VH subgroup restriction in human erythrocyte antibodies: studies of anti-A, anti-B, and anti-Duffy antibodies. IgG from 13 anti-A, 26 anti-B, and 10 anti-Duffy antisera were used to coat human erythrocytes. With antisera specific for each of the three VH subgroups, VHI, VHII, and VHIII, a clear VH subgroup restriction was shown in these antibody preparations. Of the 26 IgG anti-Bcoated cell preparations, 21 were agglutinated exclusively by the anti-VHIII antiserum, and 5 were agglutinated mainly by the anti-VHIII antiserum but showed also some reactions using anti-VHI or anti-VHII antiserum, or both. Similarly, 11 out of the 13 IgG anti-A antibodies belonged to VHI, and only 2 to VHIII. The 6 Igg anti-Fy(a)antibodies were restricted to subgroups VHI and VHII, and of the 4 IgG anti-Fy(b) antibodies, 3 belonged to subgroup VHIII and one to VHII. Additional experiments indicated that IgM anti-A and IgM anti-B antibodies showed the same type of restriction to VH subgroups as the corresponding IgG antibody preparations.


VH subgroup restriction in human erythrocyte antibodies: Studies of anti-A, anti-B, and anti-Duffy antibodies. IgG from 13 anti-A, 26 anti-B, and 10 anti-Duffy antisera were used to coat human erythrocytes. With antisera specific for each of the three VH subgroups, VHI, VHII, and VHIII, a clear VH subgroup restriction was shown in these antibody preparations. Of the 26 IgG anti-B-coated cell preparations, 21 were agglutinated exclusively by the anti-VHIII antiserum, and 5 were agglutinated mainly by the anti-VHIII antiserum but showed also some reactions using anti-VHI or anti-VHII antiserum, or both. Similarly, 11 out of the 13 IgG anti-A antibodies belonged to VHI, and only 2 to VHIII. The 6 IgG anti-Fy(a) antibodies were restricted to subgroups VHI and VHII, and of the 4 IgG anti-Fy(b) antibodies, 3 belonged to subgroup VHIII and one to VHII. Additional experiments indicated that IgM anti-A and IgM anti-B antibodies showed the same type of restriction to VH subgroups as the corresponding IgG antibody preparations.


Ligand-induced redistribution and augmentation of surface-bound myeloma protein on MOPC 315 plasmacytoma cells. The dinitrophenyl (DNP)- and trinitrophenyl (TNP)-binding IgA(lambda2) myeloma protein M315, bound on the surface of MOPC315 mouse plasmacytoma cells, was redistributed into spots, patches, and, more rarely, into caps by TNP14-BSA and by divalent but not monovalent anti-M315 antibodies. Antiserum to the L-chain of M315 (L315) induced similar redistribution of L315 bound on the surface of variant cells that only produced L315. The spots were much larger and more brilliant when the cells were incubated with the ligands at 37 degrees C than at 4 degrees C. Redistribution of M315 also occurred on M315-producing cells in peritoneal diffusion chambers incubated in BALB/c mice producing antibodies against the M315 idiotype. The clearance of immune aggregates and the regeneration of new surface-bound M315 in diffusion chambers were much slower for MOPC315 cells than that reported for B lymphocytes. The total pool of M315 was 1.9 pg per cell (about 8 x 10(6) 7S molecules), but only an average of 6 x 10(3) [125I]TNP-BSA molecules were bound on the surface of each MOPC cell at 4 degrees C. The amount of surface-bound TNP-BSA increased eightfold when the cells were preincubated at 37 degrees C with rabbit anti-mouse IgA; at 4 degrees C the increase was only twofold. The data indicate that multivalent ligands specific for M315 induce an accumulation of M315 on the cell surface that correlates with secretion; the immediate precursors of secreted myeloma protein may be arrested in their transit through the membrane by the ligands.


The effect of various metal ions and chelating agents on the formation of noncovalently and covalently linked IgM polymers. The influence of various concentrations of Mg2+, Ca2+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+, EDTA, or 8-hydroxyquinoline-5-sulfonic acid on the formation in vitro of polymeric IgM from reduced and dissociated IgM has been investigated. 4-200muM Zn, Cd, or Hg ions in the dialysis buffer used for reassociation resulted in the formation of a homogeneous polymer peak sedimenting as 19S IgM, whereas the other metal ions resulted in the formation of polymers sedimenting mostly as tetramers, pentamers (19S IgM), and hexamers. Dialysis in the presence of 1 and 3mM EDTA or 8-hydroxyquinoline-5-sulfonic acid gave slight polymer formation; 10 mM of the agents gave none. Ca, Mg, Fe, Ni, Zn, Cd, or Hg ions regularly gave only noncovalently linked polymers, whereas Cu ions in particular, but also Co and, to a minor extent, Mn ions catalyzed the formation of covalently linked polymers. Experiments performed with Mg, Ca, Ni, and Zn ions or with Cu and Zn ions in the same buffer during reassociation showed that Zn ions inhibit the effect of the other ions on polymer assembly and covalent stabilization.


A new specific quantitation-in-gel method differentiating commercial human serum standards intended for RID analyses. A rapid, sensitive technique is described which measures small amounts of protein applied on agarose gel containing specific antibody. Alternating current through the gel reduces the influence of diffusion, and specific immunoprecipitate spots are formed. Their density after staining is proportional to applied protein. Quantitation of IgG and IgA in human serum standards was highly reproducible (P less than 0.001, Spearman coefficient of rank correlation test), and as little as about 35 ng Ig could be detected. Results are available within hours. Human sera and some purified preparations of 7S IgG and secretory IgA were grouped according to immuno-gel filtration findings. The group of samples containing fragments, aggregates, or unusually small amounts of monomeric IgG or IgA was also differentiated by specific immunoprecipitate spot (SIS) analysis from those mainly monomeric in character (Wilcoxon rank test, P less than 0.02). A World Health Organization reference serum (67/97) was used as standard. The study indicates that a human serum pool stored in aliquots at -20 degrees C is a good standard for quantitating serum IgG and IgA and that purified preparations are no better. It is suggested that the SIS assay could be advantageously applied to screening biologic fluids for unusual amounts or types of IgG and IgA.


Alkaline phosphatase in the developing bursa of Fabricius. A comparative study of the cyclophosphamide- and testosterone-induced immunodeficiencies in the chick embryo. The ontogeny of alkaline phosphatase in the bursa of Fabricius was studied by histochemical and biochemical methods. According to the quantitative determinations, the activity of alkaline phosphatase increased from the 11th to 17th day of incubation--that is, during the time of the lymphoid follicle formation in the developing bursa. The activity was localized in the mesenchymal tissue surrounding the lymphoid follicles. Testosterone given in ovo prevented the appearance of alkaline phosphatase in the bursal mesenchyme but had no effect on the activity of the embryonic liver. In contrast, in ovo treatment with cyclophosphamide had no effect on the alkaline phosphatase in the bursa. By using transplantation of embryonic bursal stem cells, it was further shown that, in contrast to cyclophosphamide, testosterone destroys the capacity of the bursa to serve as a differentiation site for the B-cell lineage. The results indicate that testosterone affects the stromal cells of the bursa, whereas cyclophosphamide destroys only the lymphoid population undergoing differentiation and leaves the bursal stroma intact.


Urinary excretion of ten plasma proteins in patients with renal carcinoma. Urinary and serum proteins were studied preoperatively in 48 patients with renal carcinoma, using an automated immunoprecipitin reaction. The 24 h excretion and the renal clearance of albumin, transferrin, haptoglobin, IgG, IgA, and IgM and the 24 h excretion of the immunoglobulin lambda and kappa free light chains and beta2-microglobulin were significantly increased compared with a control group. The excretion of lysozyme was also increased, but not significantly. Increased protein excretion was the most common urinary finding in patients with renal carcinoma. The protein excretion was predominantly of the glomerular type, implying a glomerular injury. The serum concentrations of albumin and transferrin were significantly decreased and the serum concentration of haptoglobin significantly increased in patients with stage III and IV tumours compared with patients with stage I and II tumours. Abnormal serum concentrations of albumin, transferrin, and haptoglobin were indicative for advanced renal carcinoma.


[Loss of insulin during the infusion of insulin in glucose and nutrient solutions]. Controversial results of previous investigations prompted us to reassess the adsorptive loss of insulin to infusion bottles and tubings. An experimental array was chosen which was in strict accordance with the infusion technique used for the high-caloric parenteral nutrition of severely ill patients. The insulin concentrations were determined by a radioimmunoassay method. As in pure glucose solutions of various concentrations a loss of insulin amounting to about 30% was determined in high-caloric solutions containing aminoacids. The protective effect of human serum albumin, gelatine (Physiogel), and Rheomakrodex, all three of which diminish the insulin loss by about 50%, could be confirmed. The varying results obtained by different investigators may be attributable mainly to technical factors such as different surface properties of the infusion material, differences of the experimental array and analytical methods. Accordingly, variable losses of insulin may also occur in clinical practice. For daily routine an exact knowledge of these losses is irrelevant, since the insulin dosage is adjusted to the blood sugar level. However, if the insulin requirement is used as an index of the metabolic condition of the patient, precise determination of the actual loss is mandatory.


[Diphtheria epidemic in eastern Switzerland in 1974]. A diphtheria epidemic in the eastern part of Switzerland in 1974 and the measures which were taken for its management and eradication are described. In particular it is pointed out that at present diphtheria displays atypical clinical symptoms in Europe, a fact that renders the diagnosis very difficult in many cases. Therefore, it is important to perform a throat swab in every patient with suspected diphtheria; it is also necessary to explicitly require a search for C. diphtheriae. The early recognition and early treatment of diphtheria with penicillin or erythromycin is of the utmost importance in order to avoid neurological and cardiac complications. With regard to the management and eradication of a diphtheria epidemic, the most important measures are rapid antibiotic protection of all contacts and a widespread immunization of the population. Vaccination of adults with a DiTe vaccine containing a reduced amount of Di-toxoid is recommanded.


[The ossification of the ear cartilage in Addison's disease]. Stiffening and tenderness of the helix of the ear, with radiologically demonstrable calcific deposits, has been reported in various conditions such as frostbite, and also in Addison's disease. To a total of 14 clinical observations with only 4 well documented cases, a first autopsy report of the disorder in a case of tuberculosus Addison's disease is added. It is shown that the elastic cartilage of the pinna, of the epiglottis and of the trachea undergoes ossification without preceding dystrophic or metastatic calcification. The ossification has been observed only in males with longstanding Addison's disease treated exclusively with mineralocorticoids over a long period. The possible pathogenetic mechanisms are discussed. An important factor seems to be the long-standing glucocorticoid deficiency.


