The epidemiology and treatment of depression when it coexists with somatoform disorders, somatization, or pain.

This article reviews the relationship between depressive disorders and somatoform disorders, somatization, and pain. These disorders and symptoms are clinically interrelated, yet the nature of the interrelation is not well understood. This review of the literature from 1975 through mid-year 1990 addresses the epidemiology and treatment of these conditions and/or symptoms when they occur together. When robust criteria are used to determine which publications are included, only 14 are available that address depressive disorders, somatoform disorders, and somatization. Similarly, there are only 13 that address depressive disorders and pain. Taken together, these studies indicate that 1) in somatization disorder patients, there is a high prevalence of depression; 2) in patients with major depression, there are substantial levels of hypochondriacal and somatizing symptoms; 3) that depression in the face of coexisting somatization disorder can be successfully treated; 4) in chronic pain patients, there is a high prevalence of depressive disorders; 5) in patients with major depression, pain is a frequent complaint; 6) and finally, that pain improves with the treatment of depression. What is most striking from this review, however, is the very limited number of studies that address these important problems. This lack of research-based data calls for new aggressive research efforts in this area.


The pathogenesis of Munchausen syndrome. A review and case report.

The authors present a case of Munchausen syndrome notable for an extended premorbid length and lack of early identifiable antisocial behavior. The patient's life history has been reconstructed, and an integrated psychobiological evaluation of the patient is given including neuroanatomical, neurohormonal, and neuropsychological assessments. Frontotemporal cerebral atrophy and lack of thyroid-stimulating hormone response to thyroid-releasing hormone infusion were found. Although self-object losses did appear to precipitate the Munchausen syndrome in a step-wise fashion, it appears that central nervous system deterioration might have been related to the development of the disorder.


Terminal cardiomyopathy, splitting, and borderline personality organization.

A 63-year-old married man with idiopathic terminal cardiomyopathy was admitted to the medical service for treatment of advanced heart failure. A psychiatric consultation was requested to assist the medical treatment team in dealing with the patient's abusive behavior. The case is presented and discussed within the context of understanding the borderline personality in the medical setting.


Anaphylaxis due to latex allergy.

An anaphylactic reaction to latex is reported in two patients. One occurred intraoperatively with exposure to the surgeon's latex gloves and the other during vaginal contact with a latex condom. Radioallergosorbent test (RAST) and scratch test with latex material identified the allergen. With the increasing use of latex gloves and condoms, one should be aware of the possibility of a severe immediate hypersensitivity reaction to latex products. Latex allergy should be considered when evaluating intraoperative and idiopathic anaphylaxis.


Prevalence of latex sensitivity in children evaluated for inhalant allergy.

We prospectively examined 80 children referred to a university allergy/immunology clinic for evaluation for inhalant allergies to determine the prevalence of latex hypersensitivity in this group. All children were skin tested with a Multi-test device to 35 inhalant allergens and a latex glove extract. Only one child gave a questionable history of latex sensitivity, but her skin test was negative. Three of 44 (6.8%) atopic children had a positive latex skin test (wheal greater than 4 mm); none of the 36 nonatopic children had a positive latex skin test. Two of the three children had a history of two or more surgical procedures but denied any clinical hypersensitivity reactions during surgery. Previous reports have demonstrated a personal history of atopy and of surgical procedures as risk factors for the development of latex hypersensitivity. This study helps verify these risk factors and should increase the awareness of this possible health hazard in this select group of children.


Idiopathic anaphylaxis: diagnostic variants and the problem of nonorganic disease.

We report on an expanding series of cases of idiopathic anaphylaxis (IA) with development of a classification, therapeutic regimens, and control of disease and induction of remission. Simultaneously, a growing series of cases referred for diagnosis and management of IA do not have IA. These cases, which approximate 10% of our series of IA cases, present serious time-consuming diagnostic problems for physicians. We present a series of nine cases of this type of nonorganic disease and describe the presenting symptoms, failure to document clinical abnormalities, and the lack of a response to a regimen shown to be effective in altering the course of true IA. The classification of IA has been expanded to include IA variants for patients in whom the symptoms complex varies significantly from other types of IA. Diagnostic suggestions and the problems of management are reviewed.


Bilateral posterior optic neuropathy after bilateral radical neck dissection and hypotension.

A 67-year-old man became totally blind after bilateral neck dissection complicated by postoperative hypotension. Histopathological study revealed extensive bilateral infarction of the orbital portion of the optic nerves.


A cross-sectional survey of 46 employees exposed to trimellitic anhydride.

This is a report of 46 employees exposed to trimellitic anhydride (TMA). The evaluation consisted primarily of periodic serum antibody studies and a questionnaire that identified symptoms compatible with allergic asthma and/or rhinitis, late respiratory systemic syndrome (LRSS), or pulmonary disease anemia (PDA) syndrome. Industrial hygiene data from the plant in 1989 reported exposures that were lower than levels in 1979. Seven employees had positive IgE antibody against trimellityl-human serum albumin (TM-HSA); one had TMA rhinitis, and another possibly had TMA asthma/rhinitis. Fourteen employees had positive IgG antibody against TM-HSA of whom only three had titers high enough to cause disease, and none of them had symptoms compatible with LRSS or PDA. At most, two workers had asthma or rhinitis during the 1990 evaluation. In summary, in this employee population with low level TMA exposure there is a low incidence of immunologically mediated disease due to TMA.


Surgical results and complications of goniosynechialysis.

Goniosynechialysis (GSL) was performed in 70 eyes with primary angle-closure glaucoma in which the intraocular pressure (IOP) could not be controlled with laser or surgical iridectomy. Following GSL, the IOP was maintained at below 20 mmHg, with and without eye drops, in 34 (87%) of 39 aphakic eyes and in 13 (42%) of 31 phakic eyes. In 8 of 10 eyes, all of which were phakic and the first GSL procedure was not effective, IOP could be controlled by a second GSL procedure combined with lens extraction. Life-table analysis showed a significant difference between the probable success rate, after 5 years, between the phakic and aphakic groups. Postoperative tonographic C values showed improvement in outflow facility. However, frequently encountered complications were exudation of fibrin and minor hemorrhage. Our results suggest that a combination of GSL and extraction of the lens may be necessary to control refractory angle-closure glaucoma.


Treatment of persistent epithelial defects in neurotrophic keratitis with epidermal growth factor: a preliminary open study.

We report three patients with persistent epithelial defects in the context of neurotrophic keratopathy that healed while on treatment with topically applied, mouse-derived epidermal growth factor (m-EGF). The clinical course of these patients was striking and suggests that EGF may have a potential role in the treatment of persistent epithelial defects in subjects suffering from neurotrophic keratitis.


Unilateral congenital corneal staphyloma with retinal neovascularization. A case report.

I present the light microscopic and ultrastructural findings in an unusual case of unilateral congenital corneal staphyloma. The anterior segment exhibited features of extensive Peters' anomaly whereas the posterior segment showed marked preretinal neovascularization and lack of axons as well as outer segments. These retinal changes might be secondary due to raised intraocular pressure and traction phenomena, but the complexity and extent of the described malformation argue against this.


Electrophysiological findings in paraneoplastic retinopathy.

Paraneoplastic retinopathy is a cancer-related non-metastatic retinopathy mainly associated with lung cancer. We examined two patients with presumed paraneoplastic retinopathy, both ophthalmologically and electrophysiologically. Both patients presented with initial visual complaints of moderate reduction of visual acuity. No specific fundus anomaly was found in the fundus except for a mild attenuation of the retinal arteries. The electroretinogram and pattern reversal visual evoked responses were either markedly reduced in amplitude or non-recordable. The electrooculogram recorded in one patient demonstrated a markedly reduced light peak/dark trough ratio. These results indicate the presence of a severe and diffuse bilateral retinal dysfunction, despite the relatively good visual acuities and mild fundus changes. Electrophysiological evaluations play an important role in the diagnosis of paraneoplastic retinopathy.


Morphological changes in ocular surface in dry eyes and other disorders by impression cytology.

A study was conducted on 107 eyes of 70 patients with dry eye disorders and mechanical and chemical extrinsic alterations and 64 eyes of 32 control subjects in order to describe a possible specific response of the conjunctival and corneal surface. We found the presence of "snakelike" chromatin cells and other nuclear changes, squamous metaplasia, and inflammatory cells in the conjunctiva in all groups. A decrease in goblet cell densities was also found in all groups, except for patients with blepharoconjunctivitis. The corneal cells were slightly larger in patients with keratoconjunctivitis sicca.


Whiplash and its effect on the visual system.

Whiplash or indirect injuries to the neck as a consequence of motor vehicle collisions are a common occurrence in which the frequency of ocular complications is largely unknown. Ophthalmic and oculomotor function was investigated in a longitudinal study of 39 cases who had their initial ophthalmological assessment within one week of the whiplash injury. Ten of 39 cases had ocular symptoms and signs which developed shortly after the accident. The principal abnormality in 6 of these was decreased convergence and accommodation, superior oblique muscle paresis in 2, decreased stereoacuity in 1 and bilateral vitreous detachments in 1 patient. All but 2 had complete resolution of their symptoms within 9 months. Four other patients were asymptomatic but had ophthalmic signs which resolved within 3 months. Oculomotor abnormalities following whiplash injuries are generally mild, have a good prognosis, and would appear from this study to be commoner than hitherto expected.


Conjunctival cytology in asymptomatic wearers of soft contact lenses.

Conjunctival epithelium was systematically investigated with impression cytology in clinically asymptomatic wearers of soft contact lenses who had been using their lenses for several years. Severe abnormalities were observed, which had so far only been seen in diseases of the ocular surface mainly in dry eye syndromes. All patients showed evidence of squamous metaplasia with distinctly enlarged, flattened cells without evidence of keratinization. They also showed frequent nuclear abnormalities, primarily a high percentage of snakelike-appearing condensations of nuclear chromatin (snakes). The goblet cell density observed was relatively low. Snakes were for the first time detected outside the known localization (upper bulbar conjunctiva, 12 o'clock position) and could be demonstrated throughout the whole bulbar conjunctival epithelium. It is suggested that the changes observed are due to chronic mechanical irritation by the contact lens, as indicated by their topographical distribution and as proven by their reversibility after omission of contact lens wear.


Abnormal sclerocytes in nanophthalmos.

