Biomedical subjects

J R Black

Publications and source records attributed to J R Black.

At least 19 recordsLinked to original sources

PubMed2000

Reduced toxicity with gradual initiation of trimethoprim-sulfamethoxazole as primary prophylaxis for Pneumocystis carinii pneumonia: AIDS Clinical Trials Group 268.

Trimethoprim-sulfamethoxazole (TMP/SMX) is recognized as the superior agent for Pneumocystis carinii pneumonia (PCP) prophylaxis but a high incidence of adverse drug reactions, which may be due to toxic drug metabolites, limits its use. AIDS Clinical Trials Group protocol 268 was a randomized, double-blind, controlled two-arm trial designed to determine whether gradual initiation of TMP/SMX suspension reduced the incidence of treatment-limiting adverse drug reactions compared with routine initiation of double-strength (DS; 160 mg/800 mg) tablets. In all, 372 HIV-1-infected study subjects with a CD4+ cell count <250 x 10 cells/mm3 who had not previously received TMP/SMX for PCP prophylaxis were randomized to receive either daily TMP/SMX DS tablets or a gradually increasing dose of TMP/SMX suspension. The suspension dose was increased to reach the equivalent of a DS tablet by study day 13. During the first 2 weeks, study subjects also received a matching placebo tablet/suspension. After week 2, all study subjects received TMP/SMX tablets for the next 10 weeks. There were significantly fewer study subjects who discontinued prophylaxis during the first 12 weeks when TMP/SMX therapy was initiated gradually (17%) than when initiated in DS tablet formulation (33%) (p =.0002). Gradual initiation was also associated with significantly fewer adverse drug reactions. Gradual initiation of TMP/SMX for primary PCP prophylaxis reduces the incidence of its treatment-limiting adverse effects.

AIDS-Related Opportunistic Infections↗

PubMed2000

Parents' predicted transmitting abilities are not associated with culling prior to second lactation of Michigan, USA dairy cows.

The objective of this study was to test the association between parents' predicted transmitting abilities (PTAs) for milk, fat and protein and subsequent culling of heifers during rearing or first lactation. The data from 1992 to 1996 consisted of the culling outcome of 5619 Michigan Holstein heifers during rearing or first lactation, and the heifers' parents' PTAs from the period in which the heifers were born. Fixed-effect probit models (both dichotomous and ordered) estimated the relationships between culling and parents' PTAs. Herd effect was modeled as a fixed-effect. There was no association between PTAs of milk, fat, and protein for each heifer's parents and subsequent culling of the heifer during rearing or first lactation. Weak evidence for the necessity of modeling the herd effect as fixed was present. The lack of association between parents' PTAs and reason-specific culling (voluntary versus involuntary)--coupled with the counter-intuitive effects of parents' PTAs on the probability of being culled for each of the reasons--raised questions about the utility of classifying culling reasons according to the voluntary nature of the culling decision. We concluded that Michigan producers are not using parents' genetics in heifer-culling decisions.

Animal Husbandry↗

PubMed2000

Grazing methods and stocking rates for direct-seeded alfalfa pastures: I. Plant productivity and animal performance.

A 4-yr study was conducted to determine the effects of two grazing methods (GM) at two stocking rates (SR) on alfalfa pasture plant productivity and animal performance and to ascertain the effect of grazing systems on subsequent performance of steers fed a high-concentrate diet. Eight pasture plots (.76 ha) were seeded in 1988 with alfalfa (Medicago sativa L. var. WL225) and divided into two blocks of four pastures each. Grazing methods consisted of a traditional four-paddock or an intensive 13-paddock system. Pastures were managed to allow a 36-d rest period with an average grazing season of 110 d. The low and high SR were 5.9 vs 11.7, 5.3 vs 10.5, 5.3 vs 7.9, and 5.3 vs 7.9 steers/ha for years 1989 to 1992, respectively. Following the grazing season, steers were placed in a feedlot and fed a high-concentrate diet (81% high-moisture corn, 14% corn silage, 5% protein-mineral supplement) for an average of 211 d. There was no effect of GM on herbage mass, pasture phase ADG, or live weight gain/hectare. Increasing the number of paddocks was beneficial when herbage mass was limited and stocking rate was above 7.9 steers/ha. Increasing SR above 7.9 steers/ha decreased herbage mass and pasture-phase ADG. As forage allowance increased, pasture-phase ADG increased quadratically (R2 = .82, P < .001), reached a plateau, and then decreased. Previous grazing system did not influence the performance of steers in the feedlot or their carcass characteristics. Optimum SR is dependent on herbage mass produced.

