Determinants of serum leptin levels in Cushing's syndrome

Corticosteroids and insulin increase leptin expression in vivo and in vitro. To investigate whether increased serum cortisol influences serum leptin concentrations in humans, we analyzed fasting serum leptin and insulin levels in 50 patients with Cushing's syndrome [34 female patients: 27 with the pituitary form and 7 with the adrenal form; age, 41.6 +/- 2.7 yr; body mass index (BMI), 29.6 +/- 1.2 kg/m2; 16 male patients all with the pituitary form; age, 39.2 +/- 3.1 yr; BMI, 26.3 +/- 2.3 kg/m2] and in controls matched for BMI, age, and gender. Serum leptin levels were higher in female than in male patients in both the Cushing (P < 0.01) and control (P < 0.001) groups. Disease-specific differences in serum leptin levels were only detected in male (106 vs. 67 pmol/L; Cushing's syndrome vs. control, P < 0.05), not female, patients. Multiple stepwise regression analysis of both patient groups revealed insulin as the best predictor of serum leptin concentrations, accounting for 37% of the variance in serum leptin levels, in contrast to BMI or mean serum cortisol (as measured by sampling in 10-min intervals over 24 h). In the subgroup of patients (n = 9) with pituitary adenoma, serum leptin levels were reduced after tumor resection, with concurrent decreases in serum cortisol, insulin, and BMI. In conclusion, chronic hypercortisolemia in Cushing's syndrome appears not to directly affect serum leptin concentrations, but to have an indirect effect via the associated hyperinsulinemia and/or impaired insulin sensitivity.     

Is adverse pregnancy outcome predictable after blunt abdominal trauma?

OBJECTIVE: The aim of the study was to evaluate the following: (1) pregnancy outcome after blunt abdominal trauma and (2) factors that may predict preterm birth and adverse peripartum outcomes. STUDY DESIGN: All women who had noncatastrophic abdominal trauma and came to the labor and delivery suite July 1994-August 1997 were prospectively evaluated and admitted for continuous uterine and fetal monitoring. A complete blood cell count, coagulation profile, and Kleihauer-Betke stain were performed. Ultrasonographic examination was performed to rule out hematoma. Tocolytic agents were administrated in cases with persistent contractions. Pregnancy outcomes and risk factors were compared between those with preterm birth before 37 weeks' gestation and those who were delivered after 37 weeks' gestation. RESULTS: Delivery information was available for 85 women with blunt abdominal trauma from motor vehicle accident (28), falls (27), and direct assault (30, which included 17 cases of domestic abuse). Four women, 3 of whom were exposed to domestic abuse, were hospitalized twice. Thirteen patients had preterm birth and 72 patients were delivered at term. In all cases the results of Kleihauer-Betke stains, maternal vital signs, blood cell count, coagulation profile, and placental ultrasonographic examinations were normal. The differences between the 2 groups with respect to gestational age at the time of trauma, length of hospital stay, subjective reports of abdominal pain, objective findings of abdominal tenderness, patterns of uterine contractions, interval between trauma and delivery, and Apgar scores were not statistically significant. However, the preterm birth group received magnesium sulfate tocolysis more frequently (31% vs 7%) and had a significantly greater rate of peripartum complications, such as rupture of membranes and abruptio placentae, than the group of patients who delivered at term (46.2% vs 12.5%, P <.05). Women with domestic abuse had increased uterine contractions at the time of abdominal trauma (52.9% vs 19.1%, P =.01) but did not require increased use of tocolysis. Women with domestic abuse had more peripartum complications (41.8% vs 11.8%, P <.01). CONCLUSIONS: Women with noncatastrophic blunt abdominal trauma in pregnancy tend to have favorable neonatal outcomes. Findings or reports of abdominal tenderness and uterine contractions are not predictive of preterm birth. Preterm birth was associated with increased peripartum complications. However, domestic abuse was associated with repeated trauma in the index pregnancy and increased peripartum complications.     

