[Staged operations of acquired lymphangiectasia of the vulva: 10 cases clinical analysis].

Objective: To investigate the characteristics, diagnosis and therapeutic effect of acquired lymphangiectasia of the vulva (ALV). Methods: A retrospective analysis of clinicopathological and follow-up data was conducted on the patients treated in Capital Medical University Affiliated Beijing Shijitan Hospital due to female ALV from July 2009 to July 2023. The patients who completed the staged operations [partial labiectomy and reconstruction + thoracic ductplasty and (or) perineal lymphovenous anastomosis] were included in the study and followed up. The improvement of perineal swelling, blister range, fluid leakage volume and frequency were evaluated through outpatient visits by the symptom rating scale of ALV (hereinafter referred to as the symptom rating scale) before and after surgery. Results: A total of 48 patients were treated due to ALV from July 2009 to July 2023, of which 98% (47/48) were postoperative pelvic malignant tumors and 94% (45/48) had a history of radiotherapy. A total of 10 patients with ALV who completed the staged operations were included in this study. (1) Clinical characteristics and diagnosis: 10 patients had a median age of 60 years old (50, 63 years old ). The median duration from cervical cancer surgery and radiation therapy to vulvar swelling was 1.5 years (0.0, 2.0 years), and the median duration from vulvar swelling to blister formation and leakage was 0.0 years (0.0, 4.8 years). Seven patients (7/10) had a history of recurrent erysipelas; 7 patients (7/10) had the most severe symptom (widespread blisters, persistent fluid leakage, and large amount of fluid leakage); noncontrast magnetic resonance lymphography (NCMRL) showed edema signals in the perineal region of all the patients, and increase of agent in the perineal region was observed in lymphoscintigram (LS). (2) Surgical treatment and postoperative pathological examination: of the 10 ALV patients who completed staged surgical treatment, 6 cases (6/10) were diagnosed with thoracic duct outlet obstruction and underwent thoracic ductplasty and partial labiectomy and reconstruction. Perineal lymphovenous anastomosis and partial labiectomy and reconstruction were performed in 4 cases (4/10) without thoracic duct outlet obstruction. Postoperative routine pathological examination of 10 patients (10/10) showed dermal papilla lymphangiectasia. Immunohistochemical tests were performed on 5 patients, all of which were positive for D2-40 and negative for CD34. (3) Efficacy: 8 patients completed the postoperative follow-up, and the median follow-up time was 31.0 months (17.5, 78.3 months). The perineal swelling and the blister fluid leakage were all significantly improved after the staged operations. All indexes of the symptom rating scale, including the degree of perineal swelling, blister range, fluid leakage volume and frequency, were significantly improved in 8 follow-up patients, and 3 (3/8) of them were cured; the median symptom score decreased significantly from 11.0 before surgery to 3.0 after surgery (P<0.001). The incidence of erysipelas was significantly reduced from 7/10 before surgery to 2/8 after surgery (P=0.035). Conclusions: The main causes of female ALV are pelvic tumor surgery and radiotherapy. The clinical diagnosis is made from relevant medical history, clinical manifestations, LS and magnetic resonance imaging. The diagnosis is confirmed by histopathological findings. Pathological results show lymphangiectasia in the dermal papilla, and immunohistochemical staining show positive for D2-40 and negative for CD34. The effect of staged surgery on ALV is remarkable and even cured, and could effectively reduce the incidence of erysipelas.

[The application of a new type of sterile elastic exsanguination tourniquet in aspiration surgery for upper limb lymphedema].

Objective: To evaluate the effect of a new type of sterile elastic exsanguination tourniquet (SEET) in aspiration surgery for upper limb lymphedema. Methods: The clinical data of 159 patients who underwent aspiration surgery for upper limb lymphedema from January 2017 to June 2022 in the Beijing Shijitan Hospital, Capital Medical University were retrospectively analyzed. Among them, 54 patients were treated with SEET (SEET group), while 105 patients were not treated with SEET (No-SEET group). The propensity score matching method was used, and the surgical indicators and complications were compared between the two groups. The factors affecting intraoperative bleeding volume were analyzed through multiple linear regression analysis. Results: A total of 49 pairs of patients were successfully matched by the propensity score method. The age of patients in the SEET and No-SEET groups was (57.7±8.9) years and (56.8±9.1) years, respectively. Compared with the Non-SEET group, the SEET group had less bleeding volume [(311±164) ml vs (437±173) ml, P<0.001]. The results of multiple linear regression analysis showed that the factors affecting intraoperative bleeding volume included age (ß=-0.142, P=0.041), using the SEET (ß=-0.249, P=0.002), surgical time (ß=0.195, P=0.010) and the amount of fat mixture sucked out (ß=0.464, P<0.001). Conclusions: The clinical application of the SEET in aspiration surgery for upper limb lymphedema is safe, and can significantly reduce the bleeding volume and alleviate blood shortage.

