Articles on complementary medicine in the mainstream medical literature: an investigation of MEDLINE, 1966 through 1996.

OBJECTIVE: To investigate the growth of interest, if any, in complementary or alternative medicine by the professional scientific community from the number of MEDLINE-listed and clinical trial-type articles for January 1, 1966, through December 31, 1996. METHODS: Systematic literature searches of the MEDLINE database, using the expanded terms "alternative medicine," "traditional medicine," "acupuncture," "homeopathy," and "chiropractic," were conducted in January 1998 to evaluate the number of all articles. The number of clinical trial-type articles on the above was obtained by conducting searches for those indexed as 1 or more of the following publication types: clinical trial; clinical trial phase 1, 2, 3, or 4; controlled clinical trial; metaanalysis; randomized controlled trial; and limited to "human" trials only. RESULTS: Articles indexed as alternative medicine formed a small proportion (0.4%) of the total number of MEDLINE-listed articles throughout the period studied. From 1966 through 1996, the total number of articles listed in MEDLINE rose significantly to a peak of 400000 additions per annum in 1996 (r = 0.97; P<.001). By contrast, the number of articles indexed under alternative medicine rose progressively only from 1972 through 1986 and since then has been relatively stable at around 1500 additions per annum. For this period, the proportion of clinical trial-type alternative medicine articles was low (mean, 2.1% per annum) but increased significantly from 1987 through 1996, reaching around 10% of the total in 1996 (r = 0.79; P<.001). Patterns of growth in the number of publications for individual therapies have varied during the period studied, and clinical trial-type articles form only a small part of any increase. CONCLUSIONS: Interest in and awareness of complementary medicine among orthodox health care professionals has increased in the past 30 years. The increase in the number and proportion of reports of clinical trials indicates an increasing level of original research activity in complementary medicine and suggests a trend toward an evidence-based approach in this discipline. The cumulative number of clinical trial-type articles is small, however, and more high-quality original research in complementary medicine is required.     

The effect of platelet-activating factor on histamine and muscarinic receptor function in guinea pig airways

Platelet-activating factor (PAF) administered i.v. or by aerosol to guinea pigs elicited an increase in airway responsiveness to both acetylcholine and histamine when compared with guinea pigs exposed to the vehicle bovine serum albumin (BSA). After i.v. PAF, the ED100 for acetylcholine and histamine was 5.4 and 3.4 micrograms/kg, respectively, in comparison with 17 and 6 micrograms/kg, respectively, before PAF, representing approximately a 3- and 2-fold increase in responsiveness, respectively. After aerosol PAF (500 micrograms), the ED100 for acetylcholine and histamine was 13 and 7 micrograms/kg, respectively, whereas after aerosolized BSA, the ED100 for acetylcholine and histamine was 23 and 12 micrograms/kg, respectively, representing approximately a 2-fold increase in responsiveness. However, airway smooth muscle obtained from these PAF- or BSA-treated animals did not exhibit any differences in contractile response to histamine or acetylcholine in vitro. Likewise, there were not significant differences in the binding affinity or receptor density between PAF- and BSA-treated tissues with [3H]quinuclidinylbenzilate or [3H]pyrilamine binding, which were used to identify muscarinic and H1-histamine receptors, respectively. Furthermore, histamine and carbachol-induced phosphoinositide hydrolysis was similar in PAF- and BSA-treated tracheal smooth muscle preparations. Thus, PAF induces airway hyperresponsiveness in the guinea pig that is not related to changes in airway smooth muscle or to changes in muscarinic and histamine (H1) receptor density or function.     

Sputum matrix metalloproteases: comparison between chronic obstructive pulmonary disease and asthma

Asthma and chronic obstructive pulmonary disease (COPD) are different conditions with contrasting airway inflammation and parenchymal disease patterns. A number of matrix metalloproteases (MMPs) are implicated in the pathophysiology of COPD and asthma. Different profiles of airway MMPs may, therefore, be expected in asthma and COPD. The present study compared MMP profiles in the airways of non-smokers, non-symptomatic cigarette smokers, and patients with COPD or asthma (n = 15 subjects per group). Induced sputum was assessed for MMP-1, -2, -3, -8 and -9, and tissue inhibitor of metalloproteases (TIMP)-1 by ELISA. Gelatinase activity was determined by zymography. Sputum from COPD patients contained increased levels of MMP-1, -8 and -9 compared with the other groups (2-7-fold, depending upon group). MMP-9 activity was elevated in COPD sputum by 3-12-fold above the other groups. Sputum from COPD patients had 3-fold higher levels of TIMP-1 than samples from asthmatics or controls, but was not different to smokers. FEV1 correlated negatively with MMP-1, -8, -9, MMP-9 activity and TIMP-1, whereas percent neutrophils in sputum correlated positively with MMP-1, -8, -9, TIMP-1 and MMP-9 activity. The MMP profile in COPD differs to that in asthma and cigarette smokers. This may contribute to, or be a marker of, different pathophysiologies of asthma and COPD.     