Cloned ribosomal RNA genes from chloroplasts of Euglena gracilis. Fragments of Euglena chloroplast DNA generated by endonuclease R-Eco RI were separated by agarose-gel electrophoresis into 24 distinct bands. At least five fragments contain sequences complementary to chloroplast ribosomal RNA, Most of the Eco RI fragments have been cloned in a plasmid of Escherichia coli. Three of the cloned fragments were shown to contain chloroplast ribosomal RNA sequences by DNA-RNA hybridization.


Interbacterial transfer of Escherichia coli--Drosophila melanogaster Recombinant plasmids. Recombinants were constructed between various Escherichia coli plasmids and fragments of Drosophila melanogaster DNA. These recombinant plasmids are nonconjugative, but can be mobilized from one cell to another by conjugative sex factors. Of 47 recombinants studied, 46 were mobilized at approximately the same or slightly lower frequencies than the parental plasmids, whereas one was mobilized 1000 times less efficiently.


In vitro growth of imaginal disks from Drosophila melanogaster. Imaginal disks were cultured in a new medium in vitrol Optimal growth occurred when the medium was supplemented with insulin and a juvenile hormone analog and conditioned by larval fat body. The disks grow in vitro by normal cell division and maintain their capacity to differentiate into normal patterns of adult cuticular structures.


Chromatic organization of primate cones. The distribution of baboon retinal cones were mapped histochemically by light-stimulated reduction of nitroblue tetrazolium chloride. Blue cones were distributed regularly in the periphery: red and green cones were distributed randomly everywhere. The ordering of cone densities was green > red > blue.


Antileukemia activity in the Osillatoriaceae: isolation of Debromoaplysiatoxin from Lyngbya. Chloroform extracts of several seaweeds, of the family Oscillatoriaceae, from Enewetak Atoll, Marshall Islands, display activity against P-388 lymphocytic mouse leukemia. A P-388 active compound, debromoaplysiatoxin, has been isolated from Lyngbya gracilis and characterized. This compound also has dermonecrotic activity and may be the dermatitis-producing substance in L. majuscula, the causative agent of "swimmers' itch" outbreaks in Hawaiian waters.


Hydrogen peroxide induces spawning in mollusks, with activation of prostaglandin endoperoxide synthetase. Addition of hydrogen peroxide to seawater causes synchronous spawning in gravid male and female abalones, and certain other mollusks as well. This effect is blocked by exposure of the animals to aspirin, an inhibitor of the enzyme catalyzing oxidative synthesis of prostaglandin endoperoxide. Hydrogen peroxide activates this enzymatic reaction in cell-free extracts prepared from abalone eggs (a very rich source of the prostaglandin endoperoxide synthetase); this effect appears to reveal a fundamental property of prostaglandin endoperoxide synthesis. Applicability of these findings to both mariculture and medical purposes is suggested.


Scotopic vision deficits in young monkeys exposed to lead. Rhesus monkeys were reared on diets designed to produce blood lead concentrations of 14 (untreated), 55, or 85 micrograms per 100 milliliters for the first year of life. Eighteen months later, blood lead levels were normal in all animals. At this time, however, visual discrimination performance in the 85-microgram group was impaired under dim light relative both to their own performance under bright light and to the performance of the other groups under all light levels used. We interpret these results to reflect a deleterious, enduring impairment of scotopic visual function (night blindness) as a result of early lead intoxication.


Evaluation of a serologic test for gonorrhea in a low-risk female population. This is a report of an evaluation of a new serologic test for gonorrhea--the Gonosticon Dri-Dot Test--as compared to the standard Thayer-Martin culturing technics in a low-risk female population. The Gonosticon Dri-Dot Test detected only 50% of the gonorrhea cases discovered by the conventional culture method. Furthermore, the serologic technic accounted for 17% false-positives, indicating that a reactive Gonosticon test is not necessarily consistent with active gonococcal infection. The efficacy of the Thayer-Martin culture plate diagnostic procedure for uncomplicated gonorrhea in women was reaffirmed by this study.


The psychiatrist's management of patients with undiagnosed brain neoplasm. Of 679 patients with brain neoplasms admitted to either a medical school center or a community hospital during a nine-year period, 24 had been examined by a psychiatrist before definitive diagnosis of brain neoplasm. These 24 cases were studied to evaluate the role of the psychiatrist in the management of the patients before the neoplasm was diagnosed. Such cases pose many subtle problems for psychiatrists. However, ten of the 24 patients either were sent for definitive tests by the psychiatrist with the tentative diagnosis of brain neoplasm or were triaged to other consultants to pursue that diagnosis.


Gamma heavy chain disease--presenting as pancytopenia and splenomegaly. A patient with gamma heavy chain disease (Franklin's disease) was discovered during evaluation for pancytopenia and splenomegaly. Lymphadenopathy, palatal edema, and infiltration of the bone marrow palatal edema, and infiltration of the bone marrow with abnormal cells were all absent. Serum and urine protein electrophoresis demonstrated a monoclonal protein migrating in the beta region. Immunoelectrophoresis showed that it reacted with antibodies against the Fc fragment of IgG heavy chains (gamma chains) but not with antibodies against kappa and lambda but not with antibodies against kappa and lambda light chains of Fab fragments. In the first year after detection of the disease, the patient had acute cholecystitis and disseminated herpes zoster. Sixteen months after diagnosis he died of overwhelming pneumonia caused by Pseudomonas aeruginosa and lebsiella neumoniae. A striking feature of his illness was his asymptomatic presentation, with pancytophenia and splenomegaly the only indication of this disease.


Malignant lymphoma of thenasopharyns in waldenström's macroglobulinemia: report of a case with severe epistaxis. An elderly woman with Waldenström's macroglobulinemia of four years' duration developed repeated severe epistaxis. This led to the discovery of a large malignant lymphoma of the nasopharynx. The clinical features of this rare case are discussed in relation to our present understanding of WM. Epistaxis in macroglobulinemic  patients may be associated with anatomic lesions of the nasopharynx.


The need to repeat lumbar puncture.

The need to repeat lumbar puncture. Four patients with bacterial meningitis are reported. On initial examination 1 patient had a slightly abnormal cerebrospinal fluid (CSF), and in the other 3 patients the CSF was completely normal. An obviously purulent CSF was obtained when lumbar puncture was repeated 14-48 hours later. All 4 patients presented initially with pyrexia, and either neck stiffness or convulsions. In 3 of the 4 patients a cause for pyrexia was found on initial examination but lumbar punctures were done for neck stiffness or convulsions to exclude meningitis. The problems and the need to repeat a lumbar puncture, as well as the importance of blood cultures in a patient with suspected meningitis, are discussed. The fact that a normal specimen of CSF does not exclude meningitis is stressed.


Antenatal diagnosis of Hurler's syndrome. Hurler's syndrome was diagnosed antenatally in the two consecutive pregnancies of a mother with one affected child. In both instances, diagnosis was based upon a demonstration of the presence of unusual glycosaminoglycan components in the amniotic fluid, of abnormal metabolic activity in cultured amniotic fluid cells, and a deficiency of the lysosomal enzyme alpha-L-iduronidase in these cell homogenates. Bothe pregnancies were terminated before the 24th week and the diagnosis was confirmed by biochemical studies of the fetal livers.


Sputum induction by saline aerosol.

Sputum induction by saline aerosol. A simple technique for inducing sputum production with vaporized 15% aqueous NaCl is described. Fifteen inhalations of saline aerosol, followed by a waiting period of 15-30 minutes, were sufficient to induce a productive cough in 93% of the persons tested. The apparatus is portable, cheap, easily maintained and suitable for use under field or hospital conditions.


Social welfare expenditures, fiscal year 1976. In 1976, for the second fiscal year in a row, public expenditures for social welfare purposes expanded at an abnormally high rate. Even after adjusting the 16-percent increase in aggregate expenditures for price and population changes, the 8-percent real growth rate proves to be the highest since 1971. The $45 billion rise in social welfare expenditures to a total of $331 billion reflects the effects of both recession and inflation. Benefits for the needy and the unemployed continued to expand at the same time that higher prices triggered cost-of-living adjustments in cash benefit programs and helped swell the cost of furnishing other social welfare services. A further reflection of this growth is the rise in the proportion of the Nation's gross national product devoted to social welfare expenditures from 19.7 percent in 1975 to 20.6 percent in 1976. The latter proportion becomes 27.5 percent when private social welfare spending is included.


National health expenditures, fiscal year 1976. The Nation's spending for health in fiscal year 1976 reached $139.3 billion, or $638 per person, according to preliminary figures. This total was 14 percent higher than the $122.2 billion spent for health in 1975. In the 2 years since price controls on the health industry were lifted, expenditures have risen $33.0 billion (31 percent). During this period, the economy has grown at a relatively slow pace with the gross national product increasing 18 percent. Thus, the percentage of the GNP attributed to health care reached 8.6 percent in 1976. Public and private spending rose 16 percent and 13 percent, respectively, in 1976, with the rise in public expenditures appreciably below the 22-percent increase of 1975. Third-party financing affected slightly more than two-thirds of all personal health care--the private insurance share at 26 percent and that of government 40 percent.


Conservative treatment of gastrointestinal fistulas. Conservative measures were instituted as the primary treatment of 39 consecutive patients with high output fistulas of the gastrointestinal tract and related organs. Nutritional status was maintained by an intravenous feeding regimen, using peripheral vein infusion sites and supplying 60% of the calorie intake by a fat emulsion. This regimen had no serious complications. These patients died during treatment. The fistulas healed spontaneously in 35 of the remaining 36 patients. None of these patients had obstruction distally or other factors tending to prevent spontaneous closure. Under these circumstances, nonoperative treatment is safest and best. Surgical closure was necessary in one patient after two months of conservative treatment and was successful.


Essential fatty acid deficiency associated with total parenteral nutrition. Essential fatty acid deficiency is a clinical and biochemical entity encountered in both adults and children. Especially at risk are those patients maintained by fat-free total parenteral nutrition. Linoleic acid is the substance most responsible for the deficien state and essential to its correction. A ratio of trienoic-tetraenoic fatty acids of 0.4 or greater is diagnositc of a chemical deficiency. A severe deficiency affects polyunsatured fatty acids, in both plasma and tissues and, thus, many systems of the body. Mulitple blood transfusions have not proved sufficient to correct chemical deficiency. A recently marketed, commercially available fat supplement, however, may be useful in preventing the problem.


