bluuebunny/crossref_metadata_2025 huggingface dataset:
URGENSI PENDIDIKAN MULTIKULTURAL DALAM MEMBANGUN INTEGRASI NASIONAL
Authors: Muhammad Rifqi Zamzami  , M. Rofiqul Majid
Published: February 2024

Era globalisasi ini Indonesia dihadapkan dengan berbagai jenis tantangan dalam ini pendidikan multicultural dapat di persepsikan sebagai jalan untuj menuju keinginan bangsa. Tujuan pendidikan multikultural adalah untuk secara langsung menanamkan humanisme, pluralisme dan demokrasi pada generasi muda.Penelitian ini menggunakan metode kajian pustaka (Library Research). Dalam pengumpulan data peneliti menggunakan teknik dokumentasi dengan mempelajari dan mengkaji informasi dari sumber-sumber data, baik sumber data primer maupun sekunderuntuk mewujudkan kerukunan yang abadi di Indonesia, diperlukan upaya yang cermat dan tepat untuk meningkatkan kesadaran masyarakat. Guru merupakan komponen terpeniting dalam sebuah pendidikan Bangsa Indonesia membutuhkan pendidikan multikultural untuk mengurangi jumlah konflik horizontal yang terjadi antar masyarakat karena perbedaan budaya, suku, adat, atau agama. Pendidikan multikultural menekankan pada pendidikan yang menghargai perbedaan, karena perbedaan tersebut merupakan aturan yang wajar yang harus dilawan, bukan sebagai sumber perpecahan manusia, karena perbedaan adalah rahmat Allah SWT.
IMPLEMENTASI KURIKULUM MERDEKA (STUDI KASUS DI SMP PONPES MANBAUL HIKMAH KALIWUNGU)
Authors: Suciptono
Published: February 2024

The 2013 curriculum is the curriculum that has been implemented so far as the national curriculum since the 2013/2014 school year. The emergency curriculum is a learning loss recovery curriculum that occurs in special conditions and has the principle of diversification which refers to the 2013 curriculum with core competencies and basic competencies but is simplified and implemented during  the Covid-19 learning  period. Meanwhile, the independent curriculum is a curriculum that was formerly known as a prototype curriculum which was later developed as a more flexible curriculum framework, while also focusing on essential material and character development and student competencies. The program revealed by the Minister of Education and Culture Nadiem Anwar Makarim has attracted a lot of attention from education observers. Manbaul Hikmah Kaliwungu Middle School is one of the schools that pioneered implementing the independent curriculum. This school has implemented an independent curriculum for less than one year. The application of the Independent Curriculum also includes learning Islamic religious education. This school has operated quite well in implementing the independent curriculum in learning, even though there are some obstacles that occur in it. However, the implementation of the independent curriculum in Islamic religious education subjects can still run well. In the implementation stage of the independent curriculum, the principal thought of the SMP Manbaul Hikmah Kaliwungu principal is the integration of the typical Manbaul Hikmah curriculum, namely the Kaffah curriculum. So that as a driving school that previously implemented a prototype curriculum, it changed to implementing an independent curriculum. Even so, this change did not dampen the spirit of the school principal to be optimistic that SMP Manbaul Hikmah Kaliwungu would be able to implement it.
GAGASAN PENDIDIKAN INTEGRASI MADRASAH MODERNIS PERSPEKTIF K.H. AHMAD DAHLAN
Authors: Ilham A'abadia Eko Arif , Ahmad Adrian Fahmi Al Huda
Published: February 2024

Pendidikan di Indonesia mengalami gejolak dan masa transisi yang panjang. Dikotomi keilmuan dalam pendidikan umat Islam dunia adalah salah satu problem yang juga melanda pendidikan di Indonesia prakemerdekaan. Salah satu faktornya ada campur tangan Belanda, oleh Van Devender pada tahun 1899 yang mencetuskan politik etis melalui pemberian pendidikan kepada penduduk bumi putera. Dinamika sosio-keagamaan masa kolonial Belanda dengan upaya hutang budi dalam bentuk politik etis di satu sisi mengakibatkan kenyataan dikotomis keilmuan sekaligus polarisasi umat Islam. Dan secara historis, politik etis kolonialisme mampu melesukan pendidikan Islam dan membentangkan dikotomis keilmuan. Dalam konteks inilah, penelitian ini dilakukan untuk mencermati upaya akomodatif K.H. Ahmad Dahlan dalam proses pembaharuan madrasah sebagai basis utama pendidikan agama Islam. Penelitian ini menggunakan pendekatan kualitatif dengan metode studi pustaka dan analisis isi. Hasil dari penelitian ini mengemukakan temuan bahwa gagasan madrasah modernis dalam bentuk integrasi keilmuan oleh K.H. Ahmad Dahlan mampu mendamaikan dikotomis. Konsep kurikulum integralistik tersebut meliputi: Al-Quran, Hadis, Akhlak, dan Ilmu-ilmu Sosial.
Optogenetic stimulation of the locus coeruleus enhances appetitive extinction in rats
Authors: Lui Simon , Brink Ashleigh K , Corbit Laura H
Published: February 2024

