Clinicopathological Implications of Mismatch Repair Status in Endometrioid Endometrial Cancer in Duhok City.

BACKGROUND: DNA mismatch repair (MMR) is a specialized system that corrects errors in DNA replication, namely, base substitution mismatches and minor insertion-deletion mismatches. The deficient mismatch repair (d-MMR) protein plays a vital role in predicting the prognosis of endometrioid carcinoma. The study aimed to determine the prevalence of MMR errors in endometrial cancer (EC) and their correlation with clinicopathological features. METHODS: We examined the immunohistochemistry presence of four MMR proteins in 50 samples of EC tissues that were preserved in formalin and embedded in paraffin. The proteins identified were MutL homolog 1 (MLH1), post-meiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6). The study examined several clinicopathological characteristics and conducted MMR phenotyping. RESULTS: The findings revealed that among the 50 cases of EC, 40% of patients had grade I disease and 78% had stage I malignancy. Furthermore, among the 50 individuals evaluated, 56% exhibited competence in MMR, whereas 44% displayed loss in nuclear expression of MMR. The rate of MLH1 and PMS2 protein loss was recorded as the greatest, at 18%, while the loss of MSH2 and MSH6 was documented at 6%. Within the same range, the majority of patients with d-MMR were above the age of 50 years. CONCLUSION: The majority of the recruited EC patients in this study showed advanced age and a high percentage of d-MMR status.

The State of Cardiac Rehabilitation in Saudi Arabia: Barriers, Facilitators, and Policy Implications.

Cardiovascular disease (CVD) is a critical public health issue in Saudi Arabia, where it is the leading cause of death. The economic burden of CVD in the country is expected to triple by 2035, reaching $9.8 billion. This paper provides an overview of CVD in Saudi Arabia and its risk factors, impact on healthcare, and effects on patients' quality of life. The review emphasizes the potential of cardiac rehabilitation (CR) programs in addressing the CVD epidemic. CR programs have been shown to reduce morbidity, mortality, and hospital readmissions while improving patients' cardiovascular health and overall well-being. However, these programs are underutilized and inaccessible in Saudi Arabia. The paper highlights the urgent need for CR programs in the country and suggests key strategies for implementation. These include increasing patient referrals, tailoring programs to individual needs, enhancing patient education, and making CR accessible through home-based options. Fostering multidisciplinary collaboration and developing tailored guidelines for Arab countries can further enhance the impact of CR programs. In conclusion, this review underscores the vital importance of comprehensive CR programs in Saudi Arabia to combat the rising CVD burden, improve patient quality of life, and align with the goals of the Saudi 2030 Vision for a healthier society.

The TGF-beta-pseudoreceptor BAMBI is strongly expressed in COPD lungs and regulated by nontypeable Haemophilus influenzae.

BACKGROUND: Nontypeable Haemophilus influenzae (NTHI) may play a role as an infectious trigger in the pathogenesis of chronic obstructive pulmonary disease (COPD). Few data are available regarding the influence of acute and persistent infection on tissue remodelling and repair factors such as transforming growth factor (TGF)-beta. METHODS: NTHI infection in lung tissues obtained from COPD patients and controls was studied in vivo and using an in vitro model. Infection experiments were performed with two different clinical isolates. Detection of NTHI was done using in situ hybridization (ISH) in unstimulated and in in vitro infected lung tissue. For characterization of TGF-beta signaling molecules a transcriptome array was performed. Expression of the TGF-pseudoreceptor BMP and Activin Membrane-bound Inhibitor (BAMBI) was analyzed using immunohistochemistry (IHC), ISH and PCR. CXC chemokine ligand (CXCL)-8, tumor necrosis factor (TNF)-alpha and TGF-beta expression were evaluated in lung tissue and cell culture using ELISA. RESULTS: In 38% of COPD patients infection with NTHI was detected in vivo in contrast to 0% of controls (p < 0.05). Transcriptome arrays showed no significant changes of TGF-beta receptors 1 and 2 and Smad-3 expression, whereas a strong expression of BAMBI with upregulation after in vitro infection of COPD lung tissue was demonstrated. BAMBI was expressed ubiquitously on alveolar macrophages (AM) and to a lesser degree on alveolar epithelial cells (AEC). Measurement of cytokine concentrations in lung tissue supernatants revealed a decreased expression of TGF-beta (p < 0.05) in combination with a strong proinflammatory response (p < 0.01). CONCLUSIONS: We show for the first time the expression of the TGF pseudoreceptor BAMBI in the human lung, which is upregulated in response to NTHI infection in COPD lung tissue in vivo and in vitro. The combination of NTHI-mediated induction of proinflammatory cytokines and inhibition of TGF-beta expression may influence inflammation induced tissue remodeling.

