 patients (38 male and 20 female) from 3 to 18 years of age were treated. In 24 only the lungs were involved, in 23 only the liver, and in 2 both organs were involved. Various other organs including the orbit, omentum, kidney, uterus, brain, and spinal cord contained cysts in one or more cases. Diagnosis was by X-ray, angiography, and myelography. The Casoni skin test was positive in 36 of 43 (83.7%) trials. All patients were treated surgically and, except for one death from pneumonia, all did well.


Fire on ice.

Fire on ice. Hockey is recognized as being one of the fastest and most demanding sports in the world, with a reputation for roughness and physical risk. The risk factor should be defined as the probability of the participant's sustaining injury. Because of our growing concern for the physical safety of both male and female ice hockey players at all age levels, this study was designed to: (1) examine the incidence of accidental and penalty-related injuries; (2) examine the nature and severity of the injuries; (3) analyze the physical risks; (4) identify the causative factors of risk; (5) recommend changes to enhance the sport's safety.


Fracture of the tibial tubercle.

Fracture of the tibial tubercle. Tibial tubercle fractures are uncommon and rarely occur after closure of the proximal tibial epiphysis. A study of 15 such injuries, all unilateral, showed the age range to be from 12 to 16 years. All injuries were sustained during athletic activities or vigorous play. All of the 15 injuries were treated by open reduction and internal fixation, followed by plaster immobilization for approximately 6 weeks. No early complications occurred, and no later deformities, such as genu recurvatum as reported by Blout, were detected. All patients returned to normal activity including in some cases, varsity athletics.


Serum and antral gastrin levels in rats infected with intestinal parasites. Serum and antral gastrin were measured in rats infected with either Trichinella spiralis or Hymenolepis diminuta as a step in testing the hypothesis that parasites change certain aspects of host physiology by altering gastrointestinal (GI) hormone levels or responses to GI hormones. Parasitism with T. spiralis was associated with inflammatory changes in the small bowel mucosa and with a significant increase in serum gastrin. Neither changes in hormone level nor inflammation were induced in tapeworm-infected rats. These results reveal the capacity of tissue penetrating parasites to alter the level of circulating gastrin. This finding coupled with considerable indirect evidence suggests that some of the pathologic changes induced in hosts by enteric parasites may be due to changes in functions that are regulated by GI hormones.


Shock syndrome in primary dengue infections. During 1974, 114 patients with dengue hemorrhagic fever were studied at the Bankok Children's Hospital. Over 40% of the patients had dengue shock syndrome. Five fatal cases were included in the study. Primary dengue infections were identified by absent or low titered antibodies in acute sera and the sequential development of IgM antibodies followed by IgG antibodies during convalescence. Three patients, aged 4,8, and 12 years, had primary dengue infections with shock. Although no convalescent sera could be tested two other patients, aged 7 to 12 years, with fatal disease also appeared to have primary infections. At the time of shock patients with primary infections had subnormal concentrations of complement factor 3. The data show that in older children dengue shock syndrome associated with complement depression can occur during primary as well as secondary infections.


A field trial of competitive displacement of Aedes polynesiensis by Aedes albopictus on a Pacific atoll. Prior laboratory studies and field observations suggested that it might be possible to reduce the size of the population of, or eliminate, Aedes polynesiensis by the introduction of Aedes albopictus. The former mosquito is the principal vector of nonperiodic filariasis caused by Wuchereria bancrofti and the latter is a closely related species refractory to the development of human filariae. The practicability of such competitive displacement was studied by a field trial on a remote coral atoll where there was an established population of A. polynesiensis. Three strains of Al albopictus were liberated at separate localities on the atoll and their fate was followed for 4 years. One strain disappeared within 12 months after release and the other two disappeared within 48 months. It was not clear whether A. albopicuts failed to become established because the strains were unsuitable, the general environment was inappropriate, or A. polynesiensis was present in such numbers that A. albopictus rarely succeded in mating with its own species.


Experimental infection of North American mammals with epidemic Venezuelan encephalitis virus. Eighty-three wild mammals of ten species were inoculated with a first mouse passage level Venezuelan encephalitis (VE) virus isolated from south Texas in 1971 during the VE outbreak. Rodents were highly susceptible to VE infection and circulated VE virus at levels ranging from 10(7.7) to 10(11.5) suckling mouse intracranial lethal doses per ml for 2 to 4 days. These levels of virus could easily infect vector mosquitoes. Mortality was high in all species of rodents except Sigmodon hispidus, adult Neotoma micropus, and adult Peromyscus leucopus. Lagomorphs were susceptible to VE infection but circulated VE virus at or near mosquito threshold levels for 1 day only. Raccoons and opossums were relatively resistant to VE infection or circulated low levels of virus in the blood. Juvenile animals of four species were more susceptible and experienced higher viremias than did adults. In two of the four, mortality was higher in the juveniles than in adults. A consideration of results obtained during this study and those of other investigators led to the conclusion that equines were of major importance, that canines, lagomorphs and rodents were of minor importance, and that other species tested were of no importance as virus amplifiers in VE epizootics.


Treatment for trichuriasis with oxantel. Single doses of oxantel given to 24 children and 37 adults with light to moderate infections of Trichuris trichiura effected cures in 20 of 26 (77%) trials with 10 mg/kg body weight, in 23 of 25 (92%) with 15 mg/kg, and in 10 of 10 trials with 20 mg/kg. In cases not cured, the egg-counts were reduced 50% to 91%. Side effects were not observed, and no drug-associated changes were detected by biochemical, hematologic, and urine examinations before and after treatment.


[Cholinesterases--a group of enzymes important to the anaesthesiologist (author's transl)]. The cholinesterases are two enzymes in the human body which preferably hydrolyze esters of choline. Acetylcholinesterase is structurally bound at the cholinergic synaptic junction being of physiological significance for hydrolyzing the transmitter substance acetylcholine. Pseudocholinesterase is synthesized in the liver and is dissolved in plasma and most body tissues. It has no major physiological function, however, it is of great pharmacological importance since it hydrolyzes suxamethonium. In this paper, the general properties, the mechanism of action, the inhibition by different types of inhibitors and the reactivation of the two enzymes are presented under clinical aspects.


[Ultrastructure of the human lung in shock (author's transl)]. The material investigated was obtained by lung puncture with the aid of the Hausser needle. The puncture technique as well as the preparation of the biopsy material for electronmicroscopic diagnostics are described. The most outstanding criterion in all biopsies examined is the large number of polymorphonuclear, mainly neutrophile granulocytes in the capillary and precapillary arterioles. In contrast, hardly any platelets were found in pulmonary vessels. Also, our investigation of the material revealed no intravascular fibrin deposits while vessels are partly and sometimes completely occluded by fat droplets of different size. The vascular walls are markedly swollen. Fluid escape from smaller vessels results in an edematous swelling of varying degree in the perivascular space combined with fibrin uptake and partly or totally destroyed cell structures. The type I epithelial cells of the lung tissue are swollen and show poor cellular structures. There is in increase of the type II epithelial cells in the shock lung with their lamellary corpuscles partly transferred into the alveolar lumen. The pathomechanisms leading to these changes are discussed. We would like to point out that fibrin was never found intravascularly but was always seen in regions. These findings could indicate increased fibrinolytic activity in shock. Platelet aggregations in smaller vessels are of secondary significance in the material we examined while fat globules, however, play an important part due to their large surface extension. Our electronmicroscopic investigations prove that the lung biopsy method is of great importance for further information on the pathologenesis of early damages in the shock lung not easily discovered by light microscopy.


[Effect of volume substitution with dextran on the haemodynamics under enflurane anaesthesia in geriatric patients (author's transl)]. The haemodynamic effect of enflurane has been examined in two groups of geriatric patients, one with and the other without preanaesthetic administration of 15 mg/kg of 1,8% dextran in lactated Ringer's solution. All the patients have been immobilized for 2 to 3 days before they were operated for an orthopaedic procedure. The administration of the colloidal solution led only to minor cardiovascular alterations: a rise of central venous pressure by 6 +/- 1 (+/- S.E.M.) cm H2O, an increase of mean arterial pressure by 6 +/- 2%, an increase of cardiac output by 10 +/- 4%. Heart rate decreased by 5 +/- 4% and total peripheral resistance by 12 +/- 5%. The cardiovascular depressant effect of enflurance was markedly attenuated by the preanaesthetic volume administration. Mean arterial pressure decreased during anaesthesia by only 16 +/- 3%, as compared with a decrease of 25 +/- 7% in the control group, cardiac output remained virtually unchanged (-3 +/- 9% vs. -37 +/- 5% in the controls) and total peripheral resistance decreased not significantly by 10 +/- 12%, while it rose in the controls by 20 +/- 8%. These findings support the hypothesis that the particular sensitivity of geriatric patients towards the depressant effects of anaesthetics is at least partially due to a compensated hypovolaemia which occurs as a physiological adaptation to immbolization. Enflurane appears as a suitable anaesthetic for geriatric patients, if proper measures for preanaesthetic volume substitution are taken.


[Arvin anticoagulant for prolonged extracorporeal membrane oxygenation (author's transl)]. Treatment of overwhelming but reversible respiratory failure has broadened to include extracorporeal support with a membrane lung. Until recently, it has been necessary to rely on heparin to prevent clotting in an extracorporeal circuit. During prolonged bypass heparinisation may be attended by bleeding. We investigated the use of arvin for systemic anticoagulation in extracorporeal membrane lung bypass in lambs. Arvin is a purified fraction of the venom of the Malayan pit viper. Effective anticoagulation was obtained for an average of 4 days (range 2 to 12 days) through complete fibrinogen depletion by arvin. These preliminary data suggest that arvin anticoagulation may be suitable for prolonged extracorporeal membrane oxygenation.


