Short stature and hypothyroidism in a child with Nail-Patella Syndrome. A case report. / Talla baja e hipotiroidismo en un niño con Síndrome de Nail-Patella. Reporte de un caso clínico.

BACKGROUND: Nail-Patella syndrome (NPS) (OMIM: 161200) or hereditary onycho-osteodysplasia is an autosomal dominant disorder characterized by skeletal anomalies, nail dysplasia, renal and ocular abnor malities. The diagnosis is based on clinical and radiological findings and confirmed by the identification of a heterozygous pathogenic variant in the LMX1B gene. Management of these patients involves conti nuous follow-up and treatment ofthe orthopedical, ocular and renal problems that mayoccur. OBJECTIVE: To describe a case of NPS with short stature and hypothyroidism, an association that has not been described in the literature. CASE REPORT: An eleven-year-old boy with a height of 130 cm (-2.01 Stan dard Deviations [SD]) was referred to the Endocrine Unit at the age of 2 years due to altered thyroid tests. At that time, dysplastic nails and disproportionate short stature were detected. Radiological abnormalities initially suggested a skeletal dysplasia. A primary hypothyroidism was confirmed, without anti-thyroid antibodies and with a normal thyroid ultrasound. Levothyroxine treatment was initiated. The diagnosis of NPS was confirmed by a genetic study with a single pathogenic variant in the LMX1B gene. His father presented a similar phenotype with normal stature. His bone age was equivalent to his chronological age. Laboratory screening for short stature and a GH stimulation test were normal. CONCLUSION: We present a child with proven NPS with short stature and hypothyroi dism. We did not find publications that described this triple association. It can't be ruled out that there could be a relationship between NPS and the thyroid alterations found in this patient.

Advanced secretory changes in the proliferative human endometrial epithelium following clomiphene citrate treatment.

In an effort to characterize the effect of clomiphene citrate (CC) on the human endometrium, we took biopsy specimens of the endometrium 24 to 48 hours after CC treatment (100 to 250 mg/day for 5 consecutive days). Nineteen biopsy specimens were taken from 19 patients. Fifteen of the patients suffered from anovulatory infertility associated with oligomenorrhea or normal cycle length. The other four patients were amenorrheic, two in association with hypogonadotropic hypogonadism and two with hypergonadotropic hypogonadism. The histopathology of all samples was evaluated with the use of light microscopy, including periodic acid-Schiff (PAS) and PAS-diastase staining for glycogen demonstration. All samples were also examined with the use of scanning electron microscopy (SEM). Serum levels of estradiol (E2), progesterone (P), luteinizing hormone, and follicle-stimulating hormone were determined on the day of biopsy. In 10 of the 19 biopsy specimens, local or diffuse signs of early secretory events were demonstrated by the presence of subnuclear vacuolization and glycogen in the glandular epithelial cells. SEM corroborated these findings of advanced secretory changes by demonstrating apical protrusions at luminal epithelial cells and secretory products within the glands' openings. The E2 levels ranged between 110 and 1500 pg/ml (mean, 371 pg/ml) and P levels were either undetectable or less than 1.1 ng/ml. The two patients with hypogonadotropic hypogonadism both exhibited the same phenomena; those with primary ovarian failure had atrophic endometrium even after high-dose CC treatment. This observation, together with the low P levels detected, indicating the lack of luteinization, suggests a possible direct effect of CC on the endometrium.(ABSTRACT TRUNCATED AT 250 WORDS)

[Morphological and functional changes of the human vascular endothelial cells in pregnancy induced hypertension patients].

Normal human vascular endothelial cells were cocultured with sera from pregnancy induced hypertension (PIH) patients. After staining it was found that sera from PIH patients could induce stress fibers production from the endothelial cells and which sometime destroy the integrity of normal monolayer structure of endothelium, thus result in endothelial damage. Sera from PIH patients could also induce intracellular adhesion molecules on the cell surface, thus result in the blood cells adhesion to vascular wall, and loss of endothelial cells from vascular wall under certain condition, thereby causing endothelial damage.

