Polyneuropathy with endoneurial immune complex deposition as the first manifestation of systemic lupus erythematosus.

A 72-year-old male presented with progressive sensorimotor polyneuropathy. Later weight loss, proteinuria and deteriorating renal function were noted. The electrophysiological examinations revealed extensive, symmetrical demyelinating and axonal polyneuropathy. Frozen sections obtained from sural nerve biopsy sample showed the presence of immune complexes and complements in the walls of the epi- and endoneurial blood vessels, and perineurium suggestive of systemic lupus erythematous (SLE). IgG and Clq deposits were also present along the basement membranes of Schwann cells. The electron microscopy confirmed the presence of immune complex deposition. Diagnosis of SLE was proven by positive serology (anti-nuclear antibodies, anti-Sm, anti-RNP, anti-double-stranded DNA) and renal biopsy showing membranous lupus nephritis with extensive immune complex deposition in the tubular basement membranes. Despite combined immunosuppressive treatment for 10 months, the patient died of complications of generalized immune complex vasculitis. The manifestation of SLE in elderly patients, especially in males, is very rare. Moreover, the polyneuropathy is an unusual initial symptom of SLE. Immune complex deposition in Schwann cell basement membrane probably plays an important role in the pathomechanism of sensorimotor polyneuropathy in SLE.

Detection of cutaneous Leishmania infection in paraffin-embedded skin biopsies using the polymerase chain reaction.

In this study the polymerase chain reaction (PCR) with previously developed oligonucleotide primers was used to detect Leishmania aethiopica in paraffin-embedded skin biopsy specimens. The Leishmania-specific 120 base pair fragment of the kinetoplast deoxyribonucleic acid (kDNA) minicircles has been amplified from all parasitologically or histologically confirmed cases of cutaneous leishmaniasis (CL), as demonstrated by gel electrophoresis and hybridization with L. aethiopica kDNA. Control specimens from patients with skin diseases other than CL were all negative. Using PCR, Leishmania were demonstrated in the skin lesions of 7 cases in a group of 40 patients in whom the parasites could not be demonstrated by histopathology or culture in vitro although lesions were clinically suggestive of CL. These data indicate that PCR, carried out on DNA extracted from formalin-fixed and paraffin-embedded tissue specimens, is a valuable method for the diagnosis of CL, especially in chronic cases where the parasite load in the lesion is low.

Aminosidine and its combination with sodium stibogluconate in the treatment of diffuse cutaneous leishmaniasis caused by Leishmania aethiopica.

Treatment of diffuse cutaneous leishmaniasis (DCL) caused by Leishmania aethiopica remains unsatisfactory as the parasite is relatively insensitive to antimonial compounds. Reports of the clinical effectiveness of aminosidine sulphate, especially in combination with sodium stibogluconate, in visceral leishmaniasis and the finding that this antibiotic is potent against L. aethiopica in vitro, prompted us to evaluate its usefulness in DCL. Two patients with long-standing, active DCL were treated for 60 d with aminosidine sulphate, 14 mg/kg/d parenterally. The skin lesions resolved completely in both patients although they relapsed subsequently. Synergism between aminosidine and stibogluconate was demonstrated in vitro against parasites isolated from the patients. This led us to administer combined therapy, aminosidine sulphate 14 mg/kg/d and sodium stibogluconate 10 mg/kg/d, to the 2 patients in relapse and to another, third patient. Treatment was continued for 2 months beyond parasitological cure. Side effects were minimal. Following treatment, a return of specific cell-mediated immunity occurred, as expressed by a moderate infiltration of lymphocytes into the lesions and by lymphocyte proliferation in vitro in the presence of live Leishmania antigen, with synthesis of interleukin-2 and interferon gamma with one patient and interleukin 4 with the other. During follow-up periods of 2 to 21 months after treatment, no sign of relapse was seen.

Histological methods for assessing myelin sheaths and axons in human nerve trunks.

