Skin biopsy for the diagnosis of peripheral neuropathy

Skin biopsy has become an accepted tool for investigating small nerve fibres, which are invisible to conventional neurophysiological tests even though they are affected early on in peripheral neuropathies of varying aetiology. Morphometric analysis of epidermal and dermal nerves has proved to be reliable, reproducible and unaffected by the severity of neuropathy, making skin biopsy useful for diagnosing small fibre neuropathy (SFN) in clinical practice. The possibility of obtaining skin biopsy specimens from different sites of the body, to repeat them within the area of the same sensory nerve, to distinguish between somatic and autonomic nerves and to investigate the expression of nerve-related proteins has widened the potential applications of this technique to clinical research. Skin biopsy performed using a minimally invasive disposable punch is a safe and painless procedure. Using specific antibodies with bright-field immunohistochemistry or immunofluorescence technique, it is possible to investigate unmyelinated fibres innervating the epidermis of hairy and glabrous skin, large myelinated fibres supplying specialized corpuscles in glabrous skin, and autonomic fibres innervating sweat glands, blood vessels and arrector pilorum muscles. This review discusses the features of skin innervation in hairy and glabrous skin, the functional properties of skin nerve fibres and their changes in peripheral neuropathies.     

Percutaneous renal biopsy as an outpatient procedure

Percutaneous renal biopsy (PRB) is a safe and effective tool in the diagnosis and management of renal disease. It is the gold standard for evaluating renal parenchymal disease. It is both useful for diagnosis and monitoring progress of renal diseases. Where facilities and personnel are available to carry out the procedure in developing countries, it has become increasingly difficult for patients to pay for hospital admission fees, the procedure, and processing of the samples obtained. Information on the success rate and safety of the procedure is of interest to nephrologists for cost-benefit considerations and medicolegal purposes. This paper reports the outcome of outpatient PRB done among patients of the University College Hospital, Ibadan, Nigeria. With the use of ultrasound guidance, PRB remains a safe procedure and can be done on an outpatient basis.     

Morphology of diabetic neuropathy

The morphological findings in peripheral nerves in diabetic subjects are reviewed. Diabetes is probably the most frequent cause of neuropathy. However it does not constitute a single nosological entity but is comprised of a variety of clinical and morphological changes. These are considered to be the consequences of metabolic derangements resulting from chronic hyperglycemia. Distal symmetrical neuropathies, which are most common, are characterized by axonal degeneration and segmental demyelination with loss of nerve fibres and fibrosis. Remyelination and axonal sprouting occur. Microvascular changes consist of thickening and hyalinization of the walls of the vessels. On electron microscopy these vessels appear thickened and show reduplication of the basal lamina that surrounds the endothelial cells and pericytes. The morphological bases of proximal symmetrical motor neuropathy, as well as of focal and multifocal neuropathies are briefly described. The synopsis of current knowledge can be helpful in diagnosis and differential diagnosis of disorders of the peripheral nervous system.     

Metastasis as a beneficial process.

The most important message to be found in the "Fourth report on end results in cancer" in the U.S., states that with the progression of cancer, its force of mortality declines. This has been reexamined in the present study. The declining force of mortality implies that as the disease advances the chances of the average patient to survive, improve. Since in the cancer patient all vital functions gradually deteriorate, and the only process gaining with time is his tumor load, one has to consider the possibility that the improving chances of the cancer patient could be linked with the amount of tumor mass in his body. These ideas are illustrated by the following example. Cancer could result from a gradual loss of a vital tissue product 'A', to be replaced by an analogous tissue product 'B' which is of embryonal origin. In the adult, 'B' is produced by stem cells which gradually adapt to the loss of the primary product and increase in number. 'B' is less efficient than 'A' to meet the necessary vital functions. Its deficiency in quality is however augmented by quantity. In order to keep up with the increasing demand, the stem cells proliferate and spread throughout the organism where each metastasis continues to secrete 'B'. The penalty inflicted by this compensatory mechanism is relatively high. Some metastases hit vital functions, and the increasing tumor load depletes the available energy sources. The net effect however is beneficial since without metastasis the organism would have succumbed to the disease in its earliest stage.     

