Autosomal dominant inheritance in adiposis dolorosa (Dercum's disease)

Summary A family in which 5 members were affected with adiposis dolorosa (Dercum's disease) is reported. The pedigree analysis gives evidence of autosomal dominant inheritance.

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Zusammenfassung Es wird eine Familie beschrieben, in welcher 5 Mitglieder von Adipositas dolorosa (Dercumsche Erkrankung) befallen waren. Der Erbgang ist autosomal-dominant.

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This work was partially supported by a grant from the Ford Foundation.     

Focus: Rare Disease: Differential Diagnosis of a Case of Dercum’s Disease with Possible Familial Involvement and Review of Literature

Dercum’s disease (DD), also described as adiposis dolorosa, is a poorly understood and rare adipose tissue disorder involving obesity and painful adipose tissue masses. Patients may have associated bruising and constitutional symptoms such as fatigue, difficulty concentrating, and sleep disturbance. DD was initially described in 1888 by Francis Xavier Dercum, and was classified into four subtypes, including generalized diffuse, generalized nodular, localized nodular, and juxta-articular subtypes. While this disease has been described for more than 130 years, its etiology and treatment remain elusive. We describe a case of a patient with DD who presented to Ochsner Medical Center, New Orleans, LA, for evaluation of treatment options. We review current knowledge on this rare disease and data on modern treatment methods.     

A method for bulbospinal trigeminal nucleotomy in the treatment of facial deafferentation pain

Many types of facial pain are difficult to treat, such as postherpetic, posttraumatic, or pain following denervation procedures used in the treatment of trigeminal neuralgia (anesthesia dolorosa), all of which involve deafferentation of the spinal trigeminal nucleus.     

Fatty acid synthase: A metabolic oncogene in prostate cancer?

In 1920, Warburg suggested that tumors consistently rely on anaerobic pathways to convert glucose to ATP even in the presence of abundant oxygen [Warberg, 1956] despite the fact that it is less efficient for energy supply than aerobic glycolysis. The reasons for this remain obscure to date. More often than not, the microenvironment of solid tumors contains regions of poor oxygenation and high acidity. In this context hypoxia can act in an epigenetic fashion, inducing changes in gene expression and in metabolism for survival. It is reasonable to assume that only the tumor cells capable of developing an unusual tolerance to limiting oxygen availability and to the acidosis resulting from excessive lactate production, can survive. In addition to the striking changes that occur in glucose metabolism, studies in human cancer patients suggest that there is often also an increase in free fatty acid turnover, oxidation and clearance [Legaspi et al., 1987; Hyltander et al., 1991]. For instance, a lipid mobilizing factor produced by tumor cells appears to be responsible for the increase in whole body fatty acid oxidation [Russell and Tisdale, 2002]. Fatty acids synthesis in tumor tissues also occurs at very high rates, as first demonstrated more than half a century ago [Medes et al., 1953]. Importantly, (14)C glucose studies have shown that in tumor cells almost all fatty acids derive from de novo synthesis despite adequate nutritional supply [Sabine and Abraham, 1967; Ookhtens et al., 1984; Weiss et al., 1986]. In addition, tumors overexpressing fatty acid synthase (FAS), the enzyme responsible for de novo synthesis of fatty acids, display aggressive biologic behavior compared to those tumors with normal FAS levels, suggesting that FAS overexpression confers a selective growth advantage. Here, we will review the roles that FAS plays in important cellular processes such as apoptosis and proliferation. In addition, speculations on the putative role of FAS in the altered metabolic pathways of prostate cancer cells will be explored. Because of the frequent overexpression of this enzyme prostate cancer, FAS constitutes a therapeutic target in this disease.     

A brainstem "mini-discharge" syndrome (anesthesia dolorosa)

Chronic pain consisting of anesthesia dolorosa secondary to bilateral interruption of the trigeminal nerves is presented as a brain stem reticular denervation syndrome. Electrothalamograms revealed fast frequency discharges in the mesothalamic prerubral and centermedian reticular formation. Mesothalamic electrical stimulation attenuated the discharges. Pain and other symptoms presumably of brainstem origin also were attenuated or abolished by therapeutic electrical stimulation twice daily. It is postulated that brain stem-represented behavioral generators are implicated by the reticular discharges in order to produce the complex symptomatology. Consequently the symptom complex is collectively identified as a brainstem "mini-discharge" syndrome. A theoretical discussion is presented to defend the thesis that reticular denervation-induced low threshold discharge system accounts for the episodic states of pain, dyskinesia, mood, and memory disturbances.     

