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Biomedical subjects

L S Jacob

Publications and source records attributed to L S Jacob.

15 recordsLinked to original sources
PubMed1998

Role of dentinal carious lesions in the pathogenesis of oral candidiasis in HIV infection.

The authors describe a clinicopathologic study that evaluated whether dentinal carious lesions are colonized by candidal organisms--and if so, whether there is a relationship between dentinal carious lesion colonization and clinical oral candidiasis, or OC, in HIV infection. Using light microscopy, the authors examined 30 extracted teeth with dentinal carious lesions from people in each of two groups: 30 consecutively treated HIV-positive patients and 30 consecutively treated HIV-negative patients. OC was diagnosed only in HIV-positive patients (40 percent). The dentinal carious lesion pattern in both groups was similar in occlusal, root and proximal caries. Candidal colonization of carious dentinal tubules was more frequent in HIV-positive subjects than it was in HIV-negative subjects. This research shows that it may be important to restore dentinal caries in HIV-infected patients to remove a protected niche for candidal organisms.

AIDS-Related Opportunistic Infections↗
PubMed1995

Experimental local therapy of human melanoma with lytic magainin peptides.

Magainin peptides and model amphipathic peptides exhibit antibiotic activity and are also cytolytic for transformed human cells. Here we demonstrate in vitro that MSI-511 (an all-D amino-acid model magainin peptide) and MSI-130 (a margainin analogue) were more lytic for 17 human melanomas than for normal melanocytes. Melanomas established s.c. in athymic nude mice and then injected once with the peptide MSI-511 completely disappeared in 6 out of 9 animals, whereas a control peptide had no effect. Murine skin at the tumor injection site was initially affected, but healed within 2 weeks with minimal scarring. Similarly, accelerated healing was seen in human skin grafted to SCID mice and injected with MSI-511. Our results indicate that lytic magainin peptides can be used for local tumor therapy with minimal long-term damage to normal tissues.

Animals↗
PubMed1993

Anticancer efficacy of Magainin2 and analogue peptides.

Linear helical channel-forming peptides structurally similar to the Xenopus-derived antibiotic, Magainin2-amide, were synthesized. Because activity resides in the physicochemical properties of the peptides, an all-D-amino acid as well as an all-L-amino acid sequence were tested for anticancer activity. In vitro activity against carcinoma cells and in vivo efficacy against four murine ascites tumors were determined. The novel peptides proved to have enhanced potency in vitro and in vivo as compared to the parent compound. The 50% inhibitory concentrations against A549 cells for the all-D, the all-L, and Magainin2 were 6, 10, and 110 micrograms/ml, respectively. All three peptides had activity against P388 leukemia, S180 ascites, and a spontaneous ovarian tumor when injected i.p. Increase in life span of over 100% was produced for the analogues in the latter two models. The maximally effective concentrations for the analogues were 20 to 25 mg/kg while Magainin2 required 50-60 mg/kg for in vivo efficacy. The all-D-amino acid peptide, MSI-238, proved as effective as doxorubicin at a more advanced stage of the ovarian tumor and this activity may be attributed to its resistance to proteolytic degradation. Therefore, this class of amphiphilic alpha-helical cationic peptides has potential in the peritoneal treatment of ovarian cancer.

Amino Acid Sequence↗
PubMed1992

Effects of magainins on ameba and cyst stages of Acanthamoeba polyphaga.

Amebic keratitis produced by Acanthamoeba spp. is an increasingly important ocular infection in extended-use contact lens wearers. Problems associated with the infection are compounded by the lack of effective and well-tolerated chemotherapeutic agents. The magainins, a group of naturally occurring and synthetic membrane-active peptide compounds, have been shown to be active in vitro against a clinical isolate of Acanthamoeba polyphaga. Two magainins tested extensively had minimal inhibitory and minimal amebicidal values of 20 and 25 micrograms/ml for magainin MSI-103 and 25 and 40 micrograms/ml for magainin MSI-94, respectively. Both amebastatic and amebicidal activities are enhanced by combining the magainins with silver nitrate (200 micrograms/ml) and/or other marginally effective antimicrobial agents. These combinations have activity against both trophic and cystic stages in the Acanthamoeba life cycle and have promise as antimicrobial agents in the treatment of amebic keratitis.

Acanthamoeba↗
PubMed1988

Academic-industrial cooperative graduate program in clinical pharmacology.

Because a new level of sophistication among clinical investigators is necessary for the testing of new agents in human subjects, a close integration of basic science, clinical medicine, and pharmaceutical medicine is required. Experts from the Departments of Pharmacology and Medicine at Temple University School of Medicine and Smith Kline and French Laboratories have combined to form a joint training program in clinical pharmacology. This structured graduate program for physicians couples didactic courses with a defined program of independent research, leading to a Master of Science degree in pharmacology. The development of new technologies and the transfer of them from the "bench to the bedside" demands that the clinician have special competence in clinical pharmacology. This unique joint academic-industrial program sets the goals ensuring that this objective is met.

Clinical Trials as Topic↗
PubMed1985

Role of nocturnal acid suppression on the rate of duodenal ulcer healing: clinical dose-range trials with oxmetidine.

