Case Report: Thrombotic-Thrombocytopenic Purpura Following Ipilimumab and Nivolumab Combination Immunotherapy for Metastatic Melanoma.

A man in his early 50s presented with small bowel obstruction, requiring emergency laparoscopic small bowel resection for the metastatic melanoma of the jejunum with no identifiable primary lesion. One week after his first treatment with ipilimumab and nivolumab, he presented with diffuse abdominal pain, constipation, and fatigue. A computerized tomography scan did not identify a cause for his symptoms. This was rapidly followed by thrombocytopenia on day 11 and then anemia. He commenced intravenous corticosteroids for a suspected diagnosis of immune-related thrombocytopenia. On day 15, a generalized onset motor seizure occurred, and despite plasmapheresis later that day, the patient died from fatal immune-related thrombotic thrombocytopenic purpura (TTP). This was confirmed with suppressed ADAMTS13 (<5%) testing on day 14. Immune-related TTP is a rare and, in this case, fatal immune- related adverse event. Further studies are required to identify additional immunosuppressive management for immune-related TTP.

Mycobacterium malmoense septic arthritis.

We report a case of septic arthritis of an interphalangeal joint and osteomyelitis of the phalanx due toMycobacterium malmoense in a 61-year-old man with a 20 year history of rheumatoid arthritis treated with steroids and azathioprine. This was successfully treated with ethambutol, rifampicin and clarithromycin. To our knowledge this is the only reported case of septic arthritis due to this pathogen which is usually associated with respiratory disease or cervical lymphadenitis.

Albumin is a major serum survival factor for renal tubular cells and macrophages through scavenging of ROS.

We have previously shown that lysophosphatidic acid (LPA), an abundant serum lipid that binds with high affinity to albumin, is a potent survival factor for mouse proximal tubular cells and peritoneal macrophages. We show here that BSA also has potent survival activity independent of bound lipids. Delipidated BSA (dBSA) protected cells from apoptosis induced by FCS withdrawal at concentrations as low as 1% of that in FCS. dBSA did not activate phosphatidylinositol 3-kinase, implying that its survival activity occurs via a mechanism distinct from that for most cytokines. On the basis of the following evidence, we propose that dBSA inhibits apoptosis by scavenging reactive oxygen species (ROS): 1) FCS withdrawal leads to ROS accumulation that is inhibitable by dBSA; 2) during protection from apoptosis, sulfhydryl and hydroxyl groups of dBSA are oxidized; and 3) chemical blockage of free sulfhydryl groups or preoxidation of dBSA with H(2)O(2) removes its survival activity. Moreover, dBSA confers almost complete protection from cell death in a well-established model of oxidative injury (xanthine/xanthine oxidase). These results implicate albumin as a major serum survival factor. Inhibition of apoptosis by albumin occurs through at least two distinct mechanisms: carriage of LPA and scavenging of ROS.

Environmental and ethical aspects of international migration.

"U.S. immigration policy has a beneficent intent. However, recent work suggests that the signal it sends internationally--that emigration can be relied upon to relieve local (Third World) population pressure--tends to maintain high fertility rates in the sending country. This effect is counterproductive because high fertility is the primary driver of rapid population growth. In addition, it appears that the relatively open U.S. immigration policy has resulted in a rate of domestic population growth that threatens both the well-being of American labor and cherished environmental values."

Population and women's health.

PIP: Explanations of cultural patterns can be found in the economic context (carrying capacity) in which they develop. Population pressure explains the abuse of women throughout history and in modern times because overpopulation leads to devaluation of women's reproductive capacity. A cultural response to overpopulation includes practices that limit the numbers of women of reproductive age. Such practices foster son preference, which results in selective abortion, female infanticide, neglect and overwork of girls, dowry deaths, and discrimination against widows. The results of these practices are manifest in sex ratios that are culturally rather than naturally controlled and in demographic facts such as the calculation that 60 million females are missing in Asia alone (and perhaps more than 100 million worldwide). Women are also removed from a reproductive setting by being kidnapped or sold into prostitution or by being forced to adopt prostitution for economic survival. In cases where survival is threatened by environmental degradation and population growth, the most harsh cultural practices will emerge to adapt the population to the resources at hand. This situation creates an ethical dilemma posed by the problem of imposing Western values on a culture that is undertaking adaptive practices to insure its very survival. Ways to help women in these situation include limiting population growth humanely through family planning, provision of paid work to women, and creation of an environment that supports a small family ideal. Prosperity itself, through modernization, sometimes causes family sizes to increase. The most important intervention appears to be the provision of paid employment outside the home for women. On the other hand, large-scale wealth transfers and liberal immigration policies simply send signals that population pressure is a regional problem that can be alleviated by the international community. Increasing immigration to developed countries will place pressure on the women of those countries by increasing population. The fact that population size in the US is expected to double in 64 years already poses a threat to the status of US women who are not immune from cultural processes.^ieng

The demographic transition revisited: lessons for foreign aid and U.S. immigration policy.

