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Biomedical subjects

F Santos

Publications and source records attributed to F Santos.

At least 19 recordsLinked to original sources

The effect of growth hormone on the growth failure of chronic renal failure.

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX, n = 40), GH-treated nephrectomized rats (NX+GH, n = 18), sham-operated rats fed ad libitum (SHAMAL, n = 27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF, n = 10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean +/- SEM) 49 +/- 3 and 54 +/- 4 mg/dl, respectively, compared with 16 +/- 4 and 19 +/- 0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0 +/- 3.3 g) and length (3.5 +/- 0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2 +/- 4.0 g, P less than or equal to 0.0001 and 4.1 +/- 0.2 cm, P less than or equal to 0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2 +/- 5.0 g) and length (3.4 +/- 0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81 +/- 2 mg/dl versus 55 +/- 3 mg/dl in SHAMAL (P less than or equal to 0.0001), was not increased in the NX+GH group, 87 +/- 3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.

Animals

Growth hormone secretion from pituitary cells in chronic renal insufficiency.

To examine whether growth hormone (GH) secretion is adversely affected by chronic renal insufficiency (CRI), the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in 5/6 nephrectomized (CRI, N = 18) and sham-operated (N = 18) rats. Two weeks after nephrectomy, during a period of stable uremia, CRI rats had significantly higher serum concentrations (mean +/- SEM) of urea nitrogen and creatinine than sham rats, 16.8 +/- 1.4 mmol/liter (47 +/- 4 mg/dl) and 79.6 +/- 0.0 mumol/liter (0.9 +/- 0.0 mg/dl) versus 6.1 +/- 0.4 mmol/liter (17 +/- 1 mg/dl) and 35.4 +/- 0.0 mumol/liter (0.4 +/- 0.0 mg/dl), respectively (P less than 0.0001). Incremental gains in body weight and nose to tail-tip length of CRI rats over two weeks were also significantly depressed, 53.3 +/- 5.38 g (CRI) versus 87.0 +/- 3.78 g (sham; P less than 0.0001) and 3.2 +/- 0.2 cm (CRI) versus 3.6 +/- 0.1 cm (sham; P less than 0.05). The cumulative food intake as well as food efficiency (g food consumed/g weight gain) were also adversely influenced by the uremic state: food intake 304 +/- 1 g (CRI) versus 397 +/- 6 g (sham; P less than 0.0001) and food efficiency 0.173 +/- 0.013 g/g of weight gain (CRI) versus 0.219 +/- 0.008 g/g of weight gain (sham). No significant difference in GH secretory rate (ng/min/10(7) cells) was found between the uremic and sham animals under basal conditions, 65.2 +/- 2.1 (CRI) and 67.9 +/- 2.2 (sham) or in response to GH-releasing hormone, 282.8 +/- 42.4 (CRI) versus 306.2 +/- 42.6 (sham).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Growth hormone secretory capacity of individual somatotropes in rats with chronic renal insufficiency.

Growth failure is a common consequence of chronic renal insufficiency (CRI) in children and may be due to a number of factors. With regard to growth hormone (GH), regulation is often abnormal in CRI patients. The present study investigated the effect of CRI on the GH secretory responsiveness to GH-releasing hormone in individual rat pituitary somatotropes. Male Sprague-Dawley rats underwent a 5/6 nephrectomy to produce CRI. Control rats (SHAM) received sham operations, which included kidney decapsulation but not removal. Two wk later, during a period of stable uremia, serum creatinine [CRI: 1.1 +/- 0.08 mg/dL (97 +/- 7 mumol/L); SHAM: 0.4 +/- 0.04 mg/dL (35 +/- 4 mumol/L)] and serum urea nitrogen [CRI: 60.7 +/- 8.3 mg/dL (21.7 +/- 3.0 mmol/L); SHAM: 15.8 +/- 1.2 mg/dL (5.6 +/- 0.4 mmol/L)] were significantly elevated in the CRI rats (p less than 0.0005). Weight gain (p less than 0.0005), length gain (p less than 0.0005), food intake (p less than 0.0005), and food efficiency (p less than 0.005) were all significantly lower in the CRI rats. The GH secretory capacity of individual somatotropes was determined using the reverse hemolytic plaque assay technique. Plaque areas were measured to assess relative amounts of GH secreted. The total number of pituitary cells per rat, the percentage of somatotropes, and the mean plaque areas were similar for the two groups. These findings compare favorably with our in vitro study of GH responsiveness in perifused rat pituitary cells under conditions of mild uremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Psychiatric morbidity in general hospital inpatients].

