Dr. Ramesh Gurunathan
Genaral Surgery, Sunway Medical Center, Malaysia.

ISBN 978-93-90888-50-4 (Print)
ISBN 978-93-90888-55-9 (eBook)
DOI: 10.9734/bpi/hmmr/v8

This book covers key areas of medicine and medical research. The contributions by the authors include chronic heart failure, neprilysin inhibitor, valsartan, cardiac resynchronization therapy, Parkinson's disease, neurological disorders, COVID-19, emergency surgery, neonates, method validation, Immunoblot SDS-PAGE, densitometry, animal models, vascularized composite allo transplantation, immunosuppressive regimens, air pollution, allergic rhinitis, diabetes mellitus pre-diabetes, cardiovascular risk, diabetic retinopathy, visual disability, high-density lipoprotein, insulin resistance, oxidative stress, intracranial embolism, therapeutic embolization, granulomatous dermatitis, systemic disease, granuloma annulare, Sjogren syndrome, neurocysticercosis, central nervous system, epilepsy, diet induced obese mouse, myocytes, enucleation, marsupialization, inflammatory lesions, radicular cysts, gabapentinoids, pregabalin, gabapentin, chronic pain conditions, oncology, cancer treatment, insulin potentiation targeted low dose, low-dose chemotherapy, malignant neoplastic diseases. This book contains various materials suitable for students, researchers and academicians in the field of medicine and medical research.


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A Comparative Research on Conservative and Device Treatments in Chronic Heart Failure

Eyubova Ulviyya Aladdin

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 1-11

Being a very common condition among the whole population of the world, often leading a life-threatening illness and having high risk and mortality rate, chronic heart failure (CHF) is also a major public health problem for the world [1]. Our goal is to investigate what has been achieved in the treatment of CHF patients with a left ventricular ejection fraction (LVEF) < 40% recent years. In recent years, it is revealed that BNP has been crucial in the pathogenesis of heart disease. Due to this reason, we tried to investigate the results of the complex medical treatment method performed with the combination of sacubitril / valsartan which is angiotensin receptor neprilysin inhibitor in CHF patients. We also investigated the device treatment methods used in the treatment of these patients, particularly the cardiac resynchronization therapy (CRT).

Finally, we investigated the results of the complex medical treatment method performed with the combination of sacubitril / valsartan which is angiotensin receptor neprilysin inhibitor in comparison with the those of the cardiac resynchronization therapy. Patients treated in this way (with CRT) are forced to stop their labor activity even for a short period of time. Moreover, the CRTs are far more expensive than conservative treatment.

Recent Study on SLP and Parkinson's Disease (PD)

Amany Sakr

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 12-17

Parkinson's Disease (PD)is one of the most common non-curable neurological disorders up till now. It is also a progressive neurodegenerative disease. It is a progressive disorder that affects movement and progresses slowly, beginning with a minor tremor in just one hand. In the early stages of Parkinson's disease, the face may have little or no movement, and the arms may not swing while walking. As the disease progresses, voice may become soft or slurred, and symptoms may worsen.

Background: The current coronavirus disease 19 (COVID-19) pandemic is reshaping health-care delivery and has had a significant effect on surgical patient management. Surgical operations were gradually decreased at the General Surgery Department of Sant' Anna University Hospital in Ferrara, Italy, during the peak of the COVID-19 outbreak in Italy. Just one operating room was available for elective cancer surgery and another for emergency procedures during this period.Furthermore, the number of surgical patient beds had to be reduced in order to make room for the new COVID-19 wards.

Aim: To compare two time spans (March 9 to April 9 2019 and March 9 to April 9 2020), looking for variations in the number and form of emergency surgery operations at a main university hospital in Ferrara, Emilia Romagna, northern Italy.

The analysis of patient results was a secondary goal.

Methods: This retrospective study was carried out at the General Surgery Department of Sant’ Anna University Hospital in Ferrara, Italy. During the peak of the COVID-19 outbreak in Italy and the ensuing complete lockdown, we looked at the number of emergency surgeries conducted and patient outcomes. The number of surgeries performed and their results over the same time in 2019 were then compared. The study examined all adult patients who underwent emergency surgery from March 9 to April 9, 2019 (n = 46) and those who underwent surgery during the first month of the lockdown, from March 9 to April 9, 2020 (n = 27).  Age, gender, American Society of Anesthesiologists classification ratings, and styles of surgery were all factored into the analyses. To summarise the results, descriptive statistics were obtained.

