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Biomedical subjects

K Hsu

Publications and source records attributed to K Hsu.

At least 55 records · Page 3Linked to original sources

Clinical efficacy of spinal instrumentation in lumbar degenerative disc disease.

In review of 871 lumbar fusion procedures performed during the last 8 years, the theoretical advantages of lumbar spinal instrumentation are not borne out in simple discogenic disease. Four groups of 30-35 patients without previous surgery who underwent fusion by different techniques were matched for age, sex, length of follow-up, surgeons, number of levels fused, duration of preoperative symptoms, diagnosis, and type of third party payer. At least for the diagnoses of herniated disc with segmental instability and the instrumentation systems used in this study, results were superior with no internal fixation. This is in keeping with the higher complication rates and frequent need for implant removal reported by many authors.

Adult↗

The RNA polymerase III terminator used by a B1-Alu element can modulate 3' processing of the intermediate RNA product.

The dispersion of short interspersed elements (SINEs) probably occurred through an RNA intermediate. B1 is a murine homolog of the human SINE Alu; these elements are composed of 5' G + C-rich regions juxtaposed to A-rich tracts and are flanked by direct repeats. Internal promoters direct RNA polymerase III to transcribe B1 and Alu elements and proceed into the 3' flanking DNA until it reaches a (dT)4 termination signal. The resulting transcripts contain 3'-terminal oligo(U) tracts which can presumably base pair with the A-rich tract to form self-primed templates for reverse transcriptase and retrotransposition. Nuclear extracts from mouse tissue culture cells contain an RNA processing activity that removes the A-rich and 3'-terminal regions from purified B1 RNAs (R. Maraia, Nucleic Acids Res. 19:5695-5702, 1991). In this study, we examined transcription and RNA processing in these nuclear extracts. In contrast to results with use of purified RNA, nascent transcripts synthesized in nuclear extract by RNA polymerase III are not processed, suggesting that the transposition-intermediate-like RNA is shielded from processing by a protein(s). Alteration of an AATTTT TAA termination signal to a GCTTTTGC signal activated processing by greater than 100-fold in coupled transcription/processing reactions. A similar difference was found when expression was compared in frog oocytes. No difference in processing was found if the transcripts were made by T7 RNA polymerase in the presence of the nuclear extract, indicating that the different processing effects of the two terminators were dependent on synthesis by polymerase III. The modulation of processing of B1-Alu transcripts and the potential for retrotransposition of B1 and Alu DNA sequences are discussed.

Animals↗

Air embolism-induced lung injury in isolated rat lungs.

Pulmonary air embolism causes physical obstruction of microvasculature and leads to permeability changes, release of mediators, and injury to lung tissue. In this study we employed an isolated perfused rat lung model to investigate the primary and secondary effects produced by infusion of air into the pulmonary artery. Infusion of various doses of air (0.10-0.25 ml) over a 1-min period produced a dose-dependent increase in pulmonary arterial pressure and lung weight gain. In contrast, when a constant air dose was administered over various periods of time (0.25 ml over 0.5-8.0 min), the pulmonary arterial pressure rose to the same extent regardless of the infusion rate, whereas the lung weight gain increased proportionately with the rate of infusion. Total vascular resistance rose from 1.41 +/- 0.04 to 5.04 +/- 0.09 mmHg.ml-1.min in rats given 0.25 ml air over 1 min (n = 14, P less than 0.001), with greater than or equal to 90% of this increase occurring in the arterial segments. Both thromboxane B2 and endothelin concentrations also increased in the perfusate, suggesting their involvement in this increased resistance. Furthermore the pulmonary filtration coefficient increased from 0.21 +/- 0.05 to 1.28 +/- 0.26 g.min-1.cmH2O-1.100 g (n = 8, P less than 0.001), and the protein concentration in lung lavage fluid also rose, indicating lung injury. Leukocyte counts in the perfusate were unaffected by embolization, but chemiluminescent activity was increased, indicating a possible role for activated leukocytes in lung injury induced by air emboli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Terbutaline acts at multiple sites to inhibit bronchoconstriction induced by dry air in canine peripheral airways.

