In utero bone marrow transplantation of fetal baboons with mismatched adult marrow: initial observations

Recent advances in prenatal diagnoses of sickle cell anemia and thalassemia permit early identification of affected fetuses. However, the only intervention possible to date is abortion of the affected fetuses. Transplantation of normal marrow into fetuses in utero could correct these life-threatening disorders, but to accomplish this techniques must be developed for fetal transplantation in man. Therefore, we have transplanted fetal baboons with mismatched adult baboon bone marrow from donors that differed at the glucose phosphate isomerase locus. Twenty-two fetuses between 60 and 160 days of gestation (term gestation is 182 days) were transplanted intraperitoneally with 10(9) marrow mononuclear cells/kg body weight using an ultrasonic technique. No immunosuppressive or preparative regimen was given prior to or after transplantation, and all fetuses tolerated the procedure well. One month after transplantation fetal blood samples were obtained to assess chimerism. Three chimeras were detected among 10 fetuses transplanted at 80 days' gestation, and no chimeras were detected in fetuses greater than 80 days' gestation at the time of transplantation. All chimeras died in utero during the third trimester of pregnancy: one of an intrauterine infection at 160 days' gestation, one at 135 days' gestation and one at 145 days' gestation. In contrast, the other 19 non-chimeric fetuses survived. These data suggest: (1) in utero fetal bone marrow transplantation is technically feasible in primates; (2) that allogeneic adult bone marrow can engraft and persist for at least 1 month in fetal baboons transplanted at 80 days of gestation; and (3) that delineation of the causes for loss of fetal chimeras should prove valuable in assessing the therapeutic potential for in utero bone marrow transplantation in man.     

Magnetic resonance imaging of autologous fat grafting

A 30-year-old female patient with isolated facial lipodystrophy underwent two sessions of fat injection. MR signals of injected fat at different injection ages were compared to native fat. Native T1 signal was smaller for transplant fat, probably due to a slightly lower fat content and/or fibrosis or due to higher perfusion. T2 signal of transplants was significantly higher than that of native fat. T1 post-contrast was also higher, and contrast uptake of transplanted fat increased slightly with transplant age, which could be explained by an increasing perfusion. This study demonstrates the differences and MR signal time changes of native and transplanted fat.     

Virucidal activities of medium- and long-chain fatty alcohols, fatty acids and monoglycerides against herpes simplex virus types 1 and 2: comparison at different pH levels

Previous studies have shown that certain lipids and fatty alcohols have microbicidal activities against a number of pathogens. In this study, virucidal activities of fatty alcohols and lipids were tested against HSV types 1 and 2 at various concentrations, times, and pH levels. The aim was first, to determine which compounds are most virucidal against HSV and could possibly be used as active ingredients in topical drug formulations and second, to attempt to throw light on the mode of action of virucidal lipids. Good agreement was found between the activities for HSV-1 and HSV-2. The activity of a compound depends on the concentration and time of contact and most of the compounds are more active at pH 4.2 than at pH 7. This information may be helpful in the formulation of pharmaceutical dosage forms for treatment of herpes lesions in skin and mucosa. The difference between the polar groups of alcohols and fatty acids, i.e. hydroxyl group versus carboxyl group, and the corresponding difference in their hydrophile-lipophile balance (HLB) may explain their different virucidal activities against HSV. However, in most cases HLB numbers cannot explain the different virucidal activities of fatty alcohols and lipids, particularly not their increased activity at low pH. It is more likely that the acidic environment makes HSV more sensitive, possibly by ionic changes in the envelope proteins.     

Minimal invasive endoscopic resection of a giant left atrial appendage aneurysm

We report a case of a 35-year-old male patient who presented with chronic atrial fibrillation secondary to a massive congenital left atrial appendage aneurysm. Minimal invasive endoscopic resection of the left atrial aneurysm with cryoablation was performed. The patient was discharged home in sinus rhythm.     

Importance of adrenal incidentaloma in patients with a history of malignancy

BACKGROUND: Adrenal incidentaloma presents a frequent finding in patients with a history of malignancy. This study was carried out to determine whether imaging techniques can discriminate between a malignant and a benign adrenal tumor and subsequently select candidates for adrenal surgery. METHODS: Beginning in July 1995, oncologic patients with adrenal incidentaloma underwent abdominal ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and [ 18 ]fluoro-2-deoxy-D-glucose positron emission tomography (18-FDG-PET). Consecutively in all patients adrenalectomy was performed. Histologic findings were compared with the imaging results. RESULTS: In 42 patients, 33 to 79 years old (mean age, 58 years), 44 adrenal lesions were detectable. Two patients presented with bilateral adrenal masses. At operation, 43 adrenal resections and 3 biopsies were performed. Histologic examination revealed 31 metastases (71%) and 13 adrenal adenomas (29%). In metastases the sensitivity of ultrasonography, CT, MRI, and 18-FDG-PET was 66%, 81%, 100%, and 100%, respectively. For adrenal adenoma, the sensitivity of ultrasonography, CT, MRI, and 18-FDG-PET was 46%, 39%, 100%, and 54%, respectively. CONCLUSIONS: In oncologic patients with indeterminate adrenal tumors MRI and 18-FDG-PET provide accurate differentiation between metastases and benign adenomas. Positive results of these 2 imaging modalities are highly suggestive for metastatic disease. In cases of negative MRI and 18-FDG-PET results the adrenal lesion corresponds to a benign adenoma that needs no surgical intervention.     

