Endotoxic activity of cell-free rumen fluid from cattle fed hay or grain

The cell-free rumen fluid from cattle fed hay or grain exhibited the following biological characteristics which strongly suggest the presence of endotoxin or a toxic principle similar to endotoxin of gram-negative bacteria: proved lethal to mice when injected with actinomycin D; proved extremely lethal to chick embryo; induced biphasic pyogenic response in rabbits; enhanced susceptibility to bacterial infection in mice; evoked positive epinephrine skin reaction in rabbits and phenol-water or aqueous ether proved lethal to mice and chick embryos. A quantitative difference in concentrations of endotoxin was observed on LD50 in mice and chick embryos and response to the epinephrine skin test in rabbits. Cell-free rumen fluid of grain-fed cattle contained at least twice as much endotoxin as that of hay-fed cattle. Endotoxin in cell-free rumen fluid and in higher concentration in cattle fed grain than in those fed hay support the hypothesis that rumen bacterial endotoxins may participate in the pathogenesis of diseases associated with high grain feeding such as lactic acidosis and the sudden-death syndrome.     

Massive hemorrhage caused by a perforating Gianturco-Z stent resulting in an aortoesophageal fistula

Squamous cell carcinoma of the tonsil has a relatively poor prognosis. Aggressive surgery, radiation therapy and combinations of irradiation and surgery have been employed but there exists some controversy about the efficacy of these treatment modalities. The purpose of this paper is to compare the efficacy of treatment between the surgery followed by radiation therapy and the preoperative radiation therapy followed by surgical resection. The medical records of 33 patients treated for squamous cell carcinoma of the tonsil at the Department of Otolaryngology-Head and Neck Surgery, Korea University Hospital between 1989-1993 were reviewed retrospectively. None of the patients were stage I, but stage II, III, and IV were four, five, and 24 patients, respectively. There were 30 males and three females. The most common histopathology was moderately differentiated squamous cell carcinoma (20/33). The 13 patients treated initially with surgery had an overall three-year survival rate of 38.5%, and the rate for the 20 patients treated initially with radiation was 40%. The main pattern of treatment failure was a local recurrence and neck metastases, and pathologic differentiation thought to be an important prognostic factor. Complications are fewer in patients treated initially with surgery (23.1%) than patients initially treated with radiation (50.0%). There is no difference in the efficacy between the two therapeutic groups.     

Glutathione modulates ryanodine receptor from skeletal muscle sarcoplasmic reticulum. Evidence for redox regulation of the Ca2+ release mechanism

In this report, we demonstrate the ability of the cellular thiol glutathione to modulate the ryanodine receptor from skeletal muscle sarcoplasmic reticulum. Reduced glutathione (GSH) inhibited Ca2+-stimulated [3H]ryanodine binding to the sarcoplasmic reticulum and inhibited the single-channel gating activity of the reconstituted Ca2+ release channel. The effects of GSH on both the [3H]ryanodine binding and single-channel measurements were dose-dependent, exhibiting an IC50 of approximately 2.4 mM in binding experiments. Scatchard analysis demonstrated that GSH decreased the binding affinity of ryanodine for its receptor (increased Kd) and lowered the maximal binding occupancy (Bmax). In addition, GSH did not modify the Ca2+ dependence of [3H]ryanodine binding. In single-channel experiments, GSH (5-10 mM), added to the cis side of the bilayer lipid membrane, lowered the open probability (Po) of a Ca2+ (50 microM)-stimulated Ca2+ channel without modifying the single-channel conductance. Subsequent perfusion of the cis chamber with an identical buffer, containing 50 microM Ca2+ without GSH, re-established Ca2+-stimulated channel gating. GSH did not inhibit channel activity when added to the trans side of the bilayer lipid membrane. Similar to GSH, the thiol-reducing agents dithiothreitol and beta-mercaptoethanol also inhibited high affinity [3H]ryanodine binding to sarcoplasmic reticulum membranes. In contrast to GSH, glutathione disulfide (GSSG) was a potent stimulator of high affinity [3H]ryanodine binding and it also stimulated the activity of the reconstituted single Ca2+ release channel. These results provide direct evidence that glutathione interacts with reactive thiols associated with the Ca2+ release channel/ryanodine receptor complex, which are located on the cytoplasmic face of the SR, and support previous observations (Liu, G, Abramson, J. J., Zable, A. C., and Pessah, I. N. (1994) Mol. Pharmacol. 45, 189-200) that reactive thiols may be involved in the gating of the Ca2+ release channel.     