Use of an AC induction motor system for producing finger movements in human subjects

Cushing's disease appears as a functionally heterogeneous disease, but criteria that are able to distinguish between different clinical forms remain elusive. We compared two subgroups of patients with proven Cushing's disease according to the size of the pituitary adenoma, evaluated by computed tomography or magnetic resonance imaging. Our series comprised 11 patients with a microadenoma and 10 with a macroadenoma (median volumes (range): 173 (13-270) and 3022 (500-10312) mm3 respectively; P < 0.0001). The clinical presentation was similar in the two groups, but the time elapsed before diagnosis was longer, and visual impairment was less frequent in the patients with a microadenoma (1.5+/-0.8 years and 0%) than in those with a macroadenoma (0.7+/-0.6 years and 40%; P < 0.05). Morning and evening peripheral concentrations of ACTH were greater in patients with macroadenoma (134+/-78 and 130+/-7 ng/l respectively) than in those with microadenoma (52+/-28 and 56+/-19 ng/l, P < 0.05). Hypokalaemia and lymphopenia were also more pronounced in patients with macroadenoma (3.4+/-0.3 mmol/l and 1273+/-401 lymphocytes/mm3) than in those with microadenoma (3.8+/-0.3 mmol/l and 1852+/-668 lymphocytes/mm3 P < 0.05), although morning and evening plasma cortisol concentrations were similar in both groups. In patients with macroadenoma, there was less relative nycthemeral variation of ACTH concentrations (28+/-24%, compared with 62+/-39% in those with microadenoma; P < 0.05), less suppression of plasma cortisol by high doses of dexamethasone (-30+/-14%, compared with -61+/-25%; P < 0.05), and a reduced concentration ratio of mean basal cortisol to ACTH (7+/-3, compared with 12+/-5; P < 0.05). Plasma IGF-I concentration and the TSH peak response to TRH were significantly lower in patients with macroadenoma than in those with microadenoma (0.4+/-0.2 x 10(3) IU/I and 2.3+/-1.8 mIU/I, compared with 1.8+/-0.6 x 10(3) IU/I and 5.2+/-1.6 mUI/l; P < 0.05). Thus, in comparison with microadenomas, corticotroph macroadenomas are characterized by a greater and more autonomous ACTH secretion, inducing more pronounced biological signs of hypercorticism, and are more often accompanied by visual field defects and impairment of other pituitary hormonal secretions.     

Characterization of cDNA encoding full-length mouse platelet glycoprotein IX

To determine the efficacy and safety of early coronary stenting for unstable angina, we studied 91 consecutive patients with unstable angina. Thirty-one patients underwent stenting 72 h or more after admission, and another 60 patients underwent stenting within 72 h of admission. The clinical and angiographic follow-up had been done for 6 mo. There were no differences between the baseline clinical and angiographic characteristics of both groups. The maximum balloon pressure was higher (14.1 +/- 1.2 vs. 12.6 +/- 0.9, P < 0.01) and the hospital stay was shorter (9.7 +/- 2.7 vs. 18.7 +/- 5.8 d, P < 0.0001) in the early stenting group. These two groups were similar in the clinical success rate (90.0% vs. 93.5%), without any abrupt closure, subacute thrombosis, death, myocardial infarction, or coronary bypass surgery. These findings indicate that early stenting can be useful in patients with unstable angina.     

Cleveland Clinic experience with adrenal Cushing's syndrome

PURPOSE: Cushing's syndrome due to adrenal adenoma or adrenocortical carcinoma is rare. To understand better the clinical and biochemical presentation of this disorder, as well as therapy efficacy and patient survival, we conducted a retrospective review. MATERIALS AND METHODS: Between August 1971 and April 1994, 40 patients presented to our institution with adrenal Cushing's syndrome (27 adenomas and 13 carcinomas). These groups were analyzed with respect to clinical signs and symptoms preoperatively and postoperatively, biochemical analysis, length of postoperative steroid replacement therapy, disease recurrence and patient survival. Followup was obtained by chart review and telephone interviews and averaged 59.6 +/- 66.4 and 47.6 +/- 56.2 months for adenoma and carcinoma patients, respectively. RESULTS: Women predominated in both groups (26 of 27 adenomas, 11 of 13 carcinomas), and tumors affected the left adrenal gland more frequently (19 of 27 adenomas, 9 of 13 carcinomas). Adenoma patients were younger than carcinoma patients (39.6 +/- 14.4 versus 51.5 +/- 16.6 years, p = 0.026) and presented with smaller tumors (3.3 +/- 1.0 versus 8.6 +/- 4.5 cm., p = 0.001). There was a trend toward increased incidence of glucose intolerance among carcinoma patients but no significant differences in clinical signs or symptoms between adenoma and carcinoma patients could be made. Similarly, while there was no significant difference in biochemical evaluation of adenoma versus carcinoma patients, 24-hour urinary free cortisol and serum lactate dehydrogenase levels tended to be higher among carcinoma patients. In addition 17-ketosteroid and dehydroepiandrosterone sulfate levels were more elevated in carcinoma than in adenoma patients, and several adenoma patients actually had subnormal levels. Among adenoma patients mean length of steroid replacement therapy was 16.8 +/- 9.1 months. However, 7 adenoma patients (25.9%) required greater than 24 months of exogenous steroids, and only 1 of these patients was subsequently weaned off steroid replacement. There were no recurrences among adenoma patients, although there was 1 perioperative death due to hypoglycemia. Ten (76.9%) carcinoma patients had recurrences at a mean followup of 33 months. The 3 and 5-year survival rates were 41.5 and 31.2%, respectively. CONCLUSIONS: While presenting signs and symptoms and hormonal analysis may suggest benign or malignant disease, only tumor size and patient age are reliable preoperative indicators of adrenal adenoma versus adrenocortical carcinoma among patients with adrenal Cushing's syndrome. Surgery is curative for adenoma patients, but lifelong steroid replacement may be required. Survival remains poor among carcinoma patients.     

