Antibody seronegative human T-lymphotropic virus type III (HTLV-III)- infected patients with acquired immunodeficiency syndrome or related disorders

The human T-lymphotropic virus type III (HTLV-III) is the primary cause of the acquired immunodeficiency syndrome (AIDS) and related disorders (ARC). Prior studies have reported that nearly all symptomatic patients with AIDS or ARC manifest antibody to HTLV-III. This observation has engendered efforts to screen for HTLV-III, especially prior to blood donation, with assays for antibody to HTLV-III. We report the first two cases, one with AIDS and one with ARC, that are HTLV-III virus positive but antibody negative. Accurate diagnosis of HTLV-III infection in some cases may require direct virus culture or tests for antigen. In addition, lack of HTLV-III antibody may indicate an atypical clinical course of AIDS.     

Properties of an in vitro bioassay for hypertrehalosemic hormone of Blaberus discoidalis cockroaches

The ability of the fat body to respond to the hypertrehalosemic action of corpora cardiaca-allata (CC + CA) extracts was measured in vitro with tissue from adult, male Blaberus discoidalis cockroaches. Only trehalose increased in the hemolymph when gland extracts were injected in vivo; likewise, only trehalose levels responded when fat bodies were exposed to gland extracts in vitro. Although fat bodies from 0-day-old animals gave the least response to gland extracts, all animals 5 or more days old showed elevated responses. A linear dose-response occurred between 0.02 and 0.08 CC + CA pair. Fat bodies did not show an in vitro, hypertrehalosemic response to insulin, glucagon, proctolin, dopamine, epinephrine, norepinephrine, serotonin, octopamine, or tyramine. A strong hypertrehalosemic response was found to both synthetic adipokinetic hormone and red-pigment concentrating hormone; however, reversed-phase, thin-layer chromatography of CC + CA extracts and adipokinetic hormone indicated that the hypertrehalosemic effect and the adipokinetic hormone were separate. This in vitro system comprises a relatively rapid, simple, and accurate bioassay for the hypertrehalosemic neurohormone of insects.     

Cardiac arrhythmias in patients with surgical repair of Ebstein's anomaly

Preoperative, perioperative and postoperative arrhythmias in 52 consecutive patients who underwent operation for Ebstein's anomaly were reviewed. There were 25 male and 27 female patients (mean age 18 years, range 11 months to 64 years). Thirty-four patients had one or more documented arrhythmias preoperatively (18 had paroxysmal supraventricular tachycardia, 10 had paroxysmal atrial fibrillation or flutter, 13 had ventricular arrhythmia and 3 had high grade atrioventricular block). Seven patients without documented arrhythmias had a history typical of tachyarrhythmias. During the perioperative and early postoperative periods, 14 patients had atrial tachyarrhythmias and 8 had ventricular tachycardia or ventricular fibrillation. There were seven deaths between day 1 and 27 months after operation. Five of these deaths were sudden (all in male patients, aged 12 to 34 years), and four of the patients had had perioperative ventricular tachycardia or ventricular fibrillation. One patient was taking one antiarrhythmic agent and another patient was taking two at the time of sudden death. Of the 18 patients with paroxysmal supraventricular tachycardia and 9 patients with paroxysmal atrial fibrillation or flutter preoperatively who were followed up for a mean of 40 and 36 months, respectively, 22 and 33% continued to have symptomatic tachycardia. Of the 11 patients (mean age 9 years) without preoperative documentation or symptoms of arrhythmia, follow-up data were obtained (range 1 to 144 months, mean 31) in 9 patients. None died suddenly or developed symptomatic arrhythmia.     

Techniques for high-resolution MR imaging of atherosclerotic plaque

Atherosclerotic cardiovascular disease is the most common cause of death in the United States. Investigation of atherosclerotic plaque morphology and composition is important because the findings may be useful in predicting prognosis or response to therapy. This study presents high-resolution magnetic resonance (MR) imaging techniques developed on a 1.5-T whole-body imager with a custom-built surface coil, for characterizing the composition and morphology of plaque removed at carotid endarterectomy. The initial comparison of MR imaging and histologic results showed good correlation. In conjunction with MR angiography, these techniques could be used in in vivo imaging to define the size, location, and contents of atherosclerotic plaque at the carotid bifurcation.     

