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Biomedical subjects

J M Cummins

Publications and source records attributed to J M Cummins.

At least 55 records · Page 3Linked to original sources
PubMed1993

Treatment of six patients with chronic active HCV hepatitis, with low dose natural human interferon alpha administered orally.

Following the widely accepted therapeutic standard of treatment of HCV infection with parenteral interferon alpha, and encouraged by the author's won good experience with orally administered natural human interferon alpha in low doses (leuHuIFN alpha (ldou)), applied to chronic active HBV hepatitis patients, this form of interferon was given to six randomly selected HCV infected patients (2 women, 4 men) aged 34-62 years. The diagnosis was made based on a clinical and histological evaluation and confirmed by anti-HCV antibodies detection. In 2 out of 6 patients, leuHuIFN alpha (ldou) was employed immediately after steroid discontinuation. Patients were instructed to take one lozenge daily, in the morning, on an empty stomach, and keep it in the mouth until fully dissolved. Observation period varies from 19 to 69 weeks. In 3 patients the therapy concluded, after 19, 61 and 62 weeks, respectively. One patient after 4 weeks of treatment reported increasingly troublesome small joints pain and swelling, which forced leuHuIFN alpha (ldou) discontinuation after 19 weeks. In no patient transaminases normalization was seen during treatment; biochemical and clinical remission after the drug discontinuation was observed in only one patient, in whom the treatment was interrupted due to articular adverse symptoms. With HCV RNA levels assessment being unavailable at the moment, the treatment impact on the virus replication remains difficult to evaluate objectively. The treatment was well tolerated. All patients stressed significant increase of drive and appetite as well as improvement of the exercise tolerance.

Administration, Oral↗
PubMed1992

Low-dose oral natural human interferon-alpha in 29 patients with HIV-1 infection: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate clinical efficacy and toxicity of low-dose oral natural human interferon-alpha (nHuIFN alpha) on CD4+ lymphocyte counts and clinical symptoms in patients with HIV-1 infection. DESIGN: Double-blind, randomized, placebo-controlled trial with crossover. SETTING: Private practice specializing in the treatment of patients with AIDS. PATIENTS, PARTICIPANTS: Only patients with HIV-1 infection and CD4+ lymphocyte counts between 200 and 500 x 10(6)/l were included for study. Thirty out of thirty-one patients at study entry completed treatment with placebo, and 29 completed nHuIFN alpha treatment. Mean patient age was 36 years (range, 25-58 years). The 30 patients included 26 men, of whom 22 were homosexual, and four women; five were drug users and none were currently on zidovudine therapy, although three had been previously. INTERVENTIONS: Patients were randomly assigned to cohorts of 10 to receive either 200 IU nHuIFN alpha once daily orally absorbed or placebo with crossover after 6 weeks. MAIN OUTCOME MEASURES: Every 2 weeks, a detailed history, physical examination, and laboratory tests, including CD4+ and CD8+ lymphocyte counts, were conducted. RESULTS: There was only a slight, transient increase in mean CD4+ lymphocyte counts after 4 weeks of treatment with nHuIFN alpha, compared with a slight decline when placebo was administered. This effect reached statistical significance in a subgroup of patients only and was not sustained after 6 weeks. There were no significant changes in weight and clinical symptoms. All patients remained HIV-1-antibody-positive. Treatment-related adverse reactions were not observed. CONCLUSIONS: Our double-blind, randomized, placebo-controlled clinical trial did not confirm a previous report of efficiency of oral nHuIFN alpha. Although non-toxic, our data do not justify the widespread use of low-dose oral nHuIFN alpha in HIV-infected patients outside controlled clinical trials.

Administration, Oral↗
PubMed1991

Evaluation of luteal support therapy in a randomized controlled study within a gamete intrafallopian transfer program.

A randomized controlled study of luteal support therapy (using intramuscular injections of progesterone and/or human chorionic gonadotropin) was conducted in a trial designed to minimize variables that might adversely affect the change of pregnancy. After applying rigid selection criteria, 207 women were recruited into one of four groups. Mathematical modeling was applied to the results to determine if there were degrees of improvement in uterine receptivity relative to various grades of embryo quality ("E" factor). Although the trial size was insufficient to enable the detection of significant improvements in the pregnancy rates that ranged from 27.5% for non-treatment to 41.2% for those receiving combined treatment, the birth rates were significantly better with luteal support (11.8% versus 29.4%). Similarly, the overall implantation rate just failed to reach statistical significance for luteal support, but the ongoing implantations were significantly better (3.6% versus 9.0%). Data modeling indicated that luteal support, particularly with the combined regimen, could improve the ongoing implantation rate by up to 2.5-fold when the E factor was poorest.

