[Dynamic analysis of airway temperature in dogs breathing cold air].

Exercise in cold, dry air induces bronchoconstriction. However, the time course of airway cooling during the breathing of cold air has not been investigated. In this study in dogs, the temperatures of tracheal gas and the tracheal wall were measured continuously while the animal was breathing cold air at approximately 4.5 degrees C. The temperature of the tracheal gas decreased during the inspiratory phase, increase slightly early in the expiratory phase, and then decreased to the level at end-expiration. The lowest temperature of the tracheal gas decreased significantly, from 29.7 +/- 2.4 degrees C (mean +/- SD) to 25.7 +/- 2.8 degrees C. The highest temperature also changed significantly, but the decrease was less than 1 degree C. The lowest temperature of the tracheal wall decreased from 31.1 +/- 2.6 degrees C to 30.5 +/- 2.5 degrees C during cold-air breathing, but the difference was not significant. When a dog inspired deeply during a cough, the temperature of tracheal gas did not decrease linearly with the progression of inspiration. However, the decrease in the tracheal wall temperature was almost directly proportional to inspiratory volume. We concluded that both the tracheal gas and the tracheal wall temperatures were resistant to cooling with cold-air breathing. It remains uncertain whether rapid, deep breathing during exercise decreased the tracheal wall temperature.

Effects of "isolating hemodialysis" on prevention of methicillin-resistant Staphylococcus aureus cross-infection in a hemodialysis unit.

AIM: To evaluate the effects of a contact isolation program against methicillin-resistant Staphylococcus aureus (MRSA) cross-infection among patients in a hemodialysis unit. CLINICAL SETTING AND METHODS: In all patients maintaining hemodialysis therapy were tested for MRSA infection and who had MRSA infection, not only inpatients but also outpatients were separated into a designated area (isolating hemodialysis). Clinically isolated MRSA strains were clonotyped with coagulase typing, staphylococcal enterotoxin typing and restriction enzyme analysis of plasmid DNA. RESULTS: The frequency of patients with MRSA infection was 4.5% before starting this protocol and was reduced to 2.9% two and a half years later. At this time, MRSA was isolated from the 8 patients. These 8 clinical strains were differentiated into 6 clonotypes and 3 strains showed the same patterns. Two of 3 were isolated from inpatients and the other was from a patient with community onset MRSA colitis. In this case, most MRSA infections were independent under prophylaxis control and cross-infection was observed only once between hospitalized patients who stayed in a same ward. CONCLUSION: This "isolating hemodialysis" should be useful to prevent cross-infection among patients in end-stage renal disease in a dialysis unit.

Respiratory-related bronchial rhythmic constrictions in the dog with extracorporeal circulation.

Respiratory-related bronchial rhythmic contraction was quantitatively analyzed in eight paralyzed dogs. The caliber of the fifth-generation bronchus was continuously measured as the pressure (Pbr) of a balloon-tipped catheter under the condition of complete immobilization due to extracorporeal oxygenation. Pbr changed rhythmically in synchrony with phrenic nerve activity (PNA) bursts. Rhythmic bronchial constriction started at 1.4 +/- 0.49 (SD) s after onset of PNA, reached a maximum level at 2.8 +/- 1.6 s after termination of PNA, and then decreased exponentially with a time constant of 6.9 +/- 2.5 s. When the respiratory rate of dogs increased at hypercapnia, the various bronchial contractions fused to behave like a tonic contraction. The rhythmic component of this contraction was separated and quantitatively analyzed. Each rhythmic Pbr amplitude linearly increased with increases in PNA amplitude, whereas the end-expiratory Pbr level was not significantly changed. Bilateral efferent nerve transection did not decrease the end-expiratory Pbr level. In response to electric stimulation of efferent nerve fibers, the bronchus did not maintain tonic contraction. We concluded that vagally mediated commands contract bronchial smooth muscle only intermittently and that most of bronchial resting tension may thus be attributed to the summation of rhythmic contractions.

