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Biomedical subjects

T Montgomery

Publications and source records attributed to T Montgomery.

At least 19 recordsLinked to original sources

Influence of oscillating dietary crude protein concentration on performance, acid-base balance, and nitrogen excretion of steers.

Decreasing dietary N inputs into beef cattle feeding operations could potentially decrease environmental concerns relating to air and water quality. Previous studies with sheep suggest that oscillating dietary CP concentrations may improve N use efficiency and thereby decrease dietary N requirements. Therefore, two studies were conducted to determine the effects of oscillating dietary CP concentrations on performance, acid-base balance, and manure characteristics of steers fed high-concentrate diets. Steers were fed to a constant backfat thickness in both studies. In the first trial, 92 steers (mean BW = 408 +/- 2.8 kg; four pens/treatment) were fed the following diets: 1) constant 12% CP, 2) constant 14% CP, and 3) 10 and 14% CP oscillated at 2-d intervals. Steer performance and carcass characteristics were measured. In the second trial, 27 steers were individually fed the same three experimental dietary regimens (nine steers/treatment). Animal performance, arterial acid-base balance, plasma metabolites, and fecal characteristics were measured. In both trials, steers fed the 14% CP diet tended (P < 0.10) to have greater ADG and gain:feed than steers fed the 12% CP diet. Steers fed the oscillating CP regimen had intermediate performance. In Trial 1, steers fed the 14% CP diet tended (P = 0.09) to have smaller longissimus area and higher quality grades than steers fed the oscillating CP regimen. Protein retentions (g/d) calculated from NRC (2000) equations were greater (P = 0.04) for steers fed the 14% CP diet than steers fed the 12% CP diet. Steers fed the oscillating CP regimen tended (P = 0.08) to have greater calculated protein retention (g/d) than steers fed the 12% CP diet. Steers fed the 14% CP diet had greater (P < 0.05) calculated urinary N excretion than steers fed the 12% CP or oscillating CP regimens. Venous plasma concentrations of urea N were greater (P < 0.001) in steers fed the 14% CP diet than in steers fed the 12% CP diet; steers fed the oscillating CP regimen were intermediate but fluctuated over days. Based on arterial blood gas concentrations, acid-base balance was not significantly affected by dietary CP regimen. Results of these trials suggest that the CP requirement of steers in these studies was greater than 12% of the diet DM, and/or that the degradable CP requirement was greater than 6.3% of diet DM. However, the effects of oscillating dietary CP were minimal.

Acid-Base Equilibrium↗

A clinical study of 57 children with fetal anticonvulsant syndromes.

BACKGROUND: Anticonvulsants taken in pregnancy are associated with an increased risk of malformations and developmental delay in the children. To evaluate the pattern of abnormalities associated with prenatal anticonvulsant exposure further, we undertook a clinical study of 57 children with fetal anticonvulsant syndromes. METHODS: Fifty two children were ascertained through the Fetal Anticonvulsant Syndrome Association and five were referred to the Aberdeen Medical Genetics Service. Pregnancy and medical history were obtained through a standardised questionnaire and interview and the children were examined. RESULTS: Thirty four (60%) were exposed in utero to valproate alone, four (7%) to carbamazepine alone, four (7%) to phenytoin alone, and 15 (26%) to more than one anticonvulsant. Forty six (81%) reported behavioural problems, 22 (39%) with hyperactivity or poor concentration of whom four (7%) had a diagnosis of attention deficit and hyperactivity disorder. Thirty four (60%) reported two or more autistic features, of whom four had a diagnosis of autism and two of Asperger's syndrome. Forty four (77%) had learning difficulties, 46 (81%) had speech delay, 34 (60%) had gross motor delay, and 24 (42%) had fine motor delay. Nineteen (33%) had glue ear and 40 (70%) had joint laxity involving all sizes of joints. Of 46 who had formal ophthalmic evaluation, 16 (34%) had myopia. CONCLUSIONS: Speech delay, joint laxity, glue ear, and myopia are common in the fetal anticonvulsant syndromes and autistic features and hyperactivity form part of the behavioural phenotype.

Abnormalities, Drug-Induced↗

Random X inactivation in a girl with a balanced t(X;9) and an abnormal phenotype.

