A normative approach to the definition of primary health care. Primary care is the subject of many pronouncements and many recommendations for change in the literature on health care organization and delivery. Heretofore, there has been no attempt to assess the degree of agreement on the meaning of the term. This paper reports on a normative process used to construct 92 statements about important elements of primary care, and to rank these statements according to their relative degrees of importance in primary care. Three panels--nationally recognized "experts" on primary care, consumers, and public health nurses and social workers--participated in the development as well as the ranking of the statements. The rankings of the national experts are discussed in detail, and brief comparisons are made with the rankings of the consumer and public health worker panels. Experts gave a high ranking to the statements concerned directly with medical services and their linkages. All gave attention to equality and patient dignity. Consumers stressed the need to improve access to primary care services. Public health workers emphasized improvement in both access and the quality of the relationship between patients and providers. The overall findings suggest that increasing the base of participation in primary care planning may bring greater attention to patient defined needs, and that broadening of medical care objectives from medical care to a more inclusive health care is not imminent.


Societal responsibility for malpractice. The purposes of providing just compensation to victims of medical injury and assuring high quality medical care are not served by the tort system. The tinkering with the tort system following the 1975 malpractice crisis will not ease the constantly increasing cost burden on the health care delivery system. Costs will double every three to four years. The only answer is a social insurance approach. The costs of a compensation system for medical injury regardless of fault could be met by eliminating the friction costs of the tort system, and would be helped by establishing national health insurance. The system could be initiated gradually and would be accompanied by quality assurance measures.


[Our experience with reparative and derivative operations for non-cancerous lesions in the extrahepatic bile ducts]. 17 reparative operations on the bile ducts, 7 of which were immediate (5 for peroperative lesions and 2 for "spontaneous" lesions) and 10 reoperations to deal with sclero-cicatricial lesions, were studied. 7 reconstructive operations (plastic or end-to-end anastomosis) and 10 derivative operations with a preference for hepato- or choledocho-jejunostomy on defunctionalized loop were carried out. The former were reserved for lesions without or with minimum loss of substance, the latter for extensive lesions. Operative mortality is high and higher still in immediate interventions. Long term results were good in all cases but one.


[Case of isolated surgical lesion of the right hepatic duct]. A case of isolated surgical wound of the right hepatic duct is presented. Some considerations regarding all the pathogenetic, diagnostic and therapeutic problems are made. It is felt that, in this instance, surgical management was facilitated by the unusual length of the right hepatic duct, which terminated in the infundibulum of the gall bladder, due to a prior anatomical abnormality.


[Our experience in the surgery of bile ducts]. After a brief review of modern techniques for correct diagnosis and therapy of bile duct pathology, a personal series of 955 operations (between 1-XI-1972 and 30-X-1975) is presented. The need for routine peroperative control of VBP and the usefulness of respecting the papilla where it is anatomo-functionally undamaged are stressed. Personal experience shows that the most rational methodology is after papillotomy the application of a prepapillary Kehr incision through a choledochotomy because this presents fewer complications than the transpapillary Kehr incision in calculosis or stenosis of the VBP where bile duct suture is not advisable. With regard to bilio-digestive anastomosis, indications and limitations are discussed and it is suggested that where the patient's general and local states permit, choledochojejunal anastomosis should permit, choledochojejunal anastomosis should be used, with choledocho-duodenostomy only in special cases. Cholecysto-gastro and cholecystoduodenostomy should be reserved for patients in very serious conditions.


[Leiomyoma of the oesophagus].

[Leiomyoma of the oesophagus]. Successful resection of a leiomyoma of the epicardial segment of the oesophagus in a personal cases is reported.


[Findings on the pathology of mesotheliomas and their morphological diagnosis]. The data arising out of an extensive series of necropsies and operations on cases of mesothelioma observed between 1960 and 1974 in Genoa, a town where the incidence of this type of cancer is high, are reported. Macro- and microscopic and traditional histochemical diagnostic criteria are discussed and judgest to be largely insecure for a diagnosis of mesothelioma. In doubtful cases only the use of the electronic microscope is considered valid for diagnostic purposes. Particular attention is paid to the finding of endocytoplasmatic microfilaments of actomyosin type in mesotheliomatous cells and of microvill on free surfaces and at cell interfaces. For comparative purposes, ultrastructural findings in tumours which often involve pleural metastasis and are able to simulate a mesothelioma, are reported.


[Anatomo-clinical calssification of primary tumors of the pleura and possibility of their surgical treatment]. A distinction is drawn between first category includes peduncolates, giant seslocal and diffuse primary tumours of the pleura on anatomopathological grounds. The first category includes peduncolated, giant sessile, and "deceptive" forms; the latter those in which the lung is surrounded by a "pleural" and "serous" mantle. Treatment is discussed and the soundness of surgical management is stressed.


[Anatomo-pathological diagnosis of pleural mesothelioma]. The problems of the anatomo-pathological diagnosis of pleural mesotheliomas are analysed on the basis of macro- and microscopic findings. It is emphasized that histological diagnosis rests above all on the structural polymorphism of the mesothelioma and presents considerable difficulty. It is considered that systematic examinations with the electroni microscope should pave the way to more accurate diagnoses of this tumour.


[Primary malignant tumors of the pleura. Pleural Mesothelioma (P.M.)]. The clinical overture, symptomatology and morphoradiological picture of a personal series of primary pleural tumours (70 mesothelioma and 1 fibrosarcoma) are described. Conventional and more recent instrumental, cytohistological and bioptic methods of diagnosis are explained, with particular reference to pioneering experience gained with fibropleuroscopy in the Genoa Clinical Department. While dependable diagnosis can now be virtually assured, surgical and pneumological management holds out few prospects of success.


[Our experience in the surgical treatment of pleural mesothelioma]. Surgery is of decisive importance in two situations: diagnosis insofar as thoracotomy offers, with very little risk, the opportunity to perform sufficiently ample biopsy; therapeutic because, lacking any other indicated approach, palliative intervention is recommended to stop effusion. 18 decortications (i.e. 40%) and 2 pleuropneumonectomies are reported. Results were good.


[Clinical contribution to the study of congenital pulmonary arteriovenous fistulas]. Three cases of congenital a-v fistulas of the lung encountered in some 10,000 patients examined are reported. Emphasis is laid on the possibility that the disease may be misinterpreted for a long time and treated wrongly. It is considered that the most significant examination for diagnostic purposes is angiocardiopneumography because even in the rare cases in which it does not reveal the fistula, it shows up its existence by the early visualization of the left heart.


[A case of severe obesity treated jejunoileal bypass. 1-year clinical course]. A 40 + 5 cm jejunoileal bypass was created as a means of treating a case of morbid obesity. Clinical, functional and morphological examinations were carried out prior to surgery and at various times for the following year. An initially rapid loss of weight was followed by an early halt around the 7th month and a subsequently steady state. While metabolic and cardiorespiratory benefits were obtained, considerable and progressive hyperchlorhydria and lithiasic cholecystitis were noted, along with minor, reversible complications.


[Case of neurinoma of the cervical vagus nerve in the intertracheoesophageal region]. A case of neurinoma of the vagus nerve localized in the cervical, intertracheo-oesophageal region is described. After a survey of the literature on the subject, the differential diagnosis and operative technique are discussed.


[Mesenteric cysts. Clinical case].

[Mesenteric cysts. Clinical case]. A case of multiple mesentery cysts is presented and the etiopathogenesis, anatomopathology, symptomatology and therapy of this disease discussed.


[Rehabilitation of patients with colostomy]. The psychological and physical problems associated with colostomy are discussed. Techniques with colostomy are discussed. Techniques designed to prevent faecal incontinence and permit intestinal performance in accordance with desired rhythms are indicated. Application of such methods at the Colostomy Rehabilitation Centre, Milan Tumour Institute, has been attended by success on both the physical and the social plance. The importance of forming trained staffs and patient associations for the exchange of experience and assistance in an extra-hospital milieu is stressed.


[Acupuncture analgesia in experimental animals]. Main experimental works on acupuncture analgesia (A.A.) have been examinated and a technique to perform A.A. in rabbits has been described. Furthermore an anatomic study of acupuncture loci used has been given. It is suggested that several mechanisms are involved in A.A., not only limited to stimuli on the posterior horns, but extending to higher levels.


[Acupuncture in daily practice. Headache]. The aetiopathogenesis of headache is explained in a general review of this subject. Attention is directed the various forms of reflexotherapy that can be cmployed in its treatment. Acupuncture is examined in some detail, from both the general and the symptomatic standpoint. Stress is laid on the different picture presented by headache in different patients.


[Traditional acupuncture. Meridians. Circulation of energy. Chinese points. Comments]. A survey of the traditional Chinese terminology for acupuncture lats stress on the fact that, in the light of recent neurophysiological and anatomic studies, certain terms and various interpretations of the acupuncture routes must be rectified to enxure fuller understanding on the part of Western physicians.


[Long-term critical evaluation of hypothyroidism after subtotal thyroidectomy for thyrotoxicosis]. A retrospective study was made of 66 cases in which subtotal thyroidectomy had been carried for hyperthyroid syndromes, mainly of Basedow type, with a view to establishing a more careful selection of thyrotoxicosis candidates for surgery or other management. The reasons for the different findings and post-operation evaluation of performance are analysed in the light of the time of follow-up, mostly within 5 to 15 yr of surgery. Clinical examination in the light of statistical diagnostic indices was supplemented by evaluation of RIA-T3, TSH and T4, and anti-thyroglobulin antibodies. Four different metabolic states were identified: 1) clinical euthyroidism with normal hormone profile (56.1%); 2) latent hypothyroidism, as shown by high TSH, low T4 and normal RIA-T3 (12.1%); 3) frank hypothyroidism, seen in one case only; 4) high TSH, observed as an isolated finding (30.3%). This last group is fully discussed from the prognostic standpoint. It is not considered as an expression of initial hypothyroidism within  the present series and its follow-up range, but as indicative of hypersecretion of an abnormal TSH, or as evidence of an increased hypothalamus-hypophysis axis threshold for the retroactive action of circulating T4 and T3. Attention is drawn to differences between surgical and radio-iodiotherapeutic hypothyroidism. The former, in particular, is less frequent, earlier to appear, and less predictable, whereas the latter displays a gradually increasing pattern.


