[Experiments on the medicamental treatment of the noise-induced cochlear damage. Part I. The effect of dipyridamol and allopurinol on the RMP of the cochlea (guinea pig) after noise (author's transl)]. Dipyridamol has in addition to a coronardilatating effect an ati-thrombotic one too. Moreover it facilitates the release of O2 from haemoglobin by increase of the concentration of 2,3-diphosphoglycerate in the erythrocytes. Allopurinol causes a potential resynthesis of ATP in the cells by inhibition of the metabolism of uric acid. Both substances therefore seemed to be suitable for a medicamental therapy of the noise-induced cochlear damage. The expected favourable effect of Dipyridamol and Allopurinol on the organ of Corti after sound exposure (RMP-measurement before and after exposure to pure tone 120 dB SPL) however had not been confirmed by experiment on animals (guinea pig).


Cochlear microphonics and SDH activity in the hair cells under anoxia. Cochlear microphonics and succinic dehydrogenase (SDH) activity of the hair cells during anoxia were studied in guinea pigs. After injection of the glucose-glucose oxidase mixture into the cerebellomedullary cistern, the deprivation of the oxygen tension in CSF and perilymph was measured in different time courses. In CSF, oxygen tension was reduced to zero within 60 min while in perilymph the maximal reduction was about a half the original level. The cochlear microphonics responded well to the oxygen tension deprivation in the perilymph. SDH activity, particularly in the outer hair cells was quite parallel to the oxygen tension in perilymph and also to the behavior of the cochlear microphonics. The present results indicate a close relationship between the electrophysiological and histochemical findings and that cochlear microphonics represent the function of the outer hair cells only.


[Concerning upbuilding of a tissue-bank for the ent-specialty (author's transl)]. The instrumental equipment of an ENT-tissue-bank is shown. A method of supramaximal deep-freezing is demonstrated, that enables to conserve living tissues and organs for an indefinite space of time.


[Determination of mercury-content of tissues preserved in cialit (author's transl)]. The mercury-tissue-concentrations of implants (structures of the middle ear, bones, cartilage, dura) after preservation in solutions of cialit are mostly independent on preservation conditions, low and seem to be physiological. A positive correlation exists between the weight of the implant and the mercury-tissue concentrations. An enrichment with mercury-ions cannot be stated. The statements do not concern the mercury which is bound on cialit in the implant.


[The corneal reflex stimulated pneumatically (author's transl)]. We describe an apparatus measuring the cornealreflex stimulated pneumatically. The flow of preassurised air in the range of 0.1-1.5 bar is controlled by an electromagnetic switch. The time the valve is open, is variable. The air flow is directed to the cornea of the eye. The blink reflex is recorded by means of the surface electromyogramm and displayed on the screen of a storage scope. The device allows a clean, reproducable and simple measurement of the cornealreflex.


Factors determining the potency of mydriatic drugs in man. 1 The mydriasis resulting from topical application of five atropine-like drugs was measured photographically in man. Drug potency was obtained from log dose-response curves. 2 The in vitro potency of eight cholinoceptor blocking drugs, including those studied in man, was obtained by measuring their affinity constants for binding to the receptors of an isolated preparation of the rabbit sphincter pupillae. Values agreed closely with those obtained for the muscarinic receptors of guinea-pig ileum. 3 In vitro and in vivo potency was compared to obtain a quantitative measure of the relative ease with which drugs gain access to the receptors after topical application. 4 The large differences that occur in the intensity and duration of the mydriatic response to atropine-like drugs is primarily the result of differences in their ability to blcok the receptors. Only with tropicamide does its relatively high accessibility affect its potency in man.


The development of an instrument for monitoring dilatation of the cervix during labour. The measurement of cervical dilatation during labour is of fundamental importance to the obstetrician as it indicates the progress of labour. This paper reviews instruments that have been used to measure cervical dilatation in the past and describes the development of an instrument, originally intended to measure both effacement of the cervix and cervical dilatation, but which, because of technical problems, resulted in an instrument measuring cervical dilatation only. The instrument is non-traumatic, accurate, and easy to apply. As well as the clinical application, the instrument has been found useful in studying mechanism of dilatation. Preliminary results have shown that the cervix opens in an oscillatory manner dictated by the strength and period of uterine contractions. It can even close slightly following a series of weak contractions. Further clinical trials are planned.


Subject cataloging practices in North American medical school libraries. A survey of North American medical school libraries was made to determine current trends in subject cataloging practices. First, responses from 114 of these libraries are recorded and analyzed in the following areas: subject heading authority lists employed; use of the divided versus the dictionary catalog; and the form in which local subject authority files are kept. Then, focusing on 78 libraries that use MeSH in combination with a divided catalog, a further analysis of responses is made concerning issues relating to subject cataloging practices: updating the subject catalog to conform to annual MeSH changes; use of guide cards in the catalog; use of MeSH subheadings; filing conventions; and related issues. An attempt is made to analyze the extent to which these libraries vary from NLM practices. Suggestions are offered for formulating subject cataloging practices for an individual library. Finally, while it is concluded that MeSH and the Current Catalog are useful tools, a more detailed explication of the use of MeSH and NLM cataloging practices would be beneficial.


Inhibition of mammalian polyadenylate polymerase by 2-aza-1,N6-etheno-adenosine triphosphate. 2-Aza-1,N6-etheno-adenosine triphosphate (aza-epsilonATP), a fluorescent analog of adenosine triphosphate, significantly inhibits polyadenylate [poly(A)] polymerase of bovine lymphosarcoma and calf thymus, with 50% inhibition at 200 muM (in the presence of an equal concentration of adenosine triphosphate). Calf thymus RNA polymerases II and III are inhibited 32 and 20%, respectively, by a 3.8-fold excess of aza-epsilonATP; DNA polymerase alpha is not inhibited. The inhibition of poly(A) polymerase by aza-epsilonATP appears to be competitive with adenosine triphosphate; incorporation of aza-epsilonATP is not observed. Polymers of 2-aza 1,N6-etheno-adenosine monophosphate are used as primers, but pootly. 1,N-Etheno-adenosine triphosphate and 9-beta-D-arabinofuranosyladenine triphosphate are poor inhibitors of poly(A) polymerase; adenosine diphosphate is ineffective. Deoxyadenosine triphosphate inhibits to the same extent as aza-epsilonATP, while other naturally occurring nucleotides inhibit poly(A) polymerase to varying degrees, with deoxynucleoside triphosphates more potent than ribonucleoside triphosphates. Inhibition of poly(A) polymerase by naturally occurring nucleoside triphosphates suggests that nucleotides may regulate the enzyme in vivo; inhibition by the fluorescent analog aza-epsilonATP suggests that this compound may be useful in elucidating poly(A) metabolism in both normal and neoplastic cells.


Strokes in children.

Strokes in children. Nine cases have been presented in detail to illustrate some of the varied causes of sudden neurological deficit in childhood: arteriovenous malformation, cryptic hamartoma, berry aneurysm, mycotic aneurysm, intraspinal arteriovenous malformation, brain tumor, migraine, arteritis, and multiple sclerosis. The Boston Children's Hospital experience with aneurysms and intracranial arteriovenous malformation has been summarized. It is noteworthy that a cutaneous hemangioma overlay one cranial and one intraspinal arteriovenous malformation. One small but deep cerebral arteriovenous malformation apparently destroyed itself after its second hemorrhage. Not only have multiple sclerosis and a brain tumor mimicked a vascular lesion, but a series of vascular accidents was misdiagnosed first as multiple sclerosis then as a thalamic tumor. The many possible causes of childhood strokes has been thoroughly cataloged in the Report of the Joint Committee for Stroke Facilities in 1973 (11). Children may be more susceptible to strokes because of congenital abnormalities such as congenital heart disease, hemophilia, and sickle cell anemia, or by diseases which more commonly occur in this age group, such as leukemia. The likelihood of brain abscess in cyanotic congenital heart disease is stressed. Arteriographic studies in our series have been safe; however, there have been reports of probable worsening of symptoms in children with multiple cerebral occlusive lesions in the presence of homocystinuria.


[Dense material observed in pericapillary space of the thyroid of Hashimoto's disease]. An electron microscopic observation was performed on the follicular capillary of thyroid of Hashimoto's disease. Material was the thyroid obtained from a 41-years-old female showing typical features of this disease both clinically and histologically. Some remarkable findings were the presence of multi-layered basement membrane like structure, and the accumulation of dense minute granular materials concerning with long processes of lymphcyte in the widened pericapillary space. From the above-mentioned findings, it was postulated that there was abnormal transport on follicular basement membrane-pericapillary space-endothelial basement membrane system.


[Morphological investigation of the neonatal lung with respiratory distress syndrome which was maximally distended with Somentor 33 and formalin (author's transl)]. The importance of morphological immaturity of the lung in the development of the respiratory distress syndrome was investigated. Atelectatic lungs of newborns were maximally expanded with a mineral oil of low kinematic viscosity (Somentor 33) or 10% Formalin. With this method, surface active forces of peripheral air spaces should not impede expansion of the lungs. 27 lungs of neonates who died of respiratory distress syndrome and 10 lungs of neonates without primary respiratory problems were examined. Following maximal expansion of the lungs with the respiratory distress syndrome show a hypercellular densely cellular tissue of the pulmonary segments, much like glanduloid hyperplasia with small peripheral air spaces and long distances for diffusion of the respiratory gases. The lungs of newborns without respiratory distress syndromes are well alveolar following expansion and show an optimal morphology for gas diffusion. A lack of a surfactant should have significant consequences in small air spaces.


A comparison of the effects of CB-154 and lergotrile mesylate on prolactin and growth hormone secretion in mice. The influence of 2-bromo-alpha-ergocryptine (CB-154) and 2-chloro-6-methyl-ergoline-8beta-acetonitrile methanesulfonate (lergotrile mesylate) on prolactin (PRL) and growth hormone (GH) secretion in mice was investigated. Both drugs inhibited the nursing-induced rise in serum PRL in lactating mice, CB-154 being effective at a somewhat lower dosage than lergotrile mesylate. Both drugs reduced basal concentrations of serum PRL by more than 90% within an hr after administration, but the effect of CB-154 lasted for several hr longer than that of lergotrile mesylate. CB-154 did not change the resting concentrations of GH in mice, but it promoted the induction of GH release by nursing; injection of lergotrile mesylate, on the other hand, seemed to enhance the basal concentrations of GH in lactating mice that were separated from their young for 12 hr. The results show that both drugs can be used successfully for reducing PRL secretion in the mouse.


