Biomedical subjects
A B Richards
Publications and source records attributed to A B Richards.
Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies.
This paper contains a review of the history, natural occurrence, human consumption, metabolism, manufacture, and the results of eight standardized animal safety studies using trehalose. Trehalose (alpha,alpha-trehalose) is a naturally occurring sugar containing two D-glucose units in an alpha,alpha-1,1 linkage. Trehalose functions in many organisms as an energy source or a protectant against the effects of freezing or dehydration. It also possesses physical and/or chemical properties that are different than other sugars, which may make trehalose an attractive ingredient in food, health and beauty and pharmaceutical products. Data are presented supporting safe human consumption of trehalose in doses up to 50 g, and the physiologic ability of humans to digest it. No consistent treatment-related, dose-dependent adverse effects were observed in any of the eight safety studies performed at doses up to 10% of the diets. On the basis of these toxicity studies, human studies in which doses of trehalose were administered to various populations, and consumption of trehalose in commercial products in Japan, it is concluded that trehalose is safe for use as an ingredient in consumer products when used in accordance with current Good Manufacturing Practices.
Recognizing and managing your patient's alcohol abuse.
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Treatment of preretinal Valsalva haemorrhages with neodymium:YAG laser.
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Treatment of primary Sjögren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group.
The purpose of this investigation was to examine the safety and efficacy of four dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a 12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times [TID] daily) compared to placebo in subjects with primary Sjögren's syndrome. This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at a dose of 150 IU administered TID by oral lozenge significantly improved stimulated whole saliva output compared to placebo after 12 weeks of treatment. The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. IFN lozenges demonstrated a good safety profile, with no serious adverse events found in any treatment group. There were no significant differences between the placebo and the four doses of IFN for adverse events by total number, organ system, severity, dropouts, and number judged to be related to treatment. In conclusion, these results demonstrated that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary Sjögren's syndrome improved salivary output and decreased complaints of xerostomia without causing significant adverse medical events.
Reduction of morning stiffness and improvement in physical function in fibromyalgia syndrome patients treated sublingually with low doses of human interferon-alpha.
One hundred and twelve fibromyalgia syndrome (FMS) patients were randomized into one of four demographically similar groups (n = 28/group). Sequential primary FMS patient volunteers were to receive daily sublingual placebo or interferon-alpha (IFN-alpha) at 15, 50, or 150 IU. After a screening evaluation, analgesic or sedative hypnotic medications were withdrawn. Two weeks later, daily IFN-alpha or placebo was initiated with follow-up evaluations at 2-week intervals ending with week 6. One primary, three secondary, and seven tertiary variables were assessed. Study outcome was based on improvement in the tender point index (TPI). The TPI did not improve with any IFN-alpha dose. However, significant improvement was seen in morning stiffness and in physical function with the 50 IU IFN-alpha (p < 0.01). None of the other outcome means changed significantly and no adverse events were attributable to IFN-alpha therapy.
Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: effects of low-dose, sublingual use of human interferon-alpha.
A clinical study was designed to utilize flow cytometric immunophenotyping and chromium release from cultured tumor target cells to characterize peripheral blood mononuclear leukocyte (PBML) subpopulations and natural killer activity in healthy normal controls (n = 18) and in patients with fibromyalgia syndrome (FMS) at baseline (n = 124) and again after 6 weeks of treatment with low-doses of orally administered human interferon-alpha (IFN-alpha). Volunteer subjects discontinued all analgesic and sedative hypnotic medications for 2 weeks prior to the baseline phlebotomy. Laboratory measures included a complete blood count; a phenotypic analysis of PBML by flow cytometry; and in vitro natural killer (NK) cell activity. After baseline blood sample collection, the FMS patients were randomized to one of four parallel treatment groups (n = 28/group) to receive sublingual IFN-alpha (15 IU, 50 IU, 150 IU), or placebo every morning for 6 weeks. The tests were repeated at week 6 to evaluate treatment effects. At baseline, FMS patients exhibited fewer lymphocytes and more CD25+ T lymphocytes than did normal controls. By week 6, the main significant and consistent change was a decrease in the HLA-DR+ CD4+ subpopulation in the 15 IU and 150 IU treatment groups. These data do not support an immunologically dysfunctional PBML phenotype among patients with FMS as has been observed in the chronic fatigue syndrome.
Slapped in the face.
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Propriospinal neurons in the C1-C2 spinal segments project to the L5-S1 segments of the rat spinal cord.