X inactivation is the process by which mammalian females achieve dosage compensation by transcriptionally silencing one X chromosome. In chromosomally normal females, this process is random. However, most females with one abnormal X chromosome demonstrate complete skewing of X inactivation, presumably as the result of cell selection. We present a mentally retarded girl with a 46,X,t(X;9)(q28;q12) karyotype. Analysis of this patient's lymphocytes, using late replication banding and methylation assays for the androgen receptor (AR) and fragile X mental retardation (FMR1) genes, did not show the predicted nonrandom X inactivation pattern. Thus, this patient is functionally disomic for Xq28-qter in a proportion of her cells, most likely resulting in her abnormal phenotype. This case demonstrates the utility of correlating X inactivation patterns with phenotype in females with one structurally abnormal X chromosome, and suggests that both cytogenetic and molecular X inactivation studies should be included in the routine study of these individuals.

Child↗

Mutation analysis of LMX1B gene in nail-patella syndrome patients.

Nail-patella syndrome (NPS), a pleiotropic disorder exhibiting autosomal dominant inheritance, has been studied for >100 years. Recent evidence shows that NPS is the result of mutations in the LIM-homeodomain gene LMX1B. To determine whether specific LMX1B mutations are associated with different aspects of the NPS phenotype, we screened a cohort of 41 NPS families for LMX1B mutations. A total of 25 mutations were identified in 37 families. The nature of the mutations supports the hypothesis that NPS is the result of haploinsufficiency for LMX1B. There was no evidence of correlation between aspects of the NPS phenotype and specific mutations.

Animals↗

Disposition of L-732,531, a potent immunosuppressant, in rats and baboons.

L-732,531 is a semi-synthetic analog of the macrolide tacrolimus (Prograf(R)). Like tacrolimus, L-732,531 is a potent immunosuppressant. In this study, its absorption, distribution, metabolism, and excretion were studied in rats and baboons. In rats, its blood and plasma levels were similar, whereas in baboons, its blood levels were, on average, twice as high as those in plasma. This was consistent with the in vitro blood-to-plasma ratio of L-732, 531, which in these two species, as well as in humans, was much lower than that of tacrolimus and showed a minimal concentration dependence. After iv administration to rats, the blood and plasma clearance of L-732,531 decreased from approximately 60 ml/min/kg at 0.2 mg/kg to 30 ml/min/kg when dosed at 1 and 3 mg/kg. After oral administration, plasma area under the concentration vs. time curve (AUC) and maximal plasma concentration (Cmax) increased more than proportionally to the dose. At 1, 5, and 15 mg/kg, plasma AUC was 29, 466, and 2832 ng.hr/ml, respectively, and Cmax was 10, 129, and 304 ng/ml, respectively. Bioavailability, although compromised by nonlinear kinetics, was estimated to be between 8% and 18%. In baboons, the clearance of L-732,531 was lower than that in rats, especially when calculated from blood concentrations (12 ml/min/kg at 0.2 mg/kg and 8 ml/min/kg at 1 mg/kg). After oral dosing, baboon plasma AUC and Cmax were much lower than those in rats, but as in rats, they increased more than proportionally with increasing doses. The bioavailability of L-732,531 in baboons was estimated at 3%, 9%, and 24% when animals were dosed at 5, 15, and 26 mg/kg po, respectively. After oral administration of [3H]L-732,531 at 5 mg/kg, approximately 32% of the radioactivity was recovered in bile and urine of rats, compared with 9% in baboons. High-performance liquid chromatography profiles of rat and baboon plasma, bile, urine, and feces indicated that L-732,531 was metabolized extensively to a complex mixture of products. Some intact parent drug was observed in feces of orally dosed animals, indicating incomplete absorption. In vitro, L-732,531 was metabolized more extensively by baboon liver microsomes than rat or human microsomes. Its metabolism in human liver microsomes was shown to be catalyzed primarily by cytochrome P450 3A isozymes.

Animals↗

Bovine hereditary zinc deficiency: lethal trait A 46.

Bovine hereditary zinc deficiency, also referred to as Adema disease, is an autosomal recessive disorder which results in inadequate amounts of zinc being absorbed from the gastrointestinal tract and leads to a number of clinical abnormalities. Using semen from a homozygous affected bull and obligate heterozygote cows in embryo transfer studies, 7 offspring were obtained. These included 5 affected calves and 1 heterozygous carrier; the seventh calf died within 48 hours of birth undiagnosed. One unaffected, unrelated bull calf was raised as a control. All the calves were raised and maintained under similar management conditions designed to minimize secondary complications that would obscure the clinical and biochemical observations of a zinc deficient state. The first clinical manifestation of zinc deficiency was diarrhea, followed by skin lesions, poliosis, and a decreased ability to sustain a suckle reflex. Trace mineral analysis of plasma blood samples revealed that plasma zinc concentrations of all the calves were normal at birth; however, they gradually declined in affected calves over the course of 3-8 weeks postpartum to below 0.5 ppm. Biochemical analysis of serum samples showed alkaline phosphatase activity consistently paralleled changes in the plasma zinc concentrations. The oral administration of zinc acetate caused a reversal of all clinical, biochemical, and histologic abnormalities in affected calves. The study of these affected calves allows further insight into the biological role of zinc as well as provides an animal model for the continued investigation of the human homologue acrodermatitis enteropathica.