Arthrography of the knee with fluoroscopic technique. The clinical diagnosis of meniscus lesions is often difficult. The authors have therefore used arthrograpy of the knee with double contrast medium. The fluoroscopic technique used in fifty cases is described. The results obtained are reported and compared with 105 other cases in which arthrography was carried out with standard radiological technique. The diagnostic accuracy for meniscus lesions is very high.


Community control of health services. Dr. Martin Luther King, Jr. Health Center's community management system. This article presents the case of Dr. Martin Luther King Jr. Health Center's unique community management system in which neighborhood workers have been developed to assume managerial responsibilities and are directing the Center. The Martin Luther King Center experience is instructive because the Center was able to achieve significant community control by focusing primarily on the internal dimension of control, namely, management, without experiencing destructive conflicts and the deterioration of health services.


The biliary and urinary excretion and the choleretic effect of ioglycamide in dogs. The biliary and urinary excretion and the choleretic effect of ioglycamide were studied in unanesthetized bile fistula dogs using stepwise increasing infusion rates to obtain multiple steady states. The results are compared with data from previously reported experiments in the same animals using iodoxamate and iodipamide. The rate of biliary excretion and the choleretic effect of ioglycamide are similar to those of iodipamide and iodoxamate. Like iodipamide and iodoxamate, the relation between infusion rate or plasma concentration and biliary excretion or concentration of ioglycamide are hyperbolic and can be fitted to saturation kinetics. Quantitatively, the excretion of ioglycamide and iodipamide are virtually identical. However, for any equimolar infusion rate or plasma concentration, more iodoxamate than ioglycamide is excreted in the bile. Despite the greater biliary excretion of iodoxamate, the maximum biliary concentration of ioglycamide, iodipamide, and iodoxamate is the same at low basal bile flow because the choleretic effects of the three compounds are equal. The data suggest that, theoretically, with any equimolar dose ioglycamide will be identical to iodipamide as a contrast material for intravenous cholangiography, but that iodoxamate may be superior to ioglycamide because more iodoxamate is excreted in the bile. This advantage of iodoxamate might become apparent clinically in patients with high basal bile flow or if smaller doses of the contrast material are used. However, at the presently recommended doses of the two compounds, it is unlikely that the use of ioglycamide for intravenous cholangiography will be any different than iodoxamate.


Cholangiographic excretion studies: a comparison of iodipamide and iodoxamate in the dog. Iodoxamic acid is a new hexaiodinated cholegraphic contrast agent. The methylglucamine salts of iodoxamate and iodipamide were administered to labrador dogs as an intravenous infusion. Bile salts were also infused. The biliary concentration and output of the two agents were compared. Bile flow rate, bile salt concentration and bile salt output with the two agents were also compared. The biliary output of iodoxamate (0.70-0.78 mumol/min/kg) was more than 50% higher than the iodipamide output (0.46 mumol/min/kg). Bile salt output and concentration with iodoxamate infusion were lower than with iodipamide infusion. The bile flow rate was higher with the new agent. The complementary effects of increased contrast output and decreased bile salt output with the new agent led to a significantly higher biliary iodine concentration compared with iodipamide. The results of this study support the suggestion that iodoxamate represents a significant advance in the cholegraphic contrast media field.


Hypergastrinemia in hyperthyroidism.

Hypergastrinemia in hyperthyroidism. Fasting plasma gastrin levels measured by radioimmunoassay were found to be elevated in patients with hyperthyroidism. The intravenous injection of arginine caused an increase of plasma gastrin in hyperthyroid patients as in normal subjects. The elevated gastrin level in patients with hyperthyroidism was significantly lowered after the thyroid function was normalized by treatment.


Effect of renin on extrarenal erythropoietin production. Extracts containing renal erythropoietic factor (REF) and others which contain renin reportedly enhance erythropoietin (Ep) titers in the plasma of hypoxic nephrectomized rats. Studies reported here were designed to elucidate the mechanism by which renin increases Ep production in the anephric rat. Injection of a renal extract containing renin significantly raised the blood pressure of anephric rats, and when it was injected just prior to exposure to hypoxia and 15 hour postnephrectomy, the resultant plasma Ep level exceeded that observed in rats exposed to the same hypoxic conditions immediately postnephrectomy. In contrast rats made hypoxic 15 hours after nephrectomy, but not given renin, had plasma Ep levels which were lower than those of anephric rats made hypoxic immediately postoperatively. When renin was injected immediately after nephrectomy or into normal rats, it failed to stimulate Ep production. When diazoxide was injected with the renin extract into hypoxic nephrectomized rats, the vasopressor effect of renin was abolished for 4 hours, and the plasma Ep levels were significantly lower than those of hypoxic nephrectomized animals injected only with renin, Injection of angiotensin II into anephric, hypoxic rats had an effect comparable to that of renin on extrarenal Ep roduction. REF was not detectable in the renin preparation. These results are best explained by the concept that renin and angiotensin increase extrarenal Ep production by causing vasoconstriction and consequently hypoxia in extrarenal sites of Ep production. Also of interest is the finding that plasma EP levels of rats, injected with renin and made hypoxic 15 hours postnephrectomy, are higher than those previously reported to occur in anephric rats.


Investigation of inner cell mass determination by aggregation of isolated rat inner cell masses with mouse morulae. Inner cell masses (ICMs) dissected from 4 1/2-day rat blastocysts were aggregated with 2 1/2-day mouse morulae. Successful aggregates formed blastocysts in vitro and morphologically normal 5 1/2-day conceptuses in the mouse uterus. Immunofluorescent analysis of these conceptuses revealed that rat cells were only present in the embryonic ectoderm and endoderm and never in the trophectoderm derivatives, although rat trophoblast did develop in the mouse uterus in various control experiments. The single-cell resolution of this technique extends the results obtained from aggregating mouse ICMs with mouse morulae and provides strong evidence that ICM cells, although not overtly differentiated, are determined by the blastocyst stage.


The biphasic effect of organic cations on the excretion of other organic cations. The renal excretion of 14C-choline or 14C-acetylcholine was increased by the infusion of another organic cation at low rates but was decreased by infusion of the same added organic cation at higher rates with the Sperber technique in hens. The range of low rates of infusion was from 1 X 10(-15) to 1 X 10(-8) mol/min. At infusion rates greater than 1 X 10(-8) mol/min, inhibition of tubular excretion was found. At the low infusion rates, thiamine, lysine, quinine, atropine, acetylcholine and methylguanidine were found to increase 14C-choline excretion. The same compounds with the exception of lysine and acetylcholine inhibited 14C-choline excretion at the higher infusion rates. A biphasic effect on 14C-acetylcholine excretion was also observed with added atropine, thiamine and choline over the same infusion range. Increases in 14C-choline excretion occurred during a choline infusion rate that normally produced an excretory tubular maximum for choline whereas increases in 14C-acetylcholine excretion occurred during infusion of tracer amounts of 14C-acetylcholine. The effect of the addition of organic cations was selective for cations since the tubular excretion of organic anions was not affected by the addition of organic cations. The tubular excretion ratio of 14C-thiamine/p-aminohippuric acid increased from 0.25 to 0.95 when the infusion rate of added unlabeled thiamine was increased from 1 X 10(-11) to 1 X 10(-8) mol/min. Enhanced tubular excretion of 14C-thiamine may represent the effect of the increased load of unlabeled thiamine to protect the labeled thiamine from conversion to a nontransportable metabolite. Enhancement of excretion of 14C-choline and 14C-acetyocholine produced by very small amounts of other organic cations may represent either inhibition of tubular reabsorptive transport or induction of tubular excretory transport.


Stereology of parallel, straight, circular cylinders. New stereological formulae are developed to quantify an array of straight, parallel, circular cylinders. The problem arose through the necessity to determine the average length and surface density of the crypts of the large intestine. These crypts or glands have the shape of test tubes.


Improved specimen lighting in ultramicrotomy by painting reflective surfaces on specimen blocks. Specimen lighting of ultramicrotomy can be improved by painting reflective surfaces on the ends of the specimen blocks. A convenient paint for this purpose is the white correction fluid commonly used by secretaries to cover typing errors.


The presentation of three-dimensional reconstructions from serial sections. A simple and effective way is described for showing particular structures in serial sections. By using waterproof inks and acetate sheets supported on a frame immersed in water and illuminated from beneath, the information from up to sixty sections can be easily visualized. This technique is particularly useful for displaying enclosed structures and by a suitable choice of colours enables special emphasis to be given to selected components. The information can be recorded simply through stereo photography.


Antihemophilic factor inhibitors. Management with prothrombin complex concentrates. Prothrombin complex concentrates have been evaluated in the treatment of acute bleeding episodes occurring in 11 hemophilic and two nonhemophilic patients with factor VIII inhibitors. In several of the hemophilic patients, a continued fall in inhibitor levels has been observed coincident with continued use of the concentrate Proplex, and one of these patients is now responsive to factor VIII therapy. The therapeutic effectiveness of prothrombin complex products appears to be related to the presence of small amounts of activated factors or to the continued formation of factor Xa in vivo as a result of the increased levels of prothrombin and factors VII and X. Until high-potency activated products are available, prothrombin concentrates offer an effective means of treating patients with factor VIII inhibitor.


Vasculitis with urticaria, hypocomplementemia, and multiple system involvement. A patient with cutaneous necrotizing vasculitis had chronic urticaria associated with multiple system involvement including arthralgias, glomerulonephritis, myositis, pseudotumor cerebri, and adenopathy. Persistent hypocomplementemia is noted with classic pathway activation. The syndrome recognized in this patient and those few individuals reported previously seems to constitute a distinct category of collagen-vascular disease.


