Perioperative complications after aorto-iliac stenting: associated factors and impact on follow-up cardiovascular prognosis.

OBJECTIVES: To investigate factors associated with 30-day perioperative complications (POC) after aorto-iliac (AI) stenting, and to compare follow-up cardiovascular prognosis between patients with and without POC. MATERIALS AND METHODS: This was a retrospective multicenter study. We used a multicenter database of 2012 consecutive patients who successfully underwent AI stenting for peripheral arterial disease in 18 centers in Japan from January 2005 to December 2009 to analyze independent predictors of POC and impact of POC on prognosis by logistic regression and a Cox proportional hazard regression model, respectively. RESULTS: Mean age was 71 ± 9 years (median: 72 years; range: 37-98 years), and 1,636 patients (81%) were men. POC occurred in 126 patients (6.3%). In multivariate logistic regression analysis, old age (≥80 years), critical limb ischemia (CLI), and Trans Atlantic Inter-Societal Consensus (TASC) II class C/D were independently associated with POC with adjusted odds ratios and 95% confidence intervals (CI) of 1.9 (1.3-2.9), 2.3 (1.5-3.4), and 2.4 (1.6-3.4), respectively. Out of 2012 patients, 1995 were followed up for more than 30 days (mean: 2.6 ± 1.5 years; range: 2-2,393 days). In a Cox hazard regression model adjusted for baseline clinical characteristics, POC was positively and independently associated with follow-up major adverse cardiac events (adjusted hazard ratio [HR]: 1.9; 95% CI: 1.3-2.8; p = .002), but not with major adverse limb events and target lesion revascularization (adjusted HR: 1.4; 95% CI: 0.7-2.7; p = .25; and adjusted HR: 1.2; 95% CI 0.6-2.6; p = .568), respectively. CONCLUSIONS: Age >80 years, CLI, and TASC C/D lesion were positively associated with POC after AI stenting. Occurrence of POC appears to adversely affect follow-up cardiovascular, but not limb and vessel prognosis.

Trans-collateral angioplasty for the treatment of long chronic total occlusions of superficial femoral arteries: a novel wiring technique.

Endovascular therapy (EVT) utilizing percutaneous transluminal angioplasty has become a standard technique to re-establish sufficient blood flow in ischemic limbs of patients with peripheral arterial disease (PAD). Long chronic total occlusion (CTO) of the superficial femoral artery (SFA) remains one of the challenging lesions in the field of EVT for PAD patients, despite the recent introduction of many dedicated interventional devices such as high-performance guidewires. In this article, we report a novel interventional technique, trans-collateral angioplasty (TCA), to improve the initial success rate of EVT for long SFA-CTO lesions. We present one representative case, and describe the technical tips and appropriate device selection criteria for the TCA procedure. The outcomes of TCA for long SFA-CTO performed last year at our institution are also summarized and discussed.

Regulation of the coronary vasomotor tone: What we know and where we need to go.

The control of coronary blood flow has been studied for decades, but despite our extensive efforts, the critical regulators of flow are largely unknown. One purpose of this review is to summarize some recent concepts about the control of coronary flow and also point out areas where additional knowledge must be acquired. A second purpose of this review is to highlight the need for additional noninvasive measurements of flow that undoubtedly will require further evolution of contemporary technologies, and also application of specific methods toward noninvasive measurements of coronary blood flow. Only after the development of such measurements will the scientific community begin to understand the intricacies of the regulation of coronary flow in human beings.

[Survey of vaccination for physically-handicapped and epileptic children].

We studied immunization for 128 handicapped patients, from 3 to 15 years of age, in a Seishi Gakuen Hospital, with 8 vaccines: diphtheria-purified acellular pertussis-tetanus combined (DPT), BCG, polio, measles, rubella, mumps, varicella, and Japanese B encephalitis. The rate of vaccination in these patients was lower than in healthy children at 3 years of age in Kanazawa City. There was no significant difference between patients with and without epilepsy. The rate was higher in the hospitalized patients than in the outpatients. More than 90% of the hospitalized patients was immunized against influenza under informed consent in 1997 and 1998. Despite pandemics of influenza in Kanazawa City, where the hospital was located, the period of fever by influenza was significantly shorter in our patients in both 1997 and 1998 than in 1996. Although a half of our patients had epilepsy, they were safely vaccinated with few side effects.