[Lower extremity lymphedema as the initial symptom of malignant disease].

To investigate the diagnosis of malignancy with lower extremity lymphedema as the initial manifestation. We performed a retrospective study of 33 patients with malignant lymphedema treated at the Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University, from May 22, 2007 to December 31, 2018. A total of 33 cases of lower extremity lymphedema caused or aggravated by malignant tumors were found. The age range of 33 patients with malignant lymphedema was 21 to 84 years. Twenty-two patients were male, and 11 patients were female, with a mean age of (57.5±15.0) years. The time from the occurrence of lymphedema to the diagnosis of malignant tumors ranged from a month to 2 years. The proportion of patients with abnormal tumor markers was 88.9% (24/27), the prevalence of anemia among patients with malignant lymphedema was 42.4% (14/33), and the positive rates of ultrasonography, CT, MRI, and radionuclide imaging were 100.0% (17/17), 100.0% (25/25), 100.0% (4/4) and 60.0% (12/20), respectively. Twenty-seven cases with malignant tumors were confirmed by pathological diagnosis. To avoid delays in the diagnosis and therapy of malignant lymphedema, physicians should actively look for signs or symptoms of lymphedema during the follow-up period and promptly manage patients developing problems.

[Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)].

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

[Clinical features of primary isolated chylopericardium: a retrospective review study].

Objective: To examine the clinical characteristics and abnormal reflux branches of primary isolated chylopericardium. Methods: Totally 43 patients with primary isolated chylopericardium at Department of Lymphatic Surgery, Affiliated Beijing Shijitan Hospital,Capital Medical University from June 2007 to January 2018 were recruited in this study. There were 21 males and 22 females, aging (23.0±15.9) years (range: 2 to 57 years). The levels of triglyceride, total cholesterol, total protein and albumin in pericardial effusion and blood were compared by paired-t test, and the characteristics of lymphatic system in direct lymphangiography and postoperative CT were analyzed. Results: Pericardial effusion was mainly milky white and monocytes, and 95.3%(41/43) were positive for Rivalta test. The level of triglyceride in pericardial effusion was significantly higher than that of blood ((9.67±5.11) mmol/L vs. (1.28±0.89) mmol/L, t=10.557, P<0.01), and the levels of total cholesterol ((2.19±0.52) mmol/L vs. (4.12±1.06) mmol/L, t=-3.732, P<0.01), total protein ((61.25±16.17) g/L vs. (68.26±8.30) g/L, t=-2.958, P=0.005) and albumin ((36.63±7.06) g/L vs. (42.32±4.73) g/L, t=-5.747, P<0.01) were significantly lower than that of blood. In the direct lymphangiography, the imaging of iliac and retroperitoneal lymphatics showed dilated or tortuous in 90.7% (39/43), the thoracoabdominal segment of thoracic duct showed dilation in 46.5% (20/43), and cervical thoracic duct imaging showed dilation in 44.2% (19/43) and stenosis in 55.8% (24/43). The image of lipiodol flowing into the vein showed obstruction at the venous angle. There were 60.5%(26/43) of the patients with lipiodol reflux through the bronchomediastinal trunk (type Ⅰ), 11.6%(5/43) with lipiodol diffusion to the pericardium through the abnormal pathway from the thoracic segment of the thoracic duct (type Ⅱ), while no communication pathway between the thoracic duct and the pericardial cavity (type Ⅲ) found in 27.9%(12/43). CT images obtained after the direct lymphangiography showed 34.9%(15/43) had abnormal distribution of lipiodol in pericardium, mediastinal lymph nodes and lung hilar lymph nodes, 46.5%(20/43) in mediastinal lymph nodes and lung hilar lymph nodes, 14.0%(6/43) only mediastinal lymph nodes, 4.6%(2/43) had no lipiodol in the above areas. Conclusions: Pericardial effusion compared with same period blood, has higher triglyceride, lower total cholesterol, total protein and albumin. The obstruction of the cervical segment of the thoracic duct and the formation of abnormal reflux branches would be corelative to primary isolated chylopericardium.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

[Prognostic analysis of definitive radiotherapy for early esophageal carcinoma(T1-2N0M0): a multi-center retrospective study of Jing-Jin-ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group].