Animal Husbandry↗

PubMed2000

Grazing methods and stocking rates for direct-seeded alfalfa pastures: III. Economics of alternative stocking rates for alfalfa pastures.

A framework that permits estimation of economically optimal stocking rates for alternative economic parameters and alfalfa forage allowance was developed and applied to a controlled grazing experiment conducted with Holstein steers (243 kg) placed on direct-seeded alfalfa pastures in central Michigan. Responses of ADG to alternative levels of forage allowance (FA) were summarized by a quadratic function and the associated gains/hectare were calculated. The standard stocking rate (SSR; standard livestock units/ha) that maximized gain/hectare increased with FA and was greater than that which maximized ADG. Net returns to fixed resources(NRFR)/hectare were calculated for alternative SSR and economically optimal SSR were identified under various levels of herbage mass (kg/d). The SSR that maximized NRFR were between the SSR that maximized ADG and gain/hectare. Magnitude of the sale price discount for heavier calves, the slide, influenced the optimal SSR and the sensitivity of net return to SSR. The economically optimal SSR increased as the slide increased because animals stocked under higher SSR weighed less off pasture and therefore received a lower price discount.

Animal Husbandry↗

PubMed1999

Escalating multiple-dose safety and tolerance study of oral WR 6026 in HIV-infected subjects: AIDS clinical trials group 173.

WR 6026 is an 8-aminoquinoline with activity against Pneumocystis carinii in vitro and in an animal model of P. carinii pneumonia that has predicted the clinical utility of related compounds. This study was conducted to assess the safety and tolerance of WR 6026 given once daily for 21 days to HIV-infected subjects with CD4 counts <500 cells/microl. This double-blind, placebo-controlled study employed WR 6026 doses starting at 30 mg once daily and increasing to 60, 90, 120, or 150 mg once daily. Weekly visits for clinical and laboratory monitoring were conducted. Forty-nine study subjects, including 25 subjects with CD4 counts <200 cells/microl and 12 subjects with CD4 counts <100 cells/microl, entered the study. The maximum tolerated dose was 120 mg/day. Dose-limiting methemoglobinemia (>20%) was seen in 3 of 6 study subjects who received 150 mg/day for > or =19 days. Methemoglobin level was correlated with peak plasma WR 6026 concentrations. Three other study subjects developed skin rashes that may have been drug-related, and two developed asymptomatic serum triglyceride levels >1000 mg/dl. We conclude that WR 6026 is well tolerated at doses up to 120 mg/day for 21 days in HIV-infected volunteers including those with CD4 counts <200 cells/microl. Methemoglobinemia appears to be the primary dose-limiting toxicity.

AIDS-Related Opportunistic Infections↗

PubMed1999

Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

In a prospective, randomized, double-blind trial, 149 patients with advanced human immunodeficiency virus (HIV) infection were randomized to receive itraconazole capsules (200 mg daily) and 146 to receive a matched placebo. Both groups were monitored for evidence of fungal infections. Baseline characteristics of the two groups were similar. Failure of prophylaxis occurred in 29 (19%) of the itraconazole recipients and 42 (29%) of the placebo recipients (P = .004; log-rank test). There were 6 invasive fungal infections in the itraconazole group (4, histoplasmosis; 1, cryptococcosis; 1, aspergillosis) and 19 in the placebo group (10, histoplasmosis; 8, cryptococcosis; 1, aspergillosis) (P = .0007; log-rank test). Itraconazole significantly delayed time to onset of histoplasmosis (P = .03; log-rank test) and cryptococcosis (P = .0005; log-rank test). Prophylaxis failure due to recurrent or refractory mucosal candidiasis occurred with similar frequency in the two groups (itraconazole, 15%; placebo, 16%). A survival benefit was not demonstrated. Itraconazole generally was well tolerated. Primary prophylaxis with itraconazole capsules prevents histoplasmosis and cryptococcosis in patients with HIV infection.