We examined the effect of the beta 2-agonist terbutaline on dry airflow-induced bronchoconstriction (AIB) in the canine lung periphery. Using a wedged bronchoscope technique, collateral resistance (Rcs) and airway wall temperature (Taw) were measured before and after a 2-min exposure to dry air. When sublobar segments were challenged with dry air, Taw fell during challenge (p less than 0.001), and Rcs increased 5 min postchallenge (p less than 0.01). Pretreatment with terbutaline (100 micrograms/kg) reduced the fall induced by dry-air challenge in Taw by 37% and the subsequent rise in Rcs by 87%. Terbutaline significantly reduced the concentrations of thromboxane B2 (TxB2) and prostaglandin D2 (PGD2), and decreased the concentration of epithelial cells recovered in bronchoalveolar lavage fluid 5 min postchallenge. In addition, terbutaline attenuated histamine- and PGD2-induced constriction. Finally, peripheral lung sensitivity (as assessed by delta Rcs/delta Taw) to challenge after treatment with terbutaline was significantly less than that calculated for untreated control animals (p less than 0.05). These data are consistent with the idea that terbutaline attenuates AIB by (1) facilitating replacement of water lost during exposure to dry air, (2) inhibiting mediator production and release from osmosensitive cells, and (3) reducing smooth muscle responsiveness.

Airway Resistance↗

Methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) for advanced TCC of urothelium.

After the introduction of methotrexate, vinblastine, adriamycin and cisplatin combination (M-VAC) chemotherapy for transitional cell carcinoma (TCC) of the urothelium, the reported response and survival rates improved when compared with the previous regimens. From July 1989 to March 1991, 43 consecutive cases of invasive or metastatic TCC that had received at least one course of M-VAC treatment were collected by a computer-assisted search and analyzed. The overall response rate, including complete response (CR) and partial response (PR), was 44% (CR, 16%; PR, 28%). Tumors originating from the renal pelvis or bladder responded better than those from the ureter (kidney, 57%; bladder, 42%; and ureter 30%). Lymph node, soft tissue, lung metastases and local recurrent tumors had a greater chance of response than bone or liver metastases. Although patients from the blackfoot disease endemic area seemed to respond better than those from the nonendemic area, there was no statistically significant survival benefit. The duration of follow-up ranged from nine to 38 months. The length of survival of nonresponders ranged from one month to 19 months (median, eight months; mean, seven months). Ten of the 19 responders relapsed, and the others were still responding. Three patients (7%) survived two years, disease-free. Although the response rate improved, the chance of long-term survival was still unsatisfactory in our study.

Adult↗

Role of platelets in microembolism-induced acute lung injury.

The role of platelets in acute lung injury has not been well defined. In the present study of isolated perfused rat lungs, a significant increase in pulmonary arterial pressure (PAP), lung weight and the lung lavage fluid protein concentration occurred when 3 mL of a CaCl2 suspension (25 mg/mL) was mixed with blood-KHB (Krebs-Henseleit Buffer) perfusate; or when platelets were added instead of blood. However, such an increase was not observed (p > 0.05) when only KHB was used. When a comparatively small amount (0.75 mL) of the CaCl2 suspension (50 mg/mL) was added to the KHB perfusate, PAP, lung weight and the lung lavage protein concentration increased only when PAF (platelet activating factor) and platelets were both added before, but not separately. The above phenomena show that platelets are actively involved in the mechanism of acute lung injury and play an extremely important role in this microembolic model.

Acute Disease↗

Ionic currents of the nodal membrane underlying the fastest saltatory conduction in myelinated giant nerve fibers of the shrimp Penaeus japonicus.