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.

[Liposuction combined with lymphatico-venous anastomosis for treatment of secondary lymphedema of the lower limbs: a report of 49 cases].

Objective: To study the clinical effects of liposuction combined with lymphatico-venous anastomosis for treatment of secondary lymphedema of the lower limbs. Methods: A retrospective analysis was performed for 49 patients who had undergone liposuction combined with lymphatico-venous anastomosis to treat secondary lymphedema of the lower limbs at Department of Lymph Surgery, Beijing Shijitan Hospital from November 2013 to February 2015.All patients were female aging from 31 to 70 years with median age of (52±10)years.All patients had history of pelvic surgery.There were 32 cases with cervical carcinoma, 11 cases with endometrial cancer, 1 case with ovarian cancer who accepted radical hysterectomy, 2 cases with benign tumor who accepted resection, 2 cases accepted inguinal lymph node dissection, 1 case with rectal cancer accepted radical resection.There were 30 cases with history of radiation therapy and 23 cases with history of erysipelas recurrent((2.1±3.9)/year). The limb swelling degree in preoperative and postoperative patients was explored using one-way analysis of variance with replicate measures and paired sample t-test. Meanwhile the incidence of lymphogenous infection was used as an evaluation of operation efficacy. Results: The mean lower limb circumference difference at 7 days, 6 months and 12 months was (0.17±1.36)cm, (1.25±1.62)cm and(1.58±1.56)cm, respectively, which was significantly decreased compared with preoperative((4.92±2.16)cm) (t=-5.712, -5.777, -5.765; all P<0.01). The mean lower limb volume difference at 7 days, 6 months and 12 months was (522±799)ml, (726±973)ml and (889±895)ml, respectively, which was significantly decreased compared with preoperative((2 729±1 335) ml)(t=-5.905, -6.093, -5.777; all P<0.01). The incidence of erysipelas was 0.0(0.0, 0.0)/6 months within 6 months after operation and 0.0(0.0, 0.0)/6 months within 6-12 months after operation, which was significantly lower than that before operation(0.0(0.0, 2.0)/year). The feeling of tightness and heaviness of the limb was significantly improved compared with preoperative. Conclusion: Liposuction combined with lymphatico-venous anastomosis is an effective method for the treatment of secondary lymphedema of the lower limbs.

[Clinical analysis of two cases with diffuse pulmonary lymphatic disease].

OBJECTIVE: To analyze the clinical characteristics and diagnosis of 2 cases with diffuse pulmonary lymphatic disease. METHOD: Clinical manifestations of the children were retrospectively analyzed. Two patients were both from Beijing Children Hospital in 2013 and 2014.Diffuse pulmonary lymphatic disease was diagnosed by pathology of pleura in case 1 and by lymphoscintigraphy in case 2. RESULT: The first patient was a male aged 10-year-5-month who presented with a history of pleural effusion for 2 years. Examination revealed chylothorax and pericardial effusion. After pleural decortications and ligation of thoracic duct was performed, he still had recurrent chylothorax. Pathology of pleura revealed lymphangioma. Physical examination showed diminished breath sound and heart sounds. A bronchoscope revealed too much white viscous secretions. Thorax ultrasound revealed lymphangioma in bilateral lower thoracic cavity and post inferior mediastinum. Chest computed tomography showed diffuse thickening of the interlobular septa and bronchovascular bundle in both lungs, many punctate calcification in the lower field. Abdomen ultrasound revealed a small quantity seroperitoneum. Lymphoscintigraphy revealed radioactivity enhancement in bilateral thoracic cavity. The second patient was a female aged 6 years and 9 months, who presented with a history of recurrent cough for 2 years and 9 months. Physical examination showed normal result. Pulmonary function showed mixed ventilation function disturbance. A bronchoscopy showed extensive viscous secretions. Mediastinum, heart and abdomen were normal on ultrasound. Chest computed tomography showed diffuse thickening of the interlobular septa and bronchovascular bundle in both lungs and bilateral pleural thickening. Lymphoscintigraphy revealed diffuse lymphangiectasis in both lungs. Both patients received a diagnosis of diffuse pulmonary lymphatic disease. Case 1 who had died was diagnosed with diffuse pulmonary lymphangiomatosis. Case 2 had no exacerbation after 9 months' treatment with prednisone. CONCLUSION: Diffuse pulmonary lymphatic disease might present with cough and shortness of breath and result in diffuse interstitial disease with thickening of the interlobular septa, refractory chylothorax, multiple lymphangioma in mediastinum, pericardial effusion and seroperitoneum. It could be diagnosed by pleura or lung tissue pathology and lymphoscintigraphy.

