Correlation of Estrogen Receptor Alpha Serum Level with Gene Polymorphism and Its Effect on Women with Unexplained Infertility, Basra, Iraq.

Infertility of unknown etiology is considered a significant medical and health problem. This study focused on the role of the estrogen receptor alpha (ESRα) gene polymorphism, PvuII (rs2234693), and its effect on the amount of ESRα in the blood of women who cannot get pregnant for unknown reasons. A total of 184 females were evaluated, including 102 with unexplained infertility (UI) and 82 age-matched control females (with at least one living child and no history of infertility). Blood samples were collected, genomic DNA was isolated from blood samples, and the genotyping of the ESRα gene was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ESRα expression levels were assessed by the ELISA. The study revealed that the mean serum level of ESRα was significantly higher in the case group than in the control group (P<0.05). Furthermore, the genotypes (TT, TC, and CC) and alleles (T and C) significantly influenced the plasma level of ESRα in the study population. Moreover, the presence of the C allele was considered a risk factor, and the polymorphism had a significant effect on ESRα expression level in women with UI.

Effect of Serum Level of Human Epididymis Protein 4 and Interleukin-6 as Biomarkers in Patients with Adnexal Mass.

Ovarian carcinoma is one of the most common types of neoplasms in women and the fifth leading cause of cancer death among women worldwide. Adnexal masses are classified as simple or complicated and can be benign or malignant. No single biomarker has demonstrated high sensitivity and specificity for detecting early ovarian cancer. Therefore, the current study was designed to investigate the influence of using two biomarkers as a tool for diagnosis in patients with an adnexal mass. This prospective case-control study was carried out on female patients diagnosed by ultrasound and magnetic resonance imaging with adnexal masses and scheduled for surgery and healthy women as a control group (n=50 each). The patients were in the age range of 16-80 years old and had attended the surgical rooms of Basrah hospitals, Basrah, Iraq, from January to July 2021. The levels of serum biomarkers were quantitatively assessed using the enzyme-linked immunosorbent assay. The serum concentration of the human epididymis protein 4 (HE4) biomarker exhibited significant differences between females with adnexal mass and healthy women. There was no significant association between neither the patient's age nor the menopausal state and the serum level of HE4. The serum level of HE4 had a sensitivity of 92% and a specificity of 66% as a serum marker for the presence of adnexal mass with a positive predictive value of 73% and a negative predictive value of 89%. In this study, serum interleukin-6 (IL-6) had a sensitivity of 30% and specificity of 64% in determining patients with adnexal mass pathology. It was found that the level of IL-6 was similar in all patients, compared to that in the control group. The median levels of serum HE4 showed high value in patients in the age groups of 21-40, 41-50, and >50 than in the control group; however, it was not statistically different (P=0.413). Human epididymis protein 4 was the top biomarker representing a higher concentration in adnexal mass; moreover, it demonstrated the highest performance in all samples with Adnexal mass. The results of our study showed that combining more than one marker measurement increased both the sensitivity and specificity of distinguishing patients with adnexal mass pathology.

Intense pulsed light versus cryotherapy in the treatment of hypertrophic scars: A clinical and histopathological study.

BACKGROUND: Different therapeutic modalities have been tried for hypertrophic scar treatment. To our knowledge, intense pulsed light (IPL) has not been previously evaluated in comparison with cryotherapy as a stand-alone treatment for hypertrophic scars. OBJECTIVE: We aimed to evaluate the efficacy of IPL as a monotherapy for hypertrophic scar treatment as compared with cryotherapy both clinically and histopathologically. METHODS: This study included 28 patients with hypertrophic scars. Patients were divided randomly and equally into two groups; group I patients received cryotherapy while group II patients received IPL. All patients received treatments for a total of six sessions or until resolution of the lesion whichever was nearer. The outcome was evaluated clinically and histopathologically. RESULTS: Scar height showed a significant decrease and scar color and pliability showed a significant improvement in group I. No significant changes were detected in group II except in scar pliability. Vancouver scar scale (VSS) mean decreased by -53.7% in group I versus -11.5% decrease in group II. Histopathologically, group I showed a significantly increased epidermal thickness and decreased dermal and collagen bundle thickness, while group II showed insignificant histopathological changes. Group I exhibited a statistically significant clinical and histopathological improvement compared to group II, yet with more complications. CONCLUSION: Cryotherapy is more effective than IPL in the treatment of hypertrophic scars both on clinical and histopathological level yet with more complications.

