Self-sufficiency in a regional hospital system.

This article considers measures that indicate the degree of regionalization within a hospital system. In particular, regional independence is characterized with a "self-sufficiency" index. The basis of these measures is the use of facilities in one region by residents of another region, that is, interregional flows. Examples of the use of the suggested measure in the Nova Scotia hospital system are presented.     

Cerebral embolism, marantic endocarditis, and cancer.

Two subjects with cerebral embolism were found at autopsy to have marantic (nonbacterial thrombotic) endocarditis (NBTE) and an unsuspected carcinoma. A additional 16 subjects with marantic endocarditis and cancer were found on reviewing the autopsy records of 22 subjects with NBTE. Of these 18 subjects with NBTE and cancer, eight developed a stroke during their illness, in five as the initial manifestation of cancer. Although the association of cancer and marantic endocarditis is generally well recognized, cerebral embolism from this source should be more seriously considered as one of the "remote effects" of cancer on the nervous system.     

Acute changes in urine protein excretion may predict chronic ifosfamide nephrotoxicity: a preliminary observation

Purpose: To evaluate proteinuria occurring early after ifosfamide therapy and to assess the use of changes in proteinuria in the prediction of severe chronic nephrotoxicity. Methods: One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to characterize urine protein excretion in 12 children with solid tumours before and after the first course of ifosfamide treatment, and in 24 healthy children. Chronic nephrotoxicity was evaluated at 6 months after ifosfamide treatment and graded as none, mild, moderate or severe. Results: Urine from healthy children and from 10 of 12 patients before ifosfamide therapy showed a protein band with a molecular weight (95.4 kDa) corresponding to that of Tamm-Horsfall protein but no lower molecular weight proteins. After the first course of ifosfamide this 95.4-kDa protein was lost in six of ten patients with a concomitant appearance of a low molecular weight proteinuria (<70 kDa) in eight. Tamm-Horsfall protein was lost in two of five patients who subsequently developed no or mild nephrotoxicity and in four of five patients who subsequently developed moderate or severe nephrotoxicity. Conclusions: Early subclinical changes in urine protein excretion after ifosfamide, manifested by a loss of Tamm-Horsfall protein excretion, may be predictive of subsequent chronic nephrotoxicity. Received: 27 August 1996 / Accepted: 25 July 1997     

An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina

Objective Tomap potential sites of sex steroid action in the human vulva.
Methods Monoclonal antibodies to androgen, oestrogen and progesterone receptors were used to stainfrozen sections of vulval skin, vagina and suprapubic skin. A scoring system was devised to comparereceptor distribution in the epidermis and dermis of skin with vaginal epithelium and stroma.
Results Androgen receptors were seen in epidermal keratinocytes, sebaceous glands, sweat glands, hairfollicles and dermal fibroblasts of skin, and epithelial cells and stromal fibroblasts of the vagina. Androgen receptor scores were significantly higher in the epidermis of labia majora and minora thanin vaginal epithelium. Oestrogen receptors were seen in basal and suprabasal cells of vaginalepithelium and epidermis of labia minora but were restricted to basal keratinocytes in true skin.They were seen in stromal fibroblasts and vaginal smooth muscle, and dermal fibroblasts of theskin. Oestrogen receptors were highest in vaginal epithelium and stroma, and lowest insuprapubic skin. Progesterone receptors were seen in vaginal epithelium, fibroblasts and smoothmuscle but not in the vulva. There was no evidence of significant differences in androgen oroestrogen receptor staining in the vulva of pre- or postmenopausal women.
Conclusion The transition from vagina to vulva is marked by an increase in androgen and a decrease inoestrogen and progesterone receptors. This distribution of receptors would indicate a limited role foroestrogen creams on the vulva.     

Norman Bethune and Edward Archibald: sung and unsung heroes

Edward Archibald was a pioneer, master thoracic surgeon. He laid the foundation for surgical research in Canada and made fundamental contributions to the training and certification of surgeons. He did it all without raising his voice and within the confines of organized medicine. He became an unsung hero. Norman Bethune, with a flair for publicity, used extraordinary measures and delivered them heroically with talent and total dedication, ignoring conventional approaches. He became a truly sung hero.     

Oral iron absorption in infantile protein-energy malnutrition.