Clinical and experimental observation of the length of time of respiratory phase: a preliminary study.

OBJECTIVE: Our goal was to observe the duration of inhaling and exhaling as well as the inhalation to exhalation conversion in patients with lung cancer and experimental dogs. MATERIALS AND METHODS: We recorded lung and tumor respiratory motion with X-ray camera, in five patients with lung cancer as well as in five experimental dogs. We made random observation of breathing cycle inhalation duration, exhalation duration, and inhalation to exhalation conversion within each lung cancer patients and within each of the five animals. RESULTS: Respiratory inhalation duration of each dog and human > exhalation duration > exhale to inhale conversion length > inhalation to exhalation conversion length. During the four breathing cycles, the total respiratory duration differs, and the length of the same breathing phase is inconsistent. CONCLUSIONS: The measurement of early stage breathing duration cannot be representative of breathing duration of the late stage. Radiation treatment planning system based on the pre-computed tomography scanning on the basis of early stage, there will be some radiation dose errors.

QTL detection for eating quality of cooked rice in a population of chromosome segment substitution lines.

The genetic mechanism underlying six palatability properties of cooked rice and three physico-chemical traits was dissected in 66 BC(3)F(2) chromosome segment substitution lines (CSSLs), using a complete linkage map in three successive years. The CSSLs showed transgressive segregation for all traits studied. Significant correlation was detected among most palatability traits. A total of 25 QTLs for the nine traits were identified on nine chromosomes, and many QTLs affecting different quality traits were mapped in the same regions. Six QTLs--qLT-8 for luster, qTD-6 and qTD-8 for tenderness, qIVOE-6 and qIVOE-8 for integrated value of organoleptic evaluation, and qAC-8 for amylose content--were repeatedly detected across the 3 years. Phenotypic values were significantly different between the recurrent parent, cultivar Asominori, and the CSSLs harboring any of the six QTL alleles across the three environments, indicating that these six QTLs were non-environment-specific and could be used for marker-assisted selection in rice quality improvement.

Development of the perforating pathway: an ipsilaterally projecting pathway between the medial septum/diagonal band of Broca and the cingulate cortex that intersects the corpus callosum.

The perforating pathway (PFP) intersects the corpus callosum perpendicularly at the midline in the dorsoventral axis. Therefore axons in either the PFP or the corpus callosum make different axonal guidance decisions in the same anatomical region of the developing cortical midline. The mechanisms underlying these axonal choices are not known. To begin to identify these guidance mechanisms, we characterized the development of these two pathways in detail. The development of the corpus callosum and its pioneering projections has been described elsewhere (Shu and Richards [2001] J. Neurosci. 21:2749--2758; Rash and Richards [2001] J. Comp. Neurol. 434:147--157). Here we examine the development, origins, and projections of axons that make up the PFP. The majority of axons within the PFP originate from neurons in the medial septum and diagonal band of Broca complex. These neurons project in a topographic manner to the cingulate cortex. In contrast to previous reports, we find that a much smaller projection originating from the cingulate cortex also contributes to this pathway. The pioneering projections of the PFP and the corpus callosum arrive at the corticoseptal boundary at around the same developmental stage. These findings show that ipsilaterally projecting PFP axons and contralaterally projecting callosal axons make distinct guidance decisions at the same developmental stage when they reach the corticoseptal boundary.

Release of amines from acidified stores following accumulation by Transport-P.