Postoperative apnoea following nivalin administration. Four patients developed postoperative apnoea after neuroleptanalgesia, and were given Nivalin whilst in an apnoeic state to reverse residual neuromuscular block. Neuromuscular transmission was monitored by a peripheral nerve stimulator, and recurarization was not observed. Central respiratory depression was the cause of postoperative apnoea. The possible mechanisms and the mode of prevention are stated in this paper.


[Post-anaesthetic palsies of brachial plexus (author's transl)]. Six cases of post-anaesthetic upper plexus palsy are described, in one case combined with an injury of the accessory nerve. These palsies are commonly due to stretching of the plexus when the arm is in an extreme position, especially when the neck is extended and flexed to the opposite side at the same time. Though mostly reversible, these lesions can incapacitate the patients for a long period and must be avoided. The methods of prevention are discussed in detail.


[A rare case of tube obstruction (author's transl)]. A case of obstruction of the orotracheal tube following over-inflation of the cuff is reported and a procedure to obtain just sufficient pressure, is described.


[The removal of anaesthetic vapours using t-piece circuits in paediatric anaesthesia (author's transl)]. In order to remove exhaled vapours from T-piece circuits, a rebreathing bag with an additional outlet (double ended bag) may be used. The narrow end of the bag is connected to a circle closed circuit with a filter incorporated in the expiratory side. So T-piece technique remains convenient. A small increase of expiratory resistance of about 1.5-2.5 ml H2O does not change spontaneous ventilation, compared with commonly used semi-closed breathing circuits in pediatric anaesthesia. Assisted or controlled ventilation may be performed, adjusting the expiratory valve at the circle closed system.


[Expiratory air diversion during general anesthesia (author's transl)]. A system for disposing of expiratory air containing volatile anaesthetic gases during anaesthesia is described. It consists of a reservoir bag and an adjustable suction connected to the outlet port of the anaesthesia machine or the nonbreathing valvel. A valve is incorporated which opens to the atmosphere if the reservoir bag should collaps completely, thus creating a slight vacumn in the system. Another valve, opens if the bag should become fully expanded and a slifht positive pressure develop in the system. Halothane concentrations in the "anaesthetists breathing zone" were negligible when this system was being used.


[Blood sugar levels and acid-base balance in babies before, during and after open-heart surgery with hypothermia and extracorporeal circulation (author's transl)]. New borns and babies with congenital heart disease in poor condition have been shown to have a higher risk of developing hypoglycaemia. Blood sugar levels (BSL), acid-base balance and oxygen saturation have been studies in 10 babies from 7.5 to 15 months of age, weighing less than 9kg, before, during and after open-heart surgery. Preoperative mean BSL in the anaesthetized patient was 76mg per cent. It rose slightly after the onset of surgery and further increased to an average of 205mg per cent during cardio-pulmonary bypass with the temperature stablized at 28-29 degrees C. In the early postoperative phase BSL normalized but slowly, reaching a mean value of 107mg per cent 20-24h after the end of surgery. These results demonstrate that, at least under the usual conditions of extracorporeal circulation and hypothermia at our clinic, hypoglycaemia is not a threat in babies undergoing open-heart surgery for total correction of congenital lesions. The possible mechanisms leading to the observed hyperglycaemia are discussed and the results compared with similar studies in adult patients.


[Electrolyte studies in major abdominal surgery. I. Neuroleptanalgesia and Variations of the infusion scheme (author's transl)]. In two groups of 30 patients each who had undergone abdominal surgery under NLA (mean anaesthesia time 4h) we found a small but significant reduction in the serum potassium level after 45 min of anaesthesia. Throughout anaesthesia we found a significant reduction of potassium content of red cells, serum sodium and base excess. Potassium balance shows that under anaesthesia and operation potassium moves out of the extracellular space and the red cells into other compartments. At the same time about 75 per cent of infused sodium and water is retained with a positive correlation between the quantities of sodium infused and retained. A modification of the infusion regimen by substituting glucose solution with distilled water and Ringer lactate with normal saline and 5 mval/l KCI only results in a change in blood glucose and serum sodium.


[Elimination of alkyl phosphates by means of haemoperfusion: experimental results and findings from human casuistics (author's transl)]. We examined the possibility that haemoperfusion with coated activated charcoal might be used in the therapy of alkyl phosphate intoxications. The criterion used was the effect of haemoperfusion on the elimination of alkyl phosphates from the blood. Clearance values for haemoperfusion of nitrostigmine, demeton-S-methyl sulfoxide and dimethoate were determined in vitro. Very good clearance values were ascertained at a blood flow rate of 100ml/min (mitrostigmine 59.20ml/min, demeton-S-methyl sulfoxide 83.70 ml/min, dimethoate 87.84 ml/min). Measurements of the nitrostigmine clearance as a function of various nitrostigmine concentrations in plasma showed that haemoperfusion is effective over a concentration range covering two powers of ten. A 7-h haemoperfusion with coated activated charcoal was performed on a suicide patient with severe nitrostigmine intoxication (Folidol-öl). Clearance values were obtained which were to be expected on the basis of the in vitro investigations. The nitrostigmine concentrations in the extracorporeal blood plasma fell as a result of haemoperfusion to a mid-value of 55 per cent of the initial level. In the patient the level of nitrostigmine in the blood rose showing that there had been a redistribution of nitrostigmine from the tissue or a subsequent absorption from the gastrointestinal tract into the vessels. The results support the use of haemoperfusion with coated activated charcoal in very severe cases of alkyl phosphate intoxication or where standard therapy fails.


[A simple method to produce defined standard gas samples of volatile anaesthetics (author's transl)]. A simple procedure enabling defined (standard) gas concentrations of volatile anaesthetics to be prepared for gas chromatographic analyses in a short time is described. Results obtained with this technique, showing excellent reproducibility (coefficients of variation: 1 per cent or less), are presented. Sources of error inherent in the method theoretically (dilution effect of repeated sampling; not taking into account nonideality of gas mixtures) are discussed, these errors, as easily may be proven, being within the limits of accuracy of the analytical method.


The nuclear fibrous lamina in human cells: studies on its appearance and distribution. The nuclear fibrous lamina, a structure of unknown function, is situated at the nuclear periphery directly apposed to the inner nuclear membrane. Although it has been well described in invertebrate and many non-human vertebrate cells, its occurrence in human tissue has not been emphasized. This survey of a large variety of human cells has documented the lamina to be present, although of varying thickness, in a large number of cell types. It is consistently thickest in mesenchymal or mesenchymally derived cells and its appearance and thickness is not correlated with pathologic alterations.


Electron microscopic stldy of the developing lateral-line organ in the embryo of the newt, Triturus pyrrhogaster. The morphological sequence of events occurring in the development of the lateral-line organ was investigated in the embryo of the newt, Triturus pyrrhogaster, by means of electron microscopy. Six stages of development have been defined for convenience of description. The primordium of the lateral-line organ migrating from the pre- and post-auditory placodes is segmented into a small cell mass accompanied by a few Schwann cells enveloping nerve fibers. In the clump of cells of the lateral-line primordium, three kinds of cells are already distinguished by different degrees of darkness, i.e., dark, light and slightly dark cells (stage I). Both clump and Schwann cells enter the epidermis together (stage II). The two groups of cells are separated by the inner layer of the epidermis (stage III). The organ-forming cells elongate and the inner layer of the epidermis separates the Schwann cells from the clump (stage IV). The apexes of organ-forming cells are exposed out of the epidermis (stage V). The lateral-line organ is almost matured. The dark cells correspond to type II of the supporting cells, the light cells correspond to type I of the supporting cells and the slightly dark cells correspond to the receptor cells because of the existence of cilia and a cuticular plate. The afferent nerve endings are found on the basal surface of the receptor cell (stage VI).


DNA synthesis in the oocyte of the mature mouse: a radioautographic study. Mice were injected three times over an 8-hour period with a total of 48 muci 3H-T/gm of body weight and were sacrificed 1, 3, 5, 9 and 17 days afterwards. Radioautographs of the ovaries showed significantly higher grain counts in oocytes of follicles that are in the antrum formation stage. The radioautographic visualization of DNase digestible 3H-thymidine incorporation into the juxtanucleolar region in oocytes of mature mice occurs in association with ooctye growth in follicles that are in the antrum formation stage. The scheduled disappearance of this juxtanucleolar oocyte DNA and its label during later oocyte growth suggests a degradation or dispersion of this labeled DNA prior to ovulation.


Metabolism of ATP during anoxia in guinea pig seminal vesicle mucosa. The content of adenine nucleotides in guinea pig seminal vesicles was determined enzymatically. Inosine monophosphate (IMP) was isolated from other tissue nucleotides by two-dimensional thin-layer chromatography on cellulose PEI plates, eluted, and quantitated spectrophotometrically. The intracellular concentration of IMP increased 10-fold over control values (aerobic tissue) concomitantly with the strong ATP drain caused by anoxia. This contrasts markedly with other tissues in which ATP depletion is usually associated with an increase in AMP. Tissue inorganic phosphate also accumulated in an amount corresponding to the apparent ATP depletion. Uric acid did not accumulate. Our data suggest the possibility of a special role for IMP in metabolic control in this tissue.


