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1.
J Pediatr Urol ; 15(2): 178.e1-178.e7, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30611650

ABSTRACT

INTRODUCTION: Recurrent urinary tract infections (UTIs) are common in patients with neurogenic bladder (NGB) performing clean intermittent catheterization (CIC) treated with or without oral antibiotic prophylaxis. OBJECTIVE: The authors aim to determine if daily neomycin-polymyxin or gentamicin bladder instillations reduce the rate of symptomatic UTIs, the need for oral antibiotic prophylaxis, emergency department (ED) visits for UTI, and inpatient hospitalizations for UTI in patients with NGB on CIC. The authors also aim to investigate resistance patterns in urine microorganisms in patients treated with antibiotic bladder instillations. STUDY DESIGN: The authors retrospectively reviewed the records of all-age patients cared for in the pediatric urology clinic with NGB on CIC having symptomatic UTIs and on daily intravesical instillations of neomycin-polymyxin or gentamicin between 2013 and 2017. Symptomatic UTIs were defined as a positive urine culture with greater than 10,000 colony forming units/mL associated with one or more of the following patient complaints: cloudy/foul-smelling urine, fevers, chills, increase in bladder spasms, pain, urinary leakage, or physician decision for antibiotic treatment. Multidrug-resistant organisms were resistant to two or more classes of antibiotics. RESULTS: Fifty-two patients with a median age of 14.5 years and 192 distinct urine cultures were identified. 90.4% and 9.6% of patients received neomycin-polymyxin and gentamicin instillations, respectively. After initiation of intravesical antibiotics, the rate of symptomatic UTIs was reduced by 58% (incidence rate ratio [IRR]: 0.42, 95% confidence interval [CI]: 0.31-0.56; P < 0.001), the rate of ED visits was reduced by 54% (IRR: 0.46, 95% CI: 0.30-0.71; P < 0.001), and the rate of inpatient hospitalizations for UTI was reduced by 39% (IRR: 0.61, 95% CI: 0.37-0.98; P = 0.043). Fewer patients received oral antibiotic prophylaxis after initiation of antibiotic instillations (odds ratio: 0.12, 95% CI: 0.02-0.067; P = 0.016). There was a trend toward a decrease in multidrug resistance and no change in gentamicin resistance in urine microorganisms. DISCUSSION: This study describes a feasible alternative treatment for patients with NGB on CIC who have persistent UTIs despite oral antibiotic prophylaxis, and for some patients, it may suggest a possibility of discontinuing oral prophylaxis. Limitations include a retrospective design with a small cohort of patients and varying dosages of neomycin-polymyxin. CONCLUSIONS: Antibiotic bladder instillations appear to decrease frequency of symptomatic UTIs, ED visits for UTI, inpatient hospitalizations for UTI, and the need for oral antibiotic prophylaxis in patients with NGB on CIC. There was no increase in multidrug resistance or gentamicin resistance in UTI organisms with use of intravesical antibiotic instillation.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Gentamicins/administration & dosage , Neomycin/administration & dosage , Polymyxins/administration & dosage , Urinary Bladder, Neurogenic/complications , Urinary Tract Infections/etiology , Urinary Tract Infections/prevention & control , Administration, Intravesical , Adolescent , Child , Drug Combinations , Drug Resistance, Bacterial , Female , Humans , Intermittent Urethral Catheterization , Male , Retrospective Studies , Urinary Bladder, Neurogenic/therapy , Urinary Tract Infections/microbiology , Young Adult
2.
Ann Entomol Soc Am ; 109(5): 713-723, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27651546

ABSTRACT

Private yards comprise a significant component of urban lands, with managed lawns representing the dominant land cover. Lawns blanket > 163,000 km2 of the United States, and 50% of urban and suburban areas. When not treated with herbicides, lawns have the capacity to support a diversity of spontaneous (e.g., not planted) flowers, with the potential to provide nectar and pollen resources for pollinators such as native bees. In order to determine the extent to which suburban lawns support these important species, we surveyed lawns in 17 suburban yards in Springfield, MA, between May and September 2013 and 2014. Householders participating in the study did not apply chemical pesticides or herbicides to lawns for the duration of the study. We collected 5,331 individual bees, representing 111 species, and 29% of bee species reported for the state. The majority of species were native to North America (94.6%), nested in soil (73%), and solitary (48.6%). Species richness was lower for oligolectic (specialists on a single plant; 9.9%) and parasitic species (12.6%). Abundance percentages for number of individuals were similar. We documented 63 plant species in the lawns, the majority of which were not intentionally planted. The most abundant lawn flowers were dandelion (Taraxacum officinale) and clover (Trifolium sp.). Nearly 30% of the spontaneous plant species growing in the lawns were native to North America. Our study suggests that the spontaneous lawn flowers could be viewed as supplemental floral resources and support pollinators, thereby enhancing the value of urban green spaces.

