Neural therapy in the treatment of multiple sclerosis.

OBJECTIVE: To assess the therapeutic potential of neural therapy, a modified form of acupuncture, in multiple sclerosis. DESIGN: A pilot study followed by a double-blind, placebo-controlled randomized study. SETTING: The Glasgow Homoeopathic Hospital, Glasgow, Scotland. PATIENTS: An unselected group of 61 new patients referred to the Glasgow Homoeopathic Hospital, suffering from any type of multiple sclerosis, who fulfilled the criteria of Schumacher and had a Disability Status Score (DSS) or Expanded Disability Status Score (EDSS) grade of 1-7. INTERVENTION: Neural therapy, which is the injection of small amounts of local anesthetic without adrenaline, into specific trigger points in the ankles and around the greatest circumference of the skull. MAIN OUTCOME MEASURES: Improvements in the Kurtzke scales and the DSS or EDSS assessments. RESULTS: Sixty-five percent (65%) of the patients in the pilot study (n = 40) and seventy-six percent (76%) of the patients in the double-blind trial (n = 21) benefitted from this treatment as assessed by Kurtzke scale improvements. On long-term follow-up of 2.0 to 3.5 years, more than 50% of the patients continued to show improved Kurtzke scale ratings. Improvements could be rapid. No toxic side effects were noted when injections were administered at a frequency of once or twice weekly or less. CONCLUSIONS: Neural therapy is an effective, nontoxic and inexpensive treatment for multiple sclerosis that can confer both immediate and long-term benefits.

Immunologic effects of insulin lispro [Lys (B28), Pro (B29) human insulin] in IDDM and NIDDM patients previously treated with insulin.

Insulin lispro [Lys (B28), Pro (B29) human insulin] is a rapidly absorbed analog that has diminished tendency to self-associate. In four open-label, 1-year-long international randomized trials, we contrasted the immunogenicity of insulin lispro versus regular human insulin (RHI) in patients previously treated with insulin who had IDDM or NIDDM. Using a self-blank subtraction assay, we assessed sera for the presence of insulin-specific antibodies (ISA), insulin lispro-specific antibodies (LSA), and cross-reactive antibodies (CRA). Basal insulin needs were provided either with human ultralente (UL) or NPH insulins. After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH, 50% of patients were randomly assigned to begin insulin lispro or continue on RHI. At baseline, few pretreated patients had LSA (0-4%) and approximately 10% had ISA, whereas 41-45% of patients with IDDM and 23-27% of patients with NIDDM had CRA (IDDM vs. NIDDM, P < 0.001). Within studies, no significant differences were noted over time in ISA, LSA, or CRA attributable to the type of short-acting insulin. When data were pooled, inconsistent changes were noted in ISA and LSA (LSA were greater in NIDDM vs. IDDM at baseline, P = 0.001, and ISA were greater in IDDM vs. NIDDM at 6 months, P = 0.007). Significant levels of CRA were more common in IDDM at all times (P < 0.001, P = 0.022, and P = 0.002 at baseline, 6 months, and 12 months, respectively). For patients receiving insulin lispro, no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study (became positive, remained positive, became negative, or remained negative). IDDM patients were more likely to develop or maintain CRA levels (P = 0.008 vs. NIDDM), whereas antibody levels were comparable among positive individuals. No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients.

Effects of gastrointestinal hormonal peptides on the transformation of human peripheral lymphocytes.

The gastrointestinal peptides secretin and cholecystokinin were found to inhibit the incorporation of 3H-thymidine in the lymphocyte transformation reaction in response to phytohemagglutinin. Both peptides inhibited lymphocyte activation in a dose responsive fashion. This inhibition was not due to the toxicity of these substances, as the lymphocytes remained intact and capable of excluding trypan blue. Neither glucagon nor gastrin had any effects of lymphocyte transformation.

Spectrophotometric enzymatic assay for S-3-hydroxyisobutyrate.

An enzymatic spectrophotometric end-point assay has been developed for determination of S-3-hydroxyisobutyrate in biological fluids. The assay measures NADH production at 340 nm after initiation of the reaction with rabbit liver 3-hydroxyisobutyrate dehydrogenase (EC 1.1.1.31). The assay is not affected by R-3-hydroxyisobutyrate, lactate, malate, 3-hydroxybutyrate, 2-methyl-3-hydroxybutyrate, 3-hydroxyisovalerate, 3-hydroxy-n-valerate, 2-methyl-3-hydroxy-valerate, and 3-hydroxypropionate. The assay does measure 2-ethyl-3-hydroxypropionate, a minor metabolite produced by catabolism of alloisoleucine. Application of the method to measure S-3-hydroxyisobutyrate in plasma obtained from normal, 48-h starved, and mildly and severely diabetic rats gave levels of 28, 42, 112, and 155 microM, respectively.

Juvenile nasopharyngeal angiofibroma in a static population: the implications of misdiagnosis.

