Interplay of interleukins (IL6, IL10) and 25 hydroxycholecalciferol in asthmatic subjects with chronic post-COVID condition (PCC).

The study aimed to compare and correlate serum levels of IL-6, 10, and 25-hydroxycholecalciferol in individuals with asthma with and without post-COVID condition (PCC). The study was designed to investigate the inflammatory response and serum 25-hydroxycholecalciferol status in asthmatics with and without PCC. A cross-sectional study of 252 subjects (128 asthmatics and 124 non-asthmatic subjects) was carried out. Interleukins and 25-hydroxycholecalciferol levels were estimated on ELISA. The principle findings were that IL-6 and 25-hydroxycholecalciferol levels were significantly increased (p<0.001), while IL-10 levels were non-significant in asthmatics with PCC compared to those without PCC. However, 25-hydroxycholecalciferol levels were significantly increased, but no significant change was observed in IL-6, and IL-10 levels in non-asthmatics with and without chronic PCC. A significant positive correlation (r = 0.258) was found between 25-hydroxycholecalciferol and IL-6 but a significant negative correlation (r = -0.227) with IL-10 in asthmatics with PCC. Similarly, a significant negative correlation (r = -0.285) was found between 25-hydroxycholecalciferol and IL-10 but was non-significant with IL-6 in asthmatics without PCC. The correlation of 25-hydroxycholecalciferol with IL-10 was significant (0.683), but IL-6 was non-significant in non-asthmatics with PCC. Multiple regression analysis showed that age, IL-6, gender, and PCC were significantly related in adjusted values to 25-hydroxycholecalciferol. This study sheds light on the complex liaison between 25-hydroxycholecalciferol levels and inflammatory responses in asthmatics, especially those with PCC. The findings suggest that although asthmatics with PCC maintain sufficient levels of 25-hydroxycholecalciferol, they show a substantial increase in the proinflammatory response. This suggests that PCC exacerbates the pro-inflammatory response in asthma. Moreover, the study reveals that asthmatics, whether with or without PCC, display a negative correlation between 25-hydroxycholecalciferol and the anti-inflammatory response. This emphasizes the main influence of asthma on the overall inflammatory response. These findings reveal a complex interplay between vitamin D levels and inflammatory mediators in asthmatic individuals with and without PCC.

Insulin-like growth factor-1 gene polymorphism in rheumatoid arthritis patients.

OBJECTIVES: Insulin-like growth factor-1 (IGF-1) regulates several biological functions, and low plasma levels of IGF-1 are known to contribute towards the pathogenesis of rheumatoid arthritis (RA). In view of the biological significance of IGF-1, we investigated the association of RA with the polymorphism of a 192-bp allele which is cytosine-adenosine repeat located 1 kb upstream from the IGF-1 gene transcription site and is known to regulate serum IGF-1 levels. METHODS: Blood samples were collected from 52 healthy controls (HC) and 68 RA patients to measure the levels of IGF-1 and to isolate genomic DNA. Polymorphism of the IGF-1 gene was examined using polymerase chain reaction (PCR). Disease severity, duration, and activity were recorded for all RA patients. RESULTS: We observed that 97% of all the subjects who participated in this study showed the presence of a 192-bp allele of the IGF-1 gene. All healthy controls exhibited the presence of 192-bp wild-type allele. All non-carriers of the 192-bp allele were Arabs and had RA. Gender correlated significantly with allele frequencies as 14% of the male and only 2% of the female RA patients were non-carriers of 192-bp allele. Plasma IGF-1 levels were significantly lower (p < 0.01) in RA patients compared to HC, and all RA patients who were non-carriers of the 192-bp allele had a significantly high disease activity score. No correlation was found between the duration of RA and the presence or absence of this allele. CONCLUSIONS: This study suggests a possible association of the IGF-1 gene polymorphism with developing RA, particularly in males as non-carriers of the 192-bp allele.

Efficacy and safety of infliximab in active SLE: a pilot study.

