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Biomedical subjects

D Hoffman

Publications and source records attributed to D Hoffman.

At least 109 records · Page 6Linked to original sources

Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural analgesia in obstetrics.

The effects of epidural bupivacaine with and without 1:300,000 epinephrine on uterine activity, progress of labor, fetal heart rate, maternal blood pressure and heart rate, newborn Apgar scores, neonatal acid-base status, and Neurologic and Adaptive Capacity Scoring System (NACS) were compared in 32 parturients during labor and delivery. Patients in group I (n = 16) received 0.5% bupivacaine with 1:300,000 epinephrine and those in group II (n = 16) received 0.5% bupivacaine alone. Addition of epinephrine to bupivacaine had no significant effects on uterine activity, duration of first or second stages of labor, fetal heart rate and variability, or the incidence of abnormal fetal heart rate patterns. Maternal hypotension occurred less frequently in group I than in group II patients (P less than 0.05). Apgar scores, neonatal acid-base status, and the NACS were equally good in the two groups. Duration of analgesia was significantly longer in group I than in group II (186.8 +/- 11.6 vs 85.3 +/- 6.1 (mean +/- SEM) min, P less than 0.001). It is concluded that adding epinephrine to bupivacaine during epidural anesthesia in the normal parturient has no adverse effects on either mother, fetus, neonate, or the progress of labor; and that it significantly prolongs the duration of anesthesia and decreases the incidence of maternal hypotension.

Adult↗

Effects of route of administration and dose on the carcinogenicity of N-nitrosodiethanolamine in the Syrian golden hamster.

N-Nitrosodiethanolamine was assayed for carcinogenicity in Syrian golden hamsters by s.c. injection, topical application, and oral cavity swabbing. Three groups of 30 hamsters each received 27 weekly s.c. injections of either 500, 170, or 58 mg of N-nitrosodiethanolamine per kg in 0.9% NaCl solution. In the group treated with 500 mg/kg, 19 of 30 animals developed nasal cavity tumors, 7 of 30 had tracheal tumors, and 2 of 30 had tumors of the larynx. Among the animals treated with 170 mg/kg, 7 of 29 presented with nasal cavity tumors and 4 of 29 presented with tracheal tumors. In the group treated with 58 mg/kg, only two tracheal tumors were observed. Acetone solutions of N-nitrosodiethanolamine were applied to the shaved backs of three groups of 30 hamsters, each three times weekly for 36 weeks, at doses of 25, 8, or 2.5 mg; the total doses were the same as in the groups treated by s.c. injection. At the 25-mg dose level, 5 of 30 animals developed nasal cavity tumors and 4 of 30 animals had tumors of the trachea. No skin tumors were observed. The incidence of respiratory tract tumors in the groups treated with 8 or 2.5 mg was not significant compared to controls. The oral cavities of 40 hamsters were swabbed three times weekly for 45 weeks with 20 mg of N-nitrosodiethanolamine; the total dose was the same as the highest doses given by s.c. or topical administration. Seventeen of 38 hamsters had nasal cavity tumors, 6 of 38 developed tracheal tumors, and 1 of 38 presented with a tumor of the larynx. No tumors were observed in the oral cavity. The results of this study demonstrate that N-nitrosodiethanolamine is organospecific for the Syrian golden hamster nasal cavity and trachea and that it induces tumors in these sites at doses lower than previously reported.

Administration, Oral↗

Activities of an employer independent Occupational Medicine Clinic, Cook County Hospital, 1979-1981.

In July 1976, Cook County Hospital, a 1,363-bed general public hospital in Chicago, Illinois, established a hospital-funded Occupational Medicine Clinic. A review was made of the clinic records of the 486 new patients evaluated at the clinic from July 1979 to June 1981. Information is presented concerning age, ethnic origin, sex, union representation, referral sources, reason for the referral, number and type of toxic exposure, diagnosis, occupational relationship of the disease, and disposition.

Adolescent↗

Familial thyroid hormone resistance.