Quantitative urinalysis. Diagnosing urinary tract infection in men. Using a hemocytometer, we determined the number of white blood cells (WBCs) per milliliter in uncentrifuged urine specimens. Uninfected urine usually contained less than or equal to 10(3) WBCs per milliliter, although up to 8 X 10(3) WBCs per milliliter were observed. Infected urine regularly contained greater than 10(4) WBCs per milliliter, and the mean WBC count per millimeter for urine from infected patients was 3.1 X 10(5). The absence of pyuria thus provides strong evidence against the presence of urinary tract infection. Similar results were obtained in patients who had indwelling catheters, suggesting that bacteriuria reflects the presence of infection rather than colonization. Valid data are easily obtainable by quantitative urinalysis of uncentrifuged urine specimens. There are obvious differences in WBCs per milliliter, with little overlap between infected and uninfected urine. This method of analysis should replace traditional means of counting WBCs per visual field in a centrifuged, resuspended urine sediment.


Hazards of phlebotomy in polycythemic patients with cardiovascular disease. Three patients with polycythemia and previous evidence of cardiovascular disease underwent routine phlebotomies. Systolic hypotension followed by ineffective volume replacement with electrolyte solutions developed in all patients after phlebotomy. In two patients acute myocardial infarction and in a third cardiovascular collapse and death were temporally related to the procedure. This experience suggests that phlebotomy in patients with cardiovascular disease should be performed by the slow removal of small volumes of blood under continuous blood pressure monitoring. Effective restoration of the plasma volume with plasma or colloid is essential unless volume overload is present.


Estrogen-containing oral contraceptive agents. A basis for their thrombogenicity. The mechanism whereby estrogen-containing contraceptives facilitate thrombosis is obscure, and published data concerning their effect on antithrombin III are conflicting. Plasma samples were examined for the quantity of antithrombin III and activated factor X (Xa) inhibitory activity among 57 women receiving oral contraceptives and 48 controls. The quantity of antithrombin III in both groups was normal. In contrast, Xa inhibitory activity was significantly reduced (P less than .001) among patients taking oral contraceptives, compared to controls. Heparin sodium added to plasma from patients taking contraceptives raised Xa inhibitory activity toward or above normal without changing the quantity of antithrombin III. The effect of estrogen is not to decrease the quantity of plasma antithrombin III, but rather to diminish plasma Xa inhibitory activity, an effect that can be abolished by heparin.


Pleural effusion. A diagnostic dilemma.

Pleural effusion. A diagnostic dilemma. The cause of pleural effusion in 108 of 133 patients was determined by laboratory tests and clinical examination; it was indeterminate in 25, even after complete diagnostic evaluation. In 164 diagnostic thoracenteses, 136 cytologic examinations were done; the results were positive for cancer in 20 (15%). Five of 19 patients (26%) with bronchogenic cancer, 13 of 25 (52%) with metastatic cancer of the lung, and two of 20 (10%) with lymphoma had positive results on cytologic examination. Of 143 routine bacterial cultures, only five were positive (3%). Of 103 mycobacterial and 76 fungal cultures, only one was positive in each instance. Despite the high incidence of indeterminate diagnoses, we recommend that only measurement of protein content and cytologic examination be ordered routinely. Our algorithm provides a logical, cost-effective approach to the diagnostic problem of pleural effusion.


Skeletal and soft tissue sarcomas. Treatment with adjuvant immunotherapy. Because there is evidence for an active immunologic response against sarcoma, a clinical trial of adjuvant immunotherapy using bacillus Calmette-Guérin (BCG) and tumor cell vaccine was begun. Eleven of 18 patients with localized soft tissue sarcoma who received immunotherapy are free of disease, compared to only 5 of 15 treated by operation alone who are free of disease. Furthermore, immunotherapy also prolonged the median disease-free interval from 7.3 months to 15 months in the patients who experienced recurrence of their disease.


Handguns and homicide. A public health problem. Homicide by handgun is a public health problem. No public health-oriented attempts at prevention have been made. A poll of physicians showed strong opinion (1) favoring more stringent controls on the availability of handguns and (2) supporting direct expression of opinion on this issue by physicians within the framework of organized medicine. Physicians can fulfill an obligation to their patients by formulating policy within organized medicine on the handgun issue.


Primary carcinoids of the ileum and rectum. A simultaneous occurrence. A patient had a simultaneous occurrence of an ileal and a rectal carcinoid. The ileal carcinoid, occurring in an area derived from primitive midgut, was argentaffin-positive; the rectal carcinoid, occurring in an area derived from primitive hindgut, was argentaffin-negative. To my knowledge, this is the first reported case of simultaneous ileum and rectal carcinoids; its uniqueness tends to support the concept of heterogeneity of origin of carcinoids in embryologically distinct regions.


Recurrent supraventricular tachycardia. Success and subsequent failure of termination by implanted endocardial pacemaker. After repeatedly establishing the efficacy of competitive premature atrial and ventricular stimuli in terminating supraventricular tachycardia (SVT) in a patient with recurrent and refractory SVT, a permanent right ventricular endocardial demand generator set at 81 beats per minute was implanted. During the subsequent months, many tachycardic episodes, ranging between 160 to 185 beats per minute, were promptly terminated by activating the pacemaker unit with an external magnet and competitively pacing the right ventricle. However, 16 months after implantation, magnetically induced ventricular capture failed to control the SVT. Magnetically induced competitive pacing in SVT should be reserved for the most intractable and refractory cases.


Neurosyphilis and penicillin levels in cerebrospinal fluid. Because neurosyphilis may progress despite therapy with the recommended penicillin regimens, 15 subjects with positive tests for syphilis in the serum and cerebrospinal fluid (CSF) were studied. All of these patients had CSF pleocytosis. Two received penicillin G (5 and 10 million units per day intravenously, respectively) and 13 received benzathine penicillin G, 3.6 million units per week intramuscularly; treatment lasted four weeks. During intravenous and after intramuscular penicillin therapy, a spinal tap was performed on all subjects; later, assays were done. Of two patients who received intravenous penicillin G, one had 0.3 mug/ml and the other had 2.4 mug/ml penicillin in the CSF. Twelve of 13 patients who received benzathine penicillin G had no detectable penicillin in the CSF; one patient had 0.1 mug/ml penicillin in the CSF.


Sauna-takers disease. Hypersensitivity pneumonitis due to contaminated water in a home sauna. Daily saunas taken by a young man were followed by fever, chills, malaise, dyspnea, cough, and myalgia from six to eight hours later. Symptoms, which were related to pouring water from a sauna bucket over the heating element, progressed to chronic dyspnea and fatigue. Serial serum samples showed precipitin reactions to bucket water and extracts of bucket mold. IgG antibody activity, demonstrated by radioimmunoassay, suggested that Pullularia was a major antigen.


Mucocutaneous lymph node syndrome.

Mucocutaneous lymph node syndrome. Mucocutaneous lymph node syndrome represents a series of clinical findings that has been observed primarily in Japanese children. The disease now appears to be migrating to this country. It involves the cervical lymph nodes, the skin, and mucus membranes. Although the course is usually benign and self-limiting, a number of deaths have resulted from coronary artery disease.


Intestinal bypass surgery for morbid obesity. Long-term results. Since 1962, jejunoileal bypass has been performed on 59 male and 171 female subjects, aged 18 to 55 years; these patients were followed clinically. Postoperative weight loss at two years averaged 37% in men and 35% in women. Hypokalemia (23%), hypocalcemia (22%), hypoalbuminemia (9%), metabolic acidosis (14%), elevated liver enzyme values (41%), and hyperbilirubinemia (6%), were the most commonly encountered blood chemical alterations. Complications were arthritis syndrome (men, 8%; women, 19%). urinary calculi (men, 24%; women, 10%), cholelithiasis (men, 10%; women, 9%), liver impairment (men, 2%; women, 6%), and major emotional upset (men, 8%; women, 9%). Forty-nine percent of the men and 51% of the women required rehospitalization for management of complications, surgery for hernia, anorectal disorders, nutritional support, and metabolic study. There were 19 bypass-related deaths (8%), including 10 due to liver failure.


Hepatitis B surface antigen carrier state in neonates. Prophylaxis with large doses of conventional immune human serum globulin. Acute type B viral hepatitis developed near the term of pregnancy in seven women. All had signs of acute hepatitis at delivery, and hepatitis B surface antigenemia persisted two to four weeks after delivery. Two milliliters of conventional immune human serum globulin was administered to the neonates within a week of birth, after preexisting type B viral hepatitis infection was excluded. The antibody against hepatitis B surface antigen (anti-HBs) content of two of the administered batches of immune human serum globulin was 1:32 and 1:64. None of the babies became hepatitis B surface antigen carriers, and anti-HBs developed without obvious clinical hepatitis in one baby. Conventional immune human serum globulin in larger doses may be a relatively safe and effective prophylaxis against the development of hepatitis B surface antigen carrier state even if the anti-HBs content in the administered dose is relatively small.


HLA patterns and disease associations.

HLA patterns and disease associations. The a priori biologic significance of the histocompatibility complex with its excessive polymorphism remains unknown. Teleologically, however, the role of the HLA system may be viewed as vital for survival of the species and the individual by providing the host with a recognition system of and defenses against viruses, microorganisms, parasites, plant antigens, neoplastic cells, and others. HLA testing, in addition to its usefulness in donor selection for transplantation, has been recently applied to the diagnosis and differentiation of specific diseases, the prediction of disease development (risk prediction), and as a basis for prognostic evaluations. An increasing number of diseases is being shown to be linked by specific HLA antigens and certain common denominators, such as arthritides, autoimmune components or infections, suggesting common etiologic or pathogenic mechanisms or both. These diseases with HLA associations can be separated into those that appear certain, probable, or only statistically possible.