Plasma dihydroxyphenylglycol (DHPG) as an index of diabetic autonomic neuropathy

Forearm venous plasma noradrenalin and dihydroxyphenylglycol (DHPG) concentrations were measured in eight diabetic patients with and eight diabetic patients without neuropathy. Plasma noradrenalin was on average the same in patients with and without neuropathy and correlated to serum creatinine. Plasma DHPG concentrations were significantly reduced in patients with autonomic neuropathy as compared to patients without neuropathy (P less than 0.05). A low plasma DHPG/noradrenalin ratio in forearm venous blood identified all patients with autonomic neuropathy except one (P less than 0.02). Measuring the plasma DHPG/noradrenalin ratio may circumvent the problem of unrepresentative noradrenalin release from the forearm.     

Recommended procedure for histopathologic processing of lymph node biopsy

A standard procedure of sampling, transportation, fixation and further processing for microscopical investigation of lymph node biopsies is presented. It points out the importance of a perfectly stained survey section and well done immunohistochemical reactions as well as of sense of the second opinion for precise histopathological diagnosis.     

Skin biopsy findings: implications for the pathophysiology of fibromyalgia

The mechanisms responsible for symptom expression in fibromyalgia (FM) are complex. The most consistently detected objective abnormalities in FM involve pain-processing systems. Up to recently, central nervous system was a primary focus of investigations in FM. Although it is unlikely that FM occurs because of primary disorders of the peripheral tissues, there are still data to suggest that some abnormalities can be detected in the periphery. With the recognition of abnormalities in skin of some FM patients, it is now apparent that the role of peripheral nerve endings in FM is much greater than previously thought. The aim of this paper is to review literature concerning the skin biopsy findings of FM patients and discuss their potential relevance to FM. This paper suggests that patients with FM represent a state of the dysfunction of descending, antinociceptive pathways and low hypothalamic-pituitary-adrenal function. This state is further proposed to result in many skin biopsy findings associated with the disorder, including increased N-methyl-d-aspartate receptors subtype 2D expression, neurogenic inflammation and characteristic electron microscopic findings. Future direction of research would be identification of specific laboratory markers such as skin biopsy for diagnostic and clinical evaluation purposes in FM.     

Regeneration and repair of myelinated fibers in sural-nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil

There is reason to believe that diabetic neuropathy may be related to the accumulation of sorbitol in nerve tissue through an aldose reductase pathway from glucose. Short-term treatment with aldose reductase inhibitors improves nerve conduction in subjects with diabetes, but the effects of long-term treatment on the neuropathologic changes of diabetic neuropathy are unknown. To determine whether more prolonged aldose reductase inhibition reverses the underlying lesions that accompany symptomatic diabetic peripheral polyneuropathy, we performed a randomized, placebo-controlled, double-blind trial of the investigational aldose reductase inhibitor sorbinil (250 mg per day). Sural-nerve biopsy specimens obtained at base line and after one year from 16 diabetic patients with neuropathy were analyzed morphometrically in detail and compared with selected electrophysiologic and clinical indexes. In contrast to patients who received placebo, the 10 sorbinil-treated patients had a decrease of 41.8 +/- 8.0 percent in nerve sorbitol content (P less than 0.01) and a 3.8-fold increase in the percentage of regenerating myelinated nerve fibers (P less than 0.001), reflected by a 33 percent increase in the number of myelinated fibers per unit of cross-sectional area of nerve (P = 0.04). They also had quantitative improvement in terms of the degree of paranodal demyelination, segmental demyelination, and myelin wrinkling. The increase in the number of fibers was accompanied by electrophysiologic and clinical evidence of improved nerve function. We conclude that sorbinil, as a metabolic intervention targeted against a specific biochemical consequence of hyperglycemia, can improve the neuropathologic lesions of diabetic neuropathy.     

