Post-traumatic pituitary apoplexy--two case reports

A 60-year-old female and a 66-year-old male presented with post-traumatic pituitary apoplexy associated with clinically asymptomatic pituitary macroadenoma manifesting as severe visual disturbance that had not developed immediately after the head injury. Skull radiography showed a unilateral linear occipital fracture. Magnetic resonance imaging revealed pituitary tumor with dumbbell-shaped suprasellar extension and fresh intratumoral hemorrhage. Transsphenoidal surgery was performed in the first patient, and the visual disturbance subsided. Decompressive craniectomy was performed in the second patient to treat brain contusion and part of the tumor was removed to decompress the optic nerves. The mechanism of post-traumatic pituitary apoplexy may occur as follows. The intrasellar part of the tumor is fixed by the bony structure forming the sella, and the suprasellar part is free to move, so a rotational force acting on the occipital region on one side will create a shearing strain between the intra- and suprasellar part of the tumor, resulting in pituitary apoplexy. Recovery of visual function, no matter how severely impaired, can be expected if an emergency operation is performed to decompress the optic nerves. Transsphenoidal surgery is the most advantageous procedure, as even partial removal of the tumor may be adequate to decompress the optic nerves in the acute stage. Staged transsphenoidal surgery is indicated to achieve total removal later.     

Clinicopathologic and immunogenetic analysis of mucosa-associated lymphoid tissue lymphomas arising in conjunctiva.

PURPOSE: To identify mucosa-associated lymphoid tissue (MALT) type lymphoma in conjunctival infiltrates. METHODS: Clinical, histopathologic, immunophenotypic, and immunogenotypic studies were performed on 14 patients with conjunctival lymphoid infiltrates. Surgical biopsy specimens were subjected to histopathologic, immunohistochemical, and gene rearrangement analysis. RESULTS: Thirteen of the 14 patients (92.9%) met the diagnostic criteria for MALT lymphoma, and the remaining patient showed morphologic features of diffuse, small lymphocytic lymphoma. Genotypic analysis confirmed immunoglobulin heavy chain gene rearrangement in all of the 12 patients on whom the analysis was performed. Two patients with bilateral lesions exhibited identical immunoglobulin rearrangement patterns in each pair of lesions. All patients were alive at the last follow-up (mean: 39.9 months). Nine of the 14 patients were alive without disease, 4 had localized recurrences, and 1 had a residual tumor. CONCLUSIONS: These findings indicate that conjunctival lymphoid infiltrates usually have the features of MALT lymphoma with genotypic B lymphocytic monoclonality and a favorable prognosis.     

Effects of aging on fluorescein leakage in the iris and angle in normal subjects.

PURPOSE: To determine the presence of fluorescein leakage from the iris and angle in normal subjects, and how it is affected by aging. METHODS: The subjects were 92 normal volunteers and patients with senile cataract who ranged in age from 20 to 93 years and were free from any systemic or ocular diseases. Fluorescein iris and angle photography and color iris and angle photography were performed using a goniolens and a photo slit lamp. RESULTS: Radial ciliary body vessels were found in 22 eyes (24%), radial iris vessels or trabecular vessels in 7 eyes (8%), and circular ciliary band vessels were seen in 4 eyes (4%). Goniovessels were found in 8 of 30 eyes (27%) of those under 50 years of age. No significant difference in the incidence of goniovessels was found between those over and under age 50 (P < .01). In the pupillary margin, fluorescein leakage was seen in 1 of 30 eyes (3%) in the age group under 50 years, whereas leakage was found in 30 of 62 eyes (48%) in the age group over 50 years. In the anterior chamber angle, leakage was seen in 4 of 30 eyes (13%) under age 50 years, and in 38 of 62 eyes (61%) over age 50 years (P < .05). CONCLUSIONS: These findings suggested that the incidence of leakage of fluorescein from the pupillary margin and anterior chamber angle tends to increase with age. Thus, when leakage of fluorescein in angle and iris is observed, it is important to consider the physiological changes resulting from aging.     

Analysis of alpha1-adrenoceptor subtypes in rabbit aorta and arteries: regional difference and co-existence.

