Effect of different glass ionomers on the acid production and electrolyte metabolism of Streptococcus mutans Ingbritt.

In order to study the effects of different glass ionomers on the metabolism of Streptococcus mutans, test slabs of freshly mixed conventional glass ionomer (Fuji), silver glass ionomer (Ketac-Silver), composite (Silux), and 2-week-old Fuji were fitted into the bottom of a test tube. A plaque-like layer of S. mutans strain Ingbritt was centrifuged onto the test slabs, and the samples were incubated for 20 h in 1.7% (w/v) sucrose solution. For freshly mixed Fuji and Ketac-Silver, the pH fall was significantly smaller than for old Fuji and composite. These materials also released the largest amount of fluoride into the fluid phase. Incubation with glass ionomer materials led to an increase in the cellular concentration of fluoride in bacteria, but intracellular fluoride did not correlate with the fall in pH. The lowest pH was associated with the lowest cellular magnesium content. Ketac-Silver released large amounts of calcium in the fluid phase, and the cellular calcium content was doubled in this group. The results show that freshly mixed glass ionomers affect acid production and electrolyte metabolism of S. mutans in vitro. The effect of conventional glass ionomer, however, seems to disappear after a few weeks. The effects of calcium and silver released by cermet glass ionomer deserve further study.


Oral sugar clearance and root caries prevalence in rheumatic patients with dry mouth symptoms.

The relationship between root caries, oral sugar clearance, salivary flow rate, and salivary counts of mutans streptococci, lactobacilli and candida has been studied in a group of 22 rheumatic patients (age range 40-72 years). The study group comprised all subjects volunteering for a clinical trial on relief of dry mouth symptoms. The median salivary flow was 0.09 ml/min at rest and 0.9 ml/min during chewing stimulation. The median sugar clearance time was about 5 min in the sublingual area and 16 min in the lower buccal vestibule. For subjects with 0-2 root caries lesions the clearance time at both sites was shorter than for subjects with 3 or more lesions (p < 0.05). A long oral clearance time was significantly correlated with age, root caries (DS and DFS), low resting salivary flow, and high salivary counts of mutans streptococci. It is concluded that root caries in rheumatic patients with low salivary flow is significantly related to oral sugar clearance time.


Validity of probing for fissure caries diagnosis.

One hundred extracted molar teeth with discoloured fissures but without any visible carious cavitation were selected from a large supply, using standardized criteria. The teeth were mounted, placed on a mechanical balance, and probed with a force of 500 g in every fissure, at as many places as possible. Every time the probe was found to stick, the spot was marked. After probing colour slides were made of the occlusal faces. Subsequently, the crowns were embedded in epoxy resin. 700 microns thick sections were cut in a facial-lingual direction with a diamond wheel. From the sections X-rays were taken which were scored as follows: a measuring grid was placed on the X-ray image of a section, and the caries score (0-4) for every millimetre was determined. By scoring every section of a tooth in this way, an overview was obtained of the location of all caries lesions in the occlusal surface. By comparing this overview with the colour slide of the tooth, the relationship between the sticky spots and the lesions was visualized. The results indicate that only 24% of the caries lesions were discovered by probing for stickiness (low sensitivity), but that the probe seldom stuck in a sound fissure (high specificity, > 99%). Probing proved to be unreliable for the diagnosis of fissure caries.


Prediction of root caries in periodontally treated patients maintained with different fluoride programmes.

The aims of the investigation were to evaluate the effect of different fluoride programmes, as adjuncts to professional plaque control every 3-4 months, on root caries incidence in periodontally treated patients and to identify risk factors for root caries development. Ninety-nine individuals, 33-76 years old, who had been treated for periodontal disease were subjected to one of three fluoride programmes during a 2-year period: (1) professional application, 3-4 times/year, of Duraphat (n = 34) or (2) of a 0.4% stannous fluoride gel (n = 33), or (3) daily mouthrinsing with a 0.05% sodium fluoride solution (n = 32). A number of clinical recordings and laboratory tests, used as presumptive risk indicators for root caries, were carried out before and on three different occasions after the periodontal treatment. No statistically significant differences were found between the various fluoride programmes. During the 2-year period, a total of 246 new decayed or filled surfaces (DFS) were recorded, 72 (29.3%) of which were diagnosed as active and 124 (50.4%) as inactive root caries lesions; 50 (20.3%) of the surfaces had been restored. Individuals with > or = 1 new root DFS during the 2 years (n = 50) differed significantly from those with 0 new root DFS (n = 49) as concerns salivary counts of mutans streptococci and lactobacilli, root plaque scores and percentage of exposed root surfaces. Baseline root caries prevalence (r = 0.43) and root plaque scores (r = 0.36) showed the highest correlations with new root DFS.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevalence and intraoral distribution of coronal and root caries in middle-aged and older adults.

This work describes the prevalence and intraoral distribution of coronal and root caries in 326 predominantly white, educated, middle-aged and older adults. Study participants were recruited from Tufts Geriatric Outreach Program, Nutritional Status Study (NSS), and the Forsyth Root Caries Study. Eighty-five percent of participants reported visiting their dentist in the last year. The median number of teeth was 21 in the 65+ age-group, and 40% of participants had coronal caries and 33% had root carious lesions. The mean coronal and root caries (DFS) was higher and the proportion of decayed surfaces to all decayed and filled surfaces (%D/DFS) was lower than in other comparable studies. A comparative analysis of intraoral distribution of coronal and root caries and their relation with age is discussed.


Time trends in caries experience of children in England and Wales.

Regular national surveys of child and adult dental health and regionally coordinated surveys of caries experience in children provide a comprehensive picture of secular changes in disease levels in England and Wales. The substantial decrease in mean dmft in 5-year-olds between 1973 and 1983, amounting to 7.7% per annum, slowed to 0.9% per annum between 1983 and 1989/90. Conversely the decline in DMFT in older children and adolescents has accelerated more than twofold since 1983. In some parts of the country, caries experience at 5 years has shown a small increase and possible reasons for this are discussed. The validity of the survey data is examined and ways of consolidating and maintaining the downward trend in disease are considered.


[The importance of detection of antigliadin antibodies in the diagnosis and therapy of celiac disease in children].

The authors describe the method of assessment of antigliadin antibodies class IgA and IgG by the ELISA method. In a group of children with untreated coeliac disease the antigliadin antibodies were elevated in 91.6%, in a group of children with coeliac disease after exposure to gluten in 87.8%, in children on a gluten-free regime in 48.5%. The dynamics of antigliadin antibodies in the course of the first year are presented--their decline in serum of children suffering from acute coeliac disease after elimination of gluten and conversely their rise after discontinuation of the gluten-free diet in children previously treated for prolonged periods. The sensitivity of the assessment is 91.6% and the specificity 90.6%.


[The effect of breast feeding on morbidity in children].

The authors investigated in a group of 4210 children from birth to three years from Southern Moravia the morbidity from respiratory infections, diarrhoea and other infections. There were bisexual differences in morbidity, girls were less frequently ill. Children from child communities had a two old morbidity. Birth order was also important. The influence of natural nutrition was apparent in particular during the first year when infants breastfed for more than 4 months had significantly fewer spells of illness. These results were influenced by sex and birth order. At the age of two and three years the differences between children breastfed for a short and long time disappeared. Similar results were found also in other morbidity indicators such as administration of antibiotics, number of hospital admissions and mean number of days spent in hospital.


[Morbidity in children up to 1 year of age and factors affecting it during a longitudinal prospective study].

During a longitudinal survey of 5154 children under one year the morbidity was investigated and the influence of some psychosocial, socioeconomic and oecological factors which influence morbidity. These are partial results of a long-term research project.


[Intraosseous infusions in children].

The authors submit a review on th intraosseous approach to infusions and their possible application in emergency medicine.


[ACE inhibitors--a prospective new group of drugs for the treatment of kidney diseases].

ACE inhibitors which till recently were used only in the treatment of cardiovascular diseases are becoming a perspective group of drugs also in the treatment of chronic nephropathies. It was revealed that they are effective in particular in the treatment of proteinuria of different etiology and have also a marked renoprotective effect and are therefore recommended to slow down the progression of renal failure. They reduce intraglomerular hypertension, increase glomerular filtration and the renal blood flow, and it is assumed that they can retard the progression of chronic glomerulonephritis and diabetic nephropathy. It may be excepted that their therapeutic application will in the near future be extended also to clinical nephrology.


Constituents of the roots of Cynanchum bungei Decne. Isolation and structures of four new glucosides, bungeiside-A, -B, -C, and -D.

Four new glucosides, bungeiside-A, -B, -C, and -D, were isolated from the roots of Cynanchum bungei Decne. The structures of the new compounds were determined by chemical and spectroscopic methods, including two-dimensional nuclear magnetic resonance (2D NMR) techniques, especially 1H-detected heteronuclear multiple-bond multiple-quantum coherence.


Resin glycosides. XV. Simonins I-V, ether-soluble resin glycosides (jalapins) from the roots of Ipomoea batatas (cv. Simon).

Five new ether-soluble resin glycosides (jalapins), simonins I-V, have been isolated from the roots of Ipomoea batatas and characterized on the bases of chemical and spectral data. Simonin I is the first example of resin glycoside with aromatic acid (trans-cinnamic acid) as a component organic acid.


Repandiol, a new cytotoxic diepoxide from the mushrooms Hydnum repandum and H. repandum var. album.

Repandiol, a new cytotoxic diepoxide has been isolated from the mushrooms Hydnum repandum and H. repandum var. album. The chemical structure was elucidated as (2R,3R,8R,9R)-4,6-decadiyne-2,3:8,9-diepoxy-1,10-diol on the basis of spectroscopic analysis. The structure was confirmed by the synthesis of optically active repandiol. Repandiol displayed potent cytotoxic activity against various tumor cells.


Russuphelin A, a new cytotoxic substance from the mushroom Russula subnigricans Hongo.

A new cytotoxic substance, designated russuphelin A (1), has been isolated from the mushroom Russula subnigricans Hongo (Basidiomycetes). The structure was elucidated as 2,6-bis(2,6-dichloro-4-hydroxyphenyloxy)-1,4-dimethoxy-benzene on the basis of spectroscopic data and confirmed by total synthesis.


5-Lipoxygenase inhibitors isolated from the mushroom Boletopsis leucomelas (Pers.) Fayod.

Terphenyl compounds, tentatively named Bl-I (1), Bl-II (2), Bl-III (3), Bl-IV (4) and Bl-V (5), showing 5-lipoxygenase inhibitory activity have been isolated from the mushroom Boletopsis leucomelas (Pers.) Fayod. On the basis of physico-chemical and spectral evidence, they were concluded to be a series of cycloleucomelone-leucoacetates.


Studies on antiplatelet agents. I. Synthesis and platelet inhibitory activity of 5-alkyl-2-aryl-4-pyridylimidazoles.

