Clinical outcome of idiopathic juvenile ventricular arrhythmias in 25 dogs.

INTRODUCTION/OBJECTIVES: Juvenile ventricular arrhythmias in the absence of structural heart disease have been characterized in a small number of canine breeds with limited long-term follow up. The objective of this study was to describe the clinical outcome of dogs with JVA presenting to a university teaching hospital. ANIMALS, MATERIALS, METHODS: Twenty five dogs, less than two years old with idiopathic ventricular arrhythmias were retrospectively identified via a medical record search. Young dogs with ventricular arrhythmias were excluded if they had structural heart disease, systemic illness, or an abnormal troponin (if performed). Electrocardiographic and Holter monitor data was evaluated for arrhythmia frequency and complexity at the time of diagnosis and over time. Long-term follow up was achieved through client and primary veterinarian contact. RESULTS: Breeds included German Shepherd (eight), Boxer (four), Great Dane (three), mixed breed (two) and one each of the following: Anatolian Shepherd, French Bulldog, golden retriever, Great Pyrenees, Labrador retriever, Shiloh Shepherd, miniature Poodle and Siberian Husky. The average age at diagnosis was 7.9 months (range, 2-22 months). The overall median survival was 10.96 years (range, 1.75-15.66 years). There was an average reduction in the number of ventricular beats by 86.7 % per year (P value -0.0257) based on Holter data. CONCLUSION: In most cases, idiopathic juvenile ventricular arrhythmias had a favorable long-term prognosis with reduced ectopy over time in this case series. Juvenile ventricular arrhythmias remains a diagnosis of exclusion but can be considered in a broader range of dog breeds than previously described.

Light-emitting diode flashlights as effective and inexpensive light sources for fluorescence microscopy.

Light-emitting diodes (LEDs) are becoming more commonly used as light sources for fluorescence microscopy. We describe the adaptation of a commercially available light-emitting diode flashlight for use as a source for fluorescence excitation. This light source is long-lived, inexpensive and is effective for excitation in the range of 440-600 nm.

Epidermal growth factor receptors in human breast carcinoma cells: a potential selective target for transforming growth factor alpha-Pseudomonas exotoxin 40 fusion protein.

Epidermal growth factor (EGF) receptors are expressed in high levels by some poor prognosis breast tumors. We have examined the cytotoxic effect of the tumor growth factor alpha (TGF alpha)-delta Cys-Pseudomonas exotoxin (PE40) recombinant fusion protein on normal and tumorigenic human breast epithelial cells in vitro and in vivo. The MDA-468, MDA-231, BT-20, and MCF-7ADR estrogen receptor-negative, EGF receptor-rich breast cancer lines were exquisitely sensitive in vitro to TGF alpha-delta Cys-PE40 with a 50% inhibitory concentration of < or = 0.02 nM. The estrogen receptor-positive, low EGF receptor MCF-7, ZR75-1, and T47D cells were less sensitive to the fusion toxin with a 50% inhibitory concentration of > 0.2 nM. The nontumorigenic cell lines 184, 184A1, and 184B5 were relatively resistant to TGF alpha-delta Cys-PE40 despite exhibiting high levels of EGF receptors. Continuous i.p. administration of TGF alpha-delta Cys-PE40 via an osmotic minipump at a dose of 0.4 microgram/g/day over 7 days inhibited MDA-468, MA-231, and BT-20 but not MCF-7 tumor growth in female athymic mice. Host tissue toxicity was not observed with this dose of TGF alpha-delta Cys-PE40. Mixed MDA-468/MCF-7 tumors were established in nude mice after coinoculation of both cell types in estrogen-supplemented animals. EGF receptor immunohistochemistry and immunoblot procedures indicated that TGF alpha-PE40 eliminated the MDA-468 cells while sparing the adjacent MCF-7 cells. By immunoblot, EGF receptors were consistently more abundant in tumor tissue than in adjacent nontumor tissue from the same mastectomy specimen (n = 7). These data support the notion that EGF receptors can be selectively targeted in human breast cancer cells for the delivery of antitumor agents. Further clinical studies with TGF alpha-delta Cys-PE40 and other chimeric toxins using the same cellular target will address this possibility.

