An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis.

BACKGROUND: Voltage-gated potassium channel antibody-positive limbic encephalitis (VGKC+LE) frequently improves with immunotherapy, although the optimum regimen is unknown. The effectiveness of a combination immunomodulatory regimen was tested in consecutive VGKC+LE patients. METHODS: This was an open-label prospective study of nine VGKC+LE patients. All patients had plasma exchange (50 ml/kg), intravenous immunoglobulin (2 g/kg) and intravenous methylprednisolone (1 g×3), followed by maintenance oral prednisolone (1 mg/kg/day). Mycophenolate (2 g/day) was used in the first three patients. Assessments included serial clinical, cognitive, brain MRI and VGKC antibody testing. RESULTS: Within 1 week, seizures and hyponatraemia remitted in all affected patients. Cognitive function improved in all patients within 3 months. MRI appearances improved substantially within 9 months, with remission of inflammation in the majority of patients. All achieved immunological remission with normal VGKC antibody titres within 1-4 months. Major adverse events of therapy included one septicaemia and one thrombosis on plasma exchange and one death from sepsis after incidental bowel surgery. One patient remains in remission after 40 months of follow up, 26 months after being off all treatment. CONCLUSIONS: Our immunotherapy regimen was effective for the treatment of the clinical, cognitive and immunological features of VGKC+LE. Radiological improvement was seen in the majority. Pending randomised controlled trials, this regimen is proposed for the treatment of VGKC+LE.

Systematic review: acute colonic pseudo-obstruction.

Acute colonic pseudo-obstruction is the clinical syndrome of acute large bowel dilatation without mechanical obstruction that is an important cause of morbidity and mortality. Acute colonic pseudo-obstruction occurs in hospitalized or institutionalized patients with serious underlying medical and surgical conditions. The pathogenesis of acute colonic pseudo-obstruction is not completely understood but likely results from an imbalance in the autonomic regulation of colonic motor function. Metabolic or pharmacological factors, as well as spinal or retroperitoneal trauma, may alter the autonomic regulation of colonic function, leading to excessive parasympathetic suppression or sympathetic stimulation. This imbalance results in colonic atony and dilatation. Early recognition and appropriate management are critical to minimizing morbidity and mortality. The mortality rate is estimated at 40% when ischaemia or perforation occurs. The best-studied treatment of acute colonic pseudo-obstruction is intravenous neostigmine, which leads to prompt colon decompression in the majority of patients after a single infusion. In patients failing or having contraindications to neostigmine, colonoscopic decompression is the active intervention of choice. Surgery is reserved for those with peritonitis or perforation.

Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987-1997: incidence, causes, and outcome.

OBJECTIVE: Severe GI bleeding after hematopoietic cell transplantation is commonly due to lesions that are unusual in nontransplant patients. The frequency of GI bleeding appears to have decreased over the last decade, but the reasons have not been readily apparent. We sought to determine the incidence of severe bleeding during two time periods, to describe the causes and outcomes of bleeding, and to analyze the reasons behind an apparent decline in severe bleeding over the decade covered. METHODS: During 1986-1987 and 1996-1997, we followed all patients with and without severe bleeding at our institution, a marrow transplant center. RESULTS: Over this decade, the incidence of severe bleeding declined from 50/467 (10.7%) to 15/635 (2.4%) (p < 0.0001). Overall mortality from intestinal bleeding declined from 3.6% to 0.9% (p = 0.002), but mortality in those with bleeding remained high (34% vs 40%). The onset (day 42 vs 47) and platelet counts (35,994 vs 37,600/microl) were similar, but the sites and causes of bleeding were different. During 1986-1987, 27/50 patients bled from multiple GI sites, viral and fungal ulcers, or graft-versus-host disease (GVHD). Over the decade, bleeding from GVHD had decreased 80% (p < 0.0001), and bleeding from viral (p < 0.0001) and fungal (p = 0.023) ulcers almost disappeared. CONCLUSIONS: The incidence of severe GI bleeding has declined significantly over the last decade because of prevention of viral and fungal infections and severe acute GVHD. However, severe bleeding after transplant remains a highly morbid event, particularly among patients with GVHD.

Bile duct apoptosis and cholestasis resembling acute graft-versus-host disease after autologous hematopoietic cell transplantation.

