Effect of immunotherapy with Corynebacterium parvum and methanol extraction residue of BCG administered intravenously on host defense function in cancer patients.

The effects of active nonspecific immunotherapy were studied in 42 patients receiving daily iv Corynebacterium parvum at 2 mg/m2 in 14-day courses and in 14 patients receiving iv methanol extraction residue of BCG (MER) at 0.5 mg/m2 weekly. The host defense evaluations included measurement of the number of adherent macrophage precursors per milliliter of blood (monocyte adherence), serum lysozyme, and antibody-dependent cell-mediated cytotoxicity (ADCC) of peripheral blood mononuclear cells to chicken red blood cells (CRBC) or human red blood cells (HRBC). During a single course of C. parvum, monocyte adherence did not rise significantly, whereas ADCC of peripheral blood mononuclear cells to CRBC and HRBC rose significantly (15.7-49.9% and 34.8-53.5% lysis of target cells, respectively). However, after a mean of 4.5 months on therapy, monocyte adherence increased an average of 7.5-fold. During weekly MER therapy, monocyte adherence, serum lysozyme, and ADCC of peripheral blood mononuclear cells to CRBC rose significantly within 4-7 days after the first dose (3.8-8.7 adherent cells/ml blood x 10(4), 7.6-10.8 microgram, and 34.4-41.4% target cell lysis, respectively). The host defense parameter, which was subnormal in the cancer patients (monocyte adherence), was boosted into the normal range in all the deficient patients by iv MER. The host defense parameters, which were normal or slightly elevated in the patients before therapy (serum lysozyme and ADCC of peripheral blood mononuclear cells to CRBC and HRBC), were hyperactivated above the upper limit of the normal range in 71.4, 71.4, and 50% of the patients, respectively, by iv MER. These methods can quantitatively reflect activation of monocytes and killer cells by C. parvum and MER and may be useful for evaluation and quantitation of both active nonspecific and immunorestorative immunotherapy in general.

Antiproliferative and antitumor activity of the 2-cyanoaziridine compound imexon on tumor cell lines and fresh tumor cells in vitro.

BACKGROUND: Imexon, a 2-cyanoaziridine, is therapeutic and reverses lymphadenopathy and splenomegaly in the LP-BM5 murine retrovirus-induced immunodeficiency disease (murine AIDS). It can restore chemotherapy-induced immunosuppression. Imexon reduced the incidence of lymphoma in severe combined immune deficient mice inoculated with human lymphocytes. PURPOSE: To determine its antitumor activity, we screened imexon against fresh human tumor cells and tumor cell lines. To determine the time-concentration relationships of its cytotoxicity, we studied the effects of imexon on macromolecular synthesis and on the cell cycle. METHODS: Imexon was incubated at 1-200 micrograms/mL with various tumor cell lines, mitogen-stimulated peripheral blood lymphocytes, and fresh tumor cells. Cell survival, macromolecular synthesis, and cell cycle progression were studied. RESULTS: The concentration of imexon that caused 50% inhibition of growth was under 10 micrograms/mL for lymphocytes stimulated with mitogens. It was about 3-10 micrograms/mL for B-cell lymphomas and both multi-drug-resistant and -sensitive myeloma cell lines. Imexon inhibited four of seven fresh lymphoma and 11 of 16 fresh myeloma biopsy specimens to less than 40% of the control. A 1-hour exposure of lymphoma cells to 50-100 microgram/mL followed by removal of drug by washing the cells and continuing culture resulted in greater than 95% inhibition during the next 48-72 hours. Imexon selectively inhibited protein synthesis during the first 24-48 hours of exposure of lymphoma and myeloma cells. Cells exposed to inhibitory concentrations of imexon were blocked in cell cycle progression. CONCLUSION: Imexon may be a potentially useful agent in the treatment of malignant disease, particularly lymphoid malignancies, and should be explored further.

Acute bilateral forearm compartment syndrome of unknown aetiology.

