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Infections caused by Actinomyces organisms have been demonstrated to occur in association with IUD use. Uterine actinomycosis infection is usually superficial, but it is potentially invasive. It may prove fatal. When Actinomyces is detected in a vaginal Papanicolaou smear, establishment of the correct diagnosis followed by IUD removal and appropriate antibiotic therapy are recommended. A case history is presented of a 28 year old woman who had been using an IUD and who had systemic Actinomyces infection and a brain abscess develop several years after removal of her uterus and fallopian tubes. The woman was referred to the Johns Hopkins Hospital in Baltimore in 1977 for evaluation of headaches and grand mal seizures. 4 years earlier, in 1973, she had been seen at another hospital with a recent weight loss of 18 kg. She was found to have a tubo-ovarian abscess, for which she underwent a hysterectomy, bilateral salpingectomy, and unilateral oophorectomy. At the time of surgery, an IUD was in place. A histopathological diagnosis of botryomycosis tubo-ovarian abscess was made on submitted tissues. She received no antibiotic therapy. In 1975, pulmonary infiltrates developed that were attributed to bronchopneumonia. She was treated with a short course of tetracycline hydrochloride. Later that year she was thought to have sarcoidosis and was treated for 1 year with several doses of prednisone. Clinically, her condition remained stable until March 1977, when a pyogenic subcostal abscess was drained. In July 1977, she had headache, dizziness, generalized seizures, and an incomplete right homonymous hemianopsia develop. A craniotomy for excision and drainage of an abscess was performed. The presence of Actinomyces israelii in brain tissue was confirmed by direct immunoflourescence using specific antiserum. It was confirmed that Actinomyces had been present at the time of her 1st surgical procedure. She was treated with high doses of intravenous penicillin G potassium for the first 4 weeks, followed by lower doses of oral penicillin V potassium for an additional 15 months. She recovered completely, except for a persistent right homonymous hemianopsia. The case illustrates that systemic dissemination and potentially life threatening complications of uterine actinomycosis can occur if the infection is unrecognized and/or inadequately treated.
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PMID:Systemic Actinomyces infection. A potential complication of intrauterine contraceptive devices. 712 Jun 9

The general pharmacological properties of a novel cognition-enhancing agent, nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) were investigated, and the following results were obtained. 1. Central nervous system: Nefiracetam showed depressant activities (such as ataxia) on general behavior (mice), and inhibited spontaneous locomotor activity, rota-rod and traction performances (mice) and polysynaptic potential of the spinal reflex (rats), and potentiated pentobarbital anesthesia (mice). The drug inhibited electroshock-induced seizure at relatively low doses, but did not affect chemoshock-induced seizure (mice). Nefiracetam failed to show analgesic activity in the tail pinch test, but inhibited the acetic acid-induced writhing syndrome (mice). An inhibitory pattern in the electroencephalogram was observed (cats). Nefiracetam had little or no effect on body temperature (rats). 2. Respiratory and cardiovascular systems: Nefiracetam induced transient decreases in blood pressure, left ventricular pressure and LV dp/dt max at higher doses (dogs). 3. Autonomic nervous system: Nefiracetam had no influence on pupil size (rabbits). The drug induced no significant effect on the pressor response to norepinephrine or depressor response to acetylcholine, but inhibited the contractile response of the nictitating membrane to preganglionic cervical sympathetic nerve stimulation at the highest dose (dogs). 4. Gastrointestinal system: Nefiracetam inhibited gastrointestinal propulsion (mice), gastric emptying rate and gastric secretion (rats) at higher doses. Nefiracetam produced no apparent damage in the gastric mucosa, and had no effect on bile secretion (rats). 