This study was done to determine the alpha1-adrenoceptor subtypes and to characterize the functional role of alpha1D-adrenoceptors in the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries. In all arteries, selective alpha1D-adrenoceptor antagonist BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspirol(4,5) decane-7,9-dione dihydrochloride) dose dependently shifted the concentration-response curves for norepinephrine to the right. Schild plots of the results obtained from the inhibition by BMY 7378 for norepinephrine yielded a straight line with a slope of unity in thoracic (pA2 6.54+/-0.02) and abdominal (pA2 6.73+/-0.03) aorta. Slopes of Schild plots obtained from the inhibition by BMY 7378 for norepinephrine were significantly different from unity in mesenteric, renal and iliac arteries. Slopes of Schild plots for BMY 7378 were not different from unity in chloroethylclonidine-treated thoracic (pA2 6.49+/-0.14) and abdominal (pA2 6.61+/-0.11) aorta. Slopes of Schild plots for BMY 7378 were significantly different from unity in chloroethylclonidine-treated mesenteric, renal and iliac arteries. On the other hand, in Ca2+-free physiological saline solution (Ca2+-free PSS) slopes obtained from Schild plots for BMY 7378 were not different from unity in thoracic (pA2 6.41+/-0.09) and abdominal (pA2 6.28+/-0.07) aorta and mesenteric (pA2 6.55+/-0.06), renal (pA2 6.24+/-0.10) and iliac (pA2 6.64+/-0.13) arteries. BMY 7378 inhibited [3H]prazosin binding to thoracic (pKi 6.44+/-0.08) and abdominal (pKi 6.59+/-0.02) aorta with low potency, and mesenteric (pKi High 8.66+/-0.28, pKi Low 6.34+/-0.14), renal (pKi High 8.71+/-0.33, pKi Low 6.45+/-0.03) and iliac artery (pKi High 8.60+/-0.24, pKi Low 6.56+/-0.13). These results suggest that alpha1D-adrenoceptors play a significant role for contractile responses in renal and iliac artery, but play virtually no role in thoracic and abdominal aorta and that an alpha1-adrenoceptor subtype, which is pharmacologically distinguishable from the alpha1A-, alpha1B- and alpha1D-adrenoceptor subtype, may co-exist in mesenteric artery.     

Receptor-mediated modulation of voltage-dependent Ca2+ channels via heterotrimeric G-proteins in neurons

The activity of voltage-dependent Ca2+ channels is highly regulated by neurotransmitter receptors coupled to heterotrimeric G-proteins. In the expression studies using cloned Ca2+ channel subunits, it has been clarified that the main mechanism of the inhibition of N-type channel current is mediated directly by G-protein betagamma subunits in a membrane-delimited and voltage-sensitive manner. In addition, recent studies have also clarified that N-type channels are modulated by several G-protein alpha subunits in different ways. Among them, G(alpha o) mediates a voltage-resistant inhibition of N-type current by neurotransmitters. This type of inhibition is more apparent in the case of P/Q-type channels in both native cells and expression systems. Moreover, other G-protein subunits, such as G(alpha q) and G(alpha s), also seem to regulate N-type channels in a membrane-delimited manner. The fine tunings of Ca2+ channel activity by intracellular proteins have physiological and pathological meanings in the regulation of Ca2+ influx into excitable cells by neurotransmitters and pharmacological implications as novel drug targets for controlling Ca2+ influx.     

Effects of a class III antiarrhythmic drug, dofetilide, on the in situ canine heart assessed by the simultaneous monitoring of hemodynamic and electrophysiological parameters

The cardiovascular profile of dofetilide was examined using halothane-anesthetized, closed-chest in vivo canine model (n=6). Dofetilide was administered at the dose of 1, 10 or 100 microg/kg, i.v. over 10 min with a pause of 20 min. After the lowest infusion rate, no significant change was detected in any of the cardiovascular parameters. Infusion of 10 microg/kg dofetilide, which was close to the submaximal clinically effective antiarrhythmic dose, decreased the heart rate and prolonged the ventricular repolarization phase and refractory period. After the highest dose of dofetilide, the cardiac output and left ventricular contraction decreased during sinus rhythm, the latter of which was not changed during the constant heart rate of 150 beats/min, while the dose-related effects were observed on the heart rate, repolarization phase and refractory period. The afterload and preload to the left ventricle and AV nodal as well as intraventricular conductions were hardly affected even at 100 microg/kg, i.v. These results obtained in the in vivo canine model support the previous reports describing that dofetilide possesses a highly selective blocking property for I(Kr). Moreover, the absence of effects on the afterload and preload to the left ventricle and the cardiac conduction makes dofetilide favorable as an antiarrhythmic drug because it is often used for patients with moderate to severe left ventricular dysfunction.     

Discovery of orally active nonpeptide bradykinin B2 receptor antagonists

Orally active nonpeptide bradykinin (BK) B2 receptor antagonists have been discovered by using directed random screening and chemical modification. These compounds displaced [3H]BK binding to B2 receptors in guinea-pig ileum membranes, rat uterus membranes and human lung fibroblasts with nanomolar IC50s. They did not inhibit different specific radio-ligand bindings to other receptor sites including B2 receptors. In isolated guinea-pig ileum preparations, these compounds had no agonistic effect on smooth muscle contraction at 10(-6) M, and caused parallel rightward shifts of the concentration-response curves to BK on contraction with higher p A2 values. They also blocked human B2 receptor-mediated phosphatidylinositol hydrolysis without agonistic effect. In vivo, the oral administrations of these antagonists potently inhibited BK-induced bronchoconstriction in guinea-pigs. They also reduced carrageenin-induced paw edema and caerulein-induced pancreatitis in rats. Moreover, these compounds alleviated kaolin-induced pain in mice by oral administration. These results show that our compounds are potent, selective, and orally active BK B2 receptor antagonists and that they may have therapeutic potential against inflammatory diseases and pain.     

