Association between ACTH stimulation test results and clinical signs in dogs with hyperadrenocorticism treated with trilostane.

Trilostane is the recommended medical treatment for dogs with hyperadrenocorticicm (HAC). The objective of this study was to investigate the association between ACTH stimulation test (ACTHST) results, and relevant clinical signs, in dogs treated with trilostane. A disease-specific questionnaire was developed, which included the owner's assessment of polydipsia, polyuria, polyphagia, panting, and satisfaction with the treatment, based on a 5-response category rating scale. Forty-nine dogs with HAC were prospectively enrolled. Dogs were grouped according to their recheck appointment (first recheck, 710 days after commencement of treatment or change of trilostane dose; second recheck, 4 weeks after the first recheck; third recheck, performed at 3-6 months intervals once the dog was well controlled). At the recheck appointment, the owner's questionnaire responses were recorded, and an ACTHST was performed, along with urine specific gravity measurement. Linear mixed effects models were used to assess differences among the three recheck time points and to test possible associations between ACTHST results and clinical signs. Significant differences between rechecks were present for stimulated cortisol (first to third recheck, P < 0.001; second to third recheck, P < 0.01), polydipsia (first to second recheck, P = 0.001), polyuria (first to second recheck, P < 0.001; first to third recheck, P = 0.001), and owner satisfaction (first to second recheck, P < 0.001; first to third recheck, P < 0.001). Backward stepwise variable elimination did not identify any significant associations between ACTHST results and clinical signs. Therefore, clinical signs of HAC were not predicted based on the ACTHST results.

[Standards in the use of fiberoptic endoscopic evaluation of swallowing in Germany : A questionnaire survey]. / Standards bei der Anwendung der fiberendoskopischen Schluckuntersuchung in Deutschland : Eine Fragebogenerhebung.

BACKGROUND: The fiberoptic endoscopic evaluation of swallowing (FEES) is considered to be an indispensable instrumental procedure in the management of patients with dysphagia. The aim of the implemented training curriculum is to raise the quality standards and to contribute to an upgrading of the procedure. OBJECTIVE: The study evaluated to what extent a standardized implementation, evaluation and documentation of FEES takes place in Germany after the introduction of the curriculum. MATERIAL AND METHODS: In this study 603 neurological and geriatric hospitals in Germany were interviewed by the use of an online questionnaire regarding structural features and the course of the investigation. RESULTS: A total of 190 institutions completed the survey. Of the institutions 43.31% had only implemented FEES since the publication of the curriculum. The practical application is increasingly carried out by physicians (59%), the clinical reports and cost recommendations are carried out by speech therapists (62% and 83%, respectively). The practical application by speech therapists increases with increasing level of training. Despite orientation towards the standard protocol according to Langmore, there are differences in the implementation of the anatomical physiological examination, the consistencies and foods administered and the scoring of swallowing-relevant parameters. DISCUSSION: The introduction of the curriculum has led to an upgrading of the FEES and to a strengthening of speech therapy as the implementing professional group. At the current state of the art there is a homogeneous course of the examination in essential aspects but it shows a need for further uniformity. The FEES curriculum could be used as a guiding instrument for further standardization.

The p75 neurotrophin receptor augments survival signaling in the striatum of pre-symptomatic Q175(WT/HD) mice.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a constellation of motor, cognitive, and psychiatric features. Striatal medium spiny neurons, one of the most affected populations, are dependent on brain-derived neurotrophic factor (BDNF) anterogradely transported from the cortex for proper function and survival. Recent studies suggest both receptors for BDNF, TrkB and p75 neurotrophin receptor (p75), are improperly regulated in the striata of HD patients and mouse models of HD. While BDNF-TrkB signaling almost exclusively promotes survival and metabolic function, p75 signaling is able to induce survival or apoptosis depending on the available ligand and associated co-receptor. We investigated the role of p75 in the Q175 knock-in mouse model of HD by examining the levels and activation of downstream signaling molecules, and subsequently examining Hdh(+/Q175);p75(-/-) mice to determine if p75 represents a promising therapeutic target. In Hdh(+/Q175);p75(+/+) mice, we observed enhanced survival signaling as evidenced by an increase in phosphorylation and activation of Akt and the p65 subunit of NFκB in the striatum at 5 months of age and an increase in XIAP expression compared to Hdh(+/+);p75(+/+) mice; this increase was lost in Hdh(+/Q175);p75(-/-) mice. Hdh(+/Q175);p75(-/-) mice also showed a decrease in Bcl-XL expression by immunoblotting compared to Hdh(+/Q175);p75(+/+) and Hdh(+/+);p75(+/+) littermates. Consistent with diminished survival signaling, DARPP-32 expression decreased both by immunoblotting and by immunohistochemistry in Hdh(+/Q175);p75(-/-) mice compared to Hdh(+/+);p75(+/+), Hdh(+/Q175);p75(+/+), and Hdh(+/+);p75(-/-) littermates. Additionally, striatal volume declined to a greater extent in Hdh(+/Q175);p75(-/-) when compared to Hdh(+/Q175);p75(+/+) littermates at 12 months, indicating a more aggressive onset of degeneration. These data suggest that p75 signaling plays an early role in augmenting pro-survival signaling in the striatum and that disruption of p75 signaling at a pre-symptomatic age may exacerbate pathologic changes in Hdh(+/Q175) mice.

