Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans.

In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.

Mural thrombus endocarditis complicating an acute myocardial infarction. Report of a case.

Myocardial abscesses complicating a myocardial infarction are rare. Before this case, to our knowledge, there have been no previously reported cases in which patients have survived. We report here a surgical cure of a mural thrombus cardiac abscess.

Lack of significant long-term sequelae following traumatic myocardial contusion.

We assessed the possibility of long-term functional cardiac sequelae in patients who had sustained a traumatic myocardial contusion (group 1) by comparing this group with a cohort group of patients with similar traumatic injuries but exclusive of the cardiac component (group 2). More than one year following injury, patients in group 1 were qualitatively indistinguishable from patients in group 2 according to the New York Heart Association classification. Both the left and the right ventricular ejection fractions, less in group 1 than in group 2 immediately following trauma, were similar between groups during follow-up study at rest. During exercise to maximal work load at follow-up, changes in the mean right and left ventricular ejection fractions were also similar between the two patient groups. We therefore concluded that traumatic myocardial contusion to the left and/or right ventricle almost always resolves without significant functional sequelae within one year of injury.

Are all RAS mutations the same? Coexisting KRAS and NRAS mutations in a caecal adenocarcinoma and contiguous tubulovillous adenoma.

Mutations of the human Kirsten rat sarcoma viral oncogene homologue (KRAS) and the highly homologous human neuroblastoma RAS viral oncogene homologue (NRAS) are associated with resistance to antiepidermal growth factor receptor therapies in patients with colorectal cancer. In this report, we describe a caecal adenocarcinoma that contains both KRAS c.35G>T (G12V) and NRAS c.34G>A (G12S) mutations. The adenocarcinoma arises from a contiguous high-grade tubulovillous adenoma, which also carries the identical KRAS and NRAS mutations, supporting their common origin. While KRAS mutations are common in colorectal cancers, NRAS mutations are relatively rare and the coexistence of multiple RAS mutations is not documented, presumably reflecting similar functions of wild-type and mutant forms of RAS. Recent experimental evidence has suggested that KRAS and NRAS may in fact mediate distinct biological processes in the colon, and this unusual case potentially illustrates the hypothesis clinically. Characterisation of the diverse and divergent functions of RAS family members and mutant forms of RAS in the colon form important considerations for the development of RAS-targeting therapeutics.

Organization and operation of a home parenteral nutrition program with emphasis on the pharmacist's role.

A home parenteral nutrition program was organized at Mayo Clinic-Rochester Methodist Hospital in 1975. To date, 26 patients with chronic malnutrition usually due to either severe short bowel syndrome or extensive Crohn's disease have been trained in home parenteral nutrition for a total treatment period of 430 patient-months. Home parenteral nutrition is an attractive alternative for these patients in that it dramatically improves nutrition, promotes rehabilitation at home, and probably decreases long-term expenses. The numerous medical, psychosocial, and financial problems confronting patients on home parenteral nutrition are managed through a multispecialty team consisting of physicians, pharmacists, nurse, social worker, dietitian, physiatrist, psychiatrist, and business manager. The pharmacist is the person with whom the patient has the most contact during a 2-week training period. In addition to patient education, the pharmacist coordinates the transition to home care, offers in-service education on home parenteral nutrition to nurses and house officers, tests and evaluates the equipment, coauthors a training manual, and edits a quarterly newsletter to patients who are on home parenteral nutrition.

A singular dermatosis of Mongols.

A long-term, erythematous, follicular papular dermatosis affecting the presternal and interscapular skin was found to occur in subjects with Down's syndrome. One hundred seventy-four subjects (110 male and 64 female) were surveyed. The condition was seen in 46% of the males, with the highest incidence in patients who were between 20 and 40 years of age; the condition was rare in the females. Our findings suggest that this condition is much commoner than any other abnormal skin feature described in the literature on Down's syndrome.

Health practices and hardiness as mediators in the stress-illness relationship.

Two stress and illness models that include the joint mediating effects of health practices and hardiness were tested prospectively over a 2-month period. At the beginning of one academic quarter, 60 female and 26 male undergraduate students completed five subscales indexing hardiness. Stress, health practices, and illness for the prior month were assessed at this time as well as 1 and 2 months later. Stress was measured by the number of negatively rated stressors reported on the Life Experiences Survey. Health practices were measured by the Self Care Inventory. In the first model, illness was measured by the severity of physical symptoms reported on the Seriousness of Illness Rating Scale; in the second model, it was measured by the number of symptoms reported. Correlations between all measures of stress and illness were typical for life events research (r = .22 to .29). In both models, path analyses revealed that stress acted directly to affect illness as well as indirectly by changing health practices. Hardiness also had a direct effect on illness as well as in indirect effect through health practices. Hardiness did not appear to have a stress-buffering effect on illness; rather, its effects on illness appeared to be independent of its effects on stress. Implications for life events research are discussed.

Effects of taipan (Oxyuranus scutellatus) venom on erythrocyte morphology and blood viscosity in a human victim in vivo and in vitro.

The case of a snake handler with envenoming due to Australian taipan (Oxyuranus scutellatus) showing marked morphological changes in his red blood cells is presented. The red cells underwent sphero-echinocytic transformation and in subsequent experiments in vitro the effects of taipan venom on red cells were further characterized. Taipan venom induced sphero-echinocytic transformation at nanogram/ml concentrations and led to a marked increase in whole blood viscosity. These changes have not been featured in previous reports of taipan envenomation and are reported to highlight the diagnostic value of blood film examination in cases of suspected envenomation. The significance of the hyperviscosity, and consequent reduction in blood fluidity, is unknown and requires further investigation.