Malignant lymphoma in Al-Qassim, Saudi Arabia, reclassified according to the WHO classification.

OBJECTIVE: To determine the frequency of various types of malignant lymphoma (ML) in the Al-Qassim region of Kingdom of Saudi Arabia (KSA) according to recently introduced the WHO classification. METHODS: For this retrospective analysis, material was available in 385 out of 519 cases diagnosed as ML from 1988-2007. Morphological assessment was followed by immunohistochemistry using a panel of antibodies. The study was conducted at Prince Faisal Oncology Centre (PFOC) of King Fahad Specialist Hospital (KFSH), Buraidah, Al-Qassim, KSA. RESULTS: Out of 385 cases reviewed, 251 (65.2%) had non-Hodgkin lymphoma (NHL) and 117 (30.4%) had Hodgkin lymphoma (HL). Male preponderance (male to female ratio 1.6:1) and a wide age range was observed (6 months to 103 years). B cell neoplasms were the most common NHL seen (81.6%) and diffuse large B cell lymphoma (DLBCL) was the most frequent type of NHL encountered (50.1%). Indolent lymphomas like follicular lymphoma (FL) and small lymphocytic lymphoma (SLL) were rather uncommon (13.2%). T cell lymphoma comprised 18.3% of the NHL. The most common type of HL was nodular sclerosis classical Hodgkin lymphoma (NSCHL) (68.3%). CONCLUSION: In Al-Qassim region of KSA, NHL is the most common ML seen and DLBCL the most common type. Unlike other parts of KSA and Middle East, NSCHL is the most common type of HL encountered.

Infection-associated encephalopathies: their investigation, diagnosis, and treatment.

Reduced level of consciousness is a common clinical finding in acutely sick patients. In the majority of cases a cause for the encephalopathy is readily identifiable,whilst in a minority the aetiology is more difficult to ascertain. Frequently the onset of encephalopathy is associated with, or follows, infection. The mechanisms through which infection leads to encephalopathy are diverse. They range from direct microbial invasion of the brain or its supporting structures, to remote, infection-triggered mechanisms such as acute disseminated encephalomyelitis. Most common however, is the encephalopathy caused through a remote effect of systemic sepsis-septic encephalopathy. This article discusses the clinical presentation and underlying pathogeneses of the acute encephalopathies associated with infection, aiming to aid both their recognition and treatment.

Alternative drugs against Trichomonas vaginalis.

To investigate the effect of drugs other than metronidazole, 3 non-pregnant women infected with Trichomonas vaginalis were treated with doxycycline, 2 x 200 mg/day for 1 week. Another 3 women were treated with praziquantel, single dose, 40 mg/kg body weight. No therapeutic effect was detected for either drug. In vitro, oxytetracycline led to death of T. vaginalis at a concentration of 15 mg in 0.5 mL medium. Extract of Myrtus communis caused death of T. vaginalis at pH 4.65, but failed to do so at pH 6.00. Extract of Eucalyptus comaldensis (50 mg in 0.1 mL medium) at pH 5.35 caused death of T. vaginalis after 24 hours.

Alternative drugs against Trichomonas vaginalis

To investigate the effect of drugs other than metronidazole, 3 non- pregnant women infected with Trichomonas vaginalis were treated with doxycycline, 2x200 mg/ day for 1 week. Another 3 women were treated with praziquantel, single dose, 40 mg/ kg body weight. No therapeutic effect was detected for either drug. In vitro, oxytetracycline led to death of T. vaginalis at a concentration of 15 mg in 0.5 mL medium. Extract of Myrtus communis caused death of T. vaginalis at pH 4.65, but failed to do so at pH 6.00. Extract of Eucalyptus comaldensis [50 mg in 0.1 mL medium] at pH 5.35 caused death of T. vaginalis after 24 hours

A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis.

