Association between malnutrition-inflammation score and risk of subsequent self-reported bone fractures in prevalent kidney transplant recipients.

Chronic inflammation and protein energy wasting (PEW) syndrome are common in kidney transplant recipients (KTR). The presence of inflammation and PEW syndrome can directly affect bone resorption and bone formation, leading to bone loss and fractures. We showed PEW is independently associated with new clinically detected bone fractures in prevalent KTR. INTRODUCTION: Kidney transplant recipients (KTR) have a 4-fold higher risk of fracture compared to the general population. Chronic inflammation and PEW syndrome are common in KTR and are associated with poor outcomes. We hypothesized that the Malnutrition-Inflammation Score (MIS), a validated measure of PEW, is associated with higher risk of bone fractures in KTR. METHODS: This prospective cohort study included 839 prevalent KTR from a Central European academic center. MIS, a semiquantitative instrument of PEW, was calculated at the study entry. Self-reported history of fractures was recorded during the 2-year follow-up period. The association between MIS and bone fractures was examined in logistic regression analyses with adjustment for age, gender, eGFR, smoking habits, history of pre-transplant bone fractures, and acute rejection. RESULTS: Mean age was 51 ± 13 years, and 56% of patients were males with median (interquartile range) transplant vintage 69 (38-112) months, estimated glomerular filtration rate 55 ± 21 ml/min/1.73 m2, and calculated MIS 3 (2-4) at enrollment. Fifty-five (7%) patients experienced self-reported bone fractures during the 2-year follow-up period. Higher MIS score showed linear association with increased risk of fracture. Each one-point higher MIS was associated with 23% higher risk of bone fractures (odds ratio (OR) and 95% CI 1.23, 1.12-1.34), which remained significant after multivariable adjustments (OR 1.17, 95% CI 1.06-1.29). CONCLUSION: The MIS is independently associated with new clinically detected bone fractures in prevalent KTR.

Prediction of tubulo-interstitial injury by Doppler ultrasound in glomerular diseases: value of resistive and atrophic indices.

BACKGROUND: Doppler ultrasound is increasingly used in Nephrology for diagnosis of renovascular hypertension and evaluation of allograft dysfunction. However, its utility in glomerular disease remains controversial. OBJECTIVES: Using Doppler Ultrasound, we prospectively tested the role of resistive and atrophic indices in predicting tubulointerstitial lesions in patients with glomerular disease as demonstrated by renal biopsy. METHODS: Seventy one patients with primary or secondary glomerular diseases were examined by Doppler ultrasonography immediately before renalbiopsy. The resistive and atrophic indices (RI & AI) were calculated and compared with histologic changes in biopsy specimen. RESULTS: Receiver Operator Characteristics analysis showed RI of 0.60 as an optimal value for discriminating tubulointerstitial changes with sensitivity of 82.7% and specificity of 92%. An AI of 0.65 was shown to be optimal for discriminating tubulointerstitial injury with sensitivity of 69.2% and specificity of 85%. The combination of the two indices had not been found to be superior to either index alone. There was a significant correlation between atrophic and resistive indices. (r=0.358, p< 0.01). It was observed that older age, smoking, elevated AI and RI, low GFR, high serum cholesterol and Hypertension were found to be significantly associated with the presence of tubulointerstitial injury in the univariate analysis whereas only elevated AI and RI were found to predict tubulointerstitial injury in multivariate analysis. CONCLUSION: Measurement of RI by Doppler ultrasound can be considered as a supplementary diagnostic tool in glomerular diseases to predict the severity of tubulointerstitial injury.

Nephrocalcinosis in siblings--familial hypomagnesemia, hypercalciuria with nephrocalcinosis (FHHNC syndrome).