Late complications in remission from Cushing disease. Recurrence of tumor with reinfarction or transformation into a silent adenoma

Two of 4 patients who underwent spontaneous remission from Cushing disease (CD) demonstrated regrowth of the pituitary adenoma 2 and 5 years later. In the first patient, the recurrent tumor also secreted corticotropin, with subsequent relapse of fulminant cushingoid features. However, after 14 more months, it again became infarcted, and the patient underwent complete clinical remission, which has persisted for about 3 years. In the second patient, the regrowth of the tumor occurred silently, as no clinical cushingoid features or rise in cortisol levels were noticed. Because of its size, the tumor was resected and found to have immunoreactivity for corticotropin (silent corticotroph adenoma). About 4 years after the first operation, a second surgical procedure was performed because of massive regrowth of the tumor. Again, there was no concomitant elevation of cortisol levels or endocrinologic symptoms. This time, the tumor did not even stain for corticotropin. While spontaneous remission in CD is rare, recurrence is even rarer. Reremission of CD and the change from a corticotropin-secreting adenoma to a silent one are described herein for the first time (to our knowledge). These cases demonstrate that patients with CD have to receive careful follow-up, even if they undergo remission, and that the long-term outcome of such remission is unpredictable.     

Abnormal progression of a liquid meal through the stomach and small intestine in patients with Chagas' disease

This study describes the abnormal pattern of gastrointestinal progression of a liquid meal in patients with the digestive form of chronic Chagas' disease. This condition is known as a natural model of intramural denervation of the gut. Sixteen patients with clinical and radiographic evidence of esophageal and/or colonic involvement and 18 healthy volunteers were studied. Orocecal transit time after the ingestion of a 10% lactulose solution (180 ml) tagged with 99mtechnetium was measured by a conventional H2 breath technique. Gastric emptying and the arrival of the front of the meal to regions of interest corresponding to proximal and distal areas of the small intestine were assessed by abdominal scintigraphy. Orocecal transit time was significantly greater (P < 0.05) in Chagas' disease patients (N = 13) than in control subjects (N = 18) (mean +/- SD: 100.7 +/- 48.7 min vs 62.9 +/- 18.2 min). Half-time for gastric emptying of liquids in chagasic patients (N = 9) was significantly lower (P < 0.01) than in controls (N = 7) (9.7 +/- 2.7 min vs 26.4 +/- 3.4 min). The time of arrival of the liquid meal to the proximal small intestine was also significantly shorter (P < 0.02) in patients than in controls (5.6 +/- 3.7 vs 11.4 +/- 5.5 min), but there was no difference between the two groups concerning the time the meal first arrived to the distal small intestine (15.0 +/- 11.0 min vs 23.5 +/- 11.4 min, P > 0.05). These results indicate that patients with Chagas' disease have a combination of exceedingly rapid gastric emptying and abnormally delayed transit of liquids through the more distal segments of the small bowel.(ABSTRACT TRUNCATED AT 250 WORDS)     

Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing's disease and no demonstrable pituitary tumor on magnetic resonance imaging

