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PubMed2000

Lipodystrophy syndrome in HIV infection: what is it, what causes it and how can it be managed?

Since the introduction of HIV-1 protease inhibitors as components of antiretroviral drug combination regimens, the clinical course of HIV disease and opportunistic infections has changed dramatically. Besides the favourable virological, immunological and clinical impact of highly active antiretroviral therapy (HAART), several adverse drug reactions have been observed in patients with HIV receiving therapy. Particularly, peripheral lipodystrophy, central adiposity, dyslipidaemia and insulin resistance have been described with a prevalence of up to 80% in patients infected with HIV, and attributed to almost all components of HAART. Hyperlipidaemia is characterised by an increase of low and very low density lipoprotein-cholesterol as well as apolipoproteins B and E. Several studies strongly suggest that there are either multiple syndromes or a variety of factors inducing different changes that influence the ultimate phenotype. Similarities between HIV-associated fat redistribution and metabolic abnormalities with both inherited lipodystrophies and benign symmetric lipomatosis suggest the pathophysiological involvement of, for example, nuclear factors like lamin A/C and drug-induced mitochondrial dysfunction. Moreover, there is some evidence that cytokines and hormones impair fat and glucose homeostasis in patients with HIV receiving HAART. Three years after the first description of HIV therapy-associated abnormal fat redistribution, there is still an ongoing discussion about the case definition, diagnostic procedure and treatment options for both body shape changes and metabolic disturbances. Regarding therapy, there is a major concern about possible complex pharmacological interactions and overlapping adverse effects between HAART and, for example, lipid-lowering therapy. In addition, the likely contribution of both nucleoside analogue reverse transcriptase inhibitors and protease inhibitors to the development of abnormal fat redistribution in patients with HIV limits options of changing to alternative effective antiretroviral drug combinations. Thus, the occurrence of hyperlipidaemia, maturity onset diabetes mellitus, and marked changes in body habitus resulted in important social and clinical consequences such as an increased risk of atherosclerosis. It also sheds new light on the use of protease inhibitors regarding risk factors for the initial treatment decision. In this article, we discuss the features, pathogenesis and treatment options for body fat redistribution and metabolic disturbances associated with HAART in HIV-1 infection.

Animals↗

PubMed1981

The apical cap.

Apical caps, either unilateral or bilateral, are a common feature of advancing age and are usually the result of subpleural scarring unassociated with other diseases. Pancoast (superior sulcus) tumors are a well recognized cause of unilateral asymmetric apical density. Other lesions arising in the lung, pleura, or extrapleural space may produce unilateral or bilateral apical caps. These include: (1) inflammatory: tuberculosis and extrapleural abscesses extending from the neck; (2) post radiation fibrosis after mantle therapy for Hodgkin disease or supraclavicular radiation in the treatment of breast carcinoma; (3) neoplasm: lymphoma extending from the neck or mediastinum, superior sulcus bronchogenic carcinoma, and metastases; (4) traumatic: extrapleural dissection of blood from a ruptured aorta, fractures of the ribs or spine, or hemorrhage due to subclavian line placement; (5) vascular: coarctation of the aorta with dilated collaterals over the apex, fistula between the subclavian artery and vein; and (6) miscellaneous: mediastinal lipomatosis with subcostal fat extending over the apices.

Adult↗

PubMed1993

Extrapleural fat collections: pseudotumors and other confusing manifestations.

Because thoracic fat is mobile and plastic, it can assume a variety of shapes and distributions. Fat collections can be confusing, and some can even mimic tumors. This essay highlights the variable and potentially confusing manifestations of normal thoracic fat on plain radiographs and CT scans. It does not emphasize fatty tumors, ordinary mediastinal lipomatosis, costal fat pads, or diaphragmatic hernias, as these topics have been reviewed recently.

Adipose Tissue↗

PubMed1997

CT appearance of lipomatous hypertrophy of the interatrial septum.

