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Biomedical subjects

D Schwartz

Publications and source records attributed to D Schwartz.

At least 235 records · Page 13Linked to original sources

An analysis of the determinants of hepatic allograft rejection using stepwise logistic regression.

Hepatic allograft rejection is currently diagnosed using both histologic and clinical criteria. The purpose of this study is to extract data from the allograft biopsy, which can establish the diagnosis of rejection with more precision. A total of 566 allograft biopsies were examined in 56 patients following orthotopic liver transplantation, and 35 variables were examined. Using stepwise logistic regression, only six of these variables affected the diagnosis of rejection. These were portal tract spillover, portal tract eosinophilia, portal vein endothelialitis, portal tract neutrophilia, central vein endothelialitis, and cholestasis. Coefficients of these variables were determined, and could be used to calculate the probability of rejection for a given biopsy. Using this model the probability of having rejection can be calculated using histologic data alone.

Biopsy↗

Aneuploidy with neural tube defects: another reason for complete evaluation in patients with suspected ultrasound anomalies or elevated maternal serum alpha-fetoprotein.

Some recent reports have suggested that invasive testing is unnecessary when ultrasound either confirms or refutes a neural tube defect (NTD). However, counseling for recurrence risks and the possibilities for in utero therapy would be significantly altered by an aneuploid karyotype. We report our experience with 53 pregnancies affected by NTD in which we found 13.2% of these fetuses with abnormal chromosomes. In view of the higher than previously published incidence of aneuploidy, we believe that fetal karyotypes are essential in the evaluation of all fetuses with NTDs.

Aneuploidy↗

A safe, pre-fabricated, immediate postoperative prosthetic limb system for rehabilitation of below-knee amputations.

Thirty-eight below-knee amputees were treated with a commercially available pneumatic prosthetic limb system, applied immediately postoperatively, that would allow immediate weight bearing following lower extremity amputation. Thirty-four limbs were amputated for peripheral vascular insufficiency and four were amputated due to trauma. Weight bearing was initiated an average of 4.7 days following surgery and patients were discharged with a non-removable temporary prosthesis at an average of 8.9 days. Thirty-three healed and were uneventfully fit with standard below-knee prosthetic limbs. Three required revision to the above-knee level. In a controlled setting, early weight bearing in the peripheral vascular insufficiency patient can be initiated with a low risk of local wound complication.

Adult↗

Pharmacological activities of spirogermanium and other structurally related azaspiranes: effects on tumor cell and macrophage functions.

Spirogermanium is a germanium containing azaspirane which has been shown to have activity in experimental models of cancer and immune dysfunction. A series of analogs of the parent compound were synthesized and evaluated in a number of in vitro and in vivo biological assays to define the structure-activity relationships of this class of compounds relative to their potential therapeutic activities. In a colony-forming assay using HT-29 human colon carcinoma cells various analogs in which carbon replaced germanium (e.g. carbon) retained the potent cytotoxic activity in vitro seen with spirogermanium. Increased cytotoxic potency within the group of carbon containing analogs was directly related to increase in the length of the alkyl group(s) attached to the carbon atom opposite the azaspirane ring structure. DNA and protein synthesis by HT-29 cells was inhibited by these compounds. However, inhibition occurred only at supralethal concentrations or after long exposure times with the drug. None of the azaspiranes demonstrated in vivo anti-tumor activity against P388 leukemia or ADJ-PC6 plasmacytoma. The effect of these compounds on macrophage cell function was evaluated in vitro by their ability to modulate superoxide (O2-) production by macrophages. Spirogermanium inhibited the production of O2- by activated macrophages with an IC50 of 5 microM. Although macrophage viability did not appear to be decreased at the respective IC50 concentrations, the rank order potency for the analogs in the O2- production assay was directly proportional to that measured for their cytotoxic potency in the HT-29 colony formation assay. The results demonstrate that, within this class of compounds, (1) potent biological activity does not require the presence of germanium in the structure; (2) in vitro cytotoxic activity does not appear to be a direct result of the inhibition of macromolecular synthesis, and (3) macrophage function can be modulated in vitro at non-cytotoxic concentrations. These results are discussed in context with the reported anti-tumor activity of spirogermanium and the potential anti-arthritic and immunomodulatory activity of this class of compounds.

Animals↗

Septicemia from biliary tract infection.

