X‐linked mental retardation with alacrima and achalasia—Triple A syndrome or a new syndrome?

We describe a consanguineous Israeli Arab kindred with five males in two interrelated families with intellectual disabilities, alacrima, achalasia, and mild autonomic dysfunction. Adrenal function is normal. Their phenotype is similar to the phenotype observed in autosomal recessive Triple A syndrome except for the presence of mental retardation in all affected individuals. The pedigree is compatible with either X‐linked or autosomal recessive inheritance. Sequencing of the AAAS gene causing autosomal recessive Triple A syndrome did not reveal mutations. Genotyping of affected family members identified a 16.4 Mb continuous segment of identical alleles shared by the patients between markers rs2748314 and rs5906782 on Xp11.23‐p21, establishing linkage to chromosome X. This study further confirms genetic heterogeneity in Triple A syndrome and points to a clinically different subtype including significant cognitive impairment. © 2011 Wiley‐Liss, Inc.     

Pregnancy outcome after ICSI with thawed testicular sperm from men with non-obstructive azoospermia compared to ICSI with ejaculated sperm from men with severe oligoasthenoteratozoospermia and IVF with normal ejaculated sperm

The aim of the study was to evaluate the clinical pregnancy outcomes, fetal complications and malformation rate of intracytoplasmic injection of thawed cryopreseverd sperm extracted by testicular aspiration from men with non-obstructive azoospermia (NOA) compared with intracytoplasmic injection of fresh ejaculated sperm from men with severe oligoteratoasthenozoospermia (OTA) and standard in vitro fertilization using ejaculated sperm from normospermic men. The mean oocyte fertilization rate was significantly lowest for ICSI with testicular aspirated sperm (NOA group). However, there was no significant difference among the three groups in pregnancy outcomes, namely rates of spontaneous abortion, biochemical pregnancy, extrauterine pregnancy, singleton multifetal pregnancy, preterm delivery before 36 weeks’ gestation, maternal complications, transfer to the neonatal intensive care unit, intrauterine growth restriction or fetal malformations. These results suggest that despite some earlier findings that intracytoplasmic injection of aspirated sperm from men with NOA is associated with lower fertilization rates and embryo quality, the pregnancy and immediate neonatal outcomes may be unaffected.     

DNA bending by an adenine–thymine tract and its role in gene regulation

To gain insight into the structural basis of DNA bending by adenine-thymine tracts (A-tracts) and their role in DNA recognition by gene-regulatory proteins, we have determined the crystal structure of the high-affinity DNA target of the cancer-associated human papillomavirus E2 protein. The three independent B-DNA molecules of the crystal structure determined at 2.2-A resolution are examples of A-tract-containing helices where the global direction and magnitude of curvature are in accord with solution data, thereby providing insights, at the base pair level, into the mechanism of DNA bending by such sequence motifs. A comparative analysis of E2-DNA conformations with respect to other structural and biochemical studies demonstrates that (i) the A-tract structure of the core region, which is not contacted by the protein, is critical for the formation of the high-affinity sequence-specific protein-DNA complex, and (ii) differential binding affinity is regulated by the intrinsic structure and deformability encoded in the base sequence of the DNA target.     

Intravenous Iron in Heart Failure: Beyond Targeting Anemia

Iron deficiency is commonly seen in congestive heart failure (CHF) in both anemic and nonanemic patients. In six studies in which these iron-deficient patients with CHF were treated with intravenous (IV) iron, five found an improvement in the hemoglobin. In uncontrolled and controlled studies, the New York Heart Association (NYHA) class, quality of life, and exercise capacity were improved consistently with IV iron. In some studies, cardiac function also was improved. In one large, double-blind, placebo-controlled study of IV iron, the patient global assessment, quality of life, and NYHA class improved rapidly in both those who were anemic or not anemic. In contrast to these studies, another controlled study of anemia in CHF showed no effect of oral iron on hemoglobin or on any cardiac parameters over 1 year. These studies suggest that CHF in both anemic and nonanemic iron-deficient patients may benefit from a course of IV iron, but not oral iron.     

The Association in Elderly Hospitalized Patients,Between Psychotropic Drugs and Hip Fractures Resulting from Falls

Background/Study Context: Psychotropic drug treatment has been associated with increased risk for falls and hip fractures in elderly patients. The authors examined the association between drug treatment and hip fractures resulting from falls in elderly hospitalized patients, focusing on the medications’ anticholinergic properties.

