bluuebunny/crossref_metadata_2025 huggingface dataset:
Time course of flow-induced vasodilation in skeletal muscle: contributions of dilator and constrictor mechanisms
Authors: Shipley Robert D. , Kim Se Jeong , Muller-Delp Judy M.
Published: December 2004

The purpose of this study was to determine the time course of flow-induced vasodilation in soleus and gastrocnemius muscle arterioles and the mechanisms that underlie vasodilatory responses to an increase in intraluminal flow. Vasodilation was assessed during 20 min of continuous exposure to intraluminal flow. Both soleus and gastrocnemius muscle arterioles dilated in response to flow, although the magnitude of vasodilation was greater in arterioles from the gastrocnemius muscle. Neither blockade of nitric oxide synthase with NG-nitro-l-arginine methyl ester (l-NAME) nor blockade of cyclooxygenase with indomethacin inhibited the initial vasodilation (0–2 min) in arterioles from either muscle. In contrast, vasodilation to sustained exposure to flow (2–20 min) was eliminated by treatment with l-NAME in arterioles from both muscles. Both depolarization with 40 mM KCl and blockade of Ca2+-activated K+channels inhibited the initial flow-induced dilation, and the inhibition was greater in gastrocnemius muscle arterioles than soleus muscle arterioles. In the presence of l-NAME, prolonged exposure to flow resulted in constriction in soleus and gastrocnemius muscle arterioles. This constriction was abolished by endothelin receptor blockade. These results indicate that the time course and magnitude of flow-induced vasodilation differs between arterioles from soleus and gastrocnemius muscles. The immediate response to increased flow is greater in gastrocnemius muscle arterioles and involves activation of K+channels. In arterioles from both soleus and gastrocnemius muscles, vasodilation to sustained flow exposure occurs primarily through production of nitric oxide. In the absence of nitric oxide, sustained exposure to flow results in pronounced constriction that is mediated by endothelin.
Muscle metaboreflex modulates the arterial baroreflex dynamic effects on peripheral vascular conductance in humans
Authors: Ichinose Masashi , Nishiyasu Takeshi
Published: December 2004

We aimed to investigate the interaction between the arterial baroreflex and muscle metaboreflex [as reflected by alterations in the dynamic responses shown by leg blood flow (LBF: by the ultrasound Doppler method), leg vascular conductance (LVC), mean arterial blood pressure (MAP), and heart rate (HR)] in humans. In 12 healthy subjects (10 men and 2 women), who performed sustained 1-min handgrip exercise at 50% maximal voluntary contraction followed immediately by an imposed postexercise muscle ischemia (PEMI), 5-s periods of neck pressure (NP; 50 mmHg) or neck suction (NS; −60 mmHg) were used to evaluate carotid baroreflex function both at rest (Con) and during PEMI. First, the decreases in LVC and LBF and the augmentation of MAP elicited by NP were all greater during PEMI than in Con (ΔLVC, −1.2 ± 0.2 vs. −1.9 ± 0.2 ml·min−1·mmHg−1; ΔLBF, −97.3 ± 11.2 vs. −177.0 ± 21.8 ml/min; ΔMAP, 6.7 ± 1.2 vs. 11.5 ± 1.4 mmHg, Con vs. PEMI; each P < 0.05). Second, in Con, NS significantly increased both LVC and LBF (ΔLVC, 0.9 ± 0.2 ml·min−1·mmHg−1; ΔLBF, 46.6 ± 9.8 ml/min; significant change from baseline: each P < 0.05), and, whereas during PEMI no significant increases in LVC and LBF occurred during NS itself (ΔLVC, 0.2 ± 0.1 ml·min−1·mmHg−1; ΔLBF, 10.8 ± 9.6 ml/min; each P > 0.05), a decrease was evident in each parameters at 5 s after the cessation of NS. Third, during PEMI, the decrease in MAP elicited by NS was smaller (ΔMAP, −8.4 ± 1.0 vs. −5.8 ± 0.4 mmHg, Con vs. PEMI; P < 0.05), and it recovered to its initial level more quickly after NS (vs. Con). Finally, however, the HR responses to NS and NP were not different between PEMI and Con. These results suggest that during muscle metaboreflex activation in humans, the arterial baroreflex dynamic effect on peripheral vascular conductance is modulated, as exemplified by 1) an augmentation of the NP-induced LVC decrease, and 2) a loss of the NS-induced LVC increase.
Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling
Authors: Johnson John M. , Yen Tony C. , Zhao Kun , Kosiba Wojciech A.
Published: December 2004

Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29°C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (−14 ± 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 ± 7.7%) but did not affect the response at 30 min (−30.6 ± 9% control, −38.9 ± 6.9% bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (−14.3 ± 4.2% control) to vasodilation (+26.3 ± 12.1% YP), without a significant effect on the 30-min response (−26.7 ± 6.1% YP, −43.2 ± 6.5% control; both P < 0.05, P > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction ( P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (−20.1 ± 6.4% control) to one of vasodilation (+213.4 ± 87.0% Emla), whereas the final levels did not differ significantly (−37.7 ± 10.1% control, −37.2 ± 8.7% Emla; both P < 0.05, P > 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves.
Effects of BDM, [Ca2+]o, and temperature on the dynamic stiffness of quiescent cardiac trabeculae from rat
Authors: Kirton R. S. , Taberner A. J. , Nielsen P. M. F. , Young A. A. , Loiselle D. S.
Published: December 2004

