Familial hypomagnesemia with hypercalciuria and nephrocalcinosis

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder that is frequently associated with progressive renal failure. The primary defect is related to impaired tubular reabsorption of magnesium (Mg) and calcium (Ca) in the thick ascending limb of Henle's loop. We have studied seven Arab patients with this syndrome who belong to four different families. The mean age at first presentation was 1.5+/-1.3 years (range 0.1-3 years) and at diagnosis 5.9+/-4.3 years (range 0.5-12 years). The presenting features were convulsions and carpopedal spasms (5 patients), polydipsia and polyuria (2 patients), rickets (2 patients), and recurrent urinary tract infections (1 patient). Bilateral nephrocalcinosis was observed in all patients. All patients had hypomagnesemia with a mean serum Mg of 0.45+/-0.09 mmol/l, an inappropriately high urine Mg of 2.07+/-0.73 mmol/24 h or fractional excretion of 15.3+/-7.1%, high urine Ca excretion of 4.1+/-1.2 mmol/24 h or urine Ca to creatinine ratio of 2.6+/-1.6, and normal serum potassium level of 4.4+/-0.34 mmol/l. All patients received Mg supplements and thiazide but exhibited slow worsening of their kidney function. After a mean follow-up of 4.4+/-3.9 years, one patient progressed to end-stage renal failure (ESRF). In conclusion, we report seven Arab patients with FHHNC syndrome. The clinical and biochemical data were similar to previous reports. However, they tend to show a slower rate of progression to ESRF.     

Lack of acculturation is a risk factor for diabetes in arab immigrants in the US

OBJECTIVE: To examine the relationship between dysglycemia (impaired fasting glucose, impaired glucose tolerance, and diabetes) and acculturation, physical activity, and perceived stress in Arab immigrants in the U.S. RESEARCH DESIGN AND METHODS: In a cross-sectional population-based study, we examined 520 Arab Americans, aged 20-75 years, who were born in the Middle East and immigrated to southeastern Michigan. Dysglycemia was assessed by history and with a 2-h 75-g oral glucose tolerance test. Acculturation, physical activity, and perceived stress were measured with standardized questionnaires. RESULTS: Associations were found between dysglycemia in men and older age at immigration, unemployment, speaking Arabic with friends, being less active in Arabic organizations, more frequent consumption of Arabic food, and less integration into American society. Dysglycemia in women was associated with being raised in rural areas of the Middle East, older age at immigration, longer length of stay in the U.S., not being employed outside the home, less than high school education, not attending Arabic or American schools, and not being able to read Arabic. Among men, older age at immigration, shorter length of stay in the U.S., less activity in Arab organizations, and eating Arabic food were associated with dysglycemia independent of age and BMI. Among women, acculturation was very low and was confounded with age and BMI as powerful risk factors for dysglycemia. No association was found between physical activity, perceived stress, and the risk of dysglycemia in either sex. CONCLUSIONS: Lack of acculturation is an important risk factor for dysglycemia in immigrant Arab Americans. Intervention programs aimed at diabetes prevention should consider the acculturation process.     

Structure modification in knee osteoarthritis: methodology and outcome parameters

Managing osteoarthritis (OA) with structure-modifying agents (SMAs) is an important emerging topic receiving increased attention from both lay individuals and health care professionals as a promising alternative in the management of OA. OBJECTIVE: To review the methodology and outcome parameters purported to be used in the assessment of the structure-modifying potential of various interventions. DESIGN: A Medline search was performed to select the relevant published articles. This review does not go into detail about various aspects of the design and conduct of structure-modifying studies; however, a vast number of relevant references are provided and may be accessed by interested readers. RESULTS: Enhancing the feasibility of SMAs trials aimed at documenting efficacy can be accomplished by carefully selecting: (1) the outcome parameters, (2) the imaging methodology, and (3) the patient population. Most of the relevant issues that need to be considered by investigators before embarking on a study of this nature have been addressed in this article. CONCLUSION: Most of the evidence to date focuses on the superiority of the radiographic-based techniques in measuring joint space narrowing among a homogeneous population of OA patients. More research is warranted before other techniques such as ultrasound, chondroscopy, and magnetic resonance imaging, can be proven to be reliable.     

