Pulmonary Congestion by Lung Ultrasound in Ambulatory Patients With Heart Failure With Reduced or Preserved Ejection Fraction and Hypertension

Background

Although pulmonary congestion can be quantified in heart failure (HF) by means of lung ultrasonography (LUS), little is known about LUS findings (B-lines) in different HF phenotypes. This prospective cohort study investigated the prevalence and clinical and echocardiographic correlates of B-lines in ambulatory HF patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction compared with hypertensive patients. We related LUS findings to 12-month HF hospitalizations and all-cause mortality.

Effect of leuprolide acetate in patients with moderate to severe functional bowel disease

Moderate to severe functional bowel disease results in debilitating abdominal pain, nausea, intermittent vomiting, early satiety, bloating, abdominal distension, and/or altered bowel habits. Because it occurs 20–30 times more frequently in women than in men and its symptoms often coincide with the menstrual cycle, we hypothesized that reproductive steroids may antagonize diseased nerves of the gastrointestinal tract, enhancing the expression of symptoms. No effective or consistent therapy has existed for these patients. We prospectively investigated the effect of a gonadotropin-releasing hormone analog, leuprolide acetate, in 30 women with symptoms of moderate to severe functional bowel disease. The study was phase II, randomized, double blind, and placebo controlled. Lupron Depot 3.75 mg (which delivers a continuous low dose of drug for one month) or placebo were given intramuscularly monthly for three months. Symptom scores were assessed at each four-week visit. Follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone levels were assessed before and after therapy. Patients treated with low-dose leuprolide improved progressively and significantly in scores for nausea, vomiting, bloating, abdominal pain, and early satiety, and for overall symptoms (P<0.01–0.05). All hormone levels decreased significantly (P<0.05) except luteinizing hormone (P=0.054).This material was published in abstract form inGastroenterology 104:A548, and presented at the annual meeting of the American Gastroenterological Association, Boston, Massachusetts, May 15–21, 1993.This study was supported by a grant from TAP Pharmaceuticals Inc., Deerfield, Illinois.     

Negative associations of chronic stress and cognitive performance in older adult spouse caregivers

Despite research on psychosocial and physical correlates of caregiving, associations of caregiving with cognitive functioning have rarely been studied. We compared the cognitive functioning of 44 spouse caregivers of persons with Alzheimer's disease to 66 demographically-similar non-caregiver spouses; and, whether such differences are explained by demographic variables and distress. We observed that variance in Digit Symbol scores was explained by age [F(1,108)=26.80, p<.001, R(2)=.20] and education [DeltaF(1,107)=5.33, p=.023, DeltaR(2)=.04], and caregiver status [DeltaF(1,106)=4.57, p<.035, DeltaR(2)=.03]. However, when Distress (a composite of Uplifts, Burden, and Sleep Problems) was added to the equation, the lower level of cognitive functioning in caregivers was no longer significant (beta declined from.18 to.06), but distress was significant (beta=-.30). These results may have implications for caregiver adherence and may have relevance to the complex tasks caregivers must perform for care-recipients and the information they report to health care workers/researchers about their care-recipients.     

Clinical effectiveness of noncontact, low-frequency, nonthermal ultrasound in burn care

Most burns are thermal and can be treated on an outpatient basis with conventional care that includes daily dressing changes, debridement, and infection control. These treatments can exacerbate pain associated with burns. Noncontact, low-frequency, nonthermal ultrasound therapy is delivered via sterile saline mist and has been used to cleanse and debride a variety of acute and chronic wounds, including burns, with less associated pain. This case series study evaluated low-frequency, nonthermal ultrasound therapy as an adjunct to conventional burn care in six nonrandomly selected outpatients with partial- to full-thickness thermal burns. The effectiveness of low-frequency, nonthermal ultrasound was assessed through changes in wound bed composition, exudate characteristics, and pain. Patients rated pain using a 10-point numerical rating scale (0 = no pain; 10 = extreme pain). Noncontact ultrasound treatments of 3 to 20 minutes (depending on wound size) were administered up to five times weekly. Conventional treatments included antibacterial ointments and nonadherent moist dressings. Treatment continued until wounds were predominately granulation tissue. As few as one noncontact ultrasound treatment caused slough to lift easily and granulation tissue to develop quickly. Pain rapidly resolved and all wounds healed and closed without surgical intervention. In this case series study, noncontact ultrasound treatment was an effective adjunct to conventional burn care.     