Studies of the passive mechanical properties of cardiac tissue have traditionally been conducted at subphysiological temperatures and various concentrations of extracellular Ca2+ ([Ca2+]o). More recently, the negative inotropic agent 2,3-butanedione monoxime (BDM) has been used. However, there remains a lack of data regarding the influence of temperature, Ca2+, and BDM on the passive mechanical properties of cardiac tissue. We have used the dynamic stiffness technique, a sensitive measurement of cross-bridge activity, in which minute (∼0.2% of muscle length) sinusoidal perturbations are applied at various frequencies (0.2–100 Hz) to quiescent, viable right ventricular rat trabeculae at two temperatures (20°C and 26°C) and at two [Ca2+]o (0.5 and 1.25 mM) in the presence and absence of BDM (20 mM). The stiffness spectra (amplitude and phase) were sensitive to temperature and [Ca2+]o in the absence of BDM but insensitive in the presence of BDM. From the index of cross-bridge cycling (the ratio of high- to low-frequency stiffness amplitude), we infer that BDM inhibits a small degree of spontaneous sarcomere activity, thereby allowing the true passive properties of trabeculae to be determined. In the absence of BDM, the extent of spontaneous sarcomere activity decreases with increasing temperature. We caution that the measured mechanical properties of passive cardiac tissue are critically dependent on the experimental conditions under which they are measured. Experiments must be performed at sufficiently high temperatures (>25°C) to ensure a low resting concentration of intracellular Ca2+ or in the presence of an inhibitor of cross-bridge cycling.
Elevated plasma viscosity in extreme hemodilution increases perivascular nitric oxide concentration and microvascular perfusion
Authors: Tsai Amy G. , Acero Cesar , Nance Patricia R. , Cabrales Pedro , Frangos John A. , Buerk Donald G. , Intaglietta Marcos
Published: December 2004

We tested the hypothesis that high-viscosity (HV) plasma in extreme hemodilution causes wall shear stress to be greater than low-viscosity (LV) plasma, leading to enhanced production of nitric oxide (NO). The perivascular concentration of NO was measured in arterioles and venules and the tissue of the hamster chamber window model, subjected to acute extreme hemodilution, with a hematocrit (Hct) of 11% using Dextran 500 ( n = 6) or Dextran 70 ( n = 5) with final plasma viscosities of 1.99 ± 0.11 and 1.33 ± 0.04 cp, respectively. HV plasma significantly increased the periarteriolar, perivenular, and tissue NO concentration by 2.0, 1.9, and 1.4 times the control ( n = 7). The NO concentration with LV plasma was not statistically different from control. Arteriolar shear stress was significantly increased in HV plasma relative to LV plasma in arterioles but not in venules. Aortic endothelial NO synthase (eNOS) protein expression was increased with HV plasma but not with LV plasma. There was a weak correlation between perivascular NO concentration and the locally calculated shear stress induced by the procedures, when blood viscosity was corrected according to Hct values previously determined in studies of microvascular Hct distribution. The finding that the periarteriolar and venular NO concentration in HV plasma was the same although arteriolar shear stress was significantly greater than venular shear stress maybe be due to differences in vessel wall metabolism between arterioles and venules and the presence of NO transport through the blood stream in the microcirculation. Results support the concept that in extreme hemodilution HV plasma maintains functional capillary density through a NO-mediated vasodilatation.
Subfornical organ disconnection alters Fos expression in the lamina terminalis, supraoptic nucleus, and area postrema after intragastric hypertonic NaCl
Authors: Freece Julia A. , Van Bebber Julie E. , Zierath Dannielle K. , Fitts Douglas A.
Published: December 2004

The lamina terminalis was severed by a horizontal knife cut through the anterior commissure to determine the effects of a disconnection of the subfornical organ (SFO) on drinking and Fos-like immunoreactivity (Fos-ir) in the rat brain in response to an intragastric load of hypertonic saline (5 ml/kg of 1.5 M NaCl by gavage). After an initial load, knife-cut rats drank significantly less water than sham-cut rats, thus confirming a role for the SFO in osmotic drinking. After a second load at least 1 wk later, the rats were not allowed to drink after the gavage and were perfused for analysis of Fos-ir at 90 min. Compared with sham-cut rats, the knife-cut rats displayed significantly elevated Fos-ir in the main body of the SFO, in the dorsal cap of the organum vasculosum laminae terminalis, and in the ventral median preoptic nucleus after the hypertonic load. The knife cut significantly decreased Fos-ir in the supraoptic nucleus. Fos-ir was expressed mainly in the midcoronal and caudal parts of the area postrema of sham-cut rats, and this expression was greatly reduced in knife-cut rats. These findings strengthen the case for the presence of independently functioning osmoreceptors within the SFO and suggest that the structures of the lamina terminalis provide mutual inhibition during hypernatremia. They also demonstrate that the Fos-ir in the area postrema after intragastric osmotic loading is heavily dependent on the intact connectivity of the SFO.
Factorial scopes of cardio-metabolic variables remain constant with changes in body temperature in the varanid lizard,Varanus rosenbergi
Authors: Clark T. D. , Wang T. , Butler P. J. , Frappell P. B.
Published: December 2004