BACKGROUND: Acute graft-versus-host disease (GVHD) of the liver is a frequent complication of allogeneic hematopoietic cell transplantation. This report describes hepatic GVHD following autologous transplantation. METHODS: We reviewed 116 consecutive autologous transplant recipients. A diagnosis of GVHD was based on histology (segmental to subtotal destruction of bile ductal epithelial cells with apoptosis and lymphocytic infiltrates), clinical criteria (elevated serum alkaline phosphatase), a response to immunosuppressive therapy, and finding no other cause for cholestatic liver disease. RESULTS: Two patients developed cholestatic liver disease (alkaline phosphatase levels over five times the normal upper limit) and had liver biopsies showing apoptotic and dysmorphic ductular epithelial cells typical of GVHD. Three additional patients developed cholestasis and intestinal symptoms but had gastric biopsies only, showing apoptotic crypt epithelial cells and crypt cell drop-out typical of GVHD. CONCLUSION: Two recipients of autologous hematopoietic cells developed histologic abnormalities of small bile ducts and cholestatic liver disease resembling GVHD of the liver after allogeneic transplant. The mechanisms of bile duct damage in this setting may involve immune dysregulation related to reconstitution of immunity with peripheral blood stem cells.

Neostigmine for the treatment of acute colonic pseudo-obstruction.

BACKGROUND: Acute colonic pseudo-obstruction -- that is, massive dilation of the colon without mechanical obstruction -- may develop after surgery or severe illness. Although it may resolve with conservative therapy, colonoscopic decompression is sometimes needed to prevent ischemia and perforation of the bowel. Uncontrolled studies have suggested that neostigmine, may be an effective treatment. METHODS: We studied 21 patients with acute colonic pseudo-obstruction. All had abdominal distention and radiographic evidence of colonic dilation, with a cecal diameter of at least 10 cm, and had had no response to at least 24 hours of conservative treatment. We randomly assigned 11 to receive 2.0 mg of neostigmine intravenously and 10 to receive intravenous saline. A physician who was unaware of the patients' treatment assignments recorded clinical response (defined as prompt evacuation of flatus or stool and a reduction in abdominal distention), abdominal circumference, and measurements of the colon on radiographs. Patients who had no response to the initial injection were eligible to receive open-label neostigmine three hours later. RESULTS: Ten of the 11 patients who received neostigmine had prompt colonic decompression, as compared with none of the 10 patients who received placebo (P<0.001). The median time to response was 4 minutes (range, 3 to 30). Seven patients in the placebo group and the one patient in the neostigmine group without an initial response received open-label neostigmine; all had colonic decompression. Two patients who had an initial response to neostigmine required colonoscopic decompression for recurrence of colonic distention; one eventually underwent subtotal colectomy. Side effects of neostigmine included abdominal pain, excess salivation, and vomiting. Symptomatic bradycardia developed in two patients and was treated with atropine. CONCLUSIONS: In patients with acute colonic pseudo-obstruction who have not had a response to conservative therapy, treatment with neostigmine rapidly decompresses the colon.

Comparison of reinforcement schedules in the reduction of stereotypy with supported routines.

The rates and durations of stereotypic behaviors in four adolescents with severe mental retardation were measured during two daily vocational training sessions and during contiguous periods of leisure in their special education classrooms. Vocational training was conducted in two different tasks, alternating across days. The task requirements for each participant were matched to each participant's learning and performance characteristics. The participants were exposed to a fixed ratio schedule of tokens exchangeable for food items on one task and to a variable interval schedule for the same consequences on the second task. The schedules were chosen as an initial test of a matching-law based prediction by Myerson and Hale (1984): Variable interval reinforcement for adaptive behavior will produce less allocation of responding to maladaptive behavior than will a ratio-based intervention. When work performances stabilized, the schedules of token delivery were reversed across the tasks and performances again stabilized. Results are reported for periods when work performances met stability criteria. Stereotypy occurred more during leisure than during vocational training under either schedule. The major differences in stereotypy between leisure and vocational training were differences in episode length rather than rate of onset. Onset of stereotypy in vocational training, however, occurred at higher rates under the interval schedule than under the ratio schedule in both tasks. The results are discussed in terms of Myerson and Hale's prediction and implications for further research and application.

A program evaluation of classroom data collection with bar codes.

A technology incorporating bar code symbols and hand-held optical scanners was evaluated for its utility for routine data collection in a special education classroom. A different bar code symbol was created for each Individualized Educational Plan objective, each type of response occurrence, and each student in the first author's classroom. These symbols were organized by activity and printed as data sheets. The teacher and paraprofessionals scanned relevant codes with scanners when the students emitted targeted behaviors. The codes, dates, and approximate times of the scans were retained in the scanner's electronic memory until they could be transferred by communication software to a computer file. The data from the computer file were organized weekly into a printed report of student performance using a program written with commercially available database software. Advantages, disadvantages, and costs of using the system are discussed.

Beneficial effects of glucose polymer and an H2-receptor blocker in a patient with a proximal ileostomy.

A patient with an ileocolectomy and proximal ileostomy for Crohn's disease had severe diarrhea and steatorrhea. An oral electrolyte solution containing glucose polymer was shown to improve water and electrolyte absorption. Ileal contents were abnormally acidic. Therapy with an H2-receptor blocker raised ileal pH, improved the efficiency of fat absorption, and promoted a gain in body weight.