Infectious complications of intrauterine insemination: a case report and literature review.

Intrauterine insemination is commonly performed in the treatment of infertility. Infectious complications associated with intrauterine insemination are frequently cited, though rarely reported. A review of the literature yields only five reported cases of pelvic infections subsequent to intrauterine insemination (IUI), and only two of these show firm evidence of infection, with none presenting bacteriologic confirmation. We report a case of Escherichia coli septicemia subsequent to an IUI performed on a patient with a large adenomyoma. Of 147 patients treated with IUI at Georgetown University from November 1987 through March 1990, this was the only infectious complication. The incidence of infectious complications in our series is thus 0.0068 (6.8 per 1,000 women). A review of infectious complications in 38 reported series on intrauterine inseminations reveals five infections in 3,129 patients. With the addition of our series to the literature, the prevalence of infectious complications is 1.83 per 1,000 women undergoing IUI. The rates were not significantly altered by semen washing with antibiotics, or the administration of prophylactic antibiotics to the woman (P = .81). We conclude that (1) the infection rate following IUI is small, (2) many of the infections subsequent to insemination were not associated with intrauterine insemination, (3) most reported cases of infection fail to show evidence for the actual presence of infection, and (4) the prevalence is unaltered by the administration of prophylactic antibiotics or washing the semen sample with antibiotics.     

Thrombin Inhibition in discordant xenograft rejection

Abstract: Microvascular thrombosis and the associated platelet and endothelial cell activation are prominent observations in xenograft rejection. This pathological picture could be related to the excessive generation of thrombin in the context of either inflammation or putative inter-species molecular incompatibilities between activated coagulation factors and their natural anticoagulants. Relatively selective thrombin Inhibition with the serine protease inhibitor SDZ MTH 958 (MTH-958) are independent of heparinoids and anti-thrombin III. MTH-958 has been shown to significantly prolong porcine cardiac function during perfusion with human blood in an ex vivo model. The aim of this study was to validate the role of thrombin generation in a rodent model of discordant xenograft rejection in vivo. The effect of thrombin inhibition with MTH-958 was tested in both hyperacute rejection (HAR) and delayed xenograft rejection (DXR) after decomplementation with cobra venom factor (CVF) in normal Lewis (Lew) rats and Intrinsic C6 deficiency In PVG (C6-/PVG) recipient rats. Recipient rats received heterotopic guinea pig cardiac xenografts and were treated with titrated doses of MTH-958 until the time of graft rejection. Plasma samples at selected time points were examined to confirm effective thrombin inhibition, and rejected grafts were analyzed by immunohistology. MTH-958 significantly improved graft survival in HAR albeit the extent of prolongation was not marked, but the agent failed to prolong survival In CVF-treated Lew rats. In C6-/PVG rats receiving MTH-958, a significantly reduced graft survival time was observed when compared with C6-/PVG controls. The grafts from MTH-958-treated animals showed dense deposits of C3, IgM, and IgG with fibrin levels similar to controls. The thrombin antagonist tested could prolong xenograft survival during HAR but had no benefit in DXR. The relative non-specificity of the serine protease inhibitor MTH-958 with the potential activation of alternative pathway of complement via the inhibition of factor I could account for the failure to prolong xenograft survival in DXR. The pathogenetic significance of thrombin generation in this situation remains to be determined by the use of more selective and pharmacologically acceptable I anti-thrombin agents.     

Continuous venous infusion of doxorubicin in advanced sarcomas

Seventeen patients with advanced sarcoma were treated with continuous venous infusion of doxorubicin for a mean of 118 days, achieving total doses up to 1097 mg/m2. Three partial responses and one minor response were obtained. Major toxic effects were stomatitis and hand-foot syndrome. There was a low incidence of leukopenia (18%) and clinical cardiotoxicity (11%). Continuous venous infusion is a safe means of administering doxorubicin, with a response rate similar to that observed with bolus doxorubicin in metastatic sarcoma.     

Gastroduodenal tolerability of indomethacin and acetaminophen. A comparative endoscopic study in healthy subjects

The effect of a 5- and 10-day treatment with indometacin and acemetacin (Rantudil) on the gastroduodenal mucosa was endoscopically evaluated in 16 healthy volunteers. In a randomised double-blind cross-over fashion the volunteers received 50 mg t.i.d. indometacin as well as 60 mg t.i.d. acemetacin. Acemetacin evoked after 5 and 10 days significantly less gastroduodenal lesions than indometacin. Possible reasons for this apparently better tolerability of acemetacin in man are discussed.     

Malignant histiocytosis. Complete remission in two pediatric patients

The experience with the treatment of malignant histiocytosis has been disappointing. Despite modest treatment success with a combination of cyclophosphamide, Adriamycin (doxorubicin), vincristine and prednisone, the overall prognosis remains poor. There are only a few reports of prolonged complete remissions in pediatric patients. The following report describes two children who have had long-term remission with an aggressive combination chemotherapy program that included intrathecal prophylaxis. The chemotherapeutic regimen described merits further evaluation in a larger number of patients.     

High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain.

The mitochondrial theory of aging proposes that mitochondrial DNA (mtDNA) accumulates mutations with age, and that these mutations contribute to physiological decline in aging and degenerative diseases. Although a great deal of indirect evidence supports this hypothesis, the aggregate burden of mtDNA mutations, particularly point mutations, has not been systematically quantified in aging or neurodegenerative disorders. Therefore, we directly assessed the aggregate burden of brain mtDNA point mutations in 17 subjects with Alzheimer's disease (AD), 10 elderly control subjects and 14 younger control subjects, using a PCR-cloning-sequencing strategy. We found that brain mtDNA from elderly subjects had a higher aggregate burden of mutations than brain mtDNA from younger subjects. The average aggregate mutational burden in elderly subjects was 2 x 10(-4) mutations/bp. The bulk of these mutations were individually rare point mutations, 60% of which changed an amino acid. Control experiments ensure that these results were not due to artifacts arising from PCR error, mistaken identification of nuclear pseudogenes or ex vivo oxidation. Cytochrome oxidase activity correlated negatively with increasing mutational burden. These findings significantly bolster the mitochondrial theory of aging.     

Heat shock protein hsp72 induction in cortical and striatal astrocytes and neurons following infarction

Transient global and transient focal ischemia induced the 72 kDa heat shock protein (hsp72) in neurons in cortex, striatum, and other regions known to be injured during transient ischemia. A novel finding was the induction of hsp72 in islands (cylinders in three dimensions) of cells composed of astrocytes around the perimeter and neurons in the interior. Since histology showed pale staining in these regions, it is proposed that these islands represent areas of focal infarction in the distribution of small cortical and lenticulostriate arteries. Although the factors responsible for hsp72 induction during ischemia and infarction are unknown, these results suggest differences in mechanisms of hsp72 induction in astrocytes compared to neurons.