DFNB39, a recessive form of sensorineural hearing impairment, maps to chromosome 7q11.22-q21.12

This article describes the identification of a novel locus (DFNB39) responsible for an autosomal recessive form of hearing loss segregating in a Pakistani consanguineous family. The hearing impaired members of this family present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 7q with a maximum multipoint lod score of 3.8. The region of homozygosity spans a 19 cM region that is bounded by markers D7S3046 and D7S644.     

Renin angiotensin system modulates mTOR pathway through AT2R in HIVAN

Mammalian target of rapamycin (mTOR) has been reported to contribute to the development of HIV-associated nephropathy (HIVAN). We hypothesized that HIV may be activating renal tissue mTOR pathway through renin angiotensin system (RAS) via Angiotensin Receptor Type II receptor (AT2R). Renal tissues of Vpr transgenic and Tg26 (HIVAN) mice displayed enhanced phosphorylation of mTOR and p70S6K. Aliskiren, a renin inhibitor attenuated phosphorylation of both mTOR and p70S6K in renal tissues of HIVAN mice. Interestingly, Angiotensin Receptor Type I (AT1R) blockade did not modulate renal tissue phosphorylation of mTOR in HIVAN mice; on the other hand, AT2R blockade attenuated renal tissue phosphorylation of mTOR in HIVAN mice. In vitro studies, both renin and Ang II displayed enhanced mouse tubular cell (MTC) phosphorylation of p70S6K in a dose dependent manner. HIV/MTC also displayed enhanced phosphorylation of both mTOR and p70S6K; interestingly this effect of HIV was further enhanced by losartan (an AT1R blocker). On the other hand, AT2R blockade attenuated HIV-induced tubular cell phosphorylation of mTOR and p70S6K, whereas, AT2R agonist enhanced phosphorylation of mTOR and p70S6K. These findings indicate that HIV stimulates mTOR pathway in HIVAN through the activation of renin angiotensin system via AT2R.     

The Frequency and Functional Impact of Overlapping Hypertension on Hypertrophic Cardiomyopathy: A Single-Center Experience

J Clin Hypertens (Greenwich) Between 1995 and 2005, 196 adults with hypertrophic cardiomyopathy (HCM) were evaluated. Among these, 122 (62%, group 1) patients also had systemic hypertension. The clinical presentation, management, outcome, and echocardiographic findings of these patients were compared with 74 (38%, group 2) patients without systemic hypertension. Patients in group 1 were older at the time of HCM diagnosis and had a higher prevalence of diabetes (28% vs 9%; P=.02) and coronary artery disease (40% vs 25%; P=.03). In addition, echocardiography showed a significantly higher prevalence of systolic anterior motion of the anterior mitral valve in association with dynamic left ventricular outflow obstruction (52% vs 19%; P=.02) and mitral annular calcification (27% vs 13%; P=.03) in group 1 patients. Left ventricular wall thickness (17 mm vs 19 mm), end-diastolic diameter (42 mm vs 42 mm), resting outflow tract gradient >30 mm Hg (17% vs 16%), and ejection fraction (65% vs 64%) were similar in the two groups. HCM frequently coexists with systemic hypertension in the adult population. Presence of systemic hypertension in HCM patients is associated with older age and higher risk of diabetes, coronary artery disease, and noncardiac death.     

Increased levels of inflammatory mediators in children and adults infected with Vibrio cholerae O1 and O139

