The pinealocyte--a paraneuron? A review.

The pineal complex develops from a tubular evagination of the diencephalic roof. In amphibians a proliferation zone is the source of the pinealocytes and of the cells of the subcommissural organ. The pinealocytes are not real nerve cells, but derived likewise from the embryonic neural epithelium. The pinealocytes of lower vertebrates are directly photosensitive; however, the morphological structures for direct light perception are gradually lost in the phylogenetic development and are absent in the pinealocytes of mammals. A secretory function is shown in the pinealocytes of all vertebrates, but it is more pronounced in the pinealocytes of reptiles, birds and mammals; dense-cored vesicles originate in the Golgi complex and are transported to and accumulated in the terminals of the basal processes near the perivascular space. Nerve cells are in synaptic ribbon contact with pinealocytes in lower vertebrates and their axons give a rise to the tractus pinealis. The nerve cells and nervous connection with the brain are absent in the pineal organ of mammals. Only few autonomic fibers reach the pineal organ of lower vertebrates, but the sympathetic and parasympathetic innervation are well developed in the pineal organ of most species of birds and mammals. The transmitter release from the sympathetic fibers is influenced by environmental light; light mediates in this way the activity of hormone producing enzymes in the pinealocytes. The synthesis of indolderivates, like melatonin, is confirmed and the presence of a polypeptide hormone is discussed. Accordingly, the pineal organ functions as a "neuro" chemical, "neuro" endocrine transducer or photo-"neuro" endocrine organ, which converts a light input (direct in lower vertebrates, via transmitter release by sympathetic fibers in mammals) into a hormonal output. The pineal organ thus provides the animal with a "biological clock", which is geared to the lighting environment. The pineal organ is a regulator (or a regulator of regulators) for several body functions. In mammals, the influence on the synchronization of the gonadal activity is best known. The pinealocyte is a hormone producing cell, which shows common features with the liquor contacting neurons and with the neurosecretory cells; after the definition of FUJITA (1976) the pinealocyte is said to be a paraneuron, also.


A morphological survey of the median eminence: fluorescence histochemistry, electron microscopy and immunohistochemistry.

This review is a morphological survey of the median eminence of the rat as revealed by fluorescence histochemistry, electron microscopy and immunohistochemistry. Strong catecholamine fluorescence was diffusely distributed in the external layer of the median eminence especially around the primary capillaries of the portal vessels. In the internal layer, there was a scattering of varicosities or strands with catecholamine fluorescence. The origin of these catecholamine nerve fibers and the function of dopamine (DA) nerve fibers in the external layer were discussed. In the external layer of the median eminence, a large number of nerve endings and processes of various sizes ranging from 0.5 to 2.0 micrometer in diameter were found around pericapillary spaces of the hypophyseal portal system. These nerve endings have been classified into three types according to the morphological features of the vesicles contained in them. Small and large dense cored vesicles (40-60 nm, 70-100 nm in diameter) with very high electron density appeared in the first type nerve endings after 5-OHDA treatment; these endings were regarded as monoaminergic, and more specifically, catecholaminergic. Topographical distribution of luteinizing hormone-releasing hormone (LH-RH) nerve fibers in the median eminence was revealed by immunohistochemistry using the peroxidase antiperoxidase (PAP) method. LH-RH nerve processes and terminals appeared as brown beaded strands and dots in the PAP method. LH-RH terminals in the median eminence were seen to be encircling the infundibular radix. However, they were not evenly distributed; the most notable accumulation of LH-RH reactive dots were located in the region extending from the dorsal part of the tuberoinfundibular sulcus to the lateral part of external layer of the superior infundibular labium at the infundibular radix. Considering the distribution of LH-RH, the growth hormone-release inhibiting hormone (GIH) and the monoamine nerve endings in the median eminence, the function of the anterior pituitary appeared to be regulated by a delicate interrelationship of nerve endings.


Exocytosis: the common release mechanism of secretory granules in glandular cells, neurosecretory cells, neurons and paraneurons.

Exocytotic granule release in glandular cells (exocrine and endocrine), neurosecretory cells, neurons and paraneurons was discussed. Attention was focused on the neurosecretory terminals in the mammalian posterior pituitary gland and adrenomedullary cells. The concept of "exocytosis-vesiculation sequence" proposed by Douglas and Nagasawa was introduced. This theory states that the exocytotic release of secretory granules was followed by the mechanism of granule membrane recovery; this process occurred at the bottom of the exocytotic pit in the form of coated microvesicles. Experimental results were presented which substantiated the theory for the transformation of coated microvesicles into smooth microvesicles. The origin and the nature of long enigmatic "synaptic vesicles" in the posterior pituitary gland was thus explained. The exocytotic release probably operates as the general and perhaps sole mechanism of granule release in a variety of glandular cells, neurosecretory cells, neurons and paraneurons.


Adrenal medulla: chromaffin cells as paraneurons.

Adrenal chromaffin cells are typical paraneurons. They are of neural crest origin, secrete catecholamines and produce action potentials. In addition to adrenaline-storing (A) cells and noradrenaline-storing (NA) cells, a third calss of chromaffin cells is distinguishable. They are characterized by the smallness of the secretory granules, and hence are called small-granule chromaffin (SGC) cells. The SGC cells have two or more, long, axon-like processes, receive a heavy innervation, and contain small synaptic-like vesicles in addition to the dense-cored secretory granules of neurosecretory type. Hence, they are regarded as an intermediate form between both A and NA cells of endocrine function and sympathetic nerve cells. Adrenal chromaffin cells share the basic process of the formation, intracellular transport, and storage of the secretory granules with all the paraneurons. Thus, the secretory granules are formed in the Golgi area and contain mainly peptides. They then incorporate adenine nucleotides and catecholamines and when mature are released by exocytosis. By means of autoradiography, quantitative variations were demonstrated with regard to dopa-, dopamine- and noradrenaline-handling capacities within chromaffin cells of a single class. A similar functional differentiation may possibly be found in paraneurons other than the adrenal chromaffin cells. Hypophysectomy in the mouse suppessed the uptake of 3H-dopamine-derived radio-activity in the chromaffin cells. The SGC cells seemed to increase their number in the hypophysectomized mouse.


Some phylogenetical aspects on the occurrence of somatostatin in the gastro-entero pancreatic endocrine system. A histological and immunocytochemical study, combined with quantitative radioimmunological assays of tissue extracts.

Rodioimmunoassayable somatostatin (SRIF) was found in acid ethanol extracts from various parts of the gastro-entero-pancreatic (GEP) endocrine system in reptiles, amphibians, teleost bony fish, cartilaginous fish, and jawless fish, as well as in a deuterostomian invertebrate, the tunicate, Ciona intestinalis. The cellular sites could, as a rule, be easily visualized light-microscopically by the peroxidase-anti-peroxidase (PAP) immunocytochemical procedure, using guinea-pig and rabbit antisera against synthetic SRIF. The standard Hellerström-Hellman technique, used to detect argyrophi SRIF-storing D cells, failed to visualize the SRIF cells in teh GEP endocrine system of the tumicate and of the jaw-less fish. Moreover, the results comfirmed the previous description that this technique only exceptionally (and sometimes only after further modifications) gave positive results when applied to the GEP endocrine system of bony fish, amphibians, and reptiles. In cartilaginous fish, however, it worked adequately and confirmed the radio-immunological and immunocytochemical observations. In the mucosa of the alimentary tract and in the parenchyma of its associated glands of one echinoderm and two pelecypod molluscs and one crustacean arthropod no sgns of the occurrence of SRIF-storing cells were observed using the three correlated procedures. In several of these tissues, signs of the occurrence of insulin-producing cells had perviously been observed. Thus, SRIF seems to appear at a later evolutionary stage than insulin. The principal islets (Brockmann corpusles) of the marine teleost fish, Cottus scorpius, had the highest concentrations of radioimmunoassayable SRIF of all the GEP organs and tissues investigated, viz. about 200 ng/mg wet weight. Nevertheless, it was only 1/5 of the actual insulin content.


Human kidney preservation by flushing with intracellular solution and cold storage.

Simple flushing and cold storage of human kidneys for transplantation has not been accepted for preservation times exceeding 24 hours. A prospective study of 25 primary cadaver kidney transplants was performed to evaluate Collins C2 solution for human kidney preservation. Cold storage time was 10 to 23 hours in 14 cases and 26 to 44.5 hours in 11 cases. Seventeen (68%) of the kidneys had immediate, sustained function. The one-month function rate was 88%. There were no significant differences between the 10- to 23-hour and the 26- to 44.5-hour groups with respect to the incidence of first-week dialysis, one-month graft function, or mean lowest serum creatinine value. Human kidney preservation time can be safely extended beyond 24 hours with Collins C2 flushing followed by simple cold storage.


A review. Lessons from an animal model of intra-abdominal sepsis.

Intra-abdominal sepsis that involves multiple aerobic and anaerobic bacteria derived from the colonic flora was studied in Wistar rats to determine the relative roles of various microbial species. The rats challenged with pooled colonic contents showed a biphasic disease. Initially, there was acute peritonitis, Escherichia coli bacteremia, and high mortality. In rats that survived this acute peritonitis stage, intra-abdominal abscesses developed, and anaerobic bacteria were the preponderant organisms. Subsequent experiments showed that antibiotics directed against coliforms prevented mortality, whereas agents active against anaerobes reduced the incidence of abscesses. Challenges with Escherichia coli alone produced bacteremia and death, whereas pure cultures of Bacteroides fragilis caused intra-abdominal abscesses. These observations suggest that both coliforms and anaerobes are important pathogens in intra-abdominal sepsis, although the different types of microbes appear to play distinctive roles in the sequence of pathological events.


Flail chest syndrome and pulmonary contusion.

Controlled mechanical ventilation has been the mainstay of treatment in the flail chest syndrome for more than 20 years, retrospective studies have recently suggested that the technique is unnecessary, and they infer that spontaneous ventilation or intermittent mandatory ventilation are equally effective. The common theme of these investigations is that mechanical ventilation is required only to relieve hypoxemia associated with the underlying contusion. In two cases of flail chest, spontaneous respiratory efforts resulted in complete disruption of the fracture sites and thus prolonged the duration of mechanical ventilation that was required. In severe cases of flail chest syndrome, there is still a need for controlled mechanical ventilation to splint the rib fractures in a position which facilitates union of the fragments.