Dose-dependent effects of milk lipids on sex hormone and blood lipid levels in male mice. Diets containing powdered whole milk caused a dose dependent increase in seminal vesicle weights when fed to 21 day old intact male mice. Blood cholesterol levels increased as the lipids in the diet increased. Triglyceride levels were high and inversely related to lipid intake. Peripheral androgen concentrations decreased as the lipid intake and seminal vesicle weights increased, indicating a possible shift of the hormone to the target organ tissue.


Three cases of low chiasma frequency associated with infertility in man. Three new cases of low chiasma frequency in infertile men are described. In the first case, all cells showed abnormal diakineses; in the second, 20% of the diakineses were desynaptic, while the remaining 80% were normal; in the third, all diakineses were desynaptic and showed chromosome fragmentation. The possible mechanisms leading to asynapsis, desynapsis or precocious chiasma terminalization are discussed.


Stages of the cycle of the seminiferous epithelium in the dog. In principle, the spermatogenesis of the dog resembles that of other animals. It consists of 6 consecutive, differentiating spermatogonia generations (A1-A4, Im, B). The number of ensuing spermatogenetic cell generations corresponds to that of other mammals. We divided the spermatogenesis of the dog into 10 stages in order to attain a precise systematization. The cell-divisions of the successive spermatogonia occur in stages II, III, V, VI, VII, and VIII. Stages V a and V c are characterized by the meiotic divisions.


On the brain monoaminergic systems relating to ejaculation. I. Brain dopamine and ejaculation. The effects of psychotropic drugs on ejaculation in dogs and on brain monoamines in dogs and rats were investigated. The results obtained in this study indicate that ejaculation is activated by the dopaminergic system in the brain, and that dopamine in the anterior hypothalamus is closely related to the occurrence of ejaculation.


Sterility induced in male rats by injection of chemical agents into the vas deferens. Changes in the histopathology of the testes with the epididymis were studied 3 months and 6 months after vasocclusion either with ethanol urea mixture or ethanol alone in male rats. A gradual decrease in the fertility of treated animals was observed. The epididymis showed tubules with sperm granuloma and the testis showed empty tubules with Leydig cell hyperplasia in the urea-ethanol treated animals.


[Method of localization and evaluation of DNA quantities in bull spermatozoa]. The author attempted to evaluate the DNA quantities by means of a spectrophotometric method of UV light absorption. In a first publication data have been reported on the RNA quantities obtained by this method. This one concerns the data obtained on DNA. By this method, the manipulations on the spermatozoon are more dimple and sources of error are so discarded. It was so possible to get individual data on each spermatozoon, what is possible with chimical methods which give global quantities for a whole sample of semen. It is moreover possible to delimite the localization of DNA and to measure the amounts in each localization. The scale of the obtained data is large enough for information to several workers. The founded quantities and variations in data will be discussed in a following paper.


Acid phosphatases of the rat epididymis. I. Fractionation and substrate specificity. Three separate acid phosphatases were found in the rat epididymal homogenate after fractionation by DEAE- and CM-cellulose chromatography as well as by electrophoresis. They differed from each other also in substrate specificity. This can possibly be utilized as an aid in their differential quantitation. Some other species including man, dog, rabbit, guinea pig and mouse also had a multiple composition of epididymal acid phosphatases.


[Studies on the reaction of the rabbit testis after ligation of the arteria and vena testicularis compared with ligation of the vein alone]. In surgical treatment of Varicocele compete the ligation of the V. testicularis (Ivanissevich/Bernardi) with the ligation of the A. and V. testicularis (Palomo). Because there are doubts against throttling the arterial blood supply of a previous damaged testis, the effect of ligation of A. and V. testicularis on the testis was studied and compared with the ligation of the vein alone. On 18 adult rabbits either the Palomo operation was performed on one side, leaving the contralateral side as control, or on one side only the vein was ligated and on the other side artery and vein were ligated, permitting, so a direct comparison on the same animal. All the testes were examined histometrically. In the control group the diameter of the tubuli increased from 218 mu after 3 months to 253 mu after 10 months. In the Palomo-group the diameter decreased from 153 mu after 3 months to 82 mu after 6 months, and increased again to 153 mu after 10 months. In the Bernardi-group no differences to the normal testes were found.


Dietetic habits and quality of semen in Indian subjects. Dietetic habits revealed significant effect on seminal plasma vitamin B12 levels. The mean values for seminal plasma vitamin B12 activity in lactovegetarians from normozoospermic, oligozoospermic and azoospermic groups are significantly lower than the corresponding mean values observed in the nonvegetarian subjects. The mean vitamin B12 content of seminal plasma in azoospermic group was distinctly lower than the mean values in normozoospermic and oligozoospermic groups. However, seminal plasma vitamin B12 values showed no correlation with the sperm content of the corresponding semen in both normozoospermic and oligozoospermic subjects. Studies on sperm morphology and on biochemical parameters revealed no significant effect of the type of diet on sperm count, sperm motility, percentage abnormal sperms, seminal plasma total proteins, albumin, fructose, citric acid, acid and alkaline phosphatase activity in normozoospermic group.


[A defect of the head-flagellum-connection of human spermatozoa]. A spermatozoa defect with an obligate heat-flagellum-crack which implies infetility is reported. Hereby the connection of the flagellum with the nucleus is loosened. The axis of the flagellum is displaced from the axis of the nucleus up to 160 degrees. The motility of these spermatozoa is not perceptibly disturbed.


[Reports of clinical cases of taeniasis and consumption of taeniacides in the GDR district of Leipzig from 1967 to 1970]. Ascertainments on notifications of cases of taeniarhynchosis and of the consumption of taenial therapeutics in the regions of the district of Leipzig during the period 1967-1970. The factors are discussed which have influence on notifications or on the consumption of taenial therapeutics. From these examinations resulted, that consumption of taenial therapeutics come near to genuine extensity of the population, but it is not equal to this. The causes, at present, for bad notifications must be found and changes must be introduced. The statistics of numbers on consumption of taenial therapeutics must be improved and the sector of veterinarian science must be excluded.


[Evaluation of mirex for the control of pharaoh's ants]. The paper analyses the mode of action of the organic chlorine compound Mirex in laboratory colonies of the pharaoh's ant Monomorium pharaonis under the special view of practical use in control measures in comparison with the related insecticide Chlordecone (Kepone). Similar to Chlordecone the queens are very susceptible towards the action of Mirex. According to the regression lines of the mortality the best concentrations for practical control measures are in the range of 0.1 to 1%, respectively. Under laboratory conditions a reliable eradication is effected by an application of 0.001% Mirex over a period of three weeks. Such a treatment lead to the loss of reproductive capacity of the remaining living queens. These queens do not recover after transmission to normal colonies. The larvae were influenced in the same manner as the adults. At the recommended level of Mirex all of the larvae disappear within the first five days of application of the poison bait. Also a short termed use lead to a long lasting damage of the ant societies. Between different baits no significant difference could be demonstrated even when one bait obviously was better accepted than another. Because of the strong effect on intact colonies Mirex should be recommended for the control of this ant pest.


[Accidents of fulguration].

[Accidents of fulguration]. Fulguration, first electric accident in which the man was a victim, is to day better known. A clap of thunder is decomposed in two elements: lightning, and thunder. Lightning is caused by an electrical discharge, either within a cloud, or between two clouds, or, above all, between a cloud and the surface of the ground. Experimental equipments owned by the French Electricity Company and by the Atomic Energy Commission, have allowed to photograph lightnings and to measure certain physical characteristics (Intensity variable between 25 to 100 kA, voltage variable between 20 to 1 000 kV). The frequency of storms was learned: the isokeraunic level, in France, is about 20, meaning that thunder is heard twenty days during one year. Man may be stricken by thunder by direct hit, by sudden bursting, by earth current, or through various conductors. The electric charge which reached him may go to the earth directly by contact with the ground or may dissipate in the air through a bony promontory (elbow). The total number of victims, "wounded" or deceased, is not now known by statistics. Death comes by insulation breakdown of one of several anatomic cephalic formations: skull, meninx, brain. Many various lesions may happen in survivors: loss of consciousness, more or less long, sensorial or motion deficiencies. All these signs are momentary and generally reversible. Besides one may observe much more intense lesions on the skin: burns and, over all, characteristic aborescence (skin effect by high frequency current). The heart is protected, contrarily to what happens with industrial electrocution. The curative treatment is merely symptomatic : reanimation, surgery for burns or associated traumatic lesions. A prevention is researched to help the lonely man, in the country or in the mountains in the houses (lightning conductor, Faraday cage), in vehicles (aircraft, cars, ships). The mysterious and unforseeable character of lightning still stays, leaving a door opened for numerous investigations.


[European species of Mallophaga genus Pleurinirmus]. The genus Pleurinirmus ZLOT. has been erected monotypically. In this paper, 4 further species are added. Of these, the following 3 are described as new on the basis of Polish and Finnish material on: P. affectator n. sp. from Sylvia borin, P. phylloscopi n. sp. from Phylloscopus trochilus, and P. rarus n. sp. from Phylloscopus collybita.


[Prevention of phenylephrine-induced acute experimental pulmonary edema in the rat using furosemide]. The intravenous, intraperitoneal or oral administration of furosemide before intravenous infusion of phenylephrin protects rats, the highest doses and the longest the time between administration of the diuretic drug and the beginning of injection, inducing the best protection. The diuretic effects of furosemide do not seem to be the only ones involved because rehydrated animals by isotonic saline solution are still protected. Moreover other diuretic drugs as acetazolamide are useless and on the other hand ethacrynic acid, without any diuretic activity in the Rat, can protect that animal from the edematous effects of phenylephrin.