Extinction is a specific example of learning where a previously reinforced stimulus or response is no longer reinforced, and the previously learned behaviour is no longer necessary and must be modified. Current theories suggest extinction is not the erasure of the original learning but involves new learning that acts to suppress the original behaviour. Evidence for this can be found when the original behaviour recovers following the passage of time (spontaneous recovery) or reintroduction of the reinforcement (i.e. reinstatement). Recent studies have shown that pharmacological manipulation of noradrenaline (NA) or its receptors can influence appetitive extinction; however, the role and source of endogenous NA in these effects are unknown. Here, we examined the role of the locus coeruleus (LC) in appetitive extinction. Specifically, we tested whether optogenetic stimulation of LC neurons during extinction of a food-seeking behaviour would enhance extinction evidenced by reduced spontaneous recovery in future tests. LC stimulation during extinction trials did not change the rate of extinction but did serve to reduce subsequent spontaneous recovery, suggesting that stimulation of the LC can augment reward-related extinction. Optogenetic inhibition of the LC during extinction trials reduced responding during the trials where it was applied, but no long-lasting changes in the retention of extinction were observed. Since not all LC cells expressed halorhodopsin, it is possible that more complete LC inhibition or pathway-specific targeting would be more effective at suppressing extinction learning. These results provide further insight into the neural basis of appetitive extinction, and in particular the role of the LC. A deeper understanding of the physiological bases of extinction can aid development of more effective extinction-based therapies.
Touch receptor end-organ innervation and function require sensory neuron expression of the transcription factor Meis2
Authors: Desiderio Simon , Schwaller Frederick , Tartour Kevin , Padmanabhan Kiran , Lewin Gary R , Carroll Patrick , Marmigere Frederic
Published: February 2024

Touch sensation is primarily encoded by mechanoreceptors, called low-threshold mechanoreceptors (LTMRs), with their cell bodies in the dorsal root ganglia. Because of their great diversity in terms of molecular signature, terminal endings morphology, and electrophysiological properties, mirroring the complexity of tactile experience, LTMRs are a model of choice to study the molecular cues differentially controlling neuronal diversification. While the transcriptional codes that define different LTMR subtypes have been extensively studied, the molecular players that participate in their late maturation and in particular in the striking diversity of their end-organ morphological specialization are largely unknown. Here we identified the TALE homeodomain transcription factor Meis2 as a key regulator of LTMRs target-field innervation in mice. Meis2 is specifically expressed in cutaneous LTMRs, and its expression depends on target-derived signals. While LTMRs lacking Meis2 survived and are normally specified, their end-organ innervations, electrophysiological properties, and transcriptome are differentially and markedly affected, resulting in impaired sensory-evoked behavioral responses. These data establish Meis2 as a major transcriptional regulator controlling the orderly formation of sensory neurons innervating peripheral end organs required for light touch.
Essential Function of Transmembrane Transcription Factor MYRF in Promoting Transcription of miRNA lin-4 during C. elegans Development
Authors: Xu Zhimin , Wang Zhao , Wang Lifang , Qi Yingchuan B.
Published: February 2024

Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In
C. elegans
, the microRNA
lin-4
critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation of
lin-4
expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary for
lin-4
activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with
lin-4
expression timing. MYRF-1 regulates
lin-4
expression cell-autonomously and hyperactive MYRF-1 can prematurely drive
lin-4
expression in embryos and young first-stage larvae. The tandem
lin-4
promoter DNA recruits MYRF-1
GFP
to form visible loci in the nucleus, suggesting that MYRF-1 directly binds to the
lin-4
promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of
lin-4
expression.
Remodeling of skeletal muscle myosin metabolic states in hibernating mammals
Authors: Lewis Christopher TA , Melhedegaard Elise G , Ognjanovic Marija M , Olsen Mathilde S , Laitila Jenni , Seaborne Robert AE , Gronset Magnus , Zhang Changxin , Iwamoto Hiroyuki , Hessel Anthony L , Kuehn Michel N , Merino Carla , Amigo Nuria , Frobert Ole , Giroud Sylvain , Staples James F , Goropashnaya Anna V , Fedorov Vadim B , Barnes Brian , Toien Oivind , Drew Kelly , Sprenger Ryan J , Ochala Julien
Published: February 2024

Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus. We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus, changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20 °C). Upon repeating loaded Mant-ATP chase experiments at 8 °C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77–107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus, which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.
Beneficial endophytic fungi improve the yield and quality of Salvia miltiorrhiza by performing different ecological functions
Authors: Li Xiaoyu , Lin Yali , Qin Yong , Han Guiqi , Wang Hai , Yan Zhuyun
Published: February 2024

Background

Endophytic fungi can enhance the growth and synthesis of secondary metabolites in medicinal plants. Salvia miltiorrhiza Bunge is frequently employed for treating cardiovascular and cerebrovascular ailments, with the primary bioactive components being salvianolic acid and tanshinone. However, their levels in cultivated S. miltiorrhiza are inferior to that of the wild herbs, so the production of high-quality medicinal herbs is sharply declining. Consequently, the utilization of beneficial endophytic fungi to improve the yield and quality of S. miltiorrhiza holds great significance for the cultivation of medicinal plants.

