published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Community Medicine / Master / Master of Public Health

Use of appropriate footwear among diabetics and those with diabetic foot problems has been well documented to play a vital role in the prevention and treatment of established foot disease. The incidence and prevalence rates of diabetes in Africa are increasing and foot complications are rising parallel. Nigeria is Africa’s most populous nation which also has the highest number of people (up to 3 million) suffering with diabetes in the continent. This is related to the lifestyle of the people which is changing including diet. Many urbanites are embracing Western way of living. There is however lack of adequate knowledge about the role of footwear in the management of foot related problems among diabetic patients in the country. This study is the first of its kind to be done in Nigeria with an aim to develop a framework that would help to identify appropriate footwear materials and designs for people suffering with diabetes. To achieve this, data were collected through questionnaire and interview surveys, shoe upper materials analysis and foot measurements. In addition, Product Design Specification (PDS) and design framework were formulated. And functional footwear prototypes were designed, constructed and assessed. The data from the questionnaire survey indicate that up to 75% of the diabetic subjects have not received information about the type of footwear they should wear most often. The study revealed that the patients have very poor knowledge about diabetes and its complications, foot care, and the use of appropriate footwear. It was discovered that up to 53% female and 37% male of the patients were wearing slippers most often. Similarly, the findings from the medical doctors interviewed show that up to 66% of the patients were wearing slippers or slip-on (with no fastening mechanism) most often. The research revealed that financial constraint was a key factor to use of appropriate footwear by the patients. Many use cheap footwear regardless whether they provide the required protection and comfort to their feet or not. It was found out that specialist knowledge among medical doctors regarding foot care and provision of special footwear like orthopaedic and diabetic footwear to patients was very low. The shoe upper materials analyses demonstrated that leather has good physical properties required for making diabetic footwear. Data from the measurement of feet indicated that no individual’s feet are exactly the same even as people wearing the same shoe size might not have the same foot dimensions. It was concluded that these differences could have considerable effects on the shoe wearer. From the measured values, the tolerable allowance was found to be 3.4mm and 3.5mm for male and female subjects respectively. The fitting and comfort assessment of the prototypes have shown that some parts of the last used to make the prototypes would require amendments in order to accommodate minor foot deformities properly. The findings from the research were used to develop PDS and a research framework which could be used as a guide for diabetic footwear design and construction. Finally, the contributions of this research to knowledge and critical areas that would require further investigations were outlined.

Approved for public release; distribution is unlimited / The connection between eye disease and diabetes is proven and is no longer a point of conjecture. In focusing attention on the retina, profound inroads have been made in the fight against this dreaded disorder of the blood. By carefully imaging the blood vessels in the eye, medical professionals can make accurate diagnoses based upon the changes and abnormalities observed. In addition, because the vasculature in the retina is extremely sensitive to fluctuations in normal bodily processes, often the first indication of diabetes and many other diseases manifest themselves here and are found during routine eye examinations. This thesis will explore the possibilities of a new method of retinal imaging by the blending and application of existing technologies. With the use of an automated, infrared-based imaging system, problems related to human error and the limitations of existing methods can be readily resolved and the groundwork can be laid for a new standard of accuracy in retinal imaging. Most importantly, it will automate the entire procedure providing medical specialists heretofore unavailable accuracy in their diagnoses. / http://archive.org/details/functionalspecif00domb / Lieutenant, United States Navy

Class of 2010 Abstract / OBJECTIVES: To evaluate glycemic control, therapy associated weight loss/gain, and hypoglycemic events for the newer type 2 diabetic agents pramlintide, exenatide, and sitagliptin. METHODS: The meta-analysis examined the efficacy of three currently FDA approved peptide analogues in nonpregnant adults with type 2 diabetes mellitus. All randomized, placebo controlled trials of exenatide, pramlintide, and sitagliptin that were indexed in MEDLINE or and the Cochrane Database of Systematic Reviews that fit the inclusion criteria were included. The drug treatment efficacy was analyzed in terms of HbA1c (glycosylated hemoglobin) change from baseline compared to placebo in trials lasting at least 12 weeks. Weight change from baseline per treatment group was also a primary measure. The safety of the treatments was assessed in terms of number of hypoglycemic events noted in the clinical trials. Each of these dependent variables was assessed separately for the three products. RESULTS: The meta-analysis of the six exenatide articles included in the analysis found statistically significant reductions in both HbA1c and weight when compared to placebo. However, patients were three times as likely to experience hypoglycemia with exenatide than placebo (RR= 3.01 95%CI[0.427 to 3.865]). Meta-analysis of pramlintide studies showed statistically significant lowering of HbA1c and weight. Overall pramlintide resulted in a rate of hypoglycemia nearly equal to that of placebo (RR= 0.94 95%CI[0.699 to 1.265]). Meta-analysis of sitagliptin found statistically significant reductions in HbA1c compared to placebo. However, sitagliptin use was not associated with a reduction in weight in the random effects meta-analysis model. In terms of hypoglycemic events, sitagliptin use was associated with 2.89 times greater risk of causing hypoglycemic episodes compared to placebo (RR=2.89 95%CI[0.704 to 5.877]). CONCLUSIONS: All three newer products were associated with improved glycemic control compared to placebo. Improvement in weight was associated with exenatide and pramlintide treatment. Pramlintide was not associated with an increase in hypoglycemic episodes.

