The prognostic value of hypocholesterolemia in hospitalized patients

Clinical observations show that severe illness often leads to hypocholesterolemia. To verify this finding and to define the relationship between serum cholesterol and a patient's prognosis, a study was conducted in two large hospital populations. Of 24,000 and 61,463 adult patients (populations I and II) an average of 3.8% and 3.6% died in hospital, respectively. The mean serum cholesterol levels of patients who died was significantly lower than that of those who survived (163.6 mg/dl versus 217.8 mg/dl;P < 0.0001). The average cholesterol of surviving patients was similar to that of 6,543 healthy controls. During hospitalization serum cholesterol levels of 100 mg/dl were encountered in 1.2% and 3.6% of patients of populations I and II, respectively. The mortality of these hypocholesterolemic patients was about tenfold higher than average and showed a strong, inverse, linear relationship with serum cholesterol concentrations. Patients whose serum cholesterol level dropped to less than 45 mg/dl did not survive. These data show that in severely ill patients serum cholesterol may decline to very low concentrations, and the prognosis is reflected by the degree of hypocholesterolemia, which thus may serve as a clinically useful prognostic parameter. Correspondence to: E. Windler     

Molecular analysis of <Emphasis Type="Italic">Fiji disease virus</Emphasis> genome segments 5, 6, 8 and 10

Summary. The complete sequences of Fiji disease virus (FDV) genome segments 5 (S5), S6, S8 and S10 were obtained and comprised 3150nt, 2831nt, 1959nt and 1819nt, respectively. Each segment contained a single ORF which encoded putative proteins of 115kDa, 97kDa, 69kDa and 63.0kDa, respectively. The putative amino acid sequences encoded by S5 and S6 contained putative leucine zipper motifs while FDV S5 and S8 each contained an ATP-GTP-binding motif. At the amino acid level, FDV S5, S6, S8 and S10 showed most similarity to the corresponding segments of Rice black-streaked dwarf virus. Based on sequence similarities, it is predicted that FDV S8 encodes a minor core protein, while FDV S10 encodes an outer capsid protein. The evolutionary relationships of FDV to other reoviruses are discussed.The nucleotide sequence data for FDV S5, S6, S8 and S10 are available in the DDBJ/EMBL/GenBank databases under the accession numbers AY029521, AF356083, AY297693 and AY297694, respectively.     

Factors influencing serum neopterin and β2-microglobulin levels in a healthy diverse population

Sera and questionnaire data from a population-based random sample of healthy adults was used to evaluate factors influencing neopterin and 2-microglobulin (2m) values. Both neopterin and 2m levels increased with age and were higher among white than blacks (mean values for whites and blacks: neopterin, 5.06 vs 4.49 nmol/L; 2m, 1.36 vs 1.28 mg/L). Gender differences were noted for 2m but not neopterin values (2m males vs females: 1.37 vs 1.29 mg/L). Neopterin values were lower among current smokers than among nonsmokers (4.32 vs 5.16 nmol/L) and were higher among users of antihistamines (5.46 among users vs 4.65 nmol/L among nonusers). Neopterin and 2m were correlated in this healthy adult population (adjustedr=0.53,P=0.001), yet no other interrelationships with numerous biologic markers except between 2m and serum-soluble interleukin-2 receptor levels (adjustedr=.41,P=0.05) were observed. These findings provide important baseline information to consider before planning or evaluating studies utilizing neopterin or 2m levels.     