The majority of information concerning the cardio-metabolic performance of varanids during exercise is limited to a few species at their preferred body temperature (Tb) even though, being ectotherms, varanids naturally experience rather large changes in Tb. Although it is well established that absolute aerobic scope declines with decreasing Tb, it is not known whether changes in cardiac output (V̇b) and/or tissue oxygen extraction, (CaO2− Cv�[Formula: see text]), are in proportion to the rate of oxygen consumption (V̇o2). To test this, we studied six Rosenberg's goannas ( Varanus rosenbergi) while at rest and while maximally exercising on a treadmill both at 25 and 36°C. During maximum exercise both at 25 and 36°C, mass-specific rate of oxygen consumption (V̇o2kg) increased with an absolute scope of 8.5 ml min−1kg−1and 15.7 ml min−1kg−1, respectively. Interestingly, the factorial aerobic scope was temperature-independent and remained at 7.0 which, at each Tb, was primarily the result of an increase in V̇bkg, governed by approximate twofold increases both in heart rate ( fH) and cardiac stroke volume (VSkg). Both at 25°C and 36°C, the increase in V̇bkgalone was not sufficient to provide all of the additional oxygen required to attain maximal V̇o2kg, as indicated by a decrease in the blood convection requirement V̇bkg/V̇o2kg; hence, there was a compensatory twofold increase in (CaO2− [Formula: see text]). Although associated with an increase in hemoglobin-oxygen affinity, a decrease in Tbdid not impair unloading of oxygen at the tissues and act to reduce (CaO2− Cv�[Formula: see text]); both CaO2and Cv�[Formula: see text] were maintained across Tb. The change in V̇o2kgwith Tb, therefore, is solely reliant on the thermal dependence of V̇bkg. Maintaining a high factorial aerobic scope across a range of Tbconfers an advantage in that cooler animals can achieve higher absolute aerobic scopes and presumably improved aerobic performance than would otherwise be achievable.
Bicarbonate secretion plays a role in chloride and water absorption of the European flounder intestine
Authors: Grosell M. , Wood C. M. , Wilson R. W. , Bury N. R. , Hogstrand C. , Rankin C. , Jensen F. B.
Published: December 2004

Experiments performed on isolated intestinal segments from the marine teleost fish, the European flounder ( Platichthys flesus), revealed that the intestinal epithelium is capable of secondary active HCO3−secretion in the order of 0.2–0.3 μmol·cm−2·h−1against an apparent electrochemical gradient. The HCO3−secretion occurs via anion exchange, is dependent on mucosal Cl−, results in very high mucosal HCO3−concentrations, and contributes significantly to Cl−and fluid absorption. This present study was conducted under in vivo-like conditions, with mucosal saline resembling intestinal fluids in vivo. These conditions result in a transepithelial potential of −16.2 mV (serosal side negative), which is very different from the −2.2 mV observed under symmetrical conditions. Under these conditions, we found a significant part of the HCO3−secretion is fueled by endogenous epithelial CO2hydration mediated by carbonic anhydrase because acetazolamide (10−4M) was found to inhibit HCO3−secretion and removal of serosal CO2was found not to influence HCO3−secretion. Reversal of the epithelial electrochemical gradient for Cl−(removal of serosal Cl−) and elevation of serosal HCO3−resulted in enhanced HCO3−secretion and enhanced Cl−and fluid absorption. Cl−absorption via an anion exchange system appears to partly drive fluid absorption across the intestine in the absence of net Na+absorption.
Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding in Siberian hamsters
Authors: Keen-Rhinehart Erin , Bartness Timothy J.
Published: December 2004

Fasting triggers many effects, including increases in circulating concentrations of ghrelin, a primarily stomach-derived orexigenic hormone. Exogenous ghrelin treatment stimulates food intake, implicating it in fasting-induced increases in feeding, a consummatory ingestive behavior. In Siberian hamsters, fasting also stimulates appetitive ingestive behaviors such as foraging and food hoarding. Therefore, we tested whether systemic ghrelin injections (3, 30, and 200 mg/kg) would stimulate these appetitive behaviors using a running wheel-based food delivery system coupled with simulated burrow housing. We also measured active ghrelin plasma concentrations after exogenous ghrelin treatment and compared them to those associated with fasting. Hamsters had the following: 1) no running wheel access, free food; 2) running wheel access, free food; or 3) foraging requirement (10 revolutions/pellet), no free food. Ghrelin stimulated foraging at 0–1, 2–4, and 4–24 h postinjection but failed to affect wheel running activity not coupled to food. Ghrelin stimulated food intake initially (200–350%, first 4 h) across all groups; however, in hamsters with a foraging requirement, ghrelin also stimulated food intake 4–24 h postinjection (200–250%). Ghrelin stimulated food hoarding 2–72 h postinjection (100–300%), most markedly 2–4 h postinjection in animals lacking a foraging requirement (635%). Fasting increased plasma active ghrelin concentrations in a time-dependent fashion, with the 3- and 30-mg/kg dose creating concentrations of the peptide comparable to those induced by 24–48 h of fasting. Collectively, these data suggest that exogenous ghrelin, similar to fasting, increases appetitive behaviors (foraging, hoarding) by Siberian hamsters, but dissimilar to fasting in this species, stimulates food intake.
Virus Overlay Protein Binding Assay (VOPBA) Reveals Serotype Specific Heterogeneity of Dengue Virus Binding Proteins on HepG2 Human Liver Cells
Authors: Jindadamrongwech Sumalee , Smith Duncan R.
Published: December 2004

Objective: This study sought to investigate the presence of dengue virus binding proteins expressed on the surface of HepG2 cells and to determine if there were serotype specific differences in binding. Methods: HepG2 cell membrane proteins were extracted and separated by SDS-PAGE, transferred to nitrocellulose membranes and incubated with dengue virus serotypes 2, 3 and 4 under varying hybridization conditions. The positions of dengue virus binding proteins were established with a pan-specific anti-dengue virus monoclonal antibody. Results: Dengue virus binding proteins were seen at approximately 78–80, 90, 98, and 102 kD for dengue serotype 2, 90, 130 and 182 kD for dengue serotype 3, and 90 and 130 kD for dengue serotype 4. Binding of the serotypes 3 and 4 was significantly altered by the hybridization conditions, while serotype 2 was affected to a lesser extent. Conclusions: The virus overlay assay used here provides further evidence that there is a serotype specific component regulating the entry of the dengue virus into cells. Given that several virus binding proteins are seen for each serotype, multiple proteins may be required to facilitate the entry of the virus into some cell types.
Krypton Laser Membranotomy for Premacular Hemorrhage
Authors: Chen Yung-Jen , Kou Hsi-Kung
Published: December 2004