Adult↗
PubMed1990

Transcervical tubal embryo-stage transfer (TC-TEST).

Ultrasound-guided transcervical tubal cannulation (TC-TEST) was used to replace embryos to the fallopian tubes in 17 women whose fallopian tubes were inaccessible by the abdominal route but where at least one tube was shown to be freely patent on a preliminary hysterosalpingogram investigation. In two further cases, the fallopian tubes proved impossible to cannulate, and along with two instances where difficulty was experienced, a common underlying feature was an arcuate or septate configuration of the uterus. Three pregnancies ensued (17%) in cases where the procedure was free of difficulty and the transfers were demonstrably intratubal: two went to term and the third resulted in an ectopic pregnancy. The procedure has so far not shown a benefit over conventional IVF-ET and probably should be avoided in women with any type of tubal disorder.

Adult↗
PubMed1990

Influence of pentoxifylline in severe male factor infertility.

Two in vitro fertilization sperm preparation protocols using pentoxifylline (long and short exposure before insemination) were studied in 57 couples (61 cycles) with male factor infertility. For each cycle, oocytes were divided into two groups for insemination using either pentoxifylline-treated or control semen. Fertilization rates improved over controls in the short protocol (P less than 0.001) and fewer couples experienced fertilization failure (P = 0.02). Sixteen pregnancies ensued (30% per collection with the short protocol), and 4 were from cases with less than 1.0 X 10(6) progressively motile sperm count per milliliter, 1 being as low as 0.2 X 10(6) progressively motile count per milliliter. Seventeen healthy infants have now delivered and pregnancy wastage is not increased. Pentoxifylline is thus a useful sperm treatment for cases of male factor infertility.

Clinical Trials as Topic↗
PubMed1990

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)

Animals↗
PubMed1990

Serum copper, zinc, calcium and phosphorus concentrations of calves stressed by bovine respiratory disease and infectious bovine rhinotracheitis.

The relationship between serum minerals and stress and(or) disease has not been fully evaluated in beef cattle. Two trials were conducted to determine the changes in serum Cu and Zn during market-transit stress and(or) disease. Two additional trials were conducted to determine the changes in serum Cu and Zn after inoculation with infectious bovine rhinotracheitis virus (IBRV), with one of the trials determining the changes in serum Ca and P. Trials 1 (n = 80) and 2 (n = 100) utilized calves that were handled through a normal market-transit system and transported 1,967 km to the feedlot. Trials 3 (n = 37) and 4 (n = 8) used calves that were sero-negative to IBRV and then challenged with 2.7 x 10(5) plaque-forming units of the virus. Serum samples were collected at specified intervals and serum minerals were measured for each trial. Serum Zn for morbid or IBRV-challenged calves was decreased by 34, 57, 29 and 15% (P less than .05) for the four trials, respectively, at peak morbidity. Serum Cu of morbid or IBRV-challenged calves increased 5, 15, 40 and 33% for the four trials, respectively, at peak morbidity. Feed intakes were lower during morbidity for market-transit trials and after IBRV inoculation. Lower feed intake could partially explain the decrease in serum Zn; however, when feed intake was held constant, serum Zn concentration still decreased. Serum Zn decreased and serum Cu increased during market-transit morbidity or after IBRV.

Animals↗
PubMed1990

Treatment of rotavirus infection in neonate and weanling pigs using natural human interferon alpha.

Colostrum-deprived neonate piglets challenged with rotavirus and 3-week-old newly weaned piglets naturally exposed to rotavirus were treated with low doses of natural human interferon alpha (nHuIFN alpha) administered into the oral cavity or included in the liquid diet. The colostrum-deprived piglets given the highest dosage of nHuIFN alpha (50 IU/kg body weight) had lower viral excretion scores at 3 (p less than 0.11) and 4 days (p less than 0.001) after virus inoculation. Average group weights and weight gains were consistently greater for all nHuIFN alpha-treated neonate groups; however, these differences were not significant. Mortality rates were lower in neonates for the three highest nHuIFN alpha treatment groups (20%, 30%, and 20%) than in the lowest treatment group and controls (60% and 45%, respectively). Three-week-old weanling piglets did not have significant differences in the total average diarrhea or rotavirus excretion scores. After 10 days, the group receiving the highest dosage of nHuIFN alpha had significantly greater average weight gain than the control group (p less than 0.05). There was a significant (p less than 0.01) dose-dependent effect between the logarithm10 of the nHuIFN alpha dosage and weight gain in weanling piglets. There were no death losses in the 3-week-old weanling piglets from natural rotavirus exposure.