Toxicological aspects of food safety - carcinogenicity and mutagenicity.

One major problem in the evaluation of potential carcinogenic food additives and contaminants is that of thresholds or, better, of "no-adverse-effect-levels". Arguments in favour of the postulated "irreversibility" of carcinogenic effects are based on dose-response studies, single-dose and multi-generation experiments as well as on the concept of somatic mutation as the first steps in carcinogenesis with subsequent transmittance of induced defects during cell replication. The problem of extrapolation of results of animal experiments using high doses to low exposure and low incidences in man is not yet solved satisfactorily. Possible practical consequences include zero-tolerance, acceptable thresholds at low risk and safety factors. Acceptable intakes never should be considered constants but should be changeable as soon as new facts in regard to the safety evaluation are available. Several systems of short-term tests as screening methods are based on mutagenicity tests and offer many advantages. Their critical evaluation is of utmost importance. Examples of some relevant problems to be discussed include nitrosamines in food products and their formation from ingested precursors; the migration of vinyl chloride from PVC food packing material; the occurrence of low levels of chloroform in drinking water.


[Roentgeno-morphological study of the 1st metatarsal bone and the calcaneus on the material of archaeological excavations in Latvia].

In the investigation 183 first metatarsi and heel bones of ancient and contemporary people have been examined. It has been stated that the first metatarsi in contemporary people exceed in length those of ancient people. The thickness of substantia compacta of the first metatarsus, as well as the thickness of the tuber calcanei and lamina plantaris of the heel bones was more pronounced in ancient people than in contemporary people. Spongious trabeculae in ancient men were greater in number and thickness.


[Rearrangement of the microcirculatory bed of the skin pedicle flap during the development of complications].

Rearrangement of microcirculatory pathways in the skin was studied without injecting the vessels when the peduncles of a regular size and the peduncles with the ratio of their length to width as 5:1 were formed. In the first case, rearrangement of the microcirculatory bed was revealed to have an adaptive character. In the second case, continuously increasing gross morphological disorders resulting in venous congestion and contributing to necrosis of the peduncle were revealed.


[Proliferative processes in the epithelium of the autotransplant and surrounding skin of mice].

Proliferative processes were studied in epithelial cells of skin autografts and the surrounding skin in mice of CBA line. In the animals subjected to the operation but without cortisone injection (Fig. 1, a and Fig. 2, delta), a high proliferative activity in the skin epithelial cells surrounding the autograft was observed during the whole course of the experiment. In the cells of the autograft, the mitotic activity, after inhibition, restored quickly up to the original level, and in 10 days it sharply increased and did not differ from that in the epithelium of the surrounding skin. The amount of DNA-synthesising cells in the epithlium of the autograft at first remained at the original level, and then, after a short sharp rise, it decreased up to its level in the surrounding skin and then was changing nearly in the similar fashion with it. After repeated injection of cortisone both indices of proliferative activity (Fig 1, delta and Fig. 2, delta) in the epithlium of the autograft and of the surrounding skin gradually increased although slower than in the controls.


[Morphometric evaluation of the intensity of blood flow in the islands of Langerhans and of the effectiveness of controlled revascularization of the pancreas under experimental conditions].

Experiments with 68 white rats have demonstrated that, comparing to the normal, density and area of the pancreatic islets capillaries at alloxan diabetes decreases and is followed by elevation of blood suger and drop in insulin containing erythrocytes. At purposeful revascularization (splenectomy) density and area of capillary surface in the pancreatic islets increases, and diffusion radius decreases, that is accompanied by improved endocrinal function and makes it possible to estimate positively the method of revascularization of the pancreas.


[Effect of different types of sports on skeletal growth in child, adolescent and young sportsmen].

The work represents a theoretical review on the influence of various kinds of sport on the locomotorium. There exists a great discrepancy on how sport influences growth and synostosis in bones. The work from the Department of Normal Anatomy of the First Medical Institute, Leningrad is dedicated to the effects of various kinds of sport on the skeleton of young sportsmen and summarizes the results of the investigations performed. It is demonstrated that different kinds of sport affect differently the process of synostosis in tubular bones. The influence depends on the character of bones involving in the given kind of sport and on the character of physical loading. Thus, the process of synostosis depends not only on genetic factors, but also on social ones which include physical culture. Despite a great number of works dedicated to the study how different kinds of sport influence growth and synostosis of bones, regularities of the process remain to be clarified. Further investigations are needed.


[Neuromorphological and immunofluorescence study of experimental infection caused by the attenuated strain of tick-borne encephalitis virus].

In Syrian hamsters inoculated subcutaneously with an attenuated strain of tick-borne encephalitis virus the infection runs an asymptomatic course in all the animals, some of which, however, develop within 4 weeks some changes in nerve cells and hypertrophy of astrocytes. The viral antigen is detected by Coons' method in nerve cells and spleen cells. An intensive treatment of the hamsters with cyclophosphane 106 days after virus inoculation provoked no morphological lesions in the brain which could have been associated with virus activation. No virus antigen could be found in brain impression smears either. However, in both untreated animals and those treated with the immunosuppressant drug the viral antigen was found in mononuclear cells of the spleen.


[Current problems of pathogenesis of thyrotoxicosis].

According to current concepts, thyrotoxicosis should be regarded as an autoimmune disease in which signs of a delayed type of hypersensitivity are found. The functional excitation of the thyroid gland is caused and maintained by the appearance of lymphocytes sensitized for responding to autoantigens of thyrocytes and for production of thyrostimulating autoantibodies. The course of thyrotoxicosis is aggravated by the disorder of homeostatic mechanisms which normally oppose the hyperfunction of the thyroid gland and the effect of the excess of thyroid hormones. Thus in thyrotoxicosis the disorder of immune homeostasis is accompanied by desorganization of endocrine homeostasis.


[Alkaline phosphatase of striated border of the enterocytes in experimental dysentery].

The activity of alkaline phosphatase of the striated border of enterocytes was studied experimentally in Syrian hamsters in the early stage of adsorption of Shigella zonnei on the epithelium of the small intestine and in a long-term dysentery infection. It was established that upon the direct effect of bacteria on the glycocalix of enterocytes the activity of the enzyme in it at the site of attachment decreased; upon a long-term effect of Shigella on the intestinal wall a decrease in the activity of alkaline phosphatase is systemic.


[Hyaline membrane disease (idiopathic respiratory distress syndrome of newborn infants)].

A review of literature on the morphology and pathogenesis of the disease of hyaline membranes (DHM) in children is presented. The role of predisposing factors in the development of the disease such as inheritance, perinatal asphyxia, prematurity of newborns, diabetes in the mother, Cesarian section, is analyzed. The results of electron microscopic, immunohistochemical and dynamic histological examinations of the lungs in DHM are presented. The current concepts on the association of this disease with a defficiency of a surfactant, alpha1-antitrypsin, hypoperfusion and reduction of fibrinolytic activity of the lung tissue, and with the condition of the vegetative nervous system are discussed.


Antiemetic effect of droperidol after ophthalmic surgery.

Postoperative nausea with emesis is an undesirable side effect of general anesthesia in patients who have undergone ophthalmic surgery. The antiemetic effect of intravenous droperidol (Inapsine) was measured in a double-blind, controlled study of 78 patients undergoing general (enflurane [Ethrane]) anesthesia for a variety of ophthalmic procedures. There was a significant difference in the incidence of postoperative nausea and/or emesis in the droperidol-treated group, 13 of 78 (16%) as compared with the control population (37 of 87 [42%]). No complications of droperidol administration were observed. Droperidol may be an effective antiemetic drug if used prophylactically in patients who receive general anesthesia for ophthalmic surgery.


Indocyanine green: a new vital stain for use before penetrating keratoplasty.

Indocyanine green selectively stains devitalized corneal endothelial cells. In addition, the dye has been found to be nontoxic to the function of living endothelial cells. Indocyanine green appears to be an ideal vital stain for use before penetrating keratoplasty.


Four chest flaps.

A modification of the deltopectoral flap is described, which allows for the use of the anterior oblique chest flap from the same side. The deltopectoral flap is extended laterally over the shoulder, but is modified to extend the inferior incision medially to, but not beyond, the vertical plane of the nipple. This modification does not limit the range of the deltopectoral flap but does allow for development of a second flap that is based on the same four perforating vessels. Two flaps served by the same base provide for four individual chest flaps for use in undelayed reconstruction. A bilobed chest flap can be utilized, undelayed, where the deltopectoral and oblique flaps are raised simultaneously from the same side.


Sinus infection due to Eikenella corrodens.

Eikenella corrodens is a gram-negative rod that has been identified as a cause of endocarditis, osteomyelitis, pneumonia, cellulitis, and other infections. Because it is difficult to grow unless it is incubated in 10% carbon dioxide and because it may be overgrown by other organisms, it can be overlooked as a sinus pathogen. This is a report of the isolation of E corrodens from the sinuses of three patients with sinusitis. Three important features of infection with E corrodens, which are illustrated by these cases, are as follows: (1) the indolence of E corrodens infections; (2) the unusual susceptibility pattern of E corrodens; and (3) the fact that E corrodens is often isolated in mixed culture. The purulent contents of sinus cavities should be cultured in aerobic, anaerobic, and 10% carbon dioxide atmospheres.


The effect of variation in mould temperature, metal temperature and mould size on the development of internal porosity in cast structures.

Three series of two types of specimens were cast from a cobalt and a nickel base alloy using variation in mould and metal temperatures and in mould size. The casting procedures included a unidirectional solidification system and a problem of feeding. Porosity was assessed by radiographic and metallographic analyses.


The effect of variation in the technique of metal fusion on the development of internal porosity in cast structures.

Standard tensile specimens were cast from a series of alloys using several techniques of metal fusion. Subsequently, all specimens were subjected to radiographic and metallographic evaluation inassociation with density determination in order to ascertain the effect of melting technique on the amount and pattern of porosity.


The bonding of polycarboxylate cement to gold.

A comparison is made of several types of treatment of the surface of gold which will promote greater bonding with polycarboxylate cement.


Isolation of bacteriophage-like particles from uninduced Clostridium tetani cultures.

The isolation of hexagonal-headed, tailless, bacteriophage-like particles from uninduced cultures of Clostridium tetani is described. Clear, round, 1--3 mm diameter plaques were noted on Clostrisel agar plates, which were overlaid with soft agar inoculated with 7--14 day broth cultures. Particles were detected by transmission electron microscopy from broth cultures seeded with scrapings from the plaques. Both electron dense and electron lucent heads were noted. An electron dense head was observed attached to the surface of a dividing bacterium.


