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Biomedical subjects

J D Berman

Publications and source records attributed to J D Berman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Efficacy of a short course (10 days) of high-dose meglumine antimonate with or without interferon-gamma in treating cutaneous leishmaniasis in Guatemala.

Sixty-six Guatemalan men with parasitologically confirmed cutaneous leishmaniasis, due most commonly to Leishmania braziliensis, were randomly assigned to receive one of three treatment regimens: meglumine antimonate (meglumine) for 20 days; meglumine for 10 days; and meglumine for 10 days plus alternate-day injections of interferon-gamma. In each group, meglumine was given intravenously as 20 mg of antimony/(kg of body weight.d). All treatment regimens were associated with similar response rates: the lesions of 19 (90%) of 21 patients who received meglumine for 20 days, 18 (90%) of 20 patients who received meglumine for 10 days, and all 22 patients who received meglumine plus interferon-gamma were completely reepithelialized by 13 weeks. In addition, for patients receiving all treatment regimens, test-of-cure cultures for Leishmania were negative and reactivation of lesions did not occur during 12 months of follow-up. The high efficacy of our 10-day course of meglumine indicates that the currently recommended duration of 20 days may be unnecessary for infections caused by L. braziliensis and suggests that a 10-day course of high-dose antimony should be tested as therapy for cutaneous leishmaniasis in other geographic areas.

Adolescent↗
PubMed1994

Paromomycin resistance in Leishmania tropica: lack of correlation with mutation in the small subunit ribosomal RNA gene.

The aminoglycoside antibiotic paromomycin is a potentially useful anti-leishmanial chemotherapeutic agent. Resistance to this antibiotic was studied using Leishmania tropica. Promastigotes resistant to 210 micrograms/ml of paromomycin were selected by exposing them to gradual increments of this drug. Previous work in Escherichia coli, Tetrahymena, and yeast mitochondrial mutants has demonstrated mutations in the E. coli small subunit ribosomal RNA at the 1409:1491 basepair position, or equivalent positions in other organisms, resulting in basepair disruption. When the nucleotide sequence at both the DNA and RNA levels of the resistant L. tropica promastigotes cultured in the presence of paromomycin was compared with those of the drug-sensitive parent, there was no sequence change at the putative mutation site. Paromomycin resistance in L. tropica is apparently due to other mechanisms.

Animals↗
PubMed1994

Efficacy of 28-day and 40-day regimens of sodium stibogluconate (Pentostam) in the treatment of mucosal leishmaniasis.

The efficacy and toxicity of two regimens of antimony, 28 and 40 days of 20 mg of antimony/kg/day, were compared in the treatment of culture-positive mucosal leishmaniasis involving more than one anatomic site. Forty consecutive eligible Peruvians with infiltrative or ulcerative mucosal disease of the lips, nose, palate-uvula-pharynx, or larynx-epiglottis were randomized to receive either 28 days (P28) or 40 days (P40) of sodium stibogluconate (Pentostam). Treatment was prematurely terminated due to thrombocytopenia in three patients and two patients did not complete six months of follow-up. At one month post-treatment, 13% (2 of 16) of the P28 patients and 16% (3 of 19) of the P40 patients no longer had infiltrates or ulcers and were initially considered cured. During a further 11 months of follow-up, infiltrated lesions healed in eight more P28 patients and in 10 more P40 patients. The cure rate after 12 months of follow-up was therefore 63% for both groups (10 of 16 in the P28 group and 12 of 19 in the P40 group). The total of 13 patients who had infiltrates or ulcers at the 9-12-month follow-up were considered failures. All seven patients (three in the P28 group and four in the P40 group) whose lesions were culture-positive for Leishmania at some point in the 12 months after treatment, and who were thereby parasitologic failures, were also clinical failures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Botulinum toxin inhibits arachidonic acid release associated with acetylcholine release from PC12 cells.

