Biomedical subjects

E John

Publications and source records attributed to E John.

At least 19 recordsLinked to original sources

PubMed2004

Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations.

Women with mutations of the genes BRCA1 or BRCA2 are at increased risk of ovarian cancer. Oral contraceptives protect against ovarian cancer in general, but it is not known whether they protect against the disease in carriers of these mutations. We obtained self-reported lifetime histories of oral contraceptive use from 451 women who carried mutations of BRCA1 or BRCA2. We used conditional logistic regression to estimate the odds ratios associated with oral contraceptive use, comparing the histories of 147 women with ovarian cancer (cases) to those of 304 women without ovarian cancer (controls) who were matched to cases on year of birth, country of residence and gene (BRCA1 vs BRCA2). Reference ages for controls had to exceed the ages at diagnosis of their matched cases. After adjusting for parity, the odds-ratio for ovarian cancer associated with use of oral contraceptives for at least 1 year was 0.85 (95 percent confidence interval, 0.53-1.36). The risk decreased by 5% (1-9%) with each year of use (P for trend=0.01). Use for 6 or more years was associated with an odds-ratio of 0.62 (0.35-1.09). These data support the hypothesis that long-term oral contraceptive use reduces the risk of ovarian cancer among women who carry mutations of BRCA1 or BRCA2.

Adult↗

PubMed2003

Living-related bowel transplantation to treat short bowel syndrome in a four-year-old child: a case report.

PURPOSE: Short bowel syndrome (SBS) is an extremely challenging clinical problem in children. Although many patients can be maintained for a period of time on total parenteral nutrition (TPN), many of these children suffer from the morbidity and mortality associated with sequential central line infections, venous thromboses, and TPN-induced liver failure. Intestinal transplantation often is the only chance for long-term survival. Unfortunately, many children die every year waiting for size-matched cadaveric intestine to become available. METHODS: After our success with living-related bowel transplantation in adults, the authors successfully transplanted 150 cm of maternal ileum into a 4-year-old 10-kg child with profound malnutrition from SBS and advanced TPN-induced liver failure. Because of the size mismatch, the abdominal cavity could not be closed primarily. The defect was covered with absorbable mesh and subsequently with skin graft. RESULTS: The patient is home with excellent bowel and liver function, off hyperalimentation, and on a regular diet. No rejection has been encountered. CONCLUSIONS: Living-related intestinal transplantation is a life-saving alternative to cadaveric intestinal transplantation in children with short bowel syndrome.

Child, Preschool↗

PubMed2001

Umbilical cord blood lactate in normal infants: comparison between two methods of measurement.

OBJECTIVES: Firstly, to determine the accuracy of the Radiometer ABL 625 lactate electrode (Radiometer Medical Pty Ltd, Nunawading, Victoria, Australia) by comparing the lactate values obtained by this method to those obtained with the Hitachi 917 lactate analyser (Boehringer Mannheim Corporation, Charlottetown, Prince Edward Island, Canada). Secondly, to determine the effect of delay in measurement on blood lactate levels. METHODOLOGY: Umbilical venous (UCV) blood samples were obtained from healthy term infants delivered vaginally. Lactate levels were measured with the Radiometer ABL 625 lactate electrode in the Neonatal Intensive Care Unit, Westmead Hospital and with the Hitachi 917 lactate analyser in 49 paired samples. In addition 26 UCV blood samples were placed in ice slurry and a further 26 samples at room temperature and blood lactate was measured at 5-min intervals for 30 min to determine the change of lactate levels with time. RESULTS: The lactate levels obtained from the Radiometer ABL 625 lactate electrode were consistently lower than the levels obtained from the Hitachi 917 lactate analyser (mean difference - 0.24), but the correlation was high (r = 0.97). The blood lactate levels increased at the rate of 0.012 mmol/L per min if the blood was left at room temperature. The lactate levels remained stable for 20 min if the blood was placed in ice slurry. CONCLUSION: The Radiometer ABL 625 lactate electrode was easy to use and there was high correlation with the values obtained by the standard laboratory method. The blood specimen must be place in an ice slurry if a delay in analysis is anticipated.