One hundred four strains of microorganisms were isolated from the blood in 76 episodes of septicemia originating from biliary tract infection. The 70 patients involved included 40 with acute cholecystitis without previous surgery, 17 with cholangitis following previous surgery, and 13 patients with malignant disease, with or without previous surgery. The most common organisms were Escherichia coli, Klebsiella, Streptococcus, and Proteus. Various streptococci, most of them from group D, were involved in 21% of the episodes. Twenty-five patients underwent surgery following the bacteremia. In ten of 12 operations performed shortly after the septicemia, bile culture yielded the same organism(s) as in the blood. The types of organisms in blood, and especially the important role of streptococci, must be taken into consideration when choosing antibiotics for therapy for and prevention of biliary septicemia.

Aged↗

Polymicrobial bacteremia.

Of 585 bacteremic episodes studied prospectively at Rokach Hospital during a 4-year period (1980-1983), 70 (12%) episodes observed in 67 patients were due to multiple species. A total of 170 strains of microorganisms were involved, 2-5 per bacteremic episode: 130 (76%) were aerobic Gram-negative bacilli, 36 (21%) were Gram-positive cocci (most of them streptococci) and 4 isolates (2%) were Candida. The most common sources of infection were the urinary tract (31 episodes), intra-abdominal foci (22 episodes, half of them from biliary tract), and skin or soft tissue infection (14 episodes). At least one organism was also recovered from a local focus of infection in more than 50% of cases. Many patients had severe underlying diseases in addition to old age. People with biliary infection had, however, a relatively lower frequency of underlying disease. Fifty-six percent of the episodes were hospital-acquired, primarily those related to urinary infection with indwelling catheters, intra-abdominal abscess and infected burns. Twenty-eight patients (42%) died as a result of the bacteremia. Polymicrobial bacteremia was found to be quite common in the population studied, and the urinary tract was the most important portal of entry, especially in the older patients.

Aged↗

Hypothalamic infusion of amphetamine increases serotonin, dopamine and norepinephrine.

Microinjections of amphetamine into the lateral hypothalamus are known to cause anorexia and hypodipsia. These effects are thought to be mediated by an action of amphetamine on the catecholaminergic terminals to release dopamine and norepinephrine and block reuptake. Direct evidence of neurochemical release was lacking; therefore microdialysis was used to measure monoamines and their metabolites in the extracellular fluid of the lateral hypothalamus while amphetamine diffused out through the microdialysis probe. Amphetamine infusion significantly increased serotonin, dopamine and norepinephrine; it decreased dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and did not change homovanillic acid (HVA). These results suggest that amphetamine releases dopamine, norepinephrine and serotonin and blocks reuptake which thereby retards neurotransmitter breakdown. The net effect was a quadrupling of extracellular monoamines which could react with postsynaptic receptors. This supports the hypothesis that the behavioral effects of amphetamine injections into the lateral hypothalamus are mediated by dopamine, norepinephrine and suggests, in addition, serotonin.

Amphetamine↗

Ro 15-0216: a nitroimidazole compound active in vitro against human and animal pathogenic African trypanosomes.

In vitro systems for the continuous cultivation of Trypanosoma brucei brucei, T. b. gambiense, T. b. rhodesiense, T. congolense and T. vivax were used to determine the antitrypanosomal activity of the 2-substituted nitroimidazole Ro 15-0216. For all trypanosome species, the concentration which inhibited parasite growth by 50% (IC50 value) was established: 0.0957 microgram ml-1 (T. b. brucei TC221), 0.1327 microgram ml-1 (T. b. gambiense STIB 754-A), 0.0450 microgram ml-1 (T. b. rhodesiense STIB 704-BABA), 0.0896 microgram ml-1 (T. congolense ILNat 3.1) and 0.0109 microgram ml-1 (T. vivax ILRAD 1392). The IC50 value of its major metabolite Ro 19-9638 was 0.0341 microgram ml-1 (T. b. rhodesiense STIB 704-BABA). Furthermore, minimum exposure times required to render T. b. brucei non-infective for mice as well as preventing their growth in vitro have been established to be three, four, six and ten hours at drug concentrations of 30, 10, 3 and 1 microgram ml-1, respectively.

Acetanilides↗

The prognostic value of DNA ploidy combined with histologic substaging for incidental carcinoma of the prostate gland.

