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Biomedical subjects

R Comtois

Publications and source records attributed to R Comtois.

At least 19 recordsLinked to original sources

Severe mixed connective tissue disease in a woman with pure gonadal dysgenesis: estrogens do not influence disease expression.

Mixed connective tissue disease (MCTD) is more prevalent in women during the child bearing years, suggesting that estrogens may play a role in disease expression. We describe a woman who developed MCTD despite pure gonadal dysgenesis, i.e., a disease associated with permanently very low plasma levels of estrogens. The onset of MCTD and subsequent life threatening disease course over 15 years occurred while she declined exogenous hormonal replacement therapy. Concurrent presence of estrogens is not necessary for onset, persistence, or exacerbation of severe MCTD.

Adolescent↗

Primary sellar haemorrhagic melanoma: case report and review of the literature.

Primary melanoma of the sella turcica is very unusual with only four previous cases reported in the medical literature. This report describes a 47-year-old man whose headaches, endocrine dysfunction and neuro-imaging suggested a haemorrhagic pituitary macroadenoma. The histological examination showed a haemorrhagic melanoma. An extensive search for a primary source proved negative. The patient underwent three neurosurgical interventions and radiotherapy and died two years after presentation. Previous cases of primary melanoma in the pituitary region, as well as various hypotheses for this unusual site of origin are reviewed, followed by a discussion of the particular characteristics of melanin pigments on MRI. This case report illustrates that primary sellar melanoma may present as a haemorrhagic adenoma of the pituitary gland and have an unfavourable outcome despite repeated neurosurgical interventions and radiation therapy.

Cerebral Hemorrhage↗

Variable glycation of serum proteins in patients with diabetes mellitus.

OBJECTIVE: To determine whether there were variations in vivo and in vitro in the glycation process among patients with diabetes mellitus and to assess the characteristics of patients with high and low glycation, if this was observed. PATIENTS: Patients (n = 185) attending a Diabetes Day Care Centre or Notre-Dame Hospital in Montreal participated in the in vivo study. Patients found to have high and low glycation were asked to allow the use of their serum for the in vitro part of the study. INTERVENTION: Capillary blood glucose levels were determined by nursing staff 4 times a day over 7.3 (standard deviation [SD]5.3) consecutive days with commercially available glucose oxydase reagent strips and meters. The ratio of the fructosamine concentration to the protein concentration (the F/P ratio) and the glycated hemoglobin were also determined at the same time as the capillary blood glucose level. Glycation was defined as the mean capillary blood glucose/F/P ratio. Patients with high and low glycation (higher or lower than [SD], of the mean) were compared. For the in vitro study, incorporation of carbon-14 glucose in serum proteins incubated with a 30-mmol/L glucose concentration was studied in some of the patients with low and high glycation. RESULTS: The mean capillary blood glucose/F/P ratio was a mean of 2.30 (SD 0.29) g/mL. Of the 185 subjects 31 had high glycation (1.46 [SD 0.19] g/mL) and 27 had low glycation (2.97 [SD 0.035] g/mL, p < 0.001). There was no significant difference in age, sex, diabetic treatment and glycated hemoglobin levels between the 2 groups. However, patients with low glycation had a greater body mass index (29.4 [SD 5.7] kg/m2 v. 26.4 [SD 4.3] kg/m2, p < 0.05). In vitro, incorporation of 14C glucose in serum proteins incubated with a 30mmol/L glucose concentration was higher in the 9 patients with high glycation than in that of the 7 with low glycation (0.031% [SD 0.03%] per gram of proteins v. 0.028% [SD 0.03%] per gram of proteins, p < 0.02). CONCLUSIONS: Glycation may vary among patients with diabetes mellitus who have similar capillary blood glucose concentrations. Glycation appears to be lower in patients with a greater body mass index. Furthermore, alternation in the glycation process itself may explain, in addition to the mean blood glucose level, the difference in fructosamine levels.

Adult↗

High prolactin levels may be missed by immunoradiometric assay in patients with macroprolactinomas.