Scleral tissue from a nanophthalmic patient was examined morphologically and by a tissue culture method. Collagen in the unusually thickened scleral tissue was arranged in irregularly interlacing bundles. Results of tissue culture studies showed sclerocytes that seemed to secrete many granules that stained positively with Alcian blue and periodic acid-Schiff (PAS). No granules were seen in cells of scleral tissue cultured from two control eyes. These findings may be the result of the modified glycosaminoglycan metabolism, which in turn contributes to the abnormal packing of collagen bundles and thickening of sclera in nanophthalmos.


Exuberant epibulbar tumor penetrating into the orbit in xeroderma pigmentosum.

The clinical and histopathological findings are described in a 10-year-old girl with xeroderma pigmentosum and multiple ophthalmic complications, including the eyelids, conjunctiva, orbit, cornea and iris; some of these complications took an unusual form. Histological examination following right orbital exenteration revealed an epibulbar squamous cell carcinoma penetrating the orbit and building a noose all around the ocular globe with subsequent strangulation. Moreover, a palpebral squamous cell carcinoma developed independently from the right lower lid and, unconnected with the epibulbar tumor, penetrated to the orbit.


Foveal flicker-fusion frequencies: a simple, new apparatus (4F).

While spatial resolution may be easily assessed with contrast-sensitivity frequency (CSF) data, determination of foveal flicker-fusion frequency (4F) is a simple method of providing the ophthalmic practitioner with accurate information about temporal resolution. The authors describe a simple apparatus that controls luminance, light intensity, light intervals, stimulus size, homogeneity of background illumination, and binocular gaze, especially when using two wavelengths, allowing an increased number of applications with reliable and comparable results. It may prove to be a useful tool for screening, clinical and subclinical assessment, and for evaluating visual acuity, also during follow-up.


Severe visual loss associated with retinal telangiectasis and facioscapulohumeral muscular dystrophy.

Facioscapulohumeral (FSH) muscular dystrophy is known to be associated with retinal telangiectasis. However, there are only few reports of severe visual loss due to exudative complications, so the risk to vision has not been established. Because of the possible therapeutic implications, we have described two cases of young girls who developed FSH muscular dystrophy and exudative retinal detachment due to telangiectasis. In the first patient, the severity of the disease precluded visual recovery despite extensive photo- and cryotherapy. In the other, visual acuity in both affected eyes was retained after treatment. Fundus examinations in young children at risk of having the gene for FSH muscular dystrophy may be justified so that retinal vascular disease can be detected before it becomes untreatable.


C-myc oncogene expression in ocular melanomas.

We have investigated the expression of c-myc in 24 ocular melanomas by immunohistochemistry, using two monoclonal antibodies raised against a mid-sequence portion of the c-myc product (6E10) and against the C-terminus (9E10). The results were compared with other putative prognostic factors, including tumour size, cell type, proliferation index (determined by flow cytometry), and ploidy, as well as immunohistochemical staining for HMB-45 and S-100 antigens. Staining, often focal, for c-myc was found in both the nucleus and the cytoplasm of a proportion of the cells in most tumours studied. Total cell staining for myc protein correlated with proliferative index in diploid tumours; seven out of nine aneuploid and mixed aneuploid/diploid cells showed strong staining in at least one cellular compartment. A positive correlation with myc expression was also found for HMB-45 staining, but not for cell type or staining for S-100. The results support the hypothesis that myc protein is involved in cellular proliferation in uveal melanomas and indicate that immunohistochemistry for myc antigen may be a useful prognostic marker in these tumours.


Axial myopia in eyes with optic nerve hypoplasia.

Given that abnormal visual experience during post natal development interferes with emmetropization, we proposed that eyes with hypoplastic optic nerves were predisposed to the development of refractive errors. Six of 14 patients with unilateral optic nerve hypoplasia and 5 of 22 patients with bilateral involvement had at least 4 D of myopia. Nine of the 11 patients with asymmetric bilateral involvement had relative myopia in the eye with the more abnormal optic nerve; none of the patients with symmetric bilateral involvement had a significant interocular refractive difference. Analysis of axial length measurements obtained in 10 of the 11 patients with high myopia showed a significant increase in total axial length. The presumed normal eye of patients with unilateral involvement was significantly smaller than the mean value for age-adjusted normals. We suspect that visual input to the central nervous system is one of the feedback signals involved in the regulation of ocular growth.


Dosing problems in the use of topical ophthalmic drops.

The effect of two drops of the same drug, one instilled immediately after the other, was compared to the effect of a single drop in 100 healthy volunteers. The drugs investigated were tropicamide, 0.125%, and phenylephrine, 2.5%. The mydriatic effect of two drops was 30%-35% stronger than the effect achieved by a single drop.


Electrophysiological and morphological changes in rabbit retina after exposure to the light of the operating microscope.

Healthy adult rabbit eyes were exposed to up to 4 h of continuous illumination with moderate light intensity, as is produced by the lamp of an ophthalmic operating microscope. Electroretinograms were recorded before and after the long period of illumination. The depression of the waves in the electroretinograms observed just following light exposure recovered within 1 h to normal values. Electron microscopy of the retina revealed changes within the cells of the pigment epithelium. These results are discussed in view of their clinical implications in human patients.


Regional differences in the distribution of cytoskeletal filaments in the human and bovine ciliary epithelium.

The distribution of the cytoskeletal elements cytokeratin 18, vimentin, desmin, glial fibrillary acid protein (GFAP), and actin was investigated in different portions of the ciliary body of human and bovine eyes. Regional differences were found only for vimentin and cytokeratin. In both species, cytokeratin staining was more intense in the pigmented (PE) than in the nonpigmented epithelial (NPE) cells. In contrast, immunostaining for vimentin was more intense in the NPE than in the PE. The most intense immunoreactivity for cytokeratin 18 in the PE and for vimentin in the NPE was observed in the posterior pars plana and the crests of the pars plicata. In the remaining portions of the ciliary body, staining was reduced or absent. Desmin and GFAP were not found in the ciliary epithelial cells, whereas actin filaments occurred in both cell layers in all regions.


Histopathologic findings in eyes treated with a ruthenium plaque for uveal melanoma.

Fifty-six globes that had to be enucleated following ruthenium plaque therapy were examined histopathologically. These eyes account for 10% of all uveal melanomas treated at the University Eye Clinic Essen up until 1985. All but one revealed at least some supposedly viable tumor cells. The most prominent findings within the tumors were tumor cell necrosis, vacuolization and balloon cell degeneration, vascular obstruction and fibrosis of the tumor stroma with accumulation of pigmented macrophages. Tumor necrosis was complete or nearly complete in five cases. Tumor regression correlated with cell type and pigmentary characteristics of the tumor, with epithelioid and heavily pigmented tumor cells being more radiosensitive. Tumor regression was inhomogeneous, possibly due to polyclonality, with tumor cells of varying radiosensitivity, or due to patchy areas of vascular obliteration. Among other ocular structures, extensive subretinal gliosis, chorioretinal atrophy and scarring of the sclera within the field of radiation were observed. Scleral necrosis was present in only five cases and was limited to areas in which the tumor had infiltrated the deep scleral layers. The findings described were considered to reflect radiation injury rather than spontaneous tumor regression when compared to 70 control eyes that had been enucleated without prior treatment for uveal melanoma.


UV-C irradiation-induced peroxidative degradation of microsomal fatty acids and proteins: protection by an extract of Ginkgo biloba (EGb 761).

After exposure of rat liver microsomes to UV-C irradiation, analysis of membrane fatty acids by gas chromatography confirmed that EGb 761, a drug containing a dosed and standardized extract of Ginkgo biloba, provides effective protection against free radical attack in vitro. This analysis, coupled with thiobarbituric acid (TBA) reaction, permitted qualitative and overall quantitative evaluation of radical-induced damage to polyunsaturated fatty acids (PUFA), as well as evidence of the antioxidant properties of the Ginkgo biloba extract. Assay of thiobarbituric acid reactive substances (TBARS) showed a correlation between TBARS concentration and the state of degradation of the polyunsaturated fatty acids. Mannitol (5.5 mM) did not prevent degradation of microsomal PUFA or malondialdehyde (MDA) production, nor did it prevent polymerization of membrane proteins. Low doses of EGb 761 were found to provide efficient protection of membrane PUFA regardless of individual susceptibility to peroxidation. This protection was accompanied by a decrease in the production of TBARS. EGb 761 also protected membrane proteins from the irreversible polymerization induced by these degradation products, but did not appear to prevent thiols oxidation into disulfide bonds.


The site of nonenzymic glycation of human extracellular-superoxide dismutase in vitro.

The secretory enzyme extracellular-superoxide dismutase (EC-SOD) has affinity for heparin and some other sulfated glycosaminoglycans and is in vivo bound to heparan sulfate proteoglycan. Nonenzymic glycation of EC-SOD, both in vivo and in vitro, is associated with a reduction in heparin affinity, whereas the enzymic activity is not affected. The glycation sites in EC-SOD are further studied in the present article. It is shown that modification of a few of the five lysyl residues of the subunits of the enzyme with trinitrobenzene sulfonic acid nearly abolishes the in vitro glycation susceptibility. From a chymotryptic digest of in vitro glycated EC-SOD, two peptides with affinity for boronate could be isolated. Amino acid sequence analysis showed that both encompassed the carboxyterminal end. epsilon-Glucitol lysine was identified in both peptides at positions 211 and 212. The primary glycation sites in EC-SOD are thus lysine-211 and lysine-212 in the putative heparin-binding domain in the carboxyterminal end.


Effects of recombinant human extracellular-superoxide dismutase type C on myocardial infarct size in pigs.

The efficacy of human extracellular-superoxide dismutase type C (EC-SOD C) to limit infarct size after ischemia and reperfusion was explored and compared to that of EC-SOD C combined with catalase (CAT) and to that of CAT alone. EC-SOD C binds to heparan sulphate proteoglycan on the cell surfaces. Thirty-two pigs were subjected to 45 min of myocardial ischemia followed by 4 h of reperfusion. Control pigs (group A; n = 8) received 300 mL of saline into the great cardiac vein during a 30-min period started 5 min prior to reperfusion; pigs in group B (EC-SOD C; n = 8) got 16.6 mg of EC-SOD C; pigs in group C (EC-SOD C + CAT; n = 8) got 16.6 mg of EC-SOD C together with 150 mg of CAT. Pigs in group D (CAT; n = 8) received 150 mg of CAT. In groups B, C, and D, the drug was dissolved in saline and infused into the great cardiac. Infarct size expressed as percent of area at risk was smaller in groups B (14.5 +/- 16.7%) and C (40.8 +/- 13.3%) than in groups A (78.8 +/- 8.6%) and D (67.2 +/- 18.6%; p less than .05). Creatine kinase (CK) activity in ischemic myocardium was higher in groups B (1740 +/- 548 U/g) and C (1729 +/- 358 U/g) than in groups A (1184 +/- 237 U/g) and D (1251 +/- 434 U/g; p less than .05). There was an inverse relation (r = -.83) between infarct size and CK content. The EC-SOD C infusions resulted in only minimal increases in plasma SOD activities. In conclusion, the presence of SOD on the cell surfaces is of importance in the prevention of reperfusion injury rather than circulating SOD.