5-Alkyl-2-aryl-4-pyridylimidazoles were synthesized and tested in rat ex vivo platelet aggregation studies. Among these compounds, 2-(2-fluorophenyl)-5-methyl-4-(3-pyridyl)imidazole (25) was most potent, and showed 98% inhibition at a dose of 10 mg/kg (p.o.). 25 had inhibitory activity on cyclooxygenase, thromboxane A2 (TXA2) synthetase, and phosphodiesterase, and also showed inhibited KCl-induced contraction of rat aorta. All compounds have little acute toxicity and appear to be free of adverse effects on the stomach.


Renin inhibitors. II. Synthesis and structure-activity relationships of N-terminus modified inhibitors containing a homostatine analogue.

The synthesis and structure-activity relationships of N-terminus modified renin inhibitors containing the homostatin analogue, (2RS,4S,5S)-5-amino-2-ethyl-4-hydroxy-7-methyloctanoic acid, are described. The compounds having a 3-alkyl (or aryl)sulfonylpropionyl residue at the N-terminus are found to be potent inhibitors which contain two amino acids. (2RS,4S,5S)-N-Isobutyl-5-[N-[(2S)-3-ethylsulfonyl-2-(1- naphthylmethyl)propionyl]-L-norleucyl]-amino-2-ethyl-4-hydroxy-7- methyloctanamide (20) has an IC50 of 0.5 nM against human plasma renin and the oral bioavailability of 20 is 0.73% in rats. Interaction between renin and the N-terminus of 1 and 20 is discussed in molecular modeling studies.


Stability in aqueous solution of two monocyclic beta-lactam antibiotics: aztreonam and nocardicin A.

The catalytic effect of various buffer systems (citrates, acetates, phosphates, borates and carbonates) on the degradation of aztreonam and nocardicin A in aqueous solution was studied at 35 degrees C and a constant ionic strength of 0.5 mol.dm-3 over a pH range of 3.50 to 10.50. The observed degradation rates, obtained by measuring the remaining intact antibiotic, were shown to follow pseudo-first-order kinetics with regard to antibiotic concentrations and to be influenced by general acid and general base catalysis. The changes in the concentration of intact beta-lactam antibiotic in the solutions were established by reverse-phase HPLC with UV-detection. In general the buffer systems employed in the kinetic studies showed a very weak catalytic effect on the degradation of aztreonam and nocardicin A. The pH-rate profiles for these antibiotics showed degradation minimums at pH 5.38 and 6.13, respectively. Aztreonam is slightly more reactive with hydrogen ions than nocardicin A and is much more reactive with hydroxide ions. In comparison with other beta-lactamic antibiotics, aztreonam and nocardicin A are much more stable in aqueous solution, except for aztreonam in a base solution, which is just as unstable as penicillins and cephalosporins. The Arrhenius activation energies were determined for aztreonam and nocardicin A at pH's 4.23, 6.59 and 8.60.


Catalysis of hydrolysis and aminolysis of non-classical beta-lactam antibiotics by metal ions and metal chelates.

The Zn(2+)-tris (hydroxymethyl)aminomethane (Tris) system has a great catalytic effect on the hydrolysis and aminolysis of some beta-lactam antibiotics. In order to ascertain the mechanism of this catalysis we have analysed the effects of the beta-lactam antibiotic structure. First we studied the kinetics of the decomposition of imipenem, SCH 29482, aztreonam and nocardicin A in aqueous solution of Tris at 35.0 degrees C, 0.5 mol.dm-3 ionic strength and in the presence of metal ions (Zn2+, Cd2+, Co2+, Cu2+, Ni2+ and Mn2+). From these studies, we conclude that Tris and metal ions (in separate solutions) exert a great catalytic effect on the hydrolysis of imipenem and SCH 29482. We suggest that in metal ion solutions a 1:1 complex is formed between the metal ion and beta-lactam antibiotic, which is attacked by hydroxide ions. Studies of the degradation of the antibiotics studied in solutions of Tris and metal ions together indicate that the systems Cd(2+)-Tris and Zn(2+)-Tris have a great catalytic effect on the hydrolysis and aminolysis of imipenem and SCH 29482. We suggest that this catalysis takes place via a ternary complex in which the metal ion plays a double role by (a) placing the antibiotic and the Tris in the right position for the reaction and (b) lowering the pKa of the hydroxide group of Tris, which is coordinated with the metal ion, generating a strong nucleophile.


Nematocidal activity of long alkyl chain amides, amines, and their derivatives on dog roundworm larvae.

The nematocidal activity of amides and amines having a long alkyl chain against the second-stage larva of dog roundworm, Toxocara canis, was examined. Long chain acyl amides with smaller substituents on the nitrogen showed stronger activity and the activity of cyclic amine amides was stronger than that of acyclic ones. In a series of homologous amides, the activity was dependent on the alkyl chain length: it reached a maximum at an optimal chain length and decreased in both shorter and longer homologues. The relationship between the activity and hydrophobicity of the homologues was analysed by the use of the bilinear model. The hydrophobicity of a compound, which gives a maximal activity, was similar for all neutral amides, but amides which have an additional amine group in the molecule had different values. Tertiary amines and their salts having a long alkyl chain also showed nematocidal activities comparable to those of the corresponding amides. The salts killed the larva at concentrations lower than their critical micell concentration, suggesting that they behave as a single molecule for the nematocidal action.


New bronchodilators. II. 3H-imidazo[4,5-c]quinolin-4(5H)-ones.

A series of novel 3-substituted imidazo[4,5-c]quinolin-4(5H)-ones (2a-w) was prepared by the reaction of imidazo[4,5-c]quinolin-4(5H)-ones (6) with several electrophiles under basic conditions. The bronchodilatory activity of these compounds was evaluated on the basis of their protective effects against antigen-induced contraction (the Schultz-Dale reaction) of guinea-pig trachea (in vitro) and antigen inhalation-induced bronchospasm in passively sensitized guinea-pigs (in vivo). Although correlations between in vitro and in vivo activities were not clear, short alkyl chains such as the methyl and ethyl groups at the 3-position were important for potent activity, especially in vivo. Substituents at the 5-position were more tolerant of the activity than those at the 3-position. 5-Ethyl-3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one (21) exhibits the most potent bronchodilatory activity among our tested compounds and is at least 5-fold more active than theophylline in vivo.


Amino acids and peptides. XVI. Synthesis of N-terminal tetrapeptide analogs of fibrin alpha-chain and their inhibitory effects on fibrinogen/thrombin clotting.

N-Terminal tetrapeptide analogs of fibrin alpha-chain were synthesized by the solution method using a new active ester, the ester of the oxime of p-nitroacetophenone, and by the solid-phase method. Their inhibitory effects on fibrinogen/thrombin clotting were examined. Of the synthetic peptides, amide analogs of Gly-Pro-Arg-Pro exhibited a more potent inhibitory effect.


The reactions of beta- and alpha-pyranose peracetates with PCl5, and utilization of the products to construct sarsasapogenin glycosides.

The reactions of beta- and alpha-pyranose peracetates with PCl5 gave products regioselectively chlorinated. The reactions of 1,2,3,4,6-penta-O-acetyl-beta-D-glucopyranose (5) and -beta-D-galactopyranose (6) with PCl5 in CCl4 and that of methyl 2,3,4-tri-O-acetyl-beta-D-glucuronatopyranose (7) with PCl5 in toluene gave 2-O-trichloroacetyl-beta-D-pyranosyl chlorides 4, 12 and 14, respectively, as major products, and alpha-D-pyranosyl chlorides 11, 13 and 15, respectively, as minor products. On the other hand, the reactions of compounds 8 and 9 which were alpha-anomers of 5 and 6, respectively, with PCl5 gave as major products transformed acetyl groups at C-6 to -C(Cl) = CCl2 or -C(Cl)2-CCl3 group (16 and 17 from 8 and 18 from 9). The same reaction of 10, which was alpha-anomer of 7, gave alpha-chloride 15 as a major product. The glycosidation of sugar derivative 4 with sarsasapogenin 23 gave beta-glycoside 24 (29.1%) and alpha-glycoside 25 (46.9%), and that of 12 with 23 gave beta-glycoside 26 (24.0%) and alpha-glycoside 27 (40.8%). The improvement of the yields of beta-glycosides 24 and 26 (66.9 and 62.1% for 24 and 26, respectively) in the glycosidations were accomplished by the employment of alpha-bromides 28 and 29 obtained from 4 and 6, respectively. The glycosidations of monoglycosides 30 and 31 obtained by the treatment 24 and 26, respectively, with ammonia-saturated ether with sugar acetate bromides 32 and 34 gave diglycoside derivatives 35 and 33, respectively.


Six new triterpenoidal glycosides including two new sapogenols from Albizziae Cortex. V.

Six new triterpenoid glycosides called julibrosides A1-A4, B1 and C1 were isolated from Albizziae Cortex, the dried stem bark of Albizzia julibrissin Durazz. Their structures were determined based on spectral and chemical evidence. Julibrosides B1 and C1 had new sapogenols, designated julibrogenin B and C, respectively, while julibrosides A3 included N-acetyl-D-glucosamine as a sugar component.


Isolation and identification of a cytotoxic principle from Chrysosplenium grayanum Maxim. (Saxifragaceae) and its antitumor activities.

A cytotoxic principle was newly isolated from Chrysosplenium grayanum Maxim. (Saxifragaceae) and identified as beta-peltoboykinolic acid (1) on the basis of spectral data. Cytotoxicity of compound 1 was tested against various human cancer cell lines in vitro, and antitumor effect of this compound was demonstrated on Meth.A mouse fibrosarcoma. The experiment of combined treatment with compound 1, mitomycin C, and OK-432 resulted in enhancing the antitumor effect against B16-BL6 mouse melanoma in C57BL/6 mice.


Nucleotide sequences of membrane-bound hydrogenase gene in Alcaligenes hydrogenophilus.

The nucleotide sequences of membrane-bound hydrogenase small (hupS) and large (hupL) subunit genes of hydrogen bacterium Alcaligenes hydrogenophilus were determined. The hupS and hupL genes encoded polypeptides of 363 and 619 amino acids, respectively. The hupS was located upstream of hupL with 35bp of intergenic region. The consensus ribosome-binding sequences were identified upstream of the start codons of hupS and hupL. Amino acid sequence of hupS is very similar to that of Rhodobacter capsulatus, Bradyrhizobium japonicum, and Azotobacter vinelandii at amino acid levels of 82%, 77%, and 81%, respectively. Similarly, amino acid sequence of HupL is similar to that of R. capsulatus, B. japonicum, and A. vinelandii at amino acid levels of 63%, 65%, and 68%, respectively. Northern hybridization analysis showed that hupS and hupL were co-transcribed, and addition of fructose to the culture medium remarkably decreased the amount of mRNA transcribed from hupS and hupL.


Bioavailability study of commercial sustained-release preparations of diclofenac sodium in gastrointestinal physiology regulated-dogs.