1. Transport-P is an uptake process for amines in peptidergic neurones of the hypothalamus. It differs from other uptake processes by its anatomical location in post-synaptic neurones, its functional properties and by the structure of its ligands. Transport-P accumulates amines in intracellular vesicles, derives its energy from the electrochemical proton gradient and is linked to vacuolar-type ATPase (V-ATPase). Transport-P is blocked by antidepressants. We have now studied the release of amines following uptake by Transport-P in a cell line of hypothalamic peptidergic neurones. 2. Release of prazosin was not inhibited by the antidepressant desipramine; as Transport-P is blocked by desipramine, this indicated that amines are released by a mechanism which is independent of Transport-P. 3. Release of prazosin was sensitive to temperature and conformed to the Arrhenius equation. Release was minimal in the range 0-25 degrees C but accelerated exponentially at higher temperatures up to 33 degrees C. The activation energy for the release of prazosin is 83.1 kJ x mol(-1), corresponding to a temperature quotient (Q10) value of 3. 4. Release was accelerated by the organic base chloroquine, the ionophore monensin, bafilomycinA1 which inhibits V-ATPase and by increasing extracellular pH. Thus, retention of prazosin requires an intracellular proton gradient which is generated by V-ATPase. 5. Fluorescence microscopy demonstrated that release of BODIPY FL prazosin was temperature dependent and was accelerated by chloroquine and monensin. 6. Thus, following uptake by Transport-P, amines are accumulated in acidified intracellular stores. Their retention in peptidergic neurones requires intracellular acidity. The amines are released by a temperature-dependent process which is resistant to antidepressants.

alpha(1B) adrenergic receptors in gonadotrophin-releasing hormone neurones: relation to Transport-P.

1. Peptidergic neurones accumulate amines via an unusual uptake process, designated Transport-P. [(3)H]-prazosin binds to alpha(1) adrenoceptors on these cells and is displaceable by unlabelled prazosin in concentrations up to 10(-7) M. However, at greater concentrations of prazosin, there is a paradoxical accumulation of [(3)H]-prazosin which we have attributed to Transport-P. Uptake of prazosin via Transport-P is detectable at 10(-10) M prazosin concentration, is linear up to 10(-7) M and at greater concentrations becomes non-linear. In contrast, in noradrenergic neurones, noradrenaline uptake is linear and saturates above 10(-7) M. In noradrenergic neurones and in non-neuronal cells, there is no uptake of prazosin in concentrations up to 10(-6) M, suggesting that Transport-P is a specialised function of peptidergic neurones. 2. Using a mouse peptidergic (gonadotrophin-releasing hormone, GnRH) neuronal cell line which possesses Transport-P, we have studied the interaction of alpha(1) adrenoceptors with Transport-P. Polymerase chain reactions and DNA sequencing of the products demonstrated that only the alpha(1B) sub-type of adrenoceptors is present in GnRH cells. 3. In COS cells transfected with alpha(1b) adrenoceptor cDNA and in DDT(1) MF-2 cells which express native alpha(1B) adrenoceptors, [(3)H]-prazosin was displaced by unlabelled prazosin in a normal equilibrium process, with no prazosin paradox in concentrations up to 10(-6) M. In DDT(1) MF-2 cells, [(3)H]-prazosin was displaced likewise by a series of alpha(1) adrenergic agonists, none of which increased the binding of [(3)H]-prazosin. Hence, the prazosin paradox is not due to some function of alpha(1) adrenoceptors, such as internalization of ligand-receptor complexes. 4. In neurones which possess Transport-P, transfection with alpha(1b) adrenoceptor cDNA resulted in over-expression of alpha(1B) adrenoceptors, but the prazosin paradox was unaltered. Thus, alpha(1) adrenoceptors and Transport-P mediate distinct functions in peptidergic neurones.

Lymphogenous cyst-vein shunt in the management of chylothorax and chylorrhea.

A 36 year-old woman developed marked lymphedema and chylous cysts of the lower abdominal wall, groin, labia, accompanied by chylorrhea. After cyst excision and transplantation of the greater omentum, a left chylothorax occurred. After thoracic duct ligation and left pleurodesis, pleural effusion recurred and worsened. Lymphangioscintigraphy and conventional lymphography suggested that undrained enlarged retroperitoneal lymphatics in the right iliac fossa had disrupted and lymph had leaked into the left chest from the right iliac fossa. Treatment by a lymphatic cyst-vein anastomosis redirected excess chylous lymph into the blood circulation and chylothorax initially remitted. Several years later with recurrence of chylorrhea, the anastomosis was found to be occluded. After a second operative connection between a lymphogenous cyst and the greater saphenous vein, chylorrhea subsided and chylothorax has remitted for more than 4 years.