Haemopoietic stem cells in the foetal mouse thymus.

The presence of haemopoietic stem cells (HSC) in the foetal mouse thymus was assessed to determine whether all cells which enter the developing organ are precommitted to thymocyte differentiation, or if stem cell multipotentiality still exists. The Till and McCulloch spleen colony assay was used to delineate foetal-thymus derived HSC in lethally irradiated recipients. Of the range examined, between 13 days of gestation to birth, a peak of stem cell activity occurs in 15-day foetal thymus. The surface colonies produced by the thymus-derived HSC are small compared to colonies produced by the liver derived HSC, although well within the range of the latter. Histologically, five types of colonies were identifiable which were produced by the thymus-derived HSC, indicating that these cells retain the potential to form a wide range of differentiated colonies.


Evidence implicating the mononuclear phagocytic system of the rat in immunity to infections with Trypanosoma lewisi.

The present study emphasises the importance of the mononuclear phagocytic system of the rat in immunity to infections with Trypanosoma lewisi. Despite the great increase in the weight of the spleen, the liver played a major role in removing the parasites from the circulation. No evidence could be obtained that removal of the parasites was related to the lytic activity of specific antibody and complement.


Battered wives: a controlled study of predisposition.

The possibility that women who are battered by their husband are predisposed to this treatment is examined in a controlled study of 30 such women and 30 control subjects. A number of father-related items distinguished between the two groups: in the battered group fathers had more mental illness, were more violent and tended to be more strict. Battered women more often witnessed violence by their husband to other prior to marriage. All participants were rated for hostility using the Hostility and Direction of Hostility Questionnaire (HDHQ). Both groups emerged as significantly and globally more hostile than a group of normal subjects.


Effect of hyperbaric oxygen on certain growth features of Candida albicans.

Candida albicans (Robin) Berkhout, isolated from an adult female with recurring candidiasis, was tested in vitro for macroscopic and microscopic growth features at varying hyperbaric oxygen levels and at various exposure times and intervals. The organism was found to be inhibited within a pressure/time range well tolerated by human subjects, suggesting that hyperbaric oxygen might be used successfully in treating human candidiasis. Overall experimental results provide an in vitro basis for use of compression chamber therapy in candidiasis treatment.


Protecting chicks and poults from Salmonellae by oral administration of "normal" gut microflora.

Resistance of young chicks and poults to salmonella exposure was substantially increased by early oral administration of intestinal contents or feces from selected adult chickens. Protection was secured also by administering anaerobic broth cultures of intestinal microflora from selected donor birds. Protection, was substantial for 63 days, the longest period tested, although it could be overcome by severe exposure. The protective mechanism appears to be a consequence of competitive exclusion of salmonella by "normal" microflora of the gastrointestinal tract.


Persistent themes: a naturalistic study of personality development in the family.

This pilot longitudinal study of normal children and their families examines the associations noted between behaviors appearing in early childhood and concerns expressed by the same youngster fifteen years later. These concerns were seen to be related to continuing transactions around a particular issue within the family system. A case description of the evolution of the particular patterns of one of the family systems studied and the details of their recurring negotiations includes an examination of two subsystems of the family unit: the mother-infant pair and the parenting couple. The impact of this family system's struggle upon the developing youngster and her personality as a late adolescent is discussed.


Multiple family group therapy: a review of the literature.

This review focuses upon multiple family group therapy, its origin in the intersection of family and group therapies, its use in a variety of settings, its specific techniques and group development in individual and ongoing meetings, its goals and dominant themes, its parallels in family and group work. Also discussed are evaluation of outcome of this therapy modality and those dynamics thought to contribute to family change. Areas for further investigation are outlined.


Migraine and drug absorption.

The majority of migraine attacks are associated with gastrointestinal symptoms which add considerably to the distress and inconvenience caused by the headache. When salicylate absorption from effervescent aspirin tablets was studied during migraine, the rate of absorption was found to be reduced relative to that found in non-migrainous volunteers and in the same patients when headache-free. There is evidence that this reduced rate of absorption is caused by gastrointestinal stasis and reduced rate of gastric emptying. Patients in whom aspirin absorption was delayed were more likely to take longer to respond and to require additional treatment. Metoclopramide, which increases gastric emptying rate, has been shown to improve the rate of absorption of aspirin during migraine and also increase the rate of recovery from the attack and avoid the need for additional treatment; effects which were not shown by thiethylperazine. It is likely that delayed absorption during migraine affects some drugs other than aspirin, such as ergotamine, and it is therefore recommended that the most rapidly absorbable formulation should be used. If such treatment is ineffective, metoclopramide may be a useful addition and should be tried before resorting to other routes of administration.


[Isolation of Haemophilus vaginalis in patients with leukorrhea].

Strains of Haemophilus vaginalis were isolated from patients with leukorrhea. The characteristics of the microorganism that permit its laboratory diagnosis and results of the antibiotic-sensibility tests are described.


[Scalp alopecia in leprosy].

A clinical-pathological study of 270 patients admitted to the "El Rincón" Leprosary is made. The incidence of scalp alopecia, its localization on skull and its association with the polar form of lepromatous leprosy are stressed.


[Microbiological examinations in the intensive surgical care unit of the General Calixto Garcia teaching Hospital].

Microbiological examinations carried out in the intensive surgical-care unit of the "Calixto García" Teaching Hospital between October, 1974 and February, 1976 are exposed. Nineteen examinations were carried out in the unit and results were as follows: 53,1% of the personnel had pathogenic germs (43,8%, coagulase-positive staphylococci; 6,3%, beta-hemolytic streptococci; and 6,3%, Klebsiella). Acceptable results were obtained in the unit air but it was not the case in laboratory and nursery sections. Pathogenic germs found on surfaces and equipments were coagulase-positive staphylococcus, Klebsiella, Aerobacter, Pseudomonas aeruginosa, Citrobacter, Proteus, Escherichia coli and enterococci.


[1st clinical therapeutic trial of mebendazole in some cases of helmenthiasis in Cuba].

Due to the difficulties faced in the etiologic approach of trichuriasis as a result of the intolerance, reduced efficacy and toxicity of some drugs a clinical-therapeutic trial of mebendazole was started in 5-64 year-old patients with some form of helmynthiasis as trichuriasis, enterobiasis or necatoriasis. Coproparasitological examinations carried out 15, 30 and 45 days after the ingestion of the drug depicted an excellent cure rate (98% in trichuriasis; 100% in enterobiasis; and 85% in necatoriasis). Very few side-effects were found. This is the first clinical-therapeutic trial of mebendazole in parasitic diseases in our country, and it can be affirmed that results have been very positive and also that they are similar to those obtained by foreign authors.


[The incidence of Dirofilaria immitis in dogs of Havana City].

The significance of the knowledge of the incidence of Dirofilaria immitis in the dog is emphasized since dirofilariasis is a zoonosis which produce subcutaneous tumors which clinical-etiological diagnosis is very difficult. Adult forms are often located in the skin. The percentage of parasitized dogs found in the Havana city is reported. One-hundred-and-two necropsies of gadder dogs depicted that 6,86% of them had Dirofilaria immitis. Results were negative in the remaining 93,13%.


[Pneumocystis carinii pneumonia].

A study is carried out in 8 infants with a diagnosis of Pneumocystis carinii pneumonia which was established through the study of histologic lung sections, and a microscopic study of protozoas. The following are some of the factors predisposing to this disease: prematurity, significant denutrition, primary immunodeficiencies, extended use of antibiotics, malignancies, and immunosuppressive treatments.


[Indirect parasitological methods. A modification of Baermann's test].

Feces specimens from 483 patients are studied using a modification of Baermann's technique (Gálvez). Comparison is made with other methods. Results obtained have a higher positiveness: in larvae, protozoan, and helminth eggs.


[1st case of human hepatic hydatidosis in Costa Rica].

About seven cases of unilocular hydatidosis for Echinococcus granulosus in porcine and bovine cattles have been found in Costa Rica. According to one out of the authors--Brenes, R. R.--the experimental infection of a dog (1950) after the oral administration of a fertile cyst for obtaining or developing the adult form failed to produce good results. Up to date, no report of the finding of E. granulosus in dogs or in people has been obtained. No additional case of bovine hydatidosis has been reported in Costa Rica in the last twenty years. A patient with hepatic hydatidosis who underwent surgery is presented.


[Etiology of acute diarrheal diseases].

The microbiologic, clinical and epidemiologic aspects of the main biologic agents producing acute diarrheic diseases are reviewed. Some considerations related to the origin of these affections are presented.


[Various considerations on the lesions and treatment of Trichophyton verrucosum in calves. Preliminary report].

This paper is devoted to study the magnitude of the skin lesions produced by Trichophyton verrucosum--previously identified--as well as the therapeutic measures taken. For this study were used 45 calves with a skin fungal process identified, by the adequate culture means, as from T. verrucosum. Through the histic study of the skin biopsy were found several lesions due to tinea corporis dermatitis. The use of the drug employed is described. The cure rate obtained with this drug was the following: an 80% cure within 6 days, a 12,5% within 8 days, and a 7,5% within 10 days; no cure was observed in the controls--5 from the total number.


[Toxoplasmosis and contact with animals: study of 390 cases].

Three hundred and ninety patients with suspected toxoplasmosis due to their contact with animales--they owned them, or work with them--are studied. The great significance of this way of acquiring the disease is stated. Every patient had a complement fixation test and an intradermal reaction test with toxoplasmine. An 85.2% positiveness to complement fixation, and a 64.1% to intradermal test were found among those patients who informed animal contact; a 70,6% positiveness to complement fixation, and a 56,2% to intradermal reaction was found in the patients who denied having any contact with animals. This showed both the importance of animal contact as well as other forms of transmission. The contacts were also studied, and the animals were classified according to J. Jira, the researcher: maximal, high, minimal and unreceptiveness to toxoplasma. The possibility of acquiring toxoplasmosis from other sources besides the close contact with animals must be taken into consideration.


[Obtaining of serum (antibodies) of antitrophozoites of Giardia lamblia and non-specific factors. A practical method].