The cancer mortality scare. Problems of estimation using monthly data. Considerable attention has been given recently to an apparent 5.2% rise in cancer mortality, based on data for the first seven months of 1975 as reported to the National Center for Health Statistics (NCHS). Later data disclosed that the rise in crude total cancer mortality, while greater than in any recent year, is less than half of the 5.2% originally reported, and the rise in age-adjusted total cancer mortality, while less than 1%, is also higher than the average annual increase from 1968 to 1974. The Monthly Vital Statistics Report provides death rates not standardized for age, race, and sex, and does not include information for specific cancer sites. Therefore, although information in the Monthly Vital Statistics Report is useful for detecting sudden increases in mortality from acute epidemics, it is not appropriate for forecasting trends in cancer mortality.


Lymphangiomatosis with splenic involvement. Severe splenomegaly and anemia developed in a 5-year-old girl with diffuse lymphangiomatosis of the upper part of the body. Radioisotope scanning and celiac angiography demonstrated lymphangiomatosis of the spleen, a rare but diagnosable condition. Intractable infection in areas of ulcerated skin led to her death from overwhelming sepsis.


Early experience with total knee arthroplasty. Early results of 76 geometric total knee replacements were reviewed with assistance from computer analysis. A 92% patient follow-up for one to three years showed an overall satisfactory result with substantial improvement, especially in relief of severe pain. However, several problems are noted, including fractures beneath the tibial plateau and loosening. The long-term results are still unknown. The indications for total knee replacements should remain conservative until long-term results and experience have been achieved.


Nosocomial pseudobacteremia. Positive blood cultures due to contaminated benzalkonium antiseptic. Pseudomonas cepacia or Enterobacter species or both were isolated from blood cultures of 79 patients in a community hospital between April 1971 and March 1972. No common exposures other than venipuncture correlated with positive blood cultures. Pseudomonas cepacia, Enterobacter, and other Gram-negative enteric bacteria were cultured from aqueous benzalkonium chloride used for skin antisepsis prior to ordinary and blood culture venipuncture. Contamination of blood cultures by organisms from the antiseptic most likely accounted for positive cultures in 35 to 38 patients (92%) with P cepacia. The remaining three patients had repeated blood cultures positive for P cepacia and circumstantial clinical evidence of bacteremia; they may have contracted disease through exposure to the contaminated antiseptic. Substitution of an iodine-alcohol antiseptic abruptly reduced the isolation of P cepacia and Enterobacter.


Contaminated aqueous benzalkonium chloride. An unnecessary hospital infection hazard. During January and February 1975, nine patients on a single ward of a rural Tennessee hospital unexpectedly developed sepsis. The aseptic technique employed in the management of intravenous infusions was implicated. Pseudomonas cepacia was recovered from the following: bloodstream, inuse intravenous infusions and the antiseptic, aqueous benzalkonium chloride. The outbreak again calls attention to the infection risk associated with the use of this product. Selection of less hazardous antiseptics and disinfectants is strongly recommended.


Extreme pyrexia.

Extreme pyrexia. Twenty-eight cases of extreme pyrexia seen in a five-year period were analyzed retrospectively. All of the patients had temperatures between 41.1 C (106 F) and 42.2 C (108 F) with a mean maximum temperature of 41.4 C (106.6 F). Infection, thermoregulatory defects, or a combination thereof accounted for fever in these patients. There was little evidence of direct tissue damage caused by fever, and standard therapy with aspirin or acetaminophen, vigorous surface cooling, and volume expansion was generally sucessful. Mortality could be related to the extreme pyrexia in only 7% (2) but an additional 21% (6) of these patients later died from serious underlying diseases.


Neuroleptic-induced akathisia and dystonia triggered by alcohol. Subclinical extrapyramidal symptoms caused by phenothiazine or butyrophenone derivatives can become manifest during and shortly after the consumption of alcohol. Alcohol appears to lower the threshold of resistance to neurotoxic side effects of previously established neuroleptic drugs. Abstinence from alcohol should be routine advice during neuroleptic psychopharmacotherapy.


Aortoduodenal fistula. Primary repair with saphenous vein patch graft. A successful primary repair of a fistula between the proximal aortic suture line and duodenum was performed in a 47-year-old man with the use of a saphenous vein patch graft with omental interposition between the aortic repair and the duodenum. Massive local and parenteral antibiotics were given. The patient remains completely well 3 1/2 years later.


A puzzling case of giardiasis.

A puzzling case of giardiasis. A serious case of infection by Giardia lamblia was difficult to diagnose.


Resuscitation equipment board for nurseries and delivery rooms. A resuscitation equipment board for mounting in delivery rooms and nurseries facilitates orderly and effective resuscitation of asphyxiated neonates.


Lactulose (cephulac) in portosystemic encephalopathy. Lactulose is a synthetic disaccharide that lowers elevated blood ammonia levels and improves symptoms in patients with portosystemic encephalopathy. It is generally well tolerated and appears to be a suitable alternative to neomycin sulfate for maintenance therapy to prevent recurrent attacks and to improve protein tolerance.


[Objective determination of the consensual accommodation (author's transl)]. The direct and consensual accommodation of both eyes were determined by a modified coincidence refractometer. Young individuals with normal monocular and binocular vision revealed a close quantitative correspondence between the direct and the ipsi- and contralateral consensual accommodation. Experimental impairment of the function of the ciliary muscle by medical means caused disturbed consensual accommodation of both eyes. The weakening of the function of the ciliary muscle of one eye by instillation of, for example Homatropin leads to an important increase of the contralateral and diminution of the ipsilateral consensual accommodation. By the results of the investigations it was concluded: 1. that the regulation of the direct accommodation reflex is influenced also by the function of the ciliary muscle in the fixating eye and has stimulating and depressing components, 2. that the innervation of the nonfixating eye passes through an efferent neuron, from where the accommodation impulse emerges to both eyes. - The anatomically based relation between the direct and the ipsilateral and contralateral consensual accommodation allows one to use its quantitative determination in both eyes as a diagnostic test in afferent and efferent disturbances of the accommodation reflex.


Propranolol effect on plasma glucose, free fatty acid, insulin, and growth hormone in Graves' disease. A 3-hr glucose tolerance test was performed in 12 thyrotoxic patients before and after propranolol treatment for 30 days (120 mg/day). Plasma glucose, free fatty acid, insulin, and growth hormone levels were determined on each test and compared to each other and against nine clinically healthy volunteers. In eight thyrotoxic patients (subgroup A) an improvement in carbohydrate tolerance was observed after propranolol treatment, along with a fall in the previously elevated fasting FFA; no change in plasma insulin levels was observed. Plasma growth hormone levels were higher than normal both before and after propranolol; however, a 46% glucose-induced suppression was seen in both instances. In the other four patients (subgroup B) (who had had a marked and rapid weight loss) a deterioration of the previously normal glucosnificant changes in insulin levels. Elevated fasting plasma free fatty acids remained so despite propranolol treatment. Plasma growth hormone was higher than normal before and after propranolol; a late suppression (at 120 min) and no suppression at all were seen, respectively. After propranolol treatment, subgroup B had higher plasma free fatty acid than subgroup A in the fasting state and at 30 and 180 min. It is proposed that the improvement or deterioration in carbohydrate tolerance after propranolol treatment might be related to whether or not a satisfactory propranolol-induced lipolytic blockade is achieved, leading to a decrease in plasma free fatty acid levels, improved insulin sensitivity, and better peripheral glucose utilization. Therefore, a uniform dose of propranolol will not always be sufficient to obtain adequate lipolytic blockade, particularly if the thyrotoxic patient has had a marked and rapid weight loss.


Gastrointestinal milk allergy in childhood: a rational approach. Nine children with "unequivocal symptoms attributable to cow's milk allergy" were referred for assessment. Detailed gastrointestinal and immunoallergic investigations confirmed this diagnosis in only one case. In three of the children an abnormality of sucrose absorption was detected by disaccharidase assay. The results of this study indicate the need for cow's milk provocation under controlled conditions before the diagnosis of gastrointestinal cow's milk allergy can be made. A protocol for the assessment of children with suspected cow's milk allergy is proposed.


The value of gallium-67 scanning in upper abdominal lymphomas. A series of 77 gallium-67 citrate (67Ga citrate) scans of the abdomen revealed lymphoma in 12 cases (nine of non-Hodgkin's lymphoma, three of Hodgkin's disease). Scanning was undertaken (i) to confirm the suspicion of lymphoma, or (ii) as part of a staging procedure when the diagnosis of lymphoma had been established, or (iii) as a follow-up investigation after treatment of lymphoma. The diagnosis of lymphoma in the upper part of the abdomen is difficult with conventional techniques such as lymphography, and it is in this area that 67Ga citrate scanning is shown to be of value.


Uptake of 1-beta-D-arabinofuranosylcytosine and prednisolone by synchronized human lymphoma cells. The cytotoxicity of many antitumor agents exhibits cell-cycle phase specificity. Using a human lymphoma cell line synchronized by thymidine block, we have investigated the differential uptake of radioactive 1-beta-D-arabinofuranosylcytosine (ara-C) and prednisolone in various phases of the cycle. Uptake of ara-C is highest during early S and declines steadily throughout the rest of the cycle. In comparison, prednisolone demonstrates no significant age-dependent difference in uptake although its cytotoxicity is cell cycle sensitive.


Treatment of parkinson's disease with bromocriptine. Bromocriptine in high doses (up to 100 mg per day) was administered to 14 patients with advanced Parkinson's disease whose disorder was progressing despite optimum treatment with levodopa combined with a peripheral dopa decarboxylase inhibitor (carbidopa). In 10, bromocriptine (mean dose, 57 mg) induced a statistically significant (P less than 0.01) improvement in rigidity, tremor, bradykinesia, gait disturbance and total score. In seven patients levodopa with carbidopa was completely replaced by bromocriptine (mean dose, 70 mg), with improvement in four. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance (on-off effect) were decreased whereas orthostatic hypotension and mental changes were increased. Bromocriptine appears to be a major new agent in Parkinson's disease that is especially promising in patients no longer responding to levodopa.