OBJECTIVE: Identifying and effectively treating erectile dysfunction (ED) can result in an improvement of the quality of life (QoL) in men with multiple sclerosis (MS). METHODS: This randomised, double blind (DB), placebo controlled, flexible dose study with an open label extension (OLE) assessed efficacy, QoL, and safety of sildenafil citrate in men with MS and ED. Overall, 217 men received sildenafil (25-100 mg; n = 104) or placebo (n = 113) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire that includes questions on achieving (Q3) and maintaining (Q4) an erection as well as a global efficacy question (GEQ). QoL was also assessed. RESULTS: After 12 weeks, patients receiving sildenafil had higher mean scores for IIEF Q3 and Q4 compared with those receiving placebo (p<0.0001), and 89% (92/103) reported improved erections compared with 24% (27/112) of patients receiving placebo (p<0.0001). At the end of the OLE phase, 95% of men reported improved erections. Patients receiving placebo during the DB phase showed a nearly fourfold increase in improved erections (97% v 26%). Men receiving sildenafil also showed improvements in five of the eight general QoL questions compared with men receiving placebo (p<0.05). The total mean score for the QoL questionnaire improved by 43% for the sildenafil group versus 13% for the placebo group (p<0.0001). Treatment related AEs were predominantly mild in nature, and no patient discontinued due to an AE. CONCLUSION: Sildenafil treatment for ED in men with MS was effective and well tolerated, and resulted in significant improvements in both general and disease specific QoL variables.

Factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections.

BACKGROUND: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinal fluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited. OBJECTIVE: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results. METHODS: CSF from patients with was tested for human herpesviruses types 1-6, JC virus, enteroviruses, and Toxoplasma gondii. The likelihood of central nervous system (CNS) infection was classified as likely, possible, or unlikely. PCR findings in these categories were compared using single variable and logistic regression analysis. RESULTS: Of 787 samples tested, 97 (12%) were PCR positive for one or more viruses. Of episodes likely to be CNS viral infections, 30% were PCR positive compared to 5% categorised as unlikely. The most frequent positive findings were Epstein Barr virus (EBV), enteroviruses, and herpes simplex virus (HSV). Enteroviruses and HSV were found predominantly in the likely CNS viral infection group, whereas EBV was found mainly in the unlikely group. Positive PCR results were more likely when there were 3-14 days between symptom onset and lumbar puncture, and when CSF white cell count was abnormal, although a normal CSF did not exclude a viral infection. CONCLUSIONS: The diagnostic yield of PCR can be maximised by using sensitive assays to detect a range of pathogens in appropriately timed CSF samples. PCR results, in particular EBV, should be interpreted cautiously when symptoms cannot readily be attributed to the virus detected.

Evaluation of neuromuscular symptoms in UK Gulf War veterans: a controlled study.

OBJECTIVES: To determine whether Gulf War veterans with neuromuscular symptoms that included weakness and fatigue had either 1) objective correlates for muscle weakness or fatigue; or 2) any etiologic explanation for such symptoms; and if so, 3) whether such objective measures or etiologic mechanisms were specific to Gulf War service. METHODS: Forty-nine ill Gulf War veterans with more than four neuromuscular symptoms (Gulf-ill) were compared with 26 Gulf-well veterans, 13 symptomatic Bosnian veterans (Bosnia-ill), and 22 symptomatic troops who were not deployed to the Gulf (Era-ill). Quantitative myometry was used to objectively measure weakness and fatigue. Subjects had an ischemic forearm exercise test, a subanaerobic bicycle exercise test, and a muscle biopsy. RESULTS: Quantitative strength and fatigue measures did not correlate with self-perception of weakness or fatigue for any of our groups. No specific muscle biopsy abnormalities were found. There was no defect of adenylate deaminase or glycogenolysis found. Gulf-ill subjects did find the subanaerobic bicycle exercise more effortful and generated significantly higher plasma lactate concentrations compared with Gulf-well subjects. CONCLUSION: Because complaints of weakness and fatigue in unwell servicemen do not correlate with actual weakness or fatigue, explanations for these symptoms must lie outside of the neuromuscular system. Increased lactate production during subanaerobic bicycle exercise reflects mitochondrial inefficiency, but it is unclear whether this reflects mitochondrial damage sustained during Gulf War service or inactivity secondary to ill health.

Multiple sclerosis: Neurofilament light chain antibodies are correlated to cerebral atrophy.

