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Biomedical subjects

D J Hoffman

Publications and source records attributed to D J Hoffman.

At least 73 records · Page 4Linked to original sources
PubMed1991

Developmental toxicity of diphenyl ether herbicides in nestling American kestrels.

Beginning the day after hatching, American kestrel (Falco sparverius) nestlings were orally dosed for 10 consecutive days with 5 microliters/g of corn oil (controls) or one of the diphenyl ether herbicides (nitrofen, bifenox, or oxyfluorfen) at concentrations of 10, 50, 250, or 500 mg/kg in corn oil. At 500 mg/kg, nitrofen resulted in complete nestling mortality, bifenox in high (66%) mortality, and oxyfluorfen in no mortality. Nitrofen at 250 mg/kg reduced nestling growth as reflected by decreased body weight, crown-rump length, and bone lengths including humerus, radius-ulna, femur, and tibiotarsus. Bifenox at 250 mg/kg had less effect on growth than nitrofen, but crown-rump, humerus, radius-ulna, and femur were significantly shorter than controls. Liver weight as a percent of body weight increased with 50 and 250 mg/kg nitrofen. Other manifestations of impending hepatotoxicity following nitrofen ingestion included increased hepatic GSH peroxidase activity in all nitrofen-treated groups, and increased plasma enzyme activities for ALT, AST, and LDH-L in the 250-mg/kg group. Bifenox ingestion resulted in increased hepatic GSH peroxidase activity in the 50- and 250-mg/kg groups. Nitrofen exposure also resulted in an increase in total plasma thyroxine (T4) concentration. These findings suggest that altricial nestlings are more sensitive to diphenyl ether herbicides than young or adult birds of precocial species.

Animals↗
PubMed1990

New inhibitors of renin that contain novel phosphostatine Leu-Val replacements.

A novel series of renin inhibitors based on the Phe8-His9-Leu10-Val11 substructure of renin's natural substrate, angiotensinogen, is reported. These inhibitors retain the Phe8-His9 portion of the native substructure and employ novel phosphostatine Leu10-Val11 replacements (LVRs). The phosphostatine LVRs were prepared by condensing a dialkyl phosphonate ester stabilized anion with either N-t-Boc-amino aldehydes or N-tritylamino aldehydes (derived from the corresponding amino acid). Structure-activity relationships at the Leu10 side chain revealed that the LVR derived from L-cyclohexylalanine provided a 130-fold boost in potency over the LVR derived from L-leucine. The dialkyl ester moiety was varied and a loss in potency was incurred when the alkyl ester was chain extended or alpha-branched; dimethyl esters provided optimum potency. The phosphonate moiety was replaced by a half-acid half-ester phosphonate and dimethylphosphinate; both replacements lead to a loss in potency. The more potent inhibitors (IC50 = 20-50 nM) were found to be selective inhibitors for renin over porcine pepsin and bovine cathepsin D (little or no inhibition was observed at 10(-5) M).

Amino Acids↗
PubMed1989

Azido glycols: potent, low molecular weight renin inhibitors containing an unusual post scissile site residue.

Azidomethyl-substituted 1,2- and 1,3-diols were prepared from Boc-cyclohexylalanal and evaluated as transition state analogue renin inhibitors, leading to the development of a small (MW less than 600), nanomolar inhibitor. Remarkable aqueous solubility enhancement followed the incorporation of an N-terminal urea functionality. Evaluation of selected compounds both in vivo and in vitro demonstrated that while transport across the intestine occurred upon id administration, extensive liver extraction resulted in low systemic levels.

Animals↗
PubMed1989

Hepatic glutathione metabolism and lipid peroxidation in response to excess dietary selenomethionine and selenite in mallard ducklings.

