Immunoglobulins in jejunal mucosa and serum from patients with adult coeliac disease. Immunoglobulin (Ig)-containing cells were quantitated immunohistochemically in biopsy specimens from the proximal jejunal mucosa. The numbers of IgA, IgM, and IgG immunocytes in a defined "mucosal tissue unit" were, on the average, raised 2.4, 4.6, and 6.5 times, respectively, when 13 adult patients with untreated coeliac disease (CD) were compared with 15 patients who had a histologically normal mucosa. The IgA-:IgM-:IgG-cell ratios averaged 66:28:6 in untreated CD and 79:18:2.6 in the controls. Similar quantitative data in 10 patients with treated CD were intermediate. IgD- and IgE-containing cells were rare in all patient groups. Most patients in a heterogeneous malabsorption group showed a jejunal Ig-containing cell population similar to that seen in CD, indicating that the local immunocyte pattern may not be specific for the latter disease. The only significant alteration in serum Ig levels related to CD was a raised concentration of IgA compared with normal. This was consistent with the increased amounts of extracellular IgA revealed in the mucosa. However, there was no indication of a defect in the transport of dimeric IgA and IgM through SC-producing cells, which in the CD mucosa were present in both crypt and surface epithelium.


Immunoglobulins in jejunal mucosa and serum from patients with dermatitis herpetiformis. The quantitative distribution of immunoglobulin-(Ig)-producing cells of the major classes was determined by paired immunohistochemistry in the proximal jejunal mucosa of 29 patients with dermatitis herpetiformis (DH). The specimens were categorized stereomicroscopically in three groups. Compared with controls, the total number of Ig-producing cells in a defined "mucosal tissue unit" was for group I (normal or minor abnormality) found to be raised by a factor of 1.4, but the class ratios remained normal. In group II (major abnormality) the total immunocyte number was raised 2.6 times; IgA, IgM, and IgG cells showed a 2.4-, 3.5-, and 5.1-fold increase, respectively. Group II (intermediate abnormality) fell between the two other groups with regard to changes in the immunocyte population. Altogether the local immunocyte pattern was very similar to that previously found in coeliac disease (CD) specimens of comparable mucosal abnormalities. IgD cells were few, and showed no increase compared with controls. Also IgE cells were few, but were encountered more frequently than in controls. As in CD, staining for extracellular Ig in the lamina propria tended to be more intense than in controls. Normal or increased staining for SC, IgA and IgM in the crypt epithelium indicated a normal external transfer of these components. DH differed from DC in showing no significant rise in the level of serum IgA. Serum IgM was reduced in group III, and IgG was increased in group I.


Plasma follicle-stimulating and luteinizing hormones and the macrosopic characteristics of the ovaries in patients with stein-leventhal syndrome. Response to LH-RH in Stein-Leventhal syndrome. Synthetic luteinizing hormone-releasing hormone (LH-RH) was administered intravenously to 50 women with Stein-Leventhal syndrome and to 15 women with normal menstrual cycle. The patients with Stein-Leventhal syndrome were divided into two groups on the basis of the macroscopic characteristics of the ovaries: group I-with enlarged ovaries--and group II--with normal or diminished ovaries. The basal levels of FSH and LH in group I were greater as compared with those of group II. The maximal increase of both gonadotropins after a LH-RH stimulation was also greater in group I women. On the basis of the results obtained, the elevated basal levels and gonadotropin response to LH-RH test may be used in the differential diagnosis between the two forms of the disease.


Antral gastrin cells and serum gastrin in achlorhydria. Forty-five patients with achlorhydria due to severe atrophic corpus gastritis or gastric atrophy were studied by determination of serum gastrin, histological examination of multiple biopsy from the antrum, and quantitation of gastrin cells revealed by an indirect immunofluorescence technique. In a reference group of 12 persons with normal gastric secretion and without atrophic antral gastritis the mean number of gastrin cells per field of vision was 52 +/- 6.5 (S.E.M.). In a group of achlorhydric patients having normal antral mucosa (n = 24), the serum gastrin levels was 324 +/- 56 pmol/l and the number of gastrin cells was 79.6 +/- 7.5 cells/field of vision. The corresponding values for a group of achlorhydric patients with chronic superficial antral gastritis (n = 11) were 361 +/- 186 pmol/l and 88.0 +/- 14.4 cells/field of vision. In a group of achlorhydric patients with atrophic antral gastritis (n = 10) serum gastrin was 15.0 +/- 3.3 pmol/l, and the number of gastrin cells was 6.2 +/- 3.3 cells/field of vision. Compared to the subjects in the reference group, the number of gastrin cells was significantly higher in the groups of achlorhydric patients with normal or superficially inflamed antral mucosa and significantly lower in achlorhydric patients with atrophic antral gastritis. It is concluded that serum gastrin in general is a good indicator for the presence or absence of antral atrophic gastritis in achlorhydria.


Effects of hydroxyurea pretreatment of donor rats on growth of haematopoietic diffusion chamber colonies in mice. A single dose of hydroxyurea (HU) (400 mg/kg body weight) was injected i.p. into rats. Hydroxyurea, a potent DNA synthesis inhibitor, killed bone marrow cells in the S-phase of the cell cycle. 9-10 h after HU administration, the rat bone marrow contained large numbers of necrotic cells and appeared predominantly lymphoid. Within 24-48 h of HU injection, resumption of normal haematopoiesis was observed. Rat bone marrow, 9-10 h following HU administration, was implanted in peritoneal diffusion chambers (DC) in irradiated mice. The results obtained suggest that pretreatment of donor rats with HU increases the bone marrow content of progenitor cells. The stem cell-enriched marrow was conductive to enhanced growth of DC colonies in irradiated mice.


Constant post-irradiation repopulation rates and linear relationship between cellular blood response and number of transplanted bone marrow cells in inbred mice. Graded doses of syngeneic bone marrow cells were transplanted into lethally irradiated mice. Repopulation curves of peripheral blood granulocytes and platelets were apparently exponential and parallel after doses larger than 5 X 10(5) cells. The blood platelet Td was reduced from 111 h to 53-57 h, and granulocyte Td from 57 to 40 h in transplanted groups. The mean blood cell counts were reproducible enough to be used as a biological assay of the amount of bone marrow cells transplanted. Linear relationship between increment of blood cells up to day 16 and number of bone marrow cells transplanted on day 1 was demonstrated (1,200 granulocytes and 14,300 platelets/mul blood per 10(5) bone marrow cells). The linearity suggested a mean Td less than 22.5 h of proliferating bone marrow cells, and allowed a rough estimation of mouse bone marrow stem cell radiosensitivity (Do 76 rad).


Human leukocyte migration inhibitory factor (LIF). I. Effect of synthetic and naturally occurring esterase and protease inhibitors. The activity of leukocyte migration inhibitory factor (LIF) obtained from Sephadex-G-100-chromatographed supernatants of concanavalin-A-stimulated human lymphocytes was suppressed by two synthetic serine esterase and serine protease inhibitors (di-isopropylfluorophosphate (DFP) and phenylmethylfulfonyl fluoride (PMSF)). LIF activity was also reduced by the naturally occurring protease inhibitors soybean trypsin inhibitor and aprotinin. The observed effect of DFP and PMSF was irreversible, since elimination of the inhibitors by dialysis did not restore LIF activity. The effect of PMSF was dose-, time-, and temperature-dependent, and hydrolytic products of PMSF as well as sodium fluoride were inactive in blocking LIF. These results suggest that LIF may act as a serine esterase or a serine protease, or both of these, and that this putative enzyme is present in an activated form in supernatants from mitogen-stimulated mononuclear cells.


Human leukocyte migration inhibitory factor (LIF). I. Effect of synthetic and naturally occurring esterase and protease inhibitors. The activity of leukocyte migration inhibitory factor (LIF) obtained from Sephadex-G-100-chromatographed supernatants of concanavalin-A-stimulated human lymphocytes was suppressed by two synthetic serine esterase and serine protease inhibitors (di-isopropylfluorophosphate (DEP) and phenylmethylsulfonyl fluoride (PMSF)). LIF activity was also reduced by the naturally occurring protease inhibitors soybean trypsin inhibitor and aprotinin. The observed effect of DFP and PMSF was irreversible, since elimination of the inhibitors by dialysis did not restore LIF activity. The effect of PMSF was dose-, time-, and temperature dependent, and hydrolytic products of PMSF as well as sodium fluoride were inactive in blocking LIF. These results suggest that LIF may act as a serine esterse or a serine protease, or both of these, and that this putative enzyme is present in an activated form in supernatants from mitogen-stimulated mononuclear cells.


Human leukocyte migration inhibitory factor (LIF). II. Partial biochemical characterization of the substrate specificities for this lymphokine. Previously reported experiments suggested that an esterase or a protease, or both, might participate in the expression of human leukocyte migration inhibitory factor (LIF). To clarify this further, a wide variety of simple ester were tested for the ability to protect LIF against inactivation by the serine esterase inhibitor phenylmethylsulfonyl fluoride (PMSF). alpha-N-benzoyl-L-arginine ethylester (BAEE), a typical trypsin substrate, and bis-p-nitrophenyl phosphate (BNPP), a phosphodiester, were the only esters capable of retaining LIF activity in the presence of PMSF. Agents chemically closely related to these esters were inactive. Moreover, the protection afforded by BAEE and BNPP was the king that would be anticipated if the esters and irreversible inhibitor competed for the same site on LIF. Baee and BNPP also protected against inactivation by di-isopropylfluorophosphate (DFP), another irreversible serine esterase inhibitor. In addition, LIF-treated leukocytes partly escaped migration inhibition in the presence of BAEE and BNPP, respectively. These results indicate that human LIF contains a serine residue necessary for lymphokine activity. It is still not proved, however, that LIF as an enzyme is capable of hydrolyzing BAEE and BNPP, although it seems highly possible. The substrate specificities of a putative LIF enzyme are discussed on the basis of the chemical structure of BAEE and BNPP.


