Under-reporting of sputum smear-positive tuberculosis cases in Kenya.

BACKGROUND: Although an estimated three million tuberculosis (TB) cases worldwide are missed by national TB programs annually, the level of under-reporting of diagnosed cases in high TB burden settings is largely unknown. OBJECTIVE: To quantify and describe under-reporting of sputum smear-positive TB cases in Kenya. DESIGN: A national-level retrospective TB inventory study was conducted. All sputum smear-positive TB cases diagnosed by public or private laboratories during 1 April-30 June 2013 were extracted from laboratory registers in 73 randomly sampled subcounties and matched to TB cases in the national TB surveillance system (TIBU). Bivariate and multivariate analyses were conducted. RESULTS: In the subcounties sampled, 715 of 3409 smear-positive TB cases in laboratory registers were not found in TIBU. The estimated level of under-reporting of smear-positive TB cases in Kenya was 20.7% (95%CI 18.4-23.0). Under-reporting was greatest in subcounties with a high TB burden. Unreported cases were more likely to be patients aged ⩾55 years, have scanty smear results, and be diagnosed at large facilities, private facilities, and facilities in high TB burden regions. CONCLUSION: In Kenya, one fifth of smear-positive TB cases diagnosed during the study period went unreported, suggesting that the true TB burden is higher than reported. TB surveillance in Kenya should be strengthened to ensure all diagnosed TB cases are reported.

Burden of tuberculosis in indigenous peoples globally: a systematic review.

BACKGROUND: The burden of tuberculosis (TB) in the estimated 370 million indigenous peoples worldwide is unknown. OBJECTIVE: To conduct a literature review to summarize the TB burden in indigenous peoples, identify gaps in current knowledge, and provide the foundation for a research agenda prioritizing indigenous health within TB control. METHODS: A systematic literature review identified articles published between January 1990 and November 2011 quantifying TB disease burden in indigenous populations worldwide. RESULTS: Among the 91 articles from 19 countries included in the review, only 56 were from outside Australia, Canada, New Zealand and the United States. The majority of the studies showed higher TB rates among indigenous groups than non-indigenous groups. Studies from the Amazon generally reported the highest TB prevalence and incidence, but select populations from South-East Asia and Africa were found to have similarly high rates of TB. In North America, the Inuit had the highest reported TB incidence (156/100000), whereas the Metis of Canada and American Indians/Alaska Natives experienced rates of <10/100000. New Zealand's Maori and Pacific Islanders had higher TB incidence rates than Australian Aborigines, but all were at greater risk of developing TB than non-indigenous groups. CONCLUSION: Where data exist, indigenous peoples were generally found to have higher rates of TB disease than non-indigenous peoples; however, this burden varied greatly. The paucity of published information on TB burden among indigenous peoples highlights the need to implement and improve TB surveillance to better measure and understand global disparities in TB rates.

The natural history of early recurrent carotid artery stenosis.

BACKGROUND: Early recurrent carotid stenosis, defined as greater than 50% stenosis within 2 years of a carotid endarterectomy (CEA), occurs in 4% to 19% of patients. These lesions are secondary to myointimal hyperplasia (MH). The natural history of these lesions has been examined prospectively, but the appropriate management of these lesions has not been clearly defined. The vascular surgery service at Madigan Army Medical Center (MAMC) has prospectively collected a cohort of patients with recurrent high-grade carotid stenoses following CEA to determine their natural history and define the ideal therapeutic approach for those lesions. METHODS: Patients undergoing CEA between January 1, 1993, and January 1, 1997, at a single tertiary care institution were followed prospectively with postoperative carotid duplexes at 3-month intervals for the first year and then every 6 months for a year and then annually thereafter. Data were collected regarding patient demographics, type of carotid closure, neurologic morbidity, and death. These results were compared with accepted rates in the literature. Discrete variables were tested for significance by chi-square analysis and Fisher's exact test. A P value less than or equal to 0.05 was considered significant. RESULTS: One hundred and seventy-four (174) patients with 181 operative sites were evaluated. Fourteen patients with 17 sites (9%) had recurrent stenosis. Twelve patients with 14 sites (7%) had stenoses of 50% to 79%. All were asymptomatic. Two patients with 3 sites (2%) had stenoses greater than 80%. Two sites were managed operatively because of neurologic symptoms or preocclusive nature and one remains asymptomatic and stable on serial duplex imaging. All lesions were present at 6 months and those in the 50% to 79% category did not progress in follow-up. Recurrent carotid stenosis occurred to a significantly higher degree in women (women 11 of 60 18.3% versus men 6 of 114 5.3%; P = 0.25), primary closure versus patch angioplasty (primary 6 of 22 27.3% versus patch 11 of 159 6.9%; P = 0.01), and dacron versus polytetrafluoroethylene (PTFE) patch angioplasty (dacron 7 of 36 19.4% versus PTFE 2 of 100 2.0%; P = 0.02). CONCLUSION: Early recurrent stenosis (50% to 79%) is a benign lesion. Patch angioplasty is preferred over primary closure. Dacron patches had a significantly higher rate of recurrent stenosis when compared with PTFE patches. Women undergoing CEA are more prone to recurrent stenosis. Postoperative duplex at 3 and 6 months will identify recurrent carotid stenosis (given a normal duplex prior to discharge following CEA). Moderate high-grade (50% to 79%) stenoses are benign. High-grade (80% to 99%) stenoses require individual management.