Background: To evaluate the safety and effectiveness of krypton laser membranotomy. Methods: Eleven patients (12 eyes) with premacular hemorrhage were enrolled from April 1998 to November 2002. The causes of premacular hemorrhage were proliferative diabetic retinopathy (7 patients, 8 eyes), Valsalva retinopathy (3 patients) and leukemia (1 eye). Krypton laser was used to create a membranotomy on the sloping edge of the premacular hemorrhage. Five eyes with proliferative diabetic retinopathy were treated with inferior panretinal photocoagulation and laser membranotomy simultaneously. After intravitreal dispersion of premacular blood, fundus examinations were performed in all eyes and fluorescein angiography in 5 patients to evaluate the retinal damage. Results: Vision was improved within 2 weeks after surgery in all eyes with premacular hemorrhage, which received krypton laser membranotomy. No retinal damage was seen at the site of membranotomy. No eye needed vitrectomy postoperatively during the follow-up (mean, 17 months). Conclusion: Krypton laser membranotomy appears to be a safe and simple alternative procedure for treating selected cases of premacular hemorrhage. Further trials are necessary to evaluate its benefit.
Treatment Options in the Management of Choroidal Metastases
Authors: Amer Radgonde , Pe’er Jacob , Chowers Itay , Anteby Irene
Published: December 2004

We performed a retrospective study of 40 consecutive patients (50 eyes) treated for choroidal metastases of solid systemic malignancies in order to evaluate treatment results. Patients received either systemic or local therapy or a combination of both. The most common primary tumor was breast carcinoma (62.5%). Systemic chemotherapy alone was used in 13.3% of eyes, local therapy alone in 44.4%, and a combination of both in 42.2% of eyes. Local treatment modalities included brachytherapy, external beam irradiation, and laser photocoagulation. Complete regression of the choroidal metastases was seen in 57.8% of eyes, partial regression in 15.6 and no response in 4.4%; 22.2% were not available for re-evaluation. We have concluded that the treatment modality in patients with metastatic ocular disease should be individually tailored. When ocular metastases are concurrent with widespread metastatic disease, systemic chemotherapy alone or in combination with local therapy is reasonable. In patients manifesting metastases in the eyes alone, local therapy modalities may be safe, allowing conservation of visual functions with minimal systemic morbidity.
TGFBI Gene Mutation Analysis in Families with Hereditary Corneal Dystrophies from Ukraine
Authors: Pampukha V.M. , Drozhyna G.I. , Livshits L.A.
Published: December 2004

In our study, 5 previously reported mutations of the TGFBI gene – R124C, R124H, R124L (exon 4), R555W, R555Q (exon 12) – were analyzed using polymerase chain reaction followed by restriction digestion in 48 individuals from 19 unrelated families with different forms of corneal dystrophy from different regions of Ukraine. The R555W mutation was detected in 6 patients from 4 families with granular corneal dystrophy. The R124C mutation was detected in 1 unaffected 10-year-old individual and in 24 patients from 8 families with lattice corneal dystrophy. As far as the R124C mutation detected in 1 patient with clinically diagnosed Reis-Bucklers corneal dystrophy is concerned, we concluded that this patient was misdiagnosed. The obtained results show that TGFBI gene mutation analysis is important as well for the early differential diagnosis of corneal dystrophies and genetic consulting in high-risk families.
Changes in Voice and Subjective Sensations during a 45-min Vocal Loading Test in Female Subjects with Vocal Training
Authors: Laukkanen Anne-Maria , Järvinen Kati , Artkoski Marjanna , Waaramaa-Mäki-Kulmala Teija , Kankare Elina , Sippola Saija , Syrjä Tiina , Salo Arla
Published: December 2004

Twenty-four females (mean age 38 years) with varying amounts of vocal training read aloud from a book for 45 min (70 dB at 40 cm distance). Symptoms of the throat and voice were ascertained with a questionnaire before, during and after the test. Fundamental frequency (F₀) and sound pressure level (SPL) were measured. The alpha ratio describing the spectrum slope was calculated: SPL in the range 1–5 kHz minus SPL in the range 50 Hz–1 kHz. All measurements were made for the 1st, 5th, 15th, 30th and the 45th min of loading and for text reading before and after it. F₀, SPL and alpha values rose during the test, which may indicate adaptation to loading. During the first 5 min, however, these parameters showed a decreasing tendency, possibly reflecting warm-up. Subjects with more vocal training had a lower F₀ in the loading test. SPL seemed to reflect variation of symptoms during loading. Changes in acoustic parameters did not distinguish between subjects with most and fewest symptoms of fatigue in this test.
The Perception of Speech Naturalness of Post-Therapeutic and Altered Auditory Feedback Speech of Adults with Mild and Severe Stuttering
Authors: Stuart Andrew , Kalinowski Joseph
Published: December 2004