The gastrointestinal (GI) physiology of beagle dogs was regulated with a combined-treatment of intramuscular pentagastrin (10 micrograms/kg x 2) and intravenous atropine sulfate (0.02 mg/kg x 1). Here, the gastric acidity, the gastric emptying time and the small intestinal transit time in the regulated-dogs were respectively around pH 2, 0.7h and 4h, approximating those in healthy humans. The superiority of the regulated-dogs over the intact dogs was confirmed in comparative bioavailability studies by using two classes of commercial preparations. Both the conventional tablet and the sustained-release capsule of diclofenac sodium exhibited simple and similar average plasma concentration-time curves of free diclofenac in the intact dogs, while the latter preparation is reported to reveal a bimodal plasma curve of the drug in healthy humans. The regulated-dogs, however, permitted a bimodal average plasma pattern of the drug for the capsules due to an approximation of the GI physiology between humans and these classes of the dogs. The combined-treatment of beagle dogs with pentagastrin and atropine sulfate seems to supply a useful animal model in predicting the absorption characteristics of the sustained-release preparations and poor water-soluble drugs.


Inhibition of apical membrane enzyme activities and protein synthesis by gentamicin in a kidney epithelial cell line LLC-PK1.

The mechanism of a gentamicin-induced decrease in apical membrane enzyme activities was investigated in LLC-PK1 cells. Increasing activities of apical membrane enzymes (alkaline phosphatase, aminopeptidase, and gamma-glutamyltransferase) were markedly suppressed by gentamicin during growth in culture. On the other hand, a lesser effect was observed when the activities of these enzymes were decreasing or relatively constant. Gentamicin treatment decreased the maximal enzyme activities of alkaline phosphatase and aminopeptidase, indicating that the number of active enzyme molecules in the apical membrane was decreased by gentamicin. [3H]Leucine incorporation in LLC-PK1 cells was inhibited by gentamicin in a dose-dependent manner, followed by a reduction of total protein. In addition, a well-known protein synthesis inhibitor, cycloheximide, also decreased the apical enzyme activities. These results suggest that the inhibition of protein synthesis by gentamicin is a possible cause of the decreased activities of apical membrane enzymes in LLC-PK1 cells. The inhibition of protein synthesis may be related to the nephrotoxicity induced by aminoglycoside antibiotics.


Thyroxine binding properties of glycosylated bovine serum albumin.

Thyroid hormone, thyroxine (T4) binding properties of glycosylated bovine serum albumin (G-BSA), and intact BSA were studied by the fluorescence method. The apparent binding constants for intact BSA were 0.8 (0.16) x 10(6) M-1 at pH 5.0 and 2.18 (0.06) x 10(6) M-1 at pH 9.5 at 25 degrees C. T4 binding for G-BSA was independent of pH and the apparent binding constant was 1.4 x 10(6) M-1. Thermodynamic parameters were also evaluated from the Van't Hoff plots of the apparent binding constants at pH 7.4 and 8.5. At both pH's, the free energy, enthalpy and entropy changes were almost the same for both G-BSA and BSA.


Triterpene glycosides from the seeds of Astragalus sinicus L.

From the seeds of Astragalus sinicus L. (Leguminosae), seven triterpene glycosides were isolated and identified as soyasaponin I-III methyl esters (1-3) which were treated with CH2N2 during the separation procedure, soyasaponin IV (4), soyasapogenol B 3-O-beta-D-glucuronopyranoside (5), 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-xylopyranosyl(1-->2)-beta-D- glucuronopyranosyl 3 beta, 22 beta, 24-trihydroxy-11-oxoolean-12-ene (6), whose sapogenol (8) was obtained by enzymatic hydrolysis using glycyrrhizinic acid hydrolase, unambiguously characterized and designated as complogenin, and 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D - glucuronopyranosyl complogenin (7).


A new metabolite of 2,4,3',4'-tetrachlorobiphenyl in rat feces.

Metabolism in vivo of 2,4,3',4'-tetrachlorobiphenyl (TCB) was further studied using male Wistar rats. When the extract of feces of rats given TCB with chloroform was methylated and applied to gas chromatography (GC)-mass spectrometry (MS), a new metabolite was detected. The structure of this new metabolite was 4-hydroxy-2,5,3'4'-TCB based on both its retention time in GC and comparison of the mass spectrum with that of the synthetic sample. 4-Hydroxy-2,5,3',4'-TCB was assumed to be formed via a 4,5-oxide intermediate followed by NIH-shift of a chlorine atom at 4-position.


Gastric emptying rate of drug preparations. III. Effects of size of enteric micro-capsules with mean diameters ranging from 0.1 to 1.1 mm in man.

The gastric emptying rates of three enteric micro-capsule preparations with mean diameters of 1.1 mm and less (1.1, 0.5 and 0.1 mm) were compared. The gastric emptying rate was evaluated by determining the pharmacokinetic parameters of pyridoxic acid, including Vmax (peak excretion rate) and Tmax (time to reach peak excretion rate) after oral administration of micro-capsules containing pyridoxal phosphate as a marker drug to five healthy subjects. When given under fasting conditions, the gastric emptying rates of these preparations, according to Tmax, differed significantly; the preparations with smaller particle sizes were emptied from the stomach at a faster rate than those with larger particle sizes. However, under non-fasting conditions the gastric emptying rates were virtually the same, regardless of particle size, and all the preparations were emptied from the stomach at a much slower rate than when administered under fasting conditions.


Clinical and laboratory work-up prior to hormone replacement therapy in postmenopausal women.

In a retrospective study on 100 female patients (mean age 52 years), with a menopause lasting for 3.5 years, referred to the Menopausal Clinic of Beilinson Medical Center, we studied the pretreatment, clinical and laboratory work-up before administration of hormone replacement therapy (HRT). The work-up consisted of clinical and medical examination and history. Mammography is a necessary test for malignancy exclusion, and also the assessment of lipid metabolism. Pap smear is not so important since cervical cancer is a rare event in Jewish women and pelvic sonography cannot be a decisive diagnostic tool for ruling out malignancy. We conclude that HRT for prevention of osteoporosis and cardiovascular disease should be administered in a menopausal clinic by a gynecologist, after performing a few tests: confirmation of menopause by follicle-stimulation hormone (FSH) and E2, excluding malignancy by mammography, and confirmation of normal lipid metabolism.


Iron balance in pregnancy in relation to anemia.

Blood levels of iron, transferrin and ferritin varied in the course of pregnancy (6th to 42nd week) in 136 women. Analysis of variance showed that the factor "weeks of pregnancy" (< or = 27 or > 27 weeks) was correlated differently with the variables "ferritin" and "iron" according to the presence or absence of anemia (Hb < or = or > or = 11 g/dl). In anemic women the correlation was significant (F-ratio = 5.90; P = 0.018) for iron (which decreased from initial low level until term) but not ferritin, whereas in non-anemic women the correlation was significant (F-ratio = 13.306; P = 0.0006) for ferritin (which decreased to less than 20 micrograms/ml around the 34th week) but not iron. In both anemic and non anemic subjects, transferrin levels increased with weeks of pregnancy. It is concluded that towards the end of pregnancy, some decrease in ferritin (> or = 15 micrograms/ml) is physiological, and in the absence of anemia (Hb > 11 g/dl) iron supplements are not necessary.


Cystic hygromas associated with Turner's syndrome. Report of three cases.

Three cases of cystic hygromas are reported. Two of these were singleton pregnancies diagnosed at 20 weeks' gestation and the other was an affected fetus in a twin pregnancy at 19 weeks gestation. Amniocentesis was done and chromosomal analysis revealed Turner syndrome in all cases. The two singleton pregnancies were terminated by intrauterine installation of PgF2a. The affected fetus of the twin pregnancy died at 24 weeks' gestation and the pregnancy continued.


Quantitative ultrasound diagnosis of endometrial cysts.

We measured the ultrasonic frequency dependent attenuation of ovarian cysts using the spectral difference method to find the difference in the characteristics of attenuation of the endometrial cyst and other ovarian cysts. We investigated an analytical method to measure the ultrasonic frequency dependent attenuation of ovarian cysts and we called this method the boundary echo spectrum method. The endometrial cyst had an attenuation slope of 0.67 +/- 0.27 dB/cm/MHz, and attenuation value was 1.85 +/- 1.27 dB/cm, and it had significantly higher attenuation slope and attenuation value compared with those of serous cystadenoma and mucinous cystadenoma, but no significant difference compared with those of dermoid cyst (fat component). Compared with attenuation slope and attenuation value, attenuation slope is superior because of smaller standard deviation and better linearity between water immersion and transabdominal method.


Maternal fructosamine and glycosylated haemoglobin in the prediction of gestational glucose intolerance.

The value of maternal glycosylated haemoglobin (HBA1c) and fructosamine in the prediction of gestational diabetes is debated. One hundred high risk patients were grouped as normal, impaired glucose tolerance (IGT) and gestational diabetes mellitus, according to the WHO criteria, after 2 hours, 75 g oral glucose tolerance test (OGTT). Maternal HBA1c and fructosamine were measured at different gestational ages and at the start of labour. The aim of the study was to determine the most sensitive predictor of abnormal glucose tolerance. Maternal fructosamine was higher in gestational diabetics than in the other two groups, but the difference was not of statistical significance. The values for normal and IGT groups overlapped markedly. The fructosamine test sensitivity was 12.2%, specificity was 94.7% and predictability was 75%. Glycosylated haemoglobin was significantly higher in IGT and gestational diabetes mellitus (GDM) groups than in the normal group after 36 weeks of gestation. At 32 weeks or less the difference was not of statistical significance. As with fructosamine, there was a wide range of value that overlapped markedly, particularly between the normal and IGT patients. The HBA1c test sensitivity was 19.1%, specificity was 95% and predictability was 81.1%. This suggests that both HBA1c and fructosamine have very low sensitivity as predictors of gestational glucose intolerance.


Bromocriptine (Bromergon, Lek) in the management of premenstrual syndrome.

The efficacy of bromocriptine (Bromergon, Lek) was studied in a group of 21 women with premenstrual syndrome (PMS). To qualify for inclusion, the patients had to have a score of 20 or more on Casper's Analog Self-Rating Scale for Premenstrual Tension Syndrome completed during the last premenstrual week. The study was designed as a double-blind, randomized, cross-over trial introduced by a wash-out cycle. Patients received Bromergon in a daily dose of 5 mg from cycle day 10 to the onset of menstruation for two consecutive menstrual cycles, followed by two placebo cycles or vice versa. The subjects were instructed to complete the scale every three days from cycle day 3 to the onset of menstruation. A statistically significant improvement due to the administration of Bromergon was observed in symptoms associated with overreactiveness to normal prolactin levels, i.e. abdominal tension, edema, weight gain and breast tenderness. Scores on the linear analog scale and physician's assessments differed regarding psychological symptoms. The investigators observed no difference in the presence of psychic symptoms in the treatment-free period, on Bromergon therapy and during the administration of placebo. On the other hand, self-rating scores reflected an improvement in the presence of depression and irritability during Bromergon treatment. The results obtained suggest that Bromergon may be a useful agent for the treatment of somatic symptoms associated with PMS, while it seems somewhat less effective in PMS cases where psychic symptoms are the major complaint.