Peroxidation of lipid emulsions: a hazard for the premature infant receiving parenteral nutrition?

Lipid emulsions for parenteral use are peroxidized during storage, indicating that the amount of the natural vitamin E in the preparations is inadequate. Peroxidation products in the lipid emulsion preparations can induce cell damage in vitro. The parenteral administration of lipid emulsions increases in vivo lipid peroxidation in adult and healthy newborn patients as well as in premature infants, whereas enteral feeding seems to lead to a more balanced accretion of polyunsaturated fatty acids. The use of parenteral lipids has recently been associated with increased morbidity of premature infants. Current opinion favors the view that evolution of the complications is highly influenced by the inferior defense of the premature infants to resist oxidant loads. A novel antioxidant added in the preparations for the intravenous provision of polyunsaturated lipids could be beneficial for such patients.


Electronic properties and free radical production by nitrofuran compounds.

Substitution of nifurtimox tetrahydrothiazine moiety by triazol-4-yl, benzimidazol-l-yl, pyrazol-l-yl or related aromatic nitrogen heterocycles determines changes in the quantum chemistry descriptors of the molecule, namely, (a) greater negative LUMO energy; (b) lesser electron density on specific atoms, especially on the nitro group atoms, and (c) modification of individual net atomic charges at relevant atoms. These variations correlate with the greater capability of nifurtimox analogues for redox-cycling and oxygen radical production, after one-electron reduction by ascorbate or reduced flavoenzymes. Variation of the nitrofurans electronic structure can also explain the greater activity of nifurtimox analogues as inhibitors of glutathione reductase and Trypanosoma cruzi growth, although other factors, such as molecular hydrophobicity and connectivity may contribute to the latter inhibition.


The use of fluorescent probes to assess oxidative processes in isolated-perfused rat heart tissue.

The formation of reactive oxygen species (ROS) in intact heart tissue has been assessed by direct ESR measurements, and indirectly by the formation of characteristic tissue products and the protective effects of various antioxidants. The development of lipid soluble esters of compounds which can be trapped intracellularly after hydrolysis, and which fluoresce after oxidation, has provided a new tool to investigate ROS in vitro. The utility of 2',7'-dichlorofluorescin diacetate (DCFDA) in isolated-perfused rat heart tissue was investigated in the present study. DCFDA and its deacetylated form were incubated with various levels of hydrogen peroxide or t-butylhydroperoxide (tBOOH). Conversion of the diacetate form to a fluorescent product required 4-5 h with hydrogen peroxide and up to 24 h with tBOOH. In contrast, the deacetylated form fluoresced at 80% of maximum levels 1 h after the addition of 100 mM tBOOH. DCFDA was loaded into heart tissue by infusing for 10 min at a final concentration of 10 microM in Krebs-Henseleit bicarbonate buffer. After a 10 min washout period, analysis of freeze-clamped heart tissue revealed that the trapped material was readily converted to a fluorescent product by tBOOH, indicating hydrolysis had occurred. Fluorescence of material trapped in heart tissue was approximately 24% of the maximum achieved after oxidation with 100 mM tBOOH. This value decreased to 18 and 13% when the loading and washout periods were from 0 to 20 or 10 to 30 min of hypoxia, respectively. Similar results were obtained with the less readily oxidized dicarboxy derivative of DCFDA. Infusion of 500 microM tBOOH increased the oxidation of DCFDA in heart tissue from 24 to 31%.(ABSTRACT TRUNCATED AT 250 WORDS)


Formation of stable free radicals from kampo medicines TJ-9, TJ-15, TJ-23, TJ-96, TJ-114 and their antioxidant effect on low density lipoproteins.

The Japanese herbal Kampo medicines TJ-9 (A), TJ-15 (B), TJ-23 (C), TJ-114 (D) and TJ-96 (E) were effective (2-5x less than alpha-tocopherol) in inhibiting a copper-induced peroxidation of low density lipoprotein. Kampo medicines dissolved in n-butanol formed stable free radical(s), detected by EPR spectroscopy as a single asymmetric line with g-value g = 2.005. The radical concentration increased in the order: C less than D approximately A approximately E less than B. When the Kampo medicines were oxidized in n-butanol by excess of PbO2 their radical concentration increased 7-15 fold and was in the order C less than D less than A approximately E much less than B. A relationship between the potency of the medicines to inhibit peroxidation of LDL and their ability to form stable free radicals upon oxidation was observed. The medicine which formed more radicals was more efficient in inhibiting peroxidation of LDL. In order to study whether Kampo medicines can reduce alpha-tocopherol radical, the alpha-tocopherol radical was generated by the reaction of alpha-tocopherol with UV irradiated di-tert-butylperoxide and by autooxidation of alpha-tocopherol in n-butanol (25 microliters ml-1) in air. In both systems vitamin-C greater than Kampo B decreased the concentration of the alpha-tocopherol radical and the EPR spectrum of Kampo B stable radical(s) appeared. The effect of other Kampo medicines was not clearly seen since their EPR spectra were superimposed with the spectrum of the alpha-tocopherol radical. The results indicate that Kampo medicines possess electron donor properties and ability to form stable radical(s). The results may contribute to understanding beneficial effects of Kampo medicines in diseases in which free radical damage is suggested.


Scavenging of lipid peroxidation products from oxidizing LDL by albumin alters the plasma half-life of a fraction of oxidized LDL particles.

We analyse LDL oxidation in vitro in the presence of copper (II) ions and differentiate a lag phase and a rapid peroxidation phase. We demonstrate that a physiological concentration of albumin does not alter the kinetics of the dienes in the oxidizing LDL but reduces the fluorescence of the oxidizing LDL and alters the biological properties of oxidized LDL. We find in rats after intravenous administration of oxidized LDL, that it is rapidly cleared from the circulating blood. The presence of albumin during the peroxidation phase, however, reduces the fraction of oxidized LDL with rapid blood clearance. We propose that some lipid peroxidation products formed in oxidizing LDL are hydrophilic enough to diffuse into the aqueous buffer from where they react either with the epsilon-amino-groups of apolipoprotein B or albumin. Effective scavengers for these hydrophilic endproducts of the LDL oxidation pathways such as albumin might reduce modification of the LDL and might be useful to reduce its atherogenicity.


Oxidative damage in the red cells of vitamin E-deficient rats.

One month-old male Sprague-Dawley rats were maintained on a basal vitamin E-deficient diet supplemented with either 0 or 50 ppm vitamin E for 5 months. Washed red blood cells were resuspended in phosphate buffered-saline, pH 7.4, that contained 0-50 mM glucose and 0-20 mM ethylenediamine tetraacetic acid (EDTA), and were incubated at 37 degrees C for up to 22 h. Contrary to expectations, glucose in the incubation medium accelerated, rather than retarded, the rates of hemolysis, lipid peroxidation and methemoglobin formation in the vitamin E-deficient cells. EDTA, on the other hand, partially inhibited the extent of oxidative damage. Vitamin E-supplemented cells were resistant to oxidative damage in the presence or absence of glucose and/or EDTA. The levels of reduced glutathione (GSH) and activity of catalase were decreased faster in the vitamin E-deficient cells than the supplemented cells, and the rates of their decline were slowed down by either glucose or EDTA. The activities of GSH peroxidase and superoxide dismutase were not significantly altered in the red cells of either group during incubation. The results obtained suggest that reactive oxygen species and reduced metal ions play important roles in initiating oxidative damage to the red cells of vitamin E-deficient rats. However, the agent responsible for initiating the hemolytic event has yet to be established.


We report on the chemical characterization of DNA base damage in chromatin of gamma-irradiated cultured human cells. Chromatin was isolated from unirradiated and irradiated cells and analyzed by gas chromatography/mass spectrometry with selected-ion monitoring after acidic hydrolysis of chromatin and trimethylsilylation of hydrolysates. Prior to analysis of chromatin samples, experimental conditions for acidic hydrolysis were optimized by determining the relative molar response factors of modified bases under non-acidic and acidic conditions, and their release from DNA under various acidic conditions. A number of modified bases in chromatin isolated from irradiated cells were identified and quantitated. These were 5-hydroxy-5-methylhydantoin, 5-hydroxyhydantoin, 5-(hydroxymethyl)uracil, cytosine glycol, thymine glycol, 5,6-dihydroxycytosine, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, 2-hydroxyadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 8-hydroxyguanine. Radiation doses ranging from 42 to 420 Gy (J.kg-1) were used. Background levels of all modified bases were observed in chromatin isolated from unirradiated cells. The radiation yields of a number of modified bases were increased significantly over their background levels at a dose as low as 42 Gy. In most cases, linear dose-yield relationships were obtained up to approximately 200 Gy. At radiation doses higher than 420 Gy, no additional increase in the yields of modified bases was observed. The yields of guanine-derived bases amounted to approximately 45% of the total net yield of modified bases measured, followed by almost equal yields of adenine-, cytosine- and thymine-derived bases. Modified bases identified were typical products of hydroxyl radical attack on DNA bases, indicating the involvement of hydroxyl radical, although their induction in part by the direct effect of ionizing radiation through ionization of DNA bases cannot be excluded. The yields of modified bases were lower than those previously measured after gamma-irradiation of fully expanded chromatin in aqueous buffer solutions.


Limited protection against iron-induced lipid peroxidation by cord blood plasma.

The ability of plasma from newborn babies (cord blood) and adults to inhibit iron-induced lipid peroxidation was compared. The caeruloplasmin and transferrin concentrations, and latent iron-binding capacity were lower in the babies (p less than 0.001). The plasma of many of the babies had no latent iron-binding capacity and contained non-protein-bound iron (measured by the bleomycin assay). The in vitro ability of plasma to inhibit iron-induced liposome peroxidation by either ferroxidase antioxidant activity (caeruloplasmin) or iron-binding antioxidant activity (transferrin) was measured. The antioxidant activity in both assays was decreased in the babies (p less than 0.001). The percentage inhibition of peroxidation in the iron-binding antioxidant assay correlated positively with the latent iron-binding capacity (p less than 0.001) and negatively with the presence of bleomycin-detectable iron (p less than 0.02) in the babies. This assay produced stimulation of peroxidation in 42% of the babies but none of the adults. The diminished capacity of cord blood plasma to prevent iron-induced lipid peroxidation may predispose the newborn baby to the toxic effects of oxygen.


