Patterns of thyroid tumors in Northern Saudi Arabia with a specific focus on CK19, CD56, and Galectin-3 tumor markers.

OBJECTIVE: The goal of this study was to look at the patterns of thyroid tumors and how thyroid cancer markers showed up in immunohistochemistry in Northern Saudi Arabia. PATIENTS AND METHODS: This study investigated retrospectively 190 patients who attended with thyroid complaints. About 140 thyroid biopsies were diagnosed in the Department of Pathology at King Salman Hospital, Ha'il, from November 2019 to November 2020. RESULTS: Out of the 190 patients who attended with thyroid complaints, 140/190 (73.7%) were detected with thyroid lesions (58 malignant and 82 benign). Benign lesions included goiter 49/82 (60%), follicular adenoma 17/82 (21%), Hashimoto's thyroiditis 13/82 (16%), and toxic goiter 3/82 (3%). 5/6 (83.3%) of males with benign lesions had goiters. CK19 was positive in 68.5% of the cases; 71.8% were papillary, 66.7% were follicular, and 100% were undifferentiated carcinomas. Out of the 26/54 (48%) CD56-positive cases, 18/39 (46%) were papillary, 7/12 (58.3%) were follicular, and 3/3 (100%) were undifferentiated carcinomas. Out of the 35/54 (64.8%) Galectin-3-positive cases, 69.2% were papillary, 7/12 (58.3%) were follicular, and 3/3 (100%) were undifferentiated carcinomas. CONCLUSIONS: Thyroid cancer is prevalent in northern Saudi Arabia, with the predominant type being papillary thyroid carcinoma. Most patients are female and younger. The combined use of CK19, CD56, and Galectin-3 tumor markers assists in the accurate differential diagnosis of thyroid neoplasms.

Expression of ER, PR, HER2, and Cadherin tumor markers in a series of Saudi patients with BC.

OBJECTIVE: Breast cancer (BC) tumor markers have an important implication in the subsequent BC management and survival determinants. Thus, the present study aimed to formulate the expression of ER, PR, HER2, and E-cadherin tumor markers in a series of Saudi patients with BC. PATIENTS AND METHODS: About 133 BC biopsies were retrieved from the Department of Pathology at King Salman Hospital, Hai'l, Northern Saudi Arabia, from November 2019 to November 2020. Out of the 133 biopsies, 50 (37.6%) were diagnosed with BC, including 46 ductal carcinoma, 2 lobular carcinomas, and 2 papillary carcinomas. RESULTS: ER was expressed in 30/44 (68.2%), 2/2 (100%), 2/2 (100%) of the cases of DC, LC, and PC, respectively. PR was expressed in 27/43 (63%), 2/2 (100%), 2/2 (100%) of the cases of DC, LC, and PC, correspondingly. HER2 was expressed in 13/31 (42%), 0%, and 0% of DC, LC, and PC cases, respectively. Correspondingly, E-cadherin was expressed in 11/21 (52.4%), 0%, 1/1 (100%) of the cases of DC, LC, and PC. CONCLUSIONS: Triple-negative BC and HER2+ve among Saudi women are among the higher globally reported ranges, associated with poorer response to treatment and prognosis. Luckily, only one patient was found with ER-ve PR+ve, the subtype usually associated with poorer survival outcomes. E-cadherin loss is lower among Saudi BC patients, which suggests a less rate of invasion in these patients. The current study's findings may help improve Saudi guidelines for the treatment of breast cancer.

Systemic stiffening of mouse tail tendon is related to dietary advanced glycation end products but not high-fat diet or cholesterol.