OBJECT: Pituitary surgery has been reported to produce remission of Cushing's disease with preservation of pituitary function in only 60 to 70% of patients. The inability to identify an adenoma accounts for most failed sellar explorations. Most negative surgical explorations occur in patients in whom magnetic resonance (MR) imaging of the pituitary demonstrates normal findings, which happens in at least 35 to 45% of patients with Cushing's disease. METHODS: To examine the usefulness of intraoperative ultrasonography (IOUS) for identifying an adenoma in patients with no demonstrable tumor (negative findings) on pituitary MR imaging. we prospectively assessed the results of IOUS in 68 patients with a negative (59 patients) or equivocal (nine patients) MR image from a consecutive series of 107 patients with Cushing's disease (64%). We compared surgical findings and outcomes in these 68 patients with a group of 68 patients with Cushing's disease and negative findings on MR imaging in whom IOUS was not available. Intraoperative ultrasonography localized a tumor in 47 (69%) of 68 patients with negative findings on MR imaging. Surprisingly, the size of the adenomas that were detected with IOUS compared with the size of those not detected did not differ (6.8+/-3.4 mm compared with 6.1+/-2.8 mm [mean+/-standard deviation], respectively [p=0.51). In four patients, no adenoma was found at surgery or in the pathological specimen ("true negative"). In eight patients, nine abnormalities detected by IOUS that were suspected adenomas were negative on exploration ("false positive"). Thus, IOUS has a sensitivity of 73% and a positive predictive value of 84% for detecting pituitary adenomas in patients with Cushing's disease and negative findings on MR imaging. Compared with the 68 patients who did not undergo IOUS. remission after surgery was improved (61 patients [90%] compared with 57 patients [84%]), the number of tumors found on exploration was increased (61 tumors compared with 51 tumors, p=0.02), and the number of hemihypophysectomies was decreased (five compared with 15; p=0.02) with IOUS. When the groups were compared after excluding patients with prior pituitary surgery, tumors were found in 91% versus 72% (p=0.008), and remission occurred in 95% versus 87% of patients, respectively, in the groups that had or did not have IOUS. CONCLUSIONS: The IOUS is a sensitive imaging modality when used in patients with Cushing's disease in whom findings on pituitary MR imaging are negative. The improved ability to detect and localize these tumors by using IOUS positively affects surgical outcome.     

Increased intraventricular velocities: an unrecognized cause of systolic murmur in adults

OBJECTIVES: The purpose of this study was to determine the frequency, clinical features and echocardiographic characteristics of increased intraventricular velocities (IIVs) in patients referred to the echocardiography laboratory for systolic murmur. BACKGROUND: A subset of patients referred to the echocardiography laboratory for evaluation of a systolic murmur have IIVs in the absence of other recognized causes of systolic murmur. METHODS: We prospectively studied echocardiograms from 108 consecutive patients referred for evaluation of a systolic murmur. Clinical data were obtained from patient examinations and medical records. RESULTS: The sole explanation for systolic murmur was IIVs in 16.7% of referred patients. Compared with those without IIVs, patients with IIVs had a higher ejection fraction (EF) (58.7+/-7.8% vs. 51.1+/-12.5%, p < 0.001), percent fractional shortening (42.3+/-9.7% vs. 31.0+/-11.4%, p < 0.0001), left ventricular (LV) mass index (181+/-70 vs. 152+/-48 g/m2, p=0.046) and prevalence of hypertension (73.3% vs. 51.7%, p=0.043) and a lower prevalence of segmental wall motion abnormalities (2.2% vs. 39.3%, p < 0.001). CONCLUSIONS: Increased intraventricular velocities are a common cause of systolic murmur in this group of patients and should be included in the differential diagnosis of systolic murmurs in adults. The association of IIVs with LV hypertrophy should be a clinical consideration when these murmurs are identified.     