The ability of infants with protein-energy malnutrition to absorb iron was assessed using the serum iron response to a dose of ferrous sulfate providing 3 mg elemental iron per kg body weight. Responses were grouped as flat (delta serum Fe less than 30 microgram/dl), intermediate (30 to 100 microgram/dl), and normal (greater the 100 microgram/dl). Of 25 consecutively admitted children studied, seven had a flat, five an intermediate, and 13 a normal curve (mean delta serum Fe: 10 microgram/dl, 66 microgram/dl, and 175 microgram/dl, respectively). There were no differences among the three groups in hematocrit, fasting serum iron or transferrin saturation, severity of malnutrition, or evidence of other malabsorption sufficient to explain these differences. Although hematocrits, fasting serum iron, and transferrin saturations did not change appreciably during nutritional rehabilitation, all children with initially abnormal responses subsequently had normal tests.     

Phase I and pharmacologic study of the human DNA methyltransferase antisense oligodeoxynucleotide MG98 given as a 21-day continuous infusion every 4 weeks

Purpose: MG98 is a second generation phosphorothioate antisense oligodeoxynucleotide which is a highly specific inhibitor of translation of the mRNA for human DNA MeTase I (DNMT 1). This phase I study examined the toxicity and pharmacologic profile of MG98 administered as a continuous 21-day intravenous infusion every 4 weeks. Patients and methods: Fourteen patients with solid cancers received a total of 25 cycles of MG98 at doses ranging from 40 to 240 mg/m²/day. Steady-state concentrations of MG98 were measured as were several pharmacodynamic assessments including mRNA of the target gene, DNMT1, in PBMC. In addition, other potential surrogate markers of drug effects were explored, including hemoglobin F, Vimentin and GADD45. Results: Dose limiting effects were drug-related reversible transaminase elevation and fatigue seen at doses of 240, 200 and 160 mg/m²/day. The dose level of 80 mg/m²/day was felt to be safe and tolerable when delivered on this schedule. No evidence of antitumor activity was observed. Although pharmacokinetic analysis revealed that at the higher dose levels, mean Css values of MG98 were approximately 10-fold times the IC₅₀ values associated with target inhibition in vitro, the extent of MG98 penetration into target tumors in this trial was not determined. No consistent, dose-related changes in correlative markers including DNMT1 mRNA, hemoglobin F, Vimentin and GADD45, were observed. Conclusions: This schedule of MG98 given as a 21-day continuous intravenous infusion every 4 weeks was poorly tolerated in the highest doses; therefore, further disease-site specific evaluation of the efficacy of this agent will utilize a more favorable, intermittent dosing schedule. Pharmacodynamic evaluations undertaken in an attempt to explore and validate the biological mechanisms of MG98 did not show dose-related effects.     

Characterization of an in vitro intervertebral disc organ culture system

Intervertebral disc organ culture has the capacity to control mechanical and chemical boundary conditions while keeping the tissue largely intact, and allowing interventions that would be impossible or unethical on animal studies. Recent studies on ex vivo organ culture has mostly involved small animals, or been limited to development and validation studies. In this study, bovine caudal discs were used. The large animal model design ensures that sufficient tissue is available for measurement of multiple dependent variables on the same disc, and a similar aspect ratio, diffusion distance, composition and rate of proteoglycan synthesis to human lumbar discs. The first goal of this study was to refine a set of dependent variables capable of characterizing the response of the intervertebral disc to culturing and to develop a technique to measure cell viability in all three regions of the disc. The second goal was to use these variables to compare static and diurnal loading as a method of maintaining intervertebral disc structure, composition, and cell metabolism similar to the in vivo state. Static (0.2 MPa) and diurnal loading (0.1 and 0.3 MPa alternating at 12 h intervals) were applied and intervertebral discs were examined after 4 or 8 days with dependent variables including changes in geometry (disc height and diameter), composition (tissue water content, tissue proteoglycan content and proteoglycan content lost to the culture media), cell viability and metabolism (proteoglycan synthesis). Results indicate that there was a decrease in disc height and water content after culture regardless of culture duration or loading condition. Cell viability significantly decreased with culture duration in the inner annulus and nucleus; however, a significant reduction in cell viability for the diurnal versus static loading condition was only observed after 8 days in the nucleus region. No significant differences were seen in viability of the outer annulus region with time, or in any loading groups. We conclude that our system is capable of keeping bovine caudal discs alive for at least 8 days without significant changes in GAG content, or cell metabolism, and that static loading was slightly better able to maintain cell viability than diurnal loading. This system offers promise for the future studies on large intervertebral discs requiring measurements of multiple mechanical and biological dependent variables on the same tissue.