[Acute haemorrhagic diarrhoea as a presenting sign in a dog with primary hypoadrenocorticism]. / Akuter blutiger Durchfall als Vorstellungsgrund bei einem Hund mit primärem Hypoadrenokortizismus.

A 7-year-old male castrated mixed breed dog was presented because of acute haemorrhagic vomiting and watery haemorrhagic diarrhoea. According to clinical signs, nonspecific clinicopathological abnormalities, normal electrolytes and a rapid improvement with fluid therapy, haemorrhagic gastroenteritis (HGE) was suspected. One month later the dog was represented with weakness and electrolyte changes characteristic for typical hypoadrenocorticism (hyperkalaemia and hyponatraemia) were found. The tentative diagnosis was confirmed using an ACTH stimulation test. This case report highlights that dogs with hypoadrenocorticism may be presented with acute haemorrhagic diarrhoea. Electrolyte changes characteristic for hypoadrenocorticism may not be present in case of gastrointestinal potassium loss because of vomiting and diarrhoea. To rule out hypoadrenocorticism, a basal cortisol measurement should be performed in every dog with acute haemorrhagic diarrhoea of unknown cause.

Comparison of auricular and rectal temperature measurement in normothermic, hypothermic, and hyperthermic dogs.

OBJECTIVE: Measurement of rectal temperature is the most common method and considered gold standard for obtaining body temperature in dogs. So far, no study has been performed comparing agreement between rectal and auricular measurements in a large case series. The purpose of the study was to assess agreement between rectal and auricular temperature measurement in normothermic, hypothermic, and hyperthermic dogs with consideration of different environmental conditions and ear conformations. MATERIALS AND METHODS: Reference values for both methods were established using 62 healthy dogs. Three hundred dogs with various diseases (220 normothermic, 32 hypothermic, 48 hyperthermic) were enrolled in this prospective study. Rectal temperature was compared to auricular temperature and differences in agreement with regard to environmental temperature, relative humidity, and different ear conformations (pendulous versus prick ears) were evaluated using Pearson's correlation coefficient and Bland-Altman analysis. RESULTS: Correlation between rec- tal and auricular temperature was significant (r: 0.892; p  <  0.01). However, Bland-Altman plots showed an inacceptable variation of values (bias: 0.300 °C; limits of agreement: -0.606 to 1.206 °C). This variation was above a maximal clinical tolerance of 0.3 °C, which was established by experts' opinion (n = 16). Relative humidity had a significant influence (p   =   0.001), whereas environmental temperature did not. CONCLUSION: Variation between the two methods of measuring body temperature was clinically unacceptable. CLINICAL RELEVANCE: Although measurement of auricular temperature is fast, simple, and well tolerated, this method provides a clinically unacceptable difference to the rectal measurement.

[Disseminated intravascular coagulopathy in a dog with Angiostrongylus vasorum infection]. / Disseminierte intravasale Koagulopathie bei einem Hund mit Angiostrongylus-vasorum-Infektion.

A 2-year-old female spayed Epagneul-Breton dog was presented with ecchymoses, but an undisturbed general condition. Clinical examination additionally revealed petechia and a haematoma. Travel history included Italy and Denmark. Laboratory abnormalities were moderate thrombocytopenia, prolonged PT, aPTT and TT, and elevated d-dimers. Initial therapy consisted of plasma transfusions, fluids, doxycycline and famotidine administration. Babesiosis, ehrlichiosis, leishmaniosis, dirofilariosis or anaplasmosis could not be confirmed. Abdominal ultrasound was unremarkable, while thoracic radiographs showed a bronchointerstitial pattern. Faecal samples collected over 3 days were positive for Angiostrongylus vasorum after examination using the Baermann lungworm test. The A. vasorum infection was successfully treated with fenbendazole, whereupon thrombocytopenia and prolonged coagulation times were resolved. In regions of low prevalence, an infection with A. vasorum should also be considered as a differential diagnosis in dogs with coagulation abnormalities. Respiratory signs can be absent with this disease. The patient may have acquired the infection abroad or in Germany.

