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Gene expression in archived frozen sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was compared to that in vasculitic nerve biopsies (VAS) and to normal nerve (NN) by DNA microarray technology. Hierarchical clustering analysis demonstrated distinct gene expression patterns distinguishing these disease groups. Of particular interest were: (1) Tachykinin precursor 1, which may be involved in pain mediation; (2) Stearoyl-CoA-desaturase, which may be a marker for remyelination and (3) the Allograft Inflammatory Factor 1 (AIF-1), a modulator of immune response during macrophage activation. Differential gene expression may help distinguish between CIDP, VAS and NN in sural nerve biopsies and identify genes that may be involved in disease pathogenesis.

Estrogens (E) and progesterone (P) are known to require their respective steroid receptors in order to exert structural and functional effects on the oviduct. Cyclic changes in progesterone receptor (PR) localization in the oviductal tissue of female pigs were determined using an immunohistochemical technique with mouse monoclonal antibody mPRI against PR. The variations observed during the estrous cycle in the progesterone receptor (PR) intensity and proportion between ampulla and isthmus probably reflect different response of these regions to progesterone. Immediately before ovulation, during follicular phase, no staining was observed in either the ampulla or the isthmus stroma. However, a low expression of PR in the epithelium of the ampulla was observed. After ovulation, during luteal phase, PR immunostaining was more intense in the whole oviduct. According to immunohistochemical assays, the binding assays for nuclear and cytosolic PR (PRn and PRc, respectively), by using [3H] R5020 at 4 degrees C for 15 h, also showed a higher specific binding during luteal phase. However, the PR mRNA in the oviduct, analyzed by RT-PCR, showed similar levels at both stages of the estrous cycle. Although this methods could not be quantitative, indicate the possibility that a post-transcriptional control could differentially regulate the PR in the pig oviduct.

A 48-year-old man with an IgM plasma cell dyscrasia died after 14 months of symptoms and signs typical of motor neuron disease, including widespread fasciculation and normal sensation. Two laboratory results were atypical: cerebrospinal fluid protein content of 132 mg/dl and slow motor nerve conduction. At autopsy, no loss or atrophy of anterior horn neurons was found; instead, degeneration of ventral and dorsal roots and retrograde changes of chromatolysis in motor neurons implied peripheral neuropathy. Most reported cases of neuropathy associated with plasma cell dyscrasias have been sensorimotor or purely sensory, but there have been 14 previous cases of motor disorders.

A 67-year-old man with prostate cancer presented with acute polymyositis and vocal cord paralysis as a result of mediastinal lymphadenopathy. His clinical course was unusual, with the development of a malignant pleural effusion, supraclavicular adenopathy, and osteolytic bone lesions. Urologic symptoms developed only pre-terminally, and osteoblastic bone metastases were not documented. This case suggests that prostate cancer need not have a simple natural history.

Thirteen patients with polyneuropathy associated with plasma cell dyscrasia had serial electrophysiological studies. Five patients with monoclonal IgG had motor and/or sensory symptoms of which 4 correlated with slow motor and sensory nerve conduction. The 4 patients with monoclonal IgM reactive with myelin-associated glycoprotein (MAG), had predominantly motor symptoms, demyelination in the nerve biopsy and slow motor and sensory nerve conduction. Four patients with monoclonal IgM without anti-MAG activity had mainly sensory symptoms, axonal neuropathy on nerve pathology and slow or absent sensory nerve conduction. After treatment with plasmapheresis and chemotherapy 9 patients improved clinically and 4 were unchanged. Criteria for electrophysiologic improvement were presence of sensory or motor responses that were absent before treatment, conduction velocity increased by more than 10 m/s and increase of amplitude by more than 100%. Electrophysiological studies showed improvement in 7, were unchanged in 4, and worse in 2. Sensory velocities in ulnar and sural nerves were significantly improved following treatment (P less than 0.002) and the same trend was noted for the sensory velocity in the median nerve (P less than 0.19). We conclude that nerve conduction studies in combination with clinical examinations are useful in documenting the effects of treatment in these neuropathies.

Serum from patients with peripheral neuropathies was tested for antiperipheral nerve myelin antibodies by complement fixation. Antibody activity was detected in 5 of 20 patients with acute or chronic remitting polyneuritis and in 4 of 20 patients with polyneuropathy and paraproteinemia but not in patients with other types of neuropathy, neurologic disease, or immunologic disease. In three patients with IgM paraproteinemia, the complement-fixing activity resided in the IgM fraction; in one patient with chronic inflammatory polyneuritis, antibody activity resided in the IgG fraction. In the inflammatory polyneuropathies, antibody titers did not always correlate with disease activity. Sera from patients with remitting polyneuropathies reacted with either human or rabbit peripheral nerve myelin, but sera from patients with paraproteinemia reacted only with human myelin.

Six patients had peripheral neuropathy and nonmalignant IgM plasma cell dyscrasia. In two of them, immunological studies indicated that the monoclonal immunoglobulin reacted with myelin-associated glycoprotein, a constituent of peripheral nerve myelin. Sural nerve biopsy specimens from both patients showed morphological signs of primary damage to the myelin sheath. In the other four patients, two of whom had a monoclonal IgMK reactive with chondroitin sulfate C, the axon rather than the myelin sheath was considered the chief site of nerve injury. The morphological findings suggest that the pathogenesis of peripheral neuropathies in IgM plasma cell dyscrasia is heterogeneous. Moreover, the observations are consistent with a pathogenic interaction of the IgM paraprotein with autoantigens in peripheral nerve in some instances.

