[Infective endocarditis with bivalvular involvement due to Erysipelothrix rhusiopathiae. Report of one case]. / Endocarditis infecciosa con compromiso bivalvular por Erysipelothrix rhusiopathiae.

The microbiology of infective endocarditis (IE) varies in different populations and depends on public health conditions and socioeconomic status. In low-income countries, oral Streptococci affect hearts with rheumatic valve disease in patients with poor dentition. In high-income countries, Staphylococci are the most common cause, affecting elderly and immunocompromised patients, or those with invasive devices. Gram - positive bacili as IE pathogens are unusual. Erysipelothrix rhusiopathiae is a Gram positive bacili. It causes skin diseases in domestic and farm animals, but in humans, is a very unusual pathogen. This infection is considered a zoonosis, since most cases are linked to direct contact with vector animals. We report a 62 year-old male patient with a history of exposure to animals, who developed an infective endocarditis with severe bivalve regurgitation and septic shock, requiring antimicrobials and surgical resolution. Erysipelothrix rhusiopathiae was isolated from blood and valve vegetation cultures. The patient had a successful evolution and was discharged from the hospital.

Endocarditis infecciosa con compromiso bivalvular por Erysipelothrix rhusiopathiae / Infective endocarditis with bivalvular involvement due to Erysipelothrix rhusiopathiae. Report of one case

The microbiology of infective endocarditis (IE) varies in different populations and depends on public health conditions and socioeconomic status. In low-income countries, oral Streptococci affect hearts with rheumatic valve disease in patients with poor dentition. In high-income countries, Staphylococci are the most common cause, affecting elderly and immunocompromised patients, or those with invasive devices. Gram - positive bacili as IE pathogens are unusual. Erysipelothrix rhusiopathiae is a Gram positive bacili. It causes skin diseases in domestic and farm animals, but in humans, is a very unusual pathogen. This infection is considered a zoonosis, since most cases are linked to direct contact with vector animals. We report a 62 year-old male patient with a history of exposure to animals, who developed an infective endocarditis with severe bivalve regurgitation and septic shock, requiring antimicrobials and surgical resolution. Erysipelothrix rhusiopathiae was isolated from blood and valve vegetation cultures. The patient had a successful evolution and was discharged from the hospital.

[Subdural empyema secondary to sinusitis]. / Empiema subdural como complicación de sinusitis.

Subdural empyema is a rare complication of sinusitis in children. Its clinical presentation represents a neurosurgical emergency and as a scarcely recognized entity a delayed diagnosis rapidly increases its fatal prognosis. We report the clinical and radiological course of an adolescent with a subdural empyema secondary to sinusitis. Clinical and radiological features, laboratory findings and outcome of this condition are discussed based in a review of previously reported cases.

Changes in serum levels of SHBG, endogenous ligands and levonorgestrel induced by ethinylestradiol in Norplant users.

This work was done in search for a model to examine target organ response to fluctuations in serum levels of sex hormone-binding globulin (SHBG) and its ligands. The time course and magnitude of fluctuations of SHBG, levonorgestrel (L-Ng), estradiol (E2), testosterone (T) and dihydrotestosterone (DHT) in serum were examined during and after treatment with 50 ug of ethinylestradiol (EE2) daily for 10 days in 10 volunteer women using NORPLANT implants. Six of these volunteers were also treated with 20 ug of EE2 daily for 7 days and two additional volunteers using a copper-T IUD were treated with 50 ug of EE2 daily for 7 days. In all cases, SHBG and L-Ng levels increased in a close parallel manner several-fold above basal levels during treatment, reaching a maximum around two days after the last EE2 pill. In contrast, the levels of E2 and T increased in one subject, decreased in 5 and remained unchanged in 4, while changes of DHT were unrelated to those of the other ligands. Since the L-Ng "secretion rate" by NORPLANT implants is constant, it follows that the effect of EE2 on its levels is due to a decreased metabolic clearance rate, most likely secondary to the increased binding of L-Ng to SHBG in serum. This interpretation is in agreement with the close parallelism in the fluctuations of L-Ng and SHBG. It is concluded that in NORPLANT users, SHBG and L-Ng, but not the endogenous ligands, behave in a predictable manner in response to EE2. Thus, this model affords the possibility of exploring the influence of SHBG on tissue response to progestins.