Haemaglobin and transferrin polymorphism in the Muzaffarnagri breed of sheep and its crosses with Corriedale. Allelic frequencies for haemoglobins and transferrins in the Muzaffarnagri breed of sheep have been reported. All the three haemoglobin types were recorded. Seven transferrin phenotypes, TfAB, TfAD, TfBB, TfBC, TfBD, TfBE and TfDD, were observed. The gene frequencies for TfA, TfB, TfC, TfD and TfE were 0.032, 0.330, 0.001, 0.620 and 0.010, respectively.


Polymorphism of phosphoglucomutase in a German breed cattle. Haemolysates from cattle belonging to the Hochfleckvieh breed (N = 42), were studied for electrophoretic variation of phosphoglucomutase. Three phenotypes were observed which could be explained on the basis of two alleles PGM1A and PGM1B. The PGM1B frequency of 0.7325 is comparatively lower than in other breeds.


Characterization of chicken plasma alkaline phosphatase isozymes by urea and heat treatments. The effects of urea and heat treatments on electrophoretic pattern and activity were investigated in chicken plasma alkaline phosphatase (AP). The B band, which had a slower migrating rate to the F or S band irrespective of isozyme types, was labile to urea (4M) and heat treatments (60 degrees C, 10 min), while the F and S bands were stable to the same treatments. From these results, the genetic control of the three chicken plasma AP isozymes, i.e., F, S and B bands, was discussed. The total AP activity of the F or S type was little affected by urea treatment in spite of the unstableness of the B band. It is considered that the B band inactivated by urea restores the activity when the urea concentration was reduced. The AP activity was reduced by the heat treatment. The reduction may be primarily due to the loss of the activity of the B band.


Sensitivity to odours in the embryo of the domestic fowl. Sensitivity to odours in the embryo of the domestic fowl was investigated on the day before hatching. Embryos were tested with four odorants: dichloroethane, cineole, amyl acetate and formic acid. Three odorants (dichloroethane, formic acid and cineole) produced an increase in the heart rate and a rise in the rates of beak-clapping and the first two increased the amount of head-shaking. Odorants had little effect on other types of activity. The response to amyl acetate varied between experiments. Blocking the nostrils with wax abolished the response. Some implications of these results are discussed briefly.


The social-avoidance behaviour of autistic children. Direct observation and previous studies suggest autistic children actively avoid social encounters more than normal children, and concommitantly, act as if threatened by the mere proximity or non-threatening approaches of others. A study is reported which supports this. The 'cognitive-language handicap' theory of autism is criticized in the light of these results.


[Paracoccidiodomycosis (South American blastomycosis): general review and report of cases]. The author presents and comments upon 19 cases of paracoccidiodomycosis (South American Blastomycosis). He sums up the fundamental epidemiologic and parasitologic aspects of the disease. He points out the diversity of its anatomoclinical features, and underlines the role of the pathologic anatomy in the diagnosis of the disease which necessitates of course an immunologic study. Histology also allows the appreciate the effect of specific treatments and to emphasize the formidable sclerogenic tendency of the disease when the patient has not been long enough under treatment.


[Inflammatory granulomas in the pathology of the nervous system. General remarks]. The "gliogenic" participation in the edification of granulomas may produce peculiar morphological features especially in the central nervous system, and perhaps more than elsewhere, pseudotumoral features. Moreover, the concept of "granuloma" is perhaps not as well defined as in the other tissues. There are also some still unsolved problems concerning the histogenesis of the cells of the "granuloma". Some examples taken among the different etiologies illustrate these notions.


[The different cells forming granulomas: morphologic features, origin, function and development]. Granulomas consist of an aggregation of lymphocytes and of phagocytes (polynuclear and histiomonocytes) around a tissular lesion. The cells are provided by the blood and/or the lymph. Other cells develop in the focus. Within the granuloma appear other cells which derive from the previous ones, viz immunoblasts, plasmocytes, macrophages, epithelioid and giant cells. These elements cooperate to destroy the invading agent. Mastocytes, fibroblasts and myofibroblasts join in. In the granuloma these latter give rise to scarring.


[Resorbing granulomatous process at the contact with the corpuscles of Hassall. Histopathologic aspects]. A histopathologic study of the thymus in human allowed in 14 cases to give evidence of a granulomatous process with macrophages and multinucleate giant cells. These cells are seen at the contact with the corpuscles of Hassall. They dissociate the structure of the latter and contribute to their disappearance. These resorptive granulomatous phenomena illustrate an ill-known aspect of the dynamism of the corpuscles of Hassall.


[Fibroblast and myofibroblast in the granulation tissue]. Review of the literature shows that numerous authors admit the existence during various inflammatory reactions, and especially in granulation and cicatricial tissues, of peculiar connective tissue cells e.g. modified fibroblast or myofibroblast, with intermediate features between a fibroblast and a smooth muscle cell. Some of the physical and structural characteristics of these tissues would depend on these cells. The ultrastructural features of the cells in human and experimental pathology as well as their connection with the extracellular matrix are recalled.


[Plasmatic glycoproteins and granulomatous reaction]. The first evolution phase of the inflammatory granuloma is characterized from biochemical point of view by an overproduction in the liver of some glycoproteins termed glycoproteins of the inflammatory reaction. The author comments the study of these glycoproteins and of the nature of the endogenic factor producing an increase of their plasmatic concentration. He discusses the physiopathologic significance of the overproduction of inflammatory reaction glycoproteins following the development of an experimental granuloma. The lysosomic enzymes of the leukocytes are thought to play an important role.


[Total serum iron-binding capacity: problems posed by the use of commercial control sera]. After recalling the conditions of fixation of iron on human native serum, the authors determined the TIBC on 15 commercial control sera after titration. The transferrin concentration was determined on 13 sera of human origin, by two immunochemical techniques. They were thus able to demonstrate certain sera including a chelator substance other than transferrin, their TIBC depends only on the experimental conditions; such sera are not usable for quality control. Lyophilisation seems to reduce the reactivity of sites of fixation. It is thus necessary to provide a large excess of iron and prolong the duration of contact.


[Familial granulomatous disease: histopathological and histogentic data]. The lesions seen in chronic familial granulomatosis are variable and seen in varied combinations: granulomas, often disseminated, pseudotuberculous lesions, histiocytes with a high content in lipofuscins seen in the liver, lymph nodes, spleen and lungs in particular. These lesions may be explained at least in part by a congenital defect in leucocytes, which is peculiar to this hereditary disease, and which concernes bactericidal functions.


[Continuous flow determination of plasma uric acid by an enzyme method using a sequential autoanalyzer. Combination with glucose determination in the presence of glucose oxidase]. The simultaneous assays of glucose and uric acid in blood plasma use first a specific oxidase, then a peroxidase and the same chromogenic system. The coupling of the two methods on Autoanalyser SMA 12/60 use five reagents, three of which are identical in the two methods.


[Granulomas caused by animal parasites]. Numerous animal parasites, protozoan, metazoan and in particular helminths, may cause a varied range of granulomatous lesions in man. Study of two examples, the leishmaniasis granuloma and the schistomiasis granuloma, would appear to indicate that reactions between the host and the parasite at various stages of its development are dependent upon facilitation or rejection phenomena in which both humoral and cellular mechanisms are involved. The appearance of the granuloma thus depends upon the reactional possibilities of the host. The lesions seen in these granulomas may be related to a certain number of basic processes: phenomenon of necrosis, of fibrosis, specific or non-specific reactions and allergic reactions which are processes also seen under other aetiological circumstances. Certain of them, in particular giant cell or epithelio-giant cell reactions and the tissue eosinophilia associated with helminthic infestations, the role of which is not clearly known, are suggestive of a parasitic aetiology but are in no way pathognomonic. Thee demonstration and identification of the parasite, sometimes difficult or even impossible, should take into account the geographical and epidemiological context, as well as the localisation of the lesions, and often require the pathologist to study serial sections, with special stains. The timely aid of the parasitologist or immunologist is often essential to the aetiological diagnosis of the granuloma.


[Experimental granulomas].

[Experimental granulomas]. The various techniques used for obtaining granulomatous lesions are reviewed, account being taken of the type of animal, the organ, the inducing agent and its mode of administration. The different aspects of the granulomatous lesions are then described with respect to the cell population examined and to the dynamic of the macrophagic behaviour within the lesions, the dynamics making it possible to make a classification according to the rate of renewal of the cell population concerned. Some particular cases are examined, in particular with regard to the interactions of the granuloma with other pathological processes such as bacterial infection or immunitary reactions.


[Automatic determination of urinary mineral phosphate by centrifugation analysis]. Urinary phosphate with acid vanadate and molybdate induces a yellow coloration. The absorbance is proportional to concentration. Kinetics of the reaction including this maximum are measured on Centrifichem; the material and methods, the criteria of validity are presented and discussed.


[Changes in the bone marrow in cancer patients. 61 bone marrow biopsies]. The authors studied 61 bone marrow biopsies carried out in cancerous patients, presumably suffering from a bone metastasis and before any treatment. They feel that quantitative and qualitative changes in the bone marrow may be considered to be an indirect diagnostic indication of metastatic spread.


[Microdetermination to creatinine in biological fluids by kinetic methods. Comparison with continuous flow methods]. The authors compare the performances of two micromethods of determination of creatinine in biological fluids, based on the measurement of the kinetics of the reaction of Jaffe: one was adapted to an analyser of the rate of reaction LKB 8 600, the other, a rapid analyser by centrifugation, the Centrifichem. Correlations with continuous flow techniques with dialysis are also reported.