Role of cholinergic neural transmission on airway resistance in the dog.

The unique contractile profiles of bronchial smooth muscle (Kondo et al., 1995) and its neural control were investigated by comparing responses of the bronchus and trachea to acute hypercapnia, stimulation of vagus efferent fibers before and after intravenous atropine, and intravenous acetylcholine in decerebrated and paralyzed dogs. During acute hypercapnia, airway resistance represented by peak airway pressure (Pedley et al., 1970) significantly increased as well as tracheal tension (Ttr). During electric stimulation of the vagal efferent fibers, Ttr increased and was sustained throughout the simulation period while the peak airway pressure was not maintained at the peak level. The peak Ttr and the airway resistance (Raw) calculated from ventilatory flow and airway pressure increased with increases in intensity of electric stimulation. Ttr reached its maximal level at an intensity 16 times of the threshold (T), while Raw became maximal at 4T. Although both the Ttr-stimulus intensity and Raw-intensity curves were shifted to the right by administration of intravenous atropine, the Raw curve shifted more to the right than the Ttr curve with the same dose of atropine. When muscular muscarinic receptors were directly stimulated by intravenous acetylcholine, Ttr once increased and then decreased promptly while peak airway pressure remained at a high level for a few minutes. These findings suggested that the bronchus is more sensitive to vagal efferent stimulation and susceptible to competitive antagonist of actylcholine than the trachea. In conclusion, the contractile profiles of the fifth-order bronchus we have reported (Kondo et al., 1995) were reflected in airway resistance, and the neuromuscular junction may be the site of adaptation of bronchoconstrictor response to motor nerve adaptation.

[Physiological role of respiratory-related bronchial constriction].

The respiration-related rhythmic constriction of the fifth-generation bronchi was analyzed in 11 tracheostomized dogs. During spontaneous breathing, the bronchial pressure (Pbr) estimated with a balloon-tipped catheter increased almost in parallel with the pleural pressure (Ppl) in the early inspiratory phase, but decreased in the late inspiratory phase. The parallel duration/inspiratory duration was 0.72 +/- 0.19 (mean +/- SD). This finding was more prominent in hypercapnia, but statistical significance was not obtained. When the efferent phrenic nerve fibers were electrically stimulated (pulse train, 0.1 ms, 30 Hz, 5 V, 2 s), Pbr changed almost in parallel with Ppl during the inspiratory phase, and expiration was completed significantly earlier than during spontaneous breathing (time constant 0.17 +/- 0.06 s vs 0.26 +/- 0.07 s). Bronchial constriction in early expiration may increase airway pressure and keep patency of the peripheral bronchi.

[A case of interstitial nephritis induced by a super antigen produced by methicillin-resistant Staphylococcus aureus (MRSA) presenting as acute renal failure].

We report the case of a 21-year-old man who had been developing acute renal failure with Methicillin-resistant Staphylococcus aureus (MRSA) colitis and sepsis. He was admitted for consciousness disturbance, nausea, vomiting, and diarrhea. Oliguria was also observed and his serum creatinine level was elevated to 10 mg/dl. Urinary protein was positive and an abundance of hyaline cast were seen in urinary sedimentation. Diarrhea and pyrexia were prolonged and serum C-reactive proteins were elevated, but lymphocyte and leukocyte counts temporarily decreased from the 3rd to the 6th hospital day and remained low until normalizing after the 14th day. His clinical symptoms improved with hemodialysis (HD) and effective antibiotic therapies. An MRSA strain producing toxic shock syndrome toxin-1 (TSST-1), a super antigen which specifically stimulates human V beta 2-positive T cells, was separated from his feces and blood. To ascertain the cause of his renal dysfunction, a renal biopsy was performed on the 8th day. His renal histology revealed acute interstitial nephritis with severe inflammatory cell infiltration around the medullary areas without glomerular changes. Most of the infiltrated cells were small monocytes, and lymphoid cells were rich in the interstitium. With immunohistochemical staining, over 70% of T-cells were V beta 2-positive. TSST-1-producing MRSA was detected in his blood specimen. Furthermore, V beta 2-positive T cells were accumulated in the renal intersititium, and transient lymphocytopenia was observed. These data suggested the following possible pathogenesis for interstitial nephritis: TSST-1 acts as a super antigen in the renal interstitium where major histocompatibility complex (MHC) is class-2-positive, thereby resulting in interstitial nephritis with T cell migration.