Noncirrhotic hyperammonemia: A factor behind dementia to alter mental status.

Healthcare givers were recommended to check serum ammonia level for elderly patients with acute-on-chronic alteration of mental status. Early initiation of antihyperammonemia therapy may benefit improvement of alteration of mental status. Baseline mental status becomes necessary for diagnose the acute alteration of mental status and monitor the therapeutic process.

Factors contributing to medicine-related problems in adult patients with diabetes and/or cardiovascular diseases in Saudi Arabia: a qualitative study.

OBJECTIVES: To investigate the factors contributing to medicine-related problems (MRPs) among patients with cardiovascular diseases (CVDs) and/or diabetes in Saudi Arabia. DESIGN: Qualitative semistructured interviews were conducted. Interviews were audio recorded then transcribed into Microsoft Word. The transcribed interviews were then imported into the qualitative analysis software NVivo where thematic analysis was applied. Thematic synthesis was achieved by coding and developing subthemes/themes from the findings of the interviews. SETTING: Five healthcare centres in Najran, Saudi Arabia. PARTICIPANTS: 25 adult patients with diabetes and/or CVDs. RESULTS: The study cohort included 16 men and 9 women with a median age of 61.8 years (40-85 years). Diabetes was the main condition encountered among 23 patients and CVDs were reported among 18 patients. Perceived factors leading to MRPs were of four types and related to: patient-, healthcare system-, clinical (condition-) and medicine-related factors. Patient-related factors were related to living situation, religious practices, diet/exercise and patients' behaviour towards the condition and medicines. Healthcare system-related factors comprised sources and availability of medicines, ease of access to healthcare system and patient satisfaction with healthcare providers. Clinical (condition-) related factors associated with both the knowledge and control over condition, and effects of the condition among medicines intake. Medicine-related factors included lack of knowledge about medicines and medicine use. CONCLUSIONS: The results of this study uncovered many factors associated with MRPs among patients with CVDs and diabetes in Saudi Arabia, especially in reference to lifestyle and medicine use. Improving communication with healthcare professional alongside the introduction of national clinical guidance would mitigate the unwanted health complications related to medicine use.

Hyperbaric oxygen as an adjunctive therapy for bilateral compartment syndrome, rhabdomyolysis and acute renal failure after heroin intake.

Heroin abuse causes various medical and surgical complications. We report a case of heroin-induced severe bilateral compartment syndrome complicated by rhabdomyolysis, acute renal failure and extremely elevated creatinine kinase. A 30-year-old male heroin addict presented to the emergency department of Mount Vernon Hospital, Mount Vernon, New York complaining of severe pain and burning sensation in both legs and feet 1 day after abusing intravenous heroin. He had severe swelling and tenderness of both legs and feet. Laboratory data revealed tremendous elevation of creatine kinase (236,000 IU/L) consistent with rhabdomyolysis. Acute renal failure developed over subsequent days. Treatment consisted of fasciotomy, hyperbaric oxygen therapy (HBO2) and supportive therapy. The condition gradually improved over 4 weeks and the patient did not require dialysis or amputation.

Influences of hyperbaric oxygen on blood pressure, heart rate and blood glucose levels in patients with diabetes mellitus and hypertension.

BACKGROUND: We investigated the influences of hyperbaric oxygen (HBO(2)) on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and blood glucose level (BGL). METHODS: Forty one patients with hypertension (HTN), diabetes mellitus (DM), HTN and DM and/or no HTN or DM underwent HBO(2) sessions (15-40 sessions for each patient). SBP, DBP, HR and BGL (for diabetics) were recorded before and after each session. RESULTS: HBO(2) caused significant elevation in SBP (11%) and DBP (12%) and a decrease in HR (18%) (p <0.001). Patients with DM and HTN showed higher elevation in SBP and DBP. HBO(2) lowered BGL by 23% (p <0.001). When basal BGL was in the range of 120-170 mg/dl, it dropped to <100 mg/dl in 31/60 treatment sessions (52%). When basal BGL was <120 mg/dl it dropped to <70 mg/dl in 8/34 sessions. There was a possibility of lowered BGL when basal BGL was <170 mg/dl and a marked reduction in BGL occurred when basal BGL was <120 mg/dl. HBO(2) caused a marked elevation in SBP and DBP when basal SBP was >140 mmHg. Critical elevation was obtained when SBP was >160 mmHg. The use of beta blockers caused significant elevation of blood pressure while reducing HR. CONCLUSIONS: HBO(2) causes elevation of blood pressure and lowering of HR and BGL, which were augmented in the presence of HTN, DM, or beta blocker. The use of beta blockers for the management of HTN should be avoided during HBO(2) therapy.