Iron sufficiency in breast-fed infants and the availability of iron from human milk. Four infants were studied who had been exclusively breast-fed for periods varying from 8 to 18 months. All had grown sufficiently to have exhausted their prenatally acquired iron endowment with respect to meeting current needs for maintaining normal hemoglobin levels. All infants had normal hemoglobin values and normal serum iron values. Studies of iron absorption from breast milk and cow's milk were performed in ten normal adults. The absorption of iron from the human milk was significantly higher. These findings suggest that the iron present in human milk is sufficient to meet the iron requirements of the exclusively breast-fed infant until he approximately triples his birthweight.


[Severe hyperosmolarity caused by dietary error in the newborn. A disorder of particular concern in migrants]. Hyperosmolarity as a result of dietary error is a fairly common condition. It is more grave than "thirst fever", the benign reputation of which should not be taken too lightly. The consequences may be serious: death or sequelae related to vascular thrombosis or cerebral lesions. Prevention should be possible in most instances as long as obstetricians, paediatricians, midwives and nursery nurses are aware of the danger of overconcentrated milk formula. Its treatment remains fraught with hazard.


Discoid medial meniscus.

Discoid medial meniscus. Three cases of discoid medical menisci were diagnosed preoperatively by arthrography. Discoid mensiscus usually occurs on the lateral side of the knee; its pathogenesis is obscure.


Interference of bronchographic agents with lung surfactant. Dionosil Oily (a suspension of propyliodone crystals in peanut oil and powdered tantalum were introduced into the right principal bronchi of rabbit lungs. The left lungs were used as controls. Pressure-volume characteristics of excised lungs with Dionosil Oily or peanut oil demonstrated significantly reduced compliance on inflation at a pressure of 3-4 cm H2O. These lungs also retained less air on deflation and therefore demonstrated a significantly reduced stability index. Histological sections revealed microatelectasis closely associated with crystals and/or peanut oil. Lungs with tantalum powder were not measurably influenced by the bronchographic agents. Surface balance experiments with lung surfactant and synthetic dipalmitoyl phosphatidylcholine (DPPC) demonstrated an increased minimum surface tension due to the oil suspension of propyliodone, peanut oil and particles (propyliodone and tantalum). There is good evidence that the oil suspension of propyliodone reduced the surface activity of lung surfactant in situ. Particles also may prevent the minimum surface tension from reaching relatively low values if they enter the alveoli in sufficient quantities.


[Process optimization in the food industry (author's transl)]. Different optimization methods are presented (EVOP, Marginal Analysis, ...) as an example of problem approach and resolution in the food industry. Optimal criteria are presented for experiments design and analysis and mathematical models development for process simulation and optimization.


[Contribution to the study of some factors affecting semolina quality (author's transl)]. In order to identify certain chemical characteristics of semolina that might provide "a priori" information about its pasta making quality, their relationship to pasta cooking chatacteristics were analyzed. The correlation analysis gave significant values for the relationship between semolina reactive SH content and pasta resistance to disintegration and between urea dispersible protein protein content of semolina and pasta volume increase on cooking. The results obtained suggest that possibility of considering separately the results of the various pasta cooking tests in order to express a conclusive quality evaluation.


[Retention of volatile organic compounds in a freeze-dried model food gel (author's transl)]. In this work the results obtained during freeze-drying of a food model gel are reported. The model system was constituted by 12,5% sucrose, 2,5% pectin and five organic volatile substances: acetone, ethyl acetate, methanol, ethanol and n-propanol. In particular, it was studied the effect of granulation and the effect of frozen material thickness on retention of volatiles. Other experiments were made to study volatiles distribution inside the freeze-dried materials; the stripping action of warm air and of water vapor flux through the freeze-dried layers, and eventually the holding capacity of dried layers to "capture" the volatiles. All the data suggested a theory about the different mechanisms which influence the retention and the remotion of volatiles during freeze-drying of foods.


[Copper contamination of Italian tomato products (author's transl)]. This study reports the results of analysis concerning some chemical characteristics of 63 samples of tomato juice and paste. Copper was determined by atomic absorption spectrometry and its average content was 32 ppm. This is not a critical value for human health and results below the upper limit provided by law of several european and not european countries.


[The determination of lead in musts, wines and vinegars (author's transl)]. A method is described for the determination of lead in musts, wines and vinegars by atomic absorption spectroscopy. The method, already proposed as an official method both in Italy and at the O.I.V., gives sufficiently accurate and reproducible results and is particularly suitable for routine analysis. It has been tested on 120 white and red italian wines and has shown that lead pollution in wines has not reached dangerous limits.


[Analytical method to identify and quantitate residues of aromatic polychlorinated hydrocarbons (author's transl)]. A analytical method to identify and quantitate residues of polychlorinated biphenyls, polychlorinated terphenyls, polychorinated naphtalenes and some chlorinated pesticides is described. These contaminants can be recovered from foods or other materials: a silicic acid coloumn chromatografic method previously developed is used to separate PCB's, PCT's, PCN's from organochlorinated pesticide residues. The PCB's, PCT's, PCN's residues identification and their subsequent quantitation can be achieved by conversion into well defined single perchloro-derivatives, viz decachlorobiphenyl, o.m.p. tetradecachloroterphenils and octachloronaftalene, detactable by GLC-EC. The reagnet of exhaustive chlorination of PCB's and PCT's residues is SbCl5, while the reagent used for the exhaustive chlorination of PCN's residues is SO2Cl2 with powdered anhydrous AlCl3 as a catalyst. The identity of perchloroderivatives obtained by chlorination of PCB's, PCT's, PCN's standard mixtures is confirmed on comparing their infrared spectra with the spectra of high purity standards.


[The liquid scintillation counting of the 14C natural level in ethanol: a comparison of different standardisation methods (author's transl)]. The influence on liquid scintillation counting efficiency of internal standards toluene-14C, hexadecane-14C and ethanol-14C has been studied for low level-14C measuring of ethanol samples. Many biological and synthetic samples of ethanol have been counted: the best results are obtained with external standardisation on quenching calibration curve made with ethanol-14C. External standardisation on quenching calibration curve made with toluene-14C is preferable to internal standardisation with ethanol-14C. Hesadecane-14C as internal standard gives activities rather higher than true values.


[Tyndalization by gamma rays. Preliminary esperiments on grape]. The analysis of rot in two grape cultivars ("Moscato bianco" and "Favorita") has shown that the most effective gamma rays dose which pasteurizes fruit pulp with little or no damages is about 180-200 Kr. if administered divided into three fractions, the irradiated sample is less affected by infections (P = 0.01) then the 100 Kr or control samples. On the opposite, no difference between various doses could be detected when gamma rays are administered all at once.


[Recent advances on the "active" vitamin D: 1alpha,25-dihydroxicholecalciferol (author's transl)]. The researches on the mode of action of vitamin D have shown that vitamin D3 in animals is not utilized as such but after Hydrosylation of carbon 25 in the liver and of carbon 1 in the kidney. 1alpha,25-dihdroxycholecalciferol (1alpha,25-(OH)2D3) is the active on two target organis the intestin and bones, acting as a steroid hormone. In the intestin it controls the syntesis of a specific calcium binding protein (CaPB) responsable for calcium absorption. At the bone level it act on the deposition of calcium salts, and whenever necessary on its mobilization. Therefore 1alpha,25(OH)2D3 is active part of the calcium homeostatic system in the organism together with specific hormones such as parathyroid hormone and calcitonin.


[Therapy of supraventricular arrhythmias with a cardioselective beta-receptor blocker (tolamolol)]. In order to evaluate the effect of a new cardioselective beta-blocker (tolamolol) on supraventricular tachyarrhythmias, 10-30 mg of tolamolol was administered on 38 occasions to 35 patients. It is concluded that tolamolol reduces ventricular rate in supraventricular tachyarrhythmias and is often effective in converting paroxysmal atrial fibrillation to sinus rhythm.


[The resistance to antibiotics and chemotherapeutics in bacteria (author's transl)]. Many people today, in agricolture, zootechny and animal feeding, operate with antibiotics and chemotherapeutics. Not all perhaps, know the inconveniences that the large and uncontrolled use of these substances may cause first of all the emergency of bacteria strains resistant to these drugs. We have devoted our attention particularly to the modalities of establishment of the phenomenon: to its incidence and variability in nature, to its transferability and, at least, to its biochemical aspects.


[Study of piruvic acid pool as indirect index of microbial count in foods and beverages (author's transl)]. The quantities are given of pyruvate in a medium to remark any possible connection between varieties of pyruvate and present bacterial flora concentration. We found some connection between the two experiments, even though, not always are very easily to menage.


[The colorimetry of fruits and vegetables (author's transl)]. The colorimetry of food has advanced during last years very much, due to the improving of the equipment and has solved several theoretical and practical problems for the food utilization. In the present paper are reviewed the procedures adopted and the results obtained for the objective evaluation of the colour of processed fruits and vegetables. These results have pointed out the importance of colorimetry in this field and outlined the future trends of the research.


Management of haemophilia in Sweden.

Management of haemophilia in Sweden. The incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophila B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40% have severe, 18% moderate, and 42% mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B. There are 2 main Haemophilia Centres (Stockholm, Malmö) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction I-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Suffcient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 millino units of factor IX are given per year. Treatment is free of charge. Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4-18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40-50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.


[Content of mercury and other elements in samples of canned tunafish (author's transl)]. On the basis of the several studies recently published on the concentration of Hg and other heavy elements in seafish and especially tunafish a work as been carried out to determine the intake due to canned tunafish for the italian population. Instrumental activation analysis has been applied to tunafish canned samples avaible on the market in Rome. The following trace elements have been measured: Cr, Se, Hg, Cs, Fe, Zn, Co, Sb. The intake of Hg and other elements through the canned tuna foods have been evaluated on the basis of the production of such foods in Italy. The tunafish contribution to the total trace elements intakes has been determined by comparing the trace elements concentrations in the canned tunafish with those referred to diets that are representative for the italian population. The results obtained have demonstrated that the trace elements  intake through the diet is not significantly influenced by the tunacanned foods intake.


Management of haemophilia in Greece.