Clinical chemistry in women treated with progestogen implants.

Effects on metabolic parameters of six subdermal implants of d-norgestrel, norgestrienone (R2010) and methylnorgestrienone (R2323) were studied in women. In general, tests remained within the normal range. An exception was increases in serum transaminase levels in several subjects on R2323 implants. Average cortisol values showed a tendency to decrease on all three regimens, but remained within the significance only with R2323 at six months and R2010 at 12 months. Serum cholesterol levels showed significant decreases on R2010 implants.

Clinical chemistry in women treated with six levonorgestrel covered rods or with a copper IUD.

A group of women treated with six levonorgestrel covered rods participated in a study on general chemistry and blood levels of selected hormones at treatment months 20 and 65. A comparable group of Copper T users served as control. Parameters analyzed were the SMA 12 chemistry profile, estradiol, testosterone, cortisol, T3, T4 and TSH. Samples from treated and control subjects were drawn within the same calendar period and were run simultaneously for the assay of each parameter. The values observed were within the normal limits. Significantly higher values of total protein and albumin and lower levels of estradiol and testosterone were found among implant users when compared to the control group. The results suggests little or no metabolic changes in users of six levonorgestrel covered rods which release a daily dose of approximately 105 micrograms.

A longitudinal study on cortisol, prolactin and thyroid hormones in users of Norplant subdermal implants or a copper T device.

A longitudinal study was undertaken to assess PRL, cortisol, TSH, T3 and T4 levels in NORPLANT implant users (n = 22) and Copper T users (n = 20). Participants were healthy women with no contraindication for hormonal contraception. Samples were drawn at 0930 to 1000 h twice pretreatment and at month 2, 4, 6, 12, 24 and 36 after insertion. At the second treatment month, a second sample was obtained at 1600 h to assess cortisol diurnal variation. Hormones were measured by RIA. Values for all hormones were similar in Norplant and Copper T users. No significant changes occurred throughout the study period. Elevated PRL levels (greater than 500 mU/1) were found in three women from each group before and during treatment but no clinical evidence of hyperprolactinemia was detected. The results of this study reassure that long-term use of NORPLANT implants do not impair plasma levels of cortisol, prolactin and thyroid hormones.

Recovery of fertility and outcome of planned pregnancies after the removal of Norplant subdermal implants or Copper-T IUDs.

The recovery of fertility after discontinuation of NORPLANT implant use was assessed in ninety women who stated a desire for a new child at the time of removal. Three subjects were lost to follow-up after removal. The cumulative probability of conception in the remaining 87 women was 25, 49, 73 and 86 percent at one, three, six and twelve months after removal, respectively. Nine observations were censored either because of the use of a contraceptive method soon after removal of the implants (n = 7) or separation (n = 2). All other cases were pregnant at the end of two years with exception of three subjects where a male factor for infertility was present. There was no significant correlation between the length of NORPLANT use and the length of the interval from removal to conception. A significantly higher frequency of intervals longer than 6 months was observed among women older than 30 years as compared to younger women. Pathology during pregnancy was cholestasia (n = 5), hypertension (n = 1) and gestational diabetes (n = 1). The outcome was term delivery in 59 cases, premature delivery in 4 cases, and spontaneous abortion in 7 cases. One woman is still pregnant and the outcome is unknown in 4 cases. One premature infant died. A contemporary control group of Copper T users enrolled under the same criteria as NORPLANT implant users provided 44 women who had the device removed to become pregnant. The cumulative probability of pregnancy was 27, 69, 84 and 89 at one, three, six and twelve months and all were pregnant by the end of the second year. Six censored observations occurred because of the use of another contraceptive method after removal (n = 3) or loss to follow-up (n = 3). The outcome of pregnancy was term delivery in 23 cases and abortion in 7 cases. Recovery of fertility occurred at a normal rate after NORPLANT implant removal and the incidence of problems detected in the ensuing pregnancy were within the expected range for Chilean women.