[Serum gastrin in various diseases of the digestive system. Clinical experience]. Fasting and after meals serum gastrin levels were determined in healthy subjects and patients with different gastroenterological diseases (duodenal and gastric ulcer, hiatal hernia with gastroesophageal reflux, Billroth II gastric resection, atrophic gastritis, Zollinger-Ellison, Ménétrier, chronic calcifying pancreatitis, gastric carcinoma and lymphoma). The results pointed to the usefulness of evaluating both fasting levels and "gastrin curve" after meals as an expression of the rapidity of response of hormone-secreting gastric cells. Calculation of the I.G.O. (Integrated Gastrin Output) must also be carried out to provide a parameter from which the overall ability of G cells to secrete in response to feeding can be assessed.


[Cushing's ulcer. Various physiopathological studies and considerations]. 28 cases of acute Cushing's ulcer observed out of 2670 necropsies at the S. Spirito Hospital of Rome are reported. Special attention is paid to the most recent physiopathological aspects of the condition.


[New apparatus for the treatment and reinfusion of ascitic fluid]. A new apparatus for the reinfusion of ascitic fluid, offering effective clarifying action as well as the typical concentration of this therapeutic technique is presented.


[Studies on the risk factors of arteriosclerosis in a health district region of Lombardy]. Atherosclerosis risk factor, 8,5% two, 2,7% three and 0,6% four.rs have been investigated in 194 males and 135 female, 25 years old. Elevated lipids were found in 7,3% of the sample; "labile" and stable hypertension in 2,7%; diabetes mellitus in 2,7% and overweight in 19%. 19% of the subjects smoked more than 20 cigarettes daily. Prevalence of hyperlipemia and electrocardiographic changes was higher among people in the lower socioeconomic classes. Taking into consideration hyperlipidemia, hypertension, cigarette smoking, overweight and diabetes mellitus as risk factors, 25% exhibited one risk factor, 8.5% two, 2.7% three and 0.6% four.


[Problems in the use of antibiotics and chemotherapeutics]. Antibiotics are of the greatest utility for the patient, but are sometimes troubling for the physician. The Author, from a standpoint different from that of the pharmacologist, speak about the many things that should be kept in mind whenever a treatment with such drugs must to be performed. Only so a therapy can be safe and effective.. The Author suggest a syndromic approach to recognize which is the causative agent of the current disease, and of consequence, which is the drug of choice. Antibiotics and chemiotherapeutic agents are briefly examined in their usefulness, limitations and side-effect. The new drugs, not yet available in Italy, are cited.


[Results of surgery for mitral valve stenosis]. Long-term follow-up of 1806 patients si subjected to mitral commisurotomy and 122 fitted with a prosthesis for stenosis is described. Of those operated by means of the closed technique, 70% were in functional stage I or II after 10 yr (55% after 15 yr). It would seem from these results that surgery has an important effect on the natural history of mitral stenosis when treated solely medically.


Basal cell carcinoma of the eyelids: a review of patients treated by surgical excision. A study of 107 cases of basal cell carcinoma involving the eyelids in 106 patients all treated by surgical excision was undertaken. The lesions were found predominantly in Caucasians, showed no sex predilection (except for the fact that all five cases under age 40 occurred in females), and were most prevalent in the 7th decade of life. The most common presenting symptom was a mass or growth, while the duration of symptoms of any kind referable to the tumor was 20 months. The lower lid was the most common site of involvement, followed in order of frequency by the upper lid, medial canthus, and lateral canthus. Excised lesions that show marginal involvement histopathologically will not necessarily clinically recur, although this study did show that incomplete excision will more likely show a clinical recurrence in previously treated rather than primary lesions. If basal cell carcinomas of the eyelid are fully surgically excised as a first procedure, the patient will have about a 99% cure rate. Lesions requiring orbital exenteration are rare.


Self-curing methyl methacrylate: Is it safe? Self-curing methyl methacrylate has been recently abandoned by some ophthalmic surgeons because of more than 20 deaths associated with its use in orthopedic surgery. The mechanism of cardiovascular collapse noted in orthopedic cases appears to relate to the surgical procedure as well as a direct vasodilation caused by free monomer. There are no reported cardiovascular complications with the facial uses of self-curing methyl methacrylate. Toxicities to this substance are noted. Ophthalmologists should be aware of these problems and their management. Careful preoperative cardiovascular evaluation, intraoperative patient monitoring, and a well-ventilated operating room are recommended with its use. The review finds no evidence to condemn the ophthalmic uses of self-curing methyl methacrylate because of cardiovascular complications. The search for more inert synthetic compounds should continue.


The racquet conjunctival flap.

The racquet conjunctival flap. In situations requiring a conjunctival flap to cover a corneal defect, the racquet flap technique is a simple relatively noninvasive method. Less conjunctiva is sacrificed and yet the flap is fully maintained by the one pedicle. The bulbar conjunctiva is maintained in an essentially normal state.


Pathophysiology and treatment of corneal hydrops. The new application of thermokeratoplasty as a treatment of both acute and chronic hydrops is presented as a possible alternative to present treatment regimens. The histopathology of keratoconus and hydrops is reviewed relating to thermokeratoplasty effect. Clinical success was achieved in the elimination of pain from advanced chronic hydrops. With the closure of the breaks in Descement's membrane central corneal clearing occurred. In cases of total hydrops although complete resolution of the edema was not always found sufficient, clearing of the corneal periphery allowed for successful penetrating keratoplasty.


Rotoextractor evacuation of total hyphema. Hyphema was created in ten albino rabbits and removed within an hour by the Douvas Rotoextractor. All the blood was gone from each eye within 48 hours and there was no evidence of damage to iris, cornea or lens after six weeks. One patient underwent Douvas Rotoextractor removal of a hyphema that was causing increased intraocular pressure and corneal staining. Three months postoperatively, vision was 6/7.5 and intraocular pressure was controlled.


Glaucoma surgery in Nigerian eyes: a five-year study. A five-year study of 419 sclerectomies and 612 trabeculectomies has been reported. Early and late postoperative complications have been discussed and the relative effectiveness of the operations in controlling intraocular pressure in chronic simple and chronic angle closure glaucoma compared.


Subconjunctival gentamicin prophylaxis against postoperative endophthalmitis in the rabbit. An experimental aphakic rabbit model was employed in order to evaluate the correlation of the clinical course of postoperative endophthalmitis and the ability to recover microorganisms in the postoperative time period, the ocular antibiotic penetration of gentamicin, and the value of antibiotic prophylaxis. 2. Staphylococcus aureus is far more pathogenic organism than Staphylococcus epidermidis. A concentration of 5,000 organisms resulted in an 88% infection rate whereas 50,000 organisms and greater resulted in 100% infection rate after extracapsular cataract extraction. 3. Staphylococcus aureus could be isolated from the eyes demonstrating infection following cataract extraction for 2 days (3 days in one case) and then could no longer be recovered despite the persistance of intraocular inflammation. 4. The infection which appeared in animals receiving 5,000 organisms of Staphylococcus aureus after peripheral iridectomy was significantly milder than that which occurred following cataract extraction. In addition, the microorganisms could only be isolated on the first postoperative day. 5. When 20 mg of gentamicin sulfate was administered subconjunctivally following the post-cataract extraction or post-iridectomy administration of the 5,000 organisms of Staphylococcus aureus, none of the eyes developed clinical signs of endophthalmitis nor could bacteria be recovered. 6. Subconjunctivally administered gentamicin sulfate rapidly penetrated into the aphakic rabbit eye; 75-100 mug/ml appears in the aqueous humor at 1 hour and persists in bactericidal concentrations for at least 4 hours in both the treated and contralateral eyes. 7. Antimicrobial (subconjlnctival gentamicin sulfate 20 mg/prophylaxis at the time of surgery in the experimental animal significantly reduced the incidence of experimental postoperative bacterial endophthalmitis.


Intraocular lenses: visual results and complications. A comparative study. The visual results, and the complications, in 100 consecutive Copeland lens implantations combined with intracapsular cataract extraction, are compared with 100 age matched intracapsular cataract extractions without intraocular lens implantations. The visual results are not significantly different (Tables I and II). Patient satisfaction was excellent. The complications, likewise, are not significantly different (Tables III and IV). There were only two dislocations and one implant corneal touch that can definitely be attributed to the presence of an intraocular lens. The dislocations, although a nuisance, left no residual damage. Cystoid macular edema was no more frequent than without implantation. There were no retrolental membranes causing impairment of vision, no late anterior chamber hemorrhages from lens iris chafing or pressure and no lens related glaucoma. Iritis was insignificant and easily controlled with steroids in the few cases observed.


The circular loop intraocular lens.

The circular loop intraocular lens. A large series of cases of intracapsular cataract extractions with implantation of the recently introduced Medallion circular loop lens is reviewed. Case selection surgical technique, postoperative management, complications and results are presented in detail. Surgical and visual results have been excellent ahd compare favorably with intracapsular cataract surgery performed without artificial lens implantation. The transiridectomy clip of the posterior supporting circular loop provides an excellent system of lens fixation and eliminates the need for an iris suture with the potential long-term complications of possible iris suture absorption. The lens is essentially unluxatable. A particularly low incidence of cystoid macular edema, as well as other long-term postoperative complications, has been encouraging. The surgical technical requirements for implantation of this particular implant are very exacting. Further refinements in design and construction of this artificial lens based on the experiences developed in this series of cases are proposed.


Vitrectomy in sickling retinopathy: report of five cases. The unique problems encountered in sickle patients include the need to remove peripheral vitreous if perfusing sea fans-which can bleed after vitrectomy-are present at the time of surgery. However, peripheral vitrectomy is riskier than central vitrectomy alone. If visualization of the sea fans is sufficient, it is safer to close the sea fans prior to vitrectomy in order to obviate the need for peripheral vitrectomy; then, only central vitrectomy is performed. When sea fans cannot be closed prior to vitrectomy, peripheral vitreous is removed to allow early photocoagulation of the sea fans before they bleed again. Four case presentations illustrate these principles. Vitrectomy relieved severe vitreous traction that complicated retinal detachment in the fifth patient, thereby eliminating the need for a tight encircling structure, which can be poorly tolerated in patients with SC hemoglobin.