Fibrinogen levels in hypercholesterolemic smokers and non-smokers in relation to age and gender

Abstract. Elevated total cholesterol and plasma fibrinogen levels and smoking are risk factors for cardiovascular disease, whose inter-relationships are influenced by both gender and age. The aim of this study was to investigate the effect of smoking on fibrinogen levels in a hypercholesterolemic population subdivided on the basis of gender and age. The study included 492 hypercholesterolemic subjects, divided into four subpopulations: men and women, aged 26–49 and 50–66 years. Mean fibrinogen levels among smokers and non-smokers in the four subpopulations of this hypercholesterolemic cohort followed mean total cholesterol levels. Three subpopulations (men <50 years, men 50 years and women 50 years) showed differences in mean total cholesterol and fibrinogen values between smokers and non-smokers (total cholesterol 7.23±0.54 vs. 7.40±0.93 mmol/l and fibrinogen 2.79±0.48 vs. 3.23±0.72 g/l in men <50 years; total cholesterol 7.17±0.43 vs. 7.50±0.60 mmol/l and fibrinogen 3.11±0.44 vs. 3.68±0.66 g/l in men 50 years and 7.41±0.59 vs. 7.65±0.73 mmol/l and fibrinogen 3.29±0.61 vs. 3.58±0.71 g/l in women 50 years). These values correspond to a percentage difference between smokers and nonsmokers in total cholesterol and fibrinogen of 2.4% and 15.8% in men <50 years, 4.6% and 18.3% in men 50 years and 3.2% and 8.8% in women 50 years. All differences were significant (P<0.05), except for total cholesterol in the younger men (<50 years). No differences between smokers and non-smokers were observed in the younger female group (<50 years). Except in the younger female group (<50 years), significant differences between smokers and non-smokers were also observed in the number of subjects exceeding the upper reference value of fibrinogen (>4.0 g/l), the highest percentage being found for the older women smokers (50 years) (29%). In Conclusion, smoking elevates fibrinogen levels in hypercholesterolemic men (<50 years; 50 years) and older women (50 years), but not in younger women (<50 years).     

Plasma lipids and lipoproteins and essential hypertension

In recent years there have been many studies demonstrating a correlation between increased arterial blood pressure and altered lipid profiles, and there has been an especially positive correlation between high cholesterol levels and blood pressure. There are differences between the various reports that are important. In our study the lipid distribution in 105 hypertensive patients with mild or moderate arterial hypertension according to WHO criteria without clinically or ultrasonographically apparent atherosclerosis was compared to the lipid distribution in 65 age-matched healthy persons. On the epidemiological level a significant, positive association was found between LDL serum levels (P 0.001), Apo B serum levels (P 0.001), serum triglyceride levels (P 0.05) and VLDL serum levels (P 0.01) and arterial hypertension. However, in contrast to recent reports, no significant difference was found between total serum cholesterol levels in normotensives and hypertensives, and there was no difference in HDL serum levels. No evidence could be found for a significant increase in lipoprotein (a) serum levels in hypertensives.Abbreviations LDL low density lipoprotein - VLDL very low density lipoprotein - HDL high density lipoprotein - Apo B 100 apolipoprotein B 100 - Apo A I apolipoprotein A I Correspondence to: H. Vetter     

Combination therapy of cyclosporine with steroid inhibits γ-interferon and interleukin-1 gene expression at the level of mRNA synthesisin vivo

The present study examined the effect of cyclosporine (CsA) administered with steroidin vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to generate cytokines and their gene expression at the level of messenger RNA (mRNA). PBMC from CsA-prednisolone (Pred)-treated recipients displayed 66.9% inhibition (54.3±12.4 IU/ml;N=42;P<0.01) of -interferon (-IFN) production compared with normal individuals (134.6±18.6 IU/ml;N=23). Azathioprine (Az)-Pred-treated recipients displayed significantly less inhibition of -IFN generation (96.0±16.1 IU/ml;N=22;P<0.05) than CsA-treated patients. Macrophages (m) from CsA-Pred-treated recipients displayed 60.0% inhibition (5.1±0.7 U/ml;N=20;P<0.01) of interleukin-1 (IL-1) production compared with normal individuals (13.0±2.9 U/ml;N=21). These results were confirmed by the experiments using cDNA probe for -IFN or IL-1 (, ). High levels of -IFN mRNA in phytohemagglutinin (PHA)-stimulated PBMC or IL-1() mRNA in lipopolysaccharide (LPS)-stimulated m were present in normal individuals but not in CsA-treated recipients as judged by hybridization to a cloned human -IFN or IL-1() cDNA probe. These studies demonstrated that combination therapy of CsA with steroid inhibits both -IFN and IL-1 gene expression at the level of mRNA at physiological concentrations.     