Upregulation of aquaporin 2 water channel expression in pregnant rats

Water retention is characteristic of pregnancy but the mechanism(s) of the altered water metabolism has yet to be elucidated. The collecting duct water channel, aquaporin 2 (AQP2), plays a pivotal role in the renal water regulation, and we hypothesized that AQP2 expression could be modified during pregnancy. Sprague-Dawley female rats were studied on days 7 (P7), 14 (P14), and 20 (P20) of pregnancy, and expression of AQP2 in papillae was examined. Nonpregnant (NP) littermates were used as controls. Plasma osmolalities were significantly lower in pregnant rats by day 7 of gestation (P7 283.8+/-1.82, P14 284.3+/-1.64, P < 0.001, P20 282. 4+/-1.32, P < 0.0001, vs. NP 291.8+/-1.06 mosmol/kgH2O). However, plasma vasopressin concentrations in pregnant rats were not significantly different than in nonpregnant rats (NP 1.03+/-0.14, P7 1.11+/-0.21, P14 1.15+/-0.21, P20 1.36+/-0.24 pg/ml, NS). The mRNA of AQP2 was increased early during pregnancy: AQP2/beta actin: P7 196+/-17.9, P14 200+/-6.8, and P20 208+/-15.5%, P < 0.005 vs. NP (100+/-11.1%). AQP2 protein was also increased during pregnancy: AQP2 protein: P7 269+/-10.0, P14 251+/-12.0, P < 0.0001, and P20 250+/-13.6%, P < 0.001 vs. NP (100+/-12.5%). The effect of V2 vasopressin receptor antagonist, OPC-31260, was then investigated. AQP2 mRNA was suppressed significantly by OPC-31260 administration to P14 rats (AQP2/beta actin: P14 with OPC-31260 39.6+/-1.7%, P < 0.001 vs. P14 with vehicle) and was decreased to the same level of expression as NP rats receiving OPC-31260. Similar findings were found with the analysis of AQP2 protein. The decreased plasma osmolality of P14 rats was not modified by OPC-31260. The results of the study indicate that upregulation of AQP2 contributes to the water retention in pregnancy through a V2 receptor-mediated effect. In addition to vasopressin, other factors may be involved in this upregulation.     

Outcome of differentiated thyroid cancer diagnosed in pregnant women

The clinical features and outcome of thyroid cancer in 61 pregnant women (mean age, 26.0 +/- 5.9 SD yr) and in 528 female, age-matched controls who were not pregnant (mean age, 26.3 +/- 5.9 SD yr) were compared. Median follow-up was 22.4 and 19.5 yr [P = not significant (NS)] in the two groups, respectively. The thyroid nodule was asymptomatic and discovered on routine examination more often in the pregnant women (74%) than in controls (43%, P < 0.001); other clinical and tumor features were similar in the two groups. Most of the pregnant women underwent thyroidectomy after delivery (77%) or during the second trimester of pregnancy (20%). Near-total thyroidectomy was done in 43 (73%) of the pregnant women and 265 (59%) of the controls (P = NS), and nearly the same proportion of both groups (30% and 25%, respectively) were treated with 131I postoperatively. Outcome in the pregnant women and controls, respectively, was: cancer recurrence 9 (15%) and 107 (23%, P = NS); distant recurrences 1 (2%) and 12 (3%, P = NS), and cancer deaths 0 and 6 (1.2%, P = NS). Outcomes were similar when surgery was done during or after pregnancy, despite a longer delay in treatment of the latter (1.1 +/- 1.0 vs. 16.1 +/- 19.7 months, P < 0.001). This study suggests that the prognosis of differentiated thyroid cancer is the same in pregnant women and nonpregnant women of the same age, and that the diagnosis and treatment of thyroid cancer occurring during pregnancy can be delayed until after delivery in most patients.     

Parathyroid hormone after adenectomy for primary hyperparathyroidism. A study of peptide hormone elimination kinetics in humans

The study of the elimination kinetics of peptide hormones in humans is limited, because determining hormone levels in different compartments is difficult. We calculated the elimination kinetics of intact PTH (1-84) after adenoma removal in primary hyperparathyroidism, based on a 2-compartment model. In 12 patients, blood samples were drawn in short intervals preoperatively, during surgery, and up to 4 days postoperatively. Plasma levels of PTH (1-84), calcium (Ca), and inorganic phosphate were determined. PTH (1-84) levels remained constant before surgery and during adenoma preparation; 2.5 min after clamping of the adenoma's blood supply, PTH (1-84) decreased (34.9 +/- 4.8 vs. 23.3 +/- 2.9 pmol/L, mean +/- SEM, P < 0.001) and then reached a minimum of 0.96 +/- 0.06 pmol/L at 5 h. The elimination half-lives for PTH (1-84) were 3.43 +/- 0.1 min and 81.7 +/- 12.7 min. Ionized Ca started to decrease 30 min after adenoma removal (1.58 +/- 0.04 vs. 1.56 +/- 0.04 pmol/L, P < 0.001). This decrease was paralleled by a decrease in total Ca. Inorganic phosphate increased 24 h after adenoma removal. In conclusion, PTH (1-84) elimination after adenectomy is characterized by a rapid initial decrease and a subsequent prolonged period with a lower elimination rate. This elimination pattern may also apply to other human peptide hormones.     