Development of a simple antioxidant screening assay using human skin fibroblasts.

The purpose of this study was to develop a simple antioxidant screening assay for quantifying the protective effects of antioxidant enzymes, inhibitors and scavengers against extracellularly generated oxygen species on human skin fibroblast cytotoxicity. Different in vitro oxidative stresses have been studied: xanthine oxidase-hypoxanthine, flavin mononucleotide-NADH, and hydrogen peroxide. Cytotoxicity and protection were evaluated by two procedures: evaluation of the living cells using a colorimetric method (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT), and ability of the viable cells to adherate and proliferate. Hypoxanthine-xanthine oxidase and H2O2 induced a dose dependent cytotoxicity only when we considered the delayed toxicity. The influence of the cell density was also investigated. The delayed toxicity was higher when cell density increased. One hundred percent protection against free radical cytotoxicity induced by the three systems were obtained with catalase (500 U/ml). When the oxidative stress used was H2O2 90-96% protection was obtained with deferoxamine an iron chelating agent that prevents iron catalysed radical reactions. Using the colorimetric method no significant protection was obtained when SOD was added before and during the stresses. Using the fibroblasts ability to proliferate SOD (10-150 micrograms/ml) reduced xanthine oxidase (20 U/l)-hypoxanthine (0.10-0.30 mM) or H2O2 (1-6 mM) cytotoxicity by 15-20%. SOD did not act as antioxidant when the applied stress was mediated by flavin. In this study we showed a paradoxical effect and the cytotoxicity of flavin-NADH system increased when we added SOD to the cell medium. This simple and reliable antioxidant screening assay required no costly or radioactive equipment.


Thiol compounds as protective agents in erythrocytes under oxidative stress.

The potential for the thiol-containing drugs, N-acetyl cysteine and N-mercaptopropionyl glycine, to act as antioxidants intracellularly has been studied in erythrocytes under oxidative stress. The effects have been compared with that of the glutathione peroxidase inhibitor, mercaptosuccinate. The results show differential responses of sickle and normal erythrocytes to the thiol compounds. N-acetyl cysteine is the more efficacious with no toxic effects in these systems. N-Mercaptopropionyl glycine is not only limited in its ability to demonstrate antioxidant capacity in erythrocytes but also exerts deleterious effects.


Ischemia and reperfusion: effect of fructose-1,6-bisphosphate.

Several lines of evidence indicating a close relationship among ischemia, concentration of high-energy metabolites and onset of the "oxygen paradox" in reperfused tissues have been published. In this framework, we have recently studied the effects of exogenous fructose-1,6-bisphosphate on energy metabolism and on oxygen free radical damages of isolated rat heart subjected to anoxia and reoxygenation. In comparison with control groups, hearts perfused in the presence of 5 mM fructose-1,6-bisphosphate throughout the different perfusion conditions showed higher concentrations of energy metabolites at the end of anoxia, most of which were normalized after reperfusion. Furthermore, in comparison with control hearts, a reduction of tissue malondialdehyde and of lactate dehydrogenase release in the perfusate was observed in fructose-1,6-bisphosphate-perfused hearts. In this article we review most of the available data concerning the ability of fructose-1,6-bisphosphate to protect from ischemia and reperfusion damage outlining those recent findings which contributed both to clarify the pharmacological profile of the drug and to give an insight in its probable mechanism of action.


Effects of exogenous prostacyclin on placental blood flow, placental weight and fetal weight in normotensive and spontaneously hypertensive rats.

Recently, prostacyclin (PGI2) has been used for the treatment of preeclampsia. In this study, we investigated the effects of PGI2 on placental blood flow (measured with clearance of hydrogen gas generated by electrolysis) in normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The placental blood flow of PGI2-treated SHR (0.25, 0.5 and 1 mg/kg) was significantly (p less than 0.05) reduced compared with WKY. These data suggest that PGI2 has a certain reducing effect on placental blood flow in SHR; on the other hand, in WKY, it has an increasing effect depending on the dose.


The decidua of early human pregnancy: immunohistochemistry and function of immunocompetent cells.

Like the endometrial stroma, the decidua contains lymphoreticular cells, and these are probably involved in immunological interactions between the conceptus and the mother. Lymphoreticular cells in decidual tissue obtained from 12 patients undergoing therapeutic abortion of an intact pregnancy at 6-10 weeks' gestation were investigated in this study. Immunophenotyping with a broad panel of monoclonal antibodies revealed various subpopulations of lymphoreticular cells. Macrophages (Ki-M6+, Ki-M7+, Ki-M8+, KP1+, MAC 387+ and Ki-M1P+) represented the largest fraction of intradecidual lymphoreticular cells. CD3+ and CD8+ lymphocytes were found in moderate numbers and CD4+ cells in small numbers. The majority of the intradecidual lymphoid cells exhibited an unusual phenotype [CD7+, CD2+, CD56+, triple negative (CD3-, CD4-, CD8)]. The distribution of these unusual lymphocytes mirrored that of the so-called endometrial stromal granulocytes. A few of these stromal granulocytes reacted with the macrophage-associated antibody KP1, but not with Ki-M1P, another macrophage marker. This was confirmed by immuno-electron microscopy. The finding that intradecidual CD3+ lymphocytes express neither the alpha/beta nor the gamma/delta heterodimer of the T cell antigen receptor was unexpected. However, these cells did express the alpha/beta heterodimer after in vitro culture with PHA-P and recombinant exogenous interleukin-2. No stimulated T lymphocytes expressing activation antigens could be detected. B lymphocytes, T and B immune accessory cells and CD15+ granulocytes were found only in small numbers or were absent. Amongst cells expressing NK cell markers, CD57+ and CD16+ cells were found in small to moderate numbers, while CD56+ cells were detected in large numbers.(ABSTRACT TRUNCATED AT 250 WORDS)


Heparin neutralization by an extract of the human placenta: measurements and the concept of placental barrier to heparin.

A soluble extract from human placenta was found to neutralize heparin in a factor Xa-dependent heparin assay system. In comparison with serum the antiheparin activity of placenta tissue is 10 times higher (extract from 1 g of placenta neutralizes 8.94 +/- 3.31 IU of heparin; 1 ml of serum approximately 1 IU). The substance neutralizing heparin has not been identified, but it has been found that it is nondialyzable, is not adsorbed on heparin-Sepharose, and does not act progressively. It was suggested that the substance(s) responsible for the antiheparin effect in vitro might contribute to the failure of heparin to penetrate the placenta in vivo (placental barrier to heparin).


Action of alpha-methyldopa on human umbilical circulation in vitro.

To determine the possible effects of alpha-methyldopa on the motility of human umbilical artery, a total of 53 arterial segments were perfused with different concentrations of the drug as follows: 38 segments with 125, 250 and 500 ng/ml of the drug, 9 segments with 500 ng/ml alpha-methyldopa in combination with 10(-7) M yohimbine, and 6 segments with 10(-7) M yohimbine alone. alpha-Methyldopa had a vasoconstrictor effect at all doses employed, with a clear dose-effect correlation (p less than 0.01). The vasoconstrictor effect of 500 ng/ml alpha-methyldopa was fully inhibited in the presence of 10(-7) M yohimbine. These results suggest that alpha 2-adrenergic receptors are present in the umbilical circulation and that alpha-methyldopa may play a role in the control of this circulation.


Differential diagnosis of early human pregnancies: impact of different diagnostic measures.

A total of 261 women in early pregnancy, either with mild symptoms of ectopic pregnancy (EP) or being at an increased risk for this condition, were included in a longitudinal study. The effectiveness of different diagnostic measures in obtaining correct final diagnoses was analyzed. In addition to clinical findings and symptoms, the use of serum human chorionic gonadotropin, serum progesterone, endovaginal sonography and a risk score for EP were all proven to be valuable in distinguishing normal intrauterine pregnancies from pathological pregnancies.


Post-partum contraceptive preference in high-risk parturients in Maputo.

A total of 171 consecutive high-risk parturients in Maputo Central Hospital were studied regarding post-partum contraceptive choice in order to plan a new post-natal clinic approach in maternal health care. It was found that contraceptive interest was much less in women with experience of child loss than in women with all children surviving (p less than 0.005). The findings were useful in planning various measures to meet the documented demand for available methods under adverse circumstances of scarce manpower and material resources.


Endogenous estradiol and progesterone concentrations in smokers on oral contraceptives.

The simultaneous effects of cigarette smoking and oral contraceptives on serum estradiol and progesterone levels were investigated in 114 premenopausal women. Serum 17 beta-estradiol and progesterone levels were measured by radioimmunoassay. In smokers, estradiol and progesterone levels were significantly lower (p less than 0.025). In smokers using oral contraceptives, estradiol and progesterone levels were the lowest (p less than 0.001 and p less than 0.01, respectively). The findings suggest that smoking and oral contraceptives independently lower serum estradiol and progesterone concentrations in premenopausal women and that the effects may be additive.


Evaluation of the clinical method of measuring cervical dilatation after treatment of the cervix prior to first trimester abortion.

A comparison of the subjectively measured cervical dilatation and the dilatation measured objectively with a force-sensing instrument connected to metal dilators was made in two studies of cervical treatment prior to first trimester abortion. It was concluded that the subjective method is a sensitive and accurate method of measuring cervical dilatation but does not allow for comparison between different studies where an objective method of measurement should be used.


Evaluation of bone metabolic markers as indicators of osteopenia in climacteric women.

Lumbar bone mass (LBM) determination by quantitative computerized tomography in pre-, peri- and postmenopausal women was utilized to identify subjects at risk to develop osteoporosis. The results were related to determinations of bone metabolic markers (serum osteocalcin and urinary calcium excretion). Osteocalcin was the only metabolic marker which underwent significative changes. However, we found very poor correlations between LBM and metabolic markers and it is concluded that bone mass determination remains the method of choice to select women for preventive therapy.


Delay in the diagnosis of rupture of the uterus due to epidural anesthesia in labor.

A case report of uterine rupture in labor with epidural anesthesia is presented. The woman had good analgesia on the left side, but complained of severe labor pais on her right side. Uterine rupture occurred which was manifested by sudden vaginal bleeding, fainting, low blood pressure and fetal distress. She did not feel any pains typical of uterine rupture. Rupture of the left uterine wall, with a large hematoma in the left parametrium was seen at surgery. It seems the unilateral anesthesia of the left side concealed the early signs of rupture.


