Ovarian hyperstimulation caused by gonadotroph cell adenoma: a case report and review of the literature.

OBJECTIVE: We present a case of spontaneous ovarian hyperstimulation caused by pituitary gonadotroph macroadenoma, and include a review of the literature. CASE REPORT: A 27-year-old woman presented with irregular menstruation and bilateral multicystic enlargement of the ovaries. Serum estradiol (E(2)) levels were marginally elevated for the follicular phase but within the physiological range. Serum luteinizing hormone (LH) was extremely low, follicle-stimulating hormone (FSH) was normal, and prolactin (PRL) was high. Magnetic resonance imaging disclosed a pituitary macroadenoma. Immunohistochemical examination of the surgically removed adenoma showed intense reactivity for FSH and LH. After the operation, E(2), LH and PRL levels were normalized, the ovaries returned to a normal morphology, and regular menstrual cycles were resumed. CONCLUSION: A review of the literature showed that ovarian hyperstimulation caused by pituitary gonadotroph adenoma is not always accompanied by elevated FSH levels. High PRL and E(2) and low LH were reported in the majority of the cases, but E(2) may stay within the range observed in normal menstrual cycles.     

IgG Anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in guillain-barré syndrome

To investigate the pathophysiological role of anti-GM1 antibody in Gullain-Barre syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patientsrpar;, or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathopsiological mechanisms in IgG anti-GM1)positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers.     

Direct Inhibitory Mechanisms of Halothane on Human Platelet Aggregation

Background: Although halothane directly inhibits platelet aggregation, the mechanisms of this effect are still unknown. The current study aimed to clarify the inhibitory mechanisms of halothane on thrombin-induced human platelet aggregation by measuring (1) platelet-surface glycoprotein Ib expression, (2) the concentration of intracellular free Calcium2+ ([Calcium2+]i) measured simultaneously with aggregation, (3) the concentration of intracellular inositol 1,4,5-triphosphate, and (4) the concentration of intracellular cyclic 3',5'-adenosine monophosphate ([cAMP]i).

Methods: Washed platelet suspensions, obtained from healthy volunteers, were preincubated with halothane (0-2 mM) for 2 min and then exposed to 0.02 units/ml thrombin for 3 min. The glycoprotein Ib bound to fluorescein-labeled antibody was measured by fluorescence flow cytometry. [Calcium2+]i was measured, simultaneously with aggregation, in Fura-2 (Calcium2+ indicator)-loaded platelets by use of a fluorometer. Inositol 1,4,5-triphosphate and [cAMP]i were measured by radioimmunoassay.

Results: Halothane had no effect on glycoprotein Ib expression with or without thrombin. Halothane decreased the thrombin stimulated [Calcium sup 2+]i transient and inhibited platelet aggregation in a dose-dependent manner, both in the presence and in the absence of external Calcium2+. Isoflurane had no apparent effect on either platelet aggregation or [Calcium2+]i in the absence of external Calcium sup 2+. Halothane inhibited the increase in inositol 1,4,5-triphosphate induced by thrombin. Halothane moderately but significantly increased [cAMP]i, but the adenylate cyclase activator forskolin (which has the same inhibitory ability on aggregation as halothane) increased [cAMP]i to a much greater extent than did halothane.     

The kinesin superfamily protein Rab6KIFL is not involved in the pathophysiology of Charcot-Marie-Tooth disease type 4C

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive peripheral neuropathy reported in several Algerian families. The gene locus of this disease has been narrowed to 5q31-33. Recently, a missense mutation in the gene for the kinesin superfamily KIF1B was reported as the cause of Charcot Marie Tooth disease type 2A (CMT2A). We suspected that Rab6KIFL, one of the kinesin superfamily proteins, might be involved in the pathophysiology of CMT4C, because Rab6KIFL gene is located in 5q31. The coding regions of the Rab6KIFL gene of genomic DNA derived from one Algerian family with CMT4C were analyzed by direct sequencing. No mutation in Rab6KIFL gene was found in this family. Further investigation is necessary to identify the causative gene for CMT4C.     