Tendon pathology is related to metabolic disease and mechanical overloading, but the effect of metabolic disease on tendon mechanics is unknown. This study investigated the effect of diet and apolipoprotein E deficiency (ApoE(-/-)) on mechanical properties and advanced glycation end product (AGE) cross-linking of non-weight-bearing mouse tail tendons. Twenty ApoE(-/-) male mice were used as a model for hypercholesterolemia along with 26 wild-type (WT) mice. One-half of the mice from each group was fed a normal diet (ND) and the other half was fed a high-fat diet (HFD) to induce obesity. All were killed at 40 wk, and tail tendon fascicles were mechanically tested to failure and analyzed for AGEs. Diets were also analyzed for AGEs. ApoE(-/-) mice displayed a 14% increase in plateau modulus compared with WT mice (P < 0.05), whereas HFD mice displayed a 13% decrease in plateau modulus (P < 0.05) and a 12% decrease in total modulus (P < 0.05) compared with ND mice. Tail tendons of HFD mice had significantly lower concentrations of AGEs [carboxymethyllysine (CML): 26%, P < 0.0001; methylglyoxal-derived hydroimidazolone 1 (MG-H1): 15%, P < 0.005; pentosidine: 13%, P < 0.0005]. The HFD had ∼44-fold lower content of CML (P < 0.01), ∼29-fold lower content of carboxyethyllysine (P < 0.005), and ∼16-fold lower content of MG-H1 (P < 0.05) compared with ND. ApoE(-/-) increased, whereas HFD decreased mouse tail tendon stiffness. Dietary AGE content may be a crucial determinant for accumulation of AGE cross-links in tendons and for tissue compliance. The results demonstrate how systemic metabolic factors may influence tendon health.

Antibacterial activity of Lawsonia inermis Linn (Henna) against Pseudomonas aeruginosa.

OBJECTIVE: To investigate the antibacterial activity of henna (Lawsonia inermis Linn) obtained from different regions of Oman against a wide array of micro-organisms. METHODS: Fresh henna samples were obtained from different regions of Oman as leaves and seeds. 100 g fresh and dry leaves and 50 g of fresh and dry seeds were separately soaked in 500 mL of ethanol for three days, respectively, with frequent agitation. The mixture was filtered, and the crude extract was collected. The crude extract was then heated, at 48 °C in a water bath to evaporate its liquid content. The dry crude henna extract was then tested for its antibacterial activity using well-diffusion antibiotic susceptibility technique. Henna extracts were investigated for their antibacterial activity at different concentrations against a wide array of different micro-organisms including a laboratory standard bacterial strain of Pseudomonas aeruginosa (NCTC 10662) (P. aeruginosa) and eleven fresh clinical isolates of P. aeruginosa obtained from patients attending the Sultan Qaboos University Hospital (SQUH). 2-Hydroxy-p-Nathoqinone-Tech (2-HPNT, MW=174.16, C10H6O3) was included as control (at 50% concentration) along with the henna samples tested. RESULTS: Henna samples demonstrated antibacterial activity against all isolates but the highest susceptibility was against P. aeruginosa with henna samples obtained from Al-sharqyia region. CONCLUSIONS: Omani henna from Al-sharqyia region demonstrates high in vitro anti-P. aeruginosa activity compared with many henna samples from different regions of Oman.

AIDS and HIV infection in Sudanese children: a clinical and epidemiological study.

HIV surveillance and screening programs were established at Khartoum Teaching Hospital (KTH) following the first identified HIV case diagnosed in a hemophiliac boy in November 1987. As of December 1995, 15 cases of symptomatic HIV infection have been observed in Sudanese children (< or = 16 years) at KTH. An HIV seroprevalence rate of 35.7% was documented in a group of 28 patients (adults and children) with various congenital coagulation defects. The postulated mode of transmission was through contaminated factor concentrate. Screening of 52,000 volunteer male blood donors (March, 1987-1989) showed an HIV-seroprevalence rate of 0.05%. Selected groups, including 1118 children admitted to KTH during the period 1985-1995, were screened for HIV infection. These included aseptic meningitis/encephalitis group (n = 52), high-risk group (n = 523), children with various chronic and malignant diseases (n = 181), and chronic blood recipients (n = 330). A group of 32 displaced homeless children who survived on the streets were also included. Overall, an HIV seroprevalence rate of 1.2% was established. Among the 15 children with symptomatic HIV infection, tuberculosis accounted for the majority of admissions (33.3%) followed by admission for recurrent infections (20.0%). Of the 13 children with nonparental mode of HIV transmission, a vertical mode was documented in 61.5%. The pattern of HIV infection in Greater Khartoum is similar to that in North Africa and the Middle East. However, the geographic influence of high endemicity in neighboring sub-Saharan countries might change it in the future.