According to some authors, the nonspecific elements belong to Candida albicans morphologic variables, and according to others, they represent an evolutive stage or are the result of Giardia lamblia. An immunitary methodology is developed in experimental animals combining intramuscular, intravascular and intraperitoneal pathways with soluble substances and extracts which can be absorbed in aluminium hydroxide of Giardia lamblia and nonspecific elements trophocytes. Sera (antibodies) to these organisms are obtained.


Control of intermittent positive pressure breathing (IPPB) by extracorporeal removal of carbon dioxide.

Five lambs were anaesthetized, paralysed, mechanically ventilated and connected to a membrane "lung" to permit removal of carbon dioxide. When part of the carbon dioxide was removed in this manner, the tidal volume was decreased to keep PaCO2 constant. For example, when 70% of carbon dioxide was removed by the membrane lung, total ventilation was reduced by 50%, peak inspiratory pressure was decreased by 45%, and PaO2 was kept constant by increasing the inspired oxygen fraction from 0.21 to 0.27%. The removal of carbon dioxide by a membrane during positive pressure breathing could decrease barotrauma, particularly in poorly compliant lungs. Technically, the extracorporeal removal of carbon dioxide is relatively simple procedure.


A history of nitrous oxide and oxygen anaesthesia IVE: Henry Hill Hickman in his time.

More evidence is presented: a questionable letter from a grateful patient; Hickman's stewardship at a Charity Ball; the baptism of his children at Shifnal. The identities of "John" and "Glover", mentioned in Hickman's letter from Paris, and the marriage of one of Hickman's cousins to the son of a French emigré, are discussed. A recorded gift places Eliza in Paris with Henry on November 10, 1828. The need to assess the evidence in the context of its time and place is stressed.


A possible combination of hypoxic cell sensitizer with an oxic protector: implications for radiotherapy.

This paper discusses the results of experiments using γ-rays and a hypoxic sensitizer metronidazole (MET) and also a well-known protector, mercaptoethylamine (MEA), individually and in combination, on the survival of the yeast S. cerevisiae BZ 34. MET (5mM) gave a hypoxic enhancement ratio (ER) of 1·3. MEA (5mM, 10mM) gave a dose-modifying factor (DMF) of 1·9 and 2·3 respectively for euoxic cells. However, the DMFs for hypoxic cells were 1·0 and 1·1 for 5 and 10mM concentrations of MEA. A combination of 5mM MEA and 5mM MET gave a DMF of 2·0 for euoxic cells and the ER remained at 1·3 for hypoxic cells. The "effective" oxygen enhancement ratios were 2·3 and 1·7 for the control and the sensitizer respectively. In the combination this value was equal to or even slightly less than 1. All DMF, ER and OER values were derived from D(0) values of the survival curves. The values based on 10% survival are almost equal to those derived from D(0) values. All the survival curves gave the same extrapolation number, showing that the chemicals individually or in combination were truly dose-modifying.These results indicate that protectors such as MEA could be preferentially protecting euoxic cells, and that combining such "oxic protectors" with a hypoxic sensitizer could result in protecting euoxic cells while the sensitization of hypoxic cells was not much reduced. The implications of our results for radiotherapy are discussed. It appears that the use of nontoxic oxic protectors may be a useful adjuvant in overcoming the hypoxic-cell problem in radiotherapy.


Radiosensitization of Serratia marcescens by nitropyridinium compounds.

The two nitropyridinium compounds tested sensitize hypoxic Serratia marcescens to irradiation up to the oxygen enhancement level by two components which can be separated as  a function of compound concentration. Sensitization above the initial plateau level is in order of their determined one-electron reduction potentials, Ro 03-5580 (E 7 1 = -335 mV) being more efficient than Ro 03-5637 (E 7 1 = -358 mV). Additivity in sensitization up to a maximum enhancement level of 2.1 +/- 0.1 is found on combining these hydrophilic compounds at concentrations to give sensitization at the plateau level, with the hydrophobic sensitizer paranitroacetophenone (PNAP). It is concluded that the nitropyridinium compounds and PNAP sensitize the same site.


An evaluation of 6 short-term tests for detecting organic chemical carcinogens.

A number of tests have been described which are thought to be capable of identifying carcinogens without using the actual induction of cancer as an endpoint. This study compared the performance of 6 such tests on a selection of 120 organic chemicals. The tests studies were: (1) mutation of Salmonella typhimurium; (2) cell transformation; (3) degranulation of endoplasmic reticulum; (4) sebaceous gland suppression; (5) tetrazolium reduction and (6) subcutaneous implant. A further 4 tests were examined briefly, but were not included in the complete evaluation. The chemicals were classified into carcinogens (58) and non-carcinogens (62) on the basis of published experimental data, and into 1 of 4 broad chemical classes. There was considerable variation between tests in their ability to predict carcinogenicity, with the cell-transformation test and the bacterial-mutation test being the most accurate (94% and 93% accurate respectively). These 2 tests were considered to be of general use in screening, since they were clearly more accurate than the others. Statistical consideration of various combinations of these tests showed that the use of cell transformation and bacterial mutation together, provide an advantage over the use of either test alone. The inclusion of the other 4 tests in a screening battery predictably resulted in a great increase in overall inaccuracy and loss of discrimination, even though the detection of carcinogens is improved. All the tests were shown to generate both false positive and false negative results, a situation which may be controlled by the use, where possible, of appropriate chemical-class controls, to identify the test which is optimal for the class of chemical under test. Structural analogy may have a part to play in the rapid detection of environmental carcinogens, and some general guidelines for its use are given.


Sensitization of ultraviolet radiation damage in bacteria and mammalian cells.

Bacteria (Serratia marcescens) and mammalian cell (Chinese hamster V79-379A) were irradiated in monolayers with ultraviolet light at 254 nm or 365 nm in the presence or absence of radiosensitizing drugs. At 254 nm, killing is very efficient (D37 approximately 1 J m-2 exposure, or  approximately 6 x 10(4) photons absorbed by DNA per bacterium), and sensitizers have no effect. At 365 nm, cells are not killed in buffer, but are inactivated in the presence of nifurpipone or misonidazole. Lethal exposures (approximately 5 x 10(3) J m-2 at 10micrometer misonidazole) correspond to about 10 (7) photons absorbed by sensitizer molecules per bacterium. Toxicity of stabel photoproducts of the drugs is not involved, nor is oxygen required. Hence the transient species formed by photo-excitation of radiosensitizer molecules are capable of killing cells in the absence of other types of radiation damage.


Activation of radiosensitizers by hypoxic cells.

Hypoxic cells can metabolize nitroheterocyclic compounds to produce toxic intermediates capable of affecting the survival of neighbouring oxygenated cells. Mutagenesis experiments with E. coli WP-2 343 (deficient in nitroreductase) indicated that reduction of nitroheterocyclics outside bacteria causes killing and mutations within bacteria, presumably due to the transfer of the "active" specie (s). Using animal tissue slices to reduce nitrofurans, cultured L-929 cells incubated under aerobic conditions were far more sensitive to the toxic and DNA damaging effects of these drugs. Transfer of the active species also occurs in a tissue-like environment in multicell spheroids where the presence of a hypoxic central core served to convert the nitroheterocyclics to intermediates which also damaged the neighbouring oxygenated cells.


Metronidazole (flagyl) and misonidazole (Ro-07-0582): reduction by facultative anaerobes and cytotoxic action on hypoxic bacteria and mammalian cells in vivo.

The toxic actions of the "nitro" radiosensitizers, metronidazole and misonidazole on the bacteria E. coli B/r and Serratia marcescens have been investigated under anareobic and aerobic conditions. The rates of reduction of the drugs by suspensions of these bacteria as well as by suspensions microorganisms from the rat caecum have been measured. Both drugs were reduced or were toxic only under anaerobic conditions. In all instances misonidazole was reduced more rapidly than metronidazole but metronidazole was more toxic. It is suggested that these phenomena may model those occurring with hypoxic mammalian cells in vivo and that care should be taken before automatically extrapolating in vitro data to the in vivo situation.


A fast kinetics study of the modes of action of some different radiosensitizers in bacteria.

Using a fast mixing a irradiation technique, the gas explosion method, with Serratia marcescents, the decay of oxygen-dependent damage is found to consist of a fast and a slow stage, each of which is associated with a sub-component of this damage. In the present work, the interactions of these components with radiosensitizers are examined. At low concentrations O2, TAN (a nitroxyl) and misonidazole all preferentially sensitize the slow-stage damage. At higher concentrations, O2 and TAN sensitize the fast-stage damage by a fixation reaction that competes with its repair; in contrast, misonidazole appears mainly to operate by reaction with an earlier, ever shorter form of oxygen-dependent damage.


Hypoxic cell radiosensitization by 8-methoxypsoralen.

8-Methoxypsoralen has been shown to act as a radiosensitizer of hypoxic bacteriophage and bacteria. Radiosensitization of bacteriophage requires irradiation in the presence of excess scavenger. Bacterial radiosensitization requires deficiencies in uvr and rec genes. For the drug to be effective it must be present during irradiation. Pulse radiolysis studies have shown that, like electron-affinic radiosensitizers, 8MOP can efficiently oxidize free radicals. Unlike oxygen and most electron-affinic radiosensitizers 8MOP does not act in a purely dose-modifying fashion, and can radiosensitize beyond the oxygen effect.


Escherichia coli infection in mice and impaired fetal development.

Investigations were undertaken, using the mouse as an animal model, to study the effect of Escherichia coli on fetal development. The i.v. injection of 7.5 X 10(6) bacteria, originally obtained from a suspected case of human pyelonephritis, caused only a mild and transient disturbance of maternal health but caused severe fetal wastage. Groups of mice were examined 4, 7 and 11 days after infection and the numbers of organisms were determined in the spleen, liver, kidneys, placentas and resorptions. From the findings obtained, it was concluded that the Esch. coli grew preferentially in the placentas. By the 7th day the placentas showed marked degenerative and necrotic changes and the bacteria could be recovered from the majority of fetuses at this time. Histologically, no significant changes were seen in the spleen, liver and kidneys. As a result of these findings in an animal model, and taking into consideration the observations of other workers, it is suggested that coliform bacteraemia in human pregnancies may also cause infections of the placenta and bring about abortion or premature delivery.


Pemphigoid and pemphigus antigens in cultured epidermal cells.