Acrodermatitis↗

Catastrophic failure of a conforming type of total knee replacement: a case report.

A case study is presented to illustrate the concept of femoral component failure secondary to polyethylene wear in a 67 year old man, 13 years after he had conforming type total knee replacements. This case illustrates the theory that this observed problem may be a leading cause of failure in conforming and nonconforming total knee replacements in the future.

Aged↗

Production responses to various doses and ratios of estradiol benzoate and trenbolone acetate implants in steers and heifers.

At each of three locations, 400 steers and an equal number of heifers were randomized to 10 treatment groups. The purpose of the studies was to evaluate the response of feedlot steers and heifers to single implants containing a combination of estradiol benzoate (EB) and trenbolone acetate (TBA) at two different ratios each at three doses. The selected ratios corresponded to 1E2(estradiol-17 beta):5TBA and 1E2:10TBA. The two ratios were each tested at three different EB/TBA doses (1:5 at 20/70, 40/140, and 60 mg/210 mg, 1:10 and 14/100, 28/200, and 42 mg/300 mg). The test groups were compared to those given each of the compounds alone (60 mg of EB or 300 mg of TBA), as well as to groups reimplanted with Synovex S or Synovex H implants and untreated controls. Steers (P < .01) and heifers (P < .05) implanted with the 1:10 E2:TBA implants gained faster and had better feed conversion (FC) than their counterparts given 1:5 E2:TBA over the 140-d trial. The results indicated that both estradiol benzoate and trenbolone acetate contributed to the efficacy of the combination implant. Contour plots of ADG and FC indicate that increasing the amount of EB above approximately 36 and 37 mg does not significantly increase the response of steers. The results of these studies indicate that the 28 EB/200 TBA dose is close to optimal for growth promotion and feed conversion in both heifers and steers. In steers, carcass value was increased (P < .01) in all test groups except the group give TBA only. Despite a slight reduction in marbling score and percentage of Choice carcasses, carcasses of steers treated with either 28 mg of EB/200 mg of TBA or 42 mg of EB/300 mg of TBA were more valuable (P < .05) than carcasses from steers in any of the 1:10 ratio EB/TBA groups. Carcass values for groups reimplanted with Synovex S or Synovex H or implanted with EB alone were not significantly different from those for groups implanted with any dose of the 1:10 EB/TBA ratio.

Anabolic Agents↗

Coping styles, opioid blockade, and cardiovascular response to stress.

We investigated the hypothesis that the effects of Monitoring and Blunting coping styles are mediated in part by endogenous opioids. Mean arterial pressure (MAP) and heart rate (HR) were measured in 39 males before, during, and after a mental arithmetic stressor. Each subject experienced the protocol once under opioid blockade (naltrexone) and once in a placebo condition, in counterbalanced order. Monitoring and Blunting were assessed using the Miller Behavioral Style Scale. High Blunting and high Monitoring were both associated with poorer MAP recovery under opioid blockade than in the placebo condition. Similar effects were noted for Blunting on the measure of HR. These results indicate that the coping styles of Monitoring and Blunting may be associated with enhanced opioid mediation of cardiovascular recovery from stress.

Adaptation, Psychological↗

Phase I AIDS Clinical Trials Group (075) study of adriamycin, bleomycin and vincristine chemotherapy with zidovudine in the treatment of AIDS-related Kaposi's sarcoma.

OBJECTIVE: To determine the toxicity and maximum tolerated dose of doxorubicin (adriamycin) in combination with fixed doses of bleomycin, vincristine (ABV) and zidovudine in patients with advanced AIDS-related Kaposi's sarcoma. PATIENTS AND METHODS: Twenty-six HIV-seropositive men with Kaposi's sarcoma were treated daily with 100 mg zidovudine orally every 4 h, along with combination chemotherapy using bleomycin 10 U/m2 and vincristine 1.4 mg/m2 (maximum, 2 mg) given intravenously in 2-week cycles. In addition, three successive cohorts of eight patients received escalating doses of doxorubicin each beginning with no doxorubicin (level I), doses of 10 mg/m2 (level II), and 15 mg/m2 (level III). RESULTS: The major dose-limiting toxicity experienced with the combination therapy was severe neutropenia in eight patients, four of whom received level III doxorubicin (15 mg/m2). Therefore, 10 mg/m2 of doxorubicin in combination with zidovudine and BV chemotherapy was defined as the maximum tolerated dose. Other dose-limiting toxicities included neuropathy (n = 2), cutaneous toxicity associated with bleomycin (n = 1), and diarrhea (n = 1). Seventeen patients (71%; 95% confidence interval, 46-85) experienced either partial (n = 13) or clinical complete remission (n = 4) to therapy after a median of five cycles (range, 2-9). CONCLUSION: The maximum tolerated dose of doxorubicin is 10 mg/m2 when given in combination with zidovudine and BV chemotherapy. Response rates observed with the combined antiretroviral and chemotherapy regimen are similar to those previously reported with ABV chemotherapy alone.