Role of pertussis toxin-sensitive G protein in metabolic vasodilation of coronary microcirculation.

We have previously demonstrated that pertussis toxin (PTX)-sensitive G protein (G(PTX)) plays a major role in coronary microvascular vasomotion during hypoperfusion. We aimed to elucidate the role of G(PTX) during increasing metabolic demand. In 18 mongrel dogs, coronary arteriolar diameters were measured by fluorescence microangiography using a floating objective. Myocardial oxygen consumption (MVO(2)) was increased by rapid left atrial pacing. In six dogs, PTX (300 ng/ml) was superfused onto the heart surface for 2 h to locally block G(PTX). In eight dogs, the vehicle (Krebs solution) was superfused in the same way. Before and after each treatment, the diameters were measured during control (130 beats/min) and rapid pacing (260 beats/min) in each group. Metabolic stimulation before and after the vehicle treatment caused 8.6 +/- 1. 8 and 16.1 +/- 3.6% dilation of coronary arterioles <100 microm in diameter (57 +/- 8 microm at control, n = 10), respectively. PTX treatment clearly abolished the dilation of arterioles (12.8 +/- 2. 5% before and 0.9 +/- 1.6% after the treatment, P < 0.001 vs. vehicle; 66 +/- 8 microm at control, n = 11) in response to metabolic stimulation. The increases in MVO(2) and coronary flow velocity were comparable between the vehicle and PTX groups. In four dogs, 8-phenyltheophylline (10 microM, superfusion for 30 min) did not affect the metabolic dilation of arterioles (15.3 +/- 2.0% before and 16.4 +/- 3.8% after treatment; 84.3 +/- 11.0 microm at control, n = 8). Thus we conclude that G(PTX) plays a major role in regulating the coronary microvascular tone during active hyperemia, and adenosine does not contribute to metabolic vasodilation via G(PTX) activation.

Presence of Turner stigmata in a case of dysgenetic male pseudohermaphroditism with 45,X/46,X+mar karyotype.

A case is reported of dysgenetic male pseudohermaphroditism (DMPH) having Turner stigmata and 45,X/46,X+mar karyotype. The marker chromosome of this patient consisted of most if not all of the short arm, including the sex determining region of the Y chromosome. Although this karyotype is relatively common in Turner's syndrome and occasionally observed in mixed gonadal dysgenesis, DMPH is usually exemplified by a 46,XY karyotype except for one patient reported with 45,X/46,XY mosaicism. Turner stigmata have not previously been reported in DMPH. The present patient is an intermediate case between mixed gonodal dysgenesis and typical DMPH, and this indicates that 45,X/ 46,X +mar karyotype abnormality can result in a wide range of phenotype such as DMPH, mixed gonodal dysgenesis and Turner's syndrome.

[Composition of HIV-1 B-epitopes and heterologous T-cell epitopes. I. Maintenance of antigenic properties of HIV-1 B-epitopes]. / Kompzitsii iz B-épitopov VICh-1 i geterologichnykh T-kletochnykh épitopov. I. Sokhranenie antigennykh svoistv B-épitopov VICh-1.

Peptides were synthesized combining an immunodominant B-cell epitope from gp41 of HIV-1 with heterogenous T-cell epitopes from tetanus toxoid or hepatitis B core antigen with no spacer bridge between epitopes. The antigenic properties of the B-cell epitope within the composites were evaluated. The majority of the rabbit sera against the immunodominant B-cell epitope from gp41 recognized the B-cell epitope of gp41 and its composites as closely related structures. The comparative study of the composite peptide recognition by HIV-1 antibody positive human sera revealed that 82% of them similarly recognized a single gp41 epitope and its composites. The difference in the affinity values for the B-cell epitope from gp41 and its composites was less prominent than the difference between the affinity values for the single peptides derived from the immunodominant region of gp41. This indicates that the B-cell epitope from gp41 was not changed by fusion to heterologous amino acid sequences. The evaluation of the immunogenicity of the composites would reveal whether the antigenic characteristics can be of help in the selection of the components of multivalent peptide vaccines.