Although current methods of histologic substaging for incidental prostatic carcinoma are useful, they offer only general indications of potential tumor behavior. To further define the biologic tendencies of stage A cancers, an examination was made of the role of DNA ploidy combined with histologic staging in archival material selected to achieve both a representative sample and long-term follow-up. With histology alone, 36% of stage A2 cancers and 9% of A1 neoplasms were progressive. Adding DNA flow cytometry to histology resulted in a significant improvement in the capacity of pathologic evaluation to predict outcome. Progression occurred in 67% of aneuploid stage A2 prostate cancers and in none of the nonaneuploid stage A1 tumors. Despite current limitations in the interpretation of DNA histograms from archival tissue, flow cytometry has significant potential in the pathologic evaluation of incidental prostatic carcinomas.

Aged↗

A prospective study of the relation between smoking and fertility.

A prospective study of fertility was conducted from 1977 to 1982. Analysis of the relation between cigarette smoking and occurrence of a pregnancy was performed on 1887 couples. The actuarial pregnancy rate was 82.9% at the end of a year. Cigarette smoking by both members of the couple was found to be related to decreased fertility when this factor was considered alone. But after including all the confounding covariates in a Cox semi-proportional hazards model for survival data, no relationship remained between cigarette smoking and fertility. Odds ratios were respectively 0.86 (95% confidence interval: 0.63, 1.19) and 0.99 (0.85, 1.14) for women smoking and men smoking. This could suggest that the relationship found by other authors might be at least partly explained by a relation between cigarette smoking and other factors related to fertility.

Adult↗

The immune system response to Campylobacter infection.

Campylobacter may be one of the most common causes of bacterial gastroenteritis (GE) in children. It has recently been suggested that it is one of the bacterial pathogens most likely to infect immune-compromised children, and it may facilitate colonization of enteric pathogens. The immune system response was studied in 12 children with Campylobacter fetus subspecies jejuni (CBJ) infections. Serum concentrations of IgA, IgM, and IgG were analyzed using a Beckman auto-analyzer. Sera specific Ab to CBJ were tested with CBJ specific enzyme-linked immunosorbent assay (ELISA). Mitogen stimulation of lymphocytes was performed to three lectins: Con A, PWM, and PHA. The lymphocyte blast transformation to Campylobacter was studied using the Campylobacter antigen. T-cell subsets were studied using the monoclonal antibodies Leu 2, 3, and 4 (Becton Dickinson). Chemotaxis was measured in modified Boyden chambers; chemotactic stimulants were the Formyl Met Leu Phe, Campylobacter antigen virion, and E. coli 0111 B. Immunoglobulins were normal in nine cases and abnormal in two children previously diagnosed as agammaglobulinemic and one diagnosed as hypoagammaglobulinemic. Specific serum Ab level was significantly higher in the CBJ group, except in the agammaglobulinemic group. Stimulation indices to mitogens and monoclonal subset were in the normal range. The blastogenic transformation to CBJ Ag was decreased compared to normal lectins, and positive and high compared to controls. The chemotactic activity to campylobacter Ag was decreased in comparison to other stimulants. Most CBJ infections are self-limiting due to a normal immune response and collaboration of all cellular limbs. When, however, the immune response is disturbed, we may find a prolonged and complicated course of CBJ.

Antibodies↗

Dexfenfluramine and feeding reward.

This review describes background experiments and new findings showing that dexfenfluramine inhibits self-stimulation of a lateral hypothalamic (LH) feeding-reward system. Earlier work suggested that self-stimulation excites a pathway to the ventral tegmental area (VTA), where the mesolimbic dopamine system is involved in self-administration of food and drugs. LH stimulation also excites taste neurons in the nucleus tractus solitarius (NTS). This helps explain why stimulation can induce feeding responses and also reward self-stimulation responses. Stimulation-induced feeding and self-stimulation are modulated by physiological signals that control an animal's appetite and body weight. An animal will self-stimulate at a slower rate after it has just eaten, or if it is overweight, or if it is given an anorectic dose of insulin. At the same time, responses to turn off automatic stimulation tend to increase. Paradoxically, racemic fenfluramine decreased both self-stimulation and stimulation-escape, which suggested overall lethargy, but new results show this can be avoided by using just the d isomer. Dexfenfluramine inhibited LH self-stimulation but not stimulation-escape. It also released serotonin in the LH, as shown by microdialysis. These results suggest that dexfenfluramine can release serotonin that has as one of its effects the inhibition of circuitry for feeding-reward.

Animals↗