Analysis of Variance↗

PubMed2001

Inspired gas temperature during mechanical ventilation: effects of environmental temperature and airway temperature probe position.

OBJECTIVES: To determine the inspired gas temperature during mechanical ventilation with: (i) five different humidicrib temperatures; (ii) two airway temperature probe (ATP) positions; and (iii) four ATP adaptors. METHODOLOGY: An observational study in the Neonatal Intensive Care Laboratory, Westmead Hospital. The inspired gas temperature was measured at the proximal end of the endotracheal tube (ETT) during conventional mechanical ventilation using a Tele-thermometer. Inspired gas temperature measurements were made with: (i) the humidicrib temperature set at 30.8. 32.9, 35.2, 36.2. or 37.2 degrees C; (ii) the ATP either (A) positioned inside the humidicrib at the distal end of the inspiratory tubing or (B) positioned outside the humidicrib 50 cm proximal to the ETT, with the inspired gas temperatures set at 36.5 and 39.0 degrees C, respectively; and (iii) the measurements repeated with four different ATP adaptors at each humidicrib temperature and each ATP position. RESULTS: With the ATP inside the humidicrib, there were no significant differences between set and actual inspired gas temperature. However, with the ATP outside the humidicrib, there were significant decreases in inspired gas temperature at each humidicrib temperature. For instance, with the ATP outside the humidicrib and set at 39.0 degrees C, the inspired gas temperature decreased to 34.7+/-0.2 degrees C at a humidicrib temperature of 30.8 degrees C and to 37.7+/-0.2 degrees C at a humidicrib temperature of 37.2 degrees C. The type of ATP adaptor also had a significant effect on inspired gas temperature. CONCLUSIONS: With the ATP placed outside the humidicrib and with variations of humidicrib temperature, infants are likely to have inspired gas temperatures that are significantly different to the desired temperature. Certain ATP adaptors cause these variations in inspired gas temperature to be more pronounced. Extreme care must be used to avoid suboptimal inspired gas temperatures with these environmental variations and the ATP positioned outside the humidicrib.

Environment, Controlled↗

PubMed2001

Inspired gas humidity during mechanical ventilation: effects of humidification chamber, airway temperature probe position and environmental conditions.

OBJECTIVES: To determine the inspired gas humidity during mechanical ventilation with: (i) four different humidification chambers; (ii) two airway temperature probe (ATP) positions; (iii) five different humidicrib temperatures; and (iv) insulating the inspiratory limb with bubble wrap. METHODOLOGY: An observational study in the Neonatal Laboratory and Neonatal Intensive Care Unit, Westmead Hospital. The humidity of the inspired gas was measured at the proximal end of the endotracheal tube (ETT) during mechanical ventilation. Inspired humidity measurements were made with four different humidification chambers (Fisher & Paykel (F&P Healthcare Pty Ltd, Auckland, New Zealand) auto refill MR290. F&P manual refill MR310, Suruga (Suruga Inc. Humidifiers, Vincent Medical, Dongguan, China) manual refill MI-20 and MI-10F) with the humidity control (relative humidity setting) set at - 2. Measurements were made with the ATP positioned either; (A) at the distal end of the inspiratory tube inside the humidicrib or (B) outside the humidicrib 50 cm proximal to the ETT. The inspired gas temperatures were set at 36.5 degrees C and at 39.0 degrees C, respectively. For each of the different humidification chambers and ATP positions, inspired humidity measurements were made with the humidicrib temperature set at 30.8, 32.9, 35.2, 36.2, or 37.2 degrees C. Two further sets of measurements were made, one with the inspiratory limb insulated with bubble wrap and the second set without bubble wrap. RESULTS: There were significant differences in inspired humidity with the four humidification chambers at both ATP positions at all humidicrib temperatures. Both Suruga humidification chambers produced significantly higher inspired gas humidities under most conditions. Positioning the ATP outside the humidicrib produced significantly higher inspired gas humidities than with the ATP inside the humidicrib. Insulating the inspiratory tubing with bubble wrap also significantly improved the inspired gas humidity. CONCLUSIONS: Significant differences in inspired gas humidity were found with the humidification chambers tested. The position of the ATP and the set temperature had a significant impact on the absolute humidity of the inspired gas. In general, higher inspired gas humidities were obtained with the ATP outside the humidicrib. However, condensation of water close to the ETT appeared at low humidicrib temperatures (< 36.2 degrees C) with the ATP outside the humidicrib and extreme care should be taken that particulate water does not enter the lungs under these conditions.