Decrease of cellular growth potential in "in vitro" culture of amnions with premature rupture of membranes.

The "in vitro" cellular growth of 8 amniotic membranes from preterm deliveries with premature rupture of membrane (PROM) in absence of risk factors as cervical or vaginal infection (microbiologic negativity), cervical incontinence and other mechanical factors, was compared with cellular growth of 9 amnions from preterm deliveries without PROM. Amniotic membranes were set up in the Eagle basal medium with Earle salts and heat-inactivated fetal bovine serum (10%), gentamicin 50 micrograms/ml and amphotericin B 0.5 micrograms/ml. The results suggested that the growth potential of the cells (epithelial cells and fibroblasts) obtained from amnions with PROM was lower than that of cells obtained from amnions without PROM. We postulated that the premature rupture of membranes in patients without risk factors for PROM, would be conditioned by an intrinsic decrease of cellular growth potential.


Neonatal complications and risk of intraventricular-periventricular hemorrhage.

We have prospectively studied 117 premature infants < or = 1500 gm (VLBW) to assess the relationship between maternal, obstetric, fetal and newborn complications and the grade of periventricular-intraventricular hemorrhage (PVH-IVH). PVH-IVH was documented by cranial ultrasonography in 41% of surviving neonates. 83% of infants with PVH-IVH grade I-II survived as compared to the 39% of infants with PVH-IVH grade III-IV (p < .001). Maternal and obstetric complications were not associated with PVH-IVH (NS). Newborn respiratory complications (p < .004) and major infections (p < .02) are independent variables associated with PVH-IVH. Immaturity at delivery, metabolic acidosis, respiratory distress syndrome and recurrent apnea are important mechanisms of cerebral injury contributing to severity of PVH-IVH.


Lack of in vivo transcription of Acetabularia mediterranea 1175 bp ctDNA fragment homologous to the Drosophila per locus.

The period (per) locus of Drosophila melanogaster has a fundamental role in the expression of biological rhythms. A DNA sequence homologous to a short region of the Drosophila per locus was detected in the chloroplast of Acetabularia mediterranea. A 1175 bp DNA fragment containing the sequence was used as a probe in 'Northern' hybridization experiments. It was found that this DNA was not transcribed or only marginally transcribed in A. mediterranea, at least at the developmental stage just prior to cap formation. It seems that the 1175 bp ctDNA fragment is not involved in the Acetabularia biological rhythm mechanism.


Effects of calcitonin and calcitonin gene-related peptide on 3H-thymidine incorporation into DNA of rat thyroid lobes in vitro.

The effects of a 4 h incubation of rat thyroid lobes, in the presence of calcitonin (CT) and calcitonin gene-related peptide (CGRP) on the incorporation of 3H-thymidine into DNA, were investigated. In other groups the thyroid lobes were incubated during exposure to CT and thyrotropin (TSH), and to CGRP together with TSH. All concentrations of CT (10(-6)-10(-8) M) revealed a tendency towards lowering 3H-thymidine uptake, but the effect was not statistically significant. The influence of CGRP was dose-dependent; the lowest concentration of CGRP (10(-9) M) significantly enhanced DNA synthesis in the incubated rat thyroids; an intermediate dose of the peptide (10(-8) M) had no effect, while the highest concentration of CGRP (10(-7) M) decreased 3H-thymidine incorporation. Calcitonin (10(-7) M), as well as CGRP (10(-8) M), suppressed the stimulatory effect of TSH on 3H-thymidine incorporation.


Clinico-immunogenetic study on Egyptian multicase tuberculous families.

Thirteen multicase Egyptian families (having more than one sib affected) with pulmonary tuberculosis have been studied. They include 26 parents (4 were tuberculous) and 53 sibs (30 tuberculous and 23 healthy). For all of them the following have been carried out: (a) Clinical, radiological, and bacteriological examination for diagnosis and evaluation of the disease severity; HLA-antigen determination using 9(A), 16(B) and 6(DR) antigens. The analysis of data revealed: (1) high incidence of tuberculosis among sibs in families having A2 B5 in their haplotypes compared to those having A2 X or B5 X--affected sibs with A2 B5 showed more severe manifestations than those having only one of the two antigens; (2) aggregation of HLA concordance among the sib pairs, both fully identical and haploidentical, while none of the sib pairs is non-identical; (3) Lod score studies showed linkage between the genetic control of susceptibility to pulmonary tuberculosis and HLA; (4) identity by descent study confirms the dominant pattern of transmission. The recommendation is that in a clinical setting of genetic counselling healthy individuals having either A2 or B5 antigens in their haplotypes should be vaccinated with BCG. Furthermore tuberculous patients having these HLA antigens should be managed aggressively, especially those having A2 B5 haplotypes in whom the disease is likely to run a severe course.


Lack of association of the alpha-1-antitrypsin PIZ allele with rheumatoid arthritis or with its extra articular complications.

PIZ allele frequencies were defined by PCR amplification and hybridization using a PIZ SSO (sequence specific oligonucleotide) probe. The groups studied included 64 normal controls, 104 subjects with rheumatoid arthritis (RA) without any extra-articular features, 29 of whom had severe arthritis and 31 of whom had mild RA. The extra-articular subsets include 41 with RA-bronchiectasis (RA-BR), 21 with bronchiectasis without RA (BR), and 23 with RA and pulmonary fibrosis (RA-PF). Fifteen RA subjects with obstructive airways disease (RA-OAD) were compared to 25 RA patients with normal lung function tests. Using Fishers' exact test and chi-squared statistical analysis with Yates correction, no statistically significant associations were found between PIZ and any of the groups studied. Thus in this population there is no evidence that PIZ either increases susceptibility to rheumatoid arthritis or affects the risk of pulmonary complications or the severity of arthritis in subjects with rheumatoid arthritis.


Effect of fasting, branched-chain amino acids, and glucocorticoids on histone H1 extractability from rat skeletal muscle.

The effect of 72 h fasting, nutritional therapy of fasted rats, and acute and chronic glucocorticoid treatment on the yield of histone H1 from rat hind limb muscles was determined. Fasting significantly enhanced the extractability of muscle H1. The effect of treating starved rats with glucose alone, or with glucose supplemented with branched-chain amino acids (BCAA), or with two commercial preparations of mixtures of essential and non-essential amino acids was evaluated. Treatment of starved rats with glucose alone significantly decreased H1 extractability from muscles, but isocaloric treatment with glucose supplemented with BCAA or two commercial preparations of amino acid mixtures was more effective. Glucocorticoid treatment for 5 days enhanced the yield of H1 from muscles less than starvation. The enhanced H1 extractability from muscles noted in starved rats is similar to that reported in rats with insulinopenic diabetes and may reflect changes in nuclear fragility.


Relationship between inhibitor of extrathyroidal 5'-deiodinase activity and serum free fatty acid in children with nonthyroidal illness and acute ketosis.

To clarify whether serum free fatty acid (FFA) is an inhibitor of extrathyroidal conversion (IEC) of thyroxine (T4) to thyronine (T3), we measured the concentration of FFA, IEC activity and thyroid hormones in normal subjects, acute ketotic children and children with low T3 syndrome due to nonthyroidal illness (NTI). Iodothyronine (I) 5'-deiodinase activity was assayed with reverse triiodothyronine (rT3) as substrate and liberated 125I-was measured. The IEC was determined by the inhibition of I 5'-deiodination by ether extract of sera or standard oleate solution. IEC values were represented as mM oleate. The serum concentration of FFA was 0.470 +/- 0.117 (SD) mM in 11 normal subjects, and it was significantly higher (1.242 +/- 0.248 mM; P < 0.01) in 10 acute ketotic children and in 7 samples from 6 NTI children (0.904 +/- 0.530 mM; P < 0.05). In contrast, there was no difference in IEC among three groups (normal subject, 0.451 +/- 0.069 mM; acute ketosis, 0.437 +/- 0.040 mM; NTI, 0.465 +/- 0.224 mM). No correlations were found between IEC activity and the serum FFA concentration or thyroid hormones in 28 samples from three groups. The sequential changes in serum thyroid hormones, FFA and IEC in 3 of 6 NTI children revealed no consistent relationship. Furthermore, one NTI child had significantly high IEC (> 1.000 mM) but its serum FFA (1.182 mM) was below the mean value for the acute ketotic group. These results indicate that 1) many NTI patients may bear no relation to IEC and 2) IEC may not be caused by serum FFA only but includes several factors.


Generalized resistance to thyroid hormone (GRTH) in a family: case studies.

A familial case of generalized resistance to thyroid hormone (GRTH) is described. A 17-year-old man (case 1), who had been treated with methimazole under the diagnosis of Graves' disease and his 11-year old sister (case 2) visited our clinic for the evaluation of their thyroid function. They lacked the signs and symptoms of thyrotoxicosis in spite of extremely high serum thyroid hormone levels. Their plasma TSH levels were not suppressed, but in fact markedly increased after TRH loading. Their peripheral indices of thyroid hormone were within normal limits and were not influenced by exogenous T3 administration. Even 150 micrograms T3 administration for 7 days did not fully suppress the TRH-stimulated TSH level in case 2. The two patients thus were diagnosed to have GRTH. Sera from their father and another sister showed identical abnormalities.


The effect of DHAS on steroidogenesis of the human corpus luteum.

To examine whether or not dehydroepiandrosterone sulfate (DHAS) is a substrate for steroidogenesis in the corpus luteum, we studied 17 women in the luteal phase, the follicular phase, and after castration. Following suppression of adrenal function with dexamethasone, DHAS was administered intravenously and the serum levels of DHAS, dehydroepiandrosterone (DHA), androstenedione (ADS), testosterone (T), 17 beta-estradiol (E2) and progesterone (P) were measured serially for 24 h. An obvious increase in the serum levels of all steroids except for E2 and P was observed in each subject for at least 8 h after DHAS administration. To evaluate the effect of DHAS on the serum levels of the steroid hormones, the integrated response area (IRA) was calculated for each hormone in all the subjects. The IRA values for ADS, T and E2 (at 2 and 4 h) in the luteal phase group were significantly higher than in the other DHAS treated groups, and the IRA values for DHA and P tended to be higher than in the other groups. These results suggest that the corpus luteum utilizes serum DHAS as a substrate for steroidogenesis.


Characterization of parathyroid hormone-related protein in the human term placenta.