3.
Eur J Pain ; 16(1): 115-22, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21664158

ABSTRACT

This longitudinal study examined the role of the trait of self-criticism as a moderator of the relationship between the affective and sensory components of pain, and depression. One hundred and sixty-three chronic pain patients treated at a specialty pain clinic completed self-report questionnaires at two time points assessing affective and sensory components of pain, depression, and self-criticism. Hierarchical linear regression analysis revealed a significant 3-way interaction between self-criticism, affective pain and gender, whereby women with high affective pain and high self-criticism demonstrated elevated levels of depression. Our findings are the first to show within a broad, comprehensive model, that selfcriticism is activated by the affective, but not sensory component of pain in leading to depressive symptoms, and highlight the need to assess patients' personality as part of an effective treatment plan.


Subject(s)
Affect/physiology , Chronic Pain/complications , Chronic Pain/psychology , Depression/etiology , Depression/psychology , Ego , Adult , Age Factors , Aged , Aged, 80 and over , Data Interpretation, Statistical , Female , Humans , Linear Models , Longitudinal Studies , Male , Middle Aged , Pain Measurement , Personality , Psychiatric Status Rating Scales , Sex Characteristics , Young Adult
5.
Article in English | MEDLINE | ID: mdl-15098199

ABSTRACT

BACKGROUND: VLA-4 (Very late antigen 4, integrin alpha4beta1) plays an important role in cell-cell interactions that are critical for development. Homozygous null knockouts of the alpha4 subunit of VLA-4 or VCAM-1 (cell surface ligand to VLA-4) in mice result in abnormal placental and cardiac development and embryo lethality. Objectives of the current study were to assess and compare the teratogenic potential of three VLA-4 antagonists. METHODS: IVL745, HMR1031, and IVL984 were each evaluated by the subcutaneous route in standard embryo-fetal developmental toxicity studies in rats and rabbits. IVL984 was also evaluated in mice. Fetuses were examined externally, viscerally, and skeletally. RESULTS: IVL745 did not cause significant maternal or fetal effects at doses up to 100 or 250 mg/kg/day in rats or rabbits, respectively. HMR1031 treatment resulted in marked maternal toxicity and slight fetal toxicity at the highest tested doses of 200 and 75 mg/kg/day in rats and rabbits, respectively. HMR1031 embryo-fetal effects consisted of slightly lower body weight and crown-rump length in rats and minor sternebral defects in rabbits. IVL984 treatment resulted in minimal maternal effects at doses up to 40, 15, and 100 mg/kg/day in rats, rabbits, and mice, respectively (excluding abortions in rabbits). However, marked developmental effects were observed at the lowest tested IVL984 doses, 1, 0.2, and 3 mg/kg/day in rats, rabbits, and mice, respectively. IVL984 embryo-fetal effects consisted of increased total post-implantation loss due to early resorptions and high incidences of cardiac malformations and skeletal malformations and/or variations. Notably, spiral septal defects were observed in up to 76% of rat fetuses and up to 58% of rabbit fetuses. CONCLUSIONS: Dramatic differences in teratogenic potential were observed: IVL745 was not teratogenic, HMR1031 caused slight embryo-fetal effects at maternally-toxic doses, and IVL984 was a potent teratogen at doses where direct maternal toxicity was limited to abortions in rabbits. Prominent effects of IVL984 included embryo lethality and cardiac malformations including spiral septal defects in three species.