The absence of a human thymus lymphocyte antigen (HTLA) on bosophils and mast cells. Basophilic granulocytes and mast cells of different species have been reported to originate from thymocytes and other lymphocytes. These observations were recently confirmed when evidence was given that thymic antigen is present on rabbit basophilic granulocytes. In the study reported here, human leukocytes were tested by the immunofluorescence technique and the immunoelectron-microscopy technique to ascertain whether a human thymus lymphocyte antigen (HTLA) could be detected on their surface. We could demonstrate the presence of HTLA on T lymphocytes but not on basophilic granulocytes, nor on mast cells in Cryostat sections of various tissues.


The effect of levamisole on gingival inflammation in man. The effects of levamisole on gingival inflammation and on cell-mediated immunity were examined in patients with gingivitis and in subjects with clinically healthy gingiva. Treatment with levamisole promoted the development of gingivitis and aggravated the severity of established gingivitis, although the amount of bacterial plaque at the gingival margin was not significantly increased. This effect was short-lasting, as the gingival indices returned almost to base-line values by the end of the fifth month after treatment with levamisole. The development of gingivitis was associated with increased in vitro lymphocyte stimulation by antigens from oral bacteria. The role of cell-mediated immunity in the pathogenesis of gingival inflammation is discussed.


A new rat lymphocyte surface marker: characterization and separation of cells with receptors for Helix pomatia hemagglutinin. Thirty-two percent of neuraminidase-treated DA rat spleen lymphocytes and 48% of lymph node lymphocytes possess receptors for Helix pomatia hemagglutinin (HP). Moreover, these HP-receptor-bearing cells can be separated from B cells by affinity chromatography on HP-Sepharose columns. The virtual absence of immunoglobulin (Ig) receptors and the close correlation with reported T-cell content of these lymphoid tissues suggest that HP-receptor lymphocytes are probably T cells and that HP may provide a convenient marker, for both the identification and the purification of rat T lymphocytes.


The diagnosis of urinary extravasation using gammacamera scintigraphy. Gammacamera scintigraphy studies in three patients with urinary extravasation following renal transplantation are presented. Images were obtained using 131I-orthoiodohippurate. Urinary leakage were detected in each case. The diagnosis were in all three cases confirmed at surgery.


Malacoplakia in a renal transplant. Report of a case studied by light and electron microscopy. A case of malacoplakia in a transplanted patient is reported. Several months after the operation typical lesions with numerous Michaelis-Gutmann bodies were found by biopsies from the urinary bladder and the renal transplant, the latter being ultimately destroyed by the process. Recurrent urinary infections with Escherichia coli might have contributed to the development of the process in combination with an altered macrophage function owing to the immunosuppressive regimen, which was considered mainly responsible for the progressive course of an otherwise benign inflammatory reaction. If malacoplakia occurs in a renal transplant and the renal function deteriorates despite adequate antibiotic therapy, transplantectomy should not be delayed.


Immune deposits in the dermo-epidermal junction in rheumatoid arthritis. Skin biopsies from forty patients with rheumatoid arthritis were studied for presence of immune deposits in the dermo-epidermal junction zone. In about half of these unselected patients with classical and definite rheumatoid arthritis, IgM, complement components and fibrinogen antigenic material were found. A positive correlation is demonstrated between immune deposits and the presence of cryoglobulins in serum. The presence of complement components in the skin deposits was found to be clearly related to the clinical activity of the disease, as judged by Lansbury's index.


Comparative effects of tolfenamic acid and acetylsalicylic acid on human gastric mucosa. A double-blind crossover trial employing gastroscopy, extern gastrocamera and multiple biopsies. A comparative study has been made of the effects of tolfenamic acid (Clotam) and acetylsalicyclic acid on the gastric mucosa in 10 healthy volunteers. The effects were evaluated by means of gastroscopy, photography of the gastric mucosa, and multiple biopsies. The schedule was for a randomized, double-blind crossover trial involving two drug-administered periods of one week's duration separated by an interval of at least 3 weeks. On each day of the drug-administration weeks either tolfenamic acid 600 mg or acetylsalicyclic acid 3 g was administered as three divided doses, taken with meals. Gastroscopy was performed prior to and after each week of drug administration. Subjective side effects were recorded during the therapy periods; haematemesis occurred in 2 volunteers taking acetylsalicyclic acid. The absence of gastritis in each subject during treatment with tolfenamic acid was confirmed both gastroscopically and histologically. In contrast, 6 out of 10 volunteers developed mild superficial acute gastritis after ingestion of acetylsalicyclic acid. The difference in effect between the two treatments on the gastric mucosa was statistically significant(p less than 0.05). The findings of this study are comparable to those of other studies and it is concluded that tolfenamic acid, in the relatively high dosage employed in this trial, is free from any irritant effect on the gastric mucosa.


A comparative study of gastrointestinal bleeding during administration of ketoprofen and naproxen. The gastrointestinal blood losses arising after ketoprofen and naproxen therapy were studied in 12 male volunteers. A 51Cr-technique was used and the study was carried out using a double-blind crossover design. The median daily blood losses were 3.3 and 1.2 ml after ketoprofen and naproxen, respectively. Both preparations caused significantly increased gastrointestinal blood losses compared with preceding control periods, but there was no statistically significant difference between the two preparations.


Synthetic arterial grafts. II. infection complications. A retrospective study of 91 patients with synthetic arterial grafts was made. The investigation showed that infection of synthetic arterial grafts is a serious and life-threatening complication. Of our 14 infected cases, 5 patients were amputated and 4 patients died. The incidence of infection is significantly increased when the anastomosis is performed through a groin incision. In addition the management of patients with infected graft is discussed and two cases are reported.


Repair of stricture and fistula of the antethoracic oesophagogastrostoma using a reversed pectoralis skin pedicle flap. A 68-year-old male patient with oesophageal cancer was treated by oesophageal resection and the antethoracic reconstruction was made by using the ventricle. The oesophagogastrostoma developed a necrosis and later a 5 cm stricture and a gastrocutaneous fistula. Both the stricture and the fistula were treated by plastic surgery using a reversed pectoralis skin pedicle flap and free skin graft.


Natural history of vascular ring with clinical manifestations. A follow-up study of eleven unoperated cases. A clinical follow-up study was performed in 11 unoperated patients with symptoms due to vascular ring. The age at diagnosis was 2-48 months (mean 13 months); 7 of the patients were less than 12 months old. The follow-up time varied between 1 and 22 years (median 7 years). Nine patients were entirely free of symptoms, which they had outgrown in the course of 1-2 years after the diagnosis was made; none of these 9 had symptoms after the age of 4 years. Two patients had symptoms due to either oesophageal compression or to severe associated neuromuscular lesions; the follow-up time was 3 and 1 years, respectively. Our findings lead us to support a conservative attitude regarding surgery, at least if only mild symptoms are present, If the patients can be satisfactorily treated medically, they seem to outgrow their symptoms in early childhood.


[Postoperative stress hemorrhage: ineffective prevention with pepsin inhibitor and deglycyrrhizinized licorice extract. Prospective study]. A double blind controlled study on prophylaxis of postoperative gastrointestinal bleeding from stress lesions was performed. Both tragant sulfate, a pepsin inhibitor, and deglycyrrhizinized liquorice extract proved to be without prophylactic effect.


Recombinational switch for gene expression. Flagellar antigens are specified by two genes, H1 and H2. The expression of these genes is regulated such that only one gene activity, or phase, is expressed at a given time. Molecular cloning techniques were used to isolate the segments of Salmonella DNA which contain these genetic loci. Heteroduplex analyses revealed an anomaly in the cloned fragment, that is, and apparent inversion, which was shown to be adjacent to the H2 gene. A correlation was demonstrated between the phase state of the H2 gene and the sequence of the adjacent segment. We propose that an inversion of this region is the phase-determining event in flagellar gene expression in Salmonella.


Gene cloning and containment properties of plasmid Col E1 and its derivatives. Colicinogenic plasmid E1 (Col E1) and Col E1 derivatives offer advantages as plasmid cloning vehicles with regard to both utility and biological containment. The Col E1 derivative pCR1 does not alter those essential characteristics of the enfeebled Escherichia coli strain x1776 that make this strain particularly useful as a host-vehicle system for recombinant DNA research.


EK2 derivatives of bacteriophage lambda useful in the cloning of DNA from higher organisms: the lambdagtWES system. A derivative of bacteriophage lambda has been modified and tested together with an appropriate host system to meet the criteria of EK2 biologic containment for cloning DNA from higher organisms. In this report certain of the safety features are summarized and some of the tests carried out to confirm the containment properties of the vector are described. The cloning efficiency of this system, together with available gene purification and hybrid screening technology, indicate that it can be used to clone DNA fragments carrying specific, unique mammalian genes.


Screening lambdagt recombinant clones by hybridization to single plaques in situ. A rapid, direct method for screening single plaques of Agt recombinant phage is described. The method allows at least 10(6) clones to be screened per day and simplifies physical containment of recombinants.


Increase in conjugational transmission frequency of nonconjugative plasmids. Addition of Eco RI fragment 6 of the Escherichia coli sex factor F to pSC101 increases the frequency of its transmission by RI-19 and ColVB. Transmission frequencies of pSC101 and two pSC101 chimeras are also increased after the putative transposition of drug resistance element Tn3 from RI-19. These increases may result from addition of an origin of conjugatinal transfer to the plasmids.


Five hundredfold overproduction of DNA ligase after induction of a hybrid lambda lysogen constructed in vitro. A lambda vector that contains the gene for Escherichia coli DNA ligase (lambdagt4-lop-11 lig+) has been modified to achieve overproduction of this enzyme. The third Eco RI site in the lambda chromosome has been altered by mutation, and the left-hand Eco RI fragment has been shortened. The new vector, lambdagt4-lop-11 lig+, forms a stable lysogen which, upon induction, produces a 100-fold increase in DNA ligase activity. Introduction of a phage mutation (S7) that prevents cell lysis results in an even greater increase (500-fold).


Cloning of yeast transfer RNA genes in Escherichia coli. Four thousand Escherichia coli clones containing yeast DNA inserted into the plasmid pBR313 have been isolated. Of these, 175 clones were identified as carrying yeast transfer RNA genes. The initial analysis of the inserted transfer RNA genes via the colony hybridization technique with individual radioactive transfer RNA species is reported. The data indicate that yeast transfer RNA genes are not highly clustered, although some clustering exists. In addition, it was observed that the reiteration number of different transfer RNA genes may vary extensively.