Familial Hypomagnesemia, Hypercalciuria with Nephrocalcinosis is a rare autosomal recessive inherited disease associated with renal failure. Two girls born of consanguineous parentage aged 16 and 17 presented to us with renal failure, nephrocalcinosis and bone deformities. On evaluation they were found to have hypomagnesemia, hypercalciuria, increased fractional excretion of magnesium, hypocitraturia, renal failure and elevated PTH. Their parental screening was normal. There were no extra-renal features in them. One sibling had nephrolithiasis and the stone analysis revealed calcium phosphate stones. Both were treated with sodium bicarbonate, thiazides, calcitriol and calcium carbonate. They did not require dialysis during hospital stay. Both of them were treated conservatively. They are on regular outpatient follow up. The primary defect in this syndrome is impaired paracellular reabsorption of magnesium and calcium in the medullary thick ascending limb. Mutations in the PCLN-1gene which encodes for the tight junction protein paracellin -1 is identified as the underlying genetic defect. Ocular abnormalities and deafness are the commonly reported associations. End stage renal failure usually occurs in second to third decade. Renal transplantation is the definite treatment.

Lymphoblastic lymphoma presenting as bilateral renal enlargement diagnosed by percutaneous kidney biopsy: Report of three cases.

Renal involvement by lymphoma can be a diagnostic challenge. Acute kidney injury (AKI) is an unusual manifestation of lymphomatous infiltration in the kidneys. We report three cases of lymphoblastic lymphoma, a very rare form of lymphoma, presenting with AKI and bilateral enlargement of kidneys, diagnosed by percutaneous kidney biopsy. Lymphomatous infiltration should be suspected with such clinical presentation. Kidney biopsy is a valuable diagnostic tool, to establish the correct diagnosis and subtype of lymphoma for timely initiation of therapy for these aggressive hematological malignancies.

Continuous negative extrathoracic pressure and positive end-expiratory pressure. A comparative study in Escherichia coli endotoxin-treated neonatal piglets.

Recent clinical studies have suggested that improvement in pulmonary gas exchange with the use of continuous negative extrathoracic pressure (CNEP) in conjunction with intermittent mandatory ventilation (IMV) may be due to increased pulmonary blood flow. Accordingly, we investigated the effects of CNEP vs positive end-expiratory pressure (PEEP) in ventilated neonatal piglets after Escherichia coli endotoxin was administered to induce pulmonary hypertension. Two experimental groups of piglets with six in each, were subjected to three 30-min alternating periods--6 cm H2O CNEP with 6 cm H2O PEEP, beginning 2 h after endotoxin infusion. End-expiratory lung volume (EELV) increased similarly from baseline (13 +/- 2 mL/kg) with both CNEP (28 +/- 2 mL/kg) and PEEP (29 +/- 2 mL/kg). In addition, the increase in PaO2 from baseline with CNEP (106 +/- 9 to 135 +/- 7 mm Hg) was similar to that with PEEP (114 +/- 11 to 132 +/- 6 mm Hg). Further, no differences were found in dynamic lung compliance, EELV, lung resistance, blood gas indexes, or hemodynamics, including transmural pulmonary artery pressure and pulmonary vascular resistance between CNEP and PEEP. With transpulmonary pressure and transrespiratory pressure equal, CNEP in tandem with IMV is physiologically equivalent to PEEP and IMV.

Preservation of pulmonary function in the ventilated neonatal piglet with normal lungs.

Little attention has been focused on the progressive pulmonary deterioration which occurs in mechanically ventilated infants with normal or mildly abnormal lungs. We hypothesized that lung function would deteriorate over a 24-hr period in anesthetized neonatal piglets with normal lungs mechanically ventilated at 2 cm H2O PEEP (2PEEP group). We further hypothesized that an intermittent lung inflation procedure consisting of 15 out of 60 min of increasing lung distention (4, 8, 12 cm H2O PEEP), with the remaining 45 min at 2 cm H2O PEEP (Inflation group) would prevent this deterioration in lung function, similar to piglets mechanically ventilated continuously at 6 cm H2O PEEP (6PEEP). Results indicate that 2PEEP piglets experienced progressive deterioration in lung function, including dynamic lung compliance (-42%) and lung resistance (+55%). In contrast, inflation piglets and 6PEEP piglets had no deterioration in lung function. Hemodynamics were similar between groups, although they were the most stable in the 6PEEP group. Histopathological changes were not significantly different. We conclude that (1) prolonged mechanical ventilation at 2 cm H2O PEEP in neonatal piglets resulted in progressive deterioration in pulmonary function, (2) intermittent lung inflation or continuous 6 cm H2O PEEP prevented deterioration, and (3) functional changes occurred without changes in histopathology. Lung inflation strategies other than PEEP can be used to prevent deterioration in lung function which accompanies prolonged mechanical ventilation in anesthetized nonspontaneously breathing piglets with normal lungs.

