Growth of lung allografts after experimental transplantation

Heart and lung transplantation has been performed in cases of end-stage cardiopulmonary disease in infants. Nevertheless, it still remains unclear whether lung allografts adjust to a growing organism. In 6 young domestic pigs unilateral left lung allotransplantation was performed. Immunosuppression consisted of a triple drug therapy including cyclosporine, azathioprine, and corticosteroids. Lung growth was studied by using bronchography, pulmonary angiography, and lung histology. After 11 weeks the transplanted animals had doubled their body weight from 24 kg to 48 kg. Non-transplanted animals in contrast doubled their weight within only 6 weeks. The growth retardation was attributed to the immunosuppressive therapy. The bronchial tree and pulmonary vasculature of lung allografts showed a similar growth potential to non-transplanted lungs in animals of equivalent body weight. In one case of recurrent severe rejection of the lung no growth was observed. Therefore it was concluded that lung allografts grow adequately according to the development of the recipient organism. Lung transplantation in children does not seem to be restricted by a limited growth potential of the graft.

Selection and hydroponic growth of bread wheat cultivars for bioregenerative life support systems

As part of the ESA-funded MELiSSA program, the suitability, the growth and the development of four bread wheat cultivars were investigated in hydroponic culture with the aim to incorporate such a cultivation system in an Environmental Control and Life Support System (ECLSS). Wheat plants can fulfill three major functions in space: (a) fixation of CO2 and production of O2, (b) production of grains for human nutrition and (c) production of cleaned water after condensation of the water vapor released from the plants by transpiration. Four spring wheat cultivars (Aletsch, Fiorina, Greina and CH Rubli) were grown hydroponically and compared with respect to growth and grain maturation properties. The height of the plants, the culture duration from germination to harvest, the quantity of water used, the number of fertile and non-fertile tillers as well as the quantity and quality of the grains harvested were considered. Mature grains could be harvested after around 160 days depending on the varieties. It became evident that the nutrient supply is crucial in this context and strongly affects leaf senescence and grain maturation. After a first experiment, the culture conditions were improved for the second experiment (stepwise decrease of EC after flowering, pH adjusted twice a week, less plants per m2) leading to a more favorable harvest (higher grain yield and harvest index). Considerably less green tillers without mature grains were present at harvest time in experiment 2 than in experiment 1. The harvest index for dry matter (including roots) ranged from 0.13 to 0.35 in experiment 1 and from 0.23 to 0.41 in experiment 2 with modified culture conditions. The thousand-grain weight for the four varieties ranged from 30.4 to 36.7 g in experiment 1 and from 33.2 to 39.1 g in experiment 2, while market samples were in the range of 39.4–46.9 g. Calcium levels in grains of the hydroponically grown wheat were similar to those from field-grown wheat, while potassium, magnesium, phosphorus, iron, zinc, copper, manganese and nickel levels tended to be higher in the grains of experimental plants. It remains a challenge for future experiments to further adapt the nutrient supply in order to improve senescence of vegetative plant parts, harvest index and the composition of bread wheat grains.

Influence of postnatally administered glucocorticoids on rat lung growth

Postnatal formation of alveoli can be largely prevented by glucocorticoid treatment, which accelerates alveolar wall thinning and inhibits outgrowth of new interalveolar septa. Since a double capillary network is a prerequisite for interalveolar wall formation, we hypothesized that glucocorticoid treatment inhibited alveolar formation, indirectly, by inducing precocious microvascular maturation. Between 4 and 60 days we followed up qualitatively and quantitatively the effects of 2 weeks (days 2-15) of daily Decadron (Dexamethasone phosphate) injections on the lung structure. Glucocorticoid induced only small changes in body weight or lung volume. However, during the first 2 weeks, it accelerated alveolar wall thinning and microvascular maturation and partly suppressed the outgrowth of new interalveolar septa. In Decadron-treated rats, the interstitial tissue mass was significantly reduced during the first 2 weeks, and a larger alveolar surface area was endowed with a capillary monolayer on days 10 and 13. One week after drug withdrawal, the trend towards precocious maturation of the lung was reversed. Lipofibroblasts reappeared, and inter-airspace septa regressed towards a more immature state. We found indications of a second burst of alveolization by resumption of secondary septa formation. The late sequelae of Decadron treatment (day 60) were manifested as an 'emphysematous' condition of the lungs, with larger and fewer airspaces, the delayed alveolization being insufficient to compensate for the initial deficit.