Environment, Controlled↗

PubMed2001

Effects of tezosentan, a dual endothelin receptor antagonist, on the cardiovascular and renal systems of neonatal piglets.

BACKGROUND/PURPOSE: Endothelin is a potent biological vasoactive mediator in the cardiovascular and renal systems. Little is known of the effects of endothelin antagonism on the developing heart and kidney, and we hope to show that endothelin does have an important role in the cardiovascular and renal systems of the developing neonate. In this study the authors have examined the effects of tezosentan, a nonselective endothelin-A and endothelin-B receptor antagonist designed for parenteral use, on the cardiovascular and renal systems of healthy neonatal piglets. METHODS: Eight, 7- to 10-day old domestic piglets weighing 2.5 to 3.0 kg were anesthetized, intubated, and ventilated with catheters placed into the jugular vein, left ventricle, and femoral artery. Urine output was monitored via a suprapubic cystostomy. After baseline data were obtained the piglets received tezosentan (1 mg/kg/h) for 1 hour. A set of data was collected just before discontinuation of the 1-hour infusion of tezosentan and another set was collected 1 hour after the discontinuation of the drug. Mean arterial pressure (MAP), heart rate (HR), and urine output (UV) were monitored continuously and cardiac index (CI), systemic vascular resistance (SVR), renal blood flow (RBF), and renal vascular resistance (RVR) were calculated from gamma counts obtained from injections of radio-labeled microspheres at end of the different time periods. Glomerular filtration rate (GFR) was obtained by the sodium iothalamate method. Data were averaged and plotted versus time and analyzed statistically by a Student's t test. RESULTS: (P <.05 versus baseline*). In our experimental animals the infusion of tezosentan diminished MAP and SVR from baseline values of 94 +/- 7 mm Hg and 0.14 +/- 0.03 mm Hg/mL/min, respectively to TEZO values of 62 +/- 4* mm Hg and 0.07 +/- 0.02* mm Hg/mL/min. CI increased from 278 +/- 58 to 367 +/- 75* mL/min/kg with tezosentan. There also was a statistically significant increase in RBF from 1.16 +/- 0.38 to 1.86 +/- 0.37* mL/min/kg, an increase in UV from 0.57 +/- 0.24 to 0.64 +/- 0.12* mL/min, a decrease in RVR from 4.60 +/- 1.47 to 2.03 +/- 0.36* mm Hg/mL/min, and no change in the GFR. CONCLUSIONS: The inhibition of endothelin receptors with tezosentan produced a statistically significant effect on the piglet cardiovascular system with a drop in MAP and SVR and an increase in CI and HR. It also produced a statistically significant increase in RBF and UV and a decrease in RVR without affecting GFR. J Pediatr Surg 36:1824-1828.

Animals↗

PubMed2000

Enhanced internal dynamics of a membrane transport protein during substrate translocation.

Conformational changes are essential for the activity of many proteins. If, or how fast, internal fluctuations are related to slow conformational changes that mediate protein function is not understood. In this study, we measure internal fluctuations of the transport protein lactose permease in the presence and absence of substrate by tryptophan fluorescence spectroscopy. We demonstrate that nanosecond fluctuations of alpha-helices are enhanced when the enzyme transports substrate. This correlates with previously published kinetic data from transport measurements showing that millisecond conformational transitions of the substrate-loaded carrier are faster than those in the absence of substrate. These findings corroborate the hypothesis of the hierarchical model of protein dynamics that predicts that slow conformational transitions are based on fast, thermally activated internal motions.

Animals↗

PubMed2000

Enhancement of noradrenergic neural transmission: an effective therapy of myasthenia gravis: a report on 52 consecutive patients.