Psychiatric morbidity was studied in 73 patients of three Units (Medicine, Surgery and Obstetrics) of a general hospital (S. Francisco Xavier Hospital, Lisbon). In the first stage, the patients were clinically evaluated by their doctors. In the second stage, psychiatrists using the General Health Questionnaire (G.H.Q. 30) interviewed all the patients according to the clinical evaluation, 41% of the patients had a significant psychological disorder. However, very significant differences were found between the prevalence rates in the three units. As defined by the G.H.Q. 30, 50 patients (68.5%) had psychiatric disorders, which is statistically different from the results obtained through clinical evaluation. The depression and anxiety syndromes were the most frequent disorders. Organic mental disorders were less frequent and almost limited to medical patients. The results of this study confirm a high rate of psychiatric morbidity in the general hospital, although considerable differences exist between the three units included in the study. We can also conclude that many psychiatric disorders are not correctly identified. This fact, more frequent in units where there is a more brief doctor-patient relationship, supports the necessity of implementing liaison psychiatry programs.

Cross-Sectional Studies

Hypercholesterolemia in rats with chronic renal insufficiency not aggravated by recombinant human growth hormone.

The lipid metabolic disorders in chronic renal insufficiency (CRI) are related to increased hepatic lipid synthesis, reduced triglyceride removal coupled with insulin insensitivity and impaired lipoprotein lipase activity. Growth hormone is lipolytic, and the effects of recombinant human growth hormone (rhGH) on the hypercholesterolemia of CRI are unsettled. To test this question, we gave rhGH for 14 days at a dosage of 3 units/day intraperitoneally to two-stage, 5/6 nephrectomized, male Sprague-Dawley rats (n = 18) compared to sex- and age-matched control (n = 27) and CRI (n = 40) rats. At the end of the study, CRI rats and those treated with rhGH had a similar degree of renal impairment, as assessed by serum concentrations (mean +/- SEM) of urea nitrogen (49 +/- 3 vs. 54 +/- 4 mg/dl), creatinine (0.9 +/- 0.0 vs. 1.0 +/- 0.1 mg/dl) and cumulative food intake (311 +/- 8 vs. 290 +/- 12 g). Serum urea nitrogen (16 +/- 4 mg/dl) and creatinine (0.4 +/- 0.1 mg/dl) concentrations as well as food intake (412 +/- 9 g) of control rats were significantly (p < 0.0001) different. Serum cholesterol concentration of CRI rats treated with rhGH (87 +/- 3 mg/dl) was not higher than those of CRI rats (81 +/- 2 mg/dl, p < 0.1338) but was significantly higher than in control rats (55 +/- 3 mg/dl, p < 0.0001). CRI rats treated with rhGH showed a similar serum albumin concentration and lower serum glucose than CRI rats (0.9 +/- 0.1 vs. 0.9 +/- 0.0 g/dl and 144 +/- 4 vs. 163 +/- 3 mg/dl, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[A case of incessant junctional tachycardia in a female patient with aneurysm of the interauricular septum].