Tumour necrosis factor-alpha (TNF-alpha) plays a major role in propagating the inflammatory processes responsible for tissue damage in systemic lupus erythematosus (SLE) and is overexpressed both systemically and locally in this disease. Hence, this pilot study was carried out to assess the safety and efficacy of TNF blockade in patients with active SLE. A total of 46 individuals (27 patients with active SLE and 19 healthy control volunteers) were the subjects of this study. Nine patients with SLE were allocated to treatment arm and 18 were allocated to control arm. In addition to conventional treatment, treatment arm received infliximab infusions 3 mg/kg body weight at 0, 2, 6 weeks and then q 8 weeks for a total of 24 weeks, that is, a total of five doses. Patients were closely monitored for infection. Clinical, laboratory and treatment data were entered into a pre-designed proforma. Health status (SF-36), patient global assessment (PGA) of disease activity, disease activity scores by SLEDAI and organ damage by SLICC/ACR-DI (American College Rheumatology) were measured at baseline and end of the study. Relevant immunological studies included serum levels of TNF-alpha and soluble TNF receptors-1 (p55 srTNF-alpha) and -2 (p75 srTNF-alpha), C3 and C4 complement levels, anti-dsDNA antibody titres (IgM, IgG and IgA isotypes), anti-cardiolipin titres (IgM, IgG and IgA isotypes) and anti-beta2GPI (Glycoprotein I) antibody titres (IgM, IgG and IgA isotypes). Four patients from treatment arm dropped out due to infliximab infusion reaction and 12 patients dropped out from the control arm. The treatment group showed significantly greater improvement in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Improvements in several SF-36 subscales, PGA and VAS-Fatigue (Visual Analogue Scale) were also greater in the treatment group but did not achieve statistical significance. The mean levels of TNF-alpha, soluble TNF receptors-1 (p55 srTNF-alpha) and -2 (p75 srTNF-alpha) were higher in the SLE group compared with the healthy controls but did not change significantly over the study period. We did not face any safety issues with infliximab in this study. In view of improvement in several SLE parameters and good safety profile of infliximab, anti-TNF-alpha therapy is an interesting candidate approach for treating SLE.

Henoch-Schönlein's purpura in adults versus children/adolescents: A comparative study.

OBJECTIVE: To assess the possible differences in etiological and clinical factors between children/adolescents (< or = 20 years) and adults (> 20 years) with Henoch-Schonlein purpura (HSP). METHODS: A retrospective-cum-prospective study of consecutive patients with HSP who presented to our teaching hospital over 5 years. Patients were classified as having HSP according to the criteria proposed by Michel et al and the ACR criteria. RESULTS: 102 patients (43 of all patients being male and 59 female) were classified as having HSP; 20 of the patients were adults (mean age 32.1 +/- 11.7 years) and 82 were children/adolescents (mean age 6.2 +/- 2.6 years). We were unable to identify any precipitating event in 40% of the adults and 37% of the children/adolescents. The frequency of previous drug treatment and of previous upper respiratory tract infection was similar in both groups. At symptom onset, palpable purpura was the chief clinical manifestation in both groups. However, renal involvement, in all its aspects, was more frequent and severe in adults. Adults also had a higher frequency of diarrhoea (with or without occult blood) and leucocytosis, but a lower frequency of thrombocytosis. The frequency of joint manifestations, nausea, vomiting, malena/hematochezia and intussuseption was equal in both groups. Adults required more aggressive therapy, and had a longer hospital stay (10.2 vs. 4.3 days). The outcome was relatively worse in adults, with complete recovery in 18 adults (90%) compared to 81 children/adolescents (98.8%) after a mean +/- SD follow up of 2.8 +/- 1.7 and 2.4 +/- 1.3 years, respectively. CONCLUSION: In adulthood, HSP is a more severe clinical syndrome, with a higher frequency of diarrhoea and renal involvement. Adults also require aggressive treatment more frequently and have a longer hospital stay.

Occurrence of overlooked zoonotic tuberculosis: detection of Mycobacterium bovis in human cerebrospinal fluid.