This is the first reported case of non-traumatic, acute bilateral forearm compartment syndrome. Despite a delay of over 24 hours until surgical decompression and 50% muscle fibre necrosis in the histopathological examination, the clinical outcome was excellent after fasciotomy, delayed primary wound closure and early institution of a range of motion exercise programme. The literature on non-traumatic causes of compartment syndrome is reviewed.

Increased labeling of human melanoma cells in vitro using combinations of monoclonal antibodies recognizing separate cell surface antigenic determinants.

A panel of mouse anti-melanoma monoclonal antibodies (MoAb) were analyzed for reactivity with human melanoma cells singly and in combination. Five MoAb, ZME-018, 96.5, P94, 4.2, and 5.1, reactive with individual cell surface melanoma-associated antigens were tested with seven melanoma cell lines and seven fresh tumor biopsies. Cells were incubated with the MoAb, indirectly stained with fluorescein-conjugated goat anti-mouse immunoglobulin, and analyzed by flow cytometry. Percentage of labeled cells and relative fluorescence intensity (FI) with individual MoAb varied with different cell lines and biopsy samples. The most reactive MoAb, ZME-018, 96.5, and P94, labeled 29-93% of the cells from cell lines with relative FI of 2-59 units, thereby demonstrating phenotypic diversity of these cells. Similar results were obtained with cells derived from tumor biopsies, where 1-73% of cells were labeled and relative FI ranged from 0-27. These variations were reduced by using a "cocktail" of MoAb which recognized different melanoma-associated antigens. In cell lines both the percentage of labeled cells (range, 82-95%) and relative FI (range, 36-115) increased substantially (P less than 0.025 and P less than 0.005, respectively) when a "cocktail" prepared from all five MoAb rather than individual MoAb was used. A cocktail of MoAb increased the percentage of labeled tumor biopsy cells (range, 53-78; P less than 0.01) and relative FI (range, 11-69; P less than 0.025). The mean FI obtained by incubating cells with a cocktail of suboptimal concentrations of three MoAb (ZME-018, 96.5, P94) was 48 +/- 12 (SD), which was significantly increased compared to the mean FI seen with suboptimal concentrations of MoAb alone (ZME-018, 7 +/- 10; 96.5, 8 +/- 7; P94, 2 +/- 2; P less than 0.005). These findings were confirmed by radioimmunoassay using a combination of two MoAb, ZME-018 and 96.5. The data suggest that cocktails of MoAb were more effective than single MoAb alone for melanoma tumor cell labeling in vitro and might be more effective for tumor imaging and therapy.

Synergistic control of stimulated pronosupination with the stimulated grasp of persons with tetraplegia.

The control of stimulated forearm pronosupination in concert with stimulated hand grasp of persons with tetraplegia has been investigated. It has been shown that hand grasp stability increased as supination was achieved. In accordance with this, a strategy of object acquisition has been proposed incorporating pronosupination and hand grasp. It has been proposed that, after object acquisition in the pronated posture, that supination be used to increase grasp stability. Three types of pronosupination control which act in synchrony with grasp were implemented incorporating this principle. The three types used were position-controlled pronator stimulation, touch-controlled pronator stimulation, and constant pronation stimulation. These controllers played a supporting role to the separate user control of hand grasp and release. The three controllers were evaluated and compared using a standardized test procedure that incorporated stimulated pronosupination control with stimulated grasp. Such methods of pronosupination control are likely to provide enhanced options for improving upper extremity function using electrical stimulation.

Control of a hand grasp neuroprosthesis using an electroencephalogram-triggered switch: demonstration of improvements in performance using wavepacket analysis.