5. Isolated smooth muscle: Nefiracetam had no effect on the resting tonus of isolated ileum, whereas it inhibited the contractile response to acetylcholine, histamine, serotonin, nicotine and BaCl2 at higher concentrations (guinea pigs). Nefiracetam had no effect on the resting tonus or the serotonin-induced contraction of stomach fundus (rats). The drug had no effect on the resting tonus or the norepinephrine-induced contraction of vas deferens, but tended to inhibit the contraction induced by nerve stimulation (guinea pigs). Nefiracetam had little or no effect on the resting tonus or oxytocin-induced contraction of virgin uterus, or on spontaneous contraction of pregnant uterus (rats). Nefiracetam did not affect the resting tonus of trachea, whereas it inhibited isoproterenol-induced relaxation at the highest concentration (guinea pigs). Nefiracetam had no chronotropic effect in isolated atria, but showed a slight negative inotropic effect at the highest concentration (guinea pigs). 6. Miscellaneous: Nefiracetam slightly decreased urinary volume, whereas it did not affect urinary electrolyte excretion (rats).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:General pharmacological profile of the new cognition-enhancing agent nefiracetam. 801 90

The objectives of this study were to determine if infants delivered with severe acidemia (cord umbilical arterial pH < 7.0) had short-term neurologic effects and whether infants with persistent bradycardia who received cardiopulmonary resuscitation (CPR) in the delivery room would be at greatest risk for subsequently developing neonatal seizures. Forty-seven infants (39 term, 8 preterm) delivered with severe fetal acidemia were studied. The mean (+/- S.D.) for pH, PaCO2, and base deficit for the 47 infants was 6.86 +/- 0.11, 97 +/- 22 mm Hg, and -17 +/- 4, respectively. Labor complications were common and included placental abruption in 8, ruptured uterus in 4, cord prolapse in 3, fetal heart rate decelerations in 12, and other (n = 14). Most infants were delivered via emergency cesarean section (n = 29). Delivery room interventions included oxygen and bag/mask ventilation only (n = 20) and intubation and ventilation (n = 22); 7 of 22 infants received CPR and epinephrine for persistent bradycardia (heart rate < 80 beats/min despite ventilatory support). Five infants required no intervention. Eight infants (17%) had seizures; 6 of these infants received CPR in the delivery room. Short-term outcomes were abnormal in 7 of 8 infants (i.e., death in 5, abnormal neurologic examination at discharge in 2). In 39 infants without seizures, 32 had transient neurologic abnormalities (i.e., irritability, hyperreflexia, proximal hypotonia) which resolved by discharge, and 2 had abnormal and 5 normal examinations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Severe fetal acidemia: neonatal neurologic features and short-term outcome. 821 39

General pharmacological effects of recombinant human basic fibroblast growth factor (bFGF) were investigated. 1. Central nervous system: Basic FGF produced almost no effect on the general symptoms and behaviors of mice. Basic FGF did not influence the spontaneous motor activity, hexobarbital-induced anesthesia, electroshock seizure threshold, pentylenetetrazole-induced seizure in mice and normal body temperature and spinal reflex in rats up to a dose of 1 mg/kg (s.c., i.v.). As regards pain sensation, it inhibited the acetic acid-induced writhing at 1 mg/kg (s.c.). No abnormal waves were observed in spontaneous EEG of the rabbit up to 1 mg/kg (i.v.) of bFGF, but at 0.1 mg/kg it had a slight effect on the ratio of EEG levels and at 1 mg/kg induced an increase in rest period, disappearance in the period of fast wave sleep and a decrease in the period of deep sleep. 2. Somatic nervous system: Basic FGF did not influence the corneal reflex, twitch response of the skin and diaphragm-phrenic nerve preparations. 