Analysis of synovial fluid from clinically healthy Iranian fat-tailed sheep

In this study synovial fluid from the radiocarpal joints of 100 clinically healthy Iranian sheep (Lori-Bakhtiari) were analyzed. Total nucleated cell count (TNCC) of the synovial fluid was 178.9±75 cells/l (mean±SD). Lymphocytes were the predominant cell type composing 48.34±17.2% of the cells found in the synovial fluid, whereas monocytes, macrophages and neutrophils composed 36.52±3.5%, 12.75±5.9% and 2.28±1.18% of the cells found in the synovial fluid, respectively. The glucose concentration of synovial fluid was 44.9±9 mg/dl. The concentration of total protein, albumin and globulin of the synovial fluid were 2.31±0.55, 1.49±0.38, 0.81±0.28 g/dl, respectively. The albumin to globulin ratio (A/G) was 2.02±0.61. Age and sex had no significant effects on TNCC, percentage of lymphocytes, monocytes, macrophages and neutrophils, concentration of total protein, albumin, globulin, and A/G ratio of fluid from the radiocarpal joint. However, glucose concentration in radiocarpal fluid in sheep less than 1-year-old was significantly (P0.05) higher (48.27±1.4 mg/dl) than 1- to 2-years-old (42.1±1.4 mg/dl) and more than 2-years-old sheep (43.9±1.8 mg/dl). No significant differences were found between right and left limbs for any parameters evaluated in this study.     

In vitro activity of saperconazole (R66 905) compared with amphotericin B and itraconazole againstAspergillus species

Twenty isolates of aspergillus were tested against saperconazole and 16 of these against itraconazole and amphotericin B using a macrodilution broth method. For 18 (90 %) of 20isolates tested against saperconazole, MICs were 3.1 mg/l and for 15 (75 %) of 20 isolates MFCs were 3.1 mg/l. For 9 (56 %) of 16 isolates tested against itraconazole, MICs were 3.1 mg/l, and for 4 (33 %) of 12 isolates MFCs were 3.1 mg/l. For all 16 isolates tested against amphotericin B MICs and MFCs were 4.0 mg/l; for 11 of 16 isolates MICs were 2.0 mg/l. Saperconazole appears to be highly active againstAspergillus spp. in vitro, with a bimodal distribution of MICs and MFCs.     

Behavior of soluble HLA class I antigens in patients with chronic hepatitis C during interferon therapy: An early predictor marker of response?

Soluble HLA class I antigens (sHLA-I), ₂-microglobulin ( ₂-.) and alanine aminotransferase (ALT) serum levels have been evaluated in 16 patients affected by chronic hepatitis C treated for six months with recombinant interferon- (rIFN-, 3 MU three times a week). The predictor role of sHLA-I and ALT modifications with respect to the response to rIFN- therapy was also evaluated. Six patients responded (group 1), five patients relapsed following an initial response (group 2), and five did not respond to rIFN- treatment (group 3). The baseline serum levels of sHLA-I and ₂- were significantly higher in all three groups of HCV-positive patients with respect to HCV-negative controls (P<0.05). A significant increase of sHLA-I serum level with respect to baseline value (P<0.001) was observed in group 1 patients after two weeks of rIFN- treatment. sHLA-I serum level then decreased, although remaining steadily and significantly increased with respect to baseline (P values ranging from 0.05 to 0.01) in the following five months and then returned to baseline one month after the end of rIFN- administration. No significant variations of ₂- serum levels were detected throughout the observation period. In group 1 patients ALT serum levels significantly decreased after two weeks of rIFN- treatment (P<0.001) and then remained in the normal range throughout the observation period. In the other two groups of patients no relevant variations of sHLA-I and ₂- serum levels were found during and after rIFN- therapy. The modifications of sHLA-I serum levels discriminate, as a single marker, group 1 patients from group 2 and 3 patients after two weeks of rIFN- treatment (P<0.003). The association of sHLA-I and ALT modifications improves the discriminant power and leads to a complete differentiation of the three groups of patients after four weeks of rIFN- treatment (P<0.0001). If confirmed in a larger series of patients, these results will provide a useful marker to predict which patients affected by chronic hepatitis C will respond to treatment and will help to avoid their ineffective treatment with an expensive and potentially harmful drug.     

