Low-dose Cyclopenthiazide in the Treatment of Hypertension: A One-year Community-based Study

After an 8-week placebo period, 73 patients whose diastolicblood pressures were between 90 and 110 mmHg were randomly assignedto receive 125 µg (low dose) or 500 µg of cyclopenthiazide(standard dose) for a period of one year. Blood pressure wasmeasured in the patient's home by the same observer at two-weeklyintervals during an 8-week placebo run-in period, every 4 weeksfor a further 12 weeks and at 24, 36 and 52 weeks thereafter.Serum potassium, urate, glucose, glycosylated haemoglobin, totaland HDL cholesterol, and apolipoproteins were measured at theend of the placebo period and at 4, 8, 24 and 52 weeks of activetreatment. Twelve of the 73 patients had an inadequate antihypertensiveresponse—five on the higher dose and seven on the lowerdose. One patient receiving 500 µg was withdrawn becauseof adverse effects. In the remaining 60 patients, systolic anddiastolic blood pressures were significantly reduced when comparedwith pretreatment values in both treatment groups throughoutthe one year period. The decreases in blood pressure were notsignificantly different from each other (p>0.65). Three patientson 500 µg required potassium supplements. Maximum decreasesin the serum potassium of 0.52 mmol/l(500 µg dose) and0.14 mmol/l(125 µg dose) were observed at 24 weeks oftreatment in the remaining 57 patients. The differences betweenthe two doses at this time were statistically significant (p< 0·05), as were the increases in serum urate observedat 4, 8 and 24 weeks (p<0.05). Five hundred micrograms ofcyclopenthiazide increased total serum cholesterol at eightand 24 weeks (0.35, 0.36 mmol/l respectively) when comparedwith pretreatment values (p<0.01) and almost achieved statisticalsignificance when compared with the corresponding low dose value(p = 0.066). This study confirms that 125 µg of cyclopenthiazideis a useful antihypertensive agent with a favourable metabolicprofile which is maintained in the long term.     

Serological confirmation of human T-lymphotropic virus type I infection in healthy blood and plasma donors

We wished to develop criteria for serological confirmation of human T- lymphotropic virus type I (HTLV-I) infection in healthy donors. Selected serum or plasma samples reactive by HTLV-I enzyme immunosorbent assay or gel-agglutination assays with at least one viral- specific band on Western immunoblot (WIB) were tested in six laboratories by four WIBs and four radioimmunoprecipitation assays (RIPAs) for antibodies to HTLV-I proteins encoded by gag (p19 and p24), env (gp46 and/or gp61), and tax (p40x) genes. One hundred forty-two donor sera were obtained from 38 Japanese, 69 American, and 35 Caribbean blood or plasma donors. Among these samples, WIB assays appeared more sensitive to p24 antibodies, whereas RIPAs were significantly more sensitive to gp61 antibodies. All sera (137) with gp61 antibodies had p24 antibodies. Of the 137 sera positive for p24 and gp61 antibodies, p19 antibodies were detected in 129 sera, and p40x antibodies were detected in 108. In sera with p19 antibodies and antibodies to env- or tax-encoded proteins, p24 antibodies were always present. Antibodies to p40x were not found in the absence of gp61 antibodies. Virological evidence of infection was found in seven American donors by lymphocyte coculture (one HTLV-I, one HTLV-II) or by polymerase chain reaction (three HTLV-I, two HTLV-II). Sera from all seven donors showed p24 and gp46 and/or gp61 antibodies. We suggest that seroreactivity to both p24 and gp46 and/or gp61 by WIB or RIPA or both are suitable criteria to confirm but not to distinguish HTLV-I and HTLV-II infections.     

Timing of insulin basal rate reduction to reduce hypoglycemia during late post-prandial exercise in adults with type 1 diabetes using insulin pump therapy: A randomized crossover trial

AimsTo compare the efficacy of three timings to decrease basal insulin infusion rate to reduce exercise-induced hypoglycaemia in patients with type 1 diabetes (T1D) using pump therapy.MethodsA single-blinded, randomized, 3-way crossover study in 22 adults that had T1D > 1 year and using insulin pump > 3 months (age, 40 ± 15 years; HbA_1c, 56.3 ± 10.2 mmol/mol). Participants practiced three 45-min exercise sessions (ergocyle) at 60% VO_2peak 3 hours after lunch comparing an 80% reduction of basal insulin applied 40 minutes before (T-40), 20 minutes before (T-20) or at exercise onset (T0).ResultsNo significant difference was observed for percentage of time spent < 4.0 mmol/L (T-40: 16 ± 25%; T-20: 26 ± 27%; T0: 24 ± 29%) (main outcome) and time spent in target range 4.0–10.0 mmol/L (T-40: 63 ± 37%; T-20: 66 ± 25%; T0: 65 ± 31%). With T-40 strategy, although not significant, starting blood glucose (BG) was higher (T-40: 8.6 ± 3.6 mmol/L; T-20: 7.4 ± 2.5 mmol/L ; T0: 7.4 ± 2.7 mmol/L), fewer patients needed extra carbohydrates consumption prior to exercise for BG < 5.0 mmol/L (T-40: n = 3; T-20: n = 5; T0: n = 6) as well as during exercise for BG < 3.3 mmol/L [T-40: n = 6 (27%); T-20: n = 12 (55%); T0: n = 11 (50%)] while time to first hypoglycaemic episode was delayed (T-40: 28 ± 14 min; T-20: 24 ± 10 min; T0: 22 ± 11 min).ConclusionDecreasing basal insulin infusion rate by 80% up to 40 minutes before exercise onset is insufficient to reduce exercise-induced hypoglycaemia.     