Associations between proteinuria, systemic hypertension and glomerular filtration rate in dogs with renal and non-renal diseases.

Proteinuria and systemic hypertension are well recognised risk factors in chronic renal failure (CRF). They are consequences of renal disease but also lead to a further loss of functional kidney tissue. The objectives of this study were to investigate the associations between proteinuria, systemic hypertension and glomerular filtration rate (GFR) in dogs with naturally occurring renal and non-renal diseases, and to determine whether proteinuria and hypertension were associated with shorter survival times in dogs with CRF. Measurements of exogenous creatinine plasma clearance (ECPC), urine protein:creatinine ratio (UPC), and Doppler sonographic measurements of systolic blood pressure (SBP) were made in 60 dogs with various diseases. There was a weak but significant inverse correlation between UPC and ECPC, a significant inverse correlation between SBP and ECPC and a weak but significant positive correlation between UPC and SBP. Some of the dogs with CRF were proteinuric and almost all were hypertensive. Neoplasia was commonly associated with proteinuria in the dogs with a normal ECPC. CRF was the most common cause leading to hypertension. In the dogs with CRF, hypertension and marked proteinuria were associated with significantly shorter survival times.

Serotonergic pre-treatments block in vitro serotonergic phase shifts of the mouse suprachiasmatic nucleus circadian clock.

The suprachiasmatic nucleus (SCN) contains a circadian clock that maintains its time-generating and phase-modulating capacities in vitro. Previous studies report clear differences in the ability of serotonergic stimuli to phase-shift the SCN clock when applied directly to the SCN either in vivo or in vitro: while mice and rat circadian clocks are readily phase-shifted by serotonin (5-HT) or 5-HT agonists applied in vitro, hamster and mice circadian clocks respond inconsistently to 5-HT agonists injected directly into the SCN in vivo. Here we have investigated one possible explanation for these differences: that the SCN isolated in vitro experiences reduced endogenous 5-HT signaling, which increases clock sensitivity to subsequent 5-HT stimulation. For these experiments we treated mouse SCN brain slices with low concentrations of compounds that increase serotonin signaling: 5-HT, a 5-HT agonist (8-OH-DPAT), the 5-HT precursor, l-tryptophan, or the 5-HT re-uptake inhibitor, fluoxetine. Pretreatment with each of these substances completely blocked subsequent phase-shifts induced by mid-subjective day treatment with either 5-HT or 8-OH-DPAT, while they did not block phase-shifts induced by the adenylate cyclase activator, forskolin. Time-course data on l-tryptophan-induced inhibition are consistent with this treatment inducing receptor internalization, while timing of the recovery from inhibition is consistent with receptor reinsertion. Together these data support the hypothesis that SCN clock sensitivity to serotonergic phase modulation is affected by the amount of prior serotonin signaling present in the SCN, and that this signaling alters the density of surface 5-HT receptors on SCN clock neurons.

[Photodynamic therapy with verteporfin for recurrent choroidal neovascularisation (CNV) following prior argon laser coagulation]. / Photodynamische Therapie mit Verteporfin bei Rezidiven choroidaler Neovaskularisationen (CNV) nach primärer Argonlaserkoagulation.

BACKGROUND: Photodynamic therapy (PDT) with verteporfin has been successfully introduced to treat choroidal neovascularisations (CNV) that have more than 50% classic CNV components due to exudative age-dependent macular degeneration (AMD) and other diagnoses. However, what is still unclear is if patients with recurrent subfoveal CNV who have had prior laser coagulation can also profit from PDT for CNV. METHODS: The course of visual acuity (ETDRS) and the fluorescein angiographic findings were retrospectively analysed after standard PDT of recurrent subfoveal CNV after prior argon laser coagulation of an extrafoveal or juxtafoveal CNV in AMD or other diagnoses. RESULTS: A total of 20 consecutive eyes from 19 AMD patients were evaluated. After 12 months in 14 of the 20 eyes (70%) deterioration in visual acuity of 3 or more ETDRS lines could be avoided and likewise in 7 of 16 eyes (44%) after 24 months. After the 1st year, 5 of the 7 eyes (71%) with recurrent subfoveal CNV after laser coagulation of a myopic, postinflammatory or idiopathic CNV had deterioration of visual acuity of less than three lines or an improvement in visual acuity. CONCLUSIONS: Despite the low number of patients examined, we could see an indication for PDT in recurrent subfoveal CNV after prior argon laser coagulation of extrafoveal or juxtafoveal CNV. When the patient presented with a CNV cause other than AMD, a better prognosis for visual acuity was achieved.