Although there are many histological techniques for assessing myelin sheaths and axons in paraffin embedded or frozen sections of the peripheral nervous system, modern approaches usually use plastic embedded material. Although plastic embedding is superior for small cutaneous branches, this method has limited value for histological assessment of nerve trunks. We report three methods which together yield a comprehensive approach for thorough and detailed investigation of human nerve trunks. The rapid osmication method permitted assessment of myelinated nerve fibers from frozen sections at operation, thus providing the surgeon with guidance on the extent of nerve resection. The modification presented here resulted in permanent slides, allowing comparison of results with those of the other two procedures. The new osmium-hematoxylin technique could be performed on paraffin embedded nerves. Paraffin, unlike plastic, permitted the study of the whole cross sectional area of the nerve in single sections. Moreover, the sharp image of the myelin permitted computerized morphometry. The significantly modified axonal silver impregnation technique was performed on frozen sections mounted on glass slides, as opposed to the time-consuming impregnation of free-floating sections. The latter technique had a high success rate and permitted semiquantitative assessment of axons in nerve trunks. These methods can be performed in any routine histology laboratory and resulted in greater accuracy compared to conventional methods.

Regeneration at the predilective damage sites of nerve trunks in treated leprosy.

Superficially located large and medium sized mixed peripheral limb nerves in active leprosy have previously been shown to have well-recognized fusiform swellings. It is generally agreed that these are the sites of predilective nerve involvement where the severest degeneration and fibrosis occur. A semiquantitative histopathological study on one of these sites, the flexor retinaculum region of the posterior tibial nerve, has been carried out on 14 treated leprosy patients who suffered from total sensory loss to the foot for between 2 and 40 years. The following observations were made: (1) large-scale nerve regeneration was present as characterized by numerous Schwann cells and unmyelinated axons which formed regeneration clusters; (2) thick myelinated axons were either absent or present only in very low numbers; (3) the intraneural fibrosis was usually not severe; (4) the presence of active inflammation probably interfered with nerve regeneration; (5) it appeared that this regeneration started shortly after the onset of therapy and persisted for decades; (6) lepromatous cases were characterized by evenly distributed pathology, whereas borderline tuberculoid cases had an unevenly distributed pathology; (7) the massive nerve regeneration observed was functionally ineffective--these findings indicate that the total nerve damage may affect the more peripheral nerve branches.

Damage and regeneration of peripheral nerves in advanced treated leprosy.

Despite the rapidly falling prevalence of leprosy, the disability and handicap resulting from loss of protective sensation, due to irreversible nerve damage, will remain a huge medical problem for many years. To elucidate the location and consequences of permanent nerve damage in treated leprosy, a prospective study involving nine patients who underwent leg amputation was conducted. Full-length nerves dissected from amputated legs were studied with histological and immunohistochemical methods. Our main findings were that: in both lepromatous and tuberculoid leprosy nerve damage increased distally, culminating in total destruction of dermal nerves and sensory nerve endings; after the therapy-related decrease of inflammation large-scale nerve regeneration took place; and that regenerating axons persisted for decades and in tuberculoid leprosy they might reach the subcutaneous fat of the plantar skin. We conclude that nerve regeneration was blocked by fibrous replacement of the distal-most nerves and nerve endings, and that the theoretical basis of nerve grafting in leprosy is in need of further clarification. In some patients, autologous transplantation of skin flaps, probably irrespective of the duration of loss of sensation, might help in regaining protective sensation.

Mycobacteria contain two groEL genes: the second Mycobacterium leprae groEL gene is arranged in an operon with groES.

In contrast to other bacterial species, mycobacteria were thus far considered to contain groEL and groES genes that are present on separate loci on their chromosomes, Here, by screening a Mycobacterium leprae lambda gt11 expression library with serum from an Ethiopian lepromatous leprosy patient, two DNA clones were isolated that contain a groEL gene arranged in an operon with a groES gene. The complete DNA sequence of this groESL operon was determined. The predicted amino acid sequences of the GroES and GroEL proteins encoded by this operon are 85-90% and 59-61% homologous to the sequences from previously characterized mycobacterial GroES and GroEL proteins. Southern blotting analyses with M. leprae groES- and groEL-specific probes demonstrate that similar groESL homologous DNA is present in the genomes of other mycobacteria, including Mycobacterium tuberculosis. This strongly suggests that mycobacteria contain a groESL operon in addition to a separately arranged second groEL gene. Using five T-cell clones from two leprosy patients as probes, expression of the M. leprae GroES protein in Escherichia coli after heat shock was demonstrated. Four of these clones recognized the same M. leprae-specific GroES-derived peptide in a DR2-restricted fashion. No expression of the groEL gene from this operon was detected in E. coli after heat shock, as tested with a panel of T-cell clones and monoclonal antibodies reactive to previously described GroEL proteins of mycobacteria.

Peptic (contact ulcer) granuloma of the larynx.