Estradiol plasma levels during long-term treatment with Norplant subdermal implants.

Estradiol-(E2) plasma levels were assessed in forty-seven women treated for one through seven years with the same set of Norplant implants. Each woman was subjected to one (n = 34), two (n = 11) or three (n = 2) sampling runs. At each sampling run, blood samples were drawn every third or fourth day during 5 or 6 consecutive weeks. Sampling runs were classified as ovulatory (n = 11), anovulatory (n = 49) or uncertain (n = 1) according to progesterone levels. Controls were Copper T users (n = 8), all classified as ovulatory. No significant differences were found for the mean E2 levels between Norplant users and Copper T users and between ovulatory and anovulatory cases. The mean of the peak E2 value found in each sampling run was significantly higher in anovulatory Norplant subjects than in the control group. The mean of the minimum E2 level observed was significantly lower in Norplant cases than in Copper T users. A single woman from the Norplant group and none from the Copper T group had all E2 values below 370 pmol/l. The inhibition of the reproductive function induced by Norplant implants is associated with a wider range of E2 circulating levels. None of the values observed at the extremes should cause serious concerns. High peaks are transitory and opposed by the antiestrogenic effect of levonorgestrel. Persistent low levels which could be associated with a hypoestrogenic state were observed in a single case.

Clinical chemistry in women treated with levonorgestrel implants (Norplant) or a TCu 200 IUD.

Two groups of implant users and two groups of IUD users participated in the study at different times. In the first groups, fractionation of lipoproteins was performed on serum samples from 28 subjects who had used the implants for 37 months and from 26 subjects who had used the Copper TCu 200 for 30 months. Users of the implants had significantly lower levels of total cholesterol, triglycerides and LDL-cholesterol than users of the IUDs. HDL-cholesterol levels were not different between the groups. In the other groups of women, general chemistries and selected hormone assays were carried out on samples from 30 subjects who had used implants for 51 months and from 24 subjects who had used the TCu 200 IUDs for 43 months. The parameters studied were the SM-12 chemistry group profile, estradiol, cortisol, testosterone, triiodothyronine, thyroxine and thyroid stimulating hormone. In the implant group, mean serum glucose levels were statistically significantly elevated and inorganic phosphorus levels were significantly reduced as compared to the IUD group. In both cases all individual measurements were within the normal range for the population. Testosterone and triiodothyronine levels in the implant group were significantly lower than in the IUD group, but no individual values were outside the normal range for the population. Mean values for all other parameters were not significantly different between the groups.

PIP: 2 groups of implant users and 2 groups of IUD users participated in this study at different times. In the 1st groups, fractionation of lipoproteins was performed on serum samples from 28 subjects who had used the implants for 37 months and from 26 subjects who had used the copper TCu 200 for 30 months. Users of the implants had significantly lower levels of total cholesterol, triglycerides, and low density lipoprotein cholesterol than IUD users. High density lipoprotein cholesterol levels were not different between the groups. In the other groups of women, general chemistries and selected hormone assays were carried out on samples from 30 subjects who had used the implants for 51 months and from 24 subjects who had used the TCu 200 IUDs for 43 months. The parameters studied were the SMA-12 chemistry group profile, estradiol, cortisol, testosterone, triiodothyronine, thyroxine, and thyroid stimulating hormone. In the implant group, mean serum glucose levels were statistically significantly elevated and inorganic phosphorus levels were significantly reduced as compared to the IUD group. In both cases, all individual measurements were within the normal range for the population. Testosterone and triiodothyronine levels in the implant group were significantly lower than in the IUD group, but no individual values were outside the normal range for the population. Mean values for all other parameters were not significantly different between the groups.