A permanent supraventricular tachycardia (SVT) was diagnosed in a 54-year-old hypertensive but cardiologically asymptomatic female patient, admitted to a surgery department for biliary lithiasis and hepatic echinococcosis. Heart rate was about 130 bpm and ECGs showed negative P waves in leads I, II, III, aVF, and precordial leads V2 to V6, being the RP' interval longer than P'R interval. Pharmacological intervention during Holter monitoring (20 hours) was instituted: following i.v. propranolol (4 mg), heart rate progressively decreased (to 112 bpm), mainly due to an increase in SVT RP' interval, and brief, spontaneous SVT interruptions occurred, preceded by P'R interval prolongation; SVT stopped after P' recording, and resumed after 2 sinus beats, (showing enlarged P waves and slightly prolonged PR interval), induced by cycle length shortening; later on, under i.v. amiodarone infusion (100 mg/hour) and coincident with the sleeping period, SVT cycle length progressively increased (to 600 msec), due to equivalent increases in P'R and R'P intervals. Two premature ventricular contractions (PVC) occurred during Holter monitoring at a coupling interval of 80-85% of SVT cycle length (480 msec): one PVC apparently originated in left ventricle lateral wall, captured the atria, which were activated 75 msec earlier than expected; the other PVC, apparently originated in left ventricle septoapical region, did not interfere with SVT cycle length. Before these data, a diagnosis of circus movement tachycardia, incorporating a concealed accessory pathway with slow retrograde conduction and ventricular insertion in the postoroseptal or left posterior paraseptal region, and showing minor impairment of antegrade AV nodal conduction, was made. Invasive electrophysiological study was then discarded. With combined oral antiarrhythmic therapy (amiodarone, 600 mg/d), plus propafenone, 450 mg/d), sinus rhythm was permanently restored, with evidence of intraatrial block, slightly prolonged PR interval and no preexcitation. Transesophageal echocardiography revealed a small atrial septal aneurysm associated with a small atrial septal defect; echocardiographic features were consistent with the hypothesis of incomplete regression of the atrial septal aneurysm after partial closure of the atrial septal defect. Abdominal surgery (cholecystectomy plus partial hepatic pericystectomy) was performed without any complications or SVT recurrences. During a 6-month follow-up period, maintaining amiodarone (200 mg/d) and propafenone (450 mg/d), the patient remained SVT-free, and Holter monitoring performed at 3 and 5 months showed permanent sinus rhythm and 1:1 AV conduction with slightly prolonged PR interval (less than 0.29 sec and shortening at faster heart rates). This case documents Holter monitoring capability for the evaluation of tachycardia mechanisms in patients with permanent SVT.

Amiodarone

Multicystic dysplastic kidney: absence of complications in patients treated conservatively.

The optimal treatment, surgical or conservative, for multicystic dysplastic kidney (MDK) is still undetermined. We analyzed prospectively the evolution of 12 children with MDK who were managed conservatively. After a mean follow-up of 32 months, the only complication found was an episode of urinary tract infection in 3 patients. Complete involution of MDK was observed in 9 patients (75%), the mean period for sonographical disappearance being 16 months. Infants with MDK should be closely monitored and nephrectomy performed when MDK compresses neighbor organs or hypertension develops. There is no agreement on the best therapeutic approach in patients in whom MDK involution has not occurred after a prudential waiting time still not determined.

Female

Blood mononuclear cells from patients with severe congenital neutropenia are capable of producing granulocyte colony-stimulating factor.

Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia or absence of blood neutrophils secondary to a maturational arrest at the level of promyelocytes. We examined peripheral blood mononuclear cells (PBMC) of SCN patients who demonstrated normalization of their blood neutrophil counts in a phase II clinical study with recombinant human granulocyte colony-stimulating factor (rhG-CSF). When stimulated in vitro with bacterial lipopolysaccharides (LPS), PBMC of those SCN patients produced G-CSF activity, as judged by proliferation induction of the murine leukemia cell line, NFS-60. Western and Northern blot analysis showed G-CSF protein and G-CSF-mRNA indistinguishable in size from those of normal controls. We conclude that PBMC of the SCN patients tested are capable of synthesizing and secreting biologically active G-CSF in vitro.

Adult

The syndrome of renal tubular acidosis and nerve deafness. Discordant manifestations in dizygotic twin brothers.

The syndrome of renal tubular acidosis (RTA) and nerve deafness is a distinct nosological entity that is inherited as an autosomal recessive trait. We studied a pair of dizygotic twin brothers both with nerve deafness but only one with RTA. Distal RTA was diagnosed in twin A because of inappropriately high urinary pH (6.9) and low net acid excretion (40.0 muEq/min per 1.73 m2) in the presence of hyperchloraemic metablic acidosis, and fractional bicarbonate excretion of 1.6% at a normal serum bicarbonate concentration. The urine minus blood PCO2 differences (U-B PCO2) during a neutral sodium phosphate load and in alkaline urine induced by bicarbonate supplementation were: 11 and 0 mm Hg, respectively. Twin A developed nephrocalcinosis and, after a 9.5-year follow-up period, was 5.3 cm taller than his brother. Twin B remained asymptomatic. Periodic determinations of blood pH and serum bicarbonate were normal and urine pH decreased to 4.6 in the face of ammonium chloride-induced metabolic acidosis. The U-B PCO2 assessed in alkaline urine was 33.5 mm Hg. Audiograms demonstrated bilateral nerve deafness in both brothers. The presence of deafness without RTA has not been previously reported in this syndrome. This report also shows that a primary distal acidification defect is responsible for the RTA observed in this syndrome.

