Screening for silent myocardial ischemia in diabetic patients.
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Biomedical subjects
Publications and source records attributed to M Harter.
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We have previously shown that low-density (LDL) and high-density (HDL) lipoprotein from healthy subjects can promote in vitro prostaglandin (PG) release by murine macrophages. In this pilot study, we have measured PG production induced by lipoproteins of six diabetic patients with poor metabolic control, compared to five healthy controls. Plasma lipoprotein levels were similar in both groups. Lipoprotein fractions were purified by sequential ultracentrifugation. After lipoprotein incubation with cells, supernatants were extracted and PG quantified by HPLC. In presence of LDL, in control subjects, there was an increase in total PG production, mainly due to thromboxane B2 (TxB2). In diabetic patients, the secretion pattern was similar. In presence of HDL, in control subjects, total PG secretion was also increased, but it was balanced between TxB2 and prostacyclin. In diabetic patients, at low HDL concentration (10 mg/l) the secretion was mainly due to TxB2, while at higher HDL concentrations (100 mg/l). the secretion was balanced between TxB2 and prostacyclin. Comparison of means of areas under curve for the two groups studied showed that LDL increased all PG secretion in diabetic patients compared to controls (P < 0.05 for PGF2alpha), while HDL increased all PG secretion in controls compared to diabetic patients, except PGF2alpha. Our work suggests a key role of LDL in TxB2 secretion in diabetic patients, which is a major proaggregant and vasoconstrictive agent. There was also an increased secretion of all PG in diabetic patients.
Subacute thyroiditis usually recovers completely, and recurrences are unfrequent. We report hereafter the case of a 70-year-old man with a typical diagnosis of subacute thyroiditis. He reported a similar episode 20 years earlier, followed by a mild but persistant hypothyroidism. This case reminds that recurrence of subacute thyroiditis can occur even after many years.
Autoimmunity may be involved in idiopathic premature ovarian failure (POF). However, the frequency, physiopathology and potential reversibility of autoimmune oophoritis needs clarification. Using an ELISA against whole tissue homogenate as antigen, from human ovaries at different ages, positive circulating ovarian antibodies (AOA) were found in 59% of patients with primitive idiopathic POF (27/46); 20/27 were positive for IgG isotype, 9/27 for IgM and 8/27 for IgA. Specificity of AOA was examined (i) by comparison to different control groups; mean values of the three subclasses of immunoglobins were significantly higher in POF women than in normally cycling fertile young women (n = 23) and fertile young men (n = 17), in untreated Grave's disease (n = 35) or in women with positive antinuclear factor (n = 25); and (ii) by assessing possible cross-reaction; only six out of the 27 positive sera reacted with other tissues (thyroid, pancreas, adrenal), including four clinical polyendocrinopathies. Significance of AOA was explored (i) by comparison with postmenopausal women (n = 40) and older women (n = 15), who did not have enhanced ratios of AOA, thereby excluding a potential role of high FSH values; (ii) by analysing the factors time and surgery; no relation could be found either with the duration of amenorrhoea (6 months to 21 years) or with the history of an ovarian biopsy (12/47) in the absence of any associated pelvic surgery; and (iii) by screening for other immunological factors; familial or personal autoimmune disease (8/46), HLA DR3 (10/42), HLA DR4 (11/42), associated autoantibodies (thyroperoxidase, adrenal, beta islets, parathyroid, DNA, smooth muscles) (12/42). If one positive AOA isotype was present, a second immunological factor was found in 45% of cases. Spontaneous pregnancies during oestrogen therapy occurred in four cases, including three women with positive AOA. Circulating AOA detected by an ELISA may represent a practical and suitable marker for diagnosis of POF. Its use for prognosis and rational treatment needs further evaluation.
We report the cases of four patients with occult, and one patient with overt, ectopic ACTH syndrome. Cushing's syndrome was cured by removal of the ACTH secreting tumour, op'DDD, ketoconazole or bilateral adrenalectomy. Six to 14 months after remission of hypercortisolism, follow-up computed tomography or magnetic resonance imaging of the thorax revealed in all five patients an anterior mediastinal mass 3-5 cm in length that suggested a thymic carcinoma. Exploratory thoracotomy was performed in four cases and allowed the removal of an enlarged, but normal, thymus. Histological examination revealed no tumour but showed benign thymic hyperplasia with negative immunostaining for ACTH. Thymic enlargement spontaneously disappeared 11 months after its demonstration in the patient who did not undergo thoracotomy. The mechanism of this abnormality is thought to be thymic depletion resulting from high plasma cortisol concentrations followed by 'rebound' thymic hyperplasia when cortisol levels fall. Physicians involved in the management of patients with Cushing's syndrome must be aware of this entity in order to avert a diagnostic thoracotomy.