Studies were conducted with mallard (Anas platyrhynchos) ducklings to determine the effects of excess dietary selenium (Se) on hepatic glutathione concentration and associated enzymes, and lipid peroxidation. Day-old ducklings were fed 0.1, 10, 20, or 40 ppm Se as seleno-DL-methionine or sodium selenite for 6 wk. Selenium from selenomethionine accumulated in a dose-dependent manner in the liver, resulting in a decrease in the concentration of hepatic-reduced glutathione (GSH) and total hepatic thiols (SH). These effects were accompanied by a dose-dependent increase in the ratio of oxidized glutathione (GSSG) to GSH, and an increase in malondialdehyde concentration as evidence of lipid peroxidation. Hepatic and plasma GSH peroxidase activity was initially elevated at 10 ppm Se as selenomethionine, whereas GSSG reductase activity was elevated at higher dietary concentrations of Se. Selenium from sodium selenite accumulated in the liver to an apparent maximum at 10 ppm in the diet, resulting in an increase in hepatic GSH and GSSG accompanied by a small decrease in total hepatic SH. Sodium selenite resulted in an increase in hepatic GSSG reductase activity at 10 ppm and in plasma GSSG reductase activity at 40 ppm. A small increase in lipid peroxidation occurred at 40 ppm. These findings indicate that excess dietary Se as selenomethionine has a more pronounced effect on hepatic glutathione metabolism and lipid peroxidation in ducklings than does selenite, which may be related to the pattern of accumulation. Effects of Se as selenite appear to be less pronounced in ducklings than reported in laboratory rodents. The effects of selenomethionine, which occurs in vegetation, are of particular interest with respect to the health of wild aquatic birds in seleniferous locations.

Age Factors↗
PubMed1989

Optometry in the multidisciplinary health care setting.

A variety of health care delivery settings and models have been established in the 1980s. The multidisciplinary setting encourages comanagement and continuity of care, provides convenient consultation and communication, and is cost effective. It stimulates learning, helps to consolidate management strategies, and results in improved quality of care. Therefore, the patient and the provider both benefit from this environment. In 1978, the problem-oriented record keeping system (PORS) was implemented in the eye care service of a Boston neighborhood multidisciplinary health center. It facilitated learning, established guidelines for peer review, and improved patient care by assisting the eye care service to communicate patient problems to the other health center services effectively. We review the background of urban multidisciplinary health care settings and the PORS, as well as present several cases in which optometrists participated in patient comanagement with other health care specialists to develop a comprehensive management plan. The benefits of the multidisciplinary approach to both patients and providers are discussed.

Adult↗
PubMed1988

Selenium toxicosis in wild aquatic birds.

Severe gross and microscopic lesions and other changes were found in adult aquatic birds and in embryos from Kesterson Reservoir (a portion of Kesterson National Wildlife Refuge), Merced County, Calif., during 1984. Adult birds from that area were emaciated, had subacute to extensive chronic hepatic lesions, and had excess fluid and fibrin in the peritoneal cavity. Biochemical changes in their livers included elevated glycogen and non-protein-bound sulfhydryl concentrations and glutathione peroxidase activity but lowered protein, total sulfhydryl, and protein-bound sulfhydryl concentrations. Congenital malformations observed grossly in embryos were often multiple and included anophthalmia, microphthalmia, abnormal beaks, amelia, micromelia, ectrodactyly, and hydrocephaly. Mean concentrations of selenium in livers (94.4 ppm, dry weight) and kidneys (96.6 ppm) of birds collected at the Kesterson ponds were about 10 times those found at a nearby control area (8.3 and 12.2 ppm). We conclude that selenium present in the agricultural drainage water supplied to the Kesterson ponds accumulated in the food chain of aquatic birds to toxic concentrations and caused the lesion and other changes observed.

Abnormalities, Drug-Induced↗
PubMed1988

Embryotoxic and teratogenic effects of selenium in the diet of mallards.