The effect of therapy and altered auditory feedback (AAF) on the perception of speech naturalness of people who stutter was examined. Thirty-five naïve young adult listeners rated speech samples from fluent speakers and individuals who stutter. Samples came from normal adults who spoke Standard American English; adults with mild or severe stuttering who spoke under conditions of non-altered feedback (NAF), delayed auditory feedback (DAF), and frequency-altered feedback (FAF); and adults with mild or severe stuttering prior to and following successful completion of a Precision Fluency Shaping Program. Speech produced under AAF was rated as significantly more natural sounding than speech from the same individuals under NAF (p < 0.0001). Speech produced during FAF was judged to be more natural sounding than that produced during DAF for those with mild (p = 0.003) and severe (p < 0.0001) stuttering. Mild stuttered speech was judged to have more natural-sounding speech than severe stuttered speech during AAF (p < 0.0001). Speech from individuals following therapy was rated significatly less natural sounding than that from individuals during AAF for both mild and severe stuttering (p < 0.0001). The speech of individuals prior to therapy was rated significantly more natural than their speech produced after therapy (p < 0.0001). Speech from normal fluent speakers was rated as significantly more natural sounding than all samples produced from the individuals who stutter (p < 0.0001). These findings support the contention that AAF benefits those who stutter through a reduction of stuttering with a gain in perceived speech naturalness.
Acoustic Analysis of Speech Tasks Performed by Three Individuals with Spinocerebellar Ataxia
Authors: Schalling Ellika , Hartelius Lena
Published: December 2004

A number of speech tasks produced by three female subjects with different types of genetically diagnosed spinocerebellar ataxia and with mild dysarthria were investigated using acoustic instrumentation. All subjects showed a number of signs of decreased speech rate, increased pause duration, increased and more variable durations of alternating motion rate, sequential motion rate syllables and inter-stress intervals in addition to vocal instability. These signs were consistent with the perceptual judgment of ataxic dysarthria. Furthermore, the severity of impairment found using these speech analysis methods seemed to correspond to the general severity of the disease and the duration of the illness in these few subjects. The tasks studied appeared to be relevant and suitable for acoustic analyses as they did reveal deviations in the speech of the subjects compared with controls.
Changes in the Epithelium of the Vaginal Complex during the Estrous Cycle of the Marsupial Monodelphis domestica
Authors: Kress Annetrudi , Regli Christian , Spornitz Udo M. , Morson Gianni
Published: December 2004

The four stages of the estrous cycle in Monodelphis domestica, namely proestrus, estrus, postestrus and the transitional metestrus, were analyzed with the scanning electron microscope and compared with the results of the previously published transmission electron-microscopic paper [Cells Tissues Organs 2002;172:276–296]. During the estrous cycle the vaginal epithelium undergoes dramatic changes from a nonkeratinized to a highly keratinized epithelium. The predominant feature of proestrus with the beginning of keratinization is the presence of polygonal flat cells with pavement-like appearance, bordered by raised ridges and covered with microvilli. The epithelium is fully keratinized in estrus, and the superficial layers overlap like shingles. Many cells are still densely covered by microvilli, whereas others develop a complex pattern of microridges. In postestrus different epithelial structures are revealed depending on the actual stage of desquamation. In early postestrus surface cells resemble those present during estrus. In late postestrus, when only few keratinized cells are left, the nonkeratinized cells become exposed to the lumen through desquamation. These cells border the lumen during metestrus, a cycle stage during which numerous leukocytes migrate into the vaginal canal. A number of these uppermost cells is probably not yet prepared to function as metestrus cells and are therefore sloughed off as well. During metestrus compact cell masses stick in the vaginal furrows. Epithelial surface cells are highly irregular and bulging with their microvilli covered surfaces in the vaginal lumen. This study represents the first comprehensive description of alterations on the surface ultrastructure of a marsupial vagina during the estrous cycle, demonstrating considerable differences in comparison to many eutherians.
Progressive Bilateral Sensorineural Hearing Loss Induced by an Antithyroid Drug
Authors: Sano Masaki , Kitahara Nobuo , Kunikata Ryutarou
Published: December 2004

We report a patient with antithyroid drug-induced progressive bilateral sensorineural hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA). While antithyroid drugs have been linked to MPO-ANCA-associated small-vessel vasculitis, sensorineural hearing loss rarely was noted. A 36-year-old man treated for hyperthyroidism with propylthiouracil (PTU) developed progressive bilateral sensorineural hearing loss accompanied by fever and arthritis. MPO-ANCA were demonstrated in serum. Distortion product otoacoustic emissions test results suggested dysfunction of outer hair cells of the organ of Corti. Inner ear blood flow impairment from ANCA-associated small-vessel vasculitis presumably caused cochlear dysfunction. PTU withdrawal and high-dose methylprednisolone administration greatly improved hearing on both sides.
Comparison of Intraocular Pressure Measurements with the Digital Tonometer TGDc-01 ‘PRA’ and the Goldmann Applanation Tonometer
Authors: Meyer Michael W. , Gockeln Roland , Hoy Ludwig , Meyer Andrea , Erb Carl
Published: December 2004

Background: To compare intraocular pressure (IOP) measurements obtained with the digital tonometer TGDc-01 ‘PRA’ with those from a Goldmann applanation tonometer (GAT). Methods: The IOP in 176 eyes of 88 healthy volunteers was measured prospectively in a sitting position. One single measurement, generated by the TGDc-01 PRA, was compared with a single reading from the GAT. Results: Mean IOP values were 13.0 ± 3.7 mm Hg for the TGDc-01 PRA (range, 4–22 mm Hg) and 14.9 ± 3.2 mm Hg for the GAT (range, 8–27 mm Hg). The mean difference was 1.9 mm Hg with a standard deviation of 2.77 mm Hg, and this was statistically significant (p < 0.001, paired t test). Conclusions: In comparison to the GAT, the TGDc-01 PRA underestimated IOP on an average of 1.9 mm Hg. Only 50.6% of all measurements were within the ±2 mm Hg difference range. Thus, the TGDc-01 PRA has no high coincidence degree with the GAT. Both methods were not equivalent.
Ultraviolet B-Induced Corneal and Lens Damage in Guinea Pigs on Low-Ascorbic Acid Diet
Authors: Wu Kaili , Kojima Masami , Shui Ying Bo , Sasaki Hiroshi , Sasaki Kazuyuki
Published: December 2004