Results: During the first month of the lockdown (March 9 – April 9, 2020), a total of 27 patients underwent emergency surgery at Sant' Anna University Hospital in Ferrara. In comparison to the same timeframe in 2019, this reflects a 41.3 percent decrease in the number of patients who were admitted and underwent emergency surgery. The complication rate during the pandemic period was substantially higher than it was during the analogous period in 2019: 15 out of 27 cases from March 9 to April 9, 2020 (55) vs 17 out of 46 cases from March 9 to April 9, 2019 (36.9). Of the 27 patients who underwent emergency surgery during the pandemic, 10 were screened for COVID-19 using both thorax high resolution computerized tomography and a naso-pharyngeal swab, while 9 only underwent thorax high resolution computerized tomography. Only 1 patient tested positive for SARS-CoV-2 and died following surgery.

Conclusion: During the COVID-19 pandemic, our centre had seen a significant reduction in emergency surgeries, and it's likely that other centres across Italy had similar reductions.

The Validation of Immunoblot Sds-Page as a Qualitative and Quantitative Method for the Determination of Urinary Cystatin C Inneonates

C. Grasselli, A. Barbati, L. Cesarini, R. Pellegrino, G. C. Di Renzo

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 26-39

Introduction: The quantitative determination of urinary Cystatin C (cyst-C) associated with the qualitative analysis of its polymorphisms is an excellent method for early identification of newborns predisposed to renal function impairment. PETIA, PENIA and EIA are the immunometric methods used for the quantitative determination of cyst-C inhuman biologic fluid but they have limitations and do not allow qualitative analysis. The present study is a validation of Immunoblot SDS-PAGE for the qualitative and quantitative analysis of urinary cyst-C.

Methods: Urine was collected from neonates in the nursey at S. Maria della Misericordia Hospital. Urinary cyst-C was investigated by the immunoblot SDS-PAGE and by reading of optical density.

Results: The qualitative analysis showed two different molecular forms: A reactivity at about 70 KDa in all samples and a reactivity at 13 KDa in a limited number of samples. This analysis allows the correlation of the polymorphisms of cyst-C with specific alterations of renal function in newborns. The quantitative analysis is specific, sensitive and accurate.

In fact the coefficient of variation for assay precision was 10% and for assay accuracy was ± 10%, the detection limit was 0.009 ng/ µL and the calibration line has satisfactory linearity (range 0.02-0.3 ng/µL). The stability of urinary cyst-C was acceptable, even without the use of protease inhibitors, as long as the assay was performed on freshly recruited urine or immediately after thawing the samples, which had been stored for up to six months.

Conclusion: Immunoblot SDS-PAGE analysis is a valid method of obtaining a qualitative and quantitative analysis of urinary cyst-C. This method presents unique information about a previously unknown 70 KDa cyst-C form. The assay may offer potential diagnostic information not available with immunometric method.

The development of vascularized composite allotransplantation (VCA) and its clinical need has led to the need for more animal models to study and perform the research required to further this specialty in terms of functional recovery and immunomodulatory improvements. Most of the research currently being done in the VCA is to improve the safety profile of such procedures, in particular with the need to improve immunosuppressive regimens. Much of the animal models are reported in individual series in the literature but there has not been a review as such of these models. Here we present a compilation of the animal models reported in the literature thus far in VCA. A comprehensive review of the literature was performed for any studies which involved the use of animal models in various aspects of VCA research. The models were organized according to the type of VCA transplant, whether they were orthotopic or heterotopic, immunosuppressive regimen each study used and investigation purpose. Twenty-two facial transplant models were reported, 3 abdominal wall transplants, 4 penile transplantations, 21 uterus transplantations, 13 hindlimb transplantations and 4 myocutaneous flap transplantation animal models were reported. Primates, swine, rats, mice, rabbits, sheep and dog animal models in VCA were also reported. The most used immunosuppressive drugs are calcineurin inhibitor such as cyclosporin A and tacrolimus in these VCA animal models. They can significantly suppress lymphocyte function by blocking the phosphatase activity of calcineurin of lymphocytes. They are sometimes used combined with mycophenolate mofetil or steroids or antilymphocyte serum. The review of existing animal models will allow further research to be focused in other areas of VCA where there is a current paucity of literature. The immunosuppressive regimens used in each animal model can also be reviewed to determine which regimen works in which type of animal model which will save time and resources for future research.