Endotelin ETA and ETB receptor antagonism during cold preservation in renal transplantation

BACKGROUND: In this study, we investigated the effects of selective endothelin (ET) receptor antagonism during different periods of cold ischemia on glomerular and tubular function and long-term survival in renal transplantation. METHODS: Left renal transplantation was performed in Lewis rats after 2 hr of cold ischemia without (n=8) and with (n=6) ETA receptor antagonism and after 16 hr of cold ischemia without treatment (n=6), with ETA receptor antagonism (n=8) and with ETB receptor antagonism (n=6). A control group (n=8) underwent right nephrectomy and left renal denervation. The ETA and ETB receptor antagonists (BQ-610 and A-192621, respectively) were added to the preservation solution (EuroCollins). After transplantation, renal glomerular and tubular functions were monitored for up to 60 days or death. RESULTS: All animals in the control and 2-hr groups survived the follow-up protocol, with early postoperative recovery of glomerular and tubular function while the entire untreated 16-hr group died between day 3-6 postoperatively. BQ-610 treatment had no measurable effect on the renal function in the 2-hr group, however, it improved glomerular and tubular functions and led to 50% long-term survival (60 days) in the 16-hr group. A-192621 treatment had no effect on long-term survival or renal parameters. CONCLUSION: ETA receptor antagonism had protective renal effects after prolonged ischemic preservation in renal transplantation while ETB receptor antagonism had not.     

Need for instruction and support of the wives of patients with myocardial infarction

The study investigates the need for instruction and support among wives of patients with myocardial infarction, applying the 'stress' theory. The data were gathered by questionnaires completed by 59 wives of patients with myocardial infarction. Feelings and symptoms indicative of stress did occur among wives of the patients. They assessed instruction especially concerning home care, as being inadequate. They stated that the support they received had come largely from their own relatives; more than one third of the respondents said they had received support from a nurse; one fifth said they had not received it from anyone. The 'instruction' model for wives and other relatives of patients with myocardial infarction, introduced at the end of the article, emphasizes the importance of relevant information and support to the close relatives of patients with myocardial infarction.     

Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes

Proniosomal gels or solutions of flurbiprofen were developed based on span 20 (Sp 20), span 40 (Sp 40), span 60 (Sp 60), and span 80 (Sp 80) without and with cholesterol. Nonionic surfactant vesicles (niosomes) formed immediately upon hydrating proniosomal formulae. The entrapment efficiency (EE%) of flurbiprofen (a poorly soluble drug) was either determined by exhaustive dialysis of freshly prepared niosomes or centrifugation of freeze-thawed vesicles. The influence of different processing and formulation variables such as surfactant chain length, cholesterol content, drug concentration, total lipid concentration, negatively or positively charging lipids, and the pH of the dispersion medium on flurbiprofen EE% was demonstrated. Also, the release of the prepared niosomes in phosphate buffer (pH 7.4) was illustrated. Results indicated that the EE% followed the trend Sp 60 (C(18))>Sp 40 (C(16))>Sp 20 (C(12))>Sp 80 (C(18)). Cholesterol increased or decreased the EE% depending on either the type of the surfactant or its concentration within the formulae. The maximum loading efficiency was 94.61% when the hydrating medium was adjusted to pH 5.5. Increasing total lipid or drug concentration also increased the EE% of flurbiprofen into niosomes. However, incorporation of either dicetyl phosphate (DCP) which induces negative charge or stearyl amine (SA) which induces positive charge decreased the EE% of flurbiprofen into niosomal vesicles. Finally, in vitro release data for niosomes of Sp 40 and Sp 60 showed that the release profiles of flurbiprofen from niosomes of different cholesterol contents is an apparently biphasic release process. As a result, this study suggested the potential of proniosomes as stable precursors for the immediate preparation of niosomal carrier systems.     