Duplex-guided compression of iatrogenic femoral pseudoaneurysms.

BACKGROUND: Iatrogenic pseudoaneurysms are a major complication following percutaneous cannulations of the femoral artery. Surgical repair has been the traditional treatment modality. Recent reports have introduced duplex-guided compression as a means of nonoperative management of these injuries. We proposed to determine if duplex-guided compression of femoral pseudoaneurysms could be successfully performed, could be done without complication, and could maintain thrombosis on long-term follow-up. STUDY DESIGN: All patients presenting with large groin hematomas following invasive percutaneous femoral artery procedures over a seven-month period were studied using color-flow duplex analysis. Six pseudoaneurysms were discovered and successfully treated with duplex-guided compression. All patients were then followed-up prospectively with both early and long-term repeat duplex analysis. RESULTS: All patients were rescanned 72 hours later and the pseudoaneurysms remained thrombosed. Upon returning for long-term follow-up examination, patients again had duplex confirmation of thrombosis, with a mean follow-up time of 21 months (range, five to 29 months). No complications attributable to this technique have been noted. CONCLUSIONS: This study confirms the clinical usefulness of duplex-guided compression in the evaluation and treatment of iatrogenic femoral pseudoaneurysms.

Intraoperative determination of intestinal viability by pulse oximetry.

The utility of transserosal photoplethysmographic pulse oximetry (PO) to assess intestinal viability intraoperatively was evaluated using an experimental canine model. Comparisons of PO were made with continuous-wave Doppler ultrasound (CWDU) and fluorescein (FL) using histopathologic examination for control. Clinical examination estimates were included for reference. Four 20 cm portions of small bowel from each of four dogs were made ischemic by mesenteric ligation. Thus 320 individual 1 cm bowel segments were studied by means of PO, CWDU, FL, and control histologic grading for ischemia. Statistical analysis revealed no significant differences, with PO matching CWDU and FL in intraoperative assessment of small bowel viability. PO, which is readily available in most operating rooms, is a simpler method than CWDU or FL for assessing intestinal viability. This technique is operator independent, easy to interpret and repeat, and is well tolerated. PO is the preferred alternative for objective intraoperative assessment of intestinal viability.

Natural history of atherosclerotic renal artery stenosis associated with aortic disease.

The natural history of atherosclerotic renal artery stenosis has not been well defined, particularly when discovered in conjunction with aortic disease requiring correction. To better define the natural history of such lesions, 194 sequential aortograms in 48 patients were studied to define predictive criteria for stenoses at risk for progression. Sixty-six unsuspected atherosclerotic renal arterial stenoses were identified on the initial aortograms. Disease progressed in 42 arteries (53%), 14 bilateral and 28 unilateral. Seven arteries developed occlusion. All had stenoses averaging 80% (range 61% to 94%) noted on the most recent aortogram preceding occlusion. Risk factors including smoking, diabetes mellitus, elevated serum lipids, coronary artery disease, peripheral arterial disease, or change in blood pressure or creatinine, did not correlate with degree or rate of progression of the renal artery stenosis. A difference in kidney size, although varying inversely with degree of stenosis, was not a statistically significant marker of disease progression. This analysis suggests that identification of renal arterial stenoses that will progress is best determined by sequential aortography. Highly stenotic vessels are more prone to occlude than those less stenotic. Consequently, individuals with preocclusive lesions should benefit from prophylactic renal revascularization during aortic reconstruction.

Left flank retroperitoneal exposure: a technical aid to complex aortic reconstruction.

Over the last 5 years an extended left flank retroperitoneal approach was used in 85 of 531 (16%) aortic reconstructions deemed technically complex. Abdominal aortic aneurysm repair was performed in 70 patients (82%), bypass of aortoiliac occlusive disease was performed in 11 (13%), and aortic endarterectomy for mesenteric and/or renovascular disease was performed in 4 (5%). Indications for use of this approach included a "hostile" abdomen (43 patients), juxta/suprarenal abdominal aortic aneurysm (35), large (greater than 10 cm) abdominal aortic aneurysm (12), extreme obesity (10), associated renal and/or visceral artery stenosis requiring endarterectomy (9), inflammatory abdominal aortic aneurysm (2), and horseshoe kidney (2). Suprarenal or supraceliac aortic clamping, averaging 31 minutes, was required in 43 patients (50%). Postoperative recovery was rapid (average length of stay, 10.2 days), and morbidity was minimal despite the complex nature of these reconstructions. The perioperative mortality rate in elective operations was 1.2%. This approach facilitated proximal abdominal aortic exposure and anastomosis, especially in large, pararenal aneurysms or in situations unfavorable to a transabdominal approach. Whereas a left flank retroperitoneal approach can be used in most aortic reconstructions, it seems especially suited to those that pose significant technical challenges.