Increased platelet activation in young Zucker rats with impaired glucose tolerance is improved by acarbose

Patients with diabetes display increased platelet activation. Recent data show a markedly increased risk for cardiovascular events already in pre-diabetic individuals with impaired glucose tolerance (IGT). We investigated whether IGT is associated with platelet activation. Blood samples were collected from young lean (control) and obese Zucker rats, an established model of IGT, after single oral application of sucrose (4 g.kg-1). Platelet-bound fibrinogen and platelet surface-expression of P-selectin were assessed as indices of platelet activation using flow cytometry. In lean Zucker rats, acute sucrose application induced fibrinogen-binding and P-selectin surface-expression, which was prevented by co-administration of acarbose (10 mg.kg-1). In obese Zucker rats, platelet activation was already maximally increased under baseline conditions with no significant increase after sucrose application. Chronic treatment with acarbose (15 mg.kg-1.day-1) significantly reduced platelet activation in these animals. Acute ingestion of sucrose induces platelet activation which is prevented by acarbose. IGT is associated with marked platelet activation that can be reduced by chronic administration of acarbose. The positive modulation of platelet activation by acarbose may contribute to the reduction of cardiovascular events in patients with IGT.     

Electrical stimulation in the treatment of pelvic pain due to levator ani spasm

OBJECTIVE: To evaluate experience with intravaginal electrical stimulation for the relief of pain when used as adjunctive therapy in women with chronic pelvic pain and levator ani spasm. STUDY DESIGN: A retrospective cohort of consecutively treated patients from 1999 and 2000 was identified using billing records. Systematic chart review was completed using standardized data collection forms for all patients receiving electrical stimulation for pain from levator ani spasm. Data collected were objective for major variables and subjective for outcomes. Demographic data were reported as means and standard deviations. Stimulation characteristics were compared using ANOVA. Survival analysis was performed using life table methods. RESULTS: Medical records from 66 consecutive patients treated during an 18-month interval were reviewed. Demographic characteristics included mean age of 38.7 years, 13 years of education and parity of 2. Married women composed 75% of the study group, with 81% white, 10% Hispanic and 9% black. Of the 66 patients studied, 50 had follow-up documentation with an average duration of 14.5 weeks. Overall, 34 patients (52%) demonstrated improvement in pelvic pain following vaginal electrical stimulation. Using survival analysis, 51% of patients had persistent improvement 30 weeks after treatment. There were no differences in age, race, education or parity between patients reporting a sustained benefit of stimulation and those not reporting a benefit. CONCLUSION: Vaginal electrical stimulation may help a selected population of women with pelvic pain due to levator ani spasm.     

Small colony variants of Staphylococcus aureus and pacemaker-related infection

We describe the first known case of a device-related bloodstream infection caused by Staphylococcus aureus small colony variants. Recurrent pacemaker-related bloodstream infection within a 7-month period illustrates the poor clinical and microbiologic response to prolonged antimicrobial therapy in a patient infected with this S. aureus subpopulation.Infections caused by Staphylococcus aureus range from mild skin infections to acute life-threatening diseases such as pneumonia, osteomyelitis, and endocarditis. However, S. aureus may also cause a chronic disease with persistent and recurrent infections. Skin and soft tissue infections, chronic osteomyelitis, and persistent infections in patients with cystic fibrosis have been associated with small colony variants, a naturally occurring subpopulation of the species S. aureus (1–6). S. aureus small colony variants are characterized as electron transport deficient bacteria because of their auxotrophism to hemin or menadione or are recognized as thymidine-dependent. These variants produce very small, mostly nonpigmented and nonhemolytic colonies. In addition, they also demonstrate various other features that are atypical for S. aureus, including reduced coagulase production, failure to use mannitol, and increased resistance to aminoglycosides and cell-wall active antibiotics (3–10). Furthermore, the ability of these variants to persist intracellularly within nonprofessional phagocytes has been described (3,5,11). Because of their fastidious growth characteristics and unusual morphologic appearance, small colony variants present a challenge both to the microbiologist and the clinician, often resulting in misidentification and misinterpretation (1,2,7,8). Prerequisite for recovering and identifying these variants is the application of extended conventional culture and identification techniques (3,5,8). We report the first case of a pacemaker-related bloodstream infection caused by S. aureus small colony variants. This case illustrates the poor clinical and microbiologic response to prolonged antimicrobial therapy in patients infected with these variants.