[Photodynamic treatment with verteporfin for patients with idiopathic choroidal neovascularization. Two-year results]. / Photodynamische Therapie mit Verteporfin bei Patienten mit idiopathischer chorioidaler Neovaskularisation. 2-Jahres-Ergebnisse.

BACKGROUND: The aim of this study was the evaluation of safety and effectiveness of photodynamic therapy (PDT) as a treatment option for idiopathic choroidal neovascularization (CNV). METHODS: We performed a retrospective analysis of 11 eyes of 9 patients who were treated with standard PDT. The follow-up period was at least 1 year and included regular standardized ETDRS visual acuity measurement and fluorescein angiography. RESULTS: Eight sub- and three juxtafoveal CNV were treated. The mean follow-up was 23.2 months (12-41 months), the mean change in visual acuity was +2.1 lines (+3 for juxtafoveal and +1.9 for subfoveal localization), and a mean of 1.9 (1-3) treatments were performed. Visual acuity improved > or =2 lines in 6 of 11 eyes (54.5%) and 5 eyes (45.5%) remained stable (+/-1 lines). Alterations of the retinal pigmented epithelium (RPE) with window defects in fluorescein angiography occurred in 7 of 11 eyes (63.6%) but did not alter visual acuity. In 4 of 11 cases (36.4%), we saw recurrences after initially successful therapy, which were retreated successfully with PDT. CONCLUSION: Stabilization or even an improvement of visual acuity in idiopathic CNV is possible with PDT treatment. Side effects such as RPE changes and recurrences are possible, but do not seem to influence visual acuity.

De-epoxidation of violaxanthin after reconstitution into different carotenoid binding sites of light-harvesting complex II.

In higher plants, the de-epoxidation of violaxanthin (Vx) to antheraxanthin and zeaxanthin is required for the pH-dependent dissipation of excess light energy as heat and by that process plays an important role in the protection against photo-oxidative damage. The de-epoxidation reaction was investigated in an in vitro system using reconstituted light-harvesting complex II (LHCII) and a thylakoid raw extract enriched in the enzyme Vx de-epoxidase. Reconstitution of LHCII with varying carotenoids was performed to replace lutein and/or neoxanthin, which are bound to the native complex, by Vx. Recombinant LHCII containing either 2 lutein and 1 Vx or 1.6 Vx and 1.1 neoxanthin or 2.8 Vx per monomer were studied. Vx de-epoxidation was inducible for all complexes after the addition of Vx de-epoxidase but to different extents and with different kinetics in each complex. Analysis of the kinetics indicated that the three possible Vx binding sites have at least two, and perhaps three, specific rate constants for de-epoxidation. In particular, Vx bound to one of the two lutein binding sites of the native complex, most likely L1, was not at all or only at a slow rate convertible to Zx. In reisolated LHCII, newly formed Zx almost stoichiometrically replaced the transformed Vx, indicating that LHCII and Vx de-epoxidase stayed in close contact during the de-epoxidation reactions and that no release of carotenoids occurred.

Outcome in tall stature. Final height and psychological aspects in 220 patients with and without treatment.