Talla baja e hipotiroidismo en un niño con Síndrome de Nail-Patella. Reporte de un caso clínico / Short stature and hypothyroidism in a child with Nail-Patella Syndrome. A case report

Resumen: Introducción: El síndrome de Nail-Patella (NPS) es un desorden autosómico dominante caracterizado por anomalías esqueléticas, displasia ungueal, alteraciones renales y oculares. El diagnóstico se sospecha con la clínica y radiología y se confirma por la identificación de una variante patogénica en el gen LMX1B. El manejo de estos pacientes implica un seguimiento continuo y el tratamiento de las posibles complicaciones ortopédicas, oculares y renales. Objetivo: Describir un caso de NPS con talla baja e hipotiroidismo, asociación que no ha sido descrita en la literatura. Caso clínico: Adolescente de 11 años con talla 130 cm (-2,01 Desviaciones Estándar [DE]) fue referido a Endocrinología a los 2 años de edad por pruebas tiroideas alteradas. Se detectaron uñas displásicas y talla baja despro porcionada, además de anormalidades radiológicas sugerentes de displasia esquelética. Se confirmó hipotiroidismo primario, con anticuerpos negativos y ecografía normal, por lo que se inició trata miento con levotiroxina. El diagnóstico de NPS fue confirmado mediante estudio genético de ADN constatándose una variante patogénica en el gen LMX1B. Su padre presentaba un fenotipo similar, con estatura normal. Su edad ósea era acorde con la cronológica. Tanto el estudio general de talla baja como un test de clonidina para estimulación de GH fueron normales. Conclusión: Presentamos un paciente con NPS confirmado, asociado a talla baja e hipotiroidismo. No hallamos publicaciones en la literatura que describieran esta triple asociación. No se descarta que podría haber una relación entre el NPS y las alteraciones tiroideas halladas en este paciente.

Abstract: Background: Nail-Patella syndrome (NPS) (OMIM: 161200) or hereditary onycho-osteodysplasia is an autosomal dominant disorder characterized by skeletal anomalies, nail dysplasia, renal and ocular abnor malities. The diagnosis is based on clinical and radiological findings and confirmed by the identification of a heterozygous pathogenic variant in the LMX1B gene. Management of these patients involves conti nuous follow-up and treatment ofthe orthopedical, ocular and renal problems that mayoccur. Objective: To describe a case of NPS with short stature and hypothyroidism, an association that has not been described in the literature. Case report: An eleven-year-old boy with a height of 130 cm (-2.01 Stan dard Deviations [SD]) was referred to the Endocrine Unit at the age of 2 years due to altered thyroid tests. At that time, dysplastic nails and disproportionate short stature were detected. Radiological abnormalities initially suggested a skeletal dysplasia. A primary hypothyroidism was confirmed, without anti-thyroid antibodies and with a normal thyroid ultrasound. Levothyroxine treatment was initiated. The diagnosis of NPS was confirmed by a genetic study with a single pathogenic variant in the LMX1B gene. His father presented a similar phenotype with normal stature. His bone age was equivalent to his chronological age. Laboratory screening for short stature and a GH stimulation test were normal. Conclusion: We present a child with proven NPS with short stature and hypothyroi dism. We did not find publications that described this triple association. It can't be ruled out that there could be a relationship between NPS and the thyroid alterations found in this patient.

[Irritation of the anterior nerves of the abdominal wall--Ibrahim syndrome]. / Die Reizung der vorderen Bauchdeckennerven--Ibrahim-Syndrom.

The irritation of the nerves of the anterior abdominal wall (nervi intercostals X-XII) may imitate salpingitis, appendicitis or intraabdominal adhesion. By gentle palpation of the wall of the lower abdomen, spec. in the region of the lateral part of the musculus rectus, the points of pain are to be localized. Xylocaine-injection may give a pain-relieve for a short period of time. Mostly, there must be an operation to loosen adhesions and to dilate the nerve-exits from the lateral part of the musculus rectus.

Renal glomerular and tubular effects of antidiuretic hormone and two antidiuretic hormone analogues in house sparrows (Passer domesticus).