Survival rate of patients with choroidal melanoma. A follow-up examination of 214 patients suffering from choroidal melanoma is reported. The frequency of this tumor turns out to be higher in males than in females. There is an increase of relative frequency with age in both female and male patients. The death rate from proven metastases was 34.2% within 5 years. Spindle cell melanomas yield an 85% chance of 5-year survival. Only about 53% of all patients with epithelioid cell melanoma will survive for 5 years. 71% of all patients who died had metastic tumors mainly in liver, bones, and lungs. Most of them had had an epithelioid cell melanoma.


[Classification of retrocorneal membranes]. Retrocorneal membranes can be composed from one layer only -- endothelium, or two layers: endothelium and Descemet, or three layers: endothelium, Descemet membrane and corneal stroma. Besides those corneal membranes which may occur after keratoplasty there are also other forms of inflammatory, degenerative, traumatic or genetic origin. Because diminished corneal transparency often occurs in those cases the precise diagnosis may be difficult on clinical investigation, often only after histological examination the membrane structure may be established.


Free amino acids in the normal and cataractous bovine and human lens capsule and lens. With circular chromatography on paper, we have tested the content of the free amino acids in the normal and cataractous bovine and human lens capsule and lens. The interpretation of the data shows that the normal bovine lens without capsule presents a greater quantity of free amino acids in relation to the bovine cataractous lens without capsule; the lens capsule of normal bovine lens presents a lesser quantity of free amino acids in relation to the lens capsule of the bovine cataractous lens; the normal human lens without capsule presents a relative increase in quantity of free amino acids in relation to the cataractous human lens without capsule (cortical and nuclear cataract); the lens capsule of the normal human lens presents a decrease in the quantity of free amino acids in relation to the lens capsule of the cataractous human lens (cortical and nuclear cataract); the human cataractous lens in "cataracta nigra" presents a marked decrease in quantity of free amino acids in relation to cataractous human lens without capsule (nuclear and cortical cataract), while the lens capsule of "cataracta nigra", presents a marked increase in quantity of free amino acids in relation to the normal human lens capsule, and decrease in relation to the lens capsule of the cataractous human lens (cortical and nuclear cataract).


Hydrodynamic events in the vitreous space accompanying eye movements. Significance for the pathogenesis of retinal detachment. The powers elicited in the vitreous body by eye movements have hardly been subjected to examinations, and the same goes for currents in the vitreous. Model experiments have demonstrated that intra-ocular currents are not elicited by translatory, but so much more by rotatory movements. Furthermore, it is demonstrated that a thin perforated membrane fitted on the inside of the wall of a glass cylinder filled with water, will detach, with rotatory movements. Even minimal rotational movements cause a flow through the hole. It is discussed whether these findings apply to the eye in vivo.


Chemical evolution of photosynthesis.

Chemical evolution of photosynthesis. The principles of biological evolution of photosynthesis are established, but the ways of chemical evolution are unclear yet. The model systems will help to elucidate the problem. Every type of photosynthesis requires photoreceptor absorbing solar radiation. We studied as photoreceptors inorganic components of Earth crust, some coenzymes and porphyrins of abiogenic and biogenic origin. By the aid of inorganic photosensitizers (TiO2, ZnO) the models of photosystems I and II were constructed. Photochemical activation of some coenzymes may serve as an intermediate step from heterotrophic 'dark' to 'light' metabolism. The further evolution led to the separation of catalytic and photosensitizing functions. Porphin, chlorin and bacteriochlorin were formed by abiogenic synthesis. Magnesium complexes of porphyrins are active being excited by light. They are capable to reversible acceptance or donation of an electron to partner molecule. Excited Mg-complexes of porphyrins (P) are capable to transfer an electron from electron-donor (D) to electron-acceptor (A) accompanied by conversion of light quanta energy into potential chemical energy. The primary electron transfer unit (D-P-A) was incorporated into primary membrane. The transition from random to anisotropic arrangement of (D-P-A) in the membrane was plausable as a step of evolution; charge translocation appeared. (D-P-A) units created in the period of chemical evolution were probably used in the course of biological evolution. The (D-P-A) units were coupled with noncyclic and cyclic electron transfer resulting in ATP formation; coupling of two (D-P-A) units led to H2O oxidation and NADP reduction in photosynthetic organisms. The improvement of pigments biosynthesis created the phenomenon of excitation energy migration from the bulk of the pigment to (D-P-A) unit, being reactive center. The models described points the plausible steps of chemical evolution; the real sequence of events will be probably disclosed in the studies of precambrian rocks and space exploration.


The status of tuberculin skin testing at the Pahlavi University Medical Centre. Thirty-four patients with tuberculosis were skin tested with 5 tuberculin units (TU) of purified protein derivative of Mycobacterium tuberculosis (PPD). PPD supplied by Park Davis and Co., Detroit, Michigan, U.S.A. (PPD-PD) as well as PPD obtained from The Razi Institute, Hessarak, Teheran (PPD-RI) were both used for skin testing in each patient. The results indicate that 74-79% of patients with active tuberculosis have positive tuberculin reactions, that PPD-RI is a potent source of tuberculin for skin testing and that a substantial proportion of our tuberculous patients (21-26%) have negative tuberculin skin reactions.


Normal conversion of thyroxine to triiodothyronine in a subject with iodotyrosine-dehalogenase deficiency. BMR, t1/2 of serum T4, and the conversion of T4 to T3 were normal in a patient with iodotyrosine-dehalogenase deficiency who had undergone total surgical thyroidectomy and had been maintained on 200 mug of oral T4 daily. It is concluded that the enzyme system for monodeiodination and conversion of T4 to T3 is different than iodotyrosine-dehalogenase.


An epidemiological approach to the study of Echinococcosis in North-East region of Iran (Khorassan). We have collected all the reported cases of Echinococcus cysts recovered in every surgical ward in Mashhad since their establishment. At the same time we searched corpses of livestock which had been slaughtered in Khorassan's slaughter houses in different days since 1969 for evidence of cysts, and also dogs, 2 wolves, 4 jackals and 11 foxes which had been killed with strychnine, for adult worms. Occurrence of hydatid cyst infestation was found in 478 reports of surgical operations amongst 43,196 cases operated for various diagnosis including hydatidosis. The number of hydatid cyst infestation amongst 15,691 corpses is as follows: 881 out of 12,311 sheep and goats, 378 out of 3380 cattle and camels. The dogs' infestation was rather high as we found adult Echinococcus worms in 50 out of the examined 266, which gives a percentage of 18.79. But no worms could be found in the 2 wolves, 4 jackals and 11 foxes which were examined. All the adult worms examined were Echinococcus granulosus.


Factors related to drug abuse among Iranian university students. Questions related to the use of narcotics were administered to 607 students attending four Iranian universities: Pahlavi University, the University of Tehran, Isfahan University, and Aryamehr University. Twenty-four percent of the students reported that they have used drugs at some time, although only 11% of the students have used drugs more than three times in their lives. Hashish was the most frequently used drug, having been used by 54% of the students who have used narcotics. Ninty percent of the students prefer to ingest the drugs by smoking them. A majority of the students (59%) said that they use drugs for pleasure or to increase sociability. Use of drugs was found to be significantly related to sex, age, number of years of university attended, and father's education. Although proportionately more males than females use drugs, they do not appear to differ significantly from the females in the type of drugs used or the frequency of use. Drug use was not significantly related to the parents' socio-economic status or parents' use of drugs. Exposure to drug use in the university seems to be more closely related to drug use than does parental influence.


Curriculum for the new college of health sciences:  A departure from the traditional medical education. As an outgrowth of the Report of the Imperial Commission on the Study of Health and Medical Problems, The College of Health Sciences was established as the basic educational unit to provide comprehensive health care education within the framework of a team approach to Iranian national health care. The programs are to nonrestrictive, thereby demonstrating the principles of the concept and practice. Because of this, the College is a multidiscipline institution, and will expand to include programs of study in all health care specialties. The program of study for the equivalent of the baccalaureate degree in the College is based on functional analysis of the tasks to be performed by the primary care workers called behdars. The curriculum is task oriented and is made up to two sections, each of 33 months instruction. The first year concentrates on basic functional science and medicine in an academic setting, and the following two years are spent in clinical training in geographically diverse dispensaries and health care facilities. The second stage of the academic program will be available to graduate behdars who have successfully completed two or more years of work in the health care network and who display academic and professional excellence. Through a unit system approach these candidates for doctor of medicine will complete eleven months or more of comprehensive instruction in functional basic sciences, and this will be followed by two years in comprehensive hospital internship.


An experiment in integrated teaching of anatomical sciences. With the phenomenal expansion of knowledge in both basic and clinical sciences, it is absolutely essential to provide a sound foundation of anatomical sciences for the clinical teaching within the limited time available. Problems like shortage of qualified teachers in anatomy, isolation of anatomical sciences from the rest of the basic and clinical departments and multicentricity of sections of anatomical sciences urged us to apply an integrated system as tailored to our needs and limitations. By interdepartmental integration of gross anatomy, histology and embryology a more coordinated teaching has been achieved. Joint clinicoanatomical presentations by participation of anatomists in clinical teaching and clinicians in teaching of anatomy have not only upgraded the teaching but have also significantly reduced the problem of teachers shortage. These presentations are essentially directed towards illustrating the living anatomy, diagnostic anatomy, operative anatomy, applied embryology and microanatomy or the selected regions, with bearings on physical examination, pattern of the diseases, diagnostic and surgical procedures, genesis and treatment of congenital defects and neuroanatomical localisation of lesions. Fundamental basis of developmental and genetic defects are dealt with by a team of pediatrician, pediatric surgeon and the anatomists, with additional emphasis in the genesis of these defects and resultant disorders of function.


Malignant struma ovarii.