The molecular mechanisms of depolarization-induced calcium-dependent acetylcholine (ACh) release and its inhibition by botulinum neurotoxin type A (BoTx) are not clear. We studied these mechanisms in an in vitro cholinergic neuronal pheochromocytoma PC12 cell line model. Cultured monolayer PC12 cells were differentiated by treatment with 50 ng/ml nerve growth factor (NGF) for 4 days to enhance cellular ACh synthesis and release. Stimulation of these cells with high K+ (80 mM) in the perfusion medium caused a marked increase (three to four times) in [3H]ACh release in a Ca(2+)-dependent manner. K(+)-stimulated [3H]ACh release was totally inhibited by pretreatment of cells with BoTx (2 nM) for 2 h. High K+ also stimulated the release of arachidonic acid ([3H]AA) from the cell membrane, which was inhibited by BoTx (2 nM). Addition of phospholipase A2 (PLA2) inhibitors (quinacrine, 4-bromophenacyl bromide, manoalide) to the perfusion medium inhibited K(+)-stimulated [3H]ACh and [3H]AA release in a dose-dependent manner. Inclusion of exogenous AA, the PLA2 activator melittin, or PLA2 itself prevented the effect of BoTx. These results demonstrate that in NGF-differentiated PC12 cells, AA release is associated with ACh release, BoTx inhibits both processes, and increased AA can protect against BoTx.

Acetophenones↗
PubMed1993

Evaluation of pentamidine for the treatment of cutaneous leishmaniasis in Colombia.

Ninety-two patients in Colombia with cutaneous leishmaniasis were randomly assigned to groups to be treated with meglumine antimonate (infected control subjects; 10 mg of antimony/kg intramuscularly, twice a day for 20 days), pentamidine (2 mg/kg every other day intramuscularly, for a total of seven injections), or itraconazole (200 mg orally, twice a day for 28 days) or to receive no treatment (negative control subjects). In the group treated with meglumine antimonate, 21 of 23 patients healed by the first follow-up visit, 1.5 months after the end of therapy, and did not relapse (91% cure rate). In the pentamidine-treated group, 23 of 24 patients healed and did not relapse (96%). Four of the 23 pentamidine-treated patients who ultimately were cured had terminated therapy prematurely (after receiving 4-6 injections) because of hypotension (2 patients), hypoglycemia (1 patient), or headache and myalgias (1 patient). In a subsequent group of 19 patients who were administered 2 mg of pentamidine/kg every other day for a total of only four injections, 14 healed without relapse (74% cure rate). The itraconazole-treated group was similar to the no-treatment control group in terms of the number of patients for whom therapy failed (75% and 64%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Treatment of Brazilian kala-azar with a short course of amphocil (amphotericin B cholesterol dispersion).

Amphotericin B is an effective but toxic antileishmanial agent. Lipid-encapsulated amphotericin B should have a high therapeutic index for visceral leishmaniasis because reticuloendothelial cells, the sole site in which Leishmania is found, will phagocytize and concentrate the complex. Amphotericin B cholesterol dispersion (Amphocil; 2 mg/[kg.d] intravenously) was administered to 10 Brazilians with kala-azar for 10 days (cohort 1) and to 10 Brazilians with kala-azar for 7 days (cohort 2). All patients were successfully treated: 19 of the 20 patients were without visible parasites in the bone marrow; the mean time to afebrility was 4.2 days; spleen size regressed by a mean of 79% 2 months after therapy; and no patient had clinical or laboratory abnormalities by the end of 6-12 months of follow-up. Side effects were fever and chills accompanied by respiratory distress, but not nephrotoxicity, in children < 3 years of age.

Adolescent↗
PubMed1993

Survivability and infectivity of viscerotropic Leishmania tropica from Operation Desert Storm participants in human blood products maintained under blood bank conditions.

To assess the potential for leishmaniasis being transmitted through blood transfusion, we studied the survival of Leishmania in blood products under blood bank storage conditions. We report that L. tropica- or L. donovani-contaminated transfusable blood products are a risk to the blood supply for at least 25 days postdonation under blood bank general conditions. The blood components that have been implicated are whole blood, packed red blood cells, platelet concentrate, and frozen-deglycerolized red blood cells, but not, as would be expected, fresh frozen plasma. Blood units containing four infected monocytes per milliliter of blood with a mean of three amastigotes per monocyte contain viable parasites for 15 days under blood bank storage conditions. Furthermore, animal studies showed the presence of parasites in the blood of cutaneously infected animals and the possibility of transmitting the disease to healthy experimental animals by blood transfusion from infected animal donors. Three of three BALB/C mice showed metastasis to the lower extremities and face after they received 0.25 ml of blood from a CPDA-1 bag seeded with 1.5 x 10(5) amastigotes per ml of blood kept under blood bank conditions for 30 days. This proves that Leishmania not only survives blood banking procedures and storage conditions but that the parasite retains its infectivity. The results of this study and the recent demonstration of L. tropica-infected monocytes in the blood of a patient returning from Southwest Asia suggests that transfusion-associated leishmaniasis can occur.