Castration rapidly decreases hypothalamic gamma-aminobutyric acidergic neuronal activity in both male and female rats.

The postcastration LH response is greater and somewhat more rapid in male than female rats. We have previously demonstrated that hypothalamic gamma-aminobutyric acid (GABA)ergic neuronal activity decreases following gonadectomy in male rats. To investigate whether these same hypothalamic GABA neurons decrease their activity postcastration in female rats, and whether more rapid and or greater postcastration decreases occur in male rats, we determined the timing and magnitude of the postcastration decreases in GABA turnover which are associated with the sexually dimorphic postcastration LH response. Adult male and 4-day cycling female rats were castrated between 0800 and 1000 h (females ovariectomized on diestrus day 1). Serum LH levels increased significantly by 12 h postcastration in both males and females with the magnitude of the increases being 6.2-fold in males and 2.8-fold in females. GABA turnover was determined in 16 microdissected brain structures by the GABA transaminase inhibition method at 0 h (sham-operated controls), 6 h, 12 h and 1, 2, 4 and 6 days postcastration. In male rats, in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis [DBB(ovlt)], the rate of GABA turnover decreased significantly already by 6 h postcastration compared with the 0 h controls, and remained suppressed through 6 days. This rapid down regulation of DBB(ovlt) GABAergic neurons also occurred in female rats, however, the duration of the decrease was not as prolonged as in male rats. Similar changes occurred in the tuberoinfundibular GABAergic (TIGA) neurons projecting to the median eminence in both males and females. Down regulation of these GABAergic neurons precedes or is coincident with increased postcastration LH secretion in both sexes, and the duration of the decreases is consistent with the less robust postcastration LH response in female rats. In addition, the rate of GABA turnover decreased after castration in the interstitial (bed) nucleus of the stria terminalis, ventral aspect (INSTv), the medial preoptic nucleus, dorsomedial aspect (MPNdm) and the ventromedial nucleus, ventrolateral aspect (VMNvl) in male rats, and in the INSTv and VMNvl of female rats, while there was no effect of castration in other hypothalamic regions or control structures. The result in the female VMNvl is consistent with reports that GABA facilitates lordosis behavior in this hypothalamic structure. These findings are consistent with the hypothesis that discrete hypothalamic populations of sex steroid-sensitive GABAergic neurons mediate the postcastration LH responses in both male and female rats, and may underlie other sexually dimorphic adult phenotypes such as sex behavior.

Sex differences in GABA turnover and glutamic acid decarboxylase (GAD(65) and GAD(67)) mRNA in the rat hypothalamus.

GABAergic neurons are estimated to make up more than half of the neuronal population of the hypothalamus and they likely account for some of the structural and functional sexual dimorphisms observed in the mammalian brain. We previously reported sex differences in the rate of GABA turnover in discrete hypothalamic structures of adult rats. In the present study, we extended our search for sex differences in GABA turnover to additional structures, and further determined whether these differences were associated with differences in GAD(65) and or GAD(67) mRNA levels. Utilizing the GABA transaminase inhibition method, we determined GABA turnover in 14 microdissected brain regions. The rate of GABA turnover was about 2-fold greater in male than in diestrous day one (D(1)) female rats in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis [DBB(ovlt)], anteroventral periventricular nucleus (AVPv), median eminence (ME), and dorsomedial portion of the ventromedial nucleus (VMNdm). A sex difference also was noted in the DBB(ovlt) for GAD(65) mRNA determined by microlysate RNase protection assay. Here, GAD(65) levels were almost 2-fold greater in male rats, which suggests that differences in the activity of this GAD enzyme isoform contributes to the difference in turnover in this area. Additionally, in the dorsomedial nucleus (DMN), the GAD(65) mRNA level was significantly higher in female rats, and in the medial amygdaloid nucleus (Am), GAD(67) mRNA was higher in male rats. These data reveal striking sexual dimorphisms in the rate of GABA turnover and in GAD mRNA levels in specific populations of hypothalamic GABAergic neurons. The functional relationships between these GABAergic neurons and sexually dimorphic phenotypes associated with these structures, such as gonadotropin secretion, reproductive behaviors, seizure threshold and others, warrant further investigation.