Cloning of cauliflower mosaic virus (CLMV) DNA in Escherichia coli. A plasmid containing cauliflower mosaic virus DNA can be faithfully cloned in Escherichia coli, but proved to be noninfective in test plants.


The effects of Escherichia coli and yeast DNA insertions on the growth of lambda bacteriophage. The effects of Eco RI endonuclease-cleaved Escherichia coli and yeast (Saccharomyces cerevisiae) DNA fragments on the propagation of the lambda bacteriophage vectors containing them were determined on a nonmutanted and a PolA E. coli K12 host. Observable alterations in the growth of hybrids containing yeast DNA insertions were less frequent and less extreme than those seen in hybrids containing E. coli DNA. A lambda-E. coli hybrid was selected after extensive growth on the Pol A (deficient in polymerase I) host which also grew very well on the PolA+ host and may have resulted from some alteration in the hybrid. Hybrids selected on the PolA host gave no evidence for the expression of polymerase I activity. No lambda-yeast hybrid made from the lambdagt vector lacking lambda-specific recombination (red-) had a yield of viable bacteriophage on infection greater than two-thirds that of "wild-type" lambda.


Degradation of DNA by nucleases in intestinal tract of rats. Strains of Escherichia coli K12 have been constructed as safer hosts for use in recombinant DNA research, These strains are unable to survive passage through the intestinal tracts of rats because of a constellation of mutations conferring bile sensitivity and requirements for diaminopimelic acid and thymine. Since death caused by diaminopimelic acid deprivation could release recombinant DNA before DNA is degraded because of thymine starvation, it is important to determine the "survival potential" of the released DNA's. Bacterial and plasmid DNA's extracted from bacterial cells are rapidly degraded when added to low dilutions of rat intestinal contents. This observation, coupled with the stringent requirements necessary for in vitro transformation or transfection, make in vivo transmission of naked recombinant DNA in the rat intestinal tract highly improbable.


Theta-sensitive cell and erythropoiesis: identification of a defect in W/Wv anemic mice. Nonirradiated mice of the W/WV genotype were injected with normal (+/+) bone marrow cells that had been treated with antiserum to Thy 1.2 and complement (C'). Such bone marrow cells had no effect on the number of macroscopic colonies formed in the spleens of these mice, but did not cure the anemia. The addition of +/+ thymocytes to these bone marrow cells restored their ability to cure the anemia in W/WV mice. These data suggest that a theat-sensitive cell is required in the promotion of differentiation of murine hematopoietic stem cells into erythrocytes, and that there is a deficiency of such a cell in the W/WV mouse.


Idiopathic thrombocytopenic purpura in children. ITP in childhood is most often of the acute, self-limited variety, with spontaneous recovery occurring within a matter of days or weeks. In many of these children, acute thrombopenic purpura follows in the wake of a viral infection. While the pathogenesis is not entirely clear, it seem probable that the platelet membrane is altered by virus or by soluble viral antigen-antibody complexes; platelets thus damaged become susceptible to rapid destruction by the RES. Management remains somewhat controversial. While almost all agree that corticosteroid should not be used in all cases of acute childhood purpura, there are still no clear-cut indications for their use, and no real evidence that they are of benefit in reducing the risk of the one rare but serious complication of childhood ITP, namely, intracranial hemorrhage (ICH). In approximately 5-10% of children, ITP ultimately proves to be of the chronic variety, and is in all probability the same condition that is seen in adults. Splenectomy is the treatment of choice, Another small subgroup of children have ITP of the recurrent acute variety; there is some evidence that this entity may also have an autoimmune pathogenesis. Infants born to mothers who have (or have had) ITP often manifest thrombopenia, with or without purpura and other bleeding. While this is generally a benign, self-limited process, requiring no treatment, ICH occurs in a small but significant number of affected infants and probably results from head trauma during delivery.


Joint surgery for rheumatoid arthritis.

Joint surgery for rheumatoid arthritis. The state of the art in the surgery of rheumatoid joint disease is discussed with emphasis on guidelines for choosing the patients and the types of procedures available. Strong-willed, strong-boned, strong-muscled, and well-informed patients are the best candidates. Synovectomy is particularly useful in the minimally erosive stages of the disease when the active synovitis is not suppressed by one or more steroid injections or other modalities of therapy. Arthrodeses and arthroplasties are midstage procedures that are now being supplanted by total joint replacement. This is especially true of the knee, but new prostheses for elbows, shoulders, wrists, and ankles are on the horizon.


Intermittent mandatory ventilation.

Intermittent mandatory ventilation. The introduction of the concept of intermittent mandatory ventilation (IMV) has meant that for the first time weaning is controlled. The abrupt cessation of ventilatory support, even for short periods, as was obligatory before IMV, is no longer necessary. The frequency of positive pressure inflations can be gradually and progressively decreased as indicated, leading to spontaneous ventilation in a planned, controlled program. The ease with which other artificial ventilation technics may be incorporated into this system adds to its usefulness. IMV should be considered whenever ventilatory support is to be discontinued.


Resistance to gentamicin: a growing concern. Gentaminic was introduced in 1969 as a broad-spectrum aminoglycoside effective in vitro against a majority of aerobic gram-negative bacilli. In recent years gentamicin-resistant clinical isolates have become more prevalent. In our laboratory in 1975, 32% of Pseudomonas sp and 44% of indole-negative Proteus sp isolates were resistant to gentamicin. Resistance to tobramycin is also increasing; 24% of Escherichia coli and 28% of indole-negative Proteus sp isolates were found to be tobramycin-resistant. In addition, isolation of previously uncommon gentamicin-resistant species, ie, Proteus rettgeri and other indole-positive Proteus sp, from clinical specimens has increased dramatically in the past five years. This increase in gentamicin and tobramycin-resistant gram-negative bacilli serves as a constant stimulus for the development of new antimicrobial agents.


Prevention of inherited multifactorial diseases. Among the inherited multifactorial diseases are included a number of the common chronic diseases of adults. Assignment of risks within high-risk families, based on both genetic and environmental factors, offers opportunity for prevention of a portion of the present chronic disease burden. The most realistic option for prevention must be assessed for each disease, since this varies from no options to a relatively simple decision to avoid a specific environmental risk factor. Attention to specific options for prevention is an aid to identifying areas of high priority research, such as (1) factors which influence compliance with preventive management, (2) the quality of the physician-patient relationship, (3) environmental monitoring and technics for assessing genetic susceptibility to environmental risks, and (4) education of physicians in the art of chronic disease prevention.


Spinal syphilis: the problem of fluorescent treponemal antibody in the cerebrospinal fluid. Spinal manifestations of syphilis are now uncommon. Three adults with presumptive nontabetic spinal syphilis are presented. This paper should serve as a reminder to physicians that cases of late syphilis continue to occur and may be manifested as obscure spinal syndromes and be misdiagnosed unless the possibility of syphilis is constantly kept in mind. Some of the clinical dilemmas associated with the reactivity of fluorescent treponemal antibody in the cerebrospinal fluid are discussed,


Malacoplakia of the prostate.

Malacoplakia of the prostate. Malacoplakia is a granulomatous disease of unknown cause often associated with a coliform urinary infection. It is occasionally a self-limiting disease with diverse clinical presentations and roentgenographic appearances. The importance of a differential diagnosis which considers malignancy is emphasized. A rare instance of malacoplakia involving prostatic tissue is reported.


Diagnosis of lymphoma from a cholecystectomy specimen: case report and review of the literature. A 31-year-old woman had cholecystectomy for recurrent acute cholecystitis. Pathologic examination of the resected gallbladder revealed unsuspected histiocytic lymphoma. A staging laparotomy seven weeks after cholecystectomy revealed disseminated disease. Lymphomatous involvement of the gallbladder is rarely diagnosed antemortem and indicates disseminated disease until proved otherwise.


Disseminated histoplasmosis in an immunosuppressed patient. A renal transplant recipient was receiving prednisone and azathioprine therapy when he developed fever, cough, and erythema-nodosum-like lesions on the extremities. Disseminated histoplasmosis was diagnosed by skin biopsy. Disseminated histoplasmosis should be considered when a patient under immunosuppressive therapy develops a lesion similar to erythema nodosum or erysipelas with panniculitis.


Hyporeninemic hypoaldosteronism after renal transplantation. Hyperkalemic hyperchloremic metabolic acidosis developed in a patient with posttransplantation renal insufficiency presumably related to allograft rejection. The diagnosis of hyporeninemic hypoaldosteronism was confirmed by finding normal plasma cortisol levels and inappropriately low plasma renin activity and plasma aldosterone concentration in response to stimulating maneuvers.


Nonhealing myelomeningecele in an adult. A case of myelomeningocele in a 20-year-old woman is presented. The partially healed scar continued to produce infected debris despite vigorous local therapy. She died because of eventual local and retroperitoneal invasion of squamous cell carcinoma. The possible benefits of decisive planning are discussed.


Salmonella empyema: a review.

Salmonella empyema: a review. A 35-year-old man developed salmonella pleural empyema during a three-month illness. Cultures of the empyema fluid yielded S enteritidis, serotype typhimurium. Cure was achieved by decortication and obliteration of the pleural empyema space, in combination with chloramphenicol therapy given parenterally. Review of the published reports revealed eight similar instances of salmonella empyema. Manifestations and treatment of this group are reviewed.


The use of the carbon dioxide laser in plastic surgery. For centuries, surgical technics have included sharp metal instruments for incisions and dissections together with time-consuming clamping and tying of vessels with associated blood loss. The CO2 laser presents the first major change in these basic technics. Our brief experience with the Sharplan 791 indicates consistently marked reduced blood loss, less postoperative edema, and less postoperative pain with no increased risk to the patient and no compromise in the end results. Admittedly, much more investigation is necessary to determine its full potential, and perhaps its contraindications. However, it would appear at this time that the proper use of this new modality should be incorporated into our armamentarium of tools for plastic surgical advantages consistent with sound surgical judgment.


Unsterile intermittent catheterization for meningomyelocele. Twenty-five children with meningomyelocele have been managed by clean unsterile intermittent catheterization (UIC). There were 17 satisfactory results, three total failures, and three partial failures under this regimen. Experience, problems, and causes of failure are discussed. UIC offers a definitive form of management for some types of neurogenic bladder.