Mallards (Anas platyrhynchos) were fed a control diet, diets containing 1, 5, 10, or 25 ppm Se as sodium selenite, or a diet containing 10 ppm Se as seleno-DL-methionine in the first of two experiments. Selenium at 10 ppm as selenomethionine or 25 ppm as sodium selenite caused a 40-44% decrease in the total number of eggs that hatched compared to controls. Selenium at 25 ppm (sodium selenite) resulted in a 19% decrease in mean embryonic weight at 18 d of incubation, accompanied by a 6% decrease in crown-rump length. Ten parts per million Se as selenomethionine was more teratogenic than sodium selenite at 25 ppm. Selenomethionine (10 ppm Se) resulted in an incidence of 13.1% malformations that were often multiple, whereas sodium selenite (10 and 25 ppm Se) resulted in 3.6 and 4.2% malformations. The teratogenicity of selenomethionine was confirmed in a second experiment in which mallards received 1, 2, 4, 8, or 16 ppm Se as selenomethionine, resulting in 0.9, 0.5, 1.4, 6.8, and 67.9% malformations, respectively. These malformations included hydrocephaly, microphthalmia, lower bill defects, and foot defects with ectrodactyly. Both forms of selenium increased the incidence of edema and stunted embryonic growth. Selenomethionine (10 ppm Se) resulted in a significant increase of approximately 40% in plasma glutathione peroxidase activity and a 70% increase in sorbitol dehydrogenase activity (indicative of hepatotoxicity) in hatchlings. Sodium selenite (25 ppm Se) resulted in fourfold elevation in plasma uric acid concentration, indicative of renal alteration. Selenomethionine accumulated much better in eggs than did sodium selenite. These findings indicate that selenomethionine is considerably more teratogenic and generally more embryotoxic than sodium selenite, probably due to higher uptake of selenomethionine.

Animals↗
PubMed1987

Embryotoxicity, teratogenicity, and aryl hydrocarbon hydroxylase activity in Forster's terns on Green Bay, Lake Michigan.

Known reproductive problems, including congenital malformations and poor hatching success, exist for the state endangered Forster's tern (Sterna forsteri) in Green Bay, Wisconsin. Twenty Forster's tern eggs were collected from separate nests at a natural colony with documented reproductive problems, situated at Green Bay, Lake Michigan, and an inland colony at Lake Poygan (control) where reproduction was documented as normal. Eggs from the two locations were placed in the same laboratory incubator and candled throughout incubation. Hatching success of Green Bay eggs was 52% of that for controls. Several early embryonic deaths occurred, but most mortality occurred close to the time of hatching. Liver microsomal aryl hydrocarbon hydroxylase activity was elevated approximately threefold in Green Bay hatchlings compared to controls. Green Bay terns that hatched weighed less than controls, had an increased liver to body weight ratio, and had a shorter femur length. Two Green Bay embryos that failed to hatch had anomalies, one with a crossed beak and one with poor ossification of the foot. One Green Bay hatchling had an abnormally ossified ilium. These effects were observed in eggs where there were measureable levels of aryl hydrocarbon hydroxylase inducers including polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins.

Animals↗
PubMed1987

VA residencies.

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Hospitals, Teaching↗
PubMed1987

Staphyloma and other risk factors in axial myopia.

Posterior staphyloma, associated exclusively with axial myopia, is progressive and often results in visual loss. Five types of primary staphyloma have been described anatomically and in terms of sequelae. Mechanical and physiological factors in axial myopia can lead to potentially sight-threatening abnormalities which affect central or peripheral vision. Some are easily detectable while others require a thorough evaluation of the peripheral retina. This report consists of a review of fundus changes associated with axial myopia, the types of staphyloma, and a case report. Emphasis is placed on identification and management of patients at risk from the sequelae of axial myopia.

Choroid↗
PubMed1986

Association between PCBs and lower embryonic weight in black-crowned night herons in San Francisco Bay.

Reproductive problems, including congenital malformations, reduced hatching success, and decreased survival of hatchlings, have been observed in colonial-nesting water birds at the San Francisco Bay National Wildlife Refuge (SFBNWR). Twenty-four black-crowned night heron (Nycticorax nycticorax) eggs were collected from SFBNWR in 1983. Twelve of these were collected from separate nests when late-stage embryos were pipping, and an additional egg was randomly collected from each nest for organochlorine analysis. Overt anomalies and skeletal defects were not apparent. Embryonic weights (with partially absorbed yolk sacs removed) were 15% lower (p less than 0.05) in SFBNWR embryos compared to control embryos from the Patuxent Wildlife Research Center (PWRC). Crown-rump length and femur length were shorter for SFBNWR embryos. The geometric mean polychlorinated biphenyl (PCB) concentration in SFBNWR eggs was 4.1 ppm wet weight, with a range of 0.8-52.0 ppm. A negative correlation (r = -0.61; p less than 0.05) existed between embryonic weight and log-transformed PCB residues in whole eggs collected from the same nest at SFBNWR, suggesting a possible impact of PCBs on embryonic growth. A correlation with embryonic weight did not occur for DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene] residues. Liver microsomal aryl hydrocarbon hydroxylase activity was neither significantly elevated nor correlated with PCB, DDE, or PCB plus DDE log-transformed residues. It is unknown whether the apparent association between PCBs and lower weight is persistent through hatching.