A species of Cellulomonas was isolated from soil by enrichment culture and shown to secrete enzymes capable of degrading mycobacterial cell wall arabinogalactan, both the insoluble peptidoglycan-bound and base-solubilized forms. The major degradation product was purified and characterized as a hexa-arabinofuranoside, [beta-D-Araf-(1-->2)-alpha-Araf-(1-->]2-->3,5-alpha-D-Ara f-(1-->5)-D-Araf. The non-reducing ends of this unit are the sites of mycolic acid attachment and, as they also appear in lipoarabinomannan (LAM), the point of mannose capping in some mycobacteria. Thus, elaboration of the structure of this focal hexasaccharide is critical to our understanding of much of the physiology and pathogenesis of mycobacteria. The extracellular enzymes of Cellulomonas sp. also released the disaccharide, alpha-D-Araf-(1-->5)-D-Araf, from internal linear regions of arabinan and, surprisingly, convert the linear galactan backbone into cyclic oligosaccharides of the structure [-->5-D-Galf-(1-->6)-beta-D-Galf-(1-->]n where n is 2, 3 or 4. Thus, the preparation contains Schardinger-like enzyme activity. This group of enzymes are powerful tools for the dissection of the mycolylarabino-galactan-peptidoglycan (mAGP) complex of mycobacteria towards understanding its role in drug resistance, disease processes and mycobacterial physiology.
Microinjection experiments demonstrated a requirement for cellular ras activity late in G1. In this study, we used two separate methods to identify an additional requirement for cellular ras activity early in the G0/G1 phase of the cell cycle. Quiescent BALB/c cells were injected with anti-ras antibody prior to stimulation with serum. The cells would therefore be inhibited in progression through the cell cycle at the earliest point requiring ras function. Alternatively, cells were inhibited in late G1 as in previous studies by injecting anti-ras several hours after serum addition to quiescent cells. The injected cultures were then treated with chemical cell cycle inhibitors known to function in mid-G1. Cells injected with anti-ras prior to serum stimulation were retained at a point of ras requirement prior to the execution point of the chemical inhibitor, while cells injected 3 to 5 h after serum stimulation were retained at a point of ras requirement downstream of the execution point of the chemical inhibitor. To confirm these results, quiescent BALB/c cells were injected with anti-ras antibody prior to or several hours following serum addition. In this case, however, second injections of oncogenic ras or adenoviral E1A protein were performed to overcome the inhibitory effects of the anti-ras antibody. Cells injected prior to serum addition were clearly inhibited at an early point of Ras requirement since they required 5 or 6 h longer to enter S phase than cells injected with anti-ras antibody after serum addition.
Macrophages have been shown to play a key-role in the development of atherosclerotic lesions. Monocyte attraction and activation in the arterial wall lead to foam cell formation, cholesterol accumulation and secretion of inflammation mediators. Among macrophage secretions, prostacyclin and thromboxane are prostaglandins involved in the regulation of coagulation and vascular permeability. In this study, we have evaluated the effects of human native low-density and high-density lipoproteins on macrophage prostaglandin production (P388D1 mouse cell line). Lipoprotein fractions were purified from venous blood of healthy volunteers by sequential ultracentrifugation. After lipoprotein incubation with cells, supernatants were extracted and prostaglandins quantified by high-performance liquid chromatography. Our technique allows the determination of the main classes of prostaglandins. In the presence of low-density lipoproteins, time-course study showed an increase in total prostaglandin production within 10 min (50 times basal secretion level). This increase was dose-dependent. A steady-state was obtained at 20 mg protein LDL/1. Stimulation of thromboxane B2 and prostacyclin was predominant, with a main effect on the proaggregant thromboxane. Production of the proinflammatory PGF2 alpha and the immunoregulatory PGE2 was lower. In the presence of high-density lipoproteins, P388D1 cells also increased their total prostaglandin secretion at 30 min, in a dose-dependent manner. This increase was directly related to a stimulation of prostacyclin, with no significant effect on thromboxane. Our results demonstrate that normal low-density lipoproteins can stimulate macrophage prostaglandin secretions, with putative deleterious effects on the arterial wall, in particular thrombus formation. On the other hand, high-density lipoproteins, by mainly stimulating prostacyclin, could theoretically have a beneficial influence.