Growth after Hypophyseal Stalk Transection and Hypophysectomy in Beef Calves

Growth hormone (GH) is a metabolic hormone that plays an important role in long-bone growth and muscle accretion in mammals. The anterior pituitary gland at the base of the brain is the primary site of GH production and release into the general circulation. Neurons in the arcuate nucleus of the hypothalamus in the lower part of the brain secrete GH-releasing hormone ([GHRH] or factor [GRF]) and GH-release-inhibiting hormone ([GHRIH] or somatostatin [SRIH]) that acutely modulate GH secretion by the pituitary gland. The pituitary gland is connected to the median eminence of the hypothalamus by a stalk (hypophyseal stalk). Complete surgical removal of the pituitary gland (hypophysectomy) arrests growth and greatly impairs metabolism in laboratory and farm animal species. Daily subcutaneous injection of bovine GH (bGH) in immature hypophysectomized rats significantly increased body growth and epiphyseal plate width of the long-bone (tibia) compared with diluent-treated hypophysectomized controls. Growth rate was less, however, in the bGH-treated animals compared with intact controls. In beef calves, hypophysectomy completely arrested body weight gain and long-bone growth. GH is secreted in an episodic pattern in young growing intact calves. Episodic GH secretion was abolished immediately following hypophyseal stalk transection, and basal GH blood concentration was less than in shamoperated controls. Regardless, growth continued in these stalk-transected calves during a 1,008-day period, but at a lower growth rate than seen in the sham-operated controls. At autopsy, pituitary gland weight was greatly decreased in hypophyseal stalktransected compared with sham-operated calves. Thus, in spite of obliterated episodic GH release and decreased basal secretion of GH, the isolated pituitary gland of hypophyseal stalk transected calves continues to secrete sufficient amounts of GH for significant growth and development throughout a long period.

Brain Regulation of Growth in Beef Calves

Small peptide hormones produced in the lower part of the brain (hypothalamus) regulate episodic and basal secretion of hormones from the anterior pituitary gland that affect metabolism and growth in cattle. This study focused on long-term growth in young calves subjected to hypophysectomy (HYPOX), hypophyseal stalk transection (HST), and sham operation control (SOC). Crossbred (Hereford x Aberdeen Angus) and Hereford, and Aberdeen Angus calves were HYPOX (n = 5), HST (n = 5), or SOC (n = 8) at 146 days of age, whereas another group was HST (n = 5) or SOC (n = 7) at 273 days of age. Body weight was determined every 21 days from birth to 1008 days of age. From day 146-1008, growth was arrested (P < 0.001) in HYPOX (0.06 kg/day) compared with SOC (0.50 kg/day) calves. Growth continued but at a significantly lower rate (P < 0.05) in calves HST at 146 days (0.32 kg/day) and 273 days (0.32 kg/day) compared with SOC (0.50 kg/day). Although episodic growth hormone (GH) secretion was abolished and peripheral blood serum GH concentration remained consistently lower in HST calves (2.4 ng/ml) than in the SOC (5.5 ng/ml; P < 0.01), the calves continued to grow throughout 1008 days. Peripheral serum thyroid stimulating hormone (TSH) concentration was less (P < 0.05) in HST compared with SOC calves. There was an abrupt decrease (P < 0.001) in serum thyroxine (T4) (4-fold) and triiodothyronine (T3) (3-fold) concentration after surgery that remained to 360 days in HST compared with SOC calves. At sacrifice, pituitary gland weight was markedly reduced (P < 0.001) in HST (0.18 g/100 kg body weight) compared with SOC (0.55 g/100 kg body weight) calves. Histological examination of pituitary glands from HST calves indicated the persistence of secretory GH and TSH cells in the same areas of the anterior pituitary gland as SOC calves. Coronal sections of the gland revealed GH and TSH secreting cells in HST calves that were similar to the controls. These results indicate that long-term growth continues, but at a slower rate, after hypophyseal stalk transection of immature calves in spite of complete abolition of episodic GH secretion and consistently decreased basal secretion of GH, TSH, T4, and T3 compared with sham-operated animals. Growth was abolished after hypophysectomy of immature calves in which circulating GH and TSH was undetectable.