Malignant struma ovarii. A rare case of malignant struma ovarii is presented. The tumor was excised together with the ovary and interpreted as a papillary strumal adenocarcinoma arising in a cystic teratoma with predominant thyroid elements. Prior to surgery the patient did not show any symptoms of thyroid hyperfunction. The thyroid function tests performed subsequent to surgery were within normal limits. Periodic examinations of the patient over a period of three years did not reveal any abnormalities. Statistically, this type of malignancy carries a good prognosis with a high "cure" rate.


Studies on the modification of renal lesions due to aspirin and oxyphenbutazone in the rat and the effects on the kidney of 2:4 dinitrophenol. Cortical tubular necrosis induced by either aspirin (300 mg/kg) or oxyphenbutazone (444 mg/kg) was reduced if probenecid (300 mg/kg) was administered at the same time. The prior administration of aspirin (600 mg/kg) reduced the tubular necrosis that follows administration of oxyphenbutazone (444 mg/kg) alone, thus demonstrating that some degree of cross-tolerance between the two drugs occurs. Phenacetin pretreatment (597 mg/kg) was less effective, while paracetamol (503 mg/kg) was without effect in this regard. Those substances that reduced the oxyphenbutazone-induced cortical lesion also ameliorated the focal degenerative change in the lower nephron attributed to this drug. Oral administration of 2:4 dinitrophenol (20 mg/kg) led to only minor cortical tubular necrosis in a few animals.


Pulmonary skin embolism: a case report.

Pulmonary skin embolism: a case report. The incidental autopsy finding of an embolic fragment of skin partially occluding a pulmonary artery is described. It is suggested that the "graft" resulted from one of many needle punctures.


Terminal ileitis, mesenteric lymphadenitis and appendicitis due to Yersinia pseudotuberculosis type VA: case report. A case of terminal ileitis, mesenteric lymphadenitis and appendicitis is reported. Serological studies indicated infection with Yersinia pseudotuberculosis type VA. The patient's illness ran a chronic course necessitating resection of the terminal ileum. Histological examination of the appendix and a mesenteric lymph node in the acute stage revealed granulomas with central necrosis. This is the first human case in which the subtype VA has been identified.


Changing clinical, morphological and immunological patterns in chronic lymphocytic leukaemia. Two cases of chronic lymphocytic leukaemia are presented in which, in the terminal phase of the disease, a population of abnormal lymphocytes similar to those seen in lymphosarcoma cell leukaemia replaced the morphologically normal small lymphocytes observed previously. Immunologically, this change coincided with a striking alteration in the pattern of surface immunoglobulin markers. In both cases, most cells initially carried IgM and in both cases these were replaced by cells carrying IgG as the number of abnormal lymphocytes increased. In addition, the use of anti-delta antiserum in the second case revealed the coexistence of large numbers of IgD-bearing lymphocytes as well. Calculations showed that more than half the cells present at that time must have been carrying both IgD and IgG surface markers.


Catecholamine, indolealkylamine and calcium levels of human pineal glands in various clinical conditions. One hundred and forty-four human pineal glands obtained at necropsy were analysed for their content of catecholamines, indolealkylamines and calcium and the findings related to sex, age, terminal illness and medication. A preliminary study of 45 pineal organs revealed no significant differences in amine pattern in glands removed 6-48 hours post mortem. A statistically significant difference of pineal weight, calcium and amine content could not be detected in glands of age-matched groups of male and female patients who died suddenly without apparent clinical illness. A highly significant correlation between pineal weight and calcium content was established in patients older than 60 years. Considerable variability of amine levels existed in all groups of patients. Adrenaline as well as noradrenaline were detected in most glands. This finding was corroborated by the formation of radioactively labelled adrenaline from noradrenaline and 14C-S-adenosylmethionine by extracts from human pineals. Dopamine was most abundant in glands from patients dying of malignant tumours. The content of the indolealkylamines (5-hydroxytryptamine and melatonine) varied between a few nanograms to 21 mug/g tissue. The highest mean calcium content was detected in glands of patients who died of renal disease associated with hypertension.


The effects and morphology of atheroembolism in limb arteries: an experimental study. Eroded atheromatous plaques which have released atheromatous material into the circulation are commonly found at autopsy in the abdominal aorta and common iliac arteries in man. In an attempt to study this phenomenon quantitatively, human atheromatous material in suspension was injected intothe femoral and common iliac arteries in rabbits. The weight of atheromatous material injected was varied. There was a critical load for the common iliac artery beyond which there was progressive ascending thrombosis and death of the animal. In rabbits weighing 3 to 5 kg, up to 0.2 g of atheromatous material could be injected intra-arterially with survival of the animal and without producing observable effects. As the amount was increased there was a narrow zone in which survival of the animal with a limp occurred. Beyond 0.2 g, death resulted from ascending thrombosis of the peripheral limb arteries. This eventually reached the bifurcation of the oarta and obstructed the opposite common iliac artery. A thrombus rapidly formed around the atheromatous material. Examination of the atherothrombus by light, transmission electron and scanning electron microscopy showed that it contained cholesterol crystals, lipid material, many platelets, leucocytes and red cells bound together within a fibrin net. The atheromatous material was for the most part in the core of the thrombus.


Necropsy findings in childhood leukaemia, emphasizing neutropenic enterocolitis and cerebral calcification. In 50 necropsies on leukaemic children, the major cause of death was infection. In patients dying during therapy for induction or reinduction of remission, the most frequent infection was a distinctive neutropenic enterocolitis or typhlitis. This was seen in 46% of the whole series and was a major factor in the death in 38%. Other infections were predominantly bacterial pneumonia in patients in relapse, and viral disease, e.g. measles pneumonia, in those in remission. One patient treated for meningeal leukaemia showed an unusual linear calcification of the cortical grey matter.


Necrotizing and giant cell granulomatous phlebitis of caecum and ascending colon. A distinctive form of necrotizing and granulomatous phlebitis of a segment of large intestine is described in a previously healthy 36-year-old woman who presented with sudden severe abdominal pain and diarrhoea. At operation the caecum and ascending colon were oedematous and inflamed and right hemicolectomy was performed. Microscopically there was striking involvement of veins in all coats of the bowel ranging from recent fibrinoid necrosis of the whole vessel wall in the case of the caecum, to more chronic giant cell granulomas in parts of the vessel wall with partial or complete occlusion of the lumen in ascending colon. Arteries and lymphatics were entirely spared of these changes. The aitiology of this condition has not been elucidated but the histological appearances and site of involvement suggest an immunological reaction to material absorbed from the bowel. No evidence of food or other allergies or of infection has been obtained. The patient remains symptom free after 18 months. This form of phlebitis does not appear to have been previously described.


A figure-density hypothesis and illusory contour brightness. Perceived figures tend to have surface colour and to be comparatively dense in texture and saturated. These figure characteristics are found in many of the illusory contour figures examined heretofore but new figures presented here do not conform to these characteristics. Consequently, rather than explain subjective brightness effects as offshoots of figural processes, it may be better to begin with concepts of local brightness effects induced by the display, which are made perceptually effective when grouped by the eye.


How good a bet is good form?

How good a bet is good form? 'Good form' theories of perception leave some latitude concerning how casually or cautiously order is imposed on the stimulus. Exploring this issue, the present experiment introduced a series of figures admitting up to three alternative 'good' readings. Eight college students estimated two angles in each of fifty-six pictured spatial forms. Theory predicted that geometrical regularities of rectangularity and symmetry would dominate their estimates. But a regularity would rarely appear when inconsistent with projective geometry and the given figure. The accuracy of subjects' estimates was also assessed. The results confirmed the hypotheses at high significance levels, arguing that such figures are interpreted through an order-imposing process restrained by projective geometry, and that subjects could make roughly accurate estimates based on the imposed order. Parallels with computer scene analysis are discussed. It is concluded that perceptual presumption of certain 'good forms' runs little risk of misinterpreting the stimulus.


Levels of feature analysis in processing visual patterns. In this paper, a revised Pandemonium-like model of visual-feature processing is formulated and a preliminary test of its feasibility is reported. The model differentiates visual-feature processing into a series of hierarchical stages organized by increasing complexity, with the output of each stage going both to the next higher stage, and directly to a more central processor. In the experiment, subjects sorted decks of cards into piles according to the presence or absence of a target stimulus which differed from nontargets in a variety of different features; detection of a feature was sufficient for detection of a target. The data generally supported the revised Pandemonium model, in that targets which differed from nontargets in features thought to be low in the hierarchy were processed faster than targets whose difference was in a high level feature. An extension of the revised model did somewhat less well in predicting the results of sorting for targets in which detection of any one of several features was sufficient for target detection.


On the structure of texture.

On the structure of texture. This paper examines the structure underlying textural patterns. To this end, aspects of a model for texture are developed on the basis of both perceptual processes of the observer and structural properteries of the patterns. Local constructs called primitives serve as generators for globally perfect, but unobservable, ideal textures. Study of the graph representation of these ideal textures reveals the basic regularity underlying visual textures. These perfect patterns are then transformed into observable textures by transformations which must not violate psychophysically based restrictions. Interpretively ambiguous textural patterns are used to demonstrate the influence that local primitives have on the formation of global pattern organizations.


A theory of visual control of braking based on information about time-to-collision. A theory is presented of how a driver might visually control his braking. A mathematical analysis of the changing optic array at the driver's eye indicates that the simplest type of visual information, which would be sufficient for controlling braking and would also be likely to be easily picked up by the driver, is information about time-to-collision, rather than information about distance, speed, or acceleration/deceleration. It is shown how the driver could, in principle, use visual information about time-to-collision in registering when he is on a collision course, in judging when to start braking, and in controlling his ongoing braking. Implications of the theory for safe speeds and safe following distances are discussed, taking into account visual angular velocity detection thresholds, and some suggestions are made as to how safety on the roads might be improved.


Facilitation of stereopsis from a large disparity random-dot stereogram by various monocular features: further findings (a short note). This experiment examined the effects of adding five different kinds of prominent monocular features to a large-disparity random-dot stereogram. It was found that features which enclosed the disparate area produced the shortest initial perception times for fusion. The longer initial perception times for stimuli containing features without this enclosing property are explained in terms of less-helpful guidance of saccadic eye movements prior to the establishment of fusion. Subsequent reductions in perception times for these latter stimuli could be due to perceptual learning within the eye movement control system.