In an effort to determine if there might be an association between Guillain-Barré syndrome and specific antigens of the HLA system, 18 patients with Guillain-Barré syndrome were typed for HLA-A, B, and D antigens. No statistically significant relationship was established by this study.

Thymectomy has been shown to be effective in the treatment of myasthenia gravis. The logical goal of operation has been complete removal of the thymus, but there has been controversy about the surgical technique and its relation to results. Surgical-anatomic studies have shown gross and microscopic thymus widely distributed in the neck and mediastinum. We believe that an en bloc transcervical-transsternal "maximal" thymectomy is required to remove all thymic tissue predictably. Ninety-five patients with generalized myasthenia gravis underwent "maximal" thymectomy consecutively between 1977 and 1985 and were evaluated 6 months to 89 months after operation. In Group A (N = 72), myasthenia gravis without thymoma, the uncorrected data revealed that 96% (69) had benefited from operation: 79% (57) had no symptoms; 46% (33) were in remission; 33% (24) were symptom free when receiving minimal doses of pyridostigmine; and none were worse. Life table analysis yielded a remission rate of 81% at 89 months. In group B (N = 8), myasthenia gravis without thymoma for which patients underwent reexploration for incapacitating weakness after earlier transcervical or transsternal operations, residual thymus was found in all. One patient was in remission, two were symptom free when receiving medication, one was unchanged, and none were worse. In group C (N 15), myasthenia gravis and thymoma, two patients were in remission and nine were symptom free when receiving medication. Two patients in this group died 2 and 4 years postoperatively in crisis. Response to thymectomy in group A was greater in patients with mild myasthenia gravis and may have been better in patients who had symptoms for less than 60 months preoperatively, but the response did not depend on age, sex, presence or absence of thymic hyperplasia or involution, or titers of acetylcholine receptor antibodies. The response to thymectomy in group B was striking but slower than in group A, perhaps because symptoms were more severe and of longer duration. The response in group C was also less good than in group A and proportionately fewer benefited. These results support the recommendation for thymectomy in the treatment of patients with generalized myasthenia gravis and indicate the desirability of a maximal procedure. For persistent or recurrent severe symptoms after previous transcervical or submaximal transsternal resections, reoperation by this technique is also recommended.

A case of Becker's nevus occurring in association with an accessory scrotum is described. Recent studies have shown the presence of androgen receptors in Becker's nevus in concentrations comparable to those in genital skin. We postulate that the simultaneous occurrence of both these developmental anomalies was manifested because of androgen sensitivity and stimulation.

Hypopigmented skin spots, resembling the mountain ash leaf, may represent the earliest sign in tuberous sclerosis. We examined two patients with hypopigmented iris spots who suffered from this systemic disease. These iris spots may be analogous to the skin lesions, which have decreased amount of melanin in the melanosomes.

Thymectomy is important in the treatment of myasthenia gravis. Total removal of the gland is considered indicated. Although median sternotomy has been the accepted surgical procedure, the transcervical approach has been advocated as a safer method of achieving total thymectomy. A surgical-anatomical study of the thymus was made in 22 patients. A high incidence of surgically important variations in thymic anatomy was found in the neck and in the mediastinum. We believe wide exposure by way of median sternotomy with direct vision is required to remove all of the extracapsular mediastinal thymus in many patients, and good cervical exposure is required to remove the anomalous tissue in the neck. If a total thymectomy is to be achieved, we recommend a median sternotomy and a cervical incision, using the meticulous dissection described.

Plasma exchange was used to treat 10 patients with polyneuropathy and a monoclonal antibody (plasma cell dyscrasia). Six patients had improvement of the neuropathy, while three patients had stabilisation of the neuropathy during plasma exchange. The patients who improved maintained a 64% or greater decrease in the monoclonal antibody between exchanges. Patients with axonal polyneuropathy as well as patients with demyelinating polyneuropathy recovered some neurologic function. With cessation of plasma exchanges, the monoclonal antibody titre approached pre-treatment levels and the neuropathy progressed. Plasma exchange was effective in rapidly lowering the level of monoclonal antibody and allowing for some recovery of neurologic function.

We studied a patient with hypocalcemia and increased serum activity of sarcoplasmic enzymes. Idiopathic hypoparathyroidism was established by history, low serum parathyroid hormone content, and marked responsiveness of urinary cyclic AMP and phosphate to parathyroid hormone. Muscle-associated isoenzymes of creatine phosphokinase and lactic dehydrogenase were increased, but there was no concomitant muscle weakness. Muscle biopsy was normal by morphologic and histochemical examination. The patient was treated with calcium and vitamin D. As the calcium rose, there were corresponding decreases in the serum activities of creatine phosphokinase and lactic dehydrogenase, with correlation coefficients of -0.88 and -0.64, respectively (p less than 0.01).

Sixty-six patients with amyotrophic lateral sclerosis (ALS) participated in a double-blind, placebo-controlled study of transfer factor. A structured rating score of neurological function was recorded after each monthly administration of transfer factor or placebo. Statistical analysis of mean scores for all patients and for those with specific clinical abnormalities showed no significant difference between the two groups. There was no evidence of therapeutic value for transfer factor. During the observation period of nearly one year, more than two-thirds of the deterioration occurred in the first six months. Meaningful clinical trials of other potential therapeutic agents could probably be conducted within six months in double-blind crossover trials.

Fifty-nine patients with amyotrophic lateral sclerosis participated in a 12-month, double-blind crossover trial. The patients were given either levamisole 150 mg or placebo in identical tablets once a week orally, and a rating of neurologic signs and symptoms was recorded on monthly visits. The patients were crossed over at 6 months. Levamisole had no effect on the rate of score decline in the 20 patients who completed the trial.