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Biomedical subjects

M K Hoffman

Publications and source records attributed to M K Hoffman.

At least 19 recordsLinked to original sources

Endogenous occurrence of some anabolic steroids in swine matrices.

Following findings of 17beta-19-nortestosterone (150-200 microg kg(-1)) in pigs of unspecified gender imported into the European Union, a study to determine steroid and hormone levels in swine from six age/gender categories (uncastrated 'old' boars, cryptorchids, one intersex, barrows, gilts and sows) was initiated. Indeed, for some hormones there has been a discussion about their being endo- or exogenous. Tissue and urine samples from swine from each of the six categories were obtained in Belgium, France, the Netherlands and the USA. Samples were analysed in three laboratories. Quantitation was obtained for norandrostenedione, 19-nortestosterone and boldenone. The results give a well-documented overview of the status of the presence of these hormones in swine. The data illustrate that uncastrated 'old' boars produce the highest percentage of 'positive' matrices, followed by the cryptorchids. Concentrations in the matrices of the barrows and the gilts are lower. Also, sow matrices contain low amounts of nor-steroids. Furthermore, urine samples from an intersex pig contains a higher concentration of nortestosterone than sows and can therefore be suspected for illegal use of these hormones. Veterinarians taking samples in pig farms for the analysis of hormones need to be aware of the presence and concentrations of these substances in the different categories.

Androstenedione↗

Estrogen therapy in women undergoing coronary artery bypass grafting: effect on surgical complications.

OBJECTIVE: To determine whether estrogen therapy at the time of coronary artery bypass grafting affects postoperative complications. METHODS: Consecutive postmenopausal women who had coronary artery bypass grafting between 1992 and 1997 were identified and their medical records were reviewed. Outcome measures included mortality, perioperative cardiac morbidity, and early and late postoperative complications. RESULTS: Estrogen therapy was noted in 13.9% of 734 women. Those using estrogen replacement were younger (63.9 +/- 0.27 versus 68.8 +/- 0.64 years) and had higher ejection fractions (2.8 +/- 0.11 versus 3.1 +/- 0.04) and fewer vessels bypassed. Mortality rates were 2.9% for estrogen users and 7.4% for nonusers (odds ratio [OR] 0.38; confidence interval [CI] 0.07, 1.21). Perioperative cardiac morbidity rates were 5.8% for estrogen users and 11% for nonusers (OR 0.52; CI 0.23, 1.7). Early complication rates were 0. 98% for estrogen users and 1.11% for nonusers. Late inpatient complications were noted in 6.8% of treated women and 14.8% of those untreated (OR 0.42; CI 0.16, 0.96). Stepwise logistic regression confirmed age, New York Heart Association angina classification, and ejection fraction as significant variables for mortality, perioperative cardiac morbidity, and late complications. Estrogen therapy did not influence mortality, perioperative cardiac morbidity, or early or late complications. CONCLUSION: Age, ejection fraction, and New York Heart Association angina classification predicted mortality, perioperative cardiac morbidity, and late complications. Estrogen therapy at the time of admission for coronary artery bypass grafting did not influence surgical mortality, perioperative cardiac morbidity, or early or late complications.

Aged↗

Predictive value for infection of febrile morbidity after vaginal surgery.

OBJECTIVE: To determine the screening value of febrile morbidity for detecting infections after vaginal surgery. METHODS: A cohort of 431 consecutive women had vaginal surgery at the M. S. Hershey Medical Center from September 1988 through June 1995. Outcomes of febrile morbidity and infection were analyzed. RESULTS: Fifty-four of 431 patients (12.5%) had febrile morbidity. Thirty-five infections (8.1%) were identified, of which only 13 were accompanied by febrile morbidity. Forty-one patients (9.5%) had unexplained fevers. The sensitivity of febrile morbidity for postoperative infection was 40%, specificity was 98%, positive predictive value was 26%, and negative predictive value was 94%. Stepwise logistic regression found blood loss (odds ratio 1.001/mL; confidence interval 1.0001-1.0035), uterine weight (0.987/g; 0.976-0.999), and parity (1.570; 1.146-2.050) as significant independent variables for developing fever. Patient weight (0.984/lb; 0.971-0.998) and type of procedure (2.16; 2.12-6.38) were confirmed as significant independent variables for postsurgical infections. CONCLUSION: Febrile morbidity had limited value as a screening test for postoperative infection, with poor sensitivity and positive predictive value after vaginal surgery.