We infused arginine vasotocin, the natural avian antidiuretic hormone, and two antidiuretic hormone analogues into house sparrows (Passer domesticus) to evaluate the vascular and tubular components of antidiuresis in a small (25-g) bird. During control infusion of 25 mmol L-1 NaCl (0.6 mL h-1), urine flow rate was 0.73 mL h-1, glomerular filtration rate was 10.0 mL h-1, the ratio of polyethylene glycol (PEG) in the urine relative to that in the plasma was 16.4, and urine osmolality was 279 mOsmol kg-1. Infusion of arginine vasotocin (0.4 ng kg-1 min-1) decreased urine flow rate by 50% and glomerular filtration rate by 27%, while urine osmolality and the ratio of urine PEG to plasma PEG rose to 150% and 140% of control values, respectively. A higher dose of arginine vasotocin (1.6 ng kg-1 min-1) accentuated these changes. Infusion of the antidiuretic hormone analogue dPTyr(Me)AVT, designed as an antagonist to the V1 (mammalian vascular) receptors for arginine vasopressin, by itself (4.0 ng kg-1 min-1) had no effect on any measured variable (P > or = 0.1). Infusion of the analogue along with arginine vasotocin (0.4 ng kg-1 min-1) abolished the effect of arginine vasotocin on glomerular filtration rate, which suggests that this analogue blocked vascular receptors for arginine vasotocin in house sparrows. Under these circumstances, changes in urine flow rate, the ratio of urine PEG to plasma PEG, and urine osmolality were reduced to nonsignificance. The analogue d(CH2)5[D-Ile2,Ile4,Ala-MH2]AVP, designed as an antagonist to the effects of arginine vasopressin at V2 (mammalian renal tubular) receptors, also was without effect by itself. However, in the presence of this analogue, the effects of arginine vasotocin on urine flow rate and the ratio of urine PEG to plasma PEG were significantly enhanced, and this occurred without any enhanced diminution of glomerular filtration rate. Thus, this analogue appeared to activate a tubular mechanism of antidiuresis. Overall, the data suggest that action of arginine vasotocin at renal vascular receptors plays an important role in effecting antidiuresis in house sparrows. Blockade of renal vascular actions of arginine vasotocin by a V1 antagonist suggest that these receptors may be similar to the mammalian vascular (V1) receptor. The data also suggest a separate action of arginine vasotocin at the renal tubules, but the receptors there apparently differ from the mammalian tubular (V2) receptor.

Effects of the peroxisome proliferator perfluoro-n-decanoic acid on hepatic gluconeogenesis and glycogenesis: a 13C NMR investigation.

Carbon-13 NMR spectroscopy was used to study the effects of the peroxisome proliferator perfluoro-n-decanoic acid (PFDA) on hepatic carbohydrate metabolism in male Fischer-344 rats. The data indicate that PFDA-treated rats display an inhibition in hepatic [1-13C]glucose and [3-13C]alanine utilization on day 5 posttreatment. PFDA rats show hepatic mean glucose and alanine intensities which are significantly greater (ca. 10-100%) than controls. With [1-13C]-glucose as substrate, PFDA rats show severe to complete inhibition in glycogenesis on days 3 and 5 posttreatment. With [3-13C]alanine as substrate, both groups show functional gluconeogenesis and glycogenesis; however, treated rats show a more transient and less intense C1-glycogen resonance relative to control. These data suggest that PFDA inhibits either the hepatocellular transport of glucose and/or its phosphorylation by glucokinase. The effect of PFDA on TCA cycle activity was determined by monitoring the flow of [3-13C]alanine into glutamate. The relative activity of pyruvate carboxylase (PC) versus pyruvate dehydrogenase (PDH) is represented by the ratio of the glutamate NMR signal intensities (C2 + C3)/C4. PFDA rats show a lower (C2 + C3)/C4 glutamate ratio, suggesting greater relative activity of PDH versus PC in PFDA rats relative to controls. Differences in PDH activity may arise from differences in lipolytic activity. Our data suggest a dysfunction in fatty acid metabolism in PFDA rats and corroborate other studies which show that PFDA inhibits fatty acid oxidation.

A comparative toxicological investigation of perfluorocarboxylic acids in rats by fluorine-19 NMR spectroscopy.

Male Fischer-344 rats administered a single intraperitoneal dose of perfluoro-n-octanoic acid (PFOA) or perfluoro-n-decanoic acid (PFDA) display a similar "wasting toxicity" characteristic of perfluorocarboxylic acids, with marked differences in temporal expression. Food/water consumption and urine output were monitored daily in PFOA-treated, PFDA-treated, and control rats. Fluorine-19 nuclear magnetic resonance (NMR) spectroscopy was used to monitor these fluorocarbons and possible fluoro metabolites in vivo, and to correlate differences in elimination with differences in effective toxicity. The data reveal a prolonged hypophagic response to PFDA and a more acute but transient response associated with PFOA treatment. PFOA causes a greater decline in food consumption than PFDA within the first 24 h postdose. PFOA-treated rats also show a ca. 2.5-fold increase in urine output on day 1, with only a slight increase in water consumption. In contrast to PFDA, PFOA-treated rats recover from hypophagia within 8 days. Fluorine-19 NMR spectra of various bodily fluids and liver in vivo display resonances of the parent PFOA or PFDA compounds and do not reveal any evidence of metabolism. Inorganic fluoride from dietary sources is detected in urine from both exposed and control rats. Differences in the route of excretion of PFOA vs PFDA are apparent from the spectral signal-to-noise ratio. The data suggest that PFOA is more readily excreted in the urine while PFDA is preferentially carried in bile. These apparent differences in elimination may account for their observed differences in effective toxicity. The acute transient toxicity and higher LD50 associated with PFOA may result from its rapid renal clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of perfluoro-n-octanoic acid, perfluoro-n-decanoic acid, and clofibrate on hepatic phosphorus metabolism in rats and guinea pigs in vivo.

Phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy was used to study the effects of perfluoro-n-octanoic acid (PFOA), perfluoro-n-decanoic acid (PFDA), and clofibrate (CLOF) on liver phosphorus metabolism in rats and guinea pigs in vivo. All three compounds are known to cause peroxisome proliferation in rats but not in guinea pigs. The data indicate that indices related to overall tissue viability (i.e., adenosine triphosphate levels) remain unaffected at the doses and experimental times investigated for all treatments and both species. PFDA-treated rats revealed a marked increase in a liver phosphomonoester resonance compared with corresponding controls (p < or = 0.01); no such effect was observed in guinea pigs. This particular 31P NMR signal was identified as phosphocholine (PCho) and was found to steadily increase in concentration at consecutive days post-PFDA treatment, reaching 6.26 +/- 0.29 mumol/g liver at 5 days. This is fourfold greater than the PCho levels determined in livers from corresponding pair-fed control rats. The elevation in liver PCho is a specific response of PFDA treatment in rats and is not simply related to peroxisome proliferation in general, since neither PFOA nor CLOF produce such an effect. The data suggest a unique effect of PFDA on liver phospholipid metabolism, specifically phosphatidylcholine, which may involve enhanced phospholipid turnover via phosphatidylcholine-specific phospholipase C activity.

[3-dimensional ultrasonic mammography. Tissue differentiation and tissue-specific breast imaging]. / Dreidimensionale Ultraschallmammographie. Gewebedifferenzierung und gewebespezifische Darstellung der Mamma.

This paper presents first results concerning the three-dimensional ultrasonic data acquisition, the textural analysis of different classes of tissues and the tissue-specific display of mastopathic regions within the female breast, revealing its benefit for diagnosis.

DNA grading of malignancy in breast cancer. Prognostic validity, reproducibility and comparison with other classifications.

The prognostic significance of the "DNA malignancy grade" (DNA-MG) was tested in a series of 104 breast cancer patients in comparison with TNM staging, histomorphologic grading according to Bloom and Richardson, mean nuclear area (MNA) and DNA-histogram classification according to Auer. The reproducibility and representativity of the grading systems were investigated, and their results in primary tumors and lymph node metastases were compared. The scalar DNA-MG was assessed on monolayer smears prepared from paraffin-embedded tissues; the smears were automatically Feulgen stained and used for rapid interactive DNA cytometric evaluation by an automated microscope and a TV image-analysis system. TNM staging showed the highest correlation with survival, followed by histomorphologic grading and DNA-MG; MNA and the DNA-histogram classification failed to give statistically significant prognostic information. Both histomorphologic grading and DNA-MG were identified as parameters adding independent prognostic information to the TNM staging. However, only DNA-MG demonstrated an acceptable reliability, with small 95% ranges between repeated measurements within the primary tumor (+/- 0.3 DNA-MG) and a strong correlation between the results in the primary tumor and its lymph node metastases. These findings show that the DNA-MG is a valid and reliable prognostic index that adds significant prognostic information to TNM staging.

A nuclear magnetic resonance investigation of the upper airways in ferrets. I. Effects of histamine and methacholine.

Alterations induced in the upper airways of ferrets by intranasal provocation with methacholine (MC) and histamine (HS) were monitored using proton magnetic resonance imaging (MRI) and spin-spin relaxation rate (R2) measurements. Both MC and HS cause a significant increase in the MRI signal intensity and a decrease in R2 in the nasal turbinates. A dose-dependent response is observed for 20 to 315 nmol of HS, with a maximum increase in intensity of ca. 50% occurring above 80 nmol. A single unilateral challenge with MC yields a 62 +/- 3% increase in intensity. Control animals (saline-treated) show little change in image intensity. MC and HS cause decreases in the proton R2 by -27.0 +/- 5.5% and -17.2 +/- 4.3%, respectively. These data are indicative of an accumulation of fluid in the nasal airways. MRI provides an effective means to monitor changes in the nasal airways which occur as a result of pharmacological treatment.