Neurochemical, neuroautonomic and neuropharmacological assessments carried out on all our myasthenia gravis (MG) patients showed that they presented a neural sympathetic deficit plus excessive adrenal-sympathetic activity. These abnormalities were registered during the basal (supine-resting) state, as well as after several stress tests (orthostasis, exercise, oral glucose and buspirone). In addition, MG patients showed increased levels of free-serotonin (f5HT) in the plasma, supposedly associated with the increased platelet aggregability which we found in all MG patients. As the above trio of neurochemical disorders (low noradrenergic-activity + high adrenergic-activity + increased f-5HT plasma levels) is known to favor Th-1 immunosuppression + Th-2 predominance, we outlined a neuropharmacological strategy for reverting the above neurochemical disorder. This treatment provoked sudden (acute), and late sustained improvements. Acute effects have been attributed to the increase of alpha-1 activity at the spinal motoneuron level. Late improvements always paralleled a significant normalization of immunological disorders. Complete normalization was registered only in non-thymectomized MG patients.

Adolescent↗

PubMed1999

Effect of unilateral testicular torsion on blood flow and histology of contralateral testes.

BACKGROUND/PURPOSE: Infertility occurs in 25% of patients after unilateral testicular torsion; hence, the authors examined hemodynamic and histological changes in both testes after acute testicular torsion in neonatal piglets. METHODS: The animals were anesthetized, intubated, ventilated, catheterized, and assigned randomly to a sham group or one of three experimental groups undergoing 720 degrees torsion of the left testis for 8 hours after which it was untwisted in group I and removed in group II. In group III, both testes were removed. Data were collected at baseline (T = 0), 4 hours (T = 4), and 8 hours of torsion (T = 8) and at the ninth hour of the experiment (T = 9). Testicular blood flow was determined by using radiolabeled microspheres. The testes also were examined blindly with routine and electron microscopy. RESULTS: In group I, testicular blood flow decreased in the affected testis during torsion and increased significantly after detorsion, whereas blood flow to the contralateral testis increased significantly after detorsion. Sham-operated animals showed no histological abnormality in either testis. In all torsion groups, the affected testis showed extensive changes caused by hemorrhagic necrosis. The contralateral testis only showed changes in group I. CONCLUSION: Unilateral testicular torsion resulted in ipsilateral damage caused by a decrease and subsequent increase in blood flow while in the contralateral testis; damage was the result of a significant increase in blood flow after detorsion.

Animals↗

PubMed1999

New animal model to evaluate testicular blood flow during testicular torsion.

BACKGROUND/PURPOSE: Unilateral testicular torsion is known to cause infertility because of damage to the contralateral testis. Testicular damage has been attributed to many different mechanisms, one of which is altered contralateral blood flow. In our experiment, in an effort to identify the reason for contralateral testicular injury, the authors developed an accurate method of measuring blood flow in both testes before, during, and after unilateral torsion. METHODS: Four- to 6-week-old piglets weighing 4 to 6 kg were studied. The animals were anesthetized, intubated, ventilated, and catheterized for vascular access. Piglets were assigned randomly to a sham group or a group undergoing 360 degrees or 720 degrees torsion of the left testis (n = 5 per group) for 8 hours, after which it was untwisted. Data were collected at baseline (T = 0), 8 hours of torsion (T = 8), and 1 hour after detorsion (T = 9). Mean arterial blood pressure and heart rate were monitored continuously. Testicular blood flow was determined using radiolabeled microspheres. Blood flow data were evaluated by analysis of variance. RESULTS: In the 360 degrees torsion group, blood flow changes were insignificant during torsion and after detorsion. In the 720 degrees torsion group, blood flow to the twisted testis was reduced significantly, whereas the contralateral testis was unaffected. One hour after detorsion, blood flow to both testes was increased significantly. CONCLUSIONS: The authors describe a new animal model to evaluate testicular blood flow during and after testicular torsion. Increased blood flow after detorsion may be the cause of testicular damage in patients with unilateral testicular torsion.

Animals↗

PubMed1999

Serial phospholipid analysis in preterm infants: comparison of Exosurf and Survanta.