Myotonic muscular dystrophy in pregnancy. Myotonic muscular dystrophy is an autosomal dominant disease inherited with variable penetrance. With pregnancy, the myotonia and muscle weakness may increase. There is also an increased incidence of abortion, prematurity, fetal death, labor dysfunction, and postpartum hemorrhage. A description of two pregnant patients and a review of the literature illustrate the interaction of the disease and pregnancy.


Glucagon levels in acute pancreatitis.

Glucagon levels in acute pancreatitis. Blood glucagon levels were found to be elevated in patients with acute pancreatitis. The significance of this in the individual patient is obscure, and there was a marked variability from patient to patient.


An evaluation of the effects of some sulphonylureas on platelet function. The effect of the sulphonylureas gliclazide (S 852) and glibenese on platelet function, blood lipid levels and the control of diabetes, was prospectively evaluated in 12 maturity-onset diabetic subjects by means of a double-blind crossover study. Including the pretrial period, platelet aggregation in response to collagen was uniformly lower than in matched normal controls, but neither drug produced any additional effect on platelet function. Control of blood glucose levels was no better than with comparable agents, and no measurable changes occurred in blood lipid levels. The drugs had no significant side-effects and were well tolerated. It is concluded that neither agent offers special advantages over other sulphonylureas, particularly in regard to platelet function.


History of mental health services in South Africa. Part XIV. Psychiatric education. The history of psychiatric education for undergraduates and postgraduates is described and related to the different stages in the development of psychiatry. Nursing education is reviewed from the stage of totally uneducated 'lunatic keeper' to the present highly trained Black and White psychiatric nurses who are capable of taking an active part in the treatment and rehabilitation of the mental patient.


New retirees and the stability of the retirement decision. Examination of the benefit awards data under the social security program may furnish at least partial answers to two questions: What is the estimated number retiring each year? How long do they stay retired? The calculation presented here of the number retiring in 1971 takes into account the fact that the date of the award is not necessarily the actual date of retirement. The difference has been accentuated since Medicare began and individuals have been filing for benefits solely to obtain hospital insurance protection, continuing to earn at a level that precludes receipt of benefits under the earnings test. This study of the data on payable benefits indicates that only a small proportion of retirees lose benefits because of their return to work within 3 years after award.


Rapid antibiotic disk sensitivities of burn eschar and infected wounds. This study was undertaken to develop a more rapid antibiotic sensitivity test of the pathogens in soft tissue infections and burn wound eschar. The proposed rapid antibiotic sensitivity test was performed directly on the clinical specimen rather than on single strains of bacteria isolated from the tissue. By performing the antibiotic sensitivity tests directly on the tissue sample, the physician obtains the test results within seven hours after receiving the specimen rather than 38 to 52 hours later, the time delay encountered with the conventional technique. The modification used did not alter most of the standards advised by the Food and Drug Administration (3), since there was no inclusive change in medium, agar depth or antibiotic sensitivity disk. The changes in the Kirby-Bauer (1) test necessitated by using the clinical specimen did not alter significantly the interpretation of the antibiotic susceptibility. If clinically significant numbers of bacteria, 10(6)-10(9), were present, variations in the inoculum size did not appreciably change the results of the antibiotic susceptibility tests. If the incubation requirement for the standard Kirby-Bauer (1) antibiotic susceptibility test was reduced to seven hours, it also did not significantly limit the accuracy of the test. As expected, the variable most difficult to standardize was the heterogeneous inoculum containing large numbers, 10(7), of different organisms. A zone of inhibition interpreted as sensitive with one organism was occasionally masked by the presence of the confluent growth of an organism in which the zone of inhibition was considered resistant. However, even in this instance, it is possible that mixed culture sensitivities may provide the most valid information in mixed infections, since they more closely simulate the real clinical situation.


Placement of retention sutures.

Placement of retention sutures. A retention suture using the buried technique has been developed. This retention suture encompasses fascia, muscle and subcutaneous tissue and remains extraperitoneally and just below the skin. Since the suture material is not in contact with the skin, complications, such as skin damage, stich abscesses and infection at exit points, are avoided. Severe postoperative pain related to retention sutures is minimized.


An upper extremity skin flap for coverage of thoracic defects. A skin flap based on the medical surface of the upper extremity can be effectively used to close large defects of the chest wall when other lesser procedures prove to be ineffective or inappropriate.


Splenorraphy for the treatment of splenic rupture in infants and children. An 18-month-old black male child who had a successful hepatorraphy and splenorraphy for lacerations of each organ secondary to a six story fall is presented. Splenectomy has been performed in the past 50 years for essentially all splenic trauma. Recent reports have indicated the important role of the spleen in the immunologic defense mechanism, especially in the infant and child. The significance of the loss of the phagocytic activity and antibody response mechanisms iwth an asplenic infant or child are appreciated when one considers the increased morbidity and mortality rates in these asplenic patients. If one further studies the anatomic configuration of the spleen in the infant and child, one may repair a laceration of the spleen successfully in the laboratory as well as in the clinical situation. Although not advocated at this time for general use, a selective approach should be considered for the use of splenorraphy instead of splenectomy in traumatic lacerations of the spleen.


The endothelial damage of pulsatile renal preservation and its relationship to perfusion pressure and colloid osmotic pressure. To evaluate the effects of pulsatile preservation, 34 heterotopic renal autografts with immediate contralateral nephrectomy were divided into four groups with either the pulsatile preservation or cold storage technique. Group I had pulsatile preservation with plasma-albumin perfusate at a mean pressure of 60 mm. Hg and a colloid osmotic pressure (COP) of 20 to 50 cm. H2O. Group II had pusatile preservation with the same plasma-albumin perfusates as in Group I, but at a mean pressure of 30 mm. Hg. Group III had pulsatile preservation with albumin-phosphate buffer solution at a mean pressure of 30 mm. Hg. Group IV used cold storage technique. Group I demonstrated severe endothelial destruction and denuding of basement membrane. The changes were inversely related to COP. None of these kidneys functioned and, following transplantation, had persistent severe tubular damage and plugging of glomerular capillary loops with platelets, fibrinogen, and white cells. In Groups II and III, there were minimal changes, consisting of widening of the endothelial pores and focal endothelial damage. All of these kidneys functioned following reimplantation with minimal ultrastructural alterations. Group IV had no glomerular changes following preservation or following transplantation. All preservation techniques produced proximal tubular damage. There is a definite mechanical lesion associated with pulsatile preservation, which can be minimized by utilizing low perfusion pressures and solutions of high colloid osmotic pressure and which has the potential of producing a picture resembling hyperacute rejection following transplantation.


Venous revascularization of the arm: report of three cases. Three patients with disabling sequelae of venous obstruction in the upper extremity were treated surgically. In one, direct venous repair was used, whereas in the other two, the internal jugular vein was used to bypass the area of obstruction. Restoration of adequate venous return was associated with permanent symptomatic relief.


Yersinia pseudotuberculosis in birds.

Yersinia pseudotuberculosis in birds. 245 Avian strains of Yersinia pseudotuberculosis were isolated over a period of 18 years (1958-1975. Toucans appear to be highly susceptible to pseudotuberculosis. The number of isolates was highest in the colder months (December-March). Serotype 1 was isolated most frequently. There were no essential differences among the five serotypes in sensitivity to chemotherapeutics.


[Epidemiological studies on salmonella in a particular area ("Walcheren Project"). III. The incidence of salmonella in man, insects, gulls as well as foods scrapings from butcher's blocks, effluents of sewage treatment plants and drains from butcher's shops (author's transl)]. In continuation of  previous studies, various materials (meat and meat products, insects, gull droppings, scrapings from butcher's blocks, effluents of sewage treatment plants, drains from butcher's shops and faeces of patients) were examined again at the same time for the presence of Salmonella in a relatively small are (Walcheren) over a period of three months. As was also the case in previous studies, S. typhi murium (27.5 per cent), S. panama (22.2 per cent) and S. brandenburg (9.2 per cent) were the three serotypes most frequently isolated. The three most frequently isolated phage types of S. typhi murium were II 505 (62.1 per cent), II 502 (5.3 per cent) and I 650 (4.2 per cent). The serotypes and phage types were present in nearly all the materials studied which again emphasizes the fact that there are contamination cycles of Salmonella. These studies showed that the route of contamination divides in the butcher's shop. Salmonella ogranisms carried with the meat frome the slaughter-house find their way into the drains on the one hand, and, by meat and meat products, to consumers on the other. Moreover, the high degree of contamination of effluents is not in accordance with the small number of cases of salmonellosis.


[Assessment of bacterial counts in the meat-processing industry. I. A review of the literature (author's transl)]. Frequent examination of large numbers of samples of the surface of carcasses and apparatus is essential to gain a clear insight into the hygiene of the meat-processing line. To make this possible, efforts should be made te reduce the number of sampling sites of each carcass as well as the number of groups of bacteria to the studied, and to save time and material. Methods so far developed to the assessment of bacterial counts are reviewed in the present paper. It is concluded that the spray-pistol method, the Stomacher method, the drop method, the membrane filter method, microcolony counts and the spiral method are particularly eligible for closer examination. The methods referred  to should be tested by the following criteria: (1) simplicity; (2) reliability and reproducibility and (3) saving of time and material.


[Contribution to the aetiology and epidemiology of botulism in broiler chickens (authors transl)]. The second outbreak of botulism in broiler chickens diagnosed in the Netherlands is reported. In this case, the source of botulinum toxin was positively located. Despite the fact that the owner had emphatically assured that all sick and dead broilers had been carefully removed, several carcasses of broilers, almost unrecognizable at first sight, were found to be present in the litter covering the floor, particularly at the rear of the fowl house. The concentration of toxin in the carcasses in the area surrounding this source of infection averaged well over 1,000,000 LD50 per gram of tissue. This is more than sufficient to account for the outbreak of botulism as the oral MLD of the strain of Cl. botulinum type C isolated in previous studied had been found to be well over 4,000,000 LD50 per kg of body weight for chickens, the oral MLD of the strain of Cl. botulinum type C isolated in the second outbreak being found to be 2,000,000 LD50 per kg. of body weight. In discussing the origin of the infection, attention is finally drawn to the possible relationship with the fact that botulism has become increasingly common among waterfowl in the Netherlands since 1970.