The paucibacillary nature of the cerebrospinal fluid (CSF) has been a major obstacle in the diagnosis of human tuberculous meningitis (TBM). This study shows that with molecular techniques direct precise determination to the species level of mycobacterial pathogens can be made. The present report describes the utility of a nested PCR (N-PCR) assay (A. Mishra, A. Singhal, D. S. Chauhan, V. M. Katoch, K. Srivastava, S. S. Thakral, S. S. Bharadwaj, V. Sreenivas, and H. K. Prasad, J. Clin. Microbiol. 43:5670-5678, 2005) in detecting M. tuberculosis and M. bovis in human CSF. In 2.8% (6/212) of the samples, M. tuberculosis was detected, and in 17% (36/212), M. bovis was detected. Mixed infection was observed in 22 samples. Comparative analysis of clinical diagnosis, smear microscopy, and N-PCR in 69 patients (TBM, 25; non-TBM, 44) showed that the sensitivity of N-PCR (61.5%) was greater than that of smear microscopy (38.4%). Determination to the species level is important from the viewpoint of determining the prevalence of these mycobacteria in a community and would influence strategies currently adopted for the prevention of tuberculosis.

Ankylosing spondylitis and undifferentiated spondyloarthritis in Kuwait: a comparison between Arabs and South Asians.

The objectives of this study were to describe and compare the clinical characteristics of ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (USpA) in Middle East Arab (MEA) and South Asian (SA) patients diagnosed in our unit. Fifty-eight consecutive patients diagnosed with SpA were studied after classifying them into MEA and SA. They were further classified as per disease diagnosis. Excluding three patients with miscellaneous ethnicity, there were 29 MEA and 26 SA patients. Seventy-two percent of MEA patients were males (vs 92% of SA patients). Of the 29 patients with MEA ethnicity, 17 had AS and 9 had USpA. Of the 26 patients with SA ethnicity, 10 had AS and 14 had USpA. Fifty-nine percent of MEA patients had AS (vs 39% of SA patients). Mean age at onset in AS patients was similar in the two ethnic groups. However, in patients with USpA, mean age at onset was somewhat lower at 21.8 years in the MEA group compared with 29.4 years in the SA group. Family history in first-degree relatives was significantly more common in MEA patients. Weight loss, inflammatory spinal pain, gluteal pain, and enthesopathy were equally common in both ethnic groups. Knee, ankle, and metatarsophalangeal joint involvement was less common in MEA patients. There were no significant differences in the occurrence of syndesmophytes, bamboo spine, and sacroiliitis in the two ethnic groups. HLA-B27 positivity rates in MEA patients were 87% for AS and 67% for USpA compared to 75 and 71%, respectively, in SA patients. It is concluded that some significant new findings have arisen from this study: the majority of MEA patients presented with AS, whereas the majority of SA patients had a picture of USpA. Family history was more common in MEA patients. Peripheral arthritis was less common in MEA patients. Worldwide, this is the first study to show that there are significant differences in the clinical expression of the various SpA in MEA patients compared to SA patients.

First report of leprosy presenting as acute polyarthritis in the setting of type I downgrading lepra reaction.

Leprosy is a rare cause of acute polyarthritis. We describe the occurrence of oedema of the hands and feet and acute polyarthritis in the setting of type I (downgrading) lepra reaction in an untreated patient with borderline leprosy. This case report further expands the range of articular manifestations that can occur in leprosy.

First report of supraventricular tachycardia after intravenous pulse methylprednisolone therapy, with a brief review of the literature.

The occurrence of supraventricular tachycardia after high-dose intravenous methylprednisolone pulse therapy (HIVMPT) in a patient with active rheumatoid arthritis is described for the first time. This case report further expands the range of arrhythmias that can occur with HIVMPT. Other arrhythmias previously reported to occur after HIVMPT include atrial fibrillation, atrial flutter, junctional rhythm, and ventricular tachycardia. To the best of our knowledge, supraventricular tachycardia has not been reported previously, although severe bradycardia, hypotension, asystole, cardiovascular collapse, and sudden death have been documented. A review of the literature indicates that these case reports not withstanding, HIVMPT is generally safe, and cardiovascular toxicity is rare. However, close supervision with repeated measurements of blood pressure, electrocardiogram, and blood electrolytes is mandatory during and immediately after HIVMPT, especially for patients with pre-existing cardiovascular disease, and the lowest effective dose of methylprednisolone should be infused at a slow rate.