Management of haemophilia in Greece. A short review is given on several aspects of the management of haemophilia in Greece. A total number of 429 patients with congenital haemorrhagic disorders has been registered. The incidence of F. VIII deficiency is 85.9% and that of F. IX 12.9%. Information concerning distribution throughout the country, age, social standard, financial position and education is given too. Haemophiliacs are systematically treated by Athens specialized Haemophilia Treatment Centres. The most widely therapeutic material still used, is fresh frozen plasma. Lyophilized cryoprecipitate and F. IX (prothrombincomplex) concentrate are also prepared but they are not for every day use. Imported concentrates are used only for very serious cases. Home therapy is attempted in limited scale and it is largely discussed. Consultation, out-patients treatment and hospitalization, if needed, are free of charge for haemophiliacs regardless of their financial position or their national insurance.


Hemophilia care in Italy.

Hemophilia care in Italy. Twenty specialized centres for the care of hemophilia and allied disorders have now been established in Italy. Their geographic distribution is uneven and the number is considered inadequate. Financial support is provided by regional Health Departments or by University and General Hospitals; a bill recognizing hemophilia as a social disease entitles the centres to an annual grant from the State or Regional Boards. Less than half of factor VIII employed in the management of hemophilia A is supplied as a cryoprecipitate from hospital blood banks; the rest is imported from commercial manufacturers who also satisfy all the demand for prothrombin complex concentrates. Commercial freeze-dried concentrates can also be obtained free of charge at pharmacies by hemophiliacs covered by national social security schemes. This arrangement facilitates home treatment, which appears the ideal form of management in a country with the geographical features of Italy. In Lombardy, a bill allows hemophiliacs or their relatives to give infusions after adequate instruction. All this has been a great help in achieving more modern management of hemophilia; however, dependence on imported commercial concentrates appears unreasonable on a long-term basis, and major efforts should be directed towards developing a national program for manufacturing blood components.


Management of hemophilia in Spain.

Management of hemophilia in Spain. Results are presented of a nation-wide inquiry into the management of hemophilia in Spain. It is calculated that there are 1,172 hemophilic patients in the country. A survey has been made of the therapeutic materials (prepared commercially or by hospitals) used in 1974 and their availability in the various hospitals of the Social Security Service. It is estimated that an average of 10,708 units of deficient factor were used per patient in this year. The number of patients on home therapy is 1.2% of the total. All cost of hemophilia treatment is covered by the Social Security. Comments are made on progress during the last five years.


Management of hemophilia in France.

Management of hemophilia in France. Two important factors concerning the management of hemophilia in France are considered. The supply of factors VIII and IX for replacement therapy meets the current demand but as the demand increases with the development of self-infusion programs, the production will also have to increase. This can only be done through more effective use of all of the blood components and will require careful evaluation of the needs of each patient. Programs which teach self-infusion and the other aspects of home care are gradually allowing the hemophiliac and his family better understanding of the disease. These programs are developing slowly in France but must be expanded to improve the general care of all French hemophiliacs.


Haemophilia in Australia.

Haemophilia in Australia. The major problems currently facing haemophilia management in Australia relate to (1) a need for better co-ordination of our entire national effort for haemophilia therapy and (2) a need to improve the efficiency of our preparation of factor VII concentrates. If we could simply double or treble our factor VIII yields from the same volume of donor plasma many of our urgent treatment problems could be solved.


Four heparin preparations: anti-Xa potentiating effect of heparin after subcutaneous injection. Four different heparin preparations--sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m.w. 9,000) and high molecular weight sodium heparin (mean m.w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i.u./ml) at 3-4 hours after the injection. With sodium heparin (m.w. 15,000) the highest values (0.135 i.u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0.072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 i. u./ml at 3-4 hours after injection). These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.


On the value of the activated partial thrombo-plastin time (aptt) in monitoring heparin therapy. Of 1068 blood samples referred for evaluation of the haemostatic mechanism 135 contained heparin as judged by the polybrene titration method. Of the 57 samples with a heparin concentration in the defined therapeutic range, 65 per cent had APTT values in the "therapeutic range". Of the samples from patients who had not received any anticoagulant, 213 (24 per cent) had prolonged APTT, and 48 of these samples had APTT values in the "therapeutic range" for heparin therapy. It is suggested that the APTT test is of limited value in monitoring heparin therapy.


Alteration of plasma antithrombin III levels in ischemic heart disease. The amount of antithrombin III in plasma was determined quantitatively in 218 males between 45-60 years of age. The mean antithrombin III value was found to be low in the group with low risk for ischemic heart disease, intermediate in the group with high risk for ischemic heart disease and highest in the group with acute myocardial infarction. Concomitant study of kaolin-activated partial thromboplastin time revealed a sharp decrease in its mean value in the group with acute myocardial infarction. The high correlation between antithrombin III and kaolin-activated partial thromboplastin time for the entire population suggests that the development of ischemic heart disease is a gradual process and that failure of the damping mechanism results as an acute event. These findings may be useful in the determination of the coagulation state of these patients.


The influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and factor X in the rat. The influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and X was studied in the rat. Disappearance rates of the three coagulation factors were measured after synthesis had been blocked with appropriate doses of warfarin, and reappearance rates were assessed upon induction of synthesis by high doses of vitamin K1 injected into rats displaying coumarin induced hypocoagulability. No statistically significant difference in the disappearance and production rates of any of the factors could be found between normal euthyroid rats and thyroxin-treated hypothyroid rats proven to be euthyroid. The differences between the two euthyroid groups and the hypothyroid group were highly significant, however: hypothyroidism results in an approximately 50% decrease of the metabolic rates of the three coagulation factors under study. The reappearance of the three factors, under euthyroid as well as hypothyroid conditions, showed a biphasic pattern: in the first two hours after vitamin K1 administration to warfarin treated rats, a rapid reappearance was observed, to the same extent for all three factors, in hypo- as well as euthyroid rats. This finding suggests that in vitamin K1 deficiency an intracellular accumulation of precursor proteins (PIVKAs) occurs, which after rapid conversion into biologically active coagulation factors by vitamin K1 are shed into circulation. The subsequent phase of reappearance is much slower and reflects the synthesis rate of coagulation enzymes. It is characteristic for each factor and clearly slower in hypothyroid rats than in euthyroid rats. From this an influence of thyroid function on the synthesis rate of the protein moiety of coagulation factors can be inferred. An apparent difference between disappearance and reappearance rate of the coagulation factors in the plasma, particularly pronounced for factors VII and X in euthyroid rats, could theoretically be explained as the consequence of the model used for derivation of these rates.


Fibrinogen/fibrin degradation products in serum of patients with idiopathic thrombocytopenic purpura: elevated levels during severe thrombocytopenic phase of the disease. Sera from 23 patients with idiopathic thrombocytopenic purpura (ITP), 14 patients with aplastic anemia with severe thrombocytopenia and healthy control subjects were tested for the presence of fibrinogen/fibrin degradation products (FDP), using the tanned red cell hemagglutination inhibition immunoaassay. The concentrations of circulating FDP of ITP patients (mean 12.01 mug/ml) were significantly higher than those of the patients with aplastic anemia (mean 4.01 mug/ml, p less than 0.05) or normal controls (mean 3.10 mug/ml, p less than 0.001). The patients with untreated ITP with very low platelet counts had higher levels of FDP than those of the treated group (p less than 0.01). Serum FDP and a battery of other coagulation-fibrinolysis tests were serially carried out over a period of 10 weeks in two patients with ITP. The initially high FDP promptly decreased as circulating platelets increased in response to steroid in both patients, while plasma fibrinogen, euglobulin lysis time, prothrombin time and partial thromboplastin time remained essentially normal during the course of observation. The exact source of the increased serum FDP in ITP was not established, but a few possible mechanisms responsible for this abnormality were discussed.


Effect of thrombin on phosphorylation of platelet membrane proteins. The effect of thrombin on the phosphorylating activity of platelet membranes was compared to that of trypsin. Preincubation of non-32P phosphorylated platelet membranes with or without either of these two enzymes resulted in a considerable loss of membrane protein kinase activity which was most severe when trypsin was used. Protein kinase activity and endogenous protein acceptors decreased in parallel. 32P-phosphorylated membranes showed a slow but progressive loss of label which was accelerated by trypsin. Thrombin under these conditions prevented the loss of 32P-phosphate. These results are interpreted to indicate a thrombin-induced destruction of a phosphoprotein phosphatase. The protein kinase activity of phosphorylated platelet membranes using endogenous or exogenous protein substrates showed a significant reduction compared to non-phosphorylated membranes suggesting a deactivation of protein kinase by phosphorylation of platelet membranes. Neither thrombin nor trypsin caused a qualitative change in the membrane polypeptides accepting 32P-phosphate but resulted in quantitative alterations of their ability to become phosphorylated.


The variability of platelet-collagen interaction. Its influence on aspirin-induced inhibition of platelet aggregation. A study of platelet aggregation induced by progressive concentrations of collagen was performed in 40 normal persons, equally grouped by sex, immediately before, and 90 min after, the ingestion of 0.500 g aspirin. Simultaneously, serum ASA-esterase activity and plasmatic salicylic acid levels were investigated in the pre- and post-ASA samples respectively. Wide individual variations in platelet responsiveness to collagen were found when the minimal amount of the aggregating agent necessary to provoke significant aggregation was located. The percentage of aggregation and the slope were the most sensible indicators of both the individual variances and the ASA-induced inhibition. Correlation was found in both groups between the minimal amounts of collagen required for initiating aggregation pre- and post-ASA. Also positive correlation was found between the minimal collagen concentration required to initiate aggregation pre-ASA and the aspirin-induced inhibition in the aggregation produced by a higher collagen concentration. Important individual and sexual differences were detected in the serum content of ASA-esterase activity. A negative significant correlation was demonstrated between the ASA-esterase activity and the differences in collagen concentrations necessary to start aggregation pre- and post-aspirin in the men group. Failure to consider individual variances in platelet reactivity may lead to false conclusions about the ASA affectiveness as an antithrombotic agent.