Introduction: The work environment is one of the main causes of allergic rhinitis. The majority of vendors in Dakar work in places close to roads that are very frequented by vehicles, exposing them to increased air pollution. The study determined the prevalence of allergic rhinitis and its associated risk factors in these vendors.

Methods: This was a cross-sectional survey based on a structured questionnaire, conducted among vendors in the neighborhoods of HLM, Medina and Petersen in Dakar, Senegal. A total of 200 vendors were interviewed. Symptoms of allergic rhinitis were defined as the simultaneous presence of rhinorrhea, nasal congestion and sneezing in the absence of respiratory infection. A logistic regression analysis was performed to determine the relationship between socio-demographic characteristics, occupational factors, and allergic rhinitis.

Results: Results of the study show a prevalence of 43% of allergic rhinitis among vendors. Multivariate analysis showed that the independent factors associated with allergic rhinitis in these vendors were age [OR: 3.28 (1.02 - 10.51)], working area [OR: 8.31 (2.39 - 28.95)], exposure to multiple sources of pollution [OR: 4.08 (1.43 - 11.63)], and recurrent cold [OR: 4.39 (1.15 - 16.85)].

Conclusion: The prevalence of allergic rhinitis was high among vendors in Dakar. With the rapid and continuous urbanization process, more and more people are exposed to high levels of air pollution.  Our data suggest that exposure to air pollution at the workplace in vendors could lead to allergic rhinitis.

Investigating the Prevalence Rates and Cardiometabolic Determinants of Diabetes Mellitus and Pre-diabetes with Projected Coronary Heart Disease at Bank Site of Brazzaville

Gombet Thierry, Longo-Mbenza Benjamin, Ellenga-Mbolla Bertrand, Ikama M. Stephan, Kimbally-Kaky Gisèle, Nkoua Jean-Louis, Nge Okwe Augustin

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 66-79

Background: Aim: Congolese Bank employees are often inactive without valid information on the burden of dysglycemia and cardiometabolic risk. This study aims to assess the prevalence rates of diabetes mellitus (DM) and pre-diabetes and to identify the environmental, genetic and cardiometabolic risk factors associated with Type 2 diabetes mellitus (T2DM) and pre-diabetes among Congolese bank employees. The very high level of metabolic disorders may be explained by physical inactivity, nutrition transition and epidemiological transition.

Methods: In representative 126 bank employees from Brazzaville, Congo, Central Africa, Abdominal obesity, dyslipidemia and metabolic syndrome (MetS) were defined by IDF for Europe, NCEP-ATPIII and IDF criteria modified for Central Africa. Projected high 10-year total risk of coronary heart disease (CHD) ?20% was calculated using Framingham scores.

Results: Out of the employees, 16% and 21.4% had DM and pre-diabetes, respectively. The rate of T2DM among diabetics was estimated 90%. Aging, high total cholesterol, high LDL-cholesterol, high conicity index and longer urban residence after migration were significantly associated with prediabetes. Physical inactivity, smoking, excessive alcohol intake, abdominal obesity, female gender, low HDL-C, hypertension, CHD, projected high 10-year total CHD risk, age ? 55 years, urban residence, Southern area residence, high socioeconomic status, non married status, MetS/NCEP, MetS/IDF for Europe and MetS/IDF for Africa were significantly associated with T2DM. MetS/IDF for Africa was the only independent determinant of T2DM.

Conclusion: Urgent prevention and intervention programme are needed to curb the alarming increase in DM, T2DM, pre-diabetes.

Associations of High-Density Lipoprotein Cholesterol and Framingham Cardiovascular Risk in African Type 2 Diabetics with Diabetic Retinopathy

Benjamin Longo-Mbenza, Moise Mvitu Muaka, Thierry Gombet, Igor Longo Phemba, Steve Cook, Emmanuel Mve Mengome

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 80-92

Objectives: To assess the associations of high-density lipoprotein cholesterol (HDL-C) and Framingham cardiovascular (CVD) with diabetic retinopathy (DR). DR is the most frequent cause of visual disability (VD) worldwide.

Methods: A cross-sectional study of random sample of 200 T2DM Central Africans. Socio-biographical, laboratory and eye examination main outcome measures were investigated using Tertiles of HDL-C (stratification = lowest <40 mg/dL, normal or intermediate = 40 - 74.9 mg/dL, highest ? 75 mg/dL) and Framingham risk stratification (<10% and ?10%) by logistic regression models.