OBJECTIVE: To evaluate markers of axonal damage in CSF and serum of patients with different subtypes of MS in relation to measures of disease progression on MRI. METHODS: In 51 patients with MS (21 relapsing-remitting, 20 secondary progressive, 10 primary progressive), levels of heavy and light neurofilaments (NfH and NfL) and antibodies to neurofilaments (anti-NfL and -NfH) as well as the total immunoglobulin G (IgG) were analyzed. MRI analysis included T2 hyperintense, T1 hypointense, and gadolinium enhancing lesions and markers of cerebral atrophy (ventricular and parenchymal fractions). RESULTS: For the total group, correlations were found between the anti-NfL index and the parenchymal fraction (PF) (r = -0.51, p < 0.001), T2 lesion load (r = 0.41, p < 0.05), ventricular fraction (r = 0.37, p < 0.05), and T1 lesion load (r = 0.37, p < 0.05). For the anti-NfH index, a correlation was found with the PF (r = -0.39, p < 0.05). No correlations were found between the IgG index and MRI measures. CONCLUSIONS: Intrathecal production of anti-NfL antibodies may serve as a marker of tissue damage, particularly axonal loss, in MS.

Expression ratios of the Bcl-2 family proteins and disease activity in multiple sclerosis.

There is emerging evidence that failure of apoptosis (programmed cell death) of potentially pathogenic T lymphocytes may be involved in the pathogenesis of multiple sclerosis (MS). The commitment of T lymphocytes to die is partly regulated by the Bcl-2 family proteins, which act as a checkpoint upstream of mitochondrial dysfunction. These proteins include the death antagonists Bcl-2 and Bcl-X(L), and death agonists Bax and Bad. Recent studies suggest that altered expression of Bcl-2 family proteins in T lymphocytes is involved in promoting cellular resistance to apoptosis in patients with MS. However, the relationship between these alterations in Bcl-2 proteins expression and clinical disease activity has not yet been evaluated. In this study, we analyzed the expression ratios of pro- to anti-apoptosis Bcl-2 family proteins in patients with clinically active MS and compared results to corresponding ratios in patients with stable MS and relevant control groups. We observed a significant reduction in the expression ratios of pro- to anti-apoptosis Bcl-2 members in peripheral lymphocytes from patients with active MS when compared to corresponding ratios in patients with stable MS or other controls. This imbalance in the expression ratios of pro- and anti-apoptosis proteins was functionally active in reducing cellular susceptibility to apoptosis in active MS. It also correlated with clinical features of disease activity, such as the number of gadolinium-enhancing MRI lesions and clinical relapses. Our findings indicate that dysregulated expression of Bcl-2 family proteins in peripheral lymphocytes is a feature of clinically active multiple sclerosis.

Hypocretin (orexin) deficiency in narcolepsy and primary hypersomnia.

The discovery that hypocretins are involved in narcolepsy, a disorder associated with excessive daytime sleepiness, cataplexy, and unusually rapid transitions to rapid eye movement sleep, opens a new field of investigation in the area of disorders of sleep and activation. Hypocretin-1 (hcrt-1) and hypocretin-2 (hcrt-2) (also called orexin-A and orexin-B) are newly discovered neuropeptides processed from a common precursor. Hypocretin containing cells are located exclusively in the lateral hypothalamus, with widespread projections within the central nervous system. The role of the hypocretin system in other disorders causing excessive daytime sleepiness is more uncertain. This study reports the findings of a prospective study measuring cerebrospinal fluid concentrations of hypocretin-1 and hypocretin-2 in HLA DQB1*0602 positive narcolepsy with cataplexy, monosymptomatic narcolepsy, and primary hypersomnia. The results confirmed the previous observations, that hcrt-1 is deficient in narcolepsy and for the first time report very low levels of hcrt-1 in primary hypersomnia. It is also reported for the first time that there is a generalised defect in hcrt-2 transmission in all three of these clinical entities compared with controls.

Expression of CD5 on B lymphocytes correlates with disease activity in patients with multiple sclerosis.

There is growing evidence that implicates B lymphocytes and their products in the pathogenesis of multiple sclerosis (MS). A subpopulation of B lymphocytes expressing the CD5 antigen are involved in several autoimmune disorders through the release of autoantibodies. In this study, we used three-color flow cytometry to examine the expression of CD5 antigen on B lymphocytes from patients with relapsing-remitting MS, and correlated this expression with features of disease activity and circulating levels of autoantibodies against myelin basic protein. CD5 expression on B lymphocytes was significantly higher in patients with active MS when compared to patients with clinically stable MS or those with inflammatory or noninflammatory neurologic disorders. CD5(+) B lymphocytes from patients with active MS correlated significantly with the number of gadolinium-enhancing MRI lesions, and inversely with disease duration. The expression of CD5 on B lymphocytes in MS patients also correlated with circulating levels antibodies against myelin basic protein. Results presented here indicate that clinically active MS is associated with an expanded population of peripheral CD5(+) B lymphocytes.