Fractions of IgG from sera of patients with pemphigoid and pemphigus added to monolayer cultures of mouse epidermal cells resulted in a sparse distribution of cells. Direct immunofluorescence studies of these monolayers revealed epidermal cell surface antigens reacting with pemphigoid and pemphigus antibodies. We suggest that these antibodies may bind to epidermal cell surface antigenic molecules which are important in maintaining epidermal cell adhesion in culture.


A simple immunofluorescence test for the detection of platelet antibodies.

Immunofluorescence tests on platelets have always been hampered by nonspecific fluorescence caused by non-immunological binding of plasma proteins to the platelet membrane. It was found that this could be easily overcome by fixation of the cells with paraformaldehyde (PFA). By using PFA-fixed platelets, a simple method for the detection of platelet antibodies, the platelet suspension immunofluorescence test (PSIFT) was developed. PFA fixation did not alter or inactivate the platelet antigens tested. Platelet-reactive antibodies detected specifically with the PSIFT included platelet-specific agglutinins of the IgM class, non-agglutinating platelet-specific antibodies of the IgG class, drug-dependent platelet antibodies, HLA antibodies, as well as anti-A and anti-B antibodies. The sensitivity of the new test was satisfactory, as was its reproducibility. Measurement of platelet immunofluorescence was possible in a continuous flow microfluorometer, making a principle, quantitation of platelet antibodies and antigens possible.


Immune complexes in myelofibrosis: a possible guide to management.

Using a fluorescent technique intracellular immune complexes were found in the peripheral leucocytes in all of 12 patients with myelofibrosis studied. Fluorescent cells varied from 12% to 81%; with no relation to the total white count or any obvious clinical finding. Three of the patients with severe refractory anaemia benefited from immunosuppressive therapy.


Group B streptococcal infection in a maternity unit.

Neonatal infection due to Group B streptococci is described in a maternity unit. Six babies were affected and two died. Three of the babies were born at term, and weighed more than 2.5 kg. Tachypnoea was the earliest clinical sign in each case, and we suggest that newborn infants with persistent tachypnoea and evidence of maternal or infant colonization with Group B streptococci should receive antibiotics. Alternative approaches to the diagnosis and management of infection with Group B streptococci are discussed and rejected.


Photochemical cross-linking of unmodified acetylvalyl-tRNA to 16S RNA at the ribosomal P site.

Acetylvalyl-, acetylphenylalanyl-, and formylmethionyl-tRNA which were derivatized at their 4-thiouridine residues with the photoaffinity label, p-azidophenacyl bromide, were nonenzymatically bound to salt-washed ribosomes. More than 90% of the binding was to the P site as judged by reactivity with puromycin. Subsequent irradiation (greater than 310 nm) of the tRNA-ribosome complexes resulted in the covalent linking of only the acetylvalyl-tRNA to the 30S subunit. Attachment was solely to the 16S RNA with an efficiency of cross-linking of 13--15%. Covalent linking was 90% inhibited by prior treatment with puromycin, showing that the covalent linking reaction had taken place at the P site. Cross-linking required irradiation and mRNA but was not dependent on the presence of the photoaffinity probe in the tRNA. tRNAs whose 4-thiouridine had been modified with unreactive analogues of p-azidophenacyl bromide or unmodified acetylvalyl-tRNA exhibited the same cross-linking behavior as photoaffinity probe-modified acetylvalyl-tRNA. Furthermore, even acetylvalyl-tRNA whose 4-thiouridine had been removed by treatment with H2O2 was quantitatively as active as unmodified tRNA. These results provide the first demonstration of direct photochemical cross-linking of tRNA to ribosomes.


Initiation of enzymatic DNA synthesis by yeast RNA polymerase I.

In vitro DNA synthesis by yeast DNA polymerase I can be initiated by partially purified yeast RNA polymerases in the presence or absence of rNTPs. Homogeneous yeast RNA polymerase I initiates DNA synthesis by yeast DNA polymerase I on single-stranded DNA templates only in the presence of all four rNTPs. A protein capable of initiating enzymatic DNA synthesis on single-stranded DNA in the absence of rNTPs has also been separated from partially purified yeast RNA polymerase I fractions. Analysis of the RNA polymerase I initiated replication products of phage fd DNA on alkaline sucrose gradients showed noncovalent linkage between the newly synthesized DNA and the template. Isopycnic analyses of the ribonucleotide initiated fd DNA replication products demonstrated covalent linkage between the initiator RNA and newly synthesized DNA. Results from 32P-transfer experiments confirmed the covalent linkage between RNA and DNA chains and showed the presence of all four ribo- and deoxyribonucleotides at the RNA--DNA junctions. The ribonucleotide found most frequently at the RNA--DNA junction is uridylate and the purine deoxynucleotides occur more frequently than pyrimidine deoxynucleotides.


Replication of antibiotic resistance plasmid R6K DNA in vitro.

A soluble extract prepared from cells of an Escherichia coli strain carrying the antibiotic resistance plasmid R6K is capable of carrying out the complete process of R6K DNA replication. DNA synthesis in vitro is dependent on the four deoxyribo- and ribonucleotide triphosphates and is sensitive to rifampin and streptolydigin, inhibitors of DNA-dependent RNA polymerase. The incorporation of deoxyribonucleotides into R6K DNA also is sensitive to actinomycin D, novobiocin, arabinofuranosyl-CTP, and N-ethylmaleimide. Kinetics of synthesis are linear for 60 to 120 min. Replication proceeds semiconservatively and supercoiled closed-circular DNA molecules are synthesized. Analysis by alkaline sucrose gradient centrifugation indicated that the early R6K DNA products contain DNA fragments of approximately 18 S in size, corresponding to the length between the R6K alpha origin of replication and the terminus of replication observed in vivo. Addition of exogenous supercoiled R6K DNA is inhibitory to the in vitro system, whereas the addition of R6K DNA in the form of relaxation complex stimulates R6K DNA synthesis to a small extent.


Antibody nucleic acid complexes. Immunospecific retention of N6-methyladenosine-containing transfer ribonucleic acid.

Antibodies specific for N6-methyladenosine (m6A) were immobilized on Sepharose and the resulting immunoadsorbent was tested for its ability to retain those Escherichia coli tRNAs containing the antigenic hapten, i.e., m6A. Results obtained with [32P]PO4- and [methyl-3H]-methionine-labeled tRNAs indicated that approximately 3 to 5% of the radioactive RNA was retained by the immunoadsorbent. Under identical conditions, but in the presence of m6A (1 mg/mL), less than 0.2% of the radioactivity was retained. Subsequent characterization of the retained tRNA via (a) analysis of methyl-3H-labeled, methylated nucleosides, (b) two-dimensional gel electrophoresis, and (c) analysis of the retention of [3H]aminoacyl-tRNA species led to the conclusion that the anti-m6A/Sepharose adsorbent quantitatively and exclusively retained a single tRNA species containing m6A, namely, tRNAVal.


Mechanism of the stereospectific irreversible inhibition of bacterial glutamic acid decarboxylase by (R)-(--)-4-aminohex-5-ynoic acid, an analogue of 4-aminobutyric acid.

4-Aminohex-5-ynoic acid inhibits bacterial glutamic acid decarboxylase in a time-dependent irreversible manner. The inhibition is stereospecific and requires the abstraction of the propargylic hydrogen from 4(R)-(--)-4-aminohex-5-ynoic acid. This leads to the generation of a reactive alkylating agent in the active site which can react with a nucleophilic residue. At complete inhibition, there is incorporation of one molecule of inhibitor per pyridoxal binding site. If the decarboxylation of glutamate occurs with retention of configuration, the irreversible inhibition of this enzyme by the 4-(R) isomer can be rationalized on the basis of reversibility of the protonation step in the normal catalytic mechanism.


Role of arginyl residues in yeast hexokinase PII.

Yeast hexokinase PII is rapidly inactivated (assayed at pH 8.0) by either butanedione in borate buffer or phenylglyoxal, reagents which are highly selective for the modification of arginyl residues. MgATP alone offers no protection against inactivation, consistent with low affinity of hexokinase for this nucleotide in the absence of sugar. Glucose provides slight protection against inactivation, while the combined presence of glucose and MgATP gives significant protection, suggesting that modified arginyl residues may lie at the active site, possibly serving to bind the anionic polyphosphate of the nucleotide in the ternary enzyme:sugar:nucleotide complex. Extrapolation to complete inactivation suggests that inactivation by butanedione correlates with the modification of 4.2 arginyl residues per subunit, and complete protection against inactivation by the combined presence of glucose and MgATP correlates with the protection of 2 to 3 arginyl residues per subunit. When the modified enzyme is assayed at pH 6.5, significant activity remains. However, modification by butanedione in borate buffer abolishes the burst-type slow transient process, observed when the enzyme is assayed at pH 6.5, to such an extent that after extensive modification the kinetic assays are characterized by a lag-type slow transient process. But even after extensive modification, hexokinase PII still demonstrates negative cooperativity with MgATP and is still strongly activated by citrate when assayed at pH 6.5.


A calcium-activated potassium channel present in foetal red cells of the sheep but absent from reticulocytes and mature red cells.

Red cells of adult sheep, like those of other ruminants, lack the calcium-activated potassium channel which is present in the membrane of human red cells. Since the activities of other transport systems in the sheep red cell are known to decrease during maturation of the cell or during development of the animal it was investigated whether the K+ channel is present in red cells from younger animals or in reticulocytes. Using the divalent cation ionophore A23187 to increase the intracellular Ca of intact cells, it was found that the K+-selective channel is present in foetal red cells from the foetus or newborn animal but not in reticulocytes. The presence of the channel showed no dependence on the K+ genotype of the sheep and was not associated with either "high K+"- or "low K+"-type Na+ pump. No Ca2+-dependent change in K+ permeability was found in red cells from either newborn or adult donkeys suggesting that its presence in the red cells of the foetus may not be general. The role of the K+ channel in the mammalian red cell and the relationship between the K+ channel and the Na+ pump are discussed.


Mechanism of energy coupling for transport of deoxycytidine, uridine, uracil, adenine and hypoxanthine in Escherichia coli.

The transport processes for uridine, deoxycytidine, uracil, adenine and hypoxanthine require an energy source and are active under anaerobic or aerobic conditions. Inhibitory effects of cyanide, arsenate, carbonylcyanide m-chlorophenylhydrazone, 2,4-dinitrophenol and N,N'-dicyclohexylcarbodiimide on the transport of uridine and deoxycytidine differ from the corresponding effects on the transport of uracil, adenine and hypoxanthine. The nature of these inhibitory effects supports the conclusion that uridine and deoxycytidine transport is energized either by electron transport or by ATP hydrolysis via (Ca2+ + Mg2+)-ATPase. The transport or uracil, adenine and hypoxanthine is dependent upon ATP or some high energy phosphate derivative of ATP, but is independent of (Ca2+ + Mg+)-ATPase and electron transport. Uptake of the ribose moiety of uridine by a mutant of Escherichia coli B, which lacks the transport system for uracil and intact uridine, is neither stimulated by energy sources nor inhibited by various inhibitors of energy metabolism under either aerobic or anaerobic conditions.


The primary structure of Escherichia coli K12 aspartokinase I-homoserine dehydrogenase I-Isolation and characterisation of the peptides produced by cyanogen bromide.

The aspartokinase I-homoserine dehydrogenase I from Escherichia coli K12, composed of four identical subunits of molecular weight 86,000, was carboxy-methylated, fragmented by cyanogen bromide treatment and citraconylated. Using gel filtration, ion exchange chromatography and preparative paper electrophoresis and chromatography, 15 of 21 cyanogen bromide peptides were isolated in pure form and characterized by their composition, their N-terminal amino acid, and by their content of known cysteinyl or tryptophanyl tryptic peptides.


A selected bibliography of biomedical and environmental applications of stable isotopes. III--15N 1971-1976.

A compilation of selected references of the use of 15N in biochemical, pharmacological, clinical and environmental applications for the period 1971--1976 is presented. Author and subject indices have been compiled to enable the reader to make further use of this information.


A selected bibliography of biomedical and environmental applications of stable isotopes. IV--17O, 18O and 34S 1971--1976.

Selected references to the biochemical, pharmacological, clinical  and environmental applications of the stable oxygen isotopes, 17O and 18O and of 34S have been compiled for the period 1971--1976. Author and subject indices have been prepared for each element.


A profile of health sciences libraries in Southeast Asia.

This paper reports the results of a survey undertaken by the World Health Organization of health sciences libraries in Southeast Asia. It includes information on clientele, budget, personnel, collections, lending policy, dissemination of information, and reference services. The survey indicates that the collections in most of the health sciences libraries in Southeast Asia are deficient and that services provided to readers are inadequate. Recommendations for improvement are outlined.


[Heat induced structural transformations in Escherichia coli membranes in the presence of Ca2+].

Using an uncharged hydrophobic fluorescent probe 4-dimethylaminochalkon (DMC) the thermotropic behaviour of cytoplasmic E. coli membranes in the presence of Ca2+ cations was investigated. DMC appeared to be very sensitive in detection of temperature induced phase transitions in E. coli membrane preparations. It was found unexpectedly that Ca2+ does not increased the phase transition temperature of membrane preparations, compared to the values calculated for the membranes in tris-HC1-buffer. The obtained results are briefly discussed.


Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells.

A 22-yr-old man with acute myelocytic leukemia received a bone marrow transplant from a genotypically HLA-identical female sibling after cyclophosphamide preparation. He remained in complete remission for 18 mo, when he developed a chloroma in the perineum. The chloroma was treated with local radiotherapy. The chloroma recurred 8 mo later and was treated with radiotherapy followed by combination chemotherapy. At 34 mo after transplant, marrow relapse and chloroma were documented. The first chloroma contained host cells by fluorescent Y-chromatin body analyses of interphase nuclei. All metaphase cells and karyotypes from peripheral blood and marrow samples showed no evidence of host cells from 3 wk after transplant through the time of marrow relapse. Data from autosomal and sex chromosome studies indicate that the marrow relapse occurred in cells of donor origin. A new consistent chromosome abnormality [45, X, -X, t(8;21) (q22; q22)] was observed in a majority of donor cells. The patient received a second bone marrow transplant from the same donor after preparation with busulfan and cyclophosphamide and attained a complete remission with full hematologic engraftment.


MEDLINE training within the library school curriculum: quality control and future trends.

In order to assess the current status of MEDLINE training provided by schools of library science, a survey was conducted of those schools having an educational identification code issued by the National Library of Medicine. Information was gathered on such variables as the instructors' background and preparation, the course objectives and content, and the amount of on-line experience provided to students in each of eleven programs. An evaluation of these measures indicates that more opportunities to gain experience in using MEDLINE should be initiated by library schools and that current efforts should be continued and expanded. Specific recommendations for accomplishing these goals are outlined; they are addressed to health sciences librarians, library school educators, the Medical Library Association, and the National Library of Medicine.


A specialized information center. The clinical neurology information center.

The history, philosophy, and methodology of a unique specialized medical information center are reported. The Clinical Neurology Information Center is an educational information service (giving its audience information which can be the basis for formulating their own questions) rather than an instructional information service (giving information in reply to questions). Clinical, as well as basic neuroscience, information is culled by professional neurologists from 855 medical periodicals. The essence of each article is summarized in a single sentence ("terse conclusions") or a bibliographic reference only is given; this material is published every two weeks in the Concise Clinical Neurology Review (CCNR). The format of the CCNR is such that the reader should be able to scan a very large amount of current literature by investing only twenty to thirty minutes every two weeks. The values of this system as well as some of its problems are discussed.


Comparison of American medical dictionaries.

Although American medical dictionaries are a valuable part of any medical library collection, the attributes of each of the four major dictionaries are often unknown and the reference material contained in each unused. The medical librarian should be aware of the differences and values of each dictionary and try to have at least one edition of each available to library users in order to maintain an adequate reference collection.


A gastrocnemius musculocutaneous flap.

The results of injection studies in cadavers and in vivo flap construction suggested that a flap based on the medial or lateral gastrocnemius muscle and the skin of the popliteal fossa draining to the long or short saphenous systems respectively provides a good length to breadth ratio flap without prior delay. Such a flap based on the medial gastrocnemius muscle was used successfully in 1 patient.


Experimental flap delay with formic acid.

Using dorsal, cranially based 10 X 3 cm composite pedicle flaps in rats, the effects of an injection of 2 ml of formic acid in different concentrations was studied. Concentrations of 0.2 per cent gave a very significant increase in flap survival over controls. Preoperative penicillin did not influence the outcome.


Fibrous reactions in the tissues which surround silicone breast prostheses.

Fibrotic reactions in adipose tissue, in the pectoral muscle and in the mammary gland are described. These were provoked by trauma to those tissues during implantation. Such reactions cause thickening of the capsule around the implant, and may be contributory factors in constrictive fibrosis.


Serum calcium and magnesium in schizophrenia: relationship to clinical phenomena and neuroleptic treatment.

Serum calcium and magnesium were studied in drug-free and neuroleptic-treated schizophrenic patients. Calcium and magnesium were not significantly different in 31 unmedicated schizophrenic patients compared with normal controls. Serum calcium was altered, however, in two subgroups: (1) Patients who remitted after neuroleptic withdrawal were significantly lower in calcium than those who did not remit; (2) catatonic schizophrenic patients appeared to have an increased calcium at the onset of catatonic stupor. Patients treated with pimozide were found to have a significant decreased in both calcium and magnesium compared with their drug-free values. These same patients showed a similar decrease in both electrolytes during treatment with fluphenazine, a structurally different neuroleptic drug.


Trials of lithium, chlorpromazine and amitriptyline in schizoaffective patients.

Two drug trials in schizoaffective patients are reported. Nineteen "schizomanic" patients were treated for one month, on a double blind basis, with chlorpromazine or lithium and 41 "schizodepressive" patients with amitriptyline, chlorpromazine or both. In the schizodepressive patients there was a trend to a better response to chlorpromazine, but drug response generally was poor, only 20 per cent of patients recovering within the month. In the schizomanic patients lithium seemed as effective as chlorpromazine, which supports the view that these patients were suffering from a variant of mania.


The neuroleptic hypothesis: study of the covariation of extrapyramidal and therapeutic drug effects.

A therapeutic trial with chlorpromazine was conducted with a homogeneous (for age and sex) group of recently admitted schizophrenic patients. Extrapyramidal effects were measured through quantitative analysis of digital tremor, after four days of fixed-dose treatment. Assessment of treatment efficacy was based on Brief Psychiatric Rating Scale ratings, done at the end of four weeks' treatment. Those patients whose tremor was least affected by drug were most likely to benefit from the treatment. Implications of this negative correlation for our understanding of the neuroleptic hypothesis and the closely associated dopamine hypothesis of schizophrenia are discussed.


A method of grafting hand burns following early excision.

Early excision and delayed primary grafting of burns of the hand is presented as a method of achieving rapid healing, thus allowing early full mobilization. The results of 19 consecutively treated patients are reported.


Influence of bowel preparation and antimicrobials on colonic microflora.

The influence of three types of preoperative mechanical bowel preparation on colonic microflora has been studied in 88 patients undergoing elective bowel resection and compared with 21 controls. Neither conventional bowel preparation (CBP) using oral magnesium sulphate, enemas and rectal washouts nor whole bowel irrigation (WBI) via a nasogastric tube influenced the type or number of organisms in the colon at the time of operation. The administration of an elemental diet (ED) was associated with only a small reduction the numbers of Escherichia coli (P less than 0.02). The addition of oral neomycin and metronidazole for 48 h before operation to all three methods of bowel preparation was associated with a highly significant reduction in the counts per ml of E. coli (P less than 0.001) and Bacteroides fragilis (P less than 0.001) in the colon. There was no correlation between the diameter of the lesion being resected with the numbers of bacteria in the colon even when oral neomycin and metronidazole were added to the bowel preparation.


Primary suture of the perineal wound following rectal excision for inflammatory bowel disease.

Delay in healing of the perineal wound is a major cause of disability in patients after excision of the rectum. The outcome of primary suture in 76 patients treated at St Mark's Hospital between 1967 and 1976 was correlated with a number of factors describing the patients, their preparation for surgery and details of surgical technique and management. The perineal wound healed by first intention in 33 patients. The remaining 43 patients regarded as failures included 7 with delayed breakdown after initial healing. The results showed that women fared better than men. Excision of the rectum following colectomy and ileostomy was associated with failure of the perineal wound to heal in 9 out of 10 patients. Treatments with peroperative ampicillin and topical antibacterial agents were both correlated significantly with success. Preoperative sepsis and operative contamination were followed by perineal sepsis and wound breakdown on 16 out of 21 occasions. Discriminant analysis showed that topical and peroperative antibacterial treatments, sex, preoperative sepsis and finally ACTH were the most important variables in descending order of importance. The prediction of success and failure by this procedure was 72.4 per cent correct.