The myelinated giant nerve fiber of the shrimp, Penaeus japonicus, is known to have the fastest velocity of saltatory impulse conduction among all nerve fibers so far studied, owing to its long distances between nodal regions and large diameter. For a better understanding of the basis of this fast conduction, a medial giant fiber of the ventral nerve cord of the shrimp was isolated, and ionic currents of its presynaptic membrane (a functional node) were examined using the sucrose-gap voltage-clamp method. Inward currents induced by depolarizing voltage pulses had a maximum value of 0.5 microA and a reversal potential of 120 mV. These currents were completely suppressed by tetrodotoxin and greatly prolonged by scorpion toxin, suggesting that they are the Na current. Both activation and inactivation kinetics of the Na current were unusually rapid in comparison with those of vertebrate nodes. According to a rough estimation of the excitable area, the density of Na current reached 500 mA/cm2. In many cases, the late outward currents were induced only by depolarizing pulses larger than 50 mV in amplitude. The slope conductance measured from late currents were mostly smaller than that measured from the Na current, suggesting a low density of K channels in the synaptic membrane. These characteristics are in good harmony with the fact that the presynaptic membrane plays a role as functional node in the fastest impulse conduction of this nerve fiber.

Animals↗

Diptheroids and associated infections as a cause of failed instrument stabilization procedures in the lumbar spine.

Between February 1985 and October 1987, the authors identified seven patients with occult lumbar spine infections associated with the presence of spinal fixation hardware. Six of these infections were with organisms of low virulence; four of the seven patients had polymicrobial infections. All of the polymicrobial infections contained a Diptheroid as one of the isolates. Two of the seven patients studied had normal sedimentation rates. All had white blood cell counts less than 12,000 cells. Imaging studies were not helpful with the exception of one case with a positive gallium scan. The diagnoses were supported by clinical presentation, pathologic tissue changes, positive cultures, and response to therapy. Successful therapy was obtained by removal of hardware and treatment with antibiotics.

Anti-Bacterial Agents↗

Cyclooxygenase pathway mediates lung injury induced by phorbol and platelets.

The role of platelets in lung injury has not been well defined. In the present study of isolated perfused rat lungs, phorbol myristate acetate (PMA; 0.15 microgram/ml) or platelets (6.7 X 10(4)/ml) alone did not discernibly change the pulmonary arterial pressure (PAP) or lung weight (LW). However, the combination of platelets and PMA drastically increased the PAP and LW (delta PAP 26.2 +/- 1.0 mmHg, delta LW 2.7 +/- 0.4 g). delta PAP was positively correlated with the increase in thromboxane B2 produced by infusion of platelets and PMA (thromboxane B2 = 35.6 + 0.97 delta PAP, r = 0.67, P less than 0.01). The hypertension and edema formation induced by PMA and platelets were strongly attenuated by indomethacin, an inhibitor of platelet cyclooxygenase (delta PAP 5.6 +/- 2.0 mmHg, P less than 0.001; delta LW 0.0 +/- 0.1 g, P less than 0.001), and by imidazole, an inhibitor of thromboxane A2 synthase (PAP 8.0 +/- 2.5 mmHg, P less than 0.001; LW 0.0 +/- 0.3 g, P less than 0.01). Inactivation of platelet lipoxygenase with nordihydroguaiaretic acid mildly depressed pulmonary pressure but did not affect delta LW (delta PAP 18.9 +/- 1.6 mmHg, P less than 0.05; delta LW 3.1 +/- 0.3 g, P greater than 0.05). In vitro experiments showed that the capacity of platelets to release oxygen radicals was only 2.6% of that found for granulocytes. These results suggest that platelets may be activated by PMA to increase PAP and vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pleomorphic adenoma of the trachea: report of two cases.

Two unusual cases of pleomorphic adenoma (benign mixed tumor) of the trachea were found in a 56-year-old woman and a 20-year-old man. Both patients had been initially treated for presumed bronchial asthma for 5 years and 4 years, respectively. Pulmonary function tests in each showed typical extrathoracic obstruction. The diagnosis of tracheal lesions in both cases was based principally on the following: 1) dyspnea without complete remission over an extended period of time following initial examination; 2) marked retraction of the supraclavicular and suprasternal notches during inspiration with stridor on physical examination; and 3) a high degree of suspicion. Large tumors were found within the air column of the trachea by soft tissue density X-ray films and electroradiographs of the neck, CT scans of the neck and mediastinum in each patient revealed that the tumor originated from the membranous layers of the trachea in the woman and the posterolateral wall of the trachea in the man. Fiberoptic bronchoscopy confirmed the clinical diagnosis. Both cases were successfully treated by segmental resection of the trachea with end-to-end anastomosis.