Methods

In this study, nine non-pathogenic, endophytic fungal strains were introduced into sterile S. miltiorrhiza seedlings and cultivated both in vitro and in situ (the greenhouse). The effects of these strains on the growth indices, C and N metabolism, antioxidant activity, photosynthesis, and content of bioactive ingredients in S. miltiorrhiza were then evaluated.

Results

The results showed that the different genera, species, or strains of endophytic fungi regulated the growth and metabolism of S. miltiorrhiza in unique ways. These endophytic fungi primarily exerted their growth-promoting effects by increasing the net photosynthetic rate, intercellular CO2 concentration, and the activities of sucrose synthase, sucrose phosphate synthase, nitrate reductase, and glutamine synthetase. They also enhanced the adaptability and resistance to environmental stresses by improving the synthesis of osmoregulatory compounds and the activity of antioxidant enzymes. However, their regulatory effects on the growth and development of S. miltiorrhiza were affected by environmental changes. Moreover, the strains that significantly promoted the synthesis and accumulation of phenolic acids inhibited the accumulation of tanshinones components, and vice versa. The endophytic fungal strains Penicillium meloforme DS8, Berkeleyomyces basicola DS10, and Acremonium sclerotigenum DS12 enhanced the bioaccumulation of tanshinones. Fusarium solani DS16 elevated the rosmarinic acid content and yields in S. miltiorrhiza. The strain Penicillium javanicum DS5 improved the contents of dihydrotanshinone, salvianolic acid B, and rosmarinic acid. The strains P. meloforme DS8 and B. basicola DS10 improved resistance.

Conclusion

Various endophytic fungi affected the quality and yield of S. miltiorrhiza by regulating different physiological and metabolic pathways. This study also provides a novel and effective method to maximize the effects of beneficial endophytic fungi by selecting specific strains to design microbial communities based on the different ecological functions of endophytic fungi under varying environments and for specific production goals.
Remote Work Ergonomics and Musculoskeletal Health in Lagos, Nigeria: A Cross-sectional Study
Authors: Opone Anwulika Laura , Douglas Kingsley , Wejie-Okachi Chinunam
Published: February 2024

Remote workers are at risk of musculoskeletal disorders due to the sedentary nature of their work and ergonomic safety compliance is a necessary control measure. This work evaluated ergonomic compliance and work-related musculoskeletal disorders among fully remote workers in Lagos. Following approval, 371 remote workers were recruited to participate in a cross-sectional study. They responded to a Questionnaire, the main study tool, which biodata, work information, knowledge of ergonomics, workstation compliance, level of support offered by employer to aid ergonomic compliance, behavioral factors, musculoskeletal disorder symptoms and medical Information regarding past and present diagnosis/ treatment. To support data on workspace compliance, physical and virtual observations were carried out on 361 workspaces. Collated data were analyzed using descriptive tools. The data analysis showed that a large percentage of remote workers, about 66.31% had high knowledge on ergonomics. However, a relatively lower percentage, about 23.36% had highly compliant workspaces. Only 8% were highly compliant based on behavioral patterns as a larger 48% fell into the low category. The study showed that only 15.36% of employers gave a very high level of support to encourage ergonomic compliance. The Most prevalent musculoskeletal disorder amongst the population studies is the lower back pain, which has been suffered by 90.5% of respondents at varying durations and levels. This was closely followed by the upper back pain at 85.7% then eye pain at 47.1. The study shows a positive correlation between Employer support and: ergonomic compliance based on workspaces, ergonomic compliance based on behavioral patterns as well as knowledge on ergonomics at 0.26828222, 0.151881985 and 0.188086546 respectively. There is an urgent need to educate employees on ergonomic safety, create effective occupational health plans tailored specifically for the remote work model, develop feasible measures for compliance checks, and work with authorities to enact laws to protect the health and safety of remote workers in the long run.
A giant right atrial myxoma: Case report
Authors: Özpinar Cevat , Ceran Sami , Yeniterzi Mehmet , Yüksek Tahir , Özergin Ufuk , Solak Hasan
Published: August 2005

Right atrial myxomas have rarely been reported. The authors describe a giant hourglass-shaped atrial myxoma consisting of three lobes; one of them had protruded into the right ventricle. Its size was 18×7×5 cm and weight was 170 g. The authors were not able to find another myxoma as big as this one in the literature, so they are reporting it. They review and discuss the literature involving the subject.
Endoscopic intervention for enteral access
Authors: Stellato Thomas A.
Published: August 2005