[Inflammatory granulomas of fungal origin]. This trial on the histopathology of fungal granulomas was aimed at showing that fungi are good models for examination of variations in cellular participation in the inflammatory reactions which they provoke. Their presence stimulates activity of the entire leucocyte series and their tissular differentiations. They clearly demonstrate the association of capture phenomena with the polynuclears and macrophages as well as the humoral phenomena of immunity with the lympho-plasmocytes. Changes in the histiocytes are particularly remarkable in the mycoses and whilst the epithelioid cell found within tuberculoid structures seems, at least in part, to reflect a cutaneous hypersensitivity, the Virchow state corresponds to inhibition of the usual functions of lysis of pathogenic agents, resulting by contrast in undefined, intracellular multiplication of this agent, when cellular immunity cannot develop or has disappeared.


[Histochemical study of the ground substance in chordoma]. Using a series of histochemical reactions, the authors studied the intercellular substance of a chordoma and of one of its recurrences, and were able to demonstrate the presence of neutral substance, of acid mucosubstances with carboxyl groups and sulphated groups. The presence in the intercellular matrix of the chordoma of sialic acid was shown, as well as the probable presence of hyaluronic acid.


[Frequency and significance of intravesicular thyroid crystals]. Using histological examination in polarised light, intravesicular crystals were found in 89 out of 100 thyroids, normal or pathological, removed at autopsy. Crystals were abundant in 44 cases. Pathological changes in the gland result in a irregular and sometimes characteristic distribution of the chrystalline deposits. Intravesicular crystals may reflect local functional variations in the thyroid.


Respiratory effects of live influenza virus vaccine: healthy older subjects and patients with chronic respiratory disease. Twenty-one healthy, middle-aged volunteers and 8 patients with chronic lung disease were given live, attenuated influenza virus vaccine by nasal spray. Forced vital capacity, 1-sec forced expiratory volume, ratio of 1-sec forced expiratory volume to forced vital capacity, residual volume, ratio of airway conductance to lung volume, maximal expiratory flows after exhalation of 50 and of 75 per cent of the forced vital capacity, closing volume, slope of Phase III, volume of isoflow, single-breath diffusing capacity for CO, and arterial blood gases were measured before and 3, 7, 10, and 21 days after exposure. Vaccination was well tolerated by the healthy volunteers without change in pulmonary function. In contrast, the patients tended to develop increased respiratory symptoms and had a slight decrease in mean forced expiratory volume in 1 sec 3 weeks after vaccination.


The value of the skin test and complement fixation test in the diagnosis of chronic pulmonary histoplasmosis. Histoplasmin skin test results in patients with chronic pulmonary histoplasmosis from Missouri and Texas were compared to results in a previous study of U.S. Navy recruits. When consideration was given to geographic areas from which persons from each group were admitted to the study, it was found that the recruits were as likely to have a positive skin test as were those with the disease. In a similar manner, the Texas histoplasmosis patients were compared to groups of patients from that state with chronic obstructive pulmonary disease and with pulmonary tuberculosis. Again, no significant differences were found. It was concluded that the histoplasmin skin test is not of value in the diagnosis of chronic pulmonary histoplasmosis. Histoplasmosis complement fixation test data from the chronic pulmonary histoplasmosis group were compared to data from the chronic obstructive pulmonary disease and pulmonary tuberculosis groups. The usefulness of the complement fixation test in chronic pulmonary histoplasmosis is limited, as with any test, by false-positive and false-negative reactions. A decision theory method was used to define the limits of usefulness.


Five- to seven-year course of pulmonary function in cystic fibrosis. The pulmonary function records of 132 patients with cystic fibrosis followed for 5 to 7 years were reviewed. Changes in forced vital capacity, 1-sec forced expiratory volume, mean forced expiratory flow during the middle half of the forced vital capacity, and 1-sec forced expiratory volume as a percentage of forced vital capacity were examined. There was considerable variation in the rates of change, but the general pattern was consistent with a theory of exponential decline, mean forced expiratory flow during the middle half of the forced vital capacity showing the earliest and most dramatic changes. The pulmonary function of 33 patients (25 per cent) remained stable or improved throughout follow-up, possibly reflecting mild forms of lung disease or the efficacy of therapy. Twenty of these patients (15 per cent) maintained completely normal pulmonary function. The rate of decline in pulmonary function values, with progress of the disease, was steeper in the female patients.


Inhibition of antigen-induced mediator release from guinea pig lung by alcohols. Guinea pig bronchi sensitized to ovalbumin were set up in isolated tissue baths according to the method of Hooker and associates (1,2). In the presence of 10(-6)M atropine, pyrilamine, and indomethacin, concentrations of ovalbumin from 10(-9) to 10(-8) g per ml produced marked contraction of the bronchi. Generally, the antigen-induced contraction could be repeated every 45 to 60 min without tachyphylaxis. Ethanol (1.5 per cent), propanol (0.75 percent), butanol (0.25 per cent), and propylene glycol (1.5 per cent) decreased the contracile response to ovalbumin but either did not influence (ethanol and propylene glycol) or slightly reduced (propanol and butanol) responses of the bronchi to prostaglandin F2alpha. Trachea, bronchi, and parenchyma from sensitized guinea pigs were minced, washed, incubated in Krebs'-bicarbonate solution and challenged with 10(-6) and 10(-4) g per ml ovalbumin. Mediators released into the medium were assayed on unsensitized guinea pig ileum. All the alcohols suppressed mediator release. Circular dichroism demonstrated that the conformational integrity of ovalbumin was not altered by the concentrations of alcohols used in this study. These results show that antigen-induced mediator release is inhibited by alcohols and suggest caution when choosing a solvent for testing the effect of water insoluble anti-asthma compounds.


Effects of shape changes of the chest wall on distribution of inspired gas. The configuration of the chest wall was measured with magnetometers applied at various levels of the rib cage and abdomen. Distribution of ventilation was measured in the supine position using a bolus of xenon-133 inspired at a flow rate of 0.1 liter per sec. Measurements were made during spontaneous breathing, during augmented abdominal breathing, after manual lateral compression of the lower part of the rib cage followed by a predominantly abdominal motion, and after similar compression followed only by increase of the lateral basal rib cage diameter. Basal compression gave a decrease in lateral diameter of 5 to 7 per cent. During spontaneous breathing, apical ventilation exceeded basal ventilation. During an inspiration with an increase of the lateral basal rib cage diameter after compression, the ventilation of basal peripheral regions increased somewhat. No other systematic effects of the changes in either chest wall diameter at the start of inspiration or the type of inspiration were found on distribution of inspired boli.


Mitotic index of the bronchial and alveolar lining of the normal rat lung. Cell turnover in the rat airway epithelium has been studied at 5 levels of the bronchial tree after administration of either colchicine or tritiated thymidine, and in male and female rats of 3 age groups. This is the first study to include all these features of the same species. In the young animals the Mitotic Index (number of cells in division per 1,000 nuclei) decreased progressively to the periphry and was higher in the male than in the female, although the rate of weight gain was the same for both. In the oldest animals no difference was observed between the various airway levels or between the sexes. In the intermediate group the proximal to distal decrease was apparent but the difference with sex was not. The concentration of cells per unit length of airway is higher in the trachea and main bronchus than in intrapulmonary airways. (In the intrapulmonary airways virtually no basal cells are present.) This means that a given Mitotic Index represents replacement of a larger area of epithelium in small airways than in large ones.


Pulmonary aspiration of gastric contents. A retrospective analysis of 50 patients who had been observed to aspirate gastric contents was performed to define better the course of patients with this syndrome. The patients invariably had a disturbance of consciousness, most commonly due to sedative drug overdose or general anesthesia. The onset of clinical signs occurred prompty after aspiration and tended to be similar in all patients, irrespective of their subsequent course or outcome. These findings usually included fever, tachypnea, diffuse rales, and serious hypoxemia. Cough, cyanosis, wheezing, and apnea were each seen in approximately one third of the cases. Apena, shock, and early severe hypoxemia were particularly ominous events. Initial roentgenograms revealed diffuse or localized alveolar infiltrates, which progressed during the next 24 to 36 hours. Subsequent clinical courses followed 3 patterns: 12 per cent of the patients died shortly after aspiration; 62 per cent had rapid clinical and radiologic improvement, with clearing, on average, within 4.5 days; 26 per cent demonstrated rapid improvement, but then had clinical  and radiographic progression associated with recovery of bacterial pathogens from the sputum and a fatal outcome in more than 60 per cent. Treatment from the outset by adrenocortical steroids or antimicrobial agents had no demonstrable effect on the outcome. The clinical features of aspiration of gastric contents are characteristic and distinguish it from other forms of aspiration-related lung disease.


An improved pulmonary angiographic technique using a balloon-tipped catheter. Selective pulmonary angiography, using injection of contrast material distal to occlusion of a lobar or segmental vessel with a balloon-tipped catheter, was performed in 33 patients suspected of having pulmonary embolism. Excellent film quality was possible with this method using specialized radiographic techniques allowing exposure of rapid-sequence spot films. Balloon-occlusion angiography contributed to, or improved on, findings on standard angiograms in 28 of 33 patients; the procedures were inconclusive or incomplete in 5 cases owing to unavoidable technical factors. In general, image quality, definition of both large and small vessels, and visualization of emboli were often superior to results obtained by routine angiography. This technique is safe, relatively easy to perform, and capable of serving as a valuable adjunct to established diagnostic procedures for pulmonary embolism.


Case reports: pleural melioidosis.