Central hypothyroidism resulting from pituitary suppression and peripheral thyrotoxicosis in a premature infant born to a mother with Graves disease.

We observed the sequential changes in serum thyroid hormones and thyroid-stimulating hormone receptor antibodies in an infant born at 30 weeks of gestation to a mother with florid Graves disease. Transient central hypothyroidism caused by pituitary suppression was observed after the resolution of peripheral thyrotoxicosis induced by thyroid-stimulating antibody. Central hypothyroidism became overt when the suppression of the pituitary gland after fetal thyrotoxicosis was combined with weak activity of thyroid-stimulating antibody after birth.

A case of pseudo-Bartter's syndrome due to intestinal malrotation.

Intestinal malrotation presenting beyond the neonatal period is associated with a multiplicity of symptoms, which are often non-specific and, consequently, are associated with delays in diagnosis. Pseudo-Bartter's syndrome, which mimics the manifestations of Bartter's syndrome, can be caused by a severe chloride deficiency secondary to vomiting, diarrhea, perspiration, diuretic abuse and so on. We describe a 6 year old boy who had been admitted to hospital three times during the preceding year. The patient lapsed into a critical condition with profound hypochloremia and hypokalemic metabolic alkalosis induced by extremely massive vomiting. The attacks of vomiting were spasmodic and self-limited. During the episodes of vomiting he fulfilled the criteria of pseudo-Bartter's syndrome, including hyperreninemia, hyperaldosteronism and normal blood pressure, but in the intervals between attacks he was completely asymptomatic. At the third admission, examination supported an overall clinical picture of bowel obstruction, which was confirmed by radiographic examination. Laparotomy revealed a midgut volvulus with intestinal malrotation. After surgery he made a good recovery and was symptom-free. In this patient, the high degree of hypochloremia and hypovolemia activated the renin-angiotensin-aldosterone system, then aldosterone promoted intensive reabsorption of sodium and excretion of potassium into the urine. Consequently the diagnosis of pseudo-Bartter's syndrome was establish on the basis of an extreme decrease in urinary chloride and an increase in urinary potassium concentration. It is relatively rare for vomiting due to intestinal malrotation to induce pseudo-Bartter's syndrome. The importance of considering this rare diagnosis in such cases is discussed.

Synergistic combinations and peptides in the inhibition of human immunodeficiency virus.

Various combinations of inhibitors of HIV reverse transcriptase were tested for inhibition of HIV replication in order to reveal any potential synergism or antagonism. PFA, a pyrophosphate analogue, gave synergistic inhibition of HIV replication in combination with both of the thymidine analogues AZT and FLT. The combination of PFA and AZT-TP gave only additive or weakly synergistic inhibition in a reverse transcriptase enzyme assay. The combination of AZT and FLT also gave synergistic inhibition of HIV replication, whilst the combination of AZT-TP and FLT-TP gave only additive or weakly synergistic inhibition of reverse transcriptase. Thus, the synergy does not arise from effects on reverse transcriptase alone but must be owing to other, cellular factors, such as effects on nucleoside metabolism or metabolism of the analogues. The results are consistent with the hypothesis that AZT may have an alternative mechanism of inhibition other than inhibition of reverse transcriptase. The diminished cytotoxicity observed in addition to the synergistic inhibition makes these combinations attractive from the point of view of combination chemotherapy. The inhibition of HIV replication by peptides from various parts of the V3 region of gp120 whose sequences were homologous with the tryptase inhibitor trypstatin was tested. Inhibitory activity was displayed by two peptides containing cysteine in their sequence. Antibodies to two peptides containing the two conserved cysteine residues from opposite sides of the neutralizing loop of gp120 were previously associated with protection from vertical transmission of HIV. The V3 region thus seems to be important for the function of gp120 and the transmission of HIV.