Results: Out of 200 T2DM patients, 120 (35.5%) had DR and out of DR patients, 116 (n = 96.7%) had VD. There was a significant U- shaped relationship between DR rates and HDL-C stratification. In the normal HDL-C group, elevated 8-hydroxydeoxyguanosine and 10-year Framingham risk > 10% were the significant independent determinants for DR. In the highest HDL-C group, smoking status and 10-year Framingham risk ? 10% were the significantly independent determinants for DR. In 10-year Framingham risk ? 10% group, smoking status, insulin resistance and increasing levels of HDL-C were the significant independent determinants for DR.

Conclusion: DR and VD remain a public health problem in T2DM Central Africans. Some Central Africans with DR and VD appear to have higher HDL-C than T2DM Central Africans without DR and VD. HDL-C in T2DM patients with DR, may be more tightly controlled by genetic factors (black Bantu ethnicity) than the other lipoproteins as reported among Indians, African-Americans, and Japanese individuals. The most preventable environmental risk factors for DR were smoking status, global cardiovascular disease risk, insulin resistance and oxidative stress.

Cerebral Lipiodol Embolism after Interventional Lymphatic Embolization

Piet Waelkens, Sofian Bouneb, Johan Vandommele

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 93-97

Onset of neurological symptoms early after intranodal lymphangiography can occur due to Lipiodol droplet migration through intrapulmonary lymphovenous communication. Lipiodol-based lymphangiography is a diagnostic and therapeutic tool by embolizing lymph leakages. Patients with possible intra-cardiac shunts are at risk. Treatment is supportive.

Granulomatous Dermatitis and Systemic Disease: An Association to Consider

Alberto Corrà, Lavinia Quintarelli, Alice Verdelli, Francesca Portelli, Daniela Massi, Marzia Caproni

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 98-103

Granuloma annulare and interstitial granulomatous dermatitis are granulomatous dermatoses with variable clinical appearances. Granuloma annulare is associated with diabetes mellitus, metabolic syndrome, chronic infections and malignancies, while two Japanese reports described unusual cases of interstitial-type Granuloma annulare in setting of Sjogren syndrome. Interstitial granulomatous dermatitis was associated with rheumatoid arthritis, systemic lupus erythematosus and autoantibodies. We report a case-series of six patients with granuloma annulare or interstitial granulomatous dermatitis, in which half of the patients were diagnosed with Sjogren syndrome, while all of them presented ANA-positivity and the majority reported arthralgia. In many cases, granuloma annulare showed interstitial-type histology, arising challenges in differential diagnosis with interstitial granulomatous dermatitis. The overlap of clinical and histological features of granuloma annulare and interstitial granulomatous dermatitis can be explained considering them as a broad disease spectrum, including also the other forms of reactive granulomatous dermatitis. These conditions should be considered as an indicator of possible systemic disorders or other immunological dyscrasias, for which patients must be screened. Sjogren syndrome may be associated with granuloma annulare also in Caucasians.

Neurocysticercosis: Are the Criteria Diagnostic Enough?

Ildefonso Rodriguez-Leyva, Alejandro Orozco-Narvaez, Adriana Patricia Martínez Mayorga

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 104-116

Neurocysticercosis (NCC) is a common disease produced by helminths (larval form of Taenia Solium) in the Central Nervous System (CNS). It is one of the common causes of epilepsy in the world. Without aggressive treatment, it continues to be associated with high mortality, with intracranial hypertension, and a lack of seizure control. This chapter reviews several cases of patients with secondary epilepsy who meet the diagnostic criteria for NCC and compares 2001 and 2016 diagnostic criteria: one of the cases with a definitive diagnosis, and the rest with a probable diagnosis. This problem is common for residents of regions where cysticercosis is an endemic zone, like in Mexico. Most patients presented clinical courses and image studies highly suggestive of NCC and positive ELISA testing for cysticerci in CSF. We emphasize the importance of ruling out the differential diagnosis, especially in endemic areas, questioning the use of ELISA in the CSF testing for cysticerci antibodies seems to be not enough, and advise caution when interpreting cystic lesions as having a discernible scolex because potential mimics are not infrequent.