An increase in the threshold of citric acid-induced cough during chest wall vibration in healthy humans.

This study tested the hypothesis that the afferent input from the respiratory muscles may be involved in the neural mechanisms inducing cough responses. Coughing was evoked in conscious healthy humans by the inhalation of citric acid aerosol of several concentrations either during or not during chest wall vibration (100 Hz) at the right second intercostal space or during vibration of the right thigh. The mean threshold citric acid concentration to induce coughing was significantly higher during chest wall vibration (geometric mean, 131.8 mg/ml) than without vibration (75.9 mg/ml). Vibration after topical anesthesia of the chest wall skin did not significantly change the threshold concentration of citric acid. The threshold citric acid concentration during vibration of the right thigh did not significantly differ from that without vibration. We concluded that inputs from the chest wall afferent, presumably from the intercostal muscle or costovertebral joint, may have an inhibitory effect on the initiation of coughing at the higher neural structure in conscious humans.

Insertion/deletion polymorphism in intron 16 of the ACE gene and left ventricular hypertrophy in patients with end-stage renal disease.

We studied the relationship between polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene and left ventricular (LV) hypertrophy in uremic patients treated with hemodialysis therapy. The LV parameters were not different for age-, hematocrit-, and blood pressure-matched patients in DD, ID, and II genotype groups. The most important factor for LV hypertrophy was systolic blood pressure, which correlated with the posterior wall thickness (r=0.35; P=0.001) and LV mass index (LVMI; r=0.23; P=0.032). Among nonhypertensive patients, the frequency of interventricular septum (IVS) hypertrophy (>12 mm) and hypertrophy in LVMI (>145 g/m2) was significantly greater in patients with the DD genotype than in I allele-positive (+) patients. The odds rate for IVS hypertrophy was 5.04 (95% confidence interval, 1.15 to 24.8). These data suggest that the DD genotype of the ACE gene polymorphism is a contributory factor for the development of LV hypertrophy in patients with end-stage renal disease (ESRD).

Contribution of brainstem hypoperfusion to the tracheal and phrenic nerve responses to high-pressure lung inflation in the dog.

Lung inflation to high airway pressure is known to produce tracheal constriction following an initial dilation. This is attributed to stimulation of various pulmonary receptors. In an attempt to find cause of this response, we investigated in 20 decerebrated, tracheostomized and paralyzed dogs changes in the tracheal smooth muscle tension, arterial pressure and the phrenic nerve activity to high-pressure lung inflation. A high-pressure lung inflation evoked a contraction of tracheal smooth muscle following its short-lasting relaxation, and a persistent hypotension. After hilar denervation which eliminated all pulmonary afferents, a high-pressure lung inflation still evoked contraction of tracheal smooth muscle (an increase of 3.7 times) and augmented amplitude and frequency of phrenic bursts. Bilateral transections of sympathetic fibers to the lung, or blockade of arterial perfusion to the carotid sinus and denervation of the carotid sinus bilaterally did not alter the tracheal muscle and phrenic responses to a high-pressure lung inflation. We further found that severe hypotension alone caused similar responses of the tracheal smooth muscle contraction and augmented phrenic activity. Finally, when blood supply to the brainstem was transiently obstructed by clamping both the vertebral and internal carotid arteries bilaterally, the same responses were observed. In contrast, when blood hypoperfusion to the brainstem was prevented by means of extracorporeal circulation, a high-pressure lung inflation failed to evoke such contraction of tracheal smooth muscle and or increased phrenic activity. After transection of the vagus nerves bilaterally at the cervical level the tracheal muscle response to lung inflation was abolished but that of phrenic nerve was preserved. We concluded that the tracheal smooth muscle contraction and phrenic responses induced by high-pressure lung inflation may be in part attributed to brainstem hypoperfusion.