[Studies on the problem of a composite anchoring post and core]. The authors conclude from the results of preliminary model experiments that the composite resins Noracryl 100 and Evicrol are suited as materials for stump restoration after the loss of the natural tooth crown in case of primarily shortened root.


A rapid method for the preparation of high potency auto and alloantibody eluates. The present report describes a modified, rapid acid-stromal method for elution of erythrocyte antibodies. With this method, potent crystal clear auto and alloantibody eluates can be produced. The simplicity of the method makes it readily adaptable to the routine serological laboratory or blood bank. In semiquantitative and quantitative studies, we have found that this method compares favorably with other antibody elution methods. With alloantibodies, the rapid acid elution method and the ether method produced the strongest eluates with the ether eluates being slightly more potent than the rapid eluated. By contrast, with autoantibodies the rapid method was clearly superior, producing much stronger IgG erythrocyte coating as judged by the 125I antiglobulin test.


[Adrenal gland cysts. Case reports and potential complications--review of the literature (author's transl)]. Adrenal cysts are rare, mostly harmless, processes, either congenital inborn or acquired by regression, bleeding, infection and tumor. In the case of endocrine dysfunction with arterial hypertension and local expansion with perforation into the retroperitoneal, peritoneal and pleural cavity, purulence, bleeding and vasal obstruction complications are serious. In the differential diagnosis carcinoma of the kidney and the adrenal gland should be excluded.


Immunotherapy of cancer.

Immunotherapy of cancer. Clinical studies have indicated a close relationship between immunological competency and the growth of human cancer. Studies in animal systems have indicated that immunological mechanisms are important in host-tumor existence. A number of agents are in the process of being evaluated for their immunotherapeutic potential in patients with cancer. These include levamisole, bacille Calmette Guérin (BCG) and Corynebacterium parvum. While the precise role of these agents in the treatment of human malignancy remains to be clearly defined, they do appear to be useful as adjuncts to other forms of cancer therapy such as radiation therapy, chemotherapy and surgical operation.


The effect of dioctyl sodium sulphosuccinate on tartrazine azo reduction by intestinal bacteria. 1. Washed whole-cell suspensions of Proteus vulgaris and micro-organisms from rat faeces, reductively cleave the azo bond of the food dye tartrazine under anaerobic conditions. 2. Dioctyl sodium sulphosuccinate, a common faecal softening laxative, when added to incubations in vitro at concentrations greater than 0.005%, increases tartrazine azo reduction in P. vulgaris whole-cell suspensions. 3. By contrast, concentrations of dioctyl sodium sulphosuccinate greater than 0.005% when added to incubations in vitro of rat faecal preparations, resulted in an inhibition of tartrazine azo reduction.


[Influence of centrophenoxine on the effect of cyclophosphamide and chloramphenicol in teratological experiment]. Cyclophosphamide and chloramphenicol underwent a teralogical test in the animal experiment. The prenatal changes in the application of cyclophosphamide reveal the cytostatic remedy as a strong teratogenic remedy, whereas chloramphenicol in the first place has an embryotoxic effect and only a weak teratogenic one. The possibility of an influence on the prenatal changes caused by cyclophosphamide and chloramphenicol was tried with centrophenoxin. Apart from the weight of the foetuses the induced changes remained without influence in cyclophosphamide, whereas in chloramphenicol even in increase of the toxic effect could be observed.


[Morphological studies of experimental lung transplantation. I. Light microscopic and histochemical findings in autotransplants of dog lungs]. Morphological investigations (light microscopy, semithin sections, histochemistry) on autografted lungs showed two changes with mifferent regional distributions. In the upper lobes were found focal areas of slight fibrosis, in the upper and lower lobes degenerative changes especially of the small bronchi and bronchioles with a focal loss of activity of alkaline phosphatase, nonspecific esterase and some dehydrogenase. Possible reasons for these morphological changes are discussed in connection with functional and biochemical results.


[Results and current status of experimental lung transplantation]. The most important findings of autogenous and allogenous lung transplantations in this article. The balance of clinic lung transplantation so far are not encouraging. However they gave new impulses to the animal experiments while they demonstrated that patients with disseminated pathologic pulmonary alterations principally are an another basis for lung transplantation than pulmonary healthy animals. It is tried to derive the next problems of the experimental lung transplantation from the abundance of open questions. Simultaneous it is pointed to that only in ingenious division of labour between many scientic and medical disciplines it is possible to get decisive results with these the risk of further clinical transplantations can be diminished.


Treatment of Gram-negative bacillary meningitis with intrathecal gentamicin. In order to evaluate the effect of intrathecal gentamicin on gram-negative bacillary meningitis, twenty-eight patients were treated with intralumbar or intraventricular gentamicin in combination with systemic gentamicin and with other antibiotics. Sterile cerebrospinal fluid was achieved in 21/22 (95%) episodes of documented gram-negative bacillary meningitis in patients who received more than one day of therapy. Seventy-seven percent of these patients survived their infection. The mean cerebrospinal fluid gentamicin level measured 24 hours after intrathecal administration was 5.9 ug/ml following intralumbar administration and 11.1 ug/ml following intraventricular administration. Toxic side effects due to intrathecal administration of gentamicin were not noted. These findings suggest that both intralumbar and intraventricular administration of gentamicin are safe and efficacious in the treatment of gram-negative bacillary meningitis.


[Severe infections in the newborn after direct kardiototography during delivery (author's transl)]. In a total of 720 CTG-controlled newborns two cases of severe septic general infections were observed; a full-term baby showed an extensive skin of the head phlegmone and meningitis purulenta, both conditions caused by Bacteria coli. A pre-term baby developed suppuration at the site of the CTG-wound and a pulmonary abscess under a general septic condition. The tracheal secretion culture of the patient contained Bacteria pyozyanea. In the case of the full-term child histologic evidence of a chorion infection was established. Both children recovered. Therefore, as we see it, the application of direct cardiotokography makes extensive antiseptic measures and thorough examination of the newborn for infectious complications imperative, a general antibiotic treatment, however, is not considered indicated.


The sequential external counter pulsator: a circulatory assist device. THE THREE GOALS OF CARDIAC ASSISTANCE ARE: (1) To maintain systemic blood flow; (2) To reduce cardiac work and tension development; and (3) To increase oxygen availability to the heart. Toward these ends, various devices and techniques have been developed, including several different types of vascular shunts in combination with or without extracorporeal oxygenation of blood, implantable auxiliary ventricle and augmentation of diastolic pressure by direct counter pulsation of blood through femoral cannulae or intra-aortic balloon.The sequenced counter pulsator is an external cardiac assist device being developed for the therapy of low output syndromes. Investigation in the laboratory has shown that it is capable of increasing cardiac output and diastolic systemic pressure with concomitant reduction in left ventricular end-diastolic pressure. Therefore, it appears to be clinically useful in patients with low cardiac output syndromes.


Drug metabolism under pathological and abnormal physiological states in animals and man. The activity of microsomal drug-metabolizing enzymes is altered by several pathological or abnormal physiological states, such as changes in nutritional status, liver, heart or kidney diseases, hormonal disturbances, pregnancy, tumour-bearing state, adjuvant arthritis, changes in reticuloendothelial system and environmental factors (stress, irradiation, heavy metals). The activities of other metabolic pathways, such as glucuronidation, sulphate conjugation, acetylation and alcohol oxidation are generally affected to lesser extents. Rats are most commonly used in drug metabolism studies, and it is important to know that the activity of most of the microsomal drug-metabolizing enzymes is higher in males than in females through androgen action which is readily impaire drug-metabolizing enzymes in male rats are thus manifested by two mechanisms; one is by impairment of androgen action and the other is by depression of the basic enzymic activity. Therefore, those effects of pathological states, observed only in male rats but not in females, are generally not seen in other species of animals, including man. The effects of starvation, hyperthyroidism, adrenal insufficiency, diabetes and morphine administration are cases where changes in metabolism are due solely to impairment of androgen action. In other pathological cases, those drug-metabolizing enzymes showing sex differences are depressed more markedly in male rats than those showing no clear sex difference. The author therefore recommends the use of female rats in the evaluation of the effects of pathological states on hepatic microsomal drug-metabolizing enzymes. Generally, changes in activity of the hepatic enzymes reflect closely the changes in the rates of drug metabolism in vivo. However, the protein-binding of drugs, hepatic blood flow and renal function are also known to affect the rate of drug metabolism and excretion in vivo, and therefore changes of these factors in pathological states should also be taken into consideration.


[Ourexperiences with clinical methods for localization of urinary tract infections]. On 35 patients with chronical relapsing urinary tact infections with different forms of the clinical course 3 localisation methods for the differentiation of infections of the upper and lower urinary tract, respectively, were evaluated. The results have shown that the bladder washout method was more reliable than the new kidney washout method. The latter method has, however, certain advantages, such as its simplicity and the catheterless accomplishment. The simplest method is the immunofluorescence investigation of the urinary sediment on the germs coated with antibodies. This method, however, still contains several unclear sources of error.


[Aplasia of the pancreas with diabetes mellitus, aplasia of the intrahepatic bile ducts, and additional malformations in a small for date baby (author's transl)]. A report is given on a 4 days old female small for date baby with a birth weight of 1210 g and a length of 37 cm. Beside other malformations (common arterial trunk,ventricular septal defect) it revealed an aplasia of the excretory pancreas and of Langerhan's islets with diabetes mellitus as well as intrahepatic aplasia of bile ducts. The malformations of the pancreas and the liver are discussed. Special emphasis is laid on the rarity of these findings.


[The multifocal progressive leukoencephalopathy--a papova-virus-encephalitis (author's transl)]. Two cases of multifocal progressive leukoencephalopathy are reported. A 62 years old patient suffering from lymphosarcomatosis for more than 5 years developed neurological symptoms and died 7 weeks after their onset. In a 44 years old patient a kidney transplantation was performed. 6 months after that operation he developed a disorder of the central nervous system and died 3 weeks later. Post-mortem examinations revealed the characteristic morphological findings of multifocal leukoencephalopathy in both the cases. Electron microscopic examination of the brain tissue obtained at autopsy demonstrated virions in paracristalline arrangement within the nuclei of oligodendrocytes. These findings are identical with those reported in literature, that were regarded as papova-viruses. Therefore, it is suggested to name the disease a papova-virus-encephalitis.