Biometrical characteristics and physiological responses to a local cold exposure of the extremities

The aim of this study was firstly to describe the physiological responses observed in 19 subjects during immersion of the arm up to the elbow in water at 5 °C (5 min) followed by a 10-min recovery and secondly, to correlate the observed physiological responses with biometrical characteristics of the subjects (maximal oxygen uptake, VO_2max, percentage fat content of whole body, BF, and arm, forearm and hand skinfold thickness). The results showed that the time courses of changes in forearm and hand skin temperature were different compared to those of finger skin temperatures both during local cooling and during rewarming (P < 0.05). Cardiovascular responses (heart rate, systolic and diastolic blood pressures) and finger skin temperatures were not related to the biometrical characteristics of the subjects. However, at the end of the immersion, decreased hand skin temperature was correlated to VO_2max (r = 0.45, P 0.05) whereas decreased forearm skin temperature was correlated both to VO_2max (r = 0.44, P 0.05) and to skinfold thickness (r = –0.44, P 0.05) but not to BF. During the beginning of the recovery period only, outside, inside forearm and hand skin temperatures were related to VO_2max (r = 0.54, P 0.05; r = 0.66, P 0.01 and r = 0.45, P 0.05, respectively) and all the skinfold thicknesses (r = –0.47 to –0.71, P 0.05). It was concluded that the local skin temperature profiles differed according to the upper limb segment both during cooling and during early rewarming. Moreover, VO_2max and upper limb skinfold thickness but not BF did influence the forearm and hand skin temperature changes during cooling and early rewarming but not the finger skin temperature changes and cardiovascular responses.     

Treatment of coronary heart disease by diet and exercise: Fasting and diurnal lipoproteins

Summary The effects of a combined exercise and low-fat dientary regimen were studied in 11 patients with angiographically documented coronary heart disease (cholesterol 233 mg/dl, triglycerides 158 mg/dl) and 13 comparable patients (cholesterol 224 mg/dl, triglycerides 174 mg/dl) on usual care. During one year, fasting serum lipoproteins were lowered to ideal levels in the intervention group (cholesterol 191 mg/dl, triglycerides 100 mg/dl, LDL-cholesterol 121 mg/dl). There was no change of triglycerides and cholesterol on usual care while LDL-cholesterol rose significantly. Neither regimen had any effect on HDL-cholesterol. Diurnal triglycerides as a presumptive measure of IDL in the intervention group were diminished by 39%. The study demonstrates the feasibility of a diet and exercise regimen to normalize midly elevated plasma lipid levels and thus to possibly affect the course of coronary heart disease without drugs.Abbreviations Chol cholesterol - TG triglycerides - HDL high density lipoproteins - LDL low density lipoproteins - LP(a) lipoprotein (a) - P/S polyunsaturated to saturated fatty acid ratio - Int. Intervention group - C Control group Supported by Bundesministerium für Forschung und Technologie     

Immunohistochemical studies on S-100 cells in the anterior pituitary gland of Sprague Dawley rats and spontaneous dwarf rats