Mean transit time measurement by analysis of a single stool after ingestion of multicolored plastic pellets.

Mean transit time (MTT) was measured in 12 females and served as a standard to evaluate the validity of different methods of estimating transit by analysis of a single stool (SST). Each subject consumed three different fiber supplements and a low-fiber control for 14-d periods. On days 4-8 of each period, subjects were given 20 plastic pallets, which varied in color each day. SST was calculated using from two to five sets of colored pellets and different criteria for designation of the stool to be analyzed were compared. Results indicate that the following modifications in the SST method originally proposed by Cummings and Wiggins will result in improved prediction of MTT: 1) Increase the days of dosing from 3 to 6.2) Collect for study the first stool passed 3 h after the last dosing. 3) Include all pellets identified in the selected stool in the SST calculation.

Effect of psyllium gum and wheat bran on spontaneous energy intake.

Energy intake, fecal energy output, and gastrointestinal symptoms were measured in 12 females who consumed either approximately 23 g/d supplementary fiber or a 4 g/d fiber control. Fiber supplements were crackers containing psyllium gum, wheat bran, or a combination of the two fiber sources. After 1 wk on the control cracker, subjects consumed the three high-fiber crackers and the control cracker for 2-wk periods in a balanced design. Gum and combination supplements gave increased bloating and flatulence. Increase in abdominal pain was reported with gum supplement. Mean daily fecal energy was 96 kcal/d with control crackers and was increased by 63 kcal with high-fiber crackers. Gum and combination supplements significantly decreased intake of digestible energy by 153 and 115 kcal/d, respectively. This suppression was not dependent upon fiber intolerance. Wheat bran supplement had no effect on energy intake.

The care of elderly patients by elderly physicians.

To examine the content of care that elderly patients receive from physicians greater than or equal to 65 years of age, data from the 1981 National Ambulatory Medical Care Survey were analyzed. Compared to physicians aged 35 to 54 years, elderly physicians devoted a larger proportion of their practices to the care of elderly patients. In caring for these patients, elderly physicians spent more time per visit than did younger physicians and were more likely to conduct general examinations and provide counseling. In contrast, elderly physicians were less likely to perform mental status or vision examinations. Elderly physicians were also less likely to provide telephone follow-up for those patients greater than or equal to 75 years of age and more likely to discharge patients greater than or equal to 65 years of age without any specific follow-up planned. These data suggest that the content of care for elderly patients may differ substantially depending upon the physician's age.

Oncogenic transformation of mouse BALB/3T3 cells by plutonium-238 alpha particles.

The A31-11 mouse BALB/3T3 cell system was adapted for the study of malignant transformation induced by 5.3 MeV alpha particles from a specially constructed 238Pu source. The biologic effects were compared to those of 220 kVp X rays. The alpha-radiation survival curve showed a D0 of 70 rad and a relative biological effectiveness (RBE) of 3.5 at 50% survival. The transformation frequency increased exponentially with dose in the range examined (25-250 rad); the maximum RBE for the induction of transformation in growing cells was approximately 3. The RBE for alpha transformation in nonproliferating cells, however, appeared to be much higher; the yield of transformants among X-irradiated cells held in the stationary phase of growth for 6 to 220 hr after irradiation declined nearly 50-fold while no decrease occurred in alpha-irradiated cells. This finding supports the hypothesis that carcinogenic damage induced by high LET radiation in mammalian cells is inefficiently repaired compared with X-ray damage, and that the carcinogenic effect of exposures to high LET radiation may be simply cumulative in nature. It further suggests that the effective RBE for alpha radiation in nonproliferating cell populations in vivo may be much higher than one would predict based on measurements in dividing cells.

The effect of X irradiation on the progression of mouse 10T1/2 cells released from density-inhibited cultures.