The initial clinical response to synthetic or natural surfactant is different and long-term complications from meta-analysis suggest that bronchopulmonary dysplasia and retinopathy of prematurity may be increased in infants given synthetic surfactant. It is possible that this is due to differences in the phospholipid composition of lung fluid following administration of these surfactants. Infants less than 32 weeks gestation with respiratory distress syndrome (RDS) were randomly assigned to receive either Exosurf, an artificial surfactant, or Survanta, a natural surfactant. Endotracheal or hypopharyngeal aspirates were obtained from these infants and from control infants who had normal lungs. The aspirates were taken prior to and up to 28 days following surfactant administration. The different phospholipids were separated by thin layer chromatography and expressed as a percent of total phospholipid measured. Infants with normal lungs had a higher proportion of phosphatidylcholine than those with RDS prior to treatment. The infants with normal lungs had a greater proportion of phosphatidylinositol in their lung aspirates than both treatment groups at 24 h. Infants in the Survanta group had a higher proportion of phosphatidylglycerol at 48 h than the group with normal lungs. No other differences were found in phospholipid composition up to 28 days. There were no major differences in the phospholipid profile in infants with RDS treated with either Exosurf or Survanta. In conclusion, neither the clinical differences initially seen between infants treated with either Exosurf or Survanta, nor the long-term outcome could be explained by the phospholipid composition of serial samples of lung aspirates.

Analysis of Variance↗

PubMed1999

Role of ureaplasma urealyticum in lung disease of prematurity.

AIM: To examine the role of Ureaplasma urealyticum colonisation or infection in neonatal lung disease. METHODS: Endotracheal aspirates from ventilated infants less than 28 weeks of gestation were cultured for U urealyticum and outcomes compared in infants with positive and negative cultures. RESULTS: U urealyticum was isolated from aspirates of 39 of 143 (27%) infants. Respiratory distress syndrome (RDS) occurred significantly less often in colonised, than in non-colonised infants (p=0.002). Multivariate logistic regression analysis showed that in singleton infants, ureaplasma colonisation was the only independent (negative) predictor of RDS (OR 0.36; p=0. 02). Both gestational age (OR 0.46; p=0.006) and isolation of U urealyticum (OR 3.0; p=0.05) were independent predictors of chronic lung disease (CLD), as defined by requirement for supplemental oxygen at 36 weeks of gestational age. Multiple gestation was also a major independent predictor of RDS and CLD. CONCLUSIONS: Colonisation or infection with ureaplasma apparently protects premature infants against the development of RDS (suggesting intrauterine infection). However, in singleton infants, it predisposes to development of CLD, independently of gestational age. Treatment of affected infants after birth is unlikely to significantly improve the outcome and methods are required to identify and treat the women with intrauterine ureaplasmal infection, before preterm delivery occurs.

Humans↗

PubMed1999

Correlation of flow probe determinations of common carotid artery blood flow and internal carotid artery blood flow with microsphere determinations of cerebral blood flow in piglets.

We investigated whether blood flow determined by a flow probe situated on one common carotid artery provided an accurate estimation of unilateral cerebral blood flow (CBF) in piglets. In eight anesthetized, mechanically ventilated piglets, blood flow determined by an ultrasonic flow probe placed on the right common carotid artery was correlated with CBF determined by microspheres under two experimental conditions: 1) before ligation of the right external carotid artery with both the right external and internal carotid circulations intact [common carotid artery blood flow (CCABF) condition], and 2) after ligation of the right external carotid artery (ipsilateral to the flow probe) with all residual right-sided carotid artery blood flow directed through the right internal carotid artery [internal carotid artery blood flow (ICABF) condition]. The left carotid artery was not manipulated in any way in either protocol. Independent correlations of unilateral CCABF and ICABF with microsphere-determined unilateral CBF were highly significant over a 5-fold range of CBF induced by hypercarbia or hypoxia (r = 0.94 and 0.92, respectively; both p < 0.001). The slope of the correlation of unilateral CCABF versus unilateral CBF was 1.68 +/- 0.19 (SEM), suggesting that CCABF overestimated CBF by 68%. The slope of the correlation of unilateral ICABF versus unilateral CBF did not differ significantly from unity (1.06 +/- 0.15), and the y intercept did not differ significantly from zero [-1.3 +/- 5.2 (SEM) mL]. Consequently, unilateral ICABF determined by flow probe accurately reflected unilateral CBF determined by microspheres under these conditions. Flow probe assessments of CCABF and ICABF in piglets may provide information about dynamic aspects of vascular control in the cerebral circulation that has heretofore been unavailable.