To characterize parathyroid hormone-related protein (PTHrP) in the human placenta, we measured PTHrP-like immunoreactivity (PRP-LI) in the term placenta and studied the elution profiles of placental tissue extracts on Sephadex G-75 chromatography with a specific RIA. We also examined the gene expression of PTHrP mRNA by Northern blot analysis and the localization of PRP-LI in the placenta by immunohistochemistry. The amount of PRP-LI in placental extracts (n = 7) was 20.9 +/- 2.2 pg/g wet tissue (mean +/- SE). Dilution curves of placental tissue ran parallel to those of synthetic PTHrP (1-34) standards. Sephadex G-75 gel chromatography demonstrated two major PRP-LI peaks; the first peak was eluted around the molecular size between 10 kilodaltons (Kda) and 20 Kda and the other around 5 Kda. Northern blot analysis of PTHrP mRNA extracted from placental tissues showed a major hybridization signal around 18S. PTHrP immunohistochemistry showed PRP-LI staining in the cytoplasm of syncytiotrophoblasts and stroma cells (Hofbauer cells) in the term placenta. These results suggest that syncytiotrophoblasts and stroma cells in the term placenta synthesize PTHrP in two major molecular forms, 10 Kda-20 Kda and around 5 Kda.


Clinical significance of adrenal computed tomography in Addison's disease.

Adrenal computed tomographic (CT) scanning was conducted in twelve patients with Addison's disease during the clinical course. In tuberculous Addison's disease (n = 8), three of four patients examined during the first two years after disease onset had bilaterally enlarged adrenals, while one of four had a unilaterally enlarged one. At least one adrenal gland was enlarged after onset in all six patients examined during the first four years. Thereafter, the adrenal glands may atrophy bilaterally, in contrast to adrenal glands in idiopathic Addison's disease, which atrophy bilaterally from disease onset (n = 2). Adrenal calcification was a less sensitive clue in tracing pathogenesis, i.e., adrenal calcification was observed in five of eight patients with tuberculous Addison's disease, but not in idiopathic patients. Thus, adrenal CT scanning could show the etiology of Addison's disease (infection or autoimmunity) and the phase of Addison's disease secondary to tuberculosis, which may be clinically important for initiating antituberculous treatment.


Transient extreme insulin resistance in shock during diabetic ketoacidosis.

Transient extreme insulin resistance was encountered during an episode of diabetic ketoacidosis (DKA) in an insulin-treated diabetic patient. On admission, the plasma glucose level was 1241 mg dl-1 and arterial blood pH 6.895 with HCO3- 4.7 mEql-1. An intravenous bolus injection of 20 units, followed by continuous infusion of 20 units h-1 of short-acting regular human insulin, was instituted. Ischemic myocardial changes were noted on the initial electrocardiogram, therefore fluid replacement was limited to 1,000 ml of 0.9% saline solution in the first hour. As the plasma glucose level declined by only 203 mg dl-1 (41 mg dl-1 h-1) in the first 5 h, the insulin dose was doubled every 2 h. At hour 4, the patient developed circulatory shock which required vasopressor support and respiratory assistance. A plasma glucose level of 300 mg dl-1 was not achieved until the total dosage of insulin amounted to 91,580 units at hour 25. Insulin resistance was not observed from that point on. The patient had neither insulin antibodies nor anti-insulin receptor antibodies in serologic testing. The insulin binding characteristics of the patient's erythrocytes were similar to those from healthy controls both with and without experimental acidosis and with a high level of beta-hydroxybutyrate. Among multiple potential factors, the severe shock associated with DKA has been considered as a primary cause of the transient severe insulin resistance in this case.


Thyroxine-binding globulin variant (TBG-Kumamoto): identification of a point mutation and genotype analysis of its family.

Thyroxine-binding globulin (TBG) is the major thyroid hormone transport protein. Several inherited TBG variants resulting in partial or complete TBG deficiencies have been shown to be caused by either one or two nucleotide substitutions, or one nucleotide deletion in the coding regions of the TBG gene. In this report, a Japanese female patient (proband) with hyperthyroid state, whose lower TBG levels did not return to normal under the euthyroid state after treatment was examined. Genomic DNA samples from the proband with thyroxine-binding globulin deficiency (termed TBG-Kumamoto) and her family were subjected to the polymerase chain reaction, and the generated DNA fragments were sequenced. A single nucleotide substitution in the codon for the amino acid 363 of native TBG molecule (CCT to CTT) was found, resulting in the replacement of proline by leucine. It was revealed that the proband was a heterozygote and her father was a hemizygote. The mutation was confirmed by the allele-specific amplification of genomic DNAs from the proband and her father using oligonucleotide primers of normal or mutant residues at the 3' position in the polymerase chain reaction. These results indicate that the abnormality of TBG-Kumamoto is the consequence of this mutation. Genetically, this point mutation observed in TBG-Kumamoto might be classified as a new type of TBG deficiency.


Source of prolactin in human follicular fluid.

To analyze whether prolactin (PRL) in human follicular fluid (FF) is synthesized locally or derived from the circulation, PRL concentrations of plasma and FF were determined in the patients after ovarian stimulations. The amounts of PRL messenger ribonucleic acid (mRNA) in the follicular tissues during different menstrual phases were also determined. The FF PRL concentration was correlated positively with plasma PRL and highest estradiol levels during the stimulatory cycle. No PRL mRNA sequence was detected in the RNAs extracted from follicles at any stage in the menstrual cycle, although beta-actin mRNA was detected in all samples. In a comparison with pituitary RNA, the PRL mRNA concentration in ovarian follicular tissues seemed to be 10,000 times less than that in the pituitary. These results suggest that FF PRL may not be synthesized locally, but derived from the pituitary via the circulation through passive diffusion, and thus regulated by estrogen.


Immunohistochemical evidence that rat FSH cells contain beta II-subspecies of protein kinase C.

Immunocytochemical double-staining analysis revealed that in the rat anterior pituitary 86% of cells containing the beta II-subspecies of protein kinase C also contained follicle stimulating hormone (FSH), and that 22% of these FSH cells expressed the beta II-subspecies. These findings suggest a close relationship between the beta II-subspecies of protein kinase C and FSH regulation.


The relationship between education and risk factors for coronary heart disease. Epidemiological analysis from the nine communities study. The Research Group ATS-OB43 of CNR.

In nine samples of adult populations (2707 males and 2871 females, aged 20-59 years) we studied the relationship between educational level and several lifestyle factors at risk for coronary heart disease (CHD), (i.e., smoking, alcohol consumption, dietary fat intake, sedentary behaviour at work and leisure) and the association between education and certain CHD risk factors (i.e., total cholesterol, HDL-cholesterol, triglycerides, systolic and diastolic blood pressure, body mass index). The data were analyzed separately in samples from North, Central and Southern Italy. The results show that educational level is often associated to the lifestyle factors considered here. This association was positive for both men and women for physical activity at leisure and work stress and only for women with respect to smoking. It was negative for both men and women for alcohol consumption and physical activity at work and for men only for cigarette smoking. The age-adjusted mean levels of the CHD risk factors show some significant differences among subjects with different educational levels, which were not always the same for the three geographical areas. This was with the exception of BMI in females, which appears negatively associated to education in all areas. These differences decreased after adjustments were made for daily cigarette smoking, wine consumption and dietary fat intake. Education seems to play a determining role in lifestyle, however, its direct and indirect effects on some major CHD risk factors are somewhat different in areas at different socio-economic conditions.


Correlation between mortality trends of ischaemic cardiopathy and some nutritional factors in Spain 1968-1986.

After describing the evolution of mortality from ischaemic cardiopathy (IC) in Spain from 1951 to 1986, which is tending to stabilize in some age groups, and from cerebrovascular accidents (CVA), which is clearly declining, an attempt is made to relate these developments to the prevalence of the main risk factors (hypertension, cholesterol, tobacco) associated with IC and CVA. Certain advances, though of a limited number, have been made in recent years in the control of arterial hypertension in Spain, although campaigns on a national scale as in other countries have not been carried out. Regarding alimentary factors, there is an obvious increase in the consumption of food rich in proteins and animal fats, abandoning to a great extent the traditional "Mediterranean diet", with health care action being limited to the improvement of nutrition education of the public. Furthermore, the consumption of tobacco has been increasing in Spain during the study period in spite of health legislation in force in recent years. It is therefore deduced that there is no obvious relationship between mortality due to IC and CVA and the prevalence of the main risk factors associated with these diseases, especially when taking into account that preventive actions on a public health level have been very limited.


The independent effect of habitual cigarette and coffee consumption on blood pressure.

The authors investigated the possible relation between habitual cigarette and coffee consumption and blood pressure (BP) levels in 7506 men and 2095 women. The study population were managers and employees examined in northern Italy between 1986-1988. In particular, the hypothesis of a substantial independence between smoking-BP and coffee-BP was tested. BP levels were corrected for age, body mass index, physical activity, and alcohol consumption by analysis of covariance. Significantly, smoking was inversely related to BP, both in men (SBP, P < 0.001, DBP, P < 0.001) and women (SBP, P = 0.001, DBP, P = 0.012). In particular, the BP of non-smoking men, SBP/DBP, was 131.0/83.5, whereas in male smokers up to and over 20 cigarette/day, BP was 128.1/82.0 and 128.1/82.1 respectively. Coffee consumption was related to BP levels in men (SBP, P < 0.001; DBP, P = 0.009), but not in women (SBP, P = 0.320; DBP, P = 0.982). BP in male subjects was 131.3/83.5 in non-drinkers, 130.7/83.3 in those drinking 1-3 cups/day, 128.4/82.6 and 127.2/81.8 in drinkers of 4-5 and over 5 cups/day, respectively. No significant interactions were demonstrated, thus the relationship between habitual smoking and coffee consumption with BP appears to agree with an additive model.


Cardiovascular risk factors and prevalence of coronary heart disease in type 2 (non-insulin-dependent) diabetes.

The relationship between cardiovascular risk factors and the prevalence of coronary heart disease was examined in 152 Type 2 diabetic patients (65 men, 87 women) aged 35-54 years and in 105 randomly selected control subjects (46 men, 59 women). Coronary heart disease, defined by symptoms and ECG abnormalities, was 1.2 times higher in male and 3.4 times higher in female diabetic patients than in the controls. In logistic regression analysis (including diabetes, age, body mass index, triglycerides, HDL-cholesterol, non-HDL-cholesterol and hypertension) diabetes showed an independent, significant association to coronary heart disease in women, whereas hypertension was independently related to coronary heart disease in men.


A case-control study of major congenital heart defects in Sweden--1981-1986.

This paper reports the results of a case-control study of major congenital heart defects (CHD) in Sweden. During the period 1981-1986, 1,324 such cases were identified and 2,648 controls were selected. Some common maternal characteristics and exposures were studied using information from prospectively collected data. Possible associations with CHD were found for previous perinatal death, maternal diabetes, epilepsy, hydramnios and disproportion between fetus and pelvis. More specific associations were observed between previous spontaneous abortion, epilepsy, hydramnios and truncus anomalies and between diabetes and septal anomalies. However, no associations were found with involuntary childlessness, contraceptive use, or smoking.


An epidemiologic study of environmental and genetic factors in congenital hydrocephalus.