A three-year clinical trial with levonorgestrel silastic implants.

Silastic implants containing the progestin, levonorgestrel, were tested as long-term contraceptives in 101 women. After three full years of exposure and 2,998 woman-months of use, no pregnancies had occurred. The continuation rates were 87% at 12 months, 79% at 24 months and 66% at 36 months. The most important side effect was excessive or irregular bleeding during the first year. No treatment was offered for this side effect other than vitamins and iron or change of method, with the exception of 3 cases where ethinyl estradiol was used one time for 2 weeks each. Bleeding disturbances led 8 patients to ask for removal of implants. Other side effects were headache, acne and lower abdominal pain. Blood and urine analysis tested 17 different parameters and all but plasma cortisol remained within normal limits throughout the study. A general tendency toward lowered cortisol values was observed and two subjects had more than one value below the normal limit for the population during the study. Glucose tolerance tests during the second year were abnormal in two women with familial diabetes but they returned to normal values spontaneously at the next test. It is concluded that levonorgestrel implants offer effective protection against pregnancy during the first three years of continuous use. Their acceptability and few side effects justify larger trials, especially if treatment of bleeding irregularities is introduced.

Bleeding pattern, outcome of accidental pregnancies and levonorgestrel plasma levels associated with method failure in Norplant implants users.

The aim of this study was to characterize the bleeding pattern, the outcome of pregnancies and the levonorgestrel plasma levels associated with method failures in Norplant implants users. Nineteen pregnancies are reported in 458 woman and 21,589 woman-months observed during the first eight years of Norplant use. Pregnancy rates increased slightly during the first six years of use, attaining a Pearl Index above three thereafter. All women who became pregnant had experienced a regular bleeding pattern in the six months preceding conception. Levonorgestrel plasma levels observed at different intervals before conception and during the conceptional cycle were similar to those observed in non-pregnant women at comparable intervals after Norplant insertion. The nineteen pregnancies ended in thirteen term deliveries, one premature delivery, three abortions and two ectopic pregnancies. No abnormalities were found in the infants. The two ectopic pregnancies are the only ones reported for Norplant users in The Population Council studies. The overall incidence is less than 0.8 per 1000 woman-years.

Long-term follow-up of women treated with Norplant implants.

This report describes the long-term follow-up of 376 women who received NORPLANT implants in the period October 1974 through May 1979. One-hundred-and-ten subjects received replacement implants after variable lengths of use of the first set. The average levonorgestrel plasma levels declined steadily through eight years of use of NORPLANT capsules (r = -.937). Values were 0.35 ng/ml, 0.29 ng/ml and 0.22 ng/ml at treatment years 1, 5 and 8, respectively. Levonorgestrel plasma levels after replacement with a second set of implants were similar to those observed after the first insertion, either when placed in the same site as the first set or in a different area. Nineteen pregnancies occurred during 18,530 woman-months of use of the first set of implants, eleven of them during years 6 through 8 of treatment. The Pearl Index for the first 5 years of NORPLANT implants use was 0.63. No pregnancy has occurred in 4194 woman-months observed during treatment with a second set of capsules. Fifty-six women (14.9%) out of 376 acceptors of the first implant and 10 (9.1%) out of 110 acceptors of the replacement implants were terminated for other medical reasons, mainly bleeding problems and side effects commonly associated with hormonal contraception. Two women died while using NORPLANT implants, one of a cardiac arrest after surgery for a gallbladder disease and one because of endocranial hypertension originating from the rupture of an aneurism of the median cerebral artery. The bleeding pattern observed in the three months after NORPLANT capsules replacement was similar to that observed in the 90 days before replacement and different from that experienced by the same women in the first 90 days of implant use. This finding can be interpreted as an indicator of adaptive changes experienced by the target organs during long-term continuous administration of levonorgestrel. The prompt recovery of fertility after removal of NORPLANT implants suggests that these changes are reversible.

