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Biomedical subjects

J C English

Publications and source records attributed to J C English.

At least 73 records · Page 4Linked to original sources
PubMed1994

Measurement of cell proliferation in the kidneys of Fischer 344 and Sprague-Dawley rats after gavage administration of hydroquinone.

Oral administration of hydroquinone (HQ) over 2 years to male Fischer 344 (F344) rats results in a dose-related nephropathy and an increase in the incidence of renal tubule adenomas. Female F344 rats, B6C3F1 mice, and Sprague-Dawley (SD) rats are resistant to the chronic renal toxicity of HQ, and nephrotoxicity was not seen in dogs or humans following subchronic exposure. To better characterize the early development of renal toxicity in rats, cell proliferation was quantitated within the proximal (P1, P2, and P3) and distal tubule segments of the kidney in rats given 0, 2.5, 25, or 50 mg/kg HQ by gavage. Male and female F344 rats were treated for 1, 3, or 6 weeks, and male SD rats were treated for 6 weeks. Cell proliferation was quantitated by incorporation of bromodeoxyuridine, detected immunohistochemically, into newly synthesized DNA. At 6 weeks, renal cell proliferation was increased over vehicle-controls in male F344 rats dosed at 50 mg/kg. Significant elevations (p < 0.001) occurred in the P1 segments (87%) and in the P2 segments (50%) but the elevation in the P3 segment (34%) was not statistically significant. Urinalyses revealed increases in the rate of excretion of enzymes indicative of proximal tubular damage. Histopathologic evaluation of the kidneys was consistent with a dose-related tubular degeneration in the male F344 rat. No chemical-related effects were observed in the kidneys of female F344 and male SD rats. These data parallel the findings of sex- and strain-specific kidney adenomas in the 2-year bioassays, and suggest that chemically induced cell proliferation secondary to toxicity may be important in the pathogenesis of benign renal tumors in male F344 rats treated with HQ.

Animals↗
PubMed1994

Calcium overload during reperfusion is accelerated in isolated hypertrophied rat hearts.

In this study, calcium overload during reperfusion and the severity of morphologically evident ischemic myocardial injury were compared in hypertrophied and normal hearts. Hypertrophied hearts isolated from rats where a clip had been placed on the proximal thoracic aorta for 6 weeks were compared to those from sham-operated rats in an isolated state perfused with Krebs-Henseleit buffer containing 3% albumin, 1.2 mM palmitate and 11 mM glucose. The isolated hearts were exposed to global, no-flow, normothermic ischemia following potassium arrest and were reperfused. Following ischemia and reperfusion, left ventricular end diastolic pressure was increased (39 +/- 7 v 13 +/- 2 mmHg, P < 0.05), and percentage recovery of left ventricular systolic function was decreased (34.4 +/- 8.9 v 77.1 +/- 6.3% P < 0.05), in hypertrophied hearts compared to control hearts. Calcium overload during reperfusion was two and one-half times greater in the hypertrophied hearts than in the control hearts and showed significant relationships with recovery of left ventricular systolic function (r = -0.86, P < 0.001) and left ventricular end diastolic pressure (r = 0.78, P < 0.005). Myocardial energy charge did not differ between the two groups at the end of reperfusion. Ischemic myocardial injury was quantitated morphologically by point counting techniques in a comparable series of control and hypertrophied hearts. After ischemia, hearts were either exposed to a monoclonal antimyosin antibody to identify and measure irreversibly injured myocardium by light microscopy or fixed by perfusion with 2.5% glutaraldehyde to quantitate the morphologic changes ultrastructurally. Control and hypertrophied hearts were not significantly different in severity of myocardial injury due to ischemia as assessed morphologically. Thus, the data suggest that calcium overload during reperfusion plays a significant role in post-ischemic left ventricular dysfunction of the hypertrophied heart. The accelerated calcium overload that occurs in the hypertrophied rat heart during reperfusion cannot be explained by differences in severity of myocardial injury during ischemia which indicates that other mechanisms are responsible.