OBJECTIVE: We undertook this study to determine the CT findings of lipomatous hypertrophy of the interatrial septum, an asymptomatic and underrecognized benign proliferation of fat within the atrial septum. MATERIALS AND METHODS: We retrospectively identified 12 cases of lipomatous hypertrophy of the interatrial septum by searching the radiology records at our institution from 1991 to 1995. We reviewed the CT scans of these patients to determine the distribution and morphology of fat within the interatrial septum. RESULTS: In all patients with lipomatous hypertrophy, a mass of fat attenuation extended from the coronary sinus to just above the level of the aortic root with relative sparing of the fossa ovalis, which resulted in a dumbbell configuration. Average dimensions were 7 cm for craniocaudal extent (range, 6-9 cm), 4.5 cm along the interatrial septum (range, 3.6-6.2 cm), and 2.7 cm perpendicular to the septum (range, 1.5-4.8 cm). Increased epicardial fat was seen on CT scans in 10 patients (83%). CT revealed mediastinal lipomatosis in six patients (50%). No patients had undergone corticosteroid treatment or total parenteral nutrition. No electrocardiographic or functional cardiac abnormalities were seen. CONCLUSION: On standard, high-resolution, and enhanced CT images, lipomatous hypertrophy of the interatrial septum is shown as a nonenhancing smoothly marginated homogeneous dumbbell-shaped mass of fat attenuation confined to the interatrial septum. These characteristic morphologic features allow confident diagnosis and help differentiate this benign condition from other cardiac masses.

Adipose Tissue↗

PubMed2006

[Influence of the myocardial bridging phenomenon on the myocardial structure and the coronary arteries wall structure changes].

BACKGROUND/AIM: Our research was performed to evaluate the influences of the myocardial bridgings of coronary arteries on the myocardial and coronary arteries wall structure chages, that could be a reason for multiple heart malfunctions. METHODS: We analyzed the autopsy material, collected during a five-years period, and especially the group of 575 cases with the major aim to diagnose mors naturalis. In all cases with the presence of myocardial bridge over the arterial coronary wall revealed at autopsy, samples were taken for microscopic verification and examination. RESULTS: We found myocardial bridges over the coronary arteries or their major branches in 27 of the cases (4.70%). We believe that myocardial bridges compromise coronary perfusion by cyclic compression of the overbridged vessels, and that it could be the initial factor in the pathogenesis of arteriosclerotic degeneration processes on the coronary artery wall. We found different grades of arteriosclerotic changes in 88.89% of the cases, as well as fibrosis of myocardium in 88.89% and lipomatosis in 66.67% of the cases with the present myocardial bridges. CONCLUSION: Our results suggested that myocardial bridging of coronary arteries and/or their branches was the pathological and even lethal phenomenon that de serves more intensive clinical evaluation.

Adult↗

PubMed1986

An immunohistochemical, ultrastructural, and physiologic study of pancreatic islets from copper-deficient, penicillamine-treated rats.

Murine copper deficiency induced by diet and supplemented with a copper chelator is known to produce a progressive atrophy of pancreatic acinar tissue largely replaced by noninflammatory lipomatosis, while the ductal and endocrine systems appear to remain unaffected. The islets were studied morphologically and physiologically in animals rendered copper deficient by diet and supplemented with D-penicillamine. Using immunohistochemistry, the distribution of islet cell types from copper-deficient animals exhibited a normal cellular complement for A-, B-, D-, and PP-cells. Ultrastructural analysis showed the islet tissue remains normal in appearance during the course of the metal-deficient state. Physiologic data based on the response of islets to a low- and high-glucose load in perfused, isolated pancreata as well as intravenous glucose tolerance tests indicated that insulin-secreting B-cells were functionally normal. Because of the accessibility of islets enhanced by atrophy of acini, this model may be adopted for the isolation of viable islets and for in situ physiologic studies of islet hormone secretion.

Animals↗

PubMed2002

Placental transmogrification of the lung is a histologic pattern frequently associated with pulmonary fibrochondromatous hamartoma.

