Bladder and bowel control in children with cerebral palsy: case-control study

Aim

To determine the age of development of bladder and bowel control and the frequency of enuresis, encopresis, and urinary infections in children with cerebral palsy.

Methods

The study included 45 children with cerebral palsy who regularly attended a rehabilitation center in Isparta, Turkey, and two groups of age- and sex-matched children, 37 siblings of the children with cerebral palsy and 37 healthy children. Demographic data and information on the age of development of total bladder and bowel control and presence of possible urinary symptoms in children were collected from their caregivers by use of a questionnaire. Frequency of enuresis and encopresis was estimated among the children aged ≥5 years. A mid-way urinary sample was obtained from 40, 22, and 21 children in the cerebral palsy, siblings, and healthy children, respectively.

Results

The mean age of nighttime bladder and bowel control development was 47 months (95% confidence interval [CI], 35-58) and 45 (36-55) months, respectively, for the children with cerebral palsy, 35 months (95% CI, 24-46) and 26 months (95% CI, 24-28), respectively, for their siblings, and 27 months (95% CI, 22-33) and 25 months (95% CI, 23-27) months, respectively, for the healthy children. Among the children aged ≥5 years, enuresis was present in 11 of 34 children with cerebral palsy, 7 of 30 siblings, and 4 of 30 healthy children (P = 0.200), whereas encopresis was present in 5 children with cerebral palsy, one sibling, and one healthy child. Constipation was significantly more present in chidlren with cerebral palsy than in other two groups (P<0.001). Urine culture was positive in 13 children with cerebral palsy, 1 sibling, and 2 healthy chidlren (P = 0.024). There were no significant differences in other urinary symptoms and laboratory findings among the three groups.

Conclusion

The children with cerebral palsy gained bladder and bowel control at older age in comparison with their siblings and healthy children. They also had more frequent enuresis and urinary infections.Cerebral palsy represents a group of chronic, non-progressive motor disorders characterized by impaired voluntary movement resulting from prenatal developmental abnormalities or perinatal or postnatal central nervous system damage. Some people with cerebral palsy are also affected by other medical disorders, such as seizures, mental retardation, hearing and vision problems, and communication problems (1,2). The prevalence of cerebral palsy is approximately 2-3 per 1000 live births (1-3).The involuntary voiding of urine beyond the age of anticipated bladder control is defined as enuresis. The ability to void or inhibit voiding voluntarily at any degree of bladder filling commonly develops during the second and third year of life, and most children acquire an adult pattern of urinary control by the age of 4 (4,5). The fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defines enuresis and encopresis as involuntary or unintentional repeated voiding of urine or feces, respectively, into bed or clothes, which occurs twice a week for at least 3 consecutive months, and the child must be at least 4 years old (5). The bladder and bowel control typically develops in the following sequence: nocturnal bowel control, daytime bowel control, daytime control of voiding, and nocturnal control of voiding (5).Urinary incontinence or enuresis, fecal incontinence or encopresis, and constipation are common bowel and bladder problems among adults or children with cerebral palsy (6-11). Furthermore, age of achieving bladder and bowel control in the children with cerebral palsy are higher than in their healthy peers (9,12). The development of bladder and bowel control may be influenced by neurological impairment in the children with cerebral palsy. Additionally, the frequency of urinary tract infections in these children may be higher than in healthy ones (6,7). Thus it is important to think about the possibility of a bladder problem in any child with cerebral palsy who would be expected to be dry, particularly if there is a history of urinary tract infections (13).The healthy siblings of disabled children, including children with cerebral palsy, are exposed to emotional distress more often than other healthy children without disabled siblings (14), but they do not differ in health, nutritional, or growth status (15). Moreover, the siblings of children with cerebral palsy encourage their brother or sister to be more independent and thus may contribute to improvement of the functional status of children with cerebral palsy (16).Our aim was to determine the age of achieving bladder and bowel control and frequencies of enuresis, encopresis, and urinary infections in children with cerebral palsy in comparison with their healthy siblings and other healthy children.     