Contribution of airway resistance to airway pressure during mechanical ventilation: an experimental study.

Although airway resistance (R) is an important parameter of the pulmonary condition, its determination during mechanical ventilation is not easy. Most physicians estimate R from peak airway pressure during mechanical ventilation. We assessed the relationship between R and peak airway pressure by a computer simulation. The time course of airway pressure (Ptr) during mechanical ventilation was calculated from the airway pressure at end-inspiration and respiratory flow, allowing for the buffering effect of the dead space. The parameters for computer simulation were obtained from 5 paralyzed and mechanically ventilated dogs. The predicted Ptr curve was a function of airway resistance. Since R was not directly determined by the animal experiments, we determined R by using the Ptr curve most closely approximating the original Ptr curve as the true R. The R-peak tracheal pressure relationship predicted by computer simulation showed that the peak airway pressure increased almost linearly with increases in R. However, in computer simulation, when R was increased 10-fold from the value at airway relaxation, the peak airway pressure increased only 6-fold from the corresponding value. We conclude that peak airway pressure is a relatively insensitive parameter for the estimation of airway constriction during mechanical ventilation.

T-cell activation modified by parathyroid hormone (PTH) in patients with end-stage renal disease.

We studied the effect of parathyroid hormone (PTH) on the proliferation of T cells from patients with end-stage renal disease (ESRD) (n = 16) and normal subjects (n = 20). In patients with ESRD, T-cell proliferation expressed as stimulation index (SI) was significantly decreased from 99.2 +/- 31.2 to 46.3 +/- 10.8, when 10 ng/ml of recombinant PTH (rPTH) was added in vitro. The reduction of SI with rPTH was dose dependent. However, in normal subjects, the SI was increased from 56.2 +/- 13.6 to 67.9 +/- 16.5 (p < 0.01) by addition of rPTH. These findings were also shown by allo or specific antigen-induced T-cell stimulation. When T cells from normal subjects were pretreated with 10 ng/ml of PTH, with 100 mg/dl of urea or with a condition of pH 7.0, the effect of rPTH was changed to decrease the T-cell proliferation induced by anti-CD3 antibody. These data suggested that uremic state, including hyperparathyroidism, changed the response of T cells against PTH.

Improvement in rheumatoid arthritis following application of an extracorporeal granulotrap column, G-1.

Patients with rheumatoid arthritis (RA) showed significantly (P < 0.01) increased numbers of granulocytes in their peripheral blood compared with normal donors and patients with osteoarthritis, and this finding correlated with interleukin-6 and C-reactive protein levels and active joint score. Then, 17 patients with RA were treated eight times in 4 weeks with a newly developed extracorporeal granulotrap column containing cellulose acetate beads (G-1 column). This column reduced granulocytes in the outflow blood by 50.2% compared with inflow counts. To evaluate the efficacy of G-1 therapy, 17 patients were followed for 12 weeks from the beginning of this therapy. The modified Lansbury index (LI) for monitoring RA activity significantly improved from a pretreatment mean score of 60.8% to a posttreatment score of 51.3%. The lowered scores were maintained up to 12 weeks after the initiation of therapy. Of the four LI items, tender and swollen joint scores showed the most significant improvement, with the tender joint score showing a particularly significant decrease throughout the study period. No serious side-effects were observed. These findings suggested that G-1 therapy was effective for RA.

Efficacy of gentian violet in the eradication of methicillin-resistant Staphylococcus aureus from skin lesions.