Animals↗
PubMed1994

The use of pharmacokinetics as an interpretive and predictive tool in chemical toxicology testing and risk assessment: a position paper on the appropriate use of pharmacokinetics in chemical toxicology.

It has been recognized for several decades in the pharmaceutical industry that the safety evaluation of pharmacological agents must include pharmacokinetic (PK) studies, which are designed to determine the rate of absorption, distribution, metabolism, and excretion (ADME). In recent years the importance of such ADME studies in toxicology has also become increasingly apparent to the chemical industry. This increased focus has led to testing strategies that can produce ADME/PK data with greater applicability to toxicity testing and risk assessment. An example of such a strategy is the concept of a tiered approach to the conduct of ADME/PK studies (Wilson, A. G. E., Frantz, S. W., and Keifer, L. C. (1994). Environ. Health Perspect., in press). However, in practice, PK data are often viewed as being of limited usefulness and of only ancillary importance to the determination of chemical toxicity. As a consequence, the close integration of PK studies with toxicity-testing protocols is not always practiced within the chemical industry and is thus frequently scheduled independently from toxicity testing. This lack of integration has resulted in the design of subchronic (13-week) and chronic (2-year) toxicity studies without the benefit of PK information to establish the appropriate dose levels to be used, often because of inappropriate timing. The result is that much of the PK data which have been generated is without a clear consideration of its application to toxicity testing and risk assessment. This position paper is intended to provide recommendations for the appropriate design and interpretation of a PK study, as well as when and how to use PK data in the interpretation of toxicology data. Additional issues discussed in the paper include the design of PK studies to evaluate tissue time-course relationships and chemical persistence, the overall usefulness of PK data to toxicology testing, and the utility of PK as a useful interpretive and predictive tool in toxicology and risk assessment.

Animals↗
PubMed1994

Dermatological manifestations in a tropical training environment: emphasis for the general medical officer.

Cutaneous disease in the tropical training environment will be of concern for the medical officer assigned to ensure the health of soldiers participating in training. A review of all "sick calls" recorded during deployment to the Jungle Operations Training Center at Fort Sherman, Panama showed that 50% of the medical complaints were dermatologically related. This should emphasize the need for medical officers to have significant dermatologic knowledge and appropriate supplies.

Humans↗
PubMed1993

A two-generation reproduction study with hydroquinone in rats.

The effects of hydroquinone (HQ) on reproductive performance and fertility were assessed in a two-generation study with CD Sprague-Dawley rats (one litter per generation). HQ was administered in an aqueous solution by gavage at doses of 0, 15, 50, and 150 mg/kg/day. F0 and F1 parental animals were dosed daily for at least 10 weeks prior to cohabitation, during cohabitation, and until scheduled termination. At all dose levels tested, no adverse effects were observed on feed consumption, survival, or reproductive parameters for the F0 or F1 parental animals. Mild, transient tremors were observed shortly after dosing at 150 mg/kg/day in several F0 and F1 parental animals and in a single F0 male at 50 mg/kg/day. These tremors occurred infrequently and were considered to be due to an acute stimulatory effect of HQ on the nervous system. Body weights for F0 and F1 parental females were similar between all dose groups throughout the study. Body weights for F0 parental males were also comparable to those of control throughout the study. Statistically significant differences in body weights were noted for the F1 parental males in the 50 and 150 mg/kg/day dose groups at several intervals during the premating, mating, and postmating periods. No treatment-related effects on pup weight, sex distribution, or survival were noted for pups of either generation. Upon postmortem examination, no treatment-related gross lesions were observed in either the F0 or F1 parental animals or their weanlings. Histopathologic examination of reproductive tissues and pituitary glands from high-dose F0 and F1 parental animals did not reveal any changes related to treatment with HQ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Eccrine syringofibroadenomatosis: a clinical and histologic study and review of the literature.