Maternal hemorrhagic complications following prophylactic low-dose aspirin and dipyridamole therapy.

A case is reported of a severe postpartum maternal hemorrhagic complication, which was related to prophylactic antithrombotic therapy with daily low-dose aspirin (75 mg) combined with dipyridamole (225 mg) for the prevention of preeclampsia. The postpartum course was complicated by recurrent episiotomy site hematomas of nonclotted blood and prolonged bleeding time. Transfusion of platelet concentrates was necessary to control the bleeding. This case report draws attention to maternal hemorrhagic complications which may be associated with prophylactic low-dose aspirin and dipyridamole in pregnancy.


Third trimester torsion of persistent ovarian cyst following ovarian hyperstimulation--an unusual cause of preterm labor.

Herein, a patient being operated for cesarean section due to preterm labor in the 31st week of a triplet pregnancy induced by gonadotropins is being described. On celiotomy, peritoneal effusion was present secondary to torsion of a 10 x 6 cm right ovarian cyst. This uncommon finding contradicts the common belief that the chances for an ovarian cyst in the overcrowded peritoneal space due to a 40-week-size uterus to twist around its pedicle are remote. The possibility that preterm labor was initiated by the torsion is discussed.


Independent origin of uterine leiomyomas with karyotypically identical alterations.

Cytogenetic investigation of multiple uterine leiomyomas from the same patient revealed karyotypes containing cytogenetically indistinguishable del(7)(q21.2q31.2) in two of the tumors. Since this finding seemed to contradict the conclusion from previous glucose-6-phosphate dehydrogenase studies of multiple uterine leiomyomas in which an independent origin of these tumors was found, we assessed clonal tumor origin by DNA-recombinant X-chromosome inactivation analysis. The two leiomyomas with del(7)(q21.2q31.2) had different inactivated X-chromosomes. This proves that they originated independently and indicates that their cytogenetic similarity was coincidental.


[Use of thrombolysis for myocardial infarction in Israel].

Thrombolysis is generally accepted as the initial treatment for acute myocardial infarction. The extent to which this therapy is being implemented in Israel and the reasons for exclusion of cases from thrombolytic therapy were prospectively investigated. 413 consecutive patients with acute myocardial infarction hospitalized during January 1990 in 18 of Israel's 25 coronary care units were studied. Thrombolytic therapy was administered to 145 patients (35%: 38% of the men and 29% of the women; NS). It was used more often in those up to the age of 75 (38%) than in those over (18%, p less than 0.005) and in those with a first or anterior infarction (40% and 48%, respectively) than those with recurrent or inferior infarction (23% and 31%, respectively; p less than 0.005 for both). The 2 most frequent reasons for not using thrombolysis were late arrival in the coronary care unit (33%) and absence of ST elevation on the admission electrocardiogram (28%). Hospital mortality was 6% in the thrombolytic group versus 20% in those ineligible for thrombolysis. The significance of this difference is not clear as there was no randomization to treatment.


[Hypertension in the community].

Hypertension is a major risk factor for cerebral and coronary disease and its early detection is very important for the family physician. We checked the implications of a hypertension survey in the community (from the age of 10 years) on the attitude of the primary care team. We found that although the medical team was aware of the significance of early detection and treatment of hypertension, according to the "law of halves" half the hypertensives were in treatment and of them half had normal blood pressure. This fact is probably not related to the quality of medical care. High risk groups identified were hypertensive patients who smoked, Jewish men of western origin, and Jewish women of Asian-African origin (who had a high rate of strokes). These groups were targeted for active intervention by the primary care team. This survey is part of planned community-intervention by the primary care team in the field of hypertension.


[Treatment of retinal detachment with intraocular expandable gas injection].

The injection of expandable gas into the vitreous is a new method for treating retinal detachment. The injected gas bubble seals the retinal break and allows absorption of subretinal fluid. In 12 patients, in all eyes treated by injection of sulfur hexafluoride, the detached retina became reattached. In 3 eyes (25%) detachment recurred. To achieve attachment again, both vitrectomy and the circling band operation were performed in 2 of them, and only the latter operation in the third. Risk factors for redetachment included detachment of the macula, retinal detachment larger than 5-o'clock-hours, and pseudophakia. Proper selection of patients for gas injection is most important.


[Familial breast cancer in Arabs].

500 surviving Arab cancer patients in follow-up were interviewed with regard to other cases of cancer in their families. Among 73 who had breast cancer, in 15 (20.3%) there was another case of breast cancer among first-degree relatives. The incidence of both primary and familial breast cancer was higher among Christian than among Moslem women. We conclude that Arab women with breast cancer in their families are at high risk for developing breast cancer themselves.


[Echinococcosis in pregnancy].

Hydatid disease affects sheep and cattle and is caused by the larval form of Echinococcus granulosus. Affected human beings are only chance intermediate hosts. We present a woman admitted in her 22nd week of pregnancy because of upper abdominal pain and persistent vomiting. The presumptive diagnosis of hydatid cyst of the liver was established by ultrasound, X-ray and CT examinations. At laparotomy a 10 x 7 cm hydatid cyst was removed from the liver. She recovered completely and delivered spontaneously at term. There was no evidence of hydatid disease in the newborn or in the placenta.


[Surgery for complete rectal prolapse in adults].

Surgery for complete rectal prolapse was performed in 17 women and 3 men between November 1986 and April 1991. An abdominal approach with posterior rectopexy was used in 17. The Thiersch procedure of anal narrowing was performed in 3 high risk patients. All recovered without major complications. Urinary tract infection developed in 15% and postoperative fecal impaction in 10%. Anal continence improved in 70% of those previously incontinent. There was no recurrence of complete rectal prolapse during follow-up. All patients rated the operative results as either good or very good.


[Idiopathic scrotal edema].

Idiopathic scrotal edema causes painful enlargement of the scrotum, as does torsion of the testis or of a testicular appendage, or epididymo-orchitis. Unilateral edema of the scrotum develops rapidly, the skin becomes pale pink or red, and there is discomfort rather than acute pain. Careful palpation reveals a nontender testis. The condition is usually self-limited, and resolves completely without treatment in 48 hours. It must be differentiated from testicular torsion, for which urgent surgical treatment is mandatory.


[Surfactant replacement therapy for respiratory distress syndrome: a pilot study].

A pilot study of the effect of exogenous surfactant (ES) on premature infants with respiratory distress syndrome (RDS) is reported. Each of the first 15 infants in this study received 200 mg/kg of natural surfactant (Curosurf) during the first day of life. Controls were 56 infants with RDS seen in the 15 months prior to the study. Within 5 minutes of starting ES, in all infants there was rapid and dramatic improvement in oxygenation and improvement in the average arterial/alveolar ratio of 169%. They had lower oxygen and ventilatory requirements than the control group throughout the first 5 days of life. No treated infant suffered from pulmonary air leak, while in the control group 21% developed pneumothorax and 11% had pulmonary interstitial emphysema. Mortality was 13% in the treated group as compared to 27% in the control group (p less than 0.01). There were no differences between the groups in the incidence of sepsis, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, or bronchopulmonary dysplasia, nor were there side-effects of therapy. Dosage, timing and composition of the ideal surfactant are important questions for future studies.


[Diathermy-induced gas explosion in the intestinal tract].

Surgical diathermy is widely used in modern operating rooms, although explosion in the gastrointestinal tract is a known serious complication. We report a case of colonic explosion following use of diathermy. Based on our experience and the available data, it is recommended that in cases of gastrointestinal tract obstruction, poor bowel preparation or following use of oral mannitol for bowel preparation, diathermy should be avoided in opening the gastrointestinal lumen.


[Implanted subcutaneous venous catheter for prolonged intravenous treatment].

Subcutaneous venous catheter devices were implanted in 104 patients between January 1989 and June 1991. In 90% the implantation was performed under local anesthesia as an ambulatory procedure. In 85% the catheter was implanted for long-term chemotherapy and in 15% for intravenous feeding, antibiotic treatment or dialysis. There were postoperative complications in about 10%, the most frequent being infection of the surgical wound or of the catheter canal. Venous thrombosis, cutaneous necrosis and catheter occlusion were observed in only 5%. The main advantages of the method are its convenience for the patient, ease of installation and low rate of complications. From our experience we conclude that the implanted subcutaneous venous catheter is a simple and effective procedure for prolonged intravenous treatment.


[Desmoid tumors].

Desmoid tumors in various anatomic sites were treated in 4 females and 3 males, ranging in age from 16-50 years, during a 6-year period. In 5 the tumor was completely excised with free margins. In the other 2 excision was incomplete and the tumor recurred within a few months. Desmoid tumors have a marked tendency to local recurrence, and therefore should be widely excised. There is no evidence that adjuvant therapy has a place in the management of these tumors.


[Repair of esophageal perforation with a diaphragmatic flap].

Perforation of the esophagus is life-threatening and requires prompt diagnosis. Immediate surgery with primary suture of the perforation is the treatment of choice. Any delay in diagnosis or treatment results in a sharp increase in mortality due to the combination of rapid development of necrotizing mediastinitis and inability to close the perforation surgically. To avoid leaks from the anastomosis the suture line can be buttressed with adjacent structures. The fundus of the stomach, parietal pleura and muscular flaps have been used to cover the perforation. We describe 2 patients with perforation of the lower esophagus. Both were operated on within 8 hours, the perforation was closed primarily and a diaphragmatic flap was formed to cover the suture line. There were no postoperative leaks and recovery was uneventful.


[Enteroperitoneal anastomosis for short bowel syndrome].

Creation of neomucosa is one of many experimental surgical techniques tried in order to improve the results of the complicated treatment of short bowel syndrome. The syndrome is associated with severe physical and mental retardation and not infrequently may be fatal. In this experimental study on pigs and rats we successfully enlarged the small bowel surface by growing new mucosa on the parietal peritoneum following enteroperitoneal anastomosis. The technique has 2 more important advantages: fluids and electrolytes are absorbed through the peritoneum and bowel transit time is slowed.


[Passive smoking: clinical aspects and workers' awareness].