[Induction of tumours by different endogenously formed N-nitroso-ureas in the hooded rat (author's transl)]. By means of application of methyl-, ethyl-, n-propyl-, iso-propyl- and n-butylurea together with sodium nitrite the formation of corresponding carcinogenic N-nitroso compounds is demonstrated. The transplacental action of endogenously formed ethylnitrosourea led to a characteristic spectrum of tumours in the offspring comprising mainly neurogenic neoplasms of the brain and Nn. trigemini. The tumour incidence is especially high after application of precursors (ethylurea and nitrite) with the food. In postnatal experiments with methylurea and nitrite, there were induced mostly neurogenic tumours and reticulum cell sarcomas of the paracoecal region. A similar spectrum of tumours was found after postnatal application of iso-propylurea and nitrite by gastric tube. After a single dose of iso-propylurea and nitrite at day 21 of pregnancy there seems to be a slight carcinogenic effect in a small group of animals. The application of n-propylurea and n-butylurea, resp., together with nitrite led mainly to reticulum cell sarcomas of the paracoecal region after formation of corresponding alkylnitrosoureas. The spectrum of tumours is compared with that after the action of complete carcinogen and with the results obtained by other authors.


[Some remarks on recent trends in pathology (author's transl)]. The present situation of pathology is analysed. Concerning the German Democratic Republic the situation is characterized by a consequent separation of the pathology into the special branches of pathomorphology, pathophysiology, and pathobiochemistry.


[Surgery and therapeutic pathomorphosis (author's transl)]. Th. Billroth was the symbol of a biological awakening out of the only technically stamped surgery of the 19. century. The second half of our century faces a completely new problem: the pitfalls of medical progress.


[The Billroth I-reesection and its pitfalls (author's transl)]. Provided the indication is correct, the Billroth I-method yields very good results. The surgical procedure is presented in detail, also its early and late complications and their treatment. The author performed 552 end-to-and end-to-side gastroduodenal anastomoses with a lethality rate of 0,9%.


[Characterization of staphylococci in microtiter-plates (author's transl)]. The conventional methods for the demonstration of coagulase, clumping-factor, fermentation of mannitol, protein A, alpha-, beta-, and delta-hemolysins and acid phosphatase were adapted to a microtitersystem (MTS). This led to a considerable saving in working-time and reagents. The biochemical reactions could be distinctly evaluated in the MTS (fig. 1). In all qualitative determinations there was complete agreement between the results obtained by MTS and the conventional procedures. In the quantitative endpoints there were only minor deviations (fig. 2,3,4). Thus, the MTS appeared to be a suitable procedure for the characterization of pathogenic staphylococci at a large scale.


Transfer of invertase production from a wild strain of Escherichia coli. A wild type strain of E. coli which produced an invertase capable of hydrolysing sucrose and raffinose transmitted this ability at high frequency to a recipient strain. E. coli C. The ability to ferment both sucrose and raffinose was lost both in the wild type parent and recombinant strains by treatment with ethidium bromide.


Production of precipitating antibodies in chickens infected with Salmonella gallinarum. Vaccination of 10 days old chicken with a live relatively avirulent S. gallinarum induced antibodies against the main antigens of the pathogen, namely, its proteins. Precipitations in agar gel were obtained against the free proteins and the protein conjugated in the somatic antigen of S. gallinarum and against antigens from the related S. enteritidis. Antipolysaccharide antibodies were induced in small quantities which were however sufficient to allow their identification with the agar-gel-diffusion technique.


Rapid surface colony counts determination with three new miniaturised techniques. Three different miniaturised methods for the rapid surface viable counting are described. The methods were tried in parallel to seven different existing methods (Table 1) for viable counts and were found to be easier, quicker and insome cases more accurate. The techniques require about 10% of the material and time needed for conventional spread-plates method and the results were in no way inferior to that (Table 1 and 2). Mini agar discs were cut aseptically with an especially designed stainless steel agar disc cutter (25 mm internal and 28 mm external diameter, Fig. 1b) or with a test tube of similar diameter. The area of the resulted mini-agar-disc of 25 mm diameter was kept such (about 1/10th of the normal plate) that the ratio of the colony-bearing area to the inoculm remained the same as on big plates in spread-plate-method (Table 2). In normal Petri dishes (about 90 mm diameter) up to seven mini agar discs were possible to cut. Each small agar disc was seperated from the other mini-disc by a distance of at least 6 mm (Fig. 1a). The empty place around the disc was still enlarged during over drying of the plates and during incubation. This created complete isolation from the neighbouring disc. For micro-determination of surface viable counts 10 micronl from each dilution was delivered on a well-dired mini-disc with a piston micropipette. The inoculm was immediately spread on the whole mini-disc with a specially designed flame sterilizable platinum-Mini-spreader (Fig. 2a). No spinning of the plate was needed. Alternatively the dropping pipette and spreader was replaced by a calibrated platinum wire Loop-spreader (Fig. 2b). A loop of 3 mm internal diameter made from a platinum-iridium wire of 0.75 mm thickness proved most useful and carried a drop of 10 micronl. Differences especially in surface tension of various diluting fluids did not influence to drop of this size and no recalibration was needed for water and nutrient broth. The loop was further shaped to Loop-spreader form. From each bacterial suspension 10 micronl were carried and spread on each mini-disc. The method is useful for pathogenic organisms as the loop can readily be flame sterilized. For routine purposes where only approximate numbers of bacteria need to be known a still rapid semiquantitative method was deviced making use of a calibrated stainless steel Stamping-disc (Fig. 2c). A disc of 25mm diameter and 1 mm thickness delivered approximateyl 10 microlitres of supensions and was found to be most useful to stamp seven dilutions on a single plate. In collections and bacteriology laboratories where by conventional methods large number of plates are to be plated and counted the presented techniques could prove most convenient, rapid and economical.


Comparison of the proteolytic specificities of bovine and porcine pepsin A. Bovine pepsin A inactivates pancreatic ribonuclease through a limited proteolysis the same way as does porcine pepsin A. The specific activity is lower and more dependent on the ionic strength. The proteolytic specificity of bovine pepsin A has been investigated with B-chain of oxidized porcine insulin as the substrate. The specificity resembles qualitatively that of porcine pepsin but with quantitative differences.


[History of lumbar sympathectomy from its origin to the present]. The author first recalls the origins of the words "sympathetic" and "neurovegetative system" and then outlines the beginnings of surgery on the autonomic nervous system in general. This started with the section of the rami communicantes introduced by the Australians Royle and Hunter in surgery of the muscle tone. Then nearly at the same time in 1924. Adson in USA and J. Diez in Argentina resected the lumbar sympathetic chains; the latter mainly for treatment of thromboangeitis obliterans. From 1924 on, lumbar sympathectomy met with rapid success as shown at the Cairo Congress of 1935. Physiologic and pathologic effects of lumbar sympathectomy are analysed and the usual techniques are reviewed. The author then lists the specific postoperative complications, including the pain symdroms and the functional sexual disorders in males. Finally the principal indications where lumbar sympathectomy proved useful are named. Chronic obliterative arteriopathies are the first. For these lumbar sympathectomy still holds a palliative, supportive or absolute role. A scheme illustrates its beneficial actions.


Influence of LH/FSH releasing hormone (LRH) on the basal secretion of gonadotrophins in relation to plasma levels of oestradiol, progesterone and prolactin during the post-partum period in lactating and in non-lactating women. The pituitary responsiveness to LH/FSH releasing hormone (LRH) was studied in the puerperium in lactating and in non-lactating women. The response of both groups of patients to 25 mug LRH iv was tested 8-10 days, 15-17 days, and 29-32 days after a normal delivery at full term. The basal levels of FSH were low during the first 10 days after delivery. A rise was then observed, and about 4 weeks after delivery levels above or in the upper normal range of a normal follicular phase were recorded. The levels were significantly higher in the lactating group. When compared with the normal follicular phase, the relative increase in FSH basal levels was higher than the increase in LH basal levels in both groups of patients. The period of non-responsiveness of the pituitary to LRH was found to be of equal length in the two groups. In both groups the FSH response returned more rapidly than the LH response. About 2 weeks after delivery a reverse pattern of gonadotrophin response to LRH was seen with a FSH response that was greater than the LH response compared with what is generally observed in the various phases of the menstrual cycle in eumenorrhoeic women. This pattern was more pronounced in the lactating group about 4 weeks after delivery. Oestradiol levels were low and roughly equal on the three test occasions in each group, but in the non-lactating group there was a tendency to higher concentrations. Prolactin levels were highest about one week after delivery and then showed a tendency to decrease, and this was more pronounced in the non-lactating group. Progesterone levels were invariably low in both groups.


Hypogonadism, galactorrhoea and hyper-prolactinaemia: Evaluation of pituitary gonadotrophins reserve before and under bromocriptine. Twenty patients with hypogonadism (19 women with amenorrhoea and 1 man with impotence and infertility), galactorrhoea and hyper-prolactinaemia (range: 36 to 344 ng/ml) were studied. The radiological study of the sella turcica, including in all cases hypocycloidal tomograms, allowed classification of the patients into 3 groups: group I (n = 4) had a grossly enlarged sella turcica, group II (n = 12) had localized alterations indicating the probable existence of a prolactin-secreting microadenoma ("microdeformation") while group III patients presented no radiological abnormality. Before treatment, all the patients were submitted to a complete evaluation of the function of their anterior pituitary, including the LH and FSH responses to iv administration of Gn-RH. All the group I patients had low basal LH levels and a blunted response to Gn-RH. The basal LH and in response to Gn-RH were normal in most of the group II patients and in all of the group III patients. An exaggerated FSH response to Gn-RH was observed in 6/12 patients with microdeformation (group II) but not in groups I and III patients. A low LH and a blunted LH response to Gn-RH is highly suggestive of the existence of a pituitary prolactin-secreting adenoma in case of amenorrhoea and hyper-prolactinaemia patients; a normal response does not however rule out such a diagnosis. The reasons for a exaggerated FSH response to Gn-RH in patients with suspected prolactin-secreting microadenoma remain to be investigated though this pattern can also occur in other cases of amenorrhoea. Hence the Gn-RH test might contribute to the assessment of the hypothalamo-pituitary axis of patients with hyper-prolactinaemia. Six patients treated for 4 months with bromocriptine (CB-154) were submitted to re-evaluation of their pituitary gonadotrophins reserve. All the women experienced restoration of menses with 39 days of treatment and the male patient regained potency. It was observed that bromocriptine treatment and subsequent normalized prolactin levels in the 4 group II women tested were associated with normalization of their previously exaggerated FSH response to Gn-RH; LH responses were also diminished in these cases. These data are compatible with the hypothesis that hyper-prolactinaemia per se could interfere with the endogenous secretion of Gn-RH at the hypothalamic level. In one patient with grossly enlarged sella turcica and a previous lack of an LH and FSH response to Gn-RH, bromocriptine treatment restored a normal gonadotrophins response, confirming that, in this case, the alteration of this response was indeed due to a prolonged lack of endogenous Gn-RH secretion.