Increased Expression of AQP7 in the Skeletal Muscles of Diet Induced Obesity Mice

Yoshihiro Wakayama, Satoshi Hirako, Takahiro Jimi, Seiji Shioda

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 117-127

Aquaporin (AQP) 7 and AQP9 are membrane proteins and are the members of aquaglyceroporin which transports glycerol in addition to water molecule. Glycerol is a direct source of glycerol-3 phosphate for the synthesis of triglyceride which is a main substance of lipid droplet seen in skeletal myofibers. We thought that the expression of AQP7 and AQP9 would be altered in the skeletal myofibers in diet-induced obese (DIO) mice as compared with that of control chaw-fed mice. Both RNA and protein levels of AQP7 and AQP9 were studied in the quadriceps femoris muscles of DIO mice and normal control mice. Real time quantitative RT-PCR analysis showed that mouse AQP7 mRNA levels in skeletal muscles were significantly higher in DIO mice compared with normal control mice (P < 0.01); whereas mouse AQP9 mRNA levels were not different between the two groups (P > 0.05). Histochemically the myofibers of DIO mice contained numerous lipid droplets in oil red O stain samples. Immunohistochemical study of DIO mouse muscles showed enhanced expression of AQP7 at the myofiber surface membranes; while expression of AQP9 appeared to be similar to that of normal control mice. These findings imply that the up-regulated expression of AQP7 in DIO mouse muscles facilitates the secretion of glycerol from myocytes.

Management of Radicular Cyst of Primary Molar

Shilpi Tiwari, B. Nandlal, Sudhakar Reddy

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 128-134

Children's oral cavity can find a variety of inflammatory lesions. Radicular cysts are odontogenic in nature and relatively uncommon in the primary dentition, accounting for just 0.5 to 3.3 % of all radicular cysts in both the primary and permanent dentition. Treatment options for these cystic lesions include: endodontic therapy, extraction of the involved tooth, cyst enucleation or marsupialization. This case report describes surgical management of radicular cyst associated with an infected primary molar and a review of the literature.

Gabapentinoids, pregabalin (LyricaTM) and gabapentin (NeurontinTM) are anticonvulsants that have been approved for chronic pain conditions such as diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, and are also widely prescribed off-label for chronic low back pain. Prescriptions for gabapentinoids have increased rapidly in the last five years, however, the evidence for its efficacy can be conflicting and will be analyzed for each of these chronic pain conditions. The adverse event rates and safety profile will be examined, including case reports of the occurrence of serious adverse events, to ascertain whether gabapentinoids have the potential to cause harm above the benefit of providing effective pain relief. Additional case reports that record extreme withdrawal syndromes In order to weigh the advantages over the risks, it will contribute to the body of evidence and will recognize places where study is lacking. The resulting realistic guidelines for evaluating gabapentinoid treatment for chronic pain will be based on the review of proof of effectiveness, adverse events and withdrawal.

Three Year Study of Insulin Potentiation Therapy in the Treatment of Malignant Neoplastic Diseases

Christo Damyanov, D. M. Gerasimova, L. A. Avramov, I. K. Masley, Ivan Maslev

Highlights on Medicine and Medical Research Vol. 8, 3 May 2021, Page 152-160

Problem Statement: Even after decades of scientific research, the application of chemotherapy in the management of neoplastic disease still presents numerous difficulties. Significant, amongst potential complications are numerous toxicity related side effects and the potential for chemoresistance. Despite the widespread tendency to include a variety of new chemotherapeutics in different combinations, progress in this area has proven slow going and unsatisfactory due to the aforementioned factors.

Approach: Seeking a new approach, we introduced the method of Insulin Potentiation Therapy (IPT) in our practice. The theoretical basis and the gathered experimental data on insulin’s mode of action, as well as its application in practice, show that IPT is a promising method with low toxicity. Moreover, it facilitates a selectively physiological approach to the management of neoplastic disease using chemotherapy.

In this report we present the results of our three-year experience applying Insulin Potentiation Targeted Therapy Low Dose (IPTLD) in the treatment of 196 patients diagnosed with a variety of neoplastic diseases.

Results: Our results showed that patients tolerated IPTLD without difficulties, without serious side effects. Our laboratory tests demonstrated that the dose related toxicity of chemotherapeutics could be largely mitigated when applied in conjunction with insulin, at a fractionated dose in accordance with a dose dense regimen. Upon follow-up, eighty five of 106 patients (80%) with advanced metastatic disease reported a subjectively significant improvement in their quality of life.

Conclusions: Future extended experimental data and clinical trials would contribute to a more complete understanding of the therapeutic potential of IPTLD. The results we achieved, applying IPTLD, and most importantly its lower toxicity, enabled us to apply it as a leading method in the therapy of cancer patients in our practice.