Volitionally modulated electroencephalographic (EEG) waves were monitored for the purpose of controlling a hand neuroprosthesis in people with tetraplegia. The region of the EEG signal spectrum monitored was the occipital alpha wave (8-13 Hz), and volitional modulation was achieved with the opening and closing of the eyes. In a set of 13 trials evaluated, a subject with tetraplegia successfully completed ten trials undertaking stimulated grasp and release using the EEG-triggered switch. EEG signal data recorded during the 13 trials were also post-processed off-line using wavepacket analysis. Following this signal processing, the speed and reliability of the EEG-triggered switch, when operated by the subject with tetraplegia, was significantly improved (p < 0.002). Such improvements provide system performance that is likely to be acceptable to a neuroprosthesis user during activities of daily life.

Surgery for cerebral palsy: Part 1. Classification and operative procedures for pronation deformity.

32 patients with cerebral palsy underwent operations for pronation deformity. The deformity is classified into four groups. Patients in group 1 are capable of supination beyond neutral. No surgery is necessary. Those in group 2 are able to supinate to the neutral position. A pronator quadratus release is advised and may be combined with a flexor aponeurotic release. In group 3, patients have no active supination. However a full range of passive supination is readily achieved. A pronator teres transfer is advised. Patients in group 4 have no active supination. Full passive supination may be present, but is tight. A flexor aponeurotic release and a pronator quadratus release may unmask active supinator activity. An active transfer for supination is possible as a secondary procedure.

Surgery for cerebral palsy: Part 2. Flexion deformity of the wrist and fingers.

34 children with cerebral palsy had operations to correct flexion deformities of the wrist and fingers. 30 out of 34 patients were improved functionally and cosmetically. Zancolli's classification provides sound guidelines on which to base surgical decisions.

Selective motor neuropathy of the median nerve caused by a ganglion in the carpal tunnel.

Carpal tunnel syndrome is the commonest peripheral compressive neuropathy. Typically, sensory symptoms predominate at presentation with motor dysfunction seen in more chronic cases. Isolated motor compression is rare. We present a case of selective median nerve motor neuropathy caused by a carpal tunnel ganglion.

Does peri-operative guanethidine prevent reflex sympathetic dystrophy?

The use of intravenous guanethidine blocks is an accepted treatment for established reflex sympathetic dystrophy (RSD). Some units administer intravenous guanethidine peri-operatively with the intention of protecting their patients from post-operative dystrophy. There have been no studies confirming this protective effect of peri-operative guanethidine. Between 1992 and 1994 we performed a prospective randomized double blind study in 71 patients undergoing fasciectomy for Duputyren's disease. Peri-operative guanethidine did not prevent post-operative RSD in our series.

Wrist arthrodesis using a sliding radial graft and plate fixation.

In a retrospective study, the results of 18 wrist fusions with a radial sliding graft and a dynamic compression plate are reviewed. All 18 fusions united, with an average position of 16 degrees of extension and 7 degrees of ulnar deviation. Wrist strength and stability and diminished pain allowed improved function. However, decreased maneuverability impaired function for some activities.

[Classification and surgical treatment of pronation deformity in cerebral palsy]. / Klassifikation und operative Behandlung der Pronationsdeformität bei Zerebralparese.

A clinically simple and logical classification of pronation deformity in cerebral palsy into four groups is presented. The appropriate procedure for each group is defined. The validity of this classification is documented with our results in 32 patients.

Outcome of axillary nerve injuries treated with nerve grafts.

This study evaluates the outcome of axillary nerve injuries treated with nerve grafting. Thirty-six patients were retrospectively reviewed after a mean of 53 months (minimum 12 months). The mean interval from injury to surgery was 6.5 months. Recovery of deltoid function was assessed by the power of both abduction and retropulsion, the deltoid bulk and extension lag. The deltoid bulk was almost symmetrical in nine of 34 cases, good in 22 and wasted in three. Grade M4 or M5* was achieved in 30 of 35 for abduction and in 32 of 35 for retropulsion. There was an extension lag in four patients. Deltoid bulk continued to improve with a longer follow-up following surgery. Nerve grafting to the axillary nerve is a reliable method of regaining deltoid function when the lesion is distal to its origin from the posterior cord.