The fragile X syndrome.

An amplification of a highly unstable DNA element has been identified at the fragile X locus in Xq27.3. This sequence appears to be both the source of the primary mutation causing the fragile X syndrome, apparently having its causative effect through the methylation of the FMR-1 HTF island and the region of cytogenetic fragility. The direct analysis of the genotype of carrier and affected individuals can be used as a direct diagnosis tool which will improve both the accuracy and speed of diagnosis. The identification of hereditary unstable DNA in a disease with such a wide level of non-penetrance and variable phenotype may give clues as to the basis of non-penetrance in other human genetic disorders.     

Arterial lipid biochemistry in the spontaneously hyperlipidemic Zucker rat and its similarity to early atherogenesis

In the present studies, arterial lipid metabolism was evaluated in the spontaneously hyperlipidemic obese Zucker rat (fa/fa), the lean Zucker rat (Fa/-), and the Sprague-Dawley (SD) rat. Mean serum cholesterol levels in the obese Zucker, lean Zucker and SD rats were 216 +/- 18 mg/dl, 145 +/- 14 mg/dl and 84 +/- 5 mg/dl, respectively. Arterial cholesterol content was in the same rank order as plasma cholesterol and ranged from a mean of 2.23 +/- 0.10 mg/gm wet wt. in the obese rats to 1.36 +/- 0.04 mg/gm wet wt. in the SD rats. The increased arterial sterol in the obese rats was associated with increased lipid metabolism activity. The in vitro incorporation of [14C]oleate into arterial cholesteryl esters was increased 3-4-fold (P less than 0.01) and incorporation into phospholipids and triglycerides was also elevated (P less than 0.001 and P less than 0.01, respectively). The arterial sterol content and arterial lipid metabolism pattern observed in obese Zucker rat aortas are similar to those found in vessels of other species undergoing atherogenic change.     

Monitoring and cerebral protection during carotid endarterectomy.

Two recently published multicentre trials have confirmed the overall benefit of carotid endarterectomy in symptomatic patients with severe carotid artery disease. The key to improving further the long-term advantages of carotid endarterectomy, however, remains the continued reduction of the initial operative risk. While the principal responsibility for this continues to be borne by the surgeon, specifically in reducing technical error, the time is perhaps approaching when he or she might also be able to apply some of the recent advances in cerebrovascular research to reduce operative morbidity still further in the future. This article summarizes the aetiology and pathophysiology of operation-related neurological deficits and reviews current approaches towards intraoperative monitoring, cerebral protection and assessment of quality control.     

Familial Conn's syndrome.

We describe the occurrence of primary hyperaldosteronism in two sisters. Although this is only the second published report of familial Conn''s syndrome, it does have implications for the relatives of patients with Conn''s syndrome and these are discussed.     

Breaking down barriers to treat a patient with a germinoma: a case study.

Germinomas are the most common type of germ cell tumor occurring commonly before the second decade of life. Because of the radiosensitivity of germinomas, traditional treatment following diagnosis has been conventional radiotherapy. The desire to defer radiotherapy to avoid the delayed neurocognitive effects has led researchers to investigate the use of up front chemotherapy. A major limitation in using chemotherapy for brain tumors has been the inability to deliver drugs across the blood brain barrier. The blood brain barrier consortium has developed chemotherapy protocols for patients with malignant brain tumors through the use of reversible osmotic opening of the blood brain barrier. While the patient is under general anesthesia, osmotic opening or disruption is achieved by a 30-second intracarotid infusion of mannitol. The mannitol infusion is followed by both intraarterial and intravenous chemotherapy. By administering chemotherapy in conjunction with blood brain barrier disruption, drug delivery to the tumor and the brain around tumor is increased.     

Translocation t(6;14) as the Sole Chromosomal Abnormality in Adenoid Cystic Carcinoma of the Base of Tongue

We present an adenoid cystic carcinoma of the base of tongue in a 48-year-old male with a restricted chromosomal alteration by cytogenetic and spectral karyotypic analysis (SKY). SKY and G-banding analyses identified the t(6;14)(q25;q13) as the sole structural aberration in all metaphases analyzed. This finding supports a critical role for this event in the development of this tumor. The implications of chromosome 6q translocation in this case and in previously reported adenoid cystic carcinomas are highlighted and discussed.