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Biomedical subjects

L Marin

Publications and source records attributed to L Marin.

At least 55 records · Page 3Linked to original sources

1,25-dihydroxyvitamin D3 receptors in rat lung during the perinatal period: regulation and immunohistochemical localization.

We have previously reported that in contrast to what has been described in adult lung, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has specific binding sites in rat fetal lung at the end of gestation, and it stimulates in vitro the phospholipid biosynthesis and surfactant release from fetal rat type II pneumocytes. In the present study an immunohistochemical technique using a rat monoclonal antibody (9A7 gamma) and binding studies were carried out on fresh lung tissues from fetal and newborn rats during the perinatal period to identify the cell(s) directly responsive to 1,25-(OH)2D3 in fetal lung and to look for a down-regulation of the 1,25-(OH)2D3 receptors in the perinatal period. We also searched for a regulation of 1,25-(OH)2D3 binding to fetal lung by 1,25-(OH)2D3 itself and by factors known to affect lung maturation or be involved in parturition. Our results suggest that 1) fetal type II pneumocytes are target cells for 1,25-(OH)2D3; 2) a physiological down-regulation of the 1,25-(OH)2D3 receptors in rat lung occurs in the perinatal period, starting a few hours before birth and lasting at least up to the fifth day of life; and 3) the capacity of rat fetal lung to bind 1,25-(OH)2D3 can be modulated in vitro by different hormones; a small inhibitory effect is observed with oxytocin (100 microU/ml), while PRL (10(-8) M), T4 (10(-6)-10(-10) M), 1,25-(OH)2D3 (10(-9)-10(-10) M), and, to a lesser extent, dexamethasone (10(-7) M) induce a 2- to 4-fold increase in the number of 1,25-(OH)2D3 receptors without altering the binding affinity of receptor for 1,25-(OH)2D3.

Animals↗

Synaptic restructuring during long-term facilitation at the crayfish neuromuscular junction.

Long-term facilitation was induced by 20-Hz stimulation of the motor axon innervating the opener muscle of the crayfish, Procambarus clarkii. Excitatory postsynaptic potentials remained potentiated for several hours after stimulation. Structural correlates of potentiation were sought. Nerve terminals of the motor axon were fixed for electron microscopy in unstimulated preparations (controls), and during and after 20-Hz stimulation. Synapses were reconstructed from micrographs obtained from serial sections. Synaptic contact area and the number of vesicles at the presynaptic membrane did not change after 20-Hz stimulation, but the latter decreased during stimulation. Presynaptic dense bars ("active zones") decreased in number during and increased after stimulation, while perforated synapses increased after stimulation. Modification of presynaptic structures occurs rapidly and may be linked to long-lasting changes in quantal content of transmission.

Animals↗

Effects of the antiglucocorticoid RU 486 on the maturation of fetal rat lung surfactant.

The role of endogenous glucocorticoids in the control of surfactant system maturation was investigated in the fetal rat using an antiglucocorticoid molecule synthesized by Roussel-UCLAF, RU 486. The drug was administered to the mother from day 16 of gestation on. In a preliminary step, the transplacental transfer of RU 486 and its antiglucocorticoid effects on fetal target tissues were verified by evidencing RU 486-receptor complexes in fetal liver and lung, by measuring liver glycogen content, and by evaluating fetal blood corticosterone. The maturational state of fetal lungs was assessed biochemically on days 19, 20, and 21 of gestation by measuring their glycogen content, the phospholipid content of whole lung tissue and isolated surfactant fraction, and the incorporation of [methyl-3H]choline into DSPC. Morphological development was studied by analyzing electron micrographs of type II cells. The measured parameters clearly indicated a slowing of maturational processes in lungs of fetuses from RU 486-treated mothers, thereby demonstrating that endogenous glucocorticoids are actually involved in the control of lung maturation. In addition, the obtained results showed that endogenous corticosteroids specifically acted on the surfactant system of the fetal lung.