Sensory interaction: vision is modulated by hearing. An irrelevant noise was turned on at various points during a visual reaction-time task. Latencies were reliably smaller than on quiet trials, provided the noise was turned on when a subject was looking at a relevant visual stimulus. This effect occurred regardless of whether the distribution of interstimulus intervals was constant or varied during a session, as well as independently of a subject's base rate of response and level of practice in the task. But it disappeared if reaction times in completely noisy sessions were compared to performances in quiet stimulated by a test form, but not with the particular ear stimulated by a noise. A model is suggested for these and related results in which the arousal elicited by a loud sound in the central nervous system either activates associative memories of form, inhibits early components of striate cortical unit response to the intensive properties of a visual stimulus, or both.


Sun figure: an illusory diffuse contour resulting from an arrangement of dots. A set of black dots grouped on a white background to create an impression of radiating lines which fade towards the centre makes possible a percept of a central glow.


Heparin treatment in severe preeclampsia and glomerulonephritis in pregnancy. Thirty patients have been treated with heparin during pregnancy or in the immediate postpartum period. Twenty had severe preclamptic toxemia. Five presented before 30 weeks and in addition had low estriol levels and high blood ureas. The chance of a successful pregnancy in such patients is very low indeed; however 3 of these 5 patients had living babies. Even in patients presenting after 30 weeks of gestation, if severe preeclampsia is accompanied by low estriol levels and high blood urea levels, the anticipated fetal survival is poor. However, all 5 patients in this group were treated with heparin and had living babies. In the small group of patients with glomerulonephritis, there was a suggestion that heparin treatment may have been of value. Biopsy studies suggested that heparin may help to prevent lesions in arteries and arterioles which have been noted to develop in association with preeclamptic toxemia. In four patients treated in the postpartum period, there was possible benefit in terms of renal function, intravascular coagulation, vessel lesions, and subsequent successful pregnancies.


Maternal uterine vascular lesions in the hypertensive complications of pregnancy. To establich hemochorial placentation, the nonvillous trophoblast breaches the spiral arteries in the basal decidua and later migrates down the arteries as far as the parent radial arteries in the myometrium. Interactions between the endovascular trophoblast and the tissues of the maternal vessel wall (physiological changes) adapt these arteries to the uteroplacental arteries, and these large caliber vessels empty into the intervillous space. Loss of reactive musculoelastic vascular tissue results in a lowering of peripheral resistance, permitting a greatly increased blood flow into the intervillous space. In preeclamptic pregnancies, there is inhibition of the secondary endovascular trophoblast migration in the second trimester, so that the myometrial segments of the uteroplacental arteries remain as responseive musculoelastic arteries. With the onset of clinical preeclampsia, acute atherosis, a necrotizing arteriopathy, affects small muscular arteries in the placental bed and arterioles in the decidua vera. When essential hypertension is complicated by preeclampsia, the placental bed arteries show a combination of hyperplastic arteriosclerosis and acute atherosis. There is evidence that the establishment of hemochorial placentation requires controlled immunological reactions between fetal and maternal tissues and that an inappropriate immune response may be involved in the pathogenesis of the arteriopathy of preeclampsia.


Pregnancy, outcome as related to hypertension, edema, and proteinuria. Clinical variables of blood pressure, proteinuria, edema, and maternal weight have been studied extensively, with particular reference to associated adverse fetal and infant outcomes. The levels of these variables, as well as their relative patterns of change with advancing pregnancy, were investigated by several analytic methods. It was determined that diastolic blood pressure and proteinuria, alone and in combination, profect on fetal and infant outcomes to enable us to create an empirical classification of gravidas whose fetuses were probably at risk. The results must be considered preliminary in view of the fact that the work is still in progress.


The differential diagnosis between preeclamptic toxemia and glomerulonephritis in patients with proteinuria during pregnancy. The renal biopsies from 123 patients who presented with proteinuria during pregnancy have been reviewed. Forty-seven showed glomerulonephritis that could be diagnosed on morphological grounds or on a clear-cut history of urine abnormalities before pregnancy. Fifty of the remaining 76 had been followed after pregnancy. In these 50 patients, a retrospective diagnosis of glomerulonephritis or preeclamptic toxemia was based on the persistence or disappearance of proteinuria and/or hematuria three or more months after pregnancy. Among 22 in whom a biopsy diagnosis of "pure" preeclamptic toxemia had been made, 19 showed disappearance of urine abnormalities after pregnancy, thus confirming the biopsy diagnosis. A retrospective analysis showed focal and segmental glomeris group but none in the preeclamptic toxemia group. Other differences could not be defined without quantitative evaluation; however, the glomeruli appeared to be more cellular in the glomerulonephritis group. The presence of IgA, IgG, IgM, Complement, and fibrin was not of value in distinguishing glomerulonephritis from preeclamptic toxemia.


Soidum requirement of the rat during pregnancy. The sodium requirement for the pregnant rat was established on the basis of a series of studies in which the following parameters were investigated on varying levels of soidum intake: sodium retention, plasma and tissue sodium concentrations, hematocrit, juxtaglomerular index (JGI), zona glomerulosa (ZG) width, ultrastructure of the ZG cell, and aldosterone-producing capacity of the ZG cell. The recommended level of 26 mEq sodium/100 g diet was identified as the level of intake that permitted the pregnant rat to achieve the homeostatic adjustment to sodium need with as little apparent stress on the JGI and ZG as in nonpregnant rats; as a criterion, we used thepoint in the continuum of physiological adjustment where the first recognizable changes in cellular morphology could be identified. These data, along with addtional data on blood pressure and renal medullary lipid concentration, indicate that during pregnancy a chronology of events occurs which suggests a working model for the maintenance of sodium homeostasis and blood pressure regulation.


The effect of estrogens on renal sodium excretion in the dog. The effects of estrogens on electrolyte balances were studied in dogs. In doses of 1 mg or 250 mug/day, 17 beta-estradiol produced moderate sodium retention, whereas 100 mug/day produced only slight sodium retention. Estriol produced about the same degree of sodium retention as did estradiol. The administration of estradiol during the injection of large doses of DOCA produced the same degree of sodium retention as estradiol administered alone. Also, the injection of DOCA to estrogen-treated dogs resulted in a transitory sodium retention, followed by a sodium escape and a return to the previous balance level. Estradiol given to dogs with an arteriovenous shunt that had failed previously to show sodium escape during treatment with DOCA produced the same degree of sodium retention as that observed during estradiol administration to normal dogs. Five adrenalectomized dogs maintained on cortisone and DOCA had normal sodium balances during the control period but showed a retention of sodium during the administration of estradiol; administration. Four adrenalectomized dogs maintained only on cortisone were in negative sodium balance during the control period, but during estradiol treatment they showed a retention of sodium. These studies provide evidence that estrogens promote sodium retention in dogs by mechanisms other than by decreasing the glomerular filtration rate, increasing the secretion rates of adrenal steroids, or affecting the sodium escape mechanism. It is suggested that estrogens might act directly on the renal tubules at receptors other than those for the adrenal mineralocorticoids to produce sodium retention.


Studies of the renin-angiotension-aldosterone system, cortisol, DOC, and ADH in normal and hypertensive pregnancy. Compared with a group of normal pregnant women, matched for age, parity, posture, and length of gestation, women with hypertension and proteinuria in the last trimester had significantly lower plasma concentrations of renin, renin substrate and angiotensin II. Plasma aldosterone and DOC concentrations were also lower in the hypertensive group. The plasma levels of cortisol, corticosterone, and ADH showed no significant difference. Plasma renin concentration was raised throughout normal pregnancy, and part of this increase appeared to be due to the presence of an inactive form of renin. Plasma concentrations of renin substrate, angiotensin II, and aldosterone were also raised in normal pregnant women, but concurrent measurement of these substances showed no significant relationship between them, renin, and plasma electrolytes in mid- or late gestation. A study of five women in the weeks immediately after conception showed increases in plasma angiotensin II and aldosterone concentrations, which were significantly related at this very early stage of pregnancy. Total 24-hour urinary sodium increased gradually from about two weeks after gestation to the end of the study five weeks later. This increase was due mainly to a rise in overnight sodium excretion, with a fall in the day/night ratio. No relationship was found between plasma angiotension II or aldosterone concentrations and day, night, or total 24 hour sodium excretion.


Sequential changes in the renin--angiotensin--aldosterone systems and plasma progesterone concentration in normal and abnormal human pregnancy. To investigate the role of components of the renin-angiotensin-aldosterone system and plasma progesterone concentrations in the pathophysiology of hypertension in pregnancy, sequential measurements were made throughout pregnancy in 45 normotensive subjects, 41 other pregnant patients in whom hypertension became manifest only during pregnancy and 26 patients with chronic hypertension antedating pregnancy. Among the normotensive subjects plasma renin activity and substrate, plasma aldosterone and progesterone concentrations were elevated as early as the sixth week of gestation. While consistent, progressive, further increases were noted in renin substrate, aldosterone and pregesterone concentrations during pregnancy, plasma renin activity did not continue to rise. In both hypertensive groups, plasma renin activity and aldosterone concentration were significantly suppressed during the last trimester despite levels of renin substrate and progesterone that were not significantly different than those observed in normotensive pregnancy. These observations confirm earlier studies reporting suppression near term of plasma renin activity in toxemia and indicate from these prospective observations that they are secondary effects. These studies, in addition, demonstrate parallel suppression of plasma aldosterone concentration in toxemia. The current report also indicates that this suppression is not due to a decrease in renin substrate concentration and that a hypothesized deficiency of plasma progesterone, which was not observed in the hypertensive subjects, does not play a permissive role in the development of hypertension.


Remote prognosis after eclampsia.