Binding of phosphonate chelating agents and pyrophosphate to apotransferrin.

Difference ultraviolet spectroscopy has been used to monitor the binding of a series of phosphonate ligands to human apotransferrin. The ligands consist of pyrophosphate as well as the phosphonic acids (aminomethyl)phosphonic acid (AMPA), (hydroxymethyl)phosphonic acid (HMP), (phosphonomethyl)-iminodiacetic acid (PIDA), N,N-bis(phosphonomethyl)glycine (DPG), and nitrilotris(methylenephosphonic acid) (NTP). Equilibrium constants have been measured for the sequential binding of two ligands per molecule of apotransferrin. In addition, site-specific equilibrium constants have been measured for the binding of AMPA, HMP, and PIDA to the vacant binding site of both forms of monoferric transferrin. Since titrations of diferric transferrin produce no difference UV spectrum, it is proposed that the primary binding site for phosphonic acids includes the protein groups that bind the synergistic bicarbonate anion that is required for formation of a stable ferric transferrin complex. It is further proposed that those ligands with two phosphonate groups can simultaneously bind to cationic amino acid side chains that extend into the cleft between the two domains of each lobe of transferrin. From an inspection of the ferric transferrin crystal structure, the most likely anion binding residues in the cleft are Arg-632 and Lys-534 in the C-terminal lobe and Lys-206 and Lys-296 in the N-terminal lobe.

Site selectivity in the binding of inorganic anions to serum transferrin.

Equilibrium constants for the sequential binding of two anions at the specific metal-binding sites of apotransferrin have been measured by difference ultraviolet spectroscopy in 0.1 M N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes) at pH 7.4 and 25 degrees C. Log K1 values for phosphate, phosphite, sulfate, and arsenate fall in the narrow range of 3.5-4.0, while the log K1 for bicarbonate is 2.73. No binding is observed for nitrate, perchlorate, or borate. A dinegative charge appears to be the most important criterion for anion binding. Equilibrium constants have also been measured for binding of anions to both forms of mono(ferric)transferrin. There appears to be a very small site selectivity (0.2 to 0.4 log units) for phosphate, arsenate, and phosphite that favors binding to the N-terminal site, but there is no detectable selectivity for binding of sulfate or bicarbonate. Comparison of the binding affinities and anion selectivity with literature data on anion-binding to protonated macrocyles and cryptates strongly supports the existence of specific anion-binding sites on the protein. Binding constants were also measured in 0.01 M Hepes. The anionic sulfonate group of the buffer appears to have a small effect on anion binding.

Protein C deficiency. A cause of unusual or unexplained thrombosis.

Familial hypercoagulable states are a collection of syndromes characterized by an inherited deficiency of various proteins involved in the control of coagulation and include antithrombin III, plasminogen, protein C, and protein S. Affected patients usually develop venous thrombosis as adults. During a 15-month interval, we identified five patients with venous thrombosis accompanied by protein C deficiency. Four patients presented with deep venous thrombosis, which was recurrent in two, and one patient developed mesenteric venous thrombosis. The kindred of this last patient suggested an autosomal dominant genetic transmission of protein C deficiency. Patients' ages at the time of diagnosis of disease ranged from 28 to 41 years. All patients had low levels of protein C (range, 34 to 67 U/dL; normal, 70 to 130 U/dL). All patients were treated with heparin sodium immediately and then given long-term oral anticoagulation therapy with warfarin sodium. Protein C deficiency is a predisposing factor to the development of venous thrombosis that has only recently been recognized. Treatment of symptomatic protein C deficiency requires short-term heparin therapy followed by long-term oral anticoagulation therapy with warfarin. Oral anticoagulation treatment must be initiated slowly with no loading dose to avoid warfarin-associated skin necrosis. Patients with unexplained or unusual thrombosis, especially if it occurs at an early age, and patients with recurrent episodes of lower limb venous thrombosis should have their protein C levels measured. If a deficiency is documented, long-term warfarin anticoagulation therapy is recommended.

Surface biofilm disruption. Enhanced recovery of microorganisms from vascular prostheses.

Ultrasonic oscillation (sonication) of explanted vascular prosthetic graft material can disrupt surface biofilms and increase the recovery of adherent microorganisms. Recovery of microorganisms from vascular grafts was studied in a canine model of Staphylococcus epidermidis graft contamination (N = 26) and on graft material excised from patients undergoing femoral anastomotic pseudoaneurysm repair (N = 7). Surface biofilm disruption by sonication significantly increased the incidence of positive cultures of excised graft material compared with broth (P less than .010) and blood agar plate (P less than .005) culture techniques. The S epidermidis was recovered from 31% of the canine vascular grafts and 100% of the clinical specimens. The in vitro production of a glycocalyx "slime" was demonstrated in 73% of the recovered staphylococcal strains. The formation of an adherent bacteria biofilm on implanted vascular prostheses is not an uncommon occurrence and is an important factor in the pathogenesis of anastomotic pseudoaneurysm formation and late graft infection.