PCR-restriction fragment length polymorphism (RFLP) analyses reveal both extensive clonality and local genetic differences in Candida albicans

Using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to obtain genotypes for the diploid pathogenic yeast, Candida albicans, we analysed 204 C. albicans isolates from three populations of the Duke University community: two from clinical sources [one from patients infected with human immunodeficiency virus (HIV) and the other from patients without HIV infection], and the third from healthy student volunteers. The results indicated: (i) extensive evidence for clonality within and between populations of C. albicans; and (ii) greater genotypic and gene diversities in the nonclinical population than those derived from clinical specimens, regardless of HIV status. The two clinical populations were genetically more similar to each other than either was to the population consisting of isolates from healthy people. Within each population sample there was a general lack of heterozygotes, and random associations of alleles within and between loci were found in less than 50% of the loci or pairs of loci. These findings were consistent between the two sets of samples analysed: those including all isolates and those including only clone-corrected isolates. Possible mechanisms are presented to explain the observed patterns of genetic variation within and between C. albicans populations.     

A case of fatal pulmonary thromboembolism associated with the use of intravenous estrogen therapy

OBJECTIVE: To report a case of fatal pulmonary embolism associated with the use of i.v. estrogen therapy for menometrorrhagia. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 52-year-old woman with fibroid uterus treated with GnRH analogues with add-back therapy who presented with excessive vaginal bleeding. INTERVENTION(S): Intravenous conjugated estrogens were administered for a total of six doses. MAIN OUTCOME MEASURE(S): Fatal thromboembolic event. RESULT(S): The day after i.v. conjugated estrogens were administered, the patient had only scant vaginal bleeding, but she experienced the sudden onset of respiratory distress, became comatose, and subsequently had ventricular fibrillation leading to asystole. All resuscitative efforts failed. Postmortem examination revealed bilateral pulmonary artery thromboembolism (saddle embolus). CONCLUSION(S): Intravenous conjugated estrogen therapy may be complicated by fatal thromboembolic events. This potential adverse effect must be considered in the use of such therapy for severe menometrorrhagia, especially when treating a patient at increased risk.     

Sonographic findings in testicular sarcoidosis simulating malignant nodule

Testicular involvement by sarcoidosis is rare. We report a case of a patient with known sarcoid who had a unilateral testicular nodule with apparent capsular invasion on sonography. The epididymis was normal on both sides. Despite these atypical features, pathology showed the nodule to be a sarcoid granuloma. In patients with sarcoidosis, the differential diagnosis of an intratesticular mass should include testicular involvement by sarcoid.     

Continuous purification of porcine lipase by rotating annular size-exclusion chromatography

Non-accidental head injury, be it shaking, impact(s) or a combination of the two, is characterised by subdural and/or subarachnoid haemorrhages with retinal haemorrhages, but minimal or absent external cranio-facial trauma. The classical assault scenario depicts the infant being gripped around the head, face, chest and abdomen and shaken or being gripped by a limb and swung. This gripping might be expected to leave physical evidence in the form of bruising. A study was undertaken to establish the prevalence, distribution and pathological association of external bruising in 24 cases of fatal non-accidental head injury in children. At autopsy, 17 cases had new external bruises, 15 old external bruises and 13, a combination of both. However, seven (29%) cases showed no fresh external bruising and five (21%) showed no external bruising at all. Thus, external bruising may be absent in children with fatal intracranial injury. The face was shown to be the commonest site of bruising followed by the forehead and buttocks. Limb, chest and abdominal bruising were found to be uncommon. Retinal haemorrhages were confirmed in 23 (96%) cases. It is hypothesised that bruising, when present, may be a result of abuse in the form of punches and slaps rather than due to gripping during the assault. We discuss why gripping does not necessarily result in external bruising.