Mission to the West Indies

A population medical genetic study of spinal muscular atrophies (SMA) was carried out in 1800 individuals in 6 russian and 3 middle asian regions. 33 patients with SMA were ascertained including 29 with autosomal recessive childhood proximal SMA (SMA I-III) and 4 patients with rare SMA types. There were revealed either overlapping of diagnostic criteria of I-III types in some patients or interfamilial differences of types in 3 from 6 familial cases, (one of them with distant relatives affected as well as pronounced clinical genetic variability of rare forms of SMA (all sporadic cases).     

Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems

A 31-year-old female was found dead with 18 nicotine transdermal system patches taped to her upper body and a plastic bag taped over her nose and mouth (the cause of death was ruled asphyxiation). Nicotine concentrations in biological fluids and tissues were analyzed using a liquid-liquid extraction followed by injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen-phosphorus detector. Cotinine was separated from the biological matrices using solid-phase extraction followed by analysis on an HP-5890 GC with flame ionization detection. A variety of specimens were analyzed, including blood, urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times, respectively, the mean C(max) value reported following the proper administration of a single 7-mg/day patch.     

Comparison of technetium-99m-ECD to Xenon-133 SPECT in normal controls and in patients with mild to moderate regional cerebral blood flow abnormalities

Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range.     

Natural history of adhesional small bowel obstruction: counting the cost

BACKGROUND: The aim of this study was to identify patients admitted with adhesional obstruction to determine if there was an identifiable pattern to the type of initial operation, the type of treatment used for the obstructive episode and the subsequent need for further treatment. METHODS: Patients with adhesional obstruction were identified retrospectively in a cross-sectional study using ICD codes relating to admissions in the years 1990 to 1996. The case notes were used to assess their outcome. RESULTS: Fifty-nine case notes from a total of 175 identified initially satisfied the inclusion criteria. These patients had a mean age at presentation of 51 (range 16-88) years and had undergone a total of 122 operations. Thirty-one patients (53 per cent) had a single previous operation with a median time to presentation with obstruction of 5.5 years (range 11 days to 34.7 years); 33 patients (56 per cent) were treated conservatively on their first admission. There was no statistically significant difference in the outcome in patients who received either conservative or surgical treatment. The length of stay in patients treated surgically (median 11 (range 2-47) days) was significantly longer than that for those treated conservatively (median 6 (range 1-39) days) (P< 0.001). A flow chart was constructed demonstrating the eventual outcome of the patients in the study, enabling the cost of adhesional obstruction to be calculated. CONCLUSION: This type of approach could be used to assess the potential effect of different treatment strategies for adhesional obstruction.     

Expression of the POU transcription factor Brn-5 is an early event in the terminal differentiation of CNS neurons

OBJECTIVE: To evaluate transesophageal echocardiography (TEE) as an intraoperative monitoring modality and to assess its safety, reliability, and overall utility in real-time use during cardiac surgery. DESIGN: Prospective, observational cohort study performed from January 1993 to June 1997. SETTING: Operating room of a tertiary care hospital for cardiology and cardiovascular surgery. PARTICIPANTS: Five thousand and sixteen adult patients with acquired heart disease, who underwent 1,356 valve procedures and 3,660 coronary artery bypass graftings (CABGs). INTERVENTIONS: All patients were monitored with radial artery and pulmonary artery catheters, along with continuous TEE monitoring with a multiplane transducer. MEASUREMENTS AND MAIN RESULTS: Prebypass imaging yielded unsuspected findings that either helped or modified the surgical plan in 158 of 1,356 valve procedures (11.65%) and in 993 of 3,660 CABGs (27.13%). There were 3,217 TEE-guided hemodynamic interventions in 944 patients (25.79%) in the CABG group and 629 in 142 patients (10.47%) in the valve group. TEE was the sole guiding factor in initiating therapy in 23.53% of events, whereas it was supportive to other monitoring modalities in 76.46% of events. Postbypass TEE identified the need for graft revision in 29 patients (0.8%), intra-aortic balloon pump (IABP) requirement in 29 patients (0.8%), and inadequate valve repair in 28 patients (2.08%). For the entire series, 38.78% of patients benefited from prebypass and 39.16% from postbypass use of TEE. There were no complications attributable to the use of TEE in the entire series. There was 87% concordance between online interpretation by a trained anesthesiologist and offline analysis by a cardiologist. CONCLUSION: Intraoperative TEE is useful in formulating the surgical plan, guiding various hemodynamic interventions, and assessing the immediate results of surgery. It is safe and the results are reliable in the hands of trained anesthesiologists.     

Mapping of specific and promiscuous HLA-DR-restricted T-cell epitopes on the Plasmodium falciparum 27-kilodalton sexual stage-specific antigen

We have characterized HLA-DR-restricted T-cell epitopes on the 27-kDa protein (Pfg27), a sexual stage-specific antigen, of the human malaria parasite Plasmodium falciparum in subjects with a history of malaria. Pfg27, expressed early in the sexual stages, is recognized by monoclonal antibodies capable of reducing the infectivity of gametocytes in mosquitoes. By using 16 Pfg27-specific CD4(+)-T-cell clones derived from three donors, seven different T-cell epitopes were identified. Among them, P11 (amino acids 191 to 210 of the Pfg27 sequence, IDVVDSYIIKPIPALPVTPD) was found to contain a previously described binding motif for multiple HLA-DR allotypes. Indeed, P11 was found to be promiscuous in that it could be recognized by T cells in the context of at least five different HLA-DR molecules. The cytokine profile of the clones was mixed. Seven of nine T-cell clones exhibited a Th0-like cytokine profile, producing high levels of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) upon stimulation with specific peptides and mitogens. The other two clones had a Th1-like cytokine profile with high expression of IFN-gamma and no IL-4. Identification of a promiscuous epitope in Pfg27 could play a significant role in the design of a subunit vaccine for suppressing malaria transmission.