CONTEXT: Placental transmogrification of the lung is a term introduced to describe a peculiar histologic pattern characterized by formation of placental villuslike structures in the lung parenchyma. It has been reported to occur in association with bullous emphysema and lipomatosis. OBJECTIVES: To study the relationship between placental transmogrification and pulmonary hamartomas. DESIGN AND METHODS: Reports of 38 cases of pulmonary hamartomas during 18 years (1982-1999) were reviewed. All histologic slides of these cases were examined for the presence of villuslike papillary projections and placenta-like structures. Hamartomas with prominent papillary projections or placenta-like structures were further investigated to assess the histogenesis and proliferation of epithelial and stromal cells. Immunohistochemical analysis was performed on paraffin-embedded tissue using monoclonal antibodies against Ki-67 and thyroid transcription factor 1 (TTF-1) and polyclonal antibodies against c-Kit antigen (a stem cell factor receptor/mast cell growth factor receptor) in conjunction with Leder stain for naphthol-ASD-chloroacetate esterase. RESULTS: Placental transmogrification was identified in 6 of 38 cases of pulmonary fibrochondromatous hamartomas. The histologic change consisted of an abundant myxoid or edematous fibroadipose stroma with a respiratory epithelial lining, resulting in papillary projections that resembled immature placental villi. Epithelium lining the papillary projections was positive for TTF-1 (70%-90%) and Ki-67 (3%-5%). In contrast, stromal cells were negative for TTF-1 with only rare cells immunoreactive for Ki-67. A number of stromal spindle cells and occasional cells in epithelium were c-Kit immunoreactive; however, concurrent Leder stain demonstrated that these c-Kit-positive cells were mast cells and not stem cells. CONCLUSIONS: Placental transmogrification is frequently associated with pulmonary fibrochondromatous hamartomas and may be induced by or associated with a proliferation of lining epithelial components in the hamartomas. The significance of numerous mast cells within stroma of placental transmogrification is unclear and their possible role in inducing stromal proliferation needs to be further evaluated.

Aged↗

PubMed1976

[Insufficiency of secretion from the exocrine pancreas in infants (excluding mucoviscidosis) Diagnosis and consequences].

The diagnosis of insufficiency of exocrine pancreatic secretion was made in two infants after demonstration of a marked decrease in the flow rate of enzyme secretions during the duodenal infusion of milk and after the IV injection of C.C.K.-P.Z. The two infants had a normal sweat test. One had pancreatic lipomatosis with neuropaenia, whilst the other had pancreatic deficiency which did not fall into the context of Shwachman's syndrome. This study suggests that the absence of exocrine pancreatic secretion is accompanied by multiple abnormalitites : decreased absorption of fats and vitamin B12 and, it would appear, variations in certain activities of the jejunal mucosa and decreased insulin stimulation from the intestine. Such a situation reflects the complexity of the relations established between the organs participating in the processes of absorption and digestion.

Child↗

PubMed1999

[Cystitis glandularis].

OBJECTIVE: To discuss the presenting features, diagnosis and treatment of cystitis glandularis. METHODS/RESULTS: 15 patients consulted for voiding syndrome, hematuria, hypogastric pain and chronic cystitis. Ten patients were evaluated by IVP which showed bilateral ectasia in 6, an abnormal renal pelvis in one and the remaining three patients were normal. Eight patients were evaluated by cystography which showed a reduced bladder capacity in three, bilateral reflux in three and an abnormal bladder wall in two patients. Urinalysis was performed in all 15 patients; only 5 patients showed a positive culture. These 5 patients had recurrent episodes and underwent cystoscopy and biopsy and/or TUR. Sixty percent was associated with a foreign body, lithiasis, bladder exstrophy, pelvic lipomatosis and BPH. Diagnosis was based on the histological findings; 40% had a bladder tumor. CONCLUSIONS: Patients with cystitis glandularis present with voiding syndrome and chronic cystitis. The IVP, US and cystographic findings are usually normal or may indicate a tumor. Diagnosis is based on the histological findings.

Cystitis↗

PubMed1999

The role of PTEN, a phosphatase gene, in inherited and sporadic nonmedullary thyroid tumors.