Adult↗

[Unusual presentations of angiomyolipoma].

Angiomyolipoma is an uncommon benign tumor of the kidney. The tumor is composed of fat, smooth muscle, and blood vessels. The same pathological entity can appear in two clinically different forms, with or without tuberous sclerosis. We present two cases of renal angiomyolipomas with unusual manifestations. One was associated with tuberous sclerosis and both had the presentation of acute abdomen. Case one presented with epilepsy, angiofibroma, subungual fibroma, periventricular calcification, and bilateral renal angiomyolipomas. Tuberous sclerosis is characterized by these findings. Both cases had spontaneous hemorrhage with hypovolemic shock. Massive hemorrhage resulting in shock is uncommon and the incidence has been estimated to be about 10 per cent. In fact, many angiomyolipomas are clinically occult. The size of the tumor correlates well with the presence or absence of symptoms which include microhematuria, flank pain, hypertension and urinary tract infection. Abdominal CT is the preferred modality for diagnosis of angiomyolipoma. The most important finding is the presence of an intrarenal tumor with fat component which is recognized as a relative low density on CT. Our patients were hospitalized under the impression of angiomyolipoma after the CT study. In addition, the CT defined either the size of the tumor or the extension of the hemorrhage. Although many believe that renal angiography is not sufficient by itself to establish the diagnosis of angiomyolipoma, occasionally it is mandatory in the management of the tumor. The management is decided by two factors, the size of tumor and the clinical presentation. The attitude of management should include conservative treatment with regular follow-up, selective arterial embolization, enucleation, and partial or total nephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of mandatory seat belt legislation on self-reported seat belt use among male and female college students.

The effect of seat belt legislation on self-reported seat belt use among male and female college students was investigated. Questionnaires inquiring about seat belt use were administered to college students on three separate occasions: (i) two months prior to the time a mandatory seat belt law went into effect, (ii) two months after the law went into effect, and (iii) 16 months after the law went into effect. Reported seat belt use increased significantly for male and female college students two months after the law took effect. At 16 months postlaw, reported seat belt use remained high for female students but declined almost to the prelaw level for males. Possible reasons offered for these findings are that male college students may be more resistant to having their behavior regulated and, therefore, less likely to internalize changes forced on them, and college-age males may be more inclined to engage in risk-taking behavior than college-age females. The importance of considering males and females separately with respect to seat belt use and interventions designed to increase seat belt use is discussed.

Adult↗

Correlation between cardiopulmonary changes and severity of acute lung injury in dogs.

In an attempt to determine the physiologic parameters that best correlate with severity of lung edema (wet/dry [W/D] weight), we serially monitored multiple cardiopulmonary hemodynamics, airway pressure, and blood gases on both 100% oxygen and room air after graded infusions of oleic acid (OA) in dogs. We found significant increases in the intrapulmonary shunt fraction (Qsp/Qt), mean pulmonary arterial pressure (MPAP), pulmonary (PVR) and systemic vascular resistance (SVR), alveolar-arterial PO2 difference (P[A-a] O2), and peak airway pressure (Paw), but decreases in PaO2 and pH. These cardiopulmonary hemodynamic changes were similar to those found in adult respiratory distress syndrome (ARDS). This study showed that Qsp/Qt (r = .72, p less than .001), PaO2 (r = -.60, p less than .01), P(A-a)O2 (r = .55, p less than .01), pH (r = -.55, p less than .01), MPAP (r = .50, p less than .05) and Paw (r = .49, p less than .05) significantly correlated linearly with W/D. The significant correlation is not high enough clinically to predict the severity of acute permeability pulmonary edema considering only one parameter of cardiopulmonary hemodynamic change. Therefore, we propose the possible prediction of the severity of ARDS by considering all of the above hemodynamic changes together with Paw or dynamic compliance.

