The Predominant Contribution of Oligopeptide Transporter PepT1 to Intestinal Absorption of β-Lactam Antibiotics in the Rat Small Intestine

Although recent evidence suggests that certain β-lactam antibiotics are absorbed via a specific transport mechanism, its nature is unclear. To confirm whether peptide transport in the rat can be largely ascribed to the intestinal oligopeptide transporter PepT1, the transporter has been functionally characterized and its significance in the intestinal absorption of β-lactam antibiotics was evaluated. For evaluation of transport activity complementary RNA (cRNA) of rat PepT1 was synthesized in-vitro and expressed in Xenopus laevis oocytes. cRNA induced uptake of several β-lactam antibiotics and the dipeptide [¹⁴C]glycylsarcosine; this was specifically inhibited by various dipeptides and tripeptides but not by their constituent amino acids or by terra- or pentapeptides. The transport activity of PepT1 for β-lactam antibiotics correlated well with their in-vivo intestinal transport and absorption. Furthermore, mutual inhibitory effects on uptake were observed between glycylsarcosine and β-lactam antibiotics. Hybrid depletion of the functional expression of rat PepT1 in oocytes injected with rat intestinal epithelial total mRNA was studied using an antisense oligonucleotide corresponding to the 5′-coding region of PepT1. In oocytes injected with rat mRNA pre-hybridized with the antisense oligonucleotide against rat PepT1, the uptake of [¹⁴C]glycylsarcosine was almost completely abolished, whereas its uptake was not influenced by a sense oligonucleotide for the same region of PepT1. Similarly, the uptake of β-lactam antibiotics was also reduced by the antisense oligonucleotide against rat PepT1. These results demonstrate that the intestinal proton-coupled oligopeptide transporter PepT1 plays a predominant role in the carrier-mediated intestinal absorption of β-lactam antibiotics and native oligopeptides in the rat.     

Assessing the clinical utility of the magnetic stimulator for measuring response latencies in the laryngeal muscles

Our purpose was to assess the use of magnetic stimulation for measuring conduction time of the recurrent and superior laryngeal nerves in 10 normal volunteers (7 male, 3 female). Subjects underwent laryngeal electromyography and magnetic stimulation of the vagus nerve bilaterally at the mastoid tip with a figure 8 coil. Mean muscle response latencies were measured and examined for consistent differences. Thyroarytenoid muscle response latencies were consistently longer than those in the cricothyroid muscle. Left thyroarytenoid muscle latencies were consistently longer than those on the right in agreement with bilateral asymmetry of these nerves. No appreciable differences were observed in cricothyroid muscle latencies when the right side was compared with the left. Results were consistent and reproducible within a broad range, but appreciable intersubject variability was observed. The limited sample size was unable to support a correlation with anthropometric variables, although an association was indicated. Magnetic stimulation with this technique has great potential for use in neurolaryngologic studies. (Otolaryngol Head Neck Surg 1996;114:761-7.)     

A multicenter,randomized, controlled trial of intravenous gamma globulin therapy in children with acute Kawasaki disease

We studied the effect of intravenous, polyethyleneglycol-treated, human immunoglobulin, administered at 200 mg/kg per day (group A: n = 147; male 86, female 61; age < 1 year, 50) or 400 mg/kg per day (group B: n = 152; male 87, female 65; age < l year, 52) for five consecutive days and compared it with freeze-dried, sulfonated human immunoglobulin [group C: n = 152; male 87, female 65; age < 1 year, 51), administered at 200 mg/kg per day for five consecutive days, on the prevention of coronary artery abnormalities in Kawasaki disease. Echocardiograms were interpreted blindly and independently. Proportions of 87.1%, 95.4%, and 82.3% in groups A, B, and C, respectively, had no coronary artery abnormalities. The confidence limits of difference between the proportions of groups A and C, groups B and C, and groups B and A were −4.4% and 10.4%, 7.8% and 15.9%, and 4.0% and 10.8%, respectively. Duration of fever and serum immunoglobulin G (IgG) levels were correlated with the prevalence of coronary artery abnormalities. We concluded that intravenous, polyethyleneglycol-treated, human immunoglobulin and freeze-dried, sulfonated human immunoglobulin had clinically equivalent effects on coronary artery abnormalities, and that five daily doses of 400 mg/kg of intravenous, polyethyleneglycol-treated, human immunoglobulin is more effective than that of 200 mg/kg gamma globulin.     