Four-year experience in a randomized study of the Gyne T 380 Slimline and the Standard Gyne T 380 intrauterine copper devices.

Performance of the Slimline and Standard models of the Gyne T 380 were measured through four years in a comparative study initially involving 996 women, seventy percent of whom were randomized to the Slimline device. Cumulative pregnancy rates of Slimline users were 0.3 +/- 0.2 per 100 both at three and at four years, as compared with rates of 1.5 +/- 0.9 and 3.8 +/- 1.7 at the same intervals for users of the Standard model (P > .05). The four-year explusion rate of the Slimline, 8.6 +/- 1.3 per 100, was significantly higher than the comparable rate of the Standard model, 4.4 +/- 1.6 (P < .05). The two Gyne T* models did not differ in continuation rates. First time IUD users, however, had substantially lower continuation rates than did former users (P < .001), in consequence of their relative youth and desire to have additional children. Other performance measures did not differ importantly by device.

Clearance of levonorgestrel from the circulation following removal of NORPLANT subdermal implants.

The disappearance of levonorgestrel from plasma after the removal of NORPLANT subdermal implants was studied in 12 women who had been treated from 5.5 to 78 months. The existence of one or two half-lives for the rate of disappearance was assessed. The influence of body weight, body fat and length of treatment upon levonorgestrel clearance was studied through stepwise regression analysis. It was found that the levonorgestrel decay rate after implant removal can be entirely accounted assuming one half-life of 42 +/- 16 h (mean +/- SD; range 13 to 62 h). Stepwise regression analysis showed that levonorgestrel half-life is positively correlated with body weight and not significantly correlated with the length of treatment or body fat. It is concluded that, after long-term administration of levonorgestrel via subdermal implants, the major part of the steroid is cleared from plasma within 96 h and that only trace amounts are detected in the following days.

Clinical trial with subdermal implants containing norgestrienone.

Norgestrienone implants delivering approximately 225 microgram/ day were tested clinically for contraceptive effectiveness and acceptability in 145 women. Five pregnancies occurred in 2259 woman-months of use, one in the 11th month, one in the 15th and three in the 16th month of use. Continuation rate at 12 months was 86.7. The number of bleeding runs and bleeding days was increased in approximately 12% of the subjects. Ten percent of the patients had no bleeding in the first 90 days of treatment. Changes in bleeding pattern led to closures in four cases. Headache and signs of mild androgenicity were among the leading side effects. Blood and urine analysis throughout the study showed normal values of 17 different parameters, but a tendency to lower cholesterolemia not associated with changes in thyroid hormone levels, was observed in several patients. Cortisol was found slightly under the lower normal range in one subject without clinical manifestations of hypoadrenalism. It is concluded that norgestrienone implants should be replaced every twelve months for maximal contraceptive effect and because of their efficacy and good acceptability, evaluation of their long term use is warranted.

Clinical trial with subdermal implants of the progestin R-2323.

PIP: 6 3 cm polydimethylsiloxane capsules containing 30 mg each of R-2323 were implanted subdermally in each of 38 women to assess their effect upon fertility, menstrual pattern, some aspects of metabolism, and the incidence of side effects associated with the use of this hormonal contraceptive. There were zero pregnancies in a total of 292 months of exposure. The longest duration of use was 12 months and the median was between 8-9 months. Amenorrhea and signs of androgenicity such as acne and hyperthricosis were common complaints and a frequent reason for closure. Headache and nervousness also were reported by a high proportion of patients. Blood and urine analysis were normal with the exception of elevated transaminases in 20 out of 27 patients after the 3rd month of treatment. Side effects and elevation of the serum transaminase levels disappeared promptly after removal of the implants in all cases. It is concluded that R-2323 implants at the dose tested are potent inhibitors of fertility in women. The high incidence of treatment-associated adverse reactions impose limitations on their use in Chilean women.^ieng

A five-year clinical trial of levonorgestrel silastic implants (Norplant TM).