Autoimmunity in juvenile diabetics and their families.

Pancreatic islet cell, thyroid, and gastric antibodies were studied in 116 young insulin-dependent diabetics and 257 relatives. Seventy-four per cent of the diabetics studied within three months of diagnosis had islet-cell antibodies but only 20% of those studied three years or more after diagnosis. Persistence of these antibodies was associated with a high prevalence of thyrogastric autoimmunity, which suggests that some cases have an aetiology similar to that of "polyendocrine" autoimmune disease. Retinopathy or nephropathy, or both, was present in 10 diabetics, who were all members of "autoimmune" families, in which one or more members had organ-specific antibodies. Nine of the 10 healthy relatives with islet-cell antibodies and all families with more than one diabetic were also in this autoimmune group. These data suggest that an autoimmune factor may contribute to juvenile diabetes and that such autoimmune diabetes has a tendency to run in families and may be more likely to cause complications.


Renal vein renin measurements in children with hypertension.

Renal venous renin activity was measured in 50 children with hypertension. Main renal vein and segmental renal vein sampling was feasible in children as young as 15 months. In all cases in which there was a clear difference in renin secretion between the kidneys--that is, a main vein renin ratio above 1.5--surgery, when undertaken, successfully restored normal blood pressure. Most of the children with main renal vein renin ratios below 1.5 had bilateral disease or apparently normal kidneys. Segmental renal vein sampling contributed useful information additional to that provided by main renal vein measurements and permitted identification of local sources of renin production. In children with renal transplants who developed hypertension renal vein renin measurements helped in determining the cause and facilitating the management of the raised blood pressure.


Prophylactic co-trimoxazole in biliary surgery.

A double-blind study was conducted to test the prophylactic effect of a single dose of co-trimoxazole on the incidence of septic complications after elective cholecystectomy. Forty-eight patients received co-trimoxazole and 47 placebo. Wound sepsis occurred in 10 (21%) of the controls but in only 2 (4%) of the treated group, and the incidences of pulmonary complications were 49% (23 cases) and 19% (9) respectively. These differences were significnat. Wound sepsis after cholecystectomy occurs mostly in patients with infected bile. Co-trimoxazole given by intravenous infusion rapidly achieves a high concentration in the palsma and is effective against most biliary pathogens.


Monitoring aminoglycoside use in patients with severely impaired renal function.

Twenty patients with severely impaired renal function, 17 of wnom had recently transplanted kidneys, were treated with aminoglycosides for severe infections acquired in hospital. Serum aminoglycoside concentrations were closely monitored and dosages adjusted individually to obtain peak and trough concentrations that ensured adequate treatment while avoiding toxicity. Causative organisms were susceptible to treatment in 21 out of 26 episodes of infection (81%), and 12 of the 17 patients (71%) in whom organisms were isolated were cured. Nephrotoxicity attributable to aminoglycosides alone was not observed during the 35 courses of treatment. Ototoxicity occurred in only one patient, who had excessively high serum concentrations of amikacin. Serum aminoglycoside concentrations were directly affected by carbenicillin and flucytosine. The concurrent administration of cephradine and cephalexin with gentamicin may have produced nephrotoxicity. We conclude that aminoglycosides, when carefully monitored, are effective and safe in patients with severely impaired renal function.


Attachment of virulent Treponema pallidum to human mononuclear phagocytes.

The predominant phagocyte in established human syphilitic lesions is the mononuclear phagocyte. As these leucocytes may be important in immunity to Treponema pallidum, the initial interaction between human phagocytes and pathogenic T. pallidum (Nichols strain) was studied in vitro. Motile, virulent T. pallidum attach to the surface membrane of phagocytes but are not ingested by these cells. Heated, non-motile treponemes are not cell-associated but are observed free in the extracellular medium. Attachment is polar, at one or both terminal portions of the treponeme, and is neither serum- nor complement-dependent. Ingestion of virulent treponemes was not observed by phase-contrast or by electron microscopy in the presence of normal human or rabbit serum and complement. Techniques were chosen to preserve both the fragile surface constituents of the treponeme and the phagocytic function of mononuclear cells. Unfixed preparations were observed by phase-contrast microscopical examination during incubation to differentiate motile from non-motile organisms and fixed preparations were used for quantitation of attachment. This model should be useful for studying humoral and cell-mediated immunity in syphilis.


Genital chlamydial infections in patients attending a gynaecological outpatient clinic.

Investigation for genital chlamydial infections was carried out on 160 patients of fertile age attending a gynaecological outpatient clinic. Thirteen (9%) of the 144 patients with valid specimens were found to be Chlamydia-positive. Seven (54%) of them had antichlamydial antibodies by the complement-fixation test, and 11 (85%) antichlamydial antibodies by a single-antigen immunofluorescence test compared with 21 (16%) and 70 (53%), respectively, of the 131 Chlamydia-negative patients. Patients with overt genital chlamydial infection often complained of ocular and urethral symptoms. Usually there was clinical evidence of cervical infection as well as of inflammation on cervicovaginal smears. Colposcopical and histological examinations did not show any specific alterations.


Early malignant syphilis observed during infection and reinfection in the same patient.

Malignant syphilitic infections occurring in the same woman at an interval of 38 months is reported. The first infection was diagnosed as secondary papulopustular and ecthymatous syphilis. The reinfection was more severe, taking the form of secondary ulcerative syphilis with fever, general deterioration, and loss of weight. Numerous Treponema pallidum were present in the serum expressed from the papulopustular lesions during the first infection, but they were absent from the secretion expressed from the margins of the ulcerative symphilides during the reinfection. Many treponemes were present in the plasma cell infiltrates in histopathological sections of the biopsy specimens taken from the margin of the ulcers.


Antibiotic resistance patterns of fecal coliforms isolated from domestic sewage before and after treatment in an aerobic lagoon.

The resistance of 260 strains of fecal coliforms, isolated from raw domestic sewage and aerobic lagoon effluent, to ampicillin, aureomycin, chloromycetin, gentamicin, streptomycin, sulfadiazine, and tetracycline, was determined. Aerobic lagoon treatment produced a 20-fold reduction in the fecal coliform numbers. No statistically significant difference in antibiotic resistance was observed between the fecal coliforms found in raw sewage and in lagoon effluent despite a trend towards the loss of resistance in the latter. Antibiotic resistance, either single or multiple, did not contribute to, or detract from, bacterial survival in the aerobic lagoon. Of the isolates, 15% showed resistance to two or more antiobiotics.


Parathyroid hormone and hyperparathyroidism: current concepts.

Our expanding knowledge of the physiologic and biochemical factors governing calcium homeostasis has improved our capacity to evaluate hypercalcemia, of which an increased incidence is being discovered through the widespread use of multiphasic screening. Consequently, we are diagnosing mild forms of hyperparathryoidism more often than formerly. The enhanced recognition of virtually symptom-free hyperparathyroidism presents a problem in patient management because the natural history of this form of hyperparathyroidism is unknown and the pathologic lesion underlying the condition may be ambiguous, resulting in difficult decisions in surgical management. Further study is required to resolve this issue in order to provide optimal care for the affected individual.


Surgical considerations in hyperparathyroidism: current concepts.

The pathologic and histologic alterations seen in the parathyroid glands removed at operation have changed dramatically in recent years as a result of early diagnosis and treatment, often in asymptomatic patients. This situation has resulted in considerable disagreement over optimal surgical therapy and the number of parathyroid glands the surgeon should remove. These areas of controversy are analysed and current concepts critically reviewed.


Immunologic detection of primary carcinoma of the pancreas.

The prevalence of carcinoma of the pancreas is increasing in North America. Primary prevention of this disorder is not yet possible and secondary prevention is difficult because most investigative procedures are either highly invasive or not universally available. The authors tested the efficacy of a simple immunologic assay, the leukocyte adherence inhibition (LAI) assay, in the detection of carcinoma of the pancreas. They investigated 55 patients who were divided into six groups--normal (control) patients (16) and those with carcinoma of the pancreas (9 patients), pancreatitis (15), other intra-abdominal carcinomas (9), obstructive jaundice (4) and pancreatic pseudocysts (2). The LAI assay proved highly effective in selecting patients who, at surgery, were shown to have carcinoma of the pancreas, but was not as effective in the groups. This assay may therefore prove valuable in the early evaluation of patients with a suspected pancreatic malignant condition.


Diabetic glomerulosclerosis: current status.

Current information on the nature, pathogenesis and treatment of diabetic glomerulosclerosis is reviewed. The fundamental lesion is one of the glomerular basement membrane, a complex layer of collage-like and other peptides; thickening of this membrane, seen microscopically, is due to the presence of an increased amount of membrane material of normal composition. There is little reliable evidence relating the frequency of glomerulosclerosis to the quality of control of the diabetic state, but indirect evidence from patients with secondary diabetes and from a variety of studies in animals indicates strongly that the glomerular lesion is a consequence of the abnormal metabolic state and can be prevented by adequate treatment of the diabetes. A concept of the pathogenesis of the glomerular lesions and renal failure is presented, but there remain large gaps in knowledge of the mechanisms involved. Treatment of chronic renal failure by maintenance renal dialysis and renal transplantation is not as successful in persons with diabetes as in those without this condition; however, the results appear to be improving, and transplantation particularly holds much promise.


Kaposi's sarcoma in renal allograft recipients.

The development of Kaposi's sarcoma in immunosuppressed patients is a rare occurrence, but poses a real threat to the patient due to the rapid progression of the unchecked disease. The suspicion of this disease will prompt early diagnosis by scrutiny of histologic preparations and prompt interruption of antirejection therapy. Four of five patients in whom a diagnosis was made preterminally responded favorably to withdrawal of immunosuppressive agents. In renal allograft recipients with mucocutaneous vascular lesions, Kaposi's sarcoma should be considered as a cause of gastrointestinal bleeding.


Gonadal dysgenesis with adenocarcinoma of the endometrium: an electron microscopic and steroid receptor analyses with a review of the literature.

A patient with gonadal dysgenesis who developed endometrial carcinoma in her 31st year of estrogen therapy is discussed in relation to thirteen previously reported cases of carcinoma of the uterus in patients with Turner's syndrome. The pattern of steroid receptor proteins in the endometrial carcinoma was found to correlate with the degree of differentiation of the tumor as assessed by light and electron microscopy. The findings reflect a potential for continued hormonal responsiveness of the tumor.