A 56-year-old man had an 11-year history of a psoriasiform eruption of the palms, soles, and shins. An examination revealed well-demarcated patches and plaques of erythematous, fissured, and hyperkeratotic skin with focal erosions. There was no clinical evidence of ectodermal dysplasia. On histologic examination these lesions proved to be eccrine hamartomas that consisted of anastomosing cords and strands of cuboidal epithelial cells with well-formed ducts and a fibrovascular mucinous stroma. Eccrine ductal origin was indicated by histopathologic, histochemical, immunopathologic, and electron microscopic evaluation. These multiple palmoplantar eccrine hamartomas, unassociated with ectodermal dysplasia, represent a sporadic hamartomatous condition that is best designated as "eccrine syringofibroadenomatosis."

Adenofibroma↗
PubMed1992

Hydroquinone: a developmental toxicity study in rats.

To determine the potential developmental toxicity of hydroquinone (HQ), pregnant rats (COBS-CD-BR) were given 0, 30, 100, or 300 mg/kg HQ by gavage on the 6th through the 15th days of gestation. Maternal effects included a slight, but significant (p less than or equal to 0.05), reduction in body weight gain and feed consumption for the 300 mg/kg HQ dams. Reproductive indices, i.e., pregnancy rate, numbers of corpora lutea, implantation sites, viable fetuses, and early and late resorptions, fetal sex ratio, pre- and postimplantation losses, and gravid uterine weights, were not affected by treatment with HQ. A slightly reduced (p less than or equal to 0.05) mean fetal body weight seen at the 300 mg/kg dose level was associated with the slightly reduced body weight gain seen for the dams at this dose level. Gross external, internal soft tissue, and skeletal examinations of the fetuses revealed no HQ-related malformations. The incidences of gross external variations (small hematomas) and internal soft tissue variations (dilated renal pelvis, hydronephrosis, and hydroureter) in the HQ-treated litters were not statistically different from the control incidences. Skeletal variations (delayed ossification of membranous skull bones, hyoid bone, thoracic centra 1-3, sacral arches 3 and 4, and bilobed thoracic centra 9-13) were seen with similar frequency in the control and HQ-treated groups. A statistically significant increase in the incidence of total common vertebral variations seen at the 300 mg/kg HQ dose level was not considered toxicologically significant. The incidences of total skeletal variations were not statistically different between the control and the HQ-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1992

A study of developmental toxicity of hydroquinone in the rabbit.

To obtain information on potential developmental toxicity, hydroquinone (HQ) was administered to pregnant New Zealand White rabbits (18 mated per dose group) in aqueous solution (0, 25, 75, or 150 mg HQ/kg/day) by gavage on Gestation Days (GD) 6 to 18. Caesarean sections were performed on GD 30. Doses of 75 and 150 mg/kg/day adversely affected feed consumption and/or body weights of dams during the treatment period. At these doses, however, treatment-related effects were not evident from physical observations, liver and kidney weights, premature delivery incidence, and caesarean sectioning data. The NOEL for maternal toxicity was 25 mg/kg/day. In the 150 mg/kg/day dose group, total incidences of external, visceral, and skeletal findings for fetuses did not differ statistically from controls. Slight, statistically insignificant, increases were found, however, in the incidences of ocular and minor skeletal malformations (micro-ophthalmia, vertebral/rib defects, angulated hyoid arch) on both a per fetus and a per litter basis. Under the conditions of this study, HQ at 150 mg/kg/day produced minimal developmental alterations in the presence of maternal toxicity. The NOEL for developmental toxicity was 75 mg/kg/day.

Animals↗
PubMed1990

Home blood pressure readings in borderline hypertensive patients.

Home blood pressure monitoring can provide valuable information for physicians managing borderline hypertensive patients. This study was conducted to compare office and home blood pressures in 36 borderline hypertensive subjects, and to determine the accuracy of the home monitoring unit used. The patients were very willing to record their home blood pressures for an extended period of time. The home blood pressure monitors were found to be quite accurate, and blood pressures measured at home were significantly lower than readings obtained in the office. In 39% (14 of 36) of the subjects studied, the average home blood pressures were more than 10 mmHg lower than their office readings. These findings support the hypothesis that home blood pressure monitoring can be useful in the management of borderline hypertensive patients.