UNLABELLED: In 135 women and 85 men who initially presented for tall stature, the outcome in treated (56 women and 33 men; cases) and untreated (controls) was investigated. At the time of height prediction, cases were significantly taller (P < or = 0.03) than the controls, they had higher target heights (P < 0.001) and adult height predictions (P < 0.001) (according to Bailey and Pinneau) compared to the controls. Bone age (according to Greulich and Pyle) and chronological age were well matched in both groups. Final height was measured after cessation of growth at a mean age above 21.5 years. The final height prediction according to Bailey and Pinneau (BP method) overestimated the final height in controls. The mean error of estimation was -0.14 cm (+/- 3.10) in women, and -1.86 cm (+/- 4.37) in men. Age at the time of prediction did not significantly correlate with the degree of the prediction error. Sex hormone therapy comprised a daily oral dose of 7.5 mg conjugated oestrogens in girls (plus 5 mg dydrogesterone for 10 days a month), while boys received 500 mg testosterone enantate, intramuscularly, every 2 weeks. Therapy was well tolerated. The mean corrected effect of height reducing therapy was 3.6 cm (range: 11.9 cm to -3.3 cm) in women and 4.4 cm (range: 14.2 cm to -5.2 cm) in men. Therapy was significantly more effective when started at an earlier chronological (P < 0.01) and bone age (P < 0.01). The residual mean growth, after therapy was stopped, was 1.8 (+/- 1.6) cm in women and 3.1 (+/- 2.3) cm in men. In men, post-treatment growth was inversely correlated to chronological age (P < 0.01) and bone age (P < 0.05) at the end of treatment, while these correlations were not significant in women. Both groups had a higher educational level than the normal population. Treated tall women reported teasing because of tallness more frequently than controls. In tall men, practical issues such as clothing size predominated. Maximum tolerated height in males was 200 cm and in females 180 cm, thus being nearly analogous to the actual professional criteria for treatment recommendation. A positive attitude to treatment was documented in over 90% of treated individuals. CONCLUSIONS: Our results show that the BP method gives acceptable adult height predictions in girls, but less accurate predictions in boys. The treatment with high doses of sex hormones was low effective in both sexes and showed a wide range of response. For success, treatment must be initiated in early puberty and terminated late. The answers to a questionnaire revealed no major psychological or social maladjustment of treated individuals compared to those untreated.

Biological effects of cosmetic talc.

A review of the literature reveals two primary issues: (1) a weak, but not causal, association of hygienic use of cosmetic talc and ovarian cancer; (2) lung changes in animals exposed to talc aerosol concentrations that resulted in lung overload. The evidentiary weight of the most significant of the epidemiological and laboratory studies and their biological significance for human risk assessment are briefly discussed. Publications describing granulomatous lesions attributed to talc on surgical gloves, and consequences of accidental inhalation of baby powder by infants are also reviewed. The literature reviewed does not provide any convincing evidence that pure cosmetic talc, when used as intended, presents a health risk to the human consumer.

States and functions of tyrosine residues in Escherichia coli asparaginase II.

The importance of five tyrosine residues of Escherichia coli asparaginase II (EcA2) for catalysis and protein stability was examined by site-directed mutagenesis, chemical modification of wild-type and variant enzymes, and by thermodynamic studies of protein denaturation. While the tyrosine residue Y25 is directly involved in catalysis, the hydroxyl groups of residues Y181, Y250, Y289 and Y326 are not necessary for EcA2 activity. However, residues Y181 and Y326 are crucial for stabilization of the native EcA2 tetramer. pH titration curves showed that the active-site residue Y25 has a normal pKa while the C-terminal Y326 is unusually acidic. 1H-NMR signals of a peculiar ligand-sensitive tyrosine residue were assigned to Y25. These and other data suggest that a peptide loop (residues 14-27) which shields the active site during catalysis is highly flexible in the free enzyme.

Site-specific mutagenesis of Escherichia coli asparaginase II. None of the three histidine residues is required for catalysis.

Site-specific mutagenesis was used to replace the three histidine residues of Escherichia coli asparaginase II (EcA2) with other amino acids. The following enzyme variants were studied: [H87A]EcA2, [H87L]EcA2, [H87K]EcA2, [H183L]EcA2 and [H197L]EcA2. None of the mutations substantially affected the Km for L-aspartic acid beta-hydroxamate or impaired aspartate binding. The relative activities towards L-Asn, L-Gln, and l-aspartic acid beta-hydroxamate were reduced to the same extent, with residual activities exceeding 10% of the wild-type values. These data do not support a number of previous reports suggesting that histidine residues are essential for catalysis. Spectroscopic characterization of the modified enzymes allowed the unequivocal assignment of the histidine resonances in 1H-NMR spectra of asparaginase II. A histidine signal previously shown to disappear upon aspartate binding is due to His183, not to the highly conserved His87. The fact that [H183L]EcA2 has normal activity but greatly reduced stability in the presence of urea suggests that His183 is important for the stabilization of the native asparaginase tetramer. 1H-NMR and fluorescence spectroscopy indicate that His87 is located in the interior of the protein, possibly adjacent to the active site.