Remote prognosis after eclampsia. Of 270 women who survived eclampsia in the period 1931 through  1951, all but three were traced in 1974. In white women having eclampsia as primiparas, neither the remote mortality nor the prevalence of hypertension is increased over that in unselected women matched for age. Both are increased significantly in white women having eclampsia as multiparas and in the 24 black women in the study. The excess of remote deaths among the multiparous eclamptic women is accounted for by the lethal consequences of hypertensive disease. Repeated hypertensive pregnancies after eclampsia are often a sign of latent essential hypertension and may precipitate prematurely a chronic hypertension that is in the making. The prevalence of diabetes of late onset is increased over the expected rate in both primiparous and multiparous eclamptic women. It is concluded that eclampsia is neither a sign of latent hypertensive nor of renal disease, and it does not cause chronic hypertension, whatever the duration of the acute hypertensive phase.


Urinary kallikrein in normal and hypertensive pregnancies. Urinary kallikrein was measured in normal pregnant women stages of gestation and in women who developed hypertension in late pregnancy. Mean urinary kallikrein was highest in the first trimester and fell significantly in the third trimester to nonpregnosterone system. A negative correlation was observed between urinary kallikrein and the length of gestation in normal pregnancy. Urinary kallikrein fell significantly below nonpregnant levels in patients with hypertension while the renal excretion of sodium and water was not different from that in normal pregnancy of the same dy is discussed in the light of factors known to increase kallikrein excretion. It is considered unlikely that this elevation is due to the escape from the sodium-retaining effect of the high aldosterone of pregnancy. It may be due in part to the stimulating effect of raised angiotensin II levels but it is considered most likely to be the effect of a circulating renal vasodilator. The reduced kallikrein in hypertension of pregnancy may play a part in the development of the hypertension and resembles the reduced kallikrein excretion in essential hypertension.


Uteroplacental hemodynamic response to antihypertensive drugs in hypertensive pregnant sheep. The production of renal hypertension by single renal artery constriction in pregnant sheep decreases uteroplacental blood flow. This decrease in uteroplacental perfusion persits for 7-10 days and then returns to normal control levels despite the persistence of hypertension. During hypertension the uteroplacental vascular bed is dependent upon the elevated arterial pressure for perfusion. Therefore, a pharmacologic lowering of this perfusion pressure may reduce uteroplacental blood flow. Antihypertensive agents whose major effect is the lower vascular resistance will tend to reduce uteroplacental blood flow, while those agents which increase cardiac output in addition to lowering the vascular resistance, will tend to maintain or increase uterine blood flow. Of the specific agents tested, hydralazine, which has a positive inotropic and chronotropic effect on the heart, was the only one that consistently increased uteroplacental blood flow. Blockade of these beta-mimetic effects resulted in a fall in uterine blood flow as the perfusion pressure was reduced.


Disseminated intravascular coagulation and experimental disease models in pregnancy. The feeding of a diet containing oxidized lipids and low in vitamin E to pregnant rats induced the generalized Shwartzman reaction. The etiologic factor or factors can be concentrated by molecular distillation of the oxidized lipid. The addition of large amounts of tocopherol prevents the appearance of the disease. Oral administration of antibotics reduces the incidence of the disease by a factor of four. Pathological changes in the placenta consist of degeneration of the trophoblast, thrombosis and fibrin deposition in maternal vascular spaces, congestion of maternal blood spaces, hemorrhage into the uterine cavity, placental separation, intrauterin fetal death, decidual or uterine vein thrombosis, placentitis (10% of the cases), and fetal resorption.


Factors that influence maternal mortality in eclampsia. Three hundred sixty-five cases of eclampsia, including 49 women who died, were analyzed in order to determine factors which led to death. The age of the patient was clearly the most important factor. Older women tended to have coexisting renal and vascular disease and also manifested more hematologic abnormalities, in particular, disseminated intravascular coagulation. Other important factors leading to death were twin pregnancies, delay in hospitalization, failure to terminate the pregnancy, and the physician's unawareness of the severity of the mother's disease. The mortality after cesarean section was the same as in women delivered vaginally.


The rat as a model for preeclampsia.

The rat as a model for preeclampsia. Several methods were used in an attempt to produce preeclampsia in the pregnant rat. Desoxycorticosterone acetate plus increased NaCl intake produced hypertension, proteinuria, rapid weight gain, convulsions, decreased litter size, decreased offspring weight, increased fetal and maternal mortality, and renal lesions similar to those seen in human preeclampsia. Injection of placenta in Freund's adjuvant produced mild blood pressure elevation and proteinuria in the pregnant rat. Rabbit antirat placenta serum produced hypertension in the pregnant rat but not in the nonpregnant rat. Liver congestion and renal glomerular congestion were observed in both pregnant and non-pregnant rats. Pregnancy in the rat reduced hypertension produced by applying a Goldblatt clamp prior to breeding. Uterine ischemia produced by wrapping the uterus in cellophane produced mild blood pressure elevation and proteinuria. A vitamin-E-deficient diet that contained substantial amounts of partially perioxidized, polyunsaturated fatty acids produced morphological lesions in the pregnant rat similar to those seen in human preeclampsia, but hypertension, edema, and proteinuria were absent. None of the maneuvers was effective in producing a complete model of human preeclampsia, but they do provide material for study that could answer somebasic questions about preeclampsia.


Nonhuman primate models of toxemia of pregnancy. Hypertension in the nonpregnant and pregnant nonhuman primate is not found frequently by research investigators. Its incidence is probably infrequent. No well-defined clinical syndrome analogous to toxemia of human pregnancy has been described. The experimental induction of the disease in pregnant nonhuman primates has been difficult. Although there would be an important role for such an animal model, its discovery does not appear imminent.


Proteinuria and the renal lesion in preeclampsia and abruptio placentae. The defect in glomerular permeability that leads to proteinuria can be assessed by determining the relative clearance of macromolecules of known but different dimensions, that is, glomerular selectivity. Such estimates can be made using naturally occurring plasma proteins and dextran or polyvinylpyrrolidone injected into the circulation. In preeclampsia, protein and dextran selectivities show good concordance. The proteinuria is intermediate in its selectivity. These findings confirm that proteinuria is glomerular in origin and that the glomerular abnormality is uniform throughout the majority of functioning glomeruli. In abruptio, protein selectivity is very low and dextran selectivity is high. This pattern is seen also in acute ischemic renal failure and suggests that the true glomerular functional defect is actually less severe than in preeclampsia and that much of the protein in the urine in abruptio is postglomerular in origin. The structural lesion in preeclampsia is "characteristic" only in the sense that a number of individual components of glomerular injury, which are themselves commonly seen in other glomerular disorders, occur in a particular balance, and not because of any single unique or specific feature. The important components--that is, endothelial swelling, mesangial cytoplasmic activity, subendothelial deposits, and occational thrombosis of the afferent arterioles--all occur, albeit to a lesser degree, in abruptio placentae, as well as in other glomerular disorders in which intravascular coagulation is a primary cause or plays a major role.


Selectivity of proteinuria during pregnancy assessed by different methods. Relative protein clearance measurements have gone a long way toward characterizing the nature of pregnancy proteinuria but have failed to distinguish between preeclampsia and primary renal disease. The prognostic significance of different degrees of selectivity has been a source of disagreement in past studies. The polymer clearance studies reported here, using tracer doses of labeled PVP, have demonstrated two forms of proteinuria: a benign form due to a vasoconstrictor effect where fetal outlook is good ("vasoactive"), and a form associated with intravascular coagulation which indicates worse fetal prognosis ("membranous"). Underlying chronic renal damage of minor degree is identifiable with PVP clearance. Concurrent measurements of protein clearance, using smaller-sized proteins than is customary, gave hope for future development of meaningful clinical tests.


The role of coagulation and fibrinolysis in preeclampsia. The coagulation and fibrinolytic systems play a key role in maintaining the integrity and patency of the vascular compartment. Pregnancy induces extensive physiological changes in these systems, thus creating an enhanced capacity to produce fibrin and a diminished ability to remove it. Fibrin deposition localized to the uteroplacental circulation is a feature of normal pregnancy. In women with fatal eclampsia, disseminated intravascular coagulation with fibrin deposition in the renal glomeruli is well documented. The condition of preeclampsia is not well defined. Nonetheless, evidence of intravascular coagulation, as shown by elevated levels of fibrin degradation products and reduced platelet counts, has been found in many women with preeclampsia. Serial studies showed that thrombin generation, as indicated by the ratio of factor VIII-related antigen to factor VIII coagulant activity, is considerably in excess of that which occurs in normal pregnancy, and its appearance coincides with the development of the clinical features of preeclampsia. Heparin therapy has bot been proven of value in established preeclampsia, but this fact does not disprove that role that intravascular coagulation may play in the pathogenesis of the disease. A controlled trial ina high-risk group of low-dose he;arin and an antiplatelet agent from the 16th to the 18th weeks of pregnancy onwards is required to elucidate the role of intravascular coagulation in preeclapmsia and its effect on the fetus.


Does coagulation have a causative role in eclampsia? Alternations in the coagulation mechanism were looked for in a population of eclamptic women, most of when were young, nulliparous, and without evidence of chronic vascular disease, and all of whom survived. Thrombocytopenia was identified in 29% of these women. A prolonged plasma thrombin time was demonstrated in 51% yet elevated fibrinogen-fibrin degradation products in serum were uncommon, as was fibrin monomer in plasma. Overt microangiopathic hemolysis was rare. It is concluded that disseminated intravascular coagulation, when it does occur in eclampsia, is the consequence of the disease rather than the cause. Moreover, endothelial damage, rather contents, probably initiates the thrombocytopenia and other coagulation changes.