Animals↗

Salt and water homeostasis during oral rehydration therapy in neonates and young infants with acute diarrhoea. II. Rehydration with a solution containing 90 mmol sodium per litre (ORS90).

The clinical response and changes in water and salt homeostasis were studied during oral rehydration therapy (ORT) with a solution containing 90 mmol sodium per 1 (ORS90) in 9 infants less than 2 months old (range 2-60 days). Two infants were still dehydrated 36 hours after starting ORT and were excluded from the study. Fluid was retained more rapidly and also to a larger extent than in infants of the same age treated with a solution with a sodium concentration of 60 mmol/l (ORS60). The stool sodium output was higher than that found previously in infants of the same age treated with ORS60. We conclude that during ORT the gut plays an active role in the regulation of salt homeostasis. When the sodium intake is high the percentage of sodium remaining unabsorbed is higher than when the intake is low. This mechanism reduces the risk of hypernatremia in young infants treated with ORS90. The study thus demonstrates that ORS90 is effective and also seems to be safe in the treatment of neonates and young infants with dehydration secondary to diarrhoea if fluid intake is kept around 200 ml/kg/day during the rehydration period.

Acute Disease↗

Optimization of fetal lung organ culture for surfactant biosynthesis.

Lung organ culture has been a widely used system for studying differentiation and maturation of alveolar epithelium through various culture conditions. The purpose of this work was to carefully characterize in vitro lung biochemical differentiation through isolation of surfactant fraction from tissue and to search for optimal culture conditions. Fetal rat lung was explanted on the 18th gestational day for studying glycogen storage, and on the 20th gestational day for studying surfactant accretion, and cultivated for 48 h. Morphologic differentiation was studied by electron microscopy on tissue explanted on the 17th or 18th gestational days and cultivated for various times. Glycogen storage was greater on fluid medium, although less than occurring in vivo. Cellular integrity and surfactant accumulation were maximal on a semisolid medium containing 0.5% agar. Use of O2-CO2 instead of air-CO2 for gassing the explants slightly decreased phospholipid accumulation. Among media used in previous lung culture studies, Waymouth MB 752/1 was the only one to allow net glycogen accumulation in vitro. The most favorable media for surfactant phospholipid accretion were Waymouth MB 752/1, Eagle's minimum essential and its Dulbecco's modification, CMRL 1066, and NCTC 109. They allowed a 12- to 14-fold increase of surfactant fraction phospholipids in vitro, which is similar to the increase occurring in vivo during the same period. Ham's F10 and F12 media allowed a six fold increase. RPMI 1640 and medium 199 (M199) allowed only a three fold increase. Phospholipid concentration in nonsurfactant fraction only doubled during culture, and differences between various media were much less marked. DNA concentration changed little during culture. Morphologic differentiation of epithelial cells was advanced as compared with in vivo timing in a medium allowing maximal surfactant accretion (Waymouth MB 752/1) but not in a medium allowing low surfactant increase (RPMI 1640). The possible role of compositional differences between media is discussed.

Animals↗

Focal labeling of axonal terminals with active synapses recorded by an extracellular macro-patch electrode.

A technique to label active synaptic terminals, whose electrophysiology had been monitored by a macro-patch electrode, was developed for a crustacean neuromuscular preparation. The active synaptic terminals were labeled by release-dependent uptake of horseradish peroxidase (HRP) into synaptic vesicles. The focal labeling technique involved the following steps: (1) locating a site where evoked synaptic currents could be recorded at a subset of neuromuscular synapses by a macro-patch electrode; (2) reducing synaptic transmission by bathing the preparation in a solution containing low [Ca2+] and high [Mg2+]; (3) introducing HRP as an extracellular marker into the solution bathing the preparation; (4) restoring synaptic release focally by ejection of a solution containing Ca2+ from the macro-patch electrode. The muscle fibre with labeled synapses was fixed for electron microscopy and processed for HRP histochemistry. The distribution of HRP-labeled vesicles was documented by electron microscopy and semi-serial sectioning. A significant increase in labeled vesicles was found within a maximum radius of 10-15 micron from the lumen of the macro-path electrode. This maximum radius of labeling set an upper limit to the number of active synapses recorded by the macro-patch electrode.