Case reports: pleural melioidosis. We report herein a patient with pulmonary melioidosis, whose initial chest roentgenogram revealed only a pleural mass. The patient had not been in a zone endemic for melioidosis during the previous 15 months. We stress the importance of including melioidosis in the differential diagnosis of pleural lesions, and of considering this diagnosis in any patient who has been in an endemic zone at any time in the past.


Antibodies against rifampin in patients with tuberculosis after discontinuation of daily treatment. The presence of antibodies to rifampin was determined in sera of patients with tuberculosis on daily treatment one day after discontinuation of treatment, one week later, 3 weeks later, and 8 weeks later. The highest number of positive patients was found in the third week.


A rapid method of disinfecting the bronchofiberscope. A method of disinfecting the bronchofiberscope that requires 5 minutes was tested against Mycobacterium tuberculosis, Pseudomonas aeruginosa, Serratia marcescens, Klebsiella pneumoniae, Staphylococcus aureus, Candida albicans, influenza virus, and rhinovirus. The bronchofiberscope was contaminated with either sputum or mucin containing the microorganism. Disinfection was performed by washing the inner channel and the outer sheath with a hexachlorophene detergent followed by a solution containing povidone-iodine, ethanol, and water. A total of 76 specimens was tested; all postdisinfection cultures were sterile with the exception of one containing less than 102 colonies per ml of S. aureus.


A comparison between the three largest and three last of five forced expiratory maneuvers in a population study. Five acceptable forced expiratory maneuvers were obtained with a portable spirometer from each person in a population of 1,670 selected from a stratified random sample of a community. The largest 3 of 5 tracings were identifiable as a significantly different subser of the 5 tracings. In 83 per cent of comparisons, the variance of the last 3 was greater than that of the largest 3. Among the largest 3 tracings the highest single value was also identified as significantly different from the other two tracings. For epidemiologic purposes the largest 3 of 5 acceptable tracings is preferable to the last 3 of 5.


["Astasia-abasia," unilateral left-sided apraxia, and touch disorders in an astrocytoma of the corpus callosum. A clinico-pathological report]. The authors report the case of a 55 year old woman suffering from an astrocytoma of the corpus callosum, probably originating in the middle part of the commissure and subsequently involving the whole structure, beyond which it extended very little. They describe the symptoms and signs, consisting initially of a progressive isolated astasia-abasia, in the absence of any psychological disturbance, and subsequently consisting of an apraxic disorganisation involving particularly gestural activity of the left upper limb. They discuss the significance of the psychological disturbances and problems of stasis and walking classically described in relation to tumoural pathology of the corpus callosum, generally attributed to an associated pre-frontal involvement. They review the principal features the "callosal disconnection syndrome" of which their patient constituted an example.


[Hyperparathyroidism caused by a juxtacardiac adenoma]. The authors present a case of parathyroid adenoma in the sinus of Theile, and in this connection review the deep mediastinal localisations of these "secret" adenomas, inaccessible to the classical pre-operative investigations.


[Evaluation of a broncho-pulmonary cancer patient]. A complete check-up is indispensable in patients suffering from broncho-pulmonary cancer, in order to establish a base-line for the lesions, and necessary in order to pose possible surgical indications. It must make use of the clinical examination and various instrumental exploratory methods which must be used with discrimination depending on the benefits which can be expected of them. Clinical examination is essential; it enables analysis of the symptoms and evaluation of the general condition. Investigation of the progressive potential of the cancer is based on the histological study, evaluation of the subject's state of immunity and the time for the tumor to double in size. Functional respiratory investigation is indispensable for any possible surgical discussion. Its importance equals the assessment of local extension of the tumor, of mediastinal glandular involvement and the result of vascular involvement checks. Finally, the identification of metastases remains essential, although deceptive, inspite of progress in the means of investigation which can be used.


[Chemotherapy in primary and metastatic intrathoracic cancer]. Chemotherapy has procured results which are still modest surely valid in the treatment of inoperable primary bronchial cancer: - prolongation of the mean survival time from 3 1/2 months for the nontreated cases to 8 1/2 months for those patients treated with complex combinations; - more than 15% of very good results with return to normal professional activity for 6 to 18 months; - approximately 30% of considerable subjective improvement with a definite sense of "well being"; - considerable reduction in the use of pain-killers. These results amply justify the pursuit of research. 2) The results for the combination hormone-chemotherapy, in the case of thoracic metastases of breast cancer, are definitely better. After leukemia in children, and Hodgking and non-Hodgkin lymphoma, metastases from breast cancer constitute a third group of chemosensitive tumors: - for 64 cases, the percentage of complete or partial remission is 84.3%; - there were 34 complete remissions: mean survival 27 months, at present 11 patients still remain alive: 1 to 16, 1 to 17, 2 to 19, 1 to 23, 31, 35, 38, 43, 68 and 70 months; - 20 partial remissions, mean survival 10 1/2 months, one patient still alive; - 10 failures, mean survival 6 months; - mean duration of complete remission 18 months; - mean duration of partial remission 6 months.


[Nondeficiency chronic polyneuropathies in celiac disease in adults (2 cases with inflammatory neuromuscular vascularitis)]. The neurological and muscular complications seen in coeliac disease in adults are usually attributed to deficiency secondary to malabsorption. Amongst them, however, there exists a very rare cateogory, described by Cooke et al. (1966) taking the form of a chronic myeloneuropathy which cannot be explained in terms of the malabsorption syndrome. Our two cases of gluten intolerance enteropathy, confirmed by biopsy before and after diet, fell into this group of polyneuropathies. The patients, both women, suffered from an essentially sensory ataxic polyneuropathy with accessory motor component with pyramidal and posterior column signs. CSF findings showed a meningeal inflammatory reaction in one of the two cases. These neurological signs, appearing paradoxically during a digestive disease cured by diet, evolve chronically but become stabilised with corticosteroid therapy. Any vitamin deficiency may be excluded in the aetiology of these problems. Neuropathological study of neuromuscular biopsies in very fine serial sections confirmed the mild peripheral nervous involvement but revealed identical inflammatory lesions in the nerve and muscle which were remarkable by virtue of their very highly segmentally selective micro-vasculitis appearance. In these two cases, general, clinical and biological arguments, as well as the type of histological lesion, make it possible to exclude monoclonal gammapathies, malignant haemopathies, amyloidosis and the major collagen diseases. This micro-vasculitis, having transient forms with P.A.N. is no less distinctive, and may be integrated into the provisional group of "allergic angeitis", related to physiopathology of circulating immune complexes and very fashionable in theories as to the mechanism of gluten-sensitive enteropathies. The exact nature of the link between the latter and these types of polyneuropathy remains unknown.


[A proposal of a T.N.M. type of classification of the ear. O.P.A.C. classification of chronic surgical otitis]. With the advent of modern otology, cophosurgeons anxious to compare their results soon became aware of the need for a "T.N.M" type of classification for the ear. The classification described here by the authors is, in principle, a classification of the "T.N.M" type: that is, a purely descriptive classification without prognostic, pathogenetic or therapeutic pretensions. This "O.P.A.C." classification is based on a description of 4 main characteristics: 1) the existence and characteristics of potential otorrhoea, described under the letter C; 2) the characteristics of potential perforation of the tympanum, described under the letter P; 3) the appearance of the middle ear, excluding the ossicular chain, described under the letter A; 4) the condition of the ossicular chain when the surgeon has completed his exploration of the lesions, described under the letter C. Two years experience seems to have proved the convenience and usefulness of this purely clinical classification, providing otologists with a common language. While they are aware of the objections and criticisms to which it may give rise, the authors hope, on time, to improve in this classification.


[Phonation following reconstructive laryngectomy]. The authors describe the results obtained, from the point of view of vocal function in 43 cases of patients who underwent various types of reconstructive laryngectomy: trachio-hyoido-epiglotto-pexy (Arslan and Serafini), crico-hyoido-pexy (Labayle), crico-hyoido-epiglotto-pexy (J.J.Piquet). These operations have as their main aim the preservation of vocal function, for social particularly as it is, increasingly, young people who are affected. The survey was carried out by means of measurement of volume, sonagraph recordings, recordings of movements of the neoglottis by accelerometer and integrating amplification. This method makes it possible to classify voices more objectively. The survey shows the importance of surgical methods and the prime importance of post-operative orthophonic re-education; results have proved very satisfactory three to six months after the operation.


[Electrocochleography in children in Tunisia]. After recalling the technique used for auditory function investigation in children by means of electrochocleography, results are given. These are analysed according to the type of response and its relationship to the site of auditory lesion, that is, there is a description of the type of response obtained in transmission deafness, the nature of the response obtained in perceptive deafness, then some comment is made on some of the types of response which seem to be connected with mixed deafness.


[Our technique of hetero-lateral facio-facial anastomosis by means of nerve autografting in the treatment of permanent peripheral facial paralysis]. The authors describe the technique used in 12 surgical cases of heterolateral facio-facial anastomosis by nerve autograft in the treatment of permanent peripheral facial paralyses. Their main contention is that section of 50 p. 100 of the neurones of the peripheral branches of the facial nerve on the unaffected side does not impair motricity to any extent and that it therefore is possible to anastomose the proximal portion of some healthy branches to the corresponding distal portion of the affected side by placing between them a graft from the external saphenous nerve. The principles for fascicular suture as defined by Seddon and later by Millesi are followed. The technique differs from that made popular by Smith and later by Smii inasmuch as: --the bilateral, hidden face-lift incision makes possible a final passive musculotegumentary suspension of the paralysed side immediately improving the patient's appearance while the nerve re-establishes itself; --retrograde interfascicular dissection on the paralysed side allows precious centimetres to be gained; --pinpointing of the nerve suture area is possible by the placing of a silicone-coated ring with a clip some distance away.


