Lung tumour growth delay and normal tissue toxicity induced by three cytotoxic platinum drugs.

Single doses of the drug cisplatin and its analogues carboplatin and iproplatin were administered to tumour-bearing rats. The tumours used were two bronchial squamous cell carcinomas, that are part of a panel of experimental lung tumours developed at this institute. Cisplatin resulted in severe nephrotoxicity. Carboplatin and iproplatin were less nephrotoxic, but resulted in acute gastrointestinal and (probably) hematological toxicity. Carboplatin also caused late occurring liver damage. The responses of the tumours were compared at the level of maximum tolerated drug doses for early toxicity. The level of response was different for the two tumours. One was more sensitive to the drugs than the other. The effects of cisplatin and carboplatin were approximately similar. Iproplatin was less effective. Because cisplatin caused more severe late toxicity, it is concluded that carboplatin has the best therapeutic index for these two lung tumours.     

Ataxia-Telangiectasia and Xeroderma Pigmentosum: No Evidence of Linkage to HLA

Nine HLA-typed multiplex nuclear families segregating ataxia-telangiectasia (A-T), an autosomal recessive disorder, were studied. Linkage analysis performed by lod scores and by a previously published sib pair method revealed no evidence for linkage between A-T and HLA. An alternative method of linkage detection, previously applied to xeroderma pigmentosum (XP) and HLA, was reexamined and found to contain an error. As a consequence, neither of these "DNA repair disorders" appears to be linked to HLA.     

Clinical and immunological studies in a case of selective complete C1q deficiency

A 10-year-old male with recurrent skin lesions and chronic infections was found to have a selective deficiency of C1q after functional analysis of all complement components. The addition of highly purified human C1q to the patient's serum restored C1 activity, indicating the presence of C1r and C1s and the absence of C1q. Titration of highly purified C1q with patient serum as a source of C1r and C1s resulted in a linear dose-response curve. The undetectable CH50 activity temporarily returned to normal within a few hours of plasma infusion, but the C1 titres were still only 1–3% of normal. Following plasma administration, the peak of C1q activity was reached after 30 min and returned to undetectable levels within 24 hr. The patient serum was not anti-complementary when incubated with normal serum. Nine members of the family, including the parents and two healthy siblings, were subjected to complement studies and HLA typing. The C1 titres and CH50 activity were found to be normal in all except the paternal grandmother who showed reduced levels of all the complement components. There was no linkage for the gene of C1q deficiency and HLA antigens. Among the various laboratory studies performed, anti-smooth muscle antibodies, immune complexes and anti-HBsAg antibody were found to be positive. The child died of a disease compatible with septicaemia. Post mortem tissue studies by light, fluorescent and electron microscopy have shown the presence of a mesangioproliferative glomerulonephritis.     

Effects of the Family Check-Up 4 Health on Parenting and Child Behavioral Health: A Randomized Clinical Trial in Primary Care

The Family Check-Up 4 Health (FCU4Health) is an adaptation of the Family Check-Up (FCU) for delivery in primary care settings. While maintaining the original FCU’s focus on parenting and child behavioral health, we added content targeting health behaviors. This study evaluated whether the adapted FCU maintained positive effects on parenting (positive behavior support, limit setting, parental warmth) and child behavioral health (self-regulation, conduct problems, emotional problems). Pediatric (6–12 years) primary care patients with a BMI?≥?85^th%ile (n?=?240) were recruited from primary care clinics in Phoenix. Children were 75% Latino, 49% female, and 73% Medicaid recipients. This type 2 effectiveness-implementation hybrid trial compared families randomized to FCU4Health (n?=?141) or usual care (n?=?99). FCU4Health was delivered over a period of 6 months. This study focuses on a priori secondary outcomes included parenting and child behavioral health targets of the original FCU, assessed at baseline and 3, 6, and 12 months. Significant improvements were found for the FCU4Health condition, compared to usual care, in parenting from baseline to the 3-month assessment [β?=?.17 (.01; .32)]. Parenting predicted improvements in child self-regulation at 6-months [β?=?.17 (.03; .30)], which in turn predicted reductions in conduct problems [β?=?? .38 (? .51; ? .23)] and emotional problems [β?=?? .24 (? .38; ? .09)] at 12 months. Ethnicity and language of delivery (English or Spanish) did not moderate these effects. The FCU4Health can improve parenting and child behavioral health outcomes when delivered in primary care.

Trial Registration Trial registration number: NCT03013309 ClinicalTrials.gov

     

Long-term health-related quality of life after pancreatic resection for malignancy in patients with and without severe postoperative complications

Background

Surgery for pancreatic cancer yields significant morbidity and mortality risks and survival is limited. Therefore, the influence of complications on quality of life (QoL) after pancreatic surgery is important. This study compares QoL in patients with and without severe complications after surgery for pancreatic (pre-)malignancy.

Differential Expression and Copy Number Variation of Gasdermin (GSDM) Family Members,Pore-Forming Proteins in Pyroptosis,in Normal and Malignant Serous Ovarian Tissue

Inflammation - Gasdermins (GSDM) are members of a family of pore-forming effector proteins which lead to membrane permeabilization and pyroptosis, a lytic cell death with pro-inflammatory...