Organochlorine insectide residues in vegetables of the Kitakyushu District, Japan--1971-74. The residue levels of organochlorine insecticides BHC, DDT, endrin, and dieldrin in the Kitakyushu District, Japan, were monitored from 1971 to 1974. Agricultural uses of these insecticides were banned in 1970. BHC isomers, alpha, beta, gamma, and delta-BHC were detected in all vegetable samples taken; beta-BHC residue appeared in the highest levels. The proportions of each BHC isomer in total BHC residues were much different from those in the technical product. Average residue levels of alpha, beta, gamma, and delta-BHC, dieldrin, endrin, and DDTR (p,p'-DDE+p,p'-TDE+o,p'-DDT) in 1971 were 0.007, 0.042, 0.010, 0.008, 0.021, 0.010, and 0.041 ppm in radishes, and 0.004, 0.007, 0.009, 0.003, 0.087, 0.031, and 0.009 ppm in cucumbers. Levels found in 1974 were 0.002, 0.003, less than 0.001, less than 0.001, 0.005, 0.006, and less than 0.001 ppm in radishes, and less than 0.001, 0.001, 0.001, less than 0.001, 0.008, 0.009, and undetectable in cucumbers. These residues were translocated form the insecticide-contaminated field soils to the vegetables through therir roots. Residue levels of dieldrin and endrin frequently exceeded the pesticide tolerance limits of Japan, but DDTR residues were only slightly above the specified levels.


Organochlorine pesticide residues in sugarbeet pulps and molasses from 16 states, 1971. Sugarbeet pulp and molasses from 57 processing plants in 16 States were sampled for pesticide residues. No molasses samples contained detectable pesticide residues, but about 15 percent of the pulp samples contained low levels of dieldrin, toxaphene, or DDT and its degradation products. Sugarbeet pulp, when used as animal feed, can be a source of pesticidal contamination of human food.


Pesticide residues in urban soils from 14 United States cities, 1970. Soil in 14 cities was sampled and analyzed for arsenic and chlorinated hydrocarbon pesticide residues. Heavy loads of chlorinated hydrocarbon residues were detected in the soil. In addition to DDT and its metabolites, chlordane, dieldrin, endrin, heptachlor, heptachlor epoxide, and toxaphene were detected. District variation appeared in some residue levels among cities. Pesticide residue levels in urban soils were generally higher than the residue levels detected in cropland soils of the same States.


Residues of quintozene, its contaminants and metabolites in soil, lettuce, and witloof-chicory, Belgium--1969-74. Authors studied contamination of soils used to raise lettuce in greenhouses and witloof-chicory (French endive) in forcing beds. The crops had been treated with the fungicide quintozene; residues detected included quintozene, its technical impurities and metabolites hexachlorobenzene, pentachlorobenzene, pentachloroaniline, and pentachlorothioanisole. Analyses of 72 soil samples indicated that soils remain contaminated with these chemicals one or more years after application. This is attributed to the high persistence of quintozene, its impurities and metabolites, and the almost annual application of the fungicide. Analyses of the crops show that quintozene, hexachlorobenzene, and pentachloroaniline are taken up from contaminated soils, especially by lettuce. Pentachlorothioanisole, although present in the soils, was not detected in the crops.


Occurrence of pesticide residues in four streams draining different land-use areas in Pennsylvania, 1969-71. Samples of water, streambed material, fish, and soil were collected in four small drainage basins in Pennsylvania in 1969-71 and analyzed to determine the concentrations of chlorinated hydrocarbon insecticides. Water samples were also analyzed for phenoxy-acid herbicides. Each basin studied represents a predominant land use: forest, general farms, residential areas, and orchards. All water and fish samples showed pesticide concentrations less than the maximum level recommended by the Public Health Service, U.S. Department of Health, Education, and Welfare. However, no fish were found in the orchard stream. DDT or one of its metabolites was the most frequently occurring insecticide and was detected in all media sampled except the forest soil. The highest combined concentration of DDT and its metabolites in storm-runoff samples was 11.4 mug/liter in a sample collected from the residential area stream, but the median was higher (0.12 mug/liter) in the orchard than in the residential area (0.02 mug/liter). A sample of the top 0.5 inch (13 mm) of orchard soil contained 40,000 mug/kg DDT and its metabolites, even though DDT had not been used in the orchards for several years prior to this study. Maximum concentrations detected in other orchard media are 330 mug/kg in streambed material and 3.45 mug/kg in storm runoff. Dieldrin was the second most frequently occurring insecticide. Other insecticides detected were chlordane, heptachlor epoxide, lindane, and a trace of aldrin in one fish sample. Each stream contained at least one of the following herbicides: 2,4-D, silvex, or 2,4,5-T.


Mercury and 2,4-D levels in wheat and soils from sixteen states, 1969. Mercury and 2,4-D levels were determined for soil and wheat from 16 States. Mercury was detected in all samples; 2,4-D was found in eight percent of the soil samples and six percent of the wheat samples analyzed.


Pesticide levels in hay and soils from nine states, 1971. In 1971 hay and soil samples were collected in 9 States to determine the incidence and levels of pesticide residues in hayfields. Residues were detected in 8 percent of the soil samples and 29 percent of the hay samples. DDT and its metabolites, DDE and TDE, were contained in 2 soil samples and 21 hay samples. Heptachlor epoxide and chlordane were detected in 1 soil sample, dieldrin in 5 soil samples, and diazinon in 4 hay samples.


Organochlorine pesticide residues in plain Chachalacas from South Texas, 1971-72. Plain chachalacas (Ortalis vetula) from the intensively cultivated and sprayed Lower Rio Grande Valley of Texas were analyzed for pesticide residues during 1971 and 1972. Residues of eight organochlorine pesticides and a polychlorinated biphenyl were identified in fat tissues of specimens collected from four study areas. Chemicals detected in all 24 birds and average residue levels (+/- SD) in ppm wet weight were: DDT (1.52 +/- 4.12), DDE (2.48 +/- 2.09), dieldrin (0.23 +/- 0.59), endrin (0.13 +/- 0,52), and Aroclor 1248 (0.17 +/- 0.20). Residue levels varied considerably, but the majority of the fat tissues contained significantly less than 1 ppm of these chemicals. Because birds of this species feed primarily on unsprayed native fruits rather than on sprayed crops, they adsorb very few pesticides through their diet. Although birds from exposed areas near cultivated field had generally higher residues than had birds from less exposed areas, these herbivores generally had much lower residues than would most birds living near heavily treated lands. During the present study there was no evidence that plain chachalacas died as a direct result of exposure to agricultural chemicals, nor was there evidence that eggshells of this species have thinned significantly since 1900.


Insecticide residues on stream sediments in Ontario, Canada. Insecticide residues on suspended and bottom sediments of streams of Ontario, Canada, have been studied in a tobacco-growing and a vegetable muck area. The proportion of TDE to DDT was less than 1 in water and greater than 1 in bottom sediments. The ratio of TDE to DDT in bottom material increased linearly from the contamination point at stream source to the mouth of Big Creek in Norfolk County, Ontario. Bed load samples contained three to six times greater concentrations of insecticides than bottom material. Adsorption of insecticides on suspended sediment decreased in order DDT greater than TDE greater than dieldrin greater than diazinon, which is consistent with the water solubility of these compounds.


Preliminary study of the occurrence and distribution of DDT residues in the Jordan watershed, 1971. Data obtained from the Jordan watershed in 1971 revealed the presence of DDT and its metabolites at various levels along the food chain. Detectable levels of sigmaDDT in water of the Jordan River and two fish ponds ranged from 0.019 to 0.500 ppb, which is 1/10 to 1/500 the maximum level permitted in water by the U.S. Government. Mean residue in phytoplankton was 0.906 mug/g; in zooplankton the mean was 6.49 mug/g. SigmaDDT residue in fish of the Jordan watershed averaged 0.37 mg/kg in carp, 2.59 mg/kg in benith, and 3.34 mg/kg in sardines.


[First aid at medical congresses].

[First aid at medical congresses]. The sixth International Congress of Pharmacology in Helsinki, July 1975, was held on a campus area 5 km from the nearest hospital. The congress was attended by 2 600 active participants and one thousand social members, traveling from 54 countries. The equipment at the Congress first aid station allowed for all kinds of emergency treatments, ranging from the care of minor complaints to cardiopulmonary resuscitation. A mobile intensive care unit was kept outside the station throughout the day and was also available at the major social events in the evening. The great majority of the symptoms necessitating a visit to the station were minor complaints. Most participants received their medication direct from the first aid station, the most common drugs being mild analgesics, anticholinergics and antibiotics. According to our experience, at a congress with 3 500 participants it is sufficient to have one physician present at the first aid station, or at least on call, and one to three additional first aid assistants. In general, it is of utmost importance to make adequate plans for the provision of medical as well as dental care at large congresses.


[Multisite cervico-mediastinal venous samples for radioimmunologic determination of parathormone in primary hyperparathyroidism. Results in 24 surgically confirmed cases]. Multisite cervico-mediastinal venous blood samples were collected fort the estimation of parathormone before operation in twenty four patients subsequently confirmed at surgery to have primary hyperparathyroidism. The examination made it possible to lateralise a single (single adenoma: 18 cases) or predominant lesion (multiple adenomas or hyperplasia: 6 cases), in 15 of them (62%). In patients with a single adenoma, exact lateralisation was obtained in 12 out of 18 cases (9 had selective samples with 7 accurate lateralisations). This lengthy and costly examination is essentially of value in localisation and should be used essentially in patients with virtually definite primary hyperparathyroidism and in whom the responsible lesion has not been discovered at exploratory operation.


[Difficulties in the detection and the diagnosis of carcinoma in situ of the uterine cervix in the presence of associated dysplasia]. Ninety nine cases of carcinoma in situ of the cervix are reported. In all cases, the definitive diagnosis was established after study of an operative specimen (cone biopsy or hysterectomy) examined by serial section. Pre-operative cytology was falsely negative (or suggestive of simple dysplasia) in 35,4 per cent of cases and pre-operative biopsy falsely negative in 40 per cent. These errors were approximately twice as common in cases in which dysplasia was present in association with the caricinoma (40 cases) than in those cases in which the malignancy alone was present (59 cases). The practical conclusions which may be drawn from these findings in relation to detection and diagnosis are discussed.


[Mammotomography, a new technic of breast examination]. The authors present the first results of a new technique of breast examination: tomo-mammography. This new method allows a complete study of the whole gland without any compression and any modification of histological and anatomical structures, and an analysis of the center of breast lesions in which are rassembled the most reliable radiological signs. These first results enable to hope a large increase of possibilities of diagnosis of breast lesions in the most difficult anatomical and clinical cases.