Animals↗

PubMed1999

Retinopathy of prematurity in infants < 32 weeks' gestation at birth in New South Wales in 1993 and 1994.

OBJECTIVE: To study the incidence and severity of retinopathy of prematurity (ROP) in infants < 32 weeks' gestation. DESIGN: Review of the records maintained in the New South Wales Neonatal Intensive Care Unit Study (NICUS) database on infants admitted to the neonatal intensive care units (NICU) in NSW from 1 January 1993 to 31 December 1994. RESULTS: In the more premature infants, 23-26 weeks' gestation, 65% developed ROP (102 of 157 examined for ROP). Forty-four infants (28%) developed severe ROP (Stage >/= 3 ROP), 19 infants (12.1%) required cryo/laser therapy and one infant (0.6%) in this group had a retinal detachment. One hundred and fifty-seven of 159 surviving infants (98.7%) were examined for ROP. In the infants 27-28 weeks' gestation, 38.3% developed ROP (103 of 269 examined for ROP). Fifteen infants (5.6%) developed severe ROP, seven infants (2. 6%) required cryo/laser therapy for threshold ROP and three infants (1.1%) in this group had a retinal detachment. Two hundred and sixty-nine of 299 surviving infants (90%) were examined for ROP. In the infants 29-31 weeks' gestation, 10.8% developed ROP (48 of 443 examined for ROP). Six infants (1.4%) developed severe ROP, one infant (0.2%) required cryo/laser therapy for threshold ROP and no infant in this group had a retinal detachment. However, only 443 of 681 surviving infants (65.1%) in this group were examined for ROP. Of the four infants with detached retinas, one was a 25 week gestation infant weighing 840 g, two were 27 weeks' gestation weighing 960 and 980 g and one infant was a 28 week gestation infant weighing 620 g. No infant developed Stage 5 ROP. CONCLUSION: In the more mature infants 29-31 weeks' gestation, the rate of ROP is low, although severe ROP still occurs. However, only 65.1% of these infants were examined for ROP and we should be diligent in screening for ROP in the sicker infants in this group. The incidence of severe ROP as well as the rate of cryo/laser therapy in premature infants 23-26 weeks' in NSW has not changed since the increases seen in the early 1990s. Retinal detachment also occurs in the infants 27-28 weeks' gestation and it is important that all these infants are screened for ROP.

Gestational Age↗

PubMed1998

Cytological changes in endotracheal aspirates associated with chronic lung disease.

Endotracheal aspirates taken serially from mechanically ventilated premature infants born at < 28 weeks gestation between March 1992 and August 1993 were studied to determine whether early cytological changes would be a good predictor of lung damage in infants who develop chronic lung disease (CLD). CLD was diagnosed if the infant required supplemental oxygen at 36 weeks corrected gestational age. Fifty-five infants were enrolled in the study, five died and of the 50 infants remaining, 17 (34%) developed CLD. The infants with CLD had a significantly lower gestation (25.5 +/- 1.8 (mean +/- 1 SD) versus 26.2 +/- 0.9 weeks, p < 0.05), significantly more required surfactant (14/17 vs. 16/33, p < 0.05) and were ventilated for a significantly longer period (43.3 +/- 26.6 vs. 19.3 +/- 12.8 days, p < 0.0001). Endotracheal aspirate cytology showed that infants with CLD had significantly more degenerated columnar epithelial cells on day 3 (p = 0.001), and more neutrophils on day 10 (p = 0.007). Though not predictive of CLD, cytological changes consistent with bronchial epithelial and pulmonary damage followed by an inflammatory response were found in the tracheal aspirates of a group of infants clinically diagnosed with CLD.

Chronic Disease↗

PubMed1998

Retinopathy of prematurity in infants <29 weeks' gestation at birth in New South Wales from 1986-92.