On the measurement of spontaneous platelet aggregation. The platelet aggregation test III. Methods and first clinical results. A new measuring device was developed for the study of "spontaneous" aggregating activity of thrombocytes. In the photometric platelet aggregation test (PAT III) 0.6 ml of platelet-rich plasma (PRP) are rotated in a disc-shaped cuvette at 20 rpm and 37 degrees C. Changes in optical density of PRP which are induced by the formation of platelet aggregates are continuously registered using a chart recorder. PAT III was developed for the detection of enhanced platelet aggregation, indicating a risk of thrombosis and thromboembolic complications. In 146 healthy individuals a certain percentage showed slight primary aggregation (alpha1) which in some cases was followed by marked aggregation (alpha2) at a certain time (Tr) after the beginning of rotation. The percentage of individuals showing alpha2 increased with age. An increase of plasma pH in the rotating sample, which was caused by diffusion of CO2, was an important conditioning factor for aggregation. The test results depended on the platelet count in PRP. Aggregation curves were suppressed by admixture of erythrocytes and lipid turbidity. The tendency of platelets to aggregate increased within 60-90 min following blood sampling. During this period the interval to the onset of aggregation (Tr) became shorter and the maximum aggregation speed (alpha 2) increased with time. PAT III yielded reproducible results when it was carried out more than 60 min after blood drawing. In a group of 327 diabetic patients "spontaneous" aggregation occurred more frequently in all age groups as compared with the controls. Additional equipment was available for the registration of ADP-, collagen-, or epinephrine-induced aggregation similar to Born's and O'Brien's method. The device can easily be mounted on an Eppendorf photometer without further alterations.


Fibrinogen response to turpentine and endotoxin in busulfan-treated rabbbits. The response of the plasma fibrinogen level to the subucutaneous injection of turpentine and to the intravenous injection of endotoxin was measured in normal rabbits and in rabbits made granulocytopenic and thrombocytopenic with busulfan. Plasma fibrinogen levels rose sharply in both normal and busulfan-treated rabbits and the extent of the rise in fibrinogen level after turpentine. As discussed herein, these data are consistent with the hypothesis that material from granulocytes plays a pathophysiologic role in the stimulation of fibrinogen synthesis in inflammation and after tissue trauma.


Spontaneous platelet aggregation in arterial insufficiency: mechanisms and implications. To investigate the clinical implications and mechanisms of spontaneous platelet aggregation (SPA) in man, 150 normal subjects, 22 patient controls and 130 patients with vascular insufficiency were studied. SPA was negative in normal subjects and patient controls whereas it was positive in 36 of 66 (54%) patients with transient ischemic attacks, 6 of 32 (19%) patients with stable angina, 7 of 10 (70%) patients with acute myocardial infarction and 11 of 14 (80%) patients with acute peripheral arterial insufficiency. The SPA was inhibited with aspirin in vivo, and inhibited competitively in vitro by low concentrations of aspirin, 2-chloroadenosine, prostaglandin E1 or apyrase but only by high concentrations of heparin or hirudin. Addition of platelet-poor plasma from patients with positive SPA did not cause normal platelets to aggregate. Treatment of patients who had acute peripheral arterial insufficiency with aspirin and dipyridamole prevented SPA with notable clinical improvement of the ischemic changes.


Oxygen consumption in platelets of newborn infants before and after stimulation by thrombin. The authors compared the oxygen consumption in platelets from the umbilical cord blood of 36 healthy newborn infants with that of 27 adult subjects, before and after thrombin addition (1.67 U/ml). Oxygen consumption at rest was 6 mumol/10(9)/min in adult control platelets and 5.26 in newborn infants. The burst in oxygen consumption after thrombin addition was 26.30 mumol/10(9)/min in adults and 24.90 in infants. Dinitrophenol did not inhibit the burst of O2 consumption in platelets in 8 out of 10 newborn infants, while the same concentration caused a decrease in 9 out of 10 adult subjects. Deoxyglucose inhibited the burst in O2 consumption in newborn infant and adult platelets by about 50%. KCN at the concentration of 10(-4) M completely inhibited basal oxygen consumption but did not completely inhibit the burst after thrombin. At the concentration of 10(-3) M, it inhibited both basal O2 consumption and the burst in infants and adult subjects.


Effects of dextran on the molecular structure and tensile behaviour of human fibrin. Characteristic changes induced by dextran during the conversion of fibrinogen to fibrin have previously been shown to be associated with profound alterations in morphology of fibrin. However, whether dextran is incorporated into the fibrin molecule and whether morphological changes are associated with alterations in mechanical behaviour of formed fibrin was unclear. The investigations described show that the fibrin made in the presence of dextran has a shortened syneresis time, a lowered modulus of elasticity, an increased elongation and diminished ultimate strength at break. The molecular composition of fibrin clots remains unaltered despite the altered mechanical properties and morphological changes. Furthermore, dextran is not incorporated into the fibrin structure in any appreciable quantity. It is suggested that these several effects of dextran on clot morphology, tensile behaviour and kinetics of fibrin formation arise from increased forces of attraction between fibrin molecules such that fibrin chains are held together by weak secondary cross-links rather than by stronger primary cross-links which are hidden within the thicker fibrin chain bundles.


[Effect of preparations of messenger RNA from the spleens of immunized rats on antibody synthesis in rat lymphosarcoma]. Messenger RNA was isolated from spleen polysomes of rats immunized with sheep red cells, two methods being employed: a sorption of mRNA on on membrane filters, and poly(U)-cellulose affinity chromatography. The rat transplantable lymphosarcoma cells treated with this RNA started hemolysine synthesis which persisted throughout many cell generations in transplantation of the tumor. The probability is discussed of m-RNA not only functioning as a template for antibody synthesis but also deblocating appropriate genes in recipient cells.


A new oxisuran metabolite.

A new oxisuran metabolite. 1. An unidentified oxisuran metabolite which had been observed in animal urine was biosynthesized by incubating [14C]oxisuran with rat liver cytosol. 2. The metabolite, isolated by preparative t.l.c. and extraction, was identified as oxisuran alcohol sulphide by mass fragmentography. Confirmation of this identification was obtained by biosynthesis of the same compound from oxisuran sulphide. 3. The 9000 g supernatant liquid from rat liver was less effective than cytosol in reducing oxisuran to its alcohol sulphide. Neither rat liver fraction reduced oxisuran alcohol sulphoxides to sulphide. 4. The 9000 g fraction oxidized oxisuran and oxisuran alcohol sulphoxide to oxisuran alcohol sulphone.


[Ileus due to appendicitis in the puerperium]. A report is given in a case of appendicitis after delivery in childbed. This was the third case of appendicitis within 17 657 deliveries in the gestation of the district hospital in Sangerhausen in the period from 1960 to 1975. The chronic relapsed appendicitis produced a paralytic Ileus. By using correspondent measures (infusional therapy, appendectomy, adhesion solutions) the patient could be cured without any complications. The patient feeled a Douglas-touch of pain that extended especially to the right. This was the only symptom that was noticed by the patient besides the Ileus that had been clinical well defined and secured with the help of x-ray photo.


Biologically active luteinizing hormone (LH) in plasma. 1. Validation of the in vitro bioassay when applied to plasma of women. A recently described in vitro bioassay method for the measurement of biologically active LH (Van Damme et al. 1974) has been applied to the plasma of normally menstruating and post-menopausal women. The specificity of the procedure was established according to the following evidence: 1. Parallelism was observed between dose response curves obtained with serial dilution of a standard LH preparation (HMG 2nd IRP) and plasma pools collected during the follicular phase, at the LH-peak, during the luteal phase and after menopause. 2. There was no evidence for the presence of any synergistic or antagonistic factor in the various plasma specimens. The assay design used to establish this consisted of assaying the standard and plasma pool separately and then together as a mixture followed by an assessment of the difference (if any) in the potencies obtained. Strict additivity should yield a relative potency of 1.0. Plasma pools which were obtained every 2-3 days throughout the menstrual cycle were assayed using this design against the standard (HMG 2nd IRP) and against a mid-cycle plasma pool obtained at the time of the LH-peak. The latter was also assayed against partially purified plasma fractions obtained from a post-menopausal plasma pool after gel filtration and isoelectric focusing. With the exception of 3 assays, in which the estimates of relative potency were 0.91, 0.94 and 0.95, respectively, in 19 assays of additivity, the fiducial limits always included unity. 3. Non-detectable LH levels were found in the plasma or serum of either hypophysectomized or hypopituitary hypogonadal men or women treated with oestrogen/progestogen combined pills. 4. The presence of calf of human serum in the assay medium is an essential requirement for a valid comparison of standard and unknown preparations. In their absence, non-parallel dose response curves between plasma and stardard were obtained. The other established criteria of reliability (sensitivity and precision) were also examined. The method is sufficiently sensitive (3.5-8.0 mIU/ml plasma; HMG (2ng IRP) as standard) for the measurement of LH throughout the cycle. The mean index of precision (gamma) in 230 multiple assays was 0.040. It is concluded that the modified bioassay yields valid and reliable estimates of LH when applied to human plasma obtained throughout the menstrual cycle and after menopause.


The primary empty sella an endocrine study on 12 cases. Twelve patients (10 women and 2 men) with a primary empty sella turcica were studied. Endocrine function tests were performed as follows: growth hormone (GH) was measured after insulin-induced-hypoglycaemia, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after LH-releasing hormone, thyrotrophin (TSH) and prolactin after thyrotrophin-releasing hormone; pituitary reserve of adrenocorticotrophin (ACTH) was determined by measurement of plasma cortisol after lysine-vasopressin and 11 deoxycortisol after metyrapone. Five of the patients (group A) had no endocrine disturbance. Seven patients (group B) had a hypothalamo-pituitary disorder. Two of them had panhypopituitarism which appeared in one case after meningoencephalitis and in the other after a severe cranial trauma. In two cases an amenorrhoea-galactorrhoea syndrome with increased prolactin level (68 and 230 ng/ml) led to a diagnosis of a prolactin producing adenoma, which was confirmed by surgery. Finally three cases of amenorrhoeagalactorrhoea, with normal prolactin level, and/or diabetes insipidus remained unexplained. However, no causal relationship could be demonstrated between the pituitary disturbance and the "empty sella". Primary empty sella turcica is therefore a neuroanatomical and neuroradiological entity with no endocrine implication. A pituitary disorder might suggest a microadenoma or an incidentally associated disease.


