Kidney Preservation for Transportation: IV. Eight-Thousand-Mile International Air Transport1

Eleven do kidneys were removed in Los Angeles, preserved, and air-freighted in small insulated boxes to London, Tel Aviv and Sydney. They were allografted into bilaterally nephrectomized dogs after storage periods of 14 to 23 hours. Except in the case of one technical failure, the rise in serum creatinine in the recipients was minimal, reaching on the average 2.2 ± SD 0.5 mg/100 ml. This simple method of preservation, involving flushing with a new perfusate and storage in ice, could provide a solution to the problem of transporting cadaver kidneys to histocompatible recipients. Survival of two out of three kidneys stored for 48 hours was also obtained.     

Oropharyngeal cancer pathogenesis: ubiquitin proteolytic, apoptotic and epidermal growth factor related pathways act in concert--first report

The current study was carried out to examine the clinical characteristics and survival-probability rates of 51 patients treated for oral (tongue) cancer and to correlate it with various tumor markers. The clinical data and survival probability rates were correlated with the immunohistological analysis of p27, Skp2, p53, Bcl-2, TUNEL (apoptotic rate) and c-erbB-2 markers. The 5-year survival-probability correlated with staging, grading and base of tongue location. An inverse relation between the expression of p27 and Skp2, p27 and grading, and a direct relation between Skp2 and grading were demonstrated. Concomitantly, significant correlations between low p27, high Skp2 and high TUNEL (apoptotic rate) expressions and between low p27 and high c-erbB-2 (Her2) expressions in the cancer lesions were demonstrated. The accumulated data may be employed in the future for a better understanding of the biology behind oral cancer and for developing better means of detection and treatment.     

Mutational analysis of <Emphasis Type="BoldItalic">hMsh6</Emphasis> in Israeli HNPCC and HNPCC-like Families

Germline mutations in DNA mismatch repair (DNA-MMR) genes, mainly hMlh1 and hMsh2, underlie Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Germline hMSH6 gene mutations have been reported in a small subset of HNPCC families. In the present study, ethnically diverse individuals with HNPCC and HNPCC-like features were genotyped for hMsh6 germline mutations using exon-specific PCR, DGGE, and DNA sequencing. The study encompassed 92 individuals representing 88 unrelated families who were previously analyzed for Msh2 and Mlh1 mutations: Jewish Ashkenazim (n = 44), non-Ashkenazim (n = 27), Israeli Moslem-Arab (n = 15), Druze (n=3), and Cypriot non-Jews (n = 3). Of the study population, 71 had colon cancer (CRC), mean age at diagnosis was 50.9±13.2 years (range16–73 years), 5 had endometrial cancer (two with concurrent CRC), (mean 43.6±3.26 years, range 38–45 years), and unaffected individuals (n = 18) were first degree relatives within HNPCC families and were genotyped at a mean age of 48.3±11.7 years (range 30–69 years). Of the 92 individuals analyzed, none showed a truncating hMsh6 mutation, and 6 (6.6%) harbored one of three germline missense mutations: a previously reported one (V878A), and two novel mutations (V509A, S227I). The pathogenic significance of these three missense mutations is yet unclear. In addition, 5 polymorphisms were detected, 2 of which were novel. We conclude that the rate of pathogenic hMsh6 mutations in HNPCC families of Jewish and Mediterranean origin is low, and that mutations in other genes probably account for the phenotype in these families.     

Dying dementia patients: too much suffering, too little palliation

Patient suffering is a pathological syndrome traditionally viewed as encompassing psychological distress, spiritual concerns, and various aspects of physical pain. There is insufficient clinical evidence for suffering in dying dementia patients, which may lead to inappropriate evaluation and insufficient palliative treatment. Our objective was to evaluate the suffering of terminal dementia patients over time, from admission to a geriatric ward to the last day of life. The study included consecutive end-stage dementia patients in a general geriatric department of a tertiary hospital. Patients were evaluated weekly by the Mini Suffering State Examination scale (MSSE) which measures many domains related to suffering. Seventy-one patients were studied. Mean survival of patients was 38.0 +/- 5.1 days. MSSE increased during hospital stay from 5.62 +/- 2.31 to 6.89 +/- 1.95 (p < 0.001). According to MSSE scale, 63.4 percent and 29.6 percent of patients died with a high and intermediate level of suffering, respectively. Only 7 percent of the patients died with a low level of suffering. In particular, patients were restless (p < 0. 001), had pressure sores (p = 0.01), and were considered medically unstable (p < 0.001). We concluded that, despite traditional medical and nursing care, a large proportion of dying dementia patients experience an increasing amount of suffering as they approach death. New palliative treatment approaches should be developed for these patients.     

Recurrent herpes simplex encephalitis

Recurrent herpes simplex virus (HSV) encephalitis is a rare disorder with only a few cases reported. We report a case of HSV encephalitis with documented recurrence in the same anatomic location, lending support to the theory of reactivation as the mechanism of disease.     