Animals↗

The indications for total cutaneous electron beam radiation therapy of mycosis fungoides.

From 1977 to 1984, we treated 34 patients with mycosis fungoides and 9 patients with B cutaneous lymphomas. Eighteen patients with mycosis fungoides were treated with total skin electron irradiation (TSEI) and had a minimum follow-up of 15 months (range 15 months to 7 years). The lowest electron energy of the linear accelerator was 8 MeV therefore we placed a plexiglas screen between the patient and the machine; the resulting electron energy was 4 MeV. The total dose was 30 Gy delivered in 12 fractions over 40 days. There were 8 males and 10 females. The median age was 48 years (ranging from 13 to 78 years). All patients were staged as follows: Stage A = superficial lesions covering less than 50% of the body surface; Stage B = superficial lesions covering more than 50% of the body surface; Stage C = tumors involving the skin, lymph nodes and/or visceral organs. Five patients with Stage A (5/5) and 5 patients with Stage B (5/5) had a complete remission, 1 stage A patient relapsed 6 months after completion of treatment. All the Stage B patients recurred between 3 and 15 months. The recurrences were localized to the skin and were well controlled with topical nitrogen mustard or puvatherapy. Among the Stage C patients, 3 did not respond to treatment and died of their disease; the remaining 5 patients achieved complete remission but they all relapsed from 2 to 9 months following completion of treatment. The median follow-up was 32 months and the average time for relapse was 6.5 months. All relapses except one (15 months) occurred within the first year. We feel that total skin electron irradiation is indicated in Stage A and B patients. However, we feel Stage C patients should receive TSEI for palliative purposes only.

Adolescent↗

Definitive radiation treatment for early stage carcinoma of the soft palate and uvula: the indications for iridium 192 implantation.

From 1971 to 1984 59 T1 and T2 carcinomas of the soft palate and uvula were treated definitively by irradiation at the Henri Mondor hospital. Included are ten patients previously irradiated to the oropharyngeal area for either a carcinoma of the soft palate or another malignancy. Sixteen patients were treated by external irradiation alone, 14 by Iridium 192 implantation, and 29 by a combination of the two. Two techniques of implantation were used: the guide gutter technique (33 patients) and the plastic tube technique (10 patients). Clinically negative neck nodes (51/59) either received prophylactic telecobalt therapy (39/51) or were surveilled (12/51). Clinically involved nodes (8/59) were managed either by external irradiation alone (4/8) or combined with neck dissection (4/8). Local failure was 25% (4/16) after exclusive telecobalt therapy, 18% (5/19) after combined telecobalt therapy and implantation, and 0% (0/14) after Iridium 192 implantation alone. No local failures were seen with the plastic tube technique (0/10) as compared to 15% (5/33) for guide gutters. Only two nodal failures were observed (2/59: 3%). Crude 5-year disease-free survival was 33%. Severe complications were limited to one osteonecrosis, one soft tissue necrosis, and one partial palatal incompetence. Salivary impairment was reduced when implantation was used for part or all of the treatment. We recommend 45 Gy external radiation followed by 30 Gy from Iridium 192 implantation using the plastic tube method unless there has been prior oropharyngeal irradiation, in which case we give 60 Gy from implantation alone. For clinically negative neck nodes, we recommend 45 Gy prophylactic external neck irradiation. For clinically positive lymph nodes, this should be followed by either a 25 to 30 Gy boost to the involved nodes or a neck dissection.

Brachytherapy↗

Oral rehydration therapy in neonates and young infants with infectious diarrhoea.