OBJECTIVE: Large amounts of antigen may produce falsely low values in immunoradiometric assays due to the so-called high dose, hook effect. The study was designed to identify the clinical and biochemical features of patients with pituitary macroadenomas in whom a high dose PRL hook effect was documented. DESIGN: The clinical and biochemical features of four patients with the high dose PRL hook effect were compared with those of 54 patients with pituitary non-functioning adenomas and 11 with macroprolactinomas who underwent transsphenoidal microsurgery between 1989 and 1994. MEASUREMENTS: The presence of the high dose PRL hook effect was confirmed by an increase in the initial PRL concentration when the immunoradiometric assay was processed after dilutions of the serum. This phenomenon was observed in 5.8% (4/69) of patients with pituitary macroadenomas. Undiluted median (range) PRL levels were 9140 (1530-83850), 1530 (162-3210) and 2110 mU/l (1470-45,000) in patients with macroprolactinoma, non-functioning macroadenoma and the hook effect, respectively. In patients with the hook effect, the median PRL levels increased to 384,720 (317,520-950,000) mU/l when the assay was performed after serum dilution. The proportion of males was 9.9% (1/11) in the macroprolactinoma group, 46.3% (25/54) in the non-functioning macroadenoma group and 100% (4/4) in patients with the hook effect. Patients with prolactinoma and non-functioning adenoma had mean tumour sizes of 20 +/- 9 and 27 +/- 11 mm (SD), respectively, while in the hook effect group it was 51 +/- 10 mm. CONCLUSION: This study suggests that the high dose PRL hook effect is observed particularly in patients with very large tumours. The immunoradiometric PRL assay must be performed with serum dilution in order to overcome the high dose PRL hook effect in all new patients with pituitary macroadenomas who may have a prolactinoma.

Adenoma↗

Surgical outcome after repeated transsphenoidal surgery in acromegaly.

Transsphenoidal selective adenomectomy is the most efficient primary treatment for acromegaly. However, management of persistent or recurrent disease remains controversial. The objective of the present study was to evaluate the early and long-term efficacy and safety of a second transsphenoidal surgery performed in those cases. The results of a retrospective study of 16 patients undergoing reoperation by the senior author (J.H.) between 1970 and 1991 are reported. Reoperation was performed for persistent or progressive acromegaly in 11 patients, visual impairment in four, and disease recurrence in one. Normalization of growth hormone (GH) was defined as a basal GH level of less than 5 micrograms/L and suppression to less than 2 micrograms/L during the oral glucose tolerance test. Long-term follow-up data were available in 15 patients. The second transsphenoidal surgery induced a greater than 50% decrease of GH level in 11 patients. Three (19%) of 16 patients were cured according to the authors' criteria and remained so after 2, 7, and 20 years. Two more patients had a postoperative basal GH level of less than 5 micrograms/L but incomplete suppression during the oral glucose tolerance test. Thus, a total of five patients (31%) achieved a basal GH of less than 5 micrograms/L. One other patient who had no initial improvement after the second transphenoidal surgery had spontaneous normalization of his GH level after 13 years. The following complications of the second surgery occurred in three patients: one subarachnoid hemorrhage, two new visual field defects, one cranial nerve palsy, and one meningitis. Moreover, 10 patients (62.5%) developed one or more new pituitary hormone deficiencies. In conclusion, reoperation for persistent or recurrent acromegaly has low success and high complication rates. According to the authors' experience, this procedure should be reserved for patients unresponsive to other forms of therapy or with progressive visual impairment despite medical therapy.

Acromegaly↗

Outcome of hypothyroidism caused by Hashimoto's thyroiditis.

BACKGROUND: Hypothyroidism is a common condition that is frequently irreversible and requires lifelong thyroid replacement therapy. OBJECTIVE: To assess the incidence and factors that can predict reversibility of hypothyroidism caused by Hashimoto's thyroiditis. METHODS: We studied 79 patients in whom Hashimoto's thyroiditis was diagnosed according to suggestive cytologic features and/or the presence of thyroid antibodies (antimicrosomal antibody titer, > or = 1:1600; antiglobulin antibody titer, > or = 1:400). All patients were initially hypothyroid (serum total thyroxine level, 83.5 +/- 28.6 nmol/L [6 +/- 2 micrograms/dL]; thyrotropin level, 24.7 +/- 28.3 mU/L). Levothyroxine sodium was then administered for 1 year to normalize results of thyroid blood tests. Thereafter, the treatment was stopped for 3 weeks and serum thyrotropin and total thyroxine concentrations were determined. RESULTS: After withdrawal of levothyroxine treatment, thyroid blood tests showed that the degree of hypothyroidism worsened in 20 patients, remained unchanged in 40, and improved in 19. Nine patients (11.4%) did show normalization of the thyroid blood tests. Before treatment, the presence of the following in a patient--of a goiter that is 35 g or larger, thyrotropin levels greater than 10 mU/L, and an anamnestic familial incidence of thyroid disease--was clearly associated with an increased incidence of recovery of normal thyroid function (relative risk, 5.4; 95% confidence interval, 2.8 to 10.7; P < .0002). CONCLUSIONS: Our results confirm that hypothyroidism caused by Hashimoto's thyroiditis is not always permanent. The presence of a larger goiter and high thyrotropin levels at the time of diagnosis, associated with a familial incidence of thyroid disease, may be related to an increased incidence of hypothyroidism remission.