Nutritional vitamin D deficiency rickets in Sudanese children.

Nutritional vitamin D deficiency rickets was established in 41 Sudanese children aged from 3 months to 7 years by clinical, radiological and therapeutic response supported by biochemical investigations. There were 25 boys and 16 girls, of whom 42% were infants of less than 1 year. Forty-seven per cent of rachitic children were underweight. Six infants had early rickets with no bony swellings but had other clinical features and radiological evidence of rickets. One of them, aged 3 months, presented with hypocalcaemic convulsions. Three children had icthyosis. Serum alkaline phosphatase was raised in 75%, hypophosphataemia occurred in 68% and hypocalcaemia in 54% of patients. Anaemia, mostly hypochromic, was detected in 79%. Possible causes were poor socio-economic background, inadequate dietary intake in both mothers and children, prolonged breastfeeding, prematurity, limited sun exposure and type of residence. Nutritional vitamin D deficiency rickets should be looked for in Sudanese children, especially in preterms and in those living in flats.

Pattern of congenital heart disease in Sudanese children.

One hundred and seventy nine children reporting to the paediatric cardiac clinic were studied consecutively over a 2 year period (1991-1993) using medical history, physical examination, chest x-ray, electrocardiography, echocardiography and complete haemogram. 100 (56%) of them had congenital heart disease, 70(39%) had rheumatic heart disease, four had cardiomyopathy and in five children no abnormality was detected. 58 of patients with congenital heart disease were females and 42 were males. Their age ranged between two weeks and 15 years and four months. Symptoms started in infancy in 89% of 94 symptomatic patients. The commonest symptoms were breathlessness, failure to thrive, repeated chest infections and cynosis. The other six patients were detected incidentally. Almost all types of defects were represented, the commonest being ventricular septal defect (VSD), Fallot's tetralogy, pulmonary stenosis, patent ductus arteriosus, atrioventricular septal defect and secondum atrial septal defect. Five patients with VSD were preterms. 91% of patients with VSD were symptomatic. VSD was small in one-third of patients. six patients with VSD aged 5-11 years had evidence of pulmonary hypertension, one of whom had Eisenmenger with cynosis and one found inoperable because of pulmonary vascular disease. Twenty patients had extracardiac malformations in 65% of whom more than one system was involved. 53% patients were anaemic. 47% of patients were underweight and 33% were marasmic while only 14% of controls were underweight and none of them was marasmic.

Endemic bacterial meningitis in Sudanese children: aetiology, clinical findings, treatment and short-term outcome.

During the period April 1985 to November 1986 (18 months), 196 children (of age greater than 1 month) admitted to the Children's Emergency Hospital in Khartoum, Sudan, with clinical suspicion of meningitis/meningoencephalitis were followed up prospectively. Bacterial meningitis was diagnosed by culture, direct microscopy and/or antigen-detecting assays (co-agglutination and enzyme immunoassay) in 44 infants (25 Haemophilus influenzae type b, 8 Neisseria meningitidis, 7 Streptococcus pneumoniae, 3 enterobacteria and one mixed infection), aseptic meningitis in 52, cerebral malaria in 4 and febrile convulsions in 96. The majority of cases of bacterial meningitis were boys and 57% of those in whom H. influenzae was the commonest isolate were less than 1 year old. The presenting signs and symptoms are described as well as the transient and permanent short-term sequelae. The total mortality from bacterial meningitis was 19%, permanent neurological sequelae were seen in 26% of survivors. Prospective follow-up, including audiometry, of 35 children 1-2 months after discharge showed that 11% had hemiplegia and 20% had hearing impairment. The potential impact of vaccination against invasive H. influenzae infections is discussed.