Subject(s)
Abnormalities, Drug-Induced , Embryo, Mammalian/drug effects , Imidazoles/toxicity , Integrin alpha4beta1/antagonists & inhibitors , Phenylalanine/analogs & derivatives , Phenylalanine/toxicity , Phenylurea Compounds/toxicity , Propionates/toxicity , Animals , Benzene Derivatives , Cell Communication , Dose-Response Relationship, Drug , Drug-Related Side Effects and Adverse Reactions , Embryonic Development/drug effects , Female , Homozygote , Maternal Exposure , Maternal-Fetal Exchange , Mice , Models, Chemical , Pregnancy , Pregnancy, Animal , Rabbits , Rats , Species Specificity , Teratogens/pharmacology
6.
Article in English | MEDLINE | ID: mdl-15098200

ABSTRACT

BACKGROUND: Integrins such as VLA-4 (Very late antigen 4, integrin alpha4beta1) play key roles in cell-cell interactions that are critical for development. Homozygous null knockouts of the VLA-4 alpha4-subunit or VCAM-1 (VLA-4 cell surface ligand) in mice result in failure of the allantois and chorion to fuse leading to interrupted placentation and cardiac development and embryo lethality. Embryo-fetal studies of three VLA-4 antagonists, IVL745, IVL984, and HMR1031 [Crofts et al., Birth Defects Res B 71:55-68 (this issue), 2004] with exposure on gestation days (GD) 6-17 (rat), 6-18 (rabbit) or 6-15 (mouse) showed that only IVL984 treatment resulted in embryo lethality and cardiac defects. Objectives of the current study were to determine the critical period for inducing IVL984-related embryo-fetal effects, and to test the hypothesis that these effects were due to higher embryo drug concentrations. METHODS: IVL984 was administered at 40 mg/kg/day to pregnant rats on GD 4 and 5, GD 6 and 7, GD 8 and 9, GD 10 and 11, or GD 12 and 13. Animals were euthanized on GD 21 and uteri and fetuses were examined. A treatment period of GD 10-12 was selected for subsequent toxicokinetic (TK) studies in which IVL984, HMR1031, or IVL745 was administered to pregnant rats and rabbits. On GD 12, maternal plasma, extra-embryonic tissue (placenta and amniotic fluid), and embryonic tissue were collected and analyzed for drug concentrations. RESULTS: In the IVL984 critical period study in pregnant rats, treatment on GD 10 and 11 resulted in increased post-implantation loss, skeletal variations, and spiral septal defects similar to those observed in standard embryo-fetal development studies with treatment throughout organogenesis. There were no embryo-fetal effects after treatment on GD 4 and 5, GD 6 and 7, or GD 8 and 9. There was a single aorta malformation after treatment on GD 12 and 13. In the TK studies, IVL745, HMR1031, and IVL984 were all detectable in embryonic tissue and there was no evidence for accumulation. Rat and rabbit embryo exposures (AUC or dose-adjusted AUC) on GD 12 could not explain the observed teratology (IVL984

Subject(s)
Abnormalities, Drug-Induced , Embryo, Mammalian/drug effects , Embryonic Development/drug effects , Imidazoles/toxicity , Integrin alpha4beta1/antagonists & inhibitors , Phenylalanine/analogs & derivatives , Phenylalanine/toxicity , Phenylurea Compounds/toxicity , Propionates/toxicity , Teratogens , Animals , Aorta/drug effects , Aorta/embryology , Area Under Curve , Benzene Derivatives , Cell Adhesion , Cell Line , Chorion/drug effects , Dose-Response Relationship, Drug , Drug-Related Side Effects and Adverse Reactions , Female , Heart/drug effects , Humans , Inhibitory Concentration 50 , Integrin alpha4beta1/metabolism , Maternal Exposure , Maternal-Fetal Exchange , Models, Chemical , Pregnancy , Pregnancy, Animal , Protein Binding , Rabbits , Rats , Rats, Sprague-Dawley , Receptors, Very Late Antigen/metabolism , Species Specificity , Time Factors
7.
Pediatr Clin North Am ; 48(6): 1461-88, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11732125

ABSTRACT

The authors do not have all of the data about enuresis, and many children are subject to relapses or failure of treatment. There is no cause for despondency, however. Enuresis is no longer a mystery. Good data exist about the natural history, epidemiology, and etiology of enuresis. In addition, multiple treatment modalities are available to practitioners. This article has sought to review the scientific literature and to relate the authors' experience with enuresis. The authors recommend a treatment program for children with monosymptomatic nocturnal enuresis that includes removal of caffeine from the diet. Enuretic children do not consume enough fluid, and the authors recommend that the daily fluid requirement be divided during the day: 40% in the morning, 40% in the afternoon, and 20% in the evening, with no restriction of fluid. Normalization of small functional bladder capacities may help to cure enuresis and has an effect on the efficacy of other therapies. Treatment of enuretics with antibiotics is effective in children with UTI, bacteriuria, or cystitis cystica. DDAVP has been shown to be effective in the treatment of enuresis, especially in children who have achieved a normal functional bladder capacity. Bladder alarm systems also offer a potential cure of enuresis, are inexpensive, and show a low relapse rate.