Continuous negative extrathoracic pressure versus positive end-expiratory pressure in piglets after saline lung lavage.

Recent reports have suggested that substituting continuous negative extrathoracic pressure (CNEP) for positive end-expiratory pressure (PEEP) may result in clinical benefits to infants with pulmonary disease. Other studies have suggested potential hemodynamic advantages. We compared the effects of CNEP and PEEP in 13 mechanically ventilated newborn piglets after acute lung injury induced by saline lavage. The piglets were instrumented, saline-lavaged, and exposed to 15 minute periods of incremental CNEP (-3, -6, -9, -12 cmH2O) (n = 7) or PEEP (3, 6, 9, 12 cmH2O) (n = 6). We measured and/or calculated dynamic lung compliance (CLdyn), lung resistance (RL), end-expiratory lung volume (EELV), blood gases, cardiac output (CO), heart rate (HR), transmural vascular pressures, and pulmonary and systemic vascular resistance. Pulmonary function abnormalities after saline lavage included decreased PaO2, CLdyn, EELV, and increased PaCO2 and RL (P < 0.05). Except for decreased CO, lung inflation with both CNEP and PEEP resulted in large increases in PaO2 without major pulmonary or hemodynamic effects. Other than differences in EELV at 3, 6, and 9 cmH2O distending pressure, there were no differences in pulmonary function or hemodynamics between sequences of incremental CNEP and PEEP. We conclude that CNEP and PEEP are physiologically equivalent in this model of acute lung injury.

Exogenous surfactant decreases oxygenation in Escherichia coli endotoxin-treated neonatal piglets.

Abnormalities of pulmonary surfactant function have been described in association with the acute respiratory distress syndrome (ARDS). Because gram-negative sepsis is a common cause of ARDS, we treated neonatal piglets with Escherichia coli endotoxin to create a neonatal ARDS model. We hypothesized that under these conditions administration of exogenous surfactant would improve pulmonary function. Study groups included: control (n-8), Exosurf (5 mL/kg, 13.5 mg phospholipid/mL, n-7), Survanta (4 mL/kg, 25 mg phospholipid/mL, n-6), and saline (5 mL/kg, n = 6). E. coli endotoxin 12 micrograms/kg was infused over 30 min and resulted in significant pulmonary and hemodynamic abnormalities, histopathologic evidence of nonhomogeneous lung injury, and elevated protein levels in bronchoalveolar lavage washings. Neither Exosurf nor Survanta ameliorated the pulmonary effects of endotoxin. Instead, there was a prolonged decrease in arterial oxygen tension (PaO2) and dynamic lung compliance after administration of surfactant and saline. Distribution of a bolus of Exosurf was uneven throughout the lung. We conclude that in this neonatal piglet model of ARDS, bolus surfactant administration had a detrimental effect on oxygenation and pulmonary function.

Exosurf treatment investigational new drug phase: effect of an individualized third dose in infants with respiratory distress syndrome.

Of 95 infants treated with the synthetic surfactant, Exosurf, under a Treatment Investigational New Drug protocol, 17 received one dose, 40 received two, and 38 received three doses. Seventy-six (80%) of the infants were treated by rescue protocol. We retrospectively reviewed the clinical course of the 67 surviving rescue infants. We found that, compared to one- and two-dose infants, those treated with three doses of Exosurf were more premature, smaller, required a longer ventilator course, and had more frequent complications, including patent ductus arteriosus (PDA), intraventricular hemorrhage, nosocomial pneumonia, and apnea. They required higher oxygen concentrations starting 8 hr after their first dose and higher mean airway pressure (MAP) from the time of their second dose. These trends continued during all subsequent time points, as compared to infants treated with two doses. The third dose was administered an average of 17 hr after the second, resulting in little change of MAP, but some reduction in oxygen requirements. By 24 hr after the last dose, only 4% of three-dose infants were extubated compared with 30% of the two-dose and 71% of one-dose infants. In conclusion, repeated administration of Exosurf is not equally effective in every treated infant with respiratory distress syndrome (RDS) and complications of prematurity may affect or accompany poor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Ontogeny of epithelial modulation of airway smooth muscle function in the guinea pig.