Glucocorticoid and mineralocorticoid actions on gastric secretion in man. The effects of a 6-day course of treatment with a glucocorticoid (prednisolone, 1 g per day i.v.), a mineralocorticoid (9-alpha-fluorohydrocortisone, 0.3 mg per day orraly), or both the drugs on gastric secretion of acid, protein, pepsin, and N-acetylneuraminic acid (NANA) containing glycoproteins were investigated in 22 volunteers. None of the treatments produced any statistically significant changes in gastric secretion of aggressive factors, acid and pepsin. However, the output of protective NANA bound to glycoproteins was found to be decreased following prednisolone. The prednisolone effect was not prevented by 9-alpha-fluorhydrocortisone given concomitantly. Gastroduodenoscopy did not reveal any lesions attributable to drug adminstration.


Human hepatic blood flow and its relation to systemic circulation during intravenous infusion of lidocaine. Twelve healthy young volunteers were studied before and during intravenous administration of lidocaine at a dose rate of 2 or 4 mg/min. Five additional volunteers, who did not receive lidocaine solution but were given the same amount of physiological saline, were studied in the same manner. Heart rate, cardiac output, mean arterial blood pressure, mean right atrial blood pressure, estimated hepatic blood flow and plasma concentration of lidocaine were measured repeatedly. The results showed an increase in heart rate, cardiac output and mean arterial blood pressure, the latter two variables in relation to the plasma concentration of lidocaine. The estimated hepatic blood flow increased, partly as a result of the reduction of splanchnic vascular resistance and partly due to the stimulation of cardiac output. The decrease in splanchnic vascular resistance was proportional to the plasma concentration of lidocaine.


Observations on physiological and psychological functions of the ventral oral internal nucleus of the human thalamus. Eight patients underwent VOI thalamotomy for spasmodic torticollis or choreoathetosis. The clinical results were disappointing: at follow-up examination 8 months postoperatively, on average, none of the seven patients with torticollis regarded the effect as good. In two there was some long-lasting improvement, but in five the results was nil. One patient with choreoathetosis did not benefit from surgery. Side-effects were frequent but not serious; they included excessive sleepiness, drowsiness, weight increase, deterioration of memory and loss of general activity. Electrical stimulation of the VOI nucleus caused subjective sensations in the neck and shoulder muscles without movements of the head, and autonomic or emotional reactions. An evoked scalp response was recorded in contralateral frontal area 8. As shown by psychological tests, in visuospatial performances there is a preoperative defect, which seems to be specific to spasmodic torticollis. After left VOI thalamotomy both receptive and expressive verbal efficiency were impaired. Visual perception and memory were almost unaffected by VOI thalamotomy.


[T and B lymphocytes in peripheral blood of subjects receiving atropine]. Using the rosette test E and EAC and determining presence of immunoglobulins on the surface of cells T and B lymphocyte counts were calculated in peripheral blood of 10 healthy subjects receiving atropine for some days. Parallely the activity of T cells was evaluated on the basis of blastic transformation degree after PHA stimulation. No differences were observed in the counts of T and B lymphocytes in peripheral blood before and during atropine administration. T lymphocytes showed, however, functional defects manifested with impairment of PHA-stimulated transformation.


An ultrastructure study on antibody production of the lymph nodes of rats with special reference to the role of germinal centers. Antibody-containing cells in lymph nodes, expecially in germinal centers, and in thoracic duct of rats sensitized by injection of horseradish peroxidase were studied with the immunoperoxidase method. In the primary response the large germinal center cells began to produce antibody on the 9th day and predominated thereafter in germinal centers ,added by intercellular antibody deposition in its late stage. The "ordinary" medium-sized germinal center cells were a minor component. In the secondary response, the intracellular antibody positivity disappeared immediately after the antigenic rechallenge but reappeared from 6 hours later in the large germinal center cells which further transformed from 48 to 72 hours into the "specifically differentiated" medium-sized germinal center cells that disappeared by 96 hours after the secondary injection to enter the thoracic duct. Antibody-containing cells outside the germinal centers appeared 5 to 6 days after the primary injection and were mainly comprised of plasmocytic cell series which was classified into interfollicular large cells, proplasmocytes and plasmocytes. Some results conflicting with the cytological identity of both cell series were presented.


The endocrine pancreas in early alloxan diabetes. Including study of the alloxan inhibitory effect of feeding and some hexoses. Starved animals were sensitive to alloxan, whereas a more or less inhibitory effect towards alloxan was observed in fed animals, and in starved animals pretreated with glucose, mannose or fructose, but not in those pretreated with galactose. The islets of starved controls possessed larger B-cell mitochondria than those of fed ones. The earliest B-cell changes in the alloxan-treated animals were localized to the mitochondria which showed swelling, and disruption of inner and occasionally outer membranes. Later, many mitochondria were disintegrated, and the endoplasmic reticulum and Golgi complex disorganized. The secretory granules were preserved, although sometimes with atypical configuration, in degenerating but non-necrotic B-cells, suggesting that insulin stored in granules is not released until the cells are necrotic. Finally, frank necrosis was seen in some B-cells, whereas others were unaffected. The Ca2+-precipitation studied by pyroantimonate technique and x-ray analysis differed in the B-cells of the alloxan-treated animals from that in the controls; the former animals exhibited no or only sparse precipitation in mitochondria and secretory granules, but a rich precipitation in the cytoplasmic ground substance, whereas the precipitation in the controls mainly was localized to mitochondria and secretory granules. The primary site of alloxan action in the B-cells is believed to be localized to the mitochondria.


Comparative bioavailability of oral dosage forms of oxazepam--correlation with in vitro dissolution rate. Four oxazepam tablet preparations and a suspension of micronized oxazepam in water were given to healthy, fasting volunteers in a comparative bioavailability study using a partial cross-over design. Urinary recovery (0-72 hours) was used as a measure of extent of absorption. Peak serum concentration was used as a measure of rate of absorption. The three dosage forms having the highest dissolution rate in vitro were absorbed to the same extent, while slower dissolving tablets were not as fully absorbed. Peak serum concentration correlated linearly with in vitro dissolution rate. Single oral doses of oxazepam tablets containing 10, 15 and 25 mg showed equal rates and extents of absorption and produced serum concentrations linearly correlated with dose.


S-tryptophan concentrations after intestinal bypass in extreme obesity. Treatment of extreme obesity with jejunoileostomy was followed by a decreased level of S-tryptophan; permanently low concentrations were recorded postoperatively in 29 out of 52 patients. Patients in the low tryptophan group had a higher rate of weight loss and a hgiehr incidecnce of electrolyte disturbances and signs of liver injury. Symptoms of depression and anxiety were slightly more common in patients with low S-tryptophan. The influence of a decreased S-albumin and a deranged amino acid pattern on the non-protein-bound fraction of S-tryptophan needs further investigation. Serum levels of tryptophan rose significantly after rwo weeks' oral supplementation with 1.2 g L-tryptophan daily; this dosage was insufficient to normalize a low S-tryptophan level in patients who have undergone jejunoileostomy.


The clinical significance of retinitis pigmentosa without pigment: a computer assisted analysis. Sixty-eight consecutive patients with retinitis pigmentosa were studied to determine the frequency of the non-pigmented form of the disease. There was an overall incidence of 22%. Fifty percent of all cases had no characteristic pigmentation, if the duration of night vision difficulty was three years or less. The study lends statistical support to the concept that the non-pigmented form of retinitis pigmentosa is frequently an early stage of the disease and not an unusual or atypical variant. Patient without the pigmentary changes characteristic of the disorder also showed less functional impairment: the ERG b-wave was more apt to be recordable, although impaired; and the rod threshold, as determined by dark adaptation measurement, was less elevated. The clinician should suspect retinitis pigmentosa, even in the absence of pigmentary changes, if there is a family history of the disorder, night blindness, peripheral field loss, and an impaired or non-recordable electroretinographic response.


Immunohistochemical localization of gonadotropin-releasing hormone (GnRH) in the fetal and early postnatal mouse brain. The objectives were to (a) determine the age in development when GnRH is first detectable in the brain and (b) observe the distribution of GnRH throughout the fetal and early postnatal period. GnRH was localized immunohistochemically in fetal (15, 16, 17 and 19 days of gestation) and early postnatal (1- and 7-day-old) mice with the peroxidase-antiperoxidase (PAP) method of Sternberger. In the organum vasculosum of the lamina terminalis (OVLT) and in the median eminence of the fetus, GnRH was first detected at 17 days of gestation. In the OVLT, GnRH was found ventral to the preoptic recess of the third ventricle near the ventral surface of the brain. In addition, GnRH was located adjacent to the superficial portal capillaries near the surface of the median eminence. At 19 days of gestation, the distribution of GnRH was similar to that observed at 17 days and there was a marked increase in amount. In the newborn mouse, GnRH was undetectable in the OVLT and its content in the median eminence was decreased as compared to that observed in the fetus. By the seventh postnatal day, a considerable accumulation of GnRH had occurred in the OVLT and median eminence. In the OVLT, it was associated with capillaries ventral to the preoptic recess, and its distribution in the median eminence was similar to that in the adult mouse. In both the OVLT and median eminence of the fetal and early postnatal mouse GnRH appeared to be stored in axons and axon endings, but was not detectable in nerve cell bodies or ependymal cells. These observations suggest that the potential for neuroendocrine control of gonadotropin secretion exists in the fetal mouse early as 17 days of gestation.