3. Autonomic nervous system and smooth muscle: Basic FGF showed little effects on the spontaneous movement of the isolated ileum, contraction induced by various agonists in isolated ileum, resting tension and noradrenaline(NA)-induced contraction of the aorta, resting tension and histamine-induced contraction of isolated trachea, spontaneous movement and 5-HT-induced contraction of isolated strips of stomach fundus, NA-induced contraction of isolated vas deferens of the rat up to the concentration of 10(-4) g/ml. Basic FGF augmented the tone of the isolated non-pregnant uterus at the concentrations of 10(-5) g/ml and above and inhibited or tended to inhibit the contractile tension of non-pregnant or pregnant uterus at 10(-4) g/ml, but it did not influence the spontaneous movement of the uterus, either the non-pregnant or pregnant, under in situ conditions even at a dose of 1 mg/kg (i.v.). Basic FGF did not influence the pupil size. 4. Respiratory and circulatory systems: Basic FGF had no effect on the isolated heart. The influence was not exerted on the heart rate for the isolated atria but slight inhibition of contractile force was observed at 10(-4) g/ml. In anesthetized dogs a decrease in blood pressure, a slight increase in heart rate and respiratory rate and a decrease in femoral blood flow were observed at 0.01 and 0.1 mg/kg (i.v.) of bFGF Similarly, a slight increase in heart rate and a slight decrease of blood pressure were observed at 1 mg/kg (s.c.) in conscious rats. 5. Digestive system: Administration of bFGF at 1 mg/kg did not result in changes in the transport capacity within the gastrointestinal tract (s.c., i.v.) and the secretion of the gastric juice (s.c.). 6. Urine output and electrolyte metabolism: Basic FGF produced a decrease in urinary Na+ excretion at 1 mg/kg (s.c.), and showed a tendency to increase in urinary volume at 0.01 and 0.1 mg/kg (i.v.). At 1 mg/kg (i.v.) urinary excretion of Na+ and Cl- was decreased significantly. It had no effect on the ability of rats to excrete PSP (phenol red) up to 1 mg/kg (s.c.). 7. Blood system: Basic FGF did not influence the coagulation time of the whole blood, prothrombin time and activated partial thromboplastin time of rats up to 1 mg/kg (s.c., i.v.). It did not influence the aggregation of rabbit platelets induced by collagen and ADP up to 10(-4) g/ml. Basic FGF at concentration of 10(-4) g/ml exhibited no hemolytic action. 8. Local action: Plantar subcutaneous injection of bFGF at above 0.005 mg/site induced edema by itself on and after the next day, and also reinforced carrageenin-induced edema from 1 day after injection. The results show that bFGF did not produce any acute effects on the somatic nervous system, autonomic nervous system, smooth muscle and blood system. In contrast, bFGF produced slight effects on the circulatory system, central nervous system and kidney function when injected systemically. Subcutaneous administration may produce edema at the s
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PMID:General pharmacology of recombinant human basic fibroblast growth factor. 884 46

This review touches on the historical links between epilepsy, seizures and the uterus and ovaries which have fascinated and misled physicians since Greco-Roman times. It then examines present knowledge of ovarian function and its effect on epileptic activity and vice versa before exploring the modern controversy about polycystic ovaries and the polycystic ovary syndrome, epilepsy and anticonvulsant medication. Based on present evidence, women with epilepsy are more prone to develop polycystic (polyfollicular) ovaries than other women due to the epilepsy itself. But women with epilepsy related polycystic (polyfollicular) ovaries are vulnerable to the effects of sodium valproate (possibly particularly during adolescence) and may develop the polycystic ovary syndrome: this is reversible if the valproate is withdrawn. Lamotrigine and carbamazepine seem to prevent the development of the syndrome.
Seizure 2001 Apr
PMID:Epilepsy and the ovary (cutting out the hysteria). 1143 23

This review touches on the historical links between epilepsy, seizures and the uterus and ovaries which have fascinated and misled physicians since Greco-Roman times. It then examines present knowledge of ovarian function and its effect on epileptic activity and vice versa before exploring the modern controversy about polycystic ovaries and the polycystic ovary syndrome, epilepsy and anticonvulsant medication. Based on present evidence, women with epilepsy are more prone to develop polycystic (polyfollicular) ovaries than other women due to the epilepsy itself. But women with epilepsy related polycystic (polyfollicular) ovaries are vulnerable to the effects of sodium valproate (possibly particularly during adolescence) and may develop the polycystic ovary syndrome: this is reversible if the valproate is withdrawn. Lamotrigine and carbamazepine seem to prevent the development of the syndrome.