Physiological studies indicate that neurons in the upper cervical spinal cord have descending projections to the lumbosacral spinal cord and mediate inhibition of dorsal horn neurons activated from afferent input. In the present study, retrograde tracing techniques were used to examine the distribution of propriospinal neurons in C1-C2 spinal segments that project to lumbosacral spinal segments. Fluorogold or horseradish peroxidase were injected unilaterally or bilaterally into the L5-S1 spinal segments. After 2-4 days, rats were perfused with fixative and C1-C2 spinal segments were processed for retrograde labeling. Numerous neurons were found in the C1-C2 segments. In unilaterally and bilaterally injected rats, retrogradely labeled neurons were located on both the ipsilateral and contralateral sides. Retrogradely labeled neurons were located in the following locations: lateral cervical and spinal nuclei, nucleus proprius, ventral horn and the central gray region (area X). These studies demonstrate a descending projection from C1-C2 segments to the lower lumbar and sacral spinal cord. We hypothesize that many of these C1-C2 propriospinal neurons are important in modulating responses of spinal neurons at lower segmental levels to various peripheral stimuli.
Bilateral orbital fat prolapse in cutis laxa.
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Management of rupture of the posterior urethra.
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Oral treatment of transmissible gastroenteritis with natural human interferon alpha: a field study.
During a natural outbreak of transmissible gastroenteritis (TGE), groups of piglets were treated orally for 4 consecutive days with placebo or 1.0, 10.0 or 20.0 international units (IU) natural human interferon alpha (nHuIFN alpha). Piglets that were 1-12 days of age and given 1.0, 10.0 or 20.0 IU nHuIFN alpha had significantly (P < 0.01) greater survival rates than placebo-treated piglets; survival rates were the greater for the highest level of nHuIFN alpha treatment. In contrast, beneficial effects of nHuIFN alpha were not observed in piglets farrowed during the disease outbreak and given nHuIFN alpha within hours of birth. Oral nHuIFN alpha therapy modulates the natural course of high morbidity and mortality commonly seen with TGE.
Proposal for changes in cystoscopic follow up of patients with bladder cancer and adjuvant intravesical chemotherapy.
A famous surgeon observed that the most important instrument for the management of superficial bladder cancer was a typewriter because it facilitated the organisation of the regular follow up examinations that are so important in controlling this disease. Cystoscopic follow up must be lifelong, and the cost, in the broadest sense, to both patient and health service is considerable. A recent study has suggested that the conventional frequency of bladder examinations may not be necessary and that most patients could be spared many cystoscopies. Instillation of cytotoxic drugs in the bladder has been shown to reduce the recurrence of tumours destroyed endoscopically and the development of new tumours elsewhere in the bladder. Because intravesical instillations are inconvenient, expensive, and may be toxic they have been reserved for patients thought to be at greatest risk of recurrence. However, two clinical trials have shown that a single cytotoxic instillation may be beneficial for low risk patients. If this is verified in everyday practice, the routine use of intravesical chemotherapy for all patients at the time of initial treatment could reduce the need for cystoscopies even further. Such changes should improve the quality of life of the 7000 new patients with superficial bladder cancer each year in England and Wales and allow savings to be made in the NHS.
Intraocular adrenaline maintains mydriasis during cataract surgery.
Cataract surgery is performed more easily if mydriasis can be maintained until the intraocular lens has been inserted. Intraocular irrigation with adrenaline is thought to be of benefit in this respect, and is used by some surgeons but not others. This prospective double blind controlled trial assessed the efficacy and safety of using perioperative adrenaline during extracapsular cataract surgery, as an adjunct to preoperative topical mydriatics. Seventy patients were randomised to receive intraocular irrigation fluid with or without 1:1,000,000 adrenaline. The adrenaline entering the eye through the anterior capsulotomy needle helped to resist the miosis induced by expression of the nucleus (7.1 versus 6.5 mm). The mydriasis maintained during irrigation aspiration was significantly greater in the group receiving adrenaline (6.6 versus 6.0 mm, p < 0.02). Their pupil diameters were also significantly larger at 20 minutes (p < 0.001) and 30 minutes (p < 0.01) into surgery. Pupillary constriction to a diameter of less than 5 mm occurred more frequently in the group not receiving adrenaline. Pulse rate and blood pressure in the 27 patients who had local anaesthesia showed no significant difference between the treatment groups (p > 0.05), and there was no significant variation from baseline (p > 0.05). Intraocular irrigation with adrenaline 1:1,000,000 is a safe and effective means of maintaining mydriasis during cataract surgery.
Oral therapy with human interferon alpha in calves experimentally injected with infectious bovine rhinotracheitis virus.