OBJECTIVE: To study the effect of increased survival of infants <29 weeks' gestation on the incidence and severity of retinopathy of prematurity (ROP). METHODOLOGY: Review of prospective records from 1986 to 1992 kept in the New South Wales (NSW) NICUS database on infants admitted to the neonatal intensive care units (NICU) in NSW. The survival rate and the incidence and severity of ROP on all infants <29 weeks' gestation admitted to the NICUs in NSW from 1 July 1986 to 31 December 1987 were compared to a similar group of infants admitted from 1 January 1992 to 31 December 1992. RESULTS: There was a significant difference in the survival rate of infants admitted between the two periods (235 of 376, 62.5% survival vs 255 of 336, 75.9% survival, respectively, P<0.0001). The odds ratio for survival adjusted for gestational age in the second period was 1.76 [1.24, 2.48 (95% confidence interval), P<0.002]. There was a slight increase in ROP in the second period (79 of 172 examined, 45.9% ROP vs 133 of 238 examined, 55.8% ROP, respectively). There was a rise in the number of infants with Stage 3 ROP in the second time period (14 of 172 examined, 8.1% ROP vs 41 of 238 examined, 17.2% ROP, respectively). However, fewer infants had detached retinas or > or = Stage 4 ROP in the second group [7 of 172, (4.1 %) vs 3 of 238, (1.3%), respectively]. This may be a reflection of the increase in the use of cryo- or laser therapy for Stage 3 ROP with 'plus' disease [2 of 172 examined, (1.2%) vs 18 of 238 examined, (7.6%), respectively]. CONCLUSIONS: With the increase in survival of the very preterm infant in recent years, there has been an increase in severe ROP (> or = Stage 3) in NSW. Despite the increased survival of the highest at-risk group (24- to 26-week gestation infants), there have been fewer cases of retinal detachment. There was also a rise in the number of infants receiving cryo- or laser therapy intervention.

Gestational Age↗

PubMed1997

Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III.

Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination of this gene reveals loss-of-function mutations that impair renal chloride reabsorption in the thick ascending limb of Henle's loop. Mutations in seventeen kindreds have been identified, and they include large deletions and nonsense and missense mutations. Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA. Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper- or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent. These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents.

Bartter Syndrome↗

PubMed1997

Chronic oxygen dependency in infants born at 24-32 weeks' gestation: the role of antenatal and neonatal factors.

OBJECTIVES: To study the incidence of chronic oxygen dependency (COD) among ventilated survivors born at 24-32 weeks gestation from 1986 to 1994 and to identify antenatal and neonatal factors that may have changed with time; and to identify antenatal and neonatal factors that could contribute to the development of COD in infants born at 24-32 weeks gestation using a case control model. METHODOLOGY: Infants born at 24-32 weeks gestation in one tertiary referral centre between 1986 and 1994 and admitted to the neonatal intensive care unit for respiratory support were studied. Data accumulated prospectively since 1986 in survivors of ventilation were analyzed to identify antenatal and neonatal factors that could have changed with time. The cohort of infants who developed COD were matched for gestation and time of birth with a control group of infants who did not have COD. Significant factors that could have contributed to the development of COD were identified using forward logistic regression analysis. RESULTS: The number of mothers admitted for threatened premature labour (TPL), and pregnancy induced hypertension decreased with time while the use of antenatal steroids and maternal antibiotics increased. More infants were delivered by Caesarean section during the later years. There was an increase in neonatal septicaemia with time while there were decreases in hyaline membrane disease, pneumothorax, pulmonary interstitial emphysema, use of high peak inspiratory pressure (PIP) and high inspired oxygen. The incidence of COD decreased. The case controlled study revealed a significant positive association between COD and male gender, birthweight less than the 10th percentile for gestation, PIP over 30 cm H2O, septicaemia and significant patent ductus arteriosus (PDA) requiring indomethacin. There was a negative association with TPL. CONCLUSIONS: Further decrease in COD can be achieved only if septicaemia, PDA and the use of high PIP can be avoided. The most effective way of reducing the incidence of COD is by reducing the incidence of prematurity.

Apgar Score↗