Effects of Novel Growth Hormone Secretagogues on Growth Hormone Secretion in Farm Animals

The requirement for growth hormone (GH) secretion by the anterior pituitary gland in beef calves is demonstrated by a complete lack of long bone-growth and muscle accretion after hypophysectomy (surgical removal of the pituitary gland). When the connecting link (hypophyseal stalk) to the basal region (hypothalamus) of the brain is surgically severed, long bone growth and body weight gain are greatly limited compared with sham-operated controls. This limited growth results from obliteration of episodic GH secretion and reduced basal blood concentration of the hormone compared with sham-operated controls. Thus, the hypophyseal stalk-transected (HST) calf provides an appropriate model to determine mechanisms by which hypothalamic neuropeptides from the brain regulate GH secretion, and thereby growth in the young calf. Neuropeptides have been isolated and characterized in bovine hypothalamus that stimulate GH secretion (GH-releasing hormone [GHRH]) or factor [GHRF] and inhibit GH secretion (GH release-inhibiting hormone [GHRIH] or somatostatin [SRIH]). A dose of .067 micrograms of GHRF per kilogram of body weight injected intravenously in HST calves abruptly increased plasma GH concentration to 55 nanograms per milliliter from the control period mean of 5 nanograms per milliliter. HST calves then were infused intravenously with .033 and .067 microgram somatostatin per kilogram of body weight, during which a pulse injection of .067 microgram of GHRF was administered. GH increase was limited to 9 and 5 micrograms per kilogram body weight during the .033- and .067 microgram SRIH infusions after GHRF; no GH rebound was observed after the SRIH was discontinued. GHRF from humans contains 40 to 44 amino acids. Rat hypothalamic GHRF analogs containing 29 to 32 amino acids elicited dose-dependent GH peak release in these HST calves. In 1977, Bowers and Monomy isolated novel GH releasing peptides consisting of only six amino acids; they caused GH release by isolated pituitary cells in culture and acute GH release when administered intravenously. We recently have utilized a novel nonpeptidyl GH secretagogue of low molecular weight in the pig to determine its mechanisms of action within the central nervous system.

Effects of Bovine Somatotropin and Revalor-S® on Growth Performance and Carcass Leanness in Beef Cattle

Twenty crossbred steers were used to evaluate bovine somatotropin (bST) and an anabolic steroid implant, Revalor-S® (REV), to improve growth and increase carcass leanness. During the first 70 days on feed, bST-treated steers tended to improve live weight gains, consume more feed, and numerically improve feed utilization for growth. The implanted steers grew faster and utilized feed better than steers not implanted with REV. The improvement in gain and feed utilization for growth was maintained throughout the feeding period for REV-implanted steers. At slaughter, REV steers had heavier carcasses which resulted in more pounds of muscle, bone, and fat. When adjusted for hot carcass weight, bST increased leanness of the carcass as evident by the increased weight of the semitendinosus muscle, more pounds of dissected lean, and fewer pounds of dissected fat. Thus, REV and bST can be used to improve growth performance and increase carcass leanness.

Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children

BACKGROUND Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. OBJECTIVES We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). METHODS First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes. RESULTS Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). CONCLUSION Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

The use of second-generation antipsychotics and the changes in physical growth in children and adolescents with perinatally acquired HIV.