Animals↗
PubMed1985

Effects of fluoride on screech owl reproduction: teratological evaluation, growth, and blood chemistry in hatchlings.

The effects on reproduction in screech owls (Otus asio) of chronic dietary sodium fluoride administration at 0, 40, and 200 ppm were examined. Fluoride at 40 ppm resulted in a significantly smaller egg volume, while 200 ppm also resulted in lower egg weights and lengths. Day-one hatchlings in the 200 ppm group weighed almost 10% less than controls and had shorter crown-rump lengths. No gross abnormalities were apparent. Skeletal clearing and staining revealed significantly shorter tibiotarsus lengths in the 40 ppm and 200 ppm groups and a shorter radius-ulna length in the 200 ppm group. By 7 days of age, body weights and lengths did not differ from controls, but the tibiotarsus in the 200 ppm group remained shorter. No significant differences were detected in hematocrit, hemoglobin, plasma calcium or alkaline phosphatase. Plasma phosphorus levels were higher in the 40 ppm group than in controls. These results, in combination with the findings of Pattee et al. [25], revealed significant impairment of overall reproduction, suggesting that sodium fluoride could cause slight to moderate reproduction disorders in owls in fluoride-polluted areas.

Abnormalities, Drug-Induced↗
PubMed1985

Biochemical and hematological effects of lead ingestion in nestling American kestrels (Falco sparverius).

One-day old American kestrel (Falco sparverius) nestlings were orally dosed daily with 5 microliters/g of corn oil (controls), 25, 125 or 625 mg/kg of metallic lead in corn oil for 10 days. Forty per cent of the nestlings receiving 625 mg/kg of lead died after 6 days and growth rates were significantly depressed in the two highest lead dosed groups. At 10 days hematocrit values were significantly lower in the two highest lead treated groups, and hemoglobin content and red blood cell delta-aminolevulinic acid dehydratase (ALAD) activity was depressed in all lead treated groups. Plasma creatine phosphokinase decreased in the two highest treatment groups. Brain, liver and kidney ALAD activities, brain RNA to protein ratio and liver protein concentration decreased after lead exposure whereas liver DNA, DNA to RNA ratio and DNA to protein ratio increased. Brain monoamine oxidase and ATPase were not significantly altered. Measurements of the ontogeny of hematological variants and enzymes in normal development, using additional untreated nestlings, revealed decreases in red blood cell ALAD, plasma aspartate amino transferase, lactate dehydrogenase, brain DNA and RNA and liver DNA, whereas hematocrit, hemoglobin, plasma alkaline phosphatase, brain monoamine oxidase, brain ALAD and liver ALAD increased during the first 10 days of posthatching development. Biochemical and hematological alterations were more severe than those reported in adult kestrels or precocial young birds exposed to lead. Alterations may be due in part to delayed development.

Age Factors↗
PubMed1985

Ten years of experience with semen cryopreservation by cancer patients: follow-up and clinical considerations.

Antineoplastic damage to the testicular germinal epithelium with accompanying infertility or subfertility is now a recognized indication for the use of sperm banking. Thus, issues concerning quality of life now compete with questions of survival in decisions made in oncologic settings. In an attempt to learn what concerns patients who use semen preservation facilities, a 10-year retrospective study was undertaken. Registered mail and phone solicitation was used to determine follow-up characteristics of self-referred male cancer patients who voluntarily banked semen at a private facility before they began cancer treatment. The difficulties encountered in conducting follow-up on this group of patients raise questions about sperm banking practices by cancer populations.

Attitude↗