Analysis of wild-type and e antigen-defective hepatitis B viruses during the course of a short-term corticosteroid therapy in chronic hepatitis B

Hepatitis B virus (HBV), with a G-to-A point mutation at nucleotide 83 in the precore region (mutant HBV83), accounts for most cases of hepatitis B e antigen (HBeAg)-defective HBV. However, it is still not clear how mutant HBV83 is associated with HBe seroconversion. Twenty-six HBeAgpositive patients with chronic hepatitis B who received oral prednisolone (30 mg/day) for 3 weeks were studied to clarify the prevalence of mutant HBV83 during the treatment using polymerase chain reaction with a restriction fragment length polymorphism assay. Twelve (46%) patients seroconverted to anti-HBe 1 year after treatment, whereas 14 (54%) did not. The proportion of mutant HBV83 to whole HBV remained unchanged in both groups during an acute exacerbation induced by withdrawal of corticosteroids. Among 12 anti-HBe-0seroconverted patients, five (56%) of nine patients with only wild-type HBV at baseline developed detectable levels of mutant HBV83 while all three patients with a mixed viral population of wild-type HBV and mu tant HBV83 at baseline developed a higher pro portion of mutant HBV83 one year after treat ment. In contrast, these changes were observed in only one (14%) of seven who failed to seroconvert. The results indicate that a flare-up of hepa titis precedes emergence or selection of mutant HBV83, followed by HBe seroconversion in patients with chronic hepatitis B. © 1995 WiIey-Liss, Inc.     

Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis

In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.     

Expression of tumor necrosis factor ligand superfamily costimulatory molecules CD27L, CD30L, OX40L and 4-1BBL in the heart of patients with acute myocarditis and dilated cardiomyopathy.

BACKGROUND: T-cell-mediated myocardial damage is known to be involved in acute myocarditis and dilated cardiomyopathy. Recently, we found that tumor necrosis factor (TNF) ligand superfamily costimulatory molecules, especially 4-1BBL, played an important role in the myocardial damage of murine acute viral myocarditis. METHODS AND RESULTS: To investigate the roles for CD27L, CD30L, OX40L and 4-1BBL, which belong to TNF ligand superfamily, in the development of acute myocarditis and dilated cardiomyopathy, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and dilated cardiomyopathy. We also examined expression of the receptors for these molecules, CD27, CD30, OX40 and 4-1BB, which belong to TNF receptor superfamily, on the infiltrating cells. Strong expression of CD27L, CD30L and 4-1BBL and weak to moderate expression of OX40L was found in the cardiac myocytes of patients with acute myocarditis. Moderate expression of CD27L, CD30L and 4-1BBL and weak expression of OX40L was found on the cardiac myocytes of patients with dilated cardiomyopathy. Most of the infiltrating cells expressed CD27, CD30 and 4-1BB and a part of the infiltrating cells expressed OX40. CONCLUSIONS: Our findings suggest that expression of TNF ligand superfamily costimulatory molecules on cardiac myocytes may play a role in the cell-mediated myocardial damage in patients with acute myocarditis and dilated cardiomyopathy as in murine viral myocarditis.     

Epidemiology of Campylobacter jejuni isolated from patients with Guillain-Barré and Fisher syndromes in Japan

Campylobacter jejuni isolation is the standard for the diagnosis of this type of bacterial infection, but there have been no epidemiological studies of a large number of C. jejuni isolates from patients with Guillain-Barre syndrome (GBS) and Fisher syndrome (FS). For 13 years, stool specimens from GBS/FS patients have been sent from 378 hospitals throughout Japan to the Tokyo Metropolitan Institute of Public Health. A total of 113 strains (11%) were isolated from the stool specimens from 1,049 patients. The isolation rate did not differ by region. The rates were 22% for 449 patients with a history of diarrhea and 2% for the others. An additional 18 isolates were provided by various hospitals. There was no noticeable seasonal distribution in the onset of C. jejuni isolated from patients with GBS/FS. The male/female ratios were 1.7:1 for GBS and 2.2:1 for FS. The patient age range showed a peak in 10- to 30-year-old subjects who had GBS and in 10- to 20-year-old subjects who had FS. The predominance of young adults and male patients who had C. jejuni-associated GBS/FS may be related to the preponderance of young adults and male patients who had C. jejuni enteritis. The median interval from diarrhea onset to neurologic symptom onset was 10 days for GBS/FS. Penner's C. jejuni serotype HS:19 was more frequently present in GBS (67%) than in enteritis (6%) patients. HS:2 was more frequent in FS (41%) than in enteritis (14%) patients. These findings suggest that certain C. jejuni strains specifically trigger GBS and that others specifically trigger FS.     

Pulmonary hypertension due to tumor emboli: A report of three autopsy cases with morphological correlations to radiological findings

Three cases of pulmonary hypertension caused by tumor emboli to the lungs are described. Two of the three cases had a clinical diagnosis of pulmonary thromboembolism until surgical embolectomy, and the other had a diagnosis of primary pulmonary hypertension. Autopsy disclosed chondrosarcoma, choriocarcinoma and gastric cancer as the primary tumors, respectively. Pulmonary vascular obstruction due to tumor embolism leading to pulmonary hypertension is a previously rare clinical entity, and obstructed pulmonary vessels are believed to tend to be small vessels. We compared the autopsy and radiological findings and concluded that pulmonary tumor embolism involved not only the small peripheral arteries but also the segmental and/or lobar arteries.