These studies represent the first attempt to compare, concurrently, several once or twice daily dosage regimens of an H2-receptor antagonist for ulcer-healing efficacy in the same national population within the same time period, using the same criteria for patient selection, duration of treatment, and end-point. Investigators from 66 centers entered 745 patients, 17-71 years of age, with endoscopically documented uncomplicated duodenal or pyloric channel ulcers, greater than or equal to 0.5 cm in the longest axis. Patients were randomly assigned to six regimens (five oxmetidine, one placebo) and were dosed once (bedtime) or twice (morning and bedtime) daily. Antacid use was restricted. Endoscopy was performed at wk 0 and 2, and at wk 4 in patients not healed at wk 2. Statistical analysis at wk 4 revealed the following healing rates with oxmetidine: 400 mg bid-73.3%; 600 hs-71%; 400 hs-68.6 and 61.6%; 200 mg bid-61.5%; and 200 hs-59.9%. All of the regimens except 200 hs were statistically significantly superior to placebo. The efficacy of the nocturnal 600-mg dose was comparable to that of 400 mg bid and the efficacy of the nocturnal 400-mg dose was comparable to that of 200 mg bid.

Adolescent↗
PubMed1977

Further studies on the action of ultraviolet light on vascular smooth muscle: effect of partial irreversible receptor blockade.

Isolated rabbit thoracic aorta which is pharmacologically contracted will relax when exposed to ultraviolet light. The relaxation is reversible in that the tension is restored when the light source is removed. The purpose of this investigation was to study further the phenomenon of photorelaxation on vascular smooth muscle. Restoration kinetics were examined for two cases: 1) norepinephrine alone 2) norepinephrine plus phenoxylbenzamine. The photo-induced relaxation in the presence of the irreversible blocker phenoxybenzamine produced a more rapid restoration than the photo-induced relaxation in strips contracted with norepinephrine alone. Angiotensin, which is not blocked by phenoxybenzamine, produced no change in the restoration characteristics of a perturbation on the angiotensin-induced contractions. Strips treated with glycerin, a process which removes storage sites for Ca++, are responsive to exogenous administration of Ca++ but demonstrate no photorelaxation. These results lend supportive evidence to the hypothesis that ultraviolet radiation interferes with the drug-receptor complex.

Angiotensin II↗
PubMedDate not supplied

Cefonicid: an overview of clinical studies in the United States.

Cefonicid, an investigational cephalosporin with a half-life just under 5 hr, was studied by more than 100 investigators in the United States. Of 1,060 cefonicid-treated patients for whom the clinical efficacy of the compound could be evaluated, 91.7% were cured or improved; 95% received a single daily dose. Rates of bacteriologic cure were equal for infections due to gram-positive cocci (89.9%) and gram-negative bacilli (93.2%). Overall rates of favorable response to cefonicid therapy, by disease, were 88.4%, urinary tract infections; 91.4%, lower respiratory tract infections; 95.1%, skin and skin-structure infections; and 91.3%, bone and joint infections. Prophylaxis with cefonicid administered 1 hr before surgery was as effective as that with control antibiotic in reducing the incidence of perioperative infection. For 795 patients who received cefonicid or control drug who underwent gynecologic surgery, prosthetic arthroplasty, cesarean section, or intraabdominal surgery, the reduction in incidence of perioperative infections were equivalent. Resistance to cefonicid developed infrequently (1.3%). Overall safety of cefonicid was comparable with that of control agents except for the frequency of occurrence of diarrhea, which was lower among patients who received cefonicid than among those who received a control drug.

Bacterial Infections↗
PubMedDate not supplied

Penetration of cefonicid into human breast milk and various body fluids and tissues.

A new cephalosporin, cefonicid (1 g), was given intramuscularly to 49 patients 1 hr before they were to undergo surgery and to 10 healthy lactating women. The concentration of cefonicid was assayed by disk agar diffusion with the use of Bacillus subtilis as the test organism. Concentrations of cefonicid in tissue and fluid specimens were obtained. The data demonstrate that within 1 hr of intramuscular injection of cefonicid, effective concentrations of cefonicid in serum and tissue for common microbial pathogens were achieved. This finding suggests that cefonicid would be useful for perioperative prophylaxis in surgical patients. Although the concentration of cefonicid in breast milk was low at 1 hr after injection, more information is needed regarding the subsequent secretion of cefonicid before a conclusive statement can be made concerning the danger of sensitization in infants of nursing mothers.

Adult↗
PubMedDate not supplied

Treatment of urinary tract infections in hospitalized patients: a double-blind comparison of cefonicid and cefamandole.

In a randomized double-blind comparison of cefonicid (dose, 1.0 g every 24 hr) and cefmandole (dose, 1.0 g iv every 6 hr), 147 hospitalized patients (105 men, 42 women) with urinary tract infections (UTIs) were assessed. Ninety-one of the men had complicated UTIs. For the 62 cefonicid-treated men, 61 of 62 etiologic pathogens were eliminated. For 17 patients, reinfection with the pretherapy pathogen occurred in the five- to nine-day posttherapy follow-up. Overall cure rate for cefonicid in the treatment of complicated UTIs was 71%. For the 29 cefamandole-treated men, 28 of 29 etiologic pathogens were eliminated. Reinfection occurred in nine patients. Overall cure rate for cefamandole in the treatment of complicated UTIs was 66%. All 14 men (nine receiving cefonicid; five, cefamandole) with uncomplicated infection were cured. For 25 cefonicid-treated women, cure rate was 84%; one of the failures was due to persistence of the pathogen; three were reinfections during follow-up. For 17 cefamandole-treated women, the cure rate was 82%; two of the failures were due to persistence of the pathogen, and one was a reinfection. Similar, minimal adverse reactions occurred with both drugs. Cefonicid is as effective as cefamandole in curing complicated UTIs in men and uncomplicated infections in both sexes. Cefonicid, however, offers the advantage of once-daily therapy.

Adult↗