Acquired Immunodeficiency Syndrome↗

Adriamycin, bleomycin and vincristine chemotherapy with recombinant granulocyte-macrophage colony-stimulating factor in the treatment of AIDS-related Kaposi's sarcoma.

OBJECTIVE: To determine the maximum tolerated dose of granulocyte-macrophage colony-stimulating factor (GM-CSF) that would reduce the severity and duration of neutropenia from combination cytotoxic chemotherapy in the treatment of AIDS-related Kaposi's sarcoma (KS). DESIGN: Phase I, dose escalation. SETTING: Outpatient clinic of a university hospital. PATIENTS: HIV-seropositive patients with advanced KS. INTERVENTIONS: Combination chemotherapy consisting of adriamycin, bleomycin, and vincristine (ABV), with escalating doses of recombinant human GM-CSF (rhGM-CSF). Patients were treated for a median of six cycles (range, between two and seven cycles) of biweekly chemotherapy with GM-CSF administered in divided daily subcutaneous doses on days 2-12. Serum cytokine levels of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured before, during, and after therapy to correlate with response to therapy. RESULTS: A GM-CSF dose of 250 micrograms/m2 was well tolerated, whereas the next dose escalation, of 500 micrograms/m2, was associated with dose-limiting toxicities, including grade 3 fever, fatigue, and diarrhea. GM-CSF produced predictable cyclic increases in granulocytes, allowing for delivery of full-dose chemotherapy on schedule. All patients were HIV-p24-antigen-negative at study entry; no activation of p24 antigenemia was observed after repeat testing. Consistent changes in cytokine levels were not observed. Responses included one complete and three partial responses, and two patients with stable disease parameters. CONCLUSIONS: We conclude that GM-CSF can be administered safely to patients with AIDS-related KS receiving myelosuppressive chemotherapy, resulting in granulocytic response, without up-regulation of HIV p24 antigen levels in serum.

Acquired Immunodeficiency Syndrome↗

Intravenous immunoglobulin in the treatment of human immunodeficiency virus-related thrombocytopenia.

Fourteen patients with sexually transmitted human immunodeficiency virus (HIV)-related immune thrombocytopenia were treated with intravenous gammaglobulin (IVIG). The patients were treated with a uniform program consisting of 1 g/kg of IVIG on day 1 and day 2, followed by 1 g/kg on day 15. Most patients had pretreatment bleeding symptoms, which included petechiae, spontaneous and traumatic ecchymoses, gum bleeding, and epistaxis. Median baseline platelet count was 17,000/mm3 (range 3-61,000/mm3). After the infusion of the IGIV, all patients had a resolution of their bleeding by day 8. The median maximum platelet count achieved with the IGIV was 220,000/mm3 (range 76-426,000/mm3). No patient achieved either a sustained complete or partial remission after the conclusion of the IVIG therapy. Toxicities were minimal with the majority being headache and nausea. In conclusion, patients with sexually transmitted HIV infection and immune thrombocytopenia respond favorably to IVIG. This treatment should be considered as first-line therapy for patients with HIV-related immune thrombocytopenia who require immediate but temporary increase in their platelet count, attributable to symptoms or signs of clinical bleeding or because of the need for an invasive procedure.

Adult↗

The long-term use of zidovudine in patients with severe immune-mediated thrombocytopenia secondary to infection with HIV.