How children die in hospital.

A retrospective analysis was performed to describe the course of terminal care provided to dying hospitalized children in terms of symptom assessment and management, and communication and decision-making, at the end of life. Seventy-seven of 236 infants and children who died after hospital admission in Edmonton, Canada between January 1996 and June 1998 met entry criteria. Only children who died after a minimum hospitalization of 24 hours in the case of chronic illness or after a minimum hospitalization of 7 days following an acute event were included. Unanticipated deaths were excluded. Eighty-three percent of children died in intensive care settings (64/77), and 78 % (60/77) were intubated prior to their death. Symptoms were recorded in narrative progress notes. Five of 77 (6%) charts contained specific pain assessment and treatment records. Opioid analgesia was provided in 84 % of all cases (65/77). Six (8 %) patients had do not resuscitate (DNNR) orders preceding final hospital admission and 56/71 (79%) remaining patients had documented discussion resulting in DNR decision during final hospital admission. Median time from DNR to death was < 1 day. Mode of death was withdrawal of therapy in 33/77 (43 %), no cardiopulmonary resuscitation (CPR) in 26/77 (34 %), andfailed CPR in 13/77 (17%). Five children were declared brain dead. In only one case was there evidence in the medical record of the possibility of death being discussed explicitly with the patient. Decision-making regarding end-of-life issues in this pediatric population was deferred very close to the time of death, and only after no remaining curative therapy was available. Acuity of care was very high prior to death. Children are rarely told that they are dying.

Molting of Rotylenchus buxophilus Golden.

Molting of Rotylenchus buxophilus is similar in all observed post-embryonic stages. During molting the old cuticle and cephalic framework, conus of the old stylet, vestibulum extension, linings of amphids, distal part of the linings of the excretory duct, rectum, and phasmids are shed. The new styler is formed starting from the conus, which is simultaneously formed in its entirety.

Reducing bias in estimates of the richards growth function shape parameter.

A process error model developed by White and Brisbin (1980) is used frequently for estimation of the parameters of the Richards sigmoid growth function. The Richards function includes a parameter, m, that describes the shape of familiar three-parameter functions, such as the monomolecular (m = 0), von Bertalanffy (m = 2/3), Gompertz (m----1) and logistic m = 2), as well as other sigmoid functions. We show that this model systematically underestimates the shape parameter, m. In calibration runs and simulations, bias decreased with increased frequency of sampling during the period of rapid growth and with smaller values of true m. Relative bias was insensitive to the magnitude of m. A simple correction reduced the bias to negligible values for both deterministic and stochastic process error models. Biases in estimated asymptote, A, and growing time, T, were small for a variety of sampling intervals and shape parameters.

Evaluation of a farm safety day program: participants and non-participants over a one-year follow-up period.

Farm safety day programs are attended each year by thousands of children in rural communities. This evaluation of a national farm safety day program assessed changes in knowledge and reported behaviors among safety day participants, aged 8 to 13 years, and a comparison group of children who did not attend a safety day. The outcome evaluation involved a quasi-experimental design with participants and non-participants, measured with a pre-test, three-month telephone follow-up, and one-year telephone follow-up survey. The study included 621 children from a sample of 28 safety days administered throughout North America and 413 non-participants recruited from the same or nearby communities. The survey instruments measured participants' knowledge of safety hazards, knowledge of appropriate safety behaviors, and current practices with regard to safety behaviors. While both participants and non-participants showed improved safety knowledge and safe behavior scores over time, there were significantly greater increases in knowledge and behaviors for the safety day participants than for the non-participants. Improvements occurred for all age levels and were sustained through the one-year follow-up assessment. This study contributes to the body of evidence that such safety programs can have a long-term effect on the knowledge and safe practices of children who attend them.

Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats.

Oral naltrexone is used to treat alcohol and heroin dependence but is associated with poor patient compliance. Sustained-release preparations have been developed to overcome noncompliance. Many sustained-release preparations are composed of polymers combined with naltrexone. Limited data indicate that polymers induce variable levels of tissue reactivity and that naltrexone may increase this effect. A slow-release subcutaneous naltrexone-poly (DL-lactide) implant is currently being trialed to treat heroin dependence in Western Australia. A minority of women fall pregnant and, although tissue reactivity in nonpregnant humans is relatively minor, detailed chronological data during pregnancy are lacking. Histological changes in pregnant rats were assessed; a single active tablet containing poly[trans-3,6-dimethyl-1,4-dioxyane-2,5-dione] (DL-lactide) loaded with 25 mg of naltrexone was implanted subcutaneously, and tissue response was compared with inactive polymer implantation. Rats were timed mated at 13-26 days postimplant. Tissue assessment up to 75 days by a pathologist showed that naltrexone induced chronic inflammatory response in a dose-dependent manner, although still at a low level. Furthermore, for inactive implants, minimal foreign body reaction and fibrosis, together with low-level inflammation, suggested good long-term biocompatibility. We conclude that the Australian naltrexone-poly(DL-lactide) implant is tolerated in pregnant rats, reinforcing its potential role for managing alcohol and heroin dependence in pregnant humans.