Risk factors were studied in 96 children with congenital hydrocephalus (CH) coming from 118,265 consecutive births of known outcome. Hydrocephalus with neural tube defects, intracranial tumors or secondary to brain atrophy were excluded. The prevalence of CH was 0.81 per thousand. Diagnosis was performed prenatally in 41 cases. Forty-three (44.8%) of the cases had hydrocephalus without other malformations (isolated hydrocephalus), 18 (18.7%) infants had recognized chromosomal or non-chromosomal syndromes and 35 children (36.4%) had multiple malformations. Each case was matched to a control. Weight and length at birth of children with hydrocephalus were less than in the controls (p < 0.001). The weight of the placenta was lower than in the controls (p < 0.05). The pregnancy with a hydrocephalic child was more often complicated by threatened abortion, polyhydramnios and oligohydramnios. The mothers of children with hydrocephalus and multiple malformations had used oral contraceptives during the first trimester of pregnancy more often than the mothers of the controls. No differences appeared between the mothers of children with CH and the controls for the other risk factors studied: parental age, parity, previous pregnancies, previous stillbirths, smoking, diabetes, epilepsy, X-rays, hypertension, fever "flu", medication and occupational exposure. There was an increase of parental consanguinity in the parents of our patients (6.2% v. 1.1%, p < 0.001) and first degree relatives had more non-cerebral malformations than the controls (7.3% v. 3.2%, p < 0.05).


Are homes for the elderly still a risk area for HBV infection?

To verify whether improvements in hygiene affect the risk of HBV infection, a seroepidemiological survey on HBV infection was carried out in a home for the elderly with continuous-care accommodation. HBV serum markers were tested in 315 subjects and the results of HBV infection were compared to those observed in two different types of nursing homes for the elderly from an earlier seroepidemiological study carried out in 1978. In addition, results from a cohort of a pre-geriatric population living in their own homes in the same geographical area surveyed in 1980 were compared to the present study. A statistically significant lower prevalence of HBV serum markers in the new home for the elderly compared to the two types studied in 1978 was observed. No difference was found between the new institutionalized study group and the cohort of a pre-geriatric population surveyed in 1980. These results reflect the improved sanitation in homes for the elderly and show that the elderly have very few opportunities to become infected, even in a close cohabitation system.


Knowledge, attitudes and practices of Greek health professionals, in relation to AIDS.

In order to improve educational programmes directed at health care workers we investigated their knowledge, attitudes and practices in relation to HIV/AIDS. An anonymous self-administered questionnaires was distributed to 609 health care workers. Of these, 59.6% agreed to participate (42.4% of the medical doctors, 74.3% of the nurses and 79.6% of the laboratory technicians, health visitors and other health care workers). All studied groups believed that their knowledge of HIV modes of transmission (84.3%) was sufficient. In contrast, a relatively small percentage reported knowledge of the clinical spectrum of HIV infection (48.8%) and the diagnostic assays (57.6%). Nearly all the study participants believe (92.8%) that there is a risk of acquiring HIV infection during the hospitalization of HIV/AIDS patients. Obligatory screening of all patients was reported by nearly all participants (90.6%) as a chance to minimize their occupational risk. Although health care workers reported satisfactory knowledge of safety measures (87.0%), only 56.7% used gloves and 38.8% accept the hospitalization of HIV/AIDS patients. In spite of the educational programmes for AIDS in Greece, this study demonstrates that health professionals' knowledge and precautionary measures are not sufficient. As a result, a small percentage of them treat AIDS patients without discrimination. There is an urgent need to implement specific educational programmes for health professionals so that they will safely provide high quality care to people affected by HIV/AIDS.


Head injuries after serious bicycle accidents.

Between 1987 and 1988 there were 47 serious or fatal injuries among bicycle riders in the city of Tel Aviv-Yafo (Serious injury was defined as being hospitalized for at least 24 hours). Collisions with vehicles, mostly cars, were responsible for about 80% of these cases. Two-thirds of the accidents occurred in adults aged 20 and over. We were able to trace the records of 24 of the 47 who were injured. Head trauma was the most common form of severe injury, occurring in 11 of the 24 cases. Two of the 11 died instantly and one died after 14 days of hospitalization, all from severe brain damage. Eight suffered severe head trauma, 7 of which had brain injury and 2 of the 7 were left with severe residual brain damage. In view of the efficacy of bicycle helmets in preventing head trauma there is a great need to expand their use among bicyclists in Israel.


The epidemiology of head injury in Cantabria.

The epidemiology of head injury was studied in Cantabria, Spain, using a methodological design consisting of a cross-selectional analysis of one year of duration and an additional one year follow-up of all the patients included in the initial sample. The 477 cases identified represent a rate of 91/100,000, with males showing a head injury rate 2.7 times higher that than for females. Sixty per cent of all cases involved traffic accidents, falls accounted for 24% and industrial accidents were the cause in 8%. The annual age-adjusted mortality rate was 19.7/100,000. Over 92% of all deaths occurred prior to hospital admission. The presence of alcohol intoxication was evaluated in 211 cases by determining the osmolar gap. It was found that 51% of all the cases examined presented clear evidence of acute alcohol intoxication.


Non-melanoma skin cancer: an evaluation of risk in terms of ultraviolet exposure.

A retrospective study of 143 patients histologically diagnosed with non-melanoma skin cancer (NMSC) was carried out in order to evaluate the influence of ultraviolet (UV) radiation on the appearance of more than one NMSC in the same person. Descriptive statistical and logistic regression analyses were carried out for each variable and its possible interaction, in order to determine the potential appearance of multiple NMSC. The results obtained were in agreement with those of earlier studies. A significant relationship was observed between occupational UV exposure and individuals with more than one NMSC. Those patients tended to be blue-eyed and were chronically exposed to UV radiation as a result of occupational activities (although not always in leisure activities); most did not take protective measures such as the use of hats or creams.


Occupational physical activity and colon cancer risk in Turkey.

A case-control study of 107 colon cancer cases and 486 controls from an oncological clinic in Istanbul was conducted to examine the association between occupational physical activity and colon cancer in Turkey, where incidence of this disease is low. Only two of the four activity measures showed evidence of an increased colon cancer risk for sedentary jobs (time spent sitting OR = 1.5 and occupational energy expenditure OR = 1.6); neither was statistically significant. Subjects below age 55 showed higher risk associated with sedentary jobs than did the older age group, probably due to their adoption of a more western lifestyle, including dietary habits, less activity, and other factors that may interact to increase the risk of colon cancer.


Epizootics of Salmonella infection in poultry may be the result of modern selective breeding practices.

This paper discusses the hypothesis that a major factor in the epizootics of Salmonella infection in poultry is a declining host genetic diversity. A computer model is described which is based on models that have been previously used to investigate host-pathogen coevolution in cereal crops. It is shown that, as host genetic diversity declines, parasite diversity also declines to a lower equilibrium level. With a highly diverse host, parasite numbers decline to zero. With a homogeneous host population, after an initial decline, there is a rapid increase in parasite numbers, due to the selection of a particularly well adapted parasite strain. This simple computer simulation is used as the basis for a discussion of the literature supporting the suggestion that a major factor in the epizootic of Salmonella in poultry is related to the low genetic diversity of commercial poultry flocks.


Features of cholera and Vibrio parahaemolyticus diarrhoea endemicity in Calabar, Nigeria.

The clinical and epidemiological features of acute vibrio diarrhoeal disease were studied in 881 patients seen at the University of Calabar Teaching Hospital (UCTH), Calabar, Nigeria, between January and December 1989. Stools and rectal swabs of patients and randomly-selected control subjects were microscopically and culturally examined for the presence of enteric pathogens. Households of vibrio diarrhoea cases and matched controls were visited for ecologic studies. Of a total of 108 (12.3%) culturally-confirmed bacterial diarrhoeas, 47 (43.5%) were due to Escherichia coli, 33 (30.6%) to Vibrio cholerae-01 (classical and El Tor biotypes) and V. parahaemolyticus, while shigellae and salmonellae accounted for 29 (26.9%) and 9 (8.3%) cases, respectively. Most cholera case households clustered within the ancient neighbourhood of the inner city, characterized by poorly developed water and sewage disposal systems. A preponderance of vibrio diarrhoea patients were children < or = 10 years. Adult cases involved mostly females. The only case of diarrhoea-related death involved an eight-month old child with kwashiorkor and V. parahaemolyticus infection. Incidence of vibrio diarrhoeas was seasonal, with most cases occurring during the dry season followed by subsidence at the onset of rainy season. Bimodal peaks of vibrio diarrhoeal episodes observed over the period appeared to coincide with periods of acute water scarcity, high temperature, increased fishing activities and trade traffic on the Calabar River estuary. Of the environments sampled, only clam shells from a case household and river sediments yielded vibrio pathogens on culture. Ecological factors that are capable of stabilizing a focus of vibrio diarrhoea endemicity in this area are highlighted.


A survey of urease-positive Vibrio parahaemolyticus strains isolated from traveller's diarrhea, sea water and imported frozen sea foods.

The frequency of urease-positive Vibrio parahaemolyticus among isolates from patients, imported frozen sea foods and the environment (sea water) was studied. The highest isolation frequency of urease-positive V. parahaemolyticus was found in clinical isolates (11.2% out of 204 strains examined). Urease-positive V. parahaemolyticus was found in 5.7% of 88 frozen sea food-isolates examined, but no strains isolated from sea water were urease-positive. The isolates were further examined for the production of thermostable direct hemolysin (Vp-TDH) and its related hemolysin (Vp-TRH). Both are possible pathogenic toxins produced by mostly clinical isolates of V. parahaemolyticus. Urease-positive strains have a tendency to associate with clinical isolates producing both or neither Vp-TDH and Vp-TRH. Rabbit ligated ileal loops test was performed with several strains of urease-positive and -negative clinical isolates, and we found that some strains producing urease, even those which do not produce Vp-TDH or Vp-TRH, caused intestinal fluid accumulation.


Diversity of resistance phenotypes and plasmid analysis in multi-resistant 0:12 Pseudomonas aeruginosa.

Antibiotic resistance phenotypes, plasmid content and ability of conjugal transfer of antibiotic resistance genes of 35 multi-resistant Pseudomonas aeruginosa strains were examined. The strains were isolated in 12 Greek hospitals and the majority of them (80%) belonged to serotype 0:12. The isolates were distributed to a variety of different antibiotic resistance phenotypes. Plasmid analysis showed that 10 isolates harboured plasmids ranging in size from 20 to 100 Mda. Among these strains, four carried plasmids of 100 Mda, two strains had 60 Mda plasmid each while in three strains the plasmids detected were 65, 25 and 20 Mda, respectively. One strain harboured two plasmids of 100 and 60 Mda. All strains containing plasmids belonged to 0:12 serotype, except the one harbouring the 25 Mda plasmid, which belonged to serotype 0:6. Using a P. aeruginosa recipient resistant to rifampicin and ciprofloxacin, conjugal transfer was achieved in two occasions. These plasmids, 100 Mda in size, encoded high-level resistance to both gentamicin and tobramycin whereas resistance to other drugs was not transferable. Interestingly, all 100 Mda plasmids, including the self-transferable ones, were found to share a certain degree of homology as judged by restriction analysis. It is suggested that both resistance phenotypes and analysis of plasmid content might be useful in subdividing 0:12 multi-resistant P. aeruginosa.


