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Biomedical subjects

A Klein

Publications and source records attributed to A Klein.

At least 523 records · Page 29Linked to original sources

A new immunomodulating compound (AS-101) with potential therapeutic application.

There has been interest in the potential of synthetic compounds to modify immune responses by imitation of cytokine action. Direct administration of interleukin 2 (IL-2) in conjunction with adoptive transfer of lymphokine activated killer cells has been used in the treatment of cancer, but there are toxic effects resulting from the high doses of IL-2 required. We have developed a new synthetic compound, ammonium tri-chloro(dioxoethylene-O,O'-)tellurate (AS-101), which has immunomodulating properties and minimal toxicity. The effects of AS-101 on the activation and function of immunocompetent cells have been assessed. We have found that AS-101 induces proliferation and IL-2 production by human lymphocytes in vitro, and enhances the production of IL-2 and colony-stimulating factor by mouse spleen cells. Splenocytes of BALB/c mice injected with AS-101 increased production of IL-2 and CSF in vitro in the presence of mitogen. Mononuclear cells of normal donors acquired responsiveness to recombinant IL-2 and bound monoclonal antibody to IL-2 receptor after incubation with AS-101. Splenocytes of mice treated in vivo with AS-101 expressed high levels of IL-2 receptor. The stimulation of lymphocytes by AS-101 apparently involves an increase in intracellular free calcium. AS-101 administered systemically to mice mediated antitumour effects which could be attributable to its immunomodulatory properties. In addition, AS-101 could directly enhance the ratio of OKT4 to OKT8-positive cells in cultured mononuclear cells from AIDS (acquired immune deficiency syndrome) patients. These results indicate that AS-101 is potentially useful in the treatment of clinical conditions involving immunosuppression.

Adjuvants, Immunologic↗

"Have a piss, drink ogogoro, smoke igbo, but don't take gbana"--hard and soft drugs in Nigeria: a critical comparison of official policies and the view on the street.

One of the consequences of increased exposure to Western influences has been the spread of drug use among Nigerian young people over the last two decades. There is now a buoyant consumer market for home-grown cannabis, and a smaller market for heroin and cocaine within the country. Under successive military regimes, drug use was either downplayed, or regarded as a law enforcement issue. Little work was carried out to gauge the extent of use, or obtain an understanding of the user constituencies. Government policies are entirely informed by Western models and sadly inadequate in understanding Nigerian drug trends and in devising schemes to meet local needs. This article, by giving voice to Nigerian drug users, is an attempt to dispel some misconceptions about drug use and abuse, and to widen the debate surrounding African drug control. There is a grave danger of the war on drugs being exported to African countries where civil societies are weakest in withstanding the onslaught of government and international agencies. This article is therefore an ethnographic drugs study engaging with crucial development issues.

Cocaine-Related Disorders↗

Recurrent, progressive giant cell hepatitis in two consecutive liver allografts in a middle-aged woman.

In this report, we present a 41-year-old woman who developed rapidly progressive "giant cell hepatitis" that lead to end-stage liver disease. She underwent a successful liver transplantation in 1989. However, the giant cell hepatitis recurred in the allograft, resulting in cirrhosis within 4 years. She underwent a second liver transplantation in 1993. After 2 years of a relatively stable course, she again developed cirrhosis and was awaiting liver transplantation at the time of this report. The histopathologic features in the two allografts were identical to her original disease. Despite extensive investigations, no etiology for her liver disease could be found.

Adult↗

Transcription rates and transcript stabilities of macronuclear genes in vegetative Euplotes crassus cells.

In hypotrichous ciliates such as Euplotes crassus genes in the transcriptionally active macronucleus are present on individual minichromosomes which occur in gene-specific copy numbers. This different degree of gene amplification can be understood as a means to preset the expression potential of the respective genetic information. In addition, the actual steady state transcript amounts are governed by the transcription rates and transcript stabilities. To establish the relative effects of these three parameters the copy numbers of genes transcribed by the three different polymerases were determined. The transcript levels of growing or starving vegetative cells were then determined, and nuclear run-on assays were performed to determine the transcription rates of the genes in the different nutritional states. A weak correlation between the gene copy numbers and transcription rates was found. The transcripts of genes synthesized by RNA polymerase II exhibited different stabilities upon starvation of the cells, compared to the supposedly stable ribosomal 5S and 26S RNA. Refeeding of the cells after starvation also resulted in a differential response with respect to the accumulation of the transcripts of different genes transcribed by RNA polymerase II, which can be interpreted in the context of the gene functions.