AIDS-Related Opportunistic Infections↗

PubMed1999

A comparison of profitability and economic efficiencies between management-intensive grazing and conventionally managed dairies in Michigan.

A retrospective cohort study was designed to determine differences in profitability, asset efficiency, operating efficiency, and labor efficiency between Michigan dairy farms implementing management-intensive grazing (MIG) and conventionally managed dairy farms. Financial information and labor use data for the calendar year 1994 were collected with surveys and personal interviews from 35 MIG dairies and 18 conventionally managed dairies. Because the geographic distribution of MIG and conventionally managed farms in this study did not include Michigan's "dairy belt," extrapolation of these results to an average Michigan or Midwest dairy should be made with care. Within the areas represented, however, multivariate linear regression indicated that MIG dairies had more economic profit than conventionally managed dairies. They captured this profit by being more efficient in asset use, operating practices, and labor use. These results suggest that MIG could provide a sustainable alternate management tool for portions of Michigan's dairy industry.

Analysis of Variance↗

PubMed1996

Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group.

OBJECTIVE: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia. DESIGN: A randomized, double-blind study. SETTING: 24 U.S. academic medical centers. PATIENTS: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less. INTERVENTION: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone. MEASUREMENTS: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions. RESULTS: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P=0.2), therapeutic failure (P>0.2), or a complete course of therapy (P>0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P>.02). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P=0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P=0.01). CONCLUSIONS: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

AIDS-Related Opportunistic Infections↗

PubMed1996

Skin disorders of the lower extremity in adults as reported in the current literature.

This article represents a synthesis of the literature from 1960 to the present. The authors refocused their assigned topic from geriatric skin disorders to adult skin disorders. The distinction between adult and nonadult is clearer than the distinction between geriatric and nongeriatric. The topics covered are divided broadly into malignant and nonmalignant entities.

Adult↗

PubMed1995

Comparative X-ray structures of the major binding protein for the immunosuppressant FK506 (tacrolimus) in unliganded form and in complex with FK506 and rapamycin.

FK506 (tacrolimus) is a natural product now approved in the US and Japan for organ transplantation. FK506, in complex with its 12 kDa cytosolic receptor (FKBP12), is a potent agonist of immunosuppression through the inhibition of the phosphatase activity of calcineurin. Rapamycin (sirolimus), which is itself an immunosuppressant by a different mechanism, completes with FK506 for binding to FKBP12 and thereby acts as an antagonist of calcineurin inhibition. We have solved the X-ray structure of unliganded FKBP12 and of FKBP12 in complex with FK506 and with rapamycin; these structures show localized differences in conformation and mobility in those regions of the protein that are known, by site-directed mutagenesis, to be involved in calcineurin inhibition. A comparison of 16 additional X-ray structures of FKBP12 in complex with FKBP12-binding ligands, where those structures were determined from different crystal forms with distinct packing arrangements, lends significance to the observed structural variability and suggests that it represents an intrinsic functional characteristic of the protein. Similar differences have been observed for FKBP12 before, but were considered artifacts of crystal-packing interactions. We suggest that immunosuppressive ligands express their differential effects in part by modulating the conformation of FKBP12, in agreement with mutagenesis experiments on the protein, and not simply through differences in the ligand structures themselves.

Journal Article↗

PubMed1995

Paronychia.