Animals↗
PubMed1990

Effects of human alpha interferon on experimentally induced equine herpesvirus-1 infection in horses.

The immunotherapeutic effect of low-dose human alpha interferon on viral shedding and clinical disease was evaluated in horses inoculated with equine herpesvirus-1 (EHV-1). Eighteen clinically healthy weanling horses, 5 to 7 months old, were allotted to 3 equal groups. Two groups were treated orally with human alpha-2a interferon (0.22 or 2.2 U/kg of body weight), on days 2 and 1 before inoculation with EHV-1, the day of inoculation, and again on postinoculation day 1. The horses of the remaining group were given a placebo orally on the same days. The horses were monitored daily for changes in body temperature and for clinical signs of respiratory tract disease. Blood and nasal swab specimens were collected daily for virus isolation. Blood was also collected at intervals throughout the monitoring period for evaluation of CBC, serum IgG and IgM concentrations, and antibody titers to EHV-1. Febrile responses, nasal discharge, viral shedding, changes in CBC, and an increase in antibody titers to EHV-1 were noticed in all horses after inoculation. There was no significant difference (P greater than 0.05) in mean values of the factors measured between treatment and control groups.

Animals↗
PubMed1990

Low dose oral alpha-interferon therapy for patients seropositive for human immunodeficiency virus type-1 (HIV-1).

Thirty eight symptomatic and two asymptomatic patients seropositive for human immunodeficiency virus type-1 (HIV-1) were treated with a natural human interferon alpha (HuIFN alpha). Patients were given 2 IU/kg HuIFN alpha orally once daily in powdered maltose held in the mouth to promote mucosal absorption. This oral immunomodulating HuIFN alpha therapy resulted in an increase in CD4+ lymphocytes, an increase in weight, and a dramatic alleviation of clinical symptoms related to HIV-1 infection.

Administration, Oral↗
PubMed1990

Chronic recurrent aphthous stomatitis: oral treatment with low-dose interferon alpha.

Recombinant human interferon alfa-2a (HuIFN alpha) was administered orally once daily in a low concentration (1,200 IU/day) to nine patients with chronic recurrent aphthous stomatitis (RAS), and a placebo solution was given to 10 control chronic RAS patients in a double-blind study. All HuIFN alpha-treated patients had total remission of their aphthae within a 2-week period, while placebo control patients had no change in their condition. The 10 placebo control patients were then treated with HuIFN alpha in a manner identical to that used for the initial principal group. Within a 2-week period, all original placebo patients had complete remission of their aphthae. Eleven of the patients did not have a recurrence of RAS during a subsequent 6-month observation period. Eight patients had recurring aphthae; however, the lesions were resolved by retreating with oral HuIFN alpha for less than 1 week.

Administration, Oral↗
PubMed1990

The history of interferon and its use in animal therapy.

The history of the discovery and development of knowledge on interferon is reviewed in some depth. Although interferons have been considered a very exciting group of proteins for many years during which they were initially shown to have antiviral effects and lately immunomodulatory and immunoregulatory effects, attempts to use them in the therapy of animal and human disease have been disappointing. The initial problem was to obtain sufficient quantities of purified interferons for use in clinical trials. This was overcome in the 1980's by the use of biotechnological techniques which resulted in the synthesis of adequate amounts of interferons. While beneficial aspects of interferon therapy have been shown in a variety of experiments, both in animals and humans, the great potential for interferon treatment has yet to be achieved. In the body, interferon is produced in such small quantities as compared to the large quantities which have been normally used in therapy and it is well recognized that these proteins, the interferons, are particularly potent. A small group of scientists working from biological principles, originating from U.S.A. and are now being developed in Kenya, have found powerful beneficial effects when relatively low dose of IFN-alpha is applied orally to animals and humans, particularly for the treatment of AIDS and East Coast fever. It is now known that interferons are only a part of the cytokine network and indirect and direct effects of interferon can occur on cells to change their behaviour. Many of these effects are non-specific and have a general effect on the course of diseases which, hopefully, can be translated into effective broad spectrum therapy, for man and animals.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Chronic major aphthous stomatitis: oral treatment with low-dose alpha-interferon.

Two patients with chronic major aphthous stomatitis of at least 3 years duration were treated with single daily oral doses (1,200 IU) of interferon alfa-2 alpha (HuIFN alpha). Both patients responded with complete remission of aphthae within 6 weeks. One patient had no recurrence of the disease during a 6-month observation period. The second patient had a recurrent aphtha approximately 4 weeks after the initial lesion resolved; however, the recurrent lesion was less severe than the patient had historically experienced. Retreatment of the recurrent lesion with HuIFN alpha resulted in complete remission within 1 week, and there were no further recurrences during the 6-month observational period.