The preleukemic syndrome: clinical and laboratory features, natural course, and management. The clinical and laboratory features of the stages in the evolution of acute nonlymphocytic leukemia are reviewed. Based on a retrospective analysis of 34 patients who died with an acute myelomonoblastic leukemia, the "preleukemic syndrome" has been shown to display a clinical picture sufficiently specific to permit its recognition prospectively (i.e., before the development of overt leukemia). The results to date of a variety of prospective studies are reviewed, and the approach(es) to the management of these cases is considered.


The use of the Robinson in vitro agar culture assay in adult acute leukemia. Previous in vitro classification of adult acute leukemia incorporating morphology has been complex and difficult to understand. We have devised a simplified classification based solely on leukemic proliferation in vitro. Forty-four patients with adult acute leukemia previously untreated were included in this study and received identical chemotherapy. Three in vitro groups were recognized. The complete remission rate (CR) was 77% in the 13 patients with no leukemic growth in vitro (Group 1), 81% in 16 patients with leukemic cell growth but aggregated of 20 cells or less (Group 2) and only 27% in the 15 patients with aggregates of greater than 20 (Group 3). There was a highly significant difference in complete remission rates between Group 3 and the other 2 groups (p less than 0.01). Linear logistic regression analysis demonstrated the independence of the in vitro growth from other prognostic variables. The cause of death in failures suggested that this system detects resistance to the chemotherapy. Similar multifactorial analysis including in vitro agar culture may help to predict for chemotherapy response in preleukemia and leukemia with a low blast cell infiltrate when cytotoxic therapy is clinically indicated.


An approach to human preleukemia using cell culture studies. Cell culture methods applied to the study of acute leukemia have indicated the presence of many abnormalities. Utilizing this knowledge, we have applied cell culture techniques to the evaluation of a patient population with a recognized risk of developing leukemia. We demonstrate that cultural abnormalities present in some patients with sideroblastic anemia are similar to those seen in acute leukemia, and that these perturbations may be shown before leukemia develops. This study suggests that cell culture abnormalities may reflect mechanisms operative in vivo, and preceding the development of overt leukemia.


The cellular distribution of erythrocyte and normoblast A1 and A antigens in normal and preleukemic states. An immunoelectron microscopy study. A1 and A alloantigens were visualized on human erythrocytes and normoblasts by immunoelectron microscopy using peroxidase-coupled antibodies. Specimens were obtained from patients with preleukemia and associated antigen weakening, and from individuals with normal antigen values. Cells were fixed by glutaraldehyde and subsequently reacted with antibodies.


Cell membrane antigens associated with human adult acute leukemia. Cell membrane antigens associated with the blast phase of human acute leukemia are separable from inhibitory proteins and from histocompatibility antigens also present in the membranes. Since these antigens are not detectable in remission or normal white blood cells, they provide a useful marker for identification of cells undergoing carcinomatous changes. Blast antigens from acute lymphatic leukemia (ALL) are also present on early human fetal thymus cells; antigens from both sources produce cell-mediated immune (CMI) responses and are structurally similar. Blast antigens from acute myelocytic leukemia (AML) are not associated with fetal antigens and do not cross react with ALL antigens. ALL cells possess a larger quantity of CMI inhibitory protein than AML cells. The isolation, purification and idenfication of these blast antigens is a step toward their use in studying cultured and cloned subpopulations of cells thought to be associated with pre-leukemia.


Notions about human stem cells.

Notions about human stem cells. From an analysis of the known red cell and granulocytic cell turnover rates in the peripheral blood, absolute bone marrow cellularity of man, mitotic index of human marrow, tritiated thymidine labeling index of human marrow, the proportional distribution of the different cell types in the bone marrow of man and the measured DNA synthesis time of differentiated cell lines in human bone marrow, the flux of stem cells into the differentiated compartment has been calculated. By assuming that the same fraction of committed stem cells of man and mouse are in DNA synthesis, the number of cells in DNA synthesis and the size of the stem cell compartments have been calculated. The calculation gives an abundance of stem cells in human marrow that is much larger than that estimated by in vitro culture techniques. On the basis of the calculations, it is hypothesized that the pool of cells preceding the cytologically differentiated pools may consist of self replicating committed stem cells and differentiated cells undergoing amplification that have not developed cytologic markers characteristics of differentiated cells.


Preleukemic states in the light of the leukemia cytokinetics. On the basis of clonal development of leukemias, the beginning of the true preleukemias should antedate the overt leukemia by at least 37 doubling times (e.g., at least 4 years in the chronic granulocytic leukemia).


The role of lymphoid and haematopoietic target cells in viral lymphomagenesis of C57BL/Ka mice. I. Susceptibility to viral replication. The influence of several parameters on the capacity of C57BL/Ka mouse haematopoietic cells to support replication of the radiation leukemia virus (RadLV) has been examined. Although replication of the virus is strongly thymotropic, the bone marrow and spleen are also susceptible when infection is initiated at birth rather than in adult life. Irradiation transiently restores the susceptibility of adults almost to the neonatal level. Neonatal thymectomy does not diminish the capacity of marrow cells to support virus replication, indicating that the migration of infected thymus cells back to the marrow is not responsible for the observed effect. Bone marrow cells in which viral antigens are no longer detectable yield infectious virus after intrathymic inoculation, suggesting the existence of a cryptic state of virus infection.


Preleukemic states. I. Definition and classification. II. Refractory anemia with an excess of myeloblasts in the bone marrow (smoldering acute leukemia). Approaches to the diagnosis and classification of preleukemic states involving chronic cytopenias are presented and discussed. Diagnosis of these states is facilitated by the identification of anomalies in all the myeloid cell lines (i.e., those derived from the bone marrow). These cellular anomalies may be morphologic, biochemical, or functional in nature or may affect the quantity of cell in each line in the bone marrow and the peripheral blood. Such anomalies may occur alone or may be associated. A tentative classifiction is proposed which is based on one or several of these anomalies. Among the quantitative criteria of classification is a moderate and static excess of myeloblasts and promyelocytes in the bone marrow. Refractory anemia with an excess of myeloblasts (RAEM) in the most frequent of these states. Its main clinical and hematologic features are described. The disease course is quite typical, the mean survival being 20 months; some patients survive for more than 30 months. Acute myeloid leukemia (AML) was the cause of death in less than 28% of cases. Infection in the absence of severe neutropenia was frequent. The relationship between RAEM and AML is disc,ssed, and the individual characteristics of RAEM are emphasized.


Preleukemic states in atomic bomb survivors in Japan. Cytologic and cytogenetic studies were performed on the bone marrow cells in atomic bomb-exposed patients who had prolonged periods of blood disorders with termination of acute leukemia (group I, 6 cases) and without the termination (group II, 6 cases), and survivors who were in apparent good health (group III, 85 cases). All but one patient in group I, who were examined at the preleukemic state, had abnormal clones. In 4 out of 6 of group I patients, morphologic abnormalities of bone marrow cells taken 3-10 years before leukemic development were found, such as giant neutrophils or basophils, binucleated granulocytes or megakaryocytes, and bridge formation of chromatid in metaphases. All patients in group II had stable types of chromosome aberrations. The types of cytologic abnormalities were similar to those in group I, but the frequencies were a little less than those in group I. In group III, 14 persons were found to have stable types of chromosome aberrations, of which 11 persons had apparent but transient clone formations. Cytologic and clinical abnormalities were not observed in the group. The persistent and high percentages of cytologic and cytogenetic abnormalities in patients with prolonged periods of blood disorders, regardless of history of radiation exposure, would suggest a preleukemic state, and also give some clue to the problems of leukemogenesis.


Conformational state of DNA in chromatin subunits. Circular dichroism, melting, and ethidium bromide binding analysis. This study compares some physical properties of DNA in native chromatin and mono-, di-, trinucleosomes obtained after mild micrococcal nuclease digestion. Melting curves and derivatives are shown to be very similar from one sample to another although a shift from 79 to 82 degrees C is observed between the mainly monophasic peak of multimers and chromatin. Careful analysis of the positive band of the circular dichroism spectra shows the appearance of a shoulder at 275nm, the intensity of which increases from the mono- to the di- and trinucleosome. This shoulder is maximum for native chromatin. At the same time binding isotherms of ethidium - bromide are characterized by two highly fluorescent binding sites for all the samples but the product KN of the apparent binding constant of the higher affinity binding sites by the apparent number of those sites increases from the mono- to the di- and trinucleosome. There again the valus is maximum for native chromatin. Such results strongly suggest that the native state of chromatin requires something more than the indefinite repeat of an elementary subunit.


An improved separation procedure for nucleoside monophosphates on polyethyleneimine-(PEI-)cellulose thin layers. A procedure is described for the two-dimensional separation of the 4 major and 16 modified nucleoside-(5') monophosphates on anion-exchange thin layers of polyethyleneimine- (PEI-)cellulose. The method, which is simple and less time-consuming than existing partition chromatographic methods, may be used for the identification of 5'-termini of RNA and RNA fragments.


Detection and identification of minor nucleotides in intact deoxyribonucleic acids by mass spectrometry. A mass spectral method is described for the detection and identification of unusual nucleotide residues present in DNAs. Analysis by this method of intact, underivatized DNA from salmon sperm, calf thymus, mouse L-cells, wheat germ, M. lysodeikticus, E. Coli, and the bacteriophages 0X-174, fd, and lamda, yields diagnostic ions for the four common components of DNA as well as characteristic ions for 5-methyldeoxycytidine residues. The spectrum from T2 DNA contains ions indicative of 5-hydroxymethyldeoxycytidine and 5-methyldoxycytidine components but no ions corresponding to deoxycytidine residues. The DNAs of phages fd and 0X-174 also display ion products indicative of N6-methyldeoxyadenosine residues. Additional series of ions in the spectra of all four bacteriophage DNAs suggest the presence of 5-substituted deoxyuridine residues. The detection method exhibits considerable sensitivity in that amounts of DNA as low as 0.01 A260nm units can be used in the analysis, and thus, the procedure should prove of some value in the detection and location of modified components in specific regions of the various genomes by analysis of the appropriate endonuclease restriction fragments.