Second-generation antipsychotics (SGAs) are increasingly prescribed to treat psychiatric symptoms in pediatric patients infected with HIV. We examined the relationship between prescribed SGAs and physical growth in a cohort of youth with perinatally acquired HIV-1 infection. Pediatric AIDS Clinical Trials Group (PACTG), Protocol 219C (P219C), a multicenter, longitudinal observational study of children and adolescents perinatally exposed to HIV, was conducted from September 2000 until May 2007. The analysis included P219C participants who were perinatally HIV-infected, 3-18 years old, prescribed first SGA for at least 1 month, and had available baseline data prior to starting first SGA. Each participant prescribed an SGA was matched (based on gender, age, Tanner stage, baseline body mass index [BMI] z score) with 1-3 controls without antipsychotic prescriptions. The main outcomes were short-term (approximately 6 months) and long-term (approximately 2 years) changes in BMI z scores from baseline. There were 236 participants in the short-term and 198 in the long-term analysis. In linear regression models, youth with SGA prescriptions had increased BMI z scores relative to youth without antipsychotic prescriptions, for all SGAs (short-term increase = 0.192, p = 0.003; long-term increase = 0.350, p < 0.001), and for risperidone alone (short-term = 0.239, p = 0.002; long-term = 0.360, p = 0.001). Participants receiving both protease inhibitors (PIs) and SGAs showed especially large increases. These findings suggest that growth should be carefully monitored in youth with perinatally acquired HIV who are prescribed SGAs. Future research should investigate the interaction between PIs and SGAs in children and adolescents with perinatally acquired HIV infection.

Molecular mechanisms of prostatic carcinoma growth and progression

Prostate cancer represents the most commonly diagnosed malignancies in American men and is the second leading cause of male cancer deaths. The overall objectives of this research were designed to understand the cellular and molecular mechanisms of prostatic carcinoma growth and progression. This dissertation was divided into two major parts: (1) to clone and characterize soluble factor(s) associated with bone that may mediate prostatic carcinoma growth and progression; (2) to investigate the roles of extracellular matrix in prostatic carcinogenesis.^ The propensity of prostate cancer cells to metastasize to the axial skeleton and the subsequent osteoblastic reactions observed in the bone indicate the possible reciprocal cellular interaction between prostate cancer cells and the bone microenvironment. To understand the molecular and cellular basis of this interaction, I focused on the identification and cloning of soluble factor(s) from bone stromal cells that may exert direct mitogenic action on cultured prostate cells. A novel BPGF-1 gene expressed specifically by bone and male accessory sex organs (prostate, seminal vesicles, and coagulating gland) was identified and cloned.^ The BPGF-1 was identified and cloned from a cDNA expression library prepared from a human bone stromal cell line, MS. The conditioned medium (CM) of this cell line contains mitogenic materials that induce human prostate cancer cell growth both in vivo and in vitro. The cDNA expression library was screened by an antibody prepared against the mitogenic fraction of the CM.^ The cloned BPGF-1 cDNA comprises 3171 nucleotides with a single open reading frame of 1620 nucleotides encoding 540 amino acids. The BPGF-1 gene encodes two transcripts (3.3 and 2.5 kb) with approximately equal intensity in human cells and tissues, but only one transcript (2.5 kb) in rat and mouse tissues. Southern blot analysis of human genomic DNA revealed a single BPGF-1 gene. The BPGF-1 gene is expressed predominantly in bone and seminal vesicles, but at a substantially lower level in prostate. Polyclonal antibodies generated from synthetic peptides that correspond to the nucleotide sequences of the cloned BPGF-1 cDNA reacted with a putative BPGF-1 protein with an apparent molecular weight of 70 kDa. The conditioned media isolated from COS cells transfected with BPGF-1 cDNA stimulated the proliferation and increased the anchorage-independent growth of prostate epithelial cells. These findings led us to hypothesize that BPGF-1 expression in relevant organs, such as prostate, seminal vesicles, and bone, may lead to local prostate cancer growth, metastasis to the seminal vesicles, and subsequently dissemination to the skeleton.^ To assess the importance of extracellular matrix in prostatic carcinogenesis, the role of extracellular matrix in induction of rat prostatic carcinoma growth in vivo was evaluated. NbE-1, a nontumorigenic rat prostatic epithelial cell line, was induced to form carcinoma in athymic nude hosts by coinjecting them with Matrigel and selected extracellular matrix components. Induction of prostatic tumor formation by laminin and collagen IV was inhibited by their respective antibodies. Prostatic epithelial cells cloned from the tumor tissues were found to form tumors in athymic nude hosts in the absence of exogenously added extracellular matrix. These results suggest that extracellular matrix induce irreversibly prostatic epithelial cells that behave distinctively different from the parental prostatic epithelial cell line. ^