Pregnant mare's serum gonadotrophin. I. Progesterone or prolactin and the reversal of antifertility efficacy of pregnant mare's serum gonadotrophin. A single consistent luteolytic dose of 10 IU PMSG given on day 5 of pregnancy caused complete resorption of foetuses and placentae associated with a polyfollicular ovarian state in rats. Concomitant treatment with progesterone or prolactin given concurrently with PMSG was found to overcome the antifertility efficacy of PMSG and maintained the endocrine balance favouring pregnancy maintenance. It was postulated that the PMSG-induced ovarian polyfolliculogenesis might be responsible for luteolysis of the corpus luteum gravidarum.


Analysis of suckling-induced changes in adenohypophyseal prolactin concentration in the lactating rat by three assay methods. Suckling-induced changes in adenohypophyseal prolactin (PRL) concentrations in lactating rats were measured in two experiments by three assays: a disc electrophoretic assay (DEA), a bioassay (BA) and a radioimmunoassay (RIA). Substantial discrepancies among the three assays were found in the absolute amounts of pituitary PRL measured and in the changes in adenohypophyseal PRL concentration that were recorded between suckling intervals. The results indicate that in dynamic states of secretory activity the correspondence among BA, RIA and DEA estimates of pituitary PRL concentration is poor.


Effect of cold-exposure on serum thyrotrophin levels in man. Serum TSH levels were measured after exposing male volunteers to cold, or successively to warmth and to cold, causing clear changes in body temperature. Very moderately heated Finnish sauna bath increased body temperature to about an average of 39 degrees C, and cooling in a relatively warm swimming pool (+25 to +28 degrees C, 30 min) decreased body temperature to below 35 degrees C after sauna, and to about 33 degrees C without sauna. In both cases a slight but significant initial increase of serum TSH was demonstrated. No changes in serum T3 or ETR were seen. The results suggest that a similar mechanism of initial TSH response may exist in humans as has previously been demonstrated in rats.


An inter-laboratory comparison of total serum triiodothyronine determination. L-triiodothyronine (T3) standards and an unknown serum were prepared and distributed to 18 different laboratories. T3 was determined on the standards and both T3 and T4 were assayed on the serum. The T3 and T4 results varied widely with a mean variance of 36 and 23%, respectively. There was, however, a positive correlation between the T3 values obtained within each laboratory and results of the unknown serum. Thus, while the data of each laboratory is internally consistent, the data between laboratories cannot be compared without an appropriate reference sera. From this fact, it is concluded that absolute ("true") T3 concentrations in human serum is not yet known. Because of the small number of laboratories involved in this comparison, it was not possible to determine which factors of the various procedures are responsible for the variance of the T3 results.


Hormonal and biochemical changes in patients successfully operated for primary hyperparathyroidism. Six patients with primary hyperparathyroidism were studied during the first seven days after the operative removal of the parathyroid adenoma with special emphasis on biochemical and hormonal changes during the first 24 h. Serum parathyroid hormone (PTH) levels fell abruptly after the parathyroidectomy and normalized within 3 h. The half-life of the biologically inert c-terminal PTH-fragment (M.W. 7000-7500) was calculated to be about 180 min. No significant changes in serum calcitonin levels were found. The serum phosphorus levels, which were already low pre-operatively, decreased transiently but significantly during the first 90 min after the removal of the parathyroid adenoma. This fall in serum phosphorus preceded a slow decrease of the calcaemia. During the first post-operative week the calcaemia continued to decline, while serum phosphorus levels increased. The pre-operative cholesterol levels were low compared to age-paired normal Belgians. During the first post-operative week the cholesterolaemia decreased even more, whereas at long term follow-up a clearcut increase of the serum cholesterol levels has to be expected.


Metabolism of progesterone in uterine tissue of non-pregnant rats in vitro. The metabolism of labelled progesterone was studied in vitro in uterine tissue of non-pregnant rats with particular emphasis on the influence of substrate concentration. Neither a qualitative nor quantitative difference was found for a steroid tissue ratio between 15 X 10(-6) and 4.2 X 10(-9) to 1 g (substrate amounts between 57.73 and 0.02 nmol); with both concentrations 42 to 44 per cent of progesterone was metabolized to about 35 per cent monohydroxymonoketonic steroids and 4-6 per cent dihydroxylated C21O2-compounds. In both sets of incubations we have isolated and identified the following steroids: 3alpha-hydroxy-5alpha-pregnan-20-one, 3beta-hydroxy-4-pregnen-20-one, 3alpha-hydroxy-4-pregnen-20-one, 20alpha-hydroxy-4-pregnen-3-one, 5alpha-pregnane-3alpha,20alpha-diol and 4-pregnene-3alpha,20alpha-diol. The most abundant metabolite formed in these incubations was 3alpha-hydroxy-4-pregnen-20-one which corresponds to about 30 per cent of the total activity recovered. It is the first time that the presence of 20alpha-hydroxysteroid-oxidoreductase activity is definitely established in this type of tissue. The identification of three allylic alcohols as progesterone metabolites in the rat uterus confirms that delta4-3-hydroxysteroids are important intermediates in the in vitro uterine metabolism of steroids.


Metabolism of 20beta-hydroxy-4-pregnen-3-one in uterine tissue of non-pregnant rats in vitro. In vitro experiments carried out with uterus preparations of ovariectomized adult rats indicate the presence in this tissue of a 20beta-hydroxy-steroid-oxidoreductase which catalyzes the conversion of 20beta-hydroxy-4-pregnen-3-one to progesterone. Since a hepatic 20beta-hydroxysteroid-oxidoreductase is absent in adult female rats, the myometrial enzyme can be responsible for the biological activity of 20beta-hydroxy-4-pregnen-3-one in these animals. Besides progesterone five metabolites were isolated and identified after incubation of [4-14C]20beta-hydroxy-4-pregnen-3-one with uterine tissue: 20beta-hydroxy-5alpha-pregnan-3-one, 20beta-hydroxy-5beta-pregnan-3-one, 5alpha-pregnane-3alpha,20beta-diol, 4-pregnene-3alpha,20beta-diol and 4-pregnene-3beta,20beta-diol. The conversion of 20beta-hydroxy-4-pregnen-3-one to progesterone permits us to regard all five steroids isolated as progesterone metabolites in the rat uterus. 20beta-hydroxy-5beta-pregnan-3-one is the first C21-metabolite with a 5beta(H)-configuration isolated in the rat uterus, which indicates the presence of 5beta-reductase in this tissue.


Mammotrophic activity in rat serum during the oestrous cycle, pregnancy and lactation. The mammotrophic activity of various serum samples was assessed on the mammary gland of pregnant rats, in organ culture. Insulin was added to the medium. Serum samples from virgin rats showed little activity, and variation in mammotrophic activity during the oestrous cycle was slight. During pregnancy a significant increase in proliferative activity was not seen during the first week, but around day 8-9 mammotrophic activity increased sharply. The activity showed maxima around days 12 and 19. A decrease in the activity between these maxima was not consistently observed. Mammotrophic activity was still present in sera collected during parturition, and 30 min after parturition. It had disappeared completely within 24 h. The mammotrophic factor detectable by organ culture in the serum of pregnant rats could be rat chorionic mammotrophin. Activity in the serum on day 0 and 1 of lactation was comparable to that of virgin rats, but some activity appeared on day 2. High actvities were foound frequently around day 4 to 6 of lactation. On other days the activity showed fluctuations without a definite pattern. Litter size was of minor importance but the combination of a larger litter size and fasting-overnight seemed to suppress the presence of mammotrophic activity in the serum. Nursing was important: after weaning the activity has disappeared, while renewed nursing after weaning resulted in the appearance of high levels of activity. The mitotic activity obtained with lactating rat serum in the culture was suppressed by addition of rabbit anti-rat prolactin serum to the medium. This suggests that the main mammotrophic factor detectable by organ culture in the serum of lactating rats, is prolactin.


Influence of the foetus, placenta and ovary on the mammotrophic activity of pregnant rat serum. Serum mammotrophic activity was assayed using an organ culture technique with histological endpoints. Using sera of 13 days pregnant rats with 1 to 18 conceptuses, activity was detectable even in the presence of 1 conceptus, but the activity with 1-4 conceptus(es) tended to be less than with 6-18. Serum of rats with 1-3 conceptus(es) was approximately 2-4 times less active than serum of rats with 14 conceptuses. Removal of the conceptuses on day 15 caused loss of mammotrophic activity of the serum, tested 4 days later. When the foetuses, the ovaries or both the foetuses and ovaries were removed on day 15 of pregnancy, mammotrophic activity was present in the serum collected 4 days later. Differences in activity between the treated groups were small. The mammotrophic activity was comparable to the activity of serum of untreated 15 days pregnant rats or 19 days sham-operated pregnant rats. Explanted single fragments of a 19 days pregnant rat placenta released activity into the medium. The placenta retained this capicity even when the foetus had been removed 4 days previously.


Testosterone and 5alpha-androstan-17beta-ol-3-one (DHT) levels in man. In order to test the hypothesis that plasma 17beta-hydroxy-5alpha-androstan-3-one (DHT) levels might represent a parameter of androgenicity independent of testosterone (T) levels, the T/DHT ratio was determined at low and high T levels in both sexes. High T levels in males were obtained either by stimulation of endogenous T secretion, but im injection of either short or long-acting T esters and finally by oral administration of 200 mg of crystalline testosterone. In females high T levels were obtained either by im injection of long-acting T esters or by oral administration of 200 mg of T. It was observed that the T/DHT ratio was not a function of sex but a function of T levels, whether T had an endogenous or a exogenous origin. When, as in patients with porto-caval shunt or cirrhosis of the liver, the liver was bypassed, oral administration of T resulted in relatively higher DHT levels than expected from T levels: this suggests an extra-hepatic origin of plasma DHT and/or a decreased hepatic metabolism of DHT. In a patient with the testicular feminization syndrome the T/dht ratios both under basal conditions and after im injection of T propionate were similar to those observed in normal subjects.