Postsurgical psychosis: case report and review of literature.

A wide range of behavioral symptoms may occur following surgery, including depression, hallucinations, true psychosis, mania, and impulsivity. Psychoses, including those that occur postoperatively, are among the most frequent indications for hospitalization in the United States and are associated with a substantially increased rate of morbidity. The exact cause of postoperative psychosis has not been identified. A 59-year-old woman who developed acute psychosis after cholecystectomy is described here. The patient was brought to Mount Vernon Hospital in New York because she exhibited acute disruptive behavior following endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy performed on 2 consecutive days. The patient was psychotic and was unable to be managed; she was disorganized, confused, and perplexed. Findings of computed tomography of the head, electroencephalography, and chemical and hematologic tests were normal. The patient was treated with lorazepam 1 mg every 6 h, olanzapine 5 mg at bedtime, and clonazepam 1 mg at bedtime. She experienced a mixture of auditory and visual hallucinations with a paranoid perspective and was then treated with haloperidol 5 mg, diphenhydramine chloride 25 mg, and divalproex sodium 500 mg. After 1 wk, the patient was described as acutely psychotic; antipsychotic medication dosages were readjusted and the patient's condition stabilized. The association between surgical procedures and psychosis is thoroughly reviewed here. Awareness, ability to diagnose, and an understanding of the cause of psychotic symptoms that emerge following surgery must be established if physicians are to provide better care and more effective treatment.

Effect of Diode Laser on Healing of Tooth Extraction Socket: An Experimental Study in Rabbits.

OBJECTIVES: To evaluate the effect of low-level laser therapy on healing of extracted tooth socket of healthy rabbits. DESIGN: The sample of this study was 20 male rabbits of 2-2.5 kg weight with age range of 8-12 months. Right and left lower first premolar teeth were extracted. The extraction sockets of lower right first premolar were irradiated with 0.9 W gallium-aluminum-arsenide (GaAlAs) diode laser for 5 min, immediately after extraction and then every 72 h for the next 12 days. The extraction socket of left side were not exposed to laser and served as a control. The animals were sacrificed after 7, 14, 30 and 45 days and the experimental and control sockets were removed from the harvested mandibles and prepared for haematoxylin and eosin staining and Masson's stain. The prepared slides were examined under light microscope for histological and histomorphometric examination. RESULTS: The histological examination showed that diode laser-treated sockets demonstrated early formed new bone with faster maturation of primary bone to secondary bone as compared to non-treated control sockets. Histomorphometric analysis revealed a statistically significant increase in the density and volume of trabecular bone in laser-treated sockets than control sockets. CONCLUSION: Diode laser application to tooth extraction socket has a positive effect on bone formation.

Hyperbaric oxygen in the treatment of patients with cerebral stroke, brain trauma, and neurologic disease.

Hyperbaric oxygen (HBO) therapy has been used to treat patients with numerous disorders, including stroke. This treatment has been shown to decrease cerebral edema, normalize water content in the brain, decrease the severity of brain infarction, and maintain blood-brain barrier integrity. In addition, HBO therapy attenuates motor deficits, decreases the risks of sequelae, and prevents recurrent cerebral circulatory disorders, thereby leading to improved outcomes and survival. Hyperbaric oxygen also accelerates the regression of atherosclerotic lesions, promotes antioxidant defenses, and suppresses the proliferation of macrophages and foam cells in atherosclerotic lesions. Although no medical treatment is available for patients with cerebral palsy, in some studies, HBO therapy has improved the function of damaged cells, attenuated the effects of hypoxia on the neonatal brain, enhanced gross motor function and fine motor control, and alleviated spasticity. In the treatment of patients with migraine, HBO therapy has been shown to reduce intracranial pressure significantly and abort acute attacks of migraine, reduce migraine headache pain, and prevent cluster headache. In studies that investigated the effects of HBO therapy on the damaged brain, the treatment was found to inhibit neuronal death, arrest the progression of radiation-induced neurologic necrosis, improve blood flow in regions affected by chronic neurologic disease as well as aerobic metabolism in brain injury, and accelerate the resolution of clinical symptoms. Hyperbaric oxygen has also been reported to accelerate neurologic recovery after spinal cord injury by ameliorating mitochondrial dysfunction in the motor cortex and spinal cord, arresting the spread of hemorrhage, reversing hypoxia, and reducing edema. HBO has enhanced wound healing in patients with chronic osteomyelitis. The results of HBO therapy in the treatment of patients with stroke, atherosclerosis, cerebral palsy, intracranial pressure, headache, and brain and spinal cord injury are promising and warrant further investigation.