THE LONG-TERM GROWTH OF NORMAL HUMAN B CELLS

The feasibility of establishment of continuously proliferating growth factor-dependent human B lymphocytes was investigated. Normal B lymphocytes prepared from peripheral venous blood were stimulated with a variety of known polyclonal B cell activators, in the continuous presence of various cytokine preparations. Continuously proliferating growth factor-dependent B cell populations were obtained from cultures activated with either insoluble anti-IgM ((mu)-chain specific), soluble anti-IgM, heat-killed Staphylococcus aureus Cowen I (SAC), or dextran sulphate (DxS), in the continuous presence of exogenously added growth factor preparations containing either IL-1, IL-2 and BCGF, or BCGF alone. Although growth factor-dependent B cell lines were obtained via all three methods of activation, the correlation of mode of activation and growth factor preparation proved to be critical. B cell lines could not be established with anti-(mu) activation in the presence of only BCGF; however, B cell lines were successfully obtained with SAC or DxS activation from those cultures continuously replenished with only BCGF. These cultured B lymphocyte populations were routinely maintained in logarithmic-phase growth in the presence of exogenously added growth factor, and exhibited a population doubling time of approximately 36 hours. They were shown to specifically absorb BCGF, suggesting the presence of membrane receptors for it. Also, these cultured B cells have been utilized for the development of a microassay for the assessment of a M(,r) 12,000-14,000 B cell growth factor activity that is accurate, sensitive, and precise. The pronounced sensitivity of this bioassay beyond that of the conventional peripheral blood B cell assay has aided in the purification to homogeneity of natural product extracellular BCGF (EC-BCGF), and in the determination of the nucleotide sequence for a gene coding for a protein exhibiting BCGF activity. Additionally, these B cell lines specifically absorb, and proliferate in the presence of, an affinity-purified M(,r) 60,000 trypsin-sensitive intracellular protein derived from freshly isolated human T lymphocytes, providing evidence for a putative intracellular precursor of EC-BCGF, or a novel high molecular weight BCGF species. ^

[The effectiveness of rare earth elements as a possible alternative growth promoter for pigs and poultry].

Mixtures of Rare Earth Elements (REE) have been used as animal growth-promoters on a large scale in China during the last 20 years. Numerous studies carried out in China claim it produces quite sensational growth-promoting effects in all categories of farm animals. To explore the question of whether REE's might prove suitable as a growth-promoter under western keeping conditions, feeding experiments were performed on pigs and poultry. The animals received a typical diet, supplemented with REE salts in concentrations between 75 and 300 mg/kg feed. Weight-gain, feed-intake, feed-conversion and (where applicable) laying parameters were observed. It was shown that in pigs receiving feed supplemented with REEs, an increase in daily weight gain of up to 19% and an improvement in feed-conversion of up to 11% can be achieved, whereas, for poultry, no positive effects on growth or productivity of the animals could be observed. Testing of important organs via Neutron Activating Analysis (NAA) showed a minute accumulation of REE, principally in liver and bones. Analysis of the poultry gut-flora, using selective media, showed that the main microorganism populations of the alimentary canal were unaffected by feed-supplementation with REE.

Bilateral uterine vessel ligation as a model of intrauterine growth restriction in mice