The efficacy of gentian violet (Gv) in eradicating methicillin-resistant Staphylococcus aureus (MRSA) in decubitus ulcers was investigated. Decubitus ulcers (a total of 18 cases) were scrubbed with Gv aqueous solution 0.1% and ointment containing Gv 0.1% was applied daily. MRSA was not detected in these lesions for 3-34 days (average, 10.5 +/- 2.5 days) after the application of Gv ointment. Before this trial, all patients were treated with povidone-iodine and antibiotics; however, those treatments were not effective in eradicating MRSA from skin lesions. Skin irritation and other systemic side effects caused by Gv were not observed. Our data suggest that Gv is a useful agent for treatment of the decubitus ulcers infected with MRSA.

Osmolality-induced changes in aldosterone secretion involve a chloride-dependent process.

Alterations in extracellular osmolality have a powerful inverse effect on aldosterone secretion that is associated with sustained changes in cell volume. With dispersed bovine glomerulosa cells grown in primary culture, the effects of alterations in osmolality on cell volume measured by the distribution of [14C]urea and [3H]mannitol were determined in the presence and absence of chloride. In the presence of chloride, decreases in osmolality increased cell volume, whereas angiotensin II (< 4 x 10(-9) M) did not affect cell volume. When chloride was removed from the medium (replacing chloride with the impermeant methyl sulfate ion), cell volume decreased significantly, but basal aldosterone secretion was not altered. In the absence of chloride, the increases in cell volume, cytosolic calcium concentration, and aldosterone secretion induced by decreases in osmolality were significantly suppressed. The replacement of chloride with the methyl sulfate ion suppressed the increases in both cytosolic calcium concentration and aldosterone secretion induced by low (< 4 x 10(-9) M) but not high (4 x 10(-8) M) concentrations of angiotensin II. The results suggest that reductions in osmolality increase cell volume, partly by inducing an influx of chloride ions that contributes to the total net influx of water. Reductions in cell volume caused by an increase in osmolality or by replacing the chloride ion with the impermeant methyl sulfate ion may induce alterations in membrane stretch that may decrease the angiotensin II-induced increase in cytosolic calcium concentrations, which in turn suppresses aldosterone secretion.

[Effect of gentian violet on the elimination of methicillin-resistant Staphylococcus aureus (MRSA) existing in the decubitus region].

Methicillin-resistant Staphylococcus aureus (MRSA) is frequently isolated from skin lesions, such as in the decubitus region. There is a possibility that MRSA through these lesions can spread widely in a hospital. However, local treatment with most antibiotics and antiseptics (povidone-iodine) is not effective to eradicate MRSA from the infected decubitus. We have recently demonstrated that gentian violet (Gv) possessed a bactericidal effect against MRSA isolated from clinical specimens in vitro. This examination evaluated whether or not a topical ointment containing 0.1% Gv is effective to eradicate MRSA which existed in decubitus regions. Decubitus (14 clinical cases, ages 59-87 years) infected with MRSA were treated with 0.1% Gv-ointment once or twice daily after bathing in 0.1% Gv aqueous solution. Although all patients were treated with povidone-iodine and 9 out of 14 patients were given either local or systemic administration of antibiotics, those treatments were not effective to eradicate MRSA from decubituses. However, MRSA was not detectable in all cases within 34 days (average: 10.8 days +/- 2.7) after treatment with 0.1% Gv-ointment. The eradication of MRSA from decubitus areas tended to be delayed, depending upon the size and depth of decubituses (Grade III and IV) and complications such as diabetes mellitus. Skin irritability was not observed in any patients. These results suggest that 0.1% Gv-ointment is a useful material for the treatment of the MRSA-local wound infection. Treatment with Gv-ointment to MRSA-infected decubitus may exhibit a protective effect with regard to infection with MRSA in hospital.

[A case of mesangioproliferative glomerulonephritis (GN) associated with unique lesions of juxtaglomerular apparatus (JGA) and interstitium].