Silastic implants containing the progestin, levonorgestrel, were tested as a long-term contraceptive system in 101 women. During five full years of use, no pregnancies occurred. The 5-year continuation rate was 54%. Menstrual irregularities were the most frequent reason for termination of use but only during the first year. More than half of the terminations for this reason were in the first year. Some of the subjects elected to continue use of the implants beyond 5 years, allowing release rate data to be obtained through 6 years. From the second through the sixth year of use, the implants delivered a constant 30 micrograms per day of levonorgestrel to the subjects, and even after six years 57% of the original steroid content remained in the capsules. Return of fertility following removal was essentially immediate and not related to time of use. Medical reasons for removal were infrequent and no pattern was discernible.

PIP: Silastic implants containing the progestin, levonorgestrel, were placed under the skin of the anterior forearm and tested as a longterm contraceptive system in 101 women. During 5 full years of use, no pregnancies occurred. The 5-year continuation rate was 54%. Menstrual irregularities were the most frequent reason for removal during the 1st year when they caused more than 1/2 the terminations. Some of the subjects elected to continue use of the implants beyond 5 years, allowing release rate data to be obtained through 6 years. From the 2nd through 6th year of use, the implants delivered a constant 30 mcg/day of levonorgestrel to the subjects and even after 6 years, 57% of the original steroid content remained in the capsules. Return of fertility following removal was essentially immediate and not related to time of use. Medical reasons for removal were infrequent and no pattern was discernible.

Clinical trial with 3-keto-desogestrel subdermal implants.

The study was done to assess the clinical performance and in vivo steroid release rate of 3-keto-desogestrel subdermal implants designed to deliver 5 different doses of the progestin. Volunteers were healthy women of proven fertility who provided blood samples at scheduled intervals during treatment. No pregnancy occurred in 514 woman-months in users of implants delivering 30 and 40 micrograms per day of 3-keto-desogestrel. Three pregnancies, one ectopic, were observed in 109 woman-months recorded with implants delivering 20 micrograms per day or less. Ovulation was inhibited, as judged by depressed progesterone levels, in 57 of 59 (97%) blood samplings in women whose 3-keto-desogestrel plasma levels were greater than 0.28 nmol/L and in 39 of 75 (52%) of cases with lower levels. Users of 4 cm implants manufactured by The Population Council, New York, showed mean levels above 0.28 nmol/L until 18 months of use. Levels achieved with 4.4 cm implants manufactured by Organon, Oss, Holland, were less consistent. No changes were observed in the plasma lipoprotein pattern or clinical chemistry during treatment. The main complaint was the occurrence of bleeding irregularities, particularly with the lower doses. Ovarian cysts found during pelvic examination in 11 (22%) subjects disappeared spontaneously within 7-90 days. 3-keto-desogestrel implants releasing around 40 ug/day and providing plasma levels around 0.28 nmol/L afford efficient contraceptive protection.

Clinical assessment of treatments for prolonged bleeding in users of Norplant implants.

The effectiveness of three drugs in controlling prolonged bleeding in the first year of NORPLANT implants use was tested. The drugs were levonorgestrel (L-Ng, 0.03 mg twice a day for 20 days), ethinylestradiol (EE, 0.05 mg per day for 20 days) and ibuprofen (Ib, 800 mg three times a day for 5 days) and were given orally. A control group received a placebo (PL, one pill of lactose for 20 days). Treatment should start each time a woman experienced eight consecutive days of bleeding or spotting. The 183 volunteers were not aware of the drug administered. A daily record of bleeding and spotting and of treatment intake was maintained. One-hundred-forty women completed the study period; 60 never used the prescribed treatment. Women treated with the three test drugs had significantly fewer bleeding and spotting days during the treated month and also throughout the study year than women using the placebo. The mean number of bleeding plus spotting days per actually treated subject in the first year was 77, 94, 101 and 129 days for the EE, Ib, L-Ng and PL groups, respectively. The administration of EE might help in the management of prolonged bleeding during the first year of NORPLANT implants use.