Evaluation of antinuclear antibodies by indirect immunofluorescence and line immunoassay methods′: four years′ data from Turkey

The presence of antinuclear antibodies (ANAs), directed against intracellular antigens, is a hallmark of systemic autoimmune rheumatic diseases. The indirect immunofluorescence (IIF) assay is among the most commonly used routine methods for ANA detection as the screening test. The objective of the study was to evaluate ANA patterns in a 4‐year period retrospectively. All 19 996 serum samples that were sent to the Laboratory of Medical Microbiology of the tertiary Hospital by any hospital department between 1 January 2009 and 1 January 2013 with a request to test for ANA, anti‐ENA or both were included in the study. Of these samples, 4375 (21.9%) were ANA‐IIF‐positive and 15621 (78.1%) were ANA‐IIF‐negative. The presented ANA‐positive samples consisted of 2392 (54.67%) homogenous, 818 (18.70%) speckled, 396 (9.05%) centromere, 242 (5.53%) nucleolar, 213 (4.87%) nuclear dots, 178 (4.07%) cytoplasmic (except for actin and golgi), 24 (0.55%) actin, 9 (0.21%) golgi, 53 (1.21%) nuclear membrane and 50 (1.14%) mixed pattern. Totally 7800 samples were examined by LIA. Of these samples, 3440 were positive and 4307 were negative with IIF and LIA. In addition, 22 samples were detected as IIF‐positive but LIA‐negative, whereas the rest 31 samples were IIF‐negative but LIA‐positive. ANA patterns in 22 IIF‐positive samples were homogenous (9), speckled (5), golgi (4), cytoplasmic (3) and nucleolar (1). SSA/Ro‐52, SSB/La and Scl‐70 positivity were detected in 31 IIF‐negative/LIA‐positive samples by LIA. The present study comes forward with its overall scope, which covers 4‐year data obtained in tertiary hospital located in the western part of Turkey.     

Evaluation of cases with a preliminary diagnosis of Crimean- Congo hemorrhagic fever and comparison of characteristics in patients admitted to a secondary care hospital in Kastamonu,Turkey

Background

Crimean-Congo hemorrhagic fever (CCHF) is an endemic disease in Turkey. The clinical presentation and laboratory findings are not specific especially in cases without hemorrhagic findings.

Objective

We aimed to evaluate CCHF cases and compare them with non-CCHF cases in terms of their characteristics during admission.

Methods

Cases with a preliminary diagnosis of CCHF at a secondary care hospital in Kastamonu in 2013 were evaluated, retrospectively. Cases testing RNA/IgM positive were considered as CCHF. Cases testing both RNA and IgM negative were considered as non-CCHF. The two groups were then compared in terms of their clinical, laboratory and epidemiological characteristics during admission.

Results

A total of 41 cases were tested and CCHF was found in 46.3% of cases. Fatality was 5.3% in CCHF cases. The frequency of tick bites and CK elevation in CCHF cases was significantly higher than non-CCHF cases (p<0.05). There were no significant differences between the two groups regarding other characteristics (p>0.05).

Conclusions

In cases with a preliminary diagnosis of CCHF, especially in cases without a history of tick bite and with normal CK levels during admission, performing tests for the differential diagnosis may be advisable without waiting for the results of tests for CCHF.     