Eight patients with thyroid hormone resistance were found in four generations of a kindred containing 19 members. Results of studies in this family are consistent with an autosomal dominant mode of inheritance for this disorder. The affected family members were clinically euthyroid but all had goiters and markedly increased serum thyroid hormone levels: thyroxine (T4) = 21.1 +/- 2.1 microgram/dl; triiodothyronine (T3) = 323 +/- 60 ng/dl; free T4 = 5.4 +/- 0.9 ng/dl; and free T3 = 1,134 +/- 356 pg/dl (mean +/- SD). Serum thyrotropin (TSH) levels were normal or slightly elevated in six patients and responded normally to the administration of thyrotropin-releasing hormone (TRH) and L-triiodothyronine. Two patients who had previously undergone subtotal thyroidectomy had elevated baseline serum TSH levels and exaggerated TSH responses to the administration of TRH suggesting subclinical hypothyroidism despite elevated total and free thyroid hormone levels. The absence of thyrotoxicosis and normal serum TSH levels despite elevated serum free T3 and T4 levels in the untreated members of this family are consistent with resistance of pituitary and peripheral tissues to the actions of thyroid hormones. In addition, the absence of hypothyroidism and normal responsiveness of serum TSH to TRH and L-triiodothyronine administration in untreated family members suggest that the thyroid has compensated for the hormone resistance by increased secretory activity under the control of pituitary TSH secretion.

Adolescent↗

Adrenal steroid inhibition of the vasopressin-neurophysin neurosecretory system to the median eminence of the rat. Differential effects of corticosterone and deoxycorticosterone administration after adrenalectomy.

Neurophysin and vasopressin-containing terminals in the zona externa of the median eminence (ZE) show a large increase in immunoreactive peptide following adrenalectomy which can be prevented by dexamethazone replacement therapy. The present study was undertaken to determine the effectiveness of a glucocorticoid (corticosterone; CS) and a mineralocorticoid (deoxycorticosterone: DOC) in exerting negative feedback on this system. Animals were adrenalectomized and implanted with various sized pellets of either steroid or cholesterol. The amount of neurophysin-immunoreactivity in the ZE 2 weeks after adrenalectomy was estimated on a zero to four rank scale independently by three observers. The data were analyzed by the X2 statistic. Low doses of CS (50 mg) reduced the amount of staining in comparison to cholesterol-replaced animals by approximately 50%. The ZE of animals receiving higher doses (100--200 mg) were identical to those of intact animals. DOC, however, at the 50 or 100 mg level produced only a slight inhibition of the response to adrenalectomy. Larger pellets (150--200 mg) did not result in a level of ZE staining as low as for intact animals. These findings suggest that the vasopressin neurosecretory system to the ZE is regulated by glucocorticoids.

Adrenalectomy↗

Endometrial biopsy using a plastic curette (Mi-Mark).

Using soft (Mi-Mark) and sharp (Novak) curette endometrial biopsies were performed for the purpose of cancer screening and ovulation detection in five and 44 cases, respectively. The new devised plastic curette (Mi-Mark) when compared to the metal curette proved to be equally effective in obtaining an adequate endometrial sample for histologic evaluation. Due to the flexibility of the plastic curette endometrial biopsies were performed atraumatically and with the least amount of pain in most cases.

Biopsy↗

Mutagenicity, tumor-initiating activity, and metabolism of methylphenanthrenes.