Diurnal variation in neutrophil function

Neutrophil functions, including chemotaxis, reactive oxygen species (ROS)-producing capacity of neutrophils, and serum opsonic activity were investigated in 9 young healthy male volunteers. Venous blood of these volunteers was obtained under standardized conditions at 4-h intervals over a 24-h span. Neutrophil chemotaxis was evaluated by a modified Boyden technique, ROS-producing capacity of neutrophils and serum opsonic activity were measured by a simultaneous multiple measurement system based on luminol-dependent chemiluminescence and indicated by peak height and peak time. ROS-producing capacity of neutrophils and serum opsonic activity were activated in the daytime, and decreased from night to morning. There were negative correlations between the peak time of the luminol-dependent chemiluminescent response, neutrophil number (p<0.01) and segmented neutrophil number (p>0.01). On the other hand, no significant correlations were noted between serum opsonic activity and IgG, IgA, IgM, C3 or C4. In contrast, the peaks of neutrophil chemotaxis were at the wake-up time (6:00a.m.) and in the evening (6:00p.m.). This study indicates that diurnal variation of neutrophil function exists.     

Cytoreductive surgery and sandwich therapy with chemohyperthermic peritoneal perfusion and intra-aortic chemotherapy for peritoneal dissemination in gastric cancer

Cytoreductive resection (RST), chemohyperthermic peritoneal perfusion (CHPP) and/or intra-aortic chemotherapy (IA-chemo) were performed for peritoneal dissemination in gastric cancer. Ninety-six patients with peritoneal dissemination were grouped into tubercular (TB), 40; nodular (ND), 31; diffuse (DF) type, 19; and others, 6, respectively, by the gross findings. Sixty-three patients underwent RST. Fifty-nine patients received CHPP by 10-liter heated saline. Thirty patients underwent intra-aortic catheterization for the IA-chemo. The 1-year and 2-year survival rate (1-ysr and 2-ysr) of the RST(+) group were 47% and 10% significantly greater than the 9% and 0% of the RST(-) group (p<0.001). The 1-ysr and 2-ysr of the CHPP(+) group were 37% and 11% significantly greater than the 27% and 0% of the CHPP(-) group (p=0.04). In the TB type the 1-ysr and 2-ysr of the former was 43% and 8% significantly greater than the 15% and 0% of the latter (p=0.04). But there was no significant difference in survival time between the CHPP(+) and the CHPP(-) group in the ND type (p=0.22) or in the DF type (p=0.42). The 1-ysr and 2-ysr of the IA-chemo(+) group were 49% and 19% significantly greater than the 27% and 2% of the IA-chemo(-) group (p<0.01). In the DF type the 1-ysr and 2-ysr of the former was 50% and 33% significantly greater than the 8% and 0% of the latter (p=0.02). However, there was no significant difference in survival time between the IA-chemo(+) and the IA-chemo(-) group in the TB type (p=0.06) or in the ND type (p=0.50). Moreover, the effect of the combination therapy of CHPP and IA-chemo (the sandwich therapy, SDW) were examined. The 1-ysr and 2-ysr of the SDW(+) group were 49% and 22% significantly greater than the 24% and 0% of the SDW(-) group (p=0.002). The sandwich therapy should be performed in addition to cytoreductive surgery for improvement of prognosis in the patient with intractable peritoneal dissemination.     

Effects of intravenously administered lidocaine on pulmonary vagal afferents and phrenic nerve activity in cats

The ability of lidocaine to suppress activity of single vagal afferent fiber and that of phrenic nerve was studied in 20 cats anesthetized with pentobarbital. Slowly adapting stretch receptors (SAR, n = 16) and rapidly adapting stretch receptors (RAR, n = 7) were identified by their discharge pattern to pulmonary inflation. Intravenous lidocaine (1mg·kg^–1 or 2mg·kg^–1) produced a suppression of SAR activity but not of RAR activity. Suppression of phrenic nerve activity lasted much longer than that of SAR. These findings indicate that iv lidocaine acts more dominantly on CNS than on peripherals. We conclude that iv lidocaine prevents cough and hemodynamic changes caused by airway manipulation mainly through its action on CNS and not on peripherals (peripheral nerves or their receptor).(Aoki M, Harada Y, Namiki A, et al.: Effects of intravenously administered lidocaine of pulmonary vagal afferents and phrenic nerve activity in cats. J Anesth 6: 395–400, 1992)