Effects of injury severity on regional and temporal mRNA expression levels of calpains and caspases after traumatic brain injury in rats

Despite a preponderance of studies demonstrating gene expression and/or enzymatic activation of calpain and caspase proteases after traumatic brain injury (TBI), no studies have examined the effects of injury magnitude on expression levels of these cell death effectors after TBI. Determination of the degree to which injury severity affects specific expression profiles is critical to understanding the relevant pathways contributing to post-trauma pathology and for developing targeted therapeutics. This investigation tested the hypothesis that different injury magnitudes (1.0, 1.2, and 1.6 mm) cause alterations in the regional and temporal patterns of mRNA expression of calpain-related (calpain-1 and -2, calpastatin) and caspase-related (caspases -3, -8, -9, BID) gene products after cortical impact in rats. Quantitative RT-PCR was used to compare effects of injury severity on mRNA levels in ipsilateral (injured) cortex and hippocampus, 6 h to 5 days post-injury. TBI caused increases in mRNA expression of all proteins examined, with the highest expression detected in the cortex. Generally, injury magnitude and levels of gene expression were positively correlated. High levels of gene induction were observed with BID, caspase-3, and -8, while caspase-9 mRNA had the lowest level of induction. Interestingly, although calpains are activated within minutes of TBI, calpain mRNA expression was highest 72 h to 5 days post-TBI. This study is the first analysis of the regional and temporal expression of calpains and caspases after TBI. These data provide insight into the inter-relationship of these two protease families and on the distinct but overlapping cascades of cell death after TBI.     

Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Study Type – Therapy (cohort) Level of Evidence 4 What's known on the subject? and What does the study add? Accumulating evidence suggests that inflammation may contribute to the development of BPH and LUTS. Therefore, it is plausible that anti‐inflammatory agents, such as aspirin and other NSAIDs, may reduce the risk of BPH/LUTS, as was observed in a recent analysis of daily aspirin use and BPH/LUTS risk in the Olmsted County Study of Urinary Symptoms and Health Status in Men. The present study, conducted in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, found no association for recent aspirin or ibuprofen use with the risk of BPH/LUTS.

OBJECTIVE

• ? To investigate the relationship between non‐steroidal anti‐inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)‐related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development.

PATIENTS AND METHODS

• ? At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate‐specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n= 4771).
• ? During follow‐up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006–2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia.
• ? Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self‐reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥30 mL on any follow‐up DRE) and elevation in PSA level (>1.4 ng/mL on any follow‐up PSA test).

RESULTS

• ? Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92–1.21, P= 0.043–0.91) and frequency of use (risk ratios for one category increase in NSAID use = 0.98–1.11, P‐trends = 0.10–0.99) with incident BPH/LUTS.

CONCLUSION

• ? The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development.

     

Successful implementation of new osteopathic graduate medical education programs in a community hospital: challenges and lessons learned

Development of new osteopathic graduate medical education (OGME) programs has emerged as a priority for the osteopathic medical profession. As colleges of osteopathic medicine (COMs) expand class sizes and branch campuses, and as new COMs are launched, availability of sufficient internship, residency, and fellowship positions for future COM graduates will become a challenge. Because of constraints in graduate medical education reimbursement, growth of existing training programs is limited. For hospitals that did not sponsor internship and residency programs before January 1, 1995, the Centers for Medicare and Medicaid Services offers an exception to funding restraints on expansion of training programs. However, successful development and implementation of new OGME programs remains a formidable undertaking. Moreover, because of idiosyncrasies of medical education reimbursement, successful recruitment of COM graduates into new training positions is paramount to ensure program viability. The authors describe lessons learned from the successful implementation of new OGME programs in a community hospital, and they offer recommendations for other hospitals considering such an endeavor.     

The Effects of Serum from Patients with Acute Liver Failure on the Growth and Metabolism of Hep G2 Cells

In many bioartificial liver systems currently being designed and evaluated for use in fulminant hepatic failure, direct contact is required between the patient's blood and the liver cells in the device. The efficacy of such devices will be influenced by the interaction of fulminant hepatic failure (FHF) patient serum with the cells. We have found that FHF serum inhibits the growth rate and the synthesis of DNA, RNA, and protein; disturbs glutathione homeostasis; and induces morphological changes in cultured human Hep G2 cells. These interactions should influence the design of bioartificial liver devices based on proliferating cell lines and indicate the requirement to pretreat FHF patient plasma to reduce the toxin load.     

Deep dermal burn injury results in scarless wound healing in the ovine fetus

Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66 degrees C for 7 seconds, and at 82 degrees C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of alpha-smooth muscle actin and transforming growth factor-beta1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury.