Heart valve surgery in patients with homozygous sickle cell disease: A management strategy

Background:

Patients with the homozygous sickle cell disease have increased perioperative mortality. Some indications like heart valve surgery, may justify an exchange blood transfusion to reduce the proportion of hemoglobin S (HbS) and complications.

Subjects and Methods:

We report two female cases aged 20 and 27, of African origin with homozygous sickle cell anemia who underwent heart valve surgery to treat mitral valve regurgitation. This presentation describes the perioperative considerations including anesthesia and postoperative care.

Results:

A partial exchange blood transfusion decreased HbS levels from respectively, 90% and 84%, 9% to 27% and 34%, and simultaneously treated the anemia. Neither sickling crisis nor acidosis occurred in any patient, and no special postoperative complication occurred. Average hospital stay was 10 days. Currently, the two patients remain alive and free of cardiac symptoms.

Discussion:

Although the presence of sickle cell disorders is associated with increased risk of sickling and thus vaso-occlusive complications, they should not be taken as a contraindication for heart valve surgery. Nevertheless, monitoring of certain parameters such as venous, arterial oxygen content, pH, and body temperature is mandatory for a better outcome. Furthermore, preoperative exchange transfusion has a positive influence on the outcome of surgery and on the survival of patients undergoing heart valves surgery. Avoiding intraoperative hypoxia, hypothermia, and vaso-constrictive agents, minimizing HbS levels with preoperative exchange transfusion, and ensuring a stress-free environment with the judicious use of sedatives made surgery relatively safe in these cases.     

Synthesis of some novel substituted purine derivatives as potential anticancer, anti-HIV-1 and antimicrobial agents

In search of novel purine antimetabolites, a series of 8-substituted methylxanthine derivatives was prepared in order to explore their in vitro anticancer, anti-HIV-1 and antimicrobial activities. The target compounds include: 8-[(3-substituted-4-oxo-thiazolidin-2-ylidene)hydrazino]-1,3-dimethyl (or 1,3,7-trimethyl)-3,7-dihydropurine-2,6-diones 5a-e, 8-[(3,4-disubstituted 2,3-dihydrothiazol-2-ylidene)hydrazino]-1,3,7-trimethyl-3,7-dihydropurine-2,6-diones 6a-d and 8-(5-amino-3-arylpyrazol-1-yl)-1,3-dimethyl- (or 1,3,7-trimethyl)-3,7-dihydropurine-2,6-diones 7a-g. The in vitro anticancer results revealed that compound 5d exhibited a super sensitivity profile towards leukemia K-562 with a GI(50) value of <0.01 microM. Compound 7c showed significant activity against colon cancer HCT-15 and renal cancer CAKI-1 (GI(50) values of 0.47 and 0.78 microM, respectively). Compound 7a displayed high activity against colon cancer HCT-15 (GI(50 )= 0.8 microM). The anti-HIV-1 results indicated that compound 6b displayed a good reduction of viral cytopathic effect (56.69%). The antimicrobial results showed that compound 5a was four times more active than ampicillin against P. aerugenosa (MIC =or< 25 microg/mL), compound 5b had twice the activity of ampicillin, while compounds 5d, 7c and 7f were equipotent to ampicillin. On the other hand, compound 7a was equipotent to ampicillin against P. vulgaris (MIC = 50 microg/mL).     

Statistical issues for HIV surrogate endpoints: point/counterpoint

This paper summarizes the proceedings of an NIAID-sponsored workshop on statistical issues for HIV surrogate endpoints. The workshop brought together statisticians and clinicians in an attempt to shed light on some unresolved issues in the use of HIV laboratory markers (such as HIV RNA and CD4+ cell counts) in the design and analysis of clinical studies and in patient management. Utilizing a debate format, the workshop explored a series of specific questions dealing with the relationship between markers and clinical endpoints, and the choice of endpoints and methods of analysis in clinical studies. This paper provides the position statements from the two debaters on each issue. Consensus conclusions, based on the presentations and discussion, are outlined. While not providing final answers, we hope that these discussions have helped clarify a number of issues, and will stimulate further consideration of some of the highlighted problems. These issues will be critical in the proper assessment and use of future therapies for HIV disease. © 1998 John Wiley & Sons, Ltd.     