The purpose of this study was to investigate the ontogeny of guinea pig airway smooth muscle (ASM) responses and the epithelial modulation of these responses. Paired tracheal rings from fetal, newborn, and adult guinea pigs were studied. One of each pair was denuded of airway epithelium (AE) by gentle rubbing. Isometric tension was measured in rings mounted in organ baths filled with Krebs' solution. Cumulative dose-response curves were generated by adding either acetylcholine (ACh) or histamine over a concentration range of 10(-8)-10(-4) M. Significant agent-specific, age-related differences in maximal contraction were seen for both ACh and histamine in intact tissues (Ach: for fetus 66.7 +/- 6.2 x 10(-2) g/mg wet wt, for newborn 51.4 +/- 6.2, for adult 29.3 +/- 2.6; histamine: for fetus 46.1 +/- 5.1, for newborn 72.9 +/- 6.0, for adult 25.3 +/- 3.2). Similar differences in sensitivity to both agents were observed (EC50 with ACh: for fetus 0.80 +/- 0.11 x 10(-6) M; for newborn 0.85 +/- 0.26 x 10(-6) M; for adult 1.7 +/- 0.20 x 10(-6) M; EC50 with histamine; for fetus 1.88 +/- 0.50 x 10(-6) M; for newborn 1.34 +/- 0.16 x 10(-6) M; for adult 3.78 +/- 0.75 x 10(-6) M). Removal of AE caused a significant decrease in maximal responses to ACh in fetal tissue, a smaller, insignificant one for newborn and a nonsignificant alteration for adult tissues. Age-related sensitivity difference was abolished with removal of AE to ACh but not to histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of reversing distending pressure sequences in the neonatal piglet.

We studied different sequences of lung inflation in ventilated newborn piglets with normal lungs in order to determine the effects of sequence, magnitude and duration of distending pressure on pulmonary function, and/or hemodynamics. End-expiratory pressure was varied using a continuous negative extrathoracic pressure (CNEP) device. Three groups of ventilated piglets with normal lungs were exposed to 2 cmH2O increments of CNEP from -2 to -12 cmH2O, and to decrements from -12 to -2 cmH2O, or to only -6 cmH2O. Lung inflation sequence, magnitude of inflation pressure, and duration of inflation had significant effects on end-expiratory lung volume and lung compliance at numerically equivalent pressure levels. End-expiratory lung volume and lung compliance varied (at four and five of six inflation pressures studied) by as much as 68% and 104%, respectively. Hemodynamic effects of the lung inflation sequence were more variable; those found to be different at numerically equivalent pressure levels were associated with changes in lung compliance and ventilation. Differences in pulmonary mechanics can best be explained by the effects of lung inflation on alveolar recruitment versus overinflation.

Personal computer teleradiology interhospital image transmission of neonatal radiographs to facilitate tertiary neonatology telephone consultation and patient transfer.