Investigations were carried out to study the production of factors associated with the innate immune response in the systemic and mucosal compartments in adults and children infected with Vibrio cholerae O1 and V. cholerae O139. The levels of nonspecific mediators of the innate defense system, i.e., prostaglandin E(2) (PGE(2)), leukotriene B(4) (LTB(4)), and lactoferrin (Lf), as well as myeloperoxidase (MPO), were elevated at the acute stage of the disease in stools obtained from both O1- and O139-infected adults and children. In the systemic compartment, the levels of Lf were increased after onset of disease, which in children remained elevated up to convalescence compared to the healthy controls. Increased concentrations of C-reactive protein were seen in the sera of adult cholera patients at the acute stage of infection. Elevated levels of the nitric oxide (NO*) metabolites (nitrite and nitrate [NO(2)(-) and NO(3)(-)]) were detected in plasma but not in urine. The activity of the scavenger of reactive oxygen species, superoxide dismutase, was higher in the plasma of adults immediately after the onset of disease, suggesting that an active scavenging of reactive oxygen species was taking place. The concentration of 8-iso-prostaglandin F(2 alpha) remained unchanged in the systemic and mucosal compartments in the study subjects. After the recovery of patients from cholera, the concentration of the majority of the metabolites decreased to baseline levels by day 30 after the onset of infection. Immunohistochemical staining showed increased tissue expression of MPO, Lf, and inducible nitric oxide synthase at the acute stage in the duodenal biopsies of adults and rectal biopsies obtained from children with cholera. Very little difference was seen in the levels of the different inflammatory mediators in patients infected with V. cholerae O1 or the encapsulated V. cholerae O139. In summary, these results suggest that elevated concentrations of Lf, MPO, PGE(2), LTB(4), and NO*, as well as other metabolites, during the acute stage of the disease indicate that the innate defense system, as well as the inflammatory process, is activated in both adults and pediatric patients infected with V. cholerae O1 and O139.     

Increased Levels of Inflammatory Mediators in Children and Adults Infected with Vibrio cholerae O1 and O139

Investigations were carried out to study the production of factors associated with the innate immune response in the systemic and mucosal compartments in adults and children infected with Vibrio cholerae O1 and V. cholerae O139. The levels of nonspecific mediators of the innate defense system, i.e., prostaglandin E₂ (PGE₂), leukotriene B₄ (LTB₄), and lactoferrin (Lf), as well as myeloperoxidase (MPO), were elevated at the acute stage of the disease in stools obtained from both O1- and O139-infected adults and children. In the systemic compartment, the levels of Lf were increased after onset of disease, which in children remained elevated up to convalescence compared to the healthy controls. Increased concentrations of C-reactive protein were seen in the sera of adult cholera patients at the acute stage of infection. Elevated levels of the nitric oxide (NO^·) metabolites (nitrite and nitrate [NO₂⁻ and NO₃⁻]) were detected in plasma but not in urine. The activity of the scavenger of reactive oxygen species, superoxide dismutase, was higher in the plasma of adults immediately after the onset of disease, suggesting that an active scavenging of reactive oxygen species was taking place. The concentration of 8-iso-prostaglandin F_2α remained unchanged in the systemic and mucosal compartments in the study subjects. After the recovery of patients from cholera, the concentration of the majority of the metabolites decreased to baseline levels by day 30 after the onset of infection. Immunohistochemical staining showed increased tissue expression of MPO, Lf, and inducible nitric oxide synthase at the acute stage in the duodenal biopsies of adults and rectal biopsies obtained from children with cholera. Very little difference was seen in the levels of the different inflammatory mediators in patients infected with V. cholerae O1 or the encapsulated V. cholerae O139. In summary, these results suggest that elevated concentrations of Lf, MPO, PGE₂, LTB₄, and NO^·, as well as other metabolites, during the acute stage of the disease indicate that the innate defense system, as well as the inflammatory process, is activated in both adults and pediatric patients infected with V. cholerae O1 and O139.     

Clinical “case series”: a concept analysis

Objectives

To analyze the concept of “case series” in the medical literature compared with case reports.

Methods

A PubMed search for articles published during 2009 which had “case series” in their title was performed. A total number of 621 articles were retrieved. 586 papers were included in the analysis and 35 were excluded (18 were commentary letters, 5 were not in English, and twelve could not be retrieved by our Library). The number of patients and category of these articles were analyzed.

Results

The median (range) of the number of cases of articles having “case series” in their title was 7 (1–6432) cases. 186/ 586 articles had less than 5 cases (31.7%, 95% CI (28.3–35.1%)). The median (range) of the number of cases of articles having “case report” as their publication type was 4 (1–178) cases. Out of the 219 articles categorized as case reports 114 (52.1%, 95% CI (45.6–58.6%)) had less than five cases.

Conclusions

The concept of “case series” is not well defined in the literature and does not reflect a specific research design. We suggest that a case series should have more than four patients while four paitents or less should be reported individually as case reports.     

Clinical presentation of postnatal and non-postnatal depressive episodes

BACKGROUND: The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. METHOD: In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. RESULTS: The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. CONCLUSIONS: The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.