[Assessment of acuteness of hearing using white noise. A comparison with classical audiometry in 357 cases of deafness]. From statistics of 357 cases of deafness it would appear that figures for white noise threshold are practically identical with those for global auditory loss of hearing calculated by means of tonal audiograms according to the usual 5 criteria. Measurement of white noise threshold is a quick and simple method of assessing acuteness of hearing. By bringing into play the whole of the auditory field, it is the equivalent of a real functional investigation of the ear. Furthermore, it is comparable to tonal audiometry in its use of complex sounds but without the disadvantage of relying on intelligibility. In conclusion, the authors suggest a mathematical interpretation to confirm these results.


[Velar tics or pseudo-myoclonus of the palate]. Myoclonus of the palate of neurological origin is now a recognized syndrome. In addition to this permanement neurogenous myoclonus, there are also rhythmical contractions of the velum, usually considered to be psychogenous. A personal case seens to show the existence of a mandibular and tubal factor in the genesis of this false myoclonus. An analysis of cases previously published reveals such factors and these should always be sought as a matter of course. Coorection of them may cause the abnormal movements of the palate, which may constitute a real handicap to disappear.


[Value of the simplified measurement of impedence in perceptive deafness]. After recalling the principles of and the results obtained from the measurement of impedance, the authors discuss the value of this method in perceptive deafness and compare it with the usual tests.


The effect of dextranomer (Debrisan) on hand burns. A preliminary report on a new method in the treatment of hand burns. Dextranomer (Debrisan, Pharmacia, Uppsala, Sweden) is synthetized by cross-linking of dextran chains with epichlorohydrin. It is an insoluble hydrophilic substance which is suitable for topical treatment of secreting wounds, such as burns. Thirteen patients with 17 burned hands were treated. The result of the treatment - decrease in pain, healing time and improved hand function - was registered clinically. No crust was formed. The risk of permanent restriction in range of movements decreased, since the treated hands were soft and mobile throughout the entire period of treatment. All hands treated recovered full mobility. Physiotherapy could be performed daily. No infection appeared because exudate and bacteria were continuously removed from the treated area. Pain rapidly decreased. No side reactions were observed.


A comparative study of three sprayed dressings in healing skin wounds. Three sprayed dressings (Novitas' wound spray, Nobecutan, and Sraycutan) were evaluated as wound covers by using guinea-pigs as experimental animals. There were no statistically significant differences between the closure rates of the wounds covered with the three sprays. All the dressings protected the wounds equally against suppuration, which caused irregular and ugly scars in the non-sprayed control wounds of the same animals. Histologically, the non-treated wounds showed a greater number of leucocytes and oedema than the sprayed ones. This was demonstrable from the 8th to the 16th postoperative hours onwards. There were no histological differences between the variously covered wounds. Histochemically, the most intense enzymatic response to injury was demonstrable in the wounds treated with Novitas' wound spray, followed, in order of decreasing response, by Nobecutan, Spraycutan, and the non-treated wounds. These differences were most marked 4-6 hours after wounding. An intense enzymatic response to injury is considered to be beneficial to the healing process.


Combined trypan blue and formaldehyde-induced fluorescence in experimental skin freezing in the rat. In order to study the effects of skin freezing in the rat on cutaneous vasculature and adrenergic nerves, a combination of trypan blue and formaldehyde-induced catecholamine fluorescence was used. It was shown that trypan blue clearly demonstrates both hyperaemic and ischaemic areas as well as changes in blood cessel permeability after experimental cold injury. Combination of the two fluorescence methods made it possible to correlate rough changes in blood vessel flow and permeability with changes in adrenergic nerves. Twentyfour hours after freezing of the skin, denervation of the most seriously damaged area was apparent. At the border of the cold injury, signs suggesting accumulation of actecholamines were observed in the subcutaneous nerves.


Bone formation with free periosteal grafts in reconstruction of congenital maxillary clefts. In a series of 23 patients free grafts of tibial periosteum have been used in the reconstrlction of 26 congenital maxillary clefts. In 23 (88.5%) of these clefts, rapid bone formation occurred at the transplantation site overbridging the bone defect in 20 (77%) of the clefts. The permanent value of these bone bridges has not yet been solved. Nevertheless, this operation has demonstrated the strong osteogenic capacity of free periosteal grafts suggesting their use also in other fields, where bony fusion or reconstruction of other defects is needed.


Plastic surgery for basal cell carcinoma. A clinical and histopathological study of basal cell carcinomas. During the period 1968-1973 70 patients with 79 basal cell carcinomas were admitted to the Division of Plastic Surgery, Helsinki University Central Hospital. Many of these tumours were primarily treated elsewhere or sent to plastic surgery at the stage when radical surgery was no longer possible. 31 of these primary tumours developed into 70 recurrent tumours. Twelve tumours had highly destructive features. In order to evaluate the frequency of various histological growth patterns in recurring basal cell carcinoma a retrospective study was performed. It became clear that the histological growth pattern was no guide to the rate of recurrence and prognosis. The histological growth pattern of the sclerosing type was found more often in recurrent tumours, possibly a consequence of previous radiotherapy. The incidence of radiotherapy as an initial method of treatment was higher in the group of patients with primary tumours who developed recurrences. Inadequate excision margins were found more often in the same group.


Plasma, red cell and cerebrospinal fluid concentrations of myoinositol in patients with severe chronic renal failure. A study was made of 24 patients with severe chronic renal failure; 14 of them were undergoing regular haemodialysis treatment 3 times weekly. Plasma, red-cell and cerebrospinal fluid concentrations of myoinositol were increased in all the patients treated conservatively. The plasma level of myoinositol correlated with the plasma level of creatinine (r = 0.78). The plasma myoinositol level increased more than the CSF and red-cell levels, indicating that the myoinositol in the red cells and the CSF originated mostly in plasma. Dialysis for eight hours produced a fall of about 50% in the level of myoinositol in plasma while the decrease in red-cell myoinositol was negligible. This lead to an osmotic grandient between extra- and intra-cellular myoinositol which was however small in molar terms and did not correlate with symptoms of central neurological disturbances.


Measurement of cancellous bone strength correlations with mineral density, ageing and disease. A strain-transducer to measure bone strength is presented. Cancellous bone specimens were taken at autopsy from the iliac crests of 28 women and 66 men. There was a good correlation between bone strength, age and bone mineral density. Females had a lower bone strength than males. The bone strength of patients who died of chronic disease known to cause osteoporosis was lower than that of subjects who suffered sudden death. The equipment is also suitable for in vivo studies of human cancellous bone strength.


Screening for breast cancer in women aged 41--60. All women aged 41--60 (20 644) living in the city of Tampere were invited to attend screening for breast cancer during the period April 1974--March 1975. The breasts and the axillary lymph nodes were examined and palpated by specially trained nurses. The women were instructed in self-examination and given a leaflet for study at home. If anything abnormal was revealed at this stage the subject was referred to a physician for further examination. The women who attended totalled 17 261 (84%), 627 (3.6%) of whom were referred for further examination and 615 attended. Surgical biopsy was recommended for 117 (19%) of these 615. Breast cancer was histologically verified in 27 subjects. Ten further cases of breast cancer were detected outside this screening during the same one year screening period, which made the overall detection rate 1.79 per thousand in this age group. As the expected incidence was 1.20 per thousand, the primary detection excess was 0.59 per thousand or 12 cases. A further advantage of screening of this kind is the instruction given to the subjects, which is expected to result in more cases of cancer being revealed at an earlier stage.


Effects of alcohol ingestion on cardiac rhythm in patients with ischaemic heart disease. The effect of alcohol on cardiac rhythm was examined in ten male volunteers with a history of acute myocardial infarction. ECG monitoring with a portable ECG recorder was carried out for a period of 48 hours. After a control period of 15-18 hours an exercise test was performed and repeated after a standard dose (0.5 g/kg b.wt.) of alcohol. Then the patients were allowed to drink alcohol freely for two and half hours. The third exercise test was performed on the second morning. Heart rate at rest and sitting on a bicycle was highest in the third test, during the "hangover" period (p less than 0.05). With a submaximal work load heart rate, and also the heart rate-blood pressure pressure product, were highest after a standard dose of alcohol in the second test (p less than 0.05 and less than 0.01 respectively). The number of ectopic beats showed no significant difference in repeated exercise tests. On tape recordings, however, five of the ten patients experienced changes in cardiac rhythm after alcohol. In two patients the number of ectopic beats increased, the third patient had three successive ventricular ectopic beats after alcohol ingestion and in the fourth patient multiple sinus arrests occurred. In one patient a higher heart rate after alcohol ingestion abolished the ventricular ectopic focus seen during the control period.


Some aspects of phlebographic technique. When contrast medium is infected into an artery it flows to0wards the branches distally to the injectionsite. If, however, the contrast medium is injected into a vein the flow of the contrast medium usually has several routes to strive toward the right atrium. The flow in the veins may be affected by using e.g. compression, Valsalva manouore or gravity. By taking these aspects in the technique into consideration the diagnostic value of the phlebography can in many cases be improved.