Acidosis, Renal Tubular

Cortisone effects on growth, food efficiency, and in vitro growth hormone release.

These studies were designed to investigate the cause of growth retardation during glucocorticoid treatment in rats. In young animals, body weights and amounts of food consumed were measured at two-day intervals, beginning at 29 days of age. Average food intake and food efficiency were calculated. Animals were treated with cortisone (CORT, 5 mg/rat/day, s.c.) or saline (SAL) for eight days between 37 and 44 days. Growth hormone (GH) release by dispersed pituitary cells in response to nine concentrations of GH-releasing hormone (GHRH) were tested by in vitro perifusion at 45 and 73 days. As previously shown, CORT caused a cessation of growth during the treatment period, and body weight failed to catch up. Food efficiency was decreased during CORT treatment. All parameters of in vitro GH release including basal GH secretory rate, overall GH response to GHRH, and the GHRH concentration-response curves were significantly increased by CORT in the 45-day-old animals. An age-related increase in GH release was also observed between the 45 and 73 day saline-treated animals. These results support the hypothesis that glucocorticoids inhibit growth by induction of changes in food metabolism and GH secretion. The effect on the pituitary gland itself paradoxically involves an increase in GH secretory capacity in response to GHRH.

Animal Nutritional Physiological Phenomena

In vitro ketotifen protection in bronchial hyperreactivity.

There are drugs, such as ketotifen, that inhibit bronchospasm through different mechanisms. In this study, we looked at the changes in the number of sanguineous cells that ketotifen produces, especially in basophil cells, that could explain its prophylactic effects in bronchial hyperreactivity disclosed by exercise, as well as its relation to the variations in basal and total histamine in blood. 22 patients were selected, with a diagnosis of extrinsic bronchial asthma with sensitization against Dermatophagoides, and were compared to a control group. They all underwent an exercise test. Blood samples were taken before and after exercise in order to measure the number of leukocytes and the changes in basal and total histamine. We found that the number of basophils does not increase after exercise in untreated patients, while it does in the control group and in treated patients. This implies that ketotifen stabilizes the basophil cells, hindering their degranulation and the subsequent liberation of mediators that would produce bronchospasm after exercise.

Adolescent

Growth hormone metabolism in uremia.

The influence of chronic renal failure (CRF) on growth hormone (GH) and insulin-like growth factor I (IGF-I) metabolisms is not well understood. Clinical studies on GH secretion in CRF have yielded conflicting results. In vitro, pituitary GH secretion has been shown to be unimpaired in moderate uremia. CRF reduces binding of GH to liver as a result of decreased number of GH receptors. CRF induces elevation of serum GH concentrations and does not modify the circulating values of IGF-I. However, the somatomedin bioactivity of uremic serum is depressed, and unsaturated low-molecular-weight IGF-I-binding proteins have been suggested to act as inhibitory factors of IGF-I action. Circulating GH and IGF-I do not necessarily reflect the state of GH and IGF-I in tissues, and further investigations on the effect of CRF on GH and IGF-I metabolisms at the growth plate level are clearly required.

Child

Renal cell carcinoma in childhood.

Renal cell carcinoma is extremely infrequent in children. We report a case of renal cell carcinoma in a 13-year-old male. Presenting manifestations were loin pain, fever, and weight loss. A palpable abdominal mass was found. Imaging studies showed a solid mass into the right kidney. Nephrectomy was performed and pathological examination demonstrated characteristic findings of renal cell carcinoma. This report emphasizes that renal cell carcinoma should be included in the differential diagnosis of renal masses in children.

Adolescent