A catalytic role for threonine-12 of E. coli asparaginase II as established by site-directed mutagenesis.

A threonine-12 to alanine mutant of E. coli asparaginase II (EC 3.5.1.1) has less than 0.01% of the activity of wild-type enzyme. Both tertiary and quaternary structure of the enzyme are essentially unaffected by the mutation; thus the activity loss seems to be the result of a direct impairment of catalytic function. As aspartate is still bound by the mutant enzyme, Thr-12 appears not be involved in substrate binding.

Construction of expression systems for Escherichia coli asparaginase II and two-step purification of the recombinant enzyme from periplasmic extracts.

Isoenzyme II of Escherichia coli L-asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1) is among the few enzymes of major therapeutic importance, being used in the treatment of acute lymphoblastic leukemia. We have constructed several inducible expression systems that overproduce asparaginase II from recombinant plasmids. The most efficient of these systems consists of plasmid pTWE1, a derivative of pT7-7, and an ansB- strain of E. coli, CU1783. These cells produce and secrete amounts of asparaginase II that account for 10-15% of the total cellular protein. Most of the active recombinant enzyme can be released from the periplasmic space by a simple osmotic shock procedure. From the resulting material homogeneous asparaginase II was obtained by a two-step procedure. Overall yields of purified asparaginase were 10-15 mg asparaginase II per liter of E. coli culture. The recombinant enzyme appeared identical to conventionally purified preparations.

Lung changes in rats following inhalation exposure to volcanic ash for two years.

Rats were exposed by inhalation to 5 or 50 mg/m3 Mount St. Helens volcanic ash, to 50 mg/m3 quartz (positive controls), or to filtered room air (sham-exposed controls), for 6 hr/day, 5 days/week, for up to 24 months to investigate biological effects of chronic inhalation exposure to volcanic ash under controlled laboratory conditions. Exposure-related lung changes comprised accelerated respiratory frequency; alveolar macrophage accumulation; interstitial reaction; lymphoreticular reaction in peribronchiolar regions and in mediastinal lymph nodes; alveolar proteinosis in the 50- mg/m3 ash- or quartz-exposed groups; increase in fresh lung weights; decreased body weight and increased mortality in the quartz-exposed group; and epidermoid carcinomas especially in the quartz-exposed females and, to a lesser extent, in the 50-mg/m3 ash-exposed females. The observed changes reflect significant dose-response and agent-response relationships.

On talc translocation from the vagina to the oviducts and beyond.

The objective of this study was to investigate whether multiple vaginal depositions of neutron-activated talc in the cynomolgus monkey result in the translocation of this material to the uterus and beyond. Within a 45-day period, six monkeys received 30 applications of 125 mg neutron-activated talc, suspended in 0.3 ml physiological saline solution containing 1% carboxymethyl cellulose as a suspending agent. The suspension was deposited in the posterior vaginal fornix of the sedated monkeys. Two days after the final talc application, the animals were anaesthetized. Abdominal lavage was performed and the lavage fluid collected for gamma-ray analysis. Also collected for gamma-ray analysis were the following tissues/organs: ovaries, oviducts, uterus, and vagina with cervix. Six untreated control monkeys underwent the same procedures. The radioisotopes 46Sc, 60Co, 59Fe and 51Cr in the activated talc served as tracers. Only the samples containing vagina and cervix from the dosed monkeys contained varying quantities of talc. This demonstrates that no measurable quantities of talc, deposited by multiple applications in the vaginal fornix of the cynomolgus monkey, translocated to the uterus or beyond.

Evaluation of physical health effects due to volcanic hazards: the use of experimental systems to estimate the pulmonary toxicity of volcanic ash.

Shortly after Mount St. Helens erupted in 1980, a number of laboratories began to investigate the effects of volcanic ash in a variety of experimental systems in attempts to predict effects that might occult in the lungs of humans exposed to volcanic ash. The published results are remarkably consistent, despite the use of non-uniform ash samples and variability in the experimental approaches used. The data indicate that volcanic ash, even in high concentrations, causes little toxicity to lung cells in vitro and in vivo, as compared with effects of free crystalline silica, which is known to be highly fibrogenic. Volcanic ash does not appear to be entirely inert, however, possibly because of low concentrations of free crystalline silica in the ash. The published experimental studies suggest that inhaled volcanic ash is not likely to be harmful to the lungs of healthy humans, but the potential effects of volcanic ash in patients with pre-existing lung diseases are more difficult to ascertain from these studies.