Class of 2007 Abstract / Objectives: To determine the effect of antihypertensive use on renal function and other diabetic complications in adults over the age of 18 with type 2 diabetes mellitus (DM). Methods: A retrospective secondary analysis of the NIH Pima epidemiologic data included 1,828 individuals with type 2 DM were evaluated for antihypertensive use and DM complications. Statistical analysis was done using general linear model regression (GLM) or logistic regression models controlling for age, sex and DM duration. Three groups were established to evaluate antihypertensive use Group 1 those taking antihypertensives to those not taking antihypertensives, Group 2 those taking more than one (multiple) antihypertensives to those only taking one and Group 3 those taking an angiotensin converting enzyme (ACE) inhibitor to those not taking an ACE. Results: Group 1 those taking antihypertensives were significantly worse for all outcome measures than those taking no antihypertensives as evident with: renal function (ACR 43 mg/mmol versus 15.9 mg/mmol (ρ=0.0003) and albuminuria 55.8% versus 37.6% (p=0.0039), retinopathy, neuropathy and CVD. Group 2 those taking multiple antihypertensives had significantly worse renal function (ACR 69.2 mg/mmol versus 34.5 mg/mmol (p=0.0329) and albuminuria 63% versus 52% (p=0.0396)), CVD while retinopathy and neuropathy were not significantly different. Group 3 those taking ACE had significantly worse renal function (ACR 43.8 mg/mmol versus 35.2 mg/mmol (p=0.0329)) while CVD was improved and no difference was observed in retinopathy and neuropathy. Conclusions: Antihypertensive use had little impact on preventing diabetic complications. This is contrary to well- documented literature that supports the use of antihypertensives to slow disease progression and protect renal function.