PTEN/MMACI/TEP1, a tumor suppressor gene located on 10q23.3, encodes an almost ubiquitously expressed dual-specificity phosphatase. Germline mutations in PTEN have been found in the majority of cases of sporadic and familial Cowden syndrome (CS), an autosomal dominant inherited cancer syndrome characterised by multiple hamartomas and benign and malignant disease of the thyroid and breast. Interestingly, germline mutations in PTEN have also been found in about 50% of a related but distinct disorder, Bannayan-Ruvalcaba-Riley syndrome (BRR), which is characterised by neonatal-onset macrocephaly, mental retardation, Hashimoto's thyroiditis, lipomatosis, haemangiomas, hamartomatous polyps, and pigmented macules of the glans penis. Somatic PTEN mutation has been described to a greater or lesser extent in various benign and malignant tumor types. Somatic deletions have been described in follicular adenomas of the thyroid and papillary thyroid carcinomas.

Genes, Tumor Suppressor↗

PubMed1976

[Experimental investigations of muscle transplants in correction of congenital diaphragmatic defects (author's transl)].

Rives muscle plasty using a pediculate flap of the latissimus dorsi muscle is an approved method for correction of large congenital diaphragmatic defects. To study morphology and function of the transplanted muscle flap 10 beagle dogs were operated upon bilaterally in two stages. Thus a total of 20 muscle transplants was evaluated. A standard Rives plasty was performed, emg electrodes were inserted into the diaphragm as well as into the muscle transplant. The surgical procedure was tolerated very well, there was no operative mortality. The period of observation varied between 18 and 48 weeks, the average being 30 weeks. Postoperatively there was no electric activity found in the muscle transplants, whereas the diaphragm showed its characteristic interference pattern during inspiration. In 5 cases, however, action potentials appeared in the muscle flap after 12 to 16 weeks. They had the semblance of fibrillation potentials and short sharp waves and were considered to be preceding reinnervation potentials, which occured 24 to 32 weeks postoperatively in these cases. In 2 cases the emg findings were inconstant, in the residual 13 cases there was no electrical activity in the muscle transplant during all the observation time. The emg findings corresponded to the histological postmortem findings. These showed in altogether 6 cases numerous intact muscle fibres as well as nerve trunks with neurites, especially in the neighbourhood of the diaphragm. In the middle of the flap and even more near the thoracic wall the number of intact muscle fibres decreased. Thus a partial reinnervation due to muscular neurotization starting from the diaphragmatic margin was assumed in these cases. In the rest of the flaps the muscles were largely atrophic and showed considerable lipomatosis, only minor fibrosis and never a distinct scar formation. Therefore, the flaps represented living tissue with intact vascularization and functionally good adaptability. Reinnervation, observed in some cases, is not the main factor for the good clinical results obtained with Rives muscle plasty, but can improve adaptability and elasticity of the transplant considerably. According to the lack of scar formation and the preponderance of fatty tissue an increase of the transplant considerably. According to the lack of scar formation and the preponderance of fatty tissue an increase of the transplants size during growth seems possible. Thus Rives muscle plasty using a flap of the latissimus dorsi muscle to cover large congenital diaphragmatic defects seems morphologically as well as functionally superior to other procedures especially those using plastic material.

Animals↗

PubMed2000

Cutaneous side effects induced by indinavir.

HIV-protease inhibitors demonstrated such high efficacy in short-term studies that they have been approved by the FDA, even though possible toxicity still needs further investigation. In the period between January 1997 and August 1998, 101 patients, staying at San Patrignano Medical Centre (Italy), received an HIV protease inhibitor (indinavir) plus two nucleoside reverse transcriptase inhibitors (NRTI's) selected from the following: AZT, didanosine, zalcitabine, lamivudine or stavudine. Seventy-three patients were male, 28 female and their ages ranged from 25 to 60 years, with an average of 34. At the end of the study, 84 patients were suitable for evaluation, as the other 17 dropped out for various reasons. Forty-eight patients (57.1%) developed cheilitis, 34 (40.5%) experienced diffuse cutaneous dryness and pruritus, 10 (11.9%) developed asteatotic dermatitis on the trunk, arms and thighs and another 10 (11.9%) complained of scalp defluvium. A severe alopecia was observed in only 1 patient (1.2%), while 6 reported that their body hair had become fairer, thinner and shed considerably. Multiple pyogenic granulomas were observed in the toenails of 5 patients (5. 9%). Softening of the nail plate was noted in 5 subjects as well. A peripheral lipodystrophy syndrome was noted in 12 patients (14.3%). Among these, one patient only developed a "buffalo hump" and another had diffused lipomatosis. The temporal relationship between the taking of indinavir and the onset of such cutaneous effects was striking. This was confirmed by the regression of symptoms in those patients who later discontinued indinavir. The emerging side effects of protease inhibitors require a multidisciplinary team for adequate diagnosis and treatment. Cutaneous toxicity involving the patient's own body image has a peculiar influence on compliance to the treatment and the patient's quality of life.