Subject(s)
Enuresis , Behavior Therapy , Child , Child Development , Child, Preschool , Deamino Arginine Vasopressin/therapeutic use , Enuresis/diagnosis , Enuresis/epidemiology , Enuresis/etiology , Enuresis/metabolism , Enuresis/physiopathology , Enuresis/psychology , Enuresis/therapy , Humans , Physical Examination , Renal Agents/therapeutic use , Urinary Bladder/physiology , Urodynamics , Vasopressins/metabolism
8.
Pediatr Clin North Am ; 48(6): 1539-57, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11732129

ABSTRACT

The merits of neonatal circumcision continue to be debated hotly. Some argue that circumcision is a "uniquely American medical enigma." Most of the world's male population remains uncircumcised; however, most boys born in the United States continue to undergo neonatal circumcision. Review of existing literature supports that most children who are uncircumcised do well from a medical standpoint and, thus, the question of whether US health care practitioners are subjecting neonates to an unnecessary surgical procedure remains. The medical benefits of circumcision are multiple, but most are small. The clearest medical benefit of circumcision is the relative reduction in the risk for a UTI, especially in early infancy. Although this risk [figure: see text] is real, the absolute numbers are small (risk ranges from 1 in 100 to 1 in 1000), and one investigator has estimated that it may take approximately 80 neonatal circumcisions to prevent one UTI. In the case of a patient with known urologic abnormalities that predispose to UTI, neonatal circumcision has a clearer role in terms of medical benefit to the patient. Most of the other medical benefits of circumcision probably can be realized without circumcision as long as access to clean water and proper penile hygiene are achieved. Proper penile hygiene should all but eliminate the risk for foreskin-related medical problems that will require circumcision. Moreover, proper hygiene and access to clean water has been shown to reduce the rate of development of squamous cell carcinoma of the penis in the uncircumcised population. Proper techniques on the care of the foreskin are illustrated in the American Academy of Pediatrics pamphlet titled "How to care for the uncircumcised penis." Regarding the relationship between STDs and circumcision, patient education and the practice of low-risk sexual behavior make a far greater impact than does routine circumcision in hopes of reducing the spread of HIV and other STDs. Nevertheless, in areas where safe sexual practices are poorly adhered to, circumcision can have a relative protective effect against the transmission of HIV and other STDs. The medical harms of circumcision lie mainly in the 1% acute complication rate and the additional patients who require revision of their initial circumcision for cosmetic or medical reasons. Anecdotally, the authors see far fewer complications in the acute and long-term phase when the circumcision has been performed by someone with expertise and experience with the procedure. Thus, the authors routinely recommend to parents that, if they choose to have their newborns circumcised, they should seek out an experienced practitioner. A negative psychologic and sexual impact of circumcision has been argued, but solid, scientific data are lacking. Special interest groups have argued that perhaps the greatest harm of circumcision is in performing an operation without a clear indication. Many of these groups have claimed that performing a routine neonatal circumcision is akin to performing a surgical procedure without a clear medical benefit, and in an infant, that is akin to surgery without informed consent. Although this is an extreme posture, the clinician can understand the emphasis on trying to provide invasive medical services only when a clear medical benefit is expected, especially when treating an infant or child. Deciding whether or not to circumcise an infant continues to challenge many new parents. Clearly, the procedure provides potential medical benefits and potential risks. It is difficult to say whether the benefits outweigh the risks for all male infants. Further complicating the decision for many American parents is that, in some areas of the United States, there exists an unexplained positive cultural connotation with neonatal circumcision. For these reasons, parents who actively choose to keep their sons uncircumcised need to be encouraged to make this decision forthrightly. Parents who choose to have their children circumcised also should be encouraged to actively seek an experienced practitioner who can afford the child adequate local analgesia.