Acute Disease↗

High lumbar disc degeneration. Incidence and etiology.

Three hundred seventy-nine consecutive magnetic resonance images (MRIs) with dual-echo images of the entire lumbar spine were reviewed by the authors. All 379 patients presented with back pain and/or leg pain; they were interviewed and examined. Pain drawings were completed by all. There were 42 patients (11.1%) with disc pathologies involving T12-L1, L1-2, and/or L2-3 levels. Six patients (1.6%) had isolated disc degeneration and/or herniations limited only to these high lumbar segments. The remaining 36 patients had degenerative changes of the higher discs with variable involvement of the lower lumbar discs. Out of 12 spondylolistheses of L5 on S1, 7 had high disc pathologies at one or more levels presenting as skipped lesions; more severe high disc lesions were noted in Grade II slips. Isolated high disc degeneration is often associated with pre-existing abnormalities such as end-plate defects, Scheuermann's disease, limbus vertebra, and so forth, and stressful cumulative work activities such as in construction workers, airplane mechanics, and so forth. High disc degeneration was noted above or below previous fractures. High disc involvement with diffuse changes in lower lumbar spine was more commonly found in ascending fashion in older age groups, and in patients who have had previous lower lumbar spine surgeries, prior fusions in particular. Our findings suggest that altered mechanics are associated with the high lumbar disc pathologies.

Adult↗

Metabolic bone disease in lumbar pseudarthrosis.

Pseudarthrosis occurs in many patients who undergo lumbar spine fusion and it has been suggested that abnormalities of bone metabolism contribute to it. The authors evaluated 47 patients with pseudarthrosis for metabolic bone disease. Symptomatic patients with pseudarthrosis underwent metabolic bone evaluation. Abnormal results of laboratory tests were found in 7 patients (14.9%): 3 low or borderline 1,25 dihydroxy vitamin D3, 2 elevated 24-hour urine calcium, and 2 low serum testosterone. None of these abnormalities correlated with other clinical findings. Bone density was low in 14 of 24 patients in whom it was measured. Low values did not correlate with smoking or abnormal laboratory values. Metabolic bone abnormalities do not appear to play a frequent or significant role in pseudarthrosis after attempted lumbar spine fusion.

Adult↗

Protective effect of pentoxifylline on phorbol myristate acetate-induced acute lung injury in rats.

The pathogenesis of adult respiratory distress syndrome (ARDS) is not clear, and its therapy is still a problem. Pentoxifylline, a methylxanthine derivative, can inhibit phosphodiesterase activity and thus increase the intracellular cAMP. There are also some hypotheses that pentoxifylline can attenuate pulmonary edema. In order to evaluate the protective effect of pentoxifylline in acute lung injury, we set up an isolated lung perfusion model in rats and induced experimental acute lung injury similar to ARDS by intravenously infused phorbol myristate acetate (PMA) 7.5 micrograms/300 g body weight. Four groups of experimental rats were studied: group 1, normal control group, neither PMA nor pentoxifylline was used in 6 rats; group 2 (acute lung injury group), only PMA was infused in 8 rats; group 3 (protective group), pentoxifylline 100 mg/300 g body weight was given intravenously before PMA infusion in 6 rats; group 4, only pentoxifylline was given in 6 rats. Pulmonary arterial pressure (PAP) as well as lung weight changes were recorded before and 5, 10, 15, 20 and 25 minutes after drug injection. Bronchial lavage fluids were then measured for albumin concentration. We found that PAP was strikingly increased in group 2 (54.0 +/- 8.8 mmHg), but the increase was significantly reduced in group 3 (29.8 +/- 5.8 mmHg, p less than 0.001). Similarly, the lung weight gain was markedly increased in group 2 (4.69 +/- 1.28 g), but was significantly attenuated in group 3 (1.25 +/- 1.60 g, p less than 0.001). There was no apparent change in PAP and lung weight gain throughout the entire procedure in groups 1 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The protective effect of mepacrine on acute lung edema induced by phorbol myristate acetate in rats.