A case of mesangioproliferative glomerulonephritis (GN) associated with unique lesions of the juxtaglomerular apparatus (JGA) and interstitium is discussed. A 31-year-old Japanese woman who developed eyelid and pretibial edema with nephrotic-range proteinuria (4.8 g/day) and without hematuria, was admitted. Her proteinuria and edema quickly disappeared within 7 days after admission without treatment. Her blood examinations revealed hypocomplementemia on admission, but complement recovered to normal levels after 4 weeks. A renal biopsy specimen obtained on the 5th day of admission revealed moderate mesangioproliferative GN with marked periarteriolar inflammatory cell infiltrations in the JGA and occasionally in the tubular interstitium. Depositions of IgG, IgA, IgM and C3 were observed in the glomerular mesangial regions and some capillary walls, but not in the extraglomerular areas. Titers of GN-related viral antigens were not increased. Although the renal histology of this case was similar to that of experimental acute cytomegalovirus (CMV) GN in mice (described by Smith, R.D.), we could not detect CMV antigen by indirect immunofluorescent method or the virus-like particles by electron microscopy. Clinical cases of nephropathy combining lesions of the glomerulus, JGA, and interstitium are very rare. We herein report a patient with mesangioproliferative GN, who underwent an acute clinical course associated with unique inflammatory lesions of the JGA and/or interstitium.

Osmolality and potassium cause alterations in the volume of glomerulosa cells.

Alterations in extracellular osmolality have a powerful inverse effect on aldosterone secretion and potassium- and angiotensin-stimulated aldosterone secretion. Whether alterations in extracellular osmolality produced sustained changes in cell volume that may contribute to the regulation of aldosterone secretion is not known. Using dispersed bovine glomerulosa cells grown in primary culture, the effect of alterations in osmolality on cell volume, measured by the distribution of [14C]urea and [3H]inulin and videometric analysis of the surface area of glomerulosa cells, was determined. Alterations in osmolality had an inverse effect on cell volume and surface area. Changes in cell volume induced by exposure to anisotonic medium were 52% greater (P > 0.02) than that predicted by the changes in osmolality. Increases in potassium concentration also caused sustained (1-h) concentration-dependent increases in cell volume and surface area. Angiotensin-II did not increase glomerulosa cell volume, but did produce a small dose-dependent transient increase in cell surface area. The results demonstrate that alterations in osmolality do cause sustained changes in cell volume, and thus, membrane stretch could be an important part of the cellular mechanism responsible for causing osmolality-induced changes in the cytosolic calcium concentration and subsequent alterations in aldosterone secretion. Alterations in membrane stretch may also be an important component of potassium-induced, but not angiotensin II-induced, aldosterone secretion.

[The oral 1-25 dihydroxyvitamin D3 pulse therapy in hemodialysis patients for the early treatment of secondary hyperparathyroidism].

It is said that maintenance hemodialysis patients are already suffering from secondary hyperparathyroidism (2HPT) from early stage of chronic renal failure. The treatment of 2HPT in this stage is very important for preventing renal osteodystrophy (ROD). But many long-term dialysis patients are still afflicted with ROD although vitamin D have been used for treatment. In this study, an oral administration of 1-25 (OH)2 D3 (4 micrograms) with pulse therapy twice a week at the day before hemodialysis was started for 12 weeks. The concentration of 1-25 (OH)2D3, total calcium (Ca), ionized calcium (Ca++), alkaline phosphatase (ALP) and parathyroid hormone (PHT) in serum were measured not only before and after every 2 hours of administration a day, but also for 12 weeks after that. The peak of serum 1-25 (OH)2D3 could be sufficiently elevated after 8 hours, and the slight peak of Ca++ could be seen after 8 hours as well. But the level of total calcium could not increased. Although the level of only HS-PTH has not increased after 24 hours, a significant reduction in serum level of C-PTH, intact-PTH and HS-PTH could be recognized after 12 weeks finally. This pulse therapy was effective in reducing the serum level of PTH in this early stage from beginning hemodialysis. But, it needs further studies for the standard treatment.