Spontaneous pregnancy toxaemia (ketosis) in sheep and the role of insulin

214 ewes suffering from pregnancy toxaemia (ketosis) were examined. Clinical signs during onset and course of disease and laboratory findings were compared between animals that survived and those which died. In the latter the onset of ketosis was earlier in pregnancy (day 143 +/- 7 vs. day 146 +/- 8) and duration of the disease was shorter (10 +/- 13 vs. 14 +/- 9 days). The animals that died showed more severe clinical signs and higher values of 3-hydroxy-butyrate (4.3 +/- 3.6 vs. 3.5 +/- 2.6 mmol/l) and cortisol (72 +/- 98 vs. 52 +/- 80 mmol/l) as well as lower values of insulin (37 + 12 vs. 3.5 + 2.6 mmol/l) and potassium (4.1 + 1.0 vs. 4.4 + 1.0 mmol/1) at onset of the disease than those which survived (all of differences with P < 0.05). Glucose levels did not differ between groups. Treated animals with glucose plus fructose infusions (n = 56) or with oral application of glucose precursors plus electrolytes (n = 126) had survival rates of 53.6% and 62.7%, respectively. Oral treatment with glucose precursors plus electrolytes and an additional subcutaneous insulin treatment (n = 15) led to an enhanced survival rate of 86.7% (P < 0.05). Low insulin levels in ketotic pregnant sheep and the therapeutic effect of insulin treatment support the hypothesis that insulin plays a causative role in the pathogenesis of ovine ketosis.     

Artificial insemination of Bos indicus heifers: the effects of body weight, condition score, ovarian cyclic status and insemination regimen on pregnancy rate

Effects of body weight, condition score, ovarian cyclic status and insemination regimen on pregnancy rates were investigated in 164 Bos indicus heifers synchronised with norgestomet-oestradiol and pregnant mare serum gonadotrophin (PMSG). Oestrus detection techniques were also compared. Heifers were inseminated at either a fixed time (group 1, n = 83) of 48.0 +/- 0.2 h (mean +/- SEM) after implant removal or at 8.9 +/- 0.5 h after oestrus was detected (group 2, n = 81). Group 2 heifers that were not detected in oestrus by 72 h after implant removal were inseminated at that time. Oestrus was detected for the purpose of insemination using heatmount detectors. Tail-paint and oestrogen treated, chin-ball harnessed steers were used to compare the efficiency of oestrus detection. The probability of ovarian cyclicity increased with increasing body weight and condition score (P < 0.001). A higher proportion of heifers that were acyclic at the commencement of treatment, compared with cyclic heifers, were detected in oestrus at the time of insemination in the fixed-time inseminated group (P < 0.01). Analysis of covariance revealed that intervals from implant removal to oestrus were influenced by ovarian cyclic status (P < 0.01) and insemination group (P < 0.05). A higher pregnancy rate (% +/- SEM) was obtained in acyclic compared with cyclic heifers in the group 1 heifers (50.0 +/- 10 vs 28.1 +/- 6; P = 0.055) but not among the group 2 heifers (45.8 +/- 10 vs 49.1 +/- 7; P = 0.787). The probability of pregnancy was found to be associated negatively with body weight (P = 0.01) while a higher pregnancy rate was obtained in the group 2 compared with group 1 heifers (48.2% vs 34.9%; P = 0.093). The efficiency of oestrus detection was highest using heatmount detectors compared with tail-paint and chin-ball harnessed steers (90.7% vs 37.0% and 23.5%, respectively; P < 0.0001). We conclude that pregnancy rates can be increased in extensive environments when insemination follows oestrus detection using heatmount detectors compared with a fixed-time insemination. The fertility of heifers inseminated at a fixed time is influenced by ovarian cyclic status due to its influence on oestrus-to-insemination intervals.     