Structure-activity relationships of fluorinated nucleoside analogs and their synergistic effect in combination with phosphonoformate against human immunodeficiency virus type 1.

One hundred nucleoside analogs with fluorine substitutions at various positions on the pentose ring were evaluated for inhibitory activity against human immunodeficiency virus type 1 (HIV-1). Nine compounds emerged as inhibitors of HIV-1 replication, with various degrees of selectivity; the most active of these was 3'-fluoro-3'-deoxythymidine, followed by 5'-amino-3'-fluoro-3'-deoxyadenosine. Substitution of fluorine at the 2'-deoxy or 3'-deoxy position resulted in increased antiviral activity of the thymidine analogs, whereas the activity of adenosine or cytidine analogs was not increased by fluorination at either position. The most potent inhibitor, 3'-fluoro-3'-deoxythymidine, was shown to give synergistic inhibition of HIV-1 replication in combination with the PPi analog phosphonoformate.

Prediction of the distribution volumes of cefazolin and tobramycin in obese children based on physiological pharmacokinetic concepts.

So as to estimate the appropriate dose of antibacterial drugs in obese children, prediction of the volume of distribution in these children was attempted based on physiological pharmacokinetic concepts which had been constructed from results in normal-weight children. Serum concentration-time data after intravenous drip infusions of tobramycin and cefazolin were analyzed using noncompartmental analysis of obese children in whom the degree of obesity ranged from 30 to 80%. Volume of distribution at steady state (Vss) per total body weight of tobramycin was significantly less than that for normal-weight children (P less than 0.05), whereas the value of cefazolin was almost equal to that for normal-weight children. The equation to express the difference of Vss between cefazolin and tobramycin obtained in normal-weight children failed in obese children, suggesting that there is a large decrease in the extracellular space in obese children exceeding the interindividual variations in normal-weight children. The Vss value (liter) for tobramycin was predicted by using the equation 0.261 . (ideal body weight (kg) + 0.4 . [total body weight (kg) - ideal body weight (kg)]). The Vss value of cefazolin was predicted to be 0.3 . (predicted Vss of tobramycin) + 0.052 . total body weight (kg). A good correlation between the predicted and the observed Vss values was obtained.

Inhibition of human immunodeficiency virus in vitro by combinations of 3'-azido-3'-deoxythymidine and foscarnet.

We describe a synergistic effect of combinations of foscarnet and 3'-azido-3'-deoxythymidine against human immunodeficiency virus type 1 multiplication in cell culture, an additive effect of foscarnet and 3'-azido-3'-deoxythymidine triphosphate against human immunodeficiency virus type 1 reverse transcriptase, and a low toxicity in cell culture of combinations of the two drugs.

An analysis of the inhibition of replication of HIV and MuLV by some 3'-blocked pyrimidine analogs.

Some 3'-blocked pyrimidine analogs were synthesized and tested as inhibitors of replication of human immunodeficiency virus (HIV) and Moloney-murine leukemia virus (MuLV). The analogs were of 3 kinds: (1) analogs of 3'-azido-3'-deoxythymidine (AZT) in which the C-5 CH3 of the base was exchanged for H (AZU) or C2H5 (AZEU); (2) 3'-fluoro-3'-deoxythymidine (FLT) and analogs thereof, in which the C-5 CH3 of the base was exchanged for H (FLU), C2H5 (FLEU) or nC3H7 (FLPU); (3) the threo analogs of AZT (AZT increases) and AZU (AZU increases). All analogs were less active inhibitors of HIV replication than AZT, except FLT, which was as active as AZT. The 3'-fluoro analogs and AZEU did not inhibit MuLV replication at non-cytotoxic concentrations. Oral administration of FLT to MuLV-infected mice result in antiviral effects only at toxic drug levels. AZU and FLU were less potent inhibitors of HIV replication than AZT or FLT, but the 2'-deoxy uridine analogs were less cytotoxic to human embryonic fibroblasts than the thymidine analogs. The 5'-triphosphates of AZU, AZT, AZEU, FLT and FLEU were tested as inhibitors of the HIV- and MuLV-reverse transcriptases. Ranking of the Ki/Km values for HIV-RT resulted in the following order of potency of the 5'-triphosphates AZT = FLT greater than AZU greater than AZEU greater than FLEU. The 5'-triphosphates of AZEU, FLT and FLEU did not inhibit the MuLV-RT, which explains, in part, the lack of effect of these analogs against MuLV replication. The threo forms (azido "up") of AZU and AZT were less active inhibitors of HIV replication than the erythro forms (azido "down"). A 15N-NMR and 1H-NMR study showed that the furanose moieties of analogs with the azido function "up" assume a conformation distinct from that of the analogs with azido "down". This is due to intramolecular stabilisation of the "N" conformer in the threo ("up") diastereomer, due to interaction of the azido functions with the nucleobase and possibly the OH group of C-5' of the furanose. As discussed, this conformation might explain the decreased biological activity of threo forms compared with the erythro forms.