Subject(s)
Circumcision, Male , Analgesia , Circumcision, Male/adverse effects , Circumcision, Male/history , Circumcision, Male/methods , Circumcision, Male/statistics & numerical data , History, 19th Century , History, 20th Century , History, Ancient , Humans , Infant, Newborn , Male , Penile Diseases/etiology , Penile Neoplasms/prevention & control , Penis/injuries , Sexually Transmitted Diseases/prevention & control , Urinary Tract Infections/prevention & control
9.
J Endourol ; 15(8): 873-80, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11724133

ABSTRACT

BACKGROUND AND PURPOSE: A urodynamic test system of improved accuracy and reliability was developed and implemented for enhancing cystometry. This system integrates known medical information, including the specialized problems of pediatric urodynamics, with the cystometric and imaging data. METHODS: After the requirements for the ideal cystometrogram test unit were established, a system was constructed, calibrated, and implemented in clinical practice. The patient's age, size, and sex are used to produce a patient-specific pressure-volume template for the cystometrogram test. RESULTS: This template showed the minimal and normal bladder capacities and the physiologically safe, equivocal, and dangerous pressure fields coded with symbolic colors. Different time averages of the pressure data were used to show bladder factors such as compliance and instability. The templates with data were presented automatically (therefore objectively) without operator intervention on monitors during testing and as printed copies on completion. CONCLUSIONS: The presentation of data in an easily understood format facilitates effective communication between the urologist, referring physician, and patient. Some of the physiological and statistical problems in pediatric urodynamic testing are efficiently and accurately resolved by this system, resulting in better analysis and diagnostic capabilities.


Subject(s)
Diagnosis, Computer-Assisted , Image Enhancement/methods , Urodynamics , Automation , Child, Preschool , Compliance , Humans , Pressure , Reference Values , Urinary Bladder/physiology , Urinary Bladder/physiopathology
10.
Regul Toxicol Pharmacol ; 33(1): 12-20, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11259175

ABSTRACT

The intraspecies uncertainty factor (UF(HH)=10x) is used in the determination of the reference dose or reference concentration and accounts for the pharmacokinetic and pharmacodynamic heterogeneity within the human population. The Food Quality Protection Act of 1996 mandated the use of an additional uncertainty factor (UF(HC)=10x) to take into account potential pre- and postnatal toxicity and lack of completeness of the data with respect to exposure and toxicity to children. There is no conclusive experimental or theoretical justification to support or refute the magnitude of the UF(HH) and UF(HC) nor any conclusive evidence to suggest that a factor of 100 is needed to account for intrahuman variability. This study presents a new chemical-specific method for estimating the pharmacokinetic (PK) component of the interspecies uncertainty factor (UF(HH-PK) and UF(HC-PK)) for volatile organic compounds (VOCs). The approach utilizes validated physiological-based pharmacokinetic (PBPK) models and simplified physiological-model-based algebraic equations to translate ambient exposure concentration to tissue dose in adults and children the ratio of which is the UF(HH-PK) and UF(HC-PK). The results suggest that: (i) the UF(HH-PK) and UF(HC-PK) are chemical specific; (ii) for the chemicals used in this study there is no significant difference between UF(HH-PK) and UF(HC-PK); (iii) the magnitude of UF(HH-PK) and UF(HC-PK) varies between 0.033 and 2.85 with respect to tissue and blood concentrations; (iv) the body weight, the rate of ventilation, the fraction of cardiac output flowing to the liver, the blood : air partition coefficient, and the hepatic extraction ratio are the only parameters that play a critical role in the variability of tissue and blood doses within species; and (v) the magnitude of the UF(HH-PK) and UF(HC-PK) obtained with the simplified steady-state equations is essentially the same with that obtained with PBPK models. Overall, this study suggests that no adult-children differences in the parent chemical concentrations of the VOCs are likely to be observed during inhalation exposures. The physiological-model-based approaches used in the present study to estimate the UF(HH-PK) and UF(HC-PK) provide a scientific basis for their magnitude. They can replace the currently used empirical default approaches to provide chemical-specific UF(HH-PK) in future risk assessments.