Adult↗
PubMed1989

Ultrastructural observations on gamete interactions using micromanipulated mouse oocytes.

Cumulus-free mouse oocytes were subjected to zona opening by cracking with microhooks (ZC) or acid drilling (ZD) and fixed 30-90 min after insemination (10(5) pre-capacitated motile sperms/ml). Ultrastructural observations were made on serially thin-sectioned oocytes: 15 ZC and 12 ZD. The zona lesion in ZC oocytes was a clean cut, whereas in ZD oocytes it formed a patchy area of partial zona loss, with reduced microvillar height on the underlying oocyte surface. Spermatozoa were observed within the perivitelline space and partially fusing with the oocyte after 30 min in both situations. Only acrosome-reacted sperm heads were observed to fuse: acrosome intact forms were generally in contact with the zona pellucida, either with the inner or outer surface. Acrosome-intact spermatozoa were also observed deeply embedded in the zona matrix, possibly indicating surface enzyme activity preceding the membrane fusion events of the acrosome reaction proper. The observations are consistent with the need for spermatozoa to make contact preferentially with the zona pellucida during the course of the acrosome reaction.

Acrosome↗
PubMed1989

Pituitary down-regulation using leuprolide for the intensive ovulation management of poor prognosis patients having in vitro fertilization (IVF)-related treatments.

A review of 118 treatment cycles in 115 women under prolonged GnRH analogue (GnRHa; leuprolide) treatment is presented. Patients were selected for treatment primarily on the grounds of poor previous response to stimulation (n = 40), advanced age (greater than 35 years; n = 29), previous premature luteinizing hormone (LH) surge (n = 30), polycystic ovarian disease (PCO; n = 12), and elevated androgens without evidence of PCO (n = 5). An overall pregnancy rate of 28.8% per treatment cycle was attained, compared with a pregnancy rate of 6.2% (6/97, of which none went to term) in the previous completed treatment cycle for the same patients. Ovarian response, as measured by oocytes recovered and maximum estradiol levels observed, was significantly improved in all groups and this was associated with a prolonged follicular phase, significantly more human menopausal gonadotropin (hMG) stimulation and a relatively high incidence of ovarian hyperstimulation, particularly in pregnant patients. Of specific techniques in the GnRHa cycle, GIFT produced a pregnancy rate per treatment of 50% (10/20); IVF-ET, 22% (8/36); PROST, 28% (13/46); and TEST, 19% (3/16). No cycles were abandoned, compared with a cancellation rate of 24% in previous cycles without GnRHa. Patients with PCO performed particularly well on GnRHa management, with a pregnancy rate per treatment of 58% (7/12). Pregnancy rates per treatment for the other groups were as follows: elevated age, 27% (9/33), high androgens, 40% (2/5); premature LH surges, 32% (9/28); and poor responders, 17.5% (7/40).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Neutralizing antibody responses to bluetongue and epizootic hemorrhagic disease virus serotypes in beef cattle.

Blood samples were obtained from sentinel beef cattle at monthly intervals, and the sera were tested for antibodies, using a bluetongue virus (BTV) immunodiffusion test (IDT) and virus-neutralization test (VNT), for 5 BTV serotypes (2, 10, 11, 13, and 17) and 2 epizootic hemorrhagic disease virus (EHDV) serotypes (1 and 2). The cattle tested were transported from Tennessee to Texas in 1984 and 1985. All cattle were seronegative by the BTV IDT at the initial bleeding in Texas in 1984 and 1985. In 1984, 16 of 40 (40%) cattle seroconverted as assessed by results of the BTV IDT. In the 16 seropositive cattle in 1984, neutralizing antibodies were detected to BTV serotypes 10 (n = 7), 11 (n = 3), and 17 (n = 11), and EHDV serotypes 1 (n = 1) and 2 (n = 7). In 1984, no cattle seroconverted to BTV-2 or BTV-13. In 1985, 10 of 36 (27.8%) cattle seroconverted as assessed by results of the IDT. Of the 10 seropositive cattle in 1985, neutralizing antibodies were detected to BTV serotypes 10 (n = 10), 11 (n = 10), 13 (n = 7), and 17 (n = 5), and EHDV serotypes 1 (n = 1) and 2 (n = 7). In 1985, no cattle seroconverted to BTV-2. Clinical diseases attributable to BTV or EHDV was not detected in these cattle in 1984 or 1985.

Animals↗