Phase II trial of piroxantrone in patients with recurrent and metastatic squamous cell carcinoma of the head and neck

Summary Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m² intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic.     

Postprandial induction of chaperone gene expression is rapid in mice.

Molecular chaperones assist in the biosynthesis and processing of proteins. Most chaperones are induced by physiological stresses. We have shown that dietary energy restriction decreases the mRNA and protein levels of many endoplasmic reticulum chaperones in the livers of mice. Here, we have investigated the response of chaperone mRNA to feeding. Control and 50% energy-restricted C3B10RF1 mice were deprived of food for 24 h, fed, and killed 0, 1.5, 5 or 12 h after feeding. Chaperone mRNAs were strongly induced as early as 1.5 h after feeding in control and energy-restricted mice. The integrated levels of these mRNA over 24 h were significantly lower in energy-restricted mice. The mRNA response to energy intake was mirrored over the course of days in the level of chaperone protein. A similar but smaller response to feeding was found in kidney and muscle. Puromycin and cycloheximide failed to inhibit the feeding response, suggesting that feeding releases chaperone expression from an unstable inhibitor. Studies with dibutyryl-cAMP- and glucagon-supplemented, normal and streptozotocin-diabetic mice suggest that glucagon and insulin may be mediators of the feeding response. Adrenalectomy enhanced the feeding induction, but dexamethasone administration had no effect. Thus, postprandial changes in insulin and glucagon may link chaperone gene expression to feeding, possibly in several tissues including liver.     

Family history evaluation as a predictive screen for childhood hypercholesterolemia. Pediatric Practice Research Group

A study was conducted to evaluate the efficacy of family history factors as screening criteria for childhood hypercholesterolemia. When they were seen for routine care at one of eight office practices, 1005 prepubertal children underwent random serum cholesterol determinations. Parental and grandparental histories of cardiovascular risk factors and atherosclerotic complications prior to 55 years of age were also obtained. Of the initial group, 274 children had total cholesterol levels greater than or equal to 175 mg/dL, and 175 of these children returned for retesting after an overnight fast. A total of 88 children were found to have low-density lipoprotein-cholesterol (LDL-C) values greater than or equal to 90th percentile for age and sex. Maternal and paternal histories of hypercholesterolemia were significantly associated with elevated LDL-C (odds ratio = 7.3 and 2.9, respectively), but had extremely low sensitivities (0.09, 0.15) despite modest positive predictive values (0.42, 0.22). Grandparental histories of sudden death, peripheral vascular disease, and gout were associated with elevated LDL-C, but sensitivities and positive predictive values for all of these factors were less than 0.22. Family history factors most commonly recommended as criteria for cholesterol screening in children did not identify half of all the children with elevated LDL-C and did not selectively identify the most severely affected children. Adding information concerning the presence of childhood obesity did not result in appreciable improvement in LDL-C detection beyond that achieved by family history factors alone. It was concluded that if thorough identification of young children with elevated LDL-C is desired, inclusive population screening rather than a family history-based strategy would be the most effective approach.     

Epidural anaesthesia for Caesarean section in patients with active recurrent genital herpes simplex infections: a retrospective review

The safety of epidural anaesthesia in patients with active, recurrent genital herpes simplex (HSV) infections is controversial. We reviewed the six-year experience of the use of epidural anaesthesia in this patient population in two institutions. Eighty-nine parturients with active genital HSV were administered epidural anaesthesia for Caesarean section. No patient suffered an adverse outcome related to either the anaesthetic or the virus. The theoretical risks of regional anaesthesia in the parturient with active herpes genitalis are reviewed. We conclude from available data that the risk of an adverse outcome is small and does not contraindicate the use of epidural anaesthesia in patients with recurrent infection.     

An experimental collagen-impregnated dacron graft: Potential for endothelial seeding

This study evaluates the potential for endothelial seeding of a collagen-impregnated Dacron graft with or without surface modifiers (fibronectin, heparin) to attach and retain these cells during flow. Human umbilical endothelial cells were harvested, cultured, labeled with Indium111-oxine and seeded onto 30 mm X 4 mm diameter grafts. Six graft surfaces were studied: 1) a collagen-impregnated Dacron graft, HemashieldR (C); 2) C + fibronectin (C + F); 3) C + heparin (C + H); 4) C + F + H; 5) HytrelR + F (Hyt + F); and 6) Hyt + F + H. Radioactive loss determined the percentage attachment and then percentage retention of labeled inoculum after a one-hour in vitro perfusion. Scanning electron and light microscopy demonstrated the endothelium on the graft surface following perfusion. Fibronectin-coated grafts had a significantly higher percentage attachment than those without fibronectin (ANOVA, P less than 0.05). However, the percentage retention following perfusion was similar for all Dacron grafts and statistically inferior to the HytrelR grafts studied (ANOVA, P less than 0.05). SEM evaluation of the C + F + H graft surface was qualitatively the most impressive Dacron surface for seeding, yet was inferior to the HytrelR graft. We conclude that fibronectin benefits the initial attachment of endothelium to collagen-coated Dacron rivaling the HytrelR surface. Fibronectin does not improve percentage retention of the HemashieldR surface during perfusion, therefore, some of its initial benefit is lost.     

Natural history of penetrating ocular injury with retinal laceration in the monkey

In one eye each of four cynomolgus monkeys, an 8-mm penetrating injury was made through the equator; there was retinal perforation with vitreous loss. None of the four eyes with this injury developed posterior vitreous detachment or retinal detachment during a follow-up period of 8 months to 1 year.Another group of 26 monkeys had the same injury but also had 0.5 ml autologous whole blood injected into the vitreous at the time of injury. The eyes were examined weekly and enucleated at scheduled intervals from 1 day to 52 weeks post-injury. Posterior vitreous detachment occurred at the earliest at 2 weeks post-injury, and was ultimately present in 91% of the eyes. Vitreous detachment can occur either as a separation at the level of the internal limiting membrane or as a cleavage within the cortical vitreous. Retinal detachment occurred at the earliest at 8 weeks post-injury, and eventually was present in 50% of the eyes. The retinal detachment was tractional; no retinal breaks were detected in any of the eyes.This study was supported by grants EY02061 and EY03040 from the National Institutes of HealthPresented at the 1984 meeting of the Club Jules Gonin in Lausanne, Switzerland