To evaluate ocular morphological response to ultraviolet B (UV-B) exposure in guinea pigs fed with normal and low-ascorbic acid (ASA) diets, 24 guinea pigs were randomly divided into UVR (normal diet + UV-B), LVC (low-ASA diet + UV-B) and CTL (normal diet, without UV-B) groups. The irradiated animals were exposed to 8.2 J/cm2 of UV-B over 29 weeks. Changes in the cornea and lens were examined using a Scheimpflug camera, specular microscope and histological studies. ASA contents in the plasma, aqueous humor and lens sections were measured by high-performance liquid chromatography. The results showed low contents of ASA in the plasma, aqueous humor and lens sections in LVC. Both irradiated groups displayed corneal epithelial edema, neovascularization in stroma, increase in corneal thickness, decrease in endothelial density, and lens epithelial damage. No significant morphological differences in cornea and lens were found between guinea pigs fed with low-ASA or normal diet.
Five-Year Trial of Deferiprone Chelation Therapy in Thalassaemia major Patients
Authors: Taher A. , Aoun E. , Sharara A.I. , Mourad F. , Gharzuddine W. , Koussa S. , Inati A. , Dhillon A.P. , Hoffbrand A.V.
Published: December 2004

Twelve thalassaemia major patients have been given deferiprone 75 mg/kg body weight daily as iron chelation therapy for 5 years. Their ages ranged from 18 to 34 years (mean 24.2) at the end of the study. Two patients were hepatitis C virus (HCV) mRNA positive and a further 5 were positive for HCV antibody. The mean serum ferritin level fell significantly from 4,302 ± 2,245 µg/l SD at baseline to 3,032 ± 1,155 µg/l at 2 years (p = 0.037) and 2,229 ± 1,070 µg/l (p = 0.007) at 5 years. At the end of the study, liver iron ranged from 3.59 to 23.7 mg/g dry weight (mean 11.9 ± 5.4), 3 patients having levels >15 mg/g. There was no significant change in serum AST levels, but ALT levels fell significantly at 2 years (p = 0.019) and 5 years (p = 0.001). Liver biopsy at the end of the study showed no evidence of hepatic fibrosis caused by deferiprone. Cardiac studies showed no overall change in left ventricular ejection fraction but a significant improvement in isovolumic relaxation time (p = 0.045). We conclude that in this albeit small group of thalassaemia major patients, deferiprone was a safe long-term method of iron chelation. In a minority, higher doses of deferiprone or a combination with desferrioxamine would be needed to lower liver iron below 15 mg/g.
Performing Bone Marrow Harvest on an Outpatient Basis: A Single Center UK Experience
Authors: Aleem Aamer , Lovell Richard , Holder Kathy , Chakarbarti Suparno , James J. , Milligan Donald W.
Published: December 2004

Bone marrow harvest (BMH) has historically been performed on an inpatient basis with a minimum of overnight inpatient stays. We commenced a program of outpatient (day case) BMH in 1999, performing 54 day case BMHs over a 3-year period. Of the total of 54 cases, 51 were known patients with hematological malignancies and 3 were healthy normal donors. Seven were excluded from day case BMH. Five (10.6%) of 47 patients/donors who were accepted for day case BMH required overnight admission. Two developed hypotension requiring intravenous fluid resuscitation. Two had excessive vomiting and 1 a difficult and prolonged harvest and was admitted at the request of the anesthetist. None of the patients admitted required more than overnight admission and 42 (89.4%) were discharged the same evening. In conclusion, day case BMH is safe, cost-effective, and reduces the pressure on inpatient beds.
Primary Salivary Gland Lymphoma: A Clinicopathologic Study of 23 Cases in Taiwan
Authors: Dunn Po , Kuo Tseng-tong , Shih Lee-Yung , Lin Tung-Liang , Wang Po-Nan , Kuo Ming-Chung , Tang Chung-Chih
Published: December 2004

Twenty-three patients with primary salivary gland lymphoma were diagnosed between 1990 and 2001. The sites of involvement were the parotid gland in 13, the submandibular gland in 9 and the minor salivary gland in 1. The sites of lymphoma involvement beyond the salivary glands were the cervical lymph nodes in 7, bone marrow in 3, the axillary lymph nodes in 3, the nasopharynx in 2, the abdominal lymph nodes in 2, the palate, the subconjunctiva, and the spleen in 1 each patient. Histologically, 19 patients had lymphomas of mucosa-associated lymphoid tissue (MALT) with myoepithelial sialadenitis in 13, 3 patients had diffuse large cell lymphomas and 1 had follicular lymphoma. Six patients were in stage I, 4 in II, 1 in III and 12 in IV. Eight of 23 patients (35%) had autoimmune diseases before or after the diagnosis of NHL and all suffered from MALT lymphoma. Four patients with parotid MALT lymphoma had primary or secondary Sjögren’s syndrome. One each patient suffered from hyperthyroidism, systemic lupus erythematosus, membranoproliferative glomerulonephritis and cryoglobulinemia, respectively. All the 6 stage I patients had achieved complete remission (CR) without relapses 17–84 months (median 44 months) after treatment. Excluding a stage IV patient with follicular lymphoma who died at 3.5 months without treatment, CR was achieved in all of the remaining 16 patients. However, a high relapse rate (9/16, 56%) was noted in stage II–IV patients. These patients tended to relapse in the original sites, but achieved CR again after chemotherapy or radiotherapy. One patient with MALT lymphoma developed histologic transformation into diffuse large lymphoma during relapse and died of refractory disease. Overall, only 2 patients succumbed. The overall survival and relapse-free survival rates at 5 years were 94.7 and 51.4%, respectively. Thus, salivary gland lymphoma proved to be an indolent disease.
Severe Autoimmune Thrombocytopenic Purpura during Interferon-α Therapy for Chronic Myelogenous Leukemia
Authors: Arimura Kosei , Arima Naomichi , Ohtsubo Hideo , Matsushita Kakushi , Kukita Toshimasa , Ayukawa Tomoko , Kuroki Tomoaki , Tei Chuwa
Published: December 2004