L’ostéite du pied diabétique (OPD) est une complication survenant à la suite d’une plaie située sous les malléoles chez un patient diabétique. L’OPD survient à la faveur d’une plaie généralement chronique du pied favorisée par la neuropathie e/ou l’artérite des membres inférieurs fréquemment associées au diabète. Il s’agit bien d’une ostéite et non d’une ostéomyélite car l’origine hématogène de l’OPD n’est pratiquement pas décrite. L’OPD est une affection dont l’incidence augmente régulièrement avec l’évolution du diabète dans le monde. On estime en effet que 15 à 25% des patients diabétiques présenteront à un quelconque moment de leur existence une ulcération du pied qui subira une infection dans 40 à 80% des cas. L’OPD retarde la cicatrisation des plaies qui ont conduit à sa survenue et augmente significativement le risque d’amputation mineure ou majeure. C’est, avec l’artérite des membres inférieurs, l’une des grandes causes d’amputation d’un membre inférieur chez les patients diabétiques. L’OPD est avant tout une infection ostéo-articulaire qui survient sur un terrain particulier. L’altération des défenses immunitaires systémiques et locales, quoique variables d’un sujet diabétique à un autre, réduit les chances de guérison de l’OPD. S’agissant d’une infection ostéo-articulaire chronique le plus souvent staphylococcique survenant sur un terrain fragilisé il a longtemps été estimée que la guérison ne pouvait être espérée sans la suppression du tissu ostéo-articulaire infecté, en pratique sans amputation. L’amputation n’est cependant pas sans conséquence fonctionnelle et » l’épargne ostéo-articulaire » a été prônée ces dernières années sous deux formes : la résection ostéo-articulaire suspendue ou « amputation fonctionnelle » et le traitement purement médical faisant appel principalement aux antibiotiques. Le traitement médical de l’OPD a l’avantage de n’entraîner aucune lésion anatomique du pied. Il a l’inconvénient de faire appel à des molécules antibiotiques réputées efficaces dans le contexte particulier d’infection ostéo-articulaire chronique qui ont pour la plupart des molécules un effet de pression de sélection de la résistance bactérienne élevé et pour la plupart un potentiel toxique majoré par les co-morbidités fréquemment observées chez ces patients. En considérant les règles généralement admises pour le traitement des infections ostéo-articulaires, il apparait que le choix des antibiotiques doit idéalement être fondé sur les données de la culture d'un fragment osseux. Ceci représente cependant une approche nouvelle pour le traitement antibiotique de l'OPD. Nous montrerons dans ce travail les résultats de travaux publiés suggérant que:1) la biopsie osseuse transcutanée est une technique dénué de risque et actuellement la seule technique permettant une documentation fiable de l’OPD et que les prélèvements obtenus par écouvillonnage ou par ponction-aspiration ne peuvent être utilisés en remplacement de la biopsie osseuse (articles 1 et 2)2) les patients traités médicalement pour OPD ont plus de chance de guérir lorsque le traitement est fondé sur les résultats d'une biopsie osseuse (article 3) nque sur ceux de prélèvements superficiels3) la biopsie osseuse transcutanée n'est actuellement pratiquement pas utilisée dans la majorité des centres Français du pied diabétique. Enfin, nous présenterons les projets de 3 études sur le sujet de la biopsie osseuse en cours ou qui seront développées dans les mois à venir. / Diabetic foot osteomyelitis (DFO) is a complication of a foot wound located under malleoli. DFO usually occurs as a consequence of a chronic foot wound and is facilitated by neuropathy and peripheral vascular disease (PVD) which are both frequently associated with diabetes. OPD is rather an osteitis than an osteomyelitis as a hematogenous origin of DFO is almost not reported. DFO is an increasing worldwide problem which is related to the increasing number of patients with diabetes in the world. It is generally admitted that 15 to 25% of all patients with diabetes will experience a foot wound during their lifetime and that 40 to 80% of them will be infected. DFO has a deleterious effect on the wound healing and is associated with an enhanced risk for relapsing infection of the foot. DFO is with PVD a major cause for both minor and major limb amputations in these patients. DFO is first of all a bone and joint infection that occurs in a patient with diabetes. Complications of advanced diabetes mellitus like microvascular abnormalities and phagocytosis defects are likely to reduce the chance of healing. As most DFO are due to Staphylococcus aureus and that most of these patients have comorbidities, it has generally been thought that bone removal was required in order to obtain a complete healing. Minor amputation may however result in biomechanic disorders of the foot and subsequently may lead to new episodes of foot wound thus new DFO episodes. As a consequence, some authors have proposed to perform limited bone resections (i.e. without ray or toe amputation) or to use a medical approach of DFO (i.e. based on antibiotic therapy only). Medical treatment of DFO has the advantage to avoid the development of biomechanic alterations of the foot. However, given the high potential for selecting bacterial resistance of antimicrobial agents like rifampin and fluoroquinolones, it appears that the choice of the antibiotics to use should be best based on the microbiological testing of a bone culture which is consistent with the basic rules widely admitted for the medical treatment of any other bone and joint infections. This represents, nevertheless, a new approach of the treatment medical treatment of DFO. We will present in the present document the results of personal studies that suggest that 1) bone biopsy is a safe procedure and is currently the best method for obtained a reliable microbiological documentation of DFO and, in particular, that both swabs and needle aspiration cannot be used a surrogate tools for determining the pathogens involved in DFO (articles 1 and 2). 2) patients with DFO treated medically have a better chance to heal when the antibiotic therapy is guided by the results of a bone biopsy than when it is guided by superficial sample results (-article 3)3) bone biopsy is not used routinely used in most French diabetic foot centers (article 4). Finally, we will present 3 projects of study that are currently on process or will be developed in the next future.