Adult↗
PubMed1986

Gonococcal dermatitis-arthritis syndrome.

Gonococcal dermatitis-arthritis syndrome should be a diagnostic consideration in an adolescent or a young adult presenting with a skin rash in association with joint pain and swelling. Cultures and/or gram-stained smears should be obtained. Patients usually respond rapidly to antibiotic therapy.

Adult↗
PubMed1981

Toxicokinetics of nickel in rats after intratracheal administration of a soluble and insoluble form.

Ninety day laboratory studies were performed to determine the whole body distribution of two chemical forms of nickel in female Wistar rats. A single injections of 15 microCi of 63Ni, either NiCl2 as a solution or NiO as a suspension, 100 nmoles in each case, was administered intratracheally. Rats were sacrificed at post-exposure intervals of 0.5, 2, and 8 hours, 1, 3, 7, 15, 30, 60 and 90 days, and major organs and tissues were analyzed for 63Ni by liquid scintillation counting technique. The soluble NiCl2 was readily distributed throughout the body, and rapidly cleared from the tissues. The insoluble NiO was distributed slowly to other organs from pulmonary tissues. The rate of decline of 63Ni from various organs in the case of NiO was similar to that of NiCl2, with notable exceptions being the lung and associated lymph nodes. After NiO administration, these organs showed a high retention of nickel after 90 days. Results indicated that Ni in soluble form was rapidly absorbed from the site of deposition following pulmonary exposure, whereas, Ni in its oxide or insoluble form was retained in lungs and related lymphatics for a considerable period. The amount of Ni in other organs following NiO exposure, though initially low in all tissues, declined in a fashion similar to organs following NiCl2 exposure. This suggests that NiO was possibly converted to a soluble form of Ni before it was translocated from lungs to other organs, and that low environmental levels of insoluble forms of nickel, which persist in the lung and lymph nodes, do have the potential for assimilation in these tissues.

Air Pollutants↗
PubMedDate not supplied

Recurrence of intravenous talc granulomatosis following single lung transplantation.

Advanced pulmonary disease is an unusual consequence of the intravenous injection of oral medications, usually developing over a period of several years. A number of patients with this condition have undergone lung transplantation for respiratory failure. However, a history of drug abuse is often considered to be a contraindication to transplantation in the context of limited donor resources. A patient with pulmonary talc granulomatosis secondary to intravenous methylphenidate injection who underwent successful lung transplantation and subsequently presented with recurrence of the underlying disease in the transplanted lung 18 months after transplantation is reported.

Biopsy↗
PubMedDate not supplied

Relationship of hydroquinone-associated rat renal tumors with spontaneous chronic progressive nephropathy.

Hydroquinone exposure has been reported by the National Toxicology Program (NTP) to produce renal tubule adenomas and to exacerbate spontaneous chronic progressive nephropathy (CPN) in male F344 rats. A mechanism for hydroquinone-related tumorigenesis has not been established, but CPN is known to involve, and hydroquinone produces, enhanced renal tubule cell proliferation. Through an independent review of the renal histopathology from the NTP study, the grade of CPN and the presence of atypical tubule hyperplasia and adenomas was evaluated. Hydroquinone exposure in males at 50 mg/kg, produced a statistically significant increase in the grade of CPN. At 0, 25, and 50 mg/kg, 0/44, 4/49, and 15/51 male rats had either atypical tubule hyperplasias or adenomas; all were within areas of severe or end-stage CPN and were statistically significantly associated with CPN grade. Additionally, there was a dose-related increase in profiles believed to represent new tubule proliferation within areas of advanced CPN, as well as an apparent expansion of these into unusual complex tubule profiles in end-stage kidneys of the high-dose male group. In summary, this histopathological review suggest a mechanism for hydroquinone-related adenoma formation that includes enhancement of the severity of CPN coupled with stimulation of tubule proliferation.

Adenoma↗