Subject(s)
Models, Biological , Models, Theoretical , Organic Chemicals/adverse effects , Organic Chemicals/pharmacokinetics , Pharmacokinetics , Adolescent , Adult , Age Factors , Animals , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , Probability , Risk Assessment/methods , Volatilization
11.
Infect Immun ; 69(1): 271-80, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11119515

ABSTRACT

Granuloma formation around schistosomal eggs is induced by soluble egg antigens (SEA) and mediated by the activity of CD4(+) Th lymphocytes and their cytokines. Regulation of the inflammatory Th cell response during infection is still insufficiently understood. The hypothesis of this study was that activation-induced cell death (AICD) of CD4(+) T cells is involved in the immune inflammatory response. This study investigated the dynamics of splenic and granuloma CD4(+) Th cell apoptosis and Fas ligand (FasL) expression during the acute and chronic stages of murine schistosomal infection. Enhanced apoptosis of freshly isolated CD4(+) Th lymphocytes commenced after egg deposition and persisted during the peak and modulated phases of granuloma formation. After oviposition, CD4(+), CD8(+), and CD19(+) splenocytes and granuloma cells expressed elevated levels of FasL but FasL expression declined during the downmodulated stage of infection. In culture, SEA induced splenic and granuloma CD4(+) T-cell apoptosis and stimulated expression of FasL on splenic but not granuloma CD4(+) T cells, CD8(+) T cells, and CD19(+) B cells. SEA-stimulated splenocytes and granuloma cells preferentially lysed a Fas-transfected target cell line. Depletion of B cells from SEA-stimulated splenic cultures decreased CD4(+) T cell apoptosis. Coculture of purified splenic B cells with CD4(+) T cells and adoptive transfer of purified B cells indicated that antigen-stimulated B cells can kill CD4(+) Th cells. However, CD4(+) T cells were the dominant mediators of apoptosis in the granuloma. This study indicates that AICD is involved in the apoptosis of CD4(+) T cells during schistosomal infection.


Subject(s)
Antigens, Helminth/immunology , Apoptosis , B-Lymphocytes/physiology , Lymphocyte Activation , Membrane Glycoproteins/physiology , Schistosomiasis mansoni/immunology , T-Lymphocytes, Helper-Inducer/physiology , Animals , Antigens, CD19/analysis , Cytotoxicity, Immunologic , Fas Ligand Protein , Female , Granuloma/immunology , Membrane Glycoproteins/analysis , Mice , Mice, Inbred CBA , Ovum/immunology
13.
Pediatrics ; 104(3): e29, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10469812

ABSTRACT

BACKGROUND: Oral rehydration solutions (ORS) for the treatment of acute diarrhea remain an underutilized therapy in the United States, despite multiple clinical trials confirming their efficacy and safety. Economic barriers to their use have been identified. OBJECTIVE: To determine whether providing ORS to patients at the time of their office visit for acute diarrhea can increase ORS utilization and reduce unscheduled follow-up visits. DESIGN: Randomized, controlled clinical trial. SETTING: Seven health centers of a large health maintenance organization. PARTICIPANTS: Children (N = 479) 0 to 60 months of age with acute diarrhea (at least three watery or loose stools in the previous 24 hours for

Subject(s)
Diarrhea/therapy , Fluid Therapy , Acute Disease , Analysis of Variance , Child, Preschool , Female , Fluid Therapy/economics , Humans , Infant , Infant, Newborn , Logistic Models , Male , Office Visits , Risk Factors , Secondary Prevention , Treatment Outcome
14.
Reprod Toxicol ; 11(6): 799-805, 1997.
Article in English | MEDLINE | ID: mdl-9407590

ABSTRACT

Corticosterone, the predominant circulating adrenal corticosteroid in rodents, was investigated for its effects on reproduction in male Sprague-Dawley rats. Male rats (in groups of 50, 25, and 50) were administered corticosterone at doses of 0, 10, and 25 mg/kg/d, respectively, by subcutaneous injection once daily for 6 weeks; the highest dose was decreased to 20 mg/kg/d after 15 d. During the last 2 weeks of the 6-week treatment period, 25 males per group were paired with untreated females. The remaining 25 males from the 0 and 25/20 mg/kg/d groups were allowed a 6-week recovery period and, during the last 2 weeks of this period, these males were also paired with untreated females. At the end of the treatment period, the males had markedly elevated plasma corticosterone concentrations and decreased weight gain. They also produced fewer copulatory plugs than controls, which may have been secondary to observed adverse effects on the accessory sex organs (decreased weights and microscopic changes in prostate and seminal vesicles). However, no adverse effects on sperm motility, sperm count, or microscopic features of the testes were observed. Serum testosterone concentration of the high-dose males was elevated, but luteinizing hormone was unaffected. The numbers of embryonic implantation sites and live fetuses in females mated to these males were reduced. All of these effects except decreased prostate weights were reversible upon cessation of corticosterone administration. Thus, exogenous administration of corticosterone to male rats produced reversible effects on implant count and litter size of female rats mated to these males. These effects on male rat reproduction may have been secondary to reduced accessory sex organ function, which resulted in diminished secretions and fewer copulatory plugs.