Hepatitis B and HIV in Sudan: a serosurvey for hepatitis B and human immunodeficiency virus antibodies among sexually active heterosexuals.

A serosurvey was conducted in Port Sudan and Suakin, Sudan in October and March 1987 to determine the prevalence and risk factors associated with the transmission of hepatitis B, human immunodeficiency virus type 1 (HIV-1), and syphilis among sexually active heterosexuals on the coast of Sudan. A total of 536 subjects, including 202 female prostitutes, 95 long-distance truck drivers, 103 soldiers, 72 Ethiopian refugees, and 54 Sudanese outpatients, were enrolled in the study. Seventy-eight percent (202/259) of the female study subjects were engaged in prostitution, and 57% (157/277) of the men admitted to prior sexual relations with prostitutes. Serologic markers for hepatitis B and syphilis were detected in 68% and 17% of the entire study population, respectively. In contrast, antibody to HIV-1 was detected in none of the 536 sera tested. Risk factors found to be independently predictive of hepatitis B infection by multivariate analysis included prostitution, positive serology for syphilis, and a history of anti-schistosomal therapy. The absence of HIV-1 infection among the prostitutes enrolled in this study is in marked contrast to the current AIDS epidemic in neighboring sub-Saharan countries, suggesting that HIV-1 has not been widely introduced on the coast of Sudan. The high prevalence of serologic markers to hepatitis B and syphilis, however, indicates a potential for HIV-1 in this region.

HIV-1 and hepatitis B transmission in Sudan.

A seroepidemiologic survey was conducted among 773 male soldiers living in five urban locations in Sudan to study the prevalence of and risk factors for HIV-1 and hepatitis B transmission. Twenty-eight per cent of the study population were born and raised in southern Sudan, an area bordering Kenya, Zaire and Uganda, whilst 72% of the study subjects were from northern Sudan. Seventy-eight per cent of the study population had serologic evidence of past hepatitis B infection, and 13 soldiers were confirmed positive for HIV-1 antibody. All 13 HIV-positive soldiers had recently been deployed in southern Sudan. Multivariate analysis indicated an association between living in southern Sudan and both hepatitis B (odds ratio 8.2) and HIV-1 infection (odds ratio 14). Additionally, sexual relations with prostitutes (odds ratio 1.5) and medical injections for schistosomiasis (odds ratio 2.72) were independent predictors of hepatitis B markers in this military population. The findings of this study suggest that sexual promiscuity is a risk factor for hepatitis B transmission in Sudan. They also indicate one possible route for the spread of HIV-1 from central to northern Africa.

Immunosuppression by activated human neutrophils. Dependence on the myeloperoxidase system.

An in vitro model system was used to define the mechanism of interaction between human neutrophils and lymphocytes. Blood mononuclear leukocytes were exposed to purified neutrophils in the presence of a neutrophil-activating agent (phorbol ester, lectin, or opsonized particle). The treated mononuclear cells displayed a marked decrease in both natural killer activity and mitogen-dependent DNA synthesis, but no change in viability. This functional suppression was dependent on neutrophil number, stimulus concentration, and duration of exposure. Lymphocytes were protected by addition of catalase, but not superoxide dismutase. Neutrophils defective in oxidative metabolism (chronic granulomatous disease) failed to suppress lymphocyte function unless an H2O2-generating system, glucose oxidase plus glucose, was added. The patients' neutrophils provided a factor, possibly myeloperoxidase, which interacted with the glucose oxidase system. The immunosuppressive effect of normal neutrophils was diminished when chloride was omitted from the cultures and was enhanced when chloride was replaced by iodide. Myeloperoxidase-deficient neutrophils were partially defective in suppressing lymphocytes and this was corrected by addition of purified myeloperoxidase. Paradoxically, azide caused enhancement of suppression that depended on the neutrophil oxidative burst, but not on myeloperoxidase and was mediated at least in part by an effect of azide on the target mononuclear leukocytes. These data indicate that suppression of lymphocyte function by activated neutrophils is mediated by the secretion of myeloperoxidase and H2O2 that react with halides to form immunosuppressive products. Moreover, the mononuclear leukocytes contain an azide-sensitive factor, probably catalase, which provides partial protection against injury by neutrophil products. These dynamic interactions may be important local determinants of the immune response.