Neurophysiologic analysis of neuromuscular symptoms in UK Gulf War veterans: a controlled study.

BACKGROUND: UK veterans who were deployed to the Gulf in 1990 to 1991 reported higher prevalence of neuromuscular symptoms. OBJECTIVE: To investigate whether these Gulf War-related symptoms were associated with objective evidence of neuromuscular dysfunction. METHODS: Forty-nine Gulf War veterans with more than four neuromuscular symptoms (Gulf-ill), 26 Gulf-well veterans, 13 symptomatic Bosnian veterans (Bosnia-ill), and 22 symptomatic veterans who were not deployed to the Gulf (Era-ill) underwent detailed neurophysiologic assessment: nerve conduction studies, quantitative sensory and autonomic testing, and concentric needle and single-fiber electromyography (EMG). RESULTS: Nerve conduction studies detected carpal tunnel syndrome in two Gulf-ill, two Gulf-well, one Bosnia-ill, and three Era-ill veterans. Ulnar neuropathy was detected in one Gulf-ill and two Era-ill veterans. However, results of detailed nerve conduction studies of the Gulf-ill veterans were comparable with results observed in the other three groups. Quantitative sensory and autonomic assessments also failed to show any specific abnormalities in the Gulf-ill group. Similarly, quantitative assessment of concentric needle and single-fiber EMG detected no chronic denervation or myopathic changes or any abnormalities of neuromuscular transmission in the Gulf-ill veterans. CONCLUSION: Gulf War-related neuromuscular symptoms are not associated with specific impairments of peripheral nerves, neuromuscular junctions, or skeletal muscles.

The expression of apoptosis-regulatory proteins in B lymphocytes from patients with multiple sclerosis.

The pathogenesis of multiple sclerosis (MS) is thought to involve T- and B-lymphocyte-mediated autoimmunity. However, the mechanisms that regulate lymphocyte activity in MS are poorly understood. In normal circumstances, programmed cell death (apoptosis) contributes to the maintenance of lymphocytes homeostasis and the deletion of autoreactive cells. Cellular commitment to apoptosis is partly regulated by the cell death receptor Fas, and the anti-apoptosis proteins Bcl-2 and FLIP. Although there is emerging evidence that dysregulations of apoptotic pathways play a role in T-cell autoimmunity in MS, the expression of apoptosis-regulatory proteins in B cells from MS patients is largely unknown. In this study, we analyzed the expression profiles of Fas, Bcl-2, and FLIP proteins in peripheral B lymphocytes from patients with relapsing-remitting and progressive MS, and from appropriate controls. We observed a significant up-regulation of Bcl-2 and FLIP proteins in B cells from relapsing-remitting MS when compared to corresponding expression in progressive MS, or in noninflammatory neurologic controls and healthy individuals. This cellular overexpression of Bcl-2 and FLIP proteins was not affected by treatment with interferon-beta, but was also observed in B cells from patients with systemic inflammatory diseases. Our findings suggest that cellular overexpression of the apoptosis-inhibitory proteins in patients with relapsing MS may promote apoptotic resistance of potentially pathogenic, autoreactive B lymphocytes and consequently, may allow for continuing autoimmune tissue destruction.

Upregulated survivin expression in activated T lymphocytes correlates with disease activity in multiple sclerosis.

Programmed cell death (apoptosis) is critical for the normal development and homeostasis of the immune system. There is emerging evidence that failure of apoptosis to eliminate potentially pathogenic, autoreactive T lymphocytes may be involved in the pathogenesis of multiple sclerosis (MS). This failure is related to multiple abnormalities of apoptosis-regulatory molecules that involve survivin, a recently described cell cycle-regulated anti-apoptosis protein. In this study, we investigated the relationship between survivin expression in peripheral T lymphocytes and clinical features of MS. We detected a significant over-expression of survivin in mitogen stimulated T lymphocytes from patients with active MS when compared with corresponding expression in patients with stable MS or those with inflammatory and non-inflammatory neurologic disorders. This over-expression of survivin in patients with active MS correlated with cellular resistance to apoptosis and with features of disease activity, such as disease duration and the number of enhanced lesions on cranial magnetic resonance imaging. There was no correlation between cellular survivin levels and the expression of other apoptosis-inhibitory proteins, such as Bcl-2 and Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP). Our findings indicate that cellular over-expression of the novel anti-apoptosis protein survivin is a feature of clinically active MS.