Comparison of CD4 and CD8 lymphocyte counts in HIV-negative pulmonary TB patients with those in normal blood donors and the effect of antitubercular treatment: hospital-based flow cytometric study.

BACKGROUND: This study was designed to flow cytometrically determine baseline and sequential values of CD4 and CD8 lymphocyte subsets in patients without the human immunodeficiency virus and with pulmonary tuberculosis (TB) and to correlate these values with those obtained from normal male blood donors and with the radiologic extent of disease and response to therapy. METHODS: We studied 39 male patients without the human immunodeficiency virus and with sputum positive for pulmonary TB who had been admitted to Military Hospital (Cardiothoracic Center) in Pune, India. Clinical, laboratory, and radiologic evaluations of these patients were done. Hematologic parameters were assessed by an automated hematology cell counter (AcT*Diff, Coulter), and T-cell subsets (CD4 and CD8) were determined flow cytometrically (EPICS-XL, Coulter). RESULTS: CD4 counts and percentages of CD4 were significantly lower, but CD8 values were normal, in patients with pulmonary TB when compared with values obtained in normal blood donors. The CD4/CD8 ratio was significantly lower in patients with TB. The CD4 counts normalized with antitubercular treatment. The radiologic extent of disease did not correlate well with the immune parameters studied. CONCLUSIONS: TB is a reversible cause of CD4 lymphocytopenia and is associated with normal numbers of CD8 cells. The radiologic extent of disease does not seem to determine the immune response.

Left gluteal focal myositis in a patient with signet ring adenocarcinoma of the stomach: not a paraneoplastic phenomenon.

Focal myositis, the much rarer clinical and pathological variant of polymyositis, is generally a benign inflammatory pseudotumor of skeletal muscle Thus far, only three cases have been reported in association with a neoplasm. We now describe a fourth case of localized gluteal myositis seen in a case of signet ring adenocarcinoma of the stomach occurring not as a paraneoplastic syndrome, as in the previously reported three cases, but as an immunoinflammatory response around metastatic cell foci in both the involved muscles and local lymphatics.

Normal values of CD4 and CD8 lymphocyte subsets in healthy indian adults and the effects of sex, age, ethnicity, and smoking.

BACKGROUND: Information on lymphocyte populations (T, B, and natural killer cells) and subpopulations (CD4 and CD8) in India is generally lacking. Measurement of T-cell subsets is important in India for evaluating disease stage and progression in individuals with the human immunodeficiency virus (HIV). Hence, this study was conducted to provide normal ranges of absolute and percentage values of CD4 and CD8 T-lymphocyte subsets and the ratio of CD4 to CD8 in normal Indian adults. METHODS: Flow cytometric analysis (EPICS-XL) was used to determine the range of T-lymphocyte subpopulations in normal Indian blood donors at Command Hospital and the Armed Forces Medical College, Pune, India. The reference population consisted of 94 healthy HIV-seronegative blood donors. T-lymphocyte subsets were analyzed with two-color immunophenotyping of peripheral blood lymphocytes with the use of a lysed whole-blood technique and enumerated. RESULTS: For normal values of various blood components, we found mean values of 2114 cells/microl for total lymphocytes, 865 cells/microl (40.2%) for CD4(+) lymphocytes, 552 cells/microl (31.3%) for CD8(+) lymphocytes, and 1.7 for the CD4:CD8 ratio. The 95% confidence intervals for the same parameters were 1115-4009 cells/microl, 430-1740 cells/microl (30.75-49.60%), 218-1396 cells/microl (20.06-42.52%), and 0.39-3.02 respectively. Females had significantly higher CD4 counts (P < 0.05), percentage of CD4 lymphocytes (P < 0.01), and CD4:CD8 ratio (P < 0.01). Males had a significantly higher percentage of CD8 lymphocytes (P < 0.01). They also had higher CD8 counts that did not reach significance. Age, ethnicity (Dravidian versus Aryan), smoking, alcohol consumption, and the interval between drawing the blood sample and its analysis were factors that did not produce statistically significant differences in the T-cell subsets studied. CONCLUSIONS: When compared with other published series, the CD4 and CD8 values in healthy Indians were no different from those reported in the West. These observations have important clinical implications for the use of T-lymphocyte subset measurements in India, especially in the management of HIV infection. The normal ranges established by this study can be used as a reference for decisions made in clinical practice.