Ultrastructural investigation of NI3S2-induced rhabdomyosarcoma in Wistar rat: comparative study with emphasis on myofibrillar differentiation and ciliar formation.

Nickel-sulfid-induced rhabdomyosarcomas were studied by both light and electron microscopy. The successive stages differentiating tumor cells were described, and two differentiation types of rhabdomyoblasts could be observed 1) with the characteristic pattern of fetal differentiation--i.e., myofilament apparation before Z-line formation--and 2) with synthesis of these elements in the reverse order. An organized T-system is not evident. The sarcoplasmic reticulum is irregular and its cisternae often contain a granular substance or microcrystals. The only well-developed element of tumoral myofibrils is the Z-line; the other zones of sarcomeres are seldom clearly defined. Several unusual granular structures were observed. No virus particles were found. The formation of cilia appears only in interphase rhabdomyoblasts and has to be considered as aberrant and temporary formations from centrioles. They generally possess a "9 + 0" microtubular pattern, but often could be observed as rudimentary forms with a "7 + 2" microtubular arrangement. This case is another example demonstrating the relationship of cilia formation with cell division, especially after suppression of mitotic control. The histology and the electron microscopy results are discussed in relation to the differentiation pattern and the ultrastructural features of embryonic, regenerating and pathological muscle differentiating in vitro.


Squamous cell carcinoma in situ of the endometrium and fallopian tube as superficial extension of invasive cervical carcinoma.

Five cases of squamous cell carcinoma of the cervix associated with widespread squamous cell carcinoma in situ of the endometrial surface are reported. In one case, carcinoma in situ was also found in one fallopian tube in continuity with the cervicoendometrial lesion. A survey of the literature reveals only 20 cases with similar surface endometrial involvement by cervical squamous cell carcinoma. Of these, the fallopian tubes were involved by an identical lesion in six cases only. Pyometra and cervical stenosis were reported in about 66% of the cases. This rare form of upward cervical cancer extension was present in five of 680 cases (0.7%) of squamous cell carcinoma of the cervix in the file of the Tumor Registry of Magee-Womens Hospital.


Bilateral primary germ cell testicular tumors: report of four cases and review of the literature.

Bilateral primary germ cell tumors of the testicle are rare. The last comprehensive review of the literature (1955) revealed a 1.6% incidence. However, during the past twenty years, cases have been reported more often, raising the questions of increased frequency due to prolonged survival following surgery and/or roentgen therapy for unilateral tumors. A search of the medical journals during the past two decades fails to show any increased frequency of bilaterality (1.56%). All general combinations of cell types may occur and the tumors may appear simultaneously or sequentially. Successive seminomas are seen more often followed in frequency by concurrent seminomas. Although 50% of the second primaries were diagnosed within five years, 3% of the patients developed the second tumor after 20 years, stressing the need for extended follow-up. Factors affecting the diagnosis, management and prognosis of bilateral testicular tumors are discussed. Four additional cases of bilateral germ cell tumors are described.


Carcinoembryonic antigen levels in advanced gastric carcinoma.

Serial CEA levels were measured in 157 patients with advanced inoperable gastric carcinoma entered in a controlled trial of cytotoxic therapy. In 49 (31%) of cases initial levels were greater than 50 ng/ml. However, serial measurements were only possible in 57 (36%) cases and results were prognostically valuable in only 15 (9.5%) of cases.


Lymphomas of the gastrointestinal tract: a study of 117 cases presenting with gastrointestinal disease.

A study was made of 117 patients who presented with gastrointestinal lymphoma. The occurrence was 48 in the stomach, 37 in the small intestine, 13 in the ileocecal region, two in the appendix and 11 in the large intestine. In six cases, multiple sites in the gastrointestinal tract were involved, but in five cases this appeared to be secondary to massive mesenteric or retroperitoneal lymph node disease. Using Rappaport's classification, diffuse histiocytic lymphoma was the most frequent histologic type and constituted 60% of the cases. Nodular lymphomas comprised 10% of the total, nodular poorly differentiated lymphocytic lymphoma forming the majority of this group. Ten of the lymphomas were undifferentiated, 5 of Burkitt's type and 5 non-Burkitt's type. Five were Mediterranean-type lymphomas associated with plasma cell infiltration of the adjacent mucosa, and only two cases of primary Hodgkin's disease were encountered. Two lymphomas could not be classified. Eight percent of the cases showed plasmacytoid changes and were classified as a distinct subgroup of the parent lymphoma rather than as examples of extramedullary plasmacytoma. Gastrointestinally lymphomas occurred most frequently during the fourth to seventh decades. However, nine lymphomas occurred in children younger than 16 years of age. In comparison to adults, the childhood lymphomas showed a number of notable differences with respect to sex distribution, site of involvement and histologic type. Information concerning the extent of the disease at the time of diagnosis was available in 75 cases. Of these, 49% of the lymphomas were confined to the affected viscus and 33% had associated regional lymph node involvement; the remaining 18% had mode widespread disease. In 44 patients information on the spread of disease was available and in 48% there was extra abdominal spread. Prognosis appeared to correlate best with the stage of the disease rather than the histologic type.


Inverted papilloma of the bladder: a distinct urological lesion.

With the addition of six new cases, 104 cases of inverted papilloma of the bladder are reviewed. Pathological and epidemiological characteristics of this distinct bladder lesion are outlined, comparison with transitional cell papilloma is investigated, and recommended therapy and follow-up are offered.


Paratesticular rhabdomyosarcoma in childhood.

The paratesticular region was the primary site in 20 of 289 children (7%) entered on the Intergroup Rhabdomyosarcoma Study. The 20 patients were 1.7- to 19-years-old at diagnosis. Fifteen underwent retroperitoneal node dissection (12) or biopsy (3), and 6/15 (40%) had nodal involvement by tumor. Nineteen of the 20 patients had no gross local or metastatic disease after surgery. All 20 received chemotherapy, and 13 also received radiotherapy. Treatment was effective: 16 of 18 evaluable patients (89%) were free of disease at a median of 23 months from diagnosis (range, 8-43 months). Since the incidence of tumor-involved retroperitoneal nodes is high, a dissection should be performed. If the nodes are free of tumor, retroperitoneal radiotherapy may not be necessary. Reduction of morbidity in patients with paratesticular rhabdomyosarcoma is desirable, because the disease has a good prognosis.


Multiple fibroxanthosarcoma of bone.

A case of multiple fibroxanthrosarcoma of bone is described. Clinically, the patient presented with multiple osteolytic lesions involving the skull, ribs, vertebral body, pelvic bones and proximal femur simulating multiple myeloma or metastatic carcinoma. The histologic features of the lesion fulfilled the criteria established for the recently delineated fibroxanthosarcoma. Three similar cases reported as multiple diffuse fibrosarcoma of bone are reviewed and the terminology for these lesions discussed.


Tumor heterogeneity and the biology of cancer invasion and metastasis.

The development of a metastasis is dependent on an interplay between host factors and intrinsic characteristics of malignant tumor cells. The process of metastasis is highly selective, and the metastatic lesion represents the end point of many destructive events that only a few cells can survive. Neoplasms, which are predominantly heterogeneous, contain a variety of subpopulations of cells with differing metastatic potential. Furthermore, metastatic cell variants have been shown to preexist in murine neoplasms of old and recent origin. The possible existence of highly metastatic variant cells within a primary tumor suggests that we no longer should consider a neoplasm to be a uniform entity. Efforts to design effective therapeutic agents and procedures against malignant tumors should be directed toward the few but fatal metastatic subpopulations of cells.


Mutagenic and recombinogenic effects of the antitumor antibiotic anthramycin.

Anthramycin, one of the pyrrolo(1,4)benzodiazepine antibiotics with potent antitumor activity, was tested for its effects on a number of genetic parameters. The results show that this antibiotic is nonmutagenic in the Ames strains of Salmonella typhimurium while mutagenic in only one and antimutagenic in the rest of the genes tested in the eukaryotic organism Saccharomyces cerevisiae. The antibiotic is, however, a potent recombinogen inasmuch as it induced mitotic crossing over, mitotic gene conversion, and possibly other chromosomal alterations in a diploid strain of S. cerevisiae. These studies emphasize the need for a battery of test systems including eukaryotic organisms to detect the genetic activity of certain antitumor drugs. The importance of considering data distinguishing between highly mutagenic and poorly mutagenic cancer chemotherapeutic agents is also discussed.


Activation of carcinogens and mutagens by rat colon mucosa.

Colon mucosal cells can catalyze the activation of precarcinogens to mutagenic metabolites without the intermediacy of intestinal bacteria as shown in a mutagenesis assay system composed of Salmonella typhimurium strain TA100 and the 9000 X g supernatant fraction of rat colon mucosal cells. Pretreatment of rats with beta-naphtoflavone increased the activation of 2-aminoanthracene 10- to 20-fold and the activation of benzo(a)pyrene 4-fold. Pretreatment of rats with Aroclor 1254 doubled the activation of 2-aminoanthracene over control but had no effect on the activation of benzo(a)pyrene. The activation of 2-aminoanthracene and benzo(a)pyrene by liver was induced significantly by pretreatment with beta-naphthoflavone and Aroclor 1254. Phenobarbital/hydrocortisone pretreatment did not increase the activation by the colon system of any precarcinogen tested but did increase the activation of 2-aminoanthracene, cyclophosphamide, and isophosphamide by the liver system. The activation of precarcinogens in the bacterial test system is directly correlated with the activities of the pretreated colon and liver preparations toward several drug and polycyclic hydrocarbon substrates assayed in vitro.


An automatic device for freeze-clamping of cardiac tissue within a fraction of the contraction cycle.

An automatic quick-freeze clamping device has been developed. Opposed pneumatic pistons filled with aluminium caps previously cooled in liquid nitrogen are used to compress a portion (100 to 200 mg) of the myocardium to a 0.15 to 0.20 mm thick wafer, colling the tissue from 37 degrees C to -15 degrees C within 10 ms. The clamp is triggered electronically from the R-wave of the ECG. This tissue fixation by freezing within 10 ms is sufficiently rapid to study oscillations of myocardial metabolite levels during the contraction cycle of isolated perfused hearts of small mammals such as the rat and guinea pig whose rate is 4 to 5 beats per second.