L-carnitine reduces cochlear damage induced by gamma irradiation in Guinea pigs

L-carnitine (LC) protects cells from peroxidative damage. In this study, we tested whether L-carnitine (LC) prevents radiation-induced cochlear damage after total cranial irradiation (radiotherapy; RT). Male albino guinea pigs were randomly distributed in 3 groups. The Control group (n = 11) received neither LC nor irradiation, but saline solution ip and sham irradiation for 5 days. The RT group (n = 32) received saline solution ip as placebo therapy and exposure to total cranial irradiation of 33 Gy in 5 fractions of 6.6 Gy/day on 5 successive days, with a calculated (alpha/beta = 3.5) biological effective dose of fractionated irradiation equal to 60 Gy conventional fractionation. The LC + RT group (n = 36) received total cranial irradiation, plus LC (100 mg/kg/day, ip) for 5 days. The guinea pigs were killed at 4, 24, or 96 hr after the last dose of RT and the cochleas were enucleated for histopathologic examination. There was no cochlear degeneration in the control group. In the RT group, total cranial irradiation caused degeneration in stria vascularis (SV), spiral ganglion (SG), outer hair cells (OHC), and inner hair cells (IHC) of cochleas at 4, 24, and 96 hr. In the LC + RT group, LC administration reduced radiation-induced cochlear degeneration in SV and SG at 4, 24, and 96 hr, and in OHC and IHC at 24 and 96 hr (p <0.05). Thus, this study shows that L-carnitine can ameliorate radiation-induced cochlear damage in guinea pigs.     

Furosemide rescues hypercalciuria in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis model

Aim

Perturbed calcium homeostasis limits life expectancy in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC). This rare disease occurs by loss-of-function mutations in CLDN16 or CLDN19 genes, causing impaired paracellular reabsorption of divalent cations along the cortical thick ascending limb (cTAL). Only partial compensation takes place in the ensuing late distal convoluted tubule, connecting tubule, and collecting duct, where the luminal transient receptor potential channel V5 (TRPV5), as well as basolateral plasma membrane calcium ATPase (PMCA) and sodium-potassium exchanger (NCX1) mediate transcellular Ca²⁺ reabsorption. The loop diuretic furosemide induces compensatory activation in these distal segments. Normally, furosemide enhances urinary calcium excretion via inhibition of the aforementioned cTAL. As Ca²⁺ reabsorption in the cTAL is already severely impaired in FHHNC patients, furosemide may alleviate hypercalciuria in this disease by activation of the distal transcellular Ca²⁺ transport proteins.

Methods

Cldn16-deficient mice (Cldn16^−/−) served as a FHHNC model. Wild-type (WT) and Cldn16^−/− mice were treated with furosemide (7 days of 40 mg/kg bw) or vehicle. We assessed renal electrolyte handling (metabolic cages) and key divalent transport proteins.

Results

Cldn16^−/− mice show higher Ca²⁺ excretion than WT and compensatory stimulation of Cldn2, TRPV5, and NCX1 at baseline. Furosemide reduced hypercalciuria in Cldn16^−/− mice and enhanced TRPV5 and PMCA levels in Cldn16^−/− but not in WT mice.

Conclusions

Furosemide significantly reduces hypercalciuria, likely via upregulation of luminal and basolateral Ca²⁺ transport systems in the distal nephron and collecting duct in this model for FHHNC.     

The Bakri balloon for the management of postpartum hemorrhage in cases with placenta previa

Objective

To evaluate the success rate of the Bakri balloon in the event of uncontrollable hemorrhage due to placenta previa.

Study design

We evaluated 25 patients who were treated with the Bakri balloon who had severe postpartum hemorrhage with placenta previa and failed medical treatment with uterotonic agents.

Results

The Bakri balloon was inserted abdominally during cesarean section in 24 of 25 cases. In only one case was it inserted vaginally. The Bakri tamponade was effective in 22 cases (88%). There were three cases with failure: two patients needed an additional procedure (hypogastric artery ligation and B-Lynch suture) and one patient needed hysterectomy.

Conclusions

The Bakri balloon is the least invasive, rapid method in the management of bleeding due to placenta previa with minimal complications.     