Interferon (IFN)-α is a leukocyte-derived cytokine and is used to treat several hematopoietic malignancies. The most common adverse effects of IFN-α are flu-like symptoms and usually insignificant. However, adverse effects due to autoimmune mechanisms are often hazardous and irreversible, although their frequency is low. In the present report, we describe a 55-year-old female with chronic myelogenous leukemia who developed severe autoimmune thrombocytopenia during IFN-α therapy. The lowest platelet count was 6 × 109/l with severe hemorrhagic tendency. The present report strongly suggests the clinical importance of autoimmune thrombocytopenia as an adverse effect of IFN-α.
A Study of Pegylated Liposomal Doxorubicin in Platinum-Refractory Epithelial Ovarian Cancer
Authors: Wilailak Sarikapan , Linasmita Vasant
Published: December 2004

Objectives: The purposes of this study were to determine the efficacy of pegylated liposomal doxorubicin (PLD), using a dose of 40 mg/m2 given every 3 weeks, in the treatment of platinum-refractory epithelial ovarian cancer (EOC) and to evaluate the toxicities. Methods: Fourteen patients with platinum-resistant EOC were treated with intravenous PLD 40 mg/m2 every 3 weeks. Tumor responses were assessed every 2–3 cycles by CT scan. Results: All 14 patients were evaluable for toxicity, but only 13 patients were evaluable for response because 1 patient who had grade 3 palmar-plantar erythrodysesthesia (PPE) refused to continue with the treatment. Three partial responses were observed in 13 patients. The overall response rate was 23% (95% confidence interval 10–38%). The median time to response was 2 months, and the median duration of response was 3 months. The median survival of the 13 patients was 14.5 months, and the median progression-free survival was 6 months. In this study, we had only 4 cases of grade 3 toxicity (2 cases of grade 3 leukopenia and 2 cases of grade 3 PPE). All toxicities that occurred were manageable. Conclusion: This is the first report of the use of a slightly modified dose schedule for PLD at a dose of 40 mg/m2 every 3 weeks, which is active in platinum-refractory EOC with manageable toxicities.
Phase I Study of Hyperfractionated Radiation Therapy with Protracted 5-Fluorouracil Infusion in Patients with Locally Advanced Pancreatic Cancer
Authors: Ueno Hideki , Okusaka Takuji , Ikeda Masafumi , Tokuuye Koich
Published: December 2004

Objective: This study investigated the maximum-tolerated dose of hyperfractionated radiation therapy with protracted 5-fluorouracil (5-FU) infusion in patients with locally advanced, unresectable pancreatic cancer. Methods: Five cohorts of patients were scheduled to receive escalating doses of hyperfractionated radiation therapy (range, 45.6–64.8 Gy). All patients received two fractions of 1.2 Gy each (separated by 6 h) per day for 5 days a week, and received protracted 5-FU infusion (200 mg/m2/day) during the radiation course. The maximum-tolerated dose was defined as one dose level below the dose at which more than one third of 3–6 patients experienced dose-limiting toxicity. Results: Twenty-nine patients were enrolled in this study. The most common toxicities were nausea/vomiting and anorexia. Although 1 patient developed bleeding from a gastric ulcer 3 months after the completion of chemoradiotherapy, the maximum-tolerated dose was not reached even at the highest dose level (level 5, 64.8 Gy). The median survival time was 12.2 months and the 1-year survival rate was 55.0%. Conclusion: The toxicity associated with our regimen was tolerable up to dose level 5 (64.8 Gy). We are currently conducting a phase II study of this hyperfractionated radiation therapy with protracted 5-FU infusion at a dose of 64.8 Gy.
The Prognostic Relevance of Fascin Expression in Human Gastric Carcinoma
Authors: Hashimoto Yosuke , Shimada Yutaka , Kawamura Junichiro , Yamasaki Seiji , Imamura Masayuki
Published: December 2004

Objective: Fascin, an actin-bundling protein that is found in membrane ruffles, microspikes, and stress fibers, induces membrane protrusions and increases cell motility in various transformed cells. The expression of fascin in epithelial neoplasms has been described only recently, and its role in gastric cancer is still unknown. Methods: Paraffin sections of gastric carcinoma from 214 patients were immunohistochemically investigated using monoclonal antifascin antibody. Staining more than 5% of tumor cells was recorded as positive immunoreactivity. Results: Overall, fascin immunoreactivity was detected in 54 out of a total of 214 patients (25%). 26 patients were classified as 1+ (5–25% immunoreactive tumor cells) and 28 were 2+ (>25%). In these patients, 7 tumors showed high (>75%) fascin immunoreactivity. Increased immunoreactivity of fascin was sometimes seen at the edge of the tumor. Fascin immunoreactivity was increased according to the extent of primary tumor (p = 0.026). Fascin expression was correlated with age (p = 0.005), serosal invasion (p = 0.013), positive lymph node metastasis (p = 0.006), histopathological grading (p = 0.019), TNM stage (p = 0.003) and recurrence (p = 0.006); however, it was not correlated with distant metastasis (p = 0.108), Lauren’s type (p = 0.205), or R classification (p = 0.056). Among 166 patients with T1, T2, T3 or T4, those with fascin-positive tumors had a significantly poorer prognosis than those with fascin-negative tumors (p = 0.029). Multivariate analysis showed that fascin expression was not an independent poor prognostic factor. Conclusion: Our findings suggest that the immunohistochemical detection of fascin could provide useful information as one of the prognostic factors in gastric cancer patients.
The Significance of Tumor Location for Gamma Knife Treatment of Meningiomas
Authors: Mindermann Thomas , de Rougemont Olivier
Published: December 2004