The clinical response and changes in water and salt homeostasis during ORT was studied in 15 infants less than 2 months old (range 2-50 days) with acute diarrhoea. Eight patients were neonates and 7 were 1-2 months old. The oral rehydration solution contained 60 mmol sodium per litre. All patients except one were successfully rehydrated. The fluid retention was significantly higher in neonates and young infants than in infants above 3 months of age treated in the same way. One patient in the group of neonates who had a normal sodium level on admission developed hypernatremia with a sodium level of 162 mmol/l 36 hours after the start of ORT. The urinary sodium excretion was lower in the neonates than in the young infants. The results show that neonates and young infants have a lower capacity than older infants to excrete water and salt and therefore run a great risk of developing fluid and salt retention during ORT. The risk is most pronounced in neonates who, due to immaturity of the renal function, are unable to excrete excess fluid and salt.

Acute Disease↗

Lung maturation in the hyperinsulinemic rat fetus.

Hyperinsulinemic rat fetuses were obtained either by repeated in utero injections of long-acting insulin (resulting in fetal hypoglycemia) or by chronically infusing intravenous glucose to the mother (resulting in fetal hyperglycemia). Fetuses were examined at term. In insulin-injected fetuses (n = 15), surfactant (S) fraction phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) were significantly decreased (3.6 +/- 0.1 nmol Pi/mg tissue; p less than 0.001 and 2.8 +/- 0.1 nmol/mg; p less than 0.025, respectively) as compared with their saline-injected controls (4.8 +/- 0.2 and 3.3 +/- 0.1 nmol/mg, respectively, n = 19). However, residual (R) fraction was unchanged, and there was no difference in whole-lung phospholipids (combined S and R fractions). These results are consistent with morphological data showing a lower lamellar body area per type II cell profile in insulin-injected fetuses as compared with their controls [1.41 +/- 0.13 micron 2 (n = 72) versus 1.99 +/- 0.14 micron 2 (n = 129) p less than 0.01]. Glycogen content was slightly higher in insulin-injected fetuses (18.5 +/- 1.0 micrograms/mg, n = 17) than in their controls (15.1 +/- 0.8 micrograms/mg, n = 18; p less than 0.05). In the second model, changes in S fraction PC and DSPC were similar to those observed after insulin-injections: 4.3 +/- 0.25 and 3.4 +/- 0.2 nmol Pi/mg in fetuses of glucose-infused rats (n = 10) versus 5.7 +/- 0.45 and 4.3 +/- 0.3 nmol Pi/mg, respectively, in controls (n = 10, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Radiation therapy for carcinoma of the pinna using iridium 192 wires: a series of 70 patients.

From January 1970 to November 1982, 70 patients with carcinoma of the pinna were treated by interstitial irradiation. An afterloading technique with Iridium 192 wires was used. One patient recurred and had a total pinnectomy followed by 60 Gy external radiation. This patient was alive without evidence of disease at 134 months. Three patients who had tumors greater than 4 cm in size at presentation developed late necrosis which required subsequent total pinnectomy. Cosmetic results were assessed in 55 patients and were good with few late sequelae (in 78% of cases (36/46) when the tumor measured less than 4 cm, but only in 1/9 when the tumor measured more than 4 cm). We advocate interstitial Iridium 192 irradiation for treatment of pinna tumors smaller than 4 cm. None of 39 patients with squamous cell carcinoma had biopsy proven cervical lymph node metastasis at the time of diagnosis. Four patients with squamous cell carcinoma (4/39: 10%) later developed a regional nodal metastasis after treatment of the pinna. All four relapsed in the parotid region and were managed by partial parotidectomy and neck dissection followed by external irradiation. One of these four patients died from uncontrolled cervical node disease. In our opinion, when regular follow-up is dependable, it is reasonable to save treatment of the cervical nodes for those patients who relapse with involved metastatic cervical nodes.

Adult↗

The past and future of conservative treatment of breast cancer.