Biliary lipid metabolism in the pregnant baboon. The serum cholesterol value, bile acid pool size and kinetics as well as lipid composition of gallbladder bile have been studied in seven baboons during nine pregnancies. During pregnancy, the per cent decrease in the average serum cholesterol value ranged from 25.6 to 74.4 per cent, mean 54.5 +/- 14.3 per cent, compared with that of antepartum averages. In seven of the nine pregnancies, chenodeoxycholic acid pool size decreased in the range of 40.1 to 86.6 per cent. In two pregnancies, the pool size of this bile acid was essentially unchanged. Total bile acid pool size also decreased from a mean of 990 +/- 260 milligrams antepartum to 520 +/- 200 milligrams in the third trimester, p less than 0.01. With regard to the cholesterol, phospholipid and bile salt content of gallbladder bile, cholesterol value decreased from an antepartum mean of 19.1 +/- 3.9 to 14.1 +/- 4.5 micromoles per milliliter in the third trimester. As a consequence, the lithogenic index of gallbladder bile decreased during pregnancy. The changes in chenodeoxycholic and total bile acid pool size are qualitatively similar to those reported by other investigators following the administration of estrogens to both baboons and other animal species. In the pregnant baboon, the decrease in pool size and in synthesis rate of bile acids is accompanied by a decrease in the cholesterol content of gallbladder bile. These changes in the lipid content of gallbladder bile are reflected in a decrease in the mean lithogenic index. These data suggest that the baboon may be an inappropriate model for studies of the relationship of pregnancy to cholesterol cholelithiasis in humans. In the baboon, both serum and biliary cholesterol values decrease during pregnancy. In humans, serum cholesterol levels increase during pregnancy. If the content of biliary cholesterol is a reflection of the serum concentration of this lipid, as has been suggested in recent studies, human bile may be more lithogenic during pregnancy. Additional studies are necessary to define the role of gallbladder contractility and bile stasis to gallstone formation during pregnancy.


Renal failure and the surgeon.

Renal failure and the surgeon. Surgical procedures can be accomplished successfully in patients with uremia provided certain principles of perioperative management are observed. Preoperative dialysis minimizes the biochemical derangements and improves fluid balance, hypertension and hemostasis. Drug schedules are adjusted in consideration of abnormal metabolism in renal disease. Anesthetic management is modified in recognition of potentially adverse or altered activity of anesthetic agents and neuromuscular relaxants. The lightest plane of anesthesia consistent with expeditious operative technique is maintained, since adequate tissue oxygenation is dependent upon increased cardiac output in these invariably anemic patients. Intraoperative hyperventilation sustains the usual compensatory mechanism for uremic metabolic acidosis in the conscious patient, thereby averting increments in serum potassium levels associated with increasing acidosis. Postoperative morbidity may include shunt thrombosis, infection, impaired wound healing, bleeding, pericarditis, pleuritis and pancreatitis. Hypervolemia and hyperkalemia are best managed by early postoperative dialysis. A period of nutritional support using intravenous essential L-amino acids and hypertonic glucose appears promising, especially when gastrointestinal dysfunction exists.


Ossifying fibroma of the occipital bone. A rare ossifying fibroma in the occipital bone is described, and the available literature reviewed. The rapid growth seen in this case was remarkable and led us to believe this was a malignant osteogenic tumor. Full knowledge and the correct diagnosis of ossifying fibroma should have prevented an unnecessarily extensive operation for this benign lesion.


The major histocompatibility complex of rhesus monkeys, RhL--A. VII. Identification of five new serologically defined antigens. Five new serologically defined (SD) tissue antigens of rhesus monkeys are described. Results of a population study and a segregation analysis in families were consistent with their control by the major histocompatibility complex (MHC), as alleles of the two previously established SD loci of RhL--A. The number of identifiable SD specificities of the rhesus monkeys' MHC is now twenty-five, thirteen controlled by the SD1 locus and twelve by SD2. The recombination frequency between SD1 and SD2 is estimated to be 0.3%. No evidence of a third SD series, as analogue of the human HLA--C locus, has yet been found.


The Euiryong experiment: a Korean innovation in household contraceptive distribution. Although contraceptive practice has increased substantially in Korea as a result of a strong national family planning program, surveys indicate the existence of an additional unmet demand. A number of obstacles tend to limit availability of family planning services and supplies. The effects of total availability are being tested in a three-year experiment in household contraceptive distribution, for which an exploratory study was carried out in 1975 in Euiryong gun. Three distribution systems were tried in three areas of Euiryong, each enlisting local women to canvass and distribute pills and condoms (and refer those desiring IUDs or sterilization to physician). Results of the preliminary test showed that household distribution was culturally acceptable and administratively feasible and that it did increase contraceptive use. Cost-effectiveness was considered to be within the range of the national program. The most successful of the three distribution systems is being applied in the main study, begun late in 1976 in Cheju province.


Measuring the effectiveness of contraceptive marketing programs: Preethi in Sri Lanka. The Preethi marketing program resulted in sales of more than 11 million condoms during its first 33 months, multiplying Sri Lanka's annual per capita condom use by a factor of five. Estimates for 1974 show 144,000 new acceptors (8% of married women of reproductive age), totaling 50,000 couple-years of protection. It is also estimated that more than half of the nation's 1.8 million couples of childbearing age were educated about the function of a condom. Unit costs were low for this new, nationwide program: about US $2.00 for each new acceptor; 6.00 dollars for each couple-year of protection; and 0.09 dollars for each couple educated. The program's success suggests that a social marketing approach can advance family planning at a relatively low cost.


Sympathetic regulation of cephalic blood flow. Blood flow to bilateral tissues (cranial and extracranial) was studied by means of the particle distribution method in two groups of anesthetized dogs (five using 25-mu radioactive microspheres, six using 15-mu microspheres) and five anesthetized stumptail Macaques monkeys (8-mj spheres) during unilateral sympathetic stimulation. The stimulatory parameters were adjusted to produce maximum pupillary dilatation. In the five dogs hemispheric and regional cerebral blood flow decreased but not significantly. Flow to the extracranial tissues decreased 82%. Hemispheric brain blood flow averaged 0.70 ml/min/gm for Paco2 of 40 mm Hg. In the six dogs sympathetic stimulation did not significantly decrease cerebral blood flow but decreased flow to extracranial tissues (72.3%). At an average Paco2 of 33.2 mm Hg, hemispheric blood flow to the unstimulated side averaged 0.51 ml/min/gm. In the five monkeys findings were essentially the same as those observed in the dogs. The hemispheric blood flow averaged 0.36 ml/min/gm on the nonstimulated side for an average Paco2 of 36.6 mm Hg. Under the conditions studied, electrical stimulation of the cervical sympathetic nerves does not appear to modify regional or total brain blood flow in dogs and Macaques monkeys. The vascular response in oral and other extracranial tissues is very dramatic, however.


Stochastic analysis of 133xe clearance for determining regional cerebral blood flow in a primate model. A technique for stochastic analysis of 133Xe washout using a computer-assisted Anger camera is described. The technique produces functional maps of both regional cerebral blood flow (rCBF) and error in rCBF. The calculational limitations of the technique are discussed and an experimental estimate made of the physical limitations associated with the low energy photon emitted by 133Xe. The method is demonstrated in a rhesus monkey model before and after surgical occlusion of the middle cerebral artery.


The type and screen: a safe alternative and supplement in selected surgical procedures. For the year 1975, we examined 12,848 blood specimens using the type and screen as well as the crossmatch and detected 283 antibodies in 247 patients. Our screening reagent red blood cells were able to detect 96.11 per cent of these antibodies. If the antigen frequencies corresponding to those antibodies not detectable by our screening reagent red blood cells are taken into consideration. i.e., the incompatibility frequencies, the type and screen can be shown to be 99.99 per cent effective in preventing the transfusion of incompatible blood. Therefore, we believe that the type and screen may be safey substituted for the routine two-unit crossmatch in those operative procedures usually not requiring transfusions. Adoption of this approach would reduce patient charges, provide for more efficient distribution of our limited blood supplies, and allow for more effective utilization of blood-bank technologist time.


Cell cycle distributions, growth characteristics, and variation in prolactin and growth hormone production in cultured rat pituitary cells. Clonal strains of rat pituitary tumour cells (GH3 cells) spontaneously produce and secrete prolactin and growth hormone. Chromosome analysis and DNA ploidy measurements revealed that the GH3 cells in the present study were triploid and had a decreased chromosome number compared to the parent strain. Monolayer cultures of these cells grow exponentially for 6-7 days with a mean doubling time of 54 h. Cell cycle distributions and phase durations were determined by micro-flow fluorometric measurements of cellular DNA content combined with computer calculations. During exponential growth the cell cycle distribution did not change (65.4% cells with a G1 phase DNA  content, 24.9% with an S phase DNA content, and 9.7% with a (G2 + M) phase DNA content). Counting of mitoses gave 1.4% cells in M phase. The 3H-Tdr labeling indices were determined by autoradiography, and the results were in good agreement with the number of cells in S phase as calculated by micro-flow fluorometry. The phase durations were: Ts=15.9 h, TG2=6.2 h, TM=1.1 h, and TG1=30.9 h. TS and TM calculated from 3H-Tdr labeled and Colcemid treated cultures gave corresponding results. In plateau phase cultures the number of cells with a G1 DNA content increased to 80% and the number of cells with an S phase DNA content decreased to between 5% and 10%. The specific production of prolactin and growth hormone determined by radioimmunoassay showed two and four-fold increases respectively, during exponential growth. The hormone values decreased to initial or subinitial values (day 2 values) when approaching plateau phase. We conclude: that changes in the cell cycle distribution of the cell population cannot be responsible for the spontaneous alterations in hormone production during growth and that most of the hormone-producing cells must be in the G1 phase.


Mitosis of type B alveolar cells in the early hyperplastic response to Freund's adjuvant. Numerous areas of granulomatous inflammation develop in the lungs of rabbits following the intravenous injection of Freund's complete adjuvant (FCA). Within a few days after FCA injection, hyperplasia of type B (type I) alveolar cells is present on the surface of the septa in which an inflammatory reaction is developing. Mitosis of type B cells is detected 12 h after FCA injection and is common over the next 120 h. In addition, there are morphologic changes that are consistent with migration of these cells. The type B cells in mitosis extend across alveolar septa as well as along the alveolar surface. The extension of type B cells through alveolar septa is not limited to cells in mitosis, but is also observed in non-mitotic type B cells. Stimulation of mitosis and hyperplasia of type B cells is discussed in relation to the focal tissue injury and inflammatory response.