Outcomes of random start versus clomiphene citrate and gonadotropin cycles in occult premature ovarian insufficiency patients,refusing oocyte donation: a retrospective cohort study

Abstract

The aim of this study is to present the clinical outcomes of a random start, a spontaneous folliculogenesis protocol versus Clomiphene Citrate and Gonadotropin treatment in women with occult premature ovarian insufficiency. Women underwent treatment between 1 February 2009, and 30 May 2016. 41 women were treated with the random start protocol while 48 cases received ovarian stimulation with clomiphene and gonadotropins. All included cases met the criteria of 4?months of oligo-ovulation, follicular-stimulating hormone levels over 30?IU/L and anti-Mullerian hormone levels below 0.30?ng/mL. The random start protocol involved following the subjects for up to 6?months until spontaneous folliculogenesis occurred. The mean number of oocytes collected, mature oocytes, fertilized oocytes, and grade II embryos were significantly higher in the random start protocol (p?<?.05). The doses of gonadotropin administration and hCG were significantly lower in the random start protocol (p?<?.05). The clinical pregnancy and live birth rates were significantly higher in the random start protocol (p?<?.05). Likely stimulation is of little benefit in women with occult premature ovarian insufficiency. Observation while waiting for spontaneous folliculogenesis results in better outcomes, and less oocyte collections.     

Antimicrobial effects of local anaesthetics

After the introduction of cocaine to the medical practice, local anaesthetics (LA) became essential in pain control. LA infiltration along the incision may be used to provide surgical anaesthesia or postoperative analgesia. This study aimed to compare the antimicrobial effects of the topical antimicrobial agent mupirocine with those of the LA lidocaine and the combination of lidocaine and adrenalin. In our study, the in vitro antimicrobial effects of 1 mL sterile saline, 20 mg/mL mupirocine, 20 mg/mL Lidocaine, and 20 mg/mL Lidocaine and Adrenaline were tested against Staphylococcus aureus American type culture collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922 as Group C (Control), Group M (Mupirocine), Group L (Lidocaine), and Group LA (Lidocaine + adrenaline), respectively. S aureus ATCC 29213, P aeruginosa ATCC 27853, and E coli ATCC 25922 were cultured onto Mueller–Hinton agar (Oxoid, UK) plates for 18 to 24 hours at 37°C. Colonies from these plates were suspended in sterile saline and a 0.5 McFarland turbidity standard suspension (corresponding to 1.5 × 10⁸ CFU/mL) of each isolate was prepared. S Aureus ATCC 29213 inhibition zone diameter values of Group M, Group LA, and Group L were significantly higher compared with the group C (P ˂ 0.05). P aeruginosa ATCC 27853 inhibition zone diameter values of Group M and Group LA were significantly higher compared with the group C (P ˂ 0.05). E coli ATCC 25922 inhibition zone diameter values of Group M, Group LA, and Group L were significantly higher compared to the group C (P ˂ 0.05). LA infiltration along the incision may be used to provide surgical anaesthesia or postoperative analgesia. Considering that LAs show antimicrobial effects besides their analgesic effects, they may contribute to preventing the development and reducing the rate of surgical infections, decreasing the requirement to administer antibiotics. However, caution should be exercised not to antagonise the effective treatment of surgical infections, remembering that controversy on the antimicrobial effects of LAs remains in the literature. Therefore, further comprehensive studies with larger patient populations are warranted to demonstrate the antimicrobial effects of LAs.     

Disruption of hepatocyte growth factor/c-Met signaling enhances pancreatic beta-cell death and accelerates the onset of diabetes

OBJECTIVE

To determine the role of hepatocyte growth factor (HGF)/c-Met on β-cell survival in diabetogenic conditions in vivo and in response to cytokines in vitro.

RESEARCH DESIGN AND METHODS

We generated pancreas-specific c-Met-null (PancMet KO) mice and characterized their response to diabetes induced by multiple low-dose streptozotocin (MLDS) administration. We also analyzed the effect of HGF/c-Met signaling in vitro on cytokine-induced β-cell death in mouse and human islets, specifically examining the role of nuclear factor (NF)-κB.

