It recently was proposed [Loo, D. D. F., Zeuthen, T., Chandy, G. & Wright, E. M. (1996) Proc. Natl. Acad. Sci. USA 93, 13367-13370] that SGLT1, the high affinity intestinal and renal sodium͞glucose cotransporter carries water molecules along with the cosubstrates with a strict stoichiometry of two Na ؉ , one glucose, and Ϸ220 water molecules per transport cycle. Using electrophysiology together with sensitive volumetric measurements, we investigated the nature of the driving force behind the cotransporter-mediated water flux. The osmotic water permeability of oocytes expressing human SGLT1 (L p ؎ SE) averaged 3.8 ؎ 0.3 ؋ 10 ؊4 cm⅐s ؊1 (n ‫؍‬ 15) and addition of 100 M phlorizin (a specific SGLT1 inhibitor) reduced the permeability to 2.2 ؎ 0.2 ؋ 10 ؊4 cm⅐s ؊1 (n ‫؍‬ 15), confirming the presence of a significant water permeability closely associated with the cotransporter. Addition of 5 mM ␣-methylglucose (␣MG) induced an average inward current of 800 ؎ 10 nA at ؊50 mV and a water influx reaching 120 ؎ 20 pL cm ؊2 ⅐s ؊1 within 5-8 min. After rapidly inhibiting the Na ؉ ͞glucose cotransport with phlorizin, the water flux remained significantly elevated, clearly indicating the presence of a local osmotic gradient (⌬) estimated at 16 ؎ 2 mOsm. In short-term experiments, a rapid depolarization from ؊100 to 0 mV in the presence of ␣MG decreased the cotransport current by 94% but failed to produce a comparable reduction in the swelling rate. A mathematical model depicting the intracellular accumulation of transported osmolytes can accurately account for these observations. It is concluded that, in SGLT1-expressing oocytes, ␣MG-dependent water influx is induced by a local osmotic gradient by using both endogenous and SGLT1-dependent water permeability.

From a population-based sample of 15,504 patients attending Canadian multiple sclerosis (MS) clinics, we have determined the frequency of conjugal MS and have estimated the recurrence risk in offspring of such matings. Twenty-three MS cases were found among 13,550 spouses of study probands for a crude conjugal rate of 0.17% (95% CI of 0.10%-0.24%). Despite ascertainment bias that expectedly inflates this number, this is a frequency intermediate between the point prevalence (0.1%) and lifetime risk (0.2%) for the general population and close to an order of magnitude less than reported for half siblings reared apart (1.06%) from the same population. Six of the 49 offspring of conjugal pairs also had MS, and age conversion gives a rate similar to the concordance rate for Canadian monozygotic twins. However, this correction may not be appropriate in this special case. Despite an ascertainment bias in favor of recognizing affected spouses and a large population sample, the common environment in adulthood shared by spousal pairs could not be shown to increase the risk of conjugal MS. Although the high recurrence rate in offspring is similarly subject to an upward bias, the low risk for MS spouses and the high risk for offspring support other data indicating that familial risk is genetically determined. Furthermore, these results imply that susceptibility alleles are shared by unrelated individuals with the disease.

In 1994, following a request from the ten Provincial Licensing Authorities, the National Dental Examining Board of Canada (NDEB) implemented significant changes to the certification process for dentists seeking a license to practice in Canada. Prior to 1994, graduates of accredited Canadian dental programs were certified without further examination while graduates of United States and other international programs (non‐Canadian, non‐U.S.) were required to complete successfully a written and three‐phase clinical certification examination. Changes implemented in 1994 required graduates of accredited Canadian programs to take both a Written and Objective Structured Clinical Examination (OSCE) Examination. The analysis of the results of the Written Examination for all candidates over the 1994–1996 period supports the following conclusions. There was no meaningful difference in performance of graduates across the ten Canadian dental programs; there was a small difference between the performance of graduates of Canadian and U.S. programs; and Canadian and U.S. graduates performed significantly better than graduates of other international programs. This level of candidate performance and changes to the respective accreditation processes supported the formal agreement providing reciprocal recognition of dental accreditation in Canada and the United States. As of January 1, 1997, graduates of dental programs in Canada and the United States are required to take the same certification examination while international graduates are required to complete a different certification process. These changes to the certification process were ratified by all ten Provincial Licensing Authorities, therefore maintaining a system of national portability for dental licensure in Canada that does not require preclinical or clinical board examinations for graduates of accredited North American dental programs.

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