Animals↗

GW420867X administered to HIV-1-infected patients alone and in combination with lamivudine and zidovudine.

PURPOSE: GW420867X is a nonnucleoside inhibitor of HIV-1 reverse transcriptase. The primary objective was to assess the safety of GW420867X in HIV-1-infected patients. The secondary objectives were to assess the effect of GW420867X on plasma HIV-1 RNA and viral genotype and phenotype and to examine the pharmacokinetics of GW420867X in HIV-1-infected patients. METHOD: HIV-1-infected patients were randomized to GW420867X 50 mg/day, 100 mg/day, or 200 mg/day from days 1-28 (n = 15 per group). Lamivudine (3TC) plus zidovudine (ZDV) was added from days 8-28. A control group (n = 15) received GW420867X, 3TC, and ZDV placebos. RESULTS: Plasma HIV-1 RNA and CD4+ counts improved in the GW420867X groups at days 8 and 28. No significant development of drug resistance was detected. Median observed peak GW420867X concentration (C(max)) generally occurred at 2 hours. The area under the curve over the dosing interval (AUCtau)on day 14 increased less than proportionally to dose, suggesting there was increased clearance and/or decreased absorption. Mean trough GW420867X concentrations were many fold above the in vitro IC(50) in the presence of human serum proteins. Seven of 15 patients on 50 mg GW420867X, 8/15 on 100 mg GW420867X, 12/15 on 200 mg GW420867X, and 8/15 on placebo reported drug-related adverse events. CONCLUSION: GW420867X was well tolerated and has potent antiretroviral activity alone and in combination with 3TC plus ZDV.

Adult↗

[Changes in platelet concentrates from dogs due to storage. I. Platelet count in in vitro function].

The possibility of storage of canine platelet concentrates (PC) was investigated using PC from dogs which were obtained with an automatic cell separator in C4-cell separation sets with low gasdiffusionable Polyvinylchlorid (PVC) storage containers or in C4L-sets developed for storage with high gasdiffusionable Polyolefin (PO) containers, respectively. The storage was carried out for a period of 10 days under permanent agitation at 22 degrees C (C4/22 degrees C, n = 10; C4L/22 degrees C, n = 11) or at 4 degrees C (C4L/4 degrees C, n = 6), respectively. Measurements were done directly after production of the PC, after 6 hours and then daily during the 10-day storage period. In the first part of this paper the results of platelet count (determined automatically with a blood cell differentiation automat and visually), the number of platelet aggregates, the mean platelet volume (MPV) as well as the platelet function with regard to the platelet aggregation induced by collagen or ADP and the resonance-thrombogram (RTG) are presented. The platelet count, measured automatically as well as visually, remained preponderantly constant over the complete storage time in all storage conditions. Dependent on the storage conditions--especially under storage at 22 degrees C--an increase of the number of platelet aggregates and a decrease of MPV was determined. In addition, the loss of platelet function measured by aggregation induced by collagen as well as by ADP showed a significant dependency of storage conditions. The stored platelets lost their ability to aggregate under C4/22 degrees C-conditions after a storage period of 2 days, under C4L/22 degrees C-conditions after 4 days and under C4L/4 degrees C-conditions not before 8 days of storage. Previous resuspending of platelets in fresh plasma delayed the loss of platelet function. Because the loss of platelet function described in the RTG became significant at nearly the same point in time, a storage of canine PC under corresponding conditions can be recommended for upto 2 days (C4/22 degrees C), for 4 days (C4L/22 degrees C) or 8-10 days (C4L/4 degrees C), respectively.

Adenosine Diphosphate↗

[Modulatory effects of polyamines and GABA on rat ileal motility in vitro].

AIM: The aim of our work was to determine the effects of polyamines and GABA on rat ileum motility in vitro. METHODS: Longitudinal strips dissected from control ileum or ileum without myenteric plexus after benzalkonium chloride (BAC) treatment were placed in organ bath chambers. RESULTS: Spermine significantly inhibited spontaneous activity and nerve stimulation-induced response. Inhibition of spontaneous activity was not altered by BAC treatment or tetrodotoxin but was antagonized by BAY K 8644, a L-type calcium channel agonist. Spermine inhibitory effect on nerve-stimulation induced response disappeared after BAC treatment. GABA enhanced the response induced by nerve stimulation but did not antagonize spermine effects; its action was inhibited in presence of atropine and was mimicked by baclofen, a GABAB agonist. CONCLUSION: Polyamines and GABA can modulate rat ileum motility in vitro. GABA acted via neural GABAB receptors. We demonstrate for the first time that spermine exerts a dual action through different mechanisms on both smooth muscle cells and probably intramural neurons.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

[Lethal child abuse (through the use of physical force) in the German Democratic Republic during the period 1 January 1985 to 2 October 1990. Results of a multicenter study].