Pancreatic islets subjected to different concentrations of glucose in vitro. A study with special regard to mitochondrial changes. Isolated pancreatic islets of mice and gerbils were cultured for 6 days at low (2mM) or high (20mM) concentrations of glucose after which they were studied using qualitative and quantitative electron microscopy, histo- and microchemistry, and X-ray microanalysis. Compared with the islets cultured at high glucose, those subjected to low glucose exhibited enhanced succinate dehydrogenase activity, a decreased content of adenosine triphosphate, and an increased volume of B-cell mitochondria which often were rounded or oval.


Scanning electron microscopic investigations of acute leukemia. Twenty cases of acute lymphoblastic leukemia (ALL) in children and adults were investigated at different tissue localizations by scanning electron microscopy. ALL was divided into cases with or without strong paranuclear acid phosphatase activity. ALL showed very similar surface morphology irrespective of the type of ALL or the tissue localization. ALL is, however, strikingly different in some from other childhood leukemias and lymphomas, as well as from activated T-lymphocytes in infectious mononucleosis. The results indicate that the surface morphology of leukemic cells is a stable cytologic parameter, if certain technical prerequisits are fulfilled. Further criteria may thus be added to the panel of known cytologic, cytochemical and functional parameters.


High-dose irradiation in the pig small intestine. Histoenzymology and electron microscopic study. The early and late effects of a single high-dose irradiation (100 rad) in the pig small intestine have been studied by histoenzymology and electron microscopy and related to some functional data. 1) The initial atrophy induced by the irradiation appears late (on the 6th day), compared to other species. This is due to the fairly long regeneration time of the villi epithelium in the pig. 2) The initial lesions are similar to those observed in different experimental models (nuclear alterations, karyolytic bodies, etc.). They particularly involve the crypts, and are specially focused in the undifferentiated cells of GS phase or mitosis, but also in goblet and Paneth's cells. 3) The villi regeneration, over on the 23rd day, is preceeded by an active mitotic phase which first renews the undifferentiated cells. This mitotic activity, reaching its highest value on the 16th day, goes on during the whole regeneration period itself. 4) At the beginning, this regeneration is denoted by the high esterase activity of the crypt collar. It appears in many goblet cells and also in some absorptive cells which show, at once, some of the enzymatic activities of the striated border. However, for a short period, lipid absorption is quantitatively reduced. This is connected with the temporary cell immaturity (up to the 20th day) and to the poorly developed rough endoplasmic reticulum and Golgi apparatus. 5) Further on, the persistence of a malabsorption syndrome (lipids, calcium) is not connected, for the main point, with modifications of the morphology or the cytology of the villi (in spite of the abnormally high number of goblet cells and the presence of few pathologic absorptive cells). It is, in fact, related to the persistence of an inflammatory state of the lamina propria associated with an exudative enteropathy. The meaning of this last finding is not clear: it could depend on a primary infectious state due to the modifications of the endoluminal intestinal flora, or, rather, on a secondary infection supported by the trophic epithelial disturbances induced by a continuous vascular dyshoria due to the irradiation.


The role of cellular locomotion in leukemic infiltration. An organ culture study on penetration of L 5222 rat leukemia cells into the chick embryo mesonephros. The significance of cellular locomotion for leukemic infiltration was investigated using L 5222 rat leukemia cells. Previous cinemicrographic studies have shown that these cells are able to locomote only after formation of a uropod-like posterior extension. This characteristic locomotive configuration of L 5222 cells is easily recognizable in scanning electron micrographs and appropriate sections. Leukemia cells were inoculated on slices of chick embryo mesonephros incubated for 24h; at this time the fragments are completely encapsulated. Leukemic infiltration is found to begin within the first 2 h and to increase gradually up to the end of the observation period at 72 h. Spread of leukemia cells occurs mainly in the intertubular spaces; the tubular epithelium is only rarely affected. In all stages of infiltration, L5222 cells with the characteristic locomotive configuration are frequently recorded. Besides this strong although indirect indication for the significance of locomotion, further evidence was provided by experiments performed at 25 degrees C and 18 degrees C. In accordance with the previous cinemicrographic finding that at these temperatures L 5222 cells are unable to produce their posterior extension, no leukemic infiltration mesonephros fragments is recognizable at subnormal temperatures.


[Inhibition of cell viability by cellular debris. Model experiments to study tissue damage (author's transl)]. Some aspects of tissue damage as it may accompany shock are investigated in an in vitro model system. Some effects of cell debris obtained by sonication of BHK 21 cells on viable cultures of freshly dissociated cells of the same line are evaluated. After 24 h incubation on a coverglass, the area covered by cell nuclei per square millimeter was determined. Spreading of viable cells is inhibited by the cell debris. In this way, growth and viability are also impeded. After 24 h the mitotic index in controls and treated cell-cultures is the same. The inhibition is exhibited as well by the supernatant as the pellet of a centrifuged suspension of sonicated cells. The growth retardation is counteracted by the polyvalent protease inhibitor Trasylol (50 KIE/ml), when the whole suspension or its pellet are added to the culture, but not when the supernatant affects the cells. These results indicate that the injurious substance is not a protease. The protective action of Trasylol may be due to a stabilisation of lysosomes. Tissue injury is often accompanied by alterations in cellular adhesiveness to substrate and in growth rate. The system used here offers a simple model to study the influence of necrotic tissue on cell viability as well as its pharmacological susceptibility.


Naturally occurring human antibodies with specificity for light chains of immunoglobulins. Human sera of different categories were screened for antibodies against IgA. A surprisingly high incidence of antibodies was observed. All of these antibodies were of restricted specificity, i.e. able to react with one or a few individual IgAs from a panel of eight myeloma proteins used in the screening. In one serum of a patient with selective IgA deficiency an antibody against the allotype A2m(1) was found. Some of the antibodies were shown to belong to the IgG class. The IgA, IgG and IgM content of the antibody-containing sera was generally increased. Two different antibodies which both reacted with the same individual IgA were studied in detail. The antigen involved could not be detected in normal Caucasian sera but was detectable in some sera of patients with IgA, IgG, IgM or IgD paraproteinemia. The antigenic site was located on the light chain of the Ig molecule but no correlation with either the light chain type or the genetically determined Inv factor was evident.


Investigations of the antiviral activity of some nitroso-urea derivatives. Inhibitory action of the IOB-252 nitroso-urea derivative on vaccinia virus incell cultures. The nitroso-urea derivative IOB-252 was administrered in monkey kidney cell cultures in a concentration of 40 mug/ml 24 hours before inoculation of vaccinia virus and maintained afterwards in a concentration of 25 mug/ml. The drug inhibited vaccinia virus multiplication, hemagglutinin synthesis and late cytopathic effect, but did not prevent early cytopathic lesions. IOB-252 inhibited the synthesis of interferon initiated by a viral inductor and blocked the antiviral effect of an exogeneous interferon. The mechanism of action of the drug is discussed.


Use of discriminant analysis in relating maternal anti-D levels to the severity of haemolytic disease of the Newborn. The automated assay of maternal anit-D levels has been compared with manual methods and correlated with the severity of haemolytic disease of the newborn using discriminant analysis. The automated assay of anti-D proved to be marginally better than manual techniques in predicting the need for amniocentesis. The level at which amniocentesis should be considered has been calculated to be 4IU/ml of maternal serum.


Selective depression of blood group antigens associated with hereditary ovalocytosis among melanesians. Recessively inherited ovalocytosis in coastal Melanesians is associated with widespread, but selective, depression of blood group antigens in homozygotes, who comprise about 15% of these populations. It is suggested that a membrane anomaly exists, and that the series of depressed determinants all depend, for their full expression, upon the same membrane component(s), the proper synthesis of which is being genetically affected. Affected antigens would thus be associated by position and/or structure. Antigens subject to depression include IT, IF, LW,D,C,e,S,s,U,Kpb,JKa,JKb,Xga,Wrb,Scl and Ena, which are simultaneously affected when present on oval cells. Reactivity of A1,ID,i,P1,M,N,Lub,k,Fya,Coa, Vel and Gea appears to be within the normal range on depressed cells, as does sialic acid content. Indirect evidence suggests that Z (associated with S and s) is among the depressed series, while NA and Leb are not. High H variants, common among Melanesians, seem absent among depressed bloods, and when such variants were excluded, H, A and B did not appear subject to depression. The distribution pattern of ovalocytosis suggests that it may confer some selective advantage in the tropical coastal environment. The findings also have implications concerning population genetic work in New Guinea.


[Clinical, histological and electron microscopic findings in neurofibromatosis (Recklinghausen's disease) occurring in childhood (author's transl)]. A follow-up study was carried out of the clinical symptoms and the radiological and histological alterations in five cases of neurofibromatosis (Recklinghausen's disease) with onset during early childhood. The clinical manifestation of the disease was predominantly restricted to the face. In the histological ultrastructural investigation different types of neurofibroma were detected (plexiform neurofibroma, argyrophilic neurofibroma and diffuse neurofibrma). Preliminary results are presented on the basis of a correlation between the clinical findings and the histological types of neurofibroma with special reference to the demarcation of the tumours, recurrence following surgical removal and the prognosis as to the clinical course of the disease. Nevertheless, definite conclusions will be possible only by continuous observation of a larger number of patients by means of standardized clinical, radiological and histological methods of investigation.


Metabolic disposition of 6-chloro-5-cyclohexyl-1-indancarboxylic acid (TAI-284), a new non-steroidal anti-inflammatory agent, in rhesus monkeys. 1. After oral administration of 6-chloro-5-cyclohexyl-1-indan[14C]carboxylic acid (TAI-284) to rhesus monkeys, the plasma concn. reached a plateau at 2 h, which persisted for 4 h and then declined with an approximate half-life of 24 h. More than 92% of the plasma radioactivity was derived from unchanged TAI-284. The plasma concn. of the ulcerogenic metabolite, 6-chloro-5-(cis-3'-hydroxycyclohexyl)-1-indancarboxylic acid (metabolite IIb), was much lower in monkeys than in rats. 2. In monkeys, elimination of the ingested radioactivity was complete in 96 h, the excretion being almost equally divided between urine and faeces. This excretory pattern was similar to that in rats. The major urinary metabolites in monkeys  were TAI-284, 6-chloro-5-(trans-4'-hydroxycyclohexyl)-1-indancarboxylic acid (metablite III) and glucuronides of TAI-284 and its oxo or hydroxy derivatives (metabolite VI), whereas those in rats were dihydroxy derivatives of TAI-284 (metabolite V) and VI. Unchanged TAI-284 accounted for only a small part of the faecal radioactivity in monkeys and rats. 3. Both in monkeys and rats, some of the dose of radioactivity was excreted in bile to enter into entero-hepatic cycling. Biliary excretion of metabolite IIb was markedly smaller in monkeys than in rats. 4. These metabolic findings are discussed in relation to the variation in the TAI-284-induced intestinal ulceration between monkeys and rats.