Skin squamous cell carcinoma presenting as cellulitis.

In general, skin squamous cell carcinoma (SCC) presents as papules or plaques with erythematous or pigmented appearance that may ulcerate the skin. Cellulitis caused by metastatic deposit from a known primary skin SCC has been reported once.1 We describe a patient who presented with cellulitis on the face that did not respond well to full course of antibiotics treatment, and turned out to be a newly diagnosed SCC after biopsy. Other differential diagnoses, such as malignancy, should be suspected in all unusual presentations and biopsy should be taken if patients do not show an optimal and desired improvement after receiving a full-course of antibiotic therapy for cellulitis.

Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung.

Since the existence of pHp was demonstrated, it has been shown that this molecule and its receptor CD163 are regulated by different stimuli. Furthermore, a comparably fast secretion of pHp was described as well as the immuno-stimulatory effects. The intention of this study was to elucidate the role of pHp in the human lungs further. Here we show, by means of confocal microscopy and immune-electron-microscopy, a clear co-localization of pHp with surfactant protein-B in lamellar bodies of alveolar epithelial cells type II. These results are underlined by immunohistochemical stainings in differently fixed human lung tissues, which show pHp in vesicular and released form. The images of the released form resemble the intended position of surfactant in the human alveolus. pHp is secreted by Alveolar epithelial cells type II as previously shown. Moreover, pHp is co-localized with Surfactant protein-B. We conclude that the presented data shows that pHp is a native part of the surfactant system in the human lung. VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/2563584738239912.

HOPE-BAL: improved molecular diagnostics by application of a novel technique for fixation and paraffin embedding.

The bronchoalveolar lavage (BAL) and its cells have been widely used as a support for clinical diagnosis and as a versatile tool for research questions since many years. Because there are no sufficient possibilities of long-term storage, the authors explore in this study the utility of a new fixative for fixation and paraffin embedding of human lavage cells with the possibility of implementing standard molecular biology techniques. HOPE-fixed, paraffin-embedded BAL cells of patients with different lung diseases (asthma, chronic obstructive pulmonary diseases, tuberculosis, sarcoidosis, emphysema, and fibrosis) were subjected to immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, and transcription microarray analysis. Furthermore, two-dimensional gel electrophoresis was conducted to evaluate the range of possible applications for research, diagnostics, and further implementing in biobanks. The authors show, by targeting some exemplary molecules, the power of screening and validating HOPE-BAL for new biomarkers. The transforming growth factor ß signaling pathway may play a central role in immunomodulation upon infection as well as asthma. Furthermore, haptoglobin was overexpressed in asthma and sarcoidosis. Because of the excellent preservation of nucleic acids, protein, and morphologic structures, HOPE-BAL is a step forward into enhanced molecular diagnostics and biobanking in pulmonary medicine.

Proteomics out of the archive: Two-dimensional electrophoresis and mass spectrometry using HOPE-fixed, paraffin-embedded tissues.

Proteome analyses provide diagnostic information which can be essential for therapeutic predictions. The application of such techniques for analyzing paraffin-embedded tissue samples is widely hampered by the use of formalin fixation requiring antigen retrieval procedures in molecular pathology. In prior studies, the HEPES-glutamic acid buffer-mediated organic solvent protection effect (HOPE) technique of tissue fixation has been shown to provide a broad array of biochemical investigations with excellent preservation of morphological structures, DNA, RNA, and proteins, thus supporting the multimethod analysis of archived specimens. Here we show that HOPE fixation is also useful in proteomic investigations by allowing two-dimensional electrophoresis (2DE) and mass spectrometry, using lung cancer tissues. Two-dimensional gels of two-protein extraction protocols derived from HOPE-fixed material displayed characteristic spot patterns with high reproducibility. For comparison, 2DE analysis of ethanol-fixed, formalin-fixed, and frozen samples from the same tissues was performed. Western blotting confirmed immunoreactivity of 2DE-separated proteins from HOPE-fixed tissue samples. Additionally, distinct spots were excised from HOPE-derived 2D gels and successfully subjected to peptide mass fingerprinting. In conclusion, paraffin archives containing HOPE-fixed tissues are applicable to a wide spectrum of molecular investigations including common biochemical methods for proteome analyses and therefore represent a unique source for molecular investigations in the rapidly growing field of molecular pathology. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

On the significance of Surfactant Protein-A within the human lungs.