Seizure 2002 Apr
PMID:Epilepsy and the ovary (cutting out the hysteria). 1218 60

1-Trans-delta(9)-tetrahydrocannabinol (THC) was nominated by the National Cancer Institute to the NTP for study because it is the major psychoactive component of marijuana and a widely used Schedule I substance. Male and female F344/N rats and B6C3F1 mice received THC (97% pure) in corn oil by gavage for 13 weeks, 13 weeks with a 9-week recovery period, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood cells. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats received 0, 5, 15, 50, 150, or 500 mg THC/kg body weight in corn oil by gavage, 5 days per week for 13 weeks. Six male and six female rats receiving 500 mg/kg died before the end of the study. The final mean body weights and weight gains of all dosed groups of males and females, except 5 mg/kg females, were significantly lower than those of the controls. Feed consumption by dosed groups was similar to that by controls. Clinical findings observed during the study included lethargy, sensitivity to touch, convulsions, tremors, and aggressiveness. There were no clinical pathology differences considered to be directly related to the administration of THC. The absolute and relative uterus weights of 50, 150, and 500 mg/kg females were significantly lower than those of the controls. Treatment-related multifocal atrophy was observed in the testes of 150 and 500 mg/kg males; uterine and ovarian hypoplasia observed in 150 and 500 mg/kg females was also considered to be related to THC administration. Based on final mean body weights and mortality observed in the 13-week study, doses selected for the 2-year rat study were 12.5, 25, and 50 mg/kg. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice received 0, 5, 15, 50, 150, or 500 mg THC/kg body weight in corn oil by gavage, 5 days per week for 13 weeks. There were no treatment-related deaths. The final mean body weight and weight gain of 500 mg/kg males were significantly lower than those of the controls. Clinical findings included lethargy and aggressiveness, and both male and female mice in all dosed groups were easily startled. There were no absolute or relative organ weight differences, clinical pathology differences, or microscopic changes observed that were considered to be related to the administration of THC. Due to the minimal THC-related effects observed in the 13-week study, doses selected for the 2-year mouse study were 125, 250, and 500 mg/kg. 13-WEEK WITH 9-WEEK RECOVERY STUDY IN RATS: Groups of 10 male and 10 female rats received 0, 5, 15, 50, 150, or 500 mg THC/kg body weight in corn oil by gavage, 5 days per week for 13 weeks, and then were allowed to recover during a 9-week treatment-free period. Five male and eight female 500 mg/kg rats, five male and two female 150 mg/kg rats, and three male and two female 50 mg/kg rats died before the end of the study. During the 13-week dosing period, mean body weight gains of all dosed groups of rats were lower than those of the controls but returned to normal during the recovery period. Final mean body weights of all dosed groups were similar to those of the controls. Clinical findings observed during the recovery period included sensitivity to touch, convulsions, and aggressiveness. The absolute right testis weight of 500 mg/kg males was significantly lower than that of the controls. Treatment-related multifocal atrophy of the testis was observed in 150 and 500 mg/kg males. There were no treatment-related lesions observed in females administered THC. 13-WEEK WITH 9-WEEK RECOVERY STUDY IN MICE: Groups of 10 male and 10 female mice received 0, 5, 15, 50, 150, or 500 mg THC/kg body weight in corn oil by gavage, 5 days per week for 13 weeks, and then were allowed to recover during a 9-week treatment-free period. The final mean body weights of all dosed groups were similar to those of the controls. Clinical findings observed during the study included lethargy and aggressiveness, and both male and female mice in all dosed groups were easily startled. The absolutebsolute and relative uterus weights of 150 and 500 mg/kg female mice were significantly lower than those of the controls, as was the absolute uterus weight of 50 mg/kg females. 