Contrary to total parenteral nutrition with its relatively recent introduction into modern clinical medicine, enteral nutrition has a long and colorful history. Prior to development of fiberoptic endoscopy, physicians attempting to feed patients who could not or would not eat were limited to the blind placement of intestinal tubes or radiologically assisted placement of these devices. Previous to these modern attempts, the use of nutrient enemas was attempted for which there was evidence of occasional success. With the introduction of fiberoptic flexible endoscopy, guidance of tubes into the upper intestinal tract under direct vision became feasible. The manner in which tubes were positioned, advanced, or manipulated are myriad and attest to the ingenuity of clinicians. A revolution in endoscopic intervention occurred with the introduction of the percutaneous endoscopic gastrostomy in 1980. This provided secure access to the stomach without a laparotomy. This technique was also modified to allow decompression of the stomach with feeding distally into the small intestine and also direct puncture and placement of tubes into the small intestine. The most recent advance in enteral nutrition is taking place at the present time with the introduction of laparoscopic techniques in the creation of gastrostomies and jejunostomies.
Therapeutic colonoscopy
Authors: Forde Kenneth A.
Published: August 2005

Therapeutic colonoscopy has replaced or lessened to a significant degree the need or extent of traditional open surgical procedures. The common uses of therapeutic colonoscopy are hemostasis, resection and ablation of benign and malignant disease, decompression and recanalization of obstructed or dilated bowel, as well as foreign body extraction. Bleeding from arteriovenous and other vascular abnormalities can be controlled with 40% to 80% success rates using endoscopically delivered, monopolar, bipolar, or laser coagulation. The palliation of bleeding recurrent or inoperable colorectal cancer is achieved in up to 90% of patients. Virtually all pedunculated adenomas and most sessile adenomas are regularly removed colonoscopically, while large and recurrent villous adenomas in high risk individuals can be successfully managed by endoscopically delivered laser ablation techniques. Emergency colonoscopic reduction of sigmoid volvulus is performed pre‐operatively and decompression of the dilated colon of non‐obstructive colonic ileus is now regularly achieved. Colonic strictures have been dilated with a variety of techniques ranging from divulsion with through‐the‐scope balloon dilators to laser recanalization. Pre‐operative endoscopic laser relief of tumor obstruction is employed to avoid preliminary or decompressing colostomy. Endoscopic laser debulking and recanalization of recurrent or inoperable cancer has been achieved with up to 80% success and various foreign bodies may be extracted from the colon with a number of endoscopic techniques. The morbidity of therapeutic colonoscopy has ranged from 1% to 2% for polypectomy to 11% for laser palliation of bleeding from advanced cancer, often with obstruction.
Endoscopic therapy for biliary obstruction
Authors: Soehendra Nib , Binmoeller Kenneth F. , Grimm Horst
Published: August 2005

Endoscopic management of biliary obstruction is feasible in most patients and has emerged as standard treatment. Aside from the removal of bile duct stones, placement of a biliary stent is the most commonly employed modality of management. In experienced hands, this is successful in over 90% of patients. Lower procedure‐related complications and the relative non‐invasive nature of endoscopic treatment has relegated surgical manement to a subsidiary role. Hospitalization time rarely exceeds 1–2 days. In most patients with advanced malignant disease and short life expectancy, stenting affords effective palliation. For the majority of patients endoscopic management is preferable to the percutaneous transphepatic approach due to lower overall mortality and morbidity. Stent occlusion necessitating replacement remains a problem, but improvements in this area can be expected. New plastic stent designs are undergoing investigation. Expandable metallic stents are promising but controlled comparative trials with conventional plastic prostheses are needed. Use of expandable stents should be judicious since these cannot be removed. In the future we can look forward to advances in peroral cholangioscopic technology which may permit targeted treatment of intraductal biliary malignancies.
Gastrointestinal motility of patients with Roux‐en‐Y reconstruction
Authors: Coelho Julio C. U. , Clemente Luiz , Matias Jorge E. F. , Campos Antonio C. L. , Wiederkehr Julio C.
Published: August 2005

The electromyographic activity of the gastrointestinal tract was studied in 28 patients undergoing gastric, biliary, and pancreatic operations with reconstruction of the gastrointestinal tract with a Roux‐en‐Y limb. The Roux‐en‐Y limb was constructed 1 to 5 years before the study in 8 patients (chronic Roux‐en‐Y) and at the operation in which the electrodes were implanted in 20 patients (recent Roux‐en‐Y). All four phases of the migrating motor complex (MMC) were identified in the gastrointestinal tract, including in the Roux‐en‐Y limb. The duration of the MMC was 82.4 ± 22.3 min in the patients with chronic Roux‐en‐Y and 89.0 ± 25.1 min in the patients with recent Roux‐en‐Y. Food ingestion converted the MMC to the fed pattern in the entire gastrointestinal tract, including the Roux‐en‐Y limb in 16 (76.2%) of 21 recordings of the patients with chronic Roux‐en‐Y and in 27 (84.4%) of 32 recordings of the patients with recent Roux‐en‐Y. The duration of the fed pattern was 170 ± 34 min in the patients with chronic Roux‐en‐Y and 154 ± 26 min in the patients with recent Roux‐en‐Y. The findings of this study indicate that the electromyographic activity of the Roux‐en‐Y limb is normal during both fasting and fed states, even many years after the construction of the Roux‐en‐Y.
Optimization of isolated hyperthermic limb perfusion
Authors: Omlor G. , Gross G. , Ecker K. W. , Burger I. , Feifel G.
Published: August 2005