When mouse C3H 10T1/2 cells were allowed to reach the density-inhibited plateau phase of growth, 0-3% of the cells were in the S phase as determined by pulse-labeling indices and about 90% of cells were in the G1 phase as determined by flow microfluorometry (FMF). Density-inhibited cultures were exposed to moderate doses of X ray: immediately after X irradiation the cultures were trypsinized and the cells were subcultured at low density in fresh medium. FMF profiles and pulse and continuous-labeling indices were studied. It was determined by pulse-labeling indices that the cell population which was released from the plateau-phase cultures remained in the G1 phase longer than the duration of the normal G1 phase in exponentially growing cells. When plateau-phase cultures were irradiated with 400 rad before subculture, the cells moved into the S phase approximately 4 hr later than did nonirradiated cells. Despite the G1/S delay, both irradiated and nonirradiated cell populations showed a similar rate of progression through the S phase. As determined by cumulative labeling indices, the fraction of cells which remained in G1 up to 120 hr post-subculture (G1 block) increased linearly with X-ray doses. There was no measurable X-ray-induced G1 delay or G1 block in cells irradiated after subculture at the G1/S border during semi-synchronous growth.

Comparison of the effects of psyllium and wheat bran on gastrointestinal transit time and stool characteristics.

Gastrointestinal transit time, frequency of defecation, stool weight, and stool consistency were studied in 12 subjects who were each given fiber supplements containing wheat bran, psyllium gum, a combination of wheat bran and psyllium gum, or a low-fiber control for 2 weeks. Gastrointestinal transit time was measured using four different markers: plastic pellets, chromium mordanted bran, cobalt-ethylenediamine-tetraacetic acid, and terbium oxide. The wet weight and dry weight of stools were measured, and a questionnaire accessed subjects' perceptions of the consistency of their stools. Fiber supplementation decreased transit time and increased the daily number of defecations and the wet weight and dry weight of stools. Bran had a greater effect on transit time than psyllium. Psyllium had a greater effect on the amount of water found in the stools and the total stool weight. On the days that stools were passed, 50% of the daily stool ratings were scored as "hard" when subjects received the control supplement. Less than 10% of the ratings were scored as "hard" when subjects received the high-fiber supplements. The type of marker used did not significantly affect the transit time measured.

A heavy particle comparative study. Part II: cell survival versus depth.

Cell-survival measurements with depth of penetration were made for a series of incident doses of proton, helium, carbon, neon, argon, negative pion, neutron, and 60Co photon beams. Cultured human cells (T1) suspended in a gel-containing medium were used, and the measurements were found to be very useful in facilitating the design of ridge filters to produce iso-effects in the region of interest. Heavy charged particle beams (proton, helium, carbon, neon, and negative pion) were found to produce similar cell killing with depth of penetration. Because of saturation effects at higher LET, argon ions were less effective in killing aerated cells at depth, compared with other heavy charged-particle beams. Cell killing at depth in the region of interest, compared with that at the entrance, was not significantly different for single-field exposures when the Bragg peaks were broadened to cover a width of 10 cm. However, when two opposed fields with overlapping peaks were used, a large enhancement in killing was obtained in the peak region.

OER and RBE for negative pion beams of different peak widths.

Experimental data on survival curves for pion because of different peak widths under aerobic and hypoxic conditions are reported. Metabolic depletion of oxygen by the Chinese hamster cells (line V79) was used to obtain hypoxia. The results indicate that the RBE at the beam entrance (plateau) is approximately 1.0. When the Bragg peaks were broadened to widths of 1.3, 7.8, and 10.5 cm (at the 80% dose level), the RBE (50% cell survival) at the peak centres was 1.7, 1.6, and 1.2, respectively. The OER at the entrance was 2.4 compared with about 2.9 for X rays. The OER was independent of the survival level at which it was measured. The OER at the peak centres at widths of 1.3, 7.8, and 10.5 cm was 2.1, 2.4, and 2.2, respectively. These results indicate that, although the RBE at the centre of the 10.5 cm wide peak was significantly lower than at the centres of the 1.3 and 7.8 cm peaks, the OER values are similar for all peak widths used in this study.

A heavy particle comparative study. Part III: OER and RBE.