2-YEAR STUDY IN RATS: Groups of 62 vehicle control male rats, 60 low-dose male rats, 70 mid- and high-dose male rats, and 60 female rats were administered 0, 12.5, 25, or 50 mg THC/kg body weight in corn oil by gavage for 104 to 105 weeks. Nine or ten animals from each group were evaluated at 15 months. Survival, Body Weights, and Clinical Findings: Survival of all dosed groups was generally significantly greater than that of the controls. Mean body weights of dosed groups of males and females were lower than those of the controls throughout the study. Convulsions and seizures were observed in all dosed groups of male and female rats, usually following dosing or handling. Hematology and Clinical Chemistry: At the 15-month interim evaluation, total leukocyte and lymphocyte counts in all dosed groups of females were greater than those of the controls, and platelet counts in these groups were lower than that of the controls. Levels of follicle stimulating and luteinizing hormones in all dosed groups of males were significantly greater than those of the controls, as was the serum corticosterone level of 25 mg/kg females. Pathology Findings: No increased incidences of neoplasms were considered related to administration of THC. The incidences of mammary gland fibroadenoma and uterine stromal polyps were decreased in dosed groups of females, as were the incidences of pituitary gland adenomas, interstitial cell adenomas of the testis, and pancreatic adenomas in dosed males. 2-YEAR STUDY IN MICE: Groups of 62 vehicle control male mice, 60 low-dose male mice, 61 mid-dose male mice, and 60 high-dose male mice and 60 female mice were administered 0, 125, 250, or 500 mg THC/kg body weight in corn oil by gavage for 104 to 105 weeks (males) or 105 to 106 weeks (females). Survival, Body Weights, and Clinical Findings: Survival of 500 mg/kg males was significantly less than that of the controls; survival of all other groups of males and of all dosed groups of females was similar to that of the controls. Mean body weights of all dosed groups were markedly lower than those of the controls throughout the study. Clinical findings in dosed groups included hyperactivity, convulsions, and seizures which occurred following dosing or handling. Hematology: At the 15-month interim evaluation, total leukocyte and lymphocyte counts in all dosed groups of males were significantly lower than those of the controls. Pathology Findings: Increased incidences of thyroid gland follicular cell adenoma occurred in 125 mg/kg males and females, but the increase was not dose-related. Increased incidences of thyroid gland follicular cell hyperplasia occurred in all dosed groups of males and females. Increased incidences of forestomach hyperplasia and ulcers occurred in all groups of males administered THC. Incidences of hepatocellular adenoma and of hepatocellular adenoma or carcinoma (combined) occurred with a significant negative trend in male and female mice, as did incidences of eosinophilic foci and fatty change in the liver. GENETIC TOXICOLOGY: THC was not mutagenic in Salmonella typhimurium strains TA97, TA98, TA100, or TA1535 with or without rat and hamster liver S9 fractions. In cultured Chinese hamster ovary cells, THC induced sister chromatid exchanges at the highest dose tested in the presence of S9; at this dose level, cell cycle delay indicative of toxicity was observed. THC did not induce chromosomal aberrations in cultured Chinese hamster ovary cells with or without S9 metabolic activation enzymes. In vivo, no increase in the frequency of micronucleated erythrocytes was observed in the peripheral blood of male or female mice administered THC by gavage for 13 weeks. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of 1-trans-delta(9)-tetrahydrocannabinol in male or female F344/N rats administered 12.5, 25, or 50 mg/kg. There was equivocal evidence of carcinogenic activity of THC in male and female B6C3F1 mice based on the increased incidences of thyroid gland follicular cell adenomas in 125 mg/kg groups. Increased incidences of thyroid gland follicular cell hyperplasia occurred in male and female mice, and increased incidences of hyperplasia and ulcers of the forestomach were observed in male mice. The incidences of mammary gland fibroadenomas and uterine stromal polyps were decreased in dosed groups of female rats, as were the incidences of pancreatic adenomas, pituitary gland adenomas, and interstitial cell adenomas of the testis in dosed male rats and liver neoplasms in dosed mice. These decreases were likely related to lower body weights in dosed animals. Synonyms: 3-Pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6h-dibenzo(b,d)pyran-1-ol; delta1-tetrahydrocannabinol; (-)-delta1-3,4-trans- tetrahydrocannabinol; delta(9)-tetrahydrocannabinon; THC; delta1-THC; delta(9)-THC
