Ureaplasma urealyticum intrauterine infection: role in prematurity and disease in newborns.

Ureaplasma urealyticum, a common commensal of the urogenital tract of sexually mature humans, is gaining recognition as an important opportunistic pathogen during pregnancy. While its etiologic significance in many aspects of adverse pregnancy remains controversial, recent evidence indicates that U. urealyticum in the absence of other organisms is a cause of chorioamnionitis. Furthermore, ureaplasmal infection of the chorioamnion is significantly associated with premature spontaneous labor and delivery. In at least some cases, it appears to be causal. Present evidence indicates that U. urealyticum is a cause of septicemia, meningitis, and pneumonia in newborn infants, particularly those born prematurely. There is strong but not definitive evidence that ureaplasmal infection of the lower respiratory tract can lead to development of chronic lung disease in very low-birth-weight infants. Although risk factors for colonization of the lower genitourinary tract have been identified, little information is available concerning risk factors for intrauterine infection and host immune responses to invasive infection. Recent establishment of animal models of respiratory and central nervous system diseases should provide an opportunity to evaluate risk factors, pathogenic mechanisms, and operative immune mechanisms. However, the most critical need is additional information concerning indications for diagnosis and treatment as well as efficacy of treatment.     

Monoclonal antibodies to human secretory "pregnancy-associated endometrial alpha 1-globulin," an insulin-like growth factor binding protein: characterization and use in radioimmunoassay, Western blots, and immunohistochemistry

Monoclonal antibodies were raised against pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG), a 32 KD insulin-like growth factor binding protein (IGF-BP), which represents a major secretory product of the human decidualized endometrium during pregnancy. This class of IGF-BP has been implicated in the modulation of action, inhibitory and stimulatory, of insulin-like growth factors. Immunization with the protein purified from pregnancy endometrium resulted after myeloma fusion in the isolation of six hybridoma clones and the antibodies produced were characterized. The Ka of the antibodies ranged between 4.75 x 10(9) M-1 and 0.7 x 10(8) M-1. In Western blots all monoclonal antibodies reacted with purified protein of molecular weight 32 KD and specifically detected this IGF-BP species in culture medium and cytosolic extracts of pregnancy endometrium and amniotic fluid. The monoclonal antibodies appear to define three epitope-bearing regions as evidenced by their reactivity to polypeptide fragments of the protein. After synthesis and secretion by tissue explants in vitro the protein is susceptible to cleavage into fragments possessing different monoclonal antibody-defined reactivity. Employing immunohistochemical techniques the protein was principally localized to decidual cells in tissue sections of pregnancy endometrium and solely to these cells after enzymic digestion of the tissue. The implications of these results are discussed with respect to potential role of IGF-BP in the action of IGF upon the IGF-1 receptor-bearing populations, including lymphocytes and trophoblast cells, D in the decidua.     

Malignancy may adversely influence the quality and behaviour of oocytes

A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age- matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.      

Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition

Background  

The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease.     

Binding proteins for insulin-like growth factors in the human ovary: identification, follicular fluid levels and immunohistological localization of the 29-32 kd type 1 binding protein, IGF-bp1.

The occurrence of pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG), a 29-32 kd insulin-like growth factor binding protein, now termed type 1 or IGF-bp1, has been examined in the human ovary by monoclonal and polyclonal antibody based radioimmunoassay and immunohistological techniques. Follicular fluids aspirated from 51 follicles of 32 women undergoing hyperstimulation involving buserelin or clomiphene-based protocols contained 35.5-276.0 ng/ml (mean 101.0 mg/ml) of immunoreactive IGF-bp1. Mean fluid concentrations were three times the level of IGF-bp1 detected in paired serum samples, available for 21 women. Immunoreactive IGF-bp1 in follicular fluid exhibited similar dose-response curves to purified protein and amniotic fluid and immunoreactive IGF-bp1 coeluted in gel filtration with a peak of [125I]-IGF-1 binding corresponding to the elution profile of purified IGF-bp1. Gel filtration also revealed the presence in follicular fluid of a greater than 100 kd binding protein with a binding capacity equal to IGF-bp1 under the conditions employed. A highly significant correlation (P less than 0.001) was found between follicular fluid progesterone and IGF-bp1 and a correlation of lower significance was found between oestradiol and IGF-bp1 (P less than 0.05). However, only low levels of immunoreactive IGF-bp1 were detected in supernatant media of granulosa cells in culture (range undetectable to 2.3 ng/ml). Employing monoclonal antibody-based immunohistology, immunoreactive IGF-bp1 was consistently associated with luteinized granulosa cells of corpora lutea rather than paraluteal cells and its intensity of reactivity appeared to reflect luteal phase steroid hormone profiles. No consistent reactivity was detected in preovulatory follicles and granulosa cells in culture, although reactivity was associated with primordial oocytes. Immunoreactive IGF-bp1 was detected in six of nine supernatant media of explants of luteal tissue obtained from five corpora lutea, with levels ranging from undetectable to greater than 200 ng/ml. These observations suggest that IGF-bp1 is primarily related to luteinization of the granulosa and the resultant luteal cells, and if produced by the luteal cells, additional exogenous factors are required to induce production by granulosa cells in vitro.     