Paronychia is defined most often in terms of inflammation and is classified as congenital, acute-acquired, or chronic-acquired. The cause for acquired paronychia usually is trauma, and middle-aged women are at greatest risk. Chronic paronychia has been associated with numerous occupations where fluids are the common denominator. Mixed infections usually are found in chronic paronychia, including bacteria, fungus, and yeast. Depending upon the type of paronychia and associated organisms, therapy includes footgear considerations, pharmacology measures, and surgical measures.

Acute Disease↗

PubMed1994

A simple method for isolating alpha 2 macroglobulin-cytokine complexes.

There is the need for a simple, effective procedure for separating alpha 2 macroglobulin-cytokine complexes from free cytokine in order that the nature and possible immunological significance of cytokine-binding by alpha 2 macroglobulin (alpha 2-M) might be further investigated. This presentation describes a method which exploits the presence of zinc-binding sites on alpha 2-M which permit the isolation of complexes from other proteins by zinc-affinity chromatography. Furthermore the method may be used in either a column or batch format.

Chromatography, Affinity↗

PubMed1994

Preliminary analysis of multiple crystal forms of the bovine cyclophilin-cyclosporin A complex.

The immunosuppressant cyclosporin-A (CsA) has been crystallized in complex with the bovine form of its major receptor protein cyclophilin (CyP) in three different forms by the hanging-drop vapor diffusion method. A hexagonal crystal form (P6(1)22 or P6(5)22; a = b = 110 A, c = 440 A) diffracts to 4 A resolution. Orthorhombic (P2(1)2(1)2(1) or P2(1)2(1)2; a = 154.3 A, b = 163.3 A, c = 94.7 A), and monoclinic (P2(1); a = 70.0 A, b = 162.5 A, c = 94.7, beta = 100.0 degrees) forms diffract to 2.2 A resolution. Self-rotation function analysis of the orthorhombic and monoclinic forms shows 52 point group local symmetry for both. A previously reported tetragonal crystal form of the complex also shares this local symmetry, suggesting that the observed motif may pre-exist in solution.

Amino Acid Isomerases↗

PubMed1994

Infection prevention in severely myelosuppressed patients: a comparison between ciprofloxacin and a regimen of selective antibiotic modulation of the intestinal flora.

PURPOSE: To study whether oral ciprofloxacin would be as effective in preventing bacterial infections in severely myelosuppressed patients as selective antibiotic modulation of the gut flora with neomycin/polymyxin B sulfate/nalidixic acid (NPN). PATIENTS AND METHODS: One hundred and five patients undergoing allogeneic or autologous bone marrow transplant, or induction therapy for acute leukemia in 1988 and 1989 were studied. Patients were stratified according to the type of therapy, and randomized in a ratio of 2:1 to either oral ciprofloxacin 500 mg BID, or a combination of oral neomycin 250 mg QID, polymyxin-B 100 mg QID, and oral nalidixic acid 1,000 mg BID. Treatment began on admission and continued until the absolute granulocyte count was greater than 500/mm3 for 3 consecutive days. RESULTS: The 96 evaluable patients were evenly distributed over the 3 treatment groups; 63 patients received ciprofloxacin and 33 received NPN. Fever developed in 92% of patients on ciprofloxacin and in 97% of patients on NPN. (P = 0.66), 6.6 +/- 5.8 and 7.2 +/- 5.3 days from the start of prophylaxis, respectively. Twenty-five patients on ciprofloxacin developed 29 microbiologically documented infections, fewer than the 26 infections in the 22 patients on NPN (P = 0.02). Patients on ciprofloxacin had fewer bacteremias (33%) than did the NPN patients (55%) (P = 0.05). Gram-negative bacteremias were very rare (2 cases; no Enterobacteriaceae), but streptococcal bacteremias were frequent in both arms (27 cases). Side effects were not significantly different, but compliance with ciprofloxacin was better. CONCLUSIONS: Ciprofloxacin is at least as effective as the combination of neomycin/polymyxin/nalidixic acid in the prophylaxis of bacterial infections in myelosuppressed patients, and is better tolerated. Additional agents to prevent streptococcal infections are needed.