OBJECTIVE: Our purpose was to study the ability of personal computer teleradiology (PCT) to improve the quality of communication between physicians during newborn infant transfers and consultations. STUDY DESIGN: In the first part of the study 36 radiographs of neonatal intensive care unit patients were transmitted by PCT. The pediatrician reviewed the original films and three neonatologists reviewed the PCT images. Their interpretations were scored by use of criteria established by a neutral reader. In the second part chest x-ray films (CXR) of 31 newborns weighing > 2000 gm with respiratory distress were transmitted by PCT. A pediatrician and three neonatologists participated in an exercise to simulate a telephone neonatology consultation. Patient severity assessments as measured by assignments to receive intermediate or intensive care were compared before and after neonatologists viewed the PCT image of the CXR. RESULTS: In part 1 of the study neonatologists correctly identified 98%, 91%, and 98% of the x-ray interpretation scoring items, whereas at best the pediatrician identified 82% of the scoring items (p = 0.002). In part 2 neonatologists correctly assigned patient care levels an average of 73% after reviewing a standard clinical profile and a written description of the infant's CXR. After reviewing a PCT image of the infant's CXR, patient care level assignments were correctly assigned an average of 67%. The interpretation of the PCT CXR image was consistent with the radiologic report of record in 90 of 93 interpretations (31 cases read by three neonatologists). CONCLUSIONS: PCT represents an inexpensive means to accurately send a radiographic image over the phone as part of a telephone consultation. Neonatologists were able to interpret teleradiology images more accurately than a pediatrician reviewing the original film. Although this did not result in an improvement in the neonatologists' ability to determine patient severity on the basis of the model used in part 2, their identification of serious radiographic findings missed by the pediatrician can only suggest that teleradiology may be beneficial in certain instances. Although verbal communication can often suffice in a telephone consultation or transfer, there may be specific instances when visualizing a radiographic image such as an x-ray film or computed tomographic scan can provide important information that cannot be optimally described verbally. Rural hospitals can form interhospital image transmission links with tertiary center resources.

Congenital chylothorax and mediastinal neuroblastoma.

This is the first reported association of congenital chylothorax and mediastinal neuroblastoma in a newborn infant. The infant exhibited features of both congenital and acquired chylothorax. Resolution of the chylothorax occurred following ligation of thoracic duct after failure of conservative management with multiple thoracentesis and chest tube drainage.

Early experience with inhaled nitric oxide for the treatment of infants and children with pulmonary hypertension.

When nitric oxide (NO), an endogenous regulator of smooth muscle tone, is administered by inhalation, it acts as a selective pulmonary vasodilator. This report details the treatment with inhaled NO of the first 11 patients in Hawaii.

Monozygotic twins discordant for trisomy 13.

Monozygotic twins with discordant karyotypes are rare. We report a case of monozygotic twins discordant for trisomy 13 by amniocyte karyotypes. Ultrasound revealed multiple congenital anomalies in Twin A (47,XY,+13), none in Twin B (46,XY), and monochorionic-diamniotic placentation. Zygosity testing performed both prenatally and after birth supported monozygosity. Twin A died in the neontal period. Twin B survived and had normal physical examination, but peripheral blood karyotype revealed 20% mosaicism for trisomy 13. Monochorionic-diamniontic placentation with vascular anastomoses was confirmed by pathological examination. In this paper, we discuss the various mechanisms by which monozygotic twins may have discordant karyotypes. The surviving twin, structurally and developmentally normal at 6 months of age, will be monitored for potential complications of uniparental disomy of chromosome 13 and trisomy 13 mosaicism.

Epidemiologic trend changes in acute renal failure--a tertiary center experience from South India.

