Renal Cell Carcinoma in Renal Transplantation: The Case for Surveillance.

INTRODUCTION: Between January 2013 and September 2015, 135 consecutive renal transplant patients were screened prospectively with ultrasound for renal cell carcinoma (RCC). RESULTS: Eighteen ultrasound abnormalities were identified with 4 solid lesions detected. Fifty-six other patients were screened retrospectively by referring nephrology groups, with 6 additional malignancies found. CONCLUSION: As a result of our data, we recommend and have instituted annual ultrasound screening of native kidneys in all renal transplant patients.

Early Post-transplant Lymphoproliferative Disease in the Donor Ureter Without Systemic Involvement: A Case Report.

BACKGROUND: Post-transplant lymphoproliferative disease is a serious complication of renal transplantation. Major risk factors include Epstein-Barr virus (EBV) seronegativity and induction immunosuppression with lymphocyte-depleting agents. RESULTS: We present a case of a 50-year year-old woman with very early onset PTLD confined to the donor ureter. Phenotypic studies on the tumor material reveal that the lymphoma was most likely of donor origin. A complete staging workup including the kidney allograft was negative for any other sites of involvement. CONCLUSIONS: This case, which had a fatal outcome, emphasizes the risk of renal transplantation in BV-negative individuals when given induction with lymphocyte-depleting drugs.

TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.

OBJECTIVE: To improve understanding of TRPV4-associated axonal Charcot-Marie-Tooth (CMT) neuropathy phenotypes and their debated pathologic mechanism. METHODS: A total of 17 CMT2C phenotypic families with vocal cord and diaphragmatic involvement and 36 clinically undifferentiated CMT2 subjects underwent sequencing analysis of the coding region of TRPV4. Functional studies of mutant proteins were performed using transiently transfected cells for TRPV4 subcellular localization, basal and stimulated Ca(2+) channel analysis, and cell viability assay with or without channel blockade. RESULTS: Two TRPV4 mutations R232C and R316H from 17 CMT2C families were identified in the ankyrin repeat domains. The R316H is a novel de novo mutation found in a patient with CMT2C phenotype. The family with R232C mutation had individuals with and without vocal cord and diaphragm involvement. Both mutant TRPV4 proteins had normal subcellular localization in HEK293 and HeLa cells. Cells transfected with R232C and R316H displayed increased intracellular Ca(2+) levels and reversible cell death by the TRPV channel antagonist, ruthenium red. CONCLUSION: TRPV4 ankyrin domain alterations including a novel de novo mutation cause axonal CMT2. Individuals with the same mutation may have nondistinct CMT2 or have phenotypic CMT2C with vocal cord paresis. Reversible hypercalcemic gain-of-function of mutant TRPV4 instead of loss-of-function appears to be pathologically important. The reversibility of cell death by channel blockade provides an attractive area of investigation in consideration of treatable axonal degeneration.

Use of organs for transplantation from a donor with primary meningoencephalitis due to Naegleria fowleri.

Naegleria fowleri is a free-living amebic organism that causes acute meningoencephalitis and brain death in young people. Though this infection is limited to the central nervous system, organ donation is usually ruled out because of the infectious nature of the donor's death. Based on the realization that this organism is limited to the brain, we successfully transplanted organs from a 12-year-old male donor dying of N. fowleri infection. Kidneys, pancreas, a lung and liver were used with no evidence of posttransplant infectious complications. This unusual cause of brain death does not preclude successful organ donation.

Intrathecal baclofen therapy in stiff-man syndrome: a double-blind, placebo-controlled trial.

We performed a double-blind, placebo-controlled trial of intrathecal baclofen (ITB) in stiff-man syndrome. Three patients, unresponsive to current therapy, received 50 micrograms of ITB or placebo on sequential days. Following ITB, all patients demonstrated improvement in reflex EMG activity. The mean reduction in total EMG activity (from all muscles) following stimulation of the medial plantar nerve (cutaneous flexor reflex) was 72% following 50 micrograms of ITB compared with 18% following placebo (ANOVA: significance of F, p < 0.0001). The mean latency to onset of the response was also significantly prolonged for all muscles following ITB (ANOVA: significance of F, p < 0.05). Although reflex EMG activity was reduced in all patients, clinical improvement was evident in only one patient, who differed from the others studied by a longer duration of disease, greater severity of stiffness, less fear of falling, and greater electrophysiologic improvement.

The acoustic startle reflex in stiff-man syndrome.

We studied the EMG response to loud noise in eight patients with stiff-man syndrome (SMS). Audiogenic muscle jerks originated in the acoustic startle reflex. Patients demonstrated excessive, poorly habituating motor activity predominantly in axial and leg muscles. Exaggerated startle in SMS probably reflects segmental hyperexcitability of axial and lumbar spinal motor neurons.