Non-A, non-B hepatitis in Omdurman, Sudan.

One-hundred nineteen patients (cases) at least 13 years of age with acute hepatitis were studied to determine the viral etiology of acute hepatitis in Omdurman, Sudan. Ninety-eight control subjects (controls) were also evaluated to determine the risk factors associated with the development of clinical disease. Acute hepatitis non-A, non-B was diagnosed in 88 cases (73.9%), hepatitis B in 15 cases (12.6%), delta infection in 15 (12.6%), and hepatitis A in just one patient (0.8%). A higher percentage of hepatitis B cases had received a parenteral injection for medical therapy during the previous 6 months than control subjects (26.7% vs 4.1%, p less than 0.05). The data in this study indicate that hepatitis non-a, non-B may be the major cause of acute hepatitis in adults in this area of Sudan. The suggested association of parenteral therapy with the transmission of hepatitis B could have important implications for the spread of other parenterally-transmitted diseases.

Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide: differential susceptibility of human lymphocyte functions.

The coexistence of activated polymorphonuclear leukocytes and lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. To test this hypothesis, we examined the effects of neutrophil myeloperoxidase and H2O2 on lymphocytes. Human peripheral blood mononuclear leukocytes were exposed to myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase), and a halide, and were then tested for functional activities. Natural killer activity against K562 cells, lymphocyte proliferation in response to mitogens, and generation of immunoglobulin-secreting cells were all susceptible to oxidative injury by myeloperoxidase and H2O2. The degree as well as the mechanism of suppression was dependent on the glucose oxidase concentration (i.e., the rate of H2O2 delivery). At low H2O2 flux, myeloperoxidase was essential for induction of lymphocyte suppression; as the rate of H2O2 generation increased, suppression became myeloperoxidase-independent and was mediated by H2O2 alone. Various lymphocyte functions were differentially susceptible to oxidative injury by myeloperoxidase and H2O2. The proliferative response to poke-weed mitogen was the least sensitive, whereas antibody formation was the most sensitive. Proliferative responses to concanavalin A and phytohemagglutinin as well as natural killer activity displayed intermediate degrees of susceptibility. In all assays, lymphocyte viability was greater than 90%. Removal of monocytes from mononuclear leukocytes by adherence to glass increased susceptibility of lymphocytes to oxidative injury. Monocytes in proportions within the range present in peripheral blood mononuclear leukocytes protected lymphocyte functions against oxidative injury by myeloperoxidase and H2O2. This study demonstrates a differential susceptibility of various immune functions to oxidative injury by the neutrophil products myeloperoxidase and H2O2, and shows, in addition, that monocytes can modulate these interactions.

Down-regulation of human natural killer activity against tumors by the neutrophil myeloperoxidase system and hydrogen peroxide.