Adult↗

PubMed2000

Reversal of cachexia in patients treated with potent antiretroviral therapy.

The introduction of HAART has changed the nutritional status of HIV patients. In the pre-protease inhibitor (PI) era, more than 60% of HIV-positive persons presented with protein energy malnutrition (PEM) and vitamin and mineral deficit. This caused progressive physical-metabolic wasting (wasting syndrome/cachexia) and increased susceptibility to opportunistic infections and drug toxicity. PEM was a concurrent cause in 80% of deaths attributed to AIDS. Since 1996, the year in which PIs were introduced, the number of patients dying as a result of AIDS has decreased by two thirds, and cachexia is no longer the AIDS terminal phase in developed countries. But different patterns of nutritional status changes have appeared in association with the use of newer anti-HIV therapies and with longer survival of HIV-infected patients. A new clinical and laboratory syndrome--lipodystrophy syndrome--now affects patients receiving PI-based therapy. This syndrome consists of changes in body shape that are caused by an abnormal redistribution of fat. Fat accumulates in the abdominal area (truncal and visceral obesity), in the axillary pads (bilateral symmetric lipomatosis), and in the dorsocervical pads ("buffalo hump," "bull neck") but decreases in the legs, arms, and nasolabial and cheek pads (peripheral lipodystrophy). Hyperlipidemia and insulin resistance are also frequently present (metabolic syndrome X). Pathogenic mechanisms of lipid and fat tissue disturbances are discussed in this article, and the clinical approach to patient management and therapeutic options for lipodystrophy and lipid dysmetabolism is evaluated.

Acquired Immunodeficiency Syndrome↗

PubMed2000

[Neurological complications of renal transplant].

Advances in surgical procedures and new immunosuppressor therapies have improved the outcome of renal grafts. However, these changes have been accompanied by infectious, neoplastic and neurologic complications. The purpose of this study was to determine the incidence of neurologic complications among 542 patients receiving a renal transplant (from living or cadaveric donors) at CEMIC between 1970 and 1996. Neurologic complications occurred in 43 patients (8%) as follows: 8 meningitis (1.5%), 8 acute confusional syndrome (1.5%), 7 encephalitis (1.3%), 7 cerebrovascular accidents (1.3%), 6 convulsions (1.1%), 3 tumors (0.5%), 3 femoral nerve lesion (0.5%), and 1 epidural lipomatosis (0.1%). Etiologic agents most commonly observed in meningitis were: Cryptococcus neoformans, Listeria monocytogenes and Mycobacterium tuberculosis. Major difficulties arose in the diagnosis of encephalitis. Diagnosis of the above complications required clinical astuteness and repeated bacteriologic, serologic and imaging studies.

Adolescent↗

PubMed2000

New dysostosis showing multilevel absence of vertebral pedicles: unique developmental anomaly of vertebral arches?

We report on an apparently normal child who shows hypopaplasia of the vertebral pedicles and posterior arches of several cervical, thoracic, and lumbar vertebrae with normally fused spinous apophyses, hypoplastic sacrum, lumbar epidural lipomatosis, synostoses of some cervical vertebral disks, and sacral spina bifida. The most likely mechanism is an abnormal differentiation of the spinal processes, due most probably to an absence of differentiation in cartilage of the dense mesenchyme forming their most anterior part. Because the anomalies affect multiple levels, we highly suspect a genetic basis to this unusual dysostosis affecting the development of the posterior sclerotomes.

Adult↗

PubMed2000

[Clinical significance of magnetic resonance imaging of skeletal muscles in idiopathic inflammatory myopathies of adults].