Healing of dehiscence-type defects in implants placed together with different barrier membranes: a comparative clinical study

OBJECTIVE: Premature exposure of membranes used in guided bone regeneration (GBR) results in decreased bone formation. The effect of an expanded polytetrafluoroethylene (e-PTFE) and two collagen membrane on bone healing of buccal dehiscence defects around implants in cases with and without premature membrane exposure was clinically evaluated. METHODS: Three groups were established: Group OS (Ossix, n=73 implants, 41 patients), Group BG (Bio-Gide, n=53 implants, 28 patients) and Group GT (e-PTFE, Gore-Tex, n=34 implants, 17 patients). Defect height and width were measured at the time of implant placement and at second stage surgery. Surface area was calculated as half ellipses. When several implants were placed simultaneously, a mean of their defect width and height was calculated. RESULTS: Mean percentage reduction of defect area (92.2+/-13.78% Group OS, 94.6+/-6.69% Group BG, and 97.3+/-4.91% Group GT) and height (81.6+/-23.19%, 85.4+/-12.26%, and 93.4+/-9.39% respectively) did not show statistically significant differences between groups. Differences between groups were not statistically significant for all parameters when cases without spontaneous membrane exposure were compared. However, differences were significant when spontaneous membrane exposure occurred. Mean percentage reduction of defect area among cases where membrane exposure occurred was 91.5+/-10.86% Group OS, 71.5+/-8.61% Group BG, and 73.7+/-13.97% Group GT. Mean percentage reduction of defect height among cases with membrane exposure was 76.4+/-18.28%, 53.4+/-9.86%, and 49.4+/-11.05%, respectively. CONCLUSIONS: Premature exposure of membranes and subsequent and consequent exposure of implants results in impaired bone healing. Certain barrier membranes, as used in group OS, are apparently capable of supporting gingival healing even when prematurely exposed that could be advantageous in GBR procedures.     

The familial Mediterranean fever (MEVF) gene as a modifier of Crohn's disease

OBJECTIVES: Crohn's disease (CD) has been reported to be more frequent among non-Ashkenazi Jewish patients suffering from familial Mediterranean fever (FMF). Interestingly, functional similarities between the CD susceptibility gene (NOD2/CARD15) and the FMF gene (MEFV) have been described: both belong to the death domain containing protein family, important in the regulation of apoptosis, cytokine processing and inflammation. AIMS: To investigate the prevalence of MEFV mutations in Jewish non-Ashkenazi CD patients and its putative effect on CD presentation. METHODS: Germline DNA of 105 Israeli CD patients of non-Ashkenazi and mixed Ashkenazi-non-Ashkenazi ethnic background was analyzed for three most common MEFV mutations: M694V, V726A, and E148Q. Five patients (4.7%) with a clinical diagnosis of FMF were included. Data obtained from each patient included: age of onset, disease location, and behavior, the presence of extraintestinal manifestations of CD and therapeutic regimens. RESULTS: The overall prevalence of mutation carriers among non-FMF-CD patients was 13% (13/100). A stricturing disease pattern was observed in 56% (10/18) of all carriers, FMF-CD, and non-FMF-CD patients, and in 25% (22/87) of noncarriers (OR: 3.7, 95% CI: 1.3-10.5, p= 0.015). The prevalence of fistulas was comparable in both groups. Extraintestinal manifestations were significantly more frequent among carriers than noncarriers (65%vs 32%, OR 3.9, 95% CI = 1.3-11.5, p= 0.015). No differences were observed in disease location and disease severity. CONCLUSIONS: MEFV mutations are not associated with CD susceptibility, yet the presence of these mutations appears to be associated with a stricturing disease pattern and extraintestinal disease manifestations of CD.     

Limited use of complementary and alternative medicine in Israeli head and neck cancer patients

HYPOTHESIS/OBJECTIVE: The use of complementary or alternative medicine (CAM) is growing among cancer patients. A Medline search failed to reveal any dedicated report of CAM use specifically in patients with head and neck cancer (HNC). STUDY DESIGN: Use of CAM was evaluated in a cohort of treated HNC patients. METHODS: Patients treated for HNC were asked if they had used CAM since their diagnosis. Demographic data and data pertaining to mode of CAM, duration of treatment and effects were obtained. RESULTS: One hundred forty-three patients (mean age 61 years) were included. Only nine patients (6.3%) reported using disease related CAM. This included acupuncture (4), Reiki (2), naturopathy (2), hypnosis (1), shiatsu (1), chiropractic treatment (1), homeopathy (1), and selenium (1). CONCLUSION: Contrary to the reported use, few of our HNC patients used CAM. Although this could be related to good caregiver-patient relationship, further studies in comparable populations are warranted to evaluate if this is a local or a pervading finding in head and neck cancer patients.     

Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?

Present knowledge on the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) deficiency on aging and lifespan are controversial. Studying untreated patients with either isolated GH deficiency due to GH gene deletion, patients with multiple pituitary hormone deficiency due to PROP-1 gene mutation and patients with isolated IGF-I deficiency due to deletions or mutations of the GH receptor gene (Laron syndrome); it was found, that these patients despite signs of early aging (wrinkled skin, obesity, insulin resistance and osteopenia) have a long life span reaching ages of 80-90 years. Animal models of genetic GH deficiencies such as Snell mice (Pit-1 gene mutations) the Ames mice (PROP-1 gene mutation) and the Laron mice (GH receptor gene knock-out) have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting high amounts of GH have premature death. Those data raise the question whether pharmacological GH administration to adults is deleterious, in contrast to policies advocating such therapies.