[Standard methods of blood group serology--state and trends of development]. The notion of transfusion serology comprises also serologic examinations in connection with transfusions of thrombocytes and leucocytes. The minimum demands of serological methods in the German Pharmacopoeia 7 (DAB 7) obligatory nowadays before transfusions of full blood and concentrates of erythrocytes should be changed and enlarged as follows: Obligatory carrying-through of the bed-side-test, inclusion of the ferment- and/or Coombs-test as major test into the cross typing, abolition of the minor test. In connection with the transfusions of leucocytes and thrombocytes determinations of the HLA-antibodies and cross typings are practicable in the institutions of the transfusion service. Transfusion must principally be striven for, taking into consideration the HLA-typing, but at present it is only limitedly possible. The search for donors among relations by blood increases the chances of the serological compatibility. Necessity and scale of an "emergency serology" still need discussion. Optimum haemotherapy is possible only then, when clinics and transfusion service work together in very close coordination.


[Hemobilia, a rare and dangerous postoperative complication]. 3 cases of severe postoperative hemobilia are reported, one patient with an echinococcus cysticus of the liver, two others after surgical procedures on biliary tract. Diagnostic means as cholangiography, coeliacography, scanning of the liver and endoscopic retrograde cholangiography were not possible because of the massive bleeding. In those cases, if no other sources of bleeding are found, only esophago-gastro-duodenoscopy can leed to the correct diagnosis. In gastrointestinal bleeding after surgical manipulation on the biliary tract, the duodenum and the pancreas, hemobilia is a possible cause.


The function of the epiglottis in monkey and man. In stumptail monkeys from birth to adulthood, and in very young human infants, the epiglottis serves to guide the larynx upwardly behind the soft palate so it can lock into the nasopharynx and remain there during respiration. After early infancy in man the attainment of a larynx-nasopharynx connection is uniquely lost, causing the epiglottis to have no essential function.


[Acute pancreatitis--the current state of surgical treatment]. In the beginning of this century the "early operation" in acute pancreatitis was widely used. The irreversibility of the local necrosis and the failure of conservative treatment again lead to the application of this procedure. Early operation is indicated when the pancreatitis shows a more severe degree and when there is no success on conservative therapy or even deterioration in the patient's condition. Early operation means digital removal of the necrosis and/or resection of the pancreas, procedures on the biliary tract, methods for suppression of the secretory activity and installation of jejunal fistulas for external feeding. The mortality rate of partial necrotizing pancreatitis was lowered by this means. In case of total necrosis the mortality was still about 100%. In the postacute stage complications such as sequestration, abscess formation, sepsis, hemorrhage, fistulas can arise. In some of these complications only a "delayed operation" is successful. If a biliary acute pancreatitis was not early and definitively treated, the causative diseases of the biliary tract have to be cured in the postacute stage.


[Ultrasonic study of fetal dysmaturity: hypertension, diabetes and Rhesus-immunization (author's transl)]. Using ultrasonic A- and B-scan equipment (Kretz-Technik), 80 pregnancies with chronic placental dysfunction were investigated: 34 cases with hypertension, 24 cases with diabetes and 22 cases with rhesus immunization. In addition to biparietal diameter (A-scan), the direct and transverse diameter, the circumference and the area were estimated on B-scan displays of the occipito-frontal plane and the largest cross-sectional plane of the abdomen. 15 parameters of fetal growth and body composition were compared with normal standards. The significance of the different methods in the diagnosis of fetal dysmaturity was demonstrated.


[Contributions to the life-cycle of Frenkelia. III. The sexual development of F. clethrionomyobuteonis in the buzzard (author's transl)]. 8 buzzards (Buteo buteo) were infected orally with cysts of Frenkelia clethrionomyobuteonis of the bank vole (Clethrionomys glareolus). Their intestines were searched for developmental stages of Frenkelia 21 and 24 h and 2, 3, 4, and 5 days post infection. After 21 and 24 h male and female gamonts could be detected within epithelial cells of the villi of the first half of the small intestine. The microgamonts contained 10-14 microgametes. The macrogamonts which measured on an average 11,1 X 9,8 mum in Giemsa stained smears developed into very thin-walled oocysts measuring in fresh preparations on an average 15,8 X 11,7 mum on day 3 after infection. The oocysts were located between the lamina propria and the epithelial lining of the distal third of the villi. They began to sporulate on day 5 and the first sporocysts were excreted 7 and 8 days post infection. Schizonts and schizont-like stages could not be observed in the developmental cycle in Buteo buteo.


Light and electron microscopical study on sarcocysts from muscles of the rhesus monkey (Macaca mulatta), Baboon (Papio cynocephalus) and Tamarin (Saguinus(=Oedipomidas) oedipus). Sarcocystis cysts from muscles of monkeys (baboon, tamarin and rhesus monkey) were studied by means of light and electron microscopy. The differences in the morphology of the cyst wall and parasites clearly indicate that the three monkey species examined were each parasitized by at least a specific Sarcocystis species being not identical with S. nesbitti or S. kortei. The large numbers of cysts found within the muscle fibres point out the important role that have these monkeys as intermediate hosts in the life cycle of Sarcocystis species, where the final hosts are still unknown.


[On the transplacental induction of tumours by N-ethyl--N-nitrosourea in different species (author's transl)]. The transplacental activity of N-ethyl-N-nitrosourea (ENU) was tested in rats, rabbits, Syrian golden hamsters, Dzungarian dwarf hamsters, guinea pigs, dogs, and rhesus monkeys. In the offspring of rats, multiple tumours of the central and peripheral nervous system were found in 100 per cent, whereas in rabbits kidney tumours developed. In Syrian golden hamsters, the application led mostly to neoplasms of the thyroid gland. Dzungarian dwarf hamsters and monkeys prooved to be resistant. 9 out of 15 dogs died shortly after birth. In two dogs a carcinoma of the thyreoid gland and one of an ovary were found. Because of an infection, the experiments with guinea pigs were to be interrupted untimely. Therefore, a final answer is impossible. Own results were compared with the findings of other authors. The significance of the different susceptibility in distinct species is discussed.


[Absorbable suture material in the surgery of the biliary tract (author's transl)]. Conventional unabsorbable suture material can lead to gall salt precipitation and thus to gall stone formation. Catgut segments may cause identical sequelae if they are displaced into the lumen of the biliary tract under certain conditions. The reaction of polyglycolic acid (PGA) as well as of polyglactin material was tested under in-vitro conditions. PGA material disintegrated within 9 weeks; precipitation of gall salts was not observed. Polyglactin samples showed stable durability up to 22 weeks under the same conditions; firmly adherent small concrements could be demonstrated. In accordance with these observations, PGA material seems to be the most appropriate suture material for the surgery of the biliary tract at the time being.


[Treatment results in supervoltage therapy of malignomas of the collum uteri]. Based on a material of 136 patients with cervix cancer the results of radiation therapy partially combined with intracavitary radiotherapy are discussed. The 5-year survival rates are accordanted with good results of other authors. The 5-year survival rate is 17,6% in progressive cases with tumour invasion in the urinary bladder, from has to derived, that by application of megavolt therapy this group of patients is an indication for radiation therapy under curative terms.


[Results of phage typing of Salmonella typhi and Salmonella paratyphi-B in the years 1970-1973 (author's transl)]. Between 1.1.1970 and 31.12.1973 3639 strains were typed with the aid of phage typing. Of these strains 1793 belonged to S. typhi and 1846 to S. parathyphi-B. 40 S. typhi phage types were found. 9 of these occurred in a frequency of more than 1% (relevant to foci). These were E1 (25.7%) (of this E1a 19.7%, E1b 5.9%), A (16.6%), F1 (7.5%), D1 (59%), C1 (5.4%) D2 (2.3%), 46 (2.1%), 28 (1.9%). Among S. paratyphi-B 24 phage types resp. varieties were found, 14 of these occurred in a frequency of more than 1% (relevant to foci). The phage types comprised Taunton (36.8%), 1 m.c. (10.3%), 3aI m.c. (7.5%), B.A.O.R. (6.8%), 3 a m.c. (4.9%), Dundee (4.6%), 3 aI var. 1 (4.6%), Beccles m.c. (2.4%), 3 b m.c. (2.3%), 3 aI var. (2%), 1 var. (1.8%), 3 aI var. 4 (1.1%). As far as it came to be known the epidemiological relations and particularities of the different S. typhi and S. paratyphi-B phage types are discussed. In th period of this report only one larger epidemic outbreak of S. paratyphi-B (type Taunton) occurred. Possibly the cause of this was contaminated milk.


Immunosuppressive effect of Pseudomonas aeruginosa endotoxin on lymphocyte transformation in vitro. In order to prove the immunosuppressive activity of an endotoxic fraction from pathogenic Ps. aeruginosa, the lymphoblastic transformation test was used. The results have shown that lymphocytes cultured in presence of PHA and endotoxin have a decreased rate of DNA synthesis and oxygen uptake. On the contrary, there seemed to be a slight relative increase of RNA and protein synthesis as compared with PHA-transformed cells.


[Studies on serological classification of Pseudomonas aeruginosa using the indirect fluorescent antibody technique (author's transl)]. An application mode of the indirect fluorescent antibody technique is described which allows the differentiation of soma and flagella of Ps. aeruginosa cells on the morphological and serological level simultaneously and the determination of the topic specificity of Ps. aeruginosa antisera. Antisera prepared by immunization of rabbits with formalinized semisolid agar cultures react with somatic and flagellar antigens (anti-OH-sera), while antisera made with heated cultures strain somatic antigens exclusively (anti-O-sera). Anti-OH-sera absorbed by heated cultures of the strain used for immunization lead to selective fluorescent staining of flagellar antigens (anti-H-sera). The reaction between somatic antigens and antisomatic antibodies is inhibited by coating substances which are removed by washing the cells. The masking effects of thermovariable and correlates with the viscosity of the cell suspension. The somatic antigens of washed cells are thermostabile, whereas the flagellar antigens are destroyed after heating at 60 degrees C. The strains representative of serogroups 0:1-0:12 of Habs show numerous uni- and bilateral relationships of the somatic antigens. However, group-specific reacting anti-O-sera are obtained by dilution of absorption of the overlapping antisomatic antibodies. The flagellae of the representative strains belong to two flagellae types: one type shows a complex, the other a uniform antigen structure. They do not include all flagellar antigens existing in Ps; aeruginosa;


Effects of the common protective antigen (OEP) and toxoids of protease and elastase from Pseudomonas aeruginosa on protection against hemorrhagic pneumonia in mink. The effects of common protective antigen (OEP) of Pseudomonas aeruginosa strain N10 (serotype 5) and OEP plus toxoids of protease and elastase from P. aeruginosa strains IFO 3080 and IFO 3455 were studied during an enzootic of hemorrhagic pneumonia caused by P. aeruginosa serotype 3 in mink. The overall mortality rate in non-vaccinated mink was 24.8% (524 mink). It was highest in male kittens, followed by female kittens and adults. OEP (1,000 millimicrong) plus toxoids (each 1,000 millimicrong of protease toxoid and elastase toxoid) was significantly protective in every stable or farm regardless of sex or age. It was also effective in a stable where the vaccine was administered 12 days after the onset of the disease. OEP (1,500 millimicrong) alone produced a similar effect in a majority of mink, but was less effective in some stables. OEP plus toxoids was significantly more effective than OEP alone in protecting mink against hemorrhagic pneumonia due to P. aeruginosa.