Unusual medium-chain polyunsaturated fatty acids from the snow alga Chloromonas brevispina

The gas chromatography-mass spectrometry (GC-MS) method was used to identify unusual medium-chain polyunsaturated fatty acids (PUFAs) in the snow alga Chloromonas brevispina collected in 2006 from surface layers of a snow field with conspicuous green patches in Bohemian Forest (Czech Republic). PUFAs formed more than 75% total fatty acids. Among them, mass spectroscopy of picolinyl esters showed sizable proportions of medium-chain PUFA, e.g., 5,8,11-tetradecatrienoic and 6,9,12-pentadecatrienoic acids. The high relative content of PUFA indicates that PUFA are an important element ensuring cell survival. Our report appears to be the first to describe the presence of short- and medium-chain PUFAs in green psychrophilic algae of the genus Chloromonas.     

Multiple glomus tumors associated with arteriovenous fistulas and with nodular lesions of the finger joints.

A patient is reported with an extremely unusual clinical presentation comprising painful subungual glomus tumors, hemangioma-like skin lesions of the trunk, and nodular lesions of the finger joints. Prominent arteriovenous shunting also was present. The etiology of all these abnormalities was thought to be extensive proliferation of glomus cells.     

Postoperative analgesia: a comparison of intravenous on-demand fentanyl with epidural bupivacaine.

In a randomised trial postoperative pain relief was provided by either epidural injections of bupivacaine or an infusion of fentanyl adjusted by the patient to achieve adequate pain relief. Both techniques produced satisfactory analgesia without respiratory depression after peripheral arterial surgery. The technique of infusing intravenously a potent analgesic in a dose adjusted by the patient appears to offer several advantages in postoperative care.     

Hormonal and Metabolic Studies in Pheochromocytoma

One patient with benign and another with malignant pheochromocytoma have been studied in an attempt to elucidate the effect of increased catecholamines on the response of blood sugar, unesterified fatty acids, insulin and growth hormone to a glucose load. The presence of increased catecholamines in both patients appeared to produce increased fasting plasma unesterified fatty acid levels, carbohydrate intolerance and an unusual plasma growth hormone response to glucose. There was no interference with the normal decrease in plasma unesterified fatty acids after glucose ingestion. The malignant tumour, but not the benign one, was associated with low plasma insulin levels.After removal of the benign tumour the fasting unesterified fatty acid levels became normal. In addition, following glucose ingestion there appeared to be a more normal plasma insulin and growth hormone response and improved glucose tolerance. After removal of the primary malignant tumour it is noteworthy that the distant metastases secreted abnormal amounts of both adrenaline and noradrenaline.     

Nutritional intervention with omega-3 fatty acids enhances tumor response to anti-neoplastic agents

Nutritional intervention with specific fatty acids depresses tumor growth and enhances tumor responsiveness to chemotherapy. Supplementation of tumors with long chained omega-3 polyunsaturated fatty acids results in enrichment of tumor phospholipid fractions with omega-3 fatty acids resulting in an altered membrane composition and function. Tumors enriched with long chained omega-3 polyunsaturated fatty acids possess membranes with increased fluidity, an elevated unsaturation index, enhanced transport capabilities that results in accumulation of selective anti-cancer agents, increased activity of selected drug activating enzymes, and alteration of signaling pathways important for cancer progression. These nutritionally induced changes in tumor fatty acid composition result in increased sensitivity to chemotherapy, especially in tumor lines that are resistant to chemotherapy and cause specific enhancement of cytotoxicity to tumor cells and protection of normal cells. Pre-disposing tumors to increased chemo-sensitivity through nutritional intervention with specific fatty acids has the potential to improve patient response to chemotherapy with fewer untoward side effects if these pre-clinical findings carry over into a clinical setting.     