Validity of stroke diagnosis on hospital discharge records in Saskatchewan, Canada: implications for stroke surveillance.

This study examines the validity of the diagnosis of stroke on hospital discharge records in Saskatchewan, Canada. In total, 1,494 records with a discharge diagnosis of 'stroke' or a 'stroke-related condition' were reviewed. The clinical algorithm of the 1980 USA National Survey of Stroke was considered the 'gold standard'. The positive predictive value of a primary diagnosis of stroke in the tertiary-care hospitals was about 90%. In community hospitals the majority of stroke cases were coded as ICD9 436 in which the positive predictive value was 78%. The variation between regions would limit the use of hospital discharge data for stroke surveillance.     

Improving Breastfeeding Environments and Feeding Practices in Family Child Care Homes with the Go NAP SACC Program

Maternal and Child Health Journal - Breastfeeding and responsive feeding are important practices that support the health of infants and women. In the United States, breastfeeding continuation rates...     

Novel benzimidazoles with potential antimicrobial and antineoplastic activities

The synthesis of some substituted 4-[1-(1-(1H-benzimidazol-2-yl) alkylamino]-1,5-dihydro-2H-pyrrol-2-ones and 3-[1-(1H-benzimidazol-2-yl)alkyl]-2-substituted-4(3H)-quinazolinon es is described. Five compounds displayed in vitro antibacterial and antifungal activities. Three of these compounds were tested against P-388 lymphocytic leukemia in mice and were inactive.     

Allergy in systemic lupus erythematosus. IgE levels and reaginic phenomenon

Twenty-seven patients with systemic lupus erythematosus (SLE) were investigated for the presence of allergic reactivity, and serum IgE levels were measured by immunoassay. Compared to controls, SLE patients had significant increases of only allergic rhinitis and drug allergy. Despite the usual hyperimmunoglobulinemia in SLE, IgE levels were not elevated (mean: 251 IU). Because recent reports have noted elevated IgE in rheumatoid arthritis, this finding may suggest basic immunologic differences between rheumatoid arthritis and SLE.     

TREM-1 orchestrates angiotensin II–induced monocyte trafficking and promotes experimental abdominal aortic aneurysm

The triggering receptor expressed on myeloid cells 1 (TREM-1) drives inflammatory responses in several cardiovascular diseases but its role in abdominal aortic aneurysm (AAA) remains unknown. Our objective was to explore the role of TREM-1 in a mouse model of angiotensin II–induced (AngII–induced) AAA. TREM-1 expression was detected in mouse aortic aneurysm and colocalized with macrophages. Trem1 gene deletion (Apoe^–/–Trem1^–/–), as well as TREM-1 pharmacological blockade with LR-12 peptide, limited both AAA development and severity. Trem1 gene deletion attenuated the inflammatory response in the aorta, with a reduction of Il1b, Tnfa, Mmp2, and Mmp9 mRNA expression, and led to a decreased macrophage content due to a reduction of Ly6C^hi classical monocyte trafficking. Conversely, antibody-mediated TREM-1 stimulation exacerbated Ly6C^hi monocyte aorta infiltration after AngII infusion through CD62L upregulation and promoted proinflammatory signature in the aorta, resulting in worsening AAA severity. AngII infusion stimulated TREM-1 expression and activation on Ly6C^hi monocytes through AngII receptor type I (AT₁R). In human AAA, TREM-1 was detected and TREM1 mRNA expression correlated with SELL mRNA expression. Finally, circulating levels of sTREM-1 were increased in patients with AAA when compared with patients without AAA. In conclusion, TREM-1 is involved in AAA pathophysiology and may represent a promising therapeutic target in humans.