[Electronenmicroscopic Studies on Cells of Listeria monocytogenes Treated with Enterocin (author's transl)]. Purified enterocin E1A, a bacteriocin produced by Streptococcus faecium E1, had a strong bactericidal activity on susceptible cells of Listeria monocytogenes. Electronmicroscopic observation of thin sections of L. monocytogenes, treated with enterocin E1A at a concentration that gave 0.1% survivors, revealed that the predominant features of morphological alterations concern the partial dissolution of the cell content and the damage of the cell envelope which enabled an efflux of cell-material. Not frequently intact protoplasts and greatly elongated cells were observed.


On the growth of Brucella species in presence of erythritol in defined and undefined media and amniotic fluid of human, cow and sheep. Different concentrations of erythritol (25-1000 microng/ml) in defined medium were shown to enhance the growth of 75.00 to 91.66 per cent of Brucella abortus and 69.23 to 100.00 per cent of Brucella melitensis strains studied. Compared to these figures only 13.04 to 60.86% (in tryptose broth), and 41.40 to 62.50% (in glycerol dextrose broth), of Brucella abortus strains, 25.00 to 83.30 per cent (in tryptose broth) and 83.30 to 100.00 per cent (in glycerol dextrose broth) of Brucella melitensis strains showed increased growth over the control. 82.20 per cent of amniotic fluid samples from humans showed anti-brucella activity with lytic zones varying from 7-19 mm. Amniotic fluid from cows and sheep had no antibrucella activity.


Comparative analysis of the antigens of M. tuberculosis H37RV with various mycobacterial antigens. Comparative immunoelectrophoretic and immunodiffusion analyses have indicated that H37Rv shares a number of antigens with other mycobacteria. Some of these shared antigens are polysaccharide in nature wheras others are proteins. The two antigens that this organism shares with M. smegmatis are primarily polysaccharides and so is the antigen that it shares with BCG ribosomal fraction. With M. kansasii, the H36Rv shares both polysaccharide and protein antigens, the polysaccharide antigens being the same ones that are shared by M. smegmatis and BCG. On the other hand, the H37Rv appears to share only protein antigens with M. marinum and none with M. leprae. It is suggested that the antigen that is shared between M. kansasii and H37Rv could be specific to these two strains and the one that is shared between M. kansaii, H37Rv and BCG ribosomal fraction could be related to the virulence potential of the individual species.


Endocrine morbidity in adults treated with cerebral irradiation for brain tumours during childhood. Hypothalamic-pituitary function was assessed in 20 adult subjects who were treated with cerebral irradiation for brain tumours during childhood between 8 and 32 years earlier. Nine patients showed impaired growth hormone (GH) responses to hypoglycaemia, of whom, 7 are below the third centile for standing height. All GH deficient subjects received more than 2950 rads to the hypothalamic-pituitary axis with a maximum dose of approximately 5000 rads being used in one case. Three subjects have an elevated basal serum thyroid stimulating hormone (TSH) level and 2 of these show an exaggerated TSH response to thyrotrophin releasing hormone (TRH) but no patient was clinically or biochemically hypothyroid. The rest of hypothalamic-pituitary function was essentially normal. This study shows that multiple pituitary hormone deficiencies do no develop with time when the radiation dose is below a critical level. Thus it appears that there is a gradation of radiation damage to the hypothalamic-pituitary axis which is dependent primarily on the dose received rather than the time interval after radiotherapy.


Effects of dipyridamole on sodium and potassium content of human red blood cells. The effects of dipyridamole on potassium and sodium content of human red blood cells from normals or from patients with hypochromic anaemia, and of normal red cells pretreated with menadione, have been studied. Dipyridamole added to the incubation medium decreases the loss of potassium and the accumulation of sodium in all three types of red cells incubated at 37 degrees C for 24 h, either with or without calcium. The possible mechanism underlying these effects of dipyridamole is discussed.


Peripheral blood lymphocytes in systemic lupus erythematosus. Relation to activity. Peripheral blood lymphocytes from 20 patients with systemic lupus erythematosus (SLE), 3 patients with drug-induced lupus and 20 normal controls were studied. The absolute number of E-rosette-forming cells (ERFC) and surface immunoglobulin-bearing cells were determined during active and inactive stages of the disease. An attempt was made to establish the relationship between the number of ERFC and the clinical stages of the disease on one hand and treatment on the other. A decrease in ERFC was observed in all SLE patients, but it was most prominent in patients with active disease. No correlation was found between treatment and the decreased numbers of ERFC.


Cold agglutinins in a case of chronic lymphatic leukaemia. A study of the lymphocyte surface. A case of chronic lymphatic leukaemia with cold agglutinins is presented in which peripheral blood lymphocytes of varying maturity appeared to possess T- and B-cell markers. A cold agglutinin IgM in type is identified in the serum and at the cell surface. This seems to be responsible for the spontaneous rosetting of sheep red blood cells (SRBC); A single clonal origin of these cells is suggested with maturation arrest. It is also suggested that with configurational change in lymphocyte surface cryoglobulins may sometimes produce spontaneous rosetting with SRBC.


Peptichemio: A new oncolytic drug in combination with vincristine and prednisolone in the treatment of non-Hodgkin lymphomas. Peptichemio, a new oncolytic drug with alkylating and antimetabolic properties was employed in combination with vincristine and 6-methylprednisolone (PVP) for the treatment of diffuse non-Hodgkin's lymphomas (NHL), stages III and IV. 52 of 66 patients who entered the PVP protocol were considered evaluable: the overall remission rate in diffuse lymphocytic poorly differentiated lymphomas (DLPD) was 56.6 and 55% in diffuse histiocytic lymphomas (DHL). Median duration of complete remission was 16 months in DLPD and 13 months in DHL. Dramatic results were obtained in "oncologic emergencies," such as mediastinal involvement and spinal cord compression. Bone marrow depression from PVP was moderate and never caused discontinuation of therapy. According to these results the PVP protocol would appear susceptible of offering a major contribution to the chemotherapy of diffuse NHL.


Inherited platelet abnormalities associated with low factor VIII activity in the same family. Six of eight examined members belonging to two generations of the same (NEG-TUR) family were shown to have functional changes in platelets and/or a moderate decrease of factor VIII activity (FVIII:C) in plasma, with normal values of factor VIII-related antigen (VIII R:AG). Platelet defects (mainly a reduced PF3 availability, present in five patients) and factor VIII decrease were combined differently in individual members. Only two male members with both the PF 3 and FVIII:C defects had moderate haemorrhagic symptoms following traumatic injuries. One of them had also an absent adhesiveness to glass, the other one an absent adhesiveness to collagen and a reduced platelet aggregation by ADP and by collagen. Bleeding time, platelet function tests (in the other members), and routine coagulation tests were within normal range; ristocetin aggregation was also normal in all members. We think that two inherited defects, a mild haemophilia A and a "sui generis" thrombocytopathy, co-exist in this family.


Influence of cytostatics on some platelet functions in vitro. V. Hydroxyurea. Hydroxyurea added to citrated platelet-rich plasma in vitro did not influence the aggregation of the platelets, their adhesion to glass, their release of aggregating activity, platelet factor 4 or availability of platelet factor 3. Neither did it have any effect on the uptake of 14C-serotonin, the reptilase clot retraction or the coagulation system.


Scanning electron microscopic study of leukemic human B lymphocytes. Peripheral blood lymphocytes from patients with chronic lymphocytic leukemia (CLL), lymphoplasmacytoid lymphoma, centrocytic lymphoma and hairy cell leukemia were studied by scanning electron microscopy (SEM). In general, SEM revealed rather homogenous cell populations. Most lymphocytes displayed a moderately villous surface architecture, although smooth surfaces predominated in 3 cases with CLL and in 1 case with lymphoplasmacytoid lymphoma. Hairy cells showed surface features of both lymphocytes and monocytes. The results indicate that leukemic B and T lymphocytes cannot be distinguished by SEM alone.


Postoperative platelet function in patients on small subcutaneous doses of heparin. Several platelet function tests were performed on 31 patients undergoing major operations, who recieved prophylactically small subcutaneous doses of heparin. A group of 15 similar patients without heparin served as controls. It was found that postoperatively in both groups (a) the platelet retention in glass bead column was significantly increased (p less than 0.001), (b) the platelet aggregation by ADP 1 micronM was slightly increased, (c) the collagen-induced aggregation, ADP release and the bleeding time remained unchanged and (d) the platelet counts decreased in the first 2 postoperative days and increased thereafter. There was no difference between patients on heparin and controls.


Antihaemophilic factor A activity, F VIII-related antigen and von Wilebrand factor in hepatic cirrhosis. F VIII activity, F VIII-related antigen and von Willebrand factor were measured in 46 patients with hepatic cirrhosis and in 30 normal individuals. These parameters were significantly higher in hepatic cirrhosis than in the controls. Linear relationships between F VIII activity and F VIII-related antigen and between F VIII-related antigen and von Willebrand factor were found in patients with hepatic cirrhosis as well as in normal individuals. However, in both groups no relationship between F VIII activity and von Willebrand factor was present. The existence of a low-grade intravascular coagulation in hepatic cirrhosis may be postulated but more information about the metabolism of F VIII protein is needed before such a statement can be proven.


Chronic myelogenous leukemia with elevated leukocyte alkaline phosphatase, positive indirect Coombs' test, neutrophilic leukocytosis and unusual cytogenetical findings. An unusual case of chronic myelogeous leukemia (CML) is reported which was characterized by leukocytosis without a shift to the left, elevated leukocyte alkaline phosphatase, positive indirect Coombs' test, anemia and thrombocytosis, as well as the absence of hepatosplenomegaly. The diagnosis of CML was ascertained by the presence of Philadelphia chromosome with translocation of its deleted arms on the short arms on the short arms of a chromosome No. 6. The possible relationship between the chromosomal aberration and the unusual hematological and clinical features of this case is discussed.