The purpose of this study was to evaluate the clinical significance of magnetic resonance imaging (MRI) of skeletal muscles in Japanese patients with idiopathic inflammatory myopathies (IIM). MRI was performed in 23 adult patients with IIM, including 10 with polymyositis, 12 with dermatomyositis, and 1 with focal myositis. Seven (73%) of 11 patients with active IIM and 2 (17%) of 12 patients with inactive IIM showed hyperintensity of T 2-weighted images and normal intensity of T 1-weighted images, indicating "edema-like abnormalities" (MRI findings for active myositis). Muscle lipomatosis and fibrosis were demonstrated in four patients and 1 patient, respectively. Considerable selectivity of muscles in developing inflammatory disorders was found. In quadriceps muscles, for example, vastus muscles seemed to be more often affected in DM patients, whereas adductors were more often affected in PM patients. Serial examination of muscle MRIs was carried out in 4 patients and the findings paralleled the disease activities. The muscle MRI findings did not necessarily correlate with other findings, such as the presence of muscle weakness, elevated serum creatine kinase levels, myogenic electromyogram, or muscle biopsy findings. The muscle MRI was considered to be an additional useful tool for the diagnosis, evaluation of disease activity, and planning treatment of IIM.

Adult↗

PubMed2000

[Gastric tumors with fatty components. CT findings and differential diagnosis].

PURPOSE: To assess the role of CT in diagnosing and characterizing gastric fatty tumors. MATERIAL AND METHODS: We reviewed the CT scans of 16 patients (8 men, 8 women, mean age 52 years) with gastric fatty tumors (11 lipomas, 3 liposarcomas, 1 angiolipoma, 1 teratoma) examined from 1990 to 1999. The differential diagnosis considered primary and secondary lipomatosis, carcinoma engulfing the perivisceral fat and thus mimicking a liposarcoma, mesenchymal gastric and primary peritoneal tumors. RESULTS: Lipomas involved the fundus (7/11), the body (3/11), the antrum (1/11). Multifocality was found in one case. Lesions size ranged 25 to 65 mm (mean 35 mm). All the lipomas showed homogeneous structure with negative (-30 -100) HU values. A pseudocapsule was demonstrated in 7/11 cases. No infiltrative growth was demonstrated. The angiolipoma located in the fundus showed a vascular component with strong contrast enhancement. All the liposarcomas were bigger than 10 cm and there was a strong correlation between pathologic specimen and CT findings. The differentiated liposarcomas showed the classic heterogeneous fatty density; on the contrary the myxoid and the pleomorphic types showed an aspecific structure with necrotic/cystic changes, mostly demonstrated in the myxoid type. The teratoma was a solid mass with fatty, solid, necrotic and calcified components. CONCLUSION: CT allows the diagnosis and characterization of gastric fatty tumors. The preoperative diagnosis of lipomas plays a major clinical role because it often makes surgery unnecessary.

Adult↗

PubMed2000

Neoplasms of the central nervous system of lipoid origin.

In general tumours of lipoid origin are benign. A high proportion of cases are mesenchymal neoplasms localised in subcutaneous tissue. Neurological signs related to compression of neural structures by fat within the vertebral canal were first presented in 1975. The lipogenic neoplasms represent 1-4% of spinal tumours, and generally are associated with congenital disorders of the spine. These fatty swellings are usually benign, but penetrating deeply into the spine, and connecting with spinal cord, cauda equina or filium terminale, they produce deficits. The deficits may be present at birth but they may also occur in the middle age. These events are classified as epidural lipomatosis (mostly observed in patients on chronic steroid treatment) or as lipoma, common in spinal disraphism. Intracranial tumours of lipoid origin are very rare (0.06-0.5% of brain tumours), and are probably congenital. They occur anywhere within the cranium, however a high proportion of cases tend to be located around the midline, and approximately 50% of tumours are found in the corpus callosum. Usually they are asymptomatic, and when the symptoms occur, they are frequently a result of general clinical condition. The authors present three cases of lipomatous tumours; one intracranial and two of spinal location.

Adult↗