Female↗

Influence of specialty on pathology resource use in evaluation of cervical dysplasia.

OBJECTIVE: Colposcopy is performed by different providers, including nurse practitioners, family physicians, and gynecologists. The training and experience of these providers vary. The fiscal impact of provider type is unknown. This study evaluates pathology resource use by gynecologists and nongynecologists at the time of colposcopy. METHODS: A retrospective cohort study was performed. Data were collected by review of pathology reports and records of all patients with cervical dysplasia treated with cervical excision by loop electrosurgical excision procedure or cold knife conization at our institution between January 1, 1996, and December 31, 1997. Data were analyzed according to type of provider performing the colposcopy before the cervical excision. RESULTS: Gynecologists obtained a total of 190 biopsy specimens in 127 patients, with a mean number of 1.5 +/- 0.75 per patient and a median of 1. Nongynecologists took a total of 148 biopsy specimens in 44 patients, with a mean of 3.4 +/- 1.14 per patient and a median of 3 (P < .001). These differences persisted irrespective of presenting cytology. Nongynecologists were more likely to do endocervical curettage than gynecologists (95% compared with 82%, respectively, P < .001). Cervical dysplasia was diagnosed equally well, even though fewer biopsies were taken by gynecologists. CONCLUSION: Both groups of providers were equally capable of identifying dysplastic lesions. Despite equivalent diagnostic accuracy, nongynecologists used two to three times more pathology resources. If this pattern of use of resources exists at other clinical sites, patients with cervical dysplasia and payers would be better served by gynecologic rather than nongynecologic care.

Adult↗

Regulatory approaches for controlling pesticide residues in food animals.

Pesticide use is vital to the production of an economical, high-quality food supply throughout the world. The regulatory system in the United States is designed to prevent the entry of unacceptable residues into the food supply. To address the complexities associated with pesticide use, the regulatory apparatus is composed of several federal and numerous state agencies. Based on monitoring results, it appears that most pesticides are being used in the appropriate manner and that thresholds for pesticides, deemed to be adequate to protect human health, are seldom exceeded. With our increasing knowledge of the public health and ecologic threats posed by pesticide residues, our approach to regulating pesticides will continue to evolve.

Animals↗

Arteriovenous malformations of the uterus: an uncommon cause of vaginal bleeding.

Arteriovenous malformations (AVM) are rare entities in gynecology, with only 73 cases reported in the literature. Most commonly they present with vaginal hemorrhage, but other presentations such as congestive heart failure, postmenopausal bleeding, and an asymptomatic mass have been described. These lesions may be congenital or acquired. Acquired lesions are believed to follow trauma or may arise after choriocarcinoma or other gynecologic malignancies. Diagnosis can rapidly be made with color flow Doppler ultrasound or angiography. Additionally, they have been detected using hysteroscopy, hysterosalpingogram, and computerized tomography. Acute management consists of hemodynamic stabilization and possibly placement of a Foley bulb in the uterus or methylergonovine injection. Ultimate treatment depends on the patients desire for fertility. Embolization therapy is variably successful and may allow the preservation of reproductive capacity. To date, five pregnancies after embolization have been reported with varying outcomes. If pregnancy is not desired or embolization fails, hysterectomy remains the treatment of choice.

Adult↗

Evaluation of preoperative cardiac risk index values in patients undergoing vaginal surgery.