Erythrocyte delta-aminolaevulinic acid dehydratase, urinary porphyrins and porphyrin precursors in iron deficiency anaemia. In 20 iron deficient patients and 21 normal controls the activity of the enzyme delta-ALA dehydratase of erythrocytes was assayed. In addition the urine porphyrins and porphyrin precursor excretions were measured. It was found that in sideropenic patients the erythrocyte delta-ALA dehydratase activity was almost constantly higher than in normals; the difference of the mean values being statistically significant (p less than 0.005). A significant diminution of delta-ALA (p less than 0.0025) urine excretion was observed, whereas the urine excretion of PBG, CP and UP was found within the normal limits. The results are compared to those reported by other authors.


Loss of the Y chromosome from bone marrow cells of males with myeloproliferative disorders. Report of two cases and review of the literature. Two additional cases of myeloproliferative disorders are described showing as the only chromosome abnormality a loss of the Y chromosome. Comparing these cases with cases reviewed from the literature indicates that a loss of the Y chromosome in Ph1-positive and Ph1-negative CML may cause only a somewhat longer life expectancy following diagnosis. The exact role of the Y chromosome, however, in the initiation or progression of a malignant disorder cannot be stated at this time.


Infant primate larynx: developmental histology. Laryngeal epithelium of monkeys (M. mulatta, M. nemestrina) ranging in age from late fetal to adult was found to undergo the following developmental changes: (1) progressive elaboration of commissural epithelium prenatally, reaching the adult form of pseudostratified columnar ciliated epithelium early in the postnatal period;(2) vocal process epithelium changing from cuboid to stratified squamous tissue during the late prenatal period, and (3) progressive increments in overall epithelial thicknees during development, reaching a maximum in the early postnatal period. Chondrocyte density of the cricoid and thyroid cartilage decreased during the late prenatal period, reaching the adult form at the neonatal stage. The evidence suggests that mechanical or metaplastic stresses do not determine the observed tissue changes.


Non-human primate dental arch form.

Non-human primate dental arch form. Multivariate statistical analysis, based upon a number of dimensions, showed significant contrasts in dental arch form between four primate groups, which was difficult to identify from subjective visual inspection. Furthermore, analysis of dental arch size was shown to differ from dental arch shape, although whether this reflected predominantly genetic or environmental factors, requires further research.


Macroglobulinemia Waldenström and motor neuron syndrome. One patient suffering from macroglobulinemia Waldenström developed a neurological disease which may be a previously unrecognized paramalignant phenomenon in this disorder. The clinical symptoms and signs indicate a motor neuron syndrome and autopsy revealed degeneration of ventral and lateral funicles in the spinal cord, loss of ventral motor neurons, degeneration of ventral nerve roots and muscular atrophy. The rather low incidence of macroglobulinemia and motor neuron disease suggest some causal relationship rather than a sporadic occurrence of two disorders in the same patient.


Changes in the ultrastructure of satellite cells of slow loris in tricresylphosphate poisoning. Toxic reaction of satellite cells from posterior root ganglia of slow loris in TCP poisoning is described. The satellite cells in experimental animals show a marked increase in the rough ER, Golgi complex, microvesicles and filaments. Furthermore there is also an increase in the number of dense bodies and mitochondrial density in these cells. The significance of these changes are discussed and it is concluded that in TCP poisoning not only the neurons but the supporting cells are also affected.


A comparison of the effects of three widely used glutaraldehyde fixatives on cellular volume and structure. A TEM, SEM, Volumetric and Cytochemical Study. The effects of three widely used glutaraldehyde-based fixatives on cellular volume and structure have been studied utilizing TEM, SEM, time-lapse micrography during the fixation procedure, volumetry and demonstration of the lysosomal enzyme acid phosphatase. The cells used were in vitro cultivated human glia and glioma cells and suspensions of isolated rat liver parenchymal cells. The fixatives compared were the following: 2 per cent glutaraldehyde (GA) in 0.1 M Na-cacodylate-HCL buffer (cac) with 0.1 M sucrose (pH 7.2); total osmolality (T) 510 mOsmol; vehicle osmolality (V) 300 mOsm, 2 per cent GA in 0.1 M cac (pH 7.2; T = 410 mOsmol; V = 200 mOsmol) and 1.5 per cent GA in 0.067 M cac with 0.033 M sucrose (pH 7.2; T = 320 mOsmol; V = 170 mOsmol). It was found that the fixative with a vehicle osmolality of 300 mOsmol gave results which were interpreted as ideal while the two fixatives were hypotonic vehicles resulted in changes which were easily demonstrated during volumetry, time-lapse micrography, SEM and cytochemistry. However, the differences observed in the TEM were less obvious and difficult to interpret, the major alternations being changes in the configuration of the ER in the liver cells. In conclusion, our findings show that even small variations in the composition of a glutaraldehyde fixative can result in structural changes which do not correspond to the functional morphology of a living cell. Such changes make correct interpretation of micrographs difficult.


The effects of variations in extracellular magnesium concentration on electrical and mechanical activity in rat portal vein. The effects of various concentrations of extracellular Mg2+ on electrical and mechanical activity of the rat portal vein were studied. The integrated spontaneous contractile activity in the preparation was largest in Mg2+-free solution, decreased to about 50% at 1.2 mM Mg2+ and was almost completely abolished at 10 mM Mg2+. Each spontaneous contraction became smaller whereas contraction frequency was less affected. Sucrose gap recordings showed that the reduced spontaneous mechanical output was associated with decreased electrical activity on increasing [Mg2+]0. Increasing [K+]0 from 6 to 12 mM normalized the spontaneous mechanical activity in 10 mM Mg2+ solution. Local registration of electrical activity with 3 extracellular glass capillary electrodes showed that inactive areas developed at the high Mg2+ concentrations. These findings indicate that Mg2+ exerts a hyperpolarizing action on the smooth muscle cell membrane and, at the highest concentration, interferes with intercellular propagation. [Mg2+]0 in the range of 0-10 mM had no effect on the amplitude of K+ (122 mM) contractures at [Ca2+]0 greater than 0.5 mM. At [Ca2+]0 less than or equal to 0.5 the amplitude diminished with increasing [Mg2+]0. The latter observation indicates that Mg2+ can interfere with the Ca2+-permeability of the depolarized cell membrane. 1 mM EDTA in Na-tris 0 mM Mg2+ and 0 mM Ca2+ seemed to lower intracellular Mg2+ below the minimum concentration needed for contractile activity.


Determination of 58Co-vitamin B12 absorption in pernicious anemia by use of whole-body counting: Reproducibility and control of gut transit time. In 15 patients with pernicious anemia, the fractional retention of 58Co-cyanocobalamin (FRB12) without administration of intrinsic factor (IF) averaged 4.9% (range 0-12.7). With administration of IF, FRB12 averaged 32.7% (range 26.6--42.3) in the patients and 65.6% (range 38.8--84.6) in 16 control subjects. The gut transit time for vitamin B12 was evaluated from the excretion of radiopaque pellets given concomitantly with the 58Co-vitamin B12. The retention of the pellets was positively correlated to that of the non-absorbed 58Co-B12. Control of the gut transit time is recommended at each examination of FRB12 in order to avoid falsely high values due to the retention of non-absorbed 58Co-B12. We found a good reproducibility of FRB12 when determined in fasting subjects, and it is therefore unnecessary to give the patients a B12-free meal prior to the examination. As the FRB12 in all probability is only a little lower than the fractional absorption, the present method is applicalble for the determination of B12 absorption.


Choreoathetosis during phenytoin treatment. A patient with symptomatic epilepsy receiving only phenytoin developed choreoathetosis and orofacial dyskinesias. These movement disorders disappeared when the drug was stopped and reappeared when the patient was challenged. Throughout the period of treatment, concentrations of phenytoin in serum were consistently low within the therapeutic range. Interfering symptoms from the cardiovascular system and the absence of some classic symptoms of phenytoin intoxication (nystagmus and dysarthria) contributed to delay the diagnosis. The patient died in hospital and autopsy of the brain showed rather localized encephalomalacies of corpus striatum. The pathogenic action of phenytoin and the role of preexisting brain lesions are discussed. Phenytoin must be suspected as the cause, when patients on this drug present with uncontrolllable epilepsy or neurological or mental deterioration.


Comparison between serum thyroxine and triiodothyronine estimation and the TRH test in the routine diagnosis of hyperthyroidism. Serum T3 and T4 levels have been determined by a radioimmunoassay technique and the TRH test has been performed in 50 patients in whom hyperthyroidism could not be ruled out by the first clinical examination alone. Each patient was then further evaluated in order to establish the state of the thyroid function. The extent to which the determination of T3 or T4 could replace the TRH test in the routine diagnosis of hyperthyroisism was evaluated. The results showed that 26 of the 50 patients had normal thyroid function and 24 had hyperthyroidism. No patient in the normal groups and all but one in the hyperthyroid group had T3 levels above the upper normal limit (2 S.D.). Two of the patients in the normal group and 19 in the hyperthyroid group had T4 levels above the upper normal limit (2 S.D.). Twenty of the patients in the normal group showed a normal TSH response to TRH (increment is greater than 3.0 micronU/ml); the remaining 6 showed an impaired or absent response. Twenty of the hyperthyroid patients had no response and four had a slightly positive response to TRH. No hyperthyroid patient had a TSH response exceeding 3.0 micronU/ml. It is concluded that the determination of T3 is superior to both the determination of T4 and the TRH test for the laboratory discrimination between eu- and hyperthyroidism.


Divergent changes of serum 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine in patients with acute myocardial infarction. The serum levels of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3, rT3), thyroxine-binding globulin and thyroid-stimulating hormone have been monitored in 13 patients with acute myocardial infarction. The major changes recorded were a transient decrease in T3 and a transient increase in rT3. They reached a nadir and a peak, respectively, within three days. A conceivable explanation for these alterations is that the monodeiodination of T4 is diverted from the activating pathway (T4 to T3) to the inactivating pathway (T4 to rT3).