The results of a comparative study of heavy particles of interest in radiotherapy are reported in four parts. In this Part III, cell-survival measurements under aerobic and hypoxic conditions were made for various heavy particle beams. For heavy charged-particle beams, the measurements were made at the beam entrance (plateau), peak centre (10 cm wide peaks), and distal peak (1 cm from dose fall-off). Chinese hamster cells (V79) were used. Metabolic depletion was used to obtain hypoxia. The results indicate that the differences in RBE between the entrance region and peak are not very large when the Bragg peaks are broadened to 10 cm. The RBE for argon ions remains the same at the entrance and peak centre, and the RBE at the distal side of the Bragg peak is significantly reduced compared to the peak centre and entrance region because of saturation effects at high LET. The OER for protons is not significantly different from that for X rays. The OER for helium ions, carbon ions, and negative pions is larger, for neon ions is similar, and for argon ions is smaller when compared with fast neutrons. The OER values for heavy ions are higher than expected and could be due to a large delta-ray penumbra associated with the energy deposited by energetic heavy ions. The oxygen effect may depend upon energy deposition over distances of the order of nanometers.

Analysis of neutralizing antibodies to Enterovirus 70 and Coxsackievirus A24 variant, levels of immunoglobulins and total protein in tears of patients with acute hemorrhagic conjunctivitis.

Tear samples were collected from 37 residents of the Dominican Republic <5 d post onset (p.o.) of symptoms (mean 1.73±1.17 d p.o.) of acute hemorrhagic conjunctivitis (AHC). Sixty-two percent (23/37) of the patients had bilateral infections. Anti-enterovirus 70 (EV70) tear neutralizing activity (TNA) (10(2->3.5) U/ml) and anti-Coxsackievirus A24 variant (CA24v) TNA (10(<1-3) U/ml), but no anti-poliovirus (PV) TNA was detected. The anti-EV70 TNA in pooled tear samples sedimented in sucrose density gradient fractions that corresponded to 19-7S serum anti-PV immunoglobulin (1g). Anti-CA24v TNA sedimented as 7S1g. 1gG levels (mean, 3.13±4.2mg/ml) were higher than 1gA levels (mean, 0.92±0.98 mg/ml) in 21 of 27 tear samples. 1gG levels in tears from six patients with bilateral AHC were associated with total tear protein (p=0.003), but not with the levels of TNA or interferon (IFN). The total protein in AHC tears (5.13±1.72 mg/ml) was two-fold less than the total protein in normal tears (11.2±3.25 mg/ml). 1gA levels increased from 0.31±.3 to 1.34±1.28 mg/ml in tears collected up to 3 d p.o. of AHC. 1gM was not detected (<0.01 mg/ml). EV70 was isolated from the tears of one patient. Taken together, our results suggest that EV70 and CA24v are endemic in the Dominican Republic and that the 1992 epidemic of AHC was due to EV70. The detection of 19S (IgM) and high levels of 7S (IgG) TNA to EV70<1 d p.o. of AHC indicate a rapid ocular immune response to EV70 and suggests that virus-specific TNAs inhibit AHC virus infection.

Analysis of foodstuffs for dietary fiber by the urea enzymatic dialysis method.

Total dietary fiber (TDF) values for cereal grains, fruits, vegetables, processed foods, and purified or semi-purified dietary fiber products were determined by a new method using 8M urea and enzymes (urea enzymatic dialysis, UED, method). The results are compared with the official AOAC procedure. Soluble and insoluble dietary fiber were determined for several of these foodstuffs and compared with the NDF values. Crude protein and ash contamination was usually lower with the UED method compared with the AOAC method, particularly for samples that formed gels during ethanol precipitation. Urea and the heat stable amylase were effective in removing starch even at relatively low temperatures of the assay (50 degrees C). The new assay is relatively economical in use of equipment, enzymes, and reagents. Studies are currently in progress to minimize the assay time for the UED method while further improving its flexibility and robustness. The results of the studies will be discussed.

Relative biological effectiveness and microdosimetry of a mixed energy field of protons up to 200 MeV.

We have studied radiation effects utilizing the new 250 MeV Synchrotron at Loma Linda University Medical Center. In this paper we present the data collected for the survival of Chinese hamster lung (V79) cells, that were irradiated with a beam of mixed energy protons up to 200 MeV. The RBE for protons, when compared to 60Co gamma rays, ranged from a low of 1.2 at the high energy portion of the field to 1.3+ at the low energy portion of the field. These results are consistent with the measured lineal energy (microdosimetric) spectra.