Tobacco smoke contains a wide range of toxic vapors and particles which when inhaled are injurious both to the smoker himself (active smoking) and to those around him (passive smoking). It is extremely difficult to define precisely the harmful effects of passive smoking on the individual's health because of problems in quantifying the extent of exposure. A number of epidemiological studies indicate that exposure to passive smoking in public places is circumstantially, but marginally, linked to cardiovascular morbidity and mortality, as well as to pulmonary morbidity. both benign and malignant. Many clinical conditions are further aggravated by exposure to a combination of tobacco smoke and other industrial materials, including cadmium, and radon daughters. Passive smoking during pregnancy constitutes a health hazard for both mother and fetus. Exposure to passive smoking during childhood may predispose to benign and malignant pulmonary morbidity in adulthood. For many the workplace is the main site of exposure. In a pilot study during the past year on 1197 white and blue-collar workers, we found that the proportion of nonsmokers exposed to tobacco smoke at work is very high, almost 80%, and that workers are bothered by it. 2/3 are aware of the serious adverse health effects of tobacco smoke. 98% of the passive smokers and 75% of the active smokers considered legislation to limit smoking in public places justified.


[Effect of workload on physicians' drug prescribing].

The possible effect of workload on the prescribing of drugs by physicians was studied in 10 primary care pediatricians during a 1-month period. The intraphysician variability revealed a positive correlation (p less than 0.05) between workload and prescription of antibiotics in the case of 2 of the physicians and a negative correlation (p less than 0.05) between workload and prescription of all drug items in another physician. The prescribing of the other 7 was not affected by changes in daily workload. The interphysician variability study revealed a significantly increased rate of prescription of analgesics/antipyretics by physicians with increased monthly workload (r = 0.91, p less than 0.001). These results suggest that although the prescribing habits of a minority of physicians may be affected by their workloads, prescription rates remain stable for the individual physician on most occasions. However, physicians with high workloads tend to prescribe more analgesics/antipyretics than those with low workloads.


[Effects of oxiracetam on the decrease in population spikes in hypoxic and low glucose media].

Evoked potentials were recorded in rat cerebral cortical slices. The amplitude of the evoked potential was reduced by perfusion with hypoxic (0-25%) or low glucose (0-5 mM) media in a concentration-dependent manner, and the evoked potentials disappeared under severe conditions (below 15% O2, below 3 mM glucose). We investigated the protective effects of oxiracetam on the decrease in evoked potentials under hypoxic (15% O2) and low glucose (3 mM glucose) conditions. Drugs were perfused from 45 min before hypoxic or low glucose perfusion to the end of the experiment. Oxiracetam (10(-6)-10(-5) M) dose-dependently minimized the amplitude reduction of evoked potentials and prolonged their disappearance time. At a concentration of 10(-5) M, oxiracetam protected against the disappearance of evoked potential in 5 of the 6 samples under hypoxic conditions and in all 6 samples under low glucose conditions. Indeloxazine (5 x 10(-6)-10(-5) M) and bifemelane (5 x 10(-6)-10(-5) M) prevented the reduction of the amplitude of evoked potentials under low glucose conditions. However, these drugs had no effect at a concentration of 10(-6) M. These data indicate that oxiracetam has a protective effect against neuronal dysfunction and that this effect develops at a lower concentration than those of indeloxazine and bifemelane.


[Pharmacological effects of Gosha-jinki-gan-ryo extract: effects on experimental diabetes].

Pharmacological effects of Gosha-jinki-gan-ryo extract (KJE) on experimental diabetes induced by cyproheptadine (CPH), aldose reductase activity, and experimental peripheral neuropathy were studied. The effects of KJE were compared with those of Hachimi-jio-gan-ryo extract (HJE). KJE at 417 mg/kg/day (5 times the daily dose in humans) and HJE at 367 mg/kg/day (5 times the daily dose in humans) significantly inhibited the decrease in glucose tolerance by CPH. KJE and HJE inhibited aldose reductase activity, when DL-glyceraldehyde was used as substrate, with IC50 values of 2.68 x 10(-5) g/ml and 4.45 x 10(-5) g/ml, respectively and when D-glucose was used as substrate, with IC50 values of 1.04 x 10(-4) g/ml and 1.55 x 10(-4) g/ml, respectively. KJE at 209 mg/kg/day (2.5 times the daily dose in humans) and HJE at 367 mg/kg/day significantly reduced peripheral neuropathy induced by crushing the sciatic nerve in rats. The potency of these effects of KJE was stronger than that of HJE, when a comparison was made on the basis of the daily dose.


[Effects of mosapramine (Y-516), a new dopamine D2 antagonist, on reverse tolerance after repeated administration of methamphetamine by means of the ambulation-increasing effect in mice].

Effects of mosapramine (Y-516), a new dopamine D2 antagonist, on reverse tolerance (sensitization) after repeated administration of methamphetamine (MAP; 2 mg/kg, s.c.) were investigated by means of ambulatory activity in mice; and they were compared with those of clocapramine (CCP), bromperidol (BPD) and chlorpromazine (CPZ). Y-516 (0.3, 1, 3 and 10 mg/kg, p.o.), CCP (3, 10 and 30 mg/kg, p.o.), BPD (0.1, 0.3 and 1 mg/kg, p.o.), CPZ (1, 3 and 10 mg/kg, p.o.) or 0.5% methylcellulose (MC; solvent, p.o.) were given to mice 30 min before MAP administration. The ambulatory activity was measured by tilting-type activity changes for 3 hr after MAP. These treatments were repeated 5 times at 3-4 day intervals. Then MAP alone was challenge-administered to all of these mice 3-4 days after the final administration. Marked reverse tolerance was produced after repeated administration of MC plus MAP. On the other hand, the ambulation-increasing effect of MAP was suppressed dose-dependently in groups pretreated with Y-516 or comparison-drugs, although the development of reverse tolerance was not completely inhibited after the repeated administration. In the challenge-administration of MAP, the ambulation-increasing effect was dose-dependently suppressed in the Y-516 group or the comparison-drug plus MAP group as compared with that in the MC plus MAP group.


[Inhibitory effects of Hachimijiogan on micturition reflex via the locus coeruleus].

Pharmacological studies were undertaken to elucidate the role of Hachimijiogan in the micturition reflex via the locus coeruleus, using alpha-chloralose-anesthetized cats. Rhythmic contractions of the urinary bladder induced by continuous infusion of saline into the bladder were dose-dependently inhibited by intravenous injection of Hachimijiogan (10, 30 and 90 mg/kg), as well as flavoxate hydrochloride (1 and 3 mg/kg). In contrast, contraction of the urinary bladder elicited by electrical stimulation of the locus coeruleus was significantly suppressed by intravenous injection of flavoxate, but not affected by that of Hachimijiogan. These results suggest that Hachimijiogan acts on the afferent pathway from the urinary bladder to the locus coeruleus, thereby inhibiting the micturition reflex, while it has no effects on the efferent pathway from the locus coeruleus to the urinary bladder.


[Influences of hypercholesterolemia on the vessel function of isolated rat thoracic aorta].

Mature male rats (SD strain, 8-week-old) were fed with a normal diet or a high cholesterol diet (HC: 1.5% cholesterol and 0.5% Na cholate in the normal diet) up to 8 weeks, and we examined how the vascular function level of the isolated thoracic aorta and the histological figures of some tissues including the aorta would change. 1) The contracting reactivity to phenylephrine (Phe, 10 microM) and the relaxing reactivity to acetylcholine (1 microM) measured thereafter remained unchanged during the period of aging and were not influenced by HC-feeding. The addition of L-arginine (Arg, 100 microM) did not affect the results. 2) The ability of the aorta to release NO and to relax, which was evaluated as the extent of the endothelium-dependent potentiation by NG-monomethyl-L-arginine (NMA) of the Phe contraction, did not change by HC-feeding up to 4 weeks, but appears to be attenuated after 8-week feeding. 3) The EC50 of NMA for the potentiation estimated without the addition of Arg remained unchanged, while the one in the presence of Arg gradually increased with aging but not with HC-feeding. 4) The histopathological study of the aorta and other tissues failed to detect any notable atherogenic changes in any of the HC-fed groups. The results indicate that under the experimental conditions employed, HC-feeding would not develop any significant atherogenic histopathological changes in the endothelium-smooth muscle preparation, but may induce some dysfunction in the NO-release mediated and auto-regulatory function of the vascular tone.


Cell growth and alpha-amylase production characteristics of Bacillus subtilis.

Growth, differential rate of alpha-amylase synthesis and production characteristics of Bacillus subtilis DP 1 (isolate from starch materials) in comparison with 10 Bacillus strains were examined in batch fermentation. The effect of the carbon and nitrogen source was evaluated with regard to cell growth and enzyme production. The pH optimum of enzyme activity was 6.5 and temperature optimum of 60 degrees C.


Immunological quantification of RecA protein in cell extracts of E. coli after exposure to chemical mutagens or UV radiation.

Increased synthesis of RecA protein is induced in E. coli cells after their damage, the rate of synthesis being dependent on the extent of DNA alterations. The level of the RecA protein was determined in E. coli cell extracts after damage induced by NQO, MNNG, MMC, NAL or UV radiation, using competitive enzyme-linked immunosorbent assay (ELISA). Purified E. coli RecA protein and rabbit monospecific polyclonal antibodies against it were prepared for the quantitative assay. The level of the RecA protein was increased after treatment with all mutagens. Contrary to other induced proteins, the synthesis of the RecA protein increased within 30 min after damage with UV radiation at a relatively slow rate. The ELISA method made it possible to determine 0.5-50 ng of the RecA protein in bacterial extracts. The method can be employed as an auxiliary test for DNA damage determination and also in studied concerning the role of the RecA protein in repair processes.


Effect of growth rate on ethanol tolerance of Saccharomyces cerevisiae.

delta 5,7-Sterol-accumulating Saccharomyces cerevisiae cells growing in chemostat at a specific growth rate of 0.075/h exhibited higher ethanol tolerance measured as ethanol-induced death and anaerobic growth inhibition than the cells growing at 0.2/h, the difference being dependent on the carbon-to-nitrogen molar proportion in the medium. The observed difference in sensitivity to ethanol of anaerobic growth between the slowly and rapidly-growing cells was completely reversed as a result of a block in sterol synthesis causing a negligible synthesis of delta 5,7-sterols. Two physiological parameters, budding frequency and membrane composition, evidently affected ethanol tolerance. Differences between the delta 5,7-sterol-synthesizing and deficient strains documented a profound effect of the quality of the sterol present on the physiological state of the cell.


Biological effects of the antibiotic brefeldin A (decumbin, cyanein, ascotoxin, synergisidin): a retrospective.

Brefeldin A has been recently characterized to act as an inhibitor of intracellular protein export with profound effects on the structure and function of the Golgi apparatus in animal cells. Manifold activities of the antibiotic (under different names) published in the 1960's and 1970's are reviewed: effects on fungal growth and morphogenesis, inhibition of mitosis in plant cells, cytotoxicity, cancerostatic, antiviral and antinematodal activity and peculiar effects on DNA, RNA and protein synthesis in microbial and animal cells.