Urinary excretion of ten plasma proteins in patients with febrile diseases. The 24-hour urinary excretion of albumin, transferrin, haptoglobin, IgG, IgA, IgM, free lambda and kappa light chains from immunoglobulin, lysozyme, and beta2-microglobulin has been investigated in 22 patients with febrile diseases, using an automated immunoprecipitin reaction. The average excretion of the 10 proteins was significantly increased in the patients compared with a control group. In patients with body temperature is greater than or equal to 38.5 degrees C the tubular type of proteinuria was significantly increased compared with those with body temperature is less than 38.5 degrees C. Sequential studies in 10 patients showed that the tubular type of proteinuria occurred in all, whereas the glomerular type was demonstrated in 8. when the fever had subsided, the tubular proteinuria disappeared rapidly i in all patients, while the glomerular proteinuria disappeared in only 4 out of 8. It was shown that tubular proteinuria was caused by fever per se, and it is suggested that glomerular prteinuria might be due to an immue response to antigens, derived from the infectious agents, producing a transient or permanent glomerular injury.


Role of the Hancock "stabilized glutaraldehyde process" bioprosthesis in the management of mitral valve disease. The low mortality of isolated mitral valve (MV) replacement permits attention to be focused on those valve-related factors which affect the quality of life after operation. Comparison of a number of MV prostheses indicates that all perform satisfactorily from the hemodynamic standpoint. An asset of the "stabilized glutaraldehyde process" (SGP) Hancock bioprosthesis (H-B) is the significantly lower incidence of thromboembolism encountered in patients who have not been permanently anticoagulated. While additional time is required before meaningful durability comparisons can be made, the absence of valve failure and the low incidence of tissue dysfunction in H-B over 6 1/2 years is encouraging. Although the ideal device for replacing the MV is not yet available, the Hancock SGP bioprostheses represent the best compromise of available choices.


Severe papillary muscle dysfunction substantiated by atrial pacing during cardiac catheterization. A patient experienced episodic pulmonary edema accompanying nocturnal angina pectoris. The symptoms were provoked at cardiac catheterization by atrial pacing. Simultaneous onset of chest pain, shortness of breath, and sudden appearance of a large V wave in the pulmonary artery wedge pressure contour confirmed acute mitral valve regurgitation. Rapid reversal of these changes after nitroglycerin administration supported "papillary muscle dysfunction" as the explanation for these hemodynamic changes.


Parenteral nutrition of adults with a 900 milliosmolar solution via peripheral veins. The objective of this study was to compare the nutritional value of three parenteral fluids: a conventional solution (400 milliosmoles/liter, containing Na, K, and Cl in 5% glucose); the concentrated hyperalimentation solution of Dudrick (1,800 milliosmoles/liter, containing Na, K, Cl, Mg, Ca, P, and amino acids in 20% glucose); and an experimental solution (900 millisomoles/liter, containing Na, K, Cl, Mg, Ca, P, and amino acids in 6.5% glucose). These three solutions are termed P400, C1,800, and P900, respectively. Preliminary studies showed that when 5 mg of cortisol/liter were added to P900, this fluid could be infused through peripheral veins for as long a time (average 114 hr) as P400 before local reaction necessitated changing the site. When P400 was infused in undernourished subjects without oral intake, balances of N, P, Mg, and Ca/70 kg of body weight per day were strongly negative (-4 g, -0.4 g, -6 mEq, and -0.2 g, respectively), whereas balances of K were about zero and those of Na and Cl were positive. Weight loss occurred. In the same patients, P900 containing 5 mg of cortisol/liter converted balances of N, P, Mg, and K to positive, and stimulated weight gain. Comparison of P900 (containing cortisol) and C1,800 in three emaciated subjects showed that the latter fluid caused a 2 to 4 times greater degree of positive balance in N, P, K, and Mg than the former. Comparison of P900 (containing cortisol) + 670-1700 cal by mouth with C1,800 in four undernourished subjects showed no statistically significant difference between these two programs. by adding 5 mg of cortisol/liter to P900, the fluid can be infused through peripheral veins. P900 is intermediate in nutritional value between P400 and C1,800. P900 without oral supplement prevents negative balance of all elements except Ca. P900 + daily oral intake of 670-1700 cal is nutritionally equivalent to C1,800.


Effect of glucose infusion on the concentration of individual serum free amino acids during sandfly fever in man. After an intravenous glucose load in man, total serum amino acid concentrations are rapidly depressed and remain below baseline values for at least 2 to 3 hr after serum glucose and insulin have returned to preload concentrations. Despite the presence of basal hypoaminoacidemia, a decreased glucose disappearance rate, and hyperinsulinemia in volunteers who were ill with sandfly fever, an intravenous glucose load resulted in a further depression of serum amino acids which was equal to or slightly greater than that observed in the same individuals before exposure to the virus. Although the infectious process may have some effect on insulin-stimulated hepatic disposal of a glucose load, it does not appear to influence the ability on insulin to decrease the rate of release of certain amino acids from skeletal muscle.


Cellular and humoral immunity in non-Hodgkin's lymphoma: correlation of immunodeficiencies with clinicopathologic factors. Immune function was evaluated in 28 non-Hodgkin's lymphoma patients in an attempt to correlate the occurrence of immunodeficiency with the prognostic clinicopathologic factors, lymph-node histology, and clinical stage of disease. Anergy to a battery of recall antigens occurred infrequently (4/28) and only in patients who had Stage IV disease (4/8) (p = less than .004), but did not correlate with lymph-node histology. In contrast to anergy, cellular immunodeficiencies were often detected by lack of response to keyhole limpet hemocyanin immunization in patients regardless of stage. Reductions in at least two of three Ig fractions were found in a third of the patients, with, again, a significantly greater incidence in Stage IV patients (p = less than .005). No significant correlation with histologic type was possible. The response to phytohemagglutinin in vitro was reduced in the patients, but this was of no correlative value.


Abnormal genitalia as a presenting sign in two male infants with hydantoin embryopathy syndrome. Abnormal genitalia was a salient clinical finding in two unrelated male infants with the hydantoin embryopathy syndrome. Both infants also exhibited hypoplastic nails of fingers and toes, hypertelorism, and a flat nasal bridge, and one had severe developmental retardation. We review previously reported cases of the hydantoin embrypathy syndrome and discuss factors possibly affecting the teratogenicity of phenytoin. Male infants with findings such as the patients of this report need to be differentiated from patients with Noonan syndrome and Aarskog syndrome. We suggest that mothers receiving phenytoin who have given birth to one affected infant should be given a different anticonvulsant for future pregnancies.


Trends of brucellosis in Florida. An epidemiologic review. Human brucellosis in Florida is documented for the 47-year period 1928-1975. Of the 936 cases reported in 1930-1975, more than half (505) occurred in the decade 1940-1949. The incidence declined rapidly to an average rate of five cases per year, although there was an increase in 1974 and 1975. The analysis is mainly concerned with the years 1961-1975, since more complete epidemiologic data are available for this period. Cases occurred throughout the year, with the highest incidence being between May and August. White males in the 25-35 and 35-44 deciles were most affected. Of occupations identified between 1963-1975, 44% were related to the livestock-producing industry, 16% to the meat processing industry and 28% to hunters, housewives, students and children. Twelve per cent of the cases did not fall in any of these categories. Cattle were the most probable source of human infection in the livestock industry, and swine were associated with most non-industry cases. In 1963-1975, B. suis was isolated from 10 cases and B. canis from one case; one other isolate was not identified beyond genus. Of the 27 human cases recorded during 1974-1975, 15 (56%) involved swine contact (five livestock industry, four consumers and six hunters), 11 (41%) involved cattle contact (all from the livestock and meat packing industries), and one involved contact (with both cattle and swine (livestock industry). Human cases contracted from swine were scattered statewide, whereas cases associated with cattle only occurred in counties that had )( high densities of cattle and 2) modified-certified ratings in the Brucellosis Eradication Program.


Serologic diagnosis of epidemic typhus fever. Microagglutination (MA), microcomplement-fixation (CF), indirect microimmunofluorescence (micro-IF) and Weil-Felix (WF) tests were compared for sensitivity and specificity in detection of antibodies against Rickettsia prowazekii and for serologic diagnosis of epidemic typhus fever. Paired sera from hospitalized Ethiopian patients suffering from febrile illness were examined. Purified particulate rickettsial antigens used in MA, CF and micro-IF tests were made from infected yolk sacs by differential centrifugation from molar NaCl and from NaCl-sucrose, D20=1.1491, pH 5.5. In sensitivity the tests ranked micro-IF greater than MA greater than CF greater than WF. Use of specific anti-IgG and anti-IgM sera in parallel micro-IF tests made it possible to differentiate cases of recrudescent epidemic typhus (Brill-Zinsser disease) from primary epidemic typhus cases. Antibodies reacting in high titer with R. canada were produced by 86% of patients with rising antibody titers against R. prowazekii.


Population genetics in the province of Ferrara. I. Genetic distances and geographic distances. The ABO and Rh systems of the population in 26 residential units in the province of Ferrara were studied to detect the effect of genetic drift on the differentiation of gene frequencies. Results obtained from principal components analysis and dendrograms were similar. A significant correlation between genetic and geographic distance was found. It was therefore hypothesized that in the area of Ferrara children born to parents originating from different communes were heterozygous at more loci than children born to parents originating from the same commune. It was also thought that it may be possible to use geographic distance between birthplaces of parents as an indicator of hybridity in their children.


Identification of a bactericidal factor (B-lysin) in amnionic fluid at 14 and 40 weeks' gestation. Amnionic fluid (AF) specimens from 40 normal obstetric patients at 14 to 16 weeks' gestation and at 37 to 40 weeks' gestation were found to contain both lysozyme and a bactericidal substance identified as B-lysin. The concentrations of both lysozyme and B-lysin were significantly higher in the AF at 40 weeks' than at 14 weeks' gestation. B-lysin concentration in AF were also found to be significantly higher than in either cord or maternal blood.


The effect of contraceptive steroids on hypothalamic-pituitary function. A study was performed to obtain additional information about the effects of oral contraceptives on pituitary function. A sequential pituitary stimulation test (SST) was used to study normal control women who then received either a combination pill with 50 mug of ethinyl estradiol or an injectable or oral progestin for three weeks, after which the test was repeated. The same test was also performed on five long-term oral contraceptive users. The SST consists of measurement of growth hormone (GH), thyroid-stimulating hormone (TSH), prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) at frequent intervals after stimulation by hypoglycemia, thyrotropin-releasing hormone, and gonadotropin-releasing hormone. GH and TSH release following stimulation were unaffected by the use of contraceptive steroids, while PRL release was increased by both the combination pill and the progestin alone. LH and FSH release was decreased in the three short-term and most of the long-term users of the combination pills but was not decreased in two of the long-term users as well as in those receiving the progestin alone. These results indicate that the combination oral contraceptives have a direct effect upon the pituitary gland, causing an increase in prolactin release and a decrease in gonadotropin release. This effect varies among individuals receiving the same formulation and may be related to the development of syndrome of postpill amenorrhea-galactorrhea.