UNLABELLED: No reliable data are available on cases of lethal child abuse (by active force) in the area of the former German Democratic Republic. In a multicenter study we therefore examined the police and court records for such cases occurring in the period 1 January 1985 to 2 October 1990 in the entire area of the former German Democratic Republic. RESULTS: The study center received information on 39 cases of lethal child abuse which correspond to approximately 7 cases per year. However, a low percentage of undetected crimes which cannot be determined more precisely has to be taken into consideration. Almost 40% of the victims were younger than 1 year, 73% of the victims showed indications of repeated ill-treatment. The effects caused by using direct blunt forces, against the head in particular, were by far the most frequent causes of death. The male contact person (the victim's father, brother or stepfather as well as the life companion of the child's mother in particular) killed the child in most of the cases. As far as it is known, 37% of the male/female offenders suffered from chronic alcoholism; 32% of the male/female offenders were under the influence of alcohol when the crime happened. 83% of the male/female offenders who were found guilty made a confession shortly after the crime had happened or during the interrogations. Almost all the male/female offenders were sentenced to prison (the duration of the imprisonment varied between one year and for life). Due to the considerably lower section rate compared to the one in the German Democratic Republic, it is to fear that each second fatal child abuse is not detected in the new federal states.

Adolescent↗

Recurrent viral associated hemophagocytic syndrome in a child with Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) with subsequent viral-associated hemophagocytic syndrome (VAHS) or secondary hemophagocytic lymphohistiocytosis (HLH) is extremely rare. A 15-month-old girl with disseminated LCH experienced three episodes of VAHS during maintenance therapy. Viral infection, with influenza A, herpes simplex, and adenovirus, respectively, was documented at each episode. She recovered each time after interruption of maintenance therapy. The occurrence of fever and pancytopenia in patients with chemotherapy-treated LCH can be associated with VAHS and not with relapsing LCH.

Adenoviruses, Human↗

[Fatal child neglect in East Germany 1 January 1985 to 2 October 1990. Results of a multicenter study].

UNLABELLED: No reliable data are available on cases of lethal child neglect in the area of the former German Democratic Republic. In a multicenter study we therefore examined the police and court records for such cases occurring in the period 1 January 1985 to 2 October 1990 in the entire area of the former German Democratic Republic. RESULTS: A total of 9 cases were reported to the study center. This does not include undetected cases, whose number, though indeterminate, is probably small due to the general obligation to perform autopsies on all children dying before their 16 birthday. Just over half of all victims were less than one year old, the oldest was 3 1/2 years old. Starvation and severe dehydration were by far the most common causes of death; in half of cases these occurred in combination with hypothermia. Most often mother killed their children by neglect, either alone or together with the victim's father. In the majority of cases no close bond existed between the parents and the child. Seventy percent of the perpetrators were chronic alcoholics. All 10 of the perpetrators were sentenced to imprisonment for periods ranging from one year to life long. Mitigating circumstances were presented at the sentencing phase of the trial on behalf of 20% of those convicted. The experience of legal medical and pathological institutes in the former German Democratic Republic underscores the need to perform an autopsy on all deceased infants and young children. Only this can ensure that no cases of lethal child neglect are overlooked.

Cause of Death↗

Effects of estrogen on vein grafts.

The effect of estrogen on veins was evaluated in vitro and in vivo in three species. 17 beta-estradiol did not significantly alter 3H-thymidine uptake in vitro in segments from either canine femoral or human saphenous veins. In vivo in a rabbit carotid vein graft model, 17 beta-estradiol administration did not affect the development of intimal hyperplasia but was associated with a higher rate of graft thrombosis. These data suggest that the effects of estrogen on veins differs from the effects reported in arteries. These differences were seen both in vitro in veins taken from their normal location and in vivo in veins placed in the arterial circulation.

Adult↗

Physical restraint, informed consent and the child patient.

Parent's expressed, informed consent should be obtained before physical restraining devices are used on the child patient, in the course of dental treatment. Implied consent does not apply to any procedure not normally expected by an average, reasonable person; these procedures include the use of premedicating agents, the use of nitrous oxide sedation, or the use of physical restraint. It is a good, preventive idea to use a well-written general consent form. A specific consent form, clearly labelled, provides a strong defense in court for the dentist.

Child↗