Correlation between Dose and Tumor Response in the Radiotherapy of Lung Cancer of Various Histological Types

Correlation between dose and tumor response by cell types wasdetermined in 50 patients with lung cancer in order to predictthe possibility of further tumor regression. The TDF (time-dose-fractionation)concept was used as dose factor. The radiation source was a cobalt-60 -ray or linear accelerator10 MV X-ray. As a routine regime a fraction dose of 2 Gy fivetimes per week was given to 39 of the 50 patients, but a doseof 2 Gy three times per week or of 1.5 Gy five times per weekwas given to seven and four patients, respectively. Radiation response was the best in small cell carcinoma andbetter in adenocarcinoma than in squamous cell carcinoma, showinga tumor regression rate of 50% or more in 90%, 80% and 58% ofthe patients, respectively. The correlation between tumor regression rate and TDF valueswas good in squamous cell carcinoma (r=0.73) and small cellcarcinoma (r=- 0.72), but poor in adenocarcinoma (r=- 0.10).These results suggest that in squamous cell carcinoma improvementof tumor regression can be expected by increasing TDF values,and in adenocarcinoma and small cell carcinoma the optimal TDFvalues are about J00 and 60 to 80, respectively.     

Treatment of Osmidrosis with the Cavitron Ultrasonic Surgical Aspirator

BACKGROUND: Axillary osmidrosis is an uncomfortable condition that can be a personal or social handicap. OBJECTIVE: The objective was to present the treatment of osmidrosis with the Cavitron ultrasonic surgical aspirator (CUSA). MATERIALS AND METHODS: Fifteen patients (3 males and 12 females) underwent surgery for bilateral axillary osmidrosis with the CUSA. RESULTS: The outcome of this operation with the CUSA was evaluated by the patients themselves according to the following criteria. Postoperative improvement was evaluated as good when the odor was decreased by >75%, fair when it was decreased by > or =50 and < or =75%, and poor when it was decreased by <50%. A total of 15 patients (3 males and 12 females) were evaluated. Eight patients (53.3%) had a good result, 6 patients (40%) had a fairly good result, and 1 patient (6.7%) had a poor result. None of the patients experienced any complications, such as skin necrosis, infection, or serous cyst. One dissatisfied patient underwent reoperation and achieved a good result after the second procedure. CONCLUSIONS: This treatment of osmidrosis with the CUSA achieves satisfactory therapeutic efficacy.     

Renal Excretion of Vancomycin in Rats with Acute Renal Failure

We have investigated the renal excretion of vancomycin in rats with acute renal failure (ARF) induced by uranyl nitrate or cisplatin. The renal clearance of the antibiotic after uranyl nitrate or cisplatin injection was separately evaluated by calculating the glomerular filtration rate (GFR) and secretory clearance. The reduced renal clearance of vancomycin in these ARF rats was a result of a decrease in both GFR and secretory clearance. The extents of the decreases in GFR and in secretory clearance were not, however, proportional, the extent of the decrease in secretory clearance being more pronounced. These results suggest that the renal tubular secretion of vancomycin was reduced more predominantly than glomerular filtration in these ARF models.     