Subject(s)
Anti-Inflammatory Agents/toxicity , Corticosterone/toxicity , Fertility/drug effects , Testis/drug effects , Animals , Body Weight/drug effects , Genitalia, Male/drug effects , Genitalia, Male/pathology , Male , Organ Size , Rats , Rats, Sprague-Dawley , Spermatozoa/cytology , Testis/physiology
15.
Occup Med (Lond) ; 46(3): 186-96, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8695770

ABSTRACT

A physician-based case-control study of non-melanoma skin cancer was conducted to test the hypothesis that employment in the petroleum industry increased the risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or both (BCC+SCC). Other potential risk factors were also investigated. There were 174 cases of BCC, 59 cases of SCC, 72 cases of both and 229 controls completing a self-administered questionnaire. The most important risk factors common to all skin cancer categories were a family history of skin cancer and time spent outdoors. Employment in the petroleum industry showed a slight association with BCC+SCC, but only in the multivariate model. Further study is needed to evaluate whether this association is causal, or due to chance, bias or confounding.


Subject(s)
Carcinoma, Basal Cell/epidemiology , Carcinoma, Squamous Cell/epidemiology , Chemical Industry , Skin Neoplasms/epidemiology , Adult , Case-Control Studies , Humans , Male , Odds Ratio , Risk Factors , Texas/epidemiology
16.
Anaesthesia ; 51(6): 606, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8694231
17.
Mol Immunol ; 32(14-15): 1011-20, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8544850

ABSTRACT

The major histocompatibility (MHC) class I antigens are coordinately expressed in most cells. However, some tumors or virus-infected cells lack expression of one MHC class I antigen, while expression of the other MHC class I antigens is unaffected. We previously described the selective expression of MHC class I antigens on a B-cell lymphoma from SJL/J mice called RCS5. This tumor expresses H-2Ks, but has lost cell surface expression of H-2Ds. To understand the mechanism responsible for the selective loss of H-2Ds on the cell surface, we analysed H-2Ds mRNA and protein in the RCS5 tumor. Here we report that H-2Ds mRNA was expressed in RCS5, but H-2Ds protein was not detected in cell lysates. To determine whether the H-2Ds mRNA from RCS5 was able to direct the synthesis of H-2Ds protein, we performed cDNA cloning, in vitro translation and gene transfer experiments using a cell line related to RCS5 (cRCS-X). Our results indicated that the inhibition of H-2Ds expression in cRCS-X occurred after transcription of a non-defective H-2Ds mRNA. Furthermore, H-2Ds antigen expression was restored in cRCS-X using a retroviral vector to express the recombinant H-2Ds cDNA. These results indicate that the inhibition of H-2Ds expression could be overcome either by out competing an inhibitor that functions in trans or by removing cis-acting regulatory sequences from the endogenous H-2Ds mRNA.


Subject(s)
Gene Expression Regulation, Neoplastic/immunology , H-2 Antigens/genetics , Lymphoma, B-Cell/genetics , Lymphoma, B-Cell/immunology , RNA Processing, Post-Transcriptional/immunology , Amino Acid Sequence , Animals , Base Sequence , Cell Fractionation , Gene Transfer Techniques , Genes, MHC Class I/immunology , Mice , Mice, Inbred Strains , Molecular Sequence Data , Tumor Cells, Cultured
18.
Fundam Appl Toxicol ; 27(2): 270-6, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8529823

ABSTRACT

RG 12915, a selective 5-HT3 antagonist developed for the treatment of emesis and nausea associated with cancer chemotherapy, was administered by gavage to four groups of pregnant rats from Gestation Day 6 to 17 at doses of 0, 1, 10, and 100 mg/kg/day, as part of a Segment II (developmental toxicity) study. The 100 mg/kg/day dose was maternally toxic as indicated by decreased body weight gain and food consumption during the treatment period. A portion of the rats were allowed to deliver and rear their litters and three pups from two litters in the 100 mg/kg/day group were observed to have lens opacities (visible to the naked eye) at weaning. At a later examination, when the offspring were approximately 4 months old, four additional animals from the same two litters had cataracts. A slight growth retardation was also observed postweaning in the offspring of the 100 mg/kg/day group. To confirm the lens findings and more precisely define the no-effect dose, another study was conducted in which pregnant rats were administered daily RG 12915 doses of 0, 10, 30, 60, or 100 mg/kg/day from Gestation Day 6 to 17. There was a dose-related decrement in maternal body weight gain during the treatment period in the 30, 60, and 100 mg/kg/day groups (12, 28, and 47%, respectively) compared to the control group. A treatment-related incidence of nuclear cataract was observed in the offspring of the 60 and 100 mg/kg/day groups (litter incidence 6 and 45%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Benzofurans/toxicity , Bridged Bicyclo Compounds, Heterocyclic/toxicity , Cataract/chemically induced , Prenatal Exposure Delayed Effects , Serotonin Antagonists/toxicity , Animals , Body Weight/drug effects , Cataract/pathology , Female , Lens, Crystalline/pathology , Male , Pregnancy , Rats
19.
Bone Marrow Transplant ; 16(1): 103-9, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7581108

ABSTRACT

We previously found that intracellular ionized calcium ([Ca2+]i) flux responses after anti-CD3 crosslinking of CD3/TCR on T cells from allogeneic and autologous bone marrow transplant (BMT) recipients were impaired, Yamagami et al. J Clin Invest 1990; 86: 1347-1351. In contrast to the earlier study, this study focuses on identifying the T cell subset(s) responsible for the defects and determining if B cell responses are defective in BMT recipients early after BMT. In 37 recipients after anti-CD3 stimulation of PBL, a mean of 25.9% responding T cells was observed. This was significantly lower than the mean of 43.6% responding T cells in PBL from 21 normals (P < 0.001). The proportion of responding T cells in PBL (T PBL) increased in the recipients with time after BMT. By 6 months after BMT, the mean percent of responding T PBL approached the normal range. On the other hand, a mean of 8.1% responding B cells in anti-IgM crosslinked PBL from 24 recipients was not different from the mean of 7.4% responding B cells in anti-IgM crosslinked PBL from 16 normals (P = 0.6). Four color flow cytometry was used to identify subpopulations of lymphocytes. Enriched B cells were tested by gating out CD3+ and CD56+ cells to confirm the results of unfractionated PBL. In 8 recipients, the mean percent responding B cells was 36.6% and was not different from 6 normals (mean = 41.0%).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
B-Lymphocytes/metabolism , Bone Marrow Transplantation/immunology , Calcium/metabolism , Signal Transduction , T-Lymphocytes/metabolism , Adolescent , Adult , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Cell Count , Child , Female , Humans , Ion Transport , Lymphocyte Activation , Male , Middle Aged , T-Lymphocyte Subsets , T-Lymphocytes/immunology
20.
Am J Ind Med ; 27(6): 771-82, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7645572

ABSTRACT

The effectiveness of a program of scheduled bright light and dark to alter the circadian pacemakers of rotating shiftworkers were evaluated. Thirteen industrial workers were exposed to scheduled bright light of 6,000-12,000 lux on at least half of their 12-hr night shifts for 3 months, as well as ambient light of 1,200-1,500 lux. All 10 workers evaluated with urinary melatonin levels had morning melatonin suppression on the night shift, and 50% had a statistically significant circadian change. Although a few significant changes were noted concerning reported sleep and alertness, most findings concerning self-perceived alertness and performance at work, and sleep patterns were mixed and inconsistent. The major complaint was increased difficulty adjusting to being off work after the night shift during the light phase. The alteration in urinary melatonin levels is the first objective demonstration that the bright light technology can alter the circadian pacemakers of workers in an industrial setting. At this worksite, a number of interventions to lessen the effects of rotating shiftwork are being evaluated. Criteria are proposed that should be considered in evaluating a worksite for the use of bright light technology.


Subject(s)
Circadian Rhythm/physiology , Lighting , Personnel Staffing and Scheduling , Work Schedule Tolerance , Adult , Analysis of Variance , Attention , Bias , Cross-Over Studies , Efficiency , Female , Humans , Male , Melatonin/urine , Middle Aged , Sleep/physiology , Surveys and Questionnaires
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