We present a 20-year review of juvenile angiofibroma in the relatively static population of Northern Ireland. Seventeen cases were identified and new slides were prepared from the stored paraffin blocks of all their original biopsy material, and re-examined. Five females, a 36-year-old and an 18-year-old male had their diagnoses revised. We suggest clinical criteria, which in conjunction with radiological investigations, should be strictly applied in all cases. Such application would, in retrospect, have identified those cases excluded by pathological re-examination, thus avoiding unnecessary surgery and radiotherapy. Atypical cases which do not satisfy the clinical criteria may be subjected to repeat biopsy but routine initial biopsy is not recommended.

12-Lipoxygenase activity in human uterine cervix.

Homogenates prepared from sections of human uterine cervix or endometrium were incubated with [1-14C]arachidonate and the products examined by radio-TLC. A major product chromatographing with 12-hydroxyeicosatetraenoic acid (12-HETE), and a number of more polar metabolites which were unaffected by 50 microM indomethacin but decreased to the same extent as 12-HETE by 50 microM nordihydroguaiaretic acid, were demonstrated by this technique. The addition of glutathione to the incubation mixture increased the production of 12-HETE, with a proportional decrease in the polar products. There was a large variation in 12-lipoxygenase activity measured in different cervix samples. The levels of the enzyme in the cervix were similar in two groups of uterine samples classified by the histological appearance of the endometrium as proliferative and secretory. However activity was significantly lower in samples taken from post-menopausal patients compared with pre-menopausal patients.

Biochemical studies on a 12-lipoxygenase in human uterine cervix.

Human uterine cervix possesses a high 12-lipoxygenase activity; this enzyme has been isolated in a purified form from the squamous epithelial region of human cervix and its major properties have been investigated. Enzyme activity was present in all subcellular fractions obtained by centrifugation; the highest specific activity was associated with the microsome fraction (160,000 X g pellet). Purification of the enzyme was achieved by acetone precipitation, ion exchange chromatography on CM-cellulose and affinity chromatography on linoleyl-aminoethyl-Sepharose. The product from the incubation of sodium [1-14C]arachidonate with crude enzyme extracts co-chromatographed with authentic 12-hydroxyeicosatetraenoic acid, but the purified enzyme gave a product that behaved like the 12-hydroperoxy derivative. The enzyme had optimum activity at pH 6.5, a Km of 15 microM for arachidonic acid and was stimulated by ATP and Ca2+. Enzyme activity was inhibited by esculetin, nordihydroguaiaretic acid, eicosatetraynoic acid, detergents at concentrations greater than 0.1% (w/v) and preincubation of substrate with GSH and GSH peroxidase. The occurrence of a high 12-lipoxygenase activity is discussed in relation to the specific physiological functions of this tissue.

The effect of acetylsalicylate on aggregation and arachidonate metabolism by human platelets suspended in plasma or buffer.

Acetylsalicylate inhibits prostaglandin and thromboxane production by human platelets suspended in plasma or buffer. Acetylsalicylate inhibits arachidonate-induced aggregation of human platelets suspended in plasma, but the effect of acetylsalicylate on arachidonate-induced aggregation of human washed platelets in buffer has not been reported. We have therefore studied this in relation to arachidonate metabolism in human platelets suspended in plasma or buffer. Platelets suspended in plasma and in buffer were both prepared from each donor, who had not taken acetylsalicylate or like-acting drugs for at least 7 days. Acetylsalicylate was 1500 times less potent in inhibiting arachidonate-induced aggregation in buffer (IC50 = 27.3 +/- 7.5 (s.e.m.)mM) than it was in plasma (IC50 = 18.3 +/- 6.0 microM); whereas it was only 4 times less potent in inhibiting thromboxane production in buffer (IC50 = 110 +/- 51.0 microM) than in plasma (IC50 = 25.3 +/- 8.9 microM). The acetylsalicylate concentration required to inhibit aggregation in buffer was sufficient to inhibit 12-hydroxyeicosatetraenoic acid production whereas the concentration that inhibited thromboxane production in buffer was not. These results indicate that arachidonate-induced aggregation of platelets in buffer may depend on product(s) of lipoxygenase rather than of cyclooxygenase, and is hence insensitive to inhibition by acetylsalicylate compared with arachidonate-induced aggregation of platelets in plasma.

The therapeutic efficacy of human insulin (recombinant DNA) in patients with insulin-dependent diabetes mellitus: a comparative study with purified porcine insulin.

The therapeutic efficacy of human insulin (recombinant DNA) was compared with that of purified porcine insulin (PPI) in seven male subjects with previously treated insulin-dependent diabetes mellitus. In a random crossover design the patients received either PPI or human insulin during one of two consecutive 7-day periods of intensive insulin therapy. Control was evaluated on days 6 and 13. Tissue sensitivity and responsiveness to the study insulins were determined by insulin dose-response studies performed using the euglycemic glucose clamp on days 7 and 14. Insulin dose and all measures of control on days 6 and 13 were not statistically different between treatments. When the insulin dose-response studies during each treatment were compared there were no differences between them. Thus, in previously treated patients with insulin-dependent diabetes, undergoing brief but intensive insulin therapy with continuous subcutaneous insulin infusion, human insulin is as clinically efficacious as PPI. Furthermore, insulin sensitivity and responsiveness, as assessed by dose-response studies during the euglycemic glucose clamp were equivalent for both insulins.