Diagnosis and treatment of Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome is a rare autoimmune neuromuscular and autonomic disease that produces fluctuating muscle weakness, hyporeflexia, and autonomic dysfunction, and often is associated with small-cell lung cancer. The pathophysiology is understood quite well; antibodies to voltage-gated calcium channels in motor and autonomic nerve terminals disrupt calcium influx and reduce acetylcholine release. The diagnosis may be suspected clinically, but must be confirmed with electrophysiologic testing. Initial and then periodic screening for malignancy is essential. Tumors other than small-cell lung cancer occasionally are found. Effective tumor treatment may induce remission. Active disease may respond to agents that enhance neuromuscular transmission or to immunosuppression. Combined therapy frequently is needed and control is often marginal despite this. It is expected that availability of 3,4-DAP will improve significantly the response to treatment in most patients.

Human type A botulism and treatment with 3,4-diaminopyridine.

3,4-diaminopyridine was evaluated for its ability to improve muscle strength, respiratory function and electromyographic compound muscle action potentials in human botulism. In a double blind, placebo controlled study, 3,4-diaminopyridine failed to improve these parameters in a 31-year old patient with severe food-borne type A botulism. The addition of an anti-cholinesterase medication to the 3,4-diaminopyridine did not add any benefit. Lack of clinical improvement from 3,4-diaminopyridine in this patient differed from some reports of benefit in animals experimentally poisoned with type A botulinum toxin.

Stiff-man syndrome.

Stiff-man syndrome (Moersch-Woltman syndrome) is a rare disorder of motor function characterized by involuntary stiffness of axial muscles and superimposed painful muscle spasms, which are often induced by startle or emotional stimuli. The standard treatment has been benzodiazepines. An association has been reported between stiff-man syndrome and epilepsy, insulin-dependent diabetes, and a variety of organ-specific autoimmune disorders. Antibodies directed against glutamic acid decarboxylase and against pancreatic islet cells have been detected in the serum and cerebrospinal of patients with stiff-man syndrome. These findings suggest that stiff-man syndrome may be an autoimmune disease. Preliminary reports indicate that patients with stiff-man syndrome have a favorable response to plasma exchange and corticosteroid therapy.

Clinical neurophysiologic studies in stiff-man syndrome: use of simultaneous video-electroencephalographic-surface electromyographic recording.

Three patients with a clinical diagnosis of stiff-man syndrome were studied with simultaneous video-electroencephalographic-surface electromyographic recordings in addition to routine electromyography in order to obtain objective data to confirm their diagnosis, to improve our understanding of the diagnosis of stiff-man syndrome, and to define reproducible clinical and neurophysiologic criteria for the stiff-man syndrome. These patients had the following features of this syndrome: (1) continuous muscle activity that varied with awake and sleep states, posture, passive and active movements, and medications; (2) superimposed intermittent generalized contractions while awake, which continued into drowsiness and interfered with onset of sleep; and (3) abnormal cocontractions of antagonistic muscles. The characteristic findings in the stiff-man syndrome can be recorded by using video-electroencephalographic-surface electromyographic techniques, a useful application of equipment already available in most electroencephalography laboratories. Neurophysiologic techniques can help in elucidating the clinical findings in the stiff-man syndrome. Further systematic study in patients before and during treatment is needed to identify common diagnostic criteria for this syndrome.

3,4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome is characterized by muscle weakness, hyporeflexia, and autonomic dysfunction, which result from impaired release of acetylcholine from cholinergic nerve terminals. It is frequently associated with cancer, it is autoimmune-mediated, and treatment has been unsatisfactory. 3,4-Diaminopyridine enhances the release of acetylcholine. In this prospective, double-blind, placebo-controlled crossover study of 12 patients with Lambert-Eaton myasthenic syndrome (7 of whom had cancer), 3,4-diaminopyridine in doses up to 100 mg per day was effective in treating both the motor and the autonomic deficits of the syndrome. Muscle strength increased from an average of 70 percent of normal to 81 percent of normal in the upper extremities, and from 45 to 65 percent of normal in the lower extremities. The amplitudes of compound-muscle-action potentials nearly doubled, increasing from an average of 2.9 mV to 5.0 mV in the arm and from 1.6 mV to 3.1 mV in the leg. Autonomic symptoms were relieved. One patient had a seizure after 10 months of treatment, but other side effects from the drug were minimal and dose-related. We conclude that 3,4-diaminopyridine, either alone or in conjunction with other therapies, may be useful in the treatment of Lambert-Eaton myasthenic syndrome.