Adult↗
PubMed1992

Placebo-controlled clinical trial of sodium stibogluconate (Pentostam) versus ketoconazole for treating cutaneous leishmaniasis in Guatemala.

To determine the relative efficacy and toxicity of stibogluconate and ketoconazole for the treatment of cutaneous leishmaniasis, a comparative trial was conducted in which 120 Guatemalan men with parasitologically proven cutaneous leishmaniasis were randomly divided into three treatment groups: sodium stibogluconate (20 mg of antimony per kilogram per day intravenously for 20 days), ketoconazole (600 mg per day orally for 28 days), and placebo. Treatment outcome was influenced by species. Among patients infected with Leishmania braziliensis, 24 (96%) of 25 in the stibogluconate group but only 7 (30%) of 23 in the ketoconazole group responded. Among Leishmania mexicana-infected patients, only 4 (57%) of 7 in the stibogluconate group but 8 (89%) of 9 in the ketoconazole group responded. These differences emphasize the importance of speciation in the treatment of leishmaniasis.

Administration, Oral↗
PubMed1992

Efficacy of intermittent dosage of 8-aminoquinolines for therapy or prophylaxis of Pneumocystis pneumonia in rats.

Experimental 8-aminoquinolines from Walter Reed Army Institute for Research are effective for prophylaxis or therapy of Pneumocystis carinii pneumonia in rat models. In the present study, primaquine, WR6026, and WR238605 were tested in prophylaxis and treatment models of P. carinii pneumonia to compare the effectiveness of continuous versus intermittent dosing. For treatment of P. carinii pneumonia, the drugs showed detectable effects when given once every 4 days (primaquine and WR6026 at doses greater than 8 mg/kg; WR238605 at doses greater than 2 mg/kg). For prophylaxis, WR6026 and WR238605 were effective given alone daily (WR6026 at doses greater than 0.25 mg/kg; WR238605 at doses greater than 0.57 mg/kg). WR6026 and WR238605 at 4 mg/kg given once every 4 days for prophylaxis were as effective as daily trimethoprim-sulfamethoxazole. These studies suggest that higher doses of 8-aminoquinolines administered at appropriate intervals may be as effective as continuous dosing for prophylaxis of P. carinii pneumonia.

Aminoquinolines↗
PubMed1992

Sodium stibogluconate (Pentostam) overdose during treatment of American cutaneous leishmaniasis.

A 27-year-old woman who acquired cutaneous leishmaniasis in Central America was inadvertently treated with 10 times the intended daily dose of the pentavalent antimonial compound sodium stibogluconate (Pentostam): 8500 mg (143 mg/kg) instead of 850 mg. The patient felt "wiped out" during the 4-h infusion of the drug. After the mistake in dosing was discovered, she was vigorously hydrated and carefully monitored in an intensive care unit for greater than 48 h. Her vital signs were stable, and no arrhythmias were noted. Her alanine aminotransferase level rose briefly to 2.4 times the upper limit of normal, and her white blood cell count briefly fell 43% to a low of 3700/microliter. Her skin lesions subsequently healed without further therapy. Although sodium stibogluconate has been associated with a variety of side effects, in this case, a single high dose of the drug was tolerated without serious toxicity.

Adult↗
PubMed1992

Activity of amphotericin B cholesterol dispersion (Amphocil) in experimental visceral leishmaniasis.

Standard therapy of human visceral leishmaniasis with parenteral pentavalent antimonial agents is generally curative but has the disadvantages of a 28-day treatment course, occasional treatment failures, and toxicity. The antifungal and antileishmanial agent amphotericin B has been complexed with lipids to develop a less toxic formulation of amphotericin B. Because lipid particles are phagocytized by the reticuloendothelial system, lipid-associated amphotericin B should be concentrated in infected macrophages and be very effective against visceral leishmaniasis. One formulation, amphotericin B cholesterol dispersion (ABCD) (Amphocil), was tested for antileishmanial activity in Leishmania donovani-infected hamsters. In the first experiment, hamsters were infected, administered with the drug 3 days later, and then sacrificed after a further 4 days. ABCD (dose needed to suppress 99% of hepatic parasites compared with controls [SD (99)], 0.4 mg/kg of body weight) was 15 times as effective as conventional amphotericin B [SD (99), 6.0 mg/kg]. Pentavalent antimony in the form of meglumine antimonate had an SD (84) of 416 mg/kg. In a second experiment in which animals were allowed to become more heavily infected, the drug was administered 10 days after infection and the animals were sacrificed after a further 2, 7, or 11 days. ABCD was approximately four times as active as conventional amphotericin B. These experiments suggest that ABCD is at least four times as active as conventional amphotericin B against visceral leishmaniasis and that clinical trials are warranted.