Review of published work and analysis of clinical data and pathology of four biopsy specimens from two patients with laryngeal contact granuloma showed that its peptic origin was derived from a gastro-oesophago-laryngeal reflux. It is proposed that the term "peptic granuloma" should be given to this phenomenon. This term is given further support on account of the spectacular recovery of the laryngeal lesion following antacid and antireflux treatment, rather than the traditional method of using vocal rest and speech therapy, assumed to be the best way of treating a result of mechanical irritation, the previously accepted cause of laryngeal contact granuloma.

The caliber persistent artery of the stomach: a unifying approach to gastric aneurysm, Dieulafoy's lesion, and submucosal arterial malformation.

The caliber persistent artery of the stomach is the most dangerous form of gastrorrhagias; the overall lethality rate is 60.5%. A literature review aimed at completeness, a study of the hitherto largest case material (24 cases), and a comparative analysis of the bleeding and normal gastric arteries gave the following results: (1) the walls of the pathologic arteries are of normal structure; (2) as submucous arteries, they are of normal diameter; (3) they are attached to the mucosa by virtue of Wanke's musculoelastic mantle; (4) at the level of the muscularis mucosae, they are definitely oversized; (5) in the area of the linkage of the artery to the mucosa, a vulnerable mucosal spot is created; (6) the artery is accompanied by a vein of similar caliber; and (7) perforation of the vein takes place before that of the artery. In addition to surgical pathology and pathogenesis, the pitfalls of its diagnosis and treatment are also discussed. Caliber persistent artery of the stomach is much more common than the literature indicates, necessitating an increased awareness of the condition.

Eosinophilic endomyometritis associated with diagnostic curettage.

Histological study of hysterectomy specimens removed for noninflammatory and nonneoplastic disease revealed 15 severe cases and many more slight cases of eosinophil leukocytic endomyometritis, the degree of which appeared to correlate with injury from preoperative diagnostic curettage. In each case of severe eosinophilic endomyometritis, circumferential mucosal and extensive myometrial damage together with an occluding blood clot at the level of the inner orifice was confirmed. The massive eosinophilia appeared any time between 18 h and 21 days after curettage, and it is proposed that the probable causative agents are eosinophil chemotactic substances liberated from the myometrial mast cells and from the degrading blood clot filling the uterine cavity. There were no clinical signs or symptoms that appeared to correlate with the histological changes observed in this study. This phenomenon may serve as a model for studying the dynamics and functions of eosinophilic leukocytes in humans.

Aggressive infantile myofibromatosis: report of a case of a clinically progressive congenital multiple fibromatosis.

We report a case of congenital multiple fibromatosis (infantile myofibromatosis) showing the typical spindle-cellular proliferation with prominent vascularity on light microscopical observations. Electron microscopy showed the abundance of fibroblasts with conspicuous collagen and reticulin fibers together with numerous cells sharing the characteristics of both fibroblasts and smooth muscle cells (myofibroblasts). Neither visceral involvement nor ossification has been detected during the 4-year-long follow-up period. However, the clinical course has shown a slow, continuous, protracted though destructive proliferation of subcutaneous myofibroblastic nodules. These findings are contrasted with previous reports that claimed that the presence of myofibroblasts indicates benign behavior and results in the regression of fibromatous lesions.

Interrelationships of calibre persistent artery, chronic ulcer and squamous cancer of the lower lip.

Calibre persistent arteries come close to internal and external body surfaces without ramification or reduction of their calibre. In the stomach and jejunum they may give rise to fatal haemorrhage and in the lower lip to a chronic ulcer simulating cancer. In the present case the histological findings suggest a causal connection between an artery of persistent calibre, a chronic ulcer, and squamous cancer of the lower lip.

The validity of some morphologic methods in the diagnosis of thyroid malignancy.

The diagnostic accuracy of intraoperative frozen section and imprint cytology in thyroid conditions was analyzed along with that of cytofluorimetric nuclear DNA determination. Of 149 frozen sections in a four-year period, 90% gave a correct diagnosis, while four results were false-positive and one was false-negative. The intraoperative accuracy of imprint cytology was 95% in 309 examinations, with 12 false-positive and four false-negative results. The misjudgements with both morphologic methods derived mainly from decisions on benignancy or malignancy of follicular tumor types. Neither atypical adenoma nor encapsulated follicular carcinoma can be conclusively distinguished with these methods. Their routine application nevertheless is of great help to the surgeon, in that they can considerably reduce the need for second (radical) operations and thus the risk of complications. Nuclear DNA determination was unhelpful in the intraoperative situation.