During isolated limb perfusion, we studied the impact of limb temperature on the concentration of cytostatic drugs in the tissue to identify a possible selective absorption of cytostatic agents by the various tissues. Ten consecutive patients with malignant melanoma were randomly divided into two different groups and perfused with 1 mg cisplatin per kg body weight. In one group the cytostatic agents were injected under hyperthermic conditions (39.5°C) and in the other group under normothermic conditions (37°C). The platinum concentration in the melanoma was twice as high in the hyperthermic group as in the group under normothermic conditions. In the tumor‐free tissue the platinum concentration decreased with temperature while it remained constant in the musculature. This selective concentration of cisplatin in the tumor under hyperthermic conditions is accompanied by fewer side effects. Follow‐up will show whether the oncological results will be improved in the hyperthermic conditions as one might expect.
Prostacyclin release from the human saphenous vein in diabetics is lower than in nondiabetics
Authors: Brunkwall Jan S. , Bergqvist David
Published: August 2005

The balance between prostacyclin and thromboxane has been suggested to be of great importance for the maintenance of patency in veins. In order to investigate prostacyclin and thromboxane release, segments from the human saphenous veins were investigated in 53 patients. Twenty‐seven patients (10 males, 17 females) underwent surgery for varicose veins. Twenty‐six patients (14 nondiabetics, 12 diabetics) underwent surgery for lower limb ischemia (rest pain or gangrene) with use of the saphenous vein as arterial conduit. Vein segments were gently excised and perfusedex vivo for five 15 minute periods, with a balanced salt solution and determination of the stable degradation products 6‐keto‐PGF1α and TxB2. Saphenous veins from patients with varicose veins had an initial prostacyclin release of 61 ± 13 pg/mm2/15 min declining to 4 ± 1 pg/mm2/15 min after 60 min (p<0.001) and increasing after addition to arachidonic acid to 37 ± 7 pg/mm2/15 min (p<0.001). Segments from nondiabetic patients with lower limb ischemia did not differ from those of varicectomy patients, but diabetic segments had a significantly lower prostacyclin release than both these groups, 34 ± 11 pg/mm2/15 min, 1 ± 1 pg/mm2/15 min, and 7 ± 5 pg/mm2/15 min, respectively (p<0.05). The addition of arachidonic acid failed to increase the prostacyclin release in diabetics. Three patients from each group were studied regarding thromboxane release and there was almost no detectable thromboxane in any group. These findings suggest that diabetics have a lowered prostacyclin release from the saphenous vein and that the deficiency is at the cyclo‐oxygenase level. The results could be of importance in thrombogenesis.
Mutational activation of RAS and GSP oncogenes in differentiated thyroid cancer and their biological implications
Authors: Goretzki Peter E. , Lyons John , Stacy‐Phipps Sandrina , Rosenau Werner , Demeure Michael , Clark Orlo H. , McCormick Frank , Röher Hans‐Dietrich , Bourne Henry R.
Published: August 2005

Activating mutations of ras‐genes (Kirsten‐ras, Harvey‐ras, N‐ras) and genes encoding for the alpha subunit of G‐proteins (Gs, Gi2, Gi3, Go, Gz) were assessed in 32 differentiated thyroid cancer (DTC) tissues from German (n=22) and American (n=10) patients. Gs‐protein (GSP) and/or ras mutations were found in 69% of all tissues with a heterogeneous distribution pattern. An increased prevalence could be demonstrated in metastatic (8 of 9 mutation positive) when compared to localized disease (13 of 23 mutation positive) (p<0.001) and in patients >50 years of age (16 of 18 mutation positive), when compared to younger patients (6 of 14 mutation positive) (p<0.001). No activating mutations were found on H‐ras and K‐ras genes nor on genes encoding for the alpha subunits of Gi2, Gi3, Go, and Gz. Differentiated thyroid cancer tissue from German patients revealed a higher prevalence for GSP mutations (73%) than did DTC from American patients (20%) (p<0.001). We demonstrated a high frequency of ras and GSP mutations in DTC and suggest that these mutations may contribute to our basic understanding of this disease and might initiate a new search for more rational and individualized therapeutic approaches in patients with DTC.
Pancreatic tumors in multiple endocrine neoplasia type 1: Clinical presentation and surgical treatment
Authors: Grama D. , Skogseid B. , Wilander E. , Eriksson B. , Mårtensson H. , Cedermark B. , Ahrén B. , Kristofferson A. , Öberg K. , Rastad J. , Åkerström G.
Published: August 2005

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN‐1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non‐functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long‐erm outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non‐functioning lesions. Nine patients died from progressive tumor disease during follow‐up. Consistent with previous studies, we found that surgery is indicated in MEN‐1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors. This strategy should be applied especially in patients with aggressive family histories to possibly reduce the risk of malignant tumor progression.
Clinical course and thyroid stimulating hormone (TSH) receptor antibodies during surgical treatment of Graves' disease
Authors: Mori Yoko , Matoba Naoya , Miura Shunji , Sakai Nobumitsu , Taira Yukio
Published: August 2005

This study assessed the results of surgical treatment for Graves' disease in our hospital and examined the relationship between the values of thyroid stimulating hormone (TSH) receptor antibodies and postoperative thyroid function. From 1983 to 1988, subtotal thyroidectomy was performed in 313 patients with Graves' disease. The follow‐up rate was 89.1% (278 of 313 patients). Thirteen (4.2%) patients required methimazole postoperatively for hyperthyroidism and 23 (7.3%) patients required L‐thyroxine postoperatively for hypothyroidism. The relationship between the postoperative thyroid function and TSH receptor antibodies was examined.