The mutagenicity, in vitro metabolism, and tumor-initiating activity of methylphenanthrenes were evaluated. The only monomethyl isomers which were mutagenic toward Salmonella typhimurium were 1- and 9-methylphenanthrenes. Among the disubstituted phenanthrenes assayed for mutagenicity, only 1,4-dimethylphenanthrene was active in the presence of metabolic activation. Studies on the in vitro metabolism of methylphenanthrenes were performed by incubation of the various isomers with the 9000 X g supernatant from Aroclor-treated rat livers. Comparison of mutagenicity with metabolites formed in vitro indicated that inhibition of 9,10-dihydrodiol formation was positively associated with mutagenic activity. Among the metabolites of 1- and 9-methylphenanthrenes, significant mutagenic activity was associated only with the 3,4- and/or 5,6-dihydrodiol. Metabolism to the 1,2- or 7,8-dihydrodiol, the requisite dihydrodiols for formation of "bay-region" dihydrodiol-epoxides, was most significant in the case of 4-methylphenanthrene. None of the isomeric methylphenanthrenes were active when assayed as tumor initiators on mouse skin. In contrast, 1,4-dimethylphenanthrene was found to have potent tumorigenic activity. These results suggest that inhibition of 9,10-dihydrodiol formation, the influence of a 4-methyl substituent in directing dihydrodiol formation at the 1,2- or 7,8-positions, and the presence of a bay-region methyl group may be responsible for eliciting a tumorigenic response for 1,4-dimethylphenanthrene.

Animals↗

Magnocellular hypothalamic projections to the lower brain stem and spinal cord of the rat. Immunocytochemical evidence for predominance of the oxytocin-neurophysin system compared to the vasopressin-neurophysin system.

The paraventricular nucleus of the rat hypothalamus has been shown to project to the medulla and spinal cord. The proportion of oxytocin-neurophysin (OTNP) axons to vasopressin-neurophysin (VPNP) axons in these structures is unknown. A major difficulty in resolving this problem in previous immunocytochemical studies was the lack of a specific antiserum to each rat neurophysin. In this study two approaches have been used: (1) comparison of immunostaining for neurophysin in normal versus homozygous Brattleboro rats with diabetes insipidus (HODI) which lack VPNP, and (2) application of an antiserum to both rat neurophysins absorbed with HODI rat hypothalamic-pituitary extracts which contain only OTNP. The latter would result in an antiserum specific for VPNP. Our results indicate that the axons which constitute the caudal projections from the paraventricular nucleus are predominately oxytocinergic, the vasopressinergic innervation being limited to the nucleus tractus solitarius, the dorsal motor nucleus of vagus, and the substantia gelatinosa. A similar number of reactive fibers were seen in the medulla and spinal cord of normal and HODI rats. No positive perikarya were observed caudal to the hypothalamus. Fibers in the medulla appeared to terminate in the nucleus of the solitary tract and in the dorsal motor nucleus of the vagus nerve. Positive fibers throughout the cord were present in the substantia gelatinosa and in the intermediolateral grey. The possible role(s) of these projections in integrating autonomic functions and afferent information with neuroendocrine regulation is discussed.

Animals↗

Immunocytochemical distribution of corticotropin (ACTH) in monkey brain.

The distribution of adrenocorticotropin (ACTH) in monkey brain was examined by immunoperoxidase immunohistochemistry. An antiserum to ACTH that recognized the C-terminal portion of the molecule was used. Immunoreactive ACTH was visualized as an intraneuronal constituent with a widespread distribution throughout the brain. Reactive cell bodies were seen only in the region of the arcuate nucleus of the hypothalamus. Dense axonal networks were seen in the hypothalamus, mesencephalic gray, and in the region around the anterior commissure. No staining was seen in the cerebral cortex, cerebellum, hippocampus, or striatum. ACTH or fragments of ACTH may function as neurotransmitters or neuromodulators in primate brain.

Adrenocorticotropic Hormone↗

Comparative tumor initiating activity of 10-methylbenzo-[a]pyrene, 7,10-dimethylbenzo[a]pyrene and benzo[a]pyrene.

The tumor initiating activity on mouse skin of benzo[a]pyrene (BaP), 7,10-dimethylBaP, and 10-methylBaP was determined. Each compound was tested at initiating doses of 50 microgram and 100 microgram with promotion by application 3 times weekly of 2.5 microgram tetradecanoylphorbol acetate. BaP induced tumors in 40% (100 microgram) and 25% (50 microgram) of the animals. No tumors were observed in either group treated with 7,10-dimethylBaP. In the groups treated with 10-methyl-Bap, the incidence of tumor bearing animals was 20% at both doses. These results and the results of previous studies on other methylated BaP derivatives suggest that the mechanism of activation of these compounds is similar to that observed for the parent hydrocarbon and probably involves formation of an angular ring diol-epoxide or epoxide.