Submitted in fulfillment of the requirements for the degree of Master of Clinical Technology (Nephrology), Durban University of Technology, Durban, South Africa, 2013. / Diabetic nephropathy is a serious complication of diabetes that can lead to end stage renal failure (ESRF). It is now the most common cause of ESRF in patients accepted onto renal replacement therapy (RRT) programmes. Kidney disease is common in South Africa. 60-65% is due to inherited hypertension and 20-25% due to Type 2 diabetes (National Kidney Foundation of South Africa, 2002). The renal replacement therapies include haemodialysis, peritoneal dialysis and transplantation. Successful long-term haemodialysis in patients with end stage renal disease (ESRD) depends to a large extent upon a trouble- free vascular access. Achieving a successful vascular access remains a challenge especially in the diabetic population. Current Kidney Dialysis Outcome Quality Initiative (KDOQI) guidelines encourage placing Arterio-Venous Fistula (AVF) in more haemodialysis patients. While the upper limb is the preferred site for AVF creation, researchers are undecided on which is the ideal location (distal or proximal arm) in the diabetic population. Many new fistulae fail to mature sufficiently to be usable for haemodialysis. Pre-insertion work-up with regard to haemodialysis access is important in maintaining the most appropriate access in the growing diabetic population requiring haemodialysis. Pre-operative vascular mapping to identify suitable vessels has been reported to improve vascular access outcomes . In South Africa, duplex scanning is not routinely done, and a clinical judgement by the surgeon remains in most instances the deciding factor on the site of the AVF. Whilst conducting this research, it has been found that while diabetic patients may have AVF created, the maturation time is of a much extended period, and a challenge to achieve the desired dose of dialysis. This is a prospective, quantitative and qualitative study of 21 diabetic patients. These included patients that were starting on the chronic haemodialysis program and limited to patients that were having first attempt of AVF creation and aims to establish if sonogram testing provides a more accurate measure of the ideal location for the AVF, or if a clinical evaluation alone by the surgeon is sufficient. Surgical techniques are different amongst surgeons and clinical evaluation is more a subjective decision. By limiting the surgeons performing the AVF, a standardized surgical procedure was established. If an ideal AVF access for the patient is created, haemodialysis efficiency is increased and ultimately patient outcome improved. The AVF was created according to the clinical evaluation as is the current process, and the surgeons were not aware of the duplex sonogram results. Failure and success of AVF were analysed according to primary patency and functional success. A primary patency success of the AVF does not guarantee functional success. If an AVF is not able to complete an entire haemodialysis session trouble free at the prescribed dialysis dose, the AVF is considered a failure irrespective of primary patency success. This was evident with 10% of patients who had primary patency but functional success was not achieved. With a 55% functional success in this study with AVF created on clinical evaluation, there was no significance difference (p=0.795) if AVFs were based on duplex sonogram findings. However, there was evidence of increased AVF success in 33% of the failed AVFs when the new AVFs were created at the duplex sonogram site. 95% of patients in this study had commenced haemodialysis with a Central Venous Catheter (CVC). AVF success could be increased if early referral of diabetic patients for permanent access to the surgeon occurred. Maturation rate of AVF differed from KDOQI guidelines with AVF first cannulation only after 17 weeks, and not after the recommended time of 6 weeks. Blood flow rates on dialysis also varied with international standards, with only maximum of 400mls/min reached after one year. With distal arm AVF, diameter of radial artery of less than 2mm and cephalic vein less than 3mm was associated with AVF failure. This research study represents the first of its kind in Kwazulu Natal looking at vascular access sites in diabetic patients with End Stage Renal Disease on haemodialysis. / PDF Full-text unavailable. Please refer to hard copy for Full-text / M

Thesis advisor: Jason Kingsbury / Recent findings have led to the discovery that the Sc-catalyzed addition of substituted diazoalkanes to aldehydes elegantly affords a net carbon insertion into the C-H bond, delivering the requisite ketone in one simple step with no need for a readjustment in oxidation state. This chemistry is much improved over the century old diazomethane chemistry which requires stoichiometric amounts of a promoter and is limited in both application and scope. The new catalytic method has now been utilized as the key step in the synthesis of the pseduosymmetric precursor to the natural product achyrofuran, which has been named “pre-achyrofuran.” Subsequently, a related project was pursued involving the desymmetrization of bicyclic β-diketones by catalytic carbon insertion with trimethylsilyldiazomethane as the reagent. Preliminary developments in this area are disclosed. / Thesis (BS) — Boston College, 2010. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Chemistry Honors Program. / Discipline: Chemistry.

Soft tissue infection in a diabetic foot with an ulcer is often clinically obvious but the diagnosis of osteomyelitis underlying a diabetic foot ulcer is challenging. It has been calculated that there are over 1 million amputations worldwide for diabetes related complications every year, many preceded by an ulcer complicated by osteomyelitis. <br /> This research encompasses two studies attempting to add to the ways in which osteomyelitis is diagnosed. <br /> The first was examining the role of inflammatory blood markers in recognising and separating ulcers with cutaneous infection from both suspected and proven osteomyelitis. The response of the body to produce these markers when an injury occurs is well known but arguments exist as to the capacity of the individual with diabetes to do so. Despite the recognition and allowance for common confounding factors no trend was found. This study may have been more difficult than originally thought due to the many interactions of the diseased state of diabetes, the drugs used to control it and the many other confounders that would have influenced the inflammatory process and as such the level of the markers. <br /> The second study was comparing a new form of scanning technique (SPECT/CT) to the technique most commonly used as a ‘gold standard’ – MRI. The results of each type of scan were compared to the clinical diagnosis and each other. The SPECT/CT scan appears to show some good results and may be a more suitable scan for individuals who are unable to have a MRI for example due to the need to introduce a renally excreted drug to help make the images clearer but it does mean introducing a small amount of radiation into the individual.