A good model of adult respiratory distress syndrome is lung injury induced by phorbol myristate acetate (PMA). In the present study we examined the effect of mepacrine, an inhibitor of phospholipase A2, on lung injury induced by PMA in isolated blood-perfused rat lungs. In the isolated lung, saline (1 ml) or mepacrine (75 microM) alone in the perfusion system did not discernibly change the pulmonary arterial pressure (PAP) and lung weight (LW). After administration of PMA (0.16 micrograms/ml), severe hypertension and lung edema developed (delta PAP = 40.1 +/- 6.0 mmHg, p less than 0.001; delta LW = 5.5 +/- 0.7 g, p less than 0.001). Whereas, the addition of mepacrine (75 microM) prevented PMA-induced lung edema and pulmonary hypertension (delta PAP = 4.7 +/- 2.2 mmHg, delta LW = 0.2 +/- 0.2 g). To further elucidate the protective mechanism of mepacrine on lung injury, a vasodilator (nitroprusside) was given to decrease PAP levels to +6 mmHg from baseline values in the PMA group, as well as in the mepacrine-pretreated PMA (MPMA) group. During a subsequent venous pressure challenge, severe lung injury developed in the PMA group (delta LW = 9.5 +/- 2.1 g, p less than 0.001). However, with the same venous pressure challenge in the MPMA the lung weight was markedly less than that of the PMA group (delta LW = 1.0 +/- 0.2 g). Histologic findings examined by light microscopy presented intraalveolar hemorrhage and fluid accumulation, disruption of vascular basements and alveolar septa, and aggregation of inflammatory cells within the parenchyma in the lungs of the PMA group. In the MPMA group there was no evidence of intraalveolar hemorrhage and alveolar fluid accumulation, however, the occasional presence of granulocytes in the parenchyma and slight interstitial edema were still observed. In addition, depressed the chemiluminescence release from PMA activated granulocytes which were in a dose-dependent manner in vitro. These observations suggest that mepacrine inhibits PMA-induced lung injury chiefly by protection of vascular permeability. The mechanism of the protection may be due to the inhibition of oxygen radicals released from activated neutrophils and the reduction of neutrophil chemotaxis.

Animals↗

Dimethylthiourea decreases acute pulmonary edema induced by phorbol myristate acetate in isolated blood-perfused lung of the rat.

Acute pulmonary edema can be induced by phorbol myristate acetate (PMA). Oxygen radicals released from the neutrophils have been considered to play an important role in the pathogenesis of PMA-induced pulmonary edema. In the present experiment, we studied the effect of dimethylthiourea (DMTU) on PMA-induced pulmonary injuries in isolated perfused lungs of rats. DMTU is a potent scavenger of the hydroxyl radical and hydrogen peroxide. PMA infusion into the isolated lung increased pulmonary arterial pressure (delta PAP) by 37.8 +/- 3.9 mmHg. The lung weight gain (LWG) and lavage albumin concentration (LAC) amounted to 6.2 +/- 1.2 g and 102.0 +/- 22.9 mg/dl, respectively. DMTU (100 mM) pretreatment significantly reduced the PAP increase (delta PAP = 4.6 +/- 0.8 mmHg, p less than 0.001), LWG (0.3 +/- 0.1 g, p less than 0.01) and LAC (25.3 +/- 1.7 mg/dl, p less than 0.01). Additional in vitro experiments demonstrated that DMTU depressed the chemiluminescence released from neutrophils activated by PMA (17.9 +/- 2.6 mV.min to 2.6 +/- 0.5 mV.min, p less than 0.01). The results suggest that DMTU, a scavenger of toxic radicals, decreases the lung edema through both attenuation of pulmonary hypertension and protection of vascular permeability from PMA injury.

Acute Disease↗