An immunocytochemical study of human pituitary mammotropes from fetal life to old age. The objectives were to (a) describe the cytology and distribution of mammotropes in the human pituitary gland, (b) determine whether the mammotrope is a distinctive secretory cell type and (c) ascertain when it first appears in the fetal hypophysis. Identification of mammotropes was based primarily on the Sternberger peroxidase-antiperoxidase immunocytochemical method used with an antiserum to human prolactin. Hypophyses from 25 male and 6 female adults, and 21 fetuses ranging in gestational age from 6 to 23 weeks were studied. In the adult two morphological forms of mammotropes were observed. Mammotrope I possessed a small perikaryon that commonly was located centrally in parenchymal cell cords. From the perikaryon long cytoplasmic processes extended toward neighboring capillaries. Mammotrope I reached its highest incidence in the posterolateral zones of the pars distalis. Mammotrope II possessed a larger perikaryon with short processes; cells of this form were fewer and occurred chiefly in the anteromedian zone. Mammotropes with intermediate morphological features that prevented classification into categories I or II were common in some hypophyses. Both forms of mammotropes were present prepuberally (one 6-week and one 9-year-old male) and in adult males and females. Mammotropes were only slightly more prominent in females than males. Regression of mammotropes was evident in old age. Mammotropes were distinctly different from somatotropes, corticotropes, gonadotropes and thyrotropes. In the fetal hypophysis mammotropes appeared first at 14 weeks of gestational age and remaind few through 16.5 weeks. Their number increased greatly at 23 weeks.


A contribution to our knowledge of ginseng. The Chinese people discovered ginseng and used it as a revitalizing agent since time immemorial. They are still the world's major consumers of this plant drug. The commercial product of ginseng comes from two species of the genus Panax in the family Araliaceae. These species are P. ginseng C. A. Meyer which is the source plant of the Chinese, Korean and Japanese brands of ginseng, and P. quinquefolius L., which is the source of American ginseng. Phytogeographically, ginseng demonstrates the classical bicentric pattern of plant distribution, with closely related species in eastern Asia and in eastern North America. Ecologically, ginseng is an undergrowth of hardwood mixed deciduous forest. It prefers the northern or the northeastern slope of a hill. Species of the genus Tilia are good indicators of the proper environmental condition for the growth of ginseng. Morphologically, ginseng is a perennial herb with fleshy root, a single annual stem bearing a whorl of palmately compound leaves, and a terminal simple umbel of small 5-merous flowers. The flowers are soon followed by pea-sized fruits developed from inferior ovaries. The fruits are red when ripe. Ginseng is propagated by seed. The commercial products of ginseng consist primarily of roots 2-20 years old. Within this age range, the older the root the higher the market value, provided they are grown in proper conditions. The methods of curing the roots change the color and shape of the products. Chinese ginseng is prepared from roots bleached, boiled, steamed, or sugared in curing. The cultural background for the uses of ginseng by the Chinese people is explained. Ginseng may be used alone in the form of tea, powder, or as a masticatory. It is also used in combination with other drugs of animal, mineral, or plant origin. Forty-two recipes are selected from Pen-ts'oa kang-mu and translated into English for the first time to show the various ways by which ginseng is used in traditional Chinese medicine. A systematic summary of the companion plant drugs of ginseng is presented in the form of a table, showing the distribution of the species in the plant kingdom. The scientific names of the species are given in full.


An unsuccessful attempt to treat hypertension with acupuncture. The effectiveness of 5 sets of acupuncture loci in decreasing systemic blood pressure was compared with chlorthalidone and propranolol in patients with essential hypertension. No statistically significant acute or long-term changes in plasma catecholamines, renin activity, or blood pressure and pulse rate were observed as a result of acupuncture treatment. The decrease in blood pressure was significantly less than that observed with propranolol, but not significantly less than that produced by chlorthalidone. Because of the poor patient acceptance of acupuncture and in the absence of a beneficial response, we feel acupuncture as employed in this study is of limited value in the management of patients with essential hypertension.


Correlation of the serial-dilution protamine sulfate test with models of "hypercoagulability" and thrombosis in dogs. In a dog model, combinations of venous-injury thrombosis, homologous serum-induced "hypercoagulability," and fibrinolytic blockade were evaluated to determine the factors involved in the generation of a positive serial-dilution protamine sulfate test. Stasis and operative procedures did not produce a positive test. Small local thrombi induced by electrical current produced a positive test that tended to persist only during the initial formation and propagation of the thrombus, and was blocked by pretreatment with epsilon-aminocaproic acid, suggesting in this model that the test was detecting mainly early fibrin degradation products. Homologous serum infusion without venous-injury thrombosis also produced positive serial-dilution protamine sulfate test results that could not be blocked with epsilon-aminocaproic acid suggesting here that the serial-dilution protamine sulfate test was detecting mainly soluble complexes of fibrin monomer rather than early fibrin degradation products. The serial-dilution protamine sulfate test is therefore capable of detecting both small local thrombi and serum-induced "hypercoagulability" without thrombosis in the dog model.


A comparative study of technics for the detection of antibodies to native deoxyribonucleic acid. Antibodies to native DNA have been assessed by three separate radioimmunoassay methods: the Millipore filter technic, the Farr ammonium sulfate precipitation test, and a commercially available kit method. Although each method was found to be reliably reproducible, the different units by which results are expressed made comparison difficult because of the technical variations inherent in each test. The correlation between tests was, however, high. To allow for interlaboratory standardization, it is suggested that the assay method used be clearly specified. Results are best expressed in terms of mg of DNA bound per deciliter of test serum. It appears that the centrally standardized radioimmunoassay kit is the most convenient method by which these antibodies can be measured in routine laboratories.


Infection in infants and children.

Infection in infants and children. Infection with Listeria monocytogenes is demonstrated over a 141/2 year period in 24 newborns, three infants 1 to 2 months of age, and two children. Comparison of the 22 cases of Listeria meningitis in newborns with 118 cases of neonatal meningitis due to other bacteria indicates a later onset of symptoms in cases of Listeria meningitis with a more favorable outcome than with most other agents. Treatment with ampicillin sodium appears effective. Monocytic cell increases in peripheral blood or CSF may be helpful in suspecting this diagnosis. The cases of Listeria meningitis in the older children were unusual. In one child it occurred as a concomitant infection with Staphylococcus epidermidis of a ventricular shunt. In the second case in an otherwise healthy child the acquisition of the bacteria from gerbils was suggested, but could not be confirmed.


Neonatal listeriosis.

Neonatal listeriosis. Five cases of neonatal listeriosis were diagnosed and treated in a 13-month period. Maternal fever and "greenish discoloration" or meconium staining of amniotic fluid complicated all deliveries. Amniotic membranes were intact until artificial rupture shortly before delivery. One infant, with the "granulomatous" form of the disease, died. Four infants required mechanical ventilation. Two survivors with pneumonia, who required mechanical ventilation and 100% inspired oxygen for persistent hypoxemia, responded to tolazoline hydrochloride therapy. Early institution of antibiotics and aggressive ventilatory and pharmacological support were considered to be important factors in survival.


Otogenous tetanus: a sequelae of chronic ear infections. Eight patients had bacteriologically confirmed otogenous tetanus and all survived, suggesting that this may be a less severe form of the disease. Clostridium organisms most probably secondarily infect the purulent ear discharge after contamination by dirty cloth or fingers. Since most cases of tetanus are seen first by pediatricians or family physicians, they should be familiar with this potential source. Adequate tetanus immunization predisposed to chronic otorrhea.


Systemic reactions to influenza B vaccine. Standard whole virus influenza vaccine (1974-1976) containing 700 chicken cell agglutinating (CCA) units of type A (Port Chalmers/1/75) or Port Chalmers plus Scotland/840/74) and 500 units of type B (HK/8/73) antigens was found to produce excessive systemic toxicity in adult volunteers. Using experimental monovalent A and B vaccines, most of the observed toxicity was shown to be associated with the B antigen. Injection of 500 CCA units or more of B vaccine was followed within 10-16 hours by malaise and chills in approximately one-third of vaccines. Chills, malaise, and local pain were more common in volunteers lacking prevaccination serum HI antibody than in those in whom this antibody was present. Toxicity was not related to the presence of endotoxin or bacterial contamination of vaccine; it appeared to be "intrinsic" to the viral antigen. The mechanism for the toxicity in man may be the same as the direct pyrogenic effect of influenza antigen for rabbits previously observed by others. Detoxification of the B antigen by prolonged exposure to formalin reduced the side effects of a 500 CCA unit dose to acceptable levels without impairing its antigenicity.


Nature of the mutation in adult beta-galactosidase deficient patients. Fibroblasts from three chronically affected, beta-galactosidase deficient adults were shown to synthesize nearly normal quantities of immunologically reactive catalytically deficient beta-galactosidase, indicating that they are CRM + structural mutants.


Evaluation of a self-instructional unit for use in educational programs in histologic technique. A linear programmed instructional booklet was developed and used to evaluate the acceptability of this learning strategy to histologic technique instructors and their students. Comparisons of students' cognitive knowledge of the relevant topics before and after using the booklet indicated that most were achieving the booklet's objectives. The post-test score was not significantly affected either by prior experience with programmed materials or by the way the booklet was used. The verbal attitude responses of the students were encouraging, and most indicated the booklet was an efficient way for them to learn, and it was helpful in clarifying concepts. The verbal attitudes of the instructors were also favorable. The indications were that booklet use shortened subsequent lecture time and that the booklet was most valuable as a supplement to conventional instructional methods.


The evolution of a computer-assisted hematology system. Over a one-year period, the York Hospital customized and refined an existing software package and developed a computerized hematology system which solved many of the problems encountered while implementing the computer in the routine hematology laboratory. These problems included: developing an efficient system of internal organization and work flow patterns; finding a method for accurate and rapid test result entry; and ensuring the compatibility between the system and existing instrumentation.


Behavioral research on severe and profound mental retardation (1955--1974). A bibliography of behavioral research on severe and profound mental retardation was presented and briefly summarized. The review documented a dramatic shift in thinking about this population that has occurred in the last 20 years.