The pre‐operative thyrotropin binding inhibitory immunoglobulin (TBII) value had no relationship to postoperative thyroid function. Only in the patients who were hyperthyroid postoperatively did the TBII value remain elevated, but the value decreased gradually in patients who were not hyperthyroid postoperatively. In 43 of 94 patients whose pre‐operative TBII values were high, the postoperative TBII value normalized. The higher the preoperative TBII value, the longer time was required for it to normalize postoperatively. The postoperative thyroid stimulating antibody (TSAb) values were higher in patients who remained hyperthyroid than in the patients who were not hyperthyroid. In the patients who remained hyperthyroid postoperatively, there was a significant correlation between the postoperative TBII value and the TSAb value. In the patients who were hypothyroid postoperatively, the TSBAb values were negative.

In patients undergoing surgical treatment of Graves' disease, the postoperative TBII and TSAb values were related to postoperative hyperthyroidism. The TSBAb value had no relationship to postoperative hypothyroidism.
Unilateral neck exploration for primary hyperparathyroidism: Analysis of a controversy using a mathematical model
Authors: Duh Quan‐Yang , Udén Per , Clark Orlo H.
Published: August 2005

Most endocrine surgeons explore both sides of the neck and identify all parathyroid glands when operating on patients with primary hyperparathyroidism. Others, however, advocate the unilateral approach, i.e., if an adenoma and a normal gland are identified, the contralateral side is not explored. We analyzed the strategy of the unilateral approach using a mathematical model to determine the variables that influence the probability of missing a tumor on the unexplored side of the neck. Assuming the frequency of single adenoma is 80%, hyperplasia 14%, double adenomas 4%, triple adenomas 1%, and carcinoma 1%, and the probability of missing a tumor on the explored side is 5%, we found that: 1. Only 41% of the patients treated by the unilateral approach undergo unilateral exploration. This is increased to 62% when a localization study with a sensitivity of 80% is used pre‐operatively. 2. The probability of missing a tumor on the unexplored side of the neck parallels the prevalence of multiple adenomas. Half of the patients with triple adenomas and two‐thirds of the patients with double adenomas will have a missed tumor when treated by the unilateral approach. 3. Patients who undergo unilateral exploration have an additional 7% to 8% probability of missing a tumor that would have been found if bilateral exploration is performed. This risk is lowered to 2% by a pre‐operative localization study that is 80% sensitive. 4. A prospective study will require 684 patients, randomized to the unilateral or bilateral approach, to have an 80% statistical power (α=0.05, β=0.20) of detecting a difference between a 5% and a 10% risk of missing a tumor.
Urodynamics in patients with pheochromocytoma: A peri‐operative study of 10 cases
Authors: Carnaille B. M. , Rigot J. M. , Bailleul J. P. , Quievreux J. L. , Wemeau J. L. , Proye C. A.
Published: August 2005

Alpha receptors have been demonstrated in the bladder neck, and urinary retention may be the presenting symptom in an occasional pheochromocytoma patient. This prompted us to definie the urodynamic profile in pheochromocytoma patients. Ten patients were studied. Except for 2 patients, all tumors secreted norepinephrine either alone (n=4) or mixed (n=4). Urodynamic studies (uroflowmetry, cystometry, profilometry, response to alpha‐adrenergic agents) were performed with Urodyn 5000 chain (DANTEC) connected to a water perfused Bohler's catheter. Profilometry was done according to the Brown and Wickham technique. Normal values were those of the International Continence Society. Alpha blocker test was done by intravenous injection of thymoxamine (0.5 mg/kg) and was considered as positive if urethral closure pressure (UCP) decrease was >30% after 10 minutes. Ten patients had a pre‐operative study, omitting alpha‐blocker test in 1 patient; 5 patients consented a postoperative study. Pre‐operatively we could demonstrate: 1) Increased UCP in 8 of 10 patients, regardless of the secretory pattern; 2) Response to alpha‐adrenolytic agents in 7 of 9 patients; and postoperatively: 3) Good correlation between a positive alpha‐blocker test and a decrease in urethral pressure in 3 of 5 patients. Urodynamics in pheochromocytoma patients show a typical alpha‐adrenergic pattern and may explain bladder dysfunction as a presenting symptom.
Adrenalectomy in primary aldosteronism: A long‐term follow‐up study in 52 patients
Authors: Favia Gennaro , Lumachi Franco , Scarpa Vincenza , D'Amico Davide F.
Published: August 2005