Analysis of the clinical profile, autoimmune phenomena and T cell subsets (CD4 and CD8) in Takayasu's arteritis: a hospital-based study.

OBJECTIVE: To evaluate clinical and immunological abnormalities in patients with Takayasu's arteritis (TA) from India, with particular reference to autoimmune perturbations and abnormalities in T cell subsets (CD4 and CD8 cells). METHODS: 16 consecutive patients with TA (11 females and 5 males) underwent clinical and laboratory evaluation inclusive of flow cytometric analysis of T cell subsets (CD4 and CD8). A control population of 94 age- and sex-matched blood donors was used to determine the normal T cell subsets. Student's t-test was used to compare the means. RESULTS: The mean age at onset was 23.4 + 2.3 yrs. Common symptoms observed were headache, limb claudication, abdominal pain and visual disturbance/blackout. Common clinical signs observed included reduced arterial pulsations, bruits, and a BP difference > 10 mm Hg in the upper limbs. Systemic hypertension was documented in 12 patients. The mean absolute lymphocyte count in the patients was 2289/mm3. The mean CD4 count and CD4% were 1003 and 41 respectively; the mean CD8 count and CD8% were 755 and 34, respectively; and the mean CD4/8 ratio was 1.41. The patients had statistically significantly higher CD8 but not CD4 T cell values than controls. IgG and IgM immunoglobulin levels were increased. The mean multi-test CMI score in patients using CMI multi-test device of Pasteur Merieux was 14.6 mm. Two patients had an anergic response, 4 a partial response (1-13 mm), and 6 a full response of > 13 mm. Four patients hyper-responded with a score of > 20 mm. ANCA was positive in 2 patients. ANA was positive in 3 patients. IgG anticardiolipin was positive in 12 patients and IgM in 3; overall 12 patients were anticardiolipin positive by ELISA. Anti-beta 2GPI of the IgG variety was found to be positive in 3 patients and IgM in 2 patients; overall 3 patients being positive for the same. Nine of the patients with active disease were started on a combination of moderate dose prednisolone (20-40 mg once daily) along with weekly oral methotrexate (7.5-15.0 mg). Surgical intervention was required in 6 patients. CONCLUSION: This study found an increase in CD8 positive T cell subsets, increased IgG and IgM immunoglobulin levels, and the presence of autoantibodies including ANA, ANCA, anticardiolipin and anti-beta 2GPI antibodies in TA patients. TA may be an autoimmune disorder with T cell aberrations. The relationship with antiphospholipid antibodies and anti-beta 2GPI needs to be explored and confirmed by other larger studies. The strikingly positive responses to tuberculin, as well as the multi-test CMI also indicate exaggerated T cell responses and cell mediated immunity in Takayasu's arteritis. Immunosuppressive therapy was successful in controlling disease activity in the majority, but surgery was needed for irreversible stenotic lesions.

LUPUS NEPHRITIS-A CRITICAL ANALYSIS OF 17 PATIENTS.

Over a 3 year period from June 94 to June 97, out of 28 patients of systemic lupus, 17 were diagnosed as renal lupus. Demographic data showed 12 females and 5 males, mean age being 32.2 years (range 12 to 54 years). Mean time gap between presentation and definitive diagnosis was 32.4 days (7 days to 5 years). 2 patients (11.76%) presented renal lupus, one (5.88%) with acute interstitial lung disease and the remaining had the usual systemic manifestations of lupus. Anti dsDNA antibodies were positive in all patients while ANA was negative in 3 cases. Renal involvement consisted of rapidly progressive glomerulonephritis in 2 patients (11.76%), nephrotic syndrome in 4 (23.52%) and non nephrotic range proteinuria in 11 (64.70%) patients. Mean serum creatinine at presentation was 2.4mg/dl (0.8mg/dl to 8.9 mg/dl). Three patients were dialysis dependent. Renal histology on light microscopy comprised of class II lesions in one (5.88%), class III in 4 (23.52%), class IV in 11 (64.70%-including one with crescents) and class V in one (5.88%) patient. All patients with advanced class III/IV lesions were treated with corticosteroids and cyclophosphamide pulses. Except one patient who died of pyopericardium all others improved and their serum creatinine stabilised around 2.3 mg/dl (0.8 to 4.6 mg/dl). The study highlights the importance of early diagnosis and aggressive management in this potentially treatable disease.