Effect of carbon and nitrogen sources on the production of penitrem B by Penicillium aurantiogriseum.

Effect of different carbon and nitrogen sources on the production of penitrem B was studied. D-Xylose induced maximum penitrem B production, while melibiose, glycerol, citric acid and succinic acid were poor substrates. Potassium nitrate, L-asparagine, sodium nitrate, glycine, DL-aspartic acid and L-tryptophan supported good production of penitrem B. Conversely zirconyl nitrate, barium nitrate, aluminum nitrate, acetanilide, 4-aminobenzoic acid, 4-nitrobenzoic acid and 4-nitroaniline were toxic and did not even permit the growth of the fungus.


Regulation of biosynthesis of vermiculin and vermistatin in Penicillium vermiculatum.

Biosynthesis of vermiculin (1) and vermistatin (2) in Penicillium vermiculatum can be controlled by the carbon and nitrogen sources. Glucose and sucrose affect the levels of the two metabolites; cornsteep liquor influences the quality the biosynthesis. The concentrations of Fe3+ and Cu2+ ions also affect the biosynthesis, the effect being dependent on the type of carbon source utilized. The compounds capable of electron transport generally stimulate the production of 1 and 2 but do not influence the biosynthesis qualitatively.


Effect of protein phosphorylation on the activity of RNA polymerase in streptomycetes.

RNA polymerase was isolated from Streptomyces granaticolor and protein kinase was partially purified from Streptomyces albus. When RNA polymerase was treated with protein kinase in vitro the activity of RNA polymerase was markedly enhanced. Furthermore, a protein of M = 65 kDa was isolated which, after being phosphorylated, stimulated RNA polymerase activity in vitro. Because neither the beta-subunits nor the alpha-subunits of RNA polymerase were phosphorylated it is assumed that phosphorylation of the 65 kDa protein may regulate the activity of RNA polymerase in streptomycetes.


Use of whey for production of exocellular polysaccharide by a mutant strain of Xanthomonas campestris.

Growth and kinetics of the production of exocellular polysaccharide was studied in a mutant strain of Xanthomonas campestris lac+ during cultivation in a submerged culture in a medium containing whey. The maximum production of the polymer was observed at the initial stage of the stationary growth phase of the culture. The mean production yield was about 1.4%. The results were comparable with those obtained during cultivation on a lactose medium.


Taxonomic studies of Streptomyces virginiae mutants overproducing virginiamycin M1.

By using both the traditional International Streptomycetes Project methods and chemical approaches followed by a hierarchical cluster analysis, Streptomyces virginiae mutants A-1 and B-43 (yielding higher amounts of the M1 component of virginiamycin complex), their wild ancestor ATCC 13161, and another virginiamycin producer, S. pristinaespiralis NRRL 2958, were subjected to taxonomic studies to find kinship or differences among the strains. Of the methods used, only the test of carbon utilization, investigation of spore surface and analysis of sugar constituents of cell walls proved to be reliable enough to demonstrate the species identity of S. virginiae strains and to distinguish them from S. pristinaespiralis. L,L-2,6-Diaminopimelic acid was present in all strains. Analysis of fatty acids and total proteins as well as investigations of morphology and pigmentation of agar cultures led to confusing results.


Characteristics of Streptomyces globisporus strain 0234A forming endospores in submerged cultures.

Thermosensitive submerged endospores formed by Streptomyces globisporus 0234 and its natural variant A resembled those of thermoresistant actinomycetes not only in their morphology ultrastructure, but also in the content of dipicolinic acid. The production of endospores containing this substance is unusual in Streptomyces while other features of the strain indicate relatedness to other streptomycetes. Chemotaxonomic analysis of variant A revealed the cell wall to be of chemotype I and fatty acid content typical of Streptomyces. Most characteristics of surface cultures of variant A coincided with those of the original strain 0234 and its endosporeless variant B. Both the strain 0234 and its variants A and B produced identical antibiotics and pesticidal compounds.


Degradation of the herbicide bromoxynil in Pseudomonas putida.

Biological conversion of the herbicide bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) was studied in a batch culture of Pseudomonas putida by using HPLC. The process had a cometabolic character and proceeded only in the presence of another, simultaneously metabolizable, carbon and energy source. The intensity of degradation correlated with the growth rate, the degradation stopping when the cosubstrate becomes exhausted or the pH value of the medium falls below 6.5. In a medium with glucose, no lag phase longer than one day was observed concerning growth, sugar and herbicide consumption and formation of metabolic herbicide derivatives (3,5-dibromo-4-hydroxybenzamide and 3,5-dibromo-4-hydroxybenzoic acid). In a medium with ribose, the initial lag of the above processes took 2 d. No formation of other degradation products was detected. Growth inhibition was proportional to the concentration of bromoxynil.


Effect of glucose and ribose on microbial degradation of the herbicide bromoxynil continuously added to soil.

Bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) was continuously added to chernozem (Haplic typic) soil inoculated with a suspension of Pseudomonas putida capable of cometabolic decomposition of the compound in a hetero-continuous-flow cultivation setup. In the steady state, when glucose or ribose were simultaneously added, 90 and 47% of the added herbicide was degraded per day, respectively. If the saccharides were absent, only 10-27% of the herbicide was decomposed. Addition and removal of glucose feeding resulted in an increase and decrease, respectively, of the degradation intensity, irrespective of the amount of the bacterial decomposers present. Two degradation products, 3,5-dibromo-4-hydroxy-benzamide and 3,5-dibromo-4-hydroxybenzoic acid, were formed during cultivation. The total amount of bromine-containing compounds was reduced only in the presence of glucose.


Phenomenological theory of substrate-induced acidification with application to Candida utilis dissimilating ethanol.

The mathematical theory of substrate-induced acidification by microorganisms was based on special formulation of mass and charge conservation laws for distinct species. The strength of the theory was tested on the ethanol-induced acidification by Candida utilis in pure water and in phthalate buffer. We showed that the theory may be used to approximate, extrapolate and predict the course of apparent acidification including the effects of buffering capacity of the broth. It makes it possible to formulate mathematical models that are suitable for process simulation and computer control of bioreactors when pH is used as a state variable.


Adherence of intestinal and extraintestinal Pseudomonas aeruginosa to tissue culture cells.

The adherence pattern of Pseudomonas aeruginosa strains to HeLa, Vero and CHO cells was studied. The diffuse type of adherence was found to prevail on HeLa cells. It was characteristic for intestinal and environmental strains. Urinary strains revealed more often a localized adherence. A similar pattern was obtained with CHO cells. Experiments with Vero cells showed an equal distribution of intestinal strains regarding the diffuse, localized and mixed adherence. Urinary strains revealed mostly a localized adherence of a similar pattern as was observed on HeLa and CHO cells.


Bacterial infection modulated by glucan: a search for the host defense potentiation mechanisms.

Interactions between bacteria and the host were studied from day 0 up to day 10 post-challenge in mice pretreated with soluble glucan (20 mg/kg i.p.) and challenged supralaryngeally with a virulent strain of Klebsiella pneumoniae. In the initial phase of infection, clearance of bacteria in the airways of glucan-treated mice was improved to an extent comparable with the vaccinated group but, in contrast to the immunized animals, subsequent regrowth of the bacterial inoculum was not prevented. The efficacy of defense, based during the entire course of infection mainly upon phagocytosis by neutrophils, markedly increased at intervals corresponding to the onset of humoral immune response. No evidence was obtained to indicate an enhanced involvement of alveolar macrophages in the phagocytosis of bacteria in glucan-stimulated mice. The results further support the notion that improvement of specific immune responsiveness rather than activation of nonspecific effector functions might be the most important expression of the host-defense-potentiating capacity of glucan and related stimulants of microbial origin.


Functional and metabolic changes of guinea pig peritoneal macrophages induced by bacterial vaccines.

Phagocytic activity of peritoneal macrophages of guinea pigs injected subcutaneously with bacterial vaccines was found to be increased. The phagocytic index remained unchanged or was decreased. In addition, a decreased candidacidal activity was observed. Metabolic activation of macrophages, measured by the INT test, was inhibited in unstimulated cells while cells stimulated with zymosan or opsonized zymosan exhibited higher values of the INT test as compared with control animals. After injection of vaccines the number of peritoneal macrophages was increased, but the spleen mass decreased.


Effect of pH on the stability of type-C toxin of Clostridium botulinum.

Stability of type-C botulinum toxin at pH 1.8-12.0 and during exposure to 5 and 28 degrees C for 20 and 16 h, respectively, was tested by titration on adult mice. The toxin was found in the samples kept at pH of 2.7-10.2, whereas, at the pH extremes of 1.8 and 12.0, it was inactivated.


Large-scale isolation and partial characterization of plasmid DNA from B. larvae.

Large-scale preparation of plasmid DNA from two Bacillus larvae strains 423 and 728, honey-bee pathogens, is described. The isolated plasmid DNAs were analyzed by restriction enzyme mapping. No difference in the resulting maps was found for six restriction enzymes. The plasmid DNAs were also compared by Southern blot hybridization and by electron microscopy. The results confirmed the identity of these plasmid DNAs. All these data suggest that B. larvae strains harbor the same plasmid.


Electron-microscopic study of the effect of various extractants on the morphology of Coxiella burnetii.

This paper presents the results of the effect of trichloroacetic acid (TCA) at two different temperatures and the effect of a mixture of detergents (D) on Coxiella burnetii. Both TCA and D caused a large destruction of C. burnetii cells. In both cases complexes of high-molar-mass components from the outer membrane were extracted. In the D case not only proteins but a mixture with other high-molar-mass structures were released from the destroyed cells. By extraction of TCA, the antigenic complex composed of lipopolysaccharides (LPS), proteins and phospholipids was released. The effect of the D mixture on C. burnetii causes their complete destruction. The TCA causes a surface destruction of cells but it does not cause complete disintegration. The small-cell variants (SCV) in both cases were shown to be more stable compared to the large-cell variants (LCV).


Growth and enzymological characteristics of a pink-pigmented facultative methylotroph Methylobacterium sp. MB1.

Growth characteristics of batch and continuous cultures of the pink facultative methylotroph Methylobacterium sp. MB1 were determined. The response of a chemostat culture to a pulse increase of methanol concentration was studied. Malate, succinate and oxaloacetate additions to the methanol-supplemented medium decreased batch culture growth inhibition by methanol. The carotenoid content in cells grown in a chemostat decreased with increasing growth rate. The key enzyme activities of C1-metabolism were measured in a chemostat culture at different dilution rates.