The relationship between surname frequency and Y chromosome variation in Spain

In most societies, surnames are passed down from fathers to sons, just like the Y chromosome. It follows that, theoretically, men sharing the same surnames would also be expected to share related Y chromosomes. Previous investigations have explored such relationships, but so far, the only detailed studies that have been conducted are on samples from the British Isles. In order to provide additional insights into the correlation between surnames and Y chromosomes, we focused on the Spanish population by analysing Y chromosomes from 2121 male volunteers representing 37 surnames. The results suggest that the degree of coancestry within Spanish surnames is highly dependent on surname frequency, in overall agreement with British but not Irish surname studies. Furthermore, a reanalysis of comparative data for all three populations showed that Irish surnames have much greater and older surname descent clusters than Spanish and British ones, suggesting that Irish surnames may have considerably earlier origins than Spanish or British ones. Overall, despite closer geographical ties between Ireland and Britain, our analysis points to substantial similarities in surname origin and development between Britain and Spain, while possibly hinting at unique demographic or social events shaping Irish surname foundation and development.     

Point mutations in the conserved box 1 region inactivate the human granulocyte colony-stimulating factor receptor for growth signal transduction and tyrosine phosphorylation of p75c-rel

The human granulocyte colony-stimulating factor receptor (hG-CSFR) belongs to the cytokine receptor superfamily. As with other members of this family, the cytoplasmic domain of hG-CSFR lacks intrinsic tyrosine kinase activity. To identify critical regions mediating growth signal transduction by hG-CSFR, deletions or site-directed amino acid substitutions were introduced into the cytoplasmic domain of hG-CSFR, and the mutant cDNAs were transfected into the murine interleukin-3 (IL- 3)-dependent Ba/F3 and FDCP cell lines. Truncation of the carboxy- terminal end of the receptor to the membrane-proximal 53 amino acids of the cytoplasmic domain, which retained the conserved Box 1 and Box 2 sequence motifs, decreased the ability of hG-CSFR to transduce G-CSF- mediated growth signals without an associated loss in receptor binding affinity. Substitution of proline by alanine at amino acid positions 639 and 641 within Box 1 completely abolished the G-CSF-mediated growth signal. Rapid induction of tyrosine phosphorylation of several cellular proteins, including a 75-kD protein (p75) identified as c-rel, was an early event associated with transduction of proliferative signals by hG- CSFR in Ba/F3 transfectants. Mutant receptors containing Pro-to-Ala substitutions that inactivated the receptor for mitogenic activity also inactivated the receptor for tyrosine-specific phosphorylation of p75. These results show that the conserved Box 1 sequence motif (amino acids 634 to 641) is critical for mitogenesis and activation of cellular tyrosine kinases by hG-CSFR.     

Taste dysfunction: a practical guide for oral medicine

Oral Diseases (2010) 17 , 2–6 Dental practitioners are often the first clinicians to be presented with complaints about changes in taste. This raises a problem in terms of appropriate evaluative response. It is a difficult issue both because of the common confusion between smell and taste problems (with smell being the more vulnerable sense and contributing substantially to the flavor of food that most patients equate with ‘taste’), and because of the lack of widely accepted standardized techniques to assess true taste function. This brief review provides a summary of some of the problems associated with assessing taste function in a clinical setting and of patient management options available to the practitioner of oral medicine.     

THE ANTIPHOSPHOLIPID OR HUGHES' SYNDROME: AN UNDERDIAGNOSED CAUSE OF THROMBOSIS

The antiphospholipid or Hughes' syndrome is the association between antiphospholipid antibodies, recurrent venous and arterial thromboses and recurrent fetal loss. There are many clinical manifestations arising from this acquired thrombophilia and these are described in the article. The pathogenic mechanism by which the antibodies cause thrombosis is the subject of much debate, and current theories are described. The diagnosis and management of patients with the syndrome are also discussed.