RESULTS

Islets exposed in vitro to cytokines or from MLDS-treated mice displayed significantly increased HGF and c-Met levels, suggesting a potential role for HGF/c-Met in β-cell survival against diabetogenic agents. Adult PancMet KO mice displayed normal glucose and β-cell homeostasis, indicating that pancreatic c-Met loss is not detrimental for β-cell growth and function under basal conditions. However, PancMet KO mice were more susceptible to MLDS-induced diabetes. They displayed higher blood glucose levels, marked hypoinsulinemia, and reduced β-cell mass compared with wild-type littermates. PancMet KO mice showed enhanced intraislet infiltration, islet nitric oxide (NO) and chemokine production, and β-cell apoptosis. c-Met-null β-cells were more sensitive to cytokine-induced cell death in vitro, an effect mediated by NF-κB activation and NO production. Conversely, HGF treatment decreased p65/NF-κB activation and fully protected mouse and, more important, human β-cells against cytokines.

CONCLUSIONS

These results show that HGF/c-Met is critical for β-cell survival by attenuating NF-κB signaling and suggest that activation of the HGF/c-Met signaling pathway represents a novel strategy for enhancing β-cell protection.Type I diabetes is an autoimmune disease that results from cellular cytotoxicity leading to selective and progressive destruction of insulin-secreting cells (1–3). Many growth factors known to control cell growth and survival in physiologic and pathologic conditions are expressed in the pancreas and could potentially participate in an autocrine/paracrine fashion in the final fate of β-cells in an autoimmune environment. Overexpression of IGF-1, transforming growth factor-β, or granulocyte macrophage-colony stimulating factor ameliorates islet infiltration and β-cell death in mouse models of increased islet inflammation and diabetes (4–6). However, the role of endogenous pancreatic growth factors in type I diabetes has not been examined. Because growth factors can locally affect β-cell survival, neogenesis, and regeneration, and modulate chemokine production and immune responses, alterations in the level/activation of growth factor signaling pathways might contribute to the delay/acceleration of the onset of diabetes.Hepatocyte growth factor (HGF)/c-Met signaling pathway participates in the control of multiple biological functions, including development, proliferation, survival, regeneration, and branching morphogenesis (7). HGF binds with high affinity to, and induces the dimerization of, c-Met, its transmembrane tyrosine kinase receptor (8). Deletion of exon 16 of the c-Met gene, which encodes Lys¹¹⁰⁸ (ATP binding site), essential for the kinase activity of this receptor, in knockout mice results in embryonic lethality (9). These mice display a phenotype identical to HGF knockout mice (10). Both HGF and c-Met are expressed in the pancreas; HGF localizes to endothelial, islet, and mesenchymal cells, and c-Met is expressed in islet, ductal, and pancreatic progenitor cells (11–14). Conditional ablation of the c-Met gene in mouse β-cells using RIP-Cre and lox-c-Met mice leads to deficient insulin secretion without alteration of β-cell mass (12,13). On the other hand, HGF overexpression in the β-cell of transgenic mice increases β-cell replication, mass, and function (15,16). Furthermore, HGF improves islet graft survival in animal models of diabetes (17–19). HGF positively influences autoimmune responses, reducing the severity of autoimmune myocarditis and arthritis (20,21). HGF also downregulates airway and kidney inflammation, and inflammatory bowel disease (22–24). Whether HGF plays a role in autoimmune diabetes is unknown.To address the function of c-Met in the development, growth, and maintenance of β-cells under physiologic conditions, as well as its role in β-cell survival and response to injury in vivo, we generated pancreas-specific c-Met-null (PancMet KO) mice. We report that although c-Met is dispensable for normal β-cell growth and function under basal conditions, it is critically important for β-cell survival in diabetogenic conditions. β-Cell survival is dramatically worsened in the absence of HGF/c-Met signaling, resulting in accelerated diabetes onset. These observations also apply to human β-cells, underscoring a therapeutic opportunity for the HGF/c-Met signaling pathway in human diabetes.