Adolescent↗

PubMed1994

Clindamycin and primaquine therapy for mild-to-moderate episodes of Pneumocystis carinii pneumonia in patients with AIDS: AIDS Clinical Trials Group 044.

The objective of this prospective, noncomparative study was to assess the safety and efficacy of clindamycin and primaquine therapy for mild-to-moderate pneumocystis pneumonia (defined as a difference of < 40 mm Hg between the alveolar and the arterial oxygen determinations) in patients with AIDS. In the first part of the study, 22 patients were treated with iv clindamycin (900 mg every 8 hours) for the first 10 days, and then their therapy was switched to oral clindamycin (450 mg every 6 hours) for an additional 11 days. In the second part of the study, 38 patients were treated entirely with oral clindamycin (600 mg every 8 hours). All patients were treated with oral primaquine base (30 mg once daily). Fifty-five (92%) of 60 patients responded to the study treatment. Forty-six (77%) of 60 patients completed a full course of therapy. Of the nine patients with treatment-limiting toxic effects, four had only a mild rash. This study indicates that the combination of clindamycin and primaquine is an effective and well-tolerated therapy for mild-to-moderate pneumocystis pneumonia in patients with AIDS. Entirely oral therapy appears to be as effective as initial therapy with iv clindamycin.

AIDS-Related Opportunistic Infections↗

PubMed1993

Nutrient requirements versus supply in the dairy cow: strategies to account for variability.

Dairy producers must overcome substantial challenges to achieve milk outputs > 14,000 kg of milk/yr per cow within the next decade. To obtain high productivity, a more complete comprehension of the dynamics of metabolism, nutrient utilization, and nutrient absorption will enable better prediction of the efficiency of utilization of these nutrients. A better understanding of the dynamics of rumen function and a more accurate prediction of nutrient flow from the rumen are necessary. Grouping strategy and group feeding behavior influence cow productivity and farm profitability. Understanding of the variance of individual cow responses to management practice is critical. Feeding system design and management and diet formulation techniques need to be developed that recognize the dynamic nature of cow physiology and the variability in feedstuffs and cow requirements. These concepts need to be integrated into total farm management and require the use of new computer modeling technologies.

Animal Feed↗

PubMed1993

Successful allogeneic bone marrow transplantation in an adult with aplastic anemia following orthotopic liver transplantation for non-A, non-B, non-C hepatitis.

A 29-year-old male patient presented with acute liver failure from non-A, non-B and non-C hepatitis, necessitating orthotopic liver transplantation. After operation he developed progressive pancytopenia on the basis of aplastic anemia, which was probably hepatitis associated. After therapy with GM-CSF had failed, he underwent allogeneic BMT from his HLA genotypically identical brother following a conditioning regimen of CY 50 mg/kg x 4 and 500 cGy total lymphoid irradiation. He engrafted promptly but transfusion dependency did not resolve until CMV viremia was treated with ganciclovir. The patient is alive and well 2 years after BMT.

Adult↗

PubMed1993

Heel pain in the older patient.

Older Americans are the fastest growing segment of the US population. For this group, mobility is a significant factor in individual well-being. Heel pain is primarily a symptom found in adults, and like most health problems, increased age has a compounding effect on most disease processes. If heel pain becomes the cause of immobility in an older patient, significant consequences may arise. The true prevalence of heel pain in older individuals is not known precisely. The frequency may lie between 12.5% and 15% on the basis of reports in the literature. The scientific basis of these figures, however, is open to question. No one method of organizing heel pain according to a causative agent or condition is accepted universally. A review of the literature, however, reveals that most reporters ultimately include the same elements in whatever schema they use. In general terms, management of heel pain, regardless of the cause, can be organized according to noninvasive to invasive treatment methods. The authors have found the categories of mechanical, pharmacologic, and surgical to be useful. Selection of a therapeutic method is based on the patient's specific physical circumstance and social situation.

Aged↗