SONOGRAPHY : A VALUABLE MODALITY IN EVALUATION OF CHRONIC NON-TRAUMATIC DISORDERS OF THE SHOULDER JOINT.

Chronic non-traumatic shoulder pain may be due to arthralgia, shoulder myalgia, glenohumeral synovitis, adhesive capsulitis, or degenerative joint disease. Clinical skills and routine radiography may not be adequate to establish the diagnosis. This study was designed to assess the role of sonography in such a setting. Twenty-six consecutive patients attending the clinical immunology outpatient department for chronic shoulder pain were evaluated. Based on our findings, we have described 4 distinct sonographic patterns. Pattern 1 consisted of the normal sonographic appearance with semicircular smooth humeral head profile parallel to which was an echo-free synovial space measuring 1-2 mm. This pattern indicated shoulder arthralgia or myalgia without intrinsic shoulder joint disease. Pattern 2 consisted of reduction in the echo-free space indicative of adhesive capsulitis. Pattern 3 consisted of uniform increase in this space, thus indicating active synovial inflammation with effusion. Pattern 4 showed irregularity of the humeral head with reduction in the gleno-humeral joint space and loss of parallelism between the humeral head and the surrounding gleno-humeral synovial space. This last pattern indicated advanced deformed inflammatory or degenerative arthritis. It is concluded that these 4 sonographic patterns will be of considerable help in pinpointing the diagnosis in cases of chronic non-trumatic shoulder pain.

BETA-2-MICROGLOBULIN LEVELS IN HUMAN-IMMUNODEFICIENCY VIRUS INFECTED SUBJECTS.

We studied beta-2 microglobulin (ß-2M) levels in 44 HIV infected subjects belonging to 3 clinical stages as well as in 25 healthy controls. The method used was a competition enzyme immunoassay. In this study, levels of ß2-M were measured in two groups of HIV infected individuals, the asymptomatic and those with progressive and advanced disease, in order to affirm its role as a surrogate prognostic marker. It was found that mean ß-2M levels were 1.28 mg/L in the controls (normal range 0-2.4 mg/L), 11.41 mg/L in the HIV infected subjects, 2.69 mg/L in the asymptomatic HIV infected, 12.14 mg/L in those with persistent generalized lymphadenopathy (PGL) and 39.29 mg/L in the patients with acquired immunodeficiency syndrome. It was concluded that ß-2M levels were significantly higher in the HIV infected as compared to the controls. Further, the levels were much higher in the HIV infected with progressive diseasc/PGL and highest in those who had developed AIDS. ß-2M is an important surrogate serological marker useful in prognostication of disease process in the HIV infected. Advantages of measuring ß-2M levels over p24 antigen detection and CD4 counts were highlighted.

AIDS AWARENESS IN PATIENTS ATTENDING THE MEDICAL OUTPATIENT DEPARTMENT OF A PUNE HOSPITAL.

A bilingual questionnaire was administered to 400 out-patients to assess their acquired immunodeficiency syndrome (AIDS) awareness. Results were analyzed and three scores, namely educational score (%ES), media score (%MS) and AIDS awareness score (%AAS) were devised to give per cent values to these parameters. Only 49 per cent of the males and 26 per cent of the females had studied beyond Class 10. As many as 103 (25.8%) subjects had never heard of AIDS. The remaining 297 patients knew a fair amount but misconceptions were very common. The %AAS was over 80 per cent in students and in civil servants, around 70 per cent in government servants and business persons and around 60 per cent in house wives. It was higher in those from urban backgrounds and in males. The education and media scores of those ignorant of AIDS were poor compared to those aware of AIDS. Risk factors for ignorance were poor educational levels, low exposure to public media and female gender. A very basic take-off level is therefore required when physicians discuss AIDS related issues with their patients.