Potential beneficial role of sevelamer hydrochloride in diabetic retinopathy

Patients with chronic kidney disease (CKD) experience co-morbid illnesses, including cardiovascular disease and retinopathy. Sevelamer hydrochloride (Renagel®); a non-calcium phosphate binder reduces coronary artery and aortic calcification as compared to calcium containing phosphate binders and additionally effects inflammatory biomarkers such as C-reactive protein (CRP), and lowers LDL cholesterol in patients with CKD. Since retinopathy is proven to be associated with increased coronary calcification, shared pathophysiological processes may contribute to both microvascular and macrovascular disease. We here suggest three different mechanisms of possible sevelamer’s influence on the retinopathy: (1) by direct effect on the microvasculature through lowering CRP and LDL, involved in endothelial dysfunction and atherogenesis, (2) indirectly by attenuation of vascular calcification of aorta and carotid internal artery, it reduces ischaemia and improves circulation in the opthalmic artery and hence postponing retinopathy, (3) through hypertension by reducing atherosclerosis and calcification of carotid arteries, sevelamer decreases stiffness and intima-media wall thickness, therefore lowering blood pressure, which is well known to increase progression of diabetic retinopathy. So far no studies have yet been published on the direct influence of sevelamer on the retinopathy which we believe has good theoretical background. With its combined macrovascular and microvascular effect, sevelamer could potentially postpone and/or decrease retinopathy in diabetic patients with hypertension, and that are on hemodialysis or even predialysis patients.     

Histopathologic evaluation of liver biopsy for cirrhosis

In current medical practice, the clinical diagnosis of cirrhosis is rendered when a patient has suggestive imaging findings or features of portal hypertension (pHTN). Liver biopsy may be considered to assess potential underlying cause(s). Cirrhosis, however, is not the only etiology of pHTN; in fact, schistosomiasis remains a significant factor worldwide. pHTN results from obstruction of hepatic blood flow; it is classified clinically based on either the anatomic location of obstruction or hepatic venous pressure gradient measurements. The clinical categories carry clinicopathologic significances. Histopathologically, pHTN is manifest with either cirrhotic or noncirrhotic features. Noncirrhotic pHTN results from a heterogeneous group of disease processes, all of which result in vascular remodeling with variable parenchymal nodularity and fibrosis. This review summarizes liver biopsy findings of cirrhosis and possible etiologies and provides a stepwise approach for the histologic differential diagnosis of a liver biopsy done for "cirrhosis."     

The lung as a privileged site for the beneficial actions of PGE2

Prostaglandin E2 (PGE2) is commonly considered a potent proinflammatory mediator and is involved in several inflammatory diseases. In the lung, as opposed to many other parts of the body, PGE2 has a role in limiting the immune-inflammatory response as well as tissue repair processes. Understanding the full implications of the regulatory role of PGE2 and how beneficial processes, such as inflammation and tissue repair, become dysregulated to the point of causing disease, might disclose new perspectives in the treatment of pulmonary diseases.     

阴道镜下多点活检联合LEEP术诊治宫颈上皮内瘤变的临床效果

目的探讨阴道镜下多点活检联合LEEP术在宫颈上皮内瘤样变(CIN)诊治中的应用价值。方法 60例经阴道镜下多点活检病理诊断为CINⅡ～Ⅲ级患者,应用LEEP术诊治,比较阴道镜下多点活检病理结果与LEEP术后病理结果,观察治愈率和术后并发症发生情况。结果经阴道镜下多点活检病理证实的60例CINⅡ～Ⅲ级患者,LEEP术后经病理诊断相符42例,诊断符合率为70.0%。29例CINⅡ级经LEEP术后病理诊断符合率为79.3%(29/60),31例CINⅢ级经LEEP术后病理诊断符合率为61.3%(31/60);LEEP术后治愈率为93.3%,复发率为1.7%,术后并发症发生率为3.3%。结论阴道镜下多点活检联合LEEP术诊治CINⅡ～Ⅲ级可以提高诊断率,降低误诊率;且LEEP术治疗CINⅡ～Ⅲ级治愈率高,复发率和术后并发症低。     

Recommendations for the biopsy procedure and assessment of skeletal muscle biopsies

 Muscle biopsy has a valuable diagnostic role in many neuromuscular diseases, but it is an invasive investigation that should not be undertaken lightly. Furthermore, the biopsy procedure and subsequent laboratory processing of the specimen may significantly influence the results. The following guide is designed to optimise the diagnostic information that can be obtained from muscle biopsy. It covers the whole procedure, from selection of the biopsy site and technique of biopsy, progressing through freezing of the specimen for histochemistry, and the role of immunocytochemistry and electron microscopy. Finally, the contents of a model biopsy report are considered. Received: 7 April 1997 / Accepted: 7 April 1997