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.     

Jejunal gastrointestinal stromal tumor: a cause of obscure gastrointestinal bleeding

In cases of obscure gastrointestinal bleeding, when a source for blood loss is not apparent from examination of the colon and upper gastrointestinal tract, the small bowel usually becomes the focus of investigation. A tumor with interesting pathologic features was found in a patient who presented with recurrent episodes of massive obscure gastrointestinal hemorrhage. This case highlights the importance of considering small intestinal tumors as the likely cause of obscure gastrointestinal hemorrhage in young patients and how a noninvasive test, eg, abdominal computed tomography scan, might obviate the need for more invasive testing.     

Murein lipoprotein is a critical outer membrane component involved in Salmonella enterica serovar typhimurium systemic infection

Lipopolysaccharide (LPS) and Braun (murein) lipoprotein (Lpp) are major components of the outer membrane of gram-negative enteric bacteria that function as potent stimulators of inflammatory and immune responses. In a previous paper, we provided evidence that two functional copies of the lipoprotein gene (lppA and lppB) located on the chromosome of Salmonella enterica serovar Typhimurium contributed to bacterial virulence. In this study, we characterized lppA and lppB single-knockout (SKO) mutants and compared them with an lpp double-knockout (DKO) mutant using in vitro and in vivo models. Compared to the lpp DKO mutant, which was nonmotile, the motility of the lpp SKO mutants was significantly increased (73 to 77%), although the level of motility did not reach the level of wild-type (WT) S. enterica serovar Typhimurium. Likewise, the cytotoxicity was also significantly increased when T84 human intestinal epithelial cells and RAW264.7 murine macrophages were infected with the lpp SKO mutants compared to the cytotoxicity when cells were infected with the lpp DKO mutant. The level of interleukin-8 (IL-8) in polarized T84 cells infected with the lppB SKO mutant was significantly higher (two- to threefold higher), reaching the level in cells infected with WT S. enterica serovar Typhimurium, than the level in host cells infected with the lppA SKO mutant. The lpp DKO mutant induced minimal levels of IL-8. Similarly, sera from mice infected with the lppB SKO mutant contained 4.5- to 10-fold-higher levels of tumor necrosis factor-alpha and IL-6; the levels of these cytokines were 1.7- to 3.0-fold greater in the lppA SKO mutant-infected mice than in animals challenged with the lpp DKO mutant. The increased cytokine levels observed with the lppB SKO mutant in mice correlated with greater tissue damage in the livers and spleens of these mice than in the organs of animals infected with the lppA SKO and lpp DKO mutants. Moreover, the lppB SKO mutant-infected mice had increased susceptibility to death. Since the lpp DKO mutant retained intact LPS, we constructed an S. enterica serovar Typhimurium triple-knockout (TKO) mutant in which the lppA and lppB genes were deleted from an existing msbB mutant (msbB encodes an enzyme required for the acylation of lipid A). Compared to the lpp DKO and msbB SKO mutants, the lpp-msbB TKO mutant was unable to induce cytotoxicity and to produce cytokines and chemokines in vitro and in vivo. These studies provided the first evidence of the relative contributions of Lpp and lipid A acylation to Salmonella pathogenesis.     

Intraocular pressure profile during general anesthesia

The effect of some anesthetic drugs on intraocular pressure (IOP) was studied in 120 normal healthy patients undergoing non-ophthalmic surgical procedures. IOP rose significantly following the injection of succinylcholine (SCh) alone, or when such injection had been preceded by a pretreatment with a "self-taming" dose of SCh or d-tubocurarine (d-Tc). Though the rise in IOP after diazepam pretreatment was significant, the magnitude was lower than that observed in the groups pretreated with the other two agents. Halothane brought the IOP down faster and lower than ether. SCh is unsafe for intubation for the administration of general anesthesia in cases involving penetrating ocular injuries. It can, however, be used safely for routine ophthalmic surgery, providing that 8 minutes are allowed to elapse between injection and corneal or scleral incision. Halothane is preferred to ether, since the former lowers IOP faster and in a greater amount than the latter.     

Nutritional correlates of acute respiratory infections

During October 1992 to June 1993 in eight villages covered by the Primary Health Center Machhra in Meerut District, India, interviews with mothers and examinations of 1600 children aged less than 5 years (under-fives) were conducted to examine the relationship between acute respiratory infection (ARI) and malnutrition. 42.25% of all children had an ARI within the last 15 days. Most ARIs (73.4%) were considered mild (cough and cold with no pneumonia). Pneumonia accounted for 19.5% of all ARI cases, which were considered moderate. The remaining ARI cases were severe (severe and very severe pneumonia). 57.5% of all children suffered from protein energy malnutrition (PEM). 78.6% of children aged 12-14 months had PEM. ARI was more common among malnourished children than well-nourished children (52.2% vs. 28.8%; p 0.001). The incidence of ARI increased as the nutritional status deteriorated (p 0.05). It also increased as the midarm circumference decreased (p 0.001). These findings confirm the synergistic action between malnutrition and infection, in this case ARI. Malnourished children suffer considerable impairment in immunity, especially cellular immunity, which makes them more prone to ARI. These findings reinforce the need to strengthen the quality, quantity, and accessibility of nutritional services, particularly promotion of breast feeding and vitamin A supplementation.     

Mixed germ cell tumour of the pineal region: a case report

An intracranial mixed germ cell tumour with germinoma and teratoma components is reported. The patient presented with parinaud's syndrome and precocious puberty. The treatment involved partial surgical debulking followed by whole brain radiotherapy (4500 cGY in 25 fraction over 5 weeks) and chemotherapy (consisting of cisplatin and etoposide). Post treatment MRI showed no residual lesion. The controversies in the management are discussed.     

Relative bioavailabilities of natural and synthetic vitamin E formulations containing mixed tocopherols in human subjects

There are several reports in the literature on the relative bioavailabilities of RRR (natural) vs. all-rac (synthetic) forms of vitamin E in humans and animal models but none on the bioavailability of alpha-tocopherol in mixed vitamin E formulations. In the present study we examined the bioavailability of alpha-tocopherol in a typical commercially available product containing mixed tocopherols. We also tested a formulation containing all-rac-alpha-tocopherol with mixed tocopherols for purposes of comparison along with straight RRR- and all-rac-alpha-tocopheryl acetate as reference products. Normal male subjects were given one of the four formulations of vitamin E (800 IU per day in softgel capsule form for 10 days): 1. All-rac-alpha-tocopheryl acetate, 2. RRR-alpha-tocopheryl acetate, 3. RRR-alpha-tocopherol with mixed tocopherols, and 4. all-rac-alpha-tocopherol with mixed tocopherols. Both serum alpha- and gamma-tocopherols were determined by HPLC at baseline, and at days 2, 4, 7 and 10. The values for alpha- at baseline and 10 days were 0.80, 0.80, 0.80 & 0.79 mg/dl and 1.67, 1.72, 1.76 & 1.62 mg/dl. The values for gamma- were 0.28, 0.29, 0.30 & 0.29 mg/dl and 0.11, 0.08, 0.10 & 0.10 mg/dl. Thus the data show that a) the bioavailability of RRR- and all-rac-alpha-tocopherols is not affected by other tocopherols, and b) both RRR- and all-rac-alpha-tocopherol (free or esterified) significantly suppress the serum gamma tocopherol to the same extent. Furthermore, since there was no difference in the serum values of alpha-tocopherol between RRR- and all-rac-vitamin E given the same dose as IUs, the data also support the currently accepted ratio of 1.36 for the biopotency of RRR- vs. all-rac-alpha-tocopheryl acetate.