Studies on the immunogenicity of a recombinant ookinete surface antigen Pbs21 from Plasmodium berghei expressed in Escherichia coli

Plasmodium berghei ookinete surface antigen (Pbs21), was produced as a fusion product with maltose binding protein (MBP) in Escherichia coli and used to induce transmission-blocking immunity in mice. Specificity of induced antibody was confirmed by Western blotting with native ookinete Pbs21, and by the indirect immunofluorescent antibody test on ookinete bloodfilms. Immunized mice were infected with P. berghei and transmission to Anopheles stephensi mosquitoes determined by both the intensity and prevalence of oocyst infections. Compared with a control group immunized with MBP alone the maximum blockade of oocyst intensity was 66% in the mice immunized with recombinant MBP-Pbs21. Over nine experiments blockade averaged only 33%. By comparison with native Pbs21 protein, which usually induces 90% blockade, our data suggests the recombinant protein produced in this bacterial system is a less effective immunogen despite expressing epitopes recognized by known transmission-blocking monoclonal antibodies.     

A proposal of subcategorization of bacterial prostatitis: NIH category I and II diseases can be further subcategorized on analysis by therapeutic and immunological procedures

Aim: We propose preliminarily that acute (category I of the NIH consensus definition) and chronic prostatitis (category II) can be subcategorized into primary and recurrent diseases based on the precise analysis of the clinical course and the immunological parameters in prostatic secretions of our cases. Methods: Five patients with stone‐free, acute febrile prostatitis and nine patients with acute episodes of afebrile urinary infection were included. The expressed prostatic secretions (EPS) were collected soon after the acute illnesses subsided after medication administration and they were examined microscopically, bacteriologically, and serologically. First‐line medications were cefem antibiotics with conventional doses for febrile cases and low doses for afebrile cases. They were administered for at least 2 weeks. Second‐line conventional medication with sulfamethoxazole‐trimethoprim or levofloxacin was given only to the patients in whom remaining prostatic infections were revealed. Results: The first‐line medications were successful in all patients and they promptly became asymptomatic in 1 week. All the EPS were infected except for two afebrile cases. Prostatic infections were eradicated by second‐line conventional medications. In a patient with afebrile prostatitis whose EPS were free of macrophages and immunoglobulin (Ig)M, the eradication of prostatic pathogens was achieved without second‐line antibacterial medication. Conclusions: Bacterial prostatitis could be classified into primary and recurrent chronic infections in each of the febrile (category I) and afebrile (category II) illnesses. A cefem regimen in varying doses was a clue for differential diagnosis as it did not affect the pathogens in the prostatic ducts or acini unless heavy urine reflux occurred in the ductal draining systems. Macrophages and immunoglobulins, especially IgM, in the EPS were useful immunological parameters to differentiate primary and recurrent infections of the prostate. Fluoroquinolones or sulfamethoxazole‐trimethoprim should not be employed in acute urinary infections in male patients until the confirmation of prostatic infection to avoid injudicious use of them, which might cause an increasing prevalence of resistant uropathogens in the community. The evacuation of the prostate by repetitive massage seemed to be effective to enhance the prompt eradication of pathogens from the prostatic tissue and to keep patients asymptomatic throughout the course of the disease by preventing tissue pressure elevation.     

Clinical characteristics and proliferating activity of intrahepatic cholangiocarcinoma

Abstract To assist in the development of new approach to the palliation and treatment of intrahepatic cholangiocarcinomas, we classified tumours into mass-forming (MF), peri-ductal extension (PD), and spicula-forming (SF) types in 14 subjects who underwent surgical treatment. Lymph node metastasis and microscopic lymphatic invasion were pronounced in the PD and SF types. Furthermore, in SF type tumours the incidence of microscopic vascular and perineural invasion was high. The proliferating cell nuclear antigen labelling index, a reflection of the proliferation rate of tumour cells, was significantly higher in PD and SF types than in the MF type. The prognosis associated with the MF type tended to be better than that of the other two types.
For the MF type, liver resection with tumour free margins must be performed, whereas for the PD and SF types, aggressive treatment, that is a combination of extensive liver resection, lymph node dissection, and effective adjuvant anti-cancer therapy should be provided to aim at life-long cure.