Since 1961 more than 1,200 patients with breast cancer were treated conservatively at the Institut Gustave Roussy (Villejuif) and, since 1970, at the Hôpital Henri Mondor (Créteil). This group included approximately 25% T1 tumors, 55% T2 tumors, and 20% T3 tumors. All of these patients were staged, according to the U.I.C.C. Tumor Classification System. This paper presents the results of treatment of 330 patients who were followed for a minimum of 10 years and 59 patients who were followed for a minimum of 15 years. We also present our most recent protocol, which has been in use since 1983.

Breast Neoplasms↗

Oral rehydration therapy in malnourished infants with infectious diarrhoea.

The clinical response and changes in water and salt homeostasis was studied for 36 hours during oral rehydration therapy with a rehydration solution containing 60 mmol sodium/l (ORS60) in 14 malnourished 3- to 15-month-old Turkish infants with acute infectious diarrhoea. All patients were successfully rehydrated with this treatment. Sodium was efficiently absorbed from the gut and water balance was rapidly restored. Because of excess fluid retention following the initial rehydration period about 50% of the patients became oedematous. Urine volume and urinary sodium excretion were found to be much lower than in well-nourished patients of the same age with acute diarrhoea who were treated in the same way. In all of the malnourished infants the serum sodium level remained within the normal range during treatment. The results show that malnourished infants retain much more fluid and sodium than infants who are in a normal nutritional state. Excessive retention of water and salt seem to be due to an inability of the kidneys to control sodium and fluid homeostasis while orally administered sodium and fluid are being absorbed from the gut. The results show that ORT is safe and efficient in the treatment of malnourished infants with acute diarrhoea. But since these infants run a high risk of developing a severe retention of fluid and salt, and consequently may develop circulatory failure due to hypervolaemia during oral rehydration therapy, it is important to carefully monitor the volume of fluid that is given.

Administration, Oral↗

Morphological transformation of synaptic terminals of a phasic motoneuron by long-term tonic stimulation.

In vivo stimulation of a relatively "silent" phasic crayfish motoneuron changes the ultrastructure of its synaptic terminals to a more tonic phenotype. The closer muscle of the crayfish claw is supplied by only 2 excitatory motoneurons, one of which is phasic and the other tonic. The ultrastructures of conditioned phasic, unconditioned phasic, and tonic motor terminals were compared. The terminals of the tonic motor axon were larger in cross-sectional area, had larger mitochondria, greater synaptic contact area, and were more varicose than unconditioned phasic terminals. Following long-term tonic stimulation of the phasic axon, its terminals became more varicose, mitochondrial cross-sectional area more than doubled, and synapses and mitochondria came into closer proximity, although mean terminal cross-sectional area did not change. Thus, the conditioned phasic terminals became more similar to those of the tonic motor axon. These changes in ultrastructure correlate with, and may be causally linked to, previously reported changes in neuromuscular synaptic physiology produced by in vivo tonic stimulation of this motoneuron. We conclude that the ongoing level of impulse activity can affect the ultrastructural differentiation of synaptic terminals and synapses of the phasic motoneuron.

Animals↗

Unsuccessful oral rehydration therapy in an infant with enteropathogenic E. coli diarrhoea. Studies of fluid and electrolyte homeostasis.

A 4-month-old male infant with severe hyponatremic dehydration due to an enteropathogenic E. coli O125: B15-induced diarrhoea had continued very high stool fluid output with a very elevated sodium concentration after hospitalization and the institution of oral rehydration therapy (ORT). Thirty-six hours after start of ORT intravenous therapy was required. The results of studies of fluid and salt homeostasis in this patient have been compared with those obtained in 3 other patients who had acute diarrhoea of the same severity but caused by another strain of enteropathogenic E. coli (O111:B14) and who were successfully treated with ORT. On ORT the patient with treatment failure had a stool volume which was almost 8 times larger and a stool sodium output which was about 5 times higher than in the successfully treated patients. During the 36-hour-period of ORT fluid losses were about the same as the fluid intake. The results as regards urinary fractional sodium excretion and the urinary potassium/sodium quotient indicate that the severe sodium depletion which was present on admission in the unsuccessfully treated patient persisted during ORT. The reason for ORT failure may be that the infectious E. coli strain had bacilli-adherent qualities that cause damage of microvilli.