Interindividual changes in volume of distribution of cefazolin in newborn infants and its prediction based on physiological pharmacokinetic concepts.

The purpose of this study was to investigate factors affecting the volume of distribution of cefazolin (a beta-lactam antibiotic) in newborn infants with bacterial infections, and to propose a method for predicting the volume of distribution at steady state per body weight (Vdss/BW). Cefazolin and tobramycin (an aminoglycoside) were simultaneously given to newborn infants (aged 2 to 28 d), and plasma concentration-time data were analyzed on the basis of model-independent moment analysis. The Vdss/BW values ranged from 0.212 to 0.373 L/kg for cefazolin and from 0.384 to 0.541 L/kg for tobramycin. The unbound fraction of cefazolin in plasma (fp) fluctuated widely, from 0.22 to 0.83, among patients. The Vdss/BW value for cefazolin was characterized by both large extracellular water volume and a remarkable change in fp, and could be predicted as a function of fp using physiological pharmacokinetic concepts. Moreover, interindividual changes in the unconjugated bilirubin:albumin molar ratio were predominantly responsible for the individual variation in the fp values of cefazolin in newborn infants.

Nonsyndromatic paucity of intrahepatic bile ducts in congenital syphilis. A case report.

The first case of nonsyndromatic paucity of the intrahepatic bile ducts is reported in congenital syphilis. The patient, a 2-week-old female, was born at the 31st week of gestation, weighing 1,910 g. She had a high titer of IgM antibody to Treponema pallidum and sera from both parents also showed a positive reaction in the hemagglutination test for Treponema pallidum. The patient had hepatosplenomegaly and increasing jaundice, and died of respiratory failure on the 70th hospital day. Autopsy examination revealed paucity of the intrahepatic bile ducts, prominent giant cell transformation of hepatocytes, cholestasis and extramedullary hematopoiesis of the liver. The ratio of the number of intrahepatic bile ducts to that of the portal tracts was approximately 0.2:1. There was marked proliferation of atypical bile ductules at the margin of the portal tracts. The exact relation of this paucity to Treponema pallidum remains unknown.

Comparative distribution kinetics of cefazolin and tobramycin in children.

The time courses of drug concentration in serum after i.v. drip infusion of 2 mg/kg of tobramycin and 25 mg/kg of cefazolin in children were analyzed by model-independent moment analysis. The volume of distribution at the steady state per body weight (Vdss/BW) of tobramycin was in the range of 212 to 335 ml/kg and that of cefazolin was 119 to 156 ml/kg. A plot of the differences of Vdss/BW obtained in the same child for tobramycin and cefazolin against the value of Vdss/BW of tobramycin gave a linear regression line (r = 0.971). The magnitude of Vdss (1) of tobramycin could be well interpreted as corresponding to the extracellular water volume. In the case of cefazolin, the extracellular water space accounts for about 60% of the total distribution volume. The remaining 40% of the total Vdss of cefazolin was considered to be accounted for by the disposing organs.