Methods: This retrospective case-control study was conducted in an acute geriatric ward in a general medical center. Medical records, including demographic, clinical, biochemical, and pharmacological variables, of elderly patients with hip fractures from falls (N = 185), admitted during a 2-year period, were reviewed and compared with a control group (N = 187) of patients matched for age and gender and without hip fractures.

Results: The usage rates of antipsychotics, antidepressants, mood stabilizers, and various nonpsychiatric medications were similar in the two groups, except for hypnotics-anxiolytics (higher rates in hip-fracture patients). The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and diastolic blood pressure constituted very modest predictors of falls (R² = .038, p = .004). There were no significant differences in the anticholinergic burden values, clinical dementia ratings, and comorbidity burden between the two groups.

Conclusion: The rate of psychotropic drug use in general and their anticholinergic burden are similar in acutely admitted elderly patients with or without hip fractures. However, higher usage rate of anxiolytics found in the patients with hip fractures may indicate that this is a risk factor for hip fractures related to falls in elderly patients living in the community.     

Prevalence of anemia in patients admitted to hospital with a primary diagnosis of congestive heart failure

OBJECTIVES: To find the prevalence of anemia in patients hospitalized with the primary diagnosis of congestive heart failure (CHF). BACKGROUND: There is growing evidence that anemia is common in CHF and may contribute to the high morbidity and mortality associated with this condition. However, there is considerable disagreement about the prevalence of anemia in this condition. METHODS: In 338 consecutive patients who were admitted to the medical wards with a primary diagnosis of CHF we extracted from the charts the hemoglobin (Hb), serum creatinine, age, sex, New York Heart Association (NYHA) functional class, presence of smoking, diabetes, hypertension, hyperlipidemia and the primary cardiac etiology of the CHF. Anemia was considered to be present when the Hb on admission was <12 g/dl. RESULTS: All the patients were NYHA functional class III-IV. One hundred seventy seven (52.4%) of the 338 patients had a Hb on admission that was <12 g/dl. The mean Hb for the entire group was 12.0+/-1.8 g/dl. One hundred three (51.0%) of the 202 males were anemic compared to 74 (54.4%) of the 136 women. The mean serum creatinine was 1.7+/-1.1 mg/dl. The prevalence of renal insufficiency (serum creatinine >1.5 mg%) was 47.6%. There was a negative correlation between the level of serum creatinine and Hb (r=-0.294) P<0.00001. Of the 177 patients who were anemic, most of 114 (64.4%) had a serum creatinine >1.5 mg/dl. CONCLUSIONS: Anemia is a common finding in patients hospitalized with CHF and most anemic CHF patients have some degree of renal insufficiency. In view of the negative effect of anemia on cardiac function, it may be a common and important contributor to the mortality and morbidity of CHF in these patients.     

Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal

Features that distinguish tumor vasculatures from normal blood vessels are sought to enable the destruction of preformed tumor vessels. We show that blood vessels in both a xenografted tumor and primary human tumors contain a sizable fraction of immature blood vessels that have not yet recruited periendothelial cells. These immature vessels are selectively obliterated as a consequence of vascular endothelial growth factor (VEGF) withdrawal. In a xenografted glioma, the selective vulnerability of immature vessels to VEGF loss was demonstrated by downregulating VEGF transgene expression using a tetracycline-regulated expression system. In human prostate cancer, the constitutive production of VEGF by the glandular epithelium was suppressed as a consequence of androgen-ablation therapy. VEGF loss led, in turn, to selective apoptosis of endothelial cells in vessels devoid of periendothelial cells. These results suggest that the unique dependence on VEGF of blood vessels lacking periendothelial cells can be exploited to reduce an existing tumor vasculature.     

Freeze-etch study of collagen

The freeze-fracture technique was used to study the fine structure of native collagen from rat tendon and lung. The collagen filaments were organized into a spiraled lamellar substructure within each fibril. Small particles, representing the broken ends of the collagen filaments, were found in nearly straight rows when the lamellae were broken tranversely. Filamentous connections were shown which span the interfibrillar matrix and unite all of the fibrils into a reticular network. The fibrils were coated with material that was greatly hydrated in vivo. Sublimation occurred more rapidly from some portions of the coating substance than from others, resulting in a banding pattern with a 610 Å repeat distance.