From 1975 to 1989, 52 patients with primary adolsteronism underwent adrenalectomy. There were 16 men and 36 women. The average age was 42.5 years, ranging from 28 years to 70 years. They were all hypertensive, with average pre‐operative diastolic pressures varying from 105 to 140 mm Hg (median 117 mm Hg). The subjective symptoms most frequently reported were headache (71%) and asthenia (53%). In all patients except two, serum potassium concentration was 3.3 mEq/L (median 2.7 mEq/L) at the time of diagnosis. Plasma aldosterone concentration was elevated in all patients, 48±5.3 ng/mL in the recumbent position and 52.6±6.0 ng/mL in the upright position. The operations carried out were 50 unilateral and 2 bilateral adrenalectomies. In 4 patients a transperitoneal approach was employed and in the remaining 48 patients an extraperitoneal flank incision was used. The histological findings were 47 adenomas (with dimension ranging from 1 to 4.5 cm), unilateral macronodular hyperplasia in 2 patients, an adenoma plus controlateral hyperplasia in 1 patient, bilateral hyperplasia in 1 patient, and unilateral hyperplasia in 1 patient. After long‐term follow‐up (median 77 months, range 13 to 189 months), 15 patients remained hypertensive (diastolic blood pressure up to 100 mm Hg). In 9 of these patients the hypertensive illness had been present for more than 5 years prior to operation. In the remaining 37 (71%) patients, the arterial pressure returned to normal and in almost half of the patients this result was evident one or two days after operation.
The role of epinephrine, norepinephrine, and dopamine in blood pressure disturbances in patients with pheochromocytoma
Authors: Ito Yukio , Fuimoto Yoshihide , Obara Takao
Published: August 2005

Fifty‐six patients with pheochromocytoma underwent surgery during the 9‐year period from 1981 to 1990. These patients were divided into two groups according to whether the dominant plasma concentration was of epinephrine or norepinephrine. Plasma levels of the catecholamines were stratified into three grades at 5 and 10 times the normal upper limit. Pre‐operative disturbances of blood pressure, sustained or paroxysmal, and normal blood pressure were highly correlated with the dominantly secreted catecholamine and its plasma concentration. Thirteen patients with high plasma norepinephrine levels (≥10 times normal) had sustained hypertension while 18 patients with moderate to high plasma epinephrine levels (≥5 times normal) had paroxysmal hypertension. In the majority of normotensive patients (12 of 14), plasma catecholamine levels were <10 times the upper normal limit. Urinary excretion of dopamine and size of the tumor were analyzed according to these patient groups. In the norepinephrine dominant group, urinary dopamine excretion tended to be proportional to the plasma epinephrine levels and when the patients were normotensive, urinary dopamine excretion decreased. In norepinephrine‐secreting patients, urinary dopamine tended to be inversely correlated with the plasma norepinephrine level; however dopamine did not prevent the hypertensive action of norepinephrine. Tumor size showed no correlation with the plasma levels of catecholamine in the moderate to high plasma catecholamine groups. We conclude that the plasma catecholamine type and its level are the most important factors in determining the patterns of blood pressure disturbances of patients with pheochromocytoma.
Surgery for hyperthyroidism: Hemithyroidectomy plus contralateral resection or bilateral resection? A prospective randomized study of postoperative complications and long‐term results
Authors: Andåker L. , Johansson K. , Smeds S. , Lennquist S.
Published: August 2005

Fifty consecutive patients undergoing surgical treatment for hyperthyroidism were randomized to have either bilateral subtotal resection (n=23) or hemithyroidectomy plus contralateral resection (n=27). No significant differences in operating time or intra‐operative bleeding were found. No postoperative bleeding and no temporary or persistent recurrent laryngeal nerve paralysis occurred. Four patients who underwent bilateral resection and 2 patients who had hemithyroidectomy resection needed temporary calcium supplementation, and the serum calcium concentrations were slightly lower during the first few postoperative days in the patient undergoing hemithyroidectomy/resection. No persistent hypocalcemia occurred in either of the groups. At follow‐up 3–4 years (mean 3.6 years) postoperatively, 1 patient in the bilateral resection group developed recurrent hyperthyroidism; no patients in the hemithyroidectomy/resection group developed recurrent hyperthyroidism. Twelve (44%) patients in the hemithyroidectomy/resection group and 8 (35%) patients in the bilateral resection group needed thyroxine supplementation because of a rise in thyroid stimulating hormone concentration combined with clinical signs of hypothyroidism that developed during follow‐up. Hyperthyroidism can be treated by hemithyroidectomy plus contralateral resection without increasing the risk of complications. The results also suggest that when using this method, a slightly larger thyroid remnant should be left to avoid an increase in the incidence of hypothyroidism postoperatively.
Rare variants of malignant melanoma
Authors: Milton G. W. , Shaw H. M.
Published: August 2005