Clinical relapses and disease activity on magnetic resonance imaging associated with viral upper respiratory tract infections in multiple sclerosis

Inflammatory lesions of the hypophysis include lymphocytic hypophysitis, pituitary abscess, and granulomatous inflammation, with or without specific infections (i.e., sarcoidosis, mycobacteria). These lesions are known to mimic pituitary neoplasms. We report the clinical and pathologic findings in three patients who underwent transsphenoidal resection for presumed pituitary adenoma. Two were women aged 30 years (one with a 5-month history of headache, the other with a 1-year history of menstrual irregularity) and one was a 12-year-old girl with headache, nausea, and diabetes insipidus. Preoperative endocrinologic studies showed increased prolactin in one patient and normal serum thyroid stimulating hormone and prolactin levels in another. By magnetic resonance imaging (MRI), the first case had a 1.2-cm mass with increased signal on T1 and isointensity on T2, ring enhancement after gadolinium, and lateral deviation of the pituitary stalk. The second patient had a 1.1-cm "cystic" mass seen during magnetic resonance imaging with adjacent bony changes seen during computed tomography. In the third, computed tomography showed a hypodense pituitary mass that enlarged during 1-month observation. At surgery, abnormal soft tissue surrounded liquefied material in the anterior pituitary in all cases. Histologic studies showed fragments of intact normal anterior pituitary with preserved vascular and reticulin network and regions of anterior pituitary infiltrated by foamy histiocytes. Other fragments resembled granulation tissue, and some consisted of acellular debris. Histiocytes were immunoreactive for the macrophage marker CD68 and negative for S-100 and CD1a. Ultrastructurally, the normal adenohypophysis was permeated by lipid-laden macrophages. There were no well-formed granulomas or giant cells, hemosiderin, acid-fast bacilli, or fungi. Serial sections and keratin immunostains failed to identify an epithelial cyst lining or keratin among the debris. We propose the term "xanthomatous hypophysitis" for this lesion.     

Nanomolar quantification and identification of various nitrosothiols by high performance liquid chromatography coupled with flow reactors of metals and Griess reagent

To evaluate the histological findings in patients with chronic hepatitis C and autoimmune features, liver tissue specimens from 60 patients were graded under code for individual features and composite patterns that denoted autoimmune, viral, combined autoimmune and viral, and nondiscriminative changes. Portal, interface, and acinar hepatitis in any combination with plasma cell infiltration connoted an autoimmune pattern that was associated with higher serum levels of gamma-globulin (2.4 +/- 0.2 g/dL vs. 1.7 +/- 0.1 g/dL; P = .0003) and immunoglobulin G (2,211 +/- 227 mg/dL vs. 1,508 +/- 83 mg/dL; P = .001) than patients with other patterns. Patients with the autoimmune pattern also had a greater frequency of cirrhosis (43% vs. 8%; P = .003), higher mean Knodell score (13.2 +/- 0.9 vs. 6.8 +/- 0.9; P < .0001), and a greater occurrence of high-titer smooth muscle antibodies (SMA) (13% vs. 0%; P = .05) than patients with other histological findings. HLA DR3 also occurred more frequently in these individuals than in other patients (48% vs. 15%; P = .01) and normal subjects (43% vs. 16%; P = .01). Patients with nondiscriminative patterns and interface hepatitis had clinical findings similar to those with autoimmune patterns, except for a lower mean serum level of gamma-globulin. We conclude that the composite histological pattern that resembles autoimmune hepatitis is associated with greater immunoreactivity, inflammatory activity, and disease severity than other patterns. Interface hepatitis may be the most important histological finding associated with these clinical manifestations.     

Peripartum cardiomyopathy: a longitudinal echocardiographic study

OBJECTIVE: Our purpose was to determine echocardiographic trends after initial diagnosis of peripartum cardiomyopathy. STUDY DESIGN: Nine women diagnosed with peripartum cardiomyopathy were prospectively recruited for a longitudinal echocardiographic study. Severe myocardial dysfunction was defined as left ventricular end-diastolic dimension > or = 60 mm + fractional shortening < or = 21%, and mild dysfunction was defined as left ventricular end-diastolic dimension < 60 mm + fractional shortening 22% to 24%. Unpaired t tests were used to compare sample means and Fisher's exact test used to compare discrete variables. RESULTS: All women were seen initially for pulmonary edema. Echocardiography showed decreased systolic function in all women. The mean age at diagnosis was 33.0 +/- 6.9 years. All but one woman had a diagnosis of either chronic hypertension (n = 6) or preeclampsia (n = 2). Four women were first seen ante partum and five post partum (range 1 day to 2 months). Repeat echocardiography was performed in all nine women (median 8 months, range 6 weeks to 5 years). There was no correlation between antepartum or postpartum presentation and cardiovascular status on follow-up (p = 0.3). Values for initial left ventricular end-diastolic dimension, severe versus mild dysfunction (68.3 +/- 7.2 mm vs 55.0 +/- 4.2 mm, p = 0.046), follow-up left ventricular end-diastolic dimension, severe versus mild (68.7 +/- 4.1 mm vs 52.0 +/- 5.7 mm, p = 0.002), and follow-up fractional shortening, severe versus mild (14.6% +/- 5.0% vs 28.5% +/- 9.2%, p = 0.02) are significant. Six of the seven women with severe dysfunction had stable disease in follow-up and one is awaiting heart transplant. One of the two women with mild dysfunction had disease resolution and one had stable disease. CONCLUSION: Patients with severe myocardial dysfunction due to peripartum cardiomyopathy are unlikely to regain normal cardiac function on follow-up.     