An inhibin B and estrogen-secreting adrenocortical carcinoma leading to selective FSH suppression

OBJECTIVE: Hormone-secreting adrenocortical tumors are frequently associated with endocrine syndromes. We describe a 30-year-old man who had abdominal pain, a nodule in the right breast and loss of libido. Abdominal magnetic resonance imaging revealed a very large tumor in the right adrenal gland. METHODS: Hormonal profile disclosed increased levels of estradiol and slightly low testosterone levels. The basal and stimulated LH levels were normal, whereas basal and stimulated FSH levels were totally suppressed. Cortisol and adrenal androgen levels were normal. The unusual finding of selective FSH suppression suggested secretion of inhibin B by the adrenocortical tumor. A very high level of serum inhibin B (405 pg/ml) was demonstrated by ELISA assay. Right adrenalectomy and nephrectomy were performed and the tumor was classified as a malignant tumor (Weiss score: 7.0) and unilateral mastectomy disclosed a lipoma. RESULTS: One week after surgery, a GnRH-stimulation test disclosed normal basal and stimulated FSH levels and low levels of inhibin B and estradiol. Immunohistochemical analysis with anti-B-inhibin antibody revealed intense staining in the adrenocortical tumor cells. One month after surgery, an abdominal magnetic resonance imaging revealed a local recurrence of the tumor and a second surgery was performed with partial resection of the tumor and the patient died 1 year after the first surgery. CONCLUSION: We herein report the first inhibin B and estradiol-secreting adrenocortical carcinoma. The unusual selective inhibition of FSH secretion should be considered a valuable hormonal finding for the diagnosis of inhibin B-secreting adrenocortical tumors.     

Endoplasmic reticulum-located PDAT1-2 from castor bean enhances hydroxy fatty acid accumulation in transgenic plants

Ricinoleic acid (12-hydroxy-octadeca-9-enoic acid) is a major unusual fatty acid in castor oil. This hydroxy fatty acid is useful in industrial materials. This unusual fatty acid accumulates in triacylglycerol (TAG) in the seeds of the castor bean (Ricinus communis L.), even though it is synthesized in phospholipids, which indicates that the castor plant has an editing enzyme, which functions as a phospholipid:diacylglycerol acyltransferase (PDAT) that is specific to ricinoleic acid. Transgenic plants containing fatty acid Δ12-hydroxylase encoded by the castor bean FAH12 gene produce a limited amount of hydroxy fatty acid, a maximum of around 17% of TAGs present in Arabidopsis seeds, and this unusual fatty acid remains in phospholipids of cell membranes in seeds. Identification of ricinoleate-specific PDAT from castor bean and manipulation of the phospholipid editing system in transgenic plants will enhance accumulation of the hydroxy fatty acid in transgenic seeds. The castor plant has three PDAT genes; PDAT1-1 and PDAT2 are homologs of PDAT, which are commonly found in plants; however, PDAT1-2 is newly grouped as a castor bean-specific gene. PDAT1-2 is expressed in developing seeds and localized in the endoplasmic reticulum, similar to FAH12, indicating its involvement in conversion of ricinoleic acid into TAG. PDAT1-2 significantly enhances accumulation of total hydroxy fatty acid up to 25%, with a significant increase in castor-like oil, 2-OH TAG, in seeds of transgenic Arabidopsis, which is an identification of the key gene for oilseed engineering in production of unusual fatty acids.     

All fatty acids are not equal: discrimination in plant membrane lipids

Plant membrane lipids are primarily composed of 16-carbon and 18-carbon fatty acids containing up to three double bonds. By contrast, the seed oils of many plant species contain fatty acids with significantly different structures. These unusual fatty acids sometimes accumulate to >90% of the total fatty acid content in the seed triacylglycerols, but are generally excluded from the membrane lipids of the plant, including those of the seed. The reasons for their exclusion and the mechanisms by which this is achieved are not completely understood. Here we discuss recent research that has given new insights into how plants prevent the accumulation of unusual fatty acids in membrane lipids, and how strict this censorship of membrane composition is. We also describe a transgenic experiment that resulted in an excessive buildup of unusual fatty acids in cellular membranes, and clearly illustrated that the control of membrane lipid composition is essential for normal plant growth and development.     

Methoxylated fatty acids reported in Rhizobium isolates arise from chemical alterations of common fatty acids upon acid-catalyzed transesterification procedures.

We obtained from a phospholipid extract of wild-type Rhizobium leguminosarum bv. trifolii ANU843 methoxylated fatty acids that had been previously reported as constitutive unusual Rhizobium fatty acids. The use of deuterated reagents and subsequent gas-liquid chromatography-mass spectrometry analyses showed that these methoxylated fatty acid derivatives are the products of chemical alterations of common cyclopropane-containing and unsaturated fatty acids occurring during various acid-catalyzed transesterification treatments aimed at producing the methyl ester derivatives. Similar results were obtained from a phospholipid extract of Escherichia coli K-12. In contrast, these chemical alterations were not induced by an alkaline methanolysis method of transesterification. If an acidic treatment is needed to release the fatty acids from the source molecule, the finding of unusual methoxylated fatty acids should be carefully confirmed with deuterated reagents.     