Amphotericin B↗
PubMed1992

Recommendations for treating leishmaniasis with sodium stibogluconate (Pentostam) and review of pertinent clinical studies.

Pentavalent antimonial compounds have been the mainstay of the treatment of visceral, cutaneous, and mucosal leishmaniasis for approximately half a century. Pentostam (sodium stibogluconate) is the pentavalent antimonial compound available in the United States (through the Centers for Disease Control). As dosage regimens for treating leishmaniasis have evolved, the daily dose of antimony and the duration of therapy have been progressively increased to combat unresponsiveness to therapy. In the 1980s, the use of 20 mg/kg/day (instead of 10 mg/kg/day) of antimony was recommended, but only to a maximum daily dose of 850 mg. The authors have concluded on the basis of recent efficacy and toxicity data that this 850-mg restriction should be removed; the evidence to date, which is summarized here, suggests that a regimen of 20 mg/kg/day of pentavalent antimony, without an upper limit on the daily dose, is more efficacious and is not substantially more toxic than regimens with lower daily doses. We recommend treating all forms of leishmaniasis with a full 20 mg/kg/day of pentavalent antimony. We treat cutaneous leishmaniasis for 20 days and visceral and mucosal leishmaniasis for 28 days. Our judgment of cure is based on clinical criteria.

Antimony Sodium Gluconate↗
PubMed1991

Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line.

The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG):cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06-0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.

Adenosine Triphosphate↗
PubMed1991

8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models.

Three 8-aminoquinolines from the Walter Reed Army Institute for Research (WRAIR), WR6026, WR238605, and WR242511, strongly inhibited Pneumocystis carinii growth in vitro at 1 microgram/ml. This activity was similar to that of primaquine. In rat therapy models, the WRAIR compounds affected Pneumocystis pneumonia at doses as low as 0.25 mg/kg (WR242511) or 0.5 mg/kg (WR6026 and WR238605). At these doses, primaquine alone was ineffective as therapy. In a rat prophylaxis model, all three WRAIR 8-aminoquinolines were extremely effective at daily doses of 0.57 mg/kg, showing activity greater than that of primaquine at this dosage and comparable to that of trimethoprim-sulfamethoxazole at 50/250 mg/kg.

Aminoquinolines↗
PubMed1991

Pharmacokinetic justification of antiprotozoal therapy. A US perspective.

Infections with parasitic protozoa have always been problems for the developing world and are becoming of greater importance to the developed world in this age of easy international travel. The major human protozoal diseases are summarised with an emphasis on their presentation in normal hosts and in immunocompromised individuals and current US drug treatment recommendations are discussed. Present antiprotozoal regimens are based either on a pharmacokinetic rationale or on clinical trial and error. Regimens based on trial and error include amphotericin B against leishmaniasis and arsenic against African trypanosomiasis. Regimens which are to some extent driven by pharmacokinetic or biochemical considerations include paromomycin and metronidazole against amoebiasis, sodium stibogluconate against leishmaniasis, halofantrine and mefloquine against malaria, dihydrofolate reductase (DHFR) inhibitors against Pneumocystis carinii and toxoplasmosis and aerosolised pentamidine against P. carinii pneumonia. The majority of pharmacokinetic studies have been performed only on agents which have some therapeutic activity against other diseases of the developed world. Despite the trend toward rational treatment regimens, no studies have been performed that permit optimisation of antiprotozoal treatment regimens on the basis of clinical conditions such as renal failure.

Antiprotozoal Agents↗
PubMed1991

Efficacy and toxicity of pentostam against Panamanian mucosal leishmaniasis.

We tested the World Health Organization (WHO) recommended treatment for mucosal leishmaniasis in 16 Panamanians with disease due to Leishmania braziliensis panamensis. Disease was mild in this population because it was limited to the nasal mucosa and only one patient had septal perforation. The patients were administered 20 mg antimony (in the form of Pentostam) per kg intravenously each day for 28 days. Ten patients completed therapy and were cured at 12 month follow-up. Three patients completed therapy, healed their lesions, but relapsed at the six or 12 month follow-up. Three patients terminated therapy prematurely because of liver enzyme elevations in conjunction with either EKG abnormalities or musculoskeletal complaints; none of these patients were healed. This study indicates that in patients with mild mucosal leishmaniasis, the WHO regimen is curative in 77% patients who complete treatment and in 63% of all patients.

Adult↗