Adolescent↗

Coexistence of hypothyroidism and myocardial infarction.

OBJECTIVE: To assess the coexistence of overt hypothyroidism and acute myocardial infarction (MI) in respect of clinical and biological manifestations and outcome. DESIGN: Retrospective study of patients with coincident untreated or uncontrolled hypothyroidism presenting to Notre-Dame Hospital with acute MI. Each patient's MI was matched with two controls for date of admission (within three years) of MI, age, sex, diabetes mellitus and number of previous MIs. SETTING: All patients were admitted to Notre-Dame Hospital, which is a secondary and tertiary care institution. PATIENTS: From 1975 to 1990, 5691 patients were seen at the authors' institution with acute MI, of whom 17 had simultaneously an untreated or uncontrolled hypothyroidism. Hypothyroidism was defined as thyroid-stimulating hormone levels greater than 40 mU/L associated with low or normal levels of serum thyroxine. RESULTS: Chest pain was documented in each case. Electrocardiogram location of the MI was inferior in 10 (59%) patients and in 14 (41%) controls, anterior in seven (41%) patients and in 20 (59%) controls. There was a trend towards higher creatine kinase peak levels in patients with hypothyroidism (1409 +/- 1145 U/L versus 943 +/- 788 U/L). The Killip index was similar in the two groups (1.8 +/- 1 versus 1.8 +/- 1), as was the incidence of arrhythmias (seven of 17 versus 11 of 32). There was no significant difference in mortality between the two groups (18% [three of 17] versus 12% [four of 34]). However, the incidence of residual ischemia was greater in patients with hypothyroidism (12 of 17 versus 10 of 34, P < 0.008). CONCLUSIONS: Hypothyroidism is not associated with an unfavourable effect on the clinical course of acute MI. However, patients with hypothyroidism seem to have an increased incidence of residual ischemia.

Age Factors↗

High prolactin levels in patients with Cushing's disease without pathological evidence of pituitary adenoma.

OBJECTIVE: This study was designed to compare the clinical and biochemical features of patients with Cushing's disease without pathological evidence of pituitary adenoma (n = 11) to those in whom a pituitary ACTH adenoma was documented (n = 11). DESIGN: The clinical and biochemical features of 11 patients with Cushing's disease without pathological evidence of pituitary adenomas were compared to 11 subjects with ACTH-secreting adenomas. The patients underwent transsphenoidal microsurgery between 1979 and 1989. During surgery, when an adenoma was not visualized, a partial hypophysectomy of the central mucoid wedge was performed. MEASUREMENTS: Cushing's disease was established by the clinical features of hypercortisolism and the high levels of 24-hour free urinary cortisol with no suppression in response to low, but with suppression in response to high, doses of dexamethasone. Basal and post TRH-GnRH plasma prolactin, FSH and LH levels were assessed in each patient before transsphenoidal microsurgery. RESULTS: Similar results were observed in patients with and without ACTH-secreting adenomas regarding cure rate, and free urinary cortisol levels both basal and after 2 days of dexamethasone, 8 mg daily. After surgery, plasma cortisol levels in cured patients were lower in subjects with ACTH-secreting adenomas than in those without pituitary tumours (P < 0.05). Areas under the curve of PRL (P < 0.002) and LH (P < 0.04) were significantly higher in patients without pituitary adenoma after TRH-GnRH administration. Compared to controls, the peak prolactin level after TRH-GnRH administration was higher in patients without pituitary adenoma (P < 0.005) and lower in those with ACTH adenoma (P < 0.005). Furthermore, a peak prolactin level equal to or greater than 1410 mU/l during the TRH-GnRH test was found in 11/11 patients without ACTH adenoma and 3/11 patients in the other group (P < 0.001), while the CT-scan findings were suggestive of pituitary adenoma in six patients of each group. CONCLUSION: This study suggests that patients with Cushing's disease without pituitary adenomas can be distinguished from those with ACTH-secreting adenomas by their high prolactin levels after TRH-GnRH administration.