Fifty-six calves, seronegative for infectious bovine rhinotracheitis (IBR) virus, were randomly divided into 7 equal groups (n = 8) and given 0.0, 0.05, 0.50, or 5.00 international units (IU) of natural or recombinant human interferon alpha per kg body weight (nHuIFN-alpha or rHuIFN-alpha, respectively) orally once daily for 4 consecutive days, starting 2 days before intranasal inoculation with virulent IBR virus. Calves given 0.05 IU nHuIFN-alpha/kg bwt had significantly greater weight gain at days 15 (P < 0.10) and 25 (P < 0.05) than the placebo-treated (0.0 IU) control group. The treatment groups given 0.05 and 0.5 IU nHuIFN-alpha/kg bwt nHuIFN-alpha had fewer days with temperature > 40 degrees C (P < 0.05 and P = 0.10, respectively), and lower mean rectal temperatures on days 8 and 11 (0.05 IU/kg bwt; P < 0.10) or on day 11 (0.5 IU/kg bwt; P < 0.10). None of the calves given 0.05 IU nHuIFN-alpha/kg bwt required antibiotic therapy. Calves given 0.50 IU/kg bwt of nHuIFN-alpha, or 0.05 IU/kg bwt of rHuIFN-alpha had fewer (P < 0.05) total days of antibiotic therapy compared to controls. These data indicate that low dose oral IFN-alpha treatment significantly reduced the clinical effects of IBR virus infection in feedlot cattle in an interferon dose-dependent fashion.
Low-dose orally administered alpha interferon treatment for feline leukemia virus infection.
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Market stress-associated changes in serum complement activity in feeder calves.
Classical hemolytic complement (C) of calves was analyzed during a protocol designed to imitate the usual market handling of feeder calves from the southeastern United States. Serum C concentrations of the calves (n = 100 x 4 years) were evaluated on their farm of origin, on arrival at an auction market, on arrival at a feedyard, and during their first 4 weeks in the feedyard. Complement concentrations (measured in CH50 units) were typically lowest at the farm of origin and highest when the calves entered the auction market 28 to 133 days later. Serum C concentrations decreased after the calves encountered the severe stresses of being in the auction market for 7 days, 24-hour truck transport (1,932 km) to the feedyard, and the first 7 days in the feedyard. The C concentrations recovered after 21 to 28 days in the feedyard. Steers had significantly (P less than or equal to 0.05) lower C concentrations than did heifers in 3 of 4 years at the farm of origin, and in 2 of 4 years at the auction market. Morbid calves had significantly (P less than or equal to 0.05) lower C values than did healthy calves on day 7 in the feedyard in 3 of 4 years. There were significant differences in C concentrations of calves from different farms of origin in each of the 4 years. There was no significant difference in C concentrations of calves that were vaccinated vs those not vaccinated with Pasteurella haemolytica.
Low-dose oral administration of human interferon alpha can control the development of Theileria parva infection in cattle.
Two natural human interferon alpha preparations, (nHuIFN-alpha [Cantell]) and (nHuIFN-alpha [ISI]), were used for the oral treatment of cattle experimentally infected with Theileria parva parva. In the first experiment, 8 Friesian bulls were inoculated with a 1 in 10 dilution of a sporozoite stabilate of T.p. parva (Marikebuni) stock. Four of the cattle were treated daily with 1 international unit/kg body weight (i.u./kg bwt) of nHuIFN-alpha (Cantell) from day -2 to day 8 p.i. None of the 4 calves given IFN developed clinical theileriosis, but 3 of the 4 control calves died of theileriosis while the fourth had a mild infection. Three of 4 treated calves and the 1 surviving control calf developed a detectable antibody response to T.p. parva schizont antigen but, on challenged with a 10-fold higher dose of stabilate, the surviving control animal and only 1 of the 4 treated calves proved to be immune. In a second experiment, 4 groups of 4 calves were inoculated with the same stabilate dilution. Three treatment groups were given either 1 i.u. nHuIFN-alpha (Cantell), 1 i.u. nHuIFN-alpha (ISI), or 10 i.u. nHuIFN-alpha (ISI)/kg bwt from day -2 to day 8 p.i. once daily and the fourth group were controls. Clinical theileriosis occurred in 2 controls, 2 calves given 10 i.u. nHuINF-alpha (ISI), 1 calf given 1 i.u. nHuIFN-alpha (ISI) and no calves given 1 i.u. nHuIFN-alpha (Cantell)/kg bwt. Of these, 2, 1, 0 and 0 cattle died in the respective groups.(ABSTRACT TRUNCATED AT 250 WORDS)