The S-100 cells in the pituitary glands of adult male Sprague Dawley rats (SDs) and spontaneous dwarf rats (SDRs) were immunohistochemically examined using anti-S-100 and anti-S-100 monoclonal antibodies. The immunoreactive cells against S-100 protein were divided into three subtypes on the basis of their immunore-activity against subunits of S-100 protein: S-100 dominant type (the -type cell), S-100 dominant type (the \-type cell) and immunoreactive against both S-100 and S-100 (the -type cell). In the SD, -type cells represented 26% of the total S-100 immunoreactive cells (S-100 cells) and were localized in the peripheral area of the ventral region of the pituitary gland. This type of cell was observed forming clusters, with more abundant cytoplasm than the -type cell. The proportion of -type cells was 53%. They were diffusely distributed throughout the gland, and their processes were thicker than those of the -type cell. In the SDR, the proportion of -type cells was 55%, and they were observed throughout the gland. In contrast, -type cells totalled 12% and were localized in small areas of the central and peripheral region of the gland. The proportion of -type cells was 21% in the SD and 33% in the SDR and they were observed forming small clusters in both animal groups. The proportion of -type cells compared with the total of S-100-immunoreactive cells was significantly higher (P < 0.05) in the SDR than in the SD, while the proportion of -type cells was markedly lower (P < 0.05).     

Changes in the susceptibility ofBacteroides fragilis group organisms to various antimicrobial agents 1979–1989

The in vitro activity of metronidazole, chloramphenicol, clindamycin and 11 -lactam antibiotics against 135 clinical isolates of theBacteroides fragilis group was compared. In addition, changes in the resistance patterns of members of theBacteroides fragilis group isolated at the Hospital Universitario San Carlos in Madrid, Spain, between 1979 and 1989 were documented. The most active -lactam drugs were imipenem and -lactamase inhibitor combinations. In 1989, however, two strains were found to be resistant to imipenem and to all other -lactam agents tested. There was no emergence of resistance to metronidazole. Chloramphenicol was very effective: only one resistant strain was detected in 1979 and no chloramphenicol-resistant isolates were found during the rest of the study period. An outbreak of clindamycin resistance was noted in 1982, and the first cefoxitin resistant strains were recovered in 1985. The changing patterns of susceptibility of anaerobic bacteria to antimicrobial agents and the emergence ofBacteroides fragilis strains resistant to new -lactam agents suggest that periodic antimicrobial susceptibility tests should be performed in order to guide the selection of antimicrobial agents for therapy.     

Measurement precision of a portable instrument to assess vibrotactile perception threshold

Summary The objective of the present study was to evaluate the reliability of a modified version of the commercially available Biothesiometer, and to examine vibrotactile perception thresholds with respect to age and gender. A standardized protocol for measuring vibrotactile perception threshold was administered to 80 subjects, once a week over 4 weeks. Inter-session variability was stable (analysis of variance for repeated measures; P>0.05) and correlations were high (Pearson's: 0.87r0.90; P0.001). For sites on both hands and feet, there was a significant increase with age (0.19r ²0.52; P0.001). Five factor analysis of variance model showed that vibrotactile perception threshold was significantly different with stimulus site, age category and gender; no differences were observed with alcohol consumption or smoking status. The findings indicate that the measurements from this device are highly reproducible and sensitive to expected threshold differences with age and gender. The authors attribute this to technical improvements of the original apparatus, rigid adherence to test protocol and maintenance of standard conditions. This type of instrument would be useful in assessing vibrotactile perception loss in occupational health studies.     

Hyperhomocysteinemia and the response to vitamin supplementation

Summary The long-term vitamin requirements of men (n=22) with moderate hyperhomocysteinemia (plasma total homocysteine concentration > 16.3 mol/1) were investigated over a period of 48 weeks. An initial 6-week period of vitamin supplementation (1.0 mg folic acid, 10 mg pyridoxine, 0.05 mg cyanocobalamin) reduced plasma homocysteine levels 54.7% (P<0.001). However, 18 weeks after vitamin therapy was discontinued, only seven participants (subgroup A) still had plasma homocysteine levels of 16.3 mol/l or lower. The remainder of the participants (subgroup B) required a second 6-week period of vitamin therapy to normalize the elevated plasma homocysteine levels. Substitution of vitamin supplementation by dietary guidelines to increase folate intake from food products failed to maintain normal plasma homocysteine levels in participants from subgroup B. Long-term vitamin supplementation may be required in some individuals to prevent hyperhomo-cysteinemia.Abbreviations HPLC high-performance liquid chromatography - Lp(a) lipoprotein(a) - PLP pyridoxal 5-phosphate     