Adenoma↗

Assessment of the efficacy of iodine-131 for thyroid ablation.

It is customary to ablate residual tissue after near-total thyroidectomy for thyroid carcinoma by administering 131I. A recent trend has been to use lower 131I doses. This study was designed to assess the efficacy of thyroid ablation by 1110 MBq of 131I (30 mCi) in patients who had near-total thyroidectomy for papillary, mixed or follicular thyroid carcinoma. Four months after surgery, a whole-body scan was done using 185 MBq (5 mCi) of 131I after withdrawal of L-thyroxine for 5-6 wk. Residual thyroid area was then measured by planimetry of the thyroid scan. Patients received ablation therapy within 5 days after scanning and one or more subsequent scans were performed 6 mo later. Forty-four patients were treated to ablate residual functional thyroid tissue. Of these, 12 (27%) had successful ablation. Total body areas (1.63 +/- 0.16 versus 1.83 +/- 0.30, p < 0.03) and residual thyroid tissue (1.4 +/- 1.4 versus 2.0 +/- 1.2 cm2, p < 0.05) were less in patients with total thyroid ablation while there was a trend for a smaller incidence of associated goiter in those patients (1/12 versus 13/32, p < 0.07). Nine of the 17 (53%) patients with a total body area less than 1.9 m2 and/or with a residual thyroid tissue less than 2.1 cm2 and/or without associated previous associated diffuse or multinodular goiter had a total thyroid ablation, while 3 of the 27 (11%) patients who did not have these characteristics had a successful therapy (p < 0.005). Our data suggest that 1110 MBq (30 mCi) of 131I can achieve total ablation of residual thyroid tissue after near-total thyroidectomy particularly in patients with lower total body area and smaller residual thyroid tissue without associated previous diffuse or multinodular goiter.

Adenocarcinoma, Follicular↗

Comparison of obese and non-obese patients with gestational diabetes.

The aim of this study was to assess the effect of obesity on the outcome of gestational diabetes (GD). The age of the subject (31 +/- 5 years) and duration of pregnancy (29 +/- 5 weeks) were similar at the time of diagnosis for the 19 obese (34 +/- 6 kg/m2) and 19 non-obese (23.0 +/- 2.1 kg/m2) subjects. Before treatment, the area under the curve of the glucose tolerance test and the mean capillary blood glucose levels were similar in both groups; however, the baseline blood glucose levels of the obese patients (6.0 +/- 0.8 mmol/l) were higher than those of the non-obese patients (5.3 +/- 0.8 mmol/l; P < 0.01). During pregnancy, the total weight gain of the obese patients was less (10.6 +/- 5.0 vs. 15.2 +/- 4.7 kg, P < 0.006). Fifteen of the obese patients required treatment with insulin, while only six of the non-obese women required insulin (P < 0.005). During insulin therapy, the mean capillary blood glucose, glycosylated haemoglobin and fructosamine levels were similar in both groups. In conclusion, our data suggest that GD in obese patients is characterized by lower weight gain and higher baseline glucose with the result that insulin therapy is more frequently instituted.

Adult↗

Clinical usefulness of high-pressure liquid chromatographic determination of serum pentamidine in AIDS patients.

We have developed a reproducible HPLC method to determine serum pentamidine, which demonstrates good chromatographic performance, and is sensitive enough to measure therapeutic doses. Pentamidine is first extracted from serum by passage through a C-18 extraction cartridge. Potential interfering substances are then removed by washing with 100% methanol. Pentamidine is eluted from the extraction cartridge with 1-heptanesulfonic acid. The extract is chromatographed on a highly deactivated column for basic compounds in the presence of minimal concentrations of 1-heptanesulfonic acid as the pairing agent. Detection is by fluorescence. The method can determine serum pentamidine levels in the range of 15-600 ng/mL free of interference from other drugs. In monitoring pentamidine levels in AIDS patients with Pneumocystis carinii, we found that trough serum levels over 100 ng/mL were associated with toxicity (hypoglycemia or azotemia) in 100% of patients. With levels under 100 ng/mL, signs of toxicity were observed in only 29% of the patients. We conclude that dose adjustment based on serum levels reduces the incidence of toxicity and enhances pentamidine therapy.