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PMID:NTP Toxicology and Carcinogenesis Studies of 1-Trans-Delta(9)-Tetrahydrocannabinol (CAS No. 1972-08-3) in F344 Rats and B6C3F1 Mice (Gavage Studies). 1259 29

Intrapartum emergencies are challenging to all perinatal nurses because of the increased risk of adverse outcomes for the mother and fetus. Perinatal emergencies, such as seizures, amniotic fluid embolus, hemorrhage, and uterine rupture, create physiological challenges and trigger intrinsic survival techniques. The pregnant uterus becomes a vital source of blood volume during hypovolemic events because it is not considered a vital organ. The pregnancy itself may become burdensome, and birth may occur as an intrinsic maternal compensatory mechanism. The resultant fetal hypoxemia may also stress the fetus into initiating labor. During extensive oxygen desaturation and decompensation, the focus should be on maternal stabilization, which will subsequently enhance fetal stabilization. Clinical assessments, critical thinking, decision making, and resource allocation must be quick and appropriate to increase the likelihood of a positive outcome for the mother, fetus, and neonate.
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PMID:Intrapartum emergencies. 1464 1

We describe a 20-year-old 46,XY woman, with clinical findings of Fraser syndrome and three mitochondrial DNA (mtDNA) mutations of Leber hereditary optic neuropathy. The patient had microphthalmia, blindness, widely spaced nipples, bifid ureter, syndactyly of the toes, and mental retardation. Sonography showed the presence of a uterus and intra-abdominal gonads. The proband was screened for mtDNA mutations because of chronic gastrointestinal pseudo-obstruction, urinary tract dysmotility, seizures, mental retardation and persistent macrocytosis, as well as the intermittent elevation of methylmalonic acid. Analysis of point mutations by multiplex polymerase chain reaction and allele-specific oligonucleotide dot-blot hybridization revealed three homoplasmic mtDNA mutations, T14484C, T4216C, and T3394C. This represents a unique case with sex reversal, Fraser-like syndrome, and mitochondrial disease.
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PMID:Mitochondrial DNA mutations in a patient with sex reversal and clinical features consistent with Fraser syndrome. 1569 63

A postpartum mare and foal were presented for evaluation of fever and lethargy in the mare. The mare was diagnosed with endometritis and initially responded well to treatment. On the second day of hospitalization, the mare developed renal insufficiency characterized by oliguria, azotemia, hemolysis, and thrombocytopenia. Concurrently, the foal developed rapidly progressive central nervous system signs culminating in refractory seizures. Both animals failed to respond to treatment and were euthanized. Thrombotic microangiopathy involving glomeruli was evident on microscopic examination of the mare's kidneys. Microscopic evidence of brain edema was the principal postmortem finding in the foal. No specific etiology was confirmed in either case. Notably, Escherichia coli 0103:H2 was isolated from the mare's uterus and the gastrointestinal tracts of both animals. To the authors' knowledge, this is the first report in which an organism implicated as a cause of hemolytic-uremic syndrome was isolated from an animal with clinical signs and postmortem findings consistent with the disease.
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PMID:Hemolytic-uremic syndrome in a postpartum mare concurrent with encephalopathy in the neonatal foal. 1831 42


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