We conducted this retrospective review to evaluate the influence of tumor location on the outcome of Gamma Knife treatment (GKT) for meningiomas. Patient charts from 1995 to 2001 of the Gamma Knife Center Zurich, Switzerland, were reviewed. Of 81 patients, 23% had parasagittal or convexity meningiomas (PCM), 62% had skull base meningiomas (SBM), and 15% had posterior fossa meningiomas (PFM). Tumor control was achieved in 95% of PCM, 92% of SBM, and 100% of PFM. Neurological deficits were present in 5% of patients with PCM before and following GKT, in 62% of patients with SBM before GKT and in 46% following GKT, and in 17% of patients with PFM before and following GKT. We conclude that tumor location has an influence on tumor control and outcome. Deep and small tumors seem to be associated with better tumor control and less complications. Neurological deficits tend to resolve in deep tumors following GKT.
Nelson’s Syndrome: Complete Remission with Cabergoline but Not with Bromocriptine or Cyproheptadine Treatment
Authors: Casulari Luiz Augusto , Naves Luciana A. , Mello Paulo A. , Pereira Neto Aldo , Papadia Carla
Published: December 2004

A woman affected by Cushing’s disease underwent bilateral adrenalectomy followed by radiotherapy of the hypothalamic-pituitary area when she was 18 years old. Thereafter, she used hydrocortisone acetate replacement therapy (35.5 mg divided into two daily doses). At the age of 26 years, the patient exhibited the clinical signs of the Nelson’s syndrome, i.e. skin and gingival hyperpigmentation accompanied by amenorrhea, and elevated ACTH plasma levels (2,850 pg/ml, normal range 15–80 pg/ml). The magnetic resonance imaging (MRI) analysis of the sellar region evidenced a pituitary macroadenoma, measuring 14 × 13 mm. The patient was initially treated with cyproheptadine hydrochloride (12 mg/day) for 18 months. There was a partial improvement of the symptoms, with a reduction of the ACTH plasma levels to 112 pg/ml, but without any modification of the tumor mass. Due to sleepiness and weight gain, the cyproheptadine treatment was interrupted and substituted by a cabergoline (0.5 mg twice a week) therapy. Soon after cabergoline was applied an improvement of the clinical symptoms and signs was observed such as a regression of the tumor mass and the normalization of the ACTH plasma titers (38 pg/ml). Later, cabergoline was substituted by bromocriptine (7.5 mg/day) and the plasma levels of ACTH increased again (247 pg/ml), and headache and cutaneous hyperpigmentation were recorded. When cabergoline was reintroduced there was a clinical improvement and normalization of ACTH plasma levels (64 pg/ml). The MRI analysis of the sella region demonstrated a complete remission of the pituitary adenoma. The results obtained show for the first time that a long-term treatment with cabergoline also brings about a complete remission of Nelson’s syndrome in the presence of a pituitary macroadenoma.
Effects of Psyllium on Plasma Total and Lipoprotein Cholesterol and Hepatic Cholesterol in Hamsters Fed n–3 PUFA or n–6 PUFA with High Cholesterol Levels
Authors: Liu Young-Chau , Liu Shyun-Yeu , Lin Mei-Huei
Published: December 2004

This study was conducted to determine whether psyllium is known to alter cholesterol metabolism modulate the hypercholesterolemic effect of a high cholesterol, n–3 polyunsaturated fatty acids (PUFA) diet in hamsters. Concentrations of plasma, hepatic total cholesterol and lipoprotein cholesterol were measured in male hamsters fed an n–3 PUFA plus psyllium (8%, wt/wt) diet combined with variable levels of cholesterol (0, 0.05, 0.1%, wt/wt) or a cholesterol-enriched (0.2%, wt/wt) n–3 PUFA or n–6 PUFA diet that contained either 8% methyl cellulose or psyllium for 4 weeks. In the n–3 PUFA-fed hamsters, we have found that psyllium was able to reduce plasma total cholesterol and low density lipoprotein (LDL)-cholesterol significantly when 0.1% cholesterol was added to the diet. In contrast, the effects of psyllium were not seen in the n–3 PUFA-fed hamsters without dietary cholesterol or with 0.05% dietary cholesterol. However, no matter in the presence of psyllium or not, the increase of plasma total cholesterol, very-low-density lipoprotein (VLDL)-cholesterol, LDL-cholesterol and high-density lipoprotein (HDL)-cholesterol levels was depend on the content of dietary cholesterol. Although the cholesterol diet increased the liver total cholesterol level, 80 g psyllium/kg diet resulted in a significantly lower concentration of liver total cholesterol in the cholesterol-fed hamsters. In the second experiment, we have also found that psyllium feeding lowered significantly plasma total cholesterol and VLDL-cholesterol concentrations in hamsters fed n–3 PUFA but not in those fed n–6 PUFA. However, the levels of plasma total cholesterol, VLDL-cholesterol and LDL-cholesterol levels of the (n-6) PUFA-fed hamsters were significantly lower than those in the (n-3) PUFA-fed hamsters in the absence or presence of dietary psyllium. Our data also showed that hamsters fed both high-cholesterol n–3 PUFA and n–6 PUFA diets had a significant decrease in hepatic cholesterol with intake of psyllium. Liver total cholesterol concentrations were significantly lower in n–3 PUFA-fed hamsters compared with the n–6 PUFA-fed groups. Therefore, these data may contribute to understanding the interactive effect of psyllium and cholesterol or the type of fat on plasma and liver cholesterol in hamsters.