CD30: expression and function in health and disease

Pituitary adenomas are the most common pituitary disorder affecting pregnancy, and prolactinomas are the most common of the hormone-secreting pituitary adenomas. Hyperprolactinemia must be corrected to allow ovulation and fertility. Bromocriptine has been shown to be safe for use during early gestation. There is less than a 2% risk of microprolactinoma enlargement during pregnancy but a greater than 15% risk of symptomatic enlargement of a macroprolactinoma. Treatment options for patients with macroadenomas include stopping bromocriptine when pregnancy is diagnosed and reinstituting with tumor enlargement, continuous bromocriptine throughout pregnancy, and prepregnancy tumor debulking by surgery. The diagnosis of acromegaly may be difficult to make during pregnancy and relies, in part, on the persistence of the normal pulsatile secretion of growth hormone and loss of this secretory characteristic with a tumor. The growth hormone oversecretion may exacerbate tendencies to gestational diabetes, fluid retention, and hypertension. Treatment for acromegaly and other tumors generally may be deferred until after delivery. There are rare reports of enlargement of clinically nonfunctioning and growth hormone secreting tumors during pregnancy, and surveillance is needed. Tumors may need to be differentiated from lymphocytic hypophysitis. Patients with chronic hypopituitarism usually will need treatment with gonadotropins or pulsatile GnRH to become pregnant and may need increased steroid coverage during labor and delivery. Hypopituitarism developing during pregnancy is usually caused by lymphocytic hypophysitis and usually also will require steroid replacement therapy. Hypopituitarism arising postpartum may be caused by either lymphocytic hypophysitis or Sheehan's syndrome, and the latter may present as an acute or chronic syndrome. Borderline diabetes insipidus may manifest during pregnancy because of increased vasopressin degradation caused by markedly increased levels of placental vasopressinase. Treatment with desmopressin usually is satisfactory. Patients presenting with either anterior or posterior pituitary insufficiency in the peripartum period should always be evaluated for function of the other portion of the pituitary.     

Renal osteodystrophy in diabetic patients

To assess the effects of diabetes mellitus on renal osteodystrophy, we examined the database of 256 patients (45% on hemodialysis and 55% on peritoneal dialysis) who were prospectively studied in three Toronto dialysis centers between October of 1987 and 1989. All patients had serial documentation of their clinical, laboratory and risk parameters of bone disease, and completed a series of investigations that included the deferoxamine test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Twenty-five percent of these patients were diabetic. When compared to non-diabetic patients, they were on dialysis for a shorter duration (2.4 +/- 0.3 vs. 4.7 +/- 0.3 years; P < 0.0002), used calcium carbonate as the only phosphate binder more frequently (40 vs. 25%; P < 0.007), and had lower parathyroid hormone levels (12 +/- 1.4 vs. 24 +/- 2.3 pmol/liter; P < 0.002). High-turnover bone disorders (that is, osteitis fibrosa and mixed disorder) were distinctly uncommon (8 vs. 33%; P < 0.01 by Fisher's exact test), while the mild (19 vs. 9%; P = NS) and the aplastic disorders (with mean stainable bone surface aluminum of 6.5 +/- 0.7%) (46 vs. 31%; P = NS) tended to be more common in diabetic patients. The prevalence of aluminum bone disease was the same in both groups (27%). Diabetic patients ingested a smaller cumulative dose of aluminum gels (3.7 +/- 0.6 vs. 9.3 +/- 1.1 kg; P < 0.005), yet had a higher rate of aluminium accumulation on bone surfaces than non-diabetic patients (1.5 +/- 0.19 vs. 0.96 +/- 0.10% per month on dialysis; P < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)