Hepatic haem metabolism in porphyria cutanea tarda (PCT): enzymatic studies and their relation to liver ultrastructure. Hepatic levels of cytochrome P-450 are elevated more than 4-fold in porphyria cutanea tarda (PCT) but not in other hepatic porphyrias or in non-porphyrics with alcoholic liver disease. In this study the ability of liver homogenates to metabolise aminopyrine and benzpyrene was correlated with hepatic cytochrome P-450 levels and with liver ultrastructure. The Km and Vmax for aminopyrine-N-demethylation and for benzpyrene hydroxylation exhibited a wide range of values with no significant differences between PCT patients and nonporphyric controls. Proliferation of the hepatic smooth endoplasmic reticulum in PCT was not significantly different from that observed in liver tissue obtained from patients with variegate porphyria or protoporphyria. Kushner reported data suggesting diminished uro'gen-I-decarboxylase activity as the autosomal dominantly inherited metabolic defect in PCT. Red cell uro'gen-I-decarboxylase activity was measured in 5 PCT males and 4 PCT females and activities were compared with 16 sex- and age-matched non-porphyric control patients. There was no significant difference in uro'gen-I-decarboxylase activity in the PCT and non-porphyric patients nor was there any significant difference relating to the sex of the patient. The role of iron in PCT was studied indirectly using the hexachlorobenzene porphyric rat as the rodent model.


The hepatic lesion in protoporphyria (PP): preliminary studies of haem metabolism, liver structure and ultrastructure. Five unrelated patients with protoporphyria (PP) had diagnostic liver biopsies performed to assess the degree of liver damage. The porphyrin content of the liver was quantitated and characterized and liver damage was assessed. Ultraviolet (UV) microscopy was performed in each case. Liver structure was assessed by light, polarization and electron microscopy. In 3 patients the liver was visualized directly before biopsy through a peritoneoscope. Liver damage ranged from minimal cell necrosis to portal fibrosis; the latter was observed in a 27-year-old sib of a patient (M.I.) who had died, aged 29, 3 years previously in liver failure from PP-related cirrhosis. Liver tissue from the latter patient which was obtained at the time of autopsy was re-examined by light and polarization microscopy. Hepatic pigment deposits, thought to be lipofuscin, showed birefringence on polarization microscopy in two cases, one of them being patient M.I. with PP-cirrhosis. Liver fluorescence on UV microscopy was centrizonal, punctate, faded rapidly and was easily distinguishable from that seen in porphyria cutanea tarda (PCT). The porphyrin content of the liver tissue in biopsied patients was between 5 mug and 80 mug, and in the autopsy case 1600 mug protoporphyrin/g wet weight liver, and on thin layer chromatography only dicarboxylic porphyrins were demonstrable. Hepatic cytochrome P-450 levels in protoporphyria were within normal range. Vmax and Km for aminopyrine-N-demethylation and benzpyrene hydroxylation did not differ significantly from our findings in PCT, variegate porphyria in remission and in non-porphyric controls. However, the activity of hepatic delta-aminolaevulinic acid (ALA) synthetase was significantly enhanced in 2 of the 3 patients in whom this measurement was performed.


Red cell uroporphyrinogen I synthetase in acute intermittent porphyria. Uroporphyrinogen I synthetase (URO-S) activity in red cells was measured in 49 patients with acute intermittent porphyria (AIP), in their relatives, in 16 patients with variegate porphyria, and in patients with various forms of anaemia. URO-S activity was clearly lower in patients with AIP (mean 30.5 U, SD 9.7) than in controls (mean 49.5 U, SD 6.4) and in patients with variegate porphyria. There was an overlapping of the values of controls and those of AIP patients, seven patients having fully normal values. Out of 63 relatives eight prepubertal children and two adults with normal urine analysis had URO-S activity below normal. Two newborn infants out of the five studied who had a prophyric parent had lowered URO-S activity in cord blood. URO-S activity was usually elevated in anaemias and correlated to the reticulocyte count. It is concluded that measurement of URO-S activity in red cells is a valuable supplementary method in searching for latent cases of AIP. It is the only method that can disclose the disease before puberty and even neonatally. The major limitation is the occurrence of normal values in some patients with AIP.


Metalloporphyrin contaminations in purified porphyrin preparations as demonstrated by mass spectrometry. Mass spectrometric studies were performed on selected specimens from my collection of over 700 crystalline porphyrin esters prepared over 20 years as well as on similar preparations from other laboratories. Mass spectrometry was performed by J Moller (Department of Chemistry, Odense University) and Elfinn Larsen (Department of Chemistry, The Experimental Division, Risoe, of the Danish Atomic Energy Commission). Nearly all typical crystalline porphyrins contained Cu- and Ni- and minor amounts of Zn- and Fe2-porphyrins, most often above one molar per cent, sometimes 5--10% and occasionally more, up to 35%. There was no close correlation between the metal content and the melting point. A method is proposed for preparation of metal-free ester preparations: Dissolution of either free or esterified porphyrin in conc. H2SO4; mixing of the solution with 19 volumes of methanol; after at least 12 hours adding of 2 vol. CHCl3 and 2 vol. H2O, and washing the CHCl3, phase with 1/2 vol. distilled water until washwater becomes neutral (8--10 times). Preparations made in this way showed below 0.5% metalloporphyrin contamination. The method does not work with protoporphyrin, which is oxidized by conc. H2SO4. The acid extraction leaves some porphyrin partially esterified, which can be removed by preparative TLC. A TLC-method for detection of metalloporphyrin in porphyrin esters is described.


Classification of microcytic anemia by fluorometric analysis of free erythrocyte porphyrins (FEP). Microcytic red blood cells (RBC) occur in iron-deficiency anemia, lead poisoning, and the thalassemia syndromes. Micromeasurement of FEP by acid extraction from RBC was performed on RBC of 64 subjects with RBC mean corpuscular volume less than 78 fl as determined on a Coulter S. FEP was also determined on RBC from 25 nonanemic, normocytic subjects for comparison. The 25 nonanemic subjects, 29 subjects with alpha-thalassemia trait and 16 subjects with beta-thalassemia trait had FEP less than 107 mugm/100 ml RBC. Nineteen microcytic subjects with iron-deficiency anemia had FEP of 185--752 mugm/100 ml RBC. Hemolysates from 8 lead intoxication individuals had FEP values similar to those of iron-deficient patients. The fluorescence emission spectra of lysates with high FEP, which were not extracted, were similar in iron deficiency and lead poisoning. The porphyrin that accumulates in these two conditions appears to be zinc protoporphyrin. Micromeasurement of FEP can be used to initially classify microcytic anemias into either a disturbance of globin synthesis or a disturbance in heme synthesis. Iron-deficiency anemia and lead poisoning cause accumulation of identical prophyrin and cannot be distinguished by fluorometric analysis.


Direct spectrofluorophotometric determination of porphyrin in diluted urine. Direct dilution of freshly passed urine with 19 to 99 volumes of an acid-alcohol solution of chloranil (2, 3, 5, 6-tetrachloro-1, 4-benzoquinone) results in rapid and apparently quantitative conversion of porphyrinogen to fluorescing porphyrin. Dilution must be sufficient to yield an essentially colorless solution. Under these conditions, excitation of fluorescence by 401--405 nm light and fluorescence analysis at 652 nm results in almost complete elimination of quenching and of non-specific fluorescence under the conditions described. Fluorescence intensity is relatively stable for up to several weeks. Alternatively, urine is added to NaHCO3 to permit quantitative conversion of porphyrinogen to porphyrin in 1 to 2 days, and assayed similarly following dilution with the same acid-alcohol diluent (with or without chloranil) or with dilute HCl solution alone. Quantitative results are shown to agree well with those obtained following purification by other, more tedious, procedures. The method has been tested successfully with urines from humans, cows, and rats.


Pharmacological and biochemical properties of kryptopyrrole and its oxidation products possibly related to acute intermittent porphyria. In view of the possible association between clinical symptoms in patients with acute intermittent porphyria and monopyrroles and their oxidation products, a pharmacological investigation was undertaken utilizing mice and rats as the experimental animals to further evaluate this correlation. In mice 4-ethyl-3-hydroxy-3,5-dimethyl-delta4-pyrrolin-2-one was more toxic, and 4-ethyl-5-methoxy-3,5-dimethyl-delta3-pyrrolin-2-one less toxic than kryptopyrrole in the evaluation of behavioural, hypnotic and hypothermic effects. Experiments on the development of tolerance in rats to daily injections of kryptopyrrole have been performed and could serve as a model for the spontaneous recovery occurring in patients with acute porphyria. A new method for the determination of kryptopyrrole in urine is reported. It is based on radiolabelled aldehyde reacting with kryptopyrrole. This method differed from the regular Ehrlich aldehyde reaction, although the results of both methods depend upon dilution of the urine.


Hexachlorobenzene porphyria in rats as a model for human chronic hepatic porphyrias. 1. Hexachlorobenzene porphyria in the rat provides a suitable experimental model of the stages of development of human chronic hepatic porphyria. Just as in chronic hepatic porphyria in man, the development of experimental HCB porphyria in the rat can be divided into several stages. 2. The findings in this study indicate that porphyrins increase in the urine, liver, kidney, and spleen, and to a lesser degree in the serum, with uroporphyrin and heptacarboxylic porphyrin predominating. 3. In contrast to the distribution of porphyrin accumulation in the various organs, clear evidence of a uroporphyrinogen decarboxylase defect was found only in the liver. Formation of uroporphyrin and heptacarboxylic porphyrin by homogenized HCB kidney tissue did not deviate significantly from that by control kidney. The defect could not be unequivocally evaluated in the spleen because the spleen, like the red cells, normally forms considerable amounts of uroporphyrin from porphobilinogen, which were increased only a few times over in synthesis by the HCB spleen. 4. Isomer studies provide no evidence for an additional uroporphyrinogen cosynthase defect.