Health Effects Reported by Adolescent Water Pipe and/or Cigarette Smokers Compared to Nonsmokers

Purpose

The purpose of this study was to determine the prevalence of respiratory and/or physical fitness health problems in adolescent (ages 18–21) water pipe (WP) smokers (with or without cigarette smoking), cigarette-only smokers, and nonsmokers.

Fetuin-A levels are increased in the adipose tissue of diabetic obese humans but not in circulation

Background

The hepatokine fetuin-A is linked to obesity and type 2 diabetes, but its presence and expression in adipose tissue remain unclear. In this study, we aimed to assess the circulating levels of fetuin-A and its expression in subcutaneous adipose tissue (SAT) from diabetic and non-diabetic obese subjects and their modulation by exercise.

Methods

SAT and blood were obtained from adults obese (diabetic, n=118 and non-diabetic, n=166) before and after a 3-month exercise program (diabetic, n=40 and non-diabetic, n=36, respectively). Plasma fetuin-A was assayed using ELISA. The presence and expression of fetuin-A in SAT, peripheral blood mononuclear cells (PBMCs) and cell lines (3T3-L1, THP-1, HepG2, RAW 264.7) were analysed using confocal microscopy, immunoblotting and qRT-PCR.

Results

Plasma fetuin-A level did not significantly differ between diabetic and non-diabetic obese subjects. However, when the non-diabetic group was divided into metabolically healthy and unhealthy phenotypes, significantly higher fetuin-A level was observed in the unhealthy sub-group. Circulating fetuin-A was mainly associated with glycaemic markers. In SAT, fetuin-A protein level was significantly higher in the diabetic obese subjects but its mRNA was not detected. Similarly, fetuin-A protein was detected in PBMCs, but its mRNA was not. In line with this, the use of various cell lines and culture media indicated that the presence of fetuin-A in SAT and PBMCs was due to its uptake from circulation rather than its endogenous expression. Finally, physical exercise decreased fetuin-A levels in both plasma and SAT in both groups.

Conclusions

Fetuin-A levels increased in association with diabetes in SAT but not in circulation in the obese subjects. Moreover, physical exercise decreased fetuin-A level. Fetuin-A potentially acts as a hepatokine taken up by other tissues, such as adipose tissue.

     

N-Acetyltransferase 2 and glutathione s-transferase M1 in colon and rectal cancer cases from an industrialized area

Apart from genetics, nutrition, and environment, occupational factors also play an important role in colon and rectal cancer development. The aim of this study was to examine these cancer types in an area of former coal, iron, and steel industries, which was found to display an increased incidence of colon cancer mortality. N-Acetyltransferase 2 (NAT2) and glutathione S-transferase M1 (GSTM1) genotypes were investigated in 108 colon cancer cases, 80 rectum cancer cases, and 188 controls (suffering from nonmalignant diseases). Further, in a pilot study, 28 colorectal cancer patients were NAT2 phenotyped by the caffeine test. Possible occupational and nonoccupational risk factors were investigated by a personal interview. The frequency of rapid NAT2 genotype was 35% in colon cancer cases, 47% in rectal cancer cases, and 42% in controls (GSTM1 0/0 genotype: 53, 46, and 47%, respectively). In the 29 patients with cancer in the ascending colon, 10% were of the rapid NAT2 genotype. In the pilot study the frequency of the rapid NAT2 phenotype was 49%. The only major professional group with an elevated risk was painters (colon cancer OR 2.48, 95% CI 0.4-15.23; rectal cancer OR 5.65, 95% CI 1.06-30.21). In contrast to early studies, in the present study the slow NAT2 status is overrepresented. As colorectal cancer is associated with nutrition and physical activity, present findings may be due to excessive physical heavy work and the resulting nutrition in this area.     

Trends in the Use of Antiepileptic Drugs among Pregnant Women in the US, 2001–2007: A Medication Exposure in Pregnancy Risk Evaluation Program Study

Background: Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001–2007. Methods: We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15–45 years on delivery date, who were members of MEPREP health plans (n = 585 615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD‐9 codes. Results: Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED‐exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. Conclusions: AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED‐exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.