Silencing of the maternally imprinted tumor suppressor ARHI contributes to follicular thyroid carcinogenesis

The two most common subtypes of thyroid cancer, follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma, have been extensively studied, but our fundamental understanding of the molecular events in thyroid epithelial oncogenesis is still limited. Unreported data from our previous published global gene expression analysis revealed that the tumor suppressor gene aplysia ras homolog I (ARHI) is frequently underexpressed in FTCs. In this study, we elucidated the frequency and mechanism of ARHI silencing in benign and malignant thyroid neoplasia. We demonstrated that underexpression of ARHI occurs principally in FTCs (P = 0.0018), including its oncocytic variant (11 of 13), even at minimally invasive stage but not classic papillary thyroid carcinoma (two of seven) or follicular adenoma (FA) (three of 14). FTCs show strong allelic imbalance with reduction in copy number/loss of heterozygosity (LOH) in 69%, compared with less than 10% for FAs. In combination with our LOH data, bisulfite sequencing in a subset of samples revealed that FA displays a symmetric methylation pattern, likely representing one unmethylated allele and one presumptively imprinted allele, whereas FTC shows a virtually complete methylation pattern, representing LOH of the nonimprinted allele with only the hypermethylated allele remaining. Furthermore, we showed that pharmacologic inhibition of histone deacetylation but not demethylation could reactivate ARHI expression in the FTC133 FTC cell line. Therefore, our data suggest that silencing of the putative maternally imprinted tumor suppressor gene ARHI, primarily by large genomic deletion in conjunction with hypermethylation of the genomically imprinted allele, serves as a key early event in follicular thyroid carcinogenesis.     

Screening is associated with a lower risk of hepatocellular carcinoma-related mortality in patients with chronic hepatitis B

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Expression of stem-cell factor and its receptor c-kit protein in normal testicular tissue and malignant germ-cell tumours

The proto-oncogene c-kit and its ligand stemcell factor (SCF) may play an important role in the development of normal and malignant testicular tissue. This study investigates the presence of SCF and c-kit protein in 32 orchiectomy specimens of patients with testicular cancer, in 5 specimens of normal testicular tissue and in three established non-seminomatous germ-cell cancer cell lines (H12.1, H32, 577ML) by an immunohistochemical approach. Out of 9 testicular cancer specimens classified as pure seminomas, 7 (78%) showed a strong immunohistochemical reaction for both SCF and c-kit protein on the surface of the tumour cells. Fourteen non-seminomatous germ-cell tumours composed of embryonal carcinoma were completely negative for both SCF and c-kit protein and only faint positivity was found in 6 tumours (26%). Differentiated teratomatous structures within the specimens of nonseminomatous tumours showed a strong immunohistochemical reaction for SCF and c-kit protein in 8 of 11 (73%) cases. All three testicular cancer cell lines showed only faint staining reactions for c-kit protein and none for SCF. No secretion of SCF by the three lines in vitro was detected. The addition of high concentrations of SCF (100 ng/ml) to the testicular cancer cell lines in culture conditions without fetal calf serum resulted in a 1.4 to 3-fold growth stimulation compared to cell growth in serum-free medium alone. This effect was not detectable when the cells were cultured in serum-containing media. In the normal testicular tissue the germ-cells displayed a strong immunohistochemical reaction for c-kit protein while SCF positivity was found at the tubular membrane and on the surface of Sertoli cells. The SCF/c-kit system may possess a regulatory function in normal testicular tissue by possibly providing the microenvironment necessary for spermatogenesis. With the development of testicular cancer, this regulatory system seems to be lost, particularly in non-seminomatous germ-cell tumours. A growthstimulatory effect of high concentrations of SCF on nonseminomatous testicular cancer cell lines can be detected only in culture conditions with serum-free media. The effects achievable by the combination of SCF with other growth factors need to be further studied, as well as the role of the c-kit/SCF regulatory system for normal spermatogenesis and its possible implications for the understanding and treatment of male infertility.     

Effectiveness of progressive dose-escalation of exenatide (exendin-4) in reducing dose-limiting side effects in subjects with type 2 diabetes

BACKGROUND: Exenatide (exendin-4) exhibits dose-dependent glucoregulatory activity, but causes dose-limiting nausea and vomiting. This study was designed to formally assess the possibility of inducing tolerance to the side effects of nausea and vomiting at therapeutic doses of exenatide, using a dose-escalation methodology. METHODS: In this two-arm, triple-blind, multicenter study, 123 subjects with type 2 diabetes were enrolled and randomized; 99 (80.5%) of them completed the study. Subjects in the exenatide-primed arm received subcutaneous exenatide, starting at 0.02 micro g/kg three times a day (TID) and increasing in 0.02 micro g/kg per dose increments every 3 days for 35 days. Subjects in the exenatide-naive arm received placebo TID for 35 days. At the end of this 35-day regimen, subjects in both arms received the same highest dose of exenatide (0.24 micro g/kg TID) for 3 days. Thus, the exenatide-naive arm received exenatide for the first time on Day 35. RESULTS: The exenatide-primed arm had a lower proportion of subjects experiencing nausea and vomiting in response to exposure to the highest dose of exenatide (27 vs 56% in the exenatide-naive arm; p = 0.0018). Kaplan-Meier estimates of cumulative incidence were 0.28 in the exenatide-primed arm, compared with 0.68 in the exenatide-naive arm (p 相似文献