Scanning electron microscopy of merogonous stages ofEimeria falciformis var.pragensis inMus musculus

Asexual stages ofEimeria falciformis var.pragensis in Swiss-Webster mice were studied by scanning electron microscopy. Sporozoites were present in the cecum and colon 2 h post-inoculation (PI) and measured 11.3×2.1 m (9–13.9×2–2.2 m). Sporozoites penetrated epithelial cells with an extended anterior end and were constricted at the site of entry. Asexual generations were found in the cecum and colon epithelial cells. In meronts found at days 3–6 PI, merozoites matured synchronously, were oriented in the same direction, and were arranged in a helical pattern. Such meronts measured 11.3×6.4 m (8–13.7×5–7.4 m) and contained 8–12 meroxoites, which measured 11.9×1.5 m (7.4–15.7×1.3–1.8 m). Meronts which were present at day 7 PI measured 9.5×8.2 m (9–10.5×7–9.5 m) and contained 20–50 small merozoites which budded asynchronously from a central residuum. At days 3–7 PI, parasitized epithelial cells had shorter and fewer or no microvilli. The lumenal plasmalemma of the host cell was often disrupted or absent in cells containing mature meronts and escaping merozoites. At day 6 PI, phagocytic cells appeared on the epithelial surface, some of which were in contact with merozoites. Small foci of exposed basal lamina were present at day 7 PI in areas where cells had sloughed from the epithelium.     

Y-intercept of the maximal work-duration relationship and anaerobic capacity in cyclists

The degree to which the y-intercept (Y-int) of the linear regression of maximal work output on exercise duration represented anaerobic capacity was determined in ten well-trained male cyclists [peak oxygen uptake ( = 69.8 (SD 4.2) ml · kg ^–1 · min ^–1). Each cyclist performed three exhausting cycle sessions on separate occasions; the mean exercise durations were 312, 243 and 141 s for the low (approximately 104% , medium (approximately 108% and high (approximately 113% intensities respectively, and Y-int (kilojoules; joules per kilogram was derived from the regression of work output on exercise duration. The muscle anaerobic adenosine 5-triphosphate (ATP) yield (ATP) and anaerobic capacity (AC) were estimated from changes in metabolites in the vastus lateralis muscle and blood lactate concentration during the high intensity cycling session. The activities of glycogen phosphorylase, phosphofructokinase and citrate synthase, as well as muscle buffer value (in vitro ) were also determined. The Y-int (kilojoules) was positively correlated (P0.05) with AC (r=0.73), ATP (r=0.70) and in vitro (r=0.71); similar correlations (P0.05) were observed for Y-int (joules per kilogram). The Y-int was not correlated (P>0.05) with any enzyme activity. When the Y-int was transformed into oxygen equivalents [litres of oxygen equivalent (1 O₂ Eq)] it was, on average, 0.92 1 O₂ Eq lower than AC (P0.05); however, an alternative method of establishing the work-duration regression yielded a mean Y-int which was only 0.19 1 O₂ Eq less than AC (P0.05). These findings support the validity of Y-int as a work estimate of anaerobic capacity in well-trained cyclists.     

Dissemination in five French hospitals ofKlebsiella pneumoniae serotype K25 harbouring a new transferable enzymatic resistance to third generation cephalosporins and aztreonam

A strain ofKlebsiella pneumoniae K25 resistant to newer-lactam drugs was isolated in clusters in five hospitals in the Paris area. The MICs of ceftazidime and aztreonam (128 mg/l) were higher than that of cefotaxime (16 mg/l) for the strain but when measured in the presence of clavulanic acid, they were 1 mg/l. The donor strains and derivatives produced a-lactamase with a pI of 7.75–7.8 and hydrolysing activity against a wide spectrum of-lactams similar to that of SHV-2 and SHV-3, but with significant hydrolysis of ceftazidime. This new enzyme could be designated SHV-4.     

Roles of inositol trisphosphate and protein kinase C in the spontaneous outward current modulated by calcium release in rabbit portal vein

We examined the effects of heparin, guanosine nucleotides, protein kinase C (PKC) modulators, such as phorbol 12,13-dibutylate (PDBu) and H-7 on Ca²⁺-dependent K⁺ currents in smooth muscle cells of the rabbit portal vein using the whole-cell patch-clamp technique, to explore the effects of PKC on the oscillatory outward current (I _oo). Neomycin (30 M), an inhibitor of phospholipase C, and intracellular applications of heparin (10 g/ml) and guanosine 5-O-(2-thiodiphosphate) (GDP[S]; 1 mM) partly but consistently inhibited the generation of I _oo, whereas a higher concentration of heparin (100 g/ml) transiently enhanced then suppressed the generation of I _oo. Inhibition of I _oo generation by heparin was more powerful at the holding potential of + 20 mV than at –20 mV. Inositol 1,4,5-trisphosphate (InsP ₃; 30 M) continuously generated I _oo at holding potentials more positive than –60 mV. Noradrenaline (10 M) and caffeine (3–20 mM) transiently augmented, then reduced the generation of I _oo. Heparin (10 g/ml) completely inhibited responses induced by InsP ₃ and noradrenaline, but not those induced by caffeine. Intracellular application of guanosine 5-triphosphate (GTP; 200 M) or low concentrations of guanosine 5-O-(3-thiotriphosphate) (GTP[S]; 3 M) continuously augmented the generation of I _oo. High concentrations of GTP[S] (10 M) transiently augmented, then inhibited I _oo. Neither GTP[S] nor noradrenaline induced the transient augmentation or the subsequent inhibition of I _oo when applied in the presence of GDP[S] (1 mM), neomycin (30 M) or heparin (10 g/ml). PDBu (0.1 M) reduced the generation of I _oo but failed to produce an outward current following application of caffeine (3–5 mM). This action of PDBu was inhibited by pretreatment with H-7 (20 M). In the presence of H-7, GTP[S] continuously enhanced the generation of I _oo. The suppression of the generation of I _oo during application of noradrenaline (10 M) was reduced by pretreatment with H-7. Thus both InsP₃ and protein kinase C contribute to the generation of I _oo in smooth muscle cells of the rabbit portal vein and heparin is not a specific InsP ₃ antagonist on the InsP ₃-induced Ca²⁺-release channel (PIRC). InsP ₃ opens PIRC and protein kinase C may deplete the stored Ca²⁺ by either inhibiting the reuptake of Ca²⁺ or by enhancement of the releasing actions of InsP ₃.     

Papillary cystic tumours of the pancreas: An analysis by nuclear morphometry

Papillary cystic tumour (PCT) is a rare, low-grade malignant pancreatic neoplasm, in which the histological criteria for malignancy are still uncertain. We performed a histological examination of 3 metastasizing PCTs, while comparing them with 18 non-metastasizing PCTs, using a computed image analyser. The mean maximum nuclear diameter, the mean standard deviation (SD) of the nuclear diameter, the mean nuclear area and the nuclear-nonnuclear (N/NN) ratio obtained by the image analyser of the metastasizing PCTs (7.23 m, 2.21 m, 30.45 m², 36.41%) were all significantly larger than those of the non-metastasizing PCT (6.34 m, 1.59 m, 23.66 m², 23.74%;P<0.005,P< 0.005,P<0.005,P<0.001 respectively). However, there were no statistical differences in either the nuclear ellipsoidity or nuclear regularity. These results suggested that nuclear morphometry might be a useful parameter to define metastatic potential, in addition to histological variables such as venous invasion, nuclear grade and mitotic rate.