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Foetal macrosomia is arbitrarily defined as an excessive weight for the gestational age, was found to be present in 36 p. 100 of 43 diabetic pregnancies. This finding may indicate incomplete normalization of maternal metabolic control despite the use of new forms of insulin delivery systems, such as insulin pumps. However, in our series the macrosomia was usually moderate and without consequences on the foetal outcome. The levels of insulin, but not those of the insulin-like growth factor (IgF1), were increased in the umbilical cord blood of macrosomic newborns of diabetic mothers. Cardiac septum hypertrophy correlated with maternal glycosylated haemoglobin levels better than with macrosomia. We therefore suggest that in all diabetic pregnancies the cardiac septum thickness should be measured in utero by sonocardiography.
Ovarian responses to stimulation for in vitro fertilization by clomiphene citrate menotropins have been correlated to the hormonal profiles determined during spontaneous cycles. The authors found 80% of high plasmatic luteinizing hormone (LH) and/or androgens levels associated with an inappropriated response: premature LH surge, multifollicular ovarian response, or dissociated cystic response, versus only 11% with appropriated responses. High plasmatic follicle-stimulating hormone existed in 71% of the no response group. Detryptoréline, a luteinizing hormone-releasing hormone agonist associated with menotropins, in a "short procedure" maintained the adequate responses and suppressed premature LH surges. The no response group was moderately improved, as were multifollicular and dissociated cystic response groups. Hormonal profiles could be useful predictive factors of the ovarian response for adaptation on the first procedure of stimulation.
It seems rational to consider that residual insulin secretion is one of the factors which determine the short-term course of inaugural type I diabetes. But what about the mid-term course? We evaluated prospectively the insulin reserve (fasting and post-prandial C peptide) in 52 patients throughout the subsequent development of the disease. The patients (36 men, 16 women, mean age 35 years), who presented with ketonuria and weight loss, received a 10-day course of intensive insulin therapy, after which a remission of insulin dependence was observed in 40 of them (77 per cent). These 40 patients differed from those who had no such remission in that they were heavier and had a better initial insulin secretion. There was no significant difference between the two groups with regards to immunogenetic markers (presence of anti-islet antibodies 28/35 vs 8/12, DR3 and/or DR4 tissue group 27/37 vs 8/10). Following intensive insulin therapy, the C peptide value was consistently increased. At 6, 12 and 18 months the insulin secretion in patients of the remission group remained stable and always higher than that of patients who did not have a remission and whose insulin secretion collapsed at 18 months. Another characteristic of the remission group was that C peptide secretion could be stimulated by meals throughout the follow-up period (post-prandial C peptide at 18 months: 0.63 nmol/l). It is concluded that residual insulin secretion is one of the most effective predictive factors of remission when type I diabetes is first diagnosed and remains stable for the first 18 months of the disease in patients who show a remission.
The prognostic factors and therapeutic approaches in myxoedema coma--a rare but serious medical emergency--were re-evaluated from a retrospective study of 10 cases. The immediate respiratory risk can be prevented by referring these patients immediately to an intensive care unit. The patient's cardiovascular status before and after coma determines the prognosis for life and serves as guideline to treatment. Hormone replacement therapy with initial injection of a loading dose of thyroxine seems to improve the prognosis by ensuring rapid recovery of the principal vital functions.
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The quality of ovarian stimulation for in vitro fertilization with or without an LH-RH analogue was investigated in a randomized trial involving 30 women divided into 3 groups. Group I women were treated with the conventional clomiphene citrate-human menopausal gonadotropin combination without LH-RH analogue. Group II women (long regimen) received a slow-release preparation of triptorelin (DTRp6-LH-RH), an LH-RH analogue, and human menopausal gonadotropin. Group II women (short regimen) were given triptorelin with human menopausal gonadotropin. Inhibition of the endogenous luteinizing hormone using triptorelin improved the results of in vitro fertilization in group II and group III women, but the short regimen was distinctly less compelling and less expensive than the long regimen.
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Hypothalamic amenorrhoea is characterized by deficiency of the pulsatile secretion of the gonadotropin-releasing hormone. In 18 patients with hypogonadotropic hypogonadism a precise topographical diagnosis could be made by pulsatile administration of this hormone using a portable pump, after failure of the simple gonadotropin-releasing hormone test (100 micrograms intravenously). In women wishing to become pregnant, this treatment proved valuable to induce ovulation, being remarkably effective (17 pregnancies in 20 women (85 p. 100) and 2.2 cycles/pregnancy), easy to perform, and safe, as well as less expensive and with less risk of hyperstimulation and multiple pregnancies than the conventional treatment with gonadotropins.
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