Cloning of Candida boidinii DNA fragments promoting autonomous replication of plasmids in Saccharomyces cerevisiae.

Fragments of Candida boidinii chromosomal DNA were inserted into the integrative vector YIp-kanr and examined for the presence of sequences promoting autonomous replication of plasmids in Saccharomyces cerevisiae. Restriction maps of two plasmids, designated S6/4 and S6/5, originating from the same S. cerevisiae transformant, were constructed. Southern hybridization data confirmed that the plasmids carry sequences from the C. boidinii chromosome. Both plasmids transform S. cerevisiae strains at 4-5-fold higher frequency than cloning vectors based on the replication origin of the 2 microns plasmid. Mitotic stability of the constructed plasmids is similar to that of the 2 mu-based vector pNF2 in S. cerevisiae.


Transformation of Streptomyces lincolnensis protoplasts with plasmid vectors.

A method for the preparation and regeneration of protoplasts of Streptomyces lincolnensis is described. Mycelium in the early exponential phase appeared to be most suitable for this purpose and yielded up to 25% regenerated intact cells. Transformation of S. lincolnensis protoplasts was achieved using broad-host-range streptomycete plasmid vectors pIJ622, pMP66, pRS410 and pIJ943 constructed from replicons pIJ101, pSLG33 and SCP2. The efficiency of transformation was 3.10(3) transformants per micrograms plasmid DNA when (2-5).10(7) recipient protoplasts were used. Interspecific transformations showed that there is no efficient restriction system in S. lincolnensis that would limit the transfer of genetic information from S. lividans or E. coli.


Comparison of permuted region lengths in the genomes of related Salmonella typhimurium phages P22 and L.

Lengths of permuted regions in the P22 and L phage genomes were estimated from the relative yields of DNA in many electrophoretic bands obtained using several restriction endonucleases. It was found that 3.6 kb (8.7%) of P22-DNA and 7.2 kb (17.8%) of L-DNA were circularly permuted. In both phages the sequential packaging process proceeded in the same direction and four headful-size DNA molecules were, on the average, cleaved in one packaging series. The differences in circular permutation may originate from different genome lengths because their average headful portions are very similar (42.5 kb in P22 and 42.3 kb in L).


Construction of a new Escherichia coli-Saccharomyces cerevisiae shuttle plasmid cloning vector allowing positive selection for cloned fragments.

A new E. coli-S. cerevisiae shuttle plasmid cloning vector (pPW263) with a positive type of selection, was constructed. The selection system, based on the regulatory region of lambda phage controlling the expression of tetracycline resistance, was derived from the cloning vector pUN121 (Nilsson et al. 1983). There are three cloning sites in the cI gene, EcoRI, HindIII and BglII, and, in addition, two unique sites in the neighborhood, BamHI and SalI. The size of the vector is 7.8 kb. The maintenance of the vector and the selection in yeast was ensured by the replication region of the 2 mu plasmid and by the URA3 marker gene, respectively.


Purification of the cellulase complex produced by Penicillium camemberti and its partial characterization.

Three cellulase components (FP-ase, CMC-ase and cellobiase) were purified by affinity binding on Avicel followed by Sephadex G-25, DEAE-Sepharose, DEAE-cellulose and Sephadex G-100 chromatography from the culture filtrate of the newly isolated strain Penicillium camemberti. The isolated enzymes had the properties of cellobiohydrolase, endo-1,4-beta-D-glucanase and cellobiase and their respective molar masses were 99, 87 and 61 kDa as determined by molecular sieve chromatography on Sephadex G-100. The amino acid composition of each fraction was also determined.


Purification and kinetics of extracellular phospholipase A of Salmonella newport.

Attempts were made to purify and study the kinetics of extracellular phospholipase A of Salmonella newport (6,8, eb; 1,2). The enzyme was purified by salt precipitation followed by gel filtration, using different grades of Sephadex. The enzymically active purified preparation was found to be a protein, having molar mass ranging between 43 and 67 kDa. The enzyme had a pH optimum at 7.5, giving 18.2 micrograms of lysophosphatidylcholine per mg protein. Its activity was enhanced by all metal ions except potassium, by solvents and surfactants except sodium dodecyl sulfate. It hydrolyzed the membrane phospholipids of red blood cells and was inhibitory to the growth of other microorganisms.


Construction and use of Agrobacterium tumefaciens binary vectors with A. tumefaciens C58 T-DNA genes.

Five plant morphoregulatory genes were isolated from the Agrobacterium tumefaciens Ti plasmid and binary plasmid vectors for plant transformation with these genes were constructed. All vectors have a similar structure with T-DNA borders, RK2 origin of replication and chimeric kanamycin resistance gene for the selection of transformed plant tissues. Over twenty vectors with single and combined morphoregulatory genes were constructed and their effects after tobacco tissue transformation studied.


Viability of basidiospores of Agrocybe cylindracea and Oudemansiella mucida and antibiotic activity of monosporic isolates in the course of 15 years of storage.

Basidiospores of Agrocybe cylindracea were found to be viable for 12 years, those of Oudemansiella mucida for 6 years. The ability of monosporic isolates from these spores to produce antibiotics has been partly preserved.


Screening for a new generation of anthelminthic compounds. In vitro selection of the nematode Caenorhabditis elegans for ivermectin resistance.

Development of resistance to ivermectin in vitro is reported for the first time. Two strains of Caenorhabditis elegans D5 and D6 able to grow on agar plates after treating with up to 3 mg ivermectin per L were selected. The parent strain N2 was extremely sensitive to ivermectin, its growth being inhibited by treatment with 0.1-0.2 mg IVM per L.


Restorative resection for cancer of the rectum.

The importance of sphincter preservation in the surgical treatment of rectal cancer was emphasized more than a century ago. Combining these techniques with adequate anterior resection has permitted restorative resection in the treatment of most rectal cancers. Miles' abdominoperineal resection is now being used much less frequently. In this review, the pertinent technical factors, patient selection and current issues relevant to restorative resection of the rectum are presented.


Coloanal anastomosis following low anterior resection.

Low anterior resection with coloanal reconstruction is indicated for rectal cancer when APR is not necessary and conventional LAR is not possible. LAR/CAA, in properly selected patients, yields results equivalent to those achieved with APR, since it encompasses equally the primary routes for regional spread. Most patients with midrectal tumors are candidates for LAR/CAA if an intrapelvic anastomosis is technically impossible. Complete dissection of the rectum and its mesentery to the anal hiatus of the pelvic diaphragm is essential for optimal cancer treatment and appropriate selection of cases for sphincter preservation. Careful attention to five technical points are essential for a successful outcome with respect to survival and function: (1) complete mobilization of the left colon; (2) sharp dissection; (3) restoration of the anorectal right angle and complete sacralization of the transposed colonic segment; (4) meticulous pelvic hemostasis and drainage to avoid septic complications; (5) routine use of diverting colostomy until completion of healing. In the long run, the LAR/CAA offers patients good function with few side effects and is universally preferable to a permanent colostomy. By avoiding permanent colostomy, cancer treatment is improved without compromising survival.


Abdominosacral resection for midrectal cancer.

Abdominosacral resection is the most reliable radical sphincter-saving operation for midrectal cancers which are too low for anterior resection. The posterior incision provides maximum exposure for wide resection of the tumor, a measured distal margin, and an accurate anastomosis. The procedure can be carried out consistently to the pelvic floor without disrupting the anal sphincters and their innervation. Sphincter function is consistently preserved. Mortality rate is no higher than for other radical rectal resections. Morbidity can be limited by the selective use of protective colostomy. The use of mechanical retractors and the end-to-end stapler facilitates the operation and should encourage its wider application. The transsacral approach allows mobilization of the rectum to the levators in every case, and resection is limited only by the distance of the tumor from the sphincter, and not by poor exposure due to obesity or a narrow pelvis. In the treatment of 926 consecutive patients with rectal cancer, sphincter-saving resection was possible in 79%. In our experience, abdominosacral resection extends the range of sphincter-saving resection beyond that which is possible by the abdominal approach alone, with no compromise in safety and no increased risk of local recurrence or death from cancer.


Local excision of early rectal cancer.

During the past 15 years, data from numerous multimodality trials have shown significant improvement in outlook for patients with "high risk" colon and rectum cancers. In this paper, a suggested next step is to use the advance in multiple treatment approach to challenge the major toxicity of treatment in patients with rectum cancer--the permanent colostomy.


Adjuvant therapy in rectal cancer.

Local failure in the pelvis following radical surgery for rectal cancer produces severe morbidity and responds poorly to subsequent therapy. Overall, 25% of rectal cancer patients will recur in the pelvis. The use of adjuvant pelvic radiation therapy combined with systemic chemotherapy is effective in reducing the incidence of local recurrence as well as subsequent distant metastases. Current clinical trials are evaluating various radiation-chemotherapy-surgical interactions as well as the most efficacious chemotherapy program.


Prognostic significance of ploidy determination in rectal cancer.

Between 1965 and 1981, 154 patients with potentially curable rectal adenocarcinoma underwent surgical treatment at the University of Chicago Medical Center. In 134 cases, enough histological material was available to perform determinations of DNA content by the cytophotometric method (n = 108), or by the flow cytometric technique (n = 109). In 83 cases, DNA content was analyzed in the same specimen with both techniques, and in 77 of these cases the sections obtained from the paraffin blocks were contiguous. When using flow cytometry, 62% of stage B and 74% of stage C lesions were classified as aneuploid on the basis of a DNA index greater than 1. This correlation was statistically significant (p = 0.002). Patients with diploid tumors had an actuarial five-year survival equal to 62% in comparison with a 46-51% five-year survival for patients with aneuploid tumors. This difference was not statistically significant and it was explained by the tendency for aneuploid tumors to be in an advanced histopathological stage.


Morbidity and mortality after surgical resection of liver tumors. Analysis of 229 cases.

Two hundred and twenty-nine resections of hepatic tumors were performed over the past 10 years. The intraoperative death rate, 30-day operative mortality and major complication rate were 1.3%, 8.3% and 20%, respectively. Both morbidity and mortality were significantly related to the type of surgery and to the extent of the resection to contiguous organs and/or structures. Cirrhotic patients (40% in hepatocellular carcinoma) had a higher mortality rate (19%). Intraoperative blood loss was related to the extent of the resection and was significantly higher in patients with major complications and/or death. The main problem was postoperative liver failure in cirrhotic patients, which is difficult to predict and to treat.