Animals↗

The strength of the reflex response to sinusoidal stretch of monkey jaw closing muscles during voluntary contraction.

1. Rhesus monkeys were trained to exert steady biting forces of 3--60 N for 1--2 sec. This behaviour was well maintained while sinusoidal or step opening and closing movements were imposed on the jaw. 2. The amplitude of the force modulation during sinusoidal stretching was divided by the amplitude of movement to obtain the magnitude of stiffness. This estimate was made at frequencies from 2 to 50 Hz at amplitudes of 100 and 500 micrometer (half the peak-to-peak movement at the incisors). 3. Peak magnitudes of stiffness were seen with frequencies of 8--15 Hz when the amplitude of movement was small; there was a great deal of variation between individual animals. This variation was most striking with mean forces of 25--35 N. The stiffness was greatest in animals that showed considerable spontaneous tremor, and the highest levels of stiffness were often recorded with frequencies near which tremor amplitude was large. A marked phase lag in the force response was often seen during small amplitude stretching at 8--30 Hz. 4. Estimates of stiffness for larger amplitude (500 micrometer) stretching showed less variation; the magnitude of stiffness showed maximum values below 10 Hz and a minimum at 15--30 Hz. Force always showed a phase lead on position although this lead became small in the frequency range where with smaller movement there had been phase lags. The magnitude of stiffness increased with increasing mean force. 5. Bilateral electrolytic lesions were made in the brain stems of three animals; they reduced by over 95% the expected number of cells in the mesencephalic nucleus of the fifth cranial nerve on either side. These lesions interrupted the afferent pathway for the stretch reflex and so abolished excitatory electromyogram (e.m.g.) responses to step stretches of the jaw closing muscles. 6. Such reflex responses as persisted after the lesions were small and inhibitory. E.m.g. silences followed both step stretch and release; the response to release was a 'load compensation' that could not be attributed to spindle afferents. 7. After the lesions the responses to movements of 100 micrometer showed neither negative values for the phase nor marked peaks in the stiffness magnitude at low frequencies; these features therefore take origin in the action of the stretch reflex. The stiffness that was measured after the lesions may be attributed to the non-reflex components resisting stretch, particularly to the properties of the contracting muscles. Thus, the phase of the force response was markedly advanced at all frequencies and the stiffness seen for 100 micrometer was similar to that for 500 micrometer. Stiffness increased with increasing mean force, as before surgery. 8. Vector subtraction of the stiffness seen at each frequency after interrupting the stretch reflex from that seen before doing so gave a quantitative estimate of the strength of the stretch reflex. The reflex activity calculated in this way showed attenuation and progressive phase lag as the frequency increased above 10 Hz...

Afferent Pathways↗

Identification and reduction of carcinogens in the respiratory environment.

Epidemiological studies have implicated three factors in the overall increase of lung cancer--tobacco, especially cigarette smoking, urban pollution and, to a lesser extent, certain industrial respiratory environments. Some data were discussed on carcinogenic industrial inhalants, and on the possible effect of urban pollution. The reduction of pollution and that of specific environmental agents is stressed. Laboratory studies on the identification of carcinogens in cigarette smoke and their reduction toward the "less harmful cigarette" represent a part of this aspect.

Air Pollution↗

Dibenz[b,e]oxepinalkanoic acids as nonsteroidal antiinflammatory agents. 1. 6,11-Dihydro-11-oxodibenz]b,e]oxepin-2-acetic acids.

A series of 6,11-dihydrodibenz[b,e]oxepin-2-acetic acids has been evaluated for both antiinflammatory and analgetic activity in the carrageenan paw edema and phenylquinone writhing assays. The requirements for optimal activity in this series appear rather specific: (a) an unsubstituted 6,11-dihydrodibenz[b,e]oxepin nucleus and (b) a carbonyl group in the 11 position. One derivative, 6,11-dihydro-11-oxodibenz[b,e]oxepin-2-acetic acid (11), has been selected for further study.

Animals↗