OBJECTIVE: Our purpose was to evaluate the Goldman and the New York Heart Association cardiac risk index values in a female surgical population and to evaluate age, hypertension, ischemic heart disease, glucose intolerance, cardiac arrhythmia, and estrogen replacement therapy as risk factors for perioperative cardiac morbidity in older women undergoing major vaginal surgery. STUDY DESIGN: A retrospective analysis was performed of perioperative cardiac morbidity in consecutive patients undergoing elective vaginal surgery between August 1987 and October 1993. RESULTS: Four hundred six patients were entered in the study. Eight patients had perioperative cardiac morbidity. The Goldman cardiac risk index and the New York Heart Association functional classification of heart disease were not significant indicators of perioperative cardiac morbidity in this group of patients. In the postmenopausal subgroup of 168 patients hypertension (p = 0.033) and ischemic heart disease (p = 0.004) were statistically significant risk factors for perioperative cardiac morbidity. Glucose intolerance, cardiac arrhythmia, and estrogen replacement therapy were not significant predictors. CONCLUSION: The Goldman cardiac risk index and the New York Heart Association functional classification of heart disease are of questionable utility in a female surgical population undergoing elective vaginal surgical procedures. Hypertension and ischemic heart disease are risk factors for perioperative cardiac morbidity in a postmenopausal subgroup of these patients.

Age Factors↗

Interleukin-2 may enhance or inhibit antibody production by B cells depending on intracellular cAMP concentrations.

The primary IgM response of murine B lymphocytes against red blood cell-bound antigens can be induced by incubating antigen-reactive B cells either with the lymphokines interleukin-1 (IL-1) and IL-2 together with the nucleoside cAMP, or by the addition of antigen-specific helper T cells. The reactivity of B cells is strongly influenced by the T-cell lymphokine IL-2. IL-2 inhibits the cyclic adenosine 3',5'-phosphate (cAMP)-dependent B-cell response when it is allowed to act on the cells prior to cAMP. On the other hand, if IL-2 acts on B cells together with or after cAMP, it synergizes with the nucleoside and enhances the immune response. A similar effect of IL-2 is observed in the T-cell-mediated activation of B cells. If IL-2 is present before helper T cells interacted with B cells, it inhibits antibody production. The inhibitory IL-2 effect is reversed by the simultaneous addition of exogenous cAMP. The finding supports the hypothesis that Ia ligation by T cells results in B cells in the elevation of cAMP which acts as an important second messenger in B cells. The antagonism between cAMP and IL-2 was also examined in the pre-B-cell line 70Z/3. The nucleoside is highly toxic to 70Z/3 pre-B cells and a majority disintegrates within hours of exposure to the nucleoside. The surviving cells undergo phenotypic differentiation expressing surface Ig kappa chains and major histocompatibility complex (MHC) class II molecules, and increase the expression of IL-2 receptor (R). The phenotypic differentiation requires the presence of IL-1. IL-2 inhibits both of these B-cell responses to cAMP, the IL-1-independent cell death, and the IL-1-dependent phenotypic differentiation.

Animals↗

Correlation between interleukin-1 production and engraftment of transplanted bone marrow stem cells in patients with lethal immunodeficiencies.

Interleukin-1 (IL-1) production by endotoxin-stimulated, cultured monocytes from 19 patients with lethal congenital immune disorders were studied and compared with normal controls. Lipopolysaccharide (LPS) stimulated IL-1 production was normal in three of three patients with Wiskott Aldrich syndrome (WAS), two of three combined immunodeficiency with T-cell predominance (CIDTP) and nine of 13 with severe combined immunodeficiency (SCID). Monocytes deficient in IL-1 production could be restored to normal production after incubation with indomethacin in three of five deficient patients. Monocytes from the other two patients could not be induced to generate IL-1, suggesting either an intrinsic deficiency or an alternate inhibitory mechanism as the basis for the IL-1 deficiency observed. In patients with SCID who were transplanted with HLA-haplotype disparate, T-cell depleted marrow without preparative chemotherapy, deficiency of monocyte IL-1 production was correlated with graft failure. Immune reconstitution was achieved in IL-1 deficient patients only when donor monocytes were also engrafted. We hypothesize that deficiencies of IL-1 production may contribute to the heterogeneous expression of combined immunodeficiencies, and may also restrict the engraftment and functional development of allogeneic lymphoid progenitors from a T-cell depleted marrow graft.