Case-control study of congenital malformations.

To determine potentially teratogenic influences in Belgrade, a group of 113 mothers who gave birth to severely malformed infants and a control group of 195 mothers with normal infants were interviewed using a structured questionnaire. Statistically significant differences between the two groups were found in the mother's family history of congenital malformations (P < 0.05) and the mother's diseases during the pregnancy (P < 0.01). Infections in the first trimester were particularly more prevalent in case mothers (OR = 7.70; P < 0.01). Mothers did not differ significantly according to exposure to organic solvents, supportive therapy during the pregnancy, use of oral contraceptives, or other personal habits.


Influence of different upper age limits on the "Years of Potential Life Lost" index.

The use of 65, 70 or 75 years as upper age limits for the "Years of Potential Life Lost" index (YPLL) could influence the relative importance assigned to different causes of premature death. Data from a representative year (1987) in Catalonia (Spain), show that health priorities and comparability among studies are not affected by the use of these upper age limits.


Low risk of mother to infant transmission of hepatitis B virus in Guipúzcoa (Basque country, northern Spain).

The prevalence of HBsAg carriers in 18,196 pregnant women (64% of women who gave birth in Guipúzcoa in 1986-1991) was 0.61% (0.43% for the last two years of the study). Three of the carriers were also HBeAg/HBV-DNA positive and two were anti-HDV positive. Anti-HBc prevalence was 6.5% in 602 20-40 year old women and 1.6% in 428 girls 10-11 years old (0.47% of gypsy ethnic subjects are not included).


IgA antichlamydia antibodies as a diagnostic tool for monitoring of active chlamydial infection.

Chlamydia trachomatis isolation in culture is the best means of chlamydial infection diagnosis. Antichlamydial antibodies, if present, may also serve as diagnostic markers. In eleven patients with positive C. trachomatis culture and serological positive response, specific IgA and IgG antibody titers were measured before and after treatment. In all cases, cultures became negative after treatment and IgA titers decreased rapidly, while IgG levels remained high. Thus, presence of specific IgA antibodies in a single sample may serve as a diagnostic tool for monitoring of active chlamydial infection.


Human chorionic gonadotrophin (hCG) in the management of recurrent abortion; results of a multi-centre placebo-controlled study.

An international ten-centre double-blind trial comparing hCG with placebo in the management of habitual abortion was conducted. The dose regime for hCG used was 10,000 IU i.m. on first diagnosis of pregnancy, 5000 IU thence twice weekly to week 12, followed by once weekly up to week 16. Identical ampoulage of placebo was used. Seventy-five patients completed the trial. Thirty-six received hCG and thirty-nine placebo. 83% of the pregnancies on hCG were successful compared with 79% on placebo (P = 0.45). Of the 25 defined as having no cause for their habitual abortion history, 83% on hCG were successful, as were 85% on placebo (P = 0.73). No significant differences were found between the two therapies in terms of delivery weight, placental weight or neonatal Apgar score. This study fails to confirm previous promising placebo-controlled data advocating the use of hCG in habitual abortion.


Convention for reporting amniotic fluid pressure.

A proposed convention sets zero pressure at atmospheric pressure at the level of the surface supporting the supine patient and takes the cm of water as the unit of measurement. This ensures that measurements made in different clinics will be comparable. Statements about 'higher' and 'lower' pressures, in different patients or in the same patient in different situations, should specify the level of the uterus to which the statement applies.


Fetal malformations associated with chronic polyhydramnios in singleton pregnancies.

Forty-one congenital malformations were found in 28 newborns in a group of 197 cases of chronic polyhydramnios in singleton pregnancies. Of these, a total of 61% (17/28) was antenatally diagnosed ultrasonically. Nine newborns (4.5%) had malformations of the central nervous system (CNS), 9 (4.5%) cardiovascular malformations, 8 (4.1%) musculoskeletal anomalies, 7 (3.6%) malformations of the urinary and reproductive system, 4 (2%) respiratory system anomalies and 3 (1.6%) anomalies of the gastrointestinal system. Chromosomal abnormalities were found in three cases. As the association of polyhydramnios with fetal congenital anomalies is quite high (14.2% in our series), it is imperative to make a major effort to antenatally detect as many cases as possible. This means that in the case of hydramnios the following are required: ultrasound examination by an expert, echo ultrasonography when no other abnormalities are detected, and maybe even a chromosomal analysis.


The influence of presentation and method of delivery on neonatal mortality and infant neurodevelopmental outcome in nondiscordant low-birthweight ( < 2500 g) twin gestations.

The effects of birth order, presentation and method of delivery on neonatal mortality and neurodevelopmental outcome in nondiscordant low birthweight ( < 2500 g) twin gestations were evaluated. Sixty-four sets of twins were included in the study; 29 sets were in vertex/vertex presentation (Group I), 25 sets in vertex/breech (Group II) and in 10 pregnancies the first twin was nonvertex (Group III). The rate of favorable neonatal outcome (survival and normal neurodevelopmental outcome after a 2-year follow-up) was lower in pregnancies in which at least one twin was in nonvertex presentation (50/70 vs. 52/58 P = 0.02). However, after adjustment by multiple logistic regression analysis for the effects of gestational age, birthweight, birth order and educational level of the mother, this difference was not statistically significant (odds ratio = 0.6; 95% confidence interval 0.44 to 5.9; P = 0.5). In pregnancies in which at least one of the twins was in nonvertex presentation, delivery by cesarean section did not affect the rate of favorable neonatal outcome (odds ratio = 1.8; 95% confidence interval 0.48 to 12.9; P = 0.8). The results of this study suggest that in low birthweight twin gestations, method of delivery in relation to fetal presentation has little or no effect on neonatal mortality and subsequent neonatal neurodevelopmental outcome.


Prediction of light-for-gestational age at delivery in twin pregnancies: an evaluation of fetal weight deviation and growth discordance measured by ultrasound.

The purpose of this retrospective study was to evaluate and discuss different ultrasound methods widely used, among other things, as predictors for light-for-gestational age (LGA) in twin pregnancies. The methods evaluated and compared as predictors for LGA at birth were: (1) Difference between twins in biparietal diameter; (2) difference in abdominal diameter; (3) the percentage difference in estimated fetal weight between twins; and (4) estimation of the weight deviation from the expected weight during pregnancy. The study comprised 66 twin pregnancies, examined by ultrasound scanning less than 15 days before delivery. Using Relative Operating Characteristic curves (ROC curves) estimated fetal weight deviation was the most sensitive and specific of the methods. It is stressed that fetal discordance is not the appropriate predictor of LGA at birth in twin pregnancies.


Grand multiparity as an obstetric risk factor; a prospective case-control study.

In a socio-economically stable community with free access to medical care, a prospective comparison was made of pregnancy, delivery and neonatal data concerning 480 grand multiparas (> or = 5 deliveries) and 325 controls. The mean diastolic blood pressure was slightly higher (79.8 vs. 77.8 mmHg) among the grand multiparas and the rates of episiotomy differed greatly (5.8% in the grand multiparas vs. 45.7% in the controls). The main clinical difference was a slightly higher incidence of placental complications-i.e., praevia, abruptio and retentio (3.4% vs. 0.9%; P < 0.05) in the grand multiparas. The differences had no effect on neonatal outcome. Grand multiparity should be regarded as an obstetrical risk factor, mainly because of the higher frequency of placental complications. With good obstetric care there should be no adverse effects on the mother or the newborn.


The value of anamnestic information regarding previous genital infection in male fertility investigation.

The study was designed to assess the value of information from male subjects under fertility investigation, regarding previous genital infection, in clarifying the causes of depressed sperm quality. Information was gathered using a questionnaire which was sent to 312 men who had previously attended our laboratory for semen analysis. A previous sexual transmitted disease (STD) in the male partner did not significantly influence the sperm quality or the pregnancy rate. However, a previous STD in the female was generally associated with a lower pregnancy rate. Previous episodes with urethral discharge, dysuria, pain with ejaculation or suprapubic discomfort had little relevance for the subsequent sperm quality. The results indicate that, in general, information provided by men under fertility investigation, regarding previous genital infections or symptoms, is only of limited value in elucidating the cause of impaired sperm quality.


Plasma lipid and lipoprotein effects of transdermal administration of estradiol and estradiol/norethisterone acetate.

To evaluate the effect of transdermal sequential treatment with estradiol and estradiol/norethisterone acetate on lipoprotein metabolism, 25 postmenopausal women received treatment for 12 cycles of 4 weeks each (2 weeks estradiol 50 micrograms/day and 2 weeks a combined patch delivering norethisterone acetate 0.25 mg/day and estradiol 50 micrograms/day). Blood samples for lipoprotein analyses were drawn before treatment and in estrogen and combined phases in cycles 3 and 12. Plasma total cholesterol, low (LDL) and high (HDL) density lipoprotein were all significantly reduced in both estrogen and combined phases. Eighteen of the women continued the treatment for 36 cycles. In this group the HDL-cholesterol had returned to baseline values in combined phase in cycle 24. Plasma cholesterol and LDL-cholesterol values remained significantly reduced throughout the whole study compared to the pre-trial values. The present study by transdermal sequential hormonal treatment results in a lipid and lipoprotein pattern with reduced total cholesterol and LDL cholesterol in postmenopausal women.


Growth factor content in normal and benign ovarian tumours.

Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) content was measured in normal ovaries and benign ovarian tumours. Epidermal growth factor was present in 12.7% of normal ovaries, with a range 0.030-0.533 ng/mg DNA, and in 31.8% of benign ovarian tumours, with a range 0.1335-2.080 ng/ml DNA. TGF alpha was present in 84.5% of normal ovaries, with a range of values from 0.037-18.2 ng/mg DNA, and in 84.1% of benign ovarian tumours, with a range of 0.083-195 ng/mg DNA. The TGF alpha content in post menopausal benign ovarian tumours was significantly higher (P < 0.0001) than TGF alpha in the pre-menopausal normal ovarian group. The frequency of detection and levels of TGF alpha measured were significantly higher than those of EGF in the normal ovary group (P < 0.001) and also in the benign ovarian group (P < 0.005). We conclude that TGF alpha is the predominant growth factor present in normal ovaries and benign ovarian tumours.


Epidermal growth factor receptor in normal ovaries and benign ovarian tumours.