"The completed demographic transitions in industrialized countries inspired a model which underlies many well-meant policies affecting the Third World. However, the model's postulate--modernization and prosperity will lower fertility rates--has exacerbated rather than helped control worldwide population growth and the associated environmental degradation. Here we show that perceived economic opportunity leads to raising family size targets and to discarding elements of traditional cultures which formerly held fertility rates in check. Conversely, fertility rates fall when limits are recognized. These observations imply that a liberal immigration policy and large-scale foreign aid are counterproductive for restoring balance between population size and carrying capacity."

First do no harm.

Many traditional societies, which have long survived in balance with the carrying capacity of their local environments, have recently experienced rapid rates of population growth that threaten their survival. In examining the reasons for these deleterious trends, the author notes that they have occurred despite international technological assistance, improved health care, increased literacy, democratization, and liberal immigration and refugee policies favoring developing countries. "She argues that well meant programs and policies work at cross purposes with their stated goals when they dispel motivation to exercise caution and restraint. Family size targets stay high or rise when people think that limits which formerly operated have been relieved; so a windfall of resources or emigration opportunity frequently results in a population explosion in the region supposedly being helped."

Parent characteristics and sex differential infant mortality: the case in Tennessee.

Females survive males at most ages in virtually all modern industrialized societies. However, stratification of a sample by socioeconomic indicators shows that white infant male and female postneonatal mortality rates converge as the mothers' or parents' education rises and as the mothers age. These results are congruent with the parental selection hypothesis and with other findings that suggest that families at the pinnacle of the local social structure invest heavily in males and that parents nearing the end of their reproductive career try hard to effect the survival of all offspring.

Antibodies to neutrophil cytoplasmic antigens in Wegener's granulomatosis and other conditions.

The use of serum antibodies to neutrophil cytoplasmic antigens (ANCA) as a diagnostic marker for Wegener's granulomatosis and other forms of vasculitis has been assessed. Although ANCA have been described by several groups the precise antigenic targets are unknown, and detection of ANCA still relies on an indirect immunofluorescence assay technique. Several different patterns of fluorescence have been produced by using sera from different groups of patients, and insufficient information is available on the frequency of positive results and of the patterns of immunofluorescence obtained when serum from patients with vasculitis as a part of a generalised connective tissue disease is used. A study was carried out on serum from 240 patients, including 23 patients with Wegener's granulomatosis, 12 with microscopic polyarteritis, and 30 with various connective tissue diseases. Three patterns of fluorescence were observed: bright coarsely granular cytoplasmic, bright non-granular cytoplasmic, and weak diffuse cytoplasmic. The bright, coarsely granular pattern was 86% specific for Wegener's granulomatosis in this series and was observed in 18 of 23 cases. Other patterns of fluorescence were found in various conditions and were not of diagnostic value. The technique is simple, inexpensive, rapid, and reproducible.

Trends in analgesic self-poisoning in West-Fife, 1971-1985.

All admissions for analgesic self-poisoning to a district poisons unit over a 15-year period have been reviewed. During this time overdose with analgesic drugs increased to represent almost half of all admissions for self-poisoning. The types of analgesics taken in overdose also changed significantly during the period of this review. Aspirin and Distalgesic poisoning declined in incidence and more cases of self-poisoning by paracetamol and non-steroidal anti-inflammatory agents were seen. The impact of these changes on the medical management and outcome of deliberate self-poisoning is analysed. The reasons behind the trends described in this paper are assessed and their implications for future prevention and treatment are discussed.

When a mentally ill woman refuses abortion.

KIE: A case study is presented in which an institutionalized, schizophrenic woman refuses the abortion her legal guardian wants her to have. Her psychiatrist considers her to be incapable of responsible parenthood, and her child would probably be placed in permanent foster care. Mahowald considers a legal determination of the woman's competence to be crucial, although she argues that even a legally incompetent person may be capable of moral decisions. She maintains that, in this case, the moral standing of the fetus supports allowing the abortion refusal to stand. Abernethy assumes that a court would uphold the woman's refusal, but that the decision would be based on a fallacious acceptance of the right to procreate without acknowledging the corresponding responsibility to raise the child.^ieng