BACKGROUND: There are little data on the incidence of acute renal failure (ARF) from India due to the absence of central registry. The etiology, course, and outcome of ARF differ in various parts of India. Significant trend changes were reported even within a same center over a period of time. AIM: To find out the epidemiologic trend changes in ARF patients, the authors compared the profile of patients admitted by the Department of Nephrology from 1995-2004 with previously published data from 1987-1991. METHODS: Data collected from case records of patients admitted with ARF were systemically analyzed for age, gender, etiology, course, and outcome. A total of 32 variables were collected per person retrospectively. The chi-square test, Fisher's exact test, and student t-test were used as tests of significance (p<0.05 was taken as statistically significant). RESULTS: A total of 1112 patients were diagnosed to have ARF from 1995-2004. The mean age was 37.08 +/- 3.4 yrs. There were 669 (60.1%) males. Medical, obstetric, and surgical causes accounted for 87.6, 8.9, and 3.4 percent of ARF, respectively. Among the medical causes of ARF, acute diarrheal disease was the most common. Other causes of medical ARF included drugs, glomerulonephritis, sepsis, snake bite, leptospirosis, malaria, and copper sulphate, which accounted for 13.4, 9.3, 8.8, 7.8, 7.5, 4.4, and 4.3 percent, respectively. In comparison with the data from 1987-1991, medical ARF remained the most common cause of ARF, though without any statistical significance (87.6 percent vs 89.5 percent, p>0.32). Though surgical ARF had more than doubled from 1.5 percent from 1987-1991 to 3.4 percent (p<0.01) during the present study, it is much less when compared to similar studies in the literature. Obstetric renal failure more or less remained the same (8.9 percent vs 9 percent, p>0.4). A statistically significant decline was noted in overall as well as individual group mortality. The overall mortality declined from 26.4 percent to 19.6 percent (p<0.02). Regarding the outcome of ARF, 611 patients (54.94 percent) showed a total recovery, a partial recovery was noted in 192 patients (17.26 percent), and 91 patients (8.18 percent) had persistent dialysis-dependent renal failure. The factors noted to occur more frequently in the deceased were high entry serum creatinine (>440 micromol), jaundice, sepsis, oliguria, anemia, hypoalbuminemia, and hospital-acquired ARF. The overall requirement of dialysis was 69.0 percent. Hemodialysis was the most common modality of renal replacement therapy. CONCLUSIONS: ARF in South India differs in some important aspects when compared with data from other parts of the country. Significant trend changes were noted with time even within our center. Acute diarrheal disease was the most common cause of ARF. Leptospiral ARF was on the decline, and drugs, sepsis, and malaria were the emerging ARF causes. The incidence of surgical ARF was on the rise. Despite improvements in antenatal care, obstetric renal failure remained a significant cause of ARF. Hemodialysis became the preferred mode of renal replacement therapy.

Enumeration of human knee prostheses--an overview.

Very often clinicians prescribe a limited number or only one type of knee mechanism because it has been found reliable or perhaps specific information on the range and variety of all available mechanisms has not been on hand. The clinician rarely has the opportunity to see all the mechanisms in a common perspective to compare the relative merits of one mechanisms with another. An attempt has been made to enumerate the available human knee-prostheses, both implants and external prostheses, according to their motion. An historical development of knee prosthesis is discussed. A classification procedure is developed for both internal and external prostheses based on their primary functions. The two major classifications in either of these prostheses are monocentric and polycentric mechanisms. A mechanism whose center of rotation does not change through out the range of motion is considered as monocentric mechanism and a mechanism whose center of rotation changes during its operation is considered as polycentric mechanism. The implants are categorized as hinged and non-hinged knee joints. The external prostheses are further classified based on certain primary functions like control in swing phase and/or in stance phase and in extension. The hierarchical classification scheme will benefit kinematicians and designers to analyze the available mechanisms and make necessary improvements. This will also provide a ready-reference to the prosthetists in selecting the best-fit prosthesis from a large family of prostheses.

Synthesis, analysis, and optimization of cam-link prosthetic knee mechanism.

This paper presents the design of three-bar cam-link prosthetic knee mechanism using the instant centers of a natural knee measured experimentally obtained from literature. The cam in this mechanism is approximated as a nth order polynomial form. The instant centers generated by the mechanism are compared with those of the natural knee and the error is minimized using random search optimization techniques. Also, a tangents-merge method is used to develop the cam profile. Normals to the corresponding instant center radii of the cam are found and merged with suitable radii to get a continuous cam profile with no error at prescribed instant centers. The design gives a prosthesis with fewer links and greater accuracy. Results in the form of cam profiles, transmission angles and radius of curvatures are presented.

End-tidal carbon monoxide in newborn infants: observations during the 1st week of life.

Serial end-tidal carbon monoxide corrected for ambient CO (ETCOc) levels were measured in an ethnically diverse population of 87 normal newborn infants during the first 5 days of life. The results demonstrate a progressive reduction in ETCOc from 1.6 +/- 0.4 to 0.8 +/- 0.2 ppm. These levels were unrelated to ethnicity, but were inversely related to serum bilirubin levels. We conclude that ETCOc is not a useful indicator for predicting the course of transitional hyperbilirubinemia in the normal newborn infant.