Epidermal growth factor receptor (EGFR) was assayed in 52 women who had normal ovaries removed at hysterectomy and in 30 women with benign ovarian tumours. The histology of each ovary was recorded. A single point screen was performed on all samples and in positive cases a full Scatchard analysis. EGFR was present in 8 of 52 normal ovaries (15.4%) and 3 contained the high-affinity component while 5 had the low affinity component. In the benign ovarian tumour group 4 of 30 tumours (13.3%) had receptor present, one was high affinity and 3 were low affinity in type. We can conclude that EGFR is detectable only at low frequency in normal and benign ovarian tumours.


A prospective randomized double-blind trial of ceftriaxone versus no treatment for abdominal hysterectomy.

The value of preoperative prophylactic parenteral treatment with ceftriaxone at elective abdominal hysterectomy was investigated in a prospective, randomized, double-blind study, in which 157 women participated, 77 in the antibiotic group and 80 in the control group. Increased febrile morbidity and a significant preponderance of women with urinary tract infections were observed in the untreated group, whereas there was no significant difference between the two groups regarding wound infections or infiltration at the top of the vagina. We find no indication for routine prophylactic use of antibiotics at elective abdominal hysterectomy.


Preoperative investigations for suspected pelvic masses.

Ultrasound examination was performed on 307 patients admitted to Herlev Hospital, Copenhagen, for suspicion of a pelvic tumor. Of these, 194 were operated on, 38 (19.6%) having a malignant tumor and 156 with benign conditions. A solid tumor was suspected in 72 patients on whom intravenous pyelography, barium enema, cystoscopy and rectoscopy were performed, although 11 did not undergo an intravenous pyelography and 12 did not undergo a barium enema. Intravenous pyelography, barium enema, rectoscopy and cystoscopy very seldom gave unsuspected information and never changed the indications for operation. Ultrasound examination of the kidneys, urinary tract, bowel system, liver and retroperitoneum as a complementary investigation to the gynecologic examination of the pelvic tumor gave the same information as did the barium enema, intravenous pyelography, rectoscopy and cystoscopy. Therefore, we conclude that these investigations should be carried out only in patients with symptoms from the urinary tract or the bowel system. Instead, we suggest that ultrasound examination of a pelvic mass also include an examination of the kidneys, urinary tract, bowel system, liver and retroperitoneum.


Comparison of five immunoassay procedures for the ovarian carcinoma-associated antigenic determinant CA 125 in serum.

Interassay variability in CA 125 values was studied in 77 serum samples (covering a range of CA 125 values between 8.9 and 310 arb. U/ml as measured by the original Centocor RIA) using three 125I-labeled RIA kits (Centocor, Byk and Cis) and two enzyme-labeled immunoassays (Abbott and Roche). Taking the Centocor RIA as a reference, orthogonal regression equations resulted in slopes varying between 0.74 and 1.35, with y-axis intercepts varying between -6.5 and +6.2, and correlation coefficients ranging from 0.88 to 0.94. Compared with the results of the Centocor RIA, the EIAs of Abbott and Roche gave overall lower CA 125 values, whereas the Cis and the Byk RIAs gave higher assay results. At the 35 arb. U/ml Centocor cut-off, serum levels with the other assays varied between 23 and 53 arb. U/ml. The 65 arb. U/ml cut-off level corresponded with CA 125 serum levels between 45 and 94 arb. U/ml. When classifying CA 125 values in three clinically relevant categories based on Centocor RIA results, ('normal' < or = 35 arb. U/ml, 'slightly elevated' > 35- < or = 65 arb. U/ml and 'elevated' > 65 arb. U/ml), discordances ranged from 26% with the Cis RIA to 40% utilizing the Byk RIA. The five CA 125 assays tested do not give equal assay results. As a consequence, the interpretation of CA 125 serum concentrations should be done with caution in disease monitoring and in the assessment of ovarian masses, especially when using different serum assays.


Ovarian carcinoma causing cerebellar degeneration.

Subacute cerebellar degeneration can be associated with malignancies. If the underlying tumor is a gynecological one, Purkinje cell cytoplasmic antibodies in serum serve as tumor markers.


Postpartum periarticular hip abscess with later coxitis caused by group B streptococcus.

Intrapartum haematogenous spread of vaginal group B Streptococcus is rare, but it can lead to severe complications like abscesses, endocarditis and meningitis postpartum. We report a postpartum periarticular hip abscess caused by group B Streptococcus. Clinically it caused pain in the hip and a compression of the femoral nerve with motor and sensory component. Diagnosis was made by aspiration under computed tomography control. The only sign of infection was an increased sedimentation rate. After antibiotic treatment the symptoms disappeared and the abscess vanished, but it was reactivated 4 months after delivery, leading to arthritis of the hip joint. Another antibiotic treatment was administered for 8 weeks. 17 months postpartum the patient is well, but a development of a secondary coxarthrosis can not be excluded.


Pulmonary complications of antepartum pyelonephritis: more alertness is needed.

Three cases of pulmonary complications associated with antepartum pyelonephritis are presented, in two of them tracheal intubation and mechanical ventilation were required. All three cases were related to recurrent urinary infections with failure of first line antimicrobial therapy and a concomitant usage of tocolytic therapy. The possible etiology, risk factors and clinical approach, aimed to prevent pulmonary complications in antepartum pyelonephritis are discussed.


Unsuspected involvement of the female genitalia in pemphigus vulgaris.

A 56-year-old woman had erosions due to pemphigus vulgaris in the inner thighs and perineum. The cutaneous lesions cleared following intramuscular gold therapy. However, because of complaints of dyspareunia, a colposcopic examination was performed and involvement of the cervix was demonstrated. The need for a vaginal examination in the monitoring of pemphigus vulgaris is emphasized.


Familial ovarian cancer.

Familial ovarian cancer occurs in approximately 5% of all ovarian cancers. Since the relation between ovarian cancer and genetic heritage has drawn much attention lately, general gynaecologists will more and more be faced with the question how to survey patients from a family with the familial ovarian cancer syndrome. We describe a patient from a family with three daughters, of which two older sisters were known to have ovarian cancer. Although our patient was closely observed, a third-stage ovarian cancer developed. With this case in mind and after a review of the literature, we will in future closely survey patients from familial ovarian cancer families from their twentieth birthday on, and recommend prophylactic bilateral oophorectomy after child-bearing age. However, we are aware of the fact that it is impossible to diagnose ovarian cancer in a premalignant phase as yet, and the benefit of a close survey might be an earlier diagnosis and not prevention. Also, prophylactic oophorectomy does not prevent the occurrence of intra-abdominal malignancies histopathologically indistinguishable from ovarian cancer. Patients should be aware of these restrictions. If, in the future, the precise chromosomal defect in ovarian cancer families is localized, prevention of ovarian cancer, but not of intra-abdominal malignancies of the same histopathology, might be within reach.


Alobar holoprosencephalic embryo detected via transvaginal sonography.

The incorporation of high-frequency transvaginal probes in commercial ultrasonic equipment allows now for the earlier detection of fetal malformations and the possibility of interrupting pregnancy when such an anomaly is incompatible with postnatal life. We describe here a case of alobar holoprosencephaly associated with serious facial anomalies, diagnosed via transvaginal sonography during the 10th week of amenorrhea. A cytogenetic study was carried out by transabdominal chorial biopsy and diagnostic confirmation by necropsy was made after termination. In order to be able to counsel patients on the advisability of future pregnancies we stress the importance of making a cytogenetic study of the embryo.


[Association of serum C3 and essential hypertension].

This study was performed to assess the possible involvement of humoral immunity in essential hypertension, independently of the presence of atherosclerotic disease, which in turn may be associated with immunologic changes. Sixty-five patients without demonstrated atherosclerotic disease were selected according to clinical and arteriographic criteria, including 23 hypertensive subjects (all pharmacologically treated) and 42 controls. Mean ages (58.7 +/- 8.3(1 S.D.) years in the controls and 57.7 +/- 7.9 years in the hypertensive subjects) and sex distribution were similar in the 2 groups. Of the main risk factors, atherosclerosis, smoking, diabetes, total cholesterol and HDL-cholesterol were equivalent, while triglycerides were higher in the hypertensive subjects than in the controls (142.6 +/- 52.7 vs. 112.6 +/- 67.7 mg/dl; p = 0.0065). In these subjects' sera the immunoglobulins IgG, IgA and IgM, and the third and fourth complement components (C3 and C4) were measured. Of these variables, only C3 was higher in the hypertensive subjects than in the controls (124.3 +/- 29.3 vs. 107.8 +/- 18.4 mg/dl; p = 0.0183). Furthermore, C3 was significantly correlated with triglycerides (tau = 0.3613; p < 0.0001), but the association with hypertension was confirmed only for C3, and not for triglycerides, by multiple logistic regression (p = 0.0142). The increase in serum C3 suggests the possible implication of humoral immunity in the pathogenesis or progression of essential hypertension.


[Inflammatory aneurysm of the abdominal aorta: anatomo-clinical study on 16 cases and pathogenetic hypothesis].

Inflammatory aneurysms of the abdominal aorta constitute an anatomoclinical entity characterised by prominent thickening and fibrosis of the aneurysmal wall, extending to the adjoining structures. Etiology, pathogenesis and relation with atherosclerosis still remain controversial. Sixteen consecutive patients undergoing surgery for inflammatory aneurysm of the abdominal aorta between March 1987 and December 1990 were studied (Group I); as a control, a series of 16 consecutive patients operated on in the same period for atherosclerotic aneurysm of the abdominal aorta was selected (Group II). As far as clinical history and symptoms are concerned, the comparison between the two groups revealed significant differences only for hydronephrosis (exclusively present in Group I, p < 0.05) and abdominal pain (more frequent in Group I, p < 0.01). The microscopic study of the aneurysmal wall was performed by scoring its histological features (atherosclerotic lesions, medial and adventitial fibrosis, inflammatory infiltrates and lymphatic stasis) from 1+ to 3+. As regards the microscopical features, atherosclerotic lesions were present in all the examined cases, whereas periadventitial fibrosis appeared in all the aneurysms of Group I and in none of Group II; the comparison between the two groups revealed further significant differences for extensive intimal calcification (exclusively present in Group II, p < 0.05), fibrous replacement of the tunica media (more thorough in Group I, p < 0.02), and the extent of inflammatory infiltrates (more prominent in Group I, p < 0.05). From the scarcity of pathognomonic features in both case-history and clinical presentation, the constant coexistence of prominent atherosclerotic lesions, and the progressive trend of the pathologic features, inflammatory aneurysms may be inferred to be a variant of atherosclerotic ones, characterised by a particular prominence of inflammation and fibrosis. The frequent occurrence of dilation of both periaortic lymphatic vessels and lymph node sinuses, even in "incipient" aneurysms, supports the hypothesis that it may be the lymphatic stasis which determines periaortic fibrosis. Finally, atherosclerotic components passing into periaortic fibrosis and eliciting granulomatous reaction were observed in two Group I cases featuring prominent "inflammatory" symptoms; such a finding favours the hypothesis that an immune reaction against some components of the atherosclerotic plaque may lead to the pronounced inflammatory response that is peculiar of inflammatory aneurysms.