The personal experience with 5 rare types of malignant melanoma is reviewed to point out some of the practical problems in the diagnosis and management of these tumors. The rare forms discussed are conjunctival, nasal, oral, vulvar, and penile melanomas. All pigmented lesions in the oral cavity, but not the penis or vulva, should be prophylactically excised as lesions in the mouth have a higher malignant potential. Local excision of all 5 forms of primary melanomas, no matter how locally advanced they may be, is the sole treatment. Nevertheless, anatomic constraints often preclude surgery with generous margins and consequently local recurrence, particularly for conjunctival, nasal, and oral primary lesions, is usually the major first failure in treatment. Lymph node dissection is only performed if the regional nodes are palpable at the time of first presentation. Elective lymph node dissections are not performed since the patients are often elderly, the lymphatic drainage is usually ambiguous or multiple, and the disease tends to spread hematogenously rather than lymphatically. Surgery still remains the cornerstone of treatment for these rare forms of melanoma but prognosis is very poor since surgery is often a palliative rather than a curative measure. Improved survival may depend on identifying more effective chemotherapeutic and immunologic agents.
Malignant melanoma in childhood: A clinicopathologic study of 13 cases and comparison with spitz nevi
Authors: Crotty Kerry A. , McCarthy Stanley W. , Palmer Alexander A. , Ng Alan B. P. , Thompson John F. , Gianoutsos Mark P. , Shaw Helen M.
Published: August 2005

The clinical and histological features of 13 malignant melanomas in children <13 years of age in New South Wales, Australia, were compared with those in a control group of children with 15 Spitz nevi, 4 of which were considered atypical, and 2 unusual compound nevocellular nevi. Six of the controls had been previously diagnosed histologically as malignant melanoma. The objective observations made by one or more histopathologists experienced in reporting melanocytic lesions, and the clinical details, mainly from the Sydney Melanoma Unit files, were entered on a detailed protocol. Evaluation was assisted by the use of SPSS‐X software on a mainframe VAX computer. Six of the 13 children with malignant melanoma died with their disease. The most frequent clinical features found in the malignant melanomas were bleeding, ulceration, itching, and black or variegated color. Recent enlargement and darkening were noted in the majority of both the malignant melanomas and the Spitz nevi. Histological features favoring malignancy in this series were mitoses within 0.25 mm of the dermal margin of the melanoma, a dermal mitotic rate exceeding 2/mm2, ulceration, surface exudate, large pigment granules, and clear‐cell differentiation. The median thickness of the malignant melanomas was 1.3 mm but in the 4 children who died with melanoma the median thickness was 2.9 mm. Absence of mitoses, predominance of spindle cells, and diffuse maturation favored Spitz nevus. The median thickness of the Spitz nevi was 0.7 mm.
Palliative care and melanoma: The care of the patient with progressive disease
Authors: Lickiss J. N.
Published: August 2005

The World Health Organization has taken the lead in recent years in encouraging an appropriate focus on palliative care which includes but goes beyond terminal care. Comprehensive care of patients with advanced progressive disease requires increased emphasis, with adequate resources. Management of major symptoms is a crucial component of such a care program and requires the application of recent advances in palliative therapeutics (notably but not only good quality pain management), whether or not direct antitumor strategies are being continued. The choice of treatment approaches must be related to the patient's personal priorities.
Who benefits from antireflux surgery?
Authors: Stein Hubert J. , DeMeester Tom R.
Published: August 2005

Prior to any rational therapy of gastro‐esophageal reflux disease, an objective diagnosis of the presence and the cause of the disease are necessary. Gastro‐esophageal reflux disease, i.e., increased esophageal exposure to gastric juice, can be due to a mechanically defective lower esophageal sphincter, inefficient esophageal clearance of refluxed gastric contents, and abnormalities of the gastric reservoir that augment physiologic reflux. Antireflux surgery is designed to correct a mechanically defective sphincter, i.e., a sphincter with a mean pressure below 6 mm Hg, a mean length exposed to the positive pressure environment of the abdomen of less than 1 cm, or a mean overall length of less than 2 cm. In our experience, this is found in approximately 50% to 60% of patients with gastro‐esophageal reflux disease. Antireflux surgery is not indicated in patients with increased esophageal exposure to gastric juice secondary to ineffective clearance or gastric abnormalities. Consequently, the indications to proceed with an antireflux procedure are persistent or recurrent symptoms and/or complications of gastro‐esophageal reflux disease after 8 to 12 weeks of intensive acid suppression therapy, the objective documentation of increased esophageal exposure to gastric juice with 24 hour esophageal pH monitoring, and the presence of a mechanically defective lower esophageal sphincter on manometry. In patients selected according to these criteria, Nissen fundoplication provides effective relief of reflux symptoms in 91% of patients with more than 10 year follow‐up.
Mechanisms of action of antireflux surgery: Theory and fact
Authors: Little Alex G.
Published: August 2005

Despite the absence of definitive explanations regarding either the physiologic or surgical factors which curtail gastro‐esophageal reflux, effective antireflux operations exist. This article explores the theoretical factors relevant to the surgical control of reflux. These theoretical features include: (1) the pressure, length, and location of the manometrically defined lower esophageal sphincter (LES); (2) the gastro‐esophageal valve as defined by the angle of His and a mucosal flap valve; and (3) the mechanical effects of a fundoplication which serve to increase the opening pressure of the cardia and optimize the physical relationships described by the law of La Place. Finally, the relation of these theoretical factors to actual operations is discussed.