Dehydration↗

Oral rehydration therapy in infectious diarrhoea. Comparison of rehydration solutions with 60 and 90 mmol sodium per litre.

The clinical response and changes in water and salt homeostasis as judged from serum sodium levels, salt and water retention and renal handling of sodium was studied during 36 hours following the start of oral rehydration therapy (ORT) with a solution containing 60 mmol Na/l (ORS60) in 17 well-nourished, moderately dehydrated Turkish infants aged 3 to 15 months who had acute infectious diarrhoea (7 with rotavirus, 3 with enteropathogenic E. coli 0 111: B 84, and one with enteropathogenic E. coli 0 125: B 15, one with salmonella and 5 of unknown etiology. In the successfully treated patients sodium and water balance was normalized within 36 hours. In the cases with hypernatremic dehydration the serum sodium concentration rapidly became normal. The results were compared with those obtained in a previous study of the same type of patients who were rehydrated with a solution containing 90 mmol Na/l (ORS90). Although retention was considered to be satisfactory after ORS60 it was less than after ORS90. The changes in the fractionary urinary sodium excretion and the potassium sodium quotient in the urine indicated a less rapid normalization after ORS60 than after ORS90.

Administration, Oral↗

Maturation of fetal rat lung in diabetic pregnancies of graduated severity.

Biochemical and morphologic maturation of fetal rat lung was studied in pregnant, diabetic rats with different levels of glucose intolerance (sub-, mildly, and severely diabetic). Fetuses were almost normoglycemic and hyperinsulinemic in subdiabetic rats, both hyperglycemic and hyperinsulinemic in mildly diabetic rats, and hyperglycemic but hypoinsulinemic in severely diabetic rats. A similar delay in type II pneumocyte differentiation and a similar decrease of disaturated phosphatidylcholine (DSPC) content in lung tissue and broncho-alveolar material recovered by lung lavage occurred in the fetuses of the three diabetic groups, independently of the severity of diabetes. Phosphatidylglycerol (PG) was decreased in fetuses from severely diabetic rats only. DSPC appeared specifically affected in fetuses of sub- and mildly diabetic groups, whereas in those of severely diabetic groups, DSPC alterations accompanied a variety of abnormalities including whole lung hypoplasia and hypotrophy and decreases of sphingomyelin, unsaturated PC, and lysoPC. The mechanisms leading to abnormal lung development could therefore be different in fetuses of sub- and mildly diabetic rats on one hand and fetuses of severely diabetic rats on the other. Since hyperinsulinemia was the prominent feature of fetal "milieu intérieur" in subdiabetic rats, this study presents arguments gained from in vivo experiments for an implication of hyperinsulinemia in lung developmental retardation due to maternal diabetes. However, the decrease of PG seems to depend on increased blood glucose level in itself. Diminished lung glycogen breakdown and decreased lung triglyceride content, more pronounced in fetuses of sub- and mildly diabetic rats than in those of severely diabetic rats, suggest that in the former, the decrease of DSPC biosynthesis could be due to decreased availability of substrates because of abnormal glycogen utilization. Fetuses from sub- and mildly diabetic rats constitute experimental models most closely resembling the human fetus of the diabetic mother with respect to circulating glucose and insulin. They appear therefore more adequate for elucidating the mechanisms of abnormal lung development in the diabetic pregnancy. In contrast, fetuses from severely diabetic rats associate very high blood glucose levels and hypoinsulinemia, which are features closer to those of adult diabetic subjects than to those of the human fetus of the diabetic mother.

3-Hydroxybutyric Acid↗