Surfactant Protein-A (SP-A) is the most prominent among four proteins in the pulmonary surfactant-system. SP-A is expressed by alveolar epithelial cells type II as well as by a portion of non small cell lung carcinomas (NSCLC).The expression of SP-A is complexly regulated on the transcriptional and the chromosomal level. SP-A is a major player in the pulmonary cytokine-network and moreover has been described to act in the pulmonary host defense.By the use of cell culture or animal models the functional properties have been repeatedly shown in many aspects, often bearing surprising properties which strongly indicate the physiological importance of SP-A. To date SP-A is recognized as a molecule essential for pulmonary development, structure and function. An upcoming number of reports deals with the role of SP-A for pulmonary pathology. This article gives an overview about the state of knowledge on SP-A focused in applications for human pulmonary disorders and points out the importance for pathology-orientated research approaches using immunohistochemistry or in situ hybridization as promising methods to further elucidate the role of this molecule in adult lung diseases.

Expression of the acute phase protein haptoglobin in human lung cancer and tumor-free lung tissues.

Besides its main function, i.e., the binding of free hemoglobin and prevention of oxidative stress, the acute phase protein haptoglobin acts as a potent immunoreactive modulator. As part of an investigation that aimed at illuminating the role of acute phase proteins in the local defense of the lungs, this study is the first to describe the expression and synthesis of haptoglobin in human lung tissues and lung tumors. Prompted by the results obtained from a transcription array study, we analyzed 115 lung (cancer) specimens using immunohistochemistry. Thirty-seven specimens were subjected to mRNA-in situ hybridization. 40.4% of the adenocarcinomas showed distinct granular and perinuclear staining of the tumor cells. By contrast, only 4.8% of the squamous cell carcinomas showed haptoglobin within tumor cells, but 19% displayed haptoglobin expressing alveolar epithelial cells type II surrounding the tumor. One small cell lung cancer displayed haptoglobin expression. In tumor-free lungs, we located haptoglobin in alveolar macrophages, alveolar epithelial cells type II, and bronchiolar cells. In situ hybridization verified the results of immunohistochemistry. The results were further verified by RT-PCR and Western blot compared to liver tissues, which both showed comparable amounts of haptoglobin mRNA and protein in NSCLC and in liver, while tumor-free lung tissues showed lower expression. Due to the known immunomodulatory effects of haptoglobin, its broad expression and synthesis within human lung tissues strongly suggests a function as a fundamental pulmonary local defense element.

The human placenta releases substances that drive lung cancer into apoptosis.

BACKGROUND: As there is no optimal treatment of non small cell lung cancer due to its resistance to common chemotherapeutics, we investigated the effect of human placenta-conditioned medium on tumor tissue. The human placenta constitutes a mixture of maternal and fetal origin and displays a variety of immunomodulatory aspects. METHODS: Freshly resected non small cell lung cancer tissues were incubated with placenta-conditioned medium in a short-term tissue culture model and A549 cells were challenged, respectively. Term placenta was used for producing conditioned medium and HOPE-fixed stimulated tumor tissue was analyzed for expression of caspase-3 and Ki67 via immunohistochemistry. The effects of conditioned medium on squamous cell carcinoma were further compared to physiological concentrations of Carboplat/Gemzar. RESULTS: Conditioned medium caused in 2 of 3 cases elevated expression of caspase-3 and reduced expression of Ki67 in 3 out of 3 cases, while the chemotherapeutic agents caused no comparable expression of caspase-3 or reduction of Ki67. In cell culture up to 50% of karyopyknosis was investigated and even sterile-filtrated medium caused widespread reduction of Ki67 on protein level. CONCLUSION: Human placenta releases substances that mediate apoptosis and reduce proliferation in tumor tissue and cell culture. As even sterile-filtrated medium caused the mentioned effects we hypothesize one or more soluble mediators. The detailed way of promoting apoptosis and nature of these mediators need to be elucidated in further studies.