Incidentally Identified Adrenal Lipoma: Case Report and Review of Related Literature

ObjectiveTo report a case of an incidentally identified adrenal lipoma in a 68-year-old man with flank pain and hypertension.MethodsThe clinical, computed tomographic, and magnetic resonance imaging findings in this patient are described, and the pathologic features of the tumor are characterized. Moreover, the related literature is reviewed and summarized.ResultsThe patient had undergone coronary artery bypass grafting, had a prosthetic heart valve, and required systemic anticoagulation. Computed tomography showed a well-circumscribed left adrenal lesion with evidence of scattered foci of macroscopic fat; these findings were confirmed on magnetic resonance imaging. After laparoscopic left adrenalectomy, pathologic examination revealed a well-circumscribed, fatty, 7-cm adrenocortical-based tumor, which weighed 135 g. Histologic sampling disclosed mature adipose tissue without evidence of myeloid heterotopy or features of malignant involvement, and adrenal lipoma was diagnosed. On the basis of our review of the English-language literature, this tumor is the 11th reported case of adrenal lipoma. The vast majority of these tumors have been asymptomatic and identified incidentally on imaging or at autopsy. A minority of patients have had a history of hypertension.ConclusionWith the increased utilization and sensitivity of abdominal imaging techniques, identification of nonfunctional adrenal tumors has become more frequent. Adrenal lipoma should be included in the differential diagnosis of lipomatous adrenal tumors. (Endocr Pract. 2008; 14:209-212)     

110例绝经后子宫出血相关因素分析

目的:探讨绝经后子宫出血的年龄、绝经年限、子宫内膜厚度与疾病的关系,以及相关因素分析。方法:回顾分析2003～2005诊治的110例自然绝经1年以上子宫再次出血者的诊刮或子宫切除的临床病理资料。结果:绝经后病理结果分别为非器质性病变44例占40%、良性病变26例占23.6%和恶性肿瘤(子宫内膜癌)40例占36.4%,相关影响因素有IUD 13例占11.8%、高血压22例占20%和肥胖17例占15.5%。结论:绝经后子宫出血的首要原因是子宫内膜非器质性病变,年龄越大、绝经年限越长、内膜越厚、恶性肿瘤发生率愈高,其中IUD、高血压、肥胖为影响因素。     

Engineering oilseeds for sustainable production of industrial and nutritional feedstocks: solving bottlenecks in fatty acid flux

Oilseeds provide a unique platform for the production of high-value fatty acids that can replace non-sustainable petroleum and oceanic sources of specialty chemicals and aquaculture feed. However, recent efforts to engineer the seeds of crop and model plant species to produce new types of fatty acids, including hydroxy and conjugated fatty acids for industrial uses and long-chain omega-3 polyunsaturated fatty acids for farmed fish feed, have met with only modest success. The collective results from these studies point to metabolic 'bottlenecks' in the engineered plant seeds that substantially limit the efficient or selective flux of unusual fatty acids between different substrate pools and ultimately into storage triacylglycerol. Evidence is emerging that diacylglycerol acyltransferase 2, which catalyzes the final step in triacylglycerol assembly, is an important contributor to the synthesis of unusual fatty acid-containing oils, and is likely to be a key target for future oilseed metabolic engineering efforts.     

Stereotactic mesencephalotomy versus multiple thalamotomies in the treatment of chronic cancer pain syndromes

Two neurosurgical centers, Bologna (Italy) and Freiburg (FRG), have compared results obtained with stereotactic mesencephalotomy (SM; Bologna) and multiple thalamotomies (MT; Freiburg) in the surgical treatment of chronic cancer pain syndromes. In total, 161 patients were operated, 109 in Bologna and 52 in Freiburg. In SM the lesions were single and centered on the spinothalamic tract at the mesencephalic level, while in MT the lesions were multiple in the thalamic nuclei (ventrocaudal parvocellular nucleus, nucleus limitans, lamella medialis, centromedian nuclei). The following results emerged after 2-7 months' follow-up: (1) in an antalgic sense, SM was much more beneficial, with 91 patients (83.5%) pain-free after the operation versus 27 patients (51.9%) who had only an attenuation of the pain syndrome after MT; (2) SM, compared to MT, is burdened by mortality and a higher morbidity [2 deaths (1.8%) vs. 0; 3 anesthesia dolorosa and 8 severe gaze palsies (10.1%) vs. only 1 case of permanent aphasia (1.9%)].