Retinoic acid is a potent regulator of growth plate chondrogenesis

Vitamin A deficiency and excess both cause abnormalities in mammalian longitudinal bone growth. Because all-trans retinoic acid (RA) is synthesized from vitamin A, we hypothesized that RA regulates growth plate chondrogenesis. Consistent with this hypothesis, a single oral dose of RA reduced the height of the rat proximal tibial growth plate. To determine whether RA acts directly on growth plate, fetal rat metatarsal bones were cultured in the presence of RA. In this system, RA inhibited longitudinal bone growth by three mechanisms: 1) decreased chondrocyte proliferation, (assessed by 3H-thymidine incorporation), particularly in the proliferative zone of the growth plate; 2) decreased matrix synthesis (assessed by 35SO4 incorporation into glycosaminoglycans); and 3) decreased cell hypertrophy (determined histologically). The growth-inhibiting effects of RA were completely reversed by a retinoic acid receptor (RAR) antagonist. In the absence of exogenous RA, this antagonist accelerated bone growth, as did an RA-specific neutralizing antibody, suggesting that endogenous RA negatively regulates growth plate chondrogenesis. We conclude that RA, acting through RARs, negatively regulates longitudinal bone growth by inhibiting growth plate chondrocyte proliferation, chondrocyte hypertrophy, and matrix synthesis.     

Metabolic and hormonal effects of tacrolimus (FK506) or cyclosporin immunosuppression following renal transplantation

Twelve renal transplant recipients randomised to receive immunosuppression with either tacrolimus (FK506) or cyclosporin underwent oral glucose tolerance tests (OGTT) a median of 8 months (range 7-9) after transplantation. Six healthy subjects acted as controls. Compared with the controls, both transplant groups had significantly elevated fasting (p < 0.05 for both groups) and postprandial (p < 0.001 for tacrolimus and p < 0.05 for cyclosporin) blood glucose concentrations. Fasting hyperinsulinaemia was observed in both transplant groups (p < 0.05) relative to the control subjects. Glucose-stimulated plasma immunoreactive insulin concentrations in the tacrolimus-treatment group were significantly higher than in the cyclosporin group (p < 0.05) and the controls (p < 0.001). Postprandial blood alanine concentrations were also significantly elevated in the tacrolimus group compared with both the controls (p < 0.001) and cyclosporin-treated patients (p < 0.001). The raised insulin concentrations with normal or increased blood glucose concentrations after renal transplantation suggests that insulin resistance was more marked in patients receiving tacrolimus-based immunosuppression.     

Two-year comparison of testicular responses to pulsatile gonadotropin-releasing hormone and exogenous gonadotropins from the inception of therapy in men with isolated hypogonadotropic hypogonadism

Men with the complete form of isolated hypogonadotropic hypogonadism (initial mean testes volume less than 4 mL) require 2 or more yr of exogenous gonadotropin therapy combining hCG and human menopausal gonadotropin (hMG) to achieve maximal, but subnormal, testis size and sperm output. To test whether pulsatile GnRH therapy, which more closely mimics normal hormonal stimulation, would accelerate or further augment testicular growth, hasten the onset of sperm production, and/or increase sperm output more than occurs during conventional exogenous gonadotropin therapy, we administered either hCG/hMG or GnRH from the inception of therapy to 2 comparable groups of men with complete IHH (initial testicular volume, less than 4 mL) and compared their testicular responses during the first 2 hr of therapy. Five men were treated with pulsatile GnRH in doses of 143-714 ng/kg every 2 h, sc, while 11 other men received hCG (2000 IU) and hMG (75 IU FSH and 75 IU LH) im 3 times/week. In the GnRH-treated men, the mean plasma total and free testosterone levels during therapy rose to within the normal range, but were significantly lower (P less than 0.01 and P less than 0.02, respectively) than those in the hCG/hMG-treated men. The mean plasma estradiol concentrations during therapy were within the high normal range and were similar in the two groups. The mean plasma FSH levels achieved in the GnRH-treated men were significantly (P less than 0.01) and 1.3- to 3.2-fold higher than those in the hCG/hMG-treated men. The mean testicular size achieved in the GnRH-treated men was not significantly different from that in the hCG/hMG-treated men (P = 0.08); the mean testicular volumes after 2 yr were 4.8- and 4.3-fold the pretreatment values in the GnRH and hCG/hMG groups, respectively. After 12 months of therapy, sperm production had occurred in one man in the GnRH group and in no subject in the hCG/hMG group. After 24 months, two men in the GnRH group and eight men in the hCG/hMG group produced sperm. Thus, 40% of the GnRH-treated men and 80% of the hCG/hMG-treated men (P = NS) produced sperm after 2 yr of therapy. The sperm concentrations in all men were below 5 million/mL and were comparable in the two groups (P = NS). These results suggest that pulsatile sc GnRH therapy for the first 2 yr does not accelerate or enhance testicular growth, hasten the onset of sperm production, or increase sperm output significantly compared to hCG/hMG.     

Chlamydial infection of subcutaneous fimbrial transplants in cynomolgus and rhesus monkeys

Acute infection with Chlamydia trachomatis serotype E was established in monkey fallopian tube fimbriae by subcutaneous implantation. Depending upon monkey species, from eight to 20 implants could be established in each animal. Animals were given estrogen before percutaneous inoculation of the autografts with Chlamydia. Acute inflammatory changes were found in homografts examined in the first week after infection, with chronic inflammatory changes noted thereafter. Chlamydial inclusions were detected within fimbrial epithelial cells up to seven days postinoculation by fluorescent-antibody staining and immunoperoxidase staining with C. trachomatis-specific monoclonal antibody. Organisms were recovered from autografts up to five days after infection. Analysis of serum antibody by microimmunofluorescence revealed that serotype E-specific antibody of both IgM and IgG classes was produced after infection. We conclude that subcutaneously implanted fallopian tube autografts may provide a useful primate model for kinetic studies of chlamydial infection and immunity.