BACKGROUND Intrauterine growth restriction (IUGR) occurs in up to 10% of pregnancies and is considered as a major risk to develop various diseases in adulthood, such as cardiovascular diseases, insulin resistance, hypertension or end stage kidney disease. Several IUGR models have been developed in order to understand the biological processes linked to fetal growth retardation, most of them being rat or mouse models and nutritional models. In order to reproduce altered placental flow, surgical models have also been developed, and among them bilateral uterine ligation has been frequently used. Nevertheless, this model has never been developed in the mouse, although murine tools display multiple advantages for biological research. The aim of this work was therefore to develop a mouse model of bilateral uterine ligation as a surgical model of IUGR. RESULTS In this report, we describe the set up and experimental data obtained from three different protocols (P1, P2, P3) of bilateral uterine vessel ligation in the mouse. Ligation was either performed at the cervical end of each uterine horn (P1) or at the central part of each uterine horn (P2 and P3). Time of surgery was E16 (P1), E17 (P2) or E16.5 (P3). Mortality, maternal weight and abortion parameters were recorded, as well as placentas weights, fetal resorption, viability, fetal weight and size. Results showed that P1 in test animals led to IUGR but was also accompanied with high mortality rate of mothers (50%), low viability of fetuses (8%) and high resorption rate (25%). P2 and P3 improved most of these parameters (decreased mortality and improved pregnancy outcomes; improved fetal viability to 90% and 27%, respectively) nevertheless P2 was not associated to IUGR contrary to P3. Thus P3 experimental conditions enable IUGR with better pregnancy and fetuses outcomes parameters that allow its use in experimental studies. CONCLUSIONS Our results show that bilateral uterine artery ligation according to the protocol we have developed and validated can be used as a surgical mouse model of IUGR.

Growth in Virologically Suppressed HIV Positive Children on Antiretroviral Therapy: Individual and Population-Level References

BACKGROUND Combination antiretroviral therapy (ART) suppresses viral replication in HIV-infected children. The growth of virologically suppressed children on ART has not been well documented. We aimed to develop dynamic reference curves for weight-for-age z scores (WAZ) and height-for-age z scores (HAZ). RESULTS A total of 4,876 children were followed for 7,407 person-years. Analyses were stratified by baseline z-scores and age, which were the most important predictors of growth response. The youngest children showed the most pronounced increase in weight and height initially but catch-up growth stagnated after 1-2 years. Three years after starting ART, WAZ ranged from -2.2 (95% Prediction interval -5.6 to 0.8) in children with baseline age "5 years and z-score "-3 to 0.0 (-2.7 to 2.4) in children with baseline age "2 years and WAZ "-1. For HAZ the corresponding range was -2.3 (-4.9 to 0.3) in children with baseline age"5 years and z-score "-3 to 0.3 (-3.1 to 3.4) in children with baseline age 2-5 years and HAZ "-1. CONCLUSIONS We have developed an online tool to calculate reference trajectories in fully suppressed children. The web application could help to define 'optimal' growth response and identify children with treatment failure.

Cisplatin Nephrotoxicity and Longitudinal Growth in Children With Solid Tumors: A Retrospective Cohort Study

Cisplatin, a major antineoplastic drug used in the treatment of solid tumors, is a known nephrotoxin. This retrospective cohort study evaluated the prevalence and severity of cisplatin nephrotoxicity in 54 children and its impact on height and weight.We recorded the weight, height, serum creatinine, and electrolytes in each cisplatin cycle and after 12 months of treatment. Nephrotoxicity was graded as follows: normal renal function (Grade 0); asymptomatic electrolyte disorders, including an increase in serum creatinine, up to 1.5 times baseline value (Grade 1); need for electrolyte supplementation <3 months and/or increase in serum creatinine 1.5 to 1.9 times from baseline (Grade 2); increase in serum creatinine 2 to 2.9 times from baseline or need for electrolyte supplementation for more than 3 months after treatment completion (Grade 3); and increase in serum creatinine ≥3 times from baseline or renal replacement therapy (Grade 4).Nephrotoxicity was observed in 41 subjects (75.9%). Grade 1 nephrotoxicity was observed in 18 patients (33.3%), Grade 2 in 5 patients (9.2%), and Grade 3 in 18 patients (33.3%). None had Grade 4 nephrotoxicity. Nephrotoxicity patients were younger and received higher cisplatin dose, they also had impairment in longitudinal growth manifested as statistically significant worsening on the height Z Score at 12 months after treatment. We used a multiple logistic regression model using the delta of height Z Score (baseline-12 months) as dependent variable in order to adjust for the main confounder variables such as: germ cell tumor, cisplatin total dose, serum magnesium levels at 12 months, gender, and nephrotoxicity grade. Patients with nephrotoxicity Grade 1 where at higher risk of not growing (OR 5.1, 95% CI 1.07-24.3, P=0.04). The cisplatin total dose had a significant negative relationship with magnesium levels at 12 months (Spearman r=-0.527, P=<0.001).