Bone Marrow Transplantation↗

A gas chromatographic/mass spectrometric screening, confirmation, and quantification method for estrogenic compounds.

A method is described for the screening, quantification and confirmation of a variety of estronenic substances in animal tissues. A solid-phase extraction technique combined with a liquid/liquid extraction allows for rapid sample preparation and high throughput for the following compounds in bovine liver, muscle and kidney: diethylstilbestrol, dienestrol, hexestrol, zeranol, taleranol, zearalanone, zearalenone, zearalenol, estradiol and estriol. Gas chromatography/mass spectrometry and selected ion monitoring is used for the determination with detection limits ranging from 50 to 150 ppt.

Animals↗

Inhibition of suppressor-cell activity by cyclophosphamide in patients with malignant melanoma.

Twenty patients with malignant melanoma were treated with cyclophosphamide (100, 300 or 500 mg/m2 i.v.) in pilot studies to determine whether such treatment affected suppressor-cell activity. Delayed hypersensitivity to dinitrochlorobenzene and other recall antigens, the serological response to primary immunization with pneumococcal or influenza virus antigens, and the serological response to melanoma antigens were found to be normal and were not changed by cyclophosphamide (Cy) treatment. In vitro assays for production of antibodies against sheep red blood cell (SRBC) antigens, reactivity in the mixed lymphocyte culture reaction, and induction of suppressor cells by Concanavalin-A (Con-A) yielded abnormal results as a consequence of increased suppressor-cell activity in eleven, three, and nine patients, but no concordance was seen between results with the three assays prior to treatment. After treatment with Cy, the results of these tests became normal in seven, three, and seven of the patients with previously abnormal results, independent of the dose given. Examining all patients as a group, a statistically significant effect was seen after treatment with Cy on days 14 and 21 in the assay for the production of antibodies against SRBC, and days 7, 14, 21, 28, and 35 in the assay for Con-A-induced suppressor cells. The decrease in suppressor-cell activity was largely restricted to patients who showed increased suppressor-cell activity prior to treatment with Cy. Our results suggest that increased suppressor-cell activity in patients with malignant melanoma does not affect immune reactions generally but is selective, and that the anti-suppressor-cell effect of Cy is restricted to reactions with increased suppressor-cell activity to start. Based on these results, attempts at increasing the immune response to melanoma antigen vaccines administered between 7 and 35 days after treatment with Cy seem justified.

Antibody Formation↗

Reversal of Con A-induced suppression by a platelet-derived factor which binds to activated suppressor T cells.

A platelet-derived factor found in serum as well as in platelet releasate prepared either with calcium ionophore or with thrombin was shown to reverse Con A-induced suppression of the plaque forming cell (PFC) response to sheep erythrocytes (SRBC) in vivo in (CB6)F1 mice. In addition, as shown previously, lymphoma cell-induced suppression in SJL mice was similarly reversed. The factor could be injected prior to Con A on the day before SRBC injection, or on the same day as antigen with comparable results. It also enhanced PFC responses in the absence of Con A. Suppressor cell induction by Con A in vivo, as demonstrated by assay on PFC responses of normal spleen cells in vitro, was abrogated by simultaneous injection of the platelet factor. Cells from mouse spleen and lymph node, but not from thymus could absorb the factor from human serum at 4 degrees C. The phenotype of the relevant spleen cells was L3T4-, Ly1-, Ly2+, Thy1+, Ly22+, Qa1+, Qa4+, Qa5+, and Ly6.IE+. These results suggest that this factor binds to activated peripheral T cells of the suppressor cell phenotype.

Animals↗

The effects of tumor necrosis factor on the production of interleukin-1 by macrophages.

We investigated the effect of tumor necrosis factor (TNF) on interleukin-1 (IL-1) production by mouse macrophages. At high doses of TNF, macrophages produced no IL-1 (as judged in the LAF assay) even when exposed to bacterial lipopolysaccharide (LPS), an excellent inducer of IL-1 production. In lower (picogram/ml) doses, TNF caused macrophages to make factors which showed modest activity in the LAF assay and that activity could be blocked by antibody to IL-1. TNF induces in low doses also the production of a factor(s) which synergizes with IL-1 in the LAF assay.