In vitro activities of cefepime versus cefotaxime and ceftriaxone against penicillin-resistant Streptococcus pneumoniae determined by Etest

The Etest was used for determining in vitro susceptibilities of 144 unique clinical isolates of penicillin-intermediate and resistant Streptococcus pneumoniae to cefepime, cefotaxime, and ceftriaxone. MIC ranges were 0.12-8 mug/ml for cefepime and 0.06-16 mug/ml for cefotaxime and ceftriaxone. MICs for 50% of the isolates for the three agents were equivalent at 1 mug/ml, whereas MICs for 90% of the isolates were 2 mug/ml for cefotaxime and ceftriaxone, versus 4 mug/ml for cefepime. The Etest is a practical means for determining susceptibilities of S. pneumoniae to cefepime and other cephalosporins in diagnostic laboratories.     

Endotoxin-induced suppression of erythropoiesis: the role of erythropoietin and a heme synthesis stimulating factor

The regulation of erythropoiesis is primarily controlled by erythropoietin (Ep). Recently, however, other factors that both stimulate and inhibit erythropoiesis have been reported. Using an in vitro liquid culture of bone marrow cells, a factor in normal mouse serum was demonstrated that markedly stimulated heme synthesis by marrow erythroid cells. In this study, the role of this heme synthesis stimulating factor (HSF) and Ep in the erythropoietic suppression caused by endotoxin administration to mice was examined. Although HSF levels did not alter appreciably after endotoxin injection, marrow erythroid cells from these animals became unresponsive to the factor. This could be reversed if Ep was added to the culture in vitro or if the hormone was injected into the mice 18 hr prior to harvesting the marrow. This marrow erythroid cell response is identical to that seen in animals in whom Ep levels are markedly reduced, such as that found in exhypoxic polycythemia, and suggest a decrease in the hormone following endotoxin administration. Additional studies demonstrated that when Ep was injected into mice 6 hr after endotoxin administration, an increase in femoral erythroid colony-forming units (CFU-E), proerythroblast number, and 59 Fe incorporation into femoral marrow cells could be demonstrated. These findings, together with the marrow erythroid cell response to the hormone, suggest that the mechanism for suppression of erythropoiesis after endotoxin injection is a reduction in the level of circulating Ep.     

Macrolide-Resistant Mycoplasma pneumoniae,United States

Macrolide-resistant Mycoplasma pneumoniae (MRMP) is highly prevalent in Asia and is now being reported from Europe. Few data on MRMP are available in the United States. Using genotypic and phenotypic methods, we detected high-level MRMP in 13.2% of 91 M. pneumoniae­–positive specimens from 6 US locations.     

Evaluation of 3 Methods of Bladder Irrigation to Treat Bacteriuria in Persons With Neurogenic Bladder

Abstract

Background/Objective: We conducted a randomized, double-blind comparison of twice daily bladder irrigation using 1 of 3 different solutions in community-residing persons with neurogenic bladder who used indwelling catheters to evaluate efficacy in treatment of bacteriuria.

Methods: Eighty-nine persons with bacteriuria were randomized to irrigate their bladders twice daily for 8 weeks with 30 mL of (a) sterile saline, (b) acetic acid, or (c) neomycin-polymyxin solution. Urinalysis, cultures, and antimicrobial susceptibility tests were performed at baseline and weeks 2, 4, and 8 to determine the extent to which each of the solutions affected numbers and types of bacteria, urinary pH, urinary leukocytes, and generation of antimicrobial-resistant organisms.

Results: Bladder irrigation was well tolerated with the exception of 3 participants who had bladder spasms. None of the 3 irrigants had a detectable effect on the degree of bacteriuria or pyuria in 52 persons who completed the study protocol. A significant increase in urinary pH occurred in all 3 groups. No significant development of resistance to oral antimicrobials beyond what was observed at baseline was detected.

Conclusions: Bladder irrigation was generally well tolerated for 8 weeks. No advantages were detected for neomycin-polymyxin or acetic acid over saline in terms of reducing the urinary bacterial load and inflammation. We cannot recommend bladder irrigation as a means of treatment for bacteriuria in persons with neurogenic bladder.