There is growing evidence that natural killer (NK) cells play an important role in immune surveillance against tumors and certain infections. The coexistence of activated neutrophils with lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. We examined the susceptibility of lymphocyte NK activity to oxidative injury by the neutrophil myeloperoxidase (MPO) system and H2O2 with the use of a cellfree model system. Exposure of human mononuclear leukocytes (MNL) to MPO, an H2O2-generating system (glucose + glucose oxidase), and a halide (C1- or I-) resulted in marked suppression of MNL-NK activity, as measured by 51Cr release from K562 tumor targets (p less than 0.001). This suppression was dependent on the presence and activity of each system component and was blocked by azide and catalase, but not by heated catalase. In spite of the marked functional suppression of NK activity, MNL viability was more than 95% and target binding frequency was not affected. NK suppression was reversible after 24 hr in culture. The mechanism of suppression was dependent on the amount and rate of H2O2 delivered, and on MNL number. MPO was essential when H2O2 flux was low or when MNL numbers were high. As H2O2 flux increased or MNL numbers decreased, NK suppression gradually became MPO-independent and was mediated by H2O2 alone. The ability of the MPO system to compromise lymphocyte NK function may explain the in vitro inhibition of NK activity of mixed cell populations by the tumor promoter phorbol esters, because these agents are potent stimulants for neutrophil secretion of MPO and H2O2. This study may also provide a possible mechanism for the reported in situ NK activity suppression by adherent phagocytic cells during carcinogenesis in both humans and animals.

Proteinuria in Sudanese children.

One thousand, eight hundred and forty-six apparently healthy nursery and school children living in the Khartoum area and belonging to different socio-economic classes were studied. Nine hundred and thirty-seven were boys, 909 girls. Their ages ranged from three to 16 years. N-multistix strips were used to test for proteinuria and haematuria, the former being also checked by the sulphosalicylic acid test. Children with proteinuria of 1+ or more were further investigated by examining their urinary sediment for abnormal deposits and by testing for orthostatic proteinuria using day and night specimens of urine with specific gravity of 1.018 or more. Children who had no proteins on orthostatic testing were rescreened for proteinuria 10-14 days after the initial screening. The prevalence rate for proteinuria was 7.2% with no significant difference between boys and girls. In both sexes the prevalence rate increased significantly with age but was not influenced by the socio-economic status. Of the children with proteinuria, haematuria occurred in 27% and abnormal urinary deposits in 14.8%. Orthostatic testing showed a negative result for proteins in 44%, orthostatic proteinuria in 40%, of whom a third had either abnormal urinary sediments or haematuria, and continuous proteinuria in 15.6% of whom the majority had abnormal deposits.

Myeloperoxidase-catalyzed inactivation of alpha 1-protease inhibitor by human neutrophils.

We have examined the effect of the myeloperoxidase-hydrogen peroxide-halide system and of activated human neutrophils on the ability of serum alpha 1-protease inhibitor (alpha 1-PI) to bind and inhibit porcine pancreatic elastase. Exposure to the isolated myeloperoxidase system resulted in nearly complete inactivation of alpha 1-PI. Inactivation was rapid (10 to 20 s); required active myeloperoxidase, micromolar concentrations of H2O2 (or glucose oxidase as a peroxide generator), and a halide cofactor (Cl- or I-); and was blocked by azide, cyanide, and catalase. Intact neutrophils similarly inactivated alpha 1-PI over the course of 5 to 10 min. Inactivation required the neutrophils, a halide (Cl-), and a phorbol ester to activate secretory and metabolic activity. It was inhibited by azide, cyanide, and catalase, but not by superoxide dismutase. Neutrophils with absent myeloperoxidase or impaired oxidative metabolism (chronic granulomatous disease) failed to inactivate alpha 1-PI, and these defects were specifically corrected by the addition of myeloperoxidase or H2O2, respectively. Thus, stimulated neutrophils secrete myeloperoxidase and H2O2 which combine with a halide to inactivate alpha 1-PI. We suggest that leukocyte-derived oxidants, especially the myeloperoxidase system, may contribute to proteolytic tissue injury, for example in elastase-induced pulmonary emphysema, by oxidative inactivation of protective antiproteases.