Various treatments for HIV-related thrombocytopenia have been reported. Since etiologies of the thrombocytopenia may differ with regard to risk group treatment outcomes may also vary. We have recently studied the long-term use of zidovudine in individuals with sexually transmitted HIV infection and severe thrombocytopenia. Twenty-five men, median age 34 years (range, 23-51 years), were treated with zidovudine (1000 mg/day) for a median duration of 12 months (range, 2.5- less than 26 months). Nineteen patients (76%) had had episodes of symptomatic bleeding secondary to thrombocytopenia prior to study entry. All patients bleeding symptoms resolved with therapy. Six (24%) achieved a complete response, with normalization of platelet counts, while 11 patients (44%) achieved a partial response, giving an overall response rate of 68%. The median time to partial or complete normalization of platelet counts was 12 weeks (range, 4-62 weeks). Toxicities were minimal during the study period. Only one patient developed an AIDS-defining diagnosis while on therapy. We conclude that patients with sexually transmitted HIV infection and immune thrombocytopenia may need a prolonged period of therapy with zidovudine to achieve a platelet response. Other treatment modalities may be required for the 30% of patients who do not respond to zidovudine.

Adult↗

Intravenous immune globulin use in patients with human immunodeficiency virus-related thrombocytopenia who require dental extraction.

Five patients with human immunodeficiency virus (HIV)-related immune thrombocytopenia who were undergoing dental extraction were treated with intravenous immune globulin (IVIG). All patients received IVIG, 1 gram per kg, the day before the dental extraction and again the day of the dental extraction. Four patients had a previous history of minor clinical bleeding. The median baseline platelet count before extraction was 20 X 10(9) per liter (range 13 to 44). The median peak platelet count was 100 X 10(9) per liter (range 56 to 528) following infusion. This peak response was achieved by day 2 in 3 patients and by days 5 and 7 in 1 patient each. No patients had complications or toxicity from the infusions or perioperative bleeding. No patients required blood product transfusions for the surgical procedure. In conclusion, IVIG infusion should be considered in patients with HIV-related immune thrombocytopenia requiring surgical procedures when a prompt rise in platelet count is desired.

Acquired Immunodeficiency Syndrome↗

Treatment of epidemic Kaposi's sarcoma with combination chemotherapy (vincristine and bleomycin) and zidovudine.

Advanced AIDS-associated Kaposi's sarcoma often requires systemic cytotoxic chemotherapy. Despite high response rates, the majority of the patients die of opportunistic infections (OIs). Effective anti-retroviral agents in combination with cytotoxic chemotherapy may be useful in preventing the development of OIs in addition to increasing the tumor response. Twelve patients with extensive EKS were treated with a non-myelosuppressive drug regimen consisting of bleomycin and vincristine (BV) in combination with the anti-retroviral agent, zidovudine (ZDV). The dose of ZDV was 200 mg orally every four hours (full dose) in eight patients (Group I) or 100 mg orally every four hours (half dose) in four patients (Group II). Toxicity was acceptable with only 3 patients (all from Group I) requiring blood transfusions. ZDV dose reduction due to granulocytopenia was required in 6 patients (5 in Group I and 1 in Group II). Only two patients developed OIs during 27.5 cumulative months of therapy. The overall response rate was 83% in both groups with 4 patients achieving complete remission (CR) and 6 patients acheiving a partial remission (PR). We conclude that a combination of (BV) chemotherapy and ZDV can be used safely with high response rates. Prospective studies of such combination regimens are currently in progress.

Acquired Immunodeficiency Syndrome↗

Interferon-alpha maintenance therapy after cytotoxic chemotherapy for treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma.

A prospective phase I clinical trial with recombinant interferon-alpha-2b as maintenance therapy after cytotoxic chemotherapy was conducted. Twenty-one homosexual and bisexual males with extensive mucocutaneous or visceral epidemic acquired immunodeficiency syndrome (AIDS)-Kaposi's sarcoma (KS) were studied. After a complete response (6 patients) or partial response (15 patients) from chemotherapy consisting of Adriamycin (20 mg/m2), bleomycin (10 U/m2), and vincristine (1.4 mg/m2; 2 mg maximum), patients were given interferon-alpha (IFN-alpha) in an attempt to prolong disease-free survival. Three dose levels of daily IFN-alpha were tested: 5, 10, and 15 million U. The maximum tolerated dose was 10 million units. Dose-limiting toxicities included recurrent grade 3 fatigue, diarrhea, and fever, which resulted in the termination of therapy in eight patients (38%). Hematologic toxicities were infrequent (four patients; 19%). Responses were observed in two patients on IFN-alpha, both at the 10-million-U dose level. The median duration of response on IFN-alpha therapy following chemotherapy was 8 weeks (range, 3-11). We conclude that the duration of IFN-alpha maintenance response following cytotoxic chemotherapy is short with response to residual disease observed in a minority of cases at this dose and schedule. Additional trials of maintenance therapy in patients with advanced AIDS-KS combining antiretroviral agents are in progress.

Acquired Immunodeficiency Syndrome↗