Acquired Immunodeficiency Syndrome↗

High pentamidine levels associated with hypoglycemia and azotemia in a patient with Pneumocystis carinii pneumonia.

We report on a patient who presented with a Pneumocystis carinii pneumonia. Intravenous pentamidine (4 mg/kg/day) was given for 14 days without the occurrence of adverse effects. During this treatment, the mean (+/- SD) serum pentamidine trough concentration was 94 +/- 16 ng/ml. Three days later, the patient was admitted because of fever, and pentamidine (4 mg/kg/day) was again started. Fasting hypoglycemia and azotemia then occurred; the mean serum trough pentamidine level was 190 +/- 10 ng/ml during this week of treatment. We conclude that the occurrence of hypoglycemia and azotemia during pentamidine therapy may not be idiosyncrasic, but seemed associated in our patient with high levels of serum pentamidine.

AIDS-Related Opportunistic Infections↗

Higher pentamidine levels in AIDS patients with hypoglycemia and azotemia during treatment of Pneumocystis carinii pneumonia.

Trimethoprim-sulfamethoxazole (TMP-SMZ) and pentamidine are both licensed for the treatment of Pneumocystis carinii pneumonia (PCP). However, their use is associated with various adverse side effects. In this prospective study, 26 AIDS patients with 32 episodes of PCP were treated with pentamidine (4 mg/kg/d). Each patient was treated for 12 to 21 days, depending on the rapidity of onset of the clinical response. During the 32 PCP episodes, hypoglycemia occurred in 16 instances, azotemia in 12, liver toxicity in 10, and leukopenia in 8. The occurrence of thrombopenia, leukopenia, and liver toxicity was not related to age, pentamidine levels, or other complications. However, patients who had hypoglycemia during pentamidine treatment had higher serum pentamidine levels than patients who did not have hypoglycemia (107 +/- 40 versus 70 +/- 26 ng/ml, p less than 0.004). In addition, we observed that patients with azotemia showed higher pentamidine levels during treatment (120 +/- 35 versus 64 +/- 22 ng/ml, p less than 0.001). In fact, 100% (11/11) of patients with serum pentamidine concentration greater than 100 ng/ml had fasting hypoglycemia and/or azotemia, while 33% (7/21) of those with pentamidine levels less than 100 ng/ml had these side effects (p less than 0.001). The relative risk of these complications with pentamidine levels greater than 100 ng/ml was 3 (95% confidence interval, 1.6 to 5.5). Fine-tuning the dose of pentamidine may eventually prove useful to avoid toxicity and optimize therapy.

Acquired Immunodeficiency Syndrome↗

Increase in T3 levels during hypocorticism in patients with chronic secondary adrenocortical insufficiency.

The clinical and biochemical manifestations of secondary adrenocortical insufficiency are not well defined in the medical literature. This study was designed to determine the clinical and laboratory features suggesting the diagnosis of adrenal insufficiency in 15 chronic ACTH deficiency patients during low and normal cortisol states. Except for fatigue and weakness, the characteristic clinical manifestations of primary adrenal insufficiency occurred rarely. ACTH deficiency did not significantly modify blood glucose, serum calcium, sodium, potassium and differential white blood cell count. However, serum T4 was lower (65 +/- 19 vs 95 +/- 21 nmol/l, p less than 0.001) during cortisol deficiency, while T3 was higher (2.4 +/- 0.67 vs 2.0 +/- 0.60 nmol/l, p less than 0.001). Furthermore, rT3 decreased significantly during hypocorticism (0.27 +/- 0.07 vs 0.18 +/- 0.07 nmol/l, p less than 0.001). The T4/T3 ratio was significantly lower than the normal in 15 out of the 17 episodes of ACTH deficiency (29 +/- 12.5 vs 57 +/- 9.4, p less than 0.0001). We conclude that the increase in T3 and decrease in T4 levels are associated with chronic secondary adrenocortical insufficiency. This laboratory feature could be due, at least in part, to the increased peripheral conversion of T4 to T3 during cortisol deficiency.

Adrenal Cortex Diseases↗