Animals↗

B-cell function in common variable immunodeficiency: suppression of in vitro anti-sheep erythrocytes antibody production by T cells and monocytes.

Peripheral blood mononuclear (PBM) cells from five of 21 patients with common variable immunodeficiency (CVI) stimulated in vitro by antigen produced antibodies normally. In 11 of the 16 non-responders, removal of adherent suppressor cells by Sephadex G-10 or removal of monocytes or OKT8 positive suppressor lymphocytes by other means of separation made antibody responses demonstrable. Cells adherent to the G-10 column had suppressor function in the autologous antigen driven system; the suppressor activity appeared to be due to adherent T cells in some patients and to adherent monocytes in others. The suppressor cell functions in these patients did not correlate significantly with the number of cells positive for monoclonal antibodies OKT8 or Leu-2. Factors suppressing antibody production in this system were found in normal serum but usually not in serum of the patients with CVI studied. Substances in normal serum which enhance antibody production in this system when added late in culture were present in serum of patients with CVI. Any abnormality of interleukin-1 production by monocytes of these patients did not seem relevant to the immunodeficiency.

Adolescent↗

Polyclonal and antigen-specific B-cell responses in patients with common variable immunodeficiency.

Antigen-specific antibody responses were investigated in 32 hypogammaglobulinemic patients with common variable immunodeficiency following in vitro sensitization of their peripheral blood lymphocyte cultures with sheep red blood-cell determinants. Anti-sheep red blood-cell antibody-secreting cells were quantitated in a hemolytic plaque assay. Amplification of T-cell help was achieved with the use of the T-cell mitogen concanavalin A or allogeneic irradiated T cells. Four patients groups, A through D, were identified. Group A was comprised of 10 patients whose cultured lymphocyte readily developed into antibody secreting cells. Cultures of 9 patients (Group B) responded suboptimally, but were enhanced following mitogen activation of autologous or exogenous T cells, and those of 7 patients (Group C) responded only when help was amplified. In 7 patients (Group D), no responses were elicited. On the simultaneous assessment of pokeweed mitogen-driven polyclonal generation of immunoglobulin-secreting cells, only 10 responders, all from groups A and B, were identified. Our observations indicate that the majority of patients with common variable immunodeficiency possesses B cells capable of producing antibody in vitro. The ability of some patients' B cells to respond only in the antigen-specific assay while failing to do so in pokeweed mitogen-stimulated cultures suggests that these two reactions are not identical in their activation pathways.

Adolescent↗

Production of thromboxane A2 by the kidney in glycerol-induced acute renal failure in the rabbit.

The hemodynamic alterations occuring in glycerol induced renal failure are controversial. To date no single humoral substance can fully explain the change in renal resistance observed in this hemodynamic model of acute renal failure. To assess the capacity of the rabbit kidney to produce thromboxane A2, a potent vasoconstrictor, the following experiments were carried out. Rabbits received 14 ml/kg of 50% glycerol subcutaneously 24 hrs before the study. After 24 hrs., the kidneys were removed and perfused ex vivo in superfusion bioassay cascade. Kidneys from rabbits which developed renal failure, as assessed by elevated serum creatinines, released a substance which produced contraction of rabbit aorta (RCS) in response to bradykinin (BK) and angiotensin II. Microsomes prepared from these kidneys when incubated with [14C]-arachidonic acid produced a peak of radioactivity which comigrated with thromboxane B2 on the thin layer chromatography and was inhibited by the thromboxane synthetase inhibitor imidazole. Furthermore, an inverse linear relation was found between the BK dose required to release RCS from perfused kidney and the serum creatinine levels. A direct linear relation was found between the percent of TxB2 produced by renal microsome preparations and the serum creatinine. These studies demonstrate an increased renal capacity of the glycerol-model of acute renal failure to produce TxA